Bending the curve of terrestrial biodiversity needs an integrated strategy Summary paragraph Increased efforts are required to prevent further losses of terrestrial biodiversity and the ecosystem services it provides 1,2. Ambitious targets have been proposed, such as reversing the declining trends in biodiversity 3-yet, just feeding the growing human population will make this a challenge 4. We use an ensemble of land-use and biodiversity models to assess whether (and if so, how) humanity can reverse terrestrial biodiversity declines due to habitat conversion, a major threat to biodiversity 5. We show that immediate efforts, consistent with the broader sustainability agenda but of unprecedented ambition and coordination, may allow to feed the growing human population while reversing global terrestrial biodiversity trends from habitat conversion. If we decide to increase the extent of land under conservation management, restore degraded land, and generalize landscapelevel conservation planning, biodiversity trends from habitat conversion could become positive by mid-century on average across models (confidence interval: 2042-2061), but not for all models. Food prices could increase and, on average across models, almost half (confidence interval: 34-50%) of future biodiversity losses could not be avoided. However, additionally tackling the drivers of landuse change may avoid conflict with affordable food provision and reduces the food system's environmental impacts. Through further sustainable intensification and trade, reduced food waste, and healthier human diets, more than two thirds of future biodiversity losses are avoided and the biodiversity trends from habitat conversion are reversed by 2050 for almost all models. Although limiting further loss will remain challenging in several biodiversity-rich regions, and other threats, such as climate change, must be addressed to truly reverse biodiversity declines, our results show that bold conservation efforts and food system transformation are central to an effective post-2020 biodiversity strategy. Reversing biodiversity trends by 2050 Without further efforts to counteract habitat loss and degradation, we projected that global biodiversity will continue to decline (BASE scenario; Fig. 1). Rates of loss over time for all nine BDIs in 2010-2050 were close to or greater than those estimated for 1970-2010 (Extended data Extended Data Table 1). For various biodiversity aspects, on average across IAM and BDI combinations, peak losses over the 2010-2100 period were: 13% (range: 1-26%) for the extent of suitable habitat, 54% (range: 45-63%) for wildlife population density, 5% (range: 2-9%) for local compositional intactness , 4% (range: 1-12%) for global extinctions, and 4% (range: 2-8%) for regional extinctions (Extended Data Table 1). Percentage losses were greatest in biodiversity-rich regions (Sub-Saharan Africa, South Asia, South East Asia, the Caribbean and Latin America; Extended Data Fig. 2). The projected future trends for habitat loss and degradation and its driv...

Spatial autocorrelation and hot-spot analysis may serve as efficient tools to detect space-time clusters and geospatial hot spots of TB incidence. Between 2005 and 2009, TB incidence in Beijing showed population density and mobility-dependent and eco-social status-dependent space-time clusters and geospatial hot spots.

Background: Specific targeting ability and good cell penetration are two critical requirements of tumor-targeted delivery systems. In the present work, we developed a novel matrix metalloprotein-triggered, cell-penetrating, peptide-modified, star-shaped nanoparticle (NP) based on a functionalized copolymer (MePEG-Peptide-Tri-CL), with the peptide composed of GPLGIAG (matrix metalloprotein-triggered peptide for targeted delivery) and r9 (cell-penetrating peptide for penetration improvement) to enhance its biological specificity and therapeutic effect. Results: Based on the in vitro release study, a sustained release profile was achieved for curcumin (Cur) release from the Cur-P-NPs at pH 7.4. Furthermore, the release rate of Cur was accelerated in the enzymatic reaction. MTT assay results indicated that the biocompatibility of polymer NPs (P-NPs) was inversely related to the NP concentration, while the efficiency toward tumor cell inhibition was positively related to the Cur-P-NP concentration. In addition, Cur-P-NPs showed higher fluorescence intensity than Cur-NPs in tumor cells, indicating improved penetration of tumor cells. An in vivo biodistribution study further demonstrated that Cur-P-NPs exhibited stronger targeting to A549 xenografts than to normal tissue. Furthermore, the strongest tumor growth inhibition (76.95%) was observed in Cur-P-NP-treated A549 tumor xenograft nude mice, with slight pulmonary toxicity. Conclusion: All results demonstrated that Cur-P-NP is a promising drug delivery system that possesses specific enzyme responsiveness for use in anti-tumor therapy.

BackgroundHypoxia plays an important role in vascular remodeling and directly affects vascular smooth muscle cells (VSMC) functions. Macrophage migration inhibitory factor (MIF) is a well known proinflammatory factor, and recent evidence suggests an important role of MIF in the progression of atherosclerosis and restenosis. However, the potential link between hypoxia and MIF in VSMC has not been investigated. The current study was designed to test whether hypoxia could regulate MIF expression in human VSMC. The effect of modulating MIF expression on hypoxia-induced VSMC proliferation and migration was also investigated at the same time.ResultsExpression of MIF mRNA and protein was up-regulated as early as 2 hours in cultured human VSMCs after exposed to moderate hypoxia condition (3% O2). The up-regulation of MIF expression appears to be dependent on hypoxia-inducible transcription factor-1α(HIF-1α) since knockdown of HIF-1α inhibits the hypoxia induction of MIF gene and protein expression. The hypoxia induced expression of MIF was attenuated by antioxidant treatment as well as by inhibition of extracellular signal-regulated kinase (ERK). Under moderate hypoxia conditions (3% O2), both cell proliferation and cell migration were increased in VSMC cells. Blocking the MIF by specific small interference RNA to MIF (MIF-shRNA) resulted in the suppression of proliferation and migration of VSMCs.ConclusionOur results demonstrated that in VSMCs, hypoxia increased MIF gene expression and protein production. The hypoxia-induced HIF-1α activation, reactive oxygen species (ROS) generation and ERK activation might be involved in this response. Both MIF and HIF-1α mediated the hypoxia response of vascular smooth muscle cells, including cell migration and proliferation.

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BackgroundAtherosclerosis is now recognized as a chronic inflammatory disease. Angiotensin II (Ang II) is a critical factor in inflammatory responses, which promotes the pathogenesis of atherosclerosis. Placental growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family cytokines and is associated with inflammatory progress of atherosclerosis. However, the potential link between PlGF and Ang II has not been investigated. In the current study, whether Ang II could regulate PlGF expression, and the effect of PlGF on cell proliferation, was investigated in human vascular endothelial cells (VECs) and smooth muscle cells (VSMCs).ResultsIn growth-arrested human VECs and VSMCs, Ang II induced PlGF mRNA expression after 4 hour treatment, and peaked at 24 hours. 10-6 mol/L Ang II increased PlGF protein production after 8 hour treatment, and peaked at 24 hours. Stimulation with Ang II also induced mRNA expression of VEGF receptor-1 and -2(VEGFR-1 and -2) in these cells. The Ang II type I receptor (AT1R) antagonist blocked Ang II-induced PlGF gene expression and protein production. Several intracellular signals elicited by Ang II were involved in PlGF synthesis, including activation of protein kinase C, extracellular signal-regulated kinase 1/2 (ERK1/2) and PI3-kinase. A neutralizing antibody against PlGF partially inhibited the Ang II-induced proliferation of VECs and VSMCs. However, this antibody showed little effect on the basal proliferation in these cells, whereas blocking antibody of VEGF could suppress both basal and Ang II-induced proliferation in VECs and VSMCs.ConclusionOur results showed for the first time that Ang II could induce the gene expression and protein production of PlGF in VECs and VSMCs, which might play an important role in the pathogenesis of vascular inflammation and atherosclerosis.

Summary.  Background: Increased homocysteine levels in blood might be an important risk factor for the development of cardiovascular diseases. Connective tissue growth factor (CTGF) was found to be involved in atherosclerotic plaque progression. So far, the possible connection between homocysteine and CTGF has not been studied. Objective: This study was designed to test whether homocysteine could induce CTGF expression in vascular smooth muscle cells (VSMC). Methods and results: Hyperhomocysteinemia was induced in Sprague–Dawley rats after 4 weeks of a high‐methionine diet. CTGF mRNA and protein expression was detected in the aortas isolated from hyperhomocysteinemic rats, but not in the controls. The underlying mechanism of homocysteine‐induced CTGF expression was investigated in cultured human umbilical vein smooth muscle cells (HUVSMC). CTGF mRNA expression was induced after treatment with dl‐homocysteine (50 μmol L−1) for 1 h, which remained at the elevated level for up to 8 h. CTGF protein level increased after homocysteine treatment for 8 h, and the elevated status was maintained for up to 48 h. Several intracellular signals elicited by homocysteine are involved in CTGF synthesis, including protein kinase C (PKC) activation and reactive oxygen species (ROS). Transfection HUVSMCs with a CTGF small interference RNA (siRNA) plasmid, which specifically inhibited the expression of CTGF, decreased extracellular matrix (ECM) accumulation caused by homocysteine. Conclusion: Our results demonstrate that homocysteine could increase the expression of CTGF in VSMC both in vivo and in vitro. The novel findings suggest that homocysteine might contribute to accelerated progression of atherosclerotic lesions by inducing CTGF expression.

Reporting on brucellosis, a relatively rare infectious disease caused by Brucella, is often delayed or incomplete in traditional disease surveillance systems in china. internet search engine data related to brucellosis can provide an economical and efficient complement to a conventional surveillance system because people tend to seek brucellosis-related health information from Baidu, the largest search engine in china. in this study, brucellosis incidence data reported by the cDc of china and Baidu index data were gathered to evaluate the relationship between them. We applied an autoregressive integrated moving average (ARiMA) model and an ARiMA model with Baidu search index data as the external variable (ARiMAX) to predict the incidence of brucellosis. the two models based on brucellosis incidence data were then compared, and the ARiMAX model performed better in all the measurements we applied. our results illustrate that Baidu index data can enhance the traditional surveillance system to monitor and predict brucellosis epidemics in china.