Because the backbone of most organic molecules is composed primarily of carbon-carbon bonds, the development of efficient methods for their construction is one of the central challenges of organic ...synthesis. Transition metal-catalyzed cross-coupling reactions between organic electrophiles and nucleophiles serve as particularly powerful tools for achieving carbon-carbon bond formation. Until recently, the vast majority of cross-coupling processes had used either aryl or alkenyl electrophiles as one of the coupling partners. In the past 15 years, versatile new methods have been developed that effect cross-couplings of an array of alkyl electrophiles, thereby greatly expanding the diversity of target molecules that are readily accessible. The ability to couple alkyl electrophiles opens the door to a stereochemical dimension-specifically, enantioconvergent couplings of racemic electrophiles-that substantially enhances the already remarkable utility of cross-coupling processes.
Alkylboron compounds are an important family of target molecules, serving as useful intermediates, as well as end points, in fields such as pharmaceutical science and organic chemistry. Facile ...transformation of carbon-boron bonds into a wide variety of carbon-X bonds (where X is, for example, carbon, nitrogen, oxygen, or a halogen), with stereochemical fidelity, renders the generation of enantioenriched alkylboronate esters a powerful tool in synthesis. Here we report the use of a chiral nickel catalyst to achieve stereoconvergent alkyl-alkyl couplings of readily available racemic α-haloboronates with organozinc reagents under mild conditions. We demonstrate that this method provides straightforward access to a diverse array of enantioenriched alkylboronate esters, in which boron is bound to a stereogenic carbon, and we highlight the utility of these compounds in synthesis.
The development of efficient methods for the generation of enantioenriched sulfonamides and sulfones is an important objective for fields such as organic synthesis and medicinal chemistry; however, ...there have been relatively few reports of direct catalytic asymmetric approaches to controlling the stereochemistry of the sulfur-bearing carbon of such targets. In this report, we describe nickel-catalyzed stereoconvergent Negishi arylations and alkenylations of racemic α-bromosulfonamides and -sulfones that furnish the desired cross-coupling product in very good ee and yield for an array of reaction partners. Mechanistic studies are consistent with the generation of a radical intermediate that has a sufficient lifetime to diffuse out of the solvent cage and to cyclize onto a pendant olefin.
The identities and properties of ‘Novichok’ (Russian for ‘newcomer’ or ‘novice’) agents allegedly used in the recent terrorist attack in the UK have not been well documented. Although several people ...previously involved in the synthesis of these materials claimed Novichok agents to be five to eight times more potent than VX, a deadly nerve agent, no open data on these species are currently available. To bridge this gap, we herein performed a theoretical study on several Novichok agent candidates and conducted natural population charge analysis to evaluate the possible mechanisms of their toxicity, suggesting that these agents might promote the ageing and deformation of acetylcholinesterase. Moreover, the reaction of Novichok agents with acetylcholinesterase serine was calculated to be most thermodynamically favoured for Novichok candidate A234. Thus, this work is believed to provide a basis for finding Novichok antidotes and should inspire further detoxification studies to prepare for possible terrorist attacks in the future.
During cancer resection surgeries, intraoperative histopathologic examination of the surgical specimen is crucial for tumor margin identification. A conventional frozen‐section analysis requires ...complex tissue processing, which prolongs surgery and potentially introduces interpretation errors. Here, as a novel approach to label‐free intraoperative histopathology, a high‐speed reflection‐mode ultraviolet photoacoustic microscopy (UV‐PAM) system employing a waterproof 1‐axis microelectromechanical systems scanner is demonstrated. Label‐free nuclear imaging is photoacoustically verified using tissue sections excised from mice and humans. Moreover, by imaging clinical specimens from cancer patients and numerically quantifying the histopathologic results, it is successfully demonstrated that the proposed UV‐PAM system has great potential as an alternative intraoperative histopathology method with minimal tissue preparation processes.
Here, high‐speed, label‐free, and non‐destructive intraoperative histopathology is introduced with the first PA clinical trials according to the diagnostic grades of thick cancer specimens, demonstrating the multi‐feature analysis using a supervised learning algorithm. This approach has the potential for pathologists to differentiate suspicious cancer region accurately, which can be linked to subsequent postoperative examination.
(
) can alleviate diet-induced obesity in animal models, and phlorotannins contained in
help prevent hypertrophy-induced adipocyte differentiation. Receptor for advanced glycation end-products (RAGE) ...is well known to induce hypertrophy of visceral fat and to trigger inflammation substantially. While the relationship between RAGE and obesity and inflammation has been well-characterized, few studies describe the effects of phlorotannin on RAGE. In this study, we investigated the anti-obesity effects of pyrogallol-phloroglucinol-6,6-bieckol (PPB)-a single compound from the ethanoic extract of
-mediated by a reduction in the inflammation caused by RAGE and RAGE ligands. In visceral fat, PPB (i) significantly inhibited RAGE ligands, (ii) reduced the expression of RAGE, and (iii) reduced the binding ratio between RAGE and RAGE ligands. Under lower expression of RAGE, RAGE ligands and their cognate binding, the differentiation of macrophages found in visceral fat into M1-type-the pro-inflammatory form of this immune cell-was reduced. As the M1-type macrophage decreased, pro-inflammatory cytokines, which cause obesity, decreased in visceral fat. The results of this study highlight the anti-obesity effects of PPB, with the effects mediated by reductions in RAGE, RAGE ligands, and inflammation.
The use of light to facilitate copper-catalyzed cross-couplings of nitrogen nucleophiles can enable C–N bond formation to occur under unusually mild conditions. In this study, we substantially expand ...the scope of such processes, establishing that this approach is not limited to reactions of carbazoles with iodobenzene and alkyl halides. Specifically, we demonstrate for the first time that other nitrogen nucleophiles (e.g., common pharmacophores such as indoles, benzimidazoles, and imidazoles) as well as other electrophiles (e.g., hindered/deactivated/heterocyclic aryl iodides, an aryl bromide, an activated aryl chloride, alkenyl halides, and an alkynyl bromide) serve as suitable partners. Photoinduced C–N bond formation can be achieved at room temperature using a common procedure with an inexpensive catalyst (CuI) that does not require a ligand coadditive and is tolerant of moisture and a variety of functional groups.
Hypertension induces renal fibrosis or tubular interstitial fibrosis, which eventually results in end-stage renal disease. Epithelial-to-mesenchymal transition (EMT) is one of the underlying ...mechanisms of renal fibrosis. Though previous studies showed that Ecklonia cava extracts (ECE) and dieckol (DK) had inhibitory action on angiotensin (Ang) I-converting enzyme, which converts Ang I to Ang II. It is known that Ang II is involved in renal fibrosis; however, it was not evaluated whether ECE or DK attenuated hypertensive nephropathy by decreasing EMT. In this study, the effect of ECE and DK on decreasing Ang II and its down signal pathway of angiotensin type 1 receptor (AT1R)/
/
, which is related with the EMT and restoring renal function in spontaneously hypertensive rats (SHRs), was investigated. Either ECE or DK significantly decreased the serum level of Ang II in the SHRs. Moreover, the renal expression of AT1R/
/
was decreased by the administration of either ECE or DK. The mesenchymal cell markers in the kidney of SHRs was significantly decreased by ECE or DK. The fibrotic tissue of the kidney of SHRs was also significantly decreased by ECE or DK. The ratio of urine albumin/creatinine of SHRs was significantly decreased by ECE or DK. Overall, the results of this study indicate that ECE and DK decreased the serum levels of Ang II and expression of AT1R/
/
, and then decreased the EMT and renal fibrosis in SHRs. Furthermore, the decrease in EMT and renal fibrosis could lead to the restoration of renal function. It seems that ECE or DK could be beneficial for decreasing hypertensive nephropathy by decreasing EMT and renal fibrosis.
Background and Objectives: Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to control pain and fever. However, their effect on COVID-19 infected patients has not been fully studied. ...In this study, we investigated the effect of the duration of NSAIDs use on COVID-19 infection and clinical outcomes. Materials and Methods: In South Korea, 25,739 eligible patients who received COVID-19 testing between 1 January and 31 July 2020, were included in this retrospective observational cohort analysis. Based on the date of the first COVID-19 test for each patient, NSAID prescription dates were used to separate patients into two groups (short-term group: <2 weeks; long-term group: 8−12 weeks). COVID-19 infectivity and clinical outcomes were analyzed. We used the propensity score-matching (PSM) method. Results: Of the 580 patients who had taken NSAIDs before the date of COVID-19 test, 534 and 46 patients were grouped in the short- and long-term NSAID-use groups, respectively. We did not find a statistically significant increased risk of COVID-19 infection (adjustment for age and sex, p = 0.413; adjustment for age, sex, region of residence, comorbidity, Charlson Comorbidity Index, and current use of medication, p = 0.259) or change in clinical outcomes, including conventional oxygen therapy, admission of intensive care unit, artificial ventilation, or death, between the two groups in which the PSM method was applied. Conclusions: The duration of NSAIDs use did not have a statistically significant effect on COVID-19 infectivity or clinical outcomes. However, further studies looking at clinical presentation and laboratory test results in a large number of people should be performed.
Abstract
Background
This study aimed to discover the most stable outcome among different Kirschner-wire (K-wire) configurations for fixation of a lateral condyle fracture (Milch type II) in different ...loads of stress by using finite element analyses (FEA).
Methods
The right humerus of a 6-year-old boy with a lateral condyle fracture (Milch type II), was modelled with a computer aided engineering. Using FEA, peak von Mises stress and stiffness were evaluated first for a single K-wire fixation by varying the angle (0, 5, 10, 15, 20, 25, 30 degrees). Then, based on the single K-wire result, assessment of peak von Mises stress and stiffness were evaluated via FEA for two- or three-wire fixation under various configurations (two convergent, two parallel, three divergent).
Results
Single K-wire fixation by 5 and 25 degrees had the lowest peak von Mises stress. The fracture site showed higher stiffness at 0, 5 and 15 degrees. Considering the collected results and clinical situation, 5 degree K-wire was selected for the FEA of multiple K-wire fixation. For multiple K-wire fixation, three divergent (5–20-35 degrees) K-wires showed better stability, both in peak von Mises stress and stiffness, than any two-K-wire configurations. Among two K-wire fixations, two divergent (5–50 degrees) K-wires provided the lowest von Mises stress in varus and valgus while two divergent (5–65 degrees) K-wires showed better results in flexion, extension, internal and external rotation, and both configurations showed similar results in stiffness.
Conclusions
We successfully created a paediatric lateral condyle fracture (Milch type II) model which was used to conduct FEA on different K-wire configurations to achieve stability of the fracture. Our results show that an initial K-wire inserted at 5 degrees, followed by the insertion of a second divergent wire at either 45 or 60 degrees provides the most stability in two K-wire fixations in this type of fracture repair.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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