EXOSC10 is a novel hepatocellular carcinoma prognostic biomarker: a comprehensive bioinformatics analysis and experiment verification.

Background: Hepatocellular carcinoma (HCC) is a common malignant tumor. There are few studies on EXOSC10 (exosome component 10) in HCC; however, the importance of EXOSC10 for HCC remains unclear. Methods: In the study, the prognosis value of EXOSC10 and the immune correlation were explored by bioinformatics. The expression of EXOSC10 was verified by tissue samples from clinical patients and in vitro experiment (liver cancer cell lines HepG2, MHCC97H and Huh-7; normal human liver cell line LO2). Immunohistochemistry (IHC) was used to detect EXOSC10 protein expression in clinical tissue from HCC. Huh-7 cells with siEXOSC10 were constructed using lipofectamine 3000. Cell counting kit 8 (CCK-8) and colony formation were used to test cell proliferation. The wound healing and transwell were used to analyze the cell migration capacity. Mitochondrial membrane potential, Hoechst 33342 dye, and flow cytometer were used to detect the change in cell apoptosis, respectively. Differential expression genes (DEGs) analysis and gene set enrichment analysis (GSEA) were used to investigate the potential mechanism of EXOSC10 and were verified by western blotting. Results: EXOSC10 was highly expressed in tissues from patients with HCC and was an independent prognostic factor for overall survival (OS) in HCC. Increased expression of EXOSC10 was significantly related to histological grade, T stage, and pathological stage. Multivariate analysis indicated that the high expression level of EXOSC10 was correlated with poor overall survival (OS) in HCC. GO and GSEA analysis showed enrichment of the cell cycle and p53-related signaling pathway. Immune analysis showed that EXOSC10 expression was a significant positive correlation with immune infiltration in HCC. In vitro experiments, cell proliferation and migration were inhibited by the elimination of EXOSC10. Furthermore, the elimination of EXOSC10 induced cell apoptosis, suppressed PARP, N-cadherin and Bcl-2 protein expression levels, while increasing Bax, p21, p53, p-p53, and E-cadherin protein expression levels. Conclusions: EXOSC10 had a predictive value for the prognosis of HCC and may regulate the progression of HCC through the p53-related signaling pathway.

DNAJ heat shock protein family member C1 can regulate proliferation and migration in hepatocellular carcinoma.

Background: DNAJ heat shock protein family (Hsp40) member C1(DNAJC1) is a member of the DNAJ family. Some members of the DNAJ gene family had oncogenic properties in many cancers. However, the role of DNAJC1 in hepatocellular carcinoma (HCC) was unclear. Methods: In this study, expression and prognostic value of DNAJC1 in HCC were analyzed by bioinformatics. Quantitative real-time PCR and Western blotting were used to verify DNAJC1 expression in liver cancer cell lines. Furthermore, immunohistochemical (IHC) was used to detect DNAJC1 expression in liver cancer tissues. Subsequently, the effect of DNAJC1 on the proliferation, migration, invasion and apoptosis of HCC cells was detected by knocking down DNAJC1. Finally, gene set enrichment analysis (GSEA) was used to investigate the potential mechanism of DNAJC1 and was verified by Western blotting. Results: DNAJC1 was highly expressed in HCC and was significantly associated with the prognosis of patients with HCC. Importantly, the proliferation, migration and invasion of Huh7 and MHCC97H cells were inhibited by the knockdown of DNAJC1 and the knockdown of DNAJC1 promoted Huh7 and MHCC97H cell apoptosis. Furthermore, compared to the negative control group, DNAJC1 knockdown in Huh7 and MHCC97H cells promoted the expression of p21, p53, p-p53(Ser20), Bax and E-cadherin proteins, while inhibiting the expression of PARP, MMP9, Vimentin, Snai1, Bcl-2 and N-cadherin proteins. Conclusions: DNAJC1 had a predictive value for the prognosis of HCC. Knockdown of DNAJC1 may inhibit HCC cell proliferation, migration and invasion and promote the HCC cell apoptosis through p53 and EMT signaling pathways.

Knockout of PERK protects rat Müller glial cells against OGD-induced endoplasmic reticulum stress-related apoptosis.

BACKGROUND: The pathological basis for many retinal diseases, retinal ischemia is also one of the most common causes of visual impairment. Numerous ocular diseases have been linked to Endoplasmic reticulum(ER)stress. However, there is still no clear understanding of the relationship between ER stress and Müller glial cells during retinal ischemia and hypoxia. This study examined the effects of ER stress on autophagy and apoptosis-related proteins, as well as the microtubule-related protein tau in rMC-1 cells. METHODS: rMC-1 cells were cultured in vitro. RT-PCR、immunofluorescence and Western blotting revealed the expression levels of associated mRNAs and proteins, and the CCK-8 and flow cytometry assays detected cell apoptosis. RESULTS: The results showed that under OGD(Oxygen-glucose deprivation) conditions, the number of rMC-1 cells was decreased, the PERK/eIF2a pathway was activated, and the expressions of p-tau, LC3、Beclin1 and Caspase-12 proteins were increased. After the PERK knockout, the expression of the above proteins was decreased, and the apoptosis was also decreased. CONCLUSION: According to the findings of this study, specific downregulation of PERK expression had an anti-apoptotic effect on OGD-conditioned rMC-1 cells. There is a possibility that this is one of the mechanisms of MG cell apoptosis during retinal ischemic injury.

Improving myopia awareness via school-based myopia prevention health education among Chinese students.

AIM: To investigate the myopia awareness level, knowledge, attitude, and skills at baseline and to implement and evaluate the efficacy of myopia prevention health education among Chinese students. METHODS: A total of 1000 middle school students from 2 middle schools were invited to participate in the study, and myopia prevention health education was conducted. The students were assessed at baseline, followed by a survey. The efficacy of health education was evaluated using the self-comparison method pre- and post-health education. RESULTS: The study included 957 and 850 pre- and post-health education participants, respectively. The baseline knowledge of all respondents on myopic symptoms (87.5%), myopia is a risk of eyes (72.9%), myopia prevention (91.3%), myopia increases with age (86.7%), performing periodic eye examinations (92.8%), and one first, one foot, and one inch (84.8%) significantly increased after health education (P<0.001 for all). However, the percentage of students who still did not think it necessary to take breaks after 30-40min of continuous near work was 27.0%. The opinion that "myopia can be cured" was still present in 38.3%. CONCLUSION: Implementing school-based myopia prevention health education improves knowledge, attitudes, and skills regarding myopia among Chinese middle school students.

Influence of Lymphangio vascular (V) and perineural (N) invasion on survival of patients with resected esophageal squamous cell carcinoma (ESCC): a single-center retrospective study.

Background: Lymphangio vascular invasion (LVI) and perineural invasion (PNI) are associated with survival following resection for gastrointestinal cancer. But the relationship between LVI/PNI and survival of esophageal squamous cell carcinoma (ESCC) is still unclear. We aim to demonstrate the prognostic significance of LVI/PNI in ESCC. Methods: A total of 195 ESCC patients underwent curative surgery from 2012 to 2018 was collected in the 2nd Affiliated Hospital of Fujian Medical University. All the patients were divided into four groups based on the status of the neurovascular invasion: (1) neither LVI nor PNI (V0N0); (2) LVI alone (V1N0); (3) PNI alone (V0N1); (4) combined LVI and PNI (V1N1). First, the analysis included the Kaplan-Meier survival estimates with the Log rank test were performed to determine median overall survival (OS) in different groups divided according to the clinical factor, respectively. And the association between OS with multi clinical factors was examined using Cox regression analysis. Next, the risk factors for recurrence in patients with V1N1 were analyzed with univariate and multivariate logistic regression analyses, respectively. Results: The cases in V0N0, V1N0, V0N1, and V1N1 groups were 91 (46.7%), 62 (31.8%), 9 (4.6%) and 33 (16.9%), respectively. The OS in the four groups was different (P < 0.001). The 1-, 3- and 5-year OS in V0N0 group was higher than that in V1N1 group, respectively (1-year OS: 93.4% vs 75.8%, 3-year OS: 53.8 % vs 24.2%, 5-year OS: 48.1% vs 10.5%). The OS in stage I-II for patients with V1N1 was significantly lower than that in the other groups (V0N0, V1N0, V0N1) (P < 0.001). The postoperative adjuvant chemotherapy was a significant impact factor of OS for ESCC patients with V1N1 (P = 0.004). Lymphatic invasion and LVI were significantly prognosis factors associated (P = 0.036, P = 0.030, respectively). The ulcerative type is a risk factor for V1N1 occurance (P = 0.040). Conclusions: The LVI and PNI are important prognosis factors for ESCC patients. ESCC patients with simultaneous lymphangio vascular and perineural invasion (V1N1) showed worse OS than patients with either lymphangio vascular or perineural invasion alone (V1N0 or V0N1) or none (V0N0). In addition, adjuvant chemotherapy may prolong the OS for ESCC patients with V1N1.

An artificial intelligence model for the simulation of visual effects in patients with visual field defects.

BACKGROUND: This study aimed to simulate the visual field (VF) effects of patients with VF defects using deep learning and computer vision technology. METHODS: We collected 3,660 Humphrey visual fields (HVFs) as data samples, including 3,263 reliable 24-2 HVFs. The convolutional neural network (CNN) analyzed and converted the grayscale map of reliable samples into structured data. The artificial intelligence (AI) simulations were developed using computer vision technology. In statistical analyses, the pilot study determined 687 reliable samples to conduct clinical trials, and the two independent sample t-tests were used to calculate the difference of the cumulative gray values. Three volunteers evaluated the matching degree of shape and position between the grayscale map and the AI simulation, which was graded from 0 to100 scores. Based on the average ranking, the proportion of good and excellent grades was determined, and thus the reliability of the AI simulations was assessed. RESULTS: The reliable samples in the experimental data consisted of 1,334 normal samples and 1,929 abnormal samples. Based on the existing mature CNN model, the fully connected layer was integrated to analyze the VF damage parameters of the input images, and the prediction accuracy of the damage type of the VF defects was up to 89%. By mapping the area and damage information in the VF damage parameter quintuple data set into the real scene image and adjusting the darkening effect according to the damage parameter, the visual effects in patients were simulated in the real scene image. In the clinical validation, there was no statistically significant difference in the cumulative gray value (P>0.05). The good and excellent proportion of the average scores reached 96.0%, thus confirming the accuracy of the AI model. CONCLUSIONS: An AI model with high accuracy was established to simulate the visual effects in patients with VF defects.

Application of neural network model in assisting device fitting for low vision patients.

BACKGROUND: To explore the application of neural network models in artificial intelligence (AI)-aided devices fitting for low vision patients. METHODS: The data of 836 visually impaired people were collected in southwestern Fujian from May 2014 to May 2017. After a full eye examination, 629 low vision patients were selected from this group. Based on the visual functions, rehabilitation needs, and living quality scores of the selected patients, the professionals chose assistive devices that were the best fit for the patients. The data of these three factors were then subjected to the quantitative analysis, and the results were digitized and labeled. The final datasets were used to train a fully connected deep neural networks to obtain an AI-aided model for assistive device fitting. RESULTS: In this study, the main causes of low vision in southwestern Fujian were congenital diseases, among which congenital cataract was the most common. During the low vision AI-aided devices fitting, we found that the intermediate distance magnifier was suitable for the largest number of patients. Through quantitative analysis of the research results, it was found that AI-aided devices fitting was closely related to visual function, rehabilitation needs and quality of life. If this complex relationship can be mapped into the neural network model, AI-aided device fitting can be realized. We built a fully connected neural network model for AI-aided device fitting. The input of the model was the characteristic data of low vision patients, and the output was the forecast of suitable devices. When the threshold of the model was 0.4, the accuracy was about 80% and the F1 value was about 0.31. This threshold can be used as the classification judgment threshold of the model. CONCLUSIONS: Low vision AI-aided device fitting is closely related to visual function, rehabilitation needs, and quality of life scores. The neural network model based on full connection can achieve high accuracy in AI-aided devices fitting. It has a great impact on clinical application.

Development and Evaluation of an Ensemble-Based Data Assimilation System for Regional Reanalysis Over the Tibetan Plateau and Surrounding Regions.

The Tibetan Plateau is regarded as the Earth's Third Pole, which is the source region of several major rivers that impact more 20% the world population. This high-altitude region is reported to have been undergoing much greater rate of weather changes under global warming, but the existing reanalysis products are inadequate for depicting the state of the atmosphere, particularly with regard to the amount of precipitation and its diurnal cycle. An ensemble Kalman filter (EnKF) data assimilation system based on the limited-area Weather Research and Forecasting (WRF) model was evaluated for use in developing a regional reanalysis over the Tibetan Plateau and the surrounding regions. A 3-month prototype reanalysis over the summer months (June-August) of 2015 using WRF-EnKF at a 30-km grid spacing to assimilate nonradiance observations from the Global Telecommunications System was developed and evaluated against independent sounding and satellite observations in comparison to the ERA-Interim and fifth European Centre for Medium-Range Weather Forecasts Reanalysis (ERA5) global reanalysis. Results showed that both the posterior analysis and the subsequent 6- to 12-hr WRF forecasts of the prototype regional reanalysis compared favorably with independent sounding observations, satellite-based precipitation versus those from ERA-Interim and ERA5 during the same period. In particular, the prototype regional reanalysis had clear advantages over the global reanalyses of ERA-Interim and ERA5 in the analysis accuracy of atmospheric humidity, as well as in the subsequent downscale-simulated precipitation intensity, spatial distribution, diurnal evolution, and extreme occurrence.

Low frequency repetitive transcranial magnetic stimulation improves motor dysfunction after cerebral infarction.

Low frequency (≤ 1 Hz) repetitive transcranial magnetic stimulation (rTMS) can affect the excitability of the cerebral cortex and synaptic plasticity. Although this is a common method for clinical treatment of cerebral infarction, whether it promotes the recovery of motor function remains controversial. Twenty patients with cerebral infarction combined with hemiparalysis were equally and randomly divided into a low frequency rTMS group and a control group. The patients in the low frequency rTMS group were given 1-Hz rTMS to the contralateral primary motor cortex with a stimulus intensity of 90% motor threshold, 30 minutes/day. The patients in the control group were given sham stimulation. After 14 days of treatment, clinical function scores (National Institute of Health Stroke Scale, Barthel Index, and Fugl-Meyer Assessment) improved significantly in the low frequency rTMS group, and the effects were better than that in the control group. We conclude that low frequency (1 Hz) rTMS for 14 days can help improve motor function after cerebral infarction.

Wind estimation around the shipwreck of Oriental Star based on field damage surveys and radar observations.

Based on observational analyses and on-site ground and aerial damage surveys, this work aims to reveal the weather phenomena-especially the wind situation-when Oriental Star capsized in the Yangtze River on June 1, 2015. Results demonstrate that the cruise ship capsized when it encountered strong winds at speeds of at least 31 m s-1 near the apex of a bow echo embedded in a squall line. As suggested by the fallen trees within a 2-km radius around the wreck location, such strong winds were likely caused by microburst straight-line wind and/or embedded small vortices, rather than tornadoes.

Ultrasoft, highly deformable microgels.

Microgels are colloidally stable, hydrogel microparticles that have previously been used in a range of (soft) material applications due to their tunable mechanical and chemical properties. Most commonly, thermo and pH-responsive poly(N-isopropylacrylamide) (pNIPAm) microgels can be fabricated by precipitation polymerization in the presence of the co-monomer acrylic acid (AAc). Traditionally pNIPAm microgels are synthesized in the presence of a crosslinking agent, such as N,N'-methylenebisacrylamide (BIS), however, microgels can also be synthesized under 'crosslinker free' conditions. The resulting particles have extremely low (<0.5%), core-localized crosslinking resulting from rare chain transfer reactions. AFM nanoindentation of these ultralow crosslinked (ULC) particles indicate that they are soft relative to crosslinked microgels, with a Young's modulus of ∼10 kPa. Furthermore, ULC microgels are highly deformable as indicated by a high degree of spreading on glass surfaces and the ability to translocate through nanopores significantly smaller than the hydrodynamic diameter of the particles. The size and charge of ULCs can be easily modulated by altering reaction conditions, such as temperature, monomer, surfactant and initiator concentrations, and through the addition of co-monomers. Microgels based on the widely utilized, biocompatible polymer polyethylene glycol (PEG) can also be synthesized under crosslinker free conditions. Due to their softness and deformability, ULC microgels are a unique base material for a wide variety of biomedical applications including biomaterials for drug delivery and regenerative medicine.

Impacts of using an ensemble Kalman filter on air quality simulations along the California-Mexico border region during Cal-Mex 2010 field campaign.

The purpose of this study is to investigate the impact of using an ensemble Kalman filter (EnKF) on air quality simulations in the California-Mexico border region on two days (May 30 and June 04, 2010) during Cal-Mex 2010. The uncertainties in ozone (O3) and aerosol simulations in the border area due to the meteorological initial uncertainties were examined through ensemble simulations. The ensemble spread of surface O3 averaged over the coastal region was less than 10ppb. The spreads in the nitrate and ammonium aerosols are substantial on both days, mostly caused by the large uncertainties in the surface temperature and humidity simulations. In general, the forecast initialized with the EnKF analysis (EnKF) improved the simulation of meteorological fields to some degree in the border region compared to the reference forecast initialized with NCEP analysis data (FCST) and the simulation with observation nudging (FDDA), which in turn leading to reasonable air quality simulations. The simulated surface O3 distributions by EnKF were consistently better than FCST and FDDA on both days. EnKF usually produced more reasonable simulations of nitrate and ammonium aerosols compared to the observations, but still have difficulties in improving the simulations of organic and sulfate aerosols. However, discrepancies between the EnKF simulations and the measurements were still considerably large, particularly for sulfate and organic aerosols, indicating that there are still ample rooms for improvement in the present data assimilation and/or the modeling systems.

Aggregation rate and fractal dimension of fullerene nanoparticles via simultaneous multiangle static and dynamic light scattering measurement.

The time-evolutions of nanoparticle hydrodynamic radius and aggregate fractal dimension during the aggregation of fullerene (C(60)) nanoparticles (FNPs) were measured via simultaneous multiangle static and dynamic light scattering. The FNP aggregation behavior was determined as a function of monovalent (NaCl) and divalent (CaCl(2)) electrolyte concentration, and the impact of addition of dissolved natural organic matter (humic acid) to the solution was also investigated. In the absence of humic acid, the fractal dimension decreased over time with monovalent and divalent salts, suggesting that aggregates become slightly more open and less compact as they grow. Although the aggregates become slightly more open, the magnitude of the fractal dimension suggests intermediate aggregation between the diffusion- and reaction-limited regimes. We observed different aggregation behavior with monovalent and divalent salts upon the addition of humic acid to the solution. For NaCl-induced aggregation, the introduction of humic acid significantly suppressed the aggregation rate of FNPs at NaCl concentrations lower than 150mM. In this case, the aggregation was intermediate or reaction-limited even at NaCl concentrations as high as 500mM, giving rise to aggregates with a fractal dimension of 2.0. For CaCl(2)-induced aggregation, the introduction of humic acid enhanced the aggregation of FNPs at CaCl(2) concentrations greater than about 5mM due to calcium complexation and bridging effects. Humic acid also had an impact on the FNP aggregate structure in the presence of CaCl(2), resulting in a fractal dimension of 1.6 for the diffusion-limited aggregation regime. Our results with CaCl(2) indicate that in the presence of humic acid, FNP aggregates have a more open and loose structure than in the absence of humic acid. The aggregation results presented in this paper have important implications for the transport, chemical reactivity, and toxicity of engineered nanoparticles in aquatic environments.

Thermoresponsive microgel-based materials.

With the continued development of thermoresponsive colloidal hydrogel particles, a number of groups have begun to exploit their properties to create dynamic materials self-assembled from those components. The fundamental details of how those building blocks are assembled, the component functionality, and the geometry or length-scales present in the assemblies contribute to the behavior of the resultant material. In this tutorial review, we examine recent progress in the assembly of responsive hydrogel colloids in two and three dimensions, highlighting their potential applications, especially in the domain of biotechnology.

Physical aging and phase behavior of multiresponsive microgel colloidal dispersions.

Quantitative microscopy measurements have been made on poly(N-isopropylacrylamide-co-acrylic acid) (pNIPAm-AAc) microgel dispersions as a function of time, temperature, pH, and volume fraction. These studies reveal an extreme degree of complexity in the physical aging and phase behavior of the dispersions; this complexity arises from a convolution of the system energetics at the colloidal, polymer-chain, and molecular scales. Superficially, these dispersions display the classic colloidal phases observed for spherical particles (i.e., gas, fluid, crystal, and glass). However, unlike simple repulsive hard spheres, pNIPAm-AAc dispersions are observed to evolve from a diffusive, fluidlike state immediately after being introduced into rectangular capillary tubes, to very slow crystalline or glassy phases after days or weeks of aging. In addition to this structural evolution, the free volume accessible to the microgels in crystalline or glassy phases (i.e., the cage size) decreases with time, indicating that the physical aging process does not end following assembly, but instead continues to evolve as the dispersion slowly proceeds to an equilibrium state. The temperature dependence of pNIPAm-AAc microgel swelling and how it influences the colloidal assembly was evaluated during the aging process as well. These thermal melting experiments revealed an enhancement in the thermal stability (i.e., a decrease in the influence of temperature on the phase behavior) of the assemblies during the aging process that we associate with an evolution of attractive interparticle interactions during aging. These attractive interactions dictate the time scale for assembly (aging), the final phase adopted by the dispersion, the dynamics of the final state, and the ultimate thermal stability. The culmination of these studies is the pseudoequilibrium phase behavior of pNIPAm-AAc microgel dispersions, which we present as a function of pH and volume fraction following approximately 1 month of aging. This diagram reveals highly complex dispersion characteristics that appear to be intrinsically tied to the degree of AAc protonation. In general, we find that, at pH < pK(a), the final dispersions behave in a manner that can be associated with attractive interparticle interactions, whereas at pH > pK(a), repulsive interactions appear to be dominant. These results are discussed in the context of the slow evolution of microgel swelling and attractive interaction potentials arising from reorganization and association of polymer chains via multiple weak hydrogen-bonding interactions.

Crystallization behavior of soft, attractive microgels.

The equilibrium phase behavior and the dynamics of colloidal assemblies composed of soft, spherical, colloidal particles with attractive pair potentials have been studied by digital video microscopy. The particles were synthesized by precipitation copolymerization of N-isopropylacrylamide (NIPAm), acrylic acid (AAc), and N,N'-methylene bis(acrylamide) (BIS), yielding highly water swollen hydrogel microparticles (microgels) with temperature- and pH-tunable swelling properties. It is observed that in a pH = 3.0 buffer with an ionic strength of 10 mM, assemblies of pNIPAm-AAc microgels crystallize due to a delicate balance between weak attractive and soft repulsive forces. The attractive interactions are further confirmed by measurements of the crystal melting temperatures. As the temperature of colloidal crystals is increased, the crystalline phase does not melt until the temperature is far above the lower critical solution temperature (LCST) of the microgels, in stark contrast to what is typically observed for phases formed due to purely repulsive interactions. The unusual thermal stability of pNIPAm-AAc colloidal crystals demonstrates an enthalpic origin of crystallization for these microgels.