Rege-1 promotes C. elegans survival by modulating IIS and TOR pathways.

Metabolic pathways are known to sense the environmental stimuli and result in physiological adjustments. The responding processes need to be tightly controlled. Here, we show that upon encountering P. aeruginosa, C. elegans upregulate the transcription factor ets-4, but this upregulation is attenuated by the ribonuclease, rege-1. As such, mutants with defective REGE-1 ribonuclease activity undergo ets-4-dependent early death upon challenge with P. aeruginosa. Furthermore, mRNA-seq analysis revealed associated global changes in two key metabolic pathways, the IIS (insulin/IGF signaling) and TOR (target of rapamycin) kinase signaling pathways. In particular, failure to degrade ets-4 mRNA in activity-defective rege-1 mutants resulted in upregulation of class II longevity genes, which are suppressed during longevity, and activation of TORC1 kinase signaling pathway. Genetic inhibition of either pathway way was sufficient to abolish the poor survival phenotype in rege-1 worms. Further analysis of ETS-4 ChIP data from ENCODE and characterization of one upregulated class II gene, ins-7, support that the Class II genes are activated by ETS-4. Interestingly, deleting an upregulated Class II gene, acox-1.5, a peroxisome ß-oxidation enzyme, largely rescues the fat lost phenotype and survival difference between rege-1 mutants and wild-types. Thus, rege-1 appears to be crucial for animal survival due to its tight regulation of physiological responses to environmental stimuli. This function is reminiscent of its mammalian ortholog, Regnase-1, which modulates the intestinal mTORC1 signaling pathway.

Impaired cholesterol efflux in retinal pigment epithelium of individuals with juvenile macular degeneration.

Macular degeneration (MD) is characterized by the progressive deterioration of the macula and represents one of the most prevalent causes of blindness worldwide. Abnormal intracellular accumulation of lipid droplets and pericellular deposits of lipid-rich material in the retinal pigment epithelium (RPE) called drusen are clinical hallmarks of different forms of MD including Doyne honeycomb retinal dystrophy (DHRD) and age-related MD (AMD). However, the appropriate molecular therapeutic target underlying these disorder phenotypes remains elusive. Here, we address this knowledge gap by comparing the proteomic profiles of induced pluripotent stem cell (iPSC)-derived RPEs (iRPE) from individuals with DHRD and their isogenic controls. Our analysis and follow-up studies elucidated the mechanism of lipid accumulation in DHRD iRPE cells. Specifically, we detected significant downregulation of carboxylesterase 1 (CES1), an enzyme that converts cholesteryl ester to free cholesterol, an indispensable process in cholesterol export. CES1 knockdown or overexpression of EFEMP1R345W, a variant of EGF-containing fibulin extracellular matrix protein 1 that is associated with DHRD and attenuated cholesterol efflux and led to lipid droplet accumulation. In iRPE cells, we also found that EFEMP1R345W has a hyper-inhibitory effect on epidermal growth factor receptor (EGFR) signaling when compared to EFEMP1WT and may suppress CES1 expression via the downregulation of transcription factor SP1. Taken together, these results highlight the homeostatic role of cholesterol efflux in iRPE cells and identify CES1 as a mediator of cholesterol efflux in MD.

Efficient Sorting of Semiconducting Single-Walled Carbon Nanotubes in Bio-Renewable Solvents Through Main-Chain Engineering of Conjugated Polymers.

Conjugated polymer sorting is recognized as an efficient and scalable method for the selective extraction of semiconducting single-walled carbon nanotubes (s-SWCNTs). However, this process typically requires the use of nonpolar and aromatic solvents as the dispersion medium, which are petroleum-based and carry significant production hazards. Moreover, there is still potential for improving the efficiency of batch purification. Here, this study presents fluorene-based conjugated polymer that integrates diamines containing ethylene glycol chains (ODA) as linkers within the main chain, to effectively extract s-SWCNTs in bio-renewable solvents. The introduction of ODA segments enhances the solubility in bio-renewable solvents, facilitating effective wrapping of s-SWCNTs in polar environments. Additionally, the ODA within the main chain enhances affinity to s-SWCNTs, thereby contributing to increased yields and purity. The polymer achieves a high sorting yield of 55% and a purity of 99.6% in dispersion of s-SWCNTs in 2-Methyltetrahydrofuran. Thin-film transistor arrays fabricated with sorted s-SWCNTs solution through slot-die coating exhibit average charge carrier mobilities of 20-23 cm2 V⁻¹ s⁻¹ and high on/off current ratios exceeding 105 together with high spatial uniformity. This study highlights the viability of bio-renewable solvents in the sorting process, paving the way for the eco-friendly approach to the purification of SWCNTs.

Targeted therapy in glomerular diseases.

Targeted therapy has emerged as a more precise approach to treat glomerular diseases, focusing on specific molecular or cellular processes that contribute to disease development or progression. This approach complements or replaces traditional immunosuppressive therapy, optimizes supportive care, and provides a more personalized treatment strategy. In this review, we summarize the evolving understanding of pathogenic mechanisms in immune-mediated glomerular diseases and the developing targeted therapies based on these mechanisms. We begin by discussing pan-B-cell depletion, anti-CD20 rituximab, and targeting B-cell survival signaling through the BAFF/APRIL pathway. We also exam specific plasma cell depletion with anti-CD38 antibody. We then shift our focus to complement activation in glomerular diseases, which is involved in antibody-mediated glomerular diseases, such as IgA nephropathy, membranous nephropathy, ANCA-associated vasculitis, and lupus nephritis. Non-antibody-mediated complement activation occurs in glomerular diseases, including C3 glomerulopathy, complement-mediated atypical hemolytic uremic syndrome, and focal segmental glomerulosclerosis. We discuss specific inhibition of terminal, lectin, and alternative pathways in different glomerular diseases. Finally, we summarize current clinical trials targeting the final pathways of various glomerular diseases, including kidney fibrosis. We conclude that targeted therapy based on individualized pathogenesis should be the future of treating glomerular diseases.

CRISPR genome surgery in a novel humanized model for autosomal dominant retinitis pigmentosa.

Mutations in rhodopsin (RHO) are the most common causes of autosomal dominant retinitis pigmentosa (adRP), accounting for 20% to 30% of all cases worldwide. However, the high degree of genetic heterogeneity makes development of effective therapies cumbersome. To provide a universal solution to RHO-related adRP, we devised a CRISPR-based, mutation-independent gene ablation and replacement (AR) compound therapy carried by a dual AAV2/8 system. Moreover, we developed a novel hRHOC110R/hRHOWT humanized mouse model to assess the AR treatment in vivo. Results show that this humanized RHO mouse model exhibits progressive rod-cone degeneration that phenocopies hRHOC110R/hRHOWT patients. In vivo transduction of AR AAV8 dual vectors remarkably ablates endogenous RHO expression and overexpresses exogenous WT hRHO. Furthermore, the administration of AR during adulthood significantly hampers photoreceptor degeneration both histologically and functionally for at least 6 months compared with sole gene replacement or surgical trauma control. This study demonstrates the effectiveness of AR treatment of adRP in the human genomic context while revealing the feasibility of its application for other autosomal dominant disorders.

Prime Editing Strategy to Install the PRPH2 c.828+1G>A Mutation.

Mutations in peripherin 2 (PRPH2) are associated with a spectrum of inherited retinal diseases (IRDs) including retinitis pigmentosa (RP) and macular degeneration. As PRPH2 is localized to cone and rod outer segments, mutations in PRPH2 lead the disorganization or absence of photoreceptor outer segments. Here, we report on a patient with PRPH2-linked RP who exhibited widespread RPE atrophy with a central area of macular atrophy sparing the fovea. In future studies, we plan to model the pathobiology of PRPH2-based RP using induced pluripotent stem cell (iPSC)-derived retinal organoids. To effectively model rare mutations using iPSC-derived retinal organoids, we first require a strategy that can install the desired mutation in healthy wild-type iPSC, which can efficiently generate well-laminated retinal organoids. In this study, we developed an efficient prime editing strategy for the installation of the pathogenic PRPH2 c.828+1 G>A splice-site mutation underlying our patient's disease.

Generation of an Avian Myeloblastosis Virus (AMV) Reverse Transcriptase Prime Editor.

Prime editing (PE) is a novel, double-strand break (DSB)-independent gene editing technology that represents an exciting avenue for the treatment of inherited retinal diseases (IRDs). Given the extensive and heterogenous nature of the 280 genes associated with IRDs, genome editing has presented countless complications. However, recent advances in genome editing technologies have identified PE to have tremendous potential, with the capability to ameliorate small deletions and insertions in addition to all twelve possible transition and transversion mutations. The current PE system is based on the fusion of the Streptococcus pyogenes Cas9 (SpCas9) nickase H840A mutant and an optimized Moloney murine leukemia virus (MMLV) reverse-transcriptase (RT) in conjunction with a PE guide RNA (pegRNA). In this study, we developed a prime editor based on the avian myeloblastosis virus (AMV)-RT and showed its applicability for the installation of the PRPH2 c.828+1G>A mutation in HEK293 cells.

Sediment pollutant exposures caused hepatotoxicity and disturbed glycogenesis.

Liver metabolic syndrome, which involves impaired hepatic glycogen synthesis, is persistently increased by exposure to environmental pollutants. Most studies have investigated the pathogenesis of liver damage caused by single metal species or pure organics. However, under normal circumstances, the pollutants that we are exposed to are usually chemical mixtures that accumulate over time. Sediments are long-term repositories for environmental pollutants due to their environmental cycles, which make them good samples for evaluating the effect of environmental pollutants on the liver via bioaccumulation. This study aimed to clarify the effects of sediment pollutants on liver damage. Our results indicate that industrial wastewater sediment (downstream) is more cytotoxic than sediments from other zones. Downstream sediment extract (DSE) causes hepatotoxicity, stimulates reactive oxygen species (ROS) generation, triggers mitochondrial dysfunction, induces cell apoptosis, and results in the release of glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) proteins. Additionally, to elucidate the underlying mechanism by which sediment pollutants disturb hepatic glycogen synthesis, we investigated the effects of different sediment samples from different pollution situations on glycogen synthesis in liver cell lines. It was found that DSE induced multiple severe impairments in liver cells, and disturbed glycogen synthesis more than under other conditions. These impairments include decreased hepatic glycogen synthesis via inhibition and insulin receptor substrate 1 (IRS-1) /AKT /glycogen synthase kinase3ß (GSK3ß)-mediated glycogen synthase (GYS) inactivation. To our knowledge, this study provides the first detailed evidence of in vitro sediment-accumulated toxicity that interferes with liver glycogen synthesis, leading to hepatic cell damage through apoptosis.

Ultrasonography Facilitates the Diagnosis of Traumatic Iliopsoas Hemorrhage: A Report of Two Cases with Different Patterns.

We report two cases of traumatic iliopsoas hemorrhage, without hemoperitoneum, initially detected by ultrasound. Flexion hip contracture in the first case and incomplete femoral nerve palsy in the second case alerted the sonographer to the possibility of traumatic iliopsoas hemorrhage. The first case involved a 54-year-old man who complained of progressive right flank pain and difficulty in walking after falling to the ground. The second case involved a 34-year-old man who complained of severe lower back pain and numbness and weakness of the left leg after a motorcycle accident. In both cases, iliopsoas hemorrhage was confirmed on subsequent multidetector computed tomography.

Cr3+-Sphere Effect on the Whitlockite-Type NIR Phosphor Sr9Sc(PO4)7 with High Heat Dissipation for Digital Medical Applications.

The analysis of human body composition and food composition requires high-efficiency broadband near-infrared (NIR) lighting sources to achieve a portable, appropriately sized equipment. Herein, we develop a whitlockite-type NIR phosphor Sr9Sc(PO4)7:Cr3+ with an emission centered at 860 nm and full width at half-maximum of 147 nm. Due to the structural characteristics of the matrix, the 60 mol % Cr3+ substitution at the Sc3+ sites gives an internal quantum efficiency up to 56.5%. By replacing Sr with Ba and Ca, we observe a nontypical spectral shift phenomenon and discuss the influence of the second-sphere effect on octahedral Cr3+ ions. To evaluate the diagnostic application, we design a NIR ceramic device with a high optical power of 27.38 mW and high heat dissipation, which can decrease surface working temperature by nearly 50 °C for digital intraoral application. This study provides the research of the second-sphere coordination effect for selective octahedral sites such as Ca, Sr, and Ba coordinated by O atoms on a whitlockite-type crystal. Furthermore, the device promotes a nonionizing solution for detecting dental caries, tooth calcification, and diagnostic application.

Efficacy of a temporary CentriMag ventricular assist device in acute fulminant myocarditis patients revived with extracorporeal cardiopulmonary resuscitation.

BACKGROUND: Although extracorporeal life support (ECLS) can provide emergency systemic perfusion for acute fulminant myocarditis (AFM), the mortality rate remains extremely high, especially in those undergoing extracorporeal cardiopulmonary resuscitation (ECPR). Temporary ventricular assist device (VAD) can provide a more physiological blood flow direction and better subsequent organ perfusion than ECLS. We investigated temporary VAD efficacy in ECPR-revived AFM patients. METHODS: During January 2012-May 2019, we retrospectively recruited 22 AFM patients with hemodynamic collapse and ECPR; 11 underwent ECLS only and 11 underwent additional VAD support after ECLS. Systemic perfusion was compared via laboratory biochemistry at post-ECPR days 2 (D2) and 4 (D4). Consciousness and cardiac function were assessed through the Glasgow Coma Scale (GCS) and echocardiography, respectively. All major complications and causes of mortality were recorded; 30-day survival was analyzed and risk factors were predicted. RESULTS: The VAD group had significantly better hemodynamic improvement; more inotropes being tapered at D2 and D4; better data representative of systemic perfusion, including albumin, pH, bicarbonate, and lactate levels at D4; and better 30-day survival (72.7% vs. 27.2%, p = 0.033). The causes of mortality included central failure, multiple organ failure, and bacteremia with sepsis. The risk factors included lethal dysrhythmia before ECLS, GCS <5 at D2, and elevated cardiac enzymes at D4. CONCLUSION: For AFM patients, temporary VAD could provide better systemic perfusion and organ preservation than ECLS. VAD had better survival, including improved recovery and successful transplantation. Hence, temporary VAD should be considered if ECLS cannot revive the sustained cardiogenic shock.

Characterization of intracellular buffering power in human induced pluripotent stem cells and the loss of pluripotency is delayed by acidic stimulation and increase of NHE1 activity.

The homeostasis of intracellular pH (pHi ) affects many cellular functions. Our previous study has established a functional and molecular model of the active pHi regulators in human induced pluripotent stem cells (hiPSCs). The aims of the present study were to further quantify passive pHi buffering power (ß) and to investigate the effects of extracellular pH and Na+ -H+ exchanger 1 (NHE1) activity on pluripotency in hiPSCs. pHi was detected by microspectrofluorimetry with pH-sensitive dye-BCECF. Western blot, immunofluorescence staining, and flow cytometry were used to detect protein expression and pluripotency. Our study in hiPSCs showed that (a) the value of total (ßtot ), intrinsic (ßi ), and CO2 -dependent ( ßCO2 ) buffering power all increased while pHi increased; (b) during the spontaneous differentiation for 4 days, the ß values of ßtot and ßCO2 changed in a tendency of decrease, despite the absence of statistical significance; (c) an acidic cultured environment retained pluripotency and further upregulated expression and activity of NHE1 during spontaneous differentiation; (d) inhibition on NHE1 activity promoted the loss of pluripotency. In conclusion, we, for the first time, established a quantitative model of passive ß during differentiation and demonstrated that maintenance of NHE1 at a higher level was of critical importance for pluripotency retention in hiPSCs.

Perovskite Light-Emitting Electrochemical Cells Employing Electron Injection/Transport Layers of Ionic Transition Metal Complexes.

Recently, perovskites have attracted intense attention due to their high potential in optoelectronic applications. Employing perovskites as the emissive materials of light-emitting electrochemical cells (LECs) shows the advantages of simple fabrication process, low-voltage operation, and compatibility with inert electrodes, along with saturated electroluminescence (EL) emission. Unlike in previously reported perovskite LECs, in which salts are incorporated in the emissive layer, the ion-transport layer was separated from the emissive layer in this work. The layer of ionic transition metal complex (iTMC) not only provides mobile ions but also serves as an electron-injection/transport layer. Orthogonal solvents are used in spin coating to prevent the intermixing of stacked perovskite and iTMC layers. The blue iTMC with high ionization potential is effective in blocking holes from the emissive layer and thus ensures EL color saturation. In addition, the carrier balance of the perovskite/iTMC LECs can be optimized by adjusting the iTMC layer thickness. The optimized external quantum efficiency of the CsPbBr3 /iTMC LEC reaches 6.8 %, which is among the highest reported values for perovskite LECs. This work successfully demonstrates that, compared with mixing all components in a single emissive layer, separating the layer of ion transport, electron injection and transport from the perovskite emissive layer is more effective in adjusting device carrier balance. As such, solution-processable perovskite/iTMC LECs open up a new way to realize efficient perovskite LECs.

Perovskite Light-Emitting Electrochemical Cells Employing Electron Injection/Transport Layers of Ionic Transition Metal Complexes.

Invited for the cover of this issue are Chin-Wei Lu, Zu-Po Yang, Hai-Ching Su, and co-workers at National Yang Ming Chiao Tung University and Providence University. The image depicts electron transport for light-emitting electrochemical cells. Read the full text of the article at 10.1002/chem.202103739.

Proteomic and microbial assessments on the effect of Antrodia cinnamomea in C57BL/6 mice.

Antrodia cinnamomea (AC) is a nutraceutical fungus and studies have suggested that AC has the potential to prevent or alleviate diseases. However, little is known about the AC-induced phenotypes on the intestine-liver axis and gut microbial alterations. Here, we performed two-dimensional difference gel electrophoresis (2D-DIGE) and MALDI-Biotyper to elaborate the AC-induced phenotypes on the intestine-liver axis and gut microbial distribution of C57BL/6 mice. The experimental outcomes showed that the hepatic density may increase by elevating hepatic redox regulation, lipid degradation and glycolysis-related proteins and alleviating cholesterol biosynthesis and transport-related proteins in C57BL/6 mice with AC treatment. Moreover, AC facilitates intestinal glycolysis, TCA cycle, redox and cytoskeleton regulation-related proteins, but also reduces intestinal vesicle transport-related proteins in C57BL/6 mice. However, the body weight, GTT, daily food/water intake, and fecal/urine weight were unaffected by AC supplementation in C57BL/6 mice. Notably, the C57BL/6-AC mice had a higher gut microbial abundance of Alistipes shahii (AS) than C57BL/6-Ctrl mice. In summary, the AC treatment affects intestinal permeability by regulating redox and cytoskeleton-related proteins and elevates the gut microbial abundance of AS in C57BL/6 mice that might be associated with increasing hepatic density and metabolism-related proteins of the liver in C57BL/6 mice. Our study provides an insight into the mechanisms of AC-induced phenotypes and a comprehensive assessment of AC's nutraceutical effect in C57BL/6 mice.

Rhodium-Catalyzed Aerobic Decomposition of 1,3-Diaryl-2-diazo-1,3-diketones: Mechanistic Investigation and Application to the Synthesis of Benzils.

The conversion of 1,3-diaryl-2-diazo-1,3-diketones to 1,2-daryl-1,2-diketones (benzils) is reported based on a rhodium(II)-catalyzed aerobic decomposition process. The reaction occurs at ambient temperatures and can be catalyzed by a few dirhodium carboxylates (5 mol %) under a balloon pressure of oxygen. Moreover, an oxygen atom from the O2 reagent is shown to be incorporated into the product, and this is accompanied by the extrusion of a carbonyl unit from the starting materials. Mechanistically, it is proposed that the decomposition may proceed via the interaction of a ketene intermediate resulting from a Wolff rearrangement of the carbenoid, with a rhodium peroxide or peroxy radical species generated upon the activation of molecular oxygen. The proposed mechanism has been supported by the results from a set of controlled experiments. By using this newly developed strategy, a large array of benzil derivatives as well as 9,10-phenanthrenequinone were synthesized from the corresponding diazo substrates in varying yields. On the other hand, the method did not allow the generation of benzocyclobutene-1,2-dione from 2-diazo-1,3-indandione because of the difficulty of inducing the initial rearrangement.

The effect of temperature on the kinetics of enhanced amide bond formation from lactic acid and valine driven by deep eutectic solvents.

Deep eutectic solvents have been found to facilitate the copolymerization of hydroxy acids and amino acids through an ester-amide exchange reaction, and to drive the formation of amino acid-enriched oligomers with peptide backbones. The complexity of oligomer distribution is significantly reduced in deep eutectic solvents and amide-linked oligomers can be selectively produced. In the present study, we investigated the kinetics of amide bond formation in deep eutectic solvents to understand how the solvents regulate the pathways of complex copolymerization. A mathematical model successfully simulated the reaction of a lactic acid/valine mixture in deep eutectic solvents at different temperatures and provided insight into the activation energy of each step. Our findings indicated that the esterification and the evaporation of hydroxy acids were greatly suppressed in deep eutectic solvents because of the strong interaction between the quaternary ammonium salts and the hydroxy acids. In contrast, the ester-amide exchange reaction in deep eutectic solvents was significantly enhanced by lowering the activation entropies. The synergic effect of reduced esterification and increased exchange leads to amino acid-enriched oligomers with high yield and high selectivity. Furthermore, the reduced evaporation of hydroxy acids in deep eutectic solvents may preserve limited reactants in the prebiotic scenario. These results reveal deep eutectic solvents as sustainable media for the simple synthesis of amide bonds.

Ganoderma tsugae suppresses the proliferation of endometrial carcinoma cells via Akt signaling pathway.

Ganoderma is one of the common medicinal mushrooms in traditional Chinese medicine. Previous researches have unveiled the multifaceted biological activity of Ganoderma extract. Ganoderma tsugae has been investigated the potential on curing prostate, colon, lung, epidermoid, breast and ovarian cancers, but not including endometrial cancer. Endometrial cancer is a gynecological malignant tumor with serious drug resistance problem in clinical cancer treatment. This study aimed to demonstrate the first study of Ganoderma on treating endometrial cancer. The Ganoderma tsugae ethanol extract (GTEE) could suppress the proliferation of endometrial cancer cells HEC-1-A, KLE, and AN3 CA. GTEE also induced G1/S phase arrest and mitochondria-mediated apoptosis in endometrial cancer cells. Furthermore, the Akt signaling pathway could be suppressed by GTEE. Therefore, our results suggest for the first time that GTEE has the potential to be an adjuvant therapeutic agent in the treatment of endometrial cancer.

A Novel Relative High-Density Lipoprotein Index to Predict the Structural Changes in High-Density Lipoprotein and Its Ability to Inhibit Endothelial-Mesenchymal Transition.

Therapeutic elevation of high-density lipoprotein (HDL) is thought to minimize atherogenesis in subjects with dyslipidemia. However, this is not the case in clinical practice. The function of HDL is not determined by its concentration in the plasma but by its specific structural components. We previously identified an index for the prediction of HDL functionality, relative HDL (rHDL) index, and preliminarily explored that dysfunctional HDL (rHDL index value > 2) failed to rescue the damage to endothelial progenitor cells (EPCs). To confirm the effectiveness of the rHDL index for predicting HDL functions, here we evaluated the effects of HDL from patients with different rHDL index values on the endothelial-mesenchymal transition (EndoMT) of EPCs. We also analyzed the lipid species in HDL with different rHDL index values and investigated the structural differences that affect HDL functions. The results indicate that HDL from healthy adults and subjects with an rHDL index value < 2 protected transforming growth factor (TGF)-ß1-stimulated EndoMT by modulating Smad2/3 and Snail activation. HDL from subjects with an rHDL index value > 2 failed to restore the functionality of TGF-ß1-treated EPCs. Lipidomic analysis demonstrated that HDL with different rHDL index values may differ in the composition of triglycerides, phosphatidylcholine, and phosphatidylinositol. In conclusion, we confirmed the applicability of the rHDL index value to predict HDL function and found structural differences that may affect the function of HDL, which warrants further in-depth studies.

Effects of Levosimendan on Systemic Perfusion in Patients with Low Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) Score: Experience from a Single Center in Taiwan.

BACKGROUND: Patients with cardiogenic shock have a high risk of mortality. Intravenous levosimendan can provide pharmacologic inotrope support. OBJECTIVES: We aimed to investigate the effect of levosimendan in patients with extremely severe cardiogenic shock and low Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) score with or without mechanical circulatory support. METHODS: From January 2017 to May 2019, 24 patients with INTERMACS 1-4 were enrolled in this retrospective study. All patients had systemic malperfusion and were treated with levosimendan. Biochemistry data related to systemic perfusion were recorded and compared before and at 24 and 72 hours after levosimendan administration. Echocardiography and Kansas City Cardiomyopathy Questionnaire (KCCQ) were completed 2 months later to assess left ventricular ejection fraction (LVEF) and quality of life (QoL), respectively. RESULTS: Arterial pressure and heart rate did not significantly differ before and after levosimendan administration. Atrial fibrillation and ventricular premature complex increased without significance. The dose of inotropes could be significantly tapered down. There were no significant differences in blood urea nitrogen, creatinine, and lactate levels. Urine output significantly increased (p = 0.018), and liver-related enzymes improved but without significance. B-type natriuretic peptide significantly decreased (p = 0.007) at 24 hours after levosimendan administration. Echocardiography showed significantly improved LVEF 2 months later (22.43 ± 8.13% to 35.87 ± 13.4%, p = 0.001). KCCQ showed significantly improved physical activity and greater relief of symptoms (p = 0.003). The survival-to-discharge rate was 75%. CONCLUSIONS: We observed a decrease in B-type natriuretic peptide, better urine output, and alleviated hepatic injury in the levosimendan group. Most patients who survived without transplantation had significantly improved LVEF and better QoL after levosimendan administration.