A portable device for studying the effects of fluid flow on degradation properties of biomaterials inside cell incubators.

A portable device was designed and constructed for studying the properties of biomaterials in physiologically relevant fluids under controllable flow conditions that closely simulate fluid flow inside the body. The device can fit entirely inside a cell incubator; and, thus, it can be used directly under standard cell culture conditions. An impedance-driven pump was built in the sterile flow loop to control the flow rates of fluids, which made the device small and portable for easy deployment in the incubator. To demonstrate the device functions, magnesium (Mg) as a representative biodegradable material was tested in the flow device for immersion degradation under flow versus static conditions, while the flow module was placed inside a standard cell incubator. The flow rate was controlled at 0.17 ± 0.06 ml/s for this study; and, the flow rate is adjustable through the controller module outside of incubators for simulating the flow rates in the ranges of blood flow in human artery (0.05 ∼0.43 ml/s) and vein (0.02 ∼0.08 ml/s). Degradation of Mg under flow versus static conditions was characterized by measuring the changes of sample mass and thickness, and Mg2+ ion concentrations in the immersion media. Surface chemistry and morphology of Mg after immersion under flow versus static conditions were compared. The portable impedance-driven flow device is easy to fit inside an incubator and much smaller than a peristaltic pump, providing a valuable solution for studying biomaterials and implants (e.g. vascular or ureteral stents) in body fluids under flow versus static conditions with or without cells

The current landscape of the antimicrobial peptide melittin and its therapeutic potential

Melittin, a main component of bee venom, is a cationic amphiphilic peptide with a linear α-helix structure. It has been reported that melittin can exert pharmacological effects, such as antitumor, antiviral and anti-inflammatory effects in vitro and in vivo. In particular, melittin may be beneficial for the treatment of diseases for which no specific clinical therapeutic agents exist. Melittin can effectively enhance the therapeutic properties of some first-line drugs. Elucidating the mechanism underlying melittin-mediated biological function can provide valuable insights for the application of melittin in disease intervention. However, in melittin, the positively charged amino acids enables it to directly punching holes in cell membranes. The hemolysis in red cells and the cytotoxicity triggered by melittin limit its applications. Melittin-based nanomodification, immuno-conjugation, structural regulation and gene technology strategies have been demonstrated to enhance the specificity, reduce the cytotoxicity and limit the off-target cytolysis of melittin, which suggests the potential of melittin to be used clinically. This article summarizes research progress on antiviral, antitumor and anti-inflammatory properties of melittin, and discusses the strategies of melittin-modification for its future potential clinical applications in preventing drug resistance, enhancing the selectivity to target cells and alleviating cytotoxic effects to normal cells

The Major Controlling Factors Analysis of Hydrocarbon Accumulation on the Gentle Slope Belt of the Southeastern Liaodong Bay Depression

Oil and gas discovery in the Liaodong Bay Depression is mainly distributed in the steep slope, the uplift and the sag zone at current situation. The reservoir developed on southeastern gentle slope zone is the first discovery in this area, which has great significance to the study of the gentle slope zone hydrocarbon accumulation regularity. Based on the analysis of the hydrocarbon accumulation condition of the gentle slope zone, the major controlling factors and hydrocarbon accumulation pattern of the gentle slope zone are summarized. It shows that the gentle slope belt has the superior accumulation conditions, where develops Lithological-tectonics traps and lithological traps Controlled by fracture and provenance. The source rock circumstance is advantageous too, because the gentle slope zone is close to the hydrocarbon-rich Liaozhong sag. The mudstone in Dongying formation(Ed) and the first section of Shahejie formation (Es1) and the sandstone in the second member of Shahejie formation (Es2) are form into a good reservoir cap association. Hydrocarbon accumulation in the gentle slope belt is mainly controlled by 3 factors: the development of the reservoirs in the Es2 is controlled by the valley-slope break coupling; the migration of oil and gas is controlled by “Fault-unconformity-sandbody”(FUS) long-range efficient migration system; reservoir physical properties and oil and gas test capacity are controlled by sedimentary facies differences. There are two reservoir models: lithology - tectonics and lithology

Analysis of Intestinal Injuries Induced by Ricin in Vitro Using SPR Technology and MS Identification

The present study found that ricin toxicity did not only manifest itself as inhibition of protein synthesis, but also induced apoptosis of immune cells and played an extremely significant role in intestinal injury. In this report, we describe a novel method to estimate binding events occurring on intestinal brush border membranes (BBM) based on SPR technology in an attempt to mimic the real intestinal surface capable of interacting physically and/or actively with certain biological molecules. Combined with HPCE-ESI-MS indentification, we obtained 28 kinds of proteins in BBM that interacted with ricin

Adenosine stimulates the basolateral 50 pS K+ channel in renal proximal tubule via adenosine-A1 receptor

Background: The basolateral potassium channels play an important role in maintaining the membrane transport in the renal proximal tubules (PT) and adenosine receptors have been shown to regulate the trans-epithelial Na+ absorption in the PT. The aim of the present study is to explore whether adenosine also regulates the basolateral K+ channel of the PT and to determine the adenosine receptor type and the signaling pathway which mediates the effect of adenosine on the K+ channel.Methods: We have used the single channel recording to examine the basolateral K+ channel activity in the proximal tubules of the mouse kidney. All experiments were performed in cell-attached patches.Results: Single channel recording has detected a 50 pS inwardly-rectifying K+ channel with high channel open probability and this 50 pS K+ channel is a predominant type K+ channel in the basolateral membrane of the mouse PT. Adding adenosine increased 50 pS K+ channel activity in cell-attached patches, defined by NPo (a product of channel Numbers and Open Probability). The adenosine-induced stimulation of the 50 pS K+ channel was absent in the PT pretreated with DPCPX, a selective inhibitor of adenosine A1 receptor. In contrast, adenosine was still able to stimulate the 50 pS K+ channel in the PT pretreated with CP-66713, a selective adenosine A2 receptor antagonist. This suggests that the stimulatory effect of adenosine on the 50 pS K+ channel of the PT was mediated by adenosine-A1 receptor. Moreover, the effect of adenosine on the 50 pS K+ channel was blocked in the PT pretreated with U-73122 or Calphostin C, suggesting that adenosine-induced stimulation of the 50 pS K+ channels of the PT was due to the activation of phospholipase C (PLC) and protein kinase C (PKC) pathway. In contrast, the inhibition of phospholipase A2 (PLA2) with AACOCF3 or inhibition of protein kinase A (PKA) with H8 failed to block the adenosine-induced stimulation of the 50 pS K+ channel of the PT.Conclusion: We conclude that adenosine activates the 50 pS K+ channels in the basolateral membrane of PT via adenosine-A1 receptor. Furthermore, the effect of adenosine on the 50 pS K+ channel is mediated by PLC-PKC signaling pathway

A solution-processable and ultra-permeable conjugated microporous thermoset for selective hydrogen separation.

The synthesis of a polymer that combines the processability of plastics with the extreme rigidity of cross-linked organic networks is highly attractive for molecular sieving applications. However, cross-linked networks are typically insoluble or infusible, preventing them from being processed as plastics. Here, we report a solution-processable conjugated microporous thermoset with permanent pores of ~0.4 nm, prepared by a simple heating process. When employed as a two-dimensional molecular sieving membrane for hydrogen separation, the membrane exhibits ultrahigh permeability with good selectivity for H2 over CO2, O2, N2, CH4, C3H6 and C3H8. The combined processability, structural rigidity and easy feasibility make this polymeric membrane promising for large-scale hydrogen separations of commercial and environmental relevance

A neutralizing bispecific single-chain antibody against SARS-CoV-2 Omicron variant produced based on CR3022

IntroductionThe constantly mutating SARS-CoV-2 has been infected an increasing number of people, hence the safe and efficacious treatment are urgently needed to combat the COVID-19 pandemic. Currently, neutralizing antibodies (Nabs), targeting the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein are potentially effective therapeutics against COVID-19. As a new form of antibody, bispecific single chain antibodies (BscAbs) can be easily expressed in E. coli and exhibits broad-spectrum antiviral activity.MethodsIn this study, we constructed two BscAbs 16-29, 16-3022 and three single chain variable fragments (scFv) S1-16, S2-29 and S3022 as a comparison to explore their antiviral activity against SARS-CoV-2. The affinity of the five antibodies was characterized by ELISA and SPR and the neutralizing activity of them was analyzed using pseudovirus or authentic virus neutralization assay. Bioinformatics and competitive ELISA methods were used to identify different epitopes on RBD.ResultsOur results revealed the potent neutralizing activity of two BscAbs 16-29 and 16-3022 against SARS-CoV-2 original strain and Omicron variant infection. In addition, we also found that SARS-CoV RBD-targeted scFv S3022 could play a synergistic role with other SARS-CoV-2 RBD-targeted antibodies to enhance neutralizing activity in the form of a BscAb or in cocktail therapies.DiscussionThis innovative approach offers a promising avenue for the development of subsequent antibody therapies against SARSCoV-2. Combining the advantages of cocktails and single-molecule strategies, BscAb therapy has the potential to be developed as an effective immunotherapeutic for clinical use to mitigate the ongoing pandemic

Magnetic Domain Structure in Ferromagnetic Kagome Metal DyMn6Sn6

Two types of magnetic domains, that is, type-I domain belt domain and type-II new stripe domain, are observed in a kagome metal DyMn6Sn6 by microscopic magneto-optic Kerr imaging technique. From 255 to 235 K, the spin reorientation is observed directly in DyMn6Sn6. We analyze the structure of two types of domains through brightness distribution of the images. The type-II domain exists from 235 to 160 K by zero-field cooling (ZFC). At the same time, type-I domain and type-II domain coexist and transform into each other with variation of temperature. Type-II domains can easily transform into type-I domains when the temperature and magnetic field changes, and this process is irreversible. These results demonstrate that the type-I domain is more stable than the type-II domain. The phase diagram of magnetic domains in DyMn6Sn6 is obtained