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The liver toxicity of alkylphenols (APs) has been demonstrated in animal studies. However, relevant epidemiological evidence is still lacking in humans, especially during pregnancy. We obtained the levels of biochemical indicators of liver function in early (<13 weeks, mean gestation=9.80±1.96 weeks) and late (≥32 weeks, mean gestation = 37.23±2.45 weeks) pregnancies from 219 pregnant women in the Guangxi Zhuang birth cohort from 2015–2017. We also examined the serum levels of APs in these pregnant women in early pregnancy. The present study aimed to investigate the correlations between the exposure of pregnant women to APs and their serum liver function indices. The results of the generalized linear model (GLM) in this study revealed that nonylphenol (NP) was positively correlated with total bilirubin (TBIL) (P=0.04) in early pregnancy, and 4-n-nonylphenol (4-N-NP) was negatively correlated with glutamyl transferase (GGT) (P=0.012). In late pregnancy, NP was positively associated with TBIL (P=0.002), and 4-tert-octylphenol (4-T-OP) was positively correlated with alanine aminotransferase (ALT) (P=0.02). Restricted cubic spline (RCS) results revealed dose response relationships between NP and TBIL (Poverall=0.011) and between 4-N-NP and GGT (Poverall=0.007) in early pregnancy. In late pregnancy, there were dose response relationships between NP and TBIL (Poverall=0.001) and between 4-T-OP and ALT (Poverall=0.033). There was also a dose response relationship between NP volume and GGT with an inverted 'U' shape (Poverall=0.041, Pnonlinear=0.012). Bayesian kernel machine regression modeling (BKMR) revealed that TBIL increased significantly (P<0.05) with increasing levels of coexposure to APs in both early and late pregnancy. Overall, exposure to APs during pregnancy affects maternal liver function to varying degrees. The present study provides new epidemiological evidence that exposure to alkylphenols in pregnant women interferes with liver function. • The first study to link APs exposure during pregnancy to maternal liver function. • Different APs affect liver function variably during early and late pregnancy. • BKMR analysis shows significant TBIL increase with APs coexposure in pregnancy. [ABSTRACT FROM AUTHOR]

We have rationally designed and successfully synthesized FeOOH nanosheet arrays supported on alkali-treated nickel foam. The FeOOH NSAs/ATNF material showed superior catalytic performances for OER in charge transfer, mass transport and reaction kinetics than FeOOH powder. The adverse effects caused by global climate warming continue to be a great impetus to develop electrocatalytic water splitting technology for hydrogen source production. However, there is an urgent necessity but it is still a significant challenge to explore electrocatalysts with excellent performance, low cost, and environmental benignity for expediting the oxygen evolution reaction (OER) owing to the sluggish reaction kinetics. Fe-based materials, especially FeOOH, have great potential as OER electrocatalysts but suffers from poor electrical conductivity. Herein, we rationally designed and successfully synthesized FeOOH nanosheet arrays supported on alkali-treated nickel foam (FeOOH NSAs/ATNF) and applied it as an electrocatalyst toward OER. The FeOOH NSAs/ATNF catalyst exhibited outstanding performance with small overpotential, fast kinetics and superior stability in alkaline medium. Our research opens up a facile and effective approach to develop cost-effective and high-performance electrocatalysts for energy conversion, especially for these Fe-based materials with poor electrical conductivity. [ABSTRACT FROM AUTHOR]

Dibutyl phthalate (DBP), used as a plasticizer, is of wide concern as an environmental pollutant since it has certain immunotoxicity. Although there is growing evidence supporting a link between DBP exposure and allergic airway inflammation, there is less information concerned with whether the ferroptosis pathway is involved in DBP-aggravated allergic asthma in ovalbumin (OVA)-sensitized mice. This study aimed to investigate the role and underlying mechanisms of ferroptosis in DBP-exposed allergic asthmatic mice. Balb/c mice were orally exposed to 40 mg/kg−1 DBP for 28 days, followed by sensitization with OVA and seven consecutive challenges with nebulized OVA. We analyzed airway hyperresponsiveness (AHR), immunoglobulins, inflammation and pulmonary histopathology, to investigate whether DBP exacerbates allergic asthma in OVA-induced mice. We also measured the biomarkers of ferroptosis (Fe2+, GPX4, PTGS2), proteins related to the ferroptosis pathway (VEGF, IL-33, HMGB1, SLC7A11, ALOX15, PEBP1), and indices of lipid peroxidation (ROS, Lipid ROS, GSH, MDA, 4-HNE), to explore the role of ferroptosis in DBP+OVA mice. Finally, we used ferrostatin-1 (Fer-1) as an antagonist against the harmful effects of DBP. The results showed that, DBP+OVA mice had a significant increase in AHR, airway wall remodeling and airway inflammation. Further, we showed that DBP aggravated allergic asthma via ferroptosis and lipid peroxidation, and that Fer-1 inhibited ferroptosis and alleviated the pulmonary toxicity of DBP. These results suggest that ferroptosis participates in the exacerbation of allergic asthma resulting from oral exposure to DBP, highlighting a novel pathway for the connection between DBP and allergic asthma. [Display omitted] • Oral exposure to DBP exacerbates allergic asthma in OVA- sensitized mice. • Ferroptosis participates in DBP-aggravated allergic asthma via lipid peroxidation. • Ferrostatin-1 inhibits ferroptosis and alleviates the pulmonary toxicity of DBP. [ABSTRACT FROM AUTHOR]

Epidemiological studies have demonstrated that particulate matter (PM) can induce or exacerbate hypertension. High relative humidity has been associated with elevated blood pressure in certain regions. However, the coupling effect of humidity and PM on elevated blood pressure and the underlying mechanisms remain unknown. Herein, we aimed to explore the effects of exposure to PM and/or high relative humidity on hypertension, as well as elucidate underlying mechanisms. Male C57/BL6 mice were intraperitoneally administered NG-nitro- L -arginine methyl ester (L -NAME) to establish a hypertensive mouse model. The hypertensive mice were exposed to PM (0.15 mg/kg/day) and/or different relative humidities (45/90%) for eight weeks. Histopathological changes, systolic blood pressure (SBP), endothelial-derived contracting factors (thromboxane B 2 [TXB 2 ], Prostaglandin F2α [PGF 2α ], endothelin-1 [ET-1], and angiotensin II [Ang II]), and relaxing factors (prostaglandin I 2 [PGI 2 ] and nitric oxide [NO]) were measured to assess the effects of PM exposure and humidity on hypertension in mice. Levels of transient receptor potential vanilloid 4 (TRPV4), cytosolic phospholipase A 2 (cPLA 2), and cyclooxygenase 2 (COX2) were measured to explore their potential mechanisms. Herein, exposure to 90% relative humidity or PM alone had a slight but insignificant effect on hypertension. However, pathological changes and elevated blood pressure were markedly exacerbated following exposure to PM and 90% relative humidity. Levels of PGF 2α , TXB 2 , and ET-1 were significantly increased, whereas the PGI 2 level was substantially decreased. HC-067047-mediated blockade of TRPV4 suppressed TRPV4, cPLA 2 , and COX2 expression and effectively alleviated the increased blood pressure induced by exposure to PM and 90% relative humidity. These results indicate that 90% relative humidity and PM can activate the TRPV4-cPLA 2 -COX2 ion channel in the aorta, altering the endothelial-derived contracting and relaxing factors and enhancing blood pressure in hypertensive mice. [Display omitted] • Exposure to PM and high relative humidity exacerbate systolic blood pressure of hypertensive mice. • Exposure to PM and high relative humidity aggravate the activation of TRPV4-cPLA2-COX2 pathway. • Blocking TPRV4 can modify the systolic blood pressure and endothelial dysfunction. [ABSTRACT FROM AUTHOR]

In respiratory diseases, the induction of allergic asthma is one of the hottest issues of international concern. The adjuvant effect of air pollutants including nanoparticles (NPs) has be pointed out to facilitate the occurrence and development of allergic asthma. This work studied the development of allergic asthma upon exposures of carbon black nanoparticles (CB NPs, 30–50 nm) and/or high environmental humidity (90% relative humidity). The mechanisms involved were investigated from perspectives of the activation of oxidative stress and transient receptor potential vanilloid 1 (TRPV1) pathways and the alteration in intestinal microbiota. Both high humidity and CB NPs aggravated the airway hyperreactivity, remodeling, and inflammation in Balb/c mice sensitized by ovalbumin. The co-exposure of these two risk factors exhibited adjuvant effect on the development of asthma likely through activating oxidative stress pathway and TRPV1 pathway and then facilitating type I hypersensitivity. Additionally, exposures of high humidity and/or CB NPs reduced the richness of intestinal microbes, altered microbial community composition, and weakened corresponding biological functions, which may interact with the development of asthma. The findings will add new toxicological knowledge to the health risk assessment and management of co-exposures of NPs and other risk factors in the environment. [Display omitted] • Exposures of high humidity and/or CB NPs facilitated the acquired immunity. • Both high humidity and CB NPs aggravated asthma, especially their co-exposure. • Oxidative stress and TRPV1 pathways likely played roles in the combined induction. • Changes of gut microbiota probably participated in the development of asthma. [ABSTRACT FROM AUTHOR]

A weight of evidence (WoE) framework has been applied to assess sediment quality of a typical freshwater lake, Tai Lake in China, where the sediments were contaminated by various chemicals but showed no acute lethality to the benthic invertebrate, Chironomus dilutus . A quantitative scoring method was employed to integrate three lines of evidence (LoE), including adverse effects in life cycle bioassays, biomarker responses, and bioavailability-based chemical analysis. Six biomarkers were determined in C. dilutus after the exposure to the sediments from Tai Lake and provided sensitive indication of sublethal effects at the molecular level. The biomarkers included cytochrome P450, glutathione S -transferase, carboxylesterase, acetylcholinesterase, catalase, and lipid peroxidation. The changes of the biomarkers were summarized for individual sampling sites by computing the integrated biomarker response (IBR) indices. Complementary information was also confirmed by the interrelationship of the LoEs. The IBR indices gained before pupation correlated well with the impairments of emergence of the midges, and altered acetylcholinesterase was corroborated by the detection of chlorpyrifos, an organophosphate pesticide. The relationship between bioavailable toxic units estimated by Tenax extractable concentrations of chemicals in sediment and the observed toxicity in the midges helped to identify the putative toxicity contributors to C. dilutus . Overall, the WoE method clearly distinguished the contaminated sites and ranked them by the level of contamination. Sediment-associated pesticides, particularly γ -hexachlorocyclohexane and chlorpyrifos, were the possible contributors to chronic toxicity to the midges. [ABSTRACT FROM AUTHOR]

Numerous epidemiological studies have recently observed that exposure to traffic-related air pollution (TRAP) is associated with increased risk of various respiratory diseases. Major gaps in knowledge remain regarding the toxicological effects. We examined the toxicological effects of the gasoline exhaust particles (GEP), a paradigm of TRAP, in rats, with an objective to provide the evidence, obtain the biomarkers, and suggest effective intervention measure. We measured the airway hyperresponsiveness (AHR), inflammatory cells in the bronchoalveolar lavage (BAL) fluid, histological changes in the lung tissues, and the biomarkers so as to systematically examine the toxicological effects of GEPs at different dose levels (0.5, 2.5, 5 mg/kg BW). The intervention of vitamin E (VE), a natural antioxidant, on the toxicological effects was investigated. The lung injury caused by GEP exposure was first indicated by the airway hyperresponsiveness (AHR). Compared with the control group, GEP exposure significantly increased the airway resistances and decreased the lung compliance; the higher the dose of GEP, the more serious the lung injury. Lung injury was also revealed by the increase of inflammatory cells, including the lymphocytes and neutrophils, in the BAL fluid. With the increase of GEP dose, histological changes in the lung tissues were further observed: inflammatory cell infiltration increased and alveolar wall thickened. The toxicology of GEP was demonstrated by the increase of the biomarkers of the oxidative stress, the pro-inflammatory cytokines and the apoptosis cytokine. However, administration of VE was found to be effective in restoring airway injury. The toxicological effects of traffic-related air pollution (TRAP) on rat lungs are supported by evidence and biomarkers, and vitamin E intervention is feasible. [Display omitted] • Epidemiological studies observed that traffic-related air pollution increases the risk of respiratory diseases. • We examined the toxicological effects of the gasoline exhaust particles (GEP) on rat lungs. • We found the evidence in the airway hyperresponsiveness, the inflammatory cells in the bronchoalveolar lavage fluid, and histological changes in the lung tissues. • We found the biomarkers of the oxidative stress, the pro-inflammatory cytokines and the apoptosis cytokine. • Vitamin E was found to be effective in reducing the toxicological effects. [ABSTRACT FROM AUTHOR]

Glaucoma is a heterogeneous group of progressive optic neurodegenerative. Although most patients with primary open angle glaucoma (POAG) are stable for many years, certain subgroups of POAG patients could progress over time even with treatment. This study is to identify aqueous humor (AH) biomarkers that may be associated with disease progression in POAG patients. Gene differential expression study of prospectively collected AH from patients with stable or progressive POAG. Metagenomic deep sequencing (MDS) was performed on the aqueous fluid of 20 patients with stable POAG and 20 patients with progressive POAG. Differential gene expression analysis was performed to identify host transcriptome signatures. A total of 21 transcripts were differentially expressed between groups. Differential transcripts identified by MDS. Twenty transcripts were up-regulated and 1 transcript was down-regulated in progressive POAG patients compared to stable patients. Of those, 11 transcripts were eye-related, and 5 transcripts were related to glaucomatous phenotypes (Fibronectin type III domain containing 3B (FNDC3B), Clusterin (CLU), Proprotein convertase subtilisin/kexin type 6 (PCSK6), Cadherin EGF LAG seven-pass G-type receptor 1 (Celsr1), and Rho guanine nucleotide exchange factor 4 (ARHGEF4)). Biomarkers associated with POAG progression can be identified from aqueous fluid. Identification of the biomarkers may improve glaucoma surveillance for progressive POAG. • Identify biomarkers associated with POAG progression from aqueous samples. • Differential transcripts identified by MDS. • Improve glaucoma surveillance for progressive POAG. [ABSTRACT FROM AUTHOR]

Abstract: The accumulation of beta amyloid (Aβ) can cause synaptic impairments, but the characteristics and mechanisms of the synaptic impairment induced by the accumulation of Aβ in Alzheimer''s disease (AD) remain unclear. In identified single neurons in a newly developed Drosophila AD model, in which Aβ accumulates intraneuronally, we found an age-dependent reduction in the synaptic vesicle release probability that was associated with a decrease in the density of presynaptic calcium channel clusters and an increase in the presynaptic and postsynaptic contact length. Moreover, these alterations occurred in the absence of presynaptic bouton loss. In addition, we found that Aβ expression also produced an age-dependent decrease in the amount of Bruchpilot (Brp), which plays an important role in controlling Ca2+ channel clustering and synaptic vesicle release in the presynaptic active zone. Our study indicates that the chronic accumulation of intraneuronal Aβ can induce functional and structural changes in the presynaptic active zone prior to a loss of presynaptic buttons in the same neuron. [Copyright &y& Elsevier]

Abstract: Human peptidoglycan recognition proteins (PGLYRPs) are a novel family of pattern recognition receptors, and also act as anti-bacterial proteins. This study was to explore the toll-like receptor (TLR)-mediated regulation of PGLYRPs in human corneal epithelial cells (HCECs). Fresh human donor corneoscleral tissues were used to prepare cryosections. Primary HCECs, established from limbal explants, were treated with microbial ligands to TLRs 1–9 for 4–48 h, with or without pretreatment of TLR antibodies, NFkB inhibitor, or siRNA transfection. The mRNA of PGLYRPs was evaluated by RT and real-time PCR, and their proteins and NFkB activation were determined by immunostaining and Western blot. The nuclear IRF3 activity was quantified using an ELISA-based TransAM kit. PGLYRP-2, -3 and -4 were found to be expressed by human corneal epithelium while PGLYRP-1 was not detected. In primary HCEC cultures, PGLYRP-3 and -4 were constitutively expressed while PGLYRP-2 was largely inducible. PGLYRP-2 was induced by bacterial components, Pam3CSK4, PGN, flagellin and FSL-1, ligands for TLR2/1, 2, 5 and 2/6, respectively. Interestingly, PGLYRP-2 was strongest stimulated by polyI:C representing viral dsRNA. TLR3 antibody or NFkB inhibitor blocked IRF3 and NFkB p65 activation as well as polyI:C-stimulated PGLYRP-2. RNA interference indicates that the polyI:C-induced PGLYRP-2 was dramatically blocked in the cells transfected with siRNA-TRIF but neither siRNA-MyD88 nor the negative control siRNA-F. These findings suggest that human corneal epithelium may response to viral or bacterial infection by producing PGLYRPs through TLRs, and the induction of PGLYRP-2 by dsRNA was through TLR3-TRIF-IRF3-NFkB signaling pathways. [Copyright &y& Elsevier]

Cooking oil fumes (COF) is one of the primary sources of indoor air pollution in China, which is associated with respiratory diseases such as acute lung injury and lung cancer. However, evidence of COF toxic effect was few. The research was aimed to investigate the toxic effect and the underlying mechanisms induced by COF. The female Wistar rats were randomly divided into several groups, including control group, COF exposure group and VE protection group, and instilled intratracheally with different COF suspensions (0.2, 2, 20 mg/kg) or saline once every 3 days for 30 days. After 24 h of final exposure, all rat were anesthetic euthanasia to draw materials. The alveolar lavage fluid (BALF) was for inflammatory cell count. The lung homogenate was to determine the biochemical indexes such as oxidative stress, apoptosis factors, carcinogenic toxicity and endoplasmic reticulum (ER) stress. The left lung was made for immunohistochemical and histopathological analysis. The results showed that the levels of oxidative stress (ROS), apoptosis factors (NF-κB), carcinogenic toxicity (P53 and 8-OhdG), ER stress (IRE-1α and Caspase-12) in 2 mg/kg and 20 mg/kg COF exposure groups were significantly increased compared with the saline groups. The above pathological changes were improved after vitamin E (VE) supplementation. In addition, the immunohistochemical and histopathological analysis found the same trend. The COF had health risk of heredity and potential carcinogenicity. Besides, COFs can not only induce oxidative stress, but also induce ER stress in lung and airway epithelial cells of female rats through the unfolded protein reaction (UPR) pathway. It revealed that the oxidative stress and ER stress interacted in aggravating lung injury. VE could effectively alleviate the lung injury causing by COF exposure. [Display omitted] ● Indoor air pollution is more harmful to human health than outdoor, especially for women. ● The high concentration (20 mg/kg) of COF is more toxic to rat than COF 2 and COF 0.2. ● COFs can not only induce oxidative stress, but also induce ER stress in lung. ● The COF had health risk of heredity and potential carcinogenicity. ● Vitamin E can effectively prevent COF-induced toxicological effects. [ABSTRACT FROM AUTHOR]

Aging is a major risk factor for various eye diseases, such as cataract, glaucoma, and age-related macular degeneration. Age-related changes are observed in almost all structures of the human eye. Considerable individual variations exist within a group of similarly aged individuals, indicating the need for more informative biomarkers for assessing the aging of the eyes. The morphology of the ocular anterior segment has been reported to vary across age groups, focusing on only a few corneal parameters, such as keratometry and thickness of the cornea, which could not provide accurate estimation of age. Thus, the association between eye aging and the morphology of the anterior segment remains elusive. In this study, we aimed to develop a predictive model of age based on a large number of anterior segment morphology-related features, measured via the high-resolution ocular anterior segment analysis system (Pentacam). This approach allows for an integrated assessment of age-related changes in corneal morphology, and the identification of important morphological features associated with different eye aging patterns. Three machine learning methods (neural networks, Lasso regression and extreme gradient boosting) were employed to build predictive models using 276 anterior segment features of 63,753 participants from 10 ophthalmic centers in 10 different cities of China. The best performing age prediction model achieved a median absolute error of 2.80 years and a mean absolute error of 3.89 years in the validation set. An external cohort of 100 volunteers was used to test the performance of the prediction model. The developed neural network model achieved a median absolute error of 3.03 years and a mean absolute error of 3.40 years in the external cohort. In summary, our study revealed that the anterior segment morphology of the human eye may be an informative and non-invasive indicator of eye aging. This could prompt doctors to focus on age-related medical interventions on ocular health. [ABSTRACT FROM AUTHOR]

The Ni x S/Cu 5 FeS 4 hybrid catalyst with interface structures was developed and as advanced electrocatalysts for HER in the alkaline electrolytes. The interface between Ni x S nanoparticles (NPs) and Cu 5 FeS 4 NPs may lead to electron redistribution and boost the electron transfer ability of Ni 0.2 S/Cu 5 FeS 4 hybrid and effectively improve the catalytic kinetic during the process of alkaline HER electrocatalysis. Bornite (Cu 5 FeS 4) exhibits great potential for the alkaline hydrogen evolution reaction (HER) and few studies have been conducted on its electrocatalytic activity. Herein, we successfully fabricate Ni x S/Cu 5 FeS 4 hybrid catalyst with interface structure between Ni x S nanoparticles (NPs) and Cu 5 FeS 4 NPs. The Ni x S/Cu 5 FeS 4 hybrid catalyst exhibits favorable HER performances in 1.0 M KOH electrolyte and demonstrates smaller overpotential and lower Tafel slope than bare Ni x S NPs and Cu 5 FeS 4 NPs. The remarkable HER performances are attributed to the strongly coupling interface structure between Ni x S NPs and Cu 5 FeS 4 NPs, which leads to synergistic effect optimizing the HER activity and enhancing the charge transfer during catalytic process. This work provides a promising strategy for the construction of Cu 5 FeS 4 -based hybrid catalyst and its application in energy systems. [ABSTRACT FROM AUTHOR]

Liraglutide is a glucagon-like peptide-1 receptor (GLP-1R) agonist and incretin mimetic used for the treatment of Type 2 diabetes mellitus. It has also been shown to have a beneficial role in the cardiovascular system. Here, we investigated the mechanism by which liraglutide promotes angiogenesis using human umbilical vein endothelial cells (HUVECs). HUVECs were treated with various concentrations of liraglutide, and assessed by wound healing assay and tube formation assay as measures of angiogenesis. We found that liraglutide at 10 and 100 nmol/L greatly promoted the angiogenic ability of HUVECs. Next, we examined the JAK2/STAT3 signaling pathway and found that liraglutide treatment led to JAK2/STAT3 activation and significant increase in the angiogenic mediator expressions, including vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and endothelial nitric oxide synthase (eNOS) in HUVECs. Treatment with JAK2 inhibitor, AG490, in HUVECs successfully reduced the observed effects of liraglutide. We conclude that liraglutide promotes the angiogenic ability of HUVECs by activating the JAK2/STAT3 signaling pathway and upregulating its downstream factors, VEGF, bFGF and eNOS. Thus, liraglutide may provide ischemic relief for diabetic patients with cardiovascular diseases in addition to glycemic control. • Liraglutide treatment promotes the angiogenic ability of HUVECs. • Liraglutide treatment activates the JAK2/STAT3 signaling pathway in HUVECs. • Liraglutide treatment enhances the expression of JAK2/STAT3 signaling pathway downstream genes, VEGF, bFGF and eNOS. [ABSTRACT FROM AUTHOR]

Autophagy is a double-edged sword that affects tumor progression by promoting cell survival or death depending on different living contexts. The concrete mechanism by which autophagy modulates the efficacy of radiotherapy for prostate cancer (PC) remains unclear. We exposed RM-1 PC cells to X-ray and explored the role of autophagy in radiation injury. Our results showed increased apoptosis and autophagy levels in RM-1 cells after radiation. Pharmacological inhibition of autophagy by chloroquine significantly mitigated radiation-induced apoptosis, while the enhancement of autophagy by rapamycin aggravated apoptosis. Sirt1, a member of sirtuin family, deacetylates various transcription factors to trigger cell survival in response to radiation injury. We found that radiation led to Sirt1 downregulation, which was reversed by the inhibition of autophagy. On the contrary, enhanced autophagy further diminished protein level of Sirt1. Notably, overexpression of Sirt1 by plasmid significantly alleviated radiation-induced apoptosis, but silenced Sirt1 by siRNA further induced apoptosis, indicating the radioprotective effect of Sirt1 on RM-1 cells. In summary, our findings suggested that autophagy-mediated Sirt1 downregulation might be a promising therapeutic target for PC. • The radiosensitivity of RM-1 prostate cancer cells is dose-dependent. • Autophagy-mediated Sirt1 downregulation causes apoptosis in irradiated RM-1 cells. • There exists an autophagy-Sirt1-apoptosis signaling axis in irradiated RM-1 cells. • Targeting autophagy and Sirt1 may be a potential therapeutic strategy for prostate cancer. [ABSTRACT FROM AUTHOR]

The wheat aphid Sitobion miscanthi is a dominant and destructive pest in agricultural production. Insecticides are the main substances used for effective control of wheat aphids. However, their extensive application has caused severe resistance of wheat aphids to some insecticides; therefore, exploring resistance mechanisms is essential for wheat aphid management. In the present study, CYP6CY2, a new P450 gene, was isolated and overexpressed in the imidacloprid-resistant strain (SM-R) compared to the imidacloprid-susceptible strain (SM-S). The increased sensitivity of S. miscanthi to imidacloprid after knockdown of CYP6CY2 indicates that it could be associated with imidacloprid resistance. Subsequently, the posttranscriptional regulation of CYP6CY2 in the 3′ UTR by miR-3037 was confirmed, and CYP6CY2 participated in imidacloprid resistance. This finding is critical for determining the role of P450 in relation to the resistance of S. miscanthi to imidacloprid. It is of great significance to understand this regulatory mechanism of P450 expression in the resistance of S. miscanthi to neonicotinoids. [Display omitted] • CYP6CY2, a new P450 gene was isolated. • CYP6CY2 was overexpressed in the imidacloprid-resistant strain (SM-R) compared to that in the imidacloprid-susceptible strain (SM-S). • The increased sensitivity to imidacloprid after knockdown of CYP6CY2. • CYP6CY2 in the 3′ UTR regulated by miR-3037 posttranscriptionally. • CYP6CY2 regulated by miR-3037 involved in imidacloprid resistance. [ABSTRACT FROM AUTHOR]

A bifunctional electrocatalyst with peculiarly hierarchical snowflake-like iron doped CoP heterostructures self-assembled on copper foam was synthesised through a facile two-step pathway and employed for efficient OER, HER and overall water splitting. A bifunctional electrocatalyst with peculiarly hierarchical snowflake-like iron-doped CoP heterostructures self-assembled on copper foam (CoFeP/CF) was synthesized via a facile hydrothermal-phosphidation pathway. The excellent electrochemical performance of CoFeP/CF can be attributed to the synergistic effect of cobalt and iron atoms, tuneful interaction between metal atoms and phosphorus, and the large electrochemical active surface area origined from its peculiarly hierarchical snowflake-like heterostructures with high surface roughness. With the small Tafel slope values (of 73.0 mV dec−1 for OER and 90.4 mV dec−1 for HER), CoFeP/CF demands the diminutive overpotentials (of 277.9 mV for OER and 152.6 mV for HER) to desire the current density of 50 mA cm−2 in alkaline electrolyte. Furthermore, CoFeP/CF exhibits outstanding electrochemical performance for the overall water splitting with the cell potential of 1.495 V to attain 10 mA cm−2 in a two-electrode cell. [ABSTRACT FROM AUTHOR]

Abstract Learning disabilities (LDs) in children are a serious global problem. Dibutyl phthalate (DBP), a plasticizer widely used in daily life, has been linked to triggering childhood LDs, however the mechanism underlying this remains unclear. Studies have shown that the ERK 1/2 pathway is closely related to apoptosis of hippocampal neurons. On the basis of these links between LDs, DBP and the ERK 1/2 pathway, we explore whether DBP induces hippocampal neuron apoptosis and increases behavioral disorders in mice via the ERK 1/2 pathway. We looked at oxidative stress, examined the calcium signal, detected the ERK 1/2 pathway and evaluated apoptosis as well as using histological observations, and found that DBP significantly increased oxidative damage and apoptosis in hippocampal neurons via the ERK 1/2 pathway in mice. We also found that pretreatment with the dihydropyridine's (DHP's) Ca2+ antagonist, nimodipine (NMDP), combined with the antioxidant Vitamin E (VE), attenuated ERK 1/2 phosphorylation and DBP-mediated disorders, suggesting that a combined use of VE and NMDP can ameliorate DBP-induced memory deficit and apoptosis via inhibiting the ERK 1/2 pathway. These results indicate that DBP predisposes oxidative damage and apoptosis in hippocampal neurons by activation of the ERK 1/2 pathway, and may be proposed as a possible mechanism underlying LDs in children. Moreover, VE and NMDP may play a certain protective role in the targeted treatment of childhood LDs. Graphical abstract Unlabelled Image Highlights • DBP induces apoptosis of hippocampal neurons via the ERK 1/2 pathway. • DBP activates the ERK 1/2 pathway through ROS accumulation and excessive Ca2+. • VE and NMDP can ameliorate DBP-induced apoptosis by inhibiting the ERK 1/2 pathway. [ABSTRACT FROM AUTHOR]

Decrease of chloride concentration contributes to cardiovascular diseases, however, whether decrease of chloride concentration is involved in platelet activation remains elusive. In the present study, we found that ACI patients had lower serum chloride which would be rescued after Aspirin administration. ADP induced chloride concentration reduction in platelets. Blockade of chloride channel prevented ADP-induced platelet adhesion, activation and aggregation, however, decreasing the extracellular chloride concentration promoted ADP-induced platelet adhesion and activation. Decrease of the extracellular chloride concentration facilitated the inactivation of Src family kinase Lyn, which was not involved in PI3K/Akt phosphorylation. Nevertheless, low chloride concentration promoted the production of platelet cytosol Gαi2 subunit. This subunit prevents AC from converting ATP into cAMP, which therefore, inhibited the phosphorylation of PKA to promote platelet activation. In conclusion, decreased intracellular chloride promotes ADP induced platelet activation through the Gαi2/cAMP/PKA pathway instead of the Lyn/PI3K/Akt signal pathway. [ABSTRACT FROM AUTHOR]

• B. subtilis strain NCD-2 is a biocontrol agent for cotton verticillium wilt. • Fengycin was main antifungal compound against V. dahliae. • Surfactin mainly affected the root colonization of strain NCD-2. • Both fengycin and surfactin contribute to the biocontrol efficiency. Bacillus subtilis strain NCD-2 is a promising biocontrol agent for soil borne plant diseases. A previous study indicated that strain NCD-2 could produce surfactin and fengycin simultaneously. In this study, the exact roles of surfactin and fengycin in strain NCD-2 against cotton verticillium wilt were determined by knockout of the surfactin synthetase gene srfAA and the fengycin synthetase gene fenC. Compared to the wild-type strain NCD-2, the fengycin-deficient mutant ΔFenC decreased the antifungal ability toward Verticillium dahliae , but the surfactin-deficient mutant ΔSrfAA mainly decreased the swarming and biofilm formation abilities of strain NCD-2. Comparatively, the fengycin and surfactin double mutant ΔFenC/SrfAA decreased the antifungal activity and swarming and biofilm formation abilities to more significant levels. The colonization abilities of the wild type strain NCD-2 and its derivative mutants were compared in the cotton rhizosphere. Compared to the wild-type strain NCD-2, ΔSrfAA and ΔFenC/SrfAA exhibited the poorest colonization ability. RT-qPCR results confirmed that knockout of the srfAA and fenC genes decreased the expression of biofilm formation-related genes. The biocontrol abilities of the strains against cotton verticillium wilt were evaluated in a greenhouse. All mutants decreased the biocontrol abilities against cotton verticillium wilt, while ΔFenC/SrfAA showed the poorest biocontrol ability, followed by ΔFenC. Taken together, fengycin was the main antifungal active compound, and surfactin affected root colonization. Both the antifungal ability and root colonization of strain NCD-2 played important roles in suppressing cotton verticillium wilt. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma (RCC) is common renal malignancy within poor prognosis. TGF-β-activated kinase 1 (TAK1) plays vital roles in cell survival, apoptosis-resistance and carcinogenesis through regulating nuclear factor-κB (NF-κB) and other cancer-related pathways. Here we found that TAK1 inhibitors (LYTAK1, 5Z-7-oxozeanol (5Z) and NG-25) suppressed NF-κB activation and RCC cell (786-O and A489 lines) survival. TAK1 inhibitors induced apoptotic cytotoxicity against RCC cells, which was largely inhibited by the broad or specific caspase inhibitors. Further, shRNA-mediated partial depletion of TAK1 reduced 786-O cell viability whiling activating apoptosis. Significantly, TAK1 was over-expressed in human RCC tissues, and its level was correlated with phosphorylated NF-κB. Finally, kinase inhibition or genetic depletion of TAK1 enhanced the activity of vinblastine sulfate (VLB) in RCC cells. Together, these results suggest that TAK1 may be an important oncogene or an effective target for RCC intervention. [ABSTRACT FROM AUTHOR]

• Bacillus subtilis NCD-2 (BS) decreased disease index of CVW, increased cotton yields. • BS did not decreased population of V. dahliae in rhizosphere. • BS increased bacterial and fungal diversities. • BS changed the microbial community structure. • Microbial communities structure was correlated with soil nutrients after BS applicaiton. Bacillus subtilis NCD-2 (BS) shows prominent biological control for cotton verticillium wilt (CVW). However, it is unknown whether the effects on the abundant and rare microbial communities in rhizosphere after application of BS. Therefore, we investigated the effects of BS treatment on the suppression of CVW and the microbial community structure in rhizosphere. BS treatment successfully suppressed CVW, achieving a control effect of 61.60%, and cotton yield increased by 6.07% compared with blank control. Moreover, application of BS resulted in 28.17%, 18.63%, and 5.08% increases in plant fresh weight, dry weight, and number of branches, respectively. However, the populations of Verticillium dahliae in rhizosphere did not decrease by BS treatment. Microbial diversity analysis showed that soil bacterial and fungal diversities were increased under BS treatment. Principal component analyses revealed that BS had significantly effect on the abundant and rare microbial communities. Higher abundances of Acidobacteria, Chloroflexi, and Planctomycetes were observed among abundant bacterial taxa in the BS treatment. Furthermore, the abundances of Arenimonas , Hydrogenophaga, Chaetomium , Aspergillus, Nectria, Psathyrella, Conocybe, and Chrysosporium were also significantly higher than those in blank control. Redundancy analysis indicated that the microbial communities structure in BS treatment were positively related to ammonium nitrogen (NH 4 +-N), inorganic phosphorus (IP), and pH, but negatively to nitrate nitrogen (NO 3 –-N), AK, and organic matter (OM). These research results may offer theoretical bases for comprehensive the mechanism of ecological prevention and control CVW by application of BS. [ABSTRACT FROM AUTHOR]

Abstract: The progressive alterations to the retinal microvasculature in diabetic retinopathy are known to cause vision loss. Chemokines are characterized by their ability to induce cell invasion, adhesion and migration. In this study, we used double siRNA transfection to transiently and selectively decrease the level of the endogenous CXCR4 in human retinal microvascular endothelial cells (HRMECs). The functional consequences of silencing CXCR4 expression in HRMECs were investigated using an endothelial cell migration assay and tubule formation in Matrigel. When CXCR4 expression was decreased with siRNA, HRMECs were less invasive and also resulted in markedly diminished vascular networks on Matrigel as compared to the controls. Additionally, hypoxia and VEGF, the factors affecting microvascular, regulate the expression level of CXCR4 in HRMECs, respectively, which have synergistic, additive effect in the HRMECs. As such, CXCR4 antagonists may become a therapeutic target for the treatment of retinal angiopathies. [Copyright &y& Elsevier]

Abstract: The objective of this study was to establish a spontaneously derived human corneal epithelial cell line from a normal human limbus that retains differentiation potential and proliferative properties under continuous cell culture. After 50 passages of epithelial cells obtained from human limbal tissue a cell line spontaneously emerged. The immortalized cells showed a cobblestone appearance and displayed dense microvilli on their apical cell surface membrane. Colony forming efficiency was 5–6% and population doubling time was 19.6h. In the mRNA level, cytokeratin (CK) 3 and 12 were detected in this cell line. In the protein level, the cells expressed CK3, CK12, CK14, CK19, vimentin, and some other proteins such as F-actin and β-tubulin and β1-integrin. They lacked p63. The immortalized cells had a heteroploid karyotype, but did not exhibit tumorigenic features. When cultured on an air–liquid interface the cells could form stratified multilayer epithelia. In summary, all these results indicated that a new human corneal epithelial cell line was spontaneously established from normal limbal tissue through serial culture. This cell line would be useful for studies of corneal epithelial biology and reconstructive corneal tissue engineering. [Copyright &y& Elsevier]

• Bacillus subtilis NCD-2 decreased incidence of Verticillium wilt, increased yield. • Broccoli residues reduced the DNA copy numbers of Verticillium dahliae in soil. • Broccoli residues decreased fungal community diversity. • Broccoli residues increased the abundance of beneficial microbes. • Broccoli residues return was effective method for controlling potato Verticillium wilt. Potato Verticillium wilt is an economically important disease that significantly decreases tuber yield. Biological control is an effective approach for controlling potato Verticillium wilt. The objective of this study was to evaluate the effects of treatment with Bacillus subtilis NCD-2 (BS), broccoli residues (BR), and combination among them (BB) on potato Verticillium wilt and the soil fungal community structure. Field experiments demonstrated that BS, BR and BB successfully suppressed potato Verticillium wilt, achieving control effects of 32.25%, 48.15%, and 37.85%, respectively. Compared to the untreated control, potato yield increased by 10.38%, 16.82% and 27.12% after the treatments of BS, BR and BB, respectively. Moreover, the BS treatment did not decrease the rhizosphere V. dahliae population, which was significantly decreased by BR (19.08%) and BB (30.46%). Illumina MiSeq analysis showed that soil fungal diversity in the rhizosphere was decreased under BS, BR and BB. Principal component and heatmap analyses showed that BS exerted a similar effect on the fungal community structure to the blank control. However, BR and BB greatly changed the fungal community structure. Moreover, the relative abundance of beneficial microbes such as Chaetomium and Mortierella was higher in the BS and BB soils than in the control. Redundancy analysis (RDA) showed that the fungal community structure under BR and BB was positively correlated with SOM, pH, AP and IP, while the opposite trend was observed under BS. The results suggested that BS seed treatment and BR return could be a useful strategy for potato production in sustainable agriculture; this research may provide a theoretical basis for understanding the mechanism of the ecological control of potato Verticillium wilt. [ABSTRACT FROM AUTHOR]

Obstructive Sleep Apnea (OSA) damages the health of 35% of adult Americans. Disordered sleep results in increased risk of several autoimmune disorders, but the molecular links to autoimmunity are poorly understood. Herein, we identified four cytokines associated with autoimmune disease, whose median serum levels were significantly different for OSA patients receiving airways therapy, from the levels in untreated OSA patients, APRIL (5.2-fold lower, p = 3.5 × 10−11), CD30 (1.6-fold higher, p = 7.7 × 10−5), IFN-Alpha-2 (2.9-fold higher, p = 9.6 × 10−14) and IL-2 (1.9-fold higher, p = 0.0003). Cytokine levels in airways treated patients were similar to the levels in control subjects. t-SNE and UMAP analysis of these high dimensional patient cytokine data identified only two groups, suggesting a similar global response for all four cytokines to airways therapy. Our findings suggest the levels of these four cytokines may be altered by disordered sleep and perhaps by chronic hypoxia. Therapeutic options are discussed. [ABSTRACT FROM AUTHOR]

It has been reported that cholesterol-lowing agents can ameliorate severity of myocarditis. However, the beneficial effect of the agents has been claimed to be independent of cholesterol reduction as there is no significant change in the plasma cholesterol level in myocarditis. In the present study, using experimental autoimmune myocarditis (EAM) rats as an animal model, we demonstrated that EAM induced elevation of cholesterol level and impaired cholesterol efflux capacity in the cardiac tissue. Moreover, serum high-density lipoprotein (HDL) content was reduced and HDL function associated protein Paraoxonase 1 (PON1) activity was decreased. Besides, the major structural protein within HDL, Apolipoprotein A1 (ApoA1) expression in the cardiac tissues was significantly reduced while the level of serum ApoA1 was not significantly altered. Importantly, cholesterol depleting agent methyl-β-cyclodextrin (MβCD) alleviated the development of EAM, as monitored by decreased ratio of heart weight to body weight (HW/BW), decreased infiltration of inflammatory cells and collagen deposition, improved cardiac function, reduced expression of apoptosis-related protein Bax, Fas, FasL and caspase-3 and increased level of anti-apoptotic protein Bcl-2. These results suggest that reduction of cholesterol level in cardiac tissue could suppress EAM-induced cardiac apoptosis through both intrinsic and extrinsic apoptotic pathways. [ABSTRACT FROM AUTHOR]

• Bacillus subtilis strain NCD-2 reduced clubroot disease severity by up to 50%. • Fengycin contributed to cell lysis of P. brassicae resting spore. • Fengycin defective mutant Δ fenC reduced suppression of clubroot. • Fengycin production of B. subtilis NCD-2 is essential for clubroot control. Clubroot, caused by the obligate parasite Plasmodiophora brassicae , is one of the most important diseases of Brassicaceae family. Bacillus spp. that produce lipopeptide antibiotics are often used as biocontrol agents to suppress soilborne diseases. B. subtilis NCD-2 isolated from the cotton rhizosphere has been found to inhibit pathogenic fungi through the production of fengycin-type cyclopeptides. In this study, the biocontrol efficacy of B. subtilis NCD-2 against P. brassicae and the role of fengycin in disease suppression were evaluated on Chinese cabbage in glasshouse. B. subtilis NCD-2 reduced clubroot disease incidence and severity up to 47.7% and 51.6%, respectively, while the fengycin defective mutant Δ fenC and a PhoP/PhoR two-component regulatory system mutant, Δ phoP , were unable to prevent this disease. In vitro, P. brassicae resting spore cells were lysed when treated with standard fengycin and crude fengycin extracts of the wild type B. subtilis NCD-2, but not of its mutant Δ fenC. Moreover, the population dynamics of B. subtilis and P. brassicae was determined using quantitative real-time PCR (qPCR). The results were surprising that the wild type B. subtilis NCD-2 and its mutant Δ fenC colonized at similar rates in the rhizosphere, while levels of P. brassicae DNA in the rhizosphere and root tissue were reduced following B. subtilis NCD-2 treatment, but there was no effect of the mutant Δ fenC. Thus, the production of fengycins in B. subtilis NCD-2 may play a promising role in the suppression of P. brassicae in the rhizosphere and reduction of incidence of clubroot disease in Chinese cabbage. [ABSTRACT FROM AUTHOR]