Pellino1 orchestrates gut-kidney axis to perpetuate septic acute kidney injury through activation of STING pathway and NLRP3 inflammasome.

AIMS: Intestinal barrier dysfunction is the initial and propagable factor of sepsis in which acute kidney injury (AKI) has been considered as a common life-threatening complication. Our recent study identifies the regulatory role of Pellino1 in tubular death under inflammatory conditions in vitro. The objective of our current study is to explore the impact of Pellino1 on gut-kidney axis during septic AKI and uncover the molecular mechanism (s) underlying this process. MATERIALS AND METHODS: Immunohistochemistry (IHC) was conducted to evaluate Pellino1 and NOD-like receptor thermal protein domain associated protein 3 (NLRP3) levels in renal biopsies from critically ill patients with a clinical diagnosis of sepsis. Functional and mechanistic studies were characterized in septic models of the Peli-knockout (Peli1-/-) mice by histopathological staining, enzyme-linked immunosorbent assay (ELISA), flow cytometry, immunofluorescence, biochemical detection, CRISPR/Cas9-mediated gene editing and intestinal organoid. KEY FINDINGS: Pellino1, together with NLRP3, are highly expressed in renal biopsies from critically ill patients diagnosed with sepsis and kidney tissues of septic mice. The Peli1-/- mice with sepsis become less prone to develop AKI and have markedly compromised NLRP3 activation in kidney. Loss of Peli1 endows septic mice refractory to intestinal inflammation, barrier permeability and enterocyte apoptosis that requires stimulator of interferons genes (STING) pathway. Administration of STING agonist DMXAA deteriorates AKI and mortality of septic Peli1-/- mice in the presence of kidney-specific NLRP3 reconstitution. SIGNIFICANCE: Our studies suggest that Pellino1 has a principal role in orchestrating gut homeostasis towards renal pathophysiology, thus providing a potential therapeutic target for septic AKI.

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 SIRPA in macrophages ameliorates AKI and systemic inflammation response in septic mice, accompanied by an escalation in mitophagy inhibition of macrophages. Ablation of SIRPA transcriptionally downregulates solute carrier family 22 member 5 (SLC22A5) in the lipopolysaccharide (LPS)-stimulated macrophages that efferocytose apoptotic neutrophils (PMNs). Targeting SLC22A5 renders mitophagy inhibition of macrophages in response to LPS stimuli, improves survival and deters development of septic AKI. Our study supports further clinical investigation of CD47-SIRPα signalling in sepsis and proposes that SLC22A5 might be a promising immunotherapeutic target for septic AKI.

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-Igfbp7em1Cd1165/Gpt mice subjected to cecal ligation and puncture (CLP). Transmission electron microscopy, immunofluorescence, flow cytometry, immunoblotting, ELISA, RT-qPCR and dual-luciferase reporter assays were used to determine mitochondrial functions, cell apoptosis, cytokine secretion and gene transcription. KEY FINDINGS: ICTD augments the transcriptional activity and protein secretion of tubular IGFBP-7, which enables an auto- and paracrine signalling via deactivation of IGF-1 receptor (IGF-1R). Genetic knockout (KO) of IGFBP-7 provides renal protection, improves survival and resolves inflammation in murine models of cecal ligation and puncture (CLP), while administering recombinant IGFBP-7 aggravates ICTD and inflammatory invasion. IGFBP-7 perpetuates ICTD in a NIX/BNIP3-indispensable fashion through dampening mitophagy that restricts redox robustness and preserves mitochondrial clearance programs. Adeno-associated viral vector 9 (AAV9)-NIX short hairpin RNA (shRNA) delivery ameliorates the anti-septic AKI phenotypes of IGFBP-7 KO. Activation of BNIP3-mediated mitophagy by mitochonic acid-5 (MA-5) effectively attenuates the IGFBP-7-dependent ICTD and septic AKI in CLP mice. SIGNIFICANCE: Our findings identify IGFBP-7 is an auto- and paracrine manipulator of NIX-mediated mitophagy for ICTD escalation and propose that targeting the IGFBP-7-dependent ICTD represents a novel therapeutic strategy against septic AKI.

Effects of Low Nighttime Temperature on Fatty Acid Content in Developing Seeds from Brassica napus L. Based on RNA-Seq and Metabolome.

Brassica napus L. is a vital plant oil resource worldwide. The fatty acid biosynthesis and oil accumulation in its seeds are controlled by several genetic and environmental factors, including daytime and nighttime temperatures. We analyzed changes in oleic and erucic acid content in two double haploid (DH) lines, DH0729, a weakly temperature-sensitive line, and DH0815, a strongly temperature-sensitive line, derived from B. napus plants grown at different altitudes (1600, 1800, 2000, 2200, and 2400 m a.s.l., 28.85° N, 112.35° E) and nighttime temperatures (20/18, 20/16, 20/13 and 20/10 °C, daytime/nighttime temperature). Based on medium- and long-chain fatty acid metabolites, the total oleic acid content 35 and 43 days after flowering was significantly lower in low nighttime temperature (LNT, 20/13 °C) plants than in high nighttime temperature (HNT, 20/18 °C) plants (HNT: 58-62%; LNT: 49-54%; an average decrease of 9%), and the total erucic acid content was significantly lower in HNT than in LNT plants (HNT: 1-2%; LNT: 8-13%; an average increase of 10%). An RNA-seq analysis showed that the expression levels of SAD (LOC106366808), ECR (LOC106396280), KCS (LOC106419344), KAR (LOC106367337), HB1(LOC106430193), and DOF5 (LOC111211868) in STSL seeds increased under LNT conditions. In STSL seeds, a base mutation in the cis-acting element involved in low-temperature responsiveness (LTR), the HB1 and KCS promoter caused loss of sensitivity to low temperatures, whereas that of the KCS promoter caused increased sensitivity to low temperatures.

Deep Bidirectional Recurrent Neural Networks Ensemble for Remaining Useful Life Prediction of Aircraft Engine.

Remaining useful life (RUL) prediction of aircraft engine (AE) is of great importance to improve its reliability and availability, and reduce its maintenance costs. This article proposes a novel deep bidirectional recurrent neural networks (DBRNNs) ensemble method for the RUL prediction of the AEs. In this method, several kinds of DBRNNs with different neuron structures are built to extract hidden features from sensory data. A new customized loss function is designed to evaluate the performance of the DBRNNs, and a series of the RUL values is obtained. Then, these RUL values are reencapsulated into a predicted RUL domain. By updating the weights of elements in the domain, multiple regression decision tree (RDT) models are trained iteratively. These models integrate the predicted results of different DBRNNs to realize the final RUL prognostics with high accuracy. The proposed method is validated by using C-MAPSS datasets from NASA. The experimental results show that the proposed method has achieved more superior performance compared with other existing methods.

Chemical constituents, biological activities and anti-rheumatoid arthritic properties of four citrus essential oils.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease with predominant synovitis that has no complete cure or preventive treatment. Citrus essential oils, used in natural fragrances, contain a variety of functional ingredients that are worthy of investigation for their potential as natural anti-inflammatory drug sources. In this study, essential oils were hydro distilled from the peels of four citrus species: Citrus sinensis (L.) Osbeck (CSEOs), Citrus paradisi Macfad. (CPEOs), Citrus limon (L.) Osbeck (CLEOs) and Citri Reticulatae Pericarpium (CREOs). Altogether, 81 compounds were identified using gas chromatography-mass spectrometry (GC-MS), of which d-limonene (17.96%-94.66%) was an abundant component of all four oils. The stable 1,1-diphenyl-2-pyrrole hydrazine (DPPH) free radical test showed that all four essential oils had excellent antioxidant properties (IC50 , 0.76-13.86 µg/mL). Furthermore, the oils remarkably increased the first G1 phase of the cell cycle, which inhibited the pro-inflammatory factor expression. An immunohistochemical analysis indicated that the four essential oils inhibited the expression of tumor necrosis factor-α and cyclooxygenase-2 and they exhibited anti-inflammatory activity in a rat model that was similar to that of the common drug, Ibuprofen. These results show that the CSEOs, CPEOs, CLEOs, and CREOs have significant antirheumatic activities and thus have great potential in developing functional food or drugs for treating RA.

Erratum: Role of Sirolimus in renal tubular apoptosis in response to unilateral ureteral obstruction: Erratum.

[This corrects the article DOI: 10.7150/ijms.26954.].

Loss of EphA7 Expression in Basal Cell Carcinoma by Hypermethylation of CpG Islands in the Promoter Region.

Basal cell carcinoma (BCC) is the most common malignancy worldwide, with increasing incidence. BCCs present low mortality but high morbidity, and its pathogenesis remains unclear. Eph receptors have been implicated in tumorigenesis. EphA7 plays a role as a tumor suppressor in certain cancers. We checked EphA7 expression levels and methylation status in a set of BCCs, benign skin diseases, and compound nevus tissue samples using immunohistochemistry. EphA7 protein was positively expressed in normal basal cells, benign skin diseases, and compound nevus cells, but lost in areas of BCC tissues. We detected hypermethylation in BCC tissue samples with reduced expression of EphA7. There is a significant relationship between the expression level of EphA7 receptor protein and the methylation status of CpG islands in the EphA7 promoter region (P < 0.001). To our knowledge, this is the first study to report the EphA7 expression profile and hypermethylation of EphA7 in BCC. The role of the EphA7 gene and the status of hypermethylation in tumorigenesis and treatment of BCC warrant further investigation.

Convolutional Ordinal Regression Forest for Image Ordinal Estimation.

Image ordinal estimation is to predict the ordinal label of a given image, which can be categorized as an ordinal regression (OR) problem. Recent methods formulate an OR problem as a series of binary classification problems. Such methods cannot ensure that the global ordinal relationship is preserved since the relationships among different binary classifiers are neglected. We propose a novel OR approach, termed convolutional OR forest (CORF), for image ordinal estimation, which can integrate OR and differentiable decision trees with a convolutional neural network for obtaining precise and stable global ordinal relationships. The advantages of the proposed CORF are twofold. First, instead of learning a series of binary classifiers independently, the proposed method aims at learning an ordinal distribution for OR by optimizing those binary classifiers simultaneously. Second, the differentiable decision trees in the proposed CORF can be trained together with the ordinal distribution in an end-to-end manner. The effectiveness of the proposed CORF is verified on two image ordinal estimation tasks, i.e., facial age estimation and image esthetic assessment, showing significant improvements and better stability over the state-of-the-art OR methods.

Liraglutide via Activation of AMP-Activated Protein Kinase-Hypoxia Inducible Factor-1α-Heme Oxygenase-1 Signaling Promotes Wound Healing by Preventing Endothelial Dysfunction in Diabetic Mice.

Background/Aims: Diabetic foot ulcers (DFUs) present a major challenge in clinical practice, and hyperglycemia-induced angiogenesis disturbance and endothelial dysfunction likely exacerbate DFUs. The long-acting glucagon-like peptide-1 (GLP-1) analog liraglutide (Lira) is a potential activator of AMP-activated protein kinase (AMPK) that appears to enhance endothelial function and have substantial pro-angiogenesis and antioxidant stress effects. Therefore, in this study, we aimed to investigate whether the protective role of Lira in diabetic wound healing acts against the mechanisms underlying hyperglycemia-induced endothelial dysfunction and angiogenesis disturbance. Methods: Accordingly, db/db mice were assessed after receiving subcutaneous Lira injections. We also cultured human umbilical vein endothelial cells (HUVECs) in either normal or high glucose (5.5 or 33 mM glucose, respectively) medium with or without Lira for 72 h. Results: An obvious inhibition of hyperglycemia-triggered endothelial dysfunction and angiogenesis disturbance was observed; follow by a promotion of diabetic wound healing under Lira treatment combined with restored hyperglycemia-impaired AMPK signaling pathway activity. AMPKα1/2 siRNA and Compound C (Cpd C), an inhibitor of AMPK, abolished both Lira-mediated endothelial protection and pro-angiogenesis action, as well as the diabetic wound healing promoted by Lira. Furthermore, hypoxia inducible factor-1α (Hif-1α; transcription factors of AMPK substrates) knockdown in HUVECs and db/db mice demonstrated that Lira activated AMPK to prevent hyperglycemia-triggered endothelial dysfunction and angiogenesis disturbance, with a subsequent promotion of diabetic wound healing that was Hif-1α-heme oxygenase-1 (HO-1) axis-dependent. Taken together, these findings reveal that the promotion of diabetic wound healing by Lira occurs via its AMPK-dependent endothelial protection and pro-angiogenic effects, which are regulated by the Hif-1α-HO-1 axis.

Caspase-1-Inhibitor AC-YVAD-CMK Inhibits Pyroptosis and Ameliorates Acute Kidney Injury in a Model of Sepsis.

OBJECTIVE: To observe the protective effect of AC-YVAD-CMK on sepsis-induced acute kidney injury in mice and to explore its possible mechanisms primarily. METHODS: Eighteen male C57BL/6 mice were randomly divided into sham-operated group (Control), cecal ligation and puncture group (CLP), and CLP model treated with AC-YVAD-CMK group (AC-YVAD-CMK) (n = 6 in each group). Mice were sacrificed at 24 h after operation, and blood and kidney tissue samples were collected for analyses. Histologic changes were determined microscopically following HE staining. The expression of Ly-6B and CD68 was investigated using immunohistochemistry. Serum concentrations of creatinine (sCR) and blood urea nitrogen (BUN) were measured. Serum levels of interleukin-1ß (IL-1ß), interleukin-18 (IL-18), TNF-α, and interleukin-6 (IL-6) were determined by ELISA. The expressions of Caspas-1, NLRP-1, IL-1ß, and IL-18 in renal tissues were investigated using Western blot. Immunofluorescence staining was used to detect the expression of GSDMD protein in renal tissues. RESULTS: AC-YVAD-CMK treatment significantly alleviates sepsis-induced acute kidney injury, with decreased histological injury in renal tissues, suppresses the accumulation of neutrophils and macrophages in renal tissues, and decreased sCR and BUN level (P < 0.05). Attenuation of sepsis-induced acute kidney injury was due to the prohibited production of inflammatory cytokines and decrease expression of Caspas-1, NLRP-1, IL-1ß, and IL-18 in renal tissues. In addition, AC-YVAD-CMK treatment significantly reduced the expression of GSDMD in renal tissues compared to those observed in controls (P < 0.05). CONCLUSIONS: We demonstrated a marked renoprotective effect of caspase-1-inhibitor AC-YVAD-CMK in a rat model of sepsis by inhibition of pyroptosis.

Randomized trial of the application value of comprehensive nursing intervention in the perioperative period of ruptured bleeding of ectopic pregnancy.

BACKGROUND: The purpose of this study was to explore the value of comprehensive nursing intervention in the perioperative period of ruptured bleeding of ectopic pregnancy. METHODS: From January 2015 to January 2020, 164 patients with rupture and bleeding of ectopic pregnancy who needed laparoscopic treatment in the department of gynecology at our hospital were selected and randomly divided into the basic nursing group and the comprehensive nursing group, with 82 cases each. During the perioperative period, comprehensive nursing intervention or basic nursing intervention were performed, and the nursing effects of the two nursing interventions were compared. RESULTS: The disappearance time of abdominal pain, the time to get out of bed, and the length of hospitalization in the comprehensive nursing group were significantly shorter than those in the basic nursing group (P<0.05). After surgery, blood sugar levels, aldosterone, cortisol, C-reactive protein (CRP), and IL-6 in the two groups were significantly higher than those before surgery (P<0.05), but there was no statistically significant difference between the groups (P>0.05). After the operation, the proportion of patients with Visual Analogue Scale (VAS) scores of 7-10 in the comprehensive nursing group was significantly lower than that in the basic nursing group (P<0.05). Before the intervention, the Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD) scores of the two groups were compared, and the difference was not statistically significant (P>0.05). After the intervention, the HAMA and HAMD scores of the comprehensive nursing group were significantly lower than those of the basic nursing group (P<0.05). The fallopian tube recanalization rate of patients in the comprehensive care group was significantly higher than that of the basic care group (P<0.05), and the complication rate was significantly lower than that of the basic care group (P<0.05). CONCLUSIONS: In summary, a comprehensive nursing program during the perioperative period can improve the treatment effect and significantly shorten the recovery time of patients, which is worthy of clinical promotion.

Development and Validation of a 5-Gene Autophagy-Based Prognostic Index in Endometrial Carcinoma.

BACKGROUND Endometrial carcinoma (EC) is the most common gynecological malignancy worldwide, and 15-20% of patients with EC have a rapid relapse within 3 years. This study aims to develop an autophagy-related genes (ARGs) signature to predict the prognosis of EC. MATERIAL AND METHODS In our study, differentially expressed ARGs were identified by "edgeR" package in R and pathway enrichment analysis was performed to explore biological functions. Univariate and multivariate Cox regression analyses were employed to build autophagy signature. Gene set enrichment analysis (GSEA), Kaplan-Meier curve analysis, and ROC curve analysis were conducted to compare the differences between the high- and low-risk groups. RESULTS A total of 60 differentially expressed ARGs (DEARGs) including 34 upregulated and 26 downregulated DEARGs were identified from the TCGAUCEC dataset, with the adjusted P<0.05 and |Fold Change| >1.5. By using univariate and multivariate Cox regression analyses, ERBB2, PRKAB2, GRID2, NRG3, CDKN2A were identified to construct a prognostic signature with AUC 0.673, 0.719, and 0.791, at 1-, 3- and 5- years, respectively. Patients with EC were divided into low- or high-risk group by median risk score, and GSEA showed that low-risk group was enriched in adjacent cells communication pathways while high-risk group was involved in metabolism and immune pathways. The nomograms could also help to guide personal prognostic prediction and therapeutic strategies in EC. CONCLUSIONS Our study not only determine 5 ARGs signature that could predict the prognosis of EC but also provide novel insights into the underlying mechanisms of autophagy.

Effects on the Ocular Surface from Reading on Different Smartphone Screens: A Prospective Randomized Controlled Study.

The purpose of this study was to investigate the influence of smartphone reading on the ocular surface and to compare the various effects of different screens and light conditions on the ocular surface. One hundred nineteen volunteers were randomly divided into: light + organic light-emitting diode (OLED), light + electronic ink (eINK), dark + OLED, and dark + eINK. Ocular surface examinations, including noninvasive break-up time (NIBUT), noninvasive keratograph tear meniscus height (NIKTMH), ocular redness, fluorescein break-up time (FBUT), corneal fluorescein staining, meibomian gland assessment, Schirmer I Test, and blinking frequency, were performed before and after a reading task. Symptoms were evaluated using the Ocular Surface Disease Index (OSDI) and Computer Vision Syndrome Questionnaire (CVS-Q). NIBUT and FBUT were decreased statistically significantly after participants read on an OLED screen for 2 hours compared with the baseline in light and dark environments, whereas no statistically significant decrease was observed on an eINK screen. NIKTMH was statistically significantly decreased after reading on an OLED screen in light and dark settings, and the eINK screen had a lesser effect on NIKTMH. An obvious increase in the ocular redness, OSDI and CVS-Q scores was observed after reading on an OLED screen, whereas the eINK screen had a lesser effect on these indicators. Blink rate increased gradually in OLED subgroups during the reading task, whereas no statistically significant difference was observed in the eINK subgroups. Our research suggested that reading on an OLED screen can cause ocular surface disorder and obvious subjective discomfort, whereas reading on an eINK screen can minimize ocular surface disorder in both dark and light environments.

A New Interaction Force Model of Gold Nanorods Derived by Molecular Dynamics Simulation.

Interactions between nanoparticles is one of the key factors governing their assembly for ordered structures. Understanding such interactions between non-spherical nanoparticles and developing a quantitative force model are critical to achieving the ordered structures for various applications. In the present study, the non-contact interactions of two identical gold nanorods (AuNRs) with different aspect ratios have been studied by molecular dynamics simulation. A new interaction potential and force model for two nanorods approaching side-by-side has been proposed as a function of particle surface separation and their relative orientation. In addition, the interaction potentials of two nanorods approaching in other typical orientation configurations (i.e., crossed, head-to-head and head-to-side) have also been investigated.

miR-34b-3p protects against acute kidney injury in sepsis mice via targeting ubiquitin-like protein 4A.

MicroRNAs (miRNAs) have been reported as a diagnostic markers for sepsis, and miRNAs have also been found to play a regulatory role in sepsis-induced acute kidney injury (AKI). However, the regulatory effect and mechanism of miR-34b-3p on AKI remains elusive. First, sepsis mice with AKI was established via cecal ligation puncture (CLP), and verified through hematoxylin-eosin staining, determination of tumor necrosis factor-α (TNF-α), interleukin (IL)-6/1ß and serum levels of alanine aminotransferase (ALT) and blood urea nitrogen (BUN). Data showed that CLP-induced mice demonstrated increased ALT, BUN, TNF-α, IL-1ß, and IL-6 with injured pathological morphology of kidney tissues. Second, lipopolysaccharide (LPS) treatment elevated TNF-α, IL-1ß, and IL-6 contents in rat mesangial cells (RMCs). MiR-34b-3p was downregulated in both CLP-induced mice and LPS-induced RMCs. Third, target gene of miR-34b-3p was verified as ubiquitin-like protein 4A (UBL4A), and UBL4A was upregulated in LPS-induced RMCs. MiR-34b-3p could inhibit UBL4A expression and decreased TNF-α, IL-1ß and IL-6 contents in LPS-induced RMCs, while overexpression of UBL4A counteract with the suppressive effects of miR-34b-3p on the protein expression. Moreover, transcriptional activity of UBL4A-induced NF-κB was decreased by miR-34b-3p. Lastly, in vivo injection of miR-34b-3p agomir improved CLP-induced kidney tissues injury with declined ALT, BUN, TNF-α, IL-1ß, IL-6, and UBL4A. In general, miR-34b-3p overexpression could alleviate AKI in sepsis mice through downregulation of UBL4A/NF-κB, providing potential therapeutic strategy for AKI.

Enhanced Microwave Absorption Bandwidth in Graphene-Encapsulated Iron Nanoparticles with Core-Shell Structure.

Graphene-encapsulated iron nanoparticles (Fe(G)) hold great promise as microwave absorbers owing to the combined dielectric loss of the graphene shell and the magnetic loss of the ferromagnetic metal core. Transmission electron microscopy (TEM) revealed transition metal nanoparticles encapsulated by graphene layers. The microwave electromagnetic parameters and reflection loss (R) of the Fe(G) were investigated. Graphene provided Fe(G) with a distinctive dielectric behavior via interfacial polarizations taking place at the interface between the iron cores and the graphene shells. The R of Fe(G)/paraffin composites with different Fe(G) contents and coating thickness was simulated according to the transmit-line theory and the measured complex permittivity and permeability. The Fe(G)/paraffin composites showed an excellent microwave absorption with a minimum calculated R of -58 dB at 11 GHz and a 60 wt% Fe(G) loading. The composites showed a wide bandwidth (the bandwidth of less than -10 dB was about 11 GHz). The R of composites with 1-3 mm coating thickness was measured using the Arch method. The absorption position was in line with the calculated results, suggesting that the graphene-coated iron nanoparticles can generate a suitable electromagnetic match and provide an intense microwave absorption. Excellent Fe(G) microwave absorbers can be obtained by selecting optimum layer numbers and Fe(G) loadings in the composites.

Regulatory mechanism of NOV/CCN3 in the inflammation and apoptosis of lung epithelial alveolar cells upon lipopolysaccharide stimulation.

Lipopolysaccharide (LPS) induces stress inflammation and apoptosis. Pulmonary epithelial cell apoptosis, which accelerates the progression of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), is the leading cause of mortality in patients with ALI/ARDS. The nephroblastoma overexpressed protein (CCN3), an inflammatory modulator, is reported to be a biomarker in ALI. Using the LPS-induced ALI model, this study investigated the expression of CCN3 and its possible molecular mechanism in lung alveolar epithelial cell inflammation and apoptosis. Our data revealed that LPS treatment greatly increased the level of CCN3 in A549 cells. The A549 cells were transfected with specific CCN3 small interfering RNA (siRNA) using transfection reagent. CCN3 siRNA not only largely attenuated the expressions of the inflammatory cytokines interleukin (IL)-1ß and transforming growth factor (TGF)-ß1, but also reduced the apoptotic rate of the AEC II cells and affected the expressions of the apoptosis-associated proteins (Bcl-2 and caspase-3). Furthermore, CCN3 knockdown greatly inhibited the activation of nuclear factor-κB p65 in A549 cells. In addition, TGF-ß/p-Smad inhibitor (TP0427736) and NF-κB inhibitor (PDTC) significantly attenuated the expression level of CCN3 in A549 cells. In conclusion, our data indicated that CCN3 siRNA affected downstream signal through TGF-ß/ p-Smad or NF-κB pathway, leading to the inhibition of cell inflammation and apoptosis in human alveolar epithelial cells.

Data-driven remaining useful life prediction via multiple sensor signals and deep long short-term memory neural network.

Remaining useful life (RUL) prediction is very important for improving the availability of a system and reducing its life cycle cost. This paper proposes a deep long short-term memory (DLSTM) network-based RUL prediction method using multiple sensor time series signals. The DLSTM model fuses multi-sensor monitoring signals for accurate RUL prediction, which is able to discover the hidden long-term dependencies among sensor time series signals through deep learning structure. By grid search strategy, the network structure and parameters of the DLSTM are efficiently tuned using an adaptive moment estimation algorithm so as to realize an accurate and robust prediction. Two various turbofan engine datasets are adopted to verify the performance of the DLSTM model. The experimental results demonstrate that the DLSTM model has a competitive performance in comparison with state-of-the-arts reported in literatures and other neural network models.