Maximum Efficacy Research Articles

Successful one-stage surgical repair in a rare adult patient with berry syndrome.

Berry syndrome is a rare congenital cardiac malformation, herein we report an adult male patient who was successfully repaired by one-stage surgery. 18-year-old male patient presenting symptoms of chest tightness and shortness for over a year presented to outpatient clinic in our department to have corrective procedure heart. CTA revealed an Aortopulmonary Window (APW) type III, measuring 4.6 cm in maximum diameter. The right pulmonary artery originated from the ascending aorta, and the pulmonary trunk exhibited dilation with dimensions of 8.3 cm × 5.7 cm × 5.9 cm. Additional findings included Interrupted Aortic Arch (IAA) type A, intact ventricular septum, and Patent Ductus Arteriosus (PDA). Echocardiography showed bidirectional shunt at the level of APW in severe pulmonary hypertension. The right heart catheterization indicated a mean pulmonary artery pressure of 70mmHg and a pulmonary artery resistance of 5 Wood units. We evaluated after two weeks of treatment with epoprostenol at a rate of 20 ng/(kg. min) and found a significant improvement in pulmonary-artery pressure. Finally, we communicated with the patient's family and decided to proceed with the procedure. For complex cardiovascular malformations, the ideal treatment strategy must be tailored to the characteristics of the patient to provide maximum efficacy and safety.

Therapeutic Intervention of Serine Protease Inhibitors against Hepatitis C Virus.

Hepatitis C virus (HCV) is a globally prevalent and hazardous disorder that is responsible for inducing several persistent and potentially fatal liver diseases. Current treatment strategies offer limited efficacy, often accompanied by severe and debilitating adverse effects. Consequently, there is an urgent and compelling need to develop novel therapeutic interventions that can provide maximum efficacy in combating HCV while minimizing the burden of adverse effects on patients. One promising target against HCV is the NS3-4A serine protease, a complex composed of two HCV-encoded proteins. This non-covalent heterodimer is crucial in the viral life cycle and has become a primary focus for therapeutic interventions. Although peginterferon, combined with ribavirin, is commonly employed for HCV treatment, its efficacy is hampered by significant adverse effects that can profoundly impact patients' quality of life. In recent years, the development of direct-acting antiviral agents (DAAs) has emerged as a breakthrough in HCV therapy. These agents exhibit remarkable potency against the virus and have demonstrated fewer adverse effects when combined with other DAAs. However, it is important to note that there is a potential for developing resistance to DAAs due to alterations in the amino acid position of the NS3-4A protease. This emphasizes the need for ongoing research to identify strategies that can minimize the emergence of resistance and ensure long-term effectiveness. While the combination of DAAs holds promise for HCV treatment, it is crucial to consider the possibility of drug-drug interactions. These interactions may occur when different DAAs are used concurrently, potentially compromising their therapeutic efficacy. Therefore, carefully evaluating and monitoring potential drug interactions are vital to optimize treatment outcomes. In the pursuit of novel therapeutic interventions for HCV, the field of computational biology and bioinformatics has emerged as a valuable tool. These advanced technologies and methodologies enable the development and design of new drugs and therapeutic agents that exhibit maximum efficacy, reduced risk of resistance, and minimal adverse effects. By leveraging computational approaches, researchers can efficiently screen and optimize potential candidates, accelerating the discovery and development of highly effective treatments for HCV, treatments.

Polypyrrole-encapsulated metal oxide nanocomposite for adsorptive abatement of anionic dye from dye laden wastewater: Cost analysis and scale up design

The present work demonstrates the fabrication of an organometallic material i.e. polypyrrole-encapsulated zinc oxide (PPy@ZnO) nanocomposite for adsorptive elimination of Eriochrome black-T (EBT) dye from water. The specific surface area and pore volume of the PPy@ZnO nanocomposite were observed to be 28.726 m2/g and 0.086 cc/g, respectively. At optimum experimental conditions of solution pH; 4.0, PPy@ZnO nanocomposite dose: 1.0 g/L, contact time: 30 min and initial EBT dye concentration: 50 mg/L, maximum EBT dye removal efficiency of ∼94±1.86% was obtained. The pseudo-second-order kinetic and Langmuir isotherm model provides the best fit for the adsorption experiments, with maximum EBT dye adsorption capacity of 277.78 mg/g. The prominent adsorption mechanisms include the hydrogen bonding, π–π interactions, and electrostatic attraction. The adsorption study is spontaneous (ΔG° < 0) and endothermic (ΔH° > 0, ΔS° > 0) in nature as indicated by the thermodynamics study. The reduction in EBT dye removal efficiency was insignificant (∼10±0.94%) in surface water as compared to other real water samples. Monovalent anions (i.e., NO3–and Cl–) have minimal impact on EBT removal efficiency with reduction in removal efficiencies in the range of 4.0±1.54% to ∼11.0±1.93%. Regeneration study suggests an overall ∼20±1.45% decrease in the EBT dye removal efficiency after 5th cycle of regeneration. Response surface methodology suggests the maximum adsorption efficacy of 95±1.68% at initial EBT dye concentration of 35 mg/L, PPy@ZnO dose of 0.85 g/L and contact time of 40 min. The estimated synthesis cost of PPy@ZnO nanocomposite was determined to be ∼117 USD/kg. Batch mode scale-up design suggests a minimum of 87.48 g of PPy@ZnO nanocomposite needs to be applied to treat 50 mg/L of EBT dye loaded wastewater (50 L volume) with 95% dye removal efficiency.

Antimicrobial Ionic Liquids: Ante-Mortem Mechanisms of Pathogenic EPEC and MRSA Examined by FTIR Spectroscopy.

Ionic liquids (ILs) have gained considerable attention due to their versatile and designable properties. ILs show great potential as antibacterial agents, but understanding the mechanism of attack on bacterial cells is essential to ensure the optimal design of IL-based biocides. The final aim is to achieve maximum efficacy while minimising toxicity and preventing resistance development in target organisms. In this study, we examined a dose-response analysis of ILs' antimicrobial activity against two pathogenic bacteria with different Gram types in terms of molecular responses on a cellular level using Fourier-transform infrared (FTIR) spectroscopy. In total, 18 ILs with different antimicrobial active motifs were evaluated on the Gram-negative enteropathogenic Escherichia coli (EPEC) and Gram-positive methicillin-resistant Staphylococcus aureus (MRSA). The results showed that most ILs impact bacterial proteins with increasing concentration but have a minimal effect on cellular membranes. Dose-response spectral analysis revealed a distinct ante-mortem response against certain ILs for MRSA but not for EPEC. We found that at sub-lethal concentrations, MRSA actively changed their membrane composition to counteract the damaging effect induced by the ILs. This suggests a new adaptive mechanism of Gram-positive bacteria against ILs and demonstrates the need for a better understanding before using such substances as novel antimicrobials.

Modeling an evaluation of the efficacy of the novel neuroanalgesic drug mirogabalin for diabetic peripheral neuropathic pain and postherpetic neuralgia therapy

Diabetic peripheral neuropathic pain (DPNP) and postherpetic neuralgia (PHN) are challenging and often intractable complex medical conditions, with a substantial impact on the quality of life. Mirogabalin, a novel voltage-gated Ca2+ channel α2δ ligand, was approved for the indication of DPNP and PHN. However, the time course of effects has not yet been clarified.We aimed to establish pharmacodynamic and placebo effect models of mirogabalin and pregabalin in DPNP and PHN, and to quantitatively compare the efficacy characteristics (maximum efficacy, onset time, and other pharmacodynamic parameters) and safety of mirogabalin and pregabalin. Public databases were comprehensively searched for randomized placebo-controlled clinical trials. A model-based meta-analysis (MBMA) was developed to describe the time course of drug efficacy and placebo effects. Adverse events were compared using a fixed-effects meta-analysis. Sixteen studies including 5,147 participants were eligible for this study. The placebo effect was relatively high and gradually increased with time, and it required at least eight weeks to reach a plateau. The pharmacodynamic model revealed that the maximum pure efficacy for mirogabalin and pregabalin was approximately -7.85 % and -8.86 %, respectively; the efficacy of mirogabalin to relieve DPNP and PHN was not superior to that of pregabalin, and both drugs had similar safety. While the rate constant of the onset rate of pregabalin was approximately thrice as high as that of mirogabalin. In addition, the baseline level of pain was an important factor affecting pregabalin efficacy. These findings are helpful in evaluating the clinical extension value of mirogabalin. They suggest that the high placebo effect and the baseline level of pain should be considered when grouping patients in future research and development of voltage-gated Ca2+ channel neuroanalgesic.

Fabrication and application of targeted ciprofloxacin nanocarriers for the treatment of chronic bacterial prostatitis

Pathogenic bacteria cause chronic bacterial prostatitis (CBP). CPB is characterized by urinary tract infection and persistence of pathogenic bacteria in prostatic secretion. Owing to poor blood supply to the prostate gland and limited drug penetration, CBP treatment is difficult. Transferosomes are ultradeformable vesicles for nanocarrier applications, which have become an important area of nanomedicine. Such carriers are specifically targeted to the pathological area to provide maximum therapeutic efficacy. It consists of a lipid bilayer soybean lecithin phosphatidylcholine (PC), an edge activator Tween 80 with various ratios, and a chloroform/methanol core. Depending on the lipophilicity of the active substance, it can be encapsulated within the core or among the lipid bilayer. Due to their exceptional flexibility, which enables them to squeeze themselves through narrow pores that are significantly smaller than their size, they can be a solution. One formulation (Cipro5 PEG) was selected for further in vitro analysis and was composed of phosphatidylcholine (PC), Tween 80, and polyethylene glycol-6 stearate (PEG-6 stearate) in a ratio of 3:3:1 in a chloroform/methanol mixture (1:2 v/v). In vitro, the results showed that PEGylated transferosomes had faster drug release, higher permeation, and increased bioavailability. The transferosomes were quantified with a particle size of 202.59 nm, a zeta potential of-49.38 mV, and a drug entrapment efficiency of 80.05%. The aim of this study was to investigate drug targeting. Therefore, Monoclonal antibody IgG was coupled with Cipro5 PEG, which has specificity and selectivity for conjugated nanoparticles. In vivo, a total of twenty-five adult Wistar rats were obtained and randomly divided into 5 groups, each of 5 rats at random: the control group, blank group, positive control group, Cipro 5PEG group, and Cipro 5PEG coupled with IgG antibody group. The cytokines levels (IL-1β, IL-8, and TNF-α) in the serum were detected by analysis kits. Compared with the control group, treatment with Cipro 5PEG coupled with the IgG antibody could significantly inhibit cytokines, according to histological analysis. Cipro 5PEG, coupled with the IgG antibody group, reduced prostate tissue inflammation. Hence, our results show a promising approach to delivering antibiotics for the targeted therapy of CBP.

Novel Ganga-sand-encapsulated polyaniline granules for effective remediation of textile and pharmaceutical wastewater

ABSTRACT This study presents the use of novel Ganga-sand-encapsulated polyaniline granules for effective remediation of textile and pharmaceutical wastewater. The prepared Ganga-sand-encapsulated polyaniline granules were characterised using scanning electron microscope (morphology) and Fourier transform infrared techniques. The effect of adsorbent dose, contact time, pH and concentration influence on the adsorption performance of Ganga-sand-encapsulated polyaniline granules for the removal of methylene blue dye (textile waste) and doxycycline antibiotic (pharmaceutical waste) was studied. Kinetic and isotherm studies were also carried out to investigate the adsorption process further. The maximum adsorptive removal efficacy of methylene blue and doxycycline was found as 98.2% and 85.1%, respectively, at the optimised condition of adsorbent dose: 8 g/L, time: 120 min, pH: 12 and concentration: 50 ppm. From adsorption kinetics, it was established that the adsorption process followed pseudo-second-order (PSO) rather than pseudo-first-order (PFO). The correlation coefficient values for PFO and PSO models were 0.9012 and 0.9992, respectively, for methylene blue dye adsorption on Ganga-sand-encapsulated polyaniline granules. The adsorption isotherm study established that the adsorption process followed the Langmuir model rather than the Freundlich model. This study found that Ganga-sand-encapsulated polyaniline granules can be a promising adsorbent for textile and pharmaceutical wastewater treatment.

COMPARATIVE EFFICACY OF NEEM OIL DERIVATIVES WITH IMIDACLOPRID AGAINST OKRA JASSID, AMRASCA BIGUTTULA (ISHIDA)

The present research study was conducted at the experimental field condition of Pakistan Agricultural Research Council, Southern Zone Agricultural Research Centre, University of Karachi, to compare the field performance of different neem oil derivatives doses with Imidacloprid, sprayed on okra crop against the jassid population. The experiments were carried out RCBD with the application of four treatments, including three different concentrations of neem oils at (2%, 1.5%, and 1%) with the comparison of Imidacloprid pesticide and control. Neem oil was selected as a natural pesticide against jassid population reduction on okra crop. All the treatments were sprayed twice and data were recorded before 24h of pre-treatment and post-treatment at 48h, 72h, and 144h, respectively. The overall maximum reduction % after the application of Imidacloprid against the jassid population was calculated (61.51%) in 1st spray and (58.25%) 2nd spray, followed by (43.01%), (39.75%) at 2%, consequent to (32.50%), (29.75%), at 1.5% and (25.55%), (24.52%) at 1%, respectively. The maximum efficacy in neem oil concentration was recorded at 2% followed by 1.5%, and 1% but all neem oil concentrations including Imidacloprid observed effective from the 1st day up to the 6th post-spray days. All neem oil concentrations after 24h, 48h, 72h, and 144h of post-spray found significantly different at (P&lt; 0.05). The application of neem oil, 2% caused the phytotoxicity reduction in okra plants. Thus, it is recommended that the bio-pesticide should be applied at 1.5% neem oil concentration against the jassid pest population.

High-Dose Isoniazid Lacks EARLY Bactericidal Activity against Isoniazid-resistant Tuberculosis Mediated by katG Mutations: A Randomized Phase II Clinical Trial.

Rationale: Observational studies suggest that high-dose isoniazid may be efficacious in treating multidrug-resistant tuberculosis. However, its activity against Mycobacterium tuberculosis (M.tb) with katG mutations (which typically confer high-level resistance) is not established. Objectives: To characterize the early bactericidal activity (EBA) of high-dose isoniazid in patients with tuberculosis caused by katG-mutated M.tb. Methods: A5312 was a phase IIA randomized, open-label trial. Participants with tuberculosis caused by katG-mutated M.tb were randomized to receive 15 or 20 mg/kg isoniazid daily for 7 days. Daily sputum samples were collected for quantitative culture. Intensive pharmacokinetic sampling was performed on Day 6. Data were pooled across all A5312 participants for analysis (drug-sensitive, inhA-mutated, and katG-mutated M.tb). EBA was determined using nonlinear mixed-effects modeling. Measurements and Main Results: Of 80 treated participants, 21 had katG-mutated M.tb. Isoniazid pharmacokinetics were best described by a two-compartment model with an effect of NAT2 acetylator phenotype on clearance. Model-derived maximum concentration and area under the concentration-time curve in the 15 and 20 mg/kg groups were 15.0 and 22.1 mg/L and 57.6 and 76.8 mg ⋅ h/L, respectively. Isoniazid bacterial kill was described using an effect compartment and a sigmoidal maximum efficacy relationship. Isoniazid potency against katG-mutated M.tb was approximately 10-fold lower than in inhA-mutated M.tb. The highest dose of 20 mg/kg did not demonstrate measurable EBA, except against a subset of slow NAT2 acetylators (who experienced the highest concentrations). There were no grade 3 or higher drug-related adverse events. Conclusions: This study found negligible bactericidal activity of high-dose isoniazid (15-20 mg/kg) in the majority of participants with tuberculosis caused by katG-mutated M.tb. Clinical trial registered with www.clinicaltrials.gov (NCT01936831).

In vitro photoinactivation of Pseudomonas aeruginosa and Staphylococcus aureus biofilm by a novel multi-dose LED-based illumination method

Significancerecently, an aerosolized light source has been proposed to photo-inactivate pathogens responsible for multidrug-resistant chronic lung infections. To maximize the light source in vivo photokilling efficacy, its emission spectrum was predicted by a semi-theoretical model. To confirm and upgrade the model with experiments, biofilm photoinactivation studies were performed. Approachin vitro biofilms of P. aeruginosa and S. aureus (reference and clinical strains) were photo-inactivated by LED sources at 415, 445, 525 and 623nm. Non-uniform illumination protocol was employed to deliver different doses (10 to 110 J/cm2) in a single experiment. Photokilling efficacy was quantified by CFU counting. Results415nm-peaked light was associated with the maximum photokilling efficacy for all the considered strains. Other wavelengths have a minor or scant effect. Conclusionsbiofilm photoinactivation was studied as a function of both dose and illumination wavelength. Results are compatible with expected presence of endogenous photosensitizers (porphyrins) in the bacteria.

Using an App-Based Mindfulness Intervention: A Mixed Methods Approach

Mindfulness-based practices are often utilized and substantial research supports the continued use of these practices as effective interventions. Mindfulness interventions that utilize focused breathing, app-based guidance, and brief duration may present mental health benefits. However, examining individuals’ unique experiences from continued engagement in brief app-based mindfulness interventions over time, as well as identifying potential barriers preventing the use, is understudied. The current study utilized a longitudinal mixed method design to understand the experiences of individuals using a widely available app-based (i.e., Apple Watch) mindfulness breathing intervention over a 2-week period by identifying the thematic patterns common among the individuals and how this affected their levels of depression, anxiety, and coping skills over time. Qualitative analysis revealed a general positive experience among the participants, as well as the importance of personalization related to mindfulness interventions. Quantitative findings indicated a significant increase in coping skills, but no substantial change in their levels of depression or anxiety after 2 weeks. Researchers should continue examining interventions that include the core aspects of mindfulness, while exploring variations of mindfulness duration, frequency, total length, and breath rate to determine maximum efficacy. Practice-based interventions should focus on the effective ways to implement app-based self-guided mindfulness interventions, such as being short in duration, personalized for daily use, and aligning the practice with key components of mindfulness.

Evaluating Rhizobacterial Antagonists for Controlling Cercospora beticola and Promoting Growth in Beta vulgaris.

Cercospora beticola Sacc. is an ascomycete pathogen that causes Cercospora leaf spot in sugar beets (Beta vulgaris L.) and other related crops. It can lead to significant yield losses if not effectively managed. This study aimed to assess rhizosphere bacteria from sugar beet soil as a biological control agent against C. beticola and evaluate their effect on B. vulgaris. Following a dual-culture screening, 18 bacteria exhibiting over 50% inhibition were selected, with 6 of them demonstrating more than 80% control. The bacteria were identified by sequencing the 16S rRNA gene, revealing 12 potential species belonging to 6 genera, including Bacillus, which was represented by 4 species. Additionally, the biochemical and molecular properties of the bacteria were characterized in depth, as well as plant growth promotion. PCR analysis of the genes responsible for producing antifungal metabolites revealed that 83%, 78%, 89%, and 56% of the selected bacteria possessed bacillomycin-, iturin-, fengycin-, and surfactin-encoding genes, respectively. Infrared spectroscopy analysis confirmed the presence of a lipopeptide structure in the bacterial supernatant filtrate. Subsequently, the bacteria were assessed for their effect on sugar beet plants in controlled conditions. The bacteria exhibited notable capabilities, promoting growth in both roots and shoots, resulting in significant increases in root length and weight and shoot length. A field experiment with four bacterial candidates demonstrated good performance against C. beticola compared to the difenoconazole fungicide. These bacteria played a significant role in disease control, achieving a maximum efficacy of 77.42%, slightly below the 88.51% efficacy attained with difenoconazole. Additional field trials are necessary to verify the protective and growth-promoting effects of these candidates, whether applied individually, combined in consortia, or integrated with chemical inputs in sugar beet crop production.

Abstract 2462: Live attenuated Salmonella ZH9 as novel microbial immunotherapy for the treatment of bladder cancer

Abstract Microbial immunotherapy with Bacillus Calmette-Guérin (BCG) has been the standard-of-care for non-muscle invasive bladder cancer (NMIBC) for over 30 years. Today, global demand for BCG exceeds supply, leaving many patients untreated. BCG is associated with high disease recurrence and presents high treatment burden for patients. There remains therefore significant unmet need for novel therapeutic approaches for NMIBC and we sought to establish the utility of the live-attenuated Salmonella enterica Typhi ZH9 as a more effective microbial immunotherapy. Efficacy of ZH9 was established in orthotopic, syngeneic, mouse MB49 tumor models in which animals were treated in the bladder via catheterization, with or without prior subcutaneous immune priming. Immune responses were measured by flow cytometry and Nanostring transcriptomic analyses of bladder tissues. An intravesical dose of ZH9 after orthotopic MB49 tumour inoculation demonstrated significant survival benefit compared to both vehicle control and equivalent colony forming unit (CFU) BCG treatments. Repeat, weekly dosing studies showed a single administration of ZH9 was sufficient for maximum efficacy. To explore the durability of protection, surviving intravesical ZH9 treated animals were rechallenged, demonstrating protection from both bladder and subcutaneous MB49 tumors suggestive of lasting local and systemic anti-tumor immunity. Flow cytometry analysis of bladders showed that intravesical ZH9 treatment resulted in cellular immune response characterised by recruitment of NK cells, CD4+ and CD8+ T cells, and dendritic cells with an activated, cross-presenting phenotype, in all cases of greater magnitude than after treatment with an equivalent dose of BCG. Based on observations that pre-existing immunity to BCG has been associated with improved outcomes to intravesical BCG therapy in NMIBC, we explored whether systemic priming with ZH9 benefits local bladder therapy. Systemic prime with ZH9 followed by a single intravesical dose of ZH9 showed a trend for improved survival and will be explored in the clinical setting. This systemic immune priming effect was associated with enhanced local bladder immune cell infiltrates and the upregulation of more than 150 immune response genes in the bladder compared to intravesical therapy alone. These data form the basis of preclinical package accepted by the FDA for a Phase 1/1b study evaluating the safety, pharmacology, and clinical effect of ZH9 treatment in patients with NMIBC, currently recruiting patients. The investigation includes thorough translational and biomarker studies to delve into the mechanism of action of ZH9 and explore patient stratification approaches. By easing the treatment burden on patients, lowering healthcare costs, and featuring a scalable manufacturing process, ZH9 has the potential to revolutionize the treatment paradigm in NMIBC and reshape the patient journey. Citation Format: Nicholas Glanville, Oluwatobiloba Oke, Claudia Prevosto, Alexandra Sevko, Andrew Scott, Sonia Domingos-Pereira, Lenka Polak, Denise Nardelli-Haefliger, Livija Deban. Live attenuated Salmonella ZH9 as novel microbial immunotherapy for the treatment of bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2462.

Bioproduction, purification, partial characterization and phenol removal efficacy of tyrosinase enzyme from Streptomyces sp. strain MR28

The study focused on the production of the tyrosinase enzyme from Streptomyces sp. MR28 and its potency in removal of phenol content from water using free and immobilized tyrosinase enzyme. The tyrosinase was produced by Streptomyces sp. MR28 in liquid tyrosine broth medium, and it was further purified to near its homogeneity by employing, precipitation, dialysis, and column chromatography. After the purification, 44.49% yield with a 4 fold purification was achieved. The characterization of the purified enzyme showed a single major peak on HPLC and a solitary band on SDS-PAGE. The purified tyrosinase enzyme was active at a pH of 7.0 and a temperature of 30 °C. Further immobilization of purified tyrosinase was performed using the sodium alginate entrapment method. The capacity of the purified tyrosinase to remove phenol in water was evaluated by spectrophotometric method. The free tyrosinase enzyme-treated solutions showed a gradual decrease in the concentration of phenol with increased incubation time at 30 °C and 40 °C, at 90 min of the incubation time, it showed maximum efficacy in removing phenol from the solution. At 50 °C and 60 °C, the free tyrosinase enzyme exhibited very less capacity to remove the phenol. The immobilized enzyme showed good capacity for the removal of phenol from the solutions; the concentration of phenol in the solution decreased with an increase in the incubation time. At temperatures of 40 °C and 50 °C, the immobilized tyrosinase enzyme beads showed significant removal of phenol from the solution, and at temperatures of 30 °C and 60 °C, they also exhibited good capacity for the removal of phenol. At the end of the 90 min incubation period, it exhibited good capability. The current study suggests using immobilized microbial tyrosinase enzyme can be used for the removal of phenol from the contaminated water in a greener manner.

Active-transporting of charge-reversal Cu(II)-doped mesoporous silica nanoagents for antitumor chemo/chemodynamic therapy

Fe-based Fenton agents can generate highly reactive and toxic hydroxyl radicals (·OH) in the tumor microenvironment (TME) for chemodynamic therapy (CDT) with high specificity. However, the low pH environment and insufficient endogenous hydrogen peroxide (H2O2) of the highly efficient Fenton reaction limits its practical application in clinic. Here, a Cu(II)-doped mesoporous silica nanoagent (Cu-MSN) with excellent dispersity was successfully developed. After loaded with doxorubicin (DOX) and ascorbate (AA), Cu-MSN@DA was coated with active targeting ligand folic acid (FA), dimethyl maleic an-hydride (DMMA) and carboxymethyl chitosan (CMC) to obtain an active transporting nanoagent (FCDC@Cu-MSN@DA) with tunable charge-reversal property, which is more adaptable to the pH value of TME than Fe-based Fenton agents, and can self-supply exogenous H2O2 by ascorbate to produce more toxic ·OH to trigger the apoptosis of cancer cells. Meanwhile, the high level of glutathione (GSH) in TME can reduce Cu(II) to Cu(I) by Fenton-like reaction, increasing the generation rate of ·OH and relieving tumor antioxidant ability. The supply of exogenous H2O2 significantly enhanced the synergistic effect of CDT by oxidative damage. Together with DOX-induced cell apoptosis, this novel nanoagent FCDC@Cu-MSN@DA can achieve maximum therapeutic efficacy, creating a new model of safe and effective tumor treatment with high specificity.

Corrosion inhibition of carbon steel by eucalyptus leaves in acidic media: An overview

This paper concerns the overview of previous studies on the corrosion and inhibition of carbon steel that is allowed to degrade in a corrosive medium by the extract of the eucalyptus plant, with an emphasis on the extract's adsorption behaviour. Many researchers have largely employed eucalyptus plant bark, oil, and leaf extracts to prevent the corrosion of mild steel in acidic environments under various temperature settings. According to the results, when the bark extract of the eucalyptus plant was added to HCl (5%) at a concentration of 900 ppm, the inhibitor's maximum efficiency was 98.2 %. The leaf extract, on the other hand, had the maximum inhibitory efficacy of 93.09 % at 600 mg/L extract concentration in the H2SO4 (0.5 M) medium. The extracts' potency was shown to diminish with increasing temperature. The mechanism for eucalyptus extract's protection of carbon steel from corrosion in diverse corrosive situations was largely associated with the adsorption of the extract's inhibitive components on the steel's surface to reduce the interaction between the metal and the corrosive surroundings. The majority of the reported inhibitive behaviour of the eucalyptus extract was consistent with the Langmuir adsorption isotherm model.

Evaluation of Carbonized Corncobs for Removal of Microcystins and Nodularin-R from Water

Microcystins (MCs) and nodularins (NODs) are cyanotoxins that can be found in water bodies during cyanobacterial harmful algal blooms (cyanoHABs). Consumption of water contaminated with cyanotoxins leads to health risks for humans and animals. Herein, corncob-based biochar and activated carbon (AC) were initially investigated for the sorption of six common MC congeners (MC-RR, MC-YR, MC-LR, MC-LA, MC-LW, and MC-LF) and nodularin-R (NOD-R) from spiked water. Biochar was prepared by refluxing commercial corncob with HCl and heating it to 250, 300, or 350 °C. AC was prepared by chemical activation of corncob with H3PO4 at 500 °C under a nitrogen atmosphere. Low-temperature nitrogen adsorption measurements confirmed that H3PO4-AC has a higher specific surface area (≈1100 m2/g) and total pore volume (≈0.75 cm3/g) than biochar and commercial AC. H3PO4-AC showed the maximum efficacy, among all corncob-based sorbents, to remove MCs and NOD-R from water as confirmed by experiments that involved sample analyses by ultrahigh-pressure liquid chromatography-mass spectrometry (UHPLC-MS). The effect of natural organic matter (NOM) on the adsorption of MCs was checked by incubating sorbents with Lake Erie water collected during cyanoHABs from 2020 to 2022. The total concentration (extracellular and intracellular) of studied MC congeners ranged from 1.37 µg/L to 438.51 µg/L and 50 mg of H3PO4-AC completely removed them from 3 mL of lake water. The effect of water pH on cyanotoxin adsorption was studied at pH values of 5.5, 7.0, and 8.5 at both a lower (10 μg/L each) and a higher (50 μg/L each) toxin concentration. Removal was influenced by solution pH at both concentrations when using biochar, while only at higher toxin concentration when using H3PO4-AC. At higher MC and NOD-R concentrations, competitive adsorption was prominent, and overall, the adsorption increased at acidic pH (5.5). The study results suggest that processed corncobs can remove a significant amount of MCs and NOD-R from water, and the measured sorption capacity of H3PO4-AC was ~20 mg of MC-LR and NOD-R per g of this sorbent.

Advantages of IL-17 inhibitor, ixekizumab, in the treatment of severe psoriasis

Psoriasis is a common immune-mediated disease, often accompanied by inflammatory and metabolic disorders. About 20–30% of patients have moderate to severe psoriasis and require systemic methods of treatment, which include conventional, targeted and genetically engineered biological drugs (GEBDs). When selecting a biological agent, a number of factors must be considered related to the disease, patient and therapy. Assessment of severity and activity, area of skin affected, frequency of relapses, pruritus and other symptoms, the presence of comorbidities, especially psoriatic arthritis (PsA), are important. The presence of comorbidities that may contribute to or interfere with the use of GEBD is the main factor determining personalised therapy. Personalised treatment implies maximum efficacy and minimum risk of side effects. In addition, it is possible to modify the course of the disease, inducing long-term remission and preventing the development of PsA, which is possible in case of timely prescription of GEBD. To date, several classes of GEBDs are available in the arsenal of dermatovenerologists, among which interleukin (IL) inhibitors have the highest efficacy and safety. The drug ixekizumab is a member of the IL-17 inhibitor group, a monoclonal antibody of the IgG4 class that binds to IL-17A with high affinity and specificity. The drug has shown high efficacy and reliable safety profile in the treatment of psoriasis and PsA within the framework of numerous clinical trials and studies of real clinical practice, including in patients with an aggravated comorbid background and with involvement of hard-to-treat localisations. The presented article presents key data of safety and efficacy studies of ixekizumab therapy, describes a clinical case of successful treatment of a patient with psoriasis and psoriatic onychodystrophy. Timely initiation of therapy helped to stop the progression of the disease and significantly improved the quality of life of the patient. Thus, the presented data confirm the advantages of ixekizumab in psoriasis treatment.

Screening of azo dye biosorption efficacy of free, immobilized, indigenous bacterial strains associated with azo dye contaminated river water—An in vitro study

AbstractAzo dye degradation utilizing microorganisms has acquired significance over the last decades, owing to its beneficial properties such as rapid degradation, economic feasibility, and eco‐friendly. In this work, azo dyes (Methyl red and methylene blue) degradation efficacy using indigenous bacterial strains Pseudomonas sp. and Bacillus sp. as free and immobilized cells were investigated under in vitro batch decolorization setup was carried. Most importantly, the bacterial cells of both strains were immobilized with sodium alginate and the immobilized cells were evaluated for dye decolorization efficacy under laboratory conditions. An eco‐toxic assessment of the degraded products was done using in vitro phytotoxicity tests and in silico analyses. Among the free and immobilized cells, maximum decolorization efficacy was observed in the Pseudomonas sp. immobilized cells which exhibited 74.5% decolorization efficacy, and the maximum decolorization efficacy of free cells was 63% of was observed. Ecotoxicity of the dye‐degraded products was screened by determination of phytotoxicity. Seedlings emergence of groundnut seeds exposed to degraded dye products revealed phytotoxicity. Results indicated that degraded dye products of methyl red derived from Pseudomonas sp. showed 93.0% seedling emergence, and methylene blue‐degraded products Pseudomonas sp. degraded dye products supported 92.0% seedling emergence, respectively. Bacterial cells immobilized with biocompatible polymers can be effectively utilized in wastewater treatment without affecting the ecological components. The findings highlight the value of this work in contributing to the domain of sustainable and eco‐friendly wastewater treatment technology.

Electrochemical studies, adsorption behavior, and spectroscopic analysis of vanadyl complex of bis(1-(pyridin-2-yl)ethylidene)malonohydrazide as efficient eco-friendly corrosion inhibitor for low carbon steel in 1M HCl

Corrosion is a destructive attack that can effect on a substance. One of the most important problems is corrosion losses, which can cause a loss of 10% of the metallic output every year. A novel VO+2 complex of N1, N3-bis(1-(pyridin-2-yl)ethylidene)malonohydrazide [(VO)2(L)(OH)2].H2O has been prepared and utilized as corrosion controller for Low carbon steel (LCS) in hydrochloric acid solution. Chemical (Weight loss (WL)), electrochemical (electrochemical impedance spectroscopy (EIS), and potentiodynamic polarization (PP)) are utilized to examine the effectiveness of prepared [(VO)2(L)(OH)2].H2O (VOL). The inhibition efficacy improved with increasing the VOL doses. The maximum efficacy of the investigated inhibitor is 96.1% at 21×10−6 M. However, at 21×10−6 M, the efficacy decreased from 96.1% to 84.4% when the temperature elevated from 298 to 318 K. The adsorption of VOL on the LCS surface was used to explain the inhibition. According to the values of ∆G°ads, which ranged from 25.8 to 21.5 kJ mol−1, the adsorption of the VOL on the LCS surface is physical adsorption. Analyzing the polarization curves of synthesized inhibitors revealed that they were mixed-type inhibitors. LCS was found to be surface inhibited when coated with a thin film of inhibitors, and surface morphology was assessed by different techniques such as scanning electron microscopy (SEM), energy dispersive X-ray (EDX), and atomic force microscope (AFM), and X-ray photoelectron spectroscopy (XPS). Density functional theory (DFT) was employed to explain the nature of the interface among VOL and LCS surfaces. It was found that all of these used tests agreed with each other.