Tumor polo-like kinase 4 protein expression reflects lymphovascular invasion, higher Federation of Gynecology and Obstetrics stage, and shortened survival in endometrial cancer patients who undergo surgical resection.

BACKGROUND: Polo-like kinase 4 (PLK4) serves as a marker for tumor features and poor outcomes in cancers. This study aimed to explore the associations of tumor PLK4 protein expression with tumor characteristics and survival in endometrial cancer (EC) patients who underwent surgical resection. METHODS: This study included 142 EC patients who underwent surgical resection. Tumor tissue samples were obtained for tumor PLK4 protein expression detection via immunohistochemistry (IHC). RESULTS: Among EC patients, 26.1% had a PLK4 IHC score of 0, 24.6% had a score of 1-3, 27.5% had a score of 4-6, and 21.8% had a score of 7-12. Tumor PLK4 protein expression positively associated with lymphovascular invasion (P = 0.008) and Federation of Gynecology and Obstetrics (FIGO) stage (P = 0.005). Disease-free survival (DFS) was not different between patients with tumor PLK4 IHC scores > 0 and ≤ 0 (P = 0.154) but was reduced in patients with scores > 3 vs. ≤ 3 (P = 0.009) and > 6 vs. ≤ 6 (P < 0.001). Similarly, overall survival (OS) was not different between patients with scores > 0 and ≤ 0 (P = 0.322) but was shorter in patients with scores > 3 vs. ≤ 3 (P = 0.011) and > 6 vs. ≤ 6 (P = 0.006). After adjustment, a tumor PLK4 IHC score > 6 (vs. ≤ 6) (hazard ratio (HR): 3.156, P = 0.008) or > 3 (vs. ≤ 3) (HR: 3.918, P = 0.026) was independently associated with shortened DFS and OS. CONCLUSION: A tumor PLK4 IHC score > 6 or > 3 associates with shortened DFS and OS in EC patients who undergo surgical resection.

Age-related differences in the interplay of fluency and complexity in Chinese-speaking seniors' oral narratives.

BACKGROUND: Previous studies on language production in normal ageing have primarily focused on distinct dimensions of older adults' spoken language performance, such as fluency and complexity. However, little attention has been paid to the complex, interconnected relations between these dimensions. Additionally, older adults have been treated as a homogeneous group, with little consideration for the differential characteristics of language performance across different stages of ageing. AIMS: This study aims to investigate how increasing age impacts Chinese seniors' oral language performance, focusing on fluency (articulation rate and dysfluency rate), complexity (lexical and syntactic) and the potential interactions between these dimensions. METHODS & PROCEDURES: Spontaneous oral narratives were collected from 60 normally ageing individuals, who were categorised into three groups: young-old (60-69 years old), middle-old (70-79 years old) and old-old (≥80 years old). Four measures for assessing language performance, namely, articulation rate, dysfluency rate, lexical complexity and syntactic complexity, were derived from the oral narratives. Dynamic systems techniques, including moving correlations, locally estimated scatterplot smoothing and Monte Carlo simulations, were employed for data analysis. OUTCOMES & RESULTS: This study revealed two major findings. First, across different age groups, the seniors' oral narratives significantly differed in the aspect of articulation rate and syntactic complexity. Specifically, both the young-old and the middle-old groups exhibited significantly higher articulation rates than the old-old group; the middle-old group also demonstrated significantly higher syntactic complexity compared to the old-old group. Second, the distinct subsystems (i.e., articulation rate, dysfluency rate, lexical and syntactic complexity) of seniors' oral narratives demonstrated varying interactions across different stages of ageing. While these subsystems tended to coordinate with each other in young-old individuals, they exhibited a greater tendency to compete in middle-old and old-old individuals. CONCLUSIONS & IMPLICATIONS: The findings reveal that subsystems of older adults' oral narratives display varying interactions with the increase of age, indicating that focusing solely on one dimension of language performance may result in inaccurate or misleading conclusions. Therefore, a multi-index comprehensive assessment should be employed for the enhancement of clinical evaluations of language performance in older adults. Additionally, it is vital to consider the interactional patterns (i.e., support or competition) between language subsystems when assessing language performance in normal ageing. WHAT THIS PAPER ADDS: What is already known on the subject Previous research on language production in normal ageing has primarily focused on distinct dimensions of older adults' spoken language performance, such as fluency, vocabulary richness and grammatical complexity, overlooking the intricate interconnections between these dimensions. However, investigating these connections is significant for a thorough and in-depth understanding of language production in late adulthood, which operates as a system comprising interconnected components. Furthermore, existing studies have predominantly treated older adults as a homogeneous group, comparing their language use to that of young people. This approach lacks justification, given the substantial variations in language use among seniors at different stages of ageing. What this paper adds to existing knowledge The present findings illuminate the dynamic nature of language production in normal ageing. Not only do the distinct dimensions or subsystems of older adults' oral narratives (e.g., articulation rate, dysfluency rate, syntactic complexity) change with age, but more important, the ways in which these subsystems interact with each other also evolve with age, resulting in changing states of spoken language production in the ageing process. More specifically, our study provides evidence that the interactions among subsystems of older adults' oral narratives predominately transition from supportive relationships in earlier stages to competitive ones at later stages of ageing. What are the potential or actual clinical implications of this work? The present study suggests the use of multiple linguistic indices related to various aspects of language performance to assess the spoken language production of older adults. This is highlighted by the observation that various dimensions of older adults' oral narratives continuously interact with one another across different stages of ageing, and hence focusing solely on one dimension of language performance tends to lead to inaccurate or misleading results. Additionally, the patterns of interaction (i.e., support or competition) between different dimensions of language performance may reflect older adults' capacity to coordinate and control attentional resources and therefore should be taken into consideration in clinical evaluations of language performance in older adults.

Bifunctional photoelectrochemical aptasensor based on heterostructured Ag3PO4/Ag/TiO2 nanorod array for determination of two tumor markers.

Constructing of heterostructures can significantly improve the photoelectrical (PEC) response signal by promoting the migration and suppressing the recombination of photogenerated carries. A bifunctional PEC sensing platform was designed for simultaneous high-performance detection of mucin-1 (MUC1) and carcinoembryonic antigen (CEA), which was based on generated Z-scheme heterostructured Ag3PO4/Ag/TiO2 nanorod arrays (NAs) and enzyme-mediated catalytic precipitation by alkaline phosphatase (ALP) and Au/hollow Co3O4 polyhedron. The proposed aptasensor displayed linear ranges of 1.0-100 ng mL-1 and 0.1-50 ng mL-1 for MUC1 and CEA with limit of detections of 0.430 and 0.058 ng mL-1, respectively. This strategy offers potential applications for early diagnosis, monitoring progression, and even evaluating the prognosis of breast cancer in practice.

E-cadherin to N-cadherin switching in the TGF-ß1 mediated retinal pigment epithelial to mesenchymal transition.

A serious form of ocular fibrotic disease is proliferative vitreoretinopathy (PVR) that can ultimately lead to blindness. While the pathogenesis of PVR is known to be closely tied to retinal pigment epithelial (RPE) cell epithelial-mesenchymal transition (EMT) characterized by E-cadherin downregulation and N-cadherin upregulation. Herein, we developed a model of transforming growth factor-ß1 (TGF-ß1)-induced EMT using human RPE (hRPE) cells as a tool for exploring the mechanistic basis for E-cadherin to N-cadherin switching. This analysis revealed that the loss of E-cadherin led to the separation of ß-catenin from the catenin-cadherin complex whereupon it underwent nuclear entry to activate zinc finger E-box binding homeobox 1 (ZEB1), in turn promoting N-cadherin upregulation in this biological context. E-cadherin overexpression was sufficient to inhibit this EMT process and proliferation in RPE cells, further constraining their TGF-ß1-induced apoptosis.

Comparing Photoactivities of Dissolved Organic Matter Released from Rice Straw-Pyrolyzed Biochar and Composted Rice Straw.

Here, we systematically compared the photoactivity and photobleaching behavior between dissolved black carbon (DBC) from rice straw biochar and leached dissolved organic carbon (LDOC) from rice straw compost using complementary techniques. The Fourier transform-ion cyclotron resonance mass spectrometry (FT-ICR MS) analysis showed that DBC was dominated by polycyclic aromatic (55.1%) and tannin-like molecules (24.1%), while LDOC was dominated by lignin-like (58.9%) and tannin-like molecules (19.7%). Under simulated sunlight conditions, DBC had much higher apparent quantum yields for 3DOM* and 1O2 but much lower apparent quantum yields for •OH than LDOC. After a 168 h irradiation, the total number of LDOC formulas identified by FT-ICR MS decreased by 40.1% with concurrent increases in O/C and H/C ratios and also decreases in double bond equivalence minus oxygen (DBE - O) and average molecular weight identified by gel permeation chromatography. However, despite the large decreases in UVA254 and DOC, the total number of DBC formulas decreased only by 12.0% with nearly unchanged O/C ratio, DBE - O values, molecular weight distribution, and benzenepolycarboxylic aromatic condensation (BACon) index regardless of the decreased percentage of condensed aromatic carbon (ConAC %). Compared with LDOC, the photolysis of DBC was much less oxidative and destructive mainly via breakup of a small portion of the highly condensed aromatic rings, probably accompanied by photodecarboxylation.

Long non-coding RNA ANRIL interacts with microRNA-34a and microRNA-125a, and they all correlate with disease risk and severity of Parkinson's disease.

BACKGROUND: This study aimed to investigate the correlation of long non-coding RNA antisense non-coding RNA in the INK4 locus (lncRNA ANRIL) and its target microRNAs (microRNA-34a (miR-34a) and microRNA-125a (miR-125a)) with disease risk and severity of Parkinson's disease (PD). METHODS: Seventy-eight PD patients and 78 age-/gender-matched controls were consecutively enrolled. Their peripheral blood mononuclear cell samples were collected and proposed for the reverse-transcription quantitative polymerase chain reaction to complete lncRNA ANRIL, miR-34a, and miR-125a measurements. RESULTS: LncRNA ANRIL was upregulated, while miR-34a and miR-125a were downregulated in PD patients compared to controls (all p < 0.001). Further, they all showed certain values for PD risk identification by ROC curve analyses, among which lncRNA ANRIL showed the highest AUC (AUC: 0.879, 95% CI: 0.824-0.934). Furthermore, lncRNA ANRIL negatively correlated with miR-34a (p = 0.016) and miR-125a (p = 0.005) in PD patients, but not in controls. In addition, lncRNA ANRIL was observed to positively associate with UPDRS-I score (p = 0.029), UPDRS-III score (p = 0.006), and UPDRS-IV score (p = 0.033), while negatively correlated with MMSE score (p = 0.003). These associations were less distinct as to miR-34a and miR-125a. CONCLUSION: LncRNA ANRIL interacts with miR-34a and miR-125a in PD patients, and they all correlate with disease risk and severity of PD.

Disturbance of functional and effective connectivity of the salience network involved in attention deficits in right temporal lobe epilepsy.

The salience network (SN) acts as a switch that generates transient control signals to regulate the executive control network (ECN) and the default mode network (DMN) and has been implicated in cognitive processes. Temporal lobe epilepsy (TLE) is usually accompanied by different types of cognitive deficits, but whether it is associated with dysfunctional connectivity of the SN remains unknown. To address this, thirty-six patients with right TLE (rTLE) and thirty-six healthy controls (HCs) were recruited for the present study. All of the participants were subjected to attention network test (ANT) and resting-state functional resonance imaging (rs-fMRI) scanning. The patient group showed deficits in attention performance. Moreover, the functional connectivity (FC) and effective connectivity (EC) were analyzed based on key SN hubs (the anterior cingulate cortex (ACC) and the bilateral anterior insula (AI)). When compared with those in the HC group, the ACC showed increased FC with the left middle frontal gyrus and the left precentral gyrus, and the right AI showed decreased FC with the right precuneus and the right superior occipital gyrus in the patient group. The EC analysis revealed an increased inflow of information from the left middle temporal gyrus to the ACC and the right AI and an increased outflow of information from the bilateral AI to the left middle frontal gyrus. Furthermore, in the correlation analysis, the abnormal EC from the right AI to the left middle temporal gyrus was positively correlated with the executive control effect. These findings demonstrated aberrant modulation of the SN in rTLE, which was particularly characterized by dysfunctional connectivity between the SN and key brain regions in the DMN and ECN. Elucidation of this effect may further contribute to the comprehensive understanding of the neural mechanisms of the SN in regard to attention deficits in patients with TLE.

Analysis of cuticular wax constituents and genes that contribute to the formation of 'glossy Newhall', a spontaneous bud mutant from the wild-type 'Newhall' navel orange.

Navel orange (Citrus sinensis [L.] Osbeck) fruit surfaces contain substantial quantities of cuticular waxes, which have important eco-physiological roles, such as water retention and pathogen defense. The wax constituents of ripe navel orange have been studied in various reports, while the wax changes occurring during fruit development and the molecular mechanism underlying their biosynthesis/export have not been investigated. Recently, we reported a spontaneous bud mutant from the wild-type (WT) 'Newhall' Navel orange. This mutant displayed unusual glossy fruit peels and was named 'glossy Newhall' (MT). In this study, we compared the developmental profiles of the epicuticular and intracuticular waxes on the WT and MT fruit surfaces. The formation of epicuticular wax crystals on the navel orange surface was shown to be dependent on the accumulation of high amounts of aliphatic wax components with trace amounts of terpenoids. In sharp contrast, the underlying intracuticular wax layers have relatively low concentrations of aliphatic wax components but high concentrations of cyclic wax compounds, especially terpenoids at the late fruit developmental stages. Our work also showed that many genes that are involved in wax biosynthesis and export pathways were down-regulated in MT fruit peels, leading to a decrease in aliphatic wax component amounts and the loss of epicuticular wax crystals, ultimately causing the glossy phenotype of MT fruits.

Novel Smad proteins localize to IR-induced double-strand breaks: interplay between TGFß and ATM pathways.

Cellular damage from ionizing radiation (IR) is in part due to DNA damage and reactive oxygen species, which activate DNA damage response (DDR) and cytokine signaling pathways, including the ataxia telangiectasia mutated (ATM) and transforming growth factor (TGF)ß/Smad pathways. Using classic double-strand breaks (DSBs) markers, we studied the roles of Smad proteins in DDR and the crosstalk between TGFß and ATM pathways. We observed co-localization of phospho-Smad2 (pSmad2) and Smad7 with DSB repair proteins following low and high linear energy transfer (LET) radiation in human fibroblasts and epithelial cells. The decays of both foci were similar to that of γH2AX foci. Irradiation with high LET particles induced pSmad2 and Smad7 foci tracks indicating the particle trajectory through cells. pSmad2 foci were absent in S phase cells, while Smad7 foci were present in all phases of cell cycle. pSmad2 (but not Smad7) foci were completely abolished when ATM was depleted or inactivated. In contrast, a TGFß receptor 1 (TGFßR1) inhibitor abrogated Smad7, but not pSmad2 foci at DSBs sites. In summary, we suggest that Smad2 and Smad7 contribute to IR-induced DSB signaling in an ATM or TGFßR1-dependent manner, respectively.

Functional redundancy between DNA ligases I and III in DNA replication in vertebrate cells.

In eukaryotes, the three families of ATP-dependent DNA ligases are associated with specific functions in DNA metabolism. DNA ligase I (LigI) catalyzes Okazaki-fragment ligation at the replication fork and nucleotide excision repair (NER). DNA ligase IV (LigIV) mediates repair of DNA double strand breaks (DSB) via the canonical non-homologous end-joining (NHEJ) pathway. The evolutionary younger DNA ligase III (LigIII) is restricted to higher eukaryotes and has been associated with base excision (BER) and single strand break repair (SSBR). Here, using conditional knockout strategies for LIG3 and concomitant inactivation of the LIG1 and LIG4 genes, we show that in DT40 cells LigIII efficiently supports semi-conservative DNA replication. Our observations demonstrate a high functional versatility for the evolutionary new LigIII in DNA replication and mitochondrial metabolism, and suggest the presence of an alternative pathway for Okazaki fragment ligation.

Unraveling the photochemical behavior of dissolved organic matter derived from hydrothermal carbonization process water: Insights from molecular transformation and photoactive species.

Hydrothermal carbonization process water (HTPW) has been utilized as a substitute for chemical fertilizers in agricultural applications. However, the input of HTPW into paddy water, particularly the significant proportion of dissolved organic matter (DOM) in HTPW (DOM-HTPW), directly engages in photochemical transformations, a phenomenon often overlooked. This study observed a consistent decrease in humification (SUVA280, 7.7-53.9%) and aromaticity (SUVA254, 6.1-40.0%) of DOM-HTPW after irradiation. The primary active photobleaching components of DOM-HTPW varied depending on the feedstock, such as protein for chicken manure DOM-HTPW and lignin for rice straw DOM-HTPW. The photochemical activity of DOM-HTPW was augmented by its lower molecular weight and higher hydrophilic composition, particularly evident in chicken manure DOM-HTPW, which exhibited higher generation rates for 1O2 (35.1-37.1%), 3DOM* (32.8-43.9%), and O2•- (28.6-48.8%) as measured by molecular probes. DOM-HTPW effectively facilitated the phototransformation of tetracycline, with the contribution of O2•- being more significant than 3DOM* and 1O2. These findings shed new light on the understanding the photochemical processes of DOM-HTPW as exogenous DOM and the interconnected fate of contaminants in aquatic environments.

Evaluation of the Effect of Scleral Buckling on Anterior Segment and Refractive Changes Using Anterior Segment Optical Coherence Tomography.

PURPOSE: To evaluate the changes of anterior segment and refractive parameters after scleral buckling (SB) surgery for uncomplicated rhegmatogenous retinal detachment (RRD) using anterior segment optical coherence tomography (AS-OCT). METHODS: Thirty-six RRD eyes were consecutively enrolled. Analysis concerned the central corneal thickness (CCT), anterior chamber depth (ACD), anterior chamber volume (ACV), iris-trabecular contact (ITC), angel opening distance (AOD), angle recess area (ARA), trabecular-iris space area (TISA)，trabecular iris angle (TIA) and refractive parameters, including average keratometry (AvgK), cylindrical power (CYL), regular astigmatism, asymmetry and high order irregularity (HOI) at baseline and 1 day, 1 month, 2 months, 6 months and 12 months postoperatively. AS-OCT was performed at RRD diagnosis and day 1, week 1, month 1 and month 6 after SB to evaluate the scleral buckling. RESULTS: A statistically significant postoperative CCT increase, ACD and ACV decrease were observed at 1 day and 1 month postoperatively. ITC analysis showed that the angle of the entire circumference narrowed at 1 month postoperatively. There was a significant decrease in all the angle parameters (AOD500/750, ARA500/750, TISA500/750, and ARA500/750) at 1 day and 1 month after SB surgery. However, all of the above parameters returned to the preoperative level at 12 months. Refractive parameters including AvgK, regular astigmatism, CYL, asymmetry, and HOI of anterior corneal surface and total corneal increased on the 1 day and 1 month after SB surgery and persisted even after 12 months follow-up. However, there was no significant difference in refractive parameters of posterior corneal surface during follow-up. CONCLUSION: The changes in the structure of anterior segments after SB surgery were almost returned to the preoperative levels at 12 months postoperatively. However, SB surgery has a long-term effect on refractive parameters throughout a 12-month follow-up.

Sulfur-regulated CoSe2 nanowires with high-charge active centers for electrochemical nitrate reduction to ammonium.

Developing high-efficiency electrocatalysts for nitrate-to-ammonia transformation holds significant promise for the production of ammonia, a crucial component in agricultural fertilizers and as a carbon-free energy carrier. In this study, we propose a viable strategy involving sulfur doping to modulate both the microstructure and electronic properties of CoSe2 for nitrate reduction. This approach remarkably enhances the conversion of nitrate to ammonia by effectively regulating the adsorption capability of nitrogenous intermediates. Specifically, sulfur-doped CoSe2 nanowires (S-CoSe2 NWs) exhibit a peak faradaic efficiency of 93.1% at -0.6 V vs. RHE and achieve the highest NH3 yield rate of 11.6 mg h-1 cm-2. Mechanistic investigations reveal that sulfur doping facilitates the creation of highly charged active sites, which enhance the adsorption of nitrite and subsequent hydrogenation, leading to improved selectivity towards ammonia production.

Smad7 foci are present in micronuclei induced by heavy particle radiation.

DNA damage and reactive oxygen species (ROS) generated by ionizing radiation (IR) activate DNA damage response (DDR) and cytokine signaling pathways, including double strand break (DSB) repair and TGFß/Smad signaling pathway. Proteins assembled at IR-induced DSB sites can be visualized as foci, including γH2AX, 53BP1, ATM and ATF2. Unrepaired DSBs are thought to be one origin of micronuclei (MN), an indicator of genotoxic stress and chromosomal instability. Studies have detected γH2AX in IR-induced MN, indicating the presence of DSB in MN. Previously we reported that TGFß downstream proteins Smad7 and phospho-Smad2 (pSmad2) co-localized with DDR proteins following radiation. Here we studied the status of Smad7 and pSmad2 in MN post high linear energy transfer (LET) radiation in human normal and cancerous cells. We observed γH2AX foci in IR-induced MN, whereas 53BP1 and ATF2 were absent. Interestingly, Smad7 foci, but not pSmad2, were detectable in both spontaneous and IR-induced MN. We compared the effect of particle track structures on the yield of MN using 5.6MeV/u boron (B) and 600MeV/u iron (Fe) particles with similar LET (200 and 180keV/µm, respectively) in human fibroblasts. The frequency of MN induced by B was lower than that by Fe particles, albeit the proportion of Smad7-positive to Smad7-negative MN remained constant. An increased frequency of spontaneous MN, with slightly higher ratio of Smad7 or γH2AX positive, was found in human prostate cancer cells (PC3) compared to normal cells. 24h after 1Gy of Fe particles exposure, the yield of MN increased, and the majority (∼70%) carried γH2AX and Smad7. Phospho-ATM (Ser1981) foci were found in both spontaneous and IR-induced MN in PC3 cells, displaying a much lower frequency compared to γH2AX and Smad7. Our data suggest a unique role of Smad7 in IR-induced MN formation, which may associate with DNA repair, apoptosis and genomic instability.

Post-irradiation chemical processing of DNA damage generates double-strand breaks in cells already engaged in repair.

In cells exposed to ionizing radiation (IR), double-strand breaks (DSBs) form within clustered-damage sites from lesions disrupting the DNA sugar-phosphate backbone. It is commonly assumed that these DSBs form promptly and are immediately detected and processed by the cellular DNA damage response (DDR) apparatus. This assumption is questioned by the observation that after irradiation of naked DNA, a fraction of DSBs forms minutes to hours after exposure as a result of temperature dependent, chemical processing of labile sugar lesions. Excess DSBs also form when IR-exposed cells are processed at 50°C, but have been hitherto considered method-related artifact. Thus, it remains unknown whether DSBs actually develop in cells after IR exposure from chemically labile damage. Here, we show that irradiation of 'naked' or chromatin-organized mammalian DNA produces lesions, which evolve to DSBs and add to those promptly induced, after 8-24 h in vitro incubation at 37°C or 50°C. The conversion is more efficient in chromatin-associated DNA, completed within 1 h in cells and delayed in a reducing environment. We conclude that IR generates sugar lesions within clustered-damage sites contributing to DSB formation only after chemical processing, which occurs efficiently at 37°C. This subset of delayed DSBs may challenge DDR, may affect the perceived repair kinetics and requires further characterization.

Alterations of the intestinal microbiota in age-related macular degeneration.

Purpose: Age-related macular degeneration (AMD) is the leading cause of vision loss in those over the age of 50. Recently, intestinal microbiota has been reported to be involved in the pathogenesis of ocular diseases. The purpose of this study was to discover more about the involvement of the intestinal microbiota in AMD patients. Methods: Fecal samples from 30 patients with AMD (AMD group) and 17 age- and sex-matched healthy controls (control group) without any fundus disease were collected. DNA extraction, PCR amplification, and 16S rRNA gene sequencing of the samples were performed to identify intestinal microbial alterations. Further, we used BugBase for phenotypic prediction and PICRUSt2 for KEGG Orthology (KO) as well as metabolic feature prediction. Results: The intestinal microbiota was found to be significantly altered in the AMD group. The AMD group had a significantly lower level of Firmicutes and relatively higher levels of Proteobacteria and Bacteroidota compared to those in the control group. At the genus level, the AMD patient group showed a considerably higher proportion of Escherichia-Shigella and lower proportions of Blautia and Anaerostipes compared with those in the control group. Phenotypic prediction revealed obvious differences in the four phenotypes between the two groups. PICRUSt2 analysis revealed KOs and pathways associated with altered intestinal microbiota. The abundance of the top eight KOs in the AMD group was higher than that in the control group. These KOs were mainly involved in lipopolysaccharide biosynthesis. Conclusion: The findings of this study indicated that AMD patients had different gut microbiota compared with healthy controls, and that AMD pathophysiology might be linked to changes in gut-related metabolic pathways. Therefore, intestinal microbiota might serve as non-invasive indicators for AMD clinical diagnosis and possibly also as AMD treatment targets.

Association of Interleukin-6 Polymorphisms with Schizophrenia and Depression: A Case-Control Study.

OBJECTIVE: Growing evidence suggests a crossover in genetic susceptibility to schizophrenia and depression. We aimed to investigate the association of the rs1800795 and rs1800796 polymorphisms of the IL-6 gene with schizophrenia and depression in the Han Chinese population, combined with IL-6 serum levels. METHODS: Gene sequencing and enzyme-linked immunosorbent assay were performed on 113 subjects with schizophrenia, 114 subjects with depression, and 110 healthy controls. RESULTS: Our findings showed that IL-6 concentrations in schizophrenia and depression groups were significantly higher than in the control group. The rs1800796 CC genotype and C allele were significantly associated with depression (P = .012 and P < .05, respectively). The rs1800796 CC and CG genotype was significantly associated with chronic schizophrenia (P = .020 and P = .009, respectively). Regarding the rs1800795 polymorphism, only one case of CG genotype was detected. The remainder were of the GG genotype. CONCLUSION: The IL-6 rs1800796 might serve as a protective factor for depression and schizophrenia in the Han Chinese population.

Roles of Transepithelial Electrical Resistance in Mechanisms of Retinal Pigment Epithelial Barrier and Retinal Disorders.

Transepithelial/transendothelial electrical resistance (TEER) is a widely accepted quantitative technique to measure the integrity of tight junction dynamics in cell culture models of endothelial and epithelial monolayers. The value of TEER reflects the physical structure and characteristics of epithelial/endothelial cells. TEER value is a preferred physiological indicator reflecting transport rate of ions and macromolecules through the paracellular pathway, which is used to evaluate permeability of paracellular pathway. TEER value has a high specificity for the permeability of reactive tightly connected complex. TEER value is an effective indicator to evaluate the integrity of cell barrier. The cell barrier not only controls the diffusion penetration of various substances in adjacent intercellular spaces, but also regulates the transport of ions and macromolecules across. On one hand, the cell barrier protects the body from harmful substances; on the other hand, it restricts the entry of therapeutic drugs. Therefore, with the increase of permeability in paraepithelial pathway, the TEER value decreased, otherwise, it increased. In this review article, we compared the advantages and disadvantages of the existing methods for measuring TEER and summarized the factors affecting TEER accuracy, as well as the roles of TEER in mechanisms of retinal pigment epithelial barrier and retinal disorders such as proliferative vitreoretinopathy (PVR), age-related macular degeneration (AMD), diabetic retinopathy, and retinitis pigmentosa.

Changes in transepithelial electrical resistance and intracellular ion concentration in TGF-ß-induced epithelial-mesenchymal transition of retinal pigment epithelial cells.

OBJECTIVE: This study aimed to investigate the changes in transepithelial electrical resistance (TEER) and ion concentrations, and their relationship in TGF-ß-induced epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells. METHODS: RPE cell line ARPE-19 was employed and treated with 10 ng/ml TGF-ß1 and TGF-ß2 to establish the EMT model in vitro. The EMT markers fibronectin, N-cadherin, occludin, zona occludens 1(ZO-1) and claudin-19 were investigated by western blot and immunofluorescence. CellZscope system was used to monitor the TEER values. Fluorescent probe, flow cytometry and automatic microplate reader were employed to detect the changes of Ca2+, Mg2+, Zn2+, Na+ and K+ in ARPE-19 cells. RESULTS: The TGF-ß1-induced EMT of ARPE-19 cells was marked by the disruption of the distribution of occludin, ZO-1, and claudin-19. The development of TEER was significantly disturbed in both TGF-ß1 and TGF-ß2 treatment groups. Also, the time course of the maximum slope indicated that the fastest decrease in TEER values occurred after 36 hours. The concentrations of Ca2+, Mg2+, Zn2+, and K+ increased in TGF-ß1- and TGF-ß2-treated ARPE-19 cells, while the concentration of Na+ decreased. Significant inverse correlations were detected between the concentrations of Ca2+, Mg2+, Zn2+, and K+ and TEER values in ARPE-19 cells treated with TGF-ß1. The Na+ concentration and TEER values showed a positive correlation. Similar results were observed in the TGF-ß2 treatment group. The time-effect analysis showed that the concentrations of Ca2+, Mg2+, Zn2+ and K+ increased and peaked after 72, 72, 48, and 72 h, respectively, with the extension of TGF-ß1 treatment time. In the TGF-ß2 treatment group, the Ca2+, Mg2+, Zn2+, and K+ concentrations were also upregulated and reached their highest after 72, 72, 72, and 36 h, respectively. In contrast, the concentration of Na+ decreased and reached the lowest after 48 h in the TGF-ß1 treatment group and after 72 h in the TGF-ß2 treatment group. CONCLUSION: TGF-ß1 and TGF-ß2 disrupted the ARPE-19 cell monolayer, disturbed TJs integrity, downregulated TEER values, and changed intracellular ion permeability. These findings might help further understand the EMT of RPE cells during PVR.

Cytokine profiling in patients with polypoidal choroidal vasculopathy before and after intravitreal injection of ranibizumab.

OBJECTIVE: This study aims to investigate the cytokines profiling in the aqueous humor of patients with polypoidal choroidal vasculopathy (PCV) before and after intravitreal ranibizumab injection (IVR). METHODS: 14 patients clinically diagnosed with PCV and 15 cataract patients of similar age and gender (control group) were included. Throughout the cataract surgery and IVR, aqueous humor samples were collected from the PCV and control groups. RESULTS: The levels of macrophage inflammatory protein 1ß (MIP-1ß) and normal T cell expressed and secreted (RANTES) in PCV patients were significantly lower than control subjects (P=0.045 and P=0.004, respectively). The concentration of vascular endothelial growth factor-A (VEGF-A) was significantly higher than the control group (P=0.003). The level of MIP-1ß was greatly increased in PCV patients compared to prior to IVR (P=0.001). After IVR, the level of VEGF-A in PCV patients were considerably lower compared to before IVR (P=0.001). There was no link between the expression of several cytokines (MCP-1, MIP-1, Eotaxin, G-CSF, IL-8, IL-6, IL-5, IP-10 and IFN-γ) in the aqueous humor of PCV patients before and after intravitreal ranibizumab injection (IVR). The association between IL-5 expression and central macular thickness (CMT) was discovered before IVR (P=0.02), however, the correlation between several cytokines (MCP-1, MIP-1, Eotaxin, G-CSF, IL-8, IL-6, IL-5, IP-10 and IFN-γ) was discovered in PCV patients after IVR. CONCLUSION: Based on our findings, we discovered that the production of neovascularization in PCV patients is driven by both angiogenic and inflammatory factors, with a correlation seen between several cytokines.