Characterising global antimicrobial resistance research explains why One Health solutions are slow in development: An application of AI-based gap analysis.

The global health crisis posed by increasing antimicrobial resistance (AMR) implicitly requires solutions based a One Health approach, yet multisectoral, multidisciplinary research on AMR is rare and huge knowledge gaps exist to guide integrated action. This is partly because a comprehensive survey of past research activity has never performed due to the massive scale and diversity of published information. Here we compiled 254,738 articles on AMR using Artificial Intelligence (AI; i.e., Natural Language Processing, NLP) methods to create a database and information retrieval system for knowledge extraction on research perfomed over the last 20 years. Global maps were created that describe regional, methodological, and sectoral AMR research activities that confirm limited intersectoral research has been performed, which is key to guiding science-informed policy solutions to AMR, especially in low-income countries (LICs). Further, we show greater harmonisation in research methods across sectors and regions is urgently needed. For example, differences in analytical methods used among sectors in AMR research, such as employing culture-based versus genomic methods, results in poor communication between sectors and partially explains why One Health-based solutions are not ensuing. Therefore, our analysis suggest that performing culture-based and genomic AMR analysis in tandem in all sectors is crucial for data integration and holistic One Health solutions. Finally, increased investment in capacity development in LICs should be prioritised as they are places where the AMR burden is often greatest. Our open-access database and AI methodology can be used to further develop, disseminate, and create new tools and practices for AMR knowledge and information sharing.

Sanguinarine modulates microglial function via PPARγ activation and protects against CNS demyelination.

Microglia aggregate in regions of active inflammation and demyelination in the CNS of multiple sclerosis (MS) patients and are considered pivotal in the disease process. Targeting microglia is a promising therapeutic approach for myelin repair. Previously, we identified two candidates for microglial modulation and remyelination using a Connectivity Map (CMAP)-based screening strategy. Interestingly, with results that overlapped, sanguinarine (SAN) emerged as a potential drug candidate to modulate microglial polarization and promote remyelination. In the current study, we demonstrate the efficacy of SAN in mitigating the MS-like experimental autoimmune encephalomyelitis (EAE) in a dose-dependent manner. Meanwhile, prophylactic administration of a medium dose (2.5 mg/kg) significantly reduces disease incidence and ameliorates clinical signs in EAE mice. At the cellular level, SAN reduces the accumulation of microglia in the spinal cord. Morphological analyses and immunophenotyping reveal a less activated state of microglia following SAN administration, supported by decreased inflammatory cytokine production in the spinal cord. Mechanistically, SAN skews primary microglia towards an immunoregulatory state and mitigates proinflammatory response through PPARγ activation. This creates a favorable milieu for the differentiation of oligodendrocyte progenitor cells (OPCs) when OPCs are incubated with conditioned medium from SAN-treated microglia. We further extend our investigation into the cuprizone-induced demyelinating model, confirming that SAN treatment upregulates oligodendrocyte lineage genes and increases myelin content, further suggesting its pro-myelination effect. In conclusion, our data propose SAN as a promising candidate adding to the preclinical therapeutic arsenal for regulating microglial function and promoting myelin repair in CNS demyelinating diseases such as MS.

Harnessing biological nitrogen fixation in plant leaves.

The importance of biological nitrogen fixation (BNF) in securing food production for the growing world population with minimal environmental cost has been increasingly acknowledged. Leaf surfaces are one of the biggest microbial habitats on Earth, harboring diverse free-living N2-fixers. These microbes inhabit the epiphytic and endophytic phyllosphere and contribute significantly to plant N supply and growth. Here, we summarize the contribution of phyllosphere-BNF to global N cycling, evaluate the diversity of leaf-associated N2-fixers across plant hosts and ecosystems, illustrate the ecological adaptation of N2-fixers to the phyllosphere, and identify the environmental factors driving BNF. Finally, we discuss potential BNF engineering strategies to improve the nitrogen uptake in plant leaves and thus sustainable food production.

Observations and modeling of OH and HO2 radicals in Chengdu, China in summer 2019.

This study reports on the first continuous measurements of ambient OH and HO2 radicals at a suburban site in Chengdu, Southwest China, which were collected during 2019 as part of a comprehensive field campaign 'CompreHensive field experiment to explOre the photochemical Ozone formation mechaniSm in summEr - 2019 (CHOOSE-2019)'. The mean concentrations (11:00-15:00) of the observed OH and HO2 radicals were 9.5 × 106 and 9.0 × 108 cm-3, respectively. To investigate the state-of-the-art chemical mechanism of radical, closure experiments were conducted with a box model, in which the RACM2 mechanism updated with the latest isoprene chemistry (RACM2-LIM1) was used. In the base run, OH radicals were underestimated by the model for the low-NO regime, which was likely due to the missing OH recycling. However, good agreement between the observed and modeled OH concentrations was achieved when an additional species X (equivalent to 0.25 ppb of NO mixing ratio) from one new OH regeneration cycle (RO2 + X â†’ HO2, HO2 + X â†’ OH) was added into the model. Additionally, in the base run, the model could reproduce the observed HO2 concentrations. Discrepancies in the observed and modeled HO2 concentrations were found in the sensitivity runs with HO2 heterogeneous uptake, indicating that the impact of the uptake may be less significant in Chengdu because of the relatively low aerosol concentrations. The ROx (= OH + HO2 + RO2) primary source was dominated by photolysis reactions, in which HONO, O3, and HCHO photolysis accounted for 34%, 19%, and 23% during the daytime, respectively. The efficiency of radical cycling was quantified by the radical chain length, which was determined by the NO to NO2 ratio successfully. The parameterization of the radical chain length may be very useful for the further determinations of radical recycling.

Dynamic simulation of the optimal allocation of water resources via the introduction of integrated water environmental policies in Baoding, China.

With rapid industrialization and urbanization, regional water shortages and water quality deterioration have posed great challenges for the sustainable development of cities in North China, especially those with a large demand for agricultural irrigation water. Based on an input-output analysis, this paper develops a dynamic optimization model consisting of three sub-models and multiple constraint conditions to solve the water crisis of Baoding, a typical city experiencing water shortages and serious water pollution in North China. The water resource carrying capacity (WRCC) indicator is introduced in the analysis of the results to comprehensively assess the effect of integrated water environmental policies (IWEPs) from 2013 to 2025. In the optimal scenario, the annual chemical oxygen demand (COD) discharge and annual water demand in Baoding can be reduced by 2.6% and 0.6%, respectively, with an annual gross regional product (GRP) growth rate of 7.52%. The WRCC can be improved from moderately overloaded to weakly unsaturated, which indicates that water resources can meet the socioeconomic development requirements. The results demonstrate the effectiveness of the linear optimization model with input-output analysis in coordinating the relationships among water demand, water environment protection, and economic development, and the IWEPs provide an applicable reference for decision-makers in Baoding and other similar cities in North China to address deteriorating water systems.

Winter photochemistry in Beijing: Observation and model simulation of OH and HO2 radicals at an urban site.

A field campaign was conducted from November to December 2017 at the campus of Peking University (PKU) to investigate the formation mechanism of the winter air pollution in Beijing with the measurement of hydroxyl and hydroperoxyl radical (OH and HO2) with the support from comprehensive observation of trace gases compounds. The extent of air pollution depends on meteorological conditions. The daily maximum OH radical concentrations are on average 2.0 × 106 cm-3 and 1.5 × 106 cm-3 during the clean and polluted episodes, respectively. The daily maximum HO2 radical concentrations are on average 0.4 × 108 cm-3 and 0.3 × 108 cm-3 during the clean and polluted episodes, respectively (diurnal averaged for one hour bin). A box model based on RACM2-LIM1 mechanism can reproduce the OH concentrations but underestimate the HO2 concentrations by 50% during the clean episode. The OH and HO2 concentrations are underestimated by 50% and 12 folds during the polluted episode, respectively. Strong dependence on nitric oxide (NO) concentration is found for both observed and modeled HO2 concentrations, with the modeled HO2 decreasing more rapidly than observed HO2, leading to severe HO2 underestimation at higher NO concentrations. The OH reactivity is calculated from measured and modeled species and inorganic compounds (carbon monoxide (CO), NO, and nitrogen dioxide (NO2)) make up 69%-76% of the calculated OH reactivity. The photochemical oxidation rate denoted by the OH loss rate increases by 3 times from the clean to polluted episodes, indicating the strong oxidation capacity in polluted conditions. The comparison between measurements at PKU site and a suburban site from one previous study shows that chemical conditions are similar in both urban and suburban areas. Hence, the strong oxidation capacity and its potential contribution to the pollution bursts are relatively homogeneous over the whole Beijing city and its surrounding areas.

Experiment and theoretical explanation of optical bistability in a single erbium-doped fiber ring laser.

Optical bistability phenomenon in a single fiber ring laser employing erbium-doped fiber (EDF) as gain medium is observed in our experiment. In the EDF amplifiers, the photons of pump light cannot completely transfer into that of signal light because of various attenuation factors. This part of loss (useless pump loss) and active spontaneous emission (ASE) can both lower the small-signal gain of the EDF, and can eventually result in the bistability phenomenon. The range of this bistability has a complicated relationship with the length of the EDF, the erbium-ion doping concentration, the cavity loss and the useless loss coefficient of the pump light.