Probabilistic human health risk assessment of PCDD/Fs near municipal solid-waste incinerator using Monte Carlo analysis coupled with triangular fuzzy numbers.

PCDD/Fs are dioxins produced by waste incineration and pose risks to human health. We aimed to detail the health risks of airborne and soil PCDD/Fs near a municipal solid-waste incinerator (MSWI) for the surrounding population and develop a new model that improves upon existing methods. Thus, we conducted field sampling and then investigated a MSWI in the Pearl River Delta (2016-2018). Our results showed that the carcinogenic and non-carcinogenic risk values of PCDD/Fs exposed to residents in nearby areas were acceptable, with hazard index (HI) values lower than 1.0 and a total carcinogenic risk lower than 1.0E-6. Notably, the results raised concerns regarding higher non-carcinogenic risks in children than in adults. Comparative analysis of the frequency accumulation diagram, accumulated probability risk, and the absolute value of error (δ) between the 95% confidence interval (CI) and the 90% CI of the Monte Carlo stochastic simulation-triangular fuzzy number (MCSS-TFN) and the MCSS model, respectively, demonstrated that the MCSS-TFN exhibited less uncertainty than the MCSS model, regardless of the health risk value of PCDD/Fs in ambient air or in soil. This observation underscores the superiority of the MCSS-TFN model over other models in assessing the health risks associated with PCDD/Fs in situations with limited data. Our new method overcomes the limited dataset size and high uncertainty in assessing the health risks of dioxin substances, providing a more comprehensive understanding of their associated health risks than MCSS models.

Intradermal vaccination with Porcilis® Begonia can clinically protect against fatal PRV challenge with the highly virulent ZJ01 field strain.

Since pseudorabies (PR) re-emerged and rapidly spread in China at the end of 2011, researchers have focused on effective vaccine strategies to prevent and control pseudorabies virus (PRV) infection in pig herds. Due to the extensive application of an attenuated vaccine based on the Bartha-K61 strain isolated in Hungary in 1961 and the variation of the PRV strain, it has been suggested that traditional vaccines based on the Bartha-K61 strain offer only partial protection against variant strains. It was therefore evaluated whether the Porcilis® Begonia vaccine, which is based on the NIA-3 strain with deletions in the gE and TK genes, is efficacious against experimental infection with the virulent, contemporary Chinese PRV strain ZJ01. In this study, piglets were vaccinated with Porcilis® Begonia through either the intradermal (ID) route or the intramuscular (IM) route and subsequently challenged intranasally with strain ZJ01 at 4 weeks post-vaccination. An unvaccinated challenge group and an unvaccinated/nonchallenged group were also included in the study. All animals were monitored for 14 days after challenge. Vaccinated and negative control pigs stayed healthy during the study, while the unvaccinated control animals developed lesions associated with PRV ZJ01 challenge, and 44% of these pigs died before the end of the experiment. This study demonstrated that ID or IM vaccination of pigs with a vaccine based on the NIA-3 strain Porcilis® Begonia clinically protects against fatal PRV challenge with the ZJ01 strain.

Health risk assessment of trace metal(loid)s in agricultural soil using an integrated model combining soil-related and plants-accumulation exposures: A case study on Hainan Island, South China.

Traditional health risk assessment of trace metal(loid)s (TMs) in agricultural soil exclusively considers direct soil-related exposure and may underestimate the health risks they pose. In this study, the health risks of TMs were evaluated using an integrated model that combined soil-related and plant-accumulating exposures. A detailed investigation of common TMs (Cr, Pb, Cd, As, and Hg) coupled with probability risk analysis based on a Monte Carlo simulation was conducted on Hainan Island. Our results showed that, except for As, the non-carcinogenic risk (HI) and carcinogenic risk (CR) of the TMs were all within the acceptable ranges (HI < 1.0, and CR < 1E-06) for direct soil-related exposure to bio-accessible fractions and indirect exposure via plant accumulation (CR substantially lower than the warning threshold 1E-04). We identified crop food ingestion as the essential pathway for TM exposure and As as the critical toxic element in terms of risk control. Moreover, we determined that RfDo and SFo are the most suitable parameters for assessing As health risk severity. Our study demonstrated that the proposed integrated model combining soil-related and plant-accumulating exposures can avoid major health risk assessment deviations. The results obtained and the integrated model proposed in this study can facilitate future multi-pathway exposure research and could be the basis for determining agricultural soil quality criteria in tropical areas.

Structural and functional biomimetics of [Fe]-hydrogenase featuring a mono-, di- or tetrasubstituted pyridine ligand with a fac-C, N, and S ligation.

The combined structural and functional modeling study of [Fe]-H2ase has remained a great challenge, to date. Now, we report a series of new structural and functional [Fe]-H2ase models (1-6) that contain a mono-, di- or tetrasubstituted pyridine ligand with a biomimetic fac-C, N, and S ligation. While models 1-3, 5 and 6 are conveniently prepared by a novel flexible pyridine ligand (FPL)-based method, model 4 is prepared simply by an intramolecular CO replacement reaction of model 3. More interestingly, the structural study by spectroscopy and X-ray crystallography proves that these new models include a biomimetic fac-acyl (or methylene) C, pyridyl N, and thioether S ligation to an Fe(II) center and the C-Fe(II) σ bond is trans to an iodo ligand. In addition, the chemical reactivity study proves that they all have the enzyme-like H2 activation and hydride transfer functions in the presence of imidazolium Im+, AgBF4 and Et3N. Particularly interesting is that a possible pathway for such H2 activation and hydride transfer reactions catalyzed by a representative model 4 is proposed and the existence of the highly unstable 5-coordinate intermediate M4 and Fe-H species M5 is supported by the isolation and characterization of their MeCN-coordinated derivative 7 and chloro-substituted derivative 8, respectively.

Biomimetic models of [Fe]-hydrogenase featuring a 2-acylphenylthiomethyl-6-R-pyridine (R = H or OMe) ligand.

Despite a variety of [Fe]-H2ase models prepared so far, the structural and functional modeling study of the enzyme has remained a great challenge. Now, we report a new type of flexible pyridine ligand (FPL)-based synthetic method by which two novel [Fe]-H2ase models have been prepared. Notably, the two models contain not only a biomimetic fac-acyl C, pyridyl N, thioether S coordination mode but also possess the enzyme-like H2/D2 activation functions.

Dynamic responses of soil enzymes at key growth stages in rice after the in situ remediation of paddy soil contaminated with cadmium and arsenic.

The practical application of in situ remediation techniques requires an understanding of the dynamic changes in soil enzyme activity as indicators of soil fertility and health. Experiments were carried out in paddy soils co-contaminated with cadmium (Cd) and arsenic (As) at low (L) and high (H) levels. A calcium and iron (CaFe)-based amendment (limestone + iron powder + silicon fertilizer + calcium­magnesium-phosphate fertilizer) was applied to the soil at concentrations of 0, 450, and 900 g·m-2 (labeled CK, T1, and T2, respectively), and sampling was conducted at the tillering (TS), booting (BS), filling (FS), and mature (MS) stages. In soil L, urease activity increased significantly by 15.8% under T1 treatment at the MS, catalase activity increased significantly under T2 treatment by 52.4% at the FS and 25.9% at the MS, and acid phosphatase activity increased significantly by 50.1%-65.9% at the TS. For soil H, urease activity increased by maximum values of 101.6% and 28.6% at the FS and MS, respectively. Catalase activity increased by 29.0% at the MS under T2 treatment, and acid phosphatase activity increased by maximum values of 40.5%, 16.0%, and 53.9% at the BS, FS, and MS, respectively. The results indicate that the changes in soil enzyme activity were mainly related to the rice growth stage, soil pH, and available Cd and As after the application of Ca-Fe-based amendment. Overall, at the FS and MS, the amendment increased the soil pH, soil enzyme activity, and cation exchange capacity and reduced the available Cd and As, which reduced the Cd and As contents in brown rice.

Prevalence and diagnostic agreement of sarcopenic obesity with different definitions among Chinese community-dwelling older adults.

OBJECTIVE: this retrospective study aims to compare the prevalence and diagnostic agreement of sarcopenic obesity (SO) using different obesity diagnostic methods among Chinese community-dwelling older adults. METHODS: SO was diagnosed with sarcopenia and obesity diagnostic methods. Sarcopenia was defined using the Asian Working Group for Sarcopenia criteria 2019 (AWGS2019). Four widely used indicators were used to define obesity: body mass index (BMI), waist circumference (WC), percent of body fat (PBF) and visceral fat area (VFA). Cohen's kappa was used to analyse the diagnosis agreement of SO between different diagnostic methods. RESULTS: a total of 1,050 participants were included, including 347 men (71.3 ± 7.4 years) and 703 women (69.9 ± 7.5 years). The prevalence of sarcopenia was 25% in total participants, there was no difference between men (24.2%) and women (25.5%), (P = 0.705). With different obesity diagnostic methods, the obesity prevalence ranged from 4.1 to 42.2%, the SO prevalence was 0.1-7.9%. The diagnosis agreement of SO was poor-to-moderate (κ ranged from -0.002 to 0.682). Among the four diagnostic methods, AWGS combined with BMI had the poorest agreement (κ = -0.002 with other methods), AWGS combined with VFA had the best agreement (κ = 0.641 and 0.682 with AWGS combined with PBF and with AWGS combined with WC, respectively). CONCLUSION: the prevalence of SO vary considerably and the diagnostic agreement is poor-to-moderate with non-uniform diagnostic methods. BMI has the lowest sensitivity, whereas VFA has the highest sensitivity in diagnosis of SO, and VFA has a relatively good diagnostic agreement with other diagnostic methods.

Development and Validation of a Nomogram for Predicting Sarcopenia in Community-Dwelling Older Adults.

OBJECTIVE: To establish and validate a nomogram that predicts the risk of sarcopenia for community-dwelling older residents. DESIGN: Retrospective study. SETTING AND PARTICIPANTS: A total of 1050 community-dwelling older adults. METHODS: Data from a survey of community-dwelling older residents (≥60 years old) in Hunan, China, from June to September 2019 were retrospectively analyzed. The survey included general demographic information, diet, and exercise habits. Sarcopenia diagnosis was according to 2019 Asian Working Group for Sarcopenia criteria. Participants were randomly divided into the development group and validation groups. Independent risk factors were screened by multivariate logistic regression analysis. Based on the independent risk factors, a nomogram model was developed to predict the risk of sarcopenia for community-dwelling older adults. Both in the development and validation sets, the discrimination, calibration, and clinical practicability of the nomogram were verified using receiver operating characteristic curve analysis, Hosmer-Lemeshow test, and decision curve analysis, respectively. RESULTS: Sarcopenia was identified in 263 (25.0%) participants. Age, body mass index, marital status, regular physical activity habit, uninterrupted sedentary time, and dietary diversity score were significant contributors to sarcopenia risk. A nomogram for predicting sarcopenia in community-dwelling older adults was developed using these factors. Receiver operating characteristic curve analysis showed that the area under the curve was 0.827 (95% CI 0.792-0.860) and 0.755 (95% CI 0.680-0.837) in the development and validation sets, respectively. The Hosmer-Lemeshow test yielded P values of .609 and .565, respectively, for the 2 sets. The nomogram demonstrated a high net benefit in the clinical decision curve in both sets. CONCLUSIONS AND IMPLICATIONS: This study developed and validated a risk prediction nomogram for sarcopenia among community-dwelling older adults. Sarcopenia risk was classified as low (<11%), moderate (11%-70%), and high (>70%). This nomogram provides an accurate visual tool to medical staff, caregivers, and older adults for prediction, early intervention, and graded management of sarcopenia.

Brown Adipose Tissue Activation Is Involved in Atherosclerosis of ApoE-/- Mice Induced by Chronic Intermittent Hypoxia.

Background: Obstructive sleep apnea is an atherogenesis factor of which chronic intermittent hypoxia is a prominent feature. Chronic intermittent hypoxia (CIH) exposure can sufficiently activate the sympathetic system, which acts on the ß3 adrenergic receptors of brown adipose tissue (BAT). However, the activity of BAT and its function in CIH-induced atherosclerosis have not been fully elucidated. Methods: This study involved ApoE-/- mice which were fed with a high-fat diet for 12 weeks and grouped into control and CIH group. During the last 8 weeks, mice in the CIH group were housed in cages to deliver CIH (12 h per day, cyclic inspiratory oxygen fraction 5-20.9%, 180 s cycle). Atherosclerotic plaques were evaluated by Oil Red O, hematoxylin and eosin, Masson staining, and immunohistochemistry. Afterward, we conducted immunohistochemistry, western blotting, and qRT-PCR of uncoupling protein 1 (UCP1) to investigate the activation of BAT. The level of serum total cholesterol (TC), triglyceride, low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), and free fatty acid (FFA) were measured. Finally, RNA-Sequencing was deployed to explore the differentially expressed genes (DEGs) and their enriched pathways between control and CIH groups. Results: Chronic intermittent hypoxia exposure promoted atherosclerotic plaque area with increasing CD68, α-SMA, and collagen in plaques. BAT activation was presented during CIH exposure with UCP1 up-regulated. Serum TC, triglyceride, LDL-c, and FFA were increased accompanied by BAT activation. HDL-c was decreased. Mechanistically, 43 lipolysis and lipid metabolism-associated mRNA showed different expression profiling between the groups. Calcium, MAPK, and adrenergic signaling pathway included the most gene number among the significantly enriched pathways. Conclusion: This study first demonstrated that BAT activation is involved in the progression of CIH-induced atherosclerosis, possibly by stimulating lipolysis.

Fe-S Catalyst Generated In Situ from Fe(III)- and S3•--Promoted Aerobic Oxidation of Terminal Alkenes.

An iron-sulfur complex formed by the simple mixture of FeCl3 with S3•- generated in situ from K2S is developed and applied to selective aerobic oxidation of terminal alkenes. The reaction was carried out under an atmosphere of O2 (balloon) and could proceed on a gram scale, expanding the application of S3•- in organic synthesis. This study also encourages us to explore the application of an Fe-S catalyst in organic reactions.

Early combined rehabilitation intervention to improve the short-term prognosis of premature infants.

BACKGROUND: To explore the clinical effect of early combined rehabilitation intervention on premature infants in the neonatal intensive care unit (NICU). METHODS: Premature infants with gestational ages less than 32 weeks or birth weights less than 1500 g were included in the present study.The participants were divided into the intervention group and control group. All infants received the current routine treatment based on the clinical guidelines, and the intervention group was additionally treated by visual and auditory stimulation, oral motor function, respiratory function and neurodevelopmental training. The following clinical outcomes were compared: durations of oxygen supplementation and indwelling gastric tube use; incidences of retinopathy of prematurity (ROP) and neonatal necrotizing enterocolitis (NEC); Sliverman scores; incidences of bronchopulmonary dysplasia (BPD) and intraventricular haemorrhage; days of hospitalization; and neurodevelopmental outcomes. Datas were analysed using the following statistical tests: the chi-square test, the independent samples or paired t test, repeated measures ANOVA, and the Wilcoxon rank sum test. RESULTS: Compared with those in the control group, premature infants in the intervention group had shorter durations of oxygen supplementation and indwelling gastric tube use, fewer hospitalization days and lower incidences of ROP, BPD, and NEC.The intervention group had lower Sliverman scores and higher Ballard neuromuscular scores than the control group. CONCLUSION: Early combined rehabilitation intervention can improve the short-term clinical outcomes of premature infants.

New insights into BMP9 signaling in liver diseases.

Bone morphogenetic protein 9 (BMP9) is a recently discovered cytokine mainly secreted by the liver and is a member of the transforming growth factor ß (TGF-ß) superfamily. In recent years, an increasing number of studies have shown that BMP9 is associated with liver diseases, including nonalcoholic fatty liver disease (NAFLD), liver fibrosis and hepatocellular carcinoma (HCC), and BMP9 signaling may play dual roles in liver diseases. In this review, we mainly summarized and discussed the roles and potential mechanisms of BMP9 signaling in NAFLD, liver fibrosis and HCC. Specifically, this article will provide a better understanding of BMP9 signaling and new clues for the treatment of liver diseases.

Centromere protein U enhances the progression of bladder cancer by promoting mitochondrial ribosomal protein s28 expression.

Bladder cancer is one of the most common types of cancer. Most gene mutations related to bladder cancer are dominantly acquired gene mutations and are not inherited. Previous comparative transcriptome analysis of urinary bladder cancer and control samples has revealed a set of genes that may play a role in tumor progression. Here we set out to investigate further the expression of two candidate genes, centromere protein U (CENPU) and mitochondrial ribosomal protein s28 (MRPS28) to better understand their role in bladder cancer pathogenesis. Our results confirmed that CENPU is up-regulated in human bladder cancer tissues at mRNA and protein levels. Gain-of-function and loss-of-function studies in T24 human urinary bladder cancer cell line revealed a hierarchical relationship between CENPU and MRPS28 in the regulation of cell viability, migration and invasion activity. CENPU expression was also up-regulated in in vivo nude mice xenograft model of bladder cancer and mice overexpressing CENPU had significantly higher tumor volume. In summary, our findings identify CENPU and MRPS28 in the molecular pathogenesis of bladder cancer and suggest that CENPU enhances the progression of bladder cancer by promoting MRPS28 expression.

Comparison of Three Screening Methods for Sarcopenia in Community-Dwelling Older Persons.

OBJECTIVE: The 2019 Asian Working Group on Sarcopenia in Older People (AWGS 2019) recommends using either calf circumference or the strength, assistance in walking, rising from a chair, climbing stairs, and falls (SARC-F) or SARC-F combined with calf circumference (SARC-CalF) questionnaires for sarcopenia screening. The aim of this study was to compare the ability and applicability of calf circumference, SARC-F, and SARC-CalF for screening sarcopenia among community-dwelling older adults. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: A total of 1050 community-dwelling older people were enrolled. METHODS: Sarcopenia was diagnosed according to the AWGS 2019 criteria: bioimpedance analysis for appendicular skeletal muscle index, hand grip, and 6-m gait speed test. Participants also completed the SARC-F questionnaire and calf circumference measurement. The screening tools' performances were evaluated through receiver operating characteristic (ROC) curves, area under the ROC curves (AUC), and sensitivity/specificity analyses. RESULTS: Sarcopenia was identified in 263 (25.0%) participants by the AWGS 2019 criteria. Calf circumference had a sensitivity of 81.4% and a specificity of 77.0%. Sensitivity and specificity of SARC-F for screening sarcopenia were 17.9% and 93.7%, respectively. SARC-CalF improved the sensitivity of SARC-F (47.5%) while keeping similar specificity (92.0%). The AUCs of calf circumference, SARC-F, and SARC-CalF were 0.79 [95% confidence interval (CI), 0.77-0.82], 0.56 (95% CI, 0.52-0.59), and 0.70 (95% CI, 0.67-0.73), respectively. The differences across ROC curves were statistically significant among 3 screening tools (P < .001). CONCLUSIONS AND IMPLICATIONS: The overall screening ability of calf circumference was better than that of SARC-F and SARC-CalF for sarcopenia in community-dwelling older persons despite gender, age, and cognitive function. SARC-F and SARC-CalF have high specificity but are susceptible to the preceding factors.

Pharyngeal Ectopic Thymus: A Case Report.

Pharyngeal ectopic thymus is a rare cause of pharyngeal masses and is rarely considered in the differential diagnosis of neck and head masses in children. In this paper, the case of an infant with a pharyngeal ectopic thymus is presented and our intraoral surgical approach in the patient's treatment is described.

Oleic Acid (OA), A Potential Dual Contrast Agent for Postmortem MR Angiography (PMMRA): A Pilot Study.

Choosing proper perfusates as contrast agents is an important aspect for postmortem magnetic resonance angiography (PMMRA). However, in this emerging field, the number of suitable kinds of liquid is still very limited. The objective of this research is to compare MR images of oleic acid (OA) with paraffin oil (PO) in vitro and in ex situ animal hearts, in order to evaluate the feasibility to use OA as a novel contrast agent for PMMRA. In vitro, OA, PO and water (control) were introduced into three tubes separately and T1weighted-spin echo (T1w-SE) and T2w-SE images were acquired on a 1.5T MR scanner. In the second experiment, OA and PO were injected into left coronary artery (LCA) and left ventricle (LV) of ex situ bovine hearts and their T1w-SE, T2w-SE, T1w-multipoint Dixon (T1w-mDixon) and 3DT2w-mDixon images were acquired. The overall results indicate that OA may have a potential to be used as a dual (T1 and T2 based) contrast agent for PMMRA when proper sequence parameters are utilized. However, as the pilot study was based on limited number of animal hearts, more researches using OA in cadavers are needed to validate our findings.

[Aerobic exercise reduces the expression of pyroptosis-related proteins and inflammatory factors in hippocampus of mice with insulin resistance].

The aim of the present study was to observe the expression of pyroptosis- and inflammation-related proteins in the hippocampus of mice with insulin resistance (IR) after aerobic exercise, and to explore the possible mechanism of exercise to improve IR. C57BL/6J male mice of 6 weeks old were randomly fed with normal diet (n = 12) and high-fat diet (HFD) (n = 26) for 12 weeks respectively. Glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed to determine whether IR occurred in HFD mice. Then the mice were randomly divided into control group (n = 12), IR group (n = 10) and IR + aerobic exercise group (AE, n = 10). Mice in AE group performed a 12-week progressive speed treadmill training after being adapted to the treadmill for one week. After the intervention, the expression of pyroptosis- and inflammation-related proteins in hippocampus was detected by Western blot. The results showed that compared with control group, NFκB, Nod-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing CARD (ASC), pyroptosis-related proteins like pro-Caspase-1, gasdermin D (GSDMD), GSDMD-N, and inflammatory factors IL-1ß, IL-18 were significantly increased. The inflammasome-related protein NIMA-related kinase 7 (NEK7) and pyroptosis-related protein Caspase-1 showed an increasing trend, but there was no significant difference. Compared with the IR group, progressive speed treadmill training significantly reduced the expression of NFκB, NLRP3, NEK7, ASC, pro-Caspase-1, GSDMD, GSDMD-N, IL-1ß, and IL-18 in the hippocampus of mice with IR. These results suggested 12-week progressive speed treadmill training can significantly reduce the expression of pyroptosis-related proteins and inflammatory factors in the hippocampus of mice with IR, and inhibit pyroptosis.

Folium Sennae and emodin reverse airway smooth muscle contraction.

The objective of this project was to find a bronchodilatory compound from herbs and clarify the mechanism. We found that the ethanol extract of Folium Sennae (EEFS) can relax airway smooth muscle (ASM). EEFS inhibited ASM contraction, induced by acetylcholine, in mouse tracheal rings and lung slices. High-performance liquid chromatography assay showed that EEFS contained emodin. Emodin had a similar reversal action. Acetylcholine-evoked contraction was also partially reduced by nifedipine (a selective inhibitor of L-type voltage-dependent Ca2+ channels, LVDCCs), YM-58483 (a selective inhibitor of store-operated Ca2+ entry, SOCE), as well as Y-27632 (an inhibitor of Rho-associated protein kinase). In addition, LVDCC- and SOCE-mediated currents and cytosolic Ca2+ elevations were inhibited by emodin. Emodin reversed acetylcholine-caused increases in phosphorylation of myosin phosphatase target subunit 1. Furthermore, emodin, in vivo, inhibited acetylcholine-induced respiratory system resistance in mice. These results indicate that EEFS-induced relaxation results from emodin inhibiting LVDCC, SOCE, and Ca2+ sensitization. These findings suggest that Folium Sennae and emodin may be new sources of bronchodilators.

Author Correction: Increased circulating ß2-adrenergic receptor autoantibodies are associated with smoking-related emphysema.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The Molecular Mechanisms of Excessive Hippocampal Endoplasmic Reticulum Stress Depressing Cognition-related Proteins Expression and the Regulatory Effects of Nrf2.

Studies have shown that obesity-induced hyperglycemia and hyperlipidemia could cause increased hippocampal endoplasmic reticulum (ER) stress and impaired cognition-related proteins expression, resulting in learning and memory impairment. Meanwhile, aerobic exercise could activate hippocampal nuclear factor erythroid 2-related factor 2 (Nrf2) reducing ER stress. This study investigated the underlying molecular mechanisms of this effect. In order to clarify the relationship among ER stress, Nrf2 signaling and cognition-related proteins expression in vitro, we respectively treated hippocampal cells with high glucose and palmitic acid (PA), ER stress inhibitor 4-phenylbutyrate (4-PBA), and Nrf2 activator Tert-Butylhydroquinone (TBHQ). Results showed that the expression levels of glucose transporter 3 (GLUT3), fatty acid transport protein 1 (FATP1), ER stress biomarkers (GRP78, p-PERK, p-IRE1α and p-eIF2α), ER stress-mediated apoptosis biomarkers (caspase-12, CHOP and Bax/Bcl-2), and the activity of NLRP3-IL-1ß inflammatory pathway were significantly increased under high glucose and PA conditions, accompanied with depressed p38/ERK-CREB pathway and decreased levels of brain derived neurotrophic factor (BDNF) and synaptophysin (SYN). On the other hand, both 4-PBA and TBHQ reduced ER stress and reversed the expression of the above-mentioned proteins. Our findings suggest that high glucose and PA could induce excessive ER stress and apoptosis via promoting the overexpression of GLUT3 and FATP1, and ER stress could suppress BDNF and SYN expression through negatively regulating p38/ERK-CREB pathway and positively regulating NLRP3-IL-1ß pathway, which could be reversed by activated Nrf2-HO-1 pathway.