OBJECTIVES/GOALS: Hamsters develop COVID-19 similarly to people because the SARS-CoV-2 spike protein binds with high affinity to hamster ACE2 resulting in host cell entry and replication. Our goal was to establish a hamster model that mirrors the lung and brain pathophysiology observed in COVID-19. METHODS/STUDY POPULATION: Hamsters infected with SARS CoV-2 are sacrificed on day 1 and day 6 postinfection. Lung histopathology scoring model was implemented for assessment all pathological relevant changes in the lungs of infected animals on tissue sections stained with hematoxylin and eosin. To quantify the extent and severity of lung pathology, two scoring systems were used: the first evaluated all relevant changes in the lungs of the infected animals and the second evaluated only the pathology associated with the pulmonary vasculature. Percentage of airway affected, airway severity, bronchiolar epithelial hyperplasia, alveoli affected, alveolar severity, type II pneumocyte hyperplasia and vessels affected were analyzed. Total airway score plus total lung alveolar score give lung histopathology score. RESULTS/ANTICIPATED RESULTS: Compared to the control hamster, the hamsters day 1 postinfection, exhibited a higher total airway score [9.00 ± 1.35 vs. 0.25 ± 0.1; p DISCUSSION/SIGNIFICANCE: Establishing this outstanding small animal model of COVID-19 will facilitate studies investigating diagnostics, prognosis and response to treatment in COVID-19 disease. These studies will provide insights that will complement on-going clinical trials on angiotensin type 1 receptor (AT1R) blockers (ARBs) in COVID-19.

OBJECTIVES/GOALS: Rodents are the most widely used experimental animals to study disease mechanisms due to their availability and cost-effectiveness. An international drive to investigate the pathophysiology of COVID-19 is inhibited by the resistance of rats and mice to SARS-CoV-2 infection. Our goal was to establish an appropriate small animal model. METHODS/STUDY POPULATION: To recreate the cytokine storm that is associated with COVID-19, we injected angiotensin converting enzyme 2 knockout (ACE2KO) mice (C57BI/6 strain) with lipopolysaccharide (LPS) intraperitoneally and measured the expression of multiple cytokines as a function of time and LPS dose. We then chose a minimum dose (500ug/kg) and time (3h) when multiple cytokines were elevated to measure lung injury scores using a point-counting technique on tissue sections stained with hematoxylin and eosin. The data are expressed as mean percentage of grid points lying within the peribronchial and superficial area in up to 20 fields. Percentage of peribronchial and superficial intrapulmonary hemorrhage, congestion, neutrophil infiltration and area of alveolar space were all assessed. RESULTS/ANTICIPATED RESULTS: Compared to the wildtype group (WT-G), the LPS-injected ACE2KO mice (LPS-G) exhibited a higher percentage of peribronchial intrapulmonary hemorrhage [(%): LPS-G, 10.56 ± 2.06 vs. WT-G, 5.59 ± 0.53; p DISCUSSION/SIGNIFICANCE: Establishing this novel mouse model of COVID-19 will facilitate studies investigating tissue-specific mechanisms of pathogenesis in this disease. This model can also be used to discover novel therapeutic targets and the design of clinical trials focusing on diagnostics, treatments and outcomes in COVID-19.

According to the public data collected from the Health Commission of Gansu Province, China, regarding the COVID-19 pandemic during the summer epidemic cycle in 2022, the epidemiological analysis showed that the pandemic spread stability and the symptom rate (the number of confirmed cases divided by the sum of the number of asymptomatic cases and the number of confirmed cases) of COVID-19 were different among 3 main epidemic regions, Lanzhou, Linxia, and Gannan; both the symptom rate and the daily instantaneous symptom rate (daily number of confirmed cases divided by the sum of daily number of asymptomatic cases and daily number of confirmed cases) in Lanzhou were substantially higher than those in Linxia and Gannan. The difference in the food sources due to the high difference of the population ethnic composition in the 3 regions was probably the main driver for the difference of the symptom rates among the 3 regions. This work provides potential values for prevention and control of COVID-19 in different regions.

The current study aims to confirm the positive effects of dietary nano-Se on nutrients deposition and muscle fibre formation in grass carp fed with high-fat diet (HFD) before overwintering and to reveal its possible molecular mechanism. The lipid deposition, protein synthesis and muscle fibre formation in grass carp fed with regular diet (RD), HFD or HFD supplemented with nano-Se (0·3 or 0·6 mg/kg) for 60 d were tested. Results show that nano-Se significantly reduced lipid content, dripping loss and fibre diameter (P < 0·05), but increased protein content, post-mortem pH24 h and muscle fibre density (P < 0·05) in muscle of grass carp fed with HFD. Notably, dietary nano-Se decreased lipid deposition in the muscle by regulating amp-activated protein kinase activity and increased protein synthesis and fibre formation in muscle by activating target of rapamycin and myogenic determining factors pathways. In summary, dietary nano-Se can regulate the nutrients deposition and muscle fibre formation in grass carp fed with HFD, which exhibit potential benefit for improving flesh quality of grass carp fed with HFD.

This paper explores how factional competition shapes local media's coverage of negative political news. Employing news reports that appeared in Chinese national and local newspapers (2000–2014) coupled with data on the networks of elites, we find that local bureaucrats connected to strong national leaders tend to criticize members of weaker factions in politically damaging news reports. These adverse reports indeed harm the promotion prospects of the province leaders reported on in the articles, weakening the already weak factions and expanding the relative power of the strong factions. Our findings suggest that the loyalty-based competitive behaviors of political elites further tilt an already uneven playing field across political factions and facilitate power concentration in China.

Late Palaeozoic igneous rock associations in response to subduction, accretion, and final closure of the eastern Palaeo-Asian Ocean play a significant role in understanding the geodynamic evolution of the southeastern Central Asian Orogenic Belt. Previous studies have identified a Permian arc magmatic belt associated with the southward-dipping subduction of the eastern Palaeo-Asian Ocean along the Solonker–Changchun suture zone. The genetic mechanism and associated geodynamic settings are of great importance in deciphering the evolution of the eastern Palaeo-Asian Ocean. This paper presents zircon U–Pb–Hf isotope and whole-rock geochemical analyses for a suite of magmatic rocks including the early Permian diorite porphyrites (ca. 281.0 Ma), andesites (ca. 276 Ma) and rhyolites (ca. 275 Ma) in the Kulun region. The diorite porphyrites and andesites have high SiO2 and total alkali contents, and low MgO contents and Mg no. values, with enrichments in large ion lithophile elements and depletions in high-field-strength elements. These geochemical characteristics, together with low-Sr and high-Yb contents, a weak concave-upward shape of middle rare earth elements and negative Eu anomalies, suggest that these intermediate igneous rocks were generated by partial melting of amphibolitic lower crust at a crustal depth of 30–40 km. The rhyolites have heterogeneous isotopic compositions, with ϵHf(t) values and TDM2 ages of –20.8 to +0.5 and 3578∼1494 Ma, implying that they were likely derived from partial melting of a mixed source dominated by recycled ancient crust with minor juvenile crustal materials. The rhyolites show potassic affinity with relatively high K2O and very low Na2O, which was attributed to liquid immiscibility of felsic magma and subsequent limited fractional crystallization of plagioclase. The regional igneous associations, metamorphic events, and coeval sedimentary rocks along the Solonker–Changchun suture zone indicate that the early Permian igneous rocks were formed in an active continental arc environment in response to southward subduction of the eastern Palaeo-Asian Ocean.

Background: Although small- and medium-sized hospitals comprise most healthcare providers in South Korea, data on antibiotic usage is limited in these facilities. We evaluated the pattern of antibiotic usage and its appropriateness in hospitals with <400 beds in South Korea. Methods: A multicenter retrospective study was conducted in 10 hospitals (6 long-term care hospitals, 3 acute-care hospitals, and 1 orthopedic hospital), with <400 beds in South Korea. We analyzed patterns of antibiotic prescription and their appropriateness in the participating hospitals. Data on the monthly antibiotic prescriptions and patient days for hospitalized patients were collected using electronic databases from each hospital. To avoid the effect of the COVID-19 pandemic, data were collected from January to December 2019. For the evaluation of the appropriateness of the prescription, 25 patients under antibiotic therapy were randomly selected at each hospital over 2 separate periods. Due to the heterogeneity of their characteristics, the orthopedics hospital was excluded from the analysis. The collected data were reviewed, and the appropriateness of antibiotic prescriptions was evaluated by 5 specialists in infectious diseases (adult and pediatric). Data from 2 hospitals were assigned to each specialist. The appropriateness of antibiotic prescriptions was evaluated from 3 aspects: route of administration, dose, and class. If the 3 aspects were ‘optimal,’ the prescription was considered ‘optimal.’ If only the route was ‘optimal,’ and the dose and/or class was ‘suboptimal,’ but not ‘inappropriate,’ it was considered ‘suboptimal.’ If even 1 aspect was ‘inappropriate,’ it was classified as ‘inappropriate.’ Results: The most commonly prescribed antibiotics in long-term care hospitals was fluoroquinolone, followed by β-lactam/β-lactamase inhibitor (antipseudomonal). In acute-care hospitals, these were third-generation cephalosporin, followed by first-generation cephalosporin and second-generation cephalosporin. The major antibiotics that were prescribed in the orthopedics hospital was first-generation cephalosporin. Only 2.3% of the antibiotics were administered inappropriately. In comparison, 15.3% of patients were prescribed an inappropriate dose. The proportion of inappropriate antibiotic prescriptions was 30.6% of the total antibiotic prescriptions. Conclusions: The antibiotic usage patterns vary between small- and medium-sized hospitals in South Korea. The proportion of inappropriate prescriptions exceeded 30% of the total antibiotic prescriptions.

Funding: None

Disclosures: None

OBJECTIVES/GOALS: The SARS-CoV-2 (Severe Acute Respiratory Syndrome CoronaVirus-2), which underlies the current COVID-19 pandemic, among other tissues, also targets the central nervous system (CNS). The goal of this study is to investigate mechanisms of neuroinflammation in Lipopolysaccharides (LPS)-treated mouse model and SARS-CoV-2-infected hamsters. METHODS/STUDY POPULATION: In this research I will assay vascular reactivity of cerebral vessels to assess vascular dysfunction within the microcirculation. I will determine expression of proinflammatory cytokines, coagulation factors and AT1 receptors (AT1R) in isolated microvessels from the circle of Willis to assess inflammation, thrombosis and RAS activity in the microvasculature. LPS and SARS-CoV-2, are both associated with coagulopathies and because of that I will measure concentration of PAI-1, von Willebrand Factor, thrombin and D-dimer to assess the thrombotic pathway in the circulation. Histology and immunohistochemistry will assess immune cell type infiltration into the brain parenchyma, microglia activation and severity of neuroinflammation and neural injury. RESULTS/ANTICIPATED RESULTS: We hypothesize that under conditions of reduced ACE2 (e.g., SARS-CoV-2 infection), AT1R activity is upregulated in the microvasculature. In the presence of an inflammatory insult, these AT1Rs promote endothelialitis and immunothrombosis through pro-thrombotic pathways and pro-inflammatory cytokine production leading to endothelial dysfunction in the microvasculature, blood brain barrier (BBB) injury, deficits in cognition and increased anxiety. We will test this hypothesis through 2 aims: Aim 1: Determine the role of the pro-injury arm of the RAS in the pathophysiology of the brain in animal models of neuroinflammation and COVID-19. Aim 1: Determine the role of the protective arm of the RAS in the pathophysiology of the brain in animal models of neuroinflammation and COVID-19. DISCUSSION/SIGNIFICANCE: This study will provide insights that will complement on-going clinical trials on angiotensin type 1 receptor (AT1R) blockers (ARBs) in COVID-19. This research is a necessary first step in understanding mechanisms of brain pathogenesis that can set the groundwork for future studies of more complex models of disease.

This article examines how violence against citizens affects their political attitudes and behavior in the long run, and how those effects vary over time. We construct and analyze a novel dataset on the victims of Taiwan's February 28 Incident, in 1947, with survey data spanning 1990 to 2017. Our empirical analysis shows that cohorts having directly or indirectly experienced the Incident are less likely to support the Kuomintang Party (KMT), the former authoritarian ruling party responsible for the Incident. They tend to disagree with the key conventional policy stand of the KMT (unification with mainland China), are more likely to self-identify as Taiwanese, and are less likely to vote for KMT presidential candidates. Taiwan's residents who were born in towns with larger number of casualties during the Incident are more likely to reject unification. Finally, the effects are found to vary over the period following democratization.

Late Mesozoic igneous rocks are important for deciphering the Mesozoic tectonic setting of NE China. In this paper, we present whole-rock geochemical data, zircon U–Pb ages and Lu–Hf isotope data for Early Cretaceous volcanic rocks from the Tulihe area of the northern Great Xing’an Range (GXR), with the aim of evaluating the petrogenesis and genetic relationships of these rocks, inferring crust–mantle interactions and better constraining extension-related geodynamic processes in the GXR. Zircon U–Pb ages indicate that the rhyolites and trachytic volcanic rocks formed during late Early Cretaceous time (c. 130–126 Ma). Geochemically, the highly fractionated I-type rhyolites exhibit high-K calc-alkaline, metaluminous to weakly peraluminous characteristics. They are enriched in light rare earth elements (LREEs) and large-ion lithophile elements (LILEs) but depleted in high-field-strength elements (HFSEs), with their magmatic zircons ϵHf(t) values ranging from +4.1 to +9.0. These features suggest that the rhyolites were derived from the partial melting of a dominantly juvenile, K-rich basaltic lower crust. The trachytic volcanic rocks are high-K calc-alkaline series and exhibit metaluminous characteristics. They have a wide range of zircon ϵHf(t) values (−17.8 to +12.9), indicating that these trachytic volcanic rocks originated from a dominantly lithospheric-mantle source with the involvement of asthenospheric mantle materials, and subsequently underwent extensive assimilation and fractional crystallization processes. Combining our results and the spatiotemporal migration of the late Early Cretaceous magmatic events, we propose that intense Early Cretaceous crust–mantle interaction took place within the northern GXR, and possibly the whole of NE China, and that it was related to the upwelling of asthenospheric mantle induced by rollback of the Palaeo-Pacific flat-subducting slab.

To understand the characteristics and influencing factors related to cluster infections in Jiangsu Province, China, we investigated case reports to explore transmission dynamics and influencing factors of scales of cluster infection. The effectiveness of interventions was assessed by changes in the time-dependent reproductive number (Rt). From 25th January to 29th February, Jiangsu Province reported a total of 134 clusters involving 617 cases. Household clusters accounted for 79.85% of the total. The time interval from onset to report of index cases was 8 days, which was longer than that of secondary cases (4 days) (χ2 = 22.763, P < 0.001) and had a relationship with the number of secondary cases (the correlation coefficient (r) = 0.193, P = 0.040). The average interval from onset to report was different between family cluster cases (4 days) and community cluster cases (7 days) (χ2 = 28.072, P < 0.001). The average time interval from onset to isolation of patients with secondary infection (5 days) was longer than that of patients without secondary infection (3 days) (F = 9.761, P = 0.002). Asymptomatic patients and non-familial clusters had impacts on the size of the clusters. The average reduction in the Rt value in family clusters (26.00%, 0.26 ± 0.22) was lower than that in other clusters (37.00%, 0.37 ± 0.26) (F = 4.400, P = 0.039). Early detection of asymptomatic patients and early reports of non-family clusters can effectively weaken cluster infections.

Potential secondary influences on titanium distribution should be evaluated when using ash beds as volcanic source indicators and for correlation purposes. In this study, well-correlated altered ash beds in Permian–Triassic boundary (PTB) successions of various facies in South China were investigated to better understand their use in source discrimination and stratigraphic correlation. The ash beds deposited in lacustrine and paludal facies contain significantly more Ti relative to deposits in marine facies. Neoformed anatase grains nanometres to micrometres in size are associated closely with clay minerals, whereas detrital anatase was observed in the remnants of altered ash beds of terrestrial facies. Extraction of the clay fraction of altered ash beds may exclude significantly detrital accessory minerals such as anatase and rutile added during sediment reworking, and the concentrations of immobile elements in the clay fraction may therefore be used to interpret more effectively their source igneous rocks.

A study was conducted to identify whether composted manure and straw amendments (replacement of a portion of chemical fertilizer [50% of the total nitrogen application] with composted pig manure, and straw return [all straw from the previous rice crop] combined with chemical fertilizer) compared with no fertilization and chemical fertilizer only would change the dominant species of wheat-associated weeds as well as influence their growth and seed yield in a rice (Oryza sativa L.)–wheat (Triticum aestivum L.) rotation system. The study was initiated in 2010, and the treatment effects on the species, density, plant height, shoot biomass, seed yield of dominant weeds, and wheat yields were assessed in 2017 and 2018. Fertilization significantly increased the height, density, and yield of wheat, as well as the shoot biomass of wheat-associated weeds, but decreased the weed species number. A total of 17 and 14 weed species were recorded in the experimental wheat fields in 2017 and 2018, respectively. The most dominant weed species were American sloughgrass [Beckmannia syzigachne (Steud.) Fernald] and catchweed bedstraw (Galium aparine L.), which made up more than 64% of the weed community in all treatments. When the chemical fertilizer application was amended with pig manure compost and straw return, the relative abundance of B. syzigachne significantly decreased, while the relative abundance of G. aparine significantly increased. The application of the chemical fertilizer-only treatment resulted in increases in the density, shoot biomass, and seed yield of B. syzigachne, while the composted manure and straw amendments applied together with chemical fertilizer led to significant increases in the density, shoot biomass, and seed yield of G. aparine. Consequently, further research on ways to promote greater cropping system diversity will be needed to prevent the selection of weed species that are adapted to a limited suite of crop management practices.