Study on the role of MYCN in retinoblastoma by inhibiting p53 and activating wnt/ßcatenin/Fra-1 signaling pathway by reducing DKK3.

Retinoblastoma (RB) is a pediatric malignancy, typically diagnosed at birth or during early childhood. The pathogenesis of RB is marked by the amplification of the Basic Helix-Loop-Helix (BHLH) Transcription Factor MYCN, which serves as a transcriptional regulator capable of binding to Dickkopf 3 (DKK3). However, the precise role of DKK3 in the malignant progression of RB cells caused by MYCN remains elusive. In the present study, the expression of MYCN was either overexpressed or interfered in RB cells. Subsequently, the expression level of DKK3 was assessed through quantitative real-time polymerase chain reaction and western blot analysis. Cell proliferation was evaluated using the Cell Counting Kit-8 assay and 5-ethynyl-2'-deoxyuridine staining, while cell cycle progression and apoptosis were analyzed by flow cytometry and western blot analysis, respectively. Additionally, the expression of proteins involved in the Wnt/ß-catenin/Fra-1/p53 signaling pathway was evaluated via western blot analysis. To gain further insights, Wnt agonists and the P53 inhibitor PFT-α were introduced into exploration. The current investigation revealed a negative correlation between the expression levels of MYCN and DKK3 in RB cells. Additionally, DKK3 overexpression inhibited cell proliferation, promoted cell apoptosis, and arrested cell cycle in RB cells with high expression of MYCN. Moreover, enhanced DKK3 expression inhibited proliferation, promoted cell cycle arrest and apoptosis of RB cells by modulating the wnt/ßcatenin/Fra-1/p53 signaling pathway. Furthermore, in vivo experiments revealed that overexpression of DKK3 inhibits the growth of RB tumors. Collectively, our findings elucidate that MYCN stimulates the Wnt/ß-catenin/Fra-1 pathway by suppressing DKK3 expression, ultimately suppressing p53 activity and contributing to malignant progression of RB.

OptoCRISPRi-HD: Engineering a Bacterial Green-Light-Activated CRISPRi System with a High Dynamic Range.

The ability to modulate gene expression is crucial for studying gene function and programming cell behaviors. Combining the reliability of CRISPRi and the precision of optogenetics, the optoCRISPRi technique is emerging as an advanced tool for live-cell gene regulation. Since previous versions of optoCRISPRi often exhibit no more than a 10-fold dynamic range due to the leakage activity, they are not suitable for targets that are sensitive to such leakage or critical for cell growth. Here, we describe a green-light-activated CRISPRi system with a high dynamic range (40 fold) and the flexibility of changing targets in Escherichia coli. Our optoCRISPRi-HD system can efficiently repress essential genes, nonessential genes, or inhibit the initiation of DNA replication. Providing a regulative system with high resolution over space-time and extensive targets, our study would facilitate further research involving complex gene networks, metabolic flux redirection, or bioprinting.

Predictive Value of Flank Pain and Gross Hematuria on Long-Term Survival in Patients With Upper Tract Urothelial Carcinoma Treated by Radical Nephroureterectomy.

Background: Assessing the prognosis preoperatively in patients with upper tract urothelial carcinoma (UTUC) remains a challenge for urologists. Gross hematuria (GH) and flank pain (FP) are the 2 most common and easily perceived symptoms of UTUC. Therefore, we aimed to investigate the prognostic values of GH and FP in patients with UTUC after undergoing radical nephroureterectomy (RNU). Methods: This article retrospectively analyzed 179 patients with UTUC who underwent RNU and examined the associations between the FP, GH, and long-term survival. After dividing patients into 4 subgroups (presenting as GH without FP, FP without GH, no FP and GH, FP with GH), we focused on the prognostic values of the 4 subgroups using univariate and multivariate analyses. We then proposed a risk stratification model for UTUC based on the independent prognostic factors for cancer-specific survival (CSS) with external validation (146 additional UTUC patients formed the validation cohort). Results: Patients with FP had worse oncological outcomes than those without FP (P < .05). After dividing the 179 patients into 4 subgroups, the "FP without GH" subgroup suffered the worst oncological outcomes (P < .001). The Cox multivariate regression analysis showed that "FP without GH" (P < .001), tumor multifocality (P = .005), and pathological stage (P = .004) were independent prognostic factors for CSS. Good performance of the risk stratification model was achieved in both the training and external validation cohorts. Conclusion: The presence of "flank pain without gross hematuria" was one of the independent risk factors of CSS and OS besides the pathological stage and tumor multifocality. To our knowledge, this is the first study that adding complaint to risk stratification model in UTUC.

Refractive status and optical components in premature infants with and without retinopathy of prematurity: A 4- to 5-year cohort study.

This study was aimed to investigate the characteristics of refractive parameters in premature infants and children aged 3-8 years with mild retinopathy of prematurity (ROP) and to explore the effects of premature delivery and mild ROP on the development of refractive status and ocular optical components. Premature infants who underwent ocular fundus oculi screening in our hospital between January 2009 and February 2011 were included and divided into the ROP group and the non-ROP group. Full-term infants were the controls. The results of the annual ocular examination conducted between 2014 and 2018 were analysed, and the refractive status, optical components, and developmental trends were compared among the three groups. The total follow-up time was 4-5 years. The prevalence of myopia and astigmatism was high in the ROP group (P < 0.05). In the non-ROP group, the prevalence of myopia was also higher than that in the control group. The prevalence of myopia increased with age in the ROP and non-ROP groups, while the prevalence of astigmatism remained unchanged. In the ROP group, the corneal refractive power was the largest, the lens was the thickest and the ocular axis was the shortest; in the control group, the corneal refractive power was the smallest, the lens was the thinnest, and the ocular axis was the longest. These parameters in the non-ROP group were between those in the two groups mentioned above (P < 0.05). The corneal refractive power was relatively stable at 3-8 years old in the three groups. The change in lens thickness was small in both the ROP group and the non-ROP group (P = 0.75, P = 0.06), and the lens became thinner in the control group (P < 0.001). The length of the ocular axis increased in the three groups. Preterm infants are more likely to develop myopia than full-term infants, and children with ROP are more likely to develop both myopia and astigmatism. Thicker lenses were the main cause of the high prevalence of myopia in premature infants with or without ROP.

Multivariate analysis of the effect of Chalazia on astigmatism in children.

BACKGROUND: Chalazion may affect visual acuity. This study aimed to evaluate refractive status of chalazia and effect of different sites, sizes, and numbers of chalazion on astigmatism. METHODS: Three hundred ninety-eight patients aged 0.5-6 years were divided into the chalazion group (491 eyes) and the control group (305 eyes). Chalazia were classified according to the site, size, and number. Refractive status was analyzed through the comparison of incidence, type, mean value and vector analysis. RESULTS: The incidence, type, refractive mean and of astigmatism in the chalazion group were higher than those in the control group, and the difference was statistically significant (P < 0.05). For comparison of the incidence, the middle-upper eyelid (50%) was highest, followed by 41.77% in the medial-upper eyelid, both higher than that in the control group (P < 0.05). In medium (54.55%) and large groups (54.76%) were higher than that in the control group (27.21%) (P < 0.05). In multiple chalazia, the astigmatism incidence for chalazion with two masses was highest (56%), much higher than that in the control group (P < 0.05). However, this difference was not significant in chalazion with ≥3 masses (P > 0.05). For comparison of the refractive mean,the medial-upper eyelid, middle-upper eyelid and medial-lower eyelid were higher than the control group (P < 0.05) (P < 0.05). The 3-5 mm and >5 mm group were higher than those in the control group and <3 mm group(P < 0.05), and the>5 mm group was larger than the 3-5 mm group，suggesting that the risk of astigmatism was higher when the size of masses > 5 mm. Astigmatism vector analysis can intuitively show the differences between groups, the results are the same as refractive astigmatism. CONCLUSION: Chalazia in children can easily lead to astigmatism, especially AR and OBL. Chalazia in the middle-upper eyelid, size ≥3 mm, and multiple chalazia (especially two masses) are risk factors of astigmatism. Invasive treatment should be performed promptly if conservative treatment cannot avoid further harm to the visual acuity due to astigmatism.

Effect of the BOPPPS model combined with case-based learning versus lecture-based learning on ophthalmology education for five-year paediatric undergraduates in Southwest China.

BACKGROUND: To investigate the effect of the bridge-in, objective, preassessment, participatory learning, post assessment, and summary (BOPPPS) model combined with case-based learning (CBL) on ophthalmology teaching for five-year paediatric undergraduates. METHODS: The effects of the BOPPPS model combined with CBL (BOPPPS-CBL) and traditional lecture-based learning (LBL) on ophthalmology teaching were compared among students in a five-year programme. The questionnaire surveys of the students were collected and statistically analysed after the class. The final examination scores, including on elementary knowledge and case analysis, in the two groups were analysed. RESULTS: There were no statistically significant differences between the teachers and students in the baseline data. More students agreed that the BOPPPS-CBL model helped develop their problem-solving skills, analytical skills and motivation for learning better than the LBL model. There was no significant difference in learning pressure between the two groups. The final examination scores of the BOPPPS-CBL group were significantly higher than those of the LBL group. The overall course satisfaction of the BOPPPS-CBL group was obviously higher than that of the LBL group. CONCLUSIONS: The BOPPPS-CBL model is an effective ophthalmology teaching method for five-year paediatric undergraduates.

Downregulation of miR-211-5p Promotes Carboplatin Resistance in Human Retinoblastoma Y79 Cells by Affecting the GDNF-LIF Interaction.

Purpose: To investigate the role of the miR-211-5p-GDNF signaling pathway in carboplatin resistance of retinoblastoma Y79 cells and what factors it may be affected by. Methods: A carboplatin-resistant retinoblastoma cell line (Y79R) was established in vitro. RNA-seq and microRNA-seq were constructed between Y79 and Y79R cells. RNA interference, RT-PCR, Western blot (WB), and flow cytometry were used to verify the expression of genes and proteins between the two cell lines. The TargetScan database was used to predict the microRNAs that regulate the target genes. STING sites and Co-Immunoprecipitation (COIP) were used to study protein-protein interactions. Results: GDNF was speculated to be the top changed gene in the drug resistance in Y79R cell lines. Moreover, the speculation was verified by subsequent RT-PCR and WB results. When the expression of GDNF was knocked down, the IC50 of the Y79R cell line significantly reduced. GDNF was found to be the target gene of miR-211-5p. Downregulation of miR-211-5p promotes carboplatin resistance in human retinoblastoma Y79 cells. MiR-211-5p can regulate the expression of GDNF. Our further research also found that GDNF can bind to LIF which is also a secreted protein. Conclusion: Our results suggest that downregulation of miR-211-5p promotes carboplatin resistance in human retinoblastoma Y79 cells, and this process can be affected by GDNF-LIF interaction. These results can provide evidence for the reversal of drug resistance of RB.

Significant loss of soil inorganic carbon at the continental scale.

Widespread soil acidification due to atmospheric acid deposition and agricultural fertilization may greatly accelerate soil carbonate dissolution and CO2 release. However, to date, few studies have addressed these processes. Here, we use meta-analysis and nationwide-survey datasets to investigate changes in soil inorganic carbon (SIC) stocks in China. We observe an overall decrease in SIC stocks in topsoil (0-30 cm) (11.33 g C m-2 yr-1) from the 1980s to the 2010s. Total SIC stocks have decreased by ∼8.99 ± 2.24% (1.37 ± 0.37 Pg C). The average SIC losses across China (0.046 Pg C yr-1) and in cropland (0.016 Pg C yr-1) account for ∼17.6%-24.0% of the terrestrial C sink and 57.1% of the soil organic carbon sink in cropland, respectively. Nitrogen deposition and climate change have profound influences on SIC cycling. We estimate that ∼19.12%-19.47% of SIC stocks will be further lost by 2100. The consumption of SIC may offset a large portion of global efforts aimed at ecosystem carbon sequestration, which emphasizes the importance of achieving a better understanding of the indirect coupling mechanisms of nitrogen and carbon cycling and of effective countermeasures to minimize SIC loss.

Exosome-Mediated miR-4792 Transfer Promotes Bladder Cancer Cell Proliferation via Enhanced FOXC1/c-Myc Signaling and Warburg Effect.

Bladder cancer is the second-most common malignancy in the urogenital system and the most common in men. However, our understanding of the driving mechanisms of bladder cancer remains incomplete. The forkhead box (FOX) family of transcription factors is implicated in urogenital development and bladder malignancies. Many exosomal microRNAs have been identified as regulators and mediators of the expression of FOX, including the expression of FOXC1. miR-4792 has been known as a tumor miRNA suppressor. However, the function of miR-4792/FOXC1 signaling in bladder cancer development remains unknown. Here, we studied the role of miR-4792/FOXC1 signaling in bladder cancer by using multiple bladder cancer cell lines and bladder cancer mouse models through in vitro and in vivo approaches. We showed that FOXC1 is highly expressed in multiple bladder cancer cell lines and bladder tumor tissues. The knockdown of FOXC1 expression in bladder cancer cell lines decreases c-Myc expression levels, retards cell growth, and reduces aerobic glycolysis (also known as the Warburg effect) and lactic acid content. By contrast, the overexpression of FOXC1 elicits the opposite effects. FOXC1-downregulated bladder cancer cells form significantly smaller tumors in vivo. The inhibition of c-Myc reverses the effects of FOXC1 overexpression and leads to reduced cell proliferation, aerobic glycolysis, and lactic acid content. miR-4792 expression is downregulated in bladder tumor tissues. miR-4792 exposure to bladder cancer cells reduces the expression levels of FOXC1 and c-Myc, slows down cell growth, and decreases aerobic glycolysis and lactic acid content. However, the enhanced miR-4792 expression elicits opposite effects. These findings provided the first evidence that the exosome-mediated delivery of miR-4792 could play an important role in bladder cancer development through the downregulation of FOXC1 and c-Myc, which further inhibited aerobic glycolysis and lactic acid content.

Moderately decreasing fertilizer in fields does not reduce populations of cereal aphids but maximizes fitness of parasitoids.

Examination of the tradeoff between the extent of decreasing nitrogen input and pest suppression is crucial for maintaining the balance between essential yield and an efficient, sustainable pest control strategy. In this study, an experiment with four manipulated nitrogen fertilizer levels (70, 140, 210, and 280 kg N ha-1 = conventional level) was conducted to explore the effects of decreasing nitrogen on cereal aphids (Sitobion avenae and Rhopalosiphum padi) (Hemiptera: Aphididae), Aphidiinae parasitoids (Hymenoptera: Braconidae: Aphidiinae), and body sizes of parasitoids. The results indicated that nitrogen application, in the range of 70-280 kg N ha-1, has the potential to impact the populations of cereal aphids and their parasitoids. However, both differences between densities of cereal aphids and their parasitoids in moderate (140-210 kg N ha-1) and those in high nitrogen input (280 kg N ha-1) were not significant, and the parasitism rate was also unaffected. A higher parasitism rate reduced population growth of the cereal aphid (S. avenae). Additionally, a moderate decrease of nitrogen fertilizer from 280 to 140-210 kg N ha-1 maximized the body sizes of Aphidiinae parasitoids, indicating that a moderate decrease of nitrogen fertilizer could facilitate biocontrol of cereal aphid by parasitoids in the near future. We conclude that a moderate decrease in nitrogen application, from 280 to 140-210 kg N ha-1, does not quantitatively impact the densities of cereal aphids or the parasitism rate but can qualitatively maximize the fitness of the parasitoids.

Influence of Vitamin A deficiency on the transcriptomic profile of rat meibomian glands.

PURPOSE: Vitamin A deficiency (VAD) is associated with chalazion in young children. However, the underlying molecular mechanism remains unclear. In the present study, transcriptome data from rat meibomian glands (MGs) were analyzed to reveal specific molecular responses to VAD. METHODS: Total RNA was extracted and purified for library preparation and transcriptome sequencing. Differentially expressed genes (DEGs) between vitamin A normal (VAN) and VAD rats were analyzed using DESeq software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of DEGs were performed using the GO seq R package and KOBAS software. Real-time quantitative reverse transcription polymerase chain reaction was used to validate the RNA sequencing results. RESULTS: The number of DEGs in the VAD group compared to the VAN group was 3129 (1531 upregulated and 1598 downregulated) in the rat MGs. VAD upregulated a large number of lipid metabolism-related genes. GO analysis showed that the most enriched and meaningful terms were related to lipid metabolism (e.g., "oxidation-reduction process, GO: 0,055,114," "lipid metabolic process, GO: 000,662"). KEGG pathway analysis showed that most of the enriched signaling pathways were involved in lipid metabolism, including the PPAR signaling pathway associated with retinoic acid (RA)-mediated nuclear receptors. CONCLUSION: These findings demonstrate that VAD regulates the expression of numerous genes in the rat MG and that many of these genes are involved in lipid metabolic pathways.

Solution Processed Hybrid Polymer: HgTe Quantum Dot Phototransistor with High Sensitivity and Fast Infrared Response up to 2400 nm at Room Temperature.

Narrow bandgap semiconductor-based photodetectors often suffer from high room-temperature noise and are therefore operated at low temperatures. Here, a hybrid poly(3-hexylthiophene) (P3HT): HgTe quantum dot (QD) phototransistor is reported, which exhibits high sensitivity and fast photodetection up to 2400 nm wavelength range at room temperature. The active layer of the phototransistor consists of HgTe QDs well dispersed in a P3HT matrix. Fourier-transform infrared spectra confirm that chemical grafting between P3HT and HgTe QDs is realized after undergoing prolonged coblend stirring and a ligand exchange process. Thanks to the shifting of the charge transport into the P3HT and the partial passivation of the surface traps of HgTe QDs in the blend, the P3HT: HgTe QD hybrid phototransistor shows significantly improved gate-voltage tuning, 15 times faster response, and ≈80% reduction in the noise level compared to a pristine HgTe QD control device. More than 1011 Jones specific detectivity (estimated from the noise spectral density measured at 1 kHz) is achieved at room temperature, and the response time (measured at 22 mW cm-2 illumination intensity) of the device is less than 1.5 µs. That is comparable to commercial epitaxially grown IR photodetectors operated in the same wavelength range.

Refractive status and optical components of premature babies with or without retinopathy of prematurity at 7 years old.

BACKGROUND: This study aimed to investigate the refractive status and optical components of premature babies with or without retinopathy of prematurity (ROP) at 7 years old and to explore the influence of prematurity and ROP on the refractive status and optical components. METHODS: From January 2009 to February 2011, premature babies receiving fundus photographic screening (FPS) were recruited and divided into non-ROP group and ROP group. Full-term babies matched in age were recruited as controls. Auto-refractometer was employed to detect the corneal refractive power, corneal radius (CR) of curvature and corneal astigmatism, A-scan ultrasonography was performed to detect the anterior chamber depth (ACD), lens thickness (LT), vitreous thickness (VITR) and ocular axial length (AL), and retinoscopy was done following cycloplegia with 1% cyclopentolate in these babies at 7 years old. These parameters were compared among groups, and the correlations of gestational age and birth weight with the refractive status and optical components were further evaluated. RESULTS: Of 126 subjects, a total of 252 eyes were evaluated in this study, including 50 eyes of 25 subjects in ROP group (pre-threshold stage 1-3), 110 eyes of 55 subjects in non-ROP group and 92 eyes of 46 subjects in control group. The incidence of myopia was the highest in ROP group (9/50, 18%), followed by non-ROP group (11/110; 10%) and control group (6/92; 6.52%). The incidence of hyperopia was the highest in control group (21/92; 22.83%), followed by ROP group (8/50; 16%) and non-ROP group (10/110; 9.09%). The incidence of astigmatism was the highest in ROP group (18/50; 36%), followed by non-ROP group (25/110; 22.73%) and control group (12/92; 13.04%). The corneal astigmatism (-1.58, -1.11, -0.86 DC, P<0.01) and the mean degree of astigmatism (1.38, 1.17, 0.64 DC, P<0.05) in ROP group and non-ROP group were significantly higher than those in control group. The corneal refractive power in ROP group was more potent as compared to non-ROP group and control group (43.98, 43.16, 42.99 D, P<0.05); the corneal curvature in ROP group was significantly higher than that in non-ROP group and control group (7.87, 7.71, 7.67 mm, P<0.05); the ocular AL in ROP group and non-ROP group was significantly shorter than that in control group (2.41, 22.47, 22.78 mm, P<0.05). The LT in ROP group and non-ROP group was markedly thicker than that in control group (4.48, 4.45, 4.37 mm, P>0.05); the ACD in ROP group and non-ROP group was markedly deeper than in control group (3.16, 3.12, 3.21 mm, P>0.05). The gestational age was negatively related to corneal astigmatism (r=-0.208, P=0.013) and astigmatism (r=-0.226, P=0.004), but positively associated with ocular AL (r=0.252, P=0.005). The birth weight was negatively associated with corneal astigmatism (r=-0.30, P<0.001), astigmatism (r=-0.267, P=0.001), corneal refractive power (r=-0.255, P=0.001) and corneal curvature (r=0.242, P=0.001), but positively to ocular AL (r=0.243, P=0.001) and spherical equivalent refraction (SER) (r=0.151, P=0.028). CONCLUSIONS: (I) Premature babies with or without ROP are susceptible to myopia and astigmatism; (II) low birth weight, prematurity and ROP synergistically influence the development of refractive status and optical components, resulting in myopia and astigmatism; (III) premature babies with or without ROP have increased corneal curvature and LT, which are related to the higher incidence of myopia and astigmatism.

Association between allergic conjunctivitis and provisional tic disorder in children.

BACKGROUND: Allergic diseases are associated with a higher risk of Tourette's syndrome (TS). Provisional tic disorder (PTD) and eye blinking are often reported as the initial symptoms both in TS and in allergic conjunctivitis (AC). OBJECTIVE: To investigate the association between AC and PTD in children of 4-10 years of age in southwest China. METHODS: This case-control study was carried out at the Children's Hospital of Chongqing Medical University between January 2016 and June 2017. Age- and gender-matched children without PTD were included as the control group. Intraocular pressure was measured by non-contact tonometry, tear film break-up time by slit-lamp examination, and allergens by skin prick test (SPT). Multivariable logistic regression analysis was applied to adjust for the simultaneous effects of AC, dry eye, and allergic history in children with PTD. RESULTS: The frequency of AC was higher in the PTD group (74.3%, 52/70) than in the control group (17.1%, 12/70) (P < 0.001). The frequencies of positive SPT were found to be higher in the PTD group (80.0%, 56/70) than in the control group (20.0%, 14/70). AC, dry eye, and history of allergic rhinitis were significantly associated with PTD. CONCLUSION: The frequencies of AC are high in children with PTD. AC and dry eye may be both associated with PTD in children.

Risk Factors of Nosocomial Infection for Infants in Neonatal Intensive Care Units: A Systematic Review and Meta-Analysis.

BACKGROUND The aim of this study was to identify the nosocomial infection (NI) risk factors in neonatal Intensive Care Units (NICU). MATERIAL AND METHODS Databases (PubMed, Embase, Cochrane, VANFUN, CNKI, and VTTMS) were searched using index words to find relevant studies published before November 2018. Meta-analyses of relative risk (RR) were performed for the identification of risk factors. RESULTS Data from 22 cohort studies (2270 infants with and 21 605 infants without NI) were included in the meta-analysis. Infant weight of <2500 g (RR: 3.44, 95% CI: 2.31-5.11), gestational age of <37 weeks (RR: 3.85, 95% CI: 1.87-7.92), mechanical ventilation use (RR: 3.16, 95% CI: 2.21-4.50), venipuncture (RR: 3.01, 95% CI: 1.20-7.57), the incidence of asphyxia (RR: 1.68, 95% CI: 1.04-2.71), and feeding intolerance (RR: 2.12, 95% CI: 1.60-2.81) were identified as the risk factors for the incidence of NI. There was no significant publication bias. CONCLUSIONS This study shows that <2500 g infant body weight, gestational age of <37 weeks, mechanical ventilation utility, venipuncture, asphyxia incidence, and feeding intolerance are the risk factors for NI nosocomial infection in infants in NICU. Appropriate preventive measures and targeted interventions are needed.

Identification of Biomarkers Related to Neuropathic Pain Induced by Peripheral Nerve Injury.

Our study aimed to explore the molecular mechanisms and novel target genes of neuropathic pain via bioinformatics analysis. Gene expression profiling of GSE30691 which was consisted of sciatic nerve lesion and sham control samples at 3 days, 7 days, 21 days, and 40 days (D3, D7, D21, and D40) after injury were downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs) were identified for all the four time points. Overlapped DEGs for all the four time points were used for functional and weighted co-expression modular analysis. Afterwards, protein-protein interaction (PPI) network was analyzed by MCODE (Molecular Complex Detection) and BiNGO. Pathway network was constructed according to the enriched pathways of PPI network and relevant pathways selected from the Comparative Toxicogenomics Database. There were 355 overlapped DEGs for all the four time points. Two co-expression modules had significant positive correlations with disease. The top ten hub DEGs in the PPI network were Fos, Tp53, Csk, Map2k2, Stat3, Ccl2, Pxn, Tgfb1, Notch1, and Prkacb. Fos, Dusp1, Tp53, Tgfb1, and Map2k2 participated in MAPK signaling pathway, while Csk participated in chemokine signaling pathway. The expressions of Fos, Tp53, Csk, and Map2k2 were significantly increased at D3. Tp53, Csk, and Map2k2 continued overexpressing until at D7, and an elevated tendency in Csk expression could be observed until at D21. The expression of Fos reached up to the highest at D40. Fos, Tp53, Csk, and Map2k2 might be the potential biomarkers related to neuropathic pain.

Long noncoding RNA SNHG7 inhibits high glucose-induced human retinal endothelial cells angiogenesis by regulating miR-543/SIRT1 axis.

Diabetic retinopathy (DR) is the serious complication of type 2 diabetes mellitus, which could lead to visual impairment. Growing evidence have revealed the involvement of long non-coding RNAs (lncRNAs) in the pathogenesis of DR. Thus, this study was performed to investigate the role of lncRNA SNHG7 (small nucleolar RNA host gene 7) in high glucose (HG)-induced proliferation, migration, and angiogenesis of human retinal endothelial cells (hRECs). We discovered that SNHG7 was decreased in hRECs under HG stimuli. Although SNHG7 had no influence on cell viability, migration and angiogenesis under condition, overexpression of SNHG7 inhibited the HG-induced cell proliferation, migration and angiogenesis, as well as vascular endothelial growth factor (VEGF) expression in HG condition. In terms of mechanism, we found that SNHG7 directly inhibited miR-543, which targeted the 3'-UTR of Silent information regulator T1 (SIRT1) mRNA and subsequently downregulated the VEGF expression in hRECs. Ultimately, upregulation of miR-543 or inhibition of SIRT1 both abrogated the effect of SNHG7 on HG-induced angiogenesis. Collectively, our results suggested that SNHG7 is a potential molecular target for attenuating HG-induced angiogenesis in the DR through regulation of the miR-543-mediated SIRT1/VEGF pathway.

The antitumor function of arctigenin in human retinoblastoma cells is mediated by jagged­1.

Retinoblastoma is an intraocular malignant tumor that may severely affect vision and represents a life­threatening disease in children. Arctigenin (ATG) is an active compound that exhibits numerous pharmacological activities, which is isolated from the seeds of greater burdock (Arctium lappa Linnaeus), a plant used in traditional Chinese herbal medicine. The present study aimed to investigate the effects of ATG on cancer progression by analyzing the retinoblastoma cell line Y79. ATG exhibited a significant inhibitory effect on the viability of Y79 cells in a dose­dependent manner. Furthermore, treatment with ATG promoted apoptosis, and increased the protein expression levels of B­cell lymphoma 2 (BCL­2)­associated X protein and decreased the protein expression levels of BCL­2. Cell migration was suppressed following treatment with ATG, as assessed by Transwell migration assay. Furthermore, the protein expression levels of jagged­1 (JAG1) were decreased, and various factors involved in the Notch signaling pathway, including the Notch intracellular domain (NICD), transcription factor HES (HES)5 and HES1 were downregulated following treatment with ATG. The decreased expression levels of JAG1 were restored in response to JAG1 overexpression, alongside increases in the protein expression levels of NICD, HES5 and HES1. Furthermore, overexpression of JAG1 partly restored the cell viability and migration suppressed following treatment with ATG. In addition, ATG­induced apoptosis was reduced by JAG1 overexpression. Collectively, the present results suggested that ATG may serve as an antitumor compound by suppressing the proliferation and migration of retinoblastoma cells, inducing apoptosis, downregulating the protein expression levels of JAG1, and decreasing the activity of the Notch signaling pathway.

MXene-supported Co3O4 quantum dots for superior lithium storage and oxygen evolution activities.

A novel hybrid, composed of Co3O4 quantum dots supported on Ti3C2Tx (MXene) nanosheets, exhibits a strong synergetic effect, and shows superior lithium storage (capacity = 766.5 mA h g-1 at 2 A g-1 after 400 cycles) and oxygen evolution (overpotential = 340 mV at 10 mA cm-2) activities.

Metal-organic framework derived hollow porous CuO-CuCo2O4 dodecahedrons as a cathode catalyst for Li-O2 batteries.

Herein, hollow porous CuO-CuCo2O4 dodecahedrons are synthesized by using a simple self-sacrificial metal-organic framework (MOF) template, which resulted in dodecahedron morphology with hierarchically porous architecture. When evaluated as a cathodic electrocatalyst in lithium-oxygen batteries, the CuO-CuCo2O4 composite exhibits a significantly enhanced electrochemical performance, delivering an initial capacity of 6844 mA h g-1 with a remarkably decreased discharge/charge overpotential to 1.15 V (vs. Li/Li+) at a current density of 100 mA g-1 and showing excellent cyclic stability up to 111 charge/discharge cycles under a cut-off capacity of 1000 mA h g-1 at 400 mA g-1. The outstanding electrochemical performance of CuO-CuCo2O4 composite can be owing to the intrinsic catalytic activity, unique porous structure and the presence of substantial electrocatalytic sites. The ex situ XRD and SEM are also carried out to reveal the charge/discharge behavior and demonstrate the excellent reversibility of the CuO-CuCo2O4 based electrode.