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Background: Single-incision laparoscopic cholecystectomy (SILC) is a minimally invasive procedure designed to minimize the number and size of the incisions needed for cholecystectomy. Titanium clips are traditionally used to close the cystic duct and artery. Although it is considered safe, dislodgement can result in bleeding and biliary leakage. Using LigaSure for duct sealing is still controversial. The aim of this study was to evaluate the safety and feasibility of using LigaSure to close the cystic duct during SILC. Methods: A prospective study over two years was conducted at the General Surgery Department, Mansoura University Hospital, on 102 patients, 51 in each group. They underwent SILC using LigaSure (Group 1) or titanium clips (Group 2) to control the cystic duct and artery. Results: The data analyzed included demographic data, operative time, intra- and postoperative complications, postoperative pain, and hospital stay. The operative time was significantly shorter in LigaSure group (68.5 ± 9.8 versus 72.9 ± 10.6 minutes in the clips group, P .03). There was no significant difference between the two groups regarding postoperative bile leak or bleeding. However, two cases in Group 1 and four cases in Group 2 were converted to multiple port laparoscopic cholecystectomy; this was statistically nonsignificant. Postoperative pain and hospital stay showed no significant difference between the two groups. Two patients in each group developed port-site incisional hernia. Conclusions: Clipless SILC using LigaSure is a feasible and safe procedure with acceptable morbidity with shorter operative time than SILC using clips. Nevertheless, the risk of port-site incisional hernia should be explained to the patients.

The present study evaluated the cardioprotective effect of astaxanthin (ASX) against isoproterenol (ISO) induced myocardial infarction in rats via the pathway of mitochondrial biogenesis as the possible molecular target of astaxanthin. The control group was injected with normal physiological saline subcutaneously for 2 days. The second group was injected with ISO at a dose of 85 mg/kg bwt subcutaneously for 2 days. The third, fourth and fifth groups were supplemented with ASX at doses of 10, 20, 30 mg/kg bwt, respectively daily by oral gavage for 21 days then injected with ISO dose of 85 mg/kg bwt subcutaneously for 2 successive days. Isoproterenol administration in rats elevated the activities of Creatine kinase-MB (CK-MB), aspartate transaminase (AST), lactate dehydrogenase (LDH), and other serum cardiac biomarkers Troponin-I activities, oxidative stress biomarkers, malondialdehyde(MDA), Nuclear factor-kappa B (NF-KB), while it decreased Peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α), Nuclear factor erythroid-2-related factor 2 (Nfe212), mitochondrial transcriptional factor A (mt TFA), mitochondrial DNA copy number and glutathione system parameters. However, Astaxanthin decreased the activities of serum AST, LDH, CK-MB, and Troponin I that elevated by ISO. In addition, it increased glutathione peroxidase and reductase activities, total glutathione and reduced GSH content, and GSH/GSSG ratio, mtDNA copy number, PGC-1α expression and Tfam expression that improved mitochondrial biogenesis while it decreased GSSG and MDA contents and NF-KB level in the cardiac tissues. This study indicated that astaxanthin relieved isoproterenol induced myocardial infarction via scavenging free radicals and reducing oxidative damage and apoptosis in cardiac tissue., (© 2024 Wiley Periodicals LLC.)

In order to protect the copper against corrosion, a novel corrosion inhibitor known as diphenyl ((2-aminoethyl) amino) (4-methoxyphenyl) methyl) phosphonate (DAMP) was developed. Acid solutions of HCl and H 2 SO 4 were the aggressive solutions employed in this study. Analysis using the FT-IR, 1 H-NMR, 31 P-NMR, 13 C-NMR and BET confirmed that the DAMP was successfully synthesized. The anti-corrosion capabilities of DAMP are evaluated using a combination of chemical, electrochemical and quantum studies. The DAMP has been found to be crucial in preventing the corrosion of copper in both HCl and H 2 SO 4 acid. This was obviously implied by the observation that the corrosion rate of copper in acid solutions decreased when DAMP was added. It is significant to note that 180 ppm produced the highest levels of inhibiting efficiency (96.6% for HCl and 95.2% for H 2 SO 4 ). The tendency of DAMP to adsorb on the surface of copper through its hetero-atoms (O, N, and P) is the main factor for the anti-corrosion capabilities of DAMP. Results from SEM/EDX tests supported this. The actual adsorption takes place via various active centers, physical and chemical mechanisms that are coordinated with the estimated quantum parameters. Additionally, the adsorption of DAMP adheres to the Langmuir isotherm., (© 2024. The Author(s).)

Background: Conversional surgery is common after laparoscopic sleeve gastrectomy (LSG) because of suboptimal weight loss (SWL) or poor responders and gastroesophageal reflux disease (GERD). Roux-en-Y gastric bypass (RYGB) is the most common conversional procedure after LSG., Methods: A retrospective cohort study analyzed patients who underwent primary RYGB (PRYGB) or conversional RYGB (CRYGB) at three specialized bariatric centers between 2008 and 2019 and tested for weight loss, resolution of GERD, food tolerance (FT), early and late complications, and the resolution of associated medical problems. This was analyzed by propensity score matching (PSM)., Results: In total, 558 (PRYGB) and 155 (CRYGB) completed at least 2 years of follow-up. After PSM, both cohorts significantly decreased BMI from baseline (p < 0.001). The CRYGB group had an initially more significant mean BMI decrease of 6.095 kg/m 2 at 6 months of follow-up (p < 0.001), while the PRYGB group had a more significant mean BMI decrease of 5.890 kg/m 2 and 8.626 kg/m 2 at 1 and 2 years, respectively (p < 0.001). Food tolerance (FT) improved significantly in the CRYGB group (p < 0.001), while CRYGB had better FT than PRYGB at 2 years (p < 0.001). A GERD resolution rate of 92.6% was recorded in the CRYGB (p < 0.001). Both cohorts had comparable rates of early complications (p = 0.584), late complications (p = 0.495), and reoperations (p = 0.398). Associated medical problems at 2 years significantly improved in both cohorts (p < 0.001)., Conclusions: CRYGB is a safe and efficient option in non- or poor responders after LSG, with significant weight loss and improvement in GERD. Moreover, PRYGB and CRYGB had comparable complications, reoperations, and associated medical problem resolution rates., (© 2024. The Author(s).)

Antibacterial compounds that reduce extracellular polymeric substances (EPS) are needed to avoid bacterial biofilms in water pipelines. Herein, green one-pot synthesis of α-aminophosphonates (α-Amp s ) [A-G] was achieved by using ionic liquid (IL) as a Lewis acid catalyst. The synthesized α-Amp analogues were tested against different bacteria such as Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa. The representative [B] analogue showed an efficient antibacterial effect with MIC values of 3.13 μg/mL for E. coli, P. aeruginosa, and 6.25 μg/mL for B. subtilis. Additionally, a strong ability to eliminate the mature bacterial biofilm, with super-MIC values of 12.5 μg/mL for E. coli, P. aeruginosa, and 25 μg/mL for B. subtilis. Moreover, bacterial cell disruption by ROS formation was also tested, and the compound [B] revealed the highest ROS level compared to other compounds and the control, and efficiently destroyed the extracellular polymeric substances (EPS). The docking study confirmed strong interactions between [B] analogue and protein structures with a binding affinity of -6.65 kCal/mol for the lyase protein of gram-positive bacteria and -6.46 kCal/mol for DNA gyrase of gram-negative bacteria. The results showed that α-Amp s moiety is a promising candidate for developing novel antibacterial and anti-biofilm agents for clean water supply., 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.)

Background: The incidence of Antimicrobial Resistance (AMR) in uropathogens varies between countries and over time. We aim to study the patterns and potential predictors of AMR among patients with UTIs admitted to the Urology Department at Alexandria University Hospital., Methods: An observational retrospective record-based study was conducted on all patients admitted to the Urology department from October 2018 to October 2020. Data collected from patients' records included: demographic data, diagnosis on admission, history of chronic diseases, duration of hospital stay, insertion of a urinary catheter, duration of the catheter in days, history of the use of antibiotics in the previous three months, and history of urinary tract operations. If UTI was documented, we abstracted data about urine culture, use of antibiotics, results of urine cultures, type of organism isolated, and sensitivity to antibiotics. We conducted a multivariable logistic regression model. We performed Classification and Regression Tree Analysis (CART) for predicting risk factors associated with drug resistance among patients with UTI. Data were analyzed using SPSS statistical package, Version 28.0, and R software (2022)., Results: This study encompassed 469 patients with UTIs. The most commonly isolated bacterium was Escherichia coli, followed by Klebsiella pneumoniae. Multidrug resistance (MDR) was found in 67.7% (149/220) of patients with hospital-acquired UTIs and in 49.4% (83/168) of patients with community-acquired UTIs. Risk factors independently associated with antimicrobial resistance according to logistic regression analysis were the use of antibiotics within three months (AOR = 5.2, 95% CI 2.19-12.31), hospital-acquired UTI (AOR = 5.7, 95% CI 3.06-10.76), diabetes mellitus (AOR = 3.8, 95% CI 1.24-11.84), age over 60 years (AOR = 2.9, 95% CI 1.27-6.72), and recurrent UTI (AOR = 2.6, 95% CI 1.08-6.20). Classification and regression tree (CART) analysis revealed that antibiotic use in the previous three months was the most significant predictor for developing drug resistance., Conclusion: The study concluded a high level of antimicrobial resistance as well as significant MDR predictors among hospitalized patients with UTIs. It is vital to assess resistance patterns in our hospitals frequently to improve rational antibiotic treatment as well as to sustain antimicrobial stewardship programs and a rational strategy in the use of antibiotics. Empirical therapy for UTI treatment should be tailored to the potential pathogens' susceptibility to ensure optimal treatment. Strategic antibiotic use is essential to prevent further AMR increases. Further research should focus on suggesting new biological systems or designed drugs to combat the resistance of UTI pathogens., (© 2024. The Author(s).)

A series of new coumarin-N-heterocyclic hybrids, coumarin-quinolines 7a-e, coumarin-acridines 10b,c and coumarin-neocryptolepines 13b,c were synthesized and evaluated for their anticancer and antimicrobial activities. The structures of all synthesized hybrids were confirmed by FT-IR, 1 H-NMR, 13 C-NMR, and MS spectrometry. The anti-proliferative activity of hybrids 7a-e, 10c and 13c were bio-evaluated using MTT-assay against colon (CaCo-2), lung (A549), breast (MDA-MB-231), and hepatocellular carcinoma (HepG-2) human cancer cell lines using doxorubicin as a reference drug. The results demonstrated that, all hybrids displayed moderate to good anti-proliferative activity against the cell lines. The most active hybrids were 7a-d and 10c against CaCo-2 cancer cell line with IC 50 : 57.1, 52.78, 57.29, 51.95 and 56.74 µM, and selectivity index 1.38, 1.76, 2.6, 1.96 and 0.77; respectively. While, 7a,d were potent against A549 cancer cell line with IC 50 : 51.72, 54.8 µM and selectivity index 1.5, 0.67; respectively. Moreover, 7c showed the most potency against MDA-MB-231 cancer cell line with IC 50 : 50.96 µM and selectivity index 2.20. Interestingly, docking results revealed that binding energy of the current compounds showed marked affinity values ranging from -6.54 to -5.56 kcal with interactions with the reported key amino acid SER 79. Furthermore, the antimicrobial activity of the synthesized hybrids 7a-e, 10b,c, 13b and 13c were evaluated against Gram-positive and Gram-negative bacterial and fungal strains. The hybrids 10b, 13b, 10c, and 13c exhibited broad-spectrum antibacterial activity against E.coli, S. mutans, and S. aureus with MIC from 3.2 to 66 µM, this hybrids also displayed antifungal activity against C. albicans with MIC values ranging from 0.0011 to 29.5 µM. In-silico investigation of the pharmacokinetic properties indicated that tested hybrids had high GI absorption, low Blood Brain Barrier (BBB) permeability in addition to cell membrane penetrability., (© 2023. The Author(s).)

Objective: The limitations faced by conventional drug delivery systems are being overcome through the use of rapidly evolving cancer nanotherapeutics. Determining the manner in which the Ehrlich solid tumor (EST) is impacted by the new bioactive Alanda-loaded flax seed gum nanoparticles (Alanda NPs) functioning as an anti-carcinogenic agent represents the research objective of this paper., Materials and Methods: Identification of the functional groups, surface morphology, particle size, and zeta potential were among the characterizations and preparations made for the prepared nanoparticles. A Control group, a Flax Seed Gum group, a raw Alanda group, an Alanda NPs group, an EST group, and an induced EST treated with Alanda NPs group comprised the six groups respectively which the 60 female mice were separated into in this in vivo study., Results: Toxicity assessments for kidneys and liver were performed alongside the detection of total genomic DNA degradation. The zeta potential and the particle sizes for Alanda NPs were -25.60±0.38 mv and 40±0.28 nm, respectively, where the latter demonstrated a monodisperse spherical shape, per the findings. The use of Alanda NPs to treat EST was found to alle te the DNA damage, apoptosis, and renal and hepatic toxicity that EST induces. Additionally, the activation of oxidative stress and apoptosis causing the renal and hepatic toxicity induced by EST is counteracted by the scavenging of free radicals by the Alanda NPs., Conclusions: A high degree of safety for effective cancer treatment was displayed by the newly developed oral nanoparticles while also demonstrating strong potential in vivo.

Nasopharyngeal carcinoma (NPC), a rare head and neck malignancy, arises from the epithelial lining of nasopharyngeal mucosa. The confluence of various risk factors, such as latent Epstein-Barr virus infection, genetic susceptibility, smoking, alcohol consumption, and high nitrosamine diet, is thought to contribute to NPC pathogenesis. Radiation therapy serves as the mainstay of treatment for early stage while concurrent chemotherapy and radiation are the basis of treatment for locoregional advanced disease with overall 80% five-year survival rate. Recurrent or metastatic disease pose treatment challenges as reirradiation, repeat cycles of chemotherapy, and surgery follow with high likelihood of treatment toxicity or postoperative morbidities. Typically reserved for nonresectable recurrent or metastatic disease, immunotherapy serves as novel treatment for NPC. NPC tumor microenvironment predominated by a dense infiltrate of immune cells hosts an ideal target for immunotherapy. Several clinical trials have investigated the efficacy of anti-programmed cell death protein 1 antibodies such as pembrolizumab, nivolumab, and camrelizumab with promising results. Treatment of recurrent and metastatic NPC remains a challenge; however, the advent of immunotherapy has provided additional options and potential for preventative and therapeutic measures., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Microbial infection is the most common obstacle in the wound healing process, leading to wound healing impairment and complications and ultimately increasing morbidity and mortality. Due to the rising number of pathogens evolving resistance to the existing antibiotics used for wound care, alternative approaches are urgently required. In this study, α-aminophosphonate derivatives as antimicrobial agents were synthesized and incorporated into self-crosslinked tri-component cryogels composed of fully hydrolyzed polyvinyl alcohol (PVA-F), partially hydrolyzed polyvinyl alcohol (PVA-P), and cellulose nanofibrils (CNFs). Initially, the antimicrobial activity of four α-aminophosphonate derivatives against selected skin bacterial species was tested and their minimum inhibitory concentration was determined based on which the most effective compound was loaded into the cryogels. Next, the physical and mechanical properties of cryogels with various blending ratios of PVA-P/PVA-F and fixed amounts of CNFs were assessed, and drug release profiles and biological activities of drug-loaded cryogels were analyzed. Assessment of α-aminophosphonate derivatives showed the highest efficacy of a cinnamaldehyde-based derivative (Cinnam) against both Gram-negative and Gram-positive bacteria compared to other derivatives. The physical and mechanical properties of cryogels showed that PVA-P/PVA-F with a 50/50 blending ratio had the highest swelling ratio (1600%), surface area (523 m 2 g -1 ), and compression recoverability (72%) compared to that with other blending ratios. Finally, antimicrobial and biofilm development studies showed that the cryogel loaded with a Cinnam amount of 2 mg (relative to polymer weight) showed the most sustained drug release profile over 75 h and had the highest efficacy against Gram-negative and Gram-positive bacteria. In conclusion, self-crosslinked tri-component cryogels loaded with the synthesized α-aminophosphonate derivative, having both antimicrobial and anti-biofilm formation properties, can have a significant impact on the management of uprising wound infection.

This work describes the synthesis of quinoline-based N --heterocyclic arenes and their biological evaluation as molluscicides against adult Biomophalaria alexandrina snails as well as larvicides against Schistosoma mansoni larvae (miracidia and cercariae). Molecular docking studies were demonstrated to investigate their affinity for cysteine protease protein as an interesting target for antiparasitics. Compound AEAN showed the best docking results followed by APAN in comparison to the co-crystallized ligand D1R reflected by their binding affinities and RMSD values. The egg production, hatchability of B. alexandrina snails and ultrastructural topography of S. mansoni cercariae using SEM were assessed. Biological evaluations (hatchability and egg-laying capacity) revealed that the quinoline hydrochloride salt CAAQ was the most effective compound against adult B. alexandrina snails, whereas the indolo-quinoline derivative APAN had the most efficiency against miracidia, and the acridinyl derivative AEAA was the most effective against cercariae and caused 100% mortality. CAAQ and AEAA were found to modulate the biological responses of B. alexandrina snails with/without S. mansoni infection and larval stages that will affect S. mansoni infection. AEAA caused deleterious morphological effects on cercariae. CAAQ caused inhibition in the number of eggs/snail/week and reduced reproductive rate to 43.8% in all the experimental groups. CAAQ and AEAA can be recommended as an effective molluscicide of plant origin for the control program of schistosomiasis.

Background: One-stage revision Roux-en-Y gastric bypass (RRYGB) after Laparoscopic adjustable gastric banding (LAGB) is widely adopted, but its safety is still debated., Objective: This study aimed to compare outcomes between primary Roux-en-Y gastric bypass (PRYGB and RRYGB after LAGB., Method: A retrospective record-based cohort study of patients who underwent PRYGB and RRYGB for failed LAGB and completed at least 2 years of follow-up from 2008 to 2019. Propensity score matching (PSM) analysis was conducted to obtain a balanced sample of patients with RRYGB and PRYGB interventions by adjusting for baseline covariates including age and sex., Results: Patients with PRYGB (n = 558) and RRYGB (n = 156) were included. PSM identified 98 patients for RRYGB and 98 patients for PRYGB. Both cohorts exhibited significant reductions in BMI compared to baseline values (p < 0.001), but reductions were significantly higher in PRYGB compared to those in RRGYB at 6 months (- 10.55 ± 8.54 vs. - 8.38 ± 5.07; p = 0.032), 1-year (- 21.50 ± 8.19 vs. 16.14 ± 6.93; p < 0.001), and 2 years (- 24.02 ± 7.85 vs. - 18.93 ± 6.80; p < 0.001), respectively. A significant improvement in food tolerance from the 1st to the 2nd year was seen after RYGB (p < 0.001). The rates of early and late complications were similar in both cohorts (p = 0.537, p = 1.00). Overall re-intervention rates were 5.1 and 3.1% for RRYGB and PRYGB p = 0.721). Both cohorts exhibited significant improvement in comorbidities after 2 years (p < 0.001)., Conclusions: One-stage RRYGB for failed LAGB is safe and effective with comparable rates of complications, re-interventions, and resolution of associated comorbid conditions compared to PRYGB., (© 2022. The Author(s).)

Background: Sleeve dilatation after laparoscopic sleeve gastrectomy (LSG) causes weight regain (WR). Banded sleeve gastrectomy (BSG) was proposed to prevent dilatation and reduce WR., Methods: A retrospective cohort study on patients who underwent BSG and LSG and completed 4 years of follow-up from 2016 to 2021 was included. Body mass index (BMI), percentage of excess weight loss (%EWL), percentage of total weight loss (%TWL), and FT scores were calculated at 1, 2, 3, and 4 years. The sleeve volume was estimated at 6 months, 1 year, and 4 years. Multi-variate analysis was conducted to assess correlations between covariates. WR was calculated as weight gain > 10%, > 10 kg above the nadir, or BMI increase of ≥ 5 kg/m 2 above the nadir., Results: This study included LSG 1279 patients and BSG 132 patients. Mean %EWL at 1 year was 83.87 ± 17.25% in LSG vs. 85.71 ± 7.92% in BSG and was 83.47 ± 18.87% in LSG and 85.54 ± 7.48% in BSG at 4 years. Both had significant weight loss over time (p. < 0.001) with no significant main effect of surgery (p.0.438). Mean sleeve volume at 6 months was 102.32 ± 9.88 ± 10.28 ml in LSG vs. 101.89 ± 10.019 ml in BSG and at 4 years was 580.25 ± 112.25 ml in LSG vs. 157.94 ± 12.54 ml in BSG (p. < 0.001). WR occurred in 136 (10.6%) and 4 (3.1%) (p.0.002) in LSG and BSG patients, 90 (7%) vs. zero (0%) (p.0.002) and 31 (2.4%) vs. zero (0%) (p.0.07) using the > 10%, > 10 kg increase above the nadir and the ≥ 5 kg/m 2 BMI increases above the nadir formulas, respectively., Conclusion: BSG had significantly lower sleeve volume, significantly lower WR, and significantly lower FT scores than LSG after 4 years from surgery; however, volume changes were not correlated with weight loss., (© 2022. The Author(s).)

Background: Hepatocellular carcinoma (HCC) is the most common histologic type of primary liver cancers worldwide. Hepatitis C virus (HCV) infection remains a major risk factor for chronic liver disease, cirrhosis, and HCC. To understand the molecular pathogenesis of HCC in chronic HCV infection, many molecular markers are extensively studied, including long noncoding RNAs (lncRNA). Objective: To evaluate the expression levels of lncRNAs (LINC01564, RAMS11), CBX4, and TOP2A in patients with chronic HCV infection and patients with HCC on top of chronic HCV infection and correlate these levels with the clinicopathological features of HCC. Subjects and Methods: One hundred and fifty subjects were enrolled in this study and divided into three groups: group I included 50 patients with HCC on top of chronic hepatitis C (CHC), group II included 50 patients with CHC only, and group III included 50 healthy individuals as a control group. LncRNAs relative expression level was determined by RT-PCR. Results: lncRNA (LINC01564, RAMS11), CBX4, and TOP2A relative expression levels were upregulated in both patient groups compared to controls (p < 0.001*), with the highest levels in the HCC group compared with the CHC group. Additionally, these levels were significantly positively correlated with the clinicopathological features of HCC. Conclusions: The lncRNA (LINC01564, RAMS11), CBX4, and TOP2A relative expression levels were upregulated in CHC patients—in particular, patients with HCC. Thus, these circulatory lncRNAs may be able to serve as promising noninvasive diagnostic markers for HCC associated with viral C hepatitis.

A series of novel neocryptolepine-rhodanine hybrids ( 9a,b , 11a - d , 14 , and 16a,b ) have been synthesized by combining neocryptolepine core 5 modified at the C-11 position with rhodanine condensed with the appropriate aryl/hetero aryl aldehydes. Based on these findings, the structures of the hybrids were confirmed by spectral analyses. By employing the MTT assay, all hybrids were tested for their in vitro antiproliferative activity against two cancer cell lines, including MDA-MB-231 (human breast) and HepG-2 (hepatocellular carcinoma). Interestingly, the IC 50 values of all hybrids except 9b and 11c showed activity comparable to the standard anticancer drug, 5-fluorouracil, against HepG-2 cancer cells. Furthermore, the cytotoxicity of all the synthesized hybrids was investigated on a normal skin human cell line (BJ-1), and the results showed that these compounds had no significant cytotoxicity toward these healthy cells at the highest concentration used in this study. This study also indicated that the active hybrids exert their cytotoxic activity via the induction of apoptosis. A molecular docking study was used to shed light on the molecular mechanism of their anticancer activity. The docking results revealed that the hybrids exert their mode of action through DNA intercalation. Furthermore, in silico assessment for pharmacokinetic properties was performed on the most potent compounds, which revealed candidates with good bioavailability, high tolerability with cell membranes, and positive drug-likeness values.

Fighting external pathogens relies on the tight regulation of the gene expression of the immune system. Ferroptosis, which is a distinct form of programmed cell death driven by iron, is involved in the enhancement of follicular helper T cell function during infection. The regulation of RNA is a key step in final gene expression. The present study aimed to identify the expression level of antisense lncRNAs (A2M-AS1, DBH-AS1, FLVCR1-DT, and NCBP2AS2-1) and FLVCR1 in COVID-19 patients and its relation to the severity of the disease. COVID-19 patients as well as age and gender-matched healthy controls were enrolled in this study. The expression level of the antisense lncRNAs was measured by RT-PCR. Results revealed the decreased expression of A2M-AS1 and FLVCR1 in COVID-19 patients. Additionally, they showed the increased expression of DBH-AS1, FLVCR1-DT, and NCBP2AS2. Both FLVCR1-DT and NCBP2AS2 showed a positive correlation with interleukin-6 (IL-6). DBH-AS1 and FLVCR1-DT had a significant association with mortality, complications, and mechanical ventilation. A significant negative correlation was found between A2M-AS1 and NCBP2AS2-1 and between FLVCR1 and FLVCR1-DT. The study confirmed that the expression level of the antisense lncRNAs was deregulated in COVID-19 patients and correlated with the severity of COVID-19, and that it may have possible roles in the pathogenesis of this disease.

Herein, efficient and potential chelating α-aminophosphonate based sorbents (AP-) derived from three different amine origins (aniline/anthranilic acid/O-phenylenediamine) to form AP-H, carboxylated and aminated enhanced aminophosphonate as AP-H, AP-COOH, and AP-NH 2 were synthesized via a facile method. The structure of the synthesized sorbents was elucidated using different techniques; elemental analysis (CHNP/O), FT-IR, NMR ( 1 H-, 13 C and 31 P NMR), TGA and BET. The fabricated sorbents were exploited for Hg(II) removal from aqueous solution via sorption properties. Isotherm fitted by Langmuir equation: the maximum sorption capacities at optimum pH 5.5, and T:25 ± 1 °C, were found to be 1.33, 1.23, and 1.15 mmol Hg g -1 for AP-COOH, AP-NH 2 , AP-H, respectively, which is roughly correlated with the active sites density and the hard/soft characteristics of adsorbents' reactive groups. Metal-ligand binding affinities are qualitatively rationalized in terms of hard and soft acids and bases (HSAB) theory. The interaction of Hg(II) (soft) has a stronger affinity to AP-COOH can be considered a softer base compared with reference material (AP-H) over than AP-NH 2 (hard). This sequence result showed opposite trends consistent with their reciprocal properties according to the steric effect modulates and the specific surface area. Thermodynamics analysis for absolute values of ΔH°, ΔS° and ΔG° afford the selectivity towards Hg(II) sorption with the following order: AP-COOH > AP-NH 2 >AP-H. Elution and regeneration was carried out by HCl solution and recycled for a minimum of five cycles, the sorption and desorption efficiencies are greater than 91%. Such sorbents exhibit good durability, stability and promising potential for Hg(II) removal. Finally, a new modelling technique for quantitative non-linear description and comparison of equivalent geographical positions in 3D space of extended relationships. Exothermic and spontaneous behavior were observed using a proposed Floatotherm that included the Van't Hoff parameters model., (Copyright © 2022. Published by Elsevier Ltd.)

Environmentally-friendly, cyanidin(Cy)-based anthocyanin isolated from red-cabbage served as a spectroscopic probe imprinted onto chitosan nanoparticles (CsNPs), which were in turn integrated onto cellulose paper strip (CPS) as a host matrix to develop a metallochromic solid state sensor for real-time selective determination of ferric ions in an aqueous medium. The ferric transition metal ions in aqueous environments were detected using a novel, simple, portable, fast responsive, low-cost, real-time, environmentally safe, reversible and colorimetric sensor based on chitosan nanoparticles as a hosting biopolymer and cyanidin phenol chromophore as a biomolecular probe. In order to use the cyanidin biomolecule as a pH indicator and chelating agent, it was purified from red-cabbage and added into the CsNPs biosensor film. The colorimetric shift increased in direct proportion to the ferric ion concentration. As a result, the current research that was both qualitative and quantitative was carried out. While the Cy-CsNPs-CPS sensor showed high selectivity for ferric ions, no color change was detected for other metal cations. It was discovered that the detection process occurred as a result of a coordination complex formed between the active sites of phenolic cyanidin and Fe(III) ions., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Minimal evidence exists on the efficacy of different digital manufacturing techniques in the fabrication of precise dental working models and provisional prosthesis. Aim of study: The objective was to evaluate the effect of two digital fabrication techniques (CAD/CAM milling and 3D printing) on the accuracy of PMMA working models and marginal fit of PMMA provisional prosthesis. Materials and methods: Two abutment teeth of modified typodont were prepared. A reference stone model was fabricated, and an optical impression was performed to obtain a CAD reference model. Four CAM milled working models and four printed working models were fabricated. CAD software was used to design the provisional prostheses. Group A tested four milled provisional prosthesis, and group B tested four 3D printed prosthesis. The 3D accuracy of working models was assessed by superimposition of the control reference working model on the CAD test working model. A stereo-optical microscope was used to assess vertical marginal fit of the provisional dental prosthesis. Student's t and Mann-Whitney U tests were utilized to compare the two groups. Results: Results showed no statistically significant difference between the two tested groups. Conclusion: The two digital working model fabrication techniques recorded comparable accuracy. Similarly, 3D printed provisional prosthesis showed comparable marginal fit to the CAD/CAM milled ones.

The naturally occurring neocryptolepine (5-Methylindolo [2,3- b ]quinoline) and its analogs exhibited prominent anticancer and antimalarial activity. However, the main problem of this class of compounds is their poor aqueous solubility, hampering their bioavailability and preventing their clinical development. To overcome the problem of insolubility and to improve the physicochemical and the pharmacological properties of 5-Methylindolo [2,3- b ]quinoline compounds, this work was designed to encapsulate such efficient medical compounds into mesoporous silica oxide nanoemulsion (SiO 2 NPs). Thus, in this study, SiO 2 NPs was loaded with three different concentrations (0.2 g, 0.3, and 0.6 g) of 7b (denoted as NPA). The findings illustrated that the nanoparticles were formed with a spherical shape and exhibited small size (less than 500 nm) using a high concentration of the synthesized chemical compound (NPA, 0.6 g) and good stabilization against agglomeration (more than -30 mv). In addition, NPA-loaded SiO 2 NPs had no phase separation as observed by our naked eyes even after 30 days. The findings also revealed that the fabricated SiO 2 NPs could sustain the release of NPA at two different pH levels, 4.5 and 7.4. Additionally, the cell viability of the produced nanoemulsion system loaded with different concentrations of NPA was greater than SiO 2 NPs without loading, affirming that NPA had a positive impact on increasing the safety and cell viability of the whole nanoemulsion. Based on these obtained promising data, it can be considered that the prepared NPA-loaded SiO 2 NPs seem to have the potential for use as an effective anticancer drug nanosystem.

DNA gyrase and topoisomerase IV are proven to be validated targets in the design of novel antibacterial drugs. In this study, we report the antibacterial evaluation and molecular docking studies of previously synthesized two series of cyclic diphenylphosphonates ( 1a - e and 2a - e ) as DNA gyrase inhibitors. The synthesized compounds were screened for their activity (antibacterial and DNA gyrase inhibition) against ciprofloxacin-resistant E.coli and Klebsiella pneumoniae clinical isolates having mutations (deletion and substitution) in QRDR region of DNA gyrase. The target compound ( 2a ) that exhibited the most potent activity against ciprofloxacin Gram-negative clinical isolates was selected to screen its inhibitory activity against DNA gyrase displayed IC 50 of 12.03 µM. In addition, a docking study was performed with inhibitor ( 2a ), to illustrate its binding mode in the active site of DNA gyrase and the results were compatible with the observed inhibitory potency. Furthermore, the docking study revealed that the binding of inhibitor ( 2a ) to DNA gyrase is mediated and modulated by divalent Mg 2+ at good binding energy (-9.08 Kcal/mol). Moreover, structure-activity relationships (SARs) demonstrated that the combination of hydrazinyl moiety in conjunction with the cyclic diphenylphosphonate based scaffold resulted in an optimized molecule that inhibited the bacterial DNA gyrase by its detectable effect in vitro on gyrase-catalyzed DNA supercoiling activity.

Purpose of the Study: We explored potential predictive variables associated with outcomes using baseline clinical parameters of 500 hospitalised patients with COVID -19 in a single centre, UK., Methods: Retrospective study collecting demographic and clinical characteristics of patients admitted at Southend University Hospital from 20th February to 7th May 2020., Results: The mean age of the cohort admitted to hospital with Covid-19 was 69.4 and 58% were over 70. Comorbidities were more frequently observed in non-survivors, whose mean Clinical Frailty Scale was significantly higher (5 vs 3) than survivors, p < 0.001. In addition, mean C-reactive protein was significantly higher., Conclusion: Older and frailer patients with high inflammatory markers were at risk of poor outcomes. Integrated frailty and age-based risk stratification is essential, in addition to monitoring saturation /FiO2 ratio (SFR) and inflammatory markers throughout the disease course to allow for early intervention to improve patient outcomes. A frailty-based risk-stratification approach, rather than age may prove more valuable when considering interventions in patients with multiple comorbidities., (© 2021. European Geriatric Medicine Society.)

Objective: to synthesize evidence about the efficacy of electronic cigarettes versus Nicotine Replacement Therapy and placebo to quit smoking., Data Sources: We searched for clinical trials with no publication date restriction until December 2019. The search included CENTRAL, MEDLINE, PsycINFO, Science Direct, Center for reviews and dissemination and HTA database and Trip database, clinical trials registries, gray literature and examined the references of relevant articles., Inclusion and Exclusion Criteria: Two review authors independently checked the titles and abstracts then the full text of initial hits. Main outcomes were sustained continuous abstinence rate, 7-day point prevalence abstinence rate, sustained reduction of 50% or greater in baseline cigarette consumption and adverse effects., Data Extraction and Synthesis: Two review authors independently extracted data and assessed risk of bias using the Cochrane RoB 2 tool. We conducted a random-effects model through the Mantel-Haenszel method., Results: We retrieved 12 trials involving 9863 participants. CO- validated 1-month continuous abstinence rate improved by 33% in the e-cigarettes group (range 6-66%, moderate evidence). We are uncertain if e-cigarettess influence continuous abstinence rate at 3-, 6- and 12 months as well as sustained reduction of 50% or greater in baseline cigarette consumption at different follow-up periods. One study of 884 participants displayed improved 12-month 7-day point abstinence by 46% (range 17%-82%). E-cigarettes may increase or do not affect the proportion of serious adverse effect at 6 and 12 months follow up., Conclusion: Very low certainty evidence supported e-cigarettess to help quit smoking in the short term. There is not enough evidence to determine if e-cigarettess are a safe and efficacious means of smoking cessation in the long term (12+ months).

Neocryptolepine (5-methyl-5H-indolo[2,3-b] quinoline) analogs were synthesized and evaluated in vitro and in vivo for their effect versus Ehrlich ascites carcinoma (EAC). The analogs showed stronger cytotoxic activity against EAC cells than the reference drug. The in vivo evaluation of the target compounds against EAC-induced solid tumor in the female albino Swiss mice revealed a remarkable decrease in the tumor volume (TV) and hepatic lipid peroxidation. A noticeable increase of both superoxide dismutase (SOD) and catalase (CAT) levels was reported ( p < 0.001), which set-forth proof of their antioxidant effect. In addition, the in vitro antioxidant activity of the neocryptolepine analogs was screened out using the DPPH method and showed promising activities activity. The histopathological investigations affirmed that the tested analogs have a remarkable curative effect on solid tumors with minimal side-effect on the liver. The study also includes illustrated mechanism of the antitumor activity at the cell level by flow cytometry. The cell cycle analysis showed that the neocryptolepine analogs extensively increase the aggregation of tumor cells in three phases of the cell cycle (G0/G1, S and G2/M) with the emergence of a hypo-diploid DNA content peak (sub-G1) in the cell cycle experiments, which is a clear-cut for the apoptotic cell population. Furthermore, the immunological study manifested a significant elevation in splenic lymphocyte count ( p < 0.001) with the elevation of the responsiveness of lymphocytes to phytohemagglutinin (PHA). These results indicate that these naturally-based neocryptolepine alkaloids exhibit marked antitumor activity in vivo and represent an important lead in the development of natural-based anticancer drugs.

Novel α-aminophosphonates 4 were synthesized via one pot three-component reaction of 4-aminoantipyrine, aldehydes, triphenylphosphite and Lewis acid catalyst. The chemical structures of all the synthesized compounds were elucidated by IR, NMR and MS spectral analysis. The antimicrobial activity of 4 was tested in vitro against pathogenic microbes such as E.coli, S.aureus, A.niger and C.albicans. Three of them (4f-h) exhibited high antimicrobial activity and were loaded to carrageenan cryogel for drug delivery studies. With the aid of cellulose nanofibrils (CNF) as reinforcing material and glyoxal as a cross-linking agent, porous cryogels with improved mechanical properties were obtained. Among all, CAR-7 presents the optimum cryogel sample, which contained around 16% CNF and 0.2 mL/15 mL polymer blend. CAR-7 demonstrated highest mechanical compressive strength, porosity (80%), and swelling capacity (75%). Sustainable release behavior over 24 h was observed for the loaded cryogels. The antimicrobial activity of cryogels against S.aureus showed marginal differences between samples. CAR-9 (loaded with 4f) showed the highest reduction percentage in number of bacterial colonies (99.94%) followed by CAR-11 (loaded with 4h, 99.3%) and finally CAR-10 (loaded with 4g, 99.29%)., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Pyrazolines show different biological activities. In recent years, interest in the chemistry of hydrazonoyl halides has been renewed. 1,3,4-Thiadiazoles are one of the most common heterocyclic pharmacophores with a wide range of biological activities., Results: Ethyl 2-(5-(furan-2-yl)-3-( p -tolyl)-4,5-dihydro-1 H -pyrazol-1-yl)-4-methyl-thiazole-5-carboxylate, 2-(5-(furan-2-yl)-3-( p -tolyl)-4,5-dihydro-1 H -pyrazol-1-yl)thiazol-4(5 H )-one, and 1-(2-(5-(furan-2-yl)-3-( p -tolyl)-4,5-dihydro-1 H -pyrazol-1-yl)-4-methylthiazol-5-yl)ethan-1-one were synthesized from the reaction of 5-(furan-2-yl)-3-( p -tolyl)-4,5-dihydro-1 H -pyrazole-1-carbothioamide with different halogenated compounds. Thiazole, 1,3,4-thiadiazole and pyrano[2,3- d ]thiazole derivatives were also synthesized. The structures of the newly synthesized compounds were elucidated based on elemental analysis, spectral data, and alternative synthetic routes whenever possible. Additionally, the newly synthesized compounds were screened for antimicrobial activity against various microorganisms., Conclusions: A new series of novel functionalized 1,3,4-thiadiazoles, 1,3-thiazoles, and pyrazoline-containing moieties were synthesized using hydrazonoyl halides as precursors and evaluated for their in vitro antibacterial, and antifungal activities. The antimicrobial results of the examined compounds revealed promising results and some derivatives have activities similar to the references used., Competing Interests: The authors declare that they have no competing interests.

A novel series of 1,3,4-thiadiazoles, 5-arylazothiazoles and hexahydropyrimido-[4,5-d][1,2,4]triazolo[4,3-a]pyrimidines were synthesized via reaction of hydrazonoyl halides with each of alkyl carbothioates, carbothioamides and 7-thioxo-5,6,7,8-tetrahydropyrimido-[4,5-d]pyrimidine-2,4(1H,3H)-diones in the presence of triethylamine. The structures of the newly synthesized compounds were established based on their spectral data, elemental analyses and alternative synthetic routes whenever possible. Also, the newly synthesized compounds were screened for their antimicrobial activity against various microorganisms.