RESUMEN

Despite improvements in the early intervention of myocardial infarction (MI) in recent decades, left ventricular aneurysms (LVA) remain a major health concern, particularly in developing nations. The progression of MI can lead to the thinning of the myocardial wall and the formation of a ventricular wall bulge, characteristic of an LVA. Furthermore, cardiac magnetic resonance (CMR) has emerged as the gold standard for LVA diagnosis due to its superior imaging capabilities. Notably, surgical ventricular reconstruction (SVR) is an effective treatment for LVA, aiming to restore the normal volume and structure of the left ventricle, thereby improving cardiac function. However, the criteria for selecting patients for SVR treatment remains a subject of debate. This review focuses on the current understanding of surgical indications, procedures, and prognostic risk factors that influence outcomes in left ventricular reconstruction, highlighting the need for precise patient selection to optimize surgical benefits.

RESUMEN

In this study, bacterial cellulose (BC) and BC/locust bean gum (LBG) composite produced from banana hydrolysate were both used as the adsorbent for various organic dyes adsorption especially for malachite green (MG) adsorption for the first time. The BC/LBG(2%) composite exhibited significantly enhanced swelling rate and textural characteristics while maintained the basic structure of BC as depicted by XRD, FT-IR, and NMR, providing a foundation for its application as an excellent adsorbent. The composite exhibited a high adsorption rate and adsorption capacity for MG (exceeding 95 % and 2000 mg/g), and had a good selectivity for MG adsorption in the solution containing crystal violet (CV), rhodamine B (RB), and methyl orange (MO). The MG adsorption process conformed to multiple models including Langmuir and pseudo-first-order models. And the adsorption mechanism mainly comprised chemical adsorption (hydrogen bonding and electrostatic interactions) and physical adsorption. The reusability of BC/LBG(2%) composite was attractive for industrial application that the MG adsorption rate reduced merely a little (still higher than 88 %) after the 5th regeneration process. Overall, considering its adsorption capacity, selectivity, and reusability, BC/LBG(2%) composite prepared by in-situ fermentation with LBG addition was a competent adsorbent for MG adsorption and MG containing wastewater treatment.

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Integrating genomics and histology for cancer prognosis demonstrates promise. Here, we develop a multi-classifier system integrating a lncRNA-based classifier, a deep learning whole-slide-image-based classifier, and a clinicopathological classifier to accurately predict post-surgery localized (stage I-III) papillary renal cell carcinoma (pRCC) recurrence. The multi-classifier system demonstrates significantly higher predictive accuracy for recurrence-free survival (RFS) compared to the three single classifiers alone in the training set and in both validation sets (C-index 0.831-0.858 vs. 0.642-0.777, p < 0.05). The RFS in our multi-classifier-defined high-risk stage I/II and grade 1/2 groups is significantly worse than in the low-risk stage III and grade 3/4 groups (p < 0.05). Our multi-classifier system is a practical and reliable predictor for recurrence of localized pRCC after surgery that can be used with the current staging system to more accurately predict disease course and inform strategies for individualized adjuvant therapy.

Asunto(s)

Carcinoma de Células Renales , Neoplasias Renales , Recurrencia Local de Neoplasia , Humanos , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Neoplasias Renales/genética , Neoplasias Renales/patología , Neoplasias Renales/cirugía , Masculino , Femenino , Recurrencia Local de Neoplasia/genética , Persona de Mediana Edad , Anciano , Pronóstico , Genómica/métodos , Adulto , Estadificación de Neoplasias , Aprendizaje Profundo , Supervivencia sin Enfermedad

RESUMEN

BACKGROUND: Lymphatic metastasis is the major challenge in the treatment of penile cancer. The prognosis of individuals with lymphatic metastasis is extremely poor. Therefore, early identification of disease progression and lymphatic metastasis is an urgent task for researchers in penile cancer worldwide. METHODS: In this study, using single-cell RNA sequencing, an immune landscape was established for the cancer ecosystem based on 46,861 cells from six patients with penile cancer (four with lymphatic metastasis [stage IV] and two without lymphatic metastasis [stage I]). Using bulk RNA sequencing, the discrepancy between the cancers and their respective metastatic lymph nodes was depicted based on seven patients with penile cancer. RESULTS: The interaction between epithelial cells, fibroblasts, and endothelial cells, and the functional cooperation among invasion, epithelial-mesenchymal transition, and angiogenesis were found to be important landscapes in the penile cancer ecosystem, playing important roles in progression of cancer and lymph node metastasis. CONCLUSIONS: This study is the first to investigate the altered tumor microenvironment heterogeneity of penile cancer as it evolves from non-lymphatic to lymphatic metastasis and provides insights into the mechanisms underlying malignant progression, the premetastatic niche, and lymphatic metastasis in penile cancer.

Asunto(s)

Progresión de la Enfermedad , Metástasis Linfática , Neoplasias del Pene , Microambiente Tumoral , Humanos , Masculino , Neoplasias del Pene/patología , Transición Epitelial-Mesenquimal , Análisis de la Célula Individual , Persona de Mediana Edad , Pronóstico , Ganglios Linfáticos/patología

RESUMEN

BACKGROUND: Existing studies have found that circular RNAs (circRNAs) act as sponges for micro RNAs (miRNAs) to control downstream genes. However, the specific functionalities and mechanisms of circRNAs in human clear cell renal cell carcinoma (ccRCC) have yet to be thoroughly investigated. METHODS: Patient cohorts from online databases were used to screen candidate circRNAs, while another cohort from our hospital was obtained for validation. CircSOD2 was identified as a potential oncogenic target, and its relevant characteristics were investigated during ccRCC progression through various assays. A positive feedback loop containing downstream miRNA and its target gene were identified using bioinformatics and validated by luciferase reporter assays, RNA pull-down, and high-throughput sequencing. RESULTS: CircSOD2 expression was elevated in tumor samples and significantly correlated with overall survival (OS) and the tumor stage of ccRCC patients, which appeared in the enhanced proliferation, invasion, and migration of tumor cells. Through competitive binding to circSOD2, miR-532-3p can promote the expression of PAX5 and the progression of ccRCC, and such regulation can be salvaged by miR-532-3p inhibitor. CONCLUSION: A novel positive feedback loop, PAX5/circSOD2/miR-532-3p/PAX5 was identified in the study, indicating that the loop may play an important role in the diagnosis and prognostic prediction in ccRCC patients.

Asunto(s)

Carcinoma de Células Renales , Proliferación Celular , Retroalimentación Fisiológica , Regulación Neoplásica de la Expresión Génica , Neoplasias Renales , MicroARNs , ARN Circular , Humanos , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/metabolismo , ARN Circular/genética , ARN Circular/metabolismo , Neoplasias Renales/genética , Neoplasias Renales/patología , Neoplasias Renales/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Línea Celular Tumoral , Proliferación Celular/genética , Femenino , Persona de Mediana Edad , Masculino , Carcinogénesis/genética , Carcinogénesis/patología , Movimiento Celular/genética , Factor de Transcripción PAX5/metabolismo , Factor de Transcripción PAX5/genética , Oncogenes/genética , Secuencia de Bases , Progresión de la Enfermedad , Invasividad Neoplásica , Reproducibilidad de los Resultados

RESUMEN

A new Mg-4Zn X Ti-6Al-4V (TC4, of 0, 1, and 3 wt.%) alloy was successfully fabricated by a simple and low-cost gravity casting method and heat treatment at 150 °C for 24 h. The composite was examined by XRD, uniaxial tests, FESEM/EDS, potentiostat/EIS, and immersion tests for the material's microstructures, mechanical properties, electrochemical characteristics, and corrosion resistance. Experimental results indicate that heat treatment enables the precipitation of Zn along the Mg grain boundaries and drives the co-precipitation of Al around the TC4 particles and nearby grain boundaries. Uniaxial tensile tests reveal that TC4 reinforces the Mg-Zn matrix material with higher elastic modulus, ultimate tensile stress, and toughness. The heat treatment further enhanced these mechanical properties. Electrochemical tests show that 1 wt.% TC4 composite exhibits the highest open circuit potential among all tested samples, which implies the 1 wt.% TC4-added Mg-Zn is better resistant to the oxidation of the essential metals Mg, Zn, and Al. The immersion tests in the HBSS solution further show that the 1 wt.% TC4 composite has the lowest rise of pH values after 14 days, and EDS for the corroded surface signifies that Mg is the main element vulnerable to oxidation by corrosion.

RESUMEN

Reducing energy consumption in conventional nitrogen removal processes is a crucial and urgent requirement. This study proposes an efficient electrode-dependent bio-electrochemical anaerobic ammonium (NH4+-N) oxidation (BE-ANAMMOX) process, employing a carbon brush as the electron acceptor and voltage of 0.8 V. The applied voltage facilitated the removal of NH4+-N with a maximum removal efficiency of 41% and a Coulombic efficiency of 40.92%, without the addition of nitrite (NO2--N). Furthermore, the NH4+-N removal efficiency demonstrated an increase corresponding to the increase in the anodic surface area. The bio-electrochemical NH4+-N removal achieved remarkable reductions, eliminating the need for O2 and NO2--N by 100%, lowering energy consumption by 67%, and reducing CO2 emissions by 66% when treating 1 kg of NH4+-N. An analysis of the microbial community revealed an increase in nitrifiers and denitrifiers, including Exiguobacterium aestuarii, Alishewanella aestuarii, Comamonas granuli, and Acinetobacter baumannii. This intricate process involved the direct conversion of NH4+-N to N2 by ANAMMOX bacteria through extracellular electron transfer, all without NO2--N. Thus, bio-electrochemical NH4+-N removal exhibits promising potential for effective nitrogen removal in wastewater treatment facilities.

Asunto(s)

Compuestos de Amonio , Nitritos , Dióxido de Nitrógeno , Desnitrificación , Anaerobiosis , Reactores Biológicos/microbiología , Oxidación-Reducción , Nitrógeno

RESUMEN

This study aimed to identify the related substances of phloroglucinol injection by two-dimensional liquid chromatography quadrupole time-of-flight mass spectrometry (2D-LC-Q-TOF/MS). The first-dimensional separation was carried out on an HSS T3 (250 mm × 4.6 mm, 5 μm) column by gradient elution using 1.36 g·L-1 potassium dihydrogen phosphate buffer solution (pH adjusted to 3.0 with diluted phosphoric acid) and acetonitrile as the mobile phases. The separated components were then trapped in switch valve tube lines respectively and delivered to the second-dimensional desalting gradient elution which was performed with a BDS C18 (100 mm × 4.6 mm, 2.4 μm) column using 0.1% formic acid and methanol as the mobile phases. After rapid desalting, electrospray-ionization quadrupole time-of-flight high resolution mass spectrometry was used for determining the accurate masses and elemental compositions of the parents and their product ions for both phloroglucinol and its related substance. Structures of the related substances were then figured out by mass spectrometry elucidation, organic reaction mechanism analysis, and/or comparison with reference substances. Under the established analytical conditions, phloroglucinol and its related substances were adequately separated, 17 main related substances were detected and identified in the injection and its stressed samples for the first time. The identification results can provide reference for the quality control of phloroglucinol injection.

RESUMEN

Metabolic fitness of T cells is essential for their vitality, which is largely dependent on the behavior of the mitochondria. The nature of mitochondrial behavior in tumor-infiltrating T cells remains poorly understood. In this study, we show that mitofusin-2 (MFN2) expression is positively correlated with the prognosis of multiple cancers. Genetic ablation of Mfn2 in CD8+ T cells dampens mitochondrial metabolism and function and promotes tumor progression. In tumor-infiltrating CD8+ T cells, MFN2 enhances mitochondria-endoplasmic reticulum (ER) contact by interacting with ER-embedded Ca2+-ATPase SERCA2, facilitating the mitochondrial Ca2+ influx required for efficient mitochondrial metabolism. MFN2 stimulates the ER Ca2+ retrieval activity of SERCA2, thereby preventing excessive mitochondrial Ca2+ accumulation and apoptosis. Elevating mitochondria-ER contact by increasing MFN2 in CD8+ T cells improves the efficacy of cancer immunotherapy. Thus, we reveal a tethering-and-buffering mechanism of organelle cross-talk that regulates the metabolic fitness of tumor-infiltrating CD8+ T cells and highlights the therapeutic potential of enhancing MFN2 expression to optimize T cell function.

Asunto(s)

Linfocitos T CD8-positivos , Neoplasias , Humanos , Apoptosis , Retículo Endoplásmico , GTP Fosfohidrolasas , Mitocondrias , Proteínas Mitocondriales

RESUMEN

BACKGROUND: Improved markers for predicting recurrence are needed to stratify patients with localised (stage I-III) renal cell carcinoma after surgery for selection of adjuvant therapy. We developed a novel assay integrating three modalities-clinical, genomic, and histopathological-to improve the predictive accuracy for localised renal cell carcinoma recurrence. METHODS: In this retrospective analysis and validation study, we developed a histopathological whole-slide image (WSI)-based score using deep learning allied to digital scanning of conventional haematoxylin and eosin-stained tumour tissue sections, to predict tumour recurrence in a development dataset of 651 patients with distinctly good or poor disease outcome. The six single nucleotide polymorphism-based score, which was detected in paraffin-embedded tumour tissue samples, and the Leibovich score, which was established using clinicopathological risk factors, were combined with the WSI-based score to construct a multimodal recurrence score in the training dataset of 1125 patients. The multimodal recurrence score was validated in 1625 patients from the independent validation dataset and 418 patients from The Cancer Genome Atlas set. The primary outcome measured was the recurrence-free interval (RFI). FINDINGS: The multimodal recurrence score had significantly higher predictive accuracy than the three single-modal scores and clinicopathological risk factors, and it precisely predicted the RFI of patients in the training and two validation datasets (areas under the curve at 5 years: 0·825-0·876 vs 0·608-0·793; p<0·05). The RFI of patients with low stage or grade is usually better than that of patients with high stage or grade; however, the RFI in the multimodal recurrence score-defined high-risk stage I and II group was shorter than in the low-risk stage III group (hazard ratio [HR] 4·57, 95% CI 2·49-8·40; p<0·0001), and the RFI of the high-risk grade 1 and 2 group was shorter than in the low-risk grade 3 and 4 group (HR 4·58, 3·19-6·59; p<0·0001). INTERPRETATION: Our multimodal recurrence score is a practical and reliable predictor that can add value to the current staging system for predicting localised renal cell carcinoma recurrence after surgery, and this combined approach more precisely informs treatment decisions about adjuvant therapy. FUNDING: National Natural Science Foundation of China, and National Key Research and Development Program of China.

Asunto(s)

Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/diagnóstico , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Pronóstico , Estudios Retrospectivos , Biomarcadores de Tumor , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Neoplasias Renales/diagnóstico , Neoplasias Renales/genética , Neoplasias Renales/patología

RESUMEN

Clear cell Renal Cell Carcinoma (ccRCC) is a highly heterogeneous disease, making it challenging to predict prognosis and therapy efficacy. In this study, we aimed to explore the role of 5-methylcytosine (m5C) RNA modification in ccRCC and its potential as a predictor for therapy response and overall survival (OS). We established a novel 5-methylcytosine RNA modification-related gene index (M5CRMRGI) and studied its effect on the tumor microenvironment (TME) using single-cell sequencing data for in-depth analysis, and verified it using spatial sequencing data. Our results showed that M5CRMRGI is an independent predictor of OS in multiple datasets and exhibited outstanding performance in predicting the OS of ccRCC. Distinct mutation profiles, hallmark pathways, and infiltration of immune cells in TME were observed between high- and low-M5CRMRGI groups. Single-cell/spatial transcriptomics revealed that M5CRMRGI could reprogram the distribution of tumor-infiltrating immune cells. Moreover, significant differences in tumor immunogenicity and tumor immune dysfunction and exclusion (TIDE) were observed between the two risk groups, suggesting a better response to immune checkpoint blockade therapy of the high-risk group. We also predicted six potential drugs binding to the core target of the M5CRMRGI signature via molecular docking. Real-world treatment cohort data proved once again that high-risk patients were appropriate for immune checkpoint blockade therapy, while low-risk patients were appropriate for Everolimus. Our study shows that the m5C modification landscape plays a role in TME distribution. The proposed M5CRMRGI-guided strategy for predicting survival and immunotherapy efficacy, we reported here, might also be applied to more cancers other than ccRCC.

RESUMEN

Background: Renal clear cell carcinoma (ccRCC) is one of the most prevailing type of malignancies, which is affected by chemokines. Chemokines can form a local network to regulate the movement of immune cells and are essential for tumor proliferation and metastasis as well as for the interaction between tumor cells and mesenchymal cells. Establishing a chemokine genes signature to assess prognosis and therapy responsiveness in ccRCC is the goal of this effort. Methods: mRNA sequencing data and clinicopathological data on 526 individuals with ccRCC were gathered from the The Cancer Genome Atlas database for this investigation (263 training group samples and 263 validation group samples). Utilizing the LASSO algorithm in conjunction with univariate Cox analysis, the gene signature was constructed. The Gene Expression Omnibus (GEO) database provided the single cell RNA sequencing (scRNA-seq) data, and the R package "Seurat" was applied to analyze the scRNA-seq data. In addition, the enrichment scores of 28 immune cells in the tumor microenvironment (TME) were calculated using the "ssGSEA" algorithm. In order to develop possible medications for patients with high-risk ccRCC, the "pRRophetic" package is employed. Results: High-risk patients had lower overall survival in this model for predicting prognosis, which was supported by the validation cohort. In both cohorts, it served as an independent prognostic factor. Annotation of the predicted signature's biological function revealed that it was correlated with immune-related pathways, and the riskscore was positively correlated with immune cell infiltration and several immune checkpoints (ICs), including CD47, PDCD1, TIGIT, and LAG-3, while it was negatively correlated with TNFRSF14. The CXCL2, CXCL12, and CX3CL1 genes of this signature were shown to be significantly expressed in monocytes and cancer cells, according to scRNA-seq analysis. Furthermore, the high expression of CD47 in cancer cells suggested us that this could be a promising immune checkpoint. For patients who had high riskscore, we predicted 12 potential medications. Conclusion: Overall, our findings show that a putative 7-chemokine-gene signature might predict a patient's prognosis for ccRCC and reflect the disease's complicated immunological environment. Additionally, it offers suggestions on how to treat ccRCC using precision treatment and focused risk assessment.

RESUMEN

LZTFL1 is a tumor suppressor located in chromosomal region 3p21.3 that is deleted frequently and early in various cancer types including the kidney cancer. However, its role in kidney tumorigenesis remains unknown. Here we hypothesized a tumor suppressive function of LZTFL1 in clear cell renal cell carcinoma (ccRCC) and its mechanism of action based on extensive bioinformatics analysis of patients' tumor data and validated it using both gain- and loss-functional studies in kidney tumor cell lines and patient-derive xenograft (PDX) model systems. Our studies indicated that LZTFL1 inhibits kidney tumor cell proliferation by destabilizing AKT through ZNRF1-mediated ubiquitin proteosome pathway and inducing cell cycle arrest at G1. Clinically, we found that LZTFL1 is frequently deleted in ccRCC. Downregulation of LZTFL1 is associated with a poor ccRCC outcome and may be used as prognostic maker. Furthermore, we show that overexpression of LZTFL1 in PDX via lentiviral delivery suppressed PDX growth, suggesting that re-expression of LZTFL1 may be a therapeutic strategy against ccRCC.

Asunto(s)

Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/patología , Línea Celular Tumoral , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Neoplasias Renales/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Factores de Transcripción/metabolismo , Ubiquitinas/metabolismo

RESUMEN

Epigenetics is an emerging mechanism for tumorigenesis. Treatment that targets epigenetic regulators is becoming an attractive strategy for cancer therapy. The role of epigenetic therapy in prostate cancer (PCa) remains elusive. Previously we demonstrated that upregulation of histone lysine demethylase KDM4B correlated with the appearance of castration resistant prostate cancer (CRPC) and identified a small molecular inhibitor of KDM4B, B3. In this study, we further investigated the role of KDM4B in promoting PCa progression and tested the efficacy of B3 using clinically relevant PCa models including PCa cell line LNCaP and 22Rv1 and xenografts derived from these cell lines. In loss and gain-functional studies of KDM4B in PCa cells, we found that overexpression of KDM4B in LNCaP cells enhanced its tumorigenicity whereas knockdown of KDM4B in 22Rv1 cells reduced tumor growth in castrated mice. B3 suppressed the growth of 22Rv1 xenografts and sensitized tumor to anti-androgen receptor (AR) antagonist enzalutamide inhibition. B3 also inhibited 22Rv1 tumor growth synergistically with rapamycin, leading to cell apoptosis. Comparative transcriptomic analysis performed on KDM4B knockdown and B3-treated 22Rv1 cells revealed that B3 inhibited both H3K9me3 and H3K27me3 demethylase activities. Our studies establish KDM4B as a target for CRPC and B3 as a potential therapeutic agent. B3 as monotherapy or in combination with other anti-PCa therapeutics offers proof of principle for the clinical translation of epigenetic therapy targeting KDMs for CRPC patients.

Asunto(s)

Neoplasias de la Próstata Resistentes a la Castración , Masculino , Humanos , Animales , Ratones , Neoplasias de la Próstata Resistentes a la Castración/patología , Receptores Androgénicos/metabolismo , Histona Demetilasas , Línea Celular Tumoral , Antagonistas de Andrógenos/farmacología , Proliferación Celular , Histona Demetilasas con Dominio de Jumonji/metabolismo

RESUMEN

Background: Tuberculosis (TB) outbreaks in schools present a public health challenge. In order to effectively control the spread of transmission, timely screening, accurate diagnosis and comprehensive epidemiological investigations are essential. Methods: In July 2021, a TB outbreak occurred in a junior high school in Y City, Zhejiang Province. Students and faculty were screened for TB by symptom screening, chest radiography, and tuberculin skin test during four rounds of contact screenings. For sputum smear-negative and sputum-scarce patients, bronchoscopy was used to collect BAL samples for Xpert Mycobacterium tuberculosis/rifampin (MTB/RIF). Whole-genome sequencing and bioinformatics analysis were performed on isolates to identify the strains of MTB isolates and predict drug resistance. Results: Between July 2021 and November 2021, a total of 1,257 students and faculty were screened for TB during screenings. A total of 15 students (1.2% of persons screened) aged 15 years were diagnosed with TB. Eighty percent (12/15) of the cases were laboratory-confirmed (10/12 [83%] Xpert MTB/RIF-positive, 2/12 [17%] culture-positive). Most cases (12/15 [80%]) were in students from Class 2. All cases were asymptomatic except for the index case who had symptoms for more than two months. Seven MTB isolates were collected and belonged to lineage 2. Conclusion: Our findings demonstrated the potential of Xpert MTB/RIF using BAL as a screening tool in school TB outbreaks for sputum smear-negative and sputum-sparse suspects, which may not only rapidly improves diagnostic accuracy, but also facilitates epidemiological investigations and homology analysis.

Asunto(s)

Rifampin , Tuberculosis , Humanos , Líquido del Lavado Bronquioalveolar , Tuberculosis/diagnóstico , Tuberculosis/epidemiología , Brotes de Enfermedades , China/epidemiología , Instituciones Académicas

RESUMEN

Millions of Norway rats (Rattus norvegicus)inhabit New York City (NYC), presenting the potential for transmission of SARS-CoV-2 from humans to rats and other wildlife. We evaluated SARS-CoV-2 exposure among 79 rats captured from NYC during the fall of 2021. Results showed that 13 of 79 rats (16.5%) tested IgG or IgM positive, and partial genomes of SARS-CoV-2 were recovered from four rats that were qRT-PCR positive. Using a virus challenge study, we also showed that Alpha, Delta, and Omicron variants can cause robust infections in wild-type Sprague Dawley (SD) rats, including high level replications in the upper and lower respiratory tracts and induction of both innate and adaptive immune responses. Additionally, the Delta variant resulted in the highest infectivity. In summary, our results indicated that rats are susceptible to infection with Alpha, Delta, and Omicron variants, and rats in the NYC municipal sewer systems have been exposed to SARS-CoV-2. Our findings highlight the potential risk of secondary zoonotic transmission from urban rats and the need for further monitoring of SARS-CoV-2 in those populations. ImportanceSince its emergence causing the COVID-19 pandemic, the host tropism expansion of SARS-CoV-2 raises a potential risk for reverse-zoonotic transmission of emerging variants into rodent species, including wild rat species. In this study, we presented both genetic and serological evidence for SARS-CoV-2 exposure in wild rat population from New York City, and these viruses are potentially linked to the viruses during the early stages of the pandemic. We also demonstrated that rats are susceptible to additional variants (i.e., Alpha, Delta, and Omicron) predominant in humans and that the susceptibility to different variants vary. Our findings highlight the potential risk of secondary zoonotic transmission from urban rats and the need for further monitoring of SARS-CoV-2 in those populations.

RESUMEN

BACKGROUND: N6-methyladenosine (m6A) related long noncoding RNAs (lncRNAs) may have prognostic value in bladder cancer for their key role in tumorigenesis and innate immunity. METHODS: Bladder cancer transcriptome data and the corresponding clinical data were acquired from the Cancer Genome Atlas (TCGA) database. The m6A-immune-related lncRNAs were identified using univariate Cox regression analysis and Pearson correlation analysis. A risk model was established using least absolute shrinkage and selection operator (LASSO) Cox regression analyses, and analyzed using nomogram, time-dependent receiver operating characteristics (ROC) and Kaplan-Meier survival analysis. The differences in infiltration scores, clinical features, and sensitivity to Talazoparib of various immune cells between low- and high-risk groups were investigated. RESULTS: Totally 618 m6A-immune-related lncRNAs and 490 immune-related lncRNAs were identified from TCGA, and 47 lncRNAs of their intersection demonstrated prognostic values. A risk model with 11 lncRNAs was established by Lasso Cox regression, and can predict the prognosis of bladder cancer patients as demonstrated by time-dependent ROC and Kaplan-Meier analysis. Significant correlations were determined between risk score and tumor malignancy or immune cell infiltration. Meanwhile, significant differences were observed in tumor mutation burden and stemness-score between the low-risk group and high-risk group. Moreover, high-risk group patients were more responsive to Talazoparib. CONCLUSIONS: An m6A-immune-related lncRNA risk model was established in this study, which can be applied to predict prognosis, immune landscape and chemotherapeutic response in bladder cancer.

Asunto(s)

ARN Largo no Codificante , Neoplasias de la Vejiga Urinaria , Humanos , Pronóstico , ARN Largo no Codificante/genética , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología , Regulación Neoplásica de la Expresión Génica , Biomarcadores de Tumor/genética

RESUMEN

Circular RNAs (circRNAs) play critical roles in clear cell renal cell carcinoma (ccRCC). However, their involvement in sunitinib resistance remains largely unknown. Herein, we identified a novel circRNA, named circME1, which contributes to sunitinib resistance development in ccRCC. CircME1 also promoted proliferation, migration, and invasion of ccRCC cells. Further mechanism analysis showed that circME1 interacted with U1 snRNP at the promoter of its parental gene ME1, thereby upregulating the expression of ME1, enhancing aerobic glycolysis of ccRCC, and promoting its malignant phenotype. Furthermore, ME1 specific inhibitor could effectively repress the oncogenic functions of circME1. Taken together, our study demonstrates that the circME1/ME1 pathway is involved in ccRCC progression and sunitinib resistance development, which may be exploited for anticancer therapy.

Asunto(s)

Carcinoma de Células Renales , Neoplasias Renales , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/metabolismo , Línea Celular Tumoral , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Glucólisis/genética , Humanos , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/genética , Neoplasias Renales/metabolismo , ARN Circular , Sunitinib/farmacología

RESUMEN

Background: The aim of this study was to identify the ferroptosis induced tumor microenvironment (FeME) landscape in bladder cancer (BCa) for mRNA vaccine development and selecting suitable patients for precision treatment. Methods: Gene expression profiles and clinical information of 1216 BCa patients were extracted from TCGA-BLCA, three GEO databases and IMvigor210 cohort. We comprehensively established the FeME landscape of 1216 BCa samples based on 290 ferroptosis related genes (FRGs), and systematically correlated these regulation patterns with TME cell-infiltrating characteristics. Besides, we identified the patients' ferroptosis risk index (FRI) to predict the prognosis of BCa for precise treatment. Results: Six over-expressed and mutated tumor antigens associated with poor prognosis and infiltration of antigen presenting cells were identified in BCa. Furthermore, we demonstrated the evaluation of FeME within individual tumors could predict stages of tumor inflammation, subtypes, genetic variation, and patient prognosis. Then, 5-lncRNA signature was mined to produce the FRI. Low FRI was also linked to increased mutation load, better prognosis and enhanced response to anti-PD-L1 immunotherapy. Besides, an immunotherapy cohort confirmed patients with lower FRI demonstrated significant therapeutic advantages and clinical benefits. Conclusions: TFRC, SCD, G6PD, FADS2, SQLE, and SLC3A2 are potent antigens for developing anti-BCa mRNA vaccine. Establishment of FRI will contribute to enhancing our cognition of TME infiltration characterization and guiding more effective immunotherapy strategies and selecting appropriate patients for tumor vaccine therapy. Supplementary Information: The online version contains supplementary material available at 10.1186/s40537-022-00641-z.

RESUMEN

Idiopathic asthenozoospermia, a common factor in male infertility, is characterized by altered sperm motility function in fresh ejaculate. Although the ß-defensin 126 (DEFB126) protein is associated with asthenozoospermia, DEFB126 gene polymorphisms have not been extensively studied. Therefore, the association between DEFB126 gene polymorphisms and asthenozoospermia requires further investigation. Screening was performed by semen analysis, karyotype analysis, and Y microdeletion detection, and 102 fertile men and 106 men with asthenozoospermia in Chengdu, China, were selected for DEFB126 gene sequence analyses. Seven nucleotide mutations and two nucleotide deletions in the DEFB126 gene were detected. rs11467417 (317-318 del/del), rs11467497 (163-166 wt/del), c.152T>C, and c.227A>G were significantly different between the control and asthenozoospermia groups, likely representing high-risk genetic factors for asthenozoospermia among males. DEFB126 expression was not observed in sperm with rs11467497 homozygous deletion and was unstable in sperm with rs11467417 homozygous deletion. The rs11467497 four-nucleotide deletion leads to truncation of DEFB126 at the carboxy-terminus, and the rs11467417 binucleotide deletion produces a non-stop messenger RNA (mRNA). The above deletions may be responsible for male hypofertility and infertility by reducing DEFB126 affinity to sperm surfaces. Based on in silico analysis, the amino acids 51M and 76K are located in the highly conserved domain; c.152T>C (M51T) and c.227A>G (K76R) are predicted to be damaging and capable of changing alternative splice, structural and posttranslational modification sites of the RNA, as well as the secondary structure, structural stability, and hydrophobicity of the protein, suggesting that these mutations are associated with asthenozoospermia.

Asunto(s)

Astenozoospermia , beta-Defensinas , Masculino , Humanos , Astenozoospermia/genética , Astenozoospermia/metabolismo , Motilidad Espermática/genética , Homocigoto , Polimorfismo de Nucleótido Simple , Semen , Eliminación de Secuencia/genética , Espermatozoides/metabolismo , Nucleótidos/metabolismo , beta-Defensinas/genética , beta-Defensinas/metabolismo