Avian Tembusu virus infection effectively triggers host innate immune response through MDA5 and TLR3-dependent signaling pathways

Additional file 4 ATMUV infection causes significant up-regulation of TLR3 and MDA5. RT-PCR was performed to examine the mRNA expression of TLR3 and MDA5 in CEF (A), chickens (B) and 293T cells (C) at the indicated time after ATMUV infection, respectively

Long-Noncoding RNA Colorectal Neoplasia Differentially Expressed Gene as a Potential Target to Upregulate the Expression of IRX5 by miR-136-5P to Promote Oncogenic Properties in Hepatocellular Carcinoma

Background/Aims: The long-noncoding RNA colorectal neoplasia differentially expressed (CRNDE) gene was first found to be activated in colorectal neoplasia. Now, it also has been found to be upregulated in many other solid tumors. Whether CRNDE affects tumorigenesis remains unknown. Methods: We conducted bioinformatics, real-time polymerase chain reaction (PCR), Western blot analysis, cell proliferation assay, colony formation assay, wound healing assay, cell migration and invasion assays, RNA immunoprecipitation, and reporter vector construction and luciferase assays. Results: CRNDE was upregulated in hepatocellular carcinoma (HCC). The overexpression of CRNDE promoted HCC cellular proliferation, migration, and invasion in intro and in vivo, and acted as an oncogene in HCC progression. Furthermore, CRNDE impaired miR-136-5P expression in a RISC manner, and a reciprocal repression feedback loop was possible between CRNDE and miR-136-5P. We found that the neighboring mRNA of CRNDE was IRX5, and IRX5 increased the tumorigenicity of HCC cells. IRX5 was a potential downstream target gene of miR-136-5P. MiR-136 regulated IRX5 by interacting with its 3’UTR. In addition, miR-136-5P was involved in the CRNDE-regulated expression of IRX5. Conclusion: CRNDE acted as a tumor oncogene by exhibiting oncogenic properties of human HCC and revealed a novel CRNDE-miR-136-5P-IRX5 regulatory network in HCC. CRNDE may be considered to be a potential target for HCC therapies based on its ability to upregulate IRX5, and it deserves further investigation

Duck cGAS inhibits DNA and RNA virus replication by activating IFNs and antiviral ISGs

Cyclic GMP-AMP Synthase (cGAS) is a pivotal adaptor of the signaling pathways involving the pattern recognition receptors and plays an important role in apoptosis and immune regulation. The cGAS function in mammals has been investigated extensively; however, the function of duck cGAS (du-cGAS) in response to viral infections is still unclear. This study aimed to clone the mallard (Anas platyrhynchos) cGAS homolog to investigate the function of duck cGAS (du-cGAS) in host antiviral innate immunity. The results showed that the open reading frame (ORF) region of the du-cGAS gene was 1296 bp, encoding 432 amino acids (aa) and exhibiting similar functional domains with its chicken counterpart. Knockdown of the endogenous du-cGAS by specific sgRNA strongly increased the replication of DNA viruses, including duck adenovirus B2 (DAdV B2) and duck short beak and dwarfism syndrome virus (SBDSV). However, the knockout did not impair the replication of novel duck reovirus (NDRV), an RNA virus. Furthermore, the mRNA expressions of type I interferon (IFNs) and vital interferon-stimulated genes (ISGs) were remarkably reduced in the du-cGAS knockout DEF cell line. Inversely, du-cGAS overexpression greatly activated the transcription of IFN-α, IFN-β, and vital ISGs, and impaired the replication of DAdV B2, SBDSV, and NDRV in the DEF cell line. Importantly, we found that a deletion of 68 aa in the N terminus didn’t impair the antiviral function of du-cGAS. Overexpressing NTase Core, C-Domain (Mab21), or Zinc-Ribbon domain independently had no antiviral effects. Generally, these results reveal that du-cGAS is a vital component of the innate immune system of ducks, with a universal antiviral activity, and provides a useful strategy for the control of waterfowl viral diseases

An Open Invitation to Join the International Brugada Electrocardiographic Indices Registry

Background: The Brugada Electrocardiographic Indices Registry is a comprehensive data registry composed of patients with Brugada patterns on the electrocardiogram (ECG). The aim is to test the hypotheses that (i) ECG indices combining both depolarization and repolarization abnormalities can better predict spontaneous ventricular arrhythmias than existing ECG markers in Brugada syndrome and (ii) that serial ECG measurements will provide additional information for risk stratification, especially in asymptomatic patients. Methods: Patients with both Brugada pattern ECGs and Brugada syndrome are eligible for inclusion in this registry. Baseline characteristics and ECG variables reflecting depolarization and repolarization will be determined. The primary outcome is spontaneous ventricular tachycardia/ventricular fibrillation or sudden cardiac death. Secondary outcomes are inducible ventricular tachycardia/ventricular fibrillation and syncope. Results: As of November 15, 2019, 39 investigators from 32 cities in 18 countries had joined this registry. As of December 15, 2019, 1383 cases had been enrolled. Conclusions: The Brugada Electrocardiographic Indices Registry will evaluate the disease life course, risk factors, and prognosis in a large series of Brugada patients. It will therefore provide insights for improving risk stratification

Secular trends of health care resource utilization and costs between Brugada syndrome and congenital long QT syndrome: A territory‐wide study

Background Health care resource utilization (HCRU) and costs are important metrics of health care burden, but they have rarely been explored in the setting of cardiac ion channelopathies. Hypothesis This study tested the hypothesis that attendance-related HCRUs and costs differed between patients with Brugada syndrome (BrS) and congenital long QT syndrome (LQTS). Methods This was a retrospective cohort study of consecutive BrS and LQTS patients at public hospitals or clinics in Hong Kong, China. HCRUs and costs (in USD) for Accident and Emergency (A&E), inpatient, general outpatient and specialist outpatient attendances were analyzed between 2001 and 2019 at the cohort level. Comparisons were made using incidence rate ratios (IRRs [95% confidence intervals]). Results Over the 19-year period, 516 BrS (median age of initial presentation: 51 [interquartile range: 38−61] years, 92% male) and 134 LQTS (median age of initial presentation: 21 [9−44] years, 32% male) patients were included. Compared to LQTS patients, BrS patients had lower total costs (2 008 126 [2 007 622−2 008 629] vs. 2 343 864 [2 342 828−2 344 900]; IRR: 0.857 [0.855−0.858]), higher costs for A&E attendances (83 113 [83 048−83 177] vs. 70 604 [70 487−70 721]; IRR: 1.177 [1.165−1.189]) and general outpatient services (2,176 [2,166−2,187] vs. 921 [908−935]; IRR: 2.363 [2.187−2.552]), but lower costs for inpatient stay (1 391 624 [1 391 359−1 391 889] vs. 1 713 742 [1 713 166−1 714 319]; IRR: 0.812 [0.810−0.814]) and lower costs for specialist outpatient services (531 213 [531 049−531 376] vs. 558 597 [558268−558926]; IRR: 0.951 [0.947−0.9550]). Conclusions Overall, BrS patients consume 14% less health care resources compared to LQTS patients in terms of attendance costs. BrS patients require more A&E and general outpatient services, but less inpatient and specialist outpatient services than LQTS patients

Phylogeography of the South China Field Mouse (Apodemus draco) on the Southeastern Tibetan Plateau Reveals High Genetic Diversity and Glacial Refugia

The southeastern margin of the Tibetan Plateau (SEMTP) is a particularly interesting region due to its topographic complexity and unique geologic history, but phylogeographic studies that focus on this region are rare. In this study, we investigated the phylogeography of the South China field mouse, Apodemus draco, in order to assess the role of geologic and climatic events on the Tibetan Plateau in shaping its genetic structure. We sequenced mitochondrial cytochrome b (cyt b) sequences in 103 individuals from 47 sampling sites. In addition, 23 cyt b sequences were collected from GenBank for analyses. Phylogenetic, demographic and landscape genetic methods were conducted. Seventy-six cyt b haplotypes were found and the genetic diversity was extremely high (π = 0.0368; h = 0.989). Five major evolutionary clades, based on geographic locations, were identified. Demographic analyses implied subclade 1A and subclade 1B experienced population expansions at about 0.052-0.013 Mya and 0.014-0.004 Mya, respectively. The divergence time analysis showed that the split between clade 1 and clade 2 occurred 0.26 Mya, which fell into the extensive glacial period (EGP, 0.5-0.17 Mya). The divergence times of other main clades (2.20-0.55 Mya) were congruent with the periods of the Qingzang Movement (3.6-1.7 Mya) and the Kun-Huang Movement (1.2-0.6 Mya), which were known as the most intense uplift events in the Tibetan Plateau. Our study supported the hypothesis that the SEMTP was a large late Pleistocene refugium, and further inferred that the Gongga Mountain Region and Hongya County were glacial refugia for A. draco in clade 1. We hypothesize that the evolutionary history of A. draco in the SEMTP primarily occurred in two stages. First, an initial divergence would have been shaped by uplift events of the Tibetan Plateau. Then, major glaciations in the Pleistocene added complexity to its demographic history and genetic structure

Conserved and Diversified Mechanism of Autophagy between Plants and Animals upon Various Stresses

Autophagy is a highly conserved degradation mechanism in eukaryotes, executing the breakdown of unwanted cell components and subsequent recycling of cellular material for stress relief through vacuole-dependence in plants and yeast while it is lysosome-dependent in animal manner. Upon stress, different types of autophagy are stimulated to operate certain biological processes by employing specific selective autophagy receptors (SARs), which hijack the cargo proteins or organelles to the autophagy machinery for subsequent destruction in the vacuole/lysosome. Despite recent advances in autophagy, the conserved and diversified mechanism of autophagy in response to various stresses between plants and animals still remain a mystery. In this review, we intend to summarize and discuss the characterization of the SARs and their corresponding processes, expectantly advancing the scope and perspective of the evolutionary fate of autophagy between plants and animals

Harmony but Not Uniformity: Role of Strigolactone in Plants

Strigolactones (SLs) represent an important new plant hormone class marked by their multifunctional roles in plants and rhizosphere interactions, which stimulate hyphal branching in arbuscular mycorrhizal fungi (AMF) and seed germination of root parasitic plants. SLs have been broadly implicated in regulating root growth, shoot architecture, leaf senescence, nodulation, and legume–symbionts interaction, as well as a response to various external stimuli, such as abiotic and biotic stresses. These functional properties of SLs enable the genetic engineering of crop plants to improve crop yield and productivity. In this review, the conservation and divergence of SL pathways and its biological processes in multiple plant species have been extensively discussed with a particular emphasis on its interactions with other different phytohormones. These interactions may shed further light on the regulatory networks underlying plant growth, development, and stress responses, ultimately providing certain strategies for promoting crop yield and productivity with the challenges of global climate and environmental changes