The roots of Kadsura coccinea is commonly used in Tujia ethnomedicine, named „heilaohu“, having the effect of treating rheumatic arthritis (RA). Chemical investigation on the ethanol extract of heilaohu led to the isolation of one undescribed cuparane sesquiterpenoid, heilaohusesquiterpenoid A, one undescribed carotane sesquiterpenoids, heilaohusesquiterpenoid B, and eighteen sesquiterpene derivatives. Their structures were subsequently determined based on their 1D and 2D-NMR, HR-ESI-MS, and ECD spectroscopic data. Gaultheriadiolide was the most cytotoxic compound against the proliferation of rheumatoid arthritis-fibroblastoid synovial (RA-FLS) cells with an IC50 value of 9.37 μM. In the same line, nine compounds exhibited significant inhibition effects against TNF-α and IL-6 release in the LPS-induced RAW264.7 cells with IC50 values ranging between 1.03 and 10.99 μM. The potential molecular mechanisms of the active compounds against RA were established through pharmacological network analysis based on the initial screening results. Experimental validation showed that gaultheriadiolide suppressed inflammation by inhibiting the NF-kB and JAK2/STAT3 pathways. This study enriches the structural diversity of sesquiterpenes in K. coccinea and lays a foundation for further anti-RA and anti-inflammatory studies.Licorice is a medicinal and food plant widely used to treat diseases and produce food additives, because of its unique chemical constituents like polysaccharides, flavones, and saponins. Glycyrrhiza Polysaccharides (GPS-1) are water-soluble neutral polysaccharides extracted from licorice. Currently, GPS-1 is administrated to chickens by gavage every d for 14 d to observe the impact of GPS-1 on the Newcastle disease vaccine. To determine the immunity of these chickens to NDV, blood serum levels of hemagglutinin-inhibition (HI) antibody, and immunoglobulins IgA and IgG were measured. Meanwhile, the expression levels of cytokines IL-2, IL-4, IL-17, and IFN-γ were measured to evaluate the degree of immune booster activity. The chickens‘ spleen and peripheral blood lymphocytes displayed a significant increase in the proportion of CD4+ and CD8+ T cells after booster treatments with GPS-1. The results indicated that GPS-1 had a significant, dose-dependent, immune-boosting effect which could enhance NDV vaccine immunity in chickens.

Exosomal miRNAs have attracted increasing interest as potential biomarkers and treatment targets for cancers, however, glioblastoma (GBM)-related exosomal miRNAs remain rarely reported. The study aimed to screen crucial serum exosomal miRNAs in GBM patients and explored their possible mechanisms.

Serum exosomal miRNA profile datasets of GBM patients and normal controls were downloaded from the Gene Expression Omnibus database (GSE112462 and GSE122488). The differentially expressed miRNAs (DEMs) were identified using the limma method. Their diagnostic values were assessed by receiver operating characteristic (ROC) curve analysis. The target genes of DEMs were predicted by the miRwalk 2.0 database. Function enrichment analysis was performed using the DAVID database. The expression and prognosis of target genes were validated using TCGA sequencing data and immunohistochemistry.

Seven DEMs were shared in two datasets, among which hsa-miR-183-5p and hsa-miR-98-5p as well as has-miR-323-3p or has-miR-19b-3p costic biomarkers and therapeutic targets for GBM.

These findings suggest these four exosomal miRNAs may represent potential diagnostic biomarkers and therapeutic targets for GBM.

Post-stroke depression (PSD) is a common psychiatric complication of stroke and is associated with the subsequent prognosis, yet still lacking of enough attention. PSD is preventable, and psychotherapy is an alternative prophylactic treatment which needs more solid evidences to confirm its efficacy. In this study, group Acceptance and Commitment Therapy (G-ACT) was performed in acute stroke patients to see if it can effectively relieve depressive symptoms and improve neurological function. The efficacy was also evaluated in stroke patients of different severity.

One hundred and four hospitalized patients with acute ischemic stroke were enrolled according to the inclusioncriteria and exclusion criteria. After baseline evaluation, they were randomly allocated to the intervention (G-ACT) group and the control (usual care) group. Patients in the control group received routine stroke treatment, while those in the intervention group were given additional G-ACT treatment (5 sessions, 45-55 min/session). Both of hs follow-up (p = 0.004; p = 0.033).

G-ACT seems to be a viable and effective treatment for preventing PSD in the acute phase of stroke, while the efficacy of which on improving neurological deficits needs to be further evaluated.

G-ACT seems to be a viable and effective treatment for preventing PSD in the acute phase of stroke, while the efficacy of which on improving neurological deficits needs to be further evaluated.

To assess the potential effect of dl-3-N-butylphthalide (dl-NBP) for the proliferation and differentiation of neural stem cells (NSCs) against hypoxia and the underlying mechanism.

Hippocampal NSCs were obtained from fetal rats. NSCs combined with dl-NBP and single NSCs were cultured. The impact of siRNA-mediated hypoxia-inducible factor-1alpha (HIF-1α) knockdown on NSCs was detected with western blotting (WB) and quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR). Cell-counting kit-8 assay was used for evaluating the viability of NSCs. Levels of HIF-1α protein were measured using WB, and vascular endothelial growth factor (VEGF) expression was quantified using RT-qPCR and enzyme-linked immunosorbent assay.

Compared with 7 different concentrations of dl-NBP, 0.25g/L was determined as the optimal concentration to significantly increase the viability of NSCs (p < 0.001). Dl-NBP can significantly increase the viability of hypoxic NSCs (p<0.001) and improve the differentiation of hypoxic NSCs into astrocytes (p=0.001) and oligodendrocytes (p<0.001). Meanwhile, Dl-NBP can significantly elevate levels of HIF-1α protein (p<0.001) and VEGF mRNA (p=0.001) / protein (p<0.001) in NSCs in the hypoxic environment. Vemurafenib However, after transfection with HIF-1α siRNA in NSCs, the viability and differentiation of NSCs was not recovered using dl-NBP under the hypoxic condition, as well as levels of HIF-1α and VEGF.

Dl-NBP can reverse the weaker proliferation and differentiation power of NSCs in the hypoxic environment. The HIF-1α – VEGF pathway may be implicated in this protective effect of dl-NBP.

Dl-NBP can reverse the weaker proliferation and differentiation power of NSCs in the hypoxic environment. The HIF-1α – VEGF pathway may be implicated in this protective effect of dl-NBP.

Aluminium neurotoxicity has been widely confirmed and mainly manifests as cognitive impairment. Al

can inhibit the expression of ADAM10, a key enzyme of the nonamyloid pathway, but its mechanism of toxicity has not been fully elucidated. Studies have shown that RARs can regulate ADAM10 expression.

We explored whether Al

affects the expression of ADAM10 through RARs, thereby affecting the nonamyloid pathway.

Al

reduced the expressions of RARα, RARβ and ADAM10. The expression levels of the RARα, RARβ and ADAM10 proteins were upregulated in the RA group compared with the control group. In the RA + 200 μmol Al(mal)

group, the downregulation of RARα, RARβ and ADAM10 was weaker than that of the 200 μmol Al(mal)

group, which indicated that RA participated in and upregulated the expression of ADAM10 through RARα and RARβ.

Al

inhibits ADAM10 expression through RARα and RARβ and results in a decrease in the nonamyloid pathway.

Al3+ inhibits ADAM10 expression through RARα and RARβ and results in a decrease in the nonamyloid pathway.

Increasing numbers of autistic children are being educated in mainstream schools. The success of inclusive education is dependent upon multiple factors, including key stakeholders (i.e., teachers and parents). Research has tended to focus on teachers‘ experiences of inclusion with limited focus on parents.

The study aimed to qualitatively investigate parental attitudes and experiences of inclusive education. As such, the research question was What are attitudes towards, and experiences of, inclusive education for parents of autistic children?

Semi-structured interviews were conducted with 12 parents of autistic children. Data was analysed using Thematic Analysis (Braun & Clarke, 2006).

four themes were identified; 1) Feeling Unheard; 2) Implementation of Inclusive Strategies; 3) Social Exclusion; 4) Mental Health and Wellbeing Impact. Findings suggested that parents felt their child struggled socially in mainstream school, with such experiences negatively impacting upon their child’s wellbeing. The detrimental impacts were a result of parents believing school staff dismissed their concerns and thus appropriate strategies for their child were not always implemented.

This highlights the need for school staff and parents to work together to enhance inclusivity both academically and socially for autistic children.

This highlights the need for school staff and parents to work together to enhance inclusivity both academically and socially for autistic children.

No cut-points have been developed for youth with Down syndrome; there is concern that altered gait patterns, decreased energy expenditure and exercise capacity of individuals with Down syndrome may produce inaccurate physical activity data if accelerometer data are analyzed using cut-points from populations with typical development and other IDD diagnoses.

To compare physical activity and sedentary time across existing accelerometer cut-point methods in adolescents with Down syndrome.

In this cross-sectional analysis, participants diagnosed with Down syndrome (n = 37; 15.5 ± 1.9 years; 57 % female) wore an accelerometer on their non-dominant hip for seven-days. Data were analyzed and compared across four physical activity intensity cut-points Evenson, Freedson 4-MET, McGarty, and Romanizi.

Differences in time spent in each intensity across cut-point methods were evident for sedentary (448-615 min/day), light (72-303 min/day) and moderate-to-vigorous (12-77 min/day) activities. Between 0.0-67.6 % of thasurement methods derived from populations with typical development. This is the first manuscript to examine this issue in a sample comprised solely of youth with Down syndrome. Results demonstrate the large variation in time spent in each activity intensity that arise due to the application of different cut-point methods.Varicocele is a condition in which the pampiniform venous plexus in the scrotum dilates abnormally during puberty, affecting testicular growth and semen parameters, and is thought to be a major cause of male infertility. The findings of researches on the presence of the Fas system in sperm are controversial. As the main triggers of apoptosis in the semen of patients with varicocele, in this study, we examined the expression of Fas/Fas-L on sperm cells and also the levels of their soluble forms in seminal plasma. Semen samples were taken from 45 patients with varicocele (study group) and 45 healthy subjects without varicocele (control group) after 3-5 days of ejaculatory abstinence. Flow cytometry was used to examine the expression of Fas and Fas ligand (Fas-L) on Sperm cells. Furthermore, soluble Fas (sFas) and soluble Fas-Ligand (sFas-L) levels in the seminal fluid were determined using an ELISA (enzyme-linked immunosorbent assay). The presence of Fas and Fas-L proteins on the sperm ejaculation surface was not found in the patients with varicocele or the control groups.