Does COVID-19 Affect Farmland Prices? How and Why?

COVID-19 has profoundly impacted the global economy, particularly the agricultural sector. However, relatively little attention has been paid to the relationship between COVID-19 and the farmland market. A few descriptive studies have speculated about the impact of COVID-19 on farmland prices but presented no quantitative evidence. This study provides quantitative evidence on the causal effect of COVID-19 on farmland prices using the difference-in-differences method with population-based data on farmland transactions in Taiwan. While prior descriptive studies argued that increased farmland prices associated with COVID-19 were largely driven by macroeconomic conditions, we found that the onset of COVID-19 increased farmland prices by 5.1%, even after controlling for macroeconomic conditions and parcel-level farmland characteristics. Furthermore, we found that government payments are likely responsible for these increases in farmland prices. Financial assistance easing the economic burdens of the agricultural sector can also stabilize farmland prices.

A review on quality control, toxicity and clinical application of Amomum tsao-ko Crevost & Lemarié

The dried fruit of Amomum tsao-ko Crevost & Lemarié, a perennial herb of Cardamom in Zingiberaceae, has been widely used in food and as a folk medicine. It is used not only as an important food additive and spice for removing peculiar smell and improving taste, but also as a traditional Chinese medicine with significant efficacy in treating many kinds of disorders. Based on the high edible and medicinal value, large amounts of investigation have been reported for A. tsaoko in the past several years. This review specifically summarises its quality control, toxicology and clinical application, about which no literature had systematically reviewed, based on our best acknowledge. The current quality control of A. tsaoko is based on the content of volatile oil, which should be no less than 1.4% according to the Pharmacopoeia of the People's Republic of China (2020 edition), while a more possible Q-Markers should be developed to focus on either a specific bioactive ingredient or a component correlated with a certain clinical efficacy. Toxicity research suggests that A. tsaoko actually belongs to the non-toxic substance, although citral and 1,8-cineole, two main components of A. tsaoko, is hepatotoxic for the former and displays low acute toxicity and sub-chronic oral toxicity for the latter, but no obviously accumulative toxicity has so far been discovered for A. tsaoko. In clinical practice, A. tsaoko is often used in treatment of dampness/cold resistance, malaria, vomiting, fullness and epigastric distension across additional disorders, such as SARS, COVID-19 and hepatitis.

Construction and Application of in vitro Alveolar Models Based on 3D Printing Technology

Increasing lung diseases, mutating coronaviruses, and the development of new compounds urgently require biomimetic in vitro lung models for lung pathology, toxicology, and pharmacology. The current construction strategies for lung models mainly include animal models, 2D cell culture, lung-on-a-chip, and lung organoids. However, current models face difficulties in reproducing in vivo-like alveolar size and vesicle-like structures, and are unable to contain multiple cell types. In this study, a strategy for constructing alveolar models based on degradable hydrogel microspheres is proposed. Hydrogel microspheres, 200–250 μm in diameter, were prepared using a self-developed printing technique driven by alternating viscous and inertial forces. Microcapsules were further constructed using a coacervation-based layer-by-layer technique and core liquefaction. Three types of cells were inoculated and co-cultured on hydrogel capsules based on optimized microcapsule surface treatment strategies. Finally, an in vitro three-dimensional endothelial alveolar model with a multicellular composition and vesicle-like structure with a diameter of approximately 230 μm was successfully constructed. Cells in the constructed alveolar model maintained a high survival rate. The LD50 values of glutaraldehyde based on the constructed models were in good agreement with the reference values, validating the potential of the model for future toxicant and drug detection.

What Do You Get from Turning on Your Video? Effects of Videoconferencing Affordances on Remote Class Experience During COVID-19 (preprint)

The outbreak of COVID-19 forced schools to swiftly transition from in-person classes to online or remote offerings, making educators and learners alike rely on online videoconferencing platforms. Platforms like Zoom offer audio-visual channels of communication and include features that are designed to approximate the classroom experience. However, it is not clear how students' learning experiences are affected by affordances of the videoconferencing platforms or what underlying factors explain the differential effects of these affordances on class experiences of engagement, interaction, and satisfaction. In order to find out, we conducted two online survey studies: Study 1 (N = 176) investigated the effects of three types of videoconferencing affordances (i.e., modality, interactivity, and agency affordances) on class experience during the first two months after the transition to online learning. Results showed that usage of the three kinds of affordances was positively correlated with students' class engagement, interaction, and satisfaction. Perceived anonymity, nonverbal cues, and comfort level were found to be the key mediators. In addition, students' usage of video cameras in class was influenced by their classmates. Study 2 (N = 256) tested the proposed relationships at a later stage of the pandemic and found similar results, thus serving as a constructive replication. This paper focuses on reporting the results of Study 1 since it captures the timely reactions from students when they first went online, and the second study plays a supplementary role in verifying Study 1 and thereby extending its external validity. Together, the two studies provide insights for instructors on how to leverage different videoconferencing affordances to enhance the virtual learning experience. Design implications for digital tools in online education are also discussed.

Caution of retinal toxicity using chloroquine and hydroxychloroquine in the treatment of COVID-19

"Chloroquine phosphate" was listed as a trial drug in diagnosis and treatment program of COVID-19 (trial sixth edition), and the application of chloroquine and hydroxychloroquine treatment for COVID-19 in medical institutions also increased. Chloroquine and hydroxychloroquine have certain retinal toxicity, its mechanism is still unclear, due to different drug tolerance, the risk degree of retinal toxicity in COVID-19 treatment is unclear. Therefore, when using chloroquine and hydroxychloroquine in the treatment of COVID-19, it is recommended to choose the appropriate dosage according to patients' situation, and adopt necessary ophthalmic screening for patients with high risk to prevent the occurrence of retinopathy. In this paper, we described the risk factors, clinical manifestations and screening methods of retinal toxicity caused by chloroquine and hydroxychloroquine, in order to provide references for the safer use of chloroquine and hydroxychloroquine in the treatment of COVID-19.

Psychological morbidities and fatigue in patients with confirmed COVID-19 during disease outbreak: prevalence and associated biopsychosocial risk factors (preprint)

Objective: The coronavirus disease 2019 (COVID-19) - a novel and highly infectious pneumonia - has now spread across China and beyond for over four months. However, its psychological impact on patients is unclear. We aim to examine the prevalence and associated risk factors for psychological morbidities and fatigue in patients with confirmed COVID-19 infection. Methods: Amidst the disease outbreak, 41 out of 105 COVID-19 patients in a local designated hospital in China were successfully assessed using a constellation of psychometric questionnaires to determine their psychological morbidities and fatigue. Several potential biopsychosocial risk factors (including pre-existing disabilities, CT severity score of pneumonia, social support, coping strategies) were assessed through multivariable logistic regression analyses to clarify their association with mental health in patients. Results: 43.9% of 41 patients presented with impaired general mental health, 12.2% had post-traumatic stress disorder (PTSD) symptoms, 26.8% had anxiety and/or depression symptoms, and 53.6% had fatigue. We did not find any association between pneumonia severity and psychological morbidities or fatigue in COVID-19 patients. However, high perceived stigmatization was associated with an increased risk of impaired general mental health and high perceived social support was associated with decreased risk. Besides, negative coping inclination was associated with an increased risk of PTSD symptoms; high perceived social support was associated with a decreased risk of anxiety and/or depression symptoms. Conclusions: Psychological morbidities and chronic fatigue are common among COVID-19 patients. Negative coping inclination and being stigmatized are primary risk factors while perceived social support is the main protective factor.

Broad-spectrum antivirals of protoporphyrins inhibit the entry of highly pathogenic emerging viruses (preprint)

Severe emerging and re-emerging viral infections such as Lassa fever, Avian influenza (AI), and COVID-19 caused by SARS-CoV-2 urgently call for new strategies for the development of broad-spectrum antivirals targeting conserved components in the virus life cycle. Viral lipids are essential components, and viral-cell membrane fusion is the required entry step for most unrelated enveloped viruses. In this paper, we identified a porphyrin derivative of protoporphyrin IX ( PPIX ) that showed broad antiviral activities in vitro against a panel of enveloped pathogenic viruses including Lassa virus (LASV), Machupo virus (MACV), and SARS-CoV-2 as well as various subtypes of influenza A viral strains with IC 50 values ranging from 0.91±0.25 μM to 1.88±0.34 μM. A mechanistic study using influenza A/Puerto Rico/8/34 (H1N1) as a testing strain showed that PPIX inhibits the infection in the early stage of virus entry through biophysically interacting with the hydrophobic lipids of enveloped virions, thereby inhibiting the formation of the negative curvature required for fusion and blocking the entry of enveloped viruses into host cells. In addition, the preliminary antiviral activities of PPIX were further assessed by testing mice infected with the influenza A/Puerto Rico/8/34 (H1N1) virus. The results showed that compared with the control group without drug treatment, the survival rate and mean survival time of the mice treated with PPIX were apparently prolonged. These data encourage us to conduct further investigations using PPIX as a lead compound for the rational design of lipid-targeting antivirals for the treatment of infection with enveloped viruses.

Calcium channel blocker amlodipine besylate is associated with reduced case fatality rate of COVID-19 patients with hypertension (preprint)

The coronavirus disease (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now spread to more than 100 countries posing as a serious threat to the public health on a global scale. Patients with comorbidity such as hypertension suffer more severe infection with elevated case fatality rate. Development of effective anti-viral drug is in urgent need to treat COVID-19 patients. Here we report that calcium channel blockers (CCBs), a type of anti-hypertension drugs that are widely used in the clinics, can significantly inhibit the post-entry replication events of SARS-CoV-2 in vitro. Comparison with two other major types of anti-hypertension drugs, the angiotensin converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB), showed that only CCBs display significant anti-SARS-CoV-2 efficacy. Combined treatment with chloroquine and CCBs significantly enhanced the anti-SARS-CoV-2 efficacy. Retrospective clinical investigation of COVID-19 patients revealed that the CCB amlodipine besylate administration was associated with reduced case fatality rate of patients with hypertension. Results from this study suggest that CCB administration for COVID-19 patients with hypertension as the comorbidity might improve the disease outcome.

Immunoglobulin fragment F(ab')2 against RBD potently neutralizes SARS-CoV-2 in vitro (preprint)

COVID-19 caused by the emerging human coronavirus, SARS-CoV-2, has become a global pandemic, leading a serious threat to human health. So far, there is none vaccines or specific antiviral drugs approved for that. Therapeutic antibodies for SARS-CoV-2, was obtained from hyper immune equine plasma in this study. Herein, SARS-CoV-2 RBD with gram level were obtained through Chinese hamster ovary cells high-density fermentation. The binding of RBD to SARS-CoV-2 receptor, human ACE2, was verified and the efficacy of RBD in vivo was tested on mice and then on horses. As a result, RBD triggered high-titer neutralizing antibodies in vivo, and immunoglobulin fragment F(ab)2 was prepared from horse antisera through removing Fc. Neutralization test demonstrated that RBD-specific F(ab)2 inhibited SARS-CoV-2 with EC50 at 0.07 g/ml, showing a potent inhibitory effect on SARS-CoV-2. These results highlights as RBD-specific F(ab)2 as therapeutic candidate for SARS-CoV-2.

Structural basis for the inhibition of COVID-19 virus main protease by carmofur, an antineoplastic drug (preprint)

The antineoplastic drug Carmofur was shown to inhibit SARS-CoV-2 main protease (Mpro). Here the X-ray crystal structure of Mpro in complex with Carmofur reveals that the carbonyl reactive group of Carmofur is covalently bound to catalytic Cys145, whereas its fatty acid tail occupies the hydrophobic S2 subsite. Carmofur inhibits viral replication in cells (EC50 = 24.30 M) and it is a promising lead compound to develop new antiviral treatment for COVID-19.

Novel and potent inhibitors targeting DHODH, a rate-limiting enzyme in de novo pyrimidine biosynthesis, are broad-spectrum antiviral against RNA viruses including newly emerged coronavirus SARS-CoV-2 (preprint)

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of coronavirus SARS-CoV-2. Existing direct-acting antiviral (DAA) drugs cannot be applied immediately to new viruses because of virus-specificity, and the development of new DAA drugs from the beginning is not timely for outbreaks. Thus, host-targeting antiviral (HTA) drugs have many advantages to fight against a broad spectrum of viruses, by blocking the viral replication and overcoming the potential viral mutagenesis simultaneously. Herein, we identified two potent inhibitors of DHODH, S312 and S416, with favorable drug-like and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus (H1N1, H3N2, H9N2), Zika virus, Ebola virus, and particularly against the recent novel coronavirus SARS-CoV-2. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knocking-out cells. We also proposed the drug combination of DAA and HTA was a promising strategy for anti-virus treatment and proved that S312 showed more advantageous than Oseltamivir to treat advanced influenza diseases in severely infected animals. Notably, S416 is reported to be the most potent inhibitor with an EC50 of 17nM and SI value >5882 in SARS-CoV-2-infected cells so far. This work demonstrates that both our self-designed candidates and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-repression may have clinical potentials not only to influenza but also to COVID-19 circulating worldwide, no matter such viruses mutate or not.