Half-life Values Research Articles

Clinical pharmacokinetics and pharmacodynamics of ongericimab: A potential long-acting PCSK9 monoclonal antibody in healthy subjects and patients with hypercholesterolemia: Randomized, double-blind, placebo-controlled phase Ia and Ib/II studies.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) increases plasma low-density lipoprotein-cholesterol (LDL-C) by decreasing the expression of the LDL-receptor on hepatic cells. Ongericimab (JS002) is a novel PCSK9 monoclonal antibody that exhibits a long-acting LDL-C lowering effect by exclusively inhibiting PCSK9 in pre-clinical studies. Two randomized, double-blind, placebo-controlled trials were conducted to evaluate the safety, tolerability, efficacy, immunogenicity, pharmacokinetic, and pharmacodynamic profiles of ongericimab in healthy subjects and patients with hypercholesterolemia. Eighty-four healthy subjects in the phase Ia study received a single dose of placebo or ongericimab (15-450 mg). Ninety patients with hypercholesterolemia in the phase Ib/II study received placebo or ongericimab 150 mg Q2W, 300 mg Q4W, or 450 mg Q4W for 12 weeks. Ongericimab exhibited non-linear kinetics. The apparent clearance decreased as the dosage increased, with terminal elimination half-life (t1/2) values of 4.5-6.5 days. Overall, ongericimab was well tolerated in both studies. A single dose of ongericimab reduced LDL-C levels by 30%-73% in healthy subjects, and repeated doses of ongericimab reduced LDL-C levels by 67%-80% in patients with hypercholesterolemia. At the end of the dosing interval in the phase Ib/II study, over 70% of patients' LDL-C levels decreased by more than 50% from baseline. The results showed that ongericimab had a significant long-acting LDL-C lowering effect with good safety and potential for clinical application.

Study of Cluster Decays Including Those Leading to Doubly Magic Nucleus 298114 and Branching Ratios Relative to Alpha Decay

The study of superheavy nuclei (SHN) and their decay properties is one of the rapidly growing fields in nuclear physics. Using the CYE model, we have already studied the decay properties of the alpha decay, cluster decay, and spontaneous fission of the heavy and superheavy nuclei. In the present work, we will examine the effects by incorporating hexacontatetrapole (β6) parameter in the parent nucleus along with the quadrupole (β2), and hexadecapole (β4) deformations of the decaying parent nucleus emitting clusters 84Be and 126C. These deformations lower the half-life values, because they reduce the height and width of the potential barrier. Additionally, the creation of the doubly magic daughter 298114 from different decaying nuclei is computed. The calculated half-lives are compared with other models and are found to be in a good agreement. The branching ratios relative to the alpha-decay have also been calculated.

Kinetic study of the simultaneous removal of ibuprofen, carbamazepine, sulfamethoxazole, and diclofenac from water using biochar and activated carbon adsorption, and TiO2 photocatalysis

The growing number of pharmaceuticals released into the environment poses a threat not only to the aquatic environment but also to human health. This work introduces a novel approach for the simultaneous analysis of four pharmaceuticals—ibuprofen, carbamazepine, sulfamethoxazole, and diclofenac—each with distinct chemical structures. The study explores the kinetic behavior of these compounds during their removal from water, employing biochar and activated carbon as adsorbents, as well as titanium dioxide (TiO2) for photocatalytic degradation. This utilizes two distinct approaches incorporating adsorption mechanisms. The concentrations of pharmaceuticals were simultaneously measured using High Performance Liquid Chromatography with Diode Array Detection (HPLC-DAD). In addition to adsorption, photocatalysis with varying dosages of TiO2 was investigated as an alternative method for pharmaceutical removal. The HPLC- DAD analysis enabled the simultaneous monitoring of all four pharmaceuticals in a single analysis. The Langmuir-Hinshelwood model was applied to the photocatalysis data to assess reaction kinetics. The results demonstrate the efficacy of both adsorption methods in removing pharmaceutical contaminants from water. Integrating both adsorption and photocatalysis experiments in one manuscript allows for a comprehensive evaluation of these methods' individual strengths in water treatment applications, providing insights into their combined potential for addressing pharmaceutical contamination in water resources. The calculated removal efficiencies, Langmuir-Hinshelwood kinetics, half-life values, and equilibrium adsorption capacities provide a comprehensive understanding of the efficiency and mechanisms involved in the removal processes, emphasizing the importance of addressing pharmaceutical contamination in water treatment strategies.

A dose-adjusted, open-label, pilot study of the safety, tolerability, and pharmacokinetics of STC3141 in critically ill patients with sepsis.

Increased circulating histones correlate with sepsis severity and are a potential therapeutic target. Pre-clinical studies showed benefit with a histone-neutralizing polyanion molecule (STC3141). We aimed to investigate the safety, tolerability, and pharmacokinetics of STC3141 in critically ill patients with sepsis. We studied 26 patients with sepsis divided into four cohorts of one, five, ten, and ten subjects, respectively. We conducted a dose-adjusted, open-label study to determine the safety, tolerability, and pharmacokinetics of STC3141 administered as an IV infusion for up to 72 h, with rate adjusted to estimated creatinine clearance. Four steady-state concentrations were targeted. Twenty of the 26 subjects (77%) in the study experienced at least one adverse event (AE). The most frequently reported study drug-related AE was a mildly prolonged aPTT (four events). Only one AE (pulmonary hemorrhage) led to discontinuation of the drug. After excluding patients receiving renal replacement therapy (RRT) patients, clearance ranged from 3.3 to 4.2 L/h across cohorts and was essentially completely renal in nature. Half-life values ranged from 5 to 7 h. The mean (±SD) terminal half-life for non-RRT subjects and for whom it was possible to calculate was approximately 9 (±4.77) h but increased to 19 (±7.94) h for subjects on RRT. Overall, 18 (69.2%) patients completed the study to day eight in the ICU, and 22 (84.6%) survived to 28 days. STC3141 administration appeared to have an acceptable degree of safety and tolerability and expected pharmacokinetics. Cautious, larger randomized efficacy trials in sepsis appear justified.

Dissipation and persistence behaviour of fipronil and its metabolites in chilli fruits using GC-ECD, confirmed by GC-MS, under semi-arid conditions

Chilli, one of the most popular vegetables in the world is infested by many insect-pests and diseases. Fipronil, a phenylpyrazole class insecticide is used to manage insect-pests on chilli. The present study aimed to analyze the dissipation patterns and residual concentrations of the fipronil and its metabolites in chilli fruits during the Kharif season of 2020–21, in semi-arid environment. In the study, fipronil was applied to the plants twice, with a 10-day gap between treatments, using a 5 % suspension concentrate. The applications were undertaken using two separate concentrations i.e. the lower dosage of 40 g a.i. ha−1 and higher dosage of 80 g a.i. ha−1. There were four sets of data for each concentration. The chilli crop was systematically sampled at predetermined intervals after the application of the second spray. The procedure encompassed utilizing the modified QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) technique for extraction and purification, followed by analyzing the resulting residues using Gas Chromatography Electron Capture Detector. Gas Chromatography- Mass Spectrometry was subsequently conducted for the confirmation of the findings. The research revealed that the mean initial deposit of fipronil and its metabolites (desulfinyl, sulphide, and sulfone) at the authorized dosage was determined to be 0.574, 0.123, 0.031, and 0.180 mg kg−1, respectively. In contrast, when administered at twice the prescribed dosage, the mean first deposit was 1.204, 0.230, 0.067, and 0.382 mg kg−1. The half-life values of these residues exhibited a range of 1.2–4.1 days for both dosages. A prudent waiting duration was determined for the doses, leading to the conclusion that an average interval of 7 days is deemed safe for harvesting chilli peppers. The significance of this discovery is related to the maximum residue limits of 0.001 mg kg−1 for fipronil in green chilli, as established by the Food Safety and Standards Authority of India. This study provides significant insights into fipronil's persistence and proper management in chilli plant cultivation, emphasizing the importance of following prescribed dosages and designated waiting intervals to ensure the safety of food products.

Comparative Pharmacokinetics and Tissue Distribution of Hexahydrocurcumin Following Intraperitoneal vs Oral Administration in Mice Using LC-MS/MS.

A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to determine hexahydrocurcumin (HHC) levels in mouse plasma, brain, liver, and kidneys using a negative ion mode electrospray ionization (ESI) source. Demonstrating a lower limit of quantification (LLOQ) of 5 ng/mL, the method showed excellent linearity across a concentration range of 5-500 ng/mL in all tested matrices. Precision evaluations reported a coefficient of variation (CV%) of less than 13.19% for both intraday and interday measurements, while accuracy ranged from 95.13 to 105.07% across all quality control levels. HHC extraction recovery was consistently observed between 70.18 and 93.28%, with a CV% deviation of less than 15%. In the pharmacokinetic evaluation of HHC in mice following a single intraperitoneal (IP) or oral administration, a noncompartment analysis was utilized. After IP administration (40 mg/kg), the C max value was 47.90 times higher than that achieved via oral administration. Peak plasma concentrations were observed approximately 5 min post-IP and 15 min post-oral dosing. The observed half-lives after these administrations were approximately 1.52 and 2.17 h for IP and oral routes, respectively. Oral administration revealed a relative bioavailability of only 12.28% compared with the IP route. Furthermore, following IP administration, the half-life values in brain, liver, and kidney were not significantly different but more than the half-life value found in plasma. The liver and kidney exhibited the highest concentrations of HHC, while the brain showed the least, suggesting that the hydrophobic nature of HHC impedes its passage through the blood-brain barrier. This study is the first to provide detailed insights into the pharmacokinetics and tissue distribution characteristics of HHC following oral and IP administration in mice, setting the stage for further focus on HHC as a potential new drug candidate.

Half-life determination of 72Ga

Gallium-72 is an important Comprehensive Nuclear-Test-Ban Treaty relevant radionuclide that arouses significant interest. However, the reported half-lives of 72Ga are discrepant. In the current work, three solution samples of different concentrations were prepared and sequentially measured by a high-purity Germanium (HPGe) spectrometer. The count rates as a function of time of the 834.1 keV and 630.0 keV γ-lines were followed for the half-life determination. Through mass normalization, the datasets of three samples are combined and the statistical uncertainties are reduced. Half-life values were derived from datasets of each sample and mass normalization and corresponding complete uncertainty budgets are presented. The final half-life determined for 72Ga is 13.94 (2) h, showing a deviation of 1.12% from the last nuclear data sheets (NDS) recommended value. Comparing with the values of previous publications, the result from this work is smaller than most results and consistent with the latest value which has one large uncertainty. A recommended value of 14.07 (3) h is estimated using the power-moderated mean (PMM) method.

Measurement of the 117mSn, 125mTe, 135mBa and 195mPt half-lives for reactor dosimetry application

Nuclear isomers are investigated to perform precise epithermal neutron dosimetry. One key physical property for reactor dosimetry is the precise knowledge of the isomer half-life. In the list of potential candidates, the half-life values available in the literature or in the recommended database for reactor dosimetry for 117mSn, 125mTe, 135mBa and 195mPt show some discrepancy. New half-life measurements are presented in this work. Those isomers were produced by neutron activation at the JSI TRIGA Reactor from tin, tellurium, barium (all three of them enriched in their parent of interest) and natural platinum dosimeters. Precise half-lives measurements were performed at the MADERE platform using gamma and X-ray spectrometry. Special care has been taken on the uncertainty determinations.

Volatility Spillover Effect of NCDEX Spot and Futures Prices in Spices

This research is an attempt to assess the volatility in spot and futures prices in spices on NCDEX. Spot price and futures price Volatility is prominent indicators of the commodity futures market to protect the interest of beneficiaries and to hedge sharp price fluctuations in commodity markets. The study tested price patterns using data with 1777 observations for FY2015 to FY2022 daily spot and futures price series of near month contracts. VECM test and EGARCH were computed to examine spot and futures prices for three selected spices, namely jeera (cumin), turmeric and coriander. The results revealed that Turmeric and Coriander had significant bidirectional relationship and Jeera had significant unidirectional relationship between futures and spot market prices. Higher half-life (days) values of futures prices indicates more stability than spot prices of selected spices. Higher asymmetric effect value of spot market indicates higher volatility impacts because of noisy shocks than futures market.

Half-life of serum alpha-fetoprotein in prepubertal testicular yolk sac tumors: an index significantly associated with prognosis.

To evaluate the association between serum alpha-fetoprotein (AFP) half-life (HL) and prognosis in prepubertal children with elevated AFP values 3 to 4 weeks after surgery for testicular yolk sac tumors (YST). Prepubertal patients with testicular YST treated with radical orchiectomy between January 2016 and December 2022 were retrospectively reviewed. Negative outcomes were defined as relapse, metastasis or death. Univariate and multivariate logistic regression analyses were conducted to select risk factors for negative outcomes. A total of 42 patients were eventually enrolled into the study. Patients were divided into non-negative and negative outcomes groups, consisting of 35 and 7 patients, respectively. Thirty-five patients were stage I, two cases were stage II, and five cases were stage IV, according to the Children's Oncology Group staging system. The overall survival (OS) rate was 100%. Average AFP values significantly decreased after resection (P < 0.001). A significant positive correlation was shown between pre- and postoperative AFP values (r = 0.60, P < 0.001). Long AFP HL was considered as an independent risk factor for negative outcomes in YST patients underwent radical orchiectomy (P = 0.04). The cut-off value for AFP HL was 5.78 days, regardless of age division. Testicular YST is a relatively rare disease in children with an OS of 100%, and salvage chemotherapy is effective even in grade IV patients. The postoperative AFP HL was significantly associated with prognosis in prepubertal patients with testicular YST. The cut-off value for AFP HL is 5.78 days regardless of the effect of physiological AFP elevation.

Engineering of Methionine Adenosyltransferase toward Mitigated Product Inhibition for Efficient Production of S-Adenosylmethionine.

S-Adenosylmethionine (SAM) is a crucial metabolic intermediate playing irreplaceable roles in organismal activities. However, the synthesis of SAM by methionine adenosyltransferase (MAT) is hindered by low conversion due to severe product inhibition. Herein structure-guided semirational engineering was conducted on MAT from Escherichia coli (EcMAT) to mitigate the product inhibitory effect. Compared with the wild-type EcMAT, the best variant E56Q/Q105R exhibited an 8.13-fold increase in half maximal inhibitory concentration and a 4.46-fold increase in conversion (150 mM ATP and l-methionine), leading to a SAM titer of 47.02 g/L. Another variant, E56N/Q105R, showed superior thermostability with an impressive 85.30-fold increase in half-life (50 °C) value. Furthermore, molecular dynamics (MD) simulation results demonstrate that the alleviation in product inhibitory effect could be attributed to facilitated product release. This study offers molecular insights into the mitigated product inhibition, and provides valuable guidance for engineering MAT toward enhanced catalytic performance.

Toxicokinetics of α- and β-amanitin in mice following single and combined administrations: Simulating in vivo amatoxins processes in clinical cases

α-Amanitin and β-amanitin, two of the most toxic amatoxin compounds, typically coexist in the majority of Amanita mushrooms. The aim of this study was to use a newly developed ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) method to determine the toxicokinetics and tissue distribution of α- and β-amanitin following single or combined oral (po) administration in mice. α-Amanitin and β-amanitin administered at 2 or 10 mg/kg doses showed similar toxicokinetic profiles, except for peak concentration (Cmax). The elimination half-life (t1/2) values of α-amanitin and β-amanitin in mice were 2.4–2.8 h and 2.5−2.7 h, respectively. Both α- and β-amanitin were rapidly absorbed into the body, with times to reach peak concentration (Tmax) between 1.0 and 1.5 h. Following single oral administration at 10 mg/kg, the Cmax was significantly lower for α-amanitin (91.1 μg/L) than for β-amanitin (143.1 μg/L) (p < 0.05). The toxicokinetic parameters of α-amanitin, such as t1/2, mean residence time (MRT), and volume of distribution (Vz/F) and of β-amanitin, such as Vz/F, were significantly different (p < 0.05) when combined administration was compared to single administration. Tissues collected at 24 h after po administration revealed decreasing tissue distributions for α- and β-amanitin of intestine > stomach > kidney > lung > spleen > liver > heart. The substantial distribution of toxins in the kidney corresponds to the known target organs of amatoxin poisoning. The content in the stomach, liver, and kidney was significantly higher for of β-amanitin than for α-amanitin at 24 h following oral administration of a 10 mg/kg dose. No significant difference was detected in the tissue distribution of either amatoxin following single or combined administration. After po administration, both amatoxins were primarily excreted through the feces. Our data suggest the possibility of differences in the toxicokinetics in patients poisoned by mushrooms containing both α- and β-amanitin than containing a single amatoxin. Continuous monitoring of toxin concentrations in patients’ blood and urine samples is necessary in clinical practice.

Paclobutrazol persistence dynamics in mango (Mangifera indica) orchard soil using HPLC and LC-MS/MS analysis

Paclobutrazol, a plant growth regulator, is used commercially in soil application to counter the alternate bearing habit of mango (Mangifera indica L.) all over the country. The experiments were conducted during 2020–21 and 2021–22 at ICAR-Central Institute for Subtropical Horticulture, Lucknow, Uttar Pradesh to study the persistence of paclobutrazol in soil and its subsequent uptake in mango fruits using HPLC and validated by LC-MS/MS after its application to tree basin soil of mango cv. Dasheri @2, 4, 6, 8 and 10 g a.i./tree. The residues of paclobutrazol dissipated in soil from its initial values of 10.33, 17.25, 25.71, 50.80, and 62.36 µg/g soil at 0 days to 0.14, 0.30, 0.47, 1.32 and 2.38 µg/g soil after 300 days of application. The dissipation rate in soil followed first-order kinetics with half-life values ranging between 57.75 and 77.00 days. Residues of paclobutrazol were not detected in fully mature fruits harvested after 85 days of fruit set. LC-MS/MS analysis confirmed that the sample peaks corresponded to paclobutrazol residues in mango fruit and soil. Thus, HPLC and LC-MS/MS analysis clearly showed that the paclobutrazol persisted in the soil for longer, but the mature fruits harvested from treated trees were free from its residue even at higher doses and safe for consumption. The response of paclobutrazol to the quality of fruits in terms of phenolic content was also assessed. The paclobutrazol was more responsive in altering phenolic acid composition than the control.

Pharmacokinetics of oxytetracycline in hybrid catfish (Clarias macrocephalus x C. gariepinus) after intravascular and oral administrations.

Over the past decade, catfish farming has increased in Southeast Asia. However, there has been no existing for pharmacokinetic data in the hybrid catfish (Clarias macrocephalus x C. gariepinus). This study was designed to evaluate the pharmacokinetic characteristics of oxytetracycline (OTC) in the hybrid catfish, following single intravascular (IV) or oral (PO) administration at a single dosage of 50 mg/kg body weight (BW). In total, 140 catfish (each about 100-120 g BW) were divided into two groups (n = 70). Blood samples (0.6-0.8 mL) were collected from ventral caudal vein at pre-assigned times up to 144 h (sparse samples design). OTC plasma concentrations were analyzed using high-performance liquid chromatography-photodiode array detector. The pharmacokinetic parameter of OTC was evaluated using a non-compartment model. OTC plasma concentrations were detectable for up to 144 and 120 h after IV and PO, respectively. The elimination half-life value of OTC was long with slow clearance after IV administration in hybrid catfish. The average maximum concentration value of OTC was 2.72 µg/mL with a time at the maximum concentration of 8 h. The absolute PO bioavailability was low (2.47%). These results showed that PO administration of OTC at a dosage of 50 mg/kg BW was unlikely to be effective for clinical use in catfish. The pharmacodynamic properties and clinical efficacy of OTC after multiple medicated feed are warranted.

Edible insects: Understanding benzo(a)pyrene toxicokinetics in yellow mealworms for safe and sustainable consumption

The global interest in edible insects as sustainable protein sources raises concerns about the bioaccumulation of contaminants, including polycyclic aromatic hydrocarbons (PAHs), to problematic levels. Understanding the accumulation dynamics of PAHs in edible insects is highly relevant due to the widespread sources and toxicological profiles; however, the bioaccumulative potential of PAHs in edible insects is unexplored. This study examined the uptake and elimination dynamics of benzo(a)pyrene (B(a)P), a representative and carcinogenic PAH, in yellow mealworm larvae (YMW, Tenebrio molitor). Larvae were exposed to feeding substrate with varying B(a)P concentrations (0.03, 0.3, and 3 mg kg−1), and uptake (21 days in B(a)P-contaminated substrate) and elimination (21 days in B(a)P-free substrate) kinetics were subsequently assessed. The results showed that YMW can eliminate B(a)P, revealing dose-dependent B(a)P bioaccumulation in these insects. Larvae fed on a substrate with 0.03 mg kg−1 accumulated B(a)P over 21 days, presenting values of 0.049 (Standard deviation - 0.011) mg kg−1 and a kinetic-based (BAFkinetic) of 1.93 g substrate g organism−1, exceeding the EU regulatory limits for food. However, with a B(a)P half-life (DT50) of 4.19 days in the larvae, an EU legislation safety criterion was met after a 13-day depuration period in clean substrate. Larvae exposed to substrates with 0.3 and 3 mg kg−1 showed B(a)P accumulation, with BAFkinetic values of 3.27 and 2.09 g substrate g organism−1, respectively, not meeting the current legal standards for food consumption at the end of the exposure to B(a)P. Although the B(a)P half-life values after 35 days were 4.30 and 10.22 days (DT50s), the larvae retained B(a)P levels exceeding permitted food safety limits. These findings highlight a significant oversight in regulating PAHs in animal feed and the need for comprehensive safety evaluations of PAH hazards in edible insects for improved PAH feeding guidelines.

Cations impact the biodegradation of iodosulfuron-methyl herbicidal ionic liquids by fungi

ABSTRACT In the framework of this study, six fungal isolates which demonstrated a high capability for biodegrading iodosulphuron-methyl sodium as well as herbicidal ionic liquids based on this herbicide were isolated from different soil samples. The isolates were identified based on the ITS region, whereas biodegradation residues were determined based on LC-MS/MS. Depending on the isolate, the half-lives values of the biodegraded herbicide or herbicidal ionic liquid ranged significantly from just 1.25 days to more than 40 days. The research findings unveiled that the structure of cations is a central limiting factor affecting fungal growth and herbicide transformation in case of ionic liquids. The length of the alkyl chain has been identified as the primary driver of herbicide toxicity, emphasizing the importance of structural factors in herbicide design. In cases when dodecyl(2-hydroxyethyl)dimethyl cation was used, its biodegradation ranged from 0 to approx. 20% and the biodegradability of the iodosulfuron-methyl was notably limited for the majority of the studied isolates. This knowledge provides guidance for development and selection of herbicides with reduced environmental impact. This study highlights the ecological importance of soil fungi, their potential role in herbicide biodegradation, the influence of cations on fungal growth and herbicide transformation, and the structural factors governing herbicide toxicity. Further research in these areas may lead to more efficient and environmentally friendly approaches to herbicide management.

Celastrol-loaded polymeric mixed micelles shows improved antitumor efficacy in 4 T1 bearing xenograft mouse model through spatial targeting

In this study, we have proposed a novel approach that combines hyaluronic acid (HA), folic acid (FA), and celastrol (CLS) within a polymeric micelle system (CLS-HF/MLs), offering a dual-action strategy against breast cancer. Polymeric mixed micelles were prepared through the thin-film hydration method, and comprehensive quality control parameters were established, encompassing particle size, polydispersity index, zeta potential, surface morphology, encapsulation efficiency, drug content, in vitro drug release, and storage stability assessment. The average particle size of CLS-HF/MLs micelles was found to be 120 nm and their drug loading and encapsulation efficiencies were 15.9 % and 89.52 %, respectively. The in vitro release data showed that the CLS-HF/MLs targeted mixed micelles displayed a prolonged release profile compared to the free drug. Additionally, the stability of the developed polymeric mixed micelles was maintained for up to 8 weeks of storage in terms of particle size and drug content. Furthermore, both flow cytometry and confocal laser scanning microscopy studies indicated a significant enhancement in the cellular uptake efficiency and cytotoxicity of CLS-HF/MLs mixed micelles against MCF-7 cell line. In terms of pharmacokinetic analysis, the half-life and AUC values of CLS-HF/MLs mixed micelles were found to be approximately 4.71- and 7.36-folds higher than the values of free drug (CLS), respectively. The CLS-HF/MLs micelles exhibited remarkable antitumor efficacy (almost complete ablation of the 4 T1-cell bearing tumor xenografts mouse model) due to the dual receptor (CD44 and folate) targeting effects with minimal side effects. When considering the cumulative findings of our present research, it becomes evident that mixed micelles designed for chemotherapy offer a promising and potentially effective therapeutic avenue for the treatment of breast cancer

Degradation and inhibition kinetics of phenanthrene by Alcaligenes ammonioxydans, [VITRPS2] strain isolated from petroleum-contaminated soil

Phenanthrene, a common three-ring polyaromatic hydrocarbon [PAH], originates from sources like grilled meals, tobacco, crude oil, coal tar, and automobile exhaust. Recognized as a hazardous PAH, it is often targeted for bioremediation due to its sustainability and potential for full mineralization. In this study, we focus on biodegrading phenanthrene using the strain Alcaligenes ammonioxydans [VITRPS2], isolated from petroleum-contaminated soil. At 5 mg/ml, degradation occurred at a rate constant of 0.0181/day, with half-life values of 2.7 and 4.49 according to first and second-order kinetics, respectively. Employing a one-factor-at-a-time [OFAT] approach, we optimized biodegradation conditions within Luria–Bertani [LB] media. Under optimal conditions—pH 8.0, 8% inoculum concentration, and 37 °C incubation over seven days—the strain achieved maximal growth with phenanthrene as the sole carbon source. It exhibited a degradation efficiency of up to 72% for phenanthrene under these conditions. Gas chromatography-mass spectrometry [GC–MS] analysis revealed principal metabolites of the breakdown pathway, including salicylic acid, catechol, and various phthalic acid derivatives. This underscores the strain's potential for remediating environments polluted by PAH metabolites, showcasing its remarkable capability for complete phenanthrene degradation.Graphical abstract

Dissipation kinetics, dietary risk assessment and decontamination studies of tolfenpyrad in okra

QuEChERS method with liquid chromatography-mass spectrometry (LC-MS/MS) technique was employed for the estimation of tolfenpyrad residues in okra crop. The method was validated in terms of linearity, matrix effect, limit of quantification (LOQ), limit of detection, recovery, repeatability and reproducibility as per SANTE (2021) guidelines. After two applications of tolfenpyrad @150 (X), 187.5 (1.25X), 300 g a.i. ha−1 (2X), the mean initial residues were found to be 0.57, 0.78, and 1.21 mg kg −1. The residues reached below limit of quantification of 0.01 mg kg−1 after 10th, 15th, and 20th day at all the three doses, respectively. Dissipation kinetics of tolfenpyrad in okra was calculated to follow first order kinetics with half-life (T1/2) values of 2.10, 2.16, and 2.24 days at X, 1.25X and 2X dosages, respectively. Risk assessment in terms of hazard quotient (HQ) revealed that the application of tolfenpyrad was safe for safe consumption. Decontamination processes involved tap water wash, soaking in 2% salt solution, soaking in 2% salt solution along with boiling, soaking in 0.1% sodium bicarbonate solution, soaking in 0.01% potassium permanganate solution, boiling and frying. Frying followed by soaking in 2 per cent salt solution along with boiling proved to be highly effective in reducing tolfenpyrad residues by 80–85 and 76–79 per cent, respectively at all the three treatments.

The multiple enhancements of deep eutectic solvent on cellulase significantly improve the saccharification efficiency of lignocellulosic biomass

The introduction of specific choline chloride (ChCl)- and betaine (Bet)-based deep eutectic solvents (DESs) into the conventional acetic acid–sodium acetate solution led to a significant increase in cellulase activity and stability. In particular, a higher enhancement in β-glucosidase activity was obtained, which plays a key role in improving cellulase function. The DESs prolonged the half-life of cellulase. The addition of 10 % (v/v) ChCl/1,3-propanediol (1:2) and 5 % (v/v) Bet/glycerol (1:2) resulted in the most significant improvement, with the half-life of cellulase reaching three times the initial half-life value. The above both DESs allowed the cellulase to maintain an excellent level of activity over time, even after 72 h. The DESs tightened the structure of the enzyme by changing its secondary structure, which had a stabilizing effect on the overall conformation. The density functional theory calculations of DESs revealed that the DES with a more stable structure more effectively protected the active conformation. The molecular dynamics simulation on β-glucosidase indicated that the hydrogen bond donor end of the DES primarily formed hydrogen bonds with the enzyme, which induced a spatially compact conformation by increasing the α-helix content while reducing the β-sheet content. It also restricted the movement of amino acids, particularly stabilizing the active site, and increased the hydrophilic region, thereby enhancing enzyme activity and stability. In addition, the DES formed a protective layer that prevented the unproductive adsorption of lignin on the enzymes during the hydrolysis of lignocellulosic feedstocks. These multiple improvements provided by DESs significantly increased the enzymatic saccharification efficiency of corn stover and poplar.