Spatiotemporal evolution of AML immune microenvironment remodeling and RNF149-driven drug resistance through single-cell multidimensional analysis.

BACKGROUND: The composition of the bone marrow immune microenvironment in patients with acute myeloid leukaemia (AML) was analysed by single-cell sequencing and the evolutionary role of different subpopulations of T cells in the development of AML and in driving drug resistance was explored in conjunction with E3 ubiquitin ligase-related genes. METHODS: To elucidate the mechanisms underlying AML-NR and Ara-C resistance, we analyzed the bone marrow immune microenvironment of AML patients by integrating multiple single-cell RNA sequencing datasets. When compared to the AML disease remission (AML-CR) cohort, AML-NR displayed distinct cellular interactions and alterations in the ratios of CD4+T, Treg, and CD8+T cell populations. RESULTS: Our findings indicate that the E3 ubiquitin ligase RNF149 accelerates AML progression, modifies the AML immune milieu, triggers CD8+T cell dysfunction, and influences the transformation of CD8+ Navie.T cells to CD8+TExh, culminating in diminished AML responsiveness to chemotherapeutic agents. Experiments both in vivo and in vitro revealed RNF149's role in enhancing AML drug-resistant cell line proliferation and in apoptotic inhibition, fostering resistance to Ara-C. CONCLUSION: In essence, the immune microenvironments of AML-CR and AML-NR diverge considerably, spotlighting RNF149's tumorigenic function in AML and cementing its status as a potential prognostic indicator and innovative therapeutic avenue for countering AML resistance.

Abnormal expression of galectin-1, -3 leading to unexplained infertility by decreasing endometrial receptivity: a retrospective analysis.

OBJECTIVE: To explore the relationship between galectin-1, -3 and unexplained infertility and the effect on endometrial receptivity. METHODS: The clinical data of 100 female patients at childbearing age coming to Xingtai People's Hospital from February 2019 to February 2021 were collected retrospectively. Based on normal pregnancy or not, 50 infertility patients were placed into an infertility group, and 50 patients with normal pregnancy history were placed into a normal group. The mRNA and protein levels of galectin-1, -3, endometrial wave-like activity, endometrial thickness, uterine artery pulsatility index (PI), resistance index (RI), end diastolic velocity (EDV) and peak systolic velocity (PSV) ratio (S/D = PSV/EDV) were compared between the two groups of patients. RESULTS: The mRNA and protein levels of galectin-1, -3 in the infertile group were lower than those in the normal group (P<0.05). In addition, the endometrial wave-like activity in the infertile group was more than that in the normal group (P<0.05). The endometrial thickness was less, while PI, RI and S/D were higher in the infertile group than those in the normal group (P<0.05). CONCLUSION: The low mRNA and protein expressions of galectin-1, -3 in unexplained infertility can affect endometrial receptivity, which may be closely related to unexplained infertility.

Unlocking the potential of polymeric desalination membranes by understanding molecular-level interactions and transport mechanisms.

Polyamide reverse osmosis (PA-RO) membranes achieve remarkably high water permeability and salt rejection, making them a key technology for addressing water shortages through processes including seawater desalination and wastewater reuse. However, current state-of-the-art membranes suffer from challenges related to inadequate selectivity, fouling, and a poor ability of existing models to predict performance. In this Perspective, we assert that a molecular understanding of the mechanisms that govern selectivity and transport of PA-RO and other polymer membranes is crucial to both guide future membrane development efforts and improve the predictive capability of transport models. We summarize the current understanding of ion, water, and polymer interactions in PA-RO membranes, drawing insights from nanofiltration and ion exchange membranes. Building on this knowledge, we explore how these interactions impact the transport properties of membranes, highlighting assumptions of transport models that warrant further investigation to improve predictive capabilities and elucidate underlying transport mechanisms. We then underscore recent advances in in situ characterization techniques that allow for direct measurements of previously difficult-to-obtain information on hydrated polymer membrane properties, hydrated ion properties, and ion-water-membrane interactions as well as powerful computational and electrochemical methods that facilitate systematic studies of transport phenomena.

Advanced nanoparticles that can target therapy and reverse drug resistance may be the dawn of leukemia treatment: A bibliometrics study.

With the development of nanomedicine, more and more nanoparticles are used in the diagnosis and treatment of leukemia. This study aimed to identify author, country, institutional, and journal collaborations and their impacts, assess the knowledge base, identify existing trends, and uncover emerging topics related to leukemia research. 1825 Articles and reviews were obtained from the WoSCC and analyzed by Citespace and Vosviewer. INTERNATIONAL JOURNAL OF NANOMEDICINE is the journal with the highest output. The contribution of FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY is also noteworthy. The three main aspects of research in Nanoparticles-leukemia-related fields included nanoparticles for the diagnosis and treatment of leukemia, related to the type and treatment of leukemia, the specific molecular mechanism, and existing problems of the application of nanoparticles in leukemia. In the future, synthesize nano-drugs that have targeted therapy and chemotherapy resistance according to the mechanism, which may be the dawn of the solution to leukemia. This study offers a comprehensive overview of the Nanoparticles-leukemia-related field using bibliometrics and visual methods for the first time, providing a valuable reference for researchers interested in Nanoparticles-leukemia.

Enabling Magnesium Anodes by Tuning the Electrode/Electrolyte Interfacial Structure.

A new deposition mechanism is presented in this study to achieve highly reversible plating and stripping of magnesium (Mg) anodes for Mg-ion batteries. It is known that the reduction of electrolyte anions such as bis(trifluoromethanesulfonyl)imide (TFSI-) causes Mg surface passivation, resulting in poor electrochemical performance for Mg-ion batteries. We reveal that the addition of sodium cations (Na+) in Mg-ion electrolytes can fundamentally alter the interfacial chemistry and structure at the Mg anode surface. The molecular dynamics simulation suggests that Na+ cations contribute to a significant population in the interfacial double layer so that TFSI- anions are excluded from the immediate interface adjacent to the Mg anode. As a result, the TFSI- decomposition is largely suppressed so does the formation of passivation layers at the Mg surface. This mechanism is supported by our electrochemical, microscopic, and spectroscopic analyses. The resultant Mg deposition demonstrates smooth surface morphology and lowered overpotential compared to the pure Mg(TFSI)2 electrolyte.

CircNPM1 strengthens Adriamycin resistance in acute myeloid leukemia by mediating the miR-345-5p/FZD5 pathway.

Acute myeloid leukemia (AML) is an aggressive hematological malignancy with poor long-term outcomes. Numerous studies claim that circular RNAs (circRNAs) are important regulators in AML progression. This study intended to explore the role of circNPM1 in AML development and drug chemoresistance. The expression of circNPM1 and miR-345-5p was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cellular activities, including cell growth, apoptosis, cell cycle, migration and invasion, were monitored using colony formation assay, flow cytometry assay and transwell assay, respectively. The relationship between miR-345-5p and circNPM1 or Frizzled-5 (FZD5) was predicted by the bioinformatics tool starBase and validated by dual-luciferase reporter assay or RNA immunoprecipitation (RIP) assay. CircNPM1 was abundantly expressed in serum samples from AML patients and AML cell lines. CircNPM1 silence or miR-345-5p restoration repressed colony formation, cell migration and invasion, contributed to cell apoptosis and cell cycle arrest, and weakened Adriamycin (ADM) resistance of AML cells. MiR-345-5p was a target of circNPM1 and was downregulated in AML serum and cells. MiR-345-5p deficiency reversed the effects of circNPM1 silence. Further, FZD5 was targeted by miR-345-5p, and circNPM1 regulated FZD5 expression by adsorbing miR-345-5p. FZD5 overexpression could block the function of miR-345-5p restoration. CircNPM1 might be a vital regulator for ADM chemoresistance in AML cells, which partly depended on the role of the miR-345-5p/FZD5 axis. Our study presents the view that circNPM1 degradation may be a key strategy in AML resistance therapy.

Integrative Analysis of Gene Expression Through One-Class Logistic Regression Machine Learning Identifies Stemness Features in Multiple Myeloma.

Tumor progression includes the obtainment of progenitor and stem cell-like features and the gradual loss of a differentiated phenotype. Stemness was defined as the potential for differentiation and self-renewal from the cell of origin. Previous studies have confirmed the effective application of stemness in a number of malignancies. However, the mechanisms underlying the growth and maintenance of multiple myeloma (MM) stem cells remain unclear. We calculated the stemness index for samples of MM by utilizing a novel one-class logistic regression (OCLR) machine learning algorithm and found that mRNA expression-based stemness index (mRNAsi) was an independent prognostic factor of MM. Based on the same cutoff value, mRNAsi could stratify MM patients into low and high groups with different outcomes. We identified 127 stemness-related signatures using weighted gene co-expression network analysis (WGCNA) and differential expression analysis. Functional annotation and pathway enrichment analysis indicated that these genes were mainly involved in the cell cycle, cell differentiation, and DNA replication and repair. Using the molecular complex detection (MCODE) algorithm, we identified 34 pivotal signatures. Meanwhile, we conducted unsupervised clustering and classified the MM cohorts into three MM stemness (MMS) clusters with distinct prognoses. Samples in MMS-cluster3 possessed the highest stemness fractions and the worst prognosis. Additionally, we applied the ESTIMATE algorithm to infer differential immune infiltration among the three MMS clusters. The immune core and stromal score were significantly lower in MMS-cluster3 than in the other clusters, supporting the negative relation between stemness and anticancer immunity. Finally, we proposed a prognostic nomogram that allows for individualized assessment of the 3- and 5-year overall survival (OS) probabilities among patients with MM. Our study comprehensively assessed the MM stemness index based on large cohorts and built a 34-gene based classifier for predicting prognosis and potential strategies for stemness treatment.

Strategies to Enable Reversible Magnesium Electrochemistry: From Electrolytes to Artificial Solid-Electrolyte Interphases.

The first prototype of a rechargeable magnesium (Mg) battery demonstrated two decades ago sparked tremendous interest in the electrochemical community due to their potential low cost, high volumetric energy density. However, the development of rechargeable Mg batteries has been hampered by the incompatibility between the Mg-metal anode and conventional carbonate electrolytes. Research has focused on electrolytes that are thermodynamically stable against reduction at the expense of low oxidation potential at the cathode side. Alternatively, the use of an artificial solid-electrolyte interphase (SEI) via surface coating presents promising results to address the Mg/electrolyte incompatibility and significantly broaden the selection of electrolytes. This minireview discusses the limitations of electrolyte development and strategies for the design of artificial interphases in magnesium-ion batteries. Future perspectives in the development of artificial interphases for rechargeable magnesium batteries are also discussed.

High Current Cycling in a Superconcentrated Ionic Liquid Electrolyte to Promote Uniform Li Morphology and a Uniform LiF-Rich Solid Electrolyte Interphase.

High-energy-density systems with fast charging rates and suppressed dendrite growth are critical for the implementation of efficient and safe next-generation advanced battery technologies such as those based on Li metal. However, there are few studies that investigate reliable cycling of Li metal electrodes under high-rate conditions. Here, by employing a superconcentrated ionic liquid (IL) electrolyte, we highlight the effect of Li salt concentration and applied current density on the resulting Li deposit morphology and solid electrolyte interphase (SEI) characteristics, demonstrating exceptional deposition/dissolution rates and efficiency in these systems. Operation at higher current densities enhanced the cycling efficiency, e.g., from 64 ± 3% at 1 mA cm-2 up to 96 ± 1% at 20 mA cm-2 (overpotential <±0.2 V), while resulting in lower electrode resistance and dendrite-free Li morphology. A maximum current density of 50 mA cm-2 resulted in 88 ± 3% cycling efficiency, displaying tolerance for high overpotentials at the Ni working electrode (0.5 V). X-ray photoelectron microscopy (XPS), time-of-flight secondary-ion mass spectroscopy (ToF-SIMS), and scanning electron microscopy (SEM) surface measurements revealed that the formation of a stable SEI, rich in LiF and deficient in organic carbon species, coupled with nondendritic and compact Li morphologies enabled enhanced cycling efficiency at higher currents. Reduced dendrite formation at high current is further highlighted by the use of a highly porous separator in coin cell cycling (1 mAh cm-2 at 50 °C), sustaining 500 cycles at 10 mA cm-2.

Surface SiO2 Thickness Controls Uniform-to-Localized Transition in Lithiation of Silicon Anodes for Lithium-Ion Batteries.

Silicon is a promising anode material for lithium-ion batteries because of its high capacity, but its widespread adoption has been hampered by a low cycle life arising from mechanical failure and the absence of a stable solid-electrolyte interphase (SEI). Understanding SEI formation and its impact on cycle life is made more complex by the oxidation of silicon materials in air or during synthesis, which leads to SiOx coatings of varying thicknesses that form the true surface of the electrode. In this paper, the lithiation of SiO2-coated Si is studied in a controlled manner using SiO2 coatings of different thicknesses grown on Si wafers via thermal oxidation. SiO2 thickness has a profound effect on lithiation: below 2 nm, SEI formation followed by uniform lithiation occurs at positive voltages versus Li/Li+. Si lithiation is reversible, and SiO2 lithiation is largely irreversible. Above 2 nm SiO2, voltammetric currents decrease exponentially with SiO2 thickness. For 2-3 nm SiO2, SEI formation above 0.1 V is suppressed, but a hold at low or negative voltages can initiate charge transfer whereupon SEI formation and uniform lithiation occur. Cycling of Si anodes with an SiO2 coating thinner than 3 nm occurs at high Coulombic efficiency (CE). If an SiO2 coating is thicker than 3-4 nm, the behavior is totally different: lithiation at positive voltages is strongly inhibited, and lithiation occurs at poor CE and is highly localized at pinholes which grow over time. As they grow, lithiation becomes more facile and the CE increases. Pinhole growth is proposed to occur via rapid transport of Li along the SiO2/Si interface radially outward from an existing pinhole, followed by the lithiation of SiO2 from the interface outward.

Nonpassivated Silicon Anode Surface.

A stable solid electrolyte interphase (SEI) has been proven to be a key enabler to most advanced battery chemistries, where the reactivity between the electrolyte and the anode operating beyond the electrolyte stability limits must be kinetically suppressed by such SEIs. The graphite anode used in state-of-the-art Li-ion batteries presents the most representative SEI example. Because of similar operation potentials between graphite and silicon (Si), a similar passivation mechanism has been thought to apply on the Si anode when using the same carbonate-based electrolytes. In this work, we found that the chemical formation process of a proto-SEI on Si is closely entangled with incessant SEI decomposition, detachment, and reparation, which lead to continuous lithium consumption. Using a special galvanostatic protocol designed to observe the SEI formation prior to Si lithiation, we were able to deconvolute the electrochemical formation of such dynamic SEI from the morphology and mechanical complexities of Si and showed that a pristine Si anode could not be fully passivated in carbonate-based electrolytes.

Spatially Resolving Lithiation in Silicon-Graphite Composite Electrodes via in Situ High-Energy X-ray Diffraction Computed Tomography.

Optimizing the chemical and morphological parameters of lithium-ion (Li-ion) electrodes is extremely challenging, due in part to the absence of techniques to construct spatial and temporal descriptions of chemical and morphological heterogeneities. We present the first demonstration of combined high-speed X-ray diffraction (XRD) and XRD computed tomography (XRD-CT) to probe, in 3D, crystallographic heterogeneities within Li-ion electrodes with a spatial resolution of 1 µm. The local charge-transfer mechanism within and between individual particles was investigated in a silicon(Si)-graphite composite electrode. High-speed XRD revealed charge balancing kinetics between the graphite and Si during the minutes following the transition from operation to open circuit. Subparticle lithiation heterogeneities in both Si and graphite were observed using XRD-CT, where the core and shell structures were segmented, and their respective diffraction patterns were characterized.

Interfacially Induced Cascading Failure in Graphite-Silicon Composite Anodes.

Silicon (Si) has been well recognized as a promising candidate to replace graphite because of its earth abundance and high-capacity storage, but its large volume changes upon lithiation/delithiation and the consequential material fracturing, loss of electrical contact, and over-consumption of the electrolyte prevent its full application. As a countermeasure for rapid capacity decay, a composite electrode of graphite and Si has been adopted by accommodating Si nanoparticles in a graphite matrix. Such an approach, which involves two materials that interact electrochemically with lithium in the electrode, necessitates an analytical methodology to determine the individual electrochemical behavior of each active material. In this work, a methodology comprising differential plots and integral calculus is established to analyze the complicated interplay among the two active batteries and investigate the failure mechanism underlying capacity fade in the blend electrode. To address performance deficiencies identified by this methodology, an aluminum alkoxide (alucone) surface-modification strategy is demonstrated to stabilize the structure and electrochemical performance of the graphite-Si composite electrode. The integrated approach established in this work is of great importance to the design and diagnostics of a multi-component composite electrode, which is expected to be high interest to other next-generation battery system.

Operando X-ray photoelectron spectroscopy of solid electrolyte interphase formation and evolution in Li2S-P2S5 solid-state electrolytes.

Solid-state electrolytes such as Li2S-P2S5 compounds are promising materials that could enable Li metal anodes. However, many solid-state electrolytes are unstable against metallic lithium, and little is known about the chemical evolution of these interfaces during cycling, hindering the rational design of these materials. In this work, operando X-ray photoelectron spectroscopy and real-time in situ Auger electron spectroscopy mapping are developed to probe the formation and evolution of the Li/Li2S-P2S5 solid-electrolyte interphase during electrochemical cycling, and to measure individual overpotentials associated with specific interphase constituents. Results for the Li/Li2S-P2S5 system reveal that electrochemically driving Li+ to the surface leads to phase decomposition into Li2S and Li3P. Additionally, oxygen contamination within the Li2S-P2S5 leads initially to Li3PO4 phase segregation, and subsequently to Li2O formation. The spatially non-uniform distribution of these phases, coupled with differences in their ionic conductivities, have important implications for the overall properties and performance of the solid-electrolyte interphase.

An artificial interphase enables reversible magnesium chemistry in carbonate electrolytes.

Magnesium-based batteries possess potential advantages over their lithium counterparts. However, reversible Mg chemistry requires a thermodynamically stable electrolyte at low potential, which is usually achieved with corrosive components and at the expense of stability against oxidation. In lithium-ion batteries the conflict between the cathodic and anodic stabilities of the electrolytes is resolved by forming an anode interphase that shields the electrolyte from being reduced. This strategy cannot be applied to Mg batteries because divalent Mg2+ cannot penetrate such interphases. Here, we engineer an artificial Mg2+-conductive interphase on the Mg anode surface, which successfully decouples the anodic and cathodic requirements for electrolytes and demonstrate highly reversible Mg chemistry in oxidation-resistant electrolytes. The artificial interphase enables the reversible cycling of a Mg/V2O5 full-cell in the water-containing, carbonate-based electrolyte. This approach provides a new avenue not only for Mg but also for other multivalent-cation batteries facing the same problems, taking a step towards their use in energy-storage applications.

Systematic Investigation of the Alucone-Coating Enhancement on Silicon Anodes.

Polyvinylidene fluoride (PVDF) is the most popular binder in commercial lithium-ion batteries but is incompatible with a silicon (Si) anode because it fails to maintain the mechanical integrity of the Si electrode upon cycling. Herein, an alucone coating synthesized by molecular layer deposition has been applied on the laminated electrode fabricated with PVDF to systematically study the sole impact of the surface modification on the electrochemical and mechanical properties of the Si electrode, without the interference of other functional polymer binders. The enhanced mechanical properties of the coated electrodes, confirmed by mechanical characterization, can help accommodate the repeated volume fluctuations, preserve the electrode structure during electrochemical reactions, and thereby, leading to a remarkable improvement of the electrochemical performance. Owing to the alucone coating, the Si electrodes achieve highly reversible cycling performance with a specific capacity of 1490 mA h g-1 (0.90 mA h cm-2) as compared to 550 mA h g-1 (0.19 mA h cm-2) observed in the uncoated Si electrode. This research elucidates the important role of surface modification in stabilizing the cycling performance and enabling a high level of material utilization at high mass loading. It also provides insights for the future development of Si anodes.

In Situ Engineering of the Electrode-Electrolyte Interface for Stabilized Overlithiated Cathodes.

The first-ever demonstration of stabilized Si/lithium-manganese-rich full cells, capable of retaining >90% energy over early cycling and >90% capacity over more than 750 cycles at the 1C rate (100% depth-of-discharge), is made through the utilization of a modified ionic-liquid electrolyte capable of forming a favorable cathode-electrolyte interface.

Improved Electrochemical Performance of Carbon-Coated LiFeBO3 Nanoparticles for Lithium-Ion Batteries.

Carbon-coated LiFeBO3 nanoparticles have been successfully prepared by surfactant-assisted ball milling and a size selection process based on centrifugal separation. Monodispersed LiFeBO3 nanoparticles with dimensions of 10-20 nm are observed by transmission electron microscope. The introduced surfactant acts as the dispersant as well as the carbon source for LiFeBO3 nanoparticles. Greatly improved discharge capacities of 190.4 mA h g(-1) at 0.1 C and 106.6 mA h g(-1) at 1 C rate have been achieved in the LiFeBO3 nanoparticles when cycling the cells between 1.0 V and 4.8 V. Meanwhile, the as-prepared micro-size LiFeBO3 electrodes show lower discharge capacities of 142 mA h g(-1) and 93.3 mA h g(-1) at 0.1 C and 1 C rates. The post-treated LiFeBO3 nanostructure has drastically enhanced the electrochemical performance due to the short diffusion length and ameliorated electrical contract between LiFeBO3 nano particles.

Facile Synthesis of Lithium Sulfide Nanocrystals for Use in Advanced Rechargeable Batteries.

This work reports a new method of synthesizing anhydrous lithium sulfide (Li2S) nanocrystals and demonstrates their potential as cathode materials for advanced rechargeable batteries. Li2S is synthesized by reacting hydrogen sulfide (H2S) with lithium naphthalenide (Li-NAP), a thermodynamically spontaneous reaction that proceeds to completion rapidly at ambient temperature and pressure. The process completely removes H2S, a major industrial waste, while cogenerating 1,4-dihydronaphthalene, itself a value-added chemical that can be used as liquid fuel. The phase purity, morphology, and homogeneity of the resulting nanopowders were confirmed by X-ray diffraction and scanning electron microscopy. The synthesized Li2S nanoparticles (100 nm) were assembled into cathodes, and their performance was compared to that of cathodes fabricated using commercial Li2S micropowders (1-5 µm). Electrochemical analyses demonstrated that the synthesized Li2S were superior in terms of (dis)charge capacity, cycling stability, output voltage, and voltage efficiency.

Structure and Reactivity of Alucone-Coated Films on Si and Li(x)Si(y) Surfaces.

Coating silicon particles with a suitable thin film has appeared as a possible solution to accommodate the swelling of silicon upon lithiation and its posterior cracking and pulverization during cycling of Li-ion batteries. In particular, aluminum alkoxide (alucone) films have been recently deposited over Si anodes, and the lithiation and electrochemical behavior of the system have been characterized. However, some questions remain regarding the lithium molecular migration mechanisms through the film and the electronic properties of the alucone film. Here we use density functional theory, ab initio molecular dynamics simulations, and Green's function theory to examine the film formation, lithiation, and reactivity in contact with an electrolyte solution. It is found that the film is composed of Al-O complexes with 3-O or 4-O coordination. During lithiation, Li atoms bind very strongly to the O atoms in the most energetically favorable sites. After the film is irreversibly saturated with Li atoms, it becomes electronically conductive. The ethylene carbonate molecules in liquid phase are found to be reduced at the surface of the Li-saturated alucone film following similar electron transfer mechanisms as found previously for lithiated silicon anodes. The theoretical results are in agreement with those from morphology and electrochemical analyses.