Natural variation in MORE GRAINS 1 regulates grain number and grain weight in rice.

Grain yield is determined mainly by grain number and grain weight. In this study, we identified and characterized MORE GRAINS1 (MOG1), a gene associated with grain number and grain weight in rice (Oryza sativa L.), through map-based cloning. Overexpression of MOG1 increased grain yield by 18.6%-22.3% under field conditions. We determined that MOG1, a bHLH transcription factor, interacts with OsbHLH107 and directly activates the expression of LONELY GUY (LOG), which encodes a cytokinin-activating enzyme and the cell expansion gene EXPANSIN-LIKE1 (EXPLA1), positively regulating grain number per panicle and grain weight. Natural variations in the promoter and coding regions of MOG1 between Hap-LNW and Hap-HNW alleles resulted in changes in MOG1 expression level and transcriptional activation, leading to functional differences. Haplotype analysis revealed that Hap-HNW, which results in a greater number and heavier grains, has undergone strong selection but has been poorly utilized in modern lowland rice breeding. In summary, the MOG1-OsbHLH107 complex activates LOG and EXPLA1 expression to promote cell expansion and division of young panicles through the cytokinin pathway, thereby increasing grain number and grain weight. These findings suggest that Hap-HNW could be used in strategies to breed high-yielding temperate japonica lowland rice.

A vast repertoire of secondary metabolites potentially influences community dynamics and biogeochemical processes in cold seeps.

In deep-sea cold seeps, microbial communities thrive on the geological seepage of hydrocarbons and inorganic compounds, differing from photosynthetically driven ecosystems. However, their biosynthetic capabilities remain largely unexplored. Here, we analyzed 81 metagenomes, 33 metatranscriptomes, and 7 metabolomes derived from nine different cold seep areas to investigate their secondary metabolites. Cold seep microbiomes encode diverse and abundant biosynthetic gene clusters (BGCs). Most BGCs are affiliated with understudied bacteria and archaea, including key mediators of methane and sulfur cycling. The BGCs encode diverse antimicrobial compounds that potentially shape community dynamics and various metabolites predicted to influence biogeochemical cycling. BGCs from key players are widely distributed and highly expressed, with their abundance and expression levels varying with sediment depth. Sediment metabolomics reveals unique natural products, highlighting uncharted chemical potential and confirming BGC activity in these sediments. Overall, these results demonstrate that cold seep sediments serve as a reservoir of hidden natural products and sheds light on microbial adaptation in chemosynthetically driven ecosystems.

Tributyrin Supplementation Rescues Chronic-Binge Ethanol-Induced Oxidative Stress in the Gut-Lung Axis in Mice.

Excessive alcohol consumption increases the severity and worsens outcomes of pulmonary infections, often due to oxidative stress and tissue damage. While the mechanism behind this relationship is multifaceted, recent evidence suggests ethanol-induced changes to the gut microbiome impact the gut-lung axis. To assess this, a chronic-binge ethanol feeding mouse model was used to determine how ethanol altered the gut microbiome, small intestinal epithelial barrier, and immune responses, as well as neutrophil abundance and oxidative stress in the lungs, and how supporting gut health with tributyrin supplementation during chronic-binge ethanol exposure affected these responses. We found that ethanol consumption altered gut bacterial taxa and metabolic processes, distorted small intestinal immune responses, and induced both bacteria and endotoxin translocation into the lymphatic and circulatory systems. These changes were associated with increased neutrophil (Ly6G) presence and markers of oxidative stress, lipocalin-2 and myeloperoxidase, in the lungs. Importantly, tributyrin supplementation during ethanol exposure rescued gut bacterial function (p < 0.05), small intestinal barrier integrity, and immune responses, as well as reducing both Ly6G mRNA (p < 0.05) and lipocalin-2 mRNA (p < 0.01) in the lungs. These data suggest ethanol-associated disruption of gut homeostasis influenced the health of the lungs, and that therapeutics supporting gut health may also support lung health.

The Postbiotic Butyrate Mitigates Gut Mucosal Disruption Caused by Acute Ethanol Exposure.

We aimed to test how the postbiotic butyrate impacts select gut bacteria, small intestinal epithelial integrity, and microvascular endothelial activation during acute ethanol exposure in mice and primary human intestinal microvascular endothelial cells (HIMECs). Supplementation during an acute ethanol challenge with or without tributyrin, a butyrate prodrug, was delivered to C57BL/6 mice. A separate group of mice received 3 days of clindamycin prior to the acute ethanol challenge. Upon euthanasia, blood endotoxin, cecal bacteria, jejunal barrier integrity, and small intestinal lamina propria dendritic cells were assessed. HIMECs were tested for activation following exposure to ethanol ± lipopolysaccharide (LPS) and sodium butyrate. Tributyrin supplementation protected a butyrate-generating microbe during ethanol and antibiotic exposure. Tributyrin rescued ethanol-induced disruption in jejunal epithelial barrier, elevated plasma endotoxin, and increased mucosal vascular addressin cell-adhesion molecule-1 (MAdCAM-1) expression in intestinal microvascular endothelium. These protective effects of tributyrin coincided with a tolerogenic dendritic response in the intestinal lamina propria. Lastly, sodium butyrate pre- and co-treatment attenuated the direct effects of ethanol and LPS on MAdCAM-1 induction in the HIMECs from a patient with ulcerative colitis. Tributyrin supplementation protects small intestinal epithelial and microvascular barrier integrity and modulates microvascular endothelial activation and dendritic tolerizing function during a state of gut dysbiosis and acute ethanol challenge.

Machine learning-based coronary artery calcium score predicted from clinical variables as a prognostic indicator in patients referred for invasive coronary angiography.

OBJECTIVES: Utilising readily available clinical variables, we aimed to develop and validate a novel machine learning (ML) model to predict severe coronary calcification, and further assessed its prognostic significance. METHODS: This retrospective study enrolled patients who underwent coronary CT angiography and subsequent invasive coronary angiography. Multiple ML algorithms were used to train the models for predicting severe coronary calcification (cardiac CT-measured coronary artery calcium [CT-CAC] score ≥ 400). The ML-based CAC (ML-CAC) score derived from the ML predictive probability was stratified into quartiles for prognostic analysis. The primary endpoint was a composite of all-cause death, nonfatal myocardial infarction, or nonfatal stroke. RESULTS: Overall, 5785 patients were divided into training (80%) and test sets (20%). For clinical practicability, we selected the nine-feature support vector machine model with good and satisfactory performance regarding both discrimination and calibration based on five repetitions of the 10-fold cross-validation in the training set (mean AUC = 0.715, Brier score = 0.202), and based on the test in the test set (AUC = 0.753, Brier score = 0.191). In the test set cohort (n = 1137), the primary endpoint was observed in 50 (4.4%) patients during a median 2.8 years' follow-up. The ML-CAC system was significantly associated with an increased risk of the primary endpoint (adjusted hazard ratio for trend 2.26, 95% CI 1.35-3.79, p = 0.002). There was no significant difference in the prognostic value between the ML-CAC and CT-CAC systems (C-index, 0.67 vs. 0.69; p = 0.618). CONCLUSION: ML-CAC score predicted from clinical variables can serve as a novel prognostic indicator in patients referred for invasive coronary angiography. CLINICAL RELEVANCE STATEMENT: In patients referred for invasive coronary angiography who have not undergone preoperative CT-measured coronary artery calcium scoring, machine learning-based coronary artery calcium score assessment can serve as an alternative for predicting the prognosis. KEY POINTS: • The coronary artery calcium (CAC) score, a solid prognostic indicator, can be predicted using non-CT methods. • We developed a machine learning (ML)-CAC model utilising nine clinical variables to predict severe coronary calcification. • The ML-CAC system offers significant prognostic value in patients referred for invasive coronary angiography.

A comparative study of cognitive function in young patients with bipolar disorder with and without non-suicidal self-injury.

OBJECTIVE: Bipolar disorder (BD) is a chronic mental disorder characterized by alternating or mixed episodes of mania or hypomania and depression. Cognitive function impairment is a frequent associated feature of the disease. While many BD patients also engage in non-suicidal self-injury (NSSI), there is a lack of studies on the cognitive function of BD patients with NSSI. This study aimed to evaluate cognitive functioning of BD patients with NSSI and provide a clinical basis for the differential diagnosis and treatment of BD and NSSI. METHODS: A total of 60 BD patients with NSSI, 60 BD patients without NSSI, and 60 healthy controls (HC) were selected for the study. All participants met the inclusion criteria and were not taking any medications, excluding the potential effects of medication on cognitive functions. The following neurocognitive tests were used to measure the cognitive functions in areas such as speed of processing, reasoning and problem solving, attention/vigilance, working memory, visual learning, and verbal learning: The Trail Making Test (TMT), Category Fluency, Digit Symbol Coding Test (DSCT), Brief Visuospatial Memory Test-Revised (BVMT-R), The Neuropsychological Assessment Battery Mazes (NABM), Wechsler Memory Scale Third Edition Spatial Span Test (WMS III-SST), Hopkins Verbal Learning Test-Revised (HVLTR) and Continuous Performance Test and Identical Prs (CPT-IP). RESULTS: The findings indicated that BD patients with NSSI exhibited cognitive impairment in all measured cognitive domains. On the other hand, BD patients without NSSI showed less pronounced impairment in terms of speed of processing, but exhibited significant cognitive impairment in the remaining five areas compared to the HC group. CONCLUSION: The study underscores the presence of cognitive impairment in BD, and the cognitive impairment is more severe in BD patients with NSSI compared to those without NSSI. In conclusion, both individuals with NSSI and those without NSSI in BD exhibit cognitive impairment, which provides ideas and strategies for using cognitive-behavioral therapy to treat BD and NSSI.

Palmdelphin Deficiency Evokes NF-κB Signaling in Valvular Endothelial Cells and Aggravates Aortic Valvular Remodeling.

Palmd-deficient mice of advanced age manifest increased aortic valve peak velocity, thickened aortic valve leaflets, and excessive extracellular matrix deposition, which are key features of calcific aortic valve disease. PALMD is predominantly expressed in endothelial cells of aortic valves, and PALMD-silenced valvular endothelial cells are prone to oscillatory shear stress-induced endothelial-to-mesenchymal transition. Mechanistically, PALMD is associated with TNFAIP3 interaction protein 1, a binding protein of TNFAIP3 and IKBKG in NF-κB signaling. Loss of PALMD impairs TNFAIP3-dependent deubiquitinating activity and promotes the ubiquitination of IKBKG and subsequent NF-κB activation. Adeno-associated virus-mediated PALMD overexpression ameliorates aortic valvular remodeling in mice with calcific aortic valve disease, indicating protection.

A comprehensive genomic catalog from global cold seeps.

Cold seeps harbor abundant and diverse microbes with tremendous potential for biological applications and that have a significant influence on biogeochemical cycles. Although recent metagenomic studies have expanded our understanding of the community and function of seep microorganisms, knowledge of the diversity and genetic repertoire of global seep microbes is lacking. Here, we collected a compilation of 165 metagenomic datasets from 16 cold seep sites across the globe to construct a comprehensive gene and genome catalog. The non-redundant gene catalog comprised 147 million genes, and 36% of them could not be assigned to a function with the currently available databases. A total of 3,164 species-level representative metagenome-assembled genomes (MAGs) were obtained, most of which (94%) belonged to novel species. Of them, 81 ANME species were identified that cover all subclades except ANME-2d, and 23 syntrophic SRB species spanned the Seep-SRB1a, Seep-SRB1g, and Seep-SRB2 clades. The non-redundant gene and MAG catalog is a valuable resource that will aid in deepening our understanding of the functions of cold seep microbiomes.

IL-17A induces valvular endothelial inflammation and aggravates calcific aortic valve disease.

Calcific aortic valve disease (CAVD) is an aging related disease characterized by inflammation and fibrocalcific remodeling. IL-17A is a key cytokine associated with pathophysiology of inflammatory and fibrotic disease. Previous studies showed accumulation of IL-17A-producing T helper lymphocytes in human calcified aortic valves and significantly elevated IL-17RA expression in calcified valves. However, the role of IL-17A signaling in the initiation and development of CAVD is still unclear. In this study, by analyzing public transcriptome databases, we found that IL-17A-IL-17RA signaling is activated in calcified valves. Gene expression analysis revealed significantly increased IL-17A, IL-17RA, and RUNX2 expression in calcified human aortic valves compared to in non-calcified valves, and the expression of IL-17A and IL-17RA were positively correlated with RUNX2 expression. A 5/6 nephrectomy was performed in Apoe-/- (Apoe knockout) mice to establish a CAVD mouse model. IL-17A-neutralizing antibodies significantly reduced valve calcium deposition and decreased expression of RUNX2 in aortic valves. Immunofluorescence staining of human aortic valves and qRT-PCR analysis of primary aortic valve cells revealed abundant expression of IL-17RA in valvular endothelial cells (VECs). RNA sequencing indicated that IL-17A promoted the activation of inflammatory signaling pathways in VECs. Furthermore, qRT-PCR and cytometric bead array analysis confirmed that IL-17A promoted the expression or secretion of inflammatory cytokines IL-6 and IL-1ß, chemokines CXCL2 and CXCL8, and fibrosis-related gene COL16A1. Our findings indicate that elevated IL-17A in CAVD may promote valve inflammation, fibrosis, and calcification by inducing endothelial activation and inflammation. Targeting IL-17A-IL-17RA signaling may be a potential therapeutic strategy for CAVD.

Cybervictimization and nonsuicidal self-injury: The mediating role of depressive symptoms and the moderating role of emotional reactivity.

BACKGROUND: Nonsuicidal self-injury (NSSI) has garnered growing attention in recent years, and cybervictimization (CV) has been identified as a risk factor for NSSI among adolescents. However, little is known about this association's longitudinal mediating and moderating mechanisms. Guided by the experiential avoidance model, the present study used a short longitudinal design to examine the mediating role of depressive symptoms and the moderating role of emotional reactivity between CV and NSSI. METHODS: A total of 577 Chinese middle school students (Mage = 14.38, SD = 0.67) completed the measures of CV, NSSI, depressive symptoms, and emotional reactivity. They provided data in two waves (T1 and T2, 6 months apart). RESULTS: The results found a longitudinal association between CV and NSSI as well as the mediating role of depressive symptoms. Moreover, emotional reactivity amplified the relationship between CV and NSSI via depressive symptoms; specifically, the relationship between depressive symptoms and NSSI was only significant for adolescents with high emotional reactivity. CONCLUSION: The current study has found that emotional reactivity moderated the indirect effect of depressive symptoms on the relationship between CV and NSSI. These findings have implications for the identification and intervention of NSSI in early adolescents.

Cybervictimization and non-suicidal self-injury among Chinese adolescents: A longitudinal moderated mediation model.

BACKGROUND: Cybervictimization is a risk factor for nonsuicidal self-injury (NSSI). However, there is a lack of evidence on how and under what conditions cybervictimization may influence NSSI. The present study investigated the mediating effect of self-esteem and the moderating effect of peer attachment on the relationship between cybervictimization and NSSI among Chinese adolescents. METHODS: Using three-wave longitudinal data for one year, a total of 1368 Chinese adolescents (60 % boys; Mage at Wave 1 = 15.05 years, SD = 0.85) completed the measurement using a self-report method. RESULTS: The longitudinal moderated mediation model revealed that cybervictimization is associated with NSSI via restraining the protective effect of self-esteem. Moreover, high peer attachment could buffer the negative effects of cybervictimization, and protect their self-esteem from being hurt, consequently reducing the likelihood of NSSI. LIMITATIONS: All variables in this study were self-reported, and the results should be cautiously generalized to other cultures, according to a sample of Chinese adolescents. CONCLUSIONS: Results highlight the relation between cybervictimization and NSSI. Recommended intervention and prevention strategies include enhancing the self-esteem of adolescents, breaking the cycle of cybervictimization to NSSI, and providing adolescents with more opportunities to build positive friendships with their peers to buffer the negative effects of cybervictimization.

Competition for Light Interception in Different Plant Canopy Characteristics of Diverse Cotton Cultivars.

Identifying the ideal plant nature and canopy structure is of great importance for improving photosynthetic production and the potential action of plants. To address this challenge, an investigation was accomplished in 2018 and 2019 at the Institute of Cotton Research (ICR) of the Chinese Academy of Agricultural Science (CAAS), Henan Province, China. Six cotton varieties with diverse maturities and plant canopy structures were used to evaluate the light interception (LI) in cotton, the leaf area index (LAI), the biomass, and the yield throughout the two years of study. The light spatial distribution in the plant canopy was evaluated using a geographic statistical method, following the increasing quantity of radiation intercepted, which was determined using the rules of Simpson. Compared to the cotton plants with a compact structure, varieties with both a loose and tower design captured a comparatively higher amount of light (average 31.3%) and achieved a higher LAI (average 32.4%), eventually achieving a high yield (average 10.1%). Furthermore, the polynomial correlation revealed a positive relationship between the biomass accumulation in the reproductive parts and canopy-accrued light interception (LI), signifying that light interception is critical for the yield development of cotton. Furthermore, when the leaf area index (LAI) was peaked, radiation interception and biomass reached the highest during the boll-forming stage. These findings will provide guidance on the light distribution in cotton cultivars with an ideal plant structure for light capture development, providing an important foundation for researchers to better manage light and canopies.

Critical Factors in the Implementation of Risk Awareness Education in Universities in China.

Under the influence of social changes, latent factors in campus safety are increasing, and dealing with them is becoming more difficult. Facing the challenges in the pluralistic society, students need to cope with the changes of external and internal environments in the dynamic society. Additionally, there are new events on campus at any time, which may lead to campus risk. The frequent events that have occurred on campus in recent years have created difficulties for school administrative units. Implementing campus risk management strategies and conducting risk awareness education campaigns are, therefore, necessary. The fact that we are in a technologically dynamic age is another factor that makes risk awareness and proper risk management essential for individual survival and sustainable development of organizations. The participants of the study were university students in Nanchang, Jiangxi Province. Three hundred copies of the questionnaire were distributed, and 238 valid copies were retrieved, representing a retrieval rate of 79%. The results of the survey show that "life education" is the most emphasized dimension, followed by "curriculum and instruction," and "environmental planning." The five most emphasized indicators among the 14 indicators are opportunity education, physical activity, role-play, team competition, and learning area planning. The results suggest that school administrative units can take control in an emergency and reduce the likelihood of school members being threatened or harmed by the risk factor, and educators can make a quick decision to turn risk into opportunity.

Targeting the Gut Microbiota and Host Immunity with a Bacilli-Species Probiotic during Antibiotic Exposure in Mice.

Antibiotic therapy is necessary for the treatment of bacterial infections; however, it can also disrupt the balance and function of commensal gut microbes and negatively affect the host. Probiotics have been tested as a means to counteract the negative effects of antibiotic therapy, but many probiotics are also likely destroyed by antibiotics when taken together. Here we aimed to test the efficacy of a non-pathogenic spore-forming Bacillus-species containing a probiotic blend provided during antibiotic therapy on host immune defenses in mice. Mice were exposed to antibiotics and supplemented with or without the probiotic blend and compared to control mice. Fecal and cecal contents were analyzed for gut microbes, and intestinal tissue was tested for the expression of key enzymes involved in vitamin A metabolism, serum amyloid A, and inflammatory markers in the intestine. The probiotic blend protected against antibiotic-induced overgrowth of gram-negative bacteria and gammaproteobacteria in the cecum which correlated with host immune responses. Regional responses in mRNA expression of enzymes involved with vitamin A metabolism occurred between antibiotic groups, and intestinal inflammatory markers were mitigated with the probiotic blend. These data suggest prophylactic supplementation with a spore-forming Bacillus-containing probiotic may protect against antibiotic-induced dysregulation of host immune responses.

Active metabolism and biomass dynamics of biocrusts are shaped by variation in their successional state and seasonal energy sources.

Seasonal growth and changes in biomass within communities are the core of ecosystem dynamics. Biocrusts play a prominent role as pioneers in dryland soils. However, the seasonal dynamics of biocrusts remain poorly resolved. In this study, we collected biocrusts across a successional gradient (cyanobacteria, cyanolichen, chlorolichen, and moss-dominated) from southeastern Tengger Desert (China) during the summer and autumn seasons, and explored seasonal changes in metabolism and biomass using multi-omics approaches. We found that Cyanobacteria and Ascomycota were the dominant active taxa and both exhibited higher abundances in autumn. We also found that the dominant primary producers in biocrusts strongly affected community-wide characteristics of metabolism. Along with seasonal differences in light energy utilization, utilization of inorganic energy sources exhibited higher expression in the summer while for organic sources, in the autumn. We found that overall metabolism was significantly regulated by the ratio of intracellular to extracellular polymer degradation, and affected by NO3-, PO43- and EC (in the summer)/NO2- (in the autumn). In summary, biocrust growth varied with seasonal variation in light energy utilization and complementary chemical energy sources, with the most suitable season varying with biocrust successional type.

Carbon footprint of cotton production in China: Composition, spatiotemporal changes and driving factors.

Analyzing the carbon footprint of crop production and proposing low-carbon emission reduction production strategies can help China develop sustainable agriculture under the goal of 'carbon peak and carbon neutrality'. Cotton is an economically important crop in China, but few reports have systematically quantified the carbon footprint of China's cotton production and analyzed its spatiotemporal changes and driving factors. This study used a life cycle approach to analyze the spatiotemporal changes and identify the main components and driving factors of the carbon footprint of cotton production in China between 2004 and 2018 based on statistical data. The results showed that the carbon footprint per unit area of cotton in Northwest China, the Yellow River Basin and the Yangtze River Basin reached 6220.13 kg CO2eq·ha-1, 3528.14 kg CO2eq·ha-1 and 2958.56 kg CO2eq·ha-1, respectively. From 2004 to 2018, the CFa in the Yellow River Basin and Northwest China increased annually, with average increases of 59.87 kg CO2eq·ha-1 and 260.70 kg CO2eq·ha-1, respectively, while the CFa in the Yangtze River Basin decreased by an average of 21.53 kg CO2eq·ha-1 per year. The ridge regression and Logarithmic Mean Divisia Index (LMDI) model showed that fertilizer, irrigation electricity and agricultural film were the main influences on carbon emission growth at the micro level and that the economic factor was the key factor at the macro level. Improving the efficiency of cotton fertilization and electricity use and ensuring the high-quality development of the cotton industry are effective strategies to reduce the carbon footprint of cotton cultivation in the future. This study comprehensively uses statistical data and mathematical modeling to provide theoretical support for accounting and in-depth analysis of cotton carbon emissions. The results are valuable for policy making related to sustainable development and the low-carbon development of the Chinese cotton industry.

miRNA Expression Profiling Uncovers a Role of miR-139-5p in Regulating the Calcification of Human Aortic Valve Interstitial Cells.

Calcific aortic valve disease (CAVD) is the most common structural heart disease, and the morbidity is increased with elderly population. Several microRNAs (miRNAs) have been identified to play crucial roles in CAVD, and numerous miRNAs are still waiting to be explored. In this study, the miRNA expression signature in CAVD was analyzed unbiasedly by miRNA-sequencing, and we found that, compared with the normal control valves, 152 miRNAs were upregulated and 186 miRNAs were downregulated in calcified aortic valves. The functions of these differentially expressed miRNAs were associated with cell differentiation, apoptosis, adhesion and immune response processes. Among downregulated miRNAs, the expression level of miR-139-5p was negatively correlated with the osteogenic gene RUNX2, and miR-139-5p was also downregulated during the osteogenic differentiation of primary human aortic valve interstitial cells (VICs). Subsequent functional studies revealed that miR-139-5p overexpression inhibited the osteogenic differentiation of VICs by negatively modulating the expression of pro-osteogenic gene FZD4 and CTNNB1. In conclusion, these results suggest that miR-139-5p plays an important role in osteogenic differentiation of VICs via the Wnt/ß-Catenin pathway, which may further provide a new therapeutic target for CAVD.

[Arachidonic acid Alox15/12-HETE signaling inhibits vascular calcification].

This study aims to explore the effects of arachidonic acid lipoxygenase metabolism in vascular calcification. We used 5/6 nephrectomy and high-phosphorus feeding to establish a model of vascular calcification in mice. Six weeks after nephrectomy surgery, vascular calcium content was measured, and Alizarin Red S and Von Kossa staining were applied to detect calcium deposition in aortic arch. Control aortas and calcified aortas were collected for mass spectrometry detection of arachidonic acid metabolites, and active molecules in lipoxygenase pathway were analyzed. Real-time quantitative PCR was used to detect changes in the expression of lipoxygenase in calcified aortas. Lipoxygenase inhibitor was used to clarify the effect of lipoxygenase metabolic pathways on vascular calcification. The results showed that 6 weeks after nephrectomy surgery, the aortic calcium content of the surgery group was significantly higher than that of the sham group (P < 0.05). Alizarin Red S staining and Von Kossa staining showed obvious calcium deposition in aortic arch from surgery group, indicating formation of vascular calcification. Nine arachidonic acid lipoxygenase metabolites were quantitated using liquid chromatography/mass spectrometry (LC-MS) analysis. The content of multiple metabolites (12-HETE, 11-HETE, 15-HETE, etc.) was significantly increased in calcified aortas, and the most abundant and up-regulated metabolite was 12-HETE. Furthermore, we examined the mRNA levels of metabolic enzymes that produce 12-HETE in calcified blood vessels and found the expression of arachidonate lipoxygenase-15 (Alox15) was increased. Blocking Alox15/12-HETE by Alox15 specific inhibitor PD146176 significantly decreased the plasma 12-HETE content, promoted calcium deposition in aortic arch and increased vascular calcium content. These results suggest that the metabolism of arachidonic acid lipoxygenase is activated in calcified aorta, and the Alox15/12-HETE signaling pathway may play a protective role in vascular calcification.

[Effect of arachidonic acid cytochrome P450ω hydroxylase Cyp4a14 gene knockout on skeletal muscle regeneration after injury].

The objective of this study was to explore the roles of arachidonic acid cytochrome P450ω hydroxylase CYP4A14 in skeletal muscle regeneration after injury. Wild-type (WT) control mice and Cyp4a14 knockout (A14-/-) mice were used to establish the muscle injury and regeneration model by intramuscular injection with cardiotoxin (CTX) on the tibial anterior (TA) muscle. The TA muscles were harvested at the time points of 0, 3, 5 and 15 days after injury. The changes in skeletal muscle regeneration and fibrosis were assessed by wheat germ agglutinin (WGA) staining and Sirius Red staining. Immunohistochemical staining was used to observe the expression of proliferation-related protein Ki-67 and macrophage marker protein Mac-2. The mRNA levels of regeneration and inflammation associated genes were analyzed by real-time PCR. The results showed that the cross-section area (CSA) of regenerated myofibers in A14-/- mice was significantly smaller (P < 0.05), while the percentage of fibrosis area was significantly higher than those in WT mice at 15 days after injury (P < 0.05). In A14-/- muscles, both the ratio of Ki-67 positive proliferating cells and the mRNA levels of differentiation associated genes Myod1 and Myog were significantly lower than those in WT muscles (P < 0.05). At 3 days after injury, the mRNA expression of inflammatory cells marker genes CD45 and CD11b and Mac-2 positive macrophages in A14-/- muscles were significantly lower than those in WT skeletal muscle (P < 0.05). Macrophages derived pro-regeneration cytokines IL-1ß, IGF-1 and SDF-1 were also significantly decreased in A14-/- muscles (P < 0.05). These results suggest that arachidonic acid cytochrome P450ω hydroxylase CYP4A14 plays a critical role in skeletal muscle regeneration after injury.

Metagenomic Insight Into Patterns and Mechanism of Nitrogen Cycle During Biocrust Succession.

The successional ecology of nitrogen cycling in biocrusts and the linkages to ecosystem processes remains unclear. To explore this, four successional stages of natural biocrust with five batches of repeated sampling and three developmental stages of simulated biocrust were studied using relative and absolute quantified multi-omics methods. A consistent pattern across all biocrust was found where ammonium assimilation, mineralization, dissimilatory nitrite to ammonium (DNiRA), and assimilatory nitrate to ammonium were abundant, while denitrification medium, N-fixation, and ammonia oxidation were low. Mathematic analysis showed that the nitrogen cycle in natural biocrust was driven by dissolved organic N and NO3 -. pH and SO4 2- were the strongest variables affecting denitrification, while C:(N:P) was the strongest variable affecting N-fixation, DNiRA, nitrite oxidation, and dissimilatory nitrate to nitrite. Furthermore, N-fixation and DNiRA were closely related to elemental stoichiometry and redox balance, while assimilatory nitrite to ammonium (ANiRA) and mineralization were related to hydrological cycles. Together with the absolute quantification and network models, our results suggest that responsive ANiRA and mineralization decreased during biocrust succession; whereas central respiratory DNiRA, the final step of denitrification, and the complexity and interaction of the whole nitrogen cycle network increased. Therefore, our study stresses the changing environmental functions in the biocrust N-cycle, which are succession-dependent.