A survey of generative AI for de novo drug design: new frontiers in molecule and protein generation.

Artificial intelligence (AI)-driven methods can vastly improve the historically costly drug design process, with various generative models already in widespread use. Generative models for de novo drug design, in particular, focus on the creation of novel biological compounds entirely from scratch, representing a promising future direction. Rapid development in the field, combined with the inherent complexity of the drug design process, creates a difficult landscape for new researchers to enter. In this survey, we organize de novo drug design into two overarching themes: small molecule and protein generation. Within each theme, we identify a variety of subtasks and applications, highlighting important datasets, benchmarks, and model architectures and comparing the performance of top models. We take a broad approach to AI-driven drug design, allowing for both micro-level comparisons of various methods within each subtask and macro-level observations across different fields. We discuss parallel challenges and approaches between the two applications and highlight future directions for AI-driven de novo drug design as a whole. An organized repository of all covered sources is available at https://github.com/gersteinlab/GenAI4Drug.

Single and mixture toxicity of cadmium and copper to swim bladder in early life stages of Japanese medaka (Oryzias latipes).

Toxicity observed in aquatic ecosystems often cannot be explained by the action of a single pollutant. Likewise, evaluation standards formulated by a single effect cannot truly reflect the environmental quality requirements. The study of mixtures is needed to provide environmental relevance and knowledge of combined toxicity. In this study, the embryos of Japanese medaka (Oryzias latipes) were treated with individual and binary mixture of copper (Cu) and cadmium (Cd) until 12 days post-fertilization (dpf). Hatching, mortality, development, histology and gene expression were assessed. Our results showed that the highest concentration mixture of Cd (10 mg/L) and Cu (1 mg/L) affected survival, hatching time and hatching success. Occurrence of uninflated swim bladder was the highest (value) with exposure to 10 mg/L Cd. Swim bladder was commonly over-inflated in a mixture (0.1 mg/L Cd + 1.0 mg/L Cu) exposure. Individuals exposed to the mixture (0.1 Cd + 1.0 Cu mg/L) showed up to a 7.69% increase in swim bladder area compared to the control group. The mixtures containing 0.1 or 10 mg/L Cd, each with 1.0 mg/L Cu resulted in significantly increased of Pbx1b expression, higher than any Cd or Cu alone (p < 0.01). In the co-exposure group (0.1/10 Cd + 1.0 Cu mg/L), Pbx1b expression was found at 12 dpf but not 7 dpf in controls. Higher concentrations of Cd may progressively reduce Pbx1b expression, potentially explaining why 75% of individuals in the 10 mg/L Cd group failed to inflate their swim bladders. Additionally, the swim bladder proved to be a valuable bio-indicator for biological evaluation.

Effects of cadmium and copper mixtures on antibiotic resistance genes in rhizosphere soil.

The evolvement and development of antibiotic resistance in microorganisms may be influenced by metals; however, it is still unclear how cadmium (Cd) and copper (Cu) combined affect the distribution and presence of antibiotic-resistance genes (ARGs) in rhizosphere soil. The aims of this research were to (1) compare the distribution patterns of bacterial communities and ARGs in response to the effects of Cd and Cu both separately and combined; (2) explore the possible mechanisms underlying the variation in soil bacterial communities and ARGs in addition to the combined effects of Cd, Cu, and various environmental variables (nutrients, pH, etc.); and (3) provide a reference for assessing the risks of metals (Cd and Cu) and ARGs. The findings showed that the multidrug resistance genes acrA and acrB and the transposon gene intI-1 were present in high relative abundance in bacterial communities. Cadmium and Cu had a substantial interaction effect on the abundance of acrA, whereas Cu had a notable main effect on the abundance of intI-1. According to the network analysis, the strong links between bacterial taxa and specific ARGs revealed that most ARGs were hosted by Proteobacteria, Actinobacteria, and Bacteroidetes. According to structural equation modeling, Cd had a larger effect on ARGs than Cu. Compared to previous analyses of ARGs, bacterial community diversity had little effect on ARGs in this study. Overall, the results may have important consequences for determining the possible hazard of soil metals and extend the understanding of how Cd and Cu co-select ARGs in rhizosphere soils.

Exposure estimates of parabens from personal care products compared with biomonitoring data in human hair from Northeast China.

Parabens (PBs), a class of endocrine-disrupting chemicals (EDCs), are extensively used as additives in personal care products (PCPs); however, distinguishing between endogenous and exogenous contamination from PCPs in hair remains a challenge. We conducted a comprehensive analysis of the levels, distribution patterns, impact factors, and sources of PBs in 119 human hair samples collected from Changchun, northeast China. The detection rates of methylparaben (MeP), propylparaben (PrP), and ethylparaben (EtP) in hair samples were found to be 100%. The concentration of PBs in hair followed the order of MeP (57.48 ng/g) > PrP (46.40 ng/g) > EtP (6.80 ng/g). The concentration of PrP in female hair was significantly higher (65.38 ng/g) than that observed in male hair (7.82 ng/g) (p < 0.05). The levels of excretion rates of MeP (ERMeP) and excretion rates of PrP (ERPrP) in the hair-dying samples (ERMeP: 17.89 ng/day; ERPrP: 14.15 ng/day) were found to be 2.52 and 2.40 times higher, respectively, compared to the non-hair-dying samples (ERMeP: 7.09 ng/day; ERPrP: 6.05 ng/day). However, the system exposure dosage (SED) results revealed that although hair dyes exhibited higher PBs, human exposure was found to be lower than certain PCPs. The results of the correlation analysis revealed that toner, face cream, body lotion, and hair conditioner were identified as the primary sources of PBs in male hair. Furthermore, the human exposure resulting from the utilization of female hair dye and serum exhibited a positive correlation with hair ERMeP and ERPrP levels, indicating in the screening of samples, excluding hair samples using hair dye and haircare essential oil can effectively avoid the interference caused by exogenous contamination from PCPs.

Characteristics and health risks of population exposure to phthalates via the use of face towels.

The production of face towels is growing at an annual rate of about 4% in China, reaching 1.13 million tons by 2021. Phthalates (PAEs) are widely used in textiles, and face towels, as an important household textile, may expose people to PAEs via the skin, further leading to health risks. We collected new face towels and analyzed the distribution characterization of PAEs in them. The changes of PAEs were explored in a face towel use experiment and a simulated laundry experiment. Based on the use of face towels by 24 volunteers, we calculated the estimated daily intake (EDI) and comprehensively assessed the hazard quotient (HQ), hazard index (HI), and dermal cancer risk (DCR) of PAEs exposure in the population. PAEs were present in new face towels at total concentrations of

KG4SL: knowledge graph neural network for synthetic lethality prediction in human cancers.

MOTIVATION: Synthetic lethality (SL) is a promising gold mine for the discovery of anti-cancer drug targets. Wet-lab screening of SL pairs is afflicted with high cost, batch-effect, and off-target problems. Current computational methods for SL prediction include gene knock-out simulation, knowledge-based data mining and machine learning methods. Most of the existing methods tend to assume that SL pairs are independent of each other, without taking into account the shared biological mechanisms underlying the SL pairs. Although several methods have incorporated genomic and proteomic data to aid SL prediction, these methods involve manual feature engineering that heavily relies on domain knowledge. RESULTS: Here, we propose a novel graph neural network (GNN)-based model, named KG4SL, by incorporating knowledge graph (KG) message-passing into SL prediction. The KG was constructed using 11 kinds of entities including genes, compounds, diseases, biological processes and 24 kinds of relationships that could be pertinent to SL. The integration of KG can help harness the independence issue and circumvent manual feature engineering by conducting message-passing on the KG. Our model outperformed all the state-of-the-art baselines in area under the curve, area under precision-recall curve and F1. Extensive experiments, including the comparison of our model with an unsupervised TransE model, a vanilla graph convolutional network model, and their combination, demonstrated the significant impact of incorporating KG into GNN for SL prediction. AVAILABILITY AND IMPLEMENTATION: : KG4SL is freely available at https://github.com/JieZheng-ShanghaiTech/KG4SL. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Potential health risks of metals in skin care products used by Chinese consumers aged 19-29 years.

Metal contamination of skin care products that occurs during their production poses potential health risks, which are of increasing concern, to consumers. Here, we collected 570 responses to an online survey to analyze the usage pattern of skin care products across China. Then a total of 30 commonly used skin care products with various prices and applications were purchased. The concentrations of metals (Al, Zn, Cu, Ni, Cr, Pb, Hg, and Cd) and metalloid As, were determined. Next, we improved the frequency calculation method and used the weighted exposure frequency to calculate the dermal absorption dose (DAD). The amounts of Zn, Cr, and Al that were assimilated by the human body via uptake were approximately 2 orders of magnitude greater than those of Pb, Hg, Cd, Ni and metalloid As. In addition, younger consumers were at higher risk of metals exposure than older consumers because of their higher frequency of use of skin care products. Al and Zn posed higher risk to consumers because of its high DAD. There was no significant chronic non-carcinogenic health risk (hazard index < 1) posed by skincare product use.

Metallic elements in human hair from residents in smelting districts in northeast China: Environmental factors and differences in ingestion media.

The health of residents in Huludao City is affected by the emissions of heavy metals from smelting, diet and atmospheric precipitation. This study investigated the concentrations of Hg, Cd, Pb, Cu and Zn in scalp hair samples from 259 residents of different ages and genders from five districts in Huludao City and examined the main factors for heavy metal exposure. Cd and Pb concentrations in hair samples exceeded the normal concentration ranges for human hair (Cd < 0.3 mg/kg; Pb < 9.3 mg/kg), and the highest Pb concentrations were found in subjects in the age range 0-15 years. Samples from men were higher in Cd and Pb compared to those for women. Workers from the Huludao zinc plant (HZP) had higher concentrations of all metals in their hair relative to other occupations except for Cu. Geographically, the highest Cd and Pb concentrations in hair were found for residents living in Daochi district (DCD) and the Zn plant district (ZPD), respectively. In smelting regions, the effects of dust ingestion on heavy metal exposure were more important than in non-smelting regions.

Effect of soil pH and organic matter content on heavy metals availability in maize (Zea mays L.) rhizospheric soil of non-ferrous metals smelting area.

Maize plant tissues and rhizosphere soil were collected from an agricultural area around the Huludao Zinc Plant in Liaoning Province, China, to investigate the effects of soil pH and organic matter content on heavy metal concentration and accumulation in different types of maize tissues. The mean pH of the soil samples was 7.02 (range 5.74-7.86), and the mean organic matter content was 31.03 g kg-1 (range 18.80-52.20 g kg-1). The average Cu, Zn, Pb, and Cd contents in soil were 2.92, 6.72, 7.95, and 16.28 times greater than the corresponding background values, respectively. The geo-accumulation index indicated that the soils were uncontaminated to moderately contaminated by Cu, moderately to strongly contaminated by Pb and Zn, and strongly contaminated by Cd. The average available Cu, Pb, Zn, and Cd contents in the soil samples were 16.34, 6.997, 69.77, and 0.190 mg kg-1, respectively, while their bioavailability coefficients were 28.53%, 1.65%, 40.44%, and 10.83%, respectively. The respective mean Pb and Cd concentrations in grain samples were 0.341 and 0.342 mg kg-1, which exceeded the maximum concentrations permitted by the Chinese National Standard. Thus, the maize grain is not safe for consumption and poses potential risks to human health. With the exception of Cu, the combined effect of pH and organic matter content had a stronger influence on the availability of heavy metals in soil compared with either factor alone. Cd uptake in maize plant tissues was affected by the combination of soil pH, organic matter content, and bioavailable Cd content in soil; however, the combination of these three factors had only slight effects on Cu, Zn, and Pb absorption in maize tissues.

The Toxicological Effects of Mercury Exposure in Marine Fish.

Since the Minamata incident in Japan, the public have become increasingly aware of the negative health effects caused by mercury pollution in the ocean. Consequently, there has been significant interest in the health of humans eating fish exposed to mercury (Hg). However, the toxicity of mercury to the marine fish themselves has received far less attention. In this review, we summarize mercury accumulation in marine fish and the toxicological effects of mercury exposure. Results showed that the bioaccumulation of mercury in marine fish was highly variable, and its concentration was affected by the specific physiological and ecological characteristics of different fish species. Mercury exposure can produce teratogenic, neurotoxic effects, and reproductive toxicity. These effects can then cause harm to cells, tissues, proteins and genes, and ultimately, the survival, growth, and behavior of marine fish. Future studies should afford more attention to the toxicological effect of mercury exposure upon marine fish.

Catadioptric planar compound eye with large field of view.

The planar compound eye has the advantages of simple structure and no requirement for complex relay optical elements, but the field of view (FOV) is very difficult to expand. Overcoming the limitation of FOV, especially with simple structures, is a great challenge for the development of planar compound eyes. Different from the existing designs that only considering refraction, this article proposes a catadioptric planar compound eye based on the reflection and refraction to expand the FOV. In the proposed design, the incident light from a large angle is reflected into the lenslet array by two rotationally symmetric mirrors whose surface equations are optimized by mathematical and optical softwares. The FOV of the proposed catadioptric planar compound eye theoretically can reach 96.6°, which is much wider than the opening record of 70°. Moreover, no distortion of the imaging system can be obtained theoretically in this design. Simulation results show a linearity of better than 99% for the most of the incident angles. The verification experiments show that the FOV of the proposed device can reach 90.7° while the FOV of the corresponding planar compound eye without mirrors is 41.6°. The proposed catadioptric planar compound eye has the great potential in monitoring, detection and virtual reality since the FOV has been widen significantly.

Catalytic pyrolysis of liquor-industry waste: Product and mechanism analysis.

The effects of three catalysts, namely Ni/γ-Al2O3, Fe/γ-Al2O3, and Mg/γ-Al2O3, on the three-phase products of liquor-industry waste pyrolysis were investigated in this study. Results indicated that the catalytic performance of Ni/γ-Al2O3 outperformed those of Fe/γ-Al2O3 and Mg/γ-Al2O3 significantly. The application of Ni/γ-Al2O3 facilitated the reformation of pyrolysis volatiles, leading to increased yields of H2 (174.1 mL/g), CH4 (80.7 mL/g), and CO (88.2 mL/g) by 980.00 %, 133.24 %, and 83.37 %, respectively. compared to catalyst-free conditions. The Ni/γ-Al2O3 also increased the low-level calorific value of biogas by 109.3 % compared to that under non-catalyst conditions. Moreover, Ni/γ-Al2O3 enhanced the relative concentrations of hydrocarbons in tar by 23.15 % while reducing the relative concentrations of O-species by 15.73 % compared to catalyst-free conditions through induced deoxygenation, decarboxylation, decarbonylation reactions as well as efficient steam reforming processes for tar and syngas upgrading purposes. Thus, incorporating Ni/γ-Al2O3 into the pyrolysis process represents a renewable approach for waste-to-energy conversion.

Multi-source exposure and health risks of phthalates among university students in Northeastern China.

The endocrine disruptor phthalates (PAEs) are widely used as important chemical additives in a variety of areas around the globe. PAEs are toxic to reproduction and development and may adversely affect the health of adolescents. Risk assessments of exposure to PAEs from different sources are more reflective of actual exposure than single-source assessments. We used personal exposure parameters to estimate the dose of PAEs to 107 university students from six media (including dormitory dust, dormitory air, clothing, food, disposable food containers, and personal care products (PCPs)) and three exposure routes (including ingestion, inhalation, and dermal absorption). Individual factors and lifestyles may affect PAE exposure to varying degrees. Based on a positive matrix factorization (PMF) model, the results indicated that the main sources of PAEs in dust were indoor building materials and plastics, while PCPs and adhesives were the major sources of airborne PAEs. The relative contribution of each source to PAE exposure showed that food and air were the primary sources of dimethyl phthalate (DMP) and dibutyl phthalate (DBP). Air source contributed the most to diethyl phthalate (DEP) exposure, followed by PCPs. Food was the most significant source of diisobutyl phthalate (DiBP), benzyl butyl phthalate (BBP), and bis(2-ethylhexyl) phthalate (DEHP) exposure. Additionally, the exposure of DEHP to dust was not negligible. The ingestion pathway was the most dominant among the three exposure pathways, followed by dermal absorption. The non-carcinogenic risk of PAEs from the six sources was within acceptable limits. DEHP exhibits a low carcinogenic risk. We suggest university students maintain good hygienic and living habits to minimize exposure to PAEs.

Single-cell genomics and regulatory networks for 388 human brains.

Single-cell genomics is a powerful tool for studying heterogeneous tissues such as the brain. Yet, little is understood about how genetic variants influence cell-level gene expression. Addressing this, we uniformly processed single-nuclei, multi-omics datasets into a resource comprising >2.8M nuclei from the prefrontal cortex across 388 individuals. For 28 cell types, we assessed population-level variation in expression and chromatin across gene families and drug targets. We identified >550K cell-type-specific regulatory elements and >1.4M single-cell expression-quantitative-trait loci, which we used to build cell-type regulatory and cell-to-cell communication networks. These networks manifest cellular changes in aging and neuropsychiatric disorders. We further constructed an integrative model accurately imputing single-cell expression and simulating perturbations; the model prioritized ~250 disease-risk genes and drug targets with associated cell types.

Single-cell genomics and regulatory networks for 388 human brains.

Single-cell genomics is a powerful tool for studying heterogeneous tissues such as the brain. Yet little is understood about how genetic variants influence cell-level gene expression. Addressing this, we uniformly processed single-nuclei, multiomics datasets into a resource comprising >2.8 million nuclei from the prefrontal cortex across 388 individuals. For 28 cell types, we assessed population-level variation in expression and chromatin across gene families and drug targets. We identified >550,000 cell type-specific regulatory elements and >1.4 million single-cell expression quantitative trait loci, which we used to build cell-type regulatory and cell-to-cell communication networks. These networks manifest cellular changes in aging and neuropsychiatric disorders. We further constructed an integrative model accurately imputing single-cell expression and simulating perturbations; the model prioritized ~250 disease-risk genes and drug targets with associated cell types.

Exposure of childbearing-aged female to phthalates through the use of personal care products in China: An assessment of absorption via dermal and its risk characterization.

Phthalates (PAEs) are widely used in personal care products (PCPs) and skin care packaging materials. Through national representative sampling, 328 childbearing-aged females in China were investigated by questionnaire, whose contact factors for 30 cosmetic products were collected. According to the daily exposure method and adverse cumulative effects of PAE exposure on female reproduction, we derived the ERα, ERß binding, and AR anti-androgenic effects. The utilization rates of acne cleanser, acne cream, cleanser (non-acne), and cream (non-acne) in volunteers were 21.90%, 22.22%, 51.63%, and 51.96%, respectively. Examining the data for PAEs in PCPs, the content of DBP (dibutyl phthalate) in them was significantly higher for tubes (0.26 ± 0.05 µg/g) and other packaging (pump type and metal tube) (0.25 ± 0.03 µg/g) than bowl (0.17 ± 0.04 µg/g). The DBP content of acne cream (0.27 ± 0.03 µg/g) was significantly higher than that of non-acne cream (0.17 ± 0.03 µg/g); likewise, there was significantly more DEHP (di (2-ethylhexyl) phthalate) in acne cleanser (0.87 ± 0.15 µg/g) than non-acne cleanser (0.64 ± 0.36 µg/g). Students and office worker were the main consumers of PCPs; however, among all occupation groups, the daily exposure dose of PCPs for workers was highest (mean = 0.0004, 0.0002, 0.0009 µg/kg bw/day for DEP (diethyl phthalate), DBP, and DEHP, respectively). The cumulative indices of PAEs' exposure revealed that the level of ERα and ERß binding and AR anti-androgenic effects in workers was respectively 0.4935, 0.0186, and 0.2411 µg/kg bw/day. The risk index (HITDI and HIRfDs) of DEP, DBP, and DEHP was lower than their corresponding reference value (hazard index <1), but using PCPs may cause potential health risks. Therefore, we should pay attention to the adverse effects of PAEs on female reproductive functioning, especially the cumulative exposure of females of childbearing age.

Rapid biodegradation of atrazine by a novel Paenarthrobacter ureafaciens ZY and its effects on soil native microbial community dynamic.

An atrazine-utilizing bacterium, designated as ZY, was isolated from agricultural soil and identified as Paenarthrobacter ureafaciens. The P. ureafaciens ZY demonstrated a significant degradation capacity of atrazine, with the degradation efficiency of 12.5 mg L-1 h-1 in liquid media (at pH 7, 30°C, and the atrazine level of 100 mg L-1). The P. ureafaciens ZY contained three atrazine-degrading genes (i.e., trzN, atzB, and atzC) could metabolize atrazine to form cyanuric acid, which showed lower biotoxicity than the parent atrazine as predicted by Ecological Structure Activity Relationships model. A laboratory-scale pot experiment was performed to examine the degradation of atrazine by P. ureafaciens ZY inoculation and investigate its effects on the native microbial communities. The results exhibited that the P. ureafaciens ZY was conductive to the degradation of atrazine, increased the total soil phospholipid fatty acids at the atrazine level of 50, 70, and 100 mg kg-1. By using high-throughput sequencing analysis, Frateuria, Dyella, Burkholderia-Caballeronia-Paraburkholderia were considered as the most important indigenous atrazine-degrading microorganisms due to their relative abundances were positively correlated with the atrazine degradation rate. In addition, P. ureafaciens ZY also increased the abundance of atrazine-degrading genus Streptomyces and Bacillus, indicating that there may be a synergic relationship between them in the process of atrazine degradation. Our work provides a new insight between inoculums and native microorganisms on the degradation of atrazine.

Inhalation Bioaccessibility and Risk Assessment of Metals in PM2.5 Based on a Multiple-Path Particle Dosimetry Model in the Smelting District of Northeast China.

PM2.5 can deposit and partially dissolve in the pulmonary region. In order to be consistent with the reality of the pulmonary region and avoid overestimating the inhalation human health risk, the bioaccessibility of PM2.5 heavy metals and the deposition fraction (DF) urgently needs to be considered. This paper simulates the bioaccessibility of PM2.5 heavy metals in acidic intracellular and neutral extracellular deposition environments by simulating lung fluid. The multipath particle dosimetry model was used to simulate DF of PM2.5. According to the exposure assessment method of the U.S. Environmental Protection Agency, the inhalation exposure dose threshold was calculated, and the human health risk with different inhalation exposure doses was compared. The bioaccessibility of heavy metals is 12.1−36.2%. The total DF of PM2.5 in adults was higher than that in children, and children were higher than adults in the pulmonary region, and gradually decreased with age. The inhalation exposure dose threshold is 0.04−14.2 mg·kg−1·day−1 for the non-carcinogenic exposure dose and 0.007−0.043 mg·kg−1·day−1 for the carcinogenic exposure dose. Cd and Pb in PM2.5 in the study area have a non-carcinogenic risk to human health (hazard index < 1), and Cd has no or a potential carcinogenic risk to human health. A revised inhalation health risk assessment may avoid overestimation.

Exposure of street sweepers to cadmium, lead, and arsenic in dust based on variable exposure duration in zinc smelting district, Northeast China.

Street dust is an important contributor to heavy metal exposure in street sweepers. In this work, the levels of cadmium (Cd), lead (Pb), and arsenic (As) in street dust were evaluated, and the corresponding health implications for street sweepers in the smelting district of Huludao city northeast China were assessed. The contributions of dietary sources and dust to total metal exposure in street sweepers were compared. Because street sweepers are exposed to street dust both during work and nonwork hours, the health risks faced by street sweepers are uncertain. Therefore, variable exposure duration was considered using a deterministic model. A probabilistic risk assessment model was developed to explore the health effects of street dust on street sweepers via Monte Carlo simulation. The various exposure parameters that affect risk were analyzed using sensitivity analysis. The average Cd, Pb, and As levels in the hair of street sweepers were 2.04, 20.12, and 0.52 mg·kg-1, respectively. These values were higher than those for residents (i.e., not street sweepers) of Huludao. Strong correlations were found between the logarithms (base 10) of the Cd, Pb, and As contents in dust and hair (rCd = 0.581, p < 0.01; rPb = 0.428, p < 0.01; rAs = 0.378, p < 0.01; n = 62). Based on analysis using deterministic models, the maximum exposures to Cd and Pb via dust through the alimentary canal were nearly three and six times higher than the dietary exposures, respectively. Sensitivity analysis indicated that exposure duration is an important parameter.

Effect of ciliary neurotrophic factor on neural differentiation of stem cells of human exfoliated deciduous teeth.

The stem cells of human exfoliated deciduous teeth (SHEDs) are considered to be one of the main sources of seed cells in stem cell therapy. The aim of this study was to examine the effect of ciliary neurotrophic factor (CNTF) on neurogenic differentiation of SHEDs. With the consent of parents, SHEDs from 6 to 8 year old children were isolated and cultured. The mesenchymal stemness and the potential of multidirectional (adipogenic and osteogenic) differentiation for the isolated SHEDs were firstly determined. The effect of CNTF on specific neurogenic differentiation of SHEDs was then examined by detecting the expression of marker genes and proteins via RT-PCR, immunoblotting, and immunofluorescence microscopy. The isolated SHEDs expressed specific surface markers of mesenchymal stem cells, and their potential of osteogenic and adipogenic differentiation were confirmed. CNTF promoted the differentiation of SHEDs into neuron-like cells with a high expression of acetylcholine transferase (CHAT), a marker of cholinergic neurons. The expression of other neuron markers including nestin, microtubule-associated protein 2 (MAP 2), and ß-tublin III was also detected. Interestingly, the expression of neurogenic markers was maintained at a high level after neurogenic induction. SHEDs can be induced by CNTF to differentiate into cholinergic neuron-like cells under appropriate culture conditions. Our findings have laid a foundation for future use of SHEDs to treat neurological diseases.