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Simple and commercially available magnesium halides catalyzed the hydroboration of various isocyanates and ketones.

A highly tunable defluorophosphorylation of fluorinated peroxides for the preparation of C3,4-diphosphoryl furans and C4-monophosphoryl furans under conditions with no added transition metals is disclosed.

The emerging potassium-ion batteries (PIBs) have been placing stratospheric expectations for realizing grid-scale electrochemical storage of renewable energy. However, the unsatisfactory K-storage of PIB anode materials, especially promising carbonaceous materials, significantly limited the development of PIBs. Here, a molecular design strategy was proposed to realize controllable structure transformation of soft carbon (SC) materials for enhanced K-storage performance. The optimized SC-PCN material delivered a high reversible K-storage capacity of 838 mAh/g at 50 mA/g, outstanding rate capability (213 mAh/g at 1000 mA/g), and excellent long-term cycling performance (301 mAh/g maintained after 300 cycles at 500 mA/g), superior to most previously reported carbon-based PIB anodes materials. Reaction kinetic analysis revealed that the proposed molecular design strategy can achieve the transformation from a surface capacitive-dominated mechanism to a capacitive-diffusion hybrid mechanism for SC-PCN, benefiting from its unique microstructures with highly defective surface generated via the synergistic effect from template removal, N doping, and surface reconstruction. The optimal hybrid K-storage mechanism should be responsible for the excellent K-storage properties of the prepared SC-PCN.

The direct cross-couplings of diaryl sulfoxides with aryl bromides via C-S bond cleavage could be readily accomplished using nickel(II) as the catalyst, 1,2-bis(diphenylphosphino)ethane (dppe) as the ligand, and magnesium turnings as the reducing metal in THF, leading to the corresponding biaryls in moderate to good yields. The reaction exhibited a broad substrate scope and could be applied to a gram-scale synthesis. The "one-pot" reaction, which avoids the utility of presynthesized and moisture-labile organometallic compounds, is operationally simple and step-economic.

The efficient palladium-catalyzed synthesis of esters from readily available arenes has been developed. These C-H bond esterifications were achieved relying on the regioselective thianthrenation to generate the aryl-TT salts, which were treated as reactive electrophilic substrates to couple with phenol formate and

Oncogenic stress induces DNA damage repair (DDR) that permits escape from mitotic catastrophe and allows early precursor lesions during the evolution of cancer. SAMHD1, a dNTPase protecting cells from viral infections, has been recently found to participate in DNA damage repair process. However, its role in tumorigenesis remains largely unknown. Here, we show that SAMHD1 is up-regulated in early-stage human carcinoma tissues and cell lines under oxidative stress or genotoxic insults. We further demonstrate that de-ubiquitinating enzyme USP7 interacts with SAMHD1 and de-ubiquitinates it at lysine 421, thus stabilizing SAMHD1 protein expression for further interaction with CtIP for DDR, which promotes tumor cell survival under genotoxic stress. Furthermore, SAMHD1 levels positively correlates with USP7 in various human carcinomas, and is associated with an unfavorable survival outcome in patients who underwent chemotherapy. Moreover, USP7 inhibitor sensitizes tumor cells to chemotherapeutic agents by decreasing SAMHD1 in vitro and in vivo. These findings suggest that de-ubiquitination of SAMHD1 by USP7 promotes DDR to overcome oncogenic stress and affect chemotherapy sensitivity.

Diverse 2,3-substituted indanones are accessed in an efficient and robust protocol by a rhodium-catalyzed tandem carborhodium/cyclization and intramolecular proton shift pathway. The reaction is compatible with a broad range of functional internal acetylenes, especially for natural and functionalized alkynes derivatives, affording the desired indanones in good to excellent yields. Remarkably, this reaction features very mild and sustainable conditions using water as the sole solvent and without exogenous ligands. Control studies support that indanone is formed through the intramolecular proton transfer process from the key intermediate indenol.

We report a general, scalable, and convenient photochemical process for diversities of distal oxygenated nitriles from corresponding less-strained ketoxime esters allowing one-step introductions of ether and cyano groups, which avoids the utilization of toxic cyanide reagents. A wide range of ketoxime esters involving five-membered to eight-membered cycloketoxime esters and linear ketoxime esters participate smoothly under operately simple and mild conditions, affording structurally variable ring-opening products.

An unprecedented four-component defluorinative reaction of allylic fluorides, amidines, and Cs2CO3 for the convenient synthesis of valuable pyrimidine-containing amidino carbamates under transition-metal-free conditions was developed.

A green and sustainable electrochemical hydroboration of carbonyl compounds with HBpin has been reported for the first time. Under catalyst-free and additive-free mild reaction conditions the corresponding boronic esters were obtained in excellent yields

A copper-catalysed three-component reaction utilizing readily available feedstocks was investigated, providing an operationally simple and practical route to trifluoromethyl allenes under mild and environmentally friendly conditions.

A practical and convenient approach that enabled radical-mediated conjugate addition of unreactive alkenes to electron-deficient alkenes leading to a broad range of substituted malononitriles was disclosed.

An efficient defluorinative net-[3 + 3]-cyclization strategy for the construction of perfluoroalkyl-substituted pyrimidine derivatives by using a series of perfluoroalkyl alkynes and amidines as starting materials was developed. The present reaction proceeded successfully under transition-metal-free conditions to form two new C–N bonds and a new heterocyclic ring through a sequence of hydroamination, defluorination, and annulation. The desired pyrimidines could be obtained with good functional group tolerance and moderate to good yields. Moreover, the distinctive fluorine effects of perfluoroalkyl substituents are vital for tuning the reactivity of alkynes for the anticipated defluorinative annulation. The pendant π system would lower associated bond dissociation energy significantly compared to that of a nonactivated C(sp3)–F bond.

An efficient transition-metal-free hydrodefluorination reaction of trifluoromethyl alkenes for accessing gem-difluoroalkenes is developed. It was surprising to find that the phosphoryl anion is able to mediate the defluorination.

The simple, commercially available ZnBr2 has been successfully employed as a highly efficient and chemoselective catalyst for the dehydrogenative borylation of terminal alkynes with HBpin under mild conditions. It shows a good tolerance toward various functional groups such as aryl, alkyl, heteroaryl, etc. The plausible reaction mechanism has been investigated based on the corresponding stoichiometric experiments and DFT calculations.

Progerin, a product of LMNA mutation, leads to multiple nuclear abnormalities in patients with Hutchinson-Gilford progeria syndrome (HGPS), a devastating premature aging disorder. Progerin also accumulates during physiological aging. Here, we demonstrate that impaired insulin-like growth factor 1 receptor (IGF-1R)/Akt signaling pathway results in severe growth retardation and premature aging in Zmpste24 −/− mice, a mouse model of progeria. Mechanistically, progerin mislocalizes outside of the nucleus, interacts with the IGF-1R, and down-regulates its expression, leading to inhibited mitochondrial respiration, retarded cell growth, and accelerated cellular senescence. Pharmacological treatment with the PTEN (phosphatase and tensin homolog deleted on chromosome 10) inhibitor bpV (HOpic) increases Akt activity and improves multiple abnormalities in Zmpste24-deficient mice. These findings provide previously unidentified insights into the role of progerin in regulating the IGF-1R/Akt signaling in HGPS and might be useful for treating LMNA -associated progeroid disorders.

An efficient Sonogashira coupling of a heterocyclic phosphonium salt with a terminal alkyne via C-P bond cleavage was developed. The reactions proceeded smoothly in the presence of palladium catalyst, copper(I) iodide, and

Functional molecules bearing polychlorinated moieties usually play versatile roles in organic synthesis and biochemistry. A copper-catalyzed multicomponent polychloro-carboalkynylation of alkenes presents an efficient and operationally simple approach for the synthesis of β-polychlorinated alkynes. Mechanistic experiments were conducted demonstrating that an

Correction for ‘Copper-catalysed synthesis of trifluoromethyl allenes via fluoro-carboalkynylation of alkenes’ by Mengning Wang et al., Org. Chem. Front., 2022, 9, 1844–1849, https://doi.org/10.1039/D1QO01823J.

The simple, commercially available ZnBr

A titanium(IV)-mediated ring-opening/dehydroxylative cross-coupling of diaryl-substituted methanols with a cyclopropanol derivative was developed. The reactions proceeded efficiently to provide synthetically useful γ,γ-diaryl esters in moderate to good yields, which could be applied to the functionalization of complex molecules derived from bioactive fenofibrate and isoxepac and the synthesis of a precursor of Zoloft.

The clinical treatment of chronic postoperative pain (CPSP) remains challenging. The side effects of chronic morphine treatment limit its clinical application. MEL-0614, a novel endomorphin analogue that is highly selective and agonistic for μ opioid receptor (MOR), produces a more powerful analgesic effect than that of morphine. In this study, we explored the difference in antinociceptive tolerance and related mechanisms between MEL-0614 and morphine in CPSP induced in a skin/muscle incision and retraction (SMIR) mice model. We found that acute administration of MEL-0614 (1, 3, 5, and 10 nmol, i.t.) produced a dose-dependent analgesic effect that was superior to that of morphine in the SMIR mice model. Long-term MEL-0614 treatment (10 nmol, i.t.) did not induce tolerance compared with morphine. Notably, tolerance induced by morphine could be greatly prevented and/or inhibited via cross-administration or coadministration between MEL-0614 and morphine. In addition, MEL-0614 accelerated the recovery of postoperative pain, whereas morphine aggravated postoperative pain and prolonged its recovery time regardless of preoperative or postoperative treatment. In addition, MEL-0614 did not activate microglia and the P2X7R signaling pathway and showed reduced expression iba1 and P2X7R compared with that observed after morphine administration. Release of inflammatory factors was induced by continued administration of morphine during SMIR surgery, but MEL-0614 did not promote the activation of inflammatory factors. Our results showed that MEL-0614 has superior analgesic effects in CPSP and leads to tolerance to a lesser degree than morphine. Further, MEL-0614 may be used as a promising treatment option for the long-term treatment in CPSP.

Aging is a primary risk factor for neurodegenerative diseases, such as Alzheimer's disease (AD). SIRT2, an NAD

Tumor metastasis is a complex and multistep process and its exact molecular mechanisms remain unclear. We attempted to find novel microRNAs (miRNAs) contributing to the migration and invasion of breast cancer cells. In this study, we found that the expression of miR-487a was higher in MDA-MB-231breast cancer cells with high metastasis ability than MCF-7 breast cancer cells with low metastasis ability and the treatment with transforming growth factor β1 (TGF-β1) significantly increased the expression of miR-487a in MCF-7 and MDA-MB-231 breast cancer cells. Subsequently, we found that the transfection of miR-487a inhibitor significantly decreased the expression of vimentin, a mesenchymal marker, while increased the expression of E-cadherin, an epithelial marker, in both MCF-7 cells and MDA-MB-231 cells. Also, the inactivation of miR-487a inhibited the migration and invasion of breast cancer cells. Furthermore, our findings demonstrated that miR-487a directly targeted the MAGI2 involved in the stability of PTEN. The down-regulation of miR-487a increased the expression of p-PTEN and PTEN, and reduced the expression of p-AKT in both cell lines. In addition, the results showed that NF-kappaB (p65) significantly increased the miR-487a promoter activity and expression, and TGF-β1 induced the increased miR-487a promoter activity via p65 in MCF-7 cells and MDA-MB-231 cells. Moreover, we further confirmed the expression of miR-487a was positively correlated with the lymph nodes metastasis and negatively correlated with the expression of MAGI2 in human breast cancer tissues. Overall, our results suggested that miR-487a could promote the TGF-β1-induced EMT, the migration and invasion of breast cancer cells by directly targeting MAGI2.

A new honeycomb-like 2D Metal-organic polyhedral framework, {Cu3.75(BrCPEIP)2.5·(H2O)2.75·DMF}n (NJFU-5, H3BrCPEIP ​= ​5-((3-bromo-5-carboxyphenyl)ethynyl)isophthalic acid) was solvothermally synthesized and structurally characterized, which shows a BET surface area of 473 ​m2 ​g−1. Meanwhile, NJFU exhibits a comparably higher CO2 adsorption capacity of 37.0 ​cm3 ​g-1 (4.6 ​wt%) at 1 ​bar and 298 ​K in 2D MOF family, and a high CO2 selective adsorption toward N2 and CH4 as well.