Improve the Crosslinking Reactivity of Nitrile: Design of Nitrile-Functionalized Pyrazine and its Hydrogen Bond-Assisted Nucleophilic Enhancement Study.

In this study, molecular engineering and biomimetic principles are utilized to prepare highly effective nitrile-functionalized pyrazine crosslinking units by exploiting pyrazine's unique nucleophilic strengthening mechanism and proton bonding ability. The curing behaviors of pyrazine-2,3-dicarbonitrile and phthalonitrile are investigated through model curing systems and molecular simulation. The results indicate that pyrazine-2,3-dicarbonitrile exhibits higher reactivity than phthalonitrile, promoted by amine. The cured products of pyrazine-2,3-dicarbonitrile predominantly comprise thermally stable azaisoindoline and azaphthalocyanine. This novel type of highly effective crosslinking unit, and the comprehended mechanism of action of pyrazine at the molecular level, significantly expand the application of pyrazine in materials science.

Atrazine exposure triggers common carp neutrophil apoptosis via the CYP450s/ROS pathway.

Due to the excessive pursuit of crop yields and the abuse of herbicides, water pollution caused by atrazine (ATR) has become one of the most severe environmental issues threatening the health of fish and aquatic animals. However, no detailed report has been conducted on the mechanisms of ATR immunotoxicity in fish neutrophils. To investigate these mechanism, we exposed peripheral blood neutrophils to 25 µg/ml atrazine for 1, 2, and 3 h. The results showed that ATR induced the mRNA expression of CYPs enzymes (CYP1A1, CYP1B1, CYP1C and CYP3A138), which increased the ROS levels, and inhibited the SOD and CAT activities, GSH content and spurred the accumulation of MDA. Additionally, a significant decline in the OXPHOS, Na+-K+-ATPase and Ca2+-Mg2+-ATPase activities of mitochondria was observed after ATR exposure. Concurrently, ATR activated Caspase3 and induced apoptosis by changing the expression of mitochondrial pathway factors (Bcl-2, BAX, Caspase9) and death receptor pathway major genes (TNF-α, TNFR, Fas, FasL, and Caspase8). The results reported here indicate that the oxidative stress and mitochondrial damage caused by ATR metabolism may play a crucial role in the apoptosis of carp neutrophils, and enrich the immunotoxicological mechanisms of ATR observed in fish.

Selenoprotein S silencing triggers mouse hepatoma cells apoptosis and necrosis involving in intracellular calcium imbalance and ROS-mPTP-ATP.

Selenoprotein S (SelenoS) is one of the cellular endoplasmic reticulum (ER) and membrane located selenoproteins, and it has the main functions of anti-oxidation, anti-apoptosis and anti-ER stress. To investigate the effect of SelenoS silencing on mouse hepatoma cell death and the intracellular biological function of SelenoS, we knocked down SelenoS in Hepa1-6 cells, and detected ER stress, intracellular calcium homeostasis, mitochondrial dynamics, apoptosis and necrosis. To further explore whether reactive oxygen species (ROS) has an effect on apoptosis and necrosis under SelenoS silencing, we used NAC (2.5 mM) to pretreat cells, and detected ΔΨm, ATP, and apoptosis and necrosis rates. SelenoS silencing broke the intracellular calcium homeostasis, induced mitochondrial dynamic disorder, ROS accumulation, loss of ΔΨm and ATP, and triggered apoptosis and necrosis in mouse hepatoma cells. The clearance of ROS alleviated the loss of ΔΨm and ATP caused by silencing of SelenoS, reduced cell necrosis and increased apoptosis. However, SelenoS silencing did not cause ER stress in Hepa1-6 cells. These results indicate that SelenoS silencing triggers mouse hepatoma cells apoptosis and necrosis through affecting intracellular calcium homeostasis and ROS-mPTP-ATP participates in cell death transformation from apoptosis to necrosis to rise damage.

Selenium antagonizes cadmium-induced apoptosis in chicken spleen but not involving Nrf2-regulated antioxidant response.

The nuclear transcription factor NF-E2-related factor 2 (Nrf2) binds to antioxidant response elements (AREs) and is involved in the regulation of genes participated in defending cells against oxidative damage, which have been confirmed in animal models. Selenium (Se), known as an important element in the regulation of antioxidant activity, can antagonize Cadmium (Cd) toxicity in birds. However, the role of Nrf2 in selenium-cadmium interaction has not been reported in birds. To further explore the mechanism of selenium attenuating spleen toxicity induced by cadmium in chickens, cadmium chloride (CdCl2, 150mg/kg) and sodium selenite (Na2SeO3, 2mg/kg) were co-administrated or individually administered in the diet of chickens for 90 days. The results showed that Cd exposure increased the level of hydrogen peroxide (H2O2) and malondialdehyde (MDA) and decreased the antioxidant enzyme activities, including superoxide dismutase (SOD), glutathione peroxidase (Gpx), total antioxidative capacity (T-AOC), catalase (CAT). Cd exposure increased obviously nuclear accumulation of Nrf2, and the expression of Nrf2 downstream heme oxygenase-1 (HO-1) and NAD(P)H: quinine oxidoreductase 1 (NQO1), reduced the expression of Kelch-like ECH-associated protein (keap1), Gpx-1 and thioredoxin reductase-1 (TrxR1). In addition, Cd induced the increase of bak, caspase9, p53, Cyt c mRNA levels, increased bax/bcl-2 ratio, increased caspase3 mRNA and protein levels. Selenium treatment reduced the accumulation of Cd in the spleen, attenuates Cd-induced Nrf2 nuclear accumulation, enhanced antioxidant enzyme activities, ameliorated Cd-induced oxidative stress and apoptosis in the spleen. In summary, our results demonstrate that Se ameliorated spleen toxicity induced by cadmium by modulating the antioxidant system, independently of Nrf2-regulated antioxidant response pathway.

Effects of selenium-lead interaction on the gene expression of inflammatory factors and selenoproteins in chicken neutrophils.

Lead (Pb) is one of the most highly toxic metal pollutant that can cause damage to the immune system. It is known that selenium (Se) can antagonize heavy metals. To explore the toxic effects of Pb poisoning on bird immune cells, as well as the alleviating effects of Se on Pb, Se supplement and/or Pb poisoning chicken models were established. One hundred and eighty Hyline 7-day-old male chickens received either Se (1mg Se per kg of diet), Pb (350mg Pb per liter water) or Se+Pb in their diet and water for 90 days. Then, whole blood was collected from the four groups of chickens, and serum and neutrophils were isolated. The levels of Se and Pb in chicken serum, mRNA levels of 24 selenoproteins (GPX1, GPX2, GPX3, GPX4, Dio1, Dio2, Dio3, Txnrd1, Txnrd2, Txnrd3, SELS, SPS2, SELK, SELW1, SEP15, SEPX1, SELT, SELI, SELO, SELM, SEPN1, SEPP1, SELU, SELH) and inflammatory factors (TNF-α, COX-2, iNOS, NF-κB), and iNOS protein level in chicken neutrophils were determined, and protein-protein interaction prediction and principal component analysis were performed. The data showed that Pb exposure increased Pb content in serum, activated the NF-κB pathway, and increased the expression of selenoproteins in chicken neutrophils. Se supplements could reduce Pb concentration in serum, had a mitigative effect on the activation of the NF-κB pathway and further enhanced the upward trend of selenoprotein expression induced by Pb exposure. These results suggest that Se supplement could eliminate Pb in serum and alleviate the activation of the NF-κB pathway under Pb exposure by increasing the expression of selenoproteins.

The study of the optimal parameter settings in a hospital supply chain system in Taiwan.

This study proposed the optimal parameter settings for the hospital supply chain system (HSCS) when either the total system cost (TSC) or patient safety level (PSL) (or both simultaneously) was considered as the measure of the HSCS's performance. Four parameters were considered in the HSCS: safety stock, maximum inventory level, transportation capacity, and the reliability of the HSCS. A full-factor experimental design was used to simulate an HSCS for the purpose of collecting data. The response surface method (RSM) was used to construct the regression model, and a genetic algorithm (GA) was applied to obtain the optimal parameter settings for the HSCS. The results show that the best method of obtaining the optimal parameter settings for the HSCS is the simultaneous consideration of both the TSC and the PSL to measure performance. Also, the results of sensitivity analysis based on the optimal parameter settings were used to derive adjustable strategies for the decision-makers.

Biomineralization-Inspired Confined-Space Fabrication of Polyimide Aerogels.

The biomineralization process endows biominerals with unique hierarchically porous structures and physical-chemical properties by filling the restricted microreaction space with amorphous phases before the growth of inorganic crystals. In this paper, a confined-space fabrication method inspired by biomineralization for preparing hierarchically porous polyimide (PI) aerogels and PI-derived carbon aerogels is introduced. The confined structure is established through a self-assembly method of vacuum impregnation and ultrasound-assisted freeze-drying. The hierarchically porous structure is controlled by adjusting the structure characteristics of the confined space and secondary aerogels. Subsequently, a variety of performance demonstrations are conducted to demonstrate the mechanical properties and application prospects in the fields of thermal insulation and electromagnetic shielding of the prepared aerogel.

PEEK for Oral Applications: Recent Advances in Mechanical and Adhesive Properties.

Polyetheretherketone (PEEK) is a thermoplastic material widely used in engineering applications due to its good biomechanical properties and high temperature stability. Compared to traditional metal and ceramic dental materials, PEEK dental implants exhibit less stress shielding, thus better matching the mechanical properties of bone. As a promising medical material, PEEK can be used as implant abutments, removable and fixed prostheses, and maxillofacial prostheses. It can be blended with materials such as fibers and ceramics to improve its mechanical strength for better clinical dental applications. Compared to conventional pressed and CAD/CAM milling fabrication, 3D-printed PEEK exhibits excellent flexural and tensile strength and parameters such as printing temperature and speed can affect its mechanical properties. However, the bioinert nature of PEEK can make adhesive bonding difficult. The bond strength can be improved by roughening or introducing functional groups on the PEEK surface by sandblasting, acid etching, plasma treatment, laser treatment, and adhesive systems. This paper provides a comprehensive overview of the research progress on the mechanical properties of PEEK for dental applications in the context of specific applications, composites, and their preparation processes. In addition, the research on the adhesive properties of PEEK over the past few years is highlighted. Thus, this review aims to build a conceptual and practical toolkit for the study of the mechanical and adhesive properties of PEEK materials. More importantly, it provides a rationale and a general new basis for the application of PEEK in the dental field.

Tween-20-Modified BiVO4 Nanorods for CT Imaging-Guided Radiotherapy of Tumor.

Oral cancer is the most common malignant tumor in the oral and maxillofacial region, which seriously threatens the health of patients. At present, radiotherapy is one of the commonly used methods for oral cancer treatment. However, the resistance of cancerous tissues to ionizing radiation, as well as the side effects of X-rays on healthy tissues, still limit the application of radiotherapy. Therefore, how to effectively solve the above problems is still a challenge at present. Generally speaking, elements with high atomic numbers, such as bismuth, tungsten, and iodine, have a high X-ray attenuation capacity. Using nanomaterials containing these elements as radiosensitizers can greatly improve the radiotherapy effect. At the same time, the modification of nanomaterials based on the above elements with the biocompatible polymer can effectively reduce the side effects of radiosensitizers, providing a new method for the realization of efficient and safe radiotherapy for oral cancer. In this work, we prepared Tween-20-modified BiVO4 nanorods (Tw20-BiVO4 NRs) and further used them in the radiotherapy of human tongue squamous cell carcinoma. Tw20-BiVO4 NRs are promising radiosensitizers, which can generate a large number of free radicals under X-rays, leading to the damage of cancer cells and thus playing a role in tumor therapy. In cell experiments, radiotherapy sensitization of Tw20-BiVO4 NRs significantly enhanced the production of free radicals in oral cancer cells, aggravated the destruction of chromosomes, and improved the therapeutic effect of radiotherapy. In animal experiments, the strong X-ray absorption ability of Tw20-BiVO4 NRs makes them effective contrast agents in computed tomography (CT) imaging. After the tumors are located by CT imaging, it helps to apply precise radiotherapy; the growth of subcutaneous tumors in nude mice was significantly inhibited, confirming the remarkable effect of CT imaging-guided radiotherapy.

PVP-Modified Multifunctional Bi2WO6 Nanosheets for Enhanced CT Imaging and Cancer Radiotherapy.

Malignant tumors are one of the main causes of human death. The clinical treatment of malignant tumors is usually surgery, chemotherapy, radiotherapy, and so forth. Radiotherapy, as a traditional and effective treatment method for cancer, is widely used in clinical practice, but the radiation resistance of tumor cells and the toxic side effects to normal cells are still the Achilles heel of radiotherapy. Multifunctional inorganic high-atom nanomaterials are expected to enhance the effect of tumor radiotherapy. Tungsten and bismuth, which contain elements with high atomic coefficients, have strong X-ray energy attenuation capability. We synthesized Bi2WO6 nanosheets (NSs) using a hydrothermal synthesis method and modified polyvinylpyrrolidone (PVP) on their surface to make them more stable. PVP-Bi2WO6 NSs have a variety of effects after absorbing X-rays (such as the photoelectric effect and Compton effect) and release a variety of particles such as photoelectrons, Compton electrons, auger electrons, and so forth, which can react with organic molecules or water in cells, generate a large number of free radicals, and promote cell apoptosis, thereby improving the effect of radiotherapy. We show through γ-H2AX and DCFH-DA probe analysis experiments that PVP-Bi2WO6 NSs can effectively increase cell DNA damage and reactive oxygen species formation under X-ray irradiation. Clone formation analysis showed that PVP-Bi2WO6 NSs can effectively suppress cell colony formation under X-ray irradiation. These versatile functions endow PVP-Bi2WO6 NSs with enhanced radiotherapy efficacy in animal models. In addition, PVP-Bi2WO6 NSs can also be used as contrast agents for X-ray computed tomography (CT) imaging with obvious effects. Therefore, PVP-Bi2WO6 NSs can be used as CT imaging contrast agents and tumor radiotherapy sensitizers and have potential medical applications.

Hydrogen sulfide exposure induces apoptosis and necroptosis through lncRNA3037/miR-15a/BCL2-A20 signaling in broiler trachea.

Hydrogen sulfide (H2S) is an air pollutant, has toxic effects on respiratory tract. However, the underlying mechanisms of H2S induced respiratory toxicity and the roles of long non-coding RNAs (lncRNA) and microRNA (miRNA) in this process remain poorly understood. To clear this, we investigated the change of tracheal tissue ultrastructure and the expression profiles of lncRNAs and miRNAs of chicken trachea exposed to H2S for 42 days. Results showed that H2S exposure triggered apoptosis, necroptosis, and differential expression of 16 lncRNAs and 18 miRNAs in broiler tracheas. The results of LMH cells stimulated by NaHS in vitro also showed the occurrence of apoptosis and necroptosis. LncRNA3037 is down-regulated and miR-15a is up-regulated in tracheal tissue and LMH cells under H2S exposure. Bioinformatics analysis and dual luciferase reporter system showed lncRNA3037 bound directly to miR-15a and negatively regulates each other. A20 and BCL2 are the target genes of miR-15a and negatively regulated by it. Overexpression of miR-15a caused apoptosis and necroptosis and its inhibition partially reversed apoptosis and necroptosis of LMH cells caused by NaHS stimulation and lncRNA3037 knockdown. Taken together, we concluded that H2S exposure mediates apoptosis and necroptosis through lncRNA3037/miR-15/A20-BCL2. These results provide new insights for unveiling the biological effects of H2S in vivo and in vitro.

TLR4-MyD88 signaling pathway is responsible for acute lung inflammation induced by reclaimed water.

Previous research found that inhalation exposure of reclaimed water could cause severe pulmonary inflammation, and the endotoxin was proposed to be the key risk factor. To further support this view, the toxic effects of different reclaimed water induced by acute inhalation exposure were compared between wildtype C57BL/6J and TLR4 signaling pathway defect mice. It was found that reclaimed water with high levels of endotoxin could induce strong inflammation in wildtype mice, but not in Tlr4-/- and MyD88-/- mutants. The mixed bacterial culture from the reclaimed water showed very weak response in wildtype mice and no response in TLR4-signaling pathway deficient mice, which further suggested that the cell-bound endotoxins contribute little in the inflammation induced by reclaimed water. In addition, conditional knockout of the Tlr4 gene in myeloid cells resulted in a significant reduction of sensitivity to the reclaimed water in mutants, which indicates that myeloid cells play the most important role in the defensive immune system against the pollutants in the water. In general, this study demonstrated that the TLR4-MyD88 signaling pathway is responsible for the acute lung inflammation induced by reclaimed water, which excludes the possibility of other signaling pathway dependent inflammation inducers in reclaimed water.

Hydrogen sulfide exposure triggers chicken trachea inflammatory injury through oxidative stress-mediated FOS/IL8 signaling.

Hydrogen sulfide (H2S) is well known to cause irritation and damage to airway following inhalation, but the mechanism by which H2S contributes to airway toxicity is unclear. In order to assess the respiratory toxicity of H2S inhalation in chicken trachea, we investigated the change of oxidative stress parameters, tracheal tissue structure and transcriptome profiles of chicken trachea exposed to H2S for 42 days. The results showed H2S exposure induced oxidative stress and inflammation in trachea. The ultrastructural analysis revealed loss of cilia and accumulation of mucus in tracheal epithelium. Differentially expressed genes (DEGs) analysis indicated 454 genes were significantly changed, including 136 genes upregulated and 318 genes downregulated. Gene ontology and KEGG analysis showed many genes involved in response to oxidative stress, inflammatory and immune response, which might contribute to H2S-induced tracheal inflammatory injury. Among those genes, N-acetyl-L-cysteine (NAC) treatment blocked the H2S-triggered expression of FOS and IL8. Silencing FOS by siRNA inhibited H2S-induced expression of IL8. Taken together, we concluded that H2S induced oxidative stress leads to tracheal inflammation through FOS/IL8 signaling, leading to excessive mucus secretion and absence of cilia. These results provide new insights for unveiling the biological effects of H2S in vivo and in vitro.

Ammonia induces Treg/Th1 imbalance with triggered NF-κB pathway leading to chicken respiratory inflammation response.

Ammonia (NH3) is a severe air pollutant and a component of haze (PM2.5). The respiratory tract is the first route of exogenous ammonia's entry into the human and animal body. Many studies have suggested that exposure to NH3 is associated with a higher risk of respiratory tract tracheitis; however, the underlying mechanism remains unclear. In this study, chicken tracheas were used as a model to investigate toxic effects and genetic changes induced by NH3 exposure, as evaluated by scanning electron microscopy (SEM) and bioinformatic analyses. The transcript analysis illustrated that NH3 exposure caused immune disorders, which play key roles in regulating inflammatory responses from NH3 exposure. Therefore, we carried out Real-time quantitative PCR (RT-PCR) and Western Blot analyses to detect the immune response genes; Treg/Th1, Th2 and Th17 secretions were found that led to inflammatory responses. Next, we also detected the NF-κB pathway and downstream genes, accompanied by cytochromes P450 (CYPs), antioxidative genes, and heat shock proteins (HSPs). Our results are consistent with transcriptome detection, indicating that ammonia has a negative effect on immune responses and causes inflammatory injury of the trachea. This study provided baseline information for exploration of the molecular mechanism of NH3-PM2.5 induced respiratory diseases.

Hydrogen sulfide exposure induces jejunum injury via CYP450s/ROS pathway in broilers.

Hydrogen sulfide (H2S) is generally recognized as a highly poisonous environmental and industrial pollutant. Previous toxicological studies of H2S are mainly focused on the nervous and cardiovascular system. There are few reports on the H2S toxicity effects on jejunum to our knowledge. Our study examined the morphological changes and antioxidant functions of broiler jejunum after the 42-day exposure to H2S. Effects of H2S on morphological damage and immune function in the broiler jejunum were analyzed from the perspective of CYP450s and oxidative stress via transcriptomics and quantitative real-time PCR (qRT-PCR). It was found that the activities of GPx, CAT, SOD, and T-AOC and the level of GSH were observably decreased (P < 0.05), while the contents of MDA and H2O2 were remarkably increased (P < 0.05) in the jejunums of broilers exposed to H2S, which undergone a process of oxidative stress, and typical inflammatory changes and apoptosis could be observed. Transcriptional profiling results showed that 208 genes were significantly up-regulated while 295 genes were remarkably down-regulated in H2S group. The expression of CYP450s, inflammation and apoptosis-related genes were also significantly increased. In conclusion, H2S led to the redox homeostasis disorder through CYP450s differential expression in broiler jejunum. The jejunal inflammatory response, apoptosis along with the immune dysfunction were subsequently observed, which eventually caused jejunal morphology and functional damage. The present study further enriches and perfects the mechanism theory of H2S toxicity on broilers, which may be valuable for the risk assessment of H2S and human health protection.

H2S inhalation-induced energy metabolism disturbance is involved in LPS mediated hepatocyte apoptosis through mitochondrial pathway.

Hydrogen sulfide (H2S) is a toxic gas and one of the air pollutants of great concern. High-concentrated H2S can induce energy metabolism disturbance and apoptosis. However, the mechanism of H2S-induced liver injuries is unknown. Lipopolysaccharide (LPS), the main component of endotoxin, can cause fulminant hepatitis. Here, we evaluated the effects of H2S combined with LPS on the energy metabolism and apoptosis pathway in the liver using a one-day-old chicken as a model. Our results showed that the expression levels of energy metabolism-related genes (AMP-activated protein kinase (AMPK), Hypoxia-inducible factor-1 (HIF-1), aconitase 2 (ACO2), hexokinase1 (HK1), hexokinase 2 (HK2), lactate dehydrogenase A (LDHA), lactate dehydrogenase B (LDHB), phosphofructokinase (PFK), pyruvate kinase (PK) and succinate dehydrogenase B (SDHB)) tended to decrease, that the status of apoptosis increased, and that the expression levels of apoptosis-related genes (caspase3, BCL2, and bax) increased in H2S group, suggesting that H2S exposure disturbed the energy metabolism in the liver and induced hepatocyte apoptosis through the mitochondrial pathway. In addition, H2S combined with the LPS aggravated the level of energy metabolism disorders and apoptosis, indicating that H2S inhalation-induced energy metabolism disturbance is involved in LPS-mediated hepatocyte apoptosis through the mitochondrial pathway.

Simulating damage onset and evolution in fully bio-resorbable composite under three-point bending.

This paper presents a strain-based damage model to predict the stress-strain relationship and investigate the damage onset and evolution of the fibre and matrix of a fully bio-resorbable phosphate glass fibre reinforced composite under three-point bending. The flexural properties of the composite are crucial, particularly when it is employed as implant for long bone fracture. In the model, the 3D case of the strain and stress was used and the response of the undamaged material was assumed to be linearly elastic. The onset of damage was indicated by two damage variables for the fibre and matrix, respectively. The damage evolution law was based on the damage variable and the facture energy of the fibre and matrix, individually. A finite element (FE) model was created to implement the constitutive model and conduct numerical tests. An auto-adaptive algorithm is integrated in the FE model to improve the convergence. The FE model was capable of predicting the flexural modulus with around 3% relative error, and the flexural strength within 2% relative error in comparison with the experimental data. The numerical indices showed that the top surface of the sample was the most vulnerable under three-point bending. It was also found that the damage initiated in the fibre, was the primary driver for composite failure under three-point bending.

Inflammatory Response Occurs in Veins of Broiler Chickens Treated with a Selenium Deficiency Diet.

Selenium (Se) has been indicated to prevent chronic diseases including cancer, cardiovascular disease, and type 2 diabetes. However, a few studies have indicated that Se deficiency can induce vascular diseases. Thus, in the present study, we investigated the effect of Se deficiency on vascular pathology. A total of 60 male broiler chickens were randomly divided into 2 groups (n = 30). The control group (C group) was fed a basic diet, and the Se-deficient group (L group) was fed a Se-deficient, corn-soy-based diet. Changes in messenger RNA (mRNA) and protein levels of inflammatory factors and inflammation-related cytokines were examined by both RT-PCR and Western blot analysis. Our results indicate that the mRNA and protein levels of inflammatory factors and inflammation-related cytokines in the L group were significantly changed in the vein. In addition, principal component analysis (PCA) was used to define the most important parameters that could be used as key factors. The in vitro experiments also demonstrated that Se can enhance the anti-inflammatory ability of vein endothelial cells. In conclusion, Se deficiency induces an inflammatory response by modulating inflammatory factors and inflammation-related cytokines.

The Impact of the Hazard Correlation between Risk Factors and Diabetes.

This study examined the occurrence of diabetes and sustainable risk factors in residents aged 30 and above of a community in Taoyuan County, Taiwan. The main purpose of this research was to explore the correlations between related variables and the occurrence of diabetes. The demographic variables, health exam variables, healthy behavior variables, and environmental variables had obvious impacts on the risk of diabetes. As age increased, the risk of developing the disease also increased; higher educational levels lowered risk, while unemployment raised it. Also, analysis of the health exam variables showed that abnormal BMIs, waist-hip ratios, and body fat percentages had significant impacts on individuals' risk of diabetes. Moreover, it was found that smoking affected the risk of having diabetes: smokers, particularly male smokers, had a relatively higher risk of developing the disease. Lastly, the results showed that exposure to second-hand smoke did not have a significant effect on the diabetes proportion in the male population. However, a significantly higher proportion of females who had been exposed to second-hand smoke had diabetes.

Cadmium induces BNIP3-dependent autophagy in chicken spleen by modulating miR-33-AMPK axis.

Cadmium (Cd), a widespread environmental pollutant, has toxic effects on organs including spleen. However, the underlying mechanisms of Cd induced spleen toxicity and the roles of micro-RNA (miRNA) in this process remain poorly understood. To investigate this, cadmium chloride (CdCl2, 10 mg/kg) was administered in the diet of chickens for 90 days. Electron microscopy, qPCR and Western blot were performed. Results showed that Cd exposure suppressed miR-33-5q which increased the levels of AMPK. Subsequently, significant decrease in AKT/mTOR signaling and HSP70 were observed. Concurrently, levels of NF-κB, p-JNK/JNK increased significantly. Moreover, the expression of BNIP3 and other autophagy markers (LC3-I, LC3-II, Beclin-1) increased significantly. Additionally, the levels of ions (Ca, Cr, Se, Sr, Sn, Ba) and (Na, Mg, V, Fe, Mo, Cu, Zn, Cd) significantly decreased and increased, respectively. Taken together, we conclude that Cd induced the deregulation of miR-33-AMPK axis led to BNIP3-dependent autophagy in chicken spleen through AKT/mTOR and HSP70-NF-κB/JNK signal pathways. In-addition Cd could affect ion homeostasis in chicken spleen.