Seasonal dormancy (e.g. diapause, hibernation) is widely considered an adaptation for surviving life-threatening conditions during part of the year. However, the selective pressures acting on dormancy are poorly studied. An underestimated common aspect is the high survival rate during dormancy compared to the active period, perhaps due to the reduced risk of predation and competition. We hypothesize that dormancy phenology is influenced by a trade-off between the reproductive benefits of being active and the survival benefits of being dormant. Using a phylogenetic comparative method and more than 20 hibernating mammals, we find that the sex difference in hibernation phenology is explained by sex differences in physiological constraints that may influence this trade-off. Consistent with the trade-off hypothesis, the sex that spends more time in an activity directly associated with reproduction (e.g. testicular maturation, gestation) or indirectly (e.g. recovery from reproductive stress) spends less time in hibernation. Some of the tested parameters such as testes maturation or a late mating period during the active season also influence the sex difference in dormancy phenology among ectotherms (e.g. reptiles, invertebrates). We then gathered evidence that dormancy in non-life-threatening periods that are unfavorable for reproduction may be more widespread than previously thought.

A 74-year-old female presented with COVID-19 pneumonia and multinodular goiter with right lobe enlargement, occupying medium mediastinum with trachea compression is presented. COVID-19 pro-thrombotic status combined with low dynamic flow due to the large goiter resulted in deep vein thrombosis of subclavian and jugular veins in this case.

Increasing numbers of papers, blogs and advocacy campaigns correctly observe that freshwater biodiversity (in its hierarchical construct) is declining rapidly. But there are also authors expressing the same views for other ecosystems. The result is this special pleading, separating freshwater biodiversity from the rest of terrestrial biodiversity, produces a distorted picture of the research and actions needed to develop informed policy and decision-making, and thus improved stewardship of freshwaters. A key issue for effective and informed stewardship of freshwater biodiversity is promoting a research focus through the integrated lens of landscape connectivity and ecohydrology. Co-designing such integrated research that recognises the four-dimensional nature of freshwater ecosystems with early input from policymakers, decision-takers and holders of indigenous and local knowledge can result in a reversal of the decline seen in freshwater biodiversity. And in turn, better support for linked “terrestrial” biodiversity.

Prolonged prothrombin time (PT) and/or activated partial thromboplastin time (aPTT) are frequently seen in newly diagnosed pediatric leukemia patients (NDPLP), which can lead to delayed diagnostic and therapeutic procedures due to concern for bleeding. In this single center retrospective study of NDPLP we analyzed these parameters in 93 patients (aged 1-21 years). None had a personal history of bleeding, but 33.3% had bleeding symptoms within 30 days of presentation, predominantly mucosal bleeding (80.6%) and petechiae (64.5%). Median laboratory values at diagnosis: white blood cell count 15.7, hemoglobin 8.1, platelets 64, PT 13.2, and a PTT 31. Red blood cells were administered in 41.2%, platelets in 52.9%, FFP in 7.8%, and vitamin K in 21.6% based on institutional cut-off values for replacement or clinical symptoms. Prolonged PT was found in 54.8% of patients (factor VII 33.1% (interquartile range [IQR] 19.4-50.5), while aPTT was prolonged in 5.4%. Anemia and thrombocytopenia did not correlate with prolonged PT (p=0.73 and p=0.18 respectively), or prolonged aPTT (p=0.52 and 0.42). Leukocytosis and neutrophilia showed significant correlation with elevated PT (p<0.001 and <0.01 respectively), but not aPTT (p=0.3 and 0.5). Bleeding symptoms upon presentation did not correlate with prolonged PT (p=0.83), prolonged aPTT (p=1) or anemia (p=0.06) but had significant correlation with thrombocytopenia (p=<0.0001) and elevated AST (p=0.05). Therefore, a prolonged PT in NDPLP may not necessitate the reflexive use of blood product replacement in the absence of significant bleeding, which is likely related to leukocytosis than to a true coagulopathy.

The demand for particle board has been increasing over the years. Currently, most particleboards are produced from wood which may not be sustainable in the long term. Therefore, there is need of exploring alternative materials such as making particleboards from waste materials. This study investigated the mechanical properties of particleboard consisting of waste leather shavings and waste papers blended together by unsaturated polyester. A single-layered particleboards were manufactured using compression method. Different resin content (60%, 70%, 80%, and 90%) and leather/paper ratios (1:1, 1:3, 3:1) were used to determine the effects on the mechanical properties (internal bond, bending strength, compression and impact strength) of fabricated boards. From the results of this study, it was found that leather shavings and waste papers can be used as alternative raw materials for particleboard production and that mechanical properties were depended on the resin content and the blend ratio. Also, mechanical properties were reduced with resin content increment, except for impact strength and improved by high paper blend ratio

Rationale, aims and objectives: Epidemiologic data regarding chronic hepatitis B virus infections in Israel is limited as large population-based study have not been performed. This work aimed to evaluate the current characteristics of hepatitis B infection among Israeli adults, and to evaluate adherence to European Association for the Study of the Liver practice guidelines for antiviral treatment. Methods: Clinical and demographic data of HBsAg-positive patients registered in the Leumit-Health-Service database (one of the four major health maintenance organizations in Israel) between 2000-2019 were retrieved. Patients were compared according to eligibility to antiviral treatment and type of nucleos(t)ide analogue (NA) treatment. Results: In total, 1216 patients had documented HBsAg positivity (males 58.6%, mean age 40.2±14.2 years), 90.6% of whom were HBeAg negative. Antiviral therapy eligibility was met by 37% of patients, among whom 89% received antiviral therapy. Antiviral therapies include NA with a high barrier to resistance (HBR) (64.5%) (entecavir 36.3% and tenofovir 28.2%) and NA with a low barrier to resistance (LBR) (35.5%) (adefovir 1.7% and lamivudine 33.8%). Compared to patients who received LBR NA, patients receiving HBR NA had shorter treatment (68.7±50vs.161.5±42.6 months, p<0.0001) and follow-up duration (125±68vs.188±48 months, p<0.0001); at the end of follow-up, ALT levels and APRI score were higher among patients on LBR NA compared to patients on HBR NA. Conclusion: Most patients received antiviral treatment according to the international practice guidelines. However, one-third of them were treated with a less potent NA, probably due to their lower cost. These findings should encourage the optimization of HBV care and full compliance with the professional practice guidelines recommendations.

THAP9 is a transposable element-derived gene that encodes the THAP9 protein, which is homologous to the Drosophila P-element transposase (DmTNP) and can cut and paste DNA. However, the exact functional role of THAP9 is unknown. Here, we perform evolutionary analysis and extensive in silico characterization of THAP9, including predicting domains and putative post-translational modification sites. We predict previously unreported mammalian-specific post-translational modification sites that may play a role in the subcellular localization of THAP9. We also observe that although THAP9 has evolved under a strong pervasive purifying selection, yielding high conservation of THAP9, there are distinct class-specific conservation patterns of key functional residues in certain domains. Furthermore, investigation of THAP9 expression profiles in various cancer and matched normal datasets demonstrated underexpression and overexpression in testicular cancers and thymic epithelial tumors, respectively, thus suggesting a possible role of THAP9 in cancer.

Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment option for patients with acute lymphoblastic leukemia (ALL) very high-risk in first complete remission and relapsed disease that achieve remission patients. There is considerable variability in the regimens preparatory for conditioning patients to be transplanted. In this systematic review, we identify the impact of reduced-intensity regimen (RIC) or non-myeloablative (NMAC) on HSCT in pediatric ALL patients in terms of overall survival (OS) and disease-free survival (DFS) as reported in the scientific literature. Information was searched on nine databases, gray literature and bibliography cited in the selected articles, describing the results of HSCT in ALL in children between January 01, 2007, and June 30, 2021, with different preparative regimens. The literature search yielded an overall of 3841 articles; two articles were duplicates and rejected. This first selection included 363 articles, and 95 were selected for a complete reading. Finally, 16 articles that met the inclusion and exclusion criteria were included, which analyzed 2136 patients with ALL. RIC, NMAC, or reduced-intensity myeloablative regimen (RTMAC) was administered to 520 patients, demonstrating OS and DFS like other cohorts undergoing MAC. This article concludes the use of RIC, NMAC, or RTMAC is a reasonable option for those patients with ALL who require a transplant and who suffer from other comorbidities or have previous transplants, offering survival rates comparable with myeloablative regimens that, in combination with new alternatives such as immunotherapy, may become the best alternative.

Objective This study aimed to investigate correlation between 4‐hour delayed‐enhanced 3.0 Tesla (3T) 3D‐fluid‐attenuated inversion recovery (FLAIR) MR images and audio-vestibular function in idiopathic sudden sensorineural hearing loss. Setting Tertiary center Methods All patients underwent 4‐hour delayed‐enhanced 3D‐FLAIR MR imaging for identifying lesion-side laterality and enhanced labyrinth patterns. Audiologic and vestibular function tests were performed. Vestibular function test sum scores were additionally calculated by summing the scores on each test and defining normal as 0 and abnormal as 1. The hearing recovery was evaluated according to the American Academy of Otolaryngology-Head and Neck Surgery Criteria at 3 months after the end of treatment. Results Lesion-side laterality was identified in 31 (40.8%) of the 76 patients with ISSNHL and these patients had a lower hearing recovery rate (P<0.05). Furthermore, patients with a lower initial hearing threshold (dB), word recognition score, and lesion-side posterior semicircular canal gain displayed poorer hearing recovery (P<0.05). Initial hearing threshold and word recognition score did not change significantly as the extent of the enhancement in the labyrinth increased; however, the probability of being accompanied by vertigo and the total score on the vestibular function tests did increase (P<0.05). Conclusions Lesion-side laterality of the labyrinth in ISSNHL can be identified on 4-hour delayed-enhanced 3DFLAIR MR images. The extent of enhancement in the labyrinth is associated with clinical findings such as impaired audio-vestibular function, and also with the prognosis of ISSNHL. Keywords: Idiopathic sudden sensorineural hearing loss, 4-hour delayed 3D FLAIR MRI, Audiovestibular function, Prognosis. Level of Evidence; 4

Objective: To examine how the pandemic affected women with pelvic dysfunction. Design: A Survey Monkey™ questionnaire on how the pandemic and Covid-19 infection affected women’s pelvic problems, exercise, and weight. A free text box captured their comments. Setting: Online questionnaire worldwide. Sample: Six hundred and forty-seven women. Results: Bladder control 265 (41%), prolapse 240 (37%), pelvic pain 40 (6%), sexual dysfunction 27 (4%), faecal incontinence 19 (3%) and other 56 (9%) were respondents’ main pelvic problems. Symptoms were unchanged for 331 (51%), worse for 243 (38%), and improved for 60 (10%). Weight was gained by 290 (45%), unchanged by 243 (38%), and lost by 114 (17%). Exercise levels were unchanged, worse, or better in 33%. Difficulty accessing medical appointments and date for surgery were experienced by 235 (36.5%) and 38 (6%) women respectively. Sixty-six (10.3%) women reported covid-19 infection: the distribution of pelvic problems and changes through the pandemic, weight and exercise patterns, and difficulty either getting a date for surgery or accessing healthcare were similar to those not contracting infection. Sexual dysfunction was the main new or worsening problem, featuring 13 women (18%). Seventy women - 16 recently delivered, and 54 with a pre-existing pelvic problem commented. Five core themes were identified. Difficulty accessing healthcare review, mental health impact and physiotherapy services especially affected delivered women, while lifestyle alterations and conservative treatment tools were more prominent in women with a pre-existing problem. Conclusions: The pandemic left many women with pelvic dysfunction without services, and this survey captures their suffering.

There is concern about an increased risk of cardiovascular events in romosozumab users. This study evaluated the association between use of romosozumab and cardiovascular events using the Japanese Adverse Drug Event Report database. In total, 868 romosozumab users were identified. Disproportionality of cardiac events (reporting odds ratio [ROR]: 11.5, 95% confidence interval [CI]: 8.58–15.2; P < 0.01) and cerebrovascular events (ROR: 7.03, 95% CI: 5.46–8.93; P < 0.01) was observed. Cardiac events were significantly increased in patients with cardiac disease (odds ratio [OR]: 2.74, 95% CI: 1.37–5.49; P < 0.01), hypertension (OR: 1.97, 95% CI: 1.07–3.63; P = 0.03), and diabetes (OR: 2.36, 95% CI: 1.16–4.80; P = 0.02). Similar results were found regarding the risk factors for cerebrovascular events. This study suggests that comorbidities such as hypertension and diabetes may increase the risk of cardiovascular events in romosozumab users.

Voriconazole is the primary treatment for invasive pulmonary aspergillosis (IPA) and it has been used to treat patients colonized by Aspergillus spp. The pulmonary route could increase drug concentration in the biophase, reduce drug-drug interactions (DDI) and minimize adverse events (AE); however, there is scarce evidence about its use and there are no commercial voriconazole formulations for nebulization. The goal of this study is to characterize the compounded voriconazole solution for nebulization and describe its use in our center. This is a retrospective observational study including all patients treated with nebulized voriconazole to treat pulmonary fungal infections or colonizations. Voriconazole solution was prepared from commercial vials for intravenous administration. The pH and osmolarity of voriconazole solutions were adequate for nebulization, the dosage was 40 mg in adults and 10mg in the paediatric patient, administered every 12-24h. The median duration of treatment was 139 (26-911) days, there were no reported adverse effects related to voriconazole nebulization and the drug was not detected in plasma when used through the pulmonary route only. There were 3 cases of death, one case of voriconazole resistance, 3 cases of microbiological response, 2 cases of colonization without exacerbation and one case of successful prophylaxis. Voriconazole nebulization is well-tolerated and the drug is not absorbed into the systemic circulation. Further research is needed to assess voriconazole nebulization efficacy in specific clinical situations.

Universal filtered multi carrier (UFMC) system is considered to be the best choice for 5G waveform when compared with orthogonal frequency division multiplexing (OFDM), filtered OFDM (f-OFDM), filter bank multi carrier (FBMC) and generalized FDM (GFDM) in terms of spectral leakage, complexity and compatibility with 5G. The all multi carrier systems are suffers from high peak to average power ratio (PAPR) causes non linear functioning in receiver. In this paper, we proposed a Hirschman optimal transform (HOT) based pre-coding for reducing the PAPR in UFMC systems. Results reveals that HOT pre-coded UFMC promising less PAPR compared with discrete cosine transform (DCT), discrete Hartley transform (DHT) and discrete sine transform (DST) and discrete Fourier transform (DFT).

A three-parameter Omega probability distribution has been used recently to analyze the failure time data. In a practical situation, the Omega probability distribution was applied very effectively in modeling bathtub-shaped hazard curves. In this paper, the bivariate Omega (BOM) distribution whose marginal are Omega distributions is introduced. This new bivariate model is a Marshall-Olkin type and has natural interpretations for illustrated the shock and competing risks models. Some probabilistic properties of the bivariate Omega distribution are derived and studied. The dependence properties for bivariate Omega distribution are proposed using the Marshall-Olkin copula. Parameters estimators are investigated using the maximum likelihood method. Two data sets are illustrated to show the usefulness of the new model for fitting such data.

The chronic illness trajectory and its outcomes are well explained by the concept of illness identity; the extent to which ill individuals have integrated their diagnosed chronic illness into their identity or sense of self. The capacity to measure illness identity in people living with HIV (PLHIV) is still relatively unexplored. We explored the cross-cultural adaptation of a Belgian developed Illness Identity Questionnaire (IIQ) and validated the instrument using a sample of South African adults living with HIV. We followed a phased scale adaptation and validation process which included an investigation of conceptual, item and semantic equivalence. This was undertaken to assess relationship, meaning, acceptance and relevance of the illness identity construct, its latent factors and items in the South African context. For operational equivalence we evaluated whether the format, instructions and mode of administration of the IIQ could be maintained as in the original context. Lastly, we examined the psychometric properties of the IIQ. The concept of illness identity in PLHIV, was found relevant within this context. Five items from the original IIQ were excluded from the adapted IIQ due to either semantic insufficiency and/or inadequate measurement equivalence. The mode of administration of the IIQ was amended for the context. The original four factor 25-item model did not fit current data, however, a better contextualized, four-factor, 20-item model was identified and found valid in the current setting. The results showed adequate statistical fit; χ2/d.f. = 1.516, RMSEA = .076, SRMR = .0893, and CFI = .909. Convergent and discriminant validity were also tenable. The cross-cultural adaptation and validation of the IIQ was successful, resulting in the availability of an instrument capable of measuring illness identity in PLHIV in a high HIV prevalence and resource-constrained setting. This therefore addresses the paucity of information and expands on knowledge about illness identity.

Abstract: Objectives: Are LANC patients with carotid artery invasion are at risk of massive neck hemorrhage after radiotherapy? Design: This retrospective study aims to assess the efficacy of HT with CCRT +/-EGFR inhibitor in LANC patients invading carotid artery and risk of fatal bleeding. Settings: Otolaryngology Head and Neck Surgery department in our hospital in China . Participants: Of 130 LANC patients with carotid artery invasion admitted to our hospital between January 2012 and September 2019. Main outcome measures: The 5-year survival rate of three degrees of the carotid artery invasion (<180°, 180°≤IG<270°, ≥270°) . Univariate and Multivariate Cox regression analysis were used for survival correlation factors. Results: The incidence of fatal bleeding after radiotherapy was 2.3% (3/130). The primary site of the three cases were all the pharyngeal recess, with more than 270º carotid artery invasion. Patients with hemoglobin levels >110 g/L had a higher PFS, DMFS and OS than with that ≤110 g/L (P<0.05). Multivariate analysis showed that the EGFR inhibitor was an independent risk factor for PFS and DMFS, while the lowest hemoglobin level was an independent risk factor for OS. Conclusion: In LANC patients whose carotid artery invasion was <270º, HT combined with CCRT and EGFR inhibitor after induction chemotherapy had mild and tolerable side effects, better PFS and DMFS, with no massive hemorrhage. In patients ≥270º, diabetes with poor control or re-radiotherapy led to a higher risk of massive hemorrhage after radiotherapy.

Abstract Aims: SLC transporters are expressed in lungs and are essential membrane proteins responsible for the transport of wide range of chemotherapeutic drugs. Polymorphisms in SLC19A1, SLCO1B1, and SLCO1B3 gene in North Indian lung cancer patients are investigated. Methods: A total of 610 lung cancer patients undergoing platinum-based chemotherapy were recruited in the study. Polymorphisms of SLC19A1 (G80A), SLCO1B1 (A388G, T521C) and SLCO1B3 (A1683-5676G) in North Indian lung cancer patients were assessed and statistical analysis were carried out. Results: Our data revealed that patients harboring mutant genotype (AA) for SLC19A1 G80A polymorphism had higher MST as compared patients with wild type (GG) genotype (MST=9.33 versus 8.23). ADCC patients with mutant genotype (AA) showed better survival outcomes for SLC19A1 G80A (MST=9.4 versus 8.8, HR=0.6; p=0.04). In SCLC, SLC19A1 G80A polymorphism revealed increased survival in the patients harboring mutant genotype (AA) (MST=9.6 months versus 7.6 months, p=0.04). For SLCO1B3 polymorphism, patients administered with carboplatin/cisplatin and docetaxel showed inferior survival outcomes in subjects carrying heterozygous alleles (AG) (MST=2.9 months versus 9.6 months, p=0.006, HR=14.01). For anemia, SLCO1B1 T521C showed that patients with heterozygous genotype (TC) had a reduced risk of developing anemia (OR=0.44, 95% CI=0.20-0.96; p=0.04). Patients with SLCO1B1 A388G polymorphism harboring AG alleles was associated with a lower incidence of thrombocytopenia (OR=0.41, 95% CI=0.20-0.82; p=0.01). Patients with heterozygous (AG) genotype (OR=0.35, 95% CI=0.17-0.72; p=0.002) for A1683-5676G polymorphism showed lower incidence of nephrotoxicity. Conclusion: Genotyping of SLC polymorphism is crucial for predicting survival and toxicity in lung cancer patients undergoing platinum-based chemotherapy.

Background: “Rare cases of Burkitt leukemia/lymphoma (BL) exhibiting a precursor B-cell phenotype (termed herein pre-BLL) were admitted by WHO Classification of Hematopoetic and Lymphoid Tissue, recent evidence suggests that these neoplasms genetically and epigenetically resemble precursor B-cell leukemia/lymphoma (pB-acute lymphoblastic leukemia/lymphoblastic lymphoma (ALL)/LBL) rather than BL. The clinical features and treatment of childhood pre-BLL with C-myC rearrangement are poorly understood. Methods：The clinical features, treatment strategies and follow-up information of 9 cases with pre-BLL diagnosed by Shanghai Children’s Medical Center affiliated to Shanghai Jiao Tong University School of Medicine from 2011 to 2020 were retrospectively analyzed. Results: All the 9 cases were confirmed to be pre-BLL by flow cytometry and fluorescence in situ hybridization, morphological classification were L2/L3, immunophenotype was CD10, CD19 positive, CD20, TDT, CD34 selective expression, sIgM negative, Kappa and Lambda light chain negative. Most of the pre-BLL cases were accompanied by elevated lactate dehydrogenase (LDH), uric acid levels. 5 cases received intensive chemotherapy with overlapping regimen, and all achieved sustained remission except for 1 case relapse and death. Among the 4 cases who received low-intensity chemotherapy for acute lymphoblastic leukemia, 2 cases died due to early relapse of the disease. Conclusions: Pre-BLL cases are rare. and intensive chemotherapy treatment according to protocols for mature B-cell NHL. Currently, the treatment strategies are still controversial. Considering the small number of cases, multi-center clinical studies should be actively carried out to find a standard treatment plan.

Sequences similar to antithrombin-III in plants were retrieved from NCBI BLAST. Sequences showing homology more than 32% were shortlisted. Due to the non-availability of the crystal structures of the shortlisted sequences in the PDB database, models were generated using SWISS MODEL web server. The generated models were authenticated using SAVES web server. Best models for each sequence were selected and docked with thrombin using HawkDock web server. Out of 15 docked complexes, ALPP was shortlisted depending upon the highest binding affinity of -41.28 kcal/mol. Thrombin structure complexed with antithrombin-III like protein from Punica granatum (ALPP) was docked with TAME using AutoDock Vina to see if structure from ALPP affects the TAME binding. No interaction or binding is observed for TAME at 195Ser residue of thrombin. So after binding with ALPP, thrombin loses its affinity to bind with TAME at active site residue. MD simulation was performed for 20 ns to evaluate the flexibility and the stability of the docked complexes. The RMSD for the Thrombin-TAME complex was found to be 0.35nm whereas the RMSD of ALPP-Thrombin complex was found to be 0.4nm. Thus, it is very likely that the protein identified from Punica granatum may act as an inhibitor for thrombin.

Measles is an acute infectious disease which is highly contagious. This illness is caused by a negative sense, single-stranded RNA virus belonging to the Paramyxoviridae family. In spite of having a highly effective vaccine, measles is still a public health concern. In October 2019, Iran has achieved the status of measles elimination using effective vaccination strategies and surveillance system based on WHO recommendations. However, recent COVID-19 pandemic disrupted impeccable immunization services and altered health-seeking behaviors worldwide. Herein, we report a case of measles and influenza co-infection in a nine month-old infant from Bushehr province of Iran

Here, we present a case of a 36-year-old man with Neurofibromatosis Type 1 with spontaneous dialysis of ora serrata with no prior history of ocular trauma, possibly linked to abnormal cell-matrix formation in Neurofibromatosis Type 1.

Sanghuangporus baumii is a traditional medicinal fungus that contains triterpenoids with important pharmacological effects. However, the level of triterpenoids produced by S. baumii is far below the level demanded for application, and the pathway of triterpenoids biosynthesis is poorly understood. In this study, we established an Agrobacterium tumefaciens-mediated transformation system for the first time and transferred the key gene isopentenyl diphosphate isomerase ( IDI) involved in triterpenoids biosynthesis into S. baumii. The transcript level of IDI and the total triterpenoids content of the IDI transformant (IT) strain were significantly increased with respect to the wild-type (WT) strain. Then, we investigated the individual triterpenoids contained in S. baumii using metabolome and found 10 individual triterpenoids. All individual triterpenoids produced by IT strain showed the upward trend, were 1.76-10.03 times higher than those produced by the WT strain. Meanwhile, those individual triterpenoids showed significant positive correlation with the IDI gene. The findings provide valuable information about the biosynthetic pathway of triterpenoids and provide a strategy to cultivate S. baumii strains with high triterpenoids content.

The present study aimed to explore if bovine coronavirus nucleocapsid (BCoV N) impacts beta interferon (IFN-β) production in the host cells and to reveal further molecular mechanism of BCoV pathopoiesis. Human embryonic kidney (HEK) 293T cells were transientlly transfected with pCMV-Myc-BCoV-N recombinant plasmids, then infected with the vesicular stomatitis virus (VSV). Expression levels of IFN-β mRNA were detected using qPCR. The results determinated that pCMV-Myc-BCoV-N recombinant plasmids of 1347bp was successfully constructed and transcribed into HEK 293T cells. Western-blotting assay indicated that BCoV-N recombinant plasmids had excellent antigenicity. BCoV-N recombinant proteins inhibited dose-dependently IFN-β production mediated by Vesicular stomatitis virus (VSV) (P<0.01). Furthermore, MDA5, MAVS, TBK1 and IRF3 could promote transcription levels of IFN-β mRNA. But, BCoV-N proteins demoted IFN-β levels induced by MDA5, MAVS, TBK1 and IRF3. Expression levels of MDA5, MAVS, TBK1 and IRF3 mRNAs were reduced in retinoic acid-inducible gene I-like receptor (RLR) pathway. In conclusion, BCoV-N reduced IFN-β levels in RLR pathway of HEK 293T cells. BCoV-N protein inhibited IFN-β production and activation of RLRs signal pathway. Our findings demonstrated a new mechanism evolved by BCoV to inhibit type I IFN production and provided a solid scientific basis for revealing the pathogenesis of BCoV, which is beneficial for developing novel strategy of the diagnose and therapy of BCoV disease.

Reconstructing the phylogeny of the pine family (Pinaceae) has historically been problematic because analyses based on morphological characters and genetic analyses using small numbers of sequences have produced incongruent results. Such discrepancies may have resulted from continuous gene flow or genome mixing events among certain pine species. Here, we reconstructed a species-level tree of the Pinaceae using genome-wide data from seven pine species. A multi-locus analysis of SNPs from homologous fragments indicated that Pseudotsuga diverged from Pinus and Picea 167.26–149.19 million years ago. Analysis using the isolation-with-migration model identified significant signals of two-way gene flow between Pinus taeda and Pinus elliottii (P<0.001), while the isolation-with-initial-migration model suggested that introgression did not continue after this divergence. Gene flow has only ever occurred in the initial period of species divergence. Further analyses highlighted complex historical genome mixing and hybridization events over the evolution of the pine family. Thus, the divergence and radiation of the seven pines was a complex process accompanied by introgression and historical admixture.