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Mashup Score: 0Single-Cell Untargeted Lipidomics Using Liquid Chromatography and Data-Dependent Acquisition after Live Cell Selection - 14 day(s) ago
We report the development and validation of an untargeted single-cell lipidomics method based on microflow chromatography coupled to a data-dependent mass spectrometry method for fragmentation-based identification of lipids. Given the absence of single-cell lipid standards, we show how the methodology should be optimized and validated using a dilute cell extract. The methodology is applied to dilute pancreatic cancer and macrophage cell extracts and standards to demonstrate the sensitivity requirements for confident assignment of lipids and classification of the cell type at the single-cell level. The method is then coupled to a system that can provide automated sampling of live, single cells into capillaries under microscope observation. This workflow retains the spatial information and morphology of cells during sampling and highlights the heterogeneity in lipid profiles observed at the single-cell level. The workflow is applied to show changes in single-cell lipid profiles as a resp
Source: pubs.acs.orgCategories: General Medicine News, Hem/OncsTweet
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Mashup Score: 85Analysis of Microplastics in Human Feces Reveals a Correlation between Fecal Microplastics and Inflammatory Bowel Disease Status - 19 day(s) ago
Human ingestion of microplastics (MPs) is inevitable due to the ubiquity of MPs in various foods and drinking water. Whether the ingestion of MPs poses a substantial risk to human health is far from understood. Here, by analyzing the characteristics of MPs in the feces of patients with inflammatory bowel disease (IBD) and healthy people, for the first time, we found that the fecal MP concentration in IBD patients (41.8 items/g dm) was significantly higher than that in healthy people (28.0 items/g dm). In total, 15 types of MPs were detected in feces, with poly(ethylene terephthalate) (22.3–34.0%) and polyamide (8.9–12.4%) being dominant, and their primary shapes were sheets and fibers, respectively. We present evidence indicating that a positive correlation exists between the concentration of fecal MPs and the severity of IBD. Combining a questionnaire survey and the characteristics of fecal MPs, we conclude that the plastic packaging of drinking water and food and dust exposure are im
Source: pubs.acs.orgCategories: General Medicine News, Hem/OncsTweet
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Mashup Score: 0
Small molecules that induce protein degradation hold the potential to overcome several limitations of the currently available inhibitors. Monovalent or molecular glue degraders, in particular, enable the benefits of protein degradation without the disadvantages of high molecular weight and the resulting challenge in drug development that are associated with bivalent molecules like Proteolysis Targeting Chimeras. One key challenge in designing monovalent degraders is how to build in the degrader activity─how can we convert an inhibitor into a degrader? If degradation activity requires very specific molecular features, it will be difficult to find new degraders and challenging to optimize those degraders toward drugs. Herein, we demonstrate that an unexpectedly wide range of modifications to the degradation-inducing group of the cyclin K degrader CR8 are tolerated, including both aromatic and nonaromatic groups. We used these findings to convert the pan-CDK inhibitors dinaciclib and AT-7
Source: pubs.acs.orgCategories: General Medicine News, Hem/OncsTweet
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Mashup Score: 1Iron Oxide Nanoparticles Inhibit Tumor Progression and Suppress Lung Metastases in Mouse Models of Breast Cancer - 1 month(s) ago
Systemic exposure to starch-coated iron oxide nanoparticles (IONPs) can stimulate antitumor T cell responses, even when little IONP is retained within the tumor. Here, we demonstrate in mouse models of metastatic breast cancer that IONPs can alter the host immune landscape, leading to systemic immune-mediated disease suppression. We report that a single intravenous injection of IONPs can inhibit primary tumor growth, suppress metastases, and extend survival. Gene expression analysis revealed the activation of Toll-like receptor (TLR) pathways involving signaling via Toll/Interleukin-1 receptor domain-containing adaptor-inducing IFN-β (TRIF), a TLR pathway adaptor protein. Requisite participation of TRIF in suppressing tumor progression was demonstrated with histopathologic evidence of upregulated IFN-regulatory factor 3 (IRF3), a downstream protein, and confirmed in a TRIF knockout syngeneic mouse model of metastatic breast cancer. Neither starch-coated polystyrene nanoparticles lackin
Source: pubs.acs.orgCategories: General Medicine News, Onc News and JournalsTweet
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Mashup Score: 46
Tap water nano/microplastics (NMPs) escaping from centralized water treatment systems are of increasing global concern, because they pose potential health risk to humans via water consumption. Drinking boiled water, an ancient tradition in some Asian countries, is supposedly beneficial for human health, as boiling can remove some chemicals and most biological substances. However, it remains unclear whether boiling is effective in removing NMPs in tap water. Herein we present evidence that polystyrene, polyethylene, and polypropylene NMPs can coprecipitate with calcium carbonate (CaCO3) incrustants in tap water upon boiling. Boiling hard water (>120 mg L–1 of CaCO3) can remove at least 80% of polystyrene, polyethylene, and polypropylene NMPs size between 0.1 and 150 μm. Elevated temperatures promote CaCO3 nucleation on NMPs, resulting in the encapsulation and aggregation of NMPs within CaCO3 incrustants. This simple boiling-water strategy can “decontaminate” NMPs from household tap wate
Source: pubs.acs.orgCategories: General Medicine News, General HCPsTweet
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Mashup Score: 23Inversion of the Warburg Effect: Unraveling the Metabolic Nexus between Obesity and Cancer - 2 month(s) ago
Obesity is a well-established risk factor for cancer, significantly impacting both cancer incidence and mortality. However, the intricate molecular mechanisms connecting adipose tissue to cancer cell metabolism are not fully understood. This Review explores the historical context of tumor energy metabolism research, tracing its origins to Otto Warburg’s pioneering work in 1920. Warburg’s discovery of the “Warburg effect”, wherein cancer cells prefer anaerobic glycolysis even in the presence of oxygen, laid the foundation for understanding cancer metabolism. Building upon this foundation, the “reverse Warburg effect” emerged in 2009, elucidating the role of aerobic glycolysis in cancer-associated fibroblasts (CAFs) and its contribution to lactate accumulation in the tumor microenvironment, subsequently serving as a metabolic substrate for cancer cells. In contrast, within high-adiposity contexts, cancer cells exhibit a unique metabolic shift termed the “inversion of the Warburg effect”.
Source: pubs.acs.orgCategories: General Medicine News, General HCPsTweet
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Mashup Score: 8Activity of Gut-Derived Nisin-like Lantibiotics against Human Gut Pathogens and Commensals - 3 month(s) ago
Recent advances in sequencing techniques unveiled the vast potential of ribosomally synthesized and post-translationally modified peptides (RiPPs) encoded in microbiomes. Class I lantibiotics such as nisin A, widely used as a food preservative, have been investigated for their efficacy in killing pathogens. However, the impact of nisin and nisin-like class I lantibiotics on commensal bacteria residing in the human gut remains unclear. Here, we report six gut-derived class I lantibiotics that are close homologues of nisin, four of which are novel. We applied an improved lantibiotic expression platform to produce and purify these lantibiotics for antimicrobial assays. We determined their minimal inhibitory concentration (MIC) against both Gram-positive human pathogens and gut commensals and profiled the lantibiotic resistance genes in these pathogens and commensals. Structure–activity relationship (SAR) studies with analogs revealed key regions and residues that impact their antimicrobia
Source: pubs.acs.orgCategories: General Medicine News, General HCPsTweet
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Mashup Score: 8Activity of Gut-Derived Nisin-like Lantibiotics against Human Gut Pathogens and Commensals - 3 month(s) ago
Recent advances in sequencing techniques unveiled the vast potential of ribosomally synthesized and post-translationally modified peptides (RiPPs) encoded in microbiomes. Class I lantibiotics such as nisin A, widely used as a food preservative, have been investigated for their efficacy in killing pathogens. However, the impact of nisin and nisin-like class I lantibiotics on commensal bacteria residing in the human gut remains unclear. Here, we report six gut-derived class I lantibiotics that are close homologues of nisin, four of which are novel. We applied an improved lantibiotic expression platform to produce and purify these lantibiotics for antimicrobial assays. We determined their minimal inhibitory concentration (MIC) against both Gram-positive human pathogens and gut commensals and profiled the lantibiotic resistance genes in these pathogens and commensals. Structure–activity relationship (SAR) studies with analogs revealed key regions and residues that impact their antimicrobia
Source: pubs.acs.orgCategories: General Medicine News, General HCPsTweet
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Mashup Score: 5A Coumarin-Based Array for the Discrimination of Amyloids - 3 month(s) ago
Self-assembly of misfolded proteins can lead to the formation of amyloids, which are implicated in the onset of many pathologies including Alzheimer’s disease and Parkinson’s disease. The facile detection and discrimination of different amyloids are crucial for early diagnosis of amyloid-related pathologies. Here, we report the development of a fluorescent coumarin-based two-sensor array that is able to correctly discriminate between four different amyloids implicated in amyloid-related pathologies with 100% classification. The array was also applied to mouse models of Alzheimer’s disease and was able to discriminate between samples from mice corresponding to early (6 months) and advanced (12 months) stages of Alzheimer’s disease. Finally, the flexibility of the array was assessed by expanding the analytes to include functional amyloids. The same two-sensor array was able to correctly discriminate between eight different disease-associated and functional amyloids with 100% classificati
Source: pubs.acs.orgCategories: General Medicine News, NeurologyTweet
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Mashup Score: 5
Exosomes play an important role in the spread of viral infections and immune escape. However, the exact ability and mechanisms by which exosomes produced during viral infections (vExos) infect host cells are still not fully understood. In this study, we developed a dual-color exosome labeling strategy that simultaneously labels the external and internal structures of exosomes with quantum dots to enable in situ monitoring of the transport process of vExos in live cells using the single-particle tracking technique. Our finding revealed that vExos contains the complete influenza A virus (IAV) genome and viral ribonucleoprotein complexes (vRNPs) proteins but lacks viral envelope proteins. Notably, these vExos have the ability to infect cells and produce progeny viruses. We also found that vExos are transported in three stages, slow–fast–slow, and move to the perinuclear region via microfilaments and microtubules. About 30% of internalized vExos shed the external membrane and release the i
Source: pubs.acs.orgCategories: General Medicine News, Infectious DiseaseTweet
Single-Cell Untargeted Lipidomics Using Liquid Chromatography and Data-Dependent Acquisition after Live Cell Selection https://t.co/l8jw6Ua0HL