Cortactin loss protects against hemin-induced acute lung injury in sickle cell disease.

In patients with sickle cell disease (SCD), acute chest syndrome (ACS) is a common form of acute lung injury and a major cause of morbidity and mortality. The pathophysiology of ACS is complex, and hemin, the prosthetic moiety of hemoglobin, has been implicated in endothelial cell (EC) activation and subsequent acute lung injury (ALI) and ACS in vitro and in animal studies. Here, we examined the role of cortactin (CTTN), a cytoskeletal protein that regulates EC function, in response to hemin-induced ALI and ACS. Cortactin heterozygous (Cttn+/-) mice (n = 8) and their wild-type siblings (n = 8) were irradiated and subsequently received bone marrow cells (BMCs) extruded from the femurs of SCD mice (SS) to generate SS Cttn+/- and SS CttnWT chimeras. Following hemoglobin electrophoretic proof of BMC transplantation, the mice received 35 µmol/kg of hemin. Within 24 h, surviving mice were euthanized, and bronchoalveolar fluid (BAL) and lung samples were analyzed. For in vitro studies, human lung microvascular endothelial cells (HLMVECs) were used to determine hemin-induced changes in gene expression and reactive oxygen species (ROS) generation in cortactin deficiency and control conditions. When compared with wild-type littermates, the mortality for SS Cttn+/- mice trended to be lower after hemin infusion and these mice exhibited less severe lung injury and less necroptotic cell death. In vitro studies confirmed that cortactin deficiency is protective against hemin-induced injury in HMLVECs, by decreasing protein expression of p38/HSP27, improving cell barrier function, and decreasing the production of ROS. Further studies examining the role of CTTN in ACS are warranted and may open a new avenue of potential treatment for this devastating disease.

MRSA-induced endothelial permeability and acute lung injury are attenuated by FTY720 S-phosphonate.

Disruption of the lung endothelial barrier is a hallmark of acute respiratory distress syndrome (ARDS), for which no effective pharmacologic treatments exist. Prior work has demonstrated that FTY720 S-phosphonate (Tys), an analog of sphingosine-1-phosphate (S1P) and FTY720, exhibits potent endothelial cell (EC) barrier protective properties. In this study, we investigated the in vitro and in vivo efficacy of Tys against methicillin-resistant Staphylococcus aureus (MRSA), a frequent bacterial cause of ARDS. Tys-protected human lung EC from barrier disruption induced by heat-killed MRSA (HK-MRSA) or staphylococcal α-toxin and attenuated MRSA-induced cytoskeletal changes associated with barrier disruption, including actin stress fiber formation and loss of peripheral VE-cadherin and cortactin. Tys-inhibited Rho and myosin light chain (MLC) activation after MRSA and blocked MRSA-induced NF-κB activation and release of the proinflammatory cytokines, IL-6 and IL-8. In vivo, intratracheal administration of live MRSA in mice caused significant vascular leakage and leukocyte infiltration into the alveolar space. Pre- or posttreatment with Tys attenuated MRSA-induced lung permeability and levels of alveolar neutrophils. Posttreatment with Tys significantly reduced levels of bronchoalveolar lavage (BAL) VCAM-1 and plasma IL-6 and KC induced by MRSA. Dynamic intravital imaging of mouse lungs demonstrated Tys attenuation of HK-MRSA-induced interstitial edema and neutrophil infiltration into lung tissue. Tys did not directly inhibit MRSA growth or viability in vitro. In conclusion, Tys inhibits lung EC barrier disruption and proinflammatory signaling induced by MRSA in vitro and attenuates acute lung injury induced by MRSA in vivo. These results support the potential utility of Tys as a novel ARDS therapeutic strategy.

TAT delivery of a PTEN peptide inhibitor has direct cardioprotective effects and improves outcomes in rodent models of cardiac arrest.

We have recently shown that pharmacologic inhibition of PTEN significantly increases cardiac arrest survival in a mouse model, however, this protection required pretreatment 30 min before the arrest. To improve the onset of PTEN inhibition during cardiac arrest treatment, we have designed a TAT fused cell-permeable peptide (TAT-PTEN9c) based on the C-terminal PDZ binding motif of PTEN for rapid tissue delivery and protection. Western blot analysis demonstrated that TAT-PTEN9c peptide significantly enhanced Akt activation in mouse cardiomyocytes in a concentration- and time-dependent manner. Mice were subjected to 8 min asystolic arrest followed by CPR, and 30 mice with successful CPR were then randomly assigned to receive either saline or TAT-PTEN9c treatment. Survival was significantly increased in TAT-PTEN9c-treated mice compared with that of saline control at 4 h after CPR. The treated mice had increased Akt phosphorylation at 30 min resuscitation with significantly decreased sorbitol content in heart or brain tissues and reduced release of taurine and glutamate in blood, suggesting improved glucose metabolism. In an isolated rat heart Langendorff model, direct effects of TAT-PTEN9c on cardiac function were measured for 20 min following 20 min global ischemia. Rate pressure product was reduced by >20% for both TAT vehicle and nontreatment groups following arrest. Cardiac contractile function was completely recovered with TAT-PTEN9c treatment given at the start of reperfusion. We conclude that TAT-PTEN9c enhances Akt activation and decreases glucose shunting to the polyol pathway in critical organs, thereby preventing osmotic injury and early cardiovascular collapse and death.NEW & NOTEWORTHY We have designed a cell-permeable peptide, TAT-PTEN9c, to improve cardiac arrest survival. It blocked endogenous PTEN binding to its adaptor and enhanced Akt signaling in mouse cardiomyocytes. It improved mouse survival after cardiac arrest, which is related to improved glucose metabolism and reduced glucose shunting to sorbitol in critical organs.

Phosphotyrosyl phosphatase activator facilitates localization of Miranda through dephosphorylation in dividing neuroblasts.

The mechanism for the basal targeting of the Miranda (Mira) complex during the asymmetric division of Drosophila neuroblasts (NBs) is yet to be fully understood. We have identified conserved Phosphotyrosyl phosphatase activator (PTPA) as a novel mediator for the basal localization of the Mira complex in larval brain NBs. In mutant Ptpa NBs, Mira remains cytoplasmic during early mitosis and its basal localization is delayed until anaphase. Detailed analyses indicate that PTPA acts independent of and before aPKC to localize Mira. Mechanistically, our data show that the phosphorylation status of the T591 residue determines the subcellular localization of Mira and that PTPA facilitates the dephosphorylation of T591. Furthermore, PTPA associates with the Protein phosphatase 4 complex to mediate localization of Mira. On the basis of these results, a two-step process for the basal localization of Mira during NB division is revealed: cortical association of Mira mediated by the PTPA-PP4 complex is followed by apical aPKC-mediated basal restriction.

FUS-linked essential tremor associated with motor dysfunction in Drosophila.

Essential tremor (ET) is one of the most common adult-onset neurological disorders which produce motor and non-motor symptoms. To date, there are no gold standard pathological hallmarks of ET, and despite a strong genetic contribution toward ET development, only a few pathogenic mutations have been identified. Recently, a pathogenic FUS-Q290X mutation has been reported in a large ET-affected family; however, the pathophysiologic mechanism underlying FUS-linked ET is unknown. Here, we generated transgenic Drosophila expressing hFUS-WT and hFUS-Q290X and targeted their expression in different tissues. We found that the targeted expression of hFUS-Q290X in the dopaminergic and the serotonergic neurons did not cause obvious neuronal degeneration, but it resulted in motor dysfunction which was accompanied by impairment in the GABAergic pathway. The involvement of the GABAergic pathway was supported by rescue of motor symptoms with gabapentin. Interestingly, we observed gender specific downregulation of GABA-R and NMDA-R expression and reduction in serotonin level. Overexpression of hFUS-Q290X also caused an increase in longevity and this was accompanied by downregulation of the IIS/TOR signalling pathway. Our in vivo studies of the hFUS-Q290X mutation in Drosophila link motor dysfunction to impairment in the GABAergic pathway. Our findings would facilitate further efforts in unravelling the pathophysiology of ET.

A microfluidic indirect competitive immunoassay for multiple and sensitive detection of testosterone in serum and urine.

We demonstrate a microfluidic-based indirect competitive chemiluminescence enzyme immunoassay (MIC) for multiple, sensitive, reliable and rapid detection of testosterone in human serum and urine samples. As MIC can detect biomarkers in a cost-effective and easy-to-operate manner, it may have great potential for clinical diagnosis and point-of-care testing (POCT).

A novel pharmacological strategy by PTEN inhibition for improving metabolic resuscitation and survival after mouse cardiac arrest.

Sudden cardiac arrest (SCA) is a leading cause of death in the United States. Despite return of spontaneous circulation, patients die due to post-SCA syndrome that includes myocardial dysfunction, brain injury, impaired metabolism, and inflammation. No medications improve SCA survival. Our prior work suggests that optimal Akt activation is critical for cooling protection and SCA recovery. Here, we investigate a small inhibitor of PTEN, an Akt-related phosphatase present in heart and brain, as a potential therapy in improving cardiac and neurological recovery after SCA. Anesthetized adult female wild-type C57BL/6 mice were randomized to pretreatment of VO-OHpic (VO) 30 min before SCA or vehicle control. Mice underwent 8 min of KCl-induced asystolic arrest followed by CPR. Resuscitated animals were hemodynamically monitored for 2 h and observed for 72 h. Outcomes included heart pressure-volume loops, energetics (phosphocreatine and ATP from (31)P NMR), protein phosphorylation of Akt, GSK3ß, pyruvate dehydrogenase (PDH) and phospholamban, circulating inflammatory cytokines, plasma lactate, and glucose as measures of systemic metabolic recovery. VO reduced deterioration of left ventricular maximum pressure, maximum rate of change in the left ventricular pressure, and Petco2 and improved 72 h neurological intact survival (50% vs. 10%; P < 0.05). It reduced plasma lactate, glucose, IL-1ß, and Pre-B cell colony enhancing factor, while increasing IL-10. VO increased phosphorylation of Akt and GSK3ß in both heart and brain, and cardiac phospholamban phosphorylation while reducing p-PDH. Moreover, VO improved cardiac bioenergetic recovery. We concluded that pharmacologic PTEN inhibition enhances Akt activation, improving metabolic, cardiovascular, and neurologic recovery with increased survival after SCA. PTEN inhibitors may be a novel pharmacologic strategy for treating SCA.

Clueless regulates aPKC activity and promotes self-renewal cell fate in Drosophila lgl mutant larval brains.

Asymmetric cell division of Drosophila neural stem cells or neuroblasts is an important process which gives rise to two different daughter cells, one of which is the stem cell itself and the other, a committed or differentiated daughter cell. During neuroblast asymmetric division, atypical Protein Kinase C (aPKC) activity is tightly regulated; aberrant levels of activity could result in tumorigenesis in third instar larval brain. We identified clueless (clu), a genetic interactor of parkin (park), as a novel regulator of aPKC activity. It preferentially binds to the aPKC/Bazooka/Partition Defective 6 complex and stabilizes aPKC levels. In clu mutants, Miranda (Mira) and Numb are mislocalized in small percentages of dividing neuroblasts. Adult mutants are short-lived with severe locomotion defects. Clu promotes tumorigenesis caused by loss of function of lethal(2) giant larvae (lgl) in the larval brain. Removal of clu in lgl mutants rescues Mira and Numb mislocalization and restores the enlarged brain size. Western blot analyses indicate that the rescue is due to the down-regulation of aPKC levels in the lgl clu double mutant. Interestingly, the phenotype of the park mutant, which causes Parkinson's Disease-like symptoms in adult flies, is reminiscent of that of clu in neuroblast asymmetric division. Our study provides the first clue for the potential missing pathological link between temporally separated neurogenesis and neurodegeneration events; the minor defects during early neurogenesis could be a susceptible factor contributing to neurodegenerative diseases at later stages of life.

A Fluoride-Rich Solid-Like Electrolyte Stabilizing Lithium Metal Batteries.

To address the problems associated with Li metal anodes, a fluoride-rich solid-like electrolyte (SLE) that combines the benefits of solid-state and liquid electrolytes is presented. Its unique triflate-group-enhanced frame channels facilitate the formation of a functional inorganic-rich solid electrolyte interphase (SEI), which not only improves the reversibility and interfacial charge transfer of Li anodes but also ensures uniform and compact Li deposition. Furthermore, these triflate groups contribute to the decoupling of Li+ and provide hopping sites for rapid Li+ transport, enabling a high room-temperature ionic conductivity of 1.1 mS cm-1 and a low activation energy of 0.17 eV, making it comparable to conventional liquid electrolytes. Consequently, Li symmetric cells using such SLE achieve extremely stable plating/stripping cycling over 3500 h at 0.5 mA cm-2 and support a high critical current up to 2 mA cm-2. The assembled Li||LiFePO4 solid-like batteries exhibit exceptional cyclability for over 1 year and a half, even outperforming liquid cells. Additionally, high-voltage cylindrical cells and high-capacity pouch cells are demonstrated, corroborating much simpler processibility in battery assembly compared to all-solid-state batteries.

Recent advances of antibacterial starch-based materials.

Starch has attracted a lot of attention because it is biodegradable, renewable, nontoxic and low cost. By adding antibacterial substances to starch, starch-based materials have antibacterial properties. The composite with other materials can improve the comprehensive performance of starch-based materials, thus broadening the application field of the material. In this paper, we focus on antibacterial starch-based materials and review their preparation and applications. It was found that antibacterial starch-based materials were most widely used in packaging, followed by medicine, and the research on smart starch-based materials was relatively less. This review may provide some reference value for subsequent studies of starch-based materials.

Reducing the Surface Tension of Zn Anodes by an Abietic Acid Layer for High Redox Kinetics and Reversibility.

Aqueous zinc batteries are appealing devices for cost-effective and environmentally sustainable energy storage. However, the critical issues of uncontrolled dendrite propagation and side reactions with Zn anodes have hindered their practical applications. Inspired by the functions of the rosin flux in soldering, an abietic acid (ABA) layer is fabricated on the surface of Zn anodes (ABA@Zn). The ABA layer protects the Zn anode from corrosion and the concomitant hydrogen evolution reaction. It also facilitates fast interfacial charge transfer and horizontal growth of the deposited Zn by reducing the surface tension of the Zn anode. Consequently, promoted redox kinetics and reversibility are simultaneously achieved by the ABA@Zn. It demonstrates stable Zn plating/stripping cycling over 5100 h and a high critical current of 8.0 mA cm-2. Moreover, the assembled ABA@Zn|(NH4)2V6O16 full cell delivers outstanding long-term cycling stability with an 89% capacity retention after 3000 cycles. This work provides a straightforward yet effective solution to the key issues of aqueous zinc batteries.

Preparation and Properties of Photoresponsive Pendimethalin@Silica-cinnamamide/γ-CD Microspheres for Pesticide Controlled Release.

Photocontrolled pesticide delivery systems have broad prospects for application in agriculture. Here, a novel photoresponsive herbicide delivery system was fabricated by functionalizing silica microsphere surfaces with cinnamamide and encapsulating the silica-cinnamamide with γ-cyclodextrin (γ-CD) to form a double-layered microsphere shell loaded with pendimethalin (pendimethalin@silica-cinnamamide/γ-CD). The microspheres showed remarkable loading capacity for pendimethalin (approximately 30.25% w/w) and displayed excellent photoresponsiveness and controlled release. The cumulative drug release rate exceeded 80% over 72 h under UV or sunlight irradiation. The herbicidal activity of the microspheres against Echinochloa crusgalli (L.) Beauv. was almost the same as that of pendimethalin under UV or sunlight. A bioactivity survey confirmed that the pendimethalin@silica-cinnamamide/γ-CD microspheres exhibited longer duration weed control than commercial pendimethalin. Allium cepa chromosomal aberration assays demonstrated that the microspheres showed lower genotoxicity than pendimethalin. These advantages indicate that pendimethalin@silica-cinnamamide/γ-CD microspheres constitute an environmentally friendly herbicidal formulation.

Nicotinamide restores tissue NAD+ and improves survival in rodent models of cardiac arrest.

Metabolic suppression in the ischemic heart is characterized by reduced levels of NAD+ and ATP. Since NAD+ is required for most metabolic processes that generate ATP, we hypothesized that nicotinamide restores ischemic tissue NAD+ and improves cardiac function in cardiomyocytes and isolated hearts, and enhances survival in a mouse model of cardiac arrest. Mouse cardiomyocytes were exposed to 30 min simulated ischemia and 90 min reperfusion. NAD+ content dropped 40% by the end of ischemia compared to pre-ischemia. Treatment with 100 µM nicotinamide (NAM) at the start of reperfusion completely restored the cellular level of NAD+ at 15 min of reperfusion. This rescue of NAD+ depletion was associated with improved contractile recovery as early as 10 min post-reperfusion. In a mouse model of cardiac arrest, 100 mg/kg NAM administered IV immediately after cardiopulmonary resuscitation resulted in 100% survival at 4 h as compared to 50% in the saline group. In an isolated rat heart model, the effect of NAM on cardiac function was measured for 20 min following 18 min global ischemia. Rate pressure product was reduced by 26% in the control group following arrest. Cardiac contractile function was completely recovered with NAM treatment given at the start of reperfusion. NAM restored tissue NAD+ and enhanced production of lactate and ATP, while reducing glucose diversion to sorbitol in the heart. We conclude that NAM can rapidly restore cardiac NAD+ following ischemia and enhance glycolysis and contractile recovery, with improved survival in a mouse model of cardiac arrest.

Miz1 promotes KRAS-driven lung tumorigenesis by repressing the protocadherin Pcdh10.

Targeting KRAS-mutated non-small-cell lung cancer (NSCLC) remains clinically challenging. Here we show that loss of function of Miz1 inhibits lung tumorigenesis in a mouse model of oncogenic KRAS-driven lung cancer. In vitro, knockout or silencing of Miz1 decreases cell proliferation, clonogenicity, migration, invasion, or anchorage-independent growth in mutant (MT) KRAS murine or human NSCLC cells but has unremarkable impact on non-tumorigenic cells or wild-type (WT) KRAS human NSCLC cells. RNA-sequencing reveals Protocadherin-10 (Pcdh10) as the top upregulated gene by Miz1 knockout in MT KRAS murine lung tumor cells. Chromatin immunoprecipitation shows Miz1 binding on the Pcdh10 promoter in MT KRAS lung tumor cells but not non-tumorigenic cells. Importantly, silencing of Pcdh10 rescues cell proliferation and clonogenicity in Miz1 knockout/knockdown MT KRAS murine or human tumor cells, and rescues allograft tumor growth of Miz1 knockout tumor cells in vivo. Miz1 is upregulated in MT KRAS lung tumor tissues compared with adjacent non-involved tissues in mice. Consistent with this, Miz1 is upregulated while Pcdh10 is downregulated in human lung adenocarcinomas (LUAD) compared with normal tissues, and high Miz1 levels or low Pcdh10 levels are associated with poor survival in lung cancer patients. Furthermore, the Miz1 signature is associated with worse survival in MT but not WT KRAS LUAD, and Pcdh10 is downregulated in MT compared to WT KRAS LUAD. Taken together, our studies implicate the Miz1/Pcdh10 axis in oncogenic KRAS-driven lung tumorigenesis.

Therapeutic hypothermia cardioprotection in murine hemorrhagic shock/resuscitation differentially affects p38α/p38γ, Akt, and HspB1.

BACKGROUND: Therapeutic hypothermia (TH) has demonstrated great potential for forestalling cardiovascular collapse and improving outcomes in the setting of severe hemorrhagic shock (HS). We used an established mouse model of severe HS to study the response of interrelated cardiac-signaling proteins p38, HspB1, and Akt to shock, resuscitation, and cardioprotective TH. METHODS: Adult female C57BL6/J mice were bled and maintained at a mean arterial pressure of 35 mm Hg. After 30 minutes, mice were randomized to 120 minutes of TH (33°C ± 0.5°C) or continued normothermia at 37°C. After 90 minutes, animals were resuscitated and monitored for 180 minutes. Cardiac p38, Akt, and HspB1 phosphorylation (p-p38, p-Akt, and p-HspB1), expression, and Akt/HspB1 interactions were measured at serial time points during HS and resuscitation. Markers of mitochondrial damage (plasma cytochrome c), inflammation (myeloperoxidase), and apoptosis (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling) were analyzed. RESULTS: By 15 minutes HS, p-p38 and p-HspB1 significantly increased while p-Akt(T308) decreased (p < 0.05). TH attenuated phosphorylation of the p38α isoform during HS and increased phosphorylation of the p38γ isoform during both HS and early resuscitation (p < 0.05). TH increased Akt/HspB1 coimmunoprecipitation during early resuscitation and increased p-Akt and HspB1 expression during late resuscitation (p < 0.05). Finally, TH attenuated the myocardial myeloperoxidase and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling staining and plasma cytochrome c during late resuscitation. CONCLUSIONS: TH increases phosphorylation of p38γ during both HS and early resuscitation, but attenuates phosphorylation of p38α, increases Akt/HspB1 interaction, and modulates Akt phosphorylation during HS and resuscitation. Such TH-related signaling events are associated with reduced cardiac inflammation, apoptosis, and mitochondrial injury.

Thermal properties and enzymatic degradation of PBS copolyesters containing dl-malic acid units.

A series of biodegradable copolyester of poly (butylene succinate-co-butylene malate) (P (BS-co-BM)) bearing hydroxyl groups were prepared by one-pot synthetic strategy without hydroxy-protection. The structure and properties of the P (BS-co-BM) were characterized by nuclear magnetic resonance (1H NMR), thermogravimetry analysis (TGA), differential scanning calorimetry (DSC), polarized optical microscope (POM), contact angle tester and enzymatic degradation. The results showed that the P (BS-co-BM) manifested excellent thermal properties. The glass transition temperature (Tg) of the P (BS-co-BM) increased with malic acid units added, the crystallizability temperature (Tc) decreased from 72.6 °C to 21.7 °C, and the melting point temperature (Tm) decreased from 117.9 °C to 82.4 °C. The crystallization rate of poly(butylene succinate) (PBS) segment within P (BS-co-BM) was improved by the introduction of malic acid. The enzymatic degradation rate increased with hydrophilicity of the copolyester improving.

Correction: Poly(adenine)-mediated DNA-functionalized gold nanoparticles for sensitive detection of mercury ions in aqueous media.

[This corrects the article DOI: 10.1039/C9RA03041G.].

Group V Phospholipase A2 Mediates Endothelial Dysfunction and Acute Lung Injury Caused by Methicillin-Resistant Staphylococcus Aureus.

Lung endothelial dysfunction is a key feature of acute lung injury (ALI) and clinical acute respiratory distress syndrome (ARDS). Previous studies have identified the lipid-generating enzyme, group V phospholipase A2 (gVPLA2), as a mediator of lung endothelial barrier disruption and inflammation. The current study aimed to determine the role of gVPLA2 in mediating lung endothelial responses to methicillin-resistant Staphylococcus aureus (MRSA, USA300 strain), a major cause of ALI/ARDS. In vitro studies assessed the effects of gVPLA2 inhibition on lung endothelial cell (EC) permeability after exposure to heat-killed (HK) MRSA. In vivo studies assessed the effects of intratracheal live or HK-MRSA on multiple indices of ALI in wild-type (WT) and gVPLA2-deficient (KO) mice. In vitro, HK-MRSA increased gVPLA2 expression and permeability in human lung EC. Inhibition of gVPLA2 with either the PLA2 inhibitor, LY311727, or with a specific monoclonal antibody, attenuated the barrier disruption caused by HK-MRSA. LY311727 also reduced HK-MRSA-induced permeability in mouse lung EC isolated from WT but not gVPLA2-KO mice. In vivo, live MRSA caused significantly less ALI in gVPLA2 KO mice compared to WT, findings confirmed by intravital microscopy assessment in HK-MRSA-treated mice. After targeted delivery of gVPLA2 plasmid to lung endothelium using ACE antibody-conjugated liposomes, MRSA-induced ALI was significantly increased in gVPLA2-KO mice, indicating that lung endothelial expression of gVPLA2 is critical in vivo. In summary, these results demonstrate an important role for gVPLA2 in mediating MRSA-induced lung EC permeability and ALI. Thus, gVPLA2 may represent a novel therapeutic target in ALI/ARDS caused by bacterial infection.

miR-221-5p-Mediated Downregulation of JNK2 Aggravates Acute Lung Injury.

Sepsis and acute lung injury (ALI) are linked to mitochondrial dysfunction; however, the underlying mechanism remains elusive. We previously reported that c-Jun N-terminal protein kinase 2 (JNK2) promotes stress-induced mitophagy by targeting small mitochondrial alternative reading frame (smARF) for ubiquitin-mediated proteasomal degradation, thereby preventing mitochondrial dysfunction and restraining inflammasome activation. Here we report that loss of JNK2 exacerbates lung inflammation and injury during sepsis and ALI in mice. JNK2 is downregulated in mice with endotoxic shock or ALI, concomitantly correlated inversely with disease severity. Small RNA sequencing revealed that miR-221-5p, which contains seed sequence matching to JNK2 mRNA 3' untranslated region (3'UTR), is upregulated in response to lipopolysaccharide, with dynamically inverse correlation with JNK2 mRNA levels. miR-221-5p targets the 3'UTR of JNK2 mRNA leading to its downregulation. Accordingly, miR-221-5p exacerbates lung inflammation and injury during sepsis in mice by targeting JNK2. Importantly, in patients with pneumonia in medical intensive care unit, JNK2 mRNA levels in alveolar macrophages flow sorted from non-bronchoscopic broncholaveolar lavage (BAL) fluid were inversely correlated strongly and significantly with the percentage of neutrophils, neutrophil and white blood cell counts in BAL fluid. Our data suggest that miR-221-5p targets JNK2 and thereby aggravates lung inflammation and injury during sepsis.

Poly(adenine)-mediated DNA-functionalized gold nanoparticles for sensitive detection of mercury ions in aqueous media.

In this work, a facile and sensitive colorimetric sensor for Hg2+ ions based on poly (adenine)-mediated DNA-functionalized gold nanoparticles (Au NPs) is reported. One DNA sequence consisting of poly-A and T-rich DNA was designed rationally. Poly-A was used as an anchoring block to bind tightly to Au NPs, and T-rich DNA was utilized for specific recognition of Hg2+ ions. With the assistance of poly-A, T-rich DNA was easily introduced onto the surface of Au NPs and kept an upright orientation. In the presence of Hg2+ ions, T base binding with Hg2+ ions results in the formation of "T-Hg2+-T" among the Au NPs, which caused aggregation of the Au NPs and a subsequent change in the color of the solution, from wine red to grayish blue. On this occasion, the limit of detection (LOD) was 3.75 nM Hg2+ ions with a linear range from 5 nM to 200 nM, as measured by UV-Vis spectroscopy. Moreover, successful application of this method for the detection of Hg2+ ions in real samples was demonstrated.