Discovery of a potent Gilteritinib-based FLT3-PROTAC degrader for the treatment of Acute myeloid leukemia.

Fms-like tyrosine receptor kinase 3 (FLT3) proteolysis targeting chimeras (PROTACs) emerge as a promising approach to overcome the limitations of FLT3 inhibitors, while the development of orally bioavailable FLT3-PROTACs faces great challenges. Here, we report the rational design and evaluation of a series of Gilteritinib-based FLT3-PROTACs. Among them, B3-2 exhibited the strongest antiproliferative activity against FLT3-ITD mutant AML cells, and significantly induced FLT3-ITD protein degradation. Mechanistic investigations demonstrated that B3-2 induced FLT3-ITD degradation in a ubiquitin-proteasome-dependent manner. More importantly, B3-2 exhibited an oral bioavailability of 5.65%, and oral administration of B3-2 showed good antitumor activity in MV-4-11 xenograft models. Furthermore, B3-2 showed strong antiproliferative activity against FLT3 resistant mutations, highlighting its potential in overcoming drug resistance.

Nanomicelles Array for Ultrahigh-Density Data Storage.

High-density data storage devices based on organic and polymer materials are currently restricted by two key issues, size limitations and uniformity of memory cells. Herein, one triblock polymer is synthesized by ring-opening metathesis polymerization, where the polymer contains an electron-donor-acceptor (A1 D) segment, an electron-acceptor (A2 ) segment, and a hydrophilic segment, that shows ternary memory behavior in a conventional sandwich-type device. The polymers that have monodisperse molecular weight dispersity self-assemble into nanomicelles with a uniform size of 80 nm. Each nanomicelle is composed of an A1 DA2 -type hydrophobic core stabilized with a hydrophilic shell. Nanobowls based on conductive oxide are prepared via the template method, wherein the nanomicelles are present as independent nanoscale memory units to produce an array of micelle matrices. Investigations of the resulting nanomemory device using conductive atomic force microscopy show that the micelles exhibit a predominant semiconductor memory behavior. Compared to traditional ternary devices with a memory unit size of ≈1 mm, this innovative fabrication method based on arrayed uniform nanomicelles downscales the size of storage cells to 80 nm. Furthermore, the described system leads to a greatly enhanced storage density (>108 times over the same area), which opens up new paths for further development of ultrahigh-density data storage devices.

Development and Clinical Uses of a Mobile Application for Smart Wound Nursing Management.

OBJECTIVE: Establishing a smart platform for wound nursing management is imperative to accelerating the development of this specialty. A mobile application (app) was created based on the clinical needs of wound care to improve working efficiency and wound management, as well as enable information sharing and categorical retrieval of patient records. METHODS: Supported by the National Mobile Laboratory of China, the authors' wound care center collaborated with information technology engineers and user interface designers to establish a multidisciplinary team of experts in wound nursing information management and develop a digital app. Electronic tablets were chosen as a convenient clinical method to collect complete information in a standardized format. In the app, case records are synchronously cataloged for rapid retrieval. The app was designed such that practicing nurses could quickly learn how to use the various functions of the app. Through constant iterative optimization, the relevant functional modules have been further improved. RESULTS AND CONCLUSIONS: After a 1-year clinical trial, app functions have stabilized, fulfilling the expectations of technicians and boosting the operating efficiency of clinical practices. In comparison with traditional methods, the app allows for easy access to patient information; rapidly reviewed, synchronous cataloguing; and convenient retrieval. Further exploration is warranted.

PointVST: Self-Supervised Pre-Training for 3D Point Clouds via View-Specific Point-to-Image Translation.

The past few years have witnessed the great success and prevalence of self-supervised representation learning within the language and 2D vision communities. However, such advancements have not been fully migrated to the field of 3D point cloud learning. Different from existing pre-training paradigms designed for deep point cloud feature extractors that fall into the scope of generative modeling or contrastive learning, this paper proposes a translative pre-training framework, namely PointVST, driven by a novel self-supervised pretext task of cross-modal translation from 3D point clouds to their corresponding diverse forms of 2D rendered images. More specifically, we begin with deducing view-conditioned point-wise embeddings through the insertion of the viewpoint indicator, and then adaptively aggregate a view-specific global codeword, which can be further fed into subsequent 2D convolutional translation heads for image generation. Extensive experimental evaluations on various downstream task scenarios demonstrate that our PointVST shows consistent and prominent performance superiority over current state-of-the-art approaches as well as satisfactory domain transfer capability.

Dynamic 3D Point Cloud Sequences as 2D Videos.

Dynamic 3D point cloud sequences serve as one of the most common and practical representation modalities of dynamic real-world environments. However, their unstructured nature in both spatial and temporal domains poses significant challenges to effective and efficient processing. Existing deep point cloud sequence modeling approaches imitate the mature 2D video learning mechanisms by developing complex spatio-temporal point neighbor grouping and feature aggregation schemes, often resulting in methods lacking effectiveness, efficiency, and expressive power. In this paper, we propose a novel generic representation called Structured Point Cloud Videos (SPCVs). Intuitively, by leveraging the fact that 3D geometric shapes are essentially 2D manifolds, SPCV re-organizes a point cloud sequence as a 2D video with spatial smoothness and temporal consistency, where the pixel values correspond to the 3D coordinates of points. The structured nature of our SPCV representation allows for the seamless adaptation of well-established 2D image/video techniques, enabling efficient and effective processing and analysis of 3D point cloud sequences. To achieve such re-organization, we design a self-supervised learning pipeline that is geometrically regularized and driven by self-reconstructive and deformation field learning objectives. Additionally, we construct SPCV-based frameworks for both low-level and high-level 3D point cloud sequence processing and analysis tasks, including action recognition, temporal interpolation, and compression. Extensive experiments demonstrate the versatility and superiority of the proposed SPCV, which has the potential to offer new possibilities for deep learning on unstructured 3D point cloud sequences. Code will be released at https://github.com/ZENGYIMING-EAMON/SPCV.

Effectiveness of silver and iodine dressings on wound healing: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the effects of silver and iodine dressings on healing time, healing rate, exudate amount, pain and anti-infective efficacy. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Databases including PubMed, Cochrane Library, Embase, Web of Science and CINAHL were surveyed up to May 2024. ELIGIBILITY CRITERIA: Randomised controlled trials comparing silver and iodine dressings on wound healing in humans. DATA EXTRACTION AND SYNTHESIS: Evidence certainty was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation approach. Data extraction was done independently by two reviewers, with the risk of bias assessed using the Cochrane tool. Narrative synthesis was performed to evaluate the effects of silver and iodine dressings on healing time, healing rate, pain, exudate amount and anti-infective efficacy. Meta-analysis using Review Manager V.5.4 calculated standardised mean differences for healing time and relative risks for rate to quantify the impacts of the treatments. RESULTS: 17 studies (18 articles) were included. The meta-analysis indicated that silver dressings significantly reduced healing time compared with iodine dressings (SMD=-0.95, 95% CI -1.62 to -0.28, I2=92%, p=0.005, moderate-quality evidence), with no significant difference in enhancing healing rate (RR=1.29, 95% CI 0.90 to 1.85, I2=91%, p=0.16, low-quality evidence). Based on low-quality evidence, for exudate amount (3/17), 66.7% (2/3) of the studies favoured silver dressings over iodine in reducing exudate volume. For pain (7/17), 57.1% (4/7) of the studies reported no significant difference between silver and iodine dressings, while 42.9% (3/7) studies indicated superior pain relief with silver dressings. For anti-infective efficacy (11/13), 54.5% (6/11) of the studies showed equivalence between silver and iodine dressings, while 36.4% (4/11) suggested greater antibacterial efficacy for silver. CONCLUSION: Silver dressings, demonstrating a comparable healing rate to iodine dressings, significantly reduce healing time, suggesting their potential as a superior adjunct in wound care. PROSPERO REGISTRATION NUMBER: CRD42020199602.

Impact of the hybridization form of the coordinated nitrogen atom on the electrocatalytic water oxidation performance of copper complexes with pentadentate amine-pyridine ligands.

The field of molecular catalysts places a strong emphasis on the connection between the ligand structure and its catalytic performance. Herein, we changed the type of coordinated nitrogen atom in pentadentate amine-pyridine ligands to explore the impact of its hybridization form on the water oxidation performance of copper complexes. In the electrochemical tests, the copper complex bearing dipyridine-triamine displayed an apparently higher rate constant of 4.97 s-1, while the copper complex with tripyridine-diamine demonstrated overpotential reduction by 56 mV and better long-term electrolytic stability.

Discovery of a Novel Orally Bioavailable FLT3-PROTAC Degrader for Efficient Treatment of Acute Myeloid Leukemia and Overcoming Resistance of FLT3 Inhibitors.

Fms-like tyrosine receptor kinase 3 (FLT3) proteolysis-targeting chimeras (PROTACs) represent a promising approach to eliminate the resistance of FLT3 inhibitors. However, due to the poor druggability of PROTACs, the development of orally bioavailable FLT3-PROTACs faces great challenges. Herein, a novel orally bioavailable FLT3-ITD degrader A20 with excellent pharmacokinetic properties was discovered through reasonable design. A20 selectively inhibited the proliferation of FLT3-ITD mutant acute myeloid leukemia (AML) cells and potently induced FLT3-ITD degradation through the ubiquitin-proteasome system. Notably, oral administration of A20 resulted in complete tumor regression on subcutaneous AML xenograft models. Furthermore, on systemic AML xenograft models, A20 could completely eliminate the CD45+CD33+ human leukemic cells in murine and significantly prolonged the survival time of mice. Most importantly, A20 exerted significantly improved antiproliferative activity against drug-resistant AML cells compared to existing FLT3 inhibitors. These findings suggested that A20 could serve as a promising drug candidate for relapsed or refractory AML.

Aerosol-assisted synthesis of mesoporous Cu/ZnO-ZrO2 catalyst with highly selective photothermal CO2 reduction to methanol.

This study uses a facile aerosol-assisted method to synthesize mesoporous Cu/ZnO-ZrO2 catalysts, with superior thermal and photothermal performance for CO2 reduction to methanol. The process is based on forming an aerosol from Zn and Zr precursors and a surfactant solution. Then, fast drying of the droplets was used to obtain the ZnO-ZrO2 support with uniform nanoparticles and 6 nm calibrated mesopores. After impregnation with Cu species, the Cu/ZnO-ZrO2 catalyst exhibited high activity for the targeted reaction, as shown by the high TOFCu values and superior methanol yields and selectivity. Extensive characterization, such as BET, TEM, and photocurrents, confirms the abundant mesopores and relatively high surface area of the ZnO-ZrO2 support synthesized by the aerosol-assisted surfactant method, thus promoting Cu dispersion as well as enhancing the localized surface plasmon resonance (LPSR) effect to generate efficient currents and change the chemical state of Cu by in situ oxidation and reduction to promote a hydrogen overflow effect under visible light irradiation. Therefore, the simple and scalable aerosol-assisted process presented in this study provides new insight into the fabrication of composite mesoporous oxide as a promising photothermal catalyst.

Flattening-Net: Deep Regular 2D Representation for 3D Point Cloud Analysis.

Point clouds are characterized by irregularity and unstructuredness, which pose challenges in efficient data exploitation and discriminative feature extraction. In this paper, we present an unsupervised deep neural architecture called Flattening-Net to represent irregular 3D point clouds of arbitrary geometry and topology as a completely regular 2D point geometry image (PGI) structure, in which coordinates of spatial points are captured in colors of image pixels. Intuitively, Flattening-Net implicitly approximates a locally smooth 3D-to-2D surface flattening process while effectively preserving neighborhood consistency. As a generic representation modality, PGI inherently encodes the intrinsic property of the underlying manifold structure and facilitates surface-style point feature aggregation. To demonstrate its potential, we construct a unified learning framework directly operating on PGIs to achieve diverse types of high-level and low-level downstream applications driven by specific task networks, including classification, segmentation, reconstruction, and upsampling. Extensive experiments demonstrate that our methods perform favorably against the current state-of-the-art competitors.

A mini review on recent progress of steam reforming of ethanol.

H2 is one of the promising renewable energy sources, but its production and transportation remain challenging. Distributed H2 production using liquid H2 carriers is one of the ideal ways of H2 utilization. Among common H2 carriers, ethanol is promising as it has high H2 content and can be derived from renewable bio-energy sources such as sucrose, starch compounds, and cellulosic biomass. To generate H2 from ethanol, steam reforming of ethanol (SRE) is the most common way, while appropriate catalysts, usually supported metal catalysts, are indispensable. However, the SRE process is quite complicated and always accompanied by various undesirable by-products, causing low H2 yield. Moreover, the catalysts for SRE are easy to deactivate due to sintering and carbon deposition under high reaction temperatures. In recent years, lots of efforts have been made to reveal SRE mechanisms and synthesize catalysts with high H2 yield and excellent stability. Both active metals and supports play an important role in the reaction. This mini-review summarizes the recent progress of SRE catalysts from the view of the impacts of active metals and supports and draws an outlook for future research directions.

A brief review: the application of long afterglow luminescent materials in environmental remediation.

Long afterglow luminescent (LAL) materials can release their stored light after turning off the light irradiating on them. Because of this unique characteristic, the coupling of LAL materials and conventional semiconductors is an environmental-friendly method for supporting photocatalytic activity for environmental remediation. Currently, the exploration of "afterglow-catalysis" materials for the fabrication of around-the-clock photocatalytic systems is still in its infancy. Accordingly, herein, we summarize the application of LAL materials in photocatalytic environmental remediation and energy crisis alleviation to stimulate further motivation for the development of novel LAL materials. By discussing the works in the last five years on novel LAL materials, we anticipate the development of new materials, i.e., "afterglow-catalysis" composites, to realize waste-to-energy, even achieving industrialization.

Interactive Effects of Nitrogen and Potassium on Grain Yield and Quality of Waxy Maize.

Reasonable fertilization of nitrogen (N) and potassium (K) had significant effects on maize growth. In this experiment, two N levels (N180 and N225 kg ha-1) and four K treatments (K0, K75, K150 and K75 + 75 kg ha-1) were set to study the effects of combined application of N and K on the grain yield and quality of waxy maize. The results showed that grain yield increased with increasing K under the same N level, and top-dressing K further increased the grain yield. K application increased starch content significantly at N180 and decreased significantly at N225, while the protein content increased significantly at the two N levels. The grain starch content with the K75 + 75 treatment increased by 5.8% and 9.0% compared with K150 at the two N levels, and the protein content decreased by 2.9% and 4.7%. Application of K increased the retrogradation enthalpy (ΔHret) and retrogradation percentage (%R) at N180. At N225, the ΔHret and %R of K75 and K150 decreased, while those of K75 + 75 increased. The ΔHret and %R under K75 + 75 at N180 were lower than N225. Under these experiment conditions, 75 kg ha-1 K2O at sowing date and top-dressed 75 kg ha-1 K2O at jointing stage (V6) under the conditions of appropriate N reduction could not only effectively improve the pasting and thermal properties of waxy maize flour, but also stabilized the grain yield.

Effective Transport Tunnels Achieved by 1,2,4,5-Tetrazine-Induced Intermolecular C-H...N Interaction and Anion Radicals for Stable ReRAM Performance.

The D-A structured small-molecule-based resistive random-access memory (ReRAM) device has been well-researched in the last decade, and the switching mechanism was mainly induced by the intramolecular/intermolecular charge transfer processes from the donors to the acceptors. However, in the previous work, some small molecules with pristine electron acceptors in the backbone could still show the typical memory behaviors, of which the switching mechanism is still ambiguous. In this work, two 1,2,4,5-tetrazine based n-type small-molecular isomers, 2-DPTZ and 4-DPTZ, with the same electron acceptor, 1,2,4,5-tetrazine and pyridine, are chosen to investigate the isomeric effects on molecular packing, switching mechanism, and memory performance. Because of the abundant nitrogen atoms with a localized lone pair of electrons in the sp2 orbital, 2-DPTZ and 4-DPTZ compounds could self-assemble into a long-range ordered molecular packing through intermolecular C-H...N interactions, affording effective transporting tunnels for charge-carrier transport. As expected, the sandwich-structured ITO/2-DPTZ or 4-DPTZ/Al memory devices both showed binary memory characteristics, with 2-DPTZ based memory devices showing the write once read many times (WORM) memory behavior and 4-DPTZ based memory devices having the negative differential resistance (NDR) memory performance. These distinct ReRAM properties arose from the different morphologies of 2-DPTZ and 4-DPTZ films that were induced by the different packing styles between the adjacent molecules, as confirmed by X-ray diffraction (XRD) and tapping-mode atomic force microscopy (AFM) height images. Most importantly, the switching mechanism was thought to be attributed to the injected electrons that reduced the neutral molecules of 2-DPTZ and 4-DPTZ to their corresponding anion radicals. Thus, this present work helps us better understand the conducting mechanism of small molecules with pristine electron acceptors in the backbone and provides a supplementary guideline for designing multilevel small molecules to match the structure-stacking-property relationship.

A low-cost commercial Cu(II)-EDTA complex for electrocatalytic water oxidation in neutral aqueous solution.

Herein, we choose a commercial Cu complex [Cu(EDTA)(H2O)] (EDTA = ethylene diamine tetraacetic acid) as a molecular catalyst for water oxidation to avoid complex synthesis and lower catalyst cost. [Cu(EDTA)(H2O)] could catalyze the water oxidation reaction efficiently under neutral conditions with an overpotential of 684 mV, a kcat of 8.03 s-1 and good stability in the long-term electrolysis. Our finding is of great significance for the development of stable, rapid, and easily accessible catalysts for water oxidation.

A Novel Peptide from Polypedates megacephalus Promotes Wound Healing in Mice.

Amphibian skin contains wound-healing peptides, antimicrobial peptides, and insulin-releasing peptides, which give their skin a strong regeneration ability to adapt to a complex and harsh living environment. In the current research, a novel wound-healing promoting peptide, PM-7, was identified from the skin secretions of Polypedates megacephalus, which has an amino acid sequence of FLNWRRILFLKVVR and shares no structural similarity with any peptides described before. It displays the activity of promoting wound healing in mice. Moreover, PM-7 exhibits the function of enhancing proliferation and migration in HUVEC and HSF cells by affecting the MAPK signaling pathway. Considering its favorable traits as a novel peptide that significantly promotes wound healing, PM-7 can be a potential candidate in the development of novel wound-repairing drugs.

A minireview on the synthesis of single atom catalysts.

Single atom catalysis is a prosperous and rapidly growing research field, owing to the remarkable advantages of single atom catalysts (SACs), such as maximized atom utilization efficiency, tailorable catalytic activities as well as supremely high catalytic selectivity. Synthesis approaches play crucial roles in determining the properties and performance of SACs. Over the past few years, versatile methods have been adopted to synthesize SACs. Herein, we give a thorough and up-to-date review on the progress of approaches for the synthesis of SACs, outline the general principles and list the advantages and disadvantages of each synthesis approach, with the aim to give the readers a clear picture and inspire more studies to exploit novel approaches to synthesize SACs effectively.

A minireview on catalysts for photocatalytic N2 fixation to synthesize ammonia.

Ammonia (NH3) is an important feedstock in chemical industry. Nowadays NH3 is mainly produced via the industrialized Haber-Bosch process, which requires substantial energy input, since it operates at high temperatures (400-650 °C) and high pressures (20-40 Mpa). From the energy conservation point of view, it is of great significance to explore an alternative avenue to synthesize NH3, which is in line with the concept of sustainable development. Very recently, photocatalytic N2 fixation (PNF) has been discovered as a safe and green approach to synthesize NH3, as it utilizes the inexhaustible solar energy and the abundant N2 in nature to synthesize NH3 under mild conditions. A highly efficient catalyst is the core of PNF. Up to now, extensive studies have been conducted to design efficient catalysts for PNF. Summarizing the catalysts reported for PNF and unraveling their reaction mechanisms could provide guidance for the design of better catalysts. In this review, we will illustrate the development of catalysts for PNF, including semiconductors, plasmonic metal-based catalysts, iron-based catalysts, ruthenium-based catalysts and several other catalysts, point out the remaining challenges and outline the future opportunities, with the aim to contribute to the development of PNF.

Effect of preparation methods of CeO2 on the properties and performance of Ni/CeO2 in CO2 reforming of CH4.

CO2 reforming of CH4 (CRM) is not only beneficial to environmental protection, but also valuable for industrial application. Different CeO2 supports were prepared to investigate the matching between Ni and CeO2 over Ni/CeO2 and its effect on CRM. The physicochemical properties of Ni/CeO2-C (commercial CeO2), Ni/CeO2-H (hydrothermal method) as well as Ni/CeO2-P (precipitation method) were characterized by XRD, N2 adsorption at - 196 °C, TEM, SEM-EDS, H2-TPR, NH3-TPD and XPS. Ni0 with good dispersion and CeO2 with more oxygen vacancies were obtained on Ni/CeO2-H, proving the influence on Ni/CeO2 catalysts caused by the preparation methods of CeO2. The initial conversion of both CO2 and CH4 of Ni/CeO2-H was more than five times that of Ni/CeO2-P and Ni/CeO2-C. The better matching between Ni and CeO2 on Ni/CeO2-H was the reason for its best catalytic performance in comparison with the Ni/CeO2-C and Ni/CeO2-P samples.

Epigenetic Activation of lncRNA MIR155HG Mediated by Promoter Hypomethylation and SP1 is Correlated with Immune Infiltration in Glioma.

Purpose: The lncRNA MIR155 host gene (MIR155HG) plays a role in the progression of several malignant cancers. However, the specific mechanisms of MIR155HG in glioma progression have not been clearly established. The purpose of this study was to investigate the function of MIR155HG in glioma at the transcriptome level and relationship with immune infiltration. Patients and Methods: Totally, 697 RNA-seq and 594 DNA methylation data were retrieved from The Cancer Genome Atlas (TCGA) dataset while 325 RNA-seq data were retrieved from the Chinese Glioma Genome Atlas (CGGA) dataset. The DNA methylation levels of MIR155HG CpG islands were assessed through bisulfite amplicon sequencing (BSAS). The regulatory mechanism of SP1 on MIR155HG was examined by chromatin immunoprecipitation (ChIP) and luciferase reporter assays. R language was used as the main tool for statistical analysis and graphical work. Results: MIR155HG was predominantly expressed in the isocitrate dehydrogenase (IDH) wild-type as well as mesenchymal subtype gliomas. Promoter methylation levels of MIR155HG in glioblastoma (GBM) were remarkably decreased compared with those in lower-grade glioma (LGG). In addition, there were negative correlations between promoter methylation levels and MIR155HG expressions but positive correlations with patients' overall survival. In vitro studies further revealed that MIR155HG expression was regulated by DNA promoter methylation and transcription factor (SP1) binding to the promoter. Moreover, there was a close association between MIR155HG expression and immune as well as stromal cell infiltrations, inflammatory activities, and immune checkpoints. Clinically, univariate and multivariate Cox analyses revealed that MIR155HG is an independent prognostic marker for glioma patients. Conclusion: Our results established that MIR155HG is a potential biomarker for prognosis and an immunotherapeutic target in glioma.