CO2 Hydrogenation to Methanol over Mesoporous SiO2-Coated Cu-Based Catalysts.

Although chemical promotion led to essential improvements in Cu-based catalysts for CO2 hydrogenation to methanol, surpassing structural limitations such as active phase aggregation under reaction conditions remains challenging. In this report, we improved the textural properties of Cu/In2O3/CeO2 and Cu/In2O3/ZrO2 catalysts by coating the nanoparticles with a mesoporous SiO2 shell. This strategy limited particle size up to 3.5 nm, increasing metal dispersion and widening the metal-metal oxide interface region. Chemometric analysis revealed that these structures could maintain high activity and selectivity in a wide range of reaction conditions, with methanol space-time yields up to 4 times higher than those of the uncoated catalysts.

Versatile Method of Engineering the Band Alignment and the Electron Wavefunction Hybridization of Hybrid Quantum Devices.

Hybrid devices that combine superconductors (S) and semiconductors (Sm) have attracted great attention due to the integration of the properties of both materials, which relies on the interface details and the resulting coupling strength and wavefunction hybridization. However, until now, none of the experiments have reported good control of the band alignment of the interface, as well as its tunability to the coupling and hybridization. Here, the interface is modified by inducing specific argon milling while maintaining its high quality, e.g., atomic connection, which results in a large induced superconducting gap and ballistic transport. By comparing with Schrödinger-Poisson calculations, it is proven that this method can vary the band bending/coupling strength and the electronic spatial distribution. In the strong coupling regime, the coexistence and tunability of crossed Andreev reflection and elastic co-tunneling-key ingredients for the Kitaev chain-are confirmed. This method is also generic for other materials and achieves a hard and huge superconducting gap in lead and indium antimonide nanowire (Pb-InSb) devices. Such a versatile method, compatible with the standard fabrication process and accompanied by the well-controlled modification of the interface, will definitely boost the creation of more sophisticated hybrid devices for exploring physics in solid-state systems.

Stemless InSb nanowire networks and nanoflakes grown on InP.

Among the experimental realization of fault-tolerant topological circuits are interconnecting nanowires with minimal disorder. Out-of-plane indium antimonide (InSb) nanowire networks formed by merging are potential candidates. Yet, their growth requires a foreign material stem usually made of InP-InAs. This stem imposes limitations, which include restricting the size of the nanowire network, inducing disorder through grain boundaries and impurity incorporation. Here, we omit the stem allowing for the growth of stemless InSb nanowire networks on an InP substrate. To enable the growth without the stem, we show that a preconditioning step using arsine (AsH3) is required before InSb growth. High-yield of stemless nanowire growth is achieved by patterning the substrate with a selective-area mask with nanohole cavities, containing restricted gold droplets from which nanowires originate. Interestingly, these nanowires are bent, posing challenges for the synthesis of interconnecting nanowire networks due to merging failure. We attribute this bending to the non-homogeneous incorporation of arsenic impurities in the InSb nanowires and the interposed lattice-mismatch. By tuning the growth parameters, we can mitigate the bending, yielding large and single crystalline InSb nanowire networks and nanoflakes. The improved size and crystal quality of these nanostructures broaden the potential of this technique for fabricating advanced quantum devices.

The impact of different FLT3-inhibitors on overall survival of de novo acute myeloid leukemia: A network meta-analysis.

FLT3 inhibitors combined with chemotherapy are the standard of care for newly diagnosed FLT3-mutated acute myeloid leukemia (AML). However, no head-to-head studies have established the superiority of one FLT3 inhibitor over another. We conducted a network meta-analysis (NMA) to evaluate overall survival (OS) among different FLT3 inhibitors. Three relevant randomized controlled trials (RCTs), involving 1.358 patients treated with midostaurin, quizartinib, and sorafenib, were included in our analysis. The hazard ratios (HRs) revealed no significant differences in OS between midostaurin and quizartinib (HR, 1.00; 95 % CI, 0.73-1.36), midostaurin and sorafenib (HR, 0.97; 95 % CI, 0.52-1.84), or quizartinib and sorafenib (HR, 0.97; 95 % CI, 0.51-1.85). This NMA, the first to explore this issue, found no OS differences among the different FLT3 inhibitors. In the absence of direct comparison trials, our findings provide practical insights for clinical decision-making.

Multiple use of preservative-free single dose unit dexamethasone 0.1% eye drops is safe within 24 hours.

BACKGROUND: Unpreserved single-dose unit (SDU) eye drops are commonly used to avoid benzalkonium chloride-related toxicity. Although intended for single use, many patients report off-label repeated use of SDUs over a prolonged period. We investigated whether repeated use of dexamethasone 0.1% SDUs in the same patient increases the bacterial contamination rate. METHODS: We prospectively enrolled patients scheduled for inpatient corneal and glaucoma surgery receiving dexamethasone 0.1% SDU four times per day from the same vial. To assess contamination rates, one drop from the vial was cultured immediately after opening the SDU (t0), 10 hours later after four drop applications (t10) and 24 hours after opening without further drop applications (t24). Conjunctival swabs were taken before and after drop application. Contamination rate was assessed with a standard clinical culturing protocol without introducing a positive control. RESULTS: 110 eyes of 109 patients were evaluated. Drops collected immediately after opening the SDU (t0) were contaminated in 9/110 cultures (8.1%). At t10, 13/110 cultures were contaminated (11.8%; p=0.267) and 11/110 at t24 (10.0%; t24 vs t0; p=1.00). In 5 of 21 cases of contaminated drops at t10 and/or t24, the same isolates were cultured from the initial conjunctival swab and the SDU. In three cases, the same bacterial species was found in consecutive samples. CONCLUSION: The contamination rate of the SDU did not increase after multiple use within 24 hours. Contamination from fingertip flora was more likely than from ocular surface flora. Reuse of dexamethasone 0.1% SDU in the same patient within 24 hours appears to be safe.

Rapid generation of human recombinant monoclonal antibodies from antibody-secreting cells using ferrofluid-based technology.

Monoclonal antibodies (mAbs) are one of the most important classes of biologics with high therapeutic and diagnostic value, but traditional methods for mAbs generation, such as hybridoma screening and phage display, have limitations, including low efficiency and loss of natural chain pairing. To overcome these challenges, novel single B cell antibody technologies have emerged, but they also have limitations such as in vitro differentiation of memory B cells and expensive cell sorters. In this study, we present a rapid and efficient workflow for obtaining human recombinant monoclonal antibodies directly from single antigen-specific antibody secreting cells (ASCs) in the peripheral blood of convalescent COVID-19 patients using ferrofluid technology. This process allows the identification and expression of recombinant antigen-specific mAbs in less than 10 days, using RT-PCR to generate linear Ig heavy and light chain gene expression cassettes, called "minigenes", for rapid expression of recombinant antibodies without cloning procedures. This approach has several advantages. First, it saves time and resources by eliminating the need for in vitro differentiation. It also allows individual antigen-specific ASCs to be screened for effector function prior to recombinant antibody cloning, enabling the selection of mAbs with desired characteristics and functional activity. In addition, the method allows comprehensive analysis of variable region repertoires in combination with functional assays to evaluate the specificity and function of the generated antigen-specific antibodies. Our approach, which rapidly generates recombinant monoclonal antibodies from single antigen-specific ASCs, could help to identify functional antibodies and deepen our understanding of antibody dynamics in the immune response through combined antibody repertoire sequence analysis and functional reactivity testing.

Chitosan-Coated Fosetyl-Al Nanocrystals' Efficacy on Nicotiana tabacum Colonized by Xylella fastidiosa.

Xylella fastidiosa (Xf) is a quarantine plant pathogen capable of colonizing the xylem of a wide range of hosts. Currently, there is no cure able to eliminate the pathogen from a diseased plant, but several integrated strategies have been implemented for containing the spread of Xf. Nanotechnology represents an innovative strategy based on the possibility of maximizing the potential antibacterial activity by increasing the surface-to-volume ratio of nanoscale formulations. Nanoparticles based on chitosan and/or fosetyl-Al have shown different in vitro antibacterial efficacy against Xf subsp. fastidiosa (Xff) and pauca (Xfp). This work demonstrated the uptake of chitosan-coated fosetyl-Al nanocrystals (CH-nanoFos) by roots and their localization in the stems and leaves of Olea europaea plants. Additionally, the antibacterial activity of fosetyl-Al, nano-fosetyl, nano-chitosan, and CH-nanoFos was tested on Nicotiana tabacum cultivar SR1 (Petite Havana) inoculated with Xff, Xfp, or Xf subsp. multiplex (Xfm). The bacterial load was evaluated with qPCR, and the results showed that CH-nanoFos was the only treatment able to reduce the colonization of Xff, Xfm, and Xfp in tobacco plants. Additionally, the area under the disease progress curve, used to assess symptom development in tobacco plants inoculated with Xff, Xfm, and Xfp and treated with CH-nanoFos, showed a reduction in symptom development. Furthermore, the twitching assay and bacterial growth under microfluidic conditions confirmed the antibacterial activity of CH-nanoFos.

Clinical Evaluation of Oral Midazolam Containing Cyclodextrin in Pediatric Magnetic Resonance: A Retrospective Cohort Study.

BACKGROUND: Reducing a child's level of anxiety before magnetic resonance imaging (MRI) procedures allows for better behavioral outcomes. The aim of this retrospective study was to evaluate anxiolytic efficacy of Midazolam/γ-cyclodextrin oral formulation. METHODS: We retrospectively reviewed 100 medical charts of children who, between 1 February and 31 July 2022, underwent MRI under general anesthesia with or without premedication with midazolam/γ-cyclodextrin. Primary outcome was comparison of behavior to facemask positioning, while secondary endpoints were degree of drugs acceptance, anxiolytic effect evaluation, child's behavior on separation, and sevoflurane need. RESULTS: Facemask positioning was accepted by 58% of the midazolam/γ-cyclodextrin group compared to 22% of children in the control group. The rate of acceptance was >90%. At the moment of separation from parent, none of the premedicated children needed to be restrained compared to 18% in the control group. A lower percentage of sevoflurane was needed for eye-closure at induction of anesthesia and for anesthesia maintenance. At emergence from anesthesia, 46% of children in the premedicated group compared to 66% of children in the control group showed transient agitation. CONCLUSIONS: Midazolam/γ-cyclodextrin showed a good profile of acceptance, satisfactory anxiolytic properties, and reduced need for anesthetics when administered to children before MRI under general anesthesia.

[A rare cause of acute abdomen in a young immunocompetent woman]. / Seltene Ursache eines akuten Abdomens bei einer jungen immunkompetenten Frau.

Streptococcus pyogenes is a human pathogenic, gram positive bacterium that primarily leads to pharyngitis or soft tissue infections. Primary peritonitis caused by S. pyogenes infection is rare and there are only a few published cases worldwide. Primary peritonitis due to other pathogens occurs in immunosuppressed conditions such as HIV or other chronic diseases. However, younger, healthy women are more likely to be affected by S. pyogenes peritonitis. At present, the underlying molecular mechanisms can only be speculated on. One possibility is that, similar to the clinical picture of streptococcal toxic shock syndrome (STSS), a specific serotype of the M protein in combination with inhibition of the cell response of neutrophil granulocytes could play a role. In addition to peritonitis, the clinical picture may include other organ manifestations such as acute kidney damage or circulatory dysregulation. In terms of treatment, rapid pathogen-directed empirical antibiotic therapy is the treatment of choice. If there is no indication of secondary peritonitis, diagnostic laparoscopy can be dispensed with in the further diagnostic work-up.

Peaglet: A user-friendly probabilistic Kernel density estimation of intracranial cortical and subcortical stimulation sites.

BACKGROUND: Data on human brain function obtained with direct electrical stimulation (DES) in neurosurgical patients have been recently integrated and combined with modern neuroimaging techniques, allowing a connectome-based approach fed by intraoperative DES data. Within this framework is crucial to develop reliable methods for spatial localization of DES-derived information to be integrated within the neuroimaging workflow. NEW METHOD: To this aim, we applied the Kernel Density Estimation for modelling the distribution of DES sites from different patients into the MNI space. The algorithm has been embedded in a MATLAB-based User Interface, Peaglet. It allows an accurate probabilistic weighted and unweighted estimation of DES sites location both at cortical level, by using shortest path calculation along the brain 3D geometric topology, and subcortical level, by using a volume-based approach. RESULTS: We applied Peaglet to investigate spatial estimation of cortical and subcortical stimulation sites provided by recent brain tumour studies. The resulting NIfTI maps have been anatomically investigated with neuroimaging open-source tools. COMPARISON WITH EXISTING METHODS: Peaglet processes differently cortical and subcortical data following their distinguishing geometrical features, increasing anatomical specificity of DES-related results and their reliability within neuroimaging environments. CONCLUSIONS: Peaglet provides a robust probabilistic estimation of the cortical and subcortical distribution of DES sites going beyond a region of interest approach, respecting cortical and subcortical intrinsic geometrical features. Results can be easily integrated within the neuroimaging workflow to drive connectomic analysis.

Association of Clinical, Tumor, and Treatment Characteristics With Seizure Control in Patients With IDH1/2-Mutant Lower-Grade Glioma.

BACKGROUND AND OBJECTIVES: Patients with IDH1/2-mutant lower-grade glioma have a high frequency of seizures. We aimed to investigate the correlations between seizures and tumor/patient characteristics and the impact of surgery and adjuvant treatments (AT) on seizure control along the disease trajectory. METHODS: We retrospectively included patients with IDH1/2-mutant lower-grade glioma who underwent surgery at the neurosurgery divisions of the University of Turin and Milan and were treated at the Division of Neuro-Oncology of Turin. Inclusion criteria were a diagnosis according to the 2021 WHO Classification and presentation with seizures; exclusion criteria were presence of CDKN2A/B homozygous deletion, intense/ring contrast enhancement on MRI at presentation, and small tissue biopsy. We evaluated seizure freedom for 2 months after surgery, 6 months from starting observation or AT, at recurrence, and for 6 months after treatments of recurrence. RESULTS: We included 150 patients. There were 77 (51%) and 31 (21%) patients with IDH-mutant/1p19q-codeleted grade 2 and 3 oligodendroglioma and 30 (20%) and 12 (8%) with IDH-mutant grade 2 and 3 astrocytoma, respectively. Total resection was accomplished in 68 (45%). Seventy-five patients (50%) received AT while the remaining 75 were observed with MRI. After 6 months after AT, 28 of 29 patients (96.5%) displayed seizure reduction, 5 of 28 (18%) being seizure-free. 66 of 124 patients (53%) had seizures at recurrence. After 6 months after second-line treatments, 60 of 66 patients (91%) had seizure reduction, 11 (17%) being seizure-free. In multivariable analyses, grade 3 histology positively correlated with seizure freedom at 2 months after surgery (OR 3.5, 1.4-8.9, p = 0.008), 6 months after AT (OR 9.0, 1.5-54.9, p = 0.017), and 6 months after treatment of recurrence (OR 4.9, 1.5-16.5, p = 0.009). Adjuvant radiotherapy reduced seizures at recurrence in a univariate analysis (OR 0.14, 0.03-0.7, p = 0.020). Patients with seizure freedom after surgery and AT displayed longer progression-free survival (PFS) (65, 24.5-105, vs 48 months, 32-63.5, p = 0.037). DISCUSSION: This study analyzed seizure control in patients with IDH1/2-mutant lower-grade glioma across multiple time points. Grade 3 correlated with better seizure control throughout the entire disease trajectory, and seizure freedom after surgery and AT correlated with a longer PFS regardless of tumor grade. These results could serve as an external control arm in clinical trials evaluating the efficacy on seizures of antitumor agents in patients with IDH-mutant lower-grade glioma.

Strained Silicon Technology: Non-Destructive High-Lateral-Resolution Characterization Through Tip-Enhanced Raman Spectroscopy.

The semiconductor industry is undergoing a transformative phase, marked by the relentless drive for miniaturization and a constant demand for higher performance and energy efficiency. However, the reduction of metal-oxide-semiconductor field-effect transistor sizes for advanced technology nodes below 10 nm presents several challenges. In response, strained silicon technology has emerged as a key player, exploiting strain induction in the silicon crystal lattice to improve device performance. At the same time, there has been a growing need for characterization techniques that allow in-line monitoring of sample conditions during semiconductor manufacturing, as an alternative to traditional methods such as transmission electron microscopy or high-resolution X-ray diffraction, which have several limitations in terms of measurement time and sample destructiveness. This paper explores the application of advanced spectroscopic characterization techniques, in particular µ-Raman spectroscopy and tip-enhanced Raman spectroscopy (TERS), to meet the evolving needs of the semiconductor industry for quality control and failure analysis, increasingly requiring faster and non-destructive characterization techniques. µ-Raman provides insight into strain values and distributions of strained layers with different thicknesses and germanium concentrations, but its lateral resolution is constrained by the Abbe diffraction limit. TERS, on the other hand, emerges as a powerful non-destructive technique capable of overcoming diffraction limits by exploiting the combination of an atomic force microscope with a Raman spectrometer. This breakthrough makes it possible to estimate the chemical composition and induced strain in the lattice by evaluating the Raman peak position shifts in strained and unstrained silicon layers, providing crucial insights for nanoscale strain control. In particular, this paper focuses on the TERS characterization of Si0.7Ge0.3 epitaxial layers grown on a silicon-on-insulator device, demonstrating the effectiveness of this technique and the high lateral resolution that can be achieved.

Toward the nanoscale chemical and physical probing of milk-derived extracellular vesicles using Raman and tip-enhanced Raman spectroscopy.

Tip-enhanced Raman spectroscopy (TERS) is an advanced technique to perform local chemical analysis of the surface of a sample through the improvement of the sensitivity and the spatial resolution of Raman spectroscopy by plasmonic enhancement of the electromagnetic signal in correspondence with the nanometer-sized tip of an atomic force microscope (AFM). In this work, TERS is demonstrated to represent an innovative and powerful approach for studying extracellular vesicles, in particular bovine milk-derived extracellular vesicles (mEVs), which are nanostructures with considerable potential in drug delivery and therapeutic applications. Raman spectroscopy has been used to analyze mEVs at the micrometric and sub-micrometric scales to obtain a detailed Raman spectrum in order to identify the 'signature' of mEVs in terms of their characteristic molecular vibrations and, therefore, their chemical compositions. With the ability to improve lateral resolution, TERS has been used to study individual mEVs, demonstrating the possibility of investigating a single mEV selected on the surface of the sample and, moreover, analyzing specific locations on the selected mEV with nanometer lateral resolution. TERS potentially allows one to reveal local differences in the composition of mEVs providing new insights into their structure. Also, thanks to the intrinsic properties of TERS to acquire the signal from only the first few nanometers of the surface, chemical investigation of the lipid membrane in correspondence with the various locations of the selected mEV could be performed by analyzing the peaks of the Raman shift in the relevant range of the spectrum (2800-3000 cm-1). Despite being limited to mEVs, this work demonstrates the potential of TERS in the analysis of extracellular vesicles.

M1-derived extracellular vesicles polarize recipient macrophages into M2-like macrophages and alter skeletal muscle homeostasis in a hyper-glucose environment.

BACKGROUND: Macrophages release not only cytokines but also extracellular vesicles (EVs). which are small membrane-derived nanovesicles with virus-like properties transferring cellular material between cells. Until now, the consequences of macrophage plasticity on the release and the composition of EVs have been poorly explored. In this study, we determined the impact of high-glucose (HG) concentrations on macrophage metabolism, and characterized their derived-EV subpopulations. Finally, we determined whether HG-treated macrophage-derived EVs participate in immune responses and in metabolic alterations of skeletal muscle cells. METHODS: THP1-macrophages were treated with 15mM (MG15) or 30mM (MG30) glucose. Then, M1/M2 canonical markers, pro- and anti-inflammatory cytokines, activities of proteins involved in glycolysis or oxidative phosphorylation were evaluated. Macrophage-derived EVs were characterized by TEM, NTA, MRSP, and 1H-Nuclear magnetic resonance spectroscopy for lipid composition. Macrophages or C2C12 muscle cells were used as recipients of MG15 and MG30-derived EVs. The lipid profiles of recipient cells were determined, as well as proteins and mRNA levels of relevant genes for macrophage polarization or muscle metabolism. RESULTS: Untreated macrophages released small and large EVs (sEVs, lEVs) with different lipid distributions. Proportionally to the glucose concentration, glycolysis was induced in macrophages, associated to mitochondrial dysfunction, triacylglycerol and cholesterol accumulation. In addition, MG15 and MG30 macrophages had increased level of CD86 and increase release of pro-inflammatory cytokines. HG also affected macrophage sphingolipid and phospholipid compositions. The differences in the lipid profiles between sEVs and lEVs were abolished and reflected the lipid alterations in MG15 and MG30 macrophages. Interestingly, MG15 and MG30 macrophages EVs induced the expression of CD163, Il-10 and increased the contents of triacylglycerol and cholesterol in recipient macrophages. MG15 lEVs and sEVs induced insulin-induced AKT hyper-phosphorylation and accumulation of triacylglycerol in myotubes, a state observed in pre-diabetes. Conversely, MG30 lEVs and sEVs induced insulin-resistance in myotubes. CONCLUSIONS: As inflammation involves first M1 macrophages, then the activation of M2 macrophages to resolve inflammation, this study demonstrates that the dialog between macrophages through the EV route is an intrinsic part of the inflammatory response. In a hyperglycemic context, EV macrophages could participate in the development of muscle insulin-resistance and chronic inflammation.

Thermal scanning probe and laser lithography for patterning nanowire based quantum devices.

Semiconductor nanowire (NW) quantum devices offer a promising path for the pursuit and investigation of topologically-protected quantum states, and superconducting and spin-based qubits that can be controlled using electric fields. Theoretical investigations into the impact of disorder on the attainment of dependable topological states in semiconducting nanowires with large spin-orbit coupling andg-factor highlight the critical need for improvements in both growth processes and nanofabrication techniques. In this work, we used a hybrid lithography tool for both the high-resolution thermal scanning probe lithography and high-throughput direct laser writing of quantum devices based on thin InSb nanowires with contact spacing of 200 nm. Electrical characterization demonstrates quasi-ballistic transport. The methodology outlined in this study has the potential to reduce the impact of disorder caused by fabrication processes in quantum devices based on 1D semiconductors.

Object-oriented hand dexterity and grasping abilities, from the animal quarters to the neurosurgical OR: a systematic review of the underlying neural correlates in non-human, human primate and recent findings in awake brain surgery.

Introduction: The sensorimotor integrations subserving object-oriented manipulative actions have been extensively investigated in non-human primates via direct approaches, as intracortical micro-stimulation (ICMS), cytoarchitectonic analysis and anatomical tracers. However, the understanding of the mechanisms underlying complex motor behaviors is yet to be fully integrated in brain mapping paradigms and the consistency of these findings with intraoperative data obtained during awake neurosurgical procedures for brain tumor removal is still largely unexplored. Accordingly, there is a paucity of systematic studies reviewing the cross-species analogies in neural activities during object-oriented hand motor tasks in primates and investigating the concordance with intraoperative findings during brain mapping. The current systematic review was designed to summarize the cortical and subcortical neural correlates of object-oriented fine hand actions, as revealed by fMRI and PET studies, in non-human and human primates and how those were translated into neurosurgical studies testing dexterous hand-movements during intraoperative brain mapping. Methods: A systematic literature review was conducted following the PRISMA guidelines. PubMed, EMBASE and Web of Science databases were searched. Original articles were included if they: (1) investigated cortical activation sites on fMRI and/or PET during grasping task; (2) included humans or non-human primates. A second query was designed on the databases above to collect studies reporting motor, hand manipulation and dexterity tasks for intraoperative brain mapping in patients undergoing awake brain surgery for any condition. Due to the heterogeneity in neurosurgical applications, a qualitative synthesis was deemed more appropriate. Results: We provided an updated overview of the current state of the art in translational neuroscience about the extended frontoparietal grasping-praxis network with a specific focus on the comparative functioning in non-human primates, healthy humans and how the latter knowledge has been implemented in the neurosurgical operating room during brain tumor resection. Discussion: The anatomical and functional correlates we reviewed confirmed the evolutionary continuum from monkeys to humans, allowing a cautious but practical adoption of such evidence in intraoperative brain mapping protocols. Integrating the previous results in the surgical practice helps preserve complex motor abilities, prevent long-term disability and poor quality of life and allow the maximal safe resection of intrinsic brain tumors.

Luspatercept in low-risk myelodysplastic syndromes: a paradigm shift in treatment strategies.

INTRODUCTION: In patients with myelodysplastic syndromes (MDS), anemia is prevalent affecting 80%-85% of low-risk (LR-MDS) patients, with 40% eventually requiring red blood cell (RBC) transfusions. Except forlenalidomide, exclusively approved for those with deletion of chromosome 5q,erythropoiesis-stimulating agents (ESAs) are the primary treatment choice for low-risk patients. Those unresponsive to ESAs face limited alternatives, eventually necessitating long-term RBC transfusions, leading to secondary iron overload and adversely affecting quality of life (QoL). AREA COVERED: Luspatercept is a pioneering erythroid maturation agent. It received approval by both the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) for treating adults experiencing transfusion-dependent anemia associated with LR-MDS or ß-thalassemia. Recently, the FDA approved luspatercept as first- line therapy in patients with very low- to intermediate-risk MDS who require RBC transfusions and have not previously received ESAs. This review summarizes the historical impact of luspatercept intreating LR-MDS unresponsive to ESAs and illustrates its potential benefit asfrontline therapy in MDS and its employment in patients with myelofibrosis-induced anemia. EXPERT OPINION: Luspatercept has revolutionized the therapeutic paradigm of LR-MDS, for which there was a limited therapeutic arsenal, especially in the setting of patients who did not respond or fail after ESA treatment.