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The degeneration of the neuromuscular junction (NMJ) and the decline in motor function are common features of aging, but the underlying mechanisms have remained largely unclear. This study reveals that Sirt6 is reduced in aged mouse muscles. Ablation of Sirt6 in skeletal muscle causes a reduction of Dystrophin levels, resulting in premature NMJ degeneration, compromised neuromuscular transmission, and a deterioration in motor performance. Mechanistic studies show that Sirt6 negatively regulates the stability of the Dystrophin repressor YY1 (Yin Yang 1). Specifically, Sirt6 mono‐ADP‐ribosylates YY1, causing its disassociation from the Dystrophin promoter and allowing YY1 to bind to the SMURF2 E3 ligase, leading to its degradation. Importantly, supplementation with nicotinamide mononucleotide (NMN) enhances the mono‐ADP‐ribosylation of YY1 and effectively delays NMJ degeneration and the decline in motor function in elderly mice. These findings provide valuable insights into the intricate mechanisms underlying NMJ degeneration during aging. Targeting Sirt6 could be a potential therapeutic approach to mitigate the detrimental effects on NMJ degeneration and improve motor function in the elderly population. [ABSTRACT FROM AUTHOR]

INTRODUCTION: This study aims to explore the current status of dementia‐specific diagnosis and treatment in China. METHODS: This national survey was conducted in mainland China from September 2022 to February 2023, with strong support from the Cognitive Disorders Group of the Chinese Society of Neurology, Chinese Medical Association. RESULTS: Among 2721 hospitals surveyed, 244 (8.97%) have dementia‐specific clinics (DSCs) and 166 (6.10%) have dementia‐specific inpatient departments (DSIDs). Almost all hospitals have brain structural imaging capabilities and basic hematological examinations, but dementia‐specific medical staff (DSMS) equipped for DSCs or DSIDs are rare. The proportion of patients with cognitive impairment receiving care through a DSCs or DSIDs is low, and most patients present with advanced (moderate to severe) disease. CONCLUSION: The survey shows that the proportion of DSCs and DSIDs is low, and the regional distribution varies significantly. Trained DSMS and specialized facilities for the diagnosis and treatment of dementia are inadequate. Highlights: This study was a multi‐center national research to comprehensively investigate the distribution and features of dementia‐specific clinics and inpatient departments in mainland China, given that the limited literature was available regarding the dementia‐specific centers.The study points to significant regional differences in the distribution of cognitive‐specific clinics and inpatient departments in mainland China. More centers in Eastern Regions compared to Western Regions, a greater presence in provincial capitals as opposed to other cities, and a predominance of tertiary hospitals over non‐tertiary ones. The aim is to provide data support for advancements in medical research within this field.Domestic dementia patients have inadequate access to specialized medical resources and expert assistance, which significantly contrasts with the growing number of dementia cases in China. [ABSTRACT FROM AUTHOR]

In neuroinflammation, distinguishing microglia from macrophages and identifying microglial-specific biomarkers in peripheral blood pose significant challenges. This study comprehensively profiled the extracellular vesicles (EVs) of microglia and macrophages, respectively, revealing co-expressed EVs with UCHL1 and CX3CR1 as EVs derived specifically from microglia in human blood. After extensive validation, using optimized nano flow cytometry, we evaluated plasma CX3CR1+/UCHL1+ EVs across clinical cohorts [multiple sclerosis (MS), HTLV-1 associated myelopathy (HAM), Alzheimer's disease (AD), and Parkinson's disease (PD)], along with established neurodegenerative markers (NMDAR2A and NFL). The findings discovered a notable rise in CX3CR1+/UCHL1+ EVs in MS, particularly heightened in HAM, in contrast to controls. Conversely, AD and PD exhibited unaltered or diminished levels of microglial EVs. An integrated model of CX3CR1+/UCHL1+, NMDAR2A+, and NFL+ EVs demonstrated promising diagnostic potential for distinguishing MS from controls and HAM. As to the disease duration, CX3CR1+/UCHL1+ EVs increased in the initial five years of MS, stabilizing thereafter, whereas NMDAR2A+ and NFL+ EVs remained stable initially but increased significantly in the subsequent five years, suggesting their correlation with disease duration. This study uncovers unique blood microglial EVs with potential as biomarkers for MS diagnosis, differentiation from HAM, and correlation with disease duration. [ABSTRACT FROM AUTHOR]

Eupatorium lindleyanum DC. (EL) is a traditional Chinese herb known for its phlegm-reducing, cough-relieving and asthma-calming properties. It is widely used for treating cough and bronchitis. However, preliminary experiments have revealed wide variations in the composition of its different medicinal parts (flowers, leaves and stems), and the composition and efficacy of its different medicinal parts remain largely underexplored at present. In this study, non-targeted rapid resolution liquid chromatography coupled with a quadruple time-of-flight mass spectrometry (RRLC-Q-TOF-MS)-based metabolomics approach was developed to investigate the differences in the chemical composition of different medicinal parts of EL. We identified or tentatively identified 9 alkaloids, 11 flavonoids, 14 sesquiterpene lactones, 3 diterpenoids and 24 phenolic acids. In addition, heatmap visualization, quantitative analysis by high-performance liquid chromatography (HPLC-PDA) and ultra-high-performance liquid chromatography–triple quadrupole tandem mass spectrometry (UPLC-MS/MS) showed particularly high levels of sesquiterpene lactones, flavonoids and phenolic acids in the flowers, such as eupalinolide A and B and chlorogenic acid, among others. The leaves also contained some flavonoid sesquiterpene lactones and phenolic acids, while the stems were almost absent. The findings of in vitro activity studies indicated that the flowers exhibited a notable inhibitory effect on the release of the inflammatory factors TNF-α and IL-6, surpassing the anti-inflammatory efficacy observed in the leaves. Conversely, the stems demonstrated negligible anti-inflammatory activity. The variations in anti-inflammatory activity among the flowers, leaves and stems of EL can primarily be attributed to the presence of flavonoids, phenolic acids and sesquiterpene lactones in both the flowers and leaves. Additionally, the flowers contain a higher concentration of these active components compared to the leaves. These compounds mediate their anti-inflammatory effects through distinct biochemical pathways. The results of this study are anticipated to provide a scientific basis for the rational and effective utilization of EL resources. [ABSTRACT FROM AUTHOR]

Alzheimer's disease has escalated into a critical public health concern, marked by its neurodegenerative nature that progressively diminishes cognitive abilities. Recognized as a continuously advancing and presently incurable condition, AD underscores the necessity for early-stage diagnosis and interventions aimed at delaying the decline in mental function. Despite the proven efficacy of cerebrospinal fluid and positron emission tomography in diagnosing AD, their broader utility is constrained by significant costs and the invasive nature of these procedures. Consequently, the innovation of blood biomarkers such as Amyloid-beta, phosphorylated-tau, total-tau et al, distinguished by their high sensitivity, minimal invasiveness, accessibility, and cost-efficiency, emerges as a promising avenue for AD diagnosis. The advent of ultra-sensitive detection methodologies, including single-molecule enzyme-linked immunosorbent assay and immunoprecipitation-mass spectrometry, has revolutionized the detection of AD plasma biomarkers, supplanting previous low-sensitivity techniques. This rapid advancement in detection technology facilitates the more accurate quantification of pathological brain proteins and AD-associated biomarkers in the bloodstream. This manuscript meticulously reviews the landscape of current research on immunological markers for AD, anchored in the National Institute on Aging—Alzheimer's Association AT(N) research framework. It highlights a selection of forefront ultra-sensitive detection technologies now integral to assessing AD blood immunological markers. Additionally, this review examines the crucial pre-analytical processing steps for AD blood samples that significantly impact research outcomes and addresses the practical challenges faced during clinical testing. These discussions are crucial for enhancing our comprehension and refining the diagnostic precision of AD using blood-based biomarkers. The review aims to shed light on potential avenues for innovation and improvement in the techniques employed for detecting and investigating AD, thereby contributing to the broader field of neurodegenerative disease research. [ABSTRACT FROM AUTHOR]

To address the problem of low accuracy of construction schedule prediction in location-based management systems (LBMS), this paper adopts Harmony Search Algorithm (HS) to optimize the weights and thresholds of BP neural networks. By integrating practical construction information, an LBMS framework based on HS-BP neural networks is constructed to accurately predict the construction schedule. Finally, the prediction accuracy of HS-BP neural network is verified by taking the construction schedule of roof slab formwork of Guangzhou Guanglianda South China Headquarters Base Project as an example. The flow line of the actual and predicted schedules of the beam slab are also drawn to illustrate the reliability of the LBMS framework based on HS-BP neural network. [ABSTRACT FROM AUTHOR]

[Objective] The pharmaceutical process's component transmission behavior is determined by its molecular state. Currently, infrared spectroscopy, nuclear magnetic resonance, differential thermal analysis, high-resolution scanning electron microscopy, and other techniques are used to analyze the molecular state of pharmacological components. Nevertheless, to apply the aforementioned technologies, the components must be isolated from the original solution. Using the detection principle, a qualitative analysis of the component status can be produced, but the precise ratio of ionic, molecular, and other states cannot be determined. In this work, a teaching experiment was designed for the quantitative calculation of the molecular state of rosmarinic acid using a nanofiltration mass transfer model. [Methods] Using the theory that "nanofiltration mass transfer coefficient can represent the difficulty of components passing through nanofiltration membrane pores, and is a manifestation of comprehensive separation of multiple states of existence," this study developed an experimental teaching program based on the nanofiltration mass transfer model for the quantitative analysis of drug ingredient molecular states. Given that rosmarinic acid has a pKa of 4.01, a 5% hydrochloric acid solution was used, and the mass concentration was adjusted to 0.210 mg/mL. The pH of the rosmarinic acid monomer component solution was 2.01, implying that 99% of the molecular state of rosmarinic acid was present. The rosmarinic acid solution was put in the liquid storage tank, and the system pressures of the nanofiltration apparatus were changed to 0.6, 0.8, 1.0, 1.2, and 1.4 MPa, respectively. The nanofiltration liquid and membrane flux (Jv) were then collected at an appropriate pressure. Using high-performance liquid chromatography, the rosmarinic acid solution and filtrate were identified, and the retention rate (R) was computed. The linear equation of ln[(1 - R)Jv/R] and the nanofiltration mass transfer coefficient of rosmarinic acid (k) were fitted using the correlation among k and R and Jv. Subsequently, the power function equations for k and rosmarinic acid concentration (C) were fitted, and the extracted liquid of Salvia miltiorrhiza was separated using nanofiltration, with the proportion of rosmarinic acid molecular states determined using the power function equations of the concentration and mass transfer coefficient of this monomeric component. Furthermore, the relationship between the transfer rate and the component molecular states during the alcohol precipitation, resin adsorption, clarity filtration, concentration, and drying processes was investigated. [Results] Rosmarinic acid had a molecular proportion of 33.62% in Salvia miltiorrhiza extract. Rosmarinic acid's solubility in ethanol solution fell as its molecular proportion dropped, and it was easily adsorbed by polysaccharide, protein, and colloid components during alcohol precipitation, resulting in a decrease in alcohol precipitation transfer rate. Rosmarinic acid was difficult to adsorb on the surface of the macroporous resin, and the transfer rate increased as the aqueous solution flowed out. Rosmarinic acid had a substantial interfacial adsorption impact on the surface of the microfiltration membrane, leading to component loss.The results showed that the existence of rosmarinic acid had a significant effect on the component transfer rate in the pharmaceutical process, which aided in the standardization of the manufacturing process. [Conclusions] This experiment combined important pharmaceutical issues with scientific research to feed teaching, develop students' scientific research literacy and practical ability, and realize the collaborative improvement of scientific research application and teaching expansion. [ABSTRACT FROM AUTHOR]