A New Fingerprint and Graph Hybrid Neural Network for Predicting Molecular Properties.

Machine learning plays a role in accelerating drug discovery, and the design of effective machine learning models is crucial for accurately predicting molecular properties. Characterizing molecules typically involves the use of molecular fingerprints and molecular graphs. These are input into a multilayer perceptron (MLP) and variants of graph neural networks, such as graph attention networks (GATs). Due to the diverse types and large dimension of fingerprints, models may contain many features that are relatively irrelevant or redundant; meanwhile, although the GAT excels in handling heterogeneous graph tasks, it lacks the ability to extract collaborative information from neighboring nodes, which is crucial in scenarios where it cannot capture the joint influence of adjacent groups on atoms. To overcome these challenges, we introduce a hybrid model, combining improved GAT and MLP. In GAT, the recurrent neural network is employed to capture collaborative information. To address the dimensionality issue, we propose a feature selection algorithm, which is based on the principle of maximizing relevance while minimizing redundancy. Through experiments on 13 public data sets and 14 breast cell lines, our model demonstrates superior performance compared to state-of-the-art deep learning and traditional machine learning algorithms. Additionally, a series of ablation experiments were conducted to demonstrate the advantages of our improved version, as well as its antinoise capability and interpretability. These results indicate that our model holds promising prospects for practical applications.

Lipid remodelling and the conversion of lipids into sugars associated with tolerance to cadmium toxicity during white clover seed germination.

Cadmium (Cd) is a leading environmental issue worldwide. The current study was conducted to investigate Cd tolerance of 10 commercial white clover (Trifolium repens) cultivars during seed germination and to further explore differences in lipid remodelling, glycometabolism, and the conversion of lipids into sugars contributing to Cd tolerance in the early phase of seedling establishment as well as the accumulation of Cd in seedlings and mature plants. The results show that Cd stress significantly reduced seed germination of 10 cultivars. Compared to Cd-sensitive Sulky, Cd-tolerant Pixie accelerated amylolysis to produce more glucose, fructose, and sucrose by maintaining higher amylase and sucrase activities under Cd stress. Pixie maintained higher contents of various lipids, higher DGDG/MGDG ratio, and lower unsaturation levels of lipids, which could be beneficial to membrane stability and integrity as well as signal transduction in cells after being subjected to Cd stress. In addition, Pixie upregulated expression levels of key genes (TrACX1, TrACX4, TrSDP6, and TrPCK1) involved in the conversion of lipids into sugars for early seedling establishment under Cd stress. These findings indicate that lipid remodelling, enhanced glycometabolism, and accelerated conversion of lipids into sugars are important adaptive strategies for white clover seed germination and subsequent seedling establishment under Cd stress. In addition, Pixie not only accumulated more Cd in seedlings and mature plants than Sulky but also had significantly better growth and phytoremediation efficiency under Cd stress. Pixie could be used as a suitable and critical germplasm for the rehabilitation and re-establishment of Cd-contaminated areas.

Structures of Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus virions reveal species-specific tegument and envelope features.

Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) are classified into the gammaherpesvirus subfamily of Herpesviridae , which stands out from its alpha- and betaherpesvirus relatives due to the tumorigenicity of its members. Although structures of human alpha- and betaherpesviruses by cryogenic electron tomography (cryoET) have been reported, reconstructions of intact human gammaherpesvirus virions remain elusive. Here, we structurally characterize extracellular virions of EBV and KSHV by deep learning-enhanced cryoET, resolving both previously known monomorphic capsid structures and previously unknown pleomorphic features beyond the capsid. Through subtomogram averaging and subsequent tomogram-guided sub-particle reconstruction, we determined the orientation of KSHV nucleocapsids from mature virions with respect to the portal to provide spatial context for the tegument within the virion. Both EBV and KSHV have an eccentric capsid position and polarized distribution of tegument. Tegument species span from the capsid to the envelope and may serve as scaffolds for tegumentation and envelopment. The envelopes of EBV and KSHV are less densely populated with glycoproteins than those of herpes simplex virus 1 and human cytomegalovirus, representative members of alpha- and betaherpesviruses, respectively. This population density of glycoproteins correlates with their relative infectivity against HEK293T cells. Also, we observed fusion protein gB trimers exist within triplet arrangements in addition to standalone complexes, which is relevant to understanding dynamic processes such as fusion pore formation. Taken together, this study reveals nuanced yet important differences in the tegument and envelope architectures among human herpesviruses and provides insights into their varied cell tropism and infection. Importance: Discovered in 1964, Epstein-Barr virus (EBV) is the first identified human oncogenic virus and the founding member of the gammaherpesvirus subfamily. In 1994, another cancer-causing virus was discovered in lesions of AIDS patients and later named Kaposi's sarcoma-associated herpesvirus (KSHV), the second human gammaherpesvirus. Despite the historical importance of EBV and KSHV, technical difficulties with isolating large quantities of these viruses and the pleiomorphic nature of their envelope and tegument layers have limited structural characterization of their virions. In this study, we employed the latest technologies in cryogenic electron microscopy (cryoEM) and tomography (cryoET) supplemented with an artificial intelligence-powered data processing software package to reconstruct 3D structures of the EBV and KSHV virions. We uncovered unique properties of the envelope glycoproteins and tegument layers of both EBV and KSHV. Comparison of these features with their non-tumorigenic counterparts provides insights into their relevance during infection.

Associations between left-behind children's characteristics and psychological symptoms: a cross-sectional study from China.

BACKGROUND: Parent-child separation poses a significant challenge for left-behind children (LBC). However, limited empirical evidence exists regarding the correlation between left-behind characteristics and the psychological symptoms of LBC. This study investigated psychological symptoms among LBC and explored associations between left-behind characteristics and those symptoms. METHODS: Using stratified cluster sampling, 1,832 LBC aged 13-18 years from three cities in East China were selected for analysis. Participants' depression and anxiety symptoms were assessed with the Patient Health Questionnaire 9 and the General Anxiety Disorder 7, respectively. Chi-square tests were used to compare differences in detection rates of psychological symptoms among LBC in different groups. Binary logistic regression analysis was used to infer associations between left-behind characteristics and psychological symptoms. RESULTS: Depression and anxiety symptoms were detected in 32.86% and 33.24%, respectively, of participating LBC. Univariate analysis showed statistically significant differences in detection rates of depression symptoms by sex, grade, and timing of parent-child separation. Statistically significant differences were observed in anxiety symptom rates by sex, grade, type of caregiver, and timing of mother-child separation. Multivariate analysis indicated a positive association between LBC's anxiety symptoms and mother-child separation that occurred during post-primary school, and type of caregiver (father only or mother only). Our findings confirm a positive association between left-behind characteristics and anxiety symptoms among LBC. CONCLUSION: The timing of mother-child separation and type of caregiver are potential risk factors for the development of anxiety symptoms in this population.

An AIE-active tetra-aryl imidazole-derived chemodosimeter for turn-on recognition of hydrazine and its bioimaging in living cells.

A new chemodosimeter SWJT-31 with an aggregation-induced emission (AIE) effect was designed and constructed. Upon increasing the water fraction in the solution, it exhibited typical AIE, which showed bright red fluorescence at 610 nm. SWJT-31 could sensitively and specifically recognize hydrazine by the TICT effect with an LOD of 33.8 nM, which was much lower than the standard of the USEPA. A portable test strip prepared using SWJT-31 was also developed for the visual detection of hydrazine. Eventually, it was successfully used for the detection of hydrazine in water samples and HeLa cells.

A Bioinspired Photosensitizer Performs Tumor Thermoresistance Reversion to Optimize the Atraumatic Mild-Hyperthermia Photothermal Therapy for Breast Cancer.

Mild-hyperthermia photothermal therapy (mPTT) has therapeutic potential with minimized damage to normal tissues. However, the poorly vascularized tumor area severely hampers the penetration of photothermal agents (PTAs), resulting in their heterogeneous distribution and the subsequent heterogeneous local temperature during mPTT. The presence of regions below the therapeutic 42 °C threshold can lead to incomplete tumor ablation and potential recurrence. Additionally, tumor anti-apoptosis and cytoprotection pathways, particularly activated thermoresistance, can nullify mild hyperthermia-induced tumor damage. Therefore, a bioinspired photosensitizer decorated with leucine to form biomimetic nanoclusters (CP-PLeu nanoparticles (NPs)) aimed at achieving rapid and homogeneous accumulation in tumors, is introduced. Moreover, CP-PLeu exhibits photodynamic effects that reverse tumor thermoresistance and physiological repair mechanisms, thereby inhibiting tumor resistance to hyperthermia. With the addition of NIR-II laser irradiation, CP-PLeu optimizes the therapeutic efficacy of mPTT and contributes to a minimally invasive therapeutic process for breast cancer. This therapeutic strategy, utilizing a biomimetic photosensitizer for homogeneous distribution of therapeutic temperature and photoactivated reversal of tumor thermoresistance, successfully achieves efficient breast tumor inhibition through an atraumatic mPTT process.

Ocular surface in patients with different degrees of myopia.

AIM: To investigate the clinical features of the ocular surface in patients with different degrees of myopia. METHODS: A cross-sectional study was conducted involving 122 participants with myopia in Beijing Tongren Hospital from February to June, 2023. After completing the Ocular Surface Disease Index (OSDI) score scale, measurements were taken for refraction, biometric parameters and ocular surface parameters. The prevalence, severity and related parameters of the dry eye among different groups based on axial length (AL) were compared. Correlation analysis was performed between ocular surface parameters and refraction/biometric measurement parameters. RESULTS: Statistically significant differences were observed in refractive error, corneal thickness, anterior chamber depth, and subfoveal choroidal thickness among the groups (all P<0.05). With the increase in AL, the incidence and severity of dry eye increased significantly (P<0.05). Moreover, the tear film break-up time (BUT) shortened (P<0.05), and the corneal fluorescein staining (CFS) points increased significantly (P<0.05). OSDI scores were positively correlated with AL and spherical equivalent (SE; both P<0.05); BUT was negatively correlated with AL, SE, and corneal astigmatism (AST; all P<0.05); Schirmer I test (SIT) results were negatively correlated with AL and SE (both P<0.05). CONCLUSION: AL elongation is a risk factor for dry eye onset in myopic participants. The longer the AL, the more severe the dry eye is, with the increased CFS spots and tear film instability. Additionally, SE and AST exhibit negative correlations with dry eye symptom scores and ocular surface parameters.

Protective effect of honokiol on cadmium-induced liver injury in chickens.

Cadmium (Cd), a highly toxic heavy metal in the environment, poses a significant threat to livestock and poultry farming. Honokiol (HNK), a Chinese herbal extract with potent antioxidant activity, acts through oxidative damage and inflammation. Cd induces oxidative stress and causes liver damage in animals. However, whether HNK can alleviate Cd-induced liver injury in chickens and its mechanism remains unclear. In this study, the 48 chickens were randomly allocated into 4 groups, control group, Cd group (70 mg/kg Cd), HNK group (200 mg/kg HNK) and Cd + HNK group (70 mg/kg Cd+200 mg/kg HNK). Results showed that HNK improved the Cd induced reduction in chicken body weight, liver weight, and liver coefficient. HNK recovered the Cd induced liver damaged through increased serum liver biochemical indexes, impaired liver oxidase activity and the disordered the expression level of antioxidant genes. HNK alleviated Cd induced pathological and ultrastructure damage of liver tissue and liver cell that leads apoptosis. HNK decreased Cd contents in the liver, Cd induced disturbances in the levels of trace elements such as iron, copper, zinc, manganese, and selenium. HNK attenuated the damage to the gap junction structure of chicken liver cells caused by Cd and reduced the impairment of oxidase activity and the expression level of antioxidant genes induced by Cd. In conclusion, HNK presents essential preventive measures and a novel pharmacological potential therapy against Cd induced liver injury. Our experiments show that HNK can be used as a new green feed additive in the poultry industry, which provides a theoretical basis for HNK to deal with the pollution caused by Cd in the poultry industry.

Correction: Xia et al. Resveratrol Alleviates Zearalenone-Induced Intestinal Dysfunction in Mice through the NF-κB/Nrf2/HO-1 Signalling Pathway. Foods 2024, 13, 1217.

In the original publication [...].

Strategies for developing µ opioid receptor agonists with reduced adverse effects.

Opioids are currently the most effective and widely used painkillers in the world. Unfortunately, the clinical use of opioid analgesics is limited by serious adverse effects. Many researchers have been working on designing and optimizing structures in search of novel µ opioid receptor(MOR) agonists with improved analgesic activity and reduced incidence of adverse effects. There are many strategies to develop MOR drugs, mainly focusing on new low efficacy agonists (potentially G protein biased agonists), MOR agonists acting on different Gα subtype, targeting opioid receptors in the periphery, acting on multiple opioid receptor, and targeting allosteric sites of opioid receptors, and others. This review summarizes the design methods, clinical applications, and structure-activity relationships of small-molecule agonists for MOR based on these different design strategies, providing ideas for the development of safer novel opioid ligands with therapeutic potential.

Study on the mechanism of heterogeneous tumor-associated macrophages in three subtypes of breast cancer through the integration of single-cell RNA sequencing and in vitro experiments.

BACKGROUND: Tumor-associated macrophages (TAM) exert a significant influence on the progression and heterogeneity of various subtypes of breast cancer (BRCA). However, the roles of heterogeneous TAM within BRCA subtypes remain unclear. Therefore, this study sought to elucidate the role of TAM across the following three BRCA subtypes: triple-negative breast cancer, luminal, and HER2. MATERIALS AND METHODS: This investigation aimed to delineate the variations in marker genes, drug sensitivity, and cellular communication among TAM across the three BRCA subtypes. We identified specific ligand-receptor (L-R) pairs and downstream mechanisms regulated by VEGFA-VEGFR1, SPP1-CD44, and SPP1-ITGB1 L-R pairs. Experimental verification of these pairs was conducted by co-culturing macrophages with three subtypes of BRCA cells. RESULTS: Our findings reveal the heterogeneity of macrophages within the three BRCA subtypes, evidenced by variations in marker gene expression, composition, and functional characteristics. Notably, heterogeneous TAM were found to promote invasive migration and epithelial-mesenchymal transition (EMT) in MDA-MB-231, MCF-7, and SKBR3 cells, activating NF-κB pathway via P38 MAPK, TGF-ß1, and AKT, respectively, through distinct VEGFA-VEGFR1, SPP1-CD44, and SPP1-ITGB1 L-R pairs. Inhibition of these specific L-R pairs effectively reversed EMT, migration, and invasion of each cancer cells. Furthermore, we observed a correlation between ligand gene expression and TAM sensitivity to anticancer drugs, suggesting a potential strategy for optimizing personalized treatment guidance. CONCLUSION: Our study highlights the capacity of heterogeneous TAM to modulate biological functions via distinct pathways mediated by specific L-R pairs within diverse BRCA subtypes. This study might provide insights into precision immunotherapy of different subtypes of BRCA.

Identification of m6A modification patterns and RBM15 mediated macrophage phagocytosis in pancreatic cancer: An integrative analysis.

Pancreatic cancer (PC) responds weakly to conventional immunotherapy. RNA N6-methyladenosine (m6A) modification has an essential role in the immune response, while its potential role in PC tumor microenvironment (TME) immune cell infiltration remains unknown. In this study, we thoroughly assessed the m6A modification patterns of 472 PC samples using 19 m6A regulators, and we systematically correlated these modification patterns with TME immune cell infiltration characteristics. We also created the m6Ascore and evaluated the m6A modification patterns of individual tumors, identified three different m6A modification patterns, and explored the role of the important m6A "writer" RBM15 in the regulation of macrophage function in PC. Two independent PC cohorts confirmed that patients with higher m6Ascore showed significant survival benefit. We verified that knockdown of RBM15 has the ability to inhibit PC growth and to promote macrophage infiltration and enhance phagocytosis of PC cells by macrophages. In conclusion, m6A modifications play a non-negligible role in the formation of TME diversity and complexity in PC. We reveal that inhibition of RBM15 suppresses PC development and modulates macrophage phagocytosis, and provide a more effective immunotherapeutic strategy for PC.

Diagnostic efficiency of conventional ultrasound, shear wave elastography, and superb microvascular imaging in evaluating ulnar neuropathy at the elbow.

INTRODUCTION/AIMS: The current diagnosis of ulnar neuropathy at the elbow (UNE) relies mainly on the clinical presentation and nerve electrodiagnostic (EDX) testing, which can be uncomfortable and yield false negatives. The aim of this study was to investigate the diagnostic value of conventional ultrasound, shear wave elastography (SWE), and superb microvascular imaging (SMI) in diagnosing UNE. METHODS: We enrolled 40 patients (48 elbows) with UNE and 48 healthy volunteers (48 elbows). The patients were categorized as having mild, moderate or severe UNE based on the findings of EDX testing. The cross-sectional area (CSA) was measured using conventional ultrasound. Ulnar nerve (UN) shear wave velocity (SWV) and SMI were performed in a longitudinal plane. RESULTS: Based on the EDX findings, UNE severity was graded as mild in 4, moderate in 10, and severe in 34. The patient group showed increased ulnar nerve CSA and stiffness at the site of maximal enlargement (CSA mean at the site of max enlargement [CSAmax] and SWV mean at the site of max enlargement [SWVmax]), ulnar nerve CSA ratio, and stiffness ratio (elbow-to-upper arm), compared with the control group (p < .001). Furthermore, the severe UNE group showed higher ulnar nerve CSAmax and SWVmax compared with the mild and moderate UNE groups (p < .001). The cutoff values for diagnosis of UNE were 9.5 mm2 for CSAmax, 3.06 m/s for SWVmax, 2.00 for CSA ratio, 1.36 for stiffness ratio, and grade 1 for SMI. DISCUSSION: Our findings suggest that SWE and SMI are valuable diagnostic tools for the diagnosis and assessment of severity of UNE.

γ-Aminobutyric acid (GABA) priming alleviates acid-aluminum toxicity to roots of creeping bentgrass via enhancements in antioxidant defense and organic metabolites remodeling.

MAIN CONCLUSION: γ-Aminobutyric acid alleviates acid-aluminum toxicity to roots associated with enhanced antioxidant metabolism as well as accumulation and transportation of citric and malic acids. Aluminum (Al) toxicity has become the main limiting factor for crop growth and development in acidic soils and is further being aggravated worldwide due to continuous industrial pollution. The current study was designed to examine effects of GABA priming on alleviating acid-Al toxicity in terms of root growth, antioxidant defense, citrate and malate metabolisms, and extensive metabolites remodeling in roots under acidic conditions. Thirty-seven-day-old creeping bentgrass (Agrostis stolonifera) plants were used as test materials. Roots priming with or without 0.5 mM GABA for 3 days were cultivated in standard nutrient solution for 15 days as control or subjected to nutrient solution containing 5 mM AlCl3·6H2O for 15 days as acid-Al stress treatment. Roots were sampled for determinations of root characteristics, physiological and biochemical parameters, and metabolomics. GABA priming significantly alleviated acid-Al-induced root growth inhibition and oxidative damage, despite it promoted the accumulation of Al in roots. Analysis of metabolomics showed that GABA priming significantly increased accumulations of organic acids, amino acids, carbohydrates, and other metabolites in roots under acid-Al stress. In addition, GABA priming also significantly up-regulated key genes related to accumulation and transportation of malic and citric acids in roots under acid-Al stress. GABA-regulated metabolites participated in tricarboxylic acid cycle, GABA shunt, antioxidant defense system, and lipid metabolism, which played positive roles in reactive oxygen species scavenging, energy conversion, osmotic adjustment, and Al ion chelation in roots.

Regional Variability in Survival for Patients Diagnosed with Selected Central Nervous System Tumours in Canada.

Canada's decentralized healthcare system may lead to regional disparities in survival among Canadians diagnosed with central nervous system (CNS) tumours. We identified 50,670 patients diagnosed with a first-ever primary CNS tumour between 2008 and 2017 with follow-up until 31 December 2017. We selected the four highest incidence histologies and used proportional hazard regression to estimate hazard ratios (HRs) for five regions (British Columbia, Prairie Provinces, Ontario, Atlantic Provinces and the Territories), adjusting for sex, tumour behaviour and patient age. Ontario had the best survival profile for all histologies investigated. The Atlantic Provinces had the highest HR for glioblastoma (HR = 1.26, 95% CI: 1.18-1.35) and malignant glioma not otherwise specified (NOS) (Overall: HR = 1.87, 95% CI:1.43-2.43; Pediatric population: HR = 2.86, 95% CI: 1.28-6.39). For meningioma, the Territories had the highest HR (HR = 2.44, 95% CI: 1.09-5.45) followed by the Prairie Provinces (HR = 1.52, 95% CI: 1.38-1.67). For malignant unclassified tumours, the highest HRs were in British Columbia (HR = 1.45, 95% CI: 1.22-1.71) and the Atlantic Provinces (HR = 1.40, 95% CI: 1.13-1.74). There are regional differences in the survival of CNS patients at the population level for all four specific histological types of CNS tumours investigated. Factors contributing to these observed regional survival differences are unknown and warrant further investigation.

Performance evaluation of the effect of humic acid on Anammox granular sludge: Apparent morphology, nitrogen removal and microbial community.

Humic acid (HA) is a typical refractory organic matter, so it is of great significance to investigate its effect on the performance of Anammox granular sludge. When the dosage of HA ≤ 50 mg/L, HA promotes the total nitrogen removal rate (NRR) to 1.45 kg/(m3·day). When HA was between 50 and 100 mg/L, the NRR of Anammox was stable. At this time, the adsorption of HA causes the sludge to gradually turn from red to brown, but the activities of heme and enzymes showed that its capacity was not affected. When HA levels reached 250 mg/L, the NRR dropped to 0.11 kg/(m3·day). Moderate HA levels promoted the release of extracellular polymeric substance (EPS), but excessive HA levels lead to a decrease in EPS concentrations. HA inhibited Anammox activity, which indirectly hindered the transmission of substrate and accumulated substrate toxicity. Although HA promoted the increase of heterotrophic microbial abundance in Anammox system, the microbial diversity decreased gradually. With the increase of HA concentration, the abundance of Candidatus_Brocadia, the main functional microorganism of Anammox system, decreased gradually, while the abundance of Candidatus_Kuenenia increased gradually.

The impact of facial attractiveness and alleged personality traits on fairness decisions in the ultimatum game: Evidence from ERPs.

In the mind of the beholder the personality and facial attractiveness of others are interrelated. However, how these specific properties are processed in the neurocognitive system and interact with each other while economic decisions are made is not well understood. Here, we combined the ultimatum game with EEG technology, to investigate how alleged personality traits and the perceived facial attractiveness of proposers of fair and unfair offers influence their acceptance by the responders. As expected, acceptance rate was higher for fair than unfair allocations. Overall, responders were more likely to accept proposals from individuals with higher facial attractiveness and with more positive personality traits. In ERPs, words denoting negative personality traits elicited larger P2 components than positive trait words, and more attractive faces elicited larger LPC amplitudes. Replicating previous findings, FRN amplitudes were larger to unfair than to fair allocations. This effect was diminished if the proposer's faces were attractive or associated with positive personality traits. Hence, facial attractiveness and the valence of personality traits seem to be evaluated independently and at different time points. Subsequent decision making about unfair offers is similarly influenced by high attractiveness and positive personality of the proposer, diminishing the negative response normally elicited by "unfair" proposals, possibly due a "reward" effect. In the ERPs to the proposals the effect of positive personality and attractiveness were seen in the FRN and P300 components but for positive personality traits the effect even preceded the FRN effect. Altogether, the present results indicate that both high facial attractiveness and alleged positive personality mitigate the effects of unfair proposals, with temporally overlapping but independent neurocognitive correlates.

The Role of Inflammasome in Abdominal Aortic Aneurysm and Its Potential Drugs.

Abdominal aortic aneurysm (AAA) has been recognized as a serious chronic inflammatory degenerative aortic disease in recent years. At present, there is no other effective intervention except surgical treatment for AAA. With the aging of the human population, its incidence is increasing year by year, posing a serious threat to human health. Modern studies suggest that vascular chronic inflammatory response is the core process in AAA occurrence and development. Inflammasome, a multiprotein complex located in the cytoplasm, mediates the expression of various inflammatory cytokines like interleukin (IL)-1ß and IL-18, and thus plays a pivotal role in inflammation regulation. Therefore, inflammasome may exert a crucial influence on the progression of AAA. This article reviews some mechanism studies to investigate the role of inflammasome in AAA and then summarizes several potential drugs targeting inflammasome for the treatment of AAA, aiming to provide new ideas for the clinical prevention and treatment of AAA beyond surgical methods.

A premium for positive social interest and attractive voices in the acceptability of unfair offers? An ERP study.

Although the attractiveness of voices plays an important role in social interactions, it is unclear how voice attractiveness and social interest influence social decision-making. Here, we combined the ultimatum game with recording event-related brain potentials (ERPs) and examined the effect of attractive versus unattractive voices of the proposers, expressing positive versus negative social interest ("I like you" vs. "I don't like you"), on the acceptance of the proposal. Overall, fair offers were accepted at significantly higher rates than unfair offers, and high voice attractiveness increased acceptance rates for all proposals. In ERPs in response to the voices, their attractiveness and expressed social interests yielded early additive effects in the N1 component, followed by interactions in the subsequent P2, P3 and N400 components. More importantly, unfair offers elicited a larger Medial Frontal Negativity (MFN) than fair offers but only when the proposer's voice was unattractive or when the voice carried positive social interest. These results suggest that both voice attractiveness and social interest moderate social decision-making and there is a similar "beauty premium" for voices as for faces.