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In electrokinetic remediation (EKR), the sedimentary dissolved organic matter (DOM) could impede remediation by scavenging reactive species and generating unintended byproducts. Yet its transformation and mechanisms remained largely unknown. This study conducted molecular-level characterization of the water-extractable DOM (WEOM) in EKR using negative-ion electrospray ionization coupled to 21 tesla Fourier transform ion cyclotron resonance mass spectrometry (21 T FT-ICR MS). The results suggested that ∼55 % of the ∼7,000 WEOM compounds identified were reactive, and EKR lowered their diversity, molecular weight distribution, and double-bond equivalent (DBE) through a combination of electrochemical and microbial redox reactions. Heteroatom-containing WEOM (CHON and CHOS) were abundant (∼ 35% of the total WEOM), with CHOS generally being more reactive than CHON. Low electric potential (1 V/cm) promoted the growth of dealkylation and desulfurization bacteria, and led to anodic CO 2 mineralization, anodic cleavage of -SO and -SO 3 , and cathodic cleavage of -SH 2 ; high electric potential (2 V/cm) only enriched desulfurization bacteria, and differently, led to anodic oxygenation and cathodic hydrogenation of unsaturated and phenolic compounds, in addition to cathodic cleavage of -SH 2 . The long-term impact of these changes on soil quality and nitrogen-sulfur-carbon flux may be need to studied to identify unknown risks and new applications of EKR., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Citronellol (CT) is a monoterpene alcohol present in the essential oil of plants of the genus Cymbopogon and exhibits diverse pharmacological activities. The aim of the current study was to investigate the hepatoprotective potential of CT against ethanol-induced toxicity in HepG2 cell lines. Silymarin (SIL) was used as a standard drug. MTT, crystal violet assay, DAPI, and PI staining were carried out to assess the effect of ethanol and CT on cell viability. RT-PCR determined the molecular mechanisms of hepatoprotective action of CT. CT ameliorated cell viability and restricted ethanol-induced cell death. DAPI and PI staining showed distinct differences in cell number and morphology. Less cell viability was observed in the diseased group obviously from strong PI staining when compared to the CT- and SIL-treated group. Moreover, CT showed downregulation of interleukin (IL-6), transforming growth factor-beta 1 (TGF-β1), collagen type 1 A 1 (COL1A1), matrix metalloproteinase-1 (MMP-1), tissue inhibitor of metalloproteinase-1 (TIMP-1) and glutathione peroxidase-7 (GPX-7) levels. Molecular docking studies supported the biochemical findings. It is concluded that the cytoprotective activity of CT against ethanol-induced toxicity might be explained by its anti-inflammatory, immunomodulatory, and collagen-regulating effects., Competing Interests: Conflict of interest: Authors state no conflict of interest., (© 2024 the author(s), published by De Gruyter.)

In the current study, new pyrazolo[3,4-b]pyridine esters, hydrazides, and Schiff bases have been synthesized starting from 3-methyl-1-phenyl-1H-pyrazol-5-amine. The first step involved solvent-free synthesis of pyrazolo[3,4-b]pyridine-6-carboxylate derivatives (2a-d) with 55%-70% yield in the minimum time frame compared with the conventional refluxing method, which was followed by the synthesis of corresponding hydrazides (3a-d) and hydrazones (4a-e). The structures of the synthesized derivatives were confirmed using element analysis, FT-IR, 1 H NMR, 13 C NMR, and LC-MS techniques. Synthesized hydrazides (3a-d) and hydrazones (4a-e) were also tested for their in-vitro antidiabetic activity and found that all the compounds exhibited significant antidiabetic activity, while 3c (IC 50  = 9.6 ± 0.5 μM) among the hydrazides and 4c (IC 50  = 13.9 ± 0.7 μM) among the hydrazones were found to be more active in comparison to other synthesized derivatives. These in-vitro results were further validated via docking studies against the α-amylase enzyme using the reference drug acarbose (200.1 ± 10.0 μM). The results were greatly in agreement with their in-vitro studies and these derivatives can be encouraging candidates for further in-vivo studies in mice models., (© 2024 Wiley Periodicals LLC.)

Glyphosate, the most widely used herbicide globally, is accumulating in the environment and poses significant potential eco- and bio-toxicity risks. While natural attenuation of glyphosate has been reported, the efficacy varies considerably and the dominant metabolite, aminomethylphosphonic acid (AMPA), is potentially more persistent and toxic. This study investigated the bioelectrochemical system (BES) for glyphosate degradation under anaerobic, reductive conditions. Atomistic simulations using density functional theory (DFT) predicted increased thermodynamic favorability for the non-dominant C-P lyase degradation pathway under external charge, which suppressed AMPA production. Experimental results confirmed that cathodic poised potential (-0.4 V vs. Ag/AgCl) enhanced glyphosate degradation (75 % in BES vs. ∼40 % in the control conditions after 37 days), and lowered the AMPA yield (0.52 mol AMPA yield per mol glyphosate removed in BES vs. 0.77-0.86 mol mol -1 in the control conditions). Geobacter lovleyi was likely the active species driving the C-P lyase pathway, as evidenced by the increase of its relative abundance, the upregulation of its extracellular electron transfer genes (most notably mtr) and the up-regulation of its phnJ and hcp genes (encoding C-P layse and hydroxylamine reductase respectively)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

This study aims to design and optimize ondansetron (OND) gastro-retentive floating minitablets for better and prolonged control of postoperative nausea and vomiting (PONV) with improved patient compliance. Minitablets were directly compressed and encapsulated in a size 2 capsule shell with an overall dose of 24 mg. Central composite design (CCD) was applied keeping one cellulose ether derivative HPMC K15M and Carbopol 971 as variable and used as swelling and rate retarding agents. The other cellulose derivative i.e. sodium carboxymethyl cellulose, along with mannitol, sodium bicarbonate, and talc, were used in fixed quantities. The floating lag time, total floating time, swelling index, in-vitro drug release, and zero-order (RSQ value), were critical quality parameters. The optimized formulation (F pred ) was evaluated for all critical parameters, along with surface morphology, thermal stability, chemical interaction, and accelerated stability. The in silico PBPK modeling was applied to compare the bioavailability of F pred with reference OND immediate-release tablets. The numerical optimization model predicted >90 % drug release with zero-order at 12 h. In silico PBPK modeling revealed comparable relative bioavailability of F pred with the reference formulation. The gastroretentive floating minitablets of OND were successfully designed for prolonged emesis control in patients receiving chemotherapeutic agents., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and objectives : Pre-eclampsia (PE) is a pregnancy-specific condition characterized by significant health risks for pregnant women worldwide due to its status as a multi-organ disorder. High blood pressure (hypertension) with or without proteinuria is usually considered an initial clinical sign of PE. The pathogenesis of pre-eclampsia is highly complex and likely involves multiple factors, including poorly developed uterine spiral arterioles, immunological issues, placental ischemia or infarction, and genetic abnormalities. Inflammatory cytokine production, regulated by cytokine gene polymorphisms, is one of the factors likely contributing to the development of PE. The present study aimed to assess IL-6, IL-1β, and Apo B-100 gene polymorphism and to evaluate the association of these polymorphisms with PE. Materials and Methods : This cross-sectional observational study involved 99 participants aged 16 to 45 years from Bahawal Victoria Hospital Bahawalpur, Punjab, Pakistan. The participants were divided into three groups: Group 1 (PE with severe hypertension), Group 2 (PE with hypertension), and Group 3 (control), each comprising 33 individuals. Maternal blood samples were collected, DNA was extracted, and molecular genetic analysis of the IL-6, IL-1β, and Apo B-100 genes was performed using the PCR-RFLP method. Allelic frequencies were compared, and statistical analysis was conducted using SPSS 25, applying the Hardy-Weinberg equation and chi-square test to evaluate the results. Results : There are differences in the distribution of allelic frequencies for IL-6 -174G/C (CC, GC, GG), IL-1β-511C/T (CC, CT, TT), and Apo B-100 2488 C/T (CC, CT, TT) between pre-eclamptic patients and the control group. The analysis using the Hardy-Weinberg equilibrium and chi-square test showed an association between the IL-6-174 G/C polymorphism and the severity of pre-eclampsia. Conclusions : The polymorphisms of the IL-6, IL-1β, and Apo B-100 genes revealed different alleles. The IL-6 gene alone was found to be in disequilibrium according to the Hardy-Weinberg equation, indicating a potential link to the severity of pre-eclampsia in the population studied.

Utilizing medicinal plants and other natural resources to prevent different types of human cancers is the prime focus of attention. Cervical cancer in women ranks as the fourth most common type of malignancy. The current study used gas chromatography-mass spectrometry (GC-MS) to identify the active phytochemical constituents from Caladium lindenii leaf extracts using ethanol (ECL) and n-hexane (HCL) solvents. Plant extracts were tested for potential cytotoxic effects on HeLa and HEK-293 T cells using the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) and the crystal violet assays. SYBR Green-based real-time PCR was performed to assess the mRNA expression profile of the apoptosis biomarkers (BCL-2 and TP53). The molecular interaction of the compounds with the targeted proteins (TP53, BCL2, EGFR, and HER2) was determined using molecular docking. GC-MS analysis revealed a total of 93 compounds in both extracts. The ECL extract significantly reduced the proliferation of HeLa cervical cancer cells, with an IC 50 value of 40 µg/mL, while HEK-293 T cells showed less effect (IC 50  = 226 µg/mL). The quantitative RT-PCR gene expression analysis demonstrated the ethanol extract regulated TP53 and BCL2 mRNA expressions in treated cancer cell samples. Heptanediamide, N,N'-di-benzoyloxy-(- 10.1) is the best-docked ligand with a TP53 target found in the molecular docking study, whereas EGFR/Clionasterol had the second highest binding affinity (- 9.7), followed by EGFR/Cycloeucalenol (- 9.6). It is concluded that ECL extract has promising anti-cervical cancer potential and might be valued for developing new plant-derived anticancer agents after further investigations., (© 2024. The Author(s).)

Methotrexate (MTX)-induced intestinal mucositis (IM) is a common side effect in cancer treatment that impairs the immune system and gut microbes, resulting in loss of mucosal integrity and gut barrier dysfunction. The quality of life and outcomes of treatment are compromised by IM. The present study was designed to investigate the mucoprotective potential of the benzimidazole derivative N-{4-[2-(4-methoxyphenyl)-1H-benzimidazole-1-sulfonyl] phenyl} acetamide (B8) on MTX-induced IM in mice. IM was induced by a single dose of MTX in mice and assessed by physical manifestations as well as biochemical, oxidative, histological, and inflammatory parameters. B8 (1, 3, 9 mg/kg) significantly reduced diarrhea score, mitigated weight loss, increased feed intake and, survival rate in a dose-dependent manner. Notably, B8 exhibited a mucoprotective effect evident through the mitigation of villus atrophy, crypt hypoplasia, diminished crypt mitotic figures, mucin depletion, and oxidative stress markers (GSH, SOD, MDA, and catalase concentration). Gene expression analysis revealed that B8 downregulated the mRNA expression of tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), IL-1β, and nuclear factor-κB (NF-κB) and concurrently upregulated IL-10 expression in contrast to the MTX group. Further, B8 significantly improved the luminal microflora profile by augmenting the growth of Lactobacillus spp. and reducing the number of pathogenic bacteria (E. coli). Additionally, the enzyme-linked immunoassay showed that B8 decreased the levels of pro-inflammatory cytokines. Our findings suggest that B8 had mucoprotective effects against MTX-induced IM and could be used as an adjunct in chemotherapy to deter this side effect., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: This study was conducted to evaluate the effects of vitamin C on apoptotic and proliferative genes in injured HepG2 cells., Methods: In silico analysis was performed using molecular docking of chemical compounds with vascular endothelial growth factor (VEGF). The different computational tools used were AutoDock Vina, BIOVIA DISCOVERY studio, and PyMOL. Drug likeness and toxicity were analyzed by SWISS ADMET. Cells that were 60-70% confluent were treated with different concentrations of hydrogen peroxide (H 2 O 2 ) (100-2000 μM) and ascorbic acid (30, 60, 90 μg/mL). The MTT cell proliferation assay was performed to compare the proliferative potential of HepG2 cells treated with H 2 O 2 or ascorbic acid with untreated HepG2 cells using 96-well plates., Results: The lowest binding energy of VEGF with vitamin C -5.2 kcal/mol and L-ascorbic acid-2 glycoside -4.7 kcal/mol was observed by in silico analysis. Vitamin C was selected because it exhibited a high interaction with VEGF and fulfilled Lipinski's rule, and had better oral viability and pharmacokinetics compared to L-ascorbic acid-2 glycoside. Cell viability assays showed that vitamin C had significant apoptotic effects (P < 0.0001). After treating HepG2 cells with ascorbic acid, reduced VEGF (angiogenesis) was observed as determined by apoptotic and proliferative gene expression. Ascorbic acid treatment of HepG2 cells led to downregulation of the proliferation markers, proliferating cell nuclear antigen, Ki67, and DNA topoisomerase II alpha. Increased apoptosis after treatment with vitamin C was observed due to upregulation of p53 and annexin V., Conclusion: The results of this study showed that vitamin C inhibited the growth of cancer cells, thus protecting HepG2 cells from oxidative stress. Vitamin C exhibited antiproliferative activity as observed in silico and in vitro , as well as by the inhibited expression of genes involved in protein synthesis., (© 2024 The Authors.)

Oral administration of BCS class IV anticancer agents has always remained challenging and frequently results in poor oral bioavailability. The goal of the current study was to develop hybrid nanoparticles (HNPs) employing cholesterol and poloxamer-407 to boost paclitaxel's (PTX) oral bioavailability. A series of HNPs with different cholesterol and poloxamer-407 ratios were developed utilizing a single-step nanoprecipitation technique. The PTX loaded HNPs were characterized systematically via particle size, zeta potential, polydispersity index, surface morphology, in vitro drug release, FTIR, DSC, XRD, acute oral toxicity analysis, hemolysis evaluation, accelerated stability studies, and in vivo pharmacokinetic analysis. The HNPs were found within the range of 106.6±55.60 - 244.5±88.24 nm diameter with the polydispersity index ranging from 0.20±0.03 - 0.51±0.11. SEM confirmed circular, nonporous, and smooth surfaces of HNPs. PTX loaded HNPs exhibited controlled release profile. The compatibility between the components of formulation, thermal stability, and amorphous nature of HNPs were confirmed by FTIR, DSC, and XRD, respectively. Acute oral toxicity analysis revealed that developed system have no deleterious effects on the animals' cellular structures. HNPs demonstrated notable cytotoxic effects and were hemocompatible at relatively higher concentrations. In vivo pharmacokinetic profile (AUC 0-∞ , AUMC 0-∞ , t 1/2, and MRT 0-∞ ) of the PTX loaded HNPs was improved as compared to pure PTX. It is concluded from our findings that the developed HNPs are hemocompatible, biocompatible and have significantly enhanced the oral bioavailability of PTX., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Apolipoprotein E (APOE) gene polymorphism has been implicated in the pathogenesis of various metabolic disorders, including type 2 diabetes mellitus (T2DM). Type 2 diabetes mellitus (T2DM) is a major public health concern worldwide, including in Pakistan. Cardiovascular problems linked with T2DM have a significant impact on individuals and society. The goal of this study is to investigate the relationship between Apolipoprotein E (ApoE) genotypes, dyslipidemia, and cardiovascular complications such as ischemic heart disease (IHD) and stroke. Methods: This study was carried out on 260 subjects divided into controls and diabetics. The diabetics were further divided into four subgroups such as D1: diabetics without cardiovascular issues, D2: diabetics with heart disease, D3: diabetics with stroke, and D4: diabetics with both heart disease and stroke. Anthropometric parameters (age, BMI) and risk factors (smoking, diabetes duration, hypertension) were assessed in all groups. Serum levels of TC, TG, LDL, HDL, VLDL, creatinine, BSF, and HbA1c were also measured. Apolipoprotein E gene polymorphism was determined using PCR-RFLP. Results: Hypertension, BMI, and dyslipidemia are defined as elevated levels of total cholesterol, triglycerides, LDL, and VLDL, and decreased levels of HDL. Uncontrolled hyperglycemia (elevated fasting blood sugar and glycated hemoglobin) in T2DM was linked to vascular complications such as IHD and stroke. Hypertension was prevalent in 79.3% of the population. Stage 2 hypertension was more prevalent in all age groups. It was also noted that common genotypes in the Pakistani population are 3/3, 4/4, 2/3, and 3/4. The frequency of genotypes 3/4 and 2/3 is highest in diabetics with stroke. Genotype 3/3 is present frequently in diabetics with IHD/stroke and patients with both these complications. However, genotype 4/4 is most frequently found in diabetics with IHD. Conclusions: It is concluded that BMI, hypertension, hyperglycemia, atherosclerosis, and dyslipidemia are linked with cardiovascular complications of type 2 diabetes. Apolipoprotein E gene polymorphism is associated with cardiovascular disease in patients with diabetes by affecting the lipid profile.

In recent years, a cancer research trend has shifted towards identifying novel therapeutic compounds from natural assets for the management of cancer. In this study, we aimed to assess the cytotoxic activity of Kigelia Africana (KA) extracts on breast cancer (MDA-MB-231 and MCF-7) and noncancerous kidney cells (HEK-293T) to develop an efficient anticancer medication. We used gas chromatography mass spectrometry (GC-MS to analyze the constituents of EKA and HKA extracts meanwhile the crystal violet and the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assays were used to examine the possible cytotoxic effects of plant extracts on our cancer cell lines along with non-cancerous control. The quantitative real-time PCR (RT-PCR) was run on cell samples to evaluate the differential expression of cell proliferative markers of cancer (BCL-2 and TP53). These phytochemicals have been reported to have binding affinity for some other growth factors and receptors as well which was evaluated by the in-silico molecular docking against Bcl2, EGFR, HER2, and TP53. Our Morphological observation showed a significant difference in the cell morphology and proliferation potential which was decreased under the effect of plant extracts treatment as compared to the control samples. The ethanol extract exhibited a marked antiproliferative activity towards MDA-MB-231 and MCF-7 cell lines with IC50 = 20 and 32 μg/mL, respectively. Quantitative RT-PCR gene expression investigation revealed that the IC50 concentration of ethanolic extract regulated the levels of mRNA expression of apoptotic genes. With the target and active binding site amino acids discovered in the molecular docking investigation, TP53/Propanoic acid, 3-(2, 3, 6-trimethyl-1, 4-dioxaspiro [4.4] non-7-yl)-, methyl ester (-7.1 kcal/mol) is the best-docked ligand. The use of this plant in folk remedies justifies its high in vitro anti-cancer capabilities. This work highlights the role of phytochemicals in the inhibition of cancer proliferation. Based on all these findings, it can be concluded that EKA extract has promising anti-proliferative effect on cancerous cells but more study is required in future to further narrow down the active ingredients of total crude extract with specific targets in cancer cells., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kalsoom et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aim: The liver plays a crucial role in biotransformation but it is susceptible to chemical-induced damage, known as hepatotoxicity. Traditional therapies for protecting the liver face significant challenges, including poor bioavailability, off-target effects, adverse reactions, drug breakdown, and inadequate uptake. These issues emphasize the need for precise, targeted therapeutic approaches against hepatotoxicity., Materials and Methods: The objective of our research was to develop a customized, biocompatible, and biodegradable nanodrug delivery system for hepatoprotection. We chose collagen hydrolyzed protein, or gelatin, as the base material and utilized solvent evaporation and nanoprecipitation methods to create nanoparticles with size ranging from 130 to 155 nm. The resulting nanoparticles exhibited a spherical and smooth surface, as confirmed by scanning and transmission electron microscopy., Key Findings: Bioactive aescin (AES), into these gelatin nanoparticles (AES-loaded gel NPs), we tested these nanoparticles using a hepatotoxicity model. The results were indicating a significant reduction in the levels of key biomolecules, including NF-κB, iNOS, BAX, and COX-2 and decreased serum levels of enzymes ALT and AST. This reduction correlated with a notable alleviation in the severity of hepatotoxicity. Furthermore, the treatment with AES-loaded gel NPs resulted in the downregulation of several inflammatory and liver-specific biomarkers, including nitrite, MPO, TNF-α, and IL-6., Significance: In summary, our study demonstrates that the AES-loaded gel NPs were markedly more effective in mitigating experimental hepatotoxicity when compared to the free aescin. The nanoparticles exhibited a propensity for suppressing liver damage, showcasing the potential of this targeted therapeutic approach for safeguarding the liver from harmful chemical insults., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Membrane fouling and high-strength membrane concentrate production are two limitations of membrane distillation (MD) for landfill leachate treatment. In this study, activated carbon- and biochar-based adsorption processes were integrated into a conventional MD system to overcome these limitations. The organic matter fractionations of the leachate were thoroughly investigated during the treatment. Membrane-reversible and irreversible foulants differed remarkably from the inlet leachate in the non-assisted MD system. Specifically, reversible foulants were characterized by a high abundance of humic-like fluorescent components, high-molecular-weight humic-size constituents, peptides, and unsaturated compounds. In contrast, irreversible foulants were enriched with fulvic-like fluorescent components, low-molecular-weight neutrals, unsaturated compounds, and polyphenols. The adsorption-based pre-treatment effectively removed foulant precursors from landfill leachate, with a relatively higher (20%) adsorption performance for specific biochar used in this study than for activated carbon. Compared with the non-assisted MD system, the biochar-assisted MD system showed improved performance, achieving 40% overall membrane flux recovery, 42% higher filtration fluxes, and 53% lower concentrate production. In addition, a 15% higher removal of irreversible foulants was observed as compared to the reversible foulants, which can potentially increase the membrane lifespan. This study demonstrates the effectiveness of an adsorption-assisted MD system supported by increased filtration, membrane fouling alleviation, and low-strength leachate concentrate generation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

A new matrix framework is presented in this study for the improved ionization efficiency of complex mixtures by matrix-assisted laser desorption ionization (MALDI) mass spectrometry/imaging. Five nitro indole (NI) derivatives [3-methyl-4-nitro-1H-indole (3,4-MNI), 3-methyl-6-nitro-1H-indole (3,6-MNI), 2,3-dimethyl-4-nitro-1H-indole (2,3,4-DMNI), 2,3-dimethyl-6-nitro-1H-indole (2,3,6-DMNI), and 4-nitro-1H-indole (4-NI)] were synthesized and shown to produce both positive and negative ions with a broad class of analytes as MALDI matrices. NI matrices were compared to several common matrices, such as 2,5-dihydroxybenzoic acid (DHB), alpha-cyano-4-hydroxylcinnamic acid (CHCA), sinapinic acid (SA), 1,5-diaminonaphthelene (1,5-DAN), and 9-aminoacridine (9-AA), for the analysis of lipid, peptide, protein, glycan, and perfluorooctanesulfonic acid (PFOS) compounds. 3,4-MNI demonstrated the best performance among the NI matrices. This matrix resulted in reduced ion suppression and better detection sensitivity for complex mixtures, for example, egg lipids/milk proteins/PFOS in tap water, while 2,3,6-DMNI was the best matrix for blueberry tissue imaging. Several important aspects of this work are reported: (1) dual-polarity ion production with NI matrices and complex mixtures; (2) quantitative analysis of PFOS with a LOQ of 0.5 ppb in tap water and 0.05 ppb in MQ water (without solid phase extraction enrichment), with accuracy and precision within 5%; (3) MALDI imaging with 2,3,6-DMNI as a matrix for plant metabolite/lipid identification with ionization enhancement in the negative ion mode m / z 600-900 region; and (4) development of a thin film deposition under/above tissue method for MALDI imaging with a vacuum sublimation matrix on a high-vacuum MALDI instrument.

COVID-19, stemming from SARS-CoV-2, poses a formidable threat to global healthcare, with a staggering 77 million confirmed cases and 690,067 deaths recorded till December 24, 2023. Given the absence of specific drugs for this viral infection, the exploration of novel antiviral compounds becomes imperative. High-throughput technologies are actively engaged in drug discovery, and there is a parallel effort to repurpose plant-based molecules with established antiviral properties. In this context, the review meticulously delves into the potential of plant-based folk remedies and existing molecules. These substances have showcased substantial viral inhibition in diverse in vivo, in silico , and in vitro studies, particularly against critical viral protein targets, including SARS-CoV-2. The findings position these plant-based molecules as promising antiviral drug candidates for the swift advancement of treatments for COVID-19. It is noteworthy that the inherent attributes of these plant-based molecules, such as their natural origin, potency, safety, and cost-effectiveness, contribute to their appeal as lead candidates. The review advocates for further exploration through comprehensive in vivo studies conducted on animal models, emphasizing the potential of plant-based compounds to help in the ongoing quest to develop effective antivirals against COVID-19., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

In this study, we reported the synthesis of 1-(4-bromobenzoyl)-1,3-dicyclohexylurea by the reaction of DCC ( N , N '-dicyclohexylcarbodiimide) with 4-bromobenzoic acid. Subsequently, we further synthesized a new series of 1-(4-arylbenzoyl)-1,3-dicyclohexylurea ( 5a - g ) derivatives using a Suzuki cross-coupling reaction between 1-(4-bromobenzoyl)-1,3-dicyclohexylurea ( 3 ) and various aryl/heteroaryl boronic acids ( 4 ). Thus, density functional theory (DFT) calculations have been performed to examine the electronic structure of the synthesized compounds ( 3 , 5a - g ) and to calculate their spectroscopic data. Moreover, optimized geometries and thermodynamic properties, such as frontier molecular orbitals (HOMO, LUMO), molecular electrostatic potential surfaces, and reactivity descriptors, were also calculated at the PBE0-D3BJ/def2-TZVP/SMD 1,4-dioxane level of theory to validate the structures of the synthesized compounds., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Hepatocellular carcinoma is the fifth most prevalent cancer worldwide. The emergence of drug resistance and other adverse effects in available anticancer options are challenging to explore natural sources. The current study was designed to decipher the Arnebia nobilis (A. nobilis) extracts for detecting phytochemicals, in-vitro evaluation of antioxidative and cytotoxic potentials, and in-silico prediction of potent anticancer compounds. The phytochemical analysis revealed the presence of flavonoids, phenols, tannins, alkaloids, quinones, and cardiac glycosides, in the ethanol (ANE) and n-hexane (ANH) extracts of A. nobilis. ANH extract exhibited a better antioxidant potential to scavenge DPPH, nitric oxide and superoxide anion radicals than ANE extract, which showed better potential only against H 2 O 2 radicals. In 24 h treatment, ANH extract revealed higher cytotoxicity (IC 50 value: 22.77 µg/mL) than ANH extract (IC 50 value: 46.74 µg/mL) on cancer (HepG2) cells without intoxicating the normal (BHK) cells using MTT assay. A better apoptotic potential was observed in ANH extract (49.10%) compared to ANE extract (41.35%) on HepG2 cells using the annexin V/PI method. GCMS analysis of ANH extract identified 35 phytocompounds, from which only 14 bioactive compounds were selected for molecular docking based on druggability criteria and toxicity filters. Among the five top scorers, deoxyshikonin exhibited the best binding affinities of - 7.2, - 9.2, - 7.2 and - 9.2 kcal/mol against TNF-α, TGF-βR1, Bcl-2 and iNOS, respectively, followed by ethyl cholate and 2-Methyl-6-(4-methylphenyl)hept-2-en-4-one along with their desirable ADMET properties. The phytochemicals of ANH extract could be used as a promising drug candidate for liver cancer after further validations., (© 2023. The Author(s).)

Dissolved organic matter (DOM) in the sediment matrix affects contaminant remediation through consumption of oxidants and binding with contaminants. Yet the change in DOM during remediation processes, particularly during electrokinetic remediation (EKR), remains under-investigated. In this work, we elucidated the fate of sediment DOM in EKR using multiple spectroscopic tools under abiotic and biotic conditions. We found that EKR led to significant electromigration of the alkaline-extractable DOM (AEOM) toward the anode, followed by transformation of the aromatics and mineralization of the polysaccharides. The AEOM remaining in the cathode (largely polysaccharides) was resistant to reductive transformation. Limited difference was noted between abiotic and biotic conditions, indicating the dominance of electrochemical processes when relatively high voltages were applied (1-2 V/cm). The water-extractable organic matter (WEOM), in contrast, showed an increase at both electrodes, which was likely attributable to pH-driven dissociations of humic substances and amino acid-type constituents at the cathode and the anode, respectively. Nitrogen migrated with the AEOM toward the anode, but phosphorus remained immobilized. Understanding the redistribution and transformation of DOM could inform studies on contaminant degradation, carbon and nutrient availability, and sediment structural changes in EKR., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Reticular Oral lichen planus (OLP) is a chronic autoimmune disease that presents as fine, white, linear and lace like lesions of the oral cavity referred to as Wickham striae. The clinical characteristics of 30 patients with reticular oral lichen planus is presented so that cases are not missed/misdiagnosed by ENT surgeons. The clinical records noted for each patient were gender, age and clinical presentation of reticular OLP (site affected, presence of symptoms and extraoral manifestations of the disease, smoking habit, and consumption of alcoholic beverages). Twenty patients were females (66.7%) and 10 (33.3%) were males giving a female to male ratio of 2:1. Majority of patients (50%) among both males and females were in the age group of 31-40 years followed by 41-50 years (20%). Oral discomfort/burning sensation was the chief symptom in 24 (80%) patients followed by asymptomatic oral white patches in 5 (16.6%).The buccal (cheek) mucosa was the site most affected (76.8%) followed by the buccal mucosa plus retromolar trigone mucosa (10%) and tongue (6.6%), Extraoral lesions were observed in 2 (6.6%) of patients at presentation with oral lesions and were on the nails in 1 patient and wrist in 1 patient. Tobacco smoking, alcohol use, diabetes and hypertension were reported in 3 (10%), 0%, 2 (6.7%) and 4 (13.3%) patients respectively. ENT surgeons routinely see patients with oral discomfort/oral ulcerations and as such they should be well versed with classical clinical characteristics of reticular oral lichen planus., Competing Interests: Conflict of interestThere is no potential conflict of interest., (© Association of Otolaryngologists of India 2022. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

A composite manganese-based catalytic ceramic membrane (Mn-CCM) was developed by a solid-state sintering method, and its effectiveness toward activation of peroxymonosulfate (PMS) for the degradation of 11 pharmaceutical and personal care products (PPCPs) mixture was tested. The optimized Mn-CCMs/PMS system showed remarkable degradation efficiencies for PPCPs mixture with total removal >90% in ultrapure water, river water and natural organic matter (NOM) solution. The Mn-CCMs/PMS system showed the contribution of different phenomena in PPCPs removal in the order of catalytic oxidation (54.7%, Mn-CCMs/PMS) > noncatalytic oxidation (42.3%, PMS oxidation) > adsorption (3.0%, by Mn-CCMs). The singlet oxygen ( 1 O 2 ) was the dominant reactive oxygen specie for the degradation of PPCPs in all water matrices proved by the quenching experiments and electro-paramagnetic resonance (EPR) spectroscopy. The extraordinary stability of Mn-CCMs for the activation of PMS has been noted in terms of repeatability experiments for PPCPs degradation with fewer leaching of Mn (1.9 to 3.6 µg/L). Mineralization was achieved in the range of 28-65% for different water matrices. The toxicity of the PPCPs mixture was reduced by 85.9%. The Mn-CCMs/PMS system showed a reduction (25-100%) in precursors of different carbon- and nitrogen-based disinfection by-products. This study found the Mn-CCMs/PMS system as a feasible purification unit for removing trace concentrations of PPCPs (ng/L) in real drinking water matrices., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Applications of electrochemical advanced oxidation processes are rising in drinking water treatment for effective mitigation of refractory organic compounds. This study explored the fate of natural organic matter (NOM) (lake water and standard NOM (SRNOM solution)) at molecular-level in the reactive electrochemical membrane (REM) system utilizing Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). Fluorescence spectroscopy showed above 90 % removal of the humic-like component in both lake water and SRNOM solution in 10 min of REM operation compared to 70-80 % removal of the fulvic-like component after 30 min. REM-based treatment effectively eliminated (>70 %) the disinfection byproduct precursors. The lake water, sharing ~70 % of similar compounds with SRNOM, displayed a different propensity toward electrochemical oxidation, and its finished water was characterized with relatively lower double-bond equivalent (DBE), nominal oxidation state of carbon (NOSC), and aromaticity compared to that of SRNOM. The chloride ions in the water matrix of lake water impacted the electrochemical oxidation and generated significantly different transformation products than SRNOM solution. The heteroatoms (N and S) containing compounds (CHON and CHOS) were preferentially degraded in lake water; however, CHOS compounds were removed fewer in SRNOM. The electrosorption and electrochemical oxidation on the REM surface were the significant contributors for NOM removal. The newly formed compounds were mostly retained on the REM surface and fewer were released in finished water. This study is believed to help understand the fate of NOM in real source drinking water during electrochemical treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background and Objectives: The main objective of the present study was to determine the role of oxidative markers (glutathione (GSH), advanced oxidation protein products (AOPP), advanced glycation end products (AGEs), and malondialdehyde (MDA)) and inflammatory biomarkers (interleukin-6 IL-6, tumor necrosis factor α (TNF-α), myeloperoxide (MPO)) in the development of diabetic nephropathy along with routinely used biochemical parameters. Materials and Method: This was a case control study. All the selected patients were screened and enrolled by convenient non-probability sampling technique at the Jinnah hospital in Lahore. Informed consent was obtained before enrollment of the study subjects. A total of 450 patients enrolled in the study, and they were divided into three groups, 150 subjects with type 2 diabetes and 150 diagnosed diabetic nephropathy (DN) vs. 150 healthy individuals as a control group. Five mL of venous blood sample was taken from the antecubital vein of each participant. Statistical analysis was performed by SPSS. The results of all variables were evaluated by using one way ANOVA. Results: The mean value of biochemical parameters (WBCs, platelets, prothrombin time, HbA1c, glucose, urinary albumin-to creatinine ratio (UACR), triglycerides, LDL, HDL, serum creatinine, urinary albumin (creatinine)) were increased and Hb (g/dL), red blood cells (RBCs), hematocrit (Hct), free serum insulin levels, and estimated glomerular filtration rate (eGFR) were decreased in the nephropathy group compared to the control and type 2 diabetes groups. The mean values of MDA, AGE, and AOPPs in type 2 diabetes and diabetic nephropathy were significantly increased compared to the control group. GSH level was decreased in type 2 diabetics and DN patients as compared to the control group. In addition, IL-6, TNFα, and MPO levels were also increased in case of diabetes nephropathy compared to controls. Conclusions: ROS mediated injuries can be prevented by the restoration of an antioxidant defense system, through the administration of antioxidant agents. Moreover, increased levels of inflammatory mediators are responsible for enhancing inflammation in patients with diabetic nephropathy.

A ceramic membrane reactor (CMR) integrated with in-situ UV/O 3 was assessed for post-treatment of the effluent out of an up-flow anaerobic sludge blanket (UASB) reactor treating real textile wastewater, focusing on the transformation of dissolved organic matter (DOM). Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) revealed the transformation of heteroatomic DOM containing S, N or both to simpler DOM containing mainly C, H, and O atoms. The decreased N contents in products (N/C = 0.0249) compared to precursors (N/C = 0.0311) and the higher O/C ratios in the N-containing products suggest the removal of R-NH 2 groups accompanying DOM oxidation. While, S-containing compounds in the products had lower O/C and H/C ratios, suggesting a reduced state and the transformation of R-SO 3 to R-S-R. H-abstraction and OH addition were identified as the primary oxidation mechanisms, thus enhancing the dominance of highly unsaturated and phenolic DOM in the effluent (70.3%) compared to the feed (56.6%). The double bond equivalent (DBE) was also increased by 26% in the effluent compared to the feed and by 33% in products compared to precursors. These findings help understand the DOM transformation in UV/O 3 -assisted ceramic membrane reactors and call for comprehensive toxicity analyses of effluents from the advanced oxidation processes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Data regarding the therapeutic potential of Caladium lindenii ( C. lindenii ) are insufficient. It becomes more important to explore plants as an alternative or palliative therapeutics in deadly diseases around the globe. The current study was planned to explore C. lindenii for its anticancer activity of ethanolic and hexane extracts of C. lindenii leaves against hepatic carcinoma (HepG2) and human embryonic kidney (HEK293T) cell lines. HepG2 and HEK293T cells were treated with 10, 50, 100, 200, and 400  μ g/mL of ethanolic and hexane extracts of C. lindenii and were incubated for 72 h. Antiproliferative activity was measured by 3-(4,5-dimethylthiazol-2yl)-2,5-biphenyl tetrazolium bromide (MTT) assay, and percentage viability were calculated through crystal violet staining and cellular morphology by Floid Cell Imaging Station. The study showed ethanolic extract exhibiting a significantly higher antiproliferative effect on HepG2 (IC50 = 31 μ g/mL) in a concentration-dependent manner, while HEK293T (IC50 = 241 μ g/mL) cells showed no toxicity. Hexane extract exhibited lower cytotoxicity (IC50 = 150 μ g/mL) on HepG2 cells with no effect on HEK293T (IC50 = 550 μ g/mL). On the other hand, the percentage viability of HepG2 cells was recorded as 78%, 67%, 50%, 37%, and 28% by ethanolic extracts, and 88%, 80%, 69%, 59%, and 50% by hexane extracts at tested concentrations of both extracts. Toxicity assay showed significantly safer ranges of percentage viabilities in normal cells (HEK293T), i.e., 95%, 90%, 88%, 76%, and 61% with ethanolic extract and 97%, 95%, 88%, 75%, and 62% with hexane extract. The assay validity revealed 100% viability in the control negative (dimethyl sulfoxide treated) and less than 45% in the control positive (cisplatin) on both HepG2 and HEK293T cells. Morphological studies showed alterations in HepG2 cells upon exposure to >50  μ g/mL of ethanolic extracts and ≥400  μ g/mL of hexane extracts. HEK293T on the other hand did not change its morphology against any of the extracts compared to the aggressive changes on the HepG2 cell line by both extracts and positive control (cisplatin). In conclusion, extracts of C. lindenii are proved to have significant potential for cytotoxicity-induced apoptosis in human cancer HepG2 cells and are less toxic to normal HEK293T cells. Hence C. lindenii extracts are proposed to be used against hepatocellular carcinoma (HCC) after further validations., Competing Interests: The authors declare no competing interests., (Copyright © 2022 Aasia Kalsoom et al.)

The excess sludge generated from the activated sludge process remains a big issue. Sustainable approaches that achieve in situ sludge reduction with satisfactory effluent quality deserve attention. This study explored the sludge reduction performance of sulfidogenic anoxic-oxic-anoxic (AOA) membrane bioreactors. The dynamics of the microbial community and metabolic pathways were further analyzed to elucidate the internal mechanism of sludge reduction. Compared with the conventional anoxic-oxic-oxic membrane bioreactor (MBR control ), AOA S150 (150 mg/L SO 4 2- in the membrane tank) and AOA S300 (300 mg/L SO 4 2- in the membrane tank) reduced biomass production by 40.39% and 47.45%, respectively. The sulfide reduced from sulfate could enhance the sludge decay rate and decrease sludge production. Extracellular polymeric substances (EPSs) destruction and aerobic lysis contributed to sludge reduction in AOA bioreactors. The relative abundance of Bacteroidetes (phylum), sulfate-reducing bacteria (SRB, genus), and Ignavibacterium (genus) increased in AOA bioreactors compared with MBR control . Our metagenomic analysis indicated that the total enzyme-encoding genes involved in glycolysis, denitrification, and sulfate-reduction processes decreased over time in AOA S300 and were lower in AOA S300 than AOA S150 at the final stage of operation. The excess accumulation of sulfide in AOA S300 may inactive the functional bacteria, and sulfide inhibition induced sludge reduction.

Alzheimer's disease (AD) is a neurodegenerative disorder that causes progressive loss of cognitive functions like thinking, memory, reasoning, behavioral abilities, and social skills thus affecting the ability of a person to perform normal daily functions independently. There is no definitive cure for this disease, and treatment options available for the management of the disease are not very effective as well. Based on histopathology, AD is characterized by the accumulation of insoluble deposits of amyloid beta (Aβ) plaques and neurofibrillary tangles (NFTs). Although several molecular events contribute to the formation of these insoluble deposits, the aberrant post-translational modifications (PTMs) of AD-related proteins (like APP, Aβ, tau, and BACE1) are also known to be involved in the onset and progression of this disease. However, early diagnosis of the disease as well as the development of effective therapeutic approaches is impeded by lack of proper clinical biomarkers. In this review, we summarized the current status and clinical relevance of biomarkers from cerebrospinal fluid (CSF), blood and extracellular vesicles involved in onset and progression of AD. Moreover, we highlight the effects of several PTMs on the AD-related proteins, and provide an insight how these modifications impact the structure and function of proteins leading to AD pathology. Finally, for disease-modifying therapeutics, novel approaches, and targets are discussed for the successful treatment and management of AD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mumtaz, Ayaz, Khan, Manzoor, Ganayee, Bhat, Dar, Alghamdi, Hashem, Dar, Ashraf and Maqbool.)

Conventional and advanced biological wastewater treatment systems generate excess sludge, which causes socio-economic and environmental issues. This study investigated the performance of membrane-controlled anoxic-oxic-anoxic (AOA) bioreactors for in-situ sludge reduction compared to the conventional anoxic-oxic-oxic membrane bioreactor (MBR control ). The membrane units in the AOA bioreactors were operated as anoxic reactors at lower sludge recirculation rates to achieve hydrolysis of extracellular polymeric substances (EPS) and extensive endogenous respiration. Compared to MBR control , the AOA bioreactors operated with 90%, and 80% recirculation rates reduced the sludge growth up to 19% and 30%, respectively. Protein-like components were enriched in AOA bioreactors while fulvic-like components were dominant in MBR control . The growth of Dechloromonas and Zoogloea genra was promoted in AOA bioreactors and thus sludge reduction was facilitated. Metagenomics analysis uncovered that AOA bioreactors exhibited higher proportions of key genes encoding enzymes involved in the glycolysis and denitrification processes, which contributed to the utilization of carbon sources and nitrogen consumption and thus sludge reduction.

Acacia modesta (AM) and Opuntia monocantha (OM) are distributed in Pakistan, Afghanistan and India. Both of these plants have different pharmacological properties. This study was designed to evaluate anticancer potential of Acacia modesta (AM) and Opuntia monocantha (OM). Liver cancer cell line HepG2 was used for assessment of anticancer activity. For the evaluation of anti-proliferative effects, cell viability and cell death in all groups of cells were evaluated via MTT, crystal violet and trypan blue assays. For the evaluation of apoptosis ELISA of p53 performed. Furthermore, LDH assay to find out the ability of malignant cells to metabolize pyruvate to lactate and antioxidant enzymes activity (GSH, CAT and SOD) at the end HPLC was performed to find active compound of AM and OM. Cytotoxicity (MTT), Viability assays (trypan blue, crystal viability, MUSE analysis) showed more dead, less live cells in plant treated groups with increase of concentration. Scratch assay for the anti-migratory effect of these plants showed treated groups have not ability to heal scratch/wound. ELISA of p53 for cellular apoptosis showed more release of p53 in treated groups. Antioxidant assay via glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) showed less anti-oxidative potential in treated cancer groups. LDH assay showed more lactate dehydrogenase release in treated groups compared with untreated. HPLC analysis showed the presence of phytochemicals such as steroids, alkaloids, phenols, flavonoids, saponins, tannins, anthraquinone and amino acids in AM and OM plant extracts. Based on all these findings, it can be concluded that ethanolic extracts of Acacia modesta and Opuntia monocantha have promising anti-cancer potential.

Herein, a biosorbent was prepared from cucumber peels modified with ZnO nanoparticles (CPZiONp-composite) for the biosorption of metribuzin. Characterization of the composite was accomplished using FTIR, SEM, EDX, surface area pore size analyzer and pH of point of zero charge (pH pzc ). Biosorption study was executed in batch concerning the impact of pH, composite dose, contact time, initial metribuzin concentration and temperature. The biosorption depends on pH and maximum biosorption was acquired at pH 3.0. Surface chemistry of the composite was studied by determining the pH pzc and was found to be 6.1. The biosorption nature was investigated using isotherms and was assessed that Freundlich isotherm is well suited for the fitting of the biosorption data owing to the highest R 2 . The maximum biosorption capacity of CPZiONp-composite was found to be 200 mg g -1 . The biosorption data were fitted in to different kinetic models and the outcomes suggesting that pseudo second order is a satisfactory model to interpret the biosorption data owing to the highest R 2 . Thermodynamic parameters for instance entropy, enthalpy and Gibbs free energy were computed and revealed that biosorption of metribuzin onto CPZiONp-composite is spontaneous and exothermic process., (© 2022. The Author(s).)

This research evaluated the performance of reactive electrochemical ceramic membrane (REM) in treating secondary effluent and investigated the fate of dissolved organic matter (DOM) at the molecular level. The role of adsorption, electrosorption, and oxidation in DOM removal was comprehensively elucidated based on fluorescence spectroscopy and high-resolution mass spectrometry (FT-ICR MS). Among the fluorescence components (C1-C3) in secondary effluent, microbial humic-like C2 showed fewer adsorption on the REM surface without applying an electrical potential. The electrosorption helped an enhanced uptake of all DOM components and transformed them onto the electrode surface. The fluorescence components and all three fractions (hydrophilic, transphilic, and hydrophobic) were rapidly degraded, and finished water with stable DOM was obtained. The leading degradation phenomena were the change of the unsaturated compounds to the aliphatic and transformation of large-sized molecules to medium and small-sized ones. Above 70% of the compounds in the secondary effluent acted as precursors, which were mineralized/degraded and transformed products were found on the REM surface and in the finished water. The compounds containing sulfur (CHOS) were easily and preferably degraded/mineralized, followed by the compounds containing nitrogen (CHON) and CHO. The oxidation of DOM led to the extensive formation of organo-chlorinated compounds, which contributed above 80% in products. Overall, the combination of fluorescence spectroscopy and FT-ICR MS provided unique behavior of DOM in the secondary effluent toward electro-oxidation in the REM system. These findings could help explore the potential of REM for different water matrices to project the possible composition of DOM in the finished water., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Using a grounded theory approach, this qualitative study aimed to highlight the evolving technological dimensions of death and mourning practices and its transfer from a set physical setting to virtual and open space. The study was carried on 30 participants from Kashmir. Data was collected using in-depth face-to-face interviews and field notes were also used to capture non-verbal communication. The results of the study revealed that a considerable shift is being witnessed so far as death and mourning practices in Kashmir are concerned. The physical space is shrinking and giving way for virtual spaces to play their role in practices related to death and mourning.

Genetic immunization is a simple, cost-effective, and powerful tool for inducing innate and adaptive immune responses to combat infectious diseases and difficult-to-treat illnesses. DNA immunization is increasingly used in the generation of monoclonal antibodies against targets for which pure proteins are unavailable or are difficult to express and purify (e.g., ion channels and receptors, transmembrane proteins, and emerging infectious pathogens). Genetic immunization has been successfully utilized in small inbred laboratory animals (mostly rodents); however, low immunogenicity of DNA/RNA injected into large mammals, including humans, is still a major challenge. Here, we provide a method for the genetic immunization of llamas, using a combination of biolistic transfection with a gene gun and intradermal injection with a DERMOJET® device, to elicit heavy-chain IgG responses against epidermal growth factor receptor (EGFR). We show the technique can be used to generate single-domain antibodies (VHHs) with nanomolar affinities to EGFR. We provide methods for gene gun bullet preparation, llama immunization, serology, phage-display library construction and panning, and VHH characterization., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Currently, artificial oocyte activation has attracted wide attention in assisted reproduction due to extensive range of applications, particularly in somatic cell nuclear transfer and deriving pluripotent stem cell lines and it is the unique model to determine the role of paternal genome. Numbers of artificial activating agents have been used extensively to induce the oocytes activation; however, embryos developmental competency of artificially activated oocytes is still very low. In the present study, we determined the functional impact of strontium chloride supplementation with gold nanoparticles (AuNPs) in artificial oocytes activation and subsequent embryonic development. Oocytes were activated artificially in the culture medium containing 250 nM AuNPs with constant concentration of strontium chloride 10.00 mM. We found that adding 250 nM AuNPs with constant concentration of strontium chloride (10.00 mM for 3 hr) in culture medium improves the proportion of embryos reaching to the morula and blastocyst stages from 61.00% and 42.00% (controls) to 75.00% and 58.00% (250 nM AuNPs), respectively. In addition, foster mothers receiving AuNPs-treated embryos showed more implantation percentage and pregnancy rate relative to females received control embryos. Finally, embryos treated with 250 nM AuNPs concentration showed no toxic effect in term of blastocyst development. Collectively, our findings suggest the potential role of AuNPs in early embryonic development for mouse oocytes activated artificially and provide new insights in the field of animal biotechnology and assisted reproduction in humans., Competing Interests: There is no conflict of interest to declare., (© 2021 Urmia University. All rights reserved.)

The increasing release of nutrients to aquatic environments has led to great concern regarding eutrophication and the risk of unwanted algal blooms. Based on observational data of 20 water quality parameters measured on a monthly basis at 40 stations from 2011 to 2020, this study applied different Machine Learning (ML) algorithms to suggest the best option for algal bloom prediction in the Han River, a large river in South Korea. Eight different ML algorithms were categorized into several groups of statistical learning, regression family, and deep learning, and were then compared for their suitability to predict the chlorophyll-derived trophic index (TSI-Chla). ML algorithms helped identify the most important water quality parameters contributing to algal bloom prediction. The ML results confirmed that eutrophication and algal proliferation were governed by the complex interplay between nutrients (nitrogen and phosphorus), organic contaminants, and environmental factors. Of the models tested, the adaptive neuro-fuzzy inference system (ANFIS) exhibited the best performance owing to its consistent and outperforming prediction both quantitatively (i.e., via regression) and qualitatively (i.e., via classification), which was evidenced by the lowest value of mean absolute error (MAE) of 0.09, and the highest F1-score, Recall and Precision of 0.97, 0.98 and 0.96, respectively. In a further step, a representative web application was constructed to assist common users to predict the trophic status of the Han River. This study demonstrated that ML techniques are not only promising for highly accurate water quality modeling of urban rivers, but also reduce time and labor intensity for experiments, which decreases the number of monitored water quality parameters, providing further insights into the driving factors of water quality deterioration. They ultimately help devise proactive strategies for sustainable water management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The supplementation of Selenium-enriched probiotics is effective in reducing oxidative stress and maintaining meat quality stability in broiler chicken especially under heat stress. An experimental study was conducted to perform Comparative analysis of Selenium yeast with inorganic Se in broilers under heat stress. A total of 120 broilers chicks of one day were assigned to 4 groups each consisting 30 chicks fed on same basal diet but different selenium sources. The basal diet of group D1 was not supplemented with Se source (Negative control), group D2 basal diet was supplemented with inorganic selenium (Sodium selenite 0.22mg/Kg starter phase and 0.15mg/Kg finisher phase), group D3 basal diet was supplemented with commercially available organic selenium (Seleno-methionine 0.22mg/Kg starter phase and 0.15mg/Kg finisher phase) and group D4 basal diet was supplemented with self-developed organic selenium (Se-enriched yeast 0.22mg/Kg starter phase and 0.15mg/Kg finisher phase). The performance parameters i.e. feed intake (FI), live body weight (BW) and FCR were not significantly (p>0.05) effected by selenium supplementation in the starter phase but were significantly (p<0.05) effected in the finisher phase. Selenium supplementation significantly (p<0.05) effected serum Se level in different supplemented groups. Higher serum Se value (58.20±0.06) was recorded in D4 group. Similarly significantly lower selenium value was recorded for D4 and higher was recorded for D1 (11.36±0.08). However lower serum Paraoxonase (PON) value was recorded for D4 (13.24±0.01) and higher for D1 (13.33±0.03). Comparatively self-developed Se enriched yeast increased the Se accumulation and improved antioxidant system. Glutathione peroxidase (GPx) was found higher in D4 (12.333±0.03) followed by D3, D2 and D1 respectively. Whereas superoxide dismutase (SOD) was significantly lower (p<0.05) in D4 (0.1437±0.003) followed by D3 (0.1457±0.002). Selenium supplementation increased the bird's survival rate. Birds fed on Se enriched yeast showed higher Se deposition and better antioxidant capacity as compared to other sources of selenium. Se-enriched yeast displayed an improved result on Se deposition in tissues, and oxidative capacity, meat tenderness and immune response level as compared to other sources of selenium.

In this study, we used stable isotope-labeled soluble microbial products (SMP) and substrates to explore their assimilation into the formation of new biological products (i.e., extracellular polymeric substances and biomass) in two adjacent sequencing batch reactors. The isotope labeling approach along with fluorescence spectroscopy allowed us to distinguish between refractory and labile portions of SMP constituents as well as their roles in the formation of extracellular polymeric substances (EPS). Comparison of SMP fluorescence and the specific UV absorbance values between the two reactors revealed the presence of humic-like aromatic substances in the non-consumable part of SMP, which can be ultimately released as effluent organic matter. Parallel factor analysis modeling of fluorescence spectra showed that the hydrolysis of EPS contents mostly resulted in humic-like components in SMP rather than protein-like components, which were initially abundant in EPS (>80%). From variations in carbon and nitrogen isotopic contents in EPS and biomass, it was found that carbon-containing substrates were enriched faster than their nitrogenous counterparts. The contributions to new EPS formation reached 87.5% for carbon and 60.5% for nitrogen. Meanwhile, the isotopic tracking of the labeled SMP revealed that only 11.0% and 11.9% of carbon and 13.3% and 11.6% of nitrogen from the influent SMP were finally assimilated into EPS and biomass, respectively. In contrast, the isotopic enrichment in SMP was higher (~50%) than that of EPS and biomass, indicating the low bioavailability and refractory nature of the feed SMP. This study proposed a promising approach for estimating the relative contributions of different forms of labile substrate and SMP to the formation of EPS in activated sludge processes. This approach could be suggested as a versatile method for establishing the kinetics, substrate element flow, mass balance on organic substrates and nutrients, as well as for tracking the consumption and uptake pathways of hazardous materials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The occurrence of mutagenic and carcinogenic N-nitrosamines in drinking water is of great concern. In this study, dynamics and removal of nine N-nitrosamines in three drinking water treatment systems of a southern city of China are monitored during one year of sampling. The impacts of physicochemical treatment units on the removal and generation of N-nitrosamines were evaluated. The O 3 and KMnO 4 based pre-oxidation units have caused an increase in N-nitrosamines concentration, with O 3 showing the substantial generation of N-nitrosamines. The carbon filter and ultrafiltration membrane units were found effective in removing N-nitrosamine precursors. These drinking water treatment systems have been useful in removing N-nitrosamine precursors; meanwhile, a slight decrease was found in already formed N-nitrosamines concentration. However, N-nitrosomorpholine (NMOR) and N-nitrosodiphenylamine (NDPhA) were found resistant toward all kinds of physicochemical treatments, and negligible changes in concentration were noted in all drinking water treatment systems. The distribution networks in the city provided an effective contact period to residual chlorine and precursors, which caused an increase in N-nitrosamines concentration. Overall, N-nitrosodimethylamine (NDMA) and N-nitroso-diethylamine (NDEA) have been found near the cancer risk threshold (10 -6 ) in all of the drinking water treatment systems, while the remaining seven N-nitrosamines were found below the risk level., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Psoriasis and atopic dermatitis are common among older adults (≥65 years old), but clinical trials often exclude that population., Objective: To synthesize evidence from observational studies on the safety of systemic therapies (conventional or biologic) for psoriasis and atopic dermatitis among older adults in a systematic review., Methods: We searched MEDLINE and EMBASE (inception to October 31, 2019) and included observational studies reporting adverse events among older people treated with systemic therapy for psoriasis or atopic dermatitis. Outcomes were death, hospitalization, emergency department visits, infections, major cardiovascular events, renal toxicity, hepatotoxicity, and cytopenias. We assessed study quality using the Newcastle-Ottawa Scale., Results: We included 22 studies on treatment for psoriasis and 2 for atopic dermatitis. Most studies were small and non-comparative and 20 of 24 were low quality. Studies comparing safety between medications or medication classes or between older and younger adults did not show apparent differences but had wide confidence intervals around relative effect estimates. Heterogeneity of study design and reporting precluded quantitative synthesis., Conclusions: There is scant evidence on the safety of conventional systemic and biologic medications for older adults with psoriasis or atopic dermatitis; older adults and their clinicians should be aware of this evidence gap.

The presence of carcinogenic N-nitrosamines and dissolved organic matter (DOM) in freshwater is a significant concern from the perspective of public health and drinking water treatment plant operation. This study investigated the N-nitrosamines concentration and their precursors' distributions, and DOM composition in four reservoirs located in a southern city of China. A total of 22 renowned precursors were identified. Precursors from industrial and pharmaceutical origins were found to be dominant in all reservoirs; however, traces of pesticide-based precursors, i.e. pirimicarb and cycluron were also found. The distribution of nine N-nitrosamines was substantially different among the reservoirs. N-Nitrosodibutylamine (NDBA), N-Nitrosopiperidine (NPIP), N-Nitrosodimethylamine (NDMA), and N-Nitrosopyrrolidine (NPYR) were abundantly present in all reservoirs. Most of N-nitrosamines except NDMA and N-nitrosodiethylamine (NDEA) were far below the generally accepted cancer risk of 10 -6 , and NDMA/NDEA were found close to the risk level (10 -6 ). Anthropogenic DOM was dominant in three reservoirs as depicted by a higher biological index (BIX) than the humification index (HIX). By the principle component analysis, BIX appeared as an indicator of N-nitrosamines (except NDEA and NPIP). A strong and direct relationship was observed between the NDMA-formation potential (FP) and concentration of total N-nitrosamines (∑NA), and BIX. These results confirmed that the anthropogenic activities were the leading source of DOM and N-nitrosamines in this city based on land-use., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Delivering drinking water with stable quality in metropolitan cities is a big challenge. This study investigated the year-long dynamics of dissolved organic matter (DOM) in the tap water and source water of a metropolitan city in southern China using fluorescence spectroscopy. The DOM detected in the tap water, and source water of Shenzhen city was season and location-dependent. A year-long cyclic trend of DOM was found with predominate protein-like fluorescence in the dry season compared to the humic-like enriched DOM in the wet season. A general DOM pattern was estimated by measuring the shift in dominant fluorescence regions on the excitation-emission matrix (EEM). The difference in fluorescent DOM (FDOM) composition (in terms of the ratio of protein-like to humic-like fluorescence) was above 200% between wet and dry seasons. The taps associated with reservoirs receiving water from the eastern tributary of Dongjiang River showed significant changes in protein-like contents than the taps with source water originating from the western part of the river. This study highlights the importance of optimizing drinking water treatment plants' operational conditions after considering seasonal changes and source water characteristics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The current investigation was designed to remove halosulfuron methyl from aqueous media by means of neem seed powder (NSP) in batch modes. Characterizations of NSP were carried out by using EDX, SEM, FTIR, point of zero charge and surface analysis. Optimum operation conditions were scrutinized by studying the influence of different factors like solution pH, dose of NSP, contact time, initial halosulfuron methyl concentration and temperature. Result indicates the dependency of the removal of halosulfuron methyl on solution pH and maximal removal (54%) was achieved in acidic medium (i.e. pH 3.0). To identify the chemical surface of NSP, point of zero charge of NSP was determined and was found to be 6.5 which imply that the surface of NSP is positively charged below pH 6.6 and favored the anionic sorption. Kinetics of halosulfuron methyl were demonstrated well by pseudo second order due to highest R 2 (0.99) owing to the nearness between experimental and calculated sorption capacities. Isotherm results imply that Langmuir was found to the principal model to explain the removal of halosulfuron methyl and maximum monolayer sorption capacity was determined to be 200 mg g -1 . Thermodynamic parameters like ΔH°, ΔG° and ΔS° were calculated from van't Hoff plot and were found negative which suggest that removal of halosulfuron methyl is exothermic and spontaneous at low temperature. These outcomes insinuate that neem seed power may be a valuable, inexpensive and ecofriendly biosorbent for the removal of pesticides.

The protection of skin cells against intense ultra-violet (UV) rays is of greater concern and needs immediate attention. Sustainable efforts and strategies are in progress to minimize the factors that adversely affect skin cells. Herein, we synthesized zinc oxide (ZnO) in the form of core-shell (Core@Shell) or reverse core-shell (RCore@Shell) structure where silica was synthesized as a shell or core, respectively on the surface of cellulose nanofiber (CNF). Both cases exhibited much higher UV-blocking performance as well as alleviate the whitening effect because these particles retain their nanoscale dimensions as favored by the cosmetic industry. Significantly, these nanostructures shows the less photocatalysis activity than that of pristine ZnO nanoparticles. And we found that the photocatalytic activity of ZnO in RCore@Shell/CNF was more suppressed that Core@Shell/CNF, showing that it is a proper structure to neutralize or scavenge free radicals prior to their exit from the particles. Our results suggest that, reduction in photocatalysis induced by Core@Shell/CNF and RCore@Shell/CNF nanostructures is a promising strategy for skincare products in cosmetic industry., Competing Interests: Declaration of competing interest There is no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Nanomaterials (NMs) have received tremendous attention as emerging adsorbents for environmental applications. The ever-increasing release into aquatic systems and the potential use in water treatment processes heighten the likelihood of the interactions of NMs with aquatic dissolved organic matter (DOM). Once DOM is adsorbed on NMs, it substantially modifies the surface properties, thus altering the fate and transport of NMs, as well as their toxic effects on (micro)organisms in natural and engineered systems. The environmental consequences of DOM-NMs interaction have been widely studied in the literature. In contrast, a comprehensive understanding of DOM-NM complexes, particularly regarding the controlling factors, is still lacking, and its significance has been largely overlooked. This gap in the knowledge mainly arises from the complex and heterogeneous structures of the DOM, which prompts the urgent need to further characterize the DOM properties to deepen the understanding associated with the adsorption processes on NMs. This review aims to provide in-depth insights into the complex DOM adsorption behavior onto NMs, whether they are metal- or carbon-based materials. First, we summarize the up-to-date analytical methods to characterize the DOM to unravel the underlying adsorption mechanisms. Second, the key DOM characteristics governing the adsorption processes are discussed. Next, the environmental factors, such as the nature of adsorbents and solution chemistry, affecting the DOM-NM interactions, are identified and discussed. Finally, future studies are recommended to fully understand the chemical traits of DOM upon its adsorption onto NMs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Drug synergy is the combine effect of drug efficacy. Synergistic combinations of active ingredients have proven to be highly effective and more useful in therapeutics. In contrast, the individual effect of drug is usually undesirable and mostly used for selecting drug-resistant mutations. Purpose of this study was to check synergistic effects of both plants (Barbadensis miller and Marsdenia condurango) against liver and cervical cancer., Methodology: Culturing of HeLa (cervical cancer cell line) and HepG2 (liver cancer cell line) cells, IC50 evaluation, viability assays (trypan blue, crystal violet), p53 ELISA and immunocytochemistry, MUSE analysis (count and viability), antioxidants (GSH, SOD, CAT), at the end RT-PCR was performed., Results: IC50 evaluation was done of each plant individually and with combination for synergistic effects, IC50 with plants combination (synergism) was applied on further viability assays (trypan blue, crystal violet, MUSE analysis via count and viability kit) p53 ELISA and immunocytochemistry for evaluation of cellular apoptosis, antioxidants assays (GSH, SOD, CAT), and RT-PCR with proliferative and apoptotic markers along with internal control., Conclusion: According to current study it was observed that synergistic effect of these plants has more anticancer properties with minimum effective dose. It was also observed that extracts possess the ability to induce apoptosis, restrict proliferation and enhanced oxidative stress.

In this study, impacts of in-situ ozonation applied directly in the membrane tank of a ceramic MBR (Oz-MBR) were assessed to elucidate its implications on micropollutant removal, microbial taxa and membrane fouling. The basic effluent quality (i.e., bulk organics and nutrients) of the MBR without and with in-situ ozonation was comparable. Importantly, pollutant-specific (10-26%) improvement in micropollutant removal was achieved by the Oz-MBR, which could be attributed to the increase in the abundance of microbial taxa responsible for the removal of structurally complex pollutants and/or ozone-assisted oxidation. In-situ ozonation affected the abundance of denitrifying bacteria and functional genes but total nitrogen removal by the Oz-MBR was comparable to that achieved by the control (C)-MBR. Improved mixed liquor properties, and the reduced accumulation of foulants on the membrane surface resulted in membrane fouling alleviation (53%) in the Oz-MBR. In addition, fouling models evaluated for the first time in the case of Oz-MBR indicated that the cake-complete model was suitable to explain membrane fouling mechanism. This comprehensive study demonstrates the performance of MBR coupled with in-situ ozonation, and the obtained results would serve as a useful reference for its implementation at pilot- and/or full-scale., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a novel coronavirus strain and the causative agent of COVID-19 was emerged in Wuhan, China, in December 2019 [1]. This pandemic situation and magnitude of suffering have led to global effort to find out effective measures for discovery of new specific drugs and vaccines to combat this deadly disease. In addition to many initiatives to develop vaccines for protective immunity against SARS-CoV-2, some of which are at various stages of clinical trials, researchers worldwide are currently using available conventional therapeutic drugs with the potential to combat the disease effectively in other viral infections and it is believed that these antiviral drugs could act as a promising immediate alternative. Remdesivir (RDV), a broad-spectrum anti-viral agent, initially developed for the treatment of Ebola virus (EBOV) and known to showed promising efficiency in in vitro and in vivo studies against SARS and MERS coronaviruses, is now being investigated against SARS-CoV-2. On May 1, 2020, The U.S. Food and Drug Administration (FDA) granted Emergency Use Authorization (EUA) for RDV to treat COVID- 19 patients [2]. A number of multicentre clinical trials are on-going to check the safety and efficacy of RDV for the treatment of COVID-19. Results of published double blind, and placebo-controlled trial on RDV against SARS-CoV-2, showed that RDV administration led to faster clinical improvement in severe COVID-19 patients compared to placebo. This review highlights the available knowledge about RDV as a therapeutic drug for coronaviruses and its preclinical and clinical trials against COVID-19., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

In this study, the effect of a high concentration of powdered activated carbon (PAC) on pollutant removal and microbial communities was systematically investigated. Micropollutant removal by the 'control' MBR (without PAC addition) was pollutant-specific and was mainly controlled by their molecular properties. The PAC-MBR achieved enhanced removal of micropollutant by 10% (ofloxacin) to 40% (caffeine). Analysis of the microbial communities in the sludge samples collected from both MBRs indicated an increase in the abundance of 24 (out of 31) genera following PAC addition. Notably, bacterial diversity enriched, particularly in the anoxic zone of the PAC-MBR, indicating a positive impact of recirculating mixed liquor containing PAC from the aerobic to the anoxic zone. In addition, PAC improved the abundance of Comamonas and Methanomethylovorans (up to 2.5%) that can degrade recalcitrant micropollutants. According to the quantitative PCR (qPCR) analysis, the copies of functional genes (nirS, nosZ and narG) increased in PAC-MBR. This study demonstrated that MBR could be operated at a high PAC concentration without compromising the pollutant removal and microbial community evolution during wastewater treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)