Genome evolution and initial breeding of the Triticeae grass Leymus chinensis dominating the Eurasian Steppe.

Leymus chinensis, a dominant perennial grass in the Eurasian Steppe, is well known for its remarkable adaptability and forage quality. Hardly any breeding has been done on the grass, limiting its potential in ecological restoration and forage productivity. To enable genetic improvement of the untapped, important species, we obtained a 7.85-Gb high-quality genome of L. chinensis with a particularly long contig N50 (318.49 Mb). Its allotetraploid genome is estimated to originate 5.29 million years ago (MYA) from a cross between the Ns-subgenome relating to Psathyrostachys and the unknown Xm-subgenome. Multiple bursts of transposons during 0.433-1.842 MYA after genome allopolyploidization, which involved predominantly the Tekay and Angela of LTR retrotransposons, contributed to its genome expansion and complexity. With the genome resource available, we successfully developed a genetic transformation system as well as the gene-editing pipeline in L. chinensis. We knocked out the monocot-specific miR528 using CRISPR/Cas9, resulting in the improvement of yield-related traits with increases in the tiller number and growth rate. Our research provides valuable genomic resources for Triticeae evolutionary studies and presents a conceptual framework illustrating the utilization of genomic information and genome editing to accelerate the improvement of wild L. chinensis with features such as polyploidization and self-incompatibility.

N-Doping CQDs as an Efficient Fluorescence Probe Based on Dynamic Quenching for Determination of Copper Ions and Alcohol Sensing in Baijiu.

To address an accurate detection of heavy metal ions in Baijiu production, a nitrogen-doping carbon quantum dots (N-CQDs) was prepared by hydrothermal method from citric acid and urea. The as-prepared N-CQDs had an average particle size of 2.74 nm, and a large number of functional groups (amino, carbonyl group, etc.) attached on its surface, which obtained a 9.6% of quantum yield (QY) with relatively high and stable fluorescence performance. As a fluorescent sensor, the fluorescence of N-CQDs at 380 nm excitation wavelength could be quenched quantitatively by adding Cu2+, due to the dynamic quenching of electron transfer caused by the binding of amine groups and Cu2+, which showed excellent sensitivity and selectivity to Cu2+ in the range of 0.5-5 µM with a detection limit (LOD) of 0.032 µM. In addition, the N-CQDs as well as could be applied to quantitative determine alcohol content in the range of 10-80 V/V% depending on the fluorescence enhancement. Upon the experiment, the fluorescent mechanism was studied by Molecular dynamics (MD) simulations, which demonstrated that solvent effect played an influential role on sensing alcohol content in Baijiu. Overall, the work provided a theoretically guide for the design of fluorescence sensors to monitor heavy metal ion in liquid drinks and sense alcohol content.

Psychometric properties of the Chinese version of the Quick Delay Questionnaire (C-QDQ) and ecological characteristics of reward-delay impulsivity of adults with ADHD.

BACKGROUND: The Quick Delay Questionnaire (QDQ) is a short questionnaire designed to assess delay-related difficulties in adults. This study aimed to examine the reliability and validity of the Chinese version of the QDQ (C-QDQ) in Chinese adults, and explore the ecological characteristics of delay-related impulsivity in Chinese adults with attention-deficit/hyperactivity disorder (ADHD). METHODS: Data was collected from 302 adults, including ADHD (n = 209) and healthy controls (HCs) (n = 93). All participants completed the C-QDQ. The convergent validity, internal consistency, retest reliability and confirmatory factor analysis (CFA) of the C-QDQ were analyzed. The correlations between C-QDQ and two laboratory measures of delay-related difficulties and Barratt Impulsiveness Scale-11 (BIS-11), the comparison of C-QDQ scores between ADHD subgroups and HCs were also analyzed. RESULTS: The Cronbach's α of C-QDQ was between 0.83 and 0.89. The intraclass correlation coefficient of C-QDQ was between 0.80 and 0.83. The results of CFA of C-QDQ favoured the original two-factor model (delay aversion and delay discounting). Significant positive associations were found between C-QDQ scores and BIS-11 total score and performance on the laboratory measure of delay-related difficulties. Participants with ADHD had higher C-QDQ scores than HCs, and female ADHD reported higher scores on delay discounting subscale than male. ADHD-combined type (ADHD-C) reported higher scores on delay aversion subscale than ADHD-inattention type (ADHD-I). CONCLUSION: The C-QDQ is a valid and reliable tool to measure delay-related responses that appears to have clinical utility. It can present the delay-related impulsivity of patients with ADHD. Compared to HCs, the level of reward-delay impulsivity was higher in ADHD.

Cumulative residual cholesterol predicts the risk of cardiovascular disease in the general population aged 45 years and older.

BACKGROUND: Numerous studies have affirmed a robust correlation between residual cholesterol (RC) and the occurrence of cardiovascular disease (CVD). However, the current body of literature fails to adequately address the link between alterations in RC and the occurrence of CVD. Existing studies have focused mainly on individual RC values. Hence, the primary objective of this study is to elucidate the association between the cumulative RC (Cum-RC) and the morbidity of CVD. METHODS: The changes in RC were categorized into a high-level fast-growth group (Class 1) and a low-level slow-growth group (Class 2) by K-means cluster analysis. To investigate the relationship between combined exposure to multiple lipids and CVD risk, a weighted quantile sum (WQS) regression analysis was employed. This analysis involved the calculation of weights for total cholesterol (TC), low-density lipoprotein (LDL), and high-density lipoprotein (HDL), which were used to effectively elucidate the RC. RESULTS: Among the cohort of 5,372 research participants, a considerable proportion of 45.94% consisted of males, with a median age of 58. In the three years of follow-up, 669 participants (12.45%) had CVD. Logistic regression analysis revealed that Class 2 individuals had a significantly reduced risk of developing CVD compared to Class 1. The probability of having CVD increased by 13% for every 1-unit increase in the Cum-RC according to the analysis of continuous variables. The restricted cubic spline (RCS) analysis showed that Cum-RC and CVD risk were linearly related (P for nonlinearity = 0.679). The WQS regression results showed a nonsignificant trend toward an association between the WQS index and CVD incidence but an overall positive trend, with the greatest contribution from TC (weight = 0.652), followed by LDL (weight = 0.348). CONCLUSION: Cum-RC was positively and strongly related to CVD risk, suggesting that in addition to focusing on traditional lipid markers, early intervention in patients with increased RC may further reduce the incidence of CVD.

Association between relative muscle strength and cardiovascular disease among middle-aged and older adults in China.

BACKGROUND: The association between sarcopenia and cardiovascular disease (CVD) is well known. However, the clinical diagnosis of sarcopenia is complex and not suitable for early clinical identification and prevention of CVD. Relative muscle strength (RMS) is a relatively quantitative and straightforward indicator, but its association with CVD remains unclear. Hence, the objective of this research was to investigate the correlation between RMS and CVD incidence. METHODS: This was a cross-sectional study, using data from the China Health and Retirement Longitudinal Study (CHARLS) in 2011. CVD events were assessed through self-reported physician diagnoses. The RMS was determined by dividing the maximum grip strength by the appendicular skeletal muscle mass (ASM). This study used multivariate logistic regression and restricted cubic spline (RCS) curves to explore the correlation between RMS and CVD incidence. Additionally, we conducted subgroup analyses to provide additional evidence supporting the association between the two variables. RESULTS: A total of 8,733 people were included in our study, with 1,152 (13.19%) CVD patients and 7,581 (86.81%) non-CVD patients. When the data were grouped according to quartiles (Q) of RMS, the inverse association between CVD and RMS remained statistically significant even after controlling for all potential confounding factors. Compared with participants in Q1 of RMS, the ORs (95% CIs) of CVD among those in Q2-Q4 were 0.99 (0.83, 1.17), 0.81 (0.67, 0.98), and 0.70 (0.57, 0.85), respectively. Moreover, the RCS results showed a negative linear correlation between the RMS and CVD incidence (P for nonlinearity = 0.555). Subgroup analysis revealed no significant interaction in any of the groups except for the sex group (P for interaction = 0.046). CONCLUSION: Our study indicated a stable negative correlation between RMS and CVD incidence. RMS is helpful for the early identification and prevention of CVD.

Betaine Alleviates High-Fat Diet Induced Excessive Lipid Deposition in Gibel Carp Hepatopancreas and L8824 Cells by Enhancing VLDL Secretion through HNF4α/MTTP Pathway.

Betaine, a methyl donor, plays a crucial role in lipid metabolism. Previous studies have shown that appropriate betaine supplementation in a high-fat diet reduces triglycerides (TG) of serum and hepatopancreas in fish. However, the underlying mechanism remains unclear. This study examined whether betaine can enhance the secretion of very low-density lipoprotein (VLDL) and sought to identify the specific mechanisms through which this enhancement occurs. A lipid accumulation model was established in gibel carp and L8824 cells using a high-fat diet and oleic acid, respectively. Different doses of betaine (1, 4, and 16 g/kg in the diet; 400 µmol in cell culture) were administered, and measurements were taken for lipid deposition, gene expression of HNF4α, MTTP, and ApoB, as well as the regulation of Mttp and Apob promoters by HNF4α. The results showed that betaine supplementation mitigated lipid droplet accumulation, TG levels, and VLDL production induced by the high-fat diet in gibel carp hepatopancreas and L8824 cells. Moreover, betaine not only increased VLDL content in the cell culture supernatant but also reversed the inhibitory effects of the high-fat diet on protein expression of MTTP, ApoB, and HNF4α in both gibel carp hepatopancreas and L8824 cells. Additionally, HNF4α exhibits transactivating activity on the promoter of Mttp in gibel carp. These findings suggest that betaine supplementation exerts its effects through the HNF4α/MTTP/ApoB pathway, promoting the assembly and secretion of VLDL and effectively reducing lipid accumulation in the hepatopancreas of farmed gibel carp fed a high-fat diet.

[Preparation and characterization of co-loaded indocyanine green and elemene nano-emulsion in situ gel and its effect on proliferation of breast cancer MCF-7 cells].

This study aims to prepare co-loaded indocyanine green(ICG) and elemene(ELE) nano-emulsion(NE) in situ gel(ICG-ELE-NE-gel) and evaluate its physicochemical properties and antitumor activity in vitro. ICG-ELE-NE-gel was prepared by aqueous phase titration and cold solution methods, followed by characterization of the morphology, particle size, corrosion, and photothermal conversion characteristics. The human breast cancer MCF-7 cells were taken as the model, combined with 808 nm laser irradia-tion. Cell inhibition rate test and cell uptake test were performed. ICG-ELE-NE was spherical and uniform in size. The average particle size and Zeta potential were(85.61±0.35) nm and(-21.4±0.6) mV, respectively. The encapsulation efficiency and drug loading rate were 98.51%±0.39% and 10.96%±0.24%, respectively. ICG-ELE-NE-gel had a good photothermal conversion effect and good photothermal stability. The dissolution of ICG-ELE-NE-gel had both temperature and pH-responsive characteristics. Compared with free ELE, ICG-ELE-NE-gel combined with near-infrared light irradiation significantly enhanced the inhibitory effect on MCF-7 cells and could be uptaken in large amounts by MCF-7 cells. ICG-ELE-NE-gel was successfully prepared, and its antitumor activity was enhanced after 808 nm laser irradiation.

Inactivation of RPX1 in Arabidopsis confers resistance to Plutella xylostella through the accumulation of the homoterpene DMNT.

The lepidopteran crop pest Plutella xylostella causes severe constraints on Brassica cultivation. Here, we report a novel role for RPX1 (resistance to P. xylostella) in resistance to this pest in Arabidopsis thaliana. The rpx1-1 mutant repels P. xylostella larvae, and feeding on the rpx1-1 mutant severely damages the peritrophic matrix structure in the midgut of the larvae, thereby negatively affecting larval growth and pupation. This resistance results from the accumulation of defence compounds, including the homoterpene (3E)-4,8-dimethyl-1,3,7-nonatriene (DMNT), due to the upregulation of PENTACYCLIC TRITERPENE SYNTHASE 1 (PEN1), which encodes a key DMNT biosynthetic enzyme. P. xylostella infestation and wounding induce RPX1 protein degradation, which may confer a rapid response to insect infestation. RPX1 inactivation and PEN1 overexpression are not associated with negative trade-offs for plant growth but have much higher seed production than the wild-type in the presence of P. xylostella infestation. This study offers a new strategy for plant molecular breeding against P. xylostella.

O-GlcNAcylation of TDP-43 suppresses proteinopathies and promotes TDP-43's mRNA splicing activity.

Pathological TDP-43 aggregation is characteristic of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD-TDP); however, how TDP-43 aggregation and function are regulated remain poorly understood. Here, we show that O-GlcNAc transferase OGT-mediated O-GlcNAcylation of TDP-43 suppresses ALS-associated proteinopathies and promotes TDP-43's splicing function. Biochemical and cell-based assays indicate that OGT's catalytic activity suppresses TDP-43 aggregation and hyperphosphorylation, whereas abolishment of TDP-43 O-GlcNAcylation impairs its RNA splicing activity. We further show that TDP-43 mutations in the O-GlcNAcylation sites improve locomotion defects of larvae and adult flies and extend adult life spans, following TDP-43 overexpression in Drosophila motor neurons. We finally demonstrate that O-GlcNAcylation of TDP-43 promotes proper splicing of many mRNAs, including STMN2, which is required for normal axonal outgrowth and regeneration. Our findings suggest that O-GlcNAcylation might be a target for the treatment of TDP-43-linked pathogenesis.

Low Cu(II) Concentration Detection Based on Fluorescent Detector Made from Citric Acid and Urea.

Carbon quantum dots (CQD) are an advanced fluorescent material, which has attracted more and more attention in theoretical research and practical applications. To obtain stable CQDs with high fluorescence characteristics for detecting trace metal ions in water, nitrogen-doped carbon quantum dots (N-CQDs) based fluorescent sensors were synthesized by the hydrothermal method, using citric acid and urea as source. Transmission electron microscopy (TEM) images showed that the synthesized N-CQDs maintained a narrow particle size distribution bellow 10 nm, and its average size was 3.07 nm. Fourier transform infrared spectroscopy (FT-IR) indicated that abundant hydroxyl and carboxyl functional groups existed on N-CQDs surface, which helped N-CQDs highly disperse in water. In addition, UV-vis spectroscopy and photoluminescence demonstrated that the N-CQDs obtained a 10.27% of quantum yield (QY) with relatively high and stable fluorescence performance. As a fluorescent sensor, the N-CQDs showed a fluorescence "ON-OFF" mechanism during the Cu2+ detection, which was induced from the electrons transition in surface functional groups. The final N-CQDs exhibited a wide linear relationship between fluorescence response and concentration of Cu2+ in range of 0.3-0.7 µM with a detection limit of 0.071 µM. Furthermore, the detection of Cu2+ in the simulating surface water (by adding interfering metal ions in purified water) and the tap water (from municipal water in Beijing) were used to verify N-CQDs practical application.

Biomimetic hypoxia-triggered RNAi nanomedicine for synergistically mediating chemo/radiotherapy of glioblastoma.

Although RNA interference (RNAi) therapy has emerged as a potential tool in cancer therapeutics, the application of RNAi to glioblastoma (GBM) remains a hurdle. Herein, to improve the therapeutic effect of RNAi on GBM, a cancer cell membrane (CCM)-disguised hypoxia-triggered RNAi nanomedicine was developed for short interfering RNA (siRNA) delivery to sensitize cells to chemotherapy and radiotherapy. Our synthesized CCM-disguised RNAi nanomedicine showed prolonged blood circulation, high BBB transcytosis and specific accumulation in GBM sites via homotypic recognition. Disruption and effective anti-GBM agents were triggered in the hypoxic region, leading to efficient tumor suppression by using phosphoglycerate kinase 1 (PGK1) silencing to enhance paclitaxel-induced chemotherapy and sensitize hypoxic GBM cells to ionizing radiation. In summary, a biomimetic intelligent RNAi nanomedicine has been developed for siRNA delivery to synergistically mediate a combined chemo/radiotherapy that presents immune-free and hypoxia-triggered properties with high survival rates for orthotopic GBM treatment.

The effect of aerobic exercise on oxidative stress in patients with chronic kidney disease: a systematic review and meta-analysis with trial sequential analysis.

PURPOSE: The purpose of this study was to investigate how aerobic exercise affects oxidative stress (OS) in patients with chronic kidney disease (CKD). METHODS: Retrieval dates range from the date the database was established to 19 July 2023, without languages being restricted. A meta-analysis and sensitivity analysis were conducted using RevMan 5.3 and Stata 16.0. RESULTS: The meta-analysis showed that, compared to usual activity or no exercise, aerobic exercise significantly reduced the oxidative markers malondialdehyde (MDA) (mean differences (MD) - 0.96 (95% CI -1.33, - 0.59); p < 0.00001), advanced oxidation protein product (AOPP) (MD - 3.49 (95% CI - 5.05, - 1.93); p < 0.00001), F2-isoprostanes (F2-iso) (MD - 11.02 (95% CI - 17.79, - 4.25); p = 0.001). Aerobic exercise also increased the antioxidant marker superoxide dismutase (SOD) in CKD patients (standardized mean differences (SMD) 1.30 (95% CI 0.56, 2.04); p = 0.0005). Subgroup analysis showed a significant increase in glutathione peroxidase (GPX) in patients aged ≥60 years (SMD 2.11 (95% CI 1.69, 2.54); p < 0.00001). The change in total antioxidant capacity (TAC) after aerobic exercise was insignificant in patients with CKD. The trial sequential analysis supported aerobic exercise's effectiveness in improving MDA, SOD, AOPP, and F2-iso in patients with CKD. CONCLUSION: The results of this review suggest that aerobic exercise improves OS indicators (MDA, SOD, AOPP, and F2-iso) in CKD patients compared to conventional treatment or no exercise and that the effects on GPX and TAC indicators need further confirmation. For better validation of benefits and exploration of the best aerobic exercise regimen to improve OS status with CKD, further studies with high methodological quality and large sample sizes are needed.

Efficient CRISPR/Cas9-mediated genome editing in sheepgrass (Leymus chinensis).

The lack of genome editing platforms has hampered efforts to study and improve forage crops that can be grown on lands not suited to other crops. Here, we established efficient Agrobacterium-mediated clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated nuclease 9 (Cas9) genome editing in a perennial, stress-tolerant forage grass, sheepgrass (Leymus chinensis). By screening for active single-guide RNAs (sgRNAs), accessions that regenerate well, suitable Agrobacterium strains, and optimal culture media, and co-expressing the morphogenic factor TaWOX5, we achieved 11% transformation and 5.83% editing efficiency in sheepgrass. Knocking out Teosinte Branched1 (TB1) significantly increased tiller number and biomass. This study opens avenues for studying gene function and breeding in sheepgrass.

Efficacy of cognitive behavioural therapy in medicated adults with attention-deficit/hyperactivity disorder in multiple dimensions: a randomised controlled trial.

The study aimed to evaluate the efficacy of group cognitive behavioural therapy (CBT) in medicated adults with attention-deficit/hyperactivity disorder (ADHD) with a multidimensional evaluation and follow-up to week 36. Ninety-eight adult ADHD were randomly allocated to the CBT combined with medication (CBT + M) group or the medication (M) only group. The primary endpoint was the ADHD-Rating Scale (ADHD-RS). Secondary endpoints included emotional symptoms, self-esteem, automatic thoughts, quality of life (QoL), and executive function (EF). The outcome measures were obtained at baseline (T1), after the 12-week CBT treatment (T2), and at two follow-up time points (week 24, T3, and week 36, T4). Compared to the M-only group, the patients in the CBT + M group showed an overall significantly greater reduction from baseline in ADHD core symptoms (ADHD-RS total score at T3, and inattention subscale at T2 and T3), depression and anxiety symptoms (T2-T4), state anxiety (T2 and T3) and trait anxiety (T2), automatic thoughts questionnaire at T3, and QoL (physical domain, psychological domain, and social domain, most significant at T3 and weakened at T4). These findings further confirmed the efficacy of CBT on multiple dimensions and verified improvements in automatic thinking in adult ADHD. The superiority of the combination treatment mainly manifested in reduced inattention, emotional symptoms, and maladaptive thoughts and improved QoL. Trial registration number ChiCTR1900021705 (March-05-2019).

Mesenchymal stem cells in cancer progression and anticancer therapeutic resistance.

Increasing evidence indicates that the tumor microenvironment appears to play an increasingly important role in cancer progression and therapeutic resistance. Several types of cells within the tumor stroma had distinct impacts on cancer progression, either promoting or inhibiting cancer cell growth. Mesenchymal stem cells (MSCs) are a distinct type of cells that is linked to tumor development. MSCs are recognized for homing to tumor locations and promoting or inhibiting cancer cell proliferation, angiogenesis and metastasis. Moreover, emerging studies suggests that MSCs are also involved in therapeutic resistance. In this review, we analyzed the existing researches and elaborate on the functions of MSCs in cancer progression and anticancer therapeutic resistance, demonstrating that MSCs may be a viable cancer therapeutic target.

Trace Fe Incorporation into Ni-(oxy)hydroxide Stabilizes Ni3+ Sites for Anodic Oxygen Evolution: A Double Thin-Layer Study.

Iron incorporation is essential for the record activity of NiFe-(oxy)hydroxides to oxygen evolution reaction (OER), but the details of how Fe affects catalysis remain under active investigation. In this work, we present a double thin-layer strategy for finding unique and solid evidence for the role of Fe in the OER mechanism. A thin-layer catalyst of a few nanometers of thickness was deposited on a Ni substrate and a thin-layer electrolyte of 0.1 mm thickness was created using a thin-layer spectroelectrochemical cell. The OER activity, the catalyst composition, and the electrolyte species were investigated together as a function of the Fe deposition time. The results show that trace Fe incorporation favors the formation of ß-NiOOH in the thin-layer catalyst and effectively suppresses the dissolution of NiOOH into the electrolyte. The results of double-potential step chronoabsorptometry and cyclic voltabsorptometry demonstrate the potential-dependent formation of a Ni3+ intermediate in the electrolyte and, more importantly, the dissolution suppression effect due to Fe incorporation. These findings link the role of Fe in OER catalysis to the increased insolubility of Ni3+ active sites and highlight the importance of paying close attention to the active-site stability of an electrocatalyst impaired by the electrolyte at a reaction potential.

The ABA-induced soybean ERF transcription factor gene GmERF75 plays a role in enhancing osmotic stress tolerance in Arabidopsis and soybean.

BACKGROUND: Ethylene-responsive factors (ERFs) play important roles in plant growth and development and the response to adverse environmental factors, including abiotic and biotic stresses. RESULTS: In the present study, we identified 160 soybean ERF genes distributed across 20 chromosomes that could be clustered into eight groups based on phylogenetic relationships. A highly ABA-responsive ERF gene, GmERF75, belonging to Group VII was further characterized. Subcellular localization analysis showed that the GmERF75 protein is localized in the nucleus, and qRT-PCR results showed that GmERF75 is responsive to multiple abiotic stresses and exogenous hormones. GmERF75-overexpressing Arabidopsis lines showed higher chlorophyll content compared to WT and mutants under osmotic stress. Two independent Arabidopsis mutations of AtERF71, a gene homologous to GmERF75, displayed shorter hypocotyls, and overexpression of GmERF75 in these mutants could rescue the short hypocotyl phenotypes. Overexpressing GmERF75 in soybean hairy roots improved root growth under exogenous ABA and salt stress. CONCLUSIONS: These results suggested that GmERF75 is an important plant transcription factor that plays a critical role in enhancing osmotic tolerance in both Arabidopsis and soybean.

Proteomics Analysis to Identify Proteins and Pathways Associated with the Novel Lesion Mimic Mutant E40 in Rice Using iTRAQ-Based Strategy.

A novel rice lesion mimic mutant (LMM) was isolated from the mutant population of Japonica rice cultivar Hitomebore generated by ethyl methane sulfonate (EMS) treatment. Compared with the wild-type (WT), the mutant, tentatively designated E40, developed necrotic lesions over the whole growth period along with detectable changes in several important agronomic traits including lower height, fewer tillers, lower yield, and premature death. To understand the molecular mechanism of mutation-induced phenotypic differences in E40, a proteomics-based approach was used to identify differentially accumulated proteins between E40 and WT. Proteomic data from isobaric tags for relative and absolute quantitation (iTRAQ) showed that 233 proteins were significantly up- or down-regulated in E40 compared with WT. These proteins are involved in diverse biological processes, but phenylpropanoid biosynthesis was the only up-regulated pathway. Differential expression of the genes encoding some candidate proteins with significant up- or down-regulation in E40 were further verified by qPCR. Consistent with the proteomic results, substance and energy flow in E40 shifted from basic metabolism to secondary metabolism, mainly phenylpropanoid biosynthesis, which is likely involved in the formation of leaf spots.

Cell cycle-dependent degradation of the methyltransferase SETD3 attenuates cell proliferation and liver tumorigenesis.

Histone modifications, including lysine methylation, are epigenetic marks that influence many biological pathways. Accordingly, many methyltransferases have critical roles in various biological processes, and their dysregulation is often associated with cancer. However, the biological functions and regulation of many methyltransferases are unclear. Here, we report that a human homolog of the methyltransferase SET (SU(var), enhancer of zeste, and trithorax) domain containing 3 (SETD3) is cell cycle-regulated; SETD3 protein levels peaked in S phase and were lowest in M phase. We found that the ß-isoform of the tumor suppressor F-box and WD repeat domain containing 7 (FBXW7ß) specifically mediates SETD3 degradation. Aligning the SETD3 sequence with those of well known FBXW7 substrates, we identified six potential non-canonical Cdc4 phosphodegrons (CPDs), and one of them, CPD1, is primarily phosphorylated by the kinase glycogen synthase kinase 3 (GSK3ß), which is required for FBXW7ß-mediated recognition and degradation. Moreover, depletion or inhibition of GSK3ß or FBXW7ß resulted in elevated SETD3 levels. Mutations of the phosphorylated residues in CPD1 of SETD3 abolished the interaction between FBXW7ß and SETD3 and prevented SETD3 degradation. Our data further indicated that SETD3 levels positively correlated with cell proliferation of liver cancer cells and liver tumorigenesis in a xenograft mouse model, and that overexpression of FBXW7ß counteracts the SETD3's tumorigenic role. We also show that SETD3 levels correlate with cancer malignancy, indicated by SETD3 levels that the 54 liver tumors are 2-fold higher than those in the relevant adjacent tissues. Collectively, these data elucidated that a GSK3ß-FBXW7ß-dependent mechanism controls SETD3 protein levels during the cell cycle and attenuates its oncogenic role in liver tumorigenesis.

Identification and characterization of GmMYB118 responses to drought and salt stress.

BACKGROUND: Abiotic stress severely influences plant growth and development. MYB transcription factors (TFs), which compose one of the largest TF families, play an important role in abiotic stress responses. RESULT: We identified 139 soybean MYB-related genes; these genes were divided into six groups based on their conserved domain and were distributed among 20 chromosomes (Chrs). Quantitative real-time PCR (qRT-PCR) indicated that GmMYB118 highly responsive to drought, salt and high temperature stress; thus, this gene was selected for further analysis. Subcellular localization revealed that the GmMYB118 protein located in the nucleus. Ectopic expression (EX) of GmMYB118 increased tolerance to drought and salt stress and regulated the expression of several stress-associated genes in transgenic Arabidopsis plants. Similarly, GmMYB118-overexpressing (OE) soybean plants generated via Agrobacterium rhizogenes (A. rhizogenes)-mediated transformation of the hairy roots showed improved drought and salt tolerance. Furthermore, compared with the control (CK) plants, the clustered, regularly interspaced, short palindromic repeat (CRISPR)-transformed plants exhibited reduced drought and salt tolerance. The contents of proline and chlorophyll in the OE plants were significantly greater than those in the CK plants, whose contents were greater than those in the CRISPR plants under drought and salt stress conditions. In contrast, the reactive oxygen species (ROS) and malondialdehyde (MDA) contents were significantly lower in the OE plants than in the CK plants, whose contents were lower than those in the CRISPR plants under stress conditions. CONCLUSIONS: These results indicated that GmMYB118 could improve tolerance to drought and salt stress by promoting expression of stress-associated genes and regulating osmotic and oxidizing substances to maintain cell homeostasis.