The Evaluation of Toxicity Induced by Psoraleae Fructus in Rats Using Untargeted Metabonomic Method Based on UPLC-Q-TOF/MS

Psoraleae Fructus is the dry and mature fruit of leguminous plant Psoralea corylifolia L., with the activity of warming kidney and enhancing yang, warming spleen, and other effects. However, large doses can cause liver and kidney toxicity. Therefore, it is necessary to evaluate the toxicity of Psoraleae Fructus systematically. Although traditional biochemical indicators and pathological tests have been used to evaluate the safety of drug, these methods lack sensitivity and specificity, so a fast and sensitive analytical method is urgently needed. In this study, an ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) method was used to analyze the metabolic profiles of rat plasma. The changes of metabolites in plasma samples were detected by partial least squares-discriminant analysis (PLS-DA). Compared with the control group, after 7 days of administration, the pathological sections showed liver and kidney toxicity, and the metabolic trend was changed. Finally, 13 potential biomarkers related to the toxicity of Psoraleae Fructus were screened. The metabolic pathways involved were glycerol phospholipids metabolism, amino acid metabolism, energy metabolism, and so forth. The discovery of these biomarkers laid a foundation for better explaining the hepatotoxicity and nephrotoxicity of Psoraleae Fructus and provided a guarantee for its safety evaluation

The Ets Transcription Factor GABP Is a Component of the Hippo Pathway Essential for Growth and Antioxidant Defense

这是周大旺教授继2009年首次发现了Hippo信号通路在哺乳动物中控制器官大小及肿瘤发生具有重要作用后的又一重大研究成果，该研究系统阐述了 YAP基因在转录调控水平上的的调控机理，进一步完善了人们对Hippo信号通路的认识，也为由YAP调控异常所引发的癌症提供了一个潜在的治疗靶点。 该论文的第一作者为博士生吴黉坦和硕士生肖玉波和张世浩, 通讯作者是周大旺教授和陈兰芬副教授，该工作是与厦门市中医院、中山医院和医学高等专科学校等单位合作完成的。周大旺教授是中央首批“青年千人计划”入选者并获得国家首批“优秀青年科学基金”资助。The transcriptional coactivator Yes-associated protein (YAP) plays an important role in organ-size control and tumorigenesis. However, how Yap gene expression is regulated remains unknown. This study shows that the Ets family member GABP binds to the Yap promoter and activates YAP transcription. The depletion of GABP downregulates YAP, resulting in a G1/S cell-cycle block and increased cell death, both of which are substantially rescued by reconstituting YAP. GABP can be inactivated by oxidative mechanisms, and acetaminophen-induced glutathione depletion inhibits GABP transcriptional activity and depletes YAP. In contrast, activating YAP by deleting Mst1/Mst2 strongly protects against acetaminophen-induced liver injury. Similar to its effects on YAP, Hippo signaling inhibits GABP transcriptional activity through several mechanisms. In human liver cancers, enhanced YAP expression is correlated with increased nuclear expression of GABP. Therefore, we conclude that GABP is an activator of Yap gene expression and a potential therapeutic target for cancers driven by YAP

A Search for Light Fermionic Dark Matter Absorption on Electrons in PandaX-4T

We report a search on a sub-MeV fermionic dark matter absorbed by electrons with an outgoing active neutrino using the 0.63 tonne-year exposure collected by PandaX-4T liquid xenon experiment. No significant signals are observed over the expected background. The data are interpreted into limits to the effective couplings between such dark matter and electrons. For axial-vector or vector interactions, our sensitivity is competitive in comparison to existing astrophysical bounds on the decay of such dark matter into photon final states. In particular, we present the first direct detection limits for an axial-vector (vector) interaction which are the strongest in the mass range from 25 to 45 (35 to 50) keV/c$^2$

Nitrogen-Doped Core-Shell Mesoporous Carbonaceous Nanospheres for Effective Removal of Fluorine in Capacitive Deionization

Fluorine pollution of wastewater is a global environmental problem. Capacitive deionization has unique advantages in the defluorination of fluorine-containing wastewater; however, the low electrosorption capacity significantly restricts its further development. To overcome this limitation, nitrogen-doped core-shell mesoporous carbonaceous nanospheres (NMCS) were developed in this study based on structural optimization and polarity enhancement engineering. The maximal electrosorption capacity of NMCS for fluorine reached 13.34 mg g−1, which was 24% higher than that of the undoped counterpart. NMCS also indicated excellent repeatability evidenced by little decrease of electrosorption capacity after 10 adsorption-regeneration cycles. According to material and electrochemical measurements, the doping of nitrogen into NMCS resulted in the improvement of physicochemical properties such as conductivity and wettability, the amelioration of pore structure and the transformation of morphology from yolk-shell to core-shell structure. It not only facilitated ion transportation but also improved the available adsorption sites, and thus led to enhancement of the defluorination performance of NMCS. The above results demonstrated that NMCS would be an excellent electrode material for high-capacity defluorination in CDI systems

Measurement-device-independent quantum secure direct communication

Quantum secure direct communication (QSDC) is a unique technique, which supports the secure transmission of confidential information directly through a quantum channel without the need for a secret key and for ciphertext. Hence this secure communication protocol fundamentally differs from its conventional counterparts. In this article, we report the first measurement-device-independent (MDI) QSDC protocol relying on sequences of entangled photon pairs and single photons. Explicitly, it eliminates the security loopholes associated with the measurement device. Additionally, this MDI technique is capable of doubling the communication distance of its conventional counterpart operating without using our MDI technique. We also conceive a protocol associated with linear optical Bell-basis measurements, where only two of the four Bell-basis states could be measured. When the number of qubits in a sequence reduces to 1, the MDI-QSDC protocol degenerates to a deterministic MDI quantum key distribution protocol

Comparative study on hemodynamic environments around patient-specific carotid atherosclerotic plaques with different symmetrical features

Atherosclerotic plaque near the carotid sinus is a key risk factor for ischemic stroke. Although disturbed hemodynamic environments around atherosclerotic plaque had been investigated in many studies, the effect of their symmetrical features, especially longitudinal asymmetrical characteristics, had not been comparatively studied. In this study, three-dimensional carotid bifurcation models were established based on CT images of three patients with 50% stenosis and with different symmetrical features of carotid atherosclerotic plaques including concentric plaque, eccentric plaque, or eccentric longitudinal asymmetrical plaque. A healthy subject was chosen as the control. Wall shear stress (WSS) and oscillating shear index in the regions of upstream, downstream, downstream shoulders and regions around the point of maximum stenosis were analyzed. The results indicated that the maximum WSS around the eccentric longitudinal asymmetrical plaque were 8.6 times larger than that of the eccentric plaque and 1.9 times larger than that of the concentric plaque. And the distributions of WSS and OSI around the eccentric longitudinal asymmetric plaque were more disordered than those of the others. Our results highlighted the risk of the eccentric longitudinal asymmetrical plaque on plaque development and rupture and might provide a new index for evaluating the development of atherosclerosis

Rapid Classification and Identification of Chemical Components of Schisandra Chinensis by UPLC-Q-TOF/MS Combined with Data Post-Processing

Schisandra chinensis (known in Chinese as WuWeiZi, WWZ) has observable effects such as astringing the lung to stop coughs, arresting sweating, preserving semen and preventing diarrhea. The major components of WWZ include lignans, triterpenoids, organic acids and fatty acids. In this paper, a reliable method for the rapid identification of multiple components in WWZ by their characteristic fragments and neutral losses using UPLC-Q-TOF/MS technology was developed. After review of the literature and some reference experiments, the fragmentation pattern of several compounds were studied and summarized. Then, according to the corresponding characteristic fragments coupled with neutral losses in the positive or negative ion mode produced by different types of substances a rapid identification of target compounds was achieved. Finally, a total of 30 constituents of WWZ were successfully identified, including 15 lignans, nine triterpenoids, three organic acids and three fatty acids. The method established in this study not only provides a comprehensive analysis of the chemical ingredients of WWZ, providing a basis for further phytochemical studies on WWZ but also provides a more efficient way to solve the problem of identification of complex chemical constituents in traditional Chinese medicines

The Characterization of OXA-232 Carbapenemase-Producing ST437 Klebsiella pneumoniae in China

Carbapenem-resistant Klebsiella pneumoniae (CRKP) was epidemic around the world and become a global threat to public health. The most important carbapenem-resistant mechanism is producing carbapenemases, especially Klebsiella pneumoniae carbapenemase (KPC), which is prevalent in the international clonal complex CC11. The high-risk multidrug-resistant CC11 is widespread worldwide, and KPC-producing and (New Delhi metallo) NDM-producing strains had been reported in this clonal complex before; moreover, cases with the CC11 strain faced more severe forms of drug resistance and treatment challenges than other clonal complexes. In this study, we identified an OXA-232-producing ST437 Klebsiella pneumoniae isolate in China, which belonged to CC11. The isolate was resistant to β-lactams, aminoglycosides, and fluoroquinolones but susceptible to fosfomycin, tigecycline, and colistin. The blaOXA-232 gene was located on a 6141 bp ColKP3-type nonconjugative plasmid, and the plasmid was transformed by chemical transformation successfully. This is the first report of OXA-232-producing ST437 K. pneumoniae in China, a new clone of high-risk multidrug-resistant CC11