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Studies have shown that disulfiram (DSF) can combine with Cu

BackgroundThe effect of chronic psychological stress on hepatitis and liver fibrosis is concerned. However, its mechanism remains unclear. We investigated the effect and mechanism of chronic psychological stress in promoting liver injury and fibrosis through gut.MethodsSixty male SD rats were randomly assigned to 6 groups. Rat models of chronic psychological stress (4 weeks) and liver fibrosis (8 weeks) were established. The diversity of gut microbiota in intestinal feces, permeability of intestinal mucosa, pathologies of intestinal and liver tissues, collagen fibers, protein expressions of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear factor kappa β (NF-κβ), tumor necrosis factor α (TNF-α) and interleukin 1 (IL-1) in liver tissue, liver function and coagulation function in blood and lipopolysaccharide (LPS) in portal vein blood were detected and analyzed.ResultsThe diversities and abundances of gut microbiota were significant differences in rats among each group. The pathological lesions of intestinal and liver tissues, decreased expression of occludin protein in intestinal mucosa, deposition of collagen fibers and increased protein expression of TLR4, MyD88, NF-κβ, TNF-α and IL-1 in liver tissue, increased LPS level in portal vein blood, and abnormalities of liver function and coagulation function, were observed in rats exposed to chronic psychological stress or liver fibrosis. There were significant differences with normal rats. When the dual intervention factors of chronic psychological stress and liver fibrosis were superimposed, the above indicators were further aggravated.ConclusionChronic psychological stress promotes liver injury and fibrosis, depending on changes in the diversity of gut microbiota and increased intestinal permeability caused by psychological stress, LPS that enters liver and acts on TLR4, and active LPS-TLR4 pathway depend on MyD88. It demonstrates the possibility of existence of brain-gut-liver axis.

We aimed to elicit strong blinks among healthy video display terminal (VDT) users by periorbital transcutaneous electric nerve stimulation (TENS) and evaluate its impact on the tear fluid and visual task. Appropriate TENS conditions were evaluated to evoke strong blinks under minimum discomfort. Seventeen healthy VDT users with noninvasive Keratograph first breakup time (NIKf-BUT) 5-15 s and Ocular Surface Disease Index (OSDI) scores15 were recruited in this study. Before the trial, noninvasive Keratograph average breakup time (NIKa-BUT), tear meniscus height (TMH) and OSDI scores were evaluated. Before each TENS session, the volunteers played Tetris while the corresponding blink rate and Tetris scores were recorded. Then, the participants underwent 30 minutes of TENS, which evoked blinking of their right eye 20 times per minute. Tetris scores were evaluated again during TENS. The Tetris scores and corresponding blink rate were assessed after each TENS session while NIKa-BUT, TMH and OSDI scores were recorded after the third and sixth TENS sessions. We found that OSDI scores declined significantly after the sixth TENS (P = .003). The NIKa-BUT of the right eye was promoted after the sixth TENS (P = .02), and the TMH was higher after the third and sixth TENS in both eyes (P = .03, P = .03 for right eyes respectively, P = .01, P = .01 for left eyes respectively). There was no significant difference between the adjusted Tetris scores before and during TENS (P = .12). The blink rate before and after TENS were unaffected after 6 sessions (P = .61). The results indicated that periorbital TENS effectively ameliorated ocular irritation and improved tear secretion and tear film stability by eliciting strong blinks in healthy VDT users without disturbing the visual task.

Shared decision-making (SDM) is a scientific and reasonable decision-making model. However, whether physicians choose SDM is usually influenced by many factors. It is not clear whether the strained doctor–patient relationship will affect physicians' willingness to choose SDM. Through a survey by questionnaire, 304 physicians' evaluations of doctor–patient relationship (DPR) were quantified by the difficult DPR questionnaire-8. Their preferences for SDM and the reasons were also evaluated. The correlation between physicians' evaluations of DPR and their preferences for SDM were analyzed. 84.5% physicians perceived DPR as poor or strained, 53.3% physicians preferred SDM, mainly because of the influences of medical ethics and social desirability bias. Their preferences for SDM were not significantly correlated with their evaluations of DPR (P > 0.05). Physicians with different evaluations of DPR (good, poor, and strained) all had similar preferences for SDM (42.6, 56.4, and 42.9%), with no significant difference (P > 0.05). There was no correlation between physicians' evaluations of DPR and their preferences for SDM. Physicians' evaluations of poor DPR did not affect their preferences for SDM. This may be influenced by the medical ethics and social desirability bias.

Objective. A systematic review was conducted to compare the effectiveness and safety of fibroblast growth factor-2 (FGF2) and epidermal growth factor (EGF) for regeneration of the tympanic membrane (TM). Methods. The PubMed database was searched for relevant studies. Experimental and clinical studies reporting acute and chronic TM perforations in relation to two healing outcomes (success rate and closure time) and complications were selected. Results. A total of 47 studies were included. Five experimental studies showed closure rates of 55%–100% with FGF2 compared with 10%–62.5% in controls for acute perforations. Five experimental studies showed closure rates of 30.3%–100% with EGF and 3.6%–41% in controls for chronic perforations. Two experimental studies showed closure rates of 31.6% or 85.7% with FGF2 and 15.8% or 100% with EGF. Nine clinical studies of acute large perforations showed closure rates of 91.4%–100% with FGF2 or EGF. Two clinical studies showed similar closure rates between groups treated with FGF2 and EGF. Seven clinical studies showed closure rates of 88.9%–100% within 3 months and 58%–66% within 12 months using FGF2 in repair of chronic perforations, but only one study showed a significantly higher closure rate in the saline group compared with the FGF2 group (71.4% vs. 57.5%, respectively, P = 0.547 ). In addition, three experimental studies showed no ototoxicity associated with FGF2 or EGF. No middle ear cholesteatoma or epithelial pearls were reported, except in one experimental study and one clinical study, respectively. Conclusions. FGF2 and EGF showed good effects and reliable safety for the regeneration of TM. In addition, EGF was better for the regeneration of acute perforations, while FGF2 combined with biological scaffolds was superior to EGF for chronic perforations, but was associated with high rates of reperforation over time. Further studies are required to determine whether EGF or FGF2 is better for TM regeneration.

Objectives This study was performed to evaluate the efficacy of microwave ablation (MWA) eustachian tuboplasty for the treatment of patients with retracted tympanic membrane (TM) due to eustachian tube dysfunction (ETD). Methods This was a prospective study of 20 patients with ETD (middle ear atelectasis) who underwent MWA eustachian tuboplasty. Outcomes included the ability to perform a Valsalva maneuver, audiometry results, tympanometry results, ETD Questionnaire (ETDQ-7) score, and TM status. Results Eighteen patients (18 ears) were included in this study. There were statistically and clinically significant improvements in the mean ETDQ-7 score at 6 months postoperatively (change in mean score of 16.7 ± 3.6, P P Type A tympanogram was obtained in 27.8% of patients (5/18) at 6 months postoperatively, and in 77.7% at 30 months postoperatively. A Valsalva maneuver was possible in 72.2% of patients at 6 months postoperatively and in 88.9% of patients at 30 months postoperatively. In addition, the ears of 13 patients (72.2%) showed both normal tympanograms and TM at 30 months postoperatively. Interestingly, 38.5% of patients (5/13) exhibited complete sclerosis of the pars tensa. None of the patients experienced severe MWA-related complications during follow-up. Conclusions MWA eustachian tuboplasty is a feasible alternative to conventional tuboplasty, and can improve subjective and objective outcomes in patients with ETD for up to 30 months following treatment. In addition, this study showed that the extent of sclerotic plaque increased over time, whereas the extents of atrophy and tensa retraction decreased following tuboplasty in most patients. Graphical abstract

The prognostic value of quantitative assessments of the number of retrieved lymph nodes (RLNs) in gastric cancer (GC) patients needs further study.To discuss how to obtain a more accurate count of metastatic lymph nodes (MLNs) based on RLNs in different pT stages and then to evaluate patient prognosis.This study retrospectively analyzed patients who underwent GC radical surgery and D2/D2+ LN dissection at the Cancer Hospital of Harbin Medical University from January 2011 to May 2017. Locally weighted smoothing was used to analyze the relationship between RLNs and the number of MLNs. Restricted cubic splines were used to analyze the relationship between RLNs and hazard ratios (HRs), and X-tile was used to determine the optimal cutoff value for RLNs. Patient survival was analyzed with the Kaplan-Meier method and log-rank test. Finally, HRs and 95% confidence intervals were calculated using Cox proportional hazards models to analyze independent risk factors associated with patient outcomes.A total of 4968 patients were included in the training cohort, and 11154 patients were included in the validation cohort. The smooth curve showed that the number of MLNs increased with an increasing number of RLNs, and a nonlinear relationship between RLNs and HRs was observed. X-tile analysis showed that the optimal number of RLNs for pT1-pT4 stage GC patients was 26, 31, 39, and 45, respectively. A greater number of RLNs can reduce the risk of death in patients with pT1, pT2, and pT4 stage cancers but may not reduce the risk of death in patients with pT3 stage cancer. Multivariate analysis showed that RLNs were an independent risk factor associated with the prognosis of patients with pT1-pT4 stage cancer (A greater number of RLNs may not benefit the survival of patients with pT3 stage disease but can benefit the survival of patients with pT1, pT2, and pT4 stage disease. For the pT1, pT2, and pT4 stages, it is recommended to retrieve 26, 31 and 45 LNs, respectively.

Nitidine chloride (NC) is a standard active component from the traditional Chinese medicine Zanthoxylum nitidum (Roxb.) DC. (ZN). NC has shown a variety of pharmacological activities including anti-tumor activity. As a number of anti-tumor drugs cause cardiotoxicity, herein we investigated whether NC exerted a cardiotoxic effect and the underlying mechanism. Aqueous extract of ZN (ZNE) was intraperitoneally injected into rats, while NC was injected into beagles and mice once daily for 4 weeks. Cardiac function was assessed using echocardiography. We showed that both ZNE administered in rats and NC administered in mice induced dose-dependent cardiac hypertrophy and dysfunction, whereas administration of NC at the middle and high dose caused death in Beagles. Consistently, we observed a reduction of cardiac autophagy levels in NC-treated mice and neonatal mouse cardiomyocytes. Furthermore, we demonstrated that autophagy-related 4B cysteine peptidase (ATG4B) may be a potential target of NC, since overexpression of ATG4B reversed the cardiac hypertrophy and reduced autophagy levels observed in NC-treated mice. We conclude that NC induces cardiac hypertrophy via ATG4B-mediated downregulation of autophagy in mice. Thus, this study provides guidance for the safe clinical application of ZN and the use of NC as an anti-tumor drug.

Interleukin (IL)-1β is a culprit of adipose tissue inflammation, which in turn causes systematic inflammation and insulin resistance in obese individuals. IL-1β is mainly produced in monocytes and macrophages and marginally in adipocytes, through cleavage of the inactive pro-IL-1β precursor by caspase-1, which is activated via the NLRP3 inflammasome complex. The nuclear factor-κB (NF-κB) transcription factor is the master regulator of inflammatory responses. Brindle berry (Garcinia cambogia) has been widely used as health products for treating obesity and related metabolic disorders, but its active principles remain unclear. We previously found a series of polyisoprenylated benzophenones from brindle berry with anti-inflammatory activities. In this study we investigated whether 14-deoxygarcinol (DOG), a major polyisoprenylated benzophenone from brindle berry, alleviated adipose tissue inflammation and insulin sensitivity in high-fat diet fed mice. The mice were administered DOG (2.5, 5 mg · kg

Aim. To investigate the protective effects and possible mechanisms of action of resina draconis (RD) on acute liver injury and liver regeneration after 2/3 partial hepatectomy (PH) in mice. Methods. 2/3 PH was used to induce acute liver injury. Mice were divided into three groups: sham, vehicle + 2/3 PH, and RD + 2/3 PH. Resina draconis was administered intragastrically after 2/3 PH into the RD + 2/3 PH group, and the same volume of vehicle (1% sodium carboxymethyl cellulose) was injected into the vehicle + 2/3 PH group and sham group mice. The index of liver to body weight (ILBW) and proliferating cell nuclear antigen (PCNA) were assayed to evaluate liver regeneration. Blood and liver tissues were collected for serological and western blotting analysis. Results. Resina draconis protected against 2/3 PH-induced acute severe liver injury and promoted liver regeneration as shown by significantly increased ILBW compared with that of controls. 2/3 PH increased serum AST and ALT levels, which were significantly decreased by RD treatment, while 2/3 PH decreased serum TP and ALB, which were increased by RD treatment. In the RD + 2/3 PH group, PCNA expression was significantly increased compared with the 2/3 PH group. Further, hepatocyte growth factor (HGF), TNFα, and EGFR levels were increased in the RD group at postoperative days 2 and 4 compared with the those in the 2/3 PH group. Conclusion. Our results suggest that RD ameliorates acute hepatic injury and promotes liver cell proliferation, liver weight restoration, and liver function after 2/3 PH, probably via HGF, TNFα, and EGFR signaling.

Long noncoding RNAs (lncRNAs) are closely associated with the initiation, progression, metastasis, and recurrence of hepatocellular carcinoma (HCC). They could therefore serve as markers for the early diagnosis and for the prognosis of HCC patients.This was an observational prospective cohort study. A total of 101 participants were included, comprising patients with HCC (n = 61), liver cirrhosis (LC) (n = 20), or healthy controls (HC) (n = 20). The baseline characteristics of participants in each group were compared. Serum levels of the lncRNAs HOTAIR, BRM and ICR were determined in each group by reverse transcription and quantitative real-time polymerase chain reaction (qRT-PCR). Correlations between the serum levels of the three lncRNAs and multiple clinical parameters were analysed. The receiver operating characteristic (ROC) curve was used to assess the diagnostic potential for HCC of each lncRNA individually, or in combination with AFP. Multivariate Cox regression analysis was used to evaluate the accuracy of these lncRNAs for predicting the outcome and survival of HCC patients.The serum levels of HOTAIR, BRM and ICR were significantly higher in HCC patients compared to LC patients and healthy subjects. The HOTAIR level was positively correlated to tumour-node metastasis (TNM), Barcelona Clinic Liver Cancer (BCLC) stage, extrahepatic metastasis, vascular invasion, portal vein tumour thrombus (PVTT), and tumour size. The BRM level was positively associated with TNM stage, BCLC stage, vascular invasion, PVTT, and tumour size, while the ICR level was positively correlated with PVTT. A combination of the three lncRNAs and AFP showed the highest diagnostic accuracy for HCC, with an AUC of 0.998, sensitivity of 98.4%, and specificity of 100.0%. This combination showed a better diagnostic accuracy than the individual lncRNAs or AFP alone. Serum levels of the HOTAIR and ICR lncRNAs decreased significantly following surgery.Serum levels of the HOTAIR, BRM and ICR lncRNAs are potential prognostic markers for HCC. Upregulation of HOTAIR, BRM and ICR may facilitate early diagnosis and indicate poor prognosis for HCC. These lncRNAs could potentially serve as therapeutic targets for HCC. Combination of the three lncRNAs with AFP may increase the diagnostic accuracy for HCC. Further studies in larger cohorts of patients are needed to validate these findings.

Purpose Diabetic cardiomyopathy (DCM), a common complication of diabetes mellitus and is characterized by myocardial hypertrophy and myocardial fibrosis. Pyrroloquinoline quinone (PQQ), a natural nutrient, exerts strong protection against various myocardial diseases. Pyroptosis, a type of inflammation-related programmed cell death, is vital to the development of DCM. However, the protective effects of PQQ against DCM and the associated mechanisms are not clear. This study aimed to investigate whether PQQ protected against DCM and to determine the underlying molecular mechanism. Methods Diabetes was induced in mice by intraperitoneal injection of streptozotocin, after which the mice were administered PQQ orally (10, 20, or 40 mg/kg body weight/day) for 12 weeks. AC16 human myocardial cells were divided into the following groups and treated accordingly: control (5.5 mmol/L glucose), high glucose (35 mmol/L glucose), and HG + PQQ groups (1 and 10 nmol/L PQQ). Cells were treated for 24 h. Results PQQ reduced myocardial hypertrophy and the area of myocardial fibrosis, which was accompanied by an increase in antioxidant function and a decrease in inflammatory cytokine levels. Moreover, myocardial hypertrophy—(ANP and BNP), myocardial fibrosis—(collagen I and TGF-β1), and pyroptosis-related protein levels decreased in the PQQ treatment groups. Furthermore, PQQ abolished mitochondrial dysfunction and the activation of NF-κB/IκB, and decreased NLRP3 inflammation-mediated pyroptosis in AC16 cells under high-glucose conditions. Conclusion PQQ improved DCM in diabetic mice by inhibiting NF-κB/NLRP3 inflammasome-mediated cell pyroptosis. Long-term dietary supplementation with PQQ may be greatly beneficial for the treatment of DCM. Graphical abstract Diagram of the underlying mechanism of the effects of PQQ on DCM. PQQ inhibits ROS generation and NF-κB activation, which stimulates activation of the NLRP3 inflammasome and regulates the expression of caspase-1, IL-1β, and IL-18. The up-regulated inflammatory cytokines trigger myocardial hypertrophy and cardiac fibrosis and promote the pathological process of DCM.

Introduction: Most of traumatic tympanic membrane perforations have inverted or everted edges, however, the effects of inverted and everted edges on the spontaneous healing of the eardrum remain controversial. Objective: We investigated the influence of inverted or everted edges on the spontaneous healing of traumatic tympanic membrane perforations. Methods: The clinical records of patients with a traumatic tympanic membrane perforations who met the study criteria were retrieved and categorized into two groups, based on whether the eardrum was inverted or everted. The features along the edge of each inverted or everted eardrum were described using 30° and 70° endoscopes. Results: In total, 196 patients (196 ears) met the inclusion criteria; of these, 148 had inverted or everted eardrums while 48 did not. Of the 148 patients with inverted or everted eardrums, the perforation edges were everted in 77 patients, inverted in 44 patients, drooping in 17 patients, and both inverted and everted in 10 patients. The perforation shape was triangular in 18.9% of patients, sector-shaped in 11.5%, kidney-shaped in 14.2%, ovoid in 20.3%, and irregularly shaped in 35.1% of patients. The difference was not significant between the with and without inverted/everted eardrum edges groups in terms of the closure rate or closure time. Similarly, the difference was not significant between the with and without edge approximation groups in terms of the closure rate or closure time at the end of the 12-month follow-up period. Conclusion: This study suggests that endoscopic inspection can clearly identify inverted/everted eardrum edges using 30° and 70° endoscopes. The edge is glossy in inverted/everted eardrums, whereas the edge is rough and irregular in non-inverted/everted cases. The inverted/everted eardrums gradually became necrotic, but this did not affect the healing process. Additionally, edge approximation did not improve the healing outcome of traumatic tympanic membrane perforations. Resumo: Introdução: A maioria das perfurações de membrana timpânica traumáticas apresenta bordas invertidas ou evertidas; no entanto, os efeitos dessas configurações sobre a cicatrização espontânea do tímpano continuam a ser uma questão controversa. Objetivo: Investigar a influência de bordas invertidas ou evertidas sobre a cicatrização espontânea de perfurações traumáticas de membrana timpânica. Método: Os prontuários clínicos de pacientes com perfuração traumática de membrana timpânica que preencheram os critérios do estudo foram recuperados e categorizados em dois grupos, baseados na configuração invertida ou evertida das bordas da membrana timpânica. As características de configuração da borda de cada membrana foram descritas com o uso de endoscópios de 30° e 70°. Resultados: No total, 196 pacientes (196 orelhas) preencheram os critérios de inclusão; desses, 148 apresentavam bordas de membranas timpânicas invertidas ou evertidas, enquanto 48 não. Dos 148 pacientes, as bordas da perfuração estavam evertidas em 77 pacientes, invertidas em 44 pacientes, caídas em 17 pacientes e ambas invertidas e evertidas em 10 pacientes. O formato da perfuração era triangular em 18,9% dos pacientes, em forma de fatia de pizza em 11,5%, em forma de rim em 14,2%, ovoide em 20,3% e de forma irregular em 35,1% dos pacientes. A diferença não foi significante entre os grupos com e sem membrana timpânica invertida/evertida em termos de taxa ou tempo de fechamento. Da mesma forma, a diferença não foi significativa entre os grupos com e sem aproximação das bordas em termos de taxa de fechamento ou tempo de fechamento no fim do período de seguimento de 12 meses. Conclusões: Este estudo sugere que a avaliação com endoscópios de 30° e 70° pode identificar claramente as bordas invertidas/evertidas das perfurações de membranas timpânicas. A borda da perfuração timpânica em casos invertidos/evertidos é brilhante, enquanto a borda é áspera e irregular em casos não invertidos/evertidos. O rebordo timpânico invertido/evertido gradualmente torna-se necrótico, mas isso não afetou o processo de cicatrização. Além disso, a aproximação das bordas não melhorou o resultado da cicatrização. Keywords: Traumatic, Tympanic membrane perforation, Edge approximation, Spontaneous healing, Palavras-chave: Traumática, Perfuração da membrana timpânica, Aproximação da borda, Cicatrização espontânea

Background/objective. Most researchers consider that basic fibroblast growth factor (bFGF) facilitates the repair of chronic tympanic membrane (TM) perforations in chronic otitis media (COM). However, the addition of biological materials affects bFGF levels. This study was performed to compare the effects of bFGF alone and myringoplasty for the repair of chronic perforations. Study design. A prospective cohort control study. Materials and methods. Patients with chronic central perforations who met the inclusion criteria were divided into two groups, i.e., bFGF alone group and underlay myringoplasty group. In the bFGF alone group, the epithelium was removed circumferentially around the perforation edge to create fresh edges. Approximately, 0.1–0.15 mL of bFGF solution was applied twice daily for 3 months to the TM, to keep the edges moist without a scaffold. In the myringoplasty group, the perichondrium graft was placed underneath the TM remnant by endoscopy. TM closure and hearing outcomes were evaluated at 12 weeks after surgery or at the end of bFGF treatment. Results. A total of 29 patients consisting 13 in the bFGF alone group and 16 in the myringoplasty group were finally included in the analysis. Of the 13 patients in the bFGF alone group, the perforations were small in 6 and medium in 7; the etiology was secondary to COM in 11 and to trauma in 2. One patient with an unhealed perforation continued bFGF treatment until 6 months, while the others stopped at 3 months. Of the seven medium-sized perforations, none of the five COM perforations closed, while the two traumatic perforations achieved complete closure within 2 and 4 weeks, respectively. The successful closure rate was 28.6% (2/7). Successful closure was achieved in 66.7% (4/6) of the six small perforations with COM, with a mean closure time of 4.75 weeks. Of the 16 patients in the myringoplasty group, all perforations were medium-sized and were secondary to COM in 15 cases and traumatic in 1 case; all achieved complete closure. Conclusions. bFGF alone facilitated the repair of chronic traumatic perforations and small perforations with COM, but not medium-sized perforations with COM. These observations indicated that the regenerative conditions of traumatic perforations are better than those of COM perforations when using bFGF alone, and that graft materials could play a critical role in the regeneration of larger-sized chronic perforations with COM.

NLRP3 (Nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3) inflammasome-mediated cardiomyocytes pyroptosis plays a crucial part in progression of acute myocardial infarction (MI). GDF11 (Growth Differentiation Factor 11) has been reported to generate cytoprotective effects in phylogenesis and multiple diseases, but the mechanism that GDF11 contributes to cardioprotection of MI and cardiomyocytes pyroptosis remains poorly understood. In our study, we first determined that GDF11 was abnormally downregulated in the heart tissue of MI mice and hypoxic cardiomyocytes. Moreover, AAV9-GDF11 markedly alleviated heart function in MI mice. Meanwhile, GDF11 overexpression also decreased the pyroptosis of hypoxic cardiomyocytes. PROMO and JASPAR prediction software found that transcription factor HOXA3 was predicted as an important regulator of NLRP3, and was confirmed by ChIP assay. Further analysis identifying GDF11 promoted the Smad2/3 pathway resulted in HOXA3 overexpression. Taken together, our study implies that GDF11 prevents cardiomyocytes pyroptosis via HOXA3/NLRP3 signaling pathway in MI mice.

Vibrio vulnificus (V. vulnificus) is an estuarine bacterium that is capable of causing rapidly fatal infection in humans. Proper polarization and bactericidal activity of macrophages play essential roles in defending against invading pathogens. How macrophages limit V. vulnificus infection remains not well understood. Here we report that tuberous sclerosis complex 1 (TSC1) is crucial for the regulation of V. vulnificus-induced macrophage polarization, bacterial clearance, and cell death. Mice with myeloid-specific deletion of TSC1 exhibit a significant reduction of survival time after V. vulnificus infection. V. vulnificus infection induces both M1 and M2 polarization. However, TSC1 deficient macrophages show enhanced M1 response to V. vulnificus infection. Interestedly, the absence of TSC1 in myeloid cells results in impaired bacterial clearance both in vivo and in vitro after V. vulnificus infection. Inhibition of the mammalian target of rapamycin (mTOR) activity significantly reverses V. vulnificus-induced hypersensitive M1 response and resistant bactericidal activity both in wild-type and TSC1-deficient macrophages. Moreover, V. vulnificus infection causes cell death of macrophages, possibly contributes to defective of bacterial clearance, which also exhibits in a mTORC1-dependent manner. These findings highlight an essential role for the TSC1-mTOR signaling in the regulation of innate immunity against V. vulnificus infection.

In this paper, we have explored non-gravitational interaction dark energy model between dark energy and cold dark matter (CDM). The main purpose of this work is to explore the deviations from &Lambda, C D M and to distinguish the evolution trajectory of the interaction dark energy model with different parameters. Six forms of interaction were focused on. We have analyzed the deceleration parameters of the coupled model and explored the theoretical models through s t a t e f i n d e r h i e r a r c h y and the O m diagnostic. We have considered that the Equation of State (EoS) parameter w and parameter &xi, take different values on the interaction dark energy model respectively and keep another parameter unchanged. It was found that q ( z ) is the worst of the four diagnoses. O m , S 3 ( 1 ) and S 4 ( 1 ) are good tools to distinguish the interaction dark energy model from &Lambda, C D M . S 3 ( 1 ) is a better diagnostic tool when the state parameter w changes and the coupling parameter &xi, is fixed, while S 4 ( 1 ) works better when the coupling parameter &xi, changes and the state parameter w is fixed.

The brown planthopper (BPH), Nilaparvata lugens, is a serious migratory rice pest, which is distributed in the broad area of the tropical and temperate Asian-Pacific region. However, we know little about key aspects regarding its evolution such as how they diverged and dispersed worldwide. By resequencing and analyzing 358 BPH genomes from 92 populations across the world, we uncover the genetic relationships among their worldwide populations and the history of their global dispersal. We recovered five genetic groups representing the major population structures. Of these, Australian BPHs were shown large genetic divergence with Asian BPHs; two distinct groups have formed in South and Southeast/East Asia that show strong genetic admixture in the southwest border regions of China and west Thailand with Myanmar; two local populations in Bangladesh and Fujian province of China, respectively, unexpectedly separated with surrounding populations. We also find the genetic similarity and closely phylogenetic relationships between majority of East Asian BPHs and Indo-china peninsula BPHs, indicating that Southeast Asia mainland is the major insect sources and overwintering sites for East Asia. Our study provides important molecular evidence to address BPH evolution and other key aspects of its biology such as insecticides resistance and rice varieties virulence.

Vitellogenin (Vg) is precursor of vitellin. Here, we identified a Vg (NlVg) and two Vg-likes (NlVg-like1 and NlVg-like2) in the brown planthopper, Nilaparvata lugens. Phylogenetic analyses showed that NlVg-like1 and NlVg-like2 are not clustered with the conventional insect Vgs associated with vitellogenesis. Temporo-spatial expression analyses showed that the NlVg and NlVg-like2 transcript levels increased significantly 24 h after emergence and were primarily expressed in female adults. However, NlVg-like1 was expressed during all stages, and in both genders. Tissue-specific analyses showed that all three genes were most highly expressed in the fat body. The injection of double-stranded RNA targeting NlVg showed that NlVg is essential not only for oocyte development but also for nymph development. The knockdown of NlVg-like1 in female adults resulted in failure to hatch or death before eggshell emergence in 18% of offspring embryos, suggesting that NlVg-like1 plays an important role during late embryogenesis. Approximately 65% of eggs laid by females that were treated with double-stranded RNA targeting NlVg-like2 failed to hatch, indicating that NlVg-like2 plays a role in nutrition absorption during oocyte, or embryonic development. Our results illustrate the structural and functional differences among the Vg and Vg-like genes and provide potential targets for RNA-interference-based insect pest management strategies.

Mucins play a variety of roles; for example, in vertebrates, mucins lubricate epithelial surfaces and protect tissue from physical and biological damage, however, knowledge of insect mucins is limited. Here, we identified an eggshell-related mucin-like protein, NlESMuc, in the brown planthopper (BPH), Nilaparvata lugens. NlESMuc was specifically expressed in the follicular cells from the egg chambers of the ovarioles. RNA interference (RNAi) was used to perform functional analysis of NlESMuc. Adult female BPH with NlESMuc knockdown had significantly reduced fecundity, including more difficult oviposition, lower egg production, and eggs that could not hatch. Scanning electron microscopy showed that, in NlESMuc knocked-down BPH, the ultrastructure of the eggshells of fully developed oocytes was loose, and the cross-section showed many small droplets of about 0.1-μm diameter. Based on the results, it is concluded that NlESMuc is an eggshell-related protein and essential for normal oviposition. Our findings help to provide new targets for pesticide design and RNAi-based BPH control and will also provide new insights into insect eggshells and insect mucins.

Mucins play a variety of roles; for example, in vertebrates, mucins lubricate epithelial surfaces and protect tissue from physical and biological damage, however, knowledge of insect mucins is limited. Here, we identified an eggshell-related mucin-like protein, NlESMuc, in the brown planthopper (BPH), Nilaparvata lugens. NlESMuc was specifically expressed in the follicular cells from the egg chambers of the ovarioles. RNA interference (RNAi) was used to perform functional analysis of NlESMuc. Adult female BPH with NlESMuc knockdown had significantly reduced fecundity, including more difficult oviposition, lower egg production, and eggs that could not hatch. Scanning electron microscopy showed that, in NlESMuc knocked-down BPH, the ultrastructure of the eggshells of fully developed oocytes was loose, and the cross-section showed many small droplets of about 0.1-μm diameter. Based on the results, it is concluded that NlESMuc is an eggshell-related protein and essential for normal oviposition. Our findings help to provide new targets for pesticide design and RNAi-based BPH control and will also provide new insights into insect eggshells and insect mucins.

In situ grown zerovalent nanoiron/magnetite on sponge-like carbon matrix (nZVI/Fe3O4@C) has been evaluated for the removal of toxic hexavalent chromium (Cr(VI)) from polluted water. This material is synthesized by calcination of the epoxide group-functionalized polystyrene (FPS) as the carbon source under a mixture of 5% hydrogen/argon (v/v) atmosphere. The nZVI/Fe3O4@C demonstrates a unique capability to remove Cr(VI) from polluted water over a wide pH range, and the optimal pH value for Cr(VI) removal is 5.0 at 298 K. In comparison, only Fe3O4@C is formed when the as-received PS is used as the carbon source under the same atmosphere conditions and exhibits a poor Cr(VI) removal performance (the removal percentage is around 50% relative to nZVI/Fe3O4@C). Various factors influencing the Cr(VI) removal efficiency, such as treatment time, initial Cr(VI) concentration and nZVI/Fe3O4@C dosage, have been systematically studied. The Cr(VI) removal mechanism is confirmed by X-ray photoelectron spectroscopy (XPS) and Raman tests. The results illustrate that the Cr(VI) is reduced to Cr(III) by nZVI with the simultaneous adsorption of Cr(III) via C–O–Fe bonds on nZVI/Fe3O4@C. The Cr(VI) removal kinetics is determined to follow pseudo-first-order behavior with calculated pseudo-first-order rate constants of 0.01582, 0.02555 and 0.03264 min−1 at 298, 308 and 318 K, respectively, at a pH of 5.0. The low value of the activation energy (28.621 kJ mol−1) indicates that the Cr(VI) reduction process on nZVI/Fe3O4@C is a fast process. The calculated thermodynamic parameters of this chemical reaction, including negative ΔG0, positive ΔH0 and positive ΔS0, suggest that the Cr(VI) reduction on nZVI/Fe3O4@C is spontaneous and endothermic, and more preferred at higher temperatures. Both the kinetics and thermodynamics show that the nZVI/Fe3O4@C is a promising material for highly fast and efficient removal of Cr(VI) from polluted water.

Hexavalent chromium (Cr(VI)) was chosen to serve as an oxidant to functionalize the surface of graphite. The effect of pH and concentration of Cr(VI) solution on the functionalization of graphite was systematically investigated by Raman spectroscopy, Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), and X-ray photoelectron spectroscopy (XPS). The results showed that the ether (C–O–C) functional groups were observed on the surface of graphite after being treated with pH = 1.0 solution with a Cr(VI) concentration of 1000 μg L−1 for 30 min. However, no obvious functional groups were observed on the graphite surface for the pH higher than 2.0 and the Cr(VI) concentrations higher than 2.0 mg L−1. The electrical conductivity of functionalized graphite by Cr(VI) was observed to be good, i.e., the same order of magnitude as that of the as-received graphite without a serious decrease. This work provides a new strategy to functionalize graphite for preparing multifunctional graphite nanocomposites.

Introduction: In the last decade, there has been an increasing use of biomaterial patches in the regeneration of traumatic tympanic membrane perforations. The major advantages of biomaterial patches are to provisionally restore the physiological function of the middle ear, thereby immediately improving ear symptoms, and act as a scaffold for epithelium migration. However, whether there are additional biological effects on eardrum regeneration is unclear for biological material patching in the clinic. Objective: This study evaluated the healing response for different repair patterns in human traumatic tympanic membrane perforations by endoscopic observation. Methods: In total, 114 patients with traumatic tympanic membrane perforations were allocated sequentially to two groups: the spontaneous healing group (n = 57) and Gelfoam patch-treated group (n = 57). The closure rate, closure time, and rate of otorrhea were compared between the groups at 3 months. Results: Ultimately, 107 patients were analyzed in the two groups (52 patients in the spontaneous healing group vs. 55 patients in the Gelfoam patch-treated group). The overall closure rate at the end of the 3 month follow-up period was 90.4% in the spontaneous healing group and 94.5% in the Gelfoam patch-treated group; the difference was not statistically significant (p > 0.05). However, the total average closure time was significantly different between the two groups (26.8 ± 9.1 days in the spontaneous healing group vs. 14.7 ± 9.1 days in the Gelfoam patch-treated group, p 0,05). No entanto, o tempo total médio de fechamento foi significativamente diferente entre os dois grupos (26,8 ± 9,1 dias no de cicatrização espontânea versus 14,7 ± 9,1 dias no tratado com esponja de Gelfoam, p

Expression of nuptial color is usually energetically costly, and is therefore regarded as an ‘honest signal’ to reflect mate quality. In order to choose a mate with high quality, both sexes may benefit from the ability to precisely evaluate their mates through optimizing visual systems which is in turn partially regulated by opsin gene modification. However, how terrestrial vertebrates regulate their color vision sensitivity is poorly studied. The green-spotted grass lizard Takydromus viridipunctatus is a sexually dimorphic lizard in which males exhibit prominent green lateral colors in the breeding season. In order to clarify relationships among male coloration, female preference, and chromatic visual sensitivity, we conducted testosterone manipulation with mate choice experiments, and evaluated the change of opsin gene expression from different testosterone treatments and different seasons. The results indicated that males with testosterone supplementation showed a significant increase in nuptial color coverage, and were preferred by females in mate choice experiments. By using quantitative PCR (qPCR), we also found that higher levels of testosterone may lead to an increase in rhodopsin-like 2 (rh2) and a decrease in long-wavelength sensitive (lws) gene expression in males, a pattern which was also observed in wild males undergoing maturation as they approached the breeding season. In contrast, females showed the opposite pattern, with increased lws and decreased rh2 expression in the breeding season. We suggest this alteration may facilitate the ability of male lizards to more effectively evaluate color cues, and also may provide females with the ability to more effectively evaluate the brightness of potential mates. Our findings suggest that both sexes of this chromatically dimorphic lizard regulate their opsin expression seasonally, which might play an important role in the evolution of nuptial coloration.

Significance The cuticle, mainly composed of chitin and cuticular proteins (CPs), is a multifunctional structure of arthropods. CPs usually account for >1% of the total insect proteins encoded in the genome. Why does an insect need so many different CPs? In this study, we use comprehensive large-scale technologies to study the full complement of CPs and their functions in the brown planthopper (BPH). A total of 32 of the 140 BPH CP genes are found to be essential for nymph/adult development, egg production, or embryo development; in addition, redundant and complementary functions of CPs are revealed., Cuticle, mainly composed of chitin and cuticular proteins (CPs), is a multifunctional structure of arthropods. CPs usually account for >1% of the total insect proteins. Why does an insect encode so many different CP genes in the genome? In this study, we use comprehensive large-scale technologies to study the full complement of CPs (i.e., the CP-ome) of the brown planthopper (BPH), Nilaparvata lugens, a major rice plant pest. Eight CP families (CPR, CPF, TWDL, CPLCP, CPG, CPAP1, CPAP3, and CPAPn) including 140 proteins in BPH, in which CPAPn is a CP family that we discovered. The CPG family that was considered to be restricted to the Lepidoptera has also been identified in BPH. As reported here, CPLCP family members are characterized by three conserved sequence motifs. In addition, we identified a testis protein family with a peritrophin A domain that we named TPAP. We authenticated the real existence of 106 proteins among the 140 CPs. RNA interference (RNAi) experiments were conducted against 135 CP genes in early- and late-instar nymphs and newly emerged female adults, demonstrating that 32 CPs were essential for BPH normal development or egg production. Combined RNAi experiments suggested redundant and complementary functions of the large number of CPs. Transcriptomic data revealed that the CP genes were expressed in a tissue-specific manner, and there were four clusters of developmental expression patterns. This study gives a comprehensive understanding of the roles of CPs in an insect cuticle.

Most animals are oviparous. However, the genes regulating egg shell formation remain not very clear. In this study, we found that Nilaparvata lugens Forkhead box transcription factor L2 ( Nl FoxL2) directly activated follicle cell protein 3C ( NlFcp3C ) to regulate chorion formation. NlFoxL2 and NlFcp3C had a similar expression pattern, both highly expressed in the follicular cells of female adults. Knockdown of NlFoxL2 or NlFcp3C also resulted in the same phenotypes: obesity and female infertility. RNA interference (RNAi) results suggested that NlFcp3C is a downstream gene of NlFoxL2 . Furthermore, transient expression showed that Nl FoxL2 could directly activate the NlFcp3C promoter. These results suggest that NlFcp3C is a direct target gene of Nl FoxL2. Depletion of NlFoxL2 or NlFcp3C prevented normal chorion formation. Our results first revealed the functions of Fcp3C and FoxL2 in regulation of oocyte maturation in an oviparous animal.

Let M be a simple 3-manifold, and F be a component of ∂M of genus at least 2. Let α and β be separating slopes on F. Let M ( α ) (resp. M ( β ) ) be the manifold obtained by adding a 2-handle along α (resp. β). If M ( α ) and M ( β ) are ∂-reducible, then the minimal geometric intersection number of α and β is at most 8.

A baculovirus, named BomaNPV S2, was isolated from a diseased larva of the wild silkworm, Bombyx mandarina. Notably, BomaNPV S2 exhibited a distinguishing feature in that its host range covered that of both Bombyx mori nucleopolyhedrosis virus (BmNPV) and Autographa californica multiple nucleopolyhedrovirus (AcMNPV) in cultured cells. It could replicate in cells of B. mori (Bm5 and BmN), Spodoptera frugiperda (Sf9) and Trichoplusia ni (Tn-5B1-4). However, occlusion-derived virions of BomaNPV S2 in B. mori cells contained only a single nucleocapsid, whereas they contained multiple nucleocapsids in Tn-5B1-4 cells. The complete genome sequence of BomaNPV S2, including predicted ORFs, was determined and compared with the genome sequence of its close relatives. The comparison results showed that most of the BomaNPV S2 genome sequence was shared with BmNPV (BmNPV T3) or BomaNPV S1, but several regions seemed more similar to regions of AcMNPV. This observation might explain why BomaNPV S2 covers the host ranges of BmNPV and AcMNPV. Further recombinant virus infection experiments demonstrated that GP64 plays an important role in BomaNPV S2 host-range determination.

Background: Rosemary (Rosmarinus offcinsalis L) has a liver protection function under various conditions of liver damage. Rosmarinic acid, one of the pharmacological constituents of rosemary, exhibited protective effects against organ injury, including acute liver injury. Hypothesis: We hypothesize that RA stimulates liver regeneration. Study Design: In the present study, we investigated the effects and mechanism of RA administration on liver regeneration using partial hepatectomy (PH), a well-validated liver regeneration model in mice. Methods: We use a 2/3 partial hepatectomy (PH) model to induce liver regeneration. RA was administered prior to and simultaneously with PH. The regeneration process was estimated by the index of the liver to body weight (ILBW) and the expression of proliferating cell nuclear antigen (PCNA) and liver transaminases. Results: The administration of rosmarinic acid stimulated hepatocyte proliferation based on activation of the mTOR/S6K pathway. Rosmarinic acid treatment also rescued impaired liver function due to PH. Conclusion: These data demonstrate that RA is potentially useful to promote liver regeneration.

The electrophoretic behavior of a non-conducting, Newtonian drop of low surface potential normal to a plane is investigated theoretically under the conditions of weak applied electric field and arbitrary thickness of double layer. The governing equations and the associated boundary conditions expressed in terms of bipolar spherical coordinates are solved by an orthogonal collocation method. In general, the thinner the double layer surrounding a drop and/or the longer its distance from a planar surface, the larger its mobility, and if a drop is sufficiently close to a plane, its mobility may change sign. These results are similar to the case of a rigid particle. The mobility of a drop decreases with the increase in the ratio (viscosity of drop fluid/viscosity of dispersion medium). Under the conditions assumed, a drop can be treated as a rigid sphere if the viscosity ratio exceeds about 100, and as a bubble if it is smaller than about 0.01.

Background The brown planthopper, Nilaparvata lugens, the most destructive pest of rice, is a typical monophagous herbivore that feeds exclusively on rice sap, which migrates over long distances. Outbreaks of it have re-occurred approximately every three years in Asia. It has also been used as a model system for ecological studies and for developing effective pest management. To better understand how a monophagous sap-sucking arthropod herbivore has adapted to its exclusive host selection and to provide insights to improve pest control, we analyzed the genomes of the brown planthopper and its two endosymbionts. Results We describe the 1.14 gigabase planthopper draft genome and the genomes of two microbial endosymbionts that permit the planthopper to forage exclusively on rice fields. Only 40.8% of the 27,571 identified Nilaparvata protein coding genes have detectable shared homology with the proteomes of the other 14 arthropods included in this study, reflecting large-scale gene losses including in evolutionarily conserved gene families and biochemical pathways. These unique genomic features are functionally associated with the animal’s exclusive plant host selection. Genes missing from the insect in conserved biochemical pathways that are essential for its survival on the nutritionally imbalanced sap diet are present in the genomes of its microbial endosymbionts, which have evolved to complement the mutualistic nutritional needs of the host. Conclusions Our study reveals a series of complex adaptations of the brown planthopper involving a variety of biological processes, that result in its highly destructive impact on the exclusive host rice. All these findings highlight potential directions for effective pest control of the planthopper. Electronic supplementary material The online version of this article (doi:10.1186/s13059-014-0521-0) contains supplementary material, which is available to authorized users.

The boundary effect on the dynamic electrophoretic behavior of a charged entity is examined by considering a sphere in a spherical cavity. The present study extends previous analysis to the case of an arbitrary level of electrical potential where the effect of double-layer distortion can be significant. The governing equations are solved numerically based on a pseudo-spectral method, which is found to be sufficient in solving the corresponding electrophoresis problem when a static electric field is applied. The result of numerical simulation reveals that as the size of a cavity decreases, both the magnitude of the mobility and the inertial force acting on a particle decrease accordingly. Also, while the distortion of the ionic cloud should not be ignored, in general, when the surface potential of a particle is high, its influence on the magnitude and on the phase angle of the mobility is alleviated by the presence of the cavity.