The marine-derived compound TAG alleviates Parkinson's disease by restoring RUBCN-mediated lipid metabolism homeostasis.

Parkinson's disease (PD) is the second most common neurodegenerative disease, and its prevalence is increasing. Currently, no effective therapies for PD exist. Marine-derived natural compounds are considered important resources for the discovery of new drugs due to their distinctive structures and diverse activities. In this study, tetrahydroauroglaucin (TAG), a polyketide isolated from a marine sponge, was found to have notable neuroprotective effects on MPTP/MPP+-induced neurotoxicity. RNA sequencing analysis and metabolomics revealed that TAG significantly improved lipid metabolism disorder in PD models. Further investigation indicated that TAG markedly decreased the accumulation of lipid droplets (LDs), downregulated the expression of RUBCN, and promoted autophagic flux. Moreover, conditional knockdown of Rubcn notably attenuated PD-like symptoms and the accumulation of LDs, accompanied by blockade of the neuroprotective effect of TAG. Collectively, our results first indicated that TAG, a promising PD therapeutic candidate, could suppress the accumulation of LDs through the RUBCN-autophagy pathway, which highlighted a novel and effective strategy for PD treatment.

Multimodal-Responsive Circularly Polarized Luminescence Security Materials.

Nations, industries, and aspects of everyday life have undergone forgery and counterfeiting ever since the emergence of commercialization. Securing documents and products with anticounterfeit additives shows promise for authentication, allowing one to combat ever-increasing global counterfeiting. One most-used effective encryption strategy is to combine with optical-security markers on the required protection objects; however, state-of-the-art labels still suffer from imitation due to their poor complexity and easy forecasting, as a result of deterministic production. Developing advanced anticounterfeiting tags with unusual optical characters and further incorporating complex security features are desired to achieve multimodal, unbreakable authentication capacity; unfortunately, this has not yet been achieved. Here, we prepare a series of stable circularly polarized luminescence (CPL) materials, composed of toxicity-free, high-quality-emitting inorganic quantum dots (QDs) and liquid crystals, using a designed helical-coassembly strategy. This CPL system achieves a figure of merit (FM, assessing the performance of both luminescence dissymmetry and quantum yield) value of 0.39, fulfilling practical demands for anticounterfeiting applications. Based on these CPL structures, we produce a type of multimodal-responsive security materials (MRSMs) that exhibits six different stimuli-responsive modes, including light activation, polarization, temperature, voltage, pressure, and view angle. Thus, we show a proof-of-principle blockchain-like integrated anticounterfeiting system, allowing multimodal-responsive, interactive/changeable information encryption-decryption. We further encapsulate the obtained security materials into a fiber to expand our materials to work on flexible fabrics, that is, building an intelligent textile with a color-adaptable function along with environmental change.

Involvement of transverse mesocolon is associated with development of colonic fistula in patients with acute necrotizing pancreatitis.

BACKGROUND: Involvement of transverse mesocolon (TM) during acute necrotizing pancreatitis(ANP) indicates that inflammation has spread from retroperitoneal space to peritoneum. Nevertheless, the impact of TM involvement, as confirmed by contrast-enhanced computed tomography (CECT), on local complications and clinical outcomes was poorly investigated. PURPOSE: This study aimed to explore the association between CECT-diagnosed TM involvement and the development of colonic fistula in a cohort of ANP patients. METHODS: This is a single-center, retrospective cohort study involving ANP patients admitted from January 2020 to December 2020. TM involvement was diagnosed by two experienced radiologists. The study subjects were enrolled consecutively and divided into two groups: TM involvement and non-TM involvement. The primary outcome was colonic fistula during the index admission. Clinical outcomes were compared between the two groups, and the association between the TM involvement and the development of colonic fistula was assessed using multivariable analysis to adjust for baseline unbalances. RESULTS: A total of 180 patients with ANP were enrolled, and 86 (47.8%) patients had TM involvement. The incidence of the colonic fistula is significantly higher in patients with TM involvement (16.3% vs. 5.3%;p = 0.017). Moreover, the length of hospital stay was 24(13,68) days in patients with TM involvement and 15(7,31) days in those not (p = 0.001). Analysis of multivariable logistic regression revealed that TM involvement is an independent risk factor for the development of colonic fistula (odds ratio: 10.253, 95% CI: 2.206-47.650, p = 0.003). CONCLUSION: TM involvement in ANP patients is associated with development of colonic fistula in ANP patients.

Dilepton Rapidity Distribution in Drell-Yan Production to Third Order in QCD.

We compute for the first time the lepton-pair rapidity distribution in the photon-mediated Drell-Yan process to next-to-next-to-next-to-leading order in QCD. The calculation is based on the q_{T}-subtraction method, suitably extended to this order for quark-antiquark initiated Born processes. Our results display sizeable QCD corrections at next-to-next-to-next-to-leading order over the full rapidity region and provide a fully independent confirmation of the recent results for the total Drell-Yan cross section at this order.

Research progress on icariin, a traditional Chinese medicine extract, in the treatment of asthma.

Bronchial asthma is a common chronic airway disease, and long-term management of asthma is the focus and challenge of clinical treatment. Glucocorticoids are often used as the first choice for the treatment of asthma. However, the occurrence of hormone dependence, hormone resistance, and local and systemic adverse reactions caused by hormone application also creates problems for the treatment of asthma. Finding new, safe, and effective therapeutic drugs is an important research direction at present. Icariin is an effective ingredient of the traditional Chinese medicine, Epimedium. It has various biological attributes such as anti-inflammatory and antioxidative activities, and immune regulation. It has high safety and a wide range of clinical applications. Icariin has the characteristics of multitargeted intervention in the treatment of asthma. Here, we review the specific mechanisms of icariin in treating asthma, and icariin is considered a novel therapy in controlling asthma; however, the mechanism is still worth further investigation.

Early versus delayed intervention in necrotizing acute pancreatitis complicated by persistent organ failure.

BACKGROUND: Current guidelines for the treatment of patients with necrotizing acute pancreatitis (NAP) recommend that invasive intervention for pancreatic necrosis should be deferred to 4 or more weeks from disease onset to allow necrotic collections becoming "walled-off". However, for patients showing signs of clinical deterioration, especially those with persistent organ failure (POF), it is controversial whether this delayed approach should always be adopted. In this study, we aimed to assess the impact of differently timed intervention on clinical outcomes in a group of NAP patients complicated by POF. METHODS: All NAP patients admitted to our hospital from January 2013 to December 2017 were screened for potential inclusion. They were divided into two groups based on the timing of initial intervention (within 4 weeks and beyond 4 weeks). All the data were extracted from a prospectively collected database. RESULTS: Overall, 131 patients were included for analysis. Among them, 100 (76.3%) patients were intervened within 4 weeks and 31 (23.7%) underwent delayed interventions. As for organ failure prior to intervention, the incidences of respiratory failure, renal failure and cardiovascular failure were not significantly different between the two groups (P > 0.05). The mortality was not significantly different between the two groups (35.0% vs. 32.3%, P = 0.83). The incidences of new-onset multiple organ failure (8.0% vs. 6.5%, P = 1.00), gastrointestinal fistula (29.0% vs. 12.9%, P = 0.10) and bleeding (35.0% vs. 35.5%, P = 1.00), and length of ICU (30.0 vs. 22.0 days, P = 0.61) and hospital stay (42.5 vs. 40.0 days, P = 0.96) were comparable between the two groups. CONCLUSION: Intervention within 4 weeks did not worsen the clinical outcomes in NAP patients complicated by POF.

TiO2 modified orthocortical and paracortical cells having enhanced photocatalytic degradation and photoreduction properties.

In this study, cortical cells resultant from wool fibers were loaded with TiO2 nanoparticles in a hydrothermal process and were then engineered as organic-nonorganic hybrid composite photocatalysts for both photodegradation of organic dyes and photoreduction of heavy metal ions. The microstructure and photocatalytic properties of TiO2 modified cortical cells (i.e. both orthocortical and paracortical cells) were systematically characterized using a series of analytical techniques including FESEM, TEM, element analysis, Mott-Schottky curve, BET specific surface area, Zeta potentials, as well as XRD, FTIR, XPS, DRS, PL, UPS, EDS and ESR spectra. Their photocatalytic performance and trapping experiments of the TiO2 modified cortical cells were measured in the photodegradation of methylene blue (MB) dye and Congo Red (CR) dye as well as the photoreduction of Cr(VI) ions under visible light irradiation. It was found that anatase TiO2 nanoparticles were chemically grafted on the surface of the two cortical cells via O-Ti4+/O-Ti3+ bonds, and that TiO2 nanoparticles were formed inside the orthocortical cells in the hydrothermal process. The TiO2 modified orthocortical and paracortical cells possessed much higher photocatalytic efficiency than the commercially available TiO2 nanoparticle powder, Degussa P25, in the photodegradation of cationic MB dye and photoreduction of Cr(VI) ions, while their photocatalytic efficiency in the photodegradation of anionic CR dye is smaller because of their greater negative Zeta potentials and photogenerated holes as the main reactive radical species. In comparison with the TiO2 modified paracortical cells, the higher photocatalytic efficiency of the TiO2 modified orthocortical cells was demonstrated in the photodegradation of MB dye solution and this might be due to both the S-doped TiO2 nanoparticles infiltrated into the naturally hydrophilic orthocortical cells and the primary reactive radical species of photogenerated holes being trapped in the cells.

Incidence risk of PD-1/PD-L1-related pneumonia and diarrhea in non-small cell lung cancer (NSCLC) patients: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Programmed cell death-1 (PD-1) and programmed cell death ligand-1(PD-L1) inhibitor therapy have been approved for the treatment of many cancers, although their incidence of some side effects was high. We aim to fully investigate the incidence risk of PD-1/PD-L1 inhibitors-related pneumonia and diarrhea in NSCLC patients, as well as treatment-related deaths. METHODS: PubMed, Medline, Cochrane Library, and Clinical trials.gov databases were searched up to Sep 17, 2020, for clinical trials of PD-1 inhibitors and PD-L1 inhibitors in the treatment of NSCLC. Randomized controlled trials and their references were screened. RESULTS: Seventeen trials were included in our meta-analysis, including 11,363 patients. PD-1/PD-L1 inhibitors significantly increased the risk of developing all-grade and high-grade (grade ≥ 3) pneumonia (risk ratio [RR] = 2.28; 95% CI: 1.39-3.76; P < 0.01; RR = 2.38; 95% CI: 1.72-3.29; P < 0.01, respectively). The use of PD-1/PD-L1 inhibitor did not increase the risk of developing all-grade and high-grade diarrhea (RR = 0.79; 95% CI: 0.62-1.01; P = 0.06; RR = 0.96; 95% CI: 0.70-1.31; P = 0.78, respectively). There was no significant difference between the rate of death in PD-1 and PD-L1 inhibitors (P = 0.079). CONCLUSION: These data suggest that PD-1/PD-L1 inhibitors significantly increase the risk of all-grade and high-grade pneumonia in NSCLC patients and PD-1/PD-L1 monotherapy increases the risk of all-grade pneumonia in NSCLC patients compared to PD-1/PD-L1 inhibitor combination regimens. Physicians should pay more attention to NSCLC patients who treated with PD-1/PD-L1 inhibitors.

Single-stage endoscopic endonasal approach for the complete removal of trigeminal schwannomas occupying both the middle and posterior fossae.

To introduce a purely endoscopic endonasal trans-Meckel's cave approach or a transclival approach for trigeminal schwannomas (TSs) involving both the middle and posterior fossae. This retrospective study reviewed the medical records and intraoperative videos of 8 patients with TSs occupying both the middle and posterior fossae who underwent an endoscopic endonasal approach (EEA) between January 2017 and October 2019. All 8 patients received total resection under a single-stage EEA. Six patients underwent endoscopic endonasal resection via a purely trans-Meckel's cave approach, and 2 patients underwent endoscopic endonasal resection via a trans-Meckel's cave approach combined with a transclival approach. There was no surgical-related hemorrhage or mortality and no cerebrospinal fluid leakage. All headache symptoms completely improved postoperatively (n = 3 patients). All cranial nerve (CN) symptoms (CN IX and CN VI) improved postoperatively. The most common preoperative symptom was facial numbness (n = 5 patients); 2 of these 5 patients showed a partial improvement, 1 patient experienced worsening, and 2 patients remained unchanged at the last follow-up. Four patients developed postoperative complications, including CN VI palsy (n = 2), dry eye (n = 2), mastication weakness (n = 1), and facial numbness (n = 2). All complications except for dry eye were relieved at the last follow-up, but the patients with dry eye did not develop corneal keratopathy. The endoscopic endonasal trans-Meckel's cave and transclival approaches provide adequate exposure and improve the rate of total resection for TSs occupying both the middle and posterior fossae with minimal invasion. It may be possible to use these approaches as a safe alternative to conventional surgical approaches.

Two new prenylated coumarins from roots of Zanthoxylum nitidum.

Two new prenylated coumarins, 3'-hydroxytoddanone (1), and isotoddalolactone (2), along with four known analogues (3-6) were isolated from the roots of Zanthoxylum nitidum. Their chemical structures were elucidated based on extensive spectroscopic interpretation and HR-ESI-MS analysis. The absolute configuration of compound 2 was determined by comparing experimental ECD spectrum with that calculated by the time-dependent density functional theory (TDDFT) method. Compounds 4-6 were isolated from the Zanthoxylum genus for the first time. The two new compounds were tested for antiproliferative activities in vitro on the HL-60, K562 and THP-1 cell lines. Compounds 1 and 2 exhibited moderate cell growth inhibitory activities in vitro against human leukemic HL-60 cell lines, with IC50 values of 32.64 and 33.15 µM, respectively.

Quark Transverse Parton Distribution at the Next-to-Next-to-Next-to-Leading Order.

We report a calculation of the perturbative matching coefficients for the transverse-momentum-dependent parton distribution functions for quark at the next-to-next-to-next-to-leading order in QCD, which involves calculation of nonstandard Feynman integrals with rapidity divergence. We introduce a set of generalized integration-by-parts equations, which allows an algorithmic evaluation of such integrals using the machinery of modern Feynman integral calculation.

Identification of a novel LPL nonsense variant and further insights into the complex etiology and expression of hypertriglyceridemia-induced acute pancreatitis.

BACKGROUND: Hypertriglyceridemia (HTG) is a leading cause of acute pancreatitis. HTG can be caused by either primary (genetic) or secondary etiological factors, and there is increasing appreciation of the interplay between the two kinds of factors in causing severe HTG. OBJECTIVES: The main aim of this study was to identify the genetic basis of hypertriglyceridemia-induced acute pancreatitis (HTG-AP) in a Chinese family with three affected members (the proband, his mother and older sister). METHODS: The entire coding and flanking sequences of LPL, APOC2, APOA5, GPIHBP1 and LMF1 genes were analyzed by Sanger sequencing. The newly identified LPL nonsense variant was subjected to functional analysis by means of transfection into HEK-293 T cells followed by Western blot and activity assays. Previously reported pathogenic LPL nonsense variants were collated and compared with respect to genotype and phenotype relationship. RESULTS: We identified a novel nonsense variant, p.Gln118* (c.351C > T), in the LPL gene, which co-segregated with HTG-AP in the Chinese family. We provided in vitro evidence that this variant resulted in a complete functional loss of the affected LPL allele. We highlighted a role of alcohol abuse in modifying the clinical expression of the disease in the proband. Additionally, our survey of 12 previously reported pathogenic LPL nonsense variants (in 20 carriers) revealed that neither serum triglyceride levels nor occurrence of HTG-AP was distinguishable among the three carrier groups, namely, simple homozygotes, compound heterozygotes and simple heterozygotes. CONCLUSIONS: Our findings, taken together, generated new insights into the complex etiology and expression of HTG-AP.

[Endogenous formaldehyde regulates memory].

Formaldehyde is one of the simplest organic small molecules containing C, H and O elements in the early stage of earth's evolution; however, it has been found to be existed in every eukaryotic cell and participate in "one carbon metabolism". Recent studies have shown that formaldehyde may act as a signal molecule to regulate memory formation. After electrical stimulation or learning activity, the levels of formaldehyde in rat brains were increased instantly, and N-methyl-D-aspartate (NMDA) receptor was activated to promote the formation of long-term potentiation (LTP) or spatial memory. On the contrary, after reducing the levels of formaldehyde in the brains, NMDA receptor could not be activated, which was accompanied by the deficits in both LTP and memory. Moreover, in the brains of normal aged rats and APP/PS1 transgenic mice, the concentrations of formaldehyde were abnormally increased, which directly inhibited NMDA receptor activity and impaired spatial memory. This article reviewed the physiological and pathophysiological functions of endogenous formaldehyde in learning and memory.

Management of colonic fistulas in patients with infected pancreatic necrosis being treated with a step-up approach.

BACKGROUND: Colonic fistula is a potentially fatal complication in acute necrotizing pancreatitis (ANP), especially in patients with infected pancreatic necrosis (IPN). The aim of this study was to evaluate the feasibility of a step-up approach including percutaneous catheter drainage (PCD) and continuous negative pressure irrigation (CNPI) in a group of patients with colonic fistula. METHODS: A retrospective review of a prospectively collected data was performed. Data were extracted for patients complicated by colonic fistula from January 2010 to January 2017. RESULTS: A total of 1750 patients were admitted with ANP during the study period. Of these patients, 711 (41%) developed IPN and colonic fistula was present in 132 (19%). A step-up approach was adopted for all patients, with 47% avoiding surgery. The mortality in patients requiring surgery (37%) was higher than that in patients managed non-surgically (19%) constituting an overall mortality rate of 29%. In patients managed conservatively, 92% had spontaneous closure of the fistula. CONCLUSION: Colonic fistula is not a rare complication in ANP occurring in 19% of patients with IPN in the current study. A step-up approach was effective and safe in managing colonic fistula and surgery could be obviated in nearly half of the patients.

Identification of a novel and heterozygous LMF1 nonsense mutation in an acute pancreatitis patient with severe hypertriglyceridemia, severe obesity and heavy smoking.

BACKGROUND: Hypertriglyceridemia (HTG) is one of the most common etiologies of acute pancreatitis (AP). Variants in five genes involved in the regulation of plasma lipid metabolism, namely LPL, APOA5, APOC2, GPIHBP1 and LMF1, have been frequently reported to cause or predispose to HTG. METHODS: A Han Chinese patient with HTG-induced AP was assessed for genetic variants by Sanger sequencing of the entire coding and flanking sequences of the above five genes. RESULTS: The patient was a 32-year-old man with severe obesity (Body Mass Index = 35) and heavy smoking (ten cigarettes per day for more than ten years). At the onset of AP, his serum triglyceride concentration was elevated to 1450.52 mg/dL. We sequenced the entire coding and flanking sequences of the LPL, APOC2, APOA5, GBIHBP1 and LMF1 genes in the patient. We found no putative deleterious variants, with the exception of a novel and heterozygous nonsense variant, c.1024C > T (p.Arg342*; rs776584760), in exon 7 of the LMF1 gene. CONCLUSIONS: This is the first time that a heterozygous LMF1 nonsense variant was found in a HTG-AP patient with severe obesity and heavy smoking, highlighting an important interplay between genetic and lifestyle factors in the etiology of HTG.

Analytical Computation of Energy-Energy Correlation at Next-to-Leading Order in QCD.

The energy-energy correlation (EEC) between two detectors in e^{+}e^{-} annihilation was computed analytically at leading order in QCD almost 40 years ago, and numerically at next-to-leading order (NLO) starting in the 1980s. We present the first analytical result for the EEC at NLO, which is remarkably simple, and facilitates analytical study of the perturbative structure of the EEC. We provide the expansion of the EEC in the collinear and back-to-back regions through next-to-leading power, information which should aid resummation in these regions.

The Toxmatrix: Chemo-Genomic Profiling Identifies Interactions That Reveal Mechanisms of Toxicity.

A chemical genomics "Toxmatrix" method was developed to elucidate mechanisms of cytotoxicity using neuronal models. Quantitative high-throughput screening (qHTS) was applied to systematically screen each toxicant against a panel of 70 modulators, drugs or chemicals that act on a known target, to identify interactions that either protect or sensitize cells to each toxicant. Thirty-two toxicants were tested at 10 concentrations for cytotoxicity to SH-SY5Y human neuroblastoma cells, with results fitted to the Hill equation to determine an IC50 for each toxicant. Thirty-three toxicant:modulator interactions were identified in SH-SY5Y cells for 14 toxicants, as modulators that shifted toxicant IC50 values lower or higher. The target of each modulator that sensitizes cells or protects cells from a toxicant suggests a mode of toxicant action or cellular adaptation. In secondary screening, we tested modulator-toxicant pairs identified from the SH-SY5Y primary screening for interactions in three differentiated neuronal human cell lines: dSH-SY5Y, conditionally immortalized dopaminergic neurons (LUHMES), and neural stem cells. Twenty toxicant-modulator pairs showed pronounced interactions in one or several differentiated cell models. Additional testing confirmed that several modulators acted through their primary targets. For example, several chelators protected differentiated LUHMES neurons from four toxicants by chelation of divalent cations and buthionine sulphoximine sensitized cells to 6-hydroxydopamine and 4-(methylamino)phenol hemisulfate by blocking glutathione synthesis. Such modulators that interact with multiple neurotoxicants suggest these may be vulnerable toxicity pathways in neurons. Thus, the Toxmatrix method is a systematic high-throughput approach that can identify mechanisms of toxicity and cellular adaptation.

Hypoalbuminaemia in antineutrophil cytoplasmic antibody-associated vasculitis: incidence and significance.

OBJECTIVES: Hypoalbuminaemia has been proved to be a biomarker of poor prognosis in many diseases. The objective of this study was to investigate the significance of hypoalbuminaemia in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: Data of 117 AAV patients were analysed retrospectively. The relationship between hypoalbuminaemia and disease severity were studied. The influence of albumin on the pathogenetic role of ANCA was investigated in vitro. RESULTS: Among all patients, 52 had light hypoalbuminaemia (30g/L<=albumin<35g/L) and 40 had nephrotic hypoalbuminaemia (albumin <30g/L). Patients with hypoalbuminaemia had higher inflammation levels and more severe kidney injury than patients without hypoalbuminaemia, but no significant difference of the urinary protein levels were found between patients with nephrotic and light hypoalbuminaemia. Multivariate analysis showed serum albumin correlated with age (r=-0.566, p=0.018), C-reactive protein (r=-0.521, p=0.032) and haemoglobin (r=0.512, p=0.036). Patients with nephrotic hypoalbuminaemia had higher incidence of infection, end stage renal disease and all cause mortality during treatment than patients with light hypoalbuminaemia or normal serum albumin. In vitro study indicated albumin could inhibit the binding between ANCA and neutrophils in a concentration dependent manner. Albumin also inhibited the ANCA-induced respiratory burst and neutrophil extracellular traps formation. CONCLUSIONS: Serum albumin have an inhibitory effect on the binding between ANCA and its antigen. The incidence of hypoalbuminaemia in AAV with kidney involvement is high but is not caused by heavy proteinuria. Hypoalbuminaemia is correlated with the high inflammation level and poor prognosis of AAV. Therapy targeting hypoalbuminaemia might benefit patients with AAV.

Long-Term Outcomes of Unlocking Chinese Patients with Severe Mental Illness.

In 2006, the "unlocking program" was implemented in Hebei province, China to promote the human rights for people with severe mental illness who were physically restrained at home. We assessed the long term outcomes of the "unlocking program" following the provision of hospital and community psychiatric care over 10 years and explored their associated factors. A total of 107 patients with severe mental illness who were "unlocked" in the program were included. Outcome measures were collected with standardized rating scales at 2 separate time points in August 2012 and November 2016. Poor outcome was defined either as being relocked, or missing to follow up or death. In 2012, 36 patients (33.6%) had poor outcomes. Poor outcome was positively associated with follow-up length and less caregiver burden at baseline. By 2016, 53 patients (49.5%) were found to have poor outcomes. There was only a trend of positive association between poor outcome and less caregiver burden at baseline. Poor long-term outcomes were common in patients with severe mental illness following the "unlocking program". Evidence-based treatment strategies and mental health services to improve the outcomes and protect the human rights of patients subjected to being locked in the community are urgently needed.

Characterization of three human cell line models for high-throughput neuronal cytotoxicity screening.

More than 75 000 man-made chemicals contaminate the environment; many of these have not been tested for toxicities. These chemicals demand quantitative high-throughput screening assays to assess them for causative roles in neurotoxicities, including Parkinson's disease and other neurodegenerative disorders. To facilitate high throughput screening for cytotoxicity to neurons, three human neuronal cellular models were compared: SH-SY5Y neuroblastoma cells, LUHMES conditionally-immortalized dopaminergic neurons, and Neural Stem Cells (NSC) derived from human fetal brain. These three cell lines were evaluated for rapidity and degree of differentiation, and sensitivity to 32 known or candidate neurotoxicants. First, expression of neural differentiation genes was assayed during a 7-day differentiation period. Of the three cell lines, LUHMES showed the highest gene expression of neuronal markers after differentiation. Both in the undifferentiated state and after 7 days of neuronal differentiation, LUHMES cells exhibited greater cytotoxic sensitivity to most of 32 suspected or known neurotoxicants than SH-SY5Y or NSCs. LUHMES cells were also unique in being more susceptible to several compounds in the differentiating state than in the undifferentiated state; including known neurotoxicants colchicine, methyl-mercury (II), and vincristine. Gene expression results suggest that differentiating LUHMES cells may be susceptible to apoptosis because they express low levels of anti-apoptotic genes BCL2 and BIRC5/survivin, whereas SH-SY5Y cells may be resistant to apoptosis because they express high levels of BCL2, BIRC5/survivin, and BIRC3 genes. Thus, LUHMES cells exhibited favorable characteristics for neuro-cytotoxicity screening: rapid differentiation into neurons that exhibit high level expression neuronal marker genes, and marked sensitivity of LUHMES cells to known neurotoxicants. Copyright © 2016 John Wiley & Sons, Ltd.