Infection by hepatitis B virus (HBV) accounts for 50-80% of hepatocellular carcinoma (HCC) development worldwide, in which the HBV-encoded X protein (HBx) has critical role in the induction of ...carcinogenesis. Several studies have shown that thyroid hormone (TH) suppresses HCC development and protects hepatocytes from HBx-induced damage, thus it is of interest to examine whether TH can protect hepatocytes from HBx-induced carcinogenesis. By treating HBx- transgenic mice with or without TH, we confirmed the protective effects of TH on HBx-induced hepatocarcinogenesis, which was achieved via reduction of reactive oxygen species (ROS) inflicted DNA damage. We further found that TH induced biogenesis of mitochondria (MITO) and autophagy of HBx-targeted MITO simultaneously, consequently leading to suppression of HBx-promoted ROS and carcinogenesis. Using microarray data analysis, this protective effect of TH was found to be mediated via activation of PTEN-induced kinase 1 (PINK1) in hepatocytes. PINK1, in turn, activated and recruited Parkin, an E3 ligase, to ubiquitinate MITO-associated HBx protein and trigger selective mitophagy. The pathological significance of the TH/PINK1 pathway in liver protection was confirmed by the concomitant decrease in expression of both TR and PINK1 in matched HCC tumor tissues and negatively correlated with aggressive progression of cancer and poor prognosis. Our data indicate that TH/PINK1/Parkin pathway has a critical role in protecting hepatocytes from HBx-induced carcinogenesis. Notably, several liver-targeting therapeutic derivatives of TH facilitating prevention or therapy of steatosis have been identified. Furthermore, our proof-of-concept experiments suggest that application of T
constitutes an effective novel therapeutic or preventive option for HCC. Thus, the utilization of the agonists of TRs could be the meaningful strategy in liver relative diseases, ranging from simple hepatic steatosis to HCC.
The aim was to compare viscoelastic properties of Achilles tendons between legs in elite athletes with unilateral tendinosis, and to investigate relationships between the properties and explosive ...performance and clinical severity. Seventeen male athletes (mean ± standard deviation age, 27.3 ± 2.0 years) who had unilateral, chronic middle‐portion tendinopathy of the Achilles tendon were assessed by the Victorian Institute of Sport Assessment questionnaire, measurements of tendon viscoelastic properties, voluntary electromechanical delay (EMD), normalized rate of force development (RFD), and one‐leg hopping distance. Compared with the non‐injured leg, the tendinopathic leg showed reduced tendon stiffness (−19.2%. P < 0.001), greater mechanical hysteresis (+21.2%, P = 0.004), lower elastic energy storage and release (−14.2%, P = 0.002 and −19.1%, P < 0.001), lower normalized RFD at one‐fourth (−16.3%, P = 0.02), 2/4 (−17.3%, P = 0.006), and three‐fourths maximal voluntary contraction (−13.7%, P = 0.02), longer soleus and medial gastrocnemius voluntary EMD (+26.9%, P = 0.009 and +24.0%, P = 0.004), and shorter hopping distances (−34.1%, P < 0.001). Tendon stiffness was correlated with normalized RFD, voluntary EMD in the medial gastrocnemius, and hopping distances (r ranged from −0.35 to 0.64, P < 0.05). Hysteresis was correlated to the soleus voluntary EMD and hopping distances (r = 0.42 and −0.39, P < 0.05). We concluded that altered tendon viscoelastic properties in Achilles tendinosis affect explosive performance in athletes.
The 3D printed bulk samples fabricated by selective laser melting (SLM) of the additive manufacturing technique are usually considered to be 3D isotropic in microstructures and mechanical responses. ...This study systematically investigates the anisotropic responses in terms of hardness and electrochemical resistance for the X-, Y- and Z-planes of the SLM Ti-6Al-4V bulk samples fabricated with the zigzag laser path strategy. Results show that all SLM planes exhibit no significant difference in Young's modulus compared to the mechanically rolled plate. However, the X-plane, referred to the cross-sectional plane perpendicular to the laser moving direction, is found ~20% lower hardness and the lowest corrosion resistance compared to the Y- and Z-planes. The underlying reasoning is researched and discussed. The microstructure observations indicate that artifact holes are induced in the X-plane due to un-uniform laser intensity distribution between two neighboring printing lines. Alternatively, the Y- and Z-planes exhibit dense morphology due to multiple heating while zigzag scanning. Experimental results also indicate that the SLM materials exhibit higher corrosion resistance than the commercial rolled materials.
Traffic emissions are a significant source of airborne particulate matter (PM) in ambient environments. These emissions contain an abundance of toxic metals and thus pose adverse effects on human ...health. Size-fractionated aerosol samples were collected from May to September 2013 by using micro-orifice uniform deposited impactors (MOUDIs). Sample collection was conducted simultaneously at the inlet and outlet sites of Hsuehshan Tunnel in northern Taiwan, which is the second-longest freeway tunnel (12.9 km) in Asia. This endeavor aims to characterize the chemical constituents and size distributions, as well as fingerprinting ratios of particulate metals emitted by vehicle fleets. A total of 36 metals in size-resolved aerosols were determined through inductively coupled plasma mass spectrometry. Three major groups – namely, tailpipe emissions (Zn, Pb, and V in fine mode), wear debris (Cu, Cd, Fe, Ga, Mn, Mo, Sb, and Sn), and resuspended dust (Ca, Mg, K, and Rb) – of airborne PM metals were categorized on the basis of the results of enrichment factor, correlation matrix, and principal component analysis. Size distributions of wear-originated metals resembled the pattern of crustal elements, which were predominated by super-micron particulates (PM1–10). By contrast, tailpipe exhaust elements such as Zn, Pb, and V were distributed mainly in submicron particles. By employing Cu as a tracer of wear abrasion, several inter-metal ratios – including Fe / Cu (14), Ba / Cu (1.05), Sb / Cu (0.16), Sn / Cu (0.10), and Ga / Cu (0.03) – served as fingerprints for wear debris. However, the data set collected in this work is useful for further studies on traffic emission inventory and human health effects of traffic-related PM.
Sirtuin deacetylases and FOXO (Forkhead box, class O) transcription factors have important roles in many biological pathways, including cancer development. SIRT1 and SIRT2 deacetylate FOXO factors to ...regulate FOXO function. Because acetylation and ubiquitination both modify the ɛ-amino group of lysine residues, we investigated whether FOXO3 deacetylation by SIRT1 or SIRT2 facilitates FOXO3 ubiquitination and subsequent proteasomal degradation. We found that SIRT1 and SIRT2 promote FOXO3 poly-ubiquitination and degradation. Proteasome-inhibitor treatment prevented sirtuin-induced FOXO3 degradation, indicating that this process is proteasome dependent. In addition, we demonstrated that E3 ubiquitin ligase subunit Skp2 binds preferentially to deacetylated FOXO3. Overexpression of Skp2 caused poly-ubiquitination of FOXO3 and degradation, whereas knockdown of Skp2 increased the amount of FOXO3 protein. We also present evidence that SCF-Skp2 ubiquitinates FOXO3 directly in vitro. Furthermore, mutating four known acetylated lysine residues (K242, K259, K290 and K569) of FOXO3 into arginines to mimic deacetylated FOXO3 resulted in enhanced Skp2 binding but with inhibition of FOXO3 ubiquitination; this suggests that some or all of these four lysine residues are likely the sites for ubiquitination. In the livers of mice deficient in SIRT1, we detected increased expression of FOXO3, indicating SIRT1 regulates FOXO3 protein levels in vivo. Furthermore, we found that the elevation of SIRT1 and Skp2 expression in malignant PC3 and DU145 prostate cells is responsible for the downregulation of FOXO3 protein levels in these cells. Taken together, our data support the notion that deacetylation of FOXO3 by SIRT1 or SIRT2 facilitates Skp2-mediated FOXO3 poly-ubiquitination and proteasomal degradation.
Metal-organic frameworks (MOFs) as solid sorbents for carbon dioxide (CO
) capture face the challenge of merging efficient capture with economical regeneration in a durable, scalable material. ...Zinc-based Calgary Framework 20 (CALF-20) physisorbs CO
with high capacity but is also selective over water. Competitive separations on structured CALF-20 show not just preferential CO
physisorption below 40% relative humidity but also suppression of water sorption by CO
, which was corroborated by computational modeling. CALF-20 has a low enthalpic regeneration penalty and shows durability to steam (>450,000 cycles) and wet acid gases. It can be prepared in one step, formed as composite materials, and its synthesis can be scaled to multikilogram batches.
This study measured the potentiation effects of plyometric training normalized electromyography (EMG) in triceps surae, stiffness and elastic energy utilization of the Achilles tendon and ...investigated the correlations between these effects and performances voluntary electromechanical delay (EMD) and jump height. Twenty‐one subjects were randomly assigned either to the control group (10 subjects: age 22.3±1.6 years) or to a training group (11 subjects: age 22.1±1.6 years) that performed 8 weeks of plyometric training. Results: As compared with the performances before training, normalized EMG in the soleus were significantly (P≤0.001) increased after 4 and 8 weeks of training. Tendon stiffness, elastic energy storage, release and jump height determined after training were significantly increased (P<0.05), with a concomitantly reduced voluntary EMD (P=0.01). These variables also showed significant differences vs the control group (all P<0.05). The other variables remained unchanged. Correlations were observed between tendon stiffness and either voluntary EMD (r=−0. 77, P=0.014) or jump height (r=0.54, P=0.031). Conclusions: Plyometric training specifically potentiated the normalized EMG, tendon stiffness and elastic energy utilization in the myotendinous complex of the triceps surae. Although these changes are possibly essential determinants, only increases of tendon stiffness were observed to correlate with performance improvements.
The recent focus on topological insulators is due to the scientific interest in the new state of quantum matter as well as the technology potential for a new generation of THz optoelectronics, ...spintronics and quantum computations. It is important to elucidate the dynamics of the Dirac fermions in the topologically protected surface state. Hence we utilized a novel ultrafast optical pump mid-infrared probe to explore the dynamics of Dirac fermions near the Dirac point. The femtosecond snapshots of the relaxation process were revealed by the ultrafast optics. Specifically, the Dirac fermion-phonon coupling strength in the Dirac cone was found to increase from 0.08 to 0.19 while Dirac fermions were away from the Dirac point into higher energy states. Further, the energy-resolved transient reflectivity spectra disclosed the energy loss rate of Dirac fermions at room temperature was about 1 meV/ps. These results are crucial to the design of Dirac fermion devices.
Background
The aim of this study was to evaluate whether adjuvant chemotherapy is associated with improved survival in patients with resectable gastric neuroendocrine carcinomas (G‐NECs) or mixed ...adenoneuroendocrine carcinomas (G‐MANECs).
Methods
The study included patients with G‐NECs or G‐MANECs who underwent surgery in one of 21 centres in China between 2004 and 2016. Propensity score matching analysis was used to reduce selection bias, and overall survival (OS) in different treatment groups was estimated by the Kaplan–Meier method.
Results
In total, 804 patients with resectable G‐NECs or G‐MANECs were included, of whom 490 (60·9 per cent) received adjuvant chemotherapy. After propensity score matching, OS in the chemotherapy group was similar to that in the no‐chemotherapy group. Among patients with G‐NECs, survival in the fluorouracil (5‐FU)‐based chemotherapy group and the non‐5‐FU‐based chemotherapy group was similar to that in the no‐chemotherapy group. Similarly, etoposide plus cisplatin or irinotecan plus cisplatin was not associated with better OS in patients with G‐NECs. Among patients with G‐MANECs, OS in the non‐5‐FU‐based chemotherapy group was worse than that in the no‐chemotherapy group. Patients with G‐MANECs did not have better OS when platinum‐based chemotherapy was
used.
Conclusion
There was no survival benefit in patients who received adjuvant chemotherapy for G‐NECs or G‐MANECs.
Antecedentes
El objetivo de este estudio fue evaluar si la quimioterapia adyuvante mejoraba la supervivencia en pacientes con carcinomas gástricos resecables neuroendocrinos (gastric neuroendocrine carcinomas, G‐NECs) y carcinomas adenoneuroendocrinos mixtos (mixed adenoneuroendocrine carcinomas, G‐MANECs).
Métodos
Se incluyeron pacientes con G‐NECs y G‐MANECs tratados quirúrgicamente en 21 centros en China entre 2004 y 2016. Se utilizó un análisis de emparejamiento por puntaje de propensión para reducir el sesgo de selección y el método de Kaplan‐Meier para estimar la supervivencia global (overall survival, OS) de los pacientes en los diferentes grupos de tratamiento.
Resultados
En total, se incluyeron en el estudio 804 pacientes con G‐NECs y G‐MANECs resecables y 490 pacientes (60,9%) recibieron quimioterapia adyuvante. Después del emparejamiento por puntaje de propensión, la OS del grupo con quimioterapia fue similar a la del grupo sin quimioterapia. En los pacientes con G‐NECs, la supervivencia en los grupos con quimioterapia basada en 5‐FU (fluorouracilo) y de quimioterapia sin 5‐FU fue similar a la del grupo sin quimioterapia. Asimismo, la combinación de etopósido y cisplatino o de irinotecán y cisplatino no se asoció con una mejor OS en pacientes con G‐NECs. En pacientes con G‐MANECs, la OS del grupo con quimioterapia sin 5‐FU fue peor que la del grupo sin quimioterapia. Los pacientes con G‐MANECs no presentaron una mejor OS cuando se administró quimioterapia basada en platinos.
Conclusión
La administración de quimioterapia adyuvante en pacientes con G‐NECs y G‐MANECs no mejoró la supervivencia.
This multicentre study enrolled 804 patients with resectable gastric neuroendocrine carcinomas and gastric mixed adenoneuroendocrine carcinomas. In propensity score matching analysis, there were no associations between the use of adjuvant chemotherapy and improved overall survival. Similar results were obtained in stratified analysis according to different chemotherapy regimens.
No benefit
Twin and family studies have shown that same-sex sexual behavior is partly genetically influenced, but previous searches for specific genes involved have been underpowered. We performed a genome-wide ...association study (GWAS) on 477,522 individuals, revealing five loci significantly associated with same-sex sexual behavior. In aggregate, all tested genetic variants accounted for 8 to 25% of variation in same-sex sexual behavior, only partially overlapped between males and females, and do not allow meaningful prediction of an individual's sexual behavior. Comparing these GWAS results with those for the proportion of same-sex to total number of sexual partners among nonheterosexuals suggests that there is no single continuum from opposite-sex to same-sex sexual behavior. Overall, our findings provide insights into the genetics underlying same-sex sexual behavior and underscore the complexity of sexuality.
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