Stress granules (SGs) contain stalled messenger ribonucleoprotein complexes and are related to the regulation of mRNA translation. Picornavirus infection can interfere with the formation of SGs. However, the detailed molecular mechanisms and functions of picornavirus-mediated regulation of SG formation are not clear. Here, we found that the 2A protease of a picornavirus, EV71, induced atypical stress granule (aSG), but not typical stress granule (tSG), formation via cleavage of eIF4GI. Furthermore, 2A was required and sufficient to inhibit tSGs induced by EV71 infection, sodium arsenite, or heat shock. Infection of 2A protease activity-inactivated recombinant EV71 (EV71-2AC110S) failed to induce aSG formation and only induced tSG formation, which is PKR and eIF2α phosphorylation-dependent. By using a Renilla luciferase mRNA reporter system and RNA fluorescence in situ hybridization assay, we found that EV71-induced aSGs were beneficial to viral translation through sequestering only cellular mRNAs, but not viral mRNAs. In addition, we found that the 2A protease of other picornaviruses such as poliovirus and coxsackievirus also induced aSG formation and blocked tSG formation. Taken together, our results demonstrate that, on one hand, EV71 infection induces tSG formation via the PKR-eIF2α pathway, and on the other hand, 2A, but not 3C, blocks tSG formation. Instead, 2A induces aSG formation by cleaving eIF4GI to sequester cellular mRNA but release viral mRNA, thereby facilitating viral translation.

A potent unpleasant aroma presenting a pickle-like off-odor in Moutai-aroma type Baijiu was studied by comparative aroma extract dilution analysis (AEDA). Two Moutai-aroma type Baijiu samples, one having no off-odor (A) and the other one presenting pickle-like off-odor (B), were selected for chemical analysis and sensory evaluation. The aroma compounds were isolated by headspace solid-phase microextraction and liquid–liquid extraction. AEDA, quantitative analysis, and odor activity value calculation were performed in both the A and B samples. The main differences between the two samples were obtained for 12 compounds, presenting significantly higher concentrations in the off-odor sample. A total of 30 Moutai-aroma type Baijiu samples having different intensities of pickle-like sensory defect were analyzed to confirm the differences. An aroma addition test indicated that the 12 compounds with higher concentrations contributed to the pickle-like off-odor when spiked into sample A. Finally, a triangle test involving omission of the aroma compounds from the spiked A sample proved that 2-methyl-3-furanthiol, methional, methyl 2-methyl-3-furyl disulfide, dimethyl trisulfide, 2-furfurylthiol, methanethiol, dimethyl disulfide, and bis­(2-methyl-3-furyl)­disulfide with higher concentrations were generally responsible for the pickle-like off-odor in Moutai-aroma type Baijiu.

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BackgroundElevated plasma fibrinogen (Fbg) levels contribute to tumor progression and metastasis; however, limited research on Fbg in small cell lung cancer (SCLC) has been conducted. This study evaluated the prognostic value of Fbg levels in patients with SCLC.MethodsData on plasma Fbg level, clinical features, and overall survival were retrospectively collected. Kaplan–Meier estimates and log‐rank tests were used to analyze the relationship between Fbg level and survival. Multivariate analyses were performed to determine independent prognostic factors. Subgroup analyses were performed based on extensive/limited disease and Eastern Cooperative Oncology Group status.ResultsA total of 120 patients with SCLC were included. The one, three, and five‐year survival rates for the entire cohort were 48.3%, 9.2%, and 1.7%, respectively. Univariate analyses revealed that age, alcohol use, clinical stage, pleural effusion, Eastern Cooperative Oncology Group grade, and Fbg and lactate dehydrogenase levels were associated with survival (P < 0.05). The median survival time for patients with high Fbg levels (> 400 mg/dL) was shorter than for those with low Fbg levels (8 vs. 14 months; P = 0.013). Furthermore, multivariate analysis revealed that Fbg was negatively and independently associated with SCLC prognosis (hazard ratio 1.505, 95% confidence interval 1.018–2.226; P = 0.041). Higher Fbg levels were associated with shorter survival in the extensive disease subgroup (7 vs. 12 months; P = 0.004).ConclusionsElevated plasma Fbg was an independent factor associated with poor outcomes in SCLC patients and could serve as a prognostic biomarker.