BPIFB1, Serving as a Downstream Effector of EBV-miR-BART4, Blocks Immune Escape of Nasopharyngeal Carcinoma via Inhibiting PD-L1 Expression.

Nasopharyngeal carcinoma (NPC) is one of the most common tumors of head and neck in the Southeast Asia. PD-L1-dependent immune escape plays a critical role involved in NPC development. BPIFB1 has previously reported to take tumor-suppressive actions on NPC cell proliferation and migration. Nonetheless, the function of BPIFB1 in immune escape remains largely elusive. Expression pattern on mRNA and protein levels of target genes in NPC patients' samples and cell lines were examined by qRT-PCR, western blot, and immunohistochemistry staining, respectively. The assessment of CD8+ T-cell apoptosis and expression was determined by flow cytometry. Molecular interactions were verified using chromatin immunoprecipitation (ChIP) and luciferase reporter assay. BPIFB1 was downregulated in NPC tumor tissues, exhibiting a negative correlation of PD-L1. Overexpression of BPIFB1 significantly inhibited the expression of PD-L1, suppressing the apoptosis and enhancing the expression of CD8+ T cells. Mechanistically, BPIFB1 was found to repress the expression of STAT1, which was identified to be an upstream activator of PD-L1. Furthermore, the EBV-encoded miR-BART4 overexpressed in NPC cells could directly target and inhibit BPIFB1. This study provided a comprehensive understanding of the molecular mechanism for the upstream and downstream pathway of BPIFB1 related with immune escape, indicating a novel approach for the treatment of NPC.

Fe-loaded alginate hydrogel beads activating peroxymonosulfate for enhancing anaerobic fermentation of waste activated sludge: Performance and potential mechanism.

The recovery of volatile fatty acids (VFAs) through anaerobic fermentation (AF) is usually restricted by the poor biodegradability of waste activated sludge (WAS). This study proposed a novel strategy, i.e. peroxymonosulfate (PMS) activated by Fe-loaded sodium alginate hydrogel beads (Fe-SA), to enhance AF performance. Experimental results demonstrated that the as-synthesized Fe-SA and PMS co-pretreatment synergistically enhanced WAS solubilization and VFAs production. The maximal VFAs yield of 2013 mg COD/L was achieved at the Fe-SA dosage of 4.0 mM/g TSS, which was 93.7% higher than that with sole PMS addition and 8.82 times higher than that of the control. Mechanistic studies elucidated that the generation of reactive radicals such as SO4•- and •OH from PMS was greatly induced by Fe-SA, which contributed to WAS disintegration and degradation of refractory compounds. Additionally, analysis of the key enzyme activities indicated that the Fe-SA could strengthen biological hydrolysis and acidogenesis of sludge during AF. Microbial analysis illustrated that Fe-SA evidently improved the abundances of fermentative microorganisms as well as functional gene expression via creating a favorable environment for microbial growth. This study demonstrated the applicable potential of Fe-SA hydrogel beads activating PMS for VFAs production and provides an important reference for developing advanced oxidation processes-based application in AF.

Tuning 2D magnetism in Fe3+XGeTe2 films by element doping.

Two-dimensional (2D) ferromagnetic materials have been discovered with tunable magnetism and orbital-driven nodal-line features. Controlling the 2D magnetism in exfoliated nanoflakes via electric/magnetic fields enables a boosted Curie temperature (T C) or phase transitions. One of the challenges, however, is the realization of high T C 2D magnets that are tunable, robust and suitable for large scale fabrication. Here, we report molecular-beam epitaxy growth of wafer-scale Fe3+XGeTe2 films with T C above room temperature. By controlling the Fe composition in Fe3+XGeTe2, a continuously modulated T C in a broad range of 185-320 K has been achieved. This widely tunable T C is attributed to the doped interlayer Fe that provides a 40% enhancement around the optimal composition X = 2. We further fabricated magnetic tunneling junction device arrays that exhibit clear tunneling signals. Our results show an effective and reliable approach, i.e. element doping, to producing robust and tunable ferromagnetism beyond room temperature in a large-scale 2D Fe3+XGeTe2 fashion.

The Hippo Pathway Effector Transcriptional Co-activator With PDZ-Binding Motif Correlates With Clinical Prognosis and Immune Infiltration in Colorectal Cancer.

The transcriptional co-activator with PDZ-binding motif (TAZ) is a downstream effector of the Hippo pathway. It has been identified as an oncogene in certain tumor types; however, the function and role of TAZ in colorectal cancer (CRC) has not been illustrated. Here, we aimed to analyze the expression and role of TAZ in CRC. In this study, we investigated the expression level of TAZ in 127 CRC and matched adjacent normal tissues by immunohistochemistry (IHC) and analyzed its correlation with clinicopathological characteristics in CRC. Moreover, we further analyzed the role of TAZ in the CRC-associated immunology using integrative bioinformatic analyses. The cBioPortal and WebGestalt database were used to analyze the co-expressed genes and related pathways of TAZ in CRC by gene ontology (GO) and KEGG enrichment analyses. Meanwhile, the correlations between TAZ and the infiltrating immune cells and gene markers were analyzed by TIMER database. Our study revealed that TAZ expression is higher in CRC tissues than in matched adjacent non-tumor tissues. In addition, CRC patients with higher TAZ expression demonstrated poor overall survival (OS) and recurrent-free survival rates as compared to CRC patients with lower expression of TAZ. Furthermore, the TAZ expression was identified to closely associate with the immune infiltration of CD4 + T, CD8 + T, and B cells. Taken together, our findings suggest that TAZ may serve as a promising prognostic biomarker and therapeutic target in CRC.

Clinical Significance and Integrative Analysis of the SMC Family in Hepatocellular Carcinoma.

Worldwide, hepatocellular carcinoma (HCC) is one of the most malignant cancers with poor prognosis. The structural maintenance of chromosomes (SMC) gene family has been shown to play important roles in human cancers. Nevertheless, the role of SMC members in HCC is not well-understood. In this study, we comprehensively explored the role of the SMC family in HCC using a series of bioinformatic analysis tools. Studies have demonstrated that the mRNA expression levels of SMC1A, SMC1B, SMC2, SMC4, and SMC6 are significantly overexpressed in HCC, and the protein levels of SMC1A, SMC2, SMC3, SMC4, SMC5, and SMC6 are similarly elevated. Moreover, HCC patients with high SMC2 and SMC4 expression levels exhibit poor survival. Using KEGG and GO analyses, we analyzed the enrichment of gene expression in the biological functions and pathways of the SMC family in HCC. Immune infiltration analysis revealed that the expression of the SMC family is closely associated with B cells, CD4+ T cells, CD8+ T cells, macrophages, neutrophils, and DCs. In conclusion, our findings will enhance a more thorough understanding of the SMC family in HCC progression and provide new directions for the diagnosis and treatment of HCC in the future.

RBP-J promotes cell growth and metastasis through regulating miR-182-5p-mediated Tiam1/Rac1/p38 MAPK axis in colorectal cancer.

BACKGROUND: RBP-J is involved in number of cellular processes. However, the potential mechanisms of RBP-J on colorectal cancer (CRC) development have not been clearly defined. In this study, we aimed to investigate the role and molecular mechanism of RBP-J in CRC. METHODS: The expression levels of RBP-J and Tiam1 in CRC tissues and cells were evaluated by RT-qPCR or western blot. RBP-J was knocked down with sh-RBP-J or overexpressed by pcDNA3.1-RBP-J in CRC cells. Cell proliferation, migration and invasion abilities were analyzed by MTT, wound healing, and transwell assay, respectively. CHIP-qPCR, RIP and dual luciferase reporter assays were performed to confirm the interaction between miR-182-5p and RBP-J or Tiam1. Expression levels of p-p38 MAPK, p38 MAPK, Slug-1, Twist1 and MMP-9 were analyzed by western blot. G-LISA test was used to detect Rac1 activity. RESULTS: Our results showed that the expression of RBP-J and Tiam1 was significantly up-regulated in CRC tissues and cells. RBP-J overexpression promoted proliferation, migration and invasion of CRC cells. Moreover, RBP-J was found to directly target miR-182-5p promoter and positively regulate the Tiam1/Rac1/p38 MAPK signaling pathway in CRC cells. It was also proved that miR-182-5p can bind Tiam1 directly. Furthermore, experiments revealed that RBP-J could promote CRC cell proliferation, migration and invasion via miR-182-5p-mediated Tiam1/Rac1/p38 MAPK axis. In addition, knockdown of RBP-J reduced tumor growth and metastasis in CRC mice. CONCLUSION: RBP-J regulates CRC cell growth and metastasis through miR-182-5p mediated Tiam1/Rac1/p38 MAPK signaling pathway, implying potential novel therapeutic targets for CRC patients.

Expression and Clinical Significance of Lactate Dehydrogenase A in Colon Adenocarcinoma.

Lactate dehydrogenase A (LDHA) is an important glycolytic enzyme that promotes glycolysis and plays a crucial role in cancer cell invasion and immune infiltration. However, the relevance of LDHA in colon adenocarcinoma (COAD) remains unclear. In this study, we analyzed the correlation between the expression of LDHA and clinicopathological characteristics in COAD using immunohistochemistry analysis, and then used integrative bioinformatics analyses to further study the function and role of LDHA in COAD. We found that LDHA was highly expressed in COAD tissues compared with adjacent normal tissues, and that COAD patients with high LDHA expression levels showed poor survival. In addition, LDHA expression was closely associated with the immune infiltrating levels of CD8+ T cells, neutrophils, and dendritic cells. Our findings highlight the potential role of LDHA in the tumorigenesis and prognosis of COAD. Furthermore, our results indicate that COAD is a novel immune checkpoint in the diagnosis and treatment of COAD.

The Emerging Landscape of Long Non-Coding RNAs in Colorectal Cancer Metastasis.

Colorectal cancer (CRC) is one of the most common gastrointestinal cancers, with extremely high rates of morbidity and mortality. The main cause of death in CRC is distant metastasis; it affects patient prognosis and survival and is one of the key challenges in the treatment of CRC. Long non-coding RNAs (lncRNAs) are a group of non-coding RNA molecules with more than 200 nucleotides. Abnormal lncRNA expression is closely related to the occurrence and progression of several diseases, including cancer. Recent studies have shown that numerous lncRNAs play pivotal roles in the CRC metastasis, and reversing the expression of these lncRNAs through artificial means can reduce the malignant phenotype of metastatic CRC to some extent. This review summarizes the major mechanisms of lncRNAs in CRC metastasis and proposes lncRNAs as potential therapeutic targets for CRC and molecular markers for early diagnosis.

LncRNA FTX Promotes Colorectal Cancer Cells Migration and Invasion by miRNA-590-5p/RBPJ Axis.

Colorectal cancer (CRC) is one of the most lethal human cancers all over the world. Moreover, it ranks fourth for cancer-related deaths among males. Although many efforts have been made to cure CRC, the effect remains limited. It has been reported that lncRNA five prime to Xist (FTX) was upregulated in CRC. However, the mechanism by which lncRNA FTX regulates the progression of CRC remains largely unknown. In this study, qRT-PCR was performed to detect the expression of FTX, miR-590-5p and Recombination signal binding protein for immunoglobulin kappa J region (RBPJ) in CRC tissues or cells. Protein expression in cells was measured by western blot. MTT assay was used to test the cell viability. Moreover, transwell was performed to examine the cell migration and invasion. Luciferase report assay was performed to verify the relation between miR-590-5p and FTX or RBPJ. It was found that FTX was upregulated in CRC tissues and cells. Knockdown of FTX or overexpression of miR-590-5p can inhibit the proliferation, migration, and invasion of CRC cells. Besides, silencing of FTX could inhibit the expression of migration and invasion-related proteins in CRC cells. Meanwhile, miR-590-5p was the target of FTX, and RBPJ was the direct target of miR-590-5p. Inhibition of miR-590-5p could reverse the inhibitory effect of FTX on the progression of CRC. These findings suggested that knockdown of FTX could inhibit the tumorigenesis of CRC in vitro, which may serve as a potential novel strategy for treatment of CRC.

The emerging role of super enhancer-derived noncoding RNAs in human cancer.

Super enhancers (SEs) are large clusters of adjacent enhancers that drive the expression of genes which regulate cellular identity; SE regions can be enriched with a high density of transcription factors, co-factors, and enhancer-associated epigenetic modifications. Through enhanced activation of their target genes, SEs play an important role in various diseases and conditions, including cancer. Recent studies have shown that SEs not only activate the transcriptional expression of coding genes to directly regulate biological functions, but also drive the transcriptional expression of non-coding RNAs (ncRNAs) to indirectly regulate biological functions. SE-derived ncRNAs play critical roles in tumorigenesis, including malignant proliferation, metastasis, drug resistance, and inflammatory response. Moreover, the abnormal expression of SE-derived ncRNAs is closely related to the clinical and pathological characterization of tumors. In this review, we summarize the functions and roles of SE-derived ncRNAs in tumorigenesis and discuss their prospective applications in tumor therapy. A deeper understanding of the potential mechanism underlying the action of SE-derived ncRNAs in tumorigenesis may provide new strategies for the early diagnosis of tumors and targeted therapy.

The function and mechanism of circular RNAs in gastrointestinal tumours.

Gastrointestinal tumours are tumours that originate in the digestive tract and have extremely high morbidity and mortality. The main categories include: oesophageal, gastric, and colorectal cancers. Circular RNAs are a new class of non-coding RNAs with a covalent closed-loop structure without a 5' cap or a 3' poly A tail, which can encode a small amount of polypeptide. Recent studies have shown that circRNAs are involved in multiple biological processes during the development of gastrointestinal tumours including proliferation, invasion and metastasis, radio- and chemoresistance, and inflammatory responses. Also, the clinical and pathological characteristics of the patient, such as staging and lymph node metastasis, are closely associated with the expression level of circRNAs. Further investigation of the function and the role of circRNAs in the development of gastrointestinal tumours will provide new directions for its clinical diagnosis and treatment.

The impact of technology-environmental innovation on CO2 emissions in China's transportation sector.

Along with the development of urbanization and informationization, an increasing attention has been attracted to CO2 emissions of China's transportation sector and its influencing factors. Such researches mainly utilize single indicator or two indicators to represent technology process. This research aims to verify the influence of technology-environmental innovation indicator system on CO2 emissions of China's transportation sector by decoupling elasticity and econometric model. We firstly recognize the decoupling status of CO2 emissions of China's transportation sector from social economic development and aggregate China's 30 provinces into two groups according to the varied decoupling status, namely expansive coupling and weak decoupling groups. Then, we develop a relatively comprehensive technology-environmental innovation indicator system to measure technology process. Finally, the multi-region comparison of emission drivers is studied among overall China and the two groups. The result shows that the decoupling elasticity of China's transportation has experienced an evolution process trending to desired development status and all the provinces have experienced expansive coupling and weak decoupling from 2001 to 2016, except Qinghai. Innovation performance indicators exert most important influence on the CO2 emissions of transportation sector. Finally, the influences of technology-environmental innovation indicators are similar across groups with different magnitude, suggesting that common but differentiated strategies should be provided when mitigating CO2 emissions with technology process. Graphical abstract.

Relationship between relative deprivation and health of Hainan Island residents: mediating effect of negative health behaviors.

Despite extensive evidence of the direct impact of relative deprivation on health, the mediating role of tobacco, alcohol and betel nuts in this impact has been largely ignored. This study aimed to verify whether these negative health behaviors are mediating factors for relative deprivation and health according to the mediating effect concept. Data from the Hainan Island Residents Health Interview Survey in 2017 were used. Variables including age, marital status, educational level, chronic diseases and area of residence were controlled for in multivariate analysis with separate sex analyses. Mediating effects of smoking, alcohol drinking and betel nut chewing, and whether the effects were complete or partial, were analyzed by logistic regression analysis. Smoking, alcohol drinking and betel nut chewing had a significant mediating effect in men, but not in women; however, alcohol drinking and betel nut chewing had similar, significant complete mediation in both sexes. Dissatisfaction following relative deprivation due to uneven income distribution may be relieved through these negative health behaviors. Therefore, better medical resources should be provided to improve residents' health and the impact of income inequality on health, particularly the growing gap between the rich and poor, should be addressed.

Two-dimensional ferromagnetic superlattices.

Mechanically exfoliated two-dimensional ferromagnetic materials (2D FMs) possess long-range ferromagnetic order and topologically nontrivial skyrmions in few layers. However, because of the dimensionality effect, such few-layer systems usually exhibit much lower Curie temperature (T C) compared to their bulk counterparts. It is therefore of great interest to explore effective approaches to enhance their T C, particularly in wafer-scale for practical applications. Here, we report an interfacial proximity-induced high-T C 2D FM Fe3GeTe2 (FGT) via A-type antiferromagnetic material CrSb (CS) which strongly couples to FGT. A superlattice structure of (FGT/CS)n, where n stands for the period of FGT/CS heterostructure, has been successfully produced with sharp interfaces by molecular-beam epitaxy on 2-inch wafers. By performing elemental specific X-ray magnetic circular dichroism (XMCD) measurements, we have unequivocally discovered that T C of 4-layer Fe3GeTe2 can be significantly enhanced from 140 K to 230 K because of the interfacial ferromagnetic coupling. Meanwhile, an inverse proximity effect occurs in the FGT/CS interface, driving the interfacial antiferromagnetic CrSb into a ferrimagnetic state as evidenced by double-switching behavior in hysteresis loops and the XMCD spectra. Density functional theory calculations show that the Fe-Te/Cr-Sb interface is strongly FM coupled and doping of the spin-polarized electrons by the interfacial Cr layer gives rise to the T C enhancement of the Fe3GeTe2 films, in accordance with our XMCD measurements. Strikingly, by introducing rich Fe in a 4-layer FGT/CS superlattice, T C can be further enhanced to near room temperature. Our results provide a feasible approach for enhancing the magnetic order of few-layer 2D FMs in wafer-scale and render opportunities for realizing realistic ultra-thin spintronic devices.

Proximity-induced surface superconductivity in Dirac semimetal Cd3As2.

Cd3As2 is a three-dimensional Dirac semimetal with separated Dirac points in momentum space. In spite of extensive transport and spectroscopic studies on its exotic properties, the evidence of superconductivity in its surface states remains elusive. Here, we report the observation of proximity-induced surface superconductivity in Nb/Cd3As2 hybrid structures. Our four-terminal transport measurement identifies a pronounced proximity-induced pairing gap (gap size comparable to Nb) on the surfaces, which exhibits a flat conductance plateau in differential conductance spectra, consistent with our theoretical simulations. The surface supercurrent from Nb/Cd3As2/Nb junctions is also achieved with a Fraunhofer/SQUID-like pattern under out-of-plane/in-plane magnetic fields, respectively. The resultant mapping shows a predominant distribution on the top and bottom surfaces as the bulk carriers are depleted, which can be regarded as a higher dimensional analog of edge supercurrent in two-dimensional quantum spin Hall insulators. Our study provides the evidence of surface superconductivity in Dirac semimetals.

Ultrahigh conductivity in Weyl semimetal NbAs nanobelts.

In two-dimensional (2D) systems, high mobility is typically achieved in low-carrier-density semiconductors and semimetals. Here, we discover that the nanobelts of Weyl semimetal NbAs maintain a high mobility even in the presence of a high sheet carrier density. We develop a growth scheme to synthesize single crystalline NbAs nanobelts with tunable Fermi levels. Owing to a large surface-to-bulk ratio, we argue that a 2D surface state gives rise to the high sheet carrier density, even though the bulk Fermi level is located near the Weyl nodes. A surface sheet conductance up to 5-100 S per □ is realized, exceeding that of conventional 2D electron gases, quasi-2D metal films, and topological insulator surface states. Corroborated by theory, we attribute the origin of the ultrahigh conductance to the disorder-tolerant Fermi arcs. The evidenced low-dissipation property of Fermi arcs has implications for both fundamental study and potential electronic applications.

Girdin (GIV) Expression as a Prognostic Marker of Recurrence in Mismatch Repair-Proficient Stage II Colon Cancer.

PURPOSE: Prognostic markers that identify patients with stage II colon cancers who are at the risk of recurrence are essential to personalize therapy. We evaluated the potential of GIV/Girdin as a predictor of recurrence risk in such patients. EXPERIMENTAL DESIGN: Expression of full-length GIV was evaluated by IHC using a newly developed mAb together with a mismatch repair (MMR)-specific antibody panel in three stage II colon cancer patient cohorts, that is, a training (n = 192), test (n = 317), and validation (n = 181) cohort, with clinical follow-up data. Recurrence risk stratification models were established in the training cohort of T3, proficient MMR (pMMR) patients without chemotherapy and subsequently validated. RESULTS: For T3 pMMR tumors, GIV expression and the presence of lymphovascular invasion (LVI) were the only factors predicting recurrence in both training (GIV: HR, 2.78, P = 0.013; LVI: HR, 2.54, P = 0.025) and combined test and validation (pooled) cohorts (GIV: HR, 1.85, P = 0.019; LVI: HR, 2.52, P = 0.0004). A risk model based on GIV expression and LVI status classified patients into high- or low-risk groups; 3-year recurrence-free survival was significantly lower in the high-risk versus low-risk group across all cohorts [Training: 52.3% vs. 84.8%; HR, 3.74, 95% confidence interval (CI), 1.50-9.32; Test: 85.9% vs. 97.9%, HR, 7.83, 95% CI, 1.03-59.54; validation: 59.4% vs. 84.4%, HR, 3.71, 95% CI, 1.24-11.12]. CONCLUSIONS: GIV expression status predicts recurrence risk in patients with T3 pMMR stage II colon cancer. A risk model combining GIV expression and LVI status information further enhances prediction of recurrence. Further validation studies are warranted before GIV status can be routinely included in patient management algorithms. Clin Cancer Res; 22(14); 3488-98. ©2016 AACR.

Separation of top and bottom surface conduction in Bi2Te3 thin films.

Quantum spin Hall (QSH) systems are insulating in the bulk with gapless edges or surfaces that are topologically protected and immune to nonmagnetic impurities or geometric perturbations. Although the QSH effect has been realized in the HgTe/CdTe system, it has not been accomplished in normal 3D topological insulators. In this work, we demonstrate a separation of two surface conductions (top/bottom) in epitaxially grown Bi(2)Te(3) thin films through gate dependent Shubnikov-de Haas (SdH) oscillations. By sweeping the gate voltage, only the Fermi level of the top surface is tuned while that of the bottom surface remains unchanged due to strong electric field screening effects arising from the high dielectric constant of Bi(2)Te(3). In addition, the bulk conduction can be modulated from n- to p-type with a varying gate bias. Our results on the surface control hence pave a way for the realization of QSH effect in topological insulators which requires a selective control of spin transports on the top/bottom surfaces.

Defect-free <110> zinc-blende structured InAs nanowires catalyzed by palladium.

We report the epitaxial growth of defect-free zinc-blende structured InAs nanowires on GaAs{111}(B) substrates using palladium catalysts in a metal-organic chemical vapor deposition reactor. Through detailed morphological, structural, and chemical characterizations using electron microscopy, it is found that these defect-free InAs nanowires grew along the <1[combining overline]1[combining overline]0> directions with four low-energy {111} faceted side walls and {1[combining overline]1[combining overline]3[combining overline]} nanowire/catalyst interfaces. It is anticipated that these defect-free <1[combining overline]1[combining overline]0> nanowires benefit from the fact that the nanowire/catalyst interfaces does not contain the {111} planes, and the nanowire growth direction is not along the <111> directions. This study provides an effective approach to control the crystal structure and quality of epitaxial III-V nanowires.

Quantitative study of GaAs nanowires catalyzed by Au film of different thicknesses.

In this letter, we quantitatively investigated epitaxial GaAs nanowires catalyzed by thin Au films of different thicknesses on GaAs (111)B substrates in a metal-organic chemical vapor deposition reactor. Prior to nanowire growth, the de-wetting of Au thin films to form Au nanoparticles on GaAs (111)B in AsH3 ambient at different temperatures is investigated. It is found that with increasing film thickness, the size of the Au nanoparticles increases while the density of the nanoparticles reduces. Furthermore, higher annealing temperature produces larger Au nanoparticles for a fixed film thickness. As expected, the diameters and densities of the as-grown GaAs nanowires catalyzed by these thin Au films reflect these trends.