Differential effects of climatic and non-climatic factors on the distribution of vegetation phenology trends on the Tibetan plateau.

The study of vegetation phenology changes is important because it is a sensitive indicator of climate change, affecting the exchange of carbon, energy and water fluxes between the land and the atmosphere. Previous studies have focused on the effects of climatic factors among environmental factors on vegetation phenology, thus the effects of non-climatic factors among environmental factors have not been well quantified. This study endeavors to scrutinize the spatiotemporal inconsistency in the start-of-season (SOS) and the end-of-season (EOS) on the Tibetan Plateau (TP) and to quantify the effects of environmental factors on phenology. To this end, the Moderate-resolution Imaging Spectroradiomater (MODIS) Normalized Difference Vegetation Index (NDVI) data from 2001 to 2018 and four common used methods were employed to extract SOS and EOS, and the site data was used to select the most appropriate phenology results. The Geodetector model was used to assess and measure the explanatory power of different environmental factors. The research results indicate that temperature exerts a more substantial impact on phenology than precipitation on TP. non-climatic factors such as longitude, latitude, and elevation are more influential in determining the distribution of phenological trends than climatic factors. Among these non-climatic factors, latitude has the most prominent effect on the trends of SOS. Furthermore, non-climatic factors exhibit a stronger effect on SOS, whereas EOS is more susceptible to climatic factors and less influenced by non-climatic factors. These discoveries bear great significance in comprehending the intricate outcomes of regional changes on vegetation phenology and enhancing phenology models.

Mapping the occurrence and spatial distribution of noxious weed species with multisource data in degraded grasslands in the Three-River Headwaters Region, China.

The invasion of noxious weed species has long been associated with the degradation of alpine grasslands ecosystems. However, traditional in situ-based methods for surveying noxious weed species are generally time consuming and inefficient over large-scale areas. This paper investigates the possibility of applying multisource data to map the occurrence and spatial distribution of noxious weed species in degraded alpine grasslands in the Three-River Headwaters Region, China. Sentinel-2 image-related vegetation indices (VIs), field sample data and environmental variables were integrated to build a noxious weed species detection model based on the maximum entropy (MaxEnt) species modeling framework. The modeling results suggest that based on both training and testing AUC (area under the receiver operating characteristic (ROC) curve) values higher than 0.82, the VI-only variable model, the environmental-only variable model and the combined environmental and VI variables model, all yielded good simulation results. The spatial distributions of noxious weed species mapped by the VI-only variable model and the combined environmental and VI variable model were more concentrated, while the VI-only variable model yielded more scattered results. This analysis also explains why noxious weed species are mainly distributed in the low-elevation flat riverine zone in the study area. The model combining Sentinel-2 imagery-related VIs, environmental variables and in situ sample data proposed in this study can successfully map the occurrence and spatial distributions of noxious weed species. The method and results of this research can be used to help monitor noxious weed species invasions and better manage grassland ecosystems.

Polystyrene microplastics lead to pyroptosis and apoptosis of ovarian granulosa cells via NLRP3/Caspase-1 signaling pathway in rats.

Microplastics (MPs) considered as a new persistent environmental pollutant could enter into the circulatory system and result in decrease of sperm quantity and quality in mice. However, the effects of Polystyrene MPs (PS MPs) on the ovary and its mechanism in rats remained unclear. In this present study, thirty-two healthy female Wistar rats were exposed to different concentrations of 0.5 µm PS MPs dispersed in deionized water for 90 days. Using hematoxylin-eosin (HE) staining, the number of growing follicles was decreased compared to the control group. In addition, the activity of glutathione peroxidase (GSH-Px), catalase (CAT) and superoxide dismutase (SOD) were decreased while the expression level of malondialdehyde (MDA) was increased in ovary tissue. Confirmed by immunohistochemistry, the integrated optical density of NLRP3 and Cleaved-Caspase-1 had been elevated by 13.9 and 14 in granulosa cells in the 1.5 mg/kg/d group. Furthermore, compared to the control group, the level of AMH had been decreased by 23.3 pg/ml while IL-1ß and IL-18 had been increased by 32 and 18.5 pg/ml in the 1.5 mg/kg/d group using the enzyme-linked immune sorbent assay (ELISA). Besides, the apoptosis of granulosa cells was elevated measured by terminal deoxyribonucleotide transferase-mediated nick end labeling (TUNEL) staining and flow cytometry. Moreover, western blot assays showed that the expressions of NLRP3/Caspase-1 signaling pathway related factors and Cleaved-Caspase-3 were increased. These results demonstrated that PS MPs could induce pyroptosis and apoptosis of ovarian granulosa cells via the NLRP3/Caspase-1 signaling pathway maybe triggered by oxidative stress. The present study suggested that exposure to microplastics had adverse effects on ovary and could be a potential risk factor for female infertility, which provided new insights into the toxicity of MPs on female reproduction.

Polystyrene microplastics cause granulosa cells apoptosis and fibrosis in ovary through oxidative stress in rats.

Microplastics (MPs) are receiving increased attention as a harmful environmental pollutant. Studies have investigated that MPs have reproductive toxicity, but the mechanism is little known. Here, we aimed to investigate the effects of polystyrene microplastics (PS-MPs) on ovary in rats and the underlying molecular mechanisms. in vivo, thirty-two female Wistar rats were exposed to 0.5 µm PS-MPs at different concentrations (0, 0.015, 0.15 and 1.5 mg/d) for 90 days. And then, all animals were sacrificed, ovaries and blood were collected for testing. in vitro, granulosa cells (GCs) were separated from rat ovary and treated with 0、1、5、25 µg/mL PS-MPs and reactive oxygen species (ROS) inhibitor N-Acetyl-l-cysteine (NAC) respectively. Our results showed that PS-MPs could enter into GCs and result in the reducing of growing follicles number. And the Enzyme-linked immunosorbent assay (ELISA) manifested that PS-MPs could obviously decrease the level of anti-Müllerian hormone (AMH). In addition, PS-MPs induced oxidative stress, apoptosis of GCs and ovary fibrosis evidenced by assay kits, flow cytometry, immunohistochemistry, Masson's trichrome and Sirius red staining. Moreover, the western blot assay manifested that PS-MPs exposure significantly increased the expression levels of Wnt/ß-Catenin signaling pathways-related proteins (Wnt, ß-catenin, p-ß-catenin) and the main fibrosis markers (transforming growth factor-ß (TGF-ß), fibronectin, α-smooth muscle actin (α-SMA). Additionally, the expression levels of Wnt and p-ß-catenin, apoptosis of GCs decreased after NAC treatment. In summary, polystyrene microplastics cause fibrosis via Wnt/ß-Catenin signaling pathway activation and granulosa cells apoptosis of ovary through oxidative stress in rats, both of which ultimately resulted in decrease of ovarian reserve capacity.

Characterization of the nuclear localization sequence of beak and feather disease virus capsid proteins and their assembly into virus-like particles.

Beak and feather disease virus (BFDV) is a single-stranded circular DNA icosahedral virus that belongs to the Circoviridae family. This virus is the causative pathogen of beak and feather disease, which leads to feather loss, malformed claws, and immunosuppression of psittacine birds. Our study produced BFDV virus-like particles (VLPs) including capsid proteins, mutant Cap proteins (Cap ΔNLS54, Cap ΔNLS62, Cap C228S, and Cap ΔNES) and chimeric Cap proteins carrying the epitope (amino acid residues 64-70) of the replication-associated protein (R-Cap, Cap-R, R-Cap ΔNLS54, and Cap ΔNLS54-R). All of the aforementioned VLPs were observed via transmission electron microscopy and verified through immunogold labeling. The nuclear localization sequence (NLS) of the Cap protein was identified between amino acid residues 55-62. Nuclear export of the Cap protein depended on the nuclear export sequence (NES). All VLPs except Cap ΔNLS62 and Cap ΔNES entered the cells 2 h post-infection (hpi) and were shuttled into the nucleus at 8 hpi. Wheat germ agglutinin (WGA) blocked the nuclear entry of Cap proteins at 8 hpi and the nuclear export of Cap proteins at 16 hpi was inhibited by leptomycin B. The nuclear entry of Cap protein was inhibited by importin α and importin ß inhibitors, as well as NLS peptides. Moreover, the interactions of Cap proteins and Cap VLPs with both importin α and importin ß were characterized via the GST pull-down and immunofluorescence assays. These interactions were blocked by the presence of importin α and importin ß inhibitors, as well as NLS peptides. Therefore, our study is the first to describe the precise position of the NLS of the BFDV Cap protein and the interaction of Cap protein with importin α and importin ß in vitro.

Newborn screening for Morquio disease and other lysosomal storage diseases: results from the 8-plex assay for 70,000 newborns.

BACKGROUND: The necessity of early treatment for lysosomal storage diseases (LSDs) has triggered the development of newborn screening for LSDs in recent years. Here we report the first 70,000 newborns screened for Mucopolysaccharidosis (MPS) type 4A (Morquio syndrome) and other LSDs by an 8-plex assay including the original 4-plex LSD screening tandem mass spectrometry (MS/MS) assay for Pompe disease, Fabry disease, Gaucher disease, and MPS I disease. METHODS: The additional reaction for MPS II, MPS 3B, MPS 4A, and MPS 6 enzymes was performed separately from the 4-plex reaction. The two reactions were quenched and extracted, then combined before carrying out a single 2-min UPLC-MS/MS analysis. RESULTS: From Mar. 2018 to Apr. 2019, 73,743 newborns were screened with the 8-plex LSD screening assay. The 8-plex assay revealed a better analytical precision than the previous 4-plex assay possibly because the 8-plex was carried out using UPLC-MS/MS. Six newborns were found to have low MPS-4A enzyme (N-acetylgalactosamine-6-sulfatase) activity and biallelic GALNS pathogenic mutations in trans; these patients are presumably affected with MPS4A, making an incidence of one in 12,291 (95% confident interval (CI): 5633-26,817). One mutation, c.857C > T (p.T286 M) of the GALNS gene, accounted 5 of the 12 mutated alleles. These newborns had immature vertebral bodies at 1 month of age, and one case was treated with elosulfase alfa 2 mg/kg/week starting from 4 months of age. Among other MPSs screened, one case of MPS I, 3 cases of MPS II, and 3 cases of MPS 3B were detected. One case of mucolipidosis type III was also diagnosed. In conjunction with another 9 patients of Pompe disease, Gaucher disease, and classical Fabry disease, making an incidence of LSDs as one in 3206 newborns (95% CI: 2137 - 4811). The one with infantile-onset Pompe disease and the one with Gaucher disease were treated since the age of 8 days and 41 days respectively. CONCLUSIONS: Routine newborn screening of MPS 4A and other LSDs were made possible by the 8-plex LSD screening assay. However, detailed phenotype prediction and the time to start treatment will need further elucidation.

Phylogeography and paleodistribution models of a widespread birch (Betula platyphylla Suk.) across East Asia: Multiple refugia, multidirectional expansion, and heterogeneous genetic pattern.

Widespread tree species cover large geographical areas and play important roles in various vegetation types. Understanding how these species responded to historical climatic changes is important for understanding community assembly mechanisms with evolutionary and conservation implications. However, the location of refugial areas and postglacial history of widespread trees in East Asia remain poorly known. We combined microsatellite data (63 populations, 1756 individuals) and ecological niche modeling to examine the range-wide population diversity, genetic structure, and historical demography of a pioneer tree species, Asian white birch (Betula platyphylla Suk.) across East Asia. We found a north-to-south trend of declining genetic diversity and five clusters, corresponding to geographical regions. Different clusters were inferred to have diverged through Pleistocene climatic oscillations and have different expansion routes, leading to genetic admixture in some populations. Ecological niche models indicated that the distribution of B. platyphylla during the last glacial maximum still had a large latitude span with slight shifts toward southeast, and northern populations had more variable distribution ranges than those in the south during later climatic oscillations. Our results reflect the relatively stable distribution through the last glacial-interglacial cycles and recent multidirectional expansion of B. platyphylla, providing new hypotheses for the response pattern of widespread tree species to climate change. The gradual genetic pattern from northeast to southwest and alternative distribution dynamics possibly resulted from environmental differences caused by latitude and topographic heterogeneity.

Characterization of Wnt1-inducible Signaling Pathway Protein-1 in Obese Children and Adolescents.

Wnt1-inducible signaling pathway protein-1 (WISP1), a member of the CCN family, is increasingly being recognized as a potential target for obesity and type 2 diabetes mellitus. Recent studies have shown that WISP1 can regulate low-grade inflammation in obese mice, and circulating WISP1 levels are associated with obesity and type 2 diabetes mellitus in adults. Herein, we measured serum WISP1 levels in obese youth and explored its relationships with pro-inflammatory cytokine interleukin 18 (IL-18) and other metabolic indexes. Totally, 44 normal-weight and 44 obese children and adolescents were enrolled. Physical and laboratory data were recorded, and then serum levels of WISP1 and IL-18 were determined by enzyme-linked immunosorbent assays. Results showed that serum levels of WISP1 were significantly higher in obese children and adolescents than in normal-weight healthy controls (1735.44±15.29 vs. 1364.08±18.69 pg/mL). WISP1 levels were significantly positively correlated with body mass index (BMI) and BMI z-score (r=0.392, P=0.008; r=0.474, P=0.001, respectively) in obese group; circulating IL-18 was increased in obese individuals (1229.06±29.42 vs. 295.87±13.30 pg/mL). Circulating WISP1 levels were significantly correlated with IL-18 (r=0.542, P<0.001), adiponectin (r=0.585, P<0.001) and leptin (r=0.592, P<0.001). The multivariate stepwise regression analysis showed that higher IL-18 levels represented the main determinant of increased WISP1 levels after adjusting for BMI, waist circumference, fasting insulin, homeostatic model assessment of insulin resistance (HOMA-IR) and HbA1c in obese individuals (ß=0.542, P=0.000). WISP1 can be involved in glucose/lipid metabolism in obese youth, which may be modulated by IL-18. Increased WISP1 levels may be a risk factor of obesity and insulin resistance, and WISP1 has a potential therapeutic effect on insulin resistance in obese children and adolescents.

Impacts of the removal of shrubs on the physiological and biochemical characteristics of Syntrichia caninervis Mitt: in a temperate desert.

Moss crusts play important roles in biological soil crusts biomass and soil surface stabilization. However, because of increasingly intensive human activities, especially grazing, the growth and survival of shrubs are seriously threatened. This study aimed to test whether the presence of shrubs affects the physiological state of the bryophyte Syntrichia caninervis Mitt. in this desert ecosystem. We simulated animal-grazed shrubs at three levels in the Gurbantunggut Desert and compared these simulations to exposed areas, measuring the indicators of growth and stress tolerance exhibited by bryophytes. The results showed that the removal of shrubs significantly decreased chlorophyll fluorescence activity and soluble protein content in S. caninervis, especially under the total shrub removal treatment. The ratio between the total removal of shrubs and other treatments in antioxidative enzymes and in osmotic adjustment substances of S. caninervis exhibited two types of responses. With the exception of malonyldialdehyde (MDA) and superoxide dismutase (SOD), the variables examined fitted as downward parabolic then upward parabolic temporal dynamics. The removal of shrubs is harmful to the survival of S.caninervis. In resource-constrained conditions, SOD is an important antioxidant enzyme that of peroxidase (POD), catalase (CAT) and osmotic adjustment substances, for S. caninervis survival.

Vegetation dynamics and its driving forces from climate change and human activities in the Three-River Source Region, China from 1982 to 2012.

The Three-River Source Region (TRSR), a region with key importance to the ecological security of China, has undergone climate changes and a shift in human activities driven by a series of ecological restoration projects in recent decades. To reveal the spatiotemporal dynamics of vegetation dynamics and calculate the contributions of driving factors in the TRSR across different periods from 1982 to 2012, net primary productivity (NPP) estimated using the Carnegie-Ames-Stanford approach model was used to assess the status of vegetation. The actual effects of different climatic variation trends on interannual variation in NPP were analyzed. Furthermore, the relationships of NPP with different climate factors and human activities were analyzed quantitatively. Results showed the following: from 1982 to 2012, the average NPP in the study area was 187.37gcm(-2)yr(-1). The average NPP exhibited a fluctuation but presented a generally increasing trend over the 31-year study period, with an increase rate of 1.31gcm(-2)yr(-2). During the entire study period, the average contributions of temperature, precipitation, and solar radiation to NPP interannual variation over the entire region were 0.58, 0.73, and 0.09gcm(-2)yr(-2), respectively. Radiation was the climate factor with the greatest influence on NPP interannual variation. The factor that restricted NPP increase changed from temperature and radiation to precipitation. The average contributions of climate change and human activities to NPP interannual variation were 1.40gcm(-2)yr(-2) and -0.08gcm(-2)yr(-2), respectively. From 1982 to 2000, the general climate conditions were favorable to vegetation recovery, whereas human activities had a weaker negative impact on vegetation growth. From 2001 to 2012, climate conditions began to have a negative impact on vegetation growth, whereas human activities made a favorable impact on vegetation recovery.

The CD14--159C/T polymorphisms and the risks of tuberculosis: a meta-analysis.

Previous studies about the association between CD14--159C/T polymorphisms and the risks of tuberculosis (TB) have yielded conflicting results, and thus a meta-analysis was performed in order to provide a more accurate estimation. A computerized literature search with additional manual search was conducted for the relevant available studies. Pooled odds ratio (ORs) and 95% confidence intervals (95%CIs) were calculated by either fixed-effects model or random-effects model based on heterogeneity test. A total of 8 eligible studies (1729 cases and 1803 controls) were included in the meta-analyses. Overall, a significant association between CD14--59C/T polymorphism and TB risks was detected in the recessive model (TT vs. TC/CC, OR=1.48, 95%CI 1.06-2.07). Significant associations were also detected in Asians (T vs. C, OR=1.49, 95%CI 1.33-1.67; TT vs. CC, OR=1.94, 95%CI 1.54-2.45; TT vs. TC/CC: OR=1.86, 95%CI 1.57-2.20). In contrast, no significant association was detected in Caucasians in each genetic model. The subgroup analysis stratified by TB types showed a significant association between CD14--159C/T polymorphism and pulmonary TB risks (T vs. C, OR=1.51, 95%CI 1.01-2.26; TT vs. TC/CC, OR=1.84, 95%CI 1.03-3.29), which did not reach statistically significance when the P values were Bonferroni adjusted to 0.025. No publication bias was detected in any comparisons. Collectively, the results of this meta-analysis suggest a possible association between CD14--59C/T polymorphism and TB risks in Asians, but not in Caucasians. Well-designed case-control studies with larger sample size are needed to confirm these results.

Developmental changes in the expression of Kiss1 gene and estrogen receptor α gene in hypothalamus of female Sprague-Dawley rats / 中华实用儿科临床杂志

Objective To investigate the function of Kiss1 gene and estrogen receptor α gene (ERα gene) in puberty of rats,by detecting the expressions of Kiss1 mRNA and ERα mRNA in the hypothalamus and the serum luteinizing hormone (LH) and estradiol (E2) level of female Sprague-Dawley (SD) rats at various stage of development with Real-time PCR and enzyme-linked immunosorbent assay(ELISA).Methods Thirty-five female SD rats of 3 days were weaned on postnatal(PND)22 and then the vaginal opening condition was observed daily.The rats were sacrificed at PND 15(juvenile group,n =19) and PND 35 (pubertal group,n =16).The hypothalamus were segregated and the serum were extracted from heart blood.All of the samples were stored at-80 ℃ prepared.Then the mRNA were extracted from the hypothalamus and the cDNA obtained by reverse transcription were tested with real-time PCR.The relative mRNA expression level of Kiss1 gene and ERα gene were calculated.Results 1.Entire level:it was found that the pubertal group vaginal opening time was (32.1 ± 1.0) days,while the juvenile group was not found with vaginal opening until sacrificed.2.Real-time PCR:the expressions of Kiss1 and ERα gene were significantly increased in pubertal group (Kissl gene:5.39-± 2.52,ERα gene:1.57 ±1.87) compared with juvenile group(Kiss1 gene:1.06 ± 1.09,ERα gene:0.59-± 0.68),and the differences were statistically significant (all P ＜ 0.001).3.ELISA:the serum LH and E2 in pubertal group [LH (11.61 ± 0.95) IU/L,E2 (167.53 ± 31.09) ng/L] were significantly higher than LH [(5.46-± 1.89)IU/L] and E2 [(58.59 ± 29.96) ng/L] in juvenile group,and the differences were statistically significant (all P ＜0.001).Conclusion Kiss1 gene and ERα gene are involved in the start of the sexual development of female SD rat.

Adjuvant transarterial chemoembolization after curative resection of hepatocellular carcinoma: a non-randomized comparative study.

BACKGROUND/AIMS: Prevention of recurrence is the most important strategy to improve long-term survival after resection of hepatocellular carcinoma (HCC). This comparative study aimed to evaluate the outcome of adjuvant transarterial chemoembolization (TACE) after hepatectomy. METHODOLOGY: From February 1996 and September 2001, 721 consecutive patients (adjuvant TACE treatment vs. control group; 145 vs. 576) with R0 resection for HCC were analyzed. The prospective data was analyzed retrospectively. RESULTS: After a median follow-up of 75 months, 89 patients (61.4%) in the adjuvant TACE group and 355 patients (61.6%) in the control group had recurrent disease. There was no significant difference in the tumor recurrence rate between the 2 groups. There was significant difference in the tumor recurrence time between the 2 groups. The 1-, 3- and 5-year overall survival rates were 96.5%, 70.0% and 55.9%, respectively, for the adjuvant TACE group and 80.8%, 49.7% and 38.8%, respectively, for the control group. The 1-, 3- and 5-year disease-free survival rates were 79.9%, 54.9% and 48.4%, respectively, for the adjuvant TACE group and 60.2%, 39.8% and 31.5%, respectively, for the control group. The differences in the disease-free survival rates and the overall survival rates between the 2 groups were significant. In subgroup analysis, there was significant survival benefit in the adjuvant TACE group in the subgroup of patients with risk factors of recurrence - large tumor size, presence of satellite tumor nodules and narrow resection margin. CONCLUSIONS: Adjuvant TACE improved surgical outcome in those patients with risk factors of HCC recurrence.

Gastrodia elata decreases isoprenaline potency and enhances spontaneous phasic activity in the rat detrusor.

Gastrodia elata (Tianma) is a traditional Chinese herb with demonstrated vasodilatory effects. This pilot study examined the effects of Tianma treatment on bladder smooth muscle contractility. Rats were treated with 2.5 g Tianma per kg body weight over 7 weeks. Contractility was measured in detrusor strips isolated in both transverse (Tr) and longitudinal (Lg) directions with the urothelium intact (+UE) or denuded (-UE). Spontaneous phasic activity was enhanced in longitudinal +UE strips. No differences between control and Tianma-treated detrusor strips were detected in contractions elicited by K+-Krebs' solution or carbachol. Isoprenaline (IPNA)-induced relaxation remained unchanged in -UE strips after Tianma treatment. However, potency of IPNA was lower in Tianma-treated +UE strips in the longitudinal direction. These findings provided an initial assessment of how Tianma altered bladder smooth muscle function. It will be of interest in future investigations to elucidate the mechanisms via which Tianma exerts its actions on the bladder.

Modelling population growth on public water and sanitation facilities using GIS and statistics: a case study of Aboabo, Ghana.

BACKGROUND: Effect of population increase on public water and sanitation facilities in densely populated area, Aboabo, Kumasi, Ghana. MATERIALS AND METHODS: Town sheet maps, layout and population census data of Aboabo. GPS for observing spatial locations existing water and sanitation facilities and field verification exercise in the study. GIS for building geodatabase, digitization and Cartographic Visualization. Questionnaires were used to collect non-spatial information on the sanitation facilities and all public facilities. RESULTS: GIS and a Statistical Approach have been respectively used to develop cartographic and mathematical models to analyse, predict and visualize the effect of population increase on public water and sewage facilities in densely populated area. The developed mathematical models correlates with the population at each instance to the required number of water accessible points or standing pipes as well as the number of required public toilet (sewage) facilities. The cartographic and mathematical models provides an efficient and effective means of mitigating diseases associated with water and sanitation; and informs planners and assembly members of the effects of increasing population on public facilities for proper future planning and geospatial decision making; and to ensure proper infrastructural management at the community levels. CONCLUSIONS: Effective decision support systems for analysing, predicting and visualizing public water and sewage facilities in densely populated area. Draws the awareness of the government, concerned groups and non-Governmental Organizations (NGO's) to the extreme detrimental effect that the increase in population has, especially on public water and sewage facilities and how it can be managed at the community level.

Glucagon-like peptide 1 based therapy for type 2 diabetes.

BACKGROUND: Incidence of type 2 diabetes mellitus (T2DM) has increased in young people in recent years and new therapies are required for its effective treatment. Glucagon-like peptide 1 (GLP-1) is a potent blood glucose-lowering hormone produced in the L cells of the intestine. It may be potentially effective in the treatment of hyperglycemia in patients with T2DM. DATA SOURCES: PubMed database were searched with the terms "GLP-1", "incretins" and "diabetes". RESULTS: GLP-1 is a product of the glucagon gene, and its secretion is controlled by both neural and endocrine signals. GLP-1 lowers plasma glucose by stimulating insulin and suppressing secretion of glucagons, thus inhibiting gastric emptying and reducing appetite. GLP-1 exerts these actions by the engagement of structurally distinct G-protein-coupled receptors (GPCRs). In patients with T2DM, GLP-1 increases insulin secretion and normalizes both fasting and postprandial blood glucose when given as a continuous intravenous infusion. However, the native hormone is unsuitable as a drug because it is broken down rapidly by dipeptidyl peptidase IV (DPP-4) and cleared by the kidneys. Fortunately, many GLP-1 agonists or analogues and DPP-4 inhibitors have been found or developed, such as exendin-4, exenatide, liraglutide, CJC1131, vidaliptin and P32/98. Clinical trials have shown their therapeutic functions in T2DM with little adverse reaction. CONCLUSION: A GLP-1 based therapy will be safe and effective for the treatment of T2DM.

[Pathogenesis of retinal neovascularization in a rat model of oxygen fluctuations-induced retinopathy].

OBJECTIVE: Fluctuations in arterial oxygen are associated with development of severe retinopathy of prematurity (ROP) in humans. However, the causal relationship between oxygen variability and ROP remains unknown. The authors developed a rat model of retinal neovascularization by repeated fluctuations of inhaled oxygen between hypoxia and hyperoxia to investigate the mechanism of the development of retinal neovascularization, the regulation of vascular endothelial growth factor (VEGF) and KDR/Flk-1 (VEGFR-2) expression. METHODS: Two hundred and eight newborn Sprague Dawley rats were randomly divided into oxygen and air groups. The oxygen concentration in the oxygen group was alternated between 50% and 10% every 24 hours for 14 days. The control group were kept in room air environment. VEGF and Flk-1 expression was observed at 14, 18 and 25 days after birth in both exposed group and control group by immunohistochemical staining and semiquantitative RT-PCR. The status of retinal vasculature on day 4 after oxygen exposure was also observed. The retinas were dissected and stained by using a histochemical method for detecting adenosine diphosphatase (ADPase) activity, digital images of the retinas were captured and the peripheral avascular retina were measured. HE staining on methacrylate sections of eyes was used for counting the number of nuclei extending from retinal area into vitreous to identify extraretinal neovascularization. Numeric data were expressed as the mean +/- standard deviation (SD). Statistical calculations were performed using the SAS 8.1 statistical package. Differences in measured variables between experimental and control groups were determined using comparison of the means using two-way analysis of variance (ANOVA) statistical calculations and T-test. AP value less than 0.05 was regarded as significant. RESULTS: (1) The animal model was successfully established: the avascular areas of retina of 18-day-old rats were larger than those of the control group and the numbers of nuclei extending from retinal area into vitreous in exposed group were significantly higher compared to the control (P < 0.05). (2) The expression of VEGF and Flk-1 on the 14(th) day in the oxygen group was significantly stronger than that of the control group (P < 0.05). In the oxygen group, VEGF and Flk-1 expression was the strongest in the retina on the 18(th) day, the result had significant difference as compared with the 14(th) and 25(th) day (P < 0.05), and they were also stronger than that of the control group (P < 0.05). The expression of VEGF and Flk-1 decreased on the 25(th) day and had no significant difference as compared with the control group (P > 0.05). (3) Both VEGF-mRNA and Flk-1-mRNA significantly increased on the 14(th) day and the 18th day (P < 0.05). On the 25(th) day, the amounts of VEGF-mRNA and Flk-1-mRNA were similar between the control and oxygen group (P > 0.05). CONCLUSION: Fluctuation in oxygen is associated with the development of retinal neovascularization in the retinopathy. Increased expressions of VEGF and Flk-1 in the oxgen fluctuations-induced neovascularized retina suggested that VEGF and Flk-1 might play a critical role in the pathogenesis of ROP. The results also indicated the positive feedback in the pathogenesis of ROP that the synergistic interaction of VEGF and Flk-1 in the retinal vascular proliferation. These findings provide insight into the effect of repeated oxygen fluctuation on the development of severe ROP in preterm infants.

Pathogenesis of retinal neovascularization in a rat model of oxygen fluctuations-induced retinopathy / 中华儿科杂志

<p><b>OBJECTIVE</b>Fluctuations in arterial oxygen are associated with development of severe retinopathy of prematurity (ROP) in humans. However, the causal relationship between oxygen variability and ROP remains unknown. The authors developed a rat model of retinal neovascularization by repeated fluctuations of inhaled oxygen between hypoxia and hyperoxia to investigate the mechanism of the development of retinal neovascularization, the regulation of vascular endothelial growth factor (VEGF) and KDR/Flk-1 (VEGFR-2) expression.</p><p><b>METHODS</b>Two hundred and eight newborn Sprague Dawley rats were randomly divided into oxygen and air groups. The oxygen concentration in the oxygen group was alternated between 50% and 10% every 24 hours for 14 days. The control group were kept in room air environment. VEGF and Flk-1 expression was observed at 14, 18 and 25 days after birth in both exposed group and control group by immunohistochemical staining and semiquantitative RT-PCR. The status of retinal vasculature on day 4 after oxygen exposure was also observed. The retinas were dissected and stained by using a histochemical method for detecting adenosine diphosphatase (ADPase) activity, digital images of the retinas were captured and the peripheral avascular retina were measured. HE staining on methacrylate sections of eyes was used for counting the number of nuclei extending from retinal area into vitreous to identify extraretinal neovascularization. Numeric data were expressed as the mean +/- standard deviation (SD). Statistical calculations were performed using the SAS 8.1 statistical package. Differences in measured variables between experimental and control groups were determined using comparison of the means using two-way analysis of variance (ANOVA) statistical calculations and T-test. AP value less than 0.05 was regarded as significant.</p><p><b>RESULTS</b>(1) The animal model was successfully established: the avascular areas of retina of 18-day-old rats were larger than those of the control group and the numbers of nuclei extending from retinal area into vitreous in exposed group were significantly higher compared to the control (P < 0.05). (2) The expression of VEGF and Flk-1 on the 14(th) day in the oxygen group was significantly stronger than that of the control group (P < 0.05). In the oxygen group, VEGF and Flk-1 expression was the strongest in the retina on the 18(th) day, the result had significant difference as compared with the 14(th) and 25(th) day (P < 0.05), and they were also stronger than that of the control group (P < 0.05). The expression of VEGF and Flk-1 decreased on the 25(th) day and had no significant difference as compared with the control group (P > 0.05). (3) Both VEGF-mRNA and Flk-1-mRNA significantly increased on the 14(th) day and the 18th day (P < 0.05). On the 25(th) day, the amounts of VEGF-mRNA and Flk-1-mRNA were similar between the control and oxygen group (P > 0.05).</p><p><b>CONCLUSION</b>Fluctuation in oxygen is associated with the development of retinal neovascularization in the retinopathy. Increased expressions of VEGF and Flk-1 in the oxgen fluctuations-induced neovascularized retina suggested that VEGF and Flk-1 might play a critical role in the pathogenesis of ROP. The results also indicated the positive feedback in the pathogenesis of ROP that the synergistic interaction of VEGF and Flk-1 in the retinal vascular proliferation. These findings provide insight into the effect of repeated oxygen fluctuation on the development of severe ROP in preterm infants.</p>