Effectiveness of fecal DNA syndecan-2 methylation testing for detection of colorectal cancer in a high-risk Chinese population.

BACKGROUND: Colorectal cancer (CRC) is among the most prevalent and life-threatening malignancies worldwide. Syndecan-2 methylation (mSDC2) testing has emerged as a widely used biomarker for early detection of CRC in stool and serum samples. Cancer (CRC) is among the most prevalent and life-threatening malignancies worldwide. mSDC2 testing has emerged as a widely used biomarker for early detection of CRC in stool and serum samples. AIM: To validate the effectiveness of fecal DNA mSDC2 testing in the detection of CRC among a high-risk Chinese population to provide evidence-based data for the development of diagnostic and/or screening guidelines for CRC in China. METHODS: A high-risk Chinese cohort consisting of 1130 individuals aged 40-79 years was selected for evaluation via fecal mSDC2 testing. Sensitivity and specificity for CRC, advanced adenoma (AA) and advanced colorectal neoplasia (ACN) were determined. High-risk factors for the incidence of colorectal lesions were determined and a logistic regression model was constructed to reflect the efficacy of the test. RESULTS: A total of 1035 high-risk individuals were included in this study according to established criteria. Among them, 16 suffered from CRC (1.55%), 65 from AA (6.28%) and 189 from non-AAs (18.26%); 150 patients were diagnosed with polyps (14.49%). Diagnoses were established based upon colonoscopic and pathological examinations. Sensitivities of the mSDC2 test for CRC and AA were 87.50% and 40.00%, respectively; specificities were 95.61% for other groups. Positive predictive values of the mSDC2 test for CRC, AA and ACN were 16.09%, 29.89% and 45.98%, respectively; the negative predictive value for CRC was 99.79%. After adjusting for other high-risk covariates, mSDC2 test positivity was found to be a significant risk factor for the occurrence of ACN (P < 0.001). CONCLUSION: Our findings confirmed that offering fecal mSDC2 testing and colonoscopy in combination for CRC screening is effective for earlier detection of malignant colorectal lesions in a high-risk Chinese population.

CSANet: a lightweight channel and spatial attention neural network for grading diabetic retinopathy with optical coherence tomography angiography.

Background: Diabetic retinopathy (DR) is one of the most common eye diseases. Convolutional neural networks (CNNs) have proven to be a powerful tool for learning DR features; however, accurate DR grading remains challenging due to the small lesions in optical coherence tomography angiography (OCTA) images and the small number of samples. Methods: In this article, we developed a novel deep-learning framework to achieve the fine-grained classification of DR; that is, the lightweight channel and spatial attention network (CSANet). Our CSANet comprises two modules: the baseline model, and the hybrid attention module (HAM) based on spatial attention and channel attention. The spatial attention module is used to mine small lesions and obtain a set of spatial position weights to address the problem of small lesions being ignored during the convolution process. The channel attention module uses a set of channel weights to focus on useful features and suppress irrelevant features. Results: The extensive experimental results for the OCTA-DR and diabetic retinopathy analysis challenge (DRAC) 2022 data sets showed that the CSANet achieved state-of-the-art DR grading results, showing the effectiveness of the proposed model. The CSANet had an accuracy rate of 97.41% for the OCTA-DR data set and 85.71% for the DRAC 2022 data set. Conclusions: Extensive experiments using the OCTA-DR and DRAC 2022 data sets showed that the proposed model effectively mitigated the problems of mutual confusion between DRs of different severity and small lesions being neglected in the convolution process, and thus improved the accuracy of DR classification.

Deep-learning segmentation method for optical coherence tomography angiography in ophthalmology.

PURPOSE: The optic disc and the macular are two major anatomical structures in the human eye. Optic discs are associated with the optic nerve. Macular mainly involves degeneration and impaired function of the macular region. Reliable optic disc and macular segmentation are necessary for the automated screening of retinal diseases. METHODS: A swept-source OCTA system was designed to capture OCTA images of human eyes. To address these segmentation tasks, first, we constructed a new Optic Disc and Macula in fundus Image with optical coherence tomography angiography (OCTA) dataset (ODMI). Second, we proposed a Coarse and Fine Attention-Based Network (CFANet). RESULTS: The five metrics of our methods on ODMI are 98.91 % , 98.47 % , 89.77 % , 98.49 % , and 89.77 % , respectively. CONCLUSIONS: Experimental results show that our CFANet has achieved good performance on segmentation for the optic disc and macula in OCTA.

Septin 9 methylation analysis of lymph node micrometastases for predicting relapse of colorectal cancer.

BACKGROUND: Molecular markers for the detection of lymph node micrometastases of malignant tumors have been extensively investigated. However, epigenetic signatures have rarely been reported for identification of metastatic lymph nodes and disease relapse. Septin 9 is the most frequently reported hypermethylated gene in colorectal cancer (CRC). This study aimed to assess the clinical relevance of Septin 9 methylation in regional lymph nodes in recurrence/metastases of CRC. METHODS: We analyzed Septin 9 methylation of DNA from resected lymph nodes in 75 CRC patients with or without tumor recurrence using quantitative methylation-sensitive PCR (qMS-PCR). RESULTS: Of the 30 histologically negative lymph node CRC patients without recurrence (group 1), methylated Septin 9 was detected in 3 (10 %) cases. The positivity rate of methylated Septin 9 in group 2 containing 30 histologically node-negative CRC patients with recurrence was 30 % (9/30). For group 3, lymphatic invasion as well as tumor recurrence, 11 (73 %) out of 15 subjects had Septin 9 methylation-positive lymph nodes. Moreover, patients in group 3 had a higher level of methylated Septin 9 compared to subjects in group 1 and group 2 (p < 0.05). In addition, CRC patients with Septin 9 methylation in lymph nodes had significantly reduced survival (Log-rank P < 0.0001). CONCLUSION: Our data support the predictive role of Septin 9 methylation analysis of lymph node micrometastases for tumor relapse after surgery.

circIFITM1/miR-802/Foxp1 Axis Participates in Proliferation and Invasion of Lovo Cells.

Objective: To explore the role of circIFITM1 and its potential molecular mechanism in colon cancer. Methods: The circIFITM1 in human samples and cell lines of colon cancer was measured via RT-PCR. The cyclicity of circIFITM1 was confirmed by agarose gel electrophoresis and Sanger sequencing, and the stability of circIFITM1 was confirmed by actinomycin D assay. The proliferative and invasive ability was detected by the CCK-8 assay and Transwell assay, respectively. RNA pull-down assay confirmed a combination of circIFITM1 and miRNA. Dual-luciferase reporter gene was used to detect the direct relationship between miRNA and the target gene. Results: circIFITM1 originated from the maternal gene IFITM1and had high stability. It was resistant to processing by actinomycin D. Upregulating circIFITM1 facilitated the proliferation and invasion of Lovo cells, while interfering with circIFITM1 expression inhibited them. circIFITM1 interacted with miR-802, and miR-802 targeted the 3'UTR of FOXP1. The overexpression of circIFITM1 downregulated miR-802 and upregulated FOXP1. Conclusion: circIFITM1 facilitates the proliferative and invasive abilities via miR-802/FOXP1 in Lovo cells.

The Role of Liquid Biopsy Analytes in Diagnosis, Treatment and Prognosis of Colorectal Cancer.

Colorectal cancer (CRC) is one of the most common malignant tumors of the digestive tract worldwide and is a serious threat to human life and health. CRC occurs and develops in a multi-step, multi-stage, and multi-gene process, in which abnormal gene expression plays an important role. CRC is currently diagnosed via endoscopy combined with tissue biopsy. Compared with tissue biopsy, liquid biopsy technology has received increasingly more attention and applications in the field of molecular detection due to its non-invasive, safe, comprehensive, and real-time dynamic nature. This review article discusses the application and limitations of current liquid biopsy analytes in the diagnosis, treatment, and prognosis of CRC, as well as directions for their future development.

Circular RNAs and Their Role in Exosomes.

As a novel class of endogenous non-coding RNAs discovered in recent years, circular RNAs (circRNAs) are highly conserved and stable covalently closed ring structures with no 5'-end cap or 3'-end poly(A) tail. CircRNAs are formed by reverse splicing, mainly by means of a noose structure or intron complementary pairing. Exosomes are tiny discoid vesicles with a diameter of 40-100 nm that are secreted by cells under physiological and pathological conditions. Exosomes play an important role in cell-cell communication by carrying DNA, microRNAs, mRNAs, proteins and circRNAs. In this review, we summarize the biological functions of circRNAs and exosomes, and further reveal the potential roles of exosomal circRNAs in different diseases, providing a scientific basis for the diagnosis, treatment, and prognosis of a wide variety of diseases.

The PRIDE database resources in 2022: a hub for mass spectrometry-based proteomics evidences.

The PRoteomics IDEntifications (PRIDE) database (https://www.ebi.ac.uk/pride/) is the world's largest data repository of mass spectrometry-based proteomics data. PRIDE is one of the founding members of the global ProteomeXchange (PX) consortium and an ELIXIR core data resource. In this manuscript, we summarize the developments in PRIDE resources and related tools since the previous update manuscript was published in Nucleic Acids Research in 2019. The number of submitted datasets to PRIDE Archive (the archival component of PRIDE) has reached on average around 500 datasets per month during 2021. In addition to continuous improvements in PRIDE Archive data pipelines and infrastructure, the PRIDE Spectra Archive has been developed to provide direct access to the submitted mass spectra using Universal Spectrum Identifiers. As a key point, the file format MAGE-TAB for proteomics has been developed to enable the improvement of sample metadata annotation. Additionally, the resource PRIDE Peptidome provides access to aggregated peptide/protein evidences across PRIDE Archive. Furthermore, we will describe how PRIDE has increased its efforts to reuse and disseminate high-quality proteomics data into other added-value resources such as UniProt, Ensembl and Expression Atlas.

Sodium houttuyfonate attenuates neurological defects after traumatic brain injury in mice via inhibiting NLRP3 inflammasomes.

Sodium houttuyfonate (SH) is a chemical compound synthesized by houttuynin and sodium bisulfite. As it has antinflammatory effects, SH has been widely used to treat autoimmune diseases, including post events following traumatic brain injury (TBI). Meanwhile, NOD-like receptor with pyrin domain containing-3 (NLRP3) inflammasomes in microglia may play a central role in TBI. But to date, the intracellular mechanisms involved in the anti-inflammatory effects of SH in TBI remain unknown, especially whether regulating NLRP3. To gain an insight into this possibility, we conducted cell culture and biochemical studies on the effect of SH on NLRP3 inflammasome in microglia. The results showed that SH inhibited TLR4 and NLRP3 inflammasome activation in the microglia cell. In parallel, phosphorylation of ERK and NF-κB p65, which play a key role in NLRP3 inflammasome formation, was decreased. Intraperitoneal injection of SH into TBI mice significantly reduced the modified neurological severity score (mNSS), as well as the degree of microglia apoptosis post-controlled cortical impact (CCI). Immunohistochemistry, Western blot analysis, and reverse-transcription polymerase chain reaction (RT-PCR) revealed that SH markedly reduced NLRP3 inflammasome activation, TLR4 activity, phosphorylation of ERK and NF-κB. Moreover, SH significantly inhibited microglia activation post-CCI, but effectively promoted the astrocyte activation and angiopoiesis. Taken together, our research provides evidence that SH attenuated neurological deficits post TBI through inhibiting NLRP3 inflammasome activation, via influencing the TLR4/NF-κB signaling pathway. These findings explain the intracellular mechanism of the anti-inflammatory activity caused by SH treatment following TBI.

Lamella-nanostructured eutectic zinc-aluminum alloys as reversible and dendrite-free anodes for aqueous rechargeable batteries.

Metallic zinc is an attractive anode material for aqueous rechargeable batteries because of its high theoretical capacity and low cost. However, state-of-the-art zinc anodes suffer from low coulombic efficiency and severe dendrite growth during stripping/plating processes, hampering their practical applications. Here we show that eutectic-composition alloying of zinc and aluminum as an effective strategy substantially tackles these irreversibility issues by making use of their lamellar structure, composed of alternating zinc and aluminum nanolamellas. The lamellar nanostructure not only promotes zinc stripping from precursor eutectic Zn88Al12 (at%) alloys, but produces core/shell aluminum/aluminum sesquioxide interlamellar nanopatterns in situ to in turn guide subsequent growth of zinc, enabling dendrite-free zinc stripping/plating for more than 2000 h in oxygen-absent aqueous electrolyte. These outstanding electrochemical properties enlist zinc-ion batteries constructed with Zn88Al12 alloy anode and KxMnO2 cathode to deliver high-density energy at high levels of electrical power and retain 100% capacity after 200 hours.

Lipid-Wrapped Upconversion Nanoconstruct/Photosensitizer Complex for Near-Infrared Light-Mediated Photodynamic Therapy.

Photodynamic therapy (PDT) is a noninvasive medical technology that has been applied in cancer treatment where it is accessible by direct or endoscope-assisted light irradiation. To lower phototoxicity and increase tissue penetration depth of light, great effort has been focused on developing new sensitizers that can utilize red or near-infrared (NIR) light for the past decades. Lanthanide-doped upconversion nanoparticles (UCNPs) have a unique property to transduce NIR excitation light to UV-vis emission efficiently. This property allows some low-cost, low-toxicity, commercially available visible light sensitizers, which originally are not suitable for deep tissue PDT, to be activated by NIR light and have been reported extensively in the past few years. However, some issues still remain in the UCNP-assisted PDT platform such as colloidal stability, photosensitizer loading efficiency, and accessibility for targeting ligand installation, despite some advances in this direction. In this study, we designed a facile phospholipid-coated UCNP method to generate a highly colloidally stable nanoplatform that can effectively load a series of visible light sensitizers in the lipid layers. The loading stability and singlet oxygen generation efficiency of this sensitizer-loaded lipid-coated UCNP platform were investigated. We also have demonstrated the enhanced cellular uptake efficiency and tumor cell selectivity of this lipid-coated UCNP platform by changing the lipid dopant. On the basis of the evidence of our results, the lipid-complexed UCNP nanoparticles could serve as an effective photosensitizer carrier for NIR light-mediated PDT.

Quantitative Analysis of Carbon Steel with Multi-Line Internal Standard Calibration Method Using Laser-Induced Breakdown Spectroscopy.

A multi-line internal standard calibration method is proposed for the quantitative analysis of carbon steel using laser-induced breakdown spectroscopy (LIBS). A procedure based on the method was adopted to select the best calibration curves and the corresponding emission lines pairs automatically. Laser-induced breakdown spectroscopy experiments with carbon steel samples were performed, and C, Cr, and Mn were analyzed via the proposed method. Calibration curves of these elements were constructed via a traditional single line internal standard calibration method and a multi-line internal standard calibration method. The calibration curves obtained were evaluated with the determination coefficient, the root mean square error of cross-validation, and the average relative error of cross-validation. All of the parameters were improved significantly with the proposed method. The results show that accurate and stable calibration curves can be obtained efficiently via the multi-line internal standard calibration method.

[Multi-Element Detection in Molten Steel with Laser-Induced Breakdown Spectroscopy].

On-line element content detection in iron and steel industry is one of the key techniques to ensure the quality in iron and steel metallurgy. Laser Induced Breakdown Spectroscopy (LIBS) has been applied to on-line components detection in molten steel. We have built LIBS system for components detection of molten steel in laboratory. The system consists of a Q-switched Nd∶YAG laser (repetition rate 10 Hz, wavelength 1 064 nm, pulse length 10 ns, pulse energy about 120 mJ), high frequency induction furnace (temperature 1 600 ℃), spectrometer (wavelength range 186～310 nm, spectral resolution 0.1 nm), laser focusing and spectral signal collecting system. Multi-elements were detected in molten steel with the application of deep-UV detector coating and solarization resistant fibers. According to the calibration curves of C, S, Mn and Cr, the limit of detections are 169, 15, 58.9 and 210 µg·g-1 respectively. The R-squares of calibration curves of C, S, Mn, and Cr are better than 0.96 by using appropriate analytical lines and reference lines. At the same time, through the comparison of different elements, we find the best calibration curve of different element need different delay conditions.