TRIM69: a marker of metastasis and potential sensitizer to 5-Fluorouracil and PD-1 blockers in colon adenocarcinoma.

BACKGROUND: Several proteins in the tripartite-motif (TRIM) family are associated with the development of colorectal cancer (CRC), but research on the role of TRIM69 was lacking. The present study examined the correlation between TRIM69 expression and colon adenocarcinoma (COAD). METHODS: mRNA sequencing data for COAD patients was extracted from The Cancer Genome Atlas to analyze correlations between TRIM69 expression and patients' clinical features as well as survival. Potential associations with immune cells and chemosensitivity also were predicted using various algorithms in the TIMER, Limma, clusterProfiler, GeneMANIA, and Gene Set Cancer Analysis platforms. Subsequently, polymerase chain reaction analysis and immunohistochemical staining were used to detect TRIM69 expression in COAD tissue samples from real-world patients. RESULTS: TRIM69 expression was lower in COAD tissues than in normal tissues and correlated with the pathologic stage and metastasis (M category). Additionally, TRIM69 was found to be involved in several immune-related pathways, notably the NOD-like signaling pathway. These results suggest that high TRIM69 expression has the potential to enhance tumor sensitivity to 5-fluorouracil and programmed cell death protein 1 (PD-1) blockers. CONCLUSIONS: From our findings that TRIM69 expression was significantly reduced in COAD compared with non-cancer tissues and associated with pathologic stage and metastasis, we conclude that increasing TRIM69 expression and/or activity may help to improve therapeutic outcomes. Accordingly, TRIM69 represents a potentially valuable marker of metastasis and target for adjuvant therapy in COAD.

Distinctive Characteristics of Al7Li: A Superatom Counterpart of Group IVA Elements.

A new superatom of dual valence states, namely Al7Li, has been proposed to further enrich the "three-dimensional periodic table". It bears great resemblance to group IVA elements in many aspects. Chief among them is that Al7Li favors both +2 and +4 oxidation states, which makes it analogous to the heavier carbon-group elements. Al7Li is capable of forming stable ionic compounds with carbon, oxygen, and fluorine and forming covalent tetrahydride with hydrogen, just as how germanium, tin, and lead atoms combine with these elements to form stable molecules. The nearest atomic counterpart of Al7Li in group IV is probably Sn or Pb since their oxides and tetrahydrides share like characteristics.

Stability and Nonlinear Optical Response of Alkalides that Contain a Completely Encapsulated Superalkali Cluster.

Guided by density functional theory (DFT) computations, a new series of superalkali-based alkalides, namely FLi2 (+) (aza222)K(-) , OLi3 (+) (aza222)K(-) , NLi4 (+) (aza222)K(-) , and Li3 (+) (aza222)K(-) were designed with various superalkali clusters embedded into an aza222 cage-complexant. These species possess diverse isomeric structures in which the encapsulated superalkalis preserve their identities and behave as alkali metal atoms. The results show that these novel alkalides possess larger complexation energies and enhanced hyperpolarizabilities (ß0 ) compared with alkali-metal-based and previous superalkali-based clusters. Especially, a prominent structural dependence of ß0 is observed for these studied compounds. Hence, the geometric factors that affect the nonlinear optical (NLO) response of such alkalides is elucidated in detail in this work. This study not only provides novel candidates for alkalides, it also offers an effective way to enhance the NLO response and stability of alkalides.

A theoretical study on novel alkaline earth-based excess electron compounds: unique alkalides with considerable nonlinear optical responses.

On the basis of stable alkaline earth metal ammines, a series of M(NH3)6NaCl and M(NH3)6Na2 (M = Mg and Ca) excess electron compounds were theoretically constructed and studied by using the density functional theory. The electride or alkalide characteristics of these compounds are verified by their electronic structures, HOMOs, and small VIE values. It is worth noting that the M(NH3)6Na2 alkalides have novel electronic structures that contain double alkali metal anions. As expected, all the noncentrosymmetric M(NH3)6NaCl and M(NH3)6Na2 compounds possess considerable first hyperpolarizabilities (ß0) up to 123 050 au, which can be attributed to low excitation energies (ΔEs) and large oscillator strength (f0) of their crucial excited states. In addition, results reveal that the Ca(NH3)6-based species with lower ΔEs and larger transition moments (Δµ) show larger ß0 values compared with the corresponding Mg(NH3)6-based ones with similar geometries. This study may be significant in terms of designing excess electron compounds of new-type, especially alkalides with multiple alkali metal anions.

Electric field effects on the intermolecular interactions in water whiskers: insight from structures, energetics, and properties.

Modulation of intermolecular interactions in response to external electric fields could be fundamental to the formation of unusual forms of water, such as water whiskers. However, a detailed understanding of the nature of intermolecular interactions in such systems is lacking. In this paper, we present novel theoretical results based on electron correlation calculations regarding the nature of H-bonds in water whiskers, which is revealed by studying their evolution under external electric fields with various field strengths. We find that the water whiskers consisting of 2-7 water molecules all have a chain-length dependent critical electric field. Under the critical electric field, the most compact chain structures are obtained, featuring very strong H-bonds, herein referred to as covalent H-bonds. In the case of a water dimer whisker, the bond length of the novel covalent H-bond shortens by 25%, the covalent bond order increases by 9 times, and accordingly the H-bond energy is strengthened by 5 times compared to the normal H-bond in a (H2O)2 cluster. Below the critical electric field, it is observed that, with increasing field strength, H-bonding orbitals display gradual evolutions in the orbital energy, orbital ordering, and orbital nature (i.e., from typical π-style orbital to unusual σ-style double H-bonding orbital). We also show that, beyond the critical electric field, a single water whisker may disintegrate to form a loosely bound zwitterionic chain due to a relay-style proton transfer, whereas two water whiskers may undergo intermolecular cross-linking to form a quasi-two-dimensional water network. Overall, these results help shed new insight on the effects of electric fields on water whisker formation.

HPLC-ELSD determination of kanamycin B in the presence of kanamycin A in fermentation broth.

A novel method for the direct determination of kanamycin B in the presence of kanamycin A in fermentation broth using high performance liquid chromatography with evaporative light scattering detector (HPLC-ELSD) was developed. An Agilent Technologies C18 column was utilized, evaporation temperature of 40°C and nitrogen pressure of 3.5 bar, the optimized mobile phase was water-acetonitrile (65:35, v/v), containing 11.6 mm heptafluorobutyric acid (isocratic elution with flow rate of 0.5 mL/min) with the gain 11. Kanamycin B was eluted at 5.6 min with an asymmetry factor of 1.827. The method showed good linearity over the concentration range of 0.05 to 0.80 mg/mL for the kanamycin B (r(2) = 0.9987). The intra-day and inter-day coefficients of variation obtained from kanamycin B were less than 4.3%. Mean recovery of kanamycin B from spiked fermentation broth was 95%. The developed method was applied to the determination of kanamycin B without any interference from other constituents in the fermentation broth. This method offers simple, rapid and quantitative detection of kanamycin B.

Pan-cancer analysis of the prognostic significance and oncogenic role of GXYLT2.

Growing evidence supports an oncogenic role for glucoside xylosyltransferase 2 (GXYLT2) in a number of malignancies. To evaluate the prognostic value and oncogenic function of GXYLT2 in diverse cancer types, we analyzed sequencing data from public databases on 33 tumor tissues and their corresponding normal tissues. We found that GXYLT2 was overexpressed in a number of tumors, and that its expression was positively correlated with disease progression and mortality in several major cancer types including stomach adenocarcinoma (STAD). GXYLT2 was also linked to tumor size, grade, and the immune and molecular subtypes of STAD. GO and KEGG pathway analyses of GXYLT2 co-expressed genes in STAD suggested that GXYLT2 possibly plays a role in epithelial-mesenchymal transition, extracellular matrix production and degradation, angiogenesis, apoptosis, as well as in tumor inflammation, such as cytokine production and T cell activation. Finally, prognostic nomograms were created and validated for predicting 1, 3, and 5-year survival of patients with STAD. Our findings indicate that GXYLT2 may play a role in tumorigenesis and tumor immunity, and it may serve as a prognostic marker and potential immunotherapeutic target for STAD and some other types of cancer.

Theoretical Study of Alkaline-Earth Metal (Be, Mg, and Ca)-Substituted Aluminum Nitride Nanocages With High Stability and Large Nonlinear Optical Responses.

By replacing one Al or N atom of aluminum nitride nanocage Al12N12 with an alkaline-earth metal atom, two series of compounds, namely, M@Al12N11 and M@Al11N12 (M = Be, Mg, and Ca), were constructed and investigated in theory. The substituted effect of alkaline-earth metal on the geometric structure and electronic properties of Al12N12 is studied in detail by density functional theory (DFT) methods. The calculated binding energies, HOMO-LUMO gaps, and VIE values of these compounds reveal that they possess high stability, though the NBO and HOMO analyses show that they are also excess electron compounds. Due to the existence of diffuse excess electrons, these alkaline-earth metal-substituted compounds exhibit larger first hyperpolarizabilities (ß 0) than pure Al12N12 nanocage. In particular, these considered compounds exhibit satisfactory infrared (IR) (>1800 nm) and ultraviolet (UV) (˂ 250 nm) transparency. Therefore, these proposed excess electron compounds with high stability may be regarded as potential candidates for new UV and IR NLO molecules.

Design of a Novel Series of Hetero-Binuclear Superhalogen Anions MM'X4 - (M = Li, Na; M' = Be, Mg, Ca; X = Cl, Br).

A series of hetero-binuclear superatom motifs involving chloride/bromide ligands, that is, MM'X4 - (M = Li, Na; M' = Be, Mg, Ca; X = Cl, Br) anions, have been characterized by using many-body perturbation theory calculations. Large vertical electron detachment energies (VDEs, 5.470-6.799 eV) confirm the superhalogen identity of these anions. A larger VDE value can be obtained by introducing small M or large M' central atoms and small halogen ligand atoms. Thus, one isomer of LiCaCl4 - possesses the largest VDE value. Besides, when the extra electron is shared by all ligand atoms or three bridging ligand atoms, the isomers have relatively larger VDE values.

[The effects of a histone deacetylase (HDAC) inhibitor on endotoxin-induced endothelial cell injury].

OBJECTIVE: To examine the effects of HDAC inhibitor trichostatin A (TSA) on lipopolysaccharide (LPS) induced genes expression in cultured endothelial cells in order to understand the mechanisms involved in the protection of endothelial cells against vascular endothelium injury during endotoxemia. METHODS: Cultured EAhy926 cells (a cell line with the features of vascular endothelial cells) were treated with LPS at 100 ng/ml [the dose was chosen for minimum impact on cell survival as determined using Methyl thiazolyl tetrazolium (MTT) assay], or LPS and TSA (100 µg/ml). The expressions of toll-like receptor 4 (TLR4) and HDAC2 were measured by Western blotting 3, 6, 9, 12 and 24 hours after the beginning of the treatment. RESULTS: The expressions of TLR4 (as measured by densitometry) was found significantly higher (P< 0.01) in LPS treated cells (1.01±0.14, 1.25±0.16, 1.20±0.19) 9, 12 and 24 hours after the beginning of the treatment as compared to untreated cells (0.34±0.05); The expression of HDAC2 was also found significantly higher (P< 0.01) after LPS treatment for 12 and 24 hours (1.14±0.10, 1.20±0.04) in comparison with untreated control (0.17±0.02). In LPS+TSA treated cells, TLR4 expression (0.37±0.07) was significantly lower (P< 0.05) after 12 hours of treatment in comparison with its LPS treated counterpart (1.25±0.16), while the level of TLR4 expression stayed unchanged 24 hours after the beginning of the treatment, as compared to the result at 12 hours (0.37±0.10 vs. 1.20±0.19, P> 0.05). No visible HDAC2 expression was detected in the cells treated with LPS+TSA. CONCLUSION: LPS stimulated the increase of TLR4 and HDAC2 expression in the vascular endothelial cells studied while TSA suppress the LPS induced TLR4 and HDAC2 expression in these cells.

The behavior of the aluminum trimer when combining with different superatom clusters.

The interaction between the aluminum trimer and representative (super)halogens X (X = F, LiF2, BeF3, BF4) and (super)alkalis M (M = Li, FLi2, OLi3, NLi4) has been theoretically investigated at the MP2/6-311+(3df) level. Various geometrical structures were obtained for the resulting Al3-X and Al3-M superatom compounds, respectively. Natural bond orbital analysis reveals that the Al3 moiety exists in a cationic state in Al3-X while in an anionic state in Al3-M compounds. And the charge transfer between Al3 and (super)atoms is found to be enhanced in either polar or nonpolar solvent. The studied superatom compounds feature large bond energies, binding energies, and HOMO-LUMO gaps, which not only reflect their stability but indicate strong interactions between Al3 and (super)atoms. Although the solvent effect is not significant for the stability of Al3-X, the Al3-superalkali compounds can be better stabilized in the presence of solvent molecules. In addition, these superatom compounds exhibit aromaticity both in the gas phase and in solution.

A theoretical study on superalkali-doped nanocages: unique inorganic electrides with high stability, deep-ultraviolet transparency, and a considerable nonlinear optical response.

By doping an Al12N12 nanocage with superalkali Li3O, a series of Li3O@Al12N12 compounds were theoretically designed and investigated for the first time. Computational results reveal that these species contain diffuse excess electrons, and thus can be regarded as inorganic electrides of a new type. As expected, these proposed electrides possess considerable first hyperpolarizabilities (ß0) up to 1.86 × 10(7) au. In particular, the lowest-energy Li3O@Al12N12 exhibits high stability and excellent deep-ultraviolet transparency. Moreover, the effects of superalkali and nanocage subunits on the NLO responses of M3O@Al12N12 (M = Li, Na, K) and Li3O@X12Y12 (X = B, Al; Y = N, P) are systemically investigated. Results show that the respective substitution of Na3O and B12P12 for Li3O and Al12N12 can bring a larger ß0 for such electrides. This study may be significant in terms of providing an effective strategy to design thermally stable inorganic electrides as potential high-performance NLO molecules.

All-metal electride molecules CuAg@Ca7M (M = Be, Mg, and Ca) with multi-excess electrons and all-metal polyanions: molecular structures and bonding modes as well as large infrared nonlinear optical responses.

All-metal electride molecules, CuAg@Ca7M (M = Be, Mg and Ca), have been designed and researched in theory for the first time. In these molecules, a pull-push electron relay occurs. Unusually, the all-metal polyanions of fourfold negatively charged [Cu-Ag-Be/Mg](4-) and [Cu-Ag](4-) with 4 extra electrons gained from Ca atoms push the remaining valence electrons of the Ca atoms forming the multi-excess electrons (Ne = 10/12). Therefore, these molecules can be described as salt-like [(Ca(2+))7(CuAgM)(4-)] + 10e(-) (M = Be and Mg) and [(Ca(2+))8(CuAg)(4-)] + 12e(-). In these salt-like molecules, there are extraordinary covalent bonding modes, which include 2c-2e/3c-2e σ-bonding in the polyanions and the Ca(2+) cations sharing the diffuse multi-excess electrons. For an intriguing nonlinear optical (NLO) response, these all-metal electride molecules display large electronic first hyperpolarizabilities (ß0), thus a new class of NLO molecules, all-metal electride NLO molecules, emerge. Moreover, it is also found that manipulating the atomic number and position of M is a new strategy to enhance ß0. As a result, CuAg@Ca7Mg(1) exhibits a considerable ß0 (1.43 × 10(4) au), which is 16 times the ß0 sum of two isolated CuAg and Ca7Mg(1) subunits, and this deeply reveals the fundamental origin of the considerable ß0, namely, the multi-excess electrons generated by the subunit interaction. These all-metal electride molecules have the infrared (IR) transparent region of 1.3-6 µm, and hence are new IR NLO molecules. In addition the electronic contribution, ß0, the large effects of vibrations on the static first hyperpolarizabilities of these all-metal electride molecules are also estimated. Thus, this study opens the new research field of all-metal electride IR NLO molecules.

A new strategy for simultaneously enhancing nonlinear optical response and electron stability in novel cup-saucer⁺-cage⁻-shaped sandwich electride molecules with an excess electron protected inside the cage.

Novel cup-saucer-cage-shaped sandwich electride molecules calix[4]pyrrole···K3O(+)···e@C(n)F(n)(-), (n = 8, 10, 14, 20, and 36) with an excess electron protected inside the C(n)F(n) cage are constructed theoretically. In the sandwich structures, the below calix[4]pyrrole cup pushes the valence electron of the sandwiched superalkali atom K3O saucer, forming an excess electron, which is further pulled and protected inside the above C(n)F(n) cage, thus an electron-transfer relay occurs. In particular, owing to the unusual electron transfer, an unusual and fortunate phenomenon is discovered that increasing the C(n)F(n) cage size enhances not only the nonlinear optical response (ß0), but also the electron stability (VIP). Thus, a new strategy of simultaneously enhancing ß0 and VIP values is found for the first time, namely by increasing the C(n)F(n) cage size in novel cup-saucer-cage-shaped sandwich electride molecules, with the excess electron protected inside the cage.

ANXA2 regulates the behavior of SGC-7901 cells.

ANXA2, a member of the annexin family, is overexpressed and plays important roles in tumor development. However, the significance of ANXA2 expression in gastric carcinoma has not been clarified.To elucidate its roles in growth of gastric cancer, ANXA2 expression in SGC-7901 cells was inhibited with a designated siRNA, then cell proliferation, cell cycling, apoptosis and motility were determined by MTT assay, flow cytometry, Hoechst 33342 staining and wound healing assay, respectively. To further assess the behavior of ANXA2 deleted SGC- 7901 cells, changes of microstructures were observed under fluorescence microscopy, laser scanning confocal microscopy and electron microscopy. We found that inhibition of ANXA2 expression caused cell proliferation to decrease significantly with G1 arrest, motility to be reduced with changes in pseudopodia/filopodia structure and F-actin and ß-tubulin expression, and apoptosis to be enhanced albeit without significance. At the same time, ANXA2 deletion resulted in fewer pseudopodia/filopodia, non-stained areas were increased, contact inhibition among cells reappeared, and expression of F-actin and ß-tubulin was decreased, with induction of polymerized disassembled forms. Taken together, these data suggest that ANXA2 overexpression is important to maintain the malignancy of cancer cells, and this member of the annexin family has potential to be considered as a target for the gene therapy of gastric carcinoma.