Targeting SLC22A5 fosters mitophagy inhibition-mediated macrophage immunity against septic acute kidney injury upon CD47-SIRPα axis blockade.

Efferocytosis of apoptotic neutrophils (PMNs) by macrophages is helpful for inflammation resolution and injury repair, but the role of efferocytosis in intrinsic nature of macrophages during septic acute kidney injury (AKI) remains unknown. Here we report that CD47 and signal regulatory protein alpha (SIRPα)-the anti-efferocytotic 'don't eat me' signals-are highly expressed in peripheral blood mononuclear cells (PBMCs) from patients with septic AKI and kidney samples from mice with polymicrobial sepsis and endotoxin shock. Conditional knockout (CKO) of in macrophages ameliorates AKI and systemic inflammation response in septic mice, accompanied by an escalation in mitophagy inhibition of macrophages.

Alcohol dehydrogenase 1 is a tubular mitophagy-dependent apoptosis inhibitor against septic acute kidney injury.

Alcohol dehydrogenase 1 (ADH1) is an alcohol-oxidizing enzyme with poorlydefined biology. Here we report that ADH1 is highly expressed in kidneys of mice with lethal endotoxemia and is transcriptionally upregulated in tubular cells by lipopolysaccharide (LPS) stimuli through TLR4/NF-κB cascade. The Adh1 knockout (Adh1) mice with lethal endotoxemia displayed increased susceptibility to acute kidney injury (AKI) but not systemic inflammatory response.

Current status and prospects of basic research and clinical application of mesenchymal stem cells in acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is a common and clinically devastating disease that causes respiratory failure. Morbidity and mortality of patients in intensive care units are stubbornly high, and various complications severely affect the quality of life of survivors. The pathophysiology of ARDS includes increased alveolar-capillary membrane permeability, an influx of protein-rich pulmonary edema fluid, and surfactant dysfunction leading to severe hypoxemia.

Auto- and paracrine rewiring of NIX-mediated mitophagy by insulin-like growth factor-binding protein 7 in septic AKI escalates inflammation-coupling tubular damage.

Aims: Inflammation-coupling tubular damage (ICTD) contributes to pathogenesis of septic acute kidney injury (AKI), in which insulin-like growth factor-binding protein 7 (IGFBP-7) serves as a biomarker for risk stratification. The current study aims to discern how IGFBP-7 signalling influences ICTD, the mechanisms that underlie this process and whether blockade of the IGFBP-7-dependent ICTD might have therapeutic value for septic AKI.

Materials And Methods: In vivo characterization was carried out in B6/JGpt-Igfbp7/Gpt mice subjected to cecal ligation and puncture (CLP).

Tubule-mitophagic secretion of SerpinG1 reprograms macrophages to instruct anti-septic acute kidney injury efficacy of high-dose ascorbate mediated by NRF2 transactivation.

High-dose ascorbate confers tubular mitophagy responsible for septic acute kidney injury (AKI) amelioration, yet its biological roles in immune regulation remain poorly understood. The role of tubular mitophagy in macrophage polarization upon high-dose ascorbate treatment was assessed by fluorescence-activated cell sorter analysis (FACS) and by immunofluorescence in AKI models of LPS-induced endotoxemia (LIE) from ; mice. The underlying mechanisms were revealed by RNA-sequencing, gene set enrichment analysis (GSEA), luciferase reporter, chromatin immunoprecipitation (ChIP) and adeno-associated viral vector serotype 9 (AAV9) delivery assays.

Serum calcium channel subunit α2δ-1 concentrations and outcomes in patients with acute spontaneous intracerebral hemorrhage.

Background: Voltage-gated calcium channel subunit α2δ-1 plays an important role in acute brain injury. We attempted to investigate whether serum α2δ-1 subunit concentrations are correlated with severity and prognosis following intracerebral hemorrhage (ICH).

Methods: Serum α2δ-1 subunit concentrations were quantified in 103 ICH patients and 103 healthy controls.

Resveratrol alleviates intestinal mucosal barrier dysfunction in dextran sulfate sodium-induced colitis mice by enhancing autophagy.

Background: Intestinal mucosal barrier dysfunction plays an important role in the pathogenesis of ulcerative colitis (UC). Recent studies have revealed that impaired autophagy is associated with intestinal mucosal dysfunction in the mucosa of colitis mice. Resveratrol exerts anti-inflammatory functions by regulating autophagy.

The use of a double-layer platinum black-conducting polymer coating for improvement of neural recording and mitigation of photoelectric artifact.

The impedance of electrode and photostimulation artifacts (short-duration and high-amplitude spikes) are still hindering the employment of silicon-based neural probe in optogenetics. A fiber-based optrode modified with a double-layer platinum black-poly (3,4ethylenedioxythiophene) PEDOT/poly (4-styrenesulfonate) PSS (Pt-PP) coating has been developed for improvement of neural recording quality and mitigation of photoelectric artifact simultaneously. The Pt-PP coating was made by layer-by-layer electrochemical deposition followed by the ultrasonication and Cyclic Voltammetry (CV) scanning to verify its mechanical and electrochemical stability.

Regulation of Fn14 stability by SCF during septic acute kidney injury.

Acute kidney injury (AKI) initiated by sepsis remains a thorny problem despite recent advancements in its clinical management. Having been found to be activated during AKI, fibroblast growth factor-inducible molecule 14 (Fn14) may be a potential therapeutic target because of its involvement in the molecular basis of injury. Here, we report that LPS induces apoptosis of mouse cortical tubule cells mediated by Fn14, for which simultaneous Toll-like receptor (TLR)4 activation is required.

Productive transcription of miR-124-3p by RelA and RNA polymerase II directs RIP1 ubiquitination-dependent apoptosis resistance during hypoxia.

The K63-linked ubiquitination of RIP1 coordinates survival/death homeostasis by driving transcription of genes downstream of RelA. Previously, we demonstrated that EGF-dependent RelA transactivation overcomes hypoxia-initiated apoptosis, yet the underlying mechanisms remain mysterious. We report here that UBXN1 deficiency empowers apoptosis resistance against hypoxia through triggering IκBα degradation, for which K63-linked ubiquitination of RIP1 is required.

Three-dimensional drivable optrode array for high-resolution neural stimulations and recordings in multiple brain regions.

The brain-computer interface (BCI) devices are of prime important for study of nervous system as well as diagnosis and treatment of neurological disorders. To meet the needs of the BCI devices in high-density integration and multi-functionalization, 3-dimensional (3D) drivable optrode array with laser diodes (LDs) coupled waveguides was developed. The unique device realizes the 3D integration of the optrodes and avoids fiber tangle and tissue heating by adopting LD coupled waveguide structure.

Pharmacological Inhibition of PTEN Restores Remote Ischemic Postconditioning Cardioprotection in Hypercholesterolemic Mice: Potential Role of PTEN/AKT/GSK3β SIGNALS.

Although remote ischemic postconditioning (RIPC) was shown to confer cardioprotection against myocardial ischemia/reperfusion (I/R) injury in normal animals, whether RIPC-induced cardioprotection is altered in the presence of hypercholesterolemia, a comorbidity with acute myocardial infarction (AMI) patients has yet to be determined. Normal or 2% cholesterol chow was fed to male C57BL/6J mice for 12 weeks to induce hypercholesterolemia, then normal or hypercholesterolemic murine hearts were exposed to AMI by coronary artery ligation. RIPC was induced by four episodes of 5 min femoral artery occlusion followed by 5 min reperfusion immediately after myocardial reperfusion in mice.

Transcriptional downregulation of microRNA-19a by ROS production and NF-κB deactivation governs resistance to oxidative stress-initiated apoptosis.

Cell apoptosis is one of the main pathological alterations during oxidative stress (OS) injury. Previously, we corroborated that nuclear factor-κB (NF-κB) transactivation confers apoptosis resistance against OS in mammalian cells, yet the underlying mechanisms remain enigmatic. Here we report that microRNA-19a (miR-19a) transcriptionally regulated by reactive oxygen species (ROS) production and NF-κB deactivation prevents OS-initiated cell apoptosis through cylindromatosis (CYLD) repression.

Progress in Research of Flexible MEMS Microelectrodes for Neural Interface.

With the rapid development of Micro-electro-mechanical Systems (MEMS) fabrication technologies, many microelectrodes with various structures and functions have been designed and fabricated for applications in biomedical research, diagnosis and treatment through electrical stimulation and electrophysiological signal recording. The flexible MEMS microelectrodes exhibit excellent characteristics in many aspects beyond stiff microelectrodes based on silicon or metal, including: lighter weight, smaller volume, better conforming to neural tissue and lower fabrication cost. In this paper, we reviewed the key technologies in flexible MEMS microelectrodes for neural interface in recent years, including: design and fabrication technology, flexible MEMS microelectrodes with fluidic channels and electrode⁻tissue interface modification technology for performance improvement.

Direct electrodeposition of Graphene enhanced conductive polymer on microelectrode for biosensing application.

Engineering of neural interface with nanomaterials for high spatial resolution neural recording and stimulation is still hindered by materials properties and modification methods. Recently, poly(3,4-ethylene-dioxythiophene) (PEDOT) has been widely used as an electrode-tissue interface material for its good electrochemical property. However, cracks and delamination of PEDOT film under pulse stimulation are found which restrict its long-term applications.

MicroRNA-130b transcriptionally regulated by histone H3 deacetylation renders Akt ubiquitination and apoptosis resistance to 6-OHDA.

Apoptosis of DA neurons is a contributing cause of disability and death for Parkinson's disease (PD). Akt may become a potential therapeutic target for PD since Akt has been deactivated during DA neuron apoptosis. We previously demonstrated that Akt confers apoptosis resistance against 6-OHDA in DA neuron-like PC12 cells, yet the underlying mechanisms accounted for this are not fully understood.

Simultaneous quantification of four metabolites of sulfur mustard in urine samples by ultra-high performance liquid chromatography-tandem mass spectrometry after solid phase extraction.

Four HD urinary metabolites including hydrolysis metabolite thiodiglycol (TDG), glutathione-derived metabolite 1,1'-sulfonylbis[2-S-(N-acetylcysteinyl)ethane] (SBSNAE), as well as the β-lyase metabolites 1,1'-sulfonylbis[2-(methylsulfinyl)ethane] (SBMSE) and 1-methylsulfinyl-2-[2-(methylthio) ethylsulfonyl]ethane (MSMTESE) are considered as important biomarkers for short-term retrospective detection of HD exposure. In this study, a single method for simultaneous quantification of the four HD metabolites in urine samples was developed using ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The four urinary metabolites were simultaneously extracted from urinary samples using a solid phase extraction (SPE) method with high extraction recoveries for all four metabolites varied in the range of 71.

Simultaneous quantification of soman and VX adducts to butyrylcholinesterase, their aged methylphosphonic acid adduct and butyrylcholinesterase in plasma using an off-column procainamide-gel separation method combined with UHPLC-MS/MS.

This work describes a novel and sensitive non-isotope dilution method for simultaneous quantification of organophosphorus nerve agents (OPNAs) soman (GD) and VX adducts to butyrylcholinesterase (BChE), their aged methylphosphonic acid (MeP) adduct and unadducted BChE in plasma exposed to OPNA. OPNA-BChE adducts were isolated with an off-column procainamide-gel separation (PGS) from plasma, and then digested with pepsin into specific adducted FGESAGAAS nonapeptide (NP) biomarkers. The resulting NPs were detected by UHPLC-MS/MS MRM.

Ghrelin protects small intestinal epithelium against sepsis-induced injury by enhancing the autophagy of intestinal epithelial cells.

Background: Ghrelin is a hormone that protects against hypoxic injury of cardiac cells by inducing autophagy, but the role of autophagy in sepsis remains unclear. This study aimed to evaluate whether ghrelin could enhance autophagy in rats with intestinal sepsis.

Methods: The cecal ligation and perforation (CLP) method was used to induce sepsis in Sprague-Dawley rats.

NF-κB-dependent transcriptional upregulation of cyclin D1 exerts cytoprotection against hypoxic injury upon EGFR activation.

Apoptosis of neural cells is one of the main pathological features in hypoxic/ischemic brain injury. Nuclear factor-κB (NF-κB) might be a potential therapeutic target for hypoxic/ischemic brain injury since NF-κB has been found to be inactivated after hypoxia exposure, yet the underlying molecular mechanisms of NF-κB inactivation are largely unknown. Here we report that epidermal growth factor receptor (EGFR) activation prevents neuron-like PC12 cells apoptosis in response to hypoxia via restoring NF-κB-dependent transcriptional upregulation of cyclin D1.

Enhanced Flexible Tubular Microelectrode with Conducting Polymer for Multi-Functional Implantable Tissue-Machine Interface.

Implantable biomedical microdevices enable the restoration of body function and improvement of health condition. As the interface between artificial machines and natural tissue, various kinds of microelectrodes with high density and tiny size were developed to undertake precise and complex medical tasks through electrical stimulation and electrophysiological recording. However, if only the electrical interaction existed between electrodes and muscle or nerve tissue without nutrition factor delivery, it would eventually lead to a significant symptom of denervation-induced skeletal muscle atrophy.

VEGF-mediated NF-κB activation protects PC12 cells from damage induced by hypoxia.

Neuronal apoptosis is a contributing cause of disability and death in cerebral ischemia. Nuclear factor-κB (NF-κB) may become a potential therapeutic target for hypoxic/ischemic neuron damage because NF-κB is inactivated after hypoxia exposure. Vascular endothelial growth factor (VEGF) has been found to improve neurological function recovery in cerebral ischemic injury although the exact molecular mechanisms that underlie the neuroprotective function of VEGF remain largely unknown.

An improved method for retrospective quantification of sulfur mustard exposure by detection of its albumin adduct using ultra-high pressure liquid chromatography-tandem mass spectrometry.

Sulfur mustard (HD) adduct to human serum albumin (ALB) at Cys-34 residue has become an important and long-term retrospective biomarker of HD exposure. Here, a novel, sensitive, and convenient approach for retrospective quantification of HD concentration exposed to plasma was established by detection of the HD-ALB adduct using ultra-high pressure liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) with a novel non-isotope internal standard (IS). The HD-ALB adduct was isolated from HD-exposed plasma with blue Sepharose.

Flexible intramuscular micro tube electrode combining electrical and chemical interface.

With the rapidly developed micromachining technology, various kinds of sophisticated microelectrodes integrated with micro fluidic channels are design and fabricated for not only electrophysiological recording and stimulation, but also chemical drug delivery. As many efforts have been devoted to develop rigid microprobes for neural research of brain, few researchers concentrate on fabrication of flexible microelectrodes for intramuscular electrophysiology and chemical interfacing. Since crude wire electrodes still prevail in functional electrical stimulation (FES) and electromyography (EMG) recording of muscle, here we introduce a flexible micro tube electrode combining electrical and chemical pathway.