Quasi-Periodic Variations in X-ray Emission and Long-Term Radio Observations: Evidence for a Two-Component Jet in Sw J1644+57

The continued observations of Sw J1644+57 in X-ray and radio bands accumulated a rich data set to study the relativistic jet launched in this tidal disruption event. The X-ray light curve of Sw J1644+57 from 5-30 days presents two kinds of quasi-periodic variations: a 200 second quasi-periodic oscillation (QPO) and a 2.7-day quasi-periodic variation. The latter has been interpreted by a precessing jet launched near the Bardeen-Petterson radius of a warped disk. Here we suggest that the $\sim$ 200s QPO could be associated with a second, narrower jet sweeping the observer line-of-sight periodically, which is launched from a spinning black hole in the misaligned direction with respect to the black hole's angular momentum. In addition, we show that this two-component jet model can interpret the radio light curve of the event, especially the re-brightening feature starting $\sim 100$ days after the trigger. From the data we infer that inner jet may have a Lorentz factor of $\Gamma_{\rm j} \sim 5.5$ and a kinetic energy of $E_{\rm k,iso} \sim 3.0 \times 10^{52} {\rm erg}$, while the outer jet may have a Lorentz factor of $\Gamma_{\rm j} \sim 2.5$ and a kinetic energy of $E_{\rm k,iso} \sim 3.0 \times 10^{53} {\rm erg}$.Comment: 11 pages, 7 figures, accepted for publication in Ap

Transcriptome Analysis of Small Molecule–Mediated Astrocyte-to-Neuron Reprogramming

Chemical reprogramming of astrocytes into neurons represents a promising approach to regenerate new neurons for brain repair, but the underlying mechanisms driving this trans-differentiation process are not well understood. We have recently identified four small molecules – CHIR99021, DAPT, LDN193189, and SB431542 – that can efficiently reprogram cultured human fetal astrocytes into functional neurons. Here we employ the next generation of RNA-sequencing technology to investigate the transcriptome changes during the astrocyte-to-neuron (AtN) conversion process. We found that the four small molecules can rapidly activate the hedgehog signaling pathway while downregulating many glial genes such as FN1 and MYL9 within 24 h of treatment. Chemical reprogramming is mediated by several waves of differential gene expression, including upregulation of hedgehog, Wnt/β-catenin, and Notch signaling pathways, together with downregulation of TGF-β and JAK/STAT signaling pathways. Our gene network analyses reveal many well-connected hub genes such as repulsive guidance molecule A (RGMA), neuronatin (NNAT), neurogenin 2 (NEUROG2), NPTX2, MOXD1, JAG1, and GAP43, which may coordinate the chemical reprogramming process. Together, these findings provide critical insights into the molecular cascades triggered by a combination of small molecules that eventually leads to chemical conversion of astrocytes into neurons

The potential impact of primary headache disorders on stroke risk

Distribution of PHDs. (DOC 55 kb

The optimal pulse pressures for healthy adults with different ages and sexes correlate with cardiovascular health metrics

BackgroundPulse pressure (PP) may play a role in the development of cardiovascular disease, and the optimal PP for different ages and sexes is unknown. In a prospective cohort, we studied subjects with favorable cardiovascular health (CVH), proposed the mean PP as the optimal PP values, and demonstrated its relationship with healthy lifestyles.Methods and resultsBetween 1996 and 2016, a total of 162,636 participants (aged 20 years or above; mean age 34.9 years; 26.4% male subjects; meeting criteria for favorable health) were recruited for a medical examination program. PP in male subjects was 45.6 ± 9.4 mmHg and increased after the age of 50 years. PP in female subjects was 41.8 ± 9.5 mmHg and increased after the age of 40 years, exceeding that of male subjects after the age of 50 years. Except for female subjects with a PP of 40–70 mmHg, PP increase correlates with both systolic blood pressure (BP) increase and diastolic BP decrease. Individuals with mean PP values are more likely to meet health metrics, including body mass index (BMI) <25 kg/m2 (chi-squared = 9.35, p<0.01 in male subjects; chi-squared = 208.79, p < 0.001 in female subjects) and BP <120/80 mmHg (chi-squared =1,300, p < 0.001 in male subjects; chi-squared =11,000, p < 0.001 in female subjects). We propose a health score (Hscore) based on the sum of five metrics (BP, BMI, being physically active, non-smoking, and healthy diet), which significantly correlates with the optimal PP.ConclusionThe mean PP (within ±1 standard deviation) could be proposed as the optimal PP in the adult population with favorable CVH. The relationship between health metrics and the optimal PP based on age and sex was further demonstrated to validate the Hscore

Integrated chemical characterization, metabolite profiling, and pharmacokinetics analysis of Zhijun Tangshen Decoction by UPLC-Q/TOF-MS

Diabetic nephropathy (DN) is the main cause of end-stage renal disease worldwide and a major public issue affecting the health of people. Therefore, it is essential to explore effective drugs for the treatment of DN. In this study, the traditional Chinese medicine (TCM) formula, Zhijun Tangshen Decoction (ZJTSD), a prescription modified from the classical formula Didang Decoction, has been used in the clinical treatment of DN. However, the chemical basis underlying the therapeutic effects of ZJTSD in treating DN remains unknown. In this study, compounds of ZJTSD and serum after oral administration in rats were identified and analyzed using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS). Meanwhile, a semi-quantitative approach was used to analyze the dynamic changes in the compounds of ZJTSD in vivo. UPLC-Q/TOF-MS analysis identified 190 compounds from ZJTSD, including flavonoids, anthraquinones, terpenoids, phenylpropanoids, alkaloids, and other categories. A total of 156 xenobiotics and metabolites, i.e., 51 prototype compounds and 105 metabolites, were identified from the compounds absorbed into the blood of rats treated with ZJTSD. The results further showed that 23 substances with high relative content, long retention time, and favorable pharmacokinetic characteristics in vivo deserved further investigations and validations of bioactivities. In conclusion, this study revealed the chemical basis underlying the complexity of ZJTSD and investigated the metabolite profiling and pharmacokinetics of ZJTSD-related xenobiotics in rats, thus providing a foundation for further investigation into the pharmacodynamic substance basis and metabolic regulations of ZJTSD

Core and penumbra estimation using deep learning-based AIF in association with clinical measures in computed tomography perfusion (CTP)

Objectives To investigate whether utilizing a convolutional neural network (CNN)-based arterial input function (AIF) improves the volumetric estimation of core and penumbra in association with clinical measures in stroke patients. Methods The study included 160 acute ischemic stroke patients (male = 87, female = 73, median age = 73 years) with approval from the institutional review board. The patients had undergone CTP imaging, NIHSS and ASPECTS grading. convolutional neural network (CNN) model was trained to fit a raw AIF curve to a gamma variate function. CNN AIF was utilized to estimate the core and penumbra volumes which were further validated with clinical scores. Results Penumbra estimated by CNN AIF correlated positively with the NIHSS score (r = 0.69; p  20) and lower ASPECT score ( 10 s, Tmax > 10 s volumes were statistically significantly higher (p < .05). Conclusions With inclusion of the CNN AIF in perfusion imaging pipeline, penumbra and core estimations are more reliable as they correlate with scores representing neurological deficits in stroke. Critical relevance statement With CNN AIF perfusion imaging pipeline, penumbra and core estimations are more reliable as they correlate with scores representing neurological deficits in stroke