Non-symmetric responses of leaf onset date to natural warming and cooling in northern ecosystems.

The northern hemisphere has experienced regional cooling, especially during the global warming hiatus (1998-2012) due to ocean energy redistribution. However, the lack of studies about the natural cooling effects hampers our understanding of vegetation responses to climate change. Using 15,125 ground phenological time series at 3,620 sites since the 1950s and 31-year satellite greenness observations (1982-2012) covering the warming hiatus period, we show a stronger response of leaf onset date (LOD) to natural cooling than to warming, i.e. the delay of LOD caused by 1°C cooling is larger than the advance of LOD with 1°C warming. This might be because cooling leads to larger chilling accumulation and heating requirements for leaf onset, but this non-symmetric LOD response is partially offset by warming-related drying. Moreover, spring greening magnitude, in terms of satellite-based greenness and productivity, is more sensitive to LOD changes in the warming area than in the cooling. These results highlight the importance of considering non-symmetric responses of spring greening to warming and cooling when predicting vegetation-climate feedbacks.

Mathematical models for intraoperative prediction of metastasis to regional lymph nodes in patients with clinical stage I non-small cell lung cancer.

It remains challenging to determine the regions of metastasis to lymph nodes during operation for clinical stage I non-small cell lung cancer (NSCLC). This study aimed to establish intraoperative mathematical models with nomograms for predicting the hilar-intrapulmonary node metastasis (HNM) and the mediastinal node metastasis (MNM) in patients with clinical stage I NSCLC. The clinicopathological variables of 585 patients in a derivation cohort who underwent thoracoscopic lobectomy with complete lymph node dissection were retrospectively analyzed for their association with the HNM or the MNM. After analyzing the variables, we developed multivariable logistic models with nomograms to estimate the risk of lymph node metastasis in different regions. The predictive efficacy was then validated in a validation cohort of 418 patients. It was confirmed that carcinoembryonic antigen (>5.75 ng/mL), CYFRA211 (>2.85 ng/mL), the maximum diameter of tumor (>2.75 cm), tumor differentiation (grade III), bronchial mucosa and cartilage invasion, and vascular invasion were predictors of HNM, and carcinoembryonic antigen (>8.25 ng/mL), CYFRA211 (>2.95 ng/mL), the maximum diameter of tumor (>2.75 cm), tumor differentiation (grade III), bronchial mucosa and cartilage invasion, vascular invasion, and visceral pleural invasion were predictors of MNM. The validation of the prediction models based on the above results demonstrated good discriminatory power. Our predictive models are helpful in the decision-making process of specific therapeutic strategies for the regional lymph node metastasis in patients with clinical stage I NSCLC.

Improving effects of eplerenone on atrial remodeling induced by chronic intermittent hypoxia in rats.

OBJECTIVE: Atrial fibrillation (AF) is closely associated with the overactivation of the renin-angiotensin-aldosterone system. Large cohort studies and recent meta-analyses have shown that the utilization of mineralocorticoid receptor antagonists has positive effects on the prevention and development of AF. This study aimed to investigate the effects of eplerenone on atrial remodeling in AF model rats and elucidate its intrinsic mechanism. METHODS: Ninety male Sprague-Dawley rats were randomly divided into the control group, chronic intermittent hypoxia (CIH) group, and CIH-eplerenone intervention (CIH-E) group. Rats in the CIH and CIH-E groups received CIH for 6 weeks, and rats in the CIH-E group were additionally administered eplerenone gavage (10 mg/kg/d). After modeling, the baseline parameters of each group were examined. Histopathology, molecular biology, isolated electrophysiology, and patch clamp experiments were performed after sampling. RESULTS: Compared with the control group, rats in the CIH group showed atrial enlargement, significant aggravated fibrosis, upregulated JAK/STAT3 pathway, shortened effective refractory period (ERP), increased AF inducibility, and decreased peak current density of characteristic voltage-gated ion channels in atrial myocytes. After eplerenone intervention, rats in the CIH-E group had a smaller atrial diameter than those in the CIH group. Furthermore, downregulated JAK/STAT3 pathway, prolonged ERP, decreased AF inducibility, and increased peak current density of characteristic ion channels were also observed in the CIH-E group. CONCLUSIONS: CIH induced significant atrial remodeling in rats and eplerenone significantly ameliorated the atrial remodeling caused by CIH. This could be attributed to the downregulation of the JAK/STAT3 pathway and the increase in the characteristic ion current density of atrial myocytes.

Ameliorative Impact of Liraglutide on Chronic Intermittent Hypoxia-Induced Atrial Remodeling.

Atrial fibrillation (AF) is the most frequent form of clinical cardiac arrhythmias. Previous evidence proved that atrial anatomical remodeling (AAR) and atrial electrical remodeling (AER) are crucial for the progression and maintenance of AF. This study is aimed at investigating the impact of the glucagon-like peptide-1 (GLP-1) receptor agonist, Liraglutide (Lir), on atrial remodeling (AR) mouse model induced by chronic intermittent hypoxia (CIH). C57BL/6 mice were categorized randomly into the control, Lir, CIH, and CIH+Lir groups. CIH was performed in CIH and CIH+Lir groups for 12 weeks. Lir (0.3 mg/kg/day, s.c) was administered to the Lir and CIH+Lir groups for four weeks, beginning from the ninth week of CIH. Meanwhile, echocardiography and right atrial endocardial electrophysiology via jugular vein, as well as induction rate and duration of AF, were evaluated. Masson and Sirius red staining assays were utilized to assess the extent of fibrosis in the atrial tissue of the mice. Immunohistochemical staining, RT-qPCR, and Western blotting were performed to evaluate the marker levels of AAR and AER and the expression of genes and proteins of the miR-21/PTEN/PI3K/AKT signaling pathway, respectively. ELISA was also performed to evaluate the changes of serum inflammatory factor levels. The CIH group exhibited significant AR, increased atrial fibrosis, and a higher incidence rate of AF compared to the control group. Lir could significantly downregulate the protein expression level in the PI3K/p-AKT pathway and upregulated that of phosphatase and tensin homolog deleted on chromosome ten (PTEN). Moreover, Lir downregulated the expression of miR-21. However, the protein expressions of CACNA1C and KCNA5 in atrial tissue were not changed significantly. In addition, Lir significantly attenuated the levels of markers of inflammation (TNF-α and IL-6) in the serum. In the mouse model of CIH, Lir treatment could ameliorate AR by the miR-21/PTEN/PI3K/AKT signaling pathway and modulation of inflammatory responses.

Spatial quantification method of grassland utilization intensity on the Qinghai-Tibetan Plateau: A case study on the Selinco basin.

Existing methods for spatial quantification of grassland utilization intensity cannot meet the demand for accurate detection of the spatial distribution of grassland utilization intensity in the Qinghai-Tibetan Plateau with high spatial resolution. In this paper, a method based on remote-sensing observations and simulations of grassland growth dynamics is proposed. The grassland enhanced vegetation index (EVI) time-series curve during the growing season characterizes the growth of grassland in the corresponding pixel; The deviation between the observed and potential EVI curves indicates the disturbance on grassland growth imposed by human activities, and it can characterize the grassland utilization intensity during the growing season. Based on the main idea described above, absolute and relative disturbances are calculated and used as quantitative indicators of grassland utilization intensity defined from different perspectives. Livestock amount at the pixel scale is obtained by pixel-by-pixel calculations based on the function relationship at the township scale between absolute disturbance and livestock density, which is specific quantitative indicator that considers the mode of grassland utilization. In simulating the potential EVI of grassland, the lag and accumulation effects of meteorological factors are investigated at the daily scale using a multi-objective genetic algorithm. Further, the nonlinear functions between multiple environmental factors (e.g., grassland type, topography, soil, meteorology) and the grassland EVI are established using an error back-propagation feedforward artificial neural network (ANN-BP) with parameter optimization. Finally, the potential EVIs of all grassland pixels are simulated on the basis of this model. The method is applied to the Selinco basin on the Qinghai-Tibetan Plateau and validated by examining the spatial consistency of the results with township-scale livestock density and grazing pressure. The final results indicate that the proposed method can accurately detect the spatial distribution of grassland utilization intensity which is appliable in the similar regions.

Postoperative diffused alveolar hemorrhage complicated by pneumonia after lung cancer surgery in a patient with liver cirrhosis: a case report and review of literatures.

Postoperative pulmonary complications remain a challenge after pulmonary surgery in patients with severe cirrhosis in spite of advances in perioperative management. Diffused alveolar hemorrhage (DAH) is a pernicious clinical syndrome that is often primarily assumed to be atypical pneumonia. We report a case of a 54-year-old man presented with shortness of breath on the first post-operation day, who was successfully treated by left superior segmentectomy and right superior wedge resection. Imaging studies showed patchy infiltrates scattered throughout both lungs. Klebsiella pneumoniae and Candida albicans were found in the sputum culture. Management strategy was designed to provide adequate respiratory support, treat underlying infections and control inflammation. Non-invasive ventilator assisted ventilation was performed. We proposed that cirrhosis-induced DAH should be considered in the differential diagnosis of early pulmonary complications after pulmonary surgery. Early diagnosis and proper but not aggressive treatment protocol are crucial for recovery.

Sacubitril/Valsartan Improves Left Atrial and Left Atrial Appendage Function in Patients With Atrial Fibrillation and in Pressure Overload-Induced Mice.

LCZ696 (sacubitril/valsartan) is an angiotensin receptor-neprilysin inhibitor and has shown beneficial effects in patients with heart failure. However, whether LCZ696 protects against left atrial (LA) and LA appendage (LAA) dysfunction is still unclear. The present study aimed to assess the efficacy of LCZ696 for improving the function of LA and LAA. We performed both a retrospective study comparing LCZ696 with angiotensin receptor blockers (ARBs) to assess the efficacy of LCZ696 in patients with atrial fibrillation and an animal study in a mouse model with pressure overload. LA peak systolic strain, LAA emptying flow velocity, and LAA ejection fraction (LAAEF) were significantly increased in patients with LCZ696 as compared with ARBs (p = 0.024, p = 0.036, p = 0.026, respectively). Users of LCZ696 had a lower incidence of spontaneous echocardiography contrast (p = 0.040). Next, patients were divided into two groups (LAAEF ≤ 20% and > 20%). Administration of LCZ696 in patients with LAAEF > 20% was more frequent than LAAEF ≤ 20% (p = 0.032). Even after controlling for LAA dysfunction-related risk factors (age, atrial fibrillation type, old myocardial infarction, hypertension, congestive heart failure, and prior stroke or transient ischemic attack), use of LCZ696 remained significantly associated with reduced probability of LAAEF ≤ 20% [odds ratio = 0.011; 95% confidence interval (0.000-0.533), p = 0.023]. To further confirmed effect of LCZ696 in LA function, we constructed a post-transverse aortic constriction model in mice. Mice with LCZ696 treatment showed lower LA dimension and higher left ventricular ejection fraction and LAA emptying flow velocity as compared with mice with vehicle or valsartan treatment. Meanwhile, as compared with vehicle or valsartan, LCZ696 significantly decreased LA fibrosis in mice. In summary, we provide evidence that LCZ696 may be more effective in improving LA and LAA function than ARBs in both humans and mice, which suggests that LCZ696 might be evaluated as a direct therapeutic for atrial remodeling and AF.

Characterization of apoptosis and proliferation in esophageal carcinoma EC109 cells following siRNA-induced down-regulation of TRAF6.

Tumor necrosis factor receptor-associated factor 6 (TRAF6) is an activator of the NF-κB transcription factor. NF-κB is involved in a variety of inflammatory, anti-apoptotic, and gene regulatory pathways and was recently found to be over-expressed in esophageal cancer cells. Here we investigated the function of TRAF6 in the esophageal cancer cell line EC109. siRNA targeting TRAF6 was introduced into EC109 cells and TRAF6 mRNA and protein levels were subsequently examined via RT-PCR and western blotting. Rates of apoptosis and cell proliferation were also measured using flow cytometry, ethynyl deoxyuridine (EdU), and CCK-8 (Cell Counting Kit-8) assays. The real-time PCR array was applied to profile the expression of TRAF6 related genes. TRAF6-siRNA reduced TRAF6 mRNA and protein expressions. NF-κB p65 protein expression was decreased in TRAF6-targeting siRNA-transfected cells compared to cells of the negative control. TRAF6-siRNA also significantly inhibited proliferation and enhanced apoptosis of EC109 cells. These studies suggested that TRAF6 was required for NF-κB activation in EC109 cells and it may be a good molecular target for suppressing the survival and proliferation of esophageal cancer cells.