Phloridzin reduces synovial hyperplasia and inflammation in rheumatoid arthritis rat by modulating mTOR pathway.

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease and management of it still a challenge. Given report evaluates protective effect of phlorizin on RA and also postulates the molecular mechanism of its action. Bovine type II collagen (CIA) and Freund's incomplete adjuvant (1:1 and 1 mg/ml) was administered on 1st and 8th day of protocol to induce RA in rats and treatment with phlorizin 60 and 120 mg/kg was started after 4th week of protocol. Level of inflammatory cytokines and expression of proteins were estimated in phlorizin treated RA rats. Moreover in-vitro study was performed on Fibroblast-like synoviocytes (FLSs) and effect of phlorizin was estimated on proliferation, apoptosis and expression of mTOR pathway protein after stimulating these cell lines with Tumour Necrosis Factor alpha (TNF-α). Data of study suggest that phlorizin reduces inflammation and improves weight in CIA induced RA rats. Level of inflammatory cytokines in the serum and expression of Akt/PI3K/mTOR proteins in the join tissue was reduced in phlorizin treated RA rats. Phlorizin also reported to reverse the histopathological changes in the joint tissue of RA rats. In-vitro study supports that phlorizin reduces proliferation and no apoptotic effect on TNF-α stimulated FLSs. Expression of Akt/PI3K/mTOR proteins also downregulated in phlorizin treated TNF-α stimulated FLSs. In conclusion, phlorizin protects inflammation and reduces injury to the synovial tissues in RA, as it reduces autophagy by regulating Akt/PI3K/mTOR pathway.

Phlorizin Regulates Synovial Hyperplasia and Inflammation in Rats With Rheumatoid Arthritis by Regulating the mTOR Pathway.

BACKGROUND/AIM: Rheumatoid arthritis (RA) is an inflammatory autoimmune disease, and management of it is still a challenge. The present investigation assessed the potential preventive effect of phlorizin on rats with RA. MATERIALS AND METHODS: A total of 40 healthy Wistar rats were used for this study. Bovine type II collagen and Freund's incomplete adjuvant (1:1 and 1 mg/ml) were administered on days 1 and 8 of the protocol to induce RA in rats; treatment with phlorizin at 60 or 120 mg/kg was started after the 4th week of the protocol, and its effect on inflammation, level of inflammatory cytokines, and expression of proteins were estimated in RA rats. Moreover, an in vitro study was performed on fibroblast-like synoviocytes (FLSs), and the effects of phlorizin on proliferation, apoptosis, and expression of the mechanistic target of rapamycin kinase pathway protein after stimulating these cells with tumor necrosis factor α (TNF-α) were estimated. RESULTS: The data obtained from the study indicate that phlorizin has the potential to mitigate inflammation and enhance weight management in rats with RA induced by bovine type II collagen (CII). The level of inflammatory cytokines in the serum and the expression of protein kinase B (AKT), phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), and mechanistic target of rapamycin kinase (mTOR) proteins in the joint tissue were reduced in phlorizin-treated rats with RA. In this investigation, phlorizin was shown to reverse the histological abnormalities in the joint tissue of rats with RA. The in-vitro study showed that phlorizin reduced proliferation and had no apoptotic effect on TNF-α-stimulated FLSs. Expression of AKT, PI3K, and mTOR proteins was also down-regulated in phlorizin-treated TNF-α-stimulated FLSs. CONCLUSION: Phlorizin protects against inflammation and reduces injury to synovial tissues in RA by modulating the AKT/PI3K/mTOR pathway.

Photoionization and Dissociative Photoionization of Acetaldehyde in the 10.0-13.7†eV Range by Synchrotron Photoelectron Photoion Coincidence Spectroscopy.

Photoionization and dissociative photoionization of acetaldehyde (CH3CHO) in the 10.0-13.7 eV energy range are studied by using synchrotron radiation double imaging photoelectron photoion coincidence spectroscopy (i2PEPICO). The X2A' and A2A" electronic states of CH3CHO+ as well as the Franck-Condon gap region between these two states have been populated with several vibrational sequences and assigned in the high-resolution slow photoelectron spectrum (SPES). The adiabatic ionization energies (AIEs) of the X2A' and A2A" states are measured at 10.228±0.006 and 12.52±0.05 eV, respectively. The present results show that the X2A' state is a stable state while the A2A" state is fully dissociative to produce CH3CO+, CHO+ and CH4 + fragment ions. The 0 K appearance energies (AE0K) of CH3CO+ and CHO+ fragment ions are determined through the modeling of the breakdown diagram, i. e., AE0K(CH3CO+)=10.89±0.01 eV (including a reverse barrier of ~0.19 eV) and AE0K(CHO+)=11.54±0.05 eV. In addition, the dissociation mechanisms of CH3CHO+ including statistical dissociation, direct bond breaking and isomerization are discussed with the support of the calculated dissociation limits and transition state energies.

CO Cofeeding Affects Product Distribution in CH3Cl Coupling over ZSM-5 Zeolite: Pressure Twists the Plot.

C1 coupling reactions over zeolite catalysts are central to sustainable chemical production strategies. However, questions persist regarding the involvement of CO in ketene formation, and the impact of this elusive oxygenate intermediate on reactivity patterns. Using operando photoelectron photoion coincidence spectroscopy (PEPICO), we investigate the role of CO in methyl chloride conversion to hydrocarbons (MCTH), a prospective process for methane valorization with a reaction network akin to methanol to hydrocarbons (MTH) but without oxygenate intermediates. Our findings reveal the transformative role of CO in MCTH at the low pressures, inducing ketene formation in MCTH and boosting olefin production, confirming the Koch carbonylation step in the initial stages of C1 coupling. We uncover pressure-dependent product distributions driven by CO-induced ketene formation, and its subsequent desorption from the zeolite surface, which is enhanced at low pressure. Inspired by the above results, extension of the co-feeding approach to CH3OH as another simple oxygenate showcases the additional potential for improved catalyst stability in MCTH at ambient pressure.

Predicting Gas Adsorption without the Knowledge of Pore Structures: A Machine Learning Method Based on Classical Density Functional Theory.

Predicting gas adsorption from the pore structure is an intuitive and widely used methodology in adsorption. However, in real-world systems, the structural information is usually very complicated and can only be approximately obtained from the characterization data. In this work, we developed a machine learning (ML) method to predict gas adsorption form the raw characterization data of N2 adsorption. The ML method is modeled by a convolutional neural network and trained by a large number of data that are generated from a classical density functional theory, and the model gives a very accurate prediction of Ar adsorption. Though the training set is limited to modeling slit pores, the model can be applied to three-dimensional structured pores and real-world materials. The good agreements suggest that there is a universal relationship among adsorption isotherms of different adsorbates, which could be captured by the ML model.

Photoion Mass-Selected Threshold Photoelectron Spectroscopy to Detect Reactive Intermediates in Catalysis: From Instrumentation and Examples to Peculiarities and a Database.

Photoion mass-selected threshold photoelectron spectroscopy (ms-TPES) is a synchrotron-based, universal, sensitive, and multiplexed detection tool applied in the areas of catalysis, combustion, and gas-phase reactions. Isomer-selective vibrational fingerprints in the ms-TPES of stable and reactive intermediates allow for unequivocal assignment of spectral carriers. Case studies are presented on heterogeneous catalysis, revealing the role of ketenes in the methanol-to-olefins process, the catalytic pyrolysis mechanism of lignin model compounds, and the radical chemistry upon C-H activation in oxyhalogenation. These studies demonstrate the potential of ms-TPES as an analytical technique for elucidating complex reaction mechanisms. We examine the robustness of ms-TPES assignments and address sampling effects, especially the temperature dependence of ms-TPES due to rovibrational broadening. Data acquisition approaches and the Stark shift from the extraction field are also considered to arrive at general recommendations. Finally, the PhotoElectron PhotoIon Spectral Compendium (https://pepisco.psi.ch), a spectral database hosted at Paul Scherrer Institute to support assignment, is introduced.

Tuning the zeolite acidity enables selectivity control by suppressing ketene formation in lignin catalytic pyrolysis.

Unveiling catalytic mechanisms at a molecular level aids rational catalyst design and selectivity control for process optimization. In this study, we find that the Brønsted acid site density of the zeolite catalyst efficiently controls the guaiacol catalytic pyrolysis mechanism. Guaiacol demethylation to catechol initiates the reaction, as evidenced by the detected methyl radicals. The mechanism branches to form either fulvenone (c-C5H4 = C = O), a reactive ketene intermediate, by catechol dehydration, or phenol by acid-catalyzed dehydroxylation. At high Brønsted acid site density, fulvenone formation is inhibited due to surface coordination configuration of its precursor, catechol. By quantifying reactive intermediates and products utilizing operando photoelectron photoion coincidence spectroscopy, we find evidence that ketene suppression is responsible for the fivefold phenol selectivity increase. Complementary fulvenone reaction pathway calculations, along with 29Si NMR-MAS spectroscopy results corroborate the mechanism. The proposed, flexible operando approach is applicable to a broad variety of heterogeneous catalytic reactions.

Comprehensive characterization of tumor microenvironment in colorectal cancer via molecular analysis.

Colorectal cancer (CRC) remains a challenging and deadly disease with high tumor microenvironment (TME) heterogeneity. Using an integrative multi-omics analysis and artificial intelligence-enabled spatial analysis of whole-slide images, we performed a comprehensive characterization of TME in colorectal cancer (CCCRC). CRC samples were classified into four CCCRC subtypes with distinct TME features, namely, C1 as the proliferative subtype with low immunogenicity; C2 as the immunosuppressed subtype with the terminally exhausted immune characteristics; C3 as the immune-excluded subtype with the distinct upregulation of stromal components and a lack of T cell infiltration in the tumor core; and C4 as the immunomodulatory subtype with the remarkable upregulation of anti-tumor immune components. The four CCCRC subtypes had distinct histopathologic and molecular characteristics, therapeutic efficacy, and prognosis. We found that the C1 subtype may be suitable for chemotherapy and cetuximab, the C2 subtype may benefit from a combination of chemotherapy and bevacizumab, the C3 subtype has increased sensitivity to the WNT pathway inhibitor WIKI4, and the C4 subtype is a potential candidate for immune checkpoint blockade treatment. Importantly, we established a simple gene classifier for accurate identification of each CCCRC subtype. Collectively our integrative analysis ultimately established a holistic framework to thoroughly dissect the TME of CRC, and the CCCRC classification system with high biological interpretability may contribute to biomarker discovery and future clinical trial design.

Infrared photodissociation spectroscopy of mass-selected [TaO3(CO2)n]+ (n = 2-5) complexes in the gas phase.

We report a joint experimental and theoretical study on the structures of gas-phase [TaO3(CO2)n]+ (n = 2-5) ion-molecule complexes. Infrared photodissociation spectra of mass-selected [TaO3(CO2)n]+ complexes were recorded in the frequency region from 2200 to 2450 cm-1 and assigned through comparing with the simulated infrared spectra of energetically low-lying structures derived from quantum chemical calculations. With the increasing number of attached CO2 molecules, the larger clusters show significantly enhanced fragmentation efficiency and a strong band appears at around 2350 cm-1 near the free CO2 antisymmetric stretching vibration band, indicating only a small perturbation of CO2 molecules on the secondary solvation sphere while higher frequency bands corresponding to the core structure remain largely unaffected. A core structure [TaO3(CO2)3]+ is identified to which subsequent CO2 ligands are weakly attached and the most favorable cluster growth path is verified to proceed on the triplet potential energy surface higher in energy than that of ground states. Theoretical exploration reveals a two-state reactivity (TSR) scenario in which the energetically favored triplet transition state crosses over the singlet ground state to form a TaO3+ core ion, providing new information on the cluster formation correlated with the reactivity of tantalum metal oxides towards CO2.

Ingenious Artificial Leaf Based on Covalent Organic Framework Membranes for Boosting CO2 Photoreduction.

Covalent organic frameworks (COFs) hold the potential in converting CO2 with water into value-added fuels and O2 to save the deteriorating ecological environment. However, reaching high yield and selectivity is a grand challenge under metal-, photosensitizer-, or sacrificial reagent-free conditions. Here, inspired by microstructures of natural leaves, we designed triazine-based COF membranes with the integration of steady light-harvesting sites, efficient catalytic center, and fast charge/mass transfer configuration to fabricate a novel artificial leaf for the first time. Significantly, a record high CO yield of 1240 µmol g-1 in a 4 h reaction, approximately 100% selectivity, and a long lifespan (at least 16 cycles) were achieved under gas-solid conditions without using any metal, photosensitizer, or sacrificial reagent. Unlike the existing knowledge, the chemical structural unit of triazine-imide-triazine and the unique physical form of the COF membrane are predominant for such a remarkable photocatalysis. This work opens a new pathway to simulating photosynthesis in leaves and may motivate relevant research in the future.

A direct liquid sampling interface for photoelectron photoion coincidence spectroscopy.

We introduce an effective and flexible high vacuum interface to probe the liquid phase with photoelectron photoion coincidence (liq-PEPICO) spectroscopy at the vacuum ultraviolet (VUV) beamline of the Swiss Light Source. The interface comprises a high-temperature sheath gas-driven vaporizer, which initially produces aerosols. The particles evaporate and form a molecular beam, which is skimmed and ionized by VUV radiation. The molecular beam is characterized using ion velocity map imaging, and the vaporization parameters of the liq-PEPICO source have been optimized to improve the detection sensitivity. Time-of-flight mass spectra and photoion mass-selected threshold photoelectron spectra (ms-TPES) were recorded for an ethanolic solution of 4-propylguaiacol, vanillin, and 4-hydroxybenzaldehyde (1 g/l of each). The ground state ms-TPES band of vanillin reproduces the reference, room-temperature spectrum well. The ms-TPES for 4-propylguaiacol and 4-hydroxybenzaldehyde are reported for the first time. Vertical ionization energies obtained by equation-of-motion calculations reproduce the photoelectron spectral features. We also investigated the aldol condensation dynamics of benzaldehyde with acetone using liq-PEPICO. Our direct sampling approach, thus, enables probing reactions at ambient pressure during classical synthesis procedures and microfluidic chip devices.

Unraveling Radical and Oxygenate Routes in the Oxidative Dehydrogenation of Propane over Boron Nitride.

Oxidative dehydrogenation of propane (ODHP) is an emerging technology to meet the global propylene demand with boron nitride (BN) catalysts likely to play a pivotal role. It is widely accepted that gas-phase chemistry plays a fundamental role in the BN-catalyzed ODHP. However, the mechanism remains elusive because short-lived intermediates are difficult to capture. We detect short-lived free radicals (CH3•, C3H5•) and reactive oxygenates, C2-4 ketenes and C2-3 enols, in ODHP over BN by operando synchrotron photoelectron photoion coincidence spectroscopy. In addition to a surface-catalyzed channel, we identify a gas-phase H-acceptor radical- and H-donor oxygenate-driven route, leading to olefin production. In this route, partially oxidized enols propagate into the gas phase, followed by dehydrogenation (and methylation) to form ketenes and finally yield olefins by decarbonylation. Quantum chemical calculations predict the >BO dangling site to be the source of free radicals in the process. More importantly, the easy desorption of oxygenates from the catalyst surface is key to prevent deep oxidation to CO2.

Isomer-Dependent Threshold Photoelectron Spectroscopy and Dissociative Photoionization Mechanism of Anisaldehyde.

We studied the threshold photoionization and dissociative ionization of para-, meta-, and ortho-anisaldehyde by photoelectron photoion coincidence spectroscopy in the 8.20-19.00 eV photon energy range. Vertical ionization energies by equation of motion-ionization potential-coupled cluster singles and doubles (EOM-IP-CCSD) calculations reproduce the photoelectron spectral features in all three isomers. The dissociative photoionization (DPI) pathways of para- and meta-anisaldehyde are similar and differ markedly from those of ortho-anisaldehyde. In the para and meta isomers, the lowest-energy DPI channel corresponds to hydrogen atom loss to form the C8H7O2+ fragment at m/z 135, which undergoes sequential dissociation processes at higher energies, such as carbon monoxide loss to C7H7O+ (m/z 107) and further, sequential CH3, CH2O, and CH2CO losses to produce C6H4O+ (m/z 92), C6H5+ (m/z 77), and C5H5+ (m/z 65), respectively. Carbon monoxide loss from the parent ions, yielding C7H8O+ (m/z 108), is a subordinate dissociation channel parallel to H atom loss. At higher energies, it also gives rise to sequential formaldehyde (CH2O) loss to produce C6H6+ (m/z 78). In the ortho-anisaldehyde cation, the vicinity of the aldehyde and methoxy groups opens up low-energy hydrogen-transfer processes, which allow for seven fragmentation channels to compete effectively with the H- and CO-loss channels. Thus, the fragmentation mechanism changes considerably, thanks to the steric interaction of the substituents. Functional group interactions, in particular H transfer pathways, must therefore be considered when predicting the isomer-specific unimolecular decomposition mechanism of cationic and neutral species, as well as mass spectra for isomers.

Solvating power regulation enabled low concentration electrolyte for lithium batteries.

Li+ solvation structures have a decisive influence on the electrode/electrolyte interfacial properties and battery performances. Reduced salt concentration may result in an organic rich solid electrolyte interface (SEI) and catastrophic cycle stability, which makes low concentration electrolytes (LCEs) rather challenging. Solvents with low solvating power bring in new chances to LCEs due to the weak salt-solvent interactions. Herein, an LCE with only 0.25 mol L-1 salt is prepared with fluoroethylene carbonate (FEC) and 1,1,2,2-tetrafluoroethyl-2,2,3,3-tetrafluoropropylether (D2). Molecular dynamics simulations and experiments prove that the low solvating power solvent FEC not only renders reduced desolvation energy to Li+ and improves the battery kinetics, but also promotes the formation of a LiF-rich SEI that hinders the electrolyte consumption. Li||Cu cell using the LCE shows a high coulombic efficiency of 99.20%, and LiNi0.6Co0.2Mn0.2O2||Li cell also exhibits satisfying capacity retention of 89.93% in 200 cycles, which demonstrates the great potential of solvating power regulation in LCEs development.

Ketenes in the Induction of the Methanol-to-Olefins Process.

Ketene (CH2 =C=O) has been postulated as a key intermediate for the first olefin production in the zeolite-catalyzed chemistry of methanol-to-olefins (MTO) and syngas-to-olefins (STO) processes. The reaction mechanism remains elusive, because the short-lived ethenone ketene and its derivatives are difficult to detect, which is further complicated by the low expected ketene concentration. We report on the experimental detection of methylketene (CH3 -CH=C=O) formed by the methylation of ketene on HZSM-5 via operando synchrotron photoelectron photoion coincidence (PEPICO) spectroscopy. Ketene is produced in situ from methyl acetate. The observation of methylketene as the ethylene precursor evidences a computationally predicted ketene-to-ethylene route proceeding via a methylketene intermediate followed by decarbonylation.

lncRNA DLEU1 Modulates Proliferation, Inflammation, and Extracellular Matrix Degradation of Chondrocytes through Regulating miR-671-5p.

Long noncoding RNAs (lncRNAs) have been shown to be involved in the development of osteoarthritis. However, the expression, function, and mechanism of DLEU1 in OA development remain largely unclear. The present reference demonstrates that DLEU1 is overexpressed in OA specimens compared to control cartilages. Inflammatory cytokines IL-1ß, TNF-α, and IL-6 induce DLEU1 expression in chondrocytes. Ectopic expression of DLEU1 induces chondrocyte proliferation, degradation of ECM, and inflammation mediators such as IL-6, IL-8, and TNF-α secretion. Moreover, we demonstrated that DLEU1 targets miR-671-5p expression in chondrocytes. Overexpression of DLEU1 suppresses miR-671-5p expression in chondrocytes. The expression of miR-671-5p is decreased in OA specimens compared to control cartilages. There is a negative correlation between the expression of miR-671-5p and DLEU1 in OA specimens. Inflammatory mediators IL-1ß, TNF-α, and IL-6 suppress miR-671-5p expression in OA specimens. Elevated expression of miR-671-5p suppresses chondrocyte proliferation, degradation of ECM, and secretion of inflammation mediators. DLEU1 overexpression promotes chondrocytes proliferation, degradation of ECM, and secretion of inflammation mediators via regulating miR-671-5p. These results suggested that DLEU1 acts as one destructive role in OA development via regulating miR-671-5p.

Continuous Pyrolysis Microreactors: Hot Sources with Little Cooling? New Insights Utilizing Cation Velocity Map Imaging and Threshold Photoelectron Spectroscopy.

Resistively heated silicon carbide microreactors are widely applied as continuous sources to selectively prepare elusive and reactive intermediates with astrochemical, catalytic, or combustion relevance to measure their photoelectron spectrum. These reactors also provide deep mechanistic insights into uni- and bimolecular chemistry. However, the sampling conditions and effects have not been fully characterized. We use cation velocity map imaging to measure the velocity distribution of the molecular beam signal and to quantify the scattered, rethermalized background sample. Although translational cooling is efficient in the adiabatic expansion from the reactor, the breakdown diagrams of methane and chlorobenzene confirm that the molecular beam component exhibits a rovibrational temperature comparable with that of the reactor. Thus, rovibrational cooling is practically absent in the expansion from the microreactor. The high rovibrational temperature also affects the threshold photoelectron spectrum of both benzene and the allyl radical in the molecular beam, but to different degrees. While the extreme broadening of the benzene TPES suggests a complex ionization mechanism, the allyl TPES is in fact consistent with an internal temperature close to that of the reactor. The background, room-temperature spectra of both are superbly reproduced by Franck-Condon simulations at 300 K. On the one hand, this leads us to suggest that room-temperature reference spectra should be used in species identification. On the other hand, analysis of the allyl iodide pyrolysis data shows that iodine atoms often recombine to form molecular iodine on the chamber surfaces. Such sampling effects may distort the chemical composition of the scattered background with respect to the molecular beam signal emanating directly from the reactor. This must be considered in quantitative analyses and kinetic modeling.

Synergistic Effect of TMSPi and FEC in Regulating the Electrode/Electrolyte Interfaces in Nickel-Rich Lithium Metal Batteries.

Nickel-rich LiNi0.8Co0.1Mn0.1O2 (NCM811) with respect to Li metal can enhance the energy density of lithium batteries effectively. However, the unstable Li deposition, together with the dissolution and migration of transition metal (TM) ions toward the anode deteriorate the cycle performance of NCM811||Li battery, especially when commercial carbonate electrolyte is used. Herein, tris(trimethylsilyl)phosphite (TMSPi) and fluoroethylene carbonate (FEC) are used to construct a dual-additive electrolyte, by which both electrodes can be protected. It is found that TMSPi can be preferentially adsorbed on the cathode surface through its strong coordination with Ni4+, playing the role as a HF scavenger and suppressing TM ions dissolution, as well as mitigating the structural degradation of the cathode effectively. When it comes to the lithium anode, the presence of TMSPi may lead to side reactions with Li metal, accompanied by fast dendrite growth. The introduction of FEC could facilitate the formation of stable electrode/electrolyte interfaces on both sides. Particularly, reduce the direct contact between TMSPi and Li anode, thus ameliorate the incompatibility issue. Consequently, the NCM811||Li cell with dual-additive demonstrates excellent capacity retention of 81.2% after 500 cycles at 1 C rate. As a sharp contrast, it only retains 13.9% in the one with blank electrolyte. The findings of this work provide a new insight into enhancing the cycle performance of NCM811||Li system via the synergistic effect between additives.

Identification and validation of a novel signature for prediction the prognosis and immunotherapy benefit in bladder cancer.

BACKGROUND: Bladder cancer (BC) is a common urinary tract system tumor with high recurrence rate and different populations show distinct response to immunotherapy. Novel biomarkers that can accurately predict prognosis and therapeutic responses are urgently needed. Here, we aim to identify a novel prognostic and therapeutic responses immune-related gene signature of BC through a comprehensive bioinformatics analysis. METHODS: The robust rank aggregation was conducted to integrate differently expressed genes (DEGs) in datasets of the Cancer Genome Atlas (TCGA) and the gene expression omnibus (GEO). Lasso and Cox regression analyses were performed to formulate a novel mRNA signature that could predict prognosis of BC patients. Subsequently, the prognostic value and predictive value of the signature was validated with two independent cohorts GSE13507 and IMvigor210. Finally, quantitative Real-time PCR (qRT-PCR) analysis was conducted to determine the expression of mRNAs in BC cell lines (UM-UC-3, EJ-1, SW780 and T24). RESULTS: We built a signature comprised the eight mRNAs: CNKSR1, COPZ2, CXorf57, FASN, PCOLCE2, RGS1, SPINT1 and TPST1. Our prognostic signature could be used to stratify BC population into two risk groups with distinct immune profile and responsiveness to immunotherapy. The results of qRT-PCR demonstrated that the eight mRNAs exhibited different expression levels in BC cell lines. CONCLUSION: Our study constructed a convenient and reliable 8-mRNA gene signature, which might provide prognostic prediction and aid treatment decision making of BC patients in clinical practice.

A plethora of isomerization processes and hydrogen scrambling in the fragmentation of the methanol dimer cation: a PEPICO study.

The valence photoionization of light and deuterated methanol dimers was studied by imaging photoelectron photoion coincidence spectroscopy in the 10.00-10.35 eV photon energy range. Methanol clusters were generated in a rich methanol beam in nitrogen after expansion into vacuum. They generally photoionize dissociatively to protonated methanol cluster cations, (CH3OH)nH+. However, the stable dimer parent ion (CH3OH)2+ is readily detected below the dissociation threshold to yield the dominant CH3OH2+ fragment ion. In addition to protonated methanol, we could also detect the water- and methyl-loss fragment ions of the methanol dimer cation for the first time. These newly revealed fragmentation channels are slow and cannot compete with protonated methanol cation formation at higher internal energies. In fact, the water- and methyl-loss fragment ions appear together and disappear at a ca. 150 meV higher energy in the breakdown diagram. Experiments with selectively deuterated methanol samples showed H scrambling involving two hydroxyl and one methyl hydrogens prior to protonated methanol formation. These insights guided the potential energy surface exploration to rationalize the dissociative photoionization mechanism. The potential energy surface was further validated by a statistical model including isotope effects to fit the experiment for the light and the perdeuterated methanol dimers simultaneously. The (CH3OH)2+ parent ion dissociates via five parallel channels at low internal energies. The loss of both CH2OH and CH3O neutral fragments leads to protonated methanol. However, the latter, direct dissociation channel is energetically forbidden at low energies. Instead, an isomerization transition state is followed by proton transfer from a methyl group, which leads to the CH3(H)OH+⋯CH2OH ion, the precursor to the CH2OH-, H2O-, and CH3-loss fragments after further isomerization steps, in part by a roaming mechanism. Water loss yields the ethanol cation, and two paths are proposed to account for m/z 49 fragment ions after CH3 loss. The roaming pathways are quickly outcompeted by hydrogen bond breaking to yield CH3OH2+, which explains the dominance of the protonated methanol fragment ion in the mass spectrum.