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Background Tauopathies are a class of neurodegenerative disorders characterized by neuronal and/or glial tau-positive inclusions. Main body Clinically, tauopathies can present with a range of phenotypes that include cognitive/behavioral-disorders, movement disorders, language disorders and non-specific amnestic symptoms in advanced age. Pathologically, tauopathies can be classified based on the predominant tau isoforms that are present in the inclusion bodies (i.e., 3R, 4R or equal 3R:4R ratio). Imaging, cerebrospinal fluid (CSF) and blood-based tau biomarkers have the potential to be used as a routine diagnostic strategy and in the evaluation of patients with tauopathies. As tauopathies are strongly linked neuropathologically and genetically to tau protein abnormalities, there is a growing interest in pursuing of tau-directed therapeutics for the disorders. Here we synthesize emerging lessons on tauopathies from clinical, pathological, genetic, and experimental studies toward a unified concept of these disorders that may accelerate the therapeutics. Conclusions Since tauopathies are still untreatable diseases, efforts have been made to depict clinical and pathological characteristics, identify biomarkers, elucidate underlying pathogenesis to achieve early diagnosis and develop disease-modifying therapies.

The quantum repeater protocol is a promising approach for implementing long-distance quantum communication and large-scale quantum networks. A key idea of the quantum repeater protocol is to use long-lived quantum memories to achieve an efficient entanglement connection between different repeater segments, with polynomial scaling. Here, we report an experiment that realizes the efficient connection of two quantum repeater segments via on-demand entanglement swapping through the use of two atomic quantum memories with storage times of tens of milliseconds. With the memory enhancement, acceleration in the scaling is demonstrated in the rate for a successful entanglement connection. Experimental realization of the entanglement connection of two quantum repeater segments with an efficient memory-enhanced scaling demonstrates a key advantage of the quantum repeater protocol, creating a cornerstone for the development of future large-scale quantum networks.Two quantum repeater segments are connected via on-demand entanglement swapping by using two atomic quantum memories. The efficiency improves from a quadratic scaling to a linear one with the preparation efficiency of the atom–photon entanglement.

Non-variceal upper gastrointestinal bleeding remains an important emergency condition, leading to significant morbidity and mortality. As endoscopic therapy is the ’gold standard' of management, treatment of these patients can be considered in three stages: pre-endoscopic treatment, endoscopic haemostasis and post-endoscopic management. Since publication of the Asia-Pacific consensus on non-variceal upper gastrointestinal bleeding (NVUGIB) 7 years ago, there have been significant advancements in the clinical management of patients in all three stages. These include pre-endoscopy risk stratification scores, blood and platelet transfusion, use of proton pump inhibitors; during endoscopy new haemostasis techniques (haemostatic powder spray and over-the-scope clips); and post-endoscopy management by second-look endoscopy and medication strategies. Emerging techniques, including capsule endoscopy and Doppler endoscopic probe in assessing adequacy of endoscopic therapy, and the pre-emptive use of angiographic embolisation, are attracting new attention. An emerging problem is the increasing use of dual antiplatelet agents and direct oral anticoagulants in patients with cardiac and cerebrovascular diseases. Guidelines on the discontinuation and then resumption of these agents in patients presenting with NVUGIB are very much needed. The Asia-Pacific Working Group examined recent evidence and recommends practical management guidelines in this updated consensus statement.

Self-assembled hosts, inspired by biological receptors and catalysts, show application potential in sustainable synthesis, energy conversion and medicine. Implementing multiple functionalities in the form of distinguishable building blocks, however, is difficult without risking narcissistic self-sorting or a statistical mess. Here we report a systematic series of integratively self-assembled heteroleptic cages in which two square-planar Pd II cations are bridged by four different bis-pyridyl ligands, A, B, C and D, via synergistic effects to exclusively form a single isomer—the lantern-shaped cage [Pd 2 ABCD]. This self-sorting goal—forming just one out of 55 possible structures—is reached under full thermodynamic control and can be realized progressively (by combining progenitors, such as [Pd 2 A 2 C 2 ] with [Pd 2 B 2 D 2 ]), directly from ligands and Pd II cations or by mixing all four corresponding homoleptic cages. The rational design of complex multicomponent assemblies that enables the modular incorporation of diverse chemical moieties will advance their applicability in functional nanosystems. Metal-mediated self-assembly of organic building blocks is a powerful strategy to generate complex supramolecular objects. The non-statistical combination of multiple different components, however, has been a major challenge. Now integrative self-sorting of low-symmetry multicomponent cages has been achieved by combining shape complementarity and selective backbone interactions under thermodynamic control.

Ethylene oxide (EtO) is a highly reactive organic compound that is mainly used as a sterilizing agent. However, to date, the effects of EtO on the cardiovascular system are not clear. We aimed to explore the association between blood EtO levels and the risk of cardiovascular disease (CVD) in the general US population. We obtained information on blood levels of EtO and CVD outcomes in 3,410 participants from the National Health and Nutritional Examination Survey (NHANES) 2013–2014 and 2015–2016. Logistic regression models were applied to calculate the odds ratios (ORs) and 95% confidence intervals (95% CIs) for the association between EtO and risk of all CVD as well as subtypes of CVD. Linear regression analyses were used to estimate the associations of EtO with potential mechanistic parameters of CVD, including blood pressure, blood lipid levels and inflammatory parameters. Higher blood levels of EtO were associated with an increased risk of all CVD ( p for trend = 0.003), with an adjusted OR (95% CI) in the highest quartile of 1.94 (1.24, 3.02) compared with the lowest quartile as a reference. Higher concentrations of EtO were positively associated with the risk of angina ( p for trend = 0.04) and heart attack ( p for trend = 0.011). In addition, the concentration of EtO was positively associated with the levels of triglycerides, white blood cells, lymphocytes, monocytes, neutrophils and eosinophils ( p = 0.003 for eosinophils and p < 0.001 for the others) and negatively associated with the level of high-density lipoprotein cholesterol ( p < 0.001). We found that exposure to EtO was associated with angina, heart attack and all CVD in a large representative US population. Furthermore, EtO may induce CVD through the inflammatory response and abnormal fatty acid metabolism.

Quantification and attribution of long-term tropospheric ozone trends are critical for understanding the impact of human activity and climate change on atmospheric chemistry but are also challenged by the limited coverage of long-term ozone observations in the free troposphere where ozone has higher production efficiency and radiative potential compared to that at the surface. In this study, we examine observed tropospheric ozone trends, their attributions, and radiative impacts from 1995–2017 using aircraft observations from the In-service Aircraft for a Global Observing System database (IAGOS), ozonesondes, and a multi-decadal GEOS-Chem chemical model simulation. IAGOS observations above 11 regions in the Northern Hemisphere and 19 of 27 global ozonesonde sites have measured increases in tropospheric ozone (950–250 hPa) by 2.7 ± 1.7 and 1.9 ± 1.7 ppbv per decade on average, respectively, with particularly large increases in the lower troposphere (950–800 hPa) above East Asia, the Persian Gulf, India, northern South America, the Gulf of Guinea, and Malaysia/Indonesia by 2.8 to 10.6 ppbv per decade. The GEOS-Chem simulation driven by reanalysis meteorological fields and the most up-to-date year-specific anthropogenic emission inventory reproduces the overall pattern of observed tropospheric ozone trends, including the large ozone increases over the tropics of 2.1–2.9 ppbv per decade and above East Asia of 0.5–1.8 ppbv per decade and the weak tropospheric ozone trends above North America, Europe, and high latitudes in both hemispheres, but trends are underestimated compared to observations. GEOS-Chem estimates an increasing trend of 0.4 Tg yr−1 of the tropospheric ozone burden in 1995–2017. We suggest that uncertainties in the anthropogenic emission inventory in the early years of the simulation (e.g., 1995–1999) over developing regions may contribute to GEOS-Chem's underestimation of tropospheric ozone trends. GEOS-Chem sensitivity simulations show that changes in global anthropogenic emission patterns, including the equatorward redistribution of surface emissions and the rapid increases in aircraft emissions, are the dominant factors contributing to tropospheric ozone trends by 0.5 Tg yr−1. In particular, we highlight the disproportionately large, but previously underappreciated, contribution of aircraft emissions to tropospheric ozone trends by 0.3 Tg yr−1, mainly due to aircraft emitting NOx in the mid-troposphere and upper troposphere where ozone production efficiency is high. Decreases in lower-stratospheric ozone and the stratosphere–troposphere flux in 1995–2017 contribute to an ozone decrease at mid-latitudes and high latitudes. We estimate the change in tropospheric ozone radiative impacts from 1995–1999 to 2013–2017 is +18.5 mW m−2, with 43.5 mW m−2 contributed by anthropogenic emission changes (20.5 mW m−2 alone by aircraft emissions), highlighting that the equatorward redistribution of emissions to areas with strong convection and the increase in aircraft emissions are effective for increasing tropospheric ozone's greenhouse effect.

ObjectiveThe gut microbiota-derived metabolite, trimethylamine N-oxide (TMAO) plays an important role in cardiovascular disease (CVD). The fasting plasma TMAO was shown as a prognostic indicator of CVD incident in patients and raised the interest of intervention targeting gut microbiota. Here we develop a clinically applicable method called oral carnitine challenge test (OCCT) for TMAO-related therapeutic drug efforts assessment and personalising dietary guidance.DesignA pharmacokinetic study was performed to verify the design of OCCT protocol. The OCCT was conducted in 23 vegetarians and 34 omnivores to validate gut microbiota TMAO production capacity. The OCCT survey was integrated with gut microbiome, host genotypes, dietary records and serum biochemistry. A humanised gnotobiotic mice study was performed for translational validation.ResultsThe OCCT showed better efficacy than fasting plasma TMAO to identify TMAO producer phenotype. The omnivores exhibited a 10-fold higher OR to be high TMAO producer than vegetarians. The TMAO-associated taxa found by OCCT in this study were consistent with previous animal studies. The TMAO producer phenotypes were also reproduced in humanised gnotobiotic mice model. Besides, we found the faecal CntA gene was not associated with TMAO production; therefore, other key relevant microbial genes might be involved. Finally, we demonstrated the urine TMAO exhibited a strong positive correlation with plasma TMAO (r=0.92, p<0.0001) and improved the feasibility of OCCT.ConclusionThe OCCT can be used to identify TMAO-producer phenotype of gut microbiota and may serve as a personal guidance in CVD prevention and treatment.Trial registration number NCT02838732; Results.

Background Water stress is one of the serious abiotic stresses that negatively influences the growth, development and production of sugarcane in arid and semi-arid regions. However, silicon (Si) has been applied as an alleviation strategy subjected to environmental stresses. Methods In this experiment, Si was applied as soil irrigation in sugarcane plants to understand the mitigation effect of Si against harmful impact of water stress on photosynthetic leaf gas exchange. Results In the present study we primarily revealed the consequences of low soil moisture content, which affect overall plant performance of sugarcane significantly. Silicon application reduced the adverse effects of water stress by improving the net photosynthetic assimilation rate ( A net ) 1.35–18.75%, stomatal conductance to water vapour (gs) 3.26–21.57% and rate of transpiration (E) 1.16–17.83%. The mathematical models developed from the proposed hypothesis explained the functional relationships between photosynthetic responses of Si application and water stress mitigation. Conclusions Silicon application showed high ameliorative effects on photosynthetic responses of sugarcane to water stress and could be used for mitigating environmental stresses in other crops, too, in future.