Mathematical predictions of oxygen availability in micro- and macro-encapsulated human and porcine pancreatic islets

Optimal function of immunoisolated islets requires adequate supply of oxygen to metabolically active insulin producing beta-cells. Using mathematical modeling, we investigated the influence of the pO2 on islet insulin secretory capacity and evaluated conditions that could lead to the development of tissue anoxia, modeled for a 300 μm islet in a 500 μm microcapsule or a 500 μm planar, slab-shaped macrocapsule. The pO2 was used to assess the part of islets that contributed to insulin secretion. Assuming a 500 μm macrocapsule with a 300 μm islet, with oxygen consumption rate (OCR) of 100-300 nmol min-1 mg-1 DNA, islets did not develop any necrotic core. The nonfunctional zone (with no insulin secretion if pO2  < 0.1 mmHg) was 0.3% for human islets (OCR ~100 nmol/min/mg DNA) and 35% for porcine islets (OCR ~300 nmol/min/mg DNA). The OCR of the islet preparation is profoundly affected by islet size, with optimal size of <250 μm in diameter (human) or <150 μm (porcine). Our data suggest that microcapsules afford superior oxygen delivery to encapsulated islets than macrocapsules, and optimal islet function can be achieved by encapsulating multiple, small (<150 μm) islets with OCR of ~100 nmol min-1 mg-1 DNA (human islets) or ~200 nmol min-1 mg-1 DNA (porcine islets)

Effects of ambient temperatures between 5 and 35 °C on energy balance, body mass and body composition in mice

ACKNOWLEDGMENTS This work was partly supported by grants (31670417 and 31870388 to Z.J.Z., and 92057206 to J.R.S) from the National Natural Science Foundation of China and the National Key R&D Program of China (2019YFA0801900 to J.R.S).Peer reviewedPublisher PD

Exosome loaded immunomodulatory biomaterials alleviate local immune response in immunocompetent diabetic mice post islet xenotransplantation

Foreign body response (FBR) to biomaterials compromises the function of implants and leads to medical complications. Here, we report a hybrid alginate microcapsule (AlgXO) that attenuated the immune response after implantation, through releasing exosomes derived from human Umbilical Cord Mesenchymal Stem Cells (XOs). Upon release, XOs suppress the local immune microenvironment, where xenotransplantation of rat islets encapsulated in AlgXO led to >170 days euglycemia in immunocompetent mouse model of Type 1 Diabetes. In vitro analyses revealed that XOs suppressed the proliferation of CD3/CD28 activated splenocytes and CD3+ T cells. Comparing suppressive potency of XOs in purified CD3+ T cells versus splenocytes, we found XOs more profoundly suppressed T cells in the splenocytes co-culture, where a heterogenous cell population is present. XOs also suppressed CD3/CD28 activated human peripheral blood mononuclear cells (PBMCs) and reduced their cytokine secretion including IL-2, IL-6, IL-12p70, IL-22, and TNFα. We further demonstrate that XOs mechanism of action is likely mediated via myeloid cells and XOs suppress both murine and human macrophages partly by interfering with NFκB pathway. We propose that through controlled release of XOs, AlgXO provide a promising new platform that could alleviate the local immune response to implantable biomaterials

Immobilization, Trapping, and Anion Exchange of Perrhenate Ion Using Copper-Based Tripodal Complexes

We describe a multidentate tripodal ligand in which three pendant arms carrying di(2-picolyl)amine units are linked to the ortho positions of a tris(o-xylyl) scaffold, providing N(CH[subscript 2]-o-C[subscript 6]H[subscript 4]CH[subscript 2]N(CH2py)[subscript 2])[subscript 3] (L). Reaction of L with CuCl[subscript 2] in the presence of hexafluorophosphate anion afforded blue cubes of [(CuCl)[subscript 3]L](PF[subscript 6])[subscript 3]·5H[subscript 2]O (1). Crystallographic studies of 1 revealed that the three symmetry-related arms each coordinate a {Cu[superscript II]Cl} unit, and two molecules of 1 are connected to one another through a Cu(μ-Cl)[subscript 2]Cu bridge, extending the molecular structure to form a two-dimensional (2-D) layer. These 2-D layers pack in an ABCABC... fashion with PF[subscript 6]– anions located in between. Reaction of 1 with a stoichiometric amount of perrhenate ion afforded blue plates of [(CuCl)[subscript 3]L](PF[subscript 6])(ReO[subscript 4])[subscript 2]·3H[subscript 2]O (2). Compound 2 has the same lattice structure as 1, but the tricopper unit backbone now traps one ReO[subscript 4]– anion through Coulombic interactions. In addition, three molecules of 2 are bridged by a perrhenate ion, forming a Cu[subscript 3](μ[superscript 3]-ReO[subscript 4]) cluster, to give a different 2-D structure displaying a rare tridentate bridging ReO[subscript 4]– mode. Thus, in addition to classic perrhenate trapping through weak Coulombic interactions, 2 represents an exceptional example in which the ReO[subscript 4]– anion is immobilized in an extended framework through tight covalent interactions. The interlamellar PF[subscript 6]– anions in 1 can be exchanged with other anions including perrhenate, perchlorate, or periodate. The structural similarity between perrhenate and pertechnetate makes these materials of potential interest for pertechnetate trapping

Airway Mucin Concentration as a Marker of Chronic Bronchitis

Chronic obstructive pulmonary disease (COPD) is characterized by chronic bronchitic and emphysematous components. In one biophysical model, the concentration of mucin on the airway surfaces is hypothesized to be a key variable that controls mucus transport in healthy persons versus cessation of transport in persons with muco-obstructive lung diseases. Under this model, it is postulated that a high mucin concentration produces the sputum and disease progression that are characteristic of chronic bronchitis

Progress on improving Agricultural Nitrogen use efficiency: UK-China viortual joint centers on Nitrogen Agronomy

Two virtual joint centers for nitrogen agronomy were established between the UK and China to facilitate collaborative research aimed at improving nitrogen use efficiency (NUE) in agricultural production systems and reducing losses of reactive N to the environment. Major focus areas were improving fertilizer NUE, use of livestock manures, soil health, and policy development and knowledge exchange. Improvements to fertilizer NUE included attention to application rate in the context of yield potential and economic considerations and the potential of improved practices including enhanced efficiency fertilizers, plastic film mulching and cropping design. Improved utilization of livestock manures requires knowledge of the available nutrient content, appropriate manure processing technologies and integrated nutrient management practices. Soil carbon, acidification and biodiversity were considered as important aspects of soil health. Both centers identified a range of potential actions that could be taken to improve N management, and the research conducted has highlighted the importance of developing a systemslevel approach to assessing improvement in the overall efficiency of N management and avoiding unintended secondary effects from individual interventions. Within this context, the management of fertilizer emissions and livestock manure at the farm and regional scales appear to be particularly important targets for mitigation

Magnetic Control of Valley Pseudospin in Monolayer WSe2

Local energy extrema of the bands in momentum space, or valleys, can endow electrons in solids with pseudo-spin in addition to real spin. In transition metal dichalcogenides this valley pseudo-spin, like real spin, is associated with a magnetic moment which underlies the valley-dependent circular dichroism that allows optical generation of valley polarization, intervalley quantum coherence, and the valley Hall effect. However, magnetic manipulation of valley pseudospin via this magnetic moment, analogous to what is possible with real spin, has not been shown before. Here we report observation of the valley Zeeman splitting and magnetic tuning of polarization and coherence of the excitonic valley pseudospin, by performing polarization-resolved magneto-photoluminescence on monolayer WSe2. Our measurements reveal both the atomic orbital and lattice contributions to the valley orbital magnetic moment; demonstrate the deviation of the band edges in the valleys from an exact massive Dirac fermion model; and reveal a striking difference between the magnetic responses of neutral and charged valley excitons which is explained by renormalization of the excitonic spectrum due to strong exchange interactions

A Novel Chromone Derivative with Anti-Inflammatory Property via Inhibition of ROS-Dependent Activation of TRAF6-ASK1-p38 Pathway

The p38 MAPK signaling pathway plays a pivotal role in inflammation. Targeting p38 MAPK may be a potential strategy for the treatment of inflammatory diseases. In the present study, we show that a novel chromone derivative, DCO-6, significantly reduced lipopolysaccharide (LPS)-induced production of nitric oxide, IL-1β and IL-6, decreased the levels of iNOS, IL-1β and IL-6 mRNA expression in both RAW264.7 cells and mouse primary peritoneal macrophages, and inhibited LPS-induced activation of p38 MAPK but not of JNK, ERK. Moreover, DCO-6 specifically inhibited TLR4-dependent p38 activation without directly inhibiting its kinase activity. LPS-induced production of intracellular reactive oxygen species (ROS) was remarkably impaired by DCO-6, which disrupted the formation of the TRAF6-ASK1 complex. Administering DCO-6 significantly protected mice from LPS-induced septic shock in parallel with the inhibition of p38 activation and ROS production. Our results indicate that DCO-6 showed anti-inflammatory properties through inhibition of ROS-dependent activation of TRAF6-ASK1-p38 pathway. Blockade of the upstream events required for p38 MAPK action by DCO-6 may provide a new therapeutic option in the treatment of inflammatory diseases