Carrier Transport Regulation of Pixel Graphene Transparent Electrodes for Active-Matrix Organic Light-Emitting Diode Display.

Integrating a graphene transparent electrode (TE) matrix with driving circuits is essential for the practical use of graphene in optoelectronics such as active-matrix organic light-emitting diode (OLED) display, however it is disabled by the transport of carriers between graphene pixels after deposition of a semiconductor functional layer caused by the atomic thickness of graphene. Here, the carrier transport regulation of a graphene TE matrix by using an insulating polyethyleneimine (PEIE) layer is reported. The PEIE forms an ultrathin uniform film (≤10 nm) to fill the gap of the graphene matrix, blocking horizontal electron transport between graphene pixels. Meanwhile, it can reduce the work function of graphene, improving the vertical electron injection through electron tunneling. This enables the fabrication of inverted OLED pixels with record high current and power efficiencies of 90.7 cd A-1 and 89.1 lm W-1 , respectively. By integrating these inverted OLED pixels with a carbon nanotube-based thin-film transistor (CNT-TFT)-driven circuit, an inch-size flexible active-matrix OLED display is demonstrated, in which all OLED pixels are independently controlled by CNT-TFTs. This research paves a way for the application of graphene-like atomically thin TE pixels in flexible optoelectronics such as displays, smart wearables, and free-form surface lighting.

Role of COX-2/PGE2 signaling pathway in the apoptosis of rat ovarian granulosa cells induced by MEHP.

OBJECTIVE: MEHP, as the metabolite of DEHP, is a widely used environmental endocrine disruptor. Ovarian granulosa cells participate in maintaining the function of ovary and COX2/PGE2 pathway may regulate the function of granulosa cells. We aimed to explore how COX-2/PGE2 pathway affects cell apoptosis in ovarian granulosa cells caused by MEHP. METHODS: Primary rat ovarian granulosa cells were treated with MEHP (0, 200, 250, 300 and 350 µM) for 48 h. Adenovirus was used for over-expression of COX-2 gene. The cell viability was tested with CCK8 kits. The apoptosis level was tested by flow cytometry. The levels of PGE2 were tested with ELISA kits. The expression levels of COX-2/PGE2 pathway related genes, ovulation-related genes and apoptosis-related genes, were measured with RT-qPCR and Western blot. RESULTS: MEHP decreased the cell viability. After MEHP exposure, the cell apoptosis level increased. The level of PGE2 markedly decreased. The expression levels of COX-2/PGE2 pathway related genes, ovulation-related genes and anti-apoptotic genes decreased; the expression levels of pro-apoptotic genes increased. The apoptosis level was alleviated after over-expression of COX-2, and the level of PGE2 slightly increased. The expression levels of PTGER2 and PTGER4, and the levels of ovulation-related genes increased; the levels of pro-apoptotic genes decreased. CONCLUSION: MEHP can cause cell apoptosis by down-regulating the levels of ovulation-related genes via COX-2/PGE2 pathway in rat ovarian granulosa cells.

Electrospinning micro-nanofibers immobilized aerobic denitrifying bacteria for efficient nitrogen removal in wastewater.

Electrospinning micro-nanofibers with exceptional physicochemical properties and biocompatibility are becoming popular in the medical field. These features indicate its potential application as microbial immobilized carriers in wastewater treatment. Here, aerobic denitrifying bacteria were immobilized on micro-nanofibers, which were prepared using different concentrations of polyacrylonitrile (PAN) solution (8%, 12% and 15%). The results of diameter distribution, specific surface area and average pore diameter indicated that 15% PAN micro-nanofibers with tighter surface structure were not suitable as microbial carriers. The bacterial load results showed that the cell density (OD600) and total protein of 12% PAN micro-nanofibers were 107.14% and 106.28% higher than those of 8% PAN micro-nanofibers. Subsequently, the 12% PAN micro-nanofibers were selected for aerobic denitrification under the different C/N ratios (1.5-10), and stable performance was obtained. Bacterial community analysis further manifested that the micro-nanofibers effectively immobilized bacteria and enriched bacterial structure under the high C/N ratios. Therefore, the feasibility of micro-nanofibers as microbial carriers was confirmed. This work was of great significance for promoting the application of electrospinning for microbial immobilization in wastewater treatment.

Di(2-ethylhexyl) phthalate induced thyroid toxicity via endoplasmic reticulum stress: In vivo and in vitro study.

Di(2-ethylhexyl) phthalate (DEHP) could induce thyroid injury but the mechanism was unclear. This study combined in vivo and in vitro experiments to clarify the mechanism. In vivo, the offspring of Sprague Dawley rats were gavaged with different doses of DEHP (5, 50, and 250 mg/[kg⋅d]) from in utero to 12 weeks-old. Transcriptome sequencing was used to detect the mRNA expression profile of the offspring's thyroids. Differentially expressed genes were identified, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. In vitro, Nthy-ori 3-1 cells were exposed to DEHP's metabolite mono (2-ethylhexyl) phthalate (MEHP) to verify the pathway we found by KEGG analysis. The results indicated that DEHP could disorder the thyroid hormones. Compared with the offspring in control group, the mRNA levels of 656 genes were upregulated in the offspring exposed to 50 mg/(kg⋅d) DEHP. The upregulated genes were enriched in the pathway of "protein processing in the endoplasmic reticulum (ER)." It indicated that the ER stress might play significant role in the thyroid toxicity induced by DEHP. In vitro, the mitochondrial membrane potential (ΔΨm) level of cells was decreased while the reactive oxygen species level was increased after MEHP exposure. MEHP increased the intracellular Ca2+ level and induced ER stress. After ER stress was inhibited by the 4-phenylbutyric acid, the thyroid toxicity caused by MEHP was alleviated. Taken together, our results indicated that DEHP could induce thyroid toxicity by activating ER stress.

PM2.5 promoted lipid accumulation in macrophage via inhibiting JAK2/STAT3 signaling pathways and aggravating the inflammatory reaction.

BACKGROUND: Abnormal lipid accumulation in macrophages may lead to macrophages foaming, which is the most important pathological process of atherosclerosis. Atmospheric PM2.5 could enter the blood circulation and further affect the lipid metabolism of macrophages. But the underlying mechanism is not unclear. This study was undertaken to clarify the effect of PM2.5 on lipid metabolism in macrophages, and to explore the role of inflammatory reaction and JAK2/STAT3 signaling pathway in this process. METHOD: Macrophages derived from THP-1 cells were exposed to PM2.5 (0,100,200,400 µg/mL) for 6 h and 12 h. STAT3 agonist ColivelinTFA is used to specifically excite STAT3. The survival rate of macrophages was detected by CCK-8. The lipid levels in macrophages were detected by colorimetry. The levels of inflammatory factors secreted by macrophages were detected by ELISA. Q-PCR was used to detect the mRNA expression levels, and Western Blot was used to detect the protein expression levels of JAK2/STAT3 pathway genes. RESULT: The survival rate of macrophages was reduced by PM2.5, and the levels of TG, T-CHO and LDL-C of macrophages exposed to PM2.5 were increased. PM2.5 led to the increasing level of IL-6 and the decreasing level of IL-4, and the JAK2/STAT3 signaling pathway was inhibited by PM2.5. Colivelin TFA significantly decreased the increasing levels of TG, T-CHO and LDL-C levels, and increased the decreasing mRNA levels of IL-4, and LPL induced by PM2.5 (p < 0.05). DISCUSSION: PM2.5 could cause the lipid accumulation of macrophages by inhibiting the JAK2/STAT3 signaling pathway, and inflammatory responses may be involved in this process.

Effect of Notch pathway on lipid accumulation induced by mono-2-ethylhexyl phthalate on 3T3-L1 cells.

BACKGROUND: Mono-2-ethylhexyl phthalate (MEHP) is a major metabolite of di (2-ethylhexyl) phthalate (DEHP). Our previous researches have shown that MEHP can induce lipid accumulation in preadipocytes, while, the underlying mechanism is unclear. The present study was undertaken to clarify the effect of Notch pathway on lipid accumulation induced by MEHP. METHODS: 3T3-L1 preadipocytes were exposed to MEHP (0, 10, 50, 250 µM and 0.1%DMSO) for the whole differentiation phase. Then the level of TG and cell cycle were detected. RT-PCR was used to detect the mRNA expression and Western blot was used to detect the expression of protein by Notch pathway genes and lipid metabolic related genes. RESULTS: In this study, the level of TG in the 250 µM and 250 µM MEHP groups was significantly higher than that in the control, DMSO and 10 µM MEHP groups (P < 0.05). The relative mRNA level of Notch-1, Notch-3, Notch-4, Jagged-2 and Dll-4 in 250 µM group was higher than other groups (P < 0.05). The expression of Notch signal pathway proteins increased in MEHP treated groups, and the expression of Notch-2, Jagged-1, Jagged-2, Dll-1 and Dll-4 in 250 µM group were significantly higher than control group (P < 0.05). The expression of lipid metabolic related gene mRNA and protein increased in MEHP treated groups, and 250 µM MEHP group was higher than other groups (P < 0.05). The intracellular TG content was significantly correlated with the expression levels of Notch-1 and Jagged-2 mRNA (P < 0.05). CONCLUSION: In this study, we have found that MEHP exposure could increase the TG content in 3T3-L1 cells. The expression of Notch pathway mRNA and proteins were disturbed by the MEHP. Notch-1 and its ligand Jagged-2 play a critical role in the abnormal lipid metabolism in 3T3-L1 cells caused by MEHP.

Exposure to PM2.5 affects blood lipid levels in asthmatic rats through notch signaling pathway.

BACKGROUND: Epidemiological studies have confirmed atmospheric PM2.5 could affect asthma, and dyslipidemia may be related to pathogenesis of asthma. Recent studies show Notch ligands had lipid combination domains which are responsible for regulating lipid levels. However, the effect of PM2.5 on asthmatic rats' lipid levels and the role of Notch signaling pathway is unclear. METHODS: Rats were treat with ovalbumin (OVA) to establish asthma models. Notch signaling pathway inhibitor (DAPT) was injected intraperitoneally. Asthmatic and healthy rats were exposed to different concentrations of PM2.5. Lung tissues were collected and the expression of Hes1 protein was detected by Western Blot. Blood samples were collected to detect the serum lipid levels. RESULTS: Hes1 expression levels in healthy and asthma pathway inhibition groups were lower than those in control groups. Compared with control group, rats exposed to PM2.5 in middle and high dose, the levels of TG and TC were decreased. Similar results were observed after exposure to the same concentration of PM2.5 in asthmatic rats. Rats, which were exposed to PM2.5 after being established the asthma model successfully, could exhibit more significant dyslipidemia than those with direct exposure. After Notch signaling pathway inhibited, TC and LDL in asthma pathway inhibition group were lower than those in healthy group. CONCLUSIONS: PM2.5 can affect the lipid levels of asthmatic rats through the Notch signaling pathway.

Mono-2-ethylhexyl phthalate (MEHP) promoted lipid accumulation via JAK2/STAT5 and aggravated oxidative stress in BRL-3A cells.

Mono-2-ethylhexyl phthalate (MEHP), as the major metabolite of Di-(2-ethylhexyl) phthalate (DEHP), can induce lipid accumulation in hepatocytes and further leads to non-alcoholic fatty liver disease (NAFLD), while the underlying mechanism is unclear. We aim to clarify the effects of JAK2/STAT5 pathway on lipid accumulation induced by MEHP and the role of oxidation stress in NAFLD. BRL-3A hepatocytes were exposed to MEHP (0, 10, 50, 100 and 200 µM) for 24 h and 48 h. Then the lipid droplets in cells were observed by Oil-Red-O staining and quantified by isopropyl alcohol. The levels of TG, SOD, TBARS, AST and ALT were all detected by commercial kits. RT-PCR was used to detect mRNA expression, and western blotting was used to detect the expression of proteins encoded by JAK2/STAT5 pathway genes and lipid metabolism-related genes. As a result, MEHP promoted the lipid synthesis and accumulation in BRL-3A cells. MEHP down-regulated the expression and inhibited the activation of JAK2/STAT5. Moreover, the lipid metabolism-related kinases levels were elevated after MEHP exposure. In addition, the SOD levels were gradually decreased and the TBARS levels were increased in MEHP-treated groups. The lipid metabolism-related proteins levels were correlated with the oxidation stress levels. Furthermore, the ALT and AST levels were elevated after MEHP exposure. Therefore, we concluded that MEHP led to lipid accumulation through inhibiting JAK2/STAT5 pathway, resulted in damaging liver parenchyma and NAFLD by aggravating oxidation stress.

The effect of di-2-ethylhexyl phthalate on inflammation and lipid metabolic disorder in rats.

BACKGROUND: Plasticizer di-2-ethylhexyl phthalate (DEHP) can induce lipid metabolic disorder. There was a chronic low level inflammatory response in adipose tissue of patients with lipid metabolic disorder. But the effect of inflammation on lipid metabolic disorder induced by DEHP is unclear. The present study was undertaken to explore the effect of di-2-ethylhexyl phthalate on inflammation and lipid metabolic disorder in rats. METHODS: Eighty healthy 21-day-old Wistar rats were randomly divided into 4 groups and administered DEHP by gavage at 0, 5, 50, and 500 mg/kg/ d for 8 weeks. Morphological changes of adipose tissue, the levels of IL-1ß, TNF-α, LEP, and ADP in rat serum and adipose tissue, the serum TC, TG, HDL-C and LDL-C, the mRNA and protein expression levels of lipid metabolism-related gene CEBP/ß and inflammation-related gene CD68 were measured. RESULTS: After exposure to DEHP, the weight of rats in the high dose group was significantly higher than that in the control group (p < 0.05). And the number of adipose tissue cells in the medium-dose and high-dose DEHP groups increased, with much more macrophage infiltrated. The levels of LDL-C, HDL-C, TC in serum and LEP in adipose tissue of rats exposed to 500 mg/kg DEHP were significantly higher than those in the control group (p < 0.05); while the level of ADP in adipose tissue in rats exposed to DEHP was significantly lower (p < 0.05). The levels of IL-1ß and TNF-α in surum and adipose tissue of rats exposed to DEHP were significantly higher than those in the control group (p < 0.05). The mRNA and protein expression levels of CEBP/ß and CD68 in adipose tissue of rats exposed to DEHP were significantly higher than those in the control group. The TC, LEP and ADP Levels of rats were significantly different among different subgroup of IL-1ß and TNF-α, and in high level subgroup, the TC, LEP and ADP Levels were increased. The levels of TC and LEP was increased in high level subgroup of CD68. CONCLUSION: DEHP induced more macrophage infiltrated in adipose tissue of rats, promoted the secretion of IL-1ß, TNF-α and the formation of inflammation, and disturbed the normal lipid metabolism and lead to lipid metabolic disorders. What is more, the levels of inflammation were associated with the lipid levels.

Urinary levels of phthalate metabolites and their association with lifestyle behaviors in Chinese adolescents and young adults.

BACKGROUND: Adolescence and young adulthood are critical periods of human growth and development. Phthalates are environmental endocrine disruptors, and their health hazards in adolescents and young adults cannot be ignored. This study was undertaken to assess phthalate exposure and determine the associations between lifestyle behaviors and phthalate metabolite levels in Chinese adolescents and young adults. METHODS: Four hundred and seventy-eight adolescents and young adults aged 16-20 years were included in this study. The levels of mono-ethyl phthalate (MEP), mono-butyl phthalate (MBP), mono-(2-ethylhexyl) phthalate (MEHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP) and mono-(2-carboxmethyl)-hexyl phthalate (MCMHP) in the subjects' urine were measured by high-performance liquid chromatography-tandem mass spectrometry. The estimated daily intake (EDI) and hazard index (HI) of phthalates were calculated based on urinary metabolite levels. Relevant information on the subjects was collected via questionnaires. The associations between phthalate metabolite levels and lifestyle behaviors were examined using the independent-sample t-test, Mann-Whitney test and multiple linear regression. RESULTS: In this study, the detection rates of all seven metabolites were >98%. The highest median metabolite concentration was MBP, which was 43.00 µg/L (33.11 µg/g creatinine). The highest median EDI was for di-(2-ethylhexyl) phthalate (DEHP), which was 2.40 µg/kg-bw/day (volume-based) and 1.51 µg/kg-bw/day (creatinine-based). 2.7% (volume-based) and 1.0% (creatinine-based) of the subjects showed excessive HITDI (HI of the tolerable daily intake) values, which indicated the cumulative risk of anti-androgenic effects. Furthermore, factors significantly associated with phthalate metabolite levels included the use of plastic food packages (DEHP metabolites), physical exercise (MEOHP), the frequency of fast food consumption (MBP), and the frequency of skin care cosmetics and color cosmetics use (MEP). CONCLUSION: Our results suggest that Chinese adolescents and young adults are widely exposed to phthalates and their metabolite levels are influenced by lifestyle behaviors.

Suppression or Inhibition of VEGFs on Splenic Angiosarcoma Cell with Traditional Chinese Medicine Zhi Gan Cao.

Primary splenic angiosarcoma is a very rare disease that causes the development of malignant tumors in the vascular endothelium of the splenic sinuses. Moreover, the disease maintains a very low survival rate for patients to live over 5 years, which is relatively low when compared to another splenic cancer, splenic lymphomas. The treatment options for splenic angiosarcoma narrow down to surgical removal or radiation combined with chemotherapy, but both cost a lot, so discovering potential alternative treatments may eventually increase the possible survival rate. Ginseng and Zhi Gan Cao are both common herbs in Traditional Chinese Medicine (TCM); however, the price of Ginseng is much higher than that of Zhi Gan Cao. A possible reason could be the frequent studies and researches over Ginseng's active ingredient, ginsenoside rh2 or rg3 as they are both potent cancer treatments. The reason to study Zhi Gan Cao and predict its possible potential in cancer treatment is due to the similarity between its active ingredient and the active ingredient in Ginseng, namely, ginsenoside rh2 and licorice saponins. Both TCM contain the active ingredient, triterpenoid saponin, as their main composition, and the further text will predict the possible research and results that may be taken in vitro to reveal the question of whether licorice saponin has the potential to become a major treatment for splenic angiosarcoma or not.

Insight into the mechanism of DNA methylation and miRNA-mRNA regulatory network in ischemic stroke.

BACKGROUND: Epigenetic changes, such as DNA methylation and miRNA-target gene mechanisms, have recently emerged as key provokers in Ischemic stroke (IS) onset. However, cellular and molecular events harboring these epigenetic alterations are poorly understood. Therefore, the present study aimed to explore the potential biomarkers and therapeutic targets for IS. METHODS: miRNAs, mRNAs and DNA methylation datasets of IS were derived from the GEO database and normalized by PCA sample analysis. Differentially expressed genes (DEGs) were identified, and GO and KEGG enrichment analyses were performed. The overlapped genes were utilized to construct a protein-protein interaction network (PPI). Meanwhile, differentially expressed mRNAs and miRNAs interaction pairs were obtained from the miRDB, TargetScan, miRanda, miRMap and miTarBase databases. We constructed differential miRNA-target gene regulatory networks based on mRNA-miRNA interactions. RESULTS: A total of 27 up-regulated and 15 down-regulated differential miRNAs were identified. Dataset analysis identified 1053 and 132 up-regulated and 1294 and 9068 down-regulated differentially expressed genes in the GSE16561 and GSE140275 datasets, respectively. Moreover, 9301 hypermethylated and 3356 hypomethylated differentially methylated sites were also identified. Moreover, DEGs were enriched in terms related to translation, peptide biosynthesis, gene expression, autophagy, Th1 and Th2 cell differentiation, primary immunodeficiency, oxidative phosphorylation and T cell receptor signaling pathway. MRPS9, MRPL22, MRPL32 and RPS15 were identified as hub genes. Finally, a differential miRNA-target gene regulatory network was constructed. CONCLUSIONS: RPS15, along with hsa-miR-363-3p and hsa-miR-320e have been identified in the differential DNA methylation protein interaction network and miRNA-target gene regulatory network, respectively. These findings strongly posit the differentially expressed miRNAs as potential biomarkers to improve ischemic stroke diagnosis and prognosis.

Preparation and luminescence properties of Ba2P2O7:Dy3+, Ce3+ phosphors.

In this paper, Ba2-x-yP2O7:xDy3+,yCe3+ phosphors are synthesized by calcining the precursor via chemical co-precipitation. The phase structure, excitation and emission spectra, thermal stability, the chromatic performance of phosphors, and energy transfer from Ce3+ to Dy3+ are studied and discussed. The results indicate the samples keep a stable crystal structure as a high-temperature σ-Ba2P2O7 phase with two different coordination of Ba2+ sites. Ba2P2O7:Dy3+ phosphors can be effectively excited by 349 nm n-UV light and emit 485 nm blue light and a relatively stronger yellow light peaking at 575 nm, corresponding to 4F9/2→6H15/2 and 4F9/2→6H13/2 transitions of Dy3+, implying that Dy3+ mainly occupies the non-inversion symmetric sites. By contrast, Ba2P2O7:Ce3+ phosphors exhibit a broadband of excitation peaking at 312 nm, and two symmetrical emission peaks at 336 nm and 359 nm from 5d1→4F5/2 and 5d1→4F7/2 transitions of Ce3+, showing Ce3+ should merely be presumed to occupy Ba1 site. After Dy3+ and Ce3+ are co-doped, Ba2P2O7:Dy3+, Ce3+ phosphors exhibit the enhanced characteristic blue and yellow emission of Dy3+ with nearly equal intensity under excitation at 323 nm, meaning Ce3+ co-doping increases the symmetry of Dy3+ site as well as the sensitizer. Simultaneously, energy transfer from Dy3+ to Ce3+ is found and discussed. The thermal stability of co-doped phosphors was characterized and briefly analyzed. The color coordinates of Ba2P2O7:Dy3+ phosphors fall in the yellow-green region near the white light, while the emission moves towards the blue-green region after the Ce3+ is co-doped.

Controllable and biocompatible 3D bioprinting technology for microorganisms: Fundamental, environmental applications and challenges.

3D bioprinting is a new 3D manufacturing technology, that can be used to accurately distribute and load microorganisms to form microbial active materials with multiple complex functions. Based on the 3D printing of human cells in tissue engineering, 3D bioprinting technology has been developed. Although 3D bioprinting technology is still immature, it shows great potential in the environmental field. Due to the precise programming control and multi-printing pathway, 3D bioprinting technology provides a high-throughput method based on micron-level patterning for a wide range of environmental microbiological engineering applications, which makes it an on-demand, multi-functional manufacturing technology. To date, 3D bioprinting technology has been employed in microbial fuel cells, biofilm material preparation, microbial catalysts and 4D bioprinting with time dimension functions. Nevertheless, current 3D bioprinting technology faces technical challenges in improving the mechanical properties of materials, developing specific bioinks to adapt to different strains, and exploring 4D bioprinting for intelligent applications. Hence, this review systematically analyzes the basic technical principles of 3D bioprinting, bioinks materials and their applications in the environmental field, and proposes the challenges and future prospects of 3D bioprinting in the environmental field. Combined with the current development of microbial enhancement technology in the environmental field, 3D bioprinting will be developed into an enabling platform for multifunctional microorganisms and facilitate greater control of in situ directional reactions.

Energy-Based Continuous Inverse Optimal Control.

The problem of continuous inverse optimal control (over finite time horizon) is to learn the unknown cost function over the sequence of continuous control variables from expert demonstrations. In this article, we study this fundamental problem in the framework of energy-based model (EBM), where the observed expert trajectories are assumed to be random samples from a probability density function defined as the exponential of the negative cost function up to a normalizing constant. The parameters of the cost function are learned by maximum likelihood via an "analysis by synthesis" scheme, which iterates: 1) synthesis step: sample the synthesized trajectories from the current probability density using the Langevin dynamics via backpropagation through time and 2) analysis step: update the model parameters based on the statistical difference between the synthesized trajectories and the observed trajectories. Given the fact that an efficient optimization algorithm is usually available for an optimal control problem, we also consider a convenient approximation of the above learning method, where we replace the sampling in the synthesis step by optimization. Moreover, to make the sampling or optimization more efficient, we propose to train the EBM simultaneously with a top-down trajectory generator via cooperative learning, where the trajectory generator is used to fast initialize the synthesis step of the EBM. We demonstrate the proposed methods on autonomous driving tasks and show that they can learn suitable cost functions for optimal control.

Luteolin and triptolide: Potential therapeutic compounds for post-stroke depression via protein STAT.

Post stroke depression (PSD) is a common neuropsychiatric complication following stroke closely associated with the immune system. The development of medications for PSD remains to be a considerable challenge due to the unclear mechanism of PSD. Multiple researches agree that the functions of gene ontology (GO) are efficient for the investigation of disease mechanisms, and DeepPurpose (DP) is extremely valuable for the mining of new drugs. However, GO terms and DP have not yet been applied to explore the pathogenesis and drug treatment of PSD. This study aimed to interpret the mechanism of PSD and discover important drug candidates targeting risk proteins, based on immune-related risk GO functions and informatics algorithms. According to the risk genes of PSD, we identified 335 immune-related risk GO functions and 37 compounds. Based on the construction of the GO function network, we found that STAT protein may be a pivot protein in underlying the mechanism of PSD. Additionally, we also established networks of Protein-Protein Interaction as well as Gene-GO function to facilitate the evaluation of key genes. Based on DP, a total of 37 candidate compounds targeting 7 key proteins were identified with a potential for the therapy of PSD. Furthermore, we noted that the mechanisms by which luteolin and triptolide acting on STAT-related GO function might involve three crucial pathways, including specifically hsa04010 (MAPK signaling pathway), hsa04151 (PI3K-Akt signaling pathway) and hsa04060 (Cytokine-cytokine receptor interaction). Thus, this study provided fresh and powerful information for the mechanism and therapeutic strategies of PSD.

Preparation of Cod Skin Collagen Peptides/Chitosan-Based Temperature-Sensitive Gel and Its Anti-Photoaging Effect in Skin.

Background: Photoaging decreases quality of life and increases the risk of skin cancer, underscoring the urgent need to explore natural, high-efficacy, anti-skin photoaging (SP) active substances. Methods: In this study, a gel (CS/CSCPs/ß-GP gel) was prepared using chitosan (CS) and sodium ß-glycerophosphate (ß-GP) through crosslinking with small molecular CSCPs as the carried drug. We evaluated its structural characteristics and properties. The effect of CS/CSCPs/ß-GP gel on the degree of ultraviolet (UV)-induced skin aging of mice was investigated through comparative analysis of skin damage, the integrity of collagen tissues and elastic fibers, levels of reactive oxygen species (ROS) and key inflammatory factors (tumor necrosis factor [TNF]-α and interleukin [IL]-1ß, IL-6, and IL-10), and tissue expression of matrix metalloproteinase-3 (MMP-3) after repeated UV irradiation in a nude mice SP model. Results: The results showed that CS/CSCPs/ß-GP gel was successfully prepared and had the desired characteristics. Compared with CSCPs alone, the CS/CSCPs/ß-GP gel more evidently improved typical photoaging characteristics on mouse dorsal skin. It also increased the moisture content, causing the skin to become glossy and elastic. Pathological skin analysis revealed that this peptide-carrying gel can effectively inhibit epidermal thickening, reduce tissue inflammatory infiltration, suppress collagen fiber degradation, increase the collagen content, alleviate structural elastic fiber damage, and significantly inhibit abnormal MMP-3 expression. In addition, biochemical analysis showed that the CS/CSCPs/ß-GP gel can effectively inhibit the elevated expressions of ROS and key proinflammatory factors (TNF-α, IL-1ß, IL-6) in photoaging skin tissues and promote expression of the anti-inflammatory factor IL-10. Conclusion: SP can cause many clinical skin diseases, such as solar freckle-like nevus, solar keratosis, cutaneous melanoma, and squamous cell carcinoma. CSCPs are a high-efficacy anti-SP natural active substance and CS/CSCPs/ß-GP gel can synergistically enhance the CSCPs' anti-SP effect. The mechanism is likely related to the inhibited activation of ROS/nuclear transcription factor-κB signaling and the expression of downstream inflammatory factors.

PM2.5 induces the abnormal lipid metabolism and leads to atherosclerosis via Notch signaling pathway in rats.

PM2.5 can affect the lipid metabolism and cause atherosclerosis. Abnormal lipid metabolism is a sever risk factor of atherosclerosis and the underlying molecular mechanism still remains unclear. In this study, GPL16956 Agilent-045997 Arraystar human lncRNA microarray V3 (Probe Name Version) platform was used to detect the different genes of lipid metabolism between the normal arterial intima and advanced atherosclerotic plaque, which were downloaded from GEO database. A high-fat diet and vitamin D3 were administered to Wistar rats to establish the atherosclerotic model and another normal healthy 56 rats were used as the non-atherosclerotic exposure groups. The atherosclerotic rats and non-atherosclerotic rats were randomly divided into 4 PM2.5 groups (0, 1.5, 7.5, 37.5 mg/kg), respectively. The results of bioinformatics showed changes in the Notch1, Dll1, Hes1, LDLR and ABCG1 levels. PM2.5 exposure could produce damage to the physiological structure of the aorta, and aggravate atherosclerosis in rats from both non-atherosclerotic and atherosclerotic groups. With the increase of the exposure dose, the levels of TC and TG significantly increased. PM2.5 exposure significantly affected the expression levels of PPARγ, ABCA1, LDLR, CD36, SR-BI and SREBP2. PM2.5 exposure could also affect the expression levels of the Notch signaling pathways which was significantly correlated with the levels of TC and TG. The results proved that PM2.5 exposure could induce and aggravate the atherosclerosis in rats by disrupting lipid metabolism in which Notch signaling pathway may play a significant role.

Inhibition of the expression of rgs-3 alleviates propofol-induced decline in learning and memory in Caenorhabditis elegans.

BACKGROUND: Exposure to anesthesia leads to extensive neurodegeneration and long-term cognitive deficits in the developing brain. Caenorhabditis elegans also shows persistent behavioral changes during development after exposure to anesthetics. Clinical and rodent studies have confirmed that altered expression of the regulators of G protein signaling (RGS) in the nervous system is a factor contributing to neurodegenerative and psychological diseases. Evidence from preclinical studies has suggested that RGS controls drug-induced plasticity, including morphine tolerance and addiction. This study aimed to observe the effect of propofol exposure in the neurodevelopmental stage on learning and memory in the L4 stage and to study whether this effect is related to changes in rgs-3 expression. METHODS: Caenorhabditis elegans were exposed to propofol at the L1 stage, and learning and memory abilities were observed at the L4 stage. The expression of rgs-3 and the nuclear distribution of EGL-4 were determined to study the relevant mechanisms. Finally, RNA interference was performed on rgs-3-expressing cells after propofol exposure. Then, we observed their learning and memory abilities. RESULTS: Propofol time- and dose-dependently impaired the learning capacity. Propofol induced a decline in non-associative and associative long-term memory, rgs-3 upregulation, and a failure of nuclear accumulation of EGL-4/PKG in AWC neurons. Inhibition of rgs-3 could alleviate the propofol-induced changes. CONCLUSION: Inhibition of the expression of rgs-3 alleviated propofol-induced learning and memory deficits in Caenorhabditis elegans.

Insights into heavy metals shock on anammox systems: Cell structure-based mechanisms and new challenges.

Anaerobic ammonium oxidation (anammox) as a low-carbon and energy-saving technology, has shown unique advantages in the treatment of high ammonia wastewater. However, wastewater usually contains complex heavy metals (HMs), which pose a potential risk to the stable operation of the anammox system. This review systematically re-evaluates the HMs toxicity level from the inhibition effects and the inhibition recovery process, which can provide a new reference for engineering. From the perspective of anammox cell structure (extracellular, anammoxosome membrane, anammoxosome), the mechanism of HMs effects on cellular substances and metabolism is expounded. Furthermore, the challenges and research gaps for HMs inhibition in anammox research are also discussed. The clarification of material flow, energy flow and community succession under HMs shock will help further reveal the inhibition mechanism. The development of new recovery strategies such as bio-accelerators and bio-augmentation is conductive to breaking through the engineered limitations of HMs on anammox. This review provides a new perspective on the recognition of toxicity and mechanism of HMs in the anammox process, as well as the promotion of engineering applicability.