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Viruses are dependent on the host factors for their replication and survival. Therefore, identification of host factors that druggable for antiviral development is crucial. The actin cytoskeleton plays an important role in the virus infection. The dynamics change of actin and its function are regulated by multiple actin-associated proteins (AAPs). However, the role and mechanism of various AAPs in the life cycle of virus are still enigmatic. In this study, we analyzed the roles of actin and AAPs in the replication of pseudorabies virus (PRV). Using a library of compounds targeting AAPs, our data found that multiple AAPs, such as Rho-GTPases, Rock, Myosin and Formin were involved in PRV infection. Besides, our result demonstrated that the actin-binding protein Drebrin was also participated in PRV infection. Further studies are necessary to elucidate the molecular mechanism of AAPs in the virus life cycle, in the hope of mining host factors for antiviral developments., 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 Inc. All rights reserved.)

As a highly promising treatment technology for wastewater, long start-up time is one of the bottlenecks hindering the widespread application of aerobic granular sludge (AGS). This study focused on exploring the possibility of alternating organic loading rate (OLR) in promoting AGS granulation. Under alternating OLR (3.6-14.4 kgCOD/m 3 ·d), AGS granulation was significantly accelerated. The mean granule size under alternating load reached 234.6 μm at 17 d, while under constant OLR (7.2 kgCOD/m 3 ·d), the mean granule size was only 179.2 μm. Moreover, the granule size maintained continuous growth even when the alternating OLR was changed to constant OLR. Alternating load significantly increased the content of extracellular polymeric substances (EPS), especially proteins (PN) in tightly bound EPS (TB-EPS), which was likely the main reason for accelerating AGS granulation. Moreover, alternating load reduced the hydrophilicity of EPS and promoted the content of proteins secondary structures that favored aggregation in TB-EPS, which were also beneficial for granulation. Microbial community results showed that alternating load might promote the enrichment of EPS producing bacteria, such as Thauera, Brevundimonas and Shinella. Meanwhile, the content of enzymes that regulated amino acids metabolism also increased under alternating load, which might be related to the increase of PN in EPS. These results further demonstrated that alternating load promoted granulation through EPS., 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 © 2023 Elsevier Ltd. All rights reserved.)

Background: Acute-on-chronic liver failure (ACLF) is a major challenge in the field of hepatology. While mesenchymal stem cell (MSC) therapy can improve the prognosis of patients with ACLF, the molecular mechanisms through which MSCs attenuate ACLF remain poorly understood. We performed global miRNA and mRNA expression profiling via next-generation sequencing of liver tissues from MSC-treated ACLF mice to identify important signaling pathways and major factors implicated in ACLF alleviation by MSCs., Methods: Carbon tetrachloride-induced ACLF mice were treated with saline or mouse bone marrow-derived MSCs. Mouse livers were subjected to miRNA and mRNA sequencing. Related signal transduction pathways were obtained through Gene Set Enrichment Analysis. Functional enrichment, protein-protein interaction, and immune infiltration analyses were performed for the differentially expressed miRNA target genes (DETs). Hub miRNA and mRNA associated with liver injury were analyzed using LASSO regression. The expression levels of hub genes were subjected to Pearson's correlation analysis and verified using RT-qPCR. The biological functions of hub genes were verified in vitro., Results: The tricarboxylic acid cycle and peroxisome proliferator-activated receptor pathways were activated in the MSC-treated groups. The proportions of liver-infiltrating NK resting cells, M2 macrophages, follicular helper T cells, and other immune cells were altered after MSC treatment. The expression levels of six miRNAs and 10 transcripts correlated with the degree of liver injury. miR-27a-5p was downregulated in the mouse liver after MSC treatment, while its target gene E2f2 was upregulated. miR-27a-5p inhibited E2F2 expression, suppressed G1/S phase transition and proliferation of hepatocytes, in addition to promoting their apoptosis., Conclusions: This is the first comprehensive analysis of miRNA and mRNA expression in the liver tissue of ACLF mice after MSC treatment. The results revealed global changes in hepatic pathways and immune subpopulations. The miR-27a-5p/E2F2 axis emerged as a central regulator of the MSC-induced attenuation of ACLF. The current findings improve our understanding of the molecular mechanisms through which MSCs alleviate ACLF., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023. Published by Elsevier Inc.)

Pleione is an orchid endemically distributed in high mountain areas across the Hengduan Mountains (HDM), Himalayas, Southeast Asia and South of China. The unique flower shapes, rich colors and immense medicinal importance of Pleione are valuable ornamental and economic resources. However, the phylogenetic relationships and evolutionary history of the genus have not yet been comprehensively resolved. Here, the evolutionary history of Pleione was investigated using single-copy gene single nucleotide polymorphisms and chloroplast genome datasets. The data revealed that Pleione could be divided into five clades. Discordance in topology between the two phylogenetic trees and network and D-statistic analyses indicated the occurrence of reticulate evolution in the genus. The evolution could be attributed to introgression and incomplete lineage sorting. Ancestral area reconstruction suggested that Pleione was originated from the HDM. Uplifting of the HDM drove rapid diversification by creating conditions favoring rapid speciation. This coincided with two periods of consolidation of the Asian monsoon climate, which caused the first rapid diversification of Pleione from 8.87 to 7.83 Mya, and a second rapid diversification started at around 4.05 Mya to Pleistocene. The interaction between Pleione and climate changes, especially the monsoons, led to the current distribution pattern and shaped the dormancy characteristic of the different clades. In addition to revealing the evolutionary relationship of Pleione with orogeny and climate changes, the findings of this study provide insights into the speciation and diversification mechanisms of plants in the East Asian flora., 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 © 2023 Fujian Agriculture and Forestry University. Published by Elsevier Inc. All rights reserved.)

Root knot nematodes are the most devastating root pathogens, causing severe damage and serious economic losses to agriculture worldwide. Octanoic acid has been reported as one of the nematicides, and its mode of action is not fully understood. The main objective of this study was to elucidate the effect of octanoic acid on Meloidogyne incognita by transcriptomic analysis combined with physiological and biochemical assays. In the toxicity assays with octanoic acid, the threshold concentration with nematicidal activity and the maximum concentration to which nematodes could respond were 0.03 μL/mL and 0.08 μL/mL respectively. Microscopic observation combined with protein and carbohydrates assays confirmed that the structure of the second-stage juveniles (J2s) was severely disrupted after 72 h of immersion in octanoic acid. Transcriptome analysis has shown that octanoic acid can interfere with the nematode energy metabolism, lifespan and signaling. Although the effects are multifaceted, the findings strongly point to the cuticle, lysosomes, and extracellular regions and spaces as the primary targets for octanoic acid. In addition, nematodes can withstand the negative effects of low concentration of octanoic acid to some extent by up-regulating the defense enzyme system and heterologous metabolic pathways. These findings will help us to explore the nematicidal mechanism of octanoic acid and provide important target genes for the development of new nematicides in the future., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023. Published by Elsevier Inc.)

The precise control of proliferation and differentiation of neural progenitors is crucial for the development of the central nervous system. Fused in sarcoma (FUS) is an RNA-binding protein pathogenetically linked to Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Lobar Degeneration (FTLD) disease, yet the function of FUS on neurodevelopment is remained to be defined. Here we report a pivotal role of FUS in regulating the human cortical brain and spinal cord development via the human iPSCs-derived organoids. We found that depletion of FUS via CRISPR/CAS9 leads to an enhancement of neural proliferation and differentiation in cortical brain-organoids, but intriguingly an impairment of these phenotypes in spinal cord-organoids. In addition, FUS binds to the mRNA of a Trk tyrosine kinase receptor of neurotrophin-3 (Ntrk3) and regulates the expression of the different isoforms of Ntrk3 in a tissue-specific manner. Finally, alleviated Ntrk3 level via shRNA rescued the effects of FUS-knockout on the development of the brain- and spinal cord-organoids, suggesting that Ntrk3 is involved in FUS-regulated organoids developmental changes. Our findings uncovered the role of FUS in the neurodevelopment of the human CNS., Competing Interests: Declaration of competing interest There is no potential conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Flumioxazin, a protoporphyrinogen oxidase (PPO; EC 1.3.3.4) inhibitor, has been used in soybean, cotton, grapes, and many other crops to control broad leaf weeds. Unfortunately, it can cause damage to cotton. To ameliorate phytotoxicity of flumioxazin to cotton, this work assessed the protective effects of diazabicyclo derivatives as potential safeners in cotton. A bioactivity assay proved that the phytotoxicity of flumioxazin on cotton was alleviated by some of the compounds. In particular, the activity of glutathione S-transferases (GSTs) was significantly enhanced by Compound 32, which showed good safening activity against flumioxazin injury. The physicochemical properties and absorption, distribution, metabolism, excretion and toxicity (ADMET) predictions proved that the pharmacokinetic properties of Compound 32 are similar to those of the commercial safener BAS 145138. The present work demonstrated that diazabicyclo derivatives are potentially efficacious as herbicide safeners, meriting further investigation., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Glaesserella parasuis (G. parasuis) is the pathogen of Glässer's disease in pig herds, which can cause severe inflammatory responses. However, at present, the pathogenic mechanism of G. parasuis is not very clear. LncRNAs can regulate the expression of mRNA in a variety of ways, thereby causing host cells to produce a variety of functional changes in response to bacterial infection. Here, we detected the changes in lncRNAs and mRNAs of 3D4/21 cells after G. parasuis CY1201 strain (serotype 13) infection. A total of 876 lncRNAs and 2166 mRNAs were differentially expression in 3D4/21 cells after G. parasuis infection. GO and KEGG enrichment analysis showed that the differentially up-regulated lncRNA target genes were mainly involved in the response to extracellular stimuli, cell receptor signaling pathways and chemokine signaling pathways. The differentially down-regulated lncRNA target genes were mainly involved in ERK1/ERK2 cascade reaction and adhesion junctions. 44 lncRNAs were screened that might be related in inflammation. CeRNA regulatory network of the top five difference inflammation-related lncRNAs showed that the up-regulated lncRNA group involved 5 lncRNAs, 50 miRNAs and 49 mRNAs. Meanwhile, there were 26 miRNAs and 36 mRNAs in the top five down-regulated lncRNA group. Our results contribute to understand the basic role of lncRNAs in 3D4/21 cells during G. parasuis infection, and lay the foundation for following research., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

4-Hydroxyphenylpyruvate dioxygenase (HPPD) is an important target for herbicide design. A multilayered virtual screening workflow was constructed by combining two pharmacophore models based on ligand and crystal complexes, molecular docking, molecular dynamics (MD), and biological activity determination to identify novel small-molecule inhibitors of HPPD. About 110, 000 compounds of Bailingwei and traditional Chinese medicine databases were screened. Of these, 333 were analyzed through docking experiments. Five compounds were selected by analyzing the binding pattern of inhibitors with amino acid residues in the active pocket. All five compounds could produce stable coordination with cobalt ion, and form favorable π-π interactions. MD simulation demonstrated that Phe381 and Phe424 made large contributions to the strength of binding. The enzyme activity experiment verified that compound-139 displayed excellent potency against AtHPPD (IC 50  = 0.742 μM), however, compound-5222 had inhibitory effect on human HPPD (IC 50  = 6 nM). Compound-139 exhibited herbicidal activity to some extent on different gramineous weeds. This work provided a strong insight into the design and development of novel HPPD inhibitor using in silico techniques., (Copyright © 2022 Elsevier Inc. All rights reserved.)

We aim to establish a comprehensive COVID-19 autoantigen atlas in order to understand autoimmune diseases caused by SARS-CoV-2 infection. Based on the unique affinity between dermatan sulfate and autoantigens, we identified 348 proteins from human lung A549 cells, of which 198 are known targets of autoantibodies. Comparison with current COVID data identified 291 proteins that are altered at protein or transcript level in SARS-CoV-2 infection, with 191 being known autoantigens. These known and putative autoantigens are significantly associated with viral replication and trafficking processes, including gene expression, ribonucleoprotein biogenesis, mRNA metabolism, translation, vesicle and vesicle-mediated transport, and apoptosis. They are also associated with cytoskeleton, platelet degranulation, IL-12 signaling, and smooth muscle contraction. Host proteins that interact with and that are perturbed by viral proteins are a major source of autoantigens. Orf3 induces the largest number of protein alterations, Orf9 affects the mitochondrial ribosome, and they and E, M, N, and Nsp proteins affect protein localization to membrane, immune responses, and apoptosis. Phosphorylation and ubiquitination alterations by viral infection define major molecular changes in autoantigen origination. This study provides a large list of autoantigens as well as new targets for future investigation, e.g., UBA1, UCHL1, USP7, CDK11A, PRKDC, PLD3, PSAT1, RAB1A, SLC2A1, platelet activating factor acetylhydrolase, and mitochondrial ribosomal proteins. This study illustrates how viral infection can modify host cellular proteins extensively, yield diverse autoantigens, and trigger a myriad of autoimmune sequelae. Our work provides a rich resource for studies into "long COVID" and related autoimmune sequelae., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Carotenoids are an important source of metabolites with regulatory function, which include the plant hormones abscisic acid (ABA) and strigolactones (SLs), and several recently identified growth regulators and signaling molecules. These carotenoid-derivatives originate from oxidative breakdown of double bonds in the carotenoid polyene, a common metabolic process that gives rise to diverse carbonyl cleavage-products known as apocarotenoids. Apocarotenoids exert biologically important functions in all taxa. In plants, they are a major regulator of plant growth, development and response to biotic and abiotic environmental stimuli, and mediate plant's communication with surrounding organisms. In this article, we provide a general overview on the biology of plant apocarotenoids, focusing on ABA, SLs, and recently identified apocarotenoid growth regulators. Following an introduction on carotenoids, we describe plant apocarotenoid biosynthesis, signal transduction, and evolution and summarize their biological functions. Moreover, we discuss the evolution of these intriguing metabolites, which has not been adequately addressed in the literature., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Gallibacterium anatis (G. anatis), one of the major pathogens causing reproductive tract disorders in laying hens, leads to a reduction in egg production and increased mortality, caused by either single or mixed infections with other pathogens. As a specific virulence factor of G. anatis, the role of GtxA in layers' salpingitis remains unclear. In this study, we explored the effect of GtxA on G. anatis infection by comparing wild strain Yu-PDS-RZ-1-SLG (RZ) and its GtxA deleted counterpart RZΔgtxA in primary chicken oviduct epithelial cells (COEC). Their adherence, invasion, cytoxicity, and ability to induce apoptosis and and cytokine secretion were evaluated and the cytotoxicity and cytokine secretion of the recombinant GtxA protein and its N-terminal adenylate cyclase and C-terminal RTX hemolysin domain were also analyzed. We found that the adhesion ability of RZΔgtxA was significantly lower than that of parental strain RZ, and its toxicity to COEC was weakened; Meanwhile, apoptosis was inhibited and the expression of IL-6, IL-2, TNF-α and IFN-γ were dramatically reduced in COEC infected by RZΔgtxA. In contrast, the recombinant protein GtxA inhibited the proliferation of oviduct cells and induced obvious cytotoxicity, and the expression of IL-6, TNF-α and IFN-γ were up-regulated in COEC interacted with recombinant proteins. Our study indicates that GtxA promotes G. anatis adherence to cells, changes cells permeability and expression of inflammatory factors, resulting in cell damage and apoptosis., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Ganglioneuritis was the primary pathologic change in infected abalone associated with Haliotid herpesvirus 1 (HaHV-1) infection, which eventually became known as abalone viral ganglioneuritis (AVG). However, the distribution of HaHV-1 in the other tissues and organs of infected abalone has not been systemically investigated. In the present study, the distribution of HaHV-1-CN2003 variant in different organs of small abalone, Haliotis diversicolor supertexta, collected at seven different time points post experimental infection, was investigated with histopathological examination and in situ hybridization (ISH) of HaHV-1 DNA. ISH signals were first observed in pedal ganglia at 48 h post injection, and were consistently observed in this tissue of challenged abalone. At the same time, increased cellularity accompanied by ISH signals was observed in some peripheral ganglia of mantle and kidney. At the end of infection period, lesions and co-localized ISH signals in infiltrated cells were detected occasionally in the mantle and hepatopancreas. Transmission electron microscope analysis revealed the presence of herpes-like viral particles in haemocyte nuclei of infected abalone. Our results indicated that, although HaHV-1-CN2003 was primarily neurotropic, it could infect other tissues including haemocytes., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Chelerythrine (CHE) possesses broad pharmacological activities. In this study, the extract of Chelidonium majus L. were characterized by high performance liquid chromatography (HPLC), infrared radiation (IR) spectroscopy and nuclear magnetic resonance (NMR). It was proved that the extract was CHE. The antifungal activity of CHE against five fungal pathogens of rice was researched in vitro, revealing that CHE inhibited Ustilaginoidea virens (U. virens) and Cochliobolus miyabeanus (C. miyabeanus) with 50% effective concentrations (EC 50 ) of 6.53 × 10 -3  mg/mL and 5.62 × 10 -3  mg/mL, respectively. When the concentration of CHE was 7.5 × 10 -3  mg/mL, the inhibition rate of U. virens reached 56.1%. Moreover, CHE (4 × 10 -3  mg/mL) exhibited the greatest efficacy in inhibiting spore of U. virens growth with an inhibition rate as high as 86.7%. CHE displayed the best inhibitory activity against U. virens at the concentration of 7.5 × 10 -3  mg/mL, compared with the other two isoquinoline alkaloids and commercial fungicide validamycin. After treating U. virens mycelia with CHE, twisted and atrophied mycelia were observed by optical microscopy. SEM results demonstrated narrow and locally fractured mycelium. TEM observations showed that the cell wall had become thin and broken, and most organelles were difficult to recognize. Furthermore, membrane of mycelia was destroyed and reactive oxygen species (ROS) of spores was accumulated, which induced apoptosis of pathogenic fungi. From these results, our understanding of the mechanisms of antifungal activity of CHE against U. virens was enriched and this research is relevant for developing novel pesticides., Competing Interests: Declaration of Competing interest The authors declare no competing financial interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Traumatic brain injury (TBI) is one of the most common causes of death and disability worldwide. We investigated whether inhibition of p53 using pifithrin (PFT)-α or PFT-μ provides neuroprotective effects via p53 transcriptional dependent or -independent mechanisms, respectively. Sprague Dawley rats were subjected to controlled cortical impact TBI followed by the administration of PFTα or PFT-μ (2 mg/kg, i.v.) at 5 h after TBI. Brain contusion volume, as well as sensory and motor functions were evaluated at 24 h after TBI. TBI-induced impairments were mitigated by both PFT-α and PFT-μ. Fluoro-Jade C staining was used to label degenerating neurons within the TBI-induced cortical contusion region that, together with Annexin V positive neurons, were reduced by PFT-μ. Double immunofluorescence staining similarly demonstrated that PFT-μ significantly increased HO-1 positive neurons and mRNA expression in the cortical contusion region as well as decreased numbers of 4-hydroxynonenal (4HNE)-positive cells. Levels of mRNA encoding for p53, autophagy, mitophagy, anti-oxidant, anti-inflammatory related genes and proteins were measured by RT-qPCR and immunohistochemical staining, respectively. PFT-α, but not PFT-μ, significantly lowered p53 mRNA expression. Both PFT-α and PFT-μ lowered TBI-induced pro-inflammatory cytokines (IL-1β and IL-6) mRNA levels as well as TBI-induced autophagic marker localization (LC3 and p62). Finally, treatment with PFT-μ mitigated TBI-induced declines in mRNA levels of PINK-1 and SOD2. Our data suggest that both PFT-μ and PFT-α provide neuroprotective actions through regulation of oxidative stress, neuroinflammation, autophagy, and mitophagy mechanisms, and that PFT-μ, in particular, holds promise as a TBI treatment strategy., (Copyright © 2019. Published by Elsevier Inc.)

Visceral leishmaniasis (VL) caused by Leishmania spp. is an important vector-borne disease prevalent in China. VL was rampant in the vast area of China north of the Yangtze River before the founding of the People's Republic of China in 1949. As a result of strenuous interventions, the disease was basically eliminated in most of the former epidemic areas in 1958-60. At present, only sporadic cases occur in the western regions of China. In the process, National Institute of Parasitic Diseases at China CDC and the Chinese Center for Tropical Diseases Research (NIPD-CTDR) have achieved great impact in controlling the diseases as well as in research on Leishmania spp. This review summarized the contribution of experts from NIPD-CTDR to the control and elimination of VL in various aspects, such as understanding the epidemiological features of VL, confirmation of VL vectors and their distribution, development of control tools including diagnostics and insecticides, monitoring and evaluation supported by information management, technical supports to the control programmes, as well as analysis of the challenges faced. At the same time, it puts forward constructive suggestions for the ultimate interruption of VL transmission in China., (© 2020 Elsevier Ltd. All rights reserved.)

Background: The impact of dual-ring wound protectors (DRWPs) on the long-term outcomes of patients with colorectal cancer (CRC) undergoing elective surgery remains unclear. The aim of this cohort study was to compare short- and long-term outcomes after CRC resection with or without use of a DRWP., Methods: This study enrolled 625 patients with stage I-III CRC undergoing curative resection and divided them into DRWP (n = 348) and control (n = 277) groups. Primary endpoints were postoperative short- and long-term complications. Secondary endpoints were oncological outcomes including wound recurrence, disease-free survival, and overall survival., Results: Rates of postoperative complications (P = 0.004) and laparotomy wound infection (LWI) (P < 0.001) were markedly lower in the DRWP group. Operation quality, as per the number of lymph nodes harvested and rate of R0 resection, did not differ between the groups (all P > 0.05). The DRWP group exhibited significantly lower rates of incisional hernia occurrence (5.3% versus 9.5%, P = 0.045) compared with the control group. Multivariable analyses demonstrated an increased risk of LWI with no wound protector in colorectal surgery (odds ratio, 3.778; P = 0.001), and patients who developed LWI after surgery were more than 4 times more likely to develop an incisional hernia during outpatient follow-up (odds ratio, 4.333; P = 0.001). One patient in the control group (0.36%) had isolated wound recurrence at 12 mo postoperatively., Conclusions: Fewer postoperative and late complications, comparable oncological safety, and similar long-term clinical outcomes confirmed the benefits of DRWP use for patients with CRC undergoing elective surgery. Therefore, the use of DRWP may be considered in curative CRC resection., (Copyright © 2019 Elsevier Inc. All rights reserved.)

γδ T cells are a unique population of lymphocytes that have regulatory roles in patients with chronic hepatitis B (CHB); however, their role in acute hepatitis B (AHB) infection remains unclear. Phenotype and function of γδ T cells were analyzed in 29 AHB patients, 28 CHB patients, and 30 healthy controls (HCs) using immunofunctional assays. Compared with HCs and CHB patients, decreased peripheral and increased hepatic γδ T cells were found in AHB patients. Increased hepatic γδ T cells in AHB patients were attributed to elevated hepatic chemokine levels. Peripheral γδ T cells exhibited highly activated and terminally differentiated memory phenotype in AHB patients. Consistently, peripheral γδ T cells in AHB patients showed increased cytotoxic capacity and enhanced antiviral activity which was further proved in longitudinal study. Activated γδ T cells in AHB patients exhibited increased cytotoxicity and capacity for viral clearance associated with liver injury and the control of infection., (Copyright © 2019 Elsevier Inc. All rights reserved.)

With increasing demand for biodiesel, crude glycerol as a by-product in biodiesel production has been generated and oversupplied. This study, therefore, explored the pretreatment and a subsequent two-stage microbial system to convert crude glycerol into high value-added products: 1,3-propanediol (1,3-PDO) and polyhydroxyalkanoates (PHAs). After pretreatment, long chain fatty acids (LCFAs) could be effectively removed from crude glycerol to eliminate the inhibition effects on subsequent microbial process. In the anaerobic fermentation, when fed treated crude glycerol increased from 20 g/L to 100 g/L, 1,3-PDO yield decreased from 0.438 g/g to 0.345 g/g and accompanied carboxylic acids shifted from acetate and lactate dominant to lactate overwhelmingly dominant. Meanwhile, the relative abundance of Clostridiales sustained around 50% but Enterobacteriales increased from 19% to 53%. Further fed glycerol increase to 140 g/L resulted in severe substrate inhibition, which could be relieved by intermittent feeding. In aerobic process, glycerol anaerobic digestion effluent (ADE) was fed to the consortium of Bacillus megaterium and Corynebacterium hydrocarbooxydans for selectively consumption of carboxylic acids and residual glycerol from 1,3-PDO to produce PHAs as a secondary high value-added product. The consortium accumulated maximum 8.0 g/L poly (3-hydroxybutyrate) (PHB), and 1,3-PDO purity increased from initial 27.7% to almost 100% when fed with 100 g/L glycerol ADE. Overall, this study provided comprehensive and insightful information on microbial conversion of crude glycerol to high value-added products after pretreatment., (Copyright © 2018. Published by Elsevier Ltd.)

Abalone viral ganglioneuritis (AVG), caused by Haliotid herpesvirus-1 (HaHV-1) infection, has been reported as the main cause of mortality and heavy losses of wild and cultivated abalone in Taiwan and Australia since 2003. HaHV-1 DNA has also been reported in diseased abalone collected in early 2000s in China. However, no data is available about the susceptibility, disease process and pathological changes of HaHV-1 infection in the primary cultivated abalone species in China. In the present study, two cultivated abalone species, Haliotis diversicolor supertexta and Haliotis discus hannai, were challenged with HaHV-1-CN2003 collected in 2003 in China using three different methods. Results showed that H. diversicolor supertexta was highly susceptible to HaHV-1-CN2003 infection and suffered acute mortality using all three challenge methods. H. discus hannai was not susceptible to the viral infection. Histopathology combined with transmission electron microscopy and quantitative PCR analysis revealed that the tropism of HaHV-1-CN2003 includes both neural tissue and haemocytes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Orosomucoid like-3 (ORMDL3) has been identified to be associated with the development of asthma according to previous studies. However, the definite role of ORMDL3 in the pathogenesis of asthma remains unclear. In this study, we found ORMDL3 was highly expressed in PBMC specimens from childhood asthma patients. Cytokines production and p-ERK/MMP-9 pathway expression was also increased in childhood asthma patients compared with controls. In addition, ORMDL3 overexpression induced IL-6 and IL-8 release and activated p-ERK/MMP-9 pathway in vitro. Increased ORMDL3 expression was observed after treated with 5-Aza-CdR. 5-Aza-CdR decreased the percentage of the CpG island in the ORMDL3 promoter region and increased its promoter activity. In addition, 5-Aza-CdR significantly increased IL-6 and IL-8 levels in NHBE cells while there was no obvious alteration after knocking down ORMDL3. Knockdown of ORMDL3 also significantly decreased the expression of p-ERK/MMP-9 pathway in the presence or absence of 5-Aza-CdR. In conclusion, our study provided novel evidence for the association between ORMDL3 and asthma-associated cytokines. Moreover, DNA methylation plays an important role in ORMDL3-mediated increased IL-6 and IL-8 levels and p-ERK/MMP-9 pathway expression., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Orosomucoid 1-like protein 3 (ORMDL3) is an asthma candidate gene associated with virus-triggered recurrent wheeze. Stimulator of interferon gene (STING) controls TLR-independent cytosolic responses to viruses. However, the association of STING with ORMDL3 is unclear. Here, we have shown that ORMDL3 expression shows a linear correlation with STING in recurrent wheeze patients. In elucidating the molecular mechanisms of the ORMDL3-STING relationship, we found that STING promoted the transcriptional activity of ORMDL3, which was significantly associated with increased levels of interferon regulatory factor 3 (IRF3) and signal transducer and activator of transcription 6 (STAT6). Further study showed that via activation of TANK binding kinase 1 (TBK1), STING enhanced the phosphorylation and binding of IRF3 and STAT6, which upregulated ORMDL3 by binding to the promoter. Our results showed that STING positively regulated ORMDL3 through the TBK1-IRF3-STAT6 complex., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Cardiac fibrosis is characterized by excessive deposition of extracellular matrix (ECM) proteins in the myocardium and results in decreased ventricular compliance and diastolic dysfunction. Cartilage intermediate layer protein-1 (CILP-1), a novel identified cardiac matricellular protein, is upregulated in most conditions associated with cardiac remodeling, however, whether CILP-1 is involved in pressure overload-induced fibrotic response is unknown. Here, we investigated whether CILP-1 was critically involved in the fibrotic remodeling induced by pressure overload. Western blot analysis and immunofluorescence staining showed that CILP-1 was predominantly detected in cardiac myocytes and to a less extent in the interstitium. In isolated adult mouse ventricular myocytes and nonmyocytes, CILP-1 was found to be mainly synthesized by myocytes. CILP-1 expression in left ventricles was upregulated in C57BL/6 mice undergoing transverse aortic constriction (TAC). Myocardial CILP-1 knockdown aggravated whereas CILP-1 overexpression attenuated TAC-induced ventricular remodeling and dysfunction, as measured by echocardiography test, morphological examination, and gene expressions of fibrotic molecules. Incubation of cardiac fibroblasts with the conditioned medium containing full-length, N-terminal, or C-terminal CILP-1 inhibited transforming growth factor (TGF)-β1-induced Smad3 phosphorylation and the subsequent profibrotic events. We first demonstrated that C-terminal CILP-1 increased Akt phosphorylation, promoted the interaction between Akt and Smad3, and suppressed Smad3 phosphorylation. Blockade of PI3K-Akt pathway attenuated the inhibitory effect of C-CILP-1 on TGF-β1-induced Smad3 activation. We conclude that CILP-1 is a novel ECM protein possessing anti-fibrotic ability in pressure overload-induced fibrotic remodeling. This anti-fibrotic effect of CILP-1 attributes to interfering TGF-β1 signaling through its N- and C- terminal fragments., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

We previously reported that interleukin-6 (IL-6) in the red nucleus (RN) is up-regulated at 3weeks after spared nerve injury (SNI), and plays facilitated role in the later maintenance of neuropathic pain. The current study aimed to reveal the roles of different signaling pathways, including Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3), extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK) and phosphatidylinositide 3-kinase/protein kinase B (PI3K/AKT), in RN IL-6-mediated pain modulation. In accord with the increase of IL-6 in the RN following SNI, the protein levels of phospho-STAT3 (p-STAT3), p-ERK and p-JNK were also up-regulated in the RN contralateral to the nerve injury side at 3weeks after SNI. The increases of p-STAT3 and p-ERK (but not p-JNK) were associated with IL-6 and could be blocked by anti-IL-6 antibody. Microinjection of JAK2 inhibitor AG490, ERK inhibitor PD98059 and also JNK inhibitor SP600125 into the RN significantly increased the paw withdrawal threshold (PWT) and alleviated SNI-induced mechanical allodynia. Further studies showed that microinjection of recombinant rat IL-6 (rrIL-6, 20ng) into the RN of normal rats significantly decreased the PWT of rats and increased the local protein levels of p-STAT3 and p-ERK, but not p-JNK. Pre-treatment with AG490 and PD98059 could prevent IL-6-induced mechanical allodynia. Whereas, p-p38 MAPK and p-AKT did not show any expression changes in the RN of rats with SNI or rats treated with rrIL-6. These results suggest that RN IL-6 participates in the later maintenance of SNI-induced neuropathic pain and plays facilitated role through activating JAK/STAT3 and ERK signaling pathways., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: With the recent development of molecular markers, strategies for identifying patients with colorectal cancer (CRC) having a high risk of postoperative early relapse (within 1 y) and relapse have been improved. We previously constructed a multigene biochip with 19 candidate genes. The objective of the present study was to optimize a multigene biochip for detecting the risk of postoperative early relapse and relapse in patients with CRC., Methods: We included 357 patients with stage I-III CRC who underwent curative resection at a single institution between June 2010 and May 2015. During each follow-up, a postoperative surveillance strategy including the National Comprehensive Cancer Network recommendations and a multigene biochip was used. A statistical algorithm was developed to select candidate biomarkers for an optimal combination., Results: After a 30.9-mo median follow-up, 67 patients (18.8%) had postoperative relapse, of whom 25 (7.0%) relapsed within 1 y after operation and accounted for 37.3% of all relapsed patients. Of the 19 circulating biomarkers, ELAVL4, PTTG1, BIRC5, PDE6D, CHRNB1, MMP13, and PSG2, which presented significant predictive validity, were selected for combination. The expression of the seven-biomarker biochip resulted in area under the receiver operating characteristic curve values of 0.854 (95% confidence interval: 0.756-0.952) for early relapse and 0.884 (95% confidence interval: 0.830-0.939) for relapse. Moreover, the sensitivity, specificity, and predictive accuracy levels were 84.0%, 83.1%, and 83.2% for early relapse and 76.1%, 91.0%, and 88.2% for relapse (P = 0.415, 0.006, and 0.054, respectively). The median lead times before the detection of postoperative early relapse and relapse were 3.8 and 10.4 mo, respectively., Conclusions: From 19 circulating biomarkers, we optimized seven contemporary circulating biomarkers. The prediction model used for the early and accurate identification of Taiwanese patients with CRC having a high risk of postoperative early relapse and relapse seems to be feasible and comparable., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Patients with rheumatoid arthritis (RA) exhibit an increased risk of dementia. Disease-modifying antirheumatic drugs (DMARDs) are commonly used to slow RA progression, but studies investigating the relationship between DMARDs and dementia in patients with RA are lacking. We investigated the relationship between DMARDs and dementia in patients with RA., Methods: Using the National Health Insurance Research Database, patients aged ≥20years, who were newly diagnosed with RA between 2000 and 2011 were identified. Patients with RA who had dementia comprised the dementia group, and patients with RA who did not have dementia comprised the control group. The groups were matched at a 1:1 ratio by the propensity score. DMARDs were categorized into conventional synthetic DMARDs (csDMARDs) and biological DMARDs (bDMARDs). Logistic regression models were used to calculate the odds ratio and 95% confidence interval (CI) to evaluate the association between DMARD use and the risk of dementia in patients with RA., Results: A total of 957 patients with RA and dementia, and 957 patients with RA but not dementia, were enrolled. The risk of dementia was determined to be 1.63-fold higher in patients with RA with csDMARD use than in those without csDMARD use (95% CI=1.33-2.00). No significant risk of dementia was observed in patients with RA who used bDMARDs compared with their counterparts. However, patients with RA who used hydroxychloroquine, methotrexate, and sulfasalazine exhibited significant risks of dementia, irrespective of cumulative exposure days., Conclusion: Patients with RA who used csDMARDs exhibit significant association with dementia., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Th17 cells are involved in liver fibrosis by activating hepatic stellate cells (HSCs). We aimed to investigate whether HSCs are able to regulate the function of Th17 cells and to determine the relevant mechanism. Sixty-five patients diagnosed with chronic hepatitis B (CHB) were enrolled in this study. To determine the effect of HSCs on T cells, naïve CD4 + T cells and Th17 cells were sorted from CHB patients and cultured with or without activated-HSCs, and cytokine expression and gene transcription were analyzed. In addition, the regulatory mechanism of HSCs was investigated. ELISA and qRT-PCR showed that Th17 cells from CHB patients were more pathogenic, on the basis of the expression of IL-17A, IL-23R, RORC, CCL20 and CCR6, and meanwhile, they could activate the primary HSCs. Co-culture experiments indicated that activated HSCs dramatically promoted proliferation of CD4 + T cells in a time- and dose-dependent manner. In addition, they could induce naïve CD4 + T cells to become Th17 cells which had a more pathogenic phenotype. Moreover, activated HSCs-mediated induction of Th17 cells might depend on the release of IL-1β and IL-6 as well as on the COX-PGE2 pathway. Th17 cells cooperated with HSCs in a proinflammatory feedback loop might provide a better understanding of the pathogenic role of Th17 cells in the chronicity of HBV infection., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Neuronal apoptosis in the hippocampus has been detected after TBI. The hippocampal dysfunction may result in cognitive deficits in learning, memory, and spatial information processing. Our previous studies demonstrated that a p53 inhibitor, pifithrin-α oxygen analogue (PFT-α (O)), significantly reduced cortical cell death, which is substantial following controlled cortical impact (CCI) TBI, and improved neurological functional outcomes via anti-apoptotic mechanisms. In the present study, we examined the effect of PFT-α (O) on CCI TBI-induced hippocampal cellular pathophysiology in light of this brain region's role in memory. To investigate whether p53-dependent apoptosis plays a role in hippocampal neuronal loss and associated cognitive deficits and to define underlying mechanisms, SD rats were subjected to experimental CCI TBI followed by the administration of PFT-α or PFT-α (O) (2mg/kg, i.v.) or vehicle at 5h after TBI. Magnetic resonance imaging (MRI) scans were acquired at 24h and 7days post-injury to assess evolving structural hippocampal damage. Fluoro-Jade C was used to stain hippocampal sub-regions, including CA1 and dentate gyrus (DG), for cellular degeneration. Neurological functions, including motor and recognition memory, were assessed by behavioral tests at 7days post injury. p53, p53 upregulated modulator of apoptosis (PUMA), 4-hydroxynonenal (4-HNE), cyclooxygenase-IV (COX IV), annexin V and NeuN were visualized by double immunofluorescence staining with cell-specific markers. Levels of mRNA encoding for caspase-3, p53, PUMA, Bcl-2, Bcl-2-associated X protein (BAX) and superoxide dismutase (SOD) were measured by RT-qPCR. Our results showed that post-injury administration of PFT-α and, particularly, PFT-α (O) at 5h dramatically reduced injury volumes in the ipsilateral hippocampus, improved motor outcomes, and ameliorated cognitive deficits at 7days after TBI, as evaluated by novel object recognition and open-field test. PFT-α and especially PFT-α (O) significantly reduced the number of FJC-positive cells in hippocampus CA1 and DG subregions, versus vehicle treatment, and significantly decreased caspase-3 and PUMA mRNA expression. PFT-α (O), but not PFT-α, treatment significantly lowered p53 and elevated SOD2 mRNA expression. Double immunofluorescence staining demonstrated that PFT-α (O) treatment decreased p53, annexin V and 4-HNE positive neurons in the hippocampal CA1 region. Furthermore, PUMA co-localization with the mitochondrial maker COX IV, and the upregulation of PUMA were inhibited by PFT-α (O) after TBI. Our data suggest that PFT-α and especially PFT-α (O) significantly reduce hippocampal neuronal degeneration, and ameliorate neurological and cognitive deficits in vivo via antiapoptotic and antioxidative properties., (Copyright © 2016. Published by Elsevier Inc.)

C1q/tumor necrosis factor-related protein-3 (CTRP3) is an adipokine with modulation effects on metabolism and inflammation. Adenosine triphosphate (ATP) exerts multiple biological effects in vascular smooth muscle cells (VSMCs) and energy imbalance is involved in vascular diseases. This study aimed to explore the effect of CTRP3 on energy production and its underlying mechanism in VSMCs. Our results indicated that exogenous CTRP3 increased ATP synthesis and the protein expression of oxidative phosphorylation (OXPHOS)-related molecules, including peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α, sirtuin-3 (SIRT3), complex I, II, III, and V in cultured VSMCs. Depletion of endogenous CTRP3 by small interfering RNA (siRNA) reduced ATP synthesis and the expression of those molecules. PGC-1α knockdown abrogated CTRP3-induced ATP production and OXPHOS-related protein expression. Furthermore, CTRP3 increased mitochondrial reactive oxygen species (ROS) production and mitochondrial membrane potential level. Pretreatment with N-acetyl-L-cysteine, a reactive oxygen species scavenger, and cyanidem-chlorophenylhydrazone, an uncoupler of OXPHOS, suppressed CTRP3-induced ROS production, PGC-1α expression and ATP synthesis. In conclusion, CTRP3 modulates mitochondrial energy production through targets of ROS and PGC-1α in VSMCs., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The humpback dolphins of the eastern Taiwan Strait were first discovered scientifically in 2002 and since then have received much research attention. We reviewed all information published in peer-reviewed scientific journals on these dolphins and where appropriate and available, peer-reviewed scientific workshop reports and graduate theses were also examined. Recent evidence demonstrated that this population warranted recognition as a subspecies, Sousa chinensis taiwanensis. It is found in a highly restricted and linear strip of coastal waters along central western Taiwan. Numbering fewer than 80 individuals and declining, five main threats (fisheries interactions, habitat loss and degradation, loss of freshwater to estuaries within their habitat, air and water pollution, and noise) threaten the future existence of this subspecies. These dolphins have cultural and religious importance and boast the highest level of legal protection for wildlife in Taiwan. However, despite enormous efforts by local and international non-governmental groups urging immediate conservation actions, there have been no real government efforts to mitigate any existing threats; instead, some of these threats have worsened. Based on recent studies, we suggest the IUCN Red List status be revised to Critically Endangered CR 2a(ii); D for the subspecies., (© 2016 Elsevier Ltd. All rights reserved.)

As an edible traditional Chinese herb, Fructus psoraleae (FP) has been widely used in Asia for the treatment of vitiligo, bone fracture and osteoporosis. Several cases on markedly elevated bilirubin and acute liver injury following administration of FP and its related proprietary medicine have been reported, but the mechanism in FP-associated toxicity has not been well investigated yet. This study aimed to investigate the inhibitory effects of FP extract and its major constituents against human UDP-glucuronosyltransferase 1A1 (UGT1A1), the key enzyme responsible for metabolic elimination of bilirubin. To this end, N-(3-carboxy propyl)-4-hydroxy-1,8-naphthalimide (NCHN), a newly developed specific fluorescent probe for UGT1A1, was used to evaluate the inhibitory effects of FP extract or its fractions in human liver microsomes (HLM), while LC-UV fingerprint and UGT1A1 inhibition profile were combined to identity and characterize the naturally occurring inhibitors of UGT1A1 in FP. Our results demonstrated that both the extract of FP and five major components of FP displayed evident inhibitory effects on UGT1A1 in HLM. Among these five identified naturally occurring inhibitors, bavachin and corylifol A were found to be strong inhibitors of UGT1A1 with the inhibition kinetic parameters (Ki) values lower than 1 μM, while neobavaisoflavone, isobavachalcone, and bavachinin displayed moderate inhibitory effects against UGT1A1 in HLM, with the Ki values ranging from 1.61 to 9.86μM. These findings suggested that FP contains natural compounds with potent inhibitory effects against human UGT1A1, which may be one of the important reasons for triggering FP-associated toxicity, including elevated bilirubin levels and liver injury., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Programmed death of neuronal cells plays a crucial role in acute and chronic neurodegeneration following TBI. The tumor suppressor protein p53, a transcription factor, has been recognized as an important regulator of apoptotic neuronal death. The p53 inactivator pifithrin-α (PFT-α) has been shown to be neuroprotective against stroke. A previous cellular study indicated that PFT-α oxygen analog (PFT-α (O)) is more stable and active than PFT-α. We aimed to investigate whether inhibition of p53 using PFT-α or PFT-α (O) would be a potential neuroprotective strategy for TBI. To evaluate whether these drugs protect against excitotoxicity in vitro, primary rat cortical cultures were challenged with glutamate (50mM) in the presence or absence of various concentrations of the p53 inhibitors PFT-α or PFT-α (O). Cell viability was estimated by LDH assay. In vivo, adult Sprague Dawley rats were subjected to controlled cortical impact (CCI, with 4m/s velocity, 2mm deformation). Five hours after injury, PFT-α or PFT-α (O) (2mg/kg, i.v.) was administered to animals. Sensory and motor functions were evaluated by behavioral tests at 24h after TBI. The p53-positive neurons were identified by double staining with cell-specific markers. Levels of mRNA encoding for p53-regulated genes (BAX, PUMA, Bcl-2 and p21) were measured by reverse transcription followed by real time-PCR from TBI animals without or with PFT-α/PFT-α (O) treatment. We found that PFT-α(O) (10 μM) enhanced neuronal survival against glutamate-induced cytotoxicity in vitro more effectively than PFT-α (10 μM). In vivo PFT-α (O) treatment enhanced functional recovery and decreased contusion volume at 24h post-injury. Neuroprotection by PFT-α (O) treatment also reduced p53-positive neurons in the cortical contusion region. In addition, p53-regulated PUMA mRNA levels at 8h were significantly reduced by PFT-α (O) administration after TBI. PFT-α (O) treatment also decreased phospho-p53 positive neurons in the cortical contusion region. Our data suggest that PFT-α (O) provided a significant reduction of cortical cell death and protected neurons from glutamate-induced excitotoxicity in vitro, as well as improved neurological functional outcome and reduced brain injury in vivo via anti-apoptotic mechanisms. The inhibition of p53-induced apoptosis by PFT-α (O) provides a useful tool to evaluate reversible apoptotic mechanisms and may develop into a novel therapeutic strategy for TBI., Competing Interests: Financial Disclosure No competing financial interest exists. Conflict of interest The authors have no conflicts of interest relevant to this article to disclose., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The susceptibility of the host to influenza virus is determined by the distribution of the sialic acid (SA) receptors on host cell membrane. Avian influenza virus (AIV) preferentially binds to SA α-2,3-galactose (SA α2,3-gal) linked receptors, while human strains bind to sialic acid α2,6-galactose (SA α2,6-gal) linked receptors. Here, we describe the SA patterns and distributions in the reproductive tract of hens by employing two specific lectins, Maackia amurensis agglutinin (MAA) for SA α2,3-gal and sambucus nigra agglutinin (SNA) for SA α 2,6-gal receptors. Our results revealed that both SA α2,3-gal and SA α2,6-gal receptors exist in the reproductive tract of hens, including magnum, isthmus, uterus and vagina except for infundibulum. The distribution of SAα-2,3-gal receptor was more abundantly in the columnar epithelium cells of magnum, isthmus and uterus. Only minimal positive results for SA α-2,6-gal receptors were detected in the columnar epithelium cells of magnum, isthmus, uterus and vagina. Furthermore, AIV in tissues of the reproductive tract tissues of laying hens were detected by SYBR green-based reverse transcription and polymerase chain reaction (RT-PCR). Results showed that both viral loads and pathological changes in different parts of the reproductive tract were positively correlated with the expression of both receptors. Our results revealed that the reproductive tract of hens may provide an environment for the replication of both avian and human influenza viruses., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Adenosine deaminases that act on RNA (ADARs) have been reported to be functional on various viruses. ADAR1 may exhibit antiviral or proviral activity depending on the type of virus. Human immunodeficiency virus (HIV)-1 is the most well-studied lentivirus with respect to its interaction with ADAR1, and variable results have been reported. In this study, we demonstrated that equine ADAR1 (eADAR1) was a positive regulator of equine infectious anemia virus (EIAV), another lentivirus of the Retroviridae family. First, eADAR1 significantly promoted EIAV replication, and the enhancement of viral protein expression was associated with the long terminal repeat (LTR) and Rev response element (RRE) regions. Second, the RNA binding domain 1 of eADAR1 was essential only for enhancing LTR-mediated gene expression. Third, in contrast with APOBEC proteins, which have been shown to reduce lentiviral infectivity, eADAR1 increased the EIAV infectivity. This study indicated that eADAR1 was proviral rather than antiviral for EIAV., (Copyright © 2014 Elsevier Inc. All rights reserved.)

High rate food consumption in urban cities causes vast amounts of nitrogen and phosphorus used in agriculture to end up in urban wastewaters. To substantially recover these nutrients, source-separated human urine should be targeted. The present study was to investigate the feasibility of recovering nitrogen and phosphorus in urine via microalgae cultivation. In concentrated urine, urea hydrolysis and precipitation occur rapidly, making microalgal growth difficult and nutrient recovery ineffective. However, when fresh urine was added as nutrient stock for 1-day growth requirement, biomass of Chlorella sorokiniana grew from 0.44 to 0.96 g L(-1) utilising 62.64 mg L(-1) of N and 10.64 mg L(-1) of P, achieving 80.4% and 96.6% recoveries, respectively in a 1-day non-sterile cultivation cycle. Overall, microalgae grown with urine added as nutrient supplement show no signs of inferiority as compared to those grown in recipe medium BG11 in terms of mass and chlorophyll a growth rates as well as resulting lipids (36.8%) and energy contents (21.0 kJ g(-1))., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The commonest ways of diagnosing brucellosis in animals include the Rose-Bengal plate agglutination test, the buffered plate agglutination test (BPA), the slide agglutination test, the complement fixation test, and the indirect enzyme linked immunosorbent assay (I-ELISA). However, these methods cannot discriminate the Brucella vaccine strain (Brucella suis strain 2; B. suis S2) from naturally acquired virulent strains. Of the six common Brucella species, Brucella melitensis, Brucella abortus, and B. suis are the commonest species occurring in China. To develop an ELISA assay that can differentiate between cows inoculated with B. suis S2 and naturally infected with B. abortus and B. melitensis, genomic sequences from six Brucella spp. (B. melitensis, B. abortus, B. suis, Brucella canis, Brucella neotomae and Brucella ovis) were compared using Basic Local Alignment Search Tool software. One particular gene, the repA-related gene, was found to be a marker that can differentiate B. suis from B. abortus and B. melitensis. The repA-related gene of B. suis was PCR amplified and subcloned into the pET-32a vector. Expressed repA-related protein was purified and used as an antigen. The repA-based ELISA was optimized and used as specific tests. In the present study, serum from animals inoculated with the B. suis S2 vaccine strain had positive repA-based ELISA results. In contrast, the test-positive reference sera against B. abortus and B. melitensis had negative repA-based ELISA results. The concordance rate between B. abortus antibody-negative (based on the repA-based ELISA) and the Brucella gene-positive (based on the 'Bruce ladder' multiplex PCR) was 100%. Therefore, the findings suggest that the repA-based ELISA is a useful tool for differentiating cows vaccinated with the B. suis S2 and naturally infected with B. abortus and B. melitensis., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

To enhance local water security, the Singapore government promotes two water conservation policies: the use of eco-friendly toilets to reduce yellow water (YW) disposal and the installation of water efficient devices to minimize gray water (GW) discharge. The proposed water conservation policies have different impacts on the environmental performance of local wastewater management. The main purpose of this study is to examine and compare the impacts of different domestic wastewater streams and the effectiveness of two water conservation policies by means of life cycle assessment (LCA). LCA is used to compare three scenarios, including a baseline scenario (BL), YW-reduced scenario (YWR) and GW-reduced scenario (GWR). The BL is designed based on the current wastewater management system, whereas the latter two scenarios are constructed according to the two water conservation policies that are proposed by the Singapore government. The software SIMPARO 7.3 with local data and an eco-invent database is used to build up the model, and the functional unit is defined as the daily wastewater disposal of a Singapore resident. Due to local water supply characteristics, the system boundary is extended to include the sewage sludge management and tap water production processes. The characterization results indicate that the GWR has a significant impact reduction (22-25%) while the YWR has only a 2-4% impact reduction compared with the BL. The contribution analysis reveals that the GW dominates many impact categories except eutrophication potential. The tap water production is identified as the most influential process due to its high embodied energy demand in a local context. Life cycle costing analysis shows that both YWR and GWR are financially favorable. It is also revealed that the current water conservation policies could only achieve Singapore's short-term targets. Therefore, two additional strategies are recommended for achieving long-term goals. This study provides a comprehensive and reliable environmental profile of Singapore's wastewater management with the help of extended system boundary and local data. This work also fills the research gap of previous studies by identifying the contribution of different wastewater streams, which would serve as a good reference for source-separating sanitation system design., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Protein phosphatase type 2A (PP2A) can downregulate c-Jun N-terminal kinase (JNK) expression in monocytes stimulated by lipopolysaccharide. However, this effect has not been evaluated in patients with sepsis. We sought to determine whether PP2A/JNK pathway is involved in sepsis and whether PP2A expression can be associated with patient outcome., Materials and Methods: We measured PP2A, c-Jun, and JNK protein as well as PP2A and c-Jun messenger RNA in monocytes from trauma patients with (n = 24) or without (n = 22) sepsis 1 and 7 d after major trauma and from healthy volunteers (n = 15) by Western blotting and quantitative real-time polymerase chain reaction. Patient outcomes, including intensive care unit length of stay, Sequential Organ Failure Assessment score, and Multiple Organ Dysfunction score were compared between groups. Correlations between PP2A and c-Jun/JNK expression as well as patient outcomes were analyzed. Receiver operating characteristic analysis was performed to determine the diagnostic efficiency of PP2A for sepsis., Results: PP2A protein and messenger RNA expression were significantly higher in septic patients compared with nonseptic patients or healthy volunteers. Conversely, the expressions of JNK and c-Jun were significantly reduced in septic patients and correlated inversely with PP2A expression. Furthermore, PP2A expression was positively associated with LOS, Sequential Organ Failure Assessment and Multiple Organ Dysfunction score at day 1 and day 7. Receiver operating characteristic curve yielded a high sensitivity (87.5%) of PP2A in discriminating septic versus nonseptic patients., Conclusions: PP2A may serve as a negative regulator of the JNK pathway and a biomarker for sepsis., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Studies have reported divergent behavioral effects of depression on spontaneous vs. stimulus-evoked pain. However, the underlying neurobiological mechanisms are still unclear. The present study used a depression model of unpredictable chronic mild stress (UCMS) and pain models for spontaneous pain (i.e., the formalin test) and acute evoked pain (i.e., noxious thermal stimulation) in rats. The activity of neurons within thalamo-cortical circuits in the lateral and medial pain pathways was recorded by a multiple-channel recording technique, and behaviors were observed simultaneously. The results confirmed our previous findings that rats exposed to UCMS tended to exhibit decreased pain sensitivity to experimental stimuli but increased behavioral responses to ongoing pain. Based on the analysis of single-unit responses, the results demonstrated that the processing of spontaneous vs. evoked pain in a depressive-like state was altered in the opposite direction (activation vs. inhibition). The ensemble encoding analysis revealed that exposure to UCMS gave rise to enhanced inter-regional functional connectivity in spontaneous pain processing, but did not influence that of evoked pain. In addition, different brain activation patterns underlying the processing of spontaneous vs. evoked pain were observed. These findings revealed that the distinct response patterns of neurons within the pain-related brain circuits, especially in the affective pain pathway, mediate the divergent effects of depression on spontaneous vs. evoked pain. This is also the first report on the electrophysiology of depression models that provides direct evidence that the effect of depression on spontaneous and evoked pain may involve different brain mechanisms., (© 2013.)

Objective: To determine the impact of perceived-stress over one's own health, financial condition, job, and conflict with family members, and family members' problems on depressive symptoms in older adults., Methods: We analyzed datasets of the Taiwan Longitudinal Survey on Aging, and used self-reported stress in 2003 and 2007 to represent long-term stress conditions in 4854 ≥ 50-year old persons. The impact of long-term stress on depressive status (evaluated with CES-D10, score range 0-30) was determined with multivariate logistic regression analysis. Persons with proxy interviews, incomplete CES-D data, or cognitive impairment were excluded., Results: Perceived-health stress had stronger impacts on depressive symptoms than most other stress situations. Job-related stress showed no impact. Other stress situations showed modest associations in the middle-aged and young-olds. Ongoing stress had stronger impacts than past stress. Excluding health and job stresses, the impact generally decreased with aging. The association with clinically relevant depression generally followed that with depressive symptoms., Conclusion: All perceived stresses are not equal in their impacts on subsequent depressive symptoms. Perceived-health stress has stronger impacts under most conditions. Better understanding of the associations of various stressors with depressive symptoms could enhance planning of effective strategies to reduce the risk of depression in older persons., (© 2013.)

Multipotent mesenchymal stem cells (MSCs) have been isolated from several tumors and are implicated to play critical roles to increase malignant cell growth, invasion and metastasis. Here, we show that the MSC-like cells were isolated from human colon cancer tissues. These isolated hCC-MSCs (human colon cancer-derived mesenchymal stem cells) shared similar characteristic features with bone marrow-derived MSCs, which include cell morphology, surface antigens and specific gene expression. Additionally, the hCC-MSCs could differentiate into osteocytes or adipocytes under appropriate culture conditions. The conditioned medium collected from the cultured hCC-MSCs was shown to enhance the migration and invasive activity of HCT-116 colon cancer cells in vitro. Besides, transplantation of HCT-116 cells along with hCC-MSCs in nude mice increased the tumor growth and metastasis. Further study revealed that IL-6 present in the hCC-MSC-conditioned medium sufficiently induced the levels of Notch-1 and CD44 in HCT-116 and HT-29 cells, which contribute to enhance tumorigenic activity of HCT-116 and HT-29 cells. By using immunohistochemical staining, the intense co-expression of IL-6, Notch-1 and CD44 was predominantly detected in human colon cancer tissues. Taken together, our findings suggest the importance of the IL-6/Notch-1/CD44 signaling axis in the interaction between hCC-MSCs and colon cancer cells., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: The objective of this study is to determine the concurrent and longitudinal associations of lifestyle factors including smoking, alcohol drinking, betel quid chewing, tea (Camellia sinensis) drinking and physical activity with depressive symptoms in older Taiwanese., Methods: The study analyzed Taiwan Longitudinal Study on Aging (TLSA) datasets to determine the association of lifestyle variables with concurrent depressive symptoms in 4122 ≥ 50-year-old Taiwanese at baseline (1999) and with the new development of depressive symptoms 8 years later., Results: Heavy/problem alcohol drinking increased the association with concurrent depressive symptoms (OR=1.85, 95%CI=1.02-3.36); frequent tea drinking (OR=0.63, 95%CI=0.50-0.79) and frequent physical activity (OR=0.59, 95%CI=0.48-0.71) reduced the association; whereas smoking and betel quid chewing showed no significant associations. Smoking (OR=1.56, 95%CI=1.06-2.30) increased the development of depressive symptoms 8 years later; past smoking and current betel quid chewing showed similar trends (OR=1.47, 95%CI=0.93-2.31); exercising ≥ 3 times/wk reduced the development (OR=0.77, 95%CI=0.60-0.99) while alcohol drinking showed no impact., Conclusion: Lifestyle variables can impact the mental wellbeing of older Taiwanese. Interventions to reduce the risk of depressive symptoms in older adults should include strategies aimed at improving these modifiable risk factors., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Osteoporosis and colorectal cancer (CRC) in older women are considered enormous public health burdens. The effects of osteoporosis on the oncologic outcome of CRC surgery are poorly understood. We evaluated the use of the Osteoporosis Self-assessment Tool for Asians (OSTA) for predicting postoperative outcome in older women after receiving surgical treatment of CRC., Materials and Methods: The present single-institution retrospective study analyzed patients who had undergone surgery for CRC in 2002-2008. To characterize the major population of women with osteoporosis, which consists of postmenopausal women, only patients aged 50 years and older were analyzed. Their OSTA scores were evaluated for correlations with cancer-specific survival after surgery for CRC by performing univariate, multivariate, and survival analyses., Results: During a 7-year period, 440 women were studied. The cancer-specific mortality and overall mortality rate was 28.4% and 33.4%, respectively. The univariate analyses revealed that significant predictors of cancer-specific mortality after CRC surgery were the International Union Against Cancer (UICC) stage, OSTA category, histologic grading, lymph node metastases, and tumor invasion depth. After risk adjustment, the UICC stage and OSTA risk index were independent predictors of mortality. A comparison of OSTA risk index among patients with different UICC stages showed that the accuracy of the index in predicting cancer-specific survival after CRC surgery was greatest for patients with stage II and III disease., Conclusions: The UICC stage and OSTA risk status showed independent positive associations with postoperative mortality in aged female patients with CRC. Moreover, the OSTA index had a particularly strong association with cancer-specific mortality in patients with UICC stage II and III., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The fragile X mental retardation 1 (FMR1) gene plays an important role in the development and maintenance of neuronal circuits that are essential for cognitive functioning. We explored the functional linkage(s) among lymphocytic FMR1 gene expression, brain structure, and working memory in healthy adult males. We acquired T1-weighted and diffusion tensor imaging from 37 males (18-80 years, mean ± SD= 40.7 ± 17.3 years) with normal FMR1 alleles and performed genetic and working memory assessments. Brain measurements were obtained from fiber tracts important for working memory (i.e. the arcuate fasciculus, anterior cingulum bundle, inferior longitudinal fasciculus, and the genu and anterior body of the corpus callosum), individual voxels, and whole brain. Both FMR1 mRNA and protein (FMRP) levels exhibited significant associations with brain measurements, with FMRP correlating positively with gray matter volume and white matter structural organization, and FMR1 mRNA negatively with white matter structural organization. The correlation was widespread, impacting rostral white matter and 2 working-memory fiber tracts for FMRP, and all cerebral white matter areas except the fornix and cerebellar peduncles and all 4 fiber tracts for FMR1 mRNA. In addition, the levels of FMR1 mRNA as well as the fiber tracts demonstrated a significant correlation with working memory performance. While FMR1 mRNA exhibited a negative correlation with working memory, fiber tract structural organization showed a positive correlation. These findings suggest that the FMR1 gene is a genetic factor common for both working memory and brain structure, and has implications for our understanding of the transmission of intelligence and brain structure., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Methamphetamine (METH) is a drug of abuse which causes neurotoxicity and increased risk of developing neurodegenerative diseases. We previously found that METH induces heme oxygenase (HO)-1 expression in neurons and glial cells, and this offers partial protection against METH toxicity. In this study, we investigated the effects of l-ascorbate (vitamin C, Vit. C) on METH toxicity and HO-1 expression in neuronal/glial cocultures. Cell viability and damage were evaluated by 3-(4,5-dimethylthianol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT) reduction and lactate dehydrogenase (LDH) release, respectively. Neuronal and glial localization of HO-1 were identified by double immunofluorescence staining. Reactive oxygen species (ROS) production was measured using the fluorochrome 2',7'-dichlorofluorescin diacetate. HO-1 mRNA and protein expression were examined by RT-qPCR and Western blotting, respectively. Results show that Vit. C induced HO-1 mRNA and protein expressions in time- and concentration-dependent manners. Inhibition of p38 mitogen-activated protein kinase (MAPK) but not extracellular signal-regulated kinase (ERK) significantly blocked induction of HO-1 by Vit. C. HO-1 mRNA and protein expressions were significantly elevated by a combination of Vit. C and METH, compared to either Vit. C or METH alone. Pretreatment with Vit. C enhanced METH-induced HO-1 expression and attenuated METH-induced ROS production and neurotoxicity. Pharmacological inhibition of HO activity abolished suppressive effects of Vit. C on METH-induced ROS production and attenuated neurotoxicity. We conclude that induction of HO-1 expression contributes to the attenuation of METH-induced ROS production and neurotoxicity by Vit. C. We suggest that HO-1 induction by Vit. C may serve as a strategy to alleviate METH neurotoxicity., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Monodisperse microspheres composed of thermo-responsive poly(N-isopropylacrylamide) (PNIPAM) core and biocompatible porous ethyl cellulose (EC) shell embedded with PNIPAM gates have been successfully prepared by microfluidic emulsification, solvent evaporation and free radical polymerization. Attributing to the coating of EC shell, the mechanical strength and biocompatibility of the core-shell microsphere are much better than those of the PNIPAM core itself. Fourier transform infrared (FT-IR) spectrometer and scanning electron microscopy (SEM) are employed to examine chemical compositions and microstructures of prepared microparticles. By the cooperative action of EC shell with PNIPAM gates and PNIPAM core, the proposed core-shell microspheres exhibit satisfactory thermo-responsive controlled release behaviors of model drug molecules rhodamine B (Rd B) and VB12. At temperatures above the volume phase transition temperature (VPTT) of PNIPAM, the release rate of solute molecules is much faster than that at temperatures below the VPTT. The controlled factor of the prepared core-shell microspheres for VB12 release reaches to as high as 11.7. The proposed microspheres are highly attractive for controlled drug delivery., (Copyright © 2012 Elsevier Inc. All rights reserved.)

In this study, the adsorption of Cu(II) from aqueous solutions by agricultural by-products, such as rice husks, olive pomace and orange waste, as well as compost, was evaluated. The aim was to obtain sorbent materials (biochars) through hydrothermal treatment (300 °C) and pyrolysis (300 °C and 600 °C). The effect of adsorbent dose, pH, contact time and initial Cu(II) concentration in batch-mode experiments was investigated. The optimum Cu(II) adsorption conditions was found to occur at 5-12 g/L adsorbent dose, initial pH 5-6, and reaction time 2-4 h. Furthermore, the adsorption kinetics were best described by the pseudo-second order model for all the tested materials, while the adsorption equilibrium best fitted by the linear and Freundlich isotherms. Comparing rice husks and olive pomace, the higher adsorption capacity resulted after pyrolysis at 300 °C. With respect to the orange waste and compost, the highest adsorption capacity was observed using biochars obtained after hydrothermal treatment and pyrolysis at 300 °C., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Diffusion tensor tractography is increasingly used to examine structural connectivity in the brain in various conditions, but its test-retest reliability is understudied. The main purposes of this study were to evaluate 1) the reliability of quantitative measurements of diffusion tensor tractography and 2) the effect on reliability of the number of gradient sampling directions and scan repetition. Images were acquired from ten healthy participants. Ten fiber regions of nine major fiber tracts were reconstructed and quantified using six fiber variables. Intra- and inter-session reliabilities were estimated using intraclass correlation coefficient (ICC) and coefficient of variation (CV), and were compared to pinpoint major error sources. Additional pairwise comparisons were made between the reliability of images with 30 directions and NEX 2 (DTI30-2), 30 directions and NEX 1 (DTI30-1), and 15 directions and NEX 2 (DTI15-2) to determine whether increasing gradient directions and scan repetition improved reliability. Of the 60 tractography measurements, 43 showed intersession CV ≤ 10%, ICC ≥ .70, or both for DTI30-2, 40 measurements for DTI30-1, and 37 for DTI15-2. Most of the reliable measurements were associated with the tracts corpus callosum, cingulum, cerebral peduncular fibers, uncinate fasciculus, and arcuate fasciculus. These reliable measurements included factional anisotropy (FA) and mean diffusivity of all 10 fiber regions. Intersession reliability was significantly worse than intra-session reliability for FA, mean length, and tract volume measurements from DTI15-2, indicating that the combination of MRI signal variation and physiological noise/change over time was the major error source for this sequence. Increasing the number of gradient directions from 15 to 30 while controlling the scan time, significantly affected values for all six variables and reduced intersession variability for mean length and tract volume measurements. Additionally, while increasing scan repetition from 1 to 2 had no significant effect on the reliability for DTI with 30 directions, this significantly reduced the upward bias in FA values from all 10 fiber regions and fiber count, mean length, and tract volume measurements from 5 to 7 fiber regions. In conclusion, diffusion tensor tractography provided many measurements with high test-retest reliability across different fiber variables and various fiber tracts even for images with 15 directions (NEX 2). Increasing the number of gradient directions from 15 to 30 with equivalent scan time reduced variability whereas increasing repetition from 1 to 2 for 30-direction DTI improved the accuracy of tractography measurements., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Naphthoquine (NQ), as a component of ARCO® which composed of NQ and artemisinin, is a new 4-aminoquinoline antimalarial synthesized by our institute. Here, a naphthoquine-resistant line of rodent malaria parasite was selected through exposing Plasmodium berghei Keyberg 173 strain to progressively increased drug pressure. The selected strain showed a more than 200-fold decreased susceptibility to NQ with a stable resistance phenotype after 10 serial passages without drug pressure or when cryopreserved over a period of 12 months. In a cross-resistance assay, the susceptibility of NQ-resistant parasites to chloroquine was decreased by 14.5-fold. These findings imply NQ-resistant parasites might be selected by long-term usage of NQ in epidemic areas and the efficacy of NQ or ARCO® in chloroquine-resistant Plasmodium falciparum epidemic areas should be monitored closely., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Novel calcium-alginate (Ca-alginate) capsules with aqueous core and thermo-responsive membrane are successfully prepared by introducing a co-extrusion minifluidic approach, and the thermo-responsive gating characteristics of Ca-alginate capsule membranes embedded with poly(N-isopropylacrylamide) (PNIPAM) microspheres are investigated systematically. The experimental results show that the prepared Ca-alginate capsules are highly monodisperse, and the average diameter and membrane thickness of Ca-alginate capsules are about 2.96 mm and 0.11 mm respectively. The Ca-alginate capsule membranes exhibit desired thermo-responsive gating property. With increasing the content of PNIPAM microspheres embedded in the Ca-alginate capsule membranes, the thermo-responsive gating coefficient of the capsule membranes increases simply. When solute molecules diffuse through the capsule membrane, the thermo-responsive gating coefficient is significantly affected by the molecular weight of solute molecules., (Copyright © 2010 Elsevier Inc. All rights reserved.)