ASF1B acted as a prognostic biomarker for stomach adenocarcinoma.

Stomach adenocarcinoma (STAD) has a high mortality rate due to the lack of highly sensitive biomarkers. Therefore, the search for potential tumor markers is of great value. ASF1B is a prognostic marker for a variety of tumors, while the prognostic value and immune microenvironment of ASF1B in STAD remain unclear, and to be determined. Kaplan-Meier analysis was performed to analyze the prognostic role of ASF1B in STAD. Functional enrichment of ASF1B was explored with GO and KEGG pathway analysis. We also explored the correlation between ASF1B expression and immune infiltration in STAD. ASF1B was significantly upregulated in STAD tissues and high expression of ASF1B indicated a poor overall survival, progression-free survival, and first progression rate in STAD. The functional enrichment analysis of ASF1B and related genes showed high enrichment in the cell cycle and DNA repair, and the ASF1B high expression group was also mainly enriched in pathways such as the cell cycle. Analysis of tumor immune infiltration showed that ASF1B expression was significantly associated with the majority of immune cell infiltration in STAD. Moreover, STAD patients with high ASF1B expression had a higher tumor mutation burden score, microsatellite instability score, PD-1 immunophenoscore, and immune checkpoint expression. Our results suggest that ASF1B was an independent prognostic factor for STAD as well as a potential target for immunotherapy.

Mendelian Randomization Analyses of Chronic Immune-Mediated Diseases, Circulating Inflammatory Biomarkers, and Cytokines in Relation to Liver Cancer.

Liver cancer is closely linked to chronic inflammation. While observational studies have reported positive associations between extrahepatic immune-mediated diseases and systemic inflammatory biomarkers and liver cancer, the genetic association between these inflammatory traits and liver cancer remains elusive and merits further investigation. We conducted a two-sample Mendelian randomization (MR) analysis, using inflammatory traits as exposures and liver cancer as the outcome. The genetic summary data of both exposures and outcome were retrieved from previous genome-wide association studies (GWAS). Four MR methods, including inverse-variance-weighted (IVW), MR-Egger regression, weighted-median, and weighted-mode methods, were employed to examine the genetic association between inflammatory traits and liver cancer. Nine extrahepatic immune-mediated diseases, seven circulating inflammatory biomarkers, and 187 inflammatory cytokines were analyzed in this study. The IVW method suggested that none of the nine immune-mediated diseases were associated with the risk of liver cancer, with odds ratios of 1.08 (95% CI 0.87-1.35) for asthma, 0.98 (95% CI 0.91-1.06) for rheumatoid arthritis, 1.01 (95% CI 0.96-1.07) for type 1 diabetes, 1.01 (95% CI 0.98-1.03) for psoriasis, 0.98 (95% CI 0.89-1.08) for Crohn's disease, 1.02 (95% CI 0.91-1.13) for ulcerative colitis, 0.91 (95% CI 0.74-1.11) for celiac disease, 0.93 (95% CI 0.84-1.05) for multiple sclerosis, and 1.05 (95% CI 0.97-1.13) for systemic lupus erythematosus. Similarly, no significant association was found between circulating inflammatory biomarkers and cytokines and liver cancer after correcting for multiple testing. The findings were consistent across all four MR methods used in this study. Our findings do not support a genetic association between extrahepatic inflammatory traits and liver cancer. However, larger-scale GWAS summary data and more genetic instruments are needed to confirm these findings.

LncRNA model predicts liver cancer drug resistance and validate in vitro experiments.

Introduction: Hepatocellular carcinoma (HCC) patients may benefit from chemotherapy, but drug resistance is an important obstacle to favorable prognoses. Overcoming drug resistance is an urgent problem to be solved. Methods: Differential expression analysis was used to identify long non-coding RNAs (LncRNAs) that differed in chemotherapy-sensitive and chemotherapy-resistant patients. Machine learning algorithms including random forest (RF), lasso regression (LR), and support vector machines (SVMs) were used to identify important chemotherapy-related LncRNAs. A back propagation (BP) network was then used to validate the predictive capacity of important LncRNAs. The molecular functions of hub LncRNAs were investigated via qRT-PCR and cell proliferation assay. Molecular-docking technique was used to explore candidate drug of targets of hub LncRNA in the model. Results: A total of 125 differentially expressed LncRNAs between sensitive and resistant patients. Seventeen important LncRNAs were identified via RF, and seven factors were identified via LR. With respect to SVM, the top 15 LncRNAs of AvgRank were selected. Five merge chemotherapy-related LncRNAs were used to predict chemotherapy resistance with high accuracy. CAHM was a hub LncRNA of model and expression high in sorafenib resistance cell lines. In addition, the results of CCK8 showed that the sensitivity of HepG2-sorafenib cells to sorafenib was significantly lower than that of HepG2; and the sensitivity of HepG2-sorafenib cells transfected with sh-CAHM was significantly higher than that of Sorafenib. In the non-transfection group, the results of clone formation experiments showed that the number of clones formed by HepG2-sorafenib cells treated with sorafenib was significantly more than that of HepG2; after HepG2-sorafenib cells were transfected with sh-CAHM, the number of clones formed by Sorafenib treatment was significantly higher than that of HepG2 cells. The number was significantly less than that of HepG2-s + sh-NC group. Molecular Docking results indicate that Moschus was candidate drug for target protein of CAHM. Conclusion: Five chemotherapy-related LncRNAs could predict drug resistance in HCC with high accuracy, and the hub LncRNA CAHM has potential as a new biomarker for HCC chemotherapy resistance.

Structurally Precise Two-Transition-Metal Water Oxidation Catalysts: Quantifying Adjacent 3d Metals by Synchrotron X-Radiation Anomalous Dispersion Scattering.

Mixed 3d metal oxides are some of the most promising water oxidation catalysts (WOCs), but it is very difficult to know the locations and percent occupancies of different 3d metals in these heterogeneous catalysts. Without such information, it is hard to quantify catalysis, stability, and other properties of the WOC as a function of the catalyst active site structure. This study combines the site selective synthesis of a homogeneous WOC with two adjacent 3d metals, [Co2Ni2(PW9O34)2]10- (Co2Ni2P2) as a tractable molecular model for CoNi oxide, with the use of multiwavelength synchrotron X-radiation anomalous dispersion scattering (synchrotron XRAS) that quantifies both the location and percent occupancy of Co (∼97% outer-central-belt positions only) and Ni (∼97% inner-central-belt positions only) in Co2Ni2P2. This mixed-3d-metal complex catalyzes water oxidation an order of magnitude faster than its isostructural analogue, [Co4(PW9O34)2]10- (Co4P2). Four independent and complementary lines of evidence confirm that Co2Ni2P2 and Co4P2 are the principal WOCs and that Co2+(aq) is not. Density functional theory (DFT) studies revealed that Co4P2 and Co2Ni2P2 have similar frontier orbitals, while stopped-flow kinetic studies and DFT calculations indicate that water oxidation by both complexes follows analogous multistep mechanisms, including likely Co-OOH formation, with the energetics of most steps being lower for Co2Ni2P2 than for Co4P2. Synchrotron XRAS should be generally applicable to active-site-structure-reactivity studies of multi-metal heterogeneous and homogeneous catalysts.

Risk factors for concomitant infectious pancreatic necrosis in patients with severe acute pancreatitis: A systematic review and meta-analysis.

OBJECTIVE: Acute pancreatitis (AP) is a self-limiting disease. However, 20-30% of patients will develop into severe AP (SAP), and infectious pancreatic necrosis in the late course of SAP is the leading cause of death for such patients. This review aims to provide a comprehensive and systematic report of the currently published risk factors for complicated infectious pancreatic necrosis in patients with severe acute pancreatitis by meta-analysis of published retrospective case-control studies. METHODS: Five electronic database systems were selected to search for articles on risk factors of infectious pancreatic necrosis in patients with severe acute pancreatitis. According to the heterogeneity among studies, the standardized mean difference (SMD), odds ratio and 95% confidence interval (95%CI) were calculated by applying a random-effects model or fixed-effects model, respectively. RESULTS: As of 2nd Jun, 2021, a total of 1408 articles were searched, but only 21 articles were finally included in this meta-analysis. The results found that patients with severe acute pancreatitis complicated by infected pancreatic necrosis had higher APACHE II scores and higher levels of lipase (LPS), C-reactive protein (CRP) and procalcitonin (PCT) compared to patients with severe acute pancreatitis alone. The differences were statistically significant (APACHE II: SMD = 0.86, 95%CI: 0.55, 1.18; LPS: SMD = 1.52, 95%CI: 1.13, 1.92; CRP: SMD = 1.42, 95%CI: 1.05, 1.79; PCT: SMD = 1.82, 95%CI: 1.36, 2.28). CONCLUSIONS: Compared with patients with severe acute pancreatitis alone, high levels of LPS, CRP, PCT and high APACHE II score were risk factors for infectious pancreatic necrosis in patients with severe acute pancreatitis.

Sorafenib prevents the proliferation and induces the apoptosis of liver cancer cells by regulating autophagy and hypoxia-inducible factor-1.

Sorafenib has been approved as a systemic drug for advanced liver cancer; however, the underlying mechanisms remain unclear. The present study aimed to investigate the effects of sorafenib on the proliferation, autophagy and apoptosis of HepG2 cells under hypoxia. Briefly, reverse transcription-quantitative PCR and western blotting was performed to quantify HIF-1, LC3II/I, mTOR and p70s6K expression levels. Cell proliferation was determined using the Cell Counting Kit-8 assay and the cell apoptosis rate was evaluated using flow cytometry. The results demonstrated that autophagy and apoptosis were induced by hypoxia, and that sorafenib further enhanced hypoxia-induced autophagy and apoptosis in HepG2 cells in a dose-dependent manner. Furthermore, the mechanism of sorafenib-mediated autophagy in liver cancer cell were investigated by using chloroquine (CQ). The results showed that CQ significantly inhibited autophagy by decreasing LC3II/LC3I ratio in HepG2 cells treated with sorafenib and/or hypoxia. By contrast, sorafenib could increase the expression of hypoxia-inducible factor-1 (HIF-1) and of the autophagy marker (LC3II/I) and decrease the expression of mammalian target of rapamycin and p70 ribosomal S6 kinase in HepG2 cells under normoxia and hypoxia conditions, suggesting that sorafenib could induce hypoxia and autophagy in liver cancer cells. In addition, sorafenib was demonstrated to prevent proliferation and induce apoptosis of HepG2 cells under normoxia and hypoxia. Sorafenib could also prevent the malignant behavior of HepG2 by inducing hypoxia and autophagy. In summary, the findings from the present study suggested that sorafenib may inhibit liver cancer progression by activating autophagy and HIF-1 signaling pathway.

Ion-pairing in polyoxometalate chemistry: impact of fully hydrated alkali metal cations on properties of the keggin [PW12O40]3- anion.

The counterions of polyoxometalates (POMs) impact properties and applications of this growing class of inorganic clusters. Here, we used density functional theory (DFT) to elucidate the impact of fully hydrated alkali metal cations on the geometry, electronic structure, and chemical properties of the polyoxotungstate anion [PW12O40]3-. The calculations show that the HOMO of the free anion [PW12O40]3- is a linear combination of the 2p AOs of the bridging oxygens, and the first few LUMOs are the 5d orbitals of the tungsten atoms. The S0→ S1 electron excitation, near 3 eV, is associated with the O(2p) → W(5d) transition. Anion/cation complexation leads to formation of [PW12O40]3-[M+(H2O)16]3 ion-pair complexes, where with the increase of atomic number of M, the M+(H2O)16 cluster releases several water molecules and interacts strongly with the polyoxometalate anion. For M = Li, Na and K, [PW12O40]3-[M+(H2O)16]3 is characterized as a "hydrated" ion-pair complex. However, for M = Rb and Cs, it is a "contact" ion-pair complex, where the strong anion-cation interaction makes it a better electron acceptor than the "hydrated" ion-pair complexes. Remarkably, the electronic excitations in the visible part of the absorption spectrum of these complexes are predominantly solvent-to-POM charge transfer transitions (i.e. intermolecular CT). The ratio of the number of intermolecular charge transfer transitions to the number of O(2p)-to-W(5d) valence (i.e. intramolecular) transitions increases with the increasing atomic number of the alkali metals.

Calpain Small Subunit 1 Protein in the Prognosis of Cancer Survivors and Its Clinicopathological Correlation.

Background/Aims. Calpain small subunit 1 (Capn4) is implicated in tumorigenesis and plays a key role in multiple tumors. This study aimed to fully illustrate the prognostic value of Capn4 protein in cancer patients. METHODS: A systematic search was conducted against several online databases. Hazard ratios (HRs) or odds ratio (ORs) were used to investigate the relationship between Capn4 protein expression and prognosis as well as clinical parameters in cancer survivors. RESULTS: Eleven studies involving 1775 patients were identified. Overall, the results showed that Capn4 protein was associated with poor prognosis of overall survival (OS) (HR=1.74; 95% CI:1.47-2.01; p<0.001) and event-free survival (EFS) (HR=1.73; 95% CI:1.39-2.07; p<0.001) and event-free survival (EFS) (HR=1.73; 95% CI:1.39-2.07; p<0.001) and event-free survival (EFS) (HR=1.73; 95% CI:1.39-2.07; p<0.001) and event-free survival (EFS) (HR=1.73; 95% CI:1.39-2.07; p<0.001) and event-free survival (EFS) (HR=1.73; 95% CI:1.39-2.07; p<0.001) and event-free survival (EFS) (HR=1.73; 95% CI:1.39-2.07; p<0.001) and event-free survival (EFS) (HR=1.73; 95% CI:1.39-2.07; p<0.001) and event-free survival (EFS) (HR=1.73; 95% CI:1.39-2.07; p<0.001) and event-free survival (EFS) (HR=1.73; 95% CI:1.39-2.07. CONCLUSIONS: Expression of Capn4 protein is associated with cancer survival and clinicopathologic characteristics in patients.

Multi-Tasking POM Systems.

Polyoxometalate (POM)-based materials of current interest are summarized, and specific types of POM-containing systems are described in which material facilitates multiple complex interactions or catalytic processes. We specifically highlight POM-containing multi-hydrogen-bonding polymers that form gels upon exposure to select organic liquids and simultaneously catalyze hydrolytic or oxidative decontamination, as well as water oxidation catalysts (WOCs) that can be interfaced with light-absorbing photoelectrode materials for photoelectrocatalytic water splitting.

Polyoxometalate-based gelating networks for entrapment and catalytic decontamination.

We report the synthesis and characterization of a new class of organic/inorganic hybrid polymers composed of covalently-bound 1,3,5-benzenetricarboxamide linkers and anionic polyoxovanadate clusters with varying counter-cations. These materials form gels within seconds upon contact with polar aprotic organic liquids and catalyze the degradation of odorants and toxic molecules under mild conditions including aerobic oxidation of thiols, hydrogen peroxide-catalyzed oxidation of sulfides, and hydrolysis of organophosphate chemical warfare agent analogues.

Stabilization of Polyoxometalate Water Oxidation Catalysts on Hematite by Atomic Layer Deposition.

Fast and earth-abundant-element polyoxometalates (POMs) have been heavily studied recently as water oxidation catalysts (WOCs) in homogeneous solution. However, POM WOCs can be quite unstable when supported on electrode or photoelectrode surfaces under applied potential. This article reports for the first time that a nanoscale oxide coating (Al2O3) applied by the atomic layer deposition (ALD) aids immobilization and greatly stabilizes this now large family of molecular WOCs when on electrode surfaces. In this study, [{RuIV4(OH)2(H2O)4}(γ-SiW10O34)2]10- (Ru4Si2) is supported on hematite photoelectrodes and then protected by ALD Al2O3; this ternary system was characterized before and after photoelectrocatalytic water oxidation by Fourier transform infrared, X-ray photoelectron spectroscopy, energy-dispersive X-ray, and voltammetry. All these studies indicate that Ru4Si2 remains intact with Al2O3 ALD protection, but not without. The thickness of the Al2O3 layer significantly affects the catalytic performance of the system: a 4 nm thick Al2O3 layer provides optimal performance with nearly 100% faradaic efficiency for oxygen generation under visible-light illumination. Al2O3 layers thicker than 6.5 nm appear to completely bury the Ru4Si2 catalyst, removing all of the catalytic activity, whereas thinner layers are insufficient to maintain a long-term attachment of the catalytic POM.

Efficient light-driven carbon-free cobalt-based molecular catalyst for water oxidation.

The abundant-metal-based polyoxometalate complex [Co(4)(H(2)O)(2)(PW(9)O(34))(2)](10-) is a hydrolytically and oxidatively stable, homogeneous, and efficient molecular catalyst for the visible-light-driven catalytic oxidation of water. Using a sacrificial electron acceptor and photosensitizer, it exhibits a high (30%) photon-to-O(2) yield and a large turnover number (>220, limited solely by depletion of the sacrificial electron acceptor) at pH 8. The photocatalytic performance of this catalyst is superior to that of the previously reported precious-metal-based polyoxometalate water oxidation catalyst [{Ru(4)O(4)(OH)(2)(H(2)O)(4)}(γ-SiW(10)O(36))(2)](10-).

Insights into photoinduced electron transfer between [Ru(mptpy)2]4+ (mptpy = 4'(4-methylpyridinio)-2,2':6',2''-terpyridine) and [S2O8]2-: computational and experimental studies.

The mechanism and electron transfer dynamics of the reaction [Ru(II)(mptpy)(2)](4+) + hnu + [S(2)O(8)](2-) --> [Ru(III)(mptpy)(2)](5+) + SO(4)(2-) + SO(4)(-*) were studied using various computational (density functional and exciton interaction theories) and experimental (transient absorption, static and time-resolved fluorescence spectroscopy, and other) techniques. The results were compared with those recently reported for [Ru(bpy)(3)](2+) dye [ref 18]. It was found that the excitation energy of [Ru(mptpy)(2)](4+) is about 0.4-0.5 eV smaller than that of [Ru(bpy)(3)](2+), which is consistent with the measured absorption maxima of 445 and 507 nm, for [Ru(bpy)(3)](2+) and [Ru(mptpy)(2)](4+), respectively. The smaller excitation energy in [Ru(mptpy)(2)](4+) correlates with much slower electron transfer rates to persulfate compared to [Ru(bpy)(3)](2+). The quenching of the photoexcited [Ru(mptpy)(2)](4+) by [S(2)O(8)](2-) occurs via a unimolecular mechanism with formation of a weak ion-pair complex {[Ru(mptpy)(2)](4+)...([S(2)O(8)](2-))(n)}, where n = 1 and 2. The initial photon is absorbed by the [Ru(mptpy)(2)](4+) fragment forming an MLCT state, e.g., the bright singlet state S1. This S1 state undergoes a fast spin-orbit coupling induced intersystem crossing to a lower-lying triplet and rapid subsequent relaxation down to the lowest triplet T1 via internal conversion and collisions with solvent molecules. At this stage, the electron transfer from [Ru(mptpy)(2)](4+) to a loosely attached [S(2)O(8)](2-) occurs in a dark reaction via elongation of the O-O peroxo bond of the oxidant [S(2)O(8)](2-). The electron transfer lifetimes in water are calculated to be 1/kappa(1) = 199.4 ns and 1/kappa(2) = 108.4 ns, for the 1:1 and 1:2 complexes, respectively. The computed electron transfer lifetimes (1/kappa(1)) are in reasonable agreement with their experimental values of 298 and 149 ns for the 1:1 and 1:2 complexes, respectively. The effect of solvent polarity on electron transfer rates is found to be significant: the less polar acetonitrile slows the rate by an order of magnitude compared to water.

A fast soluble carbon-free molecular water oxidation catalyst based on abundant metals.

Traditional homogeneous water oxidation catalysts are plagued by instability under the reaction conditions. We report that the complex [Co4(H2O)2(PW9O34)2]10-, comprising a Co4O4 core stabilized by oxidatively resistant polytungstate ligands, is a hydrolytically and oxidatively stable homogeneous water oxidation catalyst that self-assembles in water from salts of earth-abundant elements (Co, W, and P). With [Ru(bpy)3]3+ (bpy is 2,2'-bipyridine) as the oxidant, we observe catalytic turnover frequencies for O2 production > or = 5 s(-1) at pH = 8. The rate's pH sensitivity reflects the pH dependence of the four-electron O2-H2O couple. Extensive spectroscopic, electrochemical, and inhibition studies firmly indicate that [Co4(H2O)2(PW9O34)2]10- is stable under catalytic turnover conditions: Neither hydrated cobalt ions nor cobalt hydroxide/oxide particles form in situ.

Structural, physicochemical, and reactivity properties of an all-inorganic, highly active tetraruthenium homogeneous catalyst for water oxidation.

Several key properties of the water oxidation catalyst Rb(8)K(2)[{Ru(IV)(4)O(4)(OH)(2)(H(2)O)(4)}(gamma-SiW(10)O(36))(2)] and its mechanism of water oxidation are given. The one-electron oxidized analogue [{Ru(V)Ru(IV)(3)O(6)(OH(2))(4)}(gamma-SiW(10)O(36))(2)](11-) has been prepared and thoroughly characterized. The voltammetric rest potentials, X-ray structures, elemental analysis, magnetism, and requirement of an oxidant (O(2)) indicate these two complexes contain [Ru(IV)(4)O(6)] and [Ru(V)Ru(IV)(3)O(6)] cores, respectively. Voltammetry and potentiometric titrations establish the potentials of several couples of the catalyst in aqueous solution, and a speciation diagram (versus electrochemical potential) is calculated. The potentials depend on the nature and concentration of counterions. The catalyst exhibits four reversible couples spanning only ca. 0.5 V in the H(2)O/O(2) potential region, keys to efficient water oxidation at low overpotential and consistent with DFT calculations showing very small energy differences between all adjacent frontier orbitals. The voltammetric potentials of the catalyst are evenly spaced (a Coulomb staircase), more consistent with bulk-like properties than molecular ones. Catalysis of water oxidation by [Ru(bpy)(3)](3+) has been examined in detail. There is a hyperbolic dependence of O(2) yield on catalyst concentration in accord with competing water and ligand (bpy) oxidations. O(2) yields, turnover numbers, and extensive kinetics data reveal several features and lead to a mechanism involving rapid oxidation of the catalyst in four one-electron steps followed by rate-limiting H(2)O oxidation/O(2) evolution. Six spectroscopic, scattering, and chemical experiments indicate that the catalyst is stable in solution and under catalytic turnover conditions. However, it decomposes slowly in acidic aqueous solutions (pH < 1.5).