We report phase-programmable Gaussian boson sampling (GBS) which produces up to 113 photon detection events out of a 144-mode photonic circuit. A new high-brightness and scalable quantum light source ...is developed, exploring the idea of stimulated emission of squeezed photons, which has simultaneously near-unity purity and efficiency. This GBS is programmable by tuning the phase of the input squeezed states. The obtained samples are efficiently validated by inferring from computationally friendly subsystems, which rules out hypotheses including distinguishable photons and thermal states. We show that our GBS experiment passes a nonclassicality test based on inequality constraints, and we reveal nontrivial genuine high-order correlations in the GBS samples, which are evidence of robustness against possible classical simulation schemes. This photonic quantum computer, Jiuzhang 2.0, yields a Hilbert space dimension up to ∼ 1043, and a sampling rate ∼ 1024 faster than using brute-force simulation on classical supercomputers.
Liver sinusoidal endothelial cells (LSECs) critically regulate liver homeostasis and diseases through angiocrine factors. Notch is critical in endothelial cells (ECs). In the current study, Notch ...signaling was activated by inducible EC‐specific expression of the Notch intracellular domain (NIC). We found that endothelial Notch activation damaged liver homeostasis. Notch activation resulted in decreased fenestration and increased basement membrane, and a gene expression profile with decreased LSEC‐associated genes and increased continuous EC‐associated genes, suggesting LSEC dedifferentiation. Consistently, endothelial Notch activation enhanced hepatic fibrosis (HF) induced by CCl4. Notch activation attenuated endothelial nitric oxide synthase (eNOS)/soluble guanylate cyclase (sGC) signaling, and activation of sGC by 3‐(5′‐hydroxymethyl‐2′‐furyl)‐1‐benzylindazole (YC‐1) reversed the dedifferentiation phenotype. In addition, Notch activation subverted the hepatocyte‐supporting angiocrine profile of LSECs by down‐regulating critical hepatocyte mitogens, including Wnt2a, Wnt9b, and hepatocyte growth factor (HGF). This led to compromised hepatocyte proliferation under both quiescent and regenerating conditions. Whereas expression of Wnt2a and Wnt9b was dependent on eNOS‐sGC signaling, HGF expression was not rescued by the sGC activator, suggesting heterogeneous mechanisms of LSECs to maintain hepatocyte homeostasis. Conclusion: Endothelial Notch activation results in LSEC dedifferentiation and accelerated liver fibrogenesis through eNOS‐sGC signaling, and alters the angiocrine profile of LSECs to compromise hepatocyte proliferation and liver regeneration (LR). (Hepatology 2018).
Depression is a devastating disorder with a combination of diverse symptoms such as low self-esteem, lack of motivation, anhedonia, loss of appetite, low energy, and discomfort without a clear cause. ...Depression has been suggested to be the result of maladaptive changes in specific brain circuits. Recently, the lateral habenula (LHb) has emerged as a key brain region in the pathophysiology of depression. Increasing evidence from rodent, non-human primate and human studies indicates that the aberrant activity of the LHb is associated with depressive symptoms such as helplessness, anhedonia, and excessive negative focus. Revealing the molecular, cellular and circuit properties of the LHb will help explain how abnormalities in LHb activity are linked to depressive disorders, and shed light on developing novel strategies for depression treatment.
An ultrasensitive electrochemiluminescence (ECL) biosensor was proposed based on a closed bipolar electrode (BPE) for the detection of alkaline phosphatase (ALP). For most of the BPE–ECL biosensors, ...an effective signal amplification strategy was the key to enhance the sensitivity of the system. Herein, the signal amplification strategy of the enzyme catalysis was utilized in the BPE–ECL system. Au nanoparticles (NPs) were electrodeposited on the cathode surface of the ITO electrode to improve the stability and sensitivity of the signal. Compared with the previous BPE–ECL biosensors, the sensitivity was increased by at least 3 orders of magnitude. The biosensor showed high sensitivity and specificity of ALP detection with a detection limit of as low as 3.7 aM. Besides, it was further applied to the detection of ALP in different types of cells and successfully realized ALP detection in single Hep G2 cell, which had a huge application prospect in single biomolecule detection or single cell analysis.
In situ monitoring of the agglomeration/aggregation process of nanoparticles (NPs) is crucial because it seriously affects cell entry, biosafety, catalytic performance of NPs, and so on. ...Nevertheless, it remains hard to monitor the solution phase agglomeration/aggregation of NPs via conventional techniques such as electron microscopy, which requires sample pretreatment and cannot represent native state NPs in solution. Considering that single-nanoparticle electrochemical collision (SNEC) is powerful to detect NPs in solution at the single-particle level, and the current lifetime, which refers to the time that current intensity decays to 1/e of the original value, is skilled in distinguishing different sized NPs, herein, a current lifetime-based SNEC has been developed to distinguish a single Au NP (d = 18 nm) from its agglomeration/aggregation. Based on this, the agglomeration/aggregation process of small-sized NPs and the discrimination of agglomeration vs aggregation have been carefully investigated at the single-particle level. Results showed that the agglomeration/aggregation of Au NPs (d = 18 nm) in 0.8 mM HClO4 climbed from 19% to 69% over two hours, whereas there was no visible granular sediment, and Au NPs tended to agglomerate rather than aggregate irreversibly under normal conditions. Hence, the proposed current lifetime-based SNEC could serve as a complementary method to in situ monitor the agglomeration/aggregation of small-sized NPs in solution at the single-particle level and provide effective guidance for the practical application of NPs.
Influenza A virus （IAV） infects the respiratory tract in humans and causes significant morbidity and mortality worldwide each year. Aggressive inflammation, known as a cytokine storm, is thought to ...cause most of the damage in the lungs during IAV infection. Dysfunctional coagulation is a common complication in pathogenic influenza, manifested by lung endothelial activation, vascular leak, disseminated intravascular coagulation and pulmonary microembolism. Importantly, emerging evidence shows that an uncontrolled coagulation system, including both the cellular （endothelial cells and platelets） and protein （coagulation factors, anticoagulants and fibrinolysis proteases） components, contributes to the pathogenesis of influenza by augmenting viral replication and immune pathogenesis. In this review, we focus on the underlying mechanisms of the dysfunctional coagulatory response in the Dathogenesis of IAV.
Background
DL‐3‐n‐butylphthalide (NBP) has been approved to be effective in improving cognitive deficits. The aim of the current study was to determine whether NBP protects against cognitive deficits ...in a rat model of vascular dementia (VD) induced by chronic cerebral hypoperfusion (CCH) by regulating the sonic hedgehog (Shh)/patched1 (Ptch1) pathway and endoplasmic reticulum stress (ERS)‐related markers.
Methods
Adult male Sprague‐Dawley rats were subjected to permanent bilateral occlusion of the common carotid arteries (2VO) to established the model of VD. These rats were randomly divided into five groups: sham, model, NBP30 (30 mg/kg), NBP
60 (60 mg/kg), and NBP
120 (120 mg/kg) groups. The Morris water maze test was used to assess for cognitive function at 4 weeks after operation.
Results
NBP significantly alleviated spatial learning and memory impairment, and inhibited the loss of neurons in the CA1 region of the hippocampus. Western blot analysis and real‐time quantitative polymerase chain reaction analysis revealed that plasticity‐related synaptic markers and the Shh/Ptch1 pathway significantly increased in the NBP treated groups, while ERS‐related markers decreased.
Conclusion
The results of the current study prove that the Shh/Ptch1 pathway plays an essential role in the model of VD. NBP had protective effects on cognitive impairment induced by CCH. This mechanism was associated with ERS and the Shh/Ptch1 pathway. Meanwhile, the Shh/Ptch1 pathway and ERS may interact with each other.
The N-methyl-d-aspartate receptor (NMDAR) antagonist ketamine has attracted enormous interest in mental health research owing to its rapid antidepressant actions, but its mechanism of action has ...remained elusive. Here we show that blockade of NMDAR-dependent bursting activity in the 'anti-reward center', the lateral habenula (LHb), mediates the rapid antidepressant actions of ketamine in rat and mouse models of depression. LHb neurons show a significant increase in burst activity and theta-band synchronization in depressive-like animals, which is reversed by ketamine. Burst-evoking photostimulation of LHb drives behavioural despair and anhedonia. Pharmacology and modelling experiments reveal that LHb bursting requires both NMDARs and low-voltage-sensitive T-type calcium channels (T-VSCCs). Furthermore, local blockade of NMDAR or T-VSCCs in the LHb is sufficient to induce rapid antidepressant effects. Our results suggest a simple model whereby ketamine quickly elevates mood by blocking NMDAR-dependent bursting activity of LHb neurons to disinhibit downstream monoaminergic reward centres, and provide a framework for developing new rapid-acting antidepressants.
Ubiquitous micro(nano)plastics (MNPs) are emerging environmental pollutants, which pose a potential threat to human health. When MNPs enter the blood circulatory system, vascular endothelium is one ...of the most important target organs that directly interact with the MNPs. However, little is known about the cytotoxicity of MNPs to vascular endothelial cells. In this study, we investigated the uptake and cytotoxic effects of polystyrene MNPs with a particle size of 1 μm (1‐μm PS‐MNPs) on human umbilical vein endothelial cells (HUVECs) in vitro. Our study found that interaction between HUVECs and 1‐μm PS‐MNPs was at a very low level. Even at the high exposure concentration of 25 μg/mL, the percentage of HUVECs combined with fluorescent 1‐μm PS‐MNPs was only 3.80% using flow cytometry analysis. Moreover, there were no significant differences in inflammation, autophagy, reactive oxygen species (ROS) level, lactate dehydrogenase (LDH) release, and adhesion molecule expression following exposure to 1‐μm PS‐MNPs (5, 10, and 25 μg/mL) for 48 h, except for a remarkable decrease in cell viability at the extremely high concentration of 100 μg/mL. Herein, 1‐μm PS‐MNPs showed a low level of acute toxicity to HUVECs in vitro, and we expect these results contribute to the further risk assessment of MNPs on human health.
Polystyrene micro(nano)plastics with a diameter of 1 μm (1‐μm PS‐MNPs) interacted weakly with human umbilical vein endothelial cells (HUVECs), and there was no significant effect on autophagy, inflammation, reactive oxygen species (ROS) level, lactate dehydrogenase (LDH) release, and adhesion molecule expression following exposure to 1‐μm PS‐MNPs (5,10, and 25 μg/mL) in HUVECs, except for a detectable decrease in cell viability at extremely high exposure concentration (100 μg/mL).
Biogenic amines in wine: a review Guo, Yan-Yun; Yang, Yan-Ping; Peng, Qian ...
International journal of food science & technology,
July 2015, Letnik:
50, Številka:
7
Journal Article
Recenzirano
Summary
Biogenic amines are formed from precursor amino acids, mainly by the microbial decarboxylation. The presence of these compounds plays a vital role in oenology because high amounts of them can ...lead to health problems. Thus, the origin, detection, and quantity of biogenic amines in wine are extremely important for winemaking. This study, focusing on the articles of latest 5 years, not only reviews the analytical methods used for the determination of biogenic amines but also describes the source of biogenic amines from the perspective of microbiological and oenological factors and summarises the strategies for the degradation of amines. The information presented in this review is important to alert about the inadequate quality of wine products, and efforts from the entire productive chain and the government are required to attain consumer safety.
Biogenic amines are formed from precursor amino acids, mainly by the microbial decarboxylation. In this review, five aspects are proposed to analysis the content of biogenic amines in wine.
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