Nucleophilic Aromatic Substitution of Heteroaryl Halides with Thiols.

The nucleophilic aromatic substitution (SNAr) between heteroaryl halides (Cl, Br) and thiols proceeds smoothly in DMAc under the action of K2CO3 at rt-100 °C. For most electron-deficient heteroarenes, reaction takes place without introducing an additional electron-withdrawing group. For electron-rich heteroarenes, an additional electron-withdrawing group such as a simple ester, keto, cyano, and nitro group is required to ensure the reaction completes. The reactivity trend of heteroaryl halides is highly dependent on the electronic nature of the heteroarenes and orientation of halogens. Besides thiols, a couple of functionalized thioureas and thioamides are compatible with these conditions, providing the corresponding heteroaryl thioethers in good yields.

Clinical relevance of SCN and CyN induced by ELANE mutations: a systematic review.

Introduction: According to the PRISMA criteria, a systematic review has been conducted to investigate the clinical relevance between patients with severe congenital neutropenia (SCN) and cyclic congenital neutropenia (CyN) induced by ELANE mutations. Methods: We have searched PubMed, EMBASE, Web of Science, Scopus, Cochrane, CNKI, Wanfang Medicine, and VIP for ELANE mutation related literature published from 1997 to 2022. Using Microsoft Excel collect and organize data, SPSS 25, GraphPad Prism 8.0.1, and Omap analyze and plot statistical. Compare the gender, age, geography, mutation sites, infection characteristics, treatment, and other factors of SCN and CyN patients induced by ELANE mutations, with a focus on exploring the relationship between genotype and clinical characteristics, genotype and prognosis. Results: This study has included a total of 467 patients with SCN and 90 patients with CyN. The onset age of SCN and CyN are both less than 1 year old, and the onset and diagnosis age of SCN are both younger than CyN. The mutation of ELANE gene is mainly missense mutation, and hot spot mutations include S126L, P139L, G214R, c.597+1G>A. The high-frequency mutations with severe outcomes are A57V, L121H, L121P, c.597+1G>A, c.597+1G>T, S126L, C151Y, C151S, G214R, C223X. Respiratory tract, skin and mucosa are the most common infection sites, Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli are the most common. Discussion: Patients with refractory G-CSF are more likely to develop severe outcomes. The commonly used pre-treatment schemes for transplantation are Bu-Cy-ATG and Flu-Bu-ATG. The prognosis of transplantation is mostly good, but the risk of GVHD is high. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/. PROSPERO, identifier CRD42023434656.

Effects of different levels of dietary crude protein on the physiological response, reproductive performance, blood profiles, milk composition and odor emission in gestating sows.

OBJECTIVE: This study was conducted to evaluate the effects of crude protein (CP) levels on the physiological response, reproductive performance, blood profiles, milk composition and odor emission in gestating sows. METHODS: Seventy-two multiparous sows (Yorkshire×Landrace) of average body weight (BW), backfat thickness, and parity were assigned to one of six treatments with 10 or 11 sows per treatment in a completely randomized design. Experimental diets with different CP levels were as follows: i) CP11, corn‒soybean-based diet containing 11% CP; ii) CP12, corn‒soybean-based diet containing 12% CP; iii) CP13, corn‒soybean-based diet containing 13% CP; iv) CP14, corn‒soybean-based diet containing 14% CP; v) CP15, corn‒soybean-based diet containing 15% CP; and vi) CP16: corn‒soybean-based diet containing 16% CP. RESULTS: There was no significant difference in the performance of sow or piglet growth when sows were fed different dietary protein levels. Milk fat (linear, p = 0.05) and total solids (linear, p = 0.04) decreased as dietary CP levels increased. Increasing dietary CP levels in the gestation diet caused a significant increase in creatinine at days 35 and 110 of gestation (linear, p = 0.01; linear, p = 0.01). The total protein in sows also increased as dietary CP levels increased during the gestation period and 24 hours postpartum (linear, p = 0.01; linear, p = 0.01). During the whole experimental period, an increase in urea in sows was observed when sows were fed increasing levels of dietary CP (linear, p = 0.01), and increasing blood urea nitrogen (BUN) concentrations were observed as well. In the blood parameters of piglets, there were linear improvements in creatinine (linear, p = 0.01), total protein (linear, p = 0.01), urea (linear, p = 0.01), and BUN (linear, p = 0.01) with increasing levels of dietary CP as measured 24 hours postpartum. At two measurement points (days 35 and 110) of gestation, the odor gas concentration, including amine, ammonia, and hydrogen sulfide, increased linearly when sows fed diets with increasing levels of dietary CP (linear, p = 0.01). Moreover, as dietary CP levels increased to 16%, the odor gas concentration was increased with a quadratic response (quadratic, p = 0.01). CONCLUSION: Reducing dietary CP levels from 16% to 11% in a gestating diet did not exert detrimental effects on sow body condition or piglet performance. Moreover, a low protein diet (11% CP) may improve dietary protein utilization and metabolism to reduce odor gas emissions in manure and urine in gestating sows.

α-Amino Acids and Peptides as Bifunctional Reagents: Carbocarboxylation of Activated Alkenes via Recycling CO2.

Carboxylic acids, including amino acids (AAs), have been widely used as reagents for decarboxylative couplings. In contrast to previous decarboxylative couplings that release CO2 as a waste byproduct, herein we report a novel strategy with simultaneous utilization of both the alkyl and carboxyl components from carboxylic acids. Under this unique strategy, carboxylic acids act as bifunctional reagents in the redox-neutral carbocarboxylation of alkenes. Diverse, inexpensive, and readily available α-AAs take part in such difunctionalizations of activated alkenes via visible-light photoredox catalysis, affording a variety of valuable but otherwise difficult to access γ-aminobutyric acid derivatives (GABAs). Additionally, a series of dipeptides and tripeptides also participate in this photocatalytic carbocarboxylation. Although several challenges exist in this system due to the low concentration and quantitative amount of CO2, as well as unproductive side reactions such as hydrodecarboxylation of the carboxylic acids and hydroalkylation of the alkenes, excellent regioselectivity and moderate to high chemoselectivity are achieved. This process features low catalyst loading, mild reaction conditions, high step and atom economy, and good functional group tolerance, and it is readily scalable. The resulting products are subject to efficient derivations, and the overall process is amenable to applications in the late-stage modification of complex compounds. Mechanistic studies indicate that a carbanion is generated catalytically and it acts as the key intermediate to react with CO2, which is also generated catalytically in situ and thus remains in low concentration. The overall transformation represents an efficient and sustainable system for organic synthesis, pharmaceutics, and biochemistry.