Inhibition Capability Research Articles

Evaluations of Polyacrylamide Water-Based Drilling Fluids for Horizontal Drilling in the Shaly Wolfcamp Formation

Summary The Permian Basin, located in southeastern New Mexico and west Texas, is treated as the largest province of oil and gas production in the United States (US). The majority of hydrocarbon production from the Permian Basin is from the Wolfcamp shaly formation. Drilling horizontal and extended reached wells is continuously increasing day after day in the Permian Basin. Oil-based mud (OBM) is used to drill these horizontal wells for enhancing shale inhibition, reducing torque and drag, and supporting thermal stability of mud rheology. Due to environmental regulation for limiting use of OBM, the petroleum industry has tried to develop water-based fluid (WBF) that approaches the performance advantages of OBM. The main objective of this research is to formulate and develop WBF by using polyacrylamide anionic friction reducer (AFR) for drilling the lateral sections of horizontal wells in the shaly Wolfcamp formation. Shale inhibition, barite sagging, lubricity, and thermal stability of the formulated WBF with AFR will be studied to evaluate the developed WBF. Laboratory experiments were conducted to develop and evaluate the performance of the formulated WBF with AFR. The shale inhibition capabilities of the developed WBF with AFR were evaluated by using zeta potential, shale dispersion test, and immersion test. The results prove the capability of the formulated WBF with AFR to prevent both shale swelling and shale dispersion. AFR limits water penetrations to shale through encapsulation. The mixing procedures of AFR with WBF affect both the thermal stability of mud rheology and shale inhibition. Adding AFR to WBF helps to suspend weighting materials and mitigate barite sag. Besides, AFR decreases torque and drag by decreasing the coefficient of friction (COF). Furthermore, AFR supports enhanced stability of mud rheology with time up to 14 days at temperatures up to 180°F. The formulated WBF with AFR can be used for enhancing shale inhibition, supporting thermal and time stability of fluid rheology, improving lubricity, and minimizing barite sagging for drilling shaly Wolfcamp formations. This study presents a promising WBF to replace OBM to drill lateral sections in the Permian Basin.

Release and MMP-9 Inhibition Assessment of Dental Adhesive Modified with EGCG-Encapsulated Halloysite Nanotubes

Degradation of the collagen fibrils at the dentin-resin interface by the enzymatic activity of matrix metalloproteinases (MMPs) has been known to permit some dental restoration complications, such as microleakage, secondary caries, and, ultimately, restoration failures. This study aimed to evaluate a modified adhesive by adding an MMP inhibitor from green tea extract with and without nanotube encapsulation to sustain the drug release. Epigallocatechin-3-gallate (EGCG) and Halloysite nanotubes (HNTs) were prepared to produce three variant combinations of modified adhesive (EGCG, EGCG-encapsulated HNT, and EGCG-free HNT). The drug loading efficiency and EGCG release over time were evaluated using UV-vis spectrometry. MMP-mediated β-casein (BCN) cleavage rate assays were used to determine the ability of the EGCG in eluates of the adhesive to inhibit MMP-9 activities. For up to 8 weeks, HNT encapsulation reduced release to a statistically significant level. MMP-mediated β-casein cleavage rate assays showed a significant decrease for the EGCG groups compared to the non-EGCG adhesive groups. Furthermore, the use of HNT for EGCG encapsulation to modify a dental adhesive helped slow down the rate of EGCG release without impacting its MMP inhibitory capabilities, which may help to maintain the dentin-resin interface's integrity over the long term after dental restoration placement.

Corrosion inhibition properties of Camellia chrysantha flower extract for Q235 in 1 M HCl solution

The inhibition capability of Camellia chrysantha flower extract on Q235 steel in 1 M HCl was investigated using electrochemical impedance spectroscopy, polarization curve and weight loss method. This study was conducted to assess the efficacy of adding corrosion inhibitor to prevent Q235 steel from being corroded by the acid cleaning solution. FTIR spectrum showed that the extract of Camellia chrysantha contained carboxyl, hydroxyl, benzene, aromatic heterocyclic, double bond and other functional groups. As the temperature of the environment increases, the inhibition efficiency of corrosion inhibitors in pickling solutions decreases, while the concentration of the inhibitor has the opposite effect. The polarization curve indicated that the inhibitor was a mixed inhibitor. Impurity ions (Fe3+) have obvious influence on corrosion inhibition performance. Fe3+ reduces corrosion inhibition. When Fe3+ concentration is 500 mg/L, the inhibition efficiency is 65.13%.

The Relationship Between Bilingualism and Control Aspect of Intelligence: A Study of Persian-speaking Individuals.

The study of the relationship between bilingualism and the possible impact it might have on the control aspect of intelligence of adults in general and preschool children, in particular, has always been the subject of controversy for researchers. This research, following the related findings and gaps in the literature and inspired by Craik and Bialystok's (2005) framework, tries to divulge whether bilingualism could be related to the control aspect of intelligence. As our secondary goal, we also tried to see whether there are correlations between different tests assessing control. In this descriptive correlational study, via the convenience sampling method, we selected our participants. Methods: In doing so, 10 age-gender-matched Mazandarani-speaking monolinguals and the same matched bilinguals have been selected. Moreover, the literacy and socioeconomic status of subjects have been controlled. The tests for assessing subjects' executive control included day-night Stroop, the dimensional change card sort (DCCS), test of variables of attention (TOVA), and the computerized attention network test (ANT). Our participants' performance in language proficiency task as well as control tasks was demonstrated. Furthermore, via the conduction of the Pearson correlation statistics, the relationships between the participants' performance in diverse control tasks and language task were investigated. The results showed that bilinguals outperform monolinguals in all control tests except DCCS. Bilingualism could provide children with an executive control advantage promoting them in tasks demanding thought and action control. Language proficiency is not necessarily related to an advanced attentional control.Mazandarani-speaking monolinguals and bilinguals perform equally in the "knowledge" domain of intelligence.Bilinguals' performance in the control task of intelligence was better than their monolingual counterparts.It was corroborated that intelligence is not a homogeneous psychological construct.Generally, in tasks requiring suppression, bilinguals outperform monolinguals. The investigation of the relationship between control aspect of intelligence and the statue of monolingualism or bilingualism has always been the subject of controversy. "Control" aspect signifies the ability of an individual to suppress the provoking stimuli, that is, to ignore the external stimuli in favor of an intended linguistic or non-linguistic element. Our major objective in this research was to compare the performance of Mazandarani-speaking bilinguals and monolinguals in diverse control as well as vocabulary assessment tasks. Specifically, we wanted to see whether bilingual children could perform better than monolingual children in tasks requiring the inhibition capability. Furthermore, we attempted to investigate whether there were correlations between different control assessment tasks. Extending previous researches, we administered two additional cognitive tasks, namely, test of variables of attention (TOVA) and day and night task to evaluate our participants' control capability. In linguistic (vocabulary) proficiency assessment task, Peabody picture vocabulary task (PPVT), we did not find bilinguals' advantage over monolinguals. In contrast, bilinguals outperformed their monolingual counterparts in all other control tasks except dimensional change card sort (DCCS). Meanwhile, strong correlations between most control tasks were observed. The results corroborated that bilingual children outperformed their monolingual counterparts in tasks demanding strong thought and action control. Also, the conduction of most control tasks might be more challenging for monolinguals, and bilingual children, thanks to their linguistic statutes, could ignore irrelevant response or stimuli more easily, and perform better in the majority of cognitive control demanding tasks.

Neurotherapeutic Effects of Quercetin and Its Metabolite Compounds on Cognitive Impairment and Parkinson's Disease: An In Silico Study.

Little is known about the metabolomic profile of quercetin and its biological effects. This study aimed to determine the biological activities of quercetin and its metabolite products, as well as the molecular mechanisms of quercetin in cognitive impairment (CI) and Parkinson's disease (PD). Key methods used were MetaTox, PASS Online, ADMETlab 2.0, SwissADME, CTD MicroRNA MIENTURNE, AutoDock, and Cytoscape. A total of 28 quercetin metabolite compounds were identified by phase I reactions (hydroxylation and hydrogenation reactions) and phase II reactions (methylation, O-glucuronidation, and O-sulfation reactions). Quercetin and its metabolites were found to inhibit cytochrome P450 (CYP) 1A, CYP1A1, and CYP1A2. The studied compounds demonstrated significant gastrointestinal absorption and satisfied Lipinsky's criterion. Due to their high blood-brain barrier permeability, P-glycoprotein inhibition, anticancer, anti-inflammatory, and antioxidant capabilities, quercetin and its metabolite products have been proposed as promising molecular targets for the therapy of CI and PD. By regulating the expression of crucial signaling pathways [mitogen-activated protein kinase (MAPK) signaling pathway, and neuroinflammation and glutamatergic signaling], genes [brain derived neurotrophic factor (BDNF), human insulin gene (INS), and dopamine receptor D2 (DRD2), miRNAs (hsa-miR-16-5p, hsa-miR-26b-5p, hsa-miR-30a-5p, hsa-miR-125b-5p, hsa-miR-203a-3p, and hsa-miR-335-5p], and transcription factors [specificity protein 1 (SP1), v-rel avian reticuloendotheliosis viral oncogene homolog A (RELA), and nuclear factor Kappa B subunit 1 (NFKB1)], quercetin exhibited its neurotherapeutic effects in CI and PD. In addition to inhibiting β-N-acetylhexosaminidase, quercetin also showed robust interactions and binding affinities with heme oxygenase 1 (HMOX1), superoxide dismutase 2 (SOD2), tumor necrosis factor (TNF), nitric oxide synthase 2 (NOS2), brain-derived neurotrophic factor (BDNF), INS, DRD2, and γ-aminobutyric acid type A (GABAa). This study identified 28 quercetin metabolite products. The metabolites have similar characteristics to quercetin such as physicochemical properties, absorption, distribution, metabolism, and excretion (ADME), and biological activities. More research, especially clinical trials, is needed to find out how quercetin and its metabolites protect against CI and PD.

Design and screening of tetracycline antibiotics: an in-silico approach

A prominent class of broad-spectrum antibiotics known as tetracycline works by inhibiting the synthesis of proteins, which prevents the development of bacteria. Tetracycline resistance is typically attributed to one or more of the following causes: ribosomal binding site mutations, acquisition of mobile genetic elements carrying tetracycline-specific resistance genes, and/or chromosomal mutations that increase the expression of intrinsic resistance mechanisms. In this research, our objective is to virtually plan and conduct in-silico experiments to find tetracycline derivatives with inhibitory capability against tetracycline resistance protein. The tetracycline derivatives were screened using the Data Warrior, Discovery Studio, PyRx, and Swiss ADME web tools. Initially, 19 tetracycline derivatives were primarily screened for ADME and toxicity study followed by docking study. Among the tetracycline derivatives, C1, C11, C12, C14, C16, and C17 were found to be the potential drug-like molecules with binding energies of -8.9 kcal/mol, -8.4 kcal/mol, -8.5 kcal/mol, -7.7 kcal/mol, -7.7 kcal/mol, -8.6 kcal/mol respectively. In particular, C1 was predicted to have a better binding affinity towards the target protein than the others.

Laser-activatable oxygen self-supplying nanoplatform for efficiently overcoming colorectal cancer resistance by enhanced ferroptosis and alleviated hypoxic microenvironment

BackgroundColorectal cancer (CRC) is the second most deadly cancer worldwide, with chemo-resistance remaining a major obstacle in CRC treatment. Notably, the imbalance of redox homeostasis-mediated ferroptosis and the modulation of hypoxic tumor microenvironment are regarded as new entry points for overcoming the chemo-resistance of CRC.MethodsInspired by this, we rationally designed a light-activatable oxygen self-supplying chemo-photothermal nanoplatform by co-assembling cisplatin (CDDP) and linoleic acid (LA)-tailored IR820 via enhanced ferroptosis against colorectal cancer chemo-resistance. In this nanoplatform, CDDP can produce hydrogen peroxide in CRC cells through a series of enzymatic reactions and subsequently release oxygen under laser-triggered photothermal to alleviate hypoxia. Additionally, the introduced LA can add exogenous unsaturated fatty acids into CRC cells, triggering ferroptosis via oxidative stress-related peroxidized lipid accumulation. Meanwhile, photothermal can efficiently boost the rate of enzymatic response and local blood flow, hence increasing the oxygen supply and oxidizing LA for enhanced ferroptosis.ResultsThis nanoplatform exhibited excellent anti-tumor efficacy in chemo-resistant cell lines and showed potent inhibitory capability in nude mice xenograft models.ConclusionsTaken together, this nanoplatform provides a promising paradigm via enhanced ferroptosis and alleviated hypoxia tumor microenvironment against CRC chemo-resistance.Graphical

Novel Water-Based Mud for Low-Permeable Reservoir in South China Sea

Conventional reservoir drill-in fluids used for drilling reservoirs in Weizhou Oilfield encounter rheological problems that result in technical problems such as hole-cleaning in openhole horizontal intervals. Hence, novel drill-in fluid was developed by optimizing the additive quantity and particle size distribution. Lab tests showed that novel drill-in fluids boast high low shearing rate viscosity, and provide promising cutting, carrying, and suspension capabilities. Furthermore, the novel drill-in fluids performed well in reservoir protection, with a permeability recovery rate of more than 90%. The novel drill-in fluids also have high inhibition capabilities with a linear expansion rate of mud shale as low as 10%, with a rolling recovery rate of up to 96.48%. Field application results showed no pipe-stuck was encountered during tripping in the horizontal interval when using the novel drill-in fluid. Moreover, by using the novel drill-in fluids, skin factor was reduced from 20.0 to −3.0, and daily oil production was double what was expected. It was concluded that novel drill-in fluids meets the demand of horizontal drilling intervals in Weizhou Oilfield and improves hole-cleaning and reservoir protection in the horizontal well.

Epigallocatechin gallate-derived carbonized polymer dots: A multifunctional scavenger targeting Alzheimer's β-amyloid plaques.

The design of high-efficiency scavengers targeting β-amyloid protein (Aβ) plaques in the progress of Alzheimer's disease (AD) has been recognized as an effective way to prevent and treat AD. Herein, epigallocatechin gallate (EGCG)-derived carbonized polymer dots (E-CPDs) were synthesized for the first time via a hydrothermal method using EGCG, an Aβ inhibitor, as one of the raw materials. The inhibitory efficiency and fluorescent property of E-CPDs were elegantly modulated by adjusting the molar ratio of EGCG to nitrogen-containing dopant, o-phenylenediamine (oPD), and 75E-CPDs fabricated with 75 mM EGCG and 50 mM oPD showed the highest inhibitory capability. The multifunctionality of 75E-CPDs on inhibition of Aβ fibrillization, Aβ fibrils disaggregation, amyloid fluorescent detection, and intracellular reactive oxygen species scavenging was demonstrated. 75E-CPDs inhibited the formation of β-sheet-rich Aβ aggregates, alleviated Aβ-induced cytotoxicity of cultured cells from 47% to 15%, and prolonged the lifespan of AD nematodes by scavenging in vivo amyloid plaques, demonstrating much higher performance than either EGCG or EGCG-free carbon dots. Notably, 75E-CPDs could rapidly disaggregate Aβ fibrils on "second" scale, faster than any other disaggregating agents. The aromatic structure as well as hydroxyl and carboxyl groups existing on 75E-CPDs surface, which would interact with Aβ species via hydrogen bonding, electrostatic interactions, and hydrophobic interactions, played critical roles in their inhibition and disaggregation capabilities. This work reveals that potent CDs can be fabricated by using an Aβ inhibitor as the precursor, providing a new perspective for the design of multifunctional scavengers targeting amyloid plaques. STATEMENT OF SIGNIFICANCE: Alzheimer's disease (AD) is one of the top ten causes of death worldwide and seriously threatens human health. Recently, carbon nanomaterials have attracted much attention because of their good biocompatibility and capability in modulating Aβ aggregation via multiple interactions. This work has for the first time fabricated epigallocatechin gallate-derived carbonized polymer dots (E-CPDs) and revealed the multifunctional potency of E-CPDs on alleviating the multifaced symptoms associated with β-amyloid protein (Aβ) fibrillization in the progression of AD. Notably, E-CPDs exhibited enhanced fluorescence emission upon binding to Aβ fibrils, possessing potential as Aβ fluorescent probes. It is believed that this work would open a new horizon in the design of multifunctional carbon nanomaterials as a potent amyloid scavenger for AD theranostics.

Smart Chondroitin Sulfate Micelles for Effective Targeted Delivery of Doxorubicin Against Breast Cancer Metastasis.

Metastasis is a major challenge in breast cancer therapy. The successful chemotherapy of breast cancer largely depends on the ability to block the metastatic process. Herein, we designed a dual-targeting and stimuli-responsive drug delivery system for targeted drug delivery against breast cancer metastasis. AS1411 aptamer-modified chondroitin sulfate A-ss-deoxycholic acid (ACSSD) was synthesized, and the unmodified CSSD was used as the control. Chemotherapeutic drug doxorubicin (DOX)-containing ACSSD (D-ACSSD) micelles were prepared by a dialysis method. The ACSSD conjugate was confirmed by Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), dynamic light scattering (DLS), and transmission electron microscopy (TEM). In vitro cellular uptake and cytotoxicity of D-ACSSD micelles were studied by confocal laser scanning microscopy (CLSM) and MTT assay in breast tumor cells. The inhibition capability of D-ACSSD micelles in cell migration and invasion was carried out in 4T1 cells. In vivo antitumor activity of DOX-containing micelles was investigated in metastatic 4T1-bearing Balb/c mice. D-ACSSD and DOX-loaded CSSD (D-CSSD) micelles exhibited high drug encapsulation content and reduction-responsive characteristics. D-ACSSD micelles were spherical in shape. Compared with D-CSSD, D-ACSSD showed higher cellular uptake and more potent killing activity in 4T1 and MDA-MB-231 cells. Additionally, D-ACSSD exhibited stronger inhibitory effects on the invasion and migration of highly metastatic 4T1 cells than unmodified D-CSSD. Among the DOX-containing formulations, D-ACSSD micelles presented the most effective inhibition of tumor growth and lung metastasis in orthotopic 4T1-bearing mice in vivo. It also revealed that ACSSD micelles did not exhibit obvious systemic toxicity. The smart D-ACSSD micelles could be a promising delivery system for the therapy of metastatic breast cancer.

Profiling of phytochemicals using LC-ESI-MS2 , in vitro, in vivo characterization and cosmeceutical effects of Alpinia galanga (wild) extract loaded emulgel.

The potential as a depigmenting agent, sun protection, and healthy benefits is indicated by the sun protection factor, radical scavenging, and tyrosinase inhibitory activities of Alpinia galanga (wild). A stable emulgel containing A .galanga (wild) extract is prepared. This emulgel is then characterized by in vitro evaluation and identification of contents by LC-ESI-MS2 . In vivo performance is counted in terms of moisturizing, melanin level, erythema, sebum, skin fine pores and large pores analysis, and other related physiological skin parameters. DPPH radical scavenging activity, total phenolic and flavonoid counts were used to measure the free radical scavenging and tyrosinase inhibitory capability of A .galanga (wild) extract, respectively. LC-ESI-MS2 used for phytochemical analysis. Emulgels synthesize, and their globule size, Ultracentrifugation, pH, and conductivity were all evaluated. Among the developed formulations, the optimal emulgels formulation underwent 90-day stability tests for organoleptic characteristics and rheology at 8°C, 25°C, 40°C, and 40°C + 75% RH (relative humidity). Using sebumeter®, mexameter®, and corneometer®, changes in skin physiological parameters were assessed over the course of 12 weeks in 13 healthy male, Asian volunteers. VisioFace® is used for computational analysis of high-resolution pictures to determine the % area, fine pore counts, and large pore counts of the skin. The antioxidant, tyrosinase inhibitory potential and counts of total phenolic and flavonoids of A .galanga (wild) extract were impressive (85%, 75%, and 48.0mg GAE/g and 14.37 mg quercetin/g, respectively). In terms of stability evaluation, globule size (0.7528 ± 0.192μm). Optimized A .galanga (wild) ethanol aqueous (AGEA) extract loaded emulgel was stable in terms of organoleptic and in vitro evaluation. The AGEA formulation significantly reduced the amount of sebum, erythema, fine pore counts, large pore counts, fine pore % area and large pores area percentage while significantly improved the moisture and elasticity of the skin. A stable A .galanga (wild) extract loaded emulgel was successfully produced that improved the skin physiological parameters in terms of skin's sebum, erythema, moisturizing, melanin, and pores.

Nanoseeded Desupersaturation and Dissolution Tests for Elucidating Supersaturation Maintenance in Amorphous Solid Dispersions.

The impact of residual drug crystals that are formed during the production and storage of amorphous solid dispersions (ASDs) has been studied using micron-sized seed crystals in solvent-shift (desupersaturation) and dissolution tests. This study examines the impacts of the seed size loading on the solution-mediated precipitation from griseofulvin ASDs. Nanoparticle crystals (nanoseeds) were used as a more realistic surrogate for residual crystals compared with conventional micron-sized seeds. ASDs of griseofulvin with Soluplus (Sol), Kollidon VA64 (VA64), and hydroxypropyl methyl cellulose (HPMC) were prepared by spray-drying. Nanoseeds produced by wet media milling were used in the dissolution and desupersaturation experiments. DLS, SEM, XRPD, and DSC were used for characterization. The results from the solvent-shift tests suggest that the drug nanoseeds led to a faster and higher extent of desupersaturation than the as-received micron-sized crystals and that the higher seed loading facilitated desupersaturation. Sol was the only effective nucleation inhibitor; the overall precipitation inhibition capability was ranked: Sol > HPMC > VA64. In the dissolution tests, only the Sol-based ASDs generated significant supersaturation, which decreased upon an increase in the nanoseed loading. This study has demonstrated the importance of using drug nanocrystals in lieu of conventional coarse crystals in desupersaturation and dissolution tests in ASD development.

Isolation and characterization of lactic acid bacteria with potential probiotic activity and further investigation of their activity by α-amylase and α-glucosidase inhibitions of fermented batters.

Probiotic microbiota plays a vital role in gastrointestinal health and possesses other beneficial attributes such as antimicrobial and antibiotic agents along with a significant role in the management of diabetes. The present study identifies the probiotic potential of Lactobacillus spp. isolated from three traditionally fermented foods namely, jalebi, medhu vada, and kallappam batters at biochemical, physiological, and molecular levels. By 16S rRNA gene amplification and sequencing, the isolates were identified. A similarity of >98% to Lacticaseibacillus rhamnosus RAMULAB13, Lactiplantibacillus plantarum RAMULAB14, Lactiplantibacillus pentosus RAMULAB15, Lacticaseibacillus paracasei RAMULAB16, Lacticaseibacillus casei RAMULAB17, Lacticaseibacillus casei RAMULAB20, and Lacticaseibacillus paracasei RAMULAB21 was suggested when searched for homology using NCBI database. Utilizing the cell-free supernatant (CS), intact cells (IC), and cell-free extract (CE) of the isolates, inhibitory potential activity against the carbohydrate hydrolyzing enzymes α-glucosidase and α-amylase was assessed. CS, CE, and IC of the isolates had a varying capability of inhibition against α-glucosidase (15.08 to 59.55%) and α-amylase (18.79 to 63.42%) enzymes. To assess the probiotic potential of seven isolates, various preliminary characteristics were examined. All the isolates exhibited substantial tolerance toward gastrointestinal conditions and also demonstrated the highest survival rate (> 99%), hydrophobicity (> 65%), aggregation (> 76%), adherence to HT-29 cells (> 84%), and chicken crop epithelial cells suggesting that the isolates had a high probiotic attribute. Additionally, the strains showed remarkable results in safety assessment assays (DNase and hemolytic), and antibacterial and antibiotic evaluations. The study concludes that the lactic acid bacteria (LAB) characterized possesses outstanding probiotic properties and has antidiabetic effects. In order to obtain various health advantages, LAB can be utilized as probiotic supplements.

Raspberry Ketone-Mediated Inhibition of Biofilm Formation in Salmonella enterica Typhimurium-An Assessment of the Mechanisms of Action.

Salmonella enterica is an important foodborne pathogen that causes gastroenteritis and systemic infection in humans and livestock. Salmonella biofilms consist of two major components-amyloid curli and cellulose-which contribute to the prolonged persistence of Salmonella inside the host. Effective agents for inhibiting the formation of biofilms are urgently needed. We investigated the antibiofilm effect of Raspberry Ketone (RK) and its mechanism of action against Salmonella Typhimurium 14028 using the Congo red agar method, Calcofluor staining, crystal violet method, pellicle assay, and the TMT-labeled quantitative proteomic approach. RK suppressed the formation of different types of Salmonella biofilms, including pellicle formation, even at low concentrations (200 µg/mL). Furthermore, at higher concentrations (2 mg/mL), RK exhibited bacteriostatic effects. RK repressed cellulose deposition in Salmonella biofilm through an unknown mechanism. Swimming and swarming motility analyses demonstrated reduced motility in RK-treated S. typhimurium. Proteomics analysis revealed that pathways involved in amyloid curli production, bacterial invasion, flagellar motility, arginine biosynthesis, and carbohydrate metabolism, were targeted by RK to facilitate biofilm inhibition. Consistent with the proteomics data, the expressions of csgB and csgD genes were strongly down-regulated in RK-treated S. typhimurium. These findings clearly demonstrated the Salmonella biofilm inhibition capability of RK, justifying its further study for its efficacy assessment in clinical and industrial settings.

Chemical Modification of Auranofin Yields a New Family of Anticancer Drug Candidates: The Gold(I) Phosphite Analogues.

A panel of four novel gold(I) complexes, inspired by the clinically established gold drug auranofin (1-Thio-β-D-glucopyranosatotriethylphosphine gold-2,3,4,6-tetraacetate), was prepared and characterized. All these compounds feature the replacement of the triethylphosphine ligand of the parent compound auranofin with a trimethylphosphite ligand. The linear coordination around the gold(I) center is completed by Cl-, Br-, I- or by the thioglucose tetraacetate ligand (SAtg). The in-solution behavior of these gold compounds as well as their interactions with some representative model proteins were comparatively analyzed through 31PNMR and ESI-MS measurements. Notably, all panel compounds turned out to be stable in aqueous media, but significant differences with respect to auranofin were disclosed in their interactions with a few leading proteins. In addition, the cytotoxic effects produced by the panel compounds toward A2780, A2780R and SKOV-3 ovarian cancer cells were quantitated and found to be in the low micromolar range, since the IC50 of all compounds was found to be between 1 μM and 10 μM. Notably, these novel gold complexes showed large and similar inhibition capabilities towards the key enzyme thioredoxin reductase, again comparable to those of auranofin. The implications of these results for the discovery of new and effective gold-based anticancer agents are discussed.

HMG – CoA reductase inhibition mediated hypocholesterolemic potential of myricetin and quercetin: in-silico and in-vivo studies

ABSTRACT The study was aimed to examine the HMG-CoA reductase (HMGCR) inhibition potential. The in-silico investigations followed the assessments of molecular docking, druggability and molecular dynamics. The molecular dynamics was performed at 100 ns by calculating interaction free energies, RSMD, RSMF, radius of gyration and SASA. Consequently, in-vivo examinations were performed by using a hypercholesterolemic rabbit animal model. The molecular docking showed significant interaction capabilities of myricetin as revealed by binding energy data up to −8.4 Kcal/mol. Accordingly, the data of molecular dynamics i.e. free energy, solvation free energy, radius of gyration, RSMD, RSMF and SASA were shown significant interaction capabilities of myricetin with HMGCR. Supportively, significant ameliorations were made in lipid profile, dyslipidemia indices and oxidative stress by the treatments of myricetin compared to quercetin and atorvastatin. Thus, it can be concluded that myricetin is a potent flavanol with significant potential for HMGCR inhibition and free radical scavenging capability.

Abstract B033: Determining the tumor supportive and inhibitory capabilities of cancer associated fibroblast subpopulations in central nervous system metastasis. [R

Abstract Central nervous metastases (CM), like all tumors, are surrounded by a complex tumor microenvironment (TME) comprised of a meshwork of extracellular matrix (ECM) proteins and an assemblage of cell types including endothelial cells, pericytes, immune cells, and cancer-associated fibroblasts (CAFs). We have previously shown that CAFs can either support or inhibit tumor growth, suggesting that CM CAFs comprise a heterogenous subgroup of cells. Recently we reported, based on literature in other cancer types, that CAFs can be categorized into four main subpopulations: ‘desmoplastic’, ‘immune’, ‘contractile’ and ‘aggressive’. Accordingly, the purpose of our study is to identify CAF subpopulations in the TME of CM and determine their impact on CM growth. In order to identify CM CAF subpopulations and their respective markers, we performed single cell RNA sequencing (scRNA-seq) on 7 CM patient tissues and 4 patient-derived CM CAF cell lines established in our lab. We then used fluorescence-activated cell sorting (FACS) to enrich different CAF subpopulations in CAF cell lines for further molecular and functional in vitro and in vivo characterization. ScRNA-seq data in 7 CM tissues revealed the presence of CAFs. Upon further analysis, we identified the desmoplastic, immune, contractile, and aggressive CAF subpopulations. In the CAF cell lines, we identified the desmoplastic and aggressive CAF subpopulations. We propose that desmoplastic CAFs are tumor inhibitory and aggressive CAFs are tumor supporting. The desmoplastic subpopulation is characterized by high expression of Immunoglobulin Superfamily Containing Leucine Rich Repeat (ISLR) and low expression of a classic tumor supportive CAF marker Actin Alpha 2, Smooth Muscle (ACTA2, a-SMA). ISLR has recently been reported to be overexpressed in CAFs with tumor inhibitory capabilities in other cancer types. The aggressive subpopulation shows low ISLR expression and high a-SMA expression. FACS on one of the patient-derived CM CAF cell lines using ISLR antibody enriched ISLRhigh CAFs, with remaining CAFs confirmed to be ISLRlow. Further western blotting analysis revealed lower expression of a-SMA in ISLRhigh cells as compared to ISLRlow cells. This reciprocal expression of ISLR and a-SMA could represent the molecular basis driving the phenotype of desmoplastic and aggressive CAF subpopulations. Further in vitro and in vivo experiments are currently underway in our lab to determine the necessity and sufficiency of ISLR and a-SMA in determining tumor supportive capabilities of both desmoplastic and aggressive CAFs. The present study improves our understanding of the CM TME, which ultimately will help establish new strategies to harness the cancer restraining capabilities of tumor inhibitory CAFs in clinic to improve outcomes for patients with CM. Citation Format: Thomas Simon, David N. Buckley, Gerald C. Gooden, Ben Y. Tew, Gabriel Zada, Bodour Salhia. Determining the tumor supportive and inhibitory capabilities of cancer associated fibroblast subpopulations in central nervous system metastasis. [R [abstract]. In: Proceedings of the AACR Special Conference: Cancer Metastasis; 2022 Nov 14-17; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_2):Abstract nr B033.

Strong Convection-Dependent Adsorption of Phenothiazine Skeleton Levelers and Their Application in Copper Electroplating

The design and synthesis of high-performance levelers remain a major challenge to date. Herein, a series of phenothiazine (PTZ) derivatives were designed and synthesized, and they had a butterfly conformation, and their adsorption capacities were easier to modulate. To check out the inhibition capabilities among these eight PTZ derivatives, electrochemical measurements and theoretical calculations were carried out, and PTZ-8 indicated the strongest inhibition capabilities among these PTZ derivatives. Besides, galvanostatic measurements were also carried out to evaluate the overall performance of the levelers. The results showed that PTZ-8 had a potential oscillation, but PTZ-6 had strong convection-dependent adsorption. Due to the potential oscillation of PTZ-8, PTZ-6 as the representative leveler was selected for through-hole electrodeposition. In addition, field-emission scanning electron microscope images and X-ray diffraction results displayed the surface morphology, which indicated that the addition of PTZ-6 could lead to a fine copper deposit and cause the preferential orientations of copper deposits to change from [220] to [111]. This study might lay the foundation for the design of high-performance levelers.

Polysulfone Membranes Doped with Human Neutrophil Elastase Inhibitors: Assessment of Bioactivity and Biocompatibility.

The use of polysulfone (PSU) hemodialysis (HD) membranes modified with bioactive compounds has gained relevance in chronic kidney disease (CKD) management. Compounds based on the 4-oxo-β-lactam scaffold have outstanding inhibitory ability and selectivity for human neutrophil elastase (HNE). The present work aimed to evaluate the bioactivity and biocompatibility of PSU-based HD membranes doped with HNE inhibitors (HNEIs). For this, two 4-oxo-β-lactam derivates (D4L-1 and D4L-2) synthesized in house were used, as well as a commercial HNEI (Sivelestat), for comparison purposes. Their HNE inhibition efficacy was evaluated in in vitro and ex vivo (incubations with human plasma) assay conditions. All biomaterials were bioactive and hemocompatible. The inhibitory capacity of the HNEIs and HNEI-PSU membranes in vitro was D4L-1 > D4L-2 > Sivelestat and D4L-2 > Sivelestat > D4L-1, respectively. In ex vivo conditions, both HNEIs and HNEI-PSU materials presented the same relative inhibitory ability (D4L-1 > D4L-2 > Sivelestat). The difference observed between in vitro and ex vivo conditions is most likely due to the inherent lipophilicity/hydrophobicity of each HNEI influencing their affinity and accessibility to HNE when trapped in the membrane. Compared to Sivelestat, both D4L-1 and D4L-2 (and the respective doped membranes) have more potent inhibition capabilities. In conclusion, this work reports the successful development of PSU membranes functionalized with HNEIs.

Inhibitory Capabilities of Sweet Yellow Capsicum Extract toward the Rusting of Steel Rebars in Cement Pore Solution.

The inhibitory capabilities of the sweet yellow capsicum extract (SYCE) toward the rusting of steel rebars in cement pore solution (CPS) were tested employing the electrochemical and mass loss methods. Gallic acid, caffeic acid, p-coumaric acid, ferulic acid, luteolin, and cinnamic acid are the most important constituents in the SYCE extract. By adsorbing them on steel bars, the organic compounds in the CSA extract enable them with an effective mixed-type inhibition, suppressing both anodic and cathodic procedures. At 300 ppm, the highest performances were 95.3 and 97.5% utilizing mass loss and electrochemical approaches, respectively. The activation energy for the corrosion process is greatly increased by the addition of the SYCE extract, going from 13.2 kJ mol-1 (blank solution) to 30.0 kJ mol-1 (300 ppm SYCE extract). The physical adsorption actions of the SYCE extract are described by the Freundlich equilibrium constant's smallest value, which is 0.074 ppm-1. Many future investigators will be attracted by these discoveries to work relentlessly to uncover the anti-corrosion characteristics of novel plant extracts in the area of concrete additives.