Construction of the ETECFinder database for the characterization of enterotoxigenic Escherichia coli (ETEC) and revision of the VirulenceFinder web tool at the CGE website.

The identification of pathogens is essential for effective surveillance and outbreak detection, which lately has been facilitated by the decreasing cost of whole-genome sequencing (WGS). However, extracting relevant virulence genes from WGS data remains a challenge. In this study, we developed a web-based tool to predict virulence-associated genes in enterotoxigenic Escherichia coli (ETEC), which is a major concern for human and animal health. The database includes genes encoding the heat-labile toxin (LT) (eltA and eltB), heat-stable toxin (ST) (est), colonization factors CS1 through 30, F4, F5, F6, F17, F18, and F41, as well as toxigenic invasion and adherence loci (tia, tibAC, etpBAC, eatA, yghJ, and tleA). To construct the database, we revised the existing ETEC nomenclature and used the VirulenceFinder webtool at the CGE website [VirulenceFinder 2.0 (dtu.dk)]. The database was tested on 1,083 preassembled ETEC genomes, two BioProjects (PRJNA421191 with 305 and PRJNA416134 with 134 sequences), and the ETEC reference genome H10407. In total, 455 new virulence gene alleles were added, 50 alleles were replaced or renamed, and two were removed. Overall, our tool has the potential to greatly facilitate ETEC identification and improve the accuracy of WGS analysis. It can also help identify potential new virulence genes in ETEC. The revised nomenclature and expanded gene repertoire provide a better understanding of the genetic diversity of ETEC. Additionally, the user-friendly interface makes it accessible to users with limited bioinformatics experience. IMPORTANCE: Detecting colonization factors in enterotoxigenic Escherichia coli (ETEC) is challenging due to their large number, heterogeneity, and lack of standardized tests. Therefore, it is important to include these ETEC-related genes in a more comprehensive VirulenceFinder database in order to obtain a more complete coverage of the virulence gene repertoire of pathogenic types of E. coli. ETEC vaccines are of great importance due to the severity of the infections, primarily in children. A tool such as this could assist in the surveillance of ETEC in order to determine the prevalence of relevant types in different parts of the world, allowing vaccine developers to target the most prevalent types and, thus, a more effective vaccine.

Interconnected and resilient: A CGE analysis of AI-driven cyberattacks in global trade.

The burgeoning interconnectedness of global trade in the digital age not only presents enticing opportunities but also harbors potent vulnerabilities of artificial intelligence (AI)-driven cyberattacks. This study explores the cascading impacts of these disruptive threats on economies, supply chains, and trade, utilizing the intricate lens of Computable General Equilibrium modeling. Through meticulously designed simulation scenarios, we illuminate the potential economic ramifications of cyberattacks, with a focus on regions heavily reliant on digital technologies and interwoven supply chains. The analysis reveals significant declines in real GDP, trade prices and volumes, and trade route disruptions across regions. Notably, economies like China, the United States, the United Kingdom, and the EU, due to their deep integration in global networks, face pronounced vulnerabilities. However, amidst this bleak landscape, hope emerges in the form of cyber resilience. The study showcases the effectiveness of proactive measures like adaptable production systems, diversified trade partners, and robust cybersecurity infrastructure in mitigating the adverse impacts of cyberattacks. Incorporating cyber resilience significantly dampens the reported negative consequences, highlighting the critical role of preparedness in combating digital warfare. This study underscores the urgent need for a global paradigm shift toward cyber resilience. Collective efforts to bolster cybersecurity infrastructures, foster international cooperation in threat intelligence, and establish open and resilient trade frameworks are crucial in navigating the treacherous labyrinth of AI-driven cyberattacks. By embracing resilience strategies and fostering global collaboration, we can pave the way for a more secure and prosperous digital future, where interconnectedness becomes a tool for progress, not a vulnerability to be exploited.

Assessing regional employment effects of the national emission trading scheme in China: Does Okun's law work?

Employment creation and climate change mitigation are core tasks for achieving sustainable development goals. Whether or not carbon mitigation policy facilitate employment deserves deep exploration. Through the construction of multi-regional dynamic computable general equilibrium model (CGE) with more scientific energy & environment block, this paper first evaluates regional employment effects of the national emission trading scheme (ETS) in China. Furthermore, we explore the Okun's law of the national ETS based on the mediating effect model. The results show that whether in carbon-intensive industries (CIIs) or non-carbon-intensive industries (NCIIs), employment effects of the national ETS are differentiated across regions. Specifically, the national ETS generally promotes CIIs' employment in Southern, Eastern, Middle Yangtze River and Southwest regions, and has negative effects on CIIs' employment in other regions. Meanwhile, the national ETS brings employment creation to NCIIs of Southern region, while there are opposite results in NCIIs of Northeast region and mixed results in NCIIs of other regions. Moreover, the Okun's law of the national ETS holds in CIIs of each region, but it not fits the data for NCIIs. Therefore, it is important for the Chinese government to consider the differentiated employment effects in different regions carefully rather than adopt one-size-fit-all solution when constructing the national carbon market.

Call for multi-policy approach: Synergistic effects of emissions trading scheme and energy efficiency policies.

Limited research exists on the synergistic effects of carbon emissions trading and energy efficiency policies despite their significance in achieving global carbon neutrality objectives. This study examines the synergistic effects of carbon emissions trading and energy efficiency policies on aspects of the environment, energy, and economy. Results show that the synergistic effect leads to an additional reduction of 1.2% in carbon emissions, along with a decrease of 4.2% in economic losses. Despite challenges like increased energy external dependency and carbon leakage, the synergistic effect shows a positive externality between policies, reducing the carbon intensity and marginal emission mitigation costs. Furthermore, these synergistic effects yield positive consequences for social welfare, particularly benefiting rural households and fostering equitable distribution of carbon mitigation benefits across societal groups. These findings underscore the importance of considering policy synergies between carbon emissions trading and energy efficiency policies to ensure the total effect of climate change mitigation strategies.

Contribution of the carbon tax, phase-out of thermoelectric power plants, and renewable energy subsidies for the decarbonization of Chile - A CGE model and microsimulations approach.

There are various climate policies to decarbonize the energy matrix of a country. In the case of Chile, a carbon tax of 5 USD/tCO2 was initially implemented, and later, a schedule was established for the phase-out of coal-fired thermoelectric plants, all the above in the absence of subsidies for non-conventional renewable energy (NCRE). This study uses a computable general equilibrium (CGE) model and microsimulations to assess the contribution of current climate policies and other more demanding scenarios that accelerate the decarbonization of the Chilean energy matrix, considering economic, environmental, and distributional impacts. Specifically, carbon taxes are simulated with and without complementary climate policies (phase-out of coal-fired power plants and NCRE subsidies). The results show that the scenarios that combine the three climate policies generate a greater decrease in greenhouse gas emissions (40.4% âˆ¼ 57.5%). Besides, the drop in GDP is more pronounced when coal-fired thermoelectric plants phase out (0.3% additional), and NCRE subsidies contribute to moderately reducing emissions. However, NCRE subsidies reduce the negative effect on households' expenditure and income, especially in the poorest quintile. Finally, microsimulations show marginal changes in income distribution and an increase of up to 0.4 percentage points in the poverty rate.

A recursive dynamic CGE approach to investigate environmental Kuznets curve.

The inverted U-shaped relationship between economic growth and environmental degradation is known as environmental Kuznets curve (EKC) and has been tested in many empirical studies since more than 3 decades. Technological change is one of the tools that can be used to examine the existence of EKC in CGE models. The objective is to extract EKC for G7 countries using a multi-regional CGE model and investigate the effects of some key factors affecting EKC using historical data for the period of 1861-2021. First, we have considered the effects of energy efficiency, on CO2 emissions, on carbon intensity and on economic growth. Then, EKC was extracted based on the obtained results. In addition, the effects of factors such as carbon tax, revenue recycling schemes and various types of substitution elasticities are evaluated on EKC. Our results show that, with a 3% improvement in productivity, by 2050, GDP will increase by nearly 12% and carbon emissions will decrease by 4.4%. The combination of such two effects has led to an inverted U-shaped relationship between economic growth and carbon emissions. Among the elasticity of substitutions, the elasticity of substitution of capital and energy, as well as the substitution elasticity of energy inputs has the greatest effect on EKC. The slope of EKC becomes negative if a carbon tax is imposed. The EKC moves downwards if carbon tax income is transferred to the production tax-cut in renewable sectors. The results suggest that carbon tax and its allocation to renewable sectors will improve environmental effects.

Electrophoretic characterization of LNP/AAV-encapsulated nucleic acids: Strengths and weaknesses.

The use of nucleic acids (NAs) has revolutionized medical approaches and ushered in a new era of combating various diseases. Accordingly, there is an increasing demand for accurate identification, localization, quantification, and characterization of NAs encapsulated in nonviral or viral vectors. The vast spectrum of molecular dimensions and intra- and intermolecular interactions presents a formidable obstacle for NA analytical development. Typically, the comprehensive analysis of encapsulated NAs, free NAs, and their spatial distribution poses a challenge that is seldom tackled in its complete complexity. The identification of appropriate physicochemical methodologies for large nonencapsulated or encapsulated NAs is particularly intricate and necessitates an evaluation of the analytical outcomes and their appropriateness in addressing critical quality attributes. In this work, we examine the analytics of non-encapsulated or encapsulated large NAs (>500 nucleotides) utilizing capillary electrophoresis (CE) and liquid chromatography (LC) methodologies such as free zone CE, gel CE, affinity CE, and ion pair high-performance liquid chromatography (HPLC). These methodologies create a complete picture of the NA's critical quality attributes, including quantity, identity, purity, and content ratio.

Malaria control and elimination in Kenya: economy-wide benefits and regional disparities.

BACKGROUND: Malaria remains a public health problem in Kenya despite several concerted control efforts. Empirical evidence regarding malaria effects in Kenya suggests that the disease imposes substantial economic costs, jeopardizing the achievement of sustainable development goals. The Kenya Malaria Strategy (2019-2023), which is currently being implemented, is one of several sequential malaria control and elimination strategies. The strategy targets reducing malaria incidences and deaths by 75% of the 2016 levels by 2023 through spending around Kenyan Shillings 61.9 billion over 5 years. This paper assesses the economy-wide implications of implementing this strategy. METHODS: An economy-wide simulation model is calibrated to a comprehensive 2019 database for Kenya, considering different epidemiological zones. Two scenarios are simulated with the model. The first scenario (GOVT) simulates the annual costs of implementing the Kenya Malaria Strategy by increasing government expenditure on malaria control and elimination programmes. The second scenario (LABOR) reduces malaria incidences by 75% in all epidemiological malaria zones without accounting for the changes in government expenditure, which translates into rising the household labour endowment (benefits of the strategy). RESULTS: Implementing the Kenya Malaria Strategy (2019-2023) enhances gross domestic product at the end of the strategy implementation period due to more available labour. In the short term, government health expenditure (direct malaria costs) increases significantly, which is critical in controlling and eliminating malaria. Expanding the health sector raises the demand for production factors, such as labour and capital. The prices for these factors rise, boosting producer and consumer prices of non-health-related products. Consequently, household welfare decreases during the strategy implementation period. In the long run, household labour endowment increases due to reduced malaria incidences and deaths (indirect malaria costs). However, the size of the effects varies across malaria epidemiological and agroecological zones depending on malaria prevalence and factor ownership. CONCLUSIONS: This paper provides policymakers with an ex-ante assessment of the implications of malaria control and elimination on household welfare across various malaria epidemiological zones. These insights assist in developing and implementing related policy measures that reduce the undesirable effects in the short run. Besides, the paper supports an economically beneficial long-term malaria control and elimination effect.

Genetic knockout of porcine GGTA1 or CMAH/GGTA1 is associated with the emergence of neo-glycans.

BACKGROUND: Pig-derived tissues could overcome the shortage of human donor organs in transplantation. However, the glycans with terminal α-Gal and Neu5Gc, which are synthesized by enzymes, encoded by the genes GGTA1 and CMAH, are known to play a major role in immunogenicity of porcine tissue, ultimately leading to xenograft rejection. METHODS: The N-glycome and glycosphingolipidome of native and decellularized porcine pericardia from wildtype (WT), GGTA1-KO and GGTA1/CMAH-KO pigs were analyzed by multiplexed capillary gel electrophoresis coupled to laser-induced fluorescence detection. RESULTS: We identified biantennary and core-fucosylated N-glycans terminating with immunogenic α-Gal- and α-Gal-/Neu5Gc-epitopes on pericardium of WT pigs that were absent in GGTA1 and GGTA1/CMAH-KO pigs, respectively. Levels of N-glycans terminating with galactose bound in ß(1-4)-linkage to N-acetylglucosamine and their derivatives elongated by Neu5Ac were increased in both KO groups. N-glycans capped with Neu5Gc were increased in GGTA1-KO pigs compared to WT, but were not detected in GGTA1/CMAH-KO pigs. Similarly, the ganglioside Neu5Gc-GM3 was found in WT and GGTA1-KO but not in GGTA1/CMAH-KO pigs. The applied detergent based decellularization efficiently removed GSL glycans. CONCLUSION: Genetic deletion of GGTA1 or GGTA1/CMAH removes specific epitopes providing a more human-like glycosylation pattern, but at the same time changes distribution and levels of other porcine glycans that are potentially immunogenic.

Water-Energy-Carbon Nexus: Greenhouse Gas Emissions from Integrated Urban Drainage Systems in China.

Greenhouse gas (GHG) emissions from integrated urban drainage systems (IUDSs), including sewer, wastewater treatment plants (WWTPs), and receiving water systems, have not yet been integrated due to the lack of modeling tools. Here, we updated the computable general equilibrium-based System Dynamics and Water Environmental Model (CGE-SyDWEM), a recently developed model simulating the water-energy-carbon nexus at the watershed level, to calculate the direct and indirect (electricity use and external) GHG emissions from IUDSs considering carbon mitigation strategies and water engineering practices. The updated CGE-SyDWEM was applied to an estuary watershed in Shenzhen, the fourth largest city in China. With increasing socio-economic development and water infrastructure systems upgrading, GHG emissions are projected to increase from 129.2 (95% CI: 95.9-162.5) kt in 2007 to 190.7 (144.8-236.6) kt in 2025, with 89% from WWTPs (direct: 17%; electricity use: 65%; and external: 7%), 10% from the sewer (direct: 1% and electricity use: 9%) and 1% from receiving waters (direct). Carbon mitigation can reduce GHG emissions by 7% and emission intensity by 6% by 2025, with 63% contributed by external emission reduction from chemical uses. The integrated model can aid water, energy, and carbon decision-makers in finding cost-effective solutions for water and energy security in the future.

Global Impacts of a Bilateral Trade Policy on Ballast Water-Mediated Species Spread Risk: A Case Study of Sino-US Trade.

A trade policy could generate both economic and environmental impacts. This work is focused on the impacts of a bilateral trade policy on ballast water-mediated nonindigenous species (NIS) spread risk. Taking the hypothetical Sino-US trade restriction as an example, we integrate a computable general equilibrium model and a higher-order NIS spread risk assessment model to examine the impacts of bilateral trade policy on both the economy and NIS spread risks. We have two important findings. First, the Sino-US trade restriction would cause decreases in NIS spread risks to China and the US, as well as to three quarters of worldwide countries/regions. However, the rest one fourth would experience increased NIS spread risks. Second, the relationship between changes in exports and changes in NIS spread risks might not be directly proportional. This is observed with 46% of countries and regions that would see their exports increase but their NIS spread risks drop, with positive impacts on both their economies and environment under the Sino-US trade restriction. These results reveal both broader global impacts as well as the decoupled economic and ecological impacts of a bilateral trade policy. These broader impacts demonstrate the necessity for national governments, which are parties to bilateral agreements to give due consideration to the economic and environmental impacts on countries and regions outside of the agreement.

Analyzing indirect economic impacts of wildfire damages on regional economies.

This article estimates the economic impacts of wildfire damage on Korea's regional economies, developing an integrated disaster-economic system for Korea. The system is composed of four modules: an interregional computable general equilibrium (ICGE) model for the eastern mountain area (EMA) and the rest of Korea, a Bayesian wildfire model, a transportation demand model, and a tourist expenditure model. The model has a hierarchical structure, with the ICGE model serving as a core module to link to three other modules. In the impact analysis of a wildfire, three external shocks are injected into the ICGE model: (1) the wildfire damaged area derived from the Bayesian wildfire model, (2) changes in travel times among cities and counties derived from the transportation demand model, and (3) variations in visitors' expenditures derived from the tourist expenditure model. The simulation shows that the gross regional product (GRP) of the EMA would decrease by 0.25% to 0.55% without climate change and by 0.51%-1.23% with climate change. This article contributes to the development of quantitative linkages between macro and micro spatial models in a bottom-up system for the impact analysis of disasters, integrating a regional economic model with a place-based disaster model and the demands of tourism and transportation.

Hydrogen-rich gas production from disposable COVID-19 mask by steam gasification.

Globally, the demand for masks has increased due to the COVID-19 pandemic, resulting in 490,201 tons of waste masks disposed of per month. Since masks are used in places with a high risk of virus infection, waste masks retain the risk of virus contamination. In this study, a 1 kg/h lab-scale (diameter: 0.114 m, height: 1 m) bubbling fluidized bed gasifier was used for steam gasification (temperature: 800 °C, steam/carbon (S/C) ratio: 1.5) of waste masks. The use of a downstream reactor with activated carbon (AC) for tar cracking and the enhancement of hydrogen production was examined. Steam gasification with AC produces syngas with H2, CO, CH4, and CO2 content of 38.89, 6.40, 21.69, and 7.34 vol%, respectively. The lower heating value of the product gas was 29.66 MJ/Nm3 and the cold gas efficiency was 74.55 %. This study showed that steam gasification can be used for the utilization of waste masks and the production of hydrogen-rich gas for further applications.

Feed-in tariffs and the carbon emission trading scheme under China's peak emission target: A dynamic CGE analysis for the development of renewable electricity.

Thermal power industry is one of China's leading sources of carbon emissions. China has launched a national carbon emissions trading scheme (ETS) and renewable energy incentive programs to achieve its peak emission target by 2030. However, since 2021, China no longer provides a central feed-in tariff (FIT) for new centrally located solar photovoltaic (PV) power plants, commercial and industrially distributed PV projects, and newly approved onshore wind power projects. This change in policy may threaten China's carbon reduction targets and economic development. Using a dynamic computable general equilibrium (CGE) model, we assess the combined effects of carbon ETS and FIT on China's electricity sector, carbon emission peak target, renewable energy and economic development. In terms of policy overlap and integration, we analyze the impact of these policies and estimate how to coordinate FIT and carbon ETS policies to ensure their effectiveness. Results show that the overall effects of FIT subsidies are superior to phasing-out FIT scenarios. The fiscal pressure caused by FIT is lower than its actual expenditure because it stimulates economic activity and boosts government revenue. However, considering the multiplier effect of the FIT on promoting government revenue growth and GDP growth, the most effective FIT should be terminated in 2025, followed by subsidies ending in 2030 and 2035.

Impact of carbon border adjustment mechanism on China's manufacturing sector: A dynamic recursive CGE model based on an evolutionary game.

As the global carbon emission problem is getting more and more serious, the European Union has proposed the Carbon Border Adjustment Mechanism (CBAM) to prevent carbon leakage, which will have an impact on China's foreign trade. Based on this background and the problems of current research that ignores factors such as commodity prices, long-term impacts, intertemporal substitution analysis, and changes in national strategies for foreign exports, this paper propose a Computable General Equilibrium (CGE) model based on an evolutionary game as a dynamic recursive basis to study the impact of the CBAM on the Chinese manufacturing industry. For the industries mentioned in the CBAM, 18 affected sectors are collated, and a CGE model containing multiple blocks such as production, trade, and carbon emissions is built. Meanwhile, we establish an evolutionary game model with EU suppliers, manufacturers, and the government, allowing Chinese suppliers to compete with EU suppliers. Based on the above model, the impact of carbon tariff policies from 2020 to 2050 is studied. The results indicate that under the intra-EU competition condition, carbon tariffs will reduce the price of Chinese exports and slightly decrease China's real GDP, as well as the carbon emission intensity of 18 sectors and fossil energy. However, the impact of carbon tariffs on overall carbon emissions is small and is essentially a protective policy. In addition, the evolutionary game-based CGE model takes into account the dynamic strategies of both sides and is therefore less affected by carbon tariff shocks and recovers more quickly and more realistically. Finally, the article argues that the advantage of carbon tariffs for local suppliers is unsustainable and Chinese suppliers will still dominate, and local suppliers need more subsidies from the EU government. On the other hand, the Chinese government needs to implement a stricter carbon tax regime and export subsidies to improve the competitiveness of Chinese products in terms of green levels and price advantages. The purpose of this paper is to examine the quantitative impacts of CBAM on China's related manufacturing industries and strategies to maximize the benefits to both governments.

The individual and combined impact of environmental taxes in Chile - A flexible computable general equilibrium analysis.

Many studies simulate carbon taxes with computable general equilibrium (CGE) models, but there is scarce evidence about how other environmental taxes implemented simultaneously reinforce or lessen the impacts. This study aims to determine the individual and combined effect of taxes on CO2 and other local air pollutants (SO2, NOX, and PM) currently applied in Chile. A flexible CGE model is used to sensitize the results, allowing two nested production structures to be compared. Both nested production structures include a high disaggregation of the energy sector that considers different fossil fuels and renewable energies. The results show that environmental taxes reduce between 5.4% and 6.9% of net CO2 equivalent emissions in the most realistic scenarios. In addition, the carbon tax explains 84%-85% of the drop in net CO2 equivalent emissions, 81%-82% of the reduction in fossil energy consumption, 76%-78% of the decline in GDP, and generates co-benefits by reducing local air pollutants. The tax on PM emissions is the second more relevant to reduce net CO2 equivalent emissions, while taxes on SO2 and NOX emissions have marginal effects. By comparing the impacts of both structures to previous studies based on microdata, it is concluded that the KL-EM provides the best results.

Comparing the impacts of carbon tax and carbon emission trading, which regulation is more effective?

While many literatures have examined the influence of environmental regulation policy, which environmental regulation policy is more effective is still controversial. Taking China and two different economic regions as samples, we explore the effect of two popular environmental regulation policies, that is carbon tax and carbon emission trading, by a multi-regional environmental dynamic computable general equilibrium model. The results show that for the economic development, the carbon emission trading outperforms the carbon tax for the carbon emission trading will generate the lower economic cost. But for the emission reductions, the carbon tax outperforms the carbon emission trading for the total emissions from 2020 to 2030 are smallest when introducing carbon tax policy. We further study the effect of environmental regulation on different industries. It is found that the environmental regulation has a more obvious effect on energy industry, heavy industry and transport service industry.

Climate co-benefits of VOC control policies in China based on a cross-scale approach.

Volatile organic compounds (VOC) contributing to smog formation, have been an important indicator of atmospheric governance during China's "14th Five-Year Plan". VOC would be possibly incorporated into the scope of environmental protection tax, but previous studies have seldom explored impacts of VOC control policies at national and regional levels. Here, we design a national uniform VOC control policy, as well as two regionally differentiated policies based on regional disparities in PM2.5 concentrations and energy intensity by using a cross-scale dynamic computable general equilibrium (CGE) model. Our analysis is to assess the impacts of these policies on VOC, CO2, sulfur dioxide (SO2), nitrogen oxides (NOX), and PM2.5 emissions, air quality and environmental equity, and to estimate health benefits, policy costs and net benefits. We find that national and regionally differentiated VOC control policies generally lead to VOC emission reductions and generate co-benefits on emission reductions in CO2, SO2, NOX and PM2.5 at national and provincial levels. However, regional emission leakage exists due to differences in the provincial costs of VOC mitigation. The regionally differentiated VOC pricing policies are found to be more effective to enhance environmental equity than the uniform policy. In particular, the regionally differentiated VOC control policy based on provincial energy efficiency is found to be superior to other policies in terms of improve air quality. Furthermore, the human health benefits associated with VOC pricing policies would partially offset policy costs at both the national and regional levels. Our results suggest that policymakers would pay attention to developing regions with low energy efficiency which have the great emission reduction potential. Advanced producing technology and further end-of-pipe control measures to reduce non-combustion PM2.5 emissions are needed. VOC policy designed based on provincial energy efficiency provides great insights for environmental policy making to accomplish 2035 goal of building a Beautiful China.

Macroeconomic consequences of the COVID-19 pandemic.

We estimate the economic impacts of COVID-19 in the U.S. using a disaster economic consequence analysis framework implemented by a dynamic computable general equilibrium (CGE) model. This facilitates identification of relative influences of several causal factors as "shocks" to the model, including mandatory business closures, disease spread trajectories, behavioral responses, resilience, pent-up demand, and government stimulus packages. The analysis is grounded in primary data on avoidance behavior and healthcare parameters. The decomposition of the influence of various causal factors will help policymakers offset the negative influences and reinforce the positive ones during the remainder of this pandemic and future ones.

Serum N-glycomics of a novel CDG-IIb patient reveals aberrant IgG glycosylation.

Rare genetic mutations of the mannosyl-oligosaccharide glucosidase (MOGS) gene affecting the function of the mannosyl-oligosaccharide glucosidase (glucosidase I) are the cause of the congenital disorder of glycosylation IIb (CDG-IIb). Glucosidase I specifically removes the distal α1,2-linked glucose from the protein bound precursor N-glycan Glc3Man9GlcNAc2, which is the initial step of N-glycan maturation. Here, we comparatively analyzed N-glycosylation of the whole serum proteome, serum-derived immunoglobulin G (IgG), transferrin (TF), and α-1-antitrypsin (AAT) of a female patient who is compound heterozygous for 2 novel missense mutations in the MOGS gene, her heterozygous parents, and a sibling with wildtype genotype by multiplexed capillary gel electrophoresis coupled to laser induced fluorescence detection (xCGE-LIF) at unprecedented depth. Thereby, we detected the CDG-IIb-characteristic non-de-glucosylated N-glycans Glc3Man7-9GlcNAc2 as well as the free tetrasaccharide Glc3-Man in whole serum of the patient but not in the other family members. The N-glycan analysis of the serum proteome further revealed that relative intensities of IgG-specific complex type di-antennary N-glycans with core-fucosylation were considerably reduced in the patient's serum whereas TF- and AAT-characteristic sialylated di- and tri-antennary N-glycans were increased. This finding reflected the hypogammaglobulinemia diagnosed in the patient. We further detected aberrant oligo-mannose (Glc3Man7GlcNAc2) and hybrid type N-glycans on patient-derived IgGs and we attributed this defective glycosylation to be the reason for an increased IgG clearance. This mechanism can explain the hypogammaglobulinemia that is associated with CDG-IIb.