Long-term relatively high dietary manganese intake could decrease the risk of hyperuricemia: Twelve-year distinct dietary manganese consumption trajectories and the China Health and Nutrition Survey.

BACKGROUND AND AIM: Currently, the relationship between dynamic changes in dietary manganese (Mn) intake and risk of hyperuricemia (HU) is still unclear. This study aimed to identify dietary Mn consumption trajectories in the Chinese adults and assess their relation with the risk of HU. METHODS AND RESULTS: Cohort data from the China Health and Nutrition Survey (CHNS) 1997-2009 were employed in this study. Overall, 6886 adult participants were included. Participants were designated into subgroups based on the trajectories of dietary Mn consumption by sex. Cox proportional hazard models were used to explore the associations between different trajectories and the risk of HU. For men, compared with low stable trajectory group, moderate to high trajectory group was significantly related to reduced risk of HU (HR = 0.61, 95% CI: 0.38 to 0.98) with adjustment for covariates. TC, HDL-C, ApoB, and TG exerted partial regulation function between trajectories and HU. For women, compared with low stable trajectory group, high stable trajectory group was significantly related to reduced risk of HU (HR = 0.76, 95% CI: 0.60 to 0.95) with adjustment for covariates. Similarly, TC, HDL-C, ApoB, and ApoA exerted partial regulation function between trajectories and HU. CONCLUSIONS: Long-term relatively high dietary Mn consumption may have a protective effect against HU in Chinese adults. The differences in HU-related factors among different dietary Mn intake trajectories partially regulated the association between these trajectories and HU.

Cutoff values of axial length/corneal radius ratio for determining myopia vary with age among 3-18 years old children and adolescents.

PURPOSE: To investigate the effectiveness and cutoffs of axial length/corneal radius (AL/CR) ratio for myopia detection in children by age. METHODS: Totally, 21 kindergartens and schools were enrolled. Non-cycloplegic autorefraction (NCAR), axial length (AL), horizontal and vertical meridian of corneal radius (CR1, CR2), and cycloplegic autorefraction were measured. Receiver operating characteristic (ROC) curve was used to obtain the effectiveness and cutoff for myopia detection. RESULTS: Finally, 7803 participants aged 3-18 years with mean AL/CR ratio of 2.99 ± 0.16 were included. Area under the ROC curve (AUC) of AL/CR ratio for myopia detection (0.958 for AL/CR1, 0.956 for AL/CR2, 0.961 for AL/CR) was significantly larger than that of AL (0.919, all P < 0.001), while AUCs of the three were similar with different cutoffs (> 2.98, > 3.05, and > 3.02). When divided by age, the ROC curves of AL/CR ratio in 3- to 5-year-olds showed no significance or low accuracy (AUCs ≤ 0.823) in both genders. In ≥ 6-year-olds, the accuracies were promising (AUCs ≥ 0.883, all P < 0.001), the cutoffs basically increased with age (from > 2.93 in 6-year-olds to > 3.07 in 18-year-olds among girls, and from > 2.96 in 6-year-olds to > 3.07 in 18-year-olds among boys). In addition, boys presented slightly larger cutoffs than girls in all ages except for 16 and 18 years old. For children aged 3-5 years, AL/CR ratio or AL combined with NCAR increased AUC to > 0.900. CONCLUSION: AL/CR ratio provided the best prediction of myopia with age-dependent cutoff values for all but preschool children, and the cutoffs of boys were slightly larger than those of girls. For preschool children, AL/CR ratio or AL combined with NCAR is recommended to achieve satisfactory accuracy. AL/CR ratio calculated by two meridians showed similar predictive power but with different cutoffs.

Effect modification of time spent outdoors on the association between early childhood overweight and myopia: a one-year follow-up study.

BACKGROUND: This study examined the moderating role of outdoor time on the relationship between overweight and myopia. METHODS: The data for this study was obtained from a prospective study in Shanghai, where non-myopic children wore wristwear and were followed up for 1 year. Eye examinations were performed at each visit. The modification effect was assessed on the additive scale using multivariable logistic regression, and relative excess risk due to interaction was used to calculate the modification effect. RESULTS: A total of 4683 non-myopic children were included with 32.20% being overweight at baseline. Following a 1-year period, 17.42% of children had myopia. When compared to those who spent <90 minutes outdoors, children who spent >120 had a relative risk of myopia onset that was reduced to 0.61. As time spent outdoors decreased, more risks of myopia onset were identified among overweight children than among normal children, the modification effect on the additive scale was -0.007, with ~70% of this effect attributed to the modifying influence of outdoor time. CONCLUSIONS: Increasing outdoor time can reduce myopia more among overweight children than normal. Future interventions should focus on outdoor activities among overweight children to reduce myopia risks.

Impact of the COVID-19 pandemic on the hospital attendance of patients with primary cervical cancer in Heilongjiang, China.

Information regarding the impact of the coronavirus disease 2019 (COVID-19) pandemic on cervical cancer in mainland China is lacking. We explored its impact on the hospital attendance of patients with primary cervical cancer. We included 1918 patients with primary cervical cancer who initially attended Harbin Medical University Cancer Hospital between January 23, 2019, and January 23, 2021. Attendance decreased by 31%, from 1135 in 2019 to 783 in 2020, mainly from January to June (𝜒2 = 73.362, P < .001). The percentage of patients detected by screening decreased from 12.1% in January-June 2019 to 5.8% in January-June 2020 (𝜒2 = 7.187, P = .007). Patients with stage I accounted for 28.4% in 2020 significantly lower than 36.6% in 2019 (𝜒2 = 14.085, P < .001), and patients with stage III accounted for 27.1% in 2020 significantly higher than 20.5% in 2019 (𝜒2 = 11.145, P < .001). Waiting time for treatment was extended from 8 days (median) in January-June and July-December 2019 to 16 days in January-June (𝜒2 = 74.674, P < .001) and 12 days in July-December 2020 (𝜒2 = 37.916, P < .001). Of the 179 patients who delayed treatment, 164 (91.6%) were for the reasons of the healthcare providers. Compared to 2019, the number of patients in Harbin or non-Harbin in Heilongjiang Province and outside the province decreased, and cross-regional medical treatment has been hindered. The COVID-19 pandemic has negatively impacted cervical cancer patient attendance at the initial phase. These results are solid evidence that a strategy and mechanism for the effective attendance of cervical cancer patients in response to public health emergencies is urgently needed.

Axial length changes in progressive and non-progressive myopic children in China.

PURPOSE: Due to pubertal development and crystalline lens compensation, axial length (AL) continues to increase among non-progressive myopic children (absolute annual spherical equivalent (SE) progression less than 0.25 diopter), but the amount is unknown. This study was to investigate the cutoff of AL change to accurately differentiate between progressive and non-progressive myopes. METHODS: A total of 8,546 myopic and treatment-naive children aged 6-10 years were enrolled from two cohort studies. AL with optical biometer and cycloplegic SE with auto refraction were evaluated at baseline and annually. Annual AL change was calculated, and the percentiles of annual axial elongation among progressive and non-progressive myopes were estimated by quantile regression with restricted cubic spline. Area under receiver-operating characteristic (ROC) curve (AUROC), positive predictive value (PPV), and negative predictive value (NPV) were applied to evaluate the accuracy of predicting progressive and non-progressive myopes. RESULTS: Among 8,546 myopic children, 603 (7.06%) were non-progressive myopes. Annual AL changes among non-progressive myopes remained stable with the median annual change being 0.25 mm, while the median for progressive myopes decreased with age from 0.58 to 0.42 mm. AUROC for distinguishing between non-progressive and progressive myopes was 0.88 and was > 0.85 for each age group. Annual AL change, the cutoff of 0.20 mm/year, had significantly high PPV and NPV in predicting progressive myopes with high proportion of progressive myopes and non-progressive myopes with low proportions of progressive myopes. CONCLUSION: Myopic children with non-progressive status had markedly less axial elongation than progressive ones. AL changes with cutoff of 0.20 mm/year could differentiate between non-progressive and progressive status and may be an alternative for evaluating progressive status.

An aspartic protease 47 causes quantitative recessive resistance to rice black-streaked dwarf virus disease and southern rice black-streaked dwarf virus disease.

Rice black-streaked dwarf virus disease (RBSDVD) and southern rice black-streaked dwarf virus disease (SRBSDVD) are the most destructive viral diseases in rice. Progress is limited in breeding due to lack of resistance resource and inadequate knowledge on the underlying functional gene. Using genome-wide association study (GWAS), linkage disequilibrium (LD) decay analyses, RNA-sequencing, and genome editing, we identified a highly RBSDVD-resistant variety and its first functional gene. A highly RBSDVD-resistant variety W44 was identified through extensive evaluation of a diverse international rice panel. Seventeen quantitative trait loci (QTLs) were identified among which qRBSDV6-1 had the largest phenotypic effect. It was finely mapped to a 0.8-1.2 Mb region on chromosome 6, with 62 annotated genes. Analysis of the candidate genes underlying qRBSDV6-1 showed high expression of aspartic proteinase 47 (OsAP47) in a susceptible variety, W122, and a low resistance variety, W44. OsAP47 overexpressing lines exhibited significantly reduced resistance, while the knockout mutants exhibited significantly reduced SRBSDVD and RBSDVD severity. Furthermore, the resistant allele Hap1 of OsAP47 is almost exclusive to Indica, but rare in Japonica. Results suggest that OsAP47 knockout by editing is effective for improving RBSDVD and SRBSDVD resistance. This study provides genetic information for breeding resistant cultivars.

Golden 2-like transcription factor contributes to the major QTL against rice black-streaked dwarf virus disease.

KEY MESSAGE: A major resistance QTL was identified on chromosome 6 in rice variety Wuke; both overexpression and knockdown experiments confirmed that OsGLK1 is the candidate gene for association with Rice black-streaked dwarf virus disease. Rice black-streaked dwarf virus disease is one of the most destructive rice viral diseases in China and East Asia. Progress has been limited in RBSDVD resistance breeding due to inadequate knowledge on the underlying functional genes. In this study, a major QTL for RBSDV (rice black-streaked dwarf virus) independent of SBPH (small brown planthopper) resistance was mapped in a 1.8 Mb interval on chromosome 6 by using an F2:3 population originated from resistant rice variety Wuke. Representative transcripts within this region were analysed and three genes showing amino acid sequence variation in functional domains were selected for transformation. Overexpression experiments showed that one gene exhibited significant enhanced resistance compared to control lines, encoding protein involving Myb domain and probable transcription factor Golden 2-like1 (GLK1). Furthermore, OsGLK1 knockdown rice lines were investigated and the resistance ability was significantly declined without this gene compared to the wild type. Taken together, both overexpression and knockdown experiments strongly suggested that OsGLK1 plays an important role for RBSDV resistance and contributes to the major QTL. The study paves the way for elucidating the molecular mechanism underlying RBSDVD resistance and the molecular markers associated with OsGLK1 may be used for marker-assisted selection.

Rice Stripe Virus Modulates the Feeding Preference of Small Brown Planthopper from the Stems to Leaves of Rice Plants to Promote Virus Infection.

Research on plant-virus-vector interactions has revealed that viruses can enhance their spread to new host plants by attracting nonviruliferous vectors to infected plants or driving viruliferous vectors to noninfected plants. However, whether viruses can also modulate the feeding preference of viruliferous vectors for different plant parts remains largely unknown. Here, by using rice stripe virus (RSV) and its vector, the small brown planthopper (SBPH), as a model, the effect of the virus on the feeding preference of its vector was studied by calculating the number of nonviruliferous and viruliferous SBPHs settling on different parts of rice plants. The results showed that the RSV-free SBPHs significantly preferred feeding on the stems of rice plants, whereas RSV-carrying SBPHs fed more on rice leaves. Moreover, the rice plants inoculated with RSV on the leaves showed more severe symptoms, with enhanced disease incidence and virus accumulation compared with rice plants inoculated at the top and bottom of stems, suggesting that the leaves are more susceptible to RSV than the stems of rice plants. These results demonstrate that RSV modulates the feeding preference of its transmitting vector SBPH from the stems to leaves of rice plants to promote virus infection. Interestingly, we also found that the leaves were more susceptible than the stems to rice black-streaked dwarf virus. This study proves that the feeding preference of insect vectors can be modulated by plant viruses to facilitate virus transmission.

Accommodative responses under various viewing conditions in surgical patients with intermittent exotropia: an institutional, retrospective study.

PURPOSE: To investigate the difference of spherical equivalent (SE) and pupil diameter in adult patients with intermittent exotropia (IXT) under various viewing conditions before and after surgery. METHODS: We retrospectively analyzed the medical records of 23 adult patients who underwent a surgery for IXT. The angle of deviation was measured by the prism and alternative cover test. Refractive error and pupil diameter were measured using the Grand Seiko WAM-5500 open-field autorefractor under binocular and monocular viewing conditions when patients stared at distance (6 m) and near (33 cm). Regression analyses were performed between accommodative load and the angle of deviation. RESULTS: Twenty-three patients (10 males, 13 females) with a mean age of 31.17±8.95 years, of whom 13 (56.5%) had the right eye as the dominant eye. The mean angle of deviation at near and at distance was 69.57±26.37 and 65.43±28.92 prism diopters respectively. There were no significant differences in accommodative response and pupil diameter between the dominant and non-dominant eyes. SE decreased when patients changed from monocular to binocular viewing, and from distant to near viewing (all P< 0.05), so as the pupil diameter (all P< 0.001). During binocular, not monocular viewing, SE was significantly greater after operation than it was before operation (P< 0.001). Accommodative load and pupillary constriction narrowed (p< 0.001) after the operation. Linear regression analysis showed a correlation between the angle of deviation at distance and accommodative load at distance (r2=0.278, p=0.010) and at near (r2=0.332, p=0.005). CONCLUSION: In order to maintain ocular alignment, patients with IXT suffer a large accommodative load, which is related to the angle of deviation. Surgery helps eliminating extra accommodation.

Association between axial length elongation and spherical equivalent progression in Chinese children and adolescents.

BACKGROUND: It is generally believed that a 1-mm axial length (AL) elongation of the eye corresponds to a -3.00 D spherical equivalent (SE) progression, but this is disputed. PURPOSE: To investigate the association between AL elongation and SE progression among children and adolescents. METHODS: A prospective cohort study of 710 children and adolescents aged 6-16 years was included. Ophthalmic examinations, including cycloplegic SE, AL and corneal curvature, were performed at baseline and 1-year follow-up. The ratio of SE change (ΔSE) to AL change (ΔAL) (ΔSE/ΔAL) was calculated, and its association with age and refractive status was explored using a general linear model. RESULTS: Among all participants, 396 (55.77%) were male, with 265 (37.32%) myopes at baseline. The average 1-year ΔSE and ΔAL were 0.61 ± 0.40 D and 0.33 ± 0.22 mm, respectively. Both ΔSE and ΔAL gradually decreased with age (p < 0.001). In the general linear model analyses, age and refractive status were independently associated with ΔSE/ΔAL after adjustment for covariates (age: ß̂$$ \hat{\beta} $$  = 0.04, p < 0.05; myopia vs nonmyopia: ß̂$$ \hat{\beta} $$  = 0.28, p < 0.05). Based on the developed formula ΔSE/ΔAL = 1.74 + 0.05*age (for myopes), mean ΔSE/ΔAL in myopes increased from 2.06 D/mm in the 6-year-olds to 2.59 D/mm in the 16-year-olds. In nonmyopes, ΔSE/ΔAL = 1.33 + 0.05*age, and the ratio increased from 1.65 D/mm in the 6-year-olds to 2.18 D/mm in the 16-year-olds. CONCLUSIONS: The ratio of ΔSE/ΔAL varied with age and refractive status in children and adolescents. The age-specific ΔSE/ΔAL could be used to estimate SE progression through the actual AL change.

A machine learning model to estimate ambient PM2.5 concentrations in industrialized highveld region of South Africa.

Exposure to fine particulate matter (PM2.5) has been linked to a substantial disease burden globally, yet little has been done to estimate the population health risks of PM2.5 in South Africa due to the lack of high-resolution PM2.5 exposure estimates. We developed a random forest model to estimate daily PM2.5 concentrations at 1 km2 resolution in and around industrialized Gauteng Province, South Africa, by combining satellite aerosol optical depth (AOD), meteorology, land use, and socioeconomic data. We then compared PM2.5 concentrations in the study domain before and after the implementation of the new national air quality standards. We aimed to test whether machine learning models are suitable for regions with sparse ground observations such as South Africa and which predictors played important roles in PM2.5 modeling. The cross-validation R2 and Root Mean Square Error of our model was 0.80 and 9.40 µg/m3, respectively. Satellite AOD, seasonal indicator, total precipitation, and population were among the most important predictors. Model-estimated PM2.5 levels successfully captured the temporal pattern recorded by ground observations. Spatially, the highest annual PM2.5 concentration appeared in central and northern Gauteng, including northern Johannesburg and the city of Tshwane. Since the 2016 changes in national PM2.5 standards, PM2.5 concentrations have decreased in most of our study region, although levels in Johannesburg and its surrounding areas have remained relatively constant. This is anadvanced PM2.5 model for South Africa with high prediction accuracy at the daily level and at a relatively high spatial resolution. Our study provided a reference for predictor selection, and our results can be used for a variety of purposes, including epidemiological research, burden of disease assessments, and policy evaluation.

Sirt3 is a novel target to treat sepsis induced myocardial dysfunction by acetylated modulation of critical enzymes within cardiac tricarboxylic acid cycle.

Sepsis induced myocardial dysfunction (SIMD) results in high morbidity and mortality. However, the effective therapeutic strategies for SIMD treatment remain limited. Sirt3 is the main mitochondrial Sirtuin member and is a key modulator of mitochondrial metabolism and function. In this study, we aimed to investigate the effect and mechanism of Sirt3 on SIMD. SIMD was induced by 20 mg/kg Lipopolysaccharides (LPS) injection for 6 h in mice. Sepsis could induce the reduction of cardiac Sirt3 expression and global deficiency of Sirt3 exacerbated cardiac function. Quantitative acetyl-proteomics and cardiac metabolomics analysis revealed that loss of Sirt3 led to hyper-acetylation of critical enzymes within cardiac tricarboxylic acid (TCA) cycle and generation of lactate and NADH, subsequently promotion of cardiac dysfunction after sepsis. Additionally, to evaluate whether Emodin could be utilized as a potential Sirt3 modulator to treat SIMD, male wild type mice (WT mice) or global Sirt3 deficient mice (Sirt3-/- mice) were intraperitoneally injected with 40 mg/kg Emodin for 5 days followed by 20 mg/kg LPS administration for another 6 h and observed that exogenous administration of Emodin could attenuate myocardial dysfunction in septic WT mice. However, septic Sirt3-/- mice can not gain benefit on cardiac performance from Emodin infusion. In conclusion, this study presented the protective role of Sirt3 targeting SIMD, which may provide a potential novel approach to maintain normal cardiac performance after sepsis.

Identification of virus-derived siRNAs and their targets in RBSDV-infected rice by deep sequencing.

RNA interference (RNAi) is a conserved mechanism against viruses in plants and animals. It is thought to inactivate the viral genome by producing virus-derived small interfering RNAs (vsiRNAs). Rice black-streaked dwarf virus (RBSDV) is transmitted to plants by the small brown planthopper (Laodelphax striatellus), and seriously threatens production of rice in East Asia, particularly Oryza sativa japonica subspecies. Through deep sequencing, genome-wide comparisons of RBSDV-derived vsiRNAs were made between the japonica variety Nipponbare, and the indica variety 9311. Four small RNA libraries were constructed from the leaves and shoots of each variety. We found 659,756 unique vsiRNAs in the four samples, and only 43,485 reads were commonly shared. The size distributions of vsiRNAs were mostly 21- and 22-nt long, and A/U bias (66-68%) existed at the first nucleotide of vsiRNAs. Additionally, vsiRNAs were continuously but heterogeneously distributed along S1-S10 segments of the RBSDV genome. Distribution profiles of vsiRNA hotspots were similar in different hosts and tissues, and the 5'- and 3'-terminal regions of S4, S5, and S8 had more hotspots. Distribution and abundance of RBSDV vsiRNAs could be useful in designing efficient targets for exploiting RNA interference for virus resistance. Degradome analysis found 25 and 11 host genes appeared to be targeted by vsiRNAs in 9311 and Nipponbare. We report for the first time vsiRNAs derived from RBSDV-infected rice.

Soluble Egg Antigen Activates M2 Macrophages via the STAT6 and PI3K Pathways, and Schistosoma Japonicum Alternatively Activates Macrophage Polarization to Improve the Survival Rate of Septic Mice.

Sepsis is one of the most challenging health problems worldwide. Our previous study showed that chronic schistosoma japonica (SJ) infection might increase serum anti-inflammatory factors to play a protective role, thus improving the survival rate of septic mice. Further research revealed that SJ infection promoted J774A.1 macrophage differentiation into M2 macrophages; suppressed LPS-induced activation of M1 macrophages; up-regulated CD163, IL-10, and TGF-ß1 expression; inhibited TNF-α and iNOS expression; and blocked the effect of LPS-promoted TNF-α and iNOS expression. Furthermore, adoptive transfer of ex vivo programed M2 macrophages significantly increased the survival rate of septic mice. In vitro studies suggested that soluble egg antigen (SEA) from SJ played the same role as worm infection but had no impact on M1 macrophages. SEA reduced LPS-induced TNF-α and iNOS expression, decreased the inhibitory effect of LPS on IL-10 and TGF-ß1 expression, increased STAT6 phosphorylation, and up-regulated PI3K and Akt expression but inhibited SOCS1 expression. When PI3K inhibitors were added, SEA-induced expression of CD163, IL-10, and arg1 might be reduced. Therefore, worm infection has a protective effect in septic mice in which SEA may play a key role via the STAT6 and PI3K pathways. This finding may provide a favorable solution for the treatment of sepsis, especially early cases. J. Cell. Biochem. 118: 4230-4239, 2017. © 2017 Wiley Periodicals, Inc.

RNA-seq-based digital gene expression analysis reveals modification of host defense responses by rice stripe virus during disease symptom development in Arabidopsis.

BACKGROUND: Virus infection induces and suppresses host gene expression on a global level. Rice stripe virus (RSV) is the type species of the genus Tenuivirus and infects rice and Arabidopsis plants. Microarray-based and next generation sequencing-based transcriptomic approaches have been used to study rice-RSV interactions. However, our knowledge of the response of Arabidopsis plants to RSV infection is limited, and it requires further investigation to determine the similarities (or differences) in virus-host interactions between monocot and dicot hosts infected with RSV. METHODS: We characterized transcriptome changes in Arabidopsis thaliana infected with rice stripe virus (RSV) with RNA-seq based digital gene expression (DGE) analysis. The transcriptomes of RSV-infected samples were compared to those of mock-treated samples at 14 and 21 days post-infection (dpi) during different stages of symptom development. RESULTS: We identified 624 differentially expressed genes (DEGs) in Arabidopsis influenced by RSV at 14 dpi and 21 dpi, among which at 14 dpi, 255 transcripts were induced, and 38 were repressed; at 21 dpi, 146 were induced, and 237 were repressed. Functional annotation indicated that these DEGs were related to multiple biological functions, including defense response, secondary metabolism, protein amino acid phosphorylation and response to abiotic stress. CONCLUSIONS: Importantly, the transcription of genes related to host defense systems was activated by RSV infection at an early stage of symptom development (14 dpi), whereas over the infection period (21 dpi), the host defense response systems were suppressed. A total of 52 genes were continuously differentially expressed between the two time points, indicating that the majority of DEGs were transient and unique to a particular time point during symptom development. The DEGs, particularly the defense response genes, identified in this study are candidates suitable for further functional analysis during the RSV-Arabidopsis interaction.

Glycine bidirectionally regulates ischemic tolerance via different mechanisms including NR2A-dependent CREB phosphorylation.

The exact effect of glycine pre-treatment on brain ischemic tolerance (IT) remains quite controversial. The objective of this study was to investigate the potential effects of glycine on IT. We used rat models of both in vitro ischemia (oxygen and glucose deprivation) and in vivo ischemia (transient middle cerebral artery occlusion). Low doses of glycine (L-Gly) significantly decreased hippocampal ischemic LTP (i-LTP), infarct volume, and neurological deficit scores which were administered before ischemia was induced in rats, whereas high doses of glycine exerted deteriorative effects under the same condition. These findings suggested that exogenous glycine may induce IT in a dose-dependent manner. Furthermore, L-Gly-dependent neuronal protection was inversed by L689, a selective NMDAR glycine site antagonist both in vitro (abolished i-LTP depression) and in vivo (increased infarct size reduction), but not glycine receptor (GlyR) inhibitor strychnine. Importantly, L-Gly-induced IT was achieved by NR2A-dependent cAMP-response element binding protein phosphorylation. These data imply that glycine pre-treatment may represent a novel strategy for inducing IT based on synaptic NMDAR-dependent neuronal transmission. A model of glycine induced dose-dependent bidirectional regulations in ischemic tolerance. (a) Under low dose of Gly pre-treatment, glycine induces NMDAR potentiation and CREB-dependent neuroprotection through the NMDAR co-agonist binding site. (b) Under high dose of Gly pre-treatment, the excessive glycine in synaptic cleft can activate neighboring extrasynaptic sites and combine to the GlyRs. Then, the deteriorative effects would be triggered after NMDAR endocytosis and synaptic depression. AMPAR, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor; CREB, cAMP response element-binding protein; Gly, glycine; GlyR, glycine receptor; GlyT1, gycine transportor 1; NMDAR, N-methyl-d-aspartate receptor.

Assessment of reference gene stability in Rice stripe virus and Rice black streaked dwarf virus infection rice by quantitative Real-time PCR.

BACKGROUND: Stably expressed reference gene(s) normalization is important for the understanding of gene expression patterns by quantitative Real-time PCR (RT-qPCR), particularly for Rice stripe virus (RSV) and Rice black streaked dwarf virus (RBSDV) that caused seriously damage on rice plants in China and Southeast Asia. METHODS: The expression of fourteen common used reference genes of Oryza sativa L. were evaluated by RT-qPCR in RSV and RBSDV infected rice plants. Suitable normalization reference gene(s) were identified by geNorm and NormFinder algorithms. RESULTS: UBQ 10 + GAPDH and UBC + Actin1 were identified as suitable reference genes for RT-qPCR normalization under RSV and RBSDV infection, respectively. When using multiple reference genes, the expression patterns of OsPRIb and OsWRKY, two virus resistance genes, were approximately similar with that reported previously. Comparatively, by using single reference gene (TIP41-Like), a weaker inducible response was observed. CONCLUSIONS: We proposed that the combination of two reference genes could obtain more accurate and reliable normalization of RT-qPCR results in RSV- and RBSDV-infected plants. This work therefore sheds light on establishing a standardized RT-qPCR procedure in RSV- and RBSDV-infected rice plants, and might serve as an important point for discovering complex regulatory networks and identifying genes relevant to biological processes or implicated in virus.

Regulation of recombinant Trichinella spiralis 53-kDa protein (rTsP53) on alternatively activated macrophages via STAT6 but not IL-4Rα in vitro.

Classically activated macrophages (M1) or alternatively activated macrophages (M2) have different functions during helminth infections including Trichinella spiralis (T. spiralis). The excretory/secretory antigens (ESA) of T. spiralis can inhibit macrophage pro-inflammatory cytokines production. However, the specific molecules of ESA that regulate macrophages have not been identified. We previously reported that recombinant T. spiralis derived molecule 53-kDa protein (rTsP53) had protected mice from colitis. Furthermore, in the present study in vitro, we investigated rTsP53 showed anti-inflammatory function by inducing peritoneal macrophages to M2 with expressing M2 molecules of mannose receptor (MR), a novel mammalian lectin (Ym1), arginase-1 (Arg1), and interleukin (IL)-10. Next, we found the effect of rTsP53 on M2 independently of IL-4Rα. But rTsP53 can act dependently on signal transducers and activators of transcription 6 (STAT6). These results further imply that rTsP53 has potential as prospective immuno-therapeutics for inflammatory disorders.

Down-regulation of Aquaporin1 (AQP1) by peptidoglycan via p38 MAPK pathways in primary rat pleural mesothelial cells.

BACKGROUND AND OBJECTIVE: This study was designed to investigate the p38 mitogen-activated protein kinase (MAPK) signaling pathway involved in Aquaporin1 (AQP1) expression caused by staphylococcal peptidoglycan (PGN) in cultured rat pleural mesothelial cells (rPMCs) in vitro. METHODS: RT-PCR and immunoblot analysis were used to determine the relative mRNA and protein levels of AQP1 by PGN in rPMCs. P38 kinase inhibitor SB203580, JNK inhibitor SP600125, and ERK1/2 inhibitor PD98059 were used to determine the effects of PGN-induced AQP1 expression by immunoblot. Activation of p38 by PGN was reflected by detecting the phosphorylation constituent of p38, using immunoblot. The shift of localization after activation of p38 by PGN was investigated by immunofluorescence assay. RESULTS: AQP1 transcription and protein expression were decreased by PGN in dose-dependent and time-dependent manners in rPMCs. Down-regulation of AQP1 by PGN was blocked only by SB203580, neither by SP600125 nor by PD98059. Furthermore, rPMCs exposed to PGN showed activation of p38 MAPK. Phospho-p38 protein production was increased by PGN stimulation in rPMCs. The localization of phospho-p38 was both in the cytosol and nuclei after PGN treatment, while its normal distribution is mainly in the cytosol in rPMCs. CONCLUSION: AQP1 expression was decreased by PGN in both dose-dependent and time-dependent manners in rPMCs. This down-regulation by PGN-induced AQP1 in rPMCs may be mediated by the activation of p38 MARK pathway.