Period 2 Suppresses the Malignant Cellular Behaviors of Colorectal Cancer Through the Epithelial-Mesenchymal Transformation Process.

INTRODUCTION: The PER2 (Period circadian regulator 2) gene is related to the circadian clock, and it has been deemed as a suppressor gene in osteosarcoma and lung carcinoma. However, the part of PER2 in CRC (colorectal cancer) needs to be further determined. METHODS: First, we collected clinical samples to detect PER2 expression in CRC. Then, we used cell transfection to knock down PER2 expression in CRC cell lines and performed a series of functional experiments to elucidate the effects of PER2 on CRC cells. We next verified whether PER2 affects the epithelial-mesenchymal transformation (EMT) process in CRC by conducting quantitative real-time PCR and western blotting. RESULTS: In the research, we revealed that the expression of PER2 decreased in CRC clinical samples. In addition, knocking down PER2 expression caused CRC cells to acquire malignant biological features. Finally, we found that PER2 knockdown may activate the Snail/Slug axis through inhibiting p53, therefore promote the activation of the EMT pathway. CONCLUSION: In conclusion, low PER2 expression reinforces migration and activates EMT in CRC, suggesting that PER2 is closely related to CRC development and could be used as a potential treatment site in the clinic.

Identification of crucial genes of pyrimidine metabolism as biomarkers for gastric cancer prognosis.

BACKGROUND: Metabolic reprogramming has been reported in various kinds of cancers and is related to clinical prognosis, but the prognostic role of pyrimidine metabolism in gastric cancer (GC) remains unclear. METHODS: Here, we employed DEG analysis to detect the differentially expressed genes (DEGs) in pyrimidine metabolic signaling pathway and used univariate Cox analysis, Lasso-penalizes Cox regression analysis, Kaplan-Meier survival analysis, univariate and multivariate Cox regression analysis to explore their prognostic roles in GC. The DEGs were experimentally validated in GC cells and clinical samples by quantitative real-time PCR. RESULTS: Through DEG analysis, we found NT5E, DPYS and UPP1 these three genes are highly expressed in GC. This conclusion has also been verified in GC cells and clinical samples. A prognostic risk model was established according to these three DEGs by Univariate Cox analysis and Lasso-penalizes Cox regression analysis. Kaplan-Meier survival analysis suggested that patient cohorts with high risk score undertook a lower overall survival rate than those with low risk score. Stratified survival analysis, Univariate and multivariate Cox regression analysis of this model confirmed that it is a reliable and independent clinical factor. Therefore, we made nomograms to visually depict the survival rate of GC patients according to some important clinical factors including our risk model. CONCLUSION: In a word, our research found that pyrimidine metabolism is dysregulated in GC and established a prognostic model of GC based on genes differentially expressed in pyrimidine metabolism.

Metallic Inverse Opals: An Electrochemiluminescence enhanced Substrate for Sensitive Bioanalysis.

Here, we proposed a novel local surface plasmon resonance (LSPR) enhanced ECL strategy based on the metallic inverse opals and Ru(bpy)32+-doped silica nanoparticles (RuSi NPs). Gold inverse opals (GIOs), as a plasmonic array, could interact with the ECL of RuSi NPs and excite the electromagnetic (EM) field at the gold surface. The triggered EM field could enhance the ECL emission of RuSi NPs. We compared the electrochemical and ECL performances of RuSi NPs modified on the gold electrodes with different surface morphologies and found that the ECL emission of RuSi NPs patterned at the inner surface of GIOs exhibited the highest intensity. The finite-difference time-domain (FDTD) simulations indicated that the EM field was related to the surface morphology of the metallic nanostructure, and the highest EM field was observed at the inner surface of the GIOs. Because of the superior ECL performances, the inner surfaces of GIOs were developed for nucleic acid detection with a detection limit of 3.3 fM (S/N = 3), which shows great promise for bioanalysis.

Electrochemiluminescence Energy Resonance Transfer System between RuSi Nanoparticles and Hollow Au Nanocages for Nucleic Acid Detection.

This paper describes an electrochemiluminescence resonance energy transfer (ECL-RET) system using Ru(bpy)32+-doped silica nanoparticles (RuSi NPs) as the ECL donor and hollow Au nanocages as the ECL acceptor. Tetrahedron DNA (TD) was used to construct the biosensing interface and control the distance (4.8 nm) between the ECL donor-acceptor pairs. The surface plasmon resonance (SPR) nanostructures, Au nanocages were assembled via the hairpin based sandwich assay. Due to the well overlap between the plasmon absorption spectrum of Au nanocages (628 nm) and the ECL emission spectrum of RuSi NPs (620 nm), high efficient energy transfer could occur. Subsequent cyclic DNA amplification further increased the binding amount of Au nanocages. Since the ECL inhibition is closely related with the binding amount of Au nanocages, a general "signal-off" ECL bioassay could thus be tailored with high sensitivity. At the optimized conditions, this ECL-RET system performed well with great stability and repeatability for nucleic acid detection in the range from 1.0 fM to 10 pM. This work manifested the great promise of hollow Au nanocages for an ECL-RET biosensor that to the best of our knowledge has not been reported. We believe that it could inspire more interest in the design and development of numerous other SPR nanostructures for advanced ECL-RET biosensors.

Ultrasmall Nanopipette: Toward Continuous Monitoring of Redox Metabolism at Subcellular Level.

Ionic current rectification (ICR) based nanopipettes allow accurate monitoring of cellular behavior in single living cells. Herein, we proposed a 30 nm nanopipette functionalized with G-quadruplex DNAzyme as an efficient biomimetic recognizer for ROS generation at subcellular level via the changes of current-voltage relationship. Taking advantages of the ultra-small tip, the nanopipette could penetrate into a single living cell repeatedly or keep measuring for a long time without compromising the cellular functions. Coupled with precision nanopositioning system, generation of ROS in mitochondria in response to cell inflammation was determined with high spatial resolution. Meanwhile, the changes of aerobic metabolism in different cell lines under drug-induced oxidative stress were monitored continuously. We believe that the ICR-nanopipette could be developed as a powerful approach for the study of cellular activities via electrochemical imaging in living cells.

Synergetic surface enhancement of quantum dots-based electrochemiluminescence with photonic crystal light scattering and metal surface plasmon resonance for sensitive bioanalysis.

Noble metal nanostructures and photonic crystals (PhCs) have been widely investigated as substrates for constructing surface enhanced electrochemiluminescence (SE-ECL) biosensors. However, their applications are hindered by the limited enhancement intensity of surface plasmon resonance (SPR) and an incomplete mechanism for the photonic enhancement effect. Hence, developing a novel SE-ECL strategy with better signal enhanced capability and enriching our understanding of the intrinsic mechanisms for efficient bioanalysis is extremely urgent. Here, a synergistic SE-ECL strategy was developed for the sensitive determination of prostate specific antigen (PSA) protein. The randomly arranged polystyrene (r-PS) spheres and PS PhC arrays were applied to enhance the ECL emission of cadmium sulfide quantum dots (CdS QDs) and the results suggested that the PhC arrays displayed superior intensity (0.22) than the r-PS interface (0.10). Au nanoparticles (NPs) were introduced onto the two kinds of surfaces and further boosted the ECL intensity. According to the ECL measurements, Au NPs modified at the r-PS surface exhibited only a slight increase (0.13), while the PhC arrays showed approximately 5-fold enhancement (0.92), benefiting from the synergistic enhancement. The finite-difference time-domain (FDTD) simulation indicated that the ECL enhancement was ascribed to the coupled electromagnetic (EM) field at the surfaces of PS PhCs and Au NPs. The SE-ECL could achieve a detection range from 1 pg/mL to 1 µg/mL with a detection limit of 0.41 pg/mL (S/N = 3). This study provides the first combination of PhC arrays and metal surface plasmon nanostructure for the synergetic enhancement of SE-ECL systems. It opens a new avenue for the rational design of advanced ECL biosensors and shows great perspective for clinical diagnosis.

AIE fluorogen-based oxidase-like fluorescence nanozyme-integrated smartphone for monitoring the freshness authenticity of soy products.

Food safety concerns about the authenticity of soy product freshness have increased due to high demand from public. Developing an accurate and convenient monitoring method for freshness authenticity is crucial for safeguarding food safety. From this motive, this study employed PtPd NPs to encapsulate tetraphenylethylene (TPE) for engineering an AIE-based fluorescent nanozyme (PtPd NPs@TPE) with oxidase-like activity, achieving the ratiometric fluorescence monitoring of putrescine (PUT) to judge the freshness authenticity of soy products. In this design, PUT acted as an antioxidant and inhibited the oxidation process of PtPd NPs@TPE to o-phenylenediamine (OPD), leading to the reduction of oxidative product 2,3-diaminophenothiazine (DAP) alone with the weaken of yellow fluorescence from DAP at 552 nm and bright of bule fluorescence from PtPd NPs@TPE at 442 nm. On this basis, a ratiometric fluorescence strategy integrated with smartphone-based sensor was developed for PUT with acceptable results to combat food freshness fraud of soy products.

Colorimetric and ECL dual-mode aptasensor for smartphone-based onsite sensitive detection of aflatoxin B1 in combination with ZnO@MWCNTs/g-C3N4 nanosheets and CuO@CuPt nanocomposites.

The development of dual-mode strategies with superior sensitivity and accuracy have garnered increasing attention for researchers in Aflatoxin B1 (AFB1) analysis. Herein, a colorimetric-electrochemiluminescence (ECL) dual-mode biosensor was constructed for onsite and ultrasensitive determination of AFB1. The multi-wall carbon nanotubes (MWCNTs) were integrated with the ZnO metal organic frameworks (MOFs) to accelerate the electron transfer and boost the ECL intensity of g-C3N4 nanoemitters. Through the aptamer-based DNA sandwich assay, the CuO@CuPt nanocomposites were introduced onto the electrode and acted as the dual functional signal nanoprobes. Due to the good spectrum overlap between the CuO@CuPt nanoprobes and g-C3N4 nanosheets, ECL signal could be efficiently quenched. Additionally, the CuO@CuPt nanoprobes show superior catalytic properties towards the TMB and H2O2 colorimetric reactions, and an obvious color alteration from colorless to blue can be observed using the smartphone. Under optimized conditions, a sensitive and accurate dual-mode analysis of the AFB1 was accomplished with the colorimetric detection limit of 3.26 fg/mL and ECL detection limit of 0.971 fg/mL (S/N = 3). This study combines innovative nanomaterial properties of ZnO@MWCNTs, g-C3N4 and CuO@CuPt for ultrasensitive dual-mode detection, which offers new opportunities for the innovative engineering of the dual-mode sensors and demonstrates significant potential in food safety analysis.

External Beam Radiation therapy After Transarterial Chemoembolization Versus Transarterial Chemoembolization Alone for Treatment of Inoperable Hepatocellular Carcinoma: A Randomized Phase 3 Trial.

PURPOSE: To compare the outcomes of transarterial chemoembolization (TACE) alone with those of TACE combined with external beam radiation therapy (EBRT) in patients with hepatocellular carcinoma (HCC) in a multicenter randomized study. METHODS AND MATERIALS: From 2017 to 2022, 74 HCC patients with tumors confined to the liver without vascular invasion were treated with either TACE only (TACE group, 39 patients) or TACE combined with EBRT (TACE + EBRT group, 35 patients). The primary outcome measured was overall survival (OS). Secondary outcomes included progression-free survival (PFS), local tumor control, and the assessment of treatment-related toxicity. RESULTS: Due to slow accrual, the trial was closed prematurely after enrolling 74 patients. All patients received 2 cycles of TACE before randomization. The TACE and TACE + EBRT groups showed comparable patient and tumor characteristics. The TACE group underwent a median of 3 TACE cycles, and the TACE + EBRT group received 2 cycles of TACE, and a median of 5500 cGy in 15 fractions. For the TACE group, the median local control (LC) duration was 13.1 months, whereas for the TACE + EBRT group, the median LC was not achieved (P < .001). The PFS was recorded at 11.6 months in the TACE group compared with 15.4 months in the TACE + EBRT group (P = .072). The median OS reached 36.8 months for the TACE group and extended to 47.1 months for the TACE + EBRT group (P = .654). The incidence of toxicity was comparable between both groups. CONCLUSIONS: Although the number of patients enrolled in this clinical trial did not meet expectations. TACE combined with EBRT was shown to be more effective than TACE alone in improving LC without increasing toxicity, whereas PFS and OS were slightly improved. TACE + EBRT can be used as a standard treatment option for patients with inoperable but confined intrahepatic HCC.

Altered Patterns of Functional Connectivity and Causal Connectivity in Salience Subnetwork of Subjective Cognitive Decline and Amnestic Mild Cognitive Impairment.

The subjective cognitive decline (SCD) may last for decades prior to the onset of dementia and has been proposed as a risk population for development to amnestic mild cognitive impairment (aMCI) and Alzheimer disease (AD). Disruptions of functional connectivity and causal connectivity (CC) in the salience network (SN) are generally perceived as prominent hallmarks of the preclinical AD. Nevertheless, the alterations in anterior SN (aSN), and posterior SN (pSN) remain unclear. Here, we hypothesized that both the functional connectivity (FC) and CC of the SN subnetworks, comprising aSN and pSN, were distinct disruptive in the SCD and aMCI. We utilized resting-state functional magnetic resonance imaging to investigate the altered FC and CC of the SN subnetworks in 28 healthy controls, 23 SCD subjects, and 29 aMCI subjects. In terms of altered patterns of FC in SN subnetworks, aSN connected to the whole brain was significantly increased in the left orbital superior frontal gyrus, left insula lobule, right caudate lobule, and left rolandic operculum gyrus (ROG), whereas decreased FC was found in the left cerebellum superior lobule and left middle temporal gyrus when compared with the HC group. Notably, no prominent statistical differences were obtained in pSN. For altered patterns of CC in SN subnetworks, compared to the HC group, the aberrant connections in aMCI group were separately involved in the right cerebellum inferior lobule (CIL), right supplementary motor area (SMA), and left ROG, whereas the SCD group exhibited more regions of aberrant connection, comprising the right superior parietal lobule, right CIL, left inferior parietal lobule, left post-central gyrus (PG), and right angular gyrus. Especially, SCD group showed increased CC in the right CIL and left PG, whereas the aMCI group showed decreased CC in the left pre-cuneus, corpus callosum, and right SMA when compared to the SCD group. Collectively, our results suggest that analyzing the altered FC and CC observed in SN subnetworks, served as impressible neuroimaging biomarkers, may supply novel insights for designing preclinical interventions in the preclinical stages of AD.