Alkene dialkylation by triple radical sorting.

The development of bimolecular homolytic substitution (SH2) catalysis has expanded cross-coupling chemistries by enabling the selective combination of any primary radical with any secondary or tertiary radical through a radical sorting mechanism1-8. Biomimetic9,10 SH2 catalysis can be used to merge common feedstock chemicals-such as alcohols, acids and halides-in various permutations for the construction of a single C(sp3)-C(sp3) bond. The ability to sort these two distinct radicals across commercially available alkenes in a three-component manner would enable the simultaneous construction of two C(sp3)-C(sp3) bonds, greatly accelerating access to complex molecules and drug-like chemical space11. However, the simultaneous in situ formation of electrophilic and primary nucleophilic radicals in the presence of unactivated alkenes is problematic, typically leading to statistical radical recombination, hydrogen atom transfer, disproportionation and other deleterious pathways12,13. Here we report the use of bimolecular homolytic substitution catalysis to sort an electrophilic radical and a nucleophilic radical across an unactivated alkene. This reaction involves the in situ formation of three distinct radical species, which are then differentiated by size and electronics, allowing for regioselective formation of the desired dialkylated products. This work accelerates access to pharmaceutically relevant C(sp3)-rich molecules and defines a distinct mechanistic approach for alkene dialkylation.

Triple Radical Sorting: Aryl-Alkylation of Alkenes.

The cross-coupling of aryl bromides with alkenes can provide access to diverse combinatorial chemical space. Two-component couplings between these partners are well-known, but three-component aryl-functionalizations of unactivated alkenes remain underdeveloped. In particular, the aryl-alkylation of unactivated alkenes would allow for rapid construction of molecular complexity and the expedient exploration of a pharmaceutically relevant and C(sp3)-rich structural landscape. Herein, we report a general approach toward the aryl-alkylation of alkenes through a triple radical sorting mechanism. Over the course of the reaction, a high energy aryl radical, a primary radical, and a hindered alkyl radical are simultaneously formed. Through mediation by a nickel-based catalyst, the three radicals are sorted into productive bond-forming pathways toward the efficient aryl-alkylation of alkenes. A wide range of electronically and sterically differentiated alkenes and aryl radical precursors can be used to access complex scaffolds. This method was further applied to the synthesis of highly substituted semisaturated fused heterocycles.

Copper-Catalyzed Coupling of Alkyl Vicinal Bis(boronic Esters) to an Array of Electrophiles.

A neighboring boronate group in the substrate provides a dramatic rate acceleration in transmetalation to copper and thereby enables organoboronic esters to participate in unprecedented site-selective cross-couplings. This cross-coupling operates under practical experimental conditions and allows for coupling between vicinal bis(boronic esters) and allyl, alkynyl, and propargyl electrophiles as well as a simple proton. Because the reactive substrates are vicinal bis(boronic esters), the cross-coupling described herein provides an expedient new method for the construction of boron-containing reaction products from alkenes. Mechanistic experiments suggest that chelated cyclic ate complexes may play a role in the transmetalation.

Gray Matter Age Prediction as a Biomarker for Risk of Dementia.

The gap between predicted brain age using magnetic resonance imaging (MRI) and chronological age may serve as a biomarker for early-stage neurodegeneration. However, owing to the lack of large longitudinal studies, it has been challenging to validate this link. We aimed to investigate the utility of such a gap as a risk biomarker for incident dementia using a deep learning approach for predicting brain age based on MRI-derived gray matter (GM). We built a convolutional neural network (CNN) model to predict brain age trained on 3,688 dementia-free participants of the Rotterdam Study (mean age 66 ± 11 y, 55% women). Logistic regressions and Cox proportional hazards were used to assess the association of the age gap with incident dementia, adjusted for age, sex, intracranial volume, GM volume, hippocampal volume, white matter hyperintensities, years of education, and APOE ε4 allele carriership. Additionally, we computed the attention maps, which shows which regions are important for age prediction. Logistic regression and Cox proportional hazard models showed that the age gap was significantly related to incident dementia (odds ratio [OR] = 1.11 and 95% confidence intervals [CI] = 1.05-1.16; hazard ratio [HR] = 1.11, and 95% CI = 1.06-1.15, respectively). Attention maps indicated that GM density around the amygdala and hippocampi primarily drove the age estimation. We showed that the gap between predicted and chronological brain age is a biomarker, complimentary to those that are known, associated with risk of dementia, and could possibly be used for early-stage dementia risk screening.

Alcohols as Alkylating Agents: Photoredox-Catalyzed Conjugate Alkylation via In Situ Deoxygenation.

The rapid exploration of sp3 -enriched chemical space is facilitated by fragment-coupling technologies that utilize simple and abundant alkyl precursors, among which alcohols are a highly desirable, commercially accessible, and synthetically versatile class of substrate. Herein, we describe an operationally convenient, N-heterocyclic carbene (NHC)-mediated deoxygenative Giese-type addition of alcohol-derived alkyl radicals to electron-deficient alkenes under mild photocatalytic conditions. The fragment coupling accommodates a broad range of primary, secondary, and tertiary alcohol partners, as well as structurally varied Michael acceptors containing traditionally reactive sites, such as electrophilic or oxidizable moieties. We demonstrate the late-stage diversification of densely functionalized molecular architectures, including drugs and biomolecules, and we further telescope our protocol with metallaphotoredox cross-coupling for step-economic access to sp3 -rich complexity.

Diastereo- and Enantioselective 1,4-Difunctionalization of Borylenynes by Catalytic Conjunctive Cross-Coupling.

Enantioselective conjunctive cross-coupling of enyne-derived boronate complexes occurs with 1,4 addition of the electrophile and migrating group across the π system. This reaction pathway furnishes α-boryl allenes as the reaction product. In the presence of a chiral catalyst, both the central and axial chirality of the product can be controlled during product formation.

Silicon decorated cone shaped carbon nanotube clusters for lithium ion battery anodes.

In this work, we report the synthesis of an three-dimensional (3D) cone-shape CNT clusters (CCC) via chemical vapor deposition (CVD) with subsequent inductively coupled plasma (ICP) treatment. An innovative silicon decorated cone-shape CNT clusters (SCCC) is prepared by simply depositing amorphous silicon onto CCC via magnetron sputtering. The seamless connection between silicon decorated CNT cones and graphene facilitates the charge transfer in the system and suggests a binder-free technique of preparing lithium ion battery (LIB) anodes. Lithium ion batteries based on this novel 3D SCCC architecture demonstrates high reversible capacity of 1954 mAh g(-1) and excellent cycling stability (>1200 mAh g(-1) capacity with ≈ 100% coulombic efficiency after 230 cycles).

Comprehensive analysis of laparoscopic, robotic, and open hepatectomy outcomes using the nationwide readmissions database.

Although open resections have been the most prevalent method of hepatectomies in the United States, laparoscopic and robotic methods of liver resection have since gained significant traction. Given the augmenting role of minimally invasive techniques in liver resection, a study that explores and analyzes the surgical outcomes of the approaches mentioned above to liver resection on a national basis is warranted. A retrospective analysis was performed in this study using the 2016-2018 Nationwide Readmissions Database (NRD). Patients who underwent liver resections via one of the following methods were selected and grouped: open, laparoscopic, or robotic. Our primary outcome variable of interest was the 45-day readmission rate. 11,186 patients were included in the analysis. The 45-day readmission rate was 13.5%, 12.9%, and 8.7% in the open, laparoscopic, and robotic groups, respectively (p < 0.001). A significantly lower complication rate (7.3%) was seen in the robotic group than its counterparts (11.4% in open vs. 9.1% in the laparoscopic group). Patients undergoing hepatectomies may benefit from the robotic approach given that it is associated with a shorter hospital length of stay and lower readmission rates.

Long-Term Suitability of Left Gastric Artery Inflow for Arterial Perfusion of Living Donor Right Lobe Grafts.

Poorer than expected, living donor liver transplant outcomes are observed after recipient graft artery thrombosis. At grafting, the risk for later thrombosis is high if a dissected hepatic artery is used for standard reconstruction. Surgeon diagnosis of dissection requires nonstandard management with alternative technique in addition to microvascular expertise. Intimal flap repair with standard reconstruction is contingent on basis of a redo anastomosis. It is a suboptimal choice for living donor transplantation. Achieving goal graft arterial perfusion at first revascularization is crucial for superior outcomes. Managing dissection at grafting with nonstandard left gastric artery reconstruction is unreported. Our experience is limited, but this is our preferred alternative technique to standard hepatic artery reconstruction complicated by dissection. Here, we describe our two-case experience with left gastric arterialized grafts for management of dissection. Our living donor graft recipients with alternatively arterialized grafts are now 6- and 2-years posttransplant.

Candida invasion and influences in smoking patients with multiple oral leucoplakias--a retrospective study.

Treating patients with multiple oral leucoplakias (MOLs) who smoke is more difficult and complicated than treating those with single oral leucoplakia (SOL). Removing the aetiological factors causing MOL can effectively prevent its recurrence. The aim was to study the infection by and influences of Candida in smoking patients with MOLs. A retrospective study was conducted on 136 smoking patients who had clinicopathological OLs. Among these patients, 73 lesions in 31 patients were MOLs, while 105 patients had SOLs. All patients were treated by complete resection. All specimens were tested for epithelial dysplasia, and stained with periodic acid-Schiff reagent. The rate of MOL concurrence with candidal infection was higher than that of SOLs. The incidence of Candida associated with MOLs was higher for recurrent than for non-recurrent lesions. The disease-free time was shorter in MOL patients with candidal infection. Moreover, MOLs with candidal infection were more likely to have an increasing ratio to combine with epithelial dysplasia. Candida is an important risk factor in smoking patients with MOLs. Microscopic and fungal examinations of those lesions should permit a detailed diagnosis in such patients and for long-term predictive assessments.