Colon Sparing Endoscopic Full-Thickness Resection for Advanced Colorectal Lesions: Is It Time for Global Adoption?

The majority of colon lesions are <10 mm in size and are easily resected by endoscopists with appropriate basic training. Lesions ≥10 mm in size are difficult to remove technically and are associated with higher rates of incomplete resection. Currently, the main endoscopic approaches include endoscopic mucosal resection (EMR) for lesions without submucosal invasion, and endoscopic submucosal dissection (ESD) for relatively larger lesions involving the superficial submucosal layer. Both of these approaches have limitations, EMR cannot reliably ensure complete resection for larger tumors and recurrence is a key limitation. ESD reliably provides complete resection and an accurate pathological diagnosis but is associated with risk such as perforation or bleeding. In addition, both EMR and ESD may be ineffective in treating subepithelial lesions that extend beyond the submucosa. Endoscopic full-thickness resection (EFTR) is an emerging innovative endoscopic therapy which was developed to overcome the limitations of EMR and ESD. Advantages include enabling a transmural resection, complete resection of complex colorectal lesions involving the mucosa to the muscularis propria. Recent studies comparing EFTR with current resection techniques and radical surgery for relatively complicated and larger lesion have provided promising results. If the current trajectory of research and development is maintained, EFTR will likely to become a strong contender as an alternative standard of care for advanced colonic lesions. In the current study we aimed to address this need, and highlighted the areas of future research, while stressing the need for multinational collaboration provide the steppingstone(s) needed to bring EFTR to the mainstream.

Theoretical study of electronic and nonlinear optical properties of novel graphenylene-based materials with donor-acceptor frameworks.

A new functionalized graphenylene-based structure was designed by adsorbing of alkali metals M3 and superalkali M3O (M = Li, Na, K) on graphenylene (BPC) surface. The spectral data show that the spectral properties of the M3O@BPC system are very similar because the two-dimensional material plays a major role in the main transition. However, for M3@BPC system, the spectral shapes of the three systems show significant changes compared to each other because the different alkali metals play a major role in the main transition process. The calculation results show that the introduction of superalkali does not significantly increase the first polarizability; however, the introduction of alkali metals can obtain considerable nonlinear optical materials. For M3@BPC system, the first hyperpolarizability increases significantly when heavier alkali metal is introduced into the two-dimensional structure, which is found to be 866,290.9 au for K3@ BPC. A two-level model and first hyperpolarizability density can explain the large first polarizability of these systems.

Calycosin attenuates severe acute pancreatitis-associated acute lung injury by curtailing high mobility group box 1 - induced inflammation.

BACKGROUND: Acute lung injury (ALI) is a common and life-threatening complication of severe acute pancreatitis (SAP). There are currently limited effective treatment options for SAP and associated ALI. Calycosin (Cal), a bioactive constituent extracted from the medicinal herb Radix Astragali exhibits potent anti-inflammatory properties, but its effect on SAP and associated ALI has yet to be determined. AIM: To identify the roles of Cal in SAP-ALI and the underlying mechanism. METHODS: SAP was induced via two intraperitoneal injections of L-arg (4 g/kg) and Cal (25 or 50 mg/kg) were injected 1 h prior to the first L-arg challenge. Mice were sacrificed 72 h after the induction of SAP and associated ALI was examined histologically and biochemically. An in vitro model of lipopolysaccharide (LPS)-induced ALI was established using A549 cells. Immunofluorescence analysis and western blot were evaluated in cells. Molecular docking analyses were conducted to examine the interaction of Cal with HMGB1. RESULTS: Cal treatment substantially reduced the serum amylase levels and alleviated histopathological injury associated with SAP and ALI. Neutrophil infiltration and lung tissue levels of neutrophil mediator myeloperoxidase were reduced in line with protective effects of Cal against ALI in SAP. Cal treatment also attenuated the serum levels and mRNA expression of pro-inflammatory cytokines tumor necrosis factor-α, interleukin-6, IL-1ß, HMGB1 and chemokine (CXC motif) ligand 1 in lung tissue. Immunofluorescence and western blot analyses showed that Cal treatment markedly suppressed the expression of HMGB1 and phosphorylated nuclear factor-kappa B (NF-κB) p65 in lung tissues and an in vitro model of LPS-induced ALI in A549 cells suggesting a role for HGMB1 in the pathogenesis of ALI. Furthermore, molecular docking analysis provided evidence for the direct interaction of Cal with HGMB1. CONCLUSION: Cal protects mice against L-arg-induced SAP and associated ALI by attenuating local and systemic neutrophil infiltration and inflammatory response via inhibition of HGMB1 and the NF-κB signaling pathway.

Serum soluble suppression of tumorigenicity 2 as a novel inflammatory marker predicts the severity of acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is an inflammatory disease in which the regulatory pathway is complex and not well understood. Soluble suppression of tumorigenicity 2 (sST2) protein receptor functions as a decoy receptor for interleukin (IL)-33 to prevent IL-33/suppression of tumorigenicity 2L (ST2L)-pathway-mediated T helper (Th)2 immune responses. AIM: To investigate the role of sST2 in AP. METHODS: We assessed the association between sST2 and severity of AP in 123 patients enrolled in this study. The serum levels of sST2, C-reactive protein (CRP) and Th1- and Th2-related cytokines, including interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-2, IL-4, IL-5 and IL-13, were measured by highly sensitive ELISA, and the severity of AP in patients was evaluated by the 2012 Atlanta Classification Criteria. RESULTS: Serum sST2 levels were significantly increased in AP patients, and further, these levels were significantly elevated in severe AP (SAP) patients compared to moderately severe AP (MSAP) and mild AP (MAP) patients. Logistic regression showed sST2 was a predictor of SAP [odds ratio (OR): 1.003 (1.001-1.006), P = 0.000]. sST2 cutoff point was 1190 pg/mL, and sST2 above this cutoff was associated with SAP. sST2 was also a predictor of any organ failure and mortality during AP [OR: 1.006 (1.003-1.009), P = 0.000, OR: 1.002 (1.001-1.004), P = 0.012, respectively]. Additionally, the Th1-related cytokines IFN-γ and TNF-α in the SAP group were higher and the Th2-related cytokine IL-4 in the SAP group was significantly lower than those in MSAP and MAP groups. CONCLUSION: sST2 may be used as a novel inflammatory marker in predicting AP severity and may regulate the function and differentiation of IL-33/ST2-mediated Th1 and Th2 Lymphocytes in AP homeostasis.

Galangin ameliorates severe acute pancreatitis in mice by activating the nuclear factor E2-related factor 2/heme oxygenase 1 pathway.

Acute pancreatitis (AP) is a common serious acute condition of the digestive system that remains a clinical challenge. Severe acute pancreatitis (SAP) in particular is characterized by high morbidity and mortality. The present study was designed to investigate the protective effect of Galangin (Gal), a natural flavonol obtained from lesser galangal, on L-arginine-induced SAP in mice and in AR42J cells. Amylase and lipase activities were measured and the histopathology of the pancreas, lung, and kidney was evaluated. Inflammation and oxidative stress were assessed using ELISA, western blotting, RT-PCR, and immunohistochemistry. Gal was shown to reduce proinflammatory cytokine production and reactive oxygen species (ROS) generation in vivo and in vitro. L-arginine treatment reduced the expression of components of the nuclear factor E2-related factor 2 (Nrf2) signaling pathway and the downstream protein heme oxygenase-1 (HO-1) in mice, whereas Gal increased their expression. Furthermore, the Nrf2/HO-1 pathway inhibitor brusatol prevented the anti-inflammatory and antioxidant effects of Gal in mice with SAP. Taken together, our results imply that Gal has protective effects in L-arginine-induced SAP that are induced by the upregulation of the Nrf2/HO-1 pathway, which has anti-inflammatory and antioxidant effects. Thus, Gal may represent a promising treatment for SAP.

Theoretical study of the mixed π-conjugated bridge effect on the nonlinear optical properties of corannulene derivative.

A new series of corannulene derivatives with two mixed π-conjugated bridge have been theoretically designed and investigated by means of density functional theory. It is found that all molecules exhibit large energy gaps. The holes and electrons analysis show that charge transfer from long-chain connected with NH2 to long-chain connected with NO2. The small transition energy brings corannulene derivatives larger first hyperpolarizabilities. Furthermore, the polarization scan of the hyper-Rayleigh scattering (HRS) intensity indicates that all studied compounds belong to dipolar characteristic. The results indicate that employing two mixed π-conjugated bridge can significantly increase the first hyperpolarizability.

Active Enhancer Assessment by H3K27ac ChIP-seq Reveals Claudin-1 as a Biomarker for Radiation Resistance in Colorectal Cancer.

BACKGROUND: Colorectal cancer (CRC) represents the third most common malignant tumor in the worldwide. Radiotherapy is the common therapeutic treatment for CRC, but radiation resistance is often encountered. ChIP-seq of Histone H3K27 acetylation (H3K27ac) has revealed enhancers that play an important role in CRC. This study examined the relationship between an active CRC enhancer and claudin-1 (CLDN1), and its effect on CRC radiation resistance. METHODS: The target CRC genes of active enhancers were obtained from public H3K27ac ChIP-seq, and the genes highly expressed in radio-resistant CRC were screened and intersected with enhancer-driven genes. The clinical roles of CLDN1 in radiation resistance were examined using the t-test, standard mean deviation (SMD), summary receiver operating characteristic curve and Kaplan-Meier curves. The co-expressed genes of CLDN1 were calculated using Pearson Correlation analysis, and Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes and Gene Set Variation Analysis (GSVA) analyses were used to examine the molecular mechanisms of CLDN1. RESULTS: Total 13 703 CRC genes were regulated by enhancers using 58 H3K27ac ChIP-seq. Claudin-1 (CLDN1) was enhancer-driven and notably up-regulated in CRC tissues compared to non-CRC controls, with a SMD of 3.45 (95 CI % = .56-4.35). CLDN1 expression was increased in radiation-resistant CRC with a SMD of .42 (95% CI = .16-.68) and an area under the curve of .74 (95% CI = .70-.77). The cell cycle and immune macrophage levels were the most significant pathways associated with CLDN1. CONCLUSION: CLDN1 as an enhancer-regulated gene that can boost radiation resistance in patients with CRC.

Designing a novel material with considerable nonlinear optical responses based on the bicorannulenyl molecule.

In this work, a series of molecules decorated with Li atom and donor/acceptor have been theoretically designed based on bicorannulenyl molecule, where incorporating Li and different substitution are used as an effective strategy for enhancing nonlinear optical response. The mixed method is constructed through incorporating the Li and NO2/NH2 substitution. To ensure accuracy, results were compared with another two functionals. As expected, data from three different functional approximations indicate that these molecules have large first hyperpolarizability. The calculation proves that these molecules exhibit large first hyperpolarizability in the range of 1956-37,758 au. For Li doped systems, by analyzing NBO, charge transfer occurs in studied molecules, which helps to get large nonlinear optical response. It is revealed that when Li atom is introduced into the molecule with only NO2/NH2 substitution, the first hyperpolarizability increases significantly. Compared with Li doped and NO2 substitution, incorporating Li and NH2 substitution can be more powerful in increasing the first hyperpolarizabilities of bicorannulenyl molecule. In addition, the number of NH2 substitutions can more effectively enhance the first hyperpolarizability. We hope that this study could provide a new idea for designing nonlinear optical materials using bicorannulenyl molecule.

Computational study of the NO, SO2, and NH3 adsorptions on fragments of 3N-graphene and Al/3N graphene.

The adsorption properties of common gas molecules (NO, NH3, and SO2) on the surface of 3N-graphene and Al/3N graphene fragments are investigated using density functional theory. The adsorption energies have been calculated for the most stable configurations of the molecules on the surface of 3N-graphene and Al/3N graphene fragments. The adsorption energies of Al/3N graphene-gas systems are -220.5 kJ mol-1 for Al/3NG-NO, -111.9 kJ mol-1 for Al/3NG-NH3, and -347.7 kJ mol-1 for Al/3NG-SO2, respectively. Compared with the 3N-graphene fragment, the Al/3N graphene fragment has significant adsorption energy. Furthermore, the molecular orbital, density of states, and electron densities distribution were used to explore the interaction between these molecules and the surface. We found that orbital hybridization exists between these molecules and the Al/3N graphene surface, which indicates that doping Al significantly increases the interaction between the gas molecules and Al/3N graphene. In addition, compared with Li, Al can more powerfully enhance adsorption of the 3N-graphene fragment. The results indicate that Al/3N graphene can be viewed as a new nanomaterial adsorbent for NO, NH3, and SO2.

Substituent effects on the electronic structures and nonlinear optical properties of Li-doped nano-carbon bowl.

A series of Li-corannulene-(NH2)n and Li-corannulene-(NO2)n (n = 1, 2, 5) compounds have been theoretically designed and investigated using density functional theory. In this work, two models are systematically investigated to explore the important factors for enhancing the static first hyperpolarizability by introducing the substitution group. It is revealed that energy gaps (Egap) between highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) of all compounds are in the range of 4.149-4.934 eV. Different DFT methods are adopted to calculate polarizabilities and the first hyperpolarizabilities of Li-corannulene-(NH2)n and Li-corannulene-(NO2)n (n = 1, 2, 5) compounds. It is revealed that polarizability values of the systems increase with increasing number of NH2/NO2 substitution group. Moreover, it is found that the first hyperpolarizabilities of Li-corannulene-(NO2)n are larger than those of Li-corannulene-(NH2)n, which can be attributed to the lower transition energies. In contrast to the NH2 substitution group, NO2 substitution group can be more powerful in increasing the first hyperpolarizability of Li-doped corannulene. We hope that this study can provide a new idea for designing nonlinear optical materials using the NH2 and NO2 groups.

Theoretical study of the structures and first hyperpolarizabilities of C60Cl n and Li@C60Cl n (n = 4, 6, 8, 10).

We recently reported (Song Y-D et al., 2016, J Mol Model 22:50) that doping with Li greatly affects the static first hyperpolarizability of C60Cl2. In this work, with a view to creating nonlinear optical materials with high thermodynamic stability and wide transparent regions, a series of Li@C60Cl n (n = 4, 6, 8, 10) were designed. The structures, electrostatic potentials, electronic structures, absorption spectra, and linear and nonlinear optical properties of C60Cl n and Li@C60Cl n were systematically investigated using density functional theory (DFT) methods. The results of our calculations indicated that the stability of these molecules decreases in the order Li@C60Cl10 > Li@C60Cl8 > Li@C60Cl6 > Li@C60Cl4. It is clear that the number of Cl atoms greatly influences the stability of Li@C60Cl n . Li@C60Cl n showed greater thermodynamic stability than Li@C60Cl2. We also investigated the first hyperpolarizabilities of Li@C60Cl n and found them to be 2973, 3640, 4307, and 2627 au for n = 4, 6, 8, and 10, respectively-higher than that of Li@C60Cl2. Finally, we noted that the transparent region could be modulated by increasing the number of Cl atoms: Li@C60Cl n possess wider transparent regions than that of Li@C60Cl2. We therefore believe that this study has highlighted an effective method for designing nonlinear optical materials with high thermodynamic stability and wide transparent regions.

The encapsulated lithium effect on the first hyperpolarizability of C60Cl2 and C60F2.

In this paper, we report a study on the structure and first hyperpolarizability of C60Cl2 and C60F2. The calculation results show that the first hyperpolarizabilities of C60Cl2 and C60F2 were 172 au and 249 au, respectively. Compared with the fullerenes, the first hyperpolarizability of C60Cl2 increased from 0 au to 172 au, while the first hyperpolarizability of C60F2 increased from 0 au to 249 au. In order to further increase the first hyperpolarizability of C60Cl2 and C60F2, Li@C60Cl2 and Li@C60F2 were obtained by introducing a lithium atom to C60Cl2 and C60F2. The first hyperpolarizabilities of Li@C60Cl2 and Li@C60F2 were 2589 au and 985 au, representing a 15-fold and 3.9-fold increase, respectively, over those of C60Cl2 and C60F2. The transition energies of four molecules (C60Cl2, Li@C60Cl2, C60F2, Li@C60F2) were calculated, and were found to be 0.17866 au, 0.05229 au, 0.18385 au, and 0.05212 au, respectively. A two-level model explains why the first hyperpolarizability increases for Li@C60Cl2 and Li@C60F2.

How lithium atoms affect the first hyperpolarizability of BN edge-doped graphene.

How do lithium atoms affect the first hyperpolarizability (ß0) of boron-nitrogen (BN) edge-doped graphene. In this work, using pentacene as graphene model, Lin@BN-1 edge-doped pentacene and Lin@BN-2 edge-doped pentacene (n = 1, 5) were designed to study this problem. First, two models (BN-1 edge-doped pentacene, and BN-2 edge-doped pentacene ) were formed by doping the BN into the pentacene with different order, and then Li@BN-1 edge-doped pentacene and Li@ BN-2 edge-doped pentacene were obtained by substituting the H atom in BN edge-doped pentacene with a Li atom. The results show that the first hyperpolarizabilities of BN-1 edge-doped pentacene and Li@BN-1 edge-doped pentacene were 4059 a.u. and 6249 a.u., respectively; the first hyperpolarizabilities of BN-2 edge-doped pentacene and Li@BN-2 edge-doped pentacene were 2491 a.u. and 4265 a.u., respectively. The results indicate that the effect of Li substitution is to greatly increase the ß0 value. To further enhance the first hyperpolarizability, Li5@ BN-1 edge-doped pentacene and Li5@BN-2 edge-doped pentacene were designed, and were found to exhibit considerably larger first hyperpolarizabilities (ß0) (12,112 a.u. and 7921a.u., respectively). This work may inspire further study of the nonlinear properties of BN edge-doped graphene.