Multiplex Detection of Foodborne Pathogens using 3D Nanostructure Swab and Deep Learning-Based Classification of Raman Spectra.

Proactive management of foodborne illness requires routine surveillance of foodborne pathogens, which requires developing simple, rapid, and sensitive detection methods. Here, a strategy is presented that enables the detection of multiple foodborne bacteria using a 3D nanostructure swab and deep learning-based Raman signal classification. The nanostructure swab efficiently captures foodborne pathogens, and the portable Raman instrument directly collects the Raman signals of captured bacteria. a deep learning algorithm has been demonstrated, 1D convolutional neural network with binary labeling, achieves superior performance in classifying individual bacterial species. This methodology has been extended to mixed bacterial populations, maintaining accuracy close to 100%. In addition, the gradient-weighted class activation mapping method is used to provide an investigation of the Raman bands for foodborne pathogens. For practical application, blind tests are conducted on contaminated kitchen utensils and foods. The proposed technique is validated by the successful detection of bacterial species from the contaminated surfaces. The use of a 3D nanostructure swab, portable Raman device, and deep learning-based classification provides a powerful tool for rapid identification (≈5 min) of foodborne bacterial species. The detection strategy shows significant potential for reliable food safety monitoring, making a meaningful contribution to public health and the food industry.

The clinical relevance of a polygenic risk score for type 2 diabetes mellitus in the Korean population.

The clinical utility of a type 2 diabetes mellitus (T2DM) polygenic risk score (PRS) in the East Asian population remains underexplored. We aimed to examine the potential prognostic value of a T2DM PRS and assess its viability as a clinical instrument. We first established a T2DM PRS for 5490 Korean individuals using East Asian Biobank data (269,487 samples). Subsequently, we assessed the predictive capability of this T2DM PRS in a prospective longitudinal study with baseline data and data from seven additional follow-ups. Our analysis showed that the T2DM PRS could predict the transition of glucose tolerance stages from normal glucose tolerance to prediabetes and from prediabetes to T2DM. Moreover, T2DM patients in the top-decile PRS group were more likely to be treated with insulin (hazard ratio = 1.69, p value = 2.31E-02) than were those in the remaining PRS groups. T2DM PRS values were significantly high in the severe diabetes subgroup, characterized by insulin resistance and ß -cell dysfunction (p value = 0.0012). The prediction models with the T2DM PRS had significantly greater Harrel's C-indices than did corresponding models without it. By utilizing prospective longitudinal study data and extensive clinical risk factor information, our analysis provides valuable insights into the multifaceted clinical utility of the T2DM PRS.

Therapeutic potential of AAV-FL-Klotho in obesity: Impact on weight loss and lipid metabolism in mice.

Klotho, an anti-aging protein, has gained attention for its protective effects against various diseases, including metabolic disorders, through recombinant Klotho administration. However, the potential of Klotho as a target for gene therapy requires further exploration, as it remains relatively understudied in the context of metabolic disorders. In this study, we demonstrate that AAV-full length(FL)-Klotho administration induces weight loss in mice and provides protection against high-fat diet (HFD)-induced obesity and hepatic steatosis, concurrently reducing the weights of white adipose tissue and liver. AAV-FL-Klotho administration also enhanced thermogenic gene expression in brown adipose tissue (BAT) and improved the morphology of interscapular BAT. The weight loss effect of AAV-FL-Klotho was found to be, at least in part, mediated by UCP1-dependent thermogenesis in brown adipocytes, potentially influenced by hepatokines secreted from AAV-FL-Klotho-transduced hepatocytes. These findings suggest that AAV-FL-Klotho is an attractive candidate for gene therapy to combat obesity. Nevertheless, unbiased experiments have also revealed disturbances in lipid metabolism due to AAV-FL-Klotho, as evidenced by the emergence of lipomas and increased expression of hepatic lipogenic proteins.

NG ,NG -Dimethylarginine Dimethylaminohydrolase 1 Expression Is Dispensable for Cold- or Diet-Induced Thermogenesis.

The strategy to activate thermogenic adipocytes has therapeutic potential to overcome obesity as they dissipate surplus energy as heat through various mechanisms. NG,NG-dimethylarginine dimethylaminohydrolases (DDAHs) are enzymes involved in the nitric oxide-protein kinase G signaling axis which increases thermogenic gene expression. However, the role of DDAHs in thermogenic adipocytes has not been elucidated. The adipocyte-specific Ddah1 knockout mice are generated by crossing Ddah1fl/fl mice with adiponectin Cre recombinase mice. Adipocyte-specific DDAH1 overexpressing mice are generated using adeno-associated virus-double-floxed inverse open reading frame (AAV-DIO) system. These mice are analyzed under basal, cold exposure, or high-fat diet (HFD) conditions. Primary inguinal white adipose tissue cells from adipocyte-specific Ddah1 knockout mice expressed comparable amounts of Ucp1 mRNA. Adipocyte-specific DDAH1 overexpressing mice do not exhibit enhanced activation of thermogenic adipocytes. In addition, when these mice are exposed to cold environment or fed an HFD, their body temperature/weight and thermogenesis-related gene and protein expressions are unchanged. These findings indicate that DDAH1 does not play a role in either cold- or diet-induced thermogenesis. Therefore, adipocyte targeting DDAH1 gene therapy for the treatment of obesity is unlikely to be effective.

AAV-mediated skeletal muscle specific irisin expression does not contribute to weight loss in mice.

Obesity, a chronic disease, significantly increases the risk of various diseases, including diabetes, cardiovascular diseases, and cancers. Exercise is crucial for weight management not only through energy expenditure by muscle activity but also through stimulating the secretion of myokines, which affect various tissues. Irisin, derived from the proteolytic processing of fibronectin type III domain-containing protein 5 (Fndc5), is a well-studied myokine with beneficial effects on metabolism. This study explored the feasibility of adeno-associated virus (AAV)-mediated Fndc5 gene therapy to treat obesity in a mouse model using the AAV-DIO system to express Fndc5 specifically in skeletal muscle, and investigated its anti-obesity effect. Although Fndc5 was specifically expressed in the muscle, no significant impact on body weight under normal chow or high-fat diets was observed, and no change in thermogenic gene expression in inguinal white adipose tissue was detected. Notably, Fndc5 transduction did affect bone metabolism, consistent with previous reports. These findings suggest that AAV-mediated Fndc5 gene therapy may not be an efficient strategy for obesity, contrary to our expectations. Further research is needed to elucidate the complex mechanisms involved in irisin's role in obesity and related disorders.

Multicomponent Covalent Organic Framework Solid Electrolyte Allowing Effective Li-Ion Dissociation and Diffusion for All-Solid-State Batteries.

Organic solid electrolytes compatible with all-solid-state Li metal batteries (LMBs) are essential to ensuring battery safety, high energy density, and long-term cycling performance. However, it remains a challenge to develop an approach to provide organic solid electrolytes with capabilities for the facile dissociation of strong Li-ion pairs and fast transport of ionic components. Herein, a diethylene glycol-modified pyridinium covalent organic framework (DEG-PMCOF) with a well-defined periodic structure is prepared as a multicomponent solid electrolyte with a cationic moiety of high polarity, an additional flexible ion-transporter, and an ordered ionic channel for all-solid-state LMBs. The DEG-containing pyridinium groups of DEG-PMCOF allow a lower dissociation energy of Li salts and a smaller energy barrier of Li-ion transport, leading to high ion conductivity (1.71 × 10-4 S cm-1) and a large Li-ion transfer number (0.61) at room temperature in the solid electrolyte. The DEG-PMCOF solid electrolyte exhibits a wide electrochemical stability window and effectively suppresses the formation of Li dendrites and dead Li in all-solid-state LMBs. Molecular dynamics and density functional theory simulations provide insights into the mechanisms for the enhanced Li-ion transport driven by the integrated diffusion process based on hopping motion, vehicle motion, and free diffusion of DEG-PMCOF. The all-solid-state LMB assembled with a DEG-PMCOF solid electrolyte displays a high specific capacity with a retention of 99% and an outstanding Coulombic efficiency of 99% at various C-rates during long-term cycling. This DEG-PMCOF approach can offer an effective route to design various solid-state Li batteries.

Machine learning-based inverse design methods considering data characteristics and design space size in materials design and manufacturing: a review.

In the last few decades, the influence of machine learning has permeated many areas of science and technology, including the field of materials science. This toolkit of data driven methods accelerated the discovery and production of new materials by accurately predicting the complicated physical processes and mechanisms that are not fully described by existing materials theories. However, the availability of a growing number of increasingly complex machine learning models confronts us with the question of "which machine learning algorithm to employ". In this review, we provide a comprehensive review of common machine learning algorithms used for materials design, as well as a guideline for selecting the most appropriate model considering the nature of the design problem. To this end, we classify the material design problems into four categories of: (i) the training data set being sufficiently large to capture the trend of design space (interpolation problem), (ii) a vast design space that cannot be explored thoroughly with the initial training data set alone (extrapolation problem), (iii) multi-fidelity datasets (small accurate dataset and large approximate dataset), and (iv) only a small dataset available. The most successful machine learning-based surrogate models and design approaches will be discussed for each case along with pertinent literature. This review focuses mostly on the use of ML algorithms for the inverse design of complicated composite structures, a topic that has received a lot of attention recently with the rise of additive manufacturing.

Cold-induced adaptive thermogenesis is impaired by exposure of Asian sand dust in mice.

Desertification and desert sandstorms caused by the worsening global warming pose increasing risks to human health. In particular, Asian sand dust (ASD) exposure has been related to an increase in mortality and hospital admissions for respiratory diseases. In this study, we investigated the effects of ASD on metabolic tissues in comparison to diesel particulate matter (DPM) that is known to cause adverse health effects. We found that larger lipid droplets were accumulated in the brown adipose tissues (BAT) of ASD-administered but not DPM-administered mice. Thermogenic gene expression was decreased in these mice as well. When ASD-administered mice were exposed to the cold, they failed to maintain their body temperature, suggesting that the ASD administration had led to impairments in cold-induced adaptive thermogenesis. However, impaired thermogenesis was not observed in DPM-administered mice. Furthermore, mice fed a high-fat diet that were chronically administered ASD demonstrated unexplained weight loss, indicating that chronic administration of ASD could be lethal in obese mice. We further identified that ASD-induced lung inflammation was not exacerbated in uncoupling protein 1 knockout mice, whose thermogenic capacity is impaired. Collectively, ASD exposure can impair cold-induced adaptive thermogenic responses in mice and increase the risk of mortality in obese mice.

Preferential dissolution behaviour of the austenite phase in Fe-27Cr-xC high chromium cast iron.

Preferential dissolution behaviour of the austenite (γ) phase in Fe-27Cr-xC high chromium cast irons (HCCIs) immersed in 0.1 mol dm-3 H2SO4 + 0.05 mol dm-3 HCl was investigated. Potentiodynamic and potentiostatic polarisation revealed that the primary and eutectic γ phases dissolved preferentially at -0.35 and 0.00 VSilver Silverchloride Electrode potential in sat. KCl (SSE), respectively. The immersion of the HCCIs in the solution showed that the dissolution of the primary γ phase dominated for ca. 1 h, while the primary and eutectic γ phases dissolved after ca. 1 h. However, the carbide phases remained undissolved during the dissolution of the γ phases. Furthermore, the corrosion rate of the HCCIs increased with the increasing C content owing to the increase in the contact potential difference values of the γ and carbide phases. The change in electromotive force due to C addition was related to the accelerated corrosion rate of the γ phases.

An Ion-Channel-Restructured Zwitterionic Covalent Organic Framework Solid Electrolyte for All-Solid-State Lithium-Metal Batteries.

Organic solid electrolytes offer an effective route for safe and high-energy-density all-solid-state Li metal batteries. However, it remains a challenge to devise a new strategy to promote the dissociation of strong ion pairs and the transport of ionic components in organic solid electrolytes. Herein, a zwitterionic covalent organic framework (Zwitt-COF) with well-defined chemical and pore structures is prepared as a solid electrolyte capable of accelerating the dissociation and transport of Li ions. The Zwitt-COF solid electrolyte exhibits a high room-temperature ionic conductivity of 1.65 × 10-4  S cm-1 with a wide electrochemical stability window. Besides, the Zwitt-COF solid electrolyte displays stable Li plating/stripping behavior via effective inhibition of the formation of Li dendrites and dead Li, leading to superior long-term cycle performance with retention of 99% discharge capacity and 98% Coulombic efficiency in an all-solid-state Li-metal battery. Theoretical simulations reveal that the incorporation of zwitterionic groups into COF can facilitate the dissociation of strong ion pairs and reconstruct the AA-stacking configuration by dissociative adsorption of Li+ ions on Zwitt-COF producing linear hexagonal ion channels in the Zwitt-COF solid electrolyte. This strategy based on Zwitt-COF can provide an alternative way to construct various solid-state Li batteries.

Effects of hydrothermal pretreatment on methane potential of anaerobic digestion sludge cake of cattle manure containing sawdust as bedding materials.

OBJECTIVE: The purpose of this study was to analyze the effect of the hydrothermal pretreat-ment of anaerobic digestion sludge cake (ADSC) of cattle manure on the solubilization of organic matter and the methane yield to improve the anaerobic digestion efficiency of cattle manure collected from the sawdust pens of cattle. METHODS: Anaerobic digestion sludge cake of cattle manure was thermally pretreated at 160°C, 180°C, 200°C, and 220°C by a hydrothermal pressure reactor, and the biochemical methane potential of ADSC hydrolysate was analyzed. Methane yield recovered by the hydrothermal pretreatment of ADCS was estimated based on mass balance. RESULTS: The chemical oxygen demand solubilization degree (CODs) of the hydrothermal hydrolysate increased to 63.56%, 67.13%, 70.07%, and 66.14% at the hydrothermal reaction temperatures of 160°C, 180°C, 200°C, and 220°C, respectively. Considering the volatile solids content obtained after the hydrothermal pretreatment, the methane of 10.2 Nm3/ton-ADSC was recovered from ADSC of 1.0 ton, and methane yields of ADSC hydrolysate increased to 15.6, 18.0, 17.4, and 17.2 Nm3/ton-ADSC. CONCLUSION: Therefore, the optimal hydrothermal reaction temperature that yielded the maximum methane yield was 180°C based on mass balance, and the methane yield from cattle manure containing sawdust was improved by the hydrothermal pretreatment of ADSC.

Investigation of genetic variants and causal biomarkers associated with brain aging.

Delta age is a biomarker of brain aging that captures differences between the chronological age and the predicted biological brain age. Using multimodal data of brain MRI, genomics, and blood-based biomarkers and metabolomics in UK Biobank, this study investigates an explainable and causal basis of high delta age. A visual saliency map of brain regions showed that lower volumes in the fornix and the lower part of the thalamus are key predictors of high delta age. Genome-wide association analysis of the delta age using the SNP array data identified associated variants in gene regions such as KLF3-AS1 and STX1. GWAS was also performed on the volumes in the fornix and the lower part of the thalamus, showing a high genetic correlation with delta age, indicating that they share a genetic basis. Mendelian randomization (MR) for all metabolomic biomarkers and blood-related phenotypes showed that immune-related phenotypes have a causal impact on increasing delta age. Our analysis revealed regions in the brain that are susceptible to the aging process and provided evidence of the causal and genetic connections between immune responses and brain aging.

Standards for recognition and approval rate of occupational cerebro-cardiovascular diseases in Korea.

Background: Although working hours have decreased in Korea, they are still high compared to that of other countries. In Korea, cardiovascular and cerebrovascular diseases (CCVDs) related to overwork in Korea continually occur, and the social burden from overwork is estimated to be high. This study investigated the amendment of regulations affecting the approval rate of occupational CCVDs. Methods: The change in approval rate of occupational CCVDs and related regulations were investigated using the Act and public notice on the standards for recognition of occupational CCVDs and the yearbooks of the Ministry of Employment and Labor. The CCVD mortality was estimated using data on the number of deaths according to the cause of death, the number of employed people, and resident registration population aged 15-64 years. The cumulative mortality of CCVDs was estimated using the Kaplan-Meier method. Results: Since the establishment of the standards for recognition in Korea in 1982, the scope of occupational diseases has been expanded to include intracerebral hemorrhage, subarachnoid hemorrhage, cerebral infarction, myocardial infarction, and aortic dissection. In 2013, the concept of working hours was introduced in chronic overwork. The approval rate of occupational CCVDs was 44.7% in 2006, which decreased to 12.9% in 2011. After the improvement of related regulations, the approval rate increased to 41.3% in 2018. From 2000 to 2017, the CCVD mortality of both the unemployed and employed tended to decrease, and their cumulative CCVD mortalities were 549.3 and 319.7 per 100,000 people, respectively. Conclusions: CCVDs are recognized as occupational diseases in Korea. The amendments to the standards for recognition, the introduction of the Occupational Disease Adjudication Committee, the principle of presumption, and the reduction of working hours have changed the approval rate of occupational CCVDs. A strategic approach is needed to further reduce the incidence of CCVDs.

Deep neural network-based structural health monitoring technique for real-time crack detection and localization using strain gauge sensors.

Structural health monitoring (SHM) techniques often require a large number of sensors to evaluate and monitor the structural health. In this paper, we propose a deep neural network (DNN)-based SHM method for accurate crack detection and localization in real time using a small number of strain gauge sensors and confirm its feasibility based on experimental data. The proposed method combines a DNN model with principal component analysis (PCA) to predict the strain field based on the local strains measured by strain gauge sensors located rather sparsely. We demonstrate the potential of the proposed technique via a cyclic 4-point bending test performed on a composite material specimen without cracks and seven specimens with different lengths of cracks. A dataset containing local strains measured with 12 strain gauge sensors and strain field measured with a digital image correlation (DIC) device was prepared. The strain field dataset from DIC is converted to a smaller dimension latent space with a few eigen basis via PCA, and a DNN model is trained to predict principal component values of each image with 12 strain gauge sensor measurements as input. The proposed method turns out to accurately predict the strain field for all specimens considered in the study.

Efficacy and Safety of COVID-19 Treatment Using Convalescent Plasma Transfusion: Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials.

This study investigated the efficacy and safety of convalescent plasma (CP) transfusion against the coronavirus disease 2019 (COVID-19) via a systematic review and meta-analysis of randomized controlled trials (RCTs). A total of 5467 articles obtained from electronic databases were assessed; however, only 34 RCTs were eligible after manually screening and eliminating unnecessary studies. The beneficial effect was addressed by assessing the risk ratio (RR) and standardized mean differences (SMDs) of the meta-analysis. It was demonstrated that CP therapy is not effective in improving clinical outcomes, including reducing mortality with an RR of 0.88 [0.76; 1.03] (I2 = 68% and p = 0.10) and length of hospitalization with SMD of -0.47 [-0.95; 0.00] (I2 = 99% and p = 0.05). Subgroup analysis provided strong evidence that CP transfusion does not significantly reduce all-cause mortality compared to standard of care (SOC) with an RR of 1.01 [0.99; 1.03] (I2 = 70% and p = 0.33). In addition, CP was found to be safe for and well-tolerated by COVID-19 patients as was the SOC in healthcare settings. Overall, the results suggest that CP should not be applied outside of randomized trials because of less benefit in improving clinical outcomes for COVID-19 treatment.

Cohort Profile: Gachon Regional Occupational Cohort Study (GROCS).

Background/Aims: The Gachon Regional Occupational Cohort Study (GROCS) is a large-scale longitudinal study of occupational safety and health data (covering Work Environment Monitoring, Workers' Health Surveillance, and Occupational Health Service) conducted by the Gachon University Gil Medical Center (GUGMC) in Incheon, Republic of Korea. We conducted GROCS to identify the health effects of workers' occupational risks, behavior, socioeconomic status, and life style. Methods: The GROCS includes data from Work Environment Monitoring, Workers' Health Surveillance, and Occupational Health Service. The baseline year for all data collection was 2018. Work Environment Monitoring was conducted in 240 companies located in Incheon. General Health Examination and Special Health Examination were performed on 32,725 and 9,504 workers, respectively. Occupational Health Services were provided to 16,883 workers in 171 companies. These data have been collected and operated at an external data management institution and were provided as a retrospective cohort after removing personal identification information. Results: In 2018, the total number of companies was 2,854, among which which 488 special Health Examination, 171 Work Environment Monitoring, and 240 Occupational Health Service. The proportion of companies undergoing Special Health Examination was 17.1%, the proportion of companies undergoing Work Environment Monitoring was 8.4%, and the proportion of Companies undergoing Occupational Health Service was 6.0%. Conclusion: GROCS expects researchers to utilize its useful and reliable resource for occupational health and surveillance with for academic or political purposes to lead to improved workers' health and working environment.

Structural and Electronic Modulations of Imidazolium Covalent Organic Framework-Derived Electrocatalysts for Oxygen Redox Reactions in Rechargeable Zn-Air Batteries.

Covalent organic frameworks (COFs) are promising candidates for the controllable design of electrocatalysts. However, bifunctional electrocatalytic activities for the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) remain challenging in COFs. In this study, imidazolium-rich COFs (IMCOFs) with well-defined active sites and characteristic three-dimensional assembly structures were readily prepared, and their electronic structures were tuned by Co incorporation to elicit bifunctional electrocatalytic activities for the ORR and OER. The Co nanoparticle-incorporated spherical IMCOF-derived electrocatalyst (CoNP-s-IMCOF) exhibited lower overpotentials for the ORR and OER compared with the atomic Co-incorporated planar IMCOF-derived electrocatalyst (Co-p-IMCOF). Computational simulations revealed that the imidazole carbon sites of CoNP-s-IMCOF rather than the triazine carbons were the active sites for the ORR and OER, and its p-band center downshifted via charge transfer, facilitating the chemisorption of oxygen intermediates during the reactions. A Zn-air battery with CoNP-s-IMCOF exhibited a small voltage gap of 1.3 V with excellent durability for 935 cycles. This approach for control over the three-dimensional assembly and electronic structures of IMCOFs can be extended to the development of diverse catalytic nanomaterials for applications of interest.

Analysis of self-reported mental health problems among the self-employed compared with paid workers in the Republic of Korea.

Background: As self-employed workers are vulnerable to health problems, this study aimed to analyze mental health problems and sleep disturbances among self-employed workers compared with paid workers in Korea. Methods: A total of 34,750 workers (23,938 paid workers and 10,812 self-employed workers) were analyzed from the fifth Korean Working Condition Survey, which included 50,205 households collected by stratified sampling in 2017. To compare mental health problems and sleep disturbance among self-employed workers and paid workers, multivariate logistic regression analyses were performed. Results: The odds ratio in self-employed workers compared with paid workers was 1.25 (95% confidence interval [CI]: 1.09-1.42) for anxiety, 1.11 (95% CI: 1.04-1.17) for overall fatigue, 1.11 (95% CI: 1.04-1.20) for difficulty falling asleep, 1.10 (95% CI: 1.02-1.18) for difficulty maintaining sleep and 1.24 (95% CI: 1.16-1.32) for extreme fatigue after waking up. Conclusions: Self-employed workers in Korea have a higher risk of self-reported mental health problems and sleep disturbances than paid workers. Further studies with a longitudinal design and structured evaluation are required to investigate the causal relationship between health problems and self-employment.

Modulating the electrocatalytic activity of N-doped carbon frameworks via coupling with dual metals for Zn-air batteries.

N-Doped carbon electrocatalysts are a promising alternative to precious metal catalysts to promote oxygen reduction reaction (ORR). However, it remains a challenge to design the desired active sites on carbon skeletons in a controllable manner for ORR. Herein, we developed a facile approach based on oxygen-mediated solvothermal radical reaction (OSRR) for preparation of N-doped carbon electrocatalysts with a pre-designed active site and modulated catalytic activity for ORR. In the OSRR, 2-methylimidazole reacted with Co and Mn salts to form an active site precursor (MnCo-MIm) in N-methyl-2-pyrrolidone (NMP) at room temperature. Then, the reaction temperature increased to 140 °C under an oxygen atmosphere to generate NMP radicals, followed by their polymerization with the pre-formed MnCo-MIm to produce Mn-coupled Co nanoparticle-embedded N-doped carbon framework (MnCo-NCF). The MnCo-NCF showed uniform dispersion of nitrogen atoms and Mn-doped Co nanoparticles on the carbon skeleton with micropores and mesopores. The MnCo-NCF exhibited higher electrocatalytic activity for ORR than did a Co nanoparticle only-incorporated carbon framework due to the improved charge transfer from the Mn-doped Co nanoparticles to the carbon skeleton. In addition, the Zn-air battery assembled with MnCo-NCF had superior performance and durability to the battery using commercial Pt/C. This facile approach can be extended for designing carbon electrocatalysts with desired active sites to promote specific reactions.

Non-invasive administration of AAV to target lung parenchymal cells and develop SARS-CoV-2-susceptible mice.

Adeno-associated virus (AAV)-mediated gene delivery holds great promise for gene therapy. However, the non-invasive delivery of AAV for lung tissues has not been adequately established. Here, we revealed that the intratracheal administration of an appropriate amount of AAV2/8 predominantly targets lung tissue. AAV-mediated gene delivery that we used in this study induced the expression of the desired protein in lung parenchymal cells, including alveolar type II cells. We harnessed the technique to develop severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-susceptible mice. Three kinds of immune function-relevant gene knockout (KO) mice were transduced with AAV encoding human angiotensin-converting enzyme 2 (hACE2) and then injected with SARS-CoV-2. Among these mice, type I interferon receptor (IFNAR) KO mice showed increased viral titer in the lungs compared to that in the other KO mice. Moreover, nucleocapsid protein of SARS-CoV-2 and multiple lesions in the trachea and lung were observed in AAV-hACE2-transduced, SARS-CoV-2-infected IFNAR KO mice, indicating the involvement of type I interferon signaling in the protection of SARS-CoV-2. In this study, we demonstrate the ease and rapidness of the intratracheal administration of AAV for targeting lung tissue in mice, and this can be used to study diverse pulmonary diseases.