Search

Psychiatric disorders have great health hazards and the exact pathogeny remains elusive now. We aim to explore the potential interaction effects of mitochondrial function and human behavior on the risks of anxiety and depression.The genome-wide association study (GWAS) data of mitochondrial function (N = 383,476-982,072) were obtained from published studies. Individual level genotype and phenotype data of anxiety, depression and behavioral factors (including drinking, smoking and physical activity) were all from the UK Biobank (N = 84,805-85,164). We first calculated the polygenic risk scores (PRS) of mitochondrial function as the instrumental variables, and then constructed linear regression analyses to systematically explore the potential interaction effects of mitochondrial function and human behavior on anxiety and depression.In total samples, we observed mitochondrial heteroplasmy (MtHz) vs. Drinking (PConsidering all subjects were from UK Biobank, it should be careful to extrapolate our findings to other populations with different genetic background.Our results suggest the significant impacts of mitochondrial function and human behavior interactions on the development of anxiety and depression, providing new clues for clarifying the pathogenesis of anxiety and depression.

Previous studies have suggested a potential association between sleep and telomere length (TL), but its genetic basis remains unclear. In this study, we aimed to explore the genetic correlation and potential causal association between TL and insomnia.The genome-wide association study (GWAS) datasets of TL and insomnia-related traits were used, including insomnia, snoring, daytime dozing and napping. Based on the polygenic risk scores (PRS) of TL, linear regression and linkage disequilibrium score (LDSC) regression were used to preliminarily explore the association between TL and insomnia parameters in the UK Biobank cohort. Then, we investigated the causal association between TL and insomnia by mendelian randomization (MR) analysis and colocalization analysis.In the UK Biobank cohort, the association between TL and insomnia was observed in the female samples (t = 2.968, P = 3.00 × 10Our study found no evidence for causal association between insomnia and TL in individuals of European ancestry. We detected a candidate gene associated with both insomnia and TL, providing novel clues for understanding the roles of this association.

To explore the roles of rare and high-impact variants in sleep duration.Based on the recently released UK Biobank 200k exome dataset, an exome-wide association study was conducted to detect rare variants (minor allele frequency0.01) contributing to sleep duration. Variant annotations were performed by the software tool ANNOVAR. Gene-based burden tests of sleep duration were conducted by the SKAT R-package. After quality control, 137,047 subjects were included in this study. CAUSALdb database was used to explore the related mental traits of identified genes.We detected 730,572 variants with MAF1%, including 3873 frameshift variants, 3977 nonframeshift variants, 449,632 nonsynonymous variants, 1293 startloss variants, 10,254 stopgain variants, 413 stoploss variants, 261,130 synonymous variants, and 3102 variants are annotated as unknown. The burden test of exonic variants detected two exome-wide significant associations for sleep duration including TMIE at 3p21.31 (PThis study reported 2 novel candidate genes for a sleep duration, supporting the roles of rare genetic variants in the regulation of sleep duration.

Aim This study investigates the effects of ginsenoside Rb1 (GsRb1) on methamphetamine (METH)-induced toxicity in SH-SY5Y neuroblastoma cells and METH-induced conditioned place preference (CPP) in adult Sprague-Dawley rats. It also examines whether GsRb1 can regulate these effects through the NR2B/ERK/CREB/BDNF signaling pathways. Methods SH-SY5Y cells were pretreated with GsRb1 (20 μM and 40 μM) for 1 h, followed by METH treatment (2 mM) for 24 h. Rats were treated with METH (2 mg/kg) or saline on alternating days for 10 days to allow CPP to be examined. GsRb1 (5, 10, and 20 mg/kg) was injected intraperitoneally 1 h before METH or saline. Western blot was used to examine the protein expression of NR2B, ERK, P-ERK, CREB, P-CREB, and BDNF in the SH-SY5Y cells and the rats' hippocampus, nucleus accumbens (NAc), and prefrontal cortex (PFC). Results METH dose-dependently reduced the viability of SH-SY5Y cells. Pretreatment of cells with 40 μM of GsRb1 increased cell viability and reduced the expression of METH-induced NR2B, p-ERK, p-CREB and BDNF. GsRb1 also attenuated the expression of METH CPP in a dose-dependent manner in rats. Further, GsRb1 dose-dependently reduced the expression of METH-induced NR2B, p-ERK, p-CREB, and BDNF in the PFC, hippocampus, and NAc of rats. Conclusion GsRb1 regulated METH-induced neurotoxicity in vitro and METH-induced CPP through the NR2B/ERK/CREB/BDNF regulatory pathway. GsRb1 could be a therapeutic target for treating METH-induced neurotoxicity or METH addiction.

The effects of gene-by-environment (G×E) interactions on complex diseases are significant, especially the superimposed effects of multiple environmental factors. However, research on the multi-environments-gene interactions of anxiety, depression, and self-harm is still limited. This study included white individuals (N = 66,041-74,482) from the UK Biobank. We fitted all environmental factors to a single environmental score (ES), and the estimated ES was used to calculate the multiplicative interaction effects between ES and genome-wide SNPs. Heritability was stratified by minor allele frequency (MAF) and linkage disequilibrium (LD). Our research found 10 loci with significant interaction effects, such as rs114830993 (PRICKLE2, P = 2.30 × 10

Multidrug resistance (MDR) is the main challenge faced by cancer chemotherapy. Drug-conjugate offers a promising strategy for breast cancer therapy. In this regard, we developed a DNVM multifunctional drug delivery system by crosslinking doxorubicin (DOX) and vitamin E succinate (VES) with a pH-sensitive hydrazone bond and then encapsulated the DOX-NN-VES prodrug into pH-sensitive hyaluronic acid-2-(octadecyloxy)-1,3-dioxan-5-amine (HOD) micelles. DOX resistant MCF-7/ADR cell were adopted as a model to study the capability and mechanism of MDR reversal. DNVM exhibited much higher cytotoxicity and cell uptake efficiency compared with that of acid-insensitive DOX-VES loaded HOD micelles (DVSM) and DOX loaded HOD micelles (DOXM), indicating the better capacity of DNVM for the reversal of MDR. Moreover, DNVM prevented drug efflux more effectively, inhibited the expression of P-gp, induced excessive production of reactive oxygen species and affected the expression of apoptosis-related proteins. In vivo experiments showed that DNVM significantly inhibited the tumor growth with no obvious changes in the body weight of MCF-7/ADR cells-bearing nude mice. The results suggested that the "double gain" DNVM can synergistically enhance the efficacy of chemotherapeutics for DOX resistant tumor cells and has the potential to overcome tumor MDR. STATEMENT OF SIGNIFICANCE: A dual-functional pH-sensitive doxorubicin - vitamin E succinate prodrug was developed and loaded into tumor microenvironment-sensitive hyaluronic acid-2-(octadecyloxy)-1,3-dioxan-5-amine micelle system (DNVM) for sequencing stimuli-release and overcoming doxorubicin resistance. The "double gain" DNVM can synergistically enhance the efficacy of chemotherapeutics for doxorubicin resistant tumor cells and has the potential to overcome tumor multiple drug resistance.

Adding reinforcement is an effective way to improve the properties of aluminum alloy. Graphene is an ideal reinforcement for the fabrication of aluminum matrix composites (AMCs) due to its excellent comprehensive performances. Friction stir processing (FSP), as a novel processing technology, is an ideal candidate for fabricating graphene-reinforced AMCs with high performances under appropriate conditions. The present paper firstly summarizes the structure-property characteristics of graphene-reinforced AMCs fabricated by FSP. Then the influences of process conditions on the structure-property evolutions of the composites are discussed. It is found that the addition of graphene leads to grain refinement and texture variation of the stir zone during FSP. Besides, mechanical properties, electrical conductivity, thermal conductivity, tribological property and corrosion resistance of the AMCs are considerably affected by the content of graphene and various microstructure evolutions induced by the added graphene. Composite of reinforcement, adding method of graphene, FSP parameters, FSP pass number and FSP path pattern are critical process conditions that determine the microstructures and properties of the AMCs. The present paper not only concludes major findings of the previous researches but also suggests future recommendations for fabrication of graphene-reinforced AMCs through FSP.

Background & Aims Chronic endoplasmic reticulum (ER) stress in the liver has been shown to play a causative role in non-alcoholic fatty liver disease (NAFLD) progression, yet the underlying molecular mechanisms remain to be elucidated. Forkhead box A3 (FOXA3), a member of the FOX family, plays critical roles in metabolic homeostasis, although its possible functions in ER stress and fatty liver progression are unknown. Methods Adenoviral delivery, siRNA delivery, and genetic knockout mice were used to crease FOXA3 gain- or loss-of-function models. Tunicamycin (TM) and a high-fat diet (HFD) were used to induce acute or chronic ER stress in mice. Chromatin immunoprecipiation (ChIP)-seq, luciferase assay, and adenoviral-mediated downstream gene manipulations were performed to reveal the transcriptional axis involved. Key axis protein levels in livers from healthy donors and patients with NAFLD were assessed via immunohistochemical staining. Results FOXA3 transcription is specifically induced by XBP1s upon ER stress. FOXA3 exacerbates the excessive lipid accumulation caused by the acute ER-inducer TM, whereas FOXA3 deficiency in hepatocytes and mice alleviates it. Importantly, FOXA3 deficiency in mice reduced diet-induced chronic ER stress, fatty liver, and insulin resistance. In addition, FOXA3 suppression via siRNA or adeno-associated virus delivery ameliorated the fatty liver phenotype in HFD-fed and db/db mice. Mechanistically, ChIP-Seq analysis revealed that FOXA3 directly regulates Period1 (Per1) transcription, which in turn promotes the expression of lipogenic genes, including Srebp1c, thus enhancing lipid synthesis. Of pathophysiological significance, FOXA3, PER1, and SREBP1c levels were increased in livers of obese mice and patients with NAFLD. Conclusion The present study identified FOXA3 as the bridging molecule that links ER stress and NAFLD progression. Our results highlighted the role of the XBP1s–FOXA3–PER1/Srebp1c transcriptional axis in the development of NAFLD and identified FOXA3 as a potential therapeutic target for fatty liver disease. Lay summary The molecular mechanisms linking endoplasmic reticulum stress to non-alcoholic fatty liver disease (NAFLD) progression remain undefined. Herein, via in vitro and in vivo analysis, we identified Forkhead box A3 (FOXA3) as a key bridging molecule. Of pathophysiological significance, FOXA3 protein levels were increased in livers of obese mice and patients with NAFLD, indicating that FOXA3 could be a potential therapeutic target in fatty liver disease.

Higher cutting speed is always the pursuit of industries as it is one of the most effective methods to improve machining efficiency, which requires a better understanding of deformation and microstructure evolution process during chip formation. In this study, chip formation process is divided into three different sections of pre-loading, loading and unloading to analyze the mechanisms of microstructure evolution sequentially through a coupled finite element and cellular automata approach. The non-uniform distributed fields of strains, strain rates and temperatures induced by different stage during chip formation process are obtained and then transferred as boundary conditions for microstructure evolution. In pre-loading condition, microstructure evolution appears only along shear band with small sizes, which provides more boundaries for activation of DRX mechanisms in following conditions. Final microstructures always show a gradient distribution along shear direction, and secondary shear zone makes the greatest contribution to grain refinement. Average grain sizes and microstructure distribution have shown a good agreement between experimental data and simulation results, which indicates that this sequential simulation approach can perform a better description of those process characteristics of microstructure evolution during a continuous process with complicated boundary conditions.

In order to explore a novel approach to weaken the tool/workpiece interaction during friction stir lap welding of dissimilar materials, Al and Cu plates with 3 mm thickness are successfully friction stir lap welded without tool penetration into the lower hard Cu plate at high rotation speeds. Large-size Al-Cu coexistence zones composed of the composite-like structures and layered structures are formed at the Al-Cu interfaces for 2500 and 3000 rpm, where intermetallic phases Al2Cu, AlCu and Al4Cu9 are identified. Increasing rotation speeds to 3500 and 4000 rpm leads to the formation of thin and uniformly distributed layered structures featured by indiscernible intermetallic compounds at the Al-Cu interfaces, and significant hook-like structures are extended from the lower Cu sheets into the upper Al sheets. All joints fail along the Al-Cu interfaces during tensile shear test. The lap joints fabricated at 2500 and 3000 rpm present higher fracture loads than those produced at 3500 and 4000 rpm, owing to the more sufficient material mixing and the induced larger Al-Cu bonding areas under the pin stirring effects.

MnO2 has the highest potential as a supercapacitor electrode; however, its disadvantage in electronic conductivity hinders its widespread use. This study reports the excellent electrochemical performance of MnMC/NF (MnO2 and ZIF-derived nanoporous carbon on nickel foam) composites. MnMC/NF composites are produced when leaf-like Co-ZIF is annealed on nickel foam, followed by potassium permanganate treatment. When the annealing temperature reaches 700 °C, the maximum specific capacitance of 531 F/g is achieved at 1 A/g (456 F/g at 20 A/g) with a rate capability of 85.5%. MnMC/NF700 has a long cyclic stability, and the capacitance retention was 82% after 5000 cycles. The energy density of an assembled device using MnMC/NF700 composite as positive electrodes can reach 38.8 Wh/kg. This is due to the combined effect of nickel substrate's 3D porous structure and the excellent electronic conductivity of ZIF-derived nanoporous carbon. The unique configuration of MnMC/NF composites may provide a referable design for energy storage systems, including materials that have the highest potential for use as supercapacitor electrodes.

The widespread use of perfluorooctanoic acid (PFOA) has rendered its frequent detection in wastewater. The tolerance and recovery of aerobic granular sludge (AGS) to PFOA were investigated in short-term (Phase I) and long-term (Phase II, operation strategy adjustment: shortening aeration time and prolonging anaerobic and anoxic time). Results showed that in Phase I, the performance of R2 reactor (0.05 mg/L PFOA) was slightly negatively affected, while 0.5 and 2.0 mg/L PFOA in R3 and R4 reactors significantly damaged the key enzyme activities of AGS, leading to deterioration of nutrients removal. TN and TP removal efficiencies decreased correspondingly from 79.3% to 78.3% on day 0-74.7% and 74.1% in R2 and 68.6% and 67.8% in R3 and 56.9% and 57.5% in R4 on day 7, respectively. In Phase Ⅱ, the key enzyme activities of AGS were obviously renewed dependent on operation strategy adjustment and AGS self-regulation. The performance of AGS in R2 (continuously dosing 0.05 mg/L PFOA) and R4 (stopping dosing PFOA) recovered quite good, while the long-term adverse effects of 0.5 mg/L PFOA on AGS in R3 were still more difficult to be alleviated. In end of Phase Ⅱ (69-97days), the average TN and TP removal efficiencies correspondingly reached 83.3% and 82.1% in R1 (control), 80.7% and 79.6% in R2, 76.4% and 74.3% in R3, and 79.0% and 78.3% in R4, respectively. Further analysis revealed that the effect of PFOA on proteins in extracellular polymeric substances (EPS) was greater than that on polysaccharides. Specifically, short-term dosage of PFOA mainly affected loosely bound EPS, while long-term dosage of PFOA affected tightly bound EPS. Although AGS is severely inhibited by short exposure to 2.0 mg/L PFOA (in R4), after the operation strategy adjustment, EPS content decreased, nutrient and oxygen transport channels of AGS were re-established, which contributed to the recovery of AGS.

Passerine birds have been increasingly used as effective sentinels of ecosystem contamination. They can provide direct evidence of the bioavailability and accumulation of heavy metal elements in the environment. In this study, the bioaccumulation of four heavy metals (Cu, Zn, Pb, and Cd) and Ca in different organs and tissues (feathers, internal organs, skeletons, and muscles) of an urban bird, tree sparrow (Passer montanus), collected from a polluted site [Baiyin (BY)] and a relatively unpolluted site [Liujiaxia (LJX)], and their associations were investigated. There were significantly higher and lower concentrations of heavy metals and Ca, respectively, in different organs and tissues of sparrows in BY than those in LJX. However, except for Pb, the heavy metal levels were below the threshold of sublethal effects. Age-dependent variations in metals were quantified, and it was found that adult bird contained higher concentration of different organs and tissue metals, except for feathers, compared with nestlings and juveniles. The tissue distribution of heavy metals in sparrows of different ages and sex was similar in the two study sites, and heavy metal elements were mainly accumulated in the feathers. This study further investigated the correlation between heavy metals in different organs and tissues and found that the correlations between them were strong in nestlings and adults but weak in juveniles. In addition, Pb and Cd in internal organs, skeletons, and muscles of young sparrows can be estimated using feathers, whereas Cu and Zn were found in adult sparrows. Altogether, our results suggest that tree sparrows will serve as valuable biomonitors of environmental heavy metal pollution and will underscore the importance of tissue types in avian ecotoxicology field studies.

Heparosan is a natural precursor of heparin biosynthesis in mammals. It is stable in blood circulation but can be degraded in lysosomes, showing good biocompatibility and long circulation features. So heparosan can be designed as anticancer drug carriers to increase tumor selectivity and improve the therapeutic effect. A novel redox-sensitive heparosan-cystamine-vitamin E succinate (KSV) micelle system was constructed for intracellular delivery of doxorubicin (DOX). Simultaneously, the redox-insensitive heparosan-adipic acid dihydrazide-vitamin E succinate copolymer (KV) was synthesized as control. DOX-loaded micelles (DOX/KSV) with an average particle size of 90–120 nm had good serum stability and redox-triggered depolymerization. In vitro drug release test showed that DOX/KSV micelles presented obvious redox-triggered release behavior compared with DOX/KV. Cytotoxicity and cell uptake were investigated using MGC80-3 tumor cells and COS7 fibroblast-like cells. The cell survival rate of blank micelles was more than 90%, and the cytotoxicity of DOX/KSV in MGC80-3 cells was higher than in COS7 cells, indicating that the carrier has better biocompatibility and less toxicity side effect. The cytotoxicity of DOX/KSV against MGC80-3 cells was significantly greater than that of free DOX and DOX/KV. Furthermore, compared with DOX/KV in MGC80-3 cells, DOX/KSV micelles uptook more anticancer drugs and then released DOX faster into the cell nucleus. The micelles were endocytosed by multiple pathways, but clathrin-mediated endocytosis was the main pathway. Therefore, heparosan polysaccharide could be a potential option as anticancer carrier for enhancing efficacy and mitigating toxicity., Graphical abstract Redox-sensitive amphiphilic KSV copolymer was designed to deliver DOX. After passive targeted and uptaken by tumor cells, DOX was released rapidly into the nucleus in the intracellular reduced environment.Image, graphical abstract

Hole-transport material-free (HTM-free) perovskite solar cells (PSCs) have the advantages of low manufacturing cost and excellent stability, however, the power conversion efficiencies (PCEs) of these PSCs are relatively low due to the high recombination rate at charge transport interface contacts. Herein, a novel bilayer electron-transport scaffold of SiO2/NaYF4:Yb,Er@SiO2 modified TiO2 nanorods was designed to improve the performance of HTM-free PSCs. Facilitated by the 1D nanorods structure of underneath TiO2 scaffold, photogenerated charges can be quickly transported out of perovskite film with reduced recombination, and the NaYF4:Yb,Er@SiO2 insulating capping layer can further inhibit the charge recombination by removing charge shorting pathways caused by the tangle of TiO2 nanorods with carbon back contact. Moreover, NaYF4:Yb,Er can upconvert near-infrared light into visible region that can be directly used by perovskite materials to improve the current density of corresponding PSCs. Our PSCs have an average PCE of 14.01 ± 0.53%. We demonstrated that up-conversion of light at 980 nm was possible but up-conversion made no statistical improvement in performance.

Background Relatively little is known about preoperative anxiety and its associated factors with colorectal cancer, which is one of the most prevalent cancers. We aimed to investigate preoperative anxiety and its associated social, psychological and coping factors based on the disclosure/nondisclosure of cancer diagnosis. Methods A cross-sectional study was conducted in consecutive colorectal cancer inpatients (N = 434), whose anxiety was assessed based on semi-structured interview, demographic-clinical variables, social support, self-esteem and coping styles (acceptance-resignation, confrontation, avoidance). Hierarchical regression analyses were conducted to explore the relationships between social, psychological, coping factors and preoperative anxiety. Results There was no significant difference in preoperative anxiety (χ2 = 1.031, p = .31) between the disclosure and nondisclosure groups. Social, psychological and coping factors together accounted for an additional variance of preoperative anxiety (disclosure: 22%; nondisclosure: 20.8%). Social support (β = −0.17, p = .004), self-esteem (β = −0.22, p = .001) and coping styles (acceptance-resignation: β = 0.32, p Conclusions Coping styles, such as acceptance-resignation and confrontation, could aggravate preoperative anxiety. Avoidance, social support and self-esteem might be helpful in preventing preoperative anxiety. These findings highlight the importance of providing psychological interventions for cancer patients by integrating social support, self-esteem and coping styles when disclosing a cancer diagnosis.

Water inflow is a crucial factor in underground water-sealed storage for both safety and operation costs. Water inflow control measurements have mainly focused on the grouting of the cavern regardless of considering the influence of the access tunnel (i.e. the water flows directly through the fissures connecting the access tunnel and tanks after the access tunnel impoundment). In this study, the water control measurement related to access tunnel was investigated in certain project. First, based on monitoring data before the operational condition (including water inflow, groundwater level, and operating water level), the water inflow variation laws were explored in different construction phases. Then, the cause for abnormal increase in the water inflow after the access tunnel impoundment was explored using cross-correlation analysis and linear regression. Finally, some novel recommendations were provided for avoiding the abnormal increase in water inflow after the access tunnel impoundment: (1) zones with great fracture density or zones of water leakage should be identified through a geological survey and grouted before the access tunnel impoundment; (2) the access tunnel should avoid intersecting the advantage trend of fissures at a large angle to the greatest extent possible, and the layout of the access tunnel could be changed from the “wrap-around” to “direct-type” configuration; (3) smaller cross-section sizes and shorter lengths should be adopted for the access tunnel to retain proper functioning of the access tunnel and reduce the possibility of hydraulic connections between the access tunnel and tanks.

Surface passivation of the electron transport layer in perovskite solar cells has been proven to be one crucial strategy to improve the power conversion efficiency. In this study, we introduce rutile phase titania shell to passivate anatase TiO2 scaffold, forming anatase@rutile mixed-phase TiO2 scaffold in hole-conductor-free carbon based perovskite solar cells. Anatase@rutile mixed phase TiO2 films exhibit higher conductivity, faster charge extraction, lower trap density and suppressed charge recombination at the interface of TiO2/perovskite films in the modified devices as well, achieving a champion power conversion efficiency of 15.21% for carbon based perovskite solar cells. More importantly, benefiting from the stable and better ultraviolet light filtration properties of rutile phase TiO2, our devices exhibit excellent stability maintaining 92% of their initial efficiency after 200 days storage in ambient air, highlighting their merits as a potential competitor for future industrial photovoltaics.

Polybrominated diphenyl ethers (PBDEs) are present in biosolids and other solid wastes, as well as being detected in landfill leachates. As sand-bentonite mixtures are extensively used as basal liner materials for landfills, a sand-bentonite mixture was investigated by swelling tests and leaching column tests to determine whether it can effectively contain and/or immobilize PBDEs in landfill leachate. Leaching column tests were conducted with permeants consisting of biosolids’ leachates diluted to 50% by volume and spiked with 50 μg/mL of a pentaBDE mixture solution. The results showed that the sand-bentonite retained up to 45–66% of the total PBDEs in the permeant; however, the concentration of PBDEs in the effluent increased continuously and reached a significant level during a 3-week period. PBDEs probably sorbed onto both fine and ultra-fine organic particles. During leaching, a compacted sand-bentonite admix could stop fine particles from passing, but at the same time, ultra-fine organic particles carried PBDEs through the barrier materials. The hydraulic conductivity, k, of the sand-bentonite was negatively affected by shrinkage of the clay interlayer caused by the permeant hydrophobicity. However, the hydraulic conductivity changed only to a limited extent, remaining at a magnitude of 10−9 cm/s, probably because the PBDE concentrations were low. Therefore, caution is needed when sand-bentonite is applied to landfill liners as a barrier for PBDEs.

Microplastics are widely detected in sewage and sludge in wastewater treatment plants and can thereby influence biological processes. In this study, the overall impacts of polyethylene microplastics (PE MPs) and their toxicity mechanisms on aerobic granular sludge (AGS) were investigated. Particle structure, settling properties, particle size distribution, and extracellular polymeric substance characteristics of AGS were significantly affected by PE MPs with concentrations of 20 and 200 n/L. Increased relative contents of reactive oxygen species (ROS) (146.34% and 191.43%) and lactate dehydrogenase (LDH) (185.71% and 316.67%) under PE MPs (20 and 200 n/L) exposure resulted in disruption of cellular structure. The activities of enzymes related to denitrification and phosphorus removal were greatly decreased, while ammonia monooxygenase (AMO) was stable, supporting the high efficiency removal of ammonia nitrogen. High-throughput sequencing demonstrated that the relative abundance of nitrifying and denitrifying bacteria (Nitrospira, Thermomonas, Flavobacterium), and PAOs (Comamonas and Rhodocyclus) were significantly reduced from 4.47%, 3.57%, 2.02%, 9.38%, and 5.45%-2.95%, 2.88%, 1.77%, 8.01%, and 4.86% as the concentration of PE MPs increased from 0 to 200 n/L, respectively. Those findings were consistent with the deterioration in decontamination capability.

Methamphetamine (METH) is a psychostimulant that is abused throughout the world. METH is a highly addictive drug commonly used by persons living with HIV, and its use can result in cognitive impairment and memory deficits. METH and human immunodeficiency virus-1 transactivator of transcription (HIV-1Tat) have toxic and synergistic effects on the nervous system; however, the mechanism of their synergistic effects has not been clarified. We used BV2 cells, primary microglia, Nrf2-KO C57BL/6J mice, and autopsied brain tissues of METH-abusing, HIV infection, and METH-abusing individuals comorbid with HIV to explore the regulatory role of Nrf2/NQO1/HO-1 signal pathway on microglia autophagy. Our results showed that microglia were significantly activated by METH and HIV-1Tat protein. METH and HIV-1Tat protein combination significantly increase the autophagy-related proteins (LC3-II, Beclin-1, ATG5, and ATG7) expression in microglia and striatum of C57BL/6J mice. After silencing or knocking out the Nrf2 gene, the expression levels of autophagy-related proteins were significantly increased. In human brain tissue, microglia were activated, Nrf2, LC3-II, and Beclin-1 expression levels were raised, and the p62 expression level was decreased. Our results suggested that METH and HIV or HIV-1Tat synergistically affect autophagy. And the Nrf2 pathway plays a vital role in regulating the synergistic induction of microglial autophagy by METH and HIV-1Tat protein. This study may provide a theoretical basis and new ideas for effective targets for pharmacological intervention in HIV-infected patients with drug abuse.

Hyperthyroidism has been identified as a risk factor for cognitive disorders. The hippocampus is a key brain region associated with cognitive function, among which excitatory synapse transmission plays an important role in the process of learning and memory. However, the mechanism by which hyperthyroidism leads to cognitive dysfunction through a synaptic mechanism remains unknown. We investigated the synaptic mechanisms in the effects of hyperthyroidism in an animal model that involved repeated injection of triiodothyronine (T3). These mice displayed impaired learning and memory in the Novel object recognition test, Y-maze test, and Morris Water Maze test, as well as elevated anxiety in the elevated plus maze. Mature dendritic spines in the hippocampal CA1 region of hyperthyroid mice were significantly decreased, accompanied by decreased level of AMPA- and NMDA-type glutamate receptors in the hippocampus. In primary cultured hippocampal neurons, levels of AMPA- and NMDA-type glutamate receptors also decreased and whole-cell patch-clamp recording revealed that excitatory synaptic function was obviously attenuated after T3 treatment. Notably, pharmacological activation of AMPAR or NMDAR by intraperitoneal injection of CX546, an AMPAR agonist, or NMDA, an NMDAR agonist can restore excitatory synaptic function and corrected impaired learning and memory deficit in hyperthyroid mice. Together, our findings uncovered a previously unrecognized AMPAR and NMDAR-dependent mechanism involved in regulating hippocampal excitatory synaptic transmission and learning and memory disorders in hyperthyroidism.

Metabolic disorders induced by arsenic exposure have attracted great public concern. However, it remains unclear whether hypothalamus-based central regulation mechanisms are involved in this process. Here, we exposed mice to 100 μg/L arsenic in drinking water and established a chronic arsenic exposure model. Our study revealed that chronic arsenic exposure caused metabolic disorders in mice including impaired glucose metabolism and decreased energy expenditure. Arsenic exposure also impaired glucose sensing and the activation of proopiomelanocortin (POMC) neurons in the hypothalamus. In particular, arsenic exposure damaged the plasticity of hypothalamic astrocytic process. Further research revealed that arsenic exposure inhibited the expression of sex-determining region Y-Box 2 (SOX2), which decreased the expression level of insulin receptors (INSRs) and the phosphorylation of AKT. The conditional deletion of astrocytic SOX2 exacerbated arsenic-induced effects on metabolic disorders, the impairment of hypothalamic astrocytic processes, and the inhibition of INSR/AKT signaling. Furthermore, the arsenic-induced impairment of astrocytic processes and inhibitory effects on INSR/AKT signaling were reversed by SOX2 overexpression in primary hypothalamic astrocytes. Together, we demonstrated here that chronic arsenic exposure caused metabolic disorders by impairing SOX2-modulated hypothalamic astrocytic process plasticity in mice. Our study provides evidence of novel central regulatory mechanisms underlying arsenic-induced metabolic disorders and emphasizes the crucial role of SOX2 in regulating the process plasticity of adult astrocytes.

Multidrug resistance (MDR) is the main challenge faced by cancer chemotherapy. Drug-conjugate offers a promising strategy for breast cancer therapy. In this regard, we developed a DNVM multifunctional drug delivery system by crosslinking doxorubicin (DOX) and vitamin E succinate (VES) with a pH-sensitive hydrazone bond and then encapsulated the DOX-NN-VES prodrug into pH-sensitive hyaluronic acid-2-(octadecyloxy)-1,3-dioxan-5-amine (HOD) micelles. DOX resistant MCF-7/ADR cell were adopted as a model to study the capability and mechanism of MDR reversal. DNVM exhibited much higher cytotoxicity and cell uptake efficiency compared with that of acid-insensitive DOX-VES loaded HOD micelles (DVSM) and DOX loaded HOD micelles (DOXM), indicating the better capacity of DNVM for the reversal of MDR. Moreover, DNVM prevented drug efflux more effectively, inhibited the expression of P-gp, induced excessive production of reactive oxygen species and affected the expression of apoptosis-related proteins. In vivo experiments showed that DNVM significantly inhibited the tumor growth with no obvious changes in the body weight of MCF-7/ADR cells-bearing nude mice. The results suggested that the “double gain” DNVM can synergistically enhance the efficacy of chemotherapeutics for DOX resistant tumor cells and has the potential to overcome tumor MDR.

The tribological performances of proppant particle-shale rock contact determine the quality of hydraulic fracturing. In this work, the tribological property of quartz sand particle-shale rock contact was investigated. The friction of the contact is highly affected by lubricating media at the interface and water saturation state of the particles and the shale rock, which is related to water as a lubricant for the contact and sand particles softened by absorbing water, respectively. Under lubrication by guar gum aqueous solution, the friction of the contact was found to change with guar gum concentration while normal load and sliding speed exhibited little influence.

Morphological characteristics are the leading indicators of the health status of birds. To explore the effects of heavy metals on bird morphometry in natural populations, tree sparrows (Passer montanus) were studied in a polluted site [Baiyin (BY)] and a relatively unpolluted site [Liujiaxia (LJX)]. This study aimed to examine whether morphological variables, the fluctuating asymmetry (FA) of the wing, tarsus, and toe length, were associated with heavy metals (Cu, Zn, Pb, and Cd) and Ca levels in different tissues and feces of adults and nestlings. Results showed that adults collected from BY contained relatively higher heavy metal concentrations and lower Ca concentrations in different tissues than those from LJX. Smaller body sizes and higher FA levels of adults and nestlings were found in BY than in LJX. Although higher heavy metal concentrations in some tissues were associated with smaller morphological characteristics of adults, the effects were not obvious in nestlings. The most correlated heavy metal with as many characteristics was heavy metal in primary feather in both sites, and the most affected characteristic was body mass in BY. The FA values of adults and nestlings in BY were positively affected by heavy metal concentrations in different tissues and feces. The growth rate of wing and tarsus length of nestlings in BY were negatively affected by the FA values of wing and tarsus length, respectively. Taken together, environmental metal pollution might affect the morphological characteristics of tree sparrows. These findings suggest that the morphological characteristics of tree sparrows, especially FA, can be used as indicators of metal pollution, underscoring the importance of measuring morphological characteristics in avian ecotoxicology field studies.

The difficulty of dispersing nanofillers and the insufficient of flexibility remains major obstacle to the expansion of nanocomposite applications. In this study, silk fibroin (SF) based nanocomposite materials were obtained using glycerol plasticized SF as the matrix and short polymer nanofibers as the reinforcing phase. Highly flexible SF films with silk I structure were fabricated by using glycerol as a plasticizer. More importantly, plasticizer glycerol significantly improved the homogeneous dispersion of short PVA-co-PE nanofibers in SF films through interfacial interactions, forming flexible and robust nanofiber-reinforced composite films. FTIR and XRD results showed that no significant change was found on secondary structure and crystal structure of SF protein after adding PVA-co-PE nanofibers. It was found that nanofiber content showed significant influence on the mechanical behavior of nanocomposite films, where the addition of 5–10% short PVA-co-PE nanofibers is preferred for achieving enhanced flexibility and strength. This study provides new options for the fabrication of robust and flexible SF nanocomposites for functional applications.

The aim of this research is to carry out pseudo-static tests and investigate the seismic behaviour of the endplate composite joints of concrete-filled steel tubular (CFST) columns using blind bolts. Four full-scale blind-bolted endplate composite joints of a reinforced concrete (RC) slab to circular or square CFST columns were subjected to lateral cyclic displacements. Thereafter, the data obtained were used to evaluate the seismic performance of the typical composite joints from many aspects, such as hysteretic response, strength and rigidity degradation, ductility and energy dissipation capacity. In addition, failure modes were summarized based on the test phenomena; the influence of the column section and endplate types on the seismic performance of the joints was discussed in detail. The findings of the experiment demonstrate that the blind-bolted endplate composite joints possess appropriate ductility and adequate energy dissipation and, through reasonable design, they can satisfy the anti-seismic requirements in most seismic zones.

Poly(3-hydroxybutyrate) (PHB) is an attractive biopolymer potential for various applications, but its brittle nature is a big handicap. In this study, we proposed lignin copolymers as mechanical reinforcement agents for PHB. A series of lignin copolymers (random and block) were synthesized via the solvent free ring-opening polymerization (ROP) of β-butyrolactone and/or e-caprolactone onto lignin core. The lignin copolymers were characterized by nuclear magnetic resonance (NMR), gel permeation chromatography (GPC) and differential scanning calorimetry (DSC). Next, these lignin copolymers were incorporated into PHB nanofibers as reinforcement fillers, in order to improve their mechanical properties. It is found that the lignin block copolymer with poly(e-caprolactone) (PCL) segment followed by PHB segment (LPC + H) displayed the best mechanical improvement. Tensile strength of PHB nanofibers enhanced from 1.81 MPa to 3.13 MPa, and elongation at break increased from 15% of 55%. In the reinforced system, lignin plays as a rigid core, PCL acts a rubbery layer and PHB segment forms strong bonding with fiber matrix. Moreover, PHB/lignin nanofibers were demonstrated with superior biodegradability and biocompatibility, indicating that the new nanofibrous system holds great potential for biomedical applications.

Over the past decades, hydraulic fracturing has been adopted extensively in the petroleum field to stimulate the growth of shale gas production. To better understand hydraulic fracturing, the frictional behavior of shale rock-silica contacts was investigated. Data from experiments show that friction coefficient of the contact gradually increases from 0.2 to somewhere in the range of 0.3–0.4, and then reaches steady state with increasing load, which is directly related to the transformation from the mixed to the boundary lubrication regime of guar gum aqueous solutions. Moreover, the friction coefficient of the contact has no trend with the increasing concentration of guar gum aqueous solution, which is attributed to rheological performances of guar gum in contacts.