Background Vascular calcification (VC), associated with enhanced cardiovascular morbidity and mortality, is characterized by the osteogenic transdifferentiation of vascular smooth muscle cells. Inflammation promotes VC initiation and progression. Interleukin (IL)-29, a newly discovered member of type III interferon, has recently been implicated in the pathogenesis of autoimmune diseases. Here we evaluated the role of IL-29 in the VC process and underlying inflammatory mechanisms. Methods and Results The mRNA expression of IL-29 was significantly increased and positively associated with an increase in BMP2 (bone morphogenetic protein 2) mRNA level in calcified carotid arteries from patients with coronary artery disease or chronic kidney disease. IL-29 and BMP2 proteins are colocalized in human calcified arteries. IL-29 binding to its specific receptor IL-28Rα (IL-28 receptor α) (IL-29/IL-28Rα) inhibited the proliferation of rat vascular smooth muscle cells without altering cell apoptosis or migration. IL-29 promoted the calcification of rat vascular smooth muscle cells and their osteogenic transdifferentiation in vitro as well as the rat aortic ring calcification ex vivo, induced by the calcification medium or osteogenic medium. The procalcification effect of IL-29 was reduced by pharmacological inhibition of IL-29/IL-28Rα binding as well as suppression of janus kinase 2/signal transducer and activator of transcription pathway activation, accompanied by decreased BMP2 expression in the cultured rat vascular smooth muscle cells. Conclusions These results suggest an important role of IL-29 in VC development, at least partly, via activating the janus kinase 2/signal transducer and activator of transcription 3 signaling. Inhibition of IL-29 or its specific receptor, IL-28Rα, may provide a novel strategy to reduce VC in patients with vascular diseases.

Photoelectrochemical (PEC) water splitting that functions in pH-neutral electrolyte attracts increasing attention to energy demand sustainability. Here, we propose a strategy to in situ form a NiB layer by tuning the composition of the neutral electrolyte with the additions of nickel and borate species, which improves the PEC performance of the BiVO4 photoanode. The NiB/BiVO4 exhibits a photocurrent density of 6.0 mA cm-2 at 1.23 VRHE with an onset potential of 0.2 VRHE under 1 sun illumination. The photoanode displays a photostability of over 600 hours in a neutral electrolyte. The additive of Ni2+ in the electrolyte, which efficiently inhibits the dissolution of NiB, can accelerate the photogenerated charge transfer and enhance the water oxidation kinetics. The borate species with B─O bonds act as a promoter of catalyst activity by accelerating proton-coupled electron transfer. The synergy effect of both species suppresses the surface charge recombination and inhibits the photocorrosion of BiVO4.

BES1, as the most important transcription factor responsible for brassinolide (BR) signaling, has been confirmed to play a significant role in regulating plant growth and the improvement of stress resistance. The transcriptional regulatory mechanism of BES1 has been well elucidated in several plants, such as Arabidopsis thaliana (A. thaliana), Triticum aestivum L. (T. aestivum), and Oryza sativa L. (O. sativa). Nevertheless, the genome-wide analysis of the BES1 family in Vitis vinifera L. (V. vinifera). has not been comprehensively carried out. Thus, we have conducted a detailed analysis and identification of the BES1 transcription factors family in V. vinifera; a total of eight VvBES1 genes was predicted, and the phylogenetic relationships, gene structures, and Cis-acting element in their promoters were also analyzed. BES1 genes have been divided into three groups (I, II and III) based on phylogenetic relationship analysis, and most of VvBES1 genes were in group III. Also, we found that VvBES1 genes was located at seven of the total nineteen chromosomes, whereas VvBES1-2 (Vitvi04g01234) and VvBES1-5 (Vitvi18g00924) had a collinearity relationship, and their three copies are well preserved. In addition, the intron-exon model of VvBES1 genes were mostly conserved, and there existed several Cis-acting elements related to stress resistance responsive and phytohormones responsive in BES1s genes promoter. Moreover, the BES1 expressions were different in different V. vinifera organs, and BES1 expressions were different in different V. vinifera varieties under saline-alkali stress and heat stress, the expression of VvBES1 also changed with the prolongation of saline-alkali stress treatment time. The above findings could not only lay a primary foundation for the further validation of VvBES1 function, but could also provide a reference for molecular breeding in V. vinifera.

Ischemic acute kidney injury (AKI) has always been a hot and difficult research topic in the field of renal diseases. This study aims to illustrate the safe warm ischemia time of kidney and the molecular network characteristics and pathological features of mild to severe ischemia reperfusion kidney injury. We established varying degrees of renal injury due to different ischemia time (0 min, 16 min, 18 min, 20 min, 22 min, 24 min, 26 min, 28 min, and 30 min) on unilateral (left kidney) ischemia-reperfusion injury and contralateral (right kidney) resection (uIRIx) mouse model. Mice were sacrificed 24 h after uIRIx, blood samples were harvested to detect serum creatinine (Scr), and kidney tissue samples were harvested to perform Periodic Acid-Schiff (PAS) staining and RNA-Seq. Differentially expressed genes (DEGs) were identificated, time-dependent gene expression patterns and functional enrichment analysis were further performed. Finally, qPCR was performed to validated RNA-Seq results. Our results indicated that there was no absolute safe renal warm ischemia time, and every minute of ischemia increases kidney damage. Warm ischemia 26min or above in mice makes severe kidney injury, renal pathology and SCr were both significantly changed. Warm ischemia between 18 and 26 min makes mild kidney injury, with changes in pathology and renal molecular expression, while SCr did not change. No obvious pathological changes but significant differences in molecular expression were found less than 16min warm ischemia. There are two key time intervals in the process of renal ischemia injury, 0 min-16 min (short-term) and 26 min-28 min (long-term). Gene expression of immune-related pathways were most significantly down-regulated in short-term ischemia, while metabolism-related pathways were the mainly enriched pathway in long-term ischemia. Taken together, this study provides novel insights into safe renal artery occlusion time in partial nephrectomy, and is of great value for elucidating molecular network characteristics and pathological features of mild to severe ischemia reperfusion kidney injury, and key genes related to metabolism and immune found in this study also provide potential diagnostic and therapeutic biomarkers for AKI.

Periodontitis is a long-term inflammatory illness and a leading contributor to tooth loss in humans. Due to the influence of the anatomic parameters of teeth, such as root bifurcation lesions and the depth of the periodontal pocket, basic periodontal treatment on its own often does not completely obliterate flora microorganisms. As a consequence, topical medication has become a significant supplement in the treatment of chronic periodontitis. Berberine (BBR) has various pharmacological effects, such as hypoglycemic, antitumor, antiarrhythmic, anti-inflammatory, etc. The target of our project is to develop a safe and non-toxic carrier that can effectively release berberine, which can significantly reduce periodontal tissue inflammation, and to investigate whether berberine thermosensitive hydrogel can exert anti-inflammatory and osteogenic effects by modulating phosphatifylinositol-3-kinase/Protein Kinase B (PI3K/AKT) signaling pathway. Consequently, firstly berberine temperature-sensitive hydrogel was prepared, and its characterizations showed that the mixed solution gelated within 3 min under 37 °C with a hole diameter of 10-130 µm, and the accumulation of berberine release amounted to 89.99% at 21 days. CCK-8 and live-dead cell staining results indicated that this hydrogel was not biotoxic, and it is also presumed that the optimum concentration of berberine is 5 µM, which was selected for subsequent experiments. Real-time polymerase chain reaction (qRT-PCR) and Western blotting (WB)results demonstrated that inflammatory factors, as well as protein levels, were significantly reduced in the berberine-loaded hydrogel group, and LY294002 (PI3K inhibitor) could enhance this effect (p < 0.05). In the berberine-loaded hydrogel group, osteogenesis-related factor levels and protein profiles were visibly increased, along with an increase in alkaline phosphatase expression, which was inhibited by LY294002 (p < 0.05). Therefore, berberine thermosensitive hydrogel may be an effective treatment for periodontitis, and it may exert anti-inflammatory and osteogenic effects through the PI3K/AKT signaling pathway.

Drought stress has significantly hampered agricultural productivity worldwide and can also result in modifications to DNA methylation levels. However, the dynamics of DNA methylation and its association with the changes in gene transcription and alternative splicing (AS) under drought stress are unknown in linseed, which is frequently cultivated in arid and semiarid regions.

Asthma is a chronic inflammatory respiratory disease, which is involved in multiple pathologic molecular mechanisms and presents a huge challenge to clinic nursing. Emerging evidence suggests that N6-methyladenosine (m6A) plays critical roles in respiratory system disease. Thus, present work tried to investigate the functions of m6A reader YTHDF 1 in asthma. The results indicated that YTHDF1 significantly upregulated in platelet-derived growth factor (PDGF) induced airway smooth muscle cells (ASMCs). Functionally, overexpression of YTHDF1 promoted the proliferation and migration of ASMCs, while YTHDF1 knockdown repressed the proliferation and migration. Mechanistically, there was a m6A modification site on cyclin D1 RNA (CCND1 genome) and YTHDF1 combined with cyclin D1 mRNA, thereby enhancing its mRNA stability via m6A-dependent manner. Collectively, these findings reveal a novel axis of YTHDF1/m6A/cyclin D1 in asthma's airway remodeling, which may provide novel therapeutic strategy for asthma.

Introduction: Wheat bran is the main by-product of wheat processing, containing about 30% pentosan and 0.4%-0.7% ferulic acid. Wheat bran is the main raw material used to prepare feruloyl oligosaccharides by hydrolysis of Xylanase, we discovered that the ability of Xylanase to hydrolyze wheat bran could be affected in the presence of different metal ions. Methods: In the present study, we have probed the effects of different metal ions on the hydrolysis activity of Xylanase on wheat bran and tried to analyze the effect of Mn2+ and Xylanase by molecular dynamic (MD) simulation. Results: Our results suggested that Mn2+ had improved the Xylanase hydrolyzing wheat bran to obtain feruloyl oligosaccharides. Particularly when the concentration of Mn2+ reached 4 mmol/L, the optimal product has been obtained 2.8 times higher to compare with no addition. Through the MD simulation analysis, our results reveal that Mn2+ can induce structural change in the active site, which enlarges the substrate binding pocket. The simulation results also revealed that the addition of Mn2+ resulted in a low RMSD value compared with the absence of Mn2+ and helped stabilize the complex. Conclusion: Mn2+ could increase the enzymatic activity of Xylanase in the hydrolysis of feruloyl oligosaccharides in wheat bran. The finding could have significant implications for the preparation of feruloyl oligosaccharides from wheat bran.

Acute oxidative stress and mitochondrial dysfunction are crucial for acute myocardial ischemia-reperfusion (AMI/R) injury, which may induce cell or mitochondrial membrane rupture and myocardial infarction. Plasma homocysteine (Hcy) expression levels are positively associated with risk of cardiovascular disease, and ERK1/2 exert anti-apoptotic and cardioprotective effects on AMI/R injury. However, the precise molecular mechanism of action underlying the effects of Hcy and the ERK1/2 signaling pathway on mitochondrial dysfunction and oxidative stress in AMI/R injury remains unclear. In the present study, AMI/R injury models were established in an animal model treated with Hcy and in H9C2 cells that were treated with hypoxia-reoxygenation. Mitochondrial function and oxidative stress were evaluated. The results demonstrated that Hcy enhanced ERK1/2 protein expression levels and oxidative stress, induced cytochrome c translocation and mitochondria dysfunction, and caused cardiac dysfunction in rats with AMI/R injury. However, an ERK1/2 inhibitor effectively protected AMI/R injury rats from Hcy-induced cardiac dysfunction and oxidative stress. In conclusion, Hcy induced mitochondrial dysfunction and oxidative stress in AMI/R injury through stimulating ROS production and the ERK1/2 signaling pathway. An ERK1/2 inhibitor may be an effective new therapeutic method for treating Hcy-induced cardiac dysfunction in patients with AMI/R injury.

Brainstem regions support vital bodily functions, yet their genetic architectures and involvement in common brain disorders remain understudied. Here, using imaging-genetics data from a discovery sample of 27,034 individuals, we identify 45 brainstem-associated genetic loci, including the first linked to midbrain, pons, and medulla oblongata volumes, and map them to 305 genes. In a replication sample of 7432 participants most of the loci show the same effect direction and are significant at a nominal threshold. We detect genetic overlap between brainstem volumes and eight psychiatric and neurological disorders. In additional clinical data from 5062 individuals with common brain disorders and 11,257 healthy controls, we observe differential volume alterations in schizophrenia, bipolar disorder, multiple sclerosis, mild cognitive impairment, dementia, and Parkinson's disease, supporting the relevance of brainstem regions and their genetic architectures in common brain disorders.

Erastin is a small molecular compound that induces ferroptosis by binding to voltage-dependent anion-selective channel protein (VDAC)2, VDAC3 and solute carrier family 7 member 5 inhibiting the cystine/glutamate antiporter. However, to the best of our knowledge, the mechanism of erastin-induced breast cancer cell death remains unclear. In present study aimed to explore the underlying mechanisms of the antitumor effects of erastin on breast cancer cells. Cellular viability was assessed using an MTT assay, a lactate dehydrogenase cytotoxicity assay kit was used to determine the cell death rate, the intracellular Fe2+ levels were determined using an iron colorimetric assay kit and western blotting was used to estimate the changes of autophagy-associated proteins levels. The present study demonstrated that erastin inhibited the viability of breast cancer cells and induced breast cancer cell death in a dose-dependent manner. Additionally, autophagy was activated by erastin, as demonstrated by upregulated expression levels of autophagy-associated proteins in breast cancer cells. Bafilomycin A1, 3-methyladenine and knockdown of autophagy related (ATG)5 with small interfering RNA prevented erastin-induced breast cancer cell death and inhibited the erastin-induced changes in the expression levels of the autophagy-associated proteins beclin1, ATG5, ATG12, microtubule-associated proteins 1A/1B light chain 3B (LC3B) and P62. Furthermore, erastin-induced breast cancer cell death was inhibited by an iron chelator, deferoxamine, which inhibited the increases of erastin-induced iron levels and inhibited the erastin-induced changes in the expression levels of the autophagy-related proteins beclin1, ATG5, ATG12, LC3B and P62. In summary, erastin triggered autophagic death in breast cancer cells by increasing intracellular iron levels.

Orthaga olivacea Warre (Lepidoptera: Pyralidae) is an important agricultural pest of camphor trees (Cinnamomum camphora). To further supplement the known genome-level features of related species, the complete mitochondrial genome of Orthaga olivacea is amplified, sequenced, annotated, analyzed, and compared with 58 other species of Lepidopteran. The complete sequence is 15,174 bp, containing 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes, 2 ribosomal RNA (rRNA) genes, and a putative control region. Base composition is biased toward adenine and thymine (79.02% A+T) and A+T skew are slightly negative. Twelve of the 13 PCGs use typical ATN start codons. The exception is cytochrome oxidase 1 (cox1) that utilizes a CGA initiation codon. Nine PCGs have standard termination codon (TAA); others have incomplete stop codons, a single T or TA nucleotide. All the tRNA genes have the typical clover-leaf secondary structure, except for trnS(AGN), in which dihydrouridine (DHU) arm fails to form a stable stem-loop structure. The A+T-rich region (293 bp) contains a typical Lepidopter motifs 'ATAGA' followed by a 17 bp poly-T stretch, and a microsatellite-like (AT)13 repeat. Codon usage analysis revealed that Asn, Ile, Leu2, Lys, Tyr and Phe were the most frequently used amino acids, while Cys was the least utilized. Phylogenetic analysis suggested that among sequenced lepidopteran mitochondrial genomes, Orthaga olivacea Warre was most closely related to Hypsopygia regina, and confirmed that Orthaga olivacea Warre belongs to the Pyralidae family.

In biology, structure is the basis of function. For plants, changes in their physiological and ecological functions are usually caused by structural changes. To understand how shading conditions change the plant structures, thereby providing structural insights into the improved yield and quality, oilseed tree peony were shaded with different densities of polyethylene nets from 28 days after pollination (DAP) until harvesting. The thickness of the leaf (LT), vein (VT), upper epidermis (UET), lower epidermis (LET), palisade tissue (PT), sponge tissue (ST), as well as the accumulation and distribution of starch, protein, and fat, were observed at 14-day intervals. The results showed that shading had a significant effect on the anatomical structure of the leaves. In the rapid growth period (before 70 DAP), the LT, ET, and VT under shading were significantly lower than under non-shading. During this period, the accumulation of starch and protein under shading was lower than that under non-shading. At the maturation period (99-112 DAP), the LT and PT under shading were higher than under non-shading, indicating that light shading delayed leaf senescence and increased photosynthetic capacity. Shading delayed the degradation of the integument cells and prolonged seed development and nutrient accumulation.

The cytochrome P450 (CYP) monooxygenase superfamily, belonging to heme-thiolate protein products, plays a vital role in metabolizing physiologically valuable compounds in plants. To date, CYP superfamily genes have not yet been characterized in grapevine (V. vinifera L.), and their functions remain unclear. In this study, a sum of 236 VvCYPs, divided into 46 families and clustered into nine clans, have been identified based on bioinformatics analyses in grapevine genome. The characteristics of both exon-intron organizations and motif structures further supported the close evolutionary relationships of VvCYP superfamily as well as the reliability of phylogenetic analysis. The gene number-based hierarchical cluster of CYP subfamilies of different plants demonstrated that the loss of CYP families seems to be limited to single species or single taxa. Promoter analysis elucidated various cis-regulatory elements related to phytohormone signaling, plant growth and development, as well as abiotic/biotic stress responses. The tandem duplication mainly contributed to the expansion of the VvCYP superfamily, followed by singleton duplication in grapevine. Global RNA-sequencing data of grapevine showed functional divergence of VvCYPs as diverse expression patterns of VvCYPs in various organs, tissues, and developmental phases, which were confirmed by quantitative real-time reverse transcription PCR (qRT-PCR). Taken together, our results provided valuable inventory for understanding the classification and biological functions of the VvCYPs and paved the way for further functional verification of these VvCYPs and are helpful to grapevine molecular breeding.

Defects introduced during the growth process greatly affect the device performance of two-dimensional (2D) materials. Here we demonstrate the applicability of employing machine-learning-based analysis to distinguish the monolayer continuous film and defect areas of molybdenum disulfide (MoS2) using position-dependent information extracted from its Raman spectra. The random forest method can analyze multiple Raman features to identify samples, making up for the problem of not being able to effectively identify by using just one certain variable with high recognition accuracy. Even some dispersed nucleation site defects can be predicted, which would commonly be ignored under an optical microscope because of the lower optical contrast. The successful application for classification and analysis highlights the potential for implementing machine learning to tap the depth of classical methods in 2D materials research.

Accumulating studies suggest that circular RNAs (circRNAs) function as key regulators in human cancers. We found that hsa_circ_0001869 participated in non-small cell lung cancer (NSCLC) progression. However, its expression and function during NSCLC remain unknown. The data advised that hsa_circ_0001869 expression was increased in NSCLC cell lines and tissues. High hsa_circ_0001869 expression had negatively correlation with the NSCLC patients prognosis. Bioinformatics and luciferase report analyses confirmed that miR-638 and FOSL2 were hsa_circ_0001869 downstream target. hsa_circ_0001869 downregulation decreased tumor proliferation, invasion and migration by promoting miR-638 expression and decreasing FOSL2 expression. As a result of overexpression of FOSL2 or silencing of miR-638, the recovery of proliferation, migration, and invasion after hsa_circ_0001869 silencing. Overexpression of FOSL2 also led to recovery of migration, invasion and proliferation after upregulation of miR-638. In vivo studies confirmed that overexpression of FOSL2 or silencing of miR-638 led to the recovery of tumor growth ability regarding A549 cells after hsa_circ_0001869 knockdown. Present investigation discovered that hsa_circ_0001869 enhanced NSCLC progression via sponging miR-638 and promoting FOSL2 expression. hsa_circ_0001869 downregulation suppressed tumor growth and invasion ability.

Coxsackievirus A6 (CV-A6) and Coxsackievirus A10 (CV-A10) have been emerging as the prevailing serotypes and overtaking Enterovirus A71 (EV-A71) and Coxsackievirus A16 (CV-A16) in most areas as main pathogens of hand, foot and mouth disease (HFMD) in China since 2013. To investigate whole etiological spectrum following EV-A71 vaccination of approximate 40,000 infants and young children in Xiangyang, enteroviruses were serotyped in 4415 HFMD cases from October 2016 to December 2017 using Real Time and conventional PCR and cell cultures. Of the typeable 3201 specimen, CV-A6 was the predominant serotype followed by CV-A16, CV-A10, CV-A5, CV-A2 and EV-A71 with proportions of 59.54%, 15.31%, 11.56%, 4.56%, 3.78% and 3.03%, respectively. Other 12 minor serotypes were also detected. The results demonstrated that six major serotypes of enteroviruses were co-circulating, including newly emerged CV-A2 and CV-A5. A dramatic decrease of EV-A71 cases was observed, whereas the total cases remained high. Multivalent vaccines against major serotypes are urgently needed for control of HFMD.

Ovarian cancer (OC) is the gynecologic cancer with the highest mortality. Circular RNAs (circRNAs) play a vital role in the development and progression of cancer. This study aimed to explore the potential role of circ_0015756 in OC and its molecular mechanism.

Bradykinin-related peptides (BRPs) family is one of the most significant myotropic peptide families derived from frog skin secretions. Here, a novel BRP callitide was isolated and identified from the red-eyed leaf frog, Agalychnis callidryas, with atypical primary structure FRPAILVRPK-NH2. The mature peptide was cleaved N-terminally at a classic propeptide convertase cleavage site (-KR-) and at the C-terminus an unusual -GKGKGK sequence was removed using the first G residue as an amide donor for the C-terminally-located K residue. Thereafter, the synthetic replicates of callitide were assessed the myotropic activity and showed a significant contraction of balder, with the 0.63 nM EC50 value, more potent than most discovered myotropic peptides. The binding mode was further speculated by molecular docking and stimulation. The result indicated that the C-terminal of callitide might selectively bind to bradykinin receptor B2 (BKRB2). Further investigation of the callitide needs to be done in the future to be exploited as potential future drug leads.

For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.