Simultaneous occurrence of papillary thyroid carcinoma, medullary thyroid carcinoma, and lymphoma: A case report.

BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer, the coexistence of PTC and medullary thyroid carcinoma (MTC) is uncommon. While the simultaneous occurrence of both cancers with small lymphocytic lymphoma (SLL) in lymph nodes with PTC metastasis is very rare. This study presents a unique case of concurrent PTC, MTC, and SLL, highlighting the exceptional rarity of these coexisting tumors. METHODS: A 75-year-old female with a thyroid tumor underwent total thyroidectomy, bilateral central neck lymph node dissection, and right radical neck lymph node dissection. Histopathological examination revealed a low-grade medullary thyroid carcinoma (MTC) in the left lobe and classical papillary thyroid carcinoma (PTC) in the right lobe, with PTC metastasis in the cervical lymph nodes and concurrent SLL in the affected lymph nodes. RESULTS: Coexistence of PTC, MTC and SLL in the same patient is rare, there are currently no standardized treatment guidelines due to the limited literature. However, it is essential to consider not only the treatment for each type of tumor but also the potential risks or conflicts associated with the treatments. In the case reported in this paper, the papillary carcinoma invaded the capsule of the right lobe of the thyroid and metastasized to the cervical lymph nodes, warranting radioactive iodine therapy. However, considering the potential negative impact of radioactive iodine on the pre-existing lymphoma, the radioactive iodine therapy was postponed. Meanwhile, constant monitoring of calcitonin and thyroid globulin should be performed to monitor tumor recurrence as was performed in the present case. CONCLUSION: Since MTC, PTC, and SLL may coexist, patients with PTC deserve careful surveillance for the other disease entities. This case underscores the need for heightened awareness among clinicians, radiologists, and pathologists regarding the possibility of concurrent thyroid tumors and abnormal lymph nodes, guiding comprehensive pre-operative evaluations and postoperative monitoring strategies. This study aims to provide a warning for routine pathological diagnosis and contribute data for related research.

Ochratoxin A-induced DNA damage triggers G2 phase arrest via hMLH1-p53-p21 signaling pathway in human gastric epithelium immortalized cells in vitro.

Ochratoxin A (OTA), as one of the most important and harmful mycotoxins, is classed as possible human carcinogen (group 2B). As we all know, DNA damage may cause genomic instability, cell cycle disorder, activation of DNA damage pathway, and stimulation of DNA repair system. To explore the roles of DNA damage repair protein (hMLH1) on OTA-induced G2 arrest, the DNA damage, chromosome aberration, cell cycle distribution and p53-p21 signaling pathway were evaluatd after different time OTA exposure (6, 12, 24, 48h) in immortalized human gastric epithelial cells (GES-1). Our results demonstrated that OTA exposure could trigger genomic instability, DNA damage and G2 phase arrest of GES-1 cells. At the same time, OTA treatment could increase the expression of hMLH1, and induce phosphorylation of the p53 protein, as well as p21, in response to DNA damage. Finally, inhibition of hMLH1 by siRNA effectively prevented the activation of p53-p21 signaling pathway and rescued the G2 arrest elicited by OTA. This study demonstrated that hMLH1-p53-p21 signaling pathway played an important role in DNA damage and G2 cell cycle arrest the mediated by OTA in GES-1 cells.

Nanopore Direct RNA Sequencing Reveals Virus-Induced Changes in the Transcriptional Landscape in Human Bronchial Epithelial Cells.

Direct RNA nanopore sequencing reveals changes in gene expression, polyadenylation, splicing, m6A methylation, and pseudouridylation in response to influenza virus exposure in primary human bronchial epithelial cells. This study focuses on the epitranscriptomic profile of genes in the host immune response. In addition to polyadenylated noncoding RNA, we purified and sequenced nonpolyadenylated noncoding RNA and observed changes in expression, N6-methyl-adenosine (m6A), and pseudouridylation (Ψ) in these novel RNA. Two recently discovered lincRNA with roles in immune response, Chaserr and LEADR , became highly methylated in response to influenza exposure. Several H/ACA type snoRNAs that guide pseudouridylation are decreased in expression in response to influenza, and there is a corresponding decrease in the pseudouridylation of two novel lncRNA. Thus, novel epitranscriptomic changes revealed by direct RNA sequencing with nanopore technology provides unique insights into the host epitranscriptomic changes in epithelial gene networks that respond to influenza virus infection.

Influenza virus infection exacerbates gene expression related to neurocognitive dysfunction in brains of old mice.

BACKGROUND: Age > 65 years is a key risk factor for poor outcomes after human influenza infection. Specifically, in addition to respiratory disease, non-neurotropic influenza A virus (IAV) causes neuro-cognitive complications, e.g. new onset depression and increases the risk of dementia after hospitalization. This study aimed to identify potential mechanisms of these effects by determining differences between young and old mice in brain gene expression in a mouse model of non-neurotropic IAV infection. METHODS: Young (12 weeks) and old (70 weeks) C57Bl/6J mice were inoculated intranasally with 200 PFU H1N1 A/PR/34/8 (PR8) or sterile PBS (mock). Gene expression in lung and brain was measured by qRT-PCR and normalized to ß-actin. Findings were confirmed using the nCounter Mouse Neuroinflammation Array (NanoString) and analyzed with nSolver 4.0 and Ingenuity Pathway Analysis (IPA, Qiagen). RESULTS: IAV PR8 did not invade the central nervous system. Young and old mice differed significantly in brain gene expression at baseline and during non-neurotropic IAV infection. Expression of brain Ifnl, Irf7, and Tnf mRNAs was upregulated over baseline control at 3 days post-infection (p.i.) only in young mice, but old mice expressed more Ifnl than young mice 7 days p.i. Gene arrays showed down-regulation of the Epigenetic Regulation, Insulin Signaling, and Neurons and Neurotransmission pathways in old mice 3 days p.i. while young mice demonstrated no change or induction of these pathways at the same time point. IPA revealed marked baseline differences between old and young mice. Gene expression related to Cognitive Impairment, Memory Deficits and Learning worsened in old mice relative to young mice during IAV infection. Aged mice demonstrate more severe changes in gene expression related to memory loss and cognitive dysfunction by IPA. CONCLUSIONS: These data suggest the genes and pathways related to learning and cognitive performance that were worse at baseline in old mice were further worsened by IAV infection, similar to old patients. Early events in the brain triggered by IAV infection portend downstream neurocognitive pathology in old adults.

Neuropeptidomics of the American Lobster Homarus americanus.

The American lobster, Homarus americanus, is not only of considerable economic importance but has also emerged as a premier model organism in neuroscience research. Neuropeptides, an important class of cell-to-cell signaling molecules, play crucial roles in a wide array of physiological and psychological processes. Leveraging the recently sequenced high-quality draft genome of the American lobster, our study sought to profile the neuropeptidome of this model organism. Employing advanced mass spectrometry techniques, we identified 24 neuropeptide precursors and 101 unique mature neuropeptides in Homarus americanus. Intriguingly, 67 of these neuropeptides were discovered for the first time. Our findings provide a comprehensive overview of the peptidomic attributes of the lobster's nervous system and highlight the tissue-specific distribution of these neuropeptides. Collectively, this research not only enriches our understanding of the neuronal complexities of the American lobster but also lays a foundation for future investigations into the functional roles that these peptides play in crustacean species. The mass spectrometry data have been deposited in the PRIDE repository with the identifier PXD047230.

An Updated Guide to the Identification, Quantitation, and Imaging of the Crustacean Neuropeptidome.

Crustaceans serve as a useful, simplified model for studying peptides and neuromodulation, as they contain numerous neuropeptide homologs to mammals and enable electrophysiological studies at the single-cell and neural circuit levels. Crustaceans contain well-defined neural networks, including the stomatogastric ganglion, oesophageal ganglion, commissural ganglia, and several neuropeptide-rich organs such as the brain, pericardial organs, and sinus glands. As existing mass spectrometry (MS) methods are not readily amenable to neuropeptide studies, there is a great need for optimized sample preparation, data acquisition, and data analysis methods. Herein, we present a general workflow and detailed methods for MS-based neuropeptidomic analysis of crustacean tissue samples and circulating fluids. In conjunction with profiling, quantitation can also be performed with isotopic or isobaric labeling. Information regarding the localization patterns and changes of peptides can be studied via mass spectrometry imaging. Combining these sample preparation strategies and MS analytical techniques allows for a multi-faceted approach to obtaining deep knowledge of crustacean peptidergic signaling pathways.

EndoGenius: Optimized Neuropeptide Identification from Mass Spectrometry Datasets.

Neuropeptides represent a unique class of signaling molecules that have garnered much attention but require special consideration when identifications are gleaned from mass spectra. With highly variable sequence lengths, neuropeptides must be analyzed in their endogenous state. Further, neuropeptides share great homology within families, differing by as little as a single amino acid residue, complicating even routine analyses and necessitating optimized computational strategies for confident and accurate identifications. We present EndoGenius, a database searching strategy designed specifically for elucidating neuropeptide identifications from mass spectra by leveraging optimized peptide-spectrum matching approaches, an expansive motif database, and a novel scoring algorithm to achieve broader representation of the neuropeptidome and minimize reidentification. This work describes an algorithm capable of reporting more neuropeptide identifications at 1% false-discovery rate than alternative software in five Callinectes sapidus neuronal tissue types.

Quantifying the contribution of methane diffusion and ebullition from agricultural ditches.

Agricultural ditches are significant methane (CH4) sources since substantial nutrient inputs stimulate CH4 production and emission. However, few studies have quantified the role of diffusion and ebullition pathways in total CH4 emission from agricultural ditches. This study measured the spatiotemporal variations of diffusive and ebullitive CH4 fluxes from a multi-level ditch system in a typical temperate agriculture area, and assessed their contributions to the total CH4 emission. Results illustrated that the mean annual CH4 flux in the ditch system reached 1475.1 mg m-2 d-1, among which 1376.7 mg m-2 d-1 was emitted via diffusion and 98.5 mg m-2 d-1 via ebullition. Both diffusive and ebullitive fluxes varied significantly across different types of ditches and seasons, with diffusion dominating CH4 emission in middle-size ditches and ebullition dominating in large-size ditches. Diffusion was primarily driven by large nutrient inputs from adjacent farmlands, while hydrological factors like water temperature and depth controlled ebullition. Overall, CH4 emission accounted for 86 % of the global warming potential across the ditch system, with 81 % attributed to diffusion and 5 % to ebullition. This study highlights the importance of agricultural ditches as hotspots for CH4 emissions, particularly the dominant role of the diffusion pathway.

On-Tissue Spatial Proteomics Integrating MALDI-MS Imaging with Shotgun Proteomics Reveals Soy Consumption-Induced Protein Changes in a Fragile X Syndrome Mouse Model.

Fragile X syndrome (FXS), the leading cause of inherited intellectual disability and autism, is caused by the transcriptional silencing of the FMR1 gene, which encodes the fragile X messenger ribonucleoprotein (FMRP). FMRP interacts with numerous brain mRNAs that are involved in synaptic plasticity and implicated in autism spectrum disorders. Our published studies indicate that single-source, soy-based diets are associated with increased seizures and autism. Thus, there is an acute need for an unbiased protein marker identification in FXS in response to soy consumption. Herein, we present a spatial proteomics approach integrating mass spectrometry imaging with label-free proteomics in the FXS mouse model to map the spatial distribution and quantify levels of proteins in the hippocampus and hypothalamus brain regions. In total, 1250 unique peptides were spatially resolved, demonstrating the diverse array of peptidomes present in the tissue slices and the broad coverage of the strategy. A group of proteins that are known to be involved in glycolysis, synaptic transmission, and coexpression network analysis suggest a significant association between soy proteins and metabolic and synaptic processes in the Fmr1KO brain. Ultimately, this spatial proteomics work represents a crucial step toward identifying potential candidate protein markers and novel therapeutic targets for FXS.

Incidence and risk factors of lymph node metastasis in breast cancer patients without preoperative chemoradiotherapy and neoadjuvant therapy: analysis of SEER data.

Background: Breast cancer (BC) is the leading cause of death in the female reproductive system, often linked to lymph node involvement, indicating poor prognosis. This study investigated lymph node metastasis incidence and risk factors in M0 stage BC patients who hadn't received preoperative chemoradiotherapy or neoadjuvant therapy. We explored the influence of various factors on lymph node metastasis. Methods: We conducted a retrospective analysis using Surveillance, Epidemiology, and End Results data from BC patients diagnosed between 2010 and 2015. Binary logistic regression and propensity score matching (PSM) assessed significant factors in BC patients without preoperative treatment. We developed predictive nomograms and evaluated model performance using the concordance index, calibration curve, area under the curve, and decision curve analysis. Results: Among 256,504 eligible BC patients, 25.57% had lymph node metastasis. Multivariate logistic regression revealed associations between lymph node metastasis and younger age, African-American ethnicity, central/nipple location, lobular carcinoma, human epidermal growth factor receptor 2 (HER2)-positive status, grade III classification, and T3 stage. PSM confirmed these findings. Interactions were identified between age, race, primary site, histology, breast subtype, grade, and T stage, all influencing lymph node metastasis. Conclusions: This retrospective study identified lymph node metastasis in female BC patients with distinct clinicopathological characteristics who received no preoperative treatment. We constructed valuable nomograms, revealing that: (I) young age (<35 years), African-American race, central/nipple location, infiltrating duct carcinoma, HER2 positivity, high histological grade (grade III), and larger tumor size are risk factors for regional lymph node metastasis; (II) lymph node metastasis may not solely represent the invasive nature of triple-negative BC; (III) patients with different BC subtypes in T1c-T2 stages may benefit from individualized neoadjuvant treatment strategies.

Enhanced Degradation of Levofloxacin through Visible-Light-Driven Peroxymonosulfate Activation over CuInS2/g-C3N4 Heterojunctions.

In this work, the heterojunctions of CuInS2 embedded in the g-C3N4 materials (xCuInS2/g-C3N4, abbreviated as xCIS/GCN) was successfully prepared for peroxymonosulfate (PMS) activation under visible light. The catalysts are characterized by different techniques, such as XRD, FTIR, SEM, TEM, and UV-vis. The unique heterojunction composites can suppress the recombination of photogenerated pairs. The catalytic results showed that the 3CIS/GCN exhibited excellent catalytic levofloxacin (LVF) degradation efficiency, while more than 98.9% of LVF was removed in 60 min over a wide pH range. SO4•-, O2•-, OH•, and 1O2 were verified as the main reactive species for LVF degradation via the quenching experiments and electron paramagnetic resonance technology (EPR). The synergetic effect of xCIS/GCN, PMS, and visible light irradiation was discussed. The possible LVF degradation pathway was proposed through byproducts analysis (LC-MS). Moreover, the 3CIS/GCN/vis-PMS system has very low metal leaching. Owing to xCIS/GCN having good properties for PMS activation, it has potential applications for LVF or other hazardous pollutants degradation.