16α-Hydroxycleroda-3,13(14)Z-dien-15,16-olide (4655K-09 or K-09) is a novel clerodane diterpene lactone reported for its anti-hyperlipidemic efficacy. The objective of the present study was to ...investigate the probable reversible metabolism of 4655K-09 and evaluate its effects on pharmacokinetic (PK) properties.
The PK studies were carried out through intravenous (IV) bolus administration of 4655K-09 and K-9T in mice at a dose of 3, 6 and 12 mg/kg separately. The oral PK study of 4655K-09 was carried out at therapeutic dose of 25 mg/kg.
The % AUC of metabolite converted to parent upon its administration
was found to be 27.28 ± 2.67. The multi-compartmental interconversion model defined reversible and irreversible clearances along with volumes of distribution for parent and metabolite. The results emphasized that hydrolysis of lactone to acid was more efficient than back conversion to parent due to greater extent of irreversible elimination of acid. Further, the role of interconversion in pharmacokinetics of 4655K-09 was evaluated through secondary parameters like conversion coefficients of parent to metabolite (
), metabolite to parent (
: 0.019 ± 0.001), exposure enhancement (EE: 1.04 ± 0.006), and recycled fraction (RF: 0.042 ± 0.007), highlighted the minimal role of interconversion. The estimation of oral bioavailability remains unaffected when calculated through considering reversible metabolism.
The present model-based interconversion pharmacokinetics of 4655K-09 in mice could be further extended to other species to support its development as anti-hyperlipidemic agent.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
We experimentally investigate the charge-spin interconversion by introducing a lighter impurity, namely nitrogen (N) into Pt by varying the nitrogen gas flow rate,
from 0 to 20%, and studying the ...Onsager reciprocity of spin Hall effect (SHE) via complementary methods of spin-torque ferromagnetic resonance and spin-pumping inverse SHE measurements, respectively. We notice a reduction in the crystalline nature of Pt upon nitrogen incorporation. We observe the influence of extrinsic side-jump scattering induced SHE by measuring the spin Hall efficiency,θSHin a wide temperature range from 10 to 296 K. This work establishes the incorporation of N in Pt by using sputtering, to enhance the SHE via extrinsic scattering as well as to observe the reciprocal effects of charge-spin interconversion.
A novel structural interconversion unit based on intramolecular boroxine formation has been developed. The interconversion of a macrocyclic triboronic acid (blue Japanese umbrella) and a tricyclic ...boroxine (green pinwheel) can be triggered by water or temperature. These unique interconversions are attributed to the entropic advantage of intramolecular boroxine formation. More information can be found in the Research Article by K. Ono and co‐workers (DOI: 10.1002/chem.202300995).
A charge density wave (CDW) represents an exotic state in which electrons are arranged in a long‐range ordered pattern in low‐dimensional materials. Although the understanding of the fundamental ...character of CDW is enriched after extensive studies, its practical application remains limited. Here, an unprecedented demonstration of a tunable charge‐spin interconversion (CSI) in graphene/1T‐TaS2 van der Waals heterostructures is shown by manipulating the distinct CDW phases in 1T‐TaS2. Whereas CSI from spins polarized in all three directions is observed in the heterostructure when the CDW phase does not show commensurability, the output of one of the components disappears, and the other two are enhanced when the CDW phase becomes commensurate. The experimental observation is supported by first‐principles calculations, which evidence that chiral CDW multidomains in the heterostructure are at the origin of the switching of CSI. The results uncover a new approach for on‐demand CSI in low‐dimensional systems, paving the way for advanced spin‐orbitronic devices.
An unprecedented tunable charge‐spin interconversion (CSI) is observed in graphene/1T‐TaS2 van der Waals heterostructures by manipulating the charge density wave (CDW) phases in 1T‐TaS2. The output of one of the CSI components switches off with the commensurability of the CDW phases. First‐principles calculations support that chiral CDW multidomains in the heterostructure are at the origin of the switching of CSI.
The mutual oxidation of n-pentane and NO2 at 500–1000 K has been studied at equivalence ratios of 0.5 and 1.33 by using an atmospheric-pressure jet stirred reactor (JSR). N-pentane, O2, NO, NO2, CO, ...CO2, CH2O, C2H4, and CH3CHO are simultaneously quantified, in-situ by using an electron-impact molecular beam mass spectrometer (EI-MBMS), a micro-gas chromatograph (μ-GC), and a mid-IR dual-modulation faraday rotation spectrometer (DM-FRS). Both fuel lean and rich experiments show that, in 550–650 K, NO2 addition inhibits low temperature oxidation. With an increase of temperature to the negative temperature coefficient (NTC) region (650–750 K), NO2 addition weakens the NTC behavior. In 750–1000 K, high temperature oxidation is accelerated with NO2 addition and shifted to lower temperature. Two kinetic models, a newly developed RMG n-pentane/NOx model and Zhao's n-pentane/NOx model (Zhao et al., 2018, Submitted) were validated against experimental data. Both models were able to capture the temperature-dependent NO2 sensitization characteristics successfully. The results show that although NO2 addition in n-pentane has similar effects to NO at many conditions due to fast NO and NO2 interconversion at higher temperature, it affects low temperature oxidation somewhat differently. When NO2/NO interconversion is slow, NO2 is relatively inert while NO can strongly promote or inhibit oxidation.
•NO2 shows three temperature dependent effects on n-pentane oxidation.•When NO2/NO interconversion is slow, NO2 is relatively inert on the oxidation.•NO2 and NO have similar sensitization effects at fast NO2/NO interconversion.•Reactions RO2 = QOOH, RO2+NO = RO + NO2, and RO2+M = C5H10+HO2+M explain the NO2 effects.
Enzymatic cascade reactions experience tremendous attention by cutting short conventional step-by-step synthesis in a highly efficient and elegant fashion. Focusing on ω-transaminases, this review ...provides an overview of different biocatalytic strategies to afford a variety of (chiral) amines employing diverse cascade systems: Cascades to shift the reaction equilibrium as well as cascades for the amination of alcohols and nonactivated C–H bonds are discussed. Cascades enable the deracemization of rac-amines, other ones involve biocatalyzed C–C bond formation and C–C bond hydrolysis. Finally, the potential of spontaneous ring closure reactions initiated by ω-transaminases is illustrated.
Due to the increasing demand for propylene, highly selective propylene production from ethylene using small pore zeolite has received significant attention. However, rapid catalyst deactivation due ...to coke deposition on the catalyst impedes effective propylene production in industry. Therefore, it is essential to develop a low-temperature regeneration ethylene-to-propylene (ETP) catalyst with stable catalytic activity. To achieve such a catalyst, various hydrocracking metal species and phosphorus-supported SSZ-13 were prepared and evaluated using a one-pass ETP and ETP-Regen test. The optimized catalyst NiO(1.0)-P(0.6)-SSZ-13 exhibited a constant, excellent propylene yield of over 70 wt% with 90 wt% of propylene selectivity over ETP reaction and consecutive ETP-Regen cycles. The unprecedented catalytic performance of NiO(1.0)-P(0.6)-SSZ-13 was ascribed to the synergistic effect of NiO and P components, where nickel is responsible for catalyst recovery through effective coke removal, while phosphorus plays an essential role in size-selective diffusion.
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•Reducing the temperature gap between the ETP reaction and regeneration.•High Max. propylene yield (> 70 wt%) is well preserved over multiple ETP-Regen cycles using NiO-P-SSZ-13 catalyst.•The synergistic role of NiO and P in the NiO-P-SSZ-13 was elucidated.•Ni, P loading on H-SSZ-13 and ETP-Regen conditions were optimized.•Effective and selective coke hydrocracking was explained via the alkyl naphthalene-base hydrocarbon pool mechanism.
The intestinal epithelium is a rapidly renewing cellular compartment. This constant regeneration is a hallmark of intestinal homeostasis and requires a tightly regulated balance between intestinal ...stem cell (ISC) proliferation and differentiation. Since intestinal epithelial cells directly contact pathogenic environmental factors that continuously challenge their integrity, ISCs must also actively divide to facilitate regeneration and repair. Understanding niche adaptations that maintain ISC activity during homeostatic renewal and injury-induced intestinal regeneration is therefore a major and ongoing focus for stem cell biology. Here, we review recent concepts and propose an active interconversion of the ISC niche between homeostasis and injury-adaptive states that is superimposed upon an equally dynamic equilibrium between active and reserve ISC populations.
The homeostatic niche maintains the activity of Lgr5+ intestinal stem cells and the relative quiescence of reserve ISCs.
Upon injury, the ISC niche undergoes substantial adaptation to effect epithelial repair, potentially by activating reserve ISC populations.
The intestinal stroma, epithelium, and paracrine signals may all underlie niche adaptations to injury.
Microbes, viruses, diet, and inflammation are external factors that impact the integrity of ISCs, thus affecting intestinal epithelial health in homeostasis and influencing recovery upon injury.
Silver–acetylene interactions adopting a heteroleptic ternary coordination mode enabled the synthesis of concave polyhedral cages upon anion‐exchange‐triggered interconversion of highly entangled ...polyhedra. In their Communication (e202303714), Yuya Domoto and co‐workers describe skeletally edited 3D architectures having partially disconnected knot or link motifs at their polyhedral faces.
The relative conformer energies of glycine are evaluated by using a focal point analysis expressed as ( HF → MP 2 → MP 3 → CCSD → CCSD ( T ) ). The conformer abundances at various temperatures ...(298−500 K) are calculated based on the relative energies and Boltzmann statistical thermostatistical analysis with and without considering internal hindered rotations. A comparison between the available Raman spectrum and the electron momentum spectrum confirms that the influence of rigid-rotor hindered rotation on the conformational proportions of glycine is considerable, especially for the IIIp structure. The conformational interconversions are discussed. It is found that with increasing temperature, the mole fraction of IIn keeps constant and Ip structure can convert into IVn and IIIp, leading to the decrease in the weight of Ip and the increase in the weights of IVn and IIIp conformers, which is in accordance with experimental observations.
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