Computational Analysis of Lenalidomide and Pomalidomide Enantiomers' Binding Interactions With Prostaglandin (PG)-Protein: Implications for Inflammatory Activity in Cancer.

BACKGROUND: Lenalidomide and Pomalidomide are chiral immunomodulatory drugs (IMiDs) and have antiangiogenic and anti-immunomodulatory activity. Each enantiomer may have distinct binding and biological activity. This study aimed to explore the in-silico binding of both enantiomers of Lenalidomide and Pomalidomide with Prostaglandin and its potential impact on persisting inflammatory activity in cancer. This can further provide insight into the transport of pro-inflammatory mediators and their potential implications for the inflammatory microenvironment within tumors. MATERIALS AND METHODS: Molecular docking studies were performed to explore the binding potential of both enantiomers of Lenalidomide and Pomalidomide with Pg protein. The crystal structure of Pg-protein (PDB ID: 1IW7) was obtained from the Protein Data Bank. RESULTS: The binding energies for (-)-Lenalidomide and (+)-Lenalidomide were -6.7 and -7.2 kcal/mol, respectively, while the binding energies for (-)-Pomalidomide and (+)-Pomalidomide were -7.8 and -8.1 kcal/mol, respectively. The binding mode analysis revealed that all four compounds formed hydrogen bonds with key amino acid residues of Pg-protein. The hydrogen bond distances for (-)-Lenalidomide, (+)-Lenalidomide, (-)-Pomalidomide, and (+)-Pomalidomide were 2.1 Å, 2.0 Å, 2.2 Å, and 2.1 Å, respectively. CONCLUSIONS: The present study suggests that both enantiomers of Lenalidomide and Pomalidomide have a high affinity for Pg-protein and can effectively target the Pg-protein pathway to persist inflammatory activity in cancer. By targeting inflammation-mediated processes, these drugs may offer a novel strategy to combat tumor progression.

Uncovering the diversity of pathogenic invaders: insights into protozoa, fungi, and worm infections.

Post COVID-19, there has been renewed interest in understanding the pathogens challenging the human health and evaluate our preparedness towards dealing with health challenges in future. In this endeavour, it is not only the bacteria and the viruses, but a greater community of pathogens. Such pathogenic microorganisms, include protozoa, fungi and worms, which establish a distinct variety of disease-causing agents with the capability to impact the host's well-being as well as the equity of ecosystem. This review summarises the peculiar characteristics and pathogenic mechanisms utilized by these disease-causing organisms. It features their role in causing infection in the concerned host and emphasizes the need for further research. Understanding the layers of pathogenesis encompassing the concerned infectious microbes will help expand targeted inferences with relation to the cause of the infection. This would strengthen and augment benefit to the host's health along with the maintenance of ecosystem network, exhibiting host-pathogen interaction cycle. This would be key to discover the layers underlying differential disease severities in response to similar/same pathogen infection.

Siderophore-mediated iron acquisition by Klebsiella pneumoniae.

Microbes synthesize and secrete siderophores, that bind and solubilize precipitated or otherwise unavailable iron in their microenvironments. Gram (-) bacterial TonB-dependent outer membrane receptors capture the resulting ferric siderophores to begin the uptake process. From their similarity to fepA, the structural gene for the Escherichia coli ferric enterobactin (FeEnt) receptor, we identified four homologous genes in the human and animal ESKAPE pathogen Klebsiella pneumoniae (strain Kp52.145). One locus encodes IroN (locus 0027 on plasmid pII), and three other loci encode other FepA orthologs/paralogs (chromosomal loci 1658, 2380, and 4984). Based on the crystal structure of E. coli FepA (1FEP), we modeled the tertiary structures of the K. pneumoniae FepA homologs and genetically engineered individual Cys substitutions in their predicted surface loops. We subjected bacteria expressing the Cys mutant proteins to modification with extrinsic fluorescein maleimide (FM) and used the resulting fluorescently labeled cells to spectroscopically monitor the binding and transport of catecholate ferric siderophores by the four different receptors. The FM-modified FepA homologs were nanosensors that defined the ferric catecholate uptake pathways in pathogenic strains of K. pneumoniae. In Kp52.145, loci 1658 and 4984 encoded receptors that primarily recognized and transported FeEnt; locus 0027 produced a receptor that principally bound and transported FeEnt and glucosylated FeEnt (FeGEnt); locus 2380 encoded a protein that bound ferric catecholate compounds but did not detectably transport them. The sensors also characterized the uptake of iron complexes, including FeGEnt, by the hypervirulent, hypermucoviscous K. pneumoniae strain hvKp1. IMPORTANCE: Both commensal and pathogenic bacteria produce small organic chelators, called siderophores, that avidly bind iron and increase its bioavailability. Klebsiella pneumoniae variably produces four siderophores that antagonize host iron sequestration: enterobactin, glucosylated enterobactin (also termed salmochelin), aerobactin, and yersiniabactin, which promote colonization of different host tissues. Abundant evidence links bacterial iron acquisition to virulence and infectious diseases. The data we report explain the recognition and transport of ferric catecholates and other siderophores, which are crucial to iron acquisition by K. pneumoniae.

Specificity and mechanism of TonB-dependent ferric catecholate uptake by Fiu.

We studied the Escherichia coli outer membrane protein Fiu, a presumed transporter of monomeric ferric catecholates, by introducing Cys residues in its surface loops and modifying them with fluorescein maleimide (FM). Fiu-FM bound iron complexes of the tricatecholate siderophore enterobactin (FeEnt) and glucosylated enterobactin (FeGEnt), their dicatecholate degradation product Fe(DHBS)2 (FeEnt*), the monocatecholates dihydroxybenzoic acid (FeDHBA) and dihydroxybenzoyl serine (FeDHBS), and the siderophore antibiotics cefiderocol (FDC) and MB-1. Unlike high-affinity ligand-gated porins (LGPs), Fiu-FM had only micromolar affinity for iron complexes. Its apparent KD values for FeDHBS, FeDHBA, FeEnt*, FeEnt, FeGEnt, FeFDC, and FeMB-1 were 0.1, 0.7, 0.7, 1.0, 0.3, 0.4, and 4 µM, respectively. Despite its broad binding abilities, the transport repertoires of E. coli Fiu, as well as those of Cir and FepA, were less broad. Fiu only transported FeEnt*. Cir transported FeEnt* and FeDHBS (weakly); FepA transported FeEnt, FeEnt*, and FeDHBA. Both Cir and FepA bound FeGEnt, albeit with lower affinity. Related transporters of Acinetobacter baumannii (PiuA, PirA, BauA) had similarly moderate affinity and broad specificity for di- or monomeric ferric catecholates. Both microbiological and radioisotopic experiments showed Fiu's exclusive transport of FeEnt*, rather than ferric monocatecholate compounds. Molecular docking and molecular dynamics simulations predicted three binding sites for FeEnt*in the external vestibule of Fiu, and a fourth site deeper in its interior. Alanine scanning mutagenesis in the outermost sites (1a, 1b, and 2) decreased FeEnt* binding affinity as much as 20-fold and reduced or eliminated FeEnt* uptake. Finally, the molecular dynamics simulations suggested a pathway of FeEnt* movement through Fiu that may generally describe the process of metal transport by TonB-dependent receptors.

CB-0821, a novel CC chemokine receptor 5 (CCR5) inhibitor with improved binding efficacy proposed as anti-HIV candidate: Computational and in vitro approach.

The CC chemokine receptor 5 (CCR5) serves a pivotal role in human immunodeficiency virus 1 (HIV-1) infection by acting as a co-receptor and facilitating the binding of the viral envelope glycoprotein (env). Maraviroc (MVC), a Food and Drug Administration-approved monocarboxylic acid amide, is one of the CCR5 inhibitors employed in HIV treatment. Despite the existence of approved drugs, the emergence of drug resistance underscores the necessity for novel compounds to combat resistance and enhance therapeutic efficacy. In this study, CB-0821, identified from the ChemBridge library, emerged as a promising CCR5 inhibitor. Molecular dynamics simulations indicate comparable dynamic properties for CB-0821 and MVC. In silico comparisons with other CCR5 inhibitors emphasize CB-0821's superior binding affinity, positioning it as a potential lead compound. Evaluations of the dissociation constant (Ki) and absorption, distribution, metabolism, and excretion predictions suggest CB-0821 as a well-tolerated drug. Furthermore, the dose-dependent inhibition of CCR5 by CB-0821 in Peripheral blood mononuclear cells (PBMCs) (ranging from 10 to 200 nM) demonstrates efficacy, coupled with nontoxicity to Vero cells at concentrations up to 500 nM. These results underscore the potential of CB-0821 in HIV antiviral therapy, calling for additional preclinical validations before advancing to clinical considerations.

Downregulation of protein phosphatase 2Aα in asthmatic airway smooth muscle.

Airway smooth muscle cell (ASM) is renowned for its involvement in airway hyperresponsiveness through impaired ASM relaxation and bronchoconstriction in asthma which poses a significant challenge in the field. Recent studies have explored different targets in ASM to alleviate airway hyperresponsiveness, however, a sizeable portion of asthmatics still experience poor control. In our study, we explored protein phosphatase 2A (PP2A) in ASM as it has been reported to regulate cellular contractility by controlling intracellular calcium ([Ca2+]i), ion channels, and respective regulatory proteins. We obtained human ASM cells and lung tissues from healthy and asthmatic patients and evaluated PP2A expression using RNA Seq data, immunofluorescence, and immunoblotting. We further investigated the functional importance of PP2A by determining its role in bronchoconstriction using mouse bronchus and human ASM [Ca2+]i regulation. We found ubiquitous expression of PP2A isoforms in human ASM with PP2Aα being predominantly expressed. Interestingly, PP2Aα was significantly downregulated in asthmatic tissue and human ASM exposed to pro-inflammatory cytokines. Functionally, PP2Aα activation inhibited acetylcholine or methacholine induced bronchial contraction in mouse bronchus and further potentiated isoproterenol-induced bronchial relaxation. Mechanistically, PP2Aα activation inhibited histamine evoked [Ca2+]i response and myosin light chain (MLC) phosphorylation in the presence of interleukin-13 (IL-13) in human ASM cells. To conclude, we for the first time established the PP2A signaling in ASM which can be further explored to develop novel therapeutics to alleviate airway hyperresponsiveness in asthma.

Influence of the Curve of Spee on Tooth Displacement Patterns: A Finite Element Analysis at Varying Implant Heights.

Background Monocortical mini-screw-type temporary anchorage devices (TADs), or mini-screws, have significantly impacted orthodontic treatment strategies, especially in severe crowding and protrusion cases. These devices offer flexibility in placement sites, but the chosen location can considerably influence tooth displacement patterns. Key factors include the 'line of force' and the biomechanical properties of orthodontic tools. By analyzing tension distribution and three-dimensional displacements, the finite element method (FEM) provides a thorough means to comprehend these patterns. The Curve of Spee (COS) is a crucial factor potentially affecting displacement. Objective This study aimed to leverage finite element analysis (FEA) to understand the impact of varying mini-implant heights (10 mm, 13 mm, and 16 mm) on the displacements of different tooth types under a consistent force of 150 gm and compare these displacements both in the presence and absence of the COS. Materials and methods A CAD model of the jaw and teeth was developed using CT scan data and a Rexcan III 3D White Light Scanner. This model was meshed in Altair HyperMesh using tetrahedral elements, resulting in a Finite Element Model. The model incorporated various components, including teeth, the periodontal ligament (PDL), alveolar bone, brackets, a titanium mini-screw, and an archwire measuring 0.019 x 0.025 inches. Unique material properties were assigned to the PDL, and the assembly accurately replicated the clinical alignment of the archwire and brackets. Subsequently, stress and strain analyses were conducted on the model using the FEM. Results The displacement patterns of various teeth at implant heights of 10 mm, 13 mm, and 16 mm under a 150-gm force were analyzed in relation to the COS. Notably, for the central incisor, the COS significantly affected displacements in the Y and Z directions. Similarly, the Lateral Incisor and Canine exhibited marked changes in the Z direction with the presence of the COS. The Second Premolar's apex displacement showed significant variation due to the COS, while the First Molar displayed notable changes in the X direction. Generally, the presence of the COS either maintained or slightly increased Z-directional displacements across teeth, particularly at the apices. Conclusion The presence of COS significantly influences tooth displacement patterns when using mini-screws at different implant heights. Central incisors, lateral incisors, and canines are particularly sensitive to changes in the Z direction with the COS. The biomechanical analysis emphasizes the importance of considering COS in treatment planning for optimal results with mini-implants in orthodontics.

Functional Outcomes and Gait Analysis of Total Hip Arthroplasty Through Lateral Hardinge Approach and Gluteus Medius-Sparing Approach: A Prospective Study.

Background and objective Hip degenerative joint disease is a common and debilitating musculoskeletal disorder. Total hip arthroplasty (THA) is a reconstructive hip procedure to relieve this condition through various surgical approaches. This study aimed to compare the functional outcomes between patients undergoing THA using the lateral Hardinge approach and the lateral gluteus medius-sparing approach. Material and methods This prospective study was carried out at a tertiary care institution. Thirty patients with arthritic hip joints were managed with total hip replacement (THR). The patients were allocated into two treatment groups; in group A, 14 patients received a THR by the lateral Hardinge approach, whereas in group B, 16 patients were managed by the lateral gluteus medius-sparing approach. Functional outcomes were assessed by the Harris Hip Score (HHS), and gait analysis was performed. Results The mean age of group A was 39.79 ±14.01 years and that of group B was 37.00 ±14.81 years. The mean length of incision was significantly lower in group B (p=0.001), whereas the mean duration of surgery (p=0.018) and mean contralateral pelvic tilt were found to be significantly lower in group A (p=0.009). No significant difference was found in abductor muscle strength, limb length discrepancy, HHS, pelvic obliquity, and pelvic rotation. Conclusion While functional outcomes were similar in both groups, the group that underwent THA with the gluteus medius-sparing approach had better gait based on lower pelvic tilt.

Kisspeptin/KISS1R Signaling Modulates Human Airway Smooth Muscle Cell Migration.

Airway remodeling is a cardinal feature of asthma, associated with increased airway smooth muscle cell (ASM) mass and up-regulation of extracellular matrix deposition. Exaggerated ASM cell migration contributes to excessive ASM mass. Previously, we demonstrated the alleviating role of kisspeptin (Kp) receptor (KISS1R) activation by Kp-10 in mitogen (PDGF)-induced human ASM cell proliferation in vitro and airway remodeling in vivo in a mouse model of asthma. Here, we examined the mechanisms by which KISS1R activation regulates mitogen-induced ASM cell migration. KISS1R activation using Kp-10 significantly inhibited PDGF-induced ASM cell migration, further confirmed using KISS1R shRNA. Furthermore, KISS1R activation modulated F/G actin dynamics and the expression of pro-migration proteins like cell division control protein 42 (CDC42) and cofilin. Mechanistically, we observed reduced ASM RhoA-GTPAse with KISS1R activation. The anti-migratory effect of KISS1R was abolished by protein kinase A (PKA)-inhibitory peptide. Conversely, KISS1R activation significantly increased cAMP and phosphorylation of cAMP-response element binding protein (CREB) in PDGF-exposed ASM cells. Overall, these results highlight the alleviating properties of Kp-10 in the context of airway remodeling.

Association of Environmental Injustice and Cardiovascular Diseases and Risk Factors in the United States.

BACKGROUND: While the impacts of social and environmental exposure on cardiovascular risks are often reported individually, the combined effect is poorly understood. METHODS AND RESULTS: Using the 2022 Environmental Justice Index, socio-environmental justice index and environmental burden module ranks of census tracts were divided into quartiles (quartile 1, the least vulnerable census tracts; quartile 4, the most vulnerable census tracts). Age-adjusted rate ratios (RRs) of coronary artery disease, strokes, and various health measures reported in the Prevention Population-Level Analysis and Community Estimates data were compared between quartiles using multivariable Poisson regression. The quartile 4 Environmental Justice Index was associated with a higher rate of coronary artery disease (RR, 1.684 [95% CI, 1.660-1.708]) and stroke (RR, 2.112 [95% CI, 2.078-2.147]) compared with the quartile 1 Environmental Justice Index. Similarly, coronary artery disease 1.057 [95% CI,1.043-1.0716] and stroke (RR, 1.118 [95% CI, 1.102-1.135]) were significantly higher in the quartile 4 than in the quartile 1 environmental burden module. Similar results were observed for chronic kidney disease, hypertension, diabetes, obesity, high cholesterol, lack of health insurance, sleep <7 hours per night, no leisure time physical activity, and impaired mental and physical health >14 days. CONCLUSIONS: The prevalence of CVD and its risk factors is highly associated with increased social and environmental adversities, and environmental exposure plays an important role independent of social factors.

Toxic heavy metal ions contamination in water and their sustainable reduction by eco-friendly methods: isotherms, thermodynamics and kinetics study.

Heavy metal ions can be introduced into the water through several point and non-point sources including leather industry, coal mining, agriculture activity and domestic waste. Regrettably, these toxic heavy metals may pose a threat to both humans and animals, particularly when they infiltrate water and soil. Heavy metal poisoning can lead to many health complications, such as liver and renal dysfunction, dermatological difficulties, and potentially even malignancies. To mitigate the risk of heavy metal ion exposure to humans and animals, it is imperative to extract them from places that have been polluted. Several conventional methods such as ion exchange, reverse osmosis, ultrafiltration, membrane filtration and chemical precipitation have been used for the removal of heavy metal ions. However, these methods have high operation costs and generate secondary pollutants during water treatment. Biosorption is an alternative approach to eliminating heavy metals from water that involves employing eco-friendly and cost-effective biomass. This review is focused on the heavy metal ions contamination in the water, biosorption methods for heavy metal removal and mathematical modeling to explain the behaviour of heavy metal adsorption. This review can be helpful to the researchers to design wastewater treatment plants for sustainable wastewater treatment.

Epstein-Barr virus gp42 antibodies reveal sites of vulnerability for receptor binding and fusion to B cells.

Epstein-Barr virus (EBV) causes infectious mononucleosis and is associated with B cell lymphomas. EBV glycoprotein 42 (gp42) binds HLA class II and activates membrane fusion with B cells. We isolated gp42-specific monoclonal antibodies (mAbs), A10 and 4C12, which use distinct mechanisms to neutralize virus infection. mAb A10 was more potent than the only known neutralizing gp42 mAb, F-2-1, in neutralizing EBV infection and blocking binding to HLA class II. mAb 4C12 was similar to mAb A10 in inhibiting glycoprotein-mediated B cell fusion but did not block receptor binding, and it was less effective in neutralizing infection. Crystallographic structures of gH/gL/gp42/A10 and gp42/4C12 complexes revealed two distinct sites of vulnerability on gp42 for receptor binding and B cell fusion. Passive transfer of mAb A10 into humanized mice conferred nearly 100% protection from viremia and EBV lymphomas after EBV challenge. These findings identify vulnerable sites on EBV that may facilitate therapeutics and vaccines.

Integrative experimental validation of concomitant miRNAs and transcription factors with differentially expressed genes in acute myocardial infarction.

Identification of concomitant miRNAs and transcription factors (TFs) with differential expression (DEGs) in MI is crucial for understanding holistic gene regulation, identifying key regulators, and precision in biomarker and therapeutic target discovery. We performed a comprehensive analysis using Affymetrix microarray data, advanced bioinformatic tools, and experimental validation to explore potential biomarkers associated with human pathology. The search strategy includes the identification of the GSE83500 dataset, comprising gene expression profiles from aortic wall punch biopsies of MI and non-MI patients, which were used in the present study. The analysis identified nine distinct genes exhibiting DEGs within the realm of MI. miRNA-gene/TF and TF-gene/miRNA regulatory relations were mapped to retrieve interacting hub genes to acquire an MI miRNA-TF co-regulatory network. Furthermore, an animal model of I/R-induced MI confirmed the involved gene based on quantitative RT-PCR and Western blot analysis. The consequences of the bioinformatic tool substantiate the inference regarding the presence of three key hub genes (UBE2N, TMEM106B, and CXADR), a central miRNA (hsa-miR-124-3p), and sixteen TFs. Animal studies support the involvement of predicted genes in the I/R-induced myocardial infarction assessed by RT-PCR and Western blotting. Thus, the final consequences suggest the involvement of promising molecular pathways regulated by TF (p53/NF-κB1), miRNA (hsa-miR-124-3p), and hub gene (UBE2N), which may play a key role in the pathogenesis of MI.

Matched dielectric slot waveguide as an all-dielectric terahertz magnetic dipole.

We observe that the modal field distribution of a dielectric slot waveguide closely resembles a magnetic dipole antenna. Such an aperture distribution traditionally demands metals, making it ill-suited to high frequencies due to excessive ohmic loss. By terminating a dielectric slot waveguide with a matched free-space interface, a compact all-dielectric radiating magnetic dipole is realized. In this way, we introduce general-purpose dipole antennas, which have long been a mainstay of RF and microwave ranges, into the realm of light wave photonic integrated circuits. The existence of the desired magnetic dipole aperture distribution is experimentally confirmed in the terahertz range, at ∼275 GHz, and good matching is evident in the ∼-25 dB reflection level. This is the electrically smallest radiator to ever be incorporated into an all-dielectric waveguiding platform.

Amelioration of endothelial integrity by 3,5,4'-trihydroxy-trans-stilbene against high-fat-diet-induced obesity and -associated vasculopathy and myocardial infarction in rats, targeting TLR4/MyD88/NF-κB/iNOS signaling cascade.

Exacerbated expression of TLR4 protein (foremost pattern recognition receptor) during obesity could trigger NF-κB/iNOS signaling through linker protein (MyD88), predisposed to an indispensable inflammatory response. The induction of this detrimental cascade leads to myocardial and vascular abnormalities. Molecular docking was studied for protein-ligand interaction between these potential targets and resveratrol. The pre-treatment of resveratrol (20 mg/kg/p.o/per day for ten weeks) was given to investigate the therapeutic effect against HFD-induced obesity and associated vascular endothelial dysfunction (VED) and myocardial infarction (MI) in Wistar rats. In addition to accessing the levels of serum biomarkers for VED and MI, oxidative stress, inflammatory cytokines, and histopathology of these tissues were investigated. Lipopolysaccharide (for receptor activation) and protein expression analysis were introduced to explore the mechanistic involvement of TLR4/MyD88/NF-κB/iNOS signaling. Assessment of in-silico analysis showed significant interaction between protein and ligand. The involvement of this proposed signaling (TLR4/MyD88/NF-κB/iNOS) was further endorsed by the impact of lipopolysaccharide and protein expression analysis in obese and treated rats. Moreover, resveratrol pre-treated rats showed significantly lowered cardio and vascular damage measured by the distinct down expression of the TLR4/MyD88/NF-κB/iNOS pathway by resveratrol treatment endorses its ameliorative effect against VED and MI.

A Bayesian meta-analysis of double kissing (DK) crush or provisional stenting for coronary artery bifurcation lesions.

OBJECTIVE: Despite the development of dedicated, two-stent strategies, including the double kissing (DK) crush technique, the ideal technique for coronary artery bifurcation stenting has not been identified. We aimed to compare and determine the absolute risk difference (ARD) of the DK crush technique alone versus provisional stenting approaches for coronary bifurcation lesions, using the Bayesian technique. METHOD: We queried PubMed/MEDLINE to identify randomized controlled trials (RCTs) that compared DK crush technique with provisional stenting for bifurcation lesions, published till January 2023. We used Bayesian methods to calculate the ARD and 95% credible interval (CrI). RESULTS: We included three RCTs, with 916 patients, in the final analysis. The ARD of cardiac death was centered at -0.01 (95% CrI: -0.04 to 0.02; Tau: 0.02, 85% probability of ARD of DK crush vs. provisional stenting <0). ARD for myocardial infarction was centered at -0.03 (95%CrI: -0.9 to 0.03; Tau: 0.05, 87% probability of ARD of DK crush vs. provisional stenting <0). ARD for stent thrombosis was centered at 0.00 (95% CrI: -0.04 to 0.03, Tau: 0.03, 51% probability of ARD for DK crush vs. provisional stenting <0). Finally, ARD for target lesion revascularization was centered at -0.05 (95% CrI: -0.08 to -0.03, Tau: 0.02, 99.97% probability of ARD for DK crush vs. provisional stenting <0). CONCLUSIONS: Bayesian analysis demonstrated a lower probability of cardiac death, myocardial infarction and target lesion revascularization, with DK crush compared with provisional stenting techniques, and a minimal probability of difference in stent thrombosis.

Experimental and computational studies on the corrosion inhibition potential of a novel synthesized thiophene and pyridine-based 1,3,4-oxadiazole hybrid against mild steel corrosion in 1 N HCl.

A convenient synthesis of a novel 1,3,4-oxadiazole derivative, specifically known as, 2-(5-methylthiophen-2-yl)-5-(pyridin-3-yl)-1,3,4-oxadiazole (MTPO), is reported along with a comprehensive evaluation of its ability to inhibit the corrosion of mild steel (MS) in a 1 N HCl environment using weight loss, EIS, PDP, SEM, EDX, and UV-Vis spectroscopy. The investigated inhibitor expressed excellent inhibition efficiency (99.05% at 500 ppm, 298 K) with a mixed-type inhibitory mechanism as demonstrated by the PDP technique. Furthermore, MTPO followed Langmuir adsorption isotherm, which provides insights into the adsorption phenomena, demonstrating that it exhibits superior adsorption behavior on the MS surface compared. In silico investigations, using DFT computation and MD simulation complements the experimental outcomes revealing strong adsorbing attributes of the MTPO hybrid with the ω - and ω + values of 8.8882 eV and 4.4787 eV, respectively. In addition, the radial distribution function also addressed the chemisorption behavior of MTPO. This article also takes into consideration the various ways in which the inhibitor interacts with the mild steel, offering potential insights for developing strategies to mitigate metal dissolution in acidic environments.

Ammonia is associated with liver-related complications and predicts mortality in acute-on-chronic liver failure patients.

The relationship between ammonia and liver-related complications (LRCs) in acute-on-chronic liver failure (ACLF) patients is not clearly established. This study aimed to evaluate the association between ammonia levels and LRCs in patients with ACLF. The study also evaluated the ability of ammonia in predicting mortality and progression of LRCs. The study prospectively recruited ACLF patients based on the APASL definition from the ACLF Research Consortium (AARC) from 2009 to 2019. LRCs were a composite endpoint of bacterial infection, overt hepatic encephalopathy (HE), and ascites. A total of 3871 cases were screened. Of these, 701 ACLF patients were enrolled. Patients with LRCs had significantly higher ammonia levels than those without. Ammonia was significantly higher in patients with overt HE and ascites, but not in those with bacterial infection. Multivariate analysis found that ammonia was associated with LRCs. Additionally, baseline arterial ammonia was an independent predictor of 30-day mortality, but it was not associated with the development of new LRCs within 30 days. In summary, baseline arterial ammonia levels are associated with 30-day mortality and LRCs, mainly overt HE and ascites in ACLF patients.

Laser-Induced Intracellular Delivery: Exploiting Gold-Coated Spiky Polymeric Nanoparticles and Gold Nanorods under Near-Infrared Pulses for Single-Cell Nano-Photon-Poration.

This study explores the potential of laser-induced nano-photon-poration as a non-invasive technique for the intracellular delivery of micro/macromolecules at the single-cell level. This research proposes the utilization of gold-coated spiky polymeric nanoparticles (Au-PNPs) and gold nanorods (GNRs) to achieve efficient intracellular micro/macromolecule delivery at the single-cell level. By shifting the operating wavelength towards the near-infrared (NIR) range, the intracellular delivery efficiency and viability of Au-PNP-mediated photon-poration are compared to those using GNR-mediated intracellular delivery. Employing Au-PNPs as mediators in conjunction with nanosecond-pulsed lasers, a highly efficient intracellular delivery, while preserving high cell viability, is demonstrated. Laser pulses directed at Au-PNPs generate over a hundred hot spots per particle through plasmon resonance, facilitating the formation of photothermal vapor nanobubbles (PVNBs). These PVNBs create transient pores, enabling the gentle transfer of cargo from the extracellular to the intracellular milieu, without inducing deleterious effects in the cells. The optimization of wavelengths in the NIR region, coupled with low laser fluence (27 mJ/cm2) and nanoparticle concentrations (34 µg/mL), achieves outstanding delivery efficiencies (96%) and maintains high cell viability (up to 99%) across the various cell types, including cancer and neuronal cells. Importantly, sustained high cell viability (90-95%) is observed even 48 h post laser exposure. This innovative development holds considerable promise for diverse applications, encompassing drug delivery, gene therapy, and regenerative medicine. This study underscores the efficiency and versatility of the proposed technique, positioning it as a valuable tool for advancing intracellular delivery strategies in biomedical applications.