Effect of ofloxacin levels on growth, photosynthesis and chlorophyll fluorescence kinetics in tomato.

Antibiotic pollution has become a global environmental pollution problem. Chlorophyll fluorescence is one of the most important indicators reflecting the degree to which plants are influenced by the environment. Ofloxacin (OFL) is a highly toxic antibiotic pollutant, and there are few reports on the effects of changes in OFL levels on tomato chlorophyll fluorescence parameters. In this study, we investigated the responses of tomato growth, photosynthetic activity and chlorophyll fluorescence kinetics to exogenous OFL exposure (as the concentrations of 0, 2.5, 5, 10 and 20 mg L-1). The results showed that lower concentrations of OFL (2.5 mg L-1) had little impact on tomato growth, while plant growth was inhibited with the OFL concentration increasing. At higher OFL concentrations (5, 10 and 20 mg L-1), chloroplasts ruptured, and chlorophyll became degraded, resulting in leaf etiolation. Furthermore, the photosynthetic and photochemical efficiency and electron transfer rate were significantly inhibited by OFL. Moreover, damage to the oxygen-evolving complex on the donor side of PSⅡ prevented electron transfer from QA to QB and led to photoinhibition. In conclusion, higher OFL concentration reduced photosynthesis by destroying the photosynthetic mechanism in tomato, resulting in tomato leaf etiolation and plant growth inhibition.

The Chemokines Initiating and Maintaining Immune Hot Phenotype Are Prognostic in ICB of HNSCC.

Background: The immune checkpoint blockade (ICB) with anti-programmed cell death protein 1(PD-1) on HNSCC is not as effective as on other tumors. In this study, we try to find out the key factors in the heterogeneous tumor-associated monocyte/macrophage (TAMM) that could regulate immune responses and predict the validity of ICB on HNSCC. Experimental Design: To explore the correlation of the TAMM heterogeneity with the immune properties and prognosis of HNSCC, we established the differentiation trajectory of TAMM by analyzing the single-cell RNA-seq data of HNSCC, by which the HNSCC patients were divided into different sub-populations. Then, we exploited the topology of the network to screen out the genes critical for immune hot phenotype of HNSCC, as well as their roles in TAMM differentiation, tumor immune cycle, and progression. Finally, these key genes were used to construct a neural net model via deep-learning framework to predict the validity of treatment with anti-PD-1/PDL-1 Results: According to the differentiation trajectory, the genes involved in TAMM differentiation were categorized into early and later groups. Then, the early group genes divided the HNSCC patients into sub-populations with more detailed immune properties. Through network topology, CXCL9, 10, 11, and CLL5 related to TAMM differentiation in the TME were identified as the key genes initiating and maintaining the immune hot phenotype in HNSCC by remarkably strengthening immune responses and infiltration. Genome wide, CASP8 mutations were found to be key to triggering immune responses in the immune hot phenotype. On the other hand, in the immune cold phenotype, the evident changes in CNV resulted in immune evasion by disrupting immune balance. Finally, based on the framework of CXCL9-11, CLL5, CD8+, CD4+ T cells, and Macrophage M1, the neural network model could predict the validity of PD-1/PDL-1 therapy with 75% of AUC in the test cohort. Conclusion: We concluded that the CXCL9, 10,11, and CCL5 mediated TAMM differentiation and constructed immune hot phenotype of HNSCC. Since they positively regulated immune cells and immune cycle in HNSCC, the CXCL9-11 and CCL5 could be used to predict the effects of anti-PD-1/PDL-1 therapy on HNSCC.

Platelets fine-tune effector responses of naïve CD4+ T cells via platelet factor 4-regulated transforming growth factor ß signaling.

BACKGROUND AND AIM: Platelets are an able regulator of CD4+ T cell immunity. Herein, the mechanisms underlying platelet-regulated effector responses of naïve CD4+ T (Tn) cells were investigated. METHODS: Platelet-Tn cell co-cultures of human cells, genetically modified murine models, and high-throughput bioinformatic analyses were combined to elucidate molecular mechanisms of platelet-dependent regulation. RESULTS: Platelets exerted sophisticated regulation on effector responses of type 1, 2, and 17 T helper (Th1/Th2/Th17) and regulatory T (Treg) cells, in time-, concentration-, and organ-dependent manners and with close cooperation of transforming growth factor ß (TGFß) and platelet factor 4 (PF4). PF4 at low concentrations reinforced TGFß signaling by heteromerizing with type III TGFß receptor (TGFBRIII), and subsequently enhanced TGFBRII expression and TGFß signaling. High-concentration PF4 had, however, opposite effects by directly binding to TGFBRII, blocking TGFß-TGFBRII ligation, and thus inhibiting TGFß signaling. Furthermore, platelet depletion markedly hampered Treg and Th17 responses in the spleen but not in the lymph nodes, blockade of platelet-Tn cell contact diminished platelet effects, while spleen injection of PF4-immobilized microparticles in PF4-deficient mice mimicked platelet effects, suggesting the importance of direct platelet-Tn contact and platelet-bound PF4 for the optimal regulatory effects by platelets. CONCLUSION: Platelets exert context-dependent regulations on effector responses of Tn cells via PF4-TGFß duet, suggesting new possibilities of platelet-targeted interventions of T cell immunity.

Analysis of spatial-temporal distribution of notifiable respiratory infectious diseases in Shandong Province, China during 2005-2014.

BACKGROUND: Little comprehensive information on overall epidemic trend of notifiable respiratory infectious diseases is available in Shandong Province, China. This study aimed to determine the spatiotemporal distribution and epidemic characteristics of notifiable respiratory infectious diseases. METHODS: Time series was firstly performed to describe the temporal distribution feature of notifiable respiratory infectious diseases during 2005-2014 in Shandong Province. GIS Natural Breaks (Jenks) was applied to divide the average annual incidence of notifiable respiratory infectious diseases into five grades. Spatial empirical Bayesian smoothed risk maps and excess risk maps were further used to investigate spatial patterns of notifiable respiratory infectious diseases. Global and local Moran's I statistics were used to measure the spatial autocorrelation. Spatial-temporal scanning was used to detect spatiotemporal clusters and identify high-risk locations. RESULTS: A total of 537,506 cases of notifiable respiratory infectious diseases were reported in Shandong Province during 2005-2014. The morbidity of notifiable respiratory infectious diseases had obvious seasonality with high morbidity in winter and spring. Local Moran's I analysis showed that there were 5, 23, 24, 4, 20, 8, 14, 10 and 7 high-risk counties determined for influenza A (H1N1), measles, tuberculosis, meningococcal meningitis, pertussis, scarlet fever, influenza, mumps and rubella, respectively. The spatial-temporal clustering analysis determined that the most likely cluster of influenza A (H1N1), measles, tuberculosis, meningococcal meningitis, pertussis, scarlet fever, influenza, mumps and rubella included 74, 66, 58, 56, 22, 64, 2, 75 and 56 counties, and the time frame was November 2009, March 2008, January 2007, February 2005, July 2007, December 2011, November 2009, June 2012 and May 2005, respectively. CONCLUSIONS: There were obvious spatiotemporal clusters of notifiable respiratory infectious diseases in Shandong during 2005-2014. More attention should be paid to the epidemiological and spatiotemporal characteristics of notifiable respiratory infectious diseases to establish new strategies for its control.

Grafting resulting in alleviating tomato plant oxidative damage caused by high levels of ofloxacin.

Antibiotic pollution has become a global problem threatening human health. Ofloxacin is one of the more widely used antibiotics, but reports on the reaction of plant to ofloxacin pollution are limited. In this study, using adversity-resistant (R), adversity-sensitive (S) and grafted plant S/R as models, we investigated the biological response of tomato to exogenous ofloxacin residues. The results showed that lower levels of ofloxacin treatment (5 mg L-1 and 10 mg L-1) promoted tomato growth, and 10 mg L-1 ofloxacin was the critical dose to stimulate growth among the different treatments. In addition, the photosynthetic and fluorescence parameters, antioxidant enzyme activities and transcription-level expression of the enzymes were stimulated by low ofloxacin treatment. However, high ofloxacin treatment (20 mg L-1 and 40 mg L-1) exhibited a significantly negative effect on plant growth, photosynthesis, fluorescence parameters, antioxidant enzyme activities and transcript levels expression. Reactive oxygen species (ROS) and malondialdehyde (MDA) levels increased with increasing ofloxacin concentrations, indicating that the oxidative damage of plants was severe with increasing doses. In contrast, the role of antioxidant enzymes in the antibiotic response was limited at high ofloxacin concentrations. The grafting experiment demonstrated that grafted plants had the ability to alleviate ofloxacin stress. In conclusion, ofloxacin can damage the photosynthetic machinery by promoting ROS accumulation, which results in the etiolation of tomato leaves and inhibits plant growth, but grafting can reduce its.

The association between extreme temperature and pulmonary tuberculosis in Shandong Province, China, 2005-2016: a mixed method evaluation.

BACKGROUND: The effects of extreme temperature on infectious diseases are complex and far-reaching. There are few studies to access the relationship of pulmonary tuberculosis (PTB) with extreme temperature. The study aimed to identify whether there was association between extreme temperature and the reported morbidity of PTB in Shandong Province, China, from 2005 to 2016. METHODS: A generalized additive model (GAM) was firstly conducted to evaluate the relationship between daily reported incidence rate of PTB and extreme temperature events in the prefecture-level cities. Then, the effect estimates were pooled using meta-analysis at the provincial level. The fixed-effect model or random-effect model was selected based on the result of heterogeneity test. RESULTS: Among the 446,016 PTB reported cases, the majority of reported cases occurred in spring. The higher reported incidence rate areas were located in Liaocheng, Taian, Linyi and Heze. Extreme low temperature had an impact on the reported incidence of PTB in only one prefecture-level city, i.e., Binzhou (RR = 0.903, 95% CI: 0.817-0.999). While, extreme high temperature was found to have a positive effect on reported morbidity of PTB in Binzhou (RR = 0.924, 95% CI: 0.856-0.997) and Weihai (RR = 0.910, 95% CI: 0.843-0.982). Meta-analysis showed that extreme high temperature was associated with a decreased risk of PTB (RR = 0.982, 95% CI: 0.966-0.998). However, extreme low temperature was no relationship with the reported incidence of PTB. CONCLUSION: Our findings are suggested that extreme high temperature has significantly decreased the risk of PTB at the provincial levels. The findings have implications for developing strategies to response to climate change.

The Spectral Irradiance, Growth, Photosynthetic Characteristics, Antioxidant System, and Nutritional Status of Green Onion (Allium fistulosum L.) Grown Under Different Photo-Selective Nets.

The active regulation of the plant growth environment is a common method for optimizing plant yield and quality. In horticulture today, light quality control is carried out using photo-selective nets or membranes to improve the yield and quality of cultivated plants. In the present study, with natural light as the control (CK), we tested different photo-selective nets (white, WN; blue, BN; green, GN; yellow, YN; and red, RN) with 30% shade for characteristics of growth, development, quality, yield, photosynthesis, and chlorophyll fluorescence, considering the antioxidant system, as well as the influence of element absorption and transformation of green onion (Allium fistulosum L.) plants at different growth stages. We found that plants under BN and WN have greater height and fresh weight than those of plants under the other nets. Plants under the BN treatment had the highest quality, yield, photosynthetic pigment content, net photosynthetic rate, transpiration rate, and stomatal conductance, whereas the intercellular CO2 concentration was the highest in plants in the YN treatment. The photosynthesis noon break phenomenon was significantly lower in plants with covered photo-selective nets than in CK plants. NPQ was the highest in the YN treatment, and Fv/Fm, ΦPSII, and qP among the plants in the other treatments were different; from highest to lowest, they were as follows: BN > WN > CK > RN > GN > YN. The active oxygen content of green onion leaves in the BN treatment was significantly lower than that in the other treatments, and their key enzyme activity was significantly increased. BN also improved the absorption and transformation of elements in various organs of green onion.

Response of growth, photosynthetic electron transfer, and chloroplast ultrastructure to different LED light combination in green onion (Allium fistulosum L.).

With the rapid development of facility agriculture, it has become popular to study the influences of different light qualities on the growth, material metabolism, and morphology of horticultural crops. Last several years, green onions cultivation models have undergone major changes, and facility cultivation has developed rapidly. To determine the impact of light quality on the green onions, we studied the parameters connected to photosynthesis, incorporating growth, and development, photosynthetic rate (Pn ), chlorophyll fluorescence, light response curve, photosynthetic electron transfer, and chloroplast ultrastructure. We roundly analyzed the influences of different LED light combination (white: W, white-blue combination 3:1:WB, white-green combination 3:1:WG, white-yellow combination 3:1:WY, and white-red combination 3:1:WR, light intensity: 500 ± 10 µmol photons m-2 s-1 ) on the photosynthetic performance of green onions. The WB light led to better results than those of the WR, WG, and WY. There were significant performance improvements in leaf area, plant height, stem thickness, relative growth rate (RGR), pigment content, photosynthetic capacity, photosynthetic electron transfer efficiency, and chloroplast ultrastructure integrity. In contrast, plants treated with WG and WY were exposed to appreciably blocked light, but they effectively formed a light protection mechanism. The results of this research not only provided insight into the response mechanism of crop photosynthesis to different light qualities, but they also provided a scientific foundation for better planting green onions.

Over-expression of Fgf8 in cardiac neural crest cells leads to persistent truncus arteriosus.

During cardiogenesis, the outflow tract undergoes a complicated morphogenesis, including the re-alignment of the great blood vessels, and the separation of aorta and pulmonary trunk. The deficiency of FGF8 in the morphogenesis of outflow tract has been well studied, however, the effect of over-dosed FGF8 on the development of outflow tract remains unknown. In this study, Rosa26R-Fgf8 knock-in allele was constitutively activated by Wnt1-cre transgene in the mouse neural crest cells presumptive for the endocardial cushion of outflow tract. Surprisingly, Wnt1-cre; Rosa26R-Fgf8 mouse embryos exhibited persistent truncus arteriosus and died prior to E15.5. The cardiac neural crest cells in Wnt1-cre; Rosa26R-Fgf8 truncus arteriosus did not degenerate as in WT controls, but proliferated into a thickened endocardial cushion and then, blocked the blood outflow from cardiac chambers into the lungs, which resulted in the embryonic lethality. Although the spiral aorticopulmonary septum failed to form, the differentiaion of the endothelium and smooth muscle in the Wnt1-cre; Rosa26R-Fgf8 truncus arteriosus were impacted little. However, lineage tracing assay showed that the neural crest derived cells aggregated in the cushion layer, but failed to differentiate into the endothelium of Wnt1-cre; Rosa26R-Fgf8 truncus arteriosus. Further investigation displayed the reduced p-Akt and p-Erk immunostaining, and the decreased Bmp2 and Bmp4 transcription in the endothelium of Wnt1-cre; Rosa26R-Fgf8 truncus arteriosus. Our findings suggested that Fgf8 over-expression in cardiac neural crest impaired the formation of aorticopulmonary septum by suppressing the endothelial differentiation and stimulating the proliferation of endocardial cushion cells, which implicated a novel etiology of persistent truncus arteriosus.

Comparison of the effects of LED light quality combination on growth and nutrient accumulation in green onion (Allium fistulosum L.).

The growth and development and metabolism of plants have different physiological responses to different light qualities. To study the influence of light qualities on green onions, the impacts of LED light treatment on the growth and development as well as the nutritional components and flavor substances in green onions were studied under controlled conditions. Leaf area, plant height, dry matter accumulation, Dickson's quality index (DQI), nutritional content, and volatile compounds under different light quality treatments were determined. The results indicated that the white and blue combined light (W/B: 3/1) treatment was the most beneficial to growth and nutrient accumulation and led to higher levels of sulfur compounds in the green onions than the other treatments. This shows that it is possible to control the contents of compounds that affect consumer preferences by adjusting the lighting conditions and to thereby increase the value and quality of seasoning vegetables.

Ofloxacin induces etiolation in Welsh onion leaves.

Antibiotic pollution has become an important global issue, and ofloxacin (OFL) is widely used worldwide. However, little is known about the potential adverse effects of OFL on plants. We assessed the toxic effects of OFL on Welsh onion and explored its toxicity mechanism. The leaf pigment content increased in 0.1 mg/L of OFL but decreased in a dose-dependent manner (0.5-2 mg/L OFL) until leaf etiolation. The ultrastructure of leaves showed that the treatment of 2 mg/L OFL produced significant toxicity. Furthermore, photosynthetic and fluorescence parameters were negatively affected by OFL treatment. The photosynthetic electron transport chain was significantly inhibited by OFL treatment, especially between QA and QB. The hydrogen peroxide and malondialdehyde content also increased with OFL concentration, indicating that antioxidant enzymes' role in antibiotic response is limited. In conclusion, OFL can damage chloroplasts by promoting ROS accumulation, which results in the etiolation of Welsh onion leaves.

Effects of Floods on the Incidence of Acute Hemorrhagic Conjunctivitis in Mengshan, China, from 2005 to 2012.

This study aimed to examine the association between floods and the morbidity of acute hemorrhagic conjunctivitis (AHC) in Mengshan, China. Relying on the longitudinal data, a generalized additive model (GAM) was applied to quantify the relationship between the morbidity of AHC and floods from 2005 to 2012, controlling for other meteorological variables. Years lived with disability (YLDs) and attributable YLDs were used as the measure of the burden of AHC because of the floods. Multivariable analysis showed that floods were significantly associated with an increased risk of the morbidity of AHC (rate ratio [RR] = 2.136, 95% CI: 2.109-2.163). The total YLDs per 1,000 in Mengshan was 0.2001, although the value in females was higher than that in males (0.2351 versus 0.1686). The YLD per 1,000 of AHC in Mengshan was highest between the ages of 5 and 14 years (0.6530), followed by the age of 0-4 years (0.3325). The attributable YLD per 1,000 of AHC due to the floods in Mengshan was 0.0434 (95% CI: 0.0425-0.0442). Our study confirms that floods have significantly increased the risks of AHC in the selected study area. Females and youngsters may be the vulnerable populations to develop the flood-related disease.

Photosynthetic characteristics and chloroplast ultrastructure of welsh onion (Allium fistulosum L.) grown under different LED wavelengths.

BACKGROUND: The optimized illumination of plants using light-emitting diodes (LEDs) is beneficial to their photosynthetic performance, and in recent years, LEDs have been widely used in horticultural facilities. However, there are significant differences in the responses of different crops to different wavelengths of light. Thus, the influence of artificial light on photosynthesis requires further investigation to provide theoretical guidelines for the light environments used in industrial crop production. In this study, we tested the effects of different LEDs (white, W; blue, B; green, G; yellow, Y; and red, R) with the same photon flux density (300 µmol/m2·s) on the growth, development, photosynthesis, chlorophyll fluorescence characteristics, leaf structure, and chloroplast ultrastructure of Welsh onion (Allium fistulosum L.) plants. RESULTS: Plants in the W and B treatments had significantly higher height, leaf area, and fresh weight than those in the other treatments. The photosynthetic pigment content and net photosynthetic rate (Pn) in the W treatment were significantly higher than those in the monochromatic light treatments, the transpiration rate (E) and stomatal conductance (Gs) were the highest in the B treatment, and the intercellular CO2 concentration (Ci) was the highest in the Y treatment. The non-photochemical quenching coefficient (NPQ) was the highest in the Y treatment, but the other chlorophyll fluorescence characteristics differed among treatments in the following order: W > B > R > G > Y. This includes the maximum photochemical efficiency of photosystem II (PSII) under dark adaptation (Fv/Fm), maximum photochemical efficiency of PSII under light adaptation (Fv'/Fm'), photochemical quenching coefficient (qP), actual photochemical efficiency (ΦPSII), and apparent electron transport rate (ETR). Finally, the leaf structure and chloroplast ultrastructure showed the most complete development in the B treatment. CONCLUSIONS: White and blue light significantly improved the photosynthetic efficiency of Welsh onions, whereas yellow light reduced the photosynthetic efficiency.

Low pH altered salt stress in antioxidant metabolism and nitrogen assimilation in ginger (Zingiber officinale) seedlings.

The effects of low pH on antioxidant metabolism and nitrogen (N) assimilation in ginger seedlings under salt stress were investigated. A two-way randomized block design was used: the main treatment consisted of two pH levels, normal and low pH (6.0 and 4.0, respectively), and the other treatment consisted of two salinity levels, 0 and 100 mmol l-1 Na+ (NaCl and Na2 SO4 ). The results showed that low pH decreased the malondialdehyde (MDA) and hydrogen peroxide contents of ginger seedling leaves under salt stress. Moreover, low pH and salt stress significantly decreased the contents of non-enzymatic antioxidants, including ascorbate (AsA) and glutathione (GSH), and increased the activities of antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR) and glutathione reductase (GR). In addition, salt stress inhibited the N assimilation process in ginger seedling leaves, but low pH improved N assimilation under salt stress. Our finding was that low pH alleviated oxidative damage and promoted N assimilation under salt stress.

Comparative analysis of the chemical composition and water permeability of the cuticular wax barrier in Welsh onion (Allium fistulosum L.).

Cuticular wax is a hydrophobic barrier between the plant surface and the environment that effectively reduces the loss of water. The surface of Welsh onion leaves is covered with wax. To explain the relationship between wax composition and water loss, we conducted this experiment. The water permeability and wax composition of leaves were determined by chemical and GC-MS methods. We performed a comparative analysis of the differences between the two cultivars and analyzed the relationship between water permeability and waxy components. Overall, the permeability to water was higher in 'Zhangqiu' than in 'Tenko'. The wax amount of 'Tenko' was 1.28-fold higher than that of 'Zhangqiu' and was primarily explained by the much larger amounts of ketones and alcohols in the former. Among the waxy components, C29 ketones were most abundant. There were substantial discrepancies in wax composition, total wax content, and water permeability between the two cultivars. The main reason for the discrepancy in water permeability may be the significantly lower aliphatic fraction in 'Zhangqiu' than in 'Tenko'. This study makes a vital contribution to drought resistance research on allium plants.

A time-trend ecological study for identifying flood-sensitive infectious diseases in Guangxi, China from 2005 to 2012.

BACKGROUND: Flood-related damage can be very severe and include health effects. Among those health impacts, infectious diseases still represent a significant public health problem in China. However, there have been few studies on the identification of the spectrum of infectious diseases associated with floods in one area. This study aimed to quantitatively identify sensitive infectious diseases associated with floods in Guangxi, China. METHODS: A time-trend ecological design was conducted. A descriptive analysis was first performed to exclude infectious diseases with low incidence from 2005 to 2012 in ten study sites of Guangxi. The Wilcoxon rank-sum test was applied to examine the difference in the ten-day attack rate of infectious diseases between the exposure and control periods with different lagged effects. Negative binomial, zero-inflated Poisson and zero-inflated negative binomial models were used to examine the relationship and odd ratios (ORs) of the risk of floods on infectious diseases of preliminary screening. RESULTS: A total of 417,271 infectious diseases were notified. There were 11 infectious diseases associated with floods in the preliminary screening process for flood-sensitive infectious diseases. The strongest effect was shown with a 0-9 ten-day lag in different infectious diseases. Multivariate analysis showed that floods were significantly associated with an increased the risk of bacillary dysentery (odds ratio (OR) = 1.268, 95% confidence interval (CI): 1.072-1.500), acute haemorrhagic conjunctivitis (AHC, OR = 3.230, 95% CI: 1.976-5.280), influenza A (H1N1) (OR = 1.808, 95% CI: 1.721-1.901), tuberculosis (OR = 1.200, 95% CI: 1.036-1.391), influenza (OR = 2.614, 95% CI: 1.476-4.629), Japanese encephalitis (OR = 2.334, 95% CI: 1.119-4.865), and leptospirosis (OR = 1.138, 95% CI: 1.075-1.205), respectively. CONCLUSION: The spectrum of infectious diseases which are associated with floods are bacillary dysentery, AHC, influenza A (H1N1), tuberculosis, influenza, Japanese encephalitis and leptospirosis in Guangxi. Floods can result in differently increased risk of these diseases, and public health action should be taken to control a potential risk of these diseases after floods.

Effect of recombinant human thrombopoietin on immune thrombocytopenia in pregnancy in a murine model.

Primary immune thrombocytopenia (ITP) is a serious medical disorder that has the potential for maternal and fetal mortality. Corticosteroids, intravenous immunoglobulin, or both are the first-line treatments for ITP in pregnancy, but choices are limited if patients fail to respond. Recombinant human thrombopoietin (rhTPO) has been proved effective and safe in management of chronic ITP. However, the efficacy and safety of rhTPO for pregnant ITP patients still need to be explored. Here we developed an ideal murine model that simulated human ITP in pregnancy and evaluated the efficacy and safety of rhTPO in management of ITP in pregnancy. Model mice were subcutaneously administered with 0, 150, 1,500 and 15,000 U/kg rhTPO for 14 days. Significant higher platelet counts were noted in rhTPO-treated groups on Day 7, 10 and 14. On Day 20, half the maternal mice were sacrificed. Frequencies of Tregs in CD4+ T cells in rhTPO-treated groups were statistically higher than control. Significant higher plasma levels of TGF-ß1 were observed in rhTPO-treated groups than control. There was no significant abnormality in gross or visceral examination of fetuses. The remaining half maternal mice and their pups were observed for at least three weeks to assess vital signs. No abnormal signs were noted. Furthermore, we investigated the underlying mechanisms. Results showed that Tregs were negative for c-Mpl and rhTPO had no direct effect on Tregs. Additionally, the Treg frequency in splenic CD4+ T cells in LY2109761-treated model mice was statistically lower than control. Thus, rhTPO may be a safe and effective option for treatment of pregnant ITP patients.

Reproductive and developmental toxicity study of caffeic acid in mice.

Caffeic acid is an antioxidant commonly used to promote hematopoiesis and hemostasis. However, little is known about its systemic safety profile in reproduction and development. Here, we focused on the reproductive and developmental toxicity of caffeic acid in F0 female mice and F1 offspring. In the three-segment study, the F0 female mice were continuously exposed to 0, 0.15, 5 or 150 mg/kg/day of caffeic acid by gavage. We found that 5 mg/kg/day and 150 mg/kg/day of caffeic acid affected implantation of embryos when administered before gestation day 6. In addition, 150 mg/kg/day of caffeic acid affected fetal weight gain. No maternal toxicity, fetal teratogenesis or post-natal effects on pup development were observed. The no-observed-adverse-effect-level was 0.15 mg/kg/day for pregnant mice under the conditions of this study.

Inactivation of Fam20b in the neural crest-derived mesenchyme of mouse causes multiple craniofacial defects.

The glycosaminoglycan (GAG) chains attached to the core proteins of proteoglycans exert multiple roles, such as enriching signal molecules and regulating the binding of ligands to the corresponding receptors. A newly identified kinase - family with sequence similarity 20 member B (FAM20B) - is essential for the formation of GAG chains. The FAM20B protein phosphorylates the initial xylose on the side chain of a serine residue in the protein. Although the GAG chains of proteoglycans are believed to be indispensable during craniofacial development, there are few reports on their exact functions in craniofacial organogenesis. In this study, by mating Wnt1-cre mice with Fam20b-floxed mice (Fam20bflox/flox), we created Wnt1-Cre;Fam20bflox/flox mice in which Fam20b is ablated in the neural crest-derived mesenchyme. The Wnt1-Cre;Fam20bflox/flox mice died immediately after birth because of complete cleft palates. In addition to cleft palate, Wnt1-Cre;Fam20bflox/flox mice also manifested tongue elevation, micrognathia, microcephaly, suture widening, and reduced mineralization in the calvaria, facial bones, and temporomandibular joint. These findings indicate that the proteoglycans formed through the catalysis of FAM20B are essential for the morphogenesis and mineralization of the craniofacial complex.

Association between floods and infectious diarrhea and their effect modifiers in Hunan province, China: A two-stage model.

BACKGROUND: Understanding the potential links between floods and infectious diarrhea is important under the context of climate change. However, little is known about the risk of infectious diarrhea after floods and what factors could modify these effects in China. OBJECTIVES: This study aims to quantitatively examine the relationship between floods and infectious diarrhea and their effect modifiers. METHODS: Weekly number of infectious diarrhea cases from 2004 to 2011 during flood season in Hunan province were supplied by the National Notifiable Disease Surveillance System. Flood and meteorological data over the same period were obtained. A two-stage model was used to estimate a provincial average association and their effect modifiers between floods and infectious diarrhea, accounting for other confounders. RESULTS: A total of 134,571 cases of infectious diarrhea were notified from 2004 to 2011. After controlling for seasonality, long-term trends, and meteorological factors, floods were significantly associated with infectious diarrhea in the provincial level with a cumulative RR of 1.22 (95% CI: 1.05, 1.43) with a lagged effect of 0-1 week. Geographic locations and economic levels were identified as effect modifiers, with a higher impact of floods on infectious diarrhea in the western and regions with a low economic level of Hunan. CONCLUSIONS: Our study provides strong evidence of a positive association between floods and infectious diarrhea in the study area. Local control strategies for public health should be taken in time to prevent and reduce the risk of infectious diarrhea after floods, especially for the vulnerable regions identified.