Search

Abstract Background Human patients often experience an episode of serious seizure activity, such as status epilepticus (SE), prior to the onset of temporal lobe epilepsy (TLE), suggesting that SE can trigger the development of epilepsy. Yet, the underlying mechanisms are not fully understood. The low-density lipoprotein receptor related protein (Lrp4), a receptor for proteoglycan-agrin, has been indicated to modulate seizure susceptibility. However, whether agrin-Lrp4 pathway also plays a role in the development of SE-induced TLE is not clear. Methods Lrp4 f/f mice were crossed with hGFAP-Cre and Nex-Cre mice to generate brain conditional Lrp4 knockout mice (hGFAP-Lrp4 −/− ) and pyramidal neuron specific knockout mice (Nex-Lrp4 −/− ). Lrp4 was specifically knocked down in hippocampal astrocytes by injecting AAV virus carrying hGFAP-Cre into the hippocampus. The effects of agrin-Lrp4 pathway on the development of SE-induced TLE were evaluated on the chronic seizure model generated by injecting kainic acid (KA) into the amygdala. The spontaneous recurrent seizures (SRS) in mice were video monitored. Results We found that Lrp4 deletion from the brain but not from the pyramidal neurons elevated the seizure threshold and reduced SRS numbers, with no change in the stage or duration of SRS. More importantly, knockdown of Lrp4 in the hippocampal astrocytes after SE induction decreased SRS numbers. In accord, direct injection of agrin into the lateral ventricle of control mice but not mice with Lrp4 deletion in hippocampal astrocytes also increased the SRS numbers. These results indicate a promoting effect of agrin-Lrp4 signaling in hippocampal astrocytes on the development of SE-induced TLE. Last, we observed that knockdown of Lrp4 in hippocampal astrocytes increased the extracellular adenosine levels in the hippocampus 2 weeks after SE induction. Blockade of adenosine A1 receptor in the hippocampus by DPCPX after SE induction diminished the effects of Lrp4 on the development of SE-induced TLE. Conclusion These results demonstrate a promoting role of agrin-Lrp4 signaling in hippocampal astrocytes in the development of SE-induced development of epilepsy through elevating adenosine levels. Targeting agrin-Lrp4 signaling may serve as a potential therapeutic intervention strategy to treat TLE.

AbstractZanthoxylum ailanthoides is a deciduous tree, with important medicinal and economic values. The complete chloroplast genome sequence of Z. ailanthoides was assembled and the phylogenetic relationship to other species was inferred in this study. The chloroplast genome is 157,209 bp in length, including two inverted repeats of 26,408 bp, a large single-copy of 86,099 bp and a small single copy of 18,294 bp. Moreover, the chloroplast genome contains 129 genes, including 84 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. The overall GC content of the chloroplast genome is 38.4%. The phylogenetic analysis indicated that Z. ailanthoides was grouped with a clade containing the species of Z. multijugum, Z. calcicola, Z. oxyphyllum, Z. stenophyllum, and the genus was closely related to Phellodendron. This study contributes to a better understanding of the phylogenetic relationships among Zanthoxylum species.

Objectives: Health education may improve health in geriatric patients. To evaluate differences between remote and in-person education, the DREAMS ("'D'eveloping a 'R'esearch Participation 'E'nhancement and 'A'dvocacy Training Progra'm' for Diverse 'S'eniors") health seminar series compared in-person and remote learning groups to assess feasibility, satisfaction, adherence, health literacy, and cognitive outcomes. Research Design: Nonrandomized two-arm interventions occurred remotely or in-person. About 130 diverse, older adults (M age: 70.8 ± 9.2 years; in-person n = 95; remote, n = 35) enrolled. Data from 115 completers (In-person n = 80; Remote n = 35) were analyzed for performance outcomes. Feasibility, adherence, and satisfaction benchmarks were evaluated at baseline, immediately post intervention, and 8 weeks post intervention. Adjusting for baseline performances, outcomes on health literacy and cognitive measures were compared between groups after intervention (at posttest and at 8-week follow-up) using adjusted mean differences ([beta] coefficients). Results: Eighty in-person and all remote participants completed at least six modules. Both programs had high satisfaction, feasibility, and strong adherence. After adjusting for demographic covariates and baseline values, cognitive and motor cognitive measures between groups were domain specific (e.g., global cognition, executive function, spatial memory, mental tracking capacity, and cognitive integration). Discussion and Implications: This work explores feasible measures of knowledge acquisition and its link to health literacy and cognitive outcomes. Identifying effective delivery methods may increase involvement in clinical research. Future studies may encourage remote learning for increased accessibility.

Background: Bisphenol A (BPA) is an industrial chemical that is commonly found in daily consumer products. BPA is reportedly associated with lung diseases. However, the impact of BPA on pulmonary fibrosis (PF) and its possible mechanisms of action both remain unclear. Methods: A PF mouse model was induced by bleomycin (BLM). Mouse lung fibroblasts (MLG 2908) and mouse alveolar epithelial cells (MLE-12) were treated with BPA to establish a PF cell model. Tissue staining, CCK-8 assays, western blot experiments and relevant indicator kits were used to detect and evaluate the effect of BPA on PF. Results: BPA dose-dependently promoted oxidative stress and induced ferroptosis, leading to PF. The ferroptosis inhibitor Fer-1 partly attenuated the effect of BPA. In addition, among the two main cell types associated with the progression of PF, MLE-12 cells are more sensitive to BPA than are MLG 2908 cells, and BPA induces ferroptosis in MLE-12 cells. Furthermore, BPA promoted autophagy-mediated ferroptosis by activating the AMPK/mTOR signaling pathway, thereby exacerbating the progression of PF. The autophagy inhibitor CQ1 partly attenuated the effect of BPA. Conclusion: BPA promotes the progression of PF by promoting autophagy-dependent ferroptosis in alveolar epithelial cells, which provides a new theoretical basis for understanding BPA-induced PF.

Liupao tea is one of the well-known Chinese tea brands and a famous local specialty in Wuzhou, Guangxi, China. However, the genetic background and phylogenetic relationship of the native resource plants of Liupao tea need study, especially at the genomic level. In this study, we reported the complete chloroplast (cp) genome sequence of Camellia sinensis var. sinensis cultivar ‘Liupao’ (LP, Liupao tea population) and inferred its phylogenetic relationship to other tea plant variants or cultivars. The cp genome had a total length of 157,097 bp and the overall GC content was 37.3%. The cp genome contained one LSC region (86,641 bp) and one SSC region (18,276 bp), which were separated by two IR regions (26,090 bp, respectively). Moreover, the cp genomes were composed of 130 genes, including 86 protein-coding genes, 36 tRNA genes, and eight rRNA genes. The phylogenetic analysis showed that LP was closely related to C. sinensis var. pabilimba cv. ‘Lingyunbaihao’. This study will provide useful information for further investigating the genetic background, evolution, and breeding of LP as well as other tea cultivars and varieties.

Abstract Background and purpose The heterogeneous, complex condition known as ischemic stroke (IS) is brought on by the interaction of a number of risk factors and genetic variables. The association between C‐reactive protein (CRP) gene polymorphisms and IS has, however, been the subject of inconsistent findings. Therefore, we conducted a meta‐analysis to comprehensively address possible associations of CRP genes with the risk of IS. Methods A comprehensive literature search for all the published articles was performed in electronic databases including PubMed, EMBASE, Cochrane Library, and Google Scholar from January 1, 1950 to June 30, 2022. Odds ratio (OR) with 95% Confidence interval (CIs) along with fixed/random effect models were used to calculate summary estimates. Results Twelve case‐control studies totalling 3880 IS cases and 5233 controls were included for the association of CRP gene polymorphisms (rs1800947, rs1130864, rs3093059, rs2794521, and rs1205). Across all genotyping models, we discovered that rs1130864, rs3093059, rs2794521, and rs1205SNPs were not substantially related to IS risk. A trend for significant association for rs1800947 under dominant (OR = 1.19; 95% CI = 0.97 to 1.48), recessive (OR = 1.49; 95% CI = 0.71 to 3.14) and allelic model (OR = 1.21; 95% CI = 0.99 to 1.48) was observed. However, protective association for rs1130864 under dominant (OR = 0.80; 95% CI = 0.70 to 0.91) and rs3093059 under allelic model (OR = 0.18; 95% CI = 0.14 to 0.22) was found. Conclusion Our thorough study revealed that the CRP gene variants rs1800947, rs1130864, rs3093059, rs2794521, and rs1205 could not be related to the risk of ischemic stroke. However, additional research must focus on the rs1800947 polymorphisms in a particular group.

Several commonly used opioid analgesics, such as fentanyl, sufentanil, alfentanil, and hydrocodone, are by report primarily metabolized by the CYP3A4 enzyme. The concurrent use of ritonavir, a potent CYP3A4 inhibitor, can lead to significant drug interactions. Using physiologically based pharmacokinetic (PBPK) modeling and simulation, this study examines the effects of different dosing regimens of ritonavir on the pharmacokinetics of these opioids. The findings reveal that co-administration of ritonavir significantly increases the exposure of fentanyl analogs, with over a 10-fold increase in the exposure of alfentanil and sufentanil when given with ritonavir. Conversely, the effect of ritonavir on fentanyl exposure is modest, likely due to additional metabolism pathways. Additionally, the study demonstrates that the steady-state exposure of hydrocodone and its active metabolite hydromorphone can be increased by up to 87% and 95%, respectively, with concurrent use of ritonavir. The extended-release formulation of hydrocodone is particularly affected. These insights from PBPK modeling provide valuable guidance for optimizing opioid dosing and minimizing the risk of toxicity when used in combination with ritonavir-containing prescriptions. [ABSTRACT FROM AUTHOR]

Mucormycosis caused by Lichtheimia ramosa is an emerging and uncommon opportunistic infection in patients with hematological malignancies, with high mortality rates. Herein, we first report a case of pulmonary mucormycosis with Lichtheimia ramosa in a 3-year-old girl recently diagnosed with B-cell acute lymphoblastic leukemia. The diagnosis was made using computerized tomography of the lung, metagenomic next-generation sequencing (mNGS) of blood and sputum specimens, and microscopic examination to detect the development of Lichtheimia ramosa on the surgical specimen. She was effectively treated after receiving prompt treatment with amphotericin B and posaconazole, followed by aggressive surgical debridement. In our case, the fungal isolates were identified as Lichtheimia ramosa using mNGS, which assisted clinicians in quickly and accurately diagnosing and initiating early intensive treatment. This case also indicated the importance of strong clinical suspicion, as well as aggressive antifungal therapy combined with surgical debridement of affected tissues.

Flemingia macrophylla (Willd.) Prain is an ethnomedicinal plant with high nutritional and medicinal values. In this study, we report the complete chloroplast genome of F. macrophylla. The chloroplast genome has a typical quadripartite structure with a genome size of 152,988 bp, including a large single-copy (LSC) of 83,634 bp, a small single-copy (SSC) of 17,774 bp and two inverted repeats (IRs) of 25,790 bp. The genome contains 129 genes, including 84 protein-coding, 37 tRNA and 8 rRNA genes. The overall GC content is 35.1%. Phylogenetic analysis showed that F. macrophylla grouped with a clade containing the genera of Fagelia, Dolichos, Eriosema, Dunbaria and Cajanus in Fabaceae. This study provides essential data and insight for understanding the phylogenetic placement of Flemingia.

Objective To investigate the role of arachidonic acid (AA) metabolism-related endoplasmic reticulum genes in the development of HCC in a mouse hepatocellular carcinoma (HCC) microenvironment. Methods The function of differentially expressed endoplasmic reticulum membrane genes (ADEGs) involved in AA metabolism was analyzed by RNA-seq and bioinformatics using AA metabolism-related genes as the background, tumor tissues and paracancer tissues of mice were collect as the sample materials, and the expression of ADEGs was verified by RT-qPCR. Results There was a total of 35 ADEGs in HCC (gene expression in per million per thousand transcripts in sequencing base sequencing contained in the base sequence fragment number (FPKM) ≥2 or ≤0.5, and false positive rate (FDR) was ≤0.05), they were involved in the two biological applications (BPs), five cellcomponents (CCs), nine molecular functions(MFs), a protein loci sequence characteristics (US) and six(KPs) signal channel. The function of these genes was mainly focused on the endoplasmic reticulum membrane, especially the effect of iron ion binding(IIB)on the epoxygenase P450 pathway (EPP). Further analysis revealed that ADEGs in IIB had extensive single nucleotide site variation (SNV) and insertion and deletion (INDEL) in the HCC microenvironment, and its occurrence frequency was positively correlated with gene expression (r=0.83). Conclusions ADEGs in HCC microenvironment may cause EPP abnormalities mainly through IIB in the endoplasmic reticulum, thus playing an important role in the development and progression of HCC, SNV and INDEL may be important ways to regulate gene expression.