Templepitts7901

High levels of reactive oxygen species (ROS) in tumors have been shown to exert anti-tumor activity, leading to the concept of ROS induction as therapeutic strategy. The organometallic compound ferrocene (Fc) generates ROS through a reversible one-electron oxidation. Incorporation of Fc into a tumor-targeting, bioactive molecule can enhance its therapeutic activity and enable tumor specific delivery. Therefore, we conjugated Fc to five synthetic, Arg-Gly-Asp (RGD)-based integrin binding ligands to enable targeting of the cell adhesion and signaling receptor integrin subtypes αvβ3, α5β1, or αvβ6, which are overexpressed in various, distinct tumors. We designed and synthesized a library of integrin-ligand-ferrocene (ILF) derivatives and showed that ILF conjugates maintained the high integrin affinity and selectivity of their parent ligands. STSinhibitor A thorough biological characterization allowed us to identify the two most promising ligands, an αvβ3 (L2b) and an αvβ6 (L3b) targeting ILF, which displayed selective integrin-dependent cell uptake and pronounced ferrocene-mediated anti-tumor effects in vitro, along with increased ROS production and DNA damage. Hence, ILFs are promising candidates for the selective, tumor-targeted delivery of ferrocene to maximize its anti-cancer efficacy and minimize systemic toxicity, thereby improving the therapeutic window of ferrocene compared to currently used non-selective anti-cancer drugs.Afforestation/reforestation (A/R) programs spearheaded by Civil Society Organizations (CSOs) play a significant role in reaching global climate policy targets and helping low-income nations meet the United Nations (UN) Sustainable Development Goals (SDGs). However, these organizations face unprecedented challenges due to the COVID-19 pandemic. Consequently, these challenges affect their ability to address issues associated with deforestation and forest degradation in a timely manner. We discuss the influence COVID-19 can have on previous, present and future A/R initiatives, in particular, the ones led by International Non-governmental Organizations (INGOs). We provide thirty-three recommendations for exploring underlying deforestation patterns and optimizing forest policy reforms to support forest cover expansion during the pandemic. The recommendations are classified into four groups - i) curbing deforestation and improving A/R, ii) protecting the environment and mitigating climate change, iii) enhancing socio-economic conditions, and iv) amending policy and law enforcement practices.The shorelines frequently suffer adverse impacts from oil spill accidents. As one important technique of shoreline cleanup, the application of surface washing agents (SWAs) can help achieve high oil removal from shoreline substrates with less damage to affected zone. In this study, a framework for evaluation and selection of SWAs in oil spill incidents was constructed to better understand and apply this technique. A decision tree was firstly developed to illustrate all possible scenarios which are appropriate to use SWAs in consideration of oil collectability, shoreline character, types and amount of stranded oil, and cleanup requirement. Based on literature review, theoretical modeling, and experts' suggestions, an integrated multi-criteria decision analysis (MCDA) method was then come up to select the most preferred SWA from five aspects of toxicity, effectiveness, minimal dispersion, demonstrated field test, and cost. Its suitability and rationality were proved by a hypothetical case. In addition, sensitivity analysis was performed by changing the weight of each criterion independently to check the priority rank of alternatives, and it also verified the robustness and stability of this model. The presented framework has significant implications for future research and application of SWAs in the shoreline cleanup.As the largest consumer of rapeseed oil in the world, China should consider the environmental effect of rapeseed oil production. However, only a few improvement measures have been proposed. To fill this gap, this study analyzed the energy, carbon and water footprints of rapeseed oil production based on the International Organization for Standardization standards using the framework of life cycle assessment. Results show that most of the energy, carbon, and water footprint of rapeseed oil production can be contributed to the direct processes of rapeseed cultivation, and the indirect processes of transport and fertilizer/diesel production. The value of energy and carbon footprints are calculated as 726.07 kg oil eq and 3889.75 kg CO2 eq, respectively. For the water footprint, the values of acidification, aquatic eutrophication, carcinogens, freshwater ecotoxicity, water scarcity, and non-carcinogens are 14.24 kg SO2 eq, 4.53 kg PO4-3 eq, 6.72 × 10-5Case, 5.43 × 104 PAF.m3.d, 437.62 m3 deprived, and 1.88 × 10-5 case, respectively. Spatial analysis shows that the total environmental impacts of rapeseed production are concentrated in Sichuan, Hunan, Hubei, and Jiangxi Provinces. Correlation analysis reveals the positive correlation of human health and ecosystem quality with fertilizer application and pesticide loss. In general, the environmental effect can be effectively reduced by adjusting the industrial layout to shorten the distance of transport, improve the fine cultivation degree in low-yield areas, and decrease the use of pesticides in the hilly region of southern China.

and Purpose Postnatal progressive microcephaly, with seizures and brain atrophy (OMIM # 613668) is a rare disorder caused by a homozygous founder missense mutation c.1112T>C (p.L371P) in the MED17 gene on chromosome 11 that was identified in 2010 in Caucasus Jewish families. The present study aimed to delineate the phenotype and developmental outcomes in patients diagnosed with this mutation to date.

We conducted a medical charts review to collect the clinical, laboratory and neuroimaging findings in patients from several unrelated families of Caucasus-Jewish origin, who were diagnosed with the same homozygous c.1112T>C MED17 mutation.

The study cohort, including the previously reported patients, comprised 10 males and 5 females from 11 families. All subjects had at birth a normal head circumference, which steeply declined to -6SD within a few months. None of the patients achieved developmental milestones. All patients had progressive spasticity and were wheelchair bound due to spastic quadriplegia.