A systematic analysis of the global and regional burden of colon and rectum cancer and the difference between early- and late-onset CRC from 1990 to 2019.

The burden of colorectal cancer (CRC) varies substantially across different geographical locations. However, there was no further quantitative analysis of regional social development and the disease burden of CRC. In addition, the incidence of early- and late-onset CRC has increased rapidly in developed and developing regions. The main purpose of this study was to investigate the trends in CRC burden across different regions, in addition to the epidemiological differences between early and late-onset CRC and their risk factors. In this study, estimated annual percentage change (EAPC) was employed to quantify trends in age-standardized incidence rate (ASIR), mortality rate, and disability-adjusted life-years. Restricted cubic spline models were fitted to quantitatively analyze the relationship between trends in ASIR and Human Development Index (HDI). In addition, the epidemiological characteristics of early- and late-onset CRC were investigated using analyses stratified by age groups and regions. Specifically, meat consumption and antibiotic use were included to explore the differences in the risk factors for early- and late-onset CRC. The quantitative analysis showed that the ASIR of CRC was exponentially and positively correlated with the 2019 HDI in different regions. In addition, the growing trend of ASIR in recent years varied substantially across HDI regions. Specifically, the ASIR of CRC showed a significant increase in developing countries, while it remained stable or decreased in developed countries. Moreover, a linear correlation was found between the ASIR of CRC and meat consumption in different regions, especially in developing countries. Furthermore, a similar correlation was found between the ASIR and antibiotic use in all age groups, with different correlation coefficients for early-onset and late-onset CRC. It is worth mentioning that the early onset of CRC could be attributable to the unrestrained use of antibiotics among young people in developed countries. In summary, for better prevention and control of CRC, governments should pay attention to advocate self-testing and hospital visits among all age groups, especially among young people at high risk of CRC, and strictly control meat consumption and the usage of antibiotics.

The modulation relationship of genomic pattern of intratumor heterogeneity and immunity microenvironment heterogeneity in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world, with the second highest mortality rate among all cancer types. Growing evidence has demonstrated the notable effects of intratumor heterogeneity (ITH) and tumor immune microenvironment heterogeneity (TIMH) on the biological processes involved in HCC. However, the interactive mechanisms between ITH and TIMH is still unclear. The present study systematically screened the mRNA expression, simple nucleotide variation data and clinical data of samples from The Cancer Genome Atlas (TCGA). The mutant-allele tumor heterogeneity (MATH) score was used to represent ITH, and TCGA cohort was divided into two groups according to the MATH score. Next, different immune-related signaling pathways and enriched immune-related genes were identified using Gene Set Enrichment Analysis of these two groups, and the results revealed that interleukin-1α (IL1A) and serine/threonine-protein kinase PAK4 were associated with prognosis. Furthermore, CIBERSORT was utilized to calculate the fractions of 22 types of leukocytes to represent TIMH, and the fractions of M1 and M2 macrophages were confirmed to be associated with prognosis. Therefore, PAK4, interleukin-1α (IL1A), and M1/M2 ratio were selected as the key factors involved in the interaction between ITH and TIMH. Afterwards, microRNAs (miRNAs) that were linearly related to the M1/M2 ratio and the potential target genes of the miRNAs were screened. Finally, the regulatory network between PAK4, IL1A, and the M1/M2 ratio was established, bridged by the above miRNAs and the target genes. In addition, PAK4, heat shock protein 105 kDa and miRNA-1911 were demonstrated to be a key factor involved in immune response via Weighted Correlation Network Analysis in HCC.

Simultaneous photoelectrochemical and visualized immunoassay of ß-human chorionic gonadotrophin.

Herein, on the basis of the alkaline phosphate (ALP) induced reaction, a simultaneous photoelectrochemical (PEC) and visualized immunoassay has been established for the detection of ß-human chorionic gonadotrophin (ß-HCG). Specifically, in the proposed system, ALP stimulated the oxidative hydrolyzing transformation of 5-bromo-4-chloro-3-indoyl phosphate (BCIP) to an indigo precipitation, generating an insulating layer that impeded the interfacial mass and electron transfer and thus the photocurrent production. Meanwhile, a visualized detection could be performed according to the change of color intensity. Upon proper experimental conditions, the protocol possessed a detection range of 0.5-1000IU/L with a detection limit of (0.20±0.011)IU/L toward ß-HCG. With high sensitivity and specificity, this work presents the first general protocol for simultaneous PEC and visualized detection, which could be easily extended to addressing numerous other targets.

Invoking Direct Exciton-Plasmon Interactions by Catalytic Ag Deposition on Au Nanoparticles: Photoelectrochemical Bioanalysis with High Efficiency.

In this work, direct exciton-plasmon interactions (EPI) between CdS quantum dots (QDs) and Ag nanoparticles (NPs) were invoked ingeniously by catalytic Ag deposition on Au NPs for the stimulation of high efficient damping effect toward the excitonic responses in CdS QDs, on the basis of which a novel photoelectrochemical (PEC) bioanalytical format was achieved for sensitive microRNA detection. Specifically, upon the configurational change from the hairpin probe DNA to the "Y"-shaped ternary conjugate consisting of the original probe DNA, assistant DNA, and the target microRNA, the alkaline phosphatase (ALP) catalytic chemistry would then trigger the transition of the interparticle interplay from the CdS QDs-Au NPs to the CdS QDs-Ag NPs systems for the microRNA detection due to the dependence of the photocurrent quenching on the target concentration. This work not only provided a unique method for EPI generation among the PEC nanosystems but also offered a versatile and general protocol for future PEC bioanalysis development.

Protein Binding Bends the Gold Nanoparticle Capped DNA Sequence: Toward Novel Energy-Transfer-Based Photoelectrochemical Protein Detection.

In this work, we present a novel energy-transfer (ET)-based photoelectrochemical (PEC) probing of DNA-protein interactions, which associates intimately with many important intracellular processes in transcriptional regulatory networks. Specifically, Au nanoparticles (NPs) were confined onto the CdS quantum dots (QDs) functionalized PEC surface by the formation of duplex DNA, the subsequent binding of the TATA binding protein (TBP) and the resulting distortion of the Au NPs capped DNA sequence could adjust the interparticle distance and thereby modulate the PEC performance of CdS QDs through the ET process between the CdS QDs and Au NPs. Using the duplex DNA sequence as a rigid spacer, the relationship between the photocurrent quenching effect and the spacing distance was also studied and some experimental conditions were optimized, on the basis of which a novel ET-based PEC TBP biosensor was realized with high sensitivity and selectivity.

Simultaneous Photoelectrochemical Immunoassay of Dual Cardiac Markers Using Specific Enzyme Tags: A Proof of Principle for Multiplexed Bioanalysis.

In this Letter, on the basis of the CdS quantum dots functionalized TiO2 nanotubes electrode, we proposed a simultaneous photoelectrochemical (PEC) immunoassay of dual cardiac markers using specific enzyme tags of alkaline phosphatase (ALP) and acetylcholine esterase (AChE). ALP and AChE were integrated into the PEC system through the sandwich immunobinding and could specifically catalyze the hydrolysis of ascorbic acid 2-phosphate (AAP) or the acetylthiocholine (ATC) to in situ generate ascorbic acid (AA) or thiocholine (TC) for sacrificial electron donating. These two enzymes were thus used to differentiate the signals of two cardiac targets in connection with the sandwich immunorecognition and PEC responses to the corresponding electron donors. This strategy demonstrates a proof of principle for the successful integration of dual enzyme tags with PEC immunoassay that can potentially provide a general format for multiplexed PEC bioanalysis.

An ultrasensitive energy-transfer based photoelectrochemical protein biosensor.

Using single stranded DNA (ssDNA) as a distance controller and Au nanoparticles (NPs) functionalized with ssDNA as novel energy-transfer nanoprobes, an ultrasensitive energy-transfer based photoelectrochemical protein biosensor was realized.

A new visible-light-driven photoelectrochemical biosensor for probing DNA-protein interactions.

Based on the assay of DNA binding proteins upon visible light irradiation, a photoelectrochemical sensor was constructed for successfully probing a DNA-protein interaction for the first time.

Folding-based photoelectrochemical biosensor: binding-induced conformation change of a quantum dot-tagged DNA probe for mercury(II) detection.

Using CdS QD-tagged mercury-specific oligonucleotides, a novel folding-based photoelectrochemical sensor has been successfully fabricated for reagentless and highly sensitive Hg(2+) detection.

Bismuthoxyiodide nanoflakes/titania nanotubes arrayed p-n heterojunction and its application for photoelectrochemical bioanalysis.

We have developed sensitive detection of cancer biomarker vascular endothelial growth factor (VEGF) using the p-n heterojunction comprised of p-type BiOI nanoflakes (NFs) array and n-type TiO2 nanotubes (NTs) array. Due to the unique arrayed structure and the synergy effect of photoelectrochemistry in the formed p-n junction, the synthesized configuration has superior excitation efficiency and thus excellent photoresponsibility. Then, the fabricated p-n heterojunction was integrated with an exquisite bioassay protocol for addressing VEGF using a sandwich immunoassay with glucosedehydrogenase (GDH) as the enzyme tags. Due to the excellent performance of BiOI NFs array/TiO2 NTs array and the ingenious signaling mechanism, the proposed system could achieve the sensitive and specific VEGF detection. This work not only presents a simple BiOI NFs array/TiO2 NTs array p-n heterojunction for general applications in the broad photochemistry areas, but also opens a different horizon for current development of advanced PEC biomolecular detection.

Acetylcholine esterase antibodies on BiOI nanoflakes/TiO2 nanoparticles electrode: a case of application for general photoelectrochemical enzymatic analysis.

To date, almost all the established photoelectrochemical (PEC) enzymatic biosensors require the surface-confinement procedure to immobilize enzyme as biorecogniton element for probing various analytes of interest. This Letter develops a novel example without such necessity. Specifically, we first prepared a BiOI nanoflakes (NFs)/TiO2 nanoparticles (NPs) p-n heterojunction as the photoelectrode, on the basis of which acetylcholine esterase (AChE) antibody was introduced via the bridging of protein A. In such a system, enzyme could keep its optimal state in the solution if in the absence of inhibitor; otherwise, the degree of enzyme inhibition would correlate closely with the concentration of inhibitor. After immunoreaction between AChE and its antibody, the inhibitor concentration could then be determined by the biocatalytic reaction-controlled PEC response. Integrated with other enzyme-based biosystems, this simple configuration could serve as a general method for assaying enzyme inhibition or activities.

In situ modification of a semiconductor surface by an enzymatic process: a general strategy for photoelectrochemical bioanalysis.

Usually, the photoelectrochemical (PEC) bioanalysis necessitates ready photoactive materials as signal sources to convert the specific biological events into electrical signals. Herein, the first PEC bioanalysis without the necessity of ready visible-light-active species was demonstrated. We use an enzyme catalytic process to couple with the unique surface chemistry of semiconductive nanocrystalline, whereby its electronic properties could be modified spontaneously during the enzymatic reaction. Specifically, the enzymatic hydrolysis of ascorbic acid 2-phosphate by alkaline phosphatase is allowed to interact on the TiO2 nanoparticles (NPs) matrix. PEC tests reveal that the self-coordination of the biocatalyzed enediol-ligands onto the undercoordinated surface defect sites would in situ form a ligand-to-metal charge transfer (CT) complex, endowing the inert semiconductor with strong absorption bands in the visible region, and hence underlying a novel and general PEC bioanalysis strategy.

In situ enzymatic ascorbic acid production as electron donor for CdS quantum dots equipped TiO2 nanotubes: a general and efficient approach for new photoelectrochemical immunoassay.

In this work, a novel photoelectrochemical (PEC) immunoanalysis format was developed for sensitive and specific detection of prostate-specific antigen (PSA) based on an in situ electron donor producing approach. Thioglycolic acid-capped CdS quantum dots (QDs) equipped TiO(2) nanotubes (NTs) were fabricated via a facile electrostatic adsorption method. The coupling of CdS QDs and TiO(2) NTs results in an enhanced excitation and photo-to-electric conversion efficiency. Using alkaline phosphatase catalytic chemistry to in situ generate ascorbic acid for electron donating, an exquisite immunosandwich protocol was successfully constructed for the PSA assay due to the dependence of the photocurrent signal on the concentration of electron donor. This work opens a different perspective for transducer design in PEC detection and provides a general format for future development of PEC immunoanalysis.

Highly sensitive photoelectrochemical immunoassay with enhanced amplification using horseradish peroxidase induced biocatalytic precipitation on a CdS quantum dots multilayer electrode.

Herein we demonstrate the protocol of a biocatalytic precipitation (BCP)-based sandwich photoelectrochemical (PEC) horseradish peroxidase (HRP)-linked immunoassay on the basis of their synergy effect for the ultrasensitive detection of mouse IgG (antigen, Ag) as a model protein. The hybrid film consisting of oppositely charged polyelectrolytes and CdS quantum dots (QDs) is developed by the classic layer by layer (LbL) method and then employed as the photoactive antibody (Ab) immobilization matrix for the subsequent sandwich-type Ab-Ag affinity interactions. Improved sensitivity is achieved through using the bioconjugates of HRP-secondary antibodies (Ab(2)). In addition to the much enhanced steric hindrance compared with the original one, the presence of HRP would further stimulate the BCP onto the electrode surface for signal amplification, concomitant to a competitive nonproductive absorption that lowers the photocurrent intensity. As a result of the multisignal amplification in this HRP catalyzed BCP-based PEC immunoassay, it possesses excellent analytical performance. The antigen could be detected from 0.5 pg/mL to 5.0 ng/mL with a detection limit of 0.5 pg/mL.