A new series of spiro‐bicyclic bisborane catalysts has been prepared by means of hydroboration reactions of C2‐symmetric spiro‐bicyclic dienes with HB(C6F5)2 and HB(p‐C6F4H)2. When used for ...hydrogenation of quinolines, these catalysts give excellent yields and enantiomeric excesses, and show turnover numbers of up to 460. The most attractive feature of these metal‐free hydrogenation reactions was the broad functional‐group tolerance, making this method complementary to existing methods for quinoline hydrogenation.
B,B bicycles: A series of C2‐symmetric spiro‐bicyclic bisboranes has been prepared. These bisboranes demonstrate highly effective and selective asymmetric hydrogenation of quinolines. The exceedingly broad functional‐group tolerance allows access to various enantioenriched and functionalized tetrahydroquinilines, which are inaccessible by previous methods using either borane or transition‐metal catalysts.
Current pharmaceutical research and development (R&D) is a high-risk investment which is usually faced with some unexpected even disastrous failures in different stages of drug discovery. One main ...reason for R&D failures is the efficacy and safety deficiencies which are related largely to absorption, distribution, metabolism and excretion (ADME) properties and various toxicities (T). Therefore, rapid ADMET evaluation is urgently needed to minimize failures in the drug discovery process. Here, we developed a web-based platform called ADMETlab for systematic ADMET evaluation of chemicals based on a comprehensively collected ADMET database consisting of 288,967 entries. Four function modules in the platform enable users to conveniently perform six types of drug-likeness analysis (five rules and one prediction model), 31 ADMET endpoints prediction (basic property: 3, absorption: 6, distribution: 3, metabolism: 10, elimination: 2, toxicity: 7), systematic evaluation and database/similarity searching. We believe that this web platform will hopefully facilitate the drug discovery process by enabling early drug-likeness evaluation, rapid ADMET virtual screening or filtering and prioritization of chemical structures. The ADMETlab web platform is designed based on the Django framework in Python, and is freely accessible at
http://admet.scbdd.com/
.
To our knowledge, no randomised study has compared postmastectomy hypofractionated radiotherapy with conventional fractionated radiotherapy in patients with breast cancer. This study aimed to ...determine whether a 3-week schedule of postmastectomy hypofractionated radiotherapy is as efficacious and safe as a 5-week schedule of conventional fractionated radiotherapy.
This randomised, non-inferiority, open-label, phase 3 study was done in a single academic hospital in China. Patients aged 18–75 years who had undergone mastectomy and had at least four positive axillary lymph nodes or primary tumour stage T3–4 disease were eligible to participate. Patients were randomly assigned (1:1) according to a computer-generated central randomisation schedule, without stratification, to receive chest wall and nodal irradiation at a dose of 50 Gy in 25 fractions over 5 weeks (conventional fractionated radiotherapy) or 43·5 Gy in 15 fractions over 3 weeks (hypofractionated radiotherapy). The modified intention-to-treat population (including all eligible patients who underwent randomisation but excluding those who were considered ineligible or withdrew consent after randomisation) was used in primary and safety analyses. The primary endpoint was 5-year locoregional recurrence, and a 5% margin was used to establish non-inferiority (equivalent to a hazard ratio <1·883). This trial is registered at ClinicalTrials.gov, number NCT00793962.
Between June 12, 2008, and June 16, 2016, 820 patients were enrolled and randomly assigned to the conventional fractionated radiotherapy group (n=414) or hypofractionated radiotherapy group (n=406). 409 participants in the conventional fractionated radiotherapy group and 401 participants in the hypofractionated radiotherapy group were included in the modified intention-to-treat analyses. At a median follow-up of 58·5 months (IQR 39·2–81·8), 60 (7%) patients had developed locoregional recurrence (31 patients in the hypofractionated radiotherapy group and 29 in the conventional fractionated radiotherapy group); the 5-year cumulative incidence of locoregional recurrence was 8·3% (90% CI 5·8–10·7) in the hypofractionated radiotherapy group and 8·1% (90% CI 5·4–10·6) in the conventional fractionated radiotherapy group (absolute difference 0·2%, 90% CI −3·0 to 2·6; hazard ratio 1·10, 90% CI 0·72 to 1·69; p<0·0001 for non-inferiority). There were no significant differences between the groups in acute and late toxicities, except that fewer patients in the hypofractionated radiotherapy group had grade 3 acute skin toxicity than in the conventional fractionated radiotherapy group (14 3% of 401 patients vs 32 8% of 409 patients; p<0·0001).
Postmastectomy hypofractionated radiotherapy was non-inferior to and had similar toxicities to conventional fractionated radiotherapy in patients with high-risk breast cancer. Hypofractionated radiotherapy could provide more convenient treatment and allow providers to treat more patients.
National Key Projects of Research and Development of China; the Chinese Academy of Medical Science Innovation Fund for Medical Sciences; and Beijing Marathon of Hope, Cancer Foundation of China.
Superlattice materials offer new opportunities to modify optical and electrical properties of recently emerging 2D materials. The insertion of tetraethylbenzidine (EtDAB) into interlamination of the ...established 2D PbI2 semiconductor through a mild solution method yielded the first lead iodide superlattice, EtDAB⋅4PbI2 (EtDAB=tetraethylbenzidine), with radical and non‐radical forms. The non‐radical form has a non‐ionic structure that differs from the common ionic structures for inorganic–organic hybrid lead halides. The radical form shows five orders of magnitude greater conductance and broader photoconductive response range (UV/Vis → UV/Vis‐IR), than pure PbI2 and the non‐radical form of the superlattice.
Lead the way: The first lead‐iodide superlattice constructed from non‐ionic organic molecules and PbI2 through van der Waals interactions is a new type of inorganic–organic hybrid and has a radical and a non‐radical form. The radical form has an almost five orders of magnitude greater conductivity and broader band photoconductive response than that of the non‐radical form or pure PbI2.
Polyimide (PI) aerogels have attracted great attention owing to their low density and excellent thermal stability. However, hydrophobic surface modification is required for PI aerogels to improve ...their ability in oil/water separation due to their amphiphilic characteristic. Two-dimensional MXenes (transition metal carbides/nitrides) can be utilized as nanofillers to enhance the properties of polymers because of their unique layered structure and versatile interface chemistry. Herein, the robust, lightweight, and hydrophobic PI/MXene three-dimensional architectures were fabricated via freeze-drying of polyamide acid/MXene suspensions and thermal imidization. Polyamide acid was synthesized using N-N-dimethylacetamide and 4,4′-oxydianiline. MXene (Ti3C2T x ) dispersion was obtained via the etching of Ti3AlC2 and ultrasonic exfoliation. Taking advantage of the strong interaction between PI chains and MXene nanosheets, the interconnected, highly porous, and hydrophobic PI/MXene aerogels with low density were fabricated, resulting in the improved compressive performance, remarkable oil absorption capacity, and efficient separation of oil and water. For the PI/MXene-3 aerogel (weight ratio, 5.2:1) without any surface modification, the water contact angle was 119° with a density of 23 mg/cm3. This aerogel can completely recover to its original height after 50 compression–release cycles, exhibiting superelasticity and exceptional fatigue-resistant ability. It also showed high absorption capacities to various organic liquids ranging from approximately 18 to 58 times of their own weight. This hybrid aerogel can rapidly separate the chloroform, soybean oil, and liquid paraffin from the water–oil system. The thermally stable hybrid aerogel also exhibited excellent fire safety properties and outstanding reusability under an extreme environment.
Abstract
Most triple-negative breast cancer (TNBC) patients fail to respond to T cell-mediated immunotherapies. Unfortunately, the molecular determinants are still poorly understood. Breast cancer is ...the disease genetically linked to a deficiency in autophagy. Here, we show that autophagy defects in TNBC cells inhibit T cell-mediated tumour killing in vitro and in vivo. Mechanistically, we identify Tenascin-C as a candidate for autophagy deficiency-mediated immunosuppression, in which Tenascin-C is Lys63-ubiquitinated by Skp2, particularly at Lys942 and Lys1882, thus promoting its recognition by p62 and leading to its selective autophagic degradation. High Tenascin-C expression is associated with poor prognosis and inversely correlated with LC3B expression and CD8
+
T cells in TNBC patients. More importantly, inhibition of Tenascin-C in autophagy-impaired TNBC cells sensitizes T cell-mediated tumour killing and improves antitumour effects of single anti-PD1/PDL1 therapy. Our results provide a potential strategy for targeting TNBC with the combination of Tenascin-C blockade and immune checkpoint inhibitors.
Catalytic amounts of B(C6F5)3 have been found to be able to promote the intramolecular cyclization of vinyl-substituted N,N-dialkyl arylamines to afford nitrogen-containing heterocycles. Our ...mechanistic studies indicate the reaction is initiated by abstraction of an α-hydride from an N-alkyl substituent by B(C6F5)3, which is followed by cyclization, and is concluded by delivery of the hydride to the cyclic cationic intermediate. The dual roles of B(C6F5)3, first as an oxidant and then as a hydride-carrying reductant, have enabled a rare redox-neutral cyclization process between a sp3 carbon and an electron-rich olefin without using a transition metal or an external oxidant.
Purpose
Microvascular invasion (MVI) is a valuable predictor of survival in hepatocellular carcinoma (HCC) patients. This study developed predictive models using eXtreme Gradient Boosting (XGBoost) ...and deep learning based on CT images to predict MVI preoperatively.
Methods
In total, 405 patients were included. A total of 7302 radiomic features and 17 radiological features were extracted by a radiomics feature extraction package and radiologists, respectively. We developed a XGBoost model based on radiomics features, radiological features and clinical variables and a three-dimensional convolutional neural network (3D-CNN) to predict MVI status. Next, we compared the efficacy of the two models.
Results
Of the 405 patients, 220 (54.3%) were MVI positive, and 185 (45.7%) were MVI negative. The areas under the receiver operating characteristic curves (AUROCs) of the Radiomics-Radiological-Clinical (RRC) Model and 3D-CNN Model in the training set were 0.952 (95% confidence interval (CI) 0.923–0.973) and 0.980 (95% CI 0.959–0.993), respectively (
p
= 0.14). The AUROCs of the RRC Model and 3D-CNN Model in the validation set were 0.887 (95% CI 0.797–0.947) and 0.906 (95% CI 0.821–0.960), respectively (
p
= 0.83). Based on the MVI status predicted by the RRC and 3D-CNN Models, the mean recurrence-free survival (RFS) was significantly better in the predicted MVI-negative group than that in the predicted MVI-positive group (RRC Model: 69.95 vs. 24.80 months,
p
< 0.001; 3D-CNN Model: 64.06 vs. 31.05 months,
p
= 0.027).
Conclusion
The RRC Model and 3D-CNN models showed considerable efficacy in identifying MVI preoperatively. These machine learning models may facilitate decision-making in HCC treatment but requires further validation.
A series of 2D isomorphous MOFs M (HBTC)(BMIOPE)·DMF·H2On (M = Zn (1), Zn0.7Co0.3 (2), Zn0.5Co0.5 (3), Zn0.3Co0.7 (4), Co (5), H3BTC = 1,3,5‐benzenetricarboxylic acid, BMIOPE = ...4,4′‐bis(2‐methylimidazol‐1‐yl)diphenyl ether) were synthesized to investigate the correction between the center metal ions and the photocatalytic behaviors. The photocatalytic results show that with the increase of Co2+ content, the photodegradation properties are continuously improved from 1 to 5, which fully indicate that only changing metal ions could regulate the photodegradation properties. In detail, 1 is an inactive photocatalyst to degrade methylene blue (MB), while 5 exhibits preeminent photocatalytic properties under visible light irradiation. Moreover, 1 shows good selective sensing toward Fe3+, Cr3+, UO22+, CrO42− and Cr2O72− ions in aqueous solution. To the best of our knowledge, 1 is the first MOF example for the optical detection of Fe3+, Cr3+, UO22+, CrO42− and Cr2O72− ions in aqueous solution.
Five isomorphous Co‐Zn MOFs M (HBTC)(BMIOPE)·DMF·H2On (M = Zn (1), Zn0.7Co0.3 (2), Zn0.5Co0.5 (3), Zn0.3Co0.7 (4), Co (5), H3BTC = 1,3,5‐benzenetricarboxylic acid, BMIOPE = 4,4′‐bis(2‐methylimidazol‐1‐yl)diphenyl ether) have been synthesized, showing the photodegradation modulate by the Co2+ content. Meanwhile, 1 shows good selective sensing toward Fe3+, Cr3+, UO22+, CrO42− and Cr2O72− ions in aqueous solution.
•Amorphous and zeolite-like phases of Alkali-activated (AA)-Steel slag present after the dissolution and reorientation.•Nano-C-S-H and nano-N(C)-A-S-H gel easily densified at higher temperature ...curing condition.•Q1 and Q2(1Al) units are the main form of 29Si structure in AA-Steel slag under 60 °C curing condition.
This work aims to investigate the early age evolution of alkali-activated steel slag under curing condition of 60 °C. Microstructural characterization and reaction degree of alkali-activated steel slag (Isothermal calorimetric, scanning electron microscope, Transmission electron microscopy, Fourier Transform Infrared Spectrometer, and 29Si nuclear magnetic resonance) were carried out. The results showed that the densifying microstructure of aluminosilicate gel significantly increases, attributing to the increasing of reaction degree due to the formation of Si-O-T, in the early evolution of alkali-activated steel slag at 60 °C curing condition. The 29Si structure of Q0 in steel slag gradually converted into Q1 and Q2 in the intermediate products which represented the formation of aluminosilicate gels. The evidence indicated that the steel slag can be an alternative raw material in alkali activated application.
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