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Salt stress is a major environmental abiotic stress factor. Plants sense salt from germination onwards, negatively affecting their growth and development. Enhancing salt tolerance in crops at the sprout stage is crucial, given that it is the first stage to encounter stress. Melatonin (N-acetyl-5-methoxytryptamine) is a potent antioxidant that can alleviate stress from various environmental factors. Here, a common bean variety “Heiyundou” was used as the plant material. A concentration of 70 mMol·L−1 NaCl was chosen as the stress treatment, and 100 μmol·L−1 melatonin was applied. Four treatment groups were established: CK (control, water treatment), S (salt stress), M (melatonin), and M+S (salt stress with melatonin). Melatonin application under salt stress (M+S) significantly improved sprout length, surface area, volume, and average diameter compared to the salt stress group (S). Physiological analysis revealed that salt stress increased the activity of reactive oxygen species (ROS) scavenging enzymes, while exogenous melatonin (M+S) further enhanced this activity. Salt stress also significantly elevated levels of stress markers like malondialdehyde (MDA), hydrogen peroxide (H2O2), and superoxide anion (O2−). However, these markers decreased under the M+S treatment, indicating melatonin's protective effect. RNA sequencing (RNA-Seq) analysis identified 639 differentially expressed genes (DEGs) between the control (W) and salt stress (S) groups, and 170 DEGs between the salt stress (S) and salt stress with melatonin (M+S) groups. 40 DEGs were common to both comparisons (Co-DEGs). Gene Ontology (GO) enrichment analysis revealed that oxidoreductase activity (GO:0016491) and oxidation–reduction processes (GO:0055114) were enriched in all three groups (WvsS, SvsM+S, and Co-DEGs). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that phenylpropanoid biosynthesis (Ko00940) was the most enriched pathway in all three groups. Within this pathway, 4-coumarate-CoA ligase (4CL) and peroxidase (POD) were identified as key enzymes. Molecular docking simulations further confirmed the binding potential of melatonin to these two enzymes. Additionally, 4CL activity and lignin content analyses supported the role of phenylpropanoid biosynthesis as the underlying mechanism of melatonin's protective action. Collectively, these findings provide a theoretical basis for applying melatonin in enhancing salt tolerance in common bean crops.

Abstract Radiation triage and biological dosimetry are critical for the medical management of massive potentially exposed individuals following radiological accidents. Here, we performed a genome-wide screening of radiation-responding mRNAs, whose N6-methyladenosine (m6A) levels showed significant alteration after acute irradiation. The m6A levels of three genes, Ncoa4, Ate1 and Fgf22, in peripheral blood mononuclear cells (PBMCs) of mice showed excellent dose-response relationships and could serve as biomarkers of radiation exposure. Especially, the RNA m6A of Ncoa4 maintained a high level as long as 28 days after irradiation. We demonstrated its responsive specificity to radiation, conservation across the mice, monkeys and humans, and the dose-response relationship in PBMCs from cancer patients receiving radiation therapy. Finally, NOCA4 m6A-based biodosimetric models were constructed for estimating absorbed radiation doses in mice or humans. Collectively, this study demonstrated the potential feasibility of RNA m6A in radiation accidents management and clinical applications.

【Objective】 Improving irrigation water use efficiency is critical to developing water-saving agriculture. The aim of this paper is to present and validate a model to comprehensively evaluate irrigation water use efficiency. 【Method】 The model is based on the entropy-weighted technique for order of preference by similarity to ideal solution (TOPSIS), using the evaluation indexes constructed from irrigation water efficiency. We then applied it to evaluate water use efficiency from 2017 to 2020 in six irrigation areas in the Second Division of Xinjiang Production and Construction Corps. 【Result】 The results calculated from the model are consistent with the ground-truth data. The rank of the results calculated from the model is closely correlated with the rank of the effective utilization coefficient of the irrigation water and the rank of the results calculated from the AHP-fuzzy comprehensive evaluation (P

The identification of marine alkenones and anomalously high carbonate carbon isotopic values in sediments suggest the Qaidam Basin in the northern Tibetan Plateau was uplifted from sea level to its present altitude since the Mid-Miocene.

Summary: Fossil genera with similar features to the winged fruits of the living Engelhardia Lesch. ex Blume (e.g., Palaeocarya G. Saporta) have been widely reported in Cenozoic fossil floras of the Northern Hemisphere. However, fossil winged fruits of Engelhardia with detailed anatomical structures have only been found in the upper Eocene of North America. This study reports the first Engelhardia fossil winged fruits with detailed anatomical structures in East Asia from the Miocene Erzitang Formation of Guangxi, South China. The anatomical and morphological features of the new fossils, including the unique structure of secondary septa, clearly distinguish them from other fossil genera and show unambiguously their attribution to the genus Engelhardia. This discovery suggests that Engelhardia had reached its modern distribution during the Miocene and the climate of the Guiping Basin in Guangxi during the Miocene was similar to that of present-day tropical and subtropical regions in Asia.

The immune cell constituents and localisation within human hepatocellular carcinoma is not fully understood. Here the authors use single cell RNA sequencing of HCC from four different tissue sites and show differences between primary and metastatic tumours, tumour associated macrophages and immune cell populations.

Population-scale studies of structural variation (SV) are growing rapidly worldwide with the development of long-read sequencing technology, yielding a considerable number of novel SVs and complete gap-closed genome assemblies. Herein, we highlight recent studies using a hybrid sequencing strategy and present the challenges toward large-scale genotyping for SVs due to the reference bias. Genotyping SVs at a population scale remains challenging, which severely impacts genotype-based population genetic studies or genome-wide association studies of complex diseases. We summarize academic efforts to improve genotype quality through linear or graph representations of reference and alternative alleles. Graph-based genotypers capable of integrating diverse genetic information are effectively applied to large and diverse cohorts, contributing to unbiased downstream analysis. Meanwhile, there is still an urgent need in this field for efficient tools to construct complex graphs and perform sequence-to-graph alignments.

Single-cell transcriptomics offers opportunities to investigate ligand-receptor (LR) interactions between heterogeneous cell populations within tissues. However, most existing tools for the inference of intercellular communication do not allow prioritization of functional LR associations that provoke certain biological responses in the receiver cells. In addition, current tools do not enable the identification of the impact on the downstream cell types of the receiver cells. We present CommPath, an open-source R package and webserver, to analyze and visualize the LR interactions and pathway-mediated intercellular communication chain with single-cell transcriptomic data. CommPath curates a comprehensive signaling pathway database to interpret the consequences of LR associations and therefore infers functional LR interactions. Furthermore, CommPath determines cell-cell communication chain by considering both the upstream and downstream cells of user-defined cell populations. Applying CommPath to human hepatocellular carcinoma dataset shows its ability to decipher complex LR interaction patterns and the associated intercellular communication chain, as well as their changes in disease versus homeostasis.

For hematopoietic stem and progenitor cells (HSPCs), hypoxia is a specific microenvironment known as the hypoxic niche. How hypoxia regulates erythroid differentiation of HSPCs remains unclear. In this study, we show that hypoxia evidently accelerates erythroid differentiation, and autophagy plays a pivotal role in this process. We further determine that mTORC1 signaling is suppressed by hypoxia to relieve its inhibition of autophagy, and with the process of erythroid differentiation, mTORC1 activity gradually decreases and autophagy activity increases accordingly. Moreover, we provide evidence that the HIF-1 target gene REDD1 is upregulated to suppress mTORC1 signaling and enhance autophagy, thereby promoting erythroid differentiation under hypoxia. Together, our study identifies that the enhanced autophagy by hypoxia favors erythroid maturation and elucidates a new regulatory pattern whereby autophagy is progressively increased during erythroid differentiation, which is driven by the HIF-1/REDD1/mTORC1 signaling in a hypoxic niche.

Background and AimsRadiation-induced lung injury (RILI) is the most common complication associated with chest tumors, such as lung and breast cancers, after radiotherapy; however, the pathogenic mechanisms are unclear. Single-cell RNA sequencing has laid the foundation for studying RILI at the cellular microenvironmental level. This study focused on changes during the acute pneumonitis stage of RILI at the cellular microenvironmental level and investigated the interactions between different cell types.MethodsAn acute RILI model in mice and a single-cell transcriptional library were established. Intercellular communication networks were constructed to study the heterogeneity and intercellular interactions among different cell types.ResultsA single-cell transcriptome map was established in a mouse model of acute lung injury. In total, 18,500 single-cell transcripts were generated, and 10 major cell types were identified. The heterogeneity and radiosensitivity of each cell type or subtype in the lung tissues during the acute stage were revealed. It was found that immune cells had higher radiosensitivity than stromal cells. Immune cells were highly heterogeneous in terms of radiosensitivity, while some immune cells had the characteristics of radiation resistance. Two groups of radiation-induced Cd8+Mki67+ T cells and Cd4+Cxcr6+ helper T cells were identified. The presence of these cells was verified using immunofluorescence. The ligand-receptor interactions were analyzed by constructing intercellular communication networks. These explained the origins of the cells and revealed that they had been recruited from endothelial cells to the inflammatory site.ConclusionsThis study revealed the heterogeneity of in vivo radiosensitivity of different cell types in the lung at the initial stage post irradiation

Abstract Background Structural variation (SV) acts as an essential mutational force shaping the evolution and function of the human genome. However, few studies have examined the role of SVs in high-altitude adaptation and little is known of adaptive introgressed SVs in Tibetans so far. Results Here, we generate a comprehensive catalog of SVs in a Chinese Tibetan (n = 15) and Han (n = 10) population using nanopore sequencing technology. Among a total of 38,216 unique SVs in the catalog, 27% are sequence-resolved for the first time. We systematically assess the distribution of these SVs across repeat sequences and functional genomic regions. Through genotyping in additional 276 genomes, we identify 69 Tibetan-Han stratified SVs and 80 candidate adaptive genes. We also discover a few adaptive introgressed SV candidates and provide evidence for a deletion of 335 base pairs at 1p36.32. Conclusions Overall, our results highlight the important role of SVs in the evolutionary processes of Tibetans’ adaptation to the Qinghai-Tibet Plateau and provide a valuable resource for future high-altitude adaptation studies.

Radiation-induced brain injury (RIBI) is one of the most common and fatal complications of cranial radiation therapy (CRT); however, no effective intervention is available currently. Metformin has been reported to have anti-RIBI activity as a first-line anti-diabetic drug. However, the mechanism of action is unclear. An RIBI mice model and an in vitro cell model under 30 and 10 Gy 60Co γ-rays exposure were established to investigate the mechanism of metformin in RIBI. The results showed that pre-treatment with metformin protects hippocampal neurogenesis in the brain of mice and improves learning and memory ability after irradiation. Further investigations revealed that metformin pretreatment reduces inflammation and decreases DNA damage in the in vitro BV2 cell line. In addition, we observed that metformin inhibits the activation of IκB and IRF-3, which are downstream components of the cGAS-STING pathway. These findings suggest that metformin might protect the brain from RIBI, at least partly, through the cGAS pathway, making it a potential therapeutic drug for RIBI.

Summary: Objective: Kissing stent (KS) technique has been used as an alternative to aortic bifurcated bypass surgery (ABBS) for aortoiliac occlusive disease (AIOD). We aimed to compare the results of ABBS and KS in AIOD. Methods: Medical records of patients treated with ABBS and KS between March 2011 and December 2016 in a single center were retrospectively analyzed. The patients' characteristics and clinical outcomes were evaluated. Results: Patients who underwent ABBS had a more common history of smoking (P = 0.04) and lower body mass index (P = 0.02). A significant difference was observed between the two groups in terms of the TransAtlantic Inter-Society Consensus II classification (P

Knowledge of paleolake evolution is highly important for understanding the past hydroclimate regime on the Tibetan Plateau and associated forcing mechanisms. However, the hydrological history of paleolakes on the central plateau, the core region of the plateau, remains largely inconclusive. Here we present new biomarker records from lacustrine deposits of the Lunpori section in the Lunpola Basin to reconstruct detailed lake-level fluctuations during the mid-Miocene. A set of n-alkane indexes, including the proportion of aquatic macrophytes (Paq), average chain length and carbon preference index as well as the content of n-alkanes, vary substantially and consistently throughout the studied interval. Our results altogether show relatively low lake level at ∼16.3–15.5 Ma and high lake level before and after the interval, which is in line with the lithological observations in the section. Further comparison with existing regional and global temperature records suggests that lake level fluctuations can be largely linked to global climatic conditions during the mid-Miocene, with lake expansion during relatively warm periods and vice versa. Therefore, we infer that global climatic changes might have controlled the lake-level fluctuations in this region during the mid-Miocene, whereas the tectonic uplift likely played a subordinate role on this timescale.

Ceratophyllum L. is a cosmopolitan genus of perennial aquatic herbs that occur in quiet freshwaters. Fossils of this genus have been widely reported from the Northern Hemisphere, most of them occurring in the temperate zone. Here, we describe two species of fossil fruits discovered from subtropical areas of China. The fossil fruit discovered from the upper Eocene Huangniuling Formation of the Maoming Basin is designated as C. cf. muricatum Chamisso, and fruits discovered from the Miocene Erzitang Formation of the Guiping Basin are assigned to the extant species C. demersum L. The discovery of these two fossil species indicates that Ceratophyllum had spread to South China by the late Eocene and their distribution expanded in subtropical China during the Miocene.

Both Trapa L. and the extinct Hemitrapa Miki are aquatic plants in the family Lythraceae, with abundant fossil records in Eurasia and North America in the Cenozoic. However, documented materials are mainly based on fruit and pollen grains without reliable leaf fossils. Here, we report fossil leaves, fruit, and roots of Trapa and fruit of Hemitrapa from the late Eocene of Weinan, the Weihe Basin of central China. The fossil leaves are identified as a new species, Trapa natanifolia Z. C. Han et H. Jia sp. nov., which represents the earliest known record of a Trapa leaf fossil. It is remarkably similar to extant species of Trapa, mostly due to the unique inflated petiole structures found in both of them. While displaying prominent intergeneric differences, the incomplete fossil fruits are assigned to Trapa sp. indet. and Hemitrapa sp. indet. The former is the earliest fossil fruit record of Trapa, and the latter represents the earliest fossil record of Hemitrapa found in Asia. These new fossil discoveries suggest that the divergence of Trapa and Hemitrapa occurred at least by the late Eocene. It is believed that modern Trapa most likely originated in China. Furthermore, this unexpected aquatic plant fossil assemblage indicates that central China was warm and humid, with freshwater ponds or lakes, in the late Eocene and not as arid as previously thought.

Fokienia A. Henry & H. H. Thomas is a monotypic genus of the Cupressoideae Rich. ex Sweet (Cupressaceae), native to subtropical evergreen mesophytic forests in South China, northern Laos and Vietnam. The fossil record of Fokienia is very scanty, with only one known occurrence of foliage in the Oligocene of Longjing, Jilin, China. Here we report the fossil foliage of Fokienia discovered in the Miocene Erzitang Formation of the Guiping Basin, South China, which is similar to that of the only extant species Fokienia hodginsii in both macromorphological and epidermal features. This species is the earliest fossil record within the modern distribution area of Fokienia and the only fossil species for which morphology and anatomy have been studied in detail. Fossil evidence suggests that the genus Fokienia was present at middle latitudes of the Northern Hemisphere in the Oligocene and spread to South China during the Miocene. Due to physiological adaptations to warm-wet environments and weak cold tolerance, Fokienia migrated southward, as global climate cooling gradually drove it to extinction in the mid-latitudes. The ecological niche of the extant species, and co-existing plant fossils, suggest that the fossil assemblage represents the remains of an evergreen broad-leaved and conifer mixed forest growing under humid and warm Miocene climate.

Summary: Objective: Compared to the diameter measurement, volume measurement of the aneurysm can be an alternative option for accurate evaluation. This study was undertaken to analyze the relationship between the diameter and the volume measurement of the aorta after EVAR. Methods: From January 2012 to December 2016, 82 patients underwent EVAR in our institution. The infrarenal aorta after EVAR was evaluated with regard to maximal aortic diameter (DMAX) and aortic volume. The relationship between the DMAX and the aortic volume measurement after EVAR were analyzed. Results: The rate of enlargement of aortic volume with endoleak over time was 0.02 cm3/month. The rate of enlargement of DMAX with endoleak over time was 0.007 mm/month. The mean rate of enlargement of aortic volume was significantly different from the mean enlargement rate of DMAX (p = 0.02). A ≥12% of increase rate of aortic volume was equivalent to an increase of ≥5 mm in the DMAX after EVAR.Significantly more endoleak occurred in the DMAX-enlargement group than no-enlargement group (100% vs. 26.76%, p

The Neogene environment and paleovegetation of today’s semi-arid and arid Central Asia remain elusive. Little is known about the effect of paleoclimatic change on the distribution and ecological response mechanisms of aquatic plants, especially on the Tibetan Plateau. Here, we report a new species of Nelumbo Adanson, including leaves, receptacles, and fruits, namely Nelumbo delinghaensis sp. nov., from the Upper Youshashan Formation of the upper Middle Miocene in the northern Qaidam Basin on the Tibetan Plateau. The new species comprises centrally peltate leaves with 12–15 actinodromous primary veins and a receptacle embedded with ca. 15–30 fruits, with an unlobed central disc. Megafossils of lotus from northwest China broaden the geographical and stratigraphic ranges of Nelumbo. Our findings suggest that a large freshwater lake body surrounded by temperate forests and grassland developed in the Qaidam Basin during the late Middle Miocene, in sharp contrast to the present desert vegetation. The climate used to be sufficiently warm and moist enough to support a forest-steppe ecosystem with abundant freshwater bodies.

Knowledge about within-species variation in stomatal frequency with varying elevation at very high elevations is rare, which is crucial for us to understand how alpine plants are adapted to the extreme environment. Here, we focus on the variation in stomatal frequency in Kobresia royleana (Nees) Boeckeler (Cyperaceae, Cyperales) along two altitudinal transects (elevation ranges from 3723 m to 5081 m) in the center of the Tibetan Plateau. The result shows the stomatal density (SD) varied from 303 ± 55.6 mm−2 to 542 ± 81.8 mm−2, and stomatal index (SI) ranged from 21.0% to 29.6%. In contrast with most cases, an unexpected negative response of stomatal frequency to rising elevation was observed. Among abiotic factors, the growing season mean temperature and CO2 partial pressure significantly declined with increasing elevation, while the growing season precipitation did not vary. Therefore, the decreasing SD and SI were mainly due to the declining temperature rather than the decreasing CO2 partial pressure. Further, SD and SI were negatively related to leaf functional traits of specific leaf area (SLA), leaf nitrogen concentration (N) and stable carbon isotope ratios (δ13C), and all these morphological and physiological traits tended to covary with rising elevation and declining temperature. Meanwhile, the increasing δ13C, N and SLA with elevation seem to be strategies for alpine plants to cope with the low-temperature environments. Therefore, the observed covariance between stomatal frequency and leaf functional traits also suggests that the low temperature rather than low CO2 partial pressure mainly leads to the elevational pattern of stomatal frequency for this alpine species.

Hi-C is commonly used to study three-dimensional genome organization. However, due to the high sequencing cost and technical constraints, the resolution of most Hi-C datasets is coarse, resulting in a loss of information and biological interpretability. Here we develop DeepHiC, a generative adversarial network, to predict high-resolution Hi-C contact maps from low-coverage sequencing data. We demonstrated that DeepHiC is capable of reproducing high-resolution Hi-C data from as few as 1% downsampled reads. Empowered by adversarial training, our method can restore fine-grained details similar to those in high-resolution Hi-C matrices, boosting accuracy in chromatin loops identification and TADs detection, and outperforms the state-of-the-art methods in accuracy of prediction. Finally, application of DeepHiC to Hi-C data on mouse embryonic development can facilitate chromatin loop detection. We develop a web-based tool (DeepHiC, http://sysomics.com/deephic) that allows researchers to enhance their own Hi-C data with just a few clicks.

Abstract The genus Schima includes about 20 species and is distributed only in southern China and adjacent areas of Asia. The previous molecular phylogenetic analysis suggested Schima is in the tribe Gordoniae, along with Gordonia and Franklinia. However, because few fossils have been reported, the biogeographic origin of Schima is still poorly known. In this paper mummified fossil fruits of Schima are described from the upper Oligocene Yongning Formation of the Nanning Basin, Guangxi, South China. In gross morphology, the new fossil species, Schima kwangsiensis, is similar to the extant S. superba by its pentacarpellate, loculicidally dehiscent capsules, 5 imbricate sepals, pedicels with bracteoles and marginally winged seeds. Due to its excellent preservation, the new species may provide sufficient details for understanding the early evolutionary and phytogeographic history of the genus. Morphological clustering analysis shows that the new fossil species is closely related to two extant species (S. wallichii and S. superba) in the genus, implying that they may belong to an ancient taxon that occurs earlier than the others. More importantly, this discovery represents the earliest record of this genus in Asia and it explicitly moves the fossil record back to the late Oligocene in this region.

We report a case of annular epidermolytic ichthyosis (AEI) resulting from de novo keratin 1 gene mutation. AEI is a rare autosomal dominantly inherited cornification disorder and is a distinct phenotypic variant of bullous congenital ichthyosiform erythroderma. Blisters and erosions in AEI are widespread; hence, initially, it is sometimes mistaken with epidermolysis bullosa, acrodermatitis enteropathica, and staphylococcal scalded skin syndrome. Genetic tests including next-generation sequencing and Sanger sequencing are essential for AEI diagnosis. AEI is treated symptomatically by wound dressing, prevention of infection, and the use of emollients, humectants, and keratolytic products; topical or systemic retinoids may also prove helpful.

Sensitivity analysis is an important way for us to know how the input parameters will affect the output of a system. Therefore, recently, there is an increased interest in developing sensitivity analysis methods in continuous-energy Monte Carlo Code due to the fact that Monte Carlo method can perform high-fidelity simulations of nuclear reactor. Previous studies mainly focused on developing sensitivity analysis method suitable for analyze eigenvalue. There are relatively few researches for performing sensitivity analysis of generalized response function by using continuous-energy Monte Carlo code. So, in this work, the differential operator method (DOM) has been investigated and implemented in continuous-energy Reactor Monte Carlo code (RMC) to perform sensitivity analysis of generalized response function in the form of ratios of reaction rate. The DOM implemented in RMC is based on the analog Monte Carlo transport mode and non-analog Monte Carlo transport mode. The correctness of the newly implemented method has been verified by comparing the results with those calculated by using the collision history-based method through the Jezeble and Flattop benchmark problems. In general, the results given by the DOM agree well with those obtained by the collision history-based method with an accuracy of 5%. Moreover, it is also shown that the non-analog Monte Carlo transport mode can obtain lower relative standard deviation of the sensitivity coefficients than the analog Monte Carlo transport mode.

Biometric recognition technology based on eye-movement dynamics has been in development for more than ten years. Different visual tasks, feature extraction and feature recognition methods are proposed to improve the performance of eye movement biometric system. However, the correct identification and verification rates, especially in long-term experiments, as well as the effects of visual tasks and eye trackers' temporal and spatial resolution are still the foremost considerations in eye movement biometrics. With a focus on these issues, we proposed a new visual searching task for eye movement data collection and a new class of eye movement features for biometric recognition. In order to demonstrate the improvement of this visual searching task being used in eye movement biometrics, three other eye movement feature extraction methods were also tested on our eye movement datasets. Compared with the original results, all three methods yielded better results as expected. In addition, the biometric performance of these four feature extraction methods was also compared using the equal error rate (EER) and Rank-1 identification rate (Rank-1 IR), and the texture features introduced in this paper were ultimately shown to offer some advantages with regard to long-term stability and robustness over time and spatial precision. Finally, the results of different combinations of these methods with a score-level fusion method indicated that multi-biometric methods perform better in most cases.

Mirror-normal letter discriminations are thought to require mental rotation in order to transform the rotated alphanumeric character into its canonical orientation. Moreover, out-of-plane rotation is likely to occur after in-plane rotation to fully normalize the mirror version before the final mirror-normal judgment. The so-called rotation-related negativity, which varies with orientation, is found in both ERPonset (averaged with respect to stimulus onset) and ERPRT (averaged with respect to response time), representing the involvement of mental rotation in both time windows. Additionally, the mean amplitude of ERPRT correlates with individual performance. We performed a comprehensive analysis of the mirror-normal differences in the early and late phases of mental rotation and deduced that out-of-plane rotation is more likely to occur in the late phase and interacts with both in-plane rotation and the decision-making process, as indicated by both behavioral and electrophysiological findings.

MicroRNAs (miRNAs) are a class of small, noncoding RNAs that act as key regulators in various physiological and pathological processes. However, the regulatory mechanisms for miRNAs in colorectal cancer remain largely unknown. Here, we found that miR-103 is up-regulated in colorectal cancer and its overexpression is closely associated with tumor proliferation and migration. In addition, repressing the expression of miR-103 apparently inhibits colorectal cancer cell proliferation and migration in vitro and HCT-116 xenograft tumor growth in vivo. Subsequent software analysis and dual-luciferase reporter assay identified two tumor suppressor genes DICER and PTEN as direct targets of miR-103, and up-regulation of DICER and PTEN obtained similar results to that occurred in the silencing of miR-103. In addition, restoration of DICER and PTEN can inhibit miR-103-induced colorectal cancer cell proliferation and migration. Our data collectively demonstrate that miR-103 is an oncogene miRNA that promotes colorectal cancer proliferation and migration through down-regulation of the tumor suppressor genes DICER and PTEN. Thus, miR-103 may represent a new potential diagnostic and therapeutic target for colorectal cancer treatment.

Abstract: Lipidomic profiling has been linked to the detection of cancers as dysregulation of lipid metabolism is closely associated with many disease states. Current work on chip‐based profiling has been limited and is largely hindered by issues associated with the chip's sophisticated fabrication processes. We report here the design and fabrication of a highly efficient microfluidic mixer/extractor by using three‐dimensional (3D) printing technology for on‐chip cell lysis/enrichment for lipidomic profiling with matrix‐assisted laser desorption/ionization mass spectrometry (MALDI‐MS). The platform consists of a micropillar mixer for flow‐through lysis and an on‐chip reservoir to separate phases where the lipid‐enriched layer was collected for subsequent MS analysis. The mass transfer between the two phases was simulated by a computational fluid dynamics study, and the efficiency in cell lysis in different extraction solvent systems was characterized by fluorescence microscopy. Results showed increased performance in extraction with the micropillar mixer as compared with the standard Bligh‐Dyer method. For lipid profiling of C. reinhardtii cells by MALDI‐MS, over 65 lipid species from the monogalactosyldiacylglycerol, digalactosyldiacylglycerol, diacylglyceryltrimethylhomo‐Ser, and triacylglycerol lipid families have been identified. The effect of organic solvents on extraction and lipid profiles was also investigated, and the results indicated that the extractant formula has a diverse impact on the collection of certain types of lipid species, presenting useful guidance for the system to be applied to targeted enrichment of lipids with specific cells. The microfluidic chips by the 3D printing technique reported here offer new platforms potentially for clinical lipidomics and can provide a novel avenue in disease diagnosis.