Sources, trigger points, and effect size of associations between PM2.5-bound polycyclic aromatic hydrocarbons (PAHs) and fractional exhaled nitric oxide (FeNO): A panel study with 16 follow-up visits over 4 years.

Exposure to fine particulate matter (PM2.5) is a significant concern for respiratory health. However, the sources, trigger points, and effect size of specific associations between PM2.5 components, particularly polycyclic aromatic hydrocarbons (PAHs) and the airway inflammatory marker fractional exhaled nitric oxide (FeNO) have not been fully explored. In this study, 69 healthy college students were enrolled and followed up 16 times from 2014 to 2018. Individual FeNO was measured and ambient air PM2.5 samples were collected for 7 consecutive days before each follow-up. PAHs were quantified using Gas Chromatography-Mass Spectrometry. Linear mixed-effect regression models were employed to evaluate the associations between PM2.5-bound PAHs and FeNO. Additionally, PMF (Positive Matrix Factorization) was utilized to identify sources of PM2.5-bound PAHs and assess their impact on FeNO. Throughout the study, the average (SD) of ΣPAHs concentrations was 78.50 (128.9) ng/m3. PM2.5 and PM2.5-bound PAHs were significantly associated with FeNO at various lag days. Single-day lag analyses revealed maximum effects of PM2.5 on FeNO, with an increase of 7.71% (95% CI: 4.67%, 10.83%) per interquartile range (IQR) (48.10 µg/m3) increase of PM2.5 at lag2, and ΣPAHs showed a maximum elevation in FeNO of 6.40% (95% CI: 2.33%, 10.63%) at lag4 per IQR (57.39 ng/m3) increase. Individual PAHs exhibited diversity peak effects on FeNO at lag3 (6 of 17), lag4 (9 of 17) in the single-day model, and lag0-5 (8 of 17) (from lag0-1 to lag0-6) in the cumulative model. Source apportionment indicated coal combustion as the primary contributor (accounting for 30.7%). However, a maximum effect on FeNO (an increase of 21.57% (95% CI: 13.58%, 30.13%) per IQR increase) was observed with traffic emissions at lag4. The findings imply that strategic regulation of particular sources of PAHs, like traffic emissions, during specific periods could significantly contribute to safeguarding public health.

Association between urinary arsenic species and vitamin D deficiency: a cross-sectional study in Chinese pregnant women.

Background: An increasing number of studies suggest that environmental pollution may increase the risk of vitamin D deficiency (VDD). However, less is known about arsenic (As) exposure and VDD, particularly in Chinese pregnant women. Objectives: This study examines the correlations of different urinary As species with serum 25 (OH) D and VDD prevalence. Methods: We measured urinary arsenite (As3+), arsenate (As5+), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) levels and serum 25(OH)D2, 25(OH)D3, 25(OH) D levels in 391 pregnant women in Tianjin, China. The diagnosis of VDD was based on 25(OH) D serum levels. Linear relationship, Logistic regression, and Bayesian kernel machine regression (BKMR) were used to examine the associations between urinary As species and VDD. Results: Of the 391 pregnant women, 60 received a diagnosis of VDD. Baseline information showed significant differences in As3+, DMA, and tAs distribution between pregnant women with and without VDD. Logistic regression showed that As3+ was significantly and positively correlated with VDD (OR: 4.65, 95% CI: 1.79, 13.32). Meanwhile, there was a marginally significant positive correlation between tAs and VDD (OR: 4.27, 95% CI: 1.01, 19.59). BKMR revealed positive correlations between As3+, MMA and VDD. However, negative correlations were found between As5+, DMA and VDD. Conclusion: According to our study, there were positive correlations between iAs, especially As3+, MMA and VDD, but negative correlations between other As species and VDD. Further studies are needed to determine the mechanisms that exist between different As species and VDD.

Serum Folate and Vitamin B12 Modify the Associations of N6AMT1 Genetic Variants with Gestational Diabetes Mellitus: A Cross-Sectional Study in Chinese Pregnant Women.

Purpose: This study aimed to explore the association between N-6 adenine-specific DNA methyltransferase 1 (N6AMT1) single nucleotide polymorphisms (SNPs) and gestational diabetes mellitus (GDM) and the modification of the relationship by folate and vitamin B12. Methods: A cross-sectional study involving 1303 pregnant women (262 GDM and 1041 non-GDM) was performed in Tianjin, China. Nine SNPs in N6AMT1 were genotyped, and serum folate, vitamin B12, and homocysteine (Hcy) levels were measured. The logistic regression models determined the odds ratios (ORs) for SNPs in N6AMT1 and the gene-nutrition interactions on GDM. Results: N6AMT1 rs7282280, rs1048546, and rs1997605 were related to GDM under the dominant model after adjusting for multiple covariates. Individuals carrying the N6AMT1 rs7282280 TC/TT genotypes had a lower risk of developing GDM, regardless of serum folate and vitamin B12 levels. However, rs1048546 TG/GG genotypes were associated with lower GDM risk when serum folate ≥ 6.0 ng/mL. Pregnancies with the risk genotypes in N6AMT1 and higher serum folate or lower vitamin B12 are more prone to GDM. The study also showed a statistically significant additive interaction between N6AMT1 rs1997605 GG genotypes and lower vitamin B12 (RERI: 2.54; 95% CI: 0.17, 4.92). Conclusion: SNPs in N6AMT1 were found to be associated with GDM, and serum folate and vitamin B12 levels can modify their associations.

Immune-related adverse events in non-small cell lung cancer: Occurrence, mechanisms and therapeutic strategies.

The emergence of immune checkpoint inhibitors (ICIs) has heralded a transformative era in the therapeutic landscape of non-small cell lung cancer (NSCLC). While ICIs have demonstrated clinical efficacy in a portion of patients with NSCLC, these treatments concurrently precipitate a spectrum of immune-related adverse events (irAEs), encompassing mild to severe manifestations, collectively posing a risk of significant organ damage. Consequently, there exists an imperative to augment our comprehension of the pathophysiological underpinnings of irAEs and to formulate more efficacious preventive and ameliorative strategies. In this comprehensive review, we delineate the clinical presentation of organ-specific irAEs in patients with NSCLC and provide an in-depth analysis of recent advancements in understanding the mechanisms driving ICI-induced toxicity. Furthermore, we discuss potential strategies and targets for ameliorating these irAEs. Ultimately, this review aims to furnish valuable insights to guide further research endeavours in the context of irAEs in NSCLC patients.

A stochastic programming approach for EOL electric vehicle batteries recovery network design under uncertain conditions.

With the development of the electric vehicle industry, the number of power batteries has increased dramatically. Establishing a recycling EOL (end-of-life) battery network for secondary use is an effective way to solve resource shortage and environmental pollution. However, existing networks are challenging due to the high uncertainty of EOL batteries, e.g., quantity and quality, resulting in a low recycling rate of the recovery network. To fill this gap, this paper proposes a stochastic programming approach for recovery network design under uncertain conditions of EOL batteries. Firstly, a multi-objective model for battery recovery network is established, considering carbon emissions and economic benefits. Secondly, a stochastic programming approach is proposed to clarify the model. Subsequently, the genetic algorithm is employed to solve the proposed model. Finally, a recovery network case of Region T is given to verify the credibility and superiority of the proposed method. The results demonstrate that the proposed model reduces carbon emissions by 20 metric tons and increases overall economic benefits by 10 million yuan in Region T compared to the deterministic model. Furthermore, the two portions affecting the optimization results are also discussed to provide a reference for reducing carbon emissions and improving economic efficiency in recycling networks.

Vitamin D and Its Receptors in Cervical Cancer.

Several studies have investigated the relationship between vitamin D (VD) and its receptors (VDR) and the risk of cervical cancer. However, the underlying mechanisms that underpin these associations remain incompletely comprehended. In this review, we analyzed the impacts of VD and VDR on cervical cancer and related mechanisms, and discussed the effects of VD, calcium, and other vitamins on cervical cancer. Our literature research found that VD, VDR and their related signaling pathways played indispensable roles in the occurrence and progression of cervical cancer. Epidemiological studies have established associations between VD, VDR, and cervical cancer susceptibility. Current studies have shown that the inhibitory effect of VD and VDR on cervical cancer may be attributed to a variety of molecules and pathways, such as the EAG potassium channel, HCCR-1, estrogen and its receptor, p53, pRb, TNF-α, the PI3K/Akt pathway, and the Wnt/ß-catenin pathway. This review also briefly discussed the association between VDR gene polymorphisms and cervical cancer, albeit a comprehensive elucidation of this relationship remains an ongoing research endeavor. Additionally, the potential ramifications of VD, calcium, and other vitamins on cervical cancer has been elucidated, yet further exploration into the precise mechanistic underpinnings of these potential effects is warranted. Therefore, we suggest that further studies should focus on explorations into the intricate interplay among diverse molecular pathways and entities, elucidation of the mechanistic underpinnings of VDR polymorphic loci changes in the context of HPV infection and VD, inquiries into the mechanisms of VD in conjunction with calcium and other vitamins, as well as investigations of the efficacy of VD supplementation or VDR agonists as part of cervical cancer treatment strategies in the clinical trials.

Multifunctional polydopamine/hemin-cyclodextrin reinforced chitosan nanocomposite hydrogel: A synergistic platform for wound healing.

Chronic cutaneous wounds present a significant challenge for healthcare providers globally, with the risk of bacterial infections emerging as a particularly concerning issue. There is an increasing need to employ a combination of diverse antibacterial strategies to address infections comprehensively in chronic wounds. This study introduces a highly efficient antibacterial platform that encapsulates the NO precursor (BNN6) into ß-cyclodextrin-modified hemin-bearing polydopamine nanoparticles called NO/CHPDA. These nanoparticles are seamlessly integrated into a hydrogel composite comprised of L-arginine grafted chitosan (Arg-CS) and oxide dextrans (oDex). The amalgamation of photothermal therapy (PTT), chemodynamic therapy (CDT), and nitric oxide (NO) antibacterial strategies within the NO/CHPDA@Arg-CS/oDex nanocomposite hydrogel demonstrates a synergistic and highly effective capacity to eradicate bacteria and accelerate the wound healing process in vivo. Remarkably, this nanocomposite hydrogel maintains excellent biocompatibility and induces minimal side effects. The resulting nanocomposite hydrogel represents a promising therapeutic solution for treating bacterial infections in wound healing applications.

Ambient PM2.5-bound polycyclic aromatic hydrocarbons (PAHs) associated with pro-thrombotic biomarkers among young healthy adults: A 16 times repeated measurements panel study.

Studies have shown that the cardio/cerebrovascular toxicity of ambient PM2.5 is related to its bound polycyclic aromatic hydrocarbons (PAHs). Currently, only a few studies have reported the relationship between PM2.5-bound PAHs and promoted blood coagulation and thrombosis, but there isn't a consistent conclusion. Therefore, we conducted a prospective panel study to investigate the association. Thirty-three young healthy adults participated in sixteen repeated visits from 2014 to 2018 in Tianjin, China. During each visit, three pro-thrombotic biomarkers: ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin motif 13), D-dimer and Myeloperoxidase (MPO) were measured. Before each visit, ambient PM2.5 samples were daily collected for one week. Sixteen PAHs were determined using Gas Chromatography-Mass Spectrometer, and the positive matrix factorization (PMF) model was applied to identify the sources. Linear mixed-effects models were fitted to investigate the associations between PM2.5-bound PAHs exposure and the biomarkers. Thirteen time-metrics were defined to identify significant time points of PM2.5-bound PAHs' effects. We observed that the increase of PM2.5-bound PAHs exposure was significantly associated with reduced ADAMTS13, elevated D-dimer and MPO. At lag0, each 5.7 ng/m3 increase in Benzo[j]fluoranthene and per 3.4 ng/m3 increase Dibenz[a,h]anthracene could make a maximum change of -19.08 % in ADAMTS13 and 132.60 % in D-dimer. Additionally, per 16.43 ng/m3 increase in Chrysene could lead to a maximum elevation of 32.14 % in MPO at lag4. The PM2.5-bound PAHs often triggered more significant changes at lag 3,4 and 6. The ambient PM2.5-bound PAHs originated from six sources: coal combustion (43.10 %), biomass combustion (20.77 %), diesel emission (14.78 %), gasoline emission (10.95 %), industrial emission (7.58 %), and cooking emission (2.83 %). The greatest contributors to alterations in ADAMTS13, D-dimer and MPO are industrial emission (-48.43 %), biomass combustion (470.32 %) and diesel emission (13.14 %) at lag4. Our findings indicated that short-term exposure to ambient PM2.5-bound PAHs can induce alterations of pro-thrombotic biomarkers among healthy adults.

Metabolic biomarkers linking urinary arsenic species to gestational diabetes mellitus: A cross-sectional study in Chinese pregnant women.

Environmental arsenic (As) exposure has been associated with gestational diabetes mellitus (GDM) risk. Our recent study found that GDM was positively associated with urinary As3+ level while negatively correlated to As5+. However, the mechanisms underlying the association between arsenic species and GDM remain largely unknown. In the present study, through the measurement of urinary arsenic species and metabolome analysis in 399 pregnant women, we aimed to identify the metabolic biomarkers that may link arsenic exposure to GDM based on a novel systems epidemiology strategy termed meet-in-metabolite-analysis (MIMA). The metabolomics analysis revealed that 20 and 16 urinary metabolites were relevant to arsenic exposure and GDM, respectively. Among them, 12 metabolites were identified to be both arsenic- and GDM-related, which are mainly involved in purine metabolism, one­carbon metabolism (OCM) and glycometabolism. Moreover, it was further showed that the regulation of thiosulfate (AOR: 2.52; 95 % CI: 1.33, 4.77) and phosphoroselenoic acid (AOR: 2.35; 95 % CI: 1.31, 4.22) could significantly contribute to the negative association between As5+ and GDM. Considering the biological functions of these metabolites, it is suggested that As5+ may reduce GDM risk by disturbing OCM in the pregnant women. These data will provide novel insights into the mechanism of action of environmental arsenic exposure on GDM incidence from the aspect of metabolism disorder.

Effects of Terahertz Radiation on the Aggregation of Alzheimer's Aß42 Peptide.

The pathophysiology of Alzheimer's disease is thought to be directly linked to the abnormal aggregation of ß-amyloid (Aß) in the nervous system as a common neurodegenerative disease. Consequently, researchers in many areas are actively looking for factors that affect Aß aggregation. Numerous investigations have demonstrated that, in addition to chemical induction of Aß aggregation, electromagnetic radiation may also affect Aß aggregation. Terahertz waves are an emerging form of non-ionizing radiation that has the potential to affect the secondary bonding networks of biological systems, which in turn could affect the course of biochemical reactions by altering the conformation of biological macromolecules. As the primary radiation target in this investigation, the in vitro modeled Aß42 aggregation system was examined using fluorescence spectrophotometry, supplemented by cellular simulations and transmission electron microscopy, to see how it responded to 3.1 THz radiation in various aggregation phases. The results demonstrated that in the nucleation aggregation stage, 3.1 THz electromagnetic waves promote Aß42 monomer aggregation and that this promoting effect gradually diminishes with the exacerbation of the degree of aggregation. However, by the stage of oligomer aggregation into the original fiber, 3.1 THz electromagnetic waves exhibited an inhibitory effect. This leads us to the conclusion that terahertz radiation has an impact on the stability of the Aß42 secondary structure, which in turn affects how Aß42 molecules are recognized during the aggregation process and causes a seemingly aberrant biochemical response. Molecular dynamics simulation was employed to support the theory based on the aforementioned experimental observations and inferences.

Serum folate mediates the associations of MTHFR rs1801133 polymorphism with blood glucose levels and gestational diabetes mellitus in Chinese Han pregnant women.

This study aimed to explore the mediation effects of one-carbon metabolism (OCM) related nutrients on the association between MTHFR rs1801133 polymorphism and gestational diabetes mellitus (GDM). Folate, vitamin B12 and homocysteine (Hcy) were measured in the serum of 1254 pregnant women. Linear and logistic regressions were used to estimate the associations of OCM nutrients and MTHFR rs1801133 polymorphism with blood glucose levels and GDM risk. Mediation analysis was applied to test the mediation effects of folate, vitamin B12 and Hcy on the association of MTHFR rs1801133 polymorphism with blood glucose concentrations and GDM. Pregnant women with MTHFR rs1801133 CC genotype had higher serum folate (10·75 v. 8·90 and 9·40 ng/ml) and lower serum Hcy (4·84 v. 4·93 and 5·20 µmol/l) than those with CT and TT genotypes. Folate concentrations were positively associated with fasting plasma glucose (FPG), 1-h plasma glucose (1-h PG), 2-h plasma glucose (2-h PG) and GDM risk. Vitamin B12 levels were negatively correlated with FPG and GDM. Although no direct association was found between MTHFR rs1801133 genotypes and GDM, there were significant indirect effects of MTHFR rs1801133 CC genotype on FPG (ß: 0·005; 95 % CI: 0·001, 0·013), 1-h PG (ß: 0·006; 95 % CI: 0·001, 0·014), 2-h PG (ß: 0·007; 95 % CI: 0·001, 0·015) and GDM (ß: 0·006; 95 % CI: 0·001, 0·014) via folate. In conclusion, serum folate mediates the effect of MTHFR rs1801133 on blood glucose levels and GDM. Our findings potentially provide a feasible GDM prevention strategy via individualised folate supplementation according to the MTHFR genotypes.

Folic acid deficiency exacerbates the inflammatory response of astrocytes after ischemia-reperfusion by enhancing the interaction between IL-6 and JAK-1/pSTAT3.

AIM: To demonstrate the role of IL-6 and pSTAT3 in the inflammatory response to cerebral ischemia/reperfusion following folic acid deficiency (FD). METHODS: The middle cerebral artery occlusion/reperfusion (MCAO/R) model was established in adult male Sprague-Dawley rats in vivo, and cultured primary astrocytes were exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) to emulate ischemia/reperfusion injury in vitro. RESULTS: Glial fibrillary acidic protein (GFAP) expression significantly increased in astrocytes of the brain cortex in the MCAO group compared to the SHAM group. Nevertheless, FD did not further promote GFAP expression in astrocytes of rat brain tissue after MCAO. This result was further confirmed in the OGD/R cellular model. In addition, FD did not promote the expressions of TNF-α and IL-1ß but raised IL-6 (Peak at 12 h after MCAO) and pSTAT3 (Peak at 24 h after MCAO) levels in the affected cortices of MCAO rats. In the in vitro model, the levels of IL-6 and pSTAT3 in astrocytes were significantly reduced by treatment with Filgotinib (JAK-1 inhibitor) but not AG490 (JAK-2 inhibitor). Moreover, the suppression of IL-6 expression reduced FD-induced increases in pSTAT3 and pJAK-1. In turn, inhibited pSTAT3 expression also depressed the FD-mediated increase in IL-6 expression. CONCLUSIONS: FD led to the overproduction of IL-6 and subsequently increased pSTAT3 levels via JAK-1 but not JAK-2, which further promoted increased IL-6 expression, thereby exacerbating the inflammatory response of primary astrocytes.

Arsenic metabolism, N6AMT1 and AS3MT single nucleotide polymorphisms, and their interaction on gestational diabetes mellitus in Chinese pregnant women.

BACKGROUND: Single nucleotide polymorphisms (SNPs) in N6AMT1 and AS3MT are associated with arsenic (As) metabolism, and efficient As methylation capacity has been associated with diabetes. However, little is known about the gene-As interaction on gestational diabetes mellitus (GDM). OBJECTIVE: This study aimed to explore the individual and combined effects of N6AMT1 and AS3MT SNPs with As metabolism on GDM. METHODS: A cross-sectional study was performed among 385 Chinese pregnant women (86 GDM and 299 Non-GDM). Four SNPs in N6AMT1 (rs1997605 and rs1003671) and AS3MT (rs1046778 and rs11191453) were genotyped. Urinary inorganic arsenic (iAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) were determined, and the percentages of As species (iAs%, MMA%, and DMA%) were calculated to assess the efficiency of As metabolism. RESULTS: Pregnant women with N6AMT1 rs1997605 AA genotype had lower iAs% (B: 2.11; 95% CI: 4.08, -0.13) and MMA% (B: 0.21; 95% CI: 0.39, -0.04) than pregnant women with GG genotype. The AS3MT rs1046778 and rs11191453 C alleles were negatively associated with iAs% and MMA% but positively associated with DMA%. Higher urinary MMA% was significantly associated with a lower risk of GDM (OR: 0.54; 95% CI: 0.30, 0.97). The A allele in N6AMT1 rs1997605 (OR: 0.46; 95% CI: 0.26, 0.79) was associated with a decreased risk of GDM. The additive interactions between N6AMT1 rs1997605 GG genotypes and lower iAs% (AP: 0.50; 95% CI: 0.01, 0.99) or higher DMA% (AP: 0.52; 95% CI: 0.04, 0.99) were statistically significant. Similar additive interactions were also found between N6AMT1 rs1003671 GG genotypes and lower iAs% or higher DMA%. CONCLUSIONS: Genetic variants in N6AMT1 and efficient As metabolism (indicated by lower iAs% and higher DMA%) can interact to influence GDM occurrence synergistically in Chinese pregnant women.

Astaxanthin delays brain aging in senescence-accelerated mouse prone 10: inducing autophagy as a potential mechanism.

Brain aging is a complex biological process often associated with a decline in cognitive functions and motility. Astaxanthin (AST) is a strong antioxidant capable of crossing the blood-brain barrier. The effect of AST on brain aging and its physiological and molecular mechanism are still unclear. The study aimed to investigate whether AST from AstaReal A1010 improved brain aging by inducing autophagy in SAMP10 mice. Different concentrations of AstaReal A1010 were intragastrically administered to 6-month-old SAMP10 mice for 3 months. The results demonstrated that AST delayed age-related cognitive decline, motor ability and neurodegeneration, upregulated the expression levels of autophagy-related genes beclin-1 and LC3 in the brain. It may induce autophagy by regulating IGF-1/Akt/mTOR and IGF-1/Akt/FoxO3a signaling. Treatment with autophagy inhibitor 3-methyladenine (3MA) partly reversed the anti-aging effect of AST. In conclusion, our findings suggest that AST may induce autophagy by regulating IGF-1/Akt/mTOR and IGF-1/Akt/FoxO3a signaling, thereby delaying age-related neurodegeneration and cognitive decline in SAMP10 mice.

Homocysteine can aggravate depressive like behaviors in a middle cerebral artery occlusion/reperfusion rat model: a possible role for NMDARs-mediated synaptic alterations.

BACKGROUND: Post-stroke depression (PSD), the most frequent psychiatric complication following stroke, could have a negative impact on the recuperation of stroke patients. Hyperhomocysteinemia (HHCY) has been reported to be a modifiable risk factor of stroke. OBJECTIVE: The study tries to explore the effect of HHCY on PSD and the role of N-methyl-d-aspartate receptors (NMDARs)-mediated synaptic alterations. METHODS: Forty-five adult male Sprague-Dawley rats were randomly allocated into five groups: sham operation group, middle cerebral artery occlusion group (MCAO), HCY-treated MCAO group HCY and MK-801 co-treated MCAO group and MK-801-treated MCAO group. 1.6 mg/kg/d D, L-HCY was administered by tail vein injection for 28 d prior to SHAM or MCAO operationand up to 14 d after surgery. The MK-801 (3 mg/kg) was administered by intraperitoneal injection 15 min prior to MCAO operation. RESULTS: HCY treatment aggravated depressive-like disorders of post-stroke rats by the open field test and sucrose preference test. Further, HCY significantly decreased central monoamines levels in the MCAO rats by HPLC. The transmission electron microscopy results showed that the number of synapses and the area of postsynaptic density decreased in the hippocampus of the HCY-treated MCAO rats. Additionally, HCY augmented ischemia-induced up-regulation of NMDARs, decreased the levels of synaptic structure-related marker PSD-95and the synaptic transmission-associated synaptic proteins (VGLUT1, SNAP-25 and Complexin Ι/ΙΙ). These effects of HCY were partly reversed by the NMDA antagonist MK-801. CONCLUSIONS: The current study suggested that NMDARs-mediated synaptic plasticity may be involved in the adverse effect of HCY on PSD.

Folic acid ameliorates synaptic impairment following cerebral ischemia/reperfusion injury via inhibiting excessive activation of NMDA receptors.

Folic acid, a water-soluble B-vitamin, has been demonstrated to decrease the risk of first stroke and improve its poor prognosis. However, the molecular mechanisms responsible for the beneficial effect of folic acid on recovery from ischemic insult remain largely unknown. Excessive activation of the N-methyl-d-aspartate receptors (NMDARs) has been shown to trigger synaptic dysfunction and excitotoxic neuronal death in ischemic brains. Here, we hypothesized that the effects of folic acid on cognitive impairment may involve the changes in synapse loss and NMDAR expression and function following cerebral ischemia/reperfusion injury. The ischemic stroke models were established by middle cerebral artery occlusion/reperfusion (MCAO/R) and by oxygen-glucose deprivation and reperfusion (OGD/R)-treated primary neurons. The results showed that folic acid supplemented diets (8.0 mg/kg for 28 days) improved cognitive performances of rats after MCAO/R. Folic acid also caused a reduction in the number of neuronal death, an increase in the number of synapses and the expressions of synapse-related proteins including SNAP25, Syn, GAP-43 and PSD95, and a decrease in p-CAMKII expression in ischemic brains. Similar changes in synaptic functions were observed in folic acid (32 µM)-treated OGD/R neurons. Furthermore, NMDA treatment reduced folic acid-induced upregulations of synapse-associated proteins and Ca2+ influx, whereas downregulations of NMDARs by NR1 or both NR2A and NR2B siRNA further enhanced the expressions of synapse-related proteins raised by folic acid in OGD/R neurons. Our findings suggest that folic acid improves cognitive dysfunctions and ameliorates ischemic brain injury by strengthening synaptic functions via the NMDARs.

An Energy Data-Driven Approach for Operating Status Recognition of Machine Tools Based on Deep Learning.

Machine tools, as an indispensable equipment in the manufacturing industry, are widely used in industrial production. The harsh and complex working environment can easily cause the failure of machine tools during operation, and there is an urgent requirement to improve the fault diagnosis ability of machine tools. Through the identification of the operating state (OS) of the machine tools, defining the time point of machine tool failure and the working energy-consuming unit can be assessed. In this way, the fault diagnosis time of the machine tool is shortened and the fault diagnosis ability is improved. Aiming at the problems of low recognition accuracy, slow convergence speed and weak generalization ability of traditional OS recognition methods, a deep learning method based on data-driven machine tool OS recognition is proposed. Various power data (such as signals or images) of CNC machine tools can be used to recognize the OS of the machine tool, followed by an intuitive judgement regarding whether the energy-consuming units included in the OS are faulty. First, the power data are collected, and the data are preprocessed by noise reduction and cropping using the data preprocessing method of wavelet transform (WT). Then, an AlexNet Convolutional Neural Network (ACNN) is built to identify the OS of the machine tool. In addition, a parameter adaptive adjustment mechanism of the ACNN is studied to improve identification performance. Finally, a case study is presented to verify the effectiveness of the proposed approach. To illustrate the superiority of this method, the approach was compared with traditional classification methods, and the results reveal the superiority in the recognition accuracy and computing speed of this AI technology. Moreover, the technique uses power data as a dataset, and also demonstrates good progress in portability and anti-interference.

Association between Dietary Patterns and the Risk of Depressive Symptoms in the Older Adults in Rural China.

Geriatric depression, a chronic condition, has become a substantial burden in rural China. This study aimed to assess the association between dietary patterns and the risk of geriatric depression in rural China. Between March 2018 and June 2019, 3304 participants were recruited for this cross-sectional study in rural Tianjin, China. Principal component analysis was used to determine the major dietary patterns. The associations between dietary patterns and the risk of geriatric depression were assessed using a logistic regression model. Four dietary patterns were identified: vegetables-fruit, animal food, processed food, and milk-egg. The study found that vegetable-fruit (Q2 vs. Q1: OR = 0.62, 95% CI: 0.46-0.83; Q3 vs. Q1: OR = 0.54, 95% CI: 0.38-0.75; Q4 vs. Q1: OR = 0.39, 95% CI: 0.26-0.57) and animal food patterns (Q3 vs. Q1: OR = 0.69, 95% CI: 0.50-0.95; Q4 vs. Q1: OR = 0.58, 95% CI: 0.41-0.82) were associated with a decreased risk of depression, and inflammatory dietary pattern (Q2 vs. Q1: OR = 1.71, 95% CI: 1.23-2.38; Q3 vs. Q1: OR = 1.70, 95% CI: 1.22-2.36; Q4 vs. Q1: OR = 1.44, 95% CI: 1.03-2.03) was associated with an increased risk of depression. The present findings reinforce the importance of adopting an adequate diet consisting of vegetables, fruit and animal foods, while limiting the intake of pro-inflammatory foods, to decrease the risk of depression.

Circulating folate concentrations and the risk of mild cognitive impairment: A prospective study on the older Chinese population without folic acid fortification.

BACKGROUND: The longitudinal association between serum folate concentrations and the risk of cognitive impairment remains unclear in populations with low folate levels. We examined the association between serum folate concentrations and mild cognitive impairment (MCI) in older adults in China, where mandatory fortification of foods with folic acid has not been implemented. We further explored if homocysteine (Hcy) and leukocyte telomere length (LTL) mediate the association between serum folate and MCI. METHODS: We performed a longitudinal analysis of 3974 participants aged ≥60 years from the Tianjin Elderly Nutrition and Cognition (TENC) cohort study. The associations between serum folate level and the risk of cognitive impairment overall and stratified by apolipoprotein E (APOE) ε4 genotypes were evaluated using multivariable Cox proportional hazards models. The mediating effects of Hcy and LTL on the folate-MCI association were explored via a path analysis approach. RESULTS: Within a 3-year follow-up, we documented 560 incident MCI cases. After multivariable adjustment, higher serum folate concentrations were associated with lower incidence of MCI, with hazard ratios (95% confidence interval) across quartiles of folate (from lowest to highest concentrations) of 1.00 (reference), 0.66 (0.52, 0.83), 0.57 (0.45, 0.73), 0.66 (0.52, 0.84), respectively (p for trend <0.001). In mediation analyses, the status of serum folate deficiency and MCI were correlated via two intermediary pathways, Hcy and Hcy-telomere (p < 0.05). CONCLUSIONS: Lower folate concentrations, independently of APOE genotype, were associated with increased risk of MCI among elderly Chinese people, a population with relatively low folate intake. Our data were compatible with the mediation hypothesis that the association between folate status and MCI was mediated by Hcy and LTL.

Associations of Maternal rs1801131 Genotype in MTHFR and Serum Folate and Vitamin B12 with Gestational Diabetes Mellitus in Chinese Pregnant Women.

Circumstantial evidence links one-carbon metabolism (OCM) related nutrients, such as folate and vitamin B12, with gestational diabetes mellitus (GDM). However, few studies have evaluated the combined effects of these nutrients with OCM related gene polymorphisms on GDM. This study investigated whether OCM related genetic variants modified the associations of folate and B12 with GDM. Logistic regression was used to estimate odds ratios (ORs) for OCM related nutrients and single nucleotide polymorphisms (SNPs) in genes encoding main OCM related enzymes (MTHFR, MTR, and MTRR) on GDM. Higher folate concentrations were associated with increased GDM risk (OR: 1.59; 95% CI: 1.22, 2.13). However, higher B12 concentrations were associated with reduced GDM risk (OR: 0.76; 95% CI: 0.65, 0.92). Pregnancies with MTHFR rs1801131 G alleles had a significantly lower risk of GDM than pregnancies with T alleles (OR: 0.65; 95% CI: 0.47, 0.91) under the dominant model. The genotype-stratified analysis revealed the association between folate and GDM (OR: 1.66, 95% CI: 1.20, 2.30) or B12 and GDM (OR: 0.80, 95% CI: 0.65, 0.98) was more evident in pregnancies with TT genotype. Higher folate and lower B12 are associated with GDM. Pregnancies with MTHFR rs1801131 TT genotype are more susceptible to OCM nutrient-related GDM.