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Given continuous development in society and the economy, obesity has become a global epidemic, arousing great concern. In addition to genetic and dietary factors, exposure to environmental chemicals is associated with the occurrence and development of obesity. Current research has indicated that some chemicals with endocrine-disrupting effects can affect lipid metabolism in vivo, causing elevated lipid storage. These chemicals are called "environmental obesogens". Synthetic phenolic compounds (SPCs) are widely used in industrial and daily products, such as plastic products, disinfectants, pesticides, food additives, and so on. The exposure routes of SPCs to the human body may include food and water consumption, direct skin contact, etc. Their unintended exposure could cause harmful effects on human health. As a type of endocrine disruptor, SPCs interfere with adipogenesis and lipid metabolism, exhibiting the characteristics of environmental obesogens. Because SPCs have similar phenolic structures, gathering information on their influences on lipid metabolism would be helpful to understand their structure-related effects. In this review, three commonly used research methods for screening environmental obesogens, including in vitro testing for molecular interactions, cell adipogenic differentiation models, and in vivo studies on lipid metabolism, are summarized, and the advantages and disadvantages of these methods are compared and discussed. Based on both in vitro and in vivo data, three types of SPCs, including bisphenol A (BPA) and its analogues, alkylphenols (APs), and synthetic phenolic antioxidants (SPAs), are systematically discussed in terms of their ability to disrupt adipogenesis and lipid metabolism by focusing on adipose and hepatic tissues, among others. Common findings on the effects of these SPCs on adipocyte differentiation, lipid storage, hepatic lipid accumulation, and liver steatosis are described. The underlying toxicological mechanisms are also discussed from the aspects of nuclear receptor transactivation, inflammation and oxidative stress regulation, intestinal microenvironment alteration, epigenetic modification, and some other signaling pathways. Future research to increase public knowledge on the obesogenic effects of emerging chemicals of concern is encouraged.
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Disruptores Endócrinos , Metabolismo dos Lipídeos , Humanos , Exposição Ambiental , Obesidade/etiologia , Obesidade/genética , Adipogenia , Disruptores Endócrinos/farmacologia , Compostos Benzidrílicos , LipídeosRESUMO
Extracellular aggregation of amyloid-beta (Aß) and intracellular tau tangles are two major pathogenic hallmarks and critical factors of Alzheimer's disease. A linear interaction between Aß and tau protein has been characterized in several models. Aß induces tau hyperphosphorylation through a complex mechanism; however, the master regulators involved in this linear process are still unclear. In our study with Drosophila melanogaster, we found that Aß regulated tau hyperphosphorylation and toxicity by activating c-Jun N-terminal kinase. Importantly, Aß toxicity was dependent on tau hyperphosphorylation, and flies with hypophosphorylated tau were insulated against Aß-induced toxicity. Strikingly, tau accumulation reciprocally interfered with Aß degradation and correlated with the reduction in mRNA expression of genes encoding Aß-degrading enzymes, including dNep1, dNep3, dMmp2, dNep4, and dIDE. Our results indicate that Aß and tau protein work synergistically to further accelerate Alzheimer's disease progression and may be considered as a combined target for future development of Alzheimer's disease therapeutics.
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A novel nanosecond transient electric field (E-field) measurement system is developed in this paper to measure the E-field pulse caused by the operation of the high-voltage switch (switching E-field pulse) in the substation. An electrically small rod antenna is used as the receiving antenna and is matched by the operational amplifier with high input impedance to achieve broadband frequency response and stable working performance. A broadband analog optical fiber transmission system is further designed based on the high-frequency circuit model of the electronic components. Unlike the traditional frequency domain E-field measurement methods, the developed measurement system can directly output the time domain waveform of the switching E-field pulse. It also has the advantages of adjustable sensitivity, portability, and anti-electromagnetic interference. The calibrated measurement bandwidth ranges from 200 Hz to 680 MHz. Furthermore, the switching E-field pulse in an ultra-high voltage substation is measured and analyzed to verify the effectiveness of the fabricated measurement system.
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Exploring stable clusters to understand structural evolution from atoms to macroscopic matter and to construct new materials is interesting yet challenging in chemistry. Utilizing our newly developed deep-ultraviolet laser ionization mass spectrometry technique, here we observe the reactions of neutral cobalt clusters with oxygen and find a very stable cluster species of Co13O8 that dominates the mass distribution in the presence of a large flow rate of oxygen gas. The results of global-minimum structural search reveal a unique cubic structure and distinctive stability of the neutral Co13O8 cluster that forms a new class of metal oxides that we named as 'metalloxocubes'. Thermodynamics and kinetics calculations illustrate the structural evolution from icosahedral Co13 to the metalloxocube Co13O8 with decreased energy, enhanced stability and aromaticity. This class of neutral oxygen-passivated metal clusters may be an ideal candidate for genetic materials because of the cubic nature of the building blocks and the stability due to cubic aromaticity.
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We report a joint experimental and theoretical study on the reactions of cobalt clusters (Con±/0) with nitrogen using the customized reflection time-of-flight mass spectrometer combined with a 177.3 nm deep-ultraviolet laser. Comparing to the behaviors of neutral Con (n = 2-30) and anionic Con- clusters (n = 7-53) which are relatively inert in reacting with nitrogen in the fast-flow tube, Con+ clusters readily react with nitrogen resulting in adducts of one or multiple N2 except Co6+ which stands firm in the reaction with nitrogen. Detailed quantum chemistry calculations, including the energetics, electron occupancy, and orbital analysis, well-explained the reasonable reactivity of Con+ clusters with nitrogen and unveiled the open-shell superatomic stability of Co6+ within a highly symmetric (D3d) structure. The D3d Co6+ bears an electron configuration of a half-filled superatomic 1P orbital (i.e., 1S21P3||1D0), a large α-highest occupied molecular orbital (HOMO)-lowest unoccupied molecular orbital (LUMO) gap, symmetric multicenter bonds, and reasonable electron delocalization pertaining to metallic aromaticity. Topology analysis by atom-in-molecule illustrates the interactions between Con+ and N2 corresponding to covalent bonds, but the Co-N interactions in cationic Co2+N2 and Co6+N2 clusters are apparently weaker than those in the other systems. In addition, we identify a superatomic complex Co5N6+ which exhibits similar frontier orbitals as the naked Co5+ cluster, but the alpha HOMO-LUMO gap is nearly double-magnified, which is consistent with the high-abundance peak of Co5N6+ in the experimental observation. The enhanced stability of such a ligand-coordinated superatomic complex Co5N6+, along with the superatom Co6+ with aromaticity, sheds light on special and general superatoms.
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A customized reflection time-of-flight (Re-TOF) mass spectrometer combined with a 177 nm deep-ultraviolet laser has enabled us to observe well-resolved cobalt clusters Con±/0 and perform a comprehensive study of their reactivity with ammonia (NH3). The anions Con- are found to be inert, the neutrals allow the adsorption of multiple NH3 molecules, while the cationic Con+ clusters readily react with NH3 giving rise to dehydrogenation. However, incidental dehydrogenation of NH3 on Con+ is only observed for n ≥ 3. The dramatic charge- and size-dependent reactivities of Con±/0 clusters with NH3 are studied by the density functional theory (DFT)-calculation results of energetics, density of states, orbital interactions, and reaction dynamics. We illustrate the dehydrogenation from two NH3 molecules, where a significantly reduced transition-state energy barrier is found pertaining to the dimolecular co-catalysis effect. The reactivity of Co3+ with NH3 is illustrated showing effective catalysis for N-H dissociation to produce hydrogen applicable for designing ammonia fuel cells.
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Lamb-dip spectroscopy of the C-N stretching band of methylamine has been systematically extended to P-, Q-, and R-branch by using microwave sidebands of a large number of CO2 laser lines as frequency-tunable infrared sources in a sub-Doppler spectrometer. Lamb-dip signals of more than 150 spectral lines have been observed with a resolution of 0.4 MHz and their frequencies have been precisely measured with an accuracy of ±0.1 MHz. More than 30 closed combination loops have been formed, which unambiguously confirm the assignments. For over 150 vibrational excited levels in 27 substates, refined term values have been determined and expanded in J(J + 1) power-series to determine the substate origins and the effective rotational constants. For transitions with Aa torsion-inversion symmetry in torsional state υt = 0, 57 K-doublet lines displaying asymmetry splittings have been observed and the splitting constants for levels with K = 1, 2, and 3 in the excited states have been determined. Our results provide accurate experimental information for spectroscopic studies of the interesting vibrational perturbations and intermode interactions related to the C-N stretching mode, directly support astronomical surveys, and are very relevant in practice to identification and frequency determination of the CO2-laser-pumped far-infrared laser lines of methylamine.
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All symmetrical molecules with non-zero nuclear spin exist in nature as nuclear-spin isomers (NSIs). However, owing to the lack of experimental information, knowledge is rare about interconversions of NSIs of gaseous molecules with torsional symmetry. Here we report our separation and conversion observations on NSI-torsion-specific transition systems of gaseous methanol from a light-induced drift experiment involving partially spatial separation of the ortho and para isomers. We find that vibrationally excited molecules of the methanol spin isomer have a smaller collision cross-section than their ground-state counterparts. Interconversion of the enriched ortho isomer with the para isomer, which is generally considered improbable, has been quantitatively studied by sensitive detections of the spectral intensities. Rather counterintuitively, this reveals that the interconversion is inhibited with increasing pressure. Our results suggest that the spin conversion mechanism in methanol is via a quantum relaxation process with the quantum Zeno effect induced by molecular collisions.
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Heat shock protein 70 (HSP70) protects cardiac function against ischemia-reperfusion injury through gene transfection, although it is not a clinically practical and economical method. This study investigated whether heat stress-induced HSP70 protects heterotopically transplanted donor hearts. A total of 60 donor rats were randomly divided into 6 groups. Five of those received heat stress and one was a control group. Donor hearts were heterotopically transplanted into recipient rats at five time points, following the heat stress (0, 24, 48, 96 and 192 h). The levels of HSP70 expression in donor hearts and the variation of myocardial enzymes in receptor blood or donor hearts were measured 24 h after transplantation. The donated hearts were also examined under a microscope for pathological changes. HSP70 expression was the highest in the 24-h group (p≤0.01) and decreased gradually in the 48- and 96-h groups. No statistically significant difference was found in the HSP70 expression in the control, the 0- and 192-h groups (p≥0.05). Of all the groups, the 24-h group had the lowest lactate dehydrogenase and creatine kinase muscle band concentrations in receptor blood. Moreover, this group showed the lowest malondialdehyde concentration and the highest atriphosphate concentration (p≤0.01), demonstrated by the mildest inflammatory injury in the transplanted hearts. We found a time-dose-effect relationship among heat stress, HSP70 and the protection of donor hearts. Heat stress is a practical method that can be clinically applied to protect donor hearts against ischemia-reperfusion injury by inducing endogenous HSP70, which indicates the future direction of clinical practice.
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Proteínas de Choque Térmico HSP70/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Creatina Quinase/metabolismo , Transplante de Coração , L-Lactato Desidrogenase/metabolismo , Masculino , Malondialdeído/metabolismo , Miocárdio/metabolismo , Miocárdio/patologia , Ratos , Ratos Wistar , Temperatura , Fatores de Tempo , Transplante HeterotópicoRESUMO
The C-N stretching infrared fundamental of CH(3)NH(2) has been investigated by high-resolution laser sideband and Fourier transform synchrotron spectroscopy to explore the energy level structure and to look for possible interactions with high-lying torsional levels of the ground state and other vibrational modes. The spectrum is complicated by two coupled large-amplitude motions in the molecule, the CH(3) torsion and the NH(2) inversion, which lead to rich spectral structure with a wide range of energy level splittings and relative line intensities. Numerous sub-bands have been assigned for K values ranging up to 12 for the stronger a inversion species for the v(t) = 0 torsional state, along with many of the weaker sub-bands of the s species. The C-N stretching sub-state origins have been determined by fitting the upper-state term values to J(J + 1) power-series expansions. For comparison with the ground-state behaviour, both ground and C-N stretch origins have been fitted to a phenomenological Fourier series model that produces an interesting pattern with the differing periodicities of the torsional and inversion energies. The amplitude of the torsional energy oscillation increases substantially for the C-N stretch, while the amplitude of the inversion energy oscillation is relatively unchanged. Independent inertial scale factors ρ were fitted for the torsion and the inversion and differ significantly in the upper state. The C-N stretching vibrational energy is determined to be 1044.817 cm(-1), while the effective upper state B-value is 0.7318 cm(-1). Several anharmonic resonances with v(t) = 4 ground-state levels have been observed and partially characterized. A variety of J-localized level-crossing resonances have also been seen, five of which display forbidden transitions arising from intensity borrowing that allow determination of the interaction coupling constants.
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Metilaminas/química , Dióxido de Carbono/química , Lasers , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
We report saturation dip spectroscopy in the C-N stretching band of CH(3)NH(2) with a resolution of 0.4 MHz and an accuracy of 0.1 MHz by use of a CO(2)-laser/microwave-sideband spectrometer. The wide tunability, Lamb-dip resolution, absolute frequency accuracy, and high sensitivity of our dual-mode instrument were all key features in making precise measurements for a range of lines in the densely crowded spectrum with its complex pattern of splittings arising from the large-amplitude CH(3) torsion and NH(2) inversion. We focused on achieving resolution and assignment of transitions within the highly blended Q branch of the C-N stretch and on observations of the important K=0 sequences of Aa and Ea torsion-inversion symmetry. Term values of the latter were fitted to J(J+1) power-series expansions to obtain the K=0 C-N stretching effective B values and substate origins, from which calculated ground-state substate energies were subtracted to yield values of 1044.7061 and 1044.8011 cm(-1) for the Aa and Ea subband origins, respectively. We thereby estimate a mean value of 1044.75(5) cm(-1) for the vibrational band origin and 0.7323(5) cm(-1) for the effective upper-state B value for the C-N stretching fundamental of CH(3)NH(2).
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Dióxido de Carbono/química , Lasers , Metilaminas/química , Micro-Ondas , Espectrofotometria InfravermelhoRESUMO
Molecules with three or more nuclei of nonzero spin exist as discrete spin isomers whose interconversion in the gas phase is generally considered improbable. We have studied the interconversion process in ethylene by creating a sample depleted in the B2u nuclear spin isomer. The separation was achieved through spatial drift of this isomer induced by resonant absorption of narrow-band infrared light. Evolution of the depleted sample revealed conversion between B2u and B3u isomers at a rate linearly proportional to pressure, with a rate constant of 5.5 (+/-0.8) x 10(-4) s(-1) torr(-1). However, almost no change was observed in the Ag isomer populations. The results suggest a spin conversion mechanism in C2H4 via quantum relaxation within the same inversion symmetry.