Integrated analyses of single-cell atlases reveal age, gender, and smoking status associations with cell type-specific expression of mediators of SARS-CoV-2 viral entry and highlights inflammatory programs in putative target cells

The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, creates an urgent need for identifying molecular mechanisms that mediate viral entry, propagation, and tissue pathology. Cell membrane bound angiotensin-converting enzyme 2 (ACE2) and associated proteases, transmembrane protease serine 2 (TMPRSS2) and Cathepsin L (CTSL), were previously identified as mediators of SARS-CoV2 cellular entry. Here, we assess the cell type-specific RNA expression of ACE2, TMPRSS2, and CTSL through an integrated analysis of 107 single-cell and single-nucleus RNA-Seq studies, including 22 lung and airways datasets (16 unpublished), and 85 datasets from other diverse organs. Joint expression of ACE2 and the accessory proteases identifies specific subsets of respiratory epithelial cells as putative targets of viral infection in the nasal passages, airways, and alveoli. Cells that co-express ACE2 and proteases are also identified in cells from other organs, some of which have been associated with COVID-19 transmission or pathology, including gut enterocytes, corneal epithelial cells, cardiomyocytes, heart pericytes, olfactory sustentacular cells, and renal epithelial cells. Performing the first meta-analyses of scRNA-seq studies, we analyzed 1,176,683 cells from 282 nasal, airway, and lung parenchyma samples from 164 donors spanning fetal, childhood, adult, and elderly age groups, associate increased levels of ACE2, TMPRSS2, and CTSL in specific cell types with increasing age, male gender, and smoking, all of which are epidemiologically linked to COVID-19 susceptibility and outcomes. Notably, there was a particularly low expression of ACE2 in the few young pediatric samples in the analysis. Further analysis reveals a gene expression program shared by ACE2(+)TMPRSS2(+) cells in nasal, lung and gut tissues, including genes that may mediate viral entry, subtend key immune functions, and mediate epithelial-macrophage cross-talk. Amongst these are IL6, its receptor and co-receptor, IL1R, TNF response pathways, and complement genes. Cell type specificity in the lung and airways and smoking effects were conserved in mice. Our analyses suggest that differences in the cell type-specific expression of mediators of SARS-CoV-2 viral entry may be responsible for aspects of COVID-19 epidemiology and clinical course, and point to putative molecular pathways involved in disease susceptibility and pathogenesis

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: A systematic analysis for the Global Burden of Disease Study 2015

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods: We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings: Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation: Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding: Bill & Melinda Gates Foundation

Modelling the simultaneous heat and mass transfer of direct contact membrane distillation in hollow fibre modules

This paper presents a new procedure for modelling the simultaneous heat and mass transfer in direct contact membrane distillation (DCMD) in a hollow fibre configuration. Iterative calculations in classic dimensionless analysis were applied to develop semi-empirical models, employing the analogy between heat and mass transfer. The procedure incorporated the significant effect of the membrane module's geometry: length and tortuosity of fibres in the bundle and fibres' size. Additionally, the new procedure showed the influence of the exponent β of Prandtl and Schmidt numbers on the validity of the models to simultaneously describe heat and mass transfer in the DCMD process. Current results agreed well with other analyses in the literature. The value close to 0.33 of β, as conventionally used, could be applied for heat transfer and minimal mass transfer. In other more intensive mass transfer cases, it was found that the values of β could go up to 0.55. The new models demonstrated a linear relationship between heat and mass fluxes and their respective driving forces, namely conductive heat flux against temperature gradient and mass flux against water vapour pressure difference across the membrane. Finally these semi-empirical models were applied to evaluate the performance of various hollow fibre modules of different length and types

Simulation and optimisation of direct contact membrane distillation for energy efficiency

This paper describes the formulation of a computational framework for simulating and optimising DCMD to minimise the consumed energy. A simulation procedure for DCMD was established on the basis of equating heat and mass fluxes through different domains in the process. Steady-state simulations for a wide range of operating conditions were carried out. It was revealed that the highest achievable energy efficiency of DCMD within the tested range was about 49.9%. A double loop optimisation problem was formulated in MATLAB to solve the highly nonlinear equations with unknown outlet and membrane surface conditions to implement the simulation procedure. An additional outer loop was also implemented to accommodate the dynamic condition of a real lab-scale DCMD system concentrating 1.5 kg glucose solution from 30 to 60% w/w. A pseudo-real-time dynamic optimisation was performed to minimise the energy expenses for the DCMD process. This energy accounted for the heat exchanged between the feed and permeate streams within the membrane module and the power for their pumping, while maintaining a minimum mass flux of 0.5 kg m- 2 h- 1. The optimal operating conditions found in this study could save the total energy consumption by 26.3%

Results on attempts in management of HLB under small scale in Vietnam and initiation in screening for HLB tolerant from varieties/clones belonging to Rutaceae

In the Mekong Delta, Vietnam, Citrus Huanglongbing (HLB) was officially announced in 1994 and its causal organism was described by Bove and Garnier in 1995 to be Candidatus Liberibacter asiaticus. Throughout the years, intensive works have been carried out for HLB control under small scale orchards and the achievements are discussed, the model for effective control of HLB under small scale which could elongate the life cycle of citrus tree for better and longer harvesting. In addition, there were 130 rutaceae related accessions had been collected and screened for HLB tolerance; the results revealed that the serverity of HLB infection was less on Hanh/Tac/Quat (Citrus microcarpa) and Long Co co pummelo (Citrus maxima) than that on orange and mandarin. The wild Rutaceae species/clones such as Quyt Dang, Quyt rung, Cam rung, Buoi Rung, Buoi Dang, Buoi Bung, Mac Run, Mac Mat, Can Thang, Quach, Nguyet Que, Kim quit, Truc, Com Ruou, Dau dau ba la, Ca ri, Da tu bien and Gioi Lom were symptomless under transmission conditions and had a negative reaction by PCR tests. In a molecular study, 38 primers have been designed and used for screening of HLB tolerance capacity of 49 varieties/clones belonging to Rutaceae. The preliminary results shown that the tolerant varieties was grouped into Group D, which somehow matched with the tolerant group screened under screenhouse conditions

Results on attempts in management of HLB under small scale in Vietnam and initiation in screening for HLB tolerant from varieties/clones belonging to Rutaceae

In the Mekong Delta, Vietnam, Citrus Huanglongbing (HLB) was officially announced in 1994 and its causal organism was described by Bove and Garnier in 1995 to be Candidatus Liberibacter asiaticus. Throughout the years, intensive works have been carried out for HLB control under small scale orchards and the achievements are discussed, the model for effective control of HLB under small scale which could elongate the life cycle of citrus tree for better and longer harvesting. In addition, there were 130 rutaceae related accessions had been collected and screened for HLB tolerance; the results revealed that the serverity of HLB infection was less on Hanh/Tac/Quat (Citrus microcarpa) and Long Co co pummelo (Citrus maxima) than that on orange and mandarin. The wild Rutaceae species/clones such as Quyt Dang, Quyt rung, Cam rung, Buoi Rung, Buoi Dang, Buoi Bung, Mac Run, Mac Mat, Can Thang, Quach, Nguyet Que, Kim quit, Truc, Com Ruou, Dau dau ba la, Ca ri, Da tu bien and Gioi Lom were symptomless under transmission conditions and had a negative reaction by PCR tests. In a molecular study, 38 primers have been designed and used for screening of HLB tolerance capacity of 49 varieties/clones belonging to Rutaceae. The preliminary results shown that the tolerant varieties was grouped into Group D, which somehow matched with the tolerant group screened under screenhouse conditions

High resolution simulation of recent Arctic and Antarctic stratospheric chemical ozone loss compared to observations

Simulations of polar ozone losses were performed using the three-dimensional high-resolution (1° × 1°) chemical transport model MIMOSA-CHIM. Three Arctic winters 1999–2000, 2001–2002, 2002–2003 and three Antarctic winters 2001, 2002, and 2003 were considered for the study. The cumulative ozone loss in the Arctic winter 2002–2003 reached around 35% at 475K inside the vortex, as compared to more than 60% in 1999–2000. During 1999–2000, denitrification induces a maximum of about 23% extra ozone loss at 475K as compared to 17% in 2002–2003. Unlike these two colder Arctic winters, the 2001–2002 Arctic was warmer and did not experience much ozone loss. Sensitivity tests showed that the chosen resolution of 1° ×1° provides a better evaluation of ozone loss at the edge of the polar vortex in high solar zenith angle conditions. The simulation results for ozone, ClO, HNO3, N2O, and NOy for winters 1999–2000 and 2002–2003 were compared with measurements on board ER-2 and Geophysica aircraft respectively. Sensitivity tests showed that increasing heating rates calculated by the model by 50% and doubling the PSC (Polar Stratospheric Clouds) particle density (from 5 × 10-3 to 10-2 cm-3) refines the agreement with in situ ozone, N2O and NOy levels. In this configuration, simulated ClO levels are increased and are in better agreement with observations in January but are overestimated by about 20% in March. The use of the Burkholder et al. (1990) Cl2O2 absorption cross-sections slightly increases further ClO levels especially in high solar zenith angle conditions. Comparisons of the modelled ozone values with ozonesonde measurement in the Antarctic winter 2003 and with Polar Ozone and Aerosol Measurement III (POAM III) measurements in the Antarctic winters 2001 and 2002, shows that the simulations underestimate the ozone loss rate at the end of the ozone destruction period. A slightly better agreement is obtained with the use of Burkholder et al. (1990) Cl2O2 absorption cross-sections