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Abstract Macrophage‐mediated inflammatory responses including pyroptosis are involved in the pathogenesis of sepsis and acute lung injury (ALI), for which there are currently no effective therapeutic treatments. The natural product (+)‐Balasubramide is an eight‐membered lactam compound extracted from the leaves of the Sri Lanka plant Clausena Indica and has shown anti‐inflammatory activities, but its poor pharmacokinetic properties limit its further application for ALI. In this study, a compound (+)3C‐20 is discovered with improved both pharmacokinetic properties and anti‐inflammatory activity from a series of (+)‐Balasubramide derivatives. The compound (+)3C‐20 exhibits a markedly enhanced inhibitory effect against LPS‐induced expressions of pro‐inflammatory factors in mouse macrophages and human PBMCs from ALI patients and shows a preferable lung tissue distribution in mice. (+)3C‐20 remarkably attenuates LPS‐induced ALI through lung tissue‐specific anti‐inflammatory actions. Mechanistically, a chemical proteomics study shows that (+)3C‐20 directly binds to mitochondrial VDAC1 and inhibits VDAC1 oligomerization to block mtDNA release, further preventing NLRP3 inflammasome activation. These findings identify (+)3C‐20 as a novel VDAC1 inhibitor with promising therapeutic potential for ALI associated with inflammation.

Purpose: To explore the utility of high frequency oscillations (HFO) and long-range temporal correlations (LRTCs) in preoperative assessment of epilepsy. Methods: MEG ripples were detected in 59 drug-resistant epilepsy patients, comprising 5 with parietal lobe epilepsy (PLE), 21 with frontal lobe epilepsy (FLE), 14 with lateral temporal lobe epilepsy (LTLE), and 19 with mesial temporal lobe epilepsy (MTLE) to identify the epileptogenic zone (EZ). The results were compared with clinical MEG reports and resection area. Subsequently, LRTCs were quantified at the source-level by detrended fluctuation analysis (DFA) and life/waiting -time at 5 bands for 90 cerebral cortex regions. The brain regions with larger DFA exponents and standardized life-waiting biomarkers were compared with the resection results. Results: Compared to MEG sensor-level data, ripple sources were more frequently localized within the resection area. Moreover, source-level analysis revealed a higher proportion of DFA exponents and life-waiting biomarkers with relatively higher rankings, primarily distributed within the resection area (p

Abstract Given the inconsistent results on the prognostic significance of epicardial adipose tissue (EAT), the purpose of the present study was to investigate the association of EAT thickness and myocardial work by non-invasive left ventricular pressure-strain loop in people with suspected metabolic syndrome (MS). A total of 194 participants imaged with echocardiography were evaluated. In accordance with the median EAT thickness, MS patients fell into thin EAT group and thick EAT group. Conventional echocardiographic parameters, global longitudinal strain (GLS) and the global myocardial work parameters obtained by pressure-strain loop analysis, comprising the global work index (GWI), global work efficiency (GWE), global constructive work (GCW) and global wasted work (GWW) were compared between the two groups. In comparison with the thin EAT group, thick EAT group achieved significantly higher values in interventricular septal thickness, end-diastolic left ventricular posterior wall thickness, left ventricular mass index and GWW (p

ABSTRACT: Background: We aimed to comprehensively examine how the anatomic characteristics of asymptomatic third molars (As-M3s) affect distal pathologies of adjacent second molars (Ad-M2s). Materials and methods: Patients with at least 1 quadrant having intact As-M3s and first and second molars were enrolled. Distal pathologies of Ad-M2s, including caries, pocket depth of 4 mm or more (PD4+), and alveolar bone loss of 3 mm or more (ABL3+), were analysed based on As-M3 status (absent/impacted/nonimpacted). Especially within nonimpacted M3s (N-M3s), the effects of regions (maxillary vs mandibular) and dental intervals (narrow vs wide) on Ad-M2 pathologies were further compared. Results: A total of 248 patients with their 805 quadrants were finally included in this cross-sectional study. The impacted and nonimpacted As-M3s elevated the risk of any distal pathology (caries, PD4+, or ABL3+) of Ad-M2s vs M3 absence with odds ratios (ORs) of 8.33 and 3.27, respectively. Within N-M3s, mandibular regions increased the odds of PD4+ (OR, 1.96); wide dental intervals increased the odds of ABL3+ (OR, 3.01). However, maxillary regions and narrow dental intervals contributed to more severe bone loss in Ad-M2s with ABL3+. Conclusions: The presence of As-M3 is a risk factor for Ad-M2 pathologies irrespective of impaction status. Within N-M3s, Ad-M2 pathologies are significantly influenced by anatomic characteristics such as regions and dental intervals.

Abstract Staphylococcus aureus (SA) is a major cause of sepsis, leading to acute lung injury (ALI) characterized by inflammation and oxidative stress. However, the role of the Nrf2/PHB2 pathway in SA‐induced ALI (SA‐ALI) remains unclear. In this study, serum samples were collected from SA‐sepsis patients, and a SA‐ALI mouse model was established by grouping WT and Nrf2−/− mice after 6 h of intraperitoneal injection. A cell model simulating SA‐ALI was developed using lipoteichoic acid (LTA) treatment. The results showed reduced serum Nrf2 levels in SA‐sepsis patients, negatively correlated with the severity of ALI. In SA‐ALI mice, downregulation of Nrf2 impaired mitochondrial function and exacerbated inflammation‐induced ALI. Moreover, PHB2 translocation from mitochondria to the cytoplasm was observed in SA‐ALI. The p‐Nrf2/total‐Nrf2 ratio increased in A549 cells with LTA concentration and treatment duration. Nrf2 overexpression in LTA‐treated A549 cells elevated PHB2 content on the inner mitochondrial membrane, preserving genomic integrity, reducing oxidative stress, and inhibiting excessive mitochondrial division. Bioinformatic analysis and dual‐luciferase reporter assay confirmed direct binding of Nrf2 to the PHB2 promoter, resulting in increased PHB2 expression. In conclusion, Nrf2 plays a role in alleviating SA‐ALI by directly regulating PHB2 transcription and maintaining mitochondrial function in lung cells.

A field experiment was carried out to evaluate the effects of drip fertigation combined with plant hedgerows on nitrogen and phosphorus runoff losses in intensive pear orchards in the Tai Lake Basin. Nitrogen and phosphorus runoff over a whole year were measured by using successional runoff water collection devices. The four experimental treatments were conventional fertilization (CK), drip fertigation (DF), conventional fertilization combined with plant hedgerows (C+H), and drip fertigation combined with plant hedgerows (D+H). The results from one year of continuous monitoring showed a significant positive correlation between precipitation and surface runoff discharge. Surface runoff discharge under the treatments without plant hedgerows totaled 15.86% of precipitation, while surface runoff discharge under the treatments with plant hedgerows totaled 12.82% of precipitation. Plant hedgerows reduced the number of runoff events and the amount of surface runoff. Precipitation is the main driving force for the loss of nitrogen and phosphorus in surface runoff, and fertilization is an important factor affecting the losses of nitrogen and phosphorus. In CK, approximately 7.36% of nitrogen and 2.63% of phosphorus from fertilization entered the surface water through runoff. Drip fertigation reduced the accumulation of nitrogen and phosphorus in the surface soil and lowered the runoff loss concentrations of total nitrogen (TN) and total phosphorus (TP). Drip fertigation combined with plant hedgerows significantly reduced the overall TN and TP losses by 45.38 and 36.81%, respectively, in comparison to the CK totals. Drip fertigation increased the vertical migration depth of nitrogen and phosphorus nutrients and reduced the accumulation of nitrogen and phosphorus in the surface soil, which increased the pear yield. The promotion of drip fertigation combined with plant hedgerows will greatly reduce the losses of nitrogen and phosphorus to runoff and maintain the high fruit yields in the intensive orchards of the Tai Lake Basin.

Microglia are resident immune cells in the central nervous system. During the pathogenesis of Alzheimer’s disease, stimulatory factors continuously act on the microglia causing abnormal activation and unbalanced phenotypic changes; these events have become a significant and promising area of research. In this review, we summarize the effects of microglial polarization and crosstalk with other cells in the central nervous system in the treatment of Alzheimer’s disease. Our literature search found that phenotypic changes occur continuously in Alzheimer’s disease and that microglia exhibit extensive crosstalk with astrocytes, oligodendrocytes, neurons, and penetrated peripheral innate immune cells via specific signaling pathways and cytokines. Collectively, unlike previous efforts to modulate microglial phenotypes at a single level, targeting the phenotypes of microglia and the crosstalk with other cells in the central nervous system may be more effective in reducing inflammation in the central nervous system in Alzheimer’s disease. This would establish a theoretical basis for reducing neuronal death from central nervous system inflammation and provide an appropriate environment to promote neuronal regeneration in the treatment of Alzheimer’s disease.

The retinal ganglion cells of the optic nerve have a limited capacity for self-repair after injury. Valproate is a histone deacetylase inhibitor and multitarget drug, which has been demonstrated to protect retinal neurons. In this study, we established rat models of optic nerve-crush injury and injected valproate into the vitreous cavity immediately after modeling. We evaluated changes in the ultrastructure morphology of the endoplasmic reticulum of retinal ganglion cells over time via transmission electron microscope. Immunohistochemistry and western blot assay revealed that valproate upregulated the expression of the endoplasmic reticulum stress marker glucose-regulated protein 78 and downregulated the expression of transcription factor C/EBP homologous protein, phosphorylated eukaryotic translation initiation factor 2α, and caspase-12 in the endoplasmic reticulum of retinal ganglion cells. These findings suggest that valproate reduces apoptosis of retinal ganglion cells in the rat after optic nerve-crush injury by attenuating phosphorylated eukaryotic translation initiation factor 2α-C/EBP homologous protein signaling and caspase-12 activation during endoplasmic reticulum stress. These findings represent a newly discovered mechanism that regulates how valproate protects neurons.

Diabetes mellitus is an established risk factor for periodontal disease that can aggravate the severity of periodontal inflammation and accelerate periodontal destruction. The chronic high glucose condition is a hallmark of diabetes-related pathogenesis, and has been demonstrated to impair the osteogenic differentiation of periodontal ligament stem cells (PDLSCs), leading to delayed recovery of periodontal defects in diabetic patients. Reactive oxygen species (ROS) are small molecules that can influence cell fate determination and the direction of cell differentiation. Although excessive accumulation of ROS has been found to be associated with high glucose-induced cell damage, the underlying mechanisms remain unclear. Nicotinamide adenine dinucleotide phosphate (NADPH) is an important electron donor and functions as a critical ROS scavenger in antioxidant systems. It has been identified as a key mediator of various biological processes, including energy metabolism and cell differentiation. However, whether NADPH is involved in the dysregulation of ROS and further compromise of PDLSC osteogenic differentiation under high glucose conditions is still not known. In the present study, we found that PDLSCs incubated under high glucose conditions showed impaired osteogenic differentiation, excessive ROS accumulation and increased NADPH production. Furthermore, after inhibiting the synthesis of NADPH, the osteogenic differentiation of PDLSCs was significantly enhanced, accompanied by reduced cellular ROS accumulation. Our findings demonstrated the crucial role of NADPH in regulating cellular osteogenic differentiation under high glucose conditions and suggested a new target for rescuing high glucose-induced cell dysfunction and promoting tissue regeneration in the future.

Abstract Periodontal ligament stem cells (PDLSCs) are a key cell type for restoring/regenerating lost/damaged periodontal tissues, including alveolar bone, periodontal ligament and root cementum, the latter of which is important for regaining tooth function. However, PDLSCs residing in an inflammatory environment generally exhibit compromised functions, as demonstrated by an impaired ability to differentiate into cementoblasts, which are responsible for regrowing the cementum. This study investigated the role of mitochondrial function and downstream long noncoding RNAs (lncRNAs) in regulating inflammation-induced changes in the cementogenesis of PDLSCs. We found that the inflammatory cytokine-induced impairment of the cementogenesis of PDLSCs was closely correlated with their mitochondrial function, and lncRNA microarray analysis and gain/loss-of-function studies identified GACAT2 as a regulator of the cellular events involved in inflammation-mediated mitochondrial function and cementogenesis. Subsequently, a comprehensive identification of RNA-binding proteins by mass spectrometry (ChIRP-MS) and parallel reaction monitoring (PRM) assays revealed that GACAT2 could directly bind to pyruvate kinase M1/2 (PKM1/2), a protein correlated with mitochondrial function. Further functional studies demonstrated that GACAT2 overexpression increased the cellular protein expression of PKM1/2, the PKM2 tetramer and phosphorylated PKM2, which led to enhanced pyruvate kinase (PK) activity and increased translocation of PKM2 into mitochondria. We then found that GACAT2 overexpression could reverse the damage to mitochondrial function and cementoblastic differentiation of PDLSCs induced by inflammation and that this effect could be abolished by PKM1/2 knockdown. Our data indicated that by binding to PKM1/2 proteins, the lncRNA GACAT2 plays a critical role in regulating mitochondrial function and cementogenesis in an inflammatory environment.

ObjectivesThe aim of this study is to assess the influence of cardiopulmonary coupling (CPC) based on RCMSE on the prediction of complications and death in patients with acute type A aortic dissection (ATAAD).BackgroundThe cardiopulmonary system may be nonlinearly regulated, and its coupling relationship with postoperative risk stratification in ATAAD patients has not been studied.MethodsThis study was a single-center, prospective cohort study (ChiCTR1800018319). We enrolled 39 patients with ATAAD. The outcomes were in-hospital complications and all-cause readmission or death at 2 years.ResultsOf the 39 participants, 16 (41.0%) developed complications in the hospital, and 15 (38.5%) died or were readmitted to the hospital during the two-year follow-up. When CPC-RCMSE was used to predict in-hospital complications in ATAAD patients, the AUC was 0.853 (p

Ras homolog (Rho)-associated kinases (ROCKs) belong to the serine-threonine kinase family, which plays a pivotal role in regulating the damage, survival, axon guidance, and regeneration of neurons. ROCKs are also involved in the biological effects of immune cells and glial cells, as well as the development of neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis. Previous studies by us and others confirmed that ROCKs inhibitors attenuated the symptoms and progression of experimental models of the abovementioned neurodegenerative diseases by inhibiting neuroinflammation, regulating immune imbalance, repairing the blood-brain barrier, and promoting nerve repair and myelin regeneration. Fasudil, the first ROCKs inhibitor to be used clinically, has a good therapeutic effect on neurodegenerative diseases. Fasudil increases the activity of neural stem cells and mesenchymal stem cells, thus optimizing cell therapy. This review will systematically describe, for the first time, the effects of abnormal activation of ROCKs on T cells, B cells, microglia, astrocytes, oligodendrocytes, and pericytes in neurodegenerative diseases of the central nervous system, summarize the therapeutic potential of fasudil in several experimental models of neurodegenerative diseases, and clarify the possible cellular and molecular mechanisms of ROCKs inhibition. This review also proposes that fasudil is a novel potential treatment, especially in combination with cell-based therapy. Findings from this review add support for further investigation of ROCKs and its inhibitor fasudil for the treatment of neurodegenerative diseases.

BackgroundThe adverse effects of smartphone addiction (SPA) and Internet gaming disorder (IGD) on adolescents’ mental health have been widely recognized. However, the influence of parenting styles on these high-risk Internet use behaviors of adolescents still remain elusive. Aiming to identify preventable patterns for adolescents with SPA or IGD, this study compared the mental health status between adolescents with SPA and IGD and used path analysis to confirm actual effects of parenting styles on SPA and IGD.MethodsParticipants were enrolled at a junior high school in Hunan Province and a senior high school in Shanxi Province, China [n = 3,049, female (male): 50.5% (49.5%), mean age = 15.68 ± 1.54]. All participants reported their socio-demographic characteristics and undertook standardized assessments of SPA, IGD, parenting styles, depression, anxiety, insomnia, self-control, and support utilization.ResultsHigh levels of parental care and low levels of parental overprotection benefited adolescents’ mental health with SPA and IGD. However, despite having a more positive parenting style, adolescents with only SPA showed more severe mental health problems than adolescents with only IGD. Furthermore, the results showed that the parenting style of encouraging autonomy might be a protective factor against IGD, but it might reinforce SPA indirectly by reducing abilities of support utilization and self-control in whole sample.ConclusionCompared to IGD, SPA which included different kinds of Internet addiction behaviors, was more hazardous for adolescents’ mental health. The divergent effects of an autonomy-encouraging parenting style on SPA and IGD may reflect the different impacts of self-control in different types of Internet addiction.

Duplex stainless steel (DSS) has been widely used in some harsh environments, such as flue gas shedding and seawater desalination, because of its high strength and corrosion resistance. These excellent properties rely on a high alloy content (Cr, Mo, N, etc.) and perfect dual-phase equilibrium. The dual-phase equilibrium mainly includes dual-phase proportion balance, properties balance, and absence of clear secondary phase in the solid solution structure. As one of the main developmental directions of DSS, hyper-duplex stainless steel (HDSS) has attracted much attention in recent years. In this paper, the effects of solution treatment on precipitates, microstructure, and properties of S32707 HDSS were studied by Thermo-Calc thermodynamic calculation, OM and FE-SEM observation, mechanical properties, and corrosion property tests. The results showed that σ phase and non-equilibrium nitrides were the main precipitates of solution-treated HDSS. When the solution temperature was lower than 1050 ℃, the σ phase precipitated preferentially along the dual-phase boundaries, which significantly reduced the impact toughness of HDSS. When the solution temperature was higher than 1100 ℃, non-equilibrium nitrides precipitated in ferrite grains, and the number of non-equilibrium nitrides increased with an increase in solution temperature. The reason for the non-equilibrium nitride precipitation was that the nitrogen content in the ferrite increased with an increase in temperature. This led to the supersaturation of nitrogen in the ferrite grains during the rapid cooling process. Under such conditions, the finely dispersed non-equilibrium nitrides precipitated in the ferrite grains. With increasing solution temperature, the content of the ferrite increased, the content of austenite decreased, the strength increased, and the impact toughness decreased. The optimal solution temperature of HDSS was 1080‒1120 ℃. Under this condition, the ratio of duplex was close to 1∶1, and the S32707 hyper duplex stainless steel presented excellent comprehensive mechanical properties and intergranular corrosion resistance.

Abstract Lung adenocarcinoma is heterogeneous and hierarchically organized, with a subpopulation of stem-like cells (CSCs) that reside at the apex of the hierarchy, in which exosomes act as important mediators by transporting specific molecules among different cell populations. Although there have been numerous studies on tumor exosomes, the constituents and functional properties of CSC-derived exosomes are still poorly characterized. Here we present a detail transcriptome and proteome atlas of the exosomes released by human lung adenocarcinoma stem-like cells (LSLCs). The transcriptome analysis indicates the specific patterns of exosomal constituents, including the fragmentation of transcripts and the low-level presence of circular RNAs, and identifies multiple exosomal-enriched mRNAs and lncRNAs. Integrative analysis of transcriptome and proteome data reveals the diverse functions of exosomal-enriched RNAs and proteins, many of which are associated with tumorigenesis. Importantly, several LSLC markers we identified are highly expressed in LSLC-derived exosomes and associate with poor survival, which may serve as promising liquid biopsy biomarkers for lung adenocarcinoma diagnosis. Our study provides a resource for the future elucidation of the functions of tumor-derived exosomes and their regulatory mechanisms in mediating lung cancer development.

Abstract. Background:. Fetal weight is an important parameter to ensure maternal and child safety. The purpose of this study was to use three-dimensional (3D) limb volume ultrasound combined with fetal abdominal circumference (AC) measurement to establish a model to predict fetal weight and evaluate its efficiency. Methods:. A total of 211 participants with single pregnancy (28–42 weeks) were selected between September 2017 and December 2018 in the Beijing Obstetrics and Gynecology Hospital of Capital Medical University. The upper arm (AVol)/thigh volume (TVol) of fetuses was measured by the 3D limb volume technique. Fetal AC was measured by two-dimensional ultrasound. Nine cases were excluded due to incomplete information or the interval between examination and delivery >7 days. The enrolled 202 participants were divided into a model group (134 cases, 70%) and a verification group (68 cases, 30%) by mechanical sampling method. The linear relationship between limb volume and fetal weight was evaluated using Pearson Chi-squared test. The prediction model formula was established by multivariate regression with data from the model group. Accuracy of the model formula was evaluated with verification group data and compared with traditional formulas (Hadlock, Lee2009, and INTERGROWTH-21st) by paired t-test and residual analysis. Receiver operating characteristic curves were generated to predict macrosomia. Results:. AC, AVol, and TVol were linearly related to fetal weight. Pearson correlation coefficient was 0.866, 0.862, and 0.910, respectively. The prediction model based on AVol/TVol and AC was established as follows: Y = −481.965 + 12.194TVol + 15.358AVol + 67.998AC, R2adj = 0.868. The scatter plot showed that when birth weight fluctuated by 5% (i.e., 95% to 105%), the difference between the predicted fetal weight by the model and the actual weight was small. A paired t-test showed that there was no significant difference between the predicted fetal weight and the actual birth weight (t = −1.015, P = 0.314). Moreover, the residual analysis showed that the model formula's prediction efficiency was better than the traditional formulas with a mean residual of 35,360.170. The combined model of AVol/TVol and AC was superior to the Lee2009 and INTERGROWTH-21st formulas in the diagnosis of macrosomia. Its predictive sensitivity and specificity were 87.5% and 91.7%, respectively. Conclusion:. Fetal weight prediction model established by semi-automatic 3D limb volume combined with AC is of high accuracy, sensitivity, and specificity. The prediction model formula shows higher predictive efficiency, especially for the diagnosis of macrosomia. Trial Registration:. ClinicalTrials.gov, NCT03002246; https://clinicaltrials.gov/ct2/show/NCT03002246?recrs=e&cond=fetal&draw=8&rank=67.

Astrocytes play multifaceted and vital roles in maintaining neurophysiological function of the central nervous system by regulating homeostasis, increasing synaptic plasticity, and sustaining neuroprotective effects. Astrocytes become activated as a result of inflammatory responses during the progression of pathological changes associated with neurodegenerative disorders. Reactive astrocytes (neurotoxic A1 and neuroprotective A2) are triggered during disease progression and pathogenesis due to neuroinflammation and ischemia. However, only a limited body of literature describes morphological and functional changes of astrocytes during the progression of neurodegenerative diseases. The present review investigated the detrimental and beneficial roles of astrocytes in neurodegenerative diseases reported in recent studies, as these cells have promising therapeutic potential and offer new approaches for treatment of neurodegenerative diseases.

AIM: To analyze the problems faced by teachers and undergraduates online teaching. METHODS:A self-designed questionnaire survey and result of examination comparison were used. The contents of the questionnaire include the time used before and after class, the confusion faced by online teaching and the self-evaluation of teaching effect. 63 students and all teachers were participants in the questionnaire survey. The survey is from May 2020 to June 2020.RESULTS: The average time spent by students before class of online teaching had no difference with that of offline teaching, while the average time spent by teachers for online teaching before class was significantly longer than that for offline teaching. 63% of the undergraduates considered that online teaching takes much more time to review after class. 95% of the students admitted that online teaching was easier to lose concentration because of lack of interaction with teachers, and 73% of teachers though that for online teaching they had less passionate compared to off line teaching. Regarding to the questionnaire survey, 73% of the instructors expected that the effect of online teaching would be worse than that of offline teaching. Surprisingly, 95% of the students thought that there had no significant difference in knowledge mastering between online and offline teaching after reviewing of courseware. For the future teaching model, 91% of the teachers and 79% of the students preferred the combination of watching pre-recorded video and live broadcasting. CONCLUSION: The lack of interaction is the primary issue of online teaching. Online teaching can achieve the same effect as offline teaching,whereas it needs more post-class time for students. The combination of watching pre-recorded video and live-broadcasting is the online teaching mode recommended by teachers and students.

Recent studies have shown that Nogo-A and the Nogo-A receptor affect β-amyloid metabolism and the downstream Rho GTP enzyme signaling pathway, which may affect the levels of β-amyloid and tau. Nogo-A may play a key role in the pathogenesis of Alzheimer's disease. However, the underlying molecular mechanisms of Fasudil treatment in Alzheimer's disease are not yet clear. Our results have found that Fasudil treatment for two months substantially ameliorated behavioral deficits, diminished β-amyloid plaque and tau protein pathology, and alleviated neuronal apoptosis in APP/PS1 transgenic mice. More importantly, two well-established markers for synaptic function, growth-associated protein 43 and synaptophysin, were upregulated after Fasudil treatment. Finally, the levels of Nogo-A, Nogo-A receptor complex NgR/p75NTR/LINGO-1 and the downstream Rho/Rho kinase signaling pathway were significantly reduced. These findings suggest that Fasudil exerts its neuroprotective function in Alzheimer's disease by inhibiting the Nogo-A/NgR1/RhoA signaling pathway.

Abstract. The homeostasis of the gut-brain axis has been shown to exert several effects on physiological and psychological health. The gut hormones released by enteroendocrine cells scattered throughout the gastrointestinal tract are important signaling molecules within the gut-brain axis. The interaction between gut microbiota and gut hormones has been greatly appreciated in gut-brain cross-talk. The microbiota plays an essential role in modulating many gut-brain axis-related diseases, ranging from gastrointestinal disorders to psychiatric diseases. Similarly, gut hormones also play pleiotropic and important roles in maintaining health, and are key signals involved in gut-brain axis. More importantly, gut microbiota can affect the release and functions of gut hormones. This review highlights the role of gut microbiota in the gut-brain axis and focuses on how microbiota-related gut hormones modulate various physiological functions. Future studies could target the microbiota-hormones-gut brain axis to develop novel therapeutics for different psychiatric and gastrointestinal disorders, such as obesity, anxiety, and depression.

Tetracyclines are one class of widely used antibiotics. Meanwhile, due to abuse and improper disposal, they are often detected in wastewater, which causes a series of environmental problems and poses a threat to human health and safety. As an efficient and environmentally friendly method, enzymatic catalysis has attracted much attention. In previous studies, we have designed an efficient peroxidase (F43Y/P88W/F138W Mb, termed YWW Mb) based on the protein scaffold of myoglobin (Mb), an O2 carrier, by modifying the heme active center and introducing two Trp residues. In this study, we further applied it to degrade the tetracycline antibiotics. Both UV-Vis and HPLC studies showed that the triple mutant YWW Mb was able to catalyze the degradation of tetracycline, oxytetracycline, doxycycline, and chlortetracycline effectively, with a degradation rate of ~100%, ~98%, ~94%, and ~90%, respectively, within 5 min by using H2O2 as an oxidant. These activities are much higher than those of wild-type Mb and other heme enzymes such as manganese peroxidase. As further analyzed by UPLC-ESI-MS, we identified multiple degradation products and thus proposed possible degradation mechanisms. In addition, the toxicity of the products was analyzed by using in vitro antibacterial experiments of E. coli. Therefore, this study indicates that the engineered heme enzyme has potential applications for environmental remediation by degradation of tetracycline antibiotics.

Alpine musk deer, Moschus chrysogaster, a solitary, primitive ungulate inhabiting high elevation areas (3000–4500 m) is an endangered species facing threat of extinction globally due to excessive hunting for its musk. In this study, we determined the complete mitochondrial genome of M. chrysogaster, which was 16,354 bp in length, and revealed the same gene order and genomic organization as typical Moschidae mitochondrial DNA. Start codons in 13 protein-coding genes (PCGs) were all typical ATGs except ATA for ND2 and ND3 and ATT for ND5. Stop codons were all typical types except an incomplete stop codon T for COX3, ND2, ND3, and ND4. Secondary structures in 22 transfer RNA genes all showed typical cloverleaf except tRNA-Ser (AGY), in which the dihydrouridine arm formed a simple loop. No repeat units were found in the control region. The topology structure indicated that M. cupreus was primitive and located at the root of the Moschidae clade. Phylogenetic reconstruction placed M. chrysogaster as a distinct lineage, closely related to the branch of M. leucogaster, M. berezovskii (wild) and predicted a sister relationship with M. moschiferus, M. anhuiensis, and M. berezovskii (captive). However, we suggested that the genetic resources of M. chrysogaster_JQ608470 should be further investigated.

Abstract Background To analyze the collaboration and reporting quality of the systematic reviews of social welfare in the Campbell collaboration online library. Methods The Campbell collaboration online library was searched for systematic reviews of social welfare and the basic information extracted in order to assess the reporting quality of systematic reviews using a MOOSE checklist. BICOMS-2 and UCINET software were used to produce the social network, and Comprehensive Meta Analysis (Version 2) and STATA 13.0 were used to analyze the related data. Results Fifty-seven systematic reviews of social welfare were included. Twenty-eight items of the included social welfare systematic reviews were rated as complete (≥70%). There were significant differences between ≤2013 and ≥ 2014 in five items. These differences were as follows: research published by one organization or more than one organization in one item, more than three authors or less than four authors in two items, and one country or more than one country in six items. It’s completed about researches with more than one organization, three authors or more than one country. Some items were found to have a low reporting rate of studies published before 2014, by one organization, with less than four authors or one country, respectively. The social network of authors and organizations showed good collaboration. Conclusions Some items could be further improved with regard to the rate of reporting systematic reviews of social welfare in the Campbell collaboration online library. This could improve the overall quality of social welfare systematic reviews.

Abstract This study aimed to investigate the relationship between inflammation‐related T‐helper cell polarization and the receptor activator for nuclear factor‐κB ligand (RANKL)/osteoprotegerin (OPG) ratio, which is associated with bone resorption or remodeling of chronic periodontitis patients. Gingival crevicular fluid (GCF) and gingival tissues were obtained from periodontally healthy individuals (PH group) and chronic periodontitis patients (CP group). The GCF levels of IFN‐γ, IL‐4, IL‐17, and IL‐10 linked to T‐helper cell polarization toward the Th1, Th2, Th17, and Treg phenotypes, respectively, were determined by ELISA. The expression levels of these cytokines and the polarized T‐helper cells in gingival tissues were assessed through immunohistochemical and immunofluorescence assays. In addition, the RANKL and OPG expression levels in gingival tissues were detected by immunohistochemical assays, and linear regression analysis was used to identify the potential relationship between T‐helper cell polarization and the RANKL/OPG ratio. In total, 22 individuals and 35 patients were enrolled in the present study. In both GCF and gingival tissues, increased levels of IL‐17 and the decreased levels of IL‐4 and IL‐10 were observed in the CP group. When polarized T‐helper cells were identified in gingival tissues, more Th1 and Th17 cells were found in the CP group, whereas more Th2 and Treg cells were found in the PH group. Although there was no significant difference in OPG expression between the two groups, the RANKL/OPG ratio in the CP group was higher than that in the PH group. The linear regression analysis showed that the presence of more Th1 and Th17 cells correlated with a higher RANKL/OPG ratio, whereas the presence of more Th2 cells correlated with a lower RANKL/OPG ratio. Th1 and Th17 cells are positively correlated and Th2 cells are negatively correlated with the RANKL/OPG ratio. Our data suggest that T‐helper cell polarization is closely linked to the RANKL/OPG ratio in gingival tissues from chronic periodontitis patients.

Background/purpose: Stimuli from the oral cavity may penetrate through exposed dentinal tubules and evoke inflammatory pulp response. Anti-bacterial and anti-inflammatory drugs applied to exposed dentin may infiltrate through the dentinal tubules and cause pulp recovery. This study investigated the dentin permeability of anti-bacterial and anti-inflammation drugs via an in-vitro transwell dentin disc tube model. Methods: Twenty-seven dentin discs prepared from extracted human molars were collected. Nine kinds of drugs were investigated with three dentin discs in each group. These nine drugs included two anti-bacterial drugs (ampicillin sodium and clindamycin phosphate), two corticosteroids (betamethasone sodium phosphate and hydrocortisone sodium succinate), three non-steroidal anti-inflammatory drugs (NSAIDs, piroxicam, lysine acetylsalicylate, and diclofenac sodium), and two natural extracts with anti-inflammatory effect (Ginsenoside Rg1 and Hinokitol). The drugs were introduced to the transwell dentin disc tube model and the 4-hour cumulative release of the drug was detected and recorded by UV-visible spectroscopy. Results: We found that ampicilin sodium had better dentin permeability than clindamycin phosphate. Betamethasone sodium phosphate revealed better dentin permeability than hydrocortisone sodium succinate. Lysine acetylsalicylate showed the best dentin permeability among the three NSAIDs. Ginsenoside Rg1 had the best dentin permeability among the nine drugs tested. However, Hinokitiol could not penetrate the dentin disc after 4 h. Conclusion: Regarding the dentin permeability, Ginsenoside Rg1 is the best among the seven anti-inflammatory drugs tested and ampicilin sodium is the better one between the two anti-bacterial drugs tested. Therefore, these two drugs may have high potential for treating exposed dentinal tubule diseases. Keywords: Anti-bacterial agents, Anti-inflammatory agents, Dentin permeability, Exposed dentinal tubules

Objective This study aimed to investigate the protective effects of naringin on myocardial deformation and oxidative responses in rats with sepsis-induced myocardial dysfunction (SIMD). Methods Global and segmental layer-specific longitudinal strain (LS) was assessed by speckle tracking echocardiography. Serum levels of creatine kinase, lactate dehydrogenase, superoxide dismutase, and malondialdehyde were measured. The activity of cleaved caspase-3 was determined by immunohistochemistry. Protein expression levels of Kelch-like ECH-related protein 1 (Keap1), nuclear erythroid factor 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) were measured by western blotting. Results Naringin inhibited the lipopolysaccharide-induced decrease in global and layer-specific LS of the left ventricle. Naringin also increased superoxide dismutase expression and decreased malondialdehyde, creatine kinase, lactate dehydrogenase, and cleaved caspase-3 expression in rats with SIMD. Furthermore, naringin increased Nrf2 and HO-1 protein expression levels, and decreased Keap1 protein expression levels in rats with SIMD. Conclusion Layer-specific LS analysis of myocardial function by speckle tracking echocardiography can reflect early changes in myocardial systolic function. Naringin may possess a protective effect through moderating lipopolysaccharide-induced myocardial oxidative stress via the Keap1/Nrf2/HO-1 pathway in rats with SIMD.

Mild traumatic brain injury (mTBI), or concussion, is reported to interfere with cerebral blood flow and microcirculation in patients, but our current understanding is quite limited and the results are often controversial. Here we used longitudinal in vivo two-photon imaging to investigate dynamic changes in cerebral vessels and velocities of red blood cells (RBC) following mTBI. Closed-head mTBI induced using a controlled cortical impact device resulted in a significant reduction of dwell time in a Rotarod test but no significant change in water maze test. Cerebral blood vessels were repeatedly imaged through a thinned skull window at baseline, 0.5, 1, 6 h, and 1 day following mTBI. In both arterioles and capillaries, their diameters and RBC velocities were significantly decreased at 0.5, 1, and 6 h after injury, and recovered in 1 day post-mTBI. In contrast, decreases in the diameter and RBC velocity of venules occurred only in 0.5–1 h after mTBI. We also observed formation and clearance of transient microthrombi in capillaries within 1 h post-mTBI. We concluded that in vivo two-photon imaging is useful for studying earlier alteration of vascular dynamics after mTBI and that mTBI induced reduction of cerebral blood flow, vasospasm, and formation of microthrombi in the acute stage following injury. These changes may contribute to early brain functional deficits of mTBI.

Chromatin dynamics regulated by epigenetic modification is crucial in genome stability and gene expression. Various epigenetic mechanisms have been identified in the pathogenesis of human diseases. Here, we examined the effects of ten epigenetic agents on pseudorabies virus (PRV) infection by using GFP-reporter assays. Inhibitors of bromodomain protein 4 (BRD4), which receives much more attention in cancer than viral infection, was found to exhibit substantial anti-viral activity against PRV as well as a range of DNA and RNA viruses. We further demonstrated that BRD4 inhibition boosted a robust innate immune response. BRD4 inhibition also de-compacted chromatin structure and induced the DNA damage response, thereby triggering the activation of cGAS-mediated innate immunity and increasing host resistance to viral infection both in vitro and in vivo. Mechanistically, the inhibitory effect of BRD4 inhibition on viral infection was mainly attributed to the attenuation of viral attachment. Our findings reveal a unique mechanism through which BRD4 inhibition restrains viral infection and points to its potent therapeutic value for viral infectious diseases.

AIM: To investigate the roles of integrins in choroidal neovascularization (CNV) and their associations with the stromal cell-derived factor-1 (SDF-1)/CXCR4 axis. METHODS: CNV lesions were induced in mice using laser photocoagulation. After CNV induction, all animals were randomly assigned to: control, SDF-1, SDF-1+age-related macular degeneration (AMD) 3100 (CXCR4 inhibitor), and SDF-1+ATN161 (integrin α5β1 inhibitor) groups; their effects on CNV progression were observed using hematoxylin eosin (HE) staining, fundus fluorescein angiography (FFA) grading and optical coherence tomography (OCT), and their effects on CXCR4/integrin α5 expression were evaluated using Western blot and double immunofluorescence staining. Hypoxia-exposed endothelial cells (ECs) were used to simulate CNV in vitro, they were treated with SDF-1, combined with CXCR4 siRNA/AMD3100 or ATN161, and expression of integrin α5, cell migration and tube formation were analyzed. RESULTS: Integrin subunit α5 increased at 3rd and 7th day and decreased at 14th day in CNV mice, with no significant change of β1-integrin. CXCR4 expression in CNV mice had persistent increase within 14d after induction. SDF-1 treatment significantly promoted the CNV progression during 3-14d. The mean CNV length in AMD3100 and ATN161 group at day 7 was 270.13 and 264.23 μm in HE images, significantly lower than the mean length in SDF-1 (345.70 μm) group. AMD3100 and ATN161 also significantly reduced thickness and leakage of CNV induced by SDF-1. Mean integrin α5 positive area in SDF-1 group reached 2.31×104 μm2, significantly higher than control (1.25×104 μm2), which decreased to 1.78×104 μm2 after AMD3100 treatment. About 61.36% of ECs in CNV lesions expressed α5 in SDF-1 group, which significantly decreased to 43.12% after AMD3100 treatment. In vitro, integrin α5 peaked by 6 folds after 6h of hypoxia exposure and CXCR4 gradually increased by up to 2.3 folds after 24h of hypoxia. Approximately 25.12% of ECs expressed integrin α5 after SDF-1 stimulation, which decreased to 7.2%-9.5% after si-CXCR4 or AMD3100 treatment. ATN161 exerted an inhibitory effect comparable to that of si-CXCR4 on EC migration and tube formation in the presence of SDF-1. CONCLUSION: SDF-1/CXCR4 signaling induces integrin α5β1 expression in ECs to promote CNV.

Abstract Poly-methyl methacrylate (PMMA)-based dental resins with strong and long-lasting antifungal properties are critical for the prevention of denture stomatitis. This study evaluated the antifungal effects on Candida albicans ATCC90028, the cytotoxicity toward human dental pulp cells (HDPCs), and the mechanical properties of a silver bromide/cationic polymer nano-composite (AgBr/NPVP)-modified PMMA-based dental resin. AgBr/NPVP was added to the PMMA resin at 0.1, 0.2, and 0.3 wt%, and PMMA resin without AgBr/NPVP served as the control. Fungal growth was inhibited on the AgBr/NPVP-modified PMMA resin compared to the control (P 0.05) between the experimental and control groups. These data indicate that the incorporation of AgBr/NPVP conferred strong and long-lasting antifungal effects against Candida albicans to the PMMA resin, and it has low toxicity toward HDPCs, and its mechanical properties were not significantly affected.

Objective We investigated the risk of acute and late toxicities of concurrent chemoradiotherapy (CCRT) and radiotherapy alone in patients with nasopharynx carcinoma (NPC). Methods In this meta-analysis, we searched the PubMed, Embase, Cochrane Library, and Web of Science databases for eligible randomized clinical trials (RCTs). In addition to the incidence of specific toxicities, risk ratios (RRs) or odd ratios (ORs) and 95% confidence intervals (CIs) were obtained using fixed-effect or random-effects models. Results In total, 11 RCTs involving 2801 patients with NPC were included in this analysis. For grade ≥3 adverse events, patients who received CCRT treatment had a higher proportion of acute mucositis (39.9% vs. 30.5%, RR=1.30, 95%CI, 1.16–1.46) acute nausea and vomiting (RR=6.26, 95% CI: 2.01–19.45), and neutropenia (RR=30.86, 95% CI: 7.36 to 129.35). For late severe toxicities, CCRT treatment was significantly associated with higher incidence of hearing loss (116.56% vs. 411.43%, RR=1.461, 95%CI, 1.043–21.095). The incidence of acute nausea and vomiting was more frequent in patients receiving CCRT. Conclusion Compared with radiotherapy alone, CCRT increases the risk of severe acute toxicities (mucositis, nausea/vomiting, and neutropenia) and severe late toxicity (hearing loss) in patients with NPC. However, larger studies are needed to confirm this finding.

Currently, insecticides are considered as the primary approach for controlling western flower thrips, Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae). However, the heavy use of insecticides resulted in high insect resistance and serious environmental pollution. Given its characteristics of ease of operation and environmental friendliness, insect control using high temperature is receiving considerable renewed research interest. However, although the combination of insecticides and high temperature to control F. occidentalis has been studied before, few studies have focused on the short-term effect of such treatment. In a laboratory study, F. occidentalis adults and second-instar nymphs were exposed to 45°C for 2 h. Then, their susceptibility to acetamiprid, spinosad, methomyl, and beta-cypermethrin was tested after different periods of recovery time (2–36 h). Additionally, the specific activity of three detoxification enzymes (esterase, glutathione S-transferase, and cytochrome p450 (CYP) monooxygenase) of the treated insects was determined. The results indicated that the fluctuation of susceptibility to insecticides and detoxification enzyme activity during F. occidentalis recovery from heat shock are related. Furthermore, several recovery time points (2, 30, and 36 h) of significant susceptibility to four tested insecticides compared with the control were found during the treatment of adults that were heat-shocked. Recovery time points of higher susceptibility compared with the control depended on different insecticides during the second-instar nymph recovery from heat shock. Interestingly, the fluctuation of CYP monooxygenase activity exhibited a trend that was similar to the fluctuation of susceptibility to insecticides (especially spinosad) during the recovery from heat shock of adults. In addition, the glutathione S-transferase and CYP monooxygenase activity trend was similar to the trend of susceptibility to spinosad during the recovery from heat shock of second-instar nymphs. Our results provide a new approach for controlling F. occidentalis using the combined heat shock and insecticide. This effectively enhances the control efficiency of heat shock and significantly reduces the application of insecticides.

For the inevitable uncertainty and random uncertainty in the process of measuring water quality data with the sensor network,a multi-sensor data fusion method for water quality evaluation based on interval evidence theory was proposed.Considering the precision error of sensor and the abnormalities of measured data,every water quality data measured by sensor was represented by interval number.By calculating the distance between the water quality data and the features of each water quality class,the interval evidence of water quality class was acquired.According to the interval evidence combining rule,a comprehensive interval evidence was obtained by combining the interval evidence of each sensor.Finally,the water quality class was determined based on the comprehensive interval evidence by the decision rule.Experiments show that the proposed method can evaluate water quality class more accurately from the uncertain water quality data.

Objective This study aimed to examine the relationship between serum iron levels and in-hospital mortality in critically ill patients. Methods We retrospectively studied 250 critically ill patients who received treatment at the intensive care unit between June 2015 and May 2017. Blood chemistry and hepatic and renal function were measured. Kaplan–Meier survival curves were plotted according to serum iron levels. Correlations between serum iron levels and other variables were analyzed. Results A total of 165 (66.0%) patients had abnormally low serum iron levels (

A novel technique is proposed in this paper for shared aperture multibeam forming in a complex time-modulated linear array. First, a uniform line array is interleaved randomly to form two sparse array subarrays. Subsequently, the theory of time modulation for linear arrays is applied in the constructed subarrays. In the meantime, the switch-on time sequences for each element of the two subarrays are optimized by an optimized differential evolution (DE) algorithm, i.e., the scaling factor of the sinusoidal iterative chaotic system and the adaptive crossover probability factor are used to enhance the diversity of the population. Lastly, the feasibility of the new technique is verified by the comparison between this technique and the basic multibeam algorithm in a shared aperture and the algorithm of iterative FFT. The results of simulations confirm that the proposed algorithm can form more desired beams, and it is superior to other similar approaches.

Moschus berezovskii is an endangered species, but its captive populations are valuable on musk secretions in traditional Chinese medicine and perfume manufacture. The mitogenome of M. berezovskii was 16,353 bp in size. Stop codons in 13 PCGs were all typical types except incomplete stop codon T for COX3, ND2 and ND4, and TA for ND3. No tandem repeat was found in control region. Phylogenetic analysis indicated that Moschidae has the closest relationship with Bovidae. We supported that M. berezovskii should be categorized into two subspecies, and suggested that the status of M. chrysogaster JQ608470 should be further investigated.

Intranasal vaccination is more potent than parenteral injection for the prevention of influenza. However, because the poor efficiency of antigen uptake across the nasal mucosa is a key issue, immunostimulatory adjuvants are essential for intranasal vaccines. The immunomodulator mannatide or polyactin (PA) has been used for the clinical treatment of impaired immunity in China, but its adjuvant effect on an inactivated trivalent influenza vaccine (ITIV) via intranasal vaccination is unclear. To explore the adjuvant effect of PA, an inactivated trivalent influenza virus with or without PA or MF59 was instilled intranasally once a week in BALB/c mice. Humoral immunity was assessed by both the ELISA and hemagglutination inhibition (HI) methods using antigen-specific antibodies. Splenic lymphocyte proliferation and the IFN-γ level were measured to evaluate cell-mediated immunity. The post-vaccination serum HI antibody geometric mean titers (GMTs) for the H1N1 and H3N2 strains, antigen-specific serum IgG and IgA GMTs, mucosal SIgA GMT, splenic lymphocyte proliferation, and IFN-γ were significantly increased in the high-dose PA-adjuvanted vaccine group. The seroconversion rate and the mucosal response for the H3N2 strain were significantly elevated after high-dose PA administration. These adjuvant effects of high-dose PA for the influenza vaccine were comparable with those of the MF59 adjuvant, and abnormal signs or pathological changes were not found in the evaluated organs. In conclusion, PA is a novel mucosal adjuvant for intranasal vaccination with the ITIV that has safe and effective mucosal adjuvanticity in mice and successfully induces both serum and mucosal antibody responses and a cell-mediated response.

The issue of data collection in wireless sensor networks was studied.A mobile sink-based data collection scheme called DCSR was proposed.DCSR consisted of two phases.Firstly,a number of collection sites were selected according to the sensor distribution.And then a quantum genetic algorithm was performed to calculate the shortest loop across the sites.The sink node would travel along this loop periodically and collect data at each site.Theoretical analysis and simulation results show that DCSR has better performance and collects more data.

With the expansion of Intelligent Transport Systems (ITS) in smart cities, the shared bicycle has developed quickly as a new green public transportation mode, and is changing the travel habits of citizens heavily across the world, especially in China. The purpose of the current paper is to provide an inclusive review and survey on shared bicycle besides its benefits, history, brands and comparisons. In addition, it proposes the concept of the Internet of Shared Bicycle (IoSB) for the first time, as far as we know, to find a feasible solution for those technical problems of the shared bicycle. The possible architecture of IoSB in our opinion is presented, as well as most of key IoT technologies, and their capabilities to merge into and apply to the different parts of IoSB are introduced. Meanwhile, some challenges and barriers to IoSB’s implementation are expressed thoroughly too. As far as the advice for overcoming those barriers be concerned, the IoSB’s potential aspects and applications in smart city with respect to technology development in the future provide another valuable further discussion in this paper.

OBJECTIVES: To investigate the effect of air-drying pressure during ceramic primer coating on zirconia/resin bonding and the surface characteristics of the primed zirconia. METHODS: Two ceramic primers (Clearfil Ceramic Primer, CCP, Kuraray Medical Inc. and Z-Prime Plus, ZPP, Bisco Inc.) were applied on the surface of air-abraded zirconia (Katana zirconia, Noritake) and dried at 4 different air pressures (0.1-0.4 MPa). The primed zirconia ceramic specimens were bonded with a resin-based luting agent (SA Luting Cement, Kuraray). Micro-shear bond strengths of the bonded specimens were tested after 3 days of water storage or 5,000× thermocycling (n = 12). Failure modes of the fractured specimens were examined with scanning electron miscopy. The effects of air pressure on the thickness of the primer layers and the surface roughness (Sa) of primed zirconia were evaluated using spectroscopic ellipsometry (n = 6), optical profilometry and environmental scanning electron microscopy (ESEM) (n = 6), respectively. RESULTS: Clearfil Ceramic Primer air-dried at 0.3 and 0.4 MPa, yielding significantly higher µSBS than gentle air-drying subgroups (p < 0.05). Compared to vigorous drying conditions, Z-Prime Plus air-dried at 0.2 MPa exhibited significantly higher µSBS (p < 0.05). Increasing air-drying pressure reduced the film thickness for both primers. Profilometry measurements and ESEM showed rougher surfaces in the high pressure subgroups of CCP and intermediate pressure subgroup of ZPP. CONCLUSION: Air-drying pressure influences resin/zirconia bond strength and durability significantly. Higher air-drying pressure (0.3-0.4 MPa) for CCP and intermediate pressure (0.2 MPa) for ZPP are recommended to produce strong, durable bonds between resin cement and zirconia ceramics.

Objective: To investigate the dynamic expression of transforming growth factor-β1 (TGF-β1) and heat shock protein 47 (HSP47) and explore their roles in the progression of hepatic fibrosis induced by Schistosoma japonicum infection., Methods: Fifty female mice of the ICR strain were randomly divided into the infection group and the normal control group, of 25 mice in each group. Each mouse in the infection group was infected with 20 ± 1 cercariae of S. japonicum via the abdominal skin, while uninfected animals served as normal control. Five mice were sacrificed 4, 6, 8, 10 and 12 weeks post-infection and liver tissues were sampled. Serum HSP47 and TGF-β1 was determined using enzyme-linked immunosorbent assay (ELISA), and the pathological changes of liver specimens were observed with hematoxylin & eosin (HE) staining. In addition, the synthesis of alpha 1 chain of type I collagen (COL1A1) was measured using Masson staining, and the mRNA expression of TGF-β1 , HSP47 and COL1A1 was determined using real-time fluorescent quantitative PCR (qPCR) assay., Results: During the period of S. japonicum -induced hepatic fibrosis, the serum HSP47 and TGF-β1 levels and the mRNA expression of TGF - β 1 , HSP47 and COL1A1 gradually increased with the progression of hepatic fibrosis. The serum levels of HSP47 and TGF-β1 were (179.26 ± 29.87) pg/mL and (22.37 ± 5.21) ng/mL 6 weeks post-infection, respectively, which were significantly greater than those [(150.29 ± 34.91) pg/mL and (18.54 ± 7.78) ng/mL, respectively] in the normal control group (both P values < 0.05). In addition, the mRNA expression of HSP47 , COL1A1 and TGF- β 1 was (0.86 ± 0.04), (1.17 ± 0.06) and (0.64 ± 0.13) in mouse liver specimens, which was significantly higher than that (0.23 ± 0.03, 0.20 ± 0.02 and 0.38 ± 0.02) in the normal control group (all P values < 0.01)., Conclusions: The expression of TGF-β1 and HSP47 during the period of S. japonicum -induced hepatic fibrosis is consistent with the progression of the hepatic fibrosis, and exhibits the same tendency with type I collagen expression. HSP47 is a novel promising diagnosis marker and therapeutic target for S. japonicum -induced hepatic fibrosis.

Exosomes are a group of membraneous vesicles generated and released by multi-vesicular bodies or cell membranes in a variety of cell types. Acting as important messages between cells, they participate in almost every physiological and pathological process of living organisms. Exosomes contain specific proteins, mRNA, miRNAs, etc. and mediate intercellular communications, signal transductions and gene expressions effectively. Exosomes are involved in the formation of hepatic fibrosis, which is the typical liver pathological change in the progression of schistosomiasis and is caused by the liver repair and (or) regeneration involving inflammation stimulated by exosomes, activated hepatic stellate cells and other related pathways in reaction to the parasite infection. Exosomes could serve as new markers for schistosomiasis hepatic fibrosis diagnosis and potential targets for its treatment. This paper briefly reviews the latest development of studies on the regulatory roles of exosomes in schistosomiasis hepatic fibrosis, so as to provide ideas for searching new treatment targets of the disease.

Betel-quid use is associated with the risk of liver cirrhosis and hepatocellular carcinoma. The aim of the present work was to evaluate the impact of arecoline on human hepatic cytochrome P450 (CYP) enzymes in vitro and rat hepatic CYP enzymes, as well as the hepatic oxidative stress and liver injury of rats in vivo. The in vitro results indicated that arecoline hydrobromide (AH) has no significant effect on the activities of CYP2B, 2C9, 3A4, 1A2, 2E1 and 2D6 in human liver microsome (HLM). However, oral administration of AH at 4 and 20 mg/kg/d for seven consecutive days significantly increased the activities of rat hepatic CYP2B, 2E1, 2D, 3A, 2C and 1A2. In addition, AH at 100 mg/kg/d significantly increased the levels of ALT, AST and MDA, decreased the levels of SOD, CAT, GSH-Px and GSH, in rat liver. The in vivo induction of AH on rat hepatic CYP isoforms suggested that the high risk of metabolic interaction should be existed when the substrate drugs of the six kinds of CYP isoforms was administered in betel-quid use human. Furthermore, the in vivo results also suggested that AH-induced hepatoxicity should be associated with the induction of AH on rat hepatic CYP2E1 and 2B.