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Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

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bioRxiv2018

Δ9-tetrahydrocannabinol negatively regulates neurite outgrowth and Akt signaling in hiPSC-derived cortical neurons.

Endocannabinoids regulate different aspects of neurodevelopment. In utero exposure to the exogenous psychoactive cannabinoid {Delta}9-tetrahydrocannabinol ({Delta}9-THC), has been linked with abnormal cortical development in animal models. However, much less is known about the actions of endocannabinoids in human neurons. Here we investigated the effect of the endogenous endocannabinoid 2-arachidonoyl glycerol (2AG) and {Delta}9-THC on the development of neuronal morphology and activation of signaling kinases, in cortical glutamatergic neurons derived from human induced pluripotent stem cells (hiPSCs). Our data indicate that the cannabinoid type 1 receptor (CB1R), but not the cannabinoid 2 receptor (CB2R), GPR55 or TRPV1 receptors, is expressed in young, immature hiPSC-derived cortical neurons. Consistent with previous reports, 2AG and {Delta}9-THC negatively regulated neurite outgrowth. Interestingly, acute exposure to both 2AG and {Delta}9-THC inhibited phosphorylation of serine/threonine kinase extracellular signal-regulated protein kinases (ERK1/2), whereas {Delta}9-THC also reduced phosphorylation of Akt (aka PKB). Moreover, the CB1R inverse agonist SR 141716A attenuated the negative regulation of neurite outgrowth and ERK1/2 phosphorylation induced by 2AG and {Delta}9-THC. Taken together, our data suggest that hiPSC-derived cortical neurons express CB1Rs and are responsive to both endogenous and exogenous cannabinoids. Thus, hiPSC-neurons may represent a good cellular model for investigating the role of the endocannabinoid system in regulating cellular processes in human neurons.

neuroscience↗

bioRxiv2018

The causal structure of age-dependent limbic decline: fornix white matter glia damage causes hippocampal grey matter damage, not vice versa.

Aging leads to gray and white matter decline but their causation remains unclear. We explored two broad classes of models of age and dementia risk related brain changes. The first class of models emphasises the importance of gray matter: age and risk-related processes cause neurodegeneration and this causes damage in associated white matter tracts. The second class of models reverses the direction of causation: aging and risk factors cause white matter damage and this leads to gray matter damage. We compared these models with linear mediation analysis and quantitative multi-modal MRI indices (from diffusion, quantitative magnetization transfer and relaxometry imaging) of tissue properties in two limbic structures implicated in age-related memory decline: the hippocampus and the fornix in 166 asymptomatic individuals (aged 38 - 71 years). Aging was associated with apparent glia but not axon density damage in the fornix. Mediation analysis unambiguously supported white matter damage causing gray matter decline; controlling for fornix glia damage, the correlation between age and hippocampal damage disappears, but not vice versa. Fornix and hippocampal tissue loss were both associated with reductions in episodic memory performance. The implications of these findings for neuroglia and neurodegenerative models of aging and late onset dementia are discussed.

neuroscience↗

bioRxiv2018

Phylogenomics of the major tropical plant family Annonaceae using targeted enrichment of nuclear genes

Targeted enrichment and sequencing of hundreds of nuclear loci for phylogenetic reconstruction is becoming an important tool for plant systematics and evolution. Annonaceae is a major pantropical plant family with 109 genera and ca. 2450 species, occurring across all major and minor tropical forests of the world. Baits were designed by sequencing the transcriptomes of five species from two of the largest Annonaceae subfamilies. Orthologous loci were identified. The resulting baiting kit was used to reconstruct phylogenetic relationships at two different levels using concatenated and gene tree approaches: a family wide Annonaceae analysis sampling 65 genera and a species level analysis of tribe Piptostigmateae sampling 29 species with multiple individuals per species. DNA extraction was undertaken mainly on silicagel dried leaves, with two samples from herbarium dried leaves. Our kit targets 469 exons (364 653 bp of sequence data), successfully capturing sequences from across Annonaceae. Silicagel dried and herbarium DNA worked eaually well. We present for the first time a nuclear gene-based phylogenetic tree at the generic level based on 317 supercontigs. Results mainly confirm previous chloroplast based studies. However, several new relationships are found and discussed. We show significant differences in branch lengths between the two large subfamilies Annonoideae and Malmeoideae. A new tribe, Annickieae, is erected containing a single African genus Annickia. We also reconstructed a well resolved species-level phylogenetic tree of the Piptostigmteae tribe. Our baiting kit is useful for reconstructing well supported phylogenetic relationships within Annonaceae at different taxonomic levels. The nuclear genome is mainly concordant with plastome information with a few exceptions. Moreover, we find that substitution rate heterogeneity between the two subfamilies is also found within the nuclear compartment, and not just plastomes and ribosomal DNA as previously shown. Our results have implications for understanding the biogeography, molecular dating and evolution of Annonaceae.

evolutionary biology↗

bioRxiv2018

Evolutionary characteristics of intergenic transcribed regions indicate widespread noisy transcription in the Poaceae

Extensive transcriptional activity occurring in unannotated, intergenic regions of genomes has raised the question whether intergenic transcription represents the activity of novel genes or noisy expression. To address this, we evaluated cross-species and post-duplication sequence and expression conservation of intergenic transcribed regions (ITRs) in four Poaceae species. Most ITR sequences are species-specific. Those found across species tend to be more divergent in expression and have more recent duplicates compared to annotated genes. To assess if ITRs are functional (under selection), machine learning models were established in Oryza sativa (rice) that could distinguish between benchmark functional (phenotype genes) and nonfunctional (pseudogenes) sequences with high accuracy based on 44 evolutionary and biochemical features. Based on the prediction models, 584 rice ITRs (8%) are classified as likely functional that tend to have conserved expression and ancient retained duplicates. However, most ITRs do not exhibit sequence or expression conservation across species or following duplication, consistent with computational predictions that suggest 61% ITRs are not under selection. We outline key evolutionary characteristics that are tightly associated with likely-functional ITRs and provide a framework to identify novel genes to improve genome annotation and move toward connecting genotype to phenotype in crop and model systems.

genomics↗

bioRxiv2018

NAP (davunetide) preferential interaction with dynamic 3-repeat Tau explains differential protection in selected tauopathies

The microtubule (MT) associated protein Tau is instrumental for the regulation of MT assembly and dynamic instability, orchestrating MT-dependent cellular processes. Aberration in Tau post-translational modifications ratio deviation of spliced Tau isoforms 3 or 4 MT binding repeats (3R/4R) have been implicated in neurodegenerative tauopathies. Activity-dependent neuroprotective protein (ADNP) is vital for brain formation and cognitive function. ADNP deficiency in mice causes pathological Tau hyperphosphorylation and aggregation, correlated with impaired cognitive functions. It has been previously shown that the ADNP-derived peptide NAP protects against ADNP deficiency, exhibiting neuroprotection, MT interaction and memory protection. NAP prevents MT degradation by recruitment of Tau and end-binding proteins to MTs and expression of these proteins is required for NAP activity. Clinically, NAP (davunetide, CP201) exhibited efficacy in prodromal Alzheimers disease patients (Tau3R/4R tauopathy) but not in progressive supranuclear palsy (increased Tau4R tauopathy). Here, we examined the potential preferential interaction of NAP with 3R vs. 4R Tau, toward personalized treatment of tauopathies. Affinity-chromatography showed that NAP preferentially interacted with Tau3R protein from rat brain extracts and fluorescence recovery after photobleaching assay indicated that NAP induced increased recruitment of human Tau3R to MTs under zinc intoxication, in comparison to Tau4R. Furthermore, we showed that NAP interaction with tubulin (MTs) was inhibited by obstruction of Tau-binding sites on MTs, confirming the requirement of Tau-MT interaction for NAP activity. The preferential interaction of NAP with Tau3R may explain clinical efficacy in mixed vs. Tau4R pathologies, and suggest effectiveness in Tau3R neurodevelopmental disorders.

neuroscience↗

bioRxiv2018

Can Metabolic Thresholds be used as Exercise Intensity Markers in Adult men with Obesity?

The first aim of the study was to identify the exercise intensity eliciting the highest (FATmax) and the lowest (FATmin) fat oxidation rate in men with obesity. The second aim was to evaluate if FATmax and FATmin correlate with aerobic (AeT) and anaerobic (AnT) thresholds, which in turn could be used as exercise intensity markers. Nineteen adult sedentary men participated in the study. Breath-by-breath analysis was performed throughout the test to assess maximal oxygen consumption (VO2max) with stoichiometric equations used to calculate fat oxidation rate. Pearson correlation coefficient (r), coefficient of determination (R2) and paired t-test were used to evaluate differences between VO2 at AeT and at FATmax and VO2 at AnT and at FATmin, respectively. FATmax and AeT occurred at 42.80 {+/-} 2.68 % of VO2max and 43.02 {+/-} 2.73 % of VO2max, while FATmin and AnT occurred at 53.40 {+/-} 3.65 % of VO2max and 53.38 {+/-} 3.65 % of VO2max, respectively. A high correlations were found between VO2 at FATmax and at AeT (r = 0.86, p < 0.01) and VO2 at FATmin and at AnT (r = 0.99, p < 0.01). The existing correlations suggest that metabolic thresholds may be used as exercise intensity markers in men with obesity.

physiology↗

bioRxiv2018

Spheroid culture of mesenchymal stromal cells results in morpho-rheological properties appropriate for improved microcirculation

Human bone marrow mesenchymal stromal cells (MSCs) have been used in clinical trials for the treatment of systemic inflammatory diseases due to their regenerative and immunomodulatory properties. However, intravenous administration of MSCs is hampered by cell trapping within the pulmonary capillary networks. Here, we hypothesize that traditional twodimensional (2D) plastic-adherent cell expansion fails to result in appropriate morphorheological properties required for cell-circulation. To address this issue, we adapted a novel method to culture MSCs in non-adherent three-dimensional (3D) spheroids (mesenspheres). The biological properties of mesensphere-cultured MSCs remained identical to conventional 2D cultures. Morpho-rheological analyses revealed a smaller size and lower cell stiffness of mesensphere-derived MSCs compared to plastic-adherent MSCs, measured using real-time deformability cytometry (RT-DC) and atomic force microscopy, resulting in an increased ability to pass through micro-constrictions in an ex vivo microcirculation assay. This ability was confirmed in vivo by analysis of cell accumulation in various organ capillary networks after intravenous injection of mesensphere-derived MSCs in mouse. Our findings generally identify cellular morpho-rheological properties as attractive targets to improve microcirculation and specifically suggest mesensphere cultures as a promising approach for optimized MSC-based therapies.

biophysics↗

bioRxiv2018

Tibanna: software for scalable execution of portable pipelines on the cloud

SummaryWe introduce Tibanna, an open-source software tool for automated execution of bioinformatics pipelines on Amazon Web Services (AWS). Tibanna accepts reproducible and portable pipeline standards including Common Workflow Language (CWL), Workflow Description Language (WDL) and Docker. It adopts a strategy of isolation and optimization of individual executions, combined with a serverless scheduling approach. Pipelines are executed and monitored using local commands or the Python Application Programming Interface (API) and cloud configuration is automatically handled. Tibanna is well suited for projects with a range of computational requirements, including those with large and widely fluctuating loads. Notably, it has been used to process terabytes of data for the 4D Nucleome (4DN) Network.\n\nAvailabilitySource code is available on GitHub at https://github.com/4dn-dcic/tibanna.

bioinformatics↗

bioRxiv2018

A Multi-State Birth-Death model for Bayesian inference of lineage-specific birth and death rates

Heterogeneous populations can lead to important differences in birth and death rates across a phylogeny Taking this heterogeneity into account is thus critical to obtain accurate estimates of the underlying population dynamics. We present a new multi-state birth-death model (MSBD) that can estimate lineage-specific birth and death rates. For species phylogenies, this corresponds to estimating lineage-dependent speciation and extinction rates. Contrary to existing models, we do not require a prior hypothesis on a trait driving the rate differences and we allow the same rates to be present in different parts of the phylogeny. Using simulated datasets, we show that the MSBD model can reliably infer the presence of multiple evolutionary regimes, their positions in the tree, and the birth and death rates associated with each. We also present a re-analysis of two empirical datasets and compare the results obtained by MSBD and by the existing software BAMM. The MSBD model is implemented as a package in the Bayesian inference software BEAST2, which allows joint inference of the phylogeny and the model parameters.\n\nSignificance statementPhylogenetic trees can inform about the underlying speciation and extinction processes within a species clade. Many different factors, for instance environmental changes or morphological changes, can lead to differences in macroevolutionary dynamics within a clade. We present here a new multi-state birth-death (MSBD) model that can detect these differences and estimate both the position of changes in the tree and the associated macroevolutionary parameters. The MSBD model does not require a prior hypothesis on which trait is driving the changes in dynamics and is thus applicable to a wide range of datasets. It is implemented as an extension to the existing framework BEAST2.

evolutionary biology↗

bioRxiv2018

Adipokines contribute to central-obesity related reductions in myelin-sensitive MRI indices in the fornix.

Midlife obesity is a risk factor of late onset Alzheimers disease (LOAD) but why this is the case remains unknown. As systemic inflammation is involved in both conditions, one possibility is that obesity-related neuroinflammation may contribute to the development of LOAD. Neuroinflammation is closely linked to white matter myelin loss, and this can be measured in vivo with quantitative magnetization transfer (qMT) imaging. Here, we investigated whether differences in obesity measures, i.e., in Waist Hip Ratio (WHR), abdominal visceral and subcutaneous fat volume fractions and Body Mass Index (BMI), were associated with reductions in qMT indices of apparent myelin in temporal white matter pathways involved in LOAD (i.e., the fornix, the parahippocampal cingulum and the uncinate fasciculus compared with whole brain and cortico-spinal white matter) in 166 cognitively healthy individuals (38-71 years of age). Obesity-related effects on myelin-sensitive markers were contrasted with differences in apparent axon density from dual-shell diffusion Neurite Orientation Dispersion and Density Imaging (NODDI). Differences in WHR and in visceral fat volume fractions were negatively correlated with differences in qMT estimates of apparent myelin and tissue metabolism in the fornix but not with any other microstructural components. These correlations were not explained by demographic (age, sex, education), health (hypertension, alcohol consumption, sedentary lifestyle) or genetic (APOE genotype, family history of dementia) risk factors of LOAD. Furthermore, differences in the ratio of plasma concentrations of leptin and adiponectin were also positively correlated with differences in C-Reactive Protein concentrations, and contributed significantly to the correlations between central obesity and myelin-sensitive metrics in the fornix. These results are consistent with the view that visceral fat-related chronic inflammation may damage white matter myelin in limbic regions, known to be vulnerable to LOAD pathology.

neuroscience↗

bioRxiv2018

Specificity of RNA folding and its association with evolutionarily adaptive mRNA secondary structure

Secondary structure is a fundamental feature for both noncoding and messenger RNA. However, our understandings about the secondary structure of mRNA, especially for the coding regions, remain elusive, likely due to translation and the lack of RNA binding proteins that sustain the consensus structure, such as those bind to noncoding RNA. Indeed, mRNA has recently been found to bear pervasive alternative structures, whose overall evolutionary and functional significance remained untested. We hereby approached this problem by estimating folding specificity, the probability that a fragment of RNA folds back to the same partner once re-folded. We showed that folding specificity for mRNA is lower than noncoding RNA, and displays moderate evolutionary conservation between orthologs and between paralogs. More importantly, we found that specific rather than alternative folding is more likely evolutionarily adaptive, since it is more frequently associated with functionally important genes or sites within a gene. Additional analysis in combination with ribosome density suggests the capability of modulating ribosome movement as one potential functional advantage provided by specific folding. Our findings revealed a novel facet of RNA structome with important functional and evolutionary implications, and points to a potential way of disentangling mRNA secondary structures maintained by natural selection from molecular noise.

evolutionary biology↗

bioRxiv2018

The Hex-Maze: A previous knowledge task for mice

New information is rarely learned in isolation, instead most of what we experience can be incorporated into or uses previous knowledge networks in some form. However, most rodent laboratory tasks assume the animal to be naive with no previous experience influencing the results. Previous knowledge in form of a schema can facilitate knowledge acquisition and accelerate systems consolidation: memories become more rapidly hippocampal independent and instead rely more on the prefrontal cortex. Here, we developed a new spatial navigation task where food locations are learned in a large, gangway maze - the HexMaze. Analysing performance across sessions as well as on specific trials, we can show simple memory effects as well as multiple effects of previous knowledge accelerating both online learning and performance increases over offline periods. Importantly, we are the first to show that schema build-up is dependent on how much time passes, not how often the animal is trained.

animal behavior and cognition↗

bioRxiv2018

Artificial neural network filters for enhancing 3D optical microscopy images of neurites

The ability to extract accurate morphology of labeled neurons from microscopy images is crucial for mapping brain connectivity and for understanding changes in connectivity that underlie learning and memory formation. There are, however, two problems, specific to optical microscopy imaging of neurons, which make accurate neuron tracing exceedingly challenging: (i) neurites can appear broken due to inhomogeneous labeling and (ii) neurites can appear fused in 3D due to limited resolution. Here, we propose and evaluate several artificial neural network (NN) architectures and conventional image enhancement filters with the aim of solving both problems. To evaluate the effects of filtering, we examine the following four image quality metrics: normalized intensity in the cross-over regions between neurites, radius of neurites, coefficient of variation of intensity along neurites, and local background to neurite intensity ratio. Our results show that NN filters, trained on optimized semi-manual traces of neurites, can significantly outperform conventional filters. In particular, U-Net based filtering can virtually eliminate background intensity, while also reducing radius of neurites by 23% to nearly 1 voxel, decreasing intensity in the cross-over regions between neurites by 22%, and reducing variations in intensity along neurites by 26%. These results suggest that including a NN filtering step, which does not require much extra time or computing power, can be beneficial for neuron tracing projects.

neuroscience↗

bioRxiv2018

Bayesian Estimation of Species Divergence Times Using Correlated Quantitative Characters

Discrete morphological data have been widely used to study species evolution, but the use of quantitative (or continuous) morphological characters is less common. Here, we implement a Bayesian method to estimate species divergence times using quantitative characters. Quantitative character evolution is modelled using Brownian diffusion with character correlation and character variation within populations. Through simulations, we demonstrate that ignoring the population variation (or population "noise") and the correlation among characters leads to biased estimates of divergence times and rate, especially if the correlation and population noise are high. We apply our new method to the analysis of quantitative characters (cranium landmarks) and molecular data from carnivoran mammals. Our results show that time estimates are affected by whether the correlations and population noise are accounted for or ignored in the analysis. The estimates are also affected by the type of data analysed, with analyses of morphological characters only, molecular data only, or a combination of both; showing noticeable differences among the time estimates. Rate variation of morphological characters among the carnivoran species appears to be very high, with Bayesian model selection indicating that the independent-rates model fits the morphological data better than the autocorrelated-rates model. We suggest that using morphological continuous characters, together with molecular data, can bring a new perspective to the study of species evolution. Our new model is implemented in the MCMCtree computer program for Bayesian inference of divergence times.

evolutionary biology↗

bioRxiv2018

jouvence, a new small nucleolar RNA required in the gut extends lifespan in Drosophila

Longevity is influenced by various genetic and environmental factors, but the underlying mechanisms remain poorly understood. Here, we functionally characterise a new Drosophila small nucleolar RNA (snoRNA), named jouvence whose loss of function dramatically reduces lifespan. A transgene containing the genomic region of jouvence rescues the longevity in mutant, while its overexpression in wild-type flies increases lifespan. Jouvence is expressed in epithelial cells of the gut. Targeted expression of jouvence specifically in the enterocytes increases lifespan, indicating that its role in the control of longevity takes place in these cells. A transcriptomic analysis performed from the gut reveals that several genes are either up-or down-regulated in mutant indicating that the snoRNA-jouvence might be involved in transcriptional control. Finally, since snoRNAs are structurally and functionally well conserved throughout evolution, we identified putative jouvence orthologue in mammals including humans, suggesting that its function in longevity might be conserved through evolution.

genetics↗

bioRxiv2018

Investigation of novel functions of three genes in oriental river prawn, Macrobrachium nipponense: Molecular Cloning, Expression, and In situ Hybridization Analysis

Three genes were predicted to be potentially involved in the male sexual development in M. nipponense, including the Gem-associated protein 2-like isoform X1 (GEM), Ferritin peptide, and DNA polymerase zeta catalytic subunit (Rev3). In this study, we aimed to investigate their novel functions in depth. The full-length cDNA sequence of Mn-GEM was 1,018 bp, encoding 258 amino acids. The partial Mn-Rev3 cDNA sequence was 6,832 bp, encoding 1,203 amino acids. Tissue distribution indicated that all of these three genes have higher expression level in testis and androgenic gland, implying their novel functions in male sexual development. In situ hybridization analysis further confirmed the novel roles of these three genes. Rev3 promote the testis development during the whole reproductive cycle, while GEM and ferritin only promote the activation of testis development. Besides, these three genes play essential roles in funicular structure development surrounding the androgenic gland cells, which promote and support the formation of androgenic gland cells. The expression in hepatopancreas cells also suggested their role in immune system in M. nipponense. This study advances our understanding of male sexual development in M. nipponense, as well as providing the basis for further studies of male sexual differentiation and development in crustaceans.

zoology↗

bioRxiv2018

Comparisons of a Novel Air Sampling Filter Material, Wash Buffers and Extraction Methods in the Detection and Quantification of Influenza Virus

Quantification of aerosolized influenza virus is used for determining inhalation exposure. Several bioaerosol samplers and analytical methods have been used; however, the detection and quantification of influenza virus among aerosol samples remains challenging. Therefore, improved viral aerosol measurement methods are needed. This study evaluated influenza virus recovery among three filter types polytetrafluoroethylene, polyvinylchloride and polystyrene. Polytetrafluoroethylene, polyvinylchloride are fabricated filter materials and commonly used in the scientific literature to sample for viral aerosols. A novel, electrospun polystyrene filter material may improve viral aerosol recovery during filter-based air sampling. The filter materials were compared across the following conditions: treated with or without air, filter wash buffer (HBSS or PBS), and viral RNA extraction method (QIAamp Viral RNA Mini Kit or Trizol). Twenty trials were completed in a chamber and samples were analyzed using RT-qPCR. Viral recovery was significantly different (p-value < .0001) by filter type. Polystyrene filter use resulted in recovery of the most viral RNA. Air sampling did not affect the recovery of viral RNA from the filter materials (p-values > 0.05). Viral RNA concentrations were significantly different across extraction methods for all comparisons (p-values < 0.05). Our results demonstrated that the novel polystyrene filter material resulted in the highest concentration of extracted RNA compared to the commonly used polytetrafluoroethylene and polyvinylchloride, which we speculate may be related to the chemical composition of the filter material (e.g., polystyrene is an aromatic hydrocarbon whereas polytetrafluoroethylene and polyvinylchloride contain more polar, and thus potentially reactive, carbon-halogen bonds). Air sampling did not have an effect on viral RNA recovery. Using Hanks Balanced Salt Solution with QIAamp Viral RNA Mini Kit, and Phosphate-buffered saline with the Trizol extraction, resulted in the most viral RNA recovery.

microbiology↗

bioRxiv2018

Calotropis gigantea extract induces apoptosis through extrinsic/intrinsic pathways and upregulation of reactive oxygen species in non-small-cell lung cancer cells

BackgroundCalotropis gigantea (CG) plant grows in Asia and tropical Africa. However, the precise mechanisms of its anticancer effects have not yet been examined in human non-small cell lung cancer (NSCLC) cells, A549 and NCI-H1299 cells.\n\nPurposeThis study was focused on the anti-cancer effects of CG extract on non-small cell lung cancer (NSCLC) cells.\n\nMethodsThe cytotoxic effects of CG extract on NSCLC, A549 and NCI-H1299 cells, were detected by MTS assay, microscope and DAPI staining. Apoptosis was determined by annexin V-FITC/PI staining, cell cycle analysis, western blotting, quantitative polymerase chain reaction, and JC-1 staining.\n\nResultsFirst, CG showed significant dose-dependent cytotoxicity in NSCLC, A549, and NCI-H1299 cells. In addition to induction of caspase-8 processing, CG induced apoptosis by upregulating mRNA expression levels of extrinsic pathway molecules such as Fas, Fas ligand (FasL), Fas-associated protein with death domain (FADD) and death receptor 5 (DR5). Also, mitochondrial membrane potential (MMP) was collapsed, and intrinsic pathway molecules such as poly (ADP-ribose) polymerase (PARP), caspase-3, and caspase-9 were processed by CG. Moreover, reactive oxygen species (ROS) were generated in a CG dose-dependent manner, and inhibition of ROS by NAC, ROS scavenger, recovered A549 and NCI-H1299 cell viability.\n\nConclusionThese results indicate that CG causes apoptosis by activating the extrinsic and intrinsic pathways and generating ROS in NSCLC cells. These results suggest that CG can be used as a lung cancer therapeutic agent.

cancer biology↗