Diversifying the anthracycline class of anti-cancer drugs identifies aclarubicin for superior survival of acute myeloid leukemia patients.

The efficacy of anthracycline-based chemotherapeutics, which include doxorubicin and its structural relatives daunorubicin and idarubicin, remains almost unmatched in oncology, despite a side effect profile including cumulative dose-dependent cardiotoxicity, therapy-related malignancies and infertility. Detoxifying anthracyclines while preserving their anti-neoplastic effects is arguably a major unmet need in modern oncology, as cardiovascular complications that limit anti-cancer treatment are a leading cause of morbidity and mortality among the 17 million cancer survivors in the U.S. In this study, we examined different clinically relevant anthracycline drugs for a series of features including mode of action (chromatin and DNA damage), bio-distribution, anti-tumor efficacy and cardiotoxicity in pre-clinical models and patients. The different anthracycline drugs have surprisingly individual efficacy and toxicity profiles. In particular, aclarubicin stands out in pre-clinical models and clinical studies, as it potently kills cancer cells, lacks cardiotoxicity, and can be safely administered even after the maximum cumulative dose of either doxorubicin or idarubicin has been reached. Retrospective analysis of aclarubicin used as second-line treatment for relapsed/refractory AML patients showed survival effects similar to its use in first line, leading to a notable 23% increase in 5-year overall survival compared to other intensive chemotherapies. Considering individual anthracyclines as distinct entities unveils new treatment options, such as the identification of aclarubicin, which significantly improves the survival outcomes of AML patients while mitigating the treatment-limiting side-effects. Building upon these findings, an international multicenter Phase III prospective study is prepared, to integrate aclarubicin into the treatment of relapsed/refractory AML patients.

Musashi orchestrates melanism in Laodelphax striatellus.

In insects, melanism, a fundamental pigmentation process, is of significant importance in evolutionary biology due to its complex genetic foundation. We investigated the role of the RNA-binding gene Musashi (msi) in melanism in Laodelphax striatellus, a Hemiptera species. We identified a single L. striatellus msi homolog, Lsmsi, encoding a 357 amino acid protein with 2 RNA recognition motifs. RNA interference-mediated knockdown of LsMsi resulted in complete body melanism and increased cuticular permeability. Additionally, we found the involvement of G protein-coupled receptor A42 and tyrosine hydroxylase (Th) in L. striatellus melanism. Knockdown of LsTh lightened the epidermis, showing dehydration signs, while LsA42 knockdown enhanced LsTh expression, leading to melanism. Surprisingly, Lsmsi knockdown decreased both LsA42 and LsTh expression, which was expected to cause whitening but resulted in melanism. Further, we found that Lsmsi influenced downstream genes like phenoloxidase homolog LsPo and dopa decarboxylase (Ddc) homolog LsDdc in the tyrosine-mediated melanism pathway. Extending to Nilaparvata lugens and Sogatella furcifera, we demonstrated the conserved role of msi in melanism among Delphacidae. Given MSI proteins' roles in cancer and tumors in vertebrates, our study is the first to link msi in insects to Delphacidae body color melanization via the tyrosine-mediated pathway, offering fresh perspectives on the genetic basis of insect melanism and msi functions.

Physiological and Structural Changes in Leaves of Platycrater arguta Seedlings Exposed to Increasing Light Intensities.

Understanding the light adaptation of plants is critical for conservation. Platycrater arguta, an endangered deciduous shrub endemic to East Asia, possesses high ornamental and phylogeographic value. However, the weak environmental adaptability of P. arguta species has limited its general growth and conservation. To obtain a deeper understanding of the P. arguta growth conditions, we examined the leaf morphology and physiology via anatomical and chloroplast ultrastructural analyses following exposure to different natural light intensities (full light, 40%, and 10%). The findings indicated that P. arguta seedings in the 10% light intensity had significantly improved leaf morphological characteristics and specific leaf area compared to those exposed to other intensities. The net photosynthetic rate, chlorophyll (Chl) content, photosynthetic nitrogen use efficiency (PNUE), and photosynthetic phosphorus use efficiency (PPUE) exhibited marked increases at a 10% light intensity compared to both 40% light and full light intensities, whereas the light compensation point and dark respiration levels reached their lowest values under the 10% light condition. With reduced light, leaf thickness, palisade tissue, spongy tissue, and stomatal density significantly decreased, whereas the stomatal length, stomatal width, and stomatal aperture were significantly elevated. When exposed to 10% light intensity, the ultrastructure of chloroplasts was well developed, chloroplasts and starch grain size, the number of grana, and thylakoids all increased significantly, while the number of plastoglobules was significantly reduced. Relative distance phenotypic plasticity index analysis exhibited that P. arguta adapts to varying light environments predominantly by adjusting PPUE, Chl b, PNUE, chloroplast area, and the activity of PSII reaction centers. We proposed that P. arguta efficiently utilizes low light to reconfigure its energy metabolism by regulating its leaf structure, photosynthetic capacity, nutrient use efficiency, and chloroplast development.

Response Mechanism of cbbM Carbon Sequestration Microbial Community Characteristics in Different Wetland Types in Qinghai Lake.

Carbon-sequestering microorganisms play an important role in the carbon cycle of wetland ecosystems. However, the response mechanism of carbon-sequestering microbial communities to wetland type changes and their relationship with soil carbon remain unclear. To explore these differences and identify the main influencing factors, this study selected marsh wetlands, river wetlands and lakeside wetlands around Qinghai Lake as research subjects. High-throughput sequencing was employed to analyze the functional gene cbbM of carbon-sequestering microorganisms. The results revealed that the alpha diversity of cbbM carbon-sequestering microorganisms mirrored the trend in total carbon content, with the highest diversity observed in marsh wetlands and the lowest in lakeside wetlands. The dominant bacterial phylum was Proteobacteria, with prevalent genera including Thiothrix, Acidithiobacillus, and Thiodictyon. Acidithiobacillus served as a biomarker in lakeside wetlands, while two other genera were indicative of marsh wetlands. The hierarchical partitioning analysis indicated that the diversity of cbbM carbon-fixing microorganisms was primarily influenced by the total nitrogen content, while the community structure was significantly affected by the soil total carbon content. Moreover, an increased soil temperature and humidity were found to favor the carbon fixation processes of Thiomicrospira, Thiomonas, Polaromonas, and Acidithiobacillus. In summary, changes in wetland types seriously affected the characteristics of cbbM carbon sequestration in microbial communities, and a warm and humid climate may be conducive to wetland carbon sequestration.

Characterisation of a Novel Insect-Specific Virus Discovered in Rice Thrips, Haplothrips aculeatus.

Insects constitute the largest proportion of animals on Earth and act as significant reservoirs and vectors in disease transmission. Rice thrips (Haplothrips aculeatus, family Phlaeothripidae) are one of the most common pests in agriculture. In this study, the full genome sequence of a novel Ollusvirus, provisionally named "Rice thrips ollusvirus 1" (RTOV1), was elucidated using transcriptome sequencing and the rapid amplification of cDNA ends (RACE). A homology search and phylogenetic tree analysis revealed that the newly identified virus is a member of the family Aliusviridae (order Jingchuvirales). The genome of RTOV1 contains four predicted open reading frames (ORFs), including a polymerase protein (L, 7590 nt), a glycoprotein (G, 4206 nt), a nucleocapsid protein (N, 2415 nt) and a small protein of unknown function (291 nt). All of the ORFs are encoded by the complementary genome, suggesting that the virus is a negative-stranded RNA virus. Phylogenetic analysis using polymerase sequences suggested that RTOV1 was closely related to ollusvirus 1. Deep small RNA sequencing analysis reveals a significant accumulation of small RNAs derived from RTOV1, indicating that the virus replicated in the insect. According to our understanding, this is the first report of an Ollusvirus identified in a member of the insect family Phlaeothripidae. The characterisation and discovery of RTOV1 is a significant contribution to the understanding of Ollusvirus diversity in insects.

Vertically Stacked Amorphous Ir/Ru/Ir Oxide Nanosheets for Boosted Acidic Water Splitting.

Integrating multiple functional components into vertically stacked heterostructures offers a prospective approach to manipulating the physicochemical properties of materials. The synthesis of vertically stacked heterogeneous noble metal oxides remains a challenge. Herein, we report a surface segregation approach to create vertically stacked amorphous Ir/Ru/Ir oxide nanosheets (NSs). Cross-sectional high-angle annular darkfield scanning transmission electron microscopy images demonstrate a three-layer heterostructure in the amorphous Ir/Ru/Ir oxide NSs, with IrOx layers located on the upper and lower surfaces, and a layer of RuOx sandwiched between the two IrOx layers. The vertically stacked heterostructure is a result of the diffusion of Ir atoms from the amorphous IrRuOx solid solution to the surface. The obtained A-Ir/Ru/Ir oxide NSs display an ultralow overpotential of 191 mV at 10 mA cm-2 toward acid oxygen evolution reaction and demonstrate excellent performance in a proton exchange membrane water electrolyzer, which requires only 1.63 V to achieve 1 A cm-2 at 60 °C, with virtually no activity decay observed after a 1300 h test.

Molecular and biological characterization of a bunyavirus infecting the brown planthopper (Nilaparvata lugens).

A negative-strand symbiotic RNA virus, tentatively named Nilaparvata lugens Bunyavirus (NLBV), was identified in the brown planthopper (BPH, Nilaparvata lugens). Phylogenetic analysis indicated that NLBV is a member of the genus Mobuvirus (family Phenuiviridae, order Bunyavirales). Analysis of virus-derived small interfering RNA suggested that antiviral immunity of BPH was successfully activated by NLBV infection. Tissue-specific investigation showed that NLBV was mainly accumulated in the fat-body of BPH adults. Moreover, NLBV was detected in eggs of viruliferous female BPHs, suggesting the possibility of vertical transmission of NLBV in BPH. Additionally, no significant differences were observed for the biological properties between NLBV-infected and NLBV-free BPHs. Finally, analysis of geographic distribution indicated that NLBV may be prevalent in Southeast Asia. This study provided a comprehensive characterization on the molecular and biological properties of a symbiotic virus in BPH, which will contribute to our understanding of the increasingly discovered RNA viruses in insects.

Cross-kingdom RNA interference mediated by insect salivary microRNAs may suppress plant immunity.

Communication between insects and plants relies on the exchange of bioactive molecules that traverse the species interface. Although proteinic effectors have been extensively studied, our knowledge of other molecules involved in this process remains limited. In this study, we investigate the role of salivary microRNAs (miRNAs) from the rice planthopper Nilaparvata lugens in suppressing plant immunity. A total of three miRNAs were confirmed to be secreted into host plants during insect feeding. Notably, the sequence-conserved miR-7-5P is specifically expressed in the salivary glands of N. lugens and is secreted into saliva, distinguishing it significantly from homologues found in other insects. Silencing miR-7-5P negatively affects N. lugens feeding on rice plants, but not on artificial diets. The impaired feeding performance of miR-7-5P-silenced insects can be rescued by transgenic plants overexpressing miR-7-5P. Through target prediction and experimental testing, we demonstrate that miR-7-5P targets multiple plant genes, including the immune-associated bZIP transcription factor 43 (OsbZIP43). Infestation of rice plants by miR-7-5P-silenced insects leads to the increased expression of OsbZIP43, while the presence of miR-7-5P counteracts this upregulation effect. Furthermore, overexpressing OsbZIP43 confers plant resistance against insects which can be subverted by miR-7-5P. Our findings suggest a mechanism by which herbivorous insects have evolved salivary miRNAs to suppress plant immunity, expanding our understanding of cross-kingdom RNA interference between interacting organisms.

IRF4-BLOC1S5: the first rearrangement gene identified in TEMPI syndrome.

Not available.

Identification and Functional Analysis of the fruitless Gene in a Hemimetabolous Insect, Nilaparvata lugens.

The fruitless (fru) gene functions as a crucial "tuner" in male insect courtship behavior through distinct expression patterns. In Nilaparvata lugens, our previous research showed doublesex (dsx) influencing male courtship songs, causing mating failures with virgin females. However, the impact of fru on N. lugens mating remains unexplored. In this study, the fru homolog (Nlfru) in N. lugens yielded four spliceosomes: Nlfru-374-a/b, Nlfru-377, and Nlfru-433, encoding proteins of 374aa, 377aa, and 433aa, respectively. Notably, only Nlfru-374b exhibited male bias, while the others were non-sex-specific. All NlFRU proteins featured the BTB conserved domain, with NlFRU-374 and NlFRU-377 possessing the ZnF domain with different sequences. RNAi-mediated Nlfru or its isoforms' knockdown in nymph stages blocked wing-flapping behavior in mating males, while embryonic knockdown via maternal RNAi resulted in over 80% of males losing wing-flapping ability, and female receptivity was reduced. Nlfru expression was Nldsx-regulated, and yet courtship signals and mating success were unaffected. Remarkably, RNAi-mediated Nlfru knockdown up-regulated the expression of flightin in macropterous males, which regulated muscle stiffness and delayed force response, suggesting Nlfru's involvement in muscle development regulation. Collectively, our results indicate that Nlfru functions in N. lugens exhibit a combination of conservation and species specificity, contributing insights into fru evolution, particularly in Hemiptera species.

The genomic history and global migration of a windborne pest.

Many insect pests, including the brown planthopper (BPH), undergo windborne migration that is challenging to observe and track. It remains controversial about their migration patterns and largely unknown regarding the underlying genetic basis. By analyzing 360 whole genomes from around the globe, we clarify the genetic sources of worldwide BPHs and illuminate a landscape of BPH migration showing that East Asian populations perform closed-circuit journeys between Indochina and the Far East, while populations of Malay Archipelago and South Asia undergo one-way migration to Indochina. We further find round-trip migration accelerates population differentiation, with highly diverged regions enriching in a gene desert chromosome that is simultaneously the speciation hotspot between BPH and related species. This study not only shows the power of applying genomic approaches to demystify the migration in windborne migrants but also enhances our understanding of how seasonal movements affect speciation and evolution in insects.

Transcriptome Analysis of Tomato Leaves Reveals Candidate Genes Responsive to Tomato Brown Rugose Fruit Virus Infection.

Tomato brown rugose fruit virus (ToBRFV) is a newly-emerging tobamovirus which was first reported on tomatoes in Israel and Jordan, and which has now spread rapidly in Asia, Europe, North America, and Africa. ToBRFV can overcome the resistance to other tobamoviruses conferred by tomato Tm-1, Tm-2, and Tm-22 genes, and it has seriously affected global crop production. The rapid and comprehensive transcription reprogramming of host plant cells is the key to resisting virus attack, but there have been no studies of the transcriptome changes induced by ToBRFV in tomatoes. Here, we made a comparative transcriptome analysis between tomato leaves infected with ToBRFV for 21 days and those mock-inoculated as controls. A total of 522 differentially expressed genes were identified after ToBRFV infection, of which 270 were up-regulated and 252 were down-regulated. Functional analysis showed that DEGs were involved in biological processes such as response to wounding, response to stress, protein folding, and defense response. Ten DEGs were selected and verified by qRT-PCR, confirming the reliability of the high-throughput sequencing data. These results provide candidate genes or signal pathways for the response of tomato leaves to ToBRFV infection.

Inhibition of Rice Stripe Virus Accumulation by Polyubiquitin-C in Laodelphax striatellus.

Many hosts utilize the ubiquitin system to defend against viral infection. As a key subunit of the ubiquitin system, the role of polyubiquitin in the viral infection of insects is unclear. Here, we identified the full-length cDNA of the polyubiquitin-C (UBC) gene in Laodelphax striatellus, the small brown planthopper (SBPH). LsUBC was expressed in various tissues and was highly expressed in salivary glands, midgut, and reproductive systems. Furthermore, the LsUBC expression profiles in the developmental stages showed that LsUBC was ubiquitously expressed in seven developmental stages and was highest expressed in female adults with SBPH. qRT-PCR analyses indicated that rice stripe virus (RSV) infection promoted the LsUBC expression. Knockdown of LsUBC mRNA via RNA interference increased RSV accumulation. These findings suggest that LsUBC inhibits RSV accumulation in L. striatellus.

Unveiling the Hidden Regulators: The Impact of lncRNAs on Zoonoses.

Zoonoses are diseases and infections naturally transmitted between humans and vertebrate animals. They form the dominant group of diseases among emerging infectious diseases and represent critical threats to global health security. This dilemma is largely attributed to our insufficient knowledge of the pathogenesis regarding zoonotic spillover. Long non-coding RNAs (lncRNAs) are transcripts with limited coding capacity. Recent technological advancements have enabled the identification of numerous lncRNAs in humans, animals, and even pathogens. An increasing body of literature suggests that lncRNAs function as key regulators in zoonotic infection. They regulate immune-related epigenetic, transcriptional, and post-transcriptional events across a broad range of organisms. In this review, we discuss the recent research progress on the roles of lncRNAs in zoonoses. We address the classification and regulatory mechanisms of lncRNAs in the interaction between host and zoonotic pathogens. Additionally, we explore the surprising function of pathogen-derived lncRNAs in mediating the pathogenicity and life cycle of zoonotic bacteria, viruses, and parasites. Understanding how these lncRNAs influence the zoonotic pathogenesis will provide important therapeutic insights to the prevention and control of zoonoses.

A Cell-Penetrating Peptide Improves Anti-HER2 Single-Chain Variable Fragment Internalization and Antitumor Activity against HER2-Positive Breast Cancer In Vitro and In Vivo.

Cell-penetrating peptides (CPPs) are invaluable tools for delivering various substances into cells by crossing biological membranes. However, the effects of cell-penetrating peptide fusion proteins on the biological activity of antibodies remain to be fully understood. Here, we engineered a recombinant protein, LP-scFv, which combines the single-chain variable region of anti-human epidermal growth factor receptor-2 with a novel and non-oxic cell-penetrating peptide as a leader peptide. The introduction of this leader peptide led to a more than twofold increase in the internalization efficiency of the single-chain antibody, as confirmed using microscopic analysis and flow cytometry. The effects of the single-chain antibodies and LP-scFv on cell viability were evaluated using the MTT assay. Both the single-chain antibodies and LP-scFv reduced the viability of BT474 and NCI-N87 cells in a dose-dependent manner while exhibiting minimal toxicity towards MCF-7 and MCF-10A cells. Further investigation into LP-scFv's mechanism revealed that the induced leader peptide does not alter the MAPK-ERK1/2 and PI3K/AKT pathways of single-chain antibodies. An enhanced antitumor activity was also confirmed in an NCI-N87 tumor xenograft model in mice with a reduction of 45.2% in tumor growth inhibition (vs. 23.1% for scFv) with a 50 mg/kg dose after orthotopic injection administration, which was equivalent to that of trastuzumab (vs. 55.7% for trastuzumab). Overall, these results indicate that LP-scFv exhibits significant permeation activity in HER2-positive cells to enhance the intracellular dose effect on antitumor activity in vitro and in vivo. This research lays the foundation for designing novel antibody-based therapies for cancer.

Exploring the relationships between pre-pregnancy BMI, gestational weight gain, and nutritional intake: a real-world investigation in Shandong, China.

This study investigated the associations between gestational weight gain (GWG), pre-pregnancy body mass index (BMI), and prenatal diet quality in pregnant women from Shandong, China. We analyzed a sample of 532 early-stage pregnant women registered at an outpatient clinic. Diet quality was evaluated using the Chinese Healthy Dietary Index for Pregnancy (CHDI-P), encompassing three dimensions: diversity, adequacy, and limitation, with an overall score out of 100. Dietary intake was documented via 24-h dietary recalls spanning three consecutive days and subsequently translated to a CHDI-P score. At the time of enrollment, BMI was measured on-site and classified as underweight (<18.5), normal weight (18.5-24.9), overweight (25.0-29.9), and obese (≥30.0). Pregnant women were also categorized into inadequate, adequate, and excessive weight gain groups based on their GWG. We employed a Tukey-adjusted generalized linear model to compare the CHDI-P scores between the pre-pregnancy BMI groups and GWG groups. The results revealed that the underweight group had significantly higher total scores and limitation total scores on the CHDI-P (p < 0.001). Conversely, the overweight and obese groups were more susceptible to suboptimal dietary quality. Notably, the inadequate weight gain group displayed significantly elevated food adequacy scores compared to the other two groups (p < 0.05). This indicates that greater GWGs do not necessarily align with principles of adequate nutrition.

Maintenance of persistent transmission of a plant arbovirus in its insect vector mediated by the Toll-Dorsal immune pathway.

Throughout evolution, arboviruses have developed various strategies to counteract the host's innate immune defenses to maintain persistent transmission. Recent studies have shown that, in addition to bacteria and fungi, the innate Toll-Dorsal immune system also plays an essential role in preventing viral infections in invertebrates. However, whether the classical Toll immune pathway is involved in maintaining the homeostatic process to ensure the persistent and propagative transmission of arboviruses in insect vectors remain unclear. In this study, we revealed that the transcription factor Dorsal is actively involved in the antiviral defense of an insect vector (Laodelphax striatellus) by regulating the target gene, zinc finger protein 708 (LsZN708), which mediates downstream immune-related effectors against infection with the plant virus (Rice stripe virus, RSV). In contrast, an antidefense strategy involving the use of the nonstructural-protein (NS4) to antagonize host antiviral defense through competitive binding to Dorsal from the MSK2 kinase was employed by RSV; this competitive binding inhibited Dorsal phosphorylation and reduced the antiviral response of the host insect. Our study revealed the molecular mechanism through which Toll-Dorsal-ZN708 mediates the maintenance of an arbovirus homeostasis in insect vectors. Specifically, ZN708 is a newly documented zinc finger protein targeted by Dorsal that mediates the downstream antiviral response. This study will contribute to our understanding of the successful transmission and spread of arboviruses in plant or invertebrate hosts.

Universal Synthesis of Amorphous Metal Oxide Nanomeshes.

Constructing the pore structures in amorphous metal oxide nanosheets can enhance their electrocatalytic performance by efficiently increasing specific surface areas and facilitating mass transport in electrocatalysis. However, the accurate synthesis for porous amorphous metal oxide nanosheets remains a challenge. Herein, a facile nitrate-assisted oxidation strategy is reported for synthesizing amorphous mesoporous iridium oxide nanomeshes (a-m IrOx NMs) with a pore size of ∼4 nm. X-ray absorption characterizations indicate that a-m IrOx NMs possess stretched Ir─O bonds and weaker Ir-O interaction compared with commercial IrO2. Combining thermogravimetric-fourier transform infrared spectroscopy with differential scanning calorimetry measurements, it is demonstrated that sodium nitrate, acting as an oxidizing agent, is conducive to the formation of amorphous nanosheets, while the NO2 produced by the in situ decomposition of nitrates facilitates the generation of pores within the nanomeshes. As an anode electrocatalyst in proton exchange membrane water electrolyzer, a-m IrOx NMs exhibit superior performance, maintaining a cell voltage of 1.67 V at 1 A cm-2 for 120 h without obvious decay with a low loading (0.4 mgcatalyst cm-2). Furthermore, the nitrate-assisted method is demonstrated to be a general approach to prepare various amorphous metal oxide nanomeshes, including amorphous RhOx, TiOx, ZrOx, AlOx, and HfOx nanomeshes.

Salivary proteins potentially derived from horizontal gene transfer are critical for salivary sheath formation and other feeding processes.

Herbivorous insects employ an array of salivary proteins to aid feeding. However, the mechanisms behind the recruitment and evolution of these genes to mediate plant-insect interactions remain poorly understood. Here, we report a potential horizontal gene transfer (HGT) event from bacteria to an ancestral bug of Eutrichophora. The acquired genes subsequently underwent duplications and evolved through co-option. We annotated them as horizontal-transferred, Eutrichophora-specific salivary protein (HESPs) according to their origin and function. In Riptortus pedestris (Coreoidea), all nine HESPs are secreted into plants during feeding. The RpHESP4 to RpHESP8 are recently duplicated and found to be indispensable for salivary sheath formation. Silencing of RpHESP4-8 increases the difficulty of R. pedestris in probing the soybean, and the treated insects display a decreased survivability. Although silencing the other RpHESPs does not affect the salivary sheath formation, negative effects are also observed. In Pyrrhocoris apterus (Pyrrhocoroidea), five out of six PaHESPs are secretory salivary proteins, with PaHESP3 being critical for insect survival. The PaHESP5, while important for insects, no longer functions as a salivary protein. Our results provide insight into the potential origin of insect saliva and shed light on the evolution of salivary proteins.

Cardiac effects of deferasirox in transfusion-dependent patients with myelodysplastic syndromes: TELESTO study.

Iron overload from repeated transfusions has a negative impact on cardiac function, and iron chelation therapy may help prevent cardiac dysfunction in transfusion-dependent patients with myelodysplastic syndromes (MDS). TELESTO (NCT00940602) was a prospective, placebo-controlled, randomised study to evaluate the iron chelator deferasirox in patients with low- or intermediate-1-risk MDS and iron overload. Echocardiographic parameters were collected at screening and during treatment. Patients receiving deferasirox experienced a significant decrease in the composite risk of hospitalisation for congestive heart failure (CHF) or worsening of cardiac function (HR = 0.23; 95% CI: 0.05, 0.99; nominal p = 0.0322) versus placebo. No significant differences between the arms were found in left ventricular ejection fraction, ventricular diameter and mass or pulmonary artery pressure. The absolute number of events was low, but the enrolled patients were younger than average for patients with MDS, with no serious cardiac comorbidities and a modest cardiovascular risk profile. These results support the effectiveness of deferasirox in preventing cardiac damage caused by iron overload in this patient population. Identification of patients developing CHF is challenging due to the lack of distinctive echocardiographic features. The treatment of iron overload may be important to prevent cardiac dysfunction in these patients, even those with moderate CHF risk.