The genotoxicity impact of heavy metals on the Escherichia coli.

In present work, the genotoxicity of Hg2+, Ag+, Cr6+, Ni2+, Pb2+, Co2+, Mn2+, Zn2+, and Cr3+ was investigated via a quantitative toxicogenomics assay, to understand the toxic mechanism of heavy metals with greater depth. Under the experimental conditions, Hg2+, Ag+, and Cr6+ showed a more serious toxic impact on the expression of functional genes (eg., oxyR, katG, grxA, osmE, emrE, dinG) than Ni2+, Pb2+, Co2+, Mn2+, Zn2+, and Cr3+, while the protein, oxidative, and membrane stress response pathways were more sensitive to the toxicity of Hg2+, Ag+, and Cr6+ than the DNA and general stress response pathways. Compared with the other kinds of heavy metals, Ni2+, Pb2+, Co2+, and Mn2+ altered the expression of functional genes (uvrY, recX, mutY, and sbmC) related to the DNA stress response pathways more seriously, while Zn2+ and Cr3+ changed the expression of the functional genes (yfjG, ydgL, ssrA, and osmC) associated with the general stress response pathway more significantly. Meanwhile, the toxicity of Ni2+, Pb2+, Co2+, and Mn2+ was slightly higher than that of Zn2+ and Cr3+ in terms of the total value of transcriptional effect level Index (TELI) by detecting the promoter activities of different functional genes. In addition, to survive the toxicity of heavy metals, the expression of multidrug efflux genes (ydgL, cyoA, emrA, and emrE) and toxicity-resistant genes (Ion, dnaJ, clpB, mutY, dnaK, rpoD, sbmC) mainly functioned.

SNHG3/miR-330-5p/HSD11B1 Alleviates Myocardial Ischemia-reperfusion Injury by Regulating the ERK/p38 Signaling Pathway.

BACKGROUND: Studies have found that microRNAs (miRNAs) participate in the pathogenesis of myocardial ischemia-reperfusion injury (MIRI). miR-330-5p alleviated cerebral IR injury and regulated myocardial damage. However, the mechanism of the effect of miR-330-5p on MIRI needs to be further studied. OBJECTIVE: The study aimed to explore the role and mechanism of miR-330-5p in MIRI. METHODS: The oxygen-glucose deprivation reperfusion (OGD/R) model was constructed in cardiomyocytes to simulate MIRI in vitro. QRT-PCR was used for the detection of gene expression. ELISA was used for evaluation of the levels of aldehyde dehydrogenase 2 family member (ALDH2), 4-hydroxynonenal (4-HNE), and malondialdehyde (MDA). Flow cytometry was used to evaluate apoptosis. Western blot was employed for protein determination. Bioinformatic analysis was performed for predicting the targets of miR-330-5p. RESULTS: miR-330-5p was found to be down-regulated in MIRI-induced cardiomyocytes (Model group). miR-330-5p mimic enhanced ALDH2 activity, inhibited apoptosis, and suppressed 4-HNE and MDA of MIRI-induced cardiomyocytes. miR-330-5p inhibited ERK expression while increasing the p38 expression. Bioinformatic analysis showed hydroxysteroid 11-beta dehydrogenase 1 (HSD11B1) to be a target of miR-330-5p. HSD11B1 expression was inhibited by miR-330-5p mimic while increased by miR-330-5p inhibitor in MIRI-induced cardiomyocytes. HSD11B1 overexpression reversed the effect of miR-330-5p on ALDH2, 4-HNE, MDA, apoptosis, and ERK/p38 signaling pathway. Furthermore, lncRNA small nucleolar RNA host gene 3 (SNHG3) was the upstream lncRNA of miR-330-5p. SNHG3 decreased miR-330-5p expression and increased HSD11B1 expression. CONCLUSION: SNHG3/miR-330-5p alleviated MIRI in vitro by targeting HSD11B1 to regulate the ERK/p38 signaling pathway.

Face mask derived micro(nano)plastics and organic compounds potentially induce threat to aquatic ecosystem security revealed by toxicogenomics-based assay.

Micro(nano)plastics widely detected in aquatic environments have caused serious threat to water quality security. However, as a potential important source of micro(nano)plastics in surface water during the COVID-19 pandemic, the ecological risks of face mask waste to aquatic environments remain poorly understood. Herein, we comprehensively characterized the micro(nano)plastics and organic compounds released from four daily used face masks in aqueous environments and further evaluated their potential impacts on aquatic ecosystem safety by quantitative genotoxicity assay. Results from spectroscopy and high-resolution mass spectrum showed that plastic microfibers/particles (∼11%-83%) and leachable organic compounds (∼15%-87%) were dominantly emitted pollutants, which were significantly higher than nanoplastics (< ∼5%) based on mass of carbon. Additionally, a toxicogenomics approach using green fluorescence protein-fused whole-cell array revealed that membrane stress was the primary response upon the exposure to micro(nano)plastics, whereas the emitted organic chemicals were mainly responsible for DNA damage involving most of the DNA repair pathways (e.g., base/nucleotide excision repair, mismatch repair, double-strand break repair), implying their severe threat to membrane structure and DNA replication of microorganisms. Therefore, the persistent release of discarded face masks derived pollutants might exacerbate water quality and even adversely affect aquatic microbial functions. These findings would contribute to unraveling the potential effects of face mask waste on aquatic ecosystem security and highlight the necessity for more developed management regulations in face mask disposal.

The toxicity assessment of 14 biocides for industrial circulating cooling water system by damage/repair pathway profiling analysis.

The toxicity of 14 biocides commonly used in circulating cooling water systems were evaluated. Results showed that biocide exposure can induce complex damage/repair pathways, including DNA, oxidative, protein, general, and membrane stress. All damages enhanced with increasing concentrations. Among them, MTC exhibited toxicity at concentrations as low as 1.00 × 10-17 mg/L, and TELItotal reached 1.60. We derived molecular toxicity endpoints based on dose-response curves to compare the normalized toxicity of biocides. Total-TELI1.5 exhibited that THPS, MTC, and DBNPA have the lowest toxic exposure concentrations, which are 2.180 × 10-27, 1.015 × 10-14, and 3.523 × 10-6 mg/L. TBTC, MTC, and 2,4-DCP had the highest Total-TELImax values, which are 861.70, 526.30, and 248.30. Moreover, there was a high correlation (R2 =0.43-0.97) between biocides' molecular structure and toxicity. And, biocide exposure combinations were found to increase toxicity pathways and enhance toxic effects, with a similar toxicity mechanism observed as in single-component exposure.

Acute impact of salinity and C/N ratio on the formation and properties of soluble microbial products from activated sludge.

The present study investigated the shock of NaCl and C/N ratio on properties of soluble microbial products (SMPs), focusing on their sized fractions. The results indicated that the NaCl stress increased the content of biopolymers, humic substances, building blocks, and LMW substances in SMPs, while the addition of 40 g NaCl L-1 significantly changed their relative abundance in SMPs. The acute impact of both N-rich and N-deficient conditions accelerated the secretion of SMPs, but the characteristics of LMW substances differed. Meanwhile, the bio-utilization of SMPs has been enhanced with the increase of NaCl dosage but decreased with the increase of the C/N ratio. The mass balance of sized fractions in SMPs + EPS could be set up when NaCl dosage <10 g/L and C/N ratio >5, which indicates the hydrolysis of sized fractions in EPS mainly compensated for their increase/reduction in SMPs. Besides, the results of the toxic assessment indicated that the oxidative damage caused by the NaCl shock was an important factor affecting the property of SMPs, and the abnormal expression of DNA transcription cannot be neglected for bacteria metabolisms with the change of C/N ratio.

UV-induced microplastics (MPs) aging leads to comprehensive toxicity.

Herein, the toxicity of 4 MPs and additives released from MPs during UV-aging was quantitatively evaluated by the transcriptional effect level index (TELI) based on E. coli whole-cell microarray assay, and MPs-antibiotics complex pollutants. Results showed that MPs and these additives had high toxicity potential, the maximum TELI was 5.68/6.85 for polystyrene (PS)/bis(2-ethylhexyl) phthalate (DEHP). There were many similar toxic pathways between MPs and additives, indicating that part of the toxicity risk of MPs was caused by the release of additives. MPs were compounded with antibiotics, the toxicity value changed significantly. The TELI values of amoxicillin (AMX) + polyvinyl chloride (PVC) and ciprofloxacin (CIP) + PVC were as high as 12.30 and 14.58 (P < 0.05). Three antibiotics all decreased the toxicity of PS and had little effect on polypropylene (PP) and polyethylene (PE). The combined toxicity mechanism of MPs and antibiotics was very complicated, and the results could be divided into four types: MPs (PVC/PE + CIP), antibiotics (PVC + TC, PS + AMX/ tetracycline (TC)/CIP, PE + TC), both (PP + AMX/TC/CIP), or brand-new mechanisms (PVC + AMX).

Association between healthy lifestyle and memory decline in older adults: 10 year, population based, prospective cohort study.

OBJECTIVE: To identify an optimal lifestyle profile to protect against memory loss in older individuals. DESIGN: Population based, prospective cohort study. SETTING: Participants from areas representative of the north, south, and west of China. PARTICIPANTS: Individuals aged 60 years or older who had normal cognition and underwent apolipoprotein E (APOE) genotyping at baseline in 2009. MAIN OUTCOME MEASURES: Participants were followed up until death, discontinuation, or 26 December 2019. Six healthy lifestyle factors were assessed: a healthy diet (adherence to the recommended intake of at least 7 of 12 eligible food items), regular physical exercise (≥150 min of moderate intensity or ≥75 min of vigorous intensity, per week), active social contact (≥twice per week), active cognitive activity (≥twice per week), never or previously smoked, and never drinking alcohol. Participants were categorised into the favourable group if they had four to six healthy lifestyle factors, into the average group for two to three factors, and into the unfavourable group for zero to one factor. Memory function was assessed using the World Health Organization/University of California-Los Angeles Auditory Verbal Learning Test, and global cognition was assessed via the Mini-Mental State Examination. Linear mixed models were used to explore the impact of lifestyle factors on memory in the study sample. RESULTS: 29 072 participants were included (mean age of 72.23 years; 48.54% (n=14 113) were women; and 20.43% (n=5939) were APOE ε4 carriers). Over the 10 year follow-up period (2009-19), participants in the favourable group had slower memory decline than those in the unfavourable group (by 0.028 points/year, 95% confidence interval 0.023 to 0.032, P<0.001). APOE ε4 carriers with favourable (0.027, 95% confidence interval 0.023 to 0.031) and average (0.014, 0.010 to 0.019) lifestyles exhibited a slower memory decline than those with unfavourable lifestyles. Among people who were not carriers of APOE ε4, similar results were observed among participants in the favourable (0.029 points/year, 95% confidence interval 0.019 to 0.039) and average (0.019, 0.011 to 0.027) groups compared with those in the unfavourable group. APOE ε4 status and lifestyle profiles did not show a significant interaction effect on memory decline (P=0.52). CONCLUSION: A healthy lifestyle is associated with slower memory decline, even in the presence of the APOE ε4 allele. This study might offer important information to protect older adults against memory decline. TRIAL REGISTRATION: ClinicalTrials.gov NCT03653156.

Adsorption of antibiotics on different microplastics (MPs): Behavior and mechanism.

MPs can adsorb antibiotics to coexist and accumulate in the aquatic environment in the form of complexes, resulting in unforeseeable adverse consequences. The adsorption behavior and mechanism of three antibiotics amoxicillin (AMX), ciprofloxacin (CIP), and tetracycline (TC) by four MPs Polyvinyl chloride (PVC), polystyrene (PS), polypropylene (PP), and polyethylene (PE) were studied. Results showed that the adsorption of antibiotics onto MPs follows the pseudo-second-order kinetic and the Freundlich isotherm model, indicating a multilayer chemical adsorption. Combined with FTIR, XRD, and SEM analyses, the adsorption behavior was simultaneously governed by physical processes. Additionally, the equilibrium adsorption capacity was inhibited in the research concentration range of NaCl from 10 mg/L to 10 g/L. The higher the salt concentration, the more pronounced the inhibition phenomenon was. The high (9) and low (3) pH also inhibited the adsorption of antibiotics to MPs. The humic acid (HA) concentration in the range of 0-20 mg/L generally inhibited the MPs-antibiotics adsorption, but the higher HA concentration showed less inhabitation than the lower one. The adsorption inhibition of TC on the four MPs by SA also followed the above rule. However, the adsorption inhibition of sodium alginate (SA) on AMX and CIP on the four MPs was enhanced with its concentration (0-50 mg/L).

Variation of the toxicity caused by key contaminants in industrial wastewater along the treatment train of Fenton-activated sludge-advanced oxidation processes.

Industrial wastewater contains a mixture of refractory and hazardous pollutants that have comprehensive toxic effects. We investigated the treatment of a long-chain industrial wastewater treatment train containing Fenton, biological anoxic/oxic (AO), and heterogeneous ozone catalytic oxidation (HOCO) processes, and evaluated their detoxification effect based on the analysis of the genic toxicity of some key contaminants. The results showed that although the effluent met the discharge standard in terms of traditional quality parameters, the long-chain treatment process could not effectively detoxify the industrial wastewater. The analysis results of summer samples showed that the Fenton process increased the total toxicity and genotoxicity of the organics, concerned metals, and non-volatile pollutants, whereas the A/O process increased the toxicity of the organics and non-volatile pollutants, and the HOCO process led to higher toxicity caused by metals and non-volatile pollutants. The outputs of the winter samples indicated that the Fenton process reduced the total toxicity and genotoxicity caused by non-volatile pollutants but increased that of the organics and concerned metals. The effect of the A/O process on the effluent toxicity in winter was the same as that in summer, whereas the HOCO process increased the total toxicity and genotoxicity of the metals in winter samples. Correlation analysis showed that various toxicity stresses were significantly correlated with the variation of these key pollutants in wastewater. Our results could provide a reference for the optimization of industrial wastewater treatment plants (IWTPs) by selecting more suitable treatment procedures to reduce the toxicity of different contaminants.

Comparing the toxicity of iodinated X-ray contrast media on eukaryote- and prokaryote-based quantified microarray assays.

This study compared the toxicity mechanisms of four X-ray-based iodinated contrast media (ICM) on Escherichia coli (E. coli) and yeast microarray assays, aiming to determine the diverse toxicity mechanisms among different exposed organisms and the relationship between toxicity and their physical and chemical characteristics. The conventional phenotypic endpoint cytotoxicity and the change in reactive oxygen species (ROS) level were employed in conjunction with toxicogenomics to quantify changes in the gene/protein biomarker level in the regulation of different damage/repair pathways. The results showed that molecular toxicity endpoints, named transcriptional effect level index (TELI) and protein effect level index (PELI) for E. coli and yeast, respectively, correlated well with the phenotypic endpoints. Temporal altered gene/protein expression profiles revealed dynamic and complex damage/toxic mechanisms. In particular, compared with E. coli cells, yeast cells exposed to ICM exhibited significantly higher stress intensity and diverse stress types, resulting in stress or damage to the organism. The toxic mechanisms of ICM are concentration/property-dependent and relevant to the cellular structure and defense systems in prokaryotes and eukaryotes. In particular, the toxicity of ionic ICM is higher than that of non-ionic ICM, and eukaryotes are more susceptible than prokaryotes to ICM exposure.

Prevalence, risk factors, and management of dementia and mild cognitive impairment in adults aged 60 years or older in China: a cross-sectional study.

BACKGROUND: China has a large population of older people, but has not yet undertaken a comprehensive study on the prevalence, risk factors, and management of both dementia and mild cognitive impairment (MCI). METHODS: For this national cross-sectional study, 46 011 adults aged 60 years or older were recruited between March 10, 2015, and Dec 26, 2018, using a multistage, stratified, cluster-sampling method, which considered geographical region, degree of urbanisation, economic development status, and sex and age distribution. 96 sites were randomly selected in 12 provinces and municipalities representative of all socioeconomic and geographical regions in China. Participants were interviewed to obtain data on sociodemographic characteristics, lifestyle, medical history, current medications, and family history, and then completed a neuropsychological testing battery administered by a psychological evaluator. The prevalence of dementia (Alzheimer's disease, vascular dementia, and other dementias) and MCI were calculated and the risk factors for different groups were examined using multivariable-adjusted analyses. FINDINGS: Overall age-adjusted and sex-adjusted prevalence was estimated to be 6·0% (95% CI 5·8-6·3) for dementia, 3·9% (3·8-4·1) for Alzheimer's disease, 1·6% (1·5-1·7) for vascular dementia, and 0·5% (0·5-0·6) for other dementias. We estimated that 15·07 million (95% CI 14·53-15·62) people aged 60 years or older in China have dementia: 9·83 million (9·39-10·29) with Alzheimer's disease, 3·92 million (3·64-4·22) with vascular dementia, and 1·32 million (1·16-1·50) with other dementias. Overall MCI prevalence was estimated to be 15·5% (15·2-15·9), representing 38·77 million (37·95-39·62) people in China. Dementia and MCI shared similar risk factors including old age (dementia: odds ratios ranging from 2·69 [95% CI 2·43-2·98] to 6·60 [5·24-8·32]; MCI: from 1·89 [1·77-2·00] to 4·70 [3·77-5·87]); female sex (dementia: 1·43 [1·31-1·56]; MCI: 1·51 [1·43-1·59]); parental history of dementia (dementia: 7·20 [5·68-9·12]; MCI: 1·91 [1·48-2·46]); rural residence (dementia: 1·16 [1·06-1·27]; MCI: 1·45 [1·38-1·54]); fewer years of education (dementia: from 1·17 [1·06-1·29] to 1·55 [1·38-1·73]; MCI: from 1·48 [1·39-1·58] to 3·48 [3·25-3·73]); being widowed, divorced, or living alone (dementia: from 2·59 [2·30-2·90] to 2·66 [2·29-3·10]; MCI: from 1·58 [1·44-1·73] to 1·74 [1·56-1·95]); smoking (dementia: 1·85 [1·67-2·04]; MCI: 1·27 [1·19-1·36]), hypertension (dementia: 1·86 [1·70-2·03]; MCI: 1·62 [1·54-1·71] for MCI), hyperlipidaemia (dementia: 1·87 [1·71-2·05]; MCI: 1·29 [1·21-1·37]), diabetes (dementia: 2·14 [1·96-2·34]; MCI: 1·44 [1·35-1·53]), heart disease (dementia: 1·98 [1·73-2·26]; MCI: 1·17 [1·06-1·30]), and cerebrovascular disease (dementia: 5·44 [4·95-5·97]; MCI: 1·49 [1·36-1·62]). Nine of these risk factors are modifiable. INTERPRETATION: Dementia and MCI are highly prevalent in China and share similar risk factors. A prevention strategy should be developed to target the identified risk factors in the MCI population to thwart or slow down disease progression. It is also crucial to optimise the management of dementia and MCI as an important part of China's public health system. FUNDING: Key Project of the National Natural Science Foundation of China, National Key Scientific Instrument and Equipment Development Project, Mission Program of Beijing Municipal Administration of Hospitals, Beijing Scholars Program, Beijing Brain Initiative from Beijing Municipal Science & Technology Commission, Project for Outstanding Doctor with Combined Ability of Western and Chinese Medicine, and Beijing Municipal Commission of Health and Family Planning.

The Effect of Chronic Cerebral Hypoperfusion on Blood-Brain Barrier Permeability in a Transgenic Alzheimer's Disease Mouse Model (PS1V97L).

The blood-brain barrier (BBB) can restrict the therapeutic effects of Alzheimer's disease (AD) medications. While a large number of AD drug treatment trials targeting BBB dynamics have emerged, most have failed due to insufficient permeability. Furthermore, a subset of AD cases, which also feature chronic hypoperfusion are complicated by BBB deficits. We used a mouse model of AD with chronic hypoperfusion-transgenic mice (PS1V97L) with right common carotid artery ligation. In this model, we assessed how chronic cerebral hypoperfusion changed the pathophysiological processes that increase BBB permeability. Compared with control mice, AD mice with chronic hypoperfusion revealed significantly upregulated expression of the receptor for advanced glycation end products (RAGE) on the BBB. Upregulated RAGE caused increased accumulation of amyloid-ß (Aß) in the brain in these mice. Upregulation of RAGE (or binding to Aß) can promote activation of the NF-κB pathway and enhance oxidative stress and increase the release of pro-inflammatory factors. These factors promoted the reduction of tight junction proteins between the endothelial cells in the BBB and increased its permeability. These findings suggest that the transporter RAGE dysregulation on the BBB initiates a series of pathophysiological processes which lead to increased BBB permeability. Taken together, we have shown that chronic hypoperfusion can serve to enhance and aggravate the BBB impairment in AD.

Sulforaphane Inhibits the Generation of Amyloid-ß Oligomer and Promotes Spatial Learning and Memory in Alzheimer's Disease (PS1V97L) Transgenic Mice.

Abnormal amyloid-ß (Aß) aggregates are a striking feature of Alzheimer's disease (AD), and Aß oligomers have been proven to be crucial in the pathology of AD. Any intervention targeting the generation or aggregation of Aß can be expected to be useful in AD treatment. Oxidative stress and inflammation are common pathological changes in AD that are involved in the generation and aggregation of Aß. In the present study, 6-month-old PS1V97L transgenic (Tg) mice were treated with sulforaphane, an antioxidant, for 4 months, and this treatment significantly inhibited the generation and aggregation of Aß. Sulforaphane also alleviated several downstream pathological changes that including tau hyperphosphorylation, oxidative stress, and neuroinflammation. Most importantly, the cognition of the sulforaphane-treated PS1V97L Tg mice remained normal compared to that of wild-type mice at 10 months of age, when dementia typically emerges in PS1V97L Tg mice. Pretreating cultured cortical neurons with sulforaphane also protected against neuronal injury caused by Aß oligomers in vitro. These findings suggest that sulforaphane may be a potential compound that can inhibit Aß oligomer production in AD.

The Effect of Chronic Cerebral Hypoperfusion on Amyloid-ß Metabolism in a Transgenic Mouse Model of Alzheimer's Disease (PS1V97L).

Alzheimer's disease (AD) and cerebrovascular disease often coexist. However, it is difficult to determine how chronic cerebral hypoperfusion affects the metabolism of amyloid-ß peptides (Aß) in a living patient with AD. Thus, we developed an animal model of this condition, using transgenic mice (PS1V97L) and right common carotid artery ligation to create chronic cerebral hypoperfusion. The metabolic processes associated with amyloid-ß peptide (Aß) were observed and evaluated in this PS1V97L plus hypoperfusion model. Compared with control mice, the model revealed significantly upregulated expression of Aß (including Aß oligomers), with decreased α-secretase activity and expression and increased ß-secretase activity and expression. Furthermore, the model revealed increased mRNA and protein expression of the receptor for advanced glycation end products (RAGE) and decreased mRNA and protein expression of low-density lipoprotein receptor-related protein 1 (LRP-1); both these are Aß transporters. Moreover, the model revealed decreased activity and expression of neprilysin, which is a peripheral Aß degrading enzyme. These findings suggest that hypoperfusion may magnify the effect of AD on Aß metabolism by aggravating its abnormal production, transport, and clearance.