General room-temperature Suzuki-Miyaura polymerization for organic electronics.

π-Conjugated polymers (CPs) have broad applications in high-performance optoelectronics, energy storage, sensors and biomedicine. However, developing green and efficient methods to precisely synthesize alternating CP structures on a large scale remains challenging and critical for their industrialization. Here a room-temperature, scalable and homogeneous Suzuki-Miyaura-type polymerization reaction is developed with broad generality validated for 24 CPs including donor-donor, donor-acceptor and acceptor-acceptor connectivities, yielding device-quality polymers with high molecular masses. Furthermore, the polymerization protocol significantly reduces homocoupling structural defects, yielding more structurally regular and higher-performance electronic materials and optoelectronic devices than conventional thermally activated polymerizations. Experimental and theoretical studies reveal that a borate transmetalation process plays a key role in suppressing protodeboronation, which is critical for large-scale structural regularity. Thus, these results provide a general polymerization tool for the scalable production of device-quality CPs with alternating structural regularity.

Low dinosaur biodiversity in central China 2 million years prior to the end-Cretaceous mass extinction.

Whether or not nonavian dinosaur biodiversity declined prior to the end-Cretaceous mass extinction remains controversial as the result of sampling biases in the fossil record, differences in the analytical approaches used, and the rarity of high-precision geochronological dating of dinosaur fossils. Using magnetostratigraphy, cyclostratigraphy, and biostratigraphy, we establish a high-resolution geochronological framework for the fossil-rich Late Cretaceous sedimentary sequence in the Shanyang Basin of central China. We have found only three dinosaurian eggshell taxa (Macroolithus yaotunensis, Elongatoolithus elongatus, and Stromatoolithus pinglingensis) representing two clades (Oviraptoridae and Hadrosauridae) in sediments deposited between ∼68.2 and ∼66.4 million y ago, indicating sustained low dinosaur biodiversity, and that assessment is consistent with the known skeletal remains in the Shanyang and surrounding basins of central China. Along with the dinosaur eggshell records from eastern and southern China, we find a decline in dinosaur biodiversity from the Campanian to the Maastrichtian. Our results support a long-term decline in global dinosaur biodiversity prior to 66 million y ago, which likely set the stage for the end-Cretaceous nonavian dinosaur mass extinction.

Achieving Nickel-Catalyzed Reductive C(sp2)-B Coupling of Bromoboranes via Reversing the Activation Sequence.

Transition metal-catalyzed reductive cross-couplings to build C-C/Si bonds have been developed, but the reductive cross-coupling to create the C(sp2)-B bond has not been explored. Herein, we describe a nickel-catalyzed reductive cross-coupling between aryl halides and bromoboranes to construct a C(sp2)-B bond. This protocol offers a convenient approach for the synthesis of a wide range of aryl boronate esters, using readily available starting materials. Mechanistic studies indicate that the key to the success of the reaction is the activation of the B-Br bond of bromoboranes with a Lewis base such as 2-MeO-py. The activation ensures that bromoboranes will react with the active nickel(I) catalyst prior to aryl halides, which is different from the sequence of the general nickel-catalyzed reductive C(sp2)-C/Si cross-coupling, where the oxidative addition of an aryl halide proceeds first. Notably, this approach minimizes the production of undesired homocoupling byproduct without the requirement of excessive quantities of either substrate.

Radical Replacement Process for Ligated Boryl Radical-Mediated Activation of Unactivated Alkyl Chlorides for C(sp3)-C(sp3) Bond Formation.

The ligated boryl radical (LBR) has emerged as a potent tool for activating alkyl halides in radical transformations through halogen-atom transfer (XAT). However, unactivated alkyl chlorides still present an open challenge for this strategy. We herein describe a new activation mode of the LBR for the activation of unactivated alkyl chlorides to construct a C(sp3)-C(sp3) bond. Mechanistic studies reveal that the success of the protocol relies on a radical replacement process between the LBR and unactivated alkyl chloride, forming an alkyl borane intermediate as the alkyl radical precursor. Aided with the additive K3PO4, the alkyl borane then undergoes one-electron oxidation, generating an alkyl radical. The incorporation of the radical replacement activation model to activate unactivated alkyl chlorides significantly enriches LBR chemistry, which has been applied to activate alkyl iodides, alkyl bromides, and activated alkyl chlorides via XAT.

STAT5 phosphorylation plus minimal residual disease defines a novel risk classification in adult B-cell acute lymphoblastic leukaemia.

The dysregulation of the Janus family tyrosine kinase-signal transducer and activator of transcription (JAK-STAT) is closely related to acute lymphoblastic leukaemia (ALL), whereas the clinical value of phosphorylated STAT5 (pSTAT5) remains elusive. Herein we performed a prospective study on clinical significance of flow cytometry-based pSTAT5 in adult B-ALL patients. A total of 184 patients were enrolled in the Precision-Classification-Directed-Target-Total-Therapy (PDT)-ALL-2016 cohort between January 2018 and December 2021, and STAT5 phosphorylation was detected by flow cytometry at diagnosis. Based on flow-pSTAT5, the population was classified into pSTAT5low (113/184, 61.1%) and pSTAT5high (71/184, 38.9%). Overall survival (OS) and event-free survival (EFS) were inferior in pSTAT5high patients than in those with pSTAT5low (OS, 44.8% vs. 65.2%, p = 0.004; EFS, 23.5% vs. 52.1%, p < 0.001), which was further confirmed in an external validation cohort. Furthermore, pSTAT5 plus flow-based minimal residual disease (MRD) postinduction defines a novel risk classification as being high risk (HR, pSTAT5high + MRD+), standard risk (SR, pSTAT5low + MRD-) and others as moderate-risk group. Three identified patient subgroups are distinguishable with disparate survival curves (3-year OS rates, 36.5%, 56.7% and 76.3%, p < 0.001), which was confirmed on multivariate analysis (hazard ratio 3.53, p = 0.003). Collectively, our study proposed a novel, simple and flow-based risk classification by integrating pSTAT5 and MRD in favour of risk-guided treatment for B-ALL.

Adoptive therapy with cytomegalovirus-specific cytotoxic T lymphocytes for refractory cytomegalovirus DNAemia and disease after allogeneic haematopoietic stem cell transplantation.

Cytomegalovirus (CMV) DNAemia and disease are common complications in patients undergoing allogeneic haematopoietic stem cell transplantation (allo-HSCT). Few studies have compared the efficacy and safety of the HSCT donor and third-party CMV-specific cytotoxic T lymphocytes (CMV-CTLs) in the treatment of CMV DNAemia and disease. In this study, we retrospectively compared the efficacy and safety of HSCT donor and third-party CMV-CTLs in patients with refractory CMV DNAemia or disease after allo-HSCT at our centre from January 2017 to September 2021. Fifty-three patients who received CMV-CTL therapy were enrolled, including 40 in the donor group and 13 in the third-party group, and they were adults aged 18 years or older. Within 6 weeks of treatment, 26 (65.0%) and 9 (69.2%) patients achieved complete response in the donor and third-party groups (p = 1.000). The 2-year overall survival was 59.6% (95% CI 46.1%-77.1%) and 53.8% (32.6%-89.1%) in the donor and third-party groups (p = 0.860). Four (10.0%) patients in the donor group and two (15.4%) patients in the third-party group developed acute graft-versus-host disease within 3 months after CMV-CTL infusions. In conclusion, our data suggest that donor and third-party CMV-CTLs have comparable efficacy and safety for refractory CMV DNAemia and disease.

PASS-ALL study of paediatric-inspired versus adult chemotherapy regimens on survival of high-risk Philadelphia-negative B-cell acute lymphoblastic leukaemia with allogeneic haematopoietic stem cell transplantation.

This PASS-ALL study was designed to explore the effect of paediatric-inspired versus adult chemotherapy regimens on survival of adolescents and young adults (AYA) with high-risk Philadelphia chromosome-negative B-cell acute lymphoblastic leukaemia (HR PH-ve B-cell ALL) eligible for allogeneic haematopoietic stem cell transplantation (allo-HSCT). The PASS-ALL study is a multicentre, observational cohort study, and 143 patients with HR B-cell PH-ve ALL were enrolled from five centres-77 patients allocated in the paediatric-inspired cohort and 66 in the adult cohort with comparable baseline characteristics. Of the 143 patients, 128 cases underwent allo-HSCT. Three-year leukaemia-free survival (LFS) in the paediatric-inspired cohort was 72.2% (95% CI 60.8%-83.6%) compared with 44.6% (95% CI 31.9%-57.3%; p = 0.001). Furthermore, time-to-positive minimal residual disease (TTP-MRD) post-HSCT was marked different, 3-year cumulative incidence of relapse was 25.9% (95% CI 15.8%-37.2%) in paediatric cohort and 45.4% (95% CI 40.0%-57.9%) in adult cohort (p = 0.026). Finally, the 3-year OS rate was 75.3% (95% CI 64.9%-85.7%) for the paediatric-inspired cohort and 64.1% (95% CI 51.8%-76.4%) for the adult cohort (p = 0.074). On a multivariate analysis, paediatric-inspired regimen is a predictive factor for LFS (HR = 2.540, 95% CI 1.327-4.862, p = 0.005). Collectively, our data suggest that paediatric-inspired chemotherapy pre-HSCT results in deeper and durable MRD response reduces relapse post-HSCT and improves survival in HR B-cell PH-ve ALL patients with allo-HSCT.

Superior survival with allogeneic hematopoietic stem cell transplantation versus chemotherapy for high-risk adult acute lymphoblastic leukemia in a PDT-ALL-2016 pediatric-inspired cohort.

Not available.

An Efficient C-Si/C-H Cross-Coupling Reaction Enabled by a Radical Pathway.

The methods for the cross-coupling of aryl(trialkyl)silanes are long-standing challenges due to the extreme inertness of C-Si(R3) bond, though the reaction is environmentally friendly and highly regioselective to synthesize biaryls. Herein, we report a copper-catalyzed cross-coupling of aryl(trialkyl)silanes and aryl via a radical mechanism. The reaction proceeds efficiently with aryl sulfonium salts as limiting reagents, exhibits broad substrate scope, and provides an important synthetic strategy to acquire biaryls, exemplified by unsymmetrical fluorescence probes and late-stage functionalization of drugs. Of note, the experimental and theoretical mechanistic studies revealed a radical mechanism where the copper catalyst and CsF play critical roles on the radical generation and desilylation process.

Mutations of epigenetic modifier genes predict poor outcome in adult acute lymphoblastic leukemia.

Epigenetic modifier (EM) genes play important roles in the occurrence and progression of acute lymphoblastic leukemia (ALL). However, the prognostic significance of EM mutations in ALL has not yet been thoroughly investigated. This retrospective study included 205 adult patients with ALL engaged in a pediatric-type regimen. Based on targeted next-generation sequencing, they were divided into EM mutation group (EM-mut, n = 75) and EM wild-type group (EM-wt, n = 130). The EM-mut group showed a higher positive rate of minimal residual disease (MRD) on treatment day24 and before consolidation therapy (P = 0.026, 0.020). Multivariate Cox regression analysis showed that EM-mut was an independent adverse factor for overall survival (OS) and event-free survival (EFS) (HR = 2.123, 1.742; P = 0.009, 0.007). Survival analysis revealed that the OS and EFS rates were significantly lower in the EM-mut group than in the EM-wt group (3-year OS rate, 45.8% vs. 65.0%, P = 0.0041; 3-year EFS rate, 36.7% vs. 53.2%, P = 0.011). In conclusion, EM was frequently mutated in adult ALL and was characterized by poor response to induction therapy and inferior clinical outcomes.

UV-Transparent SHG Material Explored in an Alkali Metal Sulfate Selenite System.

The first examples of alkali metal selenite sulfates, namely, Na8(SeO3)(SO4)3 (1), Na2(H2SeO3)(SO4) (2), and K4(H2SeO3)(HSO4)2(SO4) (3), were successfully synthesized by hydrothermal reactions. Their structures display three different zero-dimensional configurations composed of isolated sulfate tetrahedra and selenite groups separated by alkali metals. Na8(SeO3)(SO4)3 (1) features a noncentrosymmetric structure, while Na2(H2SeO3)(SO4) (2) and K4(H2SeO3)(HSO4)2(SO4) (3) are centrosymmetric. Powder second-harmonic-generation measurements revealed that Na8(SeO3)(SO4)3 (1) shows a phase-matchable SHG intensity about 1.2 times that of KDP. UV-vis-NIR diffuse reflectance spectroscopic analysis indicated that Na8(SeO3)(SO4)3 (1) has a short UV cutoff edge and a large optical band gap, which makes it a possible UV nonlinear optical material. Theoretical calculations revealed that the birefringence of Na8(SeO3)(SO4)3 (1) is 0.041 at 532 nm, which is suitable for phase-matching condition. This work provides a good experimental foundation for the exploration of new UV nonlinear crystals in an alkali metal selenite sulfate system.

Associations Between Metabolic Obesity Phenotypes and Pathological Characteristics of Papillary Thyroid Carcinoma.

OBJECTIVE: The association between obesity, metabolic dysregulation, and the aggressive pathological traits of papillary thyroid carcinoma (PTC) continues to be a contentious issue. To date, no investigations have examined the impact of metabolic status on the malignant pathological features of PTC in relation to obesity. METHODS: This research involved 855 adult patients with PTC from Shandong Provincial Hospital, classified into 4 groups based on metabolic and obesity status: metabolically healthy nonobese, metabolically unhealthy nonobese (MUNO), metabolically healthy obese, and metabolically unhealthy obese. We employed logistic regression to investigate the relationship between these metabolic obesity phenotypes and PTC's pathological characteristics. Mediation analysis was also performed to determine metabolic abnormalities' mediating role in the nexus between obesity and these characteristics. RESULTS: Relative to metabolically healthy nonobese individuals, the metabolically unhealthy obese group was significantly associated with an elevated risk of larger tumor sizes and a greater number of tumor foci in PTC. Mediation analysis indicated that obesity directly influences tumor size, whereas its effect on tumor multifocality is mediated through metabolic dysfunctions. Specifically, high-density lipoprotein cholesterol levels were notably associated with tumor multifocality within obese subjects, serving as a mediator in obesity's impact on this trait. CONCLUSION: The concurrent presence of obesity and metabolic dysregulation is often connected to more aggressive pathological features in PTC. The mediation analysis suggests obesity directly affects tumor size and indirectly influences tumor multifocality via low high-density lipoprotein cholesterol levels.

A multi-Task Learning based applicable AI model simultaneously predicts stage, histology, grade and LNM for cervical cancer before surgery.

PURPOSE: To build an Mult-Task Learning (MTL) based Artificial Intelligence(AI) model that can simultaneously predict clinical stage, histology, grade and LNM for cervical cancer before surgery. METHODS: This retrospective and prospective cohort study was conducted from January 2001 to March 2014 for the training set and from January 2018 to November 2021 for the validation set at Beijing Chaoyang Hospital, Capital Medical University. Preoperative clinical information of cervical cancer patients was used. An Artificial Neural Network (ANN) algorithm was used to build the MTL-based AI model. Accuracy and weighted F1 scores were calculated as evaluation indicators. The performance of the MTL model was compared with Single-Task Learning (STL) models. Additionally, a Turing test was performed by 20 gynecologists and compared with this AI model. RESULTS: A total of 223 cervical cancer cases were retrospectively enrolled into the training set, and 58 cases were prospectively collected as independent validation set. The accuracy of this cervical cancer AI model constructed with ANN algorithm in predicting stage, histology, grade and LNM were 75%, 95%, 86% and 76%, respectively. And the corresponding weighted F1 score were 70%, 94%, 86%, and 76%, respectively. The average time consumption of AI simultaneously predicting stage, histology, grade and LNM for cervical cancer was 0.01s (95%CI: 0.01-0.01) per 20 patients. The mean time consumption doctor and doctor with AI were 581.1s (95%CI: 300.0-900.0) per 20 patients and 534.8s (95%CI: 255.0-720.0) per 20 patients, respectively. Except for LNM, both the accuracy and F-score of the AI model were significantly better than STL AI, doctors and AI-assisted doctors in predicting stage, grade and histology. (P < 0.05) The time consumption of AI was significantly less than that of doctors' prediction and AI-assisted doctors' results. (P < 0.05 CONCLUSION: A multi-task learning AI model can simultaneously predict stage, histology, grade, and LNM for cervical cancer preoperatively with minimal time consumption. To improve the conditions and use of the beneficiaries, the model should be integrated into routine clinical workflows, offering a decision-support tool for gynecologists. Future studies should focus on refining the model for broader clinical applications, increasing the diversity of the training datasets, and enhancing its adaptability to various clinical settings. Additionally, continuous feedback from clinical practice should be incorporated to ensure the model's accuracy and reliability, ultimately improving personalized patient care and treatment outcomes.

Predicting axillary lymph node metastasis in breast cancer based on ultrasound radiofrequency time-series analysis.

BACKGROUND: The status of axillary lymph nodes (ALN) plays a critical role in the management of patients with breast cancer. It is an urgent demand to develop highly accurate, non-invasive methods for predicting ALN status. PURPOSE: To evaluate the efficacy of ultrasound radiofrequency (URF) time-series parameters, in combination with clinical data, in predicting ALN metastasis in patients with breast cancer. MATERIAL AND METHODS: We prospectively gathered clinicopathologic and ultrasonic data from patients diagnosed with breast cancer. Various machine-learning (ML) models were developed using all available features to determine the most efficient diagnostic model. Subsequently, distinct prediction models were created using the optimal ML model, and their diagnostic performances were evaluated and compared. RESULTS: The study encompassed 240 patients, of whom 88 had lymph node metastases. A leave-one-out cross-validation (LOOCV) method was used to split the entire dataset into training and testing subsets. The random forest ML model outperformed the other algorithms, with an area under the curve (AUC) of 0.92. Prediction models based on clinical, ultrasonic, URF parameters, clinical + ultrasonic, clinical + URF, and ultrasonic + URF parameters had AUCs of 0.56, 0.79, 0.78, 0.90, 0.80, and 0.84, respectively, in the testing set. The comprehensive diagnostic model (clinical + ultrasonic + URF parameters) demonstrated strong diagnostic capability, with an AUC of 0.94 in the testing set, exceeding any single prediction model. CONCLUSION: The combined model (clinical + ultrasonic + URF parameters) could be used preoperatively to predict lymph node status, offering valuable input for the design of individualized surgical approaches.

Ultrasound Spectral Combined With Clinical Pathological Parameters in Prediction of Axillary Lymph Node Metastatic in Breast Cancer.

OBJECTIVES: To explore the clinical value of the nomogram based on ultrasound spectral combined with clinical pathological parameter in predicting axillary lymph node metastasis in breast cancer. METHODS: We prospectively gathered clinicopathologic and ultrasonic data from 240 patients confirmed breast cancer. The risk factors of axillary lymph node metastasis were analyzed by univariate and multivariate logistic regression, and the prediction model was established. The model calibration, predictive ability, and diagnostic efficiency in the training set and the testing set were analyzed by receiver operating characteristic curve and calibration curve analysis, respectively. RESULTS: Univariate analysis showed that lymph node metastasis was related with tumor size, Ki-67, axillary ultrasound, ultrasound spectral quantitative parameter, internal echo, and calcification (P < .05). Multivariate logistic regression analysis showed that the Ki-67, axillary ultrasound, quantitative parameter (the mean of the mid-band fit in tumor and posterior tumor) were independent risk factors of axillary lymph node metastasis (P < .05). The models developed using Ki-67, axillary ultrasound, and quantitative parameters for predicting axillary lymph node metastasis demonstrated an area under the receiver operating characteristic curve of 0.83. Additionally, the prediction model exhibited outstanding predictability for axillary lymph node metastasis, as evidenced by a Harrell C-index of 0.83 (95% confidence interval 0.73-0.93). CONCLUSION: Axillary ultrasound combined with Ki-67 and ultrasound spectral parameters has the potential to predict axillary lymph node metastasis in breast cancer, which is superior to axillary ultrasound alone.

Curcumin alleviates zearalenone-induced liver injury in mice by scavenging reactive oxygen species and inhibiting mitochondrial apoptosis pathway.

Curcumin (CUR) is a compound extracted from turmeric that has a variety of functions including antioxidant and anti-inflammatory. As an estrogen-like mycotoxin, zearalenone (ZEN) not only attacks the reproductive system, but also has toxic effects on the liver. However, whether CUR can alleviate ZEN-induced liver injury remains unclear. This paper aims to investigate the protective effect of CUR against ZEN-induced liver injury in mice and explore the molecular mechanism involved. BALB/c mice were randomly divided into control (CON) group, CUR group (200 mg/kg b. w. CUR), ZEN group (40 mg/kg b. w. ZEN) and CUR+ZEN group (200 mg/kg b. w. CUR+40 mg/kg b. w. ZEN). 28 d after ZEN exposure and CUR treatment, blood and liver samples were collected for subsequent testing. The results showed that CUR reversed ZEN-induced hepatocyte swelling and necrosis in mice. It significantly reduced the serum alkaline phosphatase (ALP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in mice (p < 0.05). In addition, CUR significantly reduced hepatic ROS, malondialdehyde, hydrogen peroxide and apoptosis levels in mice (p < 0.05). Quantitative RT-PCR and Western blot results showed that CUR significantly reduced the expression of Bax and Caspase3, and reversed the increase of Nrf2, HO-1 and NQO1 expression in the liver of mice induced by ZEN (p < 0.05). In conclusion, CUR alleviated ZEN-induced liver injury in mice by scavenging ROS and inhibiting the mitochondrial apoptotic pathway.

Artificial neural network prediction of postoperative complications in papillary thyroid microcarcinoma based on preoperative ultrasonographic features.

OBJECTIVE: To predict post-thyroidectomy complications in papillary thyroid microcarcinoma (PTMC) patients using a deep learning model based on preoperative ultrasonographic features. This study addresses the global rise in PTMC incidence and the challenges in treatment decision-making with high-resolution ultrasonography. METHOD: This study enrolled 1638 patients with clinically staged cN0 PTMC who received surgical treatment from 1997 to 2019 at Beijing Friendship Hospital. Deep learning model was developed using fully connected neural network. Feature selection included 1000 iterations of Bootstrap sampling and Recursive Feature Elimination (RFE) to identify the top 10 features. Data preprocessing involved normalization and imputation for missing values. SMOTE addressed class imbalance. The model was trained and tested on random data split, with performance metrics including Accuracy (ACC), Area Under the Curve (AUC), Sensitivity (SEN), and Specificity (SPE), visualized through a ROC curve and confusion matrix. RESULTS: The fully connected deep neural network model demonstrated high accuracy (ACC 0.81), Area Under the Curve (AUC 0.74), sensitivity (SEN 0.65), and specificity (SPE 0.83) and visualized by ROC curve and confusion matrix. These results highlight the model's reliability and potential as an effective tool in predicting postoperative complications and assisting in clinical decision-making for PTMC patients. CONCLUSION: This study highlights the potential of deep learning in enhancing medical predictions and personalized healthcare. Despite promising results, limitations include a single-center data source and unconsidered factors like lifestyle and genetics. Future research should expand data sources, include more influencing factors, and refine algorithms to improve accuracy and applicability in thyroid cancer treatment.

Critical steps in the restoration of coal mine soils: Microbial-accelerated soil reconstruction.

Soil reconstruction is a critical step in the restoration of environments affected by mining activities. This paper provides a comprehensive review of the significant role that microbial processes play in expediting soil structure formation, particularly within the context of mining environment restoration. Coal gangue and flotation tailings, despite their low carbon content and large production volumes, present potential substrates for soil reclamation. These coal-based solid waste materials can be utilized as substrates to produce high-quality soil and serve as an essential carbon source to enhance poor soil conditions. However, extracting active organic carbon components from coal-based solid waste presents a significant challenge due to its complex mineral composition. This article offers a thorough review of the soilization process of coal-based solid waste under the influence of microorganisms. It begins by briefly introducing the primary role of in situ microbial remediation technology in the soilization process. It then elaborates on various improvements to soil structure under the influence of microorganisms, including the enhancement of soil aggregate structure and soil nutrients. The article concludes with future recommendations aimed at improving the efficiency of soil reconstruction and restoration, reducing environmental risks, and promoting its application in complex environments. This will provide both theoretical and practical support for more effective environmental restoration strategies.

Enantioselective Synthesis of Axially Chiral Diaryl Ethers via NHC Catalyzed Desymmetrization and Following Resolution.

Axially chiral diaryl ethers are present in numerous natural products and bioactive molecules. However, only few catalytic enantioselective approaches have been established to access diaryl ether atropisomers. Herein, we report the N-heterocyclic carbene-catalyzed enantioselective synthesis of axially chiral diaryl ethers via desymmetrization of prochiral 2-aryloxyisophthalaldehydes with aliphatic alcohols, phenol derivatives, and heteroaromatic amines. This reaction features mild reaction conditions, good functional group tolerance, broad substrate scope and excellent enantioselectivity. The utility of this methodology is illustrated by late-stage functionalization, gram-scale synthesis, and diverse enantioretentive transformations. Control experiments and DFT calculations support the association of NHC-catalyzed desymmetrization with following kinetic resolution to enhance the enantioselectivity.

Idarubicin plus BuCy versus BuCy conditioning regimens for intermediate-risk acute myeloid leukemia in first complete remission undergoing auto-HSCT: An open-label, multicenter, randomized phase 3 trial.

We report a randomized prospective phase 3 study, designed to evaluate the efficacy and tolerability of idarubicin plus busulfan and cyclophosphamide (IDA-BuCy) versus BuCy in autologous hematopoietic stem-cell transplantation (auto-HSCT) for intermediate-risk acute myeloid leukemia (IR-AML) patients in first complete remission (CR1). One hundred and fifty-four patients were enrolled and randomized to receive IDA-BuCy (IDA 15 mg/m2/day on days -12 to -10, Bu 3.2 mg/kg/day on days -7 to -4, and Cy 60 mg/kg/day on days -3 to -2) or BuCy. The 2-year incidence of relapse was 15.6% and 19.5% in IDA-BuCy and BuCy groups (p = 0.482), respectively. There was no significant overall survival (OS) and disease-free survival (DFS) benefit for IR-AML patients receiving IDA-BuCy (2-year OS 81.8% in IDA-BuCy vs. 83.1% in BuCy, p = 0.798; 2-year DFS 76.6% in IDA-BuCy vs. 79.2% in BuCy, p = 0.693). Grade 3 or worse regimen-related toxicity (RRT) was reported for 22 (28.9%) of 76 and 9 (12.0%) of 75 patients in two groups (p = 0.015), respectively. AEs within 100 days with an outcome of death were reported for 4 (5.3%) and 0 patients in two groups. In conclusion, IDA-BuCy has higher RRT and similar anti-leukemic activity compared with BuCy in IR-AML patients in CR1 undergoing auto-HSCT. Thus, caution should be taken when choosing IDA-BuCy for IR-AML patients in CR1 with auto-HSCT. This trial is registered with ClinicalTrials.gov, NCT02671708, and is complete.