An unusual cause of hemorrhagic shock in a 14-year-old child.

A 14-year-old girl underwent colonoscopy due to repeated flesh-washing watery stools and dull pain around the umbilicus for 10 days. She felt tired for 1 month with no other significant discomfort. The hemoglobin (Hb) is 66g/L, and the red blood cell (RBC) count was 3.24*10^12/L in routine blood tests at admission. Abdominal computed tomography (CT) images showed submucosal tumor (SMT) in the descending colon. The abdominal computed tomography (CT) images showed submucosal tumor (SMT) in the descending colon. The SMT, supplied by the superior and inferior mesenteric arteries, showed significant enhancement at the arterial stage. It did not reveal any bowel wall thickening, enlarged lymph nodes, or ascites, suggesting that the SMT was probably a benign submucosal lesion. The submucosal tumor lesion measured in size 25*25mm located at the descending colon. Endoscopic ultrasonography imaging showed a mixed hyperechoic with a regular edge, originating from the submucosa and closely related to the muscularis propria. There were no evident features of malignancy or metastasis. Endoscopic full-thickness resection (EFR) was carried out for en bloc resection. The tumor was located in the submucosa with a clear boundary and intact capsule. The tumor cells exhibited acinar and nested patterns with abundant thin-walled blood vessels. These tumor cells were epithelioid, displaying abundant clear or eosinophilic cytoplasm. The nuclei were round or oval. Immunohistochemical analysis revealed that the tumor cells showed positive staining for HMB-45 and TFE3, but were negative for SMA.

Effects of selective cyclooxygenase-2 inhibitor robenacoxib on primary cells derived from feline injection-site sarcoma.

Feline injection-site sarcomas (FISSs) are highly invasive malignant mesenchymal neoplasms that arise from injection sites in cats. Although the tumorigenesis of FISSs is still uncertain, there is a consensus that FISS is associated with chronic inflammation caused by irritation of injection-related trauma and foreign chemical substances. Chronic inflammation can provide a proper microenvironment for tumour development, which has been known as one of the risk factors of tumorigenesis in many tumours. To investigate the tumorigenesis of FISS and screen for its potential therapeutic targets, cyclooxygenase-2 (COX-2), an inflammation-enhancing enzyme, was selected as a target for this study. In vitro experiments using FISS- and normal tissue-derived primary cells and robenacoxib, a highly selective COX-2 inhibitor, were performed. The results demonstrated that expression of COX-2 could be detected in formalin-fixed and paraffin-embedded FISS tissues and FISS-derived primary cells. Cell viability, migration and colony formation of FISS-derived primary cells were inhibited, and cell apoptosis was enhanced by robenacoxib in a dose-dependent manner. However, susceptibility to robenacoxib varied in different lines of FISS primary cells and was not completely correlated with COX-2 expression. Our results suggest that COX-2 inhibitors could be potential adjuvant therapeutics against FISSs.

A calmodulin-like protein (CML10) interacts with cytosolic enzymes GSTU8 and FBA6 to regulate cold tolerance.

Calmodulin-like proteins (CMLs) are calcium (Ca2+) sensors involved in plant growth and development as well as adaptation to environmental stresses; however, their roles in plant responses to cold are not well understood. To reveal the role of MsCML10 from alfalfa (Medicago sativa) in regulating cold tolerance, we examined transgenic alfalfa and Medicago truncatula overexpressing MsCML10, MsCML10-RNAi alfalfa, and a M. truncatula cml10-1 mutant and identified MsCML10-interacting proteins. MsCML10 and MtCML10 transcripts were induced by cold treatment. Upregulation or downregulation of MsCML10 resulted in increased or decreased cold tolerance, respectively, while cml10-1 showed decreased cold tolerance that was complemented by expressing MsCML10, suggesting that MsCML10 regulates cold tolerance. MsCML10 interacted with glutathione S-transferase (MsGSTU8) and fructose 1,6-biphosphate aldolase (MsFBA6), and the interaction depended on the presence of Ca2+. The altered activities of Glutathione S-transferase and FBA and levels of ROS and sugars were associated with MsCML10 transcript levels. We propose that MsCML10 decodes the cold-induced Ca2+ signal and regulates cold tolerance through activating MsGSTU8 and MsFBA6, leading to improved maintenance of ROS homeostasis and increased accumulation of sugars for osmoregulation, respectively.

Genome-Wide Analysis of the MADS-Box Gene Family in Hibiscus syriacus and Their Role in Floral Organ Development.

Hibiscus syriacus belongs to the Malvaceae family, and is a plant with medicinal, edible, and greening values. MADS-box transcription factor is a large family of regulatory factors involved in a variety of biological processes in plants. Here, we performed a genome-wide characterization of MADS-box proteins in H. syriacus and investigated gene structure, phylogenetics, cis-acting elements, three-dimensional structure, gene expression, and protein interaction to identify candidate MADS-box genes that mediate petal developmental regulation in H. syriacus. A total of 163 candidate MADS-box genes were found and classified into type I (Mα, Mß, and Mγ) and type II (MIKC and Mδ). Analysis of cis-acting elements in the promoter region showed that most elements were correlated to plant hormones. The analysis of nine HsMADS expressions of two different H. syriacus cultivars showed that they were differentially expressed between two type flowers. The analysis of protein interaction networks also indicated that MADS proteins played a crucial role in floral organ identification, inflorescence and fruit development, and flowering time. This research is the first to analyze the MADS-box family of H. syriacus and provides an important reference for further study of the biological functions of the MADS-box, especially in flower organ development.

Pyrolysis Atmospheres and Temperatures Co-Mediated Spectral Variations of Biochar-Derived Dissolved Organic Carbon: Quantitative Prediction and Self-Organizing Maps Analysis.

Biochar-derived dissolved organic carbon (BDOC), as a highly activated carbonaceous fraction of biochar, significantly affects the environmental effect of biochar. This study systematically investigated the differences in the properties of BDOC produced at 300-750 °C in three atmosphere types (including N2 and CO2 flows and air limitation) as well as their quantitative relationship with biochar properties. The results showed that BDOC in biochar pyrolyzed in air limitation (0.19-2.88 mg/g) was more than that pyrolyzed in N2 (0.06-1.63 mg/g) and CO2 flows (0.07-1.74 mg/g) at 450-750 °C. The aliphaticity, humification, molecular weight, and polarity of BDOC strongly depended on the atmosphere types as well as the pyrolysis temperatures. BDOC produced in air limitation contained more humic-like substances (0.65-0.89) and less fulvic-like substances (0.11-0.35) than that produced in N2 and CO2 flows. The multiple linear regression of the exponential form of biochar properties (H and O contents, H/C and (O+N)/C) could be used to quantitatively predict the bulk content and organic component contents of BDOC. Additionally, self-organizing maps could effectively visualize the categories of fluorescence intensity and components of BDOC from different pyrolysis atmospheres and temperatures. This study highlights that pyrolysis atmosphere types are a crucial factor controlling the BDOC properties, and some characteristics of BDOC can be quantitatively evaluated based on the properties of biochar.

More than causing (epi)genomic instability: emerging physiological implications of transposable element modulation.

Transposable elements (TEs) initially attracted attention because they comprise a major portion of the genomic sequences in plants and animals. TEs may jump around the genome and disrupt both coding genes as well as regulatory sequences to cause disease. Host cells have therefore evolved various epigenetic and functional RNA-mediated mechanisms to mitigate the disruption of genomic integrity by TEs. TE associated sequences therefore acquire the tendencies of attracting various epigenetic modifiers to induce epigenetic alterations that may spread to the neighboring genes. In addition to posting threats for (epi)genome integrity, emerging evidence suggested the physiological importance of endogenous TEs either as cis-acting control elements for controlling gene regulation or as TE-containing functional transcripts that modulate the transcriptome of the host cells. Recent advances in long-reads sequence analysis technologies, bioinformatics and genetic editing tools have enabled the profiling, precise annotation and functional characterization of TEs despite their challenging repetitive nature. The importance of specific TEs in preimplantation embryonic development, germ cell differentiation and meiosis, cell fate determination and in driving species specific differences in mammals will be discussed.

Genome-Wide Identification and Characterization of Short-Chain Dehydrogenase/Reductase (SDR) Gene Family in Medicago truncatula.

Short-chain dehydrogenase/reductase (SDR) belongs to the NAD(P)(H)-dependent oxidoreductase superfamily. Limited investigations reveal that SDRs participate in diverse metabolisms. A genome-wide identification of the SDR gene family in M. truncatula was conducted. A total of 213 MtSDR genes were identified, and they were distributed on all chromosomes unevenly. MtSDR proteins were categorized into seven subgroups based on phylogenetic analysis and three types including 'classic', 'extended', and 'atypical', depending on the cofactor-binding site and active site. Analysis of the data from M. truncatula Gene Expression Atlas (MtGEA) showed that above half of MtSDRs were expressed in at least one organ, and lots of MtSDRs had a preference in a tissue-specific expression. The cis-acting element responsive to plant hormones (salicylic acid, ABA, auxin, MeJA, and gibberellin) and stresses were found in the promoter of some MtSDRs. Many genes of MtSDR7C,MtSDR65C, MtSDR110C, MtSDR114C, and MtSDR108E families were responsive to drought, salt, and cold. The study provides useful information for further investigation on biological functions of MtSDRs, especially in abiotic stress adaptation, in the future.

The paradox of aging and health-related quality of life in Asian Chinese: results from the Healthy Aging Longitudinal Study in Taiwan.

BACKGROUND: Declines in health, physical, cognitive, and mental function with age suggest a lower level of health-related quality of life (HRQoL) in late life; however, previous studies found that the associations were weak and varied, depending on the study designs and cohort characteristics. METHODS: The present study examined the paradox of aging in an East Asian context by regressing the age patterns of objective health indicators (physical, cognitive, and mental function), and subjective HRQoL (12-item Short Form, SF-12), on the independent and interactive effects of age and physical function in a cohort study of 5022 community-dwelling adults aged 55 and older in Taiwan. RESULTS: Age patterns differed across measures. The SF-12 mental health score (MCS) showed a slight positive association with age and this effect remained stable after controlling for various age-related covariates. The SF-12 physical health score (PCS), in turn, was negatively associated with age. Age differences in PCS were fully explained by age decrements in objective physical health. However, consistent with the so-called paradox of aging, the association between objective and subjective physical health weakened with age. CONCLUSION: These findings add to prior evidence indicating that - in spite of objective health decrements - subjective HRQoL is maintained in later life among Asian Chinese. Also, these paradoxical patterns appear to vary for mental and physical components of HRQoL, and future research is needed to explore the underlying mechanism. TRIAL REGISTRATION: Healthy Aging Longitudinal Study in Taiwan (HALST) is retrospectively registered at ClinicalTrials.gov on January 24, 2016 with trial registration number NCT02677831.

Calmodulin-Like (CML) Gene Family in Medicago truncatula: Genome-Wide Identification, Characterization and Expression Analysis.

Calcium is an important second messenger in mediating adaptation responses of plants to abiotic and biotic stresses. Calmodulin-like (CML) protein is an important calcium-signaling protein that can sense and decode Ca2+ signal in plants. Medicago truncatula is a model legume plant; however, investigations of MtCML proteins are limited. Using genome analysis and BLAST database searches, fifty MtCML proteins that possess EF-hand motifs were identified. Phylogenetic analysis showed that CML homologs between M. truncatula, Arabidopsis thaliana and Oryza sativa shared close relationships. Gene structure analysis revealed that these MtCML genes contained one to four conserved EF-hand motifs. All MtCMLs are localized to eight chromosomes and underwent gene duplication. In addition, MtCML genes were differentially expressed in different tissues of M. truncatula. Cis-acting elements in promoter region and expression analysis revealed the potential response of MtCML protein to abiotic stress and hormones. The results provide a basis of further functional research on the MtCML gene family and facilitate their potential use for applications in the genetic improvement on M. truncatula in drought, cold and salt stress environments.

A role for paracrine interleukin-6 signaling in the tumor microenvironment in prostate tumor growth.

BACKGROUND: Interleukin-6 (IL-6) is a mediator of inflammation that can facilitate prostate cancer progression. We previously demonstrated that IL-6 is present in the prostate tumor microenvironment and is restricted almost exclusively to the stromal compartment. The present study examined the influence of paracrine IL-6 signaling on prostate tumor growth using allograft models of mouse prostate cancer (TRAMP-C2), colon cancer (MC38), and melanoma (B16) cell lines in wildtype (WT) and IL-6 knockout (IL-6-/- ) mice. METHODS: Cells were implanted into WT or IL-6-/- mice and tumor sizes were measured at a 3 to 4 day interval. Serum, tumors, and other organs were collected for IL-6 analysis by ELISA and RNA in situ hybridization (RISH). RESULTS: There was a significant reduction in TRAMP-C2 and B16 tumor size grown in IL-6-/- mice versus WT mice (P = 0.0006 and P = 0.02, respectively). This trend was not observed for the MC38 cell line. RISH analysis of TRAMP-C2 tumors grown in WT mice showed that cells present in the tumor microenvironment were the primary source of IL-6 mRNA, not the TRAMP-C2 cells. Serum IL-6 ELISA analyses showed an increase in the circulating levels of IL-6 in WT mice bearing TRAMP-C2 tumors. Similar phospho-STAT3 expression and tumor vascularization were observed in TRAMP-C2 tumors grown in WT and IL-6-/- mice. CONCLUSIONS: Our results are consistent with previous studies in prostate cancer patients demonstrating that paracrine IL-6 production in the tumor microenvironment may influence tumor growth. Additionally, these data provide evidence that elevated systemic IL-6 levels may be involved in tumor growth regulation in prostate cancer, and are not simply caused by or indicative of tumor burden.

Profiling the Urinary Microbiome in Men with Positive versus Negative Biopsies for Prostate Cancer.

PURPOSE: Studies demonstrating bacterial DNA and cultivable bacteria in urine samples have challenged the clinical dogma that urine is sterile. Furthermore, studies now indicate that dysbiosis of the urinary microbiome is associated with pathological conditions. We propose that the urinary microbiome may influence chronic inflammation observed in the prostate, leading to prostate cancer development and progression. Therefore, we profiled the urinary microbiome in men with positive vs negative biopsies for prostate cancer. MATERIALS AND METHODS: Urine was collected from men prior to biopsy for prostate cancer. DNA was extracted from urine pellet samples and subjected to bacterial 16S rDNA Illumina® sequencing and 16S rDNA quantitative polymerase chain reaction. We determined the association between bacterial species and the presence or absence of cancer, cancer grade, and type and degree of prostate inflammation. RESULTS: Urine samples revealed diverse bacterial populations. There were no significant differences in α or ß diversity and no clear hierarchical clustering of benign or cancer samples. We identified a cluster of pro-inflammatory bacteria previously implicated in urogenital infections in a subset of samples. Many species, including known uropathogens, were significantly and differentially abundant among cancer and benign samples, in low vs higher grade cancers and in relation to prostate inflammation type and degree. CONCLUSIONS: To our knowledge we report the most comprehensive study to date of the male urinary microbiome and its relationship to prostate cancer. Our results suggest a prevalence of pro-inflammatory bacteria and uropathogens in the urinary tract of men with prostate cancer.

Sedative-hypnotic drug use among community-dwelling elderly in Taiwan.

ABSTRACTBackground:Sedative-hypnotic medication use has been related to severe adverse events and risks. This study investigated the prevalence of and characteristics associated with the use of sedatives and hypnotics among community-dwelling elderly persons aged 65 years and over in Taiwan. METHODS: A representative sample of community-dwelling adults was recruited. Clinical and sociodemographic data were collected for assessing physical, mental, and cognitive functioning and disorders. Sedatives and hypnotics use was determined via both self-reporting and prescription records. Logistic regression modeling was used to evaluate associations between sedative-hypnotic use and demographic and health status. RESULTS: Among the 3,978 participants aged 65 years and over, the rate of sedative-hypnotic use was 19.7% (n = 785). 4.5% (n = 35) of users reported sedative-hypnotic use without a doctor's prescription. Several sociodemographic characteristics were positively associated with sedative and hypnotic use, including older age, female gender, higher education level, married status, unemployment, and current alcohol consumption. Comorbid chronic and cardiovascular diseases, mental illness, depression, pain, and sleep problems also increased the likelihood of sedative-hypnotic use. CONCLUSIONS: This study is one of the largest pioneer studies to date to survey sedatives-hypnotics use among community-dwelling elderly. One in five community-dwelling older adults reported sedative-hypnotic drugs use in Taiwan, and about 5% of sedative and/or hypnotics usage was without a doctor's prescription. Findings could be helpful for drug-use safety interventions to identify target geriatric patients who are in general at higher risk of downstream harm associated with sedative-hypnotic use in geriatric patients.

Moderating effect of depression on the association between pain and activities of daily living in older adults.

BACKGROUND: Maintaining older adults' ability to function independently in the community is a critically important public health concern. One of the most common symptoms threatening that ability is pain. Depression is a common co-occurring symptom in older adults with pain. In the present study, we determined the moderating effect of depression on the association between pain and functional limitations. METHODS: Data were from the Healthy Aging Longitudinal Study in Taiwan, a population-based study of community-dwelling older adults in Taiwan (N = 2680). All data were collected by face-to-face interviews. Sociodemographic and health-related factors along with the location and severity of pain were collected. Functional limitation was assessed using the Barthel Index of Activities of Daily Living, whereas depression was assessed using the Center for Epidemiologic Studies Depression Scale. RESULTS: Pain presence was not significantly associated with functional limitation, but overall pain severity and number of pain sites were. Depressive older adults exhibited a stronger association of pain and functional limitation. CONCLUSION: Depression moderates the relation between pain and functional limitation. This knowledge may be valuable in developing effective public health and clinical management strategies to reduce functional limitation in older adults.

Prevalence of and risk factors for minor and major depression among community-dwelling older adults in Taiwan.

BACKGROUND: This study was conducted to estimate prevalence rates and risk factors for late-life depression in a large nationwide representative sample from Taiwan. METHODS: A total of 5,664, randomly sampled individuals aged ≥55 years were enrolled. Clinically, relevant depressive symptoms were classified using the Center for Epidemiological Studies Depression Scale (CES-D score ≥16), and major depression was confirmed using the Primary Care Evaluation of Mental Disorders. Individuals with clinically relevant depressive symptoms, who did not meet the strict diagnostic criteria for major depression, were considered to have minor depression. Multinomial logistic regression analyses were conducted to identify risk factors for major and minor depression, including socio-demographic characteristics, medical conditions, lifestyle behaviors, social support network, and life events. RESULTS: The prevalence rates of minor and major depression were 3.7% and 1.5%, respectively. Major depression was associated with personal vulnerability factors, such as poor social support, cognitive impairment, comorbid pain conditions, and sleep disturbance. However, minor depression was more likely to be related to adverse life events, including increased burden on families, changes in health status, or relationship problem. Approximately, 20.0% of individuals with major depression received antidepressant treatment. CONCLUSIONS: Late-life depression was less prevalent among community-dwelling older adults in Taiwan than among populations in other countries. Our findings may aid the early detection and treatment of late-life depression and provide a basis for future investigations.

Tumorigenicity of hypoxic respiring cancer cells revealed by a hypoxia-cell cycle dual reporter.

Although aerobic glycolysis provides an advantage in the hypoxic tumor microenvironment, some cancer cells can also respire via oxidative phosphorylation. These respiring ("non-Warburg") cells were previously thought not to play a key role in tumorigenesis and thus fell from favor in the literature. We sought to determine whether subpopulations of hypoxic cancer cells have different metabolic phenotypes and gene-expression profiles that could influence tumorigenicity and therapeutic response, and we therefore developed a dual fluorescent protein reporter, HypoxCR, that detects hypoxic [hypoxia-inducible factor (HIF) active] and/or cycling cells. Using HEK293T cells as a model, we identified four distinct hypoxic cell populations by flow cytometry. The non-HIF/noncycling cell population expressed a unique set of genes involved in mitochondrial function. Relative to the other subpopulations, these hypoxic "non-Warburg" cells had highest oxygen consumption rates and mitochondrial capacity consistent with increased mitochondrial respiration. We found that these respiring cells were unexpectedly tumorigenic, suggesting that continued respiration under limiting oxygen conditions may be required for tumorigenicity.

Effects of several acetylated chitooligosaccharides on antioxidation, antiglycation and NO generation in erythrocyte.

Three kinds of chitooligosaccharides (COS) with different degrees of deacetylation were prepared and named MD90, MD70 and MD50, respectively. Antioxidation, antiglycation and nitric oxide (NO) promotion in erythrocyte of these samples were investigated. The results showed that COS, especially MD90 had obviously inhibitory effects on oxidation and glycation. In addition, MD90 displayed stronger effect on increasing endogenous NO content than both MD70 and MD50, whose degrees of deacetylation were lower. The results indicated that amino group in COS has a certain effect on the activities of COS. As COS have a conformed activity to treat diabetes, the results of this study may be meaningful for further understanding the mechanism of the action.

Biochar-derived organic carbon promoting the dehydrochlorination of 1,1,2,2-tetrachloroethane and its molecular size effects: Synergies of dipole-dipole and conjugate bases.

The environmental effects of biochar-derived organic carbon (BDOC) have attracted increasing attention. Nevertheless, it is unknown how BDOC might affect the natural attenuation of widely distributed chloroalkanes (e.g., 1,1,2,2-tetrachloroethane (TeCA)) in aqueous environments. We firstly observed that the kinetic constants (ke) of TeCA dehydrochlorination in the presence of BDOC samples or their different molecular size fractions (<1 kDa, 1∼10 kDa, and >10 kDa) ranged from 9.16×103 to 26.63×103 M-1h-1, which was significantly greater than the ke (3.53×103 M-1h-1) of TeCA dehydrochlorination in the aqueous solution at pH 8.0, indicating that BDOC samples and their different molecular size fractions all could promote TeCA dehydrochlorination. For a given BDOC sample, the kinetic constants (ke) of TeCA dehydrochlorination in the initial pH 9.0 solution was 2∼3 times greater than that in the initial pH 8.0 solution due to more formation of conjugate bases. Interestingly, their DOC concentration normalized kinetic constants (ke/[DOC]) were negatively correlated with SUVA254, and positively correlated with A220/A254 and the abundance of aromatic protein-like/polyphenol-like matters. A novel mechanism was proposed that the CH dipole of BDOC aliphatic structure first bound with the CCl dipole of TeCA to capture the TeCA molecule, then the conjugate bases (-NH-/-NH2 and deprotonated phenol-OH of BDOC) could attack the H atom attached to the ß-C atom of bound TeCA, causing a CCl bond breaking and the trichloroethylene formation. Furthermore, a fraction of >1 kDa had significantly greater ke/[DOC] values of TeCA dehydrochlorination than the fraction of <1 kDa because >1 kDa fraction had higher aliphiticity (more dipole-dipole sites) as well as more N-containing species and aromatic protein-like/polyphenol-like matters (more conjugate bases). The results are helpful for profoundly understanding the BDOC-mediated natural attenuation and fate change of chloroalkanes in the environment.