Degradation Products Research Articles

Exogenous allyl isothiocyanate mitigates the drought stress by regulating the stomatal characteristic, antioxidant capacity, and glucosinolate metabolism in pakchoi

Drought is a global issue that has increasingly garnered worldwide attention. Glucosinolates (GSLs) are significant sulfur-containing compounds in cruciferous plants such as pakchoi (Brassica rapa L. ssp. chinensis), and their primary biological functions are exerted through their hydrolysis products. Allyl isothiocyanate (AITC), which is one of the degradation products of GSL, plays a crucial role in plants' response to environmental stresses. To date, the drought-resistant mechanism of AITC has not been fully explored. This study investigated the effects of spraying different concentrations of AITC solutions (1 mM and 10 mM) on the growth parameters, stomatal characteristics, antioxidant indices, and glucosinolate metabolism of pakchoi under drought stress, compared to a control group treated with distilled water. The results showed that under drought stress, AITC treatment significantly improved water retention and restored their growth by promoting stomatal closure and improving photosynthetic capacity in pakchoi; mitigated oxidative stress damage and augmenting the plant's water absorption by increasing the activities of antioxidant enzymes and the concentrations of osmoregulatory substances in pakchoi; the application of AITC restored the glucosinolate metabolism in pakchoi, inhibiting the downregulation of genes associated with GSL synthesis and the upregulation of genes related to degradation that is induced by drought stress, thereby maintaining the balance between GSLs and ITCs. In conclusion, AITC application alleviated the inhibition of pakchoi growth under drought stress by fostering stomatal closure, bolstering antioxidant defenses, and modulating glucosinolate metabolism.

Visible-light-driven photocatalytic degradation of HCBD using BP/TiO2/CN: Enhanced mechanisms, ecological risks, and management insights

BPNS have attracted significant attention due to their outstanding photocatalytic performance. However, their practical application is often limited by rapid charge recombination. This study introduces a BP/TiO2/CN ternary heterojunction (P-N) that is constructed by sequentially depositing semiconductor materials with varying band gaps onto a single substrate. The composite consisting of 5 mg BP, 30 %TiO2, and 10 %CN (BTC-1) exhibited remarkable pollutant degradation under visible light, achieving a 95 % removal rate for HCBD (50 ppb, 200 mL) within 150 min. This enhanced performance can be attributed to an increase in adsorption sites, improved light absorption, and the effective separation of electron-hole pairs. The degradation mechanism indicates that the removal of HCBD involves de-chlorination and radical attack on its CC bonds. Electrons from the conduction band of BPNS migrate to CN and subsequently to TiO2, with CN acting as a bridging layer. Simultaneously, holes from the valence band of TiO2 transfer to CN and ultimately reach BPNS, thereby enhancing charge separation. The proposed photocatalytic mechanism suggests that ·OH and ·O2−play crucial roles in HCBD degradation, with ·OH being the primary active species. Using TEST software (QSAR method), it was determined that the intermediate degradation products of HCBD are primarily small molecules and ions, which exhibit significantly reduced toxicity and lower ecological risks. This study highlights the practical application potential of BTC-1 in HCBD removal, emphasizing economic benefits and providing insights into the synergistic effects of non-metallic catalysts. Furthermore, it offers a deeper understanding of the mechanisms underlying HCBD degradation, along with new perspectives on toxicity assessment and environmental management of HCBD.

Quantum Simulations of Radiation Damage in a Molecular Polyethylene Analog.

An atomic-level understanding of radiation-induced damage in simple polymers like polyethylene is essential for determining how these chemical changes can alter the physical and mechanical properties of important technological materials such as plastics. Ensembles of quantum simulations of radiation damage in a polyethylene analog are performed using the Density Functional Tight Binding method to help bind its radiolysis and subsequent degradation as a function of radiation dose. Chemical degradation products are categorized with a graph theory approach, and occurrence rates of unsaturated carbon bond formation, crosslinking, cycle formation, chain scission reactions, and out-gassing products are computed. Statistical correlations between product pairs show significant correlations between chain scission reactions, unsaturated carbon bond formation, and out-gassing products, though these correlations decrease with increasing atom recoil energy. The results present relatively simple chemical descriptors as possible indications of network rearrangements in the middle range of excitation energies. Ultimately, the work provides a computational framework for determining the coupling between nonequilibrium chemistry in polymers and potential changes to macro-scale properties that can aid in the interpretation of future radiation damage experiments on plasticmaterials.

Biodegradation and high-value utilization of waste cooking oil: Strategies and mechanisms for producing lipopeptide biosurfactants using Bacillus subtilis YZQ-2

This study explored the strategies and mechanisms of Bacillus subtilis YZQ-2 in producing lipopeptide biosurfactants using waste cooking oil (WCO) as a raw material. The optimal conditions achieved a WCO utilization rate of 75.88 % and a biosurfactant yield of 0.30 g/L at pH 6.0, 30°C, with 20 g/L WCO and 5 g/L yeast extract. GC-MS analysis of degradation products at different intervals elucidated the mechanism of WCO degradation. After 72 hours of fermentation, a reduction in linoleic and palmitic acid levels indicated the completion of lipid hydrolysis and the continuation of β-oxidation. The biosurfactants, identified as lipopeptides (surfactin and fengycin), exhibited stability in alkaline environments (pH 7.0–11.0) and high-salt concentration (5–45 g/L). Genomic and transcriptomic analyses of Bacillus subtilis YZQ-2 revealed genes associated with biosurfactant production, which were upregulated in the presence of WCO. The differential expression values (log2 fold change) were SrfAA 3.30, SrfAB 3.31, SrfAC 3.63, FenA 2.42, FenB 2.55, FenC 1.99, FenD 2.03 and FenE 2.29, respectively. The proposed biosynthesis pathway of lipopeptides begins with the hydrolysis of WCO by lipase into glycerol and fatty acids. The glycerol is then transformed into pyruvate through glycolysis, entering the Tricarboxylic Acid cycle. Additionally, pyruvate contributes to synthesizing amino acids and branched-chain fatty acids, which serve as precursors for lipopeptide synthesis. These findings underscore the potential of WCO as a sustainable feedstock for biosurfactant production.

Pea Pod–Derived Biochar–Zeolitic Imidazolate Framework Composite for the Photocatalytic Degradation of Two Organic Dyes Crystal Violet and Victoria Blue

ABSTRACTThe rapid increase of water pollution globally is a vital environmental concern that requires the immediate attention of researchers to find new innovative ways to remove unwanted environmental pollutants from our water sources. With the advances in the field of sustainable engineering, there is a high demand for the effective utilization of biomass resources for the removal of aqueous environmental contaminants. Biochar is carbon carbon‐enriched substance obtained by biomass pyrolysis; it is inexpensive and has received wide attention in the field of wastewater treatment. Herein, we describe the synthesis of pea pod (PO) biochar‐reinforced zeolitic imidazolate framework (ZIF‐8) nanocomposite (PO@ZIF‐8) through the in situ precipitation of ZIF‐8 onto the biochar surface. The crystal growth, morphology, chemical composition, and optical characteristics of fabricated PO@ZIF‐8 nanocomposite were scrutinized through PXRD, SEM, TEM, UV‐DRS, PL, and XPS analysis. The dodecahedral‐shaped PO@ZIF‐8 particles have an average size between 140 and 160 nm. The biochar‐reinforced ZIF‐8 nanocomposite showed significantly higher photocatalytic activity than the pure ZIF‐8 for the degradation of two commonly found organic dyes crystal violet (CV) and Victoria Blue (VB) in the presence of direct sunlight irradiation. The PO@ZIF‐8 nanocomposite showed the highest degradation efficiency of ~87% and ~80% within 50 min of irradiation time at a catalyst dosage of 20 mg for 30 ppm CV and VB dye solutions at pH 8. First‐order kinetics were obeyed during the photodegradation with 0.041 and 0.030 min−1 as the constant of degradation for the removal of CV and VB. The radical scavenger experiment and the photoluminescence analysis confirm the active participation of ·OH radical in the degradation of both dyes. LC–MS and TOC analysis was also performed to determine the degradation products and for evaluation of the degradation progress. Moreover, the synthesized PO@ZIF‐8 composite also exhibit good stability till the fourth cycle with high degradation efficiency thus making it a good choice of catalyst in the field of environmental decontamination.

Method Development and Validation of Luliconazole Bulk Drug Using Reverse Phase - HPLC Technique

Objective: To develop and validate the RP- HPLC method for determining Luliconazole in bulk and pharmaceutical formulations. Methods: Following the International Conference on Harmonization (ICH) guidelines, a sensitive, accurate, and specific reversed-phase HPLC technique was created and validated for the detection of Luliconazole. Using high-performance liquid chromatography, this drug was examined. A better separation of the drug was achieved by using Agilent Eclipse XDB C (4.6mm x 250mm, 5µm) with a mobile phase consisting of a mixture of Acetonitrile and Buffer in HPLC water. The ratio of 30:70 v/v (Formic acid and Acetonitrile) at a flow rate of 1.0 ml/ min and the detection was at the wavelength 295 nm using a Photodiode Arrays Detector. The planned method was able to produce good quality separation of the drug and its degradation products with sharp peaks. Findings: Luliconazole had a retention time of 2.38 ± 0.127 minutes. The technique was linear in the range of 10-100 µg/ml, with a correlation (r2) of 0.9995 and a run duration of 4 minutes. The method limit of detection (LOD) and limit of quantification (LOQ) were set at 0.1 and 1 g/ml, respectively. The method accuracy and system precision were estimated, and the findings were calculated as percentage RSD values, which were found to be limitations. Luliconazole recovery was 100% confirming the method's efficiency. Novelty: The presented approach was innovative and successfully fulfilled all validation requirements, including linearity, robustness, accuracy, reduced retention, and run time. This suggests that the method is appropriate for identifying the stability of luliconazole in bulk and pharmaceutical formulations. Keywords: RP-HPLC, Transferosome, ICH guidelines, Validation, Luliconazole

Efficient Adsorption and Degradation of Tetracycline Hydrochloride Using Metal-Organic Framework-Derived Cobalt-Based Catalysts and Mechanism Insight.

High-performance Co-based catalysts were derived by pyrolysis using synthesized MOFs as self-sacrificial templates. Various catalytic systems were constructed by peroxymonosulfate (PMS) to degrade tetracycline hydrochloride (TC). Adsorption-degradation efficiencies, cycle performance, dynamics, and the adsorption catalytic mechanism of various catalytic systems for TC were studied. The effects of different synthetic solvents, pyrolysis temperatures, and single/bimetallic element compositions on degradation efficiency were innovatively compared. The optimal catalyst and PMS dosage for the experiment were determined to be 10 mg and 0.1 mL, respectively. The results indicated that all catalytic systems could efficiently degrade TC and have a high acid-base resistance. The catalyst activity was significantly influenced by the pyrolysis temperature. The optimum pyrolysis temperatures for Zn@Co-N-C-T, CH3OH@Co-N-C-T, and H2O@Co-N-C-T were 1000, 900 and 900 °C, respectively. More abundant pore structures and active sites were generated in Zn@Co-N-C-1000, exhibiting an excellent TC degradation efficiency and adsorption capacity, achieving 94.73% and 167.564 mg/g, respectively. Meanwhile, the total organic carbon (TOC) of TC (50 mL, 50 mg/L) achieved a removal rate (TOC/TOC0) of 50.28%. Zn@Co-N-C-1000/PMS maintained over 83.27% TC degradation after five cycles. The adsorption mechanism of the catalyst for TC was investigated through the analysis of adsorption kinetics and isotherm models. The quenching test and EPR results indicated that TC was primarily degraded through the nonradical pathway. The efficient degradation of TC is attributed to the rapid electron transfer processes occurring at the two-phase interface and the redox cycling of Co0/Co2+/Co3+. Finally, LC-MS was used to analyze the intermediate products of TC degradation in the Zn@Co-N-C-1000/PMS system, and two degradation pathways were proposed.

Influence of UV-B and culinary treatment on vitamin D2 and agaritine in button mushrooms

This study investigated the effects of different culinary treatments on the levels of vitamin D2 and agaritine in irradiated white button mushrooms. In addition, the intake of this vitamin via mushroom dishes was evaluated. In fresh irradiated white button mushrooms, the vitamin D2 content was 21.5 ± 2.4 µg/100 g fresh weight, 42 % of which was in the cap skin. The highest losses of vitamin D2 (63 %) were found in samples boiled in acidic water. In contrast, the lowest losses were found in samples boiled in non-acidified water. In the baking and frying experiments, vitamin D2 retention depended more on the cooking time than on the temperature. This resulted in high-heat frying being the second-best treatment for retaining vitamin D2 content in the samples. In the case of agaritine, no effect of UV treatment on its content was observed, and cooking treatment reduced its consumption. At the same time, the formation of toxic degradation products was not observed. The Recommended Daily Intake (RDI) of vitamin D can be achieved by consuming about 75–190 g of cooked, irradiated white button mushrooms, which can thus be an important dietary source of this vitamin.

MIL-125-PDI/ZnIn2S4 Inorganic-Organic S-Scheme Heterojunction With Hierarchical Hollow Nanodisc Structure for Efficient Hydrogen Evolution from Antibiotic Wastewater Remediation.

Efficient photocatalytic production of H2 from wastewater is expected to address environmental pollution and energy crises effectively. However, the rapid recombination of photoinduced carriers results in low photoconversion efficiency. At present, inorganic-organic S-scheme heterojunction have become a prominent and promising technology. In this study, an organic ligand modified MIL-125-PDI/ZnIn2S4 (ZIS) inorganic-organic S-scheme heterojunction catalyst is designed. ZIS nanosheets are grown on the disc-shaped MIL-125-PDI surface to form a distinctive hollow nanodiscs with hierarchical structure, giving the material an abundance of surface active sites, an optimized electronic structure, and a spatially separated redox surface. Consequently, the optimal 100MIL-125-PDI250/ZIS exhibited high photocatalytic HER of 508.99 µmol g-1 h-1 in Tetracycline hydrochloride (TC-HCl) solution. Meanwhile, the catalyst achieved complete TC-HCl removal and mineralization rate of 66.62% in 4h. Experimental and theoretical calculations corroborate that the staggered band alignment and work function difference between MIL-125-PDI and ZIS induce the formation of a built-in electric field, thus regulating the charge transfer routes and consequently enhancing charge separation efficiency. The possible photocatalytic mechanism is analyzed using liquid chromatography-mass spectrometry (LC-MS), and the toxicities of the degradation products are also evaluated. This work presents a green dual-function strategy for H2 production and antibiotic wastewater recycling.

Laccase immobilized on amino modified magnetic biochar as a recyclable biocatalyst for efficient degradation of trichloroethylene

Bioremediation of trichloroethylene (TCE) contaminated groundwater has recently attracted considerable attention. In this study, laccase was immobilized on amino modified magnetic pine biochar (MBC-NH2) by adsorption-crosslinking-covalent binding method, and its application in the degradation of TCE was evaluated. MBC-NH2 was obtained from pine sawdust by calcination, magnetic modification and amino modification. MBC-NH2 had high specific surface area (71.3 m2/g), rich surface functional groups and good magnetism. Under the conditions of 25 °C, pH = 4, glutaraldehyde (GA) concentration of 7 %, crosslinking time of 1 h, laccase concentration of 0.75 mg/mL, and immobilization time of 7 h, the loading capacity of laccase on MBC-NH2 carrier was as high as 782 mg/g. Compared with free laccase, immobilized laccase showed higher pH stability and thermal stability, and its activity remained 48.5 % after being reused for 10 times, and 80.8 % after being stored at 4 °C for 30 days. The immobilized laccase exhibited a good degradation effect on TCE. At 25 °C, pH = 4, immobilized laccase concentration of 0.35 g/L, and initial TCE concentration of 10 mg/L, the degradation efficiency of TCE by immobilized laccase was as high as 92.1 % within 48 h. In addition, the degradation products of TCE were analyzed, and the results showed that immobilized laccase could degrade TCE into non-toxic products through epoxidation, hydroxylation, and dechlorination. The immobilized laccase biocatalyst prepared in this study can achieve efficient degradation of TCE, which provides a feasible solution for chlorinated pollution of water resources. These research results are of great significance for the synthesis of biocatalysts for the efficient degradation of chlorinated hydrocarbons.

Efficient degradation of the polysaccharide extracted from Enteromorpha prolifera by using a novel polysaccharide lyase family 28 enzyme with high activity

The polysaccharides originated from Enteromorpha species exhibited versatile physiological activities and great potential in food and medicine industries. The oligosaccharides, which prepared from polysaccharide by enzymatic hydrolysis, retained the excellent activity as polysaccharide, and then revealed better solubility, bioavailability and effectiveness. However, there are few reports on Enteromorpha polysaccharide (EP)-degrading enzymes for efficient degradation of EP and high-valued utilization of Enteromorpha biomass. Herein, a novel EP-degrading enzyme, EPD1, was identified and heterologously expressed. It could efficiently hydrolyze the EP with high activity (985.755 U/mg) and exhibited optimal activity at 50 °C and a pH of 10.0. The Km value of EPD1 was 7.5512 mg·mL−1 and the Vmax value was 4.9109 μmol·min−1·mL−1. Furthermore, EPD1 demonstrated cold adaptation as evidenced by minimal activity loss following incubation at temperatures below 30 °C for 1 h. HPLC and ESI-MS analysis revealed that EPD1 could produce disaccharides, trisaccharides and tetrasaccharides as the final degradation products from EPs. In conclusion, a novel EP-degrading enzyme with high activity and excellent performance was identified and it can expand the database of EP-degrading enzymes and provide the possibility to make full use of EPs.

Activation of persulfate by MOF-derived MnFeOx to efficiently degrade sulfadiazine: Synergistic effects from free radicals and singlet oxygen

In this study, a facile hydrothermal approach was used to synthesize the MOFs materials [Mn-doped MIL-101(Fe)]. These materials were subsequently subjected to high temperature annealing process via calcination to generate the MOFs derivatives (MnFeOx). The synthesized materials were utilized for the removal of sulfadiazine (SDZ) removal through activated peroxymonosulfate (PMS). At the optimum Mn doping, the removal ratio of SDZ could reach 98.9 % (at natural pH) within 20 min. In addition, the study investigated the influence of PMS dosage, catalyst dosage, initial pH, various inorganic anions, and humic acid (HA) on the degradation of SDZ. The activation processes of both free and non-free radicals in the MnFeOx/PMS system were examined by free radical quenching experiments and electron paramagnetic resonance (EPR) techniques. The analysis of the degradation products of SDZ was conducted by using high performance liquid chromatography-mass spectrometry (HPLC-MS), and the breakdown pathways of SDZ in the MnFeOx/PMS system were proposed.

Green-synthesized BiFeO3 nanoparticles for efficient photocatalytic degradation of organic dyes, antibiotic and catalytic reduction of 4-nitrophenol

Green-synthesized nanoparticles have recently emerged as promising catalysts for the removal of toxic dyes from water bodies. In this article, Bismuth ferrite nanoparticles were synthesized by a simple and low-cost method using Couroupita guianensis plant leaf extract. The particles were used as photocatalysts for degrading RhB, MO dyes, and TC antibiotics, as well as for reducing toxic 4-NP to useful 4-AP. The synthesized nanoparticles were characterized using several state-of-the-art tools. The formation of perovskite structure and the presence of biomolecules on the surface of BiFeO3 nanoparticles were confirmed by FTIR analysis. Raman spectrum revealed a rhombohedral structure of BiFeO3 nanoparticles, corroborating the XRD findings. FESEM micrograph demonstrated irregularly shaped agglomerated nanoparticles. The average hydrodynamic diameter was estimated to be 51 nm using the DLS technique. The optical energy bandgap of the bismuth ferrite was estimated using Tauc’s relation for direct bandgap semiconductors. SQUID measurements revealed that these nanoparticles exhibit a weak ferromagnetic ordering. Furthermore, these nanomaterials degraded the cationic and anionic dyes effectively because of the formation of hydroxyl radicals, confirmed by the scavenger test. The photocatalytic degradation pathway of RhB dye was investigated through LC-MS analysis, and the intermediate degradation products were identified. The prepared material also exhibited excellent catalytic reduction efficiency in a short duration of time. This study proclaims that these nanoparticles can be used as potential catalysts for the purification of water bodies.

Biodegradation of imidacloprid and diuron by Simplicillium sp. QHSH-33

Imidacloprid (IMI) and diuron (DIU) are widely used pesticides in agricultural production. However, their excessive use and high residues have caused harm to the ecological environment and human health. Microbial remediation as an efficient and low-toxic method has become a research hotspot for controlling environmental pollutants. A fungus QHSH-33, identified as Simplicillium sp., has the ability to degrade neonicotinoids IMI and phenylurea DIU. When QHSH-33 and pesticide were co-cultured in liquid medium for 7 days, the degradation rates of IMI and DIU by QHSH-33 in simulated field soil microenvironment were 50.19 % and 70.57 %, respectively. Through HPLC-MS analysis, it was found that the degradation of IMI mainly involved nitro reduction, hydroxylation and other reactions. Three degradation pathways and eight degradation products were identified, among which two metabolites were obtained by microbial transformation of IMI for the first time. The degradation of DIU mainly involved demethylation and dehalogenation reactions, and two degradation pathways and four degradation products were identified, one of which was a new degradation product of DIU. Toxicity assessment demonstrated that most of the degradation products might be considerably less harmful than IMI and DIU. Whole genome sequencing of QHSH-33 revealed a genome size of 33.2 Mbp with 11,707 genes. The genome of QHSH-33 was annotated by KEGG to reveal 128 genes related to exogenous degradation and metabolism. After local blast with reported IMI and DIU degrading enzymes, seven IMI-degrading related genes and seven DIU-degrading related genes were identified in the QHSH-33 genome. The results of this study will help to expand our knowledge on the microbial decomposition metabolism of IMI and DIU, and provide new insights into the degradation mechanism of IMI and DIU in soil and pure culture system, laying a foundation for QHSH-33 strain applied to the removal, biotransformation or detoxification of IMI and DIU.

Improving sugar and respiratory metabolism in pear wounds by postharvest dipping with chitosan and chitooligosaccharide

Chitosan (CTS) and its degradation product, chitooligosaccharide (COS), promote fruit healing by activating phenylpropanoid metabolism. This study investigates their effects on sucrose metabolism in pear wounds. CTS and COS were found to activate neutral invertase, acid invertase, sucrose synthase, and sucrose phosphate synthase, increasing sucrose, glucose, and fructose levels in fruit wounds. They also enhanced sorbitol dehydrogenase activity and promoted sorbitol accumulation. In addition, CTS and COS improved the activities of hexokinase, phosphofructokinase, and pyruvate kinase, increasing phosphoenolpyruvate and ATP production. They activated glucose-6-phosphate dehydrogenase and increased erythrose-4-phosphate, NADPH, and shikimic acid levels. In conclusion, CTS and COS support the formation of the healing closing layer by supplying carbon skeletons, energy, and reducing power through the activation of sugar and respiratory metabolism during the healing process. Compared to CTS, COS was superior in activating the above metabolisms, which is expected to be widely used as a chitin product in postharvest fruit and vegetable preservation and provide new insights into preserving pear freshness.

Antimicrobial Resistance: What Lies Beneath This Complex Phenomenon?

Antimicrobial Resistance (AMR) has evolved from a mere concern into a significant global threat, with profound implications for public health, healthcare systems, and the global economy. Since the introduction of antibiotics between 1945 and 1963, their widespread and often indiscriminate use in human medicine, agriculture, and animal husbandry has led to the emergence and rapid spread of antibiotic-resistant genes. Bacteria have developed sophisticated mechanisms to evade the effects of antibiotics, including drug uptake limitation, drug degradation, target modification, efflux pumps, biofilm formation, and outer membrane vesicles production. As a result, AMR now poses a threat comparable to climate change and the COVID-19 pandemic, and projections suggest that death rates will be up to 10 million deaths annually by 2050, along with a staggering economic cost exceeding $100 trillion. Addressing AMR requires a multifaceted approach, including the development of new antibiotics, alternative therapies, and a significant shift in antibiotic usage and regulation. Enhancing global surveillance systems, increasing public awareness, and prioritizing investments in research, diagnostics, and vaccines are critical steps. By recognizing the gravity of the AMR threat and committing to collaborative action, its impact can be mitigated, and global health can be protected for future generations.

Simultaneous Overcoming Approach for Poor Wettability and Low Stability in Stomach by Simple Methods; Formulation Design and Development of Monoacylglycerol Acyltransferase 2 Inhibitor, S-309309.

N-[(4R)-5,7-Difluoro-2'-(5-methylpyridin-2-yl)-4'-oxo-2,2',3,4',5',7'-hexahydrospiro[1-benzopyran-4,6'-pyrazolo[4,3-c]pyridin]-3'-yl]-2-(methanesulfonyl)acetamide (S-309309) is an anti-obesity drug developed by Shionogi & Co., Ltd. that has a monoacylglycerol acyltransferase 2 inhibitory effect. S-309309 has poor wettability, and the amount of the degradation product (4R)-3'-amino-5,7-difluoro-2'-(5-methylpyridin-2-yl)-2,2',3,7'-tetrahydrospiro[[1]benzopyran-4,6'-pyrazolo[4,3-c]pyridin]-4'(5'H)-one (compound 8) increases over time under acidic conditions. In this study, we have tried to improve S-309309 wettability and suppress the amount of degradation product increased under acidic conditions. As a result of the study, we found that by mixing with a water-soluble polymer, the wettability of S-309309 and its dissolved concentration in fluid were increased suggesting that its dissolution behavior should be enhanced. In addition, by encapsulating S-309309, the increase of degradation product amount was suppressed under acidic conditions, suggesting that the suppression of degradation product formation would be expected in the stomach after oral dosing. Overall, these results suggest that the drug property issues of S-309309 can be overcome by mixing S-309309 with a water-soluble polymer and encapsulation.

Redefining space pharmacology: bridging knowledge gaps in drug efficacy and safety for deep space missions

The space environment is incredibly hostile, and humans are vulnerable in such conditions. Astronauts encounter various stress factors during a space journey, including radiation, microgravity, forceful acceleration during launch, altered magnetic fields, and confinement. These stressors significantly impact the human body homeostasis, leading to physio-pathological adaptations, loss of bone density, muscle atrophy, cardiovascular deconditioning, alterations in liver function, vestibular adaptations, and immune system dysregulation. These alterations can potentially influence drug pharmacokinetics and pharmacodynamics, affecting the efficacy and safety of medications administered to astronauts. Due to the limited number of studies on pharmaceuticals conducted in microgravity conditions, it’s challenging to assess the effectiveness and stability of these medications during spaceflight. The objective of the present work is to compare the state-of-the-art knowledge on PK/PD changes and factors likely to affect them during spaceflight, with the subjective perception of the problem by a collection of separate interviews conducted with seven experts in the field. The interviewees were chosen as “experts,” i.e., representatives in a specific discipline, who possess knowledge and experience in space pharmacology, physiology, or biology. Thus, our panel included astronauts, space surgeons, and scientists aiming to bridge the lack of experimental data in the literature. Each interview explores assorted aspects of space physiology and pharmacology, including drug use and storage onboard the ISS; notable consideration has arisen regarding the current research gaps and future space expeditions. All the interviews were held remotely using online conferencing software. None of the interviewees could provide a comprehensive overview regarding potential changes in drugs PK/PD in microgravity conditions. Further, any medication brought on board (whether as part of an astronaut’s medical kit or stored in the ISS pharmacy) is destroyed, thereby suppressing the possibility of analyzing any degradation products resulting from long-term exposure to microgravity and radiation. According to these results, the use of drugs without understanding how they are genuinely absorbed, distributed, metabolized, and excreted in microgravity conditions is concerning, posing risks for drug effectiveness. Conducting genotyping and phenotyping on astronauts would be beneficial for developing personalized pharmacological countermeasures for each astronaut and anticipating expected drug metabolism changes during space missions.

Ecologically friendly remediation of groundwater sulfamethoxazole contamination: Biologically synergistic degradation by thermally modified activated carbon-activated peracetic acid in porous media

This study examines the efficacy and environmental impact of peracetic acid (PAA) activated by thermally modified activated carbon (AC600) for degrading antibiotics in actual groundwater. Laboratory-scale experiments evaluated the system's effects on contaminant degradation, ecological balance, and substance cycling in the hyporheic zone. Our findings demonstrated the effectiveness of the AC600/PAA system in removing sulfamethoxazole (SMX) from groundwater porous media. Additionally, the AC600/PAA system synergistically interacted with the in-situ microbiota of the hyporheic zone, producing more fragmented degradation products without increasing mixed toxicity. Bacterial abundance increased post-reaction, with notable alterations in the bacterial community and enhanced bacterial metabolism. Key genera such as Lysobacter thrived in the treated environment, playing critical roles in microbiota modification and SMX degradation. The pH remained stable before and after the reaction, while dissolved organic carbon content increased. Overall, our results highlight the promising potential of PAA activation by carbonaceous materials as a low-impact, ecologically friendly technology for in-situ remediation of organic pollutants in groundwater, characterized by high compatibility and biosynthesis.

Characterization of disulfide bridges containing cyclic peptide Linaclotide and its degradation products by using LC-HRMS/MS

Linaclotide (LINA) is a first-in-class guanylate cyclase agonist used for treating irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation. Stress degradation studies were performed to examine LINA's intrinsic stability, adhering to International Council for Harmonisation of Technical ICH) guidelines Q1A (R2). The current study endeavours to elucidate the stability behavior of LINA by exposing various stress conditions. A simple LC method was developed for effective separation of all LINA degradation products using a Waters Symmetry C18 column (150 ×4.6 mm, 3.5 µm) as the stationary phase. The generated degradation products were identified and characterized by using high-resolution mass spectrometry (LC-HRMS), MS/MS studies. The mechanistic fragmentation pathway for the seven degradation products was established and the chemical structure for the identified degradation products was elucidated. LINA was susceptible to degrade under acidic, basic, neutral, photolytic, and oxidative conditions. A total of three Pseudo DPs, DP-1, DP-2, and DP-3, were formed under acidic conditions while using methanol as the co-solvent. Additionally, degradation products (DPs) were identified: DP-4 formed under basic stress condition and DP-5 under neutral, thermal, and photolytic conditions. Furthermore, DP-6 and DP-7 were formed under oxidative stress condition. This study established the mechanistic fragmentation pathways and elucidated the chemical structures of the degradation products, offering valuable insights for generics and novel formulation drug development.