Bitter taste receptor activation by cholesterol and an intracellular tastant.

Bitter taste sensing is mediated by type 2 taste receptors (TAS2Rs (also known as T2Rs)), which represent a distinct class of G-protein-coupled receptors1. Among the 26 members of the TAS2Rs, TAS2R14 is highly expressed in extraoral tissues and mediates the responses to more than 100 structurally diverse tastants2-6, although the molecular mechanisms for recognizing diverse chemicals and initiating cellular signalling are still poorly understood. Here we report two cryo-electron microscopy structures for TAS2R14 complexed with Ggust (also known as gustducin) and Gi1. Both structures have an orthosteric binding pocket occupied by endogenous cholesterol as well as an intracellular allosteric site bound by the bitter tastant cmpd28.1, including a direct interaction with the α5 helix of Ggust and Gi1. Computational and biochemical studies validate both ligand interactions. Our functional analysis identified cholesterol as an orthosteric agonist and the bitter tastant cmpd28.1 as a positive allosteric modulator with direct agonist activity at TAS2R14. Moreover, the orthosteric pocket is connected to the allosteric site via an elongated cavity, which has a hydrophobic core rich in aromatic residues. Our findings provide insights into the ligand recognition of bitter taste receptors and suggest activities of TAS2R14 beyond bitter taste perception via intracellular allosteric tastants.

Molecular basis for selective activation of DREADD-based chemogenetics.

Designer receptors exclusively activated by designer drugs (DREADDs) represent a powerful chemogenetic technology for the remote control of neuronal activity and cellular signalling1-4. The muscarinic receptor-based DREADDs are the most widely used chemogenetic tools in neuroscience research. The Gq-coupled DREADD (hM3Dq) is used to enhance neuronal activity, whereas the Gi/o-coupled DREADD (hM4Di) is utilized to inhibit neuronal activity5. Here we report four DREADD-related cryogenic electron microscopy high-resolution structures: a hM3Dq-miniGq complex and a hM4Di-miniGo complex bound to deschloroclozapine; a hM3Dq-miniGq complex bound to clozapine-N-oxide; and a hM3R-miniGq complex bound to iperoxo. Complemented with mutagenesis, functional and computational simulation data, our structures reveal key details of the recognition of DREADD chemogenetic actuators and the molecular basis for activation. These findings should accelerate the structure-guided discovery of next-generation chemogenetic tools.

Structure, function and pharmacology of human itch GPCRs.

The MRGPRX family of receptors (MRGPRX1-4) is a family of mas-related G-protein-coupled receptors that have evolved relatively recently1. Of these, MRGPRX2 and MRGPRX4 are key physiological and pathological mediators of itch and related mast cell-mediated hypersensitivity reactions2-5. MRGPRX2 couples to both Gi and Gq in mast cells6. Here we describe agonist-stabilized structures of MRGPRX2 coupled to Gi1 and Gq in ternary complexes with the endogenous peptide cortistatin-14 and with a synthetic agonist probe, respectively, and the development of potent antagonist probes for MRGPRX2. We also describe a specific MRGPRX4 agonist and the structure of this agonist in a complex with MRGPRX4 and Gq. Together, these findings should accelerate the structure-guided discovery of therapeutic agents for pain, itch and mast cell-mediated hypersensitivity.

Ligand recognition and allosteric modulation of the human MRGPRX1 receptor.

The human MAS-related G protein-coupled receptor X1 (MRGPRX1) is preferentially expressed in the small-diameter primary sensory neurons and involved in the mediation of nociception and pruritus. Central activation of MRGPRX1 by the endogenous opioid peptide fragment BAM8-22 and its positive allosteric modulator ML382 has been shown to effectively inhibit persistent pain, making MRGPRX1 a promising target for non-opioid pain treatment. However, the activation mechanism of MRGPRX1 is still largely unknown. Here we report three high-resolution cryogenic electron microscopy structures of MRGPRX1-Gαq in complex with BAM8-22 alone, with BAM8-22 and ML382 simultaneously as well as with a synthetic agonist compound-16. These structures reveal the agonist binding mode for MRGPRX1 and illuminate the structural requirements for positive allosteric modulation. Collectively, our findings provide a molecular understanding of the activation and allosteric modulation of the MRGPRX1 receptor, which could facilitate the structure-based design of non-opioid pain-relieving drugs.

Biosafety of human environments can be supported by effective use of renewable biomass.

Preventing pathogenic viral and bacterial transmission in the human environment is critical, especially in potential outbreaks that may be caused by the release of ancient bacteria currently trapped in the permafrost. Existing commercial disinfectants present issues such as a high carbon footprint. This study proposes a sustainable alternative, a bioliquid derived from biomass prepared by hydrothermal liquefaction. Results indicate a high inactivation rate of pathogenic virus and bacteria by the as-prepared bioliquid, such as up to 99.99% for H1N1, H5N1, H7N9 influenza A virus, and Bacillus subtilis var. niger spores and 99.49% for Bacillus anthracis Inactivation of Escherichia coli and Staphylococcus epidermidis confirmed that low-molecular-weight and low-polarity compounds in bioliquid are potential antibacterial components. High temperatures promoted the production of antibacterial substances via depolymerization and dehydration reactions. Moreover, bioliquid was innoxious as confirmed by the rabbit skin test, and the cost per kilogram of the bioliquid was $0.04427, which is notably lower than that of commercial disinfectants. This study demonstrates the potential of biomass to support our biosafety with greater environmental sustainability.

Sustainable Biomass Acts as an Electron Donor for Cr(VI) Reduction during the Subcritical Hydrothermal Process: Molecular Insights into the Role of Hydrochar and Liquid Compounds.

Heavy metal pollution is a critical environmental issue that has garnered significant attention from the international community. Subcritical hydrothermal liquefaction (HTL) as an emerging green technology has demonstrated remarkable promise in environmental remediation. However, there is limited research on the remediation of highly toxic Cr(VI) using HTL. This study reveals that the HTL reaction of biomass enables the simultaneous reduction and precipitation of Cr(VI). At 280 °C, the reduction of Cr(VI) was nearly complete, with a high reduction rate of 98.9%. The reduced Cr as Cr(OH)3 and Cr2O3 was primarily enriched in hydrochar, accounting for over 99.9% of the total amount. This effective enrichment resulted in the removal of Cr(VI) from the aqueous phase while simultaneously yielding clean liquid compounds like organic acids and furfural. Furthermore, the elevated temperature facilitated the formation of Cr(III) and enhanced its accumulation within hydrochar. Notably, the resulting hydrochar and small oxygenated compounds, especially aldehyde, served as electron donors for Cr(VI) reduction. Additionally, the dissolved Cr facilitated the depolymerization and deoxygenation processes of macromolecular compounds with lignin-like structures, leading to more small oxygenated compounds and subsequently influencing Cr(VI) reduction. These findings have substantial implications for green and sustainable development.

Viral and Bacterial Community Dynamics in Food Waste and Digestate from Full-Scale Biogas Plants.

Anaerobic digestion (AD) is commonly used in food waste treatment. Prokaryotic microbial communities in AD of food waste have been comprehensively studied. The role of viruses, known to affect microbial dynamics and metabolism, remains largely unexplored. This study employed metagenomic analysis and recovered 967 high-quality viral bins within food waste and digestate derived from 8 full-scale biogas plants. The diversity of viral communities was higher in digestate. In silico predictions linked 20.8% of viruses to microbial host populations, highlighting possible virus predators of key functional microbes. Lineage-specific virus-host ratio varied, indicating that viral infection dynamics might differentially affect microbial responses to the varying process parameters. Evidence for virus-mediated gene transfer was identified, emphasizing the potential role of viruses in controlling the microbiome. AD altered the specific process parameters, potentially promoting a shift in viral lifestyle from lysogenic to lytic. Viruses encoding auxiliary metabolic genes (AMGs) were involved in microbial carbon and nutrient cycling, and most AMGs were transcriptionally expressed in digestate, meaning that viruses with active functional states were likely actively involved in AD. These findings provided a comprehensive profile of viral and bacterial communities and expanded knowledge of the interactions between viruses and hosts in food waste and digestate.

Syntrophic propionate degradation in anaerobic digestion facilitated by hydrochar: Microbial insights as revealed by genome-centric metatranscriptomics.

Propionate is a model substrate for studying energy-limited syntrophic communities in anaerobic digestion, and syntrophic bacteria usually catalyze its degradation in syntrophy with methanogens. In the present study, metagenomics and metatranscriptomics were used to study the effect of the supportive material (e.g., hydrochar) on the key members of propionate degradation and their cooperation mechanism. The results showed that hydrochar increased the methane production rate (up to 57.1%) from propionate. The general transcriptional behavior of the microbiome showed that both interspecies H2 transfer (IHT) and direct interspecies electron transfer (DIET) played essential roles in the hydrochar-mediated methanation of propionate. Five highly active syntrophic propionate-oxidizing bacteria were identified by genome-centric metatranscriptomics. H85pel, a member of the family Pelotomaculaceae, was specifically enriched by hydrochar. Hydrochar enhanced the expression of the flagellum subunit, which interacted with methanogens and hydrogenases in H85pel, indicating that IHT was one of the essential factors promoting propionate degradation. Hydrochar also enriched H162tha belonging to the genus of Thauera. Hydrochar induced the expression of genes related to the complete propionate oxidation pathway, which did not produce acetate. Hydrochar and e-pili-mediated DIET were enhanced, which was another factor promoting propionate degradation. These findings improved the understanding of metabolic traits and cooperation between syntrophic propionate oxidizing bacteria (SPOB) and co-metabolizing partners and provided comprehensive transcriptional insights on function in propionate methanogenic systems.

Systematic DOE Approach for Dry Granulation Study at Early Clinical Stage of Novel Drugs: An Industrial Case.

In order to introduce a cost-effective strategy method for commercial scale dry granulation at the early clinical stage of drug product development, we developed dry granulation process using formulation without API, fitted and optimized the process parameters adopted Design of Experiment (DOE). Then, the process parameters were confirmed using one formulation containing active pharmaceutical ingredient (API). The results showed that the roller pressure had significant effect on particle ratio (retained up to #60 mesh screen), bulk density and tapped density. The roller gap had significant influence on particle ratio and specific energy. The particle ratio was significantly affected by the mill speed (second level). The tabletability of the powder decreased after dry granulation. The effect of magnesium stearate on the tabletability was significant. In the process validation study, the properties of the prepared granules met the requirements for each response studied in the DOE. The prepared tablets showed higher tensile strength, good content uniformity of filled capsules, and the dissolution profiles of which were consistent with that of clinical products. This drug product process development and research strategies could be used as a preliminary experiment for the dry granulation process in the early clinical stage.

Comparative Analysis of Codon Usage Bias in Six Eimeria Genomes.

The codon usage bias (CUB) of genes encoded by different species' genomes varies greatly. The analysis of codon usage patterns enriches our comprehension of genetic and evolutionary characteristics across diverse species. In this study, we performed a genome-wide analysis of CUB and its influencing factors in six sequenced Eimeria species that cause coccidiosis in poultry: Eimeria acervulina, Eimeria necatrix, Eimeria brunetti, Eimeria tenella, Eimeria praecox, and Eimeria maxima. The GC content of protein-coding genes varies between 52.67% and 58.24% among the six Eimeria species. The distribution trend of GC content at different codon positions follows GC1 > GC3 > GC2. Most high-frequency codons tend to end with C/G, except in E. maxima. Additionally, there is a positive correlation between GC3 content and GC3s/C3s, but a significantly negative correlation with A3s. Analysis of the ENC-Plot, neutrality plot, and PR2-bias plot suggests that selection pressure has a stronger influence than mutational pressure on CUB in the six Eimeria genomes. Finally, we identified from 11 to 15 optimal codons, with GCA, CAG, and AGC being the most commonly used optimal codons across these species. This study offers a thorough exploration of the relationships between CUB and selection pressures within the protein-coding genes of Eimeria species. Genetic evolution in these species appears to be influenced by mutations and selection pressures. Additionally, the findings shed light on unique characteristics and evolutionary traits specific to the six Eimeria species.

Neurotensin Receptor Allosterism Revealed in Complex with a Biased Allosteric Modulator.

The NTSR1 neurotensin receptor (NTSR1) is a G protein-coupled receptor (GPCR) found in the brain and peripheral tissues with neurotensin (NTS) being its endogenous peptide ligand. In the brain, NTS modulates dopamine neuronal activity, induces opioid-independent analgesia, and regulates food intake. Recent studies indicate that biasing NTSR1 toward ß-arrestin signaling can attenuate the actions of psychostimulants and other drugs of abuse. Here, we provide the cryoEM structures of NTSR1 ternary complexes with heterotrimeric Gq and GoA with and without the brain-penetrant small-molecule SBI-553. In functional studies, we discovered that SBI-553 displays complex allosteric actions exemplified by negative allosteric modulation for G proteins that are Gα subunit selective and positive allosteric modulation and agonism for ß-arrestin translocation at NTSR1. Detailed structural analysis of the allosteric binding site illuminated the structural determinants for biased allosteric modulation of SBI-553 on NTSR1.

Iron Deficiency Might Impair the Recovery of Left Ventricular Function after Surgical Revascularization in Diabetic Patients: A Retrospective Study.

Background: Iron deficiency (ID) is one of the most common micronutrient deficiencies affecting public health. Studies show that ID affects the prognosis of patients with heart disease, including heart failure, coronary artery disease and myocardial infarction. However, there is limited information regarding the impact of ID on patients undergoing cardiac surgery. This study aimed to evaluate the influence of preoperative ID on the prognosis of type 2 diabetes mellitus (T2DM) patients undergoing coronary artery bypass grafting (CABG). Methods: In the Glycemic control using mobile-based intervention in patients with diabetes undergoing coronary artery bypass to promote self-management (GUIDEME) study, patients with T2DM undergoing CABG were prospectively recruited. In this study, only those patients with preoperative iron metabolism results were enrolled. Patients were grouped based on the presence of preoperative ID. The primary endpoint was defined as the significant improvement of follow-up ejection fraction (EF) compared to postoperative levels (classified according to the 75th percentile of the change, and defined as an improvement of greater than or equal to 5%). Univariable logistic regression was performed to explore the potential confounders, followed by multiple adjustment. Results: A total of 302 patients were enrolled. No deaths were observed during the study period. A higher incidence of the primary endpoint was observed in the ID group (25.4% vs 12.9%, p = 0.015). The postoperative and follow-up EF were similar beween the two groups. In the regression analysis, ID was noticed to be a strong predictor against the significant improvement of EF in both univariable (odds ratio [OR]: 0.44, 95% confidence interval [CI]: 0.22-0.86, p = 0.017) and multivariable (OR: 0.43, 95% CI: 0.24-0.98, p = 0.043) logistic regression. In the subgroup analysis, ID was a predictor of significant improvement of EF in age ≤ 60 years, male, EF ≤ 60%, and on-pump CABG patients. Conclusions: In T2DM patients undergoing CABG, ID might negatively affect the early recovery of left ventricular systolic function in terms of recovery of EF 3-6 months after surgery, especially in patients age ≤ 60 years, males, EF ≤ 60% and in those undergoing on-pump CABG.

In Situ N, O Co-Doped Nanoporous Carbon Derived from Mixed Egg and Rice Waste as Green Supercapacitor.

The conversion of nitrogen-oxygen-rich biomass wastes into heteroatomic co-doped nanostructured carbons used as energy storage materials has received widespread attention. In this study, an in situ nitrogen-oxygen co-doped porous carbon was prepared for supercapacitor applications via a two-step method of pre-carbonization and pyrolytic activation using mixed egg yolk/white and rice waste. The optimal sample (YPAC-1) was found to have a 3D honeycomb structure composed of abundant micropores and mesopores with a high specific surface area of 1572.1 m2 g-1, which provided abundant storage space and a wide transport path for electrolyte ions. Notably, the specific capacitance of the constructed three-electrode system was as high as 446.22 F g-1 at a current density of 1 A g-1 and remained above 50% at 10 A g-1. The capacitance retention was 82.26% after up to 10,000 cycles. The symmetrical capacitor based on YPAC-1 with a two-electrode structure exhibited an energy density of 8.3 Wh kg-1 when the power density was 136 W kg-1. These results indicate that porous carbon materials prepared from mixed protein and carbohydrate waste have promising applications in the field of supercapacitors.

Novel Long-Chain Fatty Acid (LCFA)-Degrading Bacteria and Pathways in Anaerobic Digestion Promoted by Hydrochar as Revealed by Genome-Centric Metatranscriptomics Analysis.

A large amount of long-chain fatty acids (LCFA) are generated after lipids hydrolysis in anaerobic digestion (AD), and LCFA are difficult to be biodegraded. This study showed that hydrochar (HC), which was produced during the hydrothermal liquefaction of organic wastes, significantly increased the methane production rate (by 56.9%) of oleate, a typical refractory model LCFA. Genomic-centric metatranscriptomics analysis revealed that three novel microbes (Bin138 Spirochaetota sp., Bin35 Smithellaceae sp., and Bin54 Desulfomonilia sp.) that were capable of degrading LCFA were enriched by HC, which played an important role in the degradation of oleate. LCFA was degraded to acetate through the well-known LCFA ß-oxidation pathway and the combined ß-oxidation and butyrate oxidation pathway. In addition, it was found that HC promoted the direct interspecies electron transfer (DIET) between Methanothrix sp. and Bin54 Desulfomonilia sp. The enriched new types of LCFA-degrading bacteria and the promotion of DIET contributed to the improved methane production rate of oleate by HC. IMPORTANCE Long-chain fatty acids (LCFA) are difficult to be degraded in anaerobic digestion (AD), and the known LCFA degrading bacteria are only limited to the families Syntrophomonadaceae and Syntrophaceae. Here, we found that hydrochar effectively promoted AD of LCFA, and the new LCFA-degrading bacteria and a new metabolic pathway were also revealed based on genomic-centric metatranscriptomic analysis. This study provided a new method for enhancing the AD of organic wastes with high content of LCFA and increased the understanding of the microbes and their metabolic pathways involved in AD of LCFA.

Real-time measurement and control of nanofiber diameters using a femtowatt photodetector.

Real-time measurement and control of optical nanofiber diameters are of particular importance in many applications. Here, we propose and demonstrate a novel and simple method to control the nanofiber diameters in real time, which is based on monitoring the intensity of light scattered from the evanescent field using a femtowatt photodetector. Our experimental results show that the ultra-high precision is within 3 nm and accuracy is within 10 nm in the control of diameters ranging from 400 nm to 750 nm. Our method is also universal and can be extended to optical fibers with other wavelengths.

Serological investigation of Gyrovirus homsa1 infections in chickens in China.

BACKGROUND: Gyrovirus homsa1 (GyH1) (also known as Gyrovirus 3, GyV3) is a non-enveloped, small, single-stranded DNA virus, which was first identified in children with acute diarrhea, and was subsequently detected in marketed chickens, broilers with transmissible viral proventriculitis (TVP), and mammals. GyH1 is a pathogenic virus in chickens, causing aplastic anemia, immunosuppression, and multisystem damage. However, the seroepidemiology of GyH1 infection in chickens remains unclear. Here, we investigated the seroprevalence of GyH1 in chickens by ELISA to reveal the endemic status of GyH1 in China. RESULTS: An indirect ELISA with high sensitivity and specificity was developed for investigation of seroepidemiology of GyH1 in chickens in China. The seropositive rate of GyH1 ranged from 0.6% to 7.7% in thirteen provinces, and ranged from 4.1% to 8.1% in eight species chickens. The seropositive rate of GyH1 in broiler breeders was significantly higher than that of in layers. There was a negative correlation between seropositive rate and age of chickens. The highest and lowest seropositive rate were present in chickens at 30-60 days and over 180 days, respectively. CONCLUSIONS: The seroepidemiological investigation results demonstrated that natural GyH1 infection is widespread in chickens in China. Different species showed different susceptibility for GyH1. Aged chickens showed obvious age-resistance to GyH1. GyH1 has shown a high risk to the poultry industry and should be highly concerned.

Relationship between energy balance-related behaviors and personal and family factors in overweight/obese primary school students aged 10-12 years in China: a cross-sectional study.

BACKGROUND: Increasing rates of childhood obesity worldwide are a serious threat to the health of school-aged children. Unhealthy behavioral habits are modifiable factors in the control of childhood obesity, and personal and family factors are key influencing factors of behavioral habits in school-aged children. This study assessed the relationship between overweight/obesity, energy balance-related behaviors (EBRB), and their influencing factors in school-aged children. METHODS: This cross-sectional survey included 4412 primary school-aged (10-12 years) students who underwent body tests and were selected through stratified sampling in the Northeast, North, Northwest, and Southwest regions of China from March to July 2021. Independent sample t test was used to compare differences between behaviors and influencing factors of energy balance among overweight/obesity and normal weight students. Logistic regression analysis was used to assess the influence of EBRB on body shape. Multiple linear regression was used to assess the influence of personal and family factors on EBRB effects. RESULTS: Compared with normal-weight students, number of breakfasts consumed per week by overweight/obese students was significantly lower (p < 0.01), and weekly screen-viewing time was significantly longer (p < 0.01). Overweight/obese students' health beliefs, parental subjective norms, parental modelling, parental practices, and home availability scores increased significantly in terms of beverage consumption behavior (p < 0.01 or p < 0.05). Attitude, health beliefs, self-efficacy, parental subjective norms, and parental support scores decreased significantly in terms of breakfast consumption (p < 0.01 or p < 0.05). Health belief scores on physical activity increased significantly (p < 0.01), while preference and autonomy scores decreased significantly (p < 0.01). Health beliefs, parental subjective norms, and parental practices scores of screen-viewing activities increased significantly (p < 0.01 or p < 0.05). Breakfast consumption (odds ratio [OR]: 0.911; 95% confidence interval [CI]: 0.870-0.954) and screen-viewing activities (OR:1.055; 95% CI: 1.030-1.080) correlated negatively and positively with overweight/obesity, respectively. The main influencing factors of breakfast behavior in overweight/obese students were self-efficacy (0.14), preference (0.11), attitude (0.07), home availability (0.18), and parent modelling (0.09); those for screen-viewing behavior were preference (0.19), self-efficacy (- 0.15), parental practices (0.13), and parental subjective norm (0.12). CONCLUSIONS: Irregular breakfast consumption and excessive screen-viewing time are key EBRB associated with overweight/obesity among these Chinese participants. Their unhealthy breakfast consumption and screen-viewing activities result from a combination of personal and family factors.

Is 3-6 months anticoagulation with warfarin necessary after left ventricular thrombectomy with left ventricular aneurysm surgery?

OBJECTIVES: No recommendation exists on the optimal antithrombotic therapy after left ventricular thrombus (LVT) resection in the current guidelines. The study aimed to investigate the role of prophylactic anticoagulation with warfarin for 3-6 months in LVT recurrence and other clinical outcomes after LVT resection and left ventricular aneurysm (LVA) surgery. METHODS: All consecutive patients undergoing LVT resection together with LVA surgery in our institution between 2010.1.1 and 2021.4.1 were included in the study. Individuals included were divided into two groups based on whether warfarin was administered at discharge. Patients with warfarin were matched to their counterparts without warfarin based on the baseline characteristics via propensity score matching (PSM) at the ratio of 1:1. The primary outcome was LVT recurrence. The secondary outcomes were major adverse cardiac and cerebrovascular events (MACCEs) and the composite endpoint of LVT recurrence and MACCEs. RESULTS: After PSM, a total of 118 patients were included in the study, among whom 59 received warfarin therapy at discharge and 59 didn't. During the median follow-up of 56.5 months, 21 out of 118 patients had LVT recurrence and the recurrence rate was 17.8% There was no systemic embolism resulting from the recurrent LVT. Kaplan-Meir analysis showed no significant difference in LVT recurrence (p = .86), MACCEs (p = .48) and the composite endpoint of LVT recurrence, and MACCEs (p = .89). Cox proportional hazards regression model showed that history of PCI (hazard ratio [HR] 2.778, 95% confidence interval [CI] 1.087-7.100, p = .033) and LVA surgical strategy of linear suture (HR 8.768, 95% CI 1.139-67.517, p = .037) were independent risk factors of LVT recurrence. CONCLUSIONS: Prophylactic anticoagulation with warfarin for 3-6 months may be unnecessary with no benefit in terms of LVT recurrence and other clinical outcomes.

Long-Term Outcomes of Left Ventricular Restoration in Patients Ineligible for Concomitant Coronary Artery Bypass Grafting.

BACKGROUND: The prognosis of severe coronary artery disease (CAD) patients undergoing left ventricular restoration (LVR) and ineligible for concomitant coronary artery bypass grafting (CABG) is unclear. This study illustrates the clinical characteristics and the long-term survival of these patients in a retrospective cohort. METHODS: From January 1999 to March 2021, a total of 78 patients underwent surgical left ventricular restoration without concomitant CABG at our center. The primary endpoint was the major adverse cardiovascular and cerebrovascular events (MACCE). Kaplan-Meier analysis was performed to calculate survival, and compared by log-rank test, followed by multiple adjustments using Cox regression. RESULTS: The mean age was 55.3 ± 11.4 years. There were 76 (97.4%) true and 2 (2.6%) pseudo-aneurysms. Forty-six (59.0%) patients presented NYHA functional class III or IV. The mean EuroSCORE was 10.6 ± 3.2. Concomitant surgeries included mitral valve repair (N = 3), mitral valve replacement (N = 2), tricuspid valve repair (N = 2), ventricular septal defect closure (N = 18), maze procedure (N = 1), and appendage ligation (N = 1). Reoperation for bleeding was performed in one patient (1.3%). Prolonged ventilation was observed in 21 (26.9%) patients. Fourteen (17.9%) patients presented with low cardiac output and were supported with IABP. Operative death occurred in one (1.3%) patient. The median duration of echocardiographic follow-up was 53 months (interquartile range, 81.5) and was obtained in 46 (59.0%) patients. Left ventricular ejection fraction (LVEF) improved from 41.1% ± 10.5% to 45.6% ± 7.9% (P < 0.001), and the left ventricular end-diastolic dimension (LVEDD) fell from 57.8 ± 6.6 mm to 52.0 ± 6.2 mm (P < 0.001). The median patient follow-up time was 79.5 months (interquartile range, 53.5). Overall, 1-, 5-, and 10-year survival rates were 98.7%, 95.5% and 82.3%, respectively. CONCLUSIONS: Patients with severe CAD and ineligible for concomitant CABG are in critical condition, and LVR could be a reliable approach to improving cardiac function with satisfactory early and long-term outcomes.