IL-1ß promotes esophageal squamous cell carcinoma growth and metastasis through FOXO3A by activating the PI3K/AKT pathway.

Esophageal cancer is a common type of cancer that poses a significant threat to human health. While the pro-inflammatory cytokine IL-1ß has been known to contribute to the development of various types of tumors, its role in regulating esophageal cancer progression has not been extensively studied. Our studies found that the expression of IL-1ß and FOXO3A was increased in esophageal squamous cell carcinoma (ESCC). IL-1ß not only increased the proliferation, migration, and invasion of two ESCC cell lines but also promoted tumor growth and metastasis in nude mice. We also observed that IL-1ß and FOXO3A regulated the process of epithelial-mesenchymal transition (EMT) and autophagy. The PI3K/AKT pathway was found to be involved in the changes of FOXO3A with the expression level of IL-1ß. The AKT agonist (SC79) reversed the reduction of FOXO3A expression caused by the knockdown of IL-1ß, indicating that IL-1ß plays a role through the PI3K/AKT/FOXO3A pathway. Furthermore, the knockdown of FOXO3A inhibited ESCC development and attenuated the pro-cancer effect of overexpressed IL-1ß. Targeting IL-1ß and FOXO3A may be potentially valuable for the diagnosis and treatment of ESCC.

Laparoscopic assisted colectomy versus laparoscopic complete colectomy: a cost analysis.

To compare the short-term outcomes and explore the potential economic benefits of laparoscopic-assisted colectomy with extracorporeal anastomosis (LAC/EA) vs. laparoscopic complete colectomy with intracorporeal anastomosis (LCC/IA) for patients with non-metastatic resectable colon cancer. Data of patients who underwent laparoscopic hemicolectomy from January 2017 to March 2023 were collected and analyzed. Propensity score matching (PSM) analyses was carried out to minimize the selection bias. Before PSM, a total of 113 patients met the inclusion criteria (39 in the LCC/IA vs. 74 in the LAC/EA). Clinicopathologic characteristics were comparable except for the median number of removed lymph nodes (P = 0.023). LCC/IA was associated with longer operative time, less intraoperative blood loss, and shorter incision length. The rate of 30-day postoperative complications was similar, but the time to first flatus and soft diet was shorter in the LCC/IA. No deaths were reported in either group within 30 days after surgery. Costs of surgical instruments (25,945.8 ± 1,918.0 vs. 23,551.9 ± 2,665.5 RMB; P < 0.01) were higher for the LCC/IA but overall costs were similar (LCC/IA, 43,220.0 ± 4,954.0 vs. LAC/EA, 41,269.2 ± 6,685.9 RMB; P = 0.112). After PSM, 38 patients in the LCC/IA and 63 patients in the LAC/EA were compared. LCC/IA was superior in terms of intraoperative blood loss, incision length, and postoperative functional recovery. There was an extra charge of 2385.0 RMB regarding surgical instruments in the LCC/IA but the overall cost did not reach statistical significance. LCC/IA is a feasible, safe, and cost-effective surgical treatment for patients with non-metastatic resectable colon cancer.

A novel U-tied semi-manual anastomosis in totally laparoscopic colectomy.

TECHNIQUE: We describe improvements to the previously proposed "U-tied anastomosis" with the aim of broadening its indications, especially in left hemicolectomy. After bowel mobilization and vascular ligation, the proximal and distal colon were aligned in a U-shape using a ligature. An anastomosis was constructed using a linear stapler through the common enterotomies. Following resection of the bowel using laparoscopic coagulation shears, the common opening was closed using 3-0 barbed sutures. RESULTS: Eight consecutive patients underwent colectomy using the U-tied semi-manual technique between May and July 2023. In all cases, the U-tied procedures were completed using one cartridge and two sutures. No complications or mortality were observed after one month of follow-up. CONCLUSIONS: The U-tied semi-manual anastomosis is a straightforward and effective method for intracorporeal anastomosis. The simplified reconstruction technique of U-tied series, together with the minimization of technique variability, results in consistent outcomes when performed by surgeons with different levels of experience. The streamlined process enhances the homogeneity of the intracorporeal anastomosis while reducing cartridge use.

Discriminative Mechanical and Thermal Response of the H-N Bonds for the Energetic LLM-105 Molecular Assembly.

Molecular interactions in energetic materials form the key not only to the "structure stability, energy storage, ignition, and detonation" dynamics but also to the sensitivity to the loading of perturbation and the power intensity of radiation for the energetic substance, with the nature of the interactions remaining elusive. With the aid of perturbative Raman spectroscopy and the pressure-resolved density functional theory, we uncovered that the H-N bond of the intermolecular O:H-N bonds for LLM-105 shares the same negative compressibility and thermal expansivity of the H-O bond for the coupling O:H-O bond of water [Phys. Rep. 2023, 998, 1-68]. In contrast, the dangling H-N bond vibrating at a 3440 cm-1 high frequency does otherwise due to the absence of coupling interaction and the undercoordination-driven bond contraction. These findings should deepen our insight into interactions involving electron lone pairs and offer an efficient means for discriminating the performance of individual bonds.

Genetically predicted thyroid function and risk of colorectal cancer: a bidirectional Mendelian randomization study.

BACKGROUND: Observational studies have reported an association between thyroid function and colorectal cancer (CRC), with conflicting results. Elucidating the causal relationship between thyroid function and CRC facilitates the development of new preventive strategies to reduce CRC incidence. METHOD: We applied a two-sample Mendelian randomization (MR) method to evaluate the causal relationship between five thyroid-related indexes, including hyperthyroidism, hypothyroidism, thyroid stimulating hormone (TSH), free thyroxine (FT4) and basal metabolic rate (BMR), and CRC. Genome-wide association study statistics for thyroid-related phenotypes were obtained from the ThyroidOmics consortium, and summary statistics for genetic associations with CRC were obtained from the FinnGen consortium. We set a series of criteria to screen single nucleotide polymorphisms (SNPs) as instrumental variables and then performed bidirectional MR analysis, stratified analysis and extensive sensitivity analysis. Multiplicative random-effects inverse variance weighted was the primary analysis method, supplemented by weighted median and MR-Egger. RESULT: We identified 12 SNPs for hyperthyroidism, 10 SNPs for hypothyroidism, 41 SNPs for TSH, 18 SNPs for FT4, and 556 SNPs for BMR. Genetically predicted hyperthyroidism, hypothyroidism, TSH, and FT4 were not associated with CRC risk (all P > 0.05). Sensitivity analysis revealed no heterogeneity or pleiotropy. Genetically predicted BMR was significantly associated with increased CRC risk after removing outlier (OR = 1.30, P = 0.0029). Stratified analysis showed that BMR was significantly associated with colon cancer (OR = 1.33, P = 0.0074) but not rectal cancer. In the reverse analysis, there was no evidence of an effect of CRC on thyroid function (all P > 0.05). CONCLUSION: Our bidirectional MR analysis provides new insights into the relationship between thyroid function and CRC. CRC prevention may benefit from enhanced screening of high BMR populations.

A U-tie technique simplifies the intracorporeal anastomosis of totally laparoscopic colectomy.

TECHNIQUE: We propose a small improvement termed "U-tied functional end-to-end anastomosis", aiming to promote the standardization of totally laparoscopic colectomy. After bowel mobilization and vascular ligation, the proximal and distal bowel regions are tied in parallel using a ligature. Anastomosis is completed using a linear stapler through the common enterotomies. Resection of the bowel and closure of the stump are then performed simultaneously with one cartridge following the bowel anastomosis. RESULTS: Thirty patients underwent U-tied anastomosis from December 2019 to October 2022. In all cases, two cartridges were used to complete the U-tied procedure. There were no major complications or mortality within 30 days after the operation, and only one patient developed mild surgical site infection. CONCLUSIONS: The U-tied intracorporeal anastomosis is safe and effective, simplifying the reconstruction process and reducing the discrepancy between the operators' experience on the anastomotic outcomes. Thus, this procedure may promote homogeneity of intracorporeal anastomosis and reduce the use of cartridges.

Liquid biopsy on the horizon in immunotherapy of non-small cell lung cancer: current status, challenges, and perspectives.

Non-small cell lung cancer (NSCLC) is one of the most threatening malignancies to human health and life. In most cases, patients with NSCLC are already at an advanced stage when they are diagnosed. In recent years, lung cancer has made great progress in precision therapy, but the efficacy of immunotherapy is unstable, and its response rate varies from patient to patient. Several biomarkers have been proposed to predict the outcomes of immunotherapy, such as programmed cell death-ligand 1 (PD-L1) expression and tumor mutational burden (TMB). Nevertheless, the detection assays are invasive and demanding on tumor tissue. To effectively predict the outcomes of immunotherapy, novel biomarkers are needed to improve the performance of conventional biomarkers. Liquid biopsy is to capture and detect circulating tumor cells (CTCs), circulating tumor DNA (ctDNA) and exosomes in body fluids, such as blood, saliva, urine, pleural fluid and cerebrospinal fluid as samples from patients, so as to make analysis and diagnosis of cancer and other diseases. The application of liquid biopsy provides a new possible solution, as it has several advantages such as non-invasive, real-time dynamic monitoring, and overcoming tumor heterogeneity. Liquid biopsy has shown predictive value in immunotherapy, significantly improving the precision treatment of lung cancer patients. Herein, we review the application of liquid biopsy in predicting the outcomes of immunotherapy in NSCLC patients, and discuss the challenges and future directions in this field.

Low frequency lattice mode dynamics of cyclotrimethylene trinitramine (RDX) crystal studied by femtosecond time-resolved impulsive stimulated Raman scattering.

The femtosecond time-resolved impulsive stimulated Raman scattering (fs-ISRS) has been performed to study the low frequency lattice mode dynamics of the RDX crystal. Through Fourier filtering, four lattice mode dynamics is distinguished from the time-resolved spectrum. And the wavenumbers and time constants of these four lattice modes are determined by fitting their dynamic curves. The energy dispersion paths of these four lattice modes are deduced from these fitting parameters. Compared with the other three lattice modes, the lattice mode with wavenumber 30 cm-1 has a very longer life time. We consider that the excitation of this lattice mode more likely to cause the damage of the intermolecular interaction under the strong external stimulation.

G2 and S phase-expressed-1 induces chromosomal instability in esophageal squamous cell carcinoma cells and inhibits cell apoptosis through ROS/JNK signaling.

New diagnostic and therapeutic strategies are urgently needed to improve the prognosis of patients with esophageal squamous cell carcinoma (ESCC), which has high morbidity and mortality. Bioinformatics analysis revealed that cell cycle regulation related molecular G2 and S phase-expressed-1 (GTSE1) was dysregulated in ESCC. In this study, the ectopic expression of GTSE1 was verified in ESCC patients' tissues and cell lines. After overexpression or knockdown of GTSE1 using lentiviral transfection, the effects of GTSE1 on the proliferation, migration, invasion, and apoptosis of ESCC cells were detected. The contribution of GTSE1 in inducing chromosomal missegregation in cells leading to chromosome instability (CIN) has been described. Long-term existence of CIN can increase reactive oxygen species (ROS) generation in ESCC cells, followed by inhibition of apoptosis by activating the c-Jun N-terminal kinase (JNK) signaling pathway, and this inhibition could be relieved after treatment with JNK inhibitor. In vivo experiments, we also confirmed the tumor-promoting effect and mechanism of GTSE1 in ESCC using nude mice model. In this study, we demonstrated that GTSE1 induces CIN in ESCC cells, and increases intracellular ROS production, which leads to cellular oxidative stress, contributes to the activation of the JNK signaling pathway, and thereby inhibits apoptosis leading to ESCC tumorigenesis.

Aspirin Exerts Its Antitumor Effect in Esophageal Squamous Cell Carcinoma by Downregulating the Expression of ATAD2 and KIF4A.

Objective: To investigate the expression of ATPase family AAA domain-containing protein 2 (ATAD2) and kinesin family member 4A (KIF4A) in esophageal squamous cell carcinoma (ESCC) tissues and their association with clinicopathological features and to explore the role of ATAD2 in regulating KIF4A expression and biological functions in ESCC cells and the effect of aspirin on their expression. Methods: The mRNA and protein expression of ATAD2 and KIF4A in the tissues of patients with ESCC were measured by RT-qPCR and immunohistochemistry, and the correlation between the expression of mRNA and clinicopathological characteristics was analyzed. Western blot and RT-qPCR were used to detect the interference efficiency and KIF4A expression after si-ATAD2 transfection in EC109 and KYSE30 cells. CCK-8 and Transwell assay were performed to investigate the effects of ATAD2 and aspirin on proliferation, migration, and invasion of ESCC cells. The effect of aspirin on the expression of ATAD2 and KIF4A in ESCC cells was measured by RT-qPCR and Western blot. Results: The expression of ATAD2 and KIF4A was upregulated in ESCC tissues, and both were correlated with the differentiation grades and lymph node metastasis. Knockdown of ATAD2 in ESCC cells significantly inhibited cell proliferation, migration, and invasion. Compared to the negative control group, the proliferation, migration, and invasion ability of ESCC cells in the aspirin-treated groups were decreased, and the expression of ATAD2 and KIF4A in ESCC cells was decreased after treating with aspirin for 48 h. Conclusion: The expression levels of ATAD2 and KIF4A are elevated in ESCC. ATAD2 promotes proliferation, migration, and invasion of ESCC cells by regulating KIF4A. Aspirin can inhibit the malignant behavior of ESCC cells by downregulating ATAD2 and KIF4A.

Quantifying the Improvement in Dielectric Properties of BaSrTiO3-Based Ceramics by Adding MgO.

Barium titanate (BaTiO3, BT) is the main raw material of multilayer ceramic capacitors. As thinner layers of dielectric elements require smaller BT grain diameters, BT-MgO composites have been widely studied owing to the plasticity of MgO and its inhibition of grain growth. However, further improvements of the dielectric properties of the BT-MgO system are still urgently needed. Herein, composite ceramics of Ba0.7Sr0.3Ti0.9925Tm0.01O3 (BST)-x mol% MgO (x = 1, 2, 3, 4, 5) were prepared. The dielectric constant of BST-1 mol% MgO at room temperature was approximately 3800, which was 1/3 times higher than that of BT-MgO composite ceramics. The dielectric loss was less than 0.004 and 2/3 that of BT-MgO composite ceramics. The Curie temperature of BST doped with MgO was below 0 °C. The anomalous increase in dielectric constant was caused by the co-doping of Sr and Tm with BT, while the reduced dielectric loss was due to the uniform dispersion of MgO at grain boundaries, which hinders grain growth. The Curie temperature shift was mainly due to accumulated oxygen vacancies. Thus, this work provides new solutions to further improve the dielectric properties of the BT-MgO system, including changing the doping elements and adjusting the doping ratio.

Thermal properties of energetic materials from quasi-harmonic first-principles calculations.

The structure and properties at a finite temperature are critical to understand the temperature effects on energetic materials (EMs). Combining dispersion-corrected density functional theory with quasi-harmonic approximation, the thermodynamic properties for several representative EMs, including nitromethane, PETN, HMX, and TATB, are calculated. The inclusion of zero-point energy and temperature effect could significantly improve the accuracy of lattice parameters at ambient condition; the deviations of calculated cell volumes and experimental values at room temperature are within 0.62%. The calculated lattice parameters and thermal expansion coefficients with increasing temperature show strong anisotropy. In particular, the expansion rate (2.61%) of inter-layer direction of TATB is higher than intra-layer direction and other EMs. Furthermore, the calculated heat capacities could reproduce the experimental trends and enrich the thermodynamic data set at finite temperatures. The predicted isothermal and adiabatic bulk moduli could reflect the softening behavior of EMs. These results would fundamentally provide a deep understanding and serve as a reference for the experimental measurement of the thermodynamic parameters of EMs.

Vibrational energy redistribution in crystalline nitromethane simulated by ab initio molecular dynamics.

Ab initio molecular dynamics simulations (AIMD) are systematically performed to study the Vibrational Energy Redistribution (VER) in solid nitromethane (NM) by combining normal mode decomposition and short-time Fourier transform technique. After the selective excitations of all fourteen intramolecular vibrational modes above 400 cm-1, four three-dimensional (3D) excitation and detected vibrational spectra are obtained. The evolution of the kinetic energy proportion of all vibrations are also given and discussed quantitatively. These results show that, as the daughter modes, NO2 symmetric stretches, CH3 stretches and bends are usually excited quickly and relatively conspicuously compared with the other vibrations. Interestingly, we found that, although the stretching vibration of the CN bond which is a bridge between the methyl and nitro group can not respond immediately to the selective excitations, it always accumulates the vibrational energy slowly and steadily. Then, the underlying mechanisms are discussed based on the response of vibrational modes in both the time and frequency domain. As a result, we found that anharmonic transfers following symmetry rules which involve the couplings assisted by the overtones and rotations, as well as the transfers among the adjacent modes, play important roles in the VER of solid NM.

Elucidating the Coupling Mechanisms of Rapid Intramolecular Vibrational Energy Redistribution in Nitromethane: Ab Initio Molecular Dynamics Simulation.

Ab initio molecular dynamics simulations are presented to investigate the intramolecular vibrational energy redistribution (IVR) of an isolated nitromethane molecule. A number of IVR processes are simulated by monitoring the kinetic energy of vibrational modes under selective low-lying vibrational excitations from their ground states (Δν = 1 or 2). Evolution of the normal-mode kinetic energy gives the ultrafast energy transfer processes from parent modes to daughter modes intuitively. From the ultrafast vibrational transfer made by Fourier transformation of the time-dependent normal-mode kinetic energy, we can capture that the symmetry of the normal modes plays an important role in the anharmonic coupling between the vibrational modes. The results show three symmetry-dependent coupling mechanisms: direct symmetric coupling, overtone-assisted coupling, and rotation-assisted coupling. Furthermore, the calculated efficiencies of IVR also coincide with these mechanisms.

Ab initio molecular dynamics simulation of vibrational energy redistribution of selective excitation of C-H stretching vibrations for solid nitromethane.

Vibrational energy redistribution (VER) of energetic materials plays an important role in transferring the injected energy to the hot spots, but it is extremely challenging to understand the mechanism of VER from experimental or theoretical studies. Here, we combined nonequilibrium molecular dynamics with density functional theory to study the processes of VER for solid nitromethane after the selective excitation of the C-H stretching vibration. The VER processes are traced by monitoring the normal-mode kinetic energies of both excited and unexcited vibrations. To explore the underlying VER mechanism, we also analyzed the spectral energy density for the normal mode, obtained from the squared modulus of the short-time Fourier transition of their normal mode momentum. The results showed that the simulated VER progress was reproduced well compared with the previous 3D IR-Raman experiments of liquid nitromethane. Interestingly, the symmetric dependence of the coupling mechanism between the normal modes has been found.

Correction: Significance of hydrogen bonding networks in the proton-coupled electron transfer reactions of photosystem II from a quantum-mechanics perspective.

Correction for 'Significance of hydrogen bonding networks in the proton-coupled electron transfer reactions of photosystem II from a quantum-mechanics perspective' by Jun Chai et al., Phys. Chem. Chem. Phys., 2019, 21, 8721-8728.

Significance of hydrogen bonding networks in the proton-coupled electron transfer reactions of photosystem II from a quantum-mechanics perspective.

The photosynthetic protein complex, photosystem II (PSII), conducts the light-driven water-splitting reaction with unrivaled efficiency. Proton-coupled electron transfer (PCET) reactions at the redox-active tyrosine residues are thought to play a critical role in the water-splitting chemistry. Addressing the fundamental question as to why the tyrosine residue, YZ, is kinetically competent in comparison to a symmetrically placed tyrosine residue, YD, is important for the elucidation of the mechanism of PCET in the water-splitting reaction of PSII. Here, using all-quantum-mechanical calculations we study PCET at the YZ and YD residues of PSII. We find that when YZ is in its protein matrix under physiological conditions, the HOMO of YZ constitutes the HOMO of the whole system. In contrast, the HOMO of YD is buried under the electronic states localized elsewhere in the protein matrix and PCET at YD requires the transfer of the phenolic proton, which elevates the HOMO of YD to become the HOMO of the whole system. This leads to the oxidation of YD, albeit on a slower timescale. Our study reveals that the key differences between the electronic structure of YZ and YD are primarily determined by the protonation state of the respective hydrogen-bonding partners, D1-His190 and D2-His189, or more generally by the H-bonding network of the protein matrix.

Tracking Intramolecular Vibrational Redistribution in Polyatomic Small-Molecule Liquids by Ultrafast Time-Frequency-Resolved CARS.

Selective excitation of C-H stretching vibrational modes, detection of intramolecular vibrational energy redistribution (IVR), and vibrational modes coupling in the electronic ground state of benzene are performed by using femtosecond time- and frequency-resolved coherent anti-Stokes Raman scattering (CARS) spectroscopy. Both of the parent modes in the Raman-active bands are coherently excited by an ultrafast stimulated Raman pump, giving initial excitations of 3056 cm-1 (A1g) and 3074 cm-1 (E2g) and subsequent IVR from the parent modes to daughter modes of 1181 and 992 cm-1, and the coherent vibrational coupling of the relevant modes is tracked. The directionality and selectivity of IVR and coherent coupling among all of the relevant vibrational modes are discussed in the view of molecular symmetry.

Visualizing Intramolecular Vibrational Redistribution in Cyclotrimethylene Trinitramine (RDX) Crystals by Multiplex Coherent Anti-Stokes Raman Scattering.

The femtosecond time-resolved multiplex coherent anti-Stokes Raman scattering (CARS) technique has been performed to investigate intramolecular vibrational redistribution (IVR) through vibrational couplings in 1,3,5-trinitro-1,3,5-triazacyclohexane (RDX) molecules. In the multiplex CARS experiment, the supercontinuum (SC) was used as broad-band Stokes light to coherently and collectively excite multiple vibrational modes, and quantum beats arising from vibrational couplings among these modes were observed. The IVR of RDX is visualized by a topological graph of these vibrational couplings, and with analysis of the topological graph, two vibrational modes, both of which are assigned to ring bending, are confirmed to have coupling interactions with most of the other vibrational modes and are considered to have a tendency of energy transfer with these vibrational modes. We suggest that the mode at 466 cm-1 is a portal of energy transfer from outside to inside of the RDX molecule and the mode at 672 cm-1 is an important transit point of energy transfer in the IVR.

Phase diagrams for clathrate hydrates of methane, ethane, and propane from first-principles thermodynamics.

Natural gas hydrates are inclusion compounds composed of major light hydrocarbon gaseous molecules (CH4, C2H6, and C3H8) and a water clathrate framework. Understanding the phase stability and formation conditions of natural gas hydrates is crucial for their future exploitation and applications and requires an accurate description of intermolecular interactions. Previous ab initio calculations on gas hydrates were mainly limited by the cluster models, whereas the phase diagram and equilibrium conditions of hydrate formation were usually investigated using the thermodynamic models or empirical molecular simulations. For the first time, we construct the chemical potential phase diagrams of type II clathrate hydrates encapsulated with methane/ethane/propane guest molecules using first-principles thermodynamics. We find that the partially occupied structures (136H2O·1CH4, 136H2O·16CH4, 136H2O·20CH4, 136H2O·1C2H6, and 136H2O·1C3H8) and fully occupied structures (136H2O·24CH4, 136H2O·8C2H6, and 136H2O·8C3H8) are thermodynamically favorable under given pressure-temperature (p-T) conditions. The theoretically predicted equilibrium pressures for pure CH4, C2H6 and C3H8 hydrates at the phase transition point are consistent with the experimental data. These results provide valuable guidance for establishing the relationship between the accurate description of intermolecular noncovalent interactions and the p-T equilibrium conditions of clathrate hydrates and other molecular crystals.