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Wound healing impairment is a frequent diabetes problem leading to amputation. Hyperglycemia induces the overproduction of reactive oxygen species (ROS), iron overload and sustained inflammation, resulting in the persistence of chronic wounds. However, the intrinsic mechanisms of impaired diabetic wound healing remain enigmatic. A new non-apoptotic regulatory cellular death called Ferroptosis, is distinguished by iron-driven lipid peroxidation products accumulation along with insufficient antioxidant enzymes. A decline in antioxidant capacity, excess accumulation of peroxidation of iron and lipid have been identified in wound sites of streptozotocin-induced diabetes mellitus (DM) rats and elevated glucose (EG)-cultured macrophages. Additionally, sustained inflammation and increased inflammatory cytokines were observed in DM rats and HG-cultured macrophages. Importantly, ferrostatin-1 (Fer-1) is a ferroptosis suppressor treatment significantly ameliorated diabetes-related ferroptosis and inflammation. This treatment also enhanced cell proliferation and neovascularization, ultimately thereby accelerating diabetic wound healing. Meanwhile, our study demonstrated that an anti-ferroptotic and anti-inflammatory effects of Fer-1 were mediated through stimulation of nuclear erythroid-associated factor 2 (Nrf2). The current study may provide a new rationale for diabetic wound healing.

Open-pit coal mining inevitably damages the soil and vegetation in mining areas. Currently, the restoration of cold and arid open-pit mines in Xinjiang, China, is still in the initial exploratory stage, especially the changes in soil nutrients in spoil dumps over time. Dynamic remote sensing monitoring of vegetation in mining areas and their correlation are relatively rare. Using the Heishan Open Pit in Xinjiang, China, as a case, soil samples were collected during different discharge periods to analyze the changes in soil nutrients and uncover the restoration mechanisms. Based on four Landsat images from 2018 to 2023, the remote sensing ecological index (RSEI) and fractional vegetation cover (FVC) were obtained to evaluate the effect of mine restoration. Additionally, the correlation between vegetation changes and soil nutrients was analyzed. The results indicated that (i) the contents of nitrogen (N), phosphorus (P), potassium (K), and organic matter (OM) in the soil increased with the duration of the restoration period. (ii) When the restoration time of the dump exceeds 5 years, N, P, K, and OM content is higher than that of the original surface-covered vegetation area. (iii) Notably, under the same restoration aging, the soil in the artificial mine restoration demonstration base had significantly higher contents of these nutrients compared to the soil naturally restored in the dump. (iv) Over the past five years, the RSEI and FVC in the Heishan Open Pit showed an overall upward trend. The slope remediation and mine restoration project significantly increased the RSEI and FVC values in the mining area. (v) Air humidity and surface temperature were identified as key natural factors affecting the RSEI and FVC in cold and arid open pit. The correlation coefficients between soil nutrient content and vegetation coverage were higher than 0.78, indicating a close and complementary relationship between the two. The above results can clarify the time–effect relationship between natural recovery and artificial restoration of spoil dumps in cold and arid mining areas in Xinjiang, further promoting the research and practice of mine restoration technology in cold and arid open pits.

Abstract Hyperglycemia is an independent risk factor for the rapid progression of nonalcoholic steatohepatitis (NASH) to liver fibrosis with an incompletely defined mechanism. Ferroptosis is a novel form of programmed cell death that has been identified as a pathogenic mechanism in various diseases. However, the role of ferroptosis in the development of liver fibrosis in NASH with type 2 diabetes mellitus (T2DM) is unclear. Here, we observed the histopathological features of the progression of NASH to liver fibrosis as well as hepatocyte epithelial-mesenchymal transition (EMT) in a mouse model of NASH with T2DM and high-glucose-cultured steatotic human normal liver (LO2) cells. The distinctive features of ferroptosis, including iron overload, decreased antioxidant capacity, the accumulation of reactive oxygen species, and elevated lipid peroxidation products, were confirmed in vivo and in vitro. Liver fibrosis and hepatocyte EMT were markedly alleviated after treatment with the ferroptosis inhibitor ferrostatin-1. Furthermore, a decrease in the gene and protein levels of AGE receptor 1 (AGER1) was detected in the transition from NASH to liver fibrosis. Overexpression of AGER1 dramatically reversed hepatocyte EMT in high-glucose-cultured steatotic LO2 cells, whereas the knockdown of AGER1 had the opposite effect. The mechanisms underlying the phenotype appear to be associated with the inhibitory effects of AGER1 on ferroptosis, which is dependent on the regulation of sirtuin 4. Finally, in vivo adeno-associated virus-mediated AGER1 overexpression effectively relieved liver fibrosis in a murine model. Collectively, these findings suggest that ferroptosis participates in the pathogenesis of liver fibrosis in NASH with T2DM by promoting hepatocyte EMT. AGER1 could reverse hepatocyte EMT to ameliorate liver fibrosis by inhibiting ferroptosis. The results also suggest that AGER1 may be a potential therapeutic target for the treatment of liver fibrosis in patients with NASH with T2DM. Chronic hyperglycemia is associated with increased advanced glycation end products, resulting in the downregulation of AGER1. AGER1 deficiency downregulates Sirt4, which disturbs key regulators of ferroptosis (TFR-1, FTH, GPX4, and SLC7A11). These lead to increased iron uptake, decreasing the antioxidative capacity and enhanced lipid ROS production, ultimately leading to ferroptosis, which further promotes hepatocyte epithelial-mesenchymal transition and fibrosis progression in NASH with T2DM.

Obesity is a global epidemic which induces a multitude of metabolic disorders. Browning of white adipose tissue (WAT) has emerged as a promising therapeutic strategy for promoting weight loss and improving associated metabolic syndromes in people with obesity. However, current methods of inducing white adipose tissue browning have limited applicability. We developed a nanocomplex pTSL@(P+I), which is a temperature-sensitive liposome (TSL) surface-conjugated with an adipocyte-targeting peptide (p) and loaded with both browning-promoting agents (P) and photosensitizing agents (I). This nanocomplex exhibits adipocyte targeting, as well as synergistic pharmacological and photothermal properties to promote browning. pTSL@(P+I) effectively upregulates UCP1 and COX5B expression by activating the transcription axis of PPARγ/PGC1α and HSF1/PGC1α, thereby promoting white adipose tissue browning and reducing obesity. This novel nanocomplex exhibited a uniform spherical shape, with an average diameter of approximately 200 nm. Additionally, the nanocomplexes exhibited remarkable photothermal properties and biocompatibility. Further, when adipocytes were treated with pTSL@(P+I), their triglyceride content decreased remarkably and intracellular mitochondrial activity increased significantly. When applied to diet-induced obesity (DIO) mice, the nanocomplex exhibited significant efficacy, demonstrating a notable 14.4% reduction in body weight from the initial measurement, a decreased fat/lean mass ratio of 20.8%, and no statistically significant disparities (p > 0.05) in associated side effects when compared to the control group. In summary, implementation of the targeted nanocomplex pTSL@(P+I) to enhance energy expenditure by stimulating white adipose tissue browning offers a promising therapeutic approach for the treatment of obesity and related metabolic syndromes.

The existing trajectory planning research mainly considers the safety of the obstacle avoidance process rather than the anti-rollover requirements of heavy vehicles. When there are driving risks such as rollover and collision, how to coordinate the game relationship between the two is the key technical problem to realizing the anti-rollover trajectory planning under the condition of driving risk triggering. Given the above problems, this paper studies the non-cooperative game model construction method of the obstacle avoidance process that integrates the vehicle driving risk in a complex traffic environment. Then it obtains the obstacle avoidance area that satisfies both the collision and rollover profit requirements based on the Nash equilibrium. A Kmeans-SMOTE risk clustering fusion is proposed in this paper, in which more sampling points are supplemented by the SMOTE oversampling method, and then the ideal obstacle avoidance area is obtained through clustering algorithm fusion to determine the optimal feasible area for obstacle avoidance trajectory planning. On this basis, to solve the convergence problems of the existing multi-objective particle swarm optimization algorithm and analyze the influence of weight parameters and the diversity of the optimization process, this paper proposes an anti-rollover trajectory planning method based on the improved cosine variable weight factor MOPSO algorithm. The simulation results show that the trajectory obtained based on the method proposed in this paper can effectively improve the anti-rollover performance of the controlled vehicle while avoiding obstacles.

Since the implementation of changing coal into clean energy heating in the Beijing–Tianjin–Hebei region, there has been a tremendous change in terms of air quality during the winter in the north. On the basis of field research for resort sample room setting up in the Yanqing district , Beijing, this paper mainly expounds the cold and heat sources and system solutions used by resort villas to meet the needs of hot water, heating, and cooling throughout the year, and introduces a new type of solar energy ‘The heat pump direct floor radiant heating system’ (called “Trinity”), which can combine air source heat pump-solar system and direct floor radiant heating to ensure the efficient and stable operation of the heating system while making full use of solar energy. Moreover, with the combination of modeling analysis on the annual load via DeST software, the result of actual measurement sees “Trinity” system as the optimal solution not only by means of comparing the heating scheme of the original single air source heat pump unit and the solar energy + air source heat pump unit’s simulation comparison, it was concluded that the initial investment of scheme two was 16,969 yuan and the initial investment of scheme two was 17,352 yuan. The annual operating cost of the second option is 3577.8 yuan, and the annual operating cost of the second option is only about one-half of the annual operating cost of the second option. Based on the calculation of the investment recovery period, the cost savings of the second option after only 0.15 years is net income. Therefore, the “Trinity” scheme is selected as the best scheme.

Aims: The objectives of this study were to identify clinical predictors of the Traditional Chinese medicine (TCM) clinical index for diabetic peripheral neuropathy (DPN) in type 2 diabetes mellitus (T2DM) patients, develop a clinical prediction model, and construct a nomogram. Methods: We collected the TCM clinical index from 3590 T2DM recruited at the Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine from January 2019 to October 2020. The participants were randomly assigned to either the training group (n = 3297) or the validation group (n = 1426). TCM symptoms and tongue characteristics were used to assess the risk of developing DPN in T2DM patients. Through 5-fold cross-validation in the training group, the least absolute shrinkage and selection operator (LASSO) regression analysis method was used to optimize variable selection. In addition, using multifactor logistic regression analysis, a predictive model and nomogram were developed. Results: A total of eight independent predictors were found to be associated with the DPN in multivariate logistic regression analyses: advanced age of grading (odds ratio/OR 1.575), smoke (OR 2.815), insomnia (OR 0.557), sweating (OR 0.535), loose teeth (OR 1.713), dry skin (OR 1.831), purple tongue (OR 2.278). And dark red tongue (OR 0.139). The model was constructed using these eight predictor's medium discriminative capabilities. The area under the curve (AUC) of the training set is 0.727, and the AUC of the validation set is 0.744 on the ROC curve. The calibration plot revealed that the model's goodness-of-fit is satisfactory. Conclusions: We established a TCM prediction model for DPN in patients with T2DM based on the TCM clinical index.

The efficacious delivery of antimicrobial drugs to intractable oral biofilms remains a challenge due to inadequate biofilm penetration and lack of pathogen targeting. Herein, we have developed a microenvironment-activated poly(ethylene glycol) (PEG)-sheddable nanoplatform to mediate targeted delivery of drugs into oral biofilms for the efficient prevention of dental caries. The PEGylated nanoplatform with enhanced biofilm penetration is capable of deshielding the PEG layer under slightly acidic conditions in a PEG chain length-dependent manner to re-expose the bacteria-targeting ligands, thereby facilitating targeted codelivery of ciprofloxacin (CIP) and IR780 to the bacteria after accumulation within biofilms. The nanoplatform tends to induce bacterial agglomeration and suffers from degradation in the acidic oral biofilm microenvironment, triggering rapid drug release on demand around bacterial cells. The self-modulating nanoplatform under near-infrared (NIR) irradiation accordingly displays greatly augmented potency in oral biofilm penetration and disruption compared with drugs alone. Topical oral treatment with nanoplatforms involving synergetic pharmacological and photothermal/photodynamic trinary therapy results in robust biofilm dispersion and efficacious suppression of severe tooth decay in rats. This versatile nanoplatform can promote local accumulation and specific drug transport into biofilms and represents a new paradigm for targeted drug delivery for the management of oral biofilm-associated infections.

Abstract Numerous studies have shown that long noncoding RNAs (LncRNAs) are involved in the development and immune escape of head and neck squamous-cell carcinoma (HNSCC). However, the specific regulatory mechanisms by which LINC01123 regulates HNSCC and its correlation with immunity remain unclear. Therefore, this study’s primary purpose was to explore the mechanisms by which LINC01123 regulates the immune escape and progression of HNSCC. This study confirmed that LINC01123 is competitively bound to miR-214-3p, and miR-214-3p specifically targets B7–H3. The effects of LINC01123, B7–H3, and miR-214-3p on tumor progression, CD8+T-cell-mediated immune response, and the tumorigenicity of HNSCC in vitro and in vivo were examined through the downregulation or upregulation of LINC01123, B7–H3, and miR-214-3p. Our results indicated that LINC01123 and B7–H3 were highly expressed in HNSCC and are associated with poor prognosis in patients. Notably, overexpression of LINC01123 or B7–H3 or downregulation of miR-214-3p inhibited the function of CD8+T cells and promoted the progression of HNSCC. Therefore, LINC01123 acts as a miR-214-3p sponge to inhibit the activation of CD8+T cells and promote the progression of HNSCC by upregulating B7–H3.

BackgroundNanomaterials have recently been shown to have a considerable advantage in promoting wound healing in diabetic patients or animal models. However, no bibliometric analysis has been conducted to evaluate global scientific production. Herein, this study aimed to summarize the current characteristics, explore research trends, and clarify the direction of nanomaterials and diabetic wound healing in the future.MethodsRelevant publications from 2011 to 2021 were collected from the Web of Science Core Collection on October 3, 2022. VOSviewer, CiteSpace, bibliometrix-R package, Origin 2021, and Microsoft Excel 2019 were used for bibliometric and visualization analyses.ResultsWe identified 409 publications relating to nanomaterials and diabetic wound healing. The number of annual productions remarkably increased from 2011 to 2021, with China and Shanghai Jiao Tong University being the most productive. The most prolific authors were Hasan Anwarul. The leading journal was the International Journal of Biological Macromolecules, with 22 publications. The most popular keywords were “nanoparticles,” “delivery,” “in vitro,” “electrospinning,” “angiogenesis,” and “antibacterial.” Keyword burst analysis showed “cerium oxide,” “matrix metalloproteinase 9,” “composite nanofiber,” “hif 1 alpha,” and “oxide nanoparticle” were emerging research hotspots.ConclusionWe found there has been a great progress in the application of nanomaterials in diabetic wound healing from 2011 to 2021. Although many researchers and institutions from different countries or regions contributed contributed to publications, it will be helpful or the development of this field if the degree of international cooperation can be enhanced. In the future, nanomaterials with powerful antioxidant and antibacterial qualities and promoting angiogenesis are the research hotspots.

Abstract Background Time-restricted feeding is an emerging dietary intervention that is becoming increasingly popular. There are, however, no randomised clinical trials of time-restricted feeding in overweight patients with type 2 diabetes. Here, we explored the effects of time-restricted feeding on glycaemic regulation and weight changes in overweight patients with type 2 diabetes over 12 weeks. Methods Overweight adults with type 2 diabetes (n = 120) were randomised 1:1 to two diet groups: time-restricted feeding (n = 60) or control (n = 60). Sixty patients participated in a 10-h restricted feeding treatment program (ad libitum feeding from 8:00 to 18:00 h; fasting between 18:00 and 8:00 h) for 12 weeks. Results Haemoglobin A1c and body weight decreased in the time-restricted feeding group (− 1.54% ± 0.19 and − 2.98 ± 0.43 kg, respectively) relative to the control group over 12 weeks (p

Introduction: Obesity is associated with an increased risk of inflammatory bowel disease (IBD), whereas not all obese individuals have the same effect. In individuals with obesity, the role of metabolic status in the readmission of IBD remains unclear. Our study aimed to evaluate the association between different obesity metabolic phenotypes and the prognosis of IBD patients. Methods: We conducted a longitudinal cohort study using Nationwide Readmissions Database (NRD) (2018 sample). Out of 12,928,231 discharge records, 63,748 records with a discharge diagnosis of IBD were identified for analysis. Cox proportional hazard ratio (HR) with 95% confidence interval (CI) was calculated, adjusting for potential confounders. Results: During a 180-day follow-up in IBD patients with different obesity metabolic phenotypes, all-cause readmission rate, inpatient mortality rate, unplanned readmission rate, total charge, hospitalized length of stay were statistically different (all p < 0.001). After multivariate Cox regression analysis, IBD patients with metabolically unhealthy nonobese (MUNO) had higher risk of readmission (all-cause and unplanned) (HR 1.04, 95% CI: 1.00–1.08 and HR 1.06, 95% CI: 1.02–1.10), and those with metabolically unhealthy obesity (MUO) had higher risk of unplanned readmission (HR 1.08, 95% CI: 1.02–1.15). In subgroup analysis, both the MUNO group and MUO group had higher risk of readmission (all-cause and unplanned) in the ulcerative colitis (UC) subgroup, but only the MUNO group had higher risk of readmission (all-cause and unplanned) (HR 1.05, 95% CI: 1.00–1.10 and HR 1.06, 95% CI: 1.01–1.12) in the Crohn’s disease (CD) subgroup. Conclusion: Metabolic abnormalities were associated with an increased risk of readmission in patients with IBD, regardless of obesity.

Diabetic kidney disease (DKD) progression can be predicted by abnormalities in the tubulointerstitial lining, and their treatment may be useful for preventing the disease. DKD is a progressive disease that contributes to renal tubular cell death, but its underlying mechanisms remain unclear. Ferroptosis is a novel term linked to lipid hydroperoxidation, and it plays an important role in the pathogenesis of DKD. Overexpression of cyclooxygenase-2 (COX2), an enzyme of the proximal tubule, causes cellular redox damage in DKD. It remains unknown whether COX2 exacerbates tubular damage by accelerating ferroptosis in the kidneys of diabetic mice. HK-2 cells cultured in high glucose exhibited ferroptosis, which was inhibited by ferroptosis inhibitors. Additionally, alterations in the sensors of ferroptosis metabolism, such as glutathione peroxidase 4 (GPX4) activity, lipid hydroperoxidation, reduced glutathione (GSH) levels and changes in mitochondrial morphology, were observed in high glucose-cultured HK-2 cells. Diabetic mice manifested tubular injury and deranged renal physiological indices, which were mitigated by ferrostatin-1 (Fer-1). Importantly, these perturbations were ameliorated by downregulating COX2. In addition, the increased COX2 was observed to be elevated in the daibetic kindney. To explore the relevance of COX2 to ferroptosis, HK-2 cells that knocked down from COX2 exhibited decreased ferroptosis sensitivity under high glucose conditions. In RSL-3-treated HK-2 cells, ferroptosis was improved by downregulating COX2 by treatment with aspirin, which was confirmed in high glucose-cultured HK-2 cells. Furthermore, the ferroptosis changes were also suppressed by decreasing COX2 in diabetic mice treated with aspirin, which retarded DKD progression. In conclusion, our results demonstrated that ferroptosis in renal tubular cells contributes to DKD development and that diabetes-related ferroptosis was inhibited through the downregulation of COX2 by aspirin, thus retarding the progression of DKD. Our findings support a renoprotective mechanism by which aspirin inhibits COX2 activation, identify COX2 as a potential target of ferroptosis, and establish that ferroptosis in renal tubular cells is an integral process in the pathogenesis of DKD regulated by COX2 expression profiles.

Objective. Astragalus mongholicus Bunge [Fabaceae] (AMB), a traditional Chinese medicine (TCM), has been widely used to treat liver diseases in the clinic. However, the efficacy and mechanism of AMB in the treatment of nonalcoholic fatty liver disease (NAFLD) remain unclear. The purpose of this study was to systematically investigate the active components and mechanisms of AMB against NAFLD based on network pharmacology, molecular docking, and experimental verification. Methods. First, the bioactive components and relevant targets of AMB were screened from the Traditional Chinese Medicine Systematic Pharmacology (TCMSP) database, and NAFLD-related targets were obtained from the GeneCards database. Then, the AMB-NAFLD protein target interaction network was built by the STRING database. GO and KEGG pathway enrichment analyses were performed using the DAVID database. The component targets were visualized using Cytoscape software. Finally, molecular docking and experiments were used to verify the results of network pharmacological prediction. Results. Network pharmacology predicted that quercetin may be the main active component in AMB, and the TNF and MAPK signaling pathways may be the key targets of AMB against NAFLD. Molecular docking validation results demonstrated that quercetin, as the main active component of AMB, had the highest binding affinity with TNF. Furthermore, quercetin played a distinct role in alleviating NAFLD through in vitro experiments. Quercetin upregulated the phosphorylation levels of AMPK and inhibited the expression of p-MAPK and TNF-α. In addition, we further discovered that quercetin could increase ACC phosphorylation and CPT1α expression in PA-induced HepG2 cells. Conclusions. Our results indicated that quercetin, as the main active component in AMB, exerts an anti-NAFLD effect by regulating the AMPK/MAPK/TNF-α and AMPK/ACC/CPT1α signaling pathways to inhibit inflammation and alleviate lipid accumulation.

PurposeSleep duration is thought to play a key role in the development of metabolic syndrome. However, the results have been inconsistent.MethodsWe conducted a systematic review and meta-analysis of cohort studies and searched publications in PubMed, Embase, Cochrane Central Register of Controlled Trials, and Clinicaltrials.gov. The summary relative risks (RRs) were estimated using a random model. The sensitivity analysis was performed by sequentially excluding each study to test the robustness of the pooled estimates.FindingWe included 13 studies involving 300,202 patients in which short sleep and long sleep significantly increased the risk of metabolic syndrome 15% (RR = 1.15, 95%CI = 1.09-1.22, p < 0.001) and 19% (RR = 1.19, 95%CI = 1.05-1.35, p < 0.001). Moreover, the relationship between sleep duration and metabolic syndrome risk presented a U-shaped curve. Short and long sleep increased the risk of obesity by 14% (RR = 1.14, 95%CI = 1.07-1.22, p

Abstract In this paper, we propose an inexact version of proximal gradient algorithm with extrapolation for solving a class of nonconvex nonsmooth optimization problems. Specifically, the subproblem in proximal gradient algorithm with extrapolation is allowed to be solved inexactly by certain relative error criterion, in the sense that the criterion can be updated adaptively in each iteration. Under the assumption that an auxiliary function satisfies the Kurdyka–Łojasiewicz (KL) inequality, we prove that the iterative sequence generated by the inexact proximal gradient algorithm with extrapolation converges to a stationary point of the considered problem. Furthermore, the convergence rate of the proposed algorithm can be established when the KL exponent is known. Moreover, we illustrate the advantage by applying the algorithm to solve a nonconvex optimization problem.

In order to provide a more comprehensive depiction of the actual heat transfer process in energy piles, this research paper presents an approximate solution for a finite line heat source model operating under variable heat flow conditions. This solution is established by integrating the finite line heat source model and the superposition principle. Furthermore, the W-tube heat exchanger is divided into many segments, and a segmented superposition approach is used based on the thermal response. Consequently, a heat transfer model for a single-pile heat source is formulated, taking into consideration the heat exchange between the circulating water and the energy pile. Notably, the soil temperature predicted by this proposed model closely aligns with the results obtained from the FLUENT numerical model, thereby substantiating the accuracy of the proposed approach. Simultaneously, the heat transfer model is employed to analyze variations in temperature and heat flux density within the heat exchanger and to investigate the influence of parameters such as mass-flow rate, pile-soil heat transfer coefficient, pile-soil density, and pile-soil specific heat capacity on the heat transfer characteristics of energy piles. This model enables the determination of time-varying heat flux and precise outlet temperature, thereby facilitating a rapid assessment of the heat transfer efficiency of energy piles. [ABSTRACT FROM AUTHOR]

In order to study the effect of vibration direction on vibration-assisted fixed abrasive polishing and explore the influence rule of vibration direction on material removal rate and workpiece surface quality, a single abrasive particle vibration-assisted fixed abrasive polishing model was established to study the effect of axial and radial vibration on workpiece profile depth, surface morphology, etc. And the experiments of vibration-assisted fixed abrasive polishing in different vibration directions were carried out. The results show that axial vibration auxiliary polishing can greatly advance the processing efficiency, and improve the workpiece material removal rate by 27.6%; radial vibration auxiliary polishing can achieve better surface quality, and reduces the surface roughness by 59.8%. [ABSTRACT FROM AUTHOR]