Advances in Microfluidic Paper-Based Analytical Devices (µPADs): Design, Fabrication, and Applications.

Microfluidic Paper-based Analytical Devices (µPADs) have emerged as a new class of microfluidic systems, offering numerous advantages over traditional microfluidic chips. These advantages include simplicity, cost-effectiveness, stability, storability, disposability, and portability. As a result, various designs for different types of assays are developed and investigated. In recent years, µPADs are combined with conventional detection methods to enable rapid on-site detection, providing results comparable to expensive and sophisticated large-scale testing methods that require more time and skilled personnel. The application of µPAD techniques is extensive in environmental quality control/analysis, clinical diagnosis, and food safety testing, paving the way for on-site real-time diagnosis as a promising future development. This review focuses on the recent research advancements in the design, fabrication, material selection, and detection methods of µPADs. It provides a comprehensive understanding of their principles of operation, applications, and future development prospects.

[Health Risk Assessment of Heavy Metals in Soils of a City in Guangdong Province Based on Source Oriented and Monte Carlo Models].

Taking a city in Guangdong Province as the research area, the concentration and spatial distribution characteristics of heavy metals in the surface soil were studied to clarify the situation of soil heavy metal pollution and priority control factors, providing basic data for the prevention and control of soil heavy metal pollution in the city. The content characteristics of heavy metals in 221 soil samples in the city were analyzed, and the potential health risk assessment and source analysis were carried out through the Monte Carlo model, the potential health risk assessment (HRA) model, and the PMF receptor model. It was found that heavy metals ω(As), ω(Hg), ω(Cd), ω(Pb), ω(Cr), ω(Cu), ω(Ni), and ω(Zn) in the soil of the city were 18.16, 0.43, 1.46, 68.57, 98.34, 64.19, 26.53, and 257.32 mg·kg-1, respectively, with a moderate to high degree of variation. Except for Ni concentration, the soil concentrations of other heavy metal elements exceeded the background values of soil in Guangdong Province to a certain extent, and the concentrations of Cd and Zn exceeded the national secondary standards, resulting in severe heavy metal pollution; the main sources of heavy metals were industrial sources, and natural parent materials, lead battery manufacturing, transportation, artificial cultivation, and pesticide and fertilizer inputs also had an undeniable impact on the accumulation of heavy metals in the soil. Heavy metals in the soil had a certain degree of tolerable carcinogenic health risk for both children and adults, whereas non-carcinogenic risks could be ignored. The potential health risk of children was greater than that of adults, and the main exposure route was through oral intake. The input sources of pesticides and fertilizers and As should be the main controlling factors for the health risks of heavy metals in the city's soil, followed by mixed sources and Cr. There were differences in the spatial distribution characteristics and relative pollution levels of heavy metals, and it is necessary to deepen zoning monitoring and control, strengthen soil pollution prevention and control, and reduce human input of heavy metals in soil.

Tea polyphenol-derived nanomedicine for targeted photothermal thrombolysis and inflammation suppression.

Thrombotic diseases impose a significant global health burden, and conventional drug-based thrombolytic therapies are encumbered by the risk of bleeding complications. In this study, we introduce a novel drug-free nanomedicine founded on tea polyphenols nanoparticles (TPNs), which exhibits multifaceted capabilities for localized photothermal thrombolysis. TPNs were synthesized through a one-pot process under mild conditions, deriving from the monomeric epigallocatechin-3-gallate (EGCG). Within this process, indocyanine green (ICG) was effectively encapsulated, exploiting multiple intermolecular interactions between EGCG and ICG. While both TPNs and ICG inherently possessed photothermal potential, their synergy significantly enhanced photothermal conversion and stability. Furthermore, the nanomedicine was functionalized with cRGD for targeted delivery to activated platelets within thrombus sites, eliciting robust thrombolysis upon laser irradiation across diverse thrombus types. Importantly, the nanomedicine's potent free radical scavenging abilities concurrently mitigated vascular inflammation, thus diminishing the risk of disease recurrence. In summary, this highly biocompatible multifunctional nanomaterial holds promise as a comprehensive approach that combines thrombolysis with anti-inflammatory actions, offering precision in thrombosis treatment.

Exploration of carbonyl compounds in red-fleshed kiwifruit wine and perceptual interactions among non-volatile organic acids.

Carbonyl compounds are vital constituents that contribute to the flavor profile of alcoholic beverages. We examined 3-nitrophenylhydrazine as a derivatizing reagent for the measurement of 34 carbonyl compounds using UPLC-MS/MS. Adding formic acid and sodium acetate to the mobile phase significantly enhanced the detection limit of carbonyl compounds. The technique exhibited a notable extraction efficiency, yielding recovery percentages ranging from 83.6% to 117.1%, coupled with exceptional sensitivity, as evidenced by detection limits spanning from 0.07 µg/L to 4.80 µg/L. The relative standard deviation was <6.9%, indicating the precision and reliability of the analytical methodology. The method was verified by analyzing carbonyl compounds from red-fleshed kiwifruit wine. Furthermore, sensory assessment revealed that the amalgamation of tartaric acid, malic acid, and citric acid contributes to sour taste perception at sub-threshold concentrations through an additive interaction with supra-threshold non-volatile organic acids such as lactic acid and acetic acid.

[Pollution Characteristics and Risk Assessment of Polycyclic Aromatic Hydrocarbons in Soils of Guangzhou].

In order to comprehensively study the pollution characteristics of polycyclic aromatic hydrocarbons （PAHs） in soils of Guangzhou， 222 topsoil samples were collected and analyzed. The ecological risk of soil PAHs pollution was evaluated using the effect interval low/median method （ERL/ERM） and the （BaP） toxicity equivalent method， and the health risk of soil PAHs pollution was evaluated using the lifelong cancer risk increment model. The source of PAHs was analyzed using the characteristic compound ratio method and PMF model. The results indicated that： the content of surface soil （∑16PAHs） in Guangzhou was 38-11 115 µg·kg-1， with an average of 526 µg·kg-1， and 16 types of polycyclic aromatic hydrocarbon monomers showed strong variation. There was a certain degree of ecological risk of PAHs in Guangzhou， and there was already a significant ecological risk of PAHs pollution in individual sampling points， which were generally in a state of mild pollution. Based on the results of the health risk assessment， the contribution rates of total cancer risk in both adults and children were presented as follows： skin contact > ingestion of soil > respiratory intake. The health risk of children was greater than that of adults， and the overall health risk was within an acceptable range. Source analysis showed that the main sources of soil PAHs in Guangzhou were coal （37.1%）； diesel （32%）； coking （17.3%）； and mixed sources of traffic emissions， biomass combustion， and petrochemical product volatilization （13.6%）. The overall source of soil PAHs belonged to mixed sources. The research results have enriched our understanding of the pollution status of PAHs in the surface soil of Guangzhou and are helpful in promoting soil pollution prevention and control actions.

ZIF-67 based CoS2 self-assembled on graphitic carbon nitride microtubular for sensitive electrochemical detection of paraquat in fruits.

Paraquat (PQ) is a widely used and harmful herbicide that must be detected in the environment. This study reports a novel composite (CoS2-GCN) prepared by assembling cobalt disulfide (CoS2) derived from metal-organic frameworks (MOFs) on graphitic carbon nitride (GCN). An electrochemical sensor (CoS2-GCN/ glassy carbon electrode (GCE)) was successfully prepared by modifying CoS2-GCN onto a GCE to sensitively detect PQ. Different concentrations of PQ were detected using square-wave voltammetry, and the CoS2-GCN/GCE electrochemical sensor showed remarkable response signals for PQ in the range of 20 - 1000 nM and 1 - 13 µM, with a detection limit of 4.13 nM (S/N = 3). The CoS2-GCN/GCE electrochemical sensor exhibited high stability, reproducibility, and immunity to interference, which were attributed to the synergistic effects of CoS2 and GCN. In addition, the CoS2-GCN/GCE electrochemical sensor showed high applicability for the analysis of fruit samples. Therefore, the proposed sensor has potential applications in PQ detection.

Risk Factors for Distant Metastasis in T3 T4 Rectal Cancer.

Background: Distant metastasis is the leading cause of death in patients with rectal cancer. This study aims to comprehensively analyze the risk factors of distant metastasis in T3 T4 rectal cancer using magnetic resonance imaging (MRI), pathological features, and serum indicators. Methods: The clinicopathological data of 146 cases of T3 T4 rectal cancer after radical resection from January 2015 to March 2023 were retrospectively analyzed. Pre- and postoperative follow-up data of all cases were collected to screen for distant metastatic lesions. Univariate and multivariate Logistic regression methods were used to analyze the relationship between MRI features, pathological results, serum test indexes, and distant metastasis. Results: Of the 146 included patients, synchronous or metachronous distance metastasis was confirmed in 43 (29.4%) cases. The patients' baseline data and univariate analysis showed that mrEMVI, maximum tumor diameter, mr T Stage, pathological N stage, number of lymph node metastasis, cancer nodules, preoperative serum CEA, (Carcinoembryonic antigen) and CA199 were associated with distant metastasis. In the multiple logistic regression model, mrEMVI, pathological N stage, number of lymph node metastasis, maximum tumor diameter, and preoperative serum CEA were identified as independent risk factors for distant metastasis: mrEMVI [odds ratio (OR) = 3.06], pathological N stage (OR = 6.52 for N1 vs N0; OR = 63.47 for N2 vs N0), preoperative serum CEA (OR = 0.27), tumor maximum diameter (OR = 1.03), number of lymph nodes metastasis (OR = 0.62). And, the receiver operating characteristic (ROC) curve was plotted and the area under the curve was calculated (area under the curve [AUC) = 0.817, 95% CI = 0.744-0.890, P < .001]. Conclusions: mrEMVI, pathological N stage, number of lymph node metastasis, maximum tumor diameter and preoperative serum CEA are the independent risk factors for distant metastasis in T3 T4 rectal cancer. A comprehensive analysis of the risk factors for distant metastasis in rectal cancer can provide a reliable basis for formulating individualized treatment strategies, follow-up plans, and evaluating prognosis.

Leukotriene B4 receptor knockdown affects PI3K/AKT/mTOR signaling and apoptotic responses in colorectal cancer.

Colorectal cancer (CRC) presents a landscape of intricate molecular dynamics. In this study, we focused on the role of the leukotriene B4 receptor (LTB4R) in CRC, exploring its significance in the disease's progression and potential therapeutic approaches. Using bioinformatics analysis of the GSE164191 and the Cancer Genome Atlas-colorectal adenocarcinoma (TCGA-COAD) datasets, we identified LTB4R as a hub gene influencing CRC prognosis. Subsequently, we examined the relationship between LTB4R expression, apoptosis, and the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway through cellular and mice experiments. Our findings revealed that LTB4R is highly expressed in CRC samples and is pivotal for determining prognosis. In vitro experiments demonstrated that silencing LTB4R significantly impeded CRC cell viability, migration, invasion, and colony formation. Correspondingly, in vivo tests indicated that LTB4R knockdown led to markedly slower tumor growth in mice models. Further in-depth investigation revealed that LTB4R knockdown significantly amplified the apoptosis in CRC cells and upregulated the expression of apoptosis-related proteins, such as caspase-3 and caspase-9, while diminishing p53 expression. Interestingly, silencing LTB4R also resulted in a significant downregulation of the PI3K/AKT/mTOR signaling pathway. Moreover, pretreatment with the PI3K activator 740Y-P only partially attenuated the effects of LTB4R knockdown on CRC cell behavior, emphasizing LTB4R's dominant influence in CRC cell dynamics and signaling pathways. LTB4R stands out as a critical factor in CRC progression, profoundly affecting cellular behavior, apoptotic responses, and the PI3K/AKT/mTOR signaling pathway. These findings not only shed light on LTB4R's role in CRC but also establish it as a potential diagnostic biomarker and a promising target for therapeutic intervention.

Carcinosarcoma of the ovary: a case report and literature review.

Objective: Carcinosarcoma of the ovary is a rare pathological type of ovarian cancer that is highly aggressive and occurs most frequently in the female reproductive tract at the site of the uterus. Herein, we explore the clinicopathological features, diagnosis, differential diagnosis, and treatment options for carcinosarcoma of the ovary. Methods: We analyzed the clinical data of a case of carcinosarcoma, observed its histological morphology and immunohistochemical characteristics, detected the homologous recombination repair deficiency gene mutation, and reviewed the relevant literature. Results: A 76-year-old menopausal woman visited our hospital because of abdominal distension, difficulty in urination, and constipation. Ultrasonography demonstrated abnormalities in the uterus and pelvic cavity, suggesting that the patient should undergo surgery. Immunohistochemical findings of carcinosarcoma of the right ovary were as follows: CK fraction (+), vimentin fraction (+), CK5/6 foci (+), p16 (+), p53 in approximately 70% (+), WT-1 foci (+), ER foci (+), PR part (+), Her-2 (1+), CK7 fraction (+), CK20 foci (+), CD99 fraction (+), CD10 fraction (+), CD56 foci (+), c-kit foci (+), SMA part (+), desmin foci (+), PD-L1 (-), SALL4 (-), OCT3/4 (-), p63 (-), p40 (-), D2-40 (-), inhibin (-), PLAP (-), CD30 (-), and Ki67 hotspot in approximately 80% (+). The patient underwent tumor cytoreduction and adjuvant chemotherapy. Currently, she is being followed up for 16 months and has a good general condition. Conclusion: The diagnosis of carcinosarcoma relies on histopathological examination and differentiation of carcinosarcoma from immature teratoma. The current therapeutic regimen for carcinosarcoma is still based on tumor cytoreduction and platinum-containing chemotherapy; research on targeted therapy is still in progress.

CpG-Conjugated Silver Nanoparticles as a Multifunctional Nanomedicine to Promote Macrophage Efferocytosis and Repolarization for Atherosclerosis Therapy.

Atherosclerosis (AS) is a major contributor to cardiovascular diseases, necessitating the development of novel therapeutic strategies to alleviate plaque burden. Macrophage efferocytosis, the process by which macrophages clear apoptotic and foam cells, plays a crucial role in plaque regression. However, this process is impaired in AS lesions due to the overexpression of CD47, which produces a "do not eat me" signal. In this study, we investigated the potential of CpG, a toll-like receptor 9 agonist, to enhance macrophage efferocytosis for AS therapy. We demonstrated that CpG treatment promoted the engulfment of CD47-positive apoptotic cells and foam cells by macrophages. Mechanistically, CpG induced a metabolic shift in macrophages characterized by enhanced fatty acid oxidation and de novo lipid biosynthesis, contributing to its pro-efferocytic effect. To enable in vivo application, we conjugated CpG on silver nanoparticles (AgNPs) to form CpG-AgNPs, which could protect CpG from biological degradation, promote its cellular uptake, and release CpG in response to intracellular glutathione. Combining the intrinsic antioxidative and anti-inflammatory abilities of AgNPs, such nanomedicine displayed multifunctionalities to simultaneously promote macrophage efferocytosis and repolarization. In an ApoE-/- mouse model, intravenous administration of CpG-AgNPs effectively targeted atherosclerotic plaques and exhibited potent therapeutic efficacy with excellent biocompatibility. Our study provides valuable insights into CpG-induced macrophage efferocytosis and highlights the potential of CpG-AgNPs as a promising therapeutic strategy for AS.

[Determination of amanita peptide and tryptamine toxins in wild mushrooms by high performance liquid chromatography-tandem mass spectrometry].

The discovery and identification of mushroom toxins has long been an important area in the fields of toxicology and food safety. Mushrooms are widely favored for their culinary and medicinal value; however, the presence of potentially lethal toxins in some species poses a substantial challenge in ensuring their safe consumption. Therefore, the development of a robust and sensitive analytical method is necessary for accurately identifying the risks associated with mushroom consumption. The study of mushroom toxins, which are characterized by their diversity and substantial variations in chemical structures, present a considerable challenge for achieving precise and high-throughput analysis. To address this issue, the present study employed a robust approach combining a solid-phase extraction (SPE) purification technique with high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to establish an analytical method for the detection and quantification of five amatoxins and two tryptamines (psilocybin and bufotenine) present in some mushrooms. Several optimization procedures were undertaken, including optimizing the chromatographic conditions, mass spectrometric parameters, and sample extraction and purification. The procedure involved the extraction of dry mushroom powder with methanol containing 0.3% formic acid, followed by purification using a strong cation exchange cartridge (SCX). The analytes were separated on a T3 chromatographic column (100 mm×2.1 mm, 1.8 µm) using mobile phases of acetonitrile and 5 mmol/L ammonium acetate solution containing 0.1% formic acid. The multiple reaction monitoring (MRM) mode was employed for data acquisition. Amatoxins were quantified using matrix-matched standard calibration curves, whereas isotopic internal standards were used to quantify tryptamine. The results showed that all seven toxins exhibited good linearities (r2>0.99) within the optimized concentration range. The limits of detection (LODs) for bufotenine, psilocybin, and amatoxins were determined as 2.0, 5.0, and 10 µg/kg, respectively, while the limits of quantification (LOQs) were determined as 5.0, 10, and 20 µg/kg, respectively. The LOD and LOQ values further underscore the ability of the method to detect minute quantities of toxins, making it particularly well suited for screening food samples for potential contamination. Using dried shiitake mushroom powder as the matrix, the recoveries of the two tryptamines ranged from 80.6% to 117%, with relative standard deviations (RSDs) ranging from 1.73% to 5.98%, while the recoveries of amatoxins ranged from 71.8% to 115%, with RSDs varying from 2.14% to 9.92% at the three concentration levels. The consistent and satisfactory recoveries of amatoxins and tryptamines demonstrated the ability of this method to accurately quantify the target analytes even in a complex matrix. Comparison with the results of supplementary test method recognized by State Administration for Market Regulation for food (BJS 202008) demonstrated comparable results, indicating no significant differences (p>0.05) in amatoxin contents. The newly developed method is rapid, accurate, precise, meets the required standards, and is suitable for the detection of seven toxins in wild mushrooms. As part of the application of this method, a comprehensive investigation of the distribution of toxins in wild mushrooms from Fujian Province was undertaken. In this study, 59 wild mushroom samples from nine cities were collected in the Fujian province. Species identification was conducted using rDNA-internal transcribed space (rDNA-ITS) molecular barcode technology, which revealed the presence of toxins in the two samples. Notably, one specimen named Amanita fuligineoides contained α-amanitin, ß-amanitin, and phalloidin in quantities of 607, 377, and 69.0 mg/kg, respectively. Additionally, another sample, identified as Tricholomataceae, had a psilocybin concentration of 12.6 mg/kg.

Engineering the Intestinal Lymphatic Transport of Oral Nanoparticles to Educate Macrophages for Cancer Combined Immunotherapy.

The effectiveness of the commonly used therapy is low for treating triple-negative breast cancer (TNBC). Macrophages, accounting for up to 50% of the TNBC tumor mass, are involved in innate and adaptive immunity, which can serve as an effective weapon against TNBC via combined immunotherapy. Here, we engineered mannose and glycocholic acid-modified trimethyl chitosan (MTG) nanoparticles (NPs) encapsulating signal regulatory protein α (SIRPα) siRNA (siSIRPα, a macrophage checkpoint inhibitor) and mucin 1 (MUC1) pDNA (pMUC1, a therapeutic pDNA vaccine) (MTG/siSIRPα/pMUC1 NPs) for in situ educating macrophages via an oral route to exert the cooperative antitumor effects of siSIRPα and pMUC1. Orally delivered MTG-based NPs accumulated in the macrophages in lymph nodes and tumor tissues via the intestinal lymphatic transport pathway, leading to strong cellular immunity responses. Following the transfection of orally administered MTG/siSIRPα/pMUC1 NPs within the same macrophages, siSIRPα strengthened the pMUC1 vaccine-induced systemic cellular immunity, while pMUC1 enhanced siSIRPα-mediated macrophage phagocytosis, M1-phenotype polarization, and tumor microenvironment (TME) remodeling at the tumor sites, thereby inhibiting the growth and metastasis of TNBC. The simultaneous achievements of the mutual promotion of innate and adaptive immunity in the local TME and in the whole body suggested that MTG/siSIRPα/pMUC1 NPs would provide a promising paradigm for the combined immunotherapy of TNBC via oral delivery of genes.

Comprehensive Pan-Cancer Analysis of MTF2 Effects on Human Tumors.

Understanding oncogenic processes and underlying mechanisms to advance research into human tumors is critical for effective treatment. Studies have shown that Metal regulatory transcription factor 2（MTF2) drives malignant progression in liver cancer and glioma. However, no systematic pan-cancer analysis of MTF2 has been performed. Here, we use University of California Santa Cruz, Cancer Genome Atlas , Genotype-Tissue Expression data, Tumor Immune Estimation Resource, and Clinical Proteomic Tumor Analysis Consortium bioinformatics tools to explore differential expression of MTF2 across different tumor types. MTF2 was found to be highly expressed in the cancer lines that were available through the respective databases included in the study, and overexpression of MTF2 may lead to a poor prognosis in tumor patients such as glioblastoma multiforme, brain lower grade glioma, KIPAN, LIHC, adrenocortical carcinoma, etc. We also validated MTF2 mutations in cancer, compared MTF2 methylation levels in normal and primary tumor tissues, analyzed the association of MTF2 with the immune microenvironment, and validated the functional role of MTF2 in glioma U87 and U251 and breast cancer MDA-MB-231 cell lines by cytometry. This also indicates that MTF2 has a promising application prospect in cancer treatment.

Linarin Ameliorates Diabetic Liver Injury by Alleviating Oxidative Stress and Inflammation through the Inhibition of AKR1B1.

AIMS: The study aims to find a new functional additive for diabetic liver injury. BACKGROUND: It is well-established that type 2 diabetes mellitus (T2DM) is a metabolic disease with multiple complications and places a significant health and economic burden on modern society. Linarin is a natural flavonoid isolated from Asteraceae and Lamiaceae, which has beneficial effects in preventing and treating metabolic diseases such as nonalcoholic steatohepatitis and diabetes. OBJECTIVE: We aimed to investigate the pharmacological effect and underlying mechanism of linarin on T2DM-associated liver injury in vivo and in vitro. METHODS: Using a high-glucose and high-palmitic acid-induced hepatocyte injury model and a type 2 diabetic rat model. Following linarin treatment, serum biochemical parameters, liver histology, and lipid profiles of rats were examined. Oxidative stress index and inflammatory response were detected in vivo and in vitro. The expression level of AKR1B1 in rat liver tissues and in vitro cells was detected by western blot and by real-time fluorescent quantitative PCR. RESULTS: The present study found that linarin could prevent oxidative stress and inflammation. In high-fat-fed diabetic rats, linarin administration (15, 30, and 60 mg/kg/day) reduced hepatic lipid accumulation, oxidative stress, and inflammation. Linarin (20 µM) significantly alleviated oxidative stress, inflammation, and apoptosis induced by high glucose combined with palmitic acid in LX-2 cells. Western blotting and overexpression experiments showed that these effects were related to AKR1B1 inhibition in vivo and in vitro. CONCLUSION: This study indicated that linarin could protect against liver injury in T2DM by alleviating oxidative stress and inflammation mediated by AKR1B1 and may be a promising additive for diabetic liver injury therapy.

Cellulose nanocrystal as an enhancing core for antitumor polymeric micelles to overcome biological barriers.

Polymeric micelles are extensively studied nanocarriers to improve the solubility, blood circulation, biodistribution, and adverse effects of chemotherapeutic drugs. However, the antitumor efficacy of polymeric micelles is often restricted due to multiple biological barriers, including blood fluid shear stress (FSS) and limited tumor penetration in vivo. Herein, cellulose nanocrystal (CNC) as a green material with rigidity and rod-shaped structure is developed to be an enhancing core for polymeric micelles to overcome these biological barriers. Doxorubicin (DOX) loaded methoxy poly (ethylene glycol)-block-poly (D, L-lactic acid) (mPEG-PLA, PP) ligated CNC nanoparticles (PPC/DOX NPs) are fabricated via one-pot synthesis. In comparison to the self-assembled DOX loaded mPEG-PLA micelles (PP/DOX NPs), PPC/DOX NPs exhibit remarkable improvements in FSS resistance, cellular internalization, blood circulation, tumor penetration, and antitumor efficacy owing to the unique rigidity and rod-shaped structure of CNC core. Moreover, PPC/DOX NPs present various advantages beyond DOX·HCl and CNC/DOX NPs. The superiority of PPC/DOX NPs in antitumor efficacy reveals the effectiveness of adopting CNC as the enhancing core for polymeric micelles, suggesting that CNC is a promising biomaterial in advancing nanomedicine.

Diffusion kurtosis imaging and MRI-detected extramural venous invasion in rectal cancer: correlation with clinicopathological prognostic factors.

OBJECTIVE: To investigate the prognostic value of the diffusion kurtosis imaging (DKI)-derived parameters D value, K value, diffusion-weighted imaging (DWI) parameter apparent diffusion coefficient (ADC) value, and magnetic resonance imaging (MRI)-detected extramural venous invasion (EMVI) (mrEMVI) in rectal cancer patients. METHODS: Forty patients who underwent MRI for rectal cancer were retrospectively evaluated. DKI-derived parameters D and K were measured using the Medical Imaging Interaction Toolkit. Conventional ADC values were measured from the corresponding DWI images. An experienced radiologist evaluated the mrEMVI status on MR images using the mrEMVI scoring system. An independent sample t-test or analysis of variance was used to analyze and compare the measurement data. The x2 test or Fisher exact test was used for categorical variables. Receiver operating characteristic curves were used to assess the diagnostic performance of these parameters. RESULTS: Among the 40 patients, MRI showed positive EMVI in 15 patients and negative EMVI in 25 patients. Positive mrEMVI status was associated with age, positive circumferential resection margin, pT-stage, lymphovascular invasion (LVI), distant metastasis, and serum carcinoembryonic antigen (CEA) level (P = 0.004-0.036). The dispersion coefficient (D) values and ADC values were significantly higher in the mucinous adenocarcinoma (MC) group than in the common adenocarcinoma (AC) group (P = 0.001), while kurtosis coefficient (K) values were lower in the MC group than in the AC group (P = 0.022). D values were significantly higher in the KRAS-mutated group than in the wild-type group (P < 0.05), whereas K values were lower in the KRAS-mutated group than in the wild-type group (P < 0.05). All three parameters (D, K, and ADC values) showed good diagnostic performance for discriminating MC from AC. Both the D and K values showed certain diagnostic performance for discriminating KRAS mutation. CONCLUSION: DKI-derived parameters, conventional ADC values, and mrEMVI are associated with different histopathological prognostic factors. All DKI-derived parameters and conventional ADC values may distinguish MC from AC. DKI-derived parameters may also be used to discriminate KRAS mutation.

Construction of a Competitive Endogenous RNA Network Related to Exosomes in Diabetic Retinopathy.

BACKGROUND: The competing endogenous RNA (ceRNA) network plays an important role in the occurrence and development of a variety of diseases. This study aimed to construct a ceRNA network related to exosomes in diabetic retinopathy (DR). METHODS: We explored the Gene Expression Omnibus (GEO) database and then analyzed the RNAs of samples to obtain differentially expressed lncRNAs (DELs), miRNAs (DEMs) and mRNAs (DEGs) alongside the progress of DR. Next, Gene Set Enrichment Analysis (GSEA) analysis of DEGs, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of up-DEGs were performed. In addition, a ceRNA network related to exosomes in DR was constructed on the base of DELs, DEMs and DEGs. Finally, the function of the ceRNA network was explored by GO and KEGG enrichment analysis. RESULTS: Through our analysis, 267 DELs (93 up and 174 down), 114 DEMs (64 up and 50 down) and 2368 DEGs (1252 up and 1116 down) were screened. The GSEA analysis results show that these genes were mainly related to cytokine-cytokine receptor interaction, hippo signaling pathway and JAK-STAT signaling pathway. The GO and KEGG results show that these up-DEGs were mainly enriched in viral gene expression, components of ribosomes, mineral absorption, Wntprotein binding, and TGF-ß signaling pathway. Besides, a ceRNA network, including 15 lncRNAs (e.g., C1orf145, FGF14-IT1, and PRNT), 3 miRNAs (miR-10a-5p, miR-1297 and miR-507) and 11 mRNAs (NCOR2, CHAC1 and LIX1L, etc.) was constructed. Those 5 lncRNAs were up-regulated, 1 miRNA was down-regulated and 5 mRNAs were up-regulated in DR, while 10 lncRNAs were downregulated, 2 miRNAs were up-regulated and 6 mRNAs were down-regulated in DR. CONCLUSION: The novel ceRNA network that we constructed will provide new insights into the underlying molecular mechanisms of exosomes in DR.

3D deep learning versus the current methods for predicting tumor invasiveness of lung adenocarcinoma based on high-resolution computed tomography images.

Background: Different pathological subtypes of lung adenocarcinoma lead to different treatment decisions and prognoses, and it is clinically important to distinguish invasive lung adenocarcinoma from preinvasive adenocarcinoma (adenocarcinoma in situ and minimally invasive adenocarcinoma). This study aims to investigate the performance of the deep learning approach based on high-resolution computed tomography (HRCT) images in the classification of tumor invasiveness and compare it with the performances of currently available approaches. Methods: In this study, we used a deep learning approach based on 3D conventional networks to automatically predict the invasiveness of pulmonary nodules. A total of 901 early-stage non-small cell lung cancer patients who underwent surgical treatment at Shanghai Chest Hospital between November 2015 and March 2017 were retrospectively included and randomly assigned to a training set (n=814) or testing set 1 (n=87). We subsequently included 116 patients who underwent surgical treatment and intraoperative frozen section between April 2019 and January 2020 to form testing set 2. We compared the performance of our deep learning approach in predicting tumor invasiveness with that of intraoperative frozen section analysis and human experts (radiologists and surgeons). Results: The deep learning approach yielded an area under the receiver operating characteristic curve (AUC) of 0.946 for distinguishing preinvasive adenocarcinoma from invasive lung adenocarcinoma in the testing set 1, which is significantly higher than the AUCs of human experts (P<0.05). In testing set 2, the deep learning approach distinguished invasive adenocarcinoma from preinvasive adenocarcinoma with an AUC of 0.862, which is higher than that of frozen section analysis (0.755, P=0.043), senior thoracic surgeons (0.720, P=0.006), radiologists (0.766, P>0.05) and junior thoracic surgeons (0.768, P>0.05). Conclusions: We developed a deep learning model that achieved comparable performance to intraoperative frozen section analysis in determining tumor invasiveness. The proposed method may contribute to clinical decisions related to the extent of surgical resection.

Downregulation of TRIM33 Promotes Survival and Epithelial-Mesenchymal Transition in Gastric Cancer.

Among all malignancies worldwide, gastric cancer is the fifth most common cancer with the third highest mortality rate. One of the main reasons for the low survival rate is the recurrence and metastasis that occurs in many patients after surgery. Numerous studies have shown that abnormal TRIM33 expression is associated with the progression of malignant tumors. TRIM33 can function either as a tumor suppressor or tumor promoter in different cancers. Our data showed that TRIM33 was highly expressed in stomach cancer, and in human gastric cancer tissues, low expression of TRIM33 was associated with poor prognosis in patients with gastric cancer. To clarify the function of TRIM33 in survival and epithelial-mesenchymal transition in gastric cancer cells, we investigated the effect of TRIM33 knockdown in several gastric cancer cell lines. Downregulation of TRIM33 in BGC-823 and SGC-7901 cells enhanced the proliferation, colony formation, and migratory ability of these gastric cancer cells. It also promoted epithelial-mesenchymal transition; transfection of cells with siRNA targeting TRIM33 led to the upregulation of vimentin and N-Cadherin expression, and downregulation of E-Cadherin expression. Meanwhile, the transforming growth factor beta pathway was activated: levels of transforming growth factor beta were elevated and the expressions of p-Smad2, Smad2, Smad3, and Smad4 were activated. To confirm the role of TRIM33 in vivo, a xenograft model was established in nude mice. Immunohistochemical analysis identified that the protein levels of TRIM33, p-Smad2, Smad2, Smad3, Smad4, vimentin, and N-Cadherin were increased, and E-Cadherin levels were decreased, in xenograft tumors from the si-TRIM33 group. Taken together, these results suggest that TRIM33 may be a potential marker for the diagnosis and prognosis of gastric cancer. Furthermore, it may also serve as a novel target for gastric cancer treatment.

Excessive activation of HOXB13/PIMREG axis promotes hepatocellular carcinoma progression and drug resistance.

The transcription factor HOXB13 is bound up with the occurrence, progression and drug fast of many kinds of cancer. Nevertheless, the specific molecular mechanism of HOXB13 in hepatocellular carcinoma (HCC) is still unknown. This provides an obstacle to the exploration of HCC treatments targeting HOXB13. This study found that HOXB13 was up-regulated in HCC tissues. HOXB13 enhanced the multiplication and metastasis of HCC cells. It enhanced HCC cell drug and anoikis resistance. The analysis of HCC RNA seq data indicated that the expression of HOXB13 and PIMREG were positively correlated. Luciferase report assay showed that HOXB13 could activate PIMREG promoter transcription. The results of RT-qPCR and western blot showed that HOXB13 regulated the transcription of PIMREG. Western blot proved that high expression of PIMREG participated in DNA damage repair and cell cycle regulation by up-regulating RAD51, BRCA1, CDC25A, CDC25B and CDC25C and down-regulating HIPK2. This led to a significant increase in DNA repair capacity, accelerated cell cycle progression, and insensitive to DNA damage. Down-regulation of PIMREG in Hep3B cells overexpressing HOXB13 attenuated the phenotype induced by HOXB13. Therefore, HOXB13 functioned through PIMREG instead of directly regulating the transcription of RAD51, BRCA1, CDC25A, CDC25B and CDC25C. The same results were obtained in vivo. It was concluded that HOXB13 affected the expression of cell cycle and DNA repair related factors by up-regulating the transcription of PIMREG, thereby promoting the progression of HCC and enhancing the resistance of HCC to chemotherapeutics.