Linaclotide is a 14-amino acid residue peptide approved by the FDA for the treatment of irritable bowel syndrome with constipation (IBS-C), which activates guanylate cyclase C to accelerate intestinal transit. Here we show a new method for the synthesis of linaclotide through the completely selective formation of three disulfide bonds in satisfactory overall yields via mild oxidation reactions of the solid phase and liquid phase, using 4-methoxytrityl (Mmt), diphenylmethyl (Dpm) and 2-nitrobenzyl (O-NBn) protecting groups of cysteine as substrate, respectively.

Global Navigation Satellite System interferometric reflectometry (GNSS-IR), as a new remote sensing detection technology, can retrieve surface soil moisture (SM) by separating the modulation terms from the effective signal-to-noise ratio (SNR) data. However, traditional low-order polynomials are prone to over-fitting when separating modulation terms. Moreover, the existing research mainly relies on prior information to select satellites for SM retrieval. Accordingly, this study proposes a method based on empirical modal decomposition (EMD) and cross-correlation satellite selection (CCSS) for SM retrieval. This method intended to adaptively separate the modulation terms of SNR through the combination of EMD and an intrinsic mode functions (IMF) discriminant method, then construct a CCSS method to select available satellites, and finally establish a multisatellite robust estimation regression (MRER) model to retrieve SM. The results indicated that with EMD, the different feature components implied in the SNR data of different satellites could be adaptively decomposed, and the trend and modulation terms of the SNR could more accurately be acquired by the IMF discriminant method. The available satellites could be efficiently selected through CCSS, and the SNR quality of different satellites could also be classified at different accuracy levels. Furthermore, MRER could fuse the multisatellite phases well, which enhanced the accuracy of SM retrieval and further verified the feasibility and effectiveness of combining EMD and CCSS. When rm=0.600 and rn=0.700, the correlation coefficient (r) of the multisatellite combination reached 0.918, an improvement of at least 40% relative to the correlation coefficient of a single satellite. Therefore, this method can improve the adaptive ability of SNR decomposition, and the selection of satellites has high flexibility, which is helpful for the application and popularization of the GNSS-IR technology.

The global navigation satellite system–interferometric reflectometry (GNSS-IR) technique has emerged as an effective coastal sea-level monitoring solution. However, the accuracy and stability of GNSS-IR sea-level estimation based on quadratic fitting are limited by the retrieval range of reflector height (RH range) and satellite-elevation range, reducing the flexibility of this technology. This study introduces a new GNSS-IR sea-level estimation model that combines local mean decomposition (LMD) and Lomb–Scargle periodogram (LSP). LMD can decompose the signal-to-noise ratio (SNR) arc into a series of signal components with different frequencies. The signal components containing information from the sea surface are selected to construct the oscillation term, and its frequency is extracted by LSP. To this end, observational data from SC02 sites in the United States are used to evaluate the accuracy level of the model. Then, the performance of LMD and the influence of noise on retrieval results are analyzed from two aspects: RH ranges and satellite-elevation ranges. Finally, the sea-level variation for one consecutive year is estimated to verify the stability of the model in long-term monitoring. The results show that the oscillation term obtained by LMD has a lower noise level than other signal separation methods, effectively improving the accuracy of retrieval results and avoiding abnormal values. Moreover, it still performs well under loose constraints (a wide RH range and a high-elevation range). In one consecutive year of retrieval results, the new model based on LMD has a significant improvement effect over quadratic fitting, and the root mean square error and mean absolute error of retrieval results obtained in each month on average are improved by 8.34% and 8.87%, respectively.