The combination of allicin with domiphen is effective against microbial biofilm formation.

Background: Microorganisms in biofilms are particularly difficult to control because of their increased survival and antibiotic resistance. Allicin and domiphen were employed to inhibit the microbial growth and biofilm formation of Staphylococcus aureus, Escherichia coli, and Candida albicans strains. Methods: Broth microdilution method and checkerboard assay were conducted to determine the efficacy of allicin combined with domiphen against S. aureus, E. coli, and C. albicans. Microbial biofilm formation was measured using the crystal violet staining method and fluorescence microscopy. And the total viable count of the biofilm cells on material surface after the treatment with antimicrobial reagents was calculated with the plate count technique. Results: The two drugs showed synergistic effects against the pathogens with a fractional bactericidal concentration of less than 0.38. The combination of 64 µg/mL allicin with 1 µg/mL domiphen dispersed over 50% of the biofilm mass of S. aureus, E. coli, and C. albicans. In addition, the drug combination reduced the total viable counts of E. coli and C. albicans biofilm cells on stainless steel and polyethylene surfaces by more than 102 CFU/mL. Conclusion: The combination of allicin and domiphen is an effective strategy for efficiently decreasing biofilms formation on various industrial materials surfaces.

Visual SLAM for Unmanned Aerial Vehicles: Localization and Perception.

Localization and perception play an important role as the basis of autonomous Unmanned Aerial Vehicle (UAV) applications, providing the internal state of movements and the external understanding of environments. Simultaneous Localization And Mapping (SLAM), one of the critical techniques for localization and perception, is facing technical upgrading, due to the development of embedded hardware, multi-sensor technology, and artificial intelligence. This survey aims at the development of visual SLAM and the basis of UAV applications. The solutions to critical problems for visual SLAM are shown by reviewing state-of-the-art and newly presented algorithms, providing the research progression and direction in three essential aspects: real-time performance, texture-less environments, and dynamic environments. Visual-inertial fusion and learning-based enhancement are discussed for UAV localization and perception to illustrate their role in UAV applications. Subsequently, the trend of UAV localization and perception is shown. The algorithm components, camera configuration, and data processing methods are also introduced to give comprehensive preliminaries. In this paper, we provide coverage of visual SLAM and its related technologies over the past decade, with a specific focus on their applications in autonomous UAV applications. We summarize the current research, reveal potential problems, and outline future trends from academic and engineering perspectives.

Deep learning-based accurate diagnosis and quantitative evaluation of microvascular invasion in hepatocellular carcinoma on whole-slide histopathology images.

BACKGROUND: Microvascular invasion (MVI) is an independent prognostic factor that is associated with early recurrence and poor survival after resection of hepatocellular carcinoma (HCC). However, the traditional pathology approach is relatively subjective, time-consuming, and heterogeneous in the diagnosis of MVI. The aim of this study was to develop a deep-learning model that could significantly improve the efficiency and accuracy of MVI diagnosis. MATERIALS AND METHODS: We collected H&E-stained slides from 753 patients with HCC at the First Affiliated Hospital of Zhejiang University. An external validation set with 358 patients was selected from The Cancer Genome Atlas database. The deep-learning model was trained by simulating the method used by pathologists to diagnose MVI. Model performance was evaluated with accuracy, precision, recall, F1 score, and the area under the receiver operating characteristic curve. RESULTS: We successfully developed a MVI artificial intelligence diagnostic model (MVI-AIDM) which achieved an accuracy of 94.25% in the independent external validation set. The MVI positive detection rate of MVI-AIDM was significantly higher than the results of pathologists. Visualization results demonstrated the recognition of micro MVIs that were difficult to differentiate by the traditional pathology. Additionally, the model provided automatic quantification of the number of cancer cells and spatial information regarding MVI. CONCLUSIONS: We developed a deep learning diagnostic model, which performed well and improved the efficiency and accuracy of MVI diagnosis. The model provided spatial information of MVI that was essential to accurately predict HCC recurrence after surgery.

A Richer Vocabulary of Chinese Personality Traits: Leveraging Word Embedding Technology for Mining Personality Descriptors.

This study uses a data-driven approach to mine the distribution of personality traits among Chinese people in the Chinese social context. Based on the hypothesis of personality lexicology, word embedding technology was employed in machine learning to mine personality vocabulary from Tencent's word embedding database. More than 10,000 Chinese personality descriptors were extracted and analyzed using Gaussian Mixture Model Cluster and Hierarchical clustering analysis. The data was collected from 658 Chinese people randomly from all parts of China through an online questionnaire method. The results reveal six personality traits in the Chinese context, expanding the personality thesaurus and providing examples to illustrate each trait. The findings coincide with previous research on the five-factor model, which partially describes the personality traits of Chinese people, but does not offer a complete explanation of their typical social behavior patterns. Additionally, the study supports the notion of cultural particularity in personality traits. The approach used in this study offers a richer personality vocabulary than traditional personality mining methods, and word embedding technology captures richer semantic information in Chinese. The six Chinese personality traits identified in this study will also be used to explore how to quantify and evaluate personality traits based on word embedding and personality descriptors.

Depression and coronary heart disease: mechanisms, interventions, and treatments.

Coronary heart disease (CHD), a cardiovascular condition that poses a significant threat to human health and life, has imposed a substantial economic burden on the world. However, in contrast to conventional risk factors, depression emerges as a novel and independent risk factor for CHD. This condition impacts the onset and progression of CHD and elevates the risk of adverse cardiovascular prognostic events in those already affected by CHD. As a result, depression has garnered increasing global attention. Despite this growing awareness, the specific mechanisms through which depression contributes to the development of CHD remain unclear. Existing research suggests that depression primarily influences the inflammatory response, Hypothalamic-pituitary-adrenocortical axis (HPA) and Autonomic Nervous System (ANS) dysfunction, platelet activation, endothelial dysfunction, lipid metabolism disorders, and genetics, all of which play pivotal roles in CHD development. Furthermore, the effectiveness and safety of antidepressant treatment in CHD patients with comorbid depression and its potential impact on the prognosis of CHD patients have become subjects of controversy. Further investigation is warranted to address these unresolved questions.

Non-Equilibrium Assembly of Atomically-Precise Copper Nanoclusters.

Accurate structure control in dissipative assemblies (DSAs) is vital for precise biological functions. However, accuracy and functionality of artificial DSAs are far from this objective. Herein, a novel approach is introduced by harnessing complex chemical reaction networks rooted in coordination chemistry to create atomically-precise copper nanoclusters (CuNCs), specifically Cu11(µ9-Cl)(µ3-Cl)3L6Cl (L = 4-methyl-piperazine-1-carbodithioate). Cu(I)-ligand ratio change and dynamic Cu(I)-Cu(I) metallophilic/coordination interactions enable the reorganization of CuNCs into metastable CuL2, finally converting into equilibrium [CuL·Y]Cl (Y = MeCN/H2O) via Cu(I) oxidation/reorganization and ligand exchange process. Upon adding ascorbic acid (AA), the system goes further dissipative cycles. It is observed that the encapsulated/bridging halide ions exert subtle influence on the optical properties of CuNCs and topological changes of polymeric networks when integrating CuNCs as crosslink sites. CuNCs duration/switch period could be controlled by varying the ions, AA concentration, O2 pressure and pH. Cu(I)-Cu(I) metallophilic and coordination interactions provide a versatile toolbox for designing delicate life-like materials, paving the way for DSAs with precise structures and functionalities. Furthermore, CuNCs can be employed as modular units within polymers for materials mechanics or functionalization studies.

Association between ambient air pollution exposure in pregnant women with antiphospholipid syndrome in Nanjing, China.

Antenatal exposure to air pollutants is thought to be associated with a variety of maternal blood markers as well as adverse birth outcomes. However, the dysgenic influence of air pollutants on the antiphospholipid syndrome (APS) in mothers and their pregnancy outcomes remains unclear. In the current study, 371 mother-infant pairs (189 healthy: 182 APS) from Nanjing Maternal and Child Health Hospital as well as air pollutants concentration from their living environment were used to investigate correlations between air pollution with maternal blood indicators and fetal birth weight in the groups of APS and healthy mothers. Generalized linear model was used to evaluate the contributions of air pollutant exposure during pregnancy to the blood indicators variation. The relationships between birth weight with specific air pollutant and blood index were analyzed using ridge regression. Results showed that APS fetal birth weight was significantly impacted by air pollutant exposure during pregnancy, in particular, the birth weight decreased significantly along with increasing fine particulate matter 2.5 (PM2.5) and fine particulate matter 10 (PM10) exposure concentrations throughout pregnancy. In contrast, birth weight increased significantly with sulfur dioxide (SO2) exposure. In addition, APS-related blood indicators comprised of platelet distribution width (PDW), total bilirubin (TBIL), mean platelet volume (MPV), platelet-larger cell ratio (P_LCR), homocysteine (HCY), alkaline phosphatase (ALP), direct bilirubin (DBIL), basophilic granulocyte (BAS), platelet thrombocytocrit (PCT), preprandial glucose levels (OGTT0), monocytes (MON), and monocytes ratio (MON_ratio) were also strongly related with prenatal exposure to PM2.5 and PM10, in which PDW levels showed most strongly negative impaction on fetal birth weight. Together, we showed that prenatal exposure to air pollutant (PM2.5 and PM10) may exacerbate the poor birth outcomes of low birth weight by impacting APS maternal blood indicators especially for PDW.

Enhanced toluene gas-sensing properties of MEMS sensor based on Pt-loaded SnO2nanoparticles.

Rapid detection of low concentration toluene is highly desirable in environment monitoring, industrial processes, medical diagnosis, etc. In this study, we prepared Pt-loaded SnO2monodispersed nanoparticles through hydrothermal method and assembled a sensor based on micro-electro-mechanical system (MEMS) to detect toluene. Compared with the pure SnO2, the 2.92 wt% Pt-loaded SnO2sensor exhibits a 2.75 times higher gas sensitivity to toluene at about 330 °C. Meanwhile, the 2.92 wt% Pt-loaded SnO2sensor also has a stable and good response to 100 ppb of toluene. Its theoretical detection limit is calculated as low as 12.6 ppb. Also, the sensor has a short response time of ∼10 s to different gas concentrations, as well as the excellent dynamic response-recovery characteristics, selectivity, and stability. The improved performance of Pt-loaded SnO2sensor can be explained by the increase of oxygen vacancies and chemisorbed oxygen species. The electronic and chemical sensitization of Pt to SnO2-based sensor, together with small size and fast gas diffusion of the MEMS design ensured fast response and ultra-low toluene detection. This provides new ideas and decent prospect for developing miniaturized, low-power-consumption, and portable application of gas sensing devices.

EphA4/ephrinA3 reverse signaling induced Müller cell gliosis and production of pro-inflammatory cytokines in experimental glaucoma.

Previous work showed that ephrinA3/EphA4 forward signaling contributed to retinal ganglion cell (RGC) damage in experimental glaucoma. Since up-regulated patterns of ephrinA3 and EphA4 were observed in Müller cells and RGCs, an EphA4/ephrinA3 reverse signaling may exist in Müller cells of chronic ocular hypertension (COH) retina. We investigated effects of EphA4/ephrinA3 reverse signaling activation on Müller cells in COH retina. Intravitreal injection of the ephrinA3 agonist EphA4-Fc increased glial fibrillary acidic protein (GFAP) levels in normal retinas, suggestive of Müller cell gliosis, which was confirmed in purified cultured Müller cells treated with EphA4-Fc. These effects were mediated by intracellular STAT3 signaling pathway as phosphorylated STAT3 (p-STAT3) levels and ratios of p-STAT3/STAT3 were significantly increased in both COH retinas and EphA4-Fc intravitreally injected retinas, as well as in EphA4-Fc treated purified cultured Müller cells. The increase of GFAP protein levels in EphA4-Fc-injected retinas and EphA4-Fc treated purified cultured Müller cells could be partially eliminated by stattic, a selective STAT3 blocker. Co-immunoprecipitation results testified to the presence of interaction between ephrinA3 and STAT3/p-STAT3. In addition, intravitreal injection of EphA4-Fc or EphA4-Fc treatment of cultured Müller cells significantly up-regulated mRNA and protein contents of pro-inflammatory cytokines. Moreover, intravitreal injection of EphA4-Fc increased the number of apoptotic RGCs, which could be reversed by the tyrosine kinase blocker PP2. Overall, EphA4/ephrinA3 reverse signaling may induce Müller cell gliosis and increases release of pro-inflammatory factors, which could contribute to RGC death in glaucoma. Inhibition of EphA4/ephrinA3 signaling may provide an effective neuroprotection in glaucoma.

Different characteristics of striatal resting-state functional conectivity in treatment-resistant and non-treatment-resistant depression.

Major depressive disorder is associated with a reward deficit manifested by abnormal striatal function. However, differences between treatment-resistant depression (TRD) and non TRD (nTRD) in striatal whole-brain functional connectivity (FC) have not been elucidated. Thirty-eight patients with TRD, 42 patients with nTRD, and 39 healthy controls (HCs) were recruited for this study. A seed-based FC approach was used to analyze abnormalities in six predefined striatal subregion circuits in the three groups of subjects, and further explore the correlation between abnormal FC and clinical symptoms. Results revealed that compared with the nTRD group, the TRD group showed increased FC of the inferior ventral striatum with the bilateral orbital area of the middle frontal gyrus, right cerebellum posterior lobe, left parahippocampal gyrus, left middle occipital gyrus and left lingual gyrus. Compared with the HC group, the TRD group showed a wider range of altered striatal function than the nTRD group. In the TRD group, the HAMD-17 scores were positively correlated with the FC between the right VRP and the left caudate. This study provides new insights into understanding the specificity of TRD striatal circuits.

EphA4/ephrinA3 reverse signaling mediated downregulation of glutamate transporter GLAST in Müller cells in an experimental glaucoma model.

Deficiency of glutamate transporter GLAST in Müller cells may be culpable for excessive extracellular glutamate, which involves in retinal ganglion cell (RGC) damage in glaucoma. We elucidated how GLAST was regulated in rat chronic ocular hypertension (COH) model. Western blot and whole-cell patch-clamp recordings showed that GLAST proteins and GLAST-mediated current densities in Müller cells were downregulated at the early stages of COH. In normal rats, intravitreal injection of the ephrinA3 activator EphA4-Fc mimicked the changes of GLAST in COH retinas. In purified cultured Müller cells, EphA4-Fc treatment reduced GLAST expression at mRNA and protein levels, which was reversed by the tyrosine kinase inhibitor PP2 or transfection with ephrinA3-siRNA (Si-EFNA3), suggesting that EphA4/ephrinA3 reverse signaling mediated GLAST downregulation. EphA4/ephrinA3 reverse signaling-induced GLAST downregulation was mediated by inhibiting PI3K/Akt/NF-κB pathways since EphA4-Fc treatment of cultured Müller cells reduced the levels of p-Akt/Akt and NF-κB p65, which were reversed by transfecting Si-EFNA3. In Müller cells with ephrinA3 knockdown, the PI3K inhibitor LY294002 still decreased the protein levels of NF-κB p65 in the presence of EphA4-Fc, and the mRNA levels of GLAST were reduced by LY294002 and the NF-κB inhibitor SN50, respectively. Pre-injection of the PI3K/Akt pathway activator 740 Y-P reversed the GLAST downregulation in COH retinas. Western blot and TUNEL staining showed that transfecting of Si-EFNA3 reduced Müller cell gliosis and RGC apoptosis in COH retinas. Our results suggest that activated EphA4/ephrinA3 reverse signaling induces GLAST downregulation in Müller cells via inhibiting PI3K/Akt/NF-κB pathways, thus contributing to RGC damage in glaucoma.

Isolation, purification and PEG-mediated transient expression of mesophyll protoplasts in Camellia oleifera.

BACKGROUND: Camellia oleifera (C. oleifera) is a woody edible oil crop of great economic importance. Because of the lack of modern biotechnology research, C. oleifera faces huge challenges in both breeding and basic research. The protoplast and transient transformation system plays an important role in biological breeding, plant regeneration and somatic cell fusion. The objective of this present study was to develop a highly efficient protocol for isolating and purifying mesophyll protoplasts and transient transformation of C. oleifera. Several critical factors for mesophyll protoplast isolation from C. oleifera, including starting material (leaf age), pretreatment, enzymatic treatment (type of enzyme, concentration and digestion time), osmotic pressure and purification were optimized. Then the factors affecting the transient transformation rate of mesophyll protoplasts such as PEG molecular weights, PEG4000 concentration, plasmid concentration and incubation time were explored. RESULTS: The in vitro grown seedlings of C. oleifera 'Huashuo' were treated in the dark for 24 h, then the 1st to 2nd true leaves were picked and vacuumed at - 0.07 MPa for 20 min. The maximum yield (3.5 × 107/g·FW) and viability (90.9%) of protoplast were reached when the 1st to 2nd true leaves were digested in the enzymatic solution containing1.5% (w/v) Cellulase R-10, 0.5% (w/v) Macerozyme R-10 and 0.25% (w/v) Snailase and 0.4 M mannitol for 10 h. Moreover, the protoplast isolation method was also applicable to the other two cultivars, the protoplast yield for 'TXP14' and 'DP47' was 1.1 × 107/g·FW and 2.6 × 107/g·FW, the protoplast viability for 'TXP14' and 'DP47' was 90.0% and 88.2%. The purification effect was the best when using W buffer as a cleaning agent by centrifugal precipitation. The maximum transfection efficiency (70.6%) was obtained with the incubation of the protoplasts with 15 µg plasmid and 40% PEG4000 for 20 min. CONCLUSION: In summary, a simple and efficient system for isolation and transient transformation of C. oleifera mesophyll protoplast is proposed, which is of great significance in various aspects of C. oleifera research, including the study of somatic cell fusion, genome editing, protein function, signal transduction, transcriptional regulation and multi-omics analyses.

Spontaneous coronary artery dissection and atherosclerosis in a young man with systemic lupus erythematosus: A case report and literature review.

Background: Spontaneous coronary artery dissection (SCAD) is a rare coronary artery disease that frequently occurs in young, female patients without risk factors, and conservative treatment is often recommended for its management. The patient reported here is a male patient with systemic lupus erythematosus (SLE). Case summary: We described a 28-year-old man with SLE who presented with acute ST-segment elevation myocardial infarction (STEMI), and was diagnosed with SCAD through a long dissection of the left anterior descending branch (LAD) by coronary angiography. The patient was treated with percutaneous coronary intervention (PCI) with stent implantation. Ten years later, he developed in-stent stenosis and other coronary atherosclerosis and was retreated with PCIs. Based on this case and according to the literature review, the existing treatment and prognosis of SLE with spontaneous coronary artery dissection and atherosclerosis are discussed. Conclusion: Cardiovascular complications should be considered in patients with systemic lupus erythematosus, although they may not initially be atherosclerotic diseases. Attention should be paid to distinguish spontaneous coronary dissection in order to minimize missed or delayed diagnoses and take appropriate managements, as well as the development of atherosclerosis in SLE patients, and timely intervention has a better prognosis.

Application of the Delphi Method in the Study of Depressive Disorder.

Depressive disorder is a common mental disorder that has a high prevalence and low visiting rate, which caused patients years lived with disability. Due to the complexity of the depressive disorder, the Delphi method is a better choice compared with other commonly used methods, which provides a new perspective for the prevention and treatment of depression. This article will summarize the clinical studies of depressive disorders using the Delphi method from four perspectives, and summarize the advantages and disadvantages of the Delphi method in depressive disorders research, arguing that the Delphi method can cross the gap between clinical research and clinical practice, and is a highly practical part of the research process.

Soluble tumor necrosis factor-alpha-induced hyperexcitability contributes to retinal ganglion cell apoptosis by enhancing Nav1.6 in experimental glaucoma.

BACKGROUND: Neuroinflammation plays an important role in the pathogenesis of glaucoma. Tumor necrosis factor-alpha (TNF-α) is a major pro-inflammatory cytokine released from activated retinal glial cells in glaucoma. Here, we investigated how TNF-α induces retinal ganglion cell (RGC) hyperexcitability and injury. METHODS: Whole-cell patch-clamp techniques were performed to explore changes in spontaneous firing and evoked action potentials, and Na+ currents in RGCs. Both intravitreal injection of TNF-α and chronic ocular hypertension (COH) models were used. Western blotting, immunofluorescence, quantitative real-time polymerase chain reaction (q-PCR), and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) techniques were employed to investigate the molecular mechanisms of TNF-α effects on RGCs. RESULTS: Intravitreal injection of soluble TNF-α significantly increased the spontaneous firing frequencies of RGCs in retinal slices. When the synaptic transmissions were blocked, more than 90% of RGCs still showed spontaneous firing; both the percentage of cells and firing frequency were higher than the controls. Furthermore, the frequency of evoked action potentials was also higher than the controls. Co-injection of the TNF-α receptor 1 (TNFR1) inhibitor R7050 eliminated the TNF-α-induced effects, suggesting that TNF-α may directly act on RGCs to induce cell hyperexcitability through activating TNFR1. In RGCs acutely isolated from TNF-α-injected retinas, Na+ current densities were upregulated. Perfusing TNF-α in RGCs of normal rats mimicked this effect, and the activation curve of Na+ currents shifted toward hyperpolarization direction, which was mediated through p38 MAPK and STAT3 signaling pathways. Further analysis revealed that TNF-α selectively upregulated Nav1.6 subtype of Na+ currents in RGCs. Similar to observations in retinas of rats with COH, intravitreal injection of TNF-α upregulated the expression of Nav1.6 proteins in both total cell and membrane components, which was reversed by the NF-κB inhibitor BAY 11-7082. Inhibition of TNFR1 blocked TNF-α-induced RGC apoptosis. CONCLUSIONS: TNF-α/TNFR1 signaling induces RGC hyperexcitability by selectively upregulating Nav1.6 Na+ channels, thus contributing to RGC apoptosis in glaucoma.

Construction of a molybdenum and copper co-doped nickel phosphide with lattice distortion for highly efficient electrochemical water splitting.

A self-supported dual-cation (Mo,Cu) co-doped Ni2P@ nickel foam catalyst (Mo,Cu-Ni2P@NF) has been prepared, and the co-doped samples can distort the lattice and expose a larger specific surface area, which provides more reaction locations, and exhibit an efficient water splitting performance.

Rac1 conditional deletion attenuates retinal ganglion cell apoptosis by accelerating autophagic flux in a mouse model of chronic ocular hypertension.

Autophagy has a fundamental role in maintaining cell homeostasis. Although autophagy has been implicated in glaucomatous pathology, how it regulates retinal ganglion cell (RGC) injury is largely unknown. In the present work, we found that biphasic autophagy in RGCs occurred in a mouse model of chronic ocular hypertension (COH), accompanied by activation of Rac1, a member of the Rho family. Rac1 conditional knockout (Rac1 cKO) in RGCs attenuated RGC apoptosis, in addition to blocking the increase in the number of autophagosomes and the expression of autophagy-related proteins (Beclin1, LC3-II/I, and p62) in COH retinas. Electron micrograph and double immunostaining of LAMP1 and LC3B showed that Rac1 cKO accelerated autolysosome fusion in RGC axons of COH mice. Inhibiting the first autophagic peak with 3-methyladenine or Atg13 siRNA reduced RGC apoptosis, whereas inhibiting the second autophagic peak with 3-MA or blocking autophagic flux by chloroquine increased RGC apoptosis. Furthermore, Rac1 cKO reduced the number of autophagosomes and apoptotic RGCs induced by rapamycin injected intravitreally, which suggests that Rac1 negatively regulates mTOR activity. Moreover, Rac1 deletion decreased Bak expression and did not interfere with the interaction of Beclin1 and Bcl-2 or Bak in COH retinas. In conclusion, autophagy promotes RGC apoptosis in the early stages of glaucoma and results in autophagic cell death in later stages. Rac1 deletion alleviates RGC damage by regulating the cross talk between autophagy and apoptosis through mTOR/Beclin1-Bak. Interfering with the Rac1/mTOR signaling pathway may provide a new strategy for treating glaucoma.

Activated ephrinA3/EphA4 forward signaling induces retinal ganglion cell apoptosis in experimental glaucoma.

Previous studies have demonstrated that EphA4 participates in neuronal injury, and there is a strong interaction between ephrinA3 and EphA4. In this study, we showed that in a rat chronic ocular hypertension (COH) experimental glaucoma model, expression of EphA4 and ephrinA3 proteins was increased in retinal cells, including retinal ganglion cells (RGCs) and Müller cells, which may result in ephrinA3/EphA4 forward signaling activation on RGCs, as evidenced by increased p-EphA4/EphA4 ratio. Intravitreal injection of ephrinA3-Fc, an activator of EphA4, mimicked the effect of COH on p-EphA4/EphA4 and induced an increase in TUNEL-positive signals in normal retinas, which was accompanied by dendritic spine retraction and thinner dendrites in RGCs. Furthermore, Intravitreal injection of ephrinA3-Fc increased the levels of phosphorylated src and GluA2 (p-src and p-GluA2). Co-immunoprecipitation assay demonstrated interactions between EphA4, p-src and GluA2. Intravitreal injection of ephrinA3-Fc reduced the expression of GluA2 proteins on the surface of normal retinal cells, which was prevented by intravitreal injection of PP2, an inhibitor of src-family tyrosine kinases. Pre-injection of PP2 or the Ca2+-permeable GluA2-lacking AMPA receptor inhibitor Naspm significantly and partially reduced the number of TUNEL-positive RGCs in the ephrinA3-Fc-injected and COH retinas. Our results suggest that activated ephrinA3/EphA4 forward signaling promoted GluA2 endocytosis, then resulted in dendritic spine retraction of RGCs, thus contributing to RGC apoptosis in COH rats. Attenuation of the strength of ephrinA/EphA signaling in an appropriate manner may be an effective way for preventing the loss of RGCs in glaucoma.

Clinical and morpho-molecular classifiers for prediction of hepatocellular carcinoma prognosis and recurrence after surgical resection.

BACKGROUND: Approximately 50% hepatocellular carcinoma (HCC) patients die within 5 year after surgical resection. The present staging systems do not fully allow to accurately predict the HCC prognosis and recurrence. This study aimed to identify clinicopathological characteristics and molecular markers to establish classifiers to predict the 5-year overall survival (OS) and the 3-year recurrence in HCC patients post-operatively. METHODS: We enrolled 647 HCC patients from two institutions, underwent surgical resection and divided the patients into one training and two validation cohorts. Clinicopathologic characteristics and tumor protein expression of 29 biomarkers by immunohistochemical (IHC) analysis were used to develop and validate a prognostic and a recurrent classifier, using the maximum relevance minimum redundancy algorithm jointly with the multivariable regression method. RESULTS: The prognostic classifier distinguished HCC patients into high- and low-probability survival groups with significant differences in 5-year OS rate in all three cohorts (training cohort: 57.36% vs. 22.97%; p < 0.0001; internal validation cohort: 61.90% vs. 28.85%; p < 0.0001; independent validation cohort: 64.28% vs. 22.45%; p < 0.0001). The recurrent classifier also demonstrated good discrimination in all three cohorts. CONCLUSION: This study presented a prognostic classifier and a recurrent classifier using clinicopathologic and IHC characteristics. The developed classifiers stratified HCC patients into high- and low-probability survival or recurrent groups, which can help clinicians judge whether adjuvant therapy is beneficial post-operatively.

Development and validation of a novel score for fibrosis staging in patients with chronic hepatitis B.

BACKGROUND & AIMS: Non-invasive assessment methods for liver fibrosis are urgently needed. The present study aimed to develop a novel diagnostic model for fibrosis staging in patients with chronic hepatitis B. METHODS: A cross-sectional set of 417 chronic hepatitis B patients who underwent liver biopsy was enrolled and the METAVIR score was adopted as the reference of fibrosis staging. RESULTS: Among thyroid hormones, only the level of free tetraiodothyronine (FT4) decreased gradually with the METAVIR fibrosis score (P < .001). FibroStage, a novel diagnosis model that incorporates data on FT4, platelets, cholinesterase, gamma-glutamyl transpeptidase, and age, was developed using the deriving set (n = 219). For the diagnosis of significant fibrosis, the FibroStage model had a significantly higher area under the receiver operating curve than did the FibroIndex, Forn, and Lok models (all of P < .01) and tended to better than the fibrosis-4 (P = .0791) but comparable with the aspartate transaminase-to-platelet ratio index model (P = .1694). For the diagnosis of advanced fibrosis, FibroStage had a higher area under the receiver operating curve than did the aspartate transaminase-to-platelet ratio index, FibroIndex, Forn, and Lok models (all of P < .05) and had a comparable area under the receiver operating curve with the fibrosis-4 model (P = .2109). For the diagnosis of cirrhosis, the area under the receiver operating curve of FibroStage was higher than those of the aspartate transaminase-to-platelet ratio index, fibrosis-4, FibroIndex, and Lok (all of P < .05) models and was comparable with Forn (P = .1649). These results was validated by a validation set (n = 198). CONCLUSION: FT4 may be an indicator for fibrosis staging in chronic hepatitis B patients. FibroStage is a better model than aspartate transaminase-to-platelet ratio index, fibrosis-4, FibroIndex, Forn, and Lok for the comprehensively diagnosis of significant and advanced fibrosis and cirrhosis.