Structural Modifications Research Articles

SYNTHESIS, CHARACTERIZATION & BIOLOGICAL EVALUATION OF SOME FLUOROQUINOLONE DERIVATIVES AS ANTIMICROBIAL AGENTS

Fluoroquinolones, a class of synthetic antibacterial agents, have gained significant attention due to their broad-spectrum activity against various bacterial pathogens. However, the emergence of resistance to conventional fluoroquinolones underscores the necessity for novel derivatives with enhanced efficacy and reduced resistance profiles. The synthesis of fluoroquinolone derivatives involves structural modifications aimed at improving antimicrobial activity, pharmacokinetic properties, and minimizing adverse effects. Various synthetic routes, including modification of the quinolone core structure, substitution of fluorine atoms, and introduction of diverse functional groups, have been explored to tailor the properties of these derivatives. Characterization techniques such as infrared spectroscopy (IR) has been employed to elucidate the chemical structures and confirm the purity of synthesized compounds. Biological evaluation encompasses in vitro and in vivo studies to assess the antimicrobial activity, cytotoxicity, and pharmacological profiles of fluoroquinolone derivatives. These evaluations provide crucial insights into the therapeutic potential, mechanism of action, and safety profile of novel compounds.

Alkene Isomerization Using a Heterogeneous Nickel-Hydride Catalyst.

Transition metal-catalyzed alkene isomerization is an enabling technology used to install an alkene distal to its original site. Due to their well-defined structure, homogeneous catalysts can be fine-tuned to optimize reactivity, stereoselectivity, and positional selectivity, but they often suffer from instability and nonrecyclability. Heterogeneous catalysts are generally highly robust but continue to lack active-site specificity and are challenging to rationally improve through structural modification. Known single-site heterogeneous catalysts for alkene isomerization utilize precious metals and bespoke, expensive, and synthetically intense supports. Additionally, they generally have mediocre reactivity, inspiring us to develop a heterogeneous catalyst with an active site made from readily available compounds made of Earth-abundant elements. Previous work demonstrated that a very active homogeneous catalyst is formed upon protonation of Ni[P(OEt)3]4 by H2SO4, generating a [Ni-H]+ active site. This catalyst is incredibly active, but also decomposes readily, which severely limits its utility. Herein we show that by using a solid acid (sulfated zirconia, SZO300), not only is this decomposition prevented, but high activity is maintained, improved selectivity is achieved, and a broader scope of functional groups is tolerated. Preliminary mechanistic experiments suggest that the catalytic reaction likely goes through an intermolecular, two-electron pathway. A detailed kinetic study comparing the state-of-the-art Ni and Pd isomerization catalysts reveals that the highest activity and selectivity is seen with the Ni/SZO300 system. The reactivity of Ni/SZO300, is not limited to alkene isomerization; it is also a competent catalyst for hydroalkenylation, hydroboration, and hydrosilylation, demonstrating the broad application of this heterogeneous catalyst.

Effect of enzymatic modification on the structure and rheological properties of diluted alkali-soluble pectin fraction rich in RG-I

This study focuses on pectin covalently linked in cell walls from two sources, apples and carrots, that was extracted using diluted alkali, and it describes changes in the rheological properties of diluted alkali-soluble pectin (DASP) due to enzymatic treatment. Given DASP’s richness of rhamnogalacturonan I (RG-I), RG-I acetyl esterase (RGAE), rhamnogalacturonan endolyase (RGL), and arabinofuranosidase (ABF) were employed in various combinations for targeted degradation of RG-I pectin chains. Enzymatic degradations were followed by structural studies of pectin molecules using atomic force microscopy (AFM) as well as measurements of rheological and spectral properties. AFM imaging revealed a significant increase in the length of branched molecules after incubation with ABF, suggesting that arabinose side chains limit RG-I aggregation. Structural modifications were confirmed by changes in the intensity of bands in the pectin fingerprint and anomeric region on Fourier transform infrared spectra. ABF treatment led to a decrease in the stability of pectic gels, while the simultaneous use of ABF, RGAE, and RGL enzymes did not increase the degree of aggregation compared to the control sample. These findings suggest that the association of pectin chains within the DASP fraction may rely significantly on intermolecular interactions. Two mechanisms are proposed, which involve side chains as short-range attachment points or an extended linear homogalacturonan conformation favoring inter-chain interactions over self-association.

In Vivo and In Silico Molecular Modeling Studies of Newly Synthesized Pyrazoles for Their Anti-Inflammatory and Analgesic Properties

Background: Pyrazole derivatives have gained attention as potential leads for developing anti-inflammatory and analgesic drugs. Chemical modifications of pyrazole structures offer a strategy to enhance their therapeutic properties, while minimizing undesirable effects. Objective: This study aimed to synthesize novel pyrazole derivatives through chemical modifications and assess their anti-inflammatory and analgesic activities. Methods: A series of pyrazole variants were synthesized by reacting various acetophenone derivatives and diethyl oxalate in basic conditions, followed by treatment with glacial acetic acid and hydrazine hydrate. The resulting compounds were further methylated and acetylated. The synthesized compounds were characterized using elemental analysis, 1H NMR, IR, and MASS spectroscopy. The anti-inflammatory activity was evaluated using the rat paw edema technique induced by carrageenan, while the analgesic activity was assessed using the writhing reflux method. Results: Among the newly synthesized pyrazole derivatives, compounds 3b, 3e and 3g′ demonstrated significant anti-inflammatory activity with reduced ulcerogenic potential. Compounds 3d, 3b′ and 3d′ exhibited notable analgesic activity compared to the standard drug. The chemical modifications introduced in these derivatives were confirmed through spectroscopic analyses. Conclusion: The findings of this study highlight the potential of pyrazole derivatives as promising candidates for anti-inflammatory and analgesic drug development. The structural modifications performed in this research improved the therapeutic activities of the compounds, while addressing safety concerns. Further investigations are warranted to elucidate the underlying mechanisms of action and optimize the pharmacological profiles of these novel pyrazole derivatives.

Evolution of the Electrical Conductivity of LiNb1−xTaxO3 Solid Solutions across the Ferroelectric Phase Transformation

The investigation of the structural phase transition in the vicinity of the Curie temperature of crystals is motivated by the expected combination of advantageous high‐temperature properties of and , including high piezoelectric modules and remarkable high‐temperature stability, respectively. marks the ultimate limit for exploiting the piezoelectric properties; however, transition‐related structural modifications might impact this and other properties even below . Remarkably, the phase transition from the ferroelectric to the paraelectric phase, whose temperature strongly depends on the composition x, shows a significant drop in the activation energy of the electrical conductivity. The magnitude, temperature dependence, and underlying mechanisms of this drop are discussed from a microscopic perspective. Molecular dynamics calculations in the framework of the density functional theory show that substantial displacements of the cations occur below for both the end compounds and , and might thus affect the electrical conductivity. Above , the migration of lithium ions is presumably facilitated by a shortened diffusion path for the most favorable jump of the lithium ions. Electronic contributions to the conductivity, which become important above 900 K, are explained within the polaronic picture by the formation and migration of free small polarons.

Zinc–cobalt bimetallic metal-organic framework (Zn/Co-MOF) nanoparticles as potent pH stimuli anti-corrosive agent for development of a self-healable epoxy composite coating

The impressive BET-surface area and the design versatility have made Z67(ZIF-67) MOF a potent nanomaterial for anti-corrosion applications. Despite excellent anti-corrosion features the Z67(ZIF-67) suffers poor stability in water media, making it improper for application in polymeric systems. One strategy to enhance the stability of Z67 is its structure modification via a mixed-metal organic framework approach. This study involved the synthesis of a series of Z67 nanoparticles through the incorporation of zinc cation (Zn) at different percentages. Specifically, three different compositions were synthesized: Zn10-Z67, Zn20-Z67, and Zn30-Z67 denoting the addition of 10 %, 20 %, and 30 % molar percent of Zn, respectively. FTIR, FE-SEM, XRD, TEM, ICP-OES, and XPS, as well as BET analyses, were conducted for the Zinc–Cobalt bimetallic MOF structure. Subsequently, the properties attributed to the particles' active and barrier anti-corrosion feature in solution (NaCl) as well as coating (epoxy) phases were investigated. The EIS test performed in the solution phase, after 72h of metal exposure to Zn30-Z67 containing saline media, revealed a 590 % and 30 % increase in total resistance, respectively, compared to the uninhibited sample. Due to the increased stability of Zn10-Z67 in a saline environment, the active corrosion inhibition of the scratched coating containing these particles was increased by approximately 140 % compared to the Z67-containing composite. The incorporation of zinc cations into the structure of Z67 has enhanced the stability and control release features in aqueous environments, thereby enhancing the barrier properties of the epoxy coating. The reduction rate of log|Z|0.01Hz of the Zn10-Z67/EPC was 9 % which was lower than that of the Neat EPC (epoxy coating) (24 %).

Advanced 2D Computational Fluid Dynamics Model of an External Gear Pump Considering Relief Grooves

The article presents an advanced two-dimensional (2D) computational fluid dynamics (CFD) model of an external gear pump which considers relief grooves. Relief grooves are limiting design features for the flow process of this type of pump, and their influence in existing studies is considered by a three-dimensional (3D) model only. The structural modification proposed by the authors is beyond the possibilities of real implementation, but it gives the possibility to precisely model the pump’s design features. In contrast to the existing studies (using 3D CFD), the proposed advanced 2D model requires significantly fewer computing resources. Numerical experiments were carried out using the 2D model at different pump operating modes depending on the rotation frequency (950–1450 min−1) and pressure load (5–150 bar). The numerical results were validated by a real-world experiment for the same pump operating modes using an existing laboratory experimental setup. An analysis of the CFD model and real experiment results was carried out by determining a quantitative index of match (FIT), which varies in the range of 97.93–99.82%. This proves the performance of the proposed CFD model, which can be further used as a part of more complex hydraulic systems models.

Synthesis of DHDK Derivatives and Study of their Activity

AbstractDHDK is a novel diaryl heptanone analog isolated from mistletoe. (1 E, 4 E) 1,7‐bis (4‐hydroxyphenyl) hept‐1,4‐diene‐3‐one (DHDK) exhibits good antitumor activity and excellent stability, but it doesn't have good solubility or bioavailability. In order to improve this deficiency, the structure was modified and five new DHDK derivatives were successfully synthesized. The in vitro cytotoxic activity of DHDK derivatives against four cancer cell lines was determined by Cell Counting Kit‐8 (CCK‐8) assay. The results show that DHDK derivatives exhibit excellent potential, especially for human multiple myeloma cells (KMS‐11) and triple‐negative breast cancer cell line (MDA‐MB 231). The equilibrium solubility and oil‐water partition coefficient of DHDK derivatives were better improved by structural modification.

Progress Made in Non-Metallic-Doped Materials for Electrocatalytic Reduction in Ammonia Production

The electrocatalytic production of ammonia has garnered considerable interest as a potentially sustainable technology for ammonia synthesis. Recently, non-metallic-doped materials have emerged as promising electrochemical catalysts for this purpose. This paper presents a comprehensive review of the latest research on non-metallic-doped materials for electrocatalytic ammonia production. Researchers have engineered a variety of materials, doped with non-metals such as nitrogen (N), boron (B), phosphorus (P), and sulfur (S), into different forms and structures to enhance their electrocatalytic activity and selectivity. A comparison among different non-metallic dopants reveals their distinct effects on the electrocatalytic performance for ammonia production. For instance, N-doping has shown enhanced activity owing to the introduction of nitrogen vacancies (NVs) and improved charge transfer kinetics. B-doping has demonstrated improved selectivity and stability, which is attributed to the formation of active sites and the suppression of competing reactions. P-doping has exhibited increased ammonia generation rates and Faradaic efficiencies, likely due to the modification of the electronic structure and surface properties. S-doping has shown potential for enhancing electrocatalytic performance, although further investigations are needed to elucidate the underlying mechanisms. These comparisons provide valuable insights for researchers to conduct in-depth studies focusing on specific non-metallic dopants, exploring their unique properties, and optimizing their performance for electrocatalytic ammonia production. However, we consider it a priority to provide insight into the recent progress made in non-metal-doped materials and their potential for enabling long-term and efficient electrochemical ammonia production. Additionally, this paper discusses the synthetic procedures used to produce non-metal-doped materials and highlights the advantages and disadvantages of each method. It also provides an in-depth analysis of the electrochemical performance of these materials, including their Faradaic efficiencies, ammonia yield rate, and selectivity. It examines the challenges and prospects of developing non-metallic-doped materials for electrocatalytic ammonia production and suggests future research directions.

Exciton polaron formation and hot-carrier relaxation in rigid Dion-Jacobson-type two-dimensional perovskites.

The efficiency of two-dimensional Dion-Jacobson-type materials relies on the complex interplay between electronic and lattice dynamics; however, questions remain about the functional role of exciton-phonon interactions. Here we establish the robust polaronic nature of the excitons in these materials at room temperature by combining ultrafast spectroscopy and electronic structure calculations. We show that polaronic distortion is associated with low-frequency (30-60 cm-1) lead iodide octahedral lattice motions. More importantly, we discover how targeted ligand modification of this two-dimensional perovskite structure manipulates exciton-phonon coupling, exciton polaron population and carrier cooling. At high excitation density, stronger exciton-phonon coupling increases the hot-carrier lifetime, forming a hot-phonon bottleneck. Our study provides detailed insight into the exciton-phonon coupling and its role in carrier cooling in two-dimensional perovskites relevant for developing emerging hybrid semiconductor materials with tailored properties.

Short‐term effects of Kernza and alfalfa on microbial communities

AbstractContinuous land disturbance could negatively impact microbial community, but perennial crops can potentially reverse this negativity. The objective of this study was to evaluate the effects of Kernza (Thinopyrum intermedium) and alfalfa (Medicago sativa L.) on soil microbial structure and stress condition using the phospholipid fatty acid profiling. The study was conducted at the Ross Jones Research Farm, University of Missouri and consisted of four treatments: Kernza fertilized, Kernza unfertilized, Kernza and alfalfa intercrop, and alfalfa monocrop with four replications. Treatments were established in September 2021 on 18.3 m × 18.3 m plots. Soils from 0‐ to 5‐cm and 5‐ to 15‐cm depths were sampled in September 2021 (before treatments were placed) and 2022 and analyzed for microbial communities. All microbial communities increased after 1 year with the perennial crops. Since differences were not significant among treatments in 2022, this may lead to positive impacts of perennial crops on microbial communities, irrespective of the crop species and management. Moreover, community structure modifications were also observed with the perennial crops, irrespective of the species and management, as evidenced with changes in bacterial community indices in 2022. While fungi/bacteria ratio increased, Gram‐positive/Gram‐negative bacteria ratio decreased in 2022, suggesting a reduction in microbial stress, which can be attributed to ecological functions of the perennial crops. The study showed improvements in soil microbial biomass and modifications in microbial community structure after 1 year of Kernza and alfalfa. As the system matures, relative benefits of management (fertilization and intercropping) and plant species may be realized.

A synergistic combination of 2D MXene and MoO3 nanoparticles for improved gas sensing at room temperature

MXene Ti3C2T x (30% HF-etched, named Ti3C2T x -30) plays a pivotal role in the substantial enhancement of the structural modification of molybdenum trioxide (MoO3). Additionally, as the surface MoO3 molecules come into contact with reducing gas moieties, they actively participate in gas sensing at room temperature. The percentage of Ti3C2T x -30 in the MoO3 matrix was varied at 10%, 20%, and 40%, denoted as MM-10, MM-20, and MM-40, respectively. Structural analysis confirmed the composition of the basic elements and evolution of TiO2 at a higher percentage of Ti3C2T x -30. Spectroscopy analysis showed the interactions between Ti3C2T x -30 and MoO3, showcasing work functions of 6.91 eV, 6.75 eV, and 7.21 eV for MM-10, MM-20, and MM-40, respectively, confirming MM-20 to be an optimum composition. When the samples were exposed to ammonia gas, MM-20 showed a high response (93% for 100 ppm) at room temperature, with a response time of ∼10 s. Compared to bare MoO3, these samples showed ten-fold improvement. The excess electrons on the surface of Ti3C2T x -30 facilitate the formation of O2− species, which also provides stability to the otherwise highly reactive MXene surface. These species actively react with ammonia molecules in the presence of adsorbed MoO3, thereby changing the resistance of the system. This can be a significant step towards imparting high gas sensitivity to metal oxides at room temperature via incorporation of an optimum percentage of optimized Ti3C2T x .

Phase Transitions and Nonlinear Optical Property Modifications in BaGa4Se7.

Phase transitions can change the crystal structure and modify the physical properties of crystals. In this work, we investigate the phase transition behavior in BaGa4Se7, an important middle infrared (mid-IR) nonlinear optical (NLO) crystal, in the temperature range from room temperature to 1173 K. Interestingly, the BaGa4Se7 crystal undergoes a reversible ferroelastic phase transition at T = 528 K, resulting in the presence of a newly discovered phase (γ-phase) at the higher temperature. The experimental temperature dependence of optical birefringence, as well as the first-principles birefringence and NLO coefficients, reveals that the γ-phase exhibits larger birefringence and better NLO properties compared with those of the low-temperature phase (α-phase). This work demonstrates that phase-transition-induced structural modification can improve the mid-IR NLO properties, which would provide an effective avenue to obtain materials with good optoelectronic performance.

Isolation of anthraquinone derivatives from Rubia cordifolia (Rubiaceae) and their bioactivities against plant pathogenic microorganisms.

The discovery of antimicrobial ingredients from natural products could be an effective way to create novel fungicides. Rubia cordifolia L., a traditional Chinese herb, may have antimicrobial effects on plant pathogens according to our previous screening study. Rubia cordifolia L. extracts had moderate inhibitory effects on apple Valsa canker (Valsa mali) and tomato grey mould (Botrytis cinerea) at a concentration of 10 mg mL-1. With the use of bioguided isolation methods, eight compounds (1-8) were obtained, including the new compound 2,2,6-trimethyl-6-(4-methylphenyl)-tetrahydropyrano- 3-ol (7), and seven quinone derivatives. Two compounds, mollugin (1) and 1,3,6-trihydroxy-2-methylanthraquinone (6), were found to exhibit outstanding antifungal activities against V. mali and Phytophthora capsici Leon. The half maximal effective concentration (EC50) of compound 1 and compound 6 against V. mali were 79.08 and 81.78 μg mL-1, respectively, and the EC50 of compound 6 against P. capsici was 4.86 μg mL-1. Compound 1 also showed excellent activity against tobacco mosaic virus (TMV). The inactive, inductive, protective and curative activities against TMV were 84.29%, 83.38%, 86.81%, and 60.02%, respectively, at a concentration of 500 μg mL-1, which were all close to or greater than that of the positive control (100 μg mL-1 chitosan oligosaccharide, COS). Mollugin and 1,3,6-trihydroxy-2-methylanthraquinone are potentially valuable active compounds that lay a foundation for research on botanical fungicide products derived from R. cordifolia L. and provide lead structures for quinone derivative synthesis and structural modification. © 2024 Society of Chemical Industry.

Revolutionizing scandium detection in real samples: Unleashing the power of sol-gel-based optical sensor.

The development of a highly selective and ultra-sensitive optical sensor for detecting scandium (Sc3+) ions involves incorporating the reagent 2,3-dichloro-6-(3-carboxy-2-hydroxy-1-naphthylazo)quinoxaline (DCHNAQ) into a silica sol-gel thin film on a glass substrate. This innovative approach utilizes tetraethoxy-silane (TEOS) as the precursor, maintaining a sol-gel pH level of 4.5, a water-to-alkoxide ratio of 5:1, and a DCHNAQ concentration of 5.0 × 10-4M. A detailed exploration of the impact of sol-gel parameters on the sensing capabilities of the developed sensor has been meticulously undertaken. This innovative sensor demonstrates remarkable selectivity in evaluating Sc3+ ions over a dynamic range of 7.5-170ng/mL, with limits of quantification and detection recorded at 7.3 and 2.20ng/mL, respectively. Consistent results are achieved with a minimal RSD of 1.47 and 0.94% for Sc3+ ions at 50 and 100ng/mL, respectively, coupled with a swift response time of three min. Assessments of interference demonstrate a noteworthy preference for Sc3+ions, accomplished by enclosing DCHNAQ within the sol-gel framework and making optimal structural modifications to the doped sol-gel. The sensor offers straightforward regeneration using a 0.25M EDTA solution, exhibiting complete reversibility. Comparative analysis with other methodologies underscores the efficacy in determining Sc3+ions in various reference materials, including plant leaves, fish, water, alloys, ores, and monazite samples.

Porous Nanographenes, Graphene Nanoribbons, and Nanoporous Graphene Selectively Synthesized from the Same Molecular Precursor.

We demonstrate a family of molecular precursors based on 7,10-dibromo-triphenylenes that can selectively produce different varieties of atomically precise porous graphene nanomaterials through the use of different synthetic environments. Upon Yamamoto polymerization of these molecules in solution, the free rotations of the triphenylene units around the C-C bonds result in the formation of cyclotrimers in high yields. In contrast, in on-surface polymerization of the same molecules on Au(111) these rotations are impeded, and the coupling proceeds toward the formation of long polymer chains. These chains can then be converted to porous graphene nanoribbons (pGNRs) by annealing. Correspondingly, the solution-synthesized cyclotrimers can also be deposited onto Au(111) and converted into porous nanographenes (pNGs) via thermal treatment. Thus, both processes start with the same molecular precursor and end with a porous graphene nanomaterial on Au(111), but the type of product, pNG or pGNR, depends on the specific coupling approach. We also produced extended nanoporous graphenes (NPGs) through the lateral fusion of highly aligned pGNRs on Au(111) that were grown at high coverage. The pNGs can also be synthesized directly in solution by Scholl oxidative cyclodehydrogenation of cyclotrimers. We demonstrate the generality of this approach by synthesizing two varieties of 7,10-dibromo-triphenylenes that selectively produced six nanoporous products with different dimensionalities. The basic 7,10-dibromo-triphenylene monomer is amenable to structural modifications, potentially providing access to many new porous graphene nanomaterials. We show that by constructing different porous structures from the same building blocks, it is possible to tune the energy band gap in a wide range.

Synergistic exploration of antimicrobial potency, cytotoxicity, and molecular mechanisms: A tripartite investigation integrating in vitro, in vivo, and in silico approaches for pyrimidine‐based metal (II) complexes

We synthesized and characterized bioactive metal (II) complexes from a pyrimidine‐based Schiff base ligand, 4‐[2‐(4‐chlorobenzylidene) hydrazinyl]‐7H‐pyrrolo[2,3‐d]pyrimidine. Through thorough elemental analysis and various physicochemical techniques, we characterized both the ligand and its Zn(II), Cd(II), and Hg(II) complexes. Coordination of the metallic ion was established via nitrogen atoms from the ligand's pyrrolo and pyrimidine rings, yielding tetrahedral complexes of the type [M(PPHpCB)2]. These complexes are identified as non‐electrolytes due to their low molar conductance. Furthermore, we investigated the coordination behavior of the pyrimidine‐based Schiff base ligand (HPPHpCB) with metal ions through comprehensive spectroscopic analysis. 1H NMR spectral data showed bonding between HPPHpCB and metal ions, while UV spectra confirmed intra‐ligand and ligand‐to‐metal charge transfer transitions, indicating coordination through nitrogen atoms. The determination of tetrahedral geometry for metal complexes confirmed their diamagnetic properties. Analysis using 13C NMR and electrospray ionization mass spectra (ESI‐MS) revealed variations in chemical shifts, confirming successful complex formation and elucidating structural modifications, electronic interactions, and metal–ligand coordination modes. Moreover, evaluation of in vitro antimicrobial activities using the minimum inhibitory concentration (MIC) approach revealed significant antibacterial and antifungal activities for Hg(II) and Cd(II) complexes, respectively. The Hg(II) complex displayed superior antioxidant activity, while Zn(II) and Cd(II) complexes also demonstrated considerable potential. In vivo, cytotoxicity assessments against Artemia salina provided insights into the cytotoxic properties of ligands and metal complexes. Computational techniques suggested their potential in combating infectious ailments. Overall, our study establishes the synthesis, characterization, and multifaceted biological activities of metal (II) complexes derived from the pyrimidine‐based Schiff base ligand, highlighting their promising role in combating various infectious diseases.

The Miraculous of Rhizopus arrhizus in the Structural Modifications of Steroidal Skeleton

Abstract: Many natural and synthetic steroidal compounds have been converted by biotransformation to get highly valuable products for pharmaceuticals or chemical intermediates for the production of drugs. This review summarizes the biotransformation of sixty-six steroids1-66 (ten of pregnane 1-10, fifty of androstane 11-60 while six steroids of estrane series 61-66) by using different strains of Rhizopus arrhizus, a well-known fungus of the zygomycetes group, used in food, dairy, pharmaceutical and numerous biotechnological processes. R. arrhizus transformed only fifty-four compounds 1-51 and 61-63, whereas nine compounds of androstane 52-60 and three compounds of estrane series 64-66 remained unchanged. R. arrhizus brought various structural modifications in steroids, including hydroxylation, epoxidation, epoxide hydrolysis, reduction of double bonds and ketonic group, dechlorination and defluorination, deacetylation, oxidation of various functional groups and isomerization.

Single-cell 3D genome structure reveals distinct human pluripotent states

BackgroundPluripotent states of embryonic stem cells (ESCs) with distinct transcriptional profiles affect ESC differentiative capacity and therapeutic potential. Although single-cell RNA sequencing has revealed additional subpopulations and specific features of naive and primed human pluripotent stem cells (hPSCs), the underlying mechanisms that regulate their specific transcription and that control their pluripotent states remain elusive.ResultsBy single-cell analysis of high-resolution, three-dimensional (3D) genomic structure, we herein demonstrate that remodeling of genomic structure is highly associated with the pluripotent states of human ESCs (hESCs). The naive pluripotent state is featured with specialized 3D genomic structures and clear chromatin compartmentalization that is distinct from the primed state. The naive pluripotent state is achieved by remodeling the active euchromatin compartment and reducing chromatin interactions at the nuclear center. This unique genomic organization is linked to enhanced chromatin accessibility on enhancers and elevated expression levels of naive pluripotent genes localized to this region. In contradistinction, the primed state exhibits intermingled genomic organization. Moreover, active euchromatin and primed pluripotent genes are distributed at the nuclear periphery, while repressive heterochromatin is densely concentrated at the nuclear center, reducing chromatin accessibility and the transcription of naive genes.ConclusionsOur data provide insights into the chromatin structure of ESCs in their naive and primed states, and we identify specific patterns of modifications in transcription and chromatin structure that might explain the genes that are differentially expressed between naive and primed hESCs. Thus, the inversion or relocation of heterochromatin to euchromatin via compartmentalization is related to the regulation of chromatin accessibility, thereby defining pluripotent states and cellular identity.

Cardiovascular and physiological risk factors in women at midlife and beyond.

Cardiovascular disease (CVD) is the leading cause of death in women. After menopause, sex-specific and gender-specific factors may play an important role in increasing CVD risk, with changes in sex hormones, body fat distribution, lipid and metabolic profile, and structural and functional vascular modifications. Premature and early-onset menopause are detrimental to cardiovascular health due to the early cessation of the protective effect of endogenous estrogen. An independent association of menopause with an increased risk of CVD has been documented in early menopause (<45 years). Sex-related differences are relevant in pharmacokinetics and pharmacodynamics; different enzyme formations, drug compatibility, efficacy, and side effects vary for different sexes. Despite some progress in sex and gender research in CVD, disparities remain. Menopausal hormone therapy (MHT) is available at midlife for symptoms of menopause and may impact CVD risk. Taken early, MHT may reduce CVD morbimortality. However, this is balanced againts the risk of increased thrombosis. This paper reviews physiologic changes that contribute to cardiovascular risk in postmenopausal women and discusses clinical implications. Specifically, it explores the atheroprotective effects of estrogen and menopausal hormone therapy and the associations between menopause with lipid levels, hypertension, body composition, and diabetes for women at midlife and beyond.