MDSi: Multi-omics Database for Setaria italica.

BACKGROUND: Foxtail millet (Setaria italica) harbors the small diploid genome (~ 450 Mb) and shows the high inbreeding rate and close relationship to several major foods, feed, fuel and bioenergy grasses. Previously, we created a mini foxtail millet, xiaomi, with an Arabidopsis-like life cycle. The de novo assembled genome data with high-quality and an efficient Agrobacterium-mediated genetic transformation system made xiaomi an ideal C4 model system. The mini foxtail millet has been widely shared in the research community and as a result there is a growing need for a user-friendly portal and intuitive interface to perform exploratory analysis of the data. RESULTS: Here, we built a Multi-omics Database for Setaria italica (MDSi, http://sky.sxau.edu.cn/MDSi.htm ), that contains xiaomi genome of 161,844 annotations, 34,436 protein-coding genes and their expression information in 29 different tissues of xiaomi (6) and JG21 (23) samples that can be showed as an Electronic Fluorescent Pictograph (xEFP) in-situ. Moreover, the whole-genome resequencing (WGS) data of 398 germplasms, including 360 foxtail millets and 38 green foxtails and the corresponding metabolic data were available in MDSi. The SNPs and Indels of these germplasms were called in advance and can be searched and compared in an interactive manner. Common tools including BLAST, GBrowse, JBrowse, map viewer, and data downloads were implemented in MDSi. CONCLUSION: The MDSi constructed in this study integrated and visualized data from three levels of genomics, transcriptomics and metabolomics, and also provides information on the variation of hundreds of germplasm resources that can satisfies the mainstream requirements and supports the corresponding research community.

High glucose promotes the progression of colorectal cancer by activating the BMP4 signaling and inhibited by glucagon-like peptide-1 receptor agonist.

BACKGROUND: The detailed molecular mechanism between type 2 diabetes mellitus (T2DM) and colorectal cancer (CRC) is still uncertain. Bone morphogenetic protein 4 (BMP4) dysregulation is implicated in T2DM and CRC, respectively. This study aims to investigate whether BMP4 can mediate the interaction of CRC with T2DM. METHODS: We firstly explored the expression of BMP4 in The Cancer Genome Altas (TCGA) databases and CRC patients with or without DM from the Shanghai Tenth People's Hospital. The diabetic model of CRC cell lines in vitro and the mice model in vivo were developed to explore the BMP4 expression during CRC with or without diabetes. Further inhibition of BMP4 to observe its effects on CRC. Also, glucagon-like peptide-1 receptor agonist (GLP-1RA) was used to verify the underlying mechanism of hypoglycemic drugs on CRC via BMP4. RESULTS: BMP4 expression was upregulated in CRC patients, and significantly higher in CRC patients with diabetes (P < 0.05). High glucose-induced insulin resistance (IR)-CRC cells and diabetic mice with metastasis model of CRC had increased BMP4 expression, activated BMP4-Smad1/5/8 pathway, and improved proliferative and metastatic ability mediated by epithelial-mesenchymal transition (EMT). And, treated CRC cells with exogenously BMP inhibitor-Noggin or transfected with lentivirus (sh-BMP4) could block the upregulated metastatic ability of CRC cells induced by IR. Meanwhile, GLP-1R was downregulated by high glucose-induced IR while unregulated by BMP4 inhibitor noggin, and treated GLP-1RA could suppress the proliferation of CRC cells induced by IR through downregulated BMP4. CONCLUSIONS: BMP4 increased by high glucose promoted the EMT of CRC. The mechanism of the BMP4/Smad pathway was related to the susceptible metastasis of high glucose-induced IR-CRC. The commonly used hypoglycemic drug, GLP-1RA, inhibited the growth and promoted the apoptosis of CRC through the downregulation of BMP4. The result of our study suggested that BMP4 might serve as a therapeutic target in CRC patients with diabetes.

CandiHap: a haplotype analysis toolkit for natural variation study.

Haplotype blocks greatly assist association-based mapping of casual candidate genes by significantly reducing genotyping effort. The gene haplotype could be used to evaluate variants of affected traits captured from the gene region. While there is a rising interest in gene haplotypes, much of the corresponding analysis was carried out manually. CandiHap allows rapid and robust haplotype analysis and candidate identification preselection of candidate causal single-nucleotide polymorphisms and InDels from Sanger or next-generation sequencing data. Investigators can use CandiHap to specify a gene or linkage sites based on genome-wide association studies and explore favorable haplotypes of candidate genes for target traits. CandiHap can be run on computers with Windows, Mac, or UNIX platforms in a graphical user interface or command line, and applied to any species, such as plant, animal, and microbial. The CandiHap software, user manual, and example datasets are freely available at BioCode (https://ngdc.cncb.ac.cn/biocode/tools/BT007080) or GitHub (https://github.com/xukaili/CandiHap). Supplementary information: The online version contains supplementary material available at 10.1007/s11032-023-01366-4.

DROOPY LEAF1 controls leaf architecture by orchestrating early brassinosteroid signaling.

Leaf architecture directly determines canopy structure, and thus, grain yield in crops. Leaf droopiness is an agronomic trait primarily affecting the cereal leaf architecture but the genetic basis and underlying molecular mechanism of this trait remain unclear. Here, we report that DROOPY LEAF1 (DPY1), an LRR receptor-like kinase, plays a crucial role in determining leaf droopiness by controlling the brassinosteroid (BR) signaling output in Setaria, an emerging model for Panicoideae grasses. Loss-of-function mutation in DPY1 led to malformation of vascular sclerenchyma and low lignin content in leaves, and thus, an extremely droopy leaf phenotype, consistent with its preferential expression in leaf vascular tissues. DPY1 interacts with and competes for SiBAK1 and as a result, causes a sequential reduction in SiBRI1-SiBAK1 interaction, SiBRI1 phosphorylation, and downstream BR signaling. Conversely, DPY1 accumulation and affinity of the DPY1-SiBAK1 interaction are enhanced under BR treatment, thus preventing SiBRI1 from overactivation. As such, those findings reveal a negative feedback mechanism that represses leaf droopiness by preventing an overresponse of early BR signaling to excess BRs. Notably, plants overexpressing DPY1 have more upright leaves, thicker stems, and bigger panicles, suggesting potential utilization for yield improvement. The maize ortholog of DPY1 rescues the droopy leaves in dpy1, suggesting its conserved function in Panicoideae. Together, our study provides insights into how BR signaling is scrutinized by DPY1 to ensure the upward leaf architecture.

Genome-wide investigation of histone acetyltransferase gene family and its responses to biotic and abiotic stress in foxtail millet (Setaria italica [L.] P. Beauv).

BACKGROUND: Modification of histone acetylation is a ubiquitous and reversible process in eukaryotes and prokaryotes and plays crucial roles in the regulation of gene expression during plant development and stress responses. Histone acetylation is co-regulated by histone acetyltransferase (HAT) and histone deacetylase (HDAC). HAT plays an essential regulatory role in various growth and development processes by modifying the chromatin structure through interactions with other histone modifications and transcription factors in eukaryotic cells, affecting the transcription of genes. Comprehensive analyses of HAT genes have been performed in Arabidopsis thaliana and Oryza sativa. However, little information is available on the HAT genes in foxtail millet (Setaria italica [L.] P. Beauv). RESULTS: In this study, 24 HAT genes (SiHATs) were identified and divided into four groups with conserved gene structures via motif composition analysis. Phylogenetic analysis of the genes was performed to predict functional similarities between Arabidopsis thaliana, Oryza sativa, and foxtail millet; 19 and 2 orthologous gene pairs were individually identified. Moreover, all identified HAT gene pairs likely underwent purified selection based on their non-synonymous/synonymous nucleotide substitutions. Using published transcriptome data, we found that SiHAT genes were preferentially expressed in some tissues and organs. Stress responses were also examined, and data showed that SiHAT gene transcription was influenced by drought, salt, low nitrogen, and low phosphorus stress, and that the expression of four SiHATs was altered as a result of infection by Sclerospora graminicola. CONCLUSIONS: Results indicated that histone acetylation may play an important role in plant growth and development and stress adaptations. These findings suggest that SiHATs play specific roles in the response to abiotic stress and viral infection. This study lays a foundation for further analysis of the biological functions of SiHATs in foxtail millet.

A flexible organic reflectance oximeter array.

Transmission-mode pulse oximetry, the optical method for determining oxygen saturation in blood, is limited to only tissues that can be transilluminated, such as the earlobes and the fingers. The existing sensor configuration provides only single-point measurements, lacking 2D oxygenation mapping capability. Here, we demonstrate a flexible and printed sensor array composed of organic light-emitting diodes and organic photodiodes, which senses reflected light from tissue to determine the oxygen saturation. We use the reflectance oximeter array beyond the conventional sensing locations. The sensor is implemented to measure oxygen saturation on the forehead with 1.1% mean error and to create 2D oxygenation maps of adult forearms under pressure-cuff-induced ischemia. In addition, we present mathematical models to determine oxygenation in the presence and absence of a pulsatile arterial blood signal. The mechanical flexibility, 2D oxygenation mapping capability, and the ability to place the sensor in various locations make the reflectance oximeter array promising for medical sensing applications such as monitoring of real-time chronic medical conditions as well as postsurgery recovery management of tissues, organs, and wounds.

Light induces gene expression to enhance the synthesis of storage reserves in Brassica napus L. embryos.

KEY MESSAGE: In this manuscript, we disclosed the influence of light on the accumulation of storage reserves in B. napus embryos.1.Light induced the gene expression in the developing embryos of B. napus.2.Light promoted the starch synthesis in chloroplasts of B. napus embryos.3.Light enhanced the metabolic activity of storage reserve synthesis in B. napus embryos. Light influences the accumulation of storage reserves in embryos, but the molecular mechanism was not fully understood. Here, we monitored the effects of light on reserve biosynthesis in Brassica napus by comparing embryos from siliques grown in normal light conditions to those that were shaded or masked (i.e., darkened completely). Masked embryos developed more slowly, weighed less, and contained fewer proteins and lipids than control embryos. They also had fewer and smaller oil bodies than control embryos and lacked chloroplasts, where starch grains are usually synthesized. The levels of most amino acids, carbohydrates, and fatty acids were higher in masked embryos than in control or shaded embryos, whereas the levels of these metabolites in the masked endosperms were lower than those in control and shaded endosperm. Transcriptome analysis indicated that genes involved in photosynthesis (42 genes), amino acid biosynthesis (51 genes), lipid metabolism (61 genes), and sugar transport (13 genes) were significantly repressed in masked embryos. Our results suggest that light contributes to reserve accumulation in embryos by inducing the expression of metabolic genes, thereby enhancing the biosynthesis of storage reserves.

Natural variation and genomic prediction of growth, physiological traits, and nitrogen-use efficiency in perennial ryegrass under low-nitrogen stress.

Genomic prediction of nitrogen-use efficiency (NUE) has not previously been studied in perennial grass species exposed to low-N stress. Here, we conducted a genomic prediction of physiological traits and NUE in 184 global accessions of perennial ryegrass (Lolium perenne) in response to a normal (7.5 mM) and low (0.75 mM) supply of N. After 21 d of treatment under greenhouse conditions, significant variations in plant height increment (ΔHT), leaf fresh weight (LFW), leaf dry weight (LDW), chlorophyll index (Chl), chlorophyll fluorescence, leaf N and carbon (C) contents, C/N ratio, and NUE were observed in accessions , but to a greater extent under low-N stress. Six genomic prediction models were applied to the data, namely the Bayesian method Bayes C, Bayesian LASSO, Bayesian Ridge Regression, Ridge Regression-Best Linear Unbiased Prediction, Reproducing Kernel Hilbert Spaces, and randomForest. These models produced similar prediction accuracy of traits within the normal or low-N treatments, but the accuracy differed between the two treatments. ΔHT, LFW, LDW, and C were predicted slightly better under normal N with a mean Pearson r-value of 0.26, compared with r=0.22 under low N, while the prediction accuracies for Chl, N, C/N, and NUE were significantly improved under low-N stress with a mean r=0.45, compared with r=0.26 under normal N. The population panel contained three population structures, which generally had no effect on prediction accuracy. The moderate prediction accuracies obtained for N, C, and NUE under low-N stress are promising, and suggest a feasible means by which germplasm might be initially assessed for further detailed studies in breeding programs.

The signal peptide of Cry1Ia can improve the expression of eGFP or mCherry in Escherichia coli and Bacillus thuringiensis and enhance the host's fluorescent intensity.

BACKGROUND: The signal peptides (SPs) of secretory proteins are frequently used or modified to guide recombinant proteins outside the cytoplasm of prokaryotic cells. In the periplasmic space and extracellular environment, recombinant proteins are kept away from the intracellular proteases and often they can fold correctly and efficiently. Consequently, expression levels of the recombinant protein can be enhanced by the presence of a SP. However, little attention has been paid to the use of SPs with low translocation efficiency for recombinant protein production. In this paper, the function of the signal peptide of Bacillus thuringiensis (Bt) Cry1Ia toxin (Iasp), which is speculated to be a weak translocation signal, on regulation of protein expression was investigated using fluorescent proteins as reporters. RESULTS: When fused to the N-terminal of eGFP or mCherry, the Iasp can improve the expression of the fluorescent proteins and as a consequence enhance the fluorescent intensity of both Escherichia coli and Bt host cells. Real-time quantitative PCR analysis revealed the higher transcript levels of Iegfp over those of egfp gene in E. coli TG1 cells. By immunoblot analysis and confocal microscope observation, lower translocation efficiency of IeGFP was demonstrated. The novel fluorescent fusion protein IeGFP was then used to compare the relative strengths of cry1Ia (Pi) and cry1Ac (Pac) gene promoters in Bt strain, the latter promoter proving the stronger. The eGFP reporter, by contrast, cannot indicate unambiguously the regulation pattern of Pi at the same level of sensitivity. The fluorescent signals of E. coli and Bt cells expressing the Iasp fused mCherry (ImCherry) were also enhanced. Importantly, the Iasp can also enhanced the expression of two difficult-to-express proteins, matrix metalloprotease-13 (MMP13) and myostatin (growth differentiating factor-8, GDF8) in E. coli BL21-star (DE3) strain. CONCLUSIONS: We identified the positive effects of a weak signal peptide, Iasp, on the expression of fluorescent proteins and other recombinant proteins in bacteria. The produced IeGFP and ImCherry can be used as novel fluorescent protein variants in prokaryotic cells. The results suggested the potential application of Iasp as a novel fusion tag for improving the recombinant protein expression.

Correlation analysis of the transcriptome and metabolome reveals the regulatory network for lipid synthesis in developing Brassica napus embryos.

KEY MESSAGE: In this manuscript, we explored the key molecular networks for oil biosynthesis with the transcriptome and metabolome of B. napus embryo at different developmental stages. Brassica napus (B. napus) is an important oil crop worldwide, yet the molecular pathways involved in oil biosynthesis in seeds are not fully understood. In this study, we performed a combined investigation of the gene expression profiles and metabolite content in B. napus seeds at 21, 28 and 35 days after flowering (DAF), when seed oil biosynthesis takes place. The total triacylglycerol (TAG) content in seed embryos increased over the course of seed maturation, and was accompanied by changes in the fatty acid profile, an increase in lipid droplets, and a reduction in starch grains. Metabolome analysis showed that the total amino acid, free fatty acid and organic acid contents in seed embryos decreased during seed maturation. In total, the abundance of 76 metabolites was significantly different between 21 and 28 DAF, and 68 metabolites changed in abundance between 28 and 35 DAF. Transcriptome analysis showed that the set of genes differentially expressed between stages was significantly enriched in those related to lipid metabolism, transport, protein and RNA metabolism, development and signaling, covering most steps of plant lipid biosynthesis and metabolism. Importantly, the metabolite and gene expression profiles were closely correlated during seed development, especially those associated with TAG and fatty acid biosynthesis. Further, the expression of major carbohydrate metabolism-regulating genes was closely correlated with carbohydrate content during seed maturation. Our results provide novel insights into the regulation of oil biosynthesis in B. napus seeds and highlights the coordination of gene expression and metabolism in this process.

Integrated metabolite profiling and transcriptome analysis reveals a dynamic metabolic exchange between pollen tubes and the style during fertilization of Brassica napus.

KEY MESSAGE: In this study, we analyzed the transcriptome and metabolite profile of the style to explore the essential metabolites and specific genes for pollen tube growth of B. napus in vivo. For sexual reproduction of flowering plants, pollen must germinate on the stigma and the pollen tube must grow through the style to deliver the sperm nuclei to the female gametophyte cells. During this process, the rapidly growing pollen tube can cover substantial distances. Despite the clear requirements for energy and cellular building blocks in this process, few studies have examined the role of metabolism in the style for pollen tube elongation. In this study, we comprehensively analyzed the transcriptome and metabolite profiles during pollen germination and pollen tube growth in the style in Brassica napus. We profiled the transcripts and metabolites stored in pollen and identified many transcripts related to metabolic pathways. Mature pollen contained low levels of nutrients, whereas the styles contained high levels of diverse nutrients. The levels of most nutrients in the style, especially metabolites for cell wall synthesis and energy metabolism, rapidly decreased at 2 h after pollination, along with pollen germination and pollen tube elongation through the style. A subset of genes involved in cell wall synthesis and nutrient transport were expressed specifically in styles at 1 h after pollination. These results demonstrated that successful fertilization involves the transcripts and nutrients stored in mature pollen, and specific gene expression and stored nutrients in the style. Therefore, these findings enhance our understanding of fertilization in B. napus.

New association of bone morphogenetic protein 4 concentrations with fat distribution in obesity and Exenatide intervention on it.

BACKGROUND: Bone morphogenetic protein 4 (BMP-4) has been proven to regulate white adipogensis. We aimed to demonstrate the correlation of BMP-4 with fat distribution and Exenatide treatment on it. METHODS: We enrolled 69 obese patients. Anthropometric and metabolic indexes were collected. Fat distribution was measured by dual-energy X-ray absorptiometry. BPM-4 levels were assessed using enzyme-link immunosorbent assay kit. 30 obese patients were treated with Exenatide twice a day. Change in body weight, metabolic-related indices and BPM-4 levels were evaluated after 18 weeks. RESULTS: 1) The mean(±SD) BMP-4 levels were 763.98 ± 324.11 pg/ml in the obese. BPM-4 levels were significantly positively correlated with estimated visceral adipose tissue mass in all subjects and also in females (r = 0.377, r = 0.625, respectively,all P < 0.05). BPM-4 levels were also significantly positively correlated with body mass index, hip circumference and total fat% in females (r = 0.375,r = 0.429,r = 0.493,respectively, all P < 0.05). BPM-4 levels were negatively correlated with total cholesterol(TC) in all subjects and males also (r = -0.373,r = -0.332,respectively, all P < 0.05). BPM-4 levels were also significantly positively correlated with free triiodothyronine in males (r = 0.441, P < 0.05). 3) Multivariate analyses showed that TC was risk factor of BMP-4 concentration in males and Est.VAT Area was risk factor of BMP-4 levels in females. 4) BMP-4 levels were significantly higher in the obesity with slightly increased thyroid stimulating hormone(TSH) than the obesity without slightly increased TSH (902.08 ± 354.74 pg/ml vs. 720.24 ± 306.41 pg/ml, P < 0.05). 5) Exenatide treatment leads to a significant decreased in BMP-4 from 860.05 ± 352.65 pg/ml to 649.44 + 277.49 pg/ml independent of weight loss(P < 0.05). CONCLUSION: BMP-4 levels were associated with the visceral adipose tissue and may play a certain role in fat distribution and subclinical hypothyroidism in obesity. Exenatide treatment reduced BMP-4 levels independent of weight loss. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT02118376 , Registered 16 April.

Laparoscopic sleeve gastrectomy improves body composition and alleviates insulin resistance in obesity related acanthosis nigricans.

BACKGROUND: Acanthosis nigricans (AN) has a close relationship with obesity. It is believed that obesity and AN have the common pathophysiological basis such as hyperinsulinism. This study is aimed to observe the effect of laparoscopic sleeve gastrectomy (LSG) on body composition and insulin resistance in Chinese obese patients with acanthosis nigricans. METHODS: A total of 37 obese patients who underwent LSG in our hospital were selected for analysis. They were divided into simple obesity (OB n = 14) and obesity with acanthosis nigricans (AN n = 23) group respectively. Body composition was measured by dual-energy X-ray absorptiometry (DEXA). Anthropometric measurements and glucolipid metabolism before and 3 months post LSG were collected for analysis. RESULTS: Patients with AN got noticeable improvement in skin condition and their AN score was significantly decreased (3.52 ± 0.79 vs. 1.48 ± 0.73, P < 0.001).Alleviated insulin resistance and more trunk fat loss than limbs' were observed in both groups (P value < 0.01). In AN group, preoperative android fat mass (FM) was positively correlated with fasting insulin and natural logarithm of HOMA-IR (LNIR) (r = 0.622, 0.608, respectively; all P < 0.01). Besides, changes in android FM and visceral adipose tissue (VAT) also showed significantly positive correlation with changes in LNIR (r = 0.588, r = 0.598, respectively; all P < 0.01). CONCLUSIONS: LSG had a positive impact on body composition and skin condition in Chinese obese patients with AN. Loss of android FM and VAT might result in the alleviation of insulin resistance in AN patients. Android fat distribution seems to be a potential indicator of postoperative metabolic benefits for obese patients with AN.

Nutritional functions of the funiculus in Brassica napus seed maturation revealed by transcriptome and dynamic metabolite profile analyses.

The funiculus provides the sole channel of communication between the seed and the parent plant; however, little is known about its role in nutrient supply during seed maturation. Here, we investigated the dynamic metabolite profiles of the funiculus during seed maturation in Brassica napus. The funiculus was fully developed at 21 days after flowering (DAF), but the levels of nutrients, including carbohydrates, fatty acids, and amino acids, increased rapidly from 21 to 35 DAF. Orthogonal partial least squares discriminant analysis and correlation analysis identified 37 metabolites that correlated closely with seed fresh weight. To determine the influence of silique wall photosynthesis on the metabolites in the funiculus, we also covered the siliques of intact plants with aluminum foil; in these plants, the funiculus and silique wall had lower metabolite levels, compared with control. RNA-sequencing analysis of the funiculi in the dark-treated and light-exposed siliques showed that the expression of genes encoding nutrient transporters significantly increased in the funiculi in the dark-treated siliques. Furthermore, the transcripts encoding primary metabolic enzymes for amino acid synthesis, fatty acid synthesis and triacylglycerol assembly, and sucrose-starch metabolism, were also markedly up-regulated, despite the decline in metabolite levels of funiculi in the dark-treated silique. These results provide new insights into funiculus function in seed growth and synthesis of storage reserves in seeds, at the metabolic and transcriptional levels. The identification of these metabolites and genes also provides useful information for creating genetically enhanced oilseed crops with improved seed properties.

Melatonin improves non-alcoholic fatty liver disease via MAPK-JNK/P38 signaling in high-fat-diet-induced obese mice.

BACKGROUND: Melatonin can regulate lipid metabolism, increase insulin sensitivity, regulate glucose metabolism and reduce body weight. This study is aimed to determine the effects and mechanism of action of melatonin on non-alcoholic fatty liver disease (NAFLD) in high-fat-diet (HFD) induced obese mice. METHODS: NAFLD was induced by HFD in C57BL/6 mice. A total of 24 mice were randomly assigned to 4 groups. Groups A and B were fed with HFD for 36 weeks while groups C and D were fed with a regular diet (RD). During the last 12 weeks, Groups A and C were treated with 10 mg/kg melatonin while Groups B and D were treated with water in the same volume by intragastric administration. Body and liver weight, blood glucose, serum transaminases and lipid levels, and markers of hepatic inflammation were measured. Histological analyses were also performed on liver tissue. RESULTS: After 12 weeks of treatment with melatonin, body weights (Group A: before 53.11 ± 0.72 vs after 12w treatment 39.48 ± 0.74) and liver weights (A 1.93 ± 0.09 g vs B 2.92 ± 0.19 g vs C 1.48 ± 0.09 g vs D 1.49 ± 0.10 g), fasting plasma glucose, alanine transaminase (A 24.33 ± 11.90 IU/L vs B 60.80 ± 10.18 IU/L vs C 13.01 ± 3.49 IU/L vs D 16.62 ± 2.00 IU/L), and low-density cholesterol (A 0.24 ± 0.06 mmol/L vs B 1.57 ± 0.10 mmol/L vs C 0.28 ± 0.06 mmol/L vs D 0.29 ± 0.03 mmol/L) were significantly decreased in HFD mice. HFD fed mice treated with melatonin showed significantly less liver steatosis. Treatment of HFD fed mice with melatonin led to a significant decrease in the expression of TNF-α, IL-1ß, and IL-6 measured using quantitative real-time polymerase chain reaction (qRT-PCR). HFD fed mice demonstrated increased phosphorylation of P38 and JNK1/2, which was reduced by melatonin treatment. CONCLUSIONS: The study concluded that melatonin could improve NAFLD by decreasing body weight and reduce inflammation in HFD induced obese mice by modulating the MAPK-JNK/P38 signaling pathway.

Cytokinin antagonizes abscisic acid-mediated inhibition of cotyledon greening by promoting the degradation of abscisic acid insensitive5 protein in Arabidopsis.

In higher plants, seed germination is followed by postgerminative growth. One of the key developmental events during postgerminative growth is cotyledon greening, which enables a seedling to establish photosynthetic capacity. The plant phytohormone abscisic acid (ABA) plays a vital role by inhibiting seed germination and postgerminative growth in response to dynamically changing internal and environmental cues. It has been shown that abscisic acid insensitive5 (ABI5), a basic leucine zipper transcription factor, is an important factor in the regulation of the ABA-mediated inhibitory effect on seed germination and postgerminative growth. Conversely, the phytohormone cytokinin has been proposed to promote seed germination by antagonizing the ABA-mediated inhibitory effect. However, the underpinning molecular mechanism of cytokinin-repressed ABA signaling is largely unknown. Here, we show that cytokinin specifically antagonizes ABA-mediated inhibition of cotyledon greening with minimal effects on seed germination in Arabidopsis (Arabidopsis thaliana). We found that the cytokinin-antagonized ABA effect is dependent on a functional cytokinin signaling pathway, mainly involved in the cytokinin receptor gene cytokinin response1/Arabidopsis histidine kinase4, downstream histidine phosphotransfer protein genes AHP2, AHP3, and AHP5, and a type B response regulator gene, ARR12, which genetically acts upstream of ABI5 to regulate cotyledon greening. Cytokinin has no apparent effect on the transcription of ABI5. However, cytokinin efficiently promotes the proteasomal degradation of ABI5 in a cytokinin signaling-dependent manner. These results define a genetic pathway through which cytokinin specifically induces the degradation of ABI5 protein, thereby antagonizing ABA-mediated inhibition of postgerminative growth.

Coffee consumption and prostate cancer risk: a meta-analysis of cohort studies.

This meta-analysis was conducted to assess the association between coffee consumption and prostate cancer risk. Thirteen cohort studies with 34,105 cases and 539,577 participants were included in the meta-analysis. The summary relative risks (RRs) with 95% confidence intervals (CIs) for different coffee intake levels were calculated. Dose-response relationship was assessed using generalized least square trend estimation. The pooled RR for the highest vs. lowest coffee intake was 0.90 (95% CI: 0.85-0.95), with no significant heterogeneity across studies (P = 0.267; I(2) = 17.5%). The dose-response analysis showed a lower cancer risk decreased by 2.5% (RR = 0.975; 95% CI: 0.957-0.995) for every 2 cups/day increment in coffee consumption. Stratifying by geographic region, there was a statistically significant protective influence of coffee on prostate cancer risk among European populations. In subgroup analysis of prostate cancer grade, the summary RRs were 0.89 (95% CI: 0.83-0.96) for nonadvanced, 0.82 (95% CI: 0.61-1.10) for advanced and 0.76 (95% CI: 0.55-1.06) for fatal diseases. Our findings suggest that coffee consumption may be associated with a reduced risk of prostate cancer and it also has an inverse association with nonadvanced prostate cancer. Because of the limited number of studies, more prospective studies with large sample size are needed to confirm this association.

Head fat is a novel method of measuring metabolic disorder in Chinese obese patients.

BACKGROUND: Body adiposity, especially ectopic fat accumulation, has a range of metabolic and cardiovascular effects. The aim of this study was to investigate the association between head fat and metabolic values in Chinese obese patients. METHODS: Data of this cross-sectional study from 66 obese patients were collected. Fat distribution was measured by dual-energy X-ray absorptiometry, and data of body weight, body mass index (BMI), neck circumference (NC), waist circumference (WC), hip circumference (HC), visceral index, basal metabolism (BM), glucose metabolism, lipid levels, uric acid (UA) had been collected. RESULTS: 1) Head fat was significantly associated with BMI, WC, HC, visceral index, BM, total fat and total fat excluding head fat in both males and females (p<0.05). Head fat was positively correlated with upper limb fat, trunk fat, weight, fasting plasma C peptide, fasting plasma insulin and UA in women(p<0.05), and the association was not statistically significant in male (p>0.05). Head fat was positively corrected with NC in males (p<0.05) but not females (p>0.05). There was no significant correlation between head fat and fasting plasma glucose, total choleslerolemia, triglyceridemia, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and free fat acid in either gender (p>0.05). 2) Receiver operating characteristic analysis showed that a head fat of 1925.6 g and a head fat of 1567.85 g were the best cut-off values to determine subjects with low high-density lipoprotein cholesterol and hyperuricemia respectively. CONCLUSIONS: Head fat accumulation was closely associated with increased body fat, hyperinsulinemia, hyperuricemia, and impared lipid profile, suggesting it might be used as an indicator for dyslipidemia and hyperuricemia.

Genome-Wide Identification and Characterization of Alternative Oxidase (AOX) Genes in Foxtail Millet (Setaria italica): Insights into Their Abiotic Stress Response.

Alternative oxidase (AOX) serves as a critical terminal oxidase within the plant respiratory pathway, playing a significant role in cellular responses to various stresses. Foxtail millet (Setaria italica), a crop extensively cultivated across Asia, is renowned for its remarkable tolerance to abiotic stresses and minimal requirement for fertilizer. In this study, we conducted a comprehensive genome-wide identification of AOX genes in foxtail millet genome, discovering a total of five SiAOX genes. Phylogenetic analysis categorized these SiAOX members into two subgroups. Prediction of cis-elements within the promoter regions, coupled with co-expression network analysis, intimated that SiAOX proteins are likely involved in the plant's adaptive response to abiotic stresses. Employing RNA sequencing (RNA-seq) and real-time quantitative PCR (RT-qPCR), we scrutinized the expression patterns of the SiAOX genes across a variety of tissues and under multiple abiotic stress conditions. Specifically, our analysis uncovered that SiAOX1, SiAOX2, SiAOX4, and SiAOX5 display distinct tissue-specific expression profiles. Furthermore, SiAOX2, SiAOX3, SiAOX4, and SiAOX5 exhibit responsive expression patterns under abiotic stress conditions, with significant differences in expression levels observed between the shoot and root tissues of foxtail millet seedlings. Haplotype analysis of SiAOX4 and SiAOX5 revealed that these genes are in linkage disequilibrium, with Hap_2 being the superior haplotype for both, potentially conferring enhanced cold stress tolerance in the cultivar group. These findings suggest that both SiAOX4 and SiAOX5 may be targeted for selection in future breeding programs aimed at improving foxtail millet's resilience to cold stress.