Ventilation control of road tunnels towards disturbance suppression

Abstract In recent years, research on ventilating tunnels has become increasingly important. However, the impact of external disturbances on ventilating systems has been largely ignored. To address this issue of frequent airflow fluctuations caused by external perturbations, which cannot be fully compensated using conventional control methods, this study proposes a perturbation-compensated ventilation control approach. A disturbance compensator is developed by incorporating the tunnel’s airflow velocity and the number of jet fan start-stop events as input parameters. By compensating for external disturbances, the disturbance to the system is reduced. The Simulink model of the tunnel controller was used for simulation experiments. The compensator demonstrated good tracking results in comparison experiments with different disturbances. The ventilation approach based on disturbance compensator is capable of regulating the fluctuation of CO concentration within a justifiable range compared to using PID control and ADRC. This not only improves the stability of the entire control system but also significantly prolongs the service life of the jet fan by reducing the frequency of start-stop cycles

Objective diagnosis of machine learning method applicability to land comprehensive carrying capacity evaluation: A case study based on integrated RF and DPSIR models

The evaluation of land comprehensive carrying capacity (LCCC) is a popular topic in regional sustainable development and land science research. However, these evaluations are often not objective due to the complexity and nonlinear characteristics of the LCCC evaluation indicators. This study provides a new framework for using machine learning methods to objectively evaluate LCCC. The Driver-Pressure-State-Impact-Response (DPSIR) indicator conceptual framework was used for the spatial visualisation of indicators and was then combined with the random forest (RF) model to optimise the LCCC evaluation. The results showed the following: (1) The accuracy of the integrated RF and DPSIR model was better than that of traditional support vector machine (SVM) and principal component analysis (PCA) methods, indicating that RF model was more suitable for LCCC evaluations. (2) The contribution of the DPSIR indicators after RF optimisation was significantly different from that of the traditional analytic hierarchy process (AHP), the contribution of the influence subsystem (I) (48.7%) was enhanced, while the contribution of the drive subsystem (D) (6.8%) was weakened, demonstrating that after RF optimisation, the DPSIR was more conducive for handling complex nonlinear systems and objectively reflecting indicator contributions. (3) The objective attributes of the DPSIR indicators were optimised through the processing of spatial visualisation models, indicating that RF was suitable for processing evaluations with a multidimensional spatial heterogeneity index system. The LCCC evaluation model can be applied to other carrying capacity case studies and operational processes and provide a scientific method for handling the multidimensional nonlinear evaluation index system and objective evaluation of LCCC

Hypercysteinemia promotes atherosclerosis by reducing protein S-nitrosylation.

Protein S-nitrosylation plays important role in the regulation of cardiovascular functions in nitric oxide (NO) Pathway. Hypercysteinemia (HHcy) is an independently risk factor for atherosclerosis. We hypothesized that HHcy promotes atherosclerosis by reducing level of vascular protein S-nitrosylation. The aim of present study is to investigate effect of HHcy on vascular protein S-nitrosylation. A total of 45 male apoE-/- mice were randomly divided into three groups. The control group was fed a Western-type diet. The HHcy group was fed a diet containing 4.4% l-methionine, and the HHcy+NONOate group was fed a diet containing 4.4% l-methionine and administrated NONOate (ip). Human umbilical vein endothelial cells were performed for in vitro experiment. Plasma lipids were measured every 4 weeks. After 12 weeks, aortic atherosclerotic lesion areas were detected as well as cellular components. The levels of plasma homocysteine (Hcy) and NO were measured. S-nitrosylation was detected using immunofluorescence, and further confirmed by biotin switch method. We found that compared with the control group, Hcy levels, and atherosclerotic plaque, and content of vascular smooth muscle cells and macrophages in lesions significantly increased, and levels of NO significantly decreased in the HHcy group. However, NONOate reverses this effect. In addition, Hcy significantly reduced protein S-nitrosylation in human umbilical vein endothelial cells. This reduction of protein S-nitrosylation was accompanied by reduced levels of NO. Our results suggested that Hcy promoted atherosclerosis by inhibiting vascular protein S-nitrosylation

Epigallocatechin gallate attenuated high glucose-induced pancreatic beta cell dysfunction by modulating DRP1-mediated mitochondrial apoptosis pathways

Abstract Long-term exposure to hyperglycemic conditions leads to β-cell dysfunction, particularly mitochondrial dysfunction, and inflammatory and oxidative stress responses, which are considered the primary causes of β-cell death and the hallmarks of diabetes. Plant-active ingredients may play a key role in glycemic control. Epigallocatechin gallate (EGCG) is a characteristic catechin derived from tea that possesses anti-diabetic properties. Nonetheless, its underlying mechanisms remain elusive. Herein, the protective role of EGCG on high glucose (33 mM)-induced pancreatic beta cell dysfunction and its possible molecular mechanisms were investigated. Briefly, MIN6 cells were treated with glucose and EGCG (10 µM, 20 µM, and 40 µM) for 48 h. Our results revealed that EGCG dose-dependently restored mitochondrial membrane potential and concomitantly alleviated cell apoptosis. Mechanistically, the expression level of apoptotic protein BAX and Dynamic related protein 1 (DRP1) was significantly downregulated following EGCG treatment, whereas that of the anti-apoptotic protein BCL-2 was significantly upregulated. Taken together, EGCG alleviated high glucose-induced pancreatic beta cell dysfunction by targeting the DRP1-related mitochondrial apoptosis pathway and thus can serve as a nutritional intervention for the preservation of beta cell dysfunction in patients with type 2 diabetes mellitus

Targeted knockdown of PGAM5 in synovial macrophages efficiently alleviates osteoarthritis

Abstract Osteoarthritis (OA) is a common degenerative disease worldwide and new therapeutics that target inflammation and the crosstalk between immunocytes and chondrocytes are being developed to prevent and treat OA. These attempts involve repolarizing pro-inflammatory M1 macrophages into the anti-inflammatory M2 phenotype in synovium. In this study, we found that phosphoglycerate mutase 5 (PGAM5) significantly increased in macrophages in OA synovium compared to controls based on histology of human samples and single-cell RNA sequencing results of mice models. To address the role of PGAM5 in macrophages in OA, we found conditional knockout of PGAM5 in macrophages greatly alleviated OA symptoms and promoted anabolic metabolism of chondrocytes in vitro and in vivo. Mechanistically, we found that PGAM5 enhanced M1 polarization via AKT-mTOR/p38/ERK pathways, whereas inhibited M2 polarization via STAT6-PPARγ pathway in murine bone marrow-derived macrophages. Furthermore, we found that PGAM5 directly dephosphorylated Dishevelled Segment Polarity Protein 2 (DVL2) which resulted in the inhibition of β-catenin and repolarization of M2 macrophages into M1 macrophages. Conditional knockout of both PGAM5 and β-catenin in macrophages significantly exacerbated osteoarthritis compared to PGAM5-deficient mice. Motivated by these findings, we successfully designed mannose modified fluoropolymers combined with siPGAM5 to inhibit PGAM5 specifically in synovial macrophages via intra-articular injection, which possessed desired targeting abilities of synovial macrophages and greatly attenuated murine osteoarthritis. Collectively, these findings defined a key role for PGAM5 in orchestrating macrophage polarization and provides insights into novel macrophage-targeted strategy for treating OA

Mediator 1 Is Atherosclerosis Protective by Regulating Macrophage Polarization

ObjectiveMED1 (mediator 1) interacts with transcription factors to regulate transcriptional machinery. The role of MED1 in macrophage biology and the relevant disease state remains to be investigated.Approach and resultsTo study the molecular mechanism by which MED1 regulates the M1/M2 phenotype switch of macrophage and the effect on atherosclerosis, we generated MED1/apolipoprotein E (ApoE) double-deficient (MED1ΔMac/ApoE-/-) mice and found that atherosclerosis was greater in MED1ΔMac/ApoE-/- mice than in MED1fl/fl/ApoE-/- littermates. The gene expression of M1 markers was increased and that of M2 markers decreased in both aortic wall and peritoneal macrophages from MED1ΔMac/ApoE-/- mice, whereas MED1 overexpression rectified the changes in M1/M2 expression. Moreover, LDLR (low-density lipoprotein receptor)-deficient mice received bone marrow from MED1ΔMac mice showed greater atherosclerosis. Mechanistically, MED1 ablation decreased the binding of PPARγ (peroxisome proliferator-activated receptor γ) and enrichment of H3K4me1 and H3K27ac to upstream region of M2 marker genes. Furthermore, interleukin 4 induction of PPARγ and MED1 increased the binding of PPARγ or MED1 to the PPAR response elements of M2 marker genes.ConclusionsOur data suggest that MED1 is required for the PPARγ-mediated M2 phenotype switch, with M2 marker genes induced but M1 marker genes suppressed. MED1 in macrophages has an antiatherosclerotic role via PPARγ-regulated transactivation

Development of Cell-Active <i>N</i>⁶‑Methyladenosine RNA Demethylase FTO Inhibitor

The direct nucleic acid repair dioxygenase FTO is an enzyme that demethylates <i>N</i>⁶-methyladenosine (m⁶A) residues in mRNA <i>in vitro</i> and inside cells. FTO is the first RNA demethylase discovered that also serves a major regulatory function in mammals. Together with structure-based virtual screening and biochemical analyses, we report the first identification of several small-molecule inhibitors of human FTO demethylase. The most potent compound, the natural product rhein, which is neither a structural mimic of 2-oxoglutarate nor a chelator of metal ion, competitively binds to the FTO active site <i>in vitro</i>. Rhein also exhibits good inhibitory activity on m⁶A demethylation inside cells. These studies shed light on the development of powerful probes and new therapies for use in RNA biology and drug discovery