Neonatal hyperbilirubinemia is a common clinical condition that can lead to brain encephalopathy, particularly when concurrent with acidosis due to infection, ischemia, and hypoxia. The prevailing ...view is that acidosis increases the permeability of the blood-brain barrier to bilirubin and exacerbates its neurotoxicity. In this study, we found that the concentration of the cell death marker, lactate dehydrogenase (LDH) in cerebrospinal fluid (CSF), is elevated in infants with both hyperbilirubinemia and acidosis and showed stronger correlation with the severity of acidosis rather than increased bilirubin concentration. In mouse neonatal neurons, bilirubin exhibits limited toxicity but robustly potentiates the activity of acid-sensing ion channels (ASICs), resulting in increases in intracellular Ca
concentration, spike firings, and cell death. Furthermore, neonatal conditioning with concurrent hyperbilirubinemia and hypoxia-induced acidosis promoted long-term impairments in learning and memory and complex sensorimotor functions in vivo, which are largely attenuated in ASIC1a null mice. These findings suggest that targeting acidosis and ASICs may attenuate neonatal hyperbilirubinemia complications.
Highlights • miR-379-5p is significantly down-regulated in HCC. • miR-379-5p can inhibit HCC invasion and metastasis. • FAK is a direct target of miR-379-5p. • miR-379-5p exerts its functions through ...inhibiting FAK/AKT signaling. • miR-379-5p might be a potential therapeutic target and prognostic marker for HCC.
Aerodynamic pressures and forces on a two-dimensional square cylinder were experimentally investigated in large-scale sinusoidal gusts. The effects of streamwise and transverse gusts with a wide ...range of gust amplitudes were studied at a Reynolds number of Re = 2.1 × 104. To enhance our understanding of the large-scale sinusoidal gust effect, the pressure fields and global aerodynamic forces of the square cylinder in large-scale gusts were compared with those in smooth and grid-generated turbulent flows. This study shows that both large-scale streamwise and transverse gusts can promote early pressure recovery, resulting in larger mean pressures on the side and leeward surfaces. The root mean square (RMS) of the pressures on the side surface increased and decreased with an increase in the streamwise and transverse gust amplitudes, respectively. The mean drag on the square cylinder was reduced under the effects of large-scale streamwise and transverse gusts. The increase in the streamwise and transverse gust amplitudes significantly affected the RMS of the drag and lift on the square cylinder, respectively. A proper orthogonal decomposition (POD) analysis showed that the contribution of the first POD mode switched from fluctuating lift to drag when the streamwise gust amplitude was very high. The spectral analysis demonstrated that the alternating von Kármán vortex-shedding process still dominated the fluctuating lift under the effect of large-scale gusts. In addition, the spanwise correlations of drag were significantly strong under the effects of large-scale streamwise gusts. However, the spanwise correlations of lift were reduced under the effects of large-scale gusts with high gust amplitudes.
•Actinidia chinensis Planch(ACP) suppresses proliferation and migration of gastric cancer cells.•ACP treatment elevated the apoptosis and ferroptosis but suppressed mesenchymal phenotype in HGC-27 ...cells.•ACP suppressed tumor growth in the zebrafish xenograft model.
Actinidia chinensis Planch (ACP) was the kiwifruit plant Chinese kiwifruit Actinidia chinensis Planch Root, which had been approved to be an anti-tumor drug widespread in clinical. However, the specific mechanism of ACP in resistance to gastric cancer remained unclear. Therefore, our study was dedicated to investigate the anti-proliferation and anti-migration effects of ACP on gastric cancer cells and its molecular mechanisms. Firstly, we utilized HPLC-MS to analyze the composition of ACP decoction, the results showed that ACP contained two main anti-tumor components, Ursolic acid and Oleanolic acid. The proliferation and migration ability of HGC-27 were examined by CCK-8 and cell scratch tests respectively. In addition, we also investigated HGC-27 cells apoptosis, mesenchymal phenotype and ferroptosis after ACP rat drug-containing serum (ACPs) treatment. EGFP-expressing lentiviral vectors were utilized to construct HGC-27 cells which containing green fluorescence. Then we take advantages of containing green fluorescence cells to establish a zebrafish xenograft model in vivo. The CCK-8 and cell scratch experiments verified that ACPs significantly inhibited proliferation and migration of HGC-27 in vitro. ACPs increased cells apoptosis rate, while were rescued by apoptosis inhibitor Z-VAD-FMK. Furthermore, ACPs downregulated the expression levels of Vimentin protein and Snail protein markedly. Intriguingly, ACPs increased the accumulation of ROS via inhibited the glutathione peroxidase 4 (GPx4) and xCT (SLC7A11) proteins, while were inhibited by Ferrostatin-1 (Fer-1) significantly. Furthermore, the zebrafish xenograft study further confirmed that administration of ACP suppressed the xenograft growth and metastasis of transplanted HGC-27 cells in vivo. In conclusion, ACP was a promising antineoplastic agent for the treatment of gastric cancer by regulating apoptosis, ferroptosis and mesenchymal phenotype.
Hydrogen produced from neutral seawater electrolysis faces many challenges including high energy consumption, the corrosion/side reactions caused by Cl
, and the blockage of active sites by Ca
/Mg
...precipitates. Herein, we design a pH-asymmetric electrolyzer with a Na
exchange membrane for direct seawater electrolysis, which can simultaneously prevent Cl
corrosion and Ca
/Mg
precipitation and harvest the chemical potentials between the different electrolytes to reduce the required voltage. In-situ Raman spectroscopy and density functional theory calculations reveal that water dissociation can be promoted with a catalyst based on atomically dispersed Pt anchored to Ni-Fe-P nanowires with a reduced energy barrier (by 0.26 eV), thus accelerating the hydrogen evolution kinetics in seawater. Consequently, the asymmetric electrolyzer exhibits current densities of 10 mA cm
and 100 mA cm
at voltages of 1.31 V and 1.46 V, respectively. It can also reach 400 mA cm
at a low voltage of 1.66 V at 80 °C, corresponding to the electricity cost of US$1.36 per kg of H
($0.031/kW h for the electricity bill), lower than the United States Department of Energy 2025 target (US$1.4 per kg of H
).
The optimal time point for surgical resection of synchronous colorectal liver metastases (SCLMs) is still controversial. This meta-analysis evaluated the safety and long-term prognoses of ...simultaneous and staged resection of SCLM to provide a reference for clinical selection.
A systematic literature search for studies published by October 2022 was performed using PubMed, Web of Science, Embase, Scopus and Cochrane Library. The evaluated outcome parameters were total, gastrointestinal and hepatic complications, as well as perioperative mortality, intraoperative blood loss, total hospital stay, 5-year disease-free survival (DFS) and 5-year overall survival (OS).
This meta-analysis included 22 nonrandomised and one randomised study comprising 4862 patients. The patients undergoing simultaneous resection of SCLM had similar total (OR = 0.88, 95% CI 0.66-1.19, P = 0.409), gastrointestinal (OR = 1.19, 95% CI 0.89-1.59, P = 0.241) and hepatic (OR = 1.04, 95% CI 0.83-1.31, P = 0.734) complications, as well as perioperative mortality (OR = 1.79, 95% CI 0.88-3.64, P = 0.108), 5-year DFS (HR = 1.26, 95% CI 0.96-1.66, P = 0.098) and 5-year OS (HR = 1.13, 95% CI 0.95-1.34, P = 0.164). Lower intraoperative blood loss (SMD = - 0.39, 95% CI - 0.60 to - 0.18, P < 0.001) and shorter total hospital stay (WMD = - 5.43, 95% CI - 7.29 to - 3.58, P < 0.001) were observed in the simultaneous-resection group versus the staged group.
Simultaneous resection is safe and effective for SCLM patients. The long-term prognosis is equivalent to that of the traditional staged resection. Correct selection of resectable SCLM patients for the simultaneous resection of the primary tumour and liver metastases can be the first choice. Owing to the potential heterogeneity, more RCTs should be included to verify our conclusions.
Gibbosterol A (1), a water-soluble 14-membered carbocyclic steroid with a twisted trans-9,11-epoxy ring, was discovered from the South China Sea dinoflagellate, Amphidinium gibbosum, together with ...its acid-induced cyclization product 2. It exhibits marked agonistic effects against human pregnane-X-receptor in a dose-dependent manner within the concentration range of 100 nM to 10 μM. Its 5/14-carbobicyclic nucleus is proposed to be originated from late-stage oxidative cleavage of the C5–C10 and C8–C9 bonds of β-sitosterol.
Abstract
The quantum Hall effect, fundamental in modern condensed matter physics, continuously inspires new theories and predicts emergent phases of matter. Here we experimentally demonstrate three ...types of Chern insulators with synthetic dimensions on a programable 30-qubit-ladder superconducting processor. We directly measure the band structures of the 2D Chern insulator along synthetic dimensions with various configurations of Aubry-André-Harper chains and observe dynamical localisation of edge excitations. With these two signatures of topology, our experiments implement the bulk-edge correspondence in the synthetic 2D Chern insulator. Moreover, we simulate two different bilayer Chern insulators on the ladder-type superconducting processor. With the same and opposite periodically modulated on-site potentials for two coupled chains, we simulate topologically nontrivial edge states with zero Hall conductivity and a Chern insulator with higher Chern numbers, respectively. Our work shows the potential of using superconducting qubits for investigating different intriguing topological phases of quantum matter.
We demonstrate the collapse and revival features of the entanglement dynamics of different polarization-entangled photon states in a non-Markovian environment. Using an all-optical experimental ...setup, we show that entanglement can be revived even after it suffers from sudden death. A maximally revived state is shown to violate a Bell's inequality with 4.1 standard deviations which verifies its quantum nature. The revival phenomenon observed in this experiment provides an intriguing perspective on entanglement dynamics.
Objective
To identify clinical characteristics and risk factors related to the progression of interstitial lung disease (ILD) in patients with primary Sjögren’s syndrome (pSS).
Methods
In this ...single-centered, retrospective study, a total of 83 identified pSS-ILD patients with relatively complete clinical data were finally enrolled. Clinical symptoms, laboratory data, high-resolution computed tomography (HRCT), and pulmonary function test (PFT) results were collected. A logistic regression analysis was performed to determine the independent risk factors for ILD progression, and a nomogram was plotted to construct a predictive model.
Results
The prevalence of pSS-ILD in our study was 18.89%. Among the 83 enrolled patients, 32 (38.6%) underwent ILD progression. The characteristic features associated with the progression of ILD included male sex, non-sicca onset, reticular pattern on HRCT, higher levels of baseline lactic dehydrogenase (LDH), and low baseline forced vital capacity (FVC). The results of multivariate logistic regression indicated that LDH (OR 1.008,
p
= 0.030) was an independent risk factor for ILD progression, while sicca onset (OR 0.254,
p
= 0.044) and FVC (OR 0.952,
p
= 0.003) were protective factors for ILD progression. A simple predictive model for ILD progression in pSS was developed and validated.
Conclusion
pSS patients with non-sicca onset, high baseline LDH level, and low baseline FVC were at higher risk of ILD progression.
Key Points
• Male sex and reticular pattern in HRCT are more common in pSS patients with progressive ILD compared to those with stable ILD.
• Non-sicca onset, high baseline LDH level, and low baseline FVC are independent risk factors of pSS-ILD progression.
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