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Introduction Previous studies revealed that gallic acid (GA) exerts anti‐inflammation and immuno‐regulatory properties. This study aims to explore the pharmacological activities of GA in collagen‐induced arthritis (CIA) mouse model. Methods Male DBA/1J mice were used to construct the CIA model. The mice were administrated with GA for 3 weeks. Clinical arthritis scores and hind paw volume were evaluated over the experimental period. qPCR and Western blot analysis were used to determine the levels of matrix metallopeptidases (MMPs) and cytokines. In addition, flow cytometry was used to measure the populations of Th17 and Treg cells. ELISAs were used to determine the cytokines in the serum and ankle joint tissues. Results Treatment of GA (40 and 80 mg/kg/d) reduced clinical arthritis scores and hind paw volume in the CIA mouse model. Besides, treatment of GA reduced the overexpression of MMPs and modulated the dysregulation of inflammation‐related cytokines. Flow cytometry showed that treatment of GA decreased the population of Th17 cells, and increased the population of Treg cells, as supported by treatment of GA regulated the Th17/Treg‐related cytokines. Conclusions GA attenuates symptoms in the CIA mouse model by anti‐inflammation and regulating Th17/Treg cell imbalance. 1. Treatment of GA (40 and 80 mg/kg/d) reduced clinical arthritis scores and hind paw volume in the CIA mouse model. 2. GA attenuates symptoms in the CIA mouse model by anti‐inflammation and regulating Th17/Treg cell imbalance.

Lycium barbarum L. is a widely used functional food and medicinal herb in Asian countries. L. barbarium polysaccharides (LBP) are considered as one of the major medicinal components of L. barbarium fruit and exhibits a wide range of biological activities. Here, we investigated the immunomodulatory effects of LBP and its uptake behaviors at the cellular level. LBP was prepared by water extraction and ethanol precipitation, and divided into two fractions based on the molecular weight distribution by ultrafiltration (LBP > 10 kDa and LBP < 10 kDa). The physicochemical properties of LBP and LBP fractions were well characterized. The LBP > 10 kDa fraction greatly enhanced the viability of macrophages RAW264.7 cells and induced cell polarization, but had weak effects to other tested tumor cell lines and normal cell line. This fraction could regulate the production of NO, TNF-α, IL-6 and ROS in RAW264.7 cells, suggesting both pro-inflammatory and anti-inflammatory effects. The dye-labeled LBP could be internalized into all tested cell lines and accumulated in lysosomes. The internalization of LBP in RAW264.7 cells is mainly through the clathrin-mediated endocytosis pathway. The Caco-2 intestinal transport experiment demonstrated that the dye labeled LBP could be transported through the Caco-2 cell monolayer (mimic intestinal epithelium) through clathrin-mediated endocytosis. These results demonstrate the immunomodulatory effects of LBP and its effective uptake by macrophages and intestine.

In this paper, a complete comparison analysis of two advanced control algorithms, namely robust model predictive control (MPC) and stochastic MPC, is performed in order to optimize the operation of a wind power generation system (WPGS). The power maximization often conflicts with the mechanical load experienced by the turbine in the full-load region (i.e., the higher the power extracted, the higher the load) under the wind speed disturbance, thereby leading to high maintenance cost resulting from the fatigue damage. Thus, a typical 5 MW wind turbine operating in a high-speed region is considered to guarantee system security and economy. The robust MPC is designed by utilizing the min–max framework to track steady-state optimum operating reference trajectory with the deterministic constraint of output power, while the stochastic MPC is constructed by incorporating the invariant set theory to also ensure the system security subjecting to the probabilistic constraint of output power. The relation between the constraints and the implications on optimal performance are also studied. Comprehensive simulations on a mechanism model and FAST simulator are carried out to demonstrate the validation of the two control methods under various scenarios. It is discovered that when wind speed in the near future can be predicted and utilized in controller design, the stochastic MPC can effectively reduce the maintenance cost by suppressing the constraint violation rate compared to robust MPC with a similar energy utilization due to the incorporation of the stochastic characteristics of wind speed.

Senescence of vascular smooth muscle cells (VSMCs) contributes to aging-related cardiovascular diseases by promoting arterial remodelling and stiffness. Ferroptosis is a novel type of regulated cell death associated with lipid oxidation. Here, we show that pro-ferroptosis signaling drives VSMCs senescence to accelerate vascular NAD + loss, remodelling and aging. Pro-ferroptotic signaling is triggered in senescent VSMCs and arteries of aged mice. Furthermore, the activation of pro-ferroptotic signaling in VSMCs not only induces NAD + loss and senescence but also promotes the release of a pro-senescent secretome. Pharmacological or genetic inhibition of pro-ferroptosis signaling, ameliorates VSMCs senescence, reduces vascular stiffness and retards the progression of abdominal aortic aneurysm in mice. Mechanistically, we revealed that inhibition of pro-ferroptotic signaling facilitates the nuclear-cytoplasmic shuttling of proliferator-activated receptor-γ and, thereby impeding nuclear receptor coactivator 4-ferrtin complex-centric ferritinophagy. Finally, the activated pro-ferroptotic signaling correlates with arterial stiffness in a human proof-of-concept study. These findings have significant implications for future therapeutic strategies aiming to eliminate vascular ferroptosis in senescence- or aging-associated cardiovascular diseases. Ferroptosis is a novel form of regulated cell death associated with lipid oxidation. Here, the authors demonstrate that the proferroptosis signal is activated and drives vascular aging by inducing senescence in vascular smooth muscle cells.

Background Proliferative vitreoretinopathy (PVR) is a blind-causing disease initiated by the activation of retinal pigmented epithelium (RPE) primarily induced by TGF-β families. Migrasome is a recently discovered type of extracellular vesicle related to cell migration. Results Here, we used ex vivo, in vitro, and in vivo models, to investigate the characteristics and functions of migrasomes in RPE activation and PVR development. Results indicated that the migrasome marker tetraspanin-4 (TSPAN4) was abundantly expressed in human PVR-associated clinical samples. The ex vivo model PVR microenvironment is simulated by incubating brown Norway rat RPE eyecups with TGF-β1. Electron microscope images showed the formation of migrasome-like vesicles during the activation of RPE. Further studies indicated TGF-β1 increased the expression of TSPAN4 which results in migrasome production. Migrasomes can be internalized by RPE and increase the migration and proliferation ability of RPE. Moreover, TSPAN4-inhibited RPE cells are with reduced ability of initiating experimental PVR. Mechanically, TSPAN4 expression and migrasome production are induced through TGF-β1/Smad2/3 signaling pathway. Conclusion In conclusion, migrasomes can be produced by RPE under PVR microenvironment. Migrasomes play a pivotal role in RPE activation and PVR progression. Thus, targeting TSPAN4 or blocking migrasome formation might be a new therapeutic method against PVR.

Background Although a variety of antidiabetic drugs have significant protective action on the cardiovascular system, it is still unclear which antidiabetic drugs can improve ventricular remodeling and fundamentally delay the process of heart failure. The purpose of this network meta-analysis is to compare the efficacy of sodium glucose cotransporter type 2 (SGLT-2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) agonists, metformin (MET), sulfonylurea (SU) and thiazolidinediones (TZDs) in improving left ventricular (LV) remodeling in patients with type 2 diabetes (T2DM) and/or cardiovascular disease (CVD). Methods We searched articles published before October 18, 2019, regardless of language or data, in 4 electronic databases: PubMed, EMBASE, Cochrane Library and Web of Science. We included randomized controlled trials in this network meta-analysis, as well as a small number of cohort studies. The differences in the mean changes in left ventricular echocardiographic parameters between the treatment group and control group were evaluated. Results The difference in the mean change in LV ejection fraction (LVEF) between GLP-1 agonists and placebo in treatment effect was greater than zero (MD = 2.04% [0.64%, 3.43%]); similar results were observed for the difference in the mean change in LV end-diastolic diameter (LVEDD) between SGLT-2 inhibitors and placebo (MD = − 3.3 mm [5.31, − 5.29]), the difference in the mean change in LV end-systolic volume (LVESV) between GLP-1 agonists and placebo (MD = − 4.39 ml [− 8.09, − 0.7]); the difference in the mean change in E/e′ between GLP-1 agonists and placebo (MD = − 1.05[− 1.78, − 0.32]); and the difference in the mean change in E/e′ between SGLT-2 inhibitors and placebo (MD = − 1.91[− 3.39, − 0.43]). Conclusions GLP-1 agonists are more significantly associated with improved LVEF, LVESV and E/e′, SGLT-2 inhibitors are more significantly associated with improved LVEDD and E/e′, and DPP-4 inhibitors are more strongly associated with a negative impact on LV end-diastolic volume (LVEDV) than are placebos. SGLT-2 inhibitors are superior to other drugs in pairwise comparisons.

Background: Ageing and type 2 diabetes mellitus (T2DM) are important risk factors for the development of cognitive deterioration and dementia. The objective of this research was to investigate the effects of an exercise intervention on cognitive function in older T2DM patients. Methods: Eight literature databases (PubMed, EBSCO, Scopus, Embase, The Cochrane Library, Web of Science, Ovid, and ProQuest) were searched from inception to January 20, 2022. The researchers examined Randomized controlled trials (RCTs) that evaluated the impact of exercise on the cognitive performance of older T2DM patients. The Cochrane risk-of-bias tool (ROB 2) for RCTs was used to assess each study. The quality of evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) approach. The Mini-Mental State Examination (MMSE), Modified MMSE (3MSE), and Montreal Cognitive Assessment (MoCA) were used to evaluate the cognitive outcomes. We performed a subgroup analysis with stratification according to exercise intervention modality, duration, and cognitive impairment. Results: Five trials were eligible, with a total of 738 T2DM patients. The combined findings revealed that exercise improved global cognitive function significantly (standardized mean difference: 1.34, 95% confidence interval: 0.23 – 2.44, p 0.05). In the studies that were included, no relevant adverse events were reported. Conclusions: Exercise is beneficial in improving global cognitive function in older adults with T2DM. Studies with bigger sample sizes and higher quality are additionally expected to draw more definite conclusions.

Objective To compare the superior‐level facet joint violations (FJV) between robot‐assisted (RA) percutaneous pedicle screw placement and conventional open fluoroscopic‐guided (FG) pedicle screw placement in a prospective cohort study. Methods This was a prospective cohort study without randomization. One‐hundred patients scheduled to undergo RA (n = 50) or FG (n = 50) transforaminal lumbar interbody fusion were included from February 2016 to May 2018. The grade of FJV, the distance between pedicle screws and the corresponding proximal facet joint, and intra‐pedicle accuracy of the top screw were evaluated based on postoperative CT scan. Patient demographics, perioperative outcomes, and radiation exposure were recorded and compared. Perioperative outcomes include surgical time, intraoperative blood loss, postoperative length of stay, conversion, and revision surgeries. Results Of the 100 screws in the RA group, 4 violated the proximal facet joint, while 26 of 100 in the FG group had FJV (P = 0.000). In the RA group, 3 and 1 screws were classified as grade 1 and 2, respectively. Of the 26 FJV screws in the FG group, 17 screws were scored as grade 1, 6 screws were grade 2, and 3 screws were grade 3. Significantly more severe FJV were noted in the FG group than in the RA group (P = 0.000). There was a statistically significant difference between RA and FG for overall violation grade (0.05 vs 0.38, P = 0.000). The average distance of pedicle screws from facet joints in the RA group (4.16 ± 2.60 mm) was larger than that in the FG group (1.92 ± 1.55 mm; P = 0.000). For intra‐pedicle accuracy, the rate of perfect screw position was greater in the RA group than in the FG group (85% vs 71%; P = 0.017). No statistically significant difference was found between the clinically acceptable screws between groups (P = 0.279). The radiation dose was higher in the FG group (30.3 ± 11.3 vs 65.3 ± 28.3 μSv; P = 0.000). The operative time in the RA group was significantly longer (184.7 ± 54.3 vs 117.8 ± 36.9 min; P = 0.000). Conclusions Compared to the open FG technique, minimally invasive RA spine surgery was associated with fewer proximal facet joint violations, larger facet to screw distance, and higher intra‐pedicle accuracy.

General cancer-targeted ligands that can deliver drugs to cells have been given considerable attention. In this paper, a high-affinity DNA aptamer (HG1) generally binding to human tumor cells was evolved by cell-SELEX, and was further optimized to have 35 deoxynucleotides (HG1-9). Aptamer HG1-9 could be taken up by live cells, and its target protein on a cell was identified to be human transferrin receptor (TfR). As a man-made ligand of TfR, aptamer HG1-9 was demonstrated to bind at the same site of human TfR as transferrin with comparable binding affinity, and was proved to cross the epithelium barrier through transferrin receptor-mediated transcytosis. These results suggest that aptamer HG1-9 holds potential as a promising ligand to develop general cancer-targeted diagnostics and therapeutics.

This paper proposes a UAV path planning method based on a Multi-strategy Secretary Bird Optimization Algorithm (MSBOA) to address the challenges of navigating complex terrain. First, a pooling mechanism is introduced to enhance population diversity and improve the algorithm’s optimization capabilities, balancing global exploration and local exploitation. Second, a dynamic fitness distance balance technique is incorporated to balance exploration and exploitation, preventing the population from becoming trapped in local optima while improving convergence accuracy. Finally, a greedy selection-based centroid reverse learning approach is used to update the population, enhancing the algorithm’s exploratory performance. To validate the effectiveness of the proposed improved algorithm, the proposed MSBOA is compared with classical and advanced intelligent algorithms by solving the CEC2017 benchmark test functions and a designed UAV environment model. Comparative analysis of simulation results indicates that the proposed MSBOA converges faster and achieves higher accuracy than the traditional SBOA. It effectively handles complex UAV path planning problems, enabling the design of faster, shorter and safer flight paths. This further demonstrates the excellent performance of the multi-strategy SBOA in UAV path planning, highlighting its broad application prospects.