Conventional gold standard histopathologic diagnosis requires information of both high resolution structural and chemical changes in tissue. Providing optical information at ultrasonic resolution, photoacoustic (PA) technique could provide highly sensitive and highly accurate tissue characterization noninvasively in the authentic in vivo environment, offering a replacement for histopathology. A two-dimensional (2D) physio-chemical spectrogram (PCS) combining micrometer to centimeter morphology and chemical composition simultaneously can be generated for each biological sample with PA measurements at multiple optical wavelengths. This spectrogram presents a unique 2D "physio-chemical signature" for any specific type of tissue. Comprehensive analysis of PCS, termed PA physio-chemical analysis (PAPCA), can lead to very rich diagnostic information, including the contents of all relevant molecular and chemical components along with their corresponding histological microfeatures, comparable to those accessible by conventional histology. PAPCA could contribute to the diagnosis of many diseases involving diffusive patterns such as fatty liver.

Laying performance is an important economic trait in hens, and this physiological process is largely influenced by the liver function. The livers of hens at 20- and 30-week-old stages were investigated using the next generation sequencing to identify the differences of microRNA expression profiles. Compared with the 20-week-old hens, 67 down- and 13 up-regulated microRNAs were verified to be significant differentially expressed (false discovery rate, FDR ≤ 0.05) (SDE) in the 30-week-old. We also identified 13 down- and 6 up-regulated novel differentially expressed (DE) microRNAs. miR-22-3p and miR-146b-5p, which exhibit critical roles in mammalian lipid metabolism, showed the most abundant expression and the highest fold-change, respectively. A total of 648 potential target genes of the SDE microRNAs were identified through an integrated analysis of microRNAs and the DE genes obtained in previous RNA-sequencing, including FADS1, FADS2, ELOVL6 and ACSL5, which are critical lipid metabolism-related regulators. Bioinformatic analyses revealed that target genes were mainly enriched in lipid-related metabolism processes. This work provides the first study of the expression patterns of hepatic microRNAs between 20- and 30-week old hens. The findings may serve as a fundamental resource for understanding the detailed functions of microRNAs in the molecular regulatory systems of lipid metabolism.

PTPRD, encoding protein tyrosine phosphatases receptor type D, is located at chromosome 9p23-24.1, a loci frequently lost in many types of tumors. Recently, PTPRD has been proposed to function as a tumor suppressor gene. The current study aimed to investigate PTPRD expression and its prognostic significance in primary gastric adenocarcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies. Neovascularization during tumorigenesis supplies oxygen and nutrients to proliferative tumor cells, and serves as a conduit for migration. Targeting oncogenes involved in angiogenesis is needed to treat organ-confined and locally advanced ESCC. Although the phospholipase C epsilon-1 (PLCE1) gene was originally identified as a susceptibility gene for ESCC, how PLCE1 is involved in ESCC is unclear.

Deep venous thrombosis (DVT) is a common complication of orthopedic surgery. Genetic risk factors and high heritability carried a substantial risk of DVT. In this study, we aimed to investigate the potential association in the Han Chinese population between the polymorphisms of BDKRB2 and KNG1 and DVT after orthopedic surgery (DVTAOS). A total of 3,010 study subjects comprising 892 DVT cases and 2,118 controls were included in the study, and 39 single nucleotide polymorphisms (SNPs) in total (30 for BDKRB2 and 9 for KNG1) were chosen for genotyping. Two SNPs, rs710446 (OR = 1.27, P = 0.00016) and rs2069588 (OR = 1.29, P = 0.00056), were identified as significantly associated with DVTAOS. After adjusting for BMI, the significance of rs2069588 decreased (P = 0.0013). Haplotype analyses showed that an LD block containing rs2069588 significantly correlated with the DVTAOS risk. Moreover, bioinformatics analysis indicated that hsa-miR-758-5p and BDKRB2 formed miRNA/SNP target duplexes if the rs2069588 allele was in the T form, suggesting that rs2069588 may alter BDKRB2 expression by affecting hsa-miR-758-5p/single-nucleotide polymorphism target duplexes. Our results demonstrate additional evidence supporting that there is an important role for the KNG1 and BDKRB2 genes in the increased susceptibility of DVTAOS.

SKA1, an important mitosis protein, has been indicated in the initiation and progression of several malignancies. However, its clinical significance in hepatocellular carcinoma (HCC) remain to be elucidated.

Unmanned aerial vehicle (UAV) based active canopy sensors can serve as a promising sensing solution for the estimation of crop nitrogen (N) status with great applicability and flexibility. This study was endeavored to determine the feasibility of UAV-based active sensing to monitor the leaf N status of rice (Oryza sativa L.) and to examine the transferability of handheld-based predictive models to UAV-based active sensing. In this 3-year multi-locational study, varied N-rates (0-405 kg N ha-1) field experiments were conducted using five rice varieties. Plant samples and sensing data were collected at critical growth stages for growth analysis and monitoring. The portable active canopy sensor RapidSCAN CS-45 with red, red edge, and near infrared wavebands was used in handheld mode and aerial mode on a gimbal under a multi-rotor UAV. The results showed the great potential of UAV-based active sensing for monitoring rice leaf N status. The vegetation index-based regression models were built and evaluated based on Akaike information criterion and independent validation to predict rice leaf dry matter, leaf area index, and leaf N accumulation. Vegetation indices composed of near-infrared and red edge bands (NDRE or RERVI) acquired at a 1.5 m aviation height had a good performance for the practical application. Future studies are needed on the proper operation mode and means for precision N management with this system.

We compare anterior segment characteristics of Filipino- versus Chinese- and Caucasian-Americans to describe the differences in risk factors among each ethnic group.

A facile synthesis and biological applications of silver (DH-AgNps) and gold nanoparticles (DH-AuNps) mediated by the aqueous extract of Angelicae Pubescentis Radix (Du Huo) are explored. Du Huo is a medicinal root belonging to Angelica pubescens Maxim which possesses anti-inflammatory, analgesic, and antioxidant properties. The absorption spectra of nanoparticles in varying root extract and metal ion concentration, pH, reaction temperatures, and time were recorded by ultraviolet-visible (UV-Vis) spectroscopy. The presence of DH-AgNps and DH-AuNps was confirmed from the surface plasmon resonance intensified at ~414 and ~540 nm, respectively. Field emission transmission electron micrograph (FE-TEM) analysis revealed the formation of quasi-spherical DH-AgNps and spherical icosahedral DH-AuNps. These novel DH-AgNps and DH-AuNps maintained an average crystallite size of 12.48 and 7.44 nm, respectively. The biosynthesized DH-AgNps and DH-AuNps exhibited antioxidant activity against 2,2-diphenyl-1-picrylhydrzyl (DPPH) radicals and the former exhibited antimicrobial activity against clinical pathogens including Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Salmonella enterica. The expected presence of flavonoids, sesquiterpenes, and phenols on the nanoparticle surface were conjectured to grant protection against aggregation and free radical scavenging activity. DH-AgNps and DH-AuNps were further investigated for their cytotoxic properties in RAW264.7 macrophages for their potential application as drug carriers to sites of inflammation. In conclusion, this green synthesis is favorable for the advancement of plant mediated nano-carriers in drug delivery systems, cancer diagnostic, and medical imaging. Schematic diagram of biosynthesis of DH-AgNps and DH-AuNps and evaluation of their bioactivities.

Chemical composition of secondary metabolites is of great importance for quality control of agricultural products. Black sesame seeds are significantly more expensive than white sesame seeds, because it is thought that black sesame seeds are more beneficial to human health than white sesame seeds. However, the differences in nutrient composition between black sesame seeds and white sesame seeds are still unknown. The current study examined the levels of different metabolites in black and white sesame seeds via the use of a novel metabolomics strategy. Using widely targeted metabolomics data, we obtained the structure and content of 557 metabolites, out of which 217 metabolites were identified, and discovered 30 metabolic pathways activated by the secondary metabolites in both black and white sesame seeds. Our results demonstrated that the main pathways that were differentially activated included: phenylpropanoid biosynthesis, tyrosine metabolism, and riboflavin metabolism. More importantly, the biomarkers that were significantly different between black seeds and white sesame seeds are highly related to the functions recorded in traditional Chinese medicine. The results of this study may serve as a new theoretical reference for breeding experts to promote the genetic improvement of sesame seeds, and therefore the cultivation of higher quality sesame varieties.

Management for patients with diabetes experiencing myocardial infarction remains a challenge. Here the authors show that hyperglycemia- and hyperinsulinemia-induced microRNA-24 (miR-24) reduction and O-GlcNAcylation in the diabetic heart contribute to poor survival and increased infarct size in diabetic myocardial ischemia/reperfusion (I/R). In a mouse model of myocardial I/R, pharmacological or genetic overexpression of miR-24 in hearts significantly reduced myocardial infarct size. Experimental validation revealed that miR-24 targets multiple key proteins, including O-GlcNac transferase, ATG4A, and BIM, to coordinately protect the myocardium from I/R injury. These results establish miR-24 as a promising therapeutic candidate for diabetic I/R injury.

With daily electrophysiological recordings and neurochemical analysis, we uncovered a transient period of synaptic imbalance between enhanced inhibition and suppressed excitation in rat visual cortical neurons from the end of the fourth toward the end of the fifth postnatal weeks. The expression of brain-derived neurotrophic factor (BDNF), which normally enhances excitation and suppresses inhibition, was down-regulated during that time, suggesting that this may contribute to the inhibition/excitation imbalance. An agonist of the BDNF receptor tropomyosin-related kinase B (TrkB) partially reversed the imbalance, whereas a TrkB antagonist accentuated the imbalance during the transient period. Monocular lid suture during the transient period is more detrimental to the function and neurochemical properties of visual cortical neurons than before or after this period. We regard the period of synaptic imbalance as the peak critical period of vulnerability, and its existence is necessary for neurons to transition from immaturity to a more mature state of functioning.

Long non-coding RNAs (lncRNAs) that have no protein-coding capacity make up a large proportion of the transcriptome of various species. Many lncRNAs are expressed within the animal central nervous system in spatial- and temporal-specific patterns, indicating that lncRNAs play important roles in cellular processes, neural development, and even in cognitive and behavioral processes. However, relatively little is known about their in vivo functions and underlying molecular mechanisms in the nervous system. Here, we report a neural-specific Drosophila lncRNA, CASK regulatory gene (CRG), which participates in locomotor activity and climbing ability by positively regulating its neighboring gene CASK (Ca(2+)/calmodulin-dependent protein kinase). CRG deficiency led to reduced locomotor activity and a defective climbing ability-phenotypes that are often seen in CASK mutant. CRG mutant also showed reduced CASK expression level while CASK over-expression could rescue the CRG mutant phenotypes in reciprocal. At the molecular level, CRG was required for the recruitment of RNA polymerase II to the CASK promoter regions, which in turn enhanced CASK expression. Our work has revealed new functional roles of lncRNAs and has provided insights to explore the pathogenesis of neurological diseases associated with movement disorders.

Many microRNAs (miRNAs) are downregulated in proliferative vascular disease. Thus, upregulation of these miRNAs has become a major focus of research activity. However, there is a critical barrier in gene therapy to upregulate some miRNAs such as miR-145 and miR-143 because of their significant downregulation by the unclear endogenous mechanisms under disease conditions. The purpose of this study was to determine the molecular mechanisms responsible for their downregulation and to overcome the therapeutic barrier.

Autophagy is important for cells to degrade protein aggregates and organelles. Our preliminary study suggests that ischemia/reperfusion in rabbit hearts promoted autophagic myocardial injury, resulting in no-reflow phenomenon. In this study, we sought to further understand the mechanism and outcome of the upregulation of autophagy in ischemia/reperfusion.

Wheat production is of great importance for national food security and is greatly influenced by the spatial variation of climatic variables, soils, cultivars, etc. This study used WheatGrow and CERES-Wheat models integrated with a GIS to estimate winter wheat productivity, yield gap and water use in the main wheat production regions of China. The results showed that the potential wheat yield gradually increased from south to north and from west to east, with a spatial distribution consistent with the accumulated hours of sunshine. The gap between potential and actual yield varied from 382 to 7515 kg ha-1, with the highest values in Shanxi, Gansu and Shaanxi provinces and the lowest values in Sichuan province. The rainfed yield decreased gradually from south to north, roughly following the pattern of the ratio of accumulated precipitation to accumulated potential evapotranspiration. Under the scenario of autoirrigation, relatively high irrigation water use efficiency was found in western Shandong and southern Sichuan, as well as in northern Henan, Shanxi and Shaanxi. Furthermore, the limiting factors were analysed, and effective measures were suggested for improving regional winter wheat productivity. These results can be helpful for national policy making and water redistribution for agricultural production in China.

Bile acids (BAs) are important endogenous signaling molecules that play vital roles in the pathological development of various diseases including colitis-associated cancer (CAC). BAs were previously found dysregulated under conditions of CAC; however, the exact patterns and underlying molecular mechanisms remain largely elusive. Based on the development of a method for comprehensive analysis of BAs, this study aims to elucidate the dysregulation patterns and involved mechanisms in a typical CAC model induced by azoxymethane (AOM)/dextran sodium sulfate (DSS). CAC mice showed decreased BAs transformation in gut and glucuronidation in colon, leading to accumulation of primary BAs but reduction of secondary BAs in colon. CAC mice were characterized by an accumulation of BAs in various compartments except ileum, which is in line with repressed ileal FXR-FGF15 feedback signaling and the increased expression of hepatic CYP7A1. The compromised ileal FXR-FGF15 signaling was caused in part by the reduced absorption of FXR ligands including free and tauro-conjungated BAs due to the downregulation of various transporters of BAs in the ileum of CAC mice.

Alcohol addiction is a major social and health concern. Here, we determined the expression profile of microRNAs (miRNAs) in the nucleus accumbens (NAc) of rats treated with alcohol. The results suggest that multiple miRNAs were aberrantly expressed in rat NAc after alcohol injection. Among them, miR-382 was down-regulated in alcohol-treated rats. In both cultured neuronal cells in vitro and in the NAc in vivo, we identified that the dopamine receptor D1 (Drd1) is a direct target gene of miR-382. Via this target gene, miR-382 strongly modulated the expression of DeltaFosB. Moreover, overexpression of miR-382 significantly attenuated alcohol-induced up-regulation of DRD1 and DeltaFosB, decreased voluntary intake of and preference for alcohol and inhibited the DRD1-induced action potential responses. The results indicated that miRNAs are involved in and may represent novel therapeutic targets for alcoholism.

Severe forms of hypertension are characterized by high blood pressure combined with end organ damage. Through the development and refinement of a transgenic rat model of malignant hypertension incorporating the mouse renin gene, we previously identified a quantitative trait locus on chromosome 10, which affects malignant hypertension severity and morbidity. We next generated an inducible malignant hypertensive model where the timing, severity, and duration of hypertension was placed under the control of the researcher, allowing development of and recovery from end organ damage to be investigated. We have now generated novel consomic Lewis and Fischer rat strains with inducible hypertension and additional strains that are reciprocally congenic for the refined chromosome 10 quantitative trait locus. We have captured a modifier of end organ damage within the congenic region and, using a range of bioinformatic, biochemical and molecular biological techniques, have identified angiotensin-converting enzyme as the modifier of hypertension-induced tissue microvascular injury. Reciprocal differences between angiotensin-converting enzyme and the anti-inflammatory tetrapeptide, N-acetyl-Ser-Asp-Lys-Pro in the kidney, a tissue susceptible to end organ damage, suggest a mechanism for the amelioration of hypertension-dependent damage.

Reactive oxygen species (ROS)-induced cardiac cell injury via expression changes of multiple genes plays a critical role in the pathogenesis of numerous heart diseases. MicroRNAs (miRNAs) comprise a novel class of endogenous, small, noncoding RNAs that negatively regulate about 30% of the genes in a cell via degradation or translational inhibition of their target mRNAs. Currently, the effects of ROS on miRNA expression and the roles of miRNAs in ROS-mediated injury on cardiac myocytes are uncertain. Using quantitative real-time RT-PCR (qRT-PCR), we demonstrated that microRNA-21 (miR-21) was upregulated in cardiac myocytes after treatment with hydrogen peroxide (H(2)O(2)). To determine the potential roles of miRNAs in H(2)O(2)-mediated gene regulation and cellular injury, miR-21 expression was downregulated by miR-21 inhibitor and upregulated by pre-miR-21. H(2)O(2)-induced cardiac cell death and apoptosis were increased by miR-21 inhibitor and was decreased by pre-miR-21. Programmed cell death 4 (PDCD4) that was regulated by miR-21 and was a direct target of miR-21 in cardiac myocytes. Pre-miR-21-mediated protective effect on cardiac myocyte injury was inhibited in H(2)O(2)-treated cardiac cells via adenovirus-mediated overexpression of PDCD4 without miR-21 binding site. Moreover, Activator protein 1 (AP-1) was a downstream signaling molecule of PDCD4 that was involved in miR-21-mediated effect on cardiac myocytes. The results suggest that miR-21 is sensitive to H(2)O(2) stimulation. miR-21 participates in H(2)O(2)-mediated gene regulation and functional modulation in cardiac myocytes. miR-21 might play an essential role in heart diseases related to ROS such as cardiac hypertrophy, heart failure, myocardial infarction, and myocardial ischemia/reperfusion injury.