Steam-Assisted Selective CO2 Hydrogenation to Ethanol over Ru-In Catalysts.

Multicomponent catalysts can be designed to synergistically combine reaction intermediates at interfacial active sites, but restructuring makes systematic control and understanding of such dynamics challenging. We here unveil how reducibility and mobility of indium oxide species in Ru-based catalysts crucially control the direct, selective conversion of CO2 to ethanol. When uncontrolled, reduced indium oxide species occupy the Ru surface, leading to deactivation. With the addition of steam as a mild oxidant and using porous polymer layers to control In mobility, Ru-In2O3 interface sites are stabilized, and ethanol can be produced with superior overall selectivity (70%, rest CO). Our work highlights how engineering of bifunctional active ensembles enables cooperativity and synergy at tailored interfaces, which unlocks unprecedented performance in heterogeneous catalysts.

Revealing Structural Evolution of Nickel Phosphide-Iron Oxide Core-Shell Nanocatalysts in Alkaline Medium for the Oxygen Evolution Reaction.

Metal phosphide-containing materials have emerged as a potential candidate of nonprecious metal-based catalysts for alkaline oxygen evolution reaction (OER). While it is known that metal phosphide undergoes structural evolution, considerable debate persists regarding the effects of dynamics on the surface activation and morphological stability of the catalysts. In this study, we synthesize NiP x -FeO x core-shell nanocatalysts with an amorphous NiP x core designed for enhanced OER activity. Using ex situ X-ray absorption spectroscopy, we elucidate the local structural changes as a function of the cyclic voltammetry cycles. Our studies suggest that the presence of corner-sharing octahedra in the FeO x shell improves structural rigidity through interlayer cross-linking, thereby inhibiting the diffusion of OH-/H2O. Thus, the FeO x shell preserves the amorphous NiP x core from rapid oxidation to Ni3(PO4)2 and Ni(OH)2. On the other hand, the incorporation of Ni from the core into the FeO x shell facilitates absorption of hydroxide ions for OER. As a result, Ni/Fe(OH) x at the surface oxidizes to the active γ-(oxy)hydroxide phase under the applied potentials, promoting OER. This intriguing synergistic behavior holds significance as such a synthetic route involving the FeO x shell can be extended to other systems, enabling manipulation of surface adsorption and diffusion of hydroxide ions. These findings also demonstrate that nanomaterials with core-shell morphologies can be tuned to leverage the strength of each metallic component for improved electrochemical activities.

Unlocking the unfolded structure of ubiquitin: Combining time-resolved x-ray solution scattering and molecular dynamics to generate unfolded ensembles.

The unfolding dynamics of ubiquitin were studied using a combination of x-ray solution scattering (XSS) and molecular dynamics (MD) simulations. The kinetic analysis of the XSS ubiquitin signals showed that the protein unfolds through a two-state process, independent of the presence of destabilizing salts. In order to characterize the ensemble of unfolded states in atomic detail, the experimental XSS results were used as a constraint in the MD simulations through the incorporation of x-ray scattering derived potential to drive the folded ubiquitin structure toward sampling unfolded states consistent with the XSS signals. We detail how biased MD simulations provide insight into unfolded states that are otherwise difficult to resolve and underscore how experimental XSS data can be combined with MD to efficiently sample structures away from the native state. Our results indicate that ubiquitin samples unfolded in states with a high degree of loss in secondary structure yet without a collapse to a molten globule or fully solvated extended chain. Finally, we propose how using biased-MD can significantly decrease the computational time and resources required to sample experimentally relevant nonequilibrium states.

Dynamic structural evolution of MgO-supported palladium catalysts: from metal to metal oxide nanoparticles to surface then subsurface atomically dispersed cations.

Supported noble metal catalysts, ubiquitous in chemical technology, often undergo dynamic transformations between reduced and oxidized states-which influence the metal nuclearities, oxidation states, and catalytic properties. In this investigation, we report the results of in situ X-ray absorption spectroscopy, scanning transmission electron microscopy, and other physical characterization techniques, bolstered by density functional theory, to elucidate the structural transformations of a set of MgO-supported palladium catalysts under oxidative treatment conditions. As the calcination temperature increased, the as-synthesized supported metallic palladium nanoparticles underwent oxidation to form palladium oxides (at approximately 400 °C), which, at approximately 500 °C, were oxidatively fragmented to form mixtures of atomically dispersed palladium cations. The data indicate two distinct types of atomically dispersed species: palladium cations located at MgO steps and those embedded in the first subsurface layer of MgO. The former exhibit significantly higher (>500 times) catalytic activity for ethylene hydrogenation than the latter. The results pave the way for designing highly active and stable supported palladium hydrogenation catalysts with optimized metal utilization.

Atomically Dispersed Ru-doped Ti4O7 Electrocatalysts for Chlorine Evolution Reaction with a Universal Activity.

Chlorine has been supplied by the chlor-alkali process that deploys dimensionally stable anodes (DSAs) for the electrochemical chlorine evolution reaction (ClER). The paramount bottlenecks have been ascribed to an intensive usage of precious elements and inevitable competition with the oxygen evolution reaction. Herein, a unique case of Ru2+-O4 active motifs anchored on Magnéli Ti4O7 (Ru-Ti4O7) via a straightforward wet impregnation and mild annealing is reported. The Ru-Ti4O7 performs radically active ClER with minimal deployment of Ru (0.13 wt%), both in 5 m NaCl (pH 2.3) and 0.1 m NaCl (pH 6.5) electrolytes. Scanning electrochemical microscopy demonstrates superior ClER selectivity on Ru-Ti4O7 compared to the DSA. Operando X-ray absorption spectroscopy and density functional theory calculations reveal a universally active ClER (over a wide range of pH and [Cl-]), through a direct adsorption of Cl- on Ru2+-O4 sites as the most plausible pathway, together with stabilized ClO* at low [Cl-] and high pH.

Impact of Prospero Homeobox-1 (PROX-1) οn the Oncogenic Phenotypes of Hepatocellular Carcinoma Cells.

BACKGROUND/AIM: Transcriptional factor prospero homeobox-1 (PROX-1) is crucial for the embryonic development of various organs and cell fate specification. It exhibits either an oncogenic or tumor suppressive activity depending on cancer types. However, the relationship between PROX-1 and hepatocellular carcinoma (HCC) remains obscure. This study was conducted to investigate the effect of PROX-1 on the invasive and oncogenic phenotypes of human HCC cells. MATERIALS AND METHODS: The effect of PROX-1 on tumor cell behavior was investigated by using a pcDNA-myc vector and a small interfering RNA in HepG2 and Huh7 human HCC cell lines. Flow cytometry, migration, invasion, proliferation, and tube formation assays were performed. PROX-1 expression in human HCC cells was explored by western blotting. RESULTS: PROX-1 overexpression enhanced tumor cell proliferation and inhibited apoptosis and cell cycle arrest by modulating the activities of caspase-3, PARP, and cyclin-dependent kinase inhibitors, including p21, p27, and p57 in HCC cells. After PROX-1 overexpression, the number of migrating and invading HCC cells significantly increased, and the expression levels of N-cadherin and Snail increased in HCC cells. PROX-1 overexpression enhanced angiogenesis through increased VEGF-A and VEGF-C expression and decreased angiostatin expression. PROX-1 overexpression also increased the phosphorylation of glycogen synthase kinase-3ß (GSK-3ß) and forkhead box O1 (FOXO1) in HCC cells. After PROX-1 knockdown, their phosphorylation was reversed. CONCLUSION: PROX-1 overexpression is associated with the invasive and oncogenic phenotypes of human HCC cells via GSK-3ß and FOXO1 phosphorylation.

Immunological subtyping of salivary gland cancer identifies histological origin-specific tumor immune microenvironment.

Gene expression analysis enhances proper cancer subtyping, a better understanding of the molecular characteristics of cancer, and strategies for precision medicine. However, salivary gland cancer (SGC) subtyping remains largely unexplored because of its rarity and diverse histopathological and immunological characteristics. This study aimed to determine whether the histological origin and immunological characteristics of SGC subtypes are intrinsic tumor immunity factors. We performed immune profiling of 94 RNA-seq of SGC tissues and found that the SGCs that originated from the excretory duct (ED), such as the salivary duct and mucoepidermoid carcinomas, exhibit higher immunity than those from the intercalated duct (ID), such as the adenoid cystic and myoepithelial carcinomas, based on the computationally predicted immune score (p < 0.001), immune cell enrichment in the tumor immune microenvironment (TIME) (p < 0.001), T-cell receptor diversity (p < 0.001), and expression of signal I (major histocompatibility complex, MHC, p < 0.001) and signal II (co-stimulatory, p < 0.001 and co-inhibitory, p < 0.001) genes. Further analysis revealed that tolerogenic dendritic cell-induced dysfunctional T-cell populations and T-cell exclusion in the TIME are the major immune evasive mechanisms of the ED-and ID-derived SGCs, respectively.

Impact of Local Structure in Supported CaO Catalysts for Soft-Oxidant-Assisted Methane Coupling Assessed through Ca K-Edge X-ray Absorption Spectroscopy.

Soft-oxidant-assisted methane coupling has emerged as a promising pathway to upgrade methane from natural gas sources to high-value commodity chemicals, such as ethylene, at selectivities higher than those associated with oxidative (O2) methane coupling (OCM). To date, few studies have reported investigations into the electronic structure and the microscopic physical structure of catalytic active sites present in the binary metal oxide catalyst systems that are known to be effective for this reaction. Correlating the catalyst activity to specific active site structures and electronic properties is an essential aspect of catalyst design. Here, we used X-ray absorption spectroscopy at the Ca K-edge to ascertain the most probable local environment of Ca in the ZnO-supported Ca oxide catalysts. These catalysts are shown here to be active for N2O-assisted methane coupling (N2O-OCM) and have previously been reported to be active for CO2-assisted methane coupling (CO2-OCM). X-ray absorption near edge structure features at multiple Ca loadings are interpreted through simulated spectra derived from ab initio full multiple scattering calculations. These simulations included consideration of CaO structures organized in multiple spatial arrangements-linear, planar, and cubic-with separate analyses of Ca atoms in the surfaces and bulk of the three-dimensional structures. The morphology of the oxide clusters was found to influence the various regions of the X-ray absorption spectrum differently. Experiment and theory show that for low-Ca-loading catalysts (≤1 mol %), which contain sites particularly active for methane coupling, Ca primarily exists in an oxidized state that is consistent with the coordination environment of Ca ions in one- and two-dimensional clusters. In addition to their unique nanoscale structures, the spectra also indicate that these clusters have varying degrees of undercoordinated surface Ca atoms that could further influence their catalytic activities. The local Ca structure was correlated to methane coupling activity from N2O-OCM and previously reported CO2-OCM reactor studies. This study provides a unique perspective on the relationship between the catalyst physical and electronic structure and active sites for soft-oxidant-assisted methane coupling, which can be used to inform future catalyst development.

Cation Incorporation into Copper Oxide Lattice at Highly Oxidizing Potentials.

Electrolyte cations can have significant effects on the kinetics and selectivity of electrocatalytic reactions. We show an atypical mechanism through which electrolyte cations can impact electrocatalyst performance─direct incorporation of the cation into the oxide electrocatalyst lattice. We investigate the transformations of copper electrodes in alkaline electrochemistry through operando X-ray absorption spectroscopy in KOH and Ba(OH)2 electrolytes. In KOH electrolytes, both the near-edge structure and extended fine-structure agree with previous studies; however, the X-ray absorption spectra vary greatly in Ba(OH)2 electrolytes. Through a combination of electronic structure modeling, near-edge simulation, and postreaction characterization, we propose that Ba2+ cations are directly incorporated into the lattice and form an ordered BaCuO2 phase at potentials more oxidizing than 200 mV vs the normal hydrogen electrode (NHE). BaCuO2 formation is followed by further oxidation to a bulk Cu3+-like BaxCuyOz phase at 900 mV vs NHE. Additionally, during reduction in Ba(OH)2 electrolyte, we find both Cu-O bonds and Cu-Ba scattering persist at potentials as low as -400 mV vs NHE. To our knowledge, this is the first evidence for direct oxidative incorporation of an electrolyte cation into the bulk lattice to form a mixed oxide electrode. The oxidative incorporation of electrolyte cations to form mixed oxides could open a new route for the in situ formation of active and selective oxidation electrocatalysts.

Aqueous Structure of Lanthanide-EDTA Coordination Complexes Determined by a Combined DFT/EXAFS Approach.

Sustainable production of rare earth elements (REEs) is critical for technologies needed for climate change mitigation, including wind turbines and electric vehicles. However, separation technologies currently used in REE production have large environmental footprints, necessitating more sustainable strategies. Aqueous, affinity-based separations are examples of such strategies. To make these technologies feasible, it is imperative to connect aqueous ligand structure to ligand selectivity for individual REEs. As a step toward this goal, we analyzed the extended X-ray absorption fine structure (EXAFS) of four lanthanides (La, Ce, Pr, and Nd) complexed by a common REE chelator, ethylenediaminetetraacetic acid (EDTA) to determine the aqueous-phase structure. Reference structures from density functional theory (DFT) were used to help fit the EXAFS spectra. We found that all four Ln-EDTA coordination complexes formed 9-coordinate structures with 6 coordinating atoms from EDTA (4 carboxyl oxygen atoms and 2 nitrogen atoms) and 3 oxygen atoms from water molecules. All EXAFS fits were of high quality (R-factor < 0.02) and showed decreasing average first-shell coordination distance across the series (2.62-2.57 Å from La-Nd), in agreement with DFT (2.65-2.56 Å from La-Nd). The insights determined herein will be useful in the development of ligands for sustainable rare earth elements (REE) separation technologies.

Expression of Apurinic/Apyrimidinic Endonuclease 1 in Colorectal Cancer and its Relation to Tumor Progression and Prognosis.

BACKGROUND/AIM: Over-expression of apurinic/apyrimidinic endonuclease 1 (APE1) has been demonstrated to be associated with cancer progression, chemo- and radioresistance in various cancers. This study examined the expression of APE1 and its relation to tumor progression and prognosis in patients with colorectal cancer (CRC). MATERIALS AND METHODS: We investigated 193 patients with CRC who received curative surgery for whom formalin-fixed and paraffin-embedded blocks were available, and long-term tumor-specific survival rate analysis was possible. The expression of APE1 was investigated by reverse transcription-polymerase chain reaction, western blotting, and immunohistochemistry in CRC and lymph node tissues. The apoptosis, proliferation, and angiogenesis of CRC cells were determined using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay, and immunohistochemical staining for Ki-67 and CD34 antibodies. RESULTS: APE1 was over-expressed in CRC and metastatic lymph node tissues compared with normal colorectal mucosa and non-metastatic lymph node tissues. Over-expression of APE1 was significantly associated with advanced stage, lymphovascular invasion, perineural invasion, deeper tumor invasion, lymph node metastasis, distant metastasis, and poor survival. Multivariate analysis demonstrated that APE1, perineural invasion, and lymph node metastasis were the independent prognostic factors associated with overall survival. The mean Ki-67 labeling index value of APE1-positive tumors was significantly higher than that of APE1-negative tumors. However, there was no significant association between APE1 expression and the apoptotic index or microvessel density. CONCLUSION: Over-expression of APE1 is significantly associated with tumor progression and poor survival in patients with CRC. Therefore, APE1 may be a novel biomarker and present a potential prognostic factor for CRC.

Observations of Ethylene-for-CO Ligand Exchanges on a Zeolite-Supported Single-Site Rh Catalyst by X-ray Absorption Spectroscopy.

Quick-scanning X-ray absorption fine structure (QXAFS) measurements were used to characterize the exchanges of ethylene and CO ligands in a zeolite HY-supported single-site Rh complex at a sampling rate of 1.0 Hz. The two ligands were reversibly exchanged on the rhodium, with quantitative results determined for the C2H4-for-CO exchange that are consistent with a first-order process. The apparent rate constant for the exchange decreased with increasing temperature. Fourier-transform infrared spectra characterizing the C2H4 sorbed in the zeolite showed that the amount decreased with increasing temperature, consistent with the decrease in the exchange rate with increasing temperature. The results, illustrating the dynamics of ligand exchanges on a single-site supported metal catalyst, demonstrate the broad emerging applicability of the QXAFS technique for characterizing the dynamics of reactive intermediates on catalysts.

Memory-dictated dynamics of single-atom Pt on CeO2 for CO oxidation.

Single atoms of platinum group metals on CeO2 represent a potential approach to lower precious metal requirements for automobile exhaust treatment catalysts. Here we show the dynamic evolution of two types of single-atom Pt (Pt1) on CeO2, i.e., adsorbed Pt1 in Pt/CeO2 and square planar Pt1 in PtATCeO2, fabricated at 500 °C and by atom-trapping method at 800 °C, respectively. Adsorbed Pt1 in Pt/CeO2 is mobile with the in situ formation of few-atom Pt clusters during CO oxidation, contributing to high reactivity with near-zero reaction order in CO. In contrast, square planar Pt1 in PtATCeO2 is strongly anchored to the support during CO oxidation leading to relatively low reactivity with a positive reaction order in CO. Reduction of both Pt/CeO2 and PtATCeO2 in CO transforms Pt1 to Pt nanoparticles. However, both catalysts retain the memory of their initial Pt1 state after reoxidative treatments, which illustrates the importance of the initial single-atom structure in practical applications.

Dynamic Evolution of Palladium Single Atoms on Anatase Titania Support Determines the Reverse Water-Gas Shift Activity.

Research interest in single-atom catalysts (SACs) has been continuously increasing. However, the lack of understanding of the dynamic behaviors of SACs during applications hinders catalyst development and mechanistic understanding. Herein, we report on the evolution of active sites over Pd/TiO2-anatase SAC (Pd1/TiO2) in the reverse water-gas shift (rWGS) reaction. Combining kinetics, in situ characterization, and theory, we show that at T ≥ 350 °C, the reduction of TiO2 by H2 alters the coordination environment of Pd, creating Pd sites with partially cleaved Pd-O interfacial bonds and a unique electronic structure that exhibit high intrinsic rWGS activity through the carboxyl pathway. The activation by H2 is accompanied by the partial sintering of single Pd atoms (Pd1) into disordered, flat, ∼1 nm diameter clusters (Pdn). The highly active Pd sites in the new coordination environment under H2 are eliminated by oxidation, which, when performed at a high temperature, also redisperses Pdn and facilitates the reduction of TiO2. In contrast, Pd1 sinters into crystalline, ∼5 nm particles (PdNP) during CO treatment, deactivating Pd1/TiO2. During the rWGS reaction, the two Pd evolution pathways coexist. The activation by H2 dominates, leading to the increasing rate with time-on-stream, and steady-state Pd active sites similar to the ones formed under H2. This work demonstrates how the coordination environment and nuclearity of metal sites on a SAC evolve during catalysis and pretreatments and how their activity is modulated by these behaviors. These insights on SAC dynamics and the structure-function relationship are valuable to mechanistic understanding and catalyst design.

Variability of oral/taste sensitivity to fat: An investigation of attribution from detection threshold methods with repeated measurements.

Accumulating psychophysical evidence suggests substantial individual variability in oral/taste sensitivity to non-esterified, long-chain fatty acids (NEFA), which is commonly referred to as fat taste or oleogustus. Recent studies have sought to determine its associations with human factors such as body mass index (BMI) and food preferences, as it has been claimed that excessive fat consumption is related to several health conditions, including obesity. Yet, the findings are controversial. On the other hand, it has been noted that considerable variability also occurs based on the methodology used to measure the fatty acid taste. Specifically, learning effects have been observed over repeated measurements of the detection threshold of NEFA, yet there has been no methodology available to take into account these learning effects. Accordingly, in the present study, a novel methodology using a descending-block dual reminder A-Not A (DR A-Not A) method with a warm-up has been proposed to measure the NEFA detection threshold based on the signal detection theory and considering NEFA taste learning effects over repeated sessions. Homogeneous subjects (young adult Korean females within the normal BMI range, non-vegetarians) were randomized to either the novel descending-block DR A-Not A method or ascending triangle method that is commonly used for fat perception studies. Pure oleic acid emulsions were used as fat taste stimuli to be discriminated from pure mineral water. Each subject completed 14 repeated visits. For the ascending triangle method, 14 thresholds were determined using a stopping rule, while for the novel method, 7 thresholds were determined each per two consecutive days, using a criterion of a lower limit of 50% confidence interval of d' = 0.5, considering the practical aspects of taste studies in food sensory science. Based on the group median results of the last two visits, the variability of the detection thresholds was reduced using the novel descending-block DR A-Not A method due to better learning effects over repeated sessions. This shows the potential of the descending-block DR A-Not A threshold method for further studies on oral/taste sensitivity to fat.

The role of the prefrontal cortex in semantic control for selecting weakly associated meanings in creative idea generation.

Although semantic control is known to play a critical role in selecting weakly associated representations for creative idea generation, direct evidence for this is still lacking. The current study aimed to reveal the role of brain regions, including the inferior frontal gyrus (IFG), medial frontal gyrus (MFG), and inferior parietal lobule (IPL), previously reported to be associated with creative idea generation. For this purpose, a functional MRI experiment with a newly developed category judgment task was conducted, which required participants to judge whether two words belonged to the same category. Importantly, weakly associated meanings were manipulated by the task condition, which required selecting an unused meaning of the homonym in a preceding semantic context. The results showed that the selection of a weakly associated meaning for a homonym was associated with an increased activation of the IFG and MFG and a decreased activation of the IPL. These results suggest that IFG and MFG contribute to semantic control processes recruited for the selection of weakly associated meanings and self-guided retrieval, whereas IPL appears to be unrelated to the control demand for creative idea generation.

Structure and Site Evolution of Framework Ni Species in MIL-127 MOFs for Propylene Oligomerization Catalysis.

A mixed-valence oxotrimer metal-organic framework (MOF), Ni-MIL-127, with a fully coordinated nickel atom and two iron atoms in the inorganic node, generates a missing linker defect upon thermal treatment in helium (>473 K) to engender an open coordination site on nickel which catalyzes propylene oligomerization devoid of any cocatalysts or initiators. This catalyst is stable for ∼20 h on stream at 500 kPa and 473 K, unprecedented for this chemistry. The number of missing linkers on synthesized and activated Ni-MIL-127 MOFs is quantified using temperature-programmed oxidation, 1H nuclear magnetic resonance spectroscopy, and X-ray absorption spectroscopy to be ∼0.7 missing linkers per nickel; thus, a majority of Ni species in the MOF framework catalyze propylene oligomerization. In situ NO titrations under reaction conditions enumerate ∼62% of the nickel atoms as catalytically relevant to validate the defect density upon thermal treatment. Propylene oligomerization rates on Ni-MIL-127 measured at steady state have activation energies of 55-67 kJ mol-1 from 448 to 493 K and are first-order in propylene pressures from 5 to 550 kPa. Density functional theory calculations on cluster models of Ni-MIL-127 are employed to validate the plausibility of the missing linker defect and the Cossee-Arlman mechanism for propylene oligomerization through comparisons between apparent activation energies from steady-state kinetics and computation. This study illustrates how MOF precatalysts engender defective Ni species which exhibit reactivity and stability characteristics that are distinct and can be engineered to improve catalytic activity for olefin oligomerization.

Engulfment and Cell Motility 1 (ELMO1) Regulates Tumor Cell Behavior and Predicts Prognosis in Colorectal Cancer.

BACKGROUND/AIM: Engulfment and cell motility 1 (ELMO1) plays a crucial role in the process of migration, chemotaxis, and metastasis of tumor cells. ELMO1 has been implicated in the pathogenesis of various cancers. However, the distinct function of ELMO1 in colorectal cancer (CRC) is unclear. We determined whether ELMO1 affects the oncogenic behavior of CRC cells and investigated its prognostic value in CRC patients. MATERIALS AND METHODS: We investigated the impact of ELMO1 on tumor cell behavior using small interference RNA (siRNA) in CRC cell lines, including SW480 and DLD1. The expression of ELMO1 was investigated by reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA) in cancer tissues and sera obtained from CRC patients. RESULTS: ELMO1 knockdown suppressed tumor cell proliferation in SW480 and DLD1 cells. ELMO1 knockdown-induced apoptosis through up-regulation of caspase-3, -7, and PARP activities and down-regulation of the anti-apoptotic Mcl-1 protein. ELMO1 knockdown-induced cell-cycle arrest by decreasing cyclin D1, cyclin-dependent kinase 2, 4 and 6, and the 25C cell division cycle (CDC25C). ELMO1 knockdown suppressed tumor cell invasion and migration. The expression of E-cadherin was increased, while that of Vimentin and Claudin 1 decreased following ELMO1 knockdown. The phosphorylation levels of PDK1, Akt, and GSK-3ß and were down-regulated after ELMO1 knockdown. The expression of ELMO1 was found up-regulated in cancer tissues and sera taken from CRC patients. ELMO1 expression was significantly associated with tumor stage, lymph node metastasis, distant metastases, and poor survival. CONCLUSION: ELMO1 mediates tumor progression by increasing tumor cell motility and inhibiting apoptosis in human CRC.

Clinical outcomes of palliative self-expandable metal stent placement in right- and left-sided malignant colon obstruction: A Honam Association for the Study of Intestinal Disease (HASID) multicenter study.

Self-expandable metal stent (SEMS) placement is commonly used for palliation of left-sided malignant colorectal obstruction (MCO). However, right-sided MCO is usually treated surgically. Recent studies that compared palliative SEMS insertion and emergency surgery in right-sided MCOs have reported conflicting results. This study aimed to compare the effectiveness of palliative SEMS placement in left-sided MCOs and right-sided MCOs and to investigate the predictive factors for clinical success and risk factors for complications. Data from 469 patients who underwent palliative SEMS placement for MCO at 6 hospitals in the Honam province of South Korea between 2009 and 2018 were reviewed. Among them, 69 patients with right-sided MCO and 400 patients with left-sided MCO who underwent SEMS placement for palliative purposes were enrolled. Clinical success, overall survival, complications, and predictive factors for clinical success and risk factors for complications were included as the main outcome measures. The clinical success rates were 97.1% (65/67) in right-sided MCO patients and 88.2% (353/400) in left-sided MCO patients. Complications including stent migration, tumor ingrowth, outgrowth, perforation, bacteremia/fever, and bleeding occurred in 10.1% (7/69) of right-sided MCO patients and 19.9% (79/400) of left-sided MCO patients. The mean overall survival of right-sided MCO was 28.02 months and 18.23 months for left-sided MCO. In multivariate logistic regression analysis, T3 stage tumors and the use of uncovered stents were significant factors for the clinical success of SEMS. The use of covered stents and performance status score of 0 to 2 were independent significant risk factors for complications. Palliative SEMS placement in right-sided MCO showed better clinical success rates than left-sided MCO. The use of uncovered stents is recommended for higher clinical success rates and lower complication rates.

HLA-I-restricted CD8+ T cell immunity may accelerate tumorigenesis in conjunction with VHL inactivation.

CD8+ T cells recognize and kill tumor cells with HLA-I tumor antigens in early tumorigenesis, the efficiency of which differs according to antigen-recognition coverage, as shown in earlier tumor onset in HLA-I homozygosity. However, the universality of these associations remains unknown. Here, we assessed the tumor type and driver mutation specificity in the association between tumor onset age and HLA-I zygosity. Statistical analyses identified an unexpected negative relationship in tumors with VHL biallelic loss, wherein HLA-I heterozygosity was associated with earlier tumor onset, while all others showed either no or a positive association. Testing on an independent dataset reproduced the VHL-dependent acceleration of tumor onset in the HLA-I heterozygous group, confirming the association. Further speculation proposed VEGF-A-mediated T cell exhaustion under VHL inactivation as a potential mechanism. Our findings suggest that CD8+ T cell immunity in early tumor suppression can be conditional to the genetic status of tumors and may even lead to adverse consequences.