Nonthreaded Isomers of Sungsanpin and Ulleungdin Lasso Peptides Inhibit H1299 Cancer Cell Migration.

Lasso peptides are a structurally distinct class of biologically active natural products defined by their short sequences with impressively interlocked tertiary structures. Their characteristic peptide [1]rotaxane motif confers marked proteolytic and thermal resiliency, and reports on their diverse biological functions have been credited to their exceptional sequence variability. Because of these unique properties, taken together with improved technologies for their biosynthetic production, lasso peptides are emerging as a designable scaffold for peptide-based therapeutic discovery and development. Although the defined structure of lasso peptides is recognized for its remarkable properties, the role of the motif in imparting bioactivity is less understood. For example, sungsanpin and ulleungdin are natural lasso peptides that similarly exhibit encouraging cell migration inhibitory activities in A549 lung carcinoma epithelial cells, despite sharing only one-third of the sequence homology. We hypothesized that the shape of the lasso motif is beneficial for the preorganization of the conserved residues, which might be partially retained in variants lacking the threaded structure. Herein, we describe solid-phase peptide synthesis strategies to prepare acyclic, head-to-side chain (branched), and head-to-tail (macrocyclic) cyclic variants based on the sungsanpin (Sun) and ulleungdin (Uln) sequences. Proliferation assays and time-lapse cell motility imaging studies were used to evaluate the cell inhibitory properties of natural Sun compared with the synthetic Sun and Uln isomers. These studies demonstrate that the lasso motif is not a required feature to slow cancer cell migration and more generally show that these nonthreaded isomers can retain similar activity to the natural lasso peptide despite the differences in their overall structures.

Pectointercostal Fascial Block Catheters for Thoracic Injuries: A Case Series.

Providing analgesia for patients with anterior rib and sternum fracture has been addressed from various types of modalities. Regional anesthesia via epidurals or peripheral nerve blocks, opiates, and other forms of multimodal pain regimens have been used. However, in the polytraumatic injury patient, positioning for an epidural may be problematic, and a predominantly opiate-based treatment plan may compromise respiratory status. In this case series, we describe the pectointercostal fascial block as another tool to treat patients with anterior rib and sternal fracture with polytraumatic injuries. All 3 of the block's successes were evident by improvement in the respiratory status of each patient.

Understanding of alkaline pretreatment parameters for corn stover enzymatic saccharification.

BACKGROUND: Previous research on alkaline pretreatment has mainly focused on optimization of the process parameters to improve substrate digestibility. To achieve satisfactory sugar yield, extremely high chemical loading and enzyme dosages were typically used. Relatively little attention has been paid to reduction of chemical consumption and process waste management, which has proven to be an indispensable component of the bio-refineries. To indicate alkali strength, both alkali concentration in pretreatment solution (g alkali/g pretreatment liquor or g alkali/L pretreatment liquor) and alkali loading based on biomass solids (g alkali/g dry biomass) have been widely used. The dual approaches make it difficult to compare the chemical consumption in different process scenarios while evaluating the cost effectiveness of this pretreatment technology. The current work addresses these issues through pretreatment of corn stover at various combinations of pretreatment conditions. Enzymatic hydrolysis with different enzyme blends was subsequently performed to identify the effects of pretreatment parameters on substrate digestibility as well as process operational and capital costs. RESULTS: The results showed that sodium hydroxide loading is the most dominant variable for enzymatic digestibility. To reach 70% glucan conversion while avoiding extensive degradation of hemicellulose, approximately 0.08 g NaOH/g corn stover was required. It was also concluded that alkali loading based on total solids (g NaOH/g dry biomass) governs the pretreatment efficiency. Supplementing cellulase with accessory enzymes such as α-arabinofuranosidase and ß-xylosidase significantly improved the conversion of the hemicellulose by 6-17%. CONCLUSIONS: The current work presents the impact of alkaline pretreatment parameters on the enzymatic hydrolysis of corn stover as well as the process operational and capital investment costs. The high chemical consumption for alkaline pretreatment technology indicates that the main challenge for commercialization is chemical recovery. However, repurposing or co-locating a biorefinery with a paper mill would be advantageous from an economic point of view.

Reducing acid in dilute acid pretreatment and the impact on enzymatic saccharification.

Dilute acid pretreatment is a leading pretreatment technology for biomass to ethanol conversion due to the comparatively low chemical cost and effective hemicellulose solubilization. The conventional dilute acid pretreatment processes use relatively large quantities of sulfuric acid and require alkali for pH adjustment afterwards. Significant amounts of sulfate salts are generated as by-products, which have to be properly treated before disposal. Wastewater treatment is an expensive, yet indispensable part of commercial level biomass-to-ethanol plants. Therefore, reducing acid use to the lowest level possible would be of great interest to the emerging biomass-to-ethanol industry. In this study, a dilute acid pretreatment process was developed for the pretreatment of corn stover. The pretreatment was conducted at lower acid levels than the conventional process reported in the literature while using longer residence times. The study indicates that a 50% reduction in acid consumption can be achieved without compromising pretreatment efficiency when the pretreatment time was extended from 1-5 min to 15-20 min. To avoid undesirable sugar degradation and inhibitor generation, temperatures should be controlled below 170°C. When the sulfuric acid-to-lignocellulosic biomass ratio was kept at 0.025 g acid/g dry biomass, a cellulose-to-glucose conversion of 72.7% can be achieved at an enzyme loading of 0.016 g/g corn stover. It was also found that acid loading based on total solids (g acid/g dry biomass) governs the pretreatment efficiency rather than the acid concentration (g acid/g pretreatment liquid). While the acid loading on lignocellulosic biomass may be achieved through various combinations of solids loading and acid concentration in the pretreatment step, this work shows that it is unlikely to reduce acid use without undermining pretreatment efficiency simply by increasing the solid content in pretreatment reactors, therefore acid loading on biomass is indicated to be the key factor in effective dilute acid pretreatment.