Validation of endoplasmic reticulum stress-related gene signature to predict prognosis and immune landscape of patients with non-small cell lung cancer.

BACKGROUND: Lung cancer is one of the most common cancers worldwide, with the incidence increasing each year. It is crucial to improve the prognosis of patients who have lung cancer. Non-Small Cell Lung Cancer (NSCLC) accounts for the majority of lung cancer. Though its prognostic significance in NSCLC has not been often documented, Endoplasmic Reticulum (ER) stress has been identified to be implicated in tumour malignant behaviours and resistance to treatment. OBJECTIVE: This work aimed to develop a gene profile linked to ER stress that could be applied to predictive and risk assessment for non-small cell lung cancer. METHODS: Data from 1014 NSCLC patients were sourced from The Cancer Genome Atlas (TCGA) database, integrating clinical and Ribonucleic Acid (RNA) information. Diverse analytical techniques were utilized to identify ERS-associated genes associated with patients' prognoses. These techniques included Kaplan-Meier analysis, univariate Cox regression, Least Absolute Shrinkage and Selection Operator regression analysis (LASSO) regression, and Pearson correlation analysis. Using a risk score model obtained from multivariate Cox analysis, a nomogram was created and validated to classify patients into high- and low-risk groups. The study employed the CIBERSORT algorithm and Single-Sample Gene Set Eenrichment Analysis (ssGSEA) to investigate the tumour immune microenvironment. We used the Genomics of Drug Sensitivity in Cancer (GDSC) database and R tools to identify medicines that could be responsive. RESULTS: Four genes - FABP5, C5AR1, CTSL, and LTA4H - were chosen to create the risk model. Overall Survival (OS) was considerably lower (P< 0.05) in the high-risk group. When it came to predictive accuracy, the risk model outperformed clinical considerations. Several medication types that are sensitive to high-risk groups were chosen. CONCLUSION: Our study has produced a gene signature associated with ER stress that may be employed to forecast the prognosis and therapeutic response of non-small cell lung cancer patients.

Cost-Utility Analysis of Berberine Chemoprevention for Colorectal Cancer After Polypectomy.

Background Chemoprevention, such as berberine, has been developed as an alternative or complementary strategy to colonoscopy surveillance and has shown promise in reducing the morbidity and mortality of colorectal cancer. This study aims to evaluate the cost-effectiveness of berberine for postpolypectomy patients from the US third-party payer. Methods A Markov microsimulation model was developed to compare the cost and efficacy of berberine to no intervention, colonoscopy, and the combination of berberine and colonoscopy in postpolypectomy patients. Results After simulating 1 million patients, the study found that colonoscopy alone had a mean cost of $16,391 and mean quality-adjusted life-years (QALYs) of 16.03 per patient, whereas adding berberine slightly reduced the mean cost to $15,609 with a mean QALY of 16.05, making it a dominant strategy. Berberine therapy alone was less effective than colonoscopy alone, with a higher mean cost of $37,480 and a mean QALY of 15.32 per patient. However, berberine therapy was found to be a dominant strategy over no intervention. Conclusions Adding berberine to colonoscopy is the most cost-saving and effective approach for postpolypectomy patients. For patients who refuse or have limited access to colonoscopy, berberine alone is likely to be a dominant strategy compared to no intervention.

Built-in electric field in NiO-CuO heterostructures to regulate the hydroxide adsorption sites for 5-hydroxymethylfurfural electrooxidation assisted hydrogen production.

The development of catalysts with suitable adsorption behavior for the reaction molecules and the elucidation of their internal structure-adsorption-catalytic activity relationships are crucial for the electrooxidation of 5-hydroxymethylfurfural (HMF). In this work, NiO-CuO heterostructures with a spontaneous built-in electric field (BEF) are specifically designed and used to regulate the OH- adsorption site for freeing up the active site of HMF for the HMF oxidation reaction (HMFOR). The mechanism driving electron pumping/accumulation of the BEF is examined by X-ray photoelectron spectroscopy (XPS) and ultraviolet photoelectron spectroscopy (UPS). Electrochemical data and theoretical calculations show that BEF modulates the adsorption energy and adsorption site of substrate molecules, thereby enhancing the performance of HMFOR and hydrogen evolution reaction (HER). Notably, the NiO-CuO electrode demonstrates high 2,5-Furandicarboxylic acid (FDCA) selectivity (99.76 %) and generation rate (13.79 mmol gcat-1 h-1). It only requires 1.33 V to obtain a current density of 10 mA cm-2 for HMFOR-coupled H2 evolution. This research introduces a novel approach by regulating the adsorption of reactive molecules for HMFOR-assisted H2 evolution.

Preparation and Characterization of Bismaleimide-Resin-Based Composite Materials.

This study utilized bismaleimide (BMI) resin, reinforced with introduced ether bonds, as a binding matrix, in combination with silicon carbide (SiC), for the fabrication of composite materials. A thorough investigation was conducted to assess the influence of diverse processing parameters on the mechanical properties and high-temperature thermo-oxidative stability of these composites. Experimental results indicate a notable improvement in the mechanical properties of the composites upon the incorporation of ether bonds, in contrast to their unmodified counterparts. The variation in performance among composites with different ratios and molding densities is apparent. Within a certain range, an increase in resin content and molding density is correlated with improved bending strength in the composites. With a resin content of 27.5 vol% and a molding density of 2.31 g/cm3, the composite achieved a maximum flexural strength of 109.52 MPa, representing a 24% increase compared to its pre-modification state. Even after exposure to high-temperature heat treatment, the composites displayed commendable mechanical properties compared to their pre-ether bond modification counterparts, maintaining 74.5% of the strength of the untreated composites at 300 °C. The scanning electron microscopy (SEM) microstructures of composite materials correlate remarkably well with their mechanical properties.

Research on Sol-Gel Synthesis of Low-Temperature Na2O-B2O3-SiO2 Vitrified Bonds and Preparation of High-Strength Stacked Abrasives Using the Molding and Crushing Method.

Currently, the sol-gel technique is employed in the synthesis of high-performance vitrified bonds; however, its application in the fabrication of stacked abrasives has been minimally explored. Furthermore, the methods utilized in the production of abrasive particles for stacked abrasives are technically challenging and incur high costs, which hinders their actual industrial application. Consequently, this study utilizes the sol-gel approach to synthesize a Na2O-B2O3-SiO2 ternary system vitrified bond powder and employs a molding and crushing method, which offers a lower technological barrier and reduced preparation costs, for the production of abrasive particles subsequently fabricating corundum stacked abrasives. Upon setting the binder composition to a molar ratio of n(SiO2):n(B2O3):n(Na2O) = 65:23:12, it was observed that the crystallization within the glass matrix was minimized and the optimal sintering temperature for the synthesized laminate abrasive to be sustained at 820 °C. At the aforementioned temperature, the binder melt is capable of flowing uniformly amongst the abrasive granules, thereby ensuring a robust encapsulation of the particles. The average single particle compressive strength of the prepared corundum stacked abrasive with a grain size of forty mesh can reach the highest of all composition points at 28.56 N and the average single particle compressive strength of the prepared diamond stacked abrasive is 28.14 N.

Rim-Based Binding of Perfluorinated Acids to Pillararenes Purifies Water.

Per- and polyfluoroalkyl substances (PFAS) pose a rapidly increasing global problem as their widespread use and high stability lead worldwide to water contamination, with significant detrimental health effects.[1] Supramolecular chemistry has been invoked to develop materials geared towards the specific capture of PFAS from water,[2] to reduce the concentration below advisory safety limits (e.g., 70 ng/L for the sum of perfluorooctane sulfonic acid, PFOS and perfluorooctanoic acid, PFOA). Scale-up and use in natural waters with high PFAS concentrations has hitherto posed a problem. Here we report a new type of host-guest interaction between deca-ammonium-functionalized pillar[5]arenes (DAF-P5s) and perfluoroalkyl acids. DAF-P5 complexes show an unprecedented 1 : 10 stoichiometry, as confirmed by isothermal calorimetry and X-ray crystallographic studies, and high binding constants (up to 106 M-1) to various polyfluoroalkyl acids. In addition, non-fluorinated acids do not hamper this process significantly. Immobilization of DAF-P5s allows a simple single-time filtration of PFAS-contaminated water to reduce the PFOS/PFOA concentration 106 times to 15-50 ng/L level. The effective and fast (<5 min) orthogonal binding to organic molecules without involvement of fluorinated supramolecular hosts, high breakthrough capacity (90 mg/g), and robust performance (>10 regeneration cycles without decrease in performance) set a new benchmark in PFAS-absorbing materials.

Tunable Supramolecular Ag+-Host Interactions in Pillar[n]arene[m]quinones and Ensuing Specific Binding to 1-Alkynes.

We developed an improved, robust synthesis of a series of pillar[6]arenes with a varying number (0-3) of quinone moieties in the ring. This easy-to-control variation yielded a gradually less electron-rich cavity in going from zero to three quinone units, as shown from the strength of host-guest interactions with silver ions. Such macrocycle-Ag2 complexes themselves were shown to display an unprecedented, sharp distinction between terminal alkynes, which strongly bound to such complexes, and internal alkynes, internal alkenes and terminal alkenes, which do hardly bind.

Synthesis of Large Macrocycles with Chiral Sulfur Centers via Enantiospecific SuFEx and SuPhenEx Click Reactions.

Here we report the first asymmetric synthesis of large chiral macrocycles with chiral sulfur atoms. Building on stereospecific SuFEx and SuPhenEx click chemistries, this approach utilizes disulfonimidoyl fluorides and disulfonimidoyl p-nitrophenolates─which are efficient building blocks with two chiral sulfur centers, and diphenols to efficiently form novel S-O bonds. Characteristic results include the enantiospecific one-step synthesis of rings consisting of 21-58 members and characterization of both enantiomers (R,R and S,S) by e.g. X-ray crystallography.

Development of a monoclonal antibody recognizing novel linear neutralizing epitope on H protein of canine distemper virus vaccine strains (America-1 genotype).

Canine distemper virus (CDV) is an economically important virus responsible for canine distemper (CD), a highly contagious disease that afflicts various animal species worldwide. The hemagglutinin (H) protein is the major neutralizing target of virus. Therefore, it is often considered as immunogen to prepare neutralizing antibodies. The accurate identification of neutralizing epitope will provide important antigenic information and extend the knowledge of mechanisms of virus neutralization. In this study, we generated a neutralizing monoclonal antibody (mAb) 4C6 against CDV H protein, and defined the minimal linear epitope 238DIEREFDT245, which was highly conserved in America-1 genotype of CDV strains (vaccines). The mAb 4C6 could not react with a CDV strain that had two substitutions of D238Y and R241G in the epitope, which appeared in most CDV strains of the other genotypes. Besides, a few different amino acid mutations in the epitope were also included. Collectively, the epitope 238DIEREFDT245 was variable in the other genotypes of CDV strains. The epitope 238DIEREFDT245 was exposed to the surface of CDV H protein, showing good antigenicity. These data will provide insights into structure, function and antigenicity of H protein and lay the foundation for the development of diagnostic technologies and vaccine design for CDV.

Preparation and Characterization of Carbide Particle-Toughened Si-B System of High Thermostability Polycrystalline Diamond by HPHT Sintering.

In this research, we report the synthesis of Si-TmC-B/PCD composites using Si, B, and transition metal carbide particles (TmC) as binders at high pressure and high temperature (HPHT method, 5.5 GPa and 1450 °C). The microstructure, elemental distribution, phase composition, thermal stability, and mechanical properties of PCD composites were systematically investigated. The Si-B/PCD sample is thermally stable in air at 919 °C. The initial oxidation temperature of the PCD sample with ZrC particles is as high as 976 °C, and it also has a maximum flexural strength of 762.2 MPa, and the highest fracture toughness of 8.0 MPa·m1/2.