Miracle-dz/UniFAR-FTUs huggingface dataset:
Broad Anti-coronavirus Activity of Food and Drug Administration-Approved Drugs against SARS-CoV-2 In Vitro and SARS-CoV In Vivo

There are no FDA-approved antivirals for any coronavirus, including SARS-CoV-2. Numerous drugs are already approved for human use that may have antiviral activity and therefore could potentially be rapidly repurposed as antivirals. Here, we present data assessing the antiviral activity of 20 FDA-approved drugs against SARS-CoV-2 that also inhibit SARS-CoV and MERS-CoV in vitro. We found that 17 of these inhibit SARS-CoV-2, suggesting that they may have pan-anti-coronaviral activity. We directly followed up seven of these and found that they all inhibit infectious-SARS-CoV-2 production. Moreover, we evaluated chloroquine and chlorpromazine in vivo using mouse-adapted SARS-CoV. We found that neither drug inhibited viral replication in the lungs, but both protected against clinical disease. ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China at the end of 2019 and has rapidly caused a pandemic, with over 20 million recorded COVID-19 cases in August 2020 (https://covid19.who.int/). There are no FDA-approved antivirals or vaccines for any coronavirus, including SARS-CoV-2. Current treatments for COVID-19 are limited to supportive therapies and off-label use of FDA-approved drugs. Rapid development and human testing of potential antivirals is urgently needed. Numerous drugs are already approved for human use, and subsequently, there is a good understanding of their safety profiles and potential side effects, making them easier to fast-track to clinical studies in COVID-19 patients. Here, we present data on the antiviral activity of 20 FDA-approved drugs against SARS-CoV-2 that also inhibit SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). We found that 17 of these inhibit SARS-CoV-2 at non-cytotoxic concentrations. We directly followed up seven of these to demonstrate that all are capable of inhibiting infectious SARS-CoV-2 production. Moreover, we evaluated two of these, chloroquine and chlorpromazine, in vivo using a mouse-adapted SARS-CoV model and found that both drugs protect mice from clinical disease. IMPORTANCE There are no FDA-approved antivirals for any coronavirus, including SARS-CoV-2. Numerous drugs are already approved for human use that may have antiviral activity and therefore could potentially be rapidly repurposed as antivirals. Here, we present data assessing the antiviral activity of 20 FDA-approved drugs against SARS-CoV-2 that also inhibit SARS-CoV and MERS-CoV in vitro. We found that 17 of these inhibit SARS-CoV-2, suggesting that they may have pan-anti-coronaviral activity. We directly followed up seven of these and found that they all inhibit infectious-SARS-CoV-2 production. Moreover, we evaluated chloroquine and chlorpromazine in vivo using mouse-adapted SARS-CoV. We found that neither drug inhibited viral replication in the lungs, but both protected against clinical disease.
Effects of dietary glycerol inclusion on growth performance, carcass and meat quality characteristics, glycogen content, and meat volatile compounds in Korean cattle steers

Objective We have tested our hypothesis that inclusion of purified glycerol as a replacer of portions of dried distillers grain with solubles (DDGS) would affect growth performance, rumen fermentation and blood parameters, carcass and sensory traits, reducing sugar and glycogen contents, and volatile compound profiles in longissimus thoracis (LT) in Korean cattle steers. Methods A total of 20 Korean cattle steers (27.0±0.2 months old; 647±10.5 kg body weight [BW]) were assigned to a conventional control group or a glycerol group (3.17% purified glycerol addition as a replacement for DDGS and molasses). The steers were individually allowed to receive the experimental concentrate at the daily amount of 1.5% of their individual BW and a total 1.0 of kg/d of rice straw twice daily. The feeding trial was conducted for a period of 20 weeks. Results Glycerol supplementation (GS) increased (p = 0.001) concentrate intake. However, GS did not affect (p>0.05) average daily gain, feed efficiency, and ruminal volatile fatty acid concentrations. GS tended to increase (p≤0.10) serum glucose concentrations at the 16th and 20th weeks. GS decreased (p = 0.001) LT pH. GS did not affect (p>0.05) carcass traits and the chemical or physicochemical compositions, reducing sugar or glycogen contents, sensory traits, and most of volatile compounds in the LT. Conclusion The inclusion of purified glycerol as a replacement for DDGS in the finishing diet did not affect growth performance, rumen fermentation parameters, and carcass quality in Korean cattle. The purified glycerol could be used as a substitute for other energy sources such as DDGS in beef cattle, depending on the price.
Ca2+‐dependent release of ATP from astrocytes affects herpes simplex virus type 1 infection of neurons

Astrocytes provide metabolic support for neurons and modulate their functions by releasing a plethora of neuroactive molecules diffusing to neighboring cells. Here we report that astrocytes also play a role in cortical neurons' vulnerability to Herpes simplex virus type‐1 (HSV‐1) infection through the release of extracellular ATP. We found that the interaction of HSV‐1 with heparan sulfate proteoglycans expressed on the plasma membrane of astrocytes triggered phospholipase C‐mediated IP3‐dependent intracellular Ca2+ transients causing extracellular release of ATP. ATP binds membrane purinergic P2 receptors (P2Rs) of both neurons and astrocytes causing an increase in intracellular Ca2+ concentration that activates the Glycogen Synthase Kinase (GSK)‐3β, whose action is necessary for HSV‐1 entry/replication in these cells. Indeed, in co‐cultures of neurons and astrocytes HSV‐1‐infected neurons were only found in proximity of infected astrocytes releasing ATP, whereas in the presence of fluorocitrate, an inhibitor of astrocyte metabolism, switching‐off the HSV‐1‐induced ATP release, very few neurons were infected. The addition of exogenous ATP, mimicking that released by astrocytes after HSV‐1 challenge, restored the ability of HSV‐1 to infect neurons co‐cultured with metabolically‐inhibited astrocytes. The ATP‐activated, P2R‐mediated, and GSK‐3‐dependent molecular pathway underlying HSV‐1 infection is likely shared by neurons and astrocytes, given that the blockade of either P2Rs or GSK‐3 activation inhibited infection of both cell types. These results add a new layer of information to our understanding of the critical role played by astrocytes in regulating neuronal functions and their response to noxious stimuli including microbial agents via Ca2+‐dependent release of neuroactive molecules.
A retrospective study on nested PCR detection of syphilis treponemes in clinical samples: PCR detection contributes to the diagnosis of syphilis in patients with seronegative and serodiscrepant results

Syphilis, caused by Treponema pallidum ssp. pallidum (TPA), is a persisting global health problem. Although syphilis diagnostics relies mainly on serology, serological tests have some limitations, and it is recommended that the final diagnosis be supported by additional tests. The purpose of this study was to analyze the relationship between serology and PCR in syphilis diagnostics. From the year 2004 to May 2019, a total of 941 samples were taken from 833 patients suspected of having syphilis, in Czech Republic. In all these samples, both nested PCR detection of TPA and serology testing were performed. Of the 941 samples, 126 were seronegative, 651 were seropositive, and 164 were serodiscrepant. Among seronegative samples (n = 126), 11 were PCR-positive (8.7%). Among seropositive samples (n = 651; i.e., samples positive for both non-treponemal and treponemal serology tests), 368 samples were PCR-positive (56.5%). The remaining 164 serodiscrepant samples included RPR negative and treponemal serological test-positive samples (n = 154) and a set of 10 RPR-positive samples negative in treponemal serological tests. While the first group revealed 73 PCR-positive samples (47.4%), the second revealed 5 PCR positive samples (50.0%). PCR detection rates were highest in primary syphilis, with lower rates in the secondary and undetermined syphilis stages. As shown here, the nested PCR can improve diagnostics of syphilis, especially in seronegative patients and in patients with discrepant serology.
Racial and Ethnic Disparities in Patient Experiences in the United States: 4-Year Content Analysis of Twitter

Background Racial and ethnic minority groups often face worse patient experiences compared with the general population, which is directly related to poorer health outcomes within these minority populations. Evaluation of patient experience among racial and ethnic minority groups has been difficult due to lack of representation in traditional health care surveys. Objective This study aims to assess the feasibility of Twitter for identifying racial and ethnic disparities in patient experience across the United States from 2013 to 2016. Methods In total, 851,973 patient experience tweets with geographic location information from the United States were collected from 2013 to 2016. Patient experience tweets included discussions related to care received in a hospital, urgent care, or any other health institution. Ordinary least squares multiple regression was used to model patient experience sentiment and racial and ethnic groups over the 2013 to 2016 period and in relation to the implementation of the Patient Protection and Affordable Care Act (ACA) in 2014. Results Racial and ethnic distribution of users on Twitter was highly correlated with population estimates from the United States Census Bureau’s 5-year survey from 2016 (r2=0.99; P<.001). From 2013 to 2016, the average patient experience sentiment was highest for White patients, followed by Asian/Pacific Islander, Hispanic/Latino, and American Indian/Alaska Native patients. A reduction in negative patient experience sentiment on Twitter for all racial and ethnic groups was seen from 2013 to 2016. Twitter users who identified as Hispanic/Latino showed the greatest improvement in patient experience, with a 1.5 times greater increase (P<.001) than Twitter users who identified as White. Twitter users who identified as Black had the highest increase in patient experience postimplementation of the ACA (2014-2016) compared with preimplementation of the ACA (2013), and this change was 2.2 times (P<.001) greater than Twitter users who identified as White. Conclusions The ACA mandated the implementation of the measurement of patient experience of care delivery. Considering that quality assessment of care is required, Twitter may offer the ability to monitor patient experiences across diverse racial and ethnic groups and inform the evaluation of health policies like the ACA.
Quantification of High Temperature Transition Al2O3 and Their Phase Transformations.

High temperature treatment of γ-Al 2 O 3 can lead to a series of polymorphic transformations, including the formation of δ-Al 2 O 3 and θ-Al 2 O 3 . Quantification of the microstructure in the range where δ- and θ-Al 2 O 3 are formed represents a formidable challenge as both phases accommodate a high degree of structural disorder. In this work, we explore the use of an XRD recursive stacking formalism for quantification of high temperature transition aluminas. We formulate the recursive stacking methodology for modelling of disorder in δ-Al 2 O 3 and twinning in θ-Al 2 O 3 and show that explicitly accounting for the disorder is necessary to reliably model the XRD patterns of high temperature transition alumina. In addition, we use the recursive stacking approach to study phase transformation during high temperature (1050 ºC) treatment. We show that the two different intergrowth modes of δ-Al 2 O 3 have different transformation characteristics, and that a significant portion of δ-Al 2 O 3 is stabilized with θ-Al 2 O 3 even after prolonged high-temperature exposures. In discussions, we outline the limitation of the current XRD approach and discuss a possible multimodal XRD and NMR approach which can improve analysis of complex transition aluminas.
Prkar1a haploinsufficiency ameliorates the growth hormone excess phenotype in Aip-deficient mice.

BACKGROUND Mutations of the regulatory subunit (PRKAR1A) of the cAMP-dependent protein kinase (PKA), leading to activation of the PKA pathway, are the genetic cause of Carney complex which is frequently accompanied by somatotroph tumors. Aryl hydrocarbon receptor-interacting protein (AIP) mutations lead to somatotroph tumorigenesis in mice and humans. The mechanisms of AIP-dependent pituitary tumorigenesis are still under investigation and evidence points to a connection between the AIP and PKA pathways. In this study, we explore the combined effects of Aip and Prkar1a deficiency on mouse phenotype and, specifically, pituitary histopathology. METHODS Aip +/- mice were compared to double heterozygous Aip+/-, Prkar1a+/- mice. The phenotype (including histopathology, serological studies) was recorded at 3, 6, 9 and 12 months of age. Detailed pituitary histological and immunohistochemical studies were performed at 12 months. RESULTS 12-month old Aip+/- mice demonstrated phenotypic and biochemical evidence of GH excess including significantly elevated IGF-1 levels, larger weight and body length, higher hemoglobin and cholesterol levels and a higher frequency of growth plate thickening in comparison to Aip+/, Prkar1a+/- mice. Pituitary histopathology did not uncover any pituitary adenomas or somatotroph hyperplasia in either group. CONCLUSIONS These results demonstrate a slow progression from elevated GH release to the formation of overt somatotropinomas in Aip+/- mice; the acromegalic phenotype of these mice is surprisingly ameliorated in Aip+/-, Prkar1a+/- mice. This highlights the complexities of interaction between AIP and the PKA pathway. Specifically targeting GH secretion rather than somatotroph proliferation may be an advantage in the medical treatment of AIP-dependent human acromegaly.
The karrikin signaling regulator SMAX1 controls Lotus japonicus root and root hair development by suppressing ethylene biosynthesis

Significance Plant seedlings depend on efficient development of roots and root hairs for anchorage to the ground and for rapidly reaching nutrients and water for survival and growth. We found that a negative regulator of a small-molecule signaling pathway called “karrikin signaling” plays an important role in regulating root growth of the legume Lotus japonicus. Mutants of this regulator called “SMAX1” have short primary roots and strongly elongated root hairs. This phenotype is caused by enhanced ethylene biosynthesis, which in the wild type is suppressed by SMAX1. Thus, karrikin signaling regulates ethylene biosynthesis to fine-tune root development. An evolutionarily ancient plant hormone receptor complex comprising the α/β-fold hydrolase receptor KARRIKIN INSENSITIVE 2 (KAI2) and the F-box protein MORE AXILLARY GROWTH 2 (MAX2) mediates a range of developmental responses to smoke-derived butenolides called karrikins (KARs) and to yet elusive endogenous KAI2 ligands (KLs). Degradation of SUPPRESSOR OF MAX2 1 (SMAX1) after ligand perception is considered to be a key step in KAR/KL signaling. However, molecular events which regulate plant development downstream of SMAX1 removal have not been identified. Here we show that Lotus japonicus SMAX1 is specifically degraded in the presence of KAI2 and MAX2 and plays an important role in regulating root and root hair development. smax1 mutants display very short primary roots and elongated root hairs. Their root transcriptome reveals elevated ethylene responses and expression of ACC Synthase 7 (ACS7), which encodes a rate-limiting enzyme in ethylene biosynthesis. smax1 mutants release increased amounts of ethylene and their root phenotype is rescued by treatment with ethylene biosynthesis and signaling inhibitors. KAR treatment induces ACS7 expression in a KAI2-dependent manner and root developmental responses to KAR treatment depend on ethylene signaling. Furthermore, in Arabidopsis, KAR-induced root hair elongation depends on ACS7. Thus, we reveal a connection between KAR/KL and ethylene signaling in which the KAR/KL signaling module (KAI2–MAX2–SMAX1) regulates the biosynthesis of ethylene to fine-tune root and root hair development, which are important for seedling establishment at the beginning of the plant life cycle.
Diabetes Impairs Cellular Cholesterol Efflux From ABCA1 to Small HDL Particles

Supplemental Digital Content is available in the text. Rationale: HDL (high-density lipoprotein) may be cardioprotective because it accepts cholesterol from macrophages via the cholesterol transport proteins ABCA1 (ATP-binding cassette transporter A1) and ABCG1 (ATP-binding cassette transporter G1). The ABCA1-specific cellular cholesterol efflux capacity (ABCA1 CEC) of HDL strongly and negatively associates with cardiovascular disease risk, but how diabetes mellitus impacts that step is unclear. Objective: To test the hypothesis that HDL’s cholesterol efflux capacity is impaired in subjects with type 2 diabetes mellitus. Methods and Results: We performed a case-control study with 19 subjects with type 2 diabetes mellitus and 20 control subjects. Three sizes of HDL particles, small HDL, medium HDL, and large HDL, were isolated by high-resolution size exclusion chromatography from study subjects. Then we assessed the ABCA1 CEC of equimolar concentrations of particles. Small HDL accounted for almost all of ABCA1 CEC activity of HDL. ABCA1 CEC―but not ABCG1 CEC―of small HDL was lower in the subjects with type 2 diabetes mellitus than the control subjects. Isotope dilution tandem mass spectrometry demonstrated that the concentration of SERPINA1 (serpin family A member 1) in small HDL was also lower in subjects with diabetes mellitus. Enriching small HDL with SERPINA1 enhanced ABCA1 CEC. Structural analysis of SERPINA1 identified 3 amphipathic α-helices clustered in the N-terminal domain of the protein; biochemical analyses demonstrated that SERPINA1 binds phospholipid vesicles. Conclusions: The ABCA1 CEC of small HDL is selectively impaired in type 2 diabetes mellitus, likely because of lower levels of SERPINA1. SERPINA1 contains a cluster of amphipathic α-helices that enable apolipoproteins to bind phospholipid and promote ABCA1 activity. Thus, impaired ABCA1 activity of small HDL particles deficient in SERPINA1 could increase cardiovascular disease risk in subjects with diabetes mellitus.
Leptin Sensitizes NTS Neurons to Vagal Input by Increasing Postsynaptic NMDA Receptor Currents

Leptin signaling within the nucleus of the solitary tract (NTS) contributes to the control of food intake, and injections of leptin into the NTS reduce meal size and increase the efficacy of vagus-mediated satiation signals. Leptin receptors (LepRs) are expressed by vagal afferents as well as by a population of NTS neurons. However, the electrophysiological properties of LepR-expressing NTS neurons have not been well characterized, and it is unclear how leptin might act on these neurons to reduce food intake. To address this question, we recorded from LepR-expressing neurons in horizontal brain slices containing the NTS from male and female LepR-Cre X Rosa-tdTomato mice. We found that the vast majority of NTS LepR neurons received monosynaptic innervation from vagal afferent fibers and LepR neurons exhibited large synaptic NMDA receptor (NMDAR)-mediated currents compared with non-LepR neurons. During high-frequency stimulation of vagal afferents, leptin increased the size of NMDAR-mediated currents, but not AMPAR-mediated currents. Leptin also increased the size of evoked EPSPs and the ability of low-intensity solitary tract stimulation to evoke action potentials in LepR neurons. These effects of leptin were blocked by bath applying a competitive NMDAR antagonist (DCPP-ene) or by an NMDAR channel blocker applied through the recording pipette (MK-801). Last, feeding studies using male rats demonstrate that intra-NTS injections of DCPP-ene attenuate reduction of overnight food intake following intra-NTS leptin injection. Our results suggest that leptin acts in the NTS to reduce food intake by increasing NMDAR-mediated currents, thus enhancing NTS sensitivity to vagal inputs. SIGNIFICANCE STATEMENT Leptin is a hormone that critically impacts food intake and energy homeostasis. The nucleus of the solitary tract (NTS) is activated by vagal afferents from the gastrointestinal tract, which promotes termination of a meal. Injection of leptin into the NTS inhibits food intake, while knockdown of leptin receptors (LepRs) in NTS neurons increases food intake. However, little was known about how leptin acts in the NTS neurons to inhibit food intake. We found that leptin increases the sensitivity of LepR-expressing neurons to vagal inputs by increasing NMDA receptor-mediated synaptic currents and that NTS NMDAR activation contributes to leptin-induced reduction of food intake. These findings suggest a novel mechanism by which leptin, acting in the NTS, could potentiate gastrointestinal satiation signals.
Biology of diamondback moth, Plutella xylostella (L.) on mustard in Laboratory

Studies on the biology of diamondback moth, Plutella xylostella (L.) (Lepidoptera: Yponomcutidae) in the laboratory revealed that incubation period ranged between 3.00 to 5.25 days and larval stage consisted of four instars with 3.74, 5.13, 5.60 and 5.61 days duration respectively for I, II, III and IV instar. The total larval duration ranged from 27.00 to 32.75 days with a mean of 29.86 days. The pupal period lasted for 3.50 to 4.75 days with a mean of 4.27 days and adult longevity was 4.27 days. The total developmental period from egg to adult ranged from 27.00 to 32.75 days. The fecundity was 55.14 eggs and the number of eggs laid were more on the lower surface of leaves.
Proximal and contextual correlates of childhood stunting in India: A geo-spatial analysis

Background Globally, India is home to every third child affected by stunting. While numerous studies have examined the correlates of childhood stunting (CS) in India, most of these studies have focused on examining the role of proximal factors, and the role of contextual factors is much less studied. This study presents a comprehensive picture of both proximal and contextual determinants of CS in India, expanding the current evidence base. The present study is guided by the WHO conceptual framework, which outlines the context, causes, and consequences of CS. Data and methods The study used exploratory spatial data analysis tools to analyse the spatial pattern and correlates of CS, using data from the fourth round (2015–16) of the National Family Health Survey (NFHS-4) and the 2011 Census of India. Results The study findings reiterate that CS continues to be high in India, with several hot spot states and districts, and that children from the central and eastern region of the nation, namely, Bihar, Jharkhand, Madhya Pradesh, and Uttar Pradesh are particularly vulnerable. Our analysis has identified six risk factors—maternal short stature, large household size, closely spaced births, prevalence of hypertension among women, household poverty, open defecation, and extreme temperature—and four protective factors—female education, access to improved drinking water, dietary diversity among children, and iron and folic acid (IFA) supplementation during pregnancy. Conclusions The study highlights the need for investing in pre-conception care, addressing both demand- and supply-side barriers to increase the coverage of nutrition-specific interventions, implementing programmes to promote the intake of healthy foods from an early age, providing contraceptive counselling and services to unmarried and married adolescents and young women and men, and universalizing quality primary and secondary education that is inclusive and equitable to avert the burden of childhood stunting in India.