[Estimation of soil moisture and organic matter content in saline alkali farmland by using CARS algorithm combined with covariates]. / 利用CARS算法联合协变量估算盐碱农田土壤水分和有机质含量.

Rapid acquisition of the data of soil moisture content (SMC) and soil organic matter (SOM) content is crucial for the improvement and utilization of saline alkali farmland soil. Based on field measurements of hyperspectral reflectance and soil properties of farmland soil in the Hetao Plain, we used a competitive adaptive reweighted sampling algorithm (CARS) to screen sensitive bands after transforming the original spectral reflectance (Ref) into a standard normal variable (SNV). Strategies Ⅰ, Ⅱ, and Ⅲ were used to model the input variables of Ref, Ref SNV, Ref-SNV+ soil covariate (SC), and digital elevation model (DEM). We constructed SMC and SOM estimation models based on random forest (RF) and light gradient boosting machine (LightGBM), and then verified and compared the accuracy of the models. The results showed that after CARS screening, the sensitive bands of SMC and SOM were compressed to below 3.3% of the entire band, which effectively optimized band selection and reduced redundant spectral information. Compared with the LightGBM model, the RF model had higher accuracy in SMC and SOM estimation, and the input variable strategy Ⅲ was better than Ⅱ and Ⅰ. The introduction of auxiliary variables effectively improved the estimation ability of the model. Based on comprehensive analysis, the coefficient of determination (Rp2), root mean square error (RMSE), and relative analysis error (RPD) of the SMC estimation model validation based on strategy Ⅲ-RF were 0.63, 3.16, and 2.01, respectively. The SOM estimation models based on strategy Ⅲ-RF had Rp2, RMSE, and RPD of 0.93, 1.15, and 3.52, respectively. The strategy Ⅲ-RF model was an effective method for estimating SMC and SOM. Our results could provide a new method for the rapid estimation of soil moisture and organic matter content in saline alkali farmland.

Inversion of soil water and salt information based on UAV hyperspectral remote sensing and machine lear-ning.

Accurate diagnosis of water and salt information in saline agricultural lands is crucial for long-term soil quality improvement and arable land conservation. In this study, we extracted field-scale vegetation canopy spectral information by UAV hyperspectral information, transforming the reflectance (R) to standard normal variate transformation (SNV), multiplicative scatter correction (MSC), first derivative of reflectance (FDR) and second derivative of reflectance (SDR). We determined the optimal spectral transformation forms of soil water content (SWC), soil pH, and soil salt content (SSC) by the maximum absolute correlation coefficient (MACC), and extracted the feature bands by competitive adaptive reweighted sampling (CARS). We constructed an inversion model of soil water and salt information by partial least squares regression (PLSR), random forest (RF), and extreme gradient boosting (XGBoost). The results showed that R, FDR and MSC were the best spectral transformation types for soil water content, soil pH, and soil salt content, and the corresponding MACC were 0.730, 0.472 and 0.654, respectively. The CARS algorithm effectively eliminated the irrelevant variables, optimally selecting 16-17 feature bands from 150 spectral bands. Both soil water content and soil pH performed best with XGBoost model, achieving determination coefficient of validation (Rp2) 0.927 and 0.743, and the relative percentage difference (RPD) amounted to 3.93 and 2.45. For soil salt content, the RF model emerged as the best inversion method with Rp2 and RPD of 0.427 and 1.64, respectively. The study could provide a reference solution for the integrated remote sensing monitoring of soil water and salt information in space and sky, serving as a scientific guide for the amelioration and sustainable management of saline lands.

Hyperspectral inversion of soil water and salt information based on fractional order derivative technology.

Accurate and efficient acquisition of soil water and salt information is a prerequisite for the improvement and sustainable utilization of saline lands. With the ground field hyperspectral reflectance and the measured soil water-salt content as data sources, we used the fractional order differentiation (FOD) technique to process hyperspectral data (with a step length of 0.25). The optimal FOD order was explored at the correlation level of spectral data and soil water-salt information. We constructed two-dimensional spectral index, support vector machine regression (SVR) and geographically weighted regression (GWR). The inverse model of soil water-salt content was finally evaluated. The results showed that FOD technique could reduce the hyperspectral noise and explore the potential spectral information to a certain extent, improve the correlation between spectrum and characteristics, with the highest correlation coefficients of 0.98, 1.35 and 0.33. The combination of characteristic bands screened by FOD and two-dimensional spectral index were more sensitive to characteristics than one-dimensional bands, with the optimal responses of order 1.5, 1.0 and 0.75. The optimal combinations of bands for maximum absolute correction coefficient of SMC were 570, 1000, 1010, 1020, 1330 and 2140 nm, pH were 550, 1000, 1380 and 2180 nm, and salt content were 600, 990, 1600 and 1710 nm, respectively. Compared with the original spectral reflectance, the validation coefficients of determination (Rp2) of the optimal order estimation models for SMC, pH, and salinity were improved by 1.87, 0.94 and 0.56, respectively. The overall GWR accuracy in the proposed model was better than SVR, where the GWR optimal order estimation models Rp2 were 0.866, 0.904 and 0.647, and the relative per-centage difference were 3.54, 4.25 and 1.86, respectively. The overall spatial distribution of soil water and salt content in the study area was characterized by low in the west and high in the east, with more serious soil alkalinization problems in the northwest and less severe in the northeast. The results would provide scientific basis for the hyperspectral inversion of soil water and salt in the Yellow River Irrigation Area and a new strategy for the implementation and management of precision agriculture in saline soil areas.

Estimation of soil organic matter content in Yinchuan Plain based on fractional derivative combined with spectral indices.

Soil organic matter (SOM) is a crucial indicator of soil fertility. Field hyperspectral reflectance and laboratory SOM data of soil samples from the Yinchuan Plain were used to explore the performance of models based on fractional derivative combined with different spectral indices. Following reciprocal and logarithmic transformation, the reflectance data were processed using fractional derivative from 0 to 2 orders (interval 0.20). Then, the difference index (DI), ratio index (RI), brightness index (BI), normalized difference index (NDI), renormalized difference index (RDI), and generalized difference index (GDI) were constructed. The two-dimensional correlation between the six indices and SOM content were analyzed. The optimal spectral indices were selected to establish SOM estimation models with principal component regression (PCR), partial least square regression (PLSR), back propagation neural network (BPNN), support vector machine (SVM), and geographically weighted regression (GWR). Results showed that the maximum absolute correlation coefficient (MACC) values between DI, RI, NDI, BI, GDI, RDI, and SOM contents increased firstly and then decreased, with the highest values observed at 1.0, 0.6, 1.4, and 1.6 orders. The 0.2-2.0 order RDI under fractional derivative variation could be used for subsequent model construction, in which the optimal combinations of bands for MACC values were mainly concentrated at 400-600 nm and 1300-1700 nm. Among the different models based on the single spectral index RDI, the model based on SVM achieved the highest estimation accuracy, whose modeling determination coefficient, verification determination coefficient and relative percentage difference reached 0.86, 0.87 and 2.32. Our results would provide a scientific reference for quick and accurate SOM assessment and mapping in areas with relatively low SOM content.

Association of Nap Frequency With Hypertension or Ischemic Stroke Supported by Prospective Cohort Data and Mendelian Randomization in Predominantly Middle-Aged European Subjects.

BACKGROUND AND PURPOSE: The aim of this study was to investigate the association between daytime napping frequency and the incidence of essential hypertension or stroke as well as to validate causality in this relationship via Mendelian randomization (MR). METHODS: We conducted Cox regression analysis on 358 451 participants free of hypertension or stroke from UK Biobank. To validate the results of the observational analysis, we conducted a 2-sample MR for daytime napping frequency (123 single-nucleotide polymorphisms) with essential hypertension in FinnGen Biobank, stroke, and ischemic stroke in MEGASTROKE consortium and performed a corresponding 1-sample MR on the UK Biobank data. RESULTS: Compared with never napping, usually napping was associated with a higher risk of essential hypertension (hazard ratio, 1.12 [95% CI, 1.08-1.17]), stroke (hazard ratio, 1.24 [95% CI, 1.10-1.39], and ischemic stroke (hazard ratio, 1.20 [95% CI, 1.05-1.36]) in our prospective observational analysis. Both the 1-sample and 2-sample MR results indicated that increased daytime napping frequency was likely to be a potential causal risk factor for essential hypertension in FinnGEN (odds ratio, 1.43 [95% CI, 1.06-1.92]) and UK Biobank (odds ratio, 1.40 [95% CI, 1.28-1.58]). The 2-sample MR results supported the potential causal effect of nap frequency on ischemic stroke in MEGASTROKE (odds ratio, 1.29 [95% CI, 1.04-1.62]). CONCLUSIONS: Prospective observational and MR analyses provided evidence that increased daytime nap frequency may represent a potential causal risk factor for essential hypertension. The potential causal association of increased nap frequency with ischemic stroke was supported by 2-sample MR and prospective observational results.

[Effects of different spectra types on the accuracy and correction of soil salt content inversion in Yinchuan Plain, China]. / ä¸åŒå ‰è°±ç±»åž‹å¯¹é“¶å·å¹³åŽŸåœŸå£¤å«ç›é‡åæ¼”ç²¾åº¦çš„å½±å“ä¸Žæ ¡æ­£.

Soil salinization is one of key drivers for the degradation of soil quality and yield in arable land. To accurately and quickly evaluate soil salt content in Yinchuan Plain, field and indoor hyperspectral data were processed with first order differential (FDR) transformation, then the feature bands were identified by stepwise regression (SR). Partial least squares regression (PLSR) and support vector machines (SVM) were used to build models, which were verified to figure out the optimal hyperspectral type for the study area. Moreover, segmented and global corrections were performed to process poor hyperspectral, aiming to improve the accuracy of soil salt content inversion. The results showed that the accuracy of soil salt content inversion model based on field hyperspectral data was 58.9% higher than that of the indoor hyperspectral data. The accuracy of the inversion was improved through the segmented and global correction of the indoor hyperspectral. We found that the segmented correction is more accurate for the PLSR model (Rc2=0.790, Rp2=0.633, RPD=1.64) and the global correction is more accurate for the SVM model (Rc2=0.927, Rp2=0.947, RPD=3.87). The SVM models' inversion accuracy was higher than that of PLSR, with the field hyperspectral model fitted the best, followed by the indoor hyperspectral processed with the global correction and the indoor hyperspectral processed with the segmented correction, while the indoor hyperspectral the worst. Our results suggest that field hyperspectral data could contribute to the quantitative inversion of soil salt content in Yinchuan Plain. The corrected indoor hyperspectral could significantly enhance the inversion accuracy of soil salt content, which could guarantee food security and ecological quality development.

The quality of reporting of randomized controlled trials of HuatuoZaizao pill for stroke.

Background: HuatuoZaizao pill (HZP), a Chinese patent medicine, is often used in the treatment of stroke. However, there is still a lack of enough evidence to recommend the routine use of HZP for stroke. This study is aimed at evaluating the quality of reporting of randomized controlled trials (RCTs) on HZP for stroke. Methods: RCTs on HuatuoZaizao pill for stroke were evaluated by using Consolidated Standards of Reporting Trials (CONSORT) guidelines and CONSORT extension criteria on reporting herbal interventions (CONSORT-CHM) guidelines. Microsoft Excel 2007 and SPSS20.0 was used for statistics analyses. Results: Seventeen studies involving 1801 stroke patients were identified. CONSORT-CHM has expanded 24.3% (9/37) items in CONSORT and added a small item. The average scores of CONSORT evaluation is 14.6, while the average scores of the CONSORT-CHM evaluation is 11.6. The central items in CONSORT as eligibility criterion, sample size calculation, primary outcome, method of randomization sequence generation, allocation concealment, implementation of randomization, description of blinding, and detailed statistical methods were reported in 77%, 6%, 100%, 47%, 6%, 6%, 6%, and 94% of trials, respectively. In terms of the CONSORT-CHM, none of the articles reported in detail the dosage form, origin, formula basis and so on of HZP, and only half of studies reported the outcome indicators related to Traditional Chinese Medicine syndromes. Conclusion: The overall report quality of RCT related to HZP is low. HZP still needs to report higher quality RCTs to prove its effectiveness and safety.

Stem Cell-Based Therapy for Experimental Ischemic Stroke: A Preclinical Systematic Review.

Stem cell transplantation offers promise in the treatment of ischemic stroke. Here we utilized systematic review, meta-analysis, and meta-regression to study the biological effect of stem cell treatments in animal models of ischemic stroke. A total of 98 eligible publications were included by searching PubMed, EMBASE, and Web of Science from inception to August 1, 2020. There are about 141 comparisons, involving 5,200 animals, that examined the effect of stem cell transplantation on neurological function and infarct volume as primary outcome measures in animal models for stroke. Stem cell-based therapy can improve both neurological function (effect size, -3.37; 95% confidence interval, -3.83 to -2.90) and infarct volume (effect size, -11.37; 95% confidence interval, -12.89 to -9.85) compared with controls. These results suggest that stem cell therapy could improve neurological function deficits and infarct volume, exerting potential neuroprotective effect for experimental ischemic stroke, but further clinical studies are still needed.

PTP-MEG2 regulates quantal size and fusion pore opening through two distinct structural bases and substrates.

Tyrosine phosphorylation of secretion machinery proteins is a crucial regulatory mechanism for exocytosis. However, the participation of protein tyrosine phosphatases (PTPs) in different exocytosis stages has not been defined. Here we demonstrate that PTP-MEG2 controls multiple steps of catecholamine secretion. Biochemical and crystallographic analyses reveal key residues that govern the interaction between PTP-MEG2 and its substrate, a peptide containing the phosphorylated NSF-pY83 site, specify PTP-MEG2 substrate selectivity, and modulate the fusion of catecholamine-containing vesicles. Unexpectedly, delineation of PTP-MEG2 mutants along with the NSF binding interface reveals that PTP-MEG2 controls the fusion pore opening through NSF independent mechanisms. Utilizing bioinformatics search and biochemical and electrochemical screening approaches, we uncover that PTP-MEG2 regulates the opening and extension of the fusion pore by dephosphorylating the DYNAMIN2-pY125 and MUNC18-1-pY145 sites. Further structural and biochemical analyses confirmed the interaction of PTP-MEG2 with MUNC18-1-pY145 or DYNAMIN2-pY125 through a distinct structural basis compared with that of the NSF-pY83 site. Our studies thus provide mechanistic insights in complex exocytosis processes.

Generation of H11-albumin-rtTA Transgenic Mice: A Tool for Inducible Gene Expression in the Liver.

The modification of the mouse genome by site-specific gene insertion of transgenes and other genetic elements allows the study of gene function in different developmental stages and in the pathogenesis of diseases. Here, we generated a "genomic safe harbor" Hipp11 (H11) locus-specific knock-in transgenic mouse line in which the albumin promoter is used to drive the expression of the reverse tetracycline transactivator (rtTA) in the liver. The newly generated H11-albumin-rtTA transgenic mice were bred with tetracycline-operator-Histone-2B-green fluorescent protein (TetO-H2BGFP) mice to assess inducibility and tissue-specificity. Expression of the H2BGFP fusion protein was observed exclusively upon doxycycline (Dox) induction in the liver of H11-albumin-rtTA/TetO-H2BGFP double transgenic mice. To further analyze the ability of the Dox-inducible H11-albumin-rtTA mice to implement conditional DNA recombination, H11-albumin-rtTA transgenic mice were crossed with TetO-Cre and Ai14 mice to generate H11-albumin-rtTA/TetO-Cre/Ai14 triple transgenic mice. We successfully confirmed that the Cre-mediated recombination efficiency was as strong in Dox-induced H11-albumin-rtTA /TetO-Cre/Ai14 mice as in the control albumin-Cre/A14 mice. Finally, to characterize the expression-inducing effects of Dox in H11-albumin-rtTA/TetO-H2BGFP mice in detail, we examined GFP expression in embryos at different developmental stages and found that newly conceived H11-albumin-rtTA/TetO-H2BGFP embryos of Dox-treated pregnant female mice were expressing reporter GFP by E16.5. Our study demonstrates that these new H11-albumin-rtTA transgenic mice are a powerful and efficient tool for the temporally and spatially conditional manipulation of gene expression in the liver, and illustrates how genetic crosses with these new mice enable the generation of complex multi-locus transgenic animals for mechanistic studies.

Resveratrol enhances the functionality and improves the regeneration of mesenchymal stem cell aggregates.

Mesenchymal stem cell (MSC)-based regeneration, specifically cell aggregate or cell sheet engineering, is a promising approach for tissue reconstruction. Considering the advantages of ease of harvest and lack of immune rejection, the application of autologous MSCs (i.e., patients' own MSCs) in regenerative medicine has developed considerable interest. However, the impaired cell viability and regenerative potential following MSCs impacted by disease remain a major challenge. Resveratrol (RSV) exhibits reliable and extensive rejuvenative activities that have received increasing clinical attention. Here, we uncovered that resveratrol enhances the functionality and improves the regeneration of mesenchymal stem cell aggregates. Periodontal ligament MSCs (PDLSCs) from normal control subjects (N-PDLSCs) and periodontitis patients (P-PDLSCs) were investigated. Compared to N-PDLSCs, P-PDLSCs were less capable of forming cell aggregates, and P-PDLSC aggregates showed impaired osteogenesis and regeneration. These functional declines could be mimicked in N-PDLSCs by tumor necrosis factor alpha (TNF-α) treatment. Notably, a TNF-α-induced functional decline in N-PDLSC aggregates was rescued by RSV application. More importantly, in both N-PDLSCs and P-PDLSCs, RSV promoted cell aggregate formation and improved their osteogenic potential. Furthermore, as proven ectopically in vivo, the tissue regenerative capability of P-PDLSC aggregates was also enhanced after RSV treatment during aggregate formation in vitro. Finally, in a rat in situ regeneration model, we successfully applied both N-PDLSC aggregates and P-PDLSC aggregates to repair periodontal defects upon long-term functional improvements by RSV preconditioning. Together, our data unravel a novel methodology for using pharmacology (i.e., RSV)-based cell aggregate engineering to improve the functionality and facilitate the regeneration of MSCs from both healthy and inflammatory microenvironments, shedding light on improving the application of autologous MSC-mediated regenerative medicine.

Gq activity- and ß-arrestin-1 scaffolding-mediated ADGRG2/CFTR coupling are required for male fertility.

Luminal fluid reabsorption plays a fundamental role in male fertility. We demonstrated that the ubiquitous GPCR signaling proteins Gq and ß-arrestin-1 are essential for fluid reabsorption because they mediate coupling between an orphan receptor ADGRG2 (GPR64) and the ion channel CFTR. A reduction in protein level or deficiency of ADGRG2, Gq or ß-arrestin-1 in a mouse model led to an imbalance in pH homeostasis in the efferent ductules due to decreased constitutive CFTR currents. Efferent ductule dysfunction was rescued by the specific activation of another GPCR, AGTR2. Further mechanistic analysis revealed that ß-arrestin-1 acts as a scaffold for ADGRG2/CFTR complex formation in apical membranes, whereas specific residues of ADGRG2 confer coupling specificity for different G protein subtypes, this specificity is critical for male fertility. Therefore, manipulation of the signaling components of the ADGRG2-Gq/ß-arrestin-1/CFTR complex by small molecules may be an effective therapeutic strategy for male infertility.

Matrix Effects Originating from Coexisting Minerals and Accurate Determination of Stable Silver Isotopes in Silver Deposits.

Except for extensive studies in core formation and volatile-element depletion processes using radiogenic Ag isotopes (i.e., the Pd-Ag chronometer), recent research has revealed that the mass fractionation of silver isotopes is in principle controlled by physicochemical processes (e.g., evaporation, diffusion, chemical exchange, etc.) during magmatic emplacement and hydrothermal alteration. As these geologic processes only produce very minor variations of δ109Ag from -0.5 to +1.1‰, more accurate and precise measurements are required. In this work, a robust linear relationship between instrumental mass discrimination of Ag and Pd isotopes was obtained at the Ag/Pd molar ratio of 1:20. In Au-Ag ore deposits, silver minerals have complex paragenetic relationships with other minerals (e.g., chalcopyrite, sphalerite, galena, pyrite, etc.). It is difficult to remove such abundant impurities completely because the other metals are tens to thousands of times richer than silver. Both quantitative evaluation of matrix effects and modification of chemical chromatography were carried out to deal with the problems. Isobaric inferences (e.g., 65Cu40Ar+ to 105Pd, 208Pb2+ to 104Pd, and 67Zn40Ar+ to 107Ag+) and space charge effects dramatically shift the measured δ109Ag values. The selection of alternative Pd isotope pairs is effective in eliminating spectral matrix effects so as to ensure accurate analysis under the largest possible ranges for metal impurities, which are Cu/Ag ≤ 50:1, Fe/Ag ≤ 600:1, Pb/Ag ≤ 10:1, and Zn/Ag ≤ 1:1, respectively. With the modified procedure, we reported silver isotope compositions (δ109Ag) in geological standard materials and typical Au-Ag ore deposit samples varying from -0.029 to +0.689 ‰ with external reproducibility of ±0.009-0.084 ‰. A systemic survey of δ109Ag (or ε109Ag) variations in rocks, ore deposits, and environmental materials in nature is discussed.

Arrestin-biased AT1R agonism induces acute catecholamine secretion through TRPC3 coupling.

Acute hormone secretion triggered by G protein-coupled receptor (GPCR) activation underlies many fundamental physiological processes. GPCR signalling is negatively regulated by ß-arrestins, adaptor molecules that also activate different intracellular signalling pathways. Here we reveal that TRV120027, a ß-arrestin-1-biased agonist of the angiotensin II receptor type 1 (AT1R), stimulates acute catecholamine secretion through coupling with the transient receptor potential cation channel subfamily C 3 (TRPC3). We show that TRV120027 promotes the recruitment of TRPC3 or phosphoinositide-specific phospholipase C (PLCγ) to the AT1R-ß-arrestin-1 signalling complex. Replacing the C-terminal region of ß-arrestin-1 with its counterpart on ß-arrestin-2 or using a specific TAT-P1 peptide to block the interaction between ß-arrestin-1 and PLCγ abolishes TRV120027-induced TRPC3 activation. Taken together, our results show that the GPCR-arrestin complex initiates non-desensitized signalling at the plasma membrane by coupling with ion channels. This fast communication pathway might be a common mechanism of several cellular processes.

Adaptive Activation of a Stress Response Pathway Improves Learning and Memory Through Gs and ß-Arrestin-1-Regulated Lactate Metabolism.

BACKGROUND: Stress is a conserved physiological response in mammals. Whereas moderate stress strengthens memory to improve reactions to previously experienced difficult situations, too much stress is harmful. METHODS: We used specific ß-adrenergic agonists, as well as ß2-adrenergic receptor (ß2AR) and arrestin knockout models, to study the effects of adaptive ß2AR activation on cognitive function using Morris water maze and object recognition experiments. We used molecular and cell biological approaches to elucidate the signaling subnetworks. RESULTS: We observed that the duration of the adaptive ß2AR activation determines its consequences on learning and memory. Short-term formoterol treatment, for 3 to 5 days, improved cognitive function; however, prolonged ß2AR activation, for more than 6 days, produced harmful effects. We identified the activation of several signaling networks downstream of ß2AR, as well as an essential role for arrestin and lactate metabolism in promoting cognitive ability. Whereas Gs-protein kinase A-cyclic adenosine monophosphate response element binding protein signaling modulated monocarboxylate transporter 1 expression, ß-arrestin-1 controlled expression levels of monocarboxylate transporter 4 and lactate dehydrogenase A through the formation of a ß-arrestin-1/phospho-mitogen-activated protein kinase/hypoxia-inducible factor-1α ternary complex to upregulate lactate metabolism in astrocyte-derived U251 cells. Conversely, long-term treatment with formoterol led to the desensitization of ß2ARs, which was responsible for its decreased beneficial effects. CONCLUSIONS: Our results not only revealed that ß-arrestin-1 regulated lactate metabolism to contribute to ß2AR functions in improved memory formation, but also indicated that the appropriate management of one specific stress pathway, such as through the clinical drug formoterol, may exert beneficial effects on cognitive abilities.

Tong Luo Jiu Nao, a Chinese Medicine Formula, Reduces Inflammatory Stress in a Mouse Model of Alzheimer's Disease.

AIM: The aim of this study is to extend the molecular mechanism of Tong Luo Jiu Nao (TLJN) for Alzheimer's disease (AD), which is a modern Chinese formula that has been used to treat AD. METHODS: The senescence-accelerated mouse prone 8 strain (SAMP8) is one of the most appropriate models to study the mechanism that underlies AD. The levels of plasma amyloid ß (Aß) and the Aß deposits were measured using enzyme-linked immunosorbent assay and immunohistochemistry. Immunoblotting was used to observe the effect of TLJN on inflammatory mediator expression in an senescence-accelerated mouse model of AD. RESULTS: Our data showed that the TLJN-treated groups exhibited a reduction in plasma Aß levels and reduced Aß expression. Moreover, TLJN effectively attenuated Aß-induced activation of extracellular signal-regulated kinase and c-Jun N-terminal kinases and blocked changes in inflammatory mediator expression. CONCLUSION: These data suggest that TLJN might have protective effects and could potentially act to attenuate inflammatory stress in the pathogenesis of AD.

Transforming growth factor-ß signaling participates in the maintenance of the primordial follicle pool in the mouse ovary.

Physiologically, only a few primordial follicles are activated to enter the growing follicle pool each wave. Recent studies in knock-out mice show that early follicular activation depends on signaling from the tuberous sclerosis complex, the mammalian target of rapamycin complex 1 (mTORC1), phosphatase and tensin homolog deleted on chromosome 10, and phosphatidylinositol 3-kinase (PI3K) pathways. However, the manner in which these pathways are normally regulated, and whether or not TGF-ß acts on them are poorly understood. So, this study aims to identify whether or not TGF-ß acts on the process. Ovary organ culture experiments showed that the culture of 18.5 days post-coitus (dpc) ovaries with TGF-ß1 reduced the total population of oocytes and activated follicles, accelerated oocyte growth was observed in ovaries treated with TGF-ßR1 inhibitor 2-(5-chloro-2-fluorophenyl)pteridin-4-yl]pyridin-4-yl-amine (SD208) compared with control ovaries, the down-regulation of TGF-ßR1 gene expression also activated early primordial follicle oocyte growth. We further showed that there was dramatically more proliferation of granulosa cells in SD208-treated ovaries and less proliferation in TGF-ß1-treated ovaries. Western blot and morphological analyses indicated that TGF-ß signaling manipulated primordial follicle growth through tuberous sclerosis complex/mTORC1 signaling in oocytes, and the mTORC1-specific inhibitor rapamycin could partially reverse the stimulated effect of SD208 on the oocyte growth and decreased the numbers of growing follicles. In conclusion, our results suggest that TGF-ß signaling plays an important physiological role in the maintenance of the dormant pool of primordial follicles, which functions through activation of p70 S6 kinase 1 (S6K1)/ribosomal protein S6 (rpS6) signaling in mouse ovaries.

Central apelin-13 inhibits food intake via the CRF receptor in mice.

Apelin, the novel identified peptide, is the endogenous ligand for the APJ. Previous studies have reported the effect of apelin on food intake, however the action of acute central injected apelin on food intake in mice remains unknown. The present study was designed to investigate the mechanism as well as the effect of central apelin-13 on food intake in mice. During the dark period, the cumulative food intake was significantly decreased at 4h after the intracerebroventricular (i.c.v.) injection of 1 and 3µg/mouse apelin-13 and the period food intake was significantly reduced during 2-4h after treatment. In the fasted mice, the cumulative food intake was significantly decreased at 2 and 4h after injection of 3µg/mouse apelin-13. The cumulative water intake was significantly reduced by apelin-13 (3µg/mouse) at 4h after injection in freely feeding and fasted mice. However, during light period, apelin-13 had no influence on food and water intake in freely feeding mice. The APJ receptor antagonist apelin-13(F13A) (6µg/mouse) and the corticotrophin-releasing factor (CRF) receptor antagonist α-helical CRF(9-41) (3µg/mouse) could reverse the inhibitory effect on cumulative food intake/0-4h induced by apelin-13 (3µg/mouse) in freely feeding mice during the dark period, whereas the anorexic effect could not be antagonized by the arginie vasopressin (AVP) receptor antagonist deamino(CH(2))(5)Tyr(Me)AVP (0.5µg/mouse). Taken together, these results suggest that central apelin-13 inhibits food intake in mice and it seems that APJ receptor and CRF receptor, but not AVP receptor, might be involved in this process.

[The tk gene mutation analysis in WTK1 cell line by multiplex PCR].

OBJECTIVE: To explore the tk gene mutation spectrum in spontaneous and induced WTK1 mutants. METHODS: After exposure to methyl methanesulfonate (MMS), mitomycin (MMC) or sodiam azide (NaN3), spontaneously-arising and induced mutants of WTK1 cell line were selected. The spectrum and hotspot of tk gene mutation were analyzed by multiplex PCR. RESULTS: Three chemicals used in this study induced tk mutation frequency (MF) to increase significantly in a dose-dependent manner; most of the analyzed mutants had lost exon 4 and exon 5-7. CONCLUSION: Three chemicals have mutagenic effect on WTK1 cell line, and obvious hotspot exists in tk gene mutation.

[Evaluation of the genotoxicity of vincristine and colchicine using mouse lymphoma tk mutation assay].

OBJECTIVE: To evaluate the genotoxicity of two mitotic inhibitors vincristine and colchicine, and to compare the detecting sensitivity of tk gene mutation assay with short-and long-term treatment by them. METHODS: Tk gene mutation assay was performed by microwell method with L5178Y mouse lymphoma cell line after exposing to vincristine and colchicine for 3 h and 24 h respectively, and the results of two different treating time were compared. RESULTS: The two chemicals didn't show positive responses in mouse lymphoma assay (MLA) with 3h treatment, but they could induce tk mutation frequency increase 1.6 to 4.8 and 2.1 to 6.2 times higher to spontaneous MF respectively after continuous treatment for 24 h. CONCLUSION: Vincristine and colchicine had mutagenic effect on tk gene with long-term treatment, which indicated that the detecting sensitivity of MLA could be enhanced by long-term treatment.