Revealing Impacts of Human Activities and Natural Factors on Dynamic Changes of Relationships among Ecosystem Services: A Case Study in the Huang-Huai-Hai Plain, China.

Understanding the dynamic changes of relationships between ecosystem services (ESs) and their dominant factors can effectively adjust human activities to adapt proactively to global climate change. In this study, the Huang-Huai-Hai Plain (HHHP) was selected to assess the dynamics of four key ESs (NPP, net primary productivity; WY, water yield; SC, soil conservation; FP, food production) from 2000 to 2020. The constraint lines of interactions among ESs were extracted based on a segmented quantile regression model. On this basis, the effects of both human activities and natural factors on the key features of the interactions between ESs were quantified with the help of automatic linear model. The results indicated that two types of constraint relationships, including exponential and humped-shaped, existed among the six pairs of ESs. In the past two decades, small changes in NPP thresholds would lead to large variations in other ESs thresholds. Precipitation and normalized difference vegetation index were the key factors to determine the constraint strength of ESs in the HHHP. The potential maximum value of WY in the HHHP could be increased by adjusting landscape shape to make it more complicated. This study helps to improve the potential of target ESs and provides a decision-making basis for promoting regional sustainable development.

Treatment efficacy of tigecycline in comparison to cefoperazone/ sulbactam alone or in combination therapy for carbapenenm-resistant Acinetobacter baumannii infections.

Tigecycline (TGC) and cefoperazone/sulbactam (CPS) both have been shown good in vitro activity against carbapenem-resistant Acinetobacter baumannii (CRAB) isolates. We aim to compare the efficacy of TGC versus CPS for CRAB infections. We conducted a retrospective cohort study of patients with CRAB at a single center in China from 2013 to 2015. Outcomes comprised in-hospital mortality, clinical and microbiological response. The method of inverse probability of treatment weighting and multivariable logistic regression analysis incorporated with propensity score were employed to estimate the effect of treatment groups. There were 130 subjects included in our study. The patients in TGC, CPS and TGC plus CPS combination group were 42, 66, and 22, respectively. After adjustment, in-hospital mortality was lower in CPS group than TGC group (weighted OR 0.173; 95% CI 0.06-0.497; P=0.001) but without differences in clinical success and microbiological eradication (P>0.05). TGC monotherapy had a similar outcome with TGC plus CPS combination group. This is the first study comparing the efficacy of tigecycline and cefoperazone/sulbactam for CRAB infections. Cefoperazone/sulbactam appears to be more efficacious than tigecycline during treatment.

Transgelin 2 Promotes Paclitaxel Resistance, Migration, and Invasion of Breast Cancer by Directly Interacting with PTEN and Activating PI3K/Akt/GSK-3ß Pathway.

MDR and tumor migration and invasion are still the main obstacles to effective breast cancer chemotherapies. Transgelin 2 has recently been shown to induce drug resistance, tumor migration, and invasion. The aim of this study was to determine the biological functions of Transgelin 2 and the mechanism underlying how Transgelin 2 induces paclitaxel (PTX) resistance and the migration and invasion of breast cancer. We detected that the protein level of Transgelin 2 was significantly upregulated in breast cancer tissues compared with adjacent nontumor tissues. A bioinformatics analysis indicated that Transgelin 2 was significantly related to clinicopathologic parameters and patient prognosis. Overexpression of Transgelin 2 enhanced the migration and invasion of human breast cancer cells and decreased the sensitivity of breast cancer cells to paclitaxel. Meanwhile, the tumorigenesis and metastasis of breast cancer cells were also enhanced by Transgelin 2 overexpression in vivo Moreover, Transgelin 2 overexpression activated the PI3K/Akt/GSK-3ß pathway by increasing the phosphorylation levels of Akt and GSK-3ß and decreasing the expression of PTEN. We also found that Transgelin 2 could directly interact with PTEN and was located upstream of PTEN. Furthermore, the PI3K/Akt pathway inhibitor MK-2206 reversed the resistance to paclitaxel and inhibited the migration and invasion of breast cancer cells. These findings indicate that Transgelin 2 promotes paclitaxel resistance and the migration and invasion of breast cancer by directly interacting with PTEN and activating the PI3K/Akt/GSK-3ß pathway. Transgelin 2 may therefore be useful as a novel biomarker and therapeutic target for breast cancer.

Network meta-analysis and pharmacoeconomic evaluation of antibiotics for the treatment of patients infected with complicated skin and soft structure infection and hospital-acquired or ventilator-associated penumonia.

Background: Infections due to methicillin-resistant Staphylococcus aureus (MRSA) cause serious health risks and significant economic burdens and the preferred drugs are still controversial. Methods: We performed a network meta-analysis (NMA) to compare the efficacy and safety of antibiotics used to treat inpatients with complicated skin and soft structure infections (cSSSI) or hospital-acquired or ventilator-associated pneumonia (HAP/VAP). We also developed a decision tree model to assess the cost-effectiveness of antibiotics. Results: Forty-nine randomized controlled trials met the inclusion criteria (34 for cSSSI, 15 for HAP/VAP) and compared the efficacy and safety of 16 antibiotics. For cSSSI, NMA indicated that for clinical cure, linezolid was superior than vancomycin (odds ratio (OR) 1.55, 95% confidence interval (CI) 1.19-2.02), while tedizolid (OR 1.39, CI 0.70-2.76) was similar to vancomycin. In terms of safety, there were no significant differences between any two interventions on total adverse events. Based on drug and hospital costs in America, the incremental cost-effectiveness ratios (ICERs) per life-year saved for linezolid and tedizolid compared with vancomycin were US$2833 and US$5523. For HAP/VAP, there were no significant effects either for clinical cure or for safety endpoints between linezolid and vancomycin in NMA. ICERs per life-year saved for linezolid compared with vancomycin were US$2185. Conclusion: In these clinical trials, considering efficacy, safety, and cost-effectivenes, linezolid and tedizolid showed their superiority in MRSA cSSSI; while linezolid might be recommended to treat MRSA pneumonia. Although vancomycin was not cost-effective in pharmacoeconomic evaluation, it is still the first-line treatment for MRSA infection in the clinical practice. This study might provide new insights of therapeutic choices for patients with MRSA infections whilst awaiting the arrival of higher quality evidence.

Transgelin-2 expression in breast cancer and its relationships with clinicopathological features and patient outcome.

BACKGROUND: Transgelin-2 is an actin-binding protein that is widely expressed in various tissues and organs of the body, and reportedly may participate in the development and progression of multiple cancers. However, the clinical significance of transgelin-2 still remains controversial. We, therefore, aimed to determine the expression of transgelin-2 in breast cancer as well as its correlation with the tumorigenesis, progression and prognosis of human breast cancer. METHODS: We collected tissues of 58 breast cancer patients from our hospital and 1090 samples from The Cancer Genome Atlas (TCGA) database. X-tile software was used to divide the transgelin-2 mRNA expression level in the database, logistic regression model was used to identify independent factors influencing transgelin-2 mRNA expression, and then Cox regression and Kaplan-Meier analysis were used to find factors that influence survival of breast cancer. RESULTS: Transgelin-2 was significantly overexpressed in breast cancer tissues from our hospital and receiver operating characteristic (ROC) curve indicated that transgelin-2 may have diagnostic value. Meanwhile, estrogen receptor (ER) was in inverse correlation with transgelin-2 protein and mRNA expression, and transgelin-2 expression was positively correlated with Ki67 in breast cancer tissues. Logistic regression model revealed that TNM stage, ER and progesterone receptor (PR) status were independent factors for transgelin-2 mRNA expression. Patients with high transgelin-2 mRNA expression showed a poor survival and the trend was statistically significant only in ER-negative patients. CONCLUSIONS: Transgelin-2 was expressed significantly higher in breast cancer cells and correlated with some clinicopathological factors. High transgelin-2 expression might predict poor prognosis for ER-negative patients.

SE translation mRNA overexpression: a potential prognostic predictor in breast cancer.

BACKGROUND: Patient SE translation (SET) belongs to histone chaperone nucleosome assembly protein family and has been confirmed that it is associated with carcinogenesis, tumor progression and patient outcome. In this study, we aim at assessing the prognostic value of SET mRNA, the function and pathway of SET and its related genes in breast cancer. METHODS: The clinicopathological and prognostic significance of SET was assessed by the molecular taxonomy of breast cancer international consortium (METABRIC) database (n=1,904). Additionally, based on the data and network of SET and its related genes from cBioPortal website, their function in the progression of breast cancer was also explored. RESULTS: SET mRNA overexpression was a significant predictor of a poor prognosis (P=0.0006). The two signaling pathways associated with SET were the facilitating function of condensin II on mitosis and the accelerated transportation of tumor cell mRNA towards the extranuclear position, and SET acted to suppress condensin II and stabilize mRNA. CONCLUSIONS: Owing to the regulation of chromosome condensation and stabilization of tumor cell mRNA, overexpression of SET is correlated with aggressive phenotypes and facilitates tumor proliferation and deterioration. SET may act as a valuable prognosis biomarker in breast cancer.

Utility of posaconazole therapeutic drug monitoring and assessment of plasma concentration threshold for effective prophylaxis of invasive fungal infections: a meta-analysis with trial sequential analysis.

BACKGROUND: Posaconazole therapeutic drug monitoring (TDM) is increasingly used in clinical practice. However, the utility of posaconazole TDM and the target of posaconazole plasma concentration for clinical successful prophylaxis remain uncertain and controversial. The aim of this study was to evaluate posaconazole exposure-response relationship and determine an optimum posaconazole concentration for prophylaxis against invasive fungal infections (IFIs). METHODS: Bibliographic databases were searched (from inception to September 2017) to select studies including the clinical outcomes below and above concentration cut-off value of 0.5 mg/L and 0.7 mg/L. The reliability of the results were evaluated with trial sequential analysis (TSA). RESULTS: Twenty-eight studies with 1930 patients included were analyzed. The results of our pooled analysis demonstrated that patients with posaconazole plasma concentrations over 0.5 mg/L were twice more likely to achieve successful responses compared with those with lower concentrations (odds ratio, OR = 1.98, 95% confidence interval, CI 1.09-3.58, P = 0.02) while the threshold, 0.7 mg/L showed no significant difference (OR = 1.84, 95% CI 0.94-3.63, P = 0.08). The TSA results showed that there was sufficient information to support these findings. CONCLUSIONS: An optimal posaconazole concentration target of 0.5 mg/L is suggested to ensure the clinical prophylactic efficacy and may help reduce the dosage and dose-dependent toxicity comparing with the target of 0.7 mg/L.

Understanding the Patterns and Drivers of Air Pollution on Multiple Time Scales: The Case of Northern China.

China's rapid economic growth during the past three decades has resulted in a number of environmental problems, including the deterioration of air quality. It is necessary to better understand how the spatial pattern of air pollutants varies with time scales and what drive these changes. To address these questions, this study focused on one of the most heavily air-polluted areas in North China. We first quantified the spatial pattern of air pollution, and then systematically examined the relationships of air pollution to several socioeconomic and climatic factors using the constraint line method, correlation analysis, and stepwise regression on decadal, annual, and seasonal scales. Our results indicate that PM2.5 was the dominant air pollutant in the Beijing-Tianjin-Hebei region, while PM2.5 and PM10 were both important pollutants in the Agro-pastoral Transitional Zone (APTZ) region. Our statistical analyses suggest that energy consumption and gross domestic product (GDP) in the industry were the most important factors for air pollution on the decadal scale, but the impacts of climatic factors could also be significant. On the annual and seasonal scales, high wind speed, low relative humidity, and long sunshine duration constrained PM2.5 accumulation; low wind speed and high relative humidity constrained PM10 accumulation; and short sunshine duration and high wind speed constrained O3 accumulation. Our study showed that analyses on multiple temporal scales are not only necessary to determine key drivers of air pollution, but also insightful for understanding the spatial patterns of air pollution, which was important for urban planning and air pollution control.

Transgelin-2: A potential oncogenic factor.

Actin-binding proteins are proteins that could bind to actin or actin fibers. As a member of actin-binding proteins, Transgelin-2 is expressed in smooth muscle cells and non-smooth muscle cells, and its gene, TAGLN2, is differently expressed in all cells and tissues. The deregulation of Transgelin-2 is considered to be correlated with progression of many kinds of diseases, especially the development of malignant tumors, such as invasion, metastasis, and resistance, yet the function and mechanism of action of Transgelin-2 remain elusive. Therefore, we reviewed the basic characteristics and function of Transgelin-2 and its biological role in various types of diseases in order to provide the theoretical basis for further research and new perspectives on cancer development.

Impacts of changes in climate and landscape pattern on ecosystem services.

The restoration of degraded vegetation can effectively improve ecosystem services, increase human well-being, and promote regional sustainable development. Understanding the changing trends in ecosystem services and their drivers is an important step in informing decision makers for the development of reasonable landscape management measures. From 2001 to 2014, we analyzed the changing trends in five critical ecosystem services in the Xilingol Grassland, which is typical of grasslands in North China, including net primary productivity (NPP), soil conservation (SC), soil loss due to wind (SL), water yield (WY) and water retention (WR). Additionally, we quantified how climatic factors and landscape patterns affect the five ecosystem services on both annual and seasonal time scales. Overall, the results indicated that vegetation restoration can effectively improve the five grassland ecosystem services, and precipitation (PPT) is the most critical climatic factor. The impact of changes in the normalized difference vegetation index (NDVI) was most readily detectable on the annual time scale, whereas the impact of changes in landscape pattern was most readily detectable on the seasonal time scale. A win-win situation in terms of grassland ecosystem services (e.g., vegetation productivity, SC, WR and reduced SL) can be achieved by increasing grassland aggregation, partitioning the largest grasslands, dividing larger areas of farmland into smaller patches, and increasing the area of appropriate forest stands. Our work may aid policymakers in developing regional landscape management schemes.

Quantifying the effect of trend, fluctuation, and extreme event of climate change on ecosystem productivity.

Climate change comprises three fractions of trend, fluctuation, and extreme event. Assessing the effect of climate change on terrestrial ecosystem requires an understanding of the action mechanism of these fractions, respectively. This study examined 11 years of remotely sensed-derived net primary productivity (NPP) to identify the impacts of the trend and fluctuation of climate change as well as extremely low temperatures caused by a freezing disaster on ecosystem productivity in Hunan province, China. The partial least squares regression model was used to evaluate the contributions of temperature, precipitation, and photosynthetically active radiation (PAR) to NPP variation. A climatic signal decomposition and contribution assessment model was proposed to decompose climate factors into trend and fluctuation components. Then, we quantitatively evaluated the contributions of each component of climatic factors to NPP variation. The results indicated that the total contribution of the temperature, precipitation, and PAR to NPP variation from 2001 to 2011 in Hunan province is 85 %, and individual contributions of the temperature, precipitation, and PAR to NPP variation are 44 % (including 34 % trend contribution and 10 % fluctuation contribution), 5 % (including 4 % trend contribution and 1 % fluctuation contribution), and 36 % (including 30 % trend contribution and 6 % fluctuation contribution), respectively. The contributions of temperature fluctuation-driven NPP were higher in the north and lower in the south, and the contributions of precipitation trend-driven NPP and PAR fluctuation-driven NPP are higher in the west and lower in the east. As an instance of occasionally triggered disturbance in 2008, extremely low temperatures and a freezing disaster produced an abrupt decrease of NPP in forest and grass ecosystems. These results prove that the climatic trend change brought about great impacts on ecosystem productivity and that climatic fluctuations and extreme events can also alter the ecosystem succession process, even resulting in an alternative trajectory. All of these findings could improve our understanding of the impacts of climate change on the provision of ecosystem functions and services and can also provide a basis for policy makers to apply adaptive measures to overcome the unfavorable influence of climate change.

The potential effects of climate change on the distribution and productivity of Cunninghamia lanceolata in China.

Climate changes may have immediate implications for forest productivity and may produce dramatic shifts in tree species distributions in the future. Quantifying these implications is significant for both scientists and managers. Cunninghamia lanceolata is an important coniferous timber species due to its fast growth and wide distribution in China. This paper proposes a methodology aiming at enhancing the distribution and productivity of C. lanceolata against a background of climate change. First, we simulated the potential distributions and establishment probabilities of C. lanceolata based on a species distribution model. Second, a process-based model, the PnET-II model, was calibrated and its parameterization of water balance improved. Finally, the improved PnET-II model was used to simulate the net primary productivity (NPP) of C. lanceolata. The simulated NPP and potential distribution were combined to produce an integrated indicator, the estimated total NPP, which serves to comprehensively characterize the productivity of the forest under climate change. The results of the analysis showed that (1) the distribution of C. lanceolata will increase in central China, but the mean probability of establishment will decrease in the 2050s; (2) the PnET-II model was improved, calibrated, and successfully validated for the simulation of the NPP of C. lanceolata in China; and (3) all scenarios predicted a reduction in total NPP in the 2050s, with a markedly lower reduction under the a2 scenario than under the b2 scenario. The changes in NPP suggested that forest productivity will show a large decrease in southern China and a mild increase in central China. All of these findings could improve our understanding of the impact of climate change on forest ecosystem structure and function and could provide a basis for policy-makers to apply adaptive measures and overcome the unfavorable influences of climate change.

[Intermolecular hydrogen bond between protein and flavonoid and its contribution to the stability of the flavonoids].

The interactions between three proteins (BSA, lysozyme and myoglobin) and three flavonoids (quercetin, kaempferol and rutin) were analyzed, using three-dimensional fluorescence spectrometry in combination with UV-Vis spectrometry and Fourier transform infrared (FTIR) spectroscopy. The stabilities of unbound flavonoids and protein-bound flavonoids were compared. The correlation between the interaction and stability was analyzed. The results showed that the hydrophobic interaction was the main binding code in all proteins and flavonoids systems. However, the hydrogen bond has been involved merely in the BSA system. The stability of all three flavonoids (quercetin, kaempferol and rutin) was improved by BSA. There was a great correlation between the hydrogen bonding and the stability of the flavonoids in the presence of BSA. It suggested that the protection of BSA on the flavonoids was due to the intermolecular hydrogen bonding between BSA and flavonoid, and the stronger hydrogen bonding resulted in more protection.

Bovine serum albumin nanoparticle promotes the stability of quercetin in simulated intestinal fluid.

Quercetin (Que) is a flavonoid widely distributed in vegetables and fruits and exhibits strong antioxidant activity, but the poor stability of Que limits its function and application. The present study developed a nanoparticle (NP) using bovine serum albumin (BSA) as a matrix to encapsulate Que. The stability of encapsulated Que by BSA NP was tracked in a simulated intestinal fluid (SIF). The antioxidant activity of encapsulated Que was evaluated by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging assays. Furthermore, the stabilizing mechanism of Que by BSA NP was investigated, using scanning transmisson electron microscopy (STEM), dynamic light scattering (DLS), UV-vis, fluorescence spectrometry, and circular dichroism (CD). The results revealed that Que was effectively encapsulated by BSA and formed spherical NP (<10 nm). BSA NP not only promoted the stability of encapsulated Que but also kept the antioxidant activity of encapsulated Que. The driving forces for BSA-Que association were hydrophobic interaction and hydrogen bond, and the latter was involved in the mechanism of Que stabilization. This suggested that BSA NP could be a good carrier to deliver hydrophobic flavonols.