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Sustainable development goals (SDGs) adopted in 2015 are geared toward sustainable development through various pathways, one being reducing inequality as covered in SDG 10. Inequalities are a threat to health and wellbeing of populations and a planet Earth in which we live. This rapid review aims to identify key issues that are likely to exacerbate inequalities around the six SDGs directly related to One Health, which are SDG 3, 6, 11, 13, 14 and 15, and suggest some actions that may help to address them using inclusive governance taking into account the coronavirus disease of 2019 (COVID-19) pandemic. Informed by the literature on SDGs and using the “inclusive development concept” by Gupta and Vegelin, literature search was done in Google Scholar, PubMed Central, as well as, searching of references in the relevant articles identified using search terms from the six SDGs that are directly related to One Health. In the context of the SDGs, in order to achieve One Health through inclusive governance, and tackle inequalities, the following needs to be considered and addressed: increasing number of armed conflicts; ongoing COVID-19 pandemic; ensuring availability of water and sanitation facilities; improving city and urban areas planning to cope with climate change; improving governance arrangements for addressing climate change factoring gender and human rights; multisectoral planning for conservation of oceans, seas, and marine resources; balancing trade regulation of wildlife trade with conservation efforts; need for a research collaborative involving experts from environmental sciences, wildlife, agriculture and human health to study and develop scientific evidence on contribution of changes in land use practices to occurrence of zoonotic diseases; and need of a legislation for promoting animal welfare to protect public health. Also, inclusion of people with disabilities in the use of digital technologies is critical.

Abstract Radiation damage in biological systems is initiated by free radicals and progresses with time through a variety of mechanisms. The time-scale and details of these mechanisms are briefly reviewed. Because of the variety of mechanisms of radio-biological damage, any single radio-protective or therapeutic agent can be only partially effective. The potential of and need for simultaneously using several radio-protective and therapeutic agents, including sulfhydryl compounds, superoxide dismutase, antioxidant proteins, and DNA repair enzymes, are examined, based on a priori considerations of the consequences of radiation exposure.

Background and Aims: Alcohol-associated liver disease (ALD) accounts for 70% of liver-related deaths in Europe, with no effective approved therapies. Although mitochondrial dysfunction is one of the earliest manifestations of alcohol-induced injury, restoring mitochondrial activity remains a problematic strategy due to oxidative stress. Here, we identify methylation-controlled J protein (MCJ) as a mediator for ALD progression and hypothesize that targeting MCJ may help in recovering mitochondrial fitness without collateral oxidative damage. Approach and Results: C57BL/6 mice [wild-type (Wt)] Mcj knockout and Mcj liver-specific silencing (MCJ-LSS) underwent the NIAAA dietary protocol (Lieber-DeCarli diet containing 5% (vol/vol) ethanol for 10 days, plus a single binge ethanol feeding at day 11). To evaluate the impact of a restored mitochondrial activity in ALD, the liver, gut, and pancreas were characterized, focusing on lipid metabolism, glucose homeostasis, intestinal permeability, and microbiota composition. MCJ, a protein acting as an endogenous negative regulator of mitochondrial respiration, is downregulated in the early stages of ALD and increases with the severity of the disease. Whole-body deficiency of MCJ is detrimental during ALD because it exacerbates the systemic effects of alcohol abuse through altered intestinal permeability, increased endotoxemia, and dysregulation of pancreatic function, which overall worsens liver injury. On the other hand, liver-specific Mcj silencing prevents main ALD hallmarks, that is, mitochondrial dysfunction, steatosis, inflammation, and oxidative stress, as it restores the NAD+/NADH ratio and SIRT1 function, hence preventing de novo lipogenesis and improving lipid oxidation. Conclusions: Improving mitochondrial respiration by liver-specific Mcj silencing might become a novel therapeutic approach for treating ALD.

The continual spread of novel coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), posing a severe threat to the health worldwide. The main protease (Mpro, alias 3CLpro) of SARS-CoV-2 is a crucial enzyme for the maturation of viral particles and is a very attractive target for designing drugs to treat COVID-19. Here, we propose a multiple conformation-based virtual screening strategy to discover inhibitors that can target SARS-CoV-2 Mpro. Based on this strategy, nine Mpro structures and a protein mimetics library with 8960 commercially available compounds were prepared to carry out ensemble docking for the first time. Five of the nine structures are apo forms presented in different conformations, whereas the other four structures are holo forms complexed with different ligands. The surface plasmon resonance assay revealed that 6 out of 49 compounds had the ability to bind to SARS-CoV-2 Mpro. The fluorescence resonance energy transfer experiment showed that the biochemical half-maximal inhibitory concentration (IC50) values of the six compounds could hamper Mpro activities ranged from 0.69 ± 0.05 to 2.05 ± 0.92 μM. Evaluation of antiviral activity using the cell-based assay indicated that two compounds (Z1244904919 and Z1759961356) could strongly inhibit the cytopathic effect and reduce replication of the living virus in Vero E6 cells with the half-maximal effective concentrations (EC50) of 4.98 ± 1.83 and 8.52 ± 0.92 μM, respectively. The mechanism of the action for the two inhibitors were further elucidated at the molecular level by molecular dynamics simulation and subsequent binding free energy analysis. As a result, the discovered noncovalent reversible inhibitors with novel scaffolds are promising antiviral drug candidates, which may be used to develop the treatment of COVID-19.

Activated sludge from municipal wastewater treatment processes can be used directly for the production of biodegradable polyesters from the family of polyhydroxyalkanoates (PHAs). However, municipal activated sludge typically cannot accumulate PHAs to very high levels and often low yields of polymer produced on substrate are observed. In the present work, it was found that the presence of calcium promotes selective growth and enrichment of the PHA-storing biomass fraction and significantly improved both PHA contents and yields. Calcium addition resulted in PHA contents of 0.60 ± 0.03 gPHA/gVSS and average PHA yields on substrate of 0.49 ± 0.03 gCODPHA/gCODHAc compared to 0.35 ± 0.01 gPHA/gVSS and 0.19 ± 0.01 gCODPHA/gCODHAc without calcium addition. After 48 h, three times more PHA was produced compared to control experiments without calcium addition. Higher PHA content and selective biomass production is proposed to be a consequence of calcium dependent increased levels of passive acetate uptake. Such more efficient substrate uptake could be related to a formation of calcium acetate complexes. Findings lead to bioprocess methods to stimulate a short-term selective growth of PHA-storing microorganisms and this enables improvements to the techno-economic feasibility for municipal waste activated sludge to become a generic resource for industrial scale PHA production.

AbstractDengue is hyperendemic in Brazil, with outbreaks affecting all regions. Previous studies identified geographical barriers to dengue transmission in Brazil, beyond which certain areas, such as South Brazil and the Amazon rainforest, were relatively protected from outbreaks. Recent data shows these barriers are being eroded. In this study, we explore the drivers of this expansion and identify the current limits to the dengue transmission zone. We used a spatio-temporal additive model to explore the associations between dengue outbreaks and temperature suitability, urbanisation, and connectivity to the Brazilian urban network. The model was applied to a binary outbreak indicator, assuming the official threshold value of 300 cases per 100,000 residents, for Brazil’s municipalities between 2001 and 2020. We found a nonlinear relationship between higher levels of connectivity to the Brazilian urban network and the odds of an outbreak, with lower odds in metropoles compared to regional capitals. The number of months per year with suitable temperature conditions for Aedes mosquitoes was positively associated with the dengue outbreak occurrence. Temperature suitability explained most interannual and spatial variation in South Brazil, confirming this geographical barrier is influenced by lower seasonal temperatures. Municipalities that had experienced an outbreak previously had double the odds of subsequent outbreaks, indicating that dengue tends to become established in areas after introduction. We identified geographical barriers to dengue transmission in South Brazil, western Amazon, and along the northern coast of Brazil. Although a southern barrier still exists, it has shifted south, and the Amazon no longer has a clear boundary. Few areas of Brazil remain protected from dengue outbreaks. Communities living on the edge of previous barriers are particularly susceptible to future outbreaks as they lack immunity. Control strategies should target regions at risk of future outbreaks as well as those currently within the dengue transmission zone.Author summaryDengue is a mosquito-borne disease that has expanded rapidly around the world due to increased urbanisation, global mobility and climate change. In Brazil, geographical barriers to dengue transmission exist, beyond which certain areas including South Brazil and the Amazon rainforest are relatively protected from outbreaks. However, we found that the previous barrier in South Brazil has shifted futher south as a result of increased temperature suitability. The previously identified barrier protecting the western Amazon no longer exists. This is particularly concerning as we found dengue outbreaks tend to become established in areas after introduction. Highly influential cities with many transport links had increased odds of an outbreak. However, the most influencial cities had lower odds of an outbreak than cities connected regionally. This study highlights the importance of monitoring the expansion of dengue outbreaks and designing disease prevention strategies for areas at risk of future outbreaks as well as areas in the established dengue transmission zone.

The application of neutron emitting radioisotopes in brachytherapy facilitates the use of the higher biological effectiveness of neutrons compared to photons in treating some cancers. Different types of high intensity sources are in use for the treatment of different cancers. To improve the therapy of bulky tumors the dose can be augmented by the additional use of the boron capture reaction of thermal neutrons. This requires information about the thermal neutron dose component around the Cf source. In this work, a Mg/Ar‐ionization chamber internally coated with was used to measure the thermal neutrons. These measurements were performed on two different sources, one in use in the Gershenson Radiation Oncology Center at Harper Hospital in Detroit, MI, and one at the University Hospital of Chiang Mai in Chiang Mai, Thailand. The results of these measurements are compared and indicate that the differences in the construction of the sources influence the thermal dose component.