An organotrisulfide (RSSSR, R is an organic group) has three sulfur atoms which could be involved in multi-electron reduction reactions; therefore it is a promising electrode material for batteries. Herein, we use dimethyl trisulfide (DMTS) as a model compound to study its redox reactions in rechargeable lithium batteries. With the aid of XRD, XPS, and GC-MS analysis, we confirm DMTS could undergo almost a 4 e(-) reduction process in a complete discharge to 1.0 V. The discharge products are primarily LiSCH3 and Li2 S. The lithium cell with DMTS catholyte delivers an initial specific capacity of 720 mAh g(-1) DMTS and retains 82 % of the capacity over 50 cycles at C/10 rate. When the electrolyte/DMTS ratio is 3:1 mL g(-1) , the reversible specific energy for the cell including electrolyte can be 229 Wh kg(-1) . This study shows organotrisulfide is a promising high-capacity cathode material for high-energy rechargeable lithium batteries.

Bidirectional cell-cell communication involving exosome-borne cargo such as miRNA, has emerged as a critical mechanism for wound healing. Unlike other shedding vesicles, exosomes selectively package miRNA by SUMOylation of heterogeneous nuclear ribonucleoproteinA2B1 (hnRNPA2B1). In this work, we elucidate the significance of exosome in keratinocyte-macrophage crosstalk following injury. Keratinocyte-derived exosomes were genetically labeled with GFP reporter (Exo κ-GFP ) using tissue nanotransfection and were isolated from dorsal murine skin and wound-edge tissue by affinity selection using magnetic beads. Surface N-glycans of Exo κ-GFP were also characterized. Unlike skin exosome, wound-edge Exo κ-GFP demonstrated characteristic N-glycan ions with abundance of low base pair RNA and were selectively engulfed by woundmacrophages (ωmϕ) in granulation tissue. In vitro addition of wound-edge Exo κ-GFP to proinflammatory ωmϕ resulted in conversion to a proresolution phenotype. To selectively inhibit miRNA packaging within Exo κ-GFP in vivo, pH-responsive keratinocyte-targeted siRNA-hnRNPA2B1 functionalized lipid nanoparticles (TLNP κ ) were designed with 94.3% encapsulation *

Organotrisulfide (RSSSR) is a new class of high-capacity cathode materials for rechargeable lithium batteries. The organic R group can tune the structure and property of organotrisulfide as well as electrochemical performance in batteries. Herein, a nominal diphenyl trisulfide (DPTS, C6H5SSSC6H5) catholyte is reported for rechargeable lithium batteries. Three sulfur atoms allow 4e– storage per molecule, affording DPTS with a theoretical capacity of 428 mAh g–1. The DPTS catholyte is synthesized from a coupling reaction of diphenyl disulfide (DPDS) and elemental sulfur in liquid electrolyte at 70 °C. It is found that the DPTS catholyte is a mixture of DPTS, DPDS, and elemental sulfur in the electrolyte. The lithium cell with the DPTS catholyte delivers an initial specific capacity of 330 mAh g–1 DPTS and retains 79% of the initial capacity over 100 cycles at the C/2 rate. The cell delivers an initial discharge specific energy of 751 Wh kg–1 DPTS with a high energy efficiency of over 95% at the C/5 rate. The achievable energy density of the DPTS catholyte (1.0 M) is 158 Wh L–1. This study shows that DPTS is a promising high-capacity cathode material for highly reversible lithium batteries.

Diabetes is a disease that involves dysregulation of metabolic processes. Patients with type 1 diabetes (T1D) require insulin injections and measured food intake to maintain clinical stability, manually tracking their results by measuring blood glucose levels. Low blood glucose levels, hypoglycemia, can be extremely dangerous and can result in seizures, coma, or even death. Canines trained as diabetes alert dogs (DADs) have demonstrated the ability to detect hypoglycemia from breath, which led us to hypothesize that hypoglycemia, a metabolic dysregulation leading to low blood glucose levels, could be identified through analyzing volatile organic compounds (VOCs) contained within breath. We hoped to replicate the canines' detection ability and success by analytically using gas chromatography/mass spectrometry of VOCs in 128 breath samples collected from 52 youths with T1D at two different diabetes camps. We used different tests for significance including Ranksum, Student's T-test, and difference between means, and found a subset of 56 traces of potential metabolites. Principle component and linear discriminant analysis (LDA) confirmed a hypoglycemic signature likely resides within this group. Supervised machine learning combined with LDA narrowed the list of likely components to seven. The technique of leave one out cross validation demonstrated the model thus developed has a sensitivity of 91% (95% confidence interval (CI) [57.1, 94.7]) and a specificity of 84% (95% CI [73.0, 92.7]) at identifying hypoglycemia. Confidence intervals were obtained by bootstrapping. These results demonstrate that it is possible to differentiate breath samples obtained during hypoglycemic events from all other breath samples by analytical means and could lead to developing a simple analytical monitoring device as an alternative to using DADs.

Distinct lipid environments, including lipid rafts, are increasingly recognized as a crucial factor affecting membrane protein function in plasma membranes. Unfortunately, an understanding of their role in membrane protein activation and oligomerization has remained elusive due to the challenge of characterizing these often small and transient plasma membrane heterogeneities in live cells. To address this difficulty, we present an experimental model membrane platform based on polymer-supported lipid bilayers containing stable raft-mimicking domains (type I) and homogeneous cholesterol-lipid mixtures (type II) into which transmembrane proteins are incorporated (α(v)β(3) and α(5)β(1) integrins). These flexible lipid platforms enable the use of confocal fluorescence spectroscopy, including the photon counting histogram method, in tandem with epifluorescence microscopy to quantitatively probe the effect of the binding of native ligands from the extracellular matrix ligands (vitronectin and fibronectin for α(v)β(3) and α(5)β(1), respectively) on domain-specific protein sequestration and on protein oligomerization state. We found that both α(v)β(3) and α(5)β(1) sequester preferentially to nonraft domains in the absence of extracellular matrix ligands, but upon ligand addition, α(v)β(3) sequesters strongly into raft-like domains and α(5)β(1) loses preference for either raft-like or nonraft-like domains. A corresponding photon counting histogram analysis showed that integrins exist predominantly in a monomeric state. No change was detected in oligomerization state upon ligand binding in either type I or type II bilayers, but a moderate increase in oligomerization state was observed for increasing concentrations of cholesterol. The combined findings suggest a mechanism in which changes in integrin sequestering are caused by ligand-induced changes in integrin conformation and/or dynamics that affect integrin-lipid interactions without altering the integrin oligomerization state.

Breast cancer is the most common cancer detected in women and current screening methods for the disease are not sensitive. Volatile organic compounds (VOCs) include endogenous metabolites that provide information about health and disease which might be useful to develop a better screening method for breast cancer. The goal of this study was to classify mice with and without tumors and compare tumors localized to the mammary pad and tumor cells injected into the iliac artery by differences in VOCs in urine. After 4T1.2 tumor cells were injected into BALB/c mice either in the mammary pad or into the iliac artery, urine was collected, VOCs from urine headspace were concentrated by solid phase microextraction and results were analyzed by gas chromatography-mass spectrometry quadrupole time-of-flight. Multivariate and univariate statistical analyses were employed to find potential biomarkers for breast cancer and metastatic breast cancer in mice models. A set of six VOCs classified mice with and without tumors with an area under the receiver operator characteristic (ROC AUC) of 0.98 (95% confidence interval [0.85, 1.00]) via five-fold cross validation. Classification of mice with tumors in the mammary pad and iliac artery was executed utilizing a different set of six VOCs, with a ROC AUC of 0.96 (95% confidence interval [0.75, 1.00]).

Osteocytes are mechanosensitive bone cells, but little is known about their effects on tumor cells in response to mechanical stimulation. We treated breast cancer cells with osteocyte-derived conditioned medium (CM) and fluid flow-treated conditioned medium (FFCM) with 0.25 Pa and 1 Pa shear stress. Notably, CM and FFCM at 0.25 Pa induced the mesenchymal-to-epithelial transition (MET), but FFCM at 1 Pa induced the epithelial-to-mesenchymal transition (EMT). This suggested that the effects of fluid flow on conditioned media depend on flow intensity. Fluorescence resonance energy transfer (FRET)-based evaluation of Src activity and vinculin molecular force showed that osteopontin was involved in EMT and MET switching. A mouse model of tumorinduced osteolysis was tested using dynamic tibia loadings of 1, 2, and 5 N. The low 1 N loading suppressed tumor-induced osteolysis, but this beneficial effect was lost and reversed with loads at 2 and 5 N, respectively. Changing the loading intensities in vivo also led to changes in serum TGFβ levels and the composition of tumor-associated volatile organic compounds in the urine. Collectively, this study demonstrated the critical role of intensity-dependent mechanotransduction and osteopontin in tumorosteocyte communication, indicating that a biophysical factor can tangibly alter the behaviors of tumor cells in the bone microenvironment.

There is growing recognition that lipid heterogeneities in cellular membranes play an important role in the distribution and functionality of membrane proteins. However, the detection and characterization of such heterogeneities at the cellular level remains challenging. Here we report on the poorly understood relationship between lipid bilayer asymmetry and membrane protein sequestering in raft-mimicking model membrane mixtures using a powerful experimental platform comprised of confocal spectroscopy XY-scan and photon-counting histogram analyses. This experimental approach is utilized to probe the domain-specific sequestering and oligomerization state of αvβ3 and α5β1 integrins in bilayers, which contain coexisting liquid-disordered/liquid-ordered (ld/lo) phase regions exclusively in the top leaflet of the bilayer (bottom leaflet contains ld phase). Comparison with previously reported integrin sequestering data in bilayer-spanning lo-ld phase separations demonstrates that bilayer asymmetry has a profound influence on αvβ3 and α5β1 sequestering behavior. For example, both integrins sequester preferentially to the lo phase in asymmetric bilayers, but to the ld phase in their symmetric counterparts. Furthermore, our data show that bilayer asymmetry significantly influences the role of native ligands in integrin sequestering.