Hepatoprotective effect of Fufang-Huanglu oral liquid on α- naphthylisothiocyanate-induced hepatitis jaundice in mice

Purpose: To investigate the effect of Fufang-Huanglu Oral Liquid (HOL) on hepatitis jaundice in mice.Methods: A total of 72 mice were divided into 6 groups (n = 12): normal group,  control group (model group), positive-treated group, and 3 HOL treatment groups (7.5, 15 and 30 mL/kg). Mice in normal and control groups received normal saline (20 mL/kg) orally, while positive and HOL-treated mice were orally administered Huganning tablets (1.0 g/kg) and HOL (7.5, 15 and 30 mL/kg), respectively. After 8 days, all mice (except normal group) were orally administered  α-naphthylisothiocyanate (ANIT, 100 mg/kg) to induce hepatitis jaundice, and sacrificed 2 days after drug administration. Serum GPT, GOT and TNF-α, as well as liver index, MDA, SOD and lipid profiles were determined.Results: The results showed that HOL, at all doses, significantly decreased liver index, serum GPT, serum SGOT and serum  TNF-α (p < 0.01). HOL also significantly decreased MDA, total cholesterol, TC and triglycerides, TG (p < 0.01), but increased  liver SOD (p < 0.01). Histological results indicate that HOL ameliorated liver injury induced by ANIT.Conclusion: These results showed that HOL possesses significant hepatoprotective effects against liver injury.Keywords: Fufang-Huanglu Oral Liquid, Hepatoprotective, Mice, Hepatitis, Jaundice, α-Naphthylisothiocyanate, Liver inde

PROTECTIVE ROLE OF XINNAONING TABLET IN ISCHEMIC STROKE IN RAT MODEL

Background: Stroke has been considered as the second leading cause of death worldwide. The survivors of stroke experience different level of impair brain function. In China, Chinese traditional medicine had been widely accepted for stroke therapy and prevention. In this study, we developed Traditional Chinese Medicine based Xinnaoning (peace of heart and brain) Tablet and tested its protective role for ischemic stroke in rat model. Material and Methods: Male Wistar rats (n=60) with 12 weeks old and weight from 180 to 200 gram were randomly divided to five groups (n=12). For the groups with Xinaoning administration, the drug was administrated to rats once per day for 7 consecutive days. The blood clotting time and the thrombus wet weight was measured. Serum samples were collected from each rat for further Measurement of biochemical indicators. Results: Our results demonstrated that Xinnaoning tablet reduced lactate acid (LD) level and increased lactic acid dehydrogenase (LDH) in cerebral ischemia model as well as reduced the infarct size caused by stroke. Besides, evaluation of the level of different ATPases suggested Xinnaoning tablet could modulate ATPases activity and confer a protective role in brain. Moreover, analysis indicated Xinnaoning tablet have the anti-coagulation effect in vivo which may contribute to the protection of ischemia. Conclusion: Our findings suggest that Xinnaoning tablet may be a potential way for cerebral ischemia prevention

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Facile Preparation of Core–Shell Fe₃O₄@Polypyrrole Composites with Superior Electromagnetic Wave Absorption Properties

Core–shell Fe₃O₄@polypyrrole (PPy) composites with excellent electromagnetic wave absorption properties have been prepared by a sequential process of etching, polymerization, and replication. Templating from pre-prepared Fe₃O₄ microspheres, ferric ions were released from the skin layer of the microspheres by acid etching and initiated the oxidative polymerization of pyrrole in suit. The morphological and textural evolution of core–shell Fe₃O₄@PPy composites depending on etching time was investigated by scanning and transmission electron microscope. A maximum reflection loss of as much as −41.9 dB (>99.99% absorption) at 13.3 GHz with a matching layer thickness of 2.0 mm was achieved when the etching time was 5 min. In comparison with other conductive polymer-based core–shell composites reported previously, the Fe₃O₄@PPy composites in this study not only possess better reflection loss performance but also demonstrate a wider effective absorption bandwidth (<−10.0 dB) over the entire Ku band (12.0–18.0 GHz). The excellent electromagnetic wave absorption properties of the core–shell Fe₃O₄@PPy composites are mainly attributed to the enhanced dielectric loss from the PPy shell

Hierarchically Porous Carbons Derived from Biomasses with Excellent Microwave Absorption Performance

A variety of biomass-based carbon materials with two-level porous structure have been successfully prepared by one-step carbonization process. The first level of microscale pores templates from the inherent porous tissues, while the second one of nanopores is produced by the in situ etching by the embedded alkaline metal elements. The superimposed effect of nano and microscale pores endows the hierarchically porous carbons (HPCs) with excellent microwave absorption (MA) performance. Among them, the spinach-derived HPC exhibits a maximum reflection loss of −62.2 dB and a broad effective absorption bandwidth of 7.3 GHz. Particularly, this excellent MA performance can be reproduced using the biomass materials belonging to different families, harvested seasons, and origins, indicating a green and sustainable process. These encouraging findings shed the insights on the preparation of biomass-derived microwave absorbents with promising practical applications

Host EPAC1 Modulates Rickettsial Adhesion to Vascular Endothelial Cells via Regulation of ANXA2 Y23 Phosphorylation

Introduction: Intracellular cAMP receptor exchange proteins directly activated by cAMP 1 (EPAC1) regulate obligate intracellular parasitic bacterium rickettsial adherence to and invasion into vascular endothelial cells (ECs). However, underlying precise mechanism(s) remain unclear. The aim of the study is to dissect the functional role of the EPAC1-ANXA2 signaling pathway during initial adhesion of rickettsiae to EC surfaces. Methods: In the present study, an established system that is anatomically based and quantifies bacterial adhesion to ECs in vivo was combined with novel fluidic force microscopy (FluidFM) to dissect the functional role of the EPAC1-ANXA2 signaling pathway in rickettsiae–EC adhesion. Results: The deletion of the EPAC1 gene impedes rickettsial binding to endothelium in vivo. Rickettsial OmpB shows a host EPAC1-dependent binding strength on the surface of a living brain microvascular EC (BMEC). Furthermore, ectopic expression of phosphodefective and phosphomimic mutants replacing tyrosine (Y) 23 of ANXA2 in ANXA2-knock out BMECs results in different binding force to reOmpB in response to the activation of EPAC1. Conclusions: EPAC1 modulates rickettsial adhesion, in association with Y23 phosphorylation of the binding receptor ANXA2. Underlying mechanism(s) should be further explored to delineate the accurate role of cAMP-EPAC system during rickettsial infection

Cell-Type Apoptosis in Lung during SARS-CoV-2 Infection

The SARS-CoV-2 pandemic has inspired renewed interest in understanding the fundamental pathology of acute respiratory distress syndrome (ARDS) following infection. However, the pathogenesis of ARDS following SRAS-CoV-2 infection remains largely unknown. In the present study, we examined apoptosis in postmortem lung sections from COVID-19 patients and in lung tissues from a non-human primate model of SARS-CoV-2 infection, in a cell-type manner, including type 1 and 2 alveolar cells and vascular endothelial cells (ECs), macrophages, and T cells. Multiple-target immunofluorescence assays and Western blotting suggest both intrinsic and extrinsic apoptotic pathways are activated during SARS-CoV-2 infection. Furthermore, we observed that SARS-CoV-2 fails to induce apoptosis in human bronchial epithelial cells (i.e., BEAS2B cells) and primary human umbilical vein endothelial cells (HUVECs), which are refractory to SARS-CoV-2 infection. However, infection of co-cultured Vero cells and HUVECs or Vero cells and BEAS2B cells with SARS-CoV-2 induced apoptosis in both Vero cells and HUVECs/BEAS2B cells but did not alter the permissiveness of HUVECs or BEAS2B cells to the virus. Post-exposure treatment of the co-culture of Vero cells and HUVECs with a novel non-cyclic nucleotide small molecule EPAC1-specific activator reduced apoptosis in HUVECs. These findings may help to delineate a novel insight into the pathogenesis of ARDS following SARS-CoV-2 infection

Annexin A2 depletion exacerbates the intracerebral microhemorrhage induced by acute rickettsia and Ebola virus infections.

Intracerebral microhemorrhages (CMHs) are small foci of hemorrhages in the cerebrum. Acute infections induced by some intracellular pathogens, including rickettsia, can result in CMHs. Annexin a2 (ANXA2) has been documented to play a functional role during intracellular bacterial adhesion. Here we report that ANXA2-knockout (KO) mice are more susceptible to CMHs in response to rickettsia and Ebola virus infections, suggesting an essential role of ANXA2 in protecting vascular integrity during these intracellular pathogen infections. Proteomic analysis via mass spectrometry of whole brain lysates and brain-derived endosomes from ANXA2-KO and wild-type (WT) mice post-infection with R. australis revealed that a variety of significant proteins were differentially expressed, and the follow-up function enrichment analysis had identified several relevant cell-cell junction functions. Immunohistology study confirmed that both infected WT and infected ANXA2-KO mice were subjected to adherens junctional protein (VE-cadherin) damages. However, key blood-brain barrier (BBB) components, tight junctional proteins ZO-1 and occludin, were disorganized in the brains from R. australis-infected ANXA2-KO mice, but not those of infected WT mice. Similar ANXA2-KO dependent CMHs and fragments of ZO-1 and occludin were also observed in Ebola virus-infected ANXA2-KO mice, but not found in infected WT mice. Overall, our study revealed a novel role of ANXA2 in the formation of CMHs during R. australis and Ebola virus infections; and the underlying mechanism is relevant to the role of ANXA2-regulated tight junctions and its role in stabilizing the BBB in these deadly infections

Measurement of prompt D+D^+ and Ds+D^+_{s} production in pPbp\mathrm{Pb} collisions at sNN=5.02 \sqrt {s_{\mathrm{NN}}}=5.02\,TeV

International audienceThe production of prompt $D^+$ and $D^+_{s}$ mesons is studied in proton-lead collisions at a centre-of-mass energy of $\sqrt {s_{\mathrm{NN}}}=5.02\,$TeV. The data sample corresponding to an integrated luminosity of $(1.58\pm0.02)\mathrm{nb}^{-1}$ is collected by the LHCb experiment at the LHC. The differential production cross-sections are measured using $D^+$ and $D^+_{s}$ candidates with transverse momentum in the range of $0<p_{\mathrm{T}} <14\,\mathrm{GeV}/c$ and rapidities in the ranges of $1.5<y^*<4.0$ and $-5.0<y^*<-2.5$ in the nucleon-nucleon centre-of-mass system. For both particles, the nuclear modification factor and the forward-backward production ratio are determined. These results are compared with theoretical models that include initial-state nuclear effects. In addition, measurements of the cross-section ratios between $D^+$, $D^+_{s}$ and $D^0$ mesons are presented, providing a baseline for studying the charm hadronization in lead-lead collisions at LHC energies

Search for Bc+→π+μ+μ−B_c^+\to\pi^+\mu^+\mu^- decays and measurement of the branching fraction ratio B(Bc+→ψ(2S)π+)/B(Bc+→J/ψπ+){\cal B}(B_c^+\to\psi(2S)\pi^+)/{\cal B}(B_c^+\to J/\psi \pi^+)

International audienceThe first search for nonresonant $B_c^+\to\pi^+\mu^+\mu^-$ decays is reported. The analysis uses proton-proton collision data collected with the LHCb detector between 2011 and 2018, corresponding to an integrated luminosity of 9 fb$^{-1}$. No evidence for an excess of signal events over background is observed and an upper limit is set on the branching fraction ratio ${\cal B}(B_c^+\to\pi^+\mu^+\mu^-)/{\cal B}(B_c^+\to J/\psi \pi^+) < 2.1\times 10^{-4}$ at $90\%$ confidence level. Additionally, an updated measurement of the ratio of the $B_c^+\to\psi(2S)\pi^+$ and $B_c^+\to J/\psi \pi^+$ branching fractions is reported. The ratio ${\cal B}(B_c^+\to\psi(2S)\pi^+)/{\cal B}(B_c^+\to J/\psi \pi^+)$ is measured to be $0.254\pm 0.018 \pm 0.003 \pm 0.005$, where the first uncertainty is statistical, the second systematic, and the third is due to the uncertainties on the branching fractions of the leptonic $J/\psi$ and $\psi(2S)$ decays. This measurement is the most precise to date and is consistent with previous LHCb results