A case report of breast cancer metastasis to the bladder from invasive ductal carcinoma.

Introduction and importance: Breast cancer is the most common malignancy among women worldwide, predominantly manifesting as invasive ductal carcinoma (IDC), which usually metastasizes to the bones, lungs, and liver. However, metastasis to the bladder is exceedingly rare, with few documented cases and limited understanding in the existing literature. Case presentation: A 57-year-old woman with a history of IDC presented with a lump in her left breast and was initially treated with chemotherapy and a modified radical mastectomy. Years later, she developed urinary symptoms, which upon investigation revealed multiple bladder tumors and right kidney hydronephrosis. Diagnostic imaging, including ultrasound and computed tomography (CT) scans, supported these findings. Clinical discussion: The discovery of bladder metastasis from IDC highlights significant diagnostic challenges due to the atypical presentation. The case underscores the importance of considering unusual metastatic sites in patients with known breast cancer, especially when they present with non-specific urinary symptoms. This report explores the potential pathophysiological mechanisms of such rare metastatic occurrences and discusses the implications for clinical practice. Conclusion: This case exemplifies the critical need for heightened awareness and thorough evaluation in patients with unusual symptoms and a history of breast cancer. It calls for more comprehensive diagnostic approaches and possibly adjusted treatment protocols to better manage atypical metastases, ultimately aiming to improve patient outcomes and contribute to a deeper understanding of metastatic breast cancer behavior.

Impact of coronary collateralization on major adverse cardiovascular and cerebrovascular events after successful recanalization of chronic total occlusion.

Aims: This study aims to investigate the effects of coronary collateral circulation (CCC) on the prognosis of chronic total occlusion (CTO) patients with or without metabolic syndrome (MetS). Methods: The study included 342 CTO patients who underwent successful percutaneous coronary intervention at the People's Hospital of Liaoning Province between 1 February 2021 and 30 September 2023. The Rentrop score was used to assess the status of CCC. The outcome was major adverse cardiovascular and cerebrovascular events (MACCEs), defined as a composite of all-cause mortality, cardiac death, non-fatal myocardial infarction (MI), target vessel revascularization (TVR), and non-fatal stroke. Univariate and multivariate logistic analyses were used to investigate the association of CCC, MetS, and MACCEs with odds ratios (ORs) and 95% confidence intervals (CIs). The effect of CCC was further investigated in different MetS, diabetes mellitus (DM), and Syntax score groups. Results: MACCEs were more common in patients with poor CCC compared to those with good CCC (38.74% vs. 16.56%). Statistical differences were found in MACCEs (OR = 3.33, 95% CI: 1.93-5.72), MI (OR = 3.11, 95% CI: 1.73-5.58), TVR (OR = 3.06, 95% CI: 1.70-5.53), and stent thrombosis (OR = 6.14, 95% CI: 2.76-13.65) between the good and poor CCC groups. Poor CCC patients with MetS had a higher incidence of MACCEs (OR = 4.21, 95% CI: 2.05-8.65), non-fatal MI (OR = 4.44, 95% CI: 2.01-9.83), TVR (OR = 3.28, 95% CI: 1.51-7.11), and stent thrombosis (OR = 10.80, 95% CI: 3.11-37.54). Similar findings were also observed in CTO patients with DM and a Syntax score ≥23. Conclusion: Poor CCC could increase the risk of MACCEs in CTO patients, particularly those with MetS, DM, and a Syntax score ≥23. Further prospective, multicenter studies are needed to validate our findings and to explore potential therapeutic interventions.

Identification of Synonymous Pathogenic Variants in Monogenic Disorders by Integrating Exome with Transcriptome Sequencing.

Exome sequencing is becoming a first-tier clinical diagnostic test for Mendelian diseases, drastically reducing the time and cost of diagnostic odyssey and improving the diagnosis rate. Despite its success, exome sequencing faces practical challenges in assessing the pathogenicity of numerous intronic and synonymous variants, leaving a significant proportion of patients undiagnosed. In this study, a whole-blood transcriptome database was constructed that showed the expression profile of 2981 Online Mendelian Inheritance in Man disease genes in blood samples. Meanwhile, a workflow integrating exome sequencing, blood transcriptome sequencing, and in silico prediction tools to identify and validate splicing-altering intronic or synonymous variants was proposed. Following this pipeline, seven synonymous variants in eight patients were discovered. Of these, the functional evidence of c.981G>A (PIGN), c.1161A>G (ALPL), c.858G>A (ATP6AP2), and c.1011G>T (MTHFR) have not been reported previously. RNA sequencing validation confirmed that these variants induced aberrant splicing, expanding the disease-causing variant spectrum of these genes. Overall, this study shows the feasibility of combining multi-omics data to identify splicing-altering variants, especially the power of RNA sequencing. It also reveals that synonymous variants, which often are overlooked in standard diagnostic approaches, comprise an important portion of unresolved genetic diseases.

N-doped graphene aerogel cathode with internal aeration for enhanced degradation of p-nitrophenol by electro-Fenton process.

A columnar N-doped graphene aerogel (NGA) was successfully fabricated by one-step hydrothermal synthesis using L-hydroxyproline as reductant, N-doping, and swelling agent, and it was used as the cathode with internal aeration mode for the electro-Fenton degradation of p-nitrophenol. Owing to the stable solid-liquid-gas three-phase interface, more active defects, and modulated nitrogen dopants, the NGA cathode exhibited enhanced electrocatalytic activity. H2O2 could be continuously electro-generated via a two-electron oxygen reduction, and the yield of H2O2 was 153.3 mg·L-1·h-1 with the low electric energy consumption of 15.3 kWh kg-1. Simultaneously, the NGA cathode had better charge transfer capability with N-doping, which was conducive to the conversion of Fe3+/Fe2+. Under the optimal condition, nearly 100% removal of p-nitrophenol and 84% removal of TOC were obtained within 60 and 120 min, respectively. The NGA cathode also presented good stability and versatile applicability in different water matrices. Therefore, the NGA is a cost-effective cathode material in electro-Fenton system with adequate activity and reuse stabilization.

Global burden of thyroid cancer and its attributable risk factors in 204 countries and territories from 1990 to 2019.

BACKGROUND: To investigate the burden of thyroid cancer and its attributable risk factors in 204 countries and territories during 30 years. METHODS: We extracted data from the Global Burden of Disease (GBD) 2019 database, including incidence, mortality, disability-adjusted life-years (DALYs), and the attributable risk factors of thyroid cancer from 1990 to 2019. Estimated annual percentage changes (EAPC) were calculated to assess the changes in age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), and age-standardized DALYs rate (ASDR). We also examined the associations between cancer burden and the sociodemographic index (SDI). RESULTS: The global new cases, death, and DALYs of thyroid cancer in 2019 were 233 847 (95% UI: 211 637-252 807), 45 576 (95% UI: 41 290-48 775), and 1 231 841 (95% UI: 1 113 585-1 327 064), respectively. From 1990 to 2019, the ASIR of thyroid cancer showed an upward trend (EAPC = 1.25), but ASMR (EAPC = -0.15) and ASDR (EAPC = -0.14) decreased. The burden of thyroid cancer varied at regional and national levels, but the association between ASIR and SDI was positive. We found that the burden of thyroid cancer was mainly concentrated in females and that the age of onset tended to be younger. The proportion of DALYs from thyroid cancer attributable to high body-mass index was higher in high SDI regions, especially in males. CONCLUSIONS: The global incidence of thyroid cancer has continued to increase in the past three decades. The high body-mass index as an important risk factor for thyroid cancer deserves greater attention, especially in high SDI regions.

Identification and evaluation of reference genes for quantitative real-time PCR analysis in Polygonum cuspidatum based on transcriptome data.

BACKGROUND: Polygonum cuspidatum of the Polygonaceae family is a traditional medicinal plant with many bioactive compounds that play important roles in human health and stress responses. Research has attempted to identify biosynthesis genes and metabolic pathways in this species, and quantitative real-time PCR (RT-qPCR) has commonly been used to detect gene expression because of its speed, sensitivity, and specificity. However, no P. cuspidatum reference genes have been identified, which hinders gene expression studies. Here, we aimed to identify suitable reference genes for accurate and reliable normalization of P. cuspidatum RT-qPCR data. RESULTS: Twelve candidate reference genes, including nine common (ACT, TUA, TUB, GAPDH, EF-1γ, UBQ, UBC, 60SrRNA, and eIF6A) and three novel (SKD1, YLS8, and NDUFA13), were analyzed in different tissues (root, stem, and leaf) without treatment and in leaves under abiotic stresses (salt, ultraviolet [UV], cold, heat, and drought) and hormone stimuli (abscisic acid [ABA], ethylene [ETH], gibberellin [GA3], methyl jasmonate [MeJA], and salicylic acid [SA]). Expression stability in 65 samples was calculated using the △CT method, geNorm, NormFinder, BestKeeper, and RefFinder. Two reference genes (NDUFA13 and EF-1γ) were sufficient to normalize gene expression across all sample sets. They were also the two most stable genes for abiotic stresses and different tissues, whereas NDUFA13 and SKD1 were the top two choices for hormone stimuli. Considering individual experimental sets, GAPDH was the top-ranked gene under ABA, ETH, and GA3 treatments, while 60SrRNA showed good stability under MeJA and cold treatments. ACT, UBC, and TUB were suitable genes for drought, UV, and ABA treatments, respectively. TUA was not suitable because of its considerable variation in expression under different conditions. The expression patterns of PcPAL, PcSTS, and PcMYB4 under UV and SA treatments and in different tissues normalized by stable and unstable reference genes demonstrated the suitability of the optimal reference genes. CONCLUSIONS: We propose NDUFA13 and EF-1γ as reference genes to normalize P. cuspidatum expression data. To our knowledge, this is the first systematic study of reference genes in P. cuspidatum which could help advance molecular biology research in P. cuspidatum and allied species.

Nucleotide-binding oligomerization domain-like receptor X1 restricts porcine reproductive and respiratory syndrome virus-2 replication by interacting with viral Nsp9.

Porcine reproductive and respiratory syndrome virus (PRRSV) causes one of the most economically important diseases of swine worldwide. Current antiviral strategies provide only limited protection. Nucleotide-binding oligomerization domain-like receptor (NLR) X1 is unique among NLR proteins in its functions as a pro-viral or antiviral factor to different viral infections. To date, the impact of NLRX1 on PRRSV infection remains unclear. In this study, we found that PRRSV infection promoted the expression of NLRX1 gene. In turn, ectopic expression of NLRX1 inhibited PRRSV replication in Marc-145 cells, whereas knockdown of NLRX1 enhanced PRRSV propagation in porcine alveolar macrophages (PAMs). Mechanistically, NLRX1 was revealed to impair intracellular viral subgenomic RNAs accumulation. Finally, Mutagenic analyses indicated that the LRR (leucine-rich repeats) domain of NLRX1 interacted with PRRSV Nonstructural Protein 9 (Nsp9) RdRp (RNA-dependent RNA Polymerase) domain and was necessary for antiviral activity. Thus, our study establishes the role of NLRX1 as a new host restriction factor in PRRSV infection.

A WRKY transcription factor, PcWRKY33, from Polygonum cuspidatum reduces salt tolerance in transgenic Arabidopsis thaliana.

KEY MESSAGE: PcWRKY33 is a transcription factor which can reduce salt tolerance by decreasing the expression of stress-related genes and increasing the cellular levels of reactive oxygen species (ROS). WRKY transcription factors play important roles in the regulation of biotic and abiotic stresses. Here, we report a group I WRKY gene from Polygonum cuspidatum, PcWRKY33, that encodes a nucleoprotein, which specifically binds to the W-box in the promoter of target genes to regulate their expression. The results from qPCR and promoter analysis show that expression of PcWRKY33 can be induced by various abiotic stresses, including NaCl and plant hormones. Overexpression of PcWRKY33 in Arabidopsis thaliana reduced tolerance to salt stress. More specifically, several physiological parameters (such as root length, seed germination rate, seedling survival rate, and chlorophyll concentration) of the transgenic lines were significantly lower than those of the wild type under salt stress. In addition, following exposure to salt stress, transgenic plants showed decreased expression of stress-related genes, a weakened ability to maintain Na+/K+ homeostasis, decreased activities of reactive oxygen species- (ROS-) scavenging enzymes, and increased accumulation of ROS. Taken together, these results suggest that PcWRKY33 negatively regulates the salt tolerance in at least two ways: by down-regulating the induction of stress-related genes and by increasing the level of cellular ROS. In sum, our results indicate that PcWRKY33 is a group I WRKY transcription factor involved in abiotic stress regulation.