Correlation between IL3 signaling pathway-related genes and immune checkpoint inhibitor efficacy in patients with renal cell carcinoma.

BACKGROUND: There is a lack of effective biomarkers that predict immunotherapy efficacy in clear cell renal cell carcinoma(KIRC). OBJECTIVE: We aimed to identify biomarkers that would predict the efficacy of KIRC treatment with immune checkpoint inhibitors (ICIs). METHODS: Cohort data of KIRC patients with somatic mutations, mRNA expression and survival data from The Cancer Genome Atlas (TCGA) database and immunotherapy cohort and Genomics of Drug Sensitivity in Cancer (GDSC) database were analyzed and divided into interleukin 3 (IL3) pathway-related genes high expression (IL3-High) and IL3 pathway-related genes low expression (IL3-Low) groups according to pathway expression status to assess the relationship between the IL3 pathway-related genes activation status and the prognosis of KIRC patients treated with ICIs. The data were validated by immunohistochemistry experiments, and possible mechanisms of action were explored at the level of gene mutation landscape, immune microenvironment characteristics, transcriptome and copy number variation(CNV) characteristicsRESULTS: The IL3 pathway-related genes was an independent predictor of the efficacy of ICIs in KIRC patients, and the IL3-High group had a longer overall survival (OS); KIRC patients in the IL3-High group had increased levels of chemokines, cytolysis, immune checkpoint gene expression and abundant immunity. The IL3-Low group had poor immune cell infiltration and significant downregulation of complement activation, cytophagy, B-cell activation, and humoral immune response pathways. The high group was more sensitive to targeted drugs of some signaling pathways, and its efficacy in combining these drugs with immunity has been predicted in the published literature. CONCLUSION: The IL3 pathway-related genes can be used as a predictor of the efficacy of ICIs in KIRC. The IL3 pathway-related genes may affect the therapeutic efficacy of ICIs by affecting the expression of immune-related molecules, immune cell infiltration, and the level of immune response pathways.

CACNA1C mutation as a prognosis predictor of immune checkpoint inhibitor in skin cutaneous melanoma.

Aims: There is an urgent need for appropriate biomarkers that can precisely and reliably predict immunotherapy efficacy, as immunotherapy responses can differ in skin cutaneous melanoma (SKCM) patients. Methods: In this study, univariate regression models and survival analysis were used to examine the link between calcium voltage-gated channel subunit alpha 1C (CACNA1C) mutation status and immunotherapy outcome in SKCM patients receiving immunotherapy. Mutational landscape, immunogenicity, tumor microenvironment and pathway-enrichment analyses were also performed. Results: The CACNA1C mutation group had a better prognosis, higher immunogenicity, lower endothelial cell infiltration, significant enrichment of antitumor immune response pathways and significant downregulation of protumor pathways. Conclusion: CACNA1C mutation status is anticipated to be a biomarker for predicting melanoma immunotherapy effectiveness.

Aims: The treatment to make the immune system work better is also used to treat a skin cancer called skin cutaneous melanoma (SKCM). We need new ways to predict if the treatment will work. Methods: We looked at two groups of people getting the treatment to make the immune system work better. One group had a special change in their bodies, and the other group did not. We looked at how this change affected the patients. We also looked at how to make their immune system stronger. Results: We found that people with mutations tend to have better chances of getting better from their sickness. Conclusion: We think that this might be a good way to tell if immunotherapy will work well for this type of SKCM.

Structural characteristics, functional properties, antioxidant and hypoglycemic activities of pectins from feijoa (Acca sellowiana) peel.

The structure characteristics, functional properties, antioxidant and hypoglycemic activities of pectins extracted from feijoa peel with water (FP-W), acid (FP-A) and alkali (FP-B) were investigated. Results showed that the feijoa peel pectins (FPs) were mainly composed of galacturonic acid, arabinose, galactose and rhamnose. FP-W and FP-A had higher proportion of homogalacturonan domain, degree of esterification and molecular weight (for main component) than FP-B; FP-B owned the highest yield, protein and polyphenol contents. FP-W had a compact and smooth surface morphology unlike FP-A and FP-B. FP-W and FP-A had better thermal stability than FP-B. The rheological analysis suggested that the FPs exhibited pseudoplastic fluid behavior, and the elastic characteristics were dominant. Results showed that FP-W and FP-B had superior antioxidant and hypoglycemic activities than FP-A. According to correlation analysis, monosaccharide composition, sugar ratios and degree of acetylation were chief factors affecting the functional properties, antioxidant and hypoglycemic activities of the FPs.

Determination of Biogenic Amines in Wine from Chinese Markets Using Ion Chromatography-Tandem Mass Spectrometry.

A method for the determination of nine biogenic amines (BAs) in wine was established using ion chromatography-tandem mass spectrometry (IC-MS/MS) without derivatization. BAs were separated by a cation exchange column (IonPac CG17, 50 mm × 4 mm, 7 µm) with a gradient aqueous formic acid elution. Good linearity was obtained for nine BAs with coefficients of determination (R2) > 0.9972 within the range of 0.01-50 mg/L. The limits of detection and quantification were within the ranges of 0.6-40 µg/L and 2.0-135 µg/L, respectively, with the exception of spermine (SPM). The recoveries were demonstrated within the range of 82.6-103.0%, with relative standard deviations (RSDs) of less than 4.2%. This simple method featuring excellent sensitivity and selectivity was suitable for the quantification of BAs in wines. The occurrence of BAs in 236 wine samples that are commercially available in China was determined. The BA levels in wines of different geographical origins varied significantly. The acute dietary exposure assessment of BAs was carried out by calculating the estimated short-term intake (ESTI) and comparing the acute reference dose (ARfD) specified by the European Food Safety Authority (EFSA). Results showed that the exposure to histamine (HIS) and tyramine (TYR) via the consumption of wines was much lower than the recommended ARfD level for healthy individuals. However, exposure could lead to symptoms in susceptible individuals. These results provided basic data regarding the occurrence and risk of BAs in wines for wine production, health guidance and consumer safety.

Mutations Status of NOTCH Signaling Pathway Predict Prognosis of Immune Checkpoint Inhibitors in Colorectal Cancer.

Purpose: In recent years, tumour immunotherapy has ushered in a new era of oncology treatment. However, the use of immune checkpoint inhibitors (ICIs) in the treatment of CRC remains limited. There is an urgent clinical need for precise biomarkers that can aid in the screening and treatment of CRC subtypes. Therefore, we focused on the NOTCH pathway mutation status and conducted a systematic analysis for its predictive value of ICI therapy efficacy. Methods: We collected mutational and clinical data from cohorts of CRC patients treated with ICIs. The relationship between NOTCH pathway mutations (NOTCH-MT) and CRC immunotherapy prognosis was analysed using univariate and multivariate Cox regression models. CRC cohort data from The Cancer Genome Atlas (TCGA) database were combined to obtain a comprehensive overview of immunogenicity and tumour microenvironment (TME) differences among different NOTCH pathway mutation statuses. Results: We observed greater infiltration of M1 macrophages, CD8+ T cells, neutrophils, and activated natural killer (NK) cells with NOTCH-MT status. Immunogenicity was also significantly higher in patients with NOTCH-MT, as were tumour mutational burden (TMB), neoantigen load (NAL), and the number of mutations in DNA damage repair (DDR) pathways. Conclusion: NOTCH-MT status was strongly associated with the prognosis of CRC patients treated with ICIs and is expected to serve as a novel biomarker and therapeutic target for CRC.

Nanocarbon-based catalysts for selective nitroaromatic hydrogenation: A mini review.

Selective hydrogenation of nitroaromatics to the corresponding anilines is a key topic for research in fine chemical industrial fields. Nanocarbon materials with good chemical stability, high electrical conductivity, and good mechanical performance have been regarded as promising candidates in the catalytic field, and have shown a wide range of applications in recent years. Controllable synthesis on the structure, morphology, and active sites of nanocarbon-based catalysts is vital to the development of highly efficient catalysts. In this mini-review, we summarize the recent progresses of nanocarbon materials by focusing on the synthesis approaches and their corresponding nanostructures, including carbon nanofibers, carbon nanotubes, graphene, porous carbon, carbon spheres, and metal organic framework-derived carbon materials. The design and catalytic performance of these nanocarbon materials have been systematically discussed. Finally, the emerging challenges and future prospective for developing advanced nanocarbon-based catalysts are outlined.

Chemical structure and antioxidant activity of a neutral polysaccharide from Asteris Radix et Rhizoma.

Asteris Radix et Rhizoma (AR) has been widely used as a herbal medicine for treating various symptoms and possesses a number of bioactivities. A neutral polysaccharide ARP-1 was isolated from AR with weight-average molecular weight of 214 kDa. The heteropolysaccharide ARP-1 was composed of fucose, arabinose, galactose, glucose and mannose with a molar ratio of 0.40:14.25:10.22:1.06:0.41. Linkage and NMR analysis showed that ARP-1 had a backbone containing →3,6)-ß-d-Galp-(1→ and →6)-ß-d-Galp-(1 â†’ residues, and oligosaccharide side chains containing Araf and Galp units were attached to the backbone at C-3 of →3,6)-ß-d-Galp-(1 â†’ residues. Antioxidant activity assays showed that ARP-1 exhibited potent antioxidant activities, including ABTS, hydroxy and DPPH radicals scavenging and reducing power. Besides, ARP-1 decreased the production of ROS and MDA, and improved the activities of SOD, which resulted in the protection of PC12 cells against H2O2-induced oxidative stress. The findings indicated that ARP-1 might be used as a potential natural antioxidant.

High-yield and sustainable synthesis of quinoidal compounds assisted by keto-enol tautomerism.

The classical synthesis of quinoids, which involves Takahashi coupling and subsequent oxidation, often gives only low to medium yields. Herein, we disclose the keto-enol-tautomerism-assisted spontaneous air oxidation of the coupling products to quinoids. This allows for the synthesis of various indandione-terminated quinoids in high isolated yields (85-95%). The origin of the high yield and the mechanism of the spontaneous air oxidation were ascertained by experiments and theoretical calculations. All the quinoidal compounds displayed unipolar n-type transport behavior, and single crystal field-effect transistors based on the micro-wires of a representative quinoid delivered an electron mobility of up to 0.53 cm2 V-1 s-1, showing the potential of this type of quinoid as an organic semiconductor.

Bandgap Engineering of an Aryl-Fused Tetrathianaphthalene for Visible-Blind Organic Field-Effect Transistors.

Stability problem of organic semiconductors (OSCs) because of photoabsorption has become a major barrier to large scale applications in organic field-effect transistors (OFETs). It is imperative to design OSCs which are insensitive to visible and near-infrared (VNIR) light to obtain both environmental and operational stability. Herein, taking a 2,3,8,9-tetramethoxy [1,4]benzodithiino[2,3-b][1,4]benzodithiine (TTN2) as an example, we show that controlling molecular configuration is an effective strategy to tune the bandgaps of OSCs for visible-blind OFETs. TTN2 adopts an armchair-like configuration, which is different from the prevailing planar structure of common OSCs. Because of the large bandgap, TTN2 exhibits no photoabsorption in the VNIR region and OFETs based on TTN2 show high environmental stability. The devices worked well after being stored in ambient air, (i.e. in the presence of oxygen and water) and light for over two years. Moreover, the OFETs show no observable response to light irradiation from 405-1,020 nm, which is also favorable for high operational stability.

Ultra-thin two-dimensional molecular crystals grown on a liquid surface for high-performance phototransistors.

A novel strategy for the growth of molecularly thin two-dimensional molecular crystals (2DMCs) of organic semiconductors with poor solubility was developed. Large-area bilayer 2DMCs were grown on a liquid surface at elevated temperatures, with record mobility and superior photoresponse.

Layer-Defining Strategy to Grow Two-Dimensional Molecular Crystals on a Liquid Surface down to the Monolayer Limit.

Two-dimensional molecular crystals (2DMCs) open a new door for the controllable growth of 2D materials by molecular design with a energy gap and solution processability. However, the growth of 2DMCs with defined molecular layers remains full of challenges. Herein, we report a novel method to produce various 2DMCs with a defined number of molecular layers. When the surface tension and viscosity are tuned to control the spreading of the solution on the liquid surface, large-area quasi-freestanding 2DMCs from bulk size down to the monolayer limit are obtained, which makes it possible to probe the intrinsic layer-dependent optoelectronic properties of organic semiconductors down to the physical limit, and paves the way for the application of 2DMCs in new optoelectronic devices and technologies.

A "Phase Separation" Molecular Design Strategy Towards Large-Area 2D Molecular Crystals.

2D molecular crystals (2DMCs) have attracted considerable attention because of their unique optoelectronic properties and potential applications. Taking advantage of the solution processability of organic semiconductors, solution self-assembly is considered an effective way to grow large-area 2DMCs. However, this route is largely blocked because a precise molecular design towards 2DMCs is missing and little is known about the relationship between 2D solution self-assembly and molecular structure. A "phase separation" molecular design strategy towards 2DMCs is proposed and layer-by-layer growth of millimeter-sized monolayer or few-layer 2DMCs is realized. High-performance organic phototransistors are constructed based on the 2DMCs with unprecedented photosensitivity (2.58 × 107 ), high responsivity (1.91 × 104 A W-1 ), and high detectivity (4.93 × 1015 Jones). This "phase separation" molecular design strategy provides a guide for the design and synthesis of novel organic semiconductors that self-assemble into large-area 2DMCs for advanced organic (opto)electronics.

2D Molecular Crystal Bilayer p-n Junctions: A General Route toward High-Performance and Well-Balanced Ambipolar Organic Field-Effect Transistors.

Ambipolar organic field-effect transistors (OFETs) are vital for the construction of high-performance all-organic digital circuits. The bilayer p-n junction structure, which is composed of separate layers of p- and n-type organic semiconductors, is considered a promising way to realize well-balanced ambipolar charge transport. However, this approach suffers from severely reduced mobility due to the rough interface between the polycrystalline thin films of p- and n-type organic semiconductors. Herein, 2D molecular crystal (2DMC) bilayer p-n junctions are proposed to construct high-performance and well-balanced ambipolar OFETs. The molecular-scale thickness of the 2DMC ensures high injection efficiency and the atomically flat surface of the 2DMC leads to high-quality p- and n-layer interfaces. Moreover, by controlling the layer numbers of the p- and n-type 2DMCs, the electron and hole mobilities are tuned and well-balanced ambipolar transport is accomplished. The hole and electron mobilities reach up to 0.87 and 0.82 cm2 V-1 s-1 , respectively, which are the highest values among organic single-crystalline double-channel OFETs measured in ambient air. This work provides a general route to construct high-performance and well-balanced ambipolar OFETs based on available unipolar materials.

Empirical Analysis and Modeling of Stop-Line Crossing Time and Speed at Signalized Intersections.

In China, a flashing green (FG) indication of 3 s followed by a yellow (Y) indication of 3 s is commonly applied to end the green phase at signalized intersections. Stop-line crossing behavior of drivers during such a phase transition period significantly influences safety performance of signalized intersections. The objective of this study is thus to empirically analyze and model drivers' stop-line crossing time and speed in response to the specific phase transition period of FG and Y. High-resolution trajectories for 1465 vehicles were collected at three rural high-speed intersections with a speed limit of 80 km/h and two urban intersections with a speed limit of 50 km/h in Shanghai. With the vehicle trajectory data, statistical analyses were performed to look into the general characteristics of stop-line crossing time and speed at the two types of intersections. A multinomial logit model and a multiple linear regression model were then developed to predict the stop-line crossing patterns and speeds respectively. It was found that the percentage of stop-line crossings during the Y interval is remarkably higher and the stop-line crossing time is approximately 0.7 s longer at the urban intersections, as compared with the rural intersections. In addition, approaching speed and distance to the stop-line at the onset of FG as well as area type significantly affect the percentages of stop-line crossings during the FG and Y intervals. Vehicle type and stop-line crossing pattern were found to significantly influence the stop-line crossing speed, in addition to the above factors. The red-light-running seems to occur more frequently at the large intersections with a long cycle length.