The role of BTG2/PI3K/AKT pathway-mediated microglial activation in T-2 toxin-induced neurotoxicity.

T-2 toxin is one of the mycotoxins widely distributed in human food and animal feed. Our recent work has shown that microglial activation may contribute to T-2 toxin-induced neurotoxicity. However, the molecular mechanisms involved need to be further clarified. To address this, we employed high-throughput transcriptome sequencing and found altered B cell translocation gene 2 (BTG2) expression levels in microglia following T-2 toxin treatment. It has been shown that altered BTG2 expression is involved in a range of neurological pathologies, but whether it's involved in the regulation of microglial activation is unclear. The aim of this study was to investigate the role of BTG2 in T-2 toxin-induced microglial activation. The results of animal experiments showed that T-2 toxin caused neurobehavioral disorders and promoted the expression of microglial BTG2 and pro-inflammatory activation of microglia in hippocampus and cortical, while microglial inhibitor minocycline inhibited these changes. The results of in vitro experiments showed that T-2 toxin enhanced BTG2 expression and pro-inflammatory microglial activation, and inhibited BTG2 expression weakened T-2 toxin-induced microglial activation. Moreover, T-2 toxin activated PI3K/AKT and its downstream NF-κB signaling pathway, which could be reversed after knock-down of BTG2 expression. Meanwhile, the PI3K inhibitor LY294002 also blocked this process. Therefore, BTG2 may be involved in T-2 toxin's ability to cause microglial activation through PI3K/AKT/NF-κB pathway.

Ultrasensitive Self-Powered Flexible Crystalline ß-Ga2O3-Based Photodetector Obtained through Lattice Symmetry and Band Alignment Engineering.

Due to its portable and self-powered characteristics, the construction of Ga2O3-based semiconductor flexible devices that can improve the adaptability in various complex environments have drawn great attention in recent decades. However, conventional Ga2O3-based flexible heterojunctions are based on either amorphous or poor crystalline Ga2O3 materials, which severely limit the performance of the corresponding devices. Here, through lattice-symmetry and energy-band alignment engineering, we construct a high-quality crystalline flexible NiO/ß-Ga2O3 p-n self-powered photodetector. Owing to its suitable energy-band alignment structure, the device shows a high photo-to-dark current ratio (1.71 × 105) and a large detection sensitivity (6.36 × 1014 Jones) under zero bias, which is superior than most Ga2O3 self-powered photodetectors even for those based on rigid substrates. Moreover, the fabricated photodetectors further show excellent mechanical stability and robustness in bending conditions, demonstrating their potential practical applications in flexible optoelectronic devices. These findings provide insights into the manipulation of crystal lattice and energy band engineering in flexible self-powered photodetectors and also offer guideline for designing other Ga2O3-based flexible electronic devices.

High ambient temperature may increase the risk of anemia in pregnancy: Identifying susceptible exposure windows.

Anemia in pregnancy (AIP) is associated with multiple severe maternal and perinatal adverse outcomes. However, there is a lack of evidence on the association between environmental factors and AIP. Aim to explore the association between ambient temperature and the risk of AIP, and identify susceptible exposure windows, we conducted a matched case-control study from 2013 to 2016 in Xi'an, China, which included 710 women with AIP and 1420 women without AIP. The conditional logistic regression model was used to evaluate the association between ambient temperature and AIP at different gestational weeks and gestational months. The association between extreme temperature and AIP was evaluated using the distributed lag nonlinear model (DLNM). We conducted stratified analyses of age, parity, and season of conception, and estimated the interaction between ambient temperature and air pollutants on AIP. Ambient temperature was significantly positively associated with the risk of AIP, and the susceptible exposure windows were 2-25 gestational weeks and 1-6 gestational months, respectively. The strongest effect was observed in the week 8 and month 2, for each 1 °C increase in weekly and monthly mean temperature, the odds ratio (OR) for AIP was 1.038 (95 % confidence interval (CI): 1.022, 1.055) and 1.040 (95 % CI: 1.020, 1.060), respectively. Extreme heat may increase the risk of AIP. Stratified analyses showed that there was no significant difference among different age, parity, and season of conception groups. No significant interaction effect of ambient temperature with air pollution on AIP was found. In summary, high ambient temperature may increase the risk of AIP, and the first and second trimesters may be susceptible exposure windows. Understanding the effect of temperature on pregnant women will be beneficial to reduce the occurrence of AIP.

Antisense oligonucleotide targeting hepatic Serum Amyloid A limits the progression of angiotensin II-induced abdominal aortic aneurysm formation.

BACKGROUND AND AIMS: Obesity increases the risk for abdominal aortic aneurysms (AAA) in humans and enhances angiotensin II (AngII)-induced AAA formation in C57BL/6 mice. We reported that deficiency of Serum Amyloid A (SAA) significantly reduces AngII-induced inflammation and AAA in both hyperlipidemic apoE-deficient and obese C57BL/6 mice. The aim of this study is to investigate whether SAA plays a role in the progression of early AAA in obese C57BL/6 mice. METHODS: Male C57BL/6J mice were fed a high-fat diet (60% kcal as fat) throughout the study. After 4 months of diet, the mice were infused with AngII until the end of the study. Mice with at least a 25% increase in the luminal diameter of the abdominal aorta after 4 weeks of AngII infusion were stratified into 2 groups. The first group received a control antisense oligonucleotide (Ctr ASO), and the second group received ASO that suppresses SAA (SAA-ASO) until the end of the study. RESULTS: Plasma SAA levels were significantly reduced by the SAA ASO treatment. While mice that received the control ASO had continued aortic dilation throughout the AngII infusion periods, the mice that received SAA-ASO had a significant reduction in the progression of aortic dilation, which was associated with significant reductions in matrix metalloprotease activities, decreased macrophage infiltration and decreased elastin breaks in the abdominal aortas. CONCLUSIONS: We demonstrate for the first time that suppression of SAA protects obese C57BL/6 mice from the progression of AngII-induced AAA. Suppression of SAA may be a therapeutic approach to limit AAA progression.

Freestanding Crystalline ß-Ga2O3 Flexible Membrane Obtained via Lattice Epitaxy Engineering for High-Performance Optoelectronic Device.

Wearable and flexible ß-Ga2O3-based semiconductor devices have attracted considerable attention, due to their outstanding performance and potential application in real-time optoelectronic monitoring and sensing. However, the unavailability of high-quality crystalline and flexible ß-Ga2O3 membranes limits the fabrication of relevant devices. Here, through lattice epitaxy engineering together with the freestanding method, we demonstrate the preparation of a robust bending-resistant and crystalline ß-Ga2O3 (-201) membrane. Based on this, we fabricate a flexible ß-Ga2O3 photodetector device that shows comparable performance in photocurrent responsivity and spectral selectivity to conventional rigid ß-Ga2O3 film-based devices. Moreover, based on the transferred ß-Ga2O3 membrane on a silicon wafer, the PEDOT:PSS/ß-Ga2O3 p-n heterojunction device with self-powered characteristic was constructed, further demonstrating its superior heterogeneous integration ability with other functional materials. Our results not only demonstrate the feasibility of obtaining a high-quality crystalline and flexible ß-Ga2O3 membrane for an integrated device but also provide a pathway to realize flexible optical and electronic applications for other semiconducting materials.

Deficiency of Acute-Phase Serum Amyloid A Exacerbates Sepsis-Induced Mortality and Lung Injury in Mice.

Serum amyloid A (SAA) is a family of proteins, the plasma levels of which may increase >1000-fold in acute inflammatory states. We investigated the role of SAA in sepsis using mice deficient in all three acute-phase SAA isoforms (SAA-TKO). SAA deficiency significantly increased mortality rates in the three experimental sepsis mouse models: cecal ligation and puncture (CLP), cecal slurry (CS) injection, and lipopolysaccharide (LPS) treatments. SAA-TKO mice had exacerbated lung pathology compared to wild-type (WT) mice after CLP. A bulk RNA sequencing performed on lung tissues excised 24 h after CLP indicated significant enrichment in the expression of genes associated with chemokine production, chemokine and cytokine-mediated signaling, neutrophil chemotaxis, and neutrophil migration in SAA-TKO compared to WT mice. Consistently, myeloperoxidase activity and neutrophil counts were significantly increased in the lungs of septic SAA-TKO mice compared to WT mice. The in vitro treatment of HL-60, neutrophil-like cells, with SAA or SAA bound to a high-density lipoprotein (SAA-HDL), significantly decreased cellular transmigration through laminin-coated membranes compared to untreated cells. Thus, SAA potentially prevents neutrophil transmigration into injured lungs, thus reducing exacerbated tissue injury and mortality. In conclusion, we demonstrate for the first time that endogenous SAA plays a protective role in sepsis, including ameliorating lung injury.

Mutant p53 and ELK1 co-drive FRA-1 expression to induce metastasis in breast cancer.

Tumor-associated p53 mutations induce activities different from wild-type p53, thus causing loss of the protein's tumor inhibition function. The cells carrying p53 mutations have more aggressive characteristics related to invasion, metastasis, proliferation, and cell survival. By comparing the gene expression profiles of mutant p53 (mutp53) and mutp53 silenced cohorts, we found that FOS-related antigen-1 (FRA-1), which is encoded by FOSL1, is a potential effector of mutp53-mediated metastasis. We demonstrate that the expression of FRA-1, a gatekeeper of mesenchymal-epithelial transition, is elevated in the presence of p53 mutations. Mechanistically, mutant p53 cooperates with the transcription factor ELK1 in binding and activating the promoter of FOSL1, thus fostering lung metastasis. This study reveals new insights into how mutant p53 contributes to metastasis in breast cancer.

Antisense Oligonucleotide Targeting Hepatic Serum Amyloid A Limits the Progression of Angiotensin II-Induced Abdominal Aortic Aneurysm Formation.

OBJECTIVE: Obesity increases the risk for abdominal aortic aneurysms (AAA) in humans and enhances angiotensin II (AngII)-induced AAA formation in C57BL/6 mice. Obesity is also associated with increases in serum amyloid A (SAA). We previously reported that deficiency of SAA significantly reduces AngII-induced inflammation and AAA in both hyperlipidemic apoE-deficient and obese C57BL/6 mice. In this study, we investigated whether SAA plays a role in the progression of early AAA in obese C57BL/6 mice. APPROACH AND RESULTS: Male C57BL/6J mice were fed a high-fat diet (60% kcal as fat) throughout the study. After 4 months of diet, the mice were infused with angiotensin II (AngII) until the end of the study. Mice with at least a 25% increase in the luminal diameter of the abdominal aorta after 4 weeks of AngII infusion were stratified into 2 groups. The first group received a control antisense oligonucleotide (Ctr ASO), and the second group received ASO that suppresses SAA (SAA-ASO) until the end of the study. Plasma SAA levels were significantly reduced by the SAA ASO treatment. While mice that received the control ASO had continued aortic dilation throughout the AngII infusion periods, the mice that received SAA-ASO had a significant reduction in the progression of aortic dilation, which was associated with significant reductions in matrix metalloprotease activities, decreased macrophage infiltration and decreased elastin breaks in the abdominal aortas. CONCLUSION: We demonstrate for the first time that suppression of SAA protects obese C57BL/6 mice from the progression of AngII-induced AAA. Suppression of SAA may be a therapeutic approach to limit AAA progression.

Serum amyloid A augments the atherogenic effects of cholesteryl ester transfer protein.

Serum amyloid A (SAA) is predictive of CVD in humans and causes atherosclerosis in mice. SAA has many proatherogenic effects in vitro. However, HDL, the major carrier of SAA in the circulation, masks these effects. The remodeling of HDL by cholesteryl ester transfer protein (CETP) liberates SAA restoring its proinflammatory activity. Here, we investigated whether deficiency of SAA suppresses the previously described proatherogenic effect of CETP. ApoE-/- mice and apoE-/- mice deficient in the three acute-phase isoforms of SAA (SAA1.1, SAA2.1, and SAA3; "apoE-/- SAA-TKO") with and without adeno-associated virus-mediated expression of CETP were studied. There was no effect of CETP expression or SAA genotype on plasma lipids or inflammatory markers. Atherosclerotic lesion area in the aortic arch of apoE-/- mice was 5.9 ± 1.2%; CETP expression significantly increased atherosclerosis in apoE-/- mice (13.1 ± 2.2%). However, atherosclerotic lesion area in the aortic arch of apoE-/- SAA-TKO mice (5.1 ± 1.1%) was not significantly increased by CETP expression (6.2 ± 0.9%). The increased atherosclerosis in apoE-/- mice expressing CETP was associated with markedly increased SAA immunostaining in aortic root sections. Thus, SAA augments the atherogenic effects of CETP, which suggests that inhibiting CETP may be of particular benefit in patients with high SAA.

Unveiling Strong Ion-Electron-Lattice Coupling and Electronic Antidoping in Hydrogenated Perovskite Nickelate.

Despite being highly promising for applications in emergent electronic devices, decoding both the ion-electron-lattice coupling in correlated materials at the atomic scale and the electronic band structure remains a big challenge due to the strong and complex correlation among these degrees of freedom. Here, taking an epitaxial thin film of perovskite nickelate NdNiO3 as a model system, hydrogen-ion-induced giant lattice distortion and enhanced NiO6 octahedra tilting/rotation are demonstrated, which leads to a new robust hydrogenated HNdNiO3 phase with lattice expansion larger than 10% on a series of substrates. Moreover, under the effect of ion-electron synergistic doping, it is found that the proposed electronic antidoping, i.e., the doped electrons mainly fill the ground-state oxygen 2p holes instead of changing the Ni oxidation state from Ni3+ to Ni2+ , dominates the metal-insulator transition. Meanwhile, lattice modification with enhanced Ni-O-Ni bond tilting or rotation mainly modifies the orbital density of states near the Fermi level. Last, by electric-field-controlled hydrogen-ion intercalation and its strong coupling to the lattice and electron charge, selective micrometer-scale patterns with distinct structural and electronic states are fabricated. The results provide direct evidence for a strong ion-electron-lattice coupling in correlated physics and exhibit its potential applications in designing novel materials and devices.

Unexpected association between ambient ozone and adult insomnia outpatient visits: A large-scale hospital-based study.

Growing evidence indicates that short-term ozone (O3) exposure has substantial health consequences, but the relationship between short-term ambient O3 and insomnia, a common sleep disorder, is not clear. This study aimed to investigate the short-term effects of ambient O3 exposure on outpatient visits for adult insomnia and to explore the potential modifiers. A large-scale multihospital-based study was carried out in Chongqing, the largest city in Southwest China. Daily data on outpatient visits for adult insomnia, average concentrations of ambient air pollutants and meteorological factors were collected. We conducted quasi-Poisson regression with generalized additive model to assess the association between ambient O3 and outpatient visits for adult insomnia in varied windows of exposure. Subgroup analyses were applied to identify its modifiers. Totally, 140,159 adult insomnia outpatient visits were identified. The daily maximum 8-h average concentration of O3 was 69 µg/m3 during the study period, which greatly below the updated Chinese and WHO recommended limits (daily maximum 8-h average, O3: 100 µg/m3). Short-term O3 exposure was significantly negatively associated with outpatient visits for adult insomnia in different lag periods and the greatest decrease of outpatient visits for adult insomnia was found at lag 02 [0.93% (95% CI: 0.48%, 1.38%)]. Additionally, stronger links between O3 and adult insomnia outpatient visits were presented in cool seasons, and we did not observe any significant modified effects of gender and age. Moreover, the negative O3-insomnia association remained robust after controlling for other common air pollutants and comorbidities. In summary, short-term exposure to lower level of ambient O3, was associated with reduced daily outpatient visits for adult insomnia and such association showed to be more obvious in cool seasons.

The role of extreme high humidex in depression in chongqing, China: A time series-analysis.

As global climate change intensifies, people are paying increasing attention to the impact of temperature changes on adverse mental health outcomes, especially depression. While increasing attention has been paid to the effect of temperature, there is little research on the effect of humidity. We aimed to investigate the association between humidex, an index combining temperature and humidity to reflect perceived temperature, and outpatient visits for depression from 2014 to 2019 in Chongqing, the largest and one of the most hot and humid cities of China. We also aimed to further identify susceptible subgroups. A distributed lag non-linear model (DLNM) was used to explore the concentration-response relationship between humidex and depression outpatient visits. Hierarchical analysis was carried out by age and gender. A total of 155,436 visits for depression were collected from 2014 to 2019 (2191 days). We found that depression outpatient visits were significantly associated with extremely high humidex (≥40). The significant positive single-lag day effect existed at lag 0 (RR = 1.029, 95%CI: 1.000-1.059) to lag 2 (RR = 1.01, 95%CI: 1.004-1.028), and lag 12 (RR = 1.013, 95%CI: 1.002-1.024). The significant cumulative adverse effects lasted from lag 01 to lag 014. Hierarchical analyses showed that females and the elderly (≥60 years) appeared to be more susceptible to extremely high humidex. The attributable numbers (AN) and fraction (AF) of extremely high humidex on depression outpatients were 1709 and 1.10%, respectively. Extremely high humidex can potentially increase the risk of depression, especially in females and the elderly. More protective measures should be taken in vulnerable populations.

Association between maternal short-term exposure to ambient air pollution and the risk of fetal distress: A matched case-control study.

BACKGROUND: Ambient air pollution has been linked to gestational complications. However, the evidence on the relationship between air pollution and fetal distress is limited. OBJECTIVES: To investigate the relationship between maternal short-term air pollution exposure and fetal distress, and to identify a potential susceptible population. METHODS: This matched case-control study, involving 313 pregnancy women with fetal distress was conducted in Xi'an, the largest city in Northwest China from 2013 to 2016. Each woman with fetal distress was randomly matched with four women without fetal distress of the same age, same gestational week, and registration in the same period (n = 1252). Inverse distance-weighted (IDW) interpolation was applied to estimate maternal air pollution exposure based on the residential addresses. We employed conditional logistic regression model to evaluate the relationship between air pollutants and fetal distress. Distributed lag nonlinear model (DLNM) was performed to examine the exposure-response relationship between air pollutants and fetal distress. RESULTS: Maternal short-term exposure to PM10, PM2.5-10 (PMc), SO2, NO2, and CO was associated with increased risk of fetal distress. Each 10 µg/m3 increment in PM10, PMc, SO2 at lag 014, and NO2 at lag 010, the odds ratio (ORs) of fetal distress were 1.027 (95 % confidence interval (CI): 1.004, 1.050), 1.058 (95 % CI: 1.014, 1.105), 1.140 (95 % CI: 1.029, 1.264), and 1.158 (95 % CI: 1.046, 1.283), respectively. Similarly, with a 0.1 mg/m3 increment in CO at lag 014, the OR of fetal distress was 1.029 (95 % CI: 1.002, 1.058). Stratified analyses showed that the estimate associations of PM10, PM2.5 and CO appeared to be stronger, although not statistically significantly, among women with gestational complications. CONCLUSION: Maternal short-term exposure to ambient air pollution may increase the risk of fetal distress. Understanding the detrimental role of air pollution in fetal distress can help us better develop preventative methods in reducing its' impact on maternal and fetal health.

Association between ambient carbon monoxide levels and hospitalization costs of patients with myocardial infarction: Potential effect modification by ABO blood group.

Previous researches have reported the association between air pollution and various diseases. However, few researches have investigated whether air pollutants are associated with the economic loss resulting from patients' hospitalization, especially the economic loss of hospitalization due to acute cardiovascular events. The purpose of our research was to explore the association between the levels of carbon monoxide (CO), taken as an index of pollution, and the hospitalization costs of myocardial infarction (MI), and the potential effect modification by the ABO blood group. A total of 3237 MI inpatients were included in this study. A multiple linear regression model was used to evaluate the association between ambient CO levels and hospitalization costs of MI patients. Moreover, we performed stratified analyses by age, gender, body mass index (BMI), season, hypertension, and ABO blood types. There was a positive association between the levels of CO in the air and the costs of hospitalization caused by MI. Furthermore, such association was stronger in males, BMI ≥25, <65 years, with hypertension, and non-O blood group. Interestingly, we found the association was particularly significant in patients with blood group B. Overall, our study first found that ambient CO levels could have an impact on the hospitalization costs for MI patients, and those with blood group B can be more sensitive.

The association between short-term ambient sulfur dioxide exposure and hospitalization costs of ischemic stroke: a hospital-based study in Chongqing, China.

Evidence of the short-term effects of ambient sulfur dioxide (SO2) exposure on the economic burden of ischemic stroke is limited. This study aimed to explore the association between short-term ambient SO2 exposure and hospitalization costs for ischemic stroke in Chongqing, the most populous city in China. The hospital-based study included 7271 ischemic stroke inpatients. Multiple linear regression models were used to estimate the association between SO2 concentration and hospitalization costs. Propensity score matching was used to compare the patients' characteristics when exposed to SO2 concentrations above and below 20 µg/m3. It is found that short-term SO2 exposure was positively correlated with the hospitalization costs of ischemic stroke. The association was more evident in males, people younger than 65, and people hospitalized in the cool seasons. Besides, among the components of hospitalization costs, medicine costs were most significantly associated with SO2. More interesting, the lower concentration of SO2, the higher costs associated with 1 µg/m3 SO2 change. Above all, SO2 was positively associated with hospitalization costs of ischemic stroke, even at its low levels. The measures to reduce the level of SO2 can help reduce the burden of ischemic stroke.

Lipopolysaccharide induces inflammatory microglial activation through CD147-mediated matrix metalloproteinase expression.

Microglia-mediated neuroinflammation plays a vital role in the pathophysiological processes of multiple neurodegenerative diseases. Lipopolysaccharide (LPS) is an environmental poison that can induce inflammatory microglial activation. Matrix metalloproteinases (MMPs) are vital factors regulating microglial activation, and CD147 is a key MMP inducer, which can induce inflammation by inducing MMPs. However, whether it is involved in the regulation of microglial activation has not been reported. In this study, the role of CD147 in LPS-induced microglial inflammatory activation was investigated by establishing in vivo and in vitro models. The results suggested that LPS-induced microglial activation was accompanied by the induction of CD147 expression while the inhibition of CD147 expression could inhibit LPS-induced microglial inflammatory activation. In addition, the results also indicated that the role of CD147 in LPS-induced pro-inflammatory activation of microglia was related to its downstream MMP-3, MMP-8, and autophagy. Furthermore, the inhibition of MMP-3, MMP-8, and autophagy attenuated LPS-induced inflammatory activation of microglia. At the same time, there was a certain interaction between MMPs and autophagy, which is shown that inhibiting the expression of MMPs could inhibit autophagy, whereas inhibiting autophagy could inhibit the expression of MMPs. Taken together, we provided the first evidence that CD147/MMPs can be involved in LPS-induced inflammatory activation of microglia through an autophagy-dependent manner.

Cystathionine γ-lyase mediates cell proliferation, migration, and invasion of nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is an epithelia-derived malignancy with a distinctive geographic distribution. Cystathionine γ-lyase (CSE) is involved in cancer development and progression. Nevertheless, the role of CSE in the growth of NPC is unknown. In this study, we found that CSE levels in human NPC cells were higher than those in normal nasopharyngeal cells. CSE overexpression enhanced the proliferative, migrative, and invasive abilities of NPC cells and CSE downregulation exerted reverse effects. Overexpression of CSE decreased the expressions of cytochrome C, cleaved caspase (cas)-3, cleaved cas-9, and cleaved poly-ADP-ribose polymerase, whereas CSE knockdown exhibited reverse effects. CSE overexpression decreased reactive oxygen species (ROS) levels and the expressions of phospho (p)-extracellular signal-regulated protein kinase 1/2, p-c-Jun N-terminal kinase, and p-p38, but promoted the expressions of p-phosphatidylinositol 3-kinase (PI3K), p-AKT, and p-mammalian target of rapamycin (mTOR), whereas CSE knockdown showed oppose effects. In addition, CSE overexpression promoted NPC xenograft tumor growth and CSE knockdown decreased tumor growth by modulating proliferation, angiogenesis, cell cycle, and apoptosis. Furthermore, DL-propargylglycine (an inhibitor of CSE) dose-dependently inhibited NPC cell growth via ROS-mediated mitogen-activated protein kinase (MAPK) and PI3K/AKT/mTOR pathways without significant toxicity. In conclusion, CSE could regulate the growth of NPC cells through ROS-mediated MAPK and PI3K/AKT/mTOR cascades. CSE might be a novel tumor marker for the diagnosis and prognosis of NPC. Novel donors/drugs that inhibit the expression/activity of CSE can be developed in the treatment of NPC.

Association between short-term ambient nitrogen dioxide and type 2 diabetes outpatient visits: A large hospital-based study.

Type 2 diabetes (T2DM) as a non-communicable disease imposes heavy disease burdens on society. Limited studies have been conducted to assess the effects of short-term air pollution exposure on T2DM, especially in Asian regions. Our research aimed to determine the association between short-term exposure to ambient nitrogen dioxide (NO2) and outpatient visits for T2DM in Chongqing, the largest city in western China, based on the data collected from November 28, 2013 to December 31, 2019. A generalized additive model (GAM) was applied, and stratified analyses were performed to investigate the potential modifying effects by age, gender, and season. Meanwhile, the disease burden was revealed from attributable risk. Positive associations between short-term NO2 and daily T2DM outpatient visits were observed. The strongest association was observed at lag 04, with per 10 µg/m3 increase of NO2 corresponded to increased T2DM outpatient visits at 1.57% [95% confidence interval (CI): 0.48%, 2.65%]. Stronger associations were presented in middle-aged group (35-64 years old), male group, and cool seasons (October to March). Moreover, there were 1.553% (8664.535 cases) of T2DM outpatient visits attributable to NO2. Middle-aged adults, males, and patients who visited in cool seasons suffered heavier burdens. Conclusively, short-term exposure to NO2 was associated with increased outpatient visits for T2DM. Attention should be paid to the impact of NO2 on the burden of T2DM, especially for those vulnerable groups.

Role of p53 methylation in manganese-induced cyclooxygenase-2 expression in BV2 microglial cells.

Manganese (Mn) is an essential cofactor for many enzymes and plays an important role in normal growth and development. However, excess exposure to manganese (Mn) may be an important environmental factor leading to neurodegeneration. The overexpression of microglial cyclooxygenase-2 (COX-2) plays a key role in neuroinflammation in neurodegenerative diseases. The existing data suggest that Mn can induce neuroinflammation by up-regulating COX-2 expression. However, the mechanisms involved in Mn-induced microglial COX-2 up-regulation remain to be determined. The aim of this study was to investigate the role of p53 in Mn-induced COX-2 expression in microglial cells. The results showed that Mn exposure induced the up-regulation of COX-2 and inhibited the expression of p53 in BV2 microglial cells. The addition of p53 activator and the over-expression of p53 blocked the expression of COX-2 and prostaglandin E2 (PGE2), a COX-2 downstream effector, induced by Mn. Further, Mn increased the methylation of p53 DNA in microglia, while the addition of demethylation reagent 5-Aza-dC enhanced the expression of p53 but decreased the expression of COX-2. These results suggested that Mn may inhibit p53 expression through induction of DNA methylation, which can further induce the expression of COX-2 in microglial cells.

Effect of lattice mismatch on film morphology of the quasi-one dimensional conductor K0.3MoO3.

High quality epitaxial thin films of the quasi-one dimensional conductor K0.3MoO3 have been successfully grown on SrTiO3(100), SrTiO3(110), and SrTiO3(510) substrates via pulsed laser deposition. Scanning electron microscopy revealed quasi-one dimensional rod-shaped structures parallel to the substrate surface, and the crystal structure was verified by using X-ray diffraction. The temperature dependence of the resistivity for the K0.3MoO3 thin films demonstrates a metal-to-semiconductor transition at about 180 K. Highly anisotropic resistivity was also observed for films grown on SrTiO3(510).