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The poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC)-modified, silicone hydrogel, contact lens (CL) material lehfilcon A has previously been demonstrated to have a lubricious, antifouling and ultra-soft surface. This study provides confirmatory identification of the outer polymer structures on this CL surface as branched PMPC structures. It further aims to understand their role in providing enhanced tribological performance via fluid confinement. A combination of scanning transmission electron microscopy and atomic force microscopy infrared spectroscopy has been used to achieve both morphological and chemical confirmation of branched PMPC structures resembling the polysaccharide species present on the surface of the cornea. Measurements of the fluid-confinement behaviour of this layer, by means of nanoindentation experiments, show it to resist squeeze-out of the interstitial fluid, thereby boosting lubrication by virtue of a fluid-load-support mechanism. Tribological testing of CLs showed this effective lubrication to be maintained after one month of daily wearing., Competing Interests: We declare we have no competing interests., (© 2024 The Author(s).)

Mycorrhizal associations are key mutualisms that shape the structure of forest communities and multiple ecosystem functions. However, we lack a framework for predicting the varying dominance of distinct mycorrhizal associations in an integrated proxy of multifunctionality across ecosystems. Here, we used the datasets containing diversity of mycorrhizal associations and 18 ecosystem processes related to supporting, provisioning, and regulating services to examine how the dominance of ectomycorrhiza (EcM) associations affects ecosystem multifunctionality in subtropical mountain forests in Southwest China. Meanwhile, we synthesized the prevalence of EcM-dominant effects on ecosystem functioning in forest biomes. Our results demonstrated that elevation significantly modified the distributions of EcM trees and fungal dominance, which in turn influenced multiple functions simultaneously. Multifunctionality increased with increasing proportion of EcM associations, supporting the ectomycorrhizal-dominance hypothesis. Meanwhile, we observed that the impacts of EcM dominance on individual ecosystem functions exhibited different relationships among forest biomes. Our findings highlight the importance of ectomycorrhizal dominance in regulating multifunctionality in subtropical forests. However, this ectomycorrhizal feedback in shaping ecosystem functions cannot necessarily be generalized across forests. Therefore, we argue that the predictions for ecosystem multifunctionality in response to the shifts of mycorrhizal composition could vary across space and time., (© 2024 The Author(s). New Phytologist © 2024 New Phytologist Foundation.)

The viral genome titer is a crucial indicator for the clinical dosing, manufacturing, and analytical testing of recombinant adeno-associated virus (rAAV) gene therapy products. Although quantitative PCR and digital PCR are the common methods used for quantifying the rAAV genome titer, they are limited by inadequate accuracy and robustness. The clustered regularly interspaced short palindromic repeat (CRISPR)-Cas12a biosensor is being increasingly used in virus detection; however, there is currently no report on its application in the titer determination of gene therapy products. In the present study, an amplification-free CRISPR-Cas12a assay was developed, optimized, and applied for rAAV genome titer determination. The assay demonstrated high precision and accuracy within the detection range of 4 × 10 9 and 10 11 vg/mL. No significant difference was observed between the Cas12a and qPCR assay results ( p  < 0.05, t test). Moreover, Cas12a exhibited similar activity on both single-stranded and double-stranded DNA substrates. Based on this characteristic, the titers of positive-sense and negative-sense strands were determined separately, which revealed a significant difference between their titers for an in-house reference AAV5-IN. This study presents the inaugural report of a Cas12a assay developed for the titer determination and composition analysis of the rAAV genome., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)

Thiram is a toxic fungicide extensively used for the management of pathogens in fruits. Although it is known that thiram degrades in plant tissues, the key enzymes involved in this process remain unexplored. In this study, we report that a tau class glutathione S-transferase (GST) from Carica papaya can degrade thiram. This enzyme was easily obtained by heterologous expression in Escherichia coli, showed low promiscuity toward other thiuram disulfides, and catalyzed thiram degradation under physiological reaction conditions. Site-directed mutagenesis indicated that G-site residue S67 shows a key influence for the enzymatic activity toward thiram, while mutation of residue S13, which reduced the GSH oxidase activity, did not significantly affect the thiram-degrading activity. The formation of dimethyl dithiocarbamate, which was subsequently converted into carbon disulfide, and dimethyl dithiocarbamoylsulfenic acid as the thiram degradation products suggested that thiram undergoes an alkaline hydrolysis that involves the rupture of the disulfide bond. Application of the GST selective inhibitor 4-chloro-7-nitro-2,1,3-benzoxadiazole reduced papaya peel thiram-degrading activity by 95%, indicating that this is the main degradation route of thiram in papaya. GST from Carica papaya also catalyzed the degradation of the fungicides chlorothalonil and thiabendazole, with residue S67 showing again a key influence for the enzymatic activity. These results fill an important knowledge gap in understanding the catalytic promiscuity of plant GSTs and reveal new insights into the fate and degradation products of thiram in fruits., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The fastest-growing microbe Vibrio natriegens is an excellent platform for bioproduction processes. Until now, this marine bacterium has not been examined for bioremediation applications, where the production of substantial amounts of biomass would be beneficial. V. natriegens can perform extracellular electron transfer (EET) to Fe(III) via a single porin-cytochrome circuit conserved in Vibrionaceae. Electroactive microbes capable of EET to Fe(III) usually also reduce toxic metals such as carcinogenic Cr(VI), which is converted to Cr(III), thus decreasing its toxicity and mobility. Here, the performance of V. natriegens was explored for the bioremediation of Cr(VI). At a density of 100 mg/mL, V. natriegens removed 5-20 mg/L Cr(VI) within 30 s and 100 mg/L Cr(VI) within 10 min. In comparison, the model bacterium Escherichia coli grown to a comparable cell density removed Cr(VI) 36 times slower. To eliminate Cr(VI), V. natriegens had to be metabolically active, and functional outer-membrane c-type cytochromes were required. At the end of the Cr(VI) removal process, V. natriegens had reduced all of it into Cr(III) while adsorbing more than half of the metallic ions. These results demonstrate that V. natriegens, with its fast metabolism, is a viable option for the rapid treatment of aqueous pollution with Cr., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This study aimed to investigate the effects of perfluorooctanesulfonic acid (PFOS) exposure on glucose-stimulated insulin secretion (GSIS) of rat insulinoma (INS-1) cells and the potential protective effects of procyanidins (PC). The effects of PFOS and/or PC on GSIS of INS-1 cells were investigated after 48 h of exposure (protein level: insulin; gene level: glucose transporter 2 (Glut2), glucokinase (Gck), and insulin). Subsequently, the effects of exposure on the intracellular reactive oxygen species (ROS) activity were measured. Compared to the control group, PFOS exposure (12.5, 25, and 50 μM) for 48 h had no significant effect on the viability of INS-1 cells. PFOS exposure (50 μM) could reduce the level of insulin secretion and reduce the relative mRNA expression levels of Glut2, Gck, and insulin. It is worth noting that PC could partially reverse the damaging effect caused by PFOS. Significantly, there was an increase in ROS after exposure to PFOS and a decline after PC intervention. PFOS could affect the normal physiological function of GSIS in INS-1 cells. PC, a plant natural product, could effectively alleviate the damage caused by PFOS by inhibiting ROS activity.

Objective: This study was aimed to investigate the role of non-neuronal cholinergic system (NNCS) in the early stage response of epithelial-mesenchymal transformation (EMT) related markers in human lung adenocarcinoma A549 cells induced by coal particles., Methods: A549 cells were exposed to different concentrations of GBW11110K, GBW11126D and exogenous acetylcholinesterase (AChE) (the exposure doses were determined according to the results of CCK-8 experiment, and the doses that had no significant effects on cell viability were selected) for 24 h. After exposure, the indexes of oxidative stress (SOD and MDA), inflammatory factors (IL-6 and TNF-α), EMT marker proteins (E-cadherin and vimentin), AChE enzymatic activity and mRNA expression levels of different types of acetylcholine receptors ( CHRM3, CHRM5, CHRNA5, CHRNA7, CHRNA9 and CHRNB2 ) were determined., Results: GBW11110K and GBW11126D exposure could lead to the following injury effects: the levels of oxidative stress and inflammatory factors changed to a certain extent (SOD decreased gradually, while MDA, IL-6 and TNF-α increased). The protein level of E-cadherin decreased while the vimentin level increased ( P < 0.05), suggesting the occurrence of EMT. The AChE enzymatic activity decreased gradually. The expression of acetylcholine receptor mRNA changed as follows (GBW11110K/GBW11126D: CHRM3 (↑↑), CHRM5 (↓↓), CHRNA5 (↓↓), CHRNA7 (↓↓), CHRNA9 (- ↑), CHRNB2 (- -). The addition of exogenous AChE recombinant protein could antagonize the damage effects caused by the coal particles to a certain extent., Conclusion: The coal particle exposure could induce the change of oxidative stress response, inflammatory response and EMT related markers, down-regulate the AChE enzymatic activity, and interfere the mRNA expression levels of AChRs in A549 cells. The addition of exogenous AChE recombinant protein could reverse the above effects to a certain extent., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

Soybean plants are highly susceptible to Fusarium species, which significantly reduce soybean production and quality. Several Fusarium species have been reported to synthesize mycotoxins, such as trichothecene, which have been related to major human diseases. In November 2021, soybean pods in Nantong municipality, China, showed black necrotic lesions during the harvest stage. The disease incidence reached 69%. The pathogen was identified as Fusarium sulawense via morphological analysis and sequencing of ITS , EF1-α and RPB2 genes. A PCR assay with primers targeting the trichothecene biosynthesis genes suggested that the three isolates could synthesize trichothecenes. The effectiveness of fungicide carbendazim and natural metabolites dipicolinic acid and kojic acid was screened for the management of F. sulawense on postharvest soybean pods. The highest efficacy was obtained when combining 3.8 mg/mL carbendazim and 0.84 mg/mL dipicolinic acid (curative efficacy: 49.1% lesion length inhibition; preventive efficacy: 82.7% lesion length inhibition), or 1.9 mg/mL carbendazim and 0.71 mg/mL kojic acid (preventive efficacy: 84.9% lesion length inhibition). Collectively, this report will lead to a better understanding of the safety hazards found in soybean products in China and reveals the application of dipicolinic and kojic acids to reduce the use of carbendazim.

Fungal pathogens can invade not only the fruit peel but also the outer part of the fruit mesocarp, limiting the efficacy of fungicides. In this study, the relationships between fungicide structure, diffusion capacity and in vivo efficacy were evaluated for the first time. The diffusion capacity from pear peel to mesocarp of 11 antifungal compounds, including p -aminobenzoic acid, carbendazim, difenoconazole, dipicolinic acid, flusilazole, gentamicin, kojic acid, prochloraz, quinolinic acid, thiophanate methyl and thiram was screened. The obtained results indicated that size and especially polarity were negatively correlated with the diffusion capacity. Although some antifungal compounds, such as prochloraz and carbendazim, were completely degraded after a few days in peel and mesocarp, other compounds, such as p -aminobenzoic acid and kojic acid, showed high stability. When applying the antifungal compounds at the EC 50 concentrations, it was observed that the compounds with high diffusion capacity showed higher in vivo antifungal activity against Alternaria alternata than compounds with low diffusion capacity. In contrast, there was no relationship between stability and in vivo efficacy. Collectively, the obtained results indicated that the diffusion capacity plays an important role in the efficacy of fungicides for the control of pear fruit diseases.

Skeletal muscle regeneration is essential for maintaining muscle function in injury and muscular disease. Myogenesis plays key roles in forming new myofibers during the process. Here, through bioinformatic screen for the potential regulators of myogenesis from 5 independent microarray datasets, we identify an overlapping differentially expressed gene (DEG) optineurin (OPTN). Optn knockdown (KD) delays muscle regeneration in mice and impairs C2C12 myoblast differentiation without affecting their proliferation. Conversely, Optn overexpression (OE) promotes myoblast differentiation. Mechanistically, OPTN increases nuclear levels of β-catenin and enhances the T-cell factor/lymphoid enhancer factor (TCF/LEF) transcription activity, suggesting activation of Wnt signaling pathway. The activation is accompanied by decreased protein levels of glycogen synthase kinase 3β (GSK3β), a negative regulator of the pathway. We further show that OPTN physically interacts with and targets GSK3β for autophagic degradation. Pharmacological inhibition of GSK3β rescues the impaired myogenesis induced by Optn KD during muscle regeneration and myoblast differentiation, corroborating that GSK3β is the downstream effector of OPTN-mediated myogenesis. Together, our study delineates the novel role of OPTN as a potential regulator of myogenesis and may open innovative therapeutic perspectives for muscle regeneration., Competing Interests: The authors have declared that no competing interests exist.

Sclerotinia stem rot, which is caused by the fungal pathogen Sclerotinia sclerotiorum , is a soybean disease that results in enormous economic losses worldwide. The control of S. sclerotiorum is a difficult task due to the pathogen's wide host range and its persistent structures, called sclerotia. In addition, there is lack of soybean cultivars with medium to high levels of resistance to S. sclerotiorum . In this work, kojic acid (KA), a natural bioactive compound commonly used in cosmetic industry, was evaluated for the management of Sclerotinia stem rot. Interestingly, KA showed strong antifungal activity against S. sclerotiorum by inhibiting chitin and melanin syntheses and, subsequently, sclerotia formation. The antifungal activity of KA was not obviously affected by pH, but was reduced in the presence of metal ions. Treatment with KA reduced the content of virulence factor oxalic acid in S. sclerotiorum secretions. Preventive applications of 50 mM KA (7.1 mg/ml) completely inhibited S. sclerotiorum symptoms in soybean; whereas, in curative applications, the combination of KA with prochloraz and carbendazim improved the efficacy of these commercial fungicides. Taken together, the antifungal activity of KA against S. sclerotiorum was studied for the first time, revealing new insights on the potential application of KA for the control of Sclerotinia stem rot in soybean., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhu, Shi, Wang, Wang and Laborda.)

Elevated circulating levels of growth differentiation factor 15 (GDF15) have been shown to reduce food intake and lower body weight through activation of hindbrain receptor glial-derived neurotrophic factor (GDNF) receptor alpha-like (GFRAL) in rodents and nonhuman primates, thus endogenous induction of this peptide holds promise for obesity treatment. Here, through in silico drug-screening methods, we found that small molecule Camptothecin (CPT), a previously identified drug with potential antitumor activity, is a GDF15 inducer. Oral CPT administration increases circulating GDF15 levels in diet-induced obese (DIO) mice and genetic ob/ob mice, with elevated Gdf15 expression predominantly in the liver through activation of integrated stress response. In line with GDF15's anorectic effect, CPT suppresses food intake, thereby reducing body weight, blood glucose, and hepatic fat content in obese mice. Conversely, CPT loses these beneficial effects when Gdf15 is inhibited by a neutralizing antibody or AAV8-mediated liver-specific knockdown. Similarly, CPT failed to reduce food intake and body weight in GDF15's specific receptor GFRAL-deficient mice despite high levels of GDF15. Together, these results indicate that CPT is a promising anti-obesity agent through activation of GDF15-GFRAL pathway., Competing Interests: The authors have declared that no competing interests exist.

Background: Constructing an ideal model of abdominal aortic aneurysm (AAA) is of great significance to elucidate its complex pathogenesis. Therefore, we introduce a new and simple method to simulate human AAA and construct a rat AAA model through a retroperitoneal approach., Methods: Forty healthy adult Sprague Dawley (SD) rats were randomly divided into a control group, elastase + calcium chloride group (PPE+CaCl 2 ), elastase group (PPE), and elastase + beta aminopropionitrile group (PPE+BAPN) according to a male-female ratio of 1:1, with 10 rats in each group. A retroperitoneal approach was used to free the infrarenal abdominal aorta in all four groups. In the PPE + CaCl 2 group, 0.1 ml of elastase (approximately 5 U) was perfused into the arterial cavity for 20 min, and 1.0 mol/L calcium chloride was infiltrated out of the arterial cavity for 10 min. In the PPE group, 0.1 mL of elastase (approximately 5U) was perfused into the arterial cavity for 20 min, and normal saline was infiltrated out of arterial cavity for 10 min; the PPE + BAPN group combined with 0.3% BAPN drinking water/day on the basis of PPE group; the control group was treated with saline instead of elastase and calcium chloride. Abdominal aortic specimens were collected after 4 weeks of feeding. The diagnostic criteria of AAA were 50% dilation of the abdominal aorta or rupture of the aneurysm at 4 weeks after the operation. Histopathology, immunohistochemistry, quantitative PCR (qPCR), western blotting assay, gelatine zymogram, and other methods were used., Results: The operation time of the four groups was controlled at approximately 40 min, and the success rate of the operation was 100%. Survival rate: Control Group (100%) = PPE Group (100%) > PPE + CaCl 2 Group (90%) > PPE + BAPN Group (40%); Aneurysm formation rate: PPE + BAPN Group (100%) > PPE + CaCl 2 Group (80%) > PPE Group (60%) > Control Group (0%); Aneurysm rupture rate: PPE + BAPN group (60%) > PPE + CaCl 2 group (12.5%) > PPE group (0%);Inflammatory cells (macrophages, T cells, B cells, dendritic cells) infiltrated in different degrees in the PPE + CaCl 2 , PPE and PPE + BAPN groups. Vascular thickness, elastic fiber content, collagen fiber content, and vascular smooth muscle cell content in the PPE + CaCl 2 group and PPE + BNPA group were significantly lower than those in Control group ( P < 0.05). The content of elastic fibers and vascular smooth muscle cells in the PPE group were significantly lower than that in Control group ( P < 0.05). The expression and activity of matrix metalloproteinase 2 (MMP2) and MMP9 in the PPE + CaCl 2 group, PPE group, and PPE + BNPA group were significantly higher than those in the control group ( P < 0.05)., Conclusions: A new, simple, and reproducible rat AAA model can be constructed by a retroperitoneal approach. The pathological features of the three models are effective simulation of human AAA inflammatory cell infiltration, protease activity enhancement, and extracellular matrix destruction. The PPE+ CaCl 2 model has the advantages of a high survival rate, high aneurysm formation rate, good stability, and reproducibility. It is an ideal animal model for studying the pathogenesis of AAA. The PPE + BAPN model can simulate the characteristics of spontaneous rupture of aneurysms. It is an ideal animal model to study the mechanism of AAA rupture., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhu, Tang, Zhou, Shi, Yi and Yang.)

Background: Berry syndrome is a challenging disease for surgeons to make early diagnosis and successful surgical correction in the neonatal period. Here, we summarized the clinical features of three neonates with berry syndrome in our center to optimize the therapeutic effect in the future., Methods: From January 2014 to December 2019, three neonates with berry syndrome underwent one-stage surgical repair in our center. We mainly used two different surgical techniques to repair it, and collected clinical data retrospectively from hospitalization history, outpatient records, and telephone follow-up., Results: The age at operation was 28, 8, and 8 days and the body weight was 3.65, 3.86, and 3.0 kg, respectively. The morphology of the interrupted aortic arch (IAA) was type A in two patients and type B in one patient. The aortopulmonary window (APW) morphology was type IIa, III, and IIb, respectively. The phenotype of the IAA type B combined with APW type III in our second patient was reported for the first time so far. All patients survived and were followed up to date. The second patient using intra-aortic baffle experienced twice reoperation for right pulmonary artery (RPA) stenosis. All patients grew well so far., Conclusion: Once diagnosed in the neonatal period, berry syndrome can be safely corrected by one-stage surgical repair in experienced cardiac centers. Considering the variability of the location where the RPA arises from the posterior wall of the aorta, it is difficult to find the best surgical method for each patient., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shi, Weng, Yu, Ma, Pu, Ying and Yu.)

Moyamoya disease (MMD) is a rare cause of chorea, and its pathophysiological mechanism remains unclear. We explore the use of cerebral positron emission tomography (PET) to study brain functional connectivity in 2 patients with MMD-induced hemichorea. Abnormal metabolism of brain was analyzed by 18 F-fluorodeoxyglucose ( 18 F-FDG) PET images. Dopamine transporters (DAT) PET evaluated the integrity of the cerebral dopamine system. A comprehensive systemic literature search of the PubMed database was also conducted. The 18 F-FDG imaging of our patients showed no responsible hypometabolism in affected brain areas, while hypermetabolism in the affected caudate nucleus, putamen and fronto-parietal areas could be seen. DAT PET imaging was normal in patient 1 (a 23-year-old woman), while remarkably reduced DAT binding was seen in the left striatum of patient 2 (a 48-year-old woman). The literature review of 9 publications revealed that 11 patients who underwent single photon emission computed tomography (SPECT) showed cerebral hypoperfusion in the cortex and subcortical area; 18 F-FDG PET was performed in 3 cases, which revealed hypermetabolism in the affected striatum in 2 cases. These findings suggest that the striatal and cortical hypermetabolism in the first patient result from underactivity in indirect pathway from basal ganglia-thalamocortical circuits, causing increased activity of excitatory glutamatergic thalamostriatal and thalamocortical projection neurons. The collateral vessels in the basal ganglia might lead to disruption of normal basal ganglia signaling. A dominant left hemisphere with corpus callosal connections to the right basal ganglia resulting into left hemichorea is the most probable explanation for the second patient. We have identified abnormal functional connectivity in basal ganglia-thalamocortical circuits in patients with MMD-induced chorea highlighting the corticostriatal pathway plays an important role in the pathogenesis of MMD-induced chorea., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Xian, Zhang, Shi, Luo, Yi and Pei.)

It is difficult to differentiate between Parkinson's disease and multiple system atrophy parkinsonian subtype (MSA-P) because of the overlap of their signs and symptoms. Enormous efforts have been made to develop positron emission tomography (PET) imaging to differentiate these diseases. This study aimed to investigate the co-registration analysis of 18 F-fluorodopa and 18 F-flurodeoxyglucose PET images to visualize the difference between Parkinson's disease and MSA-P. We enrolled 29 Parkinson's disease patients, 28 MSA-P patients, and 10 healthy controls, who underwent both 18 F-fluorodopa and 18 F-flurodeoxyglucose PET scans. Patients with Parkinson's disease and MSA-P exhibited reduced bilateral striatal 18 F-fluorodopa uptake ( p < 0.05, vs. healthy controls). Both regional specific uptake ratio analysis and statistical parametric mapping analysis of 18 F-flurodeoxyglucose PET revealed hypometabolism in the bilateral putamen of MSA-P patients and hypermetabolism in the bilateral putamen of Parkinson's disease patients. There was a significant positive correlation between 18 F-flurodeoxyglucose uptake and 18 F-fluorodopa uptake in the contralateral posterior putamen of MSA-P patients ( r s = 0.558, p = 0.002). Both 18 F-flurodeoxyglucose and 18 F-fluorodopa PET images showed that the striatum was rabbit-shaped in the healthy control group segmentation analysis. A defective rabbit-shaped striatum was observed in the 18 F-fluorodopa PET image of patients with Parkinson's disease and MSA-P. In the segmentation analysis of 18 F-flurodeoxyglucose PET image, an intact rabbit-shaped striatum was observed in Parkinson's disease patients, whereas a defective rabbit-shaped striatum was observed in MSA-P patients. These findings suggest that there were significant differences in the co-registration analysis of 18 F-flurodeoxyglucose and 18 F-fluorodopa PET images, which could be used in the individual analysis to differentiate Parkinson's disease from MSA-P., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Xian, Shi, Luo, Yi, Zhang and Pei.)

Hexavalent chromium (Cr(VI)) is a carcinogenic compound that can be removed from contaminated sites by the activity of metal-reducing bacteria. The model bacterium Geobacter sulfurreducens reduces Cr(VI) to less toxic Cr(III) and accumulates Cr ions intracellularly. However, this process is usually slow with small concentrations of Cr(VI) removed in a matter of days. Here, high-density G. sulfurreducens cultures were tested for the capacity to remove Cr(VI) readily. With an initial G. sulfurreducens density of 5.8 × 10 8  cells ml -1 , 99.0 ± 0.8% of 100 mg l -1 Cr(VI) was removed after 20 min. With a higher starting Cr(VI) concentration of 200 mg l -1 , G. sulfurreducens with a density of 11.4 × 10 8  cells ml -1 removed 99.0 ± 0.4% Cr(VI) after 2 h. Experiments performed with cell-free spent medium indicate that extracellular proteins are major contributors for the reduction of Cr(VI) to Cr(III). Furthermore, results show that most Cr(III) ions ultimately end up inside the bacterial cells where they are less susceptible to re-oxidation. The fast Cr(VI) removal rates observed with high-density G. sulfurreducens demonstrate the potential of this bacterium for bioremediation applications such as the cleaning of industrial wastewaters., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The signaling pathways induced by Pseudomonas putida in rice plants at the early plant-rhizobacteria interaction stages, with and without inoculation of Xanthomonas oryzae pv. oryzae , were studied. In the absence of pathogen, P. putida reduced ethylene (ET) production, and promoted root and stem elongation. Interestingly, gene OsHDA702 , which plays an important role in root formation, was found significantly up-regulated in the presence of the rhizobacterium. Although X. oryzae pv. oryzae inoculation enhanced ET production in rice plants, P. putida treatment repressed ET-, jasmonic acid (JA)- and salicylic acid (SA)-mediated defense pathways, and induced the biosynthesis of abscisic acid (ABA), and the overexpression of OsHDA705 and some pathogenesis-related proteins (PRs), which in turn increased the susceptibility of the rice plants against the pathogen. Collectively, this is the first work on the defense signaling induced by plant growth-promoting rhizobacteria in plants at the early interaction stages, and suggests that rhizobacteria stimulate an alternative defense mechanism in plants based on ABA accumulation and OsHDA705 signaling.

Multiple Fe(III)-reducing Geobacter species including the model Geobacter sulfurreducens are thought to be incapable of carbon dioxide fixation. The discovery of the reversed oxidative tricarboxylic acid cycle (roTCA) for CO 2 reduction with citrate synthase as key enzyme raises the possibility that G. sulfurreducens harbors the metabolic potential for chemolithoautotrophic growth. We investigate this hypothesis by transferring G. sulfurreducens PCA serially with Fe(III) as electron acceptor and formate as electron donor and carbon source. The evolved strain T17-3 grew chemolithoautotrophically with a 2.7-fold population increase over 48 h and a Fe(III) reduction rate of 417.5 μM h -1 . T17-3 also grew with CO 2 as carbon source. Mutations in T17-3 and enzymatic assays point to an adaptation process where the succinyl-CoA synthetase, which is inactive in the wild-type, became active to complete the roTCA cycle. Deletion of the genes coding for the succinyl-CoA synthetase in T17-3 prevented growth with formate as substrate. Enzymatic assays also showed that the citrate synthase can perform the necessary cleavage of citrate for the functional roTCA cycle. These results demonstrate that G. sulfurreducens after adaptation reduced CO 2 via the roTCA cycle. This previously hidden metabolism can be harnessed for biotechnological applications and suggests hidden ecological functions for Geobacter.

Valsa pyri is a fatal canker pathogen that causes significant reduction of crop yield in pear orchards. V. pyri invades the trunk phloem, and is difficult to control by chemical treatment. In this work, it was found for the first time that Bacillus subtilis -produced dipicolinic acid (DPA) exhibits antifungal activity against different canker pathogens, including Alteraria alternata , Botryosphaeria dothidea , Rhizoctonia solani , and V. pyri . Growth inhibition of V. pyri was observed at less than 5 mM concentration (pH = 5.6). DPA showed the highest antifungal activity at acidic pH values and in the presence of bivalent metals, such as zinc(II), cobalt(II), and copper(II). Measurement of mRNA expression levels and scanning electron microscope (SEM) observations revealed that DPA causes V. pyri apoptosis via inhibition of chitin biosynthesis and subsequent cell lysis. Interestingly, DPA showed high stability in the pear bark and was able to cross the pear tree bark into the phloem, protecting the internal phases of the pear trunk. In preventive applications, DPA reduced the canker symptoms of V. pyri on Cuigan pear trees by 90%. Taken together, an efficient strategy for the management of V. pyri -caused canker disease was developed using a novel antifungal agent, DPA, with strong antifungal activity and particular diffusion properties., (Copyright © 2020 Song, Han, He, Wang, Li, Wu, Huang, Liu, Liu, Laborda and Shi.)

Objectives: To explore the characteristics of IDH and TERT promoter mutations in gliomas in Chinese patients., Methods: A total of 124 Chinese patients with gliomas were enrolled to study the frequencies of mutations in isocitrate dehydrogenase (IDH) and telomerase reverse transcriptase promoter (TERTp). Among the 124 patients, 59 patients were enrolled to study the classification of gliomas based on mutations in IDH and TERTp., Results: Isocitrate dehydrogenase mutations are positively correlated with a good prognosis but mutations in TERTp cannot predict prognoses independently. The combined analysis of the mutations of IDH and TERTp can predict the prognosis more accurately. Patients with IDH and TERTp glioma mutations have the best prognosis, followed by only IDH mutation patients and only TERTp mutation patients, which have the worst prognosis. IDH and TERTp mutations occur frequently in males, younger patients or lower-grade patients. In contrast, only TERTp mutations occur frequently in females, older patients or higher-grade patients., Conclusions: Patients with IDH and TERTp glioma mutations have the best prognosis, and only IDH mutation patients and only TERTp mutation patients have the worst prognosis. Moreover, the molecular classification of gliomas by mutations of IDH and TERTp is not suitable for pediatric patients., (© 2020 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.)

Obesity leads to multiple health problems, including diabetes, fatty liver, and even cancer. Here, we report that urolithin A (UA), a gut-microflora-derived metabolite of pomegranate ellagitannins (ETs), prevents diet-induced obesity and metabolic dysfunctions in mice without causing adverse effects. UA treatment increases energy expenditure (EE) by enhancing thermogenesis in brown adipose tissue (BAT) and inducing browning of white adipose tissue (WAT). Mechanistically, UA-mediated increased thermogenesis is caused by an elevation of triiodothyronine (T3) levels in BAT and inguinal fat depots. This is also confirmed in UA-treated white and brown adipocytes. Consistent with this mechanism, UA loses its beneficial effects on activation of BAT, browning of white fat, body weight control, and glucose homeostasis when thyroid hormone (TH) production is blocked by its inhibitor, propylthiouracil (PTU). Conversely, administration of exogenous tetraiodothyronine (T4) to PTU-treated mice restores UA-induced activation of BAT and browning of white fat and its preventive role on high-fat diet (HFD)-induced weight gain. Together, these results suggest that UA is a potent antiobesity agent with potential for human clinical applications., Competing Interests: The authors have declared that no competing interests exist.

The prevalence of obesity has increased dramatically worldwide in the past ~50 years. Searching for safe and effective anti-obesity strategies are urgently needed. Lactucin, a plant-derived natural small molecule, is known for anti-malaria and anti-hyperalgesia. The study is to investigate whether lactucin plays a key role in adipogenesis. To this end, in vivo male C57BL/6 mice fed a high-fat diet (HFD) were treated with 20 mg/kg/day of lactucin or vehicle by gavage for seven weeks. Compared with vehicle-treated controls, Lactucin-treated mice showed lower body mass and mass of adipose tissue. Consistently, in vitro 3T3-L1 cells were treated with 20 μM of lactucin. Compared to controls, lactucin-treated cells showed significantly less lipid accumulation during adipocyte differentiation and lower levels of lipid synthesis markers. Mechanistically, we showed the anti-adipogenic property of lactucin was largely limited to the early stage of adipogenesis. Lactucin-treated cells fail to undergo mitotic clonal expansion (MCE). Further studies demonstrate that lactucin-induced MCE arrests might result from reduced phosphorylation of JAK2 and STAT3. We then asked whether activation of JAK2/STAT3 would restore the inhibitory effect of lactucin on adipogenesis with pharmacological STAT3 activator colivelin. Our results revealed similar levels of lipid accumulation between lactucin-treated cells and controls in the presence of colivelin, indicating that inactivation of STAT3 is the limiting factor for the anti-adipogenesis of lactucin in these cells. Together, our results provide the indication that lactucin exerts an anti-adipogenesis effect, which may open new therapeutic options for obesity.

Four new diterpenoids, named aspidoptoids A-D ( 1 - 4 ), together with two known analogues ( 5 - 6 ) were isolated from Aspidopterys obcordata vine. Aspidoptoids A-B ( 1 - 2 ) are the first examples of phenylethylene-bearing 20-nor-diterpenoids of which aspidoptoid B ( 2 ) possesses a rare 3,10-oxybridge. Their structures and absolute configuration were determined by extensive spectroscopic analyses (IR, HRESIMS, 1D and 2D NMR) and electronic circular dichroism (ECD) calculation. In addition, all the isolates were evaluated for their cytotoxic activities and inhibitory effects on the nitric oxide (NO) production., Competing Interests: The authors declare no conflict of interest.

90% of the world population is exposed to heavy atmospheric pollution. This is a major public health issue causing 7 million death each year. Air pollution comprises an array of pollutants such as particulate matters, ozone and carbon monoxide imposing a multifactorial stress on living cells. Here, Escherichia coli was used as model cell and adapted for 390 generations to atmospheric pollution to assess its long-term effects at the genetic, transcriptomic and physiological levels. Over this period, E. coli evolved to grow faster and acquired an adaptive mutation in rpoB, which encodes the RNA polymerase β subunit. Transcriptomic and biochemical characterization showed alteration of the cell membrane composition resulting in lesser permeability after the adaptation process. A second significant change in the cell wall structure of the adapted strain was the greater accumulation of the exopolysaccharides colanic acid and cellulose in the extracellular fraction. Results also indicated that amino acids homeostasis was involved in E. coli response to atmospheric pollutants. This study demonstrates that adaptive mutation with transformative physiological impact can be fixed in genome after exposure to atmospheric pollution and also provides a comprehensive portrait of the cellular response mechanisms involved.

To investigate the protein-sparing effect of α-lipoic acid (LA), experimental fish (initial body weight: 18·99 (sd 1·82) g) were fed on a 0, 600 or 1200 mg/kg α-LA diet for 56 d, and hepatocytes were treated with 20 μm compound C, the inhibitor of AMP kinase α (AMPKα), treated for 30 min before α-LA treatment for 24 h. LA significantly decreased lipid content of the whole body and other tissues (P0·05). Consistent with results from the experiment in vitro, LA activated phosphorylation of AMPKα and notably increased the protein content of adipose TAG lipase in intraperitoneal fat, hepatopancreas and muscle in vivo (P<0·05). Meanwhile, LA significantly up-regulated the mRNA expression of genes involved in fatty acid β-oxidation in the same three areas, and LA also obviously down-regulated the mRNA expression of genes involved in amino acid catabolism in muscle (P<0·05). Besides, it was observed that LA significantly activated the mammalian target of rapamycin (mTOR) pathway in muscle of experimental fish (P<0·05). LA could promote lipolysis and fatty acid β-oxidation via increasing energy supply from lipid catabolism, and then, it could economise on the protein from energy production to increase protein deposition in grass carp. Besides, LA might directly promote protein synthesis through activating the mTOR pathway.

G0/G1 switch gene 2 plays an important role in the regulation of lipolysis in mammals, but little is known about its gene (G0S2) structure and function in fish. In the present study, two genes, G0S2a and G0S2b were isolated and characterized from grass carp Ctenopharyngodon idella, which encode peptides of 111 and 84 amino acids, respectively. Moreover, alternative multiple exon usage resulted in a significant variation in the 5'-region of G0S2a transcripts yielding two isoforms (G0S2a1 and G0S2a2). Phylogenetic and synteny analyses indicated that G0S2a and G0S2b could have originated from the teleost-specific genome duplication event. Analysis of the exon-intron structures clarified that G0S2a contained an extra intron compared with G0S2b. G0S2a1, G0S2a2 and G0S2b mRNAs were highly expressed in adipose tissue and liver. G0S2a was localized to the cytoplasm and nucleus, while G0S2b was mainly localized in cytoplasm, suggesting that G0S2a and G0S2b may have different functions in grass carp. PPARα agonist caused an increase in G0S2a1 and G0S2b expression, revealing that they are subject to transcriptional control by PPARα-mediated signals. TNF-α treatment decreased G0S2a1 and G0S2a2 transcripts that paralleled TNF-α downregulation of PPARα; however, only the effects of TNF-α on G0S2a1 were attenuated by treatment with PPARα agonist. Our findings identify G0S2a, not G0S2b, as a target gene for TNF-α and reveal that TNF-α suppresses G0S2a1 gene expression through a PPARα-dependent pathway in grass carp hepatocytes., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Gallbladder adenomyomatosis (GAM) is an acquired, reactive, tumor-like condition. Malignant transformation is extremely rare, and imaging features during contrast-enhanced ultrasound (CEUS) have not been described before. Herein, we describe a 73-year-old Asian man who had been diagnosed with gallbladder carcinoma by conventional ultrasonography (US). Based on additional radiological findings, we believed that it was a localized adenomyomatosis. However, the histopathological diagnosis was adenocarcinoma originate from adenomyomatosis with serosal invasion. We believe this is the first case of adenocarcinoma derived from GAM with characteristics of CEUS findings. This case is presented to indicate a clinical awareness of malignant transformation of GAM and discuss the radiology significance with an emphasis on CEUS., Competing Interests: There are no conflicts of interest

Pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNFα), may contribute to hepatic steatosis in the situation of excess lipid accumulation in farmed fish. Pigment epithelium-derived factor (PEDF) is an endogenous anti-inflammatory factor and promotes lipolysis. Accordingly, we isolated PEDF from grass carp and investigated its role in TNFα-induced hepatic steatosis. Sequence analysis showed that PEDF gene, which possesses 8 exons and 7 introns, encodes a protein with 409 amino acids. PEDF was a critical determinant of the transcriptional response to nutrient availability in grass carp. Endogenous PEDF was an intracellular protein with cytoplasmic distribution and directly interacts with adipose triglyceride lipase (ATGL), which might mediate PEDF-induced lipolysis. TNFα significantly promoted lipid accumulation in vivo and in vitro, accompanied with a decrease in mRNA levels of PEDF and peroxisome proliferator-activated receptor alpha (PPARα). Recombinant PEDF and PPARα agonist diminished the TNFα-induced hepatic steatosis. Meanwhile, PPARα agonist caused an increase in PEDF expression, suggesting that TNFα antagonizes the actions of PEDF possibly in a PPARα-dependent manner. These findings suggest that PEDF is an important protective factor against hepatic steatosis induced by TNFα, which provided a new therapeutic target for inflammation-associated hepatic steatosis., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Functional magnetic resonance imaging (fMRI) is a promising method for quantifying brain recovery and investigating the intervention-induced changes in corticomotor excitability after stroke. This study aimed to evaluate cortical reorganization subsequent to virtual reality-enhanced treadmill (VRET) training in subacute stroke survivors., Methods: Eight participants with ischemic stroke underwent VRET for 5 sections per week and for 3 weeks. fMRI was conducted to quantify the activity of selected brain regions when the subject performed ankle dorsiflexion. Gait speed and clinical scales were also measured before and after intervention., Results: Increased activation in the primary sensorimotor cortex of the lesioned hemisphere and supplementary motor areas of both sides for the paretic foot ( p < 0.01) was observed postintervention. Statistically significant improvements were observed in gait velocity ( p < 0.05). The change in voxel counts in the primary sensorimotor cortex of the lesioned hemisphere is significantly correlated with improvement of 10 m walk time after VRET ( r = -0.719)., Conclusions: We observed improved walking and increased activation in cortical regions of stroke survivors after VRET training. Moreover, the cortical recruitment was associated with better walking function. Our study suggests that cortical networks could be a site of plasticity, and their recruitment may be one mechanism of training-induced recovery of gait function in stroke. This trial is registered with ChiCTR-IOC-15006064.

Background: Nontuberculous Mycobacterium (NTM) bloodstream infection (BSI) is relatively rare. We aimed in this study to evaluate the clinical characteristics, laboratory evaluation, and outcomes of patients with NTM BSI., Methods: We retrospectively reviewed the clinical records of inpatients with NTM BSI at our institution between January 2008 and January 2015 and recorded clinical parameters including age, gender, underlying disease, clinical manifestation, organs involved with NTM disease, species of NTM, laboratory data, treatment and outcome of these patients. We also reviewed the reported cases and case series of NTM BSI by searching PubMed, EMBASE, and Wanfang databases. Data of normal distribution were expressed by mean ± standard deviation (SD). Data of nonnormal distribution were expressed by median and interquartile range (IQR)., Results: Among the ten patients with NTM BSI, the median age was 51 years (IQR 29-57 years) and three patients were males. Eight patients were immunocompromised, with underlying diseases including human immunodeficiency virus (HIV) infection (one patient), rheumatic diseases (two patients), breast cancer (one patient), myelodysplastic syndrome (two patients), and aplastic anemia (two patients). Other organ(s) involved were lung (two patients), endocardium (two patients), brain, spinal cord, and soft tissue (one each patient). The median lymphocyte was 0.66 × 109/L (IQR 0.24-1.93 × 109/L). The median cluster of differentiation 4 (CD4) cell count was 179/mm3 (IQR 82-619/mm3). Five patients died (three with hematological diseases, one with breast cancer, and one with rheumatic disease), three recovered, and two were lost to follow-up., Conclusions: We reported all cases in our hospital diagnosed with bloodstream NTM infection that was rarely reported. In this group of patients, patients usually had a high fever and could have multiple organ involvements. All patients with poor prognosis had underlying diseases.

Background: Tuberculosis (TB) remains a worldwide problem. Intestinal TB (ITB) constitutes a major public health problem in developing countries and has been associated with significant morbidity and mortality. The aim of this study was to characterize the clinical, radiological, endoscopic, and pathological features of ITB and to define the strategy for establishing the diagnosis., Methods: A retrospective study (from January 2000 to June 2015) was carried out in Peking Union Medical College Hospital and all hospitalized cases were diagnosed as ITB during the study period were included. The relevant clinical information, laboratory results, microbiological, and radiological investigations were recorded., Results: Of the 85 cases, 61 cases (71.8%) were ranged from 20 to 50 years. The ileocecal region was involved in about 83.5% (71/85) of patients. About 41.2% (35/85) of patients had co-existing extra ITB, especially active pulmonary TB. Abdominal pain (82.4%) was the most common presenting symptom followed by weight loss (72.9%) and fever (64.7%). Both T-cell spot of TB test (T-SPOT.TB) and purified protein derivatives (PPD) tests were performed in 26 patients: 20 (76.9%) positive T-SPOT.TB and 13 (50.0%) positive PPD were detected, with a statistical significant difference (P = 0.046). Twenty cases (23.5%) were histopathology and/or pathogen confirmed TB; 27 cases (31.8%) were diagnosed by clinical manifestation consistent with ITB and evidence of active extra ITB; 38 cases (44.7%) were diagnosed by good response to diagnostic anti-TB therapy., Conclusions: ITB is difficult to diagnose even with modern medical techniques due to its nonspecific clinical and laboratory features. At present, combination of clinical, endoscopic, radiological, and pathological features continues to be the key to the diagnosis of ITB.

Background: Tuberculosis (TB) remains a major global public health challenge. Articular TB is an important form of extrapulmonary tuberculosis, and its diagnosis is difficult because of the low sensitivity of traditional methods. The aim of this study was to analyze the diagnostic value of T-SPOT.TB on synovial fluid for the diagnosis of articular TB., Methods: Patients with suspected articular TB were enrolled consecutively between August 2011 and December 2015. T-SPOT.TB was performed on both synovial fluid mononuclear cells (SFMCs) and peripheral blood mononuclear cells (PBMCs). The final diagnosis of articular TB was independent of the T-SPOT.TB result. The diagnostic sensitivity, specificity, predictive value, and likelihood ratio of T-SPOT.TB on SFMCs and PBMCs were analyzed., Results: Twenty patients with suspected articular TB were enrolled. Six were diagnosed with articular TB, and 14 patients were diagnosed with other diseases. Sensitivity and specificity were 83% and 86% for T-SPOT.TB on SFMCs, and 67% and 69% for T-SPOT.TB on PBMCs, respectively. The positive predictive value (PPV) and negative predictive value (NPV) of T-SPOT.TB on SFMCs were 71% and 92%, respectively. The PPV and NPV were 50% and 82% for T-SPOT.TB on PBMCs., Conclusion: Sensitivity, specificity, and NPV of T-SPOT.TB on SFMCs appeared higher than that on PBMCs, indicating that T-SPOT.TB on SFMCs might be a rapid and accurate diagnostic test for articular TB.

Background: Water-forming NADH oxidase can oxidize cytosolic NADH to NAD(+), thus relieving cytosolic NADH accumulation in Saccharomyces cerevisiae. Previous studies of the enzyme were conducted under aerobic conditions, as O2 is the recognized electron acceptor of the enzyme. In order to extend its use in industrial production and to study its effect on anaerobes, the effects of overexpression of this oxidase in S. cerevisiae BY4741 and Clostridium acetobutylicum 428 (Cac-428) under anaerobic conditions were evaluated., Results: Glucose was exhausted in the NADH oxidase-overexpressing S. cerevisiae strain (Sce-NOX) culture after 26 h, while 43.51 ± 2.18 g/L residual glucose was left in the control strain (Sce-CON) culture at this time point. After 30 h of fermentation, the concentration of ethanol produced by Sce-NOX reached 36.28 ± 1.81 g/L, an increase of 56.38 % as compared to Sce-CON (23.20 ± 1.16 g/L), while the byproduct glycerol was remarkably decreased in the culture of Sce-NOX. In the case of the C. acetobutylicum strain (Cac-NOX) overexpressing NADH oxidase, glucose consumption, cell growth rate, and the production of acetone-butanol-ethanol (ABE) all decreased, while the concentrations of acetic acid and butyric acid increased as compared to the control strain (Cac-CON). During fermentation of Cac-CON and Cac-NOX in 100-mL screw-capped bottles, the concentrations of ABE increased with increasing headspace. Additionally, several alternative electron acceptors in C. acetobutylicum fermentation were tested. Nitroblue tetrazolium and 2,6-dichloroindophenol were lethiferous to both Cac-CON and Cac-NOX. Methylene blue could relieve the effect caused by the overexpression of the NADH oxidase on the metabolic network of C. acetobutylicum strains, while cytochrome c aggravated the effect., Conclusions: The water-forming NADH oxidase could regulate the metabolism of both the S. cerevisiae and the C. acetobutylicum strains in anaerobic conditions. Thus, the recombinant S. cerevisiae strain might be useful in industrial production. Besides the recognized electron acceptor O2, methylene blue and/or the structural analogs may be the alternative elector acceptor of the NADH oxidase in anaerobic conditions.

Background: Cardiac sympathetic nerve sprouting and the dysregulation of β-adrenergic receptor (β-AR) play a critical role in the deterioration of cardiac function after myocardial infarction (MI). Growing evidence indicates that exercise provides protection against MI. The aims of this study were to investigate whether aerobic exercise following MI could inhibit sympathetic nerve sprouting and restore the balance of β3-AR/β1-AR., Methods: Male Sprague-Dawley rats were divided into three groups: sham-operated control group (SC), MI group (MI), and MI with aerobic exercise group (ME). The rats in ME group were assigned to 8 weeks of exercise protocol (16 m/min, 50 min/d, 5 d/wk). The expression of nerve growth factor (NGF), the sympathetic nerve marker-tyrosine hydroxylase (TH), the nerve sprouting marker-growth associated protein 43 (GAP43), and β1- and β2-AR expression in the peri-infarct area of the left ventricle (LV) were measured by Western blot and immunohistochemistry, while β3-AR expression was determined by Western blot and immunofluorescence. Endothelial nitric oxide synthase (NOS2), phospho-NOS2 (p-NOS2), and neuronal nitric oxide synthase (NOS1) were measured by Western blot., Results: MI increased LV end-diastolic pressure (LVEDP), and decreased LV systolic pressure (LVSP). Compared with the MI group, aerobic exercise significantly decreased LVEDP and increased LVSP. The protein expression of TH, GAP43 and NGF was significantly increased after MI, which was normalized by exercise. Compared with the SC group, the ratios of β2-AR/β1-AR and β3-AR/β1-AR were elevated in the MI group, and the protein expression of β3-AR and NOS1 increased after MI. Compared with the MI group, the ratios of β2-AR/β1-AR and β3-AR/β1-AR were normalized in the ME group, while the protein expression of β3-AR and NOS1 significantly increased, and NOS2 was activated by exercise., Conclusions: Aerobic exercise inhibits cardiac sympathetic nerve sprouting, restores β3-AR/β1-AR balance and increases β3-AR expression through the activation of NOS2 and NOS1 after myocardial infarction.

Objective: The aim of this study was to compare the diagnostic value of (18)F-FDG PET/CT with contrast CT for regional lymph node metastasis of colorectal cancer., Methods: Imaging results of 40 patients with colorectal cancer were retrospectively reviewed, and all the patients underwent both abdomen contrast CT and (18)F-FDG PET/CT imaging. Final diagnosis was made by histopathology., Results: 20 colorectal cancer patients were verified with lymph node metastasis while the other 20 patients were absent. Finally, (18)F-FDG PET/CT produced 4 false-positive patients and 3 false-negative patients. (18)F-FDG PET/CT displayed sensitivity 85.0% (17/20), specificity 80.0% (16/20), positive predictive value 81.0% (17/21), negative predictive value 84.2% (16/19) and accuracy 82.5% (33/40) in the diagnosis of lymph node metastasis. Contrast CT produced 5 false-positive patients and 8 false-negative patients. Contrast CT had the sensitivity 60.0% (12/20), specificity 75.0% (15/20) , positive predictive value 70.6% (12/17), negative predictive value 65.2% (15/23) and accuracy 67.5% (27/40). Sensitivity and specificity of PET/CT was better than of contrast CT, but no statistically significant difference between PET/CT and contrast CT (P = 0.478, P = 0.893; P = 0.344. Fisher's exact test and McNemar test)., Conclusion: Sensitivity and specificity of PET/CT was better than of contrast CT, but no statistically significant difference. Clinical works also need to select the appropriate inspection methods based on the patient's situation.

This study was designed to investigate the expression profile of CYGB, its potential neuroprotective function, and underlying molecular mechanisms using a model of neonatal hypoxia-ischemia (HI) brain injury. Cygb mRNA and protein expression were evaluated within the first 36 h after the HI model was induced using RT-PCR and Western blotting. Cygb mRNA expression was increased at 18 h in a time-dependent manner, and its level of protein expression increased progressively in 24 h. To verify the neuroprotective effect of CYGB, a gene transfection technique was employed. Cygb cDNA and shRNA delivery adenovirus systems were established (Cygb-cDNA-ADV and Cygb-shRNA-ADV, respectively) and injected into the brains of 3-day-old rats 4 days before they were induced with HI treatment. Rats from different groups were euthanized 24 h post-HI, and brain samples were harvested. 2,3,5-Triphenyltetrazolium chloride, TUNEL, and Nissl staining indicated that an up-regulation of CYGB resulted in reduced acute brain injury. The superoxide dismutase level was found to be dependent on expression of CYGB. The Morris water maze test in 28-day-old rats demonstrated that CYGB expression was associated with improvement of long term cognitive impairment. Studies also demonstrated that CYGB can up-regulate mRNA and protein levels of VEGF and increase both the density and diameter of the microvessels but inhibits activation of caspase-2 and -3. Thus, this is the first in vivo study focusing on the neuroprotective role of CYGB. The reduction of neonatal HI injury by CYGB may be due in part to antioxidant and antiapoptotic mechanisms and by promoting angiogenesis.

Background: Despite the recent advances in medicine, fever of unknown origin (FUO) remains a diagnostic and therapeutic challenge even to expert physicians. To increase the knowledge of FUO, we conducted a retrospective study to investigate the causes of FUO and the change of major causes of FUO during the past 26 years., Methods: The clinical data were retrospectively analyzed from 997 patients with FUO hospitalized at the Peking Union Medical College Hospital (PUMCH) between January 2004 and October 2010. Furthermore, the results were compared to that reported in previous studies of FUO in PUMCH since 1985., Results: Of the 997 FUO cases, definite diagnosis was eventually achieved in 797 (79.9%) patients. The most common cause of FUO was infectious diseases (479 cases, 48.0%), with tuberculosis accounting for 45.3% (217/479) of the cases of infections. One hundred and sixty-eight (16.9%) patients were diagnosed with connective tissue diseases, with Still's disease and vasculitis accounted for 31.5% (53/168) and 24.4% (41/168) of this category, respectively. Neoplasms and miscellaneous causes were found in 7.9% (79/997) and 7.1% (71/997), respectively. However, no definite diagnosis had been made in the remaining 200 (20.1%) cases until they were discharged from the hospital., Conclusions: During different periods, infectious diseases, especially tuberculosis, were the leading etiology of FUO and the proportion of tuberculosis had no significant difference. While the frequency of neoplasms was descending, the proportion of lymphoma in neoplasm was ascending; the frequency of undiagnosed cases was increasing, but in most FUO cases the causes can be diagnosed eventually after careful analysis of clinical data.

This in vitro study aims to evaluate the crystal and surface microstructure of dental enamel after cold-light bleaching treatment. Twelve sound human premolars were cross-split into four specimens, namely, mesio-buccal (Group LP), disto-buccal (Group P), mesio-lingual (Group NP) and disto-lingual (Group L) specimens. These four groups were treated using the standard cold-light bleaching procedure, a bleaching agent, a peroxide-free bleaching agent and cold-light, respectively. Before and after treatment, all specimens were analyzed by high-resolution, micro-area X-ray diffraction and scanning electron microscopy. Using a spectrometer, tooth color of all specimens was measured before and after treatment. The phase of the enamel crystals was identified as hydroxyapatite and carbonated hydroxyapatite. After treatment, specimens in Groups LP and P showed significantly weaker X-ray diffraction peaks, significant reduction in crystal size and crystallinity, significant increase in L* but decrease in a* and b*, and obvious alterations in the surface morphology. However, specimens in Groups NP and L did not show any significant changes. The cold-light bleaching treatment leads to demineralization in the enamel surface. The acidic peroxide-containing bleaching agent was the major cause of demineralization, whereas cold-light did not exhibit significant increase or decrease effect on this demineralization.

Objective: To evaluate the diagnostic values of (18)F-sodium fluoride ((18)F-NaF) positron emission tomography/computed tomography (PET/CT) imaging in the detection of bone metastases of lung cancer., Methods: A total of 107 lung cancer patients were diagnosed by histopathology and undergone (18)F-NaF PET-CT imaging., Results: Among them, the histopathologically diagnosed tumors included adenocarcinoma (n = 47), squamous cell carcinoma (n = 19), small cell lung cancer (n = 4) and other malignant types (n = 34). Bone metastases occurred in adenocarcinoma (n = 19) and squamous cell carcinoma (n = 4).(18)F-NaF PET/CT imaging had a high sensitivity of 100% in the diagnosis of bone metastases with malignant lung tumors. And its specificity was 98.7%, accuracy 99% and positive predictive value 97.0%., Conclusion: (18)F-NaF PET-CT imaging can detect the bone metastases of lung cancer preoperatively with a high level of sensitivity and accuracy.

Background: Gene chip array can differentiate isolated mycobacterial strains using various mycobacterium specific probes simultaneously. Gene chip array can evaluate drug resistance to isoniazid and rifampin of tuberculosis strains by detecting drug resistance related gene mutation. This technique has great potential for clinical application. We performed a retrospective study to investigate the capability of gene chip array in the rapid differentiation of species and detection of drug resistance in mycobacterium, and to evaluate its clinical efficacy., Methods: We selected 39 patients (54 clinical mycobacterium isolates), used gene chip array to identify the species of these isolates and detect drug resistance to isoniazid and rifampin in Mycobacterium tuberculosis isolates. Meanwhile, these patients' clinical data were analyzed retrospectively., Results: Among these 39 patients whose mycobacterium culture were positive, 32 patients' isolates were identified as Mycobacterium tuberculosis, all of them were clinical infection. Seven patients' isolates were identified as non-tuberculosis mycobacterium. Analyzed with their clinical data, only two patients were considered as clinical infection, both of them were diagnosed as hematogenous disseminated Mycobacterium introcellulare infection. The other five patients' isolates were of no clinical significance; their clinical samples were all respiratory specimens. Clinical manifestations of tuberculosis and non-tuberculous mycobacterial infections were similar. Isoniazid resistance was detected in two tuberculosis patients, while rifampin resistance was detected in one tuberculosis patient; there was another patient whose Mycobacterium tuberculosis isolate was resistant to both isoniazid and rifampin (belongs to multidrug resistance tuberculosis). The fact that this patient did not respond to routine anti-tuberculosis chemotherapy also confirmed this result., Conclusions: Gene chip array may be a simple, rapid, and reliable method for the identification of most mycobacterial species and detection of drug resistance in Mycobacterium tuberculosis. It is useful in diagnosis, treatment, and hospital infection control of mycobacterial infections, and it may have a great potential for clinical application.

Background: There have been few studies conducted on the oral health status of illegal drug users in China, affecting the development of preventive and therapeutic approaches. The aim of the present study was to investigate and analyze the oral health status of former heroin users treated with methadone in Chengdu, the capital of Sichuan Province in southwestern China., Material/methods: The presence of caries (decayed tooth and root), missing teeth, residual roots, dental prosthetic restoration and periodontal health were investigated in 445 former heroin users treated with methadone (317 males and 128 females). Their ages ranged from 20 to 59 years old., Results: Among the study subjects, the prevalence of decayed/filled teeth was 64.72%, and the mean of decayed/filled teeth score was 2.92. The prevalence of decayed/filled roots was 21.80%, and the mean of decayed/filled roots score was 0.62. The prevalence of missing teeth was 31.46%, and the mean missing teeth score was 0.62. The prevalence of residual roots was 42.02%, with a mean score of 1.06. The rates of gingival bleeding, calculus, shallow pockets periodontal pocket, and deep periodontal pocket were 99.55%, 96.63%, 30.34%, and 2.70%, respectively., Conclusions: The oral health status among the studied former heroin users in Chengdu was poorer than the general population. Better dental care for the former heroin users is needed to promote their oral health.

The present study was undertaken to evaluate the potential cardioprotective effects of apricot kernel oil (AO) on the myocardial ischemia-reperfusion (IR) of rat model in vivo. The rats were divided into five groups: sham-operated, IR, low dose AO-treated IR (LD-AO+IR), medium dose AO-treated IR (MD-AO+IR) and high dose AO-treated IR (HD-AO+IR). All rats were provided with food and water ad libitum. The LD-AO+IR, MD-AO+IR and HD-AO+IR groups were given a daily dose of 2, 6 and 10 ml kg(-1)BW(-1) of AO, respectively, for 14 days prior to the IR operation. Tetrazolium chloride staining revealed that infarct size and the ratio of infarct weight to the total heart weight were decreased significantly in the three AO-treated groups compared to the IR group. The serum creatine kinase and aspartate aminotransferase activities also demonstrated similar beneficial effects. Myocardial catalase, superoxide dismutase, glutathione peroxidase, and constitutive nitric oxide synthase activities, as well as NO concentrations, were all increased, whereas malondialdehyde content and inducible nitric oxide synthase were decreased in AO-treated rats. These findings suggest that apricot kernel oil has potent cardioprotective effects, and could be developed as a nutriment for the treatment and prevention of myocardial infarcts., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

A new isolate of canine distemper virus (CDV), named ZJ7, was isolated from lung tissues of a dog suspected with CDV infection using MDCK cells. The ZJ7 isolate induced cytopathogenic effects of syncytia in MDCK cell after six passages. In order to evaluate pathogenesis of ZJ7 strain, three CDV sero-negative dogs were intranasally inoculated with its virus suspension. All infected dogs developed clinical signs of severe bloody diarrhea, conjunctivitis, ocular discharge, nasal discharge and coughing, fever and weight loss at 21 dpi, whereas the mock group infected with DMEM were normal. The results demonstrated that CDV-ZJ7 strain isolated by MDCK cell was virulent, and the nucleotide and amino acid sequences of strain ZJ7 had no change after isolation by MDCK cell when compared with the original virus from the fresh tissues. Molecular and phylogenetic analyses for the nucleocapsid (N), phosphoprotein (P) and receptor binding haemagglutinin (H) gene of the ZJ7 isolate clearly showed it is joins to the Asia 1 group cluster of CDV strains, the predominant genotype in China.

Background: The prevalence of overweight and obesity in Chinese children and adolescents was increasing during the past few decades. The goal of this study was to investigate the effects of after-school exercise with or without diet restriction on total and central obesity, fitness level, and metabolic profile in overweight Chinese adolescents., Methods: A ten-week weight loss trial was performed using a 2 × 2 block design (exercise × diet). Ninety-three overweight adolescents (average age: (13.6 ± 0.7) years; body mass index (BMI): 22.4 - 34.1 kg/m(2)) were randomly assigned to four groups: 1) diet (D); 2) exercise (EX); 3) diet plus exercise (DEX); and 4) overweight control (C). Caloric intake recipes were enacted based on individual age and corresponding ideal body weight. One-hour after-school exercise was performed once per day, four days per week for ten weeks. Changes of anthropometry, body composition, aerobic fitness, and metabolic biomarkers were determined., Results: Groups D, EX and DEX had a significant decrease in BMI (P < 0.01) after the intervention. The percentage of body and truncal fat, and waist circumference were independently reduced by exercise (P < 0.05 and P < 0.01), but not diet. The decrease in body fat percentage was positively related with the exercise compliance (r = 0.34, P = 0.01). Exercise decreased truncal fat percentage and waist circumference, suggesting a reduction of central adiposity, but did not significantly affect body weight and BMI. Exercise significantly reduced serum low-density lipoprotein cholesterol (P = 0.037), which was positively correlated with decreases of truncal fat percentage (r = 0.222, P = 0.048). No significant effects of interventions on insulin sensitivity, early insulin release index, and aerobic fitness were observed., Conclusion: At least twice a week of one-hour after-school exercise significantly attenuated central adiposity and had a significant impact on lipid profiles in overweight Chinese adolescents.

Objective: To investigate the clinical significance of positive sputum culture for filamentous fungi., Methods: The medical data of 140 patients positive for filamentous fungi in sputum culture at Peking Union Medical College Hospital were reviewed retrospectively. Based on the diagnostic criteria by European Organization for Research and Treatment of Cancer/Mycoses Study Group, invasive pulmonary fungal infection (IPFI) was diagnosed. The clinical characteristics of cases with and without IPFI were analyzed respectively., Results: Among all 140 cases positive for filamentous fungi in sputum culture, only 22 cases could be diagnosed as IPFI. Two of 22 IPFI cases were confirmed by post-operative pathology, 1 case was confirmed by positive blood culture for filamentous fungi and the remaining 19 cases were diagnosed clinically according to the nature of hosts, characteristics of pulmonary infections and microbiological evidence (positive sputum culture for filamentous fungi, 2 - 5 times for each case). Most of etiological fungi in IPFI patients belonged to Aspergillus. And the identity of isolated fungal strain was mostly one strain for each patient. In IPFI group, patients who had been treated with broad-spectrum antibiotics (100%), steroids (13, 59.1%) or immunosuppressant (7, 31.8%) or who had pulmonary X-ray imaging changes (100%), primary diseases (21, 95.5%), hypoalbuminemia (18, 81.8%) or hemoptysis (10, 45.5%), were significantly more than those in non-IPFI group (66.9%, 34.7%, 18.6%, 79.7%, 72.0%, 45.8% and 4.2% respectively; P < 0.05 for each item). In IPFI group, itraconazole, amphotericin B and/or voriconazole were administrated, 8 patients (36.4%) were cured and 14 patients (63.6%) passed away. In non-IPFI group, the patients were treated with antibiotics, fluconazole, anti-tuberculosis, steroids or combined with immunosuppressant, chemotherapy or bronchoalveolar lavage; 96 cases (81.4%) were cured or showed improvement, and 22 cases (18.6%) died or gave up further treatment., Conclusions: The clinical significance of positive sputum culture for filamentous fungi are associated with the times of positive culture, the number and species of isolated fungal strains. Meanwhile it is important to determine whether there is IPFI according to the nature and clinical characteristics of patients.