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Objective·To summarize and analyze the clinical and genetic characteristics of adult cerebral adrenoleukodystrophy(ACALD ).Methods·The data of eight patients with ACALD who attended the Shanghai Sixth People′s Hospital, Shanghai Jiao Tong University School of Medicine from June 2018 to September 2022 were collected and comprehensively analyzed. Clinical data included age at onset, duration of disease, family history, present history and physical examination. Imaging examinations included magnetic resonance imaging (MRI) of the cranial, cervical spine and thoracic spine. Laboratory tests included serum very-long-chain fatty acids (VLCFA), adrenal cortical function and genetic test. Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (Moca) were used to assess patients′ cognitive function.Results·A total of 8 male patients with ACALD were included in this study. Ageat onset ranged from 23 to 40 years old with an average age of (32.75±5.80) years, and the disease duration ranged from 4 to 59 months. Patients′ first symptoms were highly variable. Three patients showed memory loss and cognitive dysfunction, two showed irritability and personality change, one showed mental and behavioral abnormalities, one showed dysarthria and ataxia, and one showed persistent dizziness, occipital numbness and insomnia. All the patients had multiple white matter demyelination lesions, and white matter demyelination in parietal occipital lobe and posterior corpus callosum was the most common. Enhancement MRI showed patchy Gd-enhancement of partial lesions in three cases. In two patients, magnetic resonance spectroscopy showed that choline (Cho) peak increased and N-acetyl-aspartate (NAA) peak decreased. Serum VLCFA levels of C26, C24/C22 and C26/C22 were elevated in six patients who underwent serum VLCFA examination. Seven patients underwent adrenal cortical function testing, of which six experienced adrenal cortical dysfunction. Six patients were cognitively impaired, four of whom had decreased MMSE and MoCA scores, and two of whom were unable to cooperate with the assessment due to severe cognitive impairment. Eight different ABCD1 gene mutations were identified, among which c.1750delC (p.H584Tfs*52) and c.160_170delACGCAGGAGGC (p.T54Lfs*137) were novel mutations.Conclusion·The initial symptoms of ACALD vary, among which memory loss and cognitive dysfunction are the most common. White matter demyelination lesions in the parietal and corpus callosum pressure are the most common, and imaging abnormalities precede neurological symptoms. The clinical features of the disease are hair thinning and skin pigmentation, and the biochemical features are elevated serum VLCFA and adrenal insufficiency. Missense mutations are more common in the ABCD1 gene, and exons 1 and 6 are the hot mutant exons in Chinese.

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]

The dynamic stability of dense medium suspension is the premise to ensure the effective separation of mineral particles in the separation equipment. It is usually difficult to directly measure the dynamic stability of the suspension in the separation process of the dense medium cyclone. In this paper, a parameter defined as the density difference value between the underflow and overflow of cyclone is used to characterize the dynamic stability of the suspension in the separation process. Under the conditions of different operating parameters and structural parameters, the influencing factors of the dynamic stability of 1.30–1.60 g/cm3 dense medium suspension are systematically studied. The results show that the parameter value is in the range of 0.20–0.50 g/cm3, which is conducive to the separation of particles. When the suspension density increases, the characteristic value of density difference decreases, the influence of the suspension density, feed pressure, the diameter of underflow and overflow port diameter on the density difference characteristic are also researched. Eventually, the formula for calculating the density difference of the characteristic value of suspension is derived. [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]