Heterogeneous-Structured Molybdenum Diboride as a Novel and Promising Anode for Lithium-Ion Batteries.

With the development of electric vehicles, exploiting anode materials with high capacity and fast charging capability is an urgent requirement for lithium-ion batteries (LIBs). Borophene, with the merits of high capacity, high electronic conductivity and fast diffusion kinetics, holds great potential as anode for LIBs. However, it is difficult to fabricate for the intrinsic electron-deficiency of boron atom. Herein, heterogeneous-structured MoB2 (h-MoB2 ) with amorphous shell and crystalline core, is prepared by solid phase molten salt method. As demonstrated, crystalline core can encapsulate the honeycomb borophene within two adjacent Mo atoms, and amorphous shell can accommodate more lithium ions to strengthen the lithium storage capacity and diffusion kinetics. According to theoretical calculations, the lithium adsorption energy in MoB2 is about -2.7 eV, and the lithium diffusion energy barrier in MoB2 is calculated to be 0.199 eV, guaranteeing the enhanced adsorption capability and fast diffusion kinetic behavior of Li+ ions. As a result, h-MoB2 anode presents high capacity of 798 mAh g-1 at 0.1 A g-1 , excellent rate performance of 183 mAh g-1 at 5 A g-1 and long-term cyclic stability for 1200 cycles. This work may inspire ideas for the fabrication of borophene analogs and two-dimensional metal borides.

CDSKNNXMBD: a novel clustering framework for large-scale single-cell data based on a stable graph structure.

BACKGROUND: Accurate and efficient cell grouping is essential for analyzing single-cell transcriptome sequencing (scRNA-seq) data. However, the existing clustering techniques often struggle to provide timely and accurate cell type groupings when dealing with datasets with large-scale or imbalanced cell types. Therefore, there is a need for improved methods that can handle the increasing size of scRNA-seq datasets while maintaining high accuracy and efficiency. METHODS: We propose CDSKNNXMBD (Community Detection based on a Stable K-Nearest Neighbor Graph Structure), a novel single-cell clustering framework integrating partition clustering algorithm and community detection algorithm, which achieves accurate and fast cell type grouping by finding a stable graph structure. RESULTS: We evaluated the effectiveness of our approach by analyzing 15 tissues from the human fetal atlas. Compared to existing methods, CDSKNN effectively counteracts the high imbalance in single-cell data, enabling effective clustering. Furthermore, we conducted comparisons across multiple single-cell datasets from different studies and sequencing techniques. CDSKNN is of high applicability and robustness, and capable of balancing the complexities of across diverse types of data. Most importantly, CDSKNN exhibits higher operational efficiency on datasets at the million-cell scale, requiring an average of only 6.33 min for clustering 1.46 million single cells, saving 33.3% to 99% of running time compared to those of existing methods. CONCLUSIONS: The CDSKNN is a flexible, resilient, and promising clustering tool that is particularly suitable for clustering imbalanced data and demonstrates high efficiency on large-scale scRNA-seq datasets.

Haploidentical haematopoietic stem cell transplantation combined with post-transplant cyclophosphamide in neuronal ceroid lipofuscinosis: Experience in eight patients / Trasplante de progenitores hematopoyéticos haploidénticos con ciclofosfamida postrasplante en lipofuscinosis neuronal ceroidea: experiencia en 8 pacientes

Background: Neuronal ceroid lipofuscinoses (NCLs) are rare lysosomal storage disorders characterized by progressive mental retardation and motor developmental regression and myoclonic seizures. Hematopoietic stem cell transplantation (HSCT) has been suggested to be used in the treatment of lysosomal disorders and brain damage caused by a deficiency of soluble lysosomal enzymes. There are no previous reports on treating NCLs with HSCT in China. Material and method: NCL pediatric patients who underwent allo-HSCT at Affiliated Children's Hospital of Capital Institute of Pediatrics were involved. A combination of medical histories, clinical features, and genetic analyses was used for the diagnosis of all patients. The written consent form for allo-HSCT was attained from the patient's guardian, which was then reviewed and approved by the ethics committee before the procedure. Results: From January 2018 to May 2019, the haplo-HSCT followed by PT/Cy on eight NCL pediatric patients was performed. The median age was 4.5 years (ranging from 2.8 to 7 years). The donors were their haploidentical HLA-matched parents, as no identically matched donors were found. The median nucleated cell count was 25.37 (10–34.41)×108/kg, and the median CD34+ count was 13.7 (8.95–22)×106/kg. Neutrophil reconstitution occurred 12 days (11–14 days) after transplantation, and the median platelet reconstitution time was 12 days (9–14 days) after transplantation. All patients achieved full donor chimerism and did not develop Grade II–IV acute GvHD or chronic GvHD after transplantation. The median follow-up period was 2.2 (1.5–2.6) years. All patients are still alive at present and develop no severe transplantation-related complications. The mental motor disorders, myoclonic seizures, and vision loss of all patients continued to progress. However, the progression slowed at 12 months after transplantation.(AU)

Antecedentes: Las lipofuscinosis neuronales ceroides (NCL) son trastornos raros del almacenamiento lisosomal caracterizados por retraso mental progresivo y regresión del desarrollo motor y convulsiones mioclónicas. Se ha sugerido que el trasplante de células madre hematopoyéticas (HSCT) se utilice en el tratamiento de trastornos lisosomales y daño cerebral causado por una deficiencia de enzimas lisosomales solubles. No hay informes previos sobre el tratamiento de NCL con HSCT en China. Material y método: Pacientes pediátricos de NCL que se sometieron a alo-TCMH en el Hospital de Niños Afiliado del Instituto Capital de Pediatría involucrados. Se utilizó una combinación de historias clínicas, características clínicas y análisis genéticos para el diagnóstico de todos los pacientes. El formulario de consentimiento por escrito para el allo-TCMH se obtuvo del tutor del paciente, que luego fue revisado y aprobado por el comité de ética antes del procedimiento.Resultados: De enero de 2018 a mayo de 2019, se realizó el haplo-HSCT seguido de TP/Cy en 8 pacientes pediátricos con NCL. La mediana de edad fue de 4,5 años (variando de 2,8 a 7 años). Los donantes eran sus padres haploidénticos compatibles con HLA, ya que no se encontraron donantes idénticos. La mediana del recuento de células nucleadas fue de 25,37 (10–34,41)×108/kg, y la mediana del recuento de CD34+ fue de 13,7 (8,95-22)×106/kg. La reconstitución de neutrófilos ocurrió 12 días (11-14 días) después del trasplante, y el tiempo medio de reconstitución plaquetaria fue de 12 días (9-14 días) después del trasplante. Todos los pacientes alcanzaron quimerismo total del donante y no desarrollaron EICH aguda de grado II-IV o EICH crónica después del trasplante. La mediana del período de seguimiento fue de 2,2 (1,5–2,6) años. Todos los pacientes siguen vivos en la actualidad y no desarrollan complicaciones graves relacionadas con el trasplante...(AU)

Efficient Raman Lasing and Raman-Kerr Interaction in an Integrated Silicon Carbide Platform.

Implementing stimulated Raman scattering in a low-loss microresonator could lead to Raman lasing. Here, we report the demonstration of an efficient Raman laser with >50% power efficiency in an integrated silicon carbide platform for the first time. By fine-tuning the free spectral range (FSR) of 43 µm-radius silicon carbide microresonators, the Stokes resonance corresponding to the dominant Raman shift of 777 cm-1 (23.3 THz) is aligned to the center of the Raman gain spectrum, resulting in a low power threshold of 2.5 mW. The peak Raman gain coefficient is estimated to be (0.75 ± 0.15) cm/GW in the 1550 nm band, with an approximate full width at half-maximum of (120 ± 30) GHz. In addition, the microresonator is designed to exhibit normal dispersion at the pump wavelength near 1550 nm while possessing anomalous dispersion at the first Stokes near 1760 nm. At high enough input powers, a Kerr microcomb is generated by the Stokes signal acting as the secondary pump, which then mixes with the pump laser through four-wave mixing to attain a wider spectral coverage. Furthermore, cascaded Raman lasing and the occurrence of multiple Raman shifts, including 204 cm-1 (6.1 THz) and 266 cm-1 (8.0 THz) transitions, are also observed. Finally, we show that the Stokes Raman could also help broaden the spectrum in a Kerr microcomb which has anomalous dispersion at the pump wavelength. Our example of a 100 GHz-FSR microcomb has a wavelength span from 1200 to 1900 nm with 300 mW on-chip power.

Construction of magnetic azo-linked porous polymer for highly-efficient enrichment and separation of phenolic endocrine disruptors from environmental water and fish.

Developing effective methods for highly sensitive detection of phenolic endocrine disruptors (EDCs) is especially urgent. Herein, a magnetic hydroxyl-functional porous organic polymer (M-FH-POP) was facilely synthesized by green diazo-couple reaction using basic fuchsin and hesperetin as monomer for the first time. M-FH-POP delivered superior adsorption performance for phenolic EDCs. The adsorption mechanism was hydrogen bonds, hydrophobic interaction and π-π interplay. With M-FH-POP as adsorbent, a magnetic solid phase extraction method was established for extracting trace phenolic EDCs (bisphenol A, 4-tert-butylphenol, bisphenol F and bisphenol B) in water and fish before ultra-high performance liquid chromatography tandem mass spectrometry analysis. The method displayed low detection limit (S/N = 3) of 0.05-0.15 ng mL-1 for water and 0.08-0.3 ng g-1 for fish. The spiked recoveries were 88.3 %-109.8 % with the relative standard deviations of 2.4 %-6.4 %. The method offers a new strategy for sensitive determination of phenolic EDCs in water and fish samples.

Interlayer Engineering of Layered Materials for Efficient Ion Separation and Storage.

Layered materials are characterized by strong in-plane covalent chemical bonds within each atomic layer and weak out-of-plane van der Waals (vdW) interactions between adjacent layers. The non-bonding nature between neighboring layers naturally results in a vdW gap, which enables the insertion of guest species into the interlayer gap. Rational design and regulation of interlayer nanochannels are crucial for converting these layered materials and their 2D derivatives into ion separation membranes or battery electrodes. Herein, based on the latest progress in layered materials and their derivative nanosheets, various interlayer engineering methods are briefly introduced, along with the effects of intercalated species on the crystal structure and interlayer coupling of the host layered materials. Their applications in the ion separation and energy storage fields are then summarized, with a focus on interlayer engineering to improve selective ion transport and ion storage performance. Finally, future research opportunities and challenges in this emerging field are comprehensively discussed.

Haploidentical haematopoietic stem cell transplantation combined with post-transplant cyclophosphamide in neuronal ceroid lipofuscinosis: Experience in eight patients.

BACKGROUND: Neuronal ceroid lipofuscinoses (NCLs) are rare lysosomal storage disorders characterized by progressive mental retardation and motor developmental regression and myoclonic seizures. Hematopoietic stem cell transplantation (HSCT) has been suggested to be used in the treatment of lysosomal disorders and brain damage caused by a deficiency of soluble lysosomal enzymes. There are no previous reports on treating NCLs with HSCT in China. MATERIAL AND METHOD: NCL pediatric patients who underwent allo-HSCT at Affiliated Children's Hospital of Capital Institute of Pediatrics were involved. A combination of medical histories, clinical features, and genetic analyses was used for the diagnosis of all patients. The written consent form for allo-HSCT was attained from the patient's guardian, which was then reviewed and approved by the ethics committee before the procedure. RESULTS: From January 2018 to May 2019, the haplo-HSCT followed by PT/Cy on eight NCL pediatric patients was performed. The median age was 4.5 years (ranging from 2.8 to 7 years). The donors were their haploidentical HLA-matched parents, as no identically matched donors were found. The median nucleated cell count was 25.37 (10-34.41)×108/kg, and the median CD34+ count was 13.7 (8.95-22)×106/kg. Neutrophil reconstitution occurred 12 days (11-14 days) after transplantation, and the median platelet reconstitution time was 12 days (9-14 days) after transplantation. All patients achieved full donor chimerism and did not develop Grade II-IV acute GvHD or chronic GvHD after transplantation. The median follow-up period was 2.2 (1.5-2.6) years. All patients are still alive at present and develop no severe transplantation-related complications. The mental motor disorders, myoclonic seizures, and vision loss of all patients continued to progress. However, the progression slowed at 12 months after transplantation. CONCLUSION: This study demonstrated that it is safe and efficacious to treat NCLs with haplo-HSCT. Transplantation should be performed at an early stage for the survival quality of pediatric patients.

Green construction of magnetic azo porous organic polymer for highly efficient enrichment and detection of phenolic endocrine disruptors.

Porous organic polymers (POPs) are prominent sorbents for effective extraction of endocrine disrupting chemicals (EDCs). However, green and sustainable construction of functional POPs is still challenging. Herein, we developed a magnetic azo POP (Mazo-POP) for the first time using hydroxy-rich natural kaempferol and low-toxic basic fuchsin as monomers through a diazo coupling reaction. The Mazo-POP exhibited excellent extraction capabilities for EDCs with a phenolic structure. Consequently, it was used as a magnetic sorbent for extracting phenolic EDCs from water and fish samples, followed by ultrahigh-performance liquid chromatography-tandem mass spectrometric detection. The Mazo-POP based analytical method afforded a good linearity of 0.06-100 ng mL-1 and 0.3-500 ng g-1 for water and fish samples respectively, with detection limits (S/N = 3) of 0.02-0.5 ng mL-1 and 0.1-1.5 ng g-1, respectively. The method recovery was from 85.2% to 109% and relative standard deviation was less 5.3%. Moreover, the effective adsorption was mainly contributed by hydrogen bond, π-π interaction, pore filling and hydrophobic interaction. This work not only provides an efficient method for sensitive determination of phenolic EDCs, but also highlights the significance of green preparation of environmentally friendly sorbents for enriching/adsorbing pollutants.

Improving few-shot relation extraction through semantics-guided learning.

Few-shot relation extraction (few-shot RE) aims to recognize relations between the entity pair in a given text by utilizing very few annotated instances. As a simple yet efficient approach, prototype network-based methods often directly incorporate relation information to enhance prototype representation or leverage contrastive learning to mitigate prediction confusion. Despite achieving good results, the above methods are still susceptible to false judgments of outlier samples and confusion of similar classes. To address these issues, we propose a novel Semantics-Guided Learning (SemGL) method that more effectively utilizes relation information to enhance both the representations of instances and prototypes for improving the performance of few-shot RE. First, SemGL employs the prompt encoder to encode various prompt templates of instances and relation information and obtains more accurate semantic representations of instances, instance prototypes, and concept prototypes via the prompt enhancement from large language models. Then, SemGL introduces a novel technique called relation graph learning, which leverages concept prototypes to cluster homogeneous instances together, emphasizing relation-specific features of concrete instances. Simultaneously, SemGL employs instance-level contrastive learning between instance prototypes and support instances to distinguish between intra-class instances and inter-class instances to promote shared features among intra-class instances. Additionally, prototype-level contrastive learning leverages concept prototypes to pull closer relation-specific features of the concept prototype and shared features of the instance prototype from the same relation. Finally, SemGL utilizes new relation prototypes that integrate interpretable features of concept prototypes and shared features of instance prototypes for prediction. Experimental results on two publicly available few-shot RE datasets demonstrate the effectiveness and efficiency of SemGL in introducing relation information, with particularly promising results for the domain adaptation challenge task.

Regression equation for predicting dietary phosphorus intake based on estimated dietary protein intake: A multicenter cross-sectional study in China.

BACKGROUND: Protein and phosphorus intake, which affect chronic kidney disease (CKD), is assessed using cumbersome food diaries. Therefore, more straightforward and accurate methods of assessing protein and phosphorus intake are needed. We decided to investigate the nutrition status and dietary protein and phosphorus intake of patients with stages 3, 4, 5, or 5D CKD. METHODS: This cross-sectional survey included outpatients with CKD at seven class A tertiary hospitals in Beijing, Shanghai, Sichuan, Shandong, Liaoning, and Guangdong in China. Protein and phosphorus intake levels were calculated using 3-day food records. Protein levels and calcium and phosphorus serum concentrations were measured; urinary urea nitrogen was determined using a 24-h urine test. Protein and phosphorus intakes were calculated using the Maroni and Boaz formulas, respectively. The calculated values were compared with the recorded dietary intakes. An equation that regressed phosphorus intake on protein intake was constructed. RESULTS: The average recorded energy and protein intake was 1637.5 ± 595.74 kcal/day and 56.97 ± 25.25 g/day, respectively. Overall, 68.8% of patients had a good nutrition status (grade A on the Subjective Global Assessment). The correlation coefficient between protein intake and calculated intake was 0.145 (P = 0.376) and that between phosphorus intake and calculated intake was 0.713 (P < 0.001). CONCLUSION: Protein and phosphorus intakes correlated linearly. Chinese patients with stage 3-5 CKD had low daily energy intake but high protein intake. Malnutrition was present in 31.2% of patients with CKD. The phosphorus intake could be estimated from the protein intake.

The role and mechanism of AZD5363 anti-leukemia activity in T-cell acute lymphoblastic leukemia.

BACKGROUND: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive and heterogeneous hematologic malignancy. Chemotherapy resistance and refractory relapses are the most important challenges in T-ALL. PI3K/Akt/mTOR pathway has been implicated in regulating cell survival, T-ALL development and resistance to chemotherapy. We explored the effects of AZD5363 (a potent pan-Akt inhibitor) alone and in combination with autophagy inhibitor hydroxycholoroquine sulfate (HCQ) in cultured CCRF-CEM, Jurkat and PF382 cells and a T-ALL xenograft mouse model. METHODS: A xenograft mouse model was used to investigate the effect of AZD5363 on T-ALL progression. MTT assay, flow cytometry, siRNA, transmission electron microscopy and western blotting were performed in cultured CCRF-CEM, Jurkat and PF382 cells. The interaction between AZD5363 and HCQ was explored by molecular docking. RESULTS: AZD5363 delayed T-ALL progression and increased the expression of cleaved caspase-3 and LC3B-II in mice. AZD5363 decreased cells viability by arresting cell cycle in the G1 phase and inducing apoptosis, and, significantly increased the number of autophagosomes (p < 0.01). The increased expression of cleaved caspase-3 and LC3B-II, and phosphorylation of Akt and mTOR were significantly, inhibited by AZD5363. HCQ blocked AZD5363-induced autophagy and enhanced AZD5363-induced cell death (p < 0.01). CONCLUSIONS: AZD5363 suppressed T-ALL progression and its anti-leukemia activity was enhanced by HCQ in T-ALL cells, which might provide a potential therapeutic strategy for human T-ALL.

Fluorine-functionalized covalent organic framework as efficient solid phase extraction sorbent for adsorption of aflatoxins in nuts.

In this study, a new fluorine-functionalized covalent organic framework (F-COF) was designed and fabricated by the direct polycondensation of tris(4-aminophenyl)amine and 2,3,5,6-tetra-fluoroterephthaldehyde for the first time. F-COF exhibited a remarkably enhanced adsorption capability compared with that of the fluorine-free COF. The favorable adsorption of aflatoxins was attributed to multiple interactions including pseudo hydrogen bond, F-O, π-π, F-π interactions and hydrophobic interactions between F-COF and aflatoxins. By coupling F-COF based solid phase extraction with high-performance liquid chromatography equipped with fluorescence detector, a rapid and sensitive method for determining aflatoxins (aflatoxin B1, B2, G1 and G2) in nuts (peanuts and pistachios) was established. Under optimal conditions (35 mg F-COF, 100 mL sample solution, 3 mL min-1 as sample loading rate, pH<7, 0.2 mL acetonitrile as desorption solvent), the limits of detection for aflatoxins were 0.02-0.30 ng g-1. The linear range was 0.08-16.0 ng g-1 and the recoveries of the F-COF-based method were 83.5-114 % with relative standard deviations less than 8.0 %.

Accessing gold p-acid reactivity under electrochemical anode oxidation (EAO) through oxidation relay.

The gold π-acid activation under electrochemical conditions is achieved. While EAO allows easy access to gold(III) intermediates over alternative chemical oxidation under mild conditions, the reported examples so far are limited to coupling reactions due to the rapid AuIII reductive elimination. Using aryl hydrazine-HOTf salt as precursors, the π-activation reaction mode was realized through oxidation relay. Both alkene and alkyne di-functionalization were achieved with excellent functional group compatibility and regioselectivity, which extended the versatility and utility of electrochemical gold redox chemistry for future applications.

Triazole-modified Ru-carbene complexes: A valid olefin metathesis pre-catalyst for dynamic covalent chemistry via C=C bond formation.

The 1,2,3-triazole coordinated ruthenium carbene complexes (TA-Ru) were reported for the first time as a new class of modified Grubbs catalyst to achieve challenging olefin metathesis at higher temperatures without catalyst decomposition. Previously reported N-tethered Ru-carbene complexes all suffered from rapid cis/trans isomerization, causing significantly reduced catalyst reactivity. These new TA-Ru complexes hold the active trans-dichloro conformation even at 80 °C, allowing effective olefin metathesis for challenging substrates. With this new TA-Ru catalyst, cross-metathesis (CM), ring-closing metathesis (RCM) and dynamic covalent chemistry (DCvC) were achieved. Excitingly, the reactivity of TA-Ru prevails all previously reported N-coordinated Ru-carbene precatalysts, Grubbs II, and Hoveyda-Grubbs, making the TA-Ru a transformative catalytic system in olefin catalysis.

Effect of peach gum polysaccharide on the rheological and 3D printing properties of gelatin-based functional gummy candy.

Excellent 3D printing materials must exhibit good extrudability and supportability, but these two characteristics are often contradictory. In this study, peach gum polysaccharide (PGP) was added to gelatin to prepare a 3D-printed functional gummy candy encapsulating curcumin. Rheology tests indicated that adding PGP could effectively improve the apparent viscosity and thermal stability and consequently improve the 3D printability and supportability of the products. When PGP addition was 6 %, the printing accuracy was higher than 90 %. Texture and microstructure analysis further revealed that PGP addition promoting a dense gel structure formed and the water holding capacity and supportability of gel materials were enhanced. Furthermore, the in vitro gastrointestinal digestion tests showed that after 6 h of simulated gastrointestinal fluid digestion, the retention rate of curcumin was nearly 80 %. The above results indicated that the composite gel of PGP and gelatin is a good 3D printing base material for nutrient delivery.

The impact of mulberry leaf extract at three different levels on reducing the glycemic index of white bread.

In this study, the influences of mulberry leaf extract (MLE) addition on the physicochemical properties including the specific volume, texture and sensory features of white bread (WB) were evaluated by the sensory analysis technology. A double-blind, randomised, repeat-measure design was used to study the impact of MLE addition on the postprandial blood glucose response as well as the satiety index of WB. Results showed that the addition of MLE showed no significant effects on the physicochemical properties of WB except for the slight changes of color and bitterness. The addition of MLE significantly reduced the total blood glucose rise after ingestion of WB over 120 minutes, and reduced the GI value of WB in a dose-effect relationship. When the concentration of MLE reached 1.5 g per 100 g available carbohydrate, the GI value of WB could be reduced from 77 to 43. This study provides important information in terms of the appropriateness of MLE when added to more complex real food, the dose-dependent relationship could supply a reference for the application of MLE.

Identifying Ferroptosis-Related Genes Associated with Weight Loss Outcomes and Regulation of Adipocyte Microenvironment.

SCOPE: The study is about the influence of ferroptosis-related genes combined with the immune microenvironment exerted on weight control outcomes and systematic analysis. METHODS AND RESULTS: Subcutaneous adipose tissue (sWAT) samples from 11 subjects with good outcome and 10 subjects with poor outcome in weight management are obtained from the Gene Expression Omnibus database. The results are validated in vivo in animal models with different weight loss outcomes. The CIBERSORT algorithm is used to evaluate the differences in immune cell infiltration in each sample. Patients with poor outcome have higher levels of ferroptosis in the adipose tissue. Remarkable differences in cytokine production, nuclear factor kappa-B(NF-κB) transcription factor activity, leukocyte migration involved in the inflammatory response, and other biological processes are also observed compared to that in the well-controlled group. Aldo-keto reductase family 1-member C1(AKR1C1), nuclear receptor coactivator 4(NCOA4), and glutamate-cysteine ligase catalytic subunit(GCLC) are identified as core predictive markers and their expression patterns are confirmed in animal models. CONCLUSIONS: Ferroptosis and its mediated inflammation play an important role in long-term weight control, and analyses of the role of ferroptosis-related genes(FRGs) in weight control may provide new potential therapeutic targets for long-term weight control. Anti-inflammatory diets that mitigate inflammatory responses and affect ferroptosis may be considered in the future to improve weight control.

Homoharringtonine-Based Induction Regimen Improved the Remission Rate and Survival Rate in Chinese Childhood AML: A Report From the CCLG-AML 2015 Protocol Study.

PURPOSE: Homoharringtonine (HHT) is commonly used for the treatment of Chinese adult AML, and all-trans retinoic acid (ATRA) has been verified in acute promyelocytic leukemia (APL). However, the efficacy and safety of HHT-based induction therapy have not been confirmed for childhood AML, and ATRA-based treatment has not been evaluated among patients with non-APL AML. PATIENTS AND METHODS: This open-label, multicenter, randomized Chinese Children's Leukemia Group-AML 2015 study was performed across 35 centers in China. Patients with newly diagnosed childhood AML were first randomly assigned to receive an HHT-based (H arm) or etoposide-based (E arm) induction regimen and then randomly allocated to receive cytarabine-based (AC arm) or ATRA-based (AT arm) maintenance therapy. The primary end points were the complete remission (CR) rate after induction therapy, and the secondary end points were the overall survival (OS) and event-free survival (EFS) at 3 years. RESULTS: We enrolled 1,258 patients, of whom 1,253 were included in the intent-to-treat analysis. The overall CR rate was significantly higher in the H arm than in the E arm (79.9% v 73.9%, P = .014). According to the intention-to-treat analysis, the 3-year OS was 69.2% (95% CI, 65.1 to 72.9) in the H arm and 62.8% (95% CI, 58.7 to 66.6) in the E arm (P = .025); the 3-year EFS was 61.1% (95% CI, 56.8 to 65.0) in the H arm and 53.4% (95% CI, 49.2 to 57.3) in the E arm (P = .022). Among the per-protocol population, who received maintenance therapy, the 3-year EFS did not differ significantly across the four arms (H + AT arm: 70.7%, 95% CI, 61.1 to 78.3; H + AC arm: 74.8%, 95% CI, 67.0 to 81.0, P = .933; E + AC arm: 72.9%, 95% CI, 65.1 to 79.2, P = .789; E + AT arm: 66.2%, 95% CI, 56.8 to 74.0, P = .336). CONCLUSION: HHT is an alternative combination regimen for childhood AML. The effects of ATRA-based maintenance are comparable with those of cytarabine-based maintenance therapy.

Accessing Gold π-Acid Reactivity under Electrochemical Anode Oxidation (EAO) through Oxidation Relay.

The gold π-acid activation under electrochemical condition is achieved for the first time. While EAO allowing easy access to gold(III) intermediates over alternative chemical oxidation under mild conditions, the reported examples so far limited to coupling reactions due to the rapid AuIII reductive elimination. Using aryl hydrazine-HOTf salt as precursors, the π-activation reaction mode was realized through oxidation relay. Both alkene and alkyne di-functionalization were achieved with excellent functional group compatibility and regioselectivity, which extended the versatility and utility of electrochemical gold redox chemistry for future applications to come.