Demographic, Virological Characteristics and Prognosis of Asymptomatic COVID-19 Patients in South China.

BACKGROUND: Asymptomatic transmission is a major concern for SARS-CoV-2 community spread; however, little information is available on demographic, virological characteristics and prognosis of asymptomatic cases. METHODS: All COVID-19 patients hospitalized in Guangdong Province from September 1, 2020 to February 28, 2021, were included and were divided into asymptomatic and symptomaticgroup. The source country of all patients, clinical laboratory test results, the genotype of virus and the time of SARS-CoV-2 RNA turning negative or hospitalization were confirmed. RESULTS: Total 233 patients from 57 different countries or regions were included, with 83 (35.6%) asymptomatic and 150 (64.4%) symptomatic patients. Asymptomatic cases were younger (P = 0.019), lower rate in comorbidities (P = 0.021) such as hypertension (P = 0.083) and chronic liver disease (P = 0.045), lower PCT (P = 0.021), DDI (P < 0.001) and ALT (P = 0.029), but higher WBC count (P = 0.002) and lymphocyte (P = 0.011) than symptomatic patients. As for SARS-CoV-2 subtypes, patients infected with B.1.1 (53.8%), B.1.351 (81.8%) and B.1.524 (60%) are mainly asymptomatic, while infected with B, B.1, B.1.1.63, B.1.1.7, B.1.36, B.1.36.1, B.1.36.16, B.1.5 and B.6 were inclined to be symptomatic. Patients infected with variant B.1.351 and B.1.524 spent longer time in SARS-CoV-2 RNA turn negative (26 days, P = 0.085; 41 days, P = 0.007) and hospitalization (28 days, P = 0.085; 43 days, P = 0.004). CONCLUSIONS: The asymptomatic cases are prone to develop in patients with younger age, less comorbidities andinfected with B.1.1 and B.1.524 variants. More attention should be paid for lineage B.1.524 because it can significantly prolong the SARS-CoV-2 RNA negative conversion time and hospitalization in infected cases.

Urinary Trypsin Inhibitor Protects Tight Junctions of Septic Pulmonary Capillary Endothelial Cells by Regulating the Functions of Macrophages.

BACKGROUND: Our previous study found that urinary trypsin inhibitor (ulinastatin, UTI) protected tight junctions (TJs) of lung endothelia via TNF-α inhibition, thereby alleviating pulmonary capillary permeability in septic rats. As the activated macrophage is the main source of TNF-α in sepsis, we speculate that UTI may exert the above effects by regulating the functions of macrophages. METHODS: Bone-marrow derived macrophages (BMDM) were divided into control, lipopolysaccharide (LPS), UTI+LPS and UTI groups. TNF-α, TGF-ß, IL-10, CD86, CD206 and MCP-1 expression were assessed by Western blot. The phagocytosis and migration of BMDM were detected. Pulmonary microvascular endothelial cells (PMVECs) were cultured with the conditioned medium (CM) from each group of BMDM above. Sprague-Dawley rats were divided into sham, cecal ligation and puncture (CLP), and UTI+CLP groups. Western blot and immunofluorescence were used to detected zonula occludens-1 (ZO-1), occludin and claudin-5 expression in PMVECs, as well as TNF-α, TGF-ß, iNOS, CD86 and CD206 expression in lungs. Pulmonary capillary permeability was assessed by extravasated Evans blue, lung injury score (LIS), wet-to-dry weight ratio and electron microscope. RESULTS: TNF-α and CD86 expression were increased in LPS-treated BMDM, but were reversed by UTI pretreatment. TGF-ß, IL-10 and CD206 expression were the opposite. UTI markedly decreased phagocytosis and migration of LPS-treated BMDM. ZO-1, occludin and claudin-5 expression were markedly decreased in PMVECs of the CM-LPS group, but significantly increased in the CM-UTI+LPS group. TNF-α, iNOS and CD86 expression were increased in the lungs of CLP-rats but decreased with UTI pretreatment, while TGF-ß and CD206 expression were the opposite. UTI markedly ameliorated the lung EB leakage, improved LIS, reduced the wet-to-dry ratio and revised the damaged TJs of PMVECs in CLP-rats. CONCLUSION: UTI effectively inhibits the conversion of M1 macrophage but increases M2, reduces the phagocytosis and migration, which helps to protect endothelia TJs and reduce pulmonary capillary permeability during sepsis.

bHLH13 Regulates Jasmonate-Mediated Defense Responses and Growth.

Jasmonates (JAs) regulate plant growth and defense responses. On perception of bioactive JAs, the JA receptor CORONATINE INSENSITIVE1 (COI1) recruits JA ZIM-domain (JAZ) proteins for degradation, and JAZ-targeted transcription factors are released to regulate JA responses. The subgroup IIId bHLH transcriptional factors, including bHLH17, bHLH13, bHLH3, and bHLH14, interact with JAZs and repress JA responses. In this study, we show that IIId bHLH factors form dimers via the C-terminus in yeast. N-terminus of bHLH13 is essential for its transcriptional repression function. bHLH13 overexpression inhibits Arabidopsis resistance to the necrotrophic fungi Botrytis cinerea and defense against the insect Spodoptera exigua. COI1 mutation disrupts the oversensitivity of the quadruple mutant bhlh3 bhlh13 bhlh14 bhlh17 in various JA responses, including anthocyanin accumulation, root growth inhibition, and defense against B cinerea and S exigua. Disruption of the TTG1/bHLH/MYB complex blocks anthocyanin accumulation of bhlh3 bhlh13 bhlh14 bhlh17, whereas abolishment of MYC2 attenuates JA-inhibitory root growth of bhlh3 bhlh13 bhlh14 bhlh17. These results genetically demonstrate that IIId bHLH factors function downstream of COI1 to inhibit distinctive JA responses via antagonizing different transcriptional activators.

Arabidopsis ENOR3 regulates RNAi-mediated antiviral defense.

Viruses can infect host plants to cause severe diseases and substantial agricultural loss, while plants have evolved RNA interference (RNAi) strategy to defend against viral infection. Despite enormous efforts, only a few host proteins in RNAi pathway were shown to mediate antiviral defense, including RNA-dependent RNA polymerase 1 (RDR1), RDR6, DICER-LIKE 2 (DCL2) and DCL4. In this study, we carried out a genetic screen for antiviral factors of RNAi pathway in Arabidopsis rdr6 background via inoculation with a 2b-deficient Cucumber Mosaic Virus (CMV-Δ2b). We identified a mutant susceptible to CMV-Δ2b, referred to as enhancer of rdr6 (enor) 3-1 rdr6, and found that ENOR3 encodes a functionally unknown protein with high homology to the mammalian Non Imprinted in Prader-Willi/Angelman (NIPA) magnesium transporters. ENOR3 inhibits accumulation of CMV-Δ2b and acts additively with RDR1, RDR6, DCL2 and DCL4 in antiviral defense. These results uncover that ENOR3 is a key component in antiviral RNAi pathway, and provide new insights into antiviral immunity.

TNF-α-inducing protein of Helicobacter pylori induces epithelial-mesenchymal transition (EMT) in gastric cancer cells through activation of IL-6/STAT3 signaling pathway.

Tumor necrosis factor (TNF)-α-inducing protein (Tipα) is a newly identified carcinogenic factor secreted by Helicobacter pylori (H. pylori). Although it has been proved that Tipα is a strong inducer of epithelial-mesenchymal transition (EMT), a crucial process of migration, the exact molecular mechanism is unknown. Current evidence indicates that the oncogenic transcription factor signal transducers and activators of transcription 3 (STAT3) is inappropriately activated in multiple malignancies, including gastric cancer. In this study, we showed that Tipα significantly down-regulated the expression of EMT-related markers E-cadherin as well as up-regulated N-cadherin and vimentin in SGC7901 cells, with typical morphological changes of EMT. Tipα also promoted proliferation and migration of SGC7901 cells. Furthermore, Tipα activated interleukin-6 (IL-6)/STAT3 signaling pathway in SGC7901 cells. The effects of Tipα treatment observed was abolished when we block IL-6/STAT3 signaling pathway. Altogether, our data demonstrated that Tipα may accelerate tumor aggressiveness in gastric cancer by promoting EMT through activation of IL-6/STAT3 pathway.