Biology subjects

Luo, Q.

Publications and source records attributed to Luo, Q..

At least 91 records · Page 5Linked to original sources

bioRxiv2021

Contribution of climate models and APSIM phenological parameters to uncertainties in spring wheat simulations: application of SUFI-2 algorithm in northeast Australia

We used SUFI-2 for the first time to calibrate the phenology module of the APSIM-wheat model for 10 spring wheat cultivars cultivated in northeast Australia (south-eastern Queensland). Calibration resulted in an average RMSE of 5.5 d for developmental stages from stem elongation up to flowering. Projections from 33 climate models under the representative concentration pathway 8.5 were used for simulations at 17 sites. Using adapted sowing times, we simulated significantly shorter crop cycles and grain yield improvements for the period 2036-2065 relative to 1990-2019 for three selected cultivars (Hartog, Scout and Gregory). Photoperiod and vernalisation sensitivities were shown to be the largest and smallest contributors to total uncertainties in the simulated flowering day and grain yield. Uncertainties in climate models had a relatively minor contribution to the total uncertainties in the simulated values of target traits. This contribution significantly increased when climate change impact on the target traits was estimated.

plant biology↗

bioRxiv2021

Single-cell and single-variant resolution analysis of clonal evolution in human liver cancer

Genetic heterogeneity of tumor is closely related to clonal evolution, phenotypic diversity and treatment resistance. Such heterogeneity has been characterized in liver cancer at single-cell sub-chromosomal scale, and a more precise single-variant resolution analysis is lacking. Here we employed a strategy to analyze both the single-cell genomic mutations and transcriptomic changes in 5 patients with liver cancer. Target sequencing was done for a total of 480 single cells in a patient-specific manner. DNA copy number status of point mutations was obtained from single-cell mutational profiling. The clonal structures of liver cancers were then uncovered at single-variant resolution, and mutation combinations in single cells enabled reconstruction of their evolutionary history. A common origin but independent evolutionary fate was revealed for primary liver tumor and intrahepatic metastatic portal vein tumor thrombus. The mutational signature suggested early evolutionary process may be related to specific etiology like aristolochic acids. By parallel single-cell RNA-Seq, the transcriptomic phenotype was found to be related with genetic heterogeneity in liver cancer. We reconstructed the single-cell and single-variant resolution clonal evolutionary history of liver cancer, and dissection of both genetic and phenotypic heterogeneity provides knowledge for mechanistic understanding of liver cancer initiation and progression.

genomics↗

bioRxiv2020

Whole-brain connectivity atlas of glutamatergic and GABAergic neurons in mouse dorsal and median raphe nucleus

The dorsal raphe nucleus (DR) and median raphe nucleus (MR) contain populations of glutamatergic and GABAergic neurons regulating diverse behavioral functions. Their whole-brain input-output circuits remain incompletely understood. We used viral tracing combined with fluorescence micro-optical sectioning tomography to generate a comprehensive whole-brain atlas of inputs and outputs of glutamatergic and GABAergic neurons in the DR and MR. We discovered that these neurons receive inputs from similar upstream brain regions. The glutamatergic and GABAergic neurons in the same raphe nucleus have divergent projection patterns with differences in critical brain regions. Specifically, MR glutamatergic neurons project to the lateral habenula via multiple pathways. Correlation and cluster analysis indicated that glutamatergic and GABAergic neurons in the same raphe nucleus receive inputs from heterogeneous neurons in upstream brain regions and send different collateral projections. This connectivity atlas provides insights into the cell heterogeneity, anatomical connectivity and behavioral functions of the raphe nucleus.

neuroscience↗

bioRxiv2020

ORMDL1 is upregulated and associated with favorable outcome in colorectal cancer

BackgroundORMDL1 gene encodes a transmembrane protein for endoplasmic reticulum and is known as crucial negative regulator for sphingolipid biogenesis. However, it has been rarely studied in tumor-related context. Therefore, its prognostic value and functional significance in colorectal cancer (CRC) remain to be explored. MethodsTCGA CRC cohort analysis, qRT-PCR, and immunohistochemistry (IHC) were used to examine the ORMDL1 expression level. The association between ORMDL1 expression and various clinical characteristics were analyzed by Chi-square tests. CRC patients overall survival (OS) was analyzed by Kaplan-Meier analysis. In vitro and in vivo cell-based assays were performed to explore the role of ORMDL1 in cell proliferation, invasion and migration. Transcriptional changes of cells either with ORMDL1 knockdowned or overexpressed were compared and analyzed. ResultsORMDL1 was upregulated in CRC tissues either in TCGA cohort or in our cohort. Interestingly, its expression was significantly lower in patients with metastasis compared to patients without metastasis, and high expression group had longer OS than low expression group. Knockdown of ORMDL1 expression can promote proliferation, colony formation and invasion, while attenuate migration in CRC cell lines. In opposite, forced overexpression of ORMDL1 reduced cell proliferation, colony formation and invasion, while enhanced cell migration. Epithelial-to-mesenchymal transition (EMT) related genes were enriched among differentially expressed genes when ORMDL1 was knockdowned in cells, which was consistent with morphologic change by microscopy observation. Finally, stable knockdown of ORMDL1 can promote cancer cell proliferation in vivo to some extent. ConclusionORMDL1 is upregulated and may serve as biomarker to predict favourable outcome in colorectal cancer.

cancer biology↗

bioRxiv2020

Overexpression of EiKCS confers paraquat-tolerance in rice (Oryza sativa L.) by promoting polyamine pathway

Paraquat is an important bipyridine herbicide by acting on the photosynthetic system of the plants and generating reactive oxygen species leading to cell death, whereas the mechanism of the paraquat resistance remains to be explored. In this study, a putative paraquat-resistant gene EiKCS from goosegrass (Eleusine indica L.) was isolated and overexpressed in a transgenic rice (Oryza sativa L.). This transgenic rice (KCSox) was treated by exogenous spermidine and paraquat and then was analyzed by qualitative and quantitative proteomics. Overexpressing of EiKCS enhanced paraquat tolerance in KCSox by the accumulation of endogenous polyamines whose dominant presences of polyamines benzoylation derivatizations in rice were C18H20N2O2, C28H31N3O3, and C38H42N4O4. The mechanism underlying the improving tolerance enhanced antioxidant capacity of ROS systems and light-harvesting in photosynthesis in KCSox rice leaves to reducing paraquat toxicity. The protein {beta}-Ketoacyl-CoA Synthase (EiKCS) encoded by the EiKCS gene promoted the synthesis and metabolism of proteins of the polyamine pathway. Three cofactors CERs were identified and positively correlated with the function of EiKCS on very-long-chain fatty acids (VLCFAs) biosynthesis via promoting the polyamine pathway and inhibiting the links with the TCA pathway and fatty acid pathway to responding to the paraquat tolerance in the KCSox rice, which also caused the prolongation of the overproduction of spermine and a transient increase of intracellular malondialdehyde (MDA). These results expanded the polyamines pathway manipulated in cereals using genetic engineering to clarify the mechanism of paraquat-tolerance. One Sentence SummaryA putative paraquat-resistant EiKCS gene from the goosegrass overexpressing in the rice resulted in the accumulation of polyamines, especially the spermine, and promoted the proteins in polyamine pathways by its EiKCS protein under paraquat stress.

physiology↗

bioRxiv2020

Effect of lysergic acid diethylamide (LSD) on reinforcement learning in humans

The non-selective serotonin 2A (5-HT2A) receptor agonist lysergic acid diethylamide (LSD) holds promise as a treatment for some psychiatric disorders. Psychedelic drugs such as LSD have been suggested to have therapeutic actions through their effects on learning. The behavioural effects of LSD in humans, however, remain largely unexplored. Here we examined how LSD affects probabilistic reversal learning in healthy humans. Healthy volunteers received intravenous LSD (75g in 10 mL saline) or placebo (10mL saline) in a within-subjects design and completed a probabilistic reversal learning task. Participants had to learn through trial and error which of three stimuli was rewarded most of the time, and these contingencies switched in a reversal phase. Computational models of reinforcement learning were fitted to the behavioural data to assess how LSD affected the updating ("learning rates") and deployment ("reinforcement sensitivity") of value representations during choice, as well as "stimulus stickiness", which assays choice repetition irrespective of reinforcement history. Conventional measures assessing sensitivity to immediate feedback ("win-stay" and "lose-shift" probabilities) were unaffected, whereas LSD increased the impact of the strength of initial learning on perseveration. Computational modelling revealed that the most pronounced effect of LSD was enhancement of the reward learning rate. The punishment learning rate was also elevated. Stimulus stickiness was decreased by LSD, reflecting heightened exploratory behaviour, while reinforcement sensitivity was unaffected. Increased reinforcement learning rates suggest LSD induced a state of heightened plasticity. These results indicate a potential mechanism through which revision of maladaptive associations could occur in the clinical application of LSD. Significance statementThe psychedelic ("mind-manifesting") drug LSD holds promise for the treatment of some psychiatric disorders. Theories have postulated its therapeutic potential centres on enhancing learning and flexible thinking. Here we provide substantiating empirical evidence by examining the computations underlying behaviour as healthy volunteers learned through trial and error under LSD. Viewing choice as based on representations of an actions value, LSD increased the speed at which value was updated following feedback, which was more pronounced following reward than punishment. Behaviour was also more exploratory under LSD, irrespective of the outcome of actions. These results indicate that LSD impacted a fundamental belief-updating process inherent in the brain which can be leveraged to revise maladaptive associations characteristic of a range of mental disorders.

neuroscience↗

bioRxiv2020

A prospective longitudinal study shows putamen volume is associated with moderate amphetamine use and resultant cognitive impairments

BackgroundAmphetamine-type stimulants (ATS) have become a critical public health issue. Animal models have indicated a clear neurotoxic potential of ATSs. In humans, chronic use has been associated with cognitive deficits and structural brain abnormalities. However, cross-sectional retrospective designs in chronic users cannot truly determine the causal direction of the effects. MethodsIn a prospective-longitudinal study design cognitive functioning and brain structure were assessed at baseline and at 12-months follow-up in occasional ATS users (cumulative lifetime use <10 units at baseline). ResultsExamination of change-scores between the initial examination and follow-up revealed declined verbal memory performance and putamen volume in users with high relative to low interim ATS exposure. In the entire sample interim ATS use, memory decline and putamen volume reductions were strongly associated. ConclusionsThe present findings support the hypothesis that ATS use is associated with deficient dorsal striatal morphology which might reflect alterations in dopaminergic pathways. More importantly, these findings strongly suggest that even occasional, low-dose ATS use disrupts striatal integrity and cognitive functioning.

neuroscience↗

bioRxiv2020

Alisertib exerts KRAS allele specific anticancer effects in colorectal cancer

Colorectal cancer (CRC) is a common cancer causing substantial mortality and morbidity worldwide. Oncogene RAS mutations occur notably in [~]45% of CRCs, associated with a poor prognosis. KRAS is subject to multiple tiers of regulation, including kinase. Aurora kinases has been implicated in many types of tumor onsets and progression, making them as a promising therapeutic targets. Alisertib (ALS), selectively inhibits Aurora kinase A (AURKA) and exerts potent anticancer activities in vitro and in vivo studies, but the latent anticancer effect of ALS on CRC remains unclear in the context of different KRAS mutations. This study aimed to assess the effects of ALS on RAS signaling pathway in a panel of CRC lines expressing different KRAS alleles, including Caco-2 (KRAS WT), Colo-678 (KRAS G12D), SK-CO-1 (KRAS G12V), HCT116 (KRAS G13D), CCCL-18 (KRAS A146T), and HT29 (BRAF V600E). The results showed that ALS modulated the active form of KRAS in a RAS allele specific manner across the panel of CRC lines; ALS differentially regulated RAS signal via PI3K/Akt and MAPK pathways; and ALS induced apoptosis and autophagy in a RAS allele specific manner. Of note, in combination of ALS and MEK inhibitor, selumetinib, enhanced ALS regulatory effects in CRC lines in a RAS allele specific manner on apoptosis, autophagy, and cell growth. Taken together, this study suggests that ALS differentially regulates RAS signaling pathway and manipulates cell apoptosis and autophagy in RAS allele specific manner. The combinatorial approach of ALS and MEK inhibitor may represent a new therapeutic strategy for precision therapy of CRC in a RAS allele manner.

cancer biology↗

bioRxiv2020

Roles of Signaling Compounds and WRKY31 in the Defense of Pinus massoniana L. Against Dendrolimus punctatus

Dendrolimus punctatus is an important pest affecting Masson pine (Pinus massoniana L.) forests and can cause serious economic and ecological losses. WRKY transcription factors play important roles in coping with various environmental stresses. In particular, recent studies have shown that WRKY transcription factors play an important role in plant responses against herbivorous insects. However, the mechanisms underlying the actions of these genes in the defense responses of P. massoniana L. are still unclear. Our previous study provided evidence that WRKY may play an important role in the insect resistance of P. massoniana L. In this study, application of semiochemicals such as exogenous hormones and Ca2+ by spraying increased the concentrations of endogenous hormones, terpenoid synthases, and volatile substances in P. massoniana L. and effectively improved its resistance to D. punctatus. After analyzing the WRKY family of P. massoniana L., the PmWRKY31 gene was selected and studied. Yeast two-hybrid assays showed that the LP8 gene interacted with PmWRKY31. Fluorescence-based quantitative polymerase chain reaction showed that after treatment with exogenous hormones and Ca2+, the expression levels of the PmWRKY31 gene, hormonal signal-related genes, and terpene biosynthetic pathway-related genes were significantly increased, whereas the expression of the LP8 gene was decreased. Therefore, the PmWRKY31 and LP8 genes affected downstream gene expression by positively and negatively regulating the hormone signaling pathways, respectively. This result provides theoretical support for the involvement of WRKY transcription factors in the insect resistance of P. massoniana L. through their regulation of hormone signaling.

plant biology↗

bioRxiv2020

The mouse cortico-basal ganglia-thalamic network

The cortico-basal ganglia-thalamic loop is one of the fundamental network motifs in the brain. Revealing its structural and functional organization is critical to understanding cognition, sensorimotor behavior, and the natural history of many neurological and neuropsychiatric diseases. Classically, the basal ganglia is conceptualized to contain three primary information output channels: motor, limbic, and associative. However, given the roughly 65 cortical areas and two dozen thalamic nuclei that feed into the dorsal striatum, a three-channel view is overly simplistic for explaining the myriad functions of the basal ganglia. Recent works from our lab and others have subdivided the dorsal striatum into numerous functional domains based on convergent and divergent inputs from the cortex and thalamus. To complete this work, we generated a comprehensive data pool of [~]700 injections placed across the striatum, external globus pallidus (GPe), substantia nigra pars reticulata (SNr), thalamic nuclei, and cortex. We identify 14 domains of SNr, 36 in the GPe, and 6 in the parafascicular and ventromedial thalamic nuclei. Subsequently, we identify 6 parallel cortico-basal ganglia-thalamic subnetworks that sequentially transduce specific subsets of cortical information with complex patterns of convergence and divergence through every elemental node of the entire cortico-basal ganglia loop. These experiments reveal multiple important novel features of the cortico-basal ganglia network motif. The prototypical sub-network structure is characterized by a highly interconnected nature, with cortical information processing through one or more striatal nodes, which send a convergent output to the SNr and a more parallelized output to the GPe; the GPe output then converges with the SNr. A domain of the thalamus receives the nigral output, and is interconnected with both the striatal domains and the cortical areas that filter into its nigral input source. This study provides conceptual advancement of our understanding of the structural and functional organization of the classic cortico-basal ganglia network.

neuroscience↗

bioRxiv2020

The chaos in calibrating crop models

Calibration, the estimation of model parameters based on fitting the model to experimental data, is among the first steps in many applications of system models and has an important impact on simulated values. Here we propose and illustrate a novel method of developing guidelines for calibration of system models. Our example is calibration of the phenology component of crop models. The approach is based on a multi-model study, where all teams are provided with the same data and asked to return simulations for the same conditions. All teams are asked to document in detail their calibration approach, including choices with respect to criteria for best parameters, choice of parameters to estimate and software. Based on an analysis of the advantages and disadvantages of the various choices, we propose calibration recommendations that cover a comprehensive list of decisions and that are based on actual practices. HighlightsO_LIWe propose a new approach to deriving calibration recommendations for system models C_LIO_LIApproach is based on analyzing calibration in multi-model simulation exercises C_LIO_LIResulting recommendations are holistic and anchored in actual practice C_LIO_LIWe apply the approach to calibration of crop models used to simulate phenology C_LIO_LIRecommendations concern: objective function, parameters to estimate, software used C_LI

plant biology↗

bioRxiv2020

Genome-Wide Mapping of Cisplatin Damaged Gene Loci

Cisplatin is a DNA targeting anticancer drug, yet its damaged gene loci have remained unclear. In the present work, combining affinity isolation and high throughput sequencing, we genome-widely mapped 17729 gene loci containing platination lesions, which mainly function as enzymes, transcription regulators, transporters and kinases, and of which 445 genes account for 71% of potential gene targets for cancer therapy reported in the literature. The most related core signaling pathway, disease and tissue toxicity of 7578 genes with an enrichment fold (EFG) of >12, where EFG refers to the ratio of total read counts of a gene detected in cells with and without cisplatin treatment, are sperm motility, cancer and hepatotoxicity with association P values of < 1x10-22. Among 616 kinase genes damaged by cisplatin, 427 are protein kinases which account for 82% of putative protein kinases, suggesting that cisplatin may act as broad-spectrum protein kinase inhibitor. Western Blot assays verified that expression of 8 important protein kinase genes was significantly reduced due to cisplatin damage. SPAG9 is closely related to 147 of 361 cancer diseases which the cisplatin damaged genes are associated with and was severely damaged by cisplatin. Given SPAG9 abundantly expresses JIP-4, a upstream mediator of protein kinase signaling, in testis, it may be responsible for the high sensitivity of testicular cancer to cisplatin, thus being a potential therapeutic target for precise treatment of testicular cancer. These findings provide novel insights into better understanding in molecular mechanism of anticancer activity and toxicity of cisplatin, more importantly inspire further studies in prioritizing gene targets for precise treatment of cancers.

pharmacology and toxicology↗

bioRxiv2020

Visual mode switching learned through experience

When the environment changes, vision adapts to maintain accurate perception. For repeatedly encountered environments, learning to switch immediately to prior adaptive states would be beneficial, but past work remains inconclusive. We tested if the visual system can learn such visual mode switching for a strongly tinted environment, where adaptation causes the dominant hue to fade over time. Eleven observers wore red glasses for five one-hour periods per day, for five days. Color adaptation was measured by asking observers to identify "unique yellow", appearing neither reddish nor greenish. As expected, the world appeared less and less reddish during the one-hour periods of glasses wear. Critically, across days the world also appeared significantly less reddish immediately after donning the glasses. This indicates that the visual system learned to shift rapidly to a partially adapted state, switching modes to stabilize color vision. Mode switching likely provides a general strategy to optimize perceptual processes.

neuroscience↗

bioRxiv2020

Towards More Reliable Unsupervised Tissue Segmentation Via Integrating Mass Spectrometry Imaging and Hematoxylin-Erosin Stained Histopathological Image

Mass Spectrometry Imaging (MSI) provides a useful tool to divide a tissue section into sub-regions with similar molecular profiles, namely tissue segmentation. However, owing to the lack of ground truth, there is no reliable evaluation approach to assess the validity of unsupervised segmentation outcomes of MSI. We propose a novel solution grounded on a presumption that a segmentation is reliable if it can be reproduced using distinct bio-information extracted from independent sources. Specifically, besides molecular information from MSI data, we also obtain morphological information over a tissue section from its Hematoxylin-Erosin (H&E) stained histopathological image. MSI has high molecular specificity but low spatial resolving power, the H&E image has no molecular specificity but it can capture microscopic details of the tissue with a spatial resolution two magnitudes higher than MSI. The whole H&E image is split into an array of small patches, which correspond to the spatial pixels of MSI. A spectrum of informative morphological features is computed iteratively for each patch and spatial segmentation can be generated by clustering the patches based on their morphological similarities. Adjusted Mutual Information (AMI) score measures the degree of agreement between MSI-based and H&E image-based segmentation outcomes, which is defined by us as an objective and quantitative evaluation metric of segmentation validity. We investigated various candidate morphological features: a combination of Deep Convolution Neural Network (DCNN) features and handcrafted Threshold Adjacency Statistics (TAS) features finally stood out. The most appropriate number of tissue segments was also determined according to AMI score. Moreover, we introduced Co-Clustering algorithm to MSI data to simultaneously group m/z variables and spatial pixels, so potential biomarkers associated to each sub-region were discovered without the need of further analysis. Eventually, by integrating the segmentation outcomes based on MSI and H&E image data, the confidence level of the segment assignment was displayed for each pixel, which offered a much more informative and compelling way to present the segmentation results.

bioinformatics↗

bioRxiv2020

Multi-model evaluation of phenology prediction for wheat in Australia

Predicting wheat phenology is important for cultivar selection, for effective crop management and provides a baseline for evaluating the effects of global change. Evaluating how well crop phenology can be predicted is therefore of major interest. Twenty-eight wheat modeling groups participated in this evaluation. Our target population was wheat fields in the major wheat growing regions of Australia under current climatic conditions and with current local management practices. The environments used for calibration and for evaluation were both sampled from this same target population. The calibration and evaluation environments had neither sites nor years in common, so this is a rigorous evaluation of the ability of modeling groups to predict phenology for new sites and weather conditions. Mean absolute error (MAE) for the evaluation environments, averaged over predictions of three phenological stages and over modeling groups, was 9 days, with a range from 6 to 20 days. Predictions using the multi-modeling group mean and median had prediction errors nearly as small as the best modeling group. About two thirds of the modeling groups performed better than a simple but relevant benchmark, which predicts phenology by assuming a constant temperature sum for each development stage. The added complexity of crop models beyond just the effect of temperature was thus justified in most cases. There was substantial variability between modeling groups using the same model structure, which implies that model improvement could be achieved not only by improving model structure, but also by improving parameter values, and in particular by improving calibration techniques.

plant biology↗

bioRxiv2020

Structural insight into outer membrane asymmetry maintenance of Gram-negative bacteria by the phospholipid transporter MlaFEDB

The asymmetric phospholipid outer membrane (OM) of Gram-negative bacteria serves as the first line of defense against cytotoxic substances such as antibiotics. The Mla pathway is known to maintain the lipid asymmetry of the OM by transporting phospholipids between the inner and outer membranes. Six Mla proteins MlaFEDBCA are involved, with the ABC transporter MlaFEDB acts through a mechanism yet to be elucidated. Here we determine cryo-EM structures of MlaFEDB in apo, phospholipid-, ADP- or AMP-PNP-bound state to 3.3-3.75 [A] resolution and establish a proteoliposome-based transport system containing MlaFEDB, MlaC and MlaA/OmpF to reveal the transport direction of phospholipids. Mutagenetic in vitro transport assays and in vivo sensitivity assays reveal functional residues which recognize and transport phospholipids as well as regulate the activity and structural stability of the MlaFEDB complex. Our work provides molecular basis for understanding the mechanism of the Mla pathway which could be targeted for antimicrobial drug development.

biochemistry↗

bioRxiv2020

Schisandrin B for treatment of male infertility

The decline of male fertility and its consequences on human populations are important public-health issues. However, there are limited choices for treatment of male infertility. In an attempt to identify a compound that could promote male fertility, we identified and characterized a library of small molecules from an ancient formulation Wuzi Yanzong-Pill, which was used as a folk medicine since the Tang dynasty of China. We found that SB enabled evident repairs in oligoasthenospermia-associated testicular tissue abnormality and in spermatogenesis disruption, resulting in significant improvements of sperm count, mobility, and reproductive ability in oligoasthenospermia mice. Furthermore, SB could alter substantial testicular genes (2033), among which, upregulation of Fst while downregulation of Inhba involved in reproductive signaling pathway could explain its role in enhancing spermatogenesis. The encouraging preclinical data with pharmacokinetics warranted a rapid development of this new class of therapeutic agent. Our finding provides a strong potent drug for treatment of male infertility.

pharmacology and toxicology↗

bioRxiv2019

MACS: Rapid aqueous clearing system for three-dimensional mapping of intact organs

Tissue optical clearing techniques have provided important tools for large-volume imaging. Aqueous-based clearing methods are known for good fluorescence preservation and scalable size maintenance, but are limited by either long incubation time, or insufficient clearing performance, or requirements for specialized devices. Additionally, due to the use of high concentration organic solvents or detergents, few clearing methods are compatible with lipophilic dyes while maintaining high clearing performance. To address these issues, we developed a rapid, highly efficient aqueous clearing method with robust compatibility, termed m-xylylenediamine (MXDA)-based Aqueous Clearing System (MACS). MACS can render intact organs highly transparent in a fairly short time and possesses ideal compatibility with multiple probes, especially for lipophilic dyes. Using MACS, we cleared the adult mouse brains within only 2.5 days for three-dimensional (3D) imaging of the neural structures labelled by various techniques. Combining MACS with DiI labelling, we visualized the vascular structures of various organs. MACS provides a useful tool for 3D mapping of intact tissues and is expected to facilitate morphological, physiological and pathological studies of various organs.

bioengineering↗