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Recent clinical research has revealed that mechanical ventilation (MV) can initiate pulmonary fibrosis and induce mechanical ventilation-induced pulmonary fibrosis (MVPF). However, the underlying mechanism remains largely uncharacterized. Based on a mouse model of MVPF and an alveolar epithelial cell cyclic strain model, the present study explores the possible mechanism of MVPF. Single-cell RNA-sequencing and EV RNA-sequencing analysis revealed that MV promoted apoptosis signal-regulating kinase 1 (ASK1)-mediated endoplasmic reticulum (ER) stress pathway activation and extracellular vesicle (EV) release from alveolar epithelial cells. Furthermore, the ASK1-ER stress pathway was shown to mediate mechanical stretch (MS)- or MV-induced EV release and lung fibroblast activation in vivo and in vitro. These processes were suppressed by ER stress inhibitors or by silencing ASK1 with ASK1- short hairpin RNA (shRNA). In addition, MVPF was suppressed by inhibiting ASK1 and ER stress in vivo. Therefore, the present study demonstrates that ASK1-ER stress pathway-mediated fibrotic-EV release from alveolar epithelial cells contributes to fibroblast activation and the initiation of pulmonary fibrosis during MV. The inhibited release of EVs targeting the ASK1-ER stress pathway might be a promising treatment strategy for MVPF.

Recent evidence has shown that lipopolysaccharide (LPS)-induced aerobic glycolysis of lung fibroblasts is closely associated with the pathogenesis of septic pulmonary fibrosis. Nevertheless, the underlying mechanism remains poorly defined. In this study, we demonstrate that LPS promotes c-Jun N-terminal kinase (JNK) signaling pathway activation and endogenous tumor necrosis factor-α (TNF-α) secretion in pulmonary macrophages. This, in turn, could significantly promote aerobic glycolysis and increase lactate production in lung fibroblasts through 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3 (PFKFB3) activation. Culturing human lung fibroblast MRC-5 cell line with TNF-α or endogenous TNF-α (cell supernatants of macrophages after LPS stimulation) both enhanced the aerobic glycolysis and increased lactate production. These effects could be prevented by treating macrophages with JNK pathway inhibitor, by administering TNF-α receptor 1 (TNFR1) siRNA, PFKFB3 inhibitor, or by silencing PFKFB3 with fibroblasts-specific shRNA. In addition, the inhibition of TNF-α secretion and PFKFB3 expression prevented LPS-induced pulmonary fibrosis in vivo. In conclusion, this study revealed that LPS-induced macrophage secretion of TNF-α could initiate fibroblast aerobic glycolysis and lactate production, implying that inflammation-metabolism interactions between lung macrophages and fibroblasts might play an essential role in LPS-induced pulmonary fibrosis.

In this article, an iterative learning algorithm based on extended state observer (ESO) is proposed to deal with the propeller failure of an underwater vehicle. In this control scheme, the nonlinear feedback mechanism of ESO is transplanted to iterative learning processes; that is, the nonlinear function of the current output residual is used to adjust the value of the virtual fault in the next iteration. Additionally, to ensure the safety of the control torque, a saturated proportional-derivative (PD) controller is proposed. Finally, to achieve online parameter self-tuning, a fuzzy logic controller is employed in this control scheme to fuzzify the parameters of a saturated PD controller and ESO. The obtained results show the favorable speed of tracking convergence and the high precision of fault estimation.

The leakage of hazardous gases poses a significant threat to public security and causes environmental damage. The effective and accurate source term estimation (STE) is necessary when a leakage accident occurs. However, most research generally assumes that no obstacles exist near the leak source, which is inappropriate in practical applications. To solve this problem, we propose two different frameworks to emphasize STE with obstacles based on artificial neural network (ANN) and convolutional neural network (CNN). Firstly, we build a CFD model to simulate the gas diffusion in obstacle scenarios and construct a benchmark dataset. Secondly, we define the structure of ANN by searching, then predict the concentration distribution of gas using the searched model, and optimize source term parameters by particle swarm optimization (PSO) with well-performed cost functions. Thirdly, we propose a one-step STE method based on CNN, which establishes a link between the concentration distribution and the location of obstacles. Finally, we propose a novel data processing method to process sensor data, which maps the concentration information into feature channels. The comprehensive experiments illustrate the performance and efficiency of the proposed methods.

Background We aimed to investigate the prevalence of poor uncorrected visual acuity and the difference among students with different ages and residential areas in the Northeast of China. The relationships between screen time, nighttime sleep duration, and poor uncorrected visual acuity would be explored. Methods It was a cross-sectional study using multi-stage stratified random sampling method to recruit participants. 2149 students have completed questionnaires and underwent visual acuity examinations. The dose–response curve method was applied to examine the non-linear associations between sleep duration and poor uncorrected visual acuity under different screen time subgroups. Results The overall prevalence of poor uncorrected visual acuity and severe poor uncorrected visual acuity was 84.7% and 63.3%, respectively. The dose–response curve showed the odds ratios (ORs) of sleep duration for the poor uncorrected visual increased relatively slowly when screen time Conclusion We found associations between nighttime sleep duration and poor uncorrected visual acuity in adolescents. However, these associations were not consistent across all screen time categories.

With rapid urbanisation, a karst water recharge area of the Jinan spring catchment was damaged. Thus, managed aquifer recharge projects were built in the western Jinan spring catchment to protect the water supply of the spring. Yufuhe River was selected as the study area to compute the effective recharge rate into karst aquifers. This strong seepage zone has a large gradient and undergoes a specific hydrogeological condition in which two strata of a gravel layer and limestone change to three strata of gravel, impermeable clay shale and limestone at the open window of the karst aquifers. A hydraulic model called HEC-RAS was applied to simulate the river stage, and a numerical groundwater model called HYDRUS-3D was adopted to simulate the groundwater mound dynamics and estimate river flow seepage into the aquifers. The effective recharge rates are 64.9%, 65.2% and 68.1% when the buried depths of groundwater are 40, 30 and 25 m. An analysis of the electric conductivity, water table, temperature and water volume data found an effective recharge rate of 68.3%. Results of field monitoring confirmed the accuracy of the numerical simulation and showed that most of the recharged water in the study reach can be effectively recharged into the karst aquifers.

Lipopolysaccharide (LPS)-induced autophagy inhibition in lung fibroblasts is closely associated with the activation of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K-Akt-mTOR) pathway. However, the underlying mechanism remains unknown. In this study, we demonstrated that LPS activated the PI3K-Akt-mTOR pathway and inhibited lung fibroblast autophagy by depleting thymocyte differentiation antigen-1 (Thy-1) and upregulating integrin β3 (Itgb3). Challenge of the human lung fibroblast MRC-5 cell line with LPS resulted in significant upregulation of integrin β3, activation of the PI3K-Akt-mTOR pathway and inhibition of autophagy, which could be abolished by integrin β3 silencing by specific shRNA or treatment with the integrin β3 inhibitor cilengitide. Meanwhile, LPS could inhibit Thy-1 expression accompanied with PI3K-Akt-mTOR pathway activation and lung fibroblast autophagy inhibition; these effects could be prevented by Thy-1 overexpression. Meanwhile, Thy-1 downregulation with Thy-1 shRNA could mimic the effects of LPS, inducing the activation of PI3K-Akt-mTOR pathway and inhibiting lung fibroblast autophagy. Furthermore, protein immunoprecipitation analysis demonstrated that LPS reduced the binding of Thy-1 to integrin β3. Thy-1 downregulation, integrin β3 upregulation and autophagy inhibition were also detected in a mouse model of LPS-induced pulmonary fibrosis, which could be prohibited by intratracheal injection of Thy-1 overexpressing adeno-associated virus (AAV) or intraperitoneal injection of the integrin β3 inhibitor cilengitide. In conclusion, this study demonstrated that Thy-1 depletion and integrin β3 upregulation are involved in LPS-induced pulmonary fibrosis, and may serve as potential therapeutic targets for pulmonary fibrosis., This study confirms that the depletion of Thy-1 and upregulation of integrin β3 is an essential mechanism and potential therapeutic target for PI3K-Akt-mTOR pathway-associated inhibition of lung fibroblast autophagy in lipopolysaccharide-induced pulmonary fibrosis.

To deal with the fault of the thrusters of AUV, an iterative learning algorithm based on the extended states observer (ESO) is established. In this algorithm, the nonlinear feedback mechanism of the ESO is transplanted to iterative learning processes, that is, the nonlinear function of the current output residual is used to adjust the value of the virtual fault in the next iteration. The obtained result shows the favorable convergence speed and the fault estimation precision of the proposed method.

To evaluate the plasma levels and clearance of procalcitonin (PCTc) as prognostic biomarkers for patients with abdominal sepsis. A retrospective study of 103 patients with abdominal sepsis was conducted in our intensive care unit (ICU) from 2016 to 2018. Procalcitonin (PCT) plasma levels were measured at the time of diagnosis of abdominal sepsis and daily over the next 5 days. PCTc was calculated from day 3 to day 5. The prognostic accuracy of PCTc was expressed as the area under the receiver operating characteristic curve (AUROC). The Kaplan–Meier method was used to compare the survival curves by log-rank test. Logistic regression analysis was used to predict the 28-day mortality. The primary outcome was 28-day mortality since admission to ICU. Serum PCT levels from day 1 to day 5 did not differ significantly between survivors and non-survivors, while PCTc on day 5 was statistically significantly higher in survivors than that in non-survivors (86.4% vs 38.7%, P 70% compared with those with PCTc-day 5

During cardiopulmonary bypass (CPB), pulmonary ischemia/reperfusion (I/R) injury can cause acute lung injury (ALI). Our previous research confirmed that abnormal high-mobility group box 1 (HMGB1) release after CPB was closely related to ALI. However, the mechanism underlying the HMGB1-mediated induction of ALI after CPB is unclear. Our previous study found that HMGB1 binds Toll-like receptor 4 (TLR4), leading to lung injury, but direct evidence of a role for these proteins in the mechanism of CPB-induced lung injury has not been shown. We examined the effects of inhibiting HMGB1 or reducing TLR4 expression on CPB-induced lung injury in rats administered anti-HMBG1 antibody or TLR4 short-hairpin RNA (shTLR4), respectively. In these rat lungs, we studied the histologic changes and levels of interleukin- (IL-) 1β, tumour necrosis factor- (TNF-) α, HMGB1, and TLR4 after CPB. After CPB, the lung tissues from untreated rats showed histologic features of injury and significantly elevated levels of IL-1β, TNF-α, HMGB1, and TLR4. Treatment with anti-HMGB1 attenuated the CPB-induced morphological inflammatory response and protein levels of IL-1β, TNF-α, HMGB1, and TLR4 in the lung tissues and eventually alleviated the ALI after CPB. Treatment with shTLR4 attenuated the CPB-induced morphological inflammatory response and protein levels of IL-1β, TNF-α, and TLR4 in the lung tissues and eventually alleviated the ALI after CPB, but could not alleviate the HMGB1 protein levels induced by CPB. In summary, the present study demonstrated that the HMGB1/TLR4 pathway mediated the development of ALI induced by CPB.

Establishing an accurate and efficient source term estimation (STE) system is of great significance for identifying unknown gas leakage sources in urban environments. Many successful STE methods have been proposed, while most of them assume there is only one point source. However, the complicated urban atmospheric dispersion and the massive sensor data in distributed edge devices pose new challenges. To address these issues, this paper proposes a method to convert measured concentrations into visual features, which retains the characteristics of diffusion and the layout of obstacles. Then, a federated STE (FL-STE) framework is proposed to extract knowledge from local models collaboratively without collecting all privacy data, in which a deep neural network is used to recognize the relationship between visual features and source terms. Furthermore, we construct an urban dispersion dataset with multiple obstacles and sources by FDS simulation. Various empirical studies prove the efficiency of the proposed method.

Managed Aquifer Recharge (MAR) system is often adapted to alleviate drawdown cone and increase the water supply. In this study, an Open channel-Underground perforated pipe-Shaft system which included three identical subsystems was designed on the basis of local ditches, and applied at the Yellow River flood plain, Linqing city in North China. Three anti-clogging methods of the filter tank, inclined underground perforated pipe and shaft were adopted to lower the amount of fine suspended particles in source water. The dimensions and materials of each subsystem were tested and then determined by analytical method, numerical method and laboratory physical model experiment. The filter tank bottom area is 4 m2, perforated pipe diameter of 30 cm, length of 200 m made from plastic blind drains wrapped with geo-textile and 20 cm of coarse sand filled around, slope of 1/500, and the shaft depth of 10 m. A pilot project was constructed in the study area covering 5.4 hm2. Field recharge experiment and tracer test were conducted so as to monitor groundwater level and flow rate in perforated pipe. The measurements showed that the total infiltration amount attained from the field recharge experiment was 65,925 m3, which was close to the simulation results by analytical and numerical methods; the average velocity in the perforated pipe between the inlet and the shaft was 150 m/h approximately by both tracer test and theoretical calculation. This MAR project has the advantages of no energy consumption, no land occupation, managed groundwater recharge and water logging control. Therefore, its wider application in the location with similar conditions can be expected in future.

Jinan, Shandong Province, China frequently faces challenges related to spring protection and water supply security, and managed aquifer recharge (MAR) presents an effective solution to these challenges. Three MAR projects with multiple sources in Yufuhe River in Western Jinan City are conductive to increasing groundwater supply and maintaining groundwater levels. In order to determine the reasonable recharge flows and time, the hydrogeological conditions of the study area were described, the river infiltration recharge processes were simulated by Hydrus-2D software, and the recharge schemes for different groundwater depths were put forward. The results show that the model can achieve the better fitting effect. When the releasing flow is small, the optimal scheme is to continuously discharge water by 286800, 282500 and 282000 m3/d for 19.5, 12.7 and 10.5 days when the groundwater depth is 42, 30, 23 m at Cuima Village respectively. This study has certain significance for the efficient water lease of the Yufuhe River recharge project in Jinan City.

Investigating the hydraulic connectivity of a complex karst aquifer system is an important research topic for sustainable operation and optimization layout of karst groundwater exploitation and recharge. However, the identification of preferential sites of recharge and exploitation is usually subject to regional hydrogeology conditions and the mechanisms of recharge and exploitation. The conventional research methods of hydraulic connectivity often have some limitations. In this study, we developed an improved grey amplitude relation model to explore the hydraulic connectivity in Jinan spring catchment and presented a quantized evaluation index water table fluctuation relation degree (WTFRD) using karst groundwater table data in Western Jinan and Jinan spring groups from 2014 to 2017. Results showed that the total WTFRD was 0.854 between Western Jinan and Jinan spring groups when the external distraction for karst groundwater table was the smallest, which was in high relation degree grade. Meanwhile, the change rules of karst groundwater table in the two sites were basically the same. Accordingly, a high connectivity occurred between the two karst aquifers from a statistical perspective, and further illustrated that Western Jinan could be selected as preferential experiment sites. A comprehensive case in Jinan spring catchment indicated that the WTFRD provided a preliminary idea to investigate hydraulic connectivity quantitatively. This method could be considered as a pre-study of the conventional experiments to form a high-efficiency and low-cost combined method, which has great potential and merits further study.

Pulmonary fibrosis is a major cause of death in patients with acute respiratory distress syndrome (ARDS). Our previous study revealed that lipopolysaccharide (LPS) challenge could lead to mouse lung fibroblast proliferation. Additionally, inhibition of autophagy in lung fibroblasts was also reported to be crucial during the process of pulmonary fibrosis. However, the correlation between proliferation and inhibition of autophagy of lung fibroblasts and the underlying mechanism remain unknown. In this study, we report that autophagy was inhibited in mouse lung fibroblasts after LPS challenge, and was accompanied by activation of the PI3K-Akt-mTOR signaling pathway. Treating mouse lung fibroblasts with LPS resulted in mTOR and Akt phosphorylation, p62 up-regulation, and significant down-regulation of autophagosomes, which could be reversed by PI3K-Akt inhibitors (Ly294002) or mTOR inhibitors (rapamycin, RAPA). Furthermore, either LPS or hydroxychloroquine (HCQ), an autophagy inhibitor, could promote mouse lung fibroblast proliferation, which could be reversed by RAPA application. The present research therefore reveals that LPS promotes lung fibroblast proliferation through autophagy inhibition via activation of the PI3K-Akt-mTOR pathway.

Lipopolysaccharide (LPS)-induced proliferation of lung fibroblasts is closely correlated with loss of gene expression of thymocyte differentiation antigen-1 (Thy-1), accompanied with deacetylation of histones H3 and H4 at the Thy-1 gene promoter region; however, the mechanism remains enigmatic. We report here that LPS downregulates Thy-1 gene expression by activating histone deacetylases (HDACs) via Toll-like receptor 4 (TLR4) signaling. Treatment of primary cultured mouse lung fibroblasts with LPS resulted in significant upregulation of TLR4 and enhanced cell proliferation that was abolished by silencing TLR4 with lentivirus-delivered TLR4 shRNA. Interestingly, LPS increased the mRNA and protein levels of HDAC-4, -5, and -7, an effect that was abrogated by HDAC inhibitor trichostatin A (TSA) or TLR4-shRNA-lentivirus. Consistent with these findings, Ace-H3 and Ace-H4 were decreased by LPS that was prevented by TSA. Most importantly, chromosome immunoprecipitation (ChIP) analysis demonstrated that LPS decreased the association of Ace-H4 at the Thy-1 promoter region that was efficiently restored by pretreatment with TSA. Accordingly, LPS decreased the mRNA and protein levels of Thy-1 that was inhibited by TSA. Furthermore, silencing the Thy-1 gene by lentivirus-delivered Thy-1 shRNA could promote lung fibroblast proliferation, even in the absence of LPS. Conversely, overexpressing Thy-1 gene could inhibit lung fibroblast proliferation and reduce LPS-induced lung fibroblast proliferation. Our data suggest that LPS upregulates and activates HDACs through TLR4, resulting in deacetylation of histones H3 and H4 at the Thy-1 gene promoter that may contribute to Thy-1 gene silencing and lung fibroblast proliferation.

To evaluate the inhibitory effect of butyric acid (BA) as a histone deacetylase (HDAC) inhibitor on lipopolysaccharide (LPS)-induced pulmonary fibrosis and its mechanism.Thirty C57/BL6 mice were randomly divided into three groups according to the random number method, namely control group (physiological saline was given intraperitoneally and by gavage), LPS challenge group (LPS-induced murine model of pulmonary fibrosis was reproduced with intraperitoneal injection of 10 mg/kg LPS), and BA preconditioning + LPS challenge group (10 mg/kg BA was given followed by intraperitoneal injection of 10 mg/kg LPS), with 10 mice in each group. Mice were sacrificed painlessly, and lung tissue samples were harvested at 2 weeks and 4 weeks respectively (five samples every group each time). HDAC activity was evaluated with fluorescence analysis kit. Protein expression of acetylated-histone H3 (Ace-H3), acetylated-histone H4 (Ace-H4) and thymocyte differentiation antigen 1 (Thy-1) were determined by Western Blot. The mRNA expression of Thy-1 was assessed by real-time reverse transcription- polymerase chain reaction (real-time RT-PCR). The degree of lung inflammation and fibrosis were microscopic detected after hematoxylin-eosin (HE) staining and Masson collagen staining. The deposition of lung collagen was detected by hydroxyproline content measurement kit.Compared to control group, the degree of lung inflammation and fibrosis was aggravated after LPS challenge, as manifested by increased hydroxyproline content (μg/mg, 2 weeks: 8.384±0.632 vs. 4.388±0.334, 4 weeks: 8.308±0.244 vs. 4.370±0.342, both P0.01), increased HDAC activity (μmol/L, 2 weeks: 7.243±0.384 vs. 3.628±0.641, 4 weeks: 6.479±0.202 vs. 3.238±0.524, both P0.01), increased deacetylation degree of histone H3 and H4 [relative expression of Ace-H3 (gray value): 0.516±0.115 vs. 1.005±0.359 at 2 weeks, 0.633±0.143 vs. 1.092±0.193 at 4 weeks, both P0.05; relative expression of Ace-H4 (gray value): 0.402±0.164 vs. 0.759±0.187 at 2 weeks, P0.05; 0.426±0.098 vs. 0.858±0.177 at 4 weeks, P0.01], and lowered Thy-1 mRNA and protein expression [Thy-1 mRNA (2(-ΔΔCt)): 0.606±0.066 vs. 1.005±0.109 at 2 weeks, P0.01; 0.824±0.101 vs. 1.210±0.400 at 4 weeks, P0.05; relative expression of Thy-1 protein (gray value): 0.725±0.284 vs. 1.249±0.297 at 2 weeks, 0.589±0.139 vs. 1.372±0.343 at 4 weeks, both P0.05]. Compared with LPS group, BA precondition could inhibit above processes, as manifested by decreased hydroxyproline content (μg/mg: 5.943±0.726 vs. 8.384±0.632 at 2 weeks, 4.938±0.209 vs. 8.308±0.244 at 4 weeks, both P0.01), decreased HDAC activity (μmol/L: 4.386±0.117 vs. 7.243±0.384 at 2 weeks, 4.863±0.096 vs. 6.479±0.202 at 4 weeks, both P0.01), increased Thy-1 mRNA expression at 2 weeks (2(-ΔΔCt): 0.884±0.216 vs. 0.606±0.066, P0.05), increased acetylation degree of histone H4 and Thy-1 protein expression at 4 weeks [relative expression of Ace-H4 (gray value): 0.715±0.145 vs. 0.426±0.098, P0.05; relative protein expression of Thy-1 (gray value): 0.939±0.098 vs. 0.589±0.139, P0.01].LPS-induced pulmonary fibrosis was related with activation of HDAC, deacetylation of histone H3 and H4 and Thy-1 gene silencing. HDAC inhibitor BA could inhibit LPS-induced pulmonary fibrosis and Thy-1 gene silencing through inhibiting activation of HDAC and deacetylation of histone H4.

The mechanism underlying lipopolysaccharide (LPS)-induced aberrant proliferation of lung fibroblasts in Gram-negative bacilli-associated pulmonary fibrosis is unknown. High-mobility group box 1 (HMGB1) is a ubiquitous nuclear protein that is released from the nuclei of lung fibroblasts after LPS stimulation. It can exasperate LPS-induced inflammation and hasten cell proliferation. Thus, this study investigated the effects of LPS- and/or HMGB1-stimulating murine lung fibroblasts on gene expression using various assays in vitro. Thiazolyl-diphenyl-tetrazolium bromide (MTT) assay data showed that either LPS or HMGB1 could induce lung fibroblast proliferation. Endogenous HMGB1 secreted from lung fibroblasts was detected by enzyme-linked immunosorbent assay (ELISA) 48 h after LPS stimulation. Pretreatment with an anti-HMGB1 antibody inhibited the proliferative effects of LPS on lung fibroblasts. DNA microarray data showed that the NF-κB signaling genes were upregulated in cells after stimulated with LPS, HMGB1, or both. Secretion of matrix metalloproteinase (MMP)-2 and MMP-9, and tissue inhibitor of metalloproteinase 2 (TIMP-2) was significantly upregulated after treatment with LPS, HMGB1, or their combination. However, an NF-κB inhibitor was able to downregulate levels of these proteins. In addition, levels of Toll-like receptor 4 (TLR4), Toll-like receptor 2 (TLR2), and receptors for advanced glycation end products (RAGE) mRNA and proteins were also upregulated in these cells after LPS treatment and further upregulated by LPS plus HMGB1. In conclusion, the data from the current study demonstrate that LPS-induced lung fibroblast secretion of endogenous HMGB1 can augment the proproliferative effects of LPS and, therefore, may play a key role in exacerbation of pulmonary fibrosis. The underlying molecular mechanisms are related to the activation of the TLR4/NF-κB signaling pathway and its downstream targets.