Explore the vast range of titles available.

α-Synucleinopathies are characterized by autonomic dysfunction and motor impairments. In the pure autonomic failure (PAF), α-synuclein (α-Syn) pathology is confined within the autonomic nervous system with no motor features, but mouse models recapitulating PAF without motor dysfunction are lacking. Here, we show that in TgM83 +/− mice, inoculation of α-Syn preformed fibrils (PFFs) into the stellate and celiac ganglia induces spreading of α-Syn pathology only through the autonomic pathway to both the central nervous system (CNS) and the autonomic innervation of peripheral organs bidirectionally. In parallel, the mice develop autonomic dysfunction, featured by orthostatic hypotension, constipation, hypohidrosis and hyposmia, without motor dysfunction. Thus, we have generated a mouse model of pure autonomic dysfunction caused by α-Syn pathology. This model may help define the mechanistic link between transmission of pathological α-Syn and the cardinal features of autonomic dysfunction in α-synucleinopathy. Autonomic dysfunction is a feature of some α-synucleinopathies, but there are no models of pure autonomic dysfunction associated with α-synuclein. Here the authors describe a mouse model of pure autonomic dysfunction without motor dysfunciton by injection of pre-formed fibrils of α-synuclein to the stellate and celiac ganglia.

Background As the global aging issue grows, dementia, particularly Alzheimer’s disease (AD), has become a major public health challenge for everyone. This study utilizes the Global Burden of Disease (GBD) database to analyze trends in the epidemiology of AD and other dementias from 1990 to 2021 and to predict future burdens to 2040. Methods We examined global, regional, and national data on AD and other dementias, focusing on incidence, prevalence, and Disability-Adjusted Life Years (DALYs). Joinpoint regression analysis was employed to identify significant changes in trends over time. The effects of age, period, and birth cohort on the risk of AD and other dementias were analyzed. Additionally, the impact of aging, population growth, and epidemiological changes on DALYs was assessed across different Socio-demographic Index (SDI) quintiles. Results The global burden of AD and other dementias has significantly increased, with the highest incidence, prevalence, and DALYs observed in East Asia. A notable increase in prevalence was observed in females over 65 years compared to males. Joinpoint regression analysis revealed substantial changes in trends in 1995, 2005, 2011, and 2019, with a noticeable acceleration post-2011, especially after 2019. Age was a significant risk factor, with a sharp increase in risk after 60 years of age. Epidemiological changes had a minor impact globally but varied by region and gender. Bayesian age-period-cohort modeling predicts sustained growth through 2040, with age-standardized incidence and prevalence rates projected to reach 144.85 and 821.80 per 100,000 respectively, driven predominantly by aging populations in high SDI regions and demographic expansion in low SDI regions. Conclusions The global burden of AD and other dementias is escalating, with a pronounced increase expected by 2040. This study highlights the need for targeted interventions, particularly in regions with higher burdens and among older populations. The findings underscore the importance of considering SDI, age, and gender when planning public health strategies to address the growing challenge of AD and other dementias.

This study investigated the mechanism by which fucoxanthin acts as a novel ferroptosis inducer to inhibit tongue cancer. The MTT assay was used to detect the inhibitory effects of fucoxanthin on SCC−25 human tongue squamous carcinoma cells. The levels of reactive oxygen species (ROS), mitochondrial membrane potential (MMP), glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), and total iron were measured. Reverse transcription–quantitative polymerase chain reaction (RT−qPCR) and Western blotting were used to assess glutathione peroxidase 4 (GPX4), nuclear factor erythroid 2−related factor 2 (Nrf2), Keap1, solute carrier family 7 member 11 (SLC7A11), transferrin receptor protein 1 (TFR1), p53, and heme oxygenase 1 (HO−1) expression. Molecular docking was performed to validate interactions. Compared with the control group, the activity of fucoxanthin−treated SCC−25 cells significantly decreased in a dose− and time−dependent manner. The levels of MMP, GSH, and SOD significantly decreased in fucoxanthin−treated SCC−25 cells; the levels of ROS, MDA, and total iron significantly increased. mRNA and protein expression levels of Keap1, GPX4, Nrf2, and HO−1 in fucoxanthin−treated cells were significantly decreased, whereas levels of TFR1 and p53 were significantly increased, in a concentration−dependent manner. Molecular docking analysis revealed that binding free energies of fucoxanthin with p53, SLC7A11, GPX4, Nrf2, Keap1, HO−1, and TFR1 were below −5 kcal/mol, primarily based on active site hydrogen bonding. Our findings suggest that fucoxanthin can induce ferroptosis in SCC−25 cells, highlighting its potential as a treatment for tongue cancer.

Human pharyngeal squamous cell carcinoma (HPSCC) is the most common malignancy in the head and neck region, characterized by high mortality and a propensity for metastasis. Fucoxanthin, a carotenoid isolated from brown algae, exhibits pharmacological properties associated with the suppression of tumor proliferation and metastasis. Nevertheless, its potential to inhibit HPSCC proliferation and metastasis has not been fully elucidated. This study represents the first exploration of the inhibitory effects of fucoxanthin on two human pharyngeal squamous carcinoma cell lines (FaDu and Detroit 562), as well as the mechanisms underlying those effects. The results showed dose-dependent decreases in the proliferation, migration, and invasion of HPSCC cells after fucoxanthin treatment. Further studies indicated that fucoxanthin caused a significant reduction in the expression levels of proteins in the phosphoinositide 3−kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) pathway, as well as the downstream proteins matrix metalloproteinase (MMP)−2 and MMP−9. Specific activators of PI3K/AKT reversed the effects of fucoxanthin on these proteins, as well as on cell proliferation and metastasis, in FaDu and Detroit 562 cells. Molecular docking assays confirmed that fucoxanthin strongly interacted with PI3K, AKT, mTOR, MMP−2, and MMP−9. Overall, fucoxanthin, a functional food component, is a potential therapeutic agent for HPSCC.

Cilioretinal artery occlusion is a serious condition that results in a sudden and severe decline in vision. There are various treatment methods for retinal artery occlusion, but their effect remains unclear. Cilioretinal artery occlusion post-intravitreal drug injection is rare, with no relevant reports published to date. A man in his early 50s was admitted to our department due to a nail injury to the right eye. The patient underwent exploratory and suture surgery for eyeball penetrating injury, intraocular foreign body removal, and intravitreal vancomycin injection. The patient’s preoperative visual acuity in the right eye was 0.1, which decreased to FC/5 cm one day after surgery. Wide-angle fundus photography revealed cilioretinal artery occlusion. We highly suspected that the sudden increase in intraocular pressure after intravitreal injection of vancomycin was the cause of cilioretinal artery occlusion in this case. Mouse nerve growth factor (30 μg) and anisodine hydrobromide tablets (3 mg) were used for neurotrophic and microcirculation-improving treatments. Follow-up fundus fluorescein angiography at 31 seconds on postoperative day 18 showed filling of the cilioretinal artery. At 14 months post-surgery, the patient’s right eye visual acuity recovered to 0.1. In conclusion, cilioretinal artery occlusion post-intravitreal vancomycin injection is an extremely rare but severe complication that significantly affects vision. Early diagnosis and timely treatment are vital in such cases.

In the analysis of power market economic evaluation indicators, it is more common to use technical data mining for data calculation based on technology maturity analysis. This paper is based on a distributed computing platform for data mining, and parallelizes the traditional FP-Growth algorithm, so that the FP-Growth algorithm can be applied to the mining of big data association rules. Experimental results show that the algorithm can greatly improve the efficiency of mining association rules for massive data. The model is trained and tested on a distributed cluster built into the laboratory using customer electricity data, and then the predictions are validated to determine whether the difference between the predicted values and historical data for the same period exceeded the set threshold.

Background/Aims: Pancreatic neuroendocrine tumors (pNETs) are rare neoplasms which arise from pancreatic islet cells. Recently, lncRNA MEG3 has been reported as a tumor suppressor in variety cancers. This study aimed to reveal the functional effects of MEG3 on pNETs which has not been uncovered previously. Methods: The expression of MEG3, miR-183, and BRI3 in BON1 cells were altered by transfection with their specific vectors/shRNA, or mimic/inhibitor. Thereafter, cell viability, apoptosis, the protein expressions of cell cycle related factors, and apoptosis associated factors, as well as cell migration and invasion were respectively assessed by typan blue staining, flow cytometry, western blotting, and transwell assay. Results: MEG3 was low expressed in BON1 and QGP-1 cells, when compared to three normal cell lines (HEK293, CCL-153, and EC-304). MEG3 overexpression decreased BON1 cells viability, invasion, migration, but significantly induced apoptosis. miR-183 was a direct target of MEG3, and miR-183 up-regulation abolished the anti-growth and anti-metastasis effects of MEG3 overexpression on BON1 cells. Moreover, BRI3 was a target of miR-183, and BRI3 exhibited a tumor-promoting role possibly via activation of p38/ERK/AKT and Wnt/β-Catenin signaling in BON1 cells. Conclusion: This study demonstrated a tumor suppressive effect of MEG3 in BON1 cells that suppresses tumor cells growth and metastasis. A novel regulatory mechanism has been revealed that modulation of MEG3/miR-183/BRI3 axis may be pivotal in pNET.

BackgroundCurrently, the role of immunotherapy in neoadjuvant setting for patients with locally advanced esophageal squamous cell carcinoma (ESCC) is gradually attracting attention. Few studies compared the efficacy of neoadjuvant immunochemotherapy (NICT) and neoadjuvant chemoradiotherapy (NCRT). Our study aimed to compare treatment response and postoperative complications after NICT followed by surgery with that after conventional NCRT in patients with locally advanced ESCC.MethodsOf 468 patients with locally advanced ESCC, 154 received conventional NCRT, whereas 314 received NICT. Treatment response, postoperative complications and mortality between two groups were compared. Pathological response of primary tumor was evaluated using the Mandard tumor regression grade (TRG) scoring system. Pathological complete response (pCR) of metastatic lymph nodes (LNs) was defined as no viable tumor cell within all resected metastatic LNs. According to regression directionality, tumor regression pattern was summarized into four categories: type I, regression toward the lumen; type II, regression toward the invasive front; type III, concentric regression; and type IV, scattered regression. Inverse probability propensity score weighting was performed to minimize the influence of confounding factors.ResultsAfter adjusting for baseline characteristics, the R0 resection rates (90.9% vs. 89.0%, P=0.302) and pCR (ypT0N0) rates (29.8% vs. 34.0%, P=0.167) were comparable between two groups. Patients receiving NCRT showed lower TRG score (P<0.001) and higher major pathological response (MPR) rate (64.7% vs. 53.6%, P=0.001) compared to those receiving NICT. However, NICT brought a higher pCR rate of metastatic LNs than conventional NCRT (53.9% vs. 37.1%, P<0.001). The rates of type I/II/III/IV regression patterns were 44.6%, 6.8%, 11.4% and 37.1% in the NICT group, 16.9%, 8.2%, 18.3% and 56.6% in the NCRT group, indicating a significant difference (P<0.001). Moreover, there were no significant differences in the incidence of total postoperative complications (35.8% vs. 39.9%, P=0.189) and 30-d mortality (0.0% vs. 1.1%, P=0.062).ConclusionFor patients with locally advanced ESCC, NICT showed a R0 resection rate and pCR (ypT0N0) rate comparable to conventional NCRT, without increased incidence of postoperative complications and mortality. Notablely, NICT followed by surgery might bring a promising treatment response of metastatic LNs.

Background The relationship between cytokines and lung metastasis (LM) in breast cancer (BC) remains unclear and current clinical methods for identifying breast cancer lung metastasis (BCLM) lack precision, thus underscoring the need for an accurate risk prediction model. This study aimed to apply machine learning algorithms for identifying the key risk factors for BCLM before developing a reliable prediction model centered on cytokines. Methods This population-based retrospective study included 326 BC patients admitted to the Second Affiliated Hospital of Xuzhou Medical University between September 2018 and September 2023. After randomly assigning the patients to a training cohort (70%; n = 228) or a validation cohort (30%; n = 98) the risk factors for BCLM were identified using Least Absolute Shrinkage and Selection Operator (LASSO), Extreme Gradient Boosting (XGBoost) and Random Forest (RF) models. Significant risk factors were visualized with a Venn diagram and incorporated into a nomogram model, the performance of which was then evaluated according to three criteria, namely discrimination, calibration and clinical utility using calibration plots, receiver operating characteristic (ROC) curves and decision curve analysis (DCA). Results Among the cohort, 70 patients developed LM. A nomogram was then developed to predict the 5-year and 10-year BCLM risk by incorporating five key variables, namely endocrine therapy, hsCRP, IL6, IFN-ɑ and TNF-ɑ. For the 5-year prediction model, the training and validation cohorts had AUC values of 0.786 (95% CI: 0.691–0.881) and 0.627 (95% CI: 0.441–0.813), respectively, while for the 10-year prediction model, the corresponding AUC values were 0.687 (95% CI: 0.528–0.847) and 0.797 (95% CI: 0.605–0.988), respectively. ROC analysis further confirmed the model’s strong discriminative ability, while calibration plots indicated that the predicted and observed outcomes were in good agreement in both cohorts. Finally, DCA demonstrated the model’s effectiveness in clinical practice. Conclusion Using machine learning algorithms, this study developed aa nomogram that could effectively identify BC patients who were at a higher risk of developing LM, thus providing a valuable tool for decision-making in clinical settings.

Food safety is a major issue related to the vital interests of the people. In recent years, food safety incidents have emerged in an endless stream in China. However, the existing food safety traceability methods lack of data sharing, which makes it difficult to conduct unified supervision on food safety. In view of the problems existing in the current food safety traceability method, this paper introduces blockchain technology in food safety traceability field, selects milk as the object of food safety traceability in this paper, analyzes the whole process of milk supply chain, designs the overall framework of milk traceability scheme according to the demand analysis and design principles of milk safety traceability scheme, and designs the scheme's business function module, and chooses ECP-96 traceability coding scheme to ensure the uniqueness as well as security of milk traceability source. In view of the current application of blockchain technology, Hyperledger Fabric is creatively selected as the blockchain technology platform, and Go language is used to develop and implement the traceability method. Through the deployment of multiple nodes and functional testing, the expected food safety traceability goal is achieved.