Highlights • Gastrodin improves learning and memory abilities of Tg2576 mice. • Gastrodin attenuates intracellular oxidative stress in hippocampi of Tg2576 mice. • Gastrodin suppresses BACE1 ...expression and PKR/eIF2α pathway in hippocampi of Tg2576 mice. • Gastrodin suppresses BACE1 via inhibiting PKR/eIF2α in SH-SY5Y cells under oxidative stress.
Osteoarthritis is a common disease that can cause severe pain and dysfunction in any joint, including the temporomandibular joint (TMJ). TMJ osteoarthritis (TMJOA) is an important subtype in the ...classification of temporomandibular disorders. TMJOA pathology is characterized by progressive cartilage degradation, subchondral bone remodeling, and chronic inflammation in the synovial tissue. However, the exact pathogenesis and process of TMJOA remain to be understood. An increasing number of studies have recently focused on inflammation and remodeling of subchondral bone during the early stage of TMJOA, which may elucidate the possible mechanism of initiation and progression of TMJOA. The treatment strategy for TMJOA aims at relieving pain, preventing the progression of cartilage and subchondral bone destruction, and restoring joint function. Conservative therapy with nonsteroidal anti-inflammatory drugs, splint, and physical therapy, such as low-energy laser and arthrocentesis, are the most common treatments for TMJOA. These therapies are effective in most cases in relieving the signs and symptoms, but their long-term therapeutic effect on the pathologic articular structure is unsatisfactory. A treatment that can reverse the damage of TMJOA remains unavailable to date. Treatments that prevent the progression of cartilage degradation and subchondral bone damage should be explored, and regeneration for the TMJ may provide the ideal long-term solution. This review summarizes the current understanding of mechanisms underlying the pathogenesis and treatment of TMJOA.
The paper presented a working fluid selection and parametric optimization using a multi-objective optimization model by simulated annealing algorithm. The screening criteria considered included heat ...exchanger area per unit power output (A/Wnet) and heat recovery efficiency (Ф). The independent parameters are the evaporation and condensation pressures, working fluid and cooling water velocities in tubes. A comparison of optimized results for 13 working fluids shows that boiling temperature of working fluids will greatly affect the optimal evaporating pressure. R123 is the best choice for the temperature range of 100–180°C and R141b is the optimal working fluid when the temperature higher than 180°C. When the exhaust temperature ranges from 100°C to 220°C, the optimal pinch point at evaporator is about 15°C. Economic characteristic of system decreases rapidly with heat source temperature decrease. When the heat source temperature is lower than 100°C, ORC technology is uneconomical.
► The optimal working fluid is selected for different heat source temperature. ► The boiling temperature of working fluids can greatly affect the optimal evaporating pressure. ► The optimal pinch point at evaporator is about 15 C ► The ORC technology is unsuitable for the waste heat that the temperature is lower than 100 C.
Emerging evidences suggest that necrosis is programmed and is one of the main forms of cell death in the pathological process in cardiac diseases. Long noncoding RNAs (lncRNAs) are emerging as new ...players in gene regulation. However, it is not yet clear whether lncRNAs can regulate necrosis in cardiomyocytes. Here, we report that a long noncoding RNA, named necrosis-related factor (NRF), regulates cardiomyocytes necrosis by targeting miR-873 and RIPK1 (receptor-interacting serine/threonine-protein kinase 1)/RIPK3 (receptor-interacting serine/threonine-protein kinase 3). Our results show that RIPK1 and RIPK3 participate in H2O2-induced cardiomyocytes necrosis. miR-873 suppresses the translation of RIPK1/RIPK3 and inhibits RIPK1/RIPK3-mediated necrotic cell death in cardiomyocytes. miR-873 reduces myocardial infarct size upon ischemia/reperfusion (I/R) injury in the animal model. In exploring the molecular mechanism by which miR-873 expression is regulated, we identify NRF as an endogenous sponge RNA and repress miR-873 expression. NRF directly binds to miR-873 and regulates RIPK1/RIPK3 expression and necrosis. Knockdown of NRF antagonizes necrosis in cardiomyocytes and reduces necrosis and myocardial infarction upon I/R injury. Further, we identify that p53 transcriptionally activates NRF expression. P53 regulates cardiomyocytes necrosis and myocardial I/R injury through NRF and miR-873.Our results identify a novel mechanism involving NRF and miR-873 in regulating programmed necrosis in the heart and suggest a potential therapeutic avenue for cardiovascular diseases.
Hyperactivity of corticotropin-releasing factor (CRF) neurons in the paraventricular nucleus (PVN) of the hypothalamus is a prominent feature in depression and may be important in the etiology of ...this disease. The activity of the CRF neurons in the stress response is modulated by a number of factors that stimulate or inhibit CRF expression, including (1) corticosteroid receptors and their chaperones, heat shock proteins 70 and 90, (2) sex hormone receptors, (3) CRF receptors 1 (CRFR1) and 2, (4) cytokines interleukin 1-beta and tumor necrosis factor-alpha, (5) neuropeptides and receptors, vasopressin (AVP), AVP receptor 1a (AVPR1A) and oxytocin and (6) transcription factor cAMP-response element-binding protein. We hypothesized that, in depression, the transcript levels of those genes that are involved in the activation of the hypothalamo-pituitary-adrenal (HPA) axis are upregulated, whereas the transcript levels of the genes involved in the inhibition of the HPA axis are downregulated. We performed laser microdissection and real-time PCR in the PVN and as a control in the supraoptic nucleus. Snap-frozen post-mortem hypothalami of seven depressed and seven matched controls were used. We found significantly increased CRF mRNA levels in the PVN of the depressed patients. This was accompanied by a significantly increased expression of four genes that are involved in the activation of CRF neurons, that is, CRFR1, estrogen receptor-alpha, AVPR1A and mineralocorticoid receptor, while the expression of the androgen receptor mRNA involved in the inhibition of CRF neurons was decreased significantly. These findings raise the possibility that a disturbed balance in the production of receptors may contribute to the activation of the HPA axis in depression.
Two pairs of positive-and negative-parity doublet bands together with eight strong electric dipole transitions linking their yrast positive- and negative-parity bands have been identified in ^{78}Br. ...They are interpreted as multiple chiral doublet bands with octupole correlations, which is supported by the microscopic multidimensionally-constrained covariant density functional theory and triaxial particle rotor model calculations. This observation reports the first example of chiral geometry in octupole soft nuclei.
Alcohol's impact on telomere length, a proposed marker of biological aging, is unclear. We performed the largest observational study to date (in n = 245,354 UK Biobank participants) and compared ...findings with Mendelian randomization (MR) estimates. Two-sample MR used data from 472,174 participants in a recent genome-wide association study (GWAS) of telomere length. Genetic variants were selected on the basis of associations with alcohol consumption (n = 941,280) and alcohol use disorder (AUD) (n = 57,564 cases). Non-linear MR employed UK Biobank individual data. MR analyses suggested a causal relationship between alcohol traits, more strongly for AUD, and telomere length. Higher genetically-predicted AUD (inverse variance-weighted (IVW) β = -0.06, 95% confidence interval (CI): -0.10 to -0.02, p = 0.001) was associated with shorter telomere length. There was a weaker association with genetically-predicted alcoholic drinks weekly (IVW β = -0.07, CI: -0.14 to -0.01, p = 0.03). Results were consistent across methods and independent from smoking. Non-linear analyses indicated a potential threshold relationship between alcohol and telomere length. Our findings indicate that alcohol consumption may shorten telomere length. There are implications for age-related diseases.
Because of the development of many-body theories of nuclear matter, the long-standing, open problem of the equation of state (EOS) of dense matter may be understood in the near future through the ...confrontation of theoretical calculations with laboratory measurements of nuclear properties & reactions and increasingly accurate observations in astronomy. In this review, we focus on the following six aspects: 1) providing a survey of the quark mean-field (QMF) model, which consistently describes a nucleon and many-body nucleonic system from a quark potential; 2) applying QMF to both nuclear matter and neutron stars; 3) extending QMF formalism to the description of hypernuclei and hyperon matter, as well as hyperon stars; 4) exploring the hadron-quark phase transition and hybrid stars by combining the QMF model with the quark matter model characterized by the sound speed; 5) constraining interquark interactions through both the gravitational wave signals and electromagnetic signals of binary merger event GW170817; and 6) discussing further opportunities to study dense matter EOS from compact objects, such as neutron star cooling and pulsar glitches.
DS Tuc Ab is a Neptune-sized planet that orbits around a G star in the 45 Myr old Tucana-Horologium moving group. Here, we report the measurement of the sky-projected angle between the stellar spin ...axis and the planet's orbital axis, based on the observation of the Rossiter-McLaughlin effect during three separate planetary transits. The orbit appears to be well aligned with the equator of the host star, with a projected obliquity of . In addition to the distortions in the stellar absorption lines due to the transiting planet, we observed variations that we attribute to large starspots, with angular sizes of tens of degrees. The technique that we have developed for simultaneous modeling of starspots and the planet-induced distortions may be useful in other observations of planets around active stars.
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