During their lifetimes, plants are exposed to different abiotic stress factors eliciting various physiological responses and triggering important defense processes. For UV-B radiation responses in ...forest trees, the genetics and molecular regulation remain to be elucidated. Here, we exposed Pinus tabuliformis Carr., a major conifer from Northern China, to short-term high-intensity UV-B and employed a systems biology approach to characterize the early physiological processes and the hierarchical gene regulation, which revealed a temporal transition from primary to secondary metabolism, the buildup of enhanced antioxidant capacity, and stress-signaling activation. Our findings showed that photosynthesis and biosynthesis of photosynthetic pigments were inhibited, while flavonoids and their related derivates biosynthesis as well as glutathione and glutathione S-transferase mediated antioxidant processes were enhanced. Likewise, stress related phytohormones (jasmonic acid, salicylic acid, and ethylene), kinase, and ROS signal transduction pathways were activated. Biological processes regulated by auxin and karrikin were, for the first time, found to be involved in plant defense against UV-B by promoting the biosynthesis of flavonoids and the improvement of antioxidant capacity in our research system. Our work evaluated the physiological and transcriptome perturbations in a conifer's response to UV-B, and generally, highlighted the necessity of a systems biology approach in addressing plant stress biology.
Paecilomyces bainier 229-7 was obtained after UV irradiation for 8
min in the presence of 0.4% LiCl and selection on potato dextrose media containing 30
mg/mL saponin from Panax notoginseng leaves ...(SPNL). The mutant produces ginsenoside Rd from ginsenoside Rb1 with a bioconversion rate as high as 94.9% under optimized culture conditions in shake flasks when supplied with 20
mg/mL of SPNL. Scale-up in 10-L fermenter resulted in an 89% bioconversion rate. Ginsenoside Rd was purified from the culture medium by a macroporous resin with a chromatographic purity of 92.6%. These results suggest that
P. bainier 229-7 could be useful for the preparation of ginsenoside Rd in the pharmaceutical industry.
Retinopathy of prematurity (ROP) is a vision-threatening ocular disease that occurs in premature infants, but the underlying mechanism is still unclear. Since oxidative stress has been well ...documented in the ROP development, we aimed to investigate whether ferroptosis, a new type of cell death characterized by lipid peroxidation and iron overload, is also involved in ROP. We detected the lipid peroxidation, oxidative stress and the expression of ferroptosis markers in the retina of mouse model of oxygen-induced retinopathy. After ferroptosis inhibitor, ferrostatin-1, was administered by intravitreal injection, ferroptosis marker, lipid peroxidation, retinal vasculature and glial cell activation were examined. We found decreased expression of SLC7A11 and GPX4, increased expression of FTH1 and TFRC, as well as increase of lipid peroxidation in the retina of OIR mice. Ferrostatin-1 administration significantly reduced lipid peroxidation, and also reversed the change of ferroptosis marker. Neovascular area and avascular area were suppressed and the pathological vasculature changes including acellular vessels and ghost pericytes were decreased. Microglial cell and Müller cell activation was not evidently influenced by ferrostatin-1 treatment. Our findings suggest that ferroptosis is involved in the pathological angiogenesis and might be a promising target for ROP therapy.
•Ferroptosis is involved in mouse model of oxygen-induced retinopathy.•Fer-1, a specific inhibitor of ferroptosis, can alleviate retinal pathological angiogenesis in OIR model.•Fer-1 inhibited ferroptosis in retina via regulating the expression of GPX4 and SLC7A11 and decreasing lipid peroxidation.•Ferroptosis seems to be a potential target for treatment of retinopathy of prematurity.
In this paper, we propose a novel semi-supervised multi-label feature selection algorithm and apply it to three different applications: natural scene classification, web page annotation, and yeast ...gene functional classification. Compared with the previous works, there are two advantages of our algorithm: (1) Manifold learning which leverages the underlying geometric structure of the training data is imposed to utilize both labeled and unlabeled data. Besides, the underlying manifold structure is guaranteed to be clear by using the l1-norm regularization. (2) Shared subspace learning which has shown its efficiency in multi-label learning scenarios, is also considered in our feature learning algorithm. The proposed objective function involves l2,1-norm and l1-norm, making it non-smooth and difficult to solve. We also design an efficient iterative algorithm to optimize it. Experimental results demonstrate the effectiveness of our algorithm compared with sate-of-the-art algorithms on different tasks.
•A semi-supervised multi-label feature selection method leveraging shared information among multiple labels is proposed.•A l1-norm based graph matrix is imposed to capture a clear underlying manifold structure.•A l2,1-norm is imposed to select the most representative features.•An efficient iterative algorithm is proposed to optimize the non-smooth objective function.
Tie2-expressing monocytes (TEMs) are found in various tumors, involved in forming tumor blood vessels and expressing several important proangiogenic factors. The goals of this study were to evaluate ...the value of TEMs in diagnosing and predicting the prognosis of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).
Flow cytometry was performed to identify and count TEMs in peripheral blood monocytes from HCC patients (n = 84) receiving hepatectomy, HBV cirrhotic patients (n = 21), benign tumors patients (n = 15) and healthy volunteers (n = 23). Angiopoietin-2 (Ang-2) levels in the plasma were determined by enzyme linked immunosorbent assay. The distribution of TEMs in tumor tissue was observed by immunofluorescence staining. Then we determined the vascular area as a percentage of tumor area (vascular area/tumor area) by immunohistochemical staining. Finally the prognostic significance of TEMs and other clinicopathologic factors was evaluated.
Percentage of TEMs in peripheral blood monocytes significantly increased in HCC patients compared with HBV cirrhotic patients and healthy donors (both P< 0.001). However there was no significance in benign liver tumor (P = 0.482). In addition, the percentage of circulating TEMs was positively correlated with plasma Ang-2 concentration (P<0.001, r2 = 0.294) and vascular area/tumor area (P<0.001, r2 = 0.126). Furthermore the percentage of intratumoral TEMs was significantly higher than that of paratumoral TEMs (P<0.001). Increased circulating TEMs was associated with poor overall survival (P = 0.043) and a shorter time to recurrence (P = 0.041). Multivariate Cox analysis also revealed that the percentage of TEMs in peripheral blood was an independent factor for HCC patients' prognosis.
TEMs may promote angiogenesis in HCC regarding the angiopoietin/Tie2 signal pathway. Percentage of TEMs in peripheral blood monocytes may be applied as a biomarker for identifying HBV-related HCC and predicting the prognosis of these patients after resection.
Tuberculous meningitis (TBM) is the most serious form of extrapulmonary tuberculosis caused by
, and is characterized by high morbidity and mortality. Unfortunately, it is difficult to distinguish ...TBM from bacterial meningitis (BM) based on clinical features alone. The latest diagnostic tests and neuroimaging methods are still not available in many developing countries. This study aimed to develop a simple diagnostic algorithm based on clinical and laboratory test results as an early predictor of TBM in South China.
A retrospective study was conducted to compare the clinical and laboratory characteristics of 114 patients with TBM and 47 with BM. Multivariate logistic regression analysis was performed on the characteristics of independently predicted TBM to develop a new diagnostic rule.
Five characteristics were predictive of a diagnosis of TBM: duration of symptoms before admission; tuberculous symptoms; white blood cell (WBC) count, total cerebrospinal fluid WBC count, and cerebrospinal fluid chloride concentration. The sensitivity and specificity of the new scoring system developed in this study were 81.6 and 93.6%, respectively.
The new scoring system proposed in this study can help physicians empirically diagnose TBM and can be used in countries and regions with limited microbial and radiological resources.
Necrosis is programmed and is one of the main forms of cell death in the pathological process in cardiac diseases. MicroRNAs (miRNAs) have emerged as key gene regulators in many diseases. However, ...how miRNAs contribute to programmed necrosis is poorly defined. Here we report that miR-2861 and adenine nucleotide translocase 1 (ANT1) constitute an axis that regulates necrotic cell death in the heart. Our results show that ANT1 inhibits H2O2-induced cardiomyocytes necrosis. ANT1 also antagonizes myocardial necrosis in a mouse ischemia/reperfusion (I/R) model. We further demonstrate that miR-2861 directly binds to the coding sequence of ANT1 and suppresses the expression of ANT1 mRNA and protein. MiR-2861 induces necrotic cell death. In contrast, knockdown of miR-2861 attenuates H2O2-induced necrosis in cardiomyocytes. Also, miR-2861 knockdown protects heart from I/R injury and necrotic cell death in vivo. MiR-2861 regulates necrosis and myocardial infarction through targeting ANT1. Collectively, these data identify miR-2861 and ANT1 as two novel regulators of cardiomyocyte necrosis and myocardial infarction, and suggest potential therapeutic targets in treatment of cardiac diseases.
•ANT1 antagonizes H2O2- or I/R-induced necrosis in cardiomyocytes.•miR-2861 binds to the coding sequence of ANT1 and triggers ANT1 mRNA degradation.•miR-2861 regulates programmed necrosis by targeting ANT1 in the heart.
This study aimed to investigate the gap between adaptive functioning and cognitive functioning, especially verbal and nonverbal intelligence quotient (IQ) in Chinese children with ASD. We ...systematically explored cognitive functioning, ASD severity, early signs of developmental abnormalities, and socioeconomic factors as mediating factors of adaptive functioning. We enrolled 151 children (age: 2.5?6 years) with ASD and categorized them into one group with IQ ≥ 70 and another with IQ < 70. The two groups were calibrated for age, age at diagnosis, and IQ, and the relationship of adaptive skills with vocabulary acquisition index (VAI) and nonverbal index (NVI) were separately analyzed. Results show that the gap between IQ and adaptive functioning was significant in children with ASD having IQ ≥ 70, with both VAI and NVI showing statistically significant differences (all P < 0.001). VAI correlated positively with scores for overall adaptive skills and specific domains, whereas NVI had no significant correlations with adaptive skill scores. Age of first walking unaided had an independent positive correlation (all P < 0.05) with scores of adaptive skills and specific domains. IQ-adaptive functioning gap is significant in children with ASD having IQ ≥ 70, suggesting that defining "high-functioning autism" merely on the basis of IQ is not appropriate. Verbal IQ and early signs of motor development are specific and possible predictors of adaptive functioning in children with ASD, respectively.
Resting-state functional magnetic resonance imaging (fMRI) studies have uncovered the disruptions of functional brain networks in primary insomnia (PI) patients. However, the etiology and ...pathogenesis underlying this disorder remains ambiguous, and the insomnia related symptoms are influenced by a complex network organization in the brain. The purpose of this study was to explore the abnormal intrinsic functional hubs in PI patients using a voxel-wise degree centrality (DC) analysis and seed-based functional connectivity (FC) approach.
A total of 26 PI patients and 28 healthy controls were enrolled, and they underwent resting-state fMRI. Degree centrality was measured across the whole brain, and group differences in DC were compared. The peak points, which significantly altered DC between the two groups, were defined as the seed regions and were further used to calculate FC of the whole brain. Later, correlation analyses were performed between the changes in brain function and clinical features.
Primary insomnia patients showed DC values lower than healthy controls in the left inferior frontal gyrus (IFG) and middle temporal gyrus (MTG) and showed a higher DC value in the right precuneus. The seed-based analyses demonstrated decreased FC between the left MTG and the left posterior cingulate cortex (PCC), and decreased FC was observed between the right precuneus and the right lateral occipital cortex. Reduced DC in the left IFG and decreased FC in the left PCC were positively correlated with the Pittsburgh sleep quality index and the insomnia severity index.
This study revealed that PI patients exhibited abnormal intrinsic functional hubs in the left IFG, MTG, and the right precuneus, as well as abnormal seed-based FC in these hubs. These results contribute to better understanding of how brain function influences the symptoms of PI.