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In recent years, the study of microplastics (MPs) and nanoplastics (NPs) and their effects on human health has gained significant attention. The impacts of NPs on lipid metabolism and the specific mechanisms involved remain poorly understood. To address this, we utilized high-throughput sequencing and molecular biology techniques to investigate how endoplasmic reticulum (ER) stress might affect hepatic lipid metabolism in the presence of polystyrene nanoplastics (PS-NPs). Our findings suggest that PS-NPs activate the PERK-ATF4 signaling pathway, which in turn upregulates the expression of genes related to lipid synthesis via the ATF4-PPARγ/SREBP-1 pathway. This activation leads to an abnormal accumulation of lipid droplets in the liver. 4-PBA, a known ER stress inhibitor, was found to mitigate the PS-NPs-induced lipid metabolism disorder. These results demonstrate the hepatotoxic effects of PS-NPs and clarify the mechanisms of abnormal lipid metabolism induced by PS-NPs.

Foodborne carbon dots (CDs), an emerging food nanocontaminant, are an increasing risk factor for metabolic toxicity in mammals. Here, we report that chronic CD exposure induced glucose metabolism disorders via disruption of the gut–liver axis in mice. 16s rRNA analysis demonstrated that CD exposure decreased the abundance of beneficial bacteria (Bacteroides, Coprococcus, and S24-7) and increased the abundance of harmful bacteria (Proteobacteria, Oscillospira, Desulfovibrionaceae, and Ruminococcaceae), as well as increased the Firmicutes/Bacteroidetes ratio. Mechanistically, the increased pro-inflammatory bacteria release the endotoxin lipopolysaccharide, which induces an intestinal inflammation and disruption of the intestinal mucus layer, activating systemic inflammation and inducing hepatic insulin resistance in mice via the TLR4/NFκB/MAPK signaling pathway. Furthermore, these changes were almost completely reversed by probiotics. Fecal microbiota transplantation from CD-exposed mice induced glucose intolerance, damaged liver function, intestinal mucus layer injury, hepatic inflammation, and insulin resistance in the recipient mice. However, microbiota-depleted mice exposed to CDs had normal levels of these biomarkers consistent with microbiota-depleted control mice, which revealed that gut microbiota dysbiosis contributes to CD-induced inflammation-mediated insulin resistance. Together, our findings revealed that gut microbiota dysbiosis contributes to CD-induced inflammation-mediated insulin resistance and attempted to elucidate the specific underlying mechanism. Furthermore, we emphasized the importance of assessing the hazards associated with foodborne CDs.

C16H16FN3O, orthorhombic, Pbca(no. 61), a= 12.5936(10) Å, b= 7.7308(9) Å, c= 29.568(3) Å, V= 2878.7(5) Å3, Z= 8, Rgt(F) = 0.0872, wRref(F2) = 0.1893, T = 293 K.

C14H22N2O5, orthorhombic, P212121(no. 19), a= 8.0704(12) Å, b= 9.0136(13) Å, c= 20.596(3) Å, V= 1498.2(4) Å3, Z= 4, Rgt(F) = 0.0429, wRref(F2) = 0.1112, T = 296 K.

In this study, the fractional variational iteration method using He’s polynomials is employed for constructing semi-analytical solutions of the fractional-in-time generalized nonlinear Schrödinger equation involving Jumarie’s modified Riemann–Liouville derivative. As a result, we obtain the solutions of the original problems in the forms of convergent series that are calculated easily. Our calculation results indicate that the method is quite efficient and convenient for these problems.

C17H14Cl2N2O2, monoclinic, P21/n(no. 14), a= 8.4863(17) Å, b= 12.654(2) Å, c= 15.088(3) Å, β= 103.612(5)°, V= 1574.8(5) Å3, Z= 4, Rgt(F) = 0.0423, wRref(F2) = 0.1472, T = 205 K.

Epilepsy is one of chronic neurological disorders that affects 0.5–1.0% of the world’s population during their lifetime. There is a still significant need to develop novel anticonvulsant drugs that possess superior efficacy, broad spectrum of activities and good safety profile.

Background: Epilepsy is one of chronic neurological disorders that affects 0.5–1.0% of the world’s population during their lifetime. There is a still significant need to develop novel anticonvulsant drugs that possess superior efficacy, broad spectrum of activities and good safety profile. Methods: a-Asaronol and two current antiseizure drugs (a-asarone and carbamazepine (CBZ)) were assessed by in vivoanticonvulsant screening with the three most employed standard animal seizure models, including maximal electroshock seizure (MES), subcutaneous injection-pentylenetetrazole (PTZ)-induced seizures and 3-mercaptopropionic acid (3-MP)-induced seizures in mice. Considering drug safety evaluation, acute neurotoxicity was assessed with minimal motor impairment screening determined in the rotarod test, and acute toxicity was also detected in mice. Results: In our results, a-asaronol displayed a broad spectrum of anticonvulsant activity (ACA) and showed better protective indexes (PI = 11.11 in MES, PI = 8.68 in PTZ) and lower acute toxicity (LD50= 2940 mg/kg) than its metabolic parent compound (a-asarone). Additionally, a-asaronol displayed a prominent anticonvulsant profile with ED50values of 62.02 mg/kg in the MES and 79.45 mg/kg in the sc-PTZ screen as compared with stiripentol of ED50of 240 mg/kg and 115 mg/kg in the relevant test, respectively. Conclusion: The results of the present study revealed a-asaronol can be developed as a novel molecular in the search for safer and efficient anticonvulsants having neuroprotective effects as well as low toxicity. Meanwhile, the results also suggested that a-asaronol has great potential to develop into another new aromatic allylic alcohols type anticonvulsant drug for add-on therapy of Dravet’s syndrome.

The RPA complex can integrate multiple stress signals into diverse responses by activating distinct DNA repair pathways. However, it remains unclear how RPA1 elects to activate a specific repair pathway during different types of DNA damage. Here, we report that PCAF/GCN5-mediated K163 acetylation of RPA1 is crucial for nucleotide excision repair (NER) but is dispensable for other DNA repair pathways. Mechanistically, we demonstrate that the acetylation of RPA1 is critical for the steady accumulation of XPA at damaged DNA sites and preferentially activates the NER pathway. DNA-PK phosphorylates and activates PCAF upon UV damage and consequently promotes the acetylation of RPA1. Moreover, the acetylation of RPA1 is tightly regulated by HDAC6 and SIRT1. Together, our results demonstrate that the K163 acetylation of RPA1 plays a key role in the repair of UV-induced DNA damage and reveal how the specific RPA1 modification modulates the choice of distinct DNA repair pathways.

Background. Due to its high morbidity and prevalence, the potential relationships of depression/anxiety symptoms in neck pain (NP) are not well demonstrated. Objectives. This study aimed to conduct a comprehensive estimation of controlled trials of psychological problems and to test hypotheses concerning whether NP was statistically relative to anxiety/depression symptoms. Methods. Chinese literature databases such as the China National Knowledge Infrastructure (CNKI), VIP Information (VIP), Chinese Biomedicine (CBM), and Wanfang Data (WANFANG) were scientifically searched for reports published until February 5, 2018. Controlled trials incorporating NP patients with anxiety/depression versus healthy people were contained. Two researchers screened each article and extracted data, respectively, and blinded to the findings of each other. Meta-analysis was conducted by the Cochrane Collaboration’s RevMan 5.3 and Stata 14.0 (Stata Corp LP, USA) software. Results. We identified 13 eligible studies involving 2339 patients and 3290 healthy people. Compared with healthy control participants, the findings indicated that depression/anxiety symptoms were more common or severe in NP patients (respectively, SMD = 0.89; 95% CI = (0.58, 1.20); P<0.01 and SMD = 0.92; 95% CI = (0.65, 1.20); and P<0.01), results from the pooled data demonstrated no statistical significance between depression/anxiety symptoms and gender in NP patients (resp., SMD = 0.16; 95% CI = (−0.18, 0.51); P=0.35 and SMD = −0.08; 95% CI = (−0.42, 0.27); and P=0.67), and the combined data of the incidence of depression or anxiety symptoms revealed significant difference between NP patients and healthy persons (resp., RR = 4.81; 95% CI = (3.30, 7.01); P<0.01 and RR = 3.29; 95% CI = (2.16, 5.00); and P<0.01). In addition, we did not find articles that met the inclusion criteria, which compared NP patients with other physical illnesses in terms of anxiety/depression symptoms. Conclusions. This meta-analysis suggests that anxiety/depression symptoms are associated with high morbidity in NP patients. We consider these reports support the viewpoint that nonspecific mechanisms mediate mental disturbances in NP. This study may have clinical value for NP, offering an underlying target for the prevention and treatment of anxiety/depression.