Publications by authors named "John Li"

157 Publications

High-Resolution Laser-Induced Graphene from Photoresist.

ACS Nano 2021 Apr 26. Epub 2021 Apr 26.

Department of Materials Sciences, The University of Tennessee, Knoxville, Tennessee 37996, United States.

The fabrication of patterned graphene electronics at high resolution is an important challenge for many applications in microelectronics. Here, we demonstrate the conversion of positive photoresist (PR), commonly employed in the commercial manufacture of consumer electronics, into laser-induced graphene (LIG). Sequential lasing converts the PR photopolymer first into amorphous carbon, then to photoresist-derived LIG (PR-LIG). The resulting material possesses good conductivity and is easily doped with metal or other additives for additional functionality. Furthermore, photolithographic exposure of PR prior to lasing enables the generation of PR-LIG patterns small enough to be invisible to the naked eye. By exploiting PR as a photopatternable LIG precursor, PR-LIG can be synthesized with a spatial resolution of ∼10 μm, up to 15 times smaller than conventional LIG patterning methods. The patterning of these small PR-LIG features could offer a powerful and broadly accessible strategy for the fabrication of microscale LIG-derived nanocomposites for on-chip devices.
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http://dx.doi.org/10.1021/acsnano.1c01843DOI Listing
April 2021

AMPK-dependent and -independent coordination of mitochondrial function and muscle fiber type by FNIP1.

PLoS Genet 2021 Mar 29;17(3):e1009488. Epub 2021 Mar 29.

MOE Key Laboratory of Model Animals for Disease Study, Department of Spine Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Chemistry and Biomedicine Innovation Center (ChemBIC), Model Animal Research Center, Nanjing University Medical School, Nanjing University, Nanjing, China.

Mitochondria are essential for maintaining skeletal muscle metabolic homeostasis during adaptive response to a myriad of physiologic or pathophysiological stresses. The mechanisms by which mitochondrial function and contractile fiber type are concordantly regulated to ensure muscle function remain poorly understood. Evidence is emerging that the Folliculin interacting protein 1 (Fnip1) is involved in skeletal muscle fiber type specification, function, and disease. In this study, Fnip1 was specifically expressed in skeletal muscle in Fnip1-transgenic (Fnip1Tg) mice. Fnip1Tg mice were crossed with Fnip1-knockout (Fnip1KO) mice to generate Fnip1TgKO mice expressing Fnip1 only in skeletal muscle but not in other tissues. Our results indicate that, in addition to the known role in type I fiber program, FNIP1 exerts control upon muscle mitochondrial oxidative program through AMPK signaling. Indeed, basal levels of FNIP1 are sufficient to inhibit AMPK but not mTORC1 activity in skeletal muscle cells. Gain-of-function and loss-of-function strategies in mice, together with assessment of primary muscle cells, demonstrated that skeletal muscle mitochondrial program is suppressed via the inhibitory actions of FNIP1 on AMPK. Surprisingly, the FNIP1 actions on type I fiber program is independent of AMPK and its downstream PGC-1α. These studies provide a vital framework for understanding the intrinsic role of FNIP1 as a crucial factor in the concerted regulation of mitochondrial function and muscle fiber type that determine muscle fitness.
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http://dx.doi.org/10.1371/journal.pgen.1009488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8031738PMC
March 2021

Millisecond Conversion of Metastable 2D Materials by Flash Joule Heating.

ACS Nano 2021 Jan 7;15(1):1282-1290. Epub 2021 Jan 7.

Controllable phase engineering is vital for precisely tailoring material properties since different phase structures have various electronic states and atomic arrangements. Rapid synthesis of thermodynamically metastable materials, especially two-dimensional metastable materials, with high efficiency and low cost remains a large challenge. Here we report flash Joule heating (FJH) as an electrothermal method to achieve the bulk conversion of transition metal dichalcogenides, MoS and WS, from 2H phases to 1T phases in milliseconds. The conversions can reach up to 76% of flash MoS using tungsten powder as conductive additive. Different degrees of phase conversion can be realized by controlling the FJH conditions, such as reaction duration and additives, which allows the study of ratio-dependent properties. First-principles calculations confirm that structural processes associated with the FJH, such as vacancy formation and charge accumulation, result in stabilization of the 1T phases. FJH offers rapid access to bulk quantities of the hitherto hard-to-access 1T phases, a promising method for further fundamental research and diverse applications of metastable phases.
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http://dx.doi.org/10.1021/acsnano.0c08460DOI Listing
January 2021

Mesenchymal VEGFA induces aberrant differentiation in heterotopic ossification.

Bone Res 2019 Dec 10;7(1):36. Epub 2019 Dec 10.

Department of Surgery, University of Michigan, Ann Arbor, MI, 48109, USA.

Heterotopic ossification (HO) is a debilitating condition characterized by the pathologic formation of ectopic bone. HO occurs commonly following orthopedic surgeries, burns, and neurologic injuries. While surgical excision may provide palliation, the procedure is often burdened with significant intra-operative blood loss due to a more robust contribution of blood supply to the pathologic bone than to native bone. Based on these clinical observations, we set out to examine the role of vascular signaling in HO. Vascular endothelial growth factor A (VEGFA) has previously been shown to be a crucial pro-angiogenic and pro-osteogenic cue during normal bone development and homeostasis. Our findings, using a validated mouse model of HO, demonstrate that HO lesions are highly vascular, and that VEGFA is critical to ectopic bone formation, despite lacking a contribution of endothelial cells within the developing anlagen.
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http://dx.doi.org/10.1038/s41413-019-0075-6DOI Listing
December 2019

Nanocars with Permanent Dipoles: Preparing for the Second International Nanocar Race.

J Org Chem 2020 11 21;85(21):13644-13654. Epub 2020 Oct 21.

Department of Physical and Applied Sciences, University of Houston-Clear Lake, 2700 Bay Area Boulevard, Houston, Texas 77058, United States.

With the desire to synthesize surface-rolling molecular machines that can be translated and rotated with extreme precision and speed, we have synthesized a series of five nanocars. Each structure features a permanent dipole moment, generated by an ,-dimethylamino- moiety on one end of the car coupled with a nitro group on the other end. These cars are designed to be stimulated with an electric field gradient from a scanning probe microscopy tip. The nanocars all possess unexplored combinations of structural features: -butyl wheels, short alkyne chassis, and combination sets of wheels including one set of -butyl wheels and another set of larger adamantane wheels on the same car. Each of these features needs to be assessed as preparation for the second International Nanocar Race that is taking place in 2022.
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http://dx.doi.org/10.1021/acs.joc.0c01811DOI Listing
November 2020

IRF4 in Skeletal Muscle Regulates Exercise Capacity via PTG/Glycogen Pathway.

Adv Sci (Weinh) 2020 Oct 1;7(19):2001502. Epub 2020 Aug 1.

Division of Pediatric Endocrinology Department of Pediatrics UCLA Children's Discovery and Innovation Institute David Geffen School of Medicine at UCLA Los Angeles CA 90095 USA.

Exercise-induced fatigue and exhaustion are interesting areas for many researchers. Muscle glycogen is critical for physical performance. However, how glycogen metabolism is manipulated during exercise is not very clear. The aim here is to assess the impact of interferon regulatory factor 4 (IRF4) on skeletal muscle glycogen and subsequent regulation of exercise capacity. Skeletal muscle-specific IRF4 knockout mice show normal body weight and insulin sensitivity, but better exercise capacity and increased glycogen content with unaltered triglyceride levels compared to control mice on chow diet. In contrast, mice overexpression of IRF4 displays decreased exercise capacity and lower glycogen content. Mechanistically, IRF4 regulates glycogen-associated regulatory subunit protein targeting to glycogen (PTG) to manipulate glucose metabolism in skeletal muscle. Knockdown of PTG can reverse the effects imposed by the absence of IRF4 in vivo. These studies reveal a regulatory pathway including IRF4/PTG/glycogen synthesis on controlling exercise capacity.
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http://dx.doi.org/10.1002/advs.202001502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539189PMC
October 2020

Cold-Inducible Klf9 Regulates Thermogenesis of Brown and Beige Fat.

Diabetes 2020 12 29;69(12):2603-2618. Epub 2020 Sep 29.

Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Key Laboratory of Cellular Homeostasis and Disease, Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, China

Promoting development and function of brown and beige fat may represent an attractive treatment of obesity. In the current study, we show that fat expression is markedly induced by cold exposure and a β-adrenergic agonist. Moreover, expression levels in human white adipose tissue (WAT) are inversely correlated with adiposity, and overexpression in primary fat cells stimulates cellular thermogenesis, which is dependent. Fat-specific transgenic mice gain less weight and have smaller fat pads due to increased thermogenesis of brown and beige fat. Moreover, transgenic mice displayed lower fasting blood glucose levels and improved glucose tolerance and insulin sensitivity under the high-fat diet condition. Conversely, mutation in brown adipocytes reduces the expression of thermogenic genes, causing a reduction in cellular respiration. -mutant mice exhibited obesity and cold sensitivity due to impairments in the thermogenic function of fat. Finally, fat deletion inhibits the β3 agonist-mediated induction of WAT browning and brown adipose tissue thermogenesis. Mechanistically, cold-inducible stimulates expression of Pgc1α, a master regulator of fat thermogenesis, by a direct binding to its gene promoter region, subsequently promoting energy expenditure. The current study reveals a critical role for KLF9 in mediating thermogenesis of brown and beige fat.
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http://dx.doi.org/10.2337/db19-1153DOI Listing
December 2020

Flash Graphene Morphologies.

ACS Nano 2020 Oct 16;14(10):13691-13699. Epub 2020 Sep 16.

Flash Joule heating (FJH) can convert almost any carbon-based precursor into bulk quantities of graphene. This work explores the morphologies and properties of flash graphene (FG) generated from carbon black. It is shown that FG is partially comprised of sheets of turbostratic FG (tFG) that have a rotational mismatch between neighboring layers. The remainder of the FG is wrinkled graphene sheets that resemble nongraphitizing carbon. To generate high quality tFG sheets, a FJH duration of 30-100 ms is employed. Beyond 100 ms, the turbostratic sheets have time to AB-stack and form bulk graphite. Atomistic simulations reveal that generic thermal annealing yields predominantly wrinkled graphene which displays minimal to no alignment of graphitic planes, as opposed to the high-quality tFG that might be formed under the direct influence of current conducted through the material. The tFG was easily exfoliated via shear, hence the FJH process has the potential for bulk production of tFG without the need for pre-exfoliation using chemicals or high energy mechanical shear.
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http://dx.doi.org/10.1021/acsnano.0c05900DOI Listing
October 2020

Cost Modifications during the Early Years of the Use of the National Cardiovascular Data Registry for Quality Improvement.

Clinics (Sao Paulo) 2020 26;75:e1708. Epub 2020 Aug 26.

UnitedHealth Group Brazil, Rio de Janeiro, RJ, BR.

Objectives: Quality improvement (QI) initiatives based on data from international registries have been reported previously; however, there is a lack of information on the impact on the costs of medical care associated with the use of these tools.

Methods: Patients admitted due to myocardial infarction (MI), included in the ACTION Registry® and CathPCI Registry®, in a private Brazilian hospital (i.e., the reference hospital) were analyzed. The costs of care of these patients were compared to the costs of MI admissions in nine similar hospitals not included in the same QI program. Regression models were used to analyze the cost change over time between the two groups of hospitals. Readmission rates were compared using logistic regression, adjusting for the same variables as in the cost model.

Results: Overall, the annual medical cost inflation in Brazil was higher than the annual cost trend in the reference hospital during the period of analysis. Moreover, the annual in-hospital costs indicate that the reference hospital has a statistically significant 6% lower cost trend for patients with acute MI, compared to patients with the same diagnostic code in the comparison hospitals group, in an adjusted analysis (p-value=0.041). Using multivariable analysis, the readmission rates were also found to be significantly lower in the reference hospital than in the comparison hospitals, with an odds ratio of 0.68 (p-value=0.042).

Conclusion: The use of the NCDR® as a benchmark to guide QI programs outside the United States was associated with the positive impact of bending the cost curve to below that of national medical inflation and the comparison hospitals' costs, with a lower incidence of hospital readmission.
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http://dx.doi.org/10.6061/clinics/2020/e1708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442399PMC
November 2020

Author Correction: Role of HDAC9-FoxO1 Axis in the Transcriptional Program Associated with Hepatic Gluconeogenesis.

Sci Rep 2020 May 28;10(1):8989. Epub 2020 May 28.

Jiangsu Province Key Lab of Human Functional Genomics, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, 210029, China.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41598-020-66085-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253407PMC
May 2020

Laminated Laser-Induced Graphene Composites.

ACS Nano 2020 Jul 28;14(7):7911-7919. Epub 2020 May 28.

Department of Engineering, San Jacinto College South, 13735 Beamer Road, Houston, Texas 77089, United States.

Laser-induced graphene (LIG) is a porous graphene foam generated by lasing carbon-based precursors. Compositing LIG expands the spectrum of applications for which the material may be used. Techniques for scale-up of LIG composites will be essential as the technology approaches commercialization. Roll-to-roll processing is of special interest, as precisely controlled patterning can be performed in conjunction with continuous formation of composites. Here, we demonstrate a simple lamination compositing method that is compatible with roll-to-roll processing and yields functional, patterned, and multilayered LIG composites with various thermoplastic films. Multiple lamination steps are used to encapsulate LIG within composites. We also demonstrate several applications for LIG that have been enabled by the lamination compositing technique. These include robust flexible electrodes generated through laminating copper foil strips into the LIG composite, LIG-based triboelectric nanogenerators to harvest waste mechanical energy, antimicrobial LIG composite bandages with varying hydrophobicity, and LIG puncture detectors.
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http://dx.doi.org/10.1021/acsnano.0c02835DOI Listing
July 2020

The Patatin-Like Phospholipase Domain Containing Protein 7 Facilitates VLDL Secretion by Modulating ApoE Stability.

Hepatology 2020 11 25;72(5):1569-1585. Epub 2020 Oct 25.

The Key Laboratory of Rare Metabolic Disease, Nanjing Medical University, Nanjing, China.

Background And Aims: The regulation of hepatic very-low-density lipoprotein (VLDL) secretion is vital for lipid metabolism whose pathogenetic status is involved in fatty liver disease and dyslipidemia seen in hepatic steatosis. Accumulated evidence suggest that apolipoprotein E (ApoE) is closely related to hepatic VLDL secretion. Here, we report that the expression of patatin-like phospholipase domain containing protein 7 (PNPLA7) is strongly induced by hepatic steatosis and positively correlates with plasma triacylglycerol (TAG) levels in the human subjects, whereas the role of PNPLA7 in hepatic VLDL secretion is unknown.

Approach And Results: Herein, with genetic manipulation in the mice, the deficiency of hepatic PNPLA7 expression resulted in reduced VLDL secretion accompanied by enhanced hepatic lipid accumulation and decreased hepatic ApoE expression. Furthermore, knockdown of PNPLA7 in the livers of the db/db mice also resulted in significant reduction in plasma TAG level but aggravated hepatic steatosis. Importantly, we observed that PNPLA7 interacted with ApoE and presumably at the site of endoplasmic reticulum. Mechanistically, we have shown that PNPLA7 could modulate polyubiquitination and proteasomal-mediated degradation of ApoE. Overexpressed ApoE restored the impaired VLDL-TAG metabolism in PNPLA7-knockdown primary hepatocytes.

Conclusion: PNPLA7 plays a critical role in regulating hepatic VLDL secretion by modulating ApoE stability through its interaction with ApoE.
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http://dx.doi.org/10.1002/hep.31161DOI Listing
November 2020

Chronic hepatitis C virus infection impairs insulin secretion by regulation of p38δ MAPK-dependent exocytosis in pancreatic β-cells.

Clin Sci (Lond) 2020 03;134(5):529-542

Jiangsu Province Key Lab of Human Functional Genomics, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing 210029, China.

Chronic hepatitis C virus (HCV) infection has a close association with type 2 diabetes mellitus. Although the mechanisms of insulin resistance in chronic hepatitis C (CHC) patients have been extensively studied, little attention has been given to the role of β-cell function in HCV-associated diabetes. Here, we analysed β-cell function in CHC patients and HCV-infected mouse model and found in addition to insulin resistance, impaired pancreatic β-cell function occurred in CHC patients and HCV-infected C/OTg mice, not only in diabetic individuals but also in individuals with impaired fasting glucose levels. Both first-phase and second-phase insulin secretion were impaired, at least partially due to the reduction of exocytosis of secretory insulin-containing granules following HCV infection. Up-regulated p38δ in HCV-infected β-cells resulted in inactivation of protein kinase D (PKD), which was responsible for impaired insulin secretory capacity of β-cells. Thus, impaired insulin secretion due to HCV infection in β-cells contributes to HCV-associated type 2 diabetes. These findings provided a new inspiration for the important prognostic and therapeutic implications in the management of CHC patients with impaired fasting glucose.
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http://dx.doi.org/10.1042/CS20190900DOI Listing
March 2020

Regulation of heterotopic ossification by monocytes in a mouse model of aberrant wound healing.

Nat Commun 2020 02 5;11(1):722. Epub 2020 Feb 5.

Section of Plastic Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI, 48109, USA.

Heterotopic ossification (HO) is an aberrant regenerative process with ectopic bone induction in response to musculoskeletal trauma, in which mesenchymal stem cells (MSC) differentiate into osteochondrogenic cells instead of myocytes or tenocytes. Despite frequent cases of hospitalized musculoskeletal trauma, the inflammatory responses and cell population dynamics that regulate subsequent wound healing and tissue regeneration are still unclear. Here we examine, using a mouse model of trauma-induced HO, the local microenvironment of the initial post-injury inflammatory response. Single cell transcriptome analyses identify distinct monocyte/macrophage populations at the injury site, with their dynamic changes over time elucidated using trajectory analyses. Mechanistically, transforming growth factor beta-1 (TGFβ1)-producing monocytes/macrophages are associated with HO and aberrant chondrogenic progenitor cell differentiation, while CD47-activating peptides that reduce systemic macrophage TGFβ levels and help ameliorate HO. Our data thus implicate CD47 activation as a therapeutic approach for modulating monocyte/macrophage phenotypes, MSC differentiation and HO formation during wound healing.
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http://dx.doi.org/10.1038/s41467-019-14172-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7002453PMC
February 2020

Polar Coordinate Description of Blood Pressure Measurements and Implications for Sex-Specific and Personalized Analysis.

Annu Int Conf IEEE Eng Med Biol Soc 2019 Jul;2019:502-505

Vascular properties and their associated impact on cardiovascular risk factors are often evaluated by metrics such as pulse pressure (PP) and the augmentation index (AIx). All derived metrics are essentially based on the combination of blood pressure recordings. These clinically used metrics typically concern a difference (as in PP) or a ratio (as in AIx). A polar coordinate description reveals the companion (C) of the traditional metric. The aim of this study is to evaluate the impact of PPC and AIxC by analyzing both patient data and a detailed data set on healthy children derived from the literature.Companions are calculated using the Pythagorean theorem, and show that PPC is related to mean arterial pressure, thus complementing the biomarker PP. Also, inflection pressure is tied to systolic pressure, implying a possible simplification of obtaining the numerical value of AIx. Outcomes for adults and children are comparable. We conclude that derived metrics such as PP and AIx are incomplete. The associated companion metrics PPC and AIxC can easily be calculated. They add clinically relevant information without the need to perform additional measurements. Combination of traditional and the newly described companion metrics permits more precise characterization of individual patients.
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http://dx.doi.org/10.1109/EMBC.2019.8857346DOI Listing
July 2019

Actin protrusions push at apical junctions to maintain E-cadherin adhesion.

Proc Natl Acad Sci U S A 2020 01 23;117(1):432-438. Epub 2019 Dec 23.

Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801

Cadherin-mediated cell-cell adhesion is actin-dependent, but the precise role of actin in maintaining cell-cell adhesion is not fully understood. Actin polymerization-dependent protrusive activity is required to push distally separated cells close enough to initiate contact. Whether protrusive activity is required to maintain adhesion in confluent sheets of epithelial cells is not known. By electron microscopy as well as live cell imaging, we have identified a population of protruding actin microspikes that operate continuously near apical junctions of polarized Madin-Darby canine kidney (MDCK) cells. Live imaging shows that microspikes containing E-cadherin extend into gaps between E-cadherin clusters on neighboring cells, while reformation of cadherin clusters across the cell-cell boundary correlates with microspike withdrawal. We identify Arp2/3, EVL, and CRMP-1 as 3 actin assembly factors necessary for microspike formation. Depleting these factors from cells using RNA interference (RNAi) results in myosin II-dependent unzipping of cadherin adhesive bonds. Therefore, actin polymerization-dependent protrusive activity operates continuously at cadherin cell-cell junctions to keep them shut and to prevent myosin II-dependent contractility from tearing cadherin adhesive contacts apart.
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http://dx.doi.org/10.1073/pnas.1908654117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6955295PMC
January 2020

Mesenchymal VEGFA induces aberrant differentiation in heterotopic ossification.

Bone Res 2019 10;7:36. Epub 2019 Dec 10.

1Department of Surgery, University of Michigan, Ann Arbor, MI 48109 USA.

Heterotopic ossification (HO) is a debilitating condition characterized by the pathologic formation of ectopic bone. HO occurs commonly following orthopedic surgeries, burns, and neurologic injuries. While surgical excision may provide palliation, the procedure is often burdened with significant intra-operative blood loss due to a more robust contribution of blood supply to the pathologic bone than to native bone. Based on these clinical observations, we set out to examine the role of vascular signaling in HO. Vascular endothelial growth factor A (VEGFA) has previously been shown to be a crucial pro-angiogenic and pro-osteogenic cue during normal bone development and homeostasis. Our findings, using a validated mouse model of HO, demonstrate that HO lesions are highly vascular, and that VEGFA is critical to ectopic bone formation, despite lacking a contribution of endothelial cells within the developing anlagen.
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http://dx.doi.org/10.1038/s41413-019-0075-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6904752PMC
December 2019

Disruption of Neutrophil Extracellular Traps (NETs) Links Mechanical Strain to Post-traumatic Inflammation.

Front Immunol 2019 24;10:2148. Epub 2019 Oct 24.

Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, United States.

Inflammation after trauma is both critical to normal wound healing and may be highly detrimental when prolonged or unchecked with the potential to impair physiologic healing and promote pathology. Mechanical strain after trauma is associated with impaired wound healing and increased inflammation. The exact mechanisms behind this are not fully elucidated. Neutrophil extracellular traps (NETs), a component of the neutrophil response to trauma, are implicated in a range of pro-inflammatory conditions. In the current study, we evaluated their role in linking movement and inflammation. We found that a link exists between the disruption and amplification of NETs which harbors the potential to regulate the wound's response to mechanical strain, while leaving the initial inflammatory signal necessary for physiologic wound healing intact.
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http://dx.doi.org/10.3389/fimmu.2019.02148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6821718PMC
October 2020

Short-wave infrared light imaging measures tissue moisture and distinguishes superficial from deep burns.

Wound Repair Regen 2020 03 4;28(2):185-193. Epub 2019 Dec 4.

Department of Surgery, University of Michigan, Ann Arbor, Michigan.

Existing clinical approaches and tools to measure burn tissue destruction are limited resulting in misdiagnosis of injury depth in over 40% of cases. Thus, our objective in this study was to characterize the ability of short-wave infrared (SWIR) imaging to detect moisture levels as a surrogate for tissue viability with resolution to differentiate between burns of various depths. To accomplish our aim, we constructed an imaging system consisting of a broad-band Tungsten light source; 1,200-, 1,650-, 1,940-, and 2,250-nm wavelength filters; and a specialized SWIR camera. We initially used agar slabs to provide a baseline spectrum for SWIR light imaging and demonstrated the differential absorbance at the multiple wavelengths, with 1,940 nm being the highest absorbed wavelength. These spectral bands were then demonstrated to detect levels of moisture in inorganic and in vivo mice models. The multiwavelength SWIR imaging approach was used to diagnose depth of burns using an in vivo porcine burn model. Healthy and injured skin regions were imaged 72 hours after short (20 seconds) and long (60 seconds) burn application, and biopsies were extracted from those regions for histologic analysis. Burn depth analysis based on collagen coagulation histology confirmed the formation of superficial and deep burns. SWIR multispectral reflectance imaging showed enhanced intensity levels in long burned regions, which correlated with histology and distinguished between superficial and deep burns. This SWIR imaging method represents a novel, real-time method to objectively distinguishing superficial from deep burns.
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http://dx.doi.org/10.1111/wrr.12779DOI Listing
March 2020

Self-Sterilizing Laser-Induced Graphene Bacterial Air Filter.

ACS Nano 2019 10 4;13(10):11912-11920. Epub 2019 Oct 4.

Institute of Biosciences and Technology , Texas A&M Health Science Center , Houston , Texas 77030 , United States.

Nosocomial infections transmitted through airborne, droplet, aerosol, and particulate-transported modes pose substantial infection risks to patients and healthcare employees. In this study, we demonstrate a self-cleaning filter comprised of laser-induced graphene (LIG), a porous conductive graphene foam formed through photothermal conversion of a polyimide film by a commercial CO laser cutter. LIG was shown to capture particulates and bacteria. The bacteria cannot proliferate even when submerged in culture medium. Through a periodic Joule-heating mechanism, the filter readily reaches >300 °C. This destroys any microorganisms including bacteria, along with molecules that can cause adverse biological reactions and diseases. These molecules include pyrogens, allergens, exotoxins, endotoxins, mycotoxins, nucleic acids, and prions. Capitalizing on the high surface area and thermal stability of LIG, the utility of graphene for reduction of nosocomial infection in hospital settings is suggested.
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http://dx.doi.org/10.1021/acsnano.9b05983DOI Listing
October 2019

The metabolic regulator small heterodimer partner contributes to the glucose and lipid homeostasis abnormalities induced by hepatitis C virus infection.

Metabolism 2019 11 8;100:153954. Epub 2019 Aug 8.

Jiangsu Province Key Lab of Human Functional Genomics, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing 210029, China. Electronic address:

Background: Chronic hepatitis C virus (HCV) infection can predispose the host to metabolic abnormalities. The orphan nuclear receptor small heterodimer partner (SHP; NR0B2) has been identified as a key transcriptional regulatory factor of genes involved in diverse metabolic pathways. The protective effects of SHP against HCV-induced hepatic fibrosis have been reported. However, the exact mechanisms of its role on metabolism are largely unknown. We investigated the role of hepatic SHP in regulating glucose and lipid homeostasis, particularly in the metabolic stress response caused by HCV infection.

Materials And Methods: Gluconeogenesis and lipogenesis levels and SHP expression were measured in HCV-infected cells, as well as in liver samples from HCV-infected patients and persistently HCV-infected mice.

Results: We demonstrated that SHP is involved in gluconeogenesis via the acetylation of the Forkhead box O (FoxO) family transcription factor FoxO1, which is mediated by histone deacetylase 9 (HDAC9). Meanwhile, SHP regulates lipogenesis in the liver via suppressing the induction of sterol regulatory element-binding protein-1c (SREBP-1c) expression by the SUMOylation of Liver X receptor α (LXRα) at the SREBP-1c promoter. In particular, SHP can be strongly reduced upon stimulation, such as by HCV infection. The SHP expression levels were decreased in the livers from the CHC patients and persistently HCV-infected mice, and a negative correlation was observed between the SHP expression levels and gluconeogenic or lipogenic activities, emphasizing the clinical relevance of these results.

Conclusions: Our results suggest that SHP is involved in HCV-induced abnormal glucose and lipid homeostasis and that SHP could be a major target for therapeutic interventions targeting HCV-associated metabolic diseases.
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http://dx.doi.org/10.1016/j.metabol.2019.153954DOI Listing
November 2019

Long non-coding RNA Bhmt-AS attenuates hepatic gluconeogenesis via modulation of Bhmt expression.

Biochem Biophys Res Commun 2019 08 14;516(1):215-221. Epub 2019 Jun 14.

The Key Laboratory of Rare Metabolic Disease, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, 211166, China; The Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, Jiangsu, 211166, China. Electronic address:

Dysregulation of gluconeogenesis contributes to the pathogenesis of metabolic disease, such as type-2 diabetes. The role of long non-coding RNAs (lncRNAs) in the pathogenesis of diabetes has recently received increased attention. In the present study, we identified a novel lncRNA, betaine-homocysteine methyltransferase-antisense (Bhmt-AS), and examined its expression patterns under pathophysiological conditions. Our results revealed that the expression of Bhmt-AS was significantly increased in the livers of fasted and db/db mice and was induced by gluconeogenic hormonal stimuli. The Bhmt-AS was also shown to be a concordant regulator of Bhmt expression. Functionally, depletion of Bhmt-AS suppressed hepatic glucose production both in vivo and in vitro. Adenovirus-mediated hepatic knockdown of Bhmt-AS improved pyruvate tolerance, glucose tolerance, and insulin sensitivity. Furthermore, overexpression of Bhmt restored the decreased glucose production caused by knockdown of Bhmt-AS in primary hepatocytes. Taken together, we uncovered a novel antisense lncRNA (Bhmt-AS) that is co-expressed with Bhmt and concordantly and specifically regulates Bhmt expression both in vitro and in vivo to regulate hepatic gluconeogenesis.
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http://dx.doi.org/10.1016/j.bbrc.2019.06.008DOI Listing
August 2019

Laser-Induced Graphene Triboelectric Nanogenerators.

ACS Nano 2019 Jun 29;13(6):7166-7174. Epub 2019 May 29.

Triboelectric nanogenerators (TENGs) show exceptional promise for converting wasted mechanical energy into electrical energy. This study investigates the use of laser-induced graphene (LIG) composites as an exciting class of triboelectric materials in TENGs. Infrared laser irradiation is used to convert the surfaces of the two carbon sources, polyimide (PI) and cork, into LIG. This gives the bilayer composite films the high conductivity associated with LIG and the triboelectric properties of the carbon source. A LIG/PI composite is used to fabricate TENGs based on conductor-to-dielectric and metal-free dielectric-to-dielectric device geometries with open-circuit voltages >3.5 kV and peak power >8 mW. Additionally, a single sheet of PI is converted to a metal-free foldable TENG. The LIG is also embedded within a PDMS matrix to form a single-electrode LIG/PDMS composite TENG. This single-electrode TENG is highly flexible and stretchable and was used to generate power from mechanical contact with skin. The LIG composites present a class of triboelectric materials that can be made from naturally occurring and synthetic carbon sources.
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http://dx.doi.org/10.1021/acsnano.9b02596DOI Listing
June 2019

Investigation into the diversity in the fractal dimensions of arterioles and venules in a microvascular network - A quantitative analysis.

Microvasc Res 2019 09 7;125:103882. Epub 2019 May 7.

Department of Biomedical Engineering, MOE Key Laboratory of Biomedical Engineering, Zhejiang University, 38 Zheda Road, Hangzhou 310027, China. Electronic address:

Fractal dimension is a robust fractal parameter for estimating the morphology of vascular networks. It reflects the property of vascular networks that may vary and thus, differentiate between individual networks and/or identify physiological and pathological conditions. As such, fractal dimension differs also between arteriolar and venular compartments, yet the underlying reason is so far unclear. In order to understand the mechanisms behind these differences, we quantitatively analyzed the impacts of vessel attributes on the fractal dimension. Fractal dimension and vessel attributes given by vessel density (VD), vessel length density (VL), and diameter index (DI=VD/VL) were analyzed in three microvascular networks of the rat mesentery, which were reconstructed from experimental data. The results show that differences in diameter between arterioles and venules are primarily responsible for arterio-venous differences in fractal dimension. Moreover, multiple linear regression analysis demonstrates that the sensitivity of the variation of fractal dimension to vessel length and diameter varies with the type of the vessels. While the change of vessel length contributes 57.8 ± 3.4% to the variation of arteriolar dimension, vessel diameter contributes 63.9 ± 4.8% to the variation of venular dimension. The present study provides an explanation for the different fractal dimension and dimension variation in arteriolar and venular compartments. It highlights the importance of estimating the fractal dimensions of arterioles and venules separately, which will enhance the ability of feature extraction by fractal analysis in physiological and clinical application.
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http://dx.doi.org/10.1016/j.mvr.2019.103882DOI Listing
September 2019

Cideb controls sterol-regulated ER export of SREBP/SCAP by promoting cargo loading at ER exit sites.

EMBO J 2019 04 11;38(8). Epub 2019 Mar 11.

State Key Laboratory of Membrane Biology and Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China

SREBPs are master regulators of lipid homeostasis and undergo sterol-regulated export from ER to Golgi apparatus for processing and activation via COPII-coated vesicles. While COPII recognizes SREBP through its escort protein SCAP, factor(s) specifically promoting SREBP/SCAP loading to the COPII machinery remains unknown. Here, we show that the ER/lipid droplet-associated protein Cideb selectively promotes the loading of SREBP/SCAP into COPII vesicles. Sterol deprivation releases SCAP from Insig and enhances ER export of SREBP/SCAP by inducing SCAP-Cideb interaction, thereby modulating sterol sensitivity. Moreover, Cideb binds to the guanine nucleotide exchange factor Sec12 to enrich SCAP/SREBP at ER exit sites, where assembling of COPII complex initiates. Loss of Cideb inhibits the cargo loading of SREBP/SCAP, reduces SREBP activation, and alleviates diet-induced hepatic steatosis. Our data point to a linchpin role of Cideb in regulated ER export of SREBP and lipid homeostasis.
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http://dx.doi.org/10.15252/embj.2018100156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6463267PMC
April 2019

Coordinating Tissue Regeneration Through Transforming Growth Factor-β Activated Kinase 1 Inactivation and Reactivation.

Stem Cells 2019 06 14;37(6):766-778. Epub 2019 Mar 14.

School of Dentistry, University of Michigan, Ann Arbor, Michigan, USA.

Aberrant wound healing presents as inappropriate or insufficient tissue formation. Using a model of musculoskeletal injury, we demonstrate that loss of transforming growth factor-β activated kinase 1 (TAK1) signaling reduces inappropriate tissue formation (heterotopic ossification) through reduced cellular differentiation. Upon identifying increased proliferation with loss of TAK1 signaling, we considered a regenerative approach to address insufficient tissue production through coordinated inactivation of TAK1 to promote cellular proliferation, followed by reactivation to elicit differentiation and extracellular matrix production. Although the current regenerative medicine paradigm is centered on the effects of drug treatment ("drug on"), the impact of drug withdrawal ("drug off") implicit in these regimens is unknown. Because current TAK1 inhibitors are unable to phenocopy genetic Tak1 loss, we introduce the dual-inducible COmbinational Sequential Inversion ENgineering (COSIEN) mouse model. The COSIEN mouse model, which allows us to study the response to targeted drug treatment ("drug on") and subsequent withdrawal ("drug off") through genetic modification, was used here to inactivate and reactivate Tak1 with the purpose of augmenting tissue regeneration in a calvarial defect model. Our study reveals the importance of both the "drug on" (Cre-mediated inactivation) and "drug off" (Flp-mediated reactivation) states during regenerative therapy using a mouse model with broad utility to study targeted therapies for disease. Stem Cells 2019;37:766-778.
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http://dx.doi.org/10.1002/stem.2991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6542699PMC
June 2019

Positional ischaemia of transplant kidney: A rare cause of early graft dysfunction.

J Clin Ultrasound 2019 Jun 18;47(5):308-311. Epub 2019 Feb 18.

Center for Transplant and Renal Research, The Westmead Institute of Medical Research, Westmead, New South Wales, Australia.

Kinking of the kidney transplant vessels late after the operation is a rare complication that can lead to significant morbidity and mortality. We present a case of positional ischemia of the renal allograft resulting from dynamic and positional kinking of the graft vasculature, which was diagnosed by ultrasonography with the patient standing. The graft was repositioned into the sub-rectus pocket and the ischaemic injury resolved.
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http://dx.doi.org/10.1002/jcu.22711DOI Listing
June 2019

Interpretation of a new biomarker for the right ventricle introduced to evaluate the severity of pulmonary arterial hypertension.

Pulm Circ 2019 Apr-Jun;9(2):2045894019826945

4 Department of Emergency Medicine, Drexel University College of Medicine, Philadelphia PA, USA.

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http://dx.doi.org/10.1177/2045894019826945DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6540503PMC
January 2019

Myocardial oxygen balance during acute normovolemic hemodilution: A novel compartmental modeling approach.

Comput Biol Med 2019 02 12;105:16-26. Epub 2018 Dec 12.

Department of Biomedical and Chemical Engineering and Sciences, Florida Institute of Technology, Melbourne, FL, USA. Electronic address:

Background: Hemodilution was introduced initially as a blood conservation technique to reduce allogeneic blood transfusion in patients undergoing surgical procedures. Although the technique has been approved by the National Institute of Health consensus panel, limits of hemodilution under anesthetic conditions have not been established as they have in animal models.

Methods: A novel multi-compartmental modeling approach has been proposed that includes the effect of anesthesia to quantify the effect of hemodilution on myocardial oxygen balance during myocardial ischemia.

Results: The results showed that isovolemic hemodilution would cause detrimental effects around a hematocrit of 15%. Even though the fall in oxygen content caused by the decrease in hemoglobin concentration was compensated by an increase in coronary blood flow induced by hypoxic vasodilation and decreased viscosity, the endocardial tissue received less oxygen compared to the epicardial regions, and this sub-endocardial ischemia eventually led to cardiac failure. Statistical analysis also showed that the type of acellular replacement fluid failed to affect the heart rate, the stroke index or the cardiac index during hemodilution, and supplemental oxygen improved the endocardial oxygen supply.

Conclusion: The model validates the clinical conclusions that sub-endocardial ischemia causes cardiac failure under extreme hemodilution conditions and the model can also be easily integrated into other human simulators.
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http://dx.doi.org/10.1016/j.compbiomed.2018.12.009DOI Listing
February 2019