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Pneumoconiosis is one of the most serious occupational diseases worldwide. Silicosis due to prolonged inhalation of free silica dust during occupational activities is one of the main types. Cuproptosis is a newly discovered mode of programmed cell death characterized by the accumulation of free copper in the cell, which ultimately leads to cell death. Increased copper in the serum of silicosis patients, suggests that the development of silicosis is accompanied by changes in copper metabolism, but whether cuproptosis is involved in the progression of silicosis is actually to be determined. To test this hypothesis, we screened the genetic changes in patients with idiopathic fibrosis by bioinformatics methods and predicted and functionally annotated the cuproptosis-related genes among them. Subsequently, we established a mouse silicosis model and detected the concentration of copper ions and the activity of ceruloplasmin (CP) in serum, as well as changes of the concentration of copper and cuproptosis related genes in mouse lung tissues. We identified 9 cuproptosis-related genes among the differential genes in patients with IPF at different times and the tissue-specific expression levels of ferredoxin 1 (FDX1) and Lipoyl synthase (LIAS) proteins. Furthermore, serum CP activity and copper ion levels in silicosis mice were elevated on days 7th and 56th after silica exposure. The expression of CP in mouse lung tissue elevated at all stages after silica exposure. The mRNA level of FDX1 decreased on days 7th and 56th, and the protein level remained in accordance with the mRNA level on day 56th. LIAS and Dihydrolipoamide dehydrogenase (DLD) levels were downregulated at all times after silica exposure. In addition, Heatshockprotein70 (HSP70) expression was increased on day 56. In brief, our results demonstrate that there may be cellular cuproptosis during the development of experimental silicosis in mice and show synchronization with enhanced copper loading in mice.

Manganese is essential trace elements, to participate in the body a variety of biochemical reactions, has important physiological functions, such as stimulate the immune cell proliferation, strengthen the cellular immunity, etc. However, excessive manganese exposure can cause damage to multiple systems of the body.The immune system is extremely vulnerable to external toxicants, however manganese research on the immune system are inadequate and biomarkers are lacking. Therefore, here we applied a manganese-exposed rat model to make preliminary observations on the immunotoxic effects of manganese. We found that manganese exposure inhibited humoral immune function in rats by decreasing peripheral blood IgG (ImmunoglobulinG, IgG), IgM (ImmunoglobulinM, IgM) and complement C3 levels; It also regulates rat cellular immune activity by influencing peripheral blood, spleen, and thymus T cell numbers and immune organ ICs (Immune Checkpoints, ICs) and cytokine expression. Furthermore, it was revealed that the impact of manganese exposure on the immune function of rats exhibited a correlation with both the dosage and duration of exposure. Notably, prolonged exposure to high doses of manganese had the most pronounced influence on rat immune function, primarily manifesting as immunosuppression.The above findings suggest that manganese exposure leads to impaired immune function and related changes in immune indicators, or may provide clues for the discovery of its biomarkers.

Concurrent exercise and metformin administration may reduce the acute and chronic effects of exercise on glucose metabolism in the patients with type 2 diabetes (T2D). However, several studies suggest that combing metformin and exercise treatment may have neither additive effect nor even cause adverse effects in T2D patients. This case report aimed to highlight the challenges associated with prescribing exercise to type 2 diabetes patients undergoing metformin treatment. A 67-years old woman was followed-up for five months, including assessment of the acute and chronic glucose and lactate metabolism induced by concomitant exercise and metformin. The findings were four-fold: 1) During a high-intensity interval training bout, blood glucose systematically decreased, while blood lactate concentrations fluctuated randomly; 2) Basal blood lactate levels were well above 2 mmol/L on days with medication only; 3) Combined exercise and metformin administration induced additive effects on the normalization of glucose and 4) high levels of physical activity had a positive impact on the continuous glucose fluctuations, while decreased levels of physical activity induced a large fluctuation of glucose due to home confinement of an infectious disease caused by the SARS-CoV-2 virus. Our findings showed that when combined with exercise and metformin treatment for T2D patients, exercise may contribute to improving glycemic control while metformin may elevate lactate levels in the long term. The observed results underline the need to prescribe exercise and monitor lactate levels for reducing possible risks associated with metformin treatment and reinforce the importance of tailoring exercise therapy.

Abstract Background Silica-induced pulmonary fibrosis (silicosis) is a diffuse interstitial fibrotic disease characterized by the massive deposition of extracellular matrix in lung tissue. Fibroblast to myofibroblast differentiation is crucial for the disease progression. Inhibiting myofibroblast differentiation may be an effective way for pulmonary fibrosis treatment. Methods The experiments were conducted in TGF-β treated human lung fibroblasts to induce myofibroblast differentiation in vitro and silica treated mice to induce pulmonary fibrosis in vivo. Results By quantitative mass spectrometry, we revealed that proteins involved in mitochondrial folate metabolism were specifically upregulated during myofibroblast differentiation following TGF-β stimulation. The expression level of proteins in mitochondrial folate pathway, MTHFD2 and SLC25A32, negatively regulated myofibroblast differentiation. Moreover, plasma folate concentration was significantly reduced in patients and mice with silicosis. Folate supplementation elevated the expression of MTHFD2 and SLC25A32, alleviated oxidative stress and effectively suppressed myofibroblast differentiation and silica-induced pulmonary fibrosis in mice. Conclusion Our study suggests that mitochondrial folate pathway regulates myofibroblast differentiation and could serve as a potential target for ameliorating silica-induced pulmonary fibrosis.

In this paper, the workability, mechanical, ion leaching, and drying shrinkage properties of alkali-activated concrete with recycled coarse and fine aggregates were studied, and the pore structure and micro-morphology of different alkali-activated recycled aggregate concretes (AARACs) were characterized by using the mercury intrusion method and scanning electron microscopy, respectively. The experimental results showed that with the increase in the replacement rate of the recycled fine aggregate (RFA), the flowability showed a decreasing trend. Adding a certain amount of RFA improves the mechanical properties of the AARAC. The compressive strength at a curing age of 28 days was 65.3 MPa with 70 wt% RFA replacement. When the replacement rate of the RFA was 100 wt%, the maximum splitting tensile strength (4.5 MPa) was obtained at a curing age of 7 days. However, the addition of the RFA had little effect on the flexural strength of the AARAC. As an extension of the curing age, the splitting tensile strength, flexural strength, tension-to-compression ratio, and flexure-to-compression ratio all showed an increasing trend at first and then a decreasing trend. At a curing age of 7 days, the tension-to-compression ratio and flexure-to-compression ratio were both high (except for those of R100), indicating that the ductility and toughness of the specimen were improved. The addition of the RFA increased the drying shrinkage of the AARAC. At a curing age of 120 days, compared to the specimen without the RFA, the drying shrinkage rate of the specimen with the addition of 70 wt% RFA increased by 34.15%. As the curing age increased, the microstructure of the reaction products became denser, but the proportion of large-diameter pores increased. This study evaluated the application of RFA in AARAC. The experimental results showed that the RFA-based AARAC had acceptable mechanical and durability properties.

Mn (Manganese, Mn) is an essential trace element involved in various biological processes such as the regulation of immune, nervous and digestive system functions. However, excessive Mn exposure can lead to immune damage. Occupational workers in cement and ferroalloy manufacturing and other related industries are exposed to low levels of Mn for a long time. Mn exposure is one of the important occupational hazards, but the research on the effect of Mn on the immune system of the occupational population is not complete, and there is no reliable biomarker. Therefore, this study aimed to evaluate the immunotoxicity of Mn from the soluble immune checkpoint TIM-3 (T-cell immunoglobulin and mucin containing protein 3, TIM-3) and complement C3. A total of 144 Mn-exposed workers were recruited from a bus manufacturing company and a railroad company in Henan Province. An inductively coupled plasma mass spectrometer was used to detect the concentration of RBC Mn (Red blood cell Mn, RBC Mn), and ELISA kits were used to detect serum complement C3 and TIM-3. Finally, the subjects were statistically analyzed by dividing them into low and high Mn groups based on the median RBC Mn concentration. We found that Mn exposure resulted in elevated serum TIM-3 expression and decreased complement C3 expression in workers; that serum TIM-3 and complement C3 expression showed a dose–response relationship with RBC Mn; and that the mediating effect of complement C3 between RBC Mn and TIM-3 was found to be significant. The above findings indicate that this study has a preliminary understanding of the effect of Mn exposure on the immune system of the occupational population exposed to Mn, and complement C3 and TIM-3 may be biomarkers of Mn exposure, which may provide clues for the prevention and control of Mn occupational hazards.

Objective To investigate the difference of electroreactivity and electrocoagulation of commonly used interventional materials. Methods The resistance of different types of micro⁃guide wire and spring coil are measured with a multimeter to obtain the physical parameters reflecting the conductivity. The in vitro electrolytic gas production experiment was carried out with physiological saline and isolated arterial blood of New Zealand white rabbits as the medium, the gas production data were obtained, and the thrombus adhesion on the surface of the materials was observed by scanning electron microscopy. Results The resistance measurement results showed ASAHI, SilverSpeed, Traxcess micro⁃guide wire and Axium spring coil have good conductivity, the electrolytic gas production could occur after power⁃up, and the voltage was positively correlated with gas production speed (P＜0.05, for all). The results of in vitro arterial blood electrocoagulation showed that better thrombosis quality could be obtained by increasing the voltage. Conclusions The micro⁃guide wire and spring coil used for intra⁃arterial electrocoagulation can preliminarily selected by resistance measurement, and the voltage is the key factor to determine the electrical reaction intensity and thrombosis quality.

Long-term inhalation of silica particles in the workplace causes silicosis, which is incurable and seriously endangers the health of workers. It is believed that silicosis is caused by an imbalance of the pulmonary immune microenvironment, in which pulmonary phagocytes play a crucial role. As an emerging immunomodulatory factor, it is unclear whether T cell immunoglobulin and mucin domain-containing protein 3 (TIM3) participate in silicosis by modulating pulmonary phagocytes function. The purpose of this study was to investigate the dynamic changes of the TIM-3 in pulmonary macrophages, dendritic cells (DCs), and monocytes during the development of silicosis in mice. The plasma levels of soluble TIM-3 in silicosis patients were also examined. Flow cytometry was used to identify alveolar macrophages (AMs), interstitial macrophages (IMs), CD11b+ DC, CD103+ DC, Ly6C+, and Ly6C- monocytes in mouse lung tissues, and further analyses were conducted on the expression of TIM-3. Results showed that soluble TIM-3 was significantly elevated in plasma of silicosis patients, and the level of which was higher in stage II and III patients than that in stage I. In silicosis mice, the protein and mRNA levels of TIM-3 and Galectin9 were significantly upregulated in lung tissues. Specific to pulmonary phagocytes, silica exposure affected TIM-3 expression in a cell-specific and dynamic manner. In macrophages, TIM-3 expression upregulated in AM after 28 days and 56 days of silica instillation, while the expression of TIM-3 in IM decreased at all observation time points. In DCs, silica exposure only caused a decrease of TIM-3 expression in CD11b+ DCs. In monocytes, TIM-3 dynamics in Ly6C+ and Ly6C- monocytes were generally consistent during silicosis development, which significant decrease after 7 and 28 days of silica exposure. In conclusion, TIM-3 may mediate the development of silicosis by regulating pulmonary phagocytes.

Cement-based material encapsulation is a method of encapsulating electronic devices in highly thermally conductive cement-based materials to improve the heat dissipation performance of electronic components. In the field of construction, a thermoelectric generator (TEG) encapsulated with cement-based materials used in the building envelope has significant potential for waste heat energy recovery. The purpose of this study was to investigate the effect of cement-based materials integrated with aluminum heatsinks on the heat dissipation of the TEG composite structure. In this work, three types of thermoelectric work units encapsulated with cement paste were proposed. Moreover, we explored the effect of encapsulated structure, heat dissipation area, the height of thermoelectric single leg, and heat input temperature on maintaining the temperature difference between the two sides of the thermoelectric single leg with COMSOL Multiphysics. The numerical simulation results showed that under the conditions of a heat source temperature of 313.15 K and ambient temperature of 298.15 K, the temperature difference between the two sides of the internal thermoelectric single leg of Type-III can maintain a stable temperature difference of 7.77 K, which is 32.14% higher than that of Type-I and Type-II (5.88 K), and increased by 26.82% in the actual experiment. This work provides a reference for the selection and application of TEG composite structures of cement-based materials combined with aluminum heatsinks.

The villages on both sides of the canal possess cultural and ecological significance. Applying the concept of environmental culture to the landscape design of the canal countryside plays a crucial role in improving the rural environmental environment and further stimulating rural economic development. Taking the rural areas in Wujiang, China, as an example, this paper integrates the concepts of water culture and ecological culture into the landscape design of the rural regions. Through implementing two significant strategies—ecological landscape construction and flood prevention landscape design. The paper aims to recreate the traditional appearance of villages along the ancient canal. This approach holds practical significance in promoting sustainable rural economic development and maintaining the dynamic balance of rural ecosystems.

Abstract Immunotherapy using programmed cell death 1 (PD1) inhibitors has shown great efficacy in colorectal cancer patients harboring mismatch-repair-deficient (dMMR) and microsatellite instability-high (MSI-H) alterations. We previously showed a negative correlation of zymogen granule protein 16 (ZG16) with programmed death-ligand 1 (PD-L1) expression in patients with colorectal cancer. However, how ZG16 regulates PD-L1 expression is unclear. In this study, we showed that ZG16 can directly bind to glycosylated PD-L1 through its lectin domain, leading to PD-L1 degradation. Mutations on the lectin domain of ZG16 largely inhibit the interaction between ZG16 and PD-L1. Importantly, ZG16 overexpression suppressed tumor growth in two syngeneic mouse models through blockage of PD-L1 expression in cancer cells meanwhile suppression of PD1 expression in T cells. We also showed that ZG16 could improve the effect of chemotherapy and may be delivered as a protein to serve as an immune checkpoint inhibitor to promote T-cell mediated immunity.

Fibrosis is a pathological tissue repair activity in which many myofibroblasts are activated and extracellular matrix are excessively accumulated, leading to the formation of permanent scars and finally organ failure. A variety of organs, including the lung, liver, kidney, heart, and skin, can undergo fibrosis under the stimulation of various exogenous or endogenous pathogenic factors. At present, the pathogenesis of fibrosis is still not fully elucidated, but it is known that the immune system plays a key role in the initiation and progression of fibrosis. Immune checkpoint molecules are key regulators to maintain immune tolerance and homeostasis, among which the programmed cell death protein 1/programmed death ligand 1 (PD-1/PD-L1) axis has attracted much attention. The exciting achievements of tumor immunotherapy targeting PD-1/PD-L1 provide new insights into its use as a therapeutic target for other diseases. In recent years, the role of PD-1/PD-L1 axis in fibrosis has been preliminarily explored, further confirming the close relationship among PD-1/PD-L1 signaling, immune regulation, and fibrosis. This review discusses the structure, expression, function, and regulatory mechanism of PD-1 and PD-L1, and summarizes the research progress of PD-1/PD-L1 signaling in fibrotic diseases.

Abstract Background Lung cancer is one of the cancers with the highest mortality rate in China. With the rapid development of high-throughput sequencing technology and the research and application of deep learning methods in recent years, deep neural networks based on gene expression have become a hot research direction in lung cancer diagnosis in recent years, which provide an effective way of early diagnosis for lung cancer. Thus, building a deep neural network model is of great significance for the early diagnosis of lung cancer. However, the main challenges in mining gene expression datasets are the curse of dimensionality and imbalanced data. The existing methods proposed by some researchers can’t address the problems of high-dimensionality and imbalanced data, because of the overwhelming number of variables measured (genes) versus the small number of samples, which result in poor performance in early diagnosis for lung cancer. Method Given the disadvantages of gene expression data sets with small datasets, high-dimensionality and imbalanced data, this paper proposes a gene selection method based on KL divergence, which selects some genes with higher KL divergence as model features. Then build a deep neural network model using Focal Loss as loss function, at the same time, we use k-fold cross validation method to verify and select the best model, we set the value of k is five in this paper. Result The deep learning model method based on KL divergence gene selection proposed in this paper has an AUC of 0.99 on the validation set. The generalization performance of model is high. Conclusion The deep neural network model based on KL divergence gene selection proposed in this paper is proved to be an accurate and effective method for lung cancer prediction.

After comparing the economic advantages of different methods for energy storage system capacity configuration and hybrid energy storage system (HESS) over single energy storage system, a method based on improved moving average and ensemble empirical mode decomposition (EEMD) to smooth wind power fluctuations is proposed aiming at the optimal capacity configuration of HESS. Firstly, EEMD was used to decompose the HESS reference power which was derived by improved moving average filtering, and then several intrinsic mode functions (IMFs) were obtained. Each IMF instantaneous frequency-time profile was processed by Hilbert transform, the so- call gap frequency was identified, and then reconstruct the high and low frequency components to obtain the HESS reference power. Subsequently, taken the energy storage system charge-discharge efficiency and state of charge (SOC) into account, the rated power and capacities of each scheme was determined. Finally, based on Life Cycle Cost (LCC) theory, an energy storage system economic cost calculation model was established to compare the costs of each scheme and select the optimal one.

Silicosis caused by long-term inhalation of crystalline silica during occupational activities seriously threatens the health of occupational populations. Imbalances in T helper 1(Th1), Th2, Th17, and regulatory T cells (Tregs) promote the development of pulmonary silicosis. Exosomes and their contents, especially microRNAs (miRNAs), represent a new type of intercellular signal transmission mediator related to various diseases including pulmonary fibrosis. However, whether exosomal miRNAs can affect the progression of silicosis by regulating T cell differentiation remains to be determined. To test this hypothesis, we established a miR-125a-5p antagomir mouse model and examined changes in miR-125a-5p levels and T cell subtypes. We found that miR-125a-5p levels were increased in lung tissues and serum exosomes in the silica group at 7 days and 28 days. Downregulation of miR-125a-5p attenuated α-smooth muscle actin (α-SMA), collagen I, fibronectin, p-p65, and p-inhibitor of nuclear factor kappa B (NF-κB) kinase (IKK) protein expression, while tumor necrosis factor receptor-associated factor 6 (TRAF6) and p-inhibitor of κBα (IKBα) expression were increased. MiR-125a-5p anta-miR treatment contributes to the maintenance of Th1/Th2 balance during the progression of pulmonary fibrosis. Our findings indicated that knockdown miR-125a-5p could regulate T lymphocyte subsets and significantly reduce pulmonary fibrosis by targeting TRAF6.

Coke oven emissions (COEs) contain many carcinogenic polycyclic aromatic hydrocarbons (PAHs). Telomere damage is an early biological marker reflecting long-term COEs-exposure. Whereas, whether the genetic variations of telomere-regulated gene TNKS have an effect on the COEs-induced telomere damage is unknown. So we detected the environmental exposure levels, relative telomere length (RTL), and TNKS genetic polymorphisms among 544 COEs-exposure workers and 238 healthy participants. We found that the RTL of the wild homozygous GG genotype in rs1055328 locus was statistically shorter compared with the CG+CC genotype for the healthy participants using covariance analysis(P = 0.008). In the Generalized linear model (GLM) analysis, TNKS rs1055328 GG could accelerate telomere shortening (P = 0.011); and the interaction between TNKS rs1055328 GG and COEs-exposure had an effect on RTL (P = 0.002). In conclusion, this study was the first to discover the role of TNKS rs1055328 locus in COEs-induced telomere damage, and proved that chromosomal damage was a combined consequence of environmental and genetic factors.

Epithelial-mesenchymal transdifferentiation of alveolar type Ⅱ epithelial cells is a vital source of pulmonary myofibroblasts, and myofibroblasts formation is recognized as an important phase in the pathological process of silicosis. miR-30c-5p has been determined to be relevant in the activation of the epithelial-mesenchymal transition (EMT) in numerous disease processes. However, elucidating the role played by miR-30c-5p in the silicosis-associated EMT process remains a great challenge. In this work, based on the establishment of mouse silicosis and A549 cells EMT models, miR-30c-5p was interfered with in vivo and in vitro models to reveal its effects on EMT and autophagy. Moreover, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), connective tissue growth factor (CTGF), autophagy-related gene 5 (ATG5), and autophagy were further interfered with in the A549 cells models to uncover the possible molecular mechanism through which miR-30c-5p inhibits silicosis associated EMT. The results demonstrated the targeted binding of miR-30c-5p to CTGF, ATG5, and MALAT1, and showed that miR-30c-5p could prevent EMT in lung epithelial cells by acting on CTGF and ATG5-associated autophagy, thereby inhibiting the silicosis fibrosis process. Furthermore, we also found that lncRNA MALAT1 might competitively absorb miR-30c-5p and affect the EMT of lung epithelial cells. In a word, interfering with miR-30c-5p and its related molecules (MALAT1, CTGF, and ATG5-associated autophagy) may provide a reference point for the application of silicosis intervention-related targets.

Silicosis, a disease characterized by diffuse fibrosis of the lung tissue, is caused by long-term inhalation of free silica (SiO2) dust in the occupational environment and is currently the most serious occupational diseases of pneumoconiosis. Several studies have suggested that alveolar type Ⅱ epithelial cells (AEC Ⅱ) undergo epithelial-mesenchymal transition (EMT) as one of the crucial components of silicosis in lung fibroblasts. A2aR can play a critical regulatory role in fibrosis-related diseases by modulating the Wnt/β-catenin pathway, but its function in the EMT process of silicosis has not been explained. In this study, an EMT model of A549 cells was established. The results revealed that A2aR expression is reduced in the EMT model. Furthermore, activation of A2aR or suppression of the Wnt/β-catenin pathway reversed the EMT process, while the opposite result was obtained by inhibiting A2aR. In addition, activation of A2aR in a mouse silicosis model inhibited the Wnt/β-catenin pathway and ameliorated the extent of silica-induced lung fibrosis in mice. To sum up, we uncovered that A2aR inhibits fibrosis and the EMT process in silicosis by regulating the Wnt/β-catenin pathway. Our study can provide an experimental basis for elucidating the role of A2aR in the development of silicosis and offer new ideas for further exploration of interventions for silicosis.

Silicosis is an incurable lung disease that can progress even when exposure to silica dust has ended. Lipid metabolism plays an important role in the occurrence and development of silicosis. However, the mechanistic details have not been fully elucidated. This was investigated in the current study by high-performance liquid chromatography-mass spectrometry-based lipidomic analysis of lung tissue in a mouse model of silicosis. Lipid profiles and key metabolic enzymes were compared between silica and control groups. The lipidomic analysis revealed differentially-expressed lipids in the lungs of silicosis mice compared with controls. Among the identified lipid metabolism-related enzymes, the expression of lysophosphatidylcholine acyltransferase 1 (LPCAT1) was significantly down-regulated at the transcript and protein levels. LPCAT1 overexpression in vivo using adeno-associated virus altered the balance between phosphatidylcholine and lysophosphatidylcholine and inhibited the development of silicosis in mice. These results indicate that LPCAT1 dysregulation leads to abnormal lipid metabolism and silicosis, and is a potential therapeutic target for the treatment of silica-induced pulmonary fibrosis.

Commercially wrist-worn devices often present inaccurate estimations of energy expenditure (EE), with large between-device differences. We aimed to assess the validity of the Apple Watch Series 6 (AW), Garmin FENIX 6 (GF) and Huawei Watch GT 2e (HW) in estimating EE during outdoor walking and running. Twenty young normal-weight Chinese adults concurrently wore three index devices randomly positioned at both wrists during walking at 6 km/h and running at 10 km/h for 2 km on a 400- meter track. As a criterion, EE was assessed by indirect calorimetry (COSMED K5). For walking, EE from AW and GF was significantly higher than that obtained by the K5 (p < 0.001 and 0.002, respectively), but not for HW (p = 0.491). The mean absolute percentage error (MAPE) was 19.8% for AW, 32.0% for GF, and 9.9% for HW, respectively. The limits of agreement (LoA) were 44.1, 150.1 and 48.6 kcal for AW, GF, and HW respectively. The intraclass correlation coefficient (ICC) was 0.821, 0.216 and 0.760 for AW, GF, and HW, respectively. For running, EE from AW and GF were significantly higher than the K5 (p < 0.001 and 0.001, respectively), but not for HW (p = 0.946). The MAPE was 24.4%, 21.8% and 11.9% for AW, GF and HW, respectively. LoA were 62.8, 89.4 and 65.6 kcal for AW, GF and HW, respectively. The ICC was 0.741, 0.594, and 0.698 for AW, GF and HW, respectively. The results indicate that the tested smartwatches show a moderate validity in EE estimations for outdoor walking and running.

The water–cement ratio (w/c) has a significant effect on the strength of recycled concrete. In this study, considering the effects of water/cement ratio, strength, and water content of recycled aggregates, two kinds of pulse sequences of low-field nuclear magnetic resonance (LF-NMR) were applied to investigate the water migration behavior between simulated recycled aggregates (SRA) and water or fresh mortar. Three sets of concrete strength tests were designed and the results were used to verify the findings of LF-NMR imaging tests. The results showed that the depth of water migration in the SRA increases with time: at first the change rate is rapid, then slows down, and eventually tends to remain stable. When the SRA is in contact with fresh mortar with low w/c, no water migration occurs because the hydration of the cement in the mixture consumes a large amount of water, resulting in the inability of water to migrate into the SRA through capillary pressure. For the recycled aggregate concrete with high strength, the addition of extra water will increase the effective w/c and reduce the compressive strength of the concrete.

Objective To explore the epidemiological status and related factors for comorbidities of osteoarthritis (OA) among adult residents in Beijing. Methods Based on the medical records of all designated medical institutes in Beijing from 2015 to 2017, relevant data of adult OA patients were collected, and the prevalence of major comorbidities such as type 2 diabetes, depression, hypertension and dyslipidemia in this population was statistically described and analyzed, and the differences among populations with different sociodemographic characteristics were compared. Results A total of 3 048 304 adult OA patients were included, with a mean age of 58.2±14.5 years, and females accounting for 62.2%. 79.8% of the subjects had at least 1 comorbidity, with the males (82.6%) having a higher prevalence than the females (78.1%). The prevalence of OA comorbidities was increased with age and statistically significant among different age groups (P < 0.05). The prevalence in the patients living in the rural areas (82.7%) was higher than that in urban areas (78.8%). The top 4 most common comorbidities were hypertension (68.0%), dyslipidemia (63.8%), type 2 diabetes (36.3%), and depression (8.2%). The males were more likely to suffer from hypertension, dyslipidemia and type 2 diabetes, while the females from depression. The proportion of OA patients with 1, 2, 3 or more kinds of comorbidities was 17.7%, 30.7%, 31.4% respectively. The risk factors for OA comorbidities included: male (OR=1.15, 95%CI: 1.14~1.16), ≥55 years old (OR=1.07, 95%CI: 1.07~1.07), living in rural areas (OR=1.66, 95%CI: 1.64~1.67), and taking manual labor (OR=1.02, 95%CI: 1.01~1.02). Conclusion The adult OA patients in Beijing have relatively high prevalences of comorbidities, including dyslipidemia, hypertension, type 2 diabetes and other diseases. More attention should be paid to the middle-aged and elderly patients and those in rural areas.

Objective To investigate the correlation of metabolic syndrome (MS) and its components with arterial stiffness, and to analyze the gender difference. Methods Questionnaires, physical examinations and blood biochemical tests were conducted among 6 737 rural residents in Beijing. The diagnosis of MS is identified based on the 2017 modified standard of Diabetes Society of Chinese Medical Association, and arterial stiffness is defined as brachia-ankle pulse wave velocity (BAPWV) ≥1 700 cm/s. Multivariate Logistic regression analysis was used to analyze the correlation of MS and its components with arterial stiffness. Results In the subjects, arterial stiffness and MS patients accounted for 41.7% and 64.4%, respectively. The MS patients was at a risk of arterial stiffness by 2.36-fold (95%CI: 2.06~2.71) higher than that in the non-MS subjects. Except for the reduced high density lipoprotein-cholesterol (HDL-C), the other MS components were all significantly correlated with arterial stiffness, including elevated blood pressure, blood glucose and triglyceride, and central obesity. The correlation between MS and arterial stiffness was stronger in the women than the men. Conclusion MS is correlated with an increased risk of arterial stiffness, with elevated blood pressure being the most significant component. The effect of MS and its components on arterial stiffness is stronger in female population.

Objective To investigate the epidemiological status and characteristics of common comorbidities among patients with type 2 diabetes mellitus (T2DM) in Beijing. Methods A total of 1 156 965 patients diagnosed with T2DM in 2017 in Beijing were recruited, and their outpatient and inpatient records at all levels of hospitals from 2016 to 2017 were collated and analyzed. The prevalence of 9 comorbidities in this population was described, including hypertension, ischemic heart disease, stroke, lung cancer, chronic kidney disease, severe hearing loss, depression, retinopathy and obstructive pulmonary disease. The differences among different genders and age groups were subsequently compared. Results The enrolled patients were at a mean age of 61.28±13.14 years, and the males accounted for 51.93%. Of them, 29.02% had at least 1 comorbidity. The prevalence of comorbidities was increased with age, and the females had a higher prevalence of comorbidities than the males (P < 0.01). The 4 major comorbidities with the highest prevalence were hypertension (20.16%), depression (6.15%), ischemic heart disease (3.52%) and stroke (3.27%) in order. The females were more likely to suffer from hypertension and depression (P < 0.01), while the males from ischemic heart disease, stroke, obstructive lung disease, lung cancer and chronic kidney disease (P < 0.01). The percentage of patients with 2 or more kinds of comorbidities accounted for 4.59%. The most commonly combined 2 diseases were hypertension with depression (1.75%), hypertension with stroke (1.25%), and hypertension with ischemic heart disease (1.16%). The most common comorbidities were hypertension and stroke in the males (1.51%), and hypertension and depression in the females (2.12%). Conclusion T2DM patients are prone to cardiovascular and metabolic diseases as well as depression. The females are more likely to be accompanied with hypertension and depression, while the males with diseases of other systems and organs, and have relatively poor prognosis.

Under the strategies of low-carbon and environmental protection, promoting green technology innovation to achieve carbon neutrality in the construction field has become a universal goal. As the building material with the highest consumption, concrete has gradually begun to transform into a multi-functional and intelligent product. Therefore, the research on carbon fiber-reinforced cement-based composites (CFRCs) is of relative interest. It mainly uses carbon fibers (CFs) with high elasticity, strength, and conductivity to disperse evenly into the concrete as a functional filler, to achieve the intelligent integration of concrete structures and function innovatively. Furthermore, the electrical conductivity of CFRC is not only related to the content of CFs and environmental factors but also largely depends on the uniform dispersion and the interfacial bonding strength of CFs in cement paste. This work systematically presents a review of the current research status of the enhancement and modification mechanism of CFRC and the evaluation methods of CF dispersion. Moreover, it further discusses the improvement effects of different strengthening mechanisms on the mechanical properties, durability, and smart properties (thermoelectric effect, electrothermal effect, strain-sensitive effect) of CFRC, as well as the application feasibility of CFRC in structural real-time health monitoring, thermal energy harvesting, intelligent deformation adjustment, and other fields. Furthermore, this paper summarizes the problems and challenges faced in the efficient and large-scale applications of CFRCs in civil engineering structures, and accordingly promotes some proposals for future research.

Objective To investigate the clinical efficacy of cevimeline as a pharmacotherapeutic approach to stimulating gland activity in improving the symptoms and signs of primary Sjögren syndrome (pSS). Methods Sixty-three patients diagnosed with pSS who attended the Affiliated Huai'an Hospital of Xuzhou Medical University from January 2018 to September 2019 were included in this trial. They were randomly assigned to the therapeutic group and control group. All patients were recalled at baseline and after 2 weeks, 3 months and 6 months. Measurement of salivary and lacrimal flow as well as evaluation of subjective symptoms was performed at the follow-up. Results Fifty-eight patients completed the trial and were included in the statistical analysis. There was a significant difference between the two groups in the measurement of salivary and lacrimal flow at the second week and third month (P < 0.05). Improvement in subjective symptoms of oral, ocular and gland was detected at the third month (P < 0.05). At the sixth month, compared with the control group, only the salivary gland symptom score of the treatment group was statistically significant (P < 0.05). Conclusion Cevimeline has good specificity and safety and can increase salivary and lacrimal flow and improve subjective symptoms of pSS in a short time.

Pulmonary fibrosis induced by silica particles is defined as silicosis, which is an incurable disease. The pathogenesis of silicosis is not completely clear, but it’s certain that immune system dysfunction is closely related to it. Immune checkpoint inhibitors (ICIs) are emerging immunotherapeutic agents that mainly target adaptive immune cells, and there is abundant evidence that ICIs are of great value in cancer treatment. However, whether these attractive agents can be implemented in silicosis treatment is unclear. In this study, we explored the efficacy of small molecule inhibitors targeted PD-1/PD-L1 and CTLA-4 on silica-induced pulmonary fibrosis in mice. ICIs were injected intraperitoneally into mice that received silica instillation twice a week. The mice were sacrificed 7 and 28 days after the injection. The lungs, spleen, hilar lymph nodes, thymus, and peripheral blood of mice were collected and subjected to histological examination, flow cytometry analysis, and mRNA and protein quantification. Our results demonstrated that silica exposure caused damage to multiple immune organs in mice, leading to an imbalance in systemic immune homeostasis. Specifically, proportions and subtypes of T and B cells were significantly altered, and the expressions of PD-1, PD-L1 and CTLA-4 were abnormal on these cells. Both PD-1/PD-L1 and CTLA-4 inhibitor administration modulated silica-induced immune system disruption, however, only PD-1/PD-L1 signaling inhibition showed significant amelioration of silicosis. Our findings confirmed for the first time the potential value of ICIs for the treatment of silica-induced pulmonary fibrosis, and this may provide new ideas for the treatment of other fibrosis-related diseases.

In this paper, recycled concrete powder (RCP) is used as the carrier of g-C3N4-TiO2 instead of natural minerals. The prepared g-C3N4-TiO2/RCP composites were characterized by X-ray diffractometer, scanning electron microscope, infrared spectrometer, specific surface area analyzer, UV-visible spectrophotometer, and RhB solution degradation experiments. The results show that the rough, porous structure of RCP was beneficial to the stable load of g-C3N4-TiO2. Under the condition that the content of g-C3N4-TiO2 catalyst is constant, the agglomeration of g-C3N4-TiO2 can be reduced by using RCP as a carrier, thus improving its photocatalytic efficiency. Subsequently, g-C3N4-TiO2/RCP was loaded onto the surface of cement-based materials by coating bonding method to study its photocatalytic performance. It is found that the photocatalytic cement-based material has a similar degradation effect on the degradation of surface RhB as g-C3N4-TiO2/RCP in RhB solution. Our work may open up a new field for the recycling of RCP and provide new ideas for the development of photocatalytic cement-based materials.

This paper discusses the latest progress in research on ant nests and explores innovative scientific concepts associated with underground ant nests from the perspective of bionics. The methods used by scholars to study the structure of ant nests and the interaction between the structure itself and the individual ants are investigated. The structural characteristics of the ant nest, its internal environment and ventilation characteristics are discussed in detail. In addition, this paper presents an innovative project in which the effect of underground ant nests on soil geotechnical properties and the effect of calcined ant nest soil powder, from the perspective of civil engineering, are addressed. Practical examples of the application of the structural and inter-relational aspects of subterranean ant nests in the field of architectural bionics are also provided, from the perspectives of construction, morphology, function and material. This review attempts to integrate civil engineering, architecture and biology, enlighten architects and biologists on converging their thinking, provide new ideas regarding underground ant colony nests, and provide references for long-term human habitation.

Telomeres are functional complexes at the ends of linear chromosomes, and telomerase aids in their maintenance and replication. Additionally, accumulating evidence suggests that telomerase-associated protein 1 (TEP1) is a component of the telomerase ribonucleoprotein complex and is responsible for catalyzing the addition of new synthetic telomere sequences to chromosome ends. In our previous study, we found that genetic variants of the TERT gene participated in the regulation of telomere length. Exposure to particulate matter, environmental pollutants, oxidative stress, and pesticides is associated with shortening of telomere length. However, it is unknown whether genetic variants in the TEP1 gene may affect telomere length (TL) in polycyclic aromatic hydrocarbon (PAH)-exposed workers. Therefore, we measured the peripheral leukocyte TL and genotyped the polymorphism loci in the TEP1 gene among 544 PAH-exposed workers and 238 healthy controls. Covariance analysis showed that the individuals carrying TEP1 rs1760903 CC and TEP1 rs1760904 TT had longer TL in the control group (P

Exposure to sensitizer has been suggested to be hazardous to human health, evaluation the sensitization of sensitizer is particularly important and urgently needed. Dendritic cells (DCs) exert an irreplaceable function in immunity, and the T cell receptor (TCR) repertoire is key to ensuring immune response to foreign antigens. We hypothesized that a co-culture model of human monocyte-derived dendritic cells (Mo-DCs) and T cells could be employed to evaluate the sensitization of DNCB. An experimental model of DNCB-induced sensitization in rat was employed to examine alterations of cluster of differentiation CD103+ DCs and T cells. A co-cultured model of Mo-DCs and T cells was developed in vitro to assess the sensitization of DNCB through the phenotypic and functional alterations of Mo-DCs, as well as the TCR repertoire. We found that the CD103+ DCs phenotype and T-helper (Th) cells polarization altered in sensitization rats. In vitro, phenotypic alteration of Mo-DCs caused by DNCB were consistent with in vivo results, antigen uptake capacity of Mo-DCs diminished and capacity of Mo-DCs to prime T cell increased. Clones of the TCR repertoire and the diversity of TCR repertoire were enhanced, changes were noted in the usage of variable, joining, and variable-joining gene combinations. DNCB exposure potentiated alterations and characteristics of Mo-DCs and the TCR repertoire in a co-culture model. Such changes provided innovative ideas for evaluating sensitization of DNCB.

Abstract Background Polycyclic aromatic hydrocarbons (PAHs) exposure had been reported to be a risk factor of mtDNAcn in our early study. However, the effect of metabolic enzymes' genetic polymorphisms on mtDNAcn in PAHs‐Exposure workers has not been fully evaluated. Aim The aim of the study was to explore the effect of metabolic enzymes' genetic polymorphisms on mtDNAcn in PAHs‐Exposure. Methods and Results We investigated the effects of metabolic enzymes' genetic polymorphisms on mtDNAcn among 544 coke oven workers and 238 office staffs. The mtDNAcn of peripheral blood leukocytes was measured using the Real‐time quantitative polymerase chain reaction (PCR) method. PCR and restriction fragment length was used to detect five polymorphisms in GSTT1, GSTM1, GSTP1 rs1695, CYP2E1 rs6413432, and CYP2E1 rs3813867. The mtDNAcn in peripheral blood leukocytes was significantly lower in the exposure group than that in the control group (p

This study aimed to investigate the effect of bone marrow-derived mesenchymal stem cells (BMSCs) on silica-induced lung fibrosis in a rat model. Thirty SD rats were randomly divided into three groups: control group, silica group, and BMSC group (n = 10 rats per group). BMSCs were injected successively into rats on the 14th, 28th, and 42nd days after silica exposure. All rats were sacrificed 56 days after silica exposure. We detected the pathological and fibrotic changes, apoptosis, autophagy, and pyroptosis in their lung tissue by histopathological examination, hydroxyproline content assays, real-time quantitative polymerase chain reactions, western blot assays, immunohistochemistry staining, immunofluorescence staining, and enzyme-linked immunosorbent assays. We found that BMSCs significantly relieved lung inflammatory infiltrates, collagen deposition, hydroxyproline content, and the mRNA and protein levels of collagen 1 and fibronectin. Compared to the silica group, in the BMSC group, apoptosis-associated proteins, including cleaved caspase 3 and Bax, were significantly downregulated, and Bcl-2/Bax was significantly upregulated; pyroptosis-related proteins, including Nlrp3, cleaved caspase 1, IL-1β, and IL-18, were significantly reduced. However, the BMSCs had no significant impact on autophagy-related proteins, including Beclin 1, P62, and LC3. In summary, BMSCs protected lung tissue against severe fibrosis by inhibiting apoptosis and pyroptosis but not autophagy.

Abstract Background Inflammatory micro-environment has been proposed to play a critical role in lung tumorigenesis. NLRP3 is known as an intracellular receptor involving inflammation and has been reported which is increasingly associated with tumor development, but the role in inflammation-driven lung cancer has not been fully clarified. In this study, we investigated whether lipopolysaccharide (LPS)-induced pulmonary inflammation could contribute to lung tumorigenesis induced by benzo(a)pyrene [B(a)p] in C57BL/6J mice and the role of NLRP3 in the pathogenesis. Methods NLRP3−/− mice and C57BL/6J mice (wide-type, WT) were instilled intratracheally with B(a)p (1 mg/mouse) once a week for 4 times [the week of the last time of B(a)p treatment named Week 0], and mice were then instilled intratracheally with LPS at Week 3, 2.5 μg/mouse, once every three weeks for 5 times. At Week 30, the incidence, number, size and histopathology of lung tumor were analyzed. Results Mice exposed to B(a)p or B(a)p plus LPS could induce lung tumors, whereas LPS or vehicles treatment could not induce lung tumorigenesis. In WT mice, B(a)p plus LPS exposure significantly increased tumor incidence, mean tumor count and tumor size of visible tumors of lungs compared with B(a)p treatment alone, and NLRP3 deletion inhibited lung tumorigenesis induced by B(a)p or B(a)p plus LPS. Histopathological examination found LPS-induced pulmonary inflammatory changes enhanced lung tumorigenesis induced by B(a)p in WT mice, deletion of NLRP3 improved the inflammatory changes induced by LPS and the number and size of pathological tumor nests induced by B(a)p or B(a)p plus LPS. In addition, we found B(a)p treatment and B(a)p plus LPS treatment predominately induced the development of adenoma. Conclusion LPS enhanced B(a)p-induced lung tumorigenesis in WT and NLRP3−/− mice of C57BL/6J strain, and NLRP3 deletion inhibits lung tumorigenesis induced by B(a)p or B(a)p plus LPS.

A two-step method was used to load TiO2 on a cement matrix, and zeolite was chosen as intermediate support. TiO2@Zeolite composite coated photocatalytic cement-based material (PCM) was prepared. Some advanced characterization technologies including X-ray diffraction (XRD), scanning electronic microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), and BET specific surface area (SSA) test were applied to characterize the physicochemical properties of as-prepared PCM. Photocatalytic degradation of trichloroacetamide (TCAcAm) was conducted to evaluate its photocatalytic efficiency. Results show that TiO2@Zeolite composite can improve the adsorption ability of PCM and TiO2 particles were dispersed on the surface of PCM homogeneously providing abundant active sites for photocatalytic reactions. Moreover, TiO2@Zeolite composite can reduce the negative effect of cement on TiO2. The synergetic effect of TiO2@Zeolite composite can remarkably improve the photocatalytic degradation rate, reaching up to 97.8%. TiO2@Zeolite composite coated PCM holds great promise to eliminate water pollution.

Abstract Background Depressive symptoms and cognitive impairment often coexisted in the elderly. This study investigates the effect of late-life depressive symptoms on risk of mild cognitive impairment (MCI). Methods A total of 14,231 dementia- and MCI free participants aged 60+ from the Survey of Health, Ageing, and Retirement in Europe were followed-up for 10 years to detect incident MCI. MCI was defined as 1.5 standard deviation (SD) below the mean of the standardized global cognition score. Depressive symptoms were assessed by a 12-item Europe-depression scale (EURO-D). Severity of depressive symptoms was grouped as: no/minimal (score 0–3), moderate (score 4–5), and severe (score 6–12). Significant depressive symptoms (SDSs) were defined as EURO-D score ≥ 4. Results During an average of 8.2 (SD = 2.4)-year follow-up, 1,352 (9.50%) incident MCI cases were identified. SDSs were related to higher MCI risk (hazard ratio [HR] = 1.26, 95% confidence intervals [CI]: 1.10–1.44) in total population, individuals aged 70+ (HR = 1.35, 95% CI: 1.14–1.61) and women (HR = 1.28, 95% CI: 1.08–1.51) in Cox proportional hazard model adjusting for confounders. In addition, there was a dose–response association between the severity of depressive symptoms and MCI incidence in total population, people aged ≥70 years and women (p-trend

Idiopathic pulmonary fibrosis (IPF) is a chronic, fatal disease with high mortality and poor prognosis. It is characterized by a gradual decline in lung function, and there are currently no effective therapeutic methods. Folate is a water-soluble B vitamin that plays an important role in one-carbon transfer reactions, nucleic acid biosynthesis and methylation reactions. Studies have shown that folate may participate in the pathogenesis of IPF through ways of DNA repair, methylation, and reactive oxygen species. Macrophage activation is an important early cellular event in IPF and the inflammatory response that they trigger is a significant feature of IPF. Folate receptor-β (FR-β) is a cell surface glycosylphosphatidylinositol-anchored glycoprotein that can mediate the unidirectional transport of folate into cells. And it has been found in previous studies that FR-β is usually overexpressed on activated macrophages, but the expression on resting macrophages was undetectable. Therefore, targeting FR-β may have potential value for the early diagnosis and therapy of IPF. Our goal is to highlight the biological role of folate and FR-β in IPF, and we hope to provide helpful insight for clinical treatment strategies.

High-dose cyclophosphamide (CTX) inhibits the immune response. Dendritic cells (DCs) are professional antigen presenting cells (APCs) with a crucial role in initiating immune responses and sustaining immune tolerance. The relative contribution of DCs to immunosuppression induced by high-dose CTX is not well-documented. In this study, we employed the CTX-induced immunosuppressive rat model to examine alterations in DCs. We generated and cultured monocyte-derived immature DCs (imDCs) in vitro and explored their capacity of antigen uptake, T cell priming, cytokine production, and surface marker expression following high-dose CTX. Subsequently, we co-cultured CTX-treated imDCs with Th cells to determine Th cell polarization, and further explored the Toll-like receptor/Myeloid differentiation primary response 88/Mitogen-activated protein kinase (TLR/MyD88/MAPK) pathway. Our results show reduced cell number and surface maker alterations in splenic CD103+ DCs of CTX-treated immunosuppressed rats. In vitro, high-dose CTX weakened the antigen uptake capacity and enhanced the T cell priming capacity of imDCs, in addition to triggering imDC surface marker alterations. TLR, MyD88, and MAPK expression levels, involved in mediating Th cell polarization, were also significantly elevated. Our collective findings indicate that high-dose CTX administration potentiates phenotypic and functional alterations of imDC. Such changes may contribute to the regulation of Th polarization.

The effects of dolomite powder on the freeze–thaw resistance of C30 and C45 concrete were investigated in this manuscript. Scanning electron microscopy (SEM), the electric flux method, and a freeze–thaw cycle testing machine were used to determine the morphology, chloride penetration resistance, mass loss rate, and relative dynamic elastic modulus (Er) of concrete incorporating dolomite powder. Concrete’s freeze–thaw resistance improved as the dosage of dolomite powder was increased. After 300 cycles, the mass loss rates of reference specimens of C30 and C45 concrete were 6.71% and 0.14%, respectively, whereas the mass loss rates of C30 and C45 concrete in the presence of dolomite powder at a 50% replacement level were 5.81% and 0.13%, respectively. After 225 cycles, the Er of C30 concrete was 42.57% and 48.56% in the case of dolomite powder at 0 and 50% replacement levels, respectively. Meanwhile, after 300 cycles, the Er of C45 concrete was 67.54% and 71.50% in the case of dolomite powder at 0 and 50% replacement levels, respectively. Accordingly, the structure of dolomite-containing cement-based materials became more compact. Based on the Weibull distribution, a damage model for concrete containing dolomite powder was proposed. It established that concrete treated with dolomite powder had a lower degree of damage than reference specimens when subjected to the same freeze–thaw conditions.