Hepatic IGF2/H19 Epigenetic Alteration Induced Glucose Intolerance in Gestational Diabetes Mellitus Offspring via FoxO1 Mediation.

Objective: The offspring of women with gestational diabetes mellitus (GDM) have a high predisposition to developing type 2 diabetes during childhood and adulthood. The aim of the study was to evaluate how GDM exposure in the second half of pregnancy contributes to hepatic glucose intolerance through a mouse model. Methods: By creating a GDM mouse model, we tested glucose and insulin tolerance of offspring by intraperitoneal glucose tolerance test (IPGTT), insulin tolerance test (ITT), and pyruvate tolerance test (PTT). In addition, we checked the expression of genes IGF2/H19, FoxO1, and DNMTs in the mouse liver by RT-qPCR. Pyrosequencing was used to detect the methylation status on IGF2/H19 differentially methylated regions (DMRs). In vitro insulin stimulation experiments were performed to evaluate the effect of different insulin concentrations on HepG2 cells. Moreover, we detect the interaction between FoxO1 and DNMT3A by chromatin immunoprecipitation-quantitative PCR (Chip-qPCR) and knock-down experiments on HepG2 cells. Results: We found that the first generation of GDM offspring (GDM-F1) exhibited impaired glucose tolerance (IGT) and insulin resistance, with males being disproportionately affected. In addition, the expression of imprinted genes IGF2 and H19 was downregulated in the livers of male mice via hypermethylation of IGF2-DMR0 and IGF2-DMR1. Furthermore, increased expression of transcriptional factor FoxO1 was confirmed to regulate DNMT3A expression, which contributed to abnormal methylation of IGF2/H19 DMRs. Notably, different insulin treatments on HepG2 demonstrated those genetic alterations, suggesting that they might be induced by intrauterine hyperinsulinemia. Conclusion: Our results demonstrated that the intrauterine hyperinsulinemia environment has increased hepatic FoxO1 levels and subsequently increased expression of DNMT3A and epigenetic alterations on IGF2/H19 DMRs. These findings provide potential molecular mechanisms responsible for glucose intolerance and insulin resistance in the first male generation of GDM mice.

Relationships among Affect, Hardiness and Self-Efficacy in First Aid Provision by Airline Cabin Crew.

Cabin crews being first responders, passengers' health assurance is also one of their main responsibilities. This study explored the association among first aid affect, work-related hardiness and self-efficacy of first aid, as well as the mediation role of work-related hardiness in airline cabin crews. Three self-reporting instruments were applied in this study: one was the first aid affect questionnaire, the second was a work-related hardiness questionnaire, the third was self-efficacy of the first aid questionnaire. Data were collected from 525 cabin crew members across five airlines in Taiwan (480 females and 45 males). The results showed that both exploratory and confirmatory factor analyses indicated that three instruments had satisfactory validity and reliability. Positive significant relationships were found among cabin crews' first aid affect, work-related hardiness and self-efficacy of first aid. Cabin crews' commitment dimension of work-related hardiness turned out to be positively related to self-efficacy of first aid. In addition, the results of the study also revealed that cabin crews' work commitment plays a mediating role between their first aid affect and self-efficacy of first aid. To enhance the self-efficacy of first aid, it is necessary for the airlines to strengthen cabin crews' work commitment. Furthermore, fostering cabin crews' first aid affect is also one an important training goal.

All-optical reversible single-photon isolation at room temperature.

Nonreciprocal devices operating at the single-photon level are fundamental elements for quantum technologies. Because magneto-optical nonreciprocal devices are incompatible for magnetic-sensitive or on-chip quantum information processing, all-optical nonreciprocal isolation is highly desired, but its realization at the quantum level is yet to be accomplished at room temperature. Here, we propose and experimentally demonstrate two regimes, using electromagnetically induced transparency (EIT) or a Raman transition, for all-optical isolation with warm atoms. We achieve an isolation of 22.52 ± 0.10 dB and an insertion loss of about 1.95 dB for a genuine single photon, with bandwidth up to hundreds of megahertz. The Raman regime realized in the same experimental setup enables us to achieve high isolation and low insertion loss for coherent optical fields with reversed isolation direction. These realizations of single-photon isolation and coherent light isolation at room temperature are promising for simpler reconfiguration of high-speed classical and quantum information processing.

Elevated Expression of lncRNA MEG3 Induces Endothelial Dysfunction on HUVECs of IVF Born Offspring via Epigenetic Regulation.

Cardiovascular dysfunction in children born after in vitro fertilization (IVF) has been of great concern, the potential molecular mechanisms for such long-term outcomes are still unknown. Here, we found that systolic blood pressure was a little higher in IVF born offspring at 2 years old compared to those born after being naturally conceived. Besides, the expression level of maternally expressed gene 3 (MEG3) was higher in human umbilical vein endothelial cells (HUVECs) from IVF offspring than that in spontaneously born offspring. Pearson correlation test showed that MEG3 relative expression is significantly related to the children's blood pressure (Coefficient = 0.429, P = 0.0262). Furthermore, we found decreased expression of endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) along with elevated expression of endothelial-1(ET1) in HUVECs from IVF offspring, accompanied by lower secretion of nitrite, VEGF, and higher secretion of ET1 in the umbilical cord serum of IVF offspring. Correlation analysis showed MEG3 expression highly correlated with ET1 and Nitrate concentration. With pyrosequencing technology, we found that elevated expression of MEG3 was the result of hypomethylation of the MEG3 promoter. Therefore, our results provide a potential mechanism addressing the high-risk of hypertension in IVF offspring via MEG3 epigenetic regulation.

Confounded by obesity and modulated by urinary uric acid excretion, sleep-disordered breathing indirectly relates to hyperuricaemia in males: A structural equation model.

Sleep-disordered breathing (SDB) causes hypoxic stress and can trigger uric acid (UA) overproduction. We comprehensively investigated whether SDB, interacting with components of metabolic syndrome, hepatic and renal dysfunctions, low physical fitness, sedentary lifestyle, disrupted sleep, and chronic systemic inflammation (CSI), is directly associated with hyperuricaemia. In 528 community-based males (mean [SD] age 46.2 [7.4] years), we cross-sectionally analysed measures of anthropometry; self-reported lifestyle habits; overnight sleep polysomnography data; cardiopulmonary exercise tests; and biomarkers of cardiometabolic, hepatic, and renal functions; and CSI, using structural equation modelling. Objective disrupted sleep, C-reactive protein, low physical fitness, and sedentary lifestyle were not related to UA levels in univariate analysis and were excluded. The latent variables (with corresponding manifest variables) obesity (body mass index, waist-hip ratio), hypertension (post-sleep systolic, diastolic blood pressure), dyslipidaemia (total cholesterol, triglyceride/high-density lipoprotein cholesterol), hepatic dysfunction (alanine aminotransferase, aspartate transaminase), and renal dysfunction (blood urea nitrogen, serum creatinine) were positively; and hyperglycaemia (fasting glucose, glycated haemoglobin) was negatively associated with hyperuricaemia (serum UA), except for SDB (Apnea-Hypopnea Index, percentage of oxygen saturation <90% period against total sleep time, oxygen desaturation index) in the one-stage influence model. In the two-stage model, SDB, closely interacting with obesity, was positively indirectly associated with hyperuricaemia through directly linked renal dysfunction and obesity-linked hypertension, inverse hyperglycaemia, dyslipidaemia, and hepatic dysfunction. In conclusion, structural equation modelling reveals that SDB closely interacts with obesity and is positively but indirectly related to hyperuricaemia in males. This suggests that urinary UA excretion modulates and obesity confounds the SDB-hyperuricaemia relationship.

Entangled qutrits generated in four-wave mixing without post-selection.

High-dimensional entangled states and quantum repeaters are important elements in efficient long-range quantum communications. The high-dimensional property associated with the orbital angular momentum (OAM) of each photon improves the bandwidth of the quantum communication network. However, the generation of high-dimensional entangled states by the concentration method reduces the brightness of the entangled light source, making extensions to these higher dimensions difficult. To overcome this difficulty, we propose to generate entangled qutrits in the OAM space by loading the pump light with OAM. Compared with the concentration method, our experimental results show that the rate of generation of photon pairs improves significantly with an observed 5.5-fold increase. The increased generation rate provides the system with the ability to resist the noise and improve the fidelity of the state. The S value of the Clauser-Horne-Shimony-Holt inequality increases from 2.48 ± 0.07 to 2.69 ± 0.04 under the same background noise, and the fidelity of the reconstructed density matrix improves from 57.8 ± 0.14% to 70 ± 0.17%. These achievements exhibit the enormous advantages of high-dimensional entanglement generation.

Experimental realization of optical storage of vector beams of light in warm atomic vapor.

Vector beams have drawn considerable interest recently because of their unique properties in the transverse plane. Here we experimentally realize optical storage of a vector beam of light in a warm cell. The vector beam is tailored using a Sagnac interferometer containing an internal vortex phase plate, and the light pulse is stored in warm rubidium vapor. The preservation of both the spatial structure and the phase information is verified after retrieval. The implementation of vector beam storage in a room-temperature memory has potential for use in the fabrication of versatile vortex-based quantum networks.

Hypermethylation of delta-like homolog 1/maternally expressed gene 3 loci in human umbilical veins: insights into offspring vascular dysfunction born after preeclampsia.

BACKGROUND: Increasing epidemiological studies have confirmed the association between maternal preeclampsia and elevated blood pressure in their offspring. Though case-control or cohort studies have demonstrated long-term outcomes for the offspring of preeclampsia, it is still a question that how these changes were caused by genetic reasons or by preeclampsia itself. OBJECTIVE: In our study, we explored the potential epigenetic regulation of delta-like homolog 1-maternally expressed gene 3 (DLK1-MEG3) region in human umbilical vein endothelial cells (HUVECs), and its connection with endothelium-derived factors. STUDY DESIGN: We recruited 58 singletons born with spontaneous conception (control group) and 67 singletons whose mother with preeclampsia (preeclampsia group), and detected the infants' blood pressure and growth development index. To explore the potential mechanism, we did real-time PCR to test DLK1-MEG3 imprinted genes and endothelium-derived factors. ELISA confirmed the protein secretion changes between two groups. In addition to confirm epigenetic alteration in preeclampsia HUVEC, we performed pyro-sequencing to detect methylation status of two different methylation regions: intergenic differential methylation region (IG-DMR) and MEG3 DMR which control the expression of DLK1 and MEG3. Furthermore, Person correlation was used to make sure the association of methylation alteration of IG-DMR and endothelium-derived factors. RESULTS: In our study, we found that DBP was significantly lower in preeclampsia offspring who born over 34 weeks compared with normal offspring (53.59 ±â€Š1.38 vs. 59.9 ±â€Š1.40 mmHg, P < 0.01), which leads to higher pulse pressure difference. Quantitative real-time PCR showed that imprinted gene DLK1 level significantly increased and MEG3 level decreased in HUVEC of preeclampsia group compared with control group, accompanying with lower expression of endothelial nitric oxide synthase and vascular endothelial growth factor (VEGF), higher expression of endothelin-1 (ET1), which are close related with vascular endothelial function. Meanwhile, ELISA assay of ET1, nitrite, VEGF were consistent with real-time results. Furthermore, abnormal expression of DLK1-MEG3 expression was caused by hypermethylation status of IG-DMR, And methylation status of IG-DMR highly correlated with ET1 concentration and nitrate concentration, these might be one of the mechanisms for impaired endothelial function (coefficient = 0.5806, P = 0.0115; coefficient = -0.4883, P = 0.0398). CONCLUSION: Our results demonstrated that altered expression of imprinted genes DLK1 and MEG3 were caused by hypermethylation of IG-DMR in HUVEC of preeclampsia group, accompanied by lower secretion of nitrite, VEGF, and higher secretion of ET1. It might be one potential mechanism for higher risk of cardiovascular disease in preeclampsia offspring later in life.

Intrauterine hyperglycemia induces intergenerational Dlk1-Gtl2 methylation changes in mouse placenta.

An intrauterine hyperglycemic environment has long-lasting effects on the offspring. Recent studies focused on fetal tissues, whereas we studied the development and molecular alteration of the placenta. By intercrossing male and female adult control (C) and first-generation offspring mice with gestational diabetes mellitus (F1-GDM), we obtained four groups of second generation (F2) offspring: 1) C♂-C♀, 2) C♂-GDM♀, 3) GDM♂-C♀, 4) GDM♂- GDM♀. Placental weights in F1-GDM offspring were lower than in the control group. Placental weights in F2-offspring decreased through the paternal line. Placental RNA was extracted and analyzed using microarrays on day18.5 of pregnancy. This revealed 35 upregulated imprinted genes and 10 down-regulated imprinted genes. Dlk1and Gtl2 were especially down-regulated and up-regulated, respectively, due to their abnormal methylation status. These findings suggest that intrauterine hyperglycemia decreased placental weight in the first generation, and this was transmitted paternally to the second generation in mice. They also suggest intrauterine hyperglycemia leads to abnormal placental Dlk1-Gtl2 expression due to DNA methylation in first and second generation mice.

Experimental realization of narrowband four-photon Greenberger-Horne-Zeilinger state in a single cold atomic ensemble.

Multi-photon entangled states not only play a crucial role in research on quantum physics but also have many applications in quantum information fields such as quantum computation, quantum communication, and quantum metrology. To fully exploit the multi-photon entangled states, it is important to establish the interaction between entangled photons and matter, which requires that photons have narrow bandwidth. Here, we report on the experimental generation of a narrowband four-photon Greenberger-Horne-Zeilinger state with a fidelity of 64.9% through multiplexing two spontaneous four-wave mixings in a cold Rb85 atomic ensemble. The full bandwidth of the generated GHZ state is about 19.5 MHz. Thus, the generated photons can effectively match the atoms, which are very suitable for building a quantum computation and quantum communication network based on atomic ensembles.

Construction of a Multi-Cage-Based MOF with a Unique Network for Efficient CO2 Capture.

As a kind of MOFs, cage-based MOFs usually carry large voids and small windows, which are advantageous to the storage of small molecules that remain kinetically trapped inside the cages (confinement effect). By adjusting the size of windows via reticular synthesis, the cage-based MOFs can selectively capture and separate the suitable size molecules. Here, considering angle-directed and face-directed strategies, a novel multicage-based MOF NUM-3 with a new (3,4,5)-connected topology was successfully constructed in the mixed-ligands assembly. In the framework of NUM-3, there exist four different kinds of cages, which exhibit diverse polyhedral configurations. The four kinds of cages in the order ABCDDCBA as the minimum repeat unit form a 1D tortuous channel along the c axis. Based on the structure characteristics that the 1D channel exhibits different inner diameter (from 4.0 to13.0 Å), NUM-3a (actived NUM-3) can capture CO2 over C2H4 and C2H6 by the size selectivity (the empirical kinetic diameters: CO2 < C2H4 < C2H6). In addition, it also exhibits commendable selectivity for CO2 over N2 and CH4.

Can retrohepatic tunnel be quickly and easily established for laparoscopic liver hanging maneuver by Goldfinger dissector in laparoscopic right hepatectomy?

OBJECTIVE: The liver hanging maneuver (LHM) is rarely applied in laparoscopic right hepatectomy (LRH) because of the difficulty encountered in retrohepatic tunnel (RT) dissection and tape positioning. Thus far no report has detailed how to quickly and easily establish RT for laparoscopic LHM in LRH, nor has employment of the Goldfinger dissector to create a total RT been reported. This study's aim was to evaluate the safety and feasibility of establishing RT for laparoscopic LHM using the Goldfinger dissector in LRH. METHODS: Between March 2015 and July 2015, five consecutive patients underwent LRH via the caudal approach with laparoscopic LHM. A five-step strategy using the Goldfinger dissector to establish RT for laparoscopic LHM was adopted. Perioperative data were analyzed. RESULTS: The median age of patients was 58 (range, 51-65) years. Surgery was performed for one intrahepatic lithiasis and four hepatocellular carcinomas with a median size of 90 (40-150) mm. The median operative time was 320 (282-358) min with a median blood loss of 200 (200-600) ml. Laparoscopic LHM was achieved in a median of 31 (21-62) min, and the median postoperative hospital stay was 14 (9-16) d. No transfusion or conversion was required, and no severe liver-related morbidity or death was observed. CONCLUSIONS: The Goldfinger dissector is a useful instrument for the establishment of RT. A five-step strategy using the Goldfinger dissector can quickly and easily facilitate an RT for a laparoscopic LHM in LRH.

Seat surface inclination may affect postural stability during Boccia ball throwing in children with cerebral palsy.

The aim of the study was to examine how seat surface inclination affects Boccia ball throwing movement and postural stability among children with cerebral palsy (CP). Twelve children with bilateral spastic CP (3 with gross motor function classification system Level I, 5 with Level II, and 4 with Level III) participated in this study. All participants underwent pediatric reach tests and ball throwing performance analyses while seated on 15° anterior- or posterior-inclined, and horizontal surfaces. An electromagnetic motion analysis system was synchronized with a force plate to assess throwing motion and postural stability. The results of the pediatric reach test (p = 0.026), the amplitude of elbow movement (p = 0.036), peak vertical ground reaction force (PVGRF) (p < 0.001), and movement range of the center of pressure (COP) (p < 0.020) were significantly affected by seat inclination during throwing. Post hoc comparisons showed that anterior inclination allowed greater amplitude of elbow movement and PVGRF, and less COP movement range compared with the other inclines. Posterior inclination yielded less reaching distance and PVGRF, and greater COP movement range compared with the other inclines. The anterior-inclined seat yielded superior postural stability for throwing Boccia balls among children with bilateral spastic CP, whereas the posterior-inclined seat caused difficulty.

Motion analysis of throwing Boccia balls in children with cerebral palsy.

Boccia is a sport suitable for children with cerebral palsy (CP). Throwing Boccia balls requires upper extremity and torso coordination. This study investigated the differences between children with CP and normally developed children regarding throwing patterns of Boccia balls. Thirteen children with bilateral spastic CP and 20 normally developed children participated in this study. The tests in this study were a pediatric reach test and throwing of Boccia balls. A 3D electromagnetic motion tracking system and a force plate were synchronized to record and analyze biomechanical parameters of throwing Boccia balls. The results of the pediatric reach test for participants with CP were significantly worse than those for normally developed participants. The 2 groups of participants did not significantly differ regarding the distance between a thrown Boccia ball and a target ball (jack). Participants with CP demonstrated significantly longer movement duration, smaller amplitude of elbow movement, greater amplitudes of shoulder abduction and flexion, slower maximal velocity of torso flexion and the linear velocity of moving the wrist joint forward, faster maximal velocity of head flexion, and smaller sway ratio compared with normally developed participants when throwing Boccia balls. Participants with CP seemed to mainly use head and shoulder movements to bring the Boccia balls forward with limited torso movement. Normally developed participants brought the Boccia ball forward with faster torso and greater elbow movement while stabilizing head and shoulder movements. Nevertheless, participants with CP did not demonstrate significantly worse performance in the throwing accuracy of Boccia balls.

Repair of bile duct defect with degradable stent and autologous tissue in a porcine model.

AIM: To introduce and evaluate a new method to repair bile duct defect with a degradable stent and autologous tissues. METHODS: Eight Ba-Ma mini-pigs were used in this study. Experimental models with common bile duct (CBD) defect (0.5-1.0 cm segment of CBD resected) were established and then CBD was reconstructed by duct to duct anastomosis with a novel degradable stent made of poly [sebacic acid-co-(1,3-propanediol)-co-(1,2-propanediol)]. In addition, a vascularized greater omentum was placed around the stent and both ends of CBD. Cholangiography via gall bladder was performed for each pig at postoperative months 1 and 3 to rule out stent translocation and bile duct stricture. Complete blood count was examined pre- and post-operatively to estimate the inflammatory reaction. Liver enzymes and serum bilirubin were examined pre- and post-operatively to evaluate the liver function. Five pigs were sacrificed at month 3 to evaluate the healing of anastomosis. The other three pigs were raised for one year for long-term observation. RESULTS: All the animals underwent surgery successfully. There was no intraoperative mortality and no bile leakage during the observation period. The white blood cell counts were only slightly increased on day 14 and month 3 postoperatively compared with that before operation, the difference was not statistically significant (P = 0.652). The plasma level of alanine aminotransferase on day 14 and month 3 postoperatively was also not significantly elevated compared with that before operation (P = 0.810). Nevertheless, the plasma level of γ-glutamyl transferase was increased after operation in both groups (P = 0.004), especially 2 wk after operation. The level of serum total bilirubin after operation was not significantly elevated compared with that before operation (P = 0.227), so did the serum direct bilirubin (P = 0.759). By cholangiography via gall bladder, we found that the stent maintained its integrity of shape and was still in situ at month 1, and it disappeared completely at month 3. No severe CBD dilation and stricture were observed at both months 1 and 3. No pig died during the 3-mo postoperative observation period. No sign of necrosis, bile duct stricture, bile leakage or abdominal abscess was found at reoperation at month 3 postoperatively. Pigs had neither fragments of stent nor stones formed in the CBD. Collagen deposit was observed in the anastomosis by hematoxylin and eosin (HE) and Masson's trichrome stains. No severe cholestasis was observed in liver parenchyma by HE staining. Intestinal obstruction was found in a pig 4 mo after operation, and no bile leakage, bile duct stricture or biliary obstruction were observed in laparotomy. No sign of bile duct stricture or bile leakage was observed in the other two pigs. CONCLUSION: The novel method for repairing bile duct defect yielded a good short-term effect without postoperative bile duct stricture. However, the long-term effect should be further studied.

Experimental research of stent anastomosis of gastrojejunostomy in a porcine model.

BACKGROUND: Gastrojejunostomy is one of the most frequently used procedures for general surgeons. The creation of anastomosis between various parts of the gastrointestinal tract is a basic technical component and major task in the daily practice of almost all gastrointestinal procedures. This research evaluated a new procedure of making gastrointestinal anastomosis with stent. METHODS: Twenty experimental mini-pigs were randomized into two groups. In stent anastomosis group (SA), the anastomoses were constructed with a poly-levolactic acid stent. In hand-sewn group (HA), the anastomoses were performed with a single-layer continuous suture. Abdominal X-ray with intraluminal contrast was performed on the 10th postoperative day. Five pigs of each group were sacrificed on the postoperative days 3 and 14 to determine anastomotic bursting pressure in situ, hydroxyproline concentration, and histopathological evaluation of the anastomotic sites. RESULTS: There was no intraoperative morbidity or mortality. The median time needed for the sutured anastomosis was (21.7 ± 2.3) minutes and for the stent anastomosis was (11.9 ± 1.9) minutes (P < 0.001). Abdominal X-ray with intraluminal contrast demonstrated normal gas distribution and showed no evidence of leakage or obstruction. Macroscopic appearance at the longitudinal opening of anastomosis was always good in both groups. The median anastomotic bursting pressure was (18.2 ± 1.6) kPa in SA group on postoperative day 3, compared with (11.7 ± 3.2) kPa in HA group (P = 0.003). The anastomotic bursting pressure on day 14 was not significantly different between SA group ((27.1 ± 2.6) kPa) and HA group ((28.3 ± 1.7) kPa) (P = 0.388). The hydroxyproline concentrations were not significantly different. CONCLUSIONS: The stent anastomosis was not considered to be more difficult than a sutured anastomosis. This method is proved to be safe and feasible compared with the traditional hand-sewn method in the porcine model. The method increases early anastomotic strength in this study.