Duplicated paralog of sulfide: quinone oxidoreductase contributes to the adaptation to hydrogen sulfide-rich environment in the hydrothermal vent crab, Xenograpsus testudinatus.

The hydrothermal crab, Xenograpsus testudinatus (xtcrab) inhabits shallow-water, hydrogen sulfide (H2S)-rich hydrothermal vent regions. Until now, the adaptative strategy of xtcrab to this toxic environment was unknown. Herein, we investigated the sulfide tolerance and detoxification mechanisms of xtcrabs collected in their high-sulfide hydrothermal vent habitat. Experimental immersion of xtcrab in various sulfide concentrations in the field or in aquaria assessed its high sulfide tolerance. HPLC measurement of hemolymph sulfur compounds highlighted xtcrab detoxification capacity via catabolism of sulfide into much less toxic thiosulfate. We focused on a key enzyme for H2S detoxification, sulfide: quinone oxidoreductase (SQR). Cloning and phylogenetic analysis revealed two SQR paralogs in xtcrab, that we named xtSQR1 and xtSQR2. As shown by qPCR, xtSQR2 and xtSQR1 were expressed in the digestive gland, suggesting the involvement of both paralogs in the detoxification of food-related H2S. In contrast, xtSQR1 transcript was highly expressed in the gill, while xtSQR2 was not detectable, suggesting a specific role of SQR1 in gill detoxification of H2S of environmental origin. Comparison between xtcrabs in their hydrogen sulfide-rich hydrothermal habitat, and xtcrabs maintained for one month in sulfide-free seawater aquarium, showed higher transcript levels of gill xtSQR1 in sulfide-rich habitat, further supporting the specific role of xtSQR1 paralog in environmental H2S detoxification in the gill. Gill SQR protein level as measured by Western blot, and gill SQR enzyme activity were also higher in sulfide-rich habitat. Immunohistochemical staining further showed that SQR expression was co-localized with Na+/K+-ATPase-positive epithelial and pillar cells of the gill filament. This is the first evidence of duplicate SQR genes in crustaceans. Overall, our study suggests that the subfunctionalization of duplicate xtSQR genes may play an important role in sulfide detoxification to maintain the sulfide homeostasis in X. testudinatus, providing an ecophysiological basis for its adaptation to the high-sulfide hydrothermal vent environment.

Cellular mechanisms underlying extraordinary sulfide tolerance in a crustacean holobiont from hydrothermal vents.

The shallow-water hydrothermal vent system of Kueishan Island has been described as one of the world's most acidic and sulfide-rich marine habitats. The only recorded metazoan species living in the direct vicinity of the vents is Xenograpsus testudinatus, a brachyuran crab endemic to marine sulfide-rich vent systems. Despite the toxicity of hydrogen sulfide, X. testudinatus occupies an ecological niche in a sulfide-rich habitat, with the underlying detoxification mechanism remaining unknown. Using laboratory and field-based experiments, we characterized the gills of X. testudinatus that are the major site of sulfide detoxification. Here sulfide is oxidized to thiosulfate or bound to hypotaurine to generate the less toxic thiotaurine. Biochemical and molecular analyses demonstrated that the accumulation of thiosulfate and hypotaurine is mediated by the sodium-independent sulfate anion transporter (SLC26A11) and taurine transporter (Taut), which are expressed in gill epithelia. Histological and metagenomic analyses of gill tissues demonstrated a distinct bacterial signature dominated by Epsilonproteobacteria. Our results suggest that thiotaurine synthesized in gills is used by sulfide-oxidizing endo-symbiotic bacteria, creating an effective sulfide-buffering system. This work identified physiological mechanisms involving host-microbe interactions that support life of a metazoan in one of the most extreme environments on our planet.

Long-term psychiatric outcomes in youth with enterovirus A71 central nervous system involvement.

Long-term neurological and neurodevelopmental sequelae are a concerning issue for people with Enterovirus A71 (EV-A71) central nervous system (CNS) infection. Unfortunately, no longitudinal prospective clinical study has systematically investigated the consequences of EV-A71 CNS infection during early life on the later development of other psychiatric disorders. In this naturalistic longitudinal follow-up design, we followed forty-three youth, who got EV-A71 CNS involvement 6-18 years ago and were enrolled in other EV-A71 clinical studies then. Their psychiatric presentation, emotional/behavioral problems, and cognitive issues were examined using a psychiatrist-conducted diagnostic interview, parent- and self-rated questionnaires, and neuropsychological tests, respectively. We compared the prevalence of psychiatric disorders in youth with EV-A71 CNS involvement to a nationally representative cohort. Emotion/behavior and cognition in EV-A71-CNS-infected youth were compared to those in a matched community-based sample of healthy controls and youth with attention-deficit/hyperactivity disorder (ADHD). Compared to a national sample (absolute ADHD prevalence 10.1%), youth with EV-A71 CNS involvement had three times the odds of receiving an ADHD diagnosis (standardized prevalence ratio, 95% CI = 1.8, 4.2; absolute ADHD prevalence 34.9%). No other psychiatric diagnoses were more common in EV-A71-CNS-infected youth. Compared to community-based ADHD youth, EV-A71-CNS-infected youth with psychiatric disorders showed comparable core ADHD symptoms, opposition/defiance, autistic features, and suboptimal sustained attention performance (based on the Conners' Continuous Performance Test), all of which were more severe than healthy controls. EV-A71-CNS-infected youth without psychiatric disorders showed comparable autistic features to EV-A71-CNS-infected youth with psychiatric disorders and ADHD youth. EV-A71 CNS involvement may cause long-term, adverse psychiatric outcomes that develop into an ADHD diagnosis alongside social/communication/emotion problems and autistic features. We recommend earlier identification and intervention of these problems among these children.

A chemical probe inhibitor targeting STAT1 restricts cancer stem cell traits and angiogenesis in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is a worldwide cancer with rising annual incidence. New medications for patients with CRC are still needed. Recently, fluorescent chemical probes have been developed for cancer imaging and therapy. Signal transducer and activator of transcription 1 (STAT1) has complex functions in tumorigenesis and its role in CRC still needs further investigation. METHODS: RNA sequencing datasets in the NCBI GEO repository were analyzed to investigate the expression of STAT1 in patients with CRC. Xenograft mouse models, tail vein injection mouse models, and azoxymethane/dextran sodium sulfate (AOM/DSS) mouse models were generated to study the roles of STAT1 in CRC. A ligand-based high-throughput virtual screening approach combined with SWEETLEAD chemical database analysis was used to discover new STAT1 inhibitors. A newly designed and synthesized fluorescently labeled 4',5,7-trihydroxyisoflavone (THIF) probe (BODIPY-THIF) elucidated the mechanistic actions of STAT1 and THIF in vitro and in vivo. Colonosphere formation assay and chick chorioallantoic membrane assay were used to evaluate stemness and angiogenesis, respectively. RESULTS: Upregulation of STAT1 was observed in patients with CRC and in mouse models of AOM/DSS-induced CRC and metastatic CRC. Knockout of STAT1 in CRC cells reduced tumor growth in vivo. We then combined a high-throughput virtual screening approach and analysis of the SWEETLEAD chemical database and found that THIF, a flavonoid abundant in soybeans, was a novel STAT1 inhibitor. THIF inhibited STAT1 phosphorylation and might bind to the STAT1 SH2 domain, leading to blockade of STAT1-STAT1 dimerization. The results of in vitro and in vivo binding studies of THIF and STAT1 were validated. The pharmacological treatment with BODIPY-THIF or ablation of STAT1 via a CRISPR/Cas9-based strategy abolished stemness and angiogenesis in CRC. Oral administration of BODIPY-THIF attenuated colitis symptoms and tumor growth in the mouse model of AOM/DSS-induced CRC. CONCLUSIONS: This study demonstrates that STAT1 plays an oncogenic role in CRC. BODIPY-THIF is a new chemical probe inhibitor of STAT1 that reduces stemness and angiogenesis in CRC. BODIPY-THIF can be a potential tool for CRC therapy as well as cancer cell imaging.

Cannabinoids orchestrate cross-talk between cancer cells and endothelial cells in colorectal cancer.

Medical marijuana has been approved by the FDA for treating chemotherapy-induced nausea and vomiting. However, less is known about its direct effects on tumor cells and the tumor microenvironment. In this study, RNA-sequencing datasets in the NCBI GEO repository were first analyzed; upregulation of cannabinoid receptors was observed in both primary and metastatic colorectal cancer (CRC) tumor tissues. An increase of cannabinoid receptors was also found in patients with CRC, azoxymethane/dextran sulfate sodium-induced CRC and CRC metastatic mouse models. Δ9-Tetrahydrocannabinol (Δ9-THC)-induced tumor progression in both primary and metastatic mouse models and also increased angiogenesis. A human growth factor antibody array indicated that Δ9-THC promoted the secretion of angiogenic growth factors in CRC, leading to the induction of tube formation and migration in human-induced pluripotent stem cell-derived vascular endothelial cells. The nuclear translocation of STAT1 played important roles in Δ9-THC-induced angiogenesis and tumor progression. Pharmacological treatment with STAT1 antagonist or abrogation of STAT1 with CRISPR/Cas9-based strategy rescued those effects of Δ9-THC in CRC. This study demonstrates that marijuana might increase the risk of CRC progression and that inhibition of STAT1 is a potential strategy for attenuating these side effects.

Antiobesity Efficacy of Quercetin-Rich Supplement on Diet-Induced Obese Rats: Effects on Body Composition, Serum Lipid Profile, and Gene Expression.

The antiobesity effects of quercetin-rich supplement (QRS), which contain quercetin, lycopene, taurine, and litchi flower extract, on a high-fat diet (HFD)-induced obese rats were investigated. The rats that consume HFD with QRS (185 mg/kg rat) have significantly modulated the final body weights [490 ± 11 (HFD) → 441 ± 11 (HFD+QRS) g], total body fat [112.9 ± 4.5 (HFD) → 86.6 ± 5.7 (HFD+QRS) g], liver weights [14.8 ± 0.4 (HFD) → 12.6 ± 0.4 (HFD+QRS) g/rat], and the serum TG [102.5 ± 7.3 (HFD) → 90.7 ± 6.5 (HFD+QRS) mg/dL] to a level that resembled the regular diet-consumed rats (p < 0.05). The excretion of lipid in the faeces augmented in QRS groups as compared with the nonsupplemented HFD group [faecal total lipid: 62.43 ± 2.80 (HFD) → 73.15 ± 0.88 (HFD+QRS) mg/g dried faeces, p < 0.05]. In the histological analysis, quercetin-rich formulation supplemented groups presented a much less lipid accumulation and smaller size of adipocytes. Moreover, a decreased serum thiobarbituric acid reactive substances [1.55 ± 0.17 (HFD) → 0.78 ± 0.04 (HFD+QRS) nmol MDA eq/mL serum] increased levels of serum Trolox equivalent antioxidant capacity [3.89 ± 0.08 (HFD) → 6.46 ± 0.20 (HFD+QRS) µmol/mL serum], and more active hepatic antioxidant enzymes were observed in the supplemented groups (p < 0.05). The result of this work is a good demonstration of how a combination of bioactive compounds could work synergistically and become very effective in disease prevention.

Efficacy of two different materials used in auricular acupressure on weight reduction and abdominal obesity.

The current study was designed to test the efficacy of different materials used in an auricular acupressure program on weight reduction, changes to waist circumference and waist-to-hip ratio. This study used a randomized design with two groups who were treated with auricular acupressure using Semen Vaccariae or the Japanese Magnetic Pearl. Both groups consisted of Asian young adults with a waist circumference ≥ 80 cm in the females and ≥ 90 cm in the males. At completion of the eight-week treatment period, the total sample size was 56 young adults who ranged in age from 18 to 20 years old. Each participant was met with weekly for ten-minute sessions during which ear acupressure treatment was performed. Sessions continued for eight weeks wherein both groups received acupressure with the Japanese Magnetic Pearl or Semen Vaccariae on the ear acupoints. While both groups showed significant reductions (p ≤ 0.05) to body weight and waist circumference after eight weeks of treatments, the group treated with Semen Vaccariae group showed a more effective weight loss over the short term. Given that auricular acupressure is a safe and cost-effective treatment for weight loss, our results suggest that auricular acupressure is a reasonable option for the treatment of overweight and obesity in young adults.

Effects of auricular acupressure on weight reduction and abdominal obesity in Asian young adults: a randomized controlled trial.

The current study was designed to test the efficacy of auricular acupressure on weight reduction and changes of waist circumference and waist-to-hip ratio. This study used a randomized design with one control group and one experimental group consisting of Asian young adults with a waist circumference ≥80 cm in the females and ≥90cm in the males. At completion of eight weeks of auricular therapy, the total sample size was 55 young adults who ranged in age from 18 to 20 years old. Each participant was treated weekly for ear acupressure in ten-minute sessions. Sessions continued for eight weeks wherein the control group received acupressure only while the experimental group received acupressure with the Japanese Magnetic Pearl on the ear acupoints. While both the control and treatment groups showed significant reduction (p ≤ 0.05) to body weight and waist circumference after eight weeks of treatment, only the group treated with Japanese Magnetic Pearls showed decreased waist to hip ratio. Thus, auricular acupressure may be a beneficial addition to weight loss programs for young adults. Auricular acupressure is thus a reasonable option in the treatment of overweight and obesity in young adults.

[The decision making process of adolescent pregnant women receiving help from Taipei single mother assistance centers].

This research explores the problem of teenage pregnancy through the experiences of individuals receiving help from two single-mother assistance centers in Taipei, Taiwan. In particular, this study attempts to understand the difficult thought processes undergone by these young women from the time that they became aware of their pregnancy to the point at which they decided to carry their baby to term. Grounded theory was employed in designing this research. A total of 10 teenage subjects were involved in this study. After analyzing data, findings were made in the following four core areas: (1) The process through which teenage girls decide to take their unborn babies to term; (2) Feelings of isolation and reaching out for help; (3) The social and cultural pressures faced by single teenage girls who decide to have children out of wedlock; and (4) The self-revival and renewal of teenage girls' beliefs. Through this study, we can better understand the processes and experiences of single teenagers from their initial comprehension of their pregnancy through to the decision to take their pregnancy to term.

Neonatal isolation accelerates the developmental switch in the signalling cascades for long-term potentiation induction.

The molecular mechanisms underlying long-term potentiation (LTP) in the CA1 region of the hippocampus are known to vary with developmental age. The physiological factors regulating this developmental change, however, have not yet been elucidated. Here we show that mild neonatal isolation accelerates the developmental switch in the signalling cascades for hippocampal CA1 LTP induction from a cyclic AMP-dependent protein kinase (PKA)- to a Ca2(+)/calmodulin-dependent protein kinase II (CaMKII)-dependent pattern via the activation of the corticotrophin-releasing factor (CRF) system. Furthermore, this action appears to be mediated through an increased transcription of the alpha isoform of the CaMKII (CaMKIIalpha) gene. We also demonstrate that application of CRF to cultured hippocampal neurones significantly increases the expression of CaMKIIalpha, which is blocked by the non-specific CRF receptor antagonist astressin, the specific CRF receptor 1 antagonist NBI 27911, and the PKA inhibitor KT5720, but not by the CRF receptor 2 antagonist K 41498, or the protein kinase C inhibitor, bisindolylmaleimide I. CRF signalling also mediates the normal maturation of LTP. These results suggest a novel role for CRF in regulating early developmental events in the hippocampus, and indicate that, although maternal deprivation is stressful for the neonate, appropriate neonatal isolation can serve to promote an endocrine state that fosters the rate of maturation of the signalling cascades underlying the induction of LTP in the developing hippocampus.