Association between weight-adjusted waist index and periodontitis: A population-based study.

OBJECTIVE: This study aims to examine the association between the Weight-adjusted Waist Circumference Index (WWI) and the prevalence of periodontitis, providing novel evidence on the link between central obesity and periodontal health. METHODS: A cross-sectional study was conducted with 10,289 participants enrolled from NHANES 2009 to 2014. WWI was calculated by dividing waist circumference by the square root of weight. We employed a multivariate logistic regression model and smoothed curve fitting method to evaluate the relationship between WWI and periodontitis. We also compared different subgroups and analyzed the interaction effects. RESULTS: A significant positive association between WWI and periodontitis was observed in 10,289 participants aged ≥30 (OR: 1.20, 95% CI: 1.12-1.28). Upon categorizing WWI into quartiles, the top quartile group exhibited a 27% increased prevalence of periodontitis compared to the bottom quartile (OR: 1.27, 95% CI: 1.10-1.46; P for trend = 0.001). Among individuals aged 30 to 60, the strength of this positive correlation is more pronounced than in those aged 60 and above. CONCLUSIONS: WWI demonstrates a positive correlation with periodontitis with a particularly pronounced impact on moderate periodontitis, suggesting its potential to improve periodontitis prevention in a broad population.

Effects of a UV absorber in silica-loaded resin on DLP silica fiber preform fabrication.

3D printing technologies have distinguished advantages in manufacturing arbitrary shapes and complex structures that have attracted us to use digital light processing (DLP) technology for specialty silica optical fiber preforms. One of the main tasks is to develop an appropriate recipe for DLP resin that is UV sensitive and loaded with silica nanoparticles. In this work, the effects of a UV absorber in highly silica-loaded resin on DLP printing are experimentally investigated. Spot tests and DLP printing are carried out on resins with varying dosages of a typical UV absorber, Sudan Orange G. Based on the experimental results, the UV absorber can significantly improve the resolution of DLP printed green bodies while requiring a larger exposure dose.

Urban flood modeling with a novel coupling method of surface and sewer hydrodynamic processes.

Drainage modeling that accurately captures urban storm inundation serves as the foundation for flood warning and drainage scheduling. In this paper, we proposed a novel coupling ideology that, by integrating 2D-1D and 1D-2D unidirectional processes, overcomes the drawback of the conventional unidirectional coupling approach that fails to properly represent the rainfall surface catchment dynamics, and provides more coherent hydrological implications compared to the bidirectional coupling concept. This paper first referred to a laboratory experimental case from the literature, applied and analyzed the coupling scheme proposed in this paper and the bidirectional coupling scheme that has been widely studied in recent years, compared the two coupling solutions in terms of the resulting accuracy and applicability, and discussed their respective strengths and weaknesses to validate the reliability of the proposed method. The verified proposed coupling scheme was then applied to the modeling of a real drainage system in a region of Nanjing, China, and the results proved that the coupling mechanism proposed in this study is of practical application value.

Polydatin, a potential NOX5 agonist, synergistically enhances antitumor activity of cisplatin by stimulating oxidative stress in non­small cell lung cancer.

Non­small cell lung cancer (NSCLC) is one of the major causes of cancer­related death worldwide. Cisplatin is a front­line chemotherapeutic agent in NSCLC. Nevertheless, subsequent harsh side effects and drug resistance limit its further clinical application. Polydatin (PD) induces apoptosis in various cancer cells by generating reactive oxygen species (ROS). However, underlying molecular mechanisms of PD and its effects on cisplatin­mediated antitumor activity in NSCLC remains unknown. MTT, colony formation, wound healing analyses and flow cytometry was employed to investigate the cell phenotypic changes and ROS generation. Relative gene and protein expressions were evaluated by reverse transcription­quantitative PCR and western blot analyses. The antitumor effects of PD, cisplatin and their combination were evaluated by mouse xenograft model. In the present study, it was found that PD in combination with cisplatin synergistically enhances the antitumor activity in NSCLC by stimulating ROS­mediated endoplasmic reticulum stress, and the C­Jun­amino­terminal kinase and p38 mitogen­activated protein kinase signaling pathways. PD treatment elevated ROS generation by promoting expression of NADPH oxidase 5 (NOX5), and NOX5 knockdown attenuated ROS­mediated cytotoxicity of PD in NSCLC cells. Mice xenograft model further confirmed the synergistic antitumor efficacy of combined therapy with PD and cisplatin. The present study exhibited a superior therapeutic strategy for some patients with NSCLC by combining PD and cisplatin.

Enhancing the Thermal Stability and Enzyme Activity of Ketopantoate Hydroxymethyltransferase through Interface Modification Engineering.

Ketopantoate hydroxymethyltransferase (KPHMT) plays a pivotal role in d-pantothenic acid biosynthesis. Most KPHMTs are homodecamers with low thermal stability, posing challenges for protein engineering and limiting output enhancement. Previously, a high-enzyme activity KPHMT mutant (K25A/E189S) from Corynebacterium glutamicum was screened as mother strain (M0). Building upon this strain, our study focused on interface engineering modifications, employing a multifaceted approach including integrating folding-free energy calculation, B-factor analysis, and conserved site analysis. Preliminary screening led to the selection of five mutants in the interface─E106S, E98T, E98N, S247I, and S247D─showing improved thermal stability, culminating in the double-site mutant M8 (M0-E98N/S247D). M8 exhibited a T1/2 value of 288.79 min at 50 °C, showing a 3.29-fold increase compared to M0. Meanwhile, the Tm value of M8 was elevated from 53.2 to 59.6 °C. Investigations of structural and molecular dynamics simulations revealed alterations in surface electrostatic charge distribution and the formation of increased hydrogen bonds between subunits, contributing to enhanced thermal stability. This investigation corroborates the efficacy of interface engineering modifications in bolstering KPHMT stability while showing its potential for positively impacting industrial d-pantothenic acid synthesis.

Melanin in Auricularia auricula: biosynthesis, production, physicochemical characterization, biological functions, and applications.

Auricularia auricular (A. auricula), a nutritious fungus and traditional medicinal resource, is known for melanin. This review aims to summarize the research progress on melanin in A. auricula, specifically focusing on biosynthesis, fermentation production, extraction processes, physicochemical characterization, biological functions, and applications. The biosynthesis of melanin in A. auricula primarily involves the oxidative polymerization reaction of phenolic compounds. To enhance melanin production, strategies such as deep fermentation culture, selection of optimal fermentation materials, and optimization of the culture medium have been employed. Various extraction processes have been compared to determine their impact on the physicochemical properties and stability of melanin. Moreover, the antioxidant and antibiofilm activities of A. auricula melanin, as well as its potential beneficial effects on the human body through in vivo experiments, have been investigated. These findings provide valuable insights into the application of A. auricula melanin and serve as a reference for future research in this field.

Desloratadine ameliorates paclitaxel-induced peripheral neuropathy and hypersensitivity reactions in mice.

Paclitaxel (PTX) serves as a primary chemotherapy agent against diverse solid tumors including breast cancer, lung cancer, head and neck cancer and ovarian cancer, having severe adverse effects including PTX-induced peripheral neuropathy (PIPN) and hypersensitivity reactions (HSR). A recommended anti-allergic agent diphenhydramine (DIP) has been used to alleviate PTX-induced HSR. Desloratadine (DLT) is a third generation of histamine H1 receptor antagonist, but also acted as a selective antagonist of 5HTR2A. In this study we investigated whether DLT ameliorated PIPN-like symptoms in mice and the underlying mechanisms. PIPN was induced in male mice by injection of PTX (4 mg/kg, i.p.) every other day for 4 times. The mice exhibited 50% reduction in mechanical threshold, paw thermal response latency and paw cold response latency compared with control mice. PIPN mice were treated with DLT (10, 20 mg/kg, i.p.) 30 min before each PTX administration in the phase of establishing PIPN mice model and then administered daily for 4 weeks after the model was established. We showed that DLT administration dose-dependently elevated the mechanical, thermal and cold pain thresholds in PIPN mice, whereas administration of DIP (10 mg/kg, i.p.) had no ameliorative effects on PIPN-like symptoms. We found that the expression of 5HTR2A was selectively elevated in the activated spinal astrocytes of PIPN mice. Spinal cord-specific 5HTR2A knockdown by intrathecal injection of AAV9-5Htr2a-shRNA significantly alleviated the mechanical hyperalgesia, thermal and cold hypersensitivity in PIPN mice, while administration of DLT (20 mg/kg) did not further ameliorate PIPN-like symptoms. We demonstrated that DLT administration alleviated dorsal root ganglion neuronal damage and suppressed sciatic nerve destruction, spinal neuron apoptosis and neuroinflammation in the spinal cord of PIPN mice. Furthermore, we revealed that DLT administration suppressed astrocytic neuroinflammation via the 5HTR2A/c-Fos/NLRP3 pathway and blocked astrocyte-neuron crosstalk by targeting 5HTR2A. We conclude that spinal 5HTR2A inhibition holds promise as a therapeutic approach for PIPN and we emphasize the potential of DLT as a dual-functional agent in ameliorating PTX-induced both PIPN and HSR in chemotherapy. In summary, we determined that spinal 5HTR2A was selectively activated in PIPN mice and DLT could ameliorate the PTX-induced both PIPN- and HSR-like pathologies in mice. DLT alleviated the damages of DRG neurons and sciatic nerves, while restrained spinal neuronal apoptosis and CGRP release in PIPN mice. The underlying mechanisms were intensively investigated by assay against the PIPN mice with 5HTR2A-specific knockdown in the spinal cord by injection of adeno-associated virus 9 (AAV9)-5Htr2a-shRNA. DLT inhibited astrocytic NLRP3 inflammasome activation-mediated spinal neuronal damage through 5HTR2A/c-FOS pathway. Our findings have supported that spinal 5HTR2A inhibition shows promise as a therapeutic strategy for PIPN and highlighted the potential advantage of DLT as a dual-functional agent in preventing against PTX-induced both PIPN and HSR effects in anticancer chemotherapy.

The role of oxidative stress biomarkers in the development of peri-implant disease: A systematic review and meta-analysis.

OBJECTIVES: To analyze the role of oxidative stress (OS) biomarkers in peri­implant diseases using a systematic review and meta-analysis approach. DATE: The review incorporated cross-sectional studies, randomized controlled trials, and case-control trials to evaluate the differences in OS biomarkers of peri­implant disease. SOURCES: A comprehensive literature search was conducted in electronic databases such as PubMed, Scopus, Embase, Web of Science, and CNKI, and no restrictions were applied during the search process. STUDY SELECTION: A total of 452 studies were identified, of which 18 were eligible for inclusion. Risk of bias and sensitivity analysis were assessed using Egger's test and funnel plots. RESULTS: We found that the levels of glutathione peroxidase (GSH-Px) in the peri­implant sulcus fluid (PISF) of patients with peri­implant diseases were significantly reduced (SMD = -1.40; 95 % CI = 1.70, -1.11; p < 0.001), while the levels of total myeloperoxidase (MPO) and malondialdehyde (MDA) were significantly increased (SMD = 0.46; 95 % CI = 0.12, 0.80; p = 0.008; SMD = 0.28; 95 % CI = 0.01, 0.56; p = 0.043). However, there were no significant differences of MPO concentration (SMD = 0.38; 95 % CI = -0.39, 1.15; p = 0.331) and superoxide dismutase (SOD)(SMD = -0.43; 95 % CI = -1.94, 1.07; p = 0.572) in PISF between peri­implant disease group and control group. Similarly, salivary MPO did not show significant differences (SMD = 1.62; 95 % CI = -1.01, 4.24; p = 0.227). CONCLUSIONS: Our results supported that the level of local OS biomarkers was closely related to peri­implant diseases. GSH-Px, total MPO and MDA may be PISF biomarkers with good capability to monitor the development of peri­implant disease. CLINICAL SIGNIFICANCE: This study found significant differences in the levels of local OS biomarkers (GSH-Px, total MPO, and MDA) between patients with peri­implant diseases and healthy subjects, which may be ideal candidate biomarkers for predicting and diagnosing peri­implant diseases.

cla-miR164-NO APICAL MERISTEM (ClNAM) regulates the inflorescence architecture development of Chrysanthemum lavandulifolium.

Chrysanthemum × morifolium has great ornamental and economic value on account of its exquisite capitulum. However, previous studies have mainly focused on the corolla morphology of the capitulum. Such an approach cannot explain the variable inflorescence architecture of the chrysanthemum. Previous research from our group has shown that NO APICAL MERISTEM (ClNAM) is likely to function as a hub gene in capitulum architecture in the early development stage. In the present study, ClNAM was used to investigate the function of these boundary genes in the capitulum architecture of Chrysanthemum lavandulifolium, a closely related species of C. × morifolium in the genus. Modification of ClNAM in C. lavandulifolium resulted in an advanced initiation of the floral primordium at the capitulum. As a result, the receptacle morphology was altered and the number of florets decreased. The ray floret corolla was shortened, but the disc floret was elongated. The number of capitula increased significantly, arranged in more densely compounded corymbose synflorescences. The yeast and luciferase reporter system revealed that ClAP1, ClRCD2, and ClLBD18 target and activate ClNAM. Subsequently, ClNAM targets and activates ClCUC2a/c, which regulates the initiation of floral and inflorescence in C. lavandulifolium. ClNAM was also targeted and cleaved by cla-miR164 in this process. In conclusion, this study established a boundary gene regulatory network with cla-miR164-ClNAM as the hub. This network not only influences the architecture of capitulum, but also affects compound corymbose synflorescences of the C. lavandulifolium. These results provide new insights into the mechanisms regulating inflorescence architecture in chrysanthemum.

New method for calculating the windward area of irregular fragments.

Average windward area is an important index for calculating the trajectory, velocity attenuation and terminal effect of explosive fragments. In order to solve the problems that existing theoretical method cannot calculate windward area of irregular fragment and experiment method is not convenient for automatic calculation and has low accuracy, a Monte Carlo subdivision projection simulation algorithm is proposed. The average windward area of arbitrary shaped fragments can be obtained with coordinate translation, random rotation, plane projection, convex-hull triangulation, concave boundary searching and sorting with maximum edge length constraint, subdivision area calculation, and averaging by thousands of cycles. Results show that projection area obtained by the subdivision projection algorithm is basically the same as that obtained by software method of computer aided design. Moreover, the maximum calculation error of the algorithm is less than 7%, and its accuracy is much higher than that of the equivalent ellipsoid method. The average windward area calculated by the Monte Carlo subdivision projection simulation algorithm is consistent with theoretical formula for prefabricated fragments, and the error is less than 3%. The convergence and accuracy of the Monte Carlo subdivision projection algorithm are better than those of the icosahedral uniform orientation method.

Pharmacokinetics, pharmacodynamics, and safety of frunexian in healthy Chinese volunteer adults: A randomized dose-escalation phase I study.

The purpose of this study was to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of frunexian (formerly known as EP-7041 and HSK36273) injection, a small molecule inhibitor of activated coagulation factor XI (FXIa), in healthy Chinese adult volunteers. This study was a randomized, placebo- and positive-controlled, sequential, ascending-dose (0.3/0.6/1.0/1.5/2.25 mg/kg/h) study of 5-day continuous intravenous infusions of frunexian. Frunexian administration exhibited an acceptable safety profile with no bleeding events. Steady state was rapidly reached with a median time ranging from 1.02 to 1.50 h. The mean half-life ranged from 1.15 to 1.43 h. Frunexian plasma concentration at a steady state and area under the concentration-time curve exhibited dose-proportional increases. The dose-escalation study of frunexian demonstrated its progressively enhanced capacities to prolong activated partial thromboplastin time (aPTT) and inhibit FXIa activity. The correlations between PK and PD biomarkers (aPTT/baseline and FXI clotting activity/baseline) were described by the two Emax models, with the EC50 values of 8940 and 1300 ng/mL, respectively. Frunexian exhibits good safety and PK/PD properties, suggesting it is a promising candidate for anticoagulant drug.

Exploring the Micropore Functional Mechanism of N2O Adsorption by the Eucalyptus Bark-based Porous Carbon.

Nitrous oxide (N2O), recognized as a significant greenhouse gas, has received insufficient research attention in the past. In view of their low energy consumption and cost-effectiveness, the application of porous materials in adsorption is increasingly regarded as a potent strategy to reduce N2O pollution. In this study, a series of microporous porous carbons with a preeminent specific surface area (244.54-2018.08 m2 g-1), which are derived from the fast-growing eucalyptus bark, were synthesized by KOH activation at high temperatures. The obtained materials demonstrated a relatively fine N2O capture capability (0.19-0.68 mmol g-1) at normal temperature and pressure. More importantly, the optimal pore size affecting N2O adsorption (0.8 and 1.0 nm) has been detected, which is a meaningful view that has never been put forward in previous studies. The rationality of the N2O adsorption mechanism was also validated by combining the experimental analysis and Grand Canonical Monte Carlo (GCMC) simulation. The calculated results showed that 0.8 and 1.0 nm of the porous carbon were the preferred pore sizes for N2O adsorption, and the interaction force between N2O and the pore wall decreased with the increase of distance. This study provides a significant theoretical basis for the preparation of biomass porous carbon with excellent N2O adsorption performance and practical adsorption application.

Identifying topology of distribution substation in power Internet of Things using dynamic voltage load fluctuation flow analysis.

At present, the reconfiguration, maintenance, and review of power lines play a pivotal role in maintaining the stability of electrical grid operations and ensuring the accuracy of electrical energy measurements. These essential tasks not only guarantee the uninterrupted functioning of the power system, thereby improving the reliability of the electricity supply but also facilitate precise electricity consumption measurement. In view of these considerations, this article endeavors to address the challenges posed by power line restructuring, maintenance, and inspections on the stability of power grid operations and the accuracy of energy metering. To accomplish this goal, this article introduces an enhanced methodology based on the hidden Markov model (HMM) for identifying the topology of distribution substations. This approach involves a thorough analysis of the characteristic topology structures found in low-voltage distribution network (LVDN) substations. A topology identification model is also developed for LVDN substations by leveraging time series data of electricity consumption measurements and adhering to the principles of energy conservation. The HMM is employed to streamline the dimensionality of the electricity consumption data matrix, thereby transforming the topology identification challenge of LVDN substations into a solvable convex optimization problem. Experimental results substantiate the effectiveness of the proposed model, with convergence to minimal error achieved after a mere 50 iterations for long time series data. Notably, the method attains an impressive discriminative accuracy of 0.9 while incurring only a modest increase in computational time, requiring a mere 35.1 milliseconds. By comparison, the full-day data analysis method exhibits the shortest computational time at 16.1 milliseconds but falls short of achieving the desired accuracy level of 0.9. Meanwhile, the sliding time window analysis method achieves the highest accuracy of 0.95 but at the cost of a 50-fold increase in computational time compared to the proposed method. Furthermore, the algorithm reported here excels in terms of energy efficiency (0.89) and load balancing (0.85). In summary, the proposed methodology outperforms alternative approaches across a spectrum of performance metrics. This article delivers valuable insights to the industry by fortifying the stability of power grid operations and elevating the precision of energy metering. The proposed approach serves as an effective solution to the challenges entailed by power line restructuring, maintenance, and inspections.

Decoupled oxidation process enabled by atomically dispersed copper electrodes for in-situ chemical water treatment.

In-situ wastewater treatment has gained popularity due to cost and energy savings tailored to water sources and user needs. However, this treatment, particularly through advanced oxidation processes (AOPs), poses ecological risks due to the need for strong oxidizing agents. Here, we present a decoupled oxidation process (DOP) using single-atom copper-modified graphite felt electrodes. This process creates a positive potential difference (ΔE ~ 0.5 V) between spatially isolated oxidants and organics and drives electron transfer-based redox reactions. The approach avoids the drawbacks of conventional AOPs, while being capable of treating various recalcitrant electron-rich organics. A floating water treatment device designed based on the DOP approach can degrade organic molecules in large bodies of water with oxidants stored separately in the device. We demonstrate that over 200 L of contaminated water can be treated with a floating device containing only 40 mL of oxidant (10 mM peroxysulphate). The modular device can be used in tandem structures on demand, maximizing water remediation per unit area. Our result provides a promising, eco-friendly method for in-situ water treatment that is unattainable with existing techniques.

XIAP-mediated degradation of IFT88 disrupts HSC cilia to stimulate HSC activation and liver fibrosis.

Activation of hepatic stellate cells (HSCs) plays a critical role in liver fibrosis. However, the molecular basis for HSC activation remains poorly understood. Herein, we demonstrate that primary cilia are present on quiescent HSCs but exhibit a significant loss upon HSC activation which correlates with decreased levels of the ciliary protein intraflagellar transport 88 (IFT88). Ift88-knockout mice are more susceptible to chronic carbon tetrachloride-induced liver fibrosis. Mechanistic studies show that the X-linked inhibitor of apoptosis (XIAP) functions as an E3 ubiquitin ligase for IFT88. Transforming growth factor-ß (TGF-ß), a profibrotic factor, enhances XIAP-mediated ubiquitination of IFT88, promoting its proteasomal degradation. Blocking XIAP-mediated IFT88 degradation ablates TGF-ß-induced HSC activation and liver fibrosis. These findings reveal a previously unrecognized role for ciliary homeostasis in regulating HSC activation and identify the XIAP-IFT88 axis as a potential therapeutic target for liver fibrosis.

Causal association between telomere length and colorectal polyps: A bidirectional two-sample Mendelian randomization study.

We performed a bidirectional 2-sample Mendelian randomization (MR) design to explore the causal relation between telomere length (TL) and colorectal polyps. Genome-wide association study summary data of TL and colorectal polyps were extracted from the IEU open genome-wide association study database. Single nucleotide polymorphisms were served as instrumental variables at the significance threshold of P < 5 × 10-8. The inverse variance weighted method, MR-Egger method, and weight median method were performed for causal estimation in MR. Cochran Q test, MR-Egger intercept test, and leave-one-out analyses were performed to evaluate the pleiotropy of the MR results. One hundred and twenty-four single nucleotide polymorphisms were selected as instrumental variables. We found significant casual association between TL and colorectal polyps. Long TL increased the risk of colorectal polyps using the inverse variance weighted method [ukb-a-521: odds ratio (OR): 1.004, 95% confidence interval (CI): 1.001-1.007, P = .004; ukb-d-D12: OR: 1.008, CI: 1.004-1.012, P < .001; finn-b-CD2_BENIGN_COLORECANI_EXALLC2: OR: 1.170, CI: 1.027-1.332, P = .018]. Sensitivity analyses validated that the causality between TL and colorectal polyps was robust. The study provided a causal association between TL and colorectal polyps which indicated that TL might be served as a potential biomarker of colorectal polyps for screening and prevention. Nonetheless, the conclusions need further validation.

Improvements in the Appearance and Nutritional Quality of Tomato Fruits Resulting from Foliar Spraying with Silicon.

Research on silicon (Si), an element considered beneficial for plant growth, has focused on abiotic and biotic stress mitigation. However, the effect of Si on tomato fruit quality under normal growth conditions remains unclear. This study investigated the effects of applying different levels of Si (0 mmol·L-1 [CK], 0.6 mmol·L-1 [T1], 1.2 mmol·L-1 [T2], and 1.8 mmol·L-1 [T3]) in foliar sprays on tomato fruit quality cultivated in substrates, and the most beneficial Si level was found. Compared to CK, exogenous Si treatments had a positive influence on the appearance and nutritional quality of tomato fruits at the mature green, breaker, and red ripening stages. Of these, T2 treatment significantly increased peel firmness and single-fruit weight in tomato fruits. The contents of soluble sugars, soluble solids, soluble proteins, and vitamin C were significantly higher, and the nitrate content was significantly lower in the T2 treatment than in the CK treatment. Cluster analysis showed that T2 produced results that were significantly different from those of the CK, T1, and T3 treatments. During the red ripening stage, the a* values of fruits in the T2 treatment tomato were significantly higher than those in the other three treatments. Moreover, the lycopene and lutein contents of the T2 treatment increased by 12.90% and 17.14%, respectively, compared to CK. T2 treatment significantly upregulated the relative gene expression levels of the phytoene desaturase gene (PDS), the lycopene ε-cyclase gene (LCY-E), and the zeaxanthin cyclooxygenase gene (ZEP) in the carotenoid key genes. The total amino acid content in tomato fruits in the T2 treatment was also significantly higher than that of CK. In summary, foliar spraying of 1.2 mmol·L-1 exogenous Si was effective in improving the appearance and nutritional quality of tomato fruits under normal growth conditions. This study provides new approaches to further elucidate the application of exogenous silicon to improve tomato fruit quality under normal conditions.

Desloratadine alleviates ALS-like pathology in hSOD1G93A mice via targeting 5HTR2A on activated spinal astrocytes.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with progressive loss of motor neurons in the spinal cord, cerebral cortex and brain stem. ALS is characterized by gradual muscle atrophy and dyskinesia. The limited knowledge on the pathology of ALS has impeded the development of therapeutics for the disease. Previous studies have shown that autophagy and astrocyte-mediated neuroinflammation are involved in the pathogenesis of ALS, while 5HTR2A participates in the early stage of astrocyte activation, and 5HTR2A antagonism may suppress astrocyte activation. In this study, we evaluated the therapeutic effects of desloratadine (DLT), a selective 5HTR2A antagonist, in human SOD1G93A (hSOD1G93A) ALS model mice, and elucidated the underlying mechanisms. HSOD1G93A mice were administered DLT (20 mg·kg-1·d-1, i.g.) from the age of 8 weeks for 10 weeks or until death. ALS onset time and lifespan were determined using rotarod and righting reflex tests, respectively. We found that astrocyte activation accompanying with serotonin receptor 2 A (5HTR2A) upregulation in the spinal cord was tightly associated with ALS-like pathology, which was effectively attenuated by DLT administration. We showed that DLT administration significantly delayed ALS symptom onset time, prolonged lifespan and ameliorated movement disorders, gastrocnemius injury and spinal motor neuronal loss in hSOD1G93A mice. Spinal cord-specific knockdown of 5HTR2A by intrathecal injection of adeno-associated virus9 (AAV9)-si-5Htr2a also ameliorated ALS pathology in hSOD1G93A mice, and occluded the therapeutic effects of DLT administration. Furthermore, we demonstrated that DLT administration promoted autophagy to reduce mutant hSOD1 levels through 5HTR2A/cAMP/AMPK pathway, suppressed oxidative stress through 5HTR2A/cAMP/AMPK/Nrf2-HO-1/NQO-1 pathway, and inhibited astrocyte neuroinflammation through 5HTR2A/cAMP/AMPK/NF-κB/NLRP3 pathway in the spinal cord of hSOD1G93A mice. In summary, 5HTR2A antagonism shows promise as a therapeutic strategy for ALS, highlighting the potential of DLT in the treatment of the disease. DLT as a 5HTR2A antagonist effectively promoted autophagy to reduce mutant hSOD1 level through 5HTR2A/cAMP/AMPK pathway, suppressed oxidative stress through 5HTR2A/cAMP/AMPK/Nrf2-HO-1/NQO-1 pathway, and inhibited astrocytic neuroinflammation through 5HTR2A/cAMP/AMPK/NF-κB/NLRP3 pathway in the spinal cord of hSOD1G93A mice.

Validation of the DBP-1333b upper-arm blood pressure monitor according to the AAMI/ESH/ISO universal standard (ISO 81060-2:2018+Amd.1:2020).

To evaluate the accuracy of the DBP-1333b upper-arm blood pressure (BP) measuring device in the adult population according to the AAMI/ESH/ISO universal standard (ISO 81060-2:2018+Amd.1:2020). Subjects were recruited in the adult population. The test device was an arm-type electronic sphygmomanometer (DBP-1333b) and the reference device was a desktop sphygmomanometer (XJ11D). Using the BP data measured by the desktop sphygmomanometer as reference BP, the accuracy of the non-invasive BP module of the test device was evaluated to determine whether it met the requirements. Data from 90 individuals were analysed. According to Criterion 1, the mean difference of SBP between the test and reference device was 0.19 mmHg and the SD was 7.45 mmHg. The mean difference of DBP was -0.59 mmHg and the SD was 6.47 mmHg. The mean difference of both SBP and DBP was less than 5 mmHg, and the SD was less than 8 mmHg, which met the requirements. According to Criterion 2, SD of SBP was 5.79 mmHg, which was less than 6.95 mmHg and met the requirements. The SD of DBP was 5.58 mmHg, which was less than 6.93 mmHg and met the requirements. It was concluded that the DBP-1333b complies with the AAMI/ESH/ISO universal standard (ISO 81060-2:2018+Amd.1:2020) and can be recommended for use by the adults.