Identification of novel and safe fungicidal molecules against fusarium oxysporum from plant essential oils: in vitro and computational approaches.

Phytopathogenic fungi are serious threats in the agriculture sector especially in fruit and vegetable production. The use of plant essential oil as antifungal agents has been in practice from many years. Plant essential oils (PEOs) of Cuminum cyminum, Trachyspermum ammi, Azadirachta indica, Syzygium aromaticum, Moringa oleifera, Mentha spicata, Eucalyptus grandis, Allium sativum, and Citrus sinensis were tested against Fusarium oxysporum. Three phase trials consist of lab testing (MIC and MFC), field testing (seed treatment and foliar spray), and computer-aided fungicide design (CAFD). Two concentrations (25 and 50 μl/ml) have been used to asses MIC while MFC was assessed at four concentrations (25, 50, 75, and 100 μl/ml). C. sinensis showed the largest inhibition zone (47.5 and 46.3 m2) for both concentrations. The lowest disease incidence and disease severity were recorded in treatments with C. sinensis PEO. Citrus sinensis that qualified in laboratory and field trials was selected for CAFD. The chemical compounds of C. sinensis PEO were docked with polyketide synthase beta-ketoacyl synthase domain of F. oxysporum by AutoDock Vina. The best docked complex was formed by nootkatone with -6.0 kcal/mol binding affinity. Pharmacophore of the top seven C. sinensis PEO compounds was used for merged pharmacophore generation. The best pharmacophore model with 0.8492 score was screened against the CMNP database. Top hit compounds from screening were selected and docked with polyketide synthase beta-ketoacyl synthase domain. Four compounds with the highest binding affinity and hydrogen bonding were selected for confirmation of lead molecule by doing MD simulation. The polyketide synthase-CMNPD24498 showed the highest stability throughout 80 ns run of MD simulation. CMNPD24498 (FW054-1) from Verrucosispora was selected as the lead compound against F. oxysporum

Chemical characterization, antioxidant and antimicrobial activities of essential oil from <em>Melaleuca quinquenervia</em> leaves

686-693Niaouli oil is an essential oil known for its applications in aromatherapy and pharmaceutical preparations for coughs, colds, rheumatism and neuralgia. It also serves as a sedative, possesses antifungal activity, and used in perfume industry. Melaleuca quinquenervia (Cav.) S.T. Blake, commonly called, paper bark tea tree or punk tree, is a potential source of niaouli oil. Here, we analyzed the chemical composition of essential oil from M. quinquenervia leaves and evaluated its antioxidant and antimicrobial potential. Chemical analysis of the oil by GC-FID and GC-MS revealed 1,8-cineole (31.0%) as a major component followed by p-cymen-8-ol (19.7%), p-cymene (16.5%), α-terpineol (9.9%), limonene (6.8%), α-pinene (4.2%) and terpinolene (4.2%). M. quinquenervia essential oil demonstrated good antioxidant activity by inhibiting 84.3 % of 2,2׳-diphenyl-1-picrylhydrazyl radical and ferric reducing power (1.94±0.007) at 100 µg/mL. Further, it was highly effective against tested food borne bacterial as well as fungal pathogens inducing 11.0-46.0 mm and 11.8-46.0 mm zones of inhibition, respectively at concentration of 8-250 μg/mL. The high degrees of antibacterial and antifungal activities were further confirmed at 8 μg/mL minimum bactericidal concentrations and minimum fungicidal concentrations, respectively. Time kill assay showed significant bactericidal and fungicidal effects of essential oil for four weeks. The high antimicrobial and antioxidant activities of M. quinquenervia essential oil substantiate its potential use as alternative to chemical preservatives in food industry

Automatic COVID-19 Lung Infection Segmentation through Modified Unet Model

The coronavirus (COVID-19) pandemic has had a terrible impact on human lives globally, with far-reaching consequences for the health and well-being of many people around the world. Statistically, 305.9 million people worldwide tested positive for COVID-19, and 5.48 million people died due to COVID-19 up to 10 January 2022. CT scans can be used as an alternative to time-consuming RT-PCR testing for COVID-19. This research work proposes a segmentation approach to identifying ground glass opacity or ROI in CT images developed by coronavirus, with a modified structure of the Unet model having been used to classify the region of interest at the pixel level. The problem with segmentation is that the GGO often appears indistinguishable from a healthy lung in the initial stages of COVID-19, and so, to cope with this, the increased set of weights in contracting and expanding the Unet path and an improved convolutional module is added in order to establish the connection between the encoder and decoder pipeline. This has a major capacity to segment the GGO in the case of COVID-19, with the proposed model being referred to as "convUnet." The experiment was performed on the Medseg1 dataset, and the addition of a set of weights at each layer of the model and modification in the connected module in Unet led to an improvement in overall segmentation results. The quantitative results obtained using accuracy, recall, precision, dice-coefficient, F1score, and IOU were 93.29%, 93.01%, 93.67%, 92.46%, 93.34%, 86.96%, respectively, which is better than that obtained using Unet and other state-of-the-art models. Therefore, this segmentation approach proved to be more accurate, fast, and reliable in helping doctors to diagnose COVID-19 quickly and efficiently

A slight variability in anthropometric parameters but a significant delay in sexual maturation rating and decreased hormonal parameters in patients with delayed puberty

Objectives: The present study was designed to compare anthropometric parameters, sexual maturation rating (SMR) and plasma follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone (T) levels in male delayed puberty patients and age matched healthy controls and determine whether a difference exists between these parameters before and after 18 years of age in delayed puberty patients. Methodology: Anthropometric parameters (height, weight, body mass index (BMI), bone age), SMR (penile length, testicular volume, pubic and facial hair stage) and plasma concentrations of FSH, LH and T were determined through respective ELISA in 37 sporadic delayed puberty male patients of 14-23 years and 55 age matched controls visiting Shifa International Hospitals Ltd., Islamabad, Pakistan Institute of Medical Sciences, Islamabad and Military Hospital, Rawalpindi, Pakistan. Data were interpreted using Student’s t-test and ANOVA. Results: The height of delayed puberty patients was lower than controls from 14-17 years, whereas weight of delayed puberty patients was slightly more than controls from 17-23 years; most of patients were in over-weight category. Bone age of most of patients was slightly delayed than chronological age.&nbsp

Cyclophosphazene Intrinsically Derived Heteroatom (S, N, P, O)-Doped Carbon Nanoplates for Ultrasensitive Monitoring of Dopamine from Chicken Samples

A novel, metal-free electrode based on heteroatom (S, N, P, O)-doped carbon nanoplates (SNPO-CPL) modifying lead pencil graphite (LPG) has been synthesized by carbonizing a unique heteroatom (S, N, P, O)-containing novel polymer, poly(cyclcotriphosphazene-co-2,5-dioxy-1,4-dithiane) (PCD), for precise screening of dopamine (DA). The designed electrode, SNPO-CPL-800, with optimized percentage of S, N, P, O doping through the sp2-carbon chain, and a large number of surface defects (thus leading to a maximum exposition number of catalytic active sites) led to fast molecular diffusion through the micro-porous structure and facilitated strong binding interaction with the targeted molecules in the interactive signaling transducer at the electrode&ndash;electrolyte interface. The designed SNPO-CPL-800 electrode exhibited a sensitive and selective response towards DA monitoring, with a limit of detection (LOD) of 0.01 nM. We also monitored DA levels in commercially available chicken samples using the SNPO-CPL-800 electrode even in the presence of interfering species, thus proving the effectiveness of the designed electrode for the precise monitoring of DA in real samples. This research shows there is a strong potential for opening new windows for ultrasensitive DA monitoring with metal-free electrodes

A Slight Variability in Anthropometric Parameters But A Significant Delay in Sexual Maturation Rating and Decreased Hormonal Parameters in Patients with Delayed Puberty

Objectives: The present study was designed to compare anthropometric parameters, sexual maturation rating (SMR) and plasma follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone (T) levels in male delayed puberty patients and age matched healthy controls and determine whether a difference exists between these parameters before and after 18 years of age in delayed puberty patients. Methodology: Anthropometric parameters (height, weight, body mass index (BMI), bone age), SMR (penile length, testicular volume, pubic and facial hair stage) and plasma concentrations of FSH, LH and T were determined through respective ELISA in 37 sporadic delayed puberty male patients of 14-23 years and 55 age matched controls visiting Shifa International Hospitals Ltd., Islamabad, Pakistan Institute of Medical Sciences, Islamabad and Military Hospital, Rawalpindi, Pakistan. Data were interpreted using Student's t-test and ANOVA. Results: The height of delayed puberty patients was lower than controls from 14-17 years, whereas weight of delayed puberty patients was slightly more than controls from 17-23 years; most of patients were in over-weight category. Bone age of most of patients was slightly delayed than chronological age.&nbsp

The formation of complex acetylcholine receptor clusters requires MuSK kinase activity and structural information from the MuSK extracellular domain

Efficient synaptic transmission at the neuromuscular junction (NMJ) requires the topological maturation of the postsynaptic apparatus from an oval acetylcholine receptor (AChR)-rich plaque into a complex pretzel-shaped array of branches. However, compared to NMJ formation very little is known about the mechanisms that regulate NMJ maturation. Recently the process of in vivo transformation from plaque into pretzel has been reproduced in vitro by culturing myotubes aneurally on laminin-coated substrate. It was proposed that the formation of complex AChR clusters is regulated by a MuSK-dependent muscle intrinsic program. To elucidate the structure–function role of MuSK in the aneural maturation of AChR pretzels, we used muscle cell lines expressing MuSK mutant and chimeric proteins. Here we report, that besides its role during agrin-induced AChR clustering, MuSK kinase activity is also necessary for substrate-dependent cluster formation. Constitutive-active MuSK induces larger AChR clusters, a faster cluster maturation on laminin and increases the anchorage of AChRs to the cytoskeleton compared to MuSK wild-type. In addition, we find that the juxtamembrane region of MuSK, which has previously been shown to regulate agrin-induced AChR clustering, is unable to induce complex AChR clusters on laminin substrate. Most interestingly, MuSK kinase activity is not sufficient for laminin-dependent AChR cluster formation since the MuSK ectodomain is also required suggesting a so far undiscovered instructive role for the extracellular domain of MuSK

Safeguarding human health in the Anthropocene epoch: report of The Rockefeller Foundation-Lancet Commission on planetary health.

Earth's natural systems represent a growing threat to human health. And yet, global health has mainly improved as these changes have gathered pace. What is the explanation? As a Commission, we are deeply concerned that the explanation is straightforward and sobering: we have been mortgaging the health of future generations to realise economic and development gains in the present. By unsustainably exploiting nature's resources, human civilisation has fl ourished but now risks substantial health eff ects from the degradation of nature's life support systems in the future. Health eff ects from changes to the environment including climatic change, ocean acidifi cation, land degradation, water scarcity, overexploitation of fi sheries, and biodiversity loss pose serious challenges to the global health gains of the past several decades and are likely to become increasingly dominant during the second half of this century and beyond. These striking trends are driven by highly inequitable, ineffi cient, and unsustainable patterns of resource consumption and technological development, together with population growth. We identify three categories of challenges that have to be addressed to maintain and enhance human health in the face of increasingly harmful environmental trends. Firstly, conceptual and empathy failures (imagination challenges), such as an over-reliance on gross domestic product as a measure of human progress, the failure to account for future health and environmental harms over present day gains, and the disproportionate eff ect of those harms on the poor and those in developing nations. Secondly, knowledge failures (research and information challenges), such as failure to address social and environmental drivers of ill health, a historical scarcity of transdisciplinary research and funding, together with an unwillingness or inability to deal with uncertainty within decision making frameworks. Thirdly, implementation failures (governance challenges), such as how governments and institutions delay recognition and responses to threats, especially when faced with uncertainties, pooled common resources, and time lags between action and eff ect. Although better evidence is needed to underpin appropriate policies than is available at present, this should not be used as an excuse for inaction. Substantial potential exists to link action to reduce environmental damage with improved health outcomes for nations at all levels of economic development. This Commission identifi es opportunities for action by six key constituencies: health professionals, research funders and the academic community, the UN and Bretton Woods bodies, governments, investors and corporate reporting bodies, and civil society organisations. Depreciation of natural capital and nature's subsidy should be accounted for so that economy and nature are not falsely separated. Policies should balance social progress, environmental sustainability, and the economy. To support a world population of 9-10 billion people or more, resilient food and agricultural systems are needed to address both undernutrition and overnutrition, reduce waste, diversify diets, and minimise environmental damage. Meeting the need for modern family planning can improve health in the short termeg, from reduced maternal mortality and reduced pressures on the environment and on infrastructure. Planetary health off ers an unprecedented opportunity for advocacy of global and national reforms of taxes and subsidies for many sectors of the economy, including energy, agriculture, water, fi sheries, and health. Regional trade treaties should act to further incorporate the protection of health in the near and long term. Several essential steps need to be taken to transform the economy to support planetary health. These steps include a reduction of waste through the creation of products that are more durable and require less energy and materials to manufacture than those often produced at present; the incentivisation of recycling, reuse, and repair; and the substitution of hazardous materials with safer alternatives. Despite present limitations, the Sustainable Development Goals provide a great opportunity to integrate health and sustainability through the judicious selection of relevant indicators relevant to human wellbeing, the enabling infrastructure for development, and the supporting natural systems, together with the need for strong governance. The landscape, ecosystems, and the biodiversity they contain can be managed to protect natural systems, and indirectly, reduce human disease risk. Intact and restored ecosystems can contribute to resilience (see panel 1 for glossary of terms used in this report), for example, through improved coastal protection (eg, through wave attenuation) and the ability of fl oodplains and greening of river catchments to protect from river fl ooding events by diverting and holding excess water. The growth in urban populations emphasises the importance of policies to improve health and the urban environment, such as through reduced air pollution, increased physical activity, provision of green space, and urban planning to prevent sprawl and decrease the magnitude of urban heat islands. Transdisciplinary research activities and capacity need substantial and urgent expansion. Present research limitations should not delay action. In situations where technology and knowledge can deliver win-win solutions and co-benefi ts, rapid scale-up can be achieved if researchers move ahead and assess the implementation of potential solutions. Recent scientifi c investments towards understanding non-linear state shifts in ecosystems are very important, but in the absence of improved understanding and predictability of such changes, eff orts to improve resilience for human health and adaptation strategies remain a priority. The creation of integrated surveillance systems that collect rigorous health, socioeconomic, and environmental data for defi ned populations over long time periods can provide early detection of emerging disease outbreaks or changes in nutrition and non-communicable disease burden. The improvement of risk communication to policy makers and the public and the support of policy makers to make evidence-informed decisions can be helped by an increased capacity to do systematic reviews and the provision of rigorous policy briefs. Health professionals have an essential role in the achievement of planetary health: working across sectors to integrate policies that advance health and environmental sustainability, tackling health inequities, reducing the environmental impacts of health systems, and increasing the resilience of health systems and populations to environmental change. Humanity can be stewarded successfully through the 21st century by addressing the unacceptable inequities in health and wealth within the environmental limits of the Earth, but this will require the generation of new knowledge, implementation of wise policies, decisive action, and inspirational leadership