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• An advanced dementia prognostic tool (ADEPT) was used to predict 2-year survival. • Patients had higher mean ADEPT scores but lower mortality. • ADEPT cutoff score 11.2 has diagnostic reference value for survival prediction. • There was no difference in survival prediction between hospitals and nursing homes. • Filial piety and other factors generate positive treatment attitude. In this prospective study, we evaluated the usefulness of the advanced dementia prognostic tool (ADEPT) for estimating the 2-year survival of persons with advanced dementia (AD) in China. The study predicted the 2-year mortality of 115 persons with AD using the ADEPT score. In total, 115 persons with AD were included in the study. Of these persons, 48 died. The mean ADEPT score was 13.0. The AUROC for the prediction of the 2-year mortality rate using the ADEPT score was 0.62. The optimal threshold of the ADEPT score was 11.2, which had an AUROC of 0.63, specificity of 41.8, and sensitivity of 83.3. The ADEPT score based on a threshold of 11.2 may serve as a prognostic tool to determine the 2-year survival rate of persons with AD in Chongqing, China. However, further studies are needed to explore the nature of this relationship. [ABSTRACT FROM AUTHOR]

• CHIT1 regulates brain inflammation via HDAC3/NF-κB p65 pathway, contributing to improvement of cognitive impairment. • CHIT1 skews polarization from a pro-inflammatory environment toward an anti-inflammatory one. • CHIT1 has a potential therapeutic value in AD via modulation of inflammation. Chitotriosidase (CHIT1, chitinase 1) is increased in the cerebrospinal fluid and peripheral blood of Alzheimer's disease (AD) patients. Our previous study has shown that CHIT1 provides potential protection through microglial polarization and reduction of β-amyloid (Aβ) oligomers on rat models of AD. Histone deacetylase 3 (HDAC3) plays a significant role in the expression and regulation of proteins related to the pathophysiology of AD. In addition, nuclear factor-kappa B (NF-κB) signaling pathway activation in neurons is associated with the progression of AD. NF-κB activation is regulated by HDAC3 deacetylation. In the present study, we researched the role of CHIT1 in HDAC3/NF-κB signaling in D-galactose (D-gal) and aluminum-exposed rat model with cognitive impairments. Following CHIT1 treatment, we found that the protein and mRNA levels of HDAC3 and NF-κB were reduced, the expression level of IκBα increased, anti-inflammatory factors (Arg-1, IL-10, and CD206) were elevated while pro-inflammatory factors (TNF-a, iNOS, and IL-1β) were decreased in D-gal/aluminum-induced AD rats. These results indicate that CHIT1 can regulate brain inflammation via HDAC3/NF-κB p65 pathway, contributing to improvement of cognitive impairment. [ABSTRACT FROM AUTHOR]

Acute severe ulcerative colitis (ASUC) is a life-threatening condition that requires timely referral for therapy. Sarcopenia has been associated with clinical outcomes of inflammatory bowel disease (IBD). This study investigated the role of sarcopenia in predicting the clinical course of ASUC. This retrospective cohort study included ASUC patients with abdominal CT scans. Univariate and multivariable regression analyses were performed to identify a practical predictive index for the clinical course of ASUC. Of 233 included patients, 151 had intravenous corticosteroid (IVS) failure, among whom 32 received surgery without medical rescue therapy. Fifty patients underwent colectomy after medical rescue therapy failure. Of these 82 surgical patients, 42 suffered postoperative complications. Multivariable regression analysis showed that sarcopenia remained an independent risk factor for IVS failure (OR=2.969; 95% CI, 1.547–5.701; p = 0.001), colectomy after medical rescue therapy failure (OR=3.411; 95% CI, 1.147–10.141; p = 0.027), and postoperative complications after colectomy (OR=4.157; 95% CI, 1.364–12.667; p = 0.012). During follow-up, patients with colectomy after first-line treatment had a lower comprehensive complication index and better health-related quality of life. Sarcopenia is useful in predicting the clinical course and postoperative outcomes of ASUC. [ABSTRACT FROM AUTHOR]

Highlights • Chitotriosidase (CHIT1) treatment alone had no impact on TGFβ-Smad signaling and uptake of β-amyloid (Aβ) in N9 microglia. • CHIT1 enhanced TGFβ1-induced expression of TβRI and activation of Smad signaling in N9 microglia. • CHIT1 enhanced TGFβ1-induced phagocytosis of Aβ in N9 microglia, which was blocked by pretreatment with a TβRI inhibitor. Abstract TGFβ-Smad signaling is involved in the modulation of β-amyloid (Aβ) clearance in microglia. This signaling is impaired in the brain of Alzheimer's disease (AD). Chitotriosidase (CHIT1) is elevated in the cerebrospinal fluid and peripheral blood of AD patients, and has been reported to augment TGFβ signaling in fibroblast and T cells. In this study, we investigated the role of CHIT1 in TGFβ-Smad signaling and Aβ phagocytosis in N9 microglia. We found that CHIT1 significantly enhanced TGFβ1-induced expression of TβRI (TGFβ receptor I) and activation of Smad signaling. CHIT1 did not affect Aβ uptake in microglia by itself, but did enhance TGFβ1-induced phagocytosis of Aβ, which was blocked by pretreatment with SB431542 (TβRI inhibitor). These results indicate that CHIT1 may play a protective role in Aβ clearance by enhancing TGFβ signaling in microglia. [ABSTRACT FROM AUTHOR]

Chitinase activity is increased in Alzheimer’s disease (AD). However, the role of chitinase1 in AD is unknown. We investigated the effects of chitinase1 on Alzheimer’s pathology and microglia function. Artificial chitinase1 and chitinase inhibitor (chitinase-IN-2) were used to determine the effects of chitinase1 on inflammatory factors and β-amyloid (Aβ) oligomers deposition in D-galactose/AlCl 3 -induced rat model with cognitive impairments. Aβ-treated N9 microglia cells were analyzed to further verify whether the changes in inflammatory factors following chitinase1 treatment were associated with microglia alternative activation. Our data displayed that the activity of chitinase1 was both improved in D-galactose/AlCl 3 -injected rats and Aβ-pretreated microglia. Moreover, there was an improvement in cognitive function in chitinase1-treated AD rats. Furthermore, anti-inflammation factors (Arginase 1, Arg-1, mannose receptor type C 1, MRC1/CD206) were increased and pro-inflammation factors (tumor necrosis factor alpha, TNFα, interleukin 1 beta, IL-1β) were decreased in D-galactose/AlCl 3 -induced AD rats with chitinase1 treatment. A higher level of M2 markers (Arg-1, MRC1/CD206) and a lower level of classic M1 markers (TNFa, IL-1β) were obtained in Aβ-pretreated N9 cells with chitinase1, suggesting that chitinase1 polarized the microglia into an anti-AD M2 phenotype. We also detected that chitnase1 could weaken the deposition of Aβ oligomers in the brain of D-galactose/ AlCl 3 - induced AD rats. In conclusion, Chitinase1 might exert protective effects against AD by polarizing microglia to an M2 phenotype and resisting Aβ oligomer deposition. [ABSTRACT FROM AUTHOR]

National civilized city selection activity organized by Chinese government is a kind of policy taking both environmental protection and economic growth into consideration. It is of great importance to high-quality economic growth of China. This paper mainly selects data of 280 at and above prefecture-level cities in China from 2005 to 2016 and combines multi-stage difference-in-differences model to test the impacts of national civilized city selection on green total factor productivity (GTFP). The empirical results show that national civilized city selection activity can significantly promote the GTFP and have strong robustness. And the positive influence can be achieved through the mechanism of city innovation. In addition, heterogenous effects exist under different city administrative hierarchies and different regions. Finally, conclusions of this research for one thing provide empirical evidences for mutual development of economic growth and environmental protection; for another thing, this paper enriches policy evaluation researches of national civilized city by including environmental factors in total factor productivity calculation. • City carbon emission is used in evaluating green total factor productivity (GTFP). • National civilized city selection has positive impact on GTFP and is robust. • City innovation plays a vital role in the process of the policy promotes GTFP. • The policy effect varies in different city administrative hierarchies and regions. [ABSTRACT FROM AUTHOR]

Public environmental awareness (PEA) is critical to the implementation of environmental policies by governments and product strategies by companies, however, there is less literature discussing its drivers. Environmental information disclosure (EID), as a bottom-up environmental policy, promotes public environmental management. This paper takes the Pollution Information Transparency Index (PITI) as a proxy for the degree of EID and discusses its impact on PEA. Using the PITI of 113 cities and the Baidu index-based PEA for 30 provinces from 2010 to 2019, we find a significant increase in PEA with the widening of EID, and the impacts of EID get larger as the quantile increases. Moreover, the effects of EID on PEA are amplified in areas with heavy pollution, high levels of green innovation, and stringent environmental governance capacities, but are diminished in areas with rampant corruption. The findings of this paper provide recommendations for optimizing EID implementation. • With the expansion of EID, PEA has increased significantly. • The impacts of EID on PEA are amplified in areas with high pollution, green innovation, and strict governance capacities. • The impacts of EID on PEA are diminished in areas with rampant corruption. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Our previous study using proteomic analysis showed that superoxide dismutase 1 (SOD1) was significantly decreased in cerebrospinal fluid (CSF) of patients with epilepsy. However, the relevance of CSF-SOD1 alterations for the pathophysiology of epilepsy is currently unknown. The present study was intended to add to our understanding of this issue by measuring SOD1 levels in the CSF of patients with resistant epilepsy and non-resistant epilepsy. Methods: A total of 52 patients with epilepsy were recruited. 29 were non-resistant, 23 drug-resistant. 20 individuals with no evidence of any neurological diseases were used as control. The concentration of CSF and serum SOD1 was measured by enzyme-linked immunosorbent assay. Results: The concentration of CSF-SOD1 was decreased in both the drug-resistant (0.13±0.12ng/ml) and the non-resistant epilepsy subgroups (0.29±0.23ng/ml) compared to the control group (0.40±0.35ng/ml). SOD1 was significantly lower in the drug-resistant than the non-resistant epilepsy subgroup (P <0.05). Conclusion: SOD1 levels are decreased in the CSF of patients with epilepsy, especially of patients with intractable epilepsy. Low CSF-SOD1 levels may be a predictor of antiepileptic drug resistance in patients with epilepsy. [Copyright &y& Elsevier]

Abstract: Ti(IV)-functionalized derivatives of mesostructured HMS and MCM-41 silica with 3D wormhole and 1D hexagonal framework structures, respectively, were examined as catalysts for the oxidation of 4-tert-butyltoluene to 4-tert-butylbenzaldehyde using tert-butylhydroperoxide (TBHP) and aqueous hydrogen peroxide as oxidizing agents in acetonitrile solution. In an effort to achieve optimal site-isolation of reactive Ti(IV) centers, functionalization was carried out through the grafting of titanocene dichloride to the framework walls of the pre-assembled mesostructures, followed by calcination. Clear evidence for the undesirable clustering of Ti(IV) centers with increasing Ti(IV) loading was obtained by UV–Vis spectroscopy. Thus, the Ti(IV)-loading in the silica framework was limited to values below 8mol%. Maximal 23.6% and 21.8% conversions of 4-tert-butyltoluene to 4-tert-butylbenzaldehyde with >99% selectivity were observed for 4.8% Ti-HMS and 4.8% Ti-MCM-41 catalysts using TBHP as the oxidant. Substantially lower conversions were obtained with H2O2 as the oxidant due to clustering of Ti(IV) centers under reaction conditions and the catalyzed disproportionation of H2O2 by those clusters. A 2.0% Ti-HMS derivative prepared by direct assembly from tetraethylorthosilicate and tetraisopropylorthotitanate, denoted Ti-HMS(DS), was less active than Ti(IV)-functionalized mesostructures prepared by post-assembly grafting reaction with titanocene dichloride. Direct assembly places too much Ti(IV) at inaccessible positions within the framework walls, whereas grafting ensures optimal access to site-isolated Ti(IV) sites at the pore surfaces. [Copyright &y& Elsevier]

2,3,5,4′-Tetrahydroxystilbene-2-O-β- d -glucoside (TSG) is the key bioactive ingredient extracted from Polygonum multiflorum Thumb. Pharmacological studies suggest that it exerts numerous biological effects, including anti-oxidant, anti-aging, and anti-inflammation. This study aimed at investigating the effect of TSG on diethylnitrosamine (DEN)-induced acute hepatotoxicity and DNA damage. Fifty male C57BL/6 mice were randomly divided into 5 groups (n = 10 each): control, DEN, DEN+TSG (low), DEN+TSG (high) and TSG (high) groups. DEN (100 mg/kg) was injected intraperitoneally (i.p.) alone or with TSG (30 or 60 mg/kg, i.p.) for 5 consecutive days. TSG inhibited liver injury and inflammatory cell infiltration in DEN-treated mice. It also attenuated DEN-induced accumulation of reactive oxygen species (ROS), proinflammatory cytokines, and DNA damage. Moreover, TSG promoted the expression of nuclear erythroid 2-related factor 2 (Nrf2) target antioxidant genes by enhancing Nrf2 protein phosphorylation and nuclear translocation. As major phase I detoxification enzymes, cytochrome P450 family 2 subfamily E member 1 (CYP2E1) and cytochrome P450 1 subfamily A member 1 (CYP1A1) are responsible for the metabolic activation of DEN. We found that TSG administration inhibited CYP2E1 and CYP1A1 induction in DEN-treated mice. These results indicate that TSG can alleviate DEN-induced acute hepatotoxicity by modulating the Nrf2-related antioxidant system and metabolic activation of DEN. Therefore, TSG might be a promising medication for DEN-induced liver injury treatment. Unlabelled Image [ABSTRACT FROM AUTHOR]

Background Chronic itch is a highly debilitating symptom that underlies many medical disorders with no universally effective treatments. Although unique neuronal signaling cascades in the sensory ganglia and spinal cord have been shown to critically promote the pathogenesis of chronic itch, the role of skin-associated cells remains poorly understood. Objective We sought to examine the cutaneous mechanisms underlying transient receptor potential vanilloid 4 (TRPV4)–mediated allergic and nonallergic chronic itch. Methods Expression of TRPV4 in chronic itch and healthy control skin preparations was examined by using real-time RT-PCR. Trpv4 eGFP mice were used to study the expression and function of TRPV4 in the skin by means of immunofluorescence staining, flow cytometry, calcium imaging, and patch-clamp recordings. Genetic and pharmacologic approaches were used to examine the role and underlying mechanisms of TRPV4 in mouse models of dry skin–associated chronic itch and spontaneous scratching associated with squaric acid dibutylester–induced allergic contact dermatitis. Results TRPV4 is selectively expressed by dermal macrophages and epidermal keratinocytes in mice. Lineage-specific deletion of TRPV4 in macrophages and keratinocytes reduces allergic and nonallergic chronic itch in mice, respectively. Importantly, TRPV4 expression is significantly increased in skin biopsy specimens from patients with chronic idiopathic pruritus in comparison with skin from healthy control subjects. Moreover, TRPV4-dependent chronic itch requires 5-hydroxytryptamine (5-HT) signaling secondary to activation of distinct 5-HT receptors in mice with allergic and those with nonallergic chronic itch conditions. Conclusion Our study reveals previously unrecognized mechanisms by which TRPV4-expressing epithelial and immune cells in the skin critically and dynamically mediate chronic itch and unravels novel targets for therapeutics in the setting of chronic itch. [ABSTRACT FROM AUTHOR]

Irisin is an exercise-induced myokine that alleviates inflammation and obesity. The induction of anti-inflammatory (M2) macrophage is facilitated for treatment of sepsis and associated lung damage. However, whether irisin drives macrophage M2 polarization remains unclear. Here, we found that irisin induced-macrophage anti-inflammatory differentiation in vivo using an LPS-induced septic mice model and in vitro using RAW64.7 cells and bone marrow-derived macrophages (BMDMs). Irisin also promoted the expression, phosphorylation, and nuclear translocation of peroxisome proliferator-activated receptor gamma (PPAR-γ) and nuclear factor-erythroid 2-related factor 2 (Nrf2). Inhibition or knockdown of PPAR-γ and Nrf2 abolished irisin-induced accumulation of M2 macrophage markers, such as interleukin (IL)-10 and Arginase 1. Furthermore, dual-luciferase reporter and chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) assays confirmed that STAT6 boosts PPAR-γ and Nrf2 transcription by binding to their DNA promoters in irisin-stimulated macrophages. In contrast, STAT6 shRNA blocked the irisin-induced activation of Pparγ, Nrf2 , and related downstream genes. Moreover, the interaction of irisin with its ligand integrin αVβ5 remarkably promoted Janus kinase 2 (JAK2) phosphorylation, while inhibition or knockdown of integrin αVβ5 and JAK2 attenuated the activation of STAT6, PPAR-γ, and Nrf2 signaling. Interestingly, co-immunoprecipitation (Co-IP) assay also revealed that the binding between JAK2 and integrin αVβ5 is critical for irisin-induced macrophage anti-inflammatory differentiation by enhancing the activation of the JAK2-STAT6 pathway. In conclusion, irisin boosted M2 macrophage differentiation by inducing JAK2-STAT6-dependent transcriptional activation of the PPAR-γ-related anti-inflammatory system and Nrf2-related antioxidant genes. The findings of this study suggest that the administration of irisin is a novel and promising therapeutic strategy for infectious and inflammatory diseases. [Display omitted] • Irisin drives anti-inflammatory macrophage differentiation. • STAT6 directly promotes the transcription of PPAR-γ and Nrf2 in irisin-treated macrophages. • The binding of JAK2 and irisin membrane ligand integrin αVβ5 enhances the activation of JAK2-STAT6 signaling pathway. • Irisin is a novel therapeutic strategy for infectious, inflammatory diseases. [ABSTRACT FROM AUTHOR]

Frailty, cognitive decline, and depression are common syndromes among the elderly and are closely interconnected. However, it is still unclear whether the impact of frailty on depression depends on the role of cognitive decline. We conducted the Mendelian randomization (MR) analysis based on the instrumental variables (IVs) from the genome-wide association study (GWAS) databases, and we also performed a cross-sectional study consisting of 1362 older adults aged ≥65 for validation. The results of the multivariable MR analysis showed that frailty significantly increased the risk of depression, even after controlling for the influence of cognitive performance. Conversely, after controlling for frailty, the effect of cognitive performance on depression risk was noticeably reduced. In the cross-sectional study, frailty mediated 24.04 % of the relationship between cognition and depression, and cognition mediated 7.63 % of the relationship between frailty and depression. We provide evidence that frailty could increase depression risk independently of cognitive decline. Further research with a larger sample size is necessary. • Frailty as a more aggressive player for depression risk than cognitive impairment • Independent role of frailty in aggravating depression risk • Mendelian causality between frailty and depression validated by real-world cross-sectional study • Imbalanced co-operation between frailty and cognition in augmenting the prevalence of depression [ABSTRACT FROM AUTHOR]

Abstract: Purpose: The transforming growth factor β (TGF-β) signaling pathway is involved in the epileptogenesis. Sorting Nexin 25 (SNX25) has been recently proposed to modulate TGF-β signaling through endosomal sorting of TGF-β receptors for lysosomal degradation. The aim of the present study was to determine the expression pattern of SNX25 in brains of epilepsy patients and in animal model of epilepsy. Methods: We investigated the expression of SNX25 in the brain tissues of patients with temporal lobe epilepsy (TLE) and in the pilocarpine-induced rat model of epilepsy using western blotting, real-time quantitative RT-PCR, and double-label immunofluorescence. Results: The expression of SNX25 was significantly increased in TLE patients in comparison to controls (0.21±0.07 vs. 0.11±0.03, P<0.05). In the lithium-pilocarpine induced epileptic rats, significant elevation of SNX25 levels was detected in the chronic phase, while no SNX25 alteration occurred in the acute and latent phases. Moreover, SNX25 localized to astrocytes and neurons, in both human samples and animal models. Conclusion: Our results indicate that upregulation of SNX25 might be involved in the development of temporal lobe epilepsy. [Copyright &y& Elsevier]

• Observation of the clinical efficacy in three real-world DAAs cohorts in China. • Previous studies focused on changes of HCV genomes under selective pressure in relapsed patients are limited. • Next-generation sequencing was used as the detection method to cover near full-length genome of HCV (27 gene fragments for 1b and 3b, 26 gene fragments for 6a). • Resistance-associated variants, viral quasispecies diversity and selection analysis were analyzed in this study. Currently, direct-acting antiviral drugs (DAAs) are widely used as therapeutic methods for hepatitis C virus (HCV)-positive patients, however, patients may experience treatment failure, and the dynamic changes of HCV genomes in these patients are unknown. In this study, three real-world DAAs cohorts were enrolled to observe clinical efficacy. In addition, serum samples from treatment failure patients at baseline and relapse were used to analyze changes of the HCV genomes at near full-length genome level, including resistance-associated variants (RAVs), viral quasispecies diversity and selection analysis. Next-generation sequencing was used as the detection method. The overall sustained virological response at 12 w after the end of treatment was achieved in 91.9% (57/62) of HCV patients, and 3 paired samples obtained from relapsed patients. All the 3 patients harbored baseline NS5A RAVs, the frequency of NS5A RAVs increased in 2 patients and a new NS5A RAV emerged in 1 patient at relapse, and almost all the viral strains existed with NS5A RAVs at relapse. The results of the viral quasispecies diversity analysis revealed that viral quasispecies diversity decreased at relapse compared to baseline, and the results of selection analysis indicated that the virus population experienced a bottleneck phenomenon, recent selective sweep and population expansion or was under purification selection after DAAs treatment. This study indicated that the clinical efficacy was excellent in real-world DAAs cohorts, and the viral strains existed at relapse were selective by DAAs therapy. [ABSTRACT FROM AUTHOR]

The effects of treatment by ultrasound (US), inoculation of Pediococcus acidilactici BP2 strain (BP), and their combination (US-BP) on the quality characteristics of beef jerky were investigated during fermentation for 6 days. Moisture contents and water activity were highest after the US and US-BP treatments (P < 0.05). These effects were attributed to the decreased moisture mobility in beef jerky during ultrasonication. Meanwhile, samples treated with US and US-BP displayed more broken muscle fibers and larger gaps and cavities between the adjacent muscle bundles, resulting in lower shear force values compared to the other samples (P < 0.05), which indicated that the US and US-BP treatments improved the tenderness of beef jerky. Moreover, treatment with BP promoted the flavor development of beef jerky. The US-BP treatment improved the sensory attributes of beef jerky. In conclusion, US-BP is a promising strategy to improve the quality of beef jerky. • Ultrasound treatment decreased moisture mobility and shear force of beef jerky. • Ultrasound treatment broke muscle fibers and increased the tenderness of beef jerky. • Inoculation of P. acidilactici BP2 enhanced the flavor development of beef jerky. • Combined ultrasound and starter culture inoculation improved the beef jerky quality. [ABSTRACT FROM AUTHOR]

Background: The iatrogenic injuries to the lumbar nerves during the fixation the sacroiliac (SI) joint fractures with anterior plates were often reported. No specific method had been reported to avoid it. This study was done to find a safer way of placing the anterior plates and screws for treating the sacroiliac (SI) joint fracture and/or dislocation.Methods: The research was performed using 8 male and 7 female normal corpse pelvic specimens preserved by 10% formalin solution. Try by measuring the horizontal distance from L4, L5 nerve roots to the sacroiliac joint and perpendicular distance from L4, L5 nerve roots to the ala sacralis, the length of L4, L5 nerve roots from intervertebral foramen to the edge of true pelvis, the diameter of L4, L5 nerve roots. The angles between the sacroiliac joint and sagittal plane were measured on the CT images.Results: The horizontal distance between the lateral side of the anterior branches of L4, L5 nerve roots and the sacroiliac joint decreased gradually from the top to the bottom. The widest distances for L4,5 were 2.1 cm (range, 1.74-2.40) and 2.7 cm (range, 2.34-3.02 cm), respectively. The smallest distances for L4, 5 were 1.2 cm (range, 0.82-1.48 cm) and 1.5 cm (range, 1.08-1.74 cm), respectively. On CT images, the angle between the sacroiliac joint and sagittal plane was about 30°.Conclusions: If we use two anterior plates to fix the sacroiliac joint, It is recommended to place one plate on the superior one third part of the joint, with exposing medially no more than 2.5 cm and the other in the middle one third part of the joint, with elevating periosteum medially no more than 1.5 cm. The screws in the sacrum are advised to incline medially about 30° directing to the true pelvis. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder that is closely associated with insulin resistance and type 2 diabetes. Previous studies have suggested that hepatocyte nuclear factor 1b (HNF1b) ameliorates insulin resistance. However, the role of HNF1b in the regulation of lipid metabolism and hepatic steatosis remains poorly understood. We found that HNF1b expression was decreased in steatotic livers. We injected mice with lentivirus (LV) expressing HNF1b shRNA to generate mice with hepatic knockdown of HNF1b. We also injected high fat (HF) diet-induced obese and db/db diabetic mice with LV expressing HNF1b to overexpress HNF1b. Knockdown of HNF1b increased hepatic lipid contents and induced insulin resistance in mice and in hepatocytes. Knockdown of HNF1b worsened HF diet-induced increases in hepatic lipid contents, liver injury and insulin resistance in mice and PA-induced lipid accumulation and impaired insulin signaling in hepatocytes. Moreover, overexpression of HNF1b alleviated HF diet-induced increases in hepatic lipid content and insulin resistance in mice. Knockdown of HNF1b increased expression of genes associated with lipogenensis and endoplasmic reticulum (ER) stress. DPP4 and NOX1 expression was increased by knockdown of HNF1b and HNF1b directly bound with the promoters of DPP4 and NOX1. Overexpression of DPP4 or NOX1 was associated with an increase in lipid droplets in hepatocytes and decreased expression of DPP4 or NOX1 suppressed the effects of knockdown of HNF1b knockdown on triglyceride (TG) formation and insulin signaling. Knockdown of HNF1b increased superoxide level and decreased glutathione content, which was inhibited by downregulation of DPP4 and NOX1. N-acetylcysteine (NAC) suppressed HNF1b knockdown-induced ER stress, TG formation and insulin resistance. Palmitic acid (PA) decreased HNF1b expression which was inhibited by NAC. Taken together, these studies demonstrate that HNF1b plays an essential role in controlling hepatic TG homeostasis and insulin sensitivity by regulating DPP4/NOX1mediated generation of superoxide. [ABSTRACT FROM AUTHOR]

Neural stem cells (NSCs) migration is essential for neurogenesis and neuroregeneration after brain injury. Nestin, a widely used marker of NSCs, is expressed abundantly in several cancers, where it may correlate with tumor migration and invasion. However, it is not yet known whether nestin participates in NSC migration. Here, we show that nestin down-regulation significantly inhibits the migration and contraction of murine neural stem cells, but does not obviously influence the proliferation, filamentous actin (F-actin) content, distribution or focal adhesion assembly of these cells. Mechanistically, nestin knockdown was found to affect the phosphorylation state of myosin regulatory light chain (MRLC) and regulate the activity of myosin light chain kinase (MLCK). Co-immunoprecipitation experiments showed that it interacts with MLCK and MRLC. Together, our results indicate that nestin may increase NSC motility via elevating MLCK activity through direct binding and provide new insight into the roles of nestin in NSC migration and repair. [ABSTRACT FROM AUTHOR]

Objective: To reveal the relations between neuropsychiatric symptoms (NPS), stages of cognitive impairment, sex, and daily function in patients with mild cognitive impairment (MCI) and dementia due to Alzheimer's disease (AD).Methods: A cross-sectional study was conducted from 2014 to 2021 on 1154 patients. Cognitive function, disease severity, NPS, and daily function were evaluated by Mini-mental State Examination, Clinical Dementia Rating Scale, Neuropsychiatric Inventory, and Activities of Daily Living (ADL) respectively. Multivariate logistic regression and linear regression were used to explore the correlations between NPS, disease stage, sex and ADL.Results: Affective disturbance displayed the highest prevalence from MCI (52.7%) to severe dementia due to AD (98.2%). Multivariate logistic regression revealed that aberrant motor behavior displayed higher prevalence between groups from MCI to severe dementia due to AD (OR = 4.710, P < 0.001; OR = 3.141, P < 0.001; OR = 2.722, P = 0.002, respectively). In patients with dementia due to AD, hallucination and depression were more prevalent in female (OR = 1.730, P = 0.001; OR = 2.376, P < 0.001, respectively) while male presented higher prevalence in apathy (OR = 0.608, P = 0.002). Linear regression analysis showed that delusion and sleep disturbance were significantly associated with basic ADL across all dementia due to AD stages (delusion: mild: β = 0.113, P = 0.015; moderate: β = 0.159, P = 0.019; severe: β = 0.317, P = 0.018; sleep disturbance: mild: β = 0.164, P < 0.001; moderate: β = 0.167, P = 0.013; severe: β = 0.308, P = 0.025) while anxiety was correlated with instrumental ADL from MCI to moderate dementia due to AD (MCI: β = 0.119, P = 0.006; mild: β = 0.149, P < 0.001; moderate: β = 0.130, P = 0.042).Conclusion: Different subitems of NPS are strongly correlated with sex, stage of cognitive impairment, and ADL. [ABSTRACT FROM AUTHOR]

Alcoholic liver disease (ALD) has caused a serious burden on public and personal health in crowd with ethanol abuse. The effects of insulin resistance (IR) on ALD and the mechanisms underlying these responses are still not well understood. In this study, we investigated the changes of liver injury, inflammation, apoptosis, mitochondrial dysfunction and CYP2E1 changes in liver of mice exposed to ethanol with IR or not. We found IR increased the sensitivity of liver injury in mice exposed to ethanol, manifested as the increase serum activities of AST and ALT, the accumulation of triglycerides, the deterioration of liver pathology and increase of inflammatory factors. IR also exacerbated apoptosis and mitochondrial dysfunction in liver of mice exposed to ethanol. The increase of oxidative stress and the decrease of antioxidant defense ability might be responsible for the sensitizing effects of IR on ethanol-induced liver injury, supported by the increase of MDA levels and the decline of GSH/GSSG, the inactivation of antioxidant enzymes SOD, GR through the inhibition of Nrf-2 pathway. The activation of CYP2E1 might be also involved in the sensitizing effects of IR on ethanol induced liver injury in mice. These results demonstrated that IR exhibited a significant pro-oxidative and pro-apoptosis effects to aggravate alcoholic liver injury. Our study helped us to better understand the sensitive role of IR on ALD and suggested that alcohol intake may be more harmful for people with IR. [Display omitted] • Insulin resistance (IR) increased the sensitivity of liver injury and inflammation in ALD. • IR exacerbated mitochondrial dysfunction and apoptosis in liver of mice exposed to ethanol. • The increase of oxidative stress and the decrease of antioxidant defense ability might be responsible for the sensitizing effects of IR on ALD. • The activation of CYP2E1 might be involved in the sensitizing effects of IR on ALD. [ABSTRACT FROM AUTHOR]

Obesity has become a worldwide public health problem, which is mainly determined by excess energy intake and adipose tissue expansion. Adipose tissue expansion can occur through hyperplasia (adipocyte differentiation) or hypertrophy. Retinoic acid was shown to inhibit adipocyte differentiation. However, the molecular mechanism is unclear. In the study, we found that all-trans-retinoic acid (ATRA) inhibited 3T3-L1 adipocyte differentiation. We did not observe significant apoptosis in differentiated adipocytes treated by ATRA. ATRA increased ROS generation and disturbed redox balance. However, antioxidant treatment did not ameliorate the reduction of lipid accumulation induced by ATRA, indicating that ROS generation was not involved in ATRA-inhibited adipocyte differentiation. ATRA reduced C/EBPα, PPARγ and its target gene expression. In the presence of ATRA, retinoic acid receptor (RAR) α/γ expression was increased. Inhibition of RARγ, but not RARα, blocked ATRA-induced reduction of PPARγ2 expression. ATRA induced a profound interaction between RARγ and C-Fos protein, reflected by Co-IP results. C-Fos was found to exhibit a differentiation-dependent DNA binding activity to PPARγ2 promoter. RARγ inhibitor significantly suppressed ATRA-inhibited DNA binding activity of C-Fos to PPARγ2 promoter, indicating that downregulation of C-Fos activity mediated activation of RARγ-exerted reduction of PPARγ2 expression and thus inhibition of adipocyte differentiation induced by ATRA. Taken together, these data demonstrates that RARγ-C-Fos-PPARγ2 signaling rather than ROS generation is critical for ATRA-inhibited adipocyte differentiation. [ABSTRACT FROM AUTHOR]

Abstract: Human mesenchymal stem cells hold promise as gene therapy vectors for delivery of various genes to solid tumors for either therapeutic or tumor-tracing purposes. However, whether Mesenchymal stem cells support or inhibit tumor growth remains unknown. Herein, we first observed that mesenchymal stem cells primed with IFN-γ selectively induced the death of tumor cell lines, but not normal cells. We further identified that IFN-γ-primed mesenchymal stem cells expressed tumor necrosis factor-related apoptosis-inducing ligand. Tumor-suppressive effect of IFN-γ-primed mesenchymal stem cells could be blocked by activity neutralization or expression reduction of tumor necrosis factor-related apoptosis-inducing ligand. Moreover, mesenchymal stem cells mediated apoptosis of tumor cells by activating caspase-3 in such cells, via a mechanism involving tumor necrosis factor-related apoptosis-inducing ligand. However, when IFN-γ-primed or non-primed mesenchymal stem cells were co-injected into nude mice along with H460 cells, tumor growth was much faster than that of the group receiving only tumor cells (p <0.01) because of the promoting vascularization effect of mesenchymal stem cells, although IFN-γ-primed mesenchymal stem cells also exerted a certain degree of tumor-suppressive effect compared with non-primed cells (2.79±0.9g versus 2.03±0.6g). Collectively, our findings show that IFN-γ-primed human mesenchymal stem cells could induce cancer cell apoptosis via TRAIL-mediated pathway. In addition, our data afford a novel explanation of the opposing effects of hMSCs presence on tumor growth in vitro and in vivo. Thus, more attention needs to be paid when seeking to exploit mesenchymal stem cells as a therapeutic option under the condition of malignant tumor. [Copyright &y& Elsevier]

Abstract: A novel biomimetic composite scaffold Bioglass-Collagen-Phosphatidylserine (BG-COL-PS) was fabricated with a freeze-drying technique. The macrostructure and morphology as well as mechanical strength of the scaffolds were characterized. Scanning electronic microscopy (SEM) showed that the BG-COL-PS scaffolds exhibited interconnected porous structures with pore sizes of several microns up to about 300 μm. The scaffolds have a porosity of 75.40% and the corresponding compressive strength of 1.5469 Mpa. Rat mesenchymal stem cells (rMSCs) were seeded on BG-COL-PS or BG-COL scaffolds and cultured for 21 days in vitro. Based on the results of SEM, dsDNA content, alkaline phosphatase (ALP) activity, osteogenic gene expression analysis and alizarin red staining, the responses of MSCs to the scaffold exhibited a higher degree of attachment, growth as well as osteogenic differentiation than those on BG-COL scaffolds in vitro. To investigate the in vivo biocompatibility and osteogenesis of the composite scaffolds, both pure BG-COL-PS scaffolds and MSC/scaffold constructs were implanted in rat femurs defects for 6 weeks and studied histologically and radiographically. The in vivo results showed that BG-COL-PS composite scaffolds exhibited good biocompatibility and extensive osteoconductivity with host bone. Moreover, the BG-COL-PS/MSC constructs dramatically enhanced the efficiency of new bone formation than pure BG-COL-PS scaffolds or BG-COL/MSC constructs. All these results demonstrate the usefulness of PS composited BG-COL-PS scaffolds for inducing enhanced bone formation. The BG-COL-PS scaffolds fulfill the basic requirements of bone tissue engineering scaffold and have the potential to be applied in orthopedic and reconstructive surgery. [ABSTRACT FROM AUTHOR]

Abstract: We report an improved absorbent material for NO x , a major component of acid rain and other environmentally hazardous chemicals. This new material is based on the hydrotalcite-like compounds and incorporating Mg and Zn markedly enhances the capacity of adsorbing NO x . Ni/Al, Mg/Ni/Al, and Zn/Mg/Ni/Al hydrotalcite-like compounds were synthesized by coprecipitation, characterized by X-ray diffraction (XRD), ICP, infrared (IR), and scanning electron microscopy (SEM) and tested for the performance in adsorption of NO x on derived mixed oxides. The prepared adsorbents give better performance than the conventional activated carbons. The adsorption capacity for NO x is highly dependent on the composition of adsorbent materials. The capacity is highest for Zn1Mg1Ni1Al1 at 2300mg/g, with 73% efficiency. The physical and structural properties of the materials before and after NO x adsorption were investigated to gain a better understanding of the underlying mechanism. IR d-spacing and SEM measurements indicate that physisorption and chemisorption have occurred cooperatively. Adsorption of NO x has led to the reformation of layered double structure by the resultant nitrates and nitrites around the oxide sites between the positively charged layers of the hydrotalcite. As a consequence, it catalyses more and more NO x to be absorbed. Other possible mechanisms are also discussed. [Copyright &y& Elsevier]

Silent information regulator 1 (SIRT1) is a NAD+-dependent protein-modifying enzyme involved in regulating gene expression, DNA damage repair, cell metabolism, and mitochondrial functions. Given that it acts as both a tumor promoter and suppressor, the complex mechanisms underlying SIRT1 signaling in cancer remain controversial. Epithelial-to-mesenchymal transition (EMT) plays a key role in the progression of carcinogenesis and tumors metastasis. Studies have shown that mitochondrial defects are critical in EMT process, and SIRT1 is found to regulate the generation and energy metabolism of mitochondria. Here, we elucidate a novel mechanism by which SIRT1 affects EMT in lung cancer cells via its regulation on mitochondria. SIRT1 signaling was detected in TGF-β1-induced EMT and was found to regulate mitochondria status, including mitochondrial biogenesis-related protein levels as detected by western blotting, mitochondrial structure observed by transmission electron microscopy, and respiratory functions analyzed by a respiration capacity assay. The effects of modulating SIRT1 expression on EMT and migration of lung cancer cells or normal cells were evaluated by in vitro and in vivo models. We found that the regulation of SIRT1 signaling on the biogenesis or functions of mitochondria was critical to EMT. Overexpression of SIRT1 reduced EMT or metastasis potential of lung cancer cells by improving the quantity and quality of mitochondria, whereas silencing SIRT1 promote EMT in cancer cells, even in normal cells by disturbing mitochondria status. Consequently, SIRT1 is an attractive therapeutic target for reversing EMT or tumor metastasis. [Display omitted] • The regulation of SIRT1 signaling on the biogenesis or functions of mitochondria was critical to EMT. • Overexpression of SIRT1 reduced EMT or metastasis potential of lung cancer cells by improving mitochondria status. • Silencing SIRT1 promotes EMT or metastasis potential of lung cancer cells by disturbing mitochondria status. • SIRT1 is an attractive therapeutic target for its suppression on EMT. [ABSTRACT FROM AUTHOR]

Polychlorinated biphenyls (PCBs) exposure is closely associated with the prevalence of metabolic diseases, including fatty liver and dyslipidemia. Emerging literature suggests that disturbance of gut microbiota is related to PCB126-induced metabolic disorders. However, the causal role of dysbiosis in PCB126-induced fatty liver is still unknown. To clarify the role of the gut microbiome in the detoxification of PCB126 in intestine or PCB126-induced toxicity in liver, mice were administrated with drinking water containing antibiotics (ampicillin, vancomycin, neomycin, and metronidazole) or Inulin. We showed that PCB126 resulted in significant hepatic lipid accumulation, inflammation, and fibrosis. PCB126, Antibiotics, and Inulin significantly affected the structure and shifted community membership of gut microbiome. 7 KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways at level 2 and 39 KEGG pathways at level 3 were significantly affected. Antibiotics alleviated PCB126-induced fibrosis in the liver but increased inflammation. Inulin treatment ameliorated both inflammation and fibrosis in the liver of PCB126-treated mice. Neither Antibiotics nor Inulin had significant effect on PCB126-induced hepatic steatosis. The more specific intervention of gut microbiota is needed to alleviate PCB126-induced fatty liver. These data demonstrate that homeostasis of gut microbiota is critical for the defense against PCB126 toxicity and dysbiosis plays a fundamental role in the development of inflammation and fibrosis in liver of PCB126-treated mice. Unlabelled Image • PCB126 significantly induced dysbiosis and hepatic steatosis, inflammation and fibrosis. [ABSTRACT FROM AUTHOR]

Kaolinite, a natural, abundant, low cost, and eco-friendly material, has been widely used as filler, additives, adsorbent and coatings. In the study, kaolinite was evaluated for the performance of the hydrolysis of cellulose in water. The effects of mass ratio, reaction temperature, reaction time and water amount were investigated in a batch reactor. The fresh and regenerated catalysts were characterized by XRD, FT-IR and TG-DTG. The catalytic results showed that the highest TRS yield of 38.8% was obtained on the kaolinite at 200 °C with the mass ratio of catalyst to cellulose of 0.2 for 3 h. Moreover, kaolinite was a stable catalyst after regeneration and the yield of TRS decreased from 38.8% to 38.1% after five times reuse. Kaolinite contains abundant surface Al-OH groups, and the high TRS yield for kaolinite should be attributed to the H+ ions released from the surface OH groups. This work provides a promising strategy for efficient cellulose hydrolysis into fine chemicals by natural clay minerals. Unlabelled Image • Kaolinite is an efficient catalyst for the hydrolysis of cellulose in water. • Kaolinite presents a high regeneration stability. • Surface Al-OH groups are responsible for the cellulose hydrolysis. • H-bond between Al-OH and Si O weakens the O H bond in Al-OH groups. • H+ ions in Al-OH groups are responsible for the depolymerization of cellulose. [ABSTRACT FROM AUTHOR]

Cellulose is the most abundant form of biomass on earth, and is considered as an alternative for fuels and chemicals. The hydrolysis of cellulose to platform compounds, such as reducing sugars (RS), is one of the most important ways for the utilization of cellulose. In this study, the solid acid catalysts of SO 4 2−-ZrO 2 /montmorillonite (SZ-Mt) were prepared by coupling SO 4 2− with ZrO 2 and then introducing into the interlayer of Mt using the coprecipitation method. Meanwhile, the catalytic performance of the SZ-Mt catalysts for the hydrolysis of cellulose to RS in water was studied. The catalysts were characterized by XRD, FT-IR, BET, SEM(EDS), NH 3 -TPD and XPS. The catalytic results showed that the SZ-Mt composite calcined at 500 °C with the molar ratio of S/Zr of 0.3 showed the highest total reducing sugars yield of 30.1%. The characterization results revealed that the surface S O bonds of sulfated zirconium oxide could gradually change from O=S-OH groups (type I, -HSO 4) to O=S=O groups (type II, -S 2 O 7). It was concluded that the surface S-OH groups in type I were responsible for the hydrolysis of cellulose in the low molar ratio of S/Zr and the new S-OH bonds formed by breaking the S-O-S bonds in type II were contributed to the conversion of cellulose in the high molar ratio of S/Zr. Finally, the mechanism of cellulose hydrolysis on the SZ composites was suggested. Unlabelled Image • The SO 4 2−-ZrO 2 /montmorillonite composite was used for the hydrolysis of cellulose in water. • The surface S O bonds changed from O=S-OH to O=S=O groups with the increasing of S content. • Both O=S-OH and O=S=O groups were responsible for the hydrolysis of cellulose. • The hydrolysis mechanism on the solid catalyst was proposed. [ABSTRACT FROM AUTHOR]