Although enteric glial cell (EGC) abnormal activation is reported to be involved in the pathogenesis of Parkinson's disease (PD), and inhibition of EGC gliosis alleviated gut and dopaminergic neuronal dysfunction was verified in our previous study, the potential role of gut microbiota on EGC function in PD still need to be addressed. In the present study, fecal microbiota transplantation revealed that EGC function was regulated by gut microbiota. By employing 16S rRNA and metabolomic analysis, we identified that 3-indolepropionic acid (IPA) was the most affected differential microbial metabolite that regulated EGC gliosis. The protective effects of IPA on PD were validated in rotenone-stimulated EGCs and rotenone (30 mg/kg i.g. for 4 weeks)-induced PD mice, as indicated by decreased inflammation, improved intestinal and brain barrier as well as dopaminergic neuronal function. Mechanistic study showed that IPA targeted pregnane X receptor (PXR) in EGCs, and inhibition of IL-13Rα1 involved cytokine-cytokine receptor interaction pathway, leading to inactivation of downstream JAK1-STAT6 pathway. Our data not only provided evidence that EGC gliosis was critical in spreading intestinal damage to brain, but also highlighted the potential role of microbial metabolite IPA in alleviating PD pathological damages through gut-brain axis.

[This corrects the article DOI: 10.1016/j.apsb.2025.02.029.].

Palmitoylation, an essential covalent attachment of a fatty acid (usually C16 palmitate) to cysteine residues within proteins, is crucial for regulating protein functionality and enzymatic activities. This lipid modification facilitates the anchoring of proteins to cellular membranes, dictating their subcellular distribution and influencing protein transport dynamics and intracellular positioning. Additionally, it plays a role in regulating protein degradation through the ubiquitin-proteasome system. Palmitoylation is implicated in the pathogenesis and progression of cardiovascular diseases by modulating substrates and prompting additional post-translational modifications, as well as by interacting with other molecular alterations. Moreover, an intervention strategy focusing on palmitoylation processes is anticipated to offer novel therapeutic avenues for cardiovascular pathologies and address extant challenges in clinical settings. This review consolidates current research on the role and importance of palmitoylation in cardiovascular diseases by exploring its regulatory functions, the catalyzing enzymes, and the involved substrates. It highlights recent discoveries connecting palmitoylation-targeted therapies to cardiovascular health and examines potential approaches and future challenges in cardiovascular treatment.

Objective To use analytic hierarchy process(AHP)-entropy weight method to evaluate the quality of symbiotic Armillaria in Gastrodia elata Bl.Methods The physiological,growth and chemical indexes of 6 strains of G.elata symbiotic Armillaria were used as evaluation factors,and the weight coefficients of each index were calculated by the AHP-entropy weight method.A comprehensive quality evaluation system was established to evaluate the quality of Armillaria strains,and the results were verified by red G.elata and hybrid G.elata combined planting experiments.Results The quality evaluation results showed that extracellular xylanase activity,extracellular cellulase activity and total sugar weight were relatively high,among which strains N6 and N3 ranked the top.The results showed that strains N5 and N4 combined with red G.elata had better quality,that strains N6 and N3 combined with hybrid G.elata had better quality.Conclusion The correlation of extracellular xylanase activity and total sugar of cellulase activity should be paid attention to in the quality evaluation of symbiotic Armillaria in G.elata.The quality evaluation system constructed in this artilcle is basically consistent with the results of hybrid G.elata combined with hybrid G.elata experiment,which can provide references for the quality screening of symbiotic Armillaria in G.elata.

Plant-derived nanovesicles have gained attention given their similarity to mammalian exosomes and advantages such as low cost, sustainability, and tissue targeting. Thus, they hold promise for disease treatment and drug delivery. In this study, we proposed a time-efficient method, PEG 8000 combined with sucrose density gradient centrifugation to prepare ginger-derived nanovesicles (GDNVs). Subsequently, curcumin (CUR) was loaded onto GDNV by ultrasonic incubation. The optimum conditions for ginger-derived nanovesicles loaded with curcumin (CG) were ultrasound time of 3 min, a carrier-to-drug ratio (GDNV:CUR) of 1:1. The study achieved a high loading capacity (94.027% ± 0.094%) and encapsulation efficiency (89.300% ± 0.344%). Finally, the drugs' in vivo distribution and anti-colitis activity were investigated in mice. CG was primarily distributed in the colon after oral administration. Compared to CUR and GDNV, CG was superior in improving disease activity, colon length, liver and spleen coefficients, myeloperoxidase activity, and biochemical factor levels in ulcerative colitis (UC) mice. In addition, CG plays a protective role against UC by modulating serum metabolite levels and gut flora. In summary, our study demonstrated that GDNV can be used for CUR delivery with enhanced therapeutic potential.

BACKGROUND: Current guidelines recommend hepatocellular carcinoma (HCC) screening in high-risk populations. However, the ideal HCC screening interval and screening modality have not been determined. This study aimed to compare the screening efficacy among different modalities with various intervals. METHODS: PubMed and other nine databases were searched through June 30, 2021. Binary outcomes were pooled using risk ratio (RR) with 95% confidence intervals (CIs). Survival rates were also pooled using RR with 95% CIs because most eligible studies only provided the number of survival patients instead of hazard ratio. RESULTS: In all, 13 studies were included. Two random controlled trials (RCTs) and six cohort studies compared screening intervals for ultrasonography (US) screening and found no significant differences between shorter (3- or 4-month) and longer (6- or 12-month) screening intervals in terms of early HCC proportion, HCC significant mortality, 1-year survival rate; screening at 6-month interval significantly increased the proportion of early HCC (RR = 1.17, 95% confidence interval [CI]: 1.08-1.26) and prolonged the 5-year survival rate (RR = 1.39, 95% CI: 1.07-1.82) relative to the 12-month interval results. Three other RCTs and two cohort studies compared different screening modalities in cirrhosis or chronic hepatitis B, which indicated no statistical differences in the proportion of early HCC (RR = 0.89, 95% CI: 0.40-1.96) and HCC mortality (RR = 0.69, 95% CI: 0.23-2.09) between the biannual US and annual computed tomography (CT screening). Biannual US screening showed a lower proportion of early HCC than biannual magnetic resonance imaging (MRI) (RR = 0.60, 95% CI: 0.37-0.97) and biannual US combined with annual CT (RR = 1.31, 95% CI: 1.13-1.51) screening. The proportion of early HCC in the contrast-enhanced US group was slightly higher than that in the B-mode US (RR = 1.08, 95% CI: 1.00-1.23) group. CONCLUSIONS: The evidence suggests that 6 months may be the best HCC screening interval for US screening. The effectiveness of CT and MRI is better than US during same screening intervals. However, MRI and CT are more expensive than US, and CT also can increase the risk of radiation exposure. The selection of CT or MRI instead of US should be carefully considered. REGISTRATION No. CRD42020148258 at PROSPERO website ( https://www.crd.york.ac.uk/PROSPERO/ ).
Humans ; Carcinoma, Hepatocellular/pathology* ; Liver Neoplasms/pathology* ; Liver Cirrhosis/complications* ; Risk Factors ; Cohort Studies

OX40 is a costimulatory receptor that is expressed primarily on activated CD4⁺, CD8⁺, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.
Mice ; Animals ; Receptors, Tumor Necrosis Factor/physiology* ; Receptors, OX40 ; Membrane Glycoproteins ; Ligands ; Antibodies, Monoclonal/pharmacology* ; Antineoplastic Agents/pharmacology*

The purpose of this article is to review the research progress on fear of dementia， and to provide references for clinical treatment and nursing care. Fear of dementia is a widespread problem for adults， and adults with high degrees of fear were more likely to develop adverse psychological consequences， including aggravation of anxiety and depression， decreased inclination toward health-promoting behaviours， avoidance of medical treatment， and suicidal ideation. At present， domestic and foreign studies have mainly focused on the current situation and influencing factors of fear of dementia. Therefore， this article gives a review on the fear of dementia in terms of its concept， incidence， impact， influencing factors， assessment tools and intervention measures， with a view to provide a reference for the subsequent studies.

Objective: To assess left atrial(LA)function by evaluating changes of LA wall movement and volume detected by real-time three-dimensional speckle tracking imaging(RT3D-STI)in elderly patients with ischemic mitral regurgitation(IMR). Methods: Eighty-six elderly patients with coronary heart disease(CHD)were enrolled in this study.According to whether or not to have IMR, the patients were divided into the pure CHD group(n=32)and the CHD-induced ischemic mitral regurgitation(IMR)group(n=54, including 20 cases of mild IMR, 18 cases of moderate IMR and 16 cases of severe IMR). Thirty-two healthy elderly volunteers were considered as control group.RT3D-STI was used to evaluate the global atrial longitudinal strain(GLS), global circumferential strain(GCS), global radial strain(GRS)and LA maximal, minimal and pre-systolic volumes(LAVmax, LAVmin, and LAVp). LA ejection fraction(LAEF), LA passive ejection fraction(LApEF)and LA active ejection fraction(LAaEF)were calculated.The relationship of LA volume changes and myocardial strain with LA function was analyzed. Results: The left ventricular ejection fraction(LVEF)and LAEF were reduced in CHD group and IMR group as compared with the control group, and were lower in IMR group than in CHD group(P<0.05). Compared with the control group, the LAVmin was increased, and the LAaEF was decreased in the IMR group(P<0.05). Compared with the control group, the GLS, GCS, GRS were declined in the CHD and IMR groups, and were lower in IMR group than in control group(P<0.05). Along with the increased severity of regurgitation, GLS, GCS, and GRS were decreased in varying degrees.The standard deviations of time to peak longitudinal strains(TLS-SD), of time to peak circumferential strains(TCS-SD), and of time to peak radial strain(TRS-SD)rose in the IMR group as compared with the control group(P<0.05). The myocardial motion indicators(GLS, GCS, GRS)had a quite strong correlation with LAEF in the CHD and IMR groups(CHD group: r=-0.745, -0.718 and 0.627, P=0.006, 0.007 and 0.009; IMR group: r=-0.785, -0.781, 0.643, P=0.006, 0.007 and 0.008). The receiver operating characteristic(ROC)curves analysis showed that the sensitivity and specificity of TLS-SD, TCS-SD and TRS-SD were 89.7% and 81.8%, 78.6% and 84.8%, 85.7% and 72.1%, respectively in the evaluation of LA function changes. Conclusions RT3D-STI can precisely and objectively assess the LA function changes by measuring the volume changes and tracing the myocardial motion in elderly IMR patients.

Objective:To create AAPM TG 119 test plans for intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) in order to evaluate the accuracy of the United Imaging Healthcare′s URT treatment planning system (URT-TPS). The plans were delivered to the phantom using the United Imaging Healthcare′s URT-Linac 506C.Methods:The overall accuracy of IMRT and VMAT planning, measurement, and analysis were evaluated for four test geometries provided by American Association of Physicists in Medicine (AAPM) Task Group Report 119(TG-119) on multi-target, prostate, head and neck and C-shape (easy). The dose distributions were measured in the coronal plane. The point measurements were measured by a Farmer type ion chamber and fluence measurements were completed with film and Delta4 phantom, respectively. Measured planar dose distributions were analyzed using gamma index with criteria 3%/3 mm.Results:For IMRT and VMAT plans, the planning results matched the TG-119 planning results. Measured point doses of IMRT and VMAT were within 2.62% and 3.90% of the planned doses, respectively. Measured film dosimetry gamma values of IMRT and VMAT were> 97.50% and> 93.27%, respectively.Conclusion:Based on these analyses which were performed in line with the TG119 recommendations, it is evident that the URT treatment planning system and URT-Linac 506C have commissioned IMRT and VMAT techniques with adequate accuracy.