Comparison analysis of microRNAs in response to EV71 and CA16 infection in human bronchial epithelial cells by high-throughput sequencing to reveal differential infective mechanisms

AbstractHand, foot, and mouth disease (HFMD) mainly caused by Enterovirus 71 (EV71) and coxsackievirus A16 (CA16) infections which presented significantly different clinical manifestations. Nevertheless, the factors underlying these differences remain unclear. Recently, the functions of microRNAs (miRNAs) in pathogen-host interactions have been highlighted. Here, we performed comprehensive miRNA profiling in EV71- and CA16-infected human bronchial epithelial (16HBE) cells at multiple time points using high-throughput sequencing. The results showed that 154 known and 47 novel miRNAs exhibited remarkable differences in expression. Of these, 65 miRNAs, including 58 known and 7 novel miRNAs, presented opposite trends in EV71- and CA16-infected samples. Subsequently, we mainly focused on the 56 known differentially expressed miRNAs by further screening for targets prediction. GO and pathway analysis of these targets demonstrated that 18 biological processes, 7 molecular functions, 1 cellular component and 123 pathways were enriched. Among these pathways, Cadherin signalling pathway, Wnt signalling pathway and angiogenesis showed significant alterations. The regulatory networks of these miRNAs with predicted targets, GOs, pathways and transcription factors were determined, which suggested that miRNAs displayed intricate regulatory mechanisms during the infection phase. Consequently, we specifically analysed the hierarchical GO categories of the predicted targets involved in adhesion. The results indicated that the distinct changes induced by EV71 and CA16 infection may be partly linked to airway epithelial barrier function. Taken together, our data provide useful insights that help elucidate the different host-pathogen interactions following EV71 and CA16 infection and might offer novel therapeutic targets for these infections

Network Modeling Identifies Molecular Functions Targeted by miR-204 to Suppress Head and Neck Tumor Metastasis

Due to the large number of putative microRNA gene targets predicted by sequence-alignment databases and the relative low accuracy of such predictions which are conducted independently of biological context by design, systematic experimental identification and validation of every functional microRNA target is currently challenging. Consequently, biological studies have yet to identify, on a genome scale, key regulatory networks perturbed by altered microRNA functions in the context of cancer. In this report, we demonstrate for the first time how phenotypic knowledge of inheritable cancer traits and of risk factor loci can be utilized jointly with gene expression analysis to efficiently prioritize deregulated microRNAs for biological characterization. Using this approach we characterize miR-204 as a tumor suppressor microRNA and uncover previously unknown connections between microRNA regulation, network topology, and expression dynamics. Specifically, we validate 18 gene targets of miR-204 that show elevated mRNA expression and are enriched in biological processes associated with tumor progression in squamous cell carcinoma of the head and neck (HNSCC). We further demonstrate the enrichment of bottleneckness, a key molecular network topology, among miR-204 gene targets. Restoration of miR-204 function in HNSCC cell lines inhibits the expression of its functionally related gene targets, leads to the reduced adhesion, migration and invasion in vitro and attenuates experimental lung metastasis in vivo. As importantly, our investigation also provides experimental evidence linking the function of microRNAs that are located in the cancer-associated genomic regions (CAGRs) to the observed predisposition to human cancers. Specifically, we show miR-204 may serve as a tumor suppressor gene at the 9q21.1–22.3 CAGR locus, a well established risk factor locus in head and neck cancers for which tumor suppressor genes have not been identified. This new strategy that integrates expression profiling, genetics and novel computational biology approaches provides for improved efficiency in characterization and modeling of microRNA functions in cancer as compared to the state of art and is applicable to the investigation of microRNA functions in other biological processes and diseases

Surveys of Drosophila suzukii (Diptera: Drosophilidae) and Its Host Fruits and Associated Parasitoids in Northeastern China

Spotted-wing drosophila, Drosophila suzukii (Matsumura), is a worldwide quarantine pest that is currently undergoing a rapid range expansion in the Americas, Europe, and parts of Africa. It feeds and breeds on soft-skinned fruits such as raspberries, blueberries, and cherries, and can cause significant economic losses to fruit production. This study investigated the occurrence of D. suzukii and its wild host fruits and parasitoids in Liaoning, Northeast China for the first time. Sentinel traps were used to monitor D. suzukii adults, and suspected fruits were collected weekly in four different locations (Wafangdian, Faku, Fengcheng, and Shenyang). The results showed that D. suzukii were distributed in the sweet soft-skinned fruit-production areas of Liaoning, and raspberry was the most infested fruit. During the field survey, four species of wild berries from non-crop habitats were found infested by D. suzukii, and two species of parasitoids (Leptopilina japonica and Asobara japonica) were collected. D. suzukii adult-population dynamics throughout the survey period (June to October) were similar in different survey locations; adult fly populations increased and peaked in August, and then declined until the fly was no longer detectable in October

Larval Instars and Adult Flight Period of <i>Monochamus saltuarius</i> (Coleoptera: Cerambycidae)

Monochamus saltuarius is a vector of Bursaphelenchus xylophilus in Japan, South Korea, and the middle temperate zone of China. However, there are only a few reports on this species in China, and its biological characteristics are still unclear. In this study, we aimed to elucidate the larval development and adult flight period of M. saltuarius to provide a theoretical basis for the effective control of pine wilt disease in the middle temperate zone of China. Seven morphological variables of larvae were measured to determine the number of larval instars, and the adult specimens of M. saltuarius were collected from traps in forests to study the flight period of adults in Fushun, Liaoning, the epidemic center of pine wilt disease in the middle temperate zone of China. The results revealed that the full larval period of M. saltuarius was 279.6 d, and the larvae had five instar stages, with an average duration of 7.4, 14.3, 49.8, 83.6, and 124.5 d, respectively. Additionally, 78.4% of the overwintering larvae were fourth instar, and 21.6% were fifth instar larvae. We also found that the adults began to emerge from early May to late June, and the period was from early May to mid-August in the forest. During the investigations period from 2018 to 2020, the total number of adults captured was minimal at 744, and precipitation was highest at 291.54 mm in 2019. We characterized the larval instars and adult flight period of M. saltuarius, which is a prerequisite for developing appropriate management strategies. The results of this study will provide an important reference for the formulation of strategies to control M. saltuarius and pine wilt disease

Recognition Site Modifiable Macrocycle: Synthesis, Functional Group Variation and Structural Inspection

Traditional macrocyclic molecules encode recognition sites in their structural backbones, which limits the variation of the recognition sites and thus, would restrict the adjustment of recognition properties. Here, we report a new oligoamide-based macrocycle capable of varying the recognition functional groups by post-synthesis modification on its structural backbone. Through six steps of common reactions, the parent macrocycle (9) can be produced in gram scale with an overall yield of 31%. The post-synthesis modification of 9 to vary the recognition sites are demonstrated by producing four different macrocycles (10&ndash;13) with distinct functional groups, 2-methoxyethoxyl (10), hydroxyl (11), carboxyl (12) and amide (13), respectively. The 1H NMR study suggests that the structure of these macrocycles is consistent with our design, i.e., forming hydrogen bonding network at both rims of the macrocyclic backbone. The 1H-1H NOESY NMR study indicates the recognition functional groups are located inside the cavity of macrocycles. At last, a preliminary molecular recognition study shows 10 can recognize n-octyl-&beta;-D-glucopyranoside (14) in chloroform

Recognition Site Modifiable Macrocycle: Synthesis, Functional Group Variation and Structural Inspection

Traditional macrocyclic molecules encode recognition sites in their structural backbones, which limits the variation of the recognition sites and thus, would restrict the adjustment of recognition properties. Here, we report a new oligoamide-based macrocycle capable of varying the recognition functional groups by post-synthesis modification on its structural backbone. Through six steps of common reactions, the parent macrocycle (9) can be produced in gram scale with an overall yield of 31%. The post-synthesis modification of 9 to vary the recognition sites are demonstrated by producing four different macrocycles (10–13) with distinct functional groups, 2-methoxyethoxyl (10), hydroxyl (11), carboxyl (12) and amide (13), respectively. The 1H NMR study suggests that the structure of these macrocycles is consistent with our design, i.e., forming hydrogen bonding network at both rims of the macrocyclic backbone. The 1H-1H NOESY NMR study indicates the recognition functional groups are located inside the cavity of macrocycles. At last, a preliminary molecular recognition study shows 10 can recognize n-octyl-β-D-glucopyranoside (14) in chloroform

Transient Pressure Performance Analysis of Hydraulically Fractured Horizontal Well in Tight Oil Reservoir

Utilizing the discrete fracture model (DFM), a transient flow model is established for fractured horizontal wells in tight oil reservoirs, accounting for threshold pressure gradient (TPG), stress sensitivity effect, hydraulic fracture parameters, and fracture distribution pattern. This model is solved using the finite-volume method (FVM), and an important sensitivity analysis is conducted. The findings reveal that the models incorporated by the threshold pressure gradient result in an upward trend in the pressure-derivative curve. As the threshold pressure gradient increases, this upward trend becomes more pronounced, rendering the distinction between flow regimes more challenging. The stress sensitivity effect predominantly impacts the pressure-derivative curve during the later flow period. Additionally, as the fracture half-length increases, the pressure performance of both fracture radial flow and formation radial flow becomes more difficult. Fracture conductivity has a significant influence during the early flow period, facilitating the identification of flow regimes with the trend of increasing fracture conductivity