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Background: Colony‐stimulating factor 1 receptor (CSF1R)‐related disorder (CRD) is a rare autosomal dominant disease. The clinical and genetic characteristics of Chinese patients have not been elucidated. Objective: The objective of the study is to clarify the core features and influence factors of CRD patients in China. Methods: Clinical and genetic‐related data of CRD patients in China were collected. Mini‐Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Sundal MRI Severity Score were evaluated. Whole exome sequencing was used to analyze the CSF1R mutation status. Patients were compared between different sexes, mutation types, or mutation locations. Results: A total of 103 patients were included, with a male‐to‐female ratio of 1:1.51. The average age of onset was (40.75 ± 8.58). Cognitive impairment (85.1%, 86/101) and parkinsonism (76.2%, 77/101) were the main clinical symptoms. The most common imaging feature was bilateral asymmetric white matter changes (100.0%). A total of 66 CSF1R gene mutants (22 novel mutations) were found, and 15 of 92 probands carried c.2381 T > C/p.I794T (16.30%). The MMSE and MoCA scores (17.0 [9.0], 11.90 ± 7.16) of female patients were significantly lower than those of male patients (23.0 [10.0], 16.36 ± 7.89), and the white matter severity score (20.19 ± 8.47) of female patients was significantly higher than that of male patients (16.00 ± 7.62). There is no statistical difference in age of onset between male and female patients. Conclusions: The core manifestations of Chinese CRD patients are progressive cognitive decline, parkinsonism, and bilateral asymmetric white matter changes. Compared to men, women have more severe cognitive impairment and imaging changes. c.2381 T > C/p.I794T is a hotspot mutation in Chinese patients. © 2024 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Aim: To assess the safety, tolerability, pharmacokinetics (PKs) and pharmacodynamics of HRS‐7535, a novel glucagon‐like peptide‐1 receptor agonist (GLP‐1RA), in healthy participants. Materials and Methods: This phase 1 trial consisted of single‐ascending dose (SAD), food effect (FE) and multiple‐ascending dose (MAD) parts. In the SAD part, participants were randomized (6:2) to receive HRS‐7535 (at doses of 15, 60 and 120 mg; administered orally once daily) or placebo. In the FE part, participants were randomized (8:2) to receive a single dose of 90‐mg HRS‐7535 or placebo, in both fed and fasted states. In the MAD part, participants were randomized (18:6) to receive daily HRS‐7535 (120 mg [30/60/90/120‐mg titration scheme]) or placebo for 28 days. The primary endpoints were safety and tolerability. Results: Nausea and vomiting were the most frequently reported AEs across all three parts. In the SAD part, the median Tmax was 5.98‐5.99 hours and the geometric mean t1/2 was 5.28‐9.08 hours across the HRS‐7535 dosing range. In the MAD part, the median Tmax was 5.98‐10.98 hours and the geometric mean t1/2 was 6.48‐8.42 hours on day 28 in participants on HRS‐7535. PKs were approximately dose‐proportional. On day 29 in the MAD part, the mean (percentage) reduction in body weight from baseline was 4.38 kg (6.63%) for participants who received HRS‐7535, compared with 0.8 kg (1.18%) for those participants who received a placebo. Conclusions: HRS‐7535 exhibited a safety and tolerability profile consistent with other GLP‐1RAs and showed PKs suitable for once‐daily dosing. These findings support further clinical development of HRS‐7535 for type 2 diabetes. [ABSTRACT FROM AUTHOR]

HY072808 is a novel phosphodiesterase 4 inhibitor currently under clinical development to treat atopic dermatitis. The first step is to address the pharmacokinetics and safety after topical administration of HY072808 ointments in healthy humans. In this study, we developed a highly sensitive liquid chromatography–tandem mass spectrometry method to determine plasma HY072808 and its active metabolite, ZZ24, in tiny amounts. The plasma samples were prepared using a simple liquid–liquid extraction method. Liquid chromatographic separation was achieved by gradient elution. The MS/MS quantification was performed in positive ion mode via multiple reaction monitoring. The method showed satisfactory linearity from 10 to 4,000 pg/ml for HY072808 and ZZ24. There was no significant interference from blank plasma. The method was validated for accuracy and precision, matrix effect and extraction recovery, dilution integrity, injection carryover and stability according to the related guidelines of the regulatory authorities. The HY072808 and ZZ24 concentrations in human plasma from a clinical trial were determined using this method. In conclusion, the validated method was robust and could be utilized to support the clinical development of HY072808. [ABSTRACT FROM AUTHOR]

The purpose of this paper is to explore the current research status, hot topics, and future prospects in the field of graphene and its derivatives toxicity. In the article, the Web of Science Core Collection database was used as the data source, and the CiteSpace and VOSviewer were used to conduct a visual analysis of the last 10 years of research on graphene and its derivatives toxicity. A total of 8573 articles were included, and we analyzed the literature characteristics of the research results in the field of graphene and its derivatives toxicity, as well as the distribution of authors and co‐cited authors; the distribution of countries and institutions; the situation of co‐cited references; and the distribution of journals and categories. The most prolific countries, institutions, journals, and authors are China, the Chinese Academy of Sciences, RSC Advances, and Wang, Dayong, respectively. The co‐cited author with the most citations was Akhavan, Omid. The five research hotspot keywords in the field of graphene and its derivatives toxicity were "nanomaterials," "exposure," "biocompatibility," "adsorption," and "detection." Frontier topics were "facile synthesis," "antibacterial activity," and "carbon dots." Our study provides perspectives for the study of graphene and its derivatives toxicity and yields valuable information and suggestions for the development of graphene and its derivatives toxicity research in the future. The purpose of this paper is to explore the current research status, hot topics, and future prospects in the field of graphene and its derivatives toxicity. In the article, the Web of Science Core Collection database was used as the data source, and the CiteSpace and VOSviewer were used to conduct a visual analysis of the last 10 years of research on graphene and its derivatives toxicity. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusion More than 60% of paroxysmal kinesigenic dyskinesia (PKD) cases are of uncertain variants.The aim was to elucidate novel genetic contribution to PKD.A total of 476 probands with uncertain genetic causes were enrolled for whole‐exome sequencing. A method of case–control analysis was applied to identify the candidate genes. Whole‐cell patch‐clamp recording was applied to verify the electrophysiological impact of the identified variants. A mouse model with cerebellar heterozygous knockout of the candidate gene was developed via adeno‐associated virus injection, and dystonia‐like phenotype inducement and rotarod tests were performed. In vivo multiunit electrical recording was applied to investigate the change in neural excitability in knockout mice.Heterozygous variants of potassium inwardly rectifying channel subfamily J member 10 (KCNJ10) clustered in PKD patients were compared with those in the control groups. Fifteen variants were detected in 16 of 522 probands (frequency = 3.07%). Patients with KCNJ10 variants tended to have a milder manifestation compared to those with PRRT2 (proline‐rich transmembrane protein 2) variants. KCNJ10 variants partially altered the transmembrane location of inwardly rectifying potassium channel 4.1 (Kir4.1). The Kcnj10 expression is consistent with the natural course of PKD. Variants resulted in different degrees of reduction in cell Kir4.1 currents, and mice with heterozygous conditional knockout of Kcnj10 in the cerebellum presented dystonic posture, together with poor motor coordination and motor learning ability in rotarod tests. The firing rate of deep cerebellar nuclei was significantly elevated in Kcnj10‐cKO mice.We identified heterozygous variants of KCNJ10 in PKD. Impaired function of Kir4.1 might lead to abnormal neuronal excitability, which attributed to PKD. © 2024 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

The excellent functionalities of perovskite oxides and the growing demands for flexible devices lead to great interests on epitaxial growth of functional oxide films on flexible mica substrates. Understanding the film epitaxy on the substrate with a very different crystal structure is a key issue for the optimization of the film growth and hence properties. Such understanding largely depends on knowing the atomic structure of the interfaces between the films and the substrates. Here, the interface between the epitaxial films of SrTiO3 on the fluorophlogopite mica substrate is studied in detail. Two types of interfaces, clean or with secondary phase, exist in this system, leading to two types of crystallographic orientation relationships. Atomic‐resolution scanning transmission electron microscopy images reveal that at the clean interface the (111) Sr–O3 atomic plane of SrTiO3 interacts with the (001) (SiAl)2–O3 plane of mica. This interface structure and thus the epitaxy of the film are understood in light of the strong similarity of the oxygen sublattices in these two atomic planes. First‐principles calculations demonstrate strong bonding of the atoms at the interface, which is also corroborated by the observation of misfit dislocations at the interfaces. [ABSTRACT FROM AUTHOR]