A novel respiratory pathogen, SARS-CoV-2 has recently received worldwide attention and has been declared a public health emergency of global concern. Entry of SARS-CoV-2 is mediated through the viral spike glycoprotein (S2). Afterwards, the virus gets hold of the host cell machinery by employing the use of viral main protease 3CLpro and NSP15 endoribonuclease. In the present in silico study, active site mapping of the viral virulence factors was rendered by means of DoG Site Scorer. The possibility of repurposing of 2-deoxy-D-glucose (2-DG), a radio-chemo-modifier drug used for optimizing cancer therapy, and one of its derivative (1, 3, 4, 6-Tetra-O-acetyl-2-deoxy-D-glucopyranose, has been investigated by conducting ligand-receptor docking. Binding pose depictions of ligands and viral receptors were assessed by employing molecular dynamics analysis. Molinspiration and Toxicity Estimation Software tools were used to assess the drug likeliness, bioactivity indices and ADMETox values. 2-DG can dock efficiently with viral main protease 3CLpro as well as NSP15 endoribonuclease, thus efficiently inactivating these viral receptors leading to incapacitation of the SARS-CoV-2 virus. Such incapacitation was possible by means of formation of a hydrogen bond between 2-DG and proline residues of viral protease. The 2-DG derivative formed a hydrogen bond with the glutamine amino acid residues of the viral spike glycoprotein. The present in silico study supports the potential benefits of using 2-DG and its glucopyranose derivative as repurposed drugs/prodrugs for mitigating the novel COVID-19 infection. Since both these moieties present no signs of serious toxicity, further empirical studies on model systems and human clinical trials to ascertain effective dose-response are warranted and should be urgently initiated.

Behcet’s disease (BD) is a vasculitis of unknown aetiology that is reported to accompany autoimmune diseases. We report a rare case of BD, Addison’s disease, Hashimoto’s disease, and subclinical coeliac disease all occurring in one patient which has not previously been reported.

Eosinophilic gastroenteritis (EG) can easily be misdiagnosed. We present the case of a man with abdominal pain who was EG but misdiagnosed with cholelithiasis. This case highlights the need to consider EG in the differential diagnosis of abdominal pain since a favorable result can be achieved with timely treatment.

Chlamydia psittaci is an intracellular organism causing psittacosis which is found in psittacine birds and can be transmitted to humans by inhalation or direct contact. Here we present a case of human psittacosis mimicing acute monocytic leukemia which demonstrates an extraordinary clinical presentation of psittacosis.

The study assesses rice yield response to levels of agrochemical use in Ghana. We employed the Dose-Response Model Approach under continuous and heterogeneous responses to treatment. The dose-response model of rice yield with chemical fertilizer treatment indicates that averagely, chemical fertilizer use is associated with a 10% kilograms per hectare surge in rice yield. This upsurge in rice yield subsequently reduces and turns out to be immaterial as chemical fertilizer quantities move from 20% to 70% and afterwards increases. On the other hand, the dose-response function of rice yield with herbicides treatment shows that, averagely, herbicide use is related to a 7% kg/ha rise in rice yield. This increase in rice yield reduces substantially as herbicides volumes move from 40% to 100%. It can be concluded that rice yield responds to an increase in the intensity of use of chemical fertilizer but not herbicides. The implication is that even though the Green Revolution agricultural technologies were meant to be adopted as a package, their right mix in terms of levels or intensity is also critical.

Immune suppression during pregnancy and parturition is considered a risk factor that is related to the progression of bovine chronic diseases, such as bovine leukosis, which are caused by bovine leukemia virus (BLV). Our previous studies have demonstrated that prostaglandin E2 (PGE2) suppresses BLV-specific Th1 responses and contributes to the disease progression during BLV infection. Although PGE2 reportedly plays important roles in the induction of parturition, PGE2 involvement in immune suppression during parturition is unknown. To investigate its involvement, we analyzed PGE2 kinetics and Th1 responses in BLV-infected pregnant cattle. PGE2 concentrations in sera were increased, whereas IFN-γ responses were decreased before delivery. PGE2 is known to suppress Th1 immune responses in cattle. Thus, these data suggest that PGE2 upregulation inhibits Th1 responses during parturition. We also found that estradiol was important for PGE2 induction in pregnant cattle. In vitro analyses indicated that estradiol suppressed IFN-γ production, at least in part, via PGE2/EP4 signaling. In vivo analyses showed that estradiol administration significantly influenced the induction of PGE2 production and impaired Th1 responses. Our data suggest that estradiol-induced PGE2 is involved in the suppression of Th1 responses during pregnancy and parturition in cattle, which could contribute to the progression of BLV infection.

Tumour antigens and other lymphocyte-activating factors, such as IFN-γ, can induce PD-1 expression, The combination of PD-1 with PD-L1 has negative effects on activation, proliferation and cytotoxicity of T lymphocytes. The use of a PD-1/PD-L1 blocking strategy has produced some achievements in solid tumours. The immune checkpoints related to blocking therapy ultimately depend on T cells to express an effect. It is unclear Whether interaction between T cells and hepatoma cells on different backgrounds affects PD1 or PDL1 expression,It is also unclear whether there is a difference between the killing effect of knocking out PD-1 receptors and that of blocking the PD-1 pathway with monoclonal antibodies on hepatoma cells with different backgrounds . In this study, the interactions between expression of PD-1/PD-L1 were observed by coculturing umbilical cord blood derived NKT cells with hepatoma cell lines on different backgrounds (MHCC97H,HepG2, SMMC-7721 and Huh-7), Furthermore, the killing effect of NKT cells targeting tumor cells were investigated after knocking out PD-1 on NKT cells or applying monoclonal antibodies to block PD-1. Our results showed that Coculture of hepatoma cells with NKT cells mutually affected the expression of PD-L1 and PD-1;Hepatoma cells in different genetic lines respond to NKT-cell-induced PD-L1 stimulats differently, and those tumor cells with lower PDL1 expression fail to PD1 blocking intervention; The killing effect was more time-efficient with PD-1 knockout than with monoclonal antibody blockade, although it only advanced one or two weeks.

What is precision medicine? No standard definition is found. Sometimes described as High Definition Medicine which is: “the dynamic assessment , management, and understanding of an individual’s health measured at (or near) its most basic units.” The impetus for this venture was advanced and stimulated by biogenetics, the study of how genes and their products affect health but also contribute to disease or resistance to cure. Medicine is an epistemology: a way of knowing, perceiving, remembering, finding out, proving, inferring, wondering, reflecting, a conceptual knowing relying upon observations fitted to disease concepts.

Background: Hypertensive disorders of pregnancy affects uteroplacental and fetoplacental perfusion and may result into poor fetal conditions and increase perinatal morbidity and mortality. Aim: To study how effective CCBs are in improving uteroplacental perfusion. Material and methodology: 120 pregnant women with the gestation ages ranging from 32-40 weeks. Among them sixty were having hypertensive disorders of pregnancy and sixty were normal pregnant women. In case groups blood pressure before and after at least one of medication were recorded, and Doppler ultrasound indices for fetal MCA and UA S/D after at least one week of medication was also recorded. Results: MCA Peak systolic speed, UA S/D ratio, MCA Pulsatile index and MCA resistance index mean values differences between the two groups were not statistically significant i.e. p-value >0.05 . In correlation with p-value<0.05,and measured : PS was affected by gestation age (1.63) , S/D ratio was affected by gestation age(-0.1), systolic blood pressure (0.013) and age of women (0.007), PI on the other hand was impacted by gravidity(0.07) and preeclampsia(0.20). RI showed correlation with chronic hypertension (-0.08). on outcomes of pregnancy there was a relationship between S/D and Apgar score, an increase of S/D was associated with decrease of Apgar score, (-0.16,95% CI=-0.27 to 0.05, p-value=0.06). Conclusion: Oral use of nifedipine as an antihypertensive of choice in managing hypertensive disorders of pregnancy seem to improve uteroplacental perfusion in women with hypertensive disorders of pregnancy.

COVID-19 has emerged as a new viral illness with potential for significant morbidity and mortality. Pregnant women are high risk for contracting the virus or suffering from complications, however data regarding the effect of COVID-19 on pregnancy is limited to case reports from affected countries. The pathophysiology of COVID-19 infection may provide insights of the threat to mother and fetus. In this review we collate available evidence of harm caused by COVID-19 to mothers and their offspring in all trimesters. Obstetricians must understand the risks posed by this pandemic to effectively counsel women who are currently pregnant or planning conception.

Since end of December 2019, a cluster of patients with pneumonia of unknown origin was reported from Wuhan, Hubei province, China. They shared a connection with the Huanan South China Seafood Market in Wuhan, and now it has been confirmed that the disease is caused by a novel coronavirus (officially named COVID-19). According to real-time statistics from Johns Hopkins University in the United States, as of 5:30 on the 31st, Beijing time, the number of confirmed cases of COVID-19 pneumonia in the world has exceeded 770,000, reaching 777,286, and the number of deaths has reached 37,140. Currently, clinicians have found some atypical cases with positive chest CT findings may present with negative results of RT-PCR for COVID-19. The timely diagnosis, isolation and treatment of these patients will help control the further spread of COVID-19.

Leaf shape is a defining feature of how we recognise and classify plant species. Although there is extensive variation in leaf shape within many species, few studies have disentangled the underlying genetic architecture. We characterised the genetic architecture of leaf shape variation in Eurasian aspen (Populus tremula L.) by performing a genome wide association studies (GWAS) for physiognomy traits. To ascertain the roles of identified GWAS candidate genes within the leaf development transcriptional program, we performed gene co-expression network analyses from a developmental series, which is publicly available at http://aspleaf.plantgenie.org. We additionally used gene expression measurements across the population to analyse GWAS candidate genes in the context of a population-wide co-expression network and to identify genes that were differentially expressed between groups of individuals with contrasting leaf shapes. These data were integrated with expression GWAS (eQTL) results to define a set of candidate genes associated with leaf shape variation. Our results identified no clear adaptive link to leaf shape variation and indicate that leaf shape traits are genetically complex, likely determined by numerous small-effect variations in gene expression. Genes associated with shape variation were peripheral within the population-wide co-expression network, were not highly connected within the leaf development co-expression network and exhibited signatures of relaxed selection. As such, our results are consistent with the omnigenic model.

Siberian larch (Larix Mill.) forests dominate vast areas of northern Russia and contribute important ecosystem services to the world. It is important to understand the past dynamics of larches, in order to predict their likely response to a changing climate in the future. Sedimentary ancient DNA extracted from lake sediment cores can serve as archives to study past vegetation. However, the traditional method of studying sedimentary ancient DNA – metabarcoding – focuses on small fragments which cannot resolve Larix to species level nor allow the detailed study of population dynamics. Here we use shotgun sequencing and hybridization capture with long-range PCR-generated baits covering the complete Larix chloroplast genome to study Larix populations from a sediment core reaching back up to 6700 years in age from the Taymyr region in northern Siberia. In comparison to shotgun sequencing, hybridization capture results in an increase of taxonomically classified reads by several orders of magnitude and the recovery of near-complete chloroplast genomes of Larix. Variation in the chloroplast reads corroborate an invasion of Larix gmelinii into the range of Larix sibirica before 6700 years ago. Since then, both species have been present at the site, although larch populations have decreased with only a few trees remaining in what was once a forested area. This study demonstrates for the first time that hybridization capture applied to ancient DNA from lake sediments can provide genome-scale information and is a viable tool for studying past changes of a specific taxon.

The Spruce and Peatland Responses Under Changing Environments (SPRUCE) project is a warming and elevated carbon dioxide (CO2) experiment designed to test how peatland ecosystems will respond to climate change. Here, we report changes in the vascular plant community during the first five years of SPRUCE. We tracked species composition, diversity, and aboveground net primary production (ANPP) in chambers warmed at a wide range of temperatures (+0, +2.25, +4.5, +6.75, +9 ˚C), and two CO2 levels (~400 [ambient] and 900 parts per million). We observed an increase in aboveground vascular plant biomass accumulation, due primarily to an increase in shrub abundances. Overall species diversity decreased substantially, likely due in part to shading by a denser shrub canopy. These results indicate an overall increase in NPP with warming, but highlight the importance of interactions between direct (warming) and indirect (competition) effects in determining how boreal ecosystems will respond to climate change.

Intravenous immunoglobulin (IVIGs) preparations, which are used in the treatment of many immune-based diseases, also have an important place in hematology practice. It is an important treatment option with many different immunoregulatory roles. There is a limitation of its use on adult patients due to the lack of retrospective data. In our study, the retrospective usage indications, responses and rates of IVIG preparations evaluated in our Hematology Clinic and used in various indications between January 2010 and January 2020 were attempted to be put forth. Our targets for treatment responses were as follows: For immune thrombocytopenia, the platelet count target was 30000 x 103/µL and above; no hospitalization need for secondary hypogammaglobulinemia; no replacement need for hemolytic anemia after IVIG and a hemoglobin level above 8 g/dl. When 166 patients were examined in total, 66 were diagnosed with immune thrombocytopenic purpura (ITP) (39.8%) . There were emergency indications for all patients with thrombocytopenia before getting a primary diagnosis. The number of patients who used IVIG before getting a primary diagnosis was 79 (47.6%), 41 of whom (51.9%) were diagnosed with immune thrombocytopenic purpura in follow up. The expected response was 36.1% with 60 patients within the entire patient group. With further examination performed after emergency usage, the diagnoses received by the patients were revealed. The response was 58.5% with 24 patients in whom IVIG was used under emergency conditions and deep thrombocytopenia before getting a primary diagnosis and were diagnosed with ITP after further examinations

Atmospheric deposition of nitrogen (N) compounds have significantly increased worldwide in the recent decades, mainly in the form of ammonium (NH4+-N), nitrate (NO3−-N) and urea (CO(NH2)2). Here, we used meta-analysis to compare the influence of different N types on terrestrial soil microbial biomass based on 1585 paired observations from 178 articles. In all N types, NH4+-N addition displayed the greatest negative affects on soil microbial biomass (-18.9 %) followed by. NH4NO3 (-7.51 %) and NO3−-N (-7.26 %). CO(NH2)2 addition resulted in the smallest total microbial biomass declines among all N types (-6.99 %). All the soil microbial characteristics, such as fungi and bacteria, revealed the same trends across all ecosystems, especially for arbuscular mycorrhizal fungi, F/B, and G+/G− ratio. In addition, the response sizes were significantly correlated with the accumulated N amount (N addition rate × application duration). The results indicated that the response sizes were significantly N-type dependent.

An Unusual Clustered Series of Foreign Body Reactions to Oxidised Regenerated Cellulose in Head and Neck surgery - A Case series of four post-operative patients

4 nucleotides(A, U, C, G) constitute 64 codons at free combination but 64 codons are unequally assigned to 21 items (20 amino acids plus one stop). About 500 amino acids are known but only 20 ones are selected to make up the proteins. However, the relationships between amino acid and codon and between 20 amino acids have been unclear. In this paper, we studied on the relationships between 20 amino acids in 33 species and found there were three constraints between 20 amino acids, such as the relatively stable mean carbon and hydrogen(C:H) ratios(0.50), similarity interactions between the constituent ratios of amino acids, and the frequency of amino acids according with Poisson distribution under a certain conditions. We demonstrated that the unequal distribution of 64 codons and the choice of amino acids in molecular evolution would be constrained to remain stable C:H ratios. The constituent ratios and frequency of 20 amino acids in a species or a protein are two determinants of protein sequence evolution, so this findings showed the constraints between 20 amino acids played an important role in protein sequence evolution.

The bZIP family is one of the most widely distributed and conserved transcription factor categories in eukaryotes. They are widely involved in processes of plant abiotic stress responses, such as improving the ability of plants to adapt to drought, salinity and cold. To comprehensively understand how plant bZIPs regulating these tolerances, this article will have an overview of their distributions on different species, characteristics of protein architecture, regulation mechanisms for target genes' transcriptional expression, and relevant research progresses in recent years. Specially, we will discuss the possible roles of flavonoids, whose synthesis could be regulated by bZIPs, in abovementioned plant tolerant responses.

BACKGROUND AND PURPOSE PP242, an inhibitor of mechanistic target of rapamycin (mTOR), displays potent anticancer effects against various types of cancer. However, the underlying metabolic mechanism associated with the PP242 effects is not clearly understood. In this study, comprehensive metabolomics and lipidomics investigations were performed in plasma and tumor tissue to reveal the metabolic mechanism of PP242 in an LS174T cell-induced colon cancer xenograft mouse model. EXPERIMENTAL APPROACH A colon cancer xenograft model was developed in BALB/c nude mice and then treated with PP242 for three weeks. After the final dose, blood, tumor, liver and kidney tissues were collected. Plasma and tumor samples were analyzed through untargeted metabolomics and lipidomics approaches using ultra-high-performance chromatography-Orbitrap-mass spectrometry (UHPLC-Orbitrap-MS). KEY RESULTS PP242 treatment reduces tumor size without any critical toxicities. According to results, metabolic changes due to the effects of PP242 were not significant in plasma. In contrast, metabolic changes in tumor tissues were very significant in the PP242-treated group compared to the xenograft control (XC) group, and revealed that energy and lipid metabolism were mainly altered by PP242 treatment like other cancer inhibitors. Additionally, it this study it was discovered that not only TCA cycle but also fatty acid β-oxidation (β-FAO) for energy metabolism was inhibited and clear reduction in glycerophospholipid was observed. CONCLUSIONS AND IMPLICATIONS The findings of this study reveal new insights into the underlying anticancer mechanism of the dual mTOR inhibitor PP242, and could help further facilitate the understanding of the effects PP242 in the course of clinical application.

Background and Purpose: 5-Fluorouracil (5-FU)-based chemotherapy is the first-line chemotherapeutic agent for colorectal cancer. However, 5-FU–induced intestinal mucositis (FUIIM) is a common adverse effect that severely impairs drug tolerance and results in poor patient health. Experimental Approach: Neutrophil elastase (NE) overexpression contributes to FUIIM via abnormal inflammatory responses, microbiota imbalance, and tissue damage. Therefore, restoring NE homeostasis could prevent or improve FUIIM. Key Results: This study shows that treatment with the specific NE inhibitor MPH966 (7.5 mg/kg; p.o.) significantly reversed 5-FU–induced losses in body weight; reversed villus atrophy; significantly suppressed myeloperoxidase, NE, and proteinase 3 activity; and reduced pro-inflammatory cytokine levels in a mouse model of FUIIM. In addition, MPH966 prevented 5-FU–induced intestinal barrier dysfunction, as was indicated by modulated expression of the tight junction proteins zonula occludin-1 and occludin. MPH966 also reversed 5-FU–induced changes in gut microbiota diversity and abundances, specifically the Firmicutes-to-Bacteroidetes ratio; Muribaculaceae, Ruminococcaceae, and Eggerthellaceae abundances at the family level; and Candidatus Arthromitus abundance at the genus level. Conclusion and Implications: These data indicate that NE inhibitors are a potential treatment candidate to alleviate FUIIM by regulating abnormal inflammatory responses, intestinal barrier dysfunction, and gut microbiota imbalance.

Different Ailanthus excelsa based agroforestry systems (Bund/boundary, scattered trees in the existing farming systems) are practiced by the farmers in dry parts of north-west India. However, modern/improved A. excelsa based agroforestry systems are not popular among the farmers. Therefore, in this study improved A. excelsa based agroforestry systems with different tree densities were developed and assessed during initial years of establishment in nutrient poor, light textured soils to enhance soil fertility and productivity. In the present study, the yields of agricultural crops were not influenced by A. excesla trees, irrespective of crop or tree geometry/density. This might be due to young age of A. excelsa trees. However, soil fertility status in terms of organic matter, available P and K improved under agroforestry systems as compared to sole cropping. Growth performance of A. excelsa under different tree densities and in association with crops was statistically at par. Maximum girth (47.10 cm) at breast height was recorded under 10 x 20 m spacing with cluster bean-wheat sequence, but it was at par with other treatments. Maximum carbon sequestration (9.64 t ha-1 year-1) was recorded in A. excelsa + cluster bean – wheat agroforestry system with 200 trees/ha. Cluster bean – wheat crop sequence sequestered more carbon as compared to pearl millet- Indian mustard. A. excelsa based agroforestry systems fetched higher net returns as compared to sole cropping. Two years experimentation showed maximum benefits under agroforestry with 10 x 5 spacing under both the crop sequences.

A semiclassical phase-space perspective of band- and topological-insulator regimes of 2D Dirac materials, and normal- and superradiant-phases of atom-field interacting models is given in terms of delocalization, entropies, and quantum correlation measures. From this point of view, the low-energy limit of tight-binding models describing the electronic band structure of topological 2D Dirac materials like phosphorene and silicene with tunable band gaps, share similarities with Rabi-Dicke and Jaynes-Cummings atom-field interaction models, respectively. In particular, the edge state of 2D Dirac materials in the topological insulator phase exhibits a Schr\”odinger cat structure similar to the ground state of two-level atoms in a cavity interacting with a one-mode radiation field in the superradiant phase. Delocalization seems to be a common feature of topological insulator and superradiant phases.

Objective: Stress urinary incontinence is a common health problem, with grave social and economic consequences, that is associated with a reduced quality of life. Stem cell therapy has developed as a novel modality for regeneration of injured tissues and could be a promising strategy for treatment of stress urinary incontinence. The objective of this systematic review is to summarize the clinical trials available to date, on stem cells therapy for treatment of stress urinary incontinence in woman. Study design: PubMed, Cochrane Library, Scopus and Embase were searched for studies published until January 2020 on Stem cell therapy for Stress urinary incontinence in woman. Quality of the included studies was assessed formally and independently by two authors using the JBI Critical Appraisal Checklists according to the PRISMA guidelines. Results: 19 studies were included and their quality was assessed with the JBI Critical Appraisal Checklists. These studies imply that stem cells therapy for treatment of stress urinary incontinence is a safe and effective treatment. Conclusions: While it is difficult to draw specific conclusions, initial results of stem cell therapy for the treatment of stress urinary incontinence seem encouraging. The great variability in cell types, injection protocols, follow up duration and evaluation tests, outcome measures and adverse effects indicates the need for standardization and validation of this treatment modality before it could be recommended for routine use.