UCP1 and AOX1a contribute to regulation of carbon and nitrogen metabolism and yield in Arabidopsis under low nitrogen stress.

Nitrogen (N) availability is a critical factor for plant development and crop yield, and it closely correlates to carbon (C) metabolism. Uncoupling protein (UCP) and alternative oxidase (AOX) exhibit a strong correlation with N and C metabolism. Here, we investigated the functions of UCP1 and AOX1a using their mutants and complementation lines in Arabidopsis adaptation to low N. Low N markedly increased AOX1a and UCP1 expression, alternative pathway capacity and UCP activity. Eight-day-old aox1a/ucp1 seedlings were more sensitive to low N than Col-0 and single mutants, exhibiting lower primary root length and higher anthocyanin accumulation. The net photosynthetic rate, electron transport rate, PSII actual photochemical efficiency, stomatal conductance and carboxylation efficiency were markedly decreased in ucp1 and aox1a/ucp1 compared to those in Col-0 and aox1a under low N stress; comparatively, chlorophyll content and non-photochemical quenching coefficient were the lowest and highest in aox1a/ucp1, respectively. Nitrate acquisition rate was accelerated in aox1a/ucp1, but its transport activity was decreased, which resulted in low nitrate content and nitrate reductase activity under low N condition. The C/N ratio in seeds, but not in leaves, is higher in aox1a/ucp1 than that in Col-0, aox1a and ucp1 under low N condition. RNA-seq analysis revealed that many genes involved in photosynthesis and C/N metabolism were markedly down-regulated in aox1a/ucp1 under low N stress. These results highlight the key roles of UCP1 and AOX1a in modulating photosynthetic capacity, C/N assimilation and distribution under low N stress.

An easy-to-operate web-based calculator for predicting the progression of chronic kidney disease.

BACKGROUND: This study aimed to establish and validate an easy-to-operate novel scoring system based on simple and readily available clinical indices for predicting the progression of chronic kidney disease (CKD). METHODS: We retrospectively evaluated 1045 eligible CKD patients from a publicly available database. Factors included in the model were determined by univariate and multiple Cox proportional hazard analyses based on the training set. RESULTS: Independent prognostic factors including etiology, hemoglobin level, creatinine level, proteinuria, and urinary protein/creatinine ratio were determined and contained in the model. The model showed good calibration and discrimination. The area under the curve (AUC) values generated to predict 1-, 2-, and 3-year progression-free survival in the training set were 0.947, 0.931, and 0.939, respectively. In the validation set, the model still revealed excellent calibration and discrimination, and the AUC values generated to predict 1-, 2-, and 3-year progression-free survival were 0.948, 0.933, and 0.915, respectively. In addition, decision curve analysis demonstrated that the model was clinically beneficial. Moreover, to visualize the prediction results, we established a web-based calculator ( https://ncutool.shinyapps.io/CKDprogression/ ). CONCLUSION: An easy-to-operate model based on five relevant factors was developed and validated as a conventional tool to assist doctors with clinical decision-making and personalized treatment.

Creation of multiple on-axis foci and ultra-long focal depth for SPPs.

We present the design of a plasmonic lens (PL) which is composed of pixelated nano-grooves on a gold film for the coupling and focusing of surface plasmon polaritons (SPPs) into multiple focal spots on the optical axis. The pixelated grooves are arranged along the y-axis and the x-position of each groove is optimized by the simulated annealing algorithm. PLs that implement two and three on-axis foci are presented and the designed structures have been validated with FDTD simulations. We also successfully constructed a long-focal-depth PL with a longitudinal FWHM of the focus that reached 25 plasmonic wavelengths, while its transverse field profile is maintained over 15 µm distance. The presented design method constitutes a new basis for plasmonic beam engineering, and the proposed particular SPP focal fields have potential applications in multiple imaging, particle manipulating, and plasmonic on-chip signal transmission.

Targeting the aryl hydrocarbon receptor with FICZ regulates IL-2 and immune infiltration to alleviate Hashimoto's thyroiditis in mice.

Hashimoto's thyroiditis (HT) is the most frequent autoimmune disorder. Growing work points to the involvement of aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor, in the regulation of immune homeostasis. However, the roles of AhR and its ligands in HT remains unclear. In this study, we leveraged public human database analyses to postulate that the AhR expression was predominantly in thyroid follicular cells, correlating significantly with the thyroid infiltration levels of multiple immune cells in HT patients. Using a thyroglobulin-induced HT mouse model and in vitro thyroid follicular epithelial cell cultures, we found a significant downregulation of AhR expression in thyrocytes both in vivo and in vitro. Conversely, activating AhR by FICZ, a natural AhR ligand, mitigated inflammation and apoptosis in thyrocytes in vitro and conferred protection against HT in mice. RNA sequencing (RNA-seq) of thyroid tissues indicated that AhR activation moderated HT-associated immune or inflammatory signatures. Further, immunoinfiltration analysis indicated that AhR activation regulated immune cell infiltration in the thyroid of HT mice, such as suppressing cytotoxic CD8+ T cell infiltration and promoting anti-inflammatory M2 macrophage polarization. Concomitantly, the expression levels of interleukin-2 (IL-2), a lymphokine that downregulates immune responses, were typically decreased in HT but restored upon AhR activation. In silico validation substantiated the binding interaction between AhR and IL-2. In conclusion, targeting the AhR with FICZ regulates IL-2 and immune infiltration to alleviate experimental HT, shedding new light on the therapeutic intervention of this prevalent disease.

Responses of photosynthetic properties and chloroplast ultrastructure of Bryum argenteum from a desert biological soil crust to elevated ultraviolet-B radiation.

Our understanding of plant responses to enhanced ultraviolet-B (UV-B) radiation has improved over recent decades. However, research on cryptogams is scarce and it remains controversial whether UV-B radiation causes changes in physiology related to photosynthesis. To investigate the effects of supplementary UV-B radiation on photosynthesis and chloroplast ultrastructure in Bryum argenteum Hedw., specimens were cultured for 10 days under four UV-B treatments (2.75, 3.08, 3.25 and 3.41 W m(-2) ), simulating depletion of 0% (control), 6%, 9% and 12% of stratospheric ozone at the latitude of Shapotou, a temperate desert area of northwest China. Analyses showed malondialdehyde content significantly increased, whereas chlorophyll (Chl) fluorescence parameters and Chl contents decreased with increased UV-B intensity. These results corresponded with changes in thylakoid protein complexes and chloroplast ultrastructure. Overall, enhanced UV-B radiation leads to significant decreases in photosynthetic function and serious destruction of the chloroplast ultrastructure of B. argenteum. The degree of negative influences increased with the intensity of UV-B radiation. These results may not only provide a potential mechanism for supplemental UV-B effects on photosynthesis of moss crust, but also establish a theoretical basis for further studies of adaptation and response mechanisms of desert ecosystems under future ozone depletion.

Vegetation richness, species identity and soil nutrients drive the shifts in soil bacterial communities during restoration process.

Soil bacteria play an essential role in functioning of ecosystems and maintaining of biogeochemical cycles. However, little is known about changes in the compositions and functional groups of soil bacterial communities during different restoration stages. The influences of aboveground vegetation and belowground soil properties on soil bacterial communities were also unclear during this process. Here we sequenced the soil bacterial communities in different stages of sand fixation. Sand fixation increased the diversity of the bacterial communities, among which the populations of Actinobacteria, Acidobacteria and Gemmatimonadetes changed significantly. The function prediction showed sand fixation increased Gram-positive and aerobic bacteria. Bacterial structure is significantly correlated with plant richness, coverage and biomass. In particular, we found species identity was an important determinant in structuring bacterial composition. Soil properties were all significantly correlated with soil bacterial community richness and diversity. Fusobacteria was strongly positively correlated with sand, Chloroflexi with total N and Gemmatimonadetes with SOM and total C. It suggested that soil nutrients (TC, TN and SOM) have large consequences for soil bacterial community dissimilarities. These results indicated that vegetation richness, especially species identity, together with improvement in soil nutrients, play key roles in driving the shifts in soil microbial community structure and function during restoration process.

Noninvasive DW-MRI metrics for staging hepatic fibrosis and grading inflammatory activity in patients with chronic hepatitis B.

PURPOSE: To assess the value of various diffusion parameters obtained from monoexponential, biexponential, and stretched-exponential diffusion-weighted imaging (DWI) models for staging hepatic fibrosis (HF) and grading inflammatory activity in patients with chronic hepatitis B (CHB). METHODS: 82 patients with CHB and 30 healthy volunteers underwent DWI with 13 b-values on a 3T MRI unit. The standard apparent diffusion coefficient (ADCst) was calculated using a monoexponential model. The true diffusion coefficient (Dt), pseudo-diffusion coefficient (Dp), and perfusion fraction (f) were calculated using a biexponential model. The distributed diffusion coefficient (DDC) and water-molecule diffusion heterogeneity index (α) were calculated using a stretched-exponential model. Receiver operating characteristic (ROC) curves were performed for diffusion parameters to compare the diagnosis performance. RESULTS: The distributions of hepatic fibrosis stages and the inflammatory activity grades (METAVIR scoring system) were as follows: F0, n = 1; F1, n = 16; F2, n = 31; F3, n = 19; and F4, n = 15. A0, n = 1; A1, n = 14; A2, n = 46; and A3, n = 21. ADCst, Dt and DDC values showed negative correlation with the fibrosis stage (r = - 0.418, - 0.717 and - 0.630, all P < 0.001) and the inflammatory activity grade (r = - 0.514, - 0.626 and - 0.550, all P < 0.001). The area under the ROC curve (AUC) of Dt (AUC = 0.854, 0.881) and DDC (AUC = 0.794, 0.834) were significantly higher than that of ADCst (AUC = 0.637, 0.717) in discriminating significant fibrosis (≥ F2) and advanced fibrosis (≥ F3) (all P < 0.05). Although Dt (AUC = 0.867, 0.836) and DDC (AUC = 0.810, 0.808) showed higher AUCs than ADCst (AUC = 0.767, 0.803), there was no significant difference in their ability in detecting inflammatory activity grade ≥ A2/A3 (P > 0.05). CONCLUSIONS: Dt and DDC are promising indicators and outperform ADCst for staging HF. While both Dt and DDC have similar diagnostic performance compared with ADCst for grading inflammatory activity.

Non-invasive assessment of hepatic fibrosis: comparison of MR elastography to transient elastography and intravoxel incoherent motion diffusion-weighted MRI.

OBJECTIVE: To compare the ability of MR elastography (MRE) with transient elastography (TE) and intravoxel incoherent motion (IVIM) diffusion-weighted MRI in staging hepatic fibrosis (HF). MATERIALS AND METHODS: 100 patients with chronic liver disease and 25 healthy volunteers underwent preoperative MRE, IVIM on a 3T MRI unit, and ultrasound-based TE. Liver stiffness measurement from MRE (LSM-MRE) and liver stiffness measurement from TE (LSM-TE) were measured; four diffusion parameters including the true diffusion coefficient (Dt), pseudo-diffusion coefficient, perfusion fraction (f), and apparent diffusion coefficient (ADC) were calculated. Receiver operating characteristic (ROC) curves were performed for significant parameters to compare the diagnosis performance for detecting HF. RESULTS: LSM-MRE and LSM-TE values showed positive correlation with the fibrosis stage (r = 0.910 and 0.813, P < 0.001). Dt, f, and ADC values showed negative correlation with the fibrosis stage (r = - 0.727, - 0.503, and - 0.601, all P < 0.001). The area under the ROC curve (AUC) of LSM-MRE (AUC = 0.965, 0.957, 0.983) was significantly higher than that of LSM-TE (AUC = 0.906, 0.913, 0.931) and Dt (AUC = 0.875, 0.879, 0.861) in discriminating significant HF (≥ F2), advanced HF (≥ F3), or cirrhosis (F4) (all P < 0.05). Although LSM-TE showed higher AUCs than Dt in detecting fibrosis stages, there were no significant differences between LSM-TE and Dt (P > 0.05) except for detecting F4 (P < 0.05). CONCLUSION: MRE shows excellent diagnostic performance for predicting significant fibrosis, advanced fibrosis compared with TE and IVIM, while TE and IVIM have comparable diagnostic performance.

Evaluation of liver fibrosis with a monoexponential model of intravoxel incoherent motion magnetic resonance imaging.

To evaluate hepatic fibrosis with a monoexponential model of intravoxel incoherent motion magnetic resonance imaging, and assess the potential application value of intravoxel incoherent motion (IVIM) in diffusion-weighted imaging (IVIM-DWI) in determining staging of liver fibrosis. 28 patients with hepatic fibrosis and 25 volunteers with healthy livers had IVIM examination and conventional MRI. All standard apparent diffusion coefficient (ADC) values of IVIM raw data were post-processed off-line after completion of data collection. All regions of interest (ROIs) were manually positioned by two experienced radiologists. All values of the different fibrosis stages in the study group were compared using independent sample t tests. Using ROC analysis, both AUC values of ADCtotal and ADC0-400-600-800 from study and control group were found to be between 0.8 and 1 for staging fibrosis. The mean ADCtotal and ADC0-400-600-800 values of the liver in the study group were significantly lower than the values in the control group (P < 0.05). Spearman rho correlation analysis was used to determine the relationship among fibrosis stages and the ADCtotal and ADC0-400-600-800 in the study group. As the stage of the fibrosis increased, the values decreased. Significant differences between the two subgroups of liver fibrosis stages were found (P < 0.05). The monoexponential model of IVIM-DWI adopted multiple b values for quantitative analysis of the water molecules diffused in the tissue. It could be used as a noninvasive and valuable method for assessment of liver fibrosis.

Leaf senescence induced by EGY1 defection was partially restored by glucose in Arabidopsis thaliana.

BACKGROUND: Ethylene-dependent gravitropism-deficient and yellow-green 1 (EGY1) protein is required for chloroplast development and photosynthesis conduction. The egy1 deletion mutants have a yellow-green phenotype and reduced granal thylakoids. Furthermore, the yellow-green phenotype of egy1 mutants is more obvious than that of wild-type (WT) plants with increasing leaf age, suggesting an early senescence in the egy1 mutants. However, the relationship between EGY1 functions and leaf senescence still remains poorly understood. RESULTS: We observed that egy1 mutant leaves were more yellow than those of WT (the same age) in Arabidopsis thaliana. In accompany with this phenotype, leaf survival, chlorophyll content, Fv/Fm and soluble protein content decreased, and ion leakage increased significantly in egy1 mutants compared to WT plants. At molecular level, the expressions of senescence-associated genes increased, and photosynthesis genes decreased significantly in the mutants compared to those in WT plants. Furthermore, after darkness treatment, the yellow-green phenotype of egy1 mutants was more obvious than that of WT. These results indicate that the loss-of-function of egy1 gene induces leaf senescence in A. thaliana. In addition, our results showed that the yellow-green phenotype, chlorophyll content and ion leakage of egy1 mutants was partially restored after exogenously applied glucose for 5 weeks. At the same time, the expression of hexokinase 1 (HXK1) and/or senescence-associated gene 12 (SAG12) in egy1 mutants growing on 2 % glucose was lower than that in egy1 mutants without glucose. CONCLUSION: EGY1-defection induced leaf senescence and this senescence was partially restored by glucose in A. thaliana.

Effects of senescence on the expression of BDNF and TrkB receptor in the lateral geniculate nucleus of cats.

To explore the neural mechanisms mediating aging-related visual function declines, we compared the expressions of brain-derived neurotrophic factor (BDNF) and its high affinity receptor-tyrosine kinase B (TrkB) between young and old adult cats. Nissl staining was used to display neurons in each layer of the lateral geniculate nucleus (LGN). The BDNF- and TrkB receptor-immunoreactive neurons were labeled immunohistochemically, observed under optical microscope and photographed. Their neuronal density and immunoreactive intensity were measured. Results showed that the mean density of the Nissl stained neurons in each LGN layer were comparable between old and young adult cats, and their BDNF and TrkB proteins were widely expressed in all LGN layers. However, compared with young adult cats, both the density and optical absorbance intensity of BDNF- and TrkB-immunoreactive cells in each LGN layer in old cats were significantly decreased. These findings indicate that the decreased expressions of BDNF and TrkB proteins in the LGN may be an important factor inducing the compromised inhibition in the central visual nucleus and the functional visual decline in senescent individuals.

Effects of surround suppression on response adaptation of V1 neurons to visual stimuli.

The influence of intracortical inhibition on the response adaptation of visual cortical neurons remains in debate. To clarify this issue, in the present study the influence of surround suppression evoked through the local inhibitory interneurons on the adaptation effects of neurons in the primary visual cortex (V1) were observed. Moreover, the adaptations of V1 neurons to both the high-contrast visual stimuli presented in the classical receptive field (CRF) and to the costimulation presented in the CRF and the surrounding nonclassical receptive field (nCRF) were compared. The intensities of surround suppression were modulated with different sized grating stimuli. The results showed that the response adaptation of V1 neurons decreased significantly with the increase of surround suppression and this adaptation decrease was due to the reduction of the initial response of V1 neurons to visual stimuli. However, the plateau response during adaptation showed no significant changes. These findings indicate that the adaptation effects of V1 neurons may not be directly affected by surround suppression, but may be dynamically regulated by a negative feedback network and be finely adjusted by its initial spiking response to stimulus. This adaptive regulation is not only energy efficient for the central nervous system, but also beneficially acts to maintain the homeostasis of neuronal response to long-presenting visual signals.

Initial study of biexponential model of intravoxel incoherent motion magnetic resonance imaging in evaluation of the liver fibrosis.

BACKGROUND: The diagnosis of liver fibrosis is a difficult task at any time using conventional clinical imaging. Intravoxel incoherent motion (IVIM) can be used to investigate both diffusion and perfusion changes in tissues. This study was designed to determine the value of IVIM in the diagnosis and staging of liver fibrosis. METHODS: IVIM examinations were performed on a GE 3.0T MR scanner in 25 patients with liver fibrosis and 25 healthy volunteers as the control group. Patients with liver fibrosis diagnosis were confirmed by pathology and staged on a scale of F0-4. The standard ADC values and the values of a biexponential model (slow ADC (Dslow), fast ADC (Dfast) and fraction of fast ADC (FF)) were measured in three liver regions per person. The mean standard ADC values, Dslow values, Dfast values and FF values from the study group were compared among the right posterior hepatic lobe, right anterior hepatic lobe and medial segment of the left lobe. Receiver Operating Characteristic (ROC) curves and independent-samples t-tests were used to calculate the mean standard ADC values, Dslow values, Dfast values and FF values from the study group and the control group. Spearman rho correlation analysis was used for the stage of liver fibrosis. The liver fibrosis stages between the groups F0-1 and F2-4, the groups F0-2 and F3-4 were compared. RESULTS: Among the liver fibrosis, there was no significant difference in the mean standard ADC values, Dslow values, Dfast values, and FF values obtained from the right posterior hepatic lobe, right anterior hepatic lobe and medial segment of the left lobe. Using ROC analysis, the Area Under the Curve (AUC) values of standard ADC, Dslow, Dfast, FF were all between 0.7 to 0.9. The mean standard ADC values, Dslow values, Dfast values and FF values of the liver in the study group were significantly lower than the values in the control group (P < 0.05). As the stage of the fibrosis increased, the values decreased by Spearman rho correlation analysis. The mean values (standard ADC, Dslow, Dfast, and FF) of liver fibrosis stages between the groups F0-1 and F2-4, the groups F0-2 and F3-4 showed significant differences (P < 0.05). CONCLUSIONS: IVIM can reflect the conditions of perfusion and diffusion in liver fibrosis and thus distinguish between normal liver and liver fibrosis. The IVIM technique may serve as a valuable tool for detecting and characterizing liver fibrosis, and monitoring its progression in a noninvasive manner.

[Effects of ketamine and urethane on stimulation-induced c-fos expression in neurons of cat visual cortex].

The effects of ketamine and urethane on neuronal activities remain in debate. As a member of immediate early genes family, the expression of c-fos is stimulation dependent and could be treated as an index to evaluate the strength of neural activities. In this study, SABC immunohistochemical techniques were applied to compare the c-fos expression in neurons of the primary visual cortex (V1) of cats and therefore, to evaluate the effects of acute anesthesia with ketamine HCl and uethane on inhibiting neural activities. Our results showed that compared with control cats, there were no significant differences with the average densities of Nissl-stained V1 neurons in each cortical layers of either urethane or ketamine anesthetized cats. In urethane anesthetized cats, neither the average densities nor the immunoreactive intensities of c-fos positive V1 neurons showed significant difference with that of control ones. However, both the average densities and immunoreactive intensities of c-fos positive V1 neurons in ketamine anesthetized cats decreased significantly compared with that of control and urethane anesthetized cats. These results suggested that ketamine has strong inhibitory effects on the activities of visual cortical neurons, whereas urethane did not.

Isolation of high-quality RNA from Reaumuria soongorica, a desert plant rich in secondary metabolites.

RNA isolation is a prerequisite for the study of the molecular mechanisms of stress tolerance in the desert plant Reaumuria soongorica, an extreme xeric semi-shrub. However, R. soongorica that contains high levels of secondary metabolites that co-precipitate with RNA, making RNA isolation difficult. Here the authors propose a new protocol suitable for isolating high-quality RNA from the leaves of R. soongorica. Based on a CTAB method described by Liu et al., the protocol has been improved as follows: the samples were ground with PVPP to effectively inhibit the oxidation of phenolics, contaminating DNA was removed with DNase I, and NaAc was used along with ethanol for precipitation to enhance the RNA yield and shorten the precipitation time. Gel electrophoresis and spectrophotometric analysis indicated that this isolation method provides RNA with no DNA contamination. Moreover, the yield (183.79 ± 40.36 µg/g) and quality were superior to those using the method of Liu et al., which yields RNA with significant DNA contamination at 126.30 ± 29.43 µg/g. Gene amplification showed that the RNA obtained using this protocol is suitable for use in downstream molecular procedures. This method was found to work equally well for isolating RNA from other desert plants. Thus, it is likely to be widely applicable.