Argininosuccinate lyase drives activation of mutant TERT promoter in glioblastomas.

Cancer-specific TERT promoter mutations have been linked to the reactivation of epigenetically silenced TERT gene by creating de novo binding motifs for E-Twenty-Six transcription factors, especially GABPA. How these mutations switch on TERT from epigenetically repressed states to expressed states have not been defined. Here, we revealed that EGFR activation induces ERK1/2-dependent phosphorylation of argininosuccinate lyase (ASL) at Ser417 (S417), leading to interactions between ASL and GABPA at the mutant regions of TERT promoters. The ASL-generated fumarate inhibits KDM5C, leading to enhanced trimethylation of histone H3 Lys4 (H3K4me3), which in turn promotes the recruitment of c-Myc to TERT promoters for TERT expression. Expression of ASL S417A, which abrogates its binding with GABPA, results in reduced TERT expression, inhibited telomerase activity, shortened telomere length, and impaired brain tumor growth in mice. This study reveals an unrecognized mechanistic insight into epigenetically activation of mutant TERT promoters where GABPA-interacted ASL plays an instrumental role.

SCG2 mediates blood-brain barrier dysfunction and schizophrenia-like behaviors after traumatic brain injury.

Traumatic brain injury (TBI), which is characterized by acute neurological dysfunction, is also one of the most widely recognized environmental risk factors for various neurological and psychiatric disorders. However, the role of TBI in neurological perturbation and the mechanisms underlying these disorders remain unknown. We evaluated transcriptional changes in cells of the frontal cortex after TBI by exploiting single-cell RNA sequencing (scRNA-Seq). We adopted the gene expression omnibus and scRNA-Seq to identify the mediation by secretogranin II (SCG2) of TBI-induced schizophrenia. Astrocytes are a principal source of SCG2 in the frontal cortex after TBI. Our analysis indicated that SCG2-triggered disruption of the blood-brain barrier (BBB) via the CypA-MMP-9 signaling pathway. Furthermore, astrocytic SCG2 knockout in the frontal cortex reduced BBB damage, mitigated inflammation, and inhibited schizophrenia after TBI. In conclusion, we identified the SCG2-CypA-MMP-9 signaling pathway in reactive astrocytes as a key switch in the protection of the BBB and provided a novel therapeutic avenue for treating psychiatric disorders after TBI.

Unlocking Synthesis of Polyhedral Oligomeric Silsesquioxane-Based Three-Dimensional Polycubane Covalent Organic Frameworks.

Reticular chemistry effectively yields porous structures with distinct topological lattices for a broad range of applications. Polyhedral oligomeric silsesquioxane (POSS)-based octatopic building blocks with a rare Oh symmetric configuration and attracting inorganic features have great potential for creating three-dimensional (3D) covalent organic frameworks (COFs) with new topologies. However, the intrinsic flexibility and intensive motion of cubane-type POSS molecules make the construction of 3D regular frameworks challenging. Herein, by fastening three or four POSS cores with per aromatic rigid linker from rational steric directions, we successfully developed serial crystalline 3D COFs with unpresented "the" and scu topologies. Both the experimental and theoretical results proved the formation of target 3D POSS-based COFs. The resultant hybrid networks with designable chemical skeletons and high surface areas maintain the superiorities of both the inorganic and organic components, such as their high compatibility with inorganic salts, abundant periodic electroactive sites, excellent thermal stability, and open multilevel nanochannels. Consequently, the polycubane COFs could serve as outstanding solid electrolytes with a high ionic conductivity of 1.23 × 10-4 S cm-1 and a lithium-ion transference number of 0.86 at room temperature. This work offers a pathway to generate ordered lattices with multiconnected flexible cube motifs and enrich the topologies of 3D COFs for potential applications.

Aprotic Lithium-Oxygen Batteries Based on Nonsolid Discharge Products.

Aprotic lithium-oxygen (Li-O2) batteries are considered to be a promising alternative option to lithium-ion batteries for high gravimetric energy storage devices. However, the sluggish electrochemical kinetics, the passivation, and the structural damage to the cathode caused by the solid discharge products have greatly hindered the practical application of Li-O2 batteries. Herein, the nonsolid-state discharge products of the off-stoichiometric Li1-xO2 in the electrolyte solutions are achieved by iridium (Ir) single-atom-based porous organic polymers (termed as Ir/AP-POP) as a homogeneous, soluble electrocatalyst for Li-O2 batteries. In particular, the numerous atomic active sites act as the main nucleation sites of O2-related discharge reactions, which are favorable to interacting with O2-/LiO2 intermediates in the electrolyte solutions, owing to the highly similar lattice-matching effect between the in situ-formed Ir3Li and LiO2, achieving a nonsolid LiO2 as the final discharge product in the electrolyte solutions for Li-O2 batteries. Consequently, the Li-O2 battery with a soluble Ir/AP-POP electrocatalyst exhibits an ultrahigh discharge capacity of 12.8 mAh, an ultralow overpotential of 0.03 V, and a long cyclic life of 700 h with the carbon cloth cathode. The manipulation of nonsolid discharge products in aprotic Li-O2 batteries breaks the traditional growth mode of Li2O2, bringing Li-O2 batteries closer to being a viable technology.

Anti-intercellular adhesion molecule 1 monomaintenance therapy induced long-term liver allograft survival without chronic rejection.

Calcineurin inhibitors (CNIs) are essential in liver transplantation (LT); however, their long-term use leads to various adverse effects. The anti-intercellular adhesion molecule (ICAM)-1 monoclonal antibody MD3 is a potential alternative to CNI. Despite its promising results with short-term therapy, overcoming the challenge of chronic rejection remains important. Thus, we aimed to investigate the outcomes of long-term MD3 therapy with monthly MD3 monomaintenance in nonhuman primate LT models. Rhesus macaques underwent major histocompatibility complex-mismatched allogeneic LT. The conventional immunosuppression group (Con-IS, n = 4) received steroid, tacrolimus, and sirolimus by 4 months posttransplantation. The induction MD3 group (IN-MD3, n = 5) received short-term MD3 therapy for 3 months with Con-IS. The maintenance MD3 group (MA-MD3, n = 4) received MD3 for 3 months, monthly doses by 2 years, and then quarterly. The MA-MD3 group exhibited stable liver function without overt infection and had significantly better liver allograft survival than the IN-MD3 group. Development of donor-specific antibody and chronic rejection were suppressed in the MA-MD3 group but not in the IN-MD3 group. Donor-specific T cell responses were attenuated in the MA-MD3 group. In conclusion, MD3 monomaintenance therapy without maintenance CNI provides long-term liver allograft survival by suppressing chronic rejection, offering a potential breakthrough for future human trials.

Hypercholesterolemia and the Increased Risk of Vascular Dementia: a Cholesterol Perspective.

PURPOSE OF REVIEW: Vascular dementia (VaD) is the second most prevalent type of dementia after Alzheimer's disease.Hypercholesterolemia may increase the risk of dementia, but the association between cholesterol and cognitive function is very complex. From the perspective of peripheral and brain cholesterol, we review the relationship between hypercholesterolemia and increased risk of VaD and how the use of lipid-lowering therapies affects cognition. RECENT FINDINGS: Epidemiologic studies show since 1980, non-HDL-C levels of individuals has increased rapidly in Asian countries.The study has suggested that vascular risk factors increase the risk of VaD, such as disordered lipid metabolism. Dyslipidemia has been found to interact with chronic cerebral hypoperfusion to promote inflammation resulting in cognitive dysfunction in the brain.Hypercholesterolemia may be a risk factor for VaD. Inflammation could potentially serve as a link between hypercholesterolemia and VaD. Additionally, the potential impact of lipid-lowering therapy on cognitive function is also worth considering. Finding strategies to prevent and treat VaD is critical given the aging of the population to lessen the load on society. Currently, controlling underlying vascular risk factors is considered one of the most effective methods of preventing VaD. Understanding the relationship between abnormal cholesterol levels and VaD, as well as discovering potential serum biomarkers, is important for the early prevention and treatment of VaD.

Biotransformation activities of fungal strain apiotrichum sp. IB-1 to ibuprofen and naproxen.

Ibuprofen (IBU) and naproxen (NPX), as widely prescribed non-steroidal anti-inflammatory drugs (NSAIDs), are largely produced and consumed globally, leading to frequent and ubiquitous detection in various aqueous environments. Previously, the microbial transformation of them has been given a little attention, especially with the isolated fungus. A yeast-like Apiotrichum sp. IB-1 has been isolated and identified, which could simultaneously transform IBU (5 mg/L) and NPX (2.5 mg/L) with maximum efficiencies of 95.77% and 88.31%, respectively. For mono-substrate, the transformation efficiency of IB-1 was comparable to that of co-removal conditions, higher than most of isolates so far. IBU was oxidized mainly through hydroxylation (m/z of 221, 253) and NPX was detoxified mainly via demethylation (m/z of 215) as shown by UPLC-MS/MS results. Based on transcriptome analysis, the addition of IBU stimulated the basic metabolism like TCA cycle. The transporters and respiration related genes were also up-regulated accompanied with higher expression of several dehydrogenase, carboxylesterase, dioxygenase and oxidoreductase encoding genes, which may be involved in the transformation of IBU. The main functional genes responsible for IBU and NPX transformation for IB-1 should be similar in view of previous studies, which needs further confirmation. This fungus would be useful for potential bioremediation of NSAIDs pollution and accelerate the discovery of functional oxidative genes and enzymes different from those of bacteria.

The development of a combined clinico-radiomics model for predicting post-operative recurrence in atypical meningiomas: a multicenter study.

PURPOSE: Atypical meningiomas could manifest early recurrence after surgery and even adjuvant radiotherapy. We aimed to construct a clinico-radiomics model to predict post-operative recurrence of atypical meningiomas based on clinicopathological and radiomics features. MATERIALS AND METHODS: The study cohort was comprised of 224 patients from two neurosurgical centers. 164 patients from center I were divided to the training cohort for model development and the testing cohort for internal validation. 60 patients from center II were used for external validation. Clinicopathological characteristics, radiological semantic, and radiomics features were collected. A radiomic signature was comprised of four radiomics features. A clinico-radiomics model combining the radiomics signature and clinical characteristics was constructed to predict the recurrence of atypical meningiomas. RESULTS: 1920 radiomics features were extracted from the T1 Contrast and T2-FLAIR sequences of patients in center I. The radiomics signature was able to differentiate post-operative patients into low-risk and high-risk groups based on tumor recurrence (P < 0.001). A clinic-radiomics model was established by combining age, extent of resection, Ki-67 index, surgical history and the radiomics signature for recurrence prediction in atypical meningiomas. The model achieved a good prediction performance with the integrated AUC of 0.858 (0.802-0.915), 0.781 (0.649-0.912) and 0.840 (0.747-0.933) in the training, internal validation and external validation cohort, respectively. CONCLUSIONS: The present study established a radiomics signature and a clinico-radiomics model with a favorable performance in predicting tumor recurrence for atypical meningiomas.

Molecular incompatibility between pig CD200 and human CD200 receptor in in vitro xenogeneic immune responses.

Overexpression of human CD200 (hCD200) in porcine endothelial cells (PECs) has been reported to suppress xenogeneic immune responses of human macrophages against porcine endothelial cells. The current study aimed to address whether the above-mentioned beneficial effect of hCD200 is mediated by overcoming the molecular incompatibility between porcine CD200 (pCD200) and hCD200 receptor or simply by increasing the expression levels of CD200 without any molecular incompatibility across the two species. We overexpressed hCD200 or pCD200 using lentiviral vectors with V5 marker in porcine endothelial cells and compared their suppressive activity against U937-derived human macrophage-like cells (hMCs) and primary macrophages. In xenogeneic coculture of porcine endothelial cells and human macrophage-like cells or macrophages, hCD200-porcine endothelial cells suppressed phagocytosis and cytotoxicity of human macrophages to a greater extent than pCD200-porcine endothelial cells. Secretion of tumor necrosis factor-α, interleukin-1ß, and monocyte chemoattractant protein-1 from human macrophages and expression of M1 phenotypes (inducible nitric oxide synthase, dectin-1, and CD86) were also suppressed by hCD200 to a greater extent than pCD200. Furthermore, in signal transduction downstream of CD200 receptor, hCD200 induced Dok2 phosphorylation and suppressed IκB phosphorylation to a greater extent than pCD200. The above data supported the possibility of a significant molecular incompatibility between pCD200 and human CD200 receptor, suggesting that the beneficial effects of hCD200 overexpression in porcine endothelial cells could be mediated by overcoming the molecular incompatibility across the species barrier rather than by simple overexpression effects of CD200.

Design, synthesis, and evaluation of benzodioxolane compounds for antitumor activity.

This study reports the design, synthesis, and comprehensive biological evaluation of 13 benzodioxolane derivatives, derived from the core structure of piperine, a natural product with established antitumor properties. Piperine, primarily found in black pepper, has been noted for its diverse pharmacological activities, including anti-inflammatory, antioxidant, and anticancer effects. Leveraging piperine's antitumor potential, we aimed to enhance its efficacy through structural modifications. Among the synthesized compounds, HJ1 emerged as the most potent, exhibiting a 4-fold and 10-fold increase in inhibitory effects on HeLa and MDA-MB-231 cell lines, respectively, compared to piperine. Furthermore, HJ1 demonstrated a favorable safety profile, characterized by significantly lower cytotoxicity towards the human normal cell line 293T. Mechanistic investigations revealed that HJ1 markedly inhibited clonogenicity, migration, and adhesion of HeLa cells. In vivo studies utilizing the chick embryo chorioallantoic membrane (CAM) model substantiated the robust antitumor activity of HJ1, evidenced by its ability to suppress tumor angiogenesis and reduce tumor weight. These results suggest that HJ1 holds significant promise as a lead compound for the development of novel antitumor therapies.

Design, synthesis and antitumor activity of novel 4-oxobutanamide derivatives.

To find highly effective and low-toxicity antitumor drugs to overcome the challenge of cancer, we designed and synthesized a series of novel 4-oxobutanamide derivatives using the principle of molecular hybridization and tested the antiproliferative ability of the title compounds against human cervical carcinoma cells (HeLa), human breast carcinoma cells (MDA-MB-231) and human kidney carcinoma cells (A498). Among them, N1-(4-methoxybenzyl)-N4-(4-methoxyphenyl)-N1-(3,4,5-trimethoxyphenyl) succinimide DN4 (IC50 = 1.94 µM) showed the best proliferation activity on A498, superior to the positive control paclitaxel (IC50 = 8.81 µM) and colchicine (IC50 = 7.17 µM). Compound DN4 not only inhibited the proliferation, adhesion and invasion of A498, but also inhibited angiogenesis and tumor growth in a dose-dependent manner in the xenograft model of A498 cells. In addition, we also predicted the physicochemical properties and toxicity (ADMET) of these derivatives, and the results suggested that these derivatives may have the absorption, distribution, metabolism, excretion, and toxicity properties of drug candidates. Thus, compound DN4 may be a promising drug candidate for the treatment of cancer.

Resistant Dextrin Protects Rats Against Streptozotocin Induced Gestational Diabetes Mellitus via Alteration of TLR4/MyD88/NF-κB Signaling Pathway.

Objective: Gestational diabetes mellitus (GDM) is a metabolic disorder that occurs in 3-5% of pregnancies. The inflammatory response is essential to the development of GDM. Resistant dextrin is a natural fiber and exhibits an antidiabetic effect against diabetes. We investigate resistant dextrin's preventive role and underlying mechanism against STZ-induced GDM. Material and method: Female Wistar rats were utilized, and GDM was induced in pregnant rats using STZ. The levels of glycated hemoglobin (HbA1c), resistin, serum-c-peptide, free fatty acid, antioxidant, hepatic glycogen, lipid, inflammatory cytokines, apoptosis, and inflammatory parameters were estimated. mRNA expression of Toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), nuclear factor kappa B (NF-κB) and NOD-like receptor protein 3 (NLRP3) was estimated. We also estimated the histopathology of pancreatic and liver tissue. Result: Body weight, plasma insulin, fetal body weight, and blood glucose levels were all considerably (P < .001) improved by resistant dextrin, while placental weight and blood sugar levels were also decreased. Resistant dextrin significantly (P < .001) suppressed the levels of HbA1c, resistin, serum-c-peptide, and hepatic glycogen and improved the free fatty acid (FFA) level. Resistant dextrin significantly (P < .001) altered the level of adiponectin, leptin, intercellular Adhesion Molecule 1 (ICAM-1), and visfatin; antioxidant parameters such as malonaldehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx), glutathione S-transferase GST, inflammatory cytokines like tumor necrosis factor- α (TNF-α), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-2 (IL-2), interferon- γ (INF-γ), interleukin-10 (IL-10); apoptosis parameters include Bcl-2, caspase-3, and Bax, respectively. Resistant dextrin significantly (P < .001) suppressed the mRNA expression of NF-κB, MyD88, NLRP3, and TLR4. Resistant dextrin altered the histopathological changes in the pancreas and hepatic tissue. Discussion and Conclusion: In short, resistant dextrin demonstrated a protective effect against STZ-induced GDM by modulating the TLR4/MyD88/NF-κB signaling pathway.

miR-145a-5p/SIK1/cAMP-dependent alteration of synaptic structural plasticity drives cognitive impairment induced by coke oven emissions.

Exposure to fine particulate matter (PM) is associated with the neurodegenerative diseases. Coke oven emissions (COEs) in occupational environment are important sources of PM. However, its neurotoxicity is still unclear. Therefore, evaluating the toxicological effects of COE on the nervous system is necessary. In the present study, we constructed mouse models of COE exposure by tracheal instillation. Mice exposed to COE showed signs of cognitive impairment. This was accompanied by a decrease in miR-145a-5p and an increase in SIK1 expression in the hippocampus, along with synaptic structural damage. Our results demonstrated that COE-induced miR-145a-5p downregulation could increase the expression of SIK1 and phosphorylated SIK1, inhibiting the cAMP/PKA/CREB pathway by activating PDE4D, which was associated with reduced synaptic structural plasticity. Furthermore, restoring of miR-145a-5p expression based on COE exposure in HT22 cells could partially reversed the negative effects of COE exposure through the SIK1/PDE4D/cAMP axis. Collectively, our findings link epigenetic regulation with COE-induced neurotoxicity and imply that miR-145a-5p could be an early diagnostic marker for neurological diseases in patients with COE occupational exposure.

Developmental 6:2 FTCA exposure impairs renal development in chicken embryos via IGF signaling.

6:2 fluorotelomer carboxylic acid (6:2 FTCA) is a perfluorooctanoic acid (PFOA) substitute, which is supposedly less accumulative and toxic than PFOA. However, 6:2 FTCA is structurally similar to PFOA, and there had already been reports about its toxicities comparable to PFOA. The aim of the current study is to assess potential effects of developmental exposure to 6:2 FTCA on the development of kidney in chicken embryo and to investigate underlying mechanism. Fertile chicken eggs were exposed to 1.25 mg/kg, 2.5 mg/kg or 5 mg/kg doses of 6:2 FTCA, or 2 mg/kg PFOA, then incubated to hatch. Serum and kidney of hatchling chickens were collected. Blood urea nitrogen (BUN) and creatinine (Cre) levels were measured with commercially available kits. Morphology of kidney was assessed with histopathology. To further reveal molecular mechanism of observed endpoints, IGF signaling molecules were assessed in the kidney samples with qRT-PCR, results indicated that IGFBP3 is a potentially crucial molecule. Lentiviruses overexpressing or silencing IGFBP3 were designed and applied to enhance/suppress the expression of IGFBP3 in developing chicken embryo for further verification of its role in the observed effects. Disrupted nephron formation, in the manifestation of decreased glomeruli number/area and increased serum BUN/Cre levels, was observed in the animals developmentally exposed to 6:2 FTCA. Correspondingly, IGF signaling molecules (IGF1, IGF1R and IGFBP3) were affected by 6:2 FTCA exposure. Meanwhile, overexpression of IGFBP3 effectively alleviated such changes, while silencing of IGFBP3 mimicked observed effects. In conclusion, developmental exposure to 6:2 FTCA is associated with disrupted chicken embryo renal development, in which IGFBP3 seems to be a remarkable contributor, suggesting potential health risks for human and other species. Further risk assessments and mechanistic works are necessary.

First Report of the Rust Fungus Melampsora ferrinii on Salix babylonica in China and a New Spermogonial and Aecial Host, Corydalis bungeana.

The occurrence of rust fungi on Corydalis bungeana Turcz. and Salix babylonica L. were found in same area of Hebei Province, China from 2022 to 2023. The life cycle connection of these rust fungi was suspected because Peng et al. (2022) reported the life cycle of Melampsora ferrinii Toome & Aime by inoculations, producing spermogonia and aecia on Corydalis species, and uredinia on S. babylonica. The morphology of the uredinial and telial stages on S. babylonica collected in the field was identical with the description of M. ferrinii by Toome and Aime (2015), and its identity was confirmed by phylogenetic analyses using the method of Ji et al. (2020) (LSU-PP087777, ITS-PP091274; Similarity with M. ferrinii: LSU-100%, ITS-99.85%). To confirm the life cycle of this rust fungus, inoculations were conducted on C. bungeana with basidiospores obtained from the teliospores on fallen leaves of Salix babylonica. The fallen leaves producing basidiospores were cut into small pieces (ca. 5 mm2) and placed on healthy leaves of C. bungeana. The inoculated plants were kept in a moist plastic box in darkness at 15-20℃ for 2 days and then transferred to the floor near windows at about 15-20℃ for observations. Ten days after inoculations small yellow spots of spermogonia appeared on the upper surface of the leaves of C. bungeana. About 7 days later, pale yellow aecia with aeciospores were produced mainly on the under surface of the leaves and petioles. The morphology of rust fungus on C. bungeana collected from the fields and obtained by inoculations was identical with the description by Peng et al. (2022). Phylogenetic analyses also showed that a specimen on C. bungeana collected from the field (LSU-OR607838, ITS-OR612063) were included into the same clade of M. ferrinii (Similarity: LSU-100 %, ITS-99.85). Based on morphology, inoculations and DNA sequence analyses, the rust fungi on C. bungeana and S. babylonica are identified as different stages of life cycle of M. ferrinii. This rust fungus has been reported to produce spermogonia and aecia on C. acuminata Franch., C. edulis Maxim. and C. racemosa (Thunb.) Pers. in China (Peng et al. 2022), and uredinia and telia on S. babylonica in USA, Argentina and Iran (Toome and Aime 2015, Abbasi et al. 2024), and on Salix sp. in Chile (Zapata 2016). Therefore, C. bungeana is a new host for M. ferrinii, and its field occurrence on S. babylonica is reported for the first time in China although Peng et al. (2022) reported successful results in its inoculations to S. babylonica in China. This report contributes to the control of rust diseases caused by this species. Specimens used in this experiment were deposited in the Fungal Herbarium of the Jilin Agricultural University, Changchun, China (HMJAU) and sequences newly analyzed were deposited in GenBank.

Modifiable risk factors mediate the effect of gastroesophageal reflux disease on stroke and subtypes: A Mendelian randomization study.

OBJECTIVES: Previous observational studies have suggested that gastroesophageal reflux disease (GERD) increases the risk of stroke, but the specific underlying mechanisms are unclear. We investigated the causal associations of GERD with stroke and its subtypes using Mendelian randomization (MR), and evaluated the potential mediating effects of modifiable stroke risk factors in the causal pathway. METHODS: Genetic instrumental variables for GERD were extracted from the latest genome-wide association study (GWAS) summary level data. We initially performed two-sample MR to examine the association of GERD with stroke and its subtypes, including ischemic stroke, intracranial hemorrhage, and the major subtypes of ischemic stroke. Two-step MR was further employed to investigate the mediating effect of 15 risk factors in the causal pathway. RESULTS: We found significant causal associations of genetically predicted GERD with increased risk of stroke (OR: 1.22 95% CI: 1.126-1.322), ischemic stroke (OR: 1.19 95% CI: 1.098-1.299), and large-artery stroke (OR: 1.49 95% CI: 1.214-1.836). Replication and sensitivity analyses yielded consistent effect directions and similar estimates. Further mediation analyses indicated that hypertension (HTN), systolic blood pressure (SBP), and type 2 diabetes (T2D) mediated 36.0%, 9.0%, and 15.8% of the effect of GERD on stroke; 42.9%, 10.8%, and 21.4% for ischemic stroke, and 23.3%; 7.9%, and 18.7% for large-artery stroke, respectively. CONCLUSIONS: This study supports that GERD increases susceptibility to stroke, ischemic stroke, and large-artery stroke, and is partially mediated by HTN, SBP, and T2D.

Association of sleep characteristics with stroke incidence and all-cause mortality: A cross-sectional study in the United States.

BACKGROUND: Stroke represents a significant health crisis in the United States, claiming approximately 140,000 lives annually and ranking as the fifth leading cause of death. OBJECTIVE: Utilizing data from the National Health and Nutrition Examination Survey (NHANES) for 2005 to 2008, this study examines the correlation between various sleep characteristics and both stroke morbidity and all-cause mortality among U.S. adults. METHODS: We applied logistic regression, Cox regression, and subgroup analyses to a sample of 7,827 adults aged 18 and older from NHANES 2005-2008. The study focused on six sleep characteristics: duration of sleep, sleep onset latency, snoring frequency, number of awakenings, frequency of leg spasms during sleep, and daytime sleepiness, analyzing their impacts on stroke incidence and mortality rates. RESULTS: Participants had an average age of 45.80 ± 0.45 years, with females accounting for 48.13 % of the sample. Analysis revealed significant associations between sleep duration, onset latency, number of awakenings, leg spasms, and daytime sleepiness with stroke incidence. However, these associations weakened with increasing confounders. Additionally, stroke patients showed a higher likelihood of using sleep aids. The influence of sleep disturbances on stroke appeared more pronounced in females and younger demographics. An association was also noted between the number of awakenings, sleep duration, and stroke mortality rates CONCLUSIONS: The study reinforces the critical role of maintaining healthy sleep patterns in preventing strokes and enhancing stroke prognosis, emphasizing specific sleep disturbances as potential risk factors.

Comprehensive Evaluation of Quality and Differences in Silene viscidula Franch from Different Origins Based on UPLC-ZENO-Q-TOF-MS/MS Compounds Analysis and Antioxidant Capacity.

Silene viscidula Franch is mainly produced in southwest China. The region has a vast area and rich climate, which has an impact on the quality of the plants due to the differences in distribution between the origins. There is a lack of systematic research on its chemical compounds in the existing literature, and fewer studies have been reported for the active compounds of this plant. Therefore, high-resolution liquid mass spectrometry was used in this study. Sixty batches of Silene viscidula Franch samples from twenty origins in three provinces were analyzed for compounds. A database of chemical compounds of Silene viscidula Franch was established through node-to-node information in the GNPS molecular network, as well as literature records. The ion fragmentation information obtained was compared with the literature data and analyzed and identified by importing the mass spectrometry software PeakView 1.2. Then, the MarkerView t-test was applied to analyze and identify the compounds of Silene viscidula Franch from different origins. Afterwards, the antioxidant activity of Silene viscidula Franch from different origins was preliminarily evaluated using DPPH and ABTS free radical scavenging assays. The results showed a total of 78 compounds, including 34 steroids, 14 triterpenoid saponins, 30 flavonoid glycosides, and other classes of compounds, such as alkaloids. The cleavage patterns of steroids, triterpenoid saponins, and flavonoids in positive-ion mode were also summarized. Based on the p-value of the t-test (p < 0.05), 29 differential compounds were screened out. The relative contents of saponins and steroidal compounds in these samples were found to be associated with antioxidant activity. This study provided a preliminary reference for the establishment of a comprehensive evaluation system for the quality of Silene viscidula Franch.

Rapid Analysis of Compounds from Piperis Herba and Piperis Kadsurae Caulis and Their Differences Using High-Resolution Liquid-Mass Spectrometry and Molecular Network Binding Antioxidant Activity.

There is a serious mixing of Piperis Herba and Piperis Kadsurae Caulis in various parts of China due to the similar traits of lianas, and there is a lack of systematic research on the compound and activity evaluation of the two. Likewise, the differences in compounds brought about by the distribution of origin also need to be investigated. In this study, high-resolution liquid-mass spectrometry (UPLC-Q-Zeno-TOF-MS/MS) was used to analyze samples of Piperis Herba from five origins and Piperis Kadsurae Caulis from five origins, with three batches collected from each origin. The compounds were identified based on precise molecular weights, secondary fragments, and an online database combined with node-to-node associations of the molecular network. The t-test was used to screen and analyze the differential compounds between the two. Finally, the preliminary evaluation of antioxidant activity of the two herbs was carried out using DPPH and ABTS free radical scavenging assays. The results showed that a total of 72 compounds were identified and deduced in the two Chinese medicines. These compounds included 54 amide alkaloids and 18 other compounds, such as flavonoid glycosides. The amide alkaloids among them were then classified, and the cleavage pathways in positive ion mode were summarized. Based on the p-value of the t-test, 32 differential compounds were screened out, and it was found that the compounds of Piperis Herba were richer and possessed a broader spectrum of antioxidant activity, thus realizing a multilevel distinction between Piperis Herba and Piperis Kadsurae Caulis. This study provides a preliminary reference for promoting standardization and comprehensive quality research of the resources of Piperis Herba using Piperis Kadsurae Caulis as a reference.