Objective: To analyze the relationship between 24 h movement behaviors and cognitive function in children and adolescents, as well as the isotemporal substitution benefits, in order to provide a basis for developing cognitive development intervention strategies among children and adolescents. Methods: Relevant studies were searched in the Web of Science, PubMed, Embase, EBSCO, and China National Knowledge Infrastructure databases from their inception to November 30, 2024. Systematic evaluation was performed after document screening, data extraction and quality assessment. Results: A total of 24 highquality studies were included, comprising 35 295 children and adolescents aged 3-18 years. Adhering to the 24 h activity guidelines was associated with better cognitive performance (19 studies). Additionally, substituting 5-30 minutes per day of moderate to vigorous physical activity (MVPA) or sleep (SLP) for sedentary behavior (SB) or light physical activity (LPA) were associated with improvements in cognitive function (7 studies). There were inconsistencies in the effects of different types of SB (learning or entertainment) on cognitive function. Conclusions Adherence to the 24 h activity guidelines supports cognitive development in children and adolescents, with MVPA and SLP as key intervention targets. Increasing the proportion of MVPA, ensuring adequate SLP, and limiting recreational SB and screen time might be helpful to enhance the combined benefits of these three behaviors.

Eight butyl-phthalides, senkyunolide K(1), senkyunolide N(2), butylphthalide(3), senkyunolide I(4), senkyunolide H(5),(Z)-butylidenephthalide(6),(Z)-ligustilide(7), and 3-butylidene-7-hydroxyphthalide(8) were isolated from the aerial part of Ligusticum sinense by column chromatography on silica gel column, ODS, Sephadex LH-20 and semi-preparative HPLC. Their structures were elucidated on the basis of spectroscopic and chemical data, especially NMR and MS. Compound 1 was a new butyl-phthalide and compounds 2-8 were isolated from the aerial part of L. sinense for the first time. Furthermore, the inhibitory activities of compounds 1-8 against the nitric oxide(NO) production induced by lipopolysaccharide(LPS) in mouse RAW264.7 macrophages in vitro were evaluated. The results showed that compounds 1-8 exerted inhibitory activities on NO production with IC_(50) of 19.34-42.16 μmol·L~(-1).
Animals ; Mice ; Nitric Oxide/biosynthesis* ; Ligusticum/chemistry* ; Benzofurans/isolation & purification* ; Drugs, Chinese Herbal/isolation & purification* ; Macrophages/immunology* ; RAW 264.7 Cells ; Molecular Structure

The study investigated the specific mechanism by which oxocrebanine, the anti-hepatic cancer active ingredient in Stephania hainanensis, inhibits the proliferation of hepatic cancer cells. Firstly, methyl thiazolyl tetrazolium(MTT) assay, 5-bromodeoxyuridine(BrdU) labeling, and colony formation assay were employed to investigate whether oxocrebanine inhibited the proliferation of HepG2 and Hep3B2.1-7 cells. Propidium iodide(PI) staining was used to observe the oxocrebanine-induced apoptosis of HepG2 and Hep3B2.1-7 cells. Western blot was employed to verify whether apoptotic effector proteins, such as cleaved cysteinyl aspartate-specific protease 3(c-caspase-3), poly(ADP-ribose) polymerase 1(PARP1), B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), Bcl-2 homologous killer(Bak), and myeloid cell leukemia-1(Mcl-1) were involved in apoptosis. Secondly, HepG2 cells were simultaneously treated with oxocrebanine and the autophagy inhibitor 3-methyladenine(3-MA), and the changes in the autophagy marker LC3 and autophagy-related proteins [eukaryotic translation initiation factor 4E-binding protein 1(4EBP1), phosphorylated 4EBP1(p-4EBP1), 70-kDa ribosomal protein S6 kinase(P70S6K), and phosphorylated P70S6K(p-P70S6K)] were determined. The results of MTT assay, BrdU labeling, and colony formation assay showed that oxocrebanine inhibited the proliferation of HepG2 and Hep3B2.1-7 cells in a dose-dependent manner. The results of flow cytometry suggested that the apoptosis rate of HepG2 and Hep3B2.1-7 cells increased after treatment with oxocrebanine. Western blot results showed that the protein levels of c-caspase-3, Bax, and Bak were up-regulated and those of PARP1, Bcl-2, and Mcl-1 were down-regulated in the HepG2 cells treated with oxocrebanine. The results indicated that oxocrebanine induced apoptosis, thereby inhibiting the proliferation of hepatic cancer cells. The inhibition of HepG2 cell proliferation by oxocrebanine may be related to the induction of protective autophagy in hepatocellular carcinoma cells. Oxocrebanine still promoted the conversion of LC3-Ⅰ to LC3-Ⅱ, reduced the phosphorylation levels of 4EBP1 and P70S6K, which can be reversed by the autophagy inhibitor 3-MA. It is prompted that oxocrebanine can inhibit the proliferation of hepatic cancer cells by inducing autophagy. In conclusion, oxocrebanine inhibits the proliferation of hepatic cancer cells by inducing apoptosis and autophagy.
Humans ; Apoptosis/drug effects* ; Autophagy/drug effects* ; Cell Proliferation/drug effects* ; Hep G2 Cells ; Liver Neoplasms/genetics* ; Carcinoma, Hepatocellular/genetics* ; Caspase 3/genetics*

Intervention in chronically activated microglia-mediated neuroinflammation is a novel approach to treat Alzheimer's disease (AD). The low permeability of the blood‒brain barrier (BBB) and non-selective distribution in the brain severely restrict AD drugs' disease-modifying efficacy. Here, an immunosuppressant TREM2-lowing antisense oligonucleotides (ASOs) and resveratrol co-loaded cationic liposome is developed as an immune reprogramming nanomodulator modified by acid-cleavable BBB-targeting peptide and microglia-targeting peptide (Res@TcMNP/ASO) for AD management. Res@TcMNP/ASO can enter brain endothelial cells via D-T7 peptides. Then D-T7 undergoes an acid-responsive cleavage, facilitating the escape of Res@MNP/ASO from endo/lysosomes to cross the BBB. The detached Res@MNP/ASO specifically targets M1-phenotype microglia via exposed MG1 peptides to prompt the simultaneous delivery of two drugs into activated microglia. This nanomodulator can not only restore the immune function of microglia through TREM2-lowing ASO but also mitigate the immune stimulation to microglia caused by reactive oxygen species (ROS) through resveratrol, thereby synergistically inhibiting the chronic activation of microglia to alleviate neuroinflammation in AD. Our results indicate that this combination treatment can achieve significant behavioral and cognitive improvements in late APP/PS1 mice.

OBJECTIVES: To investigate the effect of Haematococcus pluvialis (HP) on bleomycin (BLM)-induced pulmonary fibrosis in mice and on TGF-β1-induced human fetal lung fibroblasts (HFL1). METHODS: Thirty male C57BL/6 mice were randomly divided into control group, BLM-induced pulmonary fibrosis model group, low- and high-dose HP treatment groups (3 and 21 mg/kg, respectively), and 300 mg/kg pirfenidone (positive control) group. The effects of drug treatment for 21 days were assessed by examining respiratory function, lung histopathology, and expression of fibrosis markers in the lung tissues of the mouse models. In TGF-β1-induced HFL1 cell cultures, the effects of treatment with 120, 180 and 240 μg/mL HP or 1.85 μg/mL pirfenidone for 48 h on expression levels of fibrosis markers were evaluated. Transcriptome analysis was carried out using the control cells and cells treated with TGF-β1 and 240 μg/mL HP. RESULTS: HP obviously alleviated BLM-induced lung function damage and fibrotic changes in mice, evidenced by improved respiratory function, lung tissue morphology and structure, inflammatory infiltration, and collagen deposition and reduced expressions of fibrotic proteins. HP at the high dose produced similar effect to PFD. In TGF-β1-induced HFL1 cells, treatment with 240 μg/mL HP significantly reduced the mRNA and protein expression levels of α-SMA and FN. Transcriptome analysis revealed that multiple key genes and pathways mediated the protective effect of HP against pulmonary fibrosis. CONCLUSIONS HP alleviates pulmonary fibrosis in both the mouse model and cell model, possibly as the result of the synergistic effects of its multiple active components.
Animals ; Pulmonary Fibrosis/chemically induced* ; Bleomycin/adverse effects* ; Mice, Inbred C57BL ; Male ; Mice ; Fibroblasts/drug effects* ; Lung/pathology* ; Transforming Growth Factor beta1/pharmacology* ; Myofibroblasts/drug effects* ; Humans ; Pyridones

Objective To analyse the analgesic effect and possible mechanism of panax notoginseng saponin (PNS) on mouse models of chronic inflammatory pain caused by complete Freund’s adjuvant (CFA). Methods A total of 48 male C57BL/ 6J mice were divided randomly into four groups: normal saline control group (Ctrl), CFA group (CFA), CFA + PNS group (CFA+PNS), CFA + dexamethasone (DEX) group (CFA+DEX). Von Frey filaments were used to detect mechanical pain in mice. Immunohistochemistry was used to detect the number and morphological changes of glial fibrillary acidic protein (GFAP) positive astrocytes. Western blotting was used to detect the expressions of GFAP, nucleotide-binding and oligomerization domain(NOD)-like receptor thermal protein domain associated protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), Caspase-1, interleukin (IL)-1β, and IL-18 in mice’s spinal cord segments in each group. Results Compared with the Ctrl group, mice in the CFA group showed a significant decrease in mechanical pain thresholds at day 1, day 3, day 5, day 7, and day 14. Additionally, there was a significant decrease in NLRP3, ASC, Caspase-1, IL-1β and IL-18 in the spinal cord of the mice. PNS intervention could relieve mechanical pain and down-regulate the expressions of NLRP3, ASC, Caspase-1, IL-1β and IL-18 in the spinal cord of mice, with no significant difference compared with the CFA+DEX group. CFA group mice had significantly more GFAP positive cells in their posterior horns than Ctrl group mice, as measured by immunohistochemistry; PNS intervention decreased the number of GFAP positive cells in the posterior horn of the spinal cord in model mice;DEX had no effect on the number of GFAP positive cells in the dorsal horn of spinal cord. According to Western blotting results, GFAP expression in the spinal cord of the CFA group was significantly more than that of the Ctrl group; PNS intervention significantly reduced GFAP expression in the spinal cord of CFA group mice;DEX had no effect on the expression of GFAP in the posterior horn of spinal cord. Conclusion PNS has a good alleviating effect on inflammatory pain, and its mechanism may be related to inhibition of astrocyte activation and NLRP3 inflammasome activation.

Objective To explore the effects of multi-component exercise intervention (MET) based on different rates of resistance training on physical function and depression status in elderly patients with frailty. Methods Eighty hospitalized elderly patients with frailty in the Geriatric Department were randomly divided into control group (n=40) and study group (n=40). The elderly patients with frailty in the control group received routine medical intervention, while those in the study group received MET on the basis of the control group. According to the principle of random allocation, the study group was further divided into high-resistance group (n=20) and low-resistance group (n=20). The high-resistance group performed three sets of resistance training at 75% of the one-repetition maximum (1RM) intensity, while the low-resistance group performed three sets of resistance training at 45%, 60% and 75% of the 1RM intensity. The changes in 1RM of shoulder, hip, and knee flexion and extension activities were compared among the three groups before and after the intervention; the scores of the Short-form Physical Performance Battery (SPPB), the Hamilton Depression Rating Scale (HAMD), and the Short-form Quality of Life with 12 items (SF-12) were also compared among the three groups before and after the intervention. Results After the intervention, the 1RM of joint activities in the high-resistance group was significantly higher than that in the low-resistance group and the control group, and the 1RM of joint activities in the low-resistance group was also significantly higher than that in the control group (P < 0.05). After the intervention, the SPPB score in the high-resistance group was significantly higher than that in the low-resistance group and the control group, and the SPPB score in the low-resistance group was also significantly higher than that in the control group (P < 0.05); the HAMD score in the high-resistance group was significantly lower than that in the low-resistance group and the control group, and the HAMD score in the low-resistance group was also significantly lower than that in the control group (P < 0.05). After the intervention, the total Physical Component Summary (PCS) and Mental Component Summary (MCS) scores in the high-resistance group were significantly higher than those in the low-resistance group and the control group, and the PCS and MCS scores in the low-resistance group were also significantly higher than those in the control group (P < 0.05). Conclusion MET can improve physical function and depression status in elderly patients with frailty, and appropriate increase of the resistance training rate can further enhance the positive effects of MET.

Following concerted efforts for over 7 decades, great achievements have been gained in the national schistosomiasis control program of China. Currently, China is moving towards the stage of schistosomiasis elimination, when the major task is to make full use of available resources to improve schistosomiasis surveillance and response to sustainably consolidate gained schistosomiasis control achievements and prevent re-emerging schistosomiasis. There is therefore an urgent need for optimization of interventions for schistosomiasis elimination. Based on analysis of socioeconomic features at different stages of the national schistosomiasis control program in China, this review discusses the relationship between the needs of assessment of schistosomiasis elimination interventions and the optimized strategy of schistosomiasis elimination at different stages of the national schistosomiasis control program using a marginal benefit approach and proposes the optimized schistosomiasis elimination strategy that allows the highest marginal benefit with currently available schistosomiasis elimination costs, so as to provide the optimal strategic pathway to schistosomiasis elimination and facilitate the achievement of the targets set in Healthy China 2030.

Objective : To explore the regulatory effects of ResolvinD1 (RVD1) on autophagy and apoptosis of cardiomyocytes in aging rats , and the effects of RVD1 on mitochondria⁃associated endoplasmic reticulum membranes (MAMs) of myocardial tissue . Methods : Thirty 18⁃month⁃old SD rats were randomly divided into model group , low⁃dose RVD1 group and high⁃dose RVD1 group , with 10 rats in each group , and another 10 6 ⁃month⁃old SD rats were selected as control group . The low⁃dose RVD1 group and high⁃dose RVD1 group were injected with 50 ng/ml and 100 ng/ml RVD1 through the tail vein , respectively , control group and model group were injected with the same amount of phosphate buffered saline (PBS) for 21 days . The β ⁃galactosidase activity of rat myocardial tissue was determined by p ⁃nitrophenol method , the histopathological changes of rat myocardial tissue were detected by hematoxylin⁃eosin (HE) staining , and the collagen deposition in rat myocardial tissue was observed by Masson staining , apoptosis of rat myocardial cells was detected by dUTP in situ end labeling mediated by terminal deoxynucleotide transferase(TUNEL) , the expression of autophagy marker microtubule⁃associated protein 3 (LC3) was detecotide transferase(TUNEL) , the expression of autophagy marker microtubule⁃associated protein 3 (LC3) was detected by immunohistochemical S ⁃P method , the ratio of LC3 ⁃ Ⅱ/LC3 ⁃ Ⅰ and the expression of Beclin⁃1 , p62 in rat myocardial tissue were determined by Western blot , the structure of MAMs in rat myocardial tissue was observed by transmission electron microscopy , the expression levels of glucose⁃regulatory protein 75 (GRP75) , volt⁃dependent anion channel 1 (VDAC1) and mitochondrial fusion protein 2 (Mfn2) in rat myocardial tissue were determined by Western blot . Results : Compared with model group , β ⁃galactosidase activity of myocardial tissue decreased in low⁃dose RVD1 group and high⁃dose RVD1 group (P < 0. 05) , myocardial fiber breakage and myocardial cell damag were significantly alleviated , collagen fiber deposition was significantly reduced , and the proportion of TUNEL positive cells in myocardial tissue decreased (P < 0. 05) , the positive rate of LC3 protein increased (P < 0. 05) , the ratio of LC3 ⁃ Ⅱ/LC3 ⁃ Ⅰ increased , the relative expression level of Beclin⁃1 protein was up⁃regulated and the relative expression level of p62 protein was down⁃regulated ( P < 0. 05) , the structure of MAMs was tighter , and the percentage of MAMs in mitochondrial circumference also increased (P < 0. 05) , the relative protein expressions of GRP75 , VDAC1 and Mfn2 were up⁃regulated (P < 0. 05) . Compared with low⁃dose RVD1 group , β ⁃galactosidase activity in high⁃dose RVD1 group further decreased ( P < 0. 05) , no obvious damage was observed in myocardial tissue , collagen fiber deposition was further decreased , the proportion of TUNEL positive cells in myocardial tissue decreased (P < 0. 05 ) , and the positive rate of LC3 protein increased ( P < 0. 05 ) , LC3 ⁃ Ⅱ/LC3 ⁃ Ⅰ ratio increased , Beclin⁃1 relative expression level was up⁃regulated and p62 relative expression level was down⁃regulated (P < 0. 05) , the structure of MAMs was more compact , and their percentage in mitochondrial circumference further increased (P < 0. 05 ) , the relative expressions of GRP75 , VDAC1 and Mfn2 were further up⁃regulated ( P <0. 05) . Conclusion RVD1 can activate autophagy , alleviate myocardial apoptosis and collagen fiber deposition, and promote mitochondria⁃associated endoplasmic reticulum membranes in aging rats .