Antiviral activity of luteolin against porcine epidemic diarrhea virus in silico and in vitro.

BACKGROUND: Porcine epidemic diarrhea virus (PEDV) mainly causes acute and severe porcine epidemic diarrhea (PED), and is highly fatal in neonatal piglets. No reliable therapeutics against the infection exist, which poses a major global health issue for piglets. Luteolin is a flavonoid with anti-viral activity toward several viruses. RESULTS: We evaluated anti-viral effects of luteolin in PEDV-infected Vero and IPEC-J2 cells, and identified IC50 values of 23.87 µM and 68.5 µM, respectively. And found PEDV internalization, replication and release were significantly reduced upon luteolin treatment. As luteolin could bind to human ACE2 and SARS-CoV-2 main protease (Mpro) to contribute viral entry, we first identified that luteolin shares the same core binding site on pACE2 with PEDV-S by molecular docking and exhibited positive pACE2 binding with an affinity constant of 71.6 µM at dose-dependent increases by surface plasmon resonance (SPR) assay. However, pACE2 was incapable of binding to PEDV-S1. Therefore, luteolin inhibited PEDV internalization independent of PEDV-S binding to pACE2. Moreover, luteolin was firmly embedded in the groove of active pocket of Mpro in a three-dimensional docking model, and fluorescence resonance energy transfer (FRET) assays confirmed that luteolin inhibited PEDV Mpro activity. In addition, we also observed PEDV-induced pro-inflammatory cytokine inhibition and Nrf2-induced HO-1 expression. Finally, a drug resistant mutant was isolated after 10 cell culture passages concomitant with increasing luteolin concentrations, with reduced PEDV susceptibility to luteolin identified at passage 10. CONCLUSIONS: Our results push forward that anti-PEDV mechanisms and resistant-PEDV properties for luteolin, which may be used to combat PED.

α-MSH ameliorates corneal surface dysfunction in scopolamine-induced dry eye rats and human corneal epithelial cells via enhancing EGFR expression.

Dry eye (DE) is a chronic, multifactorial ocular surface disease associated with visual disturbance, tear film instability, hyperosmolarity, ocular surface inflammation and damage. Effective intervention is necessary to control this disease. In this study we topically applied α-melanocyte stimulating hormone (α-MSH) on the ocular surface of scopolamine-induced DE rats and found that it promoted tear secretion, reduced tear breakup time and fluorescein sodium staining and increased the number of conjunctival goblet cells. To investigate the mechanism, protein array was conducted, which showed that α-MSH exerted its effects via epithelial growth factor receptor (EGFR) in the JAK-STAT signaling pathway. Furthermore, in vitro experiments showed that α-MSH protected human corneal epithelial cells (hCECs) by maintaining their migration ability and viability and decreasing apoptosis. However, blockade of EGFR abolished these protective effects. Moreover, α-MSH decreased the level of autophagy in benzalkonium chloride (BAC)-stressed hCECs via EGFR. These results demonstrated that α-MSH ameliorated lesions and restored ocular surface functions by upregulating EGFR expression.

School-based epidemiology study of myopia in Tianjin, China.

PURPOSE: To study the epidemiology of myopia in school-aged children in Tianjin and the relationship between visual acuity-based screening and refraction-based screening. METHOD: This school-based prospective cohort study was performed on children from 42 elementary schools and 17 middle schools in Tianjin, China. Totally 14,551 children, ages ranging from 5 to 16 years, were included in this study. Uncorrected visual acuity (UCVA) was determined by logarithmic tumbling E chart. Non-cycloplegic photorefraction was examined by the Spot (v2.1.4) photoscreener. The relationship between the UCVA and refractive error was investigated for different age groups. RESULTS: The overall prevalence of myopia at this school based screen is 78.2%, ranged from 10% at age of 5 to 95% at age of 16. The most dramatic increase in prevalence is from age of 6 (14.8%) to age of 7 (38.5%). The overall prevalence of high myopia is 2.5%. UCVA is found corresponding to spherical equivalent refraction (SER) in a manner of normal distribution and is significantly affected by age. When using UCVA to estimate the prevalence of myopia, the overall sensitivity and specificity are 0.824 and 0.820, respectively. Age-dependent optimal cutoff points and 95% confident intervals of such estimation are reported. CONCLUSIONS: Myopia is heavily affecting school-aged children in Tianjin, China. The refraction screening is preferable for myopia screening, whereas the UCVA screening results need to be interpreted in an age-dependent manner for myopia estimation.

The effects of local administration of mesenchymal stem cells on rat corneal allograft rejection.

BACKGROUND: Mesenchymal stem cells (MSCs) have been reported to promote long-term cellular and organ transplant acceptance due to their immunotherapeutic characteristics. Previous work from our lab using a rat allograft model has shown that systemic infusion of MSCs inhibited corneal allograft rejection and prolonged graft survival. Here, we further investigated the effects of local MSCs administration in the same animal model. METHODS: Donor-derived MSCs were isolated and cultured while corneal grafts obtained from Wistar rats were transplanted into Lewis rat hosts. Hosts were then randomly separated into four groups and treated with previously cultured MSCs at different times and doses. Graft survival was clinically assessed using slit-lamp biomicroscopy and the median survival time (MST) was calculated. Grafts were examined histologically using hematoxylin-eosin (H-E) staining and immunohistochemically using antibodies against CD4. A comprehensive graft analysis of IL-2, IL-4, IL-10, and IFN-γ expression was also conducted using both real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). RESULTS: Postoperative MSCs injection prolonged graft survival time when compared with controls (MST 9.8 ± 1.2 days). Injection twice of MSCs (MST 12.6 ± 1.4 days) was more effective than a single injection (MST 10.8 ± 1.3 days). MSCs-treated groups also showed suppression of inflammatory cell as well as CD4 + T cell infiltration in the allograft region. IL-4 and IL-10 levels were significantly increased in grafts obtained from postoperative twice MSCs-treated rats when compared with controls. There were no significant differences in IL-2 or IFN-γ expression across groups. CONCLUSIONS: Subconjunctival injection of MSCs in rats was effective in prolonging corneal allograft survival. This effect was mediated by inhibition of inflammatory and immune responses, indicating an anti-inflammatory shift in the balance of T helper (Th)1 to T helper(Th) 2.

Precursor Routes to Complex Ternary Intermetallics: Single-Crystal and Microcrystalline Preparation of Clathrate-I Na8Al8Si38 from NaSi + NaAlSi.

Single crystals of the ternary clathrate-I Na8Al8Si38 were synthesized by kinetically controlled thermal decomposition (KCTD), and microcrystalline Na8Al8Si38 was synthesized by spark plasma sintering (SPS) using a NaSi + NaAlSi mixture as the precursor. Na8AlxSi46-x compositions with x ≤ 8 were also synthesized by SPS from precursor mixtures of different ratios. The crystal structure of Na8Al8Si38 was investigated using both Rietveld and single-crystal refinements. Temperature-dependent transport and UV/vis measurements were employed in the characterization of Na8Al8Si38, with diffuse-reflectance measurement indicating an indirect optical gap of 0.64 eV. Our results indicate that, when more than one precursor is used, both SPS and KCTD are effective methods for the synthesis of multinary inorganic phases that are not easily accessible by traditional solid-state synthesis or crystal growth techniques.

Inflammatory bowel disease and risk for hemorrhoids: a Mendelian randomization analysis.

Observational studies have reported an association between inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), and hemorrhoids (HEM). However, the presence of a causal relationship within this observed association remains to be confirmed. Consequently, we utilized the Mendelian randomization (MR) method to assess the causal effects of IBD on hemorrhoids. We validated the association between IBD and hemorrhoids in humans based on genome-wide association studies (GWAS) data. To investigate the causal relationship between IBD and hemorrhoids, we performed a two-sample Mendelian randomization study using training and validation sets. The genetic variation data for IBD, CD, UC, and hemorrhoids were derived from published genome-wide association studies (GWAS) of individuals of European. Two-sample Mendelian randomization and Multivariable Mendelian randomization (MVMR) were employed to determine the causal relationship between IBD (CD or UC) and hemorrhoids. Genetically predicted overall IBD was positively associated with hemorrhoids risk, with ORs of 1.02 (95% CIs 1.01-1.03, P = 4.39 × 10-4) and 1.02 (95% CIs 1.01-1.03, P = 4.99 × 10-5) in the training and validation sets, respectively. Furthermore, we found that CD was positively associated with hemorrhoids risk, with ORs of 1.02 (95% CIs 1.01-1.03, P = 4.12 × 10-6) and 1.02 (95% CIs 1.01-1.02, P = 3.78 × 10-5) for CD in the training and validation sets, respectively. In addition, we found that UC in the training set was positively associated with hemorrhoids risk (ORs 1.02, 95% CIs 1.01-1.03, P = 4.65 × 10-3), while no significant causal relationship between UC and hemorrhoids was shown in the validation set (P > 0.05). However, after MVMR adjustment, UC in the training set was not associated with an increased risk of hemorrhoids. Our study showed that there is a causal relationship between CD and hemorrhoids, which may suggest that clinicians need to prevent the occurrence of hemorrhoids in CD patients.

Causal relationship between obesity and anorectal abscess: a Mendelian randomization study.

Background: Observational studies have indicated that obesity is a risk factor for anorectal abscess (ARB). However, it remains unclear whether a causal genetic relationship exists between obesity and ARB. Methods: Univariate and multivariate Mendelian randomization (MR) were conducted using data from a large, published genome-wide association study (GWAS) of European ancestry to infer a causal relationship between obesity and ARB. Inverse variance weighted (IVW) analysis served as the primary analysis method, with results reported as odds ratios (OR). Results: MR analysis revealed that body mass index (BMI) positively affects ARB (OR 1.974, 95% confidence interval (CI) 1.548-2.519, p = 4.34 × 10-8). The weighted median method (OR = 1.879, 95% CI 1.248-2.829, p = 0.002) and Bayesian model averaging (BMA) (OR = 1.88, 95% CI 1.477-2.392, p = 2.85 × 10-7) also demonstrated consistent results. Subsequently, the impact of several obesity-related characteristics on ARB was assessed. Body fat percentage (BF), whole body fat mass (FM), waist circumference (WC), and hip circumference (HC) were found to be causally associated with an increased risk of ARB. However, these associations vanished after adjusting for BMI effects. Conclusion: The study confirms a positive causal effect of obesity on ARB, highlighting that reasonable weight control is an important strategy to reduce the incidence of ARB.

Exposure and Health Risk Assessment of Heavy Metal in Crayfish from the Middle and Lower Reaches of the Yangtze River.

Red swamp crayfish (Procambarus clarkia) is an exposed species to heavy metals due to their lifestyle of direct contact with sediments. Based on the complete crayfish industry, we focus on the presence of heavy metals in crayfish from different circulation links, which provides a new idea for the investigation of heavy metals in food. To analyze the exposure levels of heavy metals in crayfish during aquaculture and circulation, the five elements (Cd, Pb, Hg, Cr, Cu) in crayfish from 126 sampling sites were investigated. Cultured environmental samples were collected for Spearman correlation analysis. Monte Carlo simulation was used to analyze the uncertain health risks of heavy metals in crayfish. The results indicated that the average heavy metal concentrations in crayfish were all below the limit threshold values. The hepatopancreas was the main target organ for heavy metal accumulation (Cd: 0.3132 mg/kg; Pb: 0.0258 mg/kg; Hg: 0.0072 mg/kg; Cr: 0.1720 mg/kg; Cu: 10.6816 mg/kg). The positive correlation of heavy metal content between crayfish and sediments was not significant under the crayfish-rice coculture model. The 95th HI values for adults and children ranged from 0.022 to 0.042 and 0.071 to 0.137, well below 1, indicating that heavy metals do not pose a noncarcinogenic risk to humans. The potential carcinogenic risk of Cd and Cr in crayfish should be taken seriously, as the 95th CR values for children have reached 4.299 × 10-5 and 6.509 × 10-5, respectively.

Congenital epiblepharon in Chinese school-age children: a cross-sectional study.

PURPOSE: To investigate the prevalence and body mass index (BMI) associations of congenital lower epiblepharon in children in China and the difference in the refractive errors between children with and without epiblepharon. METHODS: Children 6-12 years of age in Beichen District of Tianjin were screened for congenital epiblepharon from September to October 2017. All children underwent slit-lamp examination, strabismus screening, visual acuity examination and refraction. Weight and height were also recorded. The prevalence of lower epiblepharon in school-age children was evaluated, and its association with age, sex, BMI, and refractive error was analyzed. RESULTS: A total of 28,225 children were examined; 564 had epiblepharon. The prevalence of epiblepharon was found to be, for 6-year-olds, 2.50%; for 7-year-olds, 2.13%; for 8-year-olds, 2.10%; for 9-year-olds, 1.97%; for 10-year-olds, 1.85%; for 11-year-olds, 1.67%; and for 12-year-olds, 1.19% (P < 0.05). The prevalence of overweight and obesity in children with epiblepharon was found to be 16.7% and 47.2%, respectively. The prevalence and degree of astigmatism was higher than in nonepiblepharon children. We found a possible association between severity of astigmatism and severity of epiblepharon. CONCLUSIONS: In our study, the prevalence of epiblepharon decreased with advancing age, and the majority of children with epiblepharon were found to be overweight or obese. Epiblepharon was associated with astigmatism.

Research on precise lithium battery state of charge estimation method based on CALSE-LSTM model and pelican algorithm.

This paper presents an innovative fusion model called "CALSE-LSTM," which integrates Convolutional Neural Networks (CNNs), Long Short-Term Memory Networks (LSTMs), self-attention mechanisms, and squeeze-and-excitation attention mechanisms to optimize the estimation accuracy of the State of Charge (SoC). The model incorporates battery historical data as input and employs a dual-attention mechanism based on CNN-LSTM to extract diverse features from the input data, thereby enhancing the model's ability to learn hidden information. To further improve model performance, we fine-tune the model parameters using the Pelican algorithm. Experiments conducted under Urban Dynamometer Driving Schedule (UDDS) conditions show that the CALSE-LSTM model achieves a Root Mean Squared Error (RMSE) of only 1.73 % in lithium battery SoC estimation, significantly better than GRU, LSTM, and CNN-LSTM models, reducing errors by 31.9 %, 31.3 %, and 15 %, respectively. Ablation experiments further confirm the effectiveness of the dual-attention mechanism and its potential to improve SoC estimation performance. Additionally, we validate the learning efficiency of CALSE-LSTM by comparing model training time with the number of iterations. Finally, in the comparative experiment with the Kalman filtering method, the model in this paper significantly improved its performance by incorporating power consumption as an additional feature input. This further verifies the accuracy of CALSE-LSTM in estimating the State of Charge (SoC) of lithium batteries.

Longitudinal Changes in Refractive Development in Highly Hyperopic Children: A 2.6-11.2 Year Follow-up of Preschoolers Diagnosed with High Hyperopia.

PURPOSE: This study aims to elucidate the longitudinal refractive and ocular biometric alterations in preschool children with high hyperopia who underwent early interventions. METHODS: We conducted a retrospective analysis of preschool children diagnosed with high hyperopia at Tianjin Medical University Eye Hospital between 2011 and 2023. Inclusion criteria required an initial examination with cycloplegic refraction, bilateral spherical equivalent power (SE) ≥ +5.00D with a difference <1.00D, a minimum two-year follow-up, and at least three ocular biometric measurements. The annual axial growth rate evaluated emmetropization in highly hyperopic children. We applied Restricted Cubic Spline (RCS) models to explore potential nonlinear relationships between age and spherical equivalent, axial length, corneal curvature, and axial length-to-corneal curvature ratio. Additionally, Mixed-effects models were employed to investigate factors associated with changes in refractive error and axial length. RESULTS: The study enrolled 60 eligible subjects, with a median initial diagnosis age of 3.5 years (IQR, 2.8-4.9 years) and a median last visit age of 9.3 years (IQR, 8.1-10.8 years). The average follow-up duration was 5.7 years. RCS analysis revealed notable nonlinear changes in spherical equivalent power, axial length, and axial length-to-corneal curvature ratio, although corneal curvature displayed no statistically significant nonlinear trend. Factors affecting SE changes included the presence of strabismus, the use of cycloplegia, baseline SE, and age. Conversely, changes in axial length solely correlated with baseline axial length and age. CONCLUSION: Highly hyperopic preschool children undergoing early intervention display a marked emmetropization tendency, though most still remain moderately to highly hyperopic, with the progression of refractive changes showing non-uniform patterns with respect to age.

High-Performance Detection of Mycobacterium bovis in Milk Using Recombinase-Aided Amplification-Clustered Regularly Interspaced Short Palindromic Repeat-Cas13a-Lateral Flow Detection.

Mycobacterium bovis (M. bovis), the microorganism responsible for bovine tuberculosis (bTB), is transferred to people by the ingestion of unpasteurized milk and unprocessed fermented milk products obtained from animals with the infection. The identification of M. bovis in milk samples is of the utmost importance to successfully prevent zoonotic diseases and maintain food safety. This study presents a comprehensive description of a highly efficient molecular test utilizing recombinase-aided amplification (RPA)-clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein (Cas) 13a-lateral flow detection (LFD) for M. bovis detection. In contrast to ELISA, RPA-CRISPR-Cas13a-LFD exhibited greater accuracy and sensitivity in the detection of M. bovis in milk, presenting a detection limit of 2 × 100 copies/µL within a 2 h time frame. The two tests exhibited a moderate level of agreement, as shown by a kappa value of 0.452 (95%CI: 0.287-0.617, p < 0.001). RPA-CRISPR-Cas13a-LFD holds significant potential as a robust platform for pathogen detection in complex samples, thereby enabling the more dependable regulation of food safety examination, epidemiology research, and medical diagnosis.

Intracranial EEG signals disentangle multi-areal neural dynamics of vicarious pain perception.

Empathy enables understanding and sharing of others' feelings. Human neuroimaging studies have identified critical brain regions supporting empathy for pain, including the anterior insula (AI), anterior cingulate (ACC), amygdala, and inferior frontal gyrus (IFG). However, to date, the precise spatio-temporal profiles of empathic neural responses and inter-regional communications remain elusive. Here, using intracranial electroencephalography, we investigated electrophysiological signatures of vicarious pain perception. Others' pain perception induced early increases in high-gamma activity in IFG, beta power increases in ACC, but decreased beta power in AI and amygdala. Vicarious pain perception also altered the beta-band-coordinated coupling between ACC, AI, and amygdala, as well as increased modulation of IFG high-gamma amplitudes by beta phases of amygdala/AI/ACC. We identified a necessary combination of neural features for decoding vicarious pain perception. These spatio-temporally specific regional activities and inter-regional interactions within the empathy network suggest a neurodynamic model of human pain empathy.

CRISPR-Cas9 screening identifies INTS3 as an anti-apoptotic RNA-binding protein and therapeutic target for colorectal cancer.

Growing evidences indicate that RNA-binding proteins (RBPs) play critical roles in regulating the RNA splicing, polyadenylation, stability, localization, translation, and turnover. Abnormal expression of RBPs can promote tumorigenesis. Here, we performed a CRISPR screen using an RBP pooled CRISPR knockout library and identified 27 potential RBPs with role in supporting colorectal cancer (CRC) survival. We found that the deletion/depletion of INTS3 triggered apoptosis in CRC. The in vitro experiments and RNA sequencing revealed that INTS3 destabilized pro-apoptotic gene transcripts and contributed to the survival of CRC cells. INTS3 loss delayed CRC cells growth in vivo. Furthermore, delivery of DOTAP/cholesterol-mshINTS3 nanoparticles inhibited CRC tumor growth. Collectively, our work highlights the role of INTS3 in supporting CRC survival and provides several novel therapeutic targets for treatment.

In silico and in vitro evaluation of antiviral activity of wogonin against main protease of porcine epidemic diarrhea virus.

The high mortality rate of weaned piglets infected with porcine epidemic diarrhea virus (PEDV) poses a serious threat to the pig industry worldwide, demanding urgent research efforts related to developing effective antiviral drugs to prevent and treat PEDV infection. Small molecules can possibly prevent the spread of infection by targeting specific vital components of the pathogen's genome. Main protease (Mpro, also named 3CL protease) plays essential roles in PEDV replication and has emerged as a promising target for the inhibition of PEDV. In this study, wogonin exhibited antiviral activity against a PEDV variant isolate, interacting with the PEDV particles and inhibiting the internalization, replication and release of PEDV. The molecular docking model indicated that wogonin was firmly embedded in the groove of the active pocket of Mpro. Furthermore, the interaction between wogonin and Mpro was validated in silico via microscale thermophoresis and surface plasmon resonance analyses. In addition, the results of a fluorescence resonance energy transfer (FRET) assay indicated that wogonin exerted an inhibitory effect on Mpro. These findings provide useful insights into the antiviral activities of wogonin, which could support future research into anti-PEDV drugs.`.

Evaluation and Follow-up of Myopia Prevalence Among School-Aged Children Subsequent to the COVID-19 Home Confinement in Feicheng, China.

Importance: Progression of myopia in a school-aged population due to home confinement (January to May 2021) during the COVID-19 pandemic has been previously reported. A key remaining question was whether the myopia spike in children aged 6 to 8 years persisted. Objective: To investigate the changes in refractive status and prevalence of myopia in school-aged children 1 year after home confinement ended in China. Design, Setting, and Participants: This cross-sectional study with a cohort substudy prospectively evaluated data from school-based photoscreening in Feicheng, China. Children aged 6 to 13 years participated in 8 screenings from 2015 to 2021. Exposures: Noncycloplegic photorefraction was conducted using the Spot Vision photoscreener. Main Outcomes and Measures: The main outcomes were the differences in spherical equivalent refraction (SER) and prevalence of myopia between 2020 (during home confinement) and 2021 (after home confinement). The SER was recorded for each child, and the prevalence of myopia was calculated annually for each age group. Results: A total of 325 443 children participated in the study (51.4% boys, 48.6% girls; age range, 6 to 13 years). Compared with 2020, the mean SER of children in 2021 increased significantly for those aged 6 (0.42 diopters [D]), 7 (0.41 D), and 8 (0.33 D) years. The prevalence of myopia in 2021 was similar to in 2019 for each age group (aged 6 years: 7.9% vs 5.7%; aged 7 years: 13.9% vs 13.6%; aged 8 years: 29.5% vs 26.2%). Both the prevalence of myopia and mean SER for these children returned to their prepandemic levels. Conclusions and Relevance: Compared with 2020, the prevalence of myopia among children aged 6 to 8 years in the 2021 screenings decreased, and the mean SER returned to prepandemic level. The refractive development in children aged 6 to 8 years may be most susceptible to environmental changes. These findings support the premise that age 6 to 8 years is a critical period for myopia development and suggest a need to focus preventive interventions for myopia control on children in this age range.

Genome-scale CRISPR screen identifies TRIM2 and SLC35A1 associated with porcine epidemic diarrhoea virus infection.

Porcine epidemic diarrhoea (PED) caused by the porcine epidemic diarrhoea virus (PEDV) is the most devastating disease in the global pig industry due to its high mortality rate in piglets. The host factors critical for PEDV replication are poorly understood. Here, we designed a pooled African green monkey genome-scale CRISPR/Cas9 knockout (VeroCKO) library containing 75,608 single guide RNAs targeting 18,993 protein-coding genes. Subsequently, we use the VeroCKO library to identify key host factors facilitating PEDV infection in Vero E6 cells. Several previously unreported genes associated with PEDV infection are highly enriched post-PEDV selection. We discovered that knocking out the tripartite motif 2 (TRIM2) and the solute carrier family 35 member A1 (SLC35A1) inhibited PEDV replication. Virtual screening and molecular docking approaches showed that chem-80,048,685 (M2) s ignificantly inhibited PEDV attachment and late replication by impeding SLC35A1. Furthermore, we found that knocking out SLC35A1 in Vero E6 cells upregulated a disintegrin and metalloprotease protein-17 (ADAM17) by splicing porcine aminopeptidase N (pAPN) and angiotensin-converting enzyme 2 (ACE2) ectodomains to reduce PEDV-infection in a CMP-Sialic Acid (CMP-SA) cell entry-independent manner. These findings provide a new perspective for a better understanding of host-pathogen interactions and new therapeutic targets for PEDV infection.

The influence of time structure on prediction motion in visual and auditory modalities.

Usually people can estimate the correct position of a moving object even when it temporarily moves behind an occlusion. Studies have been performed on this type of occluded motion with prediction motion (PM) tasks in the laboratory. Previous publications have emphasized that people could use mental imagery or apply an oculomotor system to estimate the arrival of a moving stimulus at the target place. Nevertheless, these two ways cannot account for the performance difference under a different set of conditions. Our study tested the role of time structure in a time-to-collision (TTC) task using visual and auditory modalities. In the visual condition, the moving red bar travelled from left to right and was invisible during the entire course but flashed at the initial and the occluded points. The auditory condition and visual condition were alike, except that the flashes in the visual condition were changed to clicks at the initial and the occluded points. The results illustrated that participants' performance was better in the equal time structure condition. The comparison between the two sense modalities demonstrated a similar tendency, which suggested there could be common cognitive processes between visual and auditory modalities when participants took advantage of temporal cues to judge TTC.

Screening and predicted value of potential biomarkers for breast cancer using bioinformatics analysis.

Breast cancer is the most common cancer and the leading cause of cancer-related deaths in women. Increasing molecular targets have been discovered for breast cancer prognosis and therapy. However, there is still an urgent need to identify new biomarkers. Therefore, we evaluated biomarkers that may aid the diagnosis and treatment of breast cancer. We searched three mRNA microarray datasets (GSE134359, GSE31448 and GSE42568) and identified differentially expressed genes (DEGs) by comparing tumor and non-tumor tissues using GEO2R. Functional and pathway enrichment analyses of the DEGs were performed using the DAVID database. The protein-protein interaction (PPI) network was plotted with STRING and visualized using Cytoscape. Module analysis of the PPI network was done using MCODE. The associations between the identified genes and overall survival (OS) were analyzed using an online Kaplan-Meier tool. The redundancy analysis was conducted by DepMap. Finally, we verified the screened HUB gene at the protein level. A total of 268 DEGs were identified, which were mostly enriched in cell division, cell proliferation, and signal transduction. The PPI network comprised 236 nodes and 2132 edges. Two significant modules were identified in the PPI network. Elevated expression of the genes Discs large-associated protein 5 (DLGAP5), aurora kinase A (AURKA), ubiquitin-conjugating enzyme E2 C (UBE2C), ribonucleotide reductase regulatory subunit M2(RRM2), kinesin family member 23(KIF23), kinesin family member 11(KIF11), non-structural maintenance of chromosome condensin 1 complex subunit G (NCAPG), ZW10 interactor (ZWINT), and denticleless E3 ubiquitin protein ligase homolog(DTL) are associated with poor OS of breast cancer patients. The enriched functions and pathways included cell cycle, oocyte meiosis and the p53 signaling pathway. The DEGs in breast cancer have the potential to become useful targets for the diagnosis and treatment of breast cancer.

Short, enantioselective, gram-scale synthesis of (-)-zephyranthine.

A reasonable synthesis design by strategically integrating functional group manipulation into the ring system construction resulted in a short, enantioselective, gram-scale total synthesis of (-)-zephyranthine. The concise route includes a catalytic Michael/Michael cascade for the asymmetric synthesis of a penta-substituted cyclohexane with three contiguous stereogenic centers, a remarkable 8-step one-pot operation to easily assemble the zephyranthine tetracyclic skeleton, the regioselective construction of a double bond in the C ring and an asymmetric dihydroxylation. This synthesis is also flexible and paves a potential path to a variety of cyclohexylamine-fused tricyclic or polycyclic alkaloids.