The axially chiral tetra-ortho-substituted biaryl skeleton exists in numerous biologically important natural products, pharmaceutical molecules, chiral catalysts, and ligands. The efficient synthesis ...of chiral tetra-ortho-substituted biaryl structures remains a challenging but unsolved problem. Among various asymmetric synthetic protocols, enantioselective Suzuki-Miyaura cross-coupling represents one of the most straightforward and versatile approaches. Herein we describe a powerful Suzuki-Miyaura coupling enabled by a P-chiral monophosphorus ligand BaryPhos, providing a broad range of synthetically challenging chiral tetra-ortho-substituted biaryls in excellent enantioselectivities and yields. In addition to the enhanced reactivity for sterically hindered cross-coupling, the rational design of BaryPhos also enabled a new catalysis mode of asymmetric cross-coupling involving noncovalent interactions between the ligand and two coupling partners to effect efficient stereoinduction. This protocol is robust and practical, allowing for a concise enantioselective synthesis of therapeutically valuable male contraceptive and antitumor agent gossypol.
An efficient and general method for the synthesis of difluoroalkylated phenanthridine derivatives through palladium-catalyzed reaction of difluoroalkyl bromides with isocyanides is described. The ...reaction can also be extended to perfluoroalkyl iodides. Mechanistic studies reveal that a difluoroalkyl radical via a single-electron-transfer pathway is involved in the reaction.
It is well established that ferroptosis is primarily induced by peroxidation of long-chain poly-unsaturated fatty acid (PUFA) through nonenzymatic oxidation by free radicals or enzymatic stimulation ...of lipoxygenase. Although there is emerging evidence that long-chain saturated fatty acid (SFA) might be implicated in ferroptosis, it remains unclear whether and how SFA participates in the process of ferroptosis. Using endogenous metabolites and genome-wide CRISPR screening, we have identified FAR1 as a critical factor for SFA-mediated ferroptosis. FAR1 catalyzes the reduction of C16 or C18 saturated fatty acid to fatty alcohol, which is required for the synthesis of alkyl-ether lipids and plasmalogens. Inactivation of FAR1 diminishes SFA-dependent ferroptosis. Furthermore, FAR1-mediated ferroptosis is dependent on peroxisome-driven ether phospholipid biosynthesis. Strikingly, TMEM189, a newly identified gene which introduces vinyl-ether double bond into alkyl-ether lipids to generate plasmalogens abrogates FAR1-alkyl-ether lipids axis induced ferroptosis. Our study reveals a new FAR1-ether lipids-TMEM189 axis dependent ferroptosis pathway and suggests TMEM189 as a promising druggable target for anticancer therapy.
An efficient palladium‐catalyzed Heck‐type reaction of fluoroalkyl halides, including perfluoroalkyl bromides, trifluoromethyl iodides, and difluoroalkyl bromides, has been developed. The reaction ...proceeds under mild reaction conditions with high efficiency and broad substrate scope, and provides a general and straightforward access to fluoroalkylated alkenes which are of interest in life and material sciences.
Simplicity is beauty: The title reaction features a broad substrate scope and excellent functional‐group compatibility. Mechanistic studies reveal that the free fluoroalkyl radicals initiated by Pd0Ln through a single‐electron transfer pathway is involved in the Heck‐type catalytic cycle.
Pristine metal-organic frameworks (MOFs) have received much attention in recent years due to their high specific surface areas, large porosity, excellent pore size distributions, flexible structure, ...and remarkable catalytic properties. The design of functional MOFs that can function as efficient HER and OER catalysts is significant in solving the energy crisis but remains a big challenge. Tri-metallic metal-organic frameworks show a good application prospect in water oxidation. In this review, we are going to focus on the latest progress and future trends in the development of pristine trimetallic MOFs with respect to the OER. The synergistic effect between multi-metal active sites is effective at improving the intrinsic activity of MOFs toward the OER. By summarizing the synthesis method of tri-metallic MOFs and observing their performance toward the oxygen evolution reaction, we hope that this review will trigger new developments in coordination chemistry, electrochemistry, nanomaterials and energy materials.
This minireview summarizes the synthesis strategies to access trimetallic MOFs and their catalytic performances toward the oxygen evolution reaction.
To unlock the potential of flexible resources, a multi-time-scale economic scheduling strategy for the virtual power plant (VPP) to participate in the wholesale energy and reserve market considering ...large quantity of deferrable loads (DLs) aggregation and disaggregation is proposed in this paper. For the VPP multi-time-scale scheduling including day-ahead bidding and real-time operation, the following models are proposed, namely, DLs aggregation model based on clustering approach, economic scheduling model considering DLs aggregation, and DLs disaggregation model satisfying consumers' requirements, respectively. The proposed strategy can realize the efficient management of massive DLs to reduce the energy management complexity and increase the overall economics with high computation efficiency, which indicate its promising application in the VPP economic scheduling.
Current guidelines recommend surgical resection as the first-line option for patients with solitary hepatocellular carcinoma (HCC); unfortunately, postoperative recurrence rate remains high and there ...is no reliable prediction tool. We explored the potential of radiomics coupled with machine-learning algorithms to improve the predictive accuracy for HCC recurrence.
A total of 470 patients who underwent contrast-enhanced CT and curative resection for solitary HCC were recruited from 3 independent institutions. In the training phase of 210 patients from Institution 1, a radiomics-derived signature was generated based on 3384 engineered features extracted from primary tumor and its periphery using aggregated machine-learning framework. We employed Cox modeling to build predictive models. The models were then validated using an internal dataset of 107 patients and an external dataset of 153 patients from Institution 2 and 3.
Using the machine-learning framework, we identified a three-feature signature that demonstrated favorable prediction of HCC recurrence across all datasets, with C-index of 0.633–0.699. Serum alpha-fetoprotein, albumin-bilirubin grade, liver cirrhosis, tumor margin, and radiomics signature were selected for preoperative model; postoperative model incorporated satellite nodules into above-mentioned predictors. The two models showed superior prognostic performance, with C-index of 0.733–0.801 and integrated Brier score of 0.147–0.165, compared with rival models without radiomics and widely used staging systems (all P < 0.05); they also gave three risk strata for recurrence with distinct recurrence patterns.
When integrated with clinical data sources, our three-feature radiomics signature promises to accurately predict individual recurrence risk that may facilitate personalized HCC management.
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•We identified a three-feature fusion signature using machine-learning framework.•The signature coupled with clinical sources accurately predicted HCC recurrence.•This signature may serve as an early detector of aggressive disease.•We highlight the complementary nature of radiomics and existing variables.
Objectives
This study was conducted in order to establish and validate a radiomics model for predicting lymph node (LN) metastasis of intrahepatic cholangiocarcinoma (IHC) and to determine its ...prognostic value.
Methods
For this retrospective study, a radiomics model was developed in a primary cohort of 103 IHC patients who underwent curative-intent resection and lymphadenectomy. Radiomics features were extracted from arterial phase computed tomography (CT) scans. A radiomics signature was built based on highly reproducible features using the least absolute shrinkage and selection operator (LASSO) method. Multivariate logistic regression analysis was adopted to establish a radiomics model incorporating radiomics signature and other independent predictors. Model performance was determined by its discrimination, calibration, and clinical usefulness. The model was internally validated in 52 consecutive patients.
Results
The radiomics signature comprised eight LN-status–related features and showed significant association with LN metastasis in both cohorts (
p
< 0.001). A radiomics nomogram that incorporates radiomics signature and CA 19-9 level showed good calibration and discrimination in the primary cohort (AUC 0.8462) and validation cohort (AUC 0.8921). Promisingly, the radiomics nomogram yielded an AUC of 0.9224 in the CT-reported LN-negative subgroup. Decision curve analysis confirmed the clinical utility of this nomogram. High risk for metastasis portended significantly lower overall and recurrence-free survival than low risk for metastasis (both
p
< 0.001). The radiomics nomogram was an independent preoperative predictor of overall and recurrence-free survival.
Conclusions
Our radiomics model provided a robust diagnostic tool for prediction of LN metastasis, especially in CT-reported LN-negative IHC patients, that may facilitate clinical decision-making.
Key Points
• The radiomics nomogram showed good performance for prediction of LN metastasis in IHC patients, particularly in the CT-reported LN-negative subgroup.
• Prognosis of high-risk patients remains dismal after curative-intent resection.
• The radiomics model may facilitate clinical decision-making and define patient subsets benefiting most from surgery.
Abstract
Outflows are inevitably driven from the disk if the vertical component of the black hole (BH) gravity cannot resist the radiation force. We derive the mass-loss rate in the outflows by ...solving a dynamical equation for the vertical gas motion in the disk. The structure of a supercritical accretion disk is calculated with the radial energy advection included. We find that most inflowing gas is driven into outflows if the disk is accreting at a moderate Eddington-scaled rate (up to ∼100) at its outer edge, i.e., only a small fraction of gas is accreted by the BH, which is radiating at several Eddington luminosities, while it reaches around ten for extremely high accretion rate cases (
m
̇
≡
M
̇
/
M
̇
Edd
∼
1000
). Compared with a normal slim disk, the disk luminosity is substantially suppressed due to the mass loss in the outflows. We apply the model to the light curves of the tidal disruption events (TDEs) and find that the disk luminosity declines very slowly with time even if a typical accretion rate
m
̇
∝
t
−
5
/
3
is assumed at the outer edge of the disk, which is qualitatively consistent with the observed light curves in some TDEs and helps us to understand the energy deficient phenomenon observed in the TDEs. Strong outflows from supercritical accretion disks surrounding supermassive BHs may play crucial roles in their host galaxies, which can be taken as an ingredient in the mechanical feedback models. The implications of the results on the growth of supermassive BHs are also discussed.
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