Remote functionalization of alkenes via chain walking has generally been limited to C(sp
)-H bonds α and β to polar-functional units, while γ-C(sp
)-H functionalization through controlled alkene ...transposition is a longstanding challenge. Herein, we describe NiH-catalyzed migratory formal hydroamination of alkenyl amides achieved via chelation-assisted control, whereby various amino groups are installed at the γ-position of aliphatic chains. By tuning olefin isomerization and migratory hydroamination through ligand and directing group optimization, γ-selective amination can be achieved via stabilization of a 6-membered nickellacycle by an 8-aminoquinoline directing group and subsequent interception by an aminating reagent. A range of amines can be installed at the γ-C(sp
)-H bond of unactivated alkenes with varying alkyl chain lengths, enabling late-stage access to value-added γ-aminated products. Moreover, by employing picolinamide-coupled alkene substrates, this approach is further extended to δ-selective amination. The chain-walking mechanism and pathway selectivity are investigated by experimental and computational methods.
Chelation‐assisted C−H bond and alkene functionalization using bidentate directing groups offers an elegant and versatile approach to overcome regiocontrol issues by allowing the catalyst to come ...into close proximity with the targeted sites. In this personal account, we highlight our recent works in developing regio‐ and stereocontrolled functionalizations through transition‐metal catalysis enabled by bidentate directing groups. We classify our results into two categories: (1) regioselective alkene functionalization using bidentate directing groups, and (2) asymmetric C–H functionalization using chiral bidentate directing groups. Furthermore, density functional theory studies to elucidate the origin of the regio‐ and stereoselectivity exerted by bidentate directing groups are discussed.
This personal account focuses on the recent development of regioselective alkene functionalization through transition‐metal catalysis enabled by bidentate directing groups. Asymmetric C−H functionalization using chiral bidentate directing groups is also highlighted.
Cancer stem cells are critical for cancer initiation, development, and treatment resistance. Our understanding of these processes, and how they relate to glioblastoma heterogeneity, is limited. To ...overcome these limitations, we performed single-cell RNA sequencing on 53586 adult glioblastoma cells and 22637 normal human fetal brain cells, and compared the lineage hierarchy of the developing human brain to the transcriptome of cancer cells. We find a conserved neural tri-lineage cancer hierarchy centered around glial progenitor-like cells. We also find that this progenitor population contains the majority of the cancer's cycling cells, and, using RNA velocity, is often the originator of the other cell types. Finally, we show that this hierarchal map can be used to identify therapeutic targets specific to progenitor cancer stem cells. Our analyses show that normal brain development reconciles glioblastoma development, suggests a possible origin for glioblastoma hierarchy, and helps to identify cancer stem cell-specific targets.
This is a pilot study that investigated differences in effectiveness, maintenance of effectiveness, cost-efficiency, satisfaction, and usability of a lottery incentive via mobile devices to promote ...walking, depending on the chance of winning the lottery, the amount of the prize, and gender. Sixty-six college students (male = 26) were randomly assigned to 3 groups: 10% chance of a big prize (10% + B), 50% chance of a medium prize (50% + M), and 100% chance of a small prize (100% + S). Step counts were collected through mobile devices before and after the intervention, as well as at the 2-month follow-up. The results showed significant increases in the step counts among males after the intervention in the 10% + B and the 50% + M groups, and females in the 100% + S group. Only males in the 50% + M group exhibited maintenance in effectiveness during follow-up. With regard to cost-efficiency, the 10% + B and the 50% + M male groups, which showed significant differences in effectiveness, were compared, and no significant difference was found. With regard to intervention satisfaction, satisfaction of the 10% + B group was lower than that of the 100% + S group. There were no significant interactions or main effects regarding the usability of the intervention. The results suggest that a lottery incentive is effective only for men to promote walking when a medium size prize is given with a 50% of chance of winning the lottery.
Group contingency (GC) is an effective and cost-efficient strategy that can be successfully applied to technology-based interventions. This study examined the relative effectiveness and cost ...efficiency of three types of technology-based group contingencies on walking among adults. Seventy two students were divided into teams of three. Each team was randomly assigned to one of three GC conditions (independent, interdependent, or dependent) and underwent 66 days of technology-based group contingency intervention. Sixty five participants completed the intervention and 61 completed the follow-up assessment 2 months later. Step counts and self-reported walking activity increased after the intervention under all three conditions. The proportion of participants that met the target step counts was significantly higher under the dependent group contingency condition. However, 2 months later, intervention effects were not maintained under any condition. For cost efficiency, the increase in step count per point was significantly higher under the interdependent group contingency condition. Group cohesion and social validity (point satisfaction and point utility) were significantly higher under the dependent group contingency condition. Finally, the clinical implications and limitations of this study are discussed.
An early and accurate diagnosis of Candida albicans is critical for the rapid antifungal treatment of candidemia, a mortal bloodstream infection. This study demonstrates viscoelastic microfluidic ...techniques for continuous separation, concentration, and subsequent washing of Candida cells in the blood. The total sample preparation system contains two-step microfluidic devices: a closed-loop separation and concentration device and a co-flow cell-washing device. To determine the flow conditions of the closed-loop device, such as the flow rate factor, a mixture of 4 and 13 μm particles was used. Candida cells were successfully separated from the white blood cells (WBCs) and concentrated by 74.6-fold in the sample reservoir of the closed-loop system at 800 μL/min with a flow rate factor of 3.3. In addition, the collected Candida cells were washed with washing buffer (deionized water) in the microchannels with an aspect ratio of 2 at a total flow rate of 100 μL/min. Finally, Candida cells at extremely low concentrations (Ct > 35) became detectable after the removal of WBCs, the additional buffer solution in the closed-loop system (Ct = 30.3 ± 1.3), and further removal of blood lysate and washing (Ct = 23.3 ± 1.6).
A 48-year-old woman was referred to the ophthalmology department with a 6-month history of blurry vision in her left eye. Her visual acuity was 6/6 in her right eye and 6/18 in her left eye using the ...Snellen chart, with decreased colour vision in her left eye. We performed the swinging flashlight test, which showed a left relative afferent pupillary defect. Her left optic nerve showed temporal pallor. We conducted an automated Humphrey visual field test and found a superotemporal defect and diffuse vision loss in her right and left eyes, respectively. In our patient, the presence of a relative afferent pupillary defect was an important indicator of optic nerve dysfunction, and visual field examinations helped localize the pathology along the visual pathway.
Primary chondrosarcomas of the nasal septum are rare, with a variety of clinical features that evade detection and treatment. While endoscopic surgery has become increasingly accessible, open ...approaches may be needed to provide adequate visualization for tumour ablation and reconstruction. We report the resection and reconstructive considerations of a septal chondrosarcoma.
A 75-year-old woman presented with a 3-year history of a slow growing, firm mass in the nasal tip causing protrusion and septal fullness. Computed Tomography scan of the paranasal sinuses revealed a well-circumscribed, 2.2 cm mass at the anterior nasal septum extending into the right vestibule. Biopsy of the cartilaginous lesion confirmed the diagnosis of a low-grade chondrosarcoma by histopathology. The tumour was removed using a transcolumellar open rhinoplasty approach with a large septal resection. Primary reconstruction of the surgical defect was performed using an L-shaped strut from the nasal keystone area to the columella. Follow-up examinations demonstrated no evidence of recurrent disease with satisfactory functional and cosmetic outcomes at 1-year.
This report describes a case of nasal septal chondrosarcoma successfully treated with surgical excision using an open rhinoplasty approach. Only 5-10% of chondrosarcomas are located in the head and neck region and arise rarely in the nasal septum in approximately 2-4%. With this mass, an open rhinoplasty approach was required to allow optimal exposure of the margins and to facilitate reconstruction without disruption of normal sinonasal anatomy and function. Although rare, chondrosarcoma of the nasal septum should be considered in the differential diagnosis of nasal masses.
The asymmetric addition of an N-H bond to various alkenes via a direct catalytic method is a powerful way of synthesizing value-added chiral amines. Therefore, the enantio- and regioselective ...hydroamination of unactivated alkenes remains an appealing goal. Here, we report the highly enantio- and regioselective Ni-catalyzed hydroamination of readily available unactivated alkenes bearing weakly coordinating native amides or esters. This method succeeds for both terminal and internal unactivated alkenes and has a broad amine coupling partner scope. The mild reaction process is well suited for the late-stage functionalization of complex molecules and has the potential to gain modular access to enantioenriched β- or γ-amino acid derivatives and 1,2- or 1,3-diamines. Mechanistic studies reveal that a chiral bisoxazoline-bound Ni specie effectively leverages carbonyl coordination to achieve enantio- and regioselective NiH insertion into alkenes.
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