An IgM-like inhalable ACE2 fusion protein broadly neutralizes SARS-CoV-2 variants.

Many of the currently available COVID-19 vaccines and therapeutics are not effective against newly emerged SARS-CoV-2 variants. Here, we developed the metallo-enzyme domain of angiotensin converting enzyme 2 (ACE2)-the cellular receptor of SARS-CoV-2-into an IgM-like inhalable molecule (HH-120). HH-120 binds to the SARS-CoV-2 Spike (S) protein with high avidity and confers potent and broad-spectrum neutralization activity against all known SARS-CoV-2 variants of concern. HH-120 was developed as an inhaled formulation that achieves appropriate aerodynamic properties for rodent and monkey respiratory system delivery, and we found that early administration of HH-120 by aerosol inhalation significantly reduced viral loads and lung pathology scores in male golden Syrian hamsters infected by the SARS-CoV-2 ancestral strain (GDPCC-nCoV27) and the Delta variant. Our study presents a meaningful advancement in the inhalation delivery of large biologics like HH-120 (molecular weight (MW) ~ 1000 kDa) and demonstrates that HH-120 can serve as an efficacious, safe, and convenient agent against SARS-CoV-2 variants. Finally, given the known role of ACE2 in viral reception, it is conceivable that HH-120 has the potential to be efficacious against additional emergent coronaviruses.

Altered staining patterns and expression level of Engrailed-2 in benign prostatic hyperplasia and prostate Cancer predict prostatic disease progression.

BACKGROUND: Prostate cancer (PC), a common malignant tumor, is the second-leading cause of cancer death among American men. Its successful treatment greatly relies on the early diagnose. Engrailed-2 (EN2) has been confirmed being existed with a high level in the urine of PC patients. In this study, to explore the application of EN2 in PC, we detected the immunohistochemical staining difference and EN2 expression level between benign prostatic hyperplasia (BPH) and PC. METHODS: We developed a monoclonal antibody against the helix 3 in EN2 and confirmed its specificity with Western blotting (WB) and immunofluorescence detecting the subcellular localization of endogenous and exogenous EN2 in three PC cell lines (LNCap, PC3, and DU145). We conducted immunohistochemical staining using this homemade antibody, and RT-PCR to detect the expression of EN2 in 25 PC and 25 BPH cases, and analyzed the correlation of EN2 expression and PC clinical staging. RESULTS: The results of WB and immunofluorescence showed our homemade EN2 monoclonal antibody could specifically bind endogenous and exogenous EN2 protein in three different PC cell lines. Endogenous EN2 was generally expressed in the cytoplasm and exogenous EN2 mostly existed in the nucleus of these cell lines. Immunohistochemical staining in PC had extremely stronger signals than that in BPH, suggesting a higher EN2 expression level in PC, which was confirmed by RT-PCR. Interestingly, the stained areas in BPH tissues were mainly in nucleus and cytoplasm, while in PC tissues were mainly on cytomembrane. Moreover, the expression level of EN2 was positively correlated with the PC clinical staging. CONCLUSION: Using our homemade EN2 antibody, we have found different staining patterns and expression level of EN2 in BPH and PC,which may be helpful to predict prostatic disease progression.

[Variation in the vegetation fade stage and its relationships with climate and vegetation productivity in Inner Mongolia, China].

Based on the MODIS NDVI data from 2001 to 2018, we extracted the fade stage of vegetation in Inner Mongolia and the characteristics of its temporal and spatial changes using the Logistic curve maximum curvature method of the cumulative normalized difference vegetation index (NDVI). We analyzed the responses of fade stage to climatic factors and NDVI at the ecological zone level. The results showed that the fade stage in Inner Mongolia occurred between the day of year (DOY) 260 and 280 during the study period. It was DOY 270-280 in the forest ecological zone, and was delayed from the south to north. The fade stage in the grassland ecological zone was the earliest and ranged between DOY 257 and 273, and was delayed from the northeast to southwest. The fade stage in the desert ecological zone ranged between DOY 270 and 283, which was delayed from the northeast to southwest. From 2001 to 2018, the fade stage in three ecological zones showed an insignificant delaying trend. Spatially, vegetation productivity decreased from the northeast to southwest, with a larger area of an increasing temporal trend than that of a decreasing trend. The fade stage in the entire Inner Mongolia and three ecological zones was greatly affected by precipitation during the two or three months before the fade stage and was positively correlated with the pre-season average temperature, maximum temperature, and minimum temperature, respectively. The increases/decreases in vegetation productivity in August and September delayed/advanced the fade stage in entire Inner Mongolia and three ecological zones. In contrast, the increases/decreases in vegetation productivity in June and July advanced/delayed the fade stage in the grassland and desert ecological zone.