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As an important kind of emerging heterogeneous catalyst for sustainable chemical processes, supported metal cluster (SMC) catalysts have received great attention for their outstanding activity; however, the easy aggregation of metal clusters due to their migration along the substrate’s surface usually deteriorates their activity and even causes catalyst failure during cycling. Herein, stable Pt nanoclusters (NCs, ∼1.06 nm) are homogeneously confined in the uniform spherical mesopores of mesoporous titania (mpTiO2) by the interaction between Pt NCs and metal oxide pore walls made of polycrystalline anatase TiO2. The obtained Pt-mpTiO2exhibits excellent stability with well-retained CO conversion (∼95.0%) and Pt NCs (∼1.20 nm) in the long term water–gas shift (WGS) reaction. More importantly, the Pt-mpTiO2displays an unusual increasing activity during the cyclic catalyzing WGS reaction, which was found to stem from the in situgeneration of interfacial active sites (Ti3+-Ov-Ptδ+) by the reduction effect of spillover hydrogen generated at the stably supported Pt NCs. The Pt-mpTiO2catalysts also show superior performance toward the selective hydrogenation of furfural to 2-methylfuran. This work discloses an efficient and robust Pt-mpTiO2catalyst and systematically elucidates the mechanism underlying its unique catalytic activity, which helps to design stable SMC catalysts with self-enhancing interfacial activity in sustainable heterogeneous catalysis.

• A new carbon-coated MoS 2 /N-doped carbon nanotubes composite has been designed. • The in-situ conversion growth strategy proposed is simple, and high-efficient. • The C-MoS 2 /NCNTs electrode prepared delivers a remarkable sodium storage behavior. • The unique structural merits contribute to the superior electrochemical performance. Layered structure MoS 2 nanosheets have shown great potential for energy storage applications. However, the methodology for elaborately controllable growth of MoS 2 onto carbonaceous matrix for promoting the electrochemical performance is highly desirable. Herein, a high-effective, all-in-one in-situ conversion growth strategy has been proposed to construct a stable sandwich-type nanostructure. The formation of the optimized C-MoS 2 /NCNTs product undergoes a dissolution-recrystallization process, in which ultrathin carbon layer-coated MoS 2 nanosheets densely assembled onto the surface of polyimide (PI) derived N-doped carbon nanotubes (CNTs). Theoretical simulation reveals that MoS 2 nanosheets possessing an expanded interlayer spacing of 0.92 nm can greatly reduce the barrier energy of Na ions mitigation. Accordingly, the as-made C-MoS 2 /NCNTs anode delivers superior cycling stability (82% capacity retention after 400 cycles at 1 A g−1) and rate performance (348 mAh g−1 at 2 A g−1). The results demonstrate that the expanded MoS 2 interlayer distance, ultrathin outer carbon coating, and N-doped CNTs matrix together accounts for the outstanding sodium storage capability for the C-MoS 2 /NCNTs electrode. [Display omitted] [ABSTRACT FROM AUTHOR]

• A stable and highly conductive 1D/2D heterostructure has been constructed. • The as-synthesized C-MoS 2 /CNTs-Ti 3 C 2 composite has multiple structural merits. • The quaternary C-MoS 2 /CNTs-Ti 3 C 2 composite exhibit an excellent sodium storage. The exploration of advanced MoS 2 -based electrode materials overcoming their inherent low conductivity and large volume changes is of importance for next-generation energy storage. In this work, we report a simple and high-efficient one-pot hydrothermal approach to prepare a unique and stable 1D/2D heterostructure. In the architecture, ultrathin carbon layer-coated MoS 2 nanosheets with large expanded interlayer of 1.02 nm are vertically grown onto the Ti 3 C 2 MXene and cross-linked carbon nanotubes (CNTs), giving rise to a highly conductive 3D network. The interlayer expanded MoS 2 nanosheets can greatly facilitate the Na ions/electrons transmission. Meanwhile, the N-doped 1D/2D CNTs-Ti 3 C 2 matrix can be used as a strong mechanical support to well relieve the large volume expansion upon cycles. As a combination result of several advantages, the developed quaternary C-MoS 2 /CNTs-Ti 3 C 2 composite anode shows an excellent sodium storage performance (562 mA h g−1 at 100 mA g−1 after 200 cycles) and rate capability (475 mA h g−1 at 2000 mA g−1). The density functional theory calculations further prove that the full combination of layer-expanded MoS 2 nanosheets and N-doped Ti 3 C 2 matrix can significantly enhance the adsorption energy of Na ions, further resulting in the enhancement of sodium storage capabilities. [ABSTRACT FROM AUTHOR]

Si-based materials have shown great potential as lithium-ion batteries (LIBs) anodes due to their natural reserves and high theoretical capacity. However, the large volume changes during cycles and poor conductivity of Si lead to rapid capacity decay and poor cycling stability, ultimately limiting their commercial applications. Herein, we have skillfully utilized the microporous MCM-22 zeolite as the unique silicon source to produce porous Si (pSi) sheets by a simple magnesiothermic reduction, followed by a carbon coating and further Ti3C2TxMXene assembly, obtaining the ternary pSi@NC@TNSs composite. In the design, porous Si sheets provide more active sites and shorten Li-ion transport paths for electrochemical reactions. The N-doped carbon (NC) layer serves as a bonding layer to couple pSi and Ti3C2Tx. The conductive network formed by 2D Ti3C2Txand medium NC layer effectively enhances the overall charge transport of the electrode material, and helps to stabilize the electrode structure. Therefore, the as-made pSi@NC@TNSs anode delivers an improved lithium storage performance, exhibiting a high reversible capacity of 925 mAh/g at 0.5 A/g after 100 cycles. This present strategy provides an effective way towards high-performance Si-based anodes for LIBs.

Metal–organic frameworks (MOFs) are important photocatalytic materials for H2production. To clarify the structure–function relationship and improve the photocatalytic activity, herein we explored a series of porphyrin-based zirconium MOFs (PCN-H2/Ptx:y, where x:y= 4:1, 3:2, 2:3, and 0:1) containing different ratios of H2TCPP and PtIITCPP [TCPP = tetrakis(4-carboxyphenyl)porphyrinate] as isostructural ligands and Zr6clusters as nodes. Under visible-light irradiation, PCN-H2/Pt0:1shows the highest average H2evolution reaction rate (351.08 μmol h–1g–1), which decreases along with lowering of the ratio of PtIITCPP in the PCN-H2/Ptx:yseries. The differences in photocatalytic activity are attributed to more uniformly dispersed Pt2+ions in PCN-H2/Pt0:1, which promotes charge transfer from porphyrins (photosensitizers) to PtIIions (catalytic centers), leading to efficient charge separation in the MOF materials. The bifunctional MOFs with photosensitizers and catalytic centers provide new insight for the design and application of porphyrin-based photocatalytic systems for visible-light-driven H2production.

Exploring Si-based anode materials with high electrical conductivity and electrode stability is crucial for high-performance lithium-ion batteries (LIBs). Herein, we propose the fabrication of a Si-based composite where Si porous nanospheres (Si p-NSs) are tightly wrapped by Ti3C2Tx(Txstands for the surface groups such as −OH, −F) MXene nanosheets (TNSs) through an interfacial assembly strategy. The TNSs as a conductive and robust tight of the Si p-NSs can effectively improve electron transport and electrode stability, as revealed by substantial characterizations and mechanical simulations. Moreover, the TNSs with rich surface groups enable strong interfacial interactions with the Si p-NS component and a pseudocapacitive behavior, beneficial for fast and stable lithium storage. Consequently, the Si p-NS@TNSs electrode with a high Si content of 85.6% exhibits significantly enhanced battery performance compared with the Si p-NSs electrode such as high reversible capacity (1154 mAh g–1at 0.2 A g–1), long cycling stability (up to 2000 cycles with a 0.026% capacity decay rate per cycle), and excellent rate performances. Notably, the Si p-NS@TNSs electrode-based LIB full cell delivers a high energy uptake of 405 Wh kg–1, many-times higher than that of the Si p-NSs full cell. This work offers a strategy to develop advanced Si-based anode materials with desirable properties for high-performance LIBs.

N-doped TiO2mesoporous nanostructure has been synthesized viaa facile CQDs-regulated hydrothermal route. The resulting TiO2product shows the large surface area, high conductivity, abundant mesopores, and excellent sodium storage capability.

Effect of different Cu precursors in preparing Cu@MOR catalysts for direct conversion of metane to methanol was investigated.

A facile one-pot hydrothermal approach has been developed for the preparation of mesoporous silica nanoparticles (MSNs) with hierarchical pore structure. The PEI-modified MSNs exhibit an improved adsorption capacity for CO2capture.

TiO2has been widely studied as one of the most promising anode materials for lithium-ion batteries (LIBs) due to good structural stability and small volume changes. However, its applications are still greatly affected by its poor electrical conductivity. In this work, ultrasmall TiO2quantum dots (QDs) are firmly grown onto 2D Ti3C2Txnanosheets (A-TiO2/Ti3C2Tx), benefiting from the positive regulation of (3-aminopropyl) triethoxysilane (APTES). Interestingly, SiO2nanoparticles produced by the hydrolysis of APTES can strengthen the strong coupling of TiO2QDs with Ti3C2Tx, thereby enhancing the structural integrity of the composite. As expected, the A-TiO2/Ti3C2Txcomposite demonstrates an exceptional lithium storage performance, achieving a high capacity of 425.4 mAh/g for 400 cycles at 0.1 A/g, and an outstanding long-term cycling stability. In-situelectrochemical impedance spectroscopy and theoretical analysis unconver that the superior lithium storage performance is attributed to its unique heterostructure and in-situN doping derived from APTES, which not only reduces the Li+adsorption energy, but also gives the fast charge transfer dynamics.

TiNb2O7has been emerged as one of the most promising electrode materials for high-energy lithium-ion batteries. However, limited by the slow electron/ion transport kinetics, and insufficient active sites in the bulk structure, the TiNb2O7electrode still suffers from unsatisfactory lithium storage performance. Herein, we demonstrate a spatially confined strategy toward a novel TiNb2O7-NMC/MXene composite through a triblock copolymer-directed one-pot solvothermal route, where TiNb2O7quantum dots with a particle size of 2–3 nm are evenly embedded into N-doped mesoporous carbon (NMC) and Ti3C2TXMXene. Impressively, the as-prepared TiNb2O7-NMC/MXene anode exhibits a high reversible capacity (486.2 mAh g−1at 0.1 A g−1after 100 cycles) and long cycle lifespan (363.4 mAh g−1at ss1 A g−1after 500 cycles). Both experimental and theorical results further demonstrate that such a superior lithium storage performance is mainly ascribed to the synergistic effect among 0D TiNb2O7quantum dots, 2D Ti3C2TXMXene nanosheets, and N-doped mesoporous carbon. The strategy presented also opens up new horizon for space-confined preparation of high-performance electrode materials.

The development of a high-rate SiO lithium-ion battery anode is seriously limited by its low intrinsic conductivity, sluggish interfacial charge transfer (ICT), and unstable dynamic interface. To tackle the above issues, interfacial encapsulation engineering for effectively regulating the interfacial reaction and thus realizing a stable solid electrolyte interphase is significantly important. Hybrid coating, which aims to enhance the coupled e–/Li+transport via the employment of dual layers, has emerged as a promising strategy. Herein, we construct a hybrid MXene-graphene oxide (GO) coating layer on the SiO microparticles. In the design, Ti3C2TxMXene acts as a “bridge”, which forms a close covalent connection with SiO and GO through Ti–O–Si and Ti–O–C bonds, respectively, thus greatly reducing the ICT resistance. Moreover, the Ti3C2Txwith rich surface groups (e.g., –OH, –F) and GO outer layers with an intertwined porous framework synergistically enable the pseudocapacitance dominated behavior, which is beneficial for fast lithium-ion storage. Accordingly, the as-made Si@MXene@GO anode exhibits considerably reinforced lithium-ion storage performance in terms of superior rate performance (1175.9 mA h g–1at 5 A g–1) and long cycling stability (1087.6 mA h g–1capacity retained after 1000 cycles at 2.0 A g–1). In-depth interfacial chemical composition analysis further reveals that an inorganically rich interphase with a gradient distribution of LiF and Li2O formed at the electrolyte/anode interface ensures mechanical stability during repeated cycles. This work paves a feasible way for maximizing the potential of SiO anodes toward fast-charging lithium-ion batteries.

Introduction:Ventoclax-based combinations have emerged as a new standard of care for patients with acute myeloid leukemia (AML) who are not suitable for intense chemotherapy. Not all patients respond to these treatments, and those who do may relapse. MDM2 inhibitors are promising therapeutics for treating TP53 wild-type tumors, including most de novo AML cases, with numerous compounds currently in pre-clinical and clinical evaluation. However, clinical trials of MDM2 inhibitors have shown modest and variable clinical activity. Functional genomic data showed that monocytic leukemia (FAB M4/M5) is resistant to venetoclax-based therapies and MDM2 inhibitors. Notably, venetoclax and an MDM2 inhibitor, idasanutlin, demonstrated a strong positive correlation in the Beat AML cohort.

Chronic neutrophilic leukemia (CNL), atypical chronic myeloid leukemia (aCML), and myelodysplastic/myeloproliferative neoplasms, unclassifiable (MDS/MPN-U) are a group of rare and heterogeneous myeloid disorders. There is strong morphologic resemblance among these distinct diagnostic entities as well as a lack of specific molecular markers and limited understanding of disease pathogenesis, which has made diagnosis challenging in certain cases. The treatment has remained empirical, resulting in dismal outcomes. We, therefore, performed whole-exome and RNA sequencing of these rare hematologic malignancies and present the most complete survey of the genomic landscape of these diseases to date. We observed a diversity of combinatorial mutational patterns that generally do not cluster within any one diagnosis. Gene expression analysis reveals enrichment, but not cosegregation, of clinical and genetic disease features with transcriptional clusters. In conclusion, these groups of diseases represent a continuum of related diseases rather than discrete diagnostic entities.

The conceptual design of yolk-shell structured Si/C composites is considered to be an effective way to improve the recyclability and conductivity of Si-based anode materials. Herein, a new type of yolk-shell structured Si/C composite (denoted as TSC-PDA-B) has been intelligently designed by rational engineering and precise control. In the novel structure, the multiple Si nanoparticles with small size are successfully encapsulated into the porous carbon shells with double layers benefiting from the strong etching effect of HF. The TSC-PDA-B product prepared is evaluated as anode materials for lithium-ion batteries (LIBs). The TSC-PDA-B product exhibits an excellent lithium storage performance with a high initial capacity of 2108 mAh g−1at a current density of 100 mA g−1and superior cycling performance of 1113 mAh g−1over 200 cycles. The enhancement of lithium storage performance may be attributed to the construction of hybrid structure including small Si nanoparticles, high surface area, and double carbon shells, which can not only increase electrical conductivity and intimate electrical contact with Si nanoparticles, but also provide built-in buffer voids for Si nanoparticles to expand freely without damaging the carbon layer. The present findings can provide some scientific insights into the design and the application of advanced Si-based anode materials in energy storage fields.

The implementation of targeted therapies for acute myeloid leukaemia (AML) has been challenging because of the complex mutational patterns within and across patients as well as a dearth of pharmacologic agents for most mutational events. Here we report initial findings from the Beat AML programme on a cohort of 672 tumour specimens collected from 562 patients. We assessed these specimens using whole-exome sequencing, RNA sequencing and analyses of ex vivo drug sensitivity. Our data reveal mutational events that have not previously been detected in AML. We show that the response to drugs is associated with mutational status, including instances of drug sensitivity that are specific to combinatorial mutational events. Integration with RNA sequencing also revealed gene expression signatures, which predict a role for specific gene networks in the drug response. Collectively, we have generated a dataset—accessible through the Beat AML data viewer (Vizome)—that can be leveraged to address clinical, genomic, transcriptomic and functional analyses of the biology of AML.

Carbons are considered less favorable for postcombustion CO2capture because of their low affinity toward CO2, and nitrogen doping was widely studied to enhance CO2adsorption, but the results are still unsatisfactory. Herein, we report a simple, scalable, and controllable strategy of tethering potassium to a carbon matrix, which can enhance carbon–CO2interaction effectively, and a remarkable working capacity of ca. 4.5 wt % under flue gas conditions was achieved, which is among the highest for carbon-based materials. More interestingly, a high CO2/N2selectivity of 404 was obtained. Density functional theory calculations evidenced that the introduced potassium carboxylate moieties are responsible for such excellent performances. We also show the effectiveness of this strategy to be universal, and thus, cheaper precursors can be used, holding great promise for low-cost carbon capture from flue gas.

With the accelerated penetration of the global electric vehicle market, the demand for fast charging lithium-ion batteries (LIBs) that enable improvement of user driving efficiency and user experience is becoming increasingly significant. Robust ion/electron transport paths throughout the electrode have played a pivotal role in the progress of fast charging LIBs. Yet traditional graphite anodes lack fast ion transport channels, which suffer extremely elevated overpotential at ultrafast power outputs, resulting in lithium dendrite growth, capacity decay, and safety issues. In recent years, emergent multiscale porous anodes dedicated to building efficient ion transport channels on multiple scales offer opportunities for fast charging anodes. This review survey covers the recent advances of the emerging multiscale porous anodes for fast charging LIBs. It starts by clarifying how pore parameters such as porosity, tortuosity, and gradient affect the fast charging ability from an electrochemical kinetic perspective. We then present an overview of efforts to implement multiscale porous anodes at both material and electrode levels in diverse types of anode materials. Moreover, we critically evaluate the essential merits and limitations of several quintessential fast charging porous anodes from a practical viewpoint. Finally, we highlight the challenges and future prospects of multiscale porous fast charging anode design associated with materials and electrodes as well as crucial issues faced by the battery and management level.

Highlights:

The synthetic strategies and fundamental mechanisms of various asymmetric carbon- and silica-based nanomaterials were systematically summarized.

The advantages of asymmetric structure on their related applications were clarified by some representative applications of asymmetric carbon- and silica-based nanomaterials.

The future development prospects and challenges of asymmetric carbon- and silica-based nanomaterials were proposed. Abstract: Carbon- and silica-based nanomaterials possess a set of merits including large surface area, good structural stability, diversified morphology, adjustable structure, and biocompatibility. These outstanding features make them widely applied in different fields. However, limited by the surface free energy effect, the current studies mainly focus on the symmetric structures, such as nanospheres, nanoflowers, nanowires, nanosheets, and core–shell structured composites. By comparison, the asymmetric structure with ingenious adjustability not only exhibits a larger effective surface area accompanied with more active sites, but also enables each component to work independently or corporately to harness their own merits, thus showing the unusual performances in some specific applications. The current review mainly focuses on the recent progress of design principles and synthesis methods of asymmetric carbon- and silica-based nanomaterials, and their applications in energy storage, catalysis, and biomedicine. Particularly, we provide some deep insights into their unique advantages in related fields from the perspective of materials’ structure–performance relationship. Furthermore, the challenges and development prospects on the synthesis and applications of asymmetric carbon- and silica-based nanomaterials are also presented and highlighted.

Brassica species, including crops such as cabbage, turnip and oilseed, display enormous phenotypic variation. Brassica genomes have all undergone a whole-genome triplication (WGT) event with unknown effects on phenotype diversification. We resequenced 199 Brassica rapa and 119 Brassica oleracea accessions representing various morphotypes and identified signals of selection at the mesohexaploid subgenome level. For cabbage morphotypes with their typical leaf-heading trait, we identified four subgenome loci that show signs of parallel selection among subgenomes within B. rapa, as well as four such loci within B. oleracea. Fifteen subgenome loci are under selection and are shared by these two species. We also detected strong subgenome parallel selection linked to the domestication of the tuberous morphotypes, turnip (B. rapa) and kohlrabi (B. oleracea). Overall, we demonstrated that the mesohexaploidization of the two Brassica genomes contributed to their diversification into heading and tuber-forming morphotypes through convergent subgenome parallel selection of paralogous genes.

Abstract

The application of several titanosilicates to the oxidation of aromatic sulfur compounds such as thiophene, benzothiophene, dibenzothiophene, and 4,6‐dimethyldibenzothiophene with H2O2under mild conditions is reported. Superior to other titanosilicates, Ti‐MWW demonstrates a higher activity for the oxidation of 4,6‐dimethyldibenzothiophene owing to the unique pore structure of the MWW topology. The effects of solvent, temperature, catalyst amount, and H2O2/S ratio on the oxidation of 4,6‐dimethyldibenzothiophene over this catalyst are studied in detail. The catalyst is also applied to the oxidative desulfurization of commercial diesel. The sulfur compounds in the commercial diesel were oxidized to the corresponding sulfones, which could be readily extracted by acetonitrile, resulting in a maximum sulfur removal of 88 % .

A unique pumpkin-like MoP-MoS2@SNC composite has been prepared via a facile hydrothermal route and subsequent phosphorization process, which shows the enhanced potassium storage capability.

A much greener synthesis method is discovered for the synthesis of 3,4-epoxytetrahydrofuran (ETHF), an important synthetic intermediate for stereo-controllable synthesis of complex organic compounds. 3,4-ETHF is synthesized with a conversion >95% and a selectivity >99% through a heterogeneous epoxidation of 2,5-dihydrofuran (DHF) with hydrogen peroxide in the liquid phase over a novel titanosilicate catalyst, Ti-MWW.

To accelerate the commercial implementation of high-energy batteries, recent research thrusts have turned to the practicality of Si-based electrodes. Although numerous nanostructured Si-based materials with exceptional performance have been reported in the past 20 years, the practical development of high-energy Si-based batteries has been beset by the bias between industrial application with gravimetrical energy shortages and scientific research with volumetric limits. In this context, the microscale design of Si-based anodes with densified microstructure has been deemed as an impactful solution to tackle these critical issues. However, their large-scale application is plagued by inadequate cycling stability. In this review, we present the challenges in Si-based materials design and draw a realistic picture regarding practical electrode engineering. Critical appraisals of recent advances in microscale design of stable Si-based materials are presented, including interfacial tailoring of Si microscale electrode, surface modification of SiOxmicroscale electrode, and structural engineering of hierarchical microscale electrode. Thereafter, other practical metrics beyond active material are also explored, such as robust binder design, electrolyte exploration, prelithiation technology, and thick-electrode engineering. Finally, we provide a roadmap starting with material design and ending with the remaining challenges and integrated improvement strategies toward Si-based full cells.

Carbonaceous nanomaterials with porous structure have become the highly promising anode materials for potassium-ion batteries (PIBs) due to their abundant resources, low-cost, and excellent conductivity. Nevertheless, the sluggish reaction kinetics and inferior cycling life caused by the large radius of K ions severely restrict their commercial development. Herein, B,N co-doped hierarchically porous carbon nanosheets (BNPC) are achieved viaa facile template-assisted route, followed by a simple one-step carbonization process. The resultant BNPC possesses a unique porous structure, large surface area, and high-level B,N co-doping. The structural features endows it with remarkable potassium storage performances, which delivers a high reversible capacity (242.2 mAh/g at 100 mA/g after 100 cycles), and long cycling stability (123.1 mAh/g at 2000 mA/g and 62.9 mAh/g at 5000 mA/g after 2000 cycles, respectively). Theoretical simulations further validate that the rich B doping into N-modified carbon configuration can greatly boost the potassium storage capability of the BNPC anode.

Hybrid MoS2/C nanostructures have shown great promise as an ideal anode for lithium-ion batteries (LIBs) owing to the improved conductivity and electrochemical performance. Nevertheless, if only one side of MoS2particles is covered by conductive carbon layer, other exposed side is still low conductivity. Meanwhile, the structure of electrodes is relatively not robust. Herein, an effective structural engineering strategy has been proposed for achieving a new type of polypyrrole-derived carbon nanotubes@MoS2@carbon (PCN@MoS2@C) sandwiched architecture via a facile one-pot hydrothermal process. When utilized as anodes for lithium storage, the resulting MoS2/C hybrid exhibits a large specific capacity of 1079 mA h g−1at 0.1 A g−1and high coulombic efficiency of above 99.0% over 200 cycles, showing a superior cycling stability and reversibility. The density functional theory (DFT) calculations further demonstrate that ultrathin MoS2nanosheets with an expanded interlayer distance of 0.98 nm have more accessible space, lower transfer resistance, and faster diffusion kinetics of Li ions. The great improvement in electrochemical properties is mainly ascribed to the design of peculiar hybrid architecture, and the collaborative effect between active MoS2nanosheets and two different conductive carbon layers. This work sheds a new light on the rational design of advanced electrode materials with boosted performance and stable structural stability.

In this paper, a method for the determination of formaldehyde in carbon-coated air purifying material by ultraviolet spectrophotometry was established. The test determined the detection limit, lower limit of determination, precision and accuracy of the method. When the sampling quality is 2.0g, the detection limit of the method is 0.0412ug, the recovery is 98.4%[?]105.8%, and the precision RSD is 2.646% [?] 3.894%. The results show that this method is suitable for the determination of formaldehyde in carbon-coated air purifying material.

The free formaldehyde in carbon-coated air purifying material was determined by water extraction method. The effects of solid-liquid ratio, extraction time and extraction temperature on the content of free formaldehyde in carbon-coated air purifying material were studied. In this paper, orthogonal tests and single factor tests were designed, and the optimal extraction conditions were 1:40 solid-liquid ratio, 90 min extraction time and 40 degC extraction temperature. Under this extraction condition, the relative standard deviation (n = 8) of the repeated test is 0.80%, and the recovery rate is 90%-100%, which indicates that the analytical method for determining the free formaldehyde in carbon-coated air purifying material by water extraction method is feasible.

Druker: Beta Cat: Membership on an entity's Board of Directors or advisory committees; Fred Hutchinson Cancer Research Center: Research Funding; McGraw Hill: Patents & Royalties; Vivid Biosciences: Membership on an entity's Board of Directors or advisory committees; Oregon Health & Science University: Patents & Royalties; Bristol-Meyers Squibb: Research Funding; GRAIL: Consultancy, Membership on an entity's Board of Directors or advisory committees; ARIAD: Research Funding; Third Coast Therapeutics: Membership on an entity's Board of Directors or advisory committees; Gilead Sciences: Consultancy, Membership on an entity's Board of Directors or advisory committees; Monojul: Consultancy; Novartis Pharmaceuticals: Research Funding; Millipore: Patents & Royalties; Leukemia & Lymphoma Society: Membership on an entity's Board of Directors or advisory committees, Research Funding; ALLCRON: Consultancy, Membership on an entity's Board of Directors or advisory committees; Aileron Therapeutics: Consultancy; Patient True Talk: Consultancy; Cepheid: Consultancy, Membership on an entity's Board of Directors or advisory committees; Henry Stewart Talks: Patents & Royalties; Celgene: Consultancy; Amgen: Membership on an entity's Board of Directors or advisory committees; MolecularMD: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Blueprint Medicines: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Aptose Therapeutics: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Majeti:BioMarin: Consultancy; Forty Seven, Inc: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Tyner:Incyte: Research Funding; AstraZeneca: Research Funding; Janssen: Research Funding; Takeda: Research Funding; Leap Oncology: Equity Ownership; Seattle Genetics: Research Funding; Genentech: Research Funding; Gilead: Research Funding; Syros: Research Funding; Aptose: Research Funding; Agios: Research Funding.

BCL2 is an antiapoptotic protein commonly expressed in hematologic malignancies. Overexpression of BCL-2 is a poor prognostic factor in acute myeloid leukemia (AML). Venetoclax (ABT-199) is a highly selective BCL2 inhibitor that can induce cell death in multiple leukemia cell lines. Recently, venetoclax received an FDA breakthrough therapy designation for use in combination with hypomethylating agents in treatment-naïve patients with AML who are unfit for intensive chemotherapy. However, venetoclax was only modestly effective as monotherapy in relapsed/refractory AML (19% CR/CRi). The aim of the current study is to integrate genomic and functional screen data to identify biomarkers to predict venetoclax sensitivity and resistance in AML, and to identify potential venetoclax combination treatment strategies.

Purpose:Chronic neutrophilic leukemia (CNL), chronic myelomonocytic leukemia (CMML), atypical myeloid leukemia (aCML), and unclassified myeloproliferative neoplasms (unMPN) are rare entities of myeloproliferative or myelodysplastic/myeloproliferative (MDS/MPN) syndromes. Due to poorly defined molecular mechanisms, these diseases have been, until now, diagnosed based on morphology and exclusionary criteria and treated empirically, resulting in dismal outcomes. Recent application of next generation sequencing has shed light on the genetic mechanisms of CNL/aCML/CMML/MPN-U. In particular, Maxson et al. and others have shown that CSF3R membrane proximal and transmembrane mutations are present in 83-89% of CNL and 3.3-44% of aCML patients, and expression of CSF3R membrane proximal mutants is sufficient to recapitulate the clinical features (mature granulocyte accumulation) of CNL in a mouse model. This has led to revision of the WHO diagnostic criteria for CNL, enabling a more accurate diagnosis and facilitating the development of targeted treatment for this disease. Aside from the CSF3R driver mutations, few recurrent signaling pathway mutations have been characterized in this group of diseases that could serve as the basis for such targeted therapeutic strategies. The aim of the current study is to characterize the frequency and distribution of signaling pathway driver mutations in a large cohort of CNL/aCML/CMML/MPN-U patients with the hope of informing diagnosis, prognosis and treatment.

Activating mutations in granulocyte colony-stimulating factor receptor (CSF3R), are found in the extracellular, the membrane proximal, the transmembrane and the cytoplasmic domain of the receptor in various leukemia. To expand the spectrum of CSF3R mutations that can arise to transform Ba/F3 cells initially transfected with wild type CSF3R, we performed a spontaneous cellular transformation assay. We identified several new CSF3R activating mutations. These mutations are located in the extracellular, the membrane proximal, and the transmembrane domains of CSF3R. We further characterized that these mutations transform cells via four distinct mechanisms: (1) cysteine and disulfide bond mediated dimerization, leading to increased STAT3 activation (S581C); (2) polar, non-charged amino acid substitution at the transmembrane helix dimer interface T640, inducing increased STAT3 and ERK activation; (3) increased internalization and STAT3 activation by an E524 substitution; and (4) hydrophobic amino acid substitutions in the membrane proximal O glycosylation sites (T612, T615 and T618), leading to enhanced activation of STAT3 and ERK. Furthermore, we showed that the distinct signaling activation is related to different localization of CSF3R mutants. To this end, we have expanded the region of the CSF3R extracellular and transmembrane domain in which missense mutations exhibit leukemogenic capacity and further elucidated the mechanistic underpinnings that underlie distinct signaling activation and leukemogenic mechanisms. Cumulatively, these findings will facilitate improved evaluation of the biological and clinical relevance of CSF3R mutations identified in patients.

No relevant conflicts of interest to declare.

An increasing number of CSF3R cytoplasmic domain truncation (nonsense and frameshift) and missense mutations are being identified with the wide application of next generation sequencing (NGS) to leukemia patient samples. Previous studies have demonstrated oncogenic potential of some CSF3R truncation mutations seen in severe congenital neutropenia, chronic neutrophilia leukemia (CNL), and Philadelphia-negative atypical chronic neutrophilic leukemia (aCML) patients. However, full understanding of the spectrum of CSF3R cytoplasmic mutations harboring leukemogenic potential as well as the associated mechanisms of enhanced signaling remains incomplete. In the current study, we leveraged NGS data to first validate that CSF3R cytoplasmic mutations are prevalent in CNL/aCML/unclassified myeloproliferative neoplasm (8.5%, n=212) patients and to a lesser extent in AML patients (1.3%, n=378). We did not observe CSF3R cytoplasmic mutations in other hematologic malignances. Notably, 72.2% of CSF3R cytoplasmic mutations co-occur with the membrane proximal mutation, CSF3R T618I. To evaluate the leukemogenic potential of these cytoplasmic mutations, we first investigated the minimal mutated elements necessary for CSF3R leukemogenic potential. We identified that truncation mutations of the CSF3R cytoplasmic tail between T738 and Q823 all harbor leukemogenic potential. In contrast, CSF3R truncations before E700X did not respond to G-CSF and did not transform Ba/F3 cells even when combined with T618I. Truncation mutations between E700X and T738X demonstrated reduced G-CSF sensitivity, but could transform Ba/F3 cells when combined with CSF3R T618I. Surprisingly, all the cytoplasmic missense mutations (Q754A, R769H, L777F, T781I, S795R and Q823H), seen in the patient samples did not harbor leukemogenic potential. We further identified that missense mutations disrupting the di-leucine residues L776/777, S772, or ubiquitin binding lysine residues (K655, K785 and K704) demonstrated transforming capacity.

Ho: AROG Pharmaceuticals: Employment. Davis:AROG Pharmaceuticals: Employment. Ramachandran:AROG Pharmaceuticals: Employment. Cortes:ARIAD Pharmaceuticals Inc.: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Teva: Consultancy, Research Funding; BMS: Consultancy, Research Funding. Tyner:Aptose Biosciences: Research Funding; Constellation Pharmaceuticals: Research Funding; Array Biopharma: Research Funding; Janssen Pharmaceuticals: Research Funding; Incyte: Research Funding.

Introduction:Variation of the D835 residue of FLT3 occurs in ~5% of de novo AML cases and is a prominent feature of drug resistance in the setting of FLT3-ITD. Crenolanib treatment of AML patients exhibiting FLT3 D835 and/or FLT3-ITD positive tumors has yielded significant clinical responses. However, these clinical responses to single-agent crenolanib were transient, so we performed whole exome sequencing to determine the mechanisms of crenolanib resistance. Mutation of the FLT3 F691 "gatekeeper" residue is a known resistance mechanism to crenolanib and other FLT3 inhibitors in vitro. Hence, secondary mutation of FLT3 at the gatekeeper or other sites was hypothesized to be a predominant mechanism of resistance. We report that a minority of patients acquired FLT3 gatekeeper or other secondary FLT3 mutations, however, the majority of cases relapsed in the absence of additional FLT3 mutations indicating alternative mechanisms of drug resistance.

The titanosilicate of TS-1 is skillfully hydrothermally synthesized from an inorganic silica source and a cheaper structure-directing agent (SDA) of hexamethyleneimine (HMI) with the assistant of active seeds of TS-1 precursor.