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Abstract Invasive nontyphoidal Salmonella (iNTS) causes extraintestinal infections with ~15% case fatality in many countries. However, the mechanism by which iNTS emerged in China remains unaddressed. We conducted clinical investigations of iNTS infection with recurrent treatment failure, caused by underreported Salmonella enterica serovar Livingstone (SL). Genomic epidemiology demonstrated five clades in the SL population and suggested that the international animal feed trade was a likely vehicle for their introduction into China, as evidenced by multiple independent transmission incidents. Importantly, isolates from Clade‐5‐I‐a/b, predominant in China, showed an invasive nature in mice, chicken and zebrafish infection models. The antimicrobial susceptibility testing revealed most isolates (> 96%) in China are multidrug‐resistant (MDR). Overall, we offer exploiting genomics in uncovering international transmission led by the animal feed trade and highlight an emerging hypervirulent clade with increased resistance to frontline antibiotics.

Tea plantations are expanding globally and many are in mountainous areas with frequent fog but few studies have examined fog chemistry in these areas. We examined chemical composition of fog and rain water at a tea plantation in northern Taiwan. Fog water was collected using a Kroneis passive cylindrical fog-water collector and rain water was collected using a 20-cm-diameter funnel. The most abundant ions were Cl− and Na+ in both fog and rain waters due to the proximity of the site to the coast. The order of abundance of other ions was NO3− > Mg2+ > SO42− > Ca2+ > NH4+ > K+ > H+ in fog water and SO42− > K+ > NO3− > NH4+ > Ca2+ > Mg2+ > H+ in rain water. The concentration enrichment ratio (fog to rain) ranged between 2.2 (K+) and 22 (Mg2+) lying between sites near major emission sources and sites in remote areas, possibly because the immediate surrounding landscape is covered with secondary forests although it is near large cities. Factor analysis highlights the influences of sea-salt aerosols on the variation of fog and rain water chemistry. Sea-salt corrections using Na+ as the sea salt tracer led to negative concentrations of Cl− and Mg2+ suggesting that assumptions involved in sea-salt corrections were not satisfied. Agriculture influence is identified as a unique factor for explaining variance of K+, NH4+, and dissolved organic nitrogen (DON) concentrations in fog water but not rain water. Ion concentrations in fog and rain water were generally higher in the weekly samples associated with air trajectories passing through the continental East Asia than those associated with oceanic trajectories pointing to the role of regional pollution sources in affecting local fog and rain water chemistry. Our study highlights greater effects of tea agriculture on fog than rain water chemistry. [ABSTRACT FROM AUTHOR]

Ergothioneine (ET) is a naturally occurring antioxidant and cytoprotective agent that is synthesized by fungi and certain bacteria. Recent studies have shown a beneficial effect of ET on neurological functions, including cognition and animal models of depression. The aim of this study is to elucidate a possible effect of ET in rodent models of stroke. Post-ischemic intracerebroventricular (i.c.v.) infusion of ET significantly reduced brain infarct volume by as early as 1 day after infusion in rats, as shown by triphenyltetrazolium chloride (TTC) assay. There was a dose-dependent increase in protection, from 50 to 200 ng of ET infusion. These results suggest that ET could have a protective effect on CNS neurons. We next elucidated the effect of systemic ET on brain infarct volume in mice after stroke. Daily i.p. injection of 35 mg/kg ET (the first dose being administered 3 h after stroke) had no significant effect on infarct volume. However, daily i.p. injections of 70 mg/kg, 100 mg/kg, 125 mg/kg and 150 mg/kg ET, with the first dose administered 3 h after stroke, significantly decreased infarct volume at 7 days after vessel occlusion in mice. In order to elucidate at what time interval during the 7 days there could be effective protection, a second set of experiments was carried out in mice, using one of the effective loading protocols, i.e. 125 mg/kg i.p. ET but the brains were analyzed at 1, 4 and 7 days post-stroke by MRI. We found that ET was already protective against neuronal injury and decreased the size of the brain infarct from as early as 1 day post-stroke. Behavioral experiments carried out on a third set of mice (using 125 mg/kg i.p. ET) showed that this was accompanied by significant improvements in certain behaviors (pole test) at 1 day after stroke. Together, results of this study indicate that i.c.v. and systemic ET are effective in reducing brain infarct volume after stroke in rodent models. [ABSTRACT FROM AUTHOR]

Neuroinflammation has been shown to exacerbate ischemic brain injury, and is considered as a prime target for the development of stroke therapies. Clinacanthus nutans Lindau (C. nutans) is widely used in traditional medicine for treating insect bites, viral infection and cancer, due largely to its anti-oxidative and anti-inflammatory properties. Recently, we reported that an ethanol extract from the leaf of C. nutans could protect the brain against ischemia-triggered neuronal death and infarction. In order to further understand the molecular mechanism(s) for its beneficial effects, two experimental paradigms, namely, in vitro primary cortical neurons subjected to oxygen–glucose deprivation (OGD) and in vivo rat middle cerebral artery (MCA) occlusion, were used to dissect the anti-inflammatory effects of C. nutans extract. Using promoter assays, immunofluorescence staining, and loss-of-function (siRNA) approaches, we demonstrated that transient OGD led to marked induction of IL-1β, IL-6 and TNFα, while pretreatment with C. nutans suppressed production of inflammatory cytokines in primary neurons. C. nutans inhibited IL-1β transcription via preventing NF-κB/p65 nuclear translocation, and siRNA knockdown of either p65 or IL-1β mitigated OGD-mediated neuronal death. Correspondingly, post-ischemic treatment of C. nutans attenuated IκBα degradation and decreased IL-1β, IL-6 and TNFα production in the ischemic brain. Furthermore, IL-1β siRNA post-ischemic treatment reduced cerebral infarct, thus mimicking the beneficial effects of C. nutans. In summary, our findings demonstrated the ability for C. nutans to suppress NF-κB nuclear translocation and inhibit IL-1β transcription in ischemic models. Results further suggest the possibility for using C. nutans to prevent and treat stroke patients. [ABSTRACT FROM AUTHOR]

Dissolved organic matter (DOM) plays a key role in soil organic matter (SOM) decomposition via the priming effect (PE). The DOM-induced soil PE is closely related to nutrient availability, especially nitrogen (N). Regardless of the widespread of chronic N addition, how elevated N deposition affects DOM-induced PEs remains poorly understood. To fill this knowledge gap, we studied the effects of N addition, 13C-labeled leaf-DOM (herein DOM) addition, and leaf-DOM plus N addition (DOM+N) on soil PEs in soils of a subtropical Chinese-fir (Cunninghamia lanceolata) plantation and a natural Castanopsis carlesii forest (hereafter referred to as Chinese-fir soil and Castanopsis soil, respectively). Soil properties (e.g., soil organic C, total N, available phosphorus, and ratio of C and N), dissolved organic C (DOC), soil microbial biomass C (MBC), phospholipid fatty acid (PLFA), and enzyme activities were also investigated, because these parameters predominantly affect the intensity and direction of soil priming. The addition of DOM induced positive PEs in the Castanopsis soil but negative PEs in the Chinese-fir soil. In addition, DOM addition increased MBC and fungal abundance and the activities of phenol oxidase (PhOx) and peroxidase (Perox) in the Castanopsis soil but not in the Chinese-fir soil. Compared with DOM-only addition, DOM+N addition significantly enhanced PEs in the Chinese-fir soil but not in the Castanopsis soil. Furthermore, compared with DOM-only addition, DOM+N addition significantly increased MBC, abundance of fungi and AMF, fungi to bacteria ratio (F:B), and activities of four enzymes [β-glucosidase (βG), N-acetyl glucosaminidase (NAG), PhOx, and Perox] in the Chinese-fir soil but not in the Castanopsis soil. The DOM+N addition also had a significant effect on composition of main microbial groups in the Chinese-fir soil but not in the Castanopsis soil. These results suggest the enhanced PE following DOM+N in the Chinese-fir soil was likely mediated by enhanced enzyme production associated with increased fungal abundance. Our study highlights that the effects of increases of DOM on soil C cycling is largely affected by N availability and mediated by the effects on the abundance of soil microbial groups and enzyme activities. Our result also demonstrated a case in which effects of DOM and N addition on soil C cycling differ between a Castanopsis forest and a Chinese-fir plantation forest, with Chinese-fir soil being more sensitive to N addition. This is an important finding that needs to be taken into consideration in estimating the soil C pools. [ABSTRACT FROM AUTHOR]

Aims: Changes in plant net primary production due to climate change can influence aboveground and belowground litter inputs to forest soils. We aim to examine the effects of such changes on soil carbon in subtropical forest ecosystems where these effects have not been thoroughly investigated. Methods: We manipulated aboveground litter inputs and excluded roots in a factorial design, and measured the effects of each treatment and their interactions on soil carbon (C) and soil microbial community structure. Results: After only 3 years of treatment, aboveground litter addition and root exclusion respectively caused 9% and 21% reductions in soil C concentration in the 0–10 cm soil, likely through different mechanisms. The reduction of soil C with aboveground litter addition was attributed to a priming effect, while reduced root-derived C inputs were likely the cause of the C reduction associated with root exclusion. PLFA analysis showed that both aboveground and belowground litter manipulations reduced Gram-positive bacteria biomass (by 30%–58%) compare to the control, but only root exclusion significantly reduced the actinobacteria biomarkers (by 46%–58%). Fungi, arbuscular mycorrhizal fungi, and ratios of Gram-negative to Gram-positive bacteria and bacteria to fungi did not differ among treatments. Conclusion: Our results show that root-derived C inputs exert a stronger control on soil C concentrations and microbial community structures than aboveground litter does in subtropical natural forest soils. Our study also highlights that that both increases in aboveground litter and decreases in belowground C input to soil can lead to reduced soil C. [ABSTRACT FROM AUTHOR]

Many properties of forest ecosystems, such as species composition and forest structure, naturally vary with forest age. However, in regions prone to cyclone disturbances, both forest age and cyclone severities can play a role shaping these properties. To evaluate potential effects of an altered cyclone regime on forest ecosystems, it is necessary to disentangle the roles of cyclones and forest age on different forest characteristics. In this study, we compared species composition and forest structure at plot level across sites with similar climate and topographic backgrounds, yet differing in age and typhoon severities in northeastern Taiwan. We found shorter tree stature, higher wood density, higher tree species diversity, and lower typhoon-induced tree mortality in the sites with more severe typhoon disturbances. On the other hand, regardless of typhoon severity, the sites of younger ages had a considerably smaller amount of woody debris, suggesting that it takes time for the accumulation of woody debris. More typhoon-induced canopy gaps at sites with more severe typhoon influences highlights a role of typhoons in canopy dynamics. However, the lack of gaps prior to typhoon disturbances in the less severely affected forest is likely related to the low background mortality associated with the relative young age of the forest. Our results indicate that frequent or severe typhoon disturbances can homogenize some of the structural differences among forests of different ages. If the frequency or severity of cyclones increase in the future, many forests, including old-growth forests, may gradually lose large trees. [ABSTRACT FROM AUTHOR]

Clinacanthus nutans Lindau (C. nutans) is a traditional herbal medicine widely used in Asian countries for treating a number of remedies including snake and insect bites, skin rashes, viral infections, and cancer. However, the underlying molecular mechanisms for its action and whether C. nutans can offer protection on stroke damage in brain remain largely unknown. In the present study, we demonstrated protective effects of C. nutans extract to ameliorate neuronal apoptotic death in the oxygen-glucose deprivation model and to reduce infarction and mitigate functional deficits in the middle cerebral artery occlusion model, either administered before or after hypoxic/ischemic insult. Using pharmacological antagonist and siRNA knockdown approaches, we demonstrated ability for C. nutans extract to protect neurons and ameliorate ischemic injury through promoting the anti-apoptotic activity of peroxisome proliferator-activated receptor-gamma (PPAR-γ), a stress-induced transcription factor. Reporter and chromatin immunoprecipitation promoter analysis further revealed C. nutans extract to selectively increase CCAAT/enhancer binding protein (C/EBP)β binding to specific C/EBP binding site (-332~-325) on the PPAR-γ promoter to augment its transcription. In summary, we report a novel transcriptional activation involving C/EBPβ upregulation of PPAR-γ expression to suppress ischemic neuronal apoptosis and brain infarct. Recognition of C. nutans to enhance the C/EBPβ → PPAR-γ neuroprotective signaling pathway paves a new way for future drug development for prevention and treatment of ischemic stroke and other neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

This paper investigates the association between board characteristics and the company’s corporate social responsibility (CSR) assurance decision in China. By examining 2054 firm-years of Chinese listed companies with CSR reports from 2008 to 2012, we find that firms with a large board size, more female directors, and separation of CEO and chairman positions are more likely to engage in CSR assurance. Gender diversity also influences the CSR assurance provider choice. However, board independence and overseas background of the CEO do not affect the CSR assurance decision. Inconsistent with our prediction, firms with foreign directors are less likely to engage in voluntary CSR assurance. In summary, this research provides in-depth insights into the determinants of Chinese firms’ voluntary CSR assurance. [ABSTRACT FROM AUTHOR]

The omega-3 polyunsaturated fatty acid, docosahexaenoic acid (DHA) is enriched in neural membranes of the CNS, and recent studies have shown a role of DHA metabolism by 15-lipoxygenase-1 (Alox15) in prefrontal cortex resolvin D1 formation, hippocampo-prefrontal cortical long-term-potentiation, spatial working memory, and anti-nociception/anxiety. In this study, we elucidated epigenetic regulation of Alox15 via histone modifications in neuron-like cells. Treatment of undifferentiated SH-SY5Y human neuroblastoma cells with the histone deacetylase (HDAC) inhibitors trichostatin A (TSA) and sodium butyrate significantly increased Alox15 mRNA expression. Moreover, Alox15 expression was markedly upregulated by Class I HDAC inhibitors, MS-275 and depsipeptide. Co-treatment of undifferentiated SH-SY5Y cells with the p300 histone acetyltransferase (HAT) inhibitor C646 and TSA or sodium butyrate showed that p300 HAT inhibition modulated TSA or sodium butyrate-induced Alox15 upregulation. Differentiation of SH-SY5Y cells with retinoic acid resulted in increased neurite outgrowth and Alox15 mRNA expression, while co-treatment with the p300 HAT inhibitor C646 and retinoic acid modulated the increases, indicating a role of p300 HAT in differentiation-associated Alox15 upregulation. Increasing Alox15 expression was found in primary murine cortical neurons during development from 3 to 10 days-in-vitro, reaching high levels of expression by 10 days-in-vitro—when Alox15 was not further upregulated by HDAC inhibition. Together, results indicate regulation of Alox15 mRNA expression in neuroblastoma cells by histone modifications, and increasing Alox15 expression in differentiating neurons. It is possible that one of the environmental influences on the immature brain that can affect cognition and memory, may take the form of epigenetic effects on Alox15 and metabolites of DHA. [ABSTRACT FROM AUTHOR]

Background and aims: Changes in net primary productivity in response to climate change are likely to affect litter inputs to forest soil. However, feedbacks between changes in litter input and soil carbon dynamics remain poorly understood in tropical and subtropical forests. This study aims to test whether the effects of litter manipulation on soil respiration differ between natural and plantation forests. Methods: Soil respiration, soil properties, fine root biomass and enzyme activity were measured in adjacent plots with doubling vs. eliminating litter input in both natural and plantation forests of Castanopsis carlesii in southern China. Results: After only 3 years of litter manipulation, the magnitude of change in soil respiration was greater in response to a doubling of the litter input (+24%) than to the elimination of litter input (−15%) in the natural forest, possibly due to a positive priming effect on decomposition of soil organic carbon (SOC). The quick and intense priming effect was corroborated by elevated enzyme activities for five of the six enzymes analyzed. In contrast, the response to litter removal (−31%) was greater than the response to litter addition (1%; not significant) in the plantation forest. The lack of positive priming in the plantation forest may be related to its lower soil fertility, which could not meet the demand of soil microbes, and to its high clay content, which protected SOC from microbial attack. The positive priming effect in the natural forest but not plantation forest of C. carlesii is also consistent with the significant declines in total soil carbon observed following litter addition in the natural forest but not the plantation forest. Conclusions: Increases in aboveground litter production may trigger priming effects and subsequently transfer more soil carbon to atmospheric CO in the natural forest but not in the plantation forest with low fertility. Changes in litter inputs resulting from global change drivers may have different impacts on natural and plantation forests. [ABSTRACT FROM AUTHOR]

Many population-based epidemiological studies have unveiled an inverse correlation between intake of herbal plants and incidence of stroke. C. nutans is a traditional herbal medicine widely used for snake bite, viral infection and cancer in Asian countries. However, its role in protecting stroke damage remains to be studied. Despite of growing evidence to support epigenetic regulation in the pathogenesis and recovery of stroke, a clear understanding of the underlying molecular mechanisms is still lacking. In the present study, primary cortical neurons were subjected to in vitro oxygen-glucose deprivation (OGD)-reoxygenation and hypoxic neuronal death was used to investigate the interaction between C. nutans and histone deacetylases (HDACs). Using pharmacological agents (HDAC inhibitor/activator), loss-of-function (HDAC siRNA) and gain-of-function (HDAC plasmid) approaches, we demonstrated an early induction of HDAC1/2/3/8 and HDAC6 in neurons after OGD insult. C. nutans extract selectively inhibited HDAC1 and HDAC6 expression and attenuated neuronal death. Results of reporter analysis further revealed that C. nutans suppressed HDAC1 and HDAC6 transcription. Besides ameliorating neuronal death, C. nutans also protected astrocytes and endothelial cells from hypoxic-induced cell death. In summary, results support ability for C. nutans to suppress post-hypoxic HDACs activation and mitigate against OGD-induced neuronal death. This study further opens a new avenue for the use of herbal medicines to regulate epigenetic control of brain injury. [ABSTRACT FROM AUTHOR]

Clinacanthus nutans Lindau ( C. nutans), commonly known as Sabah Snake Grass in southeast Asia, is widely used in folk medicine due to its analgesic, antiviral, and anti-inflammatory properties. Our recent study provided evidence for the regulation of cytosolic phospholipase A (cPLA) mRNA expression by epigenetic factors (Tan et al. in Mol Neurobiol. doi:, 2015). This enzyme catalyzes the release of arachidonic acid from glycerophospholipids, and formation of pro-inflammatory eicosanoids or toxic lipid peroxidation products such as 4-hydroxynonenal. In this study, we examined the effects of C. nutans ethanol leaf extracts on epigenetic regulation of cPLA mRNA expression in SH-SY5Y human neuroblastoma cells and mouse primary cortical neurons. C. nutans modulated induction of cPLA2 expression in SH-SY5Y cells by histone deacetylase (HDAC) inhibitors, MS-275, MC-1568, and TSA. C. nutans extracts also inhibited histone acetylase (HAT) activity. Levels of cPLA mRNA expression were increased in primary cortical neurons subjected to 0.5-h oxygen-glucose deprivation injury (OGD). This increase was significantly inhibited by C. nutans treatment. Treatment of primary neurons with the HDAC inhibitor MS-275 augmented OGD-induced cPLA mRNA expression, and this increase was modulated by C. nutans extracts. OGD-stimulated increase in cPLA mRNA expression was also reduced by a Tip60 HAT inhibitor, NU9056. In view of a key role of cPLA in the production of pro-inflammatory eicosanoids and free radical damage, and the fact that epigenetic effects on genes are often long-lasting, results suggest a role for C. nutans and phytochemicals to inhibit the production of arachidonic acid-derived pro-inflammatory eicosanoids and chronic inflammation, through epigenetic regulation of cPLA expression. [ABSTRACT FROM AUTHOR]

Peroxisome proliferator-activated receptor-gamma (PPAR-γ), a stress-induced transcription factor, protects neurons against ischemic stroke insult by reducing oxidative stress. NADPH oxidase (NOX) activation, a major driving force in ROS generation in the setting of reoxygenation/reperfusion, constitutes an important pathogenetic mechanism of ischemic brain damage. In the present study, both transient in vitro oxygen-glucose deprivation and in vivo middle cerebral artery (MCA) occlusion-reperfusion experimental paradigms of ischemic neuronal death were used to investigate the interaction between PPAR-γ and NOX. With pharmacological (PPAR-γ antagonist GW9662), loss-of-function (PPAR-γ siRNA), and gain-of-function (Ad-PPAR-γ) approaches, we first demonstrated that 15-deoxy-∆-PGJ (15d-PGJ), via selectively attenuating p22phox expression, inhibited NOX activation and the subsequent ROS generation and neuronal death in a PPAR-γ-dependent manner. Secondly, results of promoter analyses and subcellular localization studies further revealed that PPAR-γ, via inhibiting hypoxia-induced NF-κB nuclear translocation, indirectly suppressed NF-κB-driven p22phox transcription. Noteworthily, postischemic p22phox siRNA treatment not only reduced infarct volumes but also improved functional outcome. In summary, we report a novel transrepression mechanism involving PPAR-γ downregulation of p22phox expression to suppress the subsequent NOX activation, ischemic neuronal death, and brain infarct. Identification of a PPAR-γ → NF-κB → p22phox neuroprotective signaling cascade opens a new avenue for protecting the brain against ischemic insult. [ABSTRACT FROM AUTHOR]

Understanding factors controlling ecosystem structure and function is key to predicting the effects of climate change on vegetation distribution and carbon sequestration. Cyclones play a large role in structuring ecosystems and cyclone intensity is expected to increase on a warming planet. The effects of cyclones on broad-scale ecosystem patterns could be substantial but are poorly understood. This study assessed forest structure and biodiversity patterns across an elevation gradient (300-3000 m) in mountainous, humid forests of Taiwan, an island experiencing an average of 3-6 typhoons (regional name of cyclones) annually, and contrasted those patterns with a gradient within the Wuyi Mountains of China (500-2100 m), where the climate is similar to Taiwan but typhoon occurrence is rare and effects are generally minimal. In both Taiwan and the Wuyi Mountains, tree species richness and diversity decreased with increasing elevation. Tree size and stature decrease from low to high elevations in the typhoon-protected Wuyi Mountains. In contrast, the biomass and stature of forests in Taiwan increased from low to high elevations. The relationship between forest stature and climate was also contrasting in relation to typhoon disturbance in that we found decreasing tree height and basal area with increasing temperature in Taiwan, but not in the Wuyi Mountains. The more than twofold increase in tree height and biomass with increasing elevations reported here for subtropical humid forests of Taiwan is a unique pattern that highlights the potential role of cyclones in driving elevational patterns of forest structure. Climate change-induced alterations in tropical cyclone regimes may affect elevational patterns of forest structure and carbon sequestration in regions experiencing frequent cyclones. [ABSTRACT FROM AUTHOR]

Activating transcription factor 3 (ATF3) is a stress-induced transcription factor with diverse functions under disease states in multiple cell types. ATF3 has neuroprotective action against cerebral ischemia, which may involve caspase 3. However, the molecular mechanisms underlying ATF3 regulation of apoptosis are largely unknown. Here, we used gain- and loss-of-function and rescue approaches to demonstrate ATF3 attenuating hypoxic neuronal apoptosis. As well, the protective effect of ATF3 was mediated by downregulation of carboxyl-terminal modulator protein (CTMP), a pro-apoptotic factor that inhibits the anti-apoptotic Akt/PKB cascade. ATF3 (1) downregulated the mRNA and protein levels of CTMP; (2) its temporal expression pattern was reciprocal to that of CTMP; and (3) nuclear localization suggested that ATF3 may regulate CTMP transcription following hypoxic insult. Reporter assays demonstrated that ATF3 suppressed CTMP transcription, whereas ATF3 fusion with VP16, converting ATF3 to transcriptional activator, boosted CTMP transcription. By contrast, NF-κB increased CTMP transcription, and degradation-resistant IκBα decreased CTMP transcription. ChIP assays further confirmed that binding of ATF3 to the ATF/CREB site hindered NF-κB binding to the CTMP promoter, which repressed CTMP expression. Furthermore, CTMP siRNA treatment reduced hypoxic neuronal apoptosis by increasing p-Akt (Ser473) levels and leaving the upstream ATF3 level unchanged. We have identified an endogenous neuroprotective ATF3→CTMP signal cascade that may be a therapeutic target for reducing ischemic brain injury. [ABSTRACT FROM AUTHOR]

This paper extends research on the corporate governance practices of transitional economies by examining whether the ability of the audit committee to constrain earnings management in Chinese firms is associated with the listing environment and the presence of government officials on the audit committee. Despite considerable regulatory reforms by the Chinese Securities Regulatory Commission, there remain incentives for Chinese firms to manage earnings. However, government initiatives to encourage domestic firms to cross-list on the Hong Kong Stock Exchange are accompanied by improved governance. We find that the expertise and independence of the audit committee for cross-listed (CL) Chinese firms are associated with lower abnormal accruals, our measure of earnings management. Both domestic only listed firms and CL Chinese firms appoint government officials as independent members on the audit committee. However, due to the political connection between government officials and the controlling shareholder (the State), these appointments can severely mitigate audit committee independence. Subsequently, we find a significant and positive association between audit committee independence and experience and earnings management when there are government officials on the audit committee. [ABSTRACT FROM AUTHOR]

A new environment-friendly free-cutting steel alloyed with elemental Sn (Y20Sn) was developed to meet the requirements of machinability and mechanical properties according to GB/T8731-1988. The machinability of the steel is enhanced by the segregation of elemental Sn at grain boundaries. The effect of Sn segregation on intergranular brittle fracture at normal cutting temperature from 250°C to 400°C is confirmed. The formation mechanism of main inclusions MnS is influenced by the presence of Sn and the attachment of Sn around MnS itself as a surfactant, and this mechanism also explains the improvement in machinability and mechanical properties of the steel. In the steel, the relevant inclusions are mainly spherical or axiolitic, and are uniformly distributed in small volume. Such inclusions improve the machinability of the steel and do not impair the mechanical properties as well. Experimental results demonstrate that the appropriate content of Sn in the steel is 0.03wt% to 0.08wt%, and the remaining composition is close to that of standard Y20 steel. [ABSTRACT FROM AUTHOR]

15-Deoxy-∆-PGJ (15d-PGJ) and thiazolidinedione attenuate reactive oxygen species (ROS) production via a peroxisome proliferator-activated receptor-gamma (PPAR-γ)-dependent pathway. Nonetheless, how PPAR-γ mediates ROS production to ameliorate ischemic brain injury is not clear. Recent studies indicated that nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is the major source of ROS in the vascular system. In the present study, we used an in vitro oxygen-glucose deprivation and reoxygenation (hypoxia reoxygenation [HR]) paradigm to study whether PPAR-γ interacts with NADPH oxidase, thereby regulating ROS formation in cerebral endothelial cells (CECs). With pharmacological (PPAR-γ antagonist GW9662), loss-of-function (PPAR-γ siRNA), and gain-of-function (Ad-PPAR-γ) approaches, we first demonstrated that 15d-PGJ protected HR-treated CECs against ROS-induced apoptosis in a PPAR-γ-dependent manner. Results of promoter and subcellular localization analyses further revealed that 15d-PGJ, by activating PPAR-γ, blocked HR-induced NF-κB nuclear translocation, which led to inhibited transcription of the NADPH oxidase subunit p22phox. In summary, we report a novel transrepression mechanism whereby PPAR-γ downregulates hypoxia-activated p22phox transcription and the subsequent NADPH oxidase activation, ROS formation, and CEC apoptosis. [ABSTRACT FROM AUTHOR]

Trailing edge populations of upward migrating species induced by postglacial climatic warming can be evolutionarily significant in the face of global warming. We tested for population size changes between lower- and higher-elevation populations located in the same mountainous regions of the upward-shifting temperate woody species of the Rhododendron pseudochrysanthum complex in Taiwan. We also tested whether natural selection evoked adaptive divergence in trailing edge populations of this species complex. We genotyped 26 expressed sequence tag-simple sequence repeat (EST-SSR) loci of 185 individuals from nine populations of the R. pseudochrysanthum complex including Rhododendron rubropunctatum, Rhododendron hyperythrum, Rhododendron morii, and R. pseudochrysanthum. R. rubropunctatum populations in the R. pseudochrysanthum complex possessed the lowest estimates of genetic diversity and effective population size. Higher-elevation R. pseudochrysanthum populations had lower effective population sizes than lower-elevation R. morii populations in Hohuanshan and Tahsueshan, as revealed by estimates using both MIGRATE-N and approximate Bayesian computation (ABC). R. rubropunctatum populations diverged significantly from populations of other members of the R. pseudochrysanthum complex. An outlier potentially under positive selection specific to R. rubropunctatum populations was identified and strongly associated with ecologically relevant environmental variables. Postglacial climatic warming has a significant influence on population isolation in the R. pseudochrysanthum complex. The results indicate adaptive evolution in the trailing edge populations, i.e., R. rubropunctatum populations of the upward shifting R. pseudochrysanthum complex. [ABSTRACT FROM AUTHOR]

Alchemical free energy calculations hold increasing promise as an aid to drug discovery efforts. However, applications of these techniques in discovery projects have been relatively few, partly because of the difficulty of planning and setting up calculations. Here, we introduce lead optimization mapper, LOMAP, an automated algorithm to plan efficient relative free energy calculations between potential ligands within a substantial library of perhaps hundreds of compounds. In this approach, ligands are first grouped by structural similarity primarily based on the size of a (loosely defined) maximal common substructure, and then calculations are planned within and between sets of structurally related compounds. An emphasis is placed on ensuring that relative free energies can be obtained between any pair of compounds without combining the results of too many different relative free energy calculations (to avoid accumulation of error) and by providing some redundancy to allow for the possibility of error and consistency checking and provide some insight into when results can be expected to be unreliable. The algorithm is discussed in detail and a Python implementation, based on both Schrödinger's and OpenEye's APIs, has been made available freely under the BSD license. [ABSTRACT FROM AUTHOR]

As the growth of the aging population continues to accelerate globally, increased prevalence of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and stroke, has generated substantial public concern. Unfortunately, despite of discoveries of common factors underlying these diseases, few drugs are available to effectively treat these diseases. Peroxisome proliferator-activated receptor gamma (PPAR-γ) is a ligand-activated transcriptional factor that belongs to the nuclear hormone receptor superfamily. PPAR-γ has been shown to influence the expression or activity of a large number of genes in a variety of signaling networks, including regulation of insulin sensitivity, glucose homeostasis, fatty acid oxidation, immune responses, redox balance, cardiovascular integrity, and cell fates. Recent epidemiological, preclinical animal, and clinical studies also show that PPAR-γ agonists can lower the incidence of a number of neurological disorders, despite of multiple etiological factors involved in the development of these disorders. In this manuscript, we review current knowledge on mechanisms underlying the beneficial effect of PPAR-γ in different neurodegenerative diseases, in particular, AD, PD, and stroke, and attempt to analyze common and overlapping features among these diseases. Our investigation unveiled information suggesting the ability for PPAR-γ to inhibit NF-κB-mediated inflammatory signaling at multiple sites, and conclude that PPAR-γ agonists represent a novel class of drugs for treating neuroinflammatory diseases. [ABSTRACT FROM AUTHOR]

unique polymer-based sustained-release implant drug delivery system was prepared by using biocompatible and biodegradable Zein as the skeleton meterial. After preparing Zein colloids, the Zein-loaded implant rods were formulated by injection molding followed by evaporating the solvent, and being coated with poly(lactic- co-glycolic) acid (PLGA) solution. Drug release kinetics was examined by using Fluorouracil (5-FU) as model drug. Nearly zero-order release was achieved for the model drugs for a period of 0-25 days when the implants were incubated in distilled water at 37°C. And then the degradation kinetics of the rods in vivo and in vitro were evaluated, which indicated that Zein could be absorbed by body and has good degradation property. The effects of different ratios of Zein/5-FU and the rods' diameter on drug release were studied, respectively. The plasma concentration of 5-FU in the implants were determined by HPLC after implanting a single dose of the implants in rats. All data were subsequently processed by using the computer program 3P97, and the values were showed as follows: the area under the plasma concentration-time curve (AUC) value was 321.88 (μg/ml) × day, and the mean residence time (MRT) value was 23.05 days. The sustained-release implants of Zein/5-FU were successfully formulated. The uniqueness of the article is that Zein has been used as a skeleton material in implant delivery system for the first time and zero-order release kinetics has been obtained successfully. [ABSTRACT FROM AUTHOR]

Stroke is a leading cause of adult disability and mortality. Diabetes is a major risk factor for stroke. Patients with diabetes have a higher incidence of stroke and a poorer prognosis after stroke. Peroxisome proliferator-activated receptor gamma (PPAR-γ) is a ligand-modulated transcriptional factor and a therapeutic target for treating type II diabetes. It is well-documented that activation of PPAR-γ can also attenuate postischemic inflammation and damage. In this review, we focus on the newly revealed anti-apoptotic actions of PPAR-γ against cerebral ischemia. PPAR-γ, by increasing superoxide dismutase/catalase and decreasing nicotinamide adenine dinucleotide phosphate oxidase levels, attenuated ischemia-induced reactive oxygen species and subsequently alleviated the postischemic degradation of Bcl-2, Bcl-xl, and Akt. The preserved Akt phosphorylated Bad. Meanwhile, PPAR-γ also promotes the transcription of 14-3-3ε. Elevated 14-3-3ε binds and sequesters p-Bad and prevents Bad translocation to neutralize the anti-apoptotic function of Bcl-2. This review further supports the notion that PPAR-γ may serve as a potential therapeutic target for treating ischemic stroke. [ABSTRACT FROM AUTHOR]

Dysregulation of β-site APP-cleaving enzyme (BACE) and/or γ-secretase leads to anomalous production of amyloid-β peptide (Aβ) and contributes to the etiology of Alzheimer's disease (AD). Since these secretases mediate proteolytic processing of numerous proteins, little success has been achieved to treat AD by secretase inhibitors because of inevitable undesired side effects. Thus, it is of importance to unravel the regulatory mechanisms of these secretases. Here, we show that δ-opioid receptor (DOR) promotes the processing of Aβ precursor protein (APP) by BACE1 and γ-secretase, but not that of Notch, N-cadherin or APLP. Further investigation reveals that DOR forms a complex with BACE1 and γ-secretase, and activation of DOR mediates the co-endocytic sorting of the secretases/receptor complex for APP endoproteolysis. Dysfunction of the receptor retards the endocytosis of BACE1 and γ-secretase and thus the production of Aβ. Consistently, knockdown or antagonization of DOR reduces secretase activities and ameliorates Aβ pathology and Aβ-dependent behavioral deficits, but does not affect the processing of Notch, N-cadherin or APLP in AD model mice. Our study not only uncovers a molecular mechanism for the formation of a DOR/secretase complex that regulates the specificity of secretase for Aβ production but also suggests that intervention of either formation or trafficking of the GPCR/secretase complex could lead to a new strategy against AD, potentially with fewer side effects. [ABSTRACT FROM AUTHOR]

The original version of this article, unfortunately, contained an error. In Figure 2 - panel d, incorrect image was published and this is now presented correctly in this article. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor receptor–associated factor 6 (TRAF6) is critical for mediating Toll-like receptor (TLR)–interleukin 1 receptor (IL-1R) signaling and subsequent activation of NF-κB and AP-1, transcriptional activators of innate immunity. Here we show that β-arrestins, a family of multifunctional proteins, directly interacted with TRAF6 after TLR–IL-1R activation. Formation of the β-arrestin–TRAF6 complex prevented autoubiquitination of TRAF6 and activation of NF-κB and AP-1. Endotoxin-treated β-arrestin 2–deficient mice had higher expression of proinflammatory cytokines and were more susceptible to endotoxic shock. Thus, β-arrestins are essential negative regulators of innate immune activation via TLR–IL-1R signaling. [ABSTRACT FROM AUTHOR]

Takayasu’s arteritis (TA) is a vasculitis characterized by inflammation and obliteration of intermediate to large-size arteries. We report a case of Takayasu’s arteritis with a presentation of bilateral pulmonary nodular infiltrates in a 21-year-old man. An open-lung biopsy showed characteristic changes of extra-vascular granulomatosis. To our knowledge, this has not been described previously in the literature. [ABSTRACT FROM AUTHOR]

Aims: Soil mosses play an important role in carbon sequestration. We aimed to provide accurate estimates of CO2 flux and identify the drivers in subtropical moss-dominated biocrusts at diurnal and seasonal scales in subtropical China.We used an automated, continuous carbon flux measurement system with transparent chambers to measure net ecosystem exchange of CO2 (NEE) of the miniature ecosystem of moss-dominated biocrusts from April 2017 to March 2018.NEE during the study period ranged from -1.65 μmol m−2 s−1 to 1.77 μmol m−2 s−1, with a cumulative NEE of 95.14 g C m−2 y−1. On a daily basis, moss-dominated biocrusts acted as a carbon sink at daytime in the spring and winter but they acted as a carbon source at night-time throughout the year. Negative NEE (i.e., net carbon gain) was observed on 9% of the measurement days over the year, mostly when soil moisture was high. In the summer and autumn, moss-dominated biocrusts mostly acted as a carbon source throughout the entire day. Photosynthetically active radiation and soil moisture were the most important predictors of NEE variation. Daily NEE positively related to soil temperature, while soil moisture had a negative relationship with daytime NEE but not nighttime NEE.The strong temporal variation of NEE at the daily scale across different seasons emphasizes the importance of continuous flux measurements. This study also underscores the crucial role of soil moisture in affecting the carbon sink function of moss-dominated biocrusts in subtropical areas.Methods: Soil mosses play an important role in carbon sequestration. We aimed to provide accurate estimates of CO2 flux and identify the drivers in subtropical moss-dominated biocrusts at diurnal and seasonal scales in subtropical China.We used an automated, continuous carbon flux measurement system with transparent chambers to measure net ecosystem exchange of CO2 (NEE) of the miniature ecosystem of moss-dominated biocrusts from April 2017 to March 2018.NEE during the study period ranged from -1.65 μmol m−2 s−1 to 1.77 μmol m−2 s−1, with a cumulative NEE of 95.14 g C m−2 y−1. On a daily basis, moss-dominated biocrusts acted as a carbon sink at daytime in the spring and winter but they acted as a carbon source at night-time throughout the year. Negative NEE (i.e., net carbon gain) was observed on 9% of the measurement days over the year, mostly when soil moisture was high. In the summer and autumn, moss-dominated biocrusts mostly acted as a carbon source throughout the entire day. Photosynthetically active radiation and soil moisture were the most important predictors of NEE variation. Daily NEE positively related to soil temperature, while soil moisture had a negative relationship with daytime NEE but not nighttime NEE.The strong temporal variation of NEE at the daily scale across different seasons emphasizes the importance of continuous flux measurements. This study also underscores the crucial role of soil moisture in affecting the carbon sink function of moss-dominated biocrusts in subtropical areas.Results: Soil mosses play an important role in carbon sequestration. We aimed to provide accurate estimates of CO2 flux and identify the drivers in subtropical moss-dominated biocrusts at diurnal and seasonal scales in subtropical China.We used an automated, continuous carbon flux measurement system with transparent chambers to measure net ecosystem exchange of CO2 (NEE) of the miniature ecosystem of moss-dominated biocrusts from April 2017 to March 2018.NEE during the study period ranged from -1.65 μmol m−2 s−1 to 1.77 μmol m−2 s−1, with a cumulative NEE of 95.14 g C m−2 y−1. On a daily basis, moss-dominated biocrusts acted as a carbon sink at daytime in the spring and winter but they acted as a carbon source at night-time throughout the year. Negative NEE (i.e., net carbon gain) was observed on 9% of the measurement days over the year, mostly when soil moisture was high. In the summer and autumn, moss-dominated biocrusts mostly acted as a carbon source throughout the entire day. Photosynthetically active radiation and soil moisture were the most important predictors of NEE variation. Daily NEE positively related to soil temperature, while soil moisture had a negative relationship with daytime NEE but not nighttime NEE.The strong temporal variation of NEE at the daily scale across different seasons emphasizes the importance of continuous flux measurements. This study also underscores the crucial role of soil moisture in affecting the carbon sink function of moss-dominated biocrusts in subtropical areas.Conclusion: Soil mosses play an important role in carbon sequestration. We aimed to provide accurate estimates of CO2 flux and identify the drivers in subtropical moss-dominated biocrusts at diurnal and seasonal scales in subtropical China.We used an automated, continuous carbon flux measurement system with transparent chambers to measure net ecosystem exchange of CO2 (NEE) of the miniature ecosystem of moss-dominated biocrusts from April 2017 to March 2018.NEE during the study period ranged from -1.65 μmol m−2 s−1 to 1.77 μmol m−2 s−1, with a cumulative NEE of 95.14 g C m−2 y−1. On a daily basis, moss-dominated biocrusts acted as a carbon sink at daytime in the spring and winter but they acted as a carbon source at night-time throughout the year. Negative NEE (i.e., net carbon gain) was observed on 9% of the measurement days over the year, mostly when soil moisture was high. In the summer and autumn, moss-dominated biocrusts mostly acted as a carbon source throughout the entire day. Photosynthetically active radiation and soil moisture were the most important predictors of NEE variation. Daily NEE positively related to soil temperature, while soil moisture had a negative relationship with daytime NEE but not nighttime NEE.The strong temporal variation of NEE at the daily scale across different seasons emphasizes the importance of continuous flux measurements. This study also underscores the crucial role of soil moisture in affecting the carbon sink function of moss-dominated biocrusts in subtropical areas. [ABSTRACT FROM AUTHOR]

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper. [ABSTRACT FROM AUTHOR]

The Snail transcription factor plays as a master regulator of epithelial mesenchymal transition (EMT), one of the steps of tumor metastasis. Snail enhances expressions of a lot of mesenchymal genes including the matrix degradation enzyme matrix metalloproteinases 9 (MMP9) and the EMT transcription factor zinc finger E-box binding homeobox 1 (ZEB1), however, the underlying mechanisms are not clarified. Herein, we investigated how Snail upregulated transcription of ZEB1 and MMP9 induced by the tumor promoter 12-O-tetradecanoyl-phorbol 13-acetate (TPA) in hepatoma cell HepG2. According to deletion mapping and site directed mutagenesis analysis, the TPA-responsive elements on both MMP9 and ZEB1 promoters locate on a putative EGR1 and SP1 overlapping region coupled with an upstream proposed Snail binding motif TCACA. Consistently, chromatin immunoprecipitation (ChIP) assay showed TPA triggered binding of Snail, EGR1 and SP1 on MMP9 and ZEB1 promoters. Double ChIP further indicated TPA induced association of Snail with EGR1 and SP1 on both promoters. Also, electrophoresis mobility shift assay revealed TPA enhanced binding of Snail with a MMP9 promoter fragment. According to shRNA techniques, Snail was essential for gene expression of both ZEB1 and MMP9. In conclusion, Snail transactivates genes involved in tumor progression via direct binding to a specific promoter region. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article which discusses the administration of rituximab to treat immune thrombocytopenic pupura-induced reversible posterior leukoencephalopathy.

A letter to the editor is presented reporting on Hepatitis B virus (HBV) reactivation in patients induced by Rituximab maintenance therapy for lymphoma.

A letter to the editor is presented commenting on the significance of autologous peripheral blood stem cell transplantation in the case report of 33-year-old man suffering from monoclonal gammopathy and pyoderma gangrenosum, published in the previous issue of the journal.