Background Colorectal cancer (CRC) is one of the leading causes of tumor-related death worldwide, and its main cause of death is distant metastasis. Methyltransferase-like 14(METTL14), a major RNA N6-adenosine methyltransferase, is involved in tumor progression via regulating RNA function. The goal of the study is to uncover the biological function and molecular mechanism of METTL14 in CRC. Methods Quantitative real-time PCR (qRT-PCR), western blot and immunohistochemical (IHC) assays were employed to detect METTL14 and SOX4 in CRC cell lines and tissues. The biological functions of METTL14 were demonstrated using in vitro and in vivo experiments. Chromatin immunoprecipitation (ChIP), Transcrptomic RNA sequencing (RNA-Seq), m6A-RNA immunoprecipitation sequencing (MeRIP-Seq), RNA immunoprecipitation and luciferase reporter assays were used to explore the mechanism of METTL14 action. Results METTL14 expression was significantly downregulated in CRC and decreased METTL14 was associated with poor overall survival (OS). Both the univariate and multivariate Cox regression analysis indicated that METTL14 was an independent prognostic factor in CRC. Moreover, lysine-specific histone demethylase 5C(KDM5C)-mediated demethylation of histone H3 lysine 4 tri-methylation(H3K4me3) in the promoter of METTL14 inhibited METTL14 transcription. Functionally, we verified that METTL14 inhibited CRC cells migration, invasion and metastasis through in vitro and in vivo assays, respectively. Furthermore, we identified SRY-related high-mobility-group box 4(SOX4) as a target of METTL14-mediated m6A modification. Knockdown of METTL14 markedly abolished SOX4 mRNA m6A modification and elevated SOX4 mRNA expression. We also revealed that METTL14-mediated SOX4 mRNA degradation relied on the YTHDF2-dependent pathway. Lastly, we demonstrated that METTL14 might inhibit CRC malignant process partly through SOX4-mediated EMT process and PI3K/Akt signals. Conclusions Decreased METTL14 facilitates tumor metastasis in CRC, suggesting that METTL14 might be a potential prognostic biomarker and effective therapeutic target for CRC. Graphical abstract

In our study, the effects of water stress on photosynthesis and photosynthetic electron transport chain (PETC) were studied in several ways, including monitoring the change of gas exchange parameters, modulated chlorophyll fluorescence, rapid fluorescence induction kinetics, reactive oxygen species (ROS), antioxidant enzyme activities and D1 protein levels in apple leaves. Our results show that when leaf water potential (ψw) is above –1.5 MPa, the stomatal limitation should be the main reason for a drop of photosynthesis. In this period, photosynthetic rate (PN), stomatal conductance (Gs), transpiration rate (E) and intercellular CO2 concentration (Ci) all showed a strong positive correlation with ψw. Modulated chlorophyll fluorescence parameters related to photosynthetic biochemistry activity including maximum photochemical efficiency (Fv/Fm), actual photochemical efficiency of PSII (ΦPSII), photochemical quenching coefficient (qP) and coefficient of photochemical fluorescence quenching assuming interconnected PSII antennae (qL) also showed a strong positive correlation as ψw gradually decreased. On the other hand, in this period, Stern-Volmer type non-photochemical quenching coefficient (NPQ) and quantum yield of light-induced non-photochemical fluorescence quenching [Y(NPQ)] kept going up, which shows an attempt to dissipate excess energy to avoid damage to plants. When ψw was below –1.5 MPa, PN continued to decrease linearly, while Ci increased and a ‘V’ model presents the correlation between Ci and ψw by polynomial regression. This implies that, in this period, the drop in photosynthesis activity might be caused by non-stomatal limitation. Fv/Fm, ΦPSII, qP and qL in apple leaves treated with water stress were much lower than in control, while NPQ and Y(NPQ) started to go down. This demonstrates that excess energy might exceed the tolerance ability of apple leaves. Consistent with changes of these parameters, excess energy led to an increase in the production of ROS including H2O2 and O2•−. Although the activities of antioxidant enzymes like catalase (CAT), superoxide dismutase (SOD) and peroxidase (POD) increased dramatically and ascorbate peroxidase (APX) decreased in apple leaves with drought stress, it was still not sufficient to scavenge ROS. Consequently, the accumulation of ROS triggered a reduction of net D1 protein content, a core protein in the PSII reaction center. As D1 is responsible for the photosynthetic electron transport from plastoquinone A (QA) to plastoquinone B (QB), the capacity of PETC between QA and QB was considerably downregulated. The decline of photosynthesis and activity of PETC may result in the shortage of adenosine triphosphate (ATP) and limitation the regeneration of RuBP (Jmax), a key enzyme in CO2 assimilation. These are all non-stomatal factors and together contributed to decreased CO2 assimilation under severe water stress.

Long non-coding RNAs (lncRNAs) have been recently recognized as a major class of regulators in mammalian systems. 91H, a novel long noncoding antisense transcripts located on the position of the H19/IGF2 locus has been suggested to play a potential tumor-suppressor role in tumor development. However, little study has proved the mechanism in esophageal squamous cell carcinoma (ESCC). We carried out this study to explore the role of lncRNA 91H in the regulation of H19 imprinting control regions (ICR) and IGF2 expression and the association between 91H and ESCC progression. The cell line TE-1, Eca-109, and 232 ESCC patients' matched sets of paraffin-embedded adjacent normal and tumor samples were obtained in this study. The results showed that 91H expression was significantly lower in patients with higher depth of invasion, neoplastic grading and TNM which usually leads to the overexpression of IGF2 in tumor progression. The expression of 91H usually decreased in TE-1 and Eca-109 when treated with demethylation agent. Further analysis revealed that, in 91H knockdown cell lines, IGF2 expression was also significantly higher than negative controls. Therefore, the results demonstrated that the lncRNA 91H was associated with H19 ICR methylation and inhibited IGF2 expression of ESCC patients which may optimize the mechanism of IGF2 regulation in tumor development. Patients with higher depth of invasion, neoplastic grading and TNM usually demonstrated lower 91H expression potentially represent a novel clinically relevant event to identify individuals at increased risk for the occurrence, progression and prognosis of ESCC.

The thermal dissipation technique is widely used to estimate transpiration of individual trees and forest stands, but there are conflicting reports regarding its accuracy. We compared the rate of water uptake by stems of six tree species in potometers with sap flow (F S ) estimates derived from thermal dissipation sensors to evaluate the accuracy of the technique. To include the full range of xylem anatomies (i.e., diffuse-porous, ring-porous, and tracheid), we used saplings of sweetgum (Liquidambar styraciflua), eastern cottonwood (Populus deltoides), white oak (Quercus alba), American elm (Ulmus americana), shortleaf pine (Pinus echinata), and loblolly pine (Pinus taeda). In almost all instances, estimated F S deviated substantially from actual F S , with the discrepancy in cumulative F S ranging from 9 to 55%. The thermal dissipation technique generally underestimated F S . There were a number of potential causes of these errors, including species characteristics and probe construction and installation. Species with the same xylem anatomy generally did not show similar relationships between estimated and actual F S , and the largest errors were in species with diffuse-porous (Populus deltoides, 34%) and tracheid (Pinus taeda, 55%) xylem anatomies, rather than ring-porous species Quercus alba (9%) and Ulmus americana (15%) as we had predicted. New species-specific a and b parameter values only modestly improved the accuracy of F S estimates. However, the relationship between the estimated and actual F S was linear in all cases and a simple calibration based on the slope of this relationship reduced the error to 1-4% in five of the species, and to 8% in Liquidambar styraciflua. Our calibration approach compensated simultaneously for variation in species characteristics and sensor construction and use. We conclude that speciesspecific calibrations can substantially increase the accuracy of the thermal dissipation technique.

Background A severe form of pneumonia, named coronavirus disease 2019 (COVID-19) by the World Health Organization is widespread on the whole world. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was proved to be the main agent of COVID-19. In the present study, we conducted an in depth analysis of the SARS-COV-2 nucleocapsid to identify potential targets that may allow identification of therapeutic targets. Methods The SARS-COV-2 N protein subcellular localization and physicochemical property was analyzed by PSORT II Prediction and ProtParam tool. Then SOPMA tool and swiss-model was applied to analyze the structure of N protein. Next, the biological function was explored by mass spectrometry analysis and flow cytometry. At last, its potential phosphorylation sites were analyzed by NetPhos3.1 Server and PROVEAN PROTEIN. Results SARS-COV-2 N protein composed of 419 aa, is a 45.6 kDa positively charged unstable hydrophobic protein. It has 91 and 49% similarity to SARS-CoV and MERS-CoV and is predicted to be predominantly a nuclear protein. It mainly contains random coil (55.13%) of which the tertiary structure was further determined with high reliability (95.76%). Cells transfected with SARS-COV-2 N protein usually show a G1/S phase block company with an increased expression of TUBA1C, TUBB6. At last, our analysis of SARS-COV-2 N protein predicted a total number of 12 phosphorylated sites and 9 potential protein kinases which would significantly affect SARS-COV-2 N protein function. Conclusion In this study, we report the physicochemical properties, subcellular localization, and biological function of SARS-COV-2 N protein. The 12 phosphorylated sites and 9 potential protein kinase sites in SARS-COV-2 N protein may serve as promising targets for drug discovery and development for of a recombinant virus vaccine.

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With people's changing life style and dietary habits, the prevalence of type 2 diabetes mellitus (T2DM) has become much more serious than ever before. T2DM is a polygenic metabolic disorder, resulting from the interaction of genetic and various environmental factors. Among all the T2DM related genes, the transcription factor 7 like 2 (TCF7L2) gene is one of the most relevant risk-related genes for T2DM. However, the role of TCF7L2 in T2DM pathogenesis has not yet been interpreted thoroughly. Based on the experimental studies in recent years, this review discusses several possible mechanisms of T2DM pathogenesis induced by TCF7L2.

According to historical records, ethnic Hui in China obtained substantial genetic components from western Eurasian populations during their Islamization. However, some scholars believed that the ancestry of Hui people were native Chinese populations. In this context, the formation of Hui is due to simple cultural diffusion rather than demic diffusion. In this study, we examined the forensic and population genetic application of the 30 InDel loci in Hui population from Ningxia Hui Autonomous Region, Northwest China. Genotype analysis of 129 unrelated individuals revealed that all loci were in the Hardy–Weinberg equilibrium in Ningxia Hui. Forensic indices calculated from genotypes demonstrated that this panel, Qiagen DIPplex ® Investigator kit, was powerful enough to be used in individual identification but not in paternity cases. Through population genetic analysis, we found that Ningxia Hui received much more genetic contributions from East Asian populations than those from western Eurasian populations. Finally, we statistically identified the admixture signal of eastern and western Eurasians, although the latter is weak, in Ningxia Hui via the three-population test. All this evidence suggested that the formation of Ningxia Hui was mainly attributed to the cultural transformation of local Chinese residents with minor gene flow from western Eurasian populations.