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Previously, we have demonstrated ID1/Myc signaling is highly expressed in oxaliplatin-resistant hepatocellular carcinoma (HCC). This study sought to investigate the role of ID1/Myc signaling on immune evasion in oxaliplatin-resistant HCC.The oxaliplatin-resistant hepatocellular carcinoma cell lines (Hepa 1-6-OXA, 97H-OXA and 3B-OXA) were established and their oxaliplatin tolerance was confirmed in vitro and in vivo. The relationship between ID1/Myc and PD-L1 upregulation, polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) accumulation was explored. The underlying mechanism in which ID1/Myc signaling regulated PD-L1 expression and PMN-MDSCs accumulation was investigated in vitro and vivo.Increased ID1/Myc expressions were identified in oxaliplatin-resistant HCC and correlate with PD-L1 upregulation and PMN-MDSCs accumulation. The knockdown of Myc sensitized oxaliplatin-resistant HCC cells to oxaliplatin and resulted in a decrease of PMN-MDSCs and an increase of IFN-γID1/Myc signaling drives immune evasion in oxaliplatin-resistant HCC via PD-L1 upregulation and PMN-MDSCs recruitment. Blocking the ID1/Myc induced immune tolerance represents a promising treatment target to conquer chemoresistance in HCC.

PURPOSE: To explore novel role and molecular mechanism of a natural anti-inflammatory cytokine interleukin (IL) 37 in preventing corneal epithelial barrier disruption from hyperosmolar stress as can occur in dry eye disease. METHODS: Primary human corneal epithelial cells (HCECs) were cultured from fresh donor limbal explants. An in vitro dry eye model with hyperosmolar stress was established by switching HCECs from isosmolar (312mOsM) to hyperosmolar medium (350–500 mOsM), and some cells were treated with rhIL-37 or rhTNF-α, for different periods (2–48 h). The expression of cytokines and cathepsin S, and barrier protein integrity were evaluated by RT-qPCR, ELISA, and immunofluorescent staining with confocal microscopy. RESULTS: The integrity of epithelial barrier was significantly disrupted in HCECs exposed to hyperosmolar medium, as shown by immunofluorescent images of tight junction (TJ, ZO-1, occludin and claudin-1) and adheren junction (E-cadherin) proteins. TNF-α accentuated hyperosmolar-induced disruption of TJ barrier functional integrity whereas exposure to IL-37 blunted or even reversed these changes. Cathepsin S, encoded by CTSS gene, was found to directly disrupt epithelial barrier integrity. Interestingly, CTSS expression was significantly induced by TNF-α and hyperosmolarity, while exogenous rhIL-37 inhibited TNF-α and CTSS expression at mRNA and protein levels following hyperosmolar stress. Furthermore, rhIL-37 restored barrier protein integrity, observed in 2D and 3D confocal immunofluorescent images, in HCECs under hyperosmolar stress. CONCLUSION: Our findings demonstrate a novel signaling pathway by which anti-inflammatory cytokine IL-37 prevents corneal epithelial barrier disruption under hyperosmotic stress via suppressing TNF-α and CTSS expression. This study provides new insight into mechanisms protecting corneal barrier in dry eye disease.

The operating temperature of hydrogels, especially at low temperatures, is crucial due to their wide applicability in soft robots, sensors, and electronic skin. Hydrogels are often used at room temperature, but their performance may deteriorate at low temperatures. Therefore, it is crucial to develop hydrogels that can be used at low temperatures to expand their range of use. Herein, we have proposed a simple one-pot method to prepare a frost-resistant (-70 °C) and conductive hydrogel consisting of a glycerol (Gly)-water binary solvent. We have added tannic acid (TA)-coated carboxymethylated cellulose nanofibrils (CMCNFs) to poly (vinyl alcohol) (PVA) as a functional filler to improve the hydrogel's mechanical properties. The introduction of sulfonated carbon nanotubes (SCNT) has provided the hydrogel with high conductivity (0.1 S/m), strain sensitivity (gauge factor of 3.76), and cyclic stability (1600 cycles). Due to the strong hydrogen bonding and physical entanglement effects between the components, the hydrogel exhibied excellent tensile properties (297 %), high toughness (0.44 MJ/m

A new tetraphenylethylene-cyclodextrin (TPE-CD) conjugate with a linkage composed of long triethylene glycol chain and triazole ring on the CD rim has been designed and synthesized. The TPE-CD conjugate exists in a stretched form in DMSO and enhances its fluorescence after addition of a small amount of water due to aggregation-induced emission (AIE) effect. However, in the presence of a large amount of water, the TPE unit will enter the cyclodextrin cavity to form a folded self-inclusion compound. In the self-inclusion compound, not only nitrogen-containing pseudo-crown ether is formed but also arouses photo-induced electron transfer (PET) process from nitrogen atoms of triazole ring to TPE unit and quenches the fluorescence although more aggregation occurs in more water. This is the first finding that TPE-macrocycle conjugate can form pseudo-crown ether and has both the AIE phenomenon and the PET effect. Interestingly, only mercury ion arouses the fluorescence recover of the self-inclusion compound by entering the pseudo-crown ether cavity and blocking the PET process by binding to the nitrogen atoms, while other tested metal ions almost have no effect on the fluorescence. Therefore, the TPE-CD conjugate can be used for the highly selective fluorescence "Turn-On" detection of Hg2+.

Breast cancer is prone to relapse and metastasize to many vital organs, contributing to most of the breast cancer-related death and accentuating the importance of systematic identification of key factors regulating the metastasis of breast cancer. In this study, we performed a genome-wide CRISPR/Cas9 knock out screen in an orthotopic murine model of breast cancer for essential genes monitoring the progression and metastasis of breast cancer. We found one member of the zinc finger protein (ZNF) family, i.e., ZNF319, was among the top candidate genes. We further confirmed the lower expression of ZNF319 in the tumor tissue of breast cancer patients by analyzing tissue sections with IHC staining and TCGA database. Consistently, higher expression of ZNF319 correlates with better clinical outcome in almost all subtypes of breast cancer. Moreover, knocking down or overexpressing ZNF319 in breast cancer cells dramatically affects the breast cancer growth and metastasis capacity both in vitro and in vivo, suggesting ZNF319 functions as a strong suppressor of breast cancer progression. Lastly, the transcriptome analysis on ZNF319-silenced breast cancer cells shows that ZNF319 is involved in multiple crucial signaling pathways and biological processes, especially in cell cycle and proliferation. GO and KEGG analyses of our RNA-seq results reveal the up-regulation of E2F and G2/M related genes in ZNF319-silenced cells, suggesting that ZNF319 monitors the cell cycle during the breast cancer progression through the regulation of the E2F target genes and G2/M checkpoint. In summary, our study identifies ZNF319 as a novel metastasis suppressor gene arresting tumor cell cycle in breast cancer and thus presents a novel potential therapeutic target for breast cancer treatment.

Gradient-based algorithms are commonly used for training radial basis function neural network (RBFNN). However, it is still difficult to avoid vanishing gradient to improve the learning performance in the training process. For this reason, in this paper, an accelerated second-order learning (ASOL) algorithm is developed to train RBFNN. First, an adaptive expansion and pruning mechanism (AEPM) of gradient space, based on the integrity and orthogonality of hidden neurons, is designed. Then, the effective gradient information is constantly added to gradient space and the redundant gradient information is eliminated from gradient space. Second, with AEPM, the neurons are generated or pruned accordingly. In this way, a self-organizing RBFNN (SORBFNN) which reduces the structure complexity and improves the generalization ability is obtained. Then, the structure and parameters in the learning process can be optimized by the proposed ASOL-based SORBFNN (ASOL-SORBFNN). Third, some theoretical analyses including the efficiency of the proposed AEPM on avoiding the vanishing gradient and the stability of SORBFNN in the process of structural adjustment are given, then the successful application of the proposed ASOL-SORBFNN is guaranteed. Finally, to illustrate the advantages of the proposed ASOL-SORBFNN, several experimental studies are examined. By comparing with other existing approaches, the results show that ASOL-SORBFNN performs well in terms of both learning speed and prediction accuracy.

In permafrost peatlands, the degradation of permafrost soil can raise soil temperature and alter moisture conditions, which increases the rate of loss of soil organic carbon (SOC). Here we selected three typical permafrost types that have very different active layer thicknesses but with soil originating from the same vegetation and which exist under comparable climatic conditions in the Da Xing’an mountain range: continuous permafrost, island permafrost, and island melting permafrost. To quantify the relative importance of control elements on SOC stabilization in these different permafrost types, we used correlation analysis to assess the relationship between organic carbon, physical and chemical properties and microorganisms, and explored the contribution of these factors to the accumulation of organic carbon. This study shows that the interaction between clay or silt, iron oxides and microorganisms have an important influence on the stability of organic carbon in permafrost peatlands.

Vision impairment (VI) is associated with poor quality of life and increased risk of falls. Few prospective data are available on Asians. This study investigates the longitudinal impact of VI and the major eye diseases on mortality risk in Asians.Prospective cohort study with meta-analysis.We conducted a multi-ethnic prospective study of adults (40-80 years old) in the Singapore Epidemiology of Eye Diseases Study (baseline: 2004-2011). All-cause mortality was obtained from the National Death Registry until May 2017. VI was defined by best-corrected visual acuity (BCVA)20/40 in the better eye. Major eye diseases were assessed using standard protocols. We examined associations using multivariate-adjusted Cox proportional hazards regression models. Finally, we conducted a meta-analysis of the associations between VI and mortality.Of 9,986 participants, 1,210 deaths occurred (12.1%) over a median follow-up of 8.8 years. Compared to participants with normal vision, persons with VI had increased risk of mortality (hazards ratio [HR]: 1.53; 95% confidence interval [CI:] 1.30-1.81) in multivariate models. In ethnicity-specific analyses, this association was significant across Chinese (HR: 1.63; 95% CI: 1.08-2.48); Malays (HR: 1.31; 95% CI: 1.06-1.62); and Indians (HR: 2.25; 95% CI: 1.61-3.15). Cataract, under-corrected refractive errors (URE), and diabetic retinopathy (DR) were significantly associated with mortality (HRs: 1.30, 1.22, and 1.54, respectively). In a meta-analysis of 12 studies including 58,034 persons, VI was associated with 30% increased risk of mortality (HR: 1.3; 95% CI: 1.2-1.5).In this multi-ethnic Asian population, VI and preventable eye conditions (cataract, URE, and DR) were associated with mortality, emphasizing the need for early detection and intervention to prevent and treat VI and major eye diseases.