Implications of an Altered Gut Microbiome in Rat Experimental Vascularized Composite Transplantation.

OBJECTIVES: Vascularized composite allotransplantation is a reconstructive option after severe injury but is fraught with complications, including transplant rejection due to major histocompatibility complex mismatch in the context of allogeneic transplant, which in turn is due to altered immuno-inflammation secondary to transplant. The immunosuppressant tacrolimus can prevent rejection. Because tacrolimus is metabolized predominantly by the gut, this immunosuppressant alters the gut microbiome in multiple ways, thereby possibly affecting immunoinflammation. MATERIALS AND METHODS: We performed either allogeneic or syngeneic transplant with or without tacrolimus in rats. We quantified protein-level inflammatory mediators in the skin, muscle, and plasma and assessed the diversity of the gut microbiome through 16S RNA analysis at several timepoints over 31 days posttransplant. RESULTS: Statistical analysis highlighted a complex interaction between major histocompatibility complex and tacrolimus therapy on the relative diversity of the microbiome. Time-interval principal component analysis indicated numerous significant differences in the tissue characteristics of inflammation and gut microbiome that varied over time and across experimental conditions. Classification and regression tree analysis suggested that both inflammatory mediators in specific tissues and changes in the gut microbiome are useful in characterizing the temporal dynamics of posttransplant inflammation. Dynamic network analysis highlighted unique changes in Methanosphaera that were correlated with Peptococcusin allogeneic transplants with and without tacrolimus versus Prevotella in syngeneic transplant with tacrolimus, suggesting that alterations in Methanosphaera might be a biomarker of vascularized composite allotransplant rejection. CONCLUSIONS: Our results suggest a complex interaction among major histocompatibility complex, local and systemic immuno-inflammation, and tacrolimus therapy and highlight the potential for novel insights into vascularized composite allotransplant from computational approaches.

Unraveling the complex relationship between mRNA and protein abundances: a machine learning-based approach for imputing protein levels from RNA-seq data.

The correlation between messenger RNA (mRNA) and protein abundances has long been debated. RNA sequencing (RNA-seq), a high-throughput, commonly used method for analyzing transcriptional dynamics, leaves questions about whether we can translate RNA-seq-identified gene signatures directly to protein changes. In this study, we utilized a set of 17 widely assessed immune and wound healing mediators in the context of canine volumetric muscle loss to investigate the correlation of mRNA and protein abundances. Our data reveal an overall agreement between mRNA and protein levels on these 17 mediators when examining samples from the same experimental condition (e.g. the same biopsy). However, we observed a lack of correlation between mRNA and protein levels for individual genes under different conditions, underscoring the challenges in converting transcriptional changes into protein changes. To address this discrepancy, we developed a machine learning model to predict protein abundances from RNA-seq data, achieving high accuracy. Our approach also effectively corrected multiple extreme outliers measured by antibody-based protein assays. Additionally, this model has the potential to detect post-translational modification events, as shown by accurately estimating activated transforming growth factor ß1 levels. This study presents a promising approach for converting RNA-seq data into protein abundance and its biological significance.

Dual carbon engineering enabling 1T/2H MoS2 with ultrastable potassium ion storage performance.

Potassium-ion batteries (PIBs) as a promising and low-cost battery technology offer the advantage of utilizing abundant and cost-effective K-salt sources. However, the effective adoption of PIBs necessitates the identification of suitable electrode materials. The 1T phase of MoS2 exhibits enhanced electronic conductivity and greater interlayer spacing compared to the 2H phase, leading to a capable potassium ion storage ability. Herein, we fabricated dual carbon engineered 1T/2H MoS2via a secure and straightforward ammonia-assisted hydrothermal method. The 1T/2H MoS2@rGO@C structure demonstrated an expanded interlayer spacing (9.3 Å). Additionally, the sandwich-like structural design not only enhanced material conductivity but also effectively curbed the agglomeration of nanosheets. Remarkably, 1T/2H MoS2@rGO@C exhibited impressive potassium storage ability, delivering capacities of 351.0 mA h g-1 at 100 mA g-1 and 233.8 mA h g-1 at 1000 mA g-1 following 100 and 1000 cycles, respectively. Moreover, the construction of a K-ion full cell was successfully achieved, utilizing perylene tetracarboxylic dianhydride (PTCDA) as the cathode, and manifesting a capacity of 294.3 mA h g-1 at 100 mA g-1 after 160 cycles. This underscores the substantial potential of employing the 1T/2H MoS2@rGO@C electrode material for PIBs.

A common single nucleotide polymorphism is associated with inflammation and critical illness outcomes.

Acute inflammation is heterogeneous in critical illness and predictive of outcome. We hypothesized that genetic variability in novel, yet common, gene variants contributes to this heterogeneity and could stratify patient outcomes. We searched algorithmically for significant differences in systemic inflammatory mediators associated with any of 551,839 SNPs in one derivation (n = 380 patients with blunt trauma) and two validation (n = 75 trauma and n = 537 non-trauma patients) cohorts. This analysis identified rs10404939 in the LYPD4 gene. Trauma patients homozygous for the A allele (rs10404939AA; 27%) had different trajectories of systemic inflammation along with persistently elevated multiple organ dysfunction (MOD) indices vs. patients homozygous for the G allele (rs10404939GG; 26%). rs10404939AA homozygotes in the trauma validation cohort had elevated MOD indices, and non-trauma patients displayed more complex inflammatory networks and worse 90-day survival compared to rs10404939GG homozygotes. Thus, rs10404939 emerged as a common, broadly prognostic SNP in critical illness.

Tai Ji on Cognitive Function Improvement in Parkinson's Disease: A Meta-Analysis.

BACKGROUND: Tai Ji (TJ) can improve cognitive function, which in turn brings life quality to Parkinson's disease (PD) patients. Cognitive function is thus important for PD patients. Analyzing the cognitive function and obtaining precise TJ exercise prescriptions are effective in treating PD patients. OBJECTIVES: The purpose of this review was to discuss the current Randomized Controlled Trials (RCTs) of TJ and cognitive function improvement in PD. MATERIALS AND METHODS: Databases, including PubMed, Web of Science, Scopus, Cochrane Library, EBSCOhost, Wan Fang, and CNKI, were searched. Cochrane systematic evaluation method was adopted wherein 6 RCTs met the final inclusion criteria. RESULTS: Among the 6 included RCTs, 3 were of high quality, and the rest were of medium quality. Quantitative analysis exhibited that TJ intervention improved the cognitive function of PD patients. TJ promoted the global cognitive function (p < 0.05) and the executive function (p = 0.09) compared with the control. However there was no significant improvement in cognitive motor. TJ training intervention doses of two times a week with 45-60 min sessions over ≤12 weeks could improve the cognitive function of PD patients. CONCLUSIONS: TJ affects the cognitive function of PD patients. However, this effect may have a reduced or no significant impact as the disease increases. PD patients can choose TJ as an intervention for 45-60 min twice a week for at least 12 weeks to accomplish maximum improvement in cognitive function.

Peripheral nerve repair is associated with augmented cross-tissue inflammation following vascularized composite allotransplantation.

Introduction: Vascularized composite allotransplantation (VCA), with nerve repair/coaptation (NR) and tacrolimus (TAC) immunosuppressive therapy, is used to repair devastating traumatic injuries but is often complicated by inflammation spanning multiple tissues. We identified the parallel upregulation of transcriptional pathways involving chemokine signaling, T-cell receptor signaling, Th17, Th1, and Th2 pathways in skin and nerve tissue in complete VCA rejection compared to baseline in 7 human hand transplants and defined increasing complexity of protein-level dynamic networks involving chemokine, Th1, and Th17 pathways as a function of rejection severity in 5 of these patients. We next hypothesized that neural mechanisms may regulate the complex spatiotemporal evolution of rejection-associated inflammation post-VCA. Methods: For mechanistic and ethical reasons, protein-level inflammatory mediators in tissues from Lewis rats (8 per group) receiving either syngeneic (Lewis) or allogeneic (Brown-Norway) orthotopic hind limb transplants in combination with TAC, with and without sciatic NR, were compared to human hand transplant samples using computational methods. Results: In cross-correlation analyses of these mediators, VCA tissues from human hand transplants (which included NR) were most similar to those from rats undergoing VCA + NR. Based on dynamic hypergraph analyses, NR following either syngeneic or allogeneic transplantation in rats was associated with greater trans-compartmental localization of early inflammatory mediators vs. no-NR, and impaired downregulation of mediators including IL-17A at later times. Discussion: Thus, NR, while considered necessary for restoring graft function, may also result in dysregulated and mis-compartmentalized inflammation post-VCA and therefore necessitate mitigation strategies. Our novel computational pipeline may also yield translational, spatiotemporal insights in other contexts.

Hierarchical CoNiO2 Microflowers Assembled by Mesoporous Nanosheets as Efficient Electrocatalysts for Hydrogen Evolution Reaction.

In order to alleviate the energy crisis and propel a low-carbon economy, hydrogen (H2) plays an important role as a renewable cleaning resource. To break the hydrogen evolution reaction (HER) bottleneck, we need high-efficiency electrocatalysts. Based on the synergistic effect between bimetallic oxides, hierarchical mesoporous CoNiO2 nanosheets can be fabricated. Combining physical representations with electrochemical measurements, the resultant CoNiO2 catalysts present the hierarchical microflowers morphology assembled by mesoporous nanosheets. The ultrathin two-dimensional nanosheets and porous surface characteristics provide the vast channels for electrolyte injection, thus endowing CoNiO2 the outstanding HER performance. The excellent performance with a fewer onset potential of 94 mV, a smaller overpotential at 10 mA cm-2, a lower Tafel slope of 109 mV dec-1 and better stability after 1000 cycles makes CoNiO2 better than that of metallic Co and metallic Ni.

A Self-Healing PVA-Linked Phytic Acid Hydrogel-Based Electrolyte for High-Performance Flexible Supercapacitors.

Flexible supercapacitors can be ideal flexible power sources for wearable electronics due to their ultra-high power density and high cycle life. In daily applications, wearable devices will inevitably cause damage or short circuit during bending, stretching, and compression. Therefore, it is necessary to develop proper energy storage devices to meet the requirements of various wearable electronic devices. Herein, Poly(vinyl alcohol) linked various content of phytic acid (PVA-PAx) hydrogels are synthesized with high transparency and high toughness by a one-step freeze-thaw method. The effects of different raw material ratios and agents on the ionic conductivity and mechanical properties of the hydrogel electrolyte are investigated. The PVA-PA21% with 2 M H2SO4 solution (PVA-PA21%-2 M H2SO4) shows a high ionic conductivity of 62.75 mS cm-1. Based on this, flexible supercapacitors fabricated with PVA-PA21%-2 M H2SO4 hydrogel present a high specific capacitance at 1 A g-1 after bending at 90° (64.8 F g-1) and for 30 times (67.3 F g-1), respectively. Moreover, the device shows energy densities of 13.5 Wh kg-1 and 14.0 Wh kg-1 at a power density of 300 W kg-1 after bending at 90° and for 30 times during 10,000 cycles. It provides inspiration for the design and development of electrolytes for related energy electrochemical devices.

Inferring Tissue-Specific, TLR4-Dependent Type 17 Immune Interactions in Experimental Trauma/Hemorrhagic Shock and Resuscitation Using Computational Modeling.

Trauma/hemorrhagic shock followed by resuscitation (T/HS-R) results in multi-system inflammation and organ dysfunction, in part driven by binding of damage-associated molecular pattern molecules to Toll-like Receptor 4 (TLR4). We carried out experimental T/HS-R (pseudo-fracture plus 2 h of shock followed by 0-22 h of resuscitation) in C57BL/6 (wild type [WT]) and TLR4-null (TLR4-/-) mice, and then defined the dynamics of 20 protein-level inflammatory mediators in the heart, gut, lung, liver, spleen, kidney, and systemic circulation. Cross-correlation and Principal Component Analysis (PCA) on data from the 7 tissues sampled suggested that TLR4-/- samples express multiple inflammatory mediators in a small subset of tissue compartments as compared to the WT samples, in which many inflammatory mediators were localized non-specifically to nearly all compartments. We and others have previously defined a central role for type 17 immune cells in human trauma. Accordingly, correlations between IL-17A and GM-CSF (indicative of pathogenic Th17 cells); between IL-17A and IL-10 (indicative of non-pathogenic Th17 cells); and IL-17A and TNF (indicative of memory/effector T cells) were assessed across all tissues studied. In both WT and TLR4-/- mice, positive correlations were observed between IL-17A and GM-CSF, IL-10, and TNF in the kidney and gut. In contrast, the variable and dynamic presence of both pathogenic and non-pathogenic Th17 cells was inferred in the systemic circulation of TLR4-/- mice over time, suggesting a role for TLR4 in efflux of these cells into peripheral tissues. Hypergraph analysis - used to define dynamic, cross compartment networks - in concert with PCA-suggested that IL-17A was present persistently in all tissues at all sampled time points except for its absence in the plasma at 0.5h in the WT group, supporting the hypothesis that T/HS-R induces efflux of Th17 cells from the circulation and into specific tissues. These analyses suggest a complex, context-specific role for TLR4 and type 17 immunity following T/HS-R.

Research on Optimization of Process Parameters of Traditional Chinese Medicine Based on Data Mining Technology.

Data mining technology and methods are used to effectively optimize manufacturing process parameters due to the complexity and uniqueness of the process parameters. The data-mining-based optimization method for traditional Chinese medicine (TCM) process parameters is presented, along with a list of process parameters that have shown to be effective in actual production. The influencing factors of process parameters are analyzed and modeled using an attribute weight analysis and classification analysis algorithm. The optimization scheme of process parameters that meet the requirements is selected, and an example is given for verification, by selecting data records that fall within a certain error range and incorporating the rules of association knowledge discovery. The support vector classification algorithm has a higher accuracy, despite the algorithm's results being understandable. The support vector regression algorithm developed a reliable process optimization model.

A putative "chemokine switch" that regulates systemic acute inflammation in humans.

Systemic inflammation is complex and likely drives clinical outcomes in critical illness such as that which ensues following severe injury. We obtained time course data on multiple inflammatory mediators in the blood of blunt trauma patients. Using dynamic network analyses, we inferred a novel control architecture for systemic inflammation: a three-way switch comprising the chemokines MCP-1/CCL2, MIG/CXCL9, and IP-10/CXCL10. To test this hypothesis, we created a logical model comprising this putative architecture. This model predicted key qualitative features of systemic inflammation in patient sub-groups, as well as the different patterns of hospital discharge of moderately vs. severely injured patients. Thus, a rational transition from data to data-driven models to mechanistic models suggests a novel, chemokine-based mechanism for control of acute inflammation in humans and points to the potential utility of this workflow in defining novel features in other complex diseases.

The Effects of Tacrolimus on Tissue-Specific, Protein-Level Inflammatory Networks in Vascularized Composite Allotransplantation.

Systems-level insights into inflammatory events after vascularized composite allotransplantation (VCA) are critical to the success of immunomodulatory strategies of these complex procedures. To date, the effects of tacrolimus (TAC) immunosuppression on inflammatory networks in VCA, such as in acute rejection (AR), have not been investigated. We used a systems biology approach to elucidate the effects of tacrolimus on dynamic networks and principal drivers of systemic inflammation in the context of dynamic tissue-specific immune responses following VCA. Lewis (LEW) rat recipients received orthotopic hind limb VCA from fully major histocompatibility complex-mismatched Brown Norway (BN) donors or matched LEW donors. Group 1 (syngeneic controls) received LEW limbs without TAC, and Group 2 (treatment group) received BN limbs with TAC. Time-dependent changes in 27 inflammatory mediators were analyzed in skin, muscle, and peripheral blood using Principal Component Analysis (PCA), Dynamic Bayesian Network (DyBN) inference, and Dynamic Network Analysis (DyNA) to define principal characteristics, central nodes, and putative feedback structures of systemic inflammation. Analyses were repeated on skin + muscle data to construct a "Virtual VCA", and in skin + muscle + peripheral blood data to construct a "Virtual Animal." PCA, DyBN, and DyNA results from individual tissues suggested important roles for leptin, VEGF, various chemokines, the NLRP3 inflammasome (IL-1ß, IL-18), and IL-6 after TAC treatment. The chemokines MCP-1, MIP-1α; and IP-10 were associated with AR in controls. Statistical analysis suggested that 24/27 inflammatory mediators were altered significantly between control and TAC-treated rats in peripheral blood, skin, and/or muscle over time. "Virtual VCA" and "Virtual Animal" analyses implicated the skin as a key control point of dynamic inflammatory networks, whose connectivity/complexity over time exhibited a U-shaped trajectory and was mirrored in the systemic circulation. Our study defines the effects of TAC on complex spatiotemporal evolution of dynamic inflammation networks in VCA. We also demonstrate the potential utility of computational analyses to elucidate nonlinear, cross-tissue interactions. These approaches may help define precision medicine approaches to better personalize TAC immunosuppression in VCA recipients.

Inflammatory signals and network connections implicate cell-mediated immunity in chronic venous insufficiency.

BACKGROUND: The role of inflammation in superficial venous reflux in varicose veins (VVs) is unknown. Computational network modeling has deduced inflammation in experimental and clinical settings. We measured immune mediators in plasma from competent and incompetent leg veins inferring the role of cellular immunity based on cytokine networks. METHODS: Temperature was assessed using infrared thermography (IRT) to measure inflammation. Blood was obtained during sclerotherapy or endovenous thermal ablation for VVs. Control subjects underwent phlebotomy from saphenous and forearm veins. Vein segments were harvested during surgery. Demographics, clinical, etiology, anatomy and pathophysiology classification, venous clinical severity scores (VCSSs), and body mass index (BMI) were collected. Twenty-five mediators were measured in serum and vein segments. Means were compared using Mann-Whitney U test. Pearson correlations equaling or exceeding a threshold prompted connections among nodes, and mapped as networks. Spearman correlations were performed between interleukin (IL)-17A and both granulocyte macrophage colony stimulation factor, and IL-10 as indicators of pathogenic and nonpathogenic Th17 cell involvement. RESULTS: Age, BMI, and VCSSs differed significantly between groups. Temperatures were higher over diseased veins. Plasma concentrations of 20 cytokines differed between control and patient subjects (P<0.05), and most were lower in patients. C-X-C motif chemokine ligand-9 (aka monokine-induced by gamma interferon), C-X-C motif chemokine ligand 10 (aka IFNγ induced protein 10), and soluble IL-2 receptor-alpha were higher in patients, but not connected to other mediators in networks. In contrast, IL-17A, IL-12p70, and interferon gamma were the only mediators that were more highly interconnected in venous insufficiency. IL-17A and granulocyte macrophage colony stimulating factor (GM-CSF) were highly correlated in chronic venous insufficiency (CVI) but not in controls. In tissue, refluxing VVs significantly higher IL-15 expression than competent saphenous veins. CONCLUSIONS: Venous insufficiency associates with age, BMI, skin temperature, and plasma cytokines associated with interferon gamma and possibly IL-17A signaling. The vein wall may be a source of activation of cellular activation, given elevated IL-15 expression. Correlations between IL-17A and GM-CSF suggested a potential role for pathogenic Th17 cells in VVs. Differentially expressed inflammatory networks induced by venous hypertension may reflect or drive venous damage and ulceration.

Aqueous Calcium-Ion Battery Based on a Mesoporous Organic Anode and a Manganite Cathode with Long Cycling Performance.

Aqueous batteries have attracted increasing and extensive attention, owing to their high safety, low cost, and low toxicity. These factors have become increasingly important, given the current focus on the rapid development of green energy technologies. In particular, multivalent-ion batteries are emerging as alternatives to lithium-ion batteries. Unfortunately, magnesium and aluminum ions have high polarization strengths that are unfavorable for electrode materials. In contrast, calcium-ion batteries successfully avoid the problem of high polarization. Herein, an aqueous calcium-ion battery (CIBs) based on mesoporous silica SBA-15 with a two-dimensional hexagonal through-hole structure is reported. The poly(3,4,9,10-perylentetracarboxylic diimide) (PPTCDI) organic material supported on SBA-15 is used as the anode and displays a capacity of 201 mAh g-1 , with a stable cycling performance of 95 % capacity retention after 1500 cycles. SBA-15@PPTCDI‖Ca2 MnO4 aqueous CIBs demonstrate a high energy density of 130.6 Wh kg-1 in the cell voltage range from 0.0 to 1.8 V, with a high capacity and excellent cycling stability. As the anode material, SBA-15@PPTCDI shows special bonding of redox electrons that leads to its highly stable performance, which paves the way for addressing the shortcomings of traditional organic electrode materials. The localization and delocalization of the redox electron offers additional voltage stability, which is another important advantage for practical applications. This study highlights the potential of organic electrode materials for applications in aqueous multivalent-metal-ion batteries.

Efficient bifunctional catalysts synthesized from three-dimensional Ni/Fe bimetallic organic frameworks for overall urea electrolysis.

Herein, a three-dimensional (3D) Ni/Fe bimetallic organic framework (MOF-Ni@MOF-Fe) with a structure of rhombus blocks on nanosheets is synthesized on Ni foam by a 2-step solvothermal method. After sulfide reaction, MOF-Ni@MOF-Fe-S is vulcanized by MOF-Ni@MOF-Fe with a structure of interwoven and folding nanosheets. Meanwhile, Ni3S2 is formed under the influence of iron. This special structure makes MOF-Ni@MOF-Fe-S to expose more active sites. MOF-Ni@MOF-Fe-S shows superior urea oxidation reaction (UOR) and hydrogen evolution reaction (HER) performance. When MOF-Ni@MOF-Fe-S is used as UOR and HER catalysts, it has low potentials of 1.347 V (vs. RHE) at 10 mA cm-2 and 0.145 V (vs. RHE) at 10 mA cm-2 in 1.0 M KOH with 0.5 M urea, respectively. MOF-Ni@MOF-Fe-S as a bifunctional electrode is assembled as an alkaline urea electrolyzer, showing catalytic activity at a low cell voltage of 1.539 V at 10 mA cm-2 and excellent stability during 10 h chronopotentiometry analysis.

Prehospital plasma is associated with distinct biomarker expression following injury.

BACKGROUNDPrehospital plasma improves survival in severely injured patients transported by air ambulance. We hypothesized that prehospital plasma would be associated with a reduction in immune imbalance and endothelial damage.METHODSWe sampled blood from 405 trauma patients enrolled in the Prehospital Air Medical Plasma (PAMPer) trial upon hospital admission (0 hours) and 24 hours post admission across 6 U.S. sites. We assayed samples for 21 inflammatory mediators and 7 markers associated with endothelial function and damage. We performed hierarchical clustering analysis (HCA) of these biomarkers of the immune response and endothelial injury. Regression analysis was used to control for differences across study and to assess any association with prehospital plasma resuscitation.RESULTSHCA distinguished two patient clusters with different injury patterns and outcomes. Patients in cluster A had greater injury severity and incidence of blunt trauma, traumatic brain injury, and mortality. Cluster A patients that received prehospital plasma showed improved 30-day survival. Prehospital plasma did not improve survival in cluster B patients. In an adjusted analysis of the most seriously injured patients, prehospital plasma was associated with an increase in adiponectin, IL-1ß, IL-17A, IL-23, and IL-17E upon admission, and a reduction in syndecan-1, TM, VEGF, IL-6, IP-10, MCP-1, and TNF-α, and an increase in IL-33, IL-21, IL-23, and IL-17E 24 hours later.CONCLUSIONPrehospital plasma may ameliorate immune dysfunction and the endotheliopathy of trauma. These effects of plasma may contribute to improved survival in injured patients.TRIAL REGISTRATIONNCT01818427.FUNDINGDepartment of Defense; National Institutes of Health, U.S. Army.

MXene-Derived Defect-Rich TiO2@rGO as High-Rate Anodes for Full Na Ion Batteries and Capacitors.

Sodium ion batteries and capacitors have demonstrated their potential applications for next-generation low-cost energy storage devices. These devices's rate ability is determined by the fast sodium ion storage behavior in electrode materials. Herein, a defective TiO2@reduced graphene oxide (M-TiO2@rGO) self-supporting foam electrode is constructed via a facile MXene decomposition and graphene oxide self-assembling process. The employment of the MXene parent phase exhibits distinctive advantages, enabling defect engineering, nanoengineering, and fluorine-doped metal oxides. As a result, the M-TiO2@rGO electrode shows a pseudocapacitance-dominated hybrid sodium storage mechanism. The pseudocapacitance-dominated process leads to high capacity, remarkable rate ability, and superior cycling performance. Significantly, an M-TiO2@rGO//Na3V2(PO4)3 sodium full cell and an M-TiO2@rGO//HPAC sodium ion capacitor are fabricated to demonstrate the promising application of M-TiO2@rGO. The sodium ion battery presents a capacity of 177.1 mAh g-1 at 500 mA g-1 and capacity retention of 74% after 200 cycles. The sodium ion capacitor delivers a maximum energy density of 101.2 Wh kg-1 and a maximum power density of 10,103.7 W kg-1. At 1.0 A g-1, it displays an energy retention of 84.7% after 10,000 cycles.

Dynamics of Systemic Inflammation as a Function of Developmental Stage in Pediatric Acute Liver Failure.

The Pediatric Acute Liver Failure (PALF) study is a multicenter, observational cohort study of infants and children diagnosed with this complex clinical syndrome. Outcomes in PALF reflect interactions among the child's clinical condition, response to supportive care, disease severity, potential for recovery, and, if needed, availability of a suitable organ for liver transplantation (LTx). Previously, we used computational analyses of immune/inflammatory mediators that identified three distinct dynamic network patterns of systemic inflammation in PALF associated with spontaneous survivors, non-survivors (NS), and LTx recipients. To date, there are no data exploring age-specific immune/inflammatory responses in PALF. Accordingly, we measured a number of clinical characteristics and PALF-associated systemic inflammatory mediators in daily serum samples collected over the first 7 days following enrollment from five distinct PALF cohorts (all spontaneous survivors without LTx): infants (INF, <1 year), toddlers (TOD, 1-2 years.), young children (YCH, 2-4 years), older children (OCH, 4-13 years) and adolescents (ADO, 13-18 years). Among those groups, we observed significant (P<0.05) differences in ALT, creatinine, Eotaxin, IFN-γ, IL-1RA, IL-1ß, IL-2, sIL-2Rα, IL-4, IL-6, IL-12p40, IL-12p70, IL-13, IL-15, MCP-1, MIP-1α, MIP-1ß, TNF-α, and NO2-/NO3- . Dynamic Bayesian Network inference identified a common network motif with HMGB1 as a central node in all sub-groups, with MIG/CXCL9 being a central node in all groups except INF. Dynamic Network Analysis (DyNA) inferred different dynamic patterns and overall dynamic inflammatory network complexity as follows: OCH>INF>TOD>ADO>YCH. Hypothesizing that systemically elevated but sparsely connected inflammatory mediators represent pathological inflammation, we calculated the AuCon score (area under the curve derived from multiple measures over time divided by DyNA connectivity) for each mediator, and identified HMGB1, MIG, IP-10/CXCl10, sIL-2Rα, and MCP-1/CCL2 as potential correlates of PALF pathophysiology, largely in agreement with the results of Partial Least Squares Discriminant Analysis. Since NS were in the INF age group, we compared NS to INF and found greater inflammatory coordination and dynamic network connectivity in NS vs. INF. HMGB1 was the sole central node in both INF and NS, though NS had more downstream nodes. Thus, multiple machine learning approaches were used to gain both basic and potentially translational insights into a complex inflammatory disease.

Computational Derivation of Core, Dynamic Human Blunt Trauma Inflammatory Endotypes.

Systemic inflammation ensues following traumatic injury, driving immune dysregulation and multiple organ dysfunction (MOD). While a balanced immune/inflammatory response is ideal for promoting tissue regeneration, most trauma patients exhibit variable and either overly exuberant or overly damped responses that likely drive adverse clinical outcomes. We hypothesized that these inflammatory phenotypes occur in the context of severe injury, and therefore sought to define clinically distinct endotypes of trauma patients based on their systemic inflammatory responses. Using Patient-Specific Principal Component Analysis followed by unsupervised hierarchical clustering of circulating inflammatory mediators obtained in the first 24 h after injury, we segregated a cohort of 227 blunt trauma survivors into three core endotypes exhibiting significant differences in requirement for mechanical ventilation, duration of ventilation, and MOD over 7 days. Nine non-survivors co-segregated with survivors. Dynamic network inference, Fisher Score analysis, and correlations of IL-17A with GM-CSF, IL-10, and IL-22 in the three survivor sub-groups suggested a role for type 3 immunity, in part regulated by Th17 and γδ 17 cells, and related tissue-protective cytokines as a key feature of systemic inflammation following injury. These endotypes may represent archetypal adaptive, over-exuberant, and overly damped inflammatory responses.

An Aging-Related Single-Nucleotide Polymorphism is Associated With Altered Clinical Outcomes and Distinct Inflammatory Profiles in Aged Blunt Trauma Patients.

The contribution of individual genetic determinants of aging to the adverse clinical outcomes and altered inflammation mediator networks characteristic of aged trauma patients is unknown. The AA genotype of the aging-related single-nucleotide polymorphism (SNP) rs2075650 in TOMM40 has been associated with longevity, while the AG and GG genotypes are associated with an increased risk of Alzheimer disease. Here, we studied the effect of rs2075650 on clinical outcomes and dynamic biomarker patterns after traumatic injury. Genomic DNA was obtained from blunt trauma patients admitted to the ICU and examined for 551,839 SNPs using an Illumina microarray kit. Plasma was sampled from each patient three times within the first 24 h and daily from day 1 to 7 then assayed for 31 biomarkers using Luminex. Aged patients (65-90 years) were segregated into AA (n = 77) and AG/GG (n = 17) genotypes. Additional comparisons were made with matched groups of young patients (18-30 years), controlling for injury severity score (ISS) and sex ratio, and also segregated into AA (n = 56) and AG/GG (n = 19) genotypes. Aged patients with the AA genotype had a significantly lower requirement for ventilation and fewer days on mechanical ventilation, as well as significantly higher levels of one mediator and lower levels of two mediators. Dynamic Bayesian Network inference revealed IL-23 as a central node in each network regardless of age or genotype, with MIG and IP-10 also as key mediators in the networks of the aged patients. These findings suggest that an aging-related SNP, rs2075650, may influence clinical outcomes and inflammation networks in aged patients following blunt trauma, and thus may serve as a predictive outcome biomarker in the setting of polytrauma.