Platelet Exosome-Derived miR-223-3p Regulates Pyroptosis in the Cell Model of Sepsis-Induced Acute Renal Injury by Targeting Mediates NLRP3.

BACKGROUND: The present study investigated the roles and mechanisms of platelet-derived exosomes in sepsis-induced acute renal injury. METHODS: The blood samples of septic patients and healthy controls were collected for clinical examination. The plasma levels of miR-223-3p and NLRP3 mRNA were analyzed by qRT-PCR and the serum IL-1ß and creatinine levels were quantified by enzyme-linked immunosorbent assay (ELISA). C57BL/6 mice injected with LPS (lipopolysaccharide) were employed as the animal model for sepsis-induced acute renal injury. Human coronary artery endothelial cells (HCAECs) were treated with TNF-α as a cellular model for sepsis-induced endothelial damages. RESULTS: The number of PMP (platelet-derived microparticles) in patients with sepsis was increased. The level of miR-223-3p in the platelet exosomes isolated from the serum sample in patients with sepsis was significantly lower than that of the healthy controls. The level of miR-223-3p was also decreased in the platelet exosomes of mouse model with sepsis-induced acute renal injury. Downregulating miR-223-3p promoted sepsis-induced acute renal injury in mice model, while the administration of miR-223-3p reduced the inflammation in endothelial cells of sepsis-induced acute renal injury. NLRP3 (NLR Family Pyrin Domain Containing 3) was identified as one target of miR-223-3p in the platelet exosomes of sepsis-induced acute kidney injury. miR-223-3p attenuated NLRP3-induced pyroptosis in endothelial cell model of sepsis-induced acute kidney injury. CONCLUSION: Our data suggest that platelet exosome-derived miR-223-3p negatively regulates NLRP3-dependent inflammasome to suppress pyroptosis in endothelial cells. Decreased miR-223-3p expression promotes the inflammation in sepsis-induced acute renal injury. Targeting miR-223-3p may be developed into a therapeutic approach for sepsis-induced acute renal injury.

Combination of Ternary Electrochemiluminescence System of BNQDs/AgMOG-K2S2O8 and Electrochemiluminescence Resonance Energy Transfer Strategy for Ultrasensitive Immunoassay of Amyloid-ß Protein.

In this work, based on boron nitride quantum dots (BNQDs) as energy donors and MnO2@MWCNTs-COOH as energy receptors, we designed an efficient electrochemiluminescence resonance energy transfer (ECL-RET) immunosensor for the detection of amyloid-ß (Aß42) protein, a biomarker of Alzheimer's disease (AD). First, the signal amplification of a ternary ECL system composed of BNQDs (as the ECL emitter), K2S2O8 (as the coreactant), and silver metal-organic gels (AgMOG, as the coreaction accelerator) was realized, and PDDA as stabilizer was added, a strong and stable initial ECL signal was obtained. AgMOG could not only support a large amount of BNQDs and Aß42 capture antibody (Ab1) through Ag-N bond but also exhibit excellent ECL catalytic performance and enhance the luminescent intensity of BNQDs@PDDA-K2S2O8 system. In addition, due to the broad absorption spectrum of MnO2@MWCNTs-COOH and the extensive overlap with the ECL emission spectrum of BNQDs, the quenching probe Ab2-MnO2@MWCNTs-COOH could be introduced into the ternary system through a sandwich immune response. On this basis, the signal on-off ECL immunosensor was constructed to achieve the ultrasensitive detection of Aß42 through signal transformation. Under the optimal conditions, the prepared ECL biosensor manifested a wide linear range (10 fg/mL-100 ng/mL) with a detection limit of 2.89 fg/mL and showed excellent stability, selectivity, and repeatability, which provided an effective strategy for the ultrasensitive detection of biomarkers in clinical analysis.

Room-Temperature Synthesized Iron/Cobalt Metal-Organic Framework Nanosheets with Highly Efficient Catalytic Activity toward Luminol Chemiluminescence Reaction.

Two-dimensional (2D) iron/cobalt metal-organic framework nanosheets (Fe/Co-MOF NSs) were synthesized via the cooperative self-assembly reaction of Fe3+/Co2+ and terephthalic acid at room temperature. The as-prepared 2D Fe/Co-MOF NSs display superior performance in catalysis of the chemiluminescence (CL) reaction between luminol and H2O2. The CL spectrum, UV-vis absorption spectroscopy, radical scavenger experiments, and electron spin resonance (ESR) spectroscopy are utilized to research the possible CL mechanism of the luminol-H2O2-Fe/Co-MOF NSs system. All results indicate that Fe/Co-MOF NSs present outstanding peroxidase-like activity and could catalyze H2O2 to produce 1O2, O2·-, and ·OH, which could react rapidly with the luminol anion radical and result in strong CL. With the highly efficient CL of the luminol-H2O2-Fe/Co-MOF NSs system, a sensitive sensor for the detection of dopamine (DA) is developed based on the inhibitory effect of DA on the CL intensity. Good linearity over the range of 50-800 nM is achieved with a limit of detection of 20.88 nM (S/N = 3). This research demonstrates that 2D Fe/Co-MOF NSs is a highly effective catalyst for luminol CL reaction and has great application potential in the CL field.

Sensitive and Amplification-Free Electrochemiluminescence Biosensor for HPV-16 Detection Based on CRISPR/Cas12a and DNA Tetrahedron Nanostructures.

Rapid and accurate detection of biomarkers was very important for early screening and treatment of diseases. Herein, a sensitive and amplification-free electrochemiluminescence (ECL) biosensor based on CRISPR/Cas12a and DNA tetrahedron nanostructures (TDNs) was constructed. Briefly, 3D TDN was self-assembled on the Au nanoparticle-deposited glassy carbon electrode surface to construct the biosensing interface. The presence of the target would activate the trans-cleavage activity of Cas12a-crRNA duplex to cleave the single-stranded DNA signal probe on the vertex of TDN, causing the Ru(bpy)32+ to fall from the electrode surface and weakened the ECL signal. Thus, the CRISPR/Cas12a system transduced the change of target concentration into an ECL signal enabling the detection of HPV-16. The specific recognition of CRISPR/Cas12a to HPV-16 made the biosensor have good selectivity, while the TDN-modified sensing interface could reduce the cleaving steric resistance and improve the cleaving performance of CRISPR/Cas12a. In addition, the pretreated biosensor could complete sample detection within 100 min with a detection limit of 8.86 fM, indicating that the developed biosensor possesses the potential application prospect for fast and sensitive nucleic acid detection.

Responses of sediment nitrogen forms and bacterial communities to different aquatic nitrogen conditions in three submerged macrophyte-type ecological treatment systems.

Ecological treatment system (ETS) has been recognized as a promising technology for mitigating agricultural non-point pollution, whereas it remains to be seen how nitrogen (N) forms and bacterial communities in ETS sediments respond to different aquatic N conditions. Therefore, a four-month microcosm experiment was conducted to investigate the effects of three aquatic N conditions (2 mg/L NH4+-N, 2 mg/L NO3--N and 1 mg/L NH4+-N + 1 mg/L NO3--N) on sediment N forms and bacterial communities in three ETSs vegetated by Potamogeton malaianus, Vallisneria natans and artificial aquatic plant, respectively. Through analysis of four transferable N fractions, the valence states of N in ion-exchange and weak acid extractable fractions were found to be mainly determined by aquatic N conditions, while significant N accumulation was observed only in strong oxidant extractable and strong alkali extractable fractions. Sediment N profiles were primarily influenced by time and plant types, with N condition having secondary effect, while sediment bacterial community structures experienced a significant shift over time and were slightly influenced by plant types. Sediment functional genes related to N fixation, nitrification, assimilable nitrate reduction, dissimilatory nitrite reduction (DNRA) and denitrification were substantially enriched in month 4, and the bacterial co-occurrence network exhibited less complexity but more stability under NO3- condition compared to others. Furthermore, certain sediment N fractions were found to have strong relationships with specific sediment bacteria, such as nitrifiers, denitrifiers and DNRA bacteria. Our findings highlight the significant influence of aquatic N condition in submerged macrophyte-type ETSs on sediment N forms and bacterial communities.

Versatile Electrochemiluminescence Biosensing Platform Based on DNA Nanostructures and Catalytic Hairpin Assembly Signal Amplification.

Achieving rapid and highly sensitive detection of biomarkers is crucial for disease diagnosis and treatment. Here, a highly sensitive and versatile dual-amplification electrochemiluminescence (ECL) biosensing platform was constructed for target detection based on DNA nanostructures and catalyzed hairpin assembly (CHA). Specifically, when the target DNA was present, it would hybridize with the auxiliary strands (D1 and D2) to form an I-shaped nanostructure, which in turn triggered the subsequent catalytic hairpin assembly reaction to generate plenty of double-stranded DNA complexes (H1-H2). The resulting double-stranded complex could be trapped on the electrode surface and adsorbed the ECL signal probe Ru(phen)32+.We found that the I-shaped nanostructure-triggered CHA reaction had higher amplification efficiency compared with traditional CHA amplification. Thus, a sensitive "signal-on" ECL biosensor was constructed for target DNA detection with a detection limit of 1.09 fM. Additionally, by combining the binding properties of C-Ag+-C with an elaborately designed "Ag+-helper" probe, the proposed strategy could be immediately utilized for the highly sensitive and selective detection of silver ions, demonstrating the versatility of the developed biosensing platform. This strategy provided a new approach with potential applications in disease diagnosis and environmental monitoring.

Extra-pulmonary complications of 45 critically ill patients with COVID-19 in Yichang, Hubei province, China: A single-centered, retrospective, observation study.

ABSTRACT: Mortality of critically ill patients with coronavirus disease 2019 (COVID-19) was high. Aims to examine whether time from symptoms onset to intensive care unit (ICU) admission affects incidence of extra-pulmonary complications and prognosis in order to provide a new insight for reducing the mortality. A single-centered, retrospective, observational study investigated 45 critically ill patients with COVID-19 hospitalized in ICU of The Third People's Hospital of Yichang from January 17 to March 29, 2020. Patients were divided into 2 groups according to time from symptoms onset to ICU admission (>7 and ≤7 days) and into 2 groups according to prognosis (survivors and non-survivors). Epidemiological, clinical, laboratory, radiological characteristics and treatment data were studied. Compared with patients who admitted to the ICU since symptoms onset ≤7 days (55.6%), patients who admitted to the ICU since symptoms onset >7 days (44.4%) were more likely to have extra-pulmonary complications (19 [95.0%] vs 16 [64.0%], P = .034), including acute kidney injury, cardiac injury, acute heart failure, liver dysfunction, gastrointestinal hemorrhage, hyperamylasemia, and hypernatremia. The incidence rates of acute respiratory distress syndrome, pneumothorax, and hospital-acquired pneumonia had no difference between the 2 groups. Except activated partial thromboplastin and Na+ concentration, the laboratory findings were worse in group of time from symptoms onset to ICU admission >7 days. There was no difference in mortality between the 2 groups. Of the 45 cases in the ICU, 19 (42.2%) were non-survivors, and 16 (35.6%) were with hospital-acquired pneumonia. Among these non-survivors, hospital-acquired pneumonia was up to 12 (63.2%) besides higher incidence of extra-pulmonary complications. However, hospital-acquired pneumonia occurred in only 4 (15.4%) survivors. Critically ill patients with COVID-19 who admitted to ICU at once might get benefit from intensive care via lower rate of extra-pulmonary complications.

Zinc-finger protein 418 overexpression protects against cardiac hypertrophy and fibrosis.

BACKGROUND: This study aimed to investigated the effect and mechanism of zinc-finger protein 418 (ZNF418) on cardiac hypertrophy caused by aortic banding (AB), phenylephrine (PE) or angiotensin II (Ang II) in vivo and in vitro. METHODS: The expression of ZNF418 in hearts of patients with dilated cardiomyopathy (DCM) or hypertrophic cardiomyopathy (HCM) and AB-induced cardiac hypertrophy mice, as well as in Ang II- or PE-induced hypertrophic primary cardiomyocytes was detected by western blotting. Then, the expression of ZNF418 was up-regulated or down-regulated in AB-induced cardiac hypertrophy mice and Ang II -induced hypertrophic primary cardiomyocytes. The hypertrophic responses and fibrosis were evaluated by echocardiography and histological analysis. The mRNA levels of hypertrophy markers and fibrotic markers were detected by RT-qPCR. Furthermore, the phosphorylation and total levels of c-Jun were measured by western blotting. RESULTS: ZNF418 was markedly down-regulated in hearts of cardiac hypertrophy and hypertrophic primary cardiomyocytes. Down-regulated ZNF418 exacerbated the myocyte size and fibrosis, moreover increased the mRNA levels of ANP, BNP, ß-MHC, MCIP1.4, collagen 1a, collagen III, MMP-2 and fibronection in hearts of AB-treated ZNF418 knockout mice or Ang II-treated cardiomyocytes with AdshZNF418. Conversely, these hypertrophic responses were reduced in the ZNF418 transgenic (TG) mice treated by AB and the AdZNF418-transfected primary cardiomyocytes treated by Ang II. Additionally, the deficiency of ZNF418 enhanced the phosphorylation level of c-jun, and overexpression of ZNF418 suppressed the phosphorylation level of c-jun in vivo and in vitro. CONCLUSION: ZNF418 maybe attenuate hypertrophic responses by inhibiting the activity of c-jun/AP-1.

SOCS2 exacerbates myocardial injury induced by ischemia/reperfusion in diabetic mice and H9c2 cells through inhibiting the JAK-STAT-IGF-1 pathway.

AIMS: This study aimed to investigate potential candidates and molecular mechanisms of myocardial ischemia/reperfusion (I/R) injury (MIRI) in type 2 diabetes mellitus. MAIN METHODS: Type 2 diabetic and myocardial I/R mouse models were established with a high fat-diet (HFD) for 24weeks and subjecting to global ischemia/reperfusion for 1h/3h, respectively. Microarray analysis was applied to screen differentially expressed genes (DEGs) in the hearts of these mice. Moreover, H9c2 cells were treated with high glucose (HG) and/or hypoxia and reoxygenation (H/R). Subsequently, the expression of suppressor of cytokine signaling 2 (SOCS2) was knocked down by siRNA followed by the above treatments. Then, the cell lipid peroxidation and apoptosis-related indicators (malondialdehyde, MDA, and lactate dehydrogenase, LDH, cleaved-caspase-3; glucose-regulated protein 78, GRP78;), Janus kinase (JAK)/signal transducers and activators of transcription (STAT) signaling pathway-related proteins (p-JAK2 and p-STAT5b) and insulin-like growth factor-1 (IGF-1) were detected. KEY FINDINGS: The mRNA levels of selected DEGs, such as Angptl4, Gadd45b, Rnf122 and SOCS2, showed a high degree of correlation with the microarray data. In addition, the levels of SOCS2, caspase-3, GRP78, LDH and MDA were increased, while the IGF-1 level was down-regulated in cells treated with HG and/or H/R compared to untreated cells (p<0.05). However, SOCS2 knockdown elevated the expression levels of IGF-1, p-JAK2 and p-STAT5b, as well as caspase-3, GRP78, LDH and MDA. SIGNIFICANCE: This research suggests that overexpressed SOCS2 might exacerbates MIRI in type 2 diabetes mellitus by inhibiting the expression of IGF-1 via the JAK-STAT signaling pathway.