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LCZ696 is a novel treatment for patients suffering from heart failure that combines the two active pharmaceutical ingredients sacubitril and valsartan in a single chemical compound. While valsartan is an established drug substance, a new manufacturing process suitable for large-scale commercial production had to be developed for sacubitril. The use of chemocatalysis, biocatalysis, and flow chemistry as state-of-the-art technologies allowed to efficiently build up the structure of sacubitril and achieve the defined performance targets.

Background: Upper tract urinary carcinoma (UTUC) is a relatively uncommon but aggressive disease. The Ki-67 antigen is a classic marker of cellular proliferation, but there is still controversy regarding the significance and importance of Ki-67 in tumor progression. Methods: In this study, we first detected Ki-67 expression in UTUC patients by immunohistochemistry (IHC). Subsequently, we quantitatively combined the results with those from the published literature in a meta-analysis after searching several databases. Results: IHC results demonstrated that patients with muscle-invasive tumors (T2-T4) had higher Ki-67 expression than those with non-muscle-invasive tumors (Tis-T1), suggesting that high Ki-67 expression may be associated with the aggressive form of UTUC. Kaplan-Meier curves showed that patients with high Ki-67 expression had significantly poorer cancer-specific survival (CSS) and disease-free survival (DFS). Furthermore, multivariate analysis suggested that Ki-67 expression was an independent prognostic factor for CSS (hazard ratio, HR=3.196) and DFS (HR=3.517) in UTUC patients. Then, a meta-analysis of the published literature investigating Ki-67 expression and its effects on UTUC prognosis was conducted. After searching the PubMed, Medline, Embase, Cochrane Library and Scopus databases, 12 articles met the eligibility criteria for this analysis. The B. Fan and H. Zhang contributed equally to this work.

Slippery liquid-infused porous surfaces (SLIPSs) are widely used as an effective passive approach to reduce icing disasters. However, various porous structures make SLIPSs exhibit different droplet mobility and lubricant stability. Undoubtedly, the substrate surface has a great impact on the durable anti-icing of SLIPSs. Herein, surfaces with different pore sizes and porosities were prepared to study their effects on the performance of SLIPS. The results show that small pores and high porosity are beneficial for the preparation of durable anti-icing SLIPS. The small pore size (about 100 nm) has a strong capillary pressure on the lubricant, and the surface with high porosity (66%) possesses a large lubricant–liquid contact ratio. These two can greatly improve the lubricant stability of SLIPS and achieve rapid self-healing. The SLIPS prepared by a suitable porous surface shows excellent anti-icing performance in the simulated glaze ice and durable anti-icing ability in the long-term icing/deicing cycles. In detail, the prepared SLIPS experiences more than 140 icing/deicing cycles through four effective self-healing while maintaining extremely low ice adhesion (<20 kPa). This work proposes a certain improved SLIPS with small pores and high porosity to achieve excellent durable anti-icing performance, broadening the practical applications of SLIPS.