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Outer membrane vesicles (OMVs) are nano-sized vesicles actively released by Gram-negative bacteria, playing a crucial role in bacterial survival and interactions with phages. This review focuses on OMVs and succinctly delineates the stimuli instigating OMV formation, their functional repertoire, and their involvement in bacterial-phage interplays. Initially, the discussion centers on the drivers prompting OMV genesis, encompassing both extrinsic environmental pressures and intrinsic regulatory mechanisms within bacterial systems. Subsequently, a comprehensive examination of OMVs’ multifaceted functions in bacterial physiology ensues, spanning signaling cascades, nutrient transport, antibiotic resilience, and evasion of immune surveillance. Particular emphasis is placed on elucidating the paramount significance of OMVs in mediating bacterial-phage dynamics. OMVs function as decoys, providing protection to bacterial hosts against phages, and concurrently promoting the spread of phage receptors, thereby rendering phage-resistant strains susceptible to phage invasion. This comprehensive review deepens our comprehension of membrane vesicles biogenesis in bacteria and their pivotal role in microbial community dynamics. [ABSTRACT FROM AUTHOR]

Abstract Background Acute cardiac injury caused by coronavirus disease 2019 (COVID-19) increases mortality. Acute cardiac injury caused by COVID-19 requires understanding how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) directly infects cardiomyocytes. This study provides a solid foundation for related studies by using a model of SARS-CoV-2 infection in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) at the transcriptome level, highlighting the relevance of this study to related studies. SARS-CoV-2 infection in hiPSC-CMs has previously been studied by bioinformatics without presenting the full molecular biological process. We present a unique bioinformatics view of the complete molecular biological process of SARS-CoV-2 infection in hiPSC-CMs. Methods To validate the RNA-seq datasets, we used GSE184715 and GSE150392 for the analytical studies, GSE193722 for validation at the cellular level, and GSE169241 for validation in heart tissue samples. GeneCards and MsigDB databases were used to find genes associated with the phenotype. In addition to differential expression analysis and principal component analysis (PCA), we also performed protein-protein interaction (PPI) analysis, functional enrichment analysis, hub gene analysis, upstream transcription factor prediction, and drug prediction. Results Differentially expressed genes (DEGs) were classified into four categories: cardiomyocyte cytoskeletal protein inhibition, proto-oncogene activation and inflammation, mitochondrial dysfunction, and intracellular cytoplasmic physiological function. Each of the hub genes showed good diagnostic prediction, which was well validated in other datasets. Inhibited biological functions included cardiomyocyte cytoskeletal proteins, adenosine triphosphate (ATP) synthesis and electron transport chain (ETC), glucose metabolism, amino acid metabolism, fatty acid metabolism, pyruvate metabolism, citric acid cycle, nucleic acid metabolism, replication, transcription, translation, ubiquitination, autophagy, and cellular transport. Proto-oncogenes, inflammation, nuclear factor-kappaB (NF-κB) pathways, and interferon signaling were activated, as well as inflammatory factors. Viral infection activates multiple pathways, including the interferon pathway, proto-oncogenes and mitochondrial oxidative stress, while inhibiting cardiomyocyte backbone proteins and energy metabolism. Infection limits intracellular synthesis and metabolism, as well as the raw materials for mitochondrial energy synthesis. Mitochondrial dysfunction and energy abnormalities are ultimately caused by proto-oncogene activation and SARS-CoV-2 infection. Activation of the interferon pathway, proto-oncogene up-regulation, and mitochondrial oxidative stress cause the inflammatory response and lead to diminished cardiomyocyte contraction. Replication, transcription, translation, ubiquitination, autophagy, and cellular transport are among the functions that decline physiologically. Conclusion SARS-CoV-2 infection in hiPSC-CMs is fundamentally mediated via mitochondrial dysfunction. Therapeutic interventions targeting mitochondrial dysfunction may alleviate the cardiovascular complications associated with SARS-CoV-2 infection.

Pyrazole scaffolds have emerged as a promising frontier in drug discovery, offering a rich source of chemical diversity and pharmacological activity. This review explores the synthesis, biological significance, medicinal chemistry strategies, computational approaches, recent advances, and future perspectives of pyrazole-based compounds in pharmacotherapy. The chemical structure and properties of pyrazole scaffolds are examined, highlighting their structural characteristics, physicochemical properties and synthetic routes. The biological significance of pyrazole derivatives is elucidated through an exploration of their targeted receptors, pharmacological activities, and therapeutic potential in anticancer, anti-inflammatory, antimicrobial, and other disease contexts. Medicinal chemistry strategies utilizing pyrazole scaffolds, including structureactivity relationship studies, pharmacophore mapping, and molecular docking simulations, are discussed for rational drug design and optimization. Case studies of pyrazole-derived drugs, emerging trends and applications are presented to underscore the diverse pharmacological activities and clinical applications of pyrazole-based compounds. Computational approaches in pyrazole-based drug design, such as molecular modeling techniques, virtual screening methods and quantitative structureactivity relationship studies, are examined for their role in accelerating the discovery and optimization of novel therapeutics. Future perspectives on the potential for future drug development, integration with emerging technologies and concluding remarks highlight the significance of pyrazole scaffolds in addressing unmet medical needs and advancing precision medicine. In conclusion, pyrazole scaffolds represent a promising avenue for the development of novel therapeutics with enhanced efficacy, selectivity and safety profiles, shaping the future of pharmacotherapy in the evolving landscape of modern medicine. [ABSTRACT FROM AUTHOR]

Background: Acute cardiac injury caused by coronavirus disease 2019 (COVID-19) increases mortality. Acute cardiac injury caused by COVID-19 requires understanding how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) directly infects cardiomyocytes. This study provides a solid foundation for related studies by using a model of SARS-CoV-2 infection in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) at the transcriptome level, highlighting the relevance of this study to related studies. SARS-CoV-2 infection in hiPSC-CMs has previously been studied by bioinformatics without presenting the full molecular biological process. We present a unique bioinformatics view of the complete molecular biological process of SARS-CoV-2 infection in hiPSC-CMs. Methods: To validate the RNA-seq datasets, we used GSE184715 and GSE150392 for the analytical studies, GSE193722 for validation at the cellular level, and GSE169241 for validation in heart tissue samples. GeneCards and MsigDB databases were used to find genes associated with the phenotype. In addition to differential expression analysis and principal component analysis (PCA), we also performed protein-protein interaction (PPI) analysis, functional enrichment analysis, hub gene analysis, upstream transcription factor prediction, and drug prediction. Results: Differentially expressed genes (DEGs) were classified into four categories: cardiomyocyte cytoskeletal protein inhibition, proto-oncogene activation and inflammation, mitochondrial dysfunction, and intracellular cytoplasmic physiological function. Each of the hub genes showed good diagnostic prediction, which was well validated in other datasets. Inhibited biological functions included cardiomyocyte cytoskeletal proteins, adenosine triphosphate (ATP) synthesis and electron transport chain (ETC), glucose metabolism, amino acid metabolism, fatty acid metabolism, pyruvate metabolism, citric acid cycle, nucleic acid metabolism, replication, transcription, translation, ubiquitination, autophagy, and cellular transport. Proto-oncogenes, inflammation, nuclear factor-kappaB (NF-κB) pathways, and interferon signaling were activated, as well as inflammatory factors. Viral infection activates multiple pathways, including the interferon pathway, proto-oncogenes and mitochondrial oxidative stress, while inhibiting cardiomyocyte backbone proteins and energy metabolism. Infection limits intracellular synthesis and metabolism, as well as the raw materials for mitochondrial energy synthesis. Mitochondrial dysfunction and energy abnormalities are ultimately caused by proto-oncogene activation and SARS-CoV-2 infection. Activation of the interferon pathway, proto-oncogene up-regulation, and mitochondrial oxidative stress cause the inflammatory response and lead to diminished cardiomyocyte contraction. Replication, transcription, translation, ubiquitination, autophagy, and cellular transport are among the functions that decline physiologically. Conclusion: SARS-CoV-2 infection in hiPSC-CMs is fundamentally mediated via mitochondrial dysfunction. Therapeutic interventions targeting mitochondrial dysfunction may alleviate the cardiovascular complications associated with SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Glioma represents a complex and heterogeneous disease, posing significant challenges to both clinicians and researchers. Despite notable advancements in glioma treatment, the overall survival rate for most glioma patients remains dishearteningly low. Hence, there is an urgent necessity to discover novel biomarkers and therapeutic targets specifically tailored for glioma. In recent years, long non-coding RNAs (lncRNAs) have emerged as pivotal regulators of gene expression and have garnered attention for their involvement in the development and progression of various cancers, including glioma. The dysregulation of lncRNAs plays a critical role in glioma pathogenesis and influences clinical outcomes. Consequently, there is growing interest in exploring the potential of lncRNAs as diagnostic and prognostic biomarkers, as well as therapeutic targets. By understanding the functions and dysregulation of lncRNAs in glioma, researchers aim to unlock new avenues for the development of innovative treatment strategies catered to glioma patients. The identification and thorough characterization of lncRNAs hold the promise of novel therapeutic approaches that could potentially improve patient outcomes and enhance the management of glioma, ultimately striving for better prospects and enhanced quality of life for those affected by this challenging disease. The primary objective of this paper is to comprehensively review the current state of knowledge regarding lncRNA biology and their intricate roles in glioma. It also delves into the potential of lncRNAs as valuable diagnostic and prognostic indicators and explores their feasibility as promising targets for therapeutic interventions.

The interpretation of massive high-throughput gene expression data requires computational and biological analyses to identify statistically and biologically significant differences, respectively. There are abundant sources that describe computational tools for statistical analysis of massive gene expression data but few address data analysis for biological significance. In the present article we exemplify the importance of selecting the proper biological context in the human brain for gene expression data analysis and interpretation. For this purpose, we use cortical type as conceptual tool to make predictions about gene expression in areas of the human temporal cortex. We predict that the expression of genes related to glutamatergic transmission would be higher in areas of simpler cortical type, the expression of genes related to GABAergic transmission would be higher in areas of more complex cortical type, and the expression of genes related to epigenetic regulation would be higher in areas of simpler cortical type. Then, we test these predictions with gene expression data from several regions of the human temporal cortex obtained from the Allen Human Brain Atlas. We find that the expression of several genes shows statistically significant differences in agreement with the predicted gradual expression along the laminar complexity gradient of the human cortex, suggesting that simpler cortical types may have greater glutamatergic excitability and epigenetic turnover compared to more complex types; on the other hand, complex cortical types seem to have greater GABAergic inhibitory control compared to simpler types. Our results show that cortical type is a good predictor of synaptic plasticity, epigenetic turnover, and selective vulnerability in human cortical areas. Thus, cortical type can provide a meaningful context for interpreting high-throughput gene expression data in the human cerebral cortex. [ABSTRACT FROM AUTHOR]

Menaquinone-7 (MK-7) is the most therapeutically valuable K vitamin owing to its excellent bioavailability. MK-7 occurs as geometric isomers, and only all-trans MK-7 is bioactive. The fermentation-based synthesis of MK-7 entails various challenges, primarily the low fermentation yield and numerous downstream processing steps. This raises the cost of production and translates to an expensive final product that is not widely accessible. Iron oxide nanoparticles (IONPs) can potentially overcome these obstacles due to their ability to enhance fermentation productivity and enable process intensification. Nevertheless, utilisation of IONPs in this regard is only beneficial if the biologically active isomer is achieved in the greatest proportion, the investigation of which constituted the objective of this study. IONPs (Fe3O4) with an average size of 11 nm were synthesised and characterised using different analytical techniques, and their effect on isomer production and bacterial growth was assessed. The optimum IONP concentration (300 μg/mL) improved the process output and resulted in a 1.6-fold increase in the all-trans isomer yield compared to the control. This investigation was the first to evaluate the role of IONPs in the synthesis of MK-7 isomers, and its outcomes will assist the development of an efficient fermentation system that favours the production of bioactive MK-7. [ABSTRACT FROM AUTHOR]

The interpretation of massive high-throughput gene expression data requires computational and biological analyses to identify statistically and biologically significant differences, respectively. There are abundant sources that describe computational tools for statistical analysis of massive gene expression data but few address data analysis for biological significance. In the present article we exemplify the importance of selecting the proper biological context in the human brain for gene expression data analysis and interpretation. For this purpose, we use cortical type as conceptual tool to make predictions about gene expression in areas of the human temporal cortex. We predict that the expression of genes related to glutamatergic transmission would be higher in areas of simpler cortical type, the expression of genes related to GABAergic transmission would be higher in areas of more complex cortical type, and the expression of genes related to epigenetic regulation would be higher in areas of simpler cortical type. Then, we test these predictions with gene expression data from several regions of the human temporal cortex obtained from the Allen Human Brain Atlas. We find that the expression of several genes shows statistically significant differences in agreement with the predicted gradual expression along the laminar complexity gradient of the human cortex, suggesting that simpler cortical types may have greater glutamatergic excitability and epigenetic turnover compared to more complex types; on the other hand, complex cortical types seem to have greater GABAergic inhibitory control compared to simpler types. Our results show that cortical type is a good predictor of synaptic plasticity, epigenetic turnover, and selective vulnerability in human cortical areas. Thus, cortical type can provide a meaningful context for interpreting high-throughput gene expression data in the human cerebral cortex.

The microarray data contains the high volume of genes having multiple values of expressions and small number of samples. Therefore, the selection of gene from microarray data is an extremely challenging and important issue to analyze the biological behavior of features. In this context, dynamic scaling factor based differential evolution (DE) with multi-layer perceptron (MLP) is designed for selection of genes from pathway information of microarray data. At first DE is employed to select the relevant and lesser number of genes. Then MLP is used to build a classifier model over the selected genes. A suitable and efficient representation of vector is designed for DE. The fitness function is derived separately as T-score, classification accuracy and weight sum approach of both. Simulation and further analysis is performed in terms of sensitivity, specificity, accuracy and F-score. Moreover, statistical and biological analysis are also conducted. [ABSTRACT FROM AUTHOR]

As a multifunctional protein, the hemagglutinin-neuraminidase (HN) protein of Newcastle disease virus (NDV) is involved in various biological functions. A velogenic genotype III NDV JS/7/05/Ch evolving from the mesogenic vaccine strain Mukteswar showed major amino acid (aa) mutations in the HN protein. However, the precise biological significance of the mutant HN protein remains unclear. This study sought to investigate the effects of the mutant HN protein on biological activities in vitro and in vivo. The mutant HN protein (JS/7/05/Ch-type HN) significantly enhanced the hemadsorption (HAd) and fusion promotion activities but impaired the neuraminidase (NA) activity compared with the original HN protein (Mukteswar-type HN). Notably, A494D and E495K in HN exhibited a synergistic role in regulating biological activities. Moreover, the mutant HN protein, especially A494D and E495K in HN, enhanced the F protein cleavage level, which can contribute to the activation of the F protein. In vitro infection assays further showed that NDVs bearing A494D and E495K in HN markedly impaired the cell viability. Simultaneously, A494D and E495K in HN enhanced virus replication levels at the early stage of infection but weakened later in infection, which might be associated with the attenuated NA activity and cell viability. Furthermore, the animal experiments showed that A494D and E495K in HN enhanced case fatality rates, virus shedding, virus circulation, and histopathological damages in NDV-infected chickens. Overall, these findings highlight the importance of crucial aa mutations in HN in regulating biological activities of NDV and expand the understanding of the enhanced pathogenicity of the genotype III NDV. [ABSTRACT FROM AUTHOR]

Coevolution of living things and their surroundings contributes to the biodiversity on Earth. Combining with the abiotic-biotic regulatory concept, the Gaia theory, and the philosophical view in ancient China, we believe the physical river evolution must somehow takes on biological evolution characteristics, and the river biosphere could be an anti-entropic system and develop towards the higher beings. Here, beyond the traditional understanding of river, we redefine a kind of systematic out-branching (Dragon style) river which is characterized by a systematic connection between the stable, unobstructed main-channel and the active, open, abducent out-branches under some high-resistant environmental conditions (especially in tropical and polar zones). It has the potential to help detect the signatures of life on other planets which are similar in river landscape to Earth. [ABSTRACT FROM AUTHOR]

Histones are important component of eukaryotic cells chromatin and consist of arginine and lysine residues. Histones play an important role in the protection of DNA. Their contents significantly affect high-level chromatin structure formation, gene expression, DNA replication, and other important life activities. Protein degradation is an important regulatory mechanism of histone content. Recent studies have revealed that modification of amino acid sequence is directly related to histone breakdown. In addition, histone degradation is closely related to covalent modifications, such as ubiquitination and acetylation, which are considered to be driving factors in gene regulation. Gene regulation is an important mechanism in adaptation to the environment and survival of species. With the introduction of highly efficient technology, various mutations in histones have been identified in yeast. In the field of epigenetics and the transmission of chromatin states, two widely used model organisms are the budding yeast Saccharomyces cerevisiae and Schizosaccharomyces pombe. Higher eukaryotes can use their silent loci to maintain their epigenetic states and providing the base to investigate mechanisms underlying development. Therfore, both species have contributed a plethora of information on these mechanisms in both yeast and higher eukaryotes. This study focuses on the role of histone modifications in controlling telomeric silencing in Saccharomyces cerevisiae and centromeric silencing in S. pombe as examples of genetic loci that demonstrate epigenetic inheritance. In view of recent advances, this review focuses on the post-translational modification of histone amino acid residues and reviews the relationship between histone degradation and amino acid residue modification. [ABSTRACT FROM AUTHOR]

The kinetics of the aqueous reaction, between pH values of 0–4 & 7–14, have been determined for a series of carbinol substituted N‐(α‐hydroxybenzyl)benzamide derivatives (5), in H2O, at 25 °C, I=1.0 M (KCl). The carbinol derivatives of 5 were found to react via two mechanisms. Between pH values of 0 to 4, an acid‐catalyzed mechanism was found and under neutral/basic conditions the carbinolamides reacted by a specific‐base catalyzed mechanism (E1cB‐like mechanism). No evidence for mechanistic variation of the acid and base‐catalyzed reactions based upon the carbinol substituent was found. The rate constants are reported for the acid‐catalyzed (kH, ρ=−1.89), the apparent second‐order hydroxide rate constant (k'1, ρ=−0.16), hydroxide limiting rate (k1, ρ=−0.93) and the pKa's of the hydroxyl group (ρ=0.77) for seven carbinol substituted derivatives of 5. The ρ‐values for the carbinol derivatives of 5 will be compared to the previously reported ρ‐values for the structurally similar amide substituted derivatives. [ABSTRACT FROM AUTHOR]

PurposeOur research was aimed to identify the expression, clinical value and biological significance of GINS complex subunit 4 (GINS4) in hepatocellular carcinoma (HCC).Materials and MethodsGINS4 was initially screened through weighted gene co-expression network analysis (WGCNA). The TCGA, GEO, and TIMER databases were applied for analyzing the GINS4 mRNA expression in HCC. GINS4 protein levels were detected via immunohistochemistry (IHC). Receiver operating characteristic (ROC) curve was applied for estimating the diagnostic significance of GINS4 in HCC. Kaplan-Meier plots, Cox model, and nomogram were used to assess the prognostic performance of GINS4 in HCC. Nomogram validation was conducted through time-dependent ROC and decision curve analysis (DCA). The Wanderer, UALCAN, and DiseaseMeth databases were utilized to identify GINS4 methylation levels in HCC. Genes co-expressed with GINS4 in HCC were estimated through the TCGA, cBioPortal, and GEPIA. GO, KEGG, and GSEA unraveled the possible biological mechanisms of GINS4 in HCC.ResultsWGCNA confirmed that GINS4 was one of hub genes significantly associated with histological grade of HCC. Multiple databases confirmed the significant upregulation of GINS4 in HCC tissues compared with non-tumor controls. IHC analysis of 35 HCC patients demonstrated that overexpressed GINS4 positively correlated with advanced TNM stage and poor pathological differentiation. GINS4 could effectively differentiate HCC cases from healthy individuals, with an AUC of 0.865. Increased GINS4 expression predicted unsatisfactory prognosis in HCC patients, especially in age >60 years, histological grade 1, HBV infection-negative, and occurring relapse subgroup. Nomogram incorporating GINS4 level and TNM stage displayed satisfactory predictive accuracy and clinical utility in predicting HCC prognosis. Upregulated GINS4 exhibited hypomethylated levels in HCC. Functional analysis indicated that GINS4 potentially positively modulated cell cycle and PI3K/AKT/mTOR pathway.ConclusionGINS4 is overexpressed in HCC and is correlated with undesirable survival of HCC patients.

Purpose: Our research was aimed to identify the expression, clinical value and biological significance of GINS complex subunit 4 (GINS4) in hepatocellular carcinoma (HCC). Materials and Methods: GINS4 was initially screened through weighted gene co-expression network analysis (WGCNA). The TCGA, GEO, and TIMER databases were applied for analyzing the GINS4 mRNA expression in HCC. GINS4 protein levels were detected via immunohistochemistry (IHC). Receiver operating characteristic (ROC) curve was applied for estimating the diagnostic significance of GINS4 in HCC. Kaplan-Meier plots, Cox model, and nomogram were used to assess the prognostic performance of GINS4 in HCC. Nomogram validation was conducted through time-dependent ROC and decision curve analysis (DCA). The Wanderer, UALCAN, and DiseaseMeth databases were utilized to identify GINS4 methylation levels in HCC. Genes co-expressed with GINS4 in HCC were estimated through the TCGA, cBioPortal, and GEPIA. GO, KEGG, and GSEA unraveled the possible biological mechanisms of GINS4 in HCC. Results: WGCNA confirmed that GINS4 was one of hub genes significantly associated with histological grade of HCC. Multiple databases confirmed the significant upregulation of GINS4 in HCC tissues compared with non-tumor controls. IHC analysis of 35 HCC patients demonstrated that overexpressed GINS4 positively correlated with advanced TNM stage and poor pathological differentiation. GINS4 could effectively differentiate HCC cases from healthy individuals, with an AUC of 0.865. Increased GINS4 expression predicted unsatisfactory prognosis in HCC patients, especially in age >60 years, histological grade 1, HBV infection-negative, and occurring relapse subgroup. Nomogram incorporating GINS4 level and TNM stage displayed satisfactory predictive accuracy and clinical utility in predicting HCC prognosis. Upregulated GINS4 exhibited hypomethylated levels in HCC. Functional analysis indicated that GINS4 potentially positively modulated cell cycle and PI3K/AKT/mTOR pathway. Conclusion: GINS4 is overexpressed in HCC and is correlated with undesirable survival of HCC patients. [ABSTRACT FROM AUTHOR]

The study on plant natural products not only helps us understand that their structural diversity is the inevitable result of plant species diversity, but also helps us understand certain rules and unity of the inevitable connection between the two. The diversity and complexity of chemical structures of many natural products are beyond imagination before we elucidated their structures. The question that follows is what is the biological significance of these natural products. Intrigued by the relationship between plant resources, natural products and biological functions, the Hao laboratory has taken an integrative approach that employs tools and knowledge from multi-disciplines, including natural product chemistry, chemical ecology and chemical biology, to unveil the effects of plant natural products on plant resistance to diseases, and environmental acclimations. Collaborating with cell biologists, the research has resulted in discovery of new mechanisms of cellular signaling and lead compounds. [ABSTRACT FROM AUTHOR]

Over the last 10 years, there has been a plethora of experimental studies estimating the potential of microplastic particles (MPs) to exert toxic effects in the environment, many specifically focusing on their postulated capacity to enhance the transfer of environmental pollutants into organisms after ingestion. Obviously, there is little to no consensus on appropriate experimental design, which is mainly owing to the novelty, the interdisciplinarity of the subject, and the complexity of parameters involved. This results in fundamental discrepancies regarding the materials applied, the approach for spiking MPs with pollutants, and the exact exposure scenario. Aiming for a non-chemist audience and providing illustrative, representative, and comparative examples, this review first outlines the theoretical essentials of processes involved in sorption. Also, it discusses the implications for designing experimental approaches using MPs and interpreting the results obtained under consideration of their relevance for environmental conditions. It may help to improve the interpretation of studies on MP toxicity already published, while also calling experimenters' attention to various aspects important to consider when designing and performing environmentally relevant experiments with MPs. [ABSTRACT FROM AUTHOR]

Chloramphenicol (CAP) is an antibiotic that commonly pollutes the environment, and microorganisms primarily drive its degradation and transformation. Although several pathways for CAP degradation have been documented in different bacteria, multiple metabolic pathways in the same strain and their potential biological significance have not been revealed. In this study, Sphingobium WTD-1, which was isolated from activated sludge, can completely degrade 100 mg/L CAP within 60 h as the sole energy source. UPLC-HRMS and HPLC analyses showed that three different pathways, including acetylation, hydroxyl oxidation, and oxidation (C1-C2 bond cleavage), are responsible for the metabolism of CAP. Importantly, acetylation and C3 hydroxyl oxidation reduced the cytotoxicity of the substrate to strain WTD-1, and the C1-C2 bond fracture of CAP generated the metabolite p -nitrobenzoic acid (PNBA) to provide energy for its growth. This indicated that the synergistic action of three metabolic pathways caused WTD-1 to be adaptable and able to degrade high concentrations of CAP in the environment. This study deepens our understanding of the microbial degradation pathway of CAP and highlights the biological significance of the synergistic metabolism of antibiotic pollutants by multiple pathways in the same strain. [Display omitted] • An efficient CAP-degrading strain Sphingobium sp. WTD-1 was isolated. • Coexistence of CAP acetylation, hydroxyl oxidation, and oxidation in strain WTD-1. • The biological significance of multiple metabolic pathways of CAP was revealed. • Strain WTD-1 is a promising candidate for practical bioremediation of wastewater. [ABSTRACT FROM AUTHOR]

The present study describes recent advances in the chemistry of heterocycles incorporated oxazolo[4,5-b]pyridine and oxazolo[5,4-b]pyridine skeletons. The main sections included the synthesis of the investigated compounds from readily accessible aminopyridinol derivatives or aminopyridines. The reactivity of substituents attached to ring carbon or nitrogen atoms were discussed. In addition, the synthetic and biological evaluation of the inspected oxazolopyridines were highlighted. The purpose of this review is to discuss the chemistry of the title so far. The present study will support researchers in the fields of organic and medicinal chemistry to design and develop new protocols for the construction of new biological components. [ABSTRACT FROM AUTHOR]

Steroids are perhaps one of the most widely used group of drugs in present day. Beside the established utilization as immunosuppressive, anti-inflammatory, anti-rheumatic, progestational, diuretic, sedative, anabolic and contraceptive agents, recent applications of steroid compounds include the treatment of some forms of cancer, osteoporosis, HIV infections and treatment of declared AIDS. Steroids isolated are often available in minute amounts. So biotransformation of natural products provides a powerful means in solving supply problems in clinical trials and marketing of the drug for obtaining natural products in bulk amounts. If the structure is complex, it is often an impossible task to isolate enough of the natural products for clinical trials. The microbial biotransformation of steroids yielded several novel metabolites, exhibiting different activities. The metabolites produced from pregnenolone acetate by Cunning hamella elegans and Rhizopus stolonifer were screened against tyrosinase and cholinesterase showed significant inhibitory activities than the parent compound. Diosgenin and its transformed sarsasapogenin were screened for their acetyl cholinesterase and butyryl cholinesterase inhibitory activities. Sarsasapogenin was screened for phytotoxicity, and was found to be more active than the parent compound. Diosgenin, prednisone and their derivatives were screened for their anti-leishmanial activity. All derivatives were found to be more active than the parent compound. The biotransformation of steroids have been reviewed to a little extent. This review focuses on the biotransformation and functions of selected steroids, the classification, advantages and agents of enzymatic biotransformation and examines the potential role of new enzymatically transformed steroids and their derivatives in the chemoprevention and treatment of other diseases. tyrosinase and cholinesterase inhibitory activities, severe asthma, rheumatic disorders, renal disorders and diseases of inflammatory bowel, skin, gastrointestinal tract. [ABSTRACT FROM AUTHOR]

Cancer still remains a continued threat for human race in the 21st century. It is the major cause of human casualties globally and is thus, a hot topic of research in medicinal laboratories. Scientists are striving to find selective anticancer agents having low toxicity for normal human cells. Heterocyclic ring systems play key role as templates/pharmacophores for various drugs, and benzimidazole ring is especially important for its anticancer derivatives. In this review article, we have focused on the structural features of anticancer derivatives based on benzimidazole ring system. It highlights various benzimidazole-based anticancer compounds which have been developed in recent years. [ABSTRACT FROM AUTHOR]

Despite concerns on the effects of noise from seismic survey airguns on marine organisms, there remains uncertainty as to the biological significance of any response. This study quantifies and interprets the response of migrating humpback whales (Megaptera novaeangliae) to a 3130 in³ (51.3l) commercial airgun array. We compare the behavioural responses to active trials (array operational; n = 34 whale groups), with responses to control trials (source vessel towing the array while silent; n = 33) and baseline studies of normal behaviour in the absence of the vessel (n = 85). No abnormal behaviours were recorded during the trials. However, in response to the active seismic array and the controls, the whales displayed changes in behaviour. Changes in respiration rate were of a similar magnitude to changes in baseline groups being joined by other animals suggesting any change group energetics was within their behavioural repertoire. However, the reduced progression southwards in response to the active treatments, for some cohorts, was below typical migratory speeds. This response was more likely to occur within 4 km from the array at received levels over 135 dB re 1 μPa².s. [ABSTRACT FROM AUTHOR]