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Cognitive decline and memory impairment are subsequently result in neuronal apoptosis and synaptic damage. Aberrant regulation of microRNAs has been implicated in the pathogenesis of Alzheimer's disease (AD) and may play a pivotal role in the early stages of the disease. In this study, we identified the critical role of miR-4763-3p in AD pathogenesis, focusing on early-stage mild cognitive impairment (AD-MCI). Leveraging fluorescence in situ hybridization, we observed miR-4763-3p upregulation in AD hippocampal tissue, colocalizing with Aβ and Tau. Antagomir-mediated inhibition of miR-4763-3p ameliorated cognitive decline in AD-MCI mice. RNA-seq and functional assays revealed that miR-4763-3p targets ATP11A, and antagomir enhancing inward flipping of the "eat me" phosphatidylserine signal on the surface of neuronal cells, autophagy, and clearance of Aβ/lipofuscin, while reducing neuroinflammation and neuronal apoptosis. Mechanistically, miR-4763-3p modulates the PI3K/AKT/mTOR/Bcl2 pathway, thereby promoting neuronal autophagy and reducing apoptotic crosstalk. These findings underscore miR-4763-3p as a therapeutic target for AD-MCI, offering a novel strategy to enhance neuronal autophagy, alleviate inflammation, and improve cognitive function., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The delay in wound healing caused by chronic wounds or pathological scars is a pressing issue in clinical practice, imposing significant economic and psychological burdens on patients. In particular, with the aging of the population and the increasing incidence of diseases such as diabetes, impaired wound healing is one of the growing health problems. MicroRNA (miRNA) plays a crucial role in wound healing and regulates various biological processes. Our results show that miR-618 was significantly upregulated during the inflammatory phase of wound healing.Subsequently, miR-618 promotes the secretion of pro-inflammatory cytokines and regulates the proliferation and migration of keratinocytes. Mechanistically, miR-618 binds to the target gene- Atp11b and inhibits the PI3K-Akt signaling pathway, inhibiting the epithelial-mesenchymal transition (EMT) of keratinocytes. In addition, the PI3K-Akt signaling pathway induces the enrichment of nuclear miR-618, and miR-618 binds to the promoter of Lin7a to regulate gene transcription. Intradermal injection of miR-618 antagomir around full-thickness wounds in peridermal mice effectively accelerates wound closure compared to control. In conclusion, miR-618 antagomir can be a potential therapeutic agent for wound healing.

Light, as a critical environmental factor, plays a pivotal role in photosynthesis, ultimately influencing the timing of bud flush in tea plants. However, the synergistic effects of different photoperiods and light qualities on the timing of bud flush in the albino tea cultivar 'HuangKui' (later germination variety) remain unknown. Thus, the objective of this study was to investigate the effects of different photoperiods (12L/12D, 14L/10D, 16L/8D, and 18L/6D, where L = the number of daylight hours and D = the number of hours of darkness) and ratios of red (R) to blue (B) light (R/B 1:1, R/B 1:2, R/B 1:3, and R/B 2:1) on the germination and growth of the albino tea variety 'HuangKui'. In our study, we examined how different photoperiods and red light and blue light affected tea germination and growth by investigating the timing of bud flush, photosynthesis, chlorophyll content, and growth indicators. First, our study showed that 'HuangKui' germinated 4 days, 2 days, and 1 day earlier under the 16L/8D photoperiod at the one bud and one leaf period compared with plants cultivated under the 12L/12D, 14L/10D, and 18L/6D photoperiods under light simulating the solar spectrum. Also, the growth of 'HuangKui' was maximumly promoted under the 16L/8D photoperiod treatment. Additionally, the earliest germination of 'HuangKui' was observed for the 16L/8D photoperiod under the R/B 2:1 (red/blue) treatment compared with the other treatments. Moreover, the greatest plant height, length of the new shoots, and new leaf areas were detected in the albino tea variety 'HuangKui' under R/B 2:1. Moreover, the contents of auxin (indole acetic acid, IAA) and trans-zeatin (tZ) under R/B 2:1 were significantly higher than those under the R/B 1:1 and control treatments with the 16L/8D photoperiod. Additionally, the auxin-related expression levels of CsIAA13 , CsGH3.1 , CsAUX1 , and CsARF2 under the R/B 2:1 treatment were significantly higher than those in the control. The expression of CsARR-B , a positive regulator of cytokinin-related genes, was significantly higher under the R/B 2:1 treatment than under the control treatment, while the opposite result was found for the expression of the negative regulator CsARR-A . Therefore, the R/B 2:1 treatment with the 16L/8D photoperiod was an appropriate means of timing the bud flush for the albino tea variety 'HuangKui', which may be related to IAA or tZ signal transduction. In conclusion, our research offers a novel lighting strategy that promotes the germination and growth of albino tea cultivars.

Rheumatoid arthritis (RA) is an autoimmune disease that affects the living quality of patients, especially the elderly population. RA-related morbidity and mortality increase significantly with age, while current clinical drugs for RA are far from satisfactory and may have serious side effects. Therefore, the development of new drugs with higher biosafety and efficacy is demanding. Black phosphorus nanosheets (BPNSs) have been widely studied because of their excellent biocompatibility. Here, we focus on the inherent bioactivity of BPNSs, report the potential of BPNSs as a therapeutic drug for RA and elucidate the underlying therapeutic mechanism. We find that BPNSs inhibit autophagy at an early stage via the AMPK-mTOR pathway, switch the energy metabolic pathway to oxidative phosphorylation, increase intracellular ATP levels, suppress apoptosis, reduce inflammation and oxidative stress, and down-regulate senescence-associated secretory phenotype (SASP)-related genes in rheumatoid arthritis synovial fibroblasts (RA-SFs). Further, BPNSs induce the apoptosis of macrophages and promote their transition from the M1 to the M2 phenotype by regulating related cytokines. Significantly, the administration of BPNSs can alleviate key pathological features of RA in mice, revealing great therapeutic potential. This study provides a novel option for treating RA, with BPNSs emerging as a promising therapeutic candidate.

Background: LncRNAs regulate tumorigenesis and development in a variety of cancers. We substantiate for the first time that LINC00606 is considerably expressed in glioblastoma (GBM) patient specimens and is linked with adverse prognosis. This suggests that LINC00606 may have the potential to regulate glioma genesis and progression, and that the biological functions and molecular mechanisms of LINC00606 in GBM remain largely unknown., Methods: The expression of LINC00606 and ATP11B in glioma and normal brain tissues was evaluated by qPCR, and the biological functions of the LINC00606/miR-486-3p/TCF12/ATP11B axis in GBM were verified through a series of in vitro and in vivo experiments. The molecular mechanism of LINC00606 was elucidated by immunoblotting, FISH, RNA pulldown, CHIP-qPCR, and a dual-luciferase reporter assay., Results: We demonstrated that LINC00606 promotes glioma cell proliferation, clonal expansion and migration, while reducing apoptosis levels. Mechanistically, on the one hand, LINC00606 can sponge miR-486-3p; the target gene TCF12 of miR-486-3p affects the transcriptional initiation of LINC00606, PTEN and KLLN. On the other hand, it can also regulate the PI3K/AKT signaling pathway to mediate glioma cell proliferation, migration and apoptosis by binding to ATP11B protein., Conclusions: Overall, the LINC00606/miR-486-3p/TCF12/ATP11B axis is involved in the regulation of GBM progression and plays a role in tumor regulation at transcriptional and post-transcriptional levels primarily through LINC00606 sponging miR-486-3p and targeted binding to ATP11B. Therefore, our research on the regulatory network LINC00606 could be a novel therapeutic strategy for the treatment of GBM., (© 2024. The Author(s).)

Pancreatic cancer, as one of the neoplasms with the highest degree of malignancy, has become a main disease of concerns in recent years. BHLHE40, a critical transcription factor for remodeling of the tumor immune microenvironment, has been described to be substantially increased in a variety of tumor-associated immune cells. Nevertheless, the pro-cancer biological functions and underlying molecular mechanisms of BHLHE40 for pancreatic cancer and its unique microenvironment are unclear. Hereby, we investigated the pro-oncogenic role of BHLHE40 in the pancreatic cancer microenvironment by bioinformatics analysis and cell biology experiments and determined that the expression of BHLHE40 was obviously elevated in pancreatic cancer tissues than in adjacent normal tissues. In parallel, Kaplan-Meier survival analysis unveiled that lower expression of BHLHE40 was strongly associated with better prognosis of patients. Receiver operating characteristic (ROC) curve analysis confirmed the accuracy of the BHLHE40-related prediction model. Subsequent, spearman correlation analysis observed that higher expression of BHLHE40 might be involved in immunosuppression of pancreatic cancer. Silencing of BHLHE40 could inhibit proliferation, invasion, and apoptosis of pancreatic cancer in vitro and in vivo, implying that BHLHE40 is expected to be a potential therapeutic target for pancreatic cancer. In addition, we explored and validated the FGD5-AS1/miR-15a-5p axis as a potential upstream regulatory mode for high expression of BHLHE40 in pancreatic cancer. In summary, our data showed that ceRNA involved in the regulation of BHLHE40 contributes to the promotion of immunosuppressive response in pancreatic and is expected to be a diagnostic marker and potential immunotherapeutic target for pancreatic cancer., (© 2023. Springer Nature Limited.)

Previous studies on the relationship between dietary minerals and preeclampsia (PE) have given inconsistent results. The aim of this study was to further clarify the relationship between dietary minerals intake and PE in Chinese pregnant women. In this study, 440 pairs of hospital-based preeclamptic and healthy women were matched 1:1. Dietary intake was obtained through a 78-item semi-quantitative food frequency questionnaire. Multivariate conditional logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). Restricted cubic splines were plotted to evaluate the dose-response relationship between dietary minerals intake and PE. This study found significant inverse associations for dietary intake of calcium, magnesium, phosphorus, iron, copper, manganese and zinc and the risk of PE in both univariate and multivariate models (all P- trend < 0.05). After adjusting for possible confounders, compared with the lowest quartile, the odds ratio of the highest quartile was 0.74 (95% CI 0.56-0.98) for calcium, 0.63 (95% CI 0.42-0.93) for magnesium, 0.45 (95% CI 0.31-0.65) for phosphorus, 0.44 (95% CI 0.30-0.65) for iron, 0.72 (95% CI 0.53-0.97) for copper, 0.66 (95% CI 0.48-0.91) for manganese and 0.38 (95% CI 0.25-0.57) for zinc. In addition, a reverse J-shaped relationship between dietary minerals intake and PE risk was observed (P-overall association < 0.05). In Chinese pregnant women, a higher intake of dietary minerals, including calcium, magnesium, phosphorus, copper, iron, manganese, and zinc was associated with a lower odds of PE., (© 2023. Springer Nature Limited.)

Background: Many studies have suggested that the serum concentrations of vitamin A (VA) and vitamin E (VE) influence preeclampsia (PE) risk in pregnant women. However, few studies have assessed whether dietary intake and serum concentrations of VA and VE are correlated with PE risk., Methods: A 1:1 matched case-control study was conducted to explore the association between the dietary intake and serum concentrations of VA and VE and the risk of PE in pregnant Chinese women. A total of 440 pregnant women with PE and 440 control pregnant women were included in the study. Dietary information was obtained using a 78-item semi-quantitative food frequency questionnaire. Serum concentrations of VA and VE were measured by liquid chromatography-tandem mass spectrometry., Results: Compared with the lowest quartile, the multivariate-adjusted odds ratios [95% confidence interval (CI)] of the highest quartiles were 0.62 (95% CI: 0.40-0.96, P trend = 0.02) for VA, 0.51 (95% CI: 0.33-0.80, P trend =0.002) for β-carotene, and 0.70 (95% CI: 0.45-1.08, P trend = 0.029) for retinol. Additionally, for serum VA and VE concentrations, the multivariate-adjusted odds ratios (95% CI) were 2.75 (95% CI: 1.24-6.13, P trend = 0.002) and 11.97 (95% CI: 4.01-35.77, P trend < 0.001), respectively. No significant association was seen between VE intake and PE risk., Conclusions: Dietary VA intake was negatively correlated with PE risk, and serum VA and VE concentrations were positively correlated with PE risk among pregnant Chinese women., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liu, Ma, Huang, Bo, Fu, Cao, Duan, Dou, Zeng, Wang, Gong, Zhang, Lyu and Zhao.)

Highly dispersed Cu@FeCo/rGO catalysts have been prepared by two-step reduction method and used for hydrogen production from ammonia borane (NH 3 BH 3 , AB) hydrolysis at 298 K. The activity and reusability of synthesized composite catalyst were much more higher than Cu@FeCo for AB hydrolysis dehydrogenation at 298 K. Kinetic study manifested that AB hydrolysis dehydrogenation with Cu@FeCo/rGO catalysts was approaching to the first order at different catalyst concentrations. The hydrolysis reaction completed within four minutes, and its maximum hydrogen production rate reached to 7863.0 ml min -1 g -1 at 298 K., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Many studies have suggested that folate plays a role in preeclampsia (PE) risks, but few studies have assessed folate-related 1-carbon metabolism (OCM)-related nutrients with the risk of PE. We hypothesized that OCM-related nutrients are associated with PE. A 1:1 matched case-control study was conducted to explore the association between dietary OCM-related nutrients intake and the risk of PE in pregnant Chinese women. Four hundred and forty pairs of pregnant women with PE and hospital-based, healthy pregnant women, matched according to gestational week (±1 week) and age (±3 years), were recruited. Dietary intake was assessed using a validated 78-item semiquantitative food frequency questionnaire. Multivariate conditional logistic regression was used to estimate odds ratios (ORs) and 95% CIs. Restricted cubic splines were plotted to evaluate the dose-response relationship between dietary OCM-related nutrient intake and the risk of PE. Intake of folate, vitamin B 6 , vitamin B 12 , methionine, and total choline were inversely related to the risk of PE after adjustment for covariates (all P trend < .05). Adjusted ORs (95% CIs) for quartile 4 versus quartile 1 were 0.71 (0.55-0.93) for folate, 0.66 (0.50-0.87) for vitamin B 6 , 0.68 (0.52-0.88) for vitamin B 12 , 0.77 (0.60-0.81) for methionine, and 0.67 (0.51-0.87) for total choline. This study suggests that dietary OCM-related nutrients intake is associated with lower odds of PE in pregnant Chinese women., Competing Interests: Author Declarations The authors declare no conflict of interest., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

The insulation state of high-voltage cables in coal mines directly influences the reliability of power supply in coal mines and the level of safe production. In this paper, the degradation mechanism of cable insulation is analyzed, and an online monitoring technology of cable insulation in coal mines based on decision tree is proposed, the technical principle of the judgment method of cable degradation based on decision tree is studied, the feasibility of this technology is verified through simulation, the existing online monitoring solutions for cable insulation are analyzed, and a wide-area synchronous measurement and monitoring system for cable insulation is designed. This technology has been applied in Chinese coal mine enterprises in China and achieved a good effect., Competing Interests: There are no potential competing interests in this paper. And all authors have seen the manuscript and approved to submit it to the journal. The authors confirm that the content of the manuscript has not been published or submitted for publication elsewhere., (Copyright © 2022 Wenjun Fu et al.)

Background: The effect of carotenoids on the risk of preeclampsia (PE) is uncertain. We aimed to examine the associations between the intake of dietary carotenoids and related compounds by pregnant women in China, and the risk of their developing PE., Methods: Four hundred and forty PE cases and 440 age- (± 3 years), gestational age- (± 1 weeks) and gestational diabetes mellitus status- (yes/no) matched healthy controls were recruited from March 2016 to June 2019. Dietary intake of carotenoids was assessed using a 79-item validated food-frequency questionnaire. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression., Results: After adjusting for potential confounders, we found that the intake of total carotenoids, β-carotene, β-cryptoxanthin, lycopene, and lutein and zeaxanthin (lut-zea) were negatively associated with the odds of developing PE. Compared with the lowest quartile intake, the multivariate-adjusted OR (95% CI) of the highest quartile intake was 0.29 (0.16-0.54, P trend  <  0.001) for total carotenoids, 0.31 (0.16-0.58, P trend  <  0.001) for β-carotene, 0.50 (0.27-0.90, P trend  = 0.007) for β-cryptoxanthin, 0.55 (0.30-0.99, P trend  = 0.04) for lycopene and 0.32 (0.17-0.61, P trend  = 0.001) for lut-zea. However, no significant associations were observed between the risk of developing PE and α-carotene intake (OR = 0.75, 95% CI: 0.41-1.36, P trend  = 0.28). Moreover, similar negative associations were found for every one-standard-deviation increase in the intake of total carotenoids, β-carotene, β-cryptoxanthin, lycopene and lut-zea., Conclusion: These results indicate that a high intake of total carotenoids, β-carotene, β-cryptoxanthin, lycopene and lut-zea may be associated with a low risk of developing PE., (© 2022. The Author(s).)

Little is known about the effects of dietary patterns on prevalent pre-eclampsia in Chinese population. This study aimed to investigate the associations between dietary patterns and the odds of pre-eclampsia among Chinese pregnant women. A 1:1 age- and gestational week-matched case-control study was conducted between March 2016 and February 2019. A total of 440 pairs of pre-eclampsia cases and healthy controls were included. Dietary intakes were assessed by a seventy-nine-item FFQ and subsequently grouped into twenty-eight distinct groups. Factor analysis using the principal component method was adopted to derive the dietary patterns. Conditional logistic regression was used to analyse the associations of dietary patterns with prevalent pre-eclampsia. We identified four distinct dietary patterns: high fruit-vegetable, high protein, high fat-grain and high salt-sugar. We found that high fruit-vegetable dietary pattern (quartile (Q)4 v. Q1, OR 0·71, 95 % CI 0·55, 0·92, Ptrend = 0·013) and high protein dietary pattern (Q4 v. Q1, OR 0·72, 95 % CI 0·54, 0·95, Ptrend = 0·011) were associated with a decreased odds of pre-eclampsia in Chinese pregnant women. Whereas high fat-grain dietary pattern showed a U-shaped association with pre-eclampsia, the lowest OR was observed in the third quartile (Q3 v. Q1, OR 0·75, 95 % CI 0·57, 0·98, Ptrend = 0·111). No significant association was observed for high salt-sugar dietary pattern. In conclusion, pregnancy dietary pattern characterised by high fruit-vegetable or high protein was found to be associated with a reduced odds of pre-eclampsia in Chinese pregnant women.

Objective: To explore the genetic basis for a child presented with renal failure and multi-cystic dysplastic kidney without anal atresia., Methods: Peripheral blood sample of the child and his parents were collected and subjected to whole exome sequencing. Candidate variant was verified by Sanger sequencing., Results: The 40-day-old infant had presented with vomiting brown matter in a 7 days neonate and was transferred for kidney failure. Clinical examination has discovered renal failure, polycystic renal dysplasia, congenital hypothyroidism, bilateral thumb polydactyly, sensorineural hearing loss and preauricular dermatophyte. Genetic testing revealed that he has harbored a previously unreported c.824delT, p.L275Yfs*10 frameshift variant of SALL1 gene, which was confirmed by Sanger sequencing as de novo., Conclusion: The patient was diagnosed with Townes-Brocks syndrome due to the novel de novo variant of SALL1 gene. Townes-Brocks syndrome without anal atresia is rare. Above finding has also enriched the mutational spectrum of the SALL1 gene.

Background: The DGKE gene encodes the diacylglycerol kinase epsilon (DGKε). Loss-of-function mutations of DGKE caused a group of rare renal diseases, which are called DGKE nephropathy. We report the clinical manifestations and therapeutic effects of a patient diagnosed with DGKE nephropathy., Case Report: The patient's initial symptoms were fever, diarrhea, eyelid edema, acute anemia, acute thrombocytopenia, an elevation of plasm D-dimer, proteinuria, microscopic hematuria, without oliguria or renal insufficiency at the age of 7.6 months. Hemolytic uremic syndrome was diagnosed. His proteinuria and hematuria turned out negative 2 months later. Proteinuria was noticed again at the age of 5.5-year old when he was brought to the hospital because of failure to thrive. Since then, he had been noticed with persistent proteinuria., Results: Genetic analysis revealed 2 novel heterozygous mutations on DGKE of the patient. Renal pathology mimicked membrane proliferative glomerulonephritis (MPGN)., Conclusions: After a 5-month treatment of cyclosporine A (CsA), proteinuria and hypoproteinemia have relieved apparently. We also observed an improvement of his growth., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: The suppressor of cytokine signaling 3 (SOCS3) is a specific negative regulator of signal transducer and activator of transcription 3 (STAT3) signaling, which is predominantly activated to induce neuroinflammatory response in microglia and functions essential roles during cerebral ischemia-reperfusion (I/R) injury. Constitutive photomorphogenesis 9 (COP9) signalosome (CSN) is a signaling platform controlling protein stability by remodeling of cullin-RING ubiquitin ligases, which is recently reported to specifically recognize proteins with SOCS-box domains. However, whether SOCS3 is related to COP9 signalosome in neuroinflammation during cerebral I/R injury is completely unclear., Methods: Mice subjected to transient middle cerebral artery occlusion (MCAO) and reperfusion, and BV2 microglia cells treated with oxygen-glucose deprivation and reoxygenation (OGD/R) were used to mimic cerebral I/R injury. Western blot, qRTPCR, immunofluorescence, and co-Immunoprecipitation assays were performed to explore the regulatory mechanism of SOCS3 on neuroinflammation and the relationship of SOCS3 and COP9 signalosome during cerebral I/R injury., Results: SOCS3 expression is significantly upregulated in microglia during OGD/R treatment, and overexpression of SOCS3 suppresses OGD/R-induced STAT3 activation and inflammatory factor expression. Furthermore, we find that COP9 signalosome subunit 3 (CSN3) interacts with SOCS3 protein to enhance its stability, thereby resulting in restricting OGD/R-induced STAT3 activation and inflammatory response. Moreover, we find that knockdown of CSN3 evidently accelerates STAT3 activation, and aggravates cerebral I/R injury in vivo., Conclusion: CSN3 restricts neuroinflammatory responses during cerebral I/R injury through stabilizing SOCS3 protein and indicates that CSN3 a potential therapeutic target for cerebral I/R injury., Competing Interests: The authors reported no conflicts of interest for this work., (© 2021 Liang et al.)

Atherosclerosis (AS)-related diseases remain among the leading causes of death worldwide. Modified Xiaoyaosan (also called Tiaogan-Liqi prescription, TGLQ), a traditional Chinese medical formulation, has been widely applied in the treatment of AS-related diseases. The aim of this study was to investigate the underlying pharmacological mechanisms of TGLQ in acting on AS. A total of 548 chemical compounds contained in TGLQ, and 969 putative targets, were collected from the Computation Platform for Integrative Pharmacology of Traditional Chinese Medicine, while 1005 therapeutic targets for the treatment of AS were obtained from the DisGeNET, TTD and CTD databases. Moreover, the 63 key targets were screened by the intersection of the targets above, and by network topological analysis. Further functional enrichment analysis showed that the key targets were significantly associated with regulation of the immune system and inflammation, improvement of lipid and glucose metabolism, regulation of the neuroendocrine system and anti-thrombosis effect. The in vivo experiments confirmed that TGLQ could reduce plasma lipid profiles and plasma inflammatory cytokines, and also inhibit AS plaque formation, within the AS model ApoE-/- mice. The in vitro experiments validated the hypothesis that TGLQ could significantly reduce intracellular lipid accumulation, suppress the production of inflammatory cytokines of macrophages induced by oxidized-LDL, and inhibit the protein expression of heat shock protein 90 and toll-like receptor 4. This study identified a list of key targets of TGLQ in the treatment of AS by applying an integrative pharmacology approach, which was validated by in vivo and in vitro experimentation.

Background: Gut microbiota has a number of essential roles in nutrition metabolism and immune homeostasis, and is closely related to hepatocellular progression. In recent years, studies have also shown that FK506 binding protein 5 (FKBP-5) plays a crucial role in immune regulation. However, it is not yet clear whether FKBP-5 promotes the development of hepatocellular carcinoma (HCC) by affecting immune function and gut microbiota., Methods: FKBP-5 expression was verified by immunochemistry and western blot and reverse transcription polymerase chain reaction (RT-qPCR) assays. After treatment in WT and FKBP-5 -/- mice, the histological characteristic of mice liver tissue was assessed by H&E staining, and hepatic leukocytes and hepatic NKT cells were identified by flow cytometer. Meanwhile, primary bile acids (BAs), secondary BAs, serum total cholesterol, and the weight of abdomen adipose tissues were examined, and the gut microbiota was evaluated by 16S ribosomal ribonucleic acid (rRNA) sequencing., Results: We discovered that FKBP-5 was highly expressed in HCC tissues. Meanwhile, FKBP-5 deletion inhibited tumor progression by increasing CD 8+ T, CD 4+ T, NKT and CD 4+ NKT cells in mice after diethylnitrosamine (DEN) injection. Besides, we proved that FKBP-5 deletion generated rapid and significant reductions in the intestinal BAs, the weight of abdomen adipose tissues and the serum total cholesterol. FKBP-5 deletion also led to a change in the composition of gut microbiota, suggesting that BAs are the main dietary factor regulating gut microbiota, which could be affected by FKBP-5 deletion. Further, we uncovered that anti-CD4 and anti-CD8 treatments facilitated hepatocellular progression by modulating gut microbiota composition in FKBP-5 -/- mice., Conclusions: Therefore, we demonstrated that FKBP-5 deletion inhibited hepatocellular progression by modulating immune response and gut microbiome-mediated BAs metabolism., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at: http://dx.doi.org/10.21037/jgo-21-71). The authors have no conflicts of interest to declare., (2021 Journal of Gastrointestinal Oncology. All rights reserved.)

Atherosclerosis (AS), the most common underlying pathology for coronary artery disease, is a chronic inflammatory, proliferative disease in large- and medium-sized arteries. The vascular endothelium is important for maintaining vascular health. Endothelial dysfunction is a critical early event leading to AS, which is a major risk factor for stroke and myocardial infarction. Accumulating evidence has suggested the critical roles of histone deacetylases (HDACs) in regulating vascular cell homeostasis and AS. The purpose of this review is to present an updated view on the roles of HDACs (Class I, Class II, Class IV) and HDAC inhibitors in vascular dysfunction and AS. We also elaborate on the novel therapeutic targets and agents in atherosclerotic cardiovascular diseases., (Copyright © 2020 Chen, He, Fu, Sahebkar, Tan, Xu and Li.)

Background: Previous studies have reported that Xiaoyaosan (XYS), Tiaogan-Liqi therapy, has a protective function in depressive disorder, and can regulate body weight and corticosterone (CORT) level. However, little is known about the effect of XYS in treating atherosclerosis. This study aimed to explore the influence XYS on macrophage foam cell formation and related mechanism., Methods: Rat peritoneal macrophages (PMs) were separated and stimulated with CORT and oxidized low density lipoprotein (ox-LDL). The serum was obtained from rats treated with different doses of XYS and was added into the medium for macrophages. Then, the cell activity and lipid content of PMs were measured through Cell Counting Kit-8 (CCK-8) assay and oil red staining, respectively. The expressions of glucocorticoid receptor (GR), ATP binding cassette subfamily A member 1 (ABCA1), and heat shock protein 90 (HSP90) were detected. In addition, overexpression of GR and ABCA1 was performed and the effect on XYS treatment was subsequently assessed., Results: The CCK-8 assay showed the serum increased cell activity of CORT-induced stress PMs in a XYS dose-dependent manner. Oil red staining and enzyme-linked immunosorbent assay (ELISA) showed that the serum decreased lipids of PMs. In the XYS treated groups, HSP90 protein was decreased and protein levels of ABCA1 and GR were increased in cytoplasm, while GR protein in nucleus was decreased. Co-immunoprecipitation (Co-IP) assay indicated GR might interact with HSP90 and be involved with the function of XYS. Furthermore, overexpression of GR attenuated the protective function of XYS on CORT-induced stress in PMs, while overexpression of ABCA1 enhanced that., Conclusions: This study denoted that XYS could protect PMs from CORT-induced stress by regulating the interaction of GR and ABCA1, which might contribute to the treatment of atherosclerosis., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-6505). The authors have no conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)

Maternal diet is an important potential factor associated with the risk of preeclampsia. However, it is unclear whether adherence to a Dietary Approaches to Stop Hypertension (DASH)-style diet can reduce the development of preeclampsia. To examine the potential association, we conducted a hospital-based case-control study at the First Affiliated Hospital of Zhengzhou University, China. A total of 449 cases with preeclampsia and 449 controls were studied. Dietary information was collected using a validated food frequency questionnaire (FFQ). DASH scores were calculated according to nutrients/food emphasised or minimised in the DASH diet. The calculated DASH scores ranged from 11 to 38 for all of the participants, and the DASH scores of the cases were significantly lower than those of the controls (23.48 ± 4.58 vs 24.51 ± 4.51; p = 0.001). Participants in the fourth quartile of the DASH score were 45% less likely to have preeclampsia than those in the first quartile in the crude model (Q4 vs Q1, odds ratio [OR]: 0.55; 95% confidence interval [CI]: 0.38, 0.80; p trend  = 0.001). The relationship remained significant in the model adjusted for multiple confounders, especially for major risk factors of preeclampsia (OR: 0.53; 95% CI: 0.36, 0.78; p trend  = 0.001). Our findings suggest an inverse relationship between adherence to a DASH-style diet and the odds of preeclampsia. Further larger-scale cohort studies or randomised controlled trials are warranted to confirm these relationships.

Background: Premature ventricular complex (PVC) with narrow QRS duration originating from proximal left anterior fascicle (LAF) is challenging for ablation. This study was performed to evaluate the safety and feasibility of ablation from right coronary cusp (RCC) for proximal LAF-PVC and to investigate this PVC's characteristics., Methods: Mapping at RCC and left ventricle and ECG analysis were performed in 20 patients with LAF-PVC., Results: The earliest activation site (EAS), with Purkinje potential during both PVC and sinus rhythm, was localized at proximal LAF in 8 patients (proximal group) and at nonproximal LAF in 12 patients (nonproximal group). The Purkinje potential preceding PVC-QRS at the EAS in proximal group (32.6±2.5 ms) was significantly earlier than that in nonproximal group (28.3±4.5 ms, P =0.025). Similar difference in the Purkinje potentials preceding sinus rhythm QRS at the EAS was also observed between proximal and nonproximal groups (35.1±4.7 versus 25.2±5.0 ms, P <0.001). In proximal group, the distance between the EAS to left His bundle and to RCC was shorter than that of nonproximal group (12.3±2.8 versus 19.7±5.0 mm, P =0.002, and 3.9±0.8 versus 15.7±7.8 mm, P <0.001, respectively). No difference in the distance from RCC to proximal LAF was identified between the 2 groups. PVCs were successfully eliminated from RCC for all proximal groups but at left ventricular EAS for nonproximal groups. The radiofrequency application times, ablation time, and procedure time of nonproximal group were longer than that of proximal group. Electrocardiographic analysis showed that, when compared with nonproximal group, the PVCs of proximal group had narrower QRS duration; smaller S wave in leads I, V 5 , and V 6 ; lower R wave in leads I, aVR, aVL, V 1 , V 2 , and V 4 ; and smaller q wave in leads III and aVF. The QRS duration difference (PVC-QRS and sinus rhythm QRS) <15 ms predicted the proximal LAF origin with high sensitivity and specificity., Conclusions: PVCs originating from proximal LAF, with unique electrocardiographic characteristics, could be eliminated safely from RCC.

Blood-brain barrier (BBB) is a barrier which maintains the material exchange balance of brain microenvironment and could be destroyed by chronic stress (CS). Glucocorticoids (GCs) can mimic the chronic stress induced damage to BBB. GCs induced BBB trauma models in vitro and in vivo to explore the effects of the traditional medicine Xiao-Yao-San (XYS). In this research, we found CS could injure the BBB to change the biochemical index, which could be reversed by XYS in vitro. The abilities of cell proliferation, invasion, and the expression of tight junction related genes (Occludin, Claudin, JAM-1 and ZO-1) were suppressed by CS and the trauma could be reversed by XYS partly. It was showed that GRs interacted with Occludin directly and inhibited Occluding expression. In rats BBB trauma model, the GC content was deceased and BBB permeability was repaired by XYS. The expression of Occludin, Claudin, JAM-1 and ZO-1 were increased in the treatment of XYS. In our research, it shown that XYS affect the content of the GC and GR which interacted with Occludin directly for the first time. In addition, we also found that XYS could reduce BBB injury induced by CS via GR in BBB model in vitro. Therefore, it proves that XYS is a potential BBB repair medicine and may help to elucidate mechanism of brain pathology., (Copyright © 2019 Elsevier B.V. All rights reserved.)

To ensure that the shaft boring machine (SBM) runs along the pre-designed axis steadily, the role of the attitude measurement system is essential, but its accuracy and reliability cannot be guaranteed. Currently, there is no effective technology to meet the actual requirements, and there is a lack of relevant theoretical research in this field. Through further study of the attitude analysis method and multi-sensor fusion technology, this paper presents a dual coordinate method, which can be used to describe the attitude characteristics of the SBM. Moreover, this paper discusses the relationships between the attitude changes and the values of the angle as well as displacement and analyzes the implementation complexity and computational efficiency of related algorithms in software and hardware. According to the working characteristics of the SBM, the hardware design and the reasonable layout of the attitude measurement system are provided. Based on multi-sensor data, this paper puts forward an improved method combining a complementary filter with an extended Kalman filter (EKF) for attitude estimation and error compensation. The simulation experiments of different working processes verify the steady-state response and dynamic response performance of the method. Experimental results show that the dual coordinate method and the proposed filter are more suitable for attitude estimation of the SBM compared to other methods., Competing Interests: The authors declare no conflict of interest.

Atherosclerosis is a metabolic and chronic inflammatory disease caused by deposition of lipoproteins in arteries. However, the diagnostic drug and the mechanism for this vascular disease are less studied. In the present study, atherosclerosis model was developed using apolipoprotein E-deficient mice that was treated with long-term high-fat food and chronic stresses. Xiaoyaosan (XYS) and glucocorticoid receptor (GR) antagonist RU 38486 were orally administrated to the mice. The change of aortic root vessels was observed by histological analysis. The results indicate that high-fat food coupled with chronic stress induced atherosclerosis in mice model, with plaque formation in the entire aortas foam cells and macrophage infiltration in aortic tissues. However, XYS granules inhibited the development of atherosclerotic lesion, with down-regulation of GC, TC, TG, HDL-C, ox-LDL, LDL-C, IFN-γ, IL-6, IL-1β, and TNF-α measured by ELISA method; XYS inhibited the expressions of GR, CD36, HSP27/60/90, and induced ABCA1 in atherosclerotic mice, which was measured by qPCR and Western blot, which showed similar effect as positive control RU 38486 did. The interaction between HSP90-GR complexes and CD36 was validated in atherosclerotic mice. Our results inferred that the HSP/GR complex-mediated CD36 axis was involved in the regulation of atherosclerosis development in mice verified by Co-IP assay, EMSA, and Chip-PCR. These findings not only provide the potential therapeutic value of Xiaoyaosan for atherosclerotic vulnerable plaque but also brought forth a novel strategy for preventing the formation and treatment of atherosclerotic vulnerable plaques through the elucidated mechanism of XYS on vulnerable plaque., Competing Interests: None., (AJTR Copyright © 2019.)

Objective: To investigate the relationship between dietary intake during the third trimester and preeclampsia., Methods: A case-control study with 1∶1 matching was performed. A total of 131 patients with preeclampsia hospitalized in the First Affiliated Hospital of Zhengzhou University from March 2016 to December 2016 were selected as the case group. According to age ±3 years and gestational age ±2 weeks, 131 pregnant women with normal blood pressure and no proteinuria in the hospital were randomly selected as the control group. The questionnaires of food frequency and gestational health risk factors in the past three months were conducted and the average daily intakes of various nutrients were calculated. Conditional Logistic regression was applied to analyze the data., Results: Multivariate conditional Logistic regression showed that pre-pregnancy body mass index(OR=1. 18, 95%CI 1. 08-2. 82) and gestational weight gain(OR=1. 51, 95%CI 1. 15-1. 97) were higher, while the intakes of red and/or yellow fruits(OR=0. 76, 95%CI 0. 60-0. 98), and dietary vitamin C(OR=0. 57, 95%CI 0. 33-0. 99) and folic acid(OR=0. 36, 95%CI 0. 18-0. 72) were lower in case group than that in control group(P<0. 05)., Conclusion: Higher pre-pregnancy body mass index and over gestational weight gain are the risk factors for pre-eclampsia. Appropriate increase of red and/or yellow fruit intake during pregnancy may be beneficial to prevent pre-eclampsia. Vitamin C and folic acid intake might be protective factors for pre-eclampsia. .

Recent researches have shown that autophagy is associated with the pathogenesis of neurodegenerative disorders, but there is no paper to investigate the effects of autophagy modulation on Parkinson's disease depression (PDD). In addition, glycyrrhizic acid (GA), the major bioactive ingredient of Radix glycyrrhizae, can induce autophagy and ease rotenone-induced Parkinson's disease (PD). However, there is also no paper to study the action and molecular mechanisms of GA on PDD. In this research, we built the injury model of SH-SY5Y cells through 6-hydroxydopamine (6-OHDA) and corticosterone (CORT). Then, our results showed that GA markedly increased the viability and decreased the apoptosis in SH-SY5Y cells after pre-treating with 6-OHDA and CORT. Moreover, GA notably decreased the expressions of α-Syn and p-S1292-LRRK2 proteins, and significantly increased the levels of CREB and BDNF proteins. Previous papers have suggested that CORT contributed to dopaminergic neurodegeneration via the glucocorticoid (GC)/glucocorticoid receptor (GR) interaction, and our results showed that GA reduced GC level and hypothalamic-pituitary-adrenal (HPA) activity in SH-SY5Y cells by regulating GR signaling pathway. Furthermore, mechanism investigations also showed that GA had the ability to up-regulate the conversion of LC3B II/I and the expression of Beclin-1, and induce autophagy in SH-SY5Y cells, which were reversed by the autophagy inhibitor 3-methyladenine (3-MA). Collectively, these findings proved that GA exerted efficient activity against neurotoxicity in SH-SY5Y cells induced by 6-OHDA and CORT via activation of autophagy, which should be developed as an efficient candidate for treating PDD in the future.

Background: Depression is characterized by a pathological injury to the hippocampal neurons. Senkyunolide A (SenA) is one of the major active components of Dan-zhi-xiao-yao-san, which is widely used in the treatment of depression-related disorders., Materials and Methods: In the present study, it was hypothesized that the antidepressant effect of Dan-zhi-xiao-yao-san depended on the function of SenA and the authors attempted to reveal the molecular mechanism associated with the treatment. An in vitro depression model was induced using corticosterone (Cort), and the effect of SenA on the cell viability, apoptosis, and protein phosphatase 2A/α-synuclein (PP2A/α-syn) signaling was detected. To validate the mechanism driving the therapeutic effect of SenA, activity of PP2A and α-syn was modulated and the effect on neural cells was evaluated., Results: The results showed that SenA protects Cort-induced cell apoptosis in PC12 cells. In addition, SenA increased Cort-induced reduction of PP2A activity, while it decreased the expression of p-PP2A, α-syn, and p-α-syn (Ser129). Further, modulation of PP2A activity with specific inhibitor okadaic acid (OA) increased Cort-induced cell apoptosis, while PP2A activator D-erythro-sphingosine (SPH) exhibited an opposite effect. The neuroprotective effects of SenA on neural cells also depended on inhibition of α-syn function, the regulation of which would influence the activity of PP2A in a negative loop., Conclusion: Collectively, the results suggested that the neuroprotective effects of SenA were exerted by modulating activities of PP2A activities and α-syn. The findings partially explained the mechanism associated with the neuroprotective effect of SenA., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Objective: Intracerebral hemorrhage (ICH) is one of the most common acute cerebrovascular diseases with high mortality. Numerous studies have shown that inflammatory response played an important role in ICH-induced brain injury. Theaflavin (TF) extracted from black tea has various biological functions including anti-inflammatory activity. In this study, we investigated whether TF could inhibit ICH-induced inflammatory response in rats and explored its mechanism., Materials and Methods: ICH rat models were induced with type VII collagenase and pretreated with TF by gavage in different doses (25 mg/kg-100 mg/kg). Twenty-four hours after ICH attack, we evaluated the rats' behavioral performance, the blood-brain barrier (BBB) integrity, and the formation of cerebral edema. The levels of reactive oxygen species (ROS) and inflammatory cytokines were examined by 2',7'-dichlorofluorescin diacetate and enzyme-linked immunosorbent assay. Nissl staining and transferase dUTP nick end labeling (TUNEL) were aimed to detect the neuron loss and apoptosis, the mechanism of which was explored by Western blot., Results: It was found that in the pretreated ICH rats TF significantly alleviated the behavioral defects, protected BBB integrity, and decreased the formation of cerebral edema and the levels of ROS as well as inflammatory cytokines (including interleukin-1 beta [IL-1β], IL-18, tumor nectosis factor-alpha, interferon-γ, transforming growth factor beta, and (C-X-C motif) ligand 1 [CXCL1]). Nissl staining and TUNEL displayed TF could protect against the neuron loss and apoptosis via inhibiting the activation of nuclear transcription factor kappa-β-p65 (NF-κβ-p65), caspase-1, and IL-1β. We also found that phorbol 12-myristate 13-acetate, a nonspecific activator of NF-κβ-p65, weakened the positive effect of TF on ICH-induced neural defects and neuron apoptosis by upregulating NF-κβ-related signaling pathway., Conclusion: TF could alleviate ICH-induced inflammatory responses and brain injury in rats via inhibiting NF-κβ-related pathway, which may provide a new way for the therapy of ICH., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Stress-induced cellular defense machinery has a critical role in mediating cancer drug resistance, and targeting stress-related signaling has become a novel strategy to improve chemosensitivity. Betulinic acid (BA) is a naturally occurring pentacyclic triterpenoid with potent anticancer bioactivities in multiple malignancies, whereas its underlying mechanisms remain unclear. Here in, we found that BA has synergistic effects with taxol to induce breast cancer cells G2/M checkpoint arrest and apoptosis induction, but had little cytotoxicity effects on normal mammary epithelial cells. Drug affinity responsive target stability (DARTS) strategy further identified glucose-regulated protein 78 (GRP78) as the direct interacting target of BA. BA administration significantly elevated GRP78-mediated endoplasmic reticulum (ER) stress and resulted in the activation of protein kinase R-like ER kinase (PERK)/eukaryotic initiation factor 2a/CCAAT/enhancer-binding protein homologous protein apoptotic pathway. GRP78 silencing or ER stress inhibitor salubrinal administration was revealed to abolish the anticancer effects of BA, indicating the critical role of GRP78 in mediating the bioactivity of BA. Molecular docking and coimmunoprecipitation assay further demonstrated that BA might competitively bind with ATPase domain of GRP78 to interrupt its interaction with ER stress sensor PERK, thereby initiating the downstream apoptosis cascade. In vivo breast cancer xenografts finally validated the chemosensitizing effects of BA and its biofunction in activating GRP78 to trigger ER stress-mediated apoptosis. Taken together, our study not only uncovers GRP78 as a novel target underlying the chemosensitizing effects of BA, but also highlights GRP78-based targeting strategy as a promising approach to improve breast cancer prognosis.

In modern society, fierce competitions cause yearly increase of depression and anxiety. Xiaoyao San is a traditional Chinese medicine which relieves depression and nourishes liver. The active ingredients contain saikoside A, saikoside C, saikoside D, ferulic acid, ligustilide, Atractylenolide I, Atractylenolide II, Atractylenolide Ⅲ, paeoniflorin, Albiflorin, liquiritin, glycyrrhizic acid and pachymic acid. In stress condition, glucocorticoid receptors participate in the hypothalamus-pituitarium-adrenal gland (HPA) axis to regulate the balance of organism. In response to stress, the HPA axis (hypothalamus-pituitarium-adrenal gland) is activated and the levels of glucocorticoid (GC) and catecholamine (CA) are increased to enhance neuroendocrine reactions. Chronic stress activates HPA axis and sustaining increase of GC, reduces the expression amount of GR and inhibits the mechanism of negative feedback on HPA. The lower negative feedback on HPA could lead to ketonemia. Several active ingredients of Xiaoyao San can raise the expression of GR and recover the negative feedback of HPA axis to relieve depression and illness state. In spite of the poor understanding of the current effective components in Xiaoyao San, this will be the focus of our further research. The study of Xiaoyao San could help us better understand its anti-depression mechanism and cure the patients.

Diabetic cardiomyopathy (DCM) is one of the main cardiac complications among diabetic patients. According to previous studies, the pathogenesis of DCM is associated with oxidative stress, apoptosis and proliferation of local cardiac cells. It showed, NRG1 can improve the function of mitochondria, and thereby, increasing proliferation and decreasing apoptosis of cardiac muscle cell via ErbB/AKT signaling, also, exert antioxidative function. Besides, NRG1/ErbB pathway was impaired in the DCM model which suggested this signaling played key role in DCM. Astraglaus polysaccharide (APS), one of the active components of Astragalus mongholicus, showed striking antioxidative effect. Here, in this study, our data showed that APS can promote proliferation and decrease apoptosis in AGE-induced DCM cell model, besides, APS can decrease intracellular ROS level, increase activity of SOD, GSH-Px and lower level of MDA and NO in DCM cell model, indicating APS exerted antioxidative function in DCM model cells. Besides, western blot results revealed APS induced NRG1 expressing and the phosphorylation level of ErbB2/4. In addition, the elevated NRG1 promoted AKT and PI3k phosphorylation which indicated APS may exert its function by NRG1/ErbB and the downstream AKT/PI3K signaling. Canertinib is ErbB inhibitor. The effect of APS on proliferation, apoptosis, antioxidation and NRG1/ErbB pathway was partly abolished after the cells were co-treated with APS and canertinib. Taken together, these results suggested APS may display its protective function in DCM cells by activating NGR1/ErbB signaling pathway. And our study increased potential for prevention and therapy to DCM.

Recent studies have evaluated the associations between polymorphisms of glucocorticoid receptor genes and asthma. However, the conclusions of these studies are conflicting. The objective of this meta-analysis was to clarify the association between all known polymorphisms of glucocorticoid receptor genetic loci and susceptibility to asthma, based on existing reports. We conducted a meta-analysis of the association between glucocorticoid receptor polymorphisms (NR3C1) and asthma risk. A systematical literature search was performed in PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure (CNKI), and Cochrane Library until January 15, 2018. The odds ratio (OR), 95% confidence interval (CI), and P value were calculated using Mantel-Haenszel statistics under the allele, homozygote, heterozygote, dominant, or recessive models. P values of less than 0.05 were considered to represent statistically significant associations between glucocorticoid receptor gene polymorphisms and asthma. All statistical analyses were done using the "meta" package (version 4.9-0) of R version 3.4.3 and RStudio version 1.0.44. A total of fourteen studies, reported via ten articles from online databases were included in our meta-analysis. For BclI (from eight studies), a significant association was detected in the allele model, homozygote model, and recessive model (C versus G: OR (95% CI) = 0.63 (0.40-0.97), CC versus GG: OR (95% CI) = 0.41(0.17-0.97), CC versus GC + GG: OR (95% CI) = 0.54(0.34-0.88)), but not in the heterozygote model or the dominant model. For ER22/23EK (from four studies), TthIII1 (from two studies), no significant association was found for any genetic model. After subgroup analyses by age, significant associations were observed for the allele model, homozygote model, dominant model and recessive model for BclI in adults. The ER22/23EK and TthIII1 polymorphisms were not found to be associated with susceptibility to ASTHMA; however, the BclI polymorphisms were significantly associated with ASTHMA in adults.

Alzheimer's disease (AD) is the most common type of dementia. Amyloid-β (Aβ)-induced neurodegeneration is hypothesized to be the primary pathological mechanism of AD. Tongluo Xingnao effervescent tablets (TXET), based on the traditional Chinese formula Qionggui Tang, have been used to treat AD and other types of dementia in China for decades. In the present study, the effects of TXET on cognition deficit, amyloid-β production, amyloid precursor protein procession and β-secretase expression were investigated in the APPswe/PS1dE9 mouse model of AD. As expected, APPswe/PS1dE9 mice exhibited cognitive decline and higher levels of Aβ and plaques in the brain compared with normal mice; however, these changes were attenuated following TXET treatment. Levels of C-terminal fragment (CTF)-β protein were decreased following treatment with TXET; however, CTF-α levels were unaffected. Furthermore, TXET treatment did not decrease γ-secretase activity or levels of presenilin-1 (PS1), neprilysin or insulin-degrading enzyme. These results indicate that TXET may regulate Aβ metabolism by downregulating the expression of β-secretase. The results of the present study have laid the foundation for the development of a Chinese medicinal compound with a β-secretase inhibitor as the target for the treatment of AD.

Polycyclic aromatic hydrocarbons (PAHs) can enter intertidal zones by various pathways and pose potential threats to intertidal ecosystem. We investigated distribution, composition, sources and risk assessment of PAHs in intertidal surface sediments of Bohai Bay. Total PAH concentrations ranged from 37.2ng·g -1 to 206.6ng·g -1 , among which high values occurred near Nanpaishuihe River Estuary and Haihe River Estuary. The composition patterns of PAHs were characterized by the predominance of 3-ring and 4-ring PAHs, and acenaphthylene was the most dominant component. Diagnostic ratios and principal component analysis have confirmed that PAH contaminants originated from mixed sources, and the major was local combustion. The mean benzo(a)pyrene equivalent concentration of total PAHs in intertidal sediments was 15.67ng·g -1 , which was mostly contributed by seven carcinogenic PAHs. According to ecological risk assessment, negative effects related to acenaphthylene would occur occasionally in partial survey regions of the study., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Tongluo Xingnao Effervescent Tablet (TXET), a traditional Chinese herbal formula composed of Ligusticum chuanxiong hor, Scutellaria baicalensis Georgi and Angelica sinensis, has been widely used to treat Alzheimer's disease (AD) and related dementias for decades in China. In the present study, we investigated the effects of TXET on mitochondrial function, energy metabolism and cognitive amelioration in the APPswe/PS1De9 transgenetic mouse model of AD. The energy charge and phosphocreatine, activity of the mitochondrial electron transport chain complexes, mitochondrial membrane potential, activity of Na(+)-K(+) ATPase and the expression levels of Bcl-2 and Bax in the brains were measured, respectively. TXET exhibits significant protection on mitochondrial function and energy supply in addition to ameliorating cognitive decline in APPswe/PS1De9 mice. TXET rescues mitochondrial function by increasing the mitochondrial membrane potential, energy charge levels, activity of respiratory chain complexes and Na(+)-K(+) ATPase activity. These findings suggest that TXET may attenuate cognition impairment through the restoration of mitochondrial function and energy metabolism in the brains in APPswe/PS1De9 mice., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Previous studies have revealed that uncontrollable stress can impair the synaptic plasticity and firing property of hippocampal neurons, which influenced various hippocampal-dependent tasks including memory, cognition, behavior, and mood. In this work, we had investigated the effects and mechanisms of the Chinese herbal medicine Xiao Yao San (XYS) against corticosterone-induced stress injury in primary hippocampal neurons (PHN) cells. We found that XYS and RU38486 could increase cell viabilities and decrease cell apoptosis by MTT, immunofluorescence, and flow cytometry assays. In addition, we observed that XYS notably inhibited the nuclear translocation of GR and upregulated the mRNA and protein expressions levels of Caveolin-1, GR, BDNF, TrkB, and FKBP4. However, XYS downregulated the FKBP51 expressions. Furthermore, the results of the electrophoretic mobility shift assay (EMSA) and double luciferase reporter gene detection indicated that FKBP4 promotes the transcriptional activity of GR reaction element (GRE) by binding with GR, and FKBP51 processed the opposite action. The in vivo experiment also proved the functions of XYS. These results suggested that XYS showed an efficient neuroprotection against corticosterone-induced stress injury in PHN cells by upregulating GRE transcriptional activity, which should be developed as a potential candidate for treating stress injury in the future.

Ligustrazine, also known as 2,3,5,6-tetramethylpyrazine (TMP), one of the major active compounds of Ligusticum wallichii Franchat., has been shown to reduce neuroinflammation and protect neurons during cerebral ischemia/reperfusion injury. However, whether it reduces blood-brain barrier (BBB) permeability during ischemic stroke is unclear. The aim of the present study was to investigate the role that TMP plays in protecting the BBB integrity in ischemia/reperfusion injury and to investigate the relevant mechanisms involved. Rats received an intraperitoneal injection of 20 mg/kg TMP 15 min before the onset of ischemia, which was induced by middle cerebral artery occlusion. Infarct volume, neurological score, brain edema, BBB permeability and tight junction protein impairment were observed. The results showed that TMP reduced the neurological score and levels of brain infarction and edema. In addition, TMP significantly decreased BBB permeability and prevented the impairment of occludin and claudin-5, two tight junction protein components of the BBB, in rat brains with ischemia/reperfusion injury. In addition, the expression and activity of matrix metalloproteinases, enzymes responsible for the degradation of the extracellular matrix and tight junctions, were reduced in the rat brains by TMP treatment. These results combined suggest that TMP reduces BBB permeability as well as neuronal damage in focal cerebral ischemia/reperfusion injury in rats.

The kinetics of abiotic reduction of mono-nitro aromatic compounds (mono-NACs) catalyzed by activated carbon (AC) in an anaerobic system were examined. There were 6 types of substituent groups on nitrobenzene, including methyl, chlorine, amino, carboxyl, hydroxyl and cyanogen groups, at the ortho, meta or para positions. Our results showed that reduction followed pseudo-first order reaction kinetics, and that the rate constant (logkSA) varied widely, ranging between -4.77 and -2.82, depending upon the type and position of the substituent. A quantitative structure-activity relationship (QSAR) model using 15 theoretical molecular descriptors and partial-least-squares (PLS) regression was developed for the reduction rates of mono-NACs catalyzed by AC. The cross-validated regression coefficient (Qcum(2), 0.861) and correlation coefficient (R(2), 0.898) indicated significantly high robustness of the model. The VIP (variable importance in the projection) values of energy of the lowest unoccupied molecular orbital (ELUMO) and the maximum net atomic charge on the aromatic carbon bound to the nitro group (QC(-)) were 1.15 and 1.01, respectively. These values indicated that the molecular orbital energies and the atomic net charges might play important roles in the reduction of mono-NACs catalyzed by AC in anaerobic systems., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

In this paper, three types of black carbons (BCs) named R-BC, W-BC, and C-BC were derived from rice straw ashes, wheat straw ashes, and corn straw ashes, respectively. Under room temperature and in an anaerobic aqueous solution, these three types of BCs could catalyze the reduction of nitrobenzene (NB) by sulfides rather than only act as the superabsorbent. The catalytic activities of BCs derived from different crop-residue ashes were very different and in the order of R-BC > W-BC > C-BC, since the reaction rate constants (k obs) of NB with the BCs in the presence of 3 mM sulfides were 0.0186, 0.0063, and 0.0051 h(-1), respectively. The key catalytic active sites for NB reduction were evaluated, with four types of modified BCs and two types of tailored graphite as the model catalysts. The results indicated that BCs probably had two types of active sites for NB reduction, the microscopic graphene moieties and the surface oxygen functional groups. Since the sulfides and BCs often coexist in the environment, this BC-catalyzed reduction technology of NACs may be applied as an in situ remediation technique without the need for reagent addition.

The occurrence of four antibiotics, including oxytetracycline (OTC), tetracycline (TC), norfloxacin (NOR) and ofloxacin (OFL), in surface water, overlying water, pore water and sediment samples were studied in the Baiyangdian Lake from February to November in 2009. The total concentrations of these antibiotics ranged among 17.73-281.82, 22.98-258.45, 22.43-198.95 ng L(-1) and 131.65-750.27 ng g(-1) in surface water, overlying water, pore water and sediments, respectively. Seasonal variation might be impacted by the frequency of different pattern of antibiotics and the water temperatures of different seasons, where the higher concentrations appeared at different seasons. In addition, the regions with significant sewage discharge or human agricultural activities exhibited high concentrations of antibiotics in water and sediments. The highest accumulation rates of the four antibiotics ranged from 11.27 to 29.71%, which indicated that these compounds exhibited strong adsorption to the sediment. However, higher concentrations of antibiotics in pore water and even overlying water may result in the release of these compounds from the sediment acting as a secondary contaminant source in a certain time period, especially for TC. The pseudo-partitioning values of fluoroquinolones (FQs) ranged from 4493 to 47,093 L kg(-1) and were much higher than those of tetracyclines (TCs), which ranged from 277 to 1880 L kg(-1) indicating that the FQs are prone to accumulation in the sediment., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Toxicity of organic extracts from the Pearl River sediments was investigated with Xenopus laevis embryos. The effects of sediment organic extracts on the mortality, body length and malformation of X. laevis embryos were tested by the Frog Embryo Teratogenesis Assay-Xenopus (FETAX). The 96-h LC₅₀ values for X. laevis embryos ranged from 62 to 137 g/L (g extracted sediment per L), and the toxicity effect on body length of larvae was not significant under 20 g/L. However, the teratogenic effects produced by sediment organic extracts were diverse, including edema, hypopigmentation, cardiac and ocular malformations, abdomen recurved and curved spine. The percentage of malformations increased with increasing sediment organic extracts, and even reached almost 100% at 10 and 20 g/L in Guangzhou district. A gradient of pollution in the Pearl River sediments was discerned from the teratogenic toxicity. Guangzhou district showed higher teratogenic toxicity compared with Panyu and Nansha districts as a possible consequence of high levels of PAHs, PCBs, OCPs and NP in the sediments. The teratogenic effects of organic extracts from the Pearl River sediments were successfully assessed which indicated the feasibility of teratogenic potential studies of sediments using X. laevis embryos., (Copyright © 2013. Published by Elsevier B.V.)

The mechanism of how endoparasitoids avoid the host's cellular immune reaction is not well known. Evidence is presented here for the existence of a Helix pomatia lectin binding protein (HpLBP) on Macrocentrus cingulum extraembryonic membrane and its involvement in the protection of embryos against encapsulation by its host Ostrinia furnaclis. HpLBP is present in eggs, embryos and larvae and is located on the outmost layer of the extraembryonic membrane. While Sephadex A-25 beads and immature Macrocentrus eggs coated with follicular cells were encapsulated, Macrocentrus embryos were not after they were transplanted separately into naive O. furnaclis larvae. Moreover, embryos became encapsulated after being coated with anti-HpLBP serum. Furthermore, encapsulation of agarose-H. pomatia lectin beads decreased significantly after the beads were coated with HpLBP. However, encapsulation of the HpLBP-coated agarose beads increased and the extent of encapsulation was enhanced significantly when the HpLBP-coated beads were pre-incubated with anti-HpLBP antibody.

Honey bees have a highly developed nest homeostasis, for example, maintaining low CO2 levels and stable nest temperatures at 35 degrees C.We investigate the role of nest homeostasis in deactivating phenolic compounds present in the nectar of Aloe littoralis. We show that the phenolic content in nectar was reduced (from 0.65% to 0.49%) after nectar was incubated in a nest of Apis cerana, and that it was reduced still more (from 0.65% to 0.37%) if nectar was mixed with hypopharyngeal gland proteins (HGP) of worker bees before being placed inside a nest. HGP had little effect on samples outside a nest, indicating that nest conditions are necessary for HGP to deactivate phenolics in nectar. Consequently, the highly controlled nest homeostasis of honey bees facilitates direct deactivation of phenolics in nectar, and plays a role in the action of HGP as well.