Effect of early oxygen therapy and antiviral treatment on disease progression in patients with COVID-19: A retrospective study of medical charts in China

BackgroundUntil now, no antiviral treatment has been proven to be effective for the coronavirus disease 2019 (COVID-19). The timing of oxygen therapy was considered to have a great influence on the symptomatic relief of hypoxemia and seeking medical intervention, especially in situations with insufficient medical resources, but the evidence on the timing of oxygen therapy is limited.Methods and findingsMedical charts review was carried out to collect the data of hospitalized patients with COVID-19 infection confirmed in Tongji hospital, Wuhan from 30^th December 2019 to 8^th March 2020. In this study, the appropriate timing of oxygen therapy and risk factors associated with severe and fatal illness were identified and the effectiveness of antivirus on disease progression was assessed. Among 1362 patients, the prevalence of hypoxia symptoms was significantly higher in those patients with severe and fatal illness than in those with less severe disease. The onset of hypoxia symptoms was most common in the second to third week after symptom onset, and patients with critical and fatal illness experienced these symptoms earlier than those with mild and severe illness. In multivariable analyses, the risk of death increased significantly when oxygen therapy was started more than 2 days after hypoxia symptoms onset among critical patients (OR, 1.92; 95%CI, 1.20 to 3.10). Compared to the critically ill patients without IFN-a, the patients who were treated with IFN-a had a lower mortality (OR, 0.60; 95%CI, 0.39 to 0.91).ConclusionsEarly initiation of oxygen therapy was associated with lower mortality among critical patients. This study highlighted the importance of early oxygen therapy after the onset of hypoxia symptoms. Our results also lend support to potentially beneficial effects of IFNα on critical illness.     

Population genetic structure of sharpbelly Hemiculter leucisculus (Basilesky, 1855) and morphological diversification along climate gradients in China

Sharpbelly Hemiculter leucisculus (Basilewski, 1855) is a small, widespread, and native cyprinid fish with prominent habitat suitability and high invasive potential and is becoming the dominant species in freshwater ecosystems under intensified environmental disturbances. But how H. leucisculus acclimates to extremely heterogeneous environments remains unclear. In current study, the genetic structure of H. leucisculus was analyzed using Bayesian phylogenetic inference, haplotype network, and STRUCTURE base on cytb gene across 18 populations spanning 20 degrees of latitude and 18 degrees of longitude in China. The morphological diversification of body size and shape for H. leucisculus along the climate gradient was studied. The results showed that the 18 H. leucisculus populations were divided into 3 clusters: one cluster mainly from Huanghe River Basin, another cluster mainly from Yangzi River Basin, and H cluster containing Hainan and Beihai populations. The fish from southern populations were deeper bodied while individuals from northern populations were more slender. Inland individuals were more streamlined while coastal individuals were of deeper body. The partial Mantel test predicts that the potential mechanism underlining the intraspecies morphological diversification along climate gradients is primarily the divergent selection pressures among different environments, while genetic variation had less contribution to morphological differentiation. The formation of the Nanling Mountain Range could drive genetic differentiation between Beihai population and those from Yangzi River Basin. The present results highlight strong selective pressures of climate on widespread species and enrich morphological differentiation basis of acclimation for species with high habitat suitability and invasive potential.     

Pancreatic stellate cell-derived exosomal tRF-19-PNR8YPJZ promotes proliferation and mobility of pancreatic cancer through AXIN2

The pancreatic stellate cells (PSCs) play an important role in the development of pancreatic cancer (PC) through mechanisms that remain unclear. Exosomes secreted from PSCs act as mediators for communication in PC. This study aimed to explore the role of PSC-derived exosomal small RNAs derived from tRNAs (tDRs) in PC cells. Exosomes from PSCs were extracted and used to detect their effects on PC cell proliferation, migration and invasion. Exosomal tDRs profiling was performed to identify PSC-derived exosomal tDRs. ISH and qRT-PCR were used to examine the tRF-19-PNR8YPJZ levels and clinical value in clinical samples. The biological function of exosomal tRF-19-PNR8YPJZ was determined using the CCK-8, clone formation, wound healing and transwell assays, subcutaneous tumour formation and lung metastatic models. The relationship between the selected exosomal tRF-19-PNR8YPJZ and AXIN2 was determined by RNA sequencing, luciferase reporter assay. PSC-derived exosomes promoted the proliferation, migration, and invasion of PC cells. Novel and abundant tDRs are found to be differentially expressed in PANC-1 cells after treatment with PSC-derived exosomes, such as tRF-19-PNR8YPJZ. PC tissue samples showed markedly higher levels of tRF-19-PNR8YPJZ than normal controls. Patients with PC exhibiting high tRF-19-PNR8YPJZ expression had a highly lymph node invasion, metastasis, perineural invasion, advanced clinical stage and poor overall survival. Exosomal tRF-19-PNR8YPJZ from PSCs targeted AXIN2 in PC cells and decreased its expression, thus activating the Wnt pathway and promoting proliferation and metastasis. Exosomal tRF-19-PNR8YPJZ from PSCs promoted proliferation and metastasis in PC cells via AXIN2.     

Biomass yield in a genetically diverse Miscanthus sacchariflorus germplasm panel phenotyped at five locations in Asia,North America,and Europe

Miscanthus is a high-yielding bioenergy crop that is broadly adapted to temperate and tropical environments. Commercial cultivation of Miscanthus is predominantly limited to a single sterile triploid clone of Miscanthus × giganteus, a hybrid between Miscanthus sacchariflorus and M. sinensis. To expand the genetic base of M. × giganteus, the substantial diversity within its progenitor species should be used for cultivar improvement and diversification. Here, we phenotyped a diversity panel of 605 M. sacchariflorus from six previously described genetic groups and 27 M. × giganteus genotypes for dry biomass yield and 16 yield-component traits, in field trials grown over 3 years at one subtropical location (Zhuji, China) and four temperate locations (Foulum, Denmark; Sapporo, Japan; Urbana, Illinois; and Chuncheon, South Korea). There was considerable diversity in yield and yield-component traits among and within genetic groups of M. sacchariflorus, and across the five locations. Biomass yield of M. sacchariflorus ranged from 0.003 to 34.0 Mg ha⁻¹ in year 3. Variation among the genetic groups was typically greater than within, so selection of genetic group should be an important first step for breeding with M. sacchariflorus. The Yangtze 2x genetic group (=ssp. lutarioriparius) of M. sacchariflorus had the tallest and thickest culms at all locations tested. Notably, the Yangtze 2x genetic group's exceptional culm length and yield potential were driven primarily by a large number of nodes (>29 nodes culm⁻¹ average over all locations), which was consistent with the especially late flowering of this group. The S Japan 4x, the N China/Korea/Russia 4x, and the N China 2x genetic groups were also promising genetic resources for biomass yield, culm length, and culm thickness, especially for temperate environments. Culm length was the best indicator of yield potential in M. sacchariflorus. These results will inform breeders' selection of M. sacchariflorus genotypes for population improvement and adaptation to target production environments.     

Molecular Characterization of U6 Promoters from Orange-Spotted Grouper (Epinephelus coioides) and Its Application in DNA Vector-Based RNAi Technology

Marine Biotechnology - The U6 promoter, a typical RNA polymerase III promoter, is widely used to transcribe small RNAs in vector-based siRNA systems. The RNAi efficiency is mainly dependent on the...     

Constructing an initial map of transmission distortion based on high density HapMap SNPs across the human autosomes

Transmission distortion （TD） is a significant departure from Mendelian predictions of genes or chromosomes to offspring. While many biological processes have been implicated, there is still much to be understood about TD in humans. Here we present our findings from a genome-wide scan for evidence of TD using haplotype data of 60 trio families from the International HapMap Project. Fisher＇s exact test was applied to assess the extent of TD in 629,958 SNPs across the autosomes. Based on the empirical distribution of PFisher and further permutation tests, we identified 1,205 outlier loci and 224 candidate genes with TD. Using the PANTHER gene ontology database, we found 19 categories of biological processes with an enrichment of candidate genes. In particular, the “protein phosphorylation” category contained the largest number of candidates in both HapMap samples. Further analysis uncovered an intriguing non-synonymous change in PPPIR12B, a gene related to protein phosphorylation, which appears to influence the allele transmission from male parents in the YRI （Yoruba from Ibadan, Nigeria） population. Our findings also indicate an ethnicity-related property of TD signatures in HapMap samples and provide new clues for our understanding of TD in humans.     

Synthesis,resolution, and chiroptical properties of hemicryptophane cage controlling the chirality of propeller arrangement of a C3 triamide unit

The five‐steps synthesis of a hemicryptophane cage combining a benzene‐1,3,5‐tricarboxamide unit and a cyclotriveratrylene (CTV) moiety is described. Chiral high‐performance liquid chromatography (HPLC) was used to resolve the racemic mixture. The absolute configuration of the isolated enantiomers was assigned by comparison of the experimental electronic circular dichroism (ECD) spectra with the calculated ones. X‐ray molecular structures reveal that the capped benzene‐1,3,5‐tricarboxamide unit adopts a structurally chiral conformation in solid state: the chirality of CTV moiety controls the Λ or Δ orientation of the three amides.     

A New Quinolone and Other Constituents from the Fruits of Tetradium ruticarpum: Effects on Neutrophil Pro‐Inflammatory Responses

The fruit of Tetradium ruticarpum is widely used in healthcare products for the improvement of blood circulation, headache, abdominal pain, amenorrhea, chill limbs, migraine, and nausea. A new quinolone, 2‐[(6Z,9Z)‐pentadeca‐6,9‐dienyl]quinolin‐4(1H)‐one ( 1 ), has been isolated from the fruits of T. ruticarpum, together with eleven known compounds. The structure of the new compound was determined by NMR and MS analyses. Rutaecarpine ( 4 ), evodiamine ( 5 ), and skimmianine ( 7 ) exhibited inhibition (IC₅₀≤20.9 μM ) of O$\rm{{_{2}^{{^\cdot} -}}}$ generation by human neutrophils in response to N‐formyl‐L ‐methionyl‐L ‐leucyl‐L ‐phenylalanine/cytochalasin B (fMLP/CB). In addition, 1 , evocarpine ( 2 ), 4, 7 , and evodol ( 8 ) inhibited fMLP/CB‐induced elastase release with IC₅₀ values ≤14.4 μM .