Pyrosequencing analysis of IRS1 methylation levels in schizophrenia with tardive dyskinesia

Tardive dyskinesia (TD) is a serious side effect of certain antipsychotic medications that are used to treat schizophrenia (SCZ) and other mental illnesses. The methylation status of the insulin receptor substrate 1 (IRS1) gene is reportedly associated with SCZ; however, no study, to the best of the authors\u27 knowledge, has focused on the quantitative DNA methylation levels of the IRS1 gene using pyrosequencing in SCZ with or without TD. The present study aimed to quantify DNA methylation levels of 4 CpG sites in the IRS1 gene using a Chinese sample including SCZ patients with TD and without TD (NTD) and healthy controls (HCs). The general linear model (GLM) was used to detect DNA methylation levels among the 3 proposed groups (TD vs. NTD vs. HC). Mean DNA methylation levels of 4 CpG sites demonstrated normal distribution. Pearson\u27s correlation analysis did not reveal any significant correlations between the DNA methylation levels of the 4 CpG sites and the severity of SCZ. GLM revealed significant differences between the 3 groups for CpG site 1 and the average of the 4 CpG sites (P=0.0001 and P=0.0126, respectively). Furthermore, the TD, NTD and TD + NTD groups demonstrated lower methylation levels in CpG site 1 (P=0.0003,

Hamiltonicity in 2-connected graphs with claws

AbstractMatthews and Sumner have proved in [12] that if G is a 2-connected claw-free graph of order n such that δ ⩾ (n − 2)/3, then G is hamiltonian. Li has shown that the bound for the minimum degree δ can be reduced to n/4 under the additional condition that G is not in Π, where Π is a class of graphs defined in [7]. On the other hand, we say that a graph G is almost claw-free if the centres of induced claws are independent and their neighbourhoods are 2-dominated. Broersma, Ryjáček and Schiermeyer have proved that if G is 2-connected almost claw-free graph of order n such that δ ⩾ (n − 2)/3, then G is hamiltonian. We generalize these results by considering the graphs whose claw centres are independent. If G is a 2-connected graph of order n and minimum degree δ such that n ⩽ 4δ − 3 and if the set of claw centres of G is independent, then we show that either G is hamiltonian or G ϵ F, where F is a class of graphs defined in the paper. The bound n ⩽ 4δ − 3 is sharp

Lipid-Based Nanotechnology: Liposome

Over the past several decades, liposomes have been extensively developed and used for various clinical applications such as in pharmaceutical, cosmetic, and dietetic fields, due to its versatility, biocompatibility, and biodegradability, as well as the ability to enhance the therapeutic index of free drugs. However, some challenges remain unsolved, including liposome premature leakage, manufacturing irreproducibility, and limited translation success. This article reviews various aspects of liposomes, including its advantages, major compositions, and common preparation techniques, and discusses present U.S. FDA-approved, clinical, and preclinical liposomal nanotherapeutics for treating and preventing a variety of human diseases. In addition, we summarize the significance of and challenges in liposome-enabled nanotherapeutic development and hope it provides the fundamental knowledge and concepts about liposomes and their applications and contributions in contemporary pharmaceutical advancement

Active distribution network fault section location method based on characteristic wave coupling

Abstract As distributed generators (DG) and power electronic devices become more integrated, distribution networks have evolved from being passive to active, and power flow has shifted from unidirectional to bidirectional. This transformation has negatively impacted power quality, leading to weakened fault transient attributes and increased harmonic complexities. Consequently, the efficacy of traditional relay protection has diminished, elevating the risk of misoperation or misjudgment and compromising the safety of distribution networks. In response to these challenges, a fault section location method for active distribution network based on characteristic wave coupling is proposed to expand the fault difference. This method explores the principles of characteristic wave coupling, discusses characteristic wave parameter selection theory, examines the start‐up control strategy for characteristic wave coupling, and establishes a protection action criterion by comparing the energy difference of characteristic waves based on the fault identification principle. Subsequently, by utilizing multiple inverter interfaced distributed generators to actively couple characteristic waves into the distribution network during faults, achieves rapid identification and location of fault sections. Finally, the effectiveness of the method is substantiated through simulation results in MATLAB/Simulink and experimental outcomes obtained from a low‐voltage active distribution network experimental platform based on dSPACE1103

Camptothesome Potentiates PD-L1 Immune Checkpoint Blockade for Improved Metastatic Triple-Negative Breast Cancer Immunochemotherapy

In this study, we focus on investigating the therapeutic effects of camptothesome on treating metastatic triple-negative breast cancer (TNBC). We elucidate that camptothesome elicited stronger immunogenic cell death (ICD) compared to free camptothecin (CPT) and Onivyde in 4T1 TNBC cells. In addition, camptothesome is mainly internalized by the 4T1 and MDA-MB-231 cells through clathrin-mediated endocytosis based on the results of flow cytometry. Through real-time Lago optical imaging, camptothesome shows excellent tumor-targeting efficiency in orthotopic TNBC tumors. We demonstrate that camptothesome can upregulate programmed death-ligand 1 (PD-L1) in 4T1 tumors in an interferon gamma (IFN-γ)-dependent manner. Furthermore, the anti-TNBC efficacy studies reveal that camptothesome is superior to Onivyde and markedly potentiates PD-L1 immune checkpoint blockade therapy with complete lung metastasis remission in an orthotopic 4T1-Luc2 tumor model. This combination therapy eliciting robust cytotoxic T lymphocytes (CTL) response via boosting tumor-infiltrating cluster of differentiation 8 (CD8), calreticulin (CRT), high mobility group box 1 protein (HMGB-1), low-density lipoprotein receptor-related protein 1 (LRP1), IFN-γ, and granzyme B. Our work corroborates the promise of camptothesome in favorably modulating tumor immune microenvironment via inducing ICD to fortify the PD-L1 checkpoint blockade therapy for improved treatment of intractable TNBC

Effect of the internet combined with exercise-based individualized nursing intervention in patients with gestational diabetes mellitus

Abstract Background Gestational diabetes mellitus (GDM) is the most frequent medical complication of pregnancy. This condition is manifested by glucose intolerance resulting in hyperglycemia of variable severity during pregnancy. One of the most important clinical tools for efficiently regulating maternal blood glucose is strictly monitoring blood glucose levels. However, due to a lack of appropriate intervention tools, managing the occurrence of GDM is still unfeasible. This study aimed to determine clinical efficacy of the internet combined with exercise-based individualized nursing intervention in patients with gestational diabetes mellitus (GDM). Methods In total, 139 patients with GDM were divided into two groups, with 79 patients in the observation group (internet combined with exercise-based individualized nursing intervention) and 60 patients in the control group (routine nursing intervention only). The two groups were given specified nursing intervention for 8 weeks and then compared for changes in their blood glucose, blood lipids, blood pressure, insulin resistance (IR), and rate of adverse pregnancy outcomes. Additionally, the psychological state was analyzed, and their nursing satisfaction with the care from nurses that they received was investigated before and after the nursing intervention. Results Compared with the control group, the following indices of the observation group were lowered: blood glucose-related indices (FBG and 2 h PG), blood lipids and blood pressure associated indices (TG, TC, and HbA1c, DBP, SBP, and MAP), and IR-related indices (FINS, 2 h INS, and HOMA -IR) (all P &lt; 0.05). The observation group also showed a lower rate of adverse pregnancy outcomes than the control group (7.59% vs. 20.00%; P &lt; 0.05). In addition, SAS and SDS scores of the observation group were both lower than the control group (P &lt; 0.05). Accordingly, the nursing satisfaction score also displayed that the observation group (93.67%) had a higher satisfaction outcome than the control group (76.67%; P &lt; 0.05). Conclusions Internet combined with exercise-based individualized nursing intervention in GDM patients can effectively improve their blood glucose, IR, and psychological status, thus significantly improving their pregnancy outcomes and mental condition. </jats:sec