A highly efficient, two-step, one-pot synthetic strategy for amides and peptides was developed by employing ynamides as novel coupling reagents under extremely mild reaction conditions. The ynamides not only are effective for simple amide and dipeptide synthesis but can also be used for peptide segment condensation. Importantly, no racemization was detected during the activation of chiral carboxylic acids. Excellent amidation selectivity toward amino groups in the presence of -OH, -SH, -CONH, ArNH, and the NH of indole was observed, making the protection of these functional groups unnecessary in amide and peptide synthesis.

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Background Three-dimensional T1 magnetization prepared rapid acquisition gradient echo (3D-T1-MPRAGE) is preferred in detecting brain metastases (BM) among MRI. We developed an automatic deep learning–based detection and segmentation method for BM (named BMDS net) on 3D-T1-MPRAGE images and evaluated its performance. Methods The BMDS net is a cascaded 3D fully convolution network (FCN) to automatically detect and segment BM. In total, 1652 patients with 3D-T1-MPRAGE images from 3 hospitals (n = 1201, 231, and 220, respectively) were retrospectively included. Manual segmentations were obtained by a neuroradiologist and a radiation oncologist in a consensus reading in 3D-T1-MPRAGE images. Sensitivity, specificity, and dice ratio of the segmentation were evaluated. Specificity and sensitivity measure the fractions of relevant segmented voxels. Dice ratio was used to quantitatively measure the overlap between automatic and manual segmentation results. Paired samples t-tests and analysis of variance were employed for statistical analysis. Results The BMDS net can detect all BM, providing a detection result with an accuracy of 100%. Automatic segmentations correlated strongly with manual segmentations through 4-fold cross-validation of the dataset with 1201 patients: the sensitivity was 0.96 ± 0.03 (range, 0.84–0.99), the specificity was 0.99 ± 0.0002 (range, 0.99–1.00), and the dice ratio was 0.85 ± 0.08 (range, 0.62–0.95) for total tumor volume. Similar performances on the other 2 datasets also demonstrate the robustness of BMDS net in correctly detecting and segmenting BM in various settings. Conclusions The BMDS net yields accurate detection and segmentation of BM automatically and could assist stereotactic radiotherapy management for diagnosis, therapy planning, and follow-up.

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BACKGROUND: Poly(lactic acid) (PLA), coming from renewable resources, can be used to solve environmental problems. However, PLA has to have a relatively high molecular weight in order to have acceptable mechanical properties as required in many applications. Chain-extension reaction is an effective method to raise the molecular weight of PLA. RESULTS: A high molecular weight biodegradable lactic acid polymer was successfully synthesized in two steps.First, the lactic acid monomer was oligomerized to low molecular weight hydroxyl-terminated prepolymer; the molecular weight was then increased by chain extension using 1,6-hexamethylene diisocyanate as the chain extender. The polymer was characterized using 1 H NMR analysis, gel permeation chromatography, differential scanning calorimetry and Fourier transform infrared spectroscopy. The results showed that the obtained polymer had a M n of 27 500 g mol −1 and a M w of 116 900 g mol −1 after 40 min of chain extension at 180 • C. The glass transition temperature (T g ) of the low molecular weight prepolymer was 47.8 • C. After chain extension, T g increased to 53.2 • C. The mechanical and rheological properties of the obtained polymer were also investigated. CONCLUSION:The results suggest that high molecular weight PLA can be achieved by chain extension to meet conventional uses.

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Chronic wounds caused by diabetic or venous diseases remain a social and healthcare burden. In this work, a new strategy is proposed in which injectable thermosensitive chitosan/collagen/β-glycerophosphate (β-GP) hydrogels were combined with three-dimensional mesenchymal stem cell (3D MSC) spheroids to accelerate chronic wound healing by enhanced vascularization and paracrine effects. Chitosan/collagen/β-GP solution mixed with 3D MSC spheroids was rapidly transformed to a gel at body temperature by physical cross-linking, then overlapped the wounds fully and fitted to any shape of the wound. The results showed that the combination therapy exhibited a markedly therapeutic effect than the hydrogel-loaded two-dimensional (2D) MSCs or 2D MSCs alone. The hydrogel could provide an environment conductive to the attachment and proliferation of encapsulated MSCs, especially accelerating the proliferation and paracrine factor secretion of 3D MSC spheroids. These results supplied a novel alternative approach to treat chronic wounds caused by diabetic or venous diseases.