Pressure‐Driven Reactivity in Dense Methane‐Nitrogen Mixtures

Abstract Carbon, nitrogen, and hydrogen are among the most abundant elements in the solar system, and our understanding of their interactions is fundamental to prebiotic chemistry. CH 4 and N 2 are the simplest archetypical molecules formed by these elements and are both markedly stable under extremes of pressure. Through a series of diamond anvil cell experiments supported by density functional theory calculations, we observe diverse compound formation and reactivity in the CH 4 ‐N 2 binary system at high pressure. Above 7 GPa two concentration‐dependent molecular compounds emerge, (CH 4 ) 5 N 2 and (CH 4 ) 7 (N 2 ) 8 , held together by weak van der Waals interactions. Strikingly, further compression at room temperature irreversibly breaks the N 2 triple bond, inducing the dissociation of CH 4 above 140 GPa, with the near‐quenched samples revealing distinct spectroscopic signatures of strong covalently bonded C−N−H networks. High temperatures vastly reduce the required pressure to promote the reactivity between CH 4 and N 2 , with NH 3 forming together with longer‐chain hydrocarbons at 14 GPa and 670 K, further decomposing into powdered diamond when temperatures exceed 1200 K. These results exemplify how pressure‐driven chemistry can cause unexpected complexity in the most simple molecular precursors.

Engineering a Meltable MOF to Tune Liquid Transition and Promote Coenzyme Regeneration

Abstract Modulating the liquid phase of metal–organic frameworks (MOFs) presents new opportunities for functionalizing glassy MOFs, expanding the fundamental science and practical application for this emerging family of materials. Herein, we report the fabrication of a bimetallic glassy MOF via a liquid–liquid transition process. This is achieved by introducing a robust Schiff base–cobalt functional group into Zn‐ZIF‐62, which attracts negatively charged imidazolate ligands, facilitating low‐temperature melting. This ultimately leads to the formation of a bimetallic glassy MOF (Co/Zn‐a g ZIF‐62‐ipy) upon melt‐quenching. The material features an exceptionally high glass‐forming capability, uniformly distributed bimetallic ions, and a markedly enhanced visible light photogeneration efficiency of enzymatically active nicotinamide adenine dinucleotide (NADH) when compared with Co‐doped ZIF‐62 glass. These findings offer novel insights into modulating the liquid phase of an MOF to develop functional glassy MOF photocatalysts for coenzyme NADH regeneration and other advanced applications.

Outside Back Cover: Engineering a Meltable MOF to Tune Liquid Transition and Promote Coenzyme Regeneration (Angew. Chem. Int. Ed. 32/2025)

In their Research Article ( e202506570 ), Jingwei Hou, Wengang Huang and co‐workers developed a bimetallic MOF glass (Co/Zn‐agZIF‐62‐ipy) via a liquid–liquid transition, incorporating Schiff base–Co units. The resulting glass shows high glass‐forming ability, uniform metal dispersion, and enhanced visible‐light‐driven NADH regeneration. This work presents a novel strategy to tune MOF liquid phases for stable, non‐noble metal photocatalysts mimicking enzymatic function.

N ‐[4‐(Benzyloxy)‐3‐methoxybenzyl)]adamantane‐1‐amine (DZH2), a dual CCR5 and CXCR4 inhibitor as a potential agent against triple negative breast cancer

Abstract DZH2, a dual inhibitor of the chemokine receptors CCR5 and CXCR4, was discovered from virtual screening for CCR5 antagonists. In specific Ca 2+ chemokine signaling assays, DZH2 displayed low micromolar IC 50 values at both chemokine receptors. Its binding to intracellular allosteric binding sites of CCR5 and CXCR4 was confirmed by MD simulations and binding free‐energy calculations. DZH2 is superior to the CCR5 antagonist maraviroc in terms of its inhibitory activity on the growth of two breast cancer cell lines. In MCF7 and MDA‐MB‐231 cells, DZH2 was a >100‐fold more potent inhibitor of cell viability compared to maraviroc. DZH2 (6.7 µM) reduced migration of MDA‐MB‐231 cells to 4% compared to 50% inhibition of migration caused by maraviroc (780 µM). Also, DZH2 was a significantly more potent inhibitor of colony formation in MDA‐MB‐231 cells than maraviroc. In MCF10 cells, DZH2 caused no alteration in the gene expression with respect to cellular pathways mediating cell death, indicating its selectivity to breast cancer cells.

New Anti‐HIV Agents Isolated From Two Euphorbia Species

ABSTRACT Four previously unreported tigliane diterpenes ( 1 , 2 , 4 , and 6 ), along with two known tiglianes ( 3 and 5 ), were isolated from the latex of Euphorbia palustris and Euphorbia lucida . The structures of the isolated compounds were elucidated by spectroscopic techniques. Antiviral activity assays for compounds 1 ‒ 4 and 6 against HIV‐1 and HIV‐2 replication were performed on a CD4 + T cell line, MT‐4 cells. The compounds were tested for their ability to inhibit infection by the HIV‐1 strain NL4.3 and the HIV‐2 strain ROD. Compound 6 showed no activity against either strain, while compound 4 was only slightly active against HIV‐2 (EC 50  = 12.778 µM). Compounds 1 , 2 , and 3 were able to inhibit both HIV‐1 and HIV‐2 infections. Among them, compound 2 was the most potent, with EC 50 values of 0.069 µM for HIV‐1 NL4.3 and 0.023 µM for HIV‐2 ROD. The PBMC toxicity profile for compound 2 is also more favorable compared with MT‐4 cells with CC 50  = 50 μM.

Development and Validation of a LC‐MS/MS Method for Ripretinib and Its Metabolite: Example of a Journey From Laboratory Bench to Routine Application With a Greenness Assessment

ABSTRACT Therapeutic drug monitoring of protein kinase inhibitors is widely practiced worldwide. Based on the example of ripretinib dosage requested by a clinician, we detailed the process of method development, using a literature‐based approach while ensuring the sustainability of the method to be as environmentally friendly as possible. Therefore, a UPLC‐MS/MS method for ripretinib and its active metabolite was optimized and validated using the corresponding stable isotopic internal standards in human plasma. The procedure employed a mobile phase mixture of water with 1% acetic acid and 0.1% formic acid, and acetonitrile. Positive electrospray ionization was performed, coupling with multiple reaction monitoring of m / z 510.4 → 417.4 and 510.4 → 389.4 for ripretinib, and 496.3 → 403.3 and 496.3 → 375.3 for N ‐desmethyl‐ripretinib. The method was successfully validated according to the current version of the ICH Guideline provided by the EMA. The greenness assessment score of this procedure was better than previously published approaches using the AGREE metric. The validated UPLC‐MS/MS method successfully monitored ripretinib and its metabolite concentrations in clinical and preclinical models.

Cerebral Venous Thrombosis and Nitrous Oxide Intoxication: Report of Two Cases and Review of the Literature

ABSTRACT Background Cerebral venous thrombosis (CVT) has various risk factors, including contraception, pregnancy, neoplasia, and thrombophilia. Nitrous oxide (N₂O), historically used as an anesthetic and more recently as a recreational drug, has been associated with neurological complications such as myeloneuropathy and thromboembolic events. Here, we report two cases of CVT associated with N₂O use and provide a review of the literature on this association. Methods We describe two local cases of CVT associated with N 2 O use and 10 additional cases identified by literature review. Results Among the 12 patients, seven had co‐existing CVT risk factors. Most patients reported chronic N 2 O use. Hyperhomocysteinemia was reported in nine patients. Management included anticoagulation, vitamin supplementation, cessation of N₂O use, and support for addiction or psychiatric care. The outcome was generally favorable, although one local case experienced CVT recurrence following a relapse in N₂O use. Conclusions These cases highlight an emerging association between CVT and N₂O use. Prompt recognition of this link is critical to recommend cessation of N₂O use, alongside anticoagulation therapy and consideration of vitamin supplementation to prevent complications and recurrence.

Effects of a Valerian‐Hops Extract Combination (Ze 91019) on Sleep Duration and Daytime Cognitive and Psychological Parameters in Occasional Insomnia: A Randomized Controlled Feasibility Trial

ABSTRACT Objective/Background This study evaluated the feasibility of investigating the effect of a valerian and hops‐based herbal medication (Ze 91019) on daytime cognitive performance, psychological parameters, and sleep measures in individuals with occasional sleep problems. Methods A randomized, double‐blind, placebo‐controlled study was conducted in 40 participants over a 21‐day run‐in period and a 21‐day treatment period. Participants used Fitbit sleep trackers and completed daily online cognitive tests (i.e., reaction time and working memory), and surveys to assess subjective psychological outcomes (i.e., cognitive performance, stress levels, tiredness, mood, quality of life, and motivation). Results The study design proved feasible, with high adherence to the study protocol. Exploratory analyses revealed a statistically significant increase in sleep duration during the treatment period for participants using Ze 91019 compared to placebo (mean daily increase: 21.7 min, p = 0.019) without statistically significant effects on cognitive or psychological outcomes. Moreover, Ze 91019 statistically significantly increased the sleep duration of the shortest night in the treatment period by 48.7 minutes. The medication was well‐tolerated. Conclusions The study design proved feasible, and Ze 91019 increased sleep duration without affecting daytime cognitive or psychological outcomes. Trial Registration The trial has been preregistered at www.clinicaltrials.gov (NCT05684523).

Upper end of the central canal of the human spinal cord: Quantitative anatomical study and 3D modeling

Abstract The upper end of the central canal of the human spinal cord has been repeatedly implicated in the pathogenesis of various diseases, yet its precise normal position in the medulla oblongata and upper cervical spinal cord remains unclear. The purpose of this study is to describe the anatomy of the upper end of the central canal with quantitative measurements and a three‐dimensional (3D) model. Seven formalin‐embalmed human brainstems were included, and the central canal was identified in serial axial histological sections using epithelial membrane antigen antibody staining. Measurements included the distances between the central canal (CC) and the anterior medullary fissure (AMF) and the posterior medullary sulcus (PMS). The surface and perimeter of the CC and the spinal cord were calculated, and its anterior–posterior and maximum lateral lengths were measured for 3D modeling. The upper end of the CC was identified in six specimens, extending from the apertura canalis centralis (ACC) to its final position in the cervical cord. Positioned on the midline, it reaches its final location approximately 15 mm below the obex. No specimen showed canal dilatation, focal stenosis, or evidence of syringomyelia. At 21 mm under the ACC in the cervical cord, the median distance from the CC to the AMF was 3.14 (2.54–3.15) mm and from the CC to the PMS was 5.19 (4.52–5.43) mm, with a progressive shift from the posterior limit to the anterior third of the cervical spinal cord. The median area of the CC was consistently less than 0.1 mm 2 . The upper end of the CC originates at the ACC, in the posterior part of the MO, and reaches its normal position in the anterior third of the cervical spinal cord less than 2 cm below the obex. Establishing the normal position of the upper end of this canal is crucial for understanding its possible involvement in cranio‐cervical junction pathologies.

Targeting ferroptosis resistance resensitizes metastatic HR + HER2 − breast cancer cells to palbociclib‐hormone therapy