A nanoformulation of cisplatin with arabinoxylan having enhanced activity against hepatocellular carcinoma through upregulation of apoptotic and necroptotic pathways.

Cisplatin is a versatile drug used to treat various types of cancer, but it is associated with high toxicity and resistance problems. Several approaches, including nanotechnology, have been adopted to minimize the toxic effects and to overcome the resistance of cisplatin. Most of the nanoformulations involve the use of synthetic or semisynthetic polymers as drug carriers. In this study arabinoxylan nanoparticles have been investigated as drug reservoirs for intestinal drug delivery. The drug-loaded arabinoxylan nanoparticles (size: ∼1.8 nm, polydispersity index: 0.3 ± 0.04) were prepared and nanoformulation was characterized by various analytical techniques. The nanoformulation was found to be stable (zeta potential: 31.6 ± 1.1 mV). An in vitro cytotoxicity against HepG2 and HEK 293 cell lines was studied. The cell viability analysis showed greater efficacy than the standard cisplatin (IC50: cisplatin 2.4, arabinoxylan nanoformulation 1.3 µg mL-1). The expression profile of carcinogenic markers revealed a six-fold upregulation of MLKL and 0.9-fold down regulation of KRAS, suggesting the activation of the necroptotic pathway by the drug-loaded nanoparticles. The nanoformulation exhibited a sustained release of cisplatin with a cumulative release of ∼40 % (at pH 7.4) and ∼30 % (at pH 5.5) over a period of 12 h with very low initial burst. The study suggests that the use of the new nanoformulation can significantly reduce the required dose of cisplatin without compromising efficacy and more efficient release at basic pH.

Alfalfa-grass mixtures reduce greenhouse gas emissions and net global warming potential while maintaining yield advantages over monocultures.

Improving forage productivity with lower greenhouse gas (GHG) emissions from limited grassland has been a hotspot of interest in global agricultural production. In this study, we analyzed the effects of grasses (tall fescue, smooth bromegrass), legume (alfalfa), and alfalfa-grass (alfalfa + smooth bromegrass and alfalfa + tall fescue) mixtures on GHG emissions, net global warming potential (Net GWP), yield-based greenhouse gas intensity (GHGI), soil chemical properties and forage productivity in cultivated grassland in northwest China during 2020-2021. Our results demonstrated that alfalfa-grass mixtures significantly improved forage productivity. The highest total dry matter yield (DMY) during 2020 and 2021 was obtained from alfalfa-tall fescue (11,311 and 13,338 kg ha-1) and alfalfa-smooth bromegrass mixtures (10,781 and 12,467 kg ha-1). The annual cumulative GHG emissions from mixtures were lower than alfalfa monoculture. Alfalfa-grass mixtures significantly reduced GHGI compared with the grass or alfalfa monocultures. Furthermore, results indicated that grass, alfalfa and alfalfa-grass mixtures differentially affected soil chemical properties. Lower soil pH and C/N ratio were recorded in alfalfa monoculture. Alfalfa and mixtures increased soil organic carbon (SOC) and soil total nitrogen (STN) contents. Importantly, alfalfa-grass mixtures are necessary for improving forage productivity and mitigating the GHG emissions in this region. In conclusion, the alfalfa-tall fescue mixture lowered net GWP and GHGI in cultivated grassland while maintaining high forage productivity. These advanced agricultural practices could contribute to the development of climate-sustainable grassland production in China.

Comparative Transcriptome Analysis Reveals Common and Developmental Stage-Specific Genes That Respond to Low Nitrogen in Maize Leaves.

A growing leaf can be divided into three sections: division zone, elongation zone, and maturation zone. In previous studies, low nitrogen (LN) inhibited maize growth and development, especially leaf growth; however, the gene expression in response to LN in different regions in leaf were not clear. Here, using hydroponics and a transcriptome approach, we systematically analyzed the molecular responses of those zones and differentially expressed genes (DEG) in response to LN supply. Developmental stage-specific genes (SGs) were highly stage-specific and involved in distinct biological processes. SGs from division (SGs-DZ) and elongation zones (SGs-EZ) were more related to developmentally dependent processes, whereas SGs of the maturation zone (SGs-MZ) were more related to metabolic processes. The common genes (CGs) were overrepresented in carbon and N metabolism, suggesting that rebalancing carbon and N metabolism in maize leaves under LN condition was independent of developmental stage. Coexpression modules (CMs) were also constructed in our experiment and a total of eight CMs were detected. Most of SGs-DZ and SGs-EZ were classified into a set termed CM turquoise, which was mainly enriched in ribosome and DNA replication, whereas several genes from SGs-MZ and CGs were clustered into CM blue, which mainly focused on photosynthesis and carbon metabolism. Finally, a comprehensive coexpression network was extracted from CM blue, and several maize CONSTANS-LIKE(ZmCOL) genes seemed to participate in regulating photosynthesis in maize leaves under LN condition in a developmental stage-specific manner. With this study, we uncovered the LN-responsive CGs and SGs that are important for promoting plant growth and development under insufficient nitrogen supply.

Assessing the sensitivity of alfalfa yield potential to climate impact under future scenarios in Iran.

Alfalfa is a major forage crop in Iran. To quantify the impact of climate change on its yield and water application for irrigation in Iran, the SSM-iCrop2 simulation model and two GCMs of IPSL and HadGEM were used under RCP4.5 and RCP8.5 for the 2050s. Despite increased temperatures, alfalfa forage yield will increase in most of the regions across the country due to acceleration of spring regrowth, a higher number of cuttings, increased incident and received photosynthetically active radiation because of increased growing season length due to increased temperatures, and positive effect of CO2 on photosynthesis and radiation use efficiency. Changes in climatic conditions have had a significant impact on alfalfa net irrigation water, and the sum of net irrigation water has a direct relationship with alfalfa yield. Due to increased temperature, changes in rainfall, and improved concentration of atmospheric CO2, the forage yield of alfalfa will fluctuate highly under all climatic scenarios. The highest increase and decrease in the average yield using the HadGEM model under RCP8.5 was 32 and - 33%, respectively. The average net irrigation water of alfalfa increased by 36% in the HadGEM model under RCP8.5 and decreased by - 41% in the IPSL model under RCP8.5. Therefore, to improve alfalfa yield in Iran in the future, strategies compatible such as high temperature-tolerant cultivars may be the most reasonable approaches.

Antibiograms of Gut Flora of Poultry Farms Workers Reveal Higher Resistance Levels as Compared to Non-Workers.

Introduction: Antibiotics are being used in humans and animals for treatment and control of bacterial infections. Excessive use of antibiotics in the production of poultry is a popular practice, but it poses serious health issues by transferring resistance from farm to humans via food or direct exposure. Study Objective: The objective of this study was to carry out a comparison of the resistance and sensitivity profile of isolated isolates from sewage of toilets that were in use of workers inside the farm and from sewage of household toilets. Methodology: In this study, a total of 320 sewage samples were collected. The antibiotic susceptibility profile was checked by Kirby-Bauer disc diffusion method, and the statistical analysis was carried out by MS excel. Chi-square test was performed to determine whether the antibiograms from two sample types were statistically different from each other or not. Results: From 320 sewage samples, a total of 296 bacterial isolates were isolated among which the leading bacterium was E. coli. The proportion of resistance, ESBL production and MDR was significantly higher in bacteria isolated from sewage of toilets under use of poultry farm workers as compared to the sewage from domestic use toilets. Conclusion: Resistance significantly increased in the bacteria isolated from toilets under use of poultry farm workers as compared to the ones isolated from control sewage samples.

A growth and biochemistry of ten high yielding genotypes of Pakistani rice (Oryza sativa L.) at maturity under elevated tropospheric ozone.

Experimental studies were conducted to estimate the possible damage caused to ten rice (Oryza sativa L.) genotypes of Pakistan by tropospheric ozone. The experimental site is located at 31.4504° N and 73.1350° E, at an altitude of 184 m.a.s level with an average annual rainfall of 784 mm. A suitable and agile method was adopted to assess tolerance and susceptibility in rice genotypes at an early growth stage. Genotype Injury response, growth and biochemical parameters were measured to estimate possible effects of ozone, which was subsequently proclaimed as a criterion for ozone tolerance. Rice genotypes were subjected to ozone concentrations of 70 pbb (Current ambient) and 120 pbb (expected in near future) under a polytunnel. The findings indicated that ozone, an atmospheric pollutant, substantially harmed crop growth and metabolism, as well as inflicted a specific type of foliar injury that caused early leaf senescence. Rice genotype IR-9 followed by Punjab-Basmati and Ksk-434 appeared to be the most susceptible, whereas Basmati-515 followed by Basmati 2000 and super-Basmati were found to be Ozone-tolerant. Plant genotypes grown under elevated ozone showed 13.45% and 11.35% reduction in total root and shoot dry weight, and 25.54% and 6.6% decrease in plant leaf area and plant total length respectively compared to the control group. A significant interaction between treatment × chemical components and growth parameters was also found. The Present study confirms a direct relationship between visual response and growth as well as biochemical parameters. Declared results were statistically analyzed by using analysis of variance at confidence level of p < 0.05.

Quantifying climate-induced drought risk to livelihood and mitigation actions in Balochistan.

Climate change-induced disasters show the highest risk for agriculture and livelihoods in rural areas of developing countries. Due to changing rainfall pattern, the arid and semiarid region of Pakistan faces frequent droughts. Farming communities affected by drought disasters are causing serious threats to livelihood, global food crises, environmental migration, and sustainable development. The existing study was designed to quantify two key components through (1) analysis of agrometeorological data (1981-2017) with exploratory data analysis and Mann-Kendall trend analysis; (2) extensive field survey (200 households). The multivariate probit model has been run to detect determinants of coping and adaptive strategies by farmers. Our results showed that the farmers supposed that temperature and rainfall were highly fluctuating in recent years equally. Farmers adopted different coping and adaptive measures that include crop diversification, input adjustment, water management, asset depletion, income diversification, and migration to sustain their livelihood during stress periods. The agrometeorological data analysis revealed that the agricultural vulnerability to drought risks increased significantly, and the survey results projected that 64.7% of the population is exposed to drought directly or indirectly. Sen's slope quantification resulted in (0.025 °C) rise in temperature, (- 2.936 mm) decline in rainfall year-1. Modeling future scenarios resulted in an increase in temperature up to 0.7 °C, 1.2 °C, and a decrease in precipitation up to 161.48 mm, 103.5 mm in 2040 and 2060. The study evaluated a huge gap in the provision of drought risk resilience services, crop insurance, and climate-smart training practices to build capacities among farmers to cope with the impacts of extreme weather conditions. Our research might provide the groundwork to upgrade actions to drought prevention and early warning in water scarcity areas. Supplementary Information: The online version contains supplementary material available at 10.1007/s11069-021-04913-4.

The Berlin principles on one health - Bridging global health and conservation.

For over 15-years, proponents of the One Health approach have worked to consistently interweave components that should never have been separated and now more than ever need to be re-connected: the health of humans, non-human animals, and ecosystems. We have failed to heed the warning signs. A One Health approach is paramount in directing our future health in this acutely and irrevocably changed world. COVID-19 has shown us the exorbitant cost of inaction. The time to act is now.

Elevated Soluble Galectin-3 as a Marker of Chemotherapy Efficacy in Breast Cancer Patients: A Prospective Study.

PURPOSE: Galectin-3 (Gal-3) is a glycan-binding lectin with a debated role in cancer progression due to its various functions and patterns of expression. The current study investigates the relationship between breast cancer prognosis and secreted Gal-3. METHODS: Breast cancer patients with first time cancer diagnosis and no prior treatment (n = 88) were placed in either adjuvant or neoadjuvant setting based on their treatment modality. Stromal and plasma Gal-3 levels were measured in each patient at the time of diagnosis and then throughout treatment using immunohistochemistry (IHC) and ELISA, respectively. Healthy women (>18 years of age, n = 63) were used to establish baseline levels of plasma Gal-3. Patients were followed for 84 months for disease-free survival analysis. RESULTS: Enhanced levels of plasma (adjuvant) and stromal (neoadjuvant) Gal-3 were found to be markers of chemotherapy efficacy. The patients with chemotherapy-induced increase in extracellular Gal-3 had longer disease-free interval and significantly lower rate of recurrence during 84-month follow-up compared to patients with unchanged or decreased secretion. CONCLUSION: The findings support the use of plasma Gal-3 as a marker for chemotherapy efficacy when no residual tumor is visible through imaging. Furthermore, stromal levels in any remaining tumors postchemotherapy can also be used to predict long-term prognosis in patients.

Urban expansion in the Atlantic Forest: applying the Nature Futures Framework to develop a conceptual model and future scenarios / Expansão urbana na Mata Atlântica: aplicando o Nature Futures Framework para desenvolver um modelo conceitual e cenários futuros

Abstract: The Atlantic Forest is an important hotspot of biodiversity and ecosystem services that contributes to the well-being of its 125 million human inhabitants, about three quarters of the Brazilian population. In the coming decades, forecasts show that urban areas in the Atlantic Forest will grow at the expense of natural ecosystems, leading to increasing pressure on biodiversity and ecosystem services. We used the Nature Futures Framework (NFF) for envisioning positive scenarios for cities in the Atlantic Forest. First, we developed a conceptual model based on the Driver-Pressure-State-Impact-Response (DPSIR) approach to describe consequences of urban growth for the three NFF perspectives: Nature for Society, Nature for Nature and Nature as Culture. Second, we proposed scenario storylines that encompass multiple social-ecological values of nature and could be used by policy makers to plan desirable futures for the Atlantic Forest. Then, we discussed the impact of distinct policies on these values, identifying the different ways in which the management of urban green and blue spaces, natural ecosystems, and urban densities can lead to different social-ecological outcomes. We further detail the complexity, trade-offs, and synergies regarding city development, nature conservation, and human well-being in this tropical hotspot. Applying NFF can contribute to the ongoing debate regarding urban sustainability, by providing an interdisciplinary and integrative approach that explicitly incorporates multiple values of nature and the visualization of positive futures.

Resumo: A Mata Atlântica é um importante hotspot de biodiversidade e serviços ecossistêmicos que contribui para o bem-estar de seus 125 milhões de habitantes, cerca de três quartos da população brasileira. Nas próximas décadas, a previsão é de que as áreas urbanas na Mata Atlântica crescerão às custas de ecossistemas naturais, conduzindo a um aumento na pressão sobre a biodiversidade e os serviços ecossistêmicos. Nós usamos a perspectiva do Nature Futures Framework (NFF) para visualizar cenários positivos para as cidades na Mata Atlântica. Em primeiro lugar, desenvolvemos um modelo conceitual baseado na abordagem Driver-Pressure-State-Impact-Response (DPSIR) para descrever as consequências do crescimento urbano para as três perspectivas do NFF: Natureza para a Sociedade, Natureza para a Natureza, e Natureza como Cultura. Em seguida, propusemos cenários na forma de narrativas que abrangem múltiplos valores socioecológicos para a natureza, e que pudessem ser usados por tomadores de decisão para planejar futuros desejáveis para a Mata Atlântica. Posteriormente, discutimos os impactos de distintas políticas sob esses valores, identificando como diferentes maneiras de gerenciar os espaços urbanos verdes e azuis, os ecossistemas naturais, e as densidades urbanas podem conduzir a diferentes contextos socioecológicos. Ainda, nós detalhamos a complexidade, os trade-offs e as sinergias relacionados ao desenvolvimento de cidades, conservação da natureza e bem-estar humano neste hotspot tropical. A aplicação do NFF pode contribuir para o debate em andamento sobre sustentabilidade urbana, por meio do fornecimento de uma abordagem interdisciplinar e integrativa que explicitamente incorpora múltiplos valores da natureza e a visualização de futuros positivos.

Simultaneous irradiation of fibroblasts and carcinoma cells repress the secretion of soluble factors able to stimulate carcinoma cell migration.

Stroma mediated wound healing signals may share similarities with the ones produced by tumor's microenvironment and their modulation may impact tumor response to the various anti-cancer treatments including radiation therapy. Therefore we conducted this study, to assess the crosstalk between stromal and carcinoma cells in response to radiotherapy by genetic modulation of the stroma and irradiation. We found that fibroblasts irrespective of their RhoB status do not modulate intrinsic radiosensitivity of TC-1 but produce diffusible factors able to modify tumor cell fate. Then we found that Wt and RhoB deficient fibroblasts stimulated TC-1 migration through distinct mechanisms which are TGF-ß1 and MMP-mediated respectively. Lastly, we found that simultaneous irradiation of fibroblasts and TC-1 abrogated the pro-migratory phenotype by repression of TGF-ß and MMP secretion. This last result is highly relevant to the clinical situation and suggests that conversely to, the current view; irradiated stroma would not enhance carcinoma migration and could be manipulated to promote anti-tumor immune response.