Miracle-dz/UniFAR-FTUs huggingface dataset:
The K18-hACE2 Transgenic Mouse Model Recapitulates Non-Severe and Severe COVID-19 in Response to Infectious Dose of SARS-CoV-2 Virus

A comprehensive analysis and characterization of a SARS-CoV-2 infection model that mimics non-severe and severe COVID-19 in humans is warranted for understating the virus and developing preventive and therapeutic agents. Here, we characterized the K18-hACE2 mouse model expressing human (h)ACE2 in mice, controlled by the human keratin 18 (K18) promoter, in epithelia, including airway epithelial cells where SARS-CoV-2 infections typically start. We found that intranasal inoculation with higher viral doses (2×103 and 2×104 PFU) of SARS-CoV-2 caused lethality of all mice and severe damage of various organs, including lungs, liver, and kidney, while lower doses (2×101 and 2×102 PFU) led to less severe tissue damage and some mice recovered from the infection. In this humanized hACE2 mouse model, SARS-CoV-2 infection damaged multiple tissues, with a dose-dependent effect in most tissues. Similar damage was observed in biopsy samples from COVID-19 patients. Finally, the mice that recovered after infection with a low dose of virus also survived rechallenge with a high dose of virus. Compared to other existing models, the K18-hACE2 model seems to be the most sensitive COVID-19 model reported to date. Our work expands the information available about this model to include analysis of multiple infectious doses and various tissues with comparison to human biopsy samples from COVID-19 patients. In conclusion, the K18-hACE2 mouse model recapitulates both severe and non-severe COVID-19 in humans and can provide insight into disease progression and the efficacy of therapeutics for preventing or treating COVID-19. Importance The pandemic of COVID-19 has reached 112,589,814 cases and caused 2,493,795 deaths worldwide as of February 23, 2021, has raised an urgent need for development of novel drugs and therapeutics to prevent the spread and pathogenesis of SARS-CoV-2. To achieve this goal, an animal model that recapitulates the features of human COVID-19 disease progress and pathogenesis is greatly needed. In this study, we have comprehensively characterized a mouse model of SARS-CoV-2 infection using K18-hACE2 transgenic mice. We infected the mice with low and high doses of SARS-CoV-2 virus to study the pathogenesis and survival in response to different infection patterns. Moreover, we compared the pathogenesis of the K18-hACE2 transgenic mice with that of the COVID-19 patients to show that this model could be a useful tool for the development of anti-viral drugs and therapeutics.
Seafloor Geodesy From Repeated Multibeam Bathymetric Surveys: Application to Seafloor Displacement Caused by the 2011 Tohoku-Oki Earthquake

Repeated multibeam bathymetric surveys played an important role for understanding the distribution of coseismic seafloor displacement caused by the March 11, 2011 Mw 9.0 Tohoku-oki earthquake. After the earthquake, we collected bathymetric data along the same tracks obtained before the earthquake. The selected tracks were crossing the trench and extending from the landward to seaward trench slopes. We examined the seafloor displacement on the landward relative to the seaward by means of the difference in bathymetry before and after the earthquake. The multibeam bathymetric survey has the advantage of areal coverage. The repeated surveys clarified the areal distribution of the coseismic seafloor displacement. In the main rupture area, very large seafloor displacement was observed. Sharp bathymetric change at the trench axis provided solid evidence that the fault slip on the shallowest part of the megathrust reached the trench axis and peaked at the trench axis. The very large displacement is limited to the particular area. Smaller seafloor displacements were observed in the area tens of kilometers away from the main rupture area. We present methods and results of the repeated multibeam bathymetric surveys and an application to the seafloor displacement caused by the 2011 Tohoku-oki earthquake in the northern Japan Trench. Less than several meters in seafloor vertical displacements and less than 20 m in seafloor horizontal displacement were estimated in the northern Japan Trench. The estimated smaller displacements are comparable in magnitude to error of the seafloor displacement observation from our bathymetric survey. Nevertheless, three adjacent survey tracks showed coherent relative differences in seafloor elevation, which suggests the relative difference enables us to discuss the along-track variation in seafloor displacement in the area. However, our survey was affected by uncertainties of roll and pitch biases and sound velocity errors. Well-prepared repeated multibeam bathymetric survey for the purpose of seafloor geodesy could lead to a higher resolution and more accurate result. Repeated acquisition of high resolution and accuracy bathymetric data using state-of-the-art technology will be important to quantitative discussion of the seafloor displacements caused by even smaller magnitude earthquakes and tsunamis.
Chinese Herbal Medicines and Active Metabolites: Potential Antioxidant Treatments for Atherosclerosis

Atherosclerosis is a complex chronic disease that occurs in the arterial wall. Oxidative stress plays a crucial role in the occurrence and progression of atherosclerotic plaques. The dominance of oxidative stress over antioxidative capacity generates excess reactive oxygen species, leading to dysfunctions of the endothelium and accelerating atherosclerotic plaque progression. Studies showed that Chinese herbal medicines and traditional Chinese medicine (TCM) might regulate oxidative stress; they have already been used to treat diseases related to atherosclerosis, including stroke and myocardial infarction. This review will summarize the mechanisms of oxidative stress in atherosclerosis and discuss studies of Chinese herbal medicines and TCM preparations treating atherosclerosis, aiming to increase understanding of TCM and stimulate research for new drugs to treat diseases associated with oxidative stress.
Shaoyao-Gancao Decoction Ameliorates the Inflammation State in Polycystic Ovary Syndrome Rats via Remodeling Gut Microbiota and Suppressing the TLR4/NF-κB Pathway

Background: Emerging evidence suggests that gut microbiota plays a vital role in the occurrence of multiple endocrine disorders including polycystic ovary syndrome (PCOS). Shaoyao-Gancao Decoction (SGD), a classical Chinese prescription, has been widely used in the treatment of PCOS for decades. In previous studies, we found that SGD treatment could effectively reduce ovarian inflammation in PCOS rats. However, whether the anti-inflammation effect of SGD involves the regulation of the gut microbiota remains elusive. Methods: Letrozole-induced PCOS rat models were established, and the therapeutic effects of SGD were evaluated. Specifically, body weight, serum hormone concentrations, estrus phase and ovary histopathology were assessed. Then the structure of gut microbiota was determined by 16s rRNA sequencing. Additionally, the serum levels of pro-inflammatory cytokines and LPS were measured by ELISA kits. The key gene and protein expressions of TLR4/NF-κB signaling pathway were detected by quantitative real-time PCR and western blot. Results: SGD could effectively reduce body weight, regulate estrous cycles and ameliorate hyperandrogenism in PCOS rats. In addition, SGD treatment decreased releases of pro-inflammatory cytokines, enhanced the expressions of tight junction (occludin and claudin1), and then prevented a translocation of LPS into bloodstream. SGD could significantly reduce the ratio of Firmicutes to Bacteroidetes, decrease the abundance of LPS-producing pathogens Proteobateria and enrich the abundance of Butyricicoccus, Coprococcus, Akkermansia Blautia and Bacteroides in PCOS rats. Furthermore, SGD blunted the key gene and protein expressions of TLR4/NF-κB signaling pathway both in vivo and in LPS-induced RAW264.7 cells. Conclusion: SGD administration could ameliorate the inflammatory response in PCOS rats by remodeling gut microbiome structure, protecting gut barrier, and suppressing TLR4/NF-κB signaling pathway.
Low-Lying Electronic States of the Nickel Dimer

The generalized Van Vleck second order multireference perturbation theory (GVVPT2) method was used to investigate the low-lying electronic states of Ni2. Because the nickel atom has an excitation energy of only 0.025 eV to its first excited state (the least in the first row of transition elements), Ni2 has a particularly large number of low-lying states. Full potential energy curves (PECs) of more than a dozen low-lying electronic states of Ni2, resulting from the atomic combinations 3F4 + 3F4 and 3D3 + 3D3, were computed. In agreement with previous theoretical studies, we found the lowest lying states of Ni2 to correlate with the 3D3 + 3D3 dissociation limit, and the holes in the d-subshells were in the subspace of delta orbitals (i.e., the so-dubbed δδ-states). In particular, the ground state was determined as X 1Γg and had spectroscopic constants: bond length (R e) = 2.26 Å, harmonic frequency (ωe) = 276.0 cm−1, and binding energy (D e) = 1.75 eV; whereas the 1 1Σg + excited state (with spectroscopic constants: R e = 2.26 Å, ωe = 276.8 cm−1, and D e = 1.75) of the 3D3 + 3D3 dissociation channel lay at only 16.4 cm−1 (0.002 eV) above the ground state at the equilibrium geometry. Inclusion of scalar relativistic effects through the spin-free exact two component (sf-X2C) method reduced the bond lengths of both of these two states to 2.20 Å, and increased their binding energies to 1.95 eV and harmonic frequencies to 296.0 cm−1 for X 1Γg and 297.0 cm−1 for 1 1Σg +. These values are in good agreement with experimental values of R e = 2.1545 ± 0.0004 Å, ωe = 280 ± 20 cm−1, and D 0 = 2.042 ± 0.002 eV for the ground state. All states considered within the 3F4 + 3F4 dissociation channel proved to be energetically high-lying and van der Waals-like in nature. In contrast to most previous theoretical studies of Ni2, full PECs of all considered electronic states of the molecule were produced.
The Effect of Antihypertensive Medications on Testing for Primary Aldosteronism

Primary aldosteronism (PA) is a potentially curable form of secondary hypertension caused by excessive renin-independent aldosterone secretion, leading to increased target organ damage and cardiovascular morbidity and mortality. The diagnosis of PA requires measuring renin and aldosterone to calculate the aldosterone-to-renin ratio, followed by confirmatory tests to demonstrate renin-independent aldosterone secretion and/or PA subtype differentiation. Various antihypertensive drug classes interfere with the renin-angiotensin-aldosterone axis and hence evaluation for PA should ideally be performed off-drugs. This is, however, often precluded by the risks related to suboptimal control of blood pressure and serum potassium level in the evaluation period. In the present review, we summarized the evidence regarding the effect of various antihypertensive drug classes on biochemical testing for PA, and critically appraised the issue whether and which antihypertensive medications should be withdrawn or, conversely, might be continued in patients evaluated for PA. The least interfering drugs are calcium antagonists, alpha-blockers, hydralazine, and possibly moxonidine. If necessary, the testing may also be attempted during treatment with beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers but renin and aldosterone measurements must be interpreted in the context of known effects of these drugs on these parameters. Views are evolving on the feasibility of testing during treatment with mineralocorticoid receptor antagonists, as these drugs are now increasingly considered acceptable in specific patient subsets, particularly in those with severe hypokalemia and/or poor blood pressure control on alternative treatment.
Advanced treatment of actual textile dye wastewater by Fenton‐flocculation process

To improve the performance of actual textile dye wastewater treatment, an advanced treatment combining the Fenton and flocculation processes was developed. The parameters affecting decolorization in the Fenton-flocculation process, including initial pH, H2O2 dosage, Fe2+dosage, reaction temperature, reaction time, and flocculant dosage, were examined. With the optimal Fenton-flocculation condition parameters, more than 95 % COD removal, 99 % colour removal, and 99 % turbidity removal were obtained. UV-visible spectra of raw water and supernatant were further obtained after the Fenton-flocculation process, and results demonstrated that the chromophoric groups and the conjugated system in the dye molecular structure were destroyed. All these results confirmed that the Fenton-flocculation process was a favourable and effective post-treatment method for actual textile dye wastewater.
Distinct Roles of Hemocytes at Different Stages of Infection by Dengue and Zika Viruses in Aedes aegypti Mosquitoes

Aedes aegypti mosquitoes are vectors for arboviruses of medical importance such as dengue (DENV) and Zika (ZIKV) viruses. Different innate immune pathways contribute to the control of arboviruses in the mosquito vector including RNA interference, Toll and Jak-STAT pathways. However, the role of cellular responses mediated by circulating macrophage-like cells known as hemocytes remains unclear. Here we show that hemocytes are recruited to the midgut of Ae. aegypti mosquitoes in response to DENV or ZIKV. Blockade of the phagocytic function of hemocytes using latex beads induced increased accumulation of hemocytes in the midgut and a reduction in virus infection levels in this organ. In contrast, inhibition of phagocytosis by hemocytes led to increased systemic dissemination and replication of DENV and ZIKV. Hence, our work reveals a dual role for hemocytes in Ae. aegypti mosquitoes, whereby phagocytosis is not required to control viral infection in the midgut but is essential to restrict systemic dissemination. Further understanding of the mechanism behind this duality could help the design of vector-based strategies to prevent transmission of arboviruses.
A conflicts’ classification for IoT-based services: a comparative survey

Recently, Internet of Things (IoT)-based systems, especially automation systems, have become an indispensable part of modern-day lives to support the controlling of the networked devices and providing context-aware and intelligent environments. IoT-based services/apps developed by the end-users interact with each other and share concurrent access to devices according to their preferences, which increases safety, security, and correctness issues in IoT systems. Due to the critical impacts resulting from these issues, IoT-based apps require a customized type of compilers or checking tools that capable of analyzing the structures of these apps and detecting different types of errors and conflicts either in intra-IoT app instructions or in inter-IoT apps interactions. A plethora of approaches and frameworks have been proposed to assist the best practices for end-users in developing their IoT-based apps and mitigate these errors and conflicts. This paper focuses on conflict classification and detection approaches in the context of IoT systems by investigating the current research techniques that provided conflicts’ classification or detection in IoT systems (published between 2014 and 2020). A classification of IoT-based apps interaction conflicts is proposed. The proposed conflicts’ classification provides a priori conflicts detection method based on the analysis of IoT app instructions’ relationships with utilizing the state-of-the-art Satisfiability Modulo Theories (SMT) model checking and formal notations. The current detection approaches are compared with each other according to the proposed conflicts’ classification to determine to which extend they cover different conflicts. Based on this comparison, we provide evidence that the existing approaches have a gap in covering different conflicts’ levels and types which yields to minimize the correctness and safety of IoT systems. We point out the need to develop a safety and security compiler or tool for IoT systems. Also, we recommend using a hybrid approach that combines model checking with a variety of languages and semantic technologies in developing future IoT-based apps verification frameworks to cover all levels and types of conflicts to guarantee and increase the safety, security, and correctness of IoT systems.
Molecular Characterization of Multidrug-Resistant Yersinia enterocolitica From Foodborne Outbreaks in Sweden

The foodborne pathogen Yersinia enterocolitica causes gastrointestinal infections worldwide. In the spring of 2019, the Swedish Public Health Agency and Statens Serum Institut in Denmark independently identified an outbreak caused by Yersinia enterocolitica 4/O:3 that after sequence comparison turned out to be a cross-border outbreak. A trace-back investigation suggested shipments of fresh prewashed spinach from Italy as a common source for the outbreak. Here, we determined the genome sequences of five Y. enterocolitica clinical isolates during the Swedish outbreak using a combination of Illumina HiSeq short-read and Nanopore Technologies’ MinION long-read whole-genome sequencing. WGS results showed that all clinical strains have a fully assembled chromosome of approximately 4.6 Mbp in size and a 72-kbp virulence plasmid; one of the strains was carrying an additional 5.7-kbp plasmid, pYE-tet. All strains showed a high pathogen probability score (87.5%) with associated genes for virulence, all of which are closely related to an earlier clinical strain Y11 from Germany. In addition, we identified a chromosomally encoded multidrug-resistance cassette carrying resistance genes against chloramphenicol (catA1), streptomycin (aadA1), sulfonamides (sul1), and a mercury resistance module. This chromosomally encoded Tn2670 transposon has previously been reported associated with IncFII plasmids in Enterobacteriaceae: a Shigella flexneri clinical isolate from Japan in 1950s, a Klebsiella pneumoniae outbreak from Australia in 1997, and Salmonella enterica serovar Typhimurium. Interestingly, we identified an additional 5.7-kbp plasmid with tetB (encoding an ABC transporter), Rep, and its own ORI and ORIt sites, sharing high homology with small tetB-Rep plasmids from Pasteurellaceae. This is the first time that Tn2670 and Pasteurellaceae plasmids have been reported in Y. enterocolitica. Taken together, our study showed that the Swedish Y. enterocolitica outbreak strains acquired multi-antibiotic and metal-resistance genes through horizontal gene transfer, suggesting a potential reservoir of intraspecies dissemination of multidrug-resistance genes among foodborne pathogens. This study also highlights the concern of food-chain contamination of prewashed vegetables as a perpetual hazard against public health.
Sex-Specific Temporal Trends in Overweight and Obese Among Schoolchildren From 2009 to 2018: An Age Period Cohort Analysis

Background: Our study examined the age, period, and cohort effects on overweight and obesity in children using a 10-year dataset collected from schoolchildren in Hualien, Taiwan. Methods: We used data from the annual health checkup of a total of 94,661 schoolchildren in primary schools and junior high schools in Hualien from 2009 to 2018. Children were defined as overweight or obese by the gender- and age-specific norm of the body mass index. We conducted the age-period-cohort (APC) analysis in boys and girls separately. Results: From 2009 to 2018, the rates of children overweight and obese were 12.78 and 14.23%, respectively. Boys had higher rates of overweight and obesity than girls (29.73 vs. 24.03%, P < 0.001). Based on APC analysis results, positive age effect existed regardless of gender. The risk of overweight or obesity of children aged 9 or 12 years was significantly higher compared to the average rate. As for period effect, a fluctuating downward trend in overweight was evident in 2016, and a similar trend in obesity was seen in 2017 across gender groups. The birth cohort of 2007 to 2009 had a significant higher proportion of overweight and obese than other birth cohorts. This indicated that the proportion of children overweight and obese in the young generation is higher than that in the old generation. Conclusion: An increased risk of children overweight or obese was associated with age and later birth cohort. For the period effect, the trend in the prevalence of overweight and obesity fluctuated downward slowly from 2016 to 2017.
Additional Value of PET/CT-Based Radiomics to Metabolic Parameters in Diagnosing Lynch Syndrome and Predicting PD1 Expression in Endometrial Carcinoma

Purpose We aim to compare the radiomic features and parameters on 2-deoxy-2-[fluorine-18] fluoro-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) between patients with endometrial cancer with Lynch syndrome and those with endometrial cancer without Lynch syndrome. We also hope to explore the biologic significance of selected radiomic features. Materials and Methods We conducted a retrospective cohort study, first using the 18F-FDG PET/CT images and clinical data from 100 patients with endometrial cancer to construct a training group (70 patients) and a test group (30 patients). The metabolic parameters and radiomic features of each tumor were compared between patients with and without Lynch syndrome. An independent cohort of 23 patients with solid tumors was used to evaluate the value of selected radiomic features in predicting the expression of the programmed cell death 1 (PD1), using 18F-FDG PET/CT images and RNA-seq genomic data. Results There was no statistically significant difference in the standardized uptake values on PET between patients with endometrial cancer with Lynch syndrome and those with endometrial cancer without Lynch syndrome. However, there were significant differences between the 2 groups in metabolic tumor volume and total lesion glycolysis (p < 0.005). There was a difference in the radiomic feature of gray level co-occurrence matrix entropy (GLCMEntropy; p < 0.001) between the groups: the area under the curve was 0.94 in the training group (sensitivity, 82.86%; specificity, 97.14%) and 0.893 in the test group (sensitivity, 80%; specificity, 93.33%). In the independent cohort of 23 patients, differences in GLCMEntropy were related to the expression of PD1 (rs =0.577; p < 0.001). Conclusions In patients with endometrial cancer, higher metabolic tumor volumes, total lesion glycolysis values, and GLCMEntropy values on 18F-FDG PET/CT could suggest a higher risk for Lynch syndrome. The radiomic feature of GLCMEntropy for tumors is a potential predictor of PD1 expression.