Constructing a personalized prognostic risk model for colorectal cancer using machine learning and multi-omics approach based on epithelial-mesenchymal transition-related genes.

The progression and the metastatic potential of colorectal cancer (CRC) are intricately linked to the epithelial-mesenchymal transition (EMT) process. The present study harnesses the power of machine learning combined with multi-omics data to develop a risk stratification model anchored on EMT-associated genes. The aim is to facilitate personalized prognostic assessments in CRC. We utilized publicly accessible gene expression datasets to pinpoint EMT-associated genes, employing a CoxBoost algorithm to sift through these genes for prognostic significance. The resultant model, predicated on gene expression levels, underwent rigorous independent validation across various datasets. Our model demonstrated a robust capacity to segregate CRC patients into distinct high- and low-risk categories, each correlating with markedly different survival probabilities. Notably, the risk score emerged as an independent prognostic indicator for CRC. High-risk patients were characterized by an immunosuppressive tumor milieu and a heightened responsiveness to certain chemotherapeutic agents, underlining the model's potential in steering tailored oncological therapies. Moreover, our research unearthed a putative repressive interaction between the long non-coding RNA PVT1 and the EMT-associated genes TIMP1 and MMP1, offering new insights into the molecular intricacies of CRC. In essence, our research introduces a sophisticated risk model, leveraging machine learning and multi-omics insights, which accurately prognosticates outcomes for CRC patients, paving the way for more individualized and effective oncological treatment paradigms.

An internal filtration effect-based "off-on" probe for fluorescent and visual sensing of formaldehyde.

Formaldehyde (FA) sensing in children's toys and water has great application prospects in the protection of home safety and the ecological environment. However, there has been no report heretofore addressing FA detection in children's toys. In this work, a fluorescent (FL) whitening agent (FWA), potassium dichromate, and sulfuric acid were proposed as an "off-on" probe (FPD) for FA sensing via FL and visual FL (VFL) methods. The FL emission of the FWA at 435 nm was quenched by Cr2O72- because of the internal filtration effect. The effect was interrupted after the addition of FA because Cr2O72- was reduced to Cr3+, accompanying the recovery of the FL emission of the FWA. The detection limit of FPD for FA via FL and VFL approaches was 2.03 and 85.5 µg L-1, respectively. The proposed probe was successfully utilized for FA detection in crawling mats and building blocks as well as environmental water (verified by the UV method), indicating good adaptability. The FPD-based FL method might be a potential approach for FA detection due to the merits of high selectivity, anti-interference ability, and stability.

Fluorescent and visual sensing of sodium dodecylbenzene sulfonate with an aminosilane self-condensation promoting and electrostatic attraction effect-based ratiometric probe.

BACKGROUND: Increasing attention has been paid to sodium dodecylbenzene sulfonate (SDBS) detection because it could cause damage to human body and environmental water. For example, SDBS must not be detected on tableware surface according to national standard of China (GB 14934-2016). However, there is no report heretofore addressing SDBS sensing on surfaces. More importantly, the interferents often affect the sensing performance of analytical approaches. Hence, there is an urgent need to establish a method with good anti-interference ability for SDBS detection both on tableware surfaces and in water. RESULTS: Inspired by a finding that SDBS could cause the generation of white turbidity in (3-aminopropyl)trimethoxysilane (APTMS, an aminosilane) aqueous solution, APTMS modified Mn doped ZnS quantum dots (QDs) and fluorescent (FL) whitening agent (FWA) were constructed as a ratiometric probe for FL and visual sensing of SDBS. The modified QDs aggregated and settled in presence of SDBS, which was likely to be connected to the stimulatory effect of SDBS on the APTMS self-condensation and the electrostatic attraction. The FL emission from the QDs at 605 nm then decreased dramatically, whereas that at 425 nm was virtually constant owing to FWA. SDBS sensing could be achieved by calculating the ratio change of their FL intensities. The detection limits of FL and visual methods were found to be 0.011 and 10 µg/L, respectively, making it one of the most sensitive approaches in literature. Finally, it was successfully utilized for SDBS detection on tableware surfaces and in water. SIGNIFICANCE: Herein, the specific interaction between SDBS and APTMS was reported and the reaction mechanisms were explored for the first time. The proposed probe based on the effect described above provided a promising potential for SDBS analysis owing to high sensitivity, selectivity, anti-interference ability, and stability (in 20 days).

Halogen ion modified Ag NPs for ultrasensitive SERS detection of nitroaromatic explosives.

Trace explosive detection has become one of the hottest topics in scientific communities because homeland security is one of the top priorities for countries all around the world. In this work, Ag NPs prepared with different reducing reagents were modified with various halogen ions for the SERS detection of nitroaromatic explosives (2,4-DNT and 2,4,6-TNT). It was proposed that halogen ions probably replaced the surface adsorbates on Ag NPs, i.e., citrate ions, and gave surface access to target analytes, which in turn enhanced the SERS signal. The LOD values for TNT and 2,4-DNT were found to be only 2 femtomoles. Given its facile and the highly sensitive process, the method that we demonstrated can serve as a promising analytical technology for the ultrasensitive SERS detection of nitroaromatic explosives.

Pachymic Acid Ameliorates Pulmonary Hypertension by Regulating Nrf2-Keap1-ARE Pathway.

OBJECTIVE: Pulmonary hypertension (PH) is a severe pulmonary vascular disease that eventually leads to right ventricular failure and death. The purpose of this study was to investigate the mechanism by which pachymic acid (PA) pretreatment affects PH and pulmonary vascular remodeling in rats. METHODS: PH was induced via hypoxia exposure and administration of PA (5 mg/kg per day) in male Sprague-Dawley rats. Hemodynamic parameters were measured using a right ventricular floating catheter and pulmonary vascular morphometry was measured by hematoxylin-eosin (HE), α-SMA and Masson staining. MTT assays and EdU staining were used to detect cell proliferation, and apoptosis was analyzed by TUNEL staining. Western blotting and immunohistochemistry were used to detect the expression of proteins related to the Nrf2-Keap1-ARE pathway. RESULTS: PA significantly alleviated hypoxic PH and reversed right ventricular hypertrophy and pulmonary vascular remodeling. In addition, PA effectively inhibited proliferation and promoted apoptosis in hypoxia-induced pulmonary artery smooth muscle cells (PASMCs). Moreover, PA pretreatment inhibited the expression of peroxy-related factor (MDA) and promoted the expression of antioxidant-related factors (GSH-PX and SOD). Furthermore, hypoxia inhibited the Nrf2-Keap1-ARE signaling pathway, while PA effectively activated this pathway. Most importantly, addition of the Nrf2 inhibitor ML385 reversed the inhibitory effects of PA on ROS generation, proliferation, and apoptosis tolerance in hypoxia-induced PASMCs. CONCLUSION: Our study suggests that PA may reverse PH by regulating the Nrf2-Keap1-ARE signaling pathway.

Highly sensitive SERS detection of residual nitrofurantoin and 1-amino-hydantoin in aquatic products and feeds.

Nitrofurantoin (NFT), a typical highly effective nitrofuran antibiotic drug, has been prohibited but still widely found in animal food products. It can be metabolized in animals to form 1-amino-hydantoin (AHD) that can then form stable and toxic metabolite-protein adducts. Hence, the detection of NFT and AHD in aquatic products and feeds is very important. However, there are limited reports concerning NFT detection and none about AHD by using surface-enhanced Raman spectroscopy (SERS) method. Herein, potassium bromide (KBr) decorated silver (Ag) nanoparticles (Ag-BrNPs)-based SERS approach was proposed for NFT and AHD detection. The limit of detection (LOD) for NFT was 1 µg/L. The detection of NFT residues in sea cucumber and fish feeds was also realized with the LOD of 1 and 50 ng/g, respectively. More importantly, the sensing of AHD was easily realized with the SERS approach for the first time. After the derivatization with 2-nitrobenzaldehyde (2-NBA), Ag-BrNPs were also successfully utilized for AHD detection in sea cucumber with the LOD of 5 ng/g.

Multifunctional Flexible SERS Sensor on a Fixate Gel Pad: Capturing, Derivation, and Selective Picogram Indirect Detection of Explosive 2,2',4,4',6,6'-Hexanitrostilbene.

2,2',4,4',6,6'-Hexanitrostilbene (HNS) is an explosive with better explosion performance than the well-known 2,4,6-trinitrotoluene (TNT). Surprisingly, unlike other nitroaromatic explosives, there are limited reports regarding the detection of the HNS, let alone sensing reports on surface residues. In this work, a multifunctional flexible SERS sensor was proposed for the indirect detection of HNS based on the transparent fixate gel pads. The sticky and flexible gel pad can effectively collect any HNS surface residues. The inherent amine groups within the gel pad of which the main ingredient is polyurethane can react with HNS to form the orange Meisenheimer-alike complex. The modification of Ag NPs with halide ions was screened for the best SERS performance. KI-modified-citrate-reduced Ag NPs showed selective but enormous SERS enhancement for the HNS derivative. The detection of HNS in the solution phase was explored, and a linear range of 0.01-25 ppm was achieved. The lowest detectable amount (LDA) of HNS was found to be 50 pg, making it one of the most sensitive methods in literature. It was successfully utilized for the HNS residues sensing on fingerprints and bags with LDAs of 5 and 200 ng, respectively. In addition, other explosives including TATB, LLM-105, RDX, HMX, FOX-7, and TNT were also examined to assess the selectivity of the fixate. It was found that the fixate showed excellent selectivity for HNS.

From children's toy to versatile sensor: One-step doping of Play-Doh with primary amino group for explosive detection both on surfaces and in solution.

2,4,6-trinitrotoluene (TNT) sensing on surfaces and in solution is an important issue in sensor fabrication for homeland security and environmental protection. Herein, Play-Doh, a modeling material popular for kids, was proposed as a versatile sensor for on-site fluorescent (FL), visual FL (VFL), and colorimetric detection of TNT both on surfaces and in solution after being doped with -NH2 through a one-step approach. Play-Doh exhibits FL emission due to the main ingredient of flour. After -NH2 doping, amino-Play-Doh (APD) was utilized to construct a FL sensor based on FL resonance energy transfer and inner filter effect for TNT detection. The advantage of APD was that no additional fluorophore was needed compared with the traditional sensors for FL and VFL analysis. The orange complex visible to the naked eye was also recorded for smartphone-based colorimetric detection of TNT. In both cases, the APD demonstrated good analytical performance for TNT. Finally, APD was successfully utilized for TNT sensing on fingerprints, luggage, and in environmental water samples, respectively. Play-Doh might be a potential sensor for future on-site detection of TNT owing to the merits of being cost-effective and versatile.

Screening for malachite green contamination on live fish skin with chewing gum based viscoelastic SERS sensor.

Malachite green (MG), a prohibited but still found antimicrobial in aquafarm and during live fish shipping, is a hot target in food safety screening. Herein, a novel chewing gum based flexible SERS (G-SERS) sensor was proposed for rapid sampling and detection of MG on live fish skin. The whole analysis takes <5 min, while the limit of detection for MG is 0.73 pg. Different from other reports, MG contaminated live fish was monitored daily with the G-SERS sensor, during which the fish was firstly raised in 0.5 ppm MG solution for one day, followed by freshwater for a week. It was found that the SERS signal of residue MG on fish skin could still be seen even on the sixth day, roughly the sale cycle of live fish in a marketplace. Furthermore, the method was also applied for MG screening on the skin of fish purchased from a supermarket and a local street marketplace. MG was found on some fishes from the latter but not from the former, which was cross-validated by LC-MS, suggesting MG risks still exist in smaller marketplaces. This work demonstrated the feasibility of using the flexible SERS sensor for onsite food safety screening.