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A major function of the DNA damage responses (DDRs) that act during the replicative phase of the cell cycle is to inhibit initiation and elongation of DNA replication. It has been shown that DNA replication of the polyomavirus, SV40, is inhibited and its replication fork is slowed by cellular DDR responses. The inhibition of SV40 DNA replication is associated with enhanced DDR kinase phosphorylation of SV40 Large T-antigen (LT), the viral DNA helicase. Mass spectroscopy was used to identify a novel highly conserved DDR kinase site, T518, on LT. In cell-based assays expression of a phosphomimetic form of LT at T518 (T518D) resulted in dramatically decreased levels of SV40 DNA replication, but LT-dependent transcriptional activation was unaffected. Purified WT and LT T518D were analyzed in vitro. In concordance with the cell-based data, reactions using SV40 LT-T518D, but not T518A, showed dramatic inhibition of SV40 DNA replication. A myriad of LT protein-protein interactions and LT's biochemical functions were unaffected by the LT T518D mutation; however, LT's DNA helicase activity was dramatically decreased on long, but not very short, DNA templates. These results suggest that DDR phosphorylation at T518 inhibits SV40 DNA replication by suppressing LT helicase activity.
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Mitochondrial transcripts in Trypanosoma brucei require extensive uridine insertion/deletion RNA editing to generate translatable open reading frames. The RNA editing substrate binding complex (RESC) serves as the scaffold that coordinates the protein-protein and protein-RNA interactions during editing. RESC broadly contains two modules termed the guide RNA binding complex (GRBC) and the RNA editing mediator complex (REMC), as well as organizer proteins. How the protein and RNA components of RESC dynamically interact to facilitate editing is not well understood. Here, we examine the roles of organizer proteins, RESC8 and RESC14, in facilitating RESC dynamics. High-throughput sequencing of editing intermediates reveals an overlapping RESC8 and RESC14 function during editing progression across multiple transcripts. Blue native PAGE analysis demonstrates that RESC14 is essential for incorporation of RESC8 into a large RNA-containing complex, while RESC8 is important in recruiting a smaller ribonucleoprotein complex (RNP) to this large complex. Proximity labeling shows that RESC14 is important for stable RESC protein-protein interactions, as well as RESC-RECC associations. Together, our data support a model in which RESC14 is necessary for assembly of editing competent RESC through recruitment of an RNP containing RESC8, GRBC and gRNA to REMC and mRNA.
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Trypanosoma brucei occupies distinct niches throughout its life cycle, within both the mammalian and tsetse fly hosts. The immunological and biochemical complexity and variability of each of these environments require a reshaping of the protein landscape of the parasite both to evade surveillance and face changing metabolic demands. In kinetoplastid protozoa, including T. brucei, posttranscriptional control mechanisms are the primary means of gene regulation, and these are often mediated by RNA-binding proteins. DRBD18 is a T. brucei RNA-binding protein that reportedly interacts with ribosomal proteins and translation factors. Here, we tested a role for DRBD18 in translational control. We validate the DRBD18 interaction with translating ribosomes and the translation initiation factor, eIF3a. We further show that DRBD18 depletion by RNA interference leads to altered polysomal profiles with a specific depletion of heavy polysomes. Ribosome profiling analysis reveals that 101 transcripts change in translational efficiency (TE) upon DRBD18 depletion: 41 exhibit decreased TE and 60 exhibit increased TE. A further 66 transcripts are buffered, that is, changes in transcript abundance are compensated by changes in TE such that the total translational output is expected not to change. In DRBD18-depleted cells, a set of transcripts that codes for procyclic form-specific proteins is translationally repressed while, conversely, transcripts that code for bloodstream form- and metacyclic form-specific proteins are translationally enhanced. RNA immunoprecipitation/qRT-PCR indicates that DRBD18 associates with members of both repressed and enhanced cohorts. These data suggest that DRBD18 contributes to the maintenance of the procyclic state through both positive and negative translational control of specific mRNAs.
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Trypanosoma brucei brucei , Animais , Trypanosoma brucei brucei/genética , Imunoprecipitação , Reação em Cadeia da Polimerase , Polirribossomos/genética , RNA , Proteínas de Protozoários/genética , MamíferosRESUMO
AIMS: Pancreatic ductal adenocarcinoma (PDAC) is often intrinsically-resistant to standard-of-care chemotherapies such as gemcitabine. Acquired gemcitabine resistance (GemR) can arise from treatment of initially-sensitive tumors, and chemotherapy can increase tumor aggressiveness. We investigated the molecular mechanisms of chemoresistance and chemotherapy-driven tumor aggressiveness, which are understood incompletely. METHODS: Differential proteomic analysis was employed to investigate chemotherapy-driven chemoresistance drivers and responses of PDAC cells and patient-derived tumor xenografts (PDX) having different chemosensitivities. We also investigated the prognostic value of FGFR1 expression in the efficacy of selective pan-FGFR inhibitor (FGFRi)-gemcitabine combinations. RESULTS: Quantitative proteomic analysis of a highly-GemR cell line revealed fibroblast growth factor receptor 1 (FGFR1) as the highest-expressed receptor tyrosine kinase. FGFR1 knockdown or FGFRi co-treatment enhanced gemcitabine efficacy and decreased GemR marker expression, implicating FGFR1 in augmentation of GemR. FGFRi treatment reduced PDX tumor progression and prolonged survival significantly, even in highly-resistant tumors in which neither single-agent showed efficacy. Gemcitabine exacerbated aggressiveness of highly-GemR tumors, based upon proliferation and metastatic markers. Combining FGFRi with gemcitabine or gemcitabine+nab-paclitaxel reversed tumor aggressiveness and progression, and prolonged survival significantly. In multiple PDAC PDXs, FGFR1 expression correlated with intrinsic tumor gemcitabine sensitivity. CONCLUSION: FGFR1 drives chemoresistance and tumor aggressiveness, which FGFRi can reverse.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/genética , Linhagem Celular Tumoral , Proliferação de Células , Desoxicitidina/farmacologia , Desoxicitidina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Gencitabina , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Proteômica , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/uso terapêuticoRESUMO
The sensitivity of LC-MS in quantifying target proteins in plasma/tissues is significantly hindered by coeluted matrix interferences. While antibody-based immuno-enrichment effectively reduces interferences, developing and optimizing antibodies are often time-consuming and costly. Here, by leveraging the orthogonal separation capability of Field Asymmetric Ion Mobility Spectrometry (FAIMS), we developed a FAIMS/differential-compensation-voltage (FAIMS/dCV) method for antibody-free, robust, and ultrasensitive quantification of target proteins directly from plasma/tissue digests. By comparing the intensity-CV profiles of the target vs coeluted endogenous interferences, the FAIMS/dCV approach identifies the optimal CV for quantification of each target protein, thus maximizing the signal-to-noise ratio (S/N). Compared to quantification without FAIMS, this technique dramatically reduces endogenous interferences, showing a median improvement of the S/N by 14.8-fold for the quantification of 17 representative protein drugs and biomarkers in plasma or tissues and a 5.2-fold median increase in S/N over conventional FAIMS approach, which uses the peak CV of each target. We also discovered that the established CV parameters remain consistent over months and are matrix-independent, affirming the robustness of the developed FAIMS/dCV method and the transferability of the method across matrices. The developed method was successfully demonstrated in three applications: the quantification of monoclonal antibodies with subng/mL LOQ in plasma, an investigation of the time courses of evolocumab and its target PCSK9 in a preclinical setting, and a clinical investigation of low abundance obesity-related biomarkers. This innovative and easy-to-use method has extensive potential in clinical and pharmaceutical research, particularly where sensitive and high-throughput quantification of protein drugs and biomarkers is required.
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Biomarcadores , Biomarcadores/análise , Biomarcadores/sangue , Animais , Humanos , Espectrometria de Mobilidade Iônica/métodos , Cromatografia Líquida/métodos , Proteínas/análise , Espectrometria de Massas/métodos , Camundongos , Preparações Farmacêuticas/análise , Preparações Farmacêuticas/químicaRESUMO
We believe this to be a new superposition twisted Hermite-Gaussian Schell-model (STHGSM) beam hat is proposed. Analytic formulas for the intensity distribution and propagation factor of the STHGSM beam in non-Kolmogorov turbulence are derived by utilizing the generalized Huygens-Fresnel principle (HFP) and the Wigner function. The evolution characteristics of STHGSM beams propagating are numerically calculated and analyzed. Our findings indicate that the light intensity of the STHGSM beam gradually undergoes splitting and rotation around the axis during propagation through non-Kolmogorov turbulence, eventually evolving into a diagonal lobe shape at a certain distance of transmission. The anti-turbulence capability of the beam strengthens with higher beam order or twist factor values.
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The study on structure-property relationship has been a significant focus in the field of organic molecular luminescence. In the present work, three chiral binaphthyl-based triphenylethylene (HTPE) derivatives were prepared through condensation reactions. Despite their similar structures, these compounds exhibited distinct luminescent properties. Diphenylmethane-derived HTPE displayed dual-state emissions, characterized by dual-wavelength emissions which were insensitive to the polarity of solvents. The dual emissions in solution state could be attributed to the different locally excited (LE) excitons. However, upon aggregation, two stable conformers were generated, probably leading to different emission peaks. In contrast, dibenzocycloheptadiene-derived HTPE aggregates showed only a single emission peak. Surprisingly, fluorene-derived HTPE exhibited obvious luminescence in neither solution nor aggregate states due to inherent π-π interactions. These conclusions were substantiated by X-ray analysis, spectroscopic analysis, and theory calculations. Application studies demonstrated that fluorescence on/off switches could be achieved through exposure to acetone. More importantly, trace amounts of acetone could be detected using luminescent materials in both organic and aqueous phases with a detection limit of 0.08 %. Thus, this work not only presents a strategy for designing chiral triphenylethylene fluorophores but also provides valuable information for dual wavelength emissions resulting from two stable conformations.
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Despite the high prevalence and significant health burden of obstructive sleep apnea (OSA), its underlying pathophysiology remains incompletely understood. This comprehensive review explores the emerging connection between vitamin D deficiency and OSA, discusses potential mechanisms underlying this association, and explores the therapeutic implications of these findings. Recent research has consistently highlighted the high incidence of vitamin D deficiency among patients with OSA, which often occurs independently of geographical location. This suggests that factors beyond lack of sunlight exposure may be involved. This review also discusses how reduced vitamin D may be associated with more severe manifestations of OSA. In addition, it explores the potentiality of using vitamin D supplements as a therapeutic strategy for OSA, noting that some studies have found improvements in sleep quality and a reduction in OSA severity. Potential mechanisms are proposed, including the role of vitamin D deficiency in promoting inflammation, oxidative stress, hypoxia, impairing immune function, muscle function, and gene polymorphism of vitamin D receptors, all of which could contribute to the pathogenesis of obstructive sleep apnea. The paper underscores the need for future research to validate these observations, to determine optimal vitamin D supplementation dosage and duration, to explore potential side effects and risks, and to investigate potential interactions with other treatments.
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BACKGROUND AND AIM: The study aims to evaluate the feasibility of body mass index (BMI)-based individualized small bowel preparation for computed tomography enterography (CTE). METHODS: In this prospective randomized controlled study, patients undergoing CTE were randomly assigned to the individualized group or standardized group. Those in individualized group were given different volumes of mannitol solution based on BMI (1000 mL for patients with BMI < 18.5 kg/m2, 1500 mL for patients with 18.5 kg/m2 ≤ BMI < 25 kg/m2 and 2000 mL for patients with BMI ≥ 25 kg/m2) while patients in the standardized group were all asked to consume 1500-mL mannitol solution. CTE images were reviewed by two experienced radiologists blindly. Each segment of the small bowel was assessed for small bowel image quality and disease detection rates. Patients were invited to record a diary regarding adverse events and acceptance. RESULTS: A total of 203 patients were enrolled and randomly divided into two groups. For patients with BMI < 18.5 kg/m2, 1000-mL mannitol solution permitted a significantly lower rate of flatulence (P = 0.045) and defecating frequency (P = 0.011) as well as higher acceptance score (P = 0.015), but did not affect bowel image quality and diseases detection compared with conventional dosage. For patients with BMI ≥ 25 kg/m2, 2000-mL mannitol solution provided better overall image quality (P = 0.033) but comparable rates of adverse events and patients' acceptance compared with conventional dosage. CONCLUSIONS: Individualized bowel preparation could achieve both satisfactory image quality and patients' acceptance thus might be an acceptable alternative in CTE.
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Índice de Massa Corporal , Intestino Delgado , Manitol , Tomografia Computadorizada por Raios X , Humanos , Feminino , Masculino , Estudos Prospectivos , Pessoa de Meia-Idade , Manitol/administração & dosagem , Manitol/efeitos adversos , Tomografia Computadorizada por Raios X/métodos , Intestino Delgado/diagnóstico por imagem , Adulto , Idoso , Estudos de Viabilidade , Catárticos/administração & dosagem , Catárticos/efeitos adversos , Medicina de PrecisãoRESUMO
Pancreatic adenocarcinoma (PDAC) is highly refractory to treatment. Standard-of-care gemcitabine (Gem) provides only modest survival benefits, and development of Gem resistance (GemR) compromises its efficacy. Highly GemR clones of Gem-sensitive MIAPaCa-2 cells were developed to investigate the molecular mechanisms of GemR and implemented global quantitative differential proteomics analysis with a comprehensive, reproducible ion-current-based MS1 workflow to quantify â¼6000 proteins in all samples. In GemR clone MIA-GR8, cellular metabolism, proliferation, migration, and 'drug response' mechanisms were the predominant biological processes altered, consistent with cell phenotypic alterations in cell cycle and motility. S100 calcium binding protein A4 was the most downregulated protein, as were proteins associated with glycolytic and oxidative energy production. Both responses would reduce tumor proliferation. Upregulation of mesenchymal markers was prominent, and cellular invasiveness increased. Key enzymes in Gem metabolism pathways were altered such that intracellular utilization of Gem would decrease. Ribonucleoside-diphosphate reductase large subunit was the most elevated Gem metabolizing protein, supporting its critical role in GemR. Lower Ribonucleoside-diphosphate reductase large subunit expression is associated with better clinical outcomes in PDAC, and its downregulation paralleled reduced MIAPaCa-2 proliferation and migration and increased Gem sensitivity. Temporal protein-level Gem responses of MIAPaCa-2 versus GemR cell lines (intrinsically GemR PANC-1 and acquired GemR MIA-GR8) implicate adaptive changes in cellular response systems for cell proliferation and drug transport and metabolism, which reduce cytotoxic Gem metabolites, in DNA repair, and additional responses, as key contributors to the complexity of GemR in PDAC. These findings additionally suggest targetable therapeutic vulnerabilities for GemR PDAC patients.
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Adenocarcinoma , Neoplasias Pancreáticas , Ribonucleosídeos , Humanos , Linhagem Celular Tumoral , Difosfatos/metabolismo , Difosfatos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Pancreáticas/metabolismo , Proteômica , Ribonucleosídeos/uso terapêutico , Proteína A4 de Ligação a Cálcio da Família S100 , Gencitabina , Neoplasias PancreáticasRESUMO
Following the highly successful Chinese American Society for Mass Spectrometry (CASMS) conferences in the previous 2 years, the 3rd CASMS Conference was held virtually on August 28-31, 2023, using the Gather.Town platform to bring together scientists in the MS field. The conference offered a 4-day agenda with a scientific program consisting of two plenary lectures, and 14 parallel symposia in which a total of 70 speakers presented technological innovations and their applications in proteomics and biological MS and metabo-lipidomics and pharmaceutical MS. In addition, 16 invited speakers/panelists presented at two research-focused and three career development workshops. Moreover, 86 posters, 12 lightning talks, 3 sponsored workshops, and 11 exhibitions were presented, from which 9 poster awards and 2 lightning talk awards were selected. Furthermore, the conference featured four young investigator awardees to highlight early-career achievements in MS from our society. The conference provided a unique scientific platform for young scientists (i.e. graduate students, postdocs, and junior faculty/investigators) to present their research, meet with prominent scientists, learn about career development, and job opportunities (http://casms.org).
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Espectrometria de Massas , Lipidômica , Preparações Farmacêuticas , Proteômica , Congressos como AssuntoRESUMO
Polyomavirus (PyV) Large T-antigen (LT) is the major viral regulatory protein that targets numerous cellular pathways for cellular transformation and viral replication. LT directly recruits the cellular replication factors involved in initiation of viral DNA replication through mutual interactions between LT, DNA polymerase alpha-primase (Polprim), and single-stranded DNA binding complex, (RPA). Activities and interactions of these complexes are known to be modulated by post-translational modifications; however, high-sensitivity proteomic analyses of the PTMs and proteins associated have been lacking. High-resolution liquid chromatography tandem mass spectrometry (LC-MS/MS) of the immunoprecipitated factors (IPMS) identified 479 novel phosphorylated amino acid residues (PAARs) on the three factors; the function of one has been validated. IPMS revealed 374, 453, and 183 novel proteins associated with the three, respectively. A significant transcription-related process network identified by Gene Ontology (GO) enrichment analysis was unique to LT. Although unidentified by IPMS, the ETS protooncogene 1, transcription factor (ETS1) was significantly overconnected to our dataset indicating its involvement in PyV processes. This result was validated by demonstrating that ETS1 coimmunoprecipitates with LT. Identification of a novel PAAR that regulates PyV replication and LT's association with the protooncogenic Ets1 transcription factor demonstrates the value of these results for studies in PyV biology.
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Replicação do DNA , Polyomavirus , Proteômica , Replicação Viral , Fosforilação , Humanos , Proteômica/métodos , Polyomavirus/metabolismo , Polyomavirus/genética , Espectrometria de Massas em Tandem , Proteína Proto-Oncogênica c-ets-1/metabolismo , Proteína Proto-Oncogênica c-ets-1/genética , Cromatografia Líquida , Antígenos Virais de Tumores/metabolismo , Antígenos Virais de Tumores/genética , Processamento de Proteína Pós-Traducional , DNA Viral/metabolismo , DNA Viral/genéticaRESUMO
Pancreatic cancer patients have poor survival rates and are frequently treated using gemcitabine (Gem). However, initial tumor sensitivity often gives way to rapid development of resistance. Gem-based drug combinations are employed to increase efficacy and mitigate resistance, but our understanding of molecular-level drug interactions, which could assist in the development of more effective therapeutic regimens, is limited. Global quantitative proteomic analysis could provide novel mechanistic insights into drug combination interactions, but it is challenging to achieve high-quality quantitative proteomics analysis of the large sample sets that are typically required for drug combination studies. Here, we investigated molecular-level temporal interactions of Gem with BGJ398 (infigratinib), a recently approved pan-FGFR inhibitor, in multiple treatment groups (N = 42 samples) using IonStar, a robust large-scale proteomics method that employs well-controlled, ultrahigh-resolution MS1 quantification. A total of 5514 proteins in the sample set were quantified without missing data, requiring >2 unique peptides/protein, <1% protein false discovery rate (FDR), <0.1% peptide FDR, and CV < 10%. Functional analysis of the differentially altered proteins revealed drug-dysregulated processes such as metabolism, apoptosis, and antigen presentation pathways. These changes were validated experimentally using Seahorse metabolic assays and immunoassays. Overall, in-depth analysis of large-scale proteomics data provided novel insights into possible mechanisms by which FGFR inhibitors complement and enhance Gem activity in pancreatic cancers.
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Neoplasias Pancreáticas , Proteoma , Humanos , Proteoma/análise , Proteômica/métodos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/metabolismo , Gencitabina , Peptídeos/análise , Apoptose , Quimioterapia Combinada , Combinação de Medicamentos , Linhagem Celular Tumoral , Neoplasias PancreáticasRESUMO
Tumor-stroma interactions are critical in pancreatic ductal adenocarcinoma (PDAC) progression and therapeutics. Patient-derived xenograft (PDX) models recapitulate tumor-stroma interactions, but the conventional antibody-based immunoassay is inadequate to discriminate tumor and stromal proteins. Here, we describe a species-deconvolved proteomics approach embedded in IonStar that can unambiguously quantify the tumor (human-derived) and stromal (mouse-derived) proteins in PDX samples, enabling unbiased investigation of tumor and stromal proteomes with excellent quantitative reproducibility. With this strategy, we studied tumor-stroma interactions in PDAC PDXs that responded differently to Gemcitabine combined with nab-Paclitaxel (GEM+PTX) treatment. By analyzing 48 PDX animals 24 h/192 h after treatment with/without GEM+PTX, we quantified 7262 species-specific proteins under stringent cutoff criteria, with high reproducibility. For the PDX sensitive to GEM+PTX, the drug-dysregulated proteins in tumor cells were involved in suppressed oxidative phosphorylation and the TCA cycle, and in the stroma, inhibition of glycolytic activity was predominant, suggesting a relieved reverse Warburg effect by the treatment. In GEM+PTX-resistant PDXs, protein changes suggested extracellular matrix deposition and activation of tumor cell proliferation. Key findings were validated by immunohistochemistry (IHC). Overall, this approach provides a species-deconvolved proteomic platform that could advance cancer therapeutic studies by enabling unbiased exploration of tumor-stroma interactions in the large number of PDX samples required for such investigations.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Animais , Humanos , Camundongos , Carcinoma Ductal Pancreático/tratamento farmacológico , Linhagem Celular Tumoral , Gencitabina , Xenoenxertos , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Neoplasias Pancreáticas/patologia , Proteômica , Reprodutibilidade dos TestesRESUMO
Accurate, absolute liquid chromatography-mass spectrometry (LC-MS)-based quantification of target proteins in formalin-fixed paraffin-embedded (FFPE) tissues would greatly expand sample availability for pharmaceutical/clinical investigations but remains challenging owing to the following issues: (i) efficient/quantitative recovery of target signature peptides from FFPE tissues is essential but an optimal procedure for targeted, absolute quantification is lacking; (ii) most FFPE samples are long-term-stored; severe immunohistochemistry (IHC) signal losses of target proteins during storage were widely reported, while the effect of storage on LC-MS-based methods was unknown; and (iii) the proper strategy to prepare calibration/quality-control samples to ensure accurate targeted protein analysis in FFPE tissues remained elusive. Using targeted quantification of monoclonal antibody (mAb), antigen, and 40 tissue markers in FFPE tissues as a model system, we extensively investigate those issues and develope an LC-MS-based strategy enabling accurate and precise targeted protein quantification in FFPE samples. First, we demonstrated a surfactant cocktail-based procedure (f-SEPOD), providing high/reproducible recovery of target signature peptides from FFPE tissues. Second, a heat-accelerated degradation study within a roughly estimated 5 year storage period recapitulated the loss of protein IHC signals while LC-MS signals of all targets remained constant. This indicates that the storage of FFPE tissues mainly causes decreased immunoreactivity but unlikely chemical degradation of proteins, which strongly suggests that the storage of FFPE tissues does not cause significant quantitative bias for LC-MS-based methods. Third, while a conventional spike-and-extract approach for calibration caused substantial negative biases, a novel approach, using FFPE-treated calibration standards, enabled accurate and precise quantification. With the pipeline, we conducted the first-ever pharmacokinetics measurement of mAb and its target in FFPE tissues, where time courses by FFPE vs fresh tissues showed excellent correlation.
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Peptídeos , Espectrometria de Massas em Tandem , Cromatografia Líquida/métodos , Inclusão em Parafina , Anticorpos Monoclonais/farmacocinética , Formaldeído/química , Fixação de TecidosRESUMO
Small organic molecules which can emit fluorescence with tunable dual emission bands are significant for fundamental research and broad applications. In this work, two binaphthyl based arylacrylonitrile derivatives with pyrene and triphenylamine unit (BiNp-Py and BiNp-TPA) were designed and synthesized, respectively, featuring chiral backbone and dual AIE-active cyanostyrene-linked chromophores. Excellent fluorescence emissions in a range of solution and solid states were observed with high quantum yields, indicative of the solvatochromism and mechanochromism. More interestingly, dual emission bands were found and tunable by the water fraction in THF, and speculatively attributed to the balancing of intramolecular charge transfer (ICT) and locally excited (LE) emission in solution and aggregate states. Furthermore, the potential application in anti-counterfeiting ink was also explored, indicating the very low concentration (5â ppm) for sufficient distinguishable vision and small colour migration (28â nm) for printing on the filter. The present work provides a new strategy to design organic luminescent structure having widely fluorescent emissions in dual states and a valuable reference for the study of chiral optical materials.
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BACKGROUND AND AIM: Lugol chromoendoscopy is the standard technique to detect an esophageal squamous cell carcinoma (ESCC). However, a high concentration of Lugol's solution can induce mucosal injury and adverse events. We aimed to investigate the optimal concentration of Lugol's solution to reduce mucosal injury and adverse events without degrading image quality. METHODS: This was a two-phase double-blind randomized controlled trial. In phase I, 200 eligible patients underwent esophagogastroduodenoscopy and then were randomly (1:1:1:1:1) sprayed with 1.2%, 1.0%, 0.8%, 0.6%, or 0.4% Lugol's solution. Image quality, gastric mucosal injury, adverse events, and operation satisfaction were compared to investigate the minimal effective concentration. In phase II, 42 cases of endoscopic mucosectomy for early ESCC were included. The patients were randomly assigned (1:1) to the minimal effective (0.6%) or conventional (1.2%) concentration of Lugol's solution for further comparison of the effectiveness. RESULTS: In phase I, the gastric mucosal injury was significantly reduced in 0.6% group (P < 0.05). Furthermore, there was no statistical significance in image quality between 0.6% and higher concentrations of Lugol's solution (P > 0.05, respectively). It also showed that the operation satisfaction decreased in 1.2% group compared with the lower concentration groups (P < 0.05). In phase II, the complete resection rate was 100% in both groups, while 0.6% Lugol's solution showed higher operation satisfaction (W = 554.500, P = 0.005). CONCLUSIONS: The study indicates that 0.6% might be the optimal concentration of Lugol's solution for early detection and delineation of ESCC, considering minimal mucosal injury and satisfied image. The registry of clinical trials: ClinicalTrials.gov (NCT03180944).
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Neoplasias Esofágicas/patologia , Esofagoscopia/métodos , CorantesRESUMO
Optical fiber sensors are used for partial discharge detection in many applications due their advantage of strong anti-electromagnetic interference capability. Multi-point distributed partial discharge detection and location are important for electrical equipment. In this paper, a distributed partial discharge location and detection scheme based on optical fiber Rayleigh backscattering light interference is experimentally demonstrated. At the same time, the location and extraction algorithm is used to demodulate the partial discharge signal; furthermore, the high-pass filter is used to reduce the system low-frequency noise and environment noise. It is clear that the proposed system can detect a partial discharge signal generated by metal needle sensitivity, and the detectable frequency range is 0-2.5 kHz. We carried out 10 locating tests for two sensing units, the experimental results show that the maximum location error is 1.0 m, and the maximum standard deviation is 0.3795. At same time, the signal-to-noise ratio (SNR) of sensing unit 1 and sensing unit 2 are greatly improved after demodulation, which are 39.7 and 38.8, respectively. This provides a new method for a multipoint-distributed optical fiber sensor used for detecting and locating a long-distance electrical equipment partial discharge signal.
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Proteomics analysis of circulating exosomes derived from cancer cells represents a promising approach to the elucidation of cell-cell communication and the discovery of putative biomarker candidates for cancer diagnosis and treatment. Nonetheless, the proteome of exosomes derived from cell lines with different metastatic capabilities still warrants further investigation. Here, we present a comprehensive quantitative proteomics investigation of exosomes isolated from immortalized mammary epithelial cells and matched tumor lines with different metastatic potentials in an attempt to discover exosome markers specific to breast cancer (BC) metastasis. A total of 2135 unique proteins were quantified with a high confidence level from 20 isolated exosome samples, including 94 of the TOP 100 exosome markers archived by ExoCarta. Moreover, 348 altered proteins were observed, among which several metastasis-specific markers, including cathepsin W (CATW), magnesium transporter MRS2 (MRS2), syntenin-2 (SDCB2), reticulon-4 (RTN), and UV excision repair protein RAD23 homolog (RAD23B), were also identified. Notably, the abundance of these metastasis-specific markers corresponds well with the overall survival of BC patients in clinical settings. Together, these data provide a valuable dataset for BC exosome proteomics investigation and prominently facilitate the elucidation of the molecular mechanisms underlying primary tumor development and progression.
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Biomarcadores Tumorais , Neoplasias da Mama , Exossomos , Feminino , Humanos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Exossomos/metabolismo , Proteômica , Metástase Neoplásica , Biomarcadores Tumorais/metabolismoRESUMO
Age-related macular degeneration (AMD) is the leading cause of blindness in elderly people, with limited treatment options available for most patients. AMD involves the death of retinal pigment epithelium (RPE) and photoreceptor cells, with mitochondria dysfunction being a critical early event. In the current study, we utilized our unique resource of human donor RPE graded for AMD presence and severity to investigate proteome-wide dysregulation involved in early AMD. Organelle-enriched fractions of RPE were isolated from donors with early AMD (n = 45) and healthy age-matched controls (n = 32) and were analyzed by UHR-IonStar, an integrated proteomics platform enabling reliable and in-depth proteomic quantification in large cohorts. A total of 5941 proteins were quantified with excellent analytical reproducibility, and with further informatics analysis, many biological functions and pathways were found to be significantly dysregulated in donor RPE samples with early AMD. Several of these directly pinpointed changes in mitochondrial functions, e.g., translation, ATP metabolic process, lipid homeostasis, and oxidative stress. These novel findings highlighted the value of our proteomics investigation by allowing a better understanding of the molecular mechanisms underlying early AMD onset and facilitating both treatment development and biomarker discovery.