In order to discover novel potential antifungal agents, a series of 6-substituted 3-butylphthalide derivatives were designed, synthesized and evaluated for their antifungal activities against nine phytopathogenic fungi. Preliminary bioassay tests showed that five 3-butylphthalide derivatives exhibited more potent antifungal activities than hymexazol at the concentration of 50 μg/mL. Especially, 3-butyl-6-nitro-2-benzofuran-1(3H)-one and 3-butyl-6-hydroxy-5-nitro-2-benzofuran-1(3H)-one had significant fungicidal activity against some phytopathogenic fungi. The EC 50 of 3-butyl-6-nitro-2-benzofuran-1(3H)-one against FS, FO and FG were 6.6, 9.6 and 16.0 μg/mL, respectively. The EC 50 of 3-butyl-6-hydroxy-5-nitro-2-benzofuran-1(3H)-one against BC, PO, VM, SS and AS were 6.3, 5.9, 10.0, 4.5 and 8.4 μg/mL, respectively. The preliminary structure-activity relationships (SARs) of all target compounds were also investigated.

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the recent global COVID-19 outbreak, which led to a public health emergency. Entry of SARS-CoV-2 into human cells is dependent on the SARS-CoV receptor, angiotensin converting enzyme 2 (ACE2) receptor, and cathepsin. Cathepsin degrades the spike protein (S protein), which results in the entry of viral nucleic acid into the human host cell. Methods We explored the susceptibility of the central nervous system (CNS) to SARS-CoV-2 infection using single-cell transcriptome analysis of glioblastoma. Results The results showed that ACE2 expression is relatively high in endothelial cells (ECs), bone marrow mesenchymal stem cells (BMSCs), and neural precursor cells (NPCs). Cathepsin B (Cat B) and cathepsin (Cat L) were also strongly expressed in various cell clusters within the glioblastoma microenvironment. Immunofluorescence staining of glioma and normal brain tissue chips further confirmed that ACE2 expression co-localized with CD31, CD73, and nestin, which confirmed the susceptibility to SARS-CoV-2 of nervous system cells, including ECs, BMSCs, and NPCs, from clinical specimens. Conclusions These findings reveal the mechanism of SARS-CoV-2 neural invasion and suggest that special attention should be paid to SARS-CoV-2–infected patients with neural symptoms, especially those who suffered a glioma.

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Abstract. Acute-on-chronic liver failure (ACLF) is a syndrome with a high rate of short-term mortality, and clinically it is important to identify patients at high risk of mortality. The present study evaluated the value of osteopontin (OPN) in the prediction of 90-day mortality in patients with ACLF. A total of 54 patients with HBV-associated ACLF were enrolled, and serum OPN levels were determined in a prospective, observational study design. Survival analysis was performed using Kaplan-Meier curves, and multivariate Cox proportional hazards regression was used to analyze independent risk factors of mortality. Serum OPN was significantly higher in HBV-ACLF patients compared with patients with chronic hepatitis B and healthy controls (both P<0.01), and furthermore, was higher in those patients who succumbed to HBV-ACLF compared with surviving patients (P<0.05). OPN level positively correlated with total bilirubin (r=0.554, P<0.001), Model for End-Stage Liver Disease (MELD) score (r=0.234, P=0.038), MELD-Na score (r=0.379, P=0.005) and monocyte count (r=0.282, P=0.039), and OPN was an independent risk factor for 90-day mortality in ACLF (P=0.021, odds ratio=1.104, 95% confidence interval: 1.003-1.116). Furthermore, ACLF patients were stratified into three groups according to serum OPN levels (low mortality risk: <6,135 ng/ml; intermediate risk: 6,135-9,043 ng/ml; and high risk: >9,043 ng/ml), for which the 90-day mortality rates were 27.78 (5/18), 52.94 (9/17) and 73.68% (14/19), respectively, and those in the high risk had a poorer prognosis compared with the low risk group (P=0.009). In conclusion, serum OPN may be an independent risk factor associated with HBV-ACLF prognosis.

To investigate the roles of tripartite motif containing 52 (TRIM52) in human hepatic fibrosis in vitro, human hepatic stellate cell line LX‐2 cells were transfected with hepatitis B virus (HBV) replicon to establish HBV‐induced fibrosis in LX‐2 cells, and then treated with small interfering RNA‐mediated knockdown of TRIM52 (siTRIM52). LX‐2 cells without HBV replicon transfection were treated with lentiviruses‐mediated overexpression of TRIM52 and phosphatase magnesium dependent 1A (PPM1A). Fibrosis response of LX‐2 cells were assessed by the production of hydroxyproline (Hyp) and collagen I/III, as well as protein levels of α‐smooth muscle actin (α‐SMA). PPM1A and phosphorylated (p)‐Smad2/3 were measured to assess the mechanism. The correlation between TRIM52 and PPM1A was determined using co‐immunoprecipitation, and whether and how TRIM52 regulated the degradation of PPM1A were determined by ubiquitination assay. Our data confirmed HBV‐induced fibrogenesis of LX‐2 cells, as evidenced by significant increase in Hyp and collagen I/III and α‐SMA, which was associated with reduction of PPM1A and elevation of transforming growth factor‐β (TGF‐β), p‐Smad2/3, and p‐Smad3L. However, those changes induced by HBV were significantly attenuated with additional siTRIM52 treatment. Similar to HBV, overexpression of TRIM52 exerted promoted effect in the fibrosis of LX‐2 cells. Interestingly, TRIM52 induced the fibrogenesis of LX‐2 cells and the activation of TGF‐β/Smad pathway were significantly reversed by PPM1A overexpression. Furthermore, our data confirmed TRIM52 as a deubiquitinase that influenced the accumulation of PPM1A protein, and subsequently regulated the fibrogenesis of LX‐2 cells. TRIM52 was a fibrosis promoter in hepatic fibrosis in vitro, likely through PPM1A‐mediated TGF‐β/Smad pathway.