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1.
World J Clin Cases ; 12(22): 5245-5252, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39109047

RESUMEN

BACKGROUND: Gout and seronegative rheumatoid arthritis (SNRA) are two distinct inflammatory joint diseases whose co-occurrence is relatively infrequently reported. Limited information is available regarding the clinical management and prognosis of these combined diseases. CASE SUMMARY: A 57-year-old woman with a 20-year history of joint swelling, tenderness, and morning stiffness who was negative for rheumatoid factor and had a normal uric acid level was diagnosed with SNRA. The initial regimen of methotrexate, leflunomide, and celecoxib alleviated her symptoms, except for those associated with the knee. After symptom recurrence after medication cessation, her regimen was updated to include iguratimod, methotrexate, methylprednisolone, and folic acid, but her knee issues persisted. Minimally invasive needle-knife scope therapy revealed proliferating pannus and needle-shaped crystals in the knee, indicating coexistent SNRA and atypical knee gout. After postarthroscopic surgery to remove the synovium and urate crystals, and following a tailored regimen of methotrexate, leflunomide, celecoxib, benzbromarone, and allopurinol, her knee symptoms were significantly alleviated with no recurrence observed over a period of more than one year, indicating successful management of both conditions. CONCLUSION: This study reports the case of a patient concurrently afflicted with atypical gout of the knee and SNRA and underscores the significance of minimally invasive joint techniques as effective diagnostic and therapeutic tools in the field of rheumatology and immunology.

2.
Sci Total Environ ; : 175415, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39128514

RESUMEN

The atrazine (ATR) is extensively used in dryland crops like corn and sorghum in black soil region of Northeast China, posing ecological risks due to toxic metabolites. Vermicompost are known for soil organic pollution remediation but their role in pesticide degradation in black soil remains understudied. The influence of vermicompost on the microbial degradation pathway of atrazine was assessed in this study. Although vermicompost didn't significantly boost atrazine removal, they notably aided in primary metabolite degradation, hydroxyatrazine (HYA), deisopropylatrazine (DIA), and deethylatrazine (DEA), reducing their content by 38.67 %. They also altered the soil microbial community structure, favoring atrazine-degrading bacteria like Proteobacteria, Firmicutes, and Actinobacteria. Five secondary degradation products were identified in vermicompost treatments. Atrazine degradation occurred via dechlorination, dealkylation, and deamination pathways mainly by Nocardioidacea, Streptomycetaceae, Bacillaceae, Sphingomonadaceae, Comamonadaceae and Nitrososphaeraceae. pH and available nitrogen (AN) influenced microbial community structure and atrazine degradation, correlating with vermicompost application rates. Future black soil remediation should optimize application rates based on atrazine content and soil properties.

3.
Environ Sci Technol ; 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39133145

RESUMEN

In the pursuit of carbon neutrality, China's 2060 targets have been largely anchored in reducing greenhouse gas emissions, with less emphasis on the consequential benefits for air quality and public health. This study pivots to this critical nexus, exploring how China's carbon neutrality aligns with the World Health Organization's air quality guidelines (WHO AQG) regarding fine particulate matter (PM2.5) exposure. Coupling a technology-rich integrated assessment model, an emission-concentration response surface model, and exposure and health assessment, we find that decarbonization reduces sulfur dioxide (SO2), nitrogen oxides (NOx), and PM2.5 emissions by more than 90%; reduces nonmethane volatile organic compounds (NMVOCs) by more than 50%; and simultaneously reduces the disparities across regions. Critically, our analysis reveals that further targeted reductions in air pollutants, notably NH3 and non-energy-related NMVOCs, could bring most Chinese cities into attainment of WHO AQG for PM2.5 5 to 10 years earlier than the pathway focused solely on carbon neutrality. Thus, the integration of air pollution control measures into carbon neutrality strategies will present a significant opportunity for China to attain health and environmental equality.

4.
Asian J Surg ; 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39117541

RESUMEN

Lung cancer is a leading cause of cancer-related mortality worldwide, profoundly affecting patients' quality of life. Patient-reported outcomes (PROs) provide essential insights from the patients' perspective, a crucial aspect often overlooked by traditional clinical outcomes. This review synthesizes research on the role of PROs in lung cancer surgery to enhance patient care and outcomes. We conducted a comprehensive literature search across PubMed, Scopus, and Web of Science up to March 2024, using terms such as "lung cancer," "Patient Reported Outcome," "lobectomy," "segmentectomy," and "lung surgery." The criteria included original studies on lung cancer patients who underwent surgical treatment and reported on PROs. After screening and removing duplicates, reviews, non-English articles, and irrelevant studies, 36 research articles were selected, supported by an additional 53 publications, totaling 89 references. The findings highlight the utility of PROs in assessing post-surgical outcomes, informing clinical decisions, and facilitating patient-centered care. However, challenges in standardization, patient burden, and integration into clinical workflows remain, underscoring the need for further research and methodological refinement. PROs are indispensable for understanding the quality-of-life post-surgery and enhancing communication and decision-making in clinical practice. Their integration into routine care is vital for a holistic approach to lung cancer treatment, promising significant improvements in patient outcomes and quality of care.

5.
Cells ; 13(13)2024 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-38995009

RESUMEN

We developed an automated microregistration method that enables repeated in vivo skin microscopy imaging of the same tissue microlocation and specific cells over a long period of days and weeks with unprecedented precision. Applying this method in conjunction with an in vivo multimodality multiphoton microscope, the behavior of human skin cells such as cell proliferation, melanin upward migration, blood flow dynamics, and epidermal thickness adaptation can be recorded over time, facilitating quantitative cellular dynamics analysis. We demonstrated the usefulness of this method in a skin biology study by successfully monitoring skin cellular responses for a period of two weeks following an acute exposure to ultraviolet light.


Asunto(s)
Piel , Humanos , Piel/citología , Piel/diagnóstico por imagen , Rayos Ultravioleta , Rastreo Celular/métodos , Proliferación Celular , Movimiento Celular , Microscopía de Fluorescencia por Excitación Multifotónica/métodos , Microscopía/métodos
6.
Toxicon ; 247: 107843, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-38964621

RESUMEN

BACKGROUND: Taiwan habu (Protobothrops mucrosquamatus), green bamboo viper (Viridovipera stejnegeri), and Taiwan cobra (Naja atra) are the most venomous snakebites in Taiwan. Patients commonly present with limb swelling but misdiagnosis rates are high, and currently available diagnostic tools are limited. This study explores the immune responses in snakebite patients to aid in differential diagnosis. METHODS: This prospective observational study investigated the changes in cytokines in snakebite patients and their potential for diagnosis. RESULTS: Elevated pro-inflammatory cytokines IL-6 and TNF-α were observed in all snakebite patients compared to the healthy control group. While no significant disparities were observed in humoral immune response cytokines, there were significant differences in IFN-γ levels, with significantly higher IL-10 levels in patients bitten by cobras. Patients with TNF-α levels exceeding 3.02 pg/mL were more likely to have been bitten by a cobra. CONCLUSION: This study sheds light on the immune responses triggered by various venomous snakebites, emphasizing the potential of cytokine patterns for snakebite-type differentiation. Larger studies are needed to validate these findings for clinical use, ultimately improving snakebite diagnosis and treatment.


Asunto(s)
Citocinas , Mordeduras de Serpientes , Humanos , Taiwán , Animales , Citocinas/sangre , Estudios Prospectivos , Adulto , Masculino , Persona de Mediana Edad , Femenino , Factor de Necrosis Tumoral alfa , Viperidae , Interleucina-6/sangre , Anciano
7.
Nano Lett ; 24(29): 8887-8893, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-38984749

RESUMEN

The synthesis of transition metal nitrides nanocrystals (TMNs NCs) has posed a significant challenge due to the limited reactivity of nitrogen sources at lower temperatures and the scarcity of available synthesis methods. In this study, we present a novel colloidal synthesis strategy for the fabrication of Cu3N nanorods (NRs). It is found that the trace oxygen (O2) plays an important role in the synthesis process. And a new mechanism for the formation of Cu3N is proposed. Subsequently, by employing secondary lateral epitaxial growth, the Cu3N-Cu2O heteronanostructures (HNs) can be prepared. The Cu3N NRs and Cu3N-Cu2O HNs were evaluated as precursor electrocatalysts for the CO2 reduction reaction (CO2RR). The Cu3N-Cu2O HNs demonstrate remarkable selectivity and stability with ethylene (C2H4) Faradaic efficiency (FE) up to 55.3%, surpassing that of Cu3N NRs. This study provides innovative insights into the reaction mechanism of colloidal synthesis of TMNs NCs and presents alternative options for designing cost-effective electrocatalysts to achieve carbon neutrality.

9.
Aquat Toxicol ; 273: 107015, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38996482

RESUMEN

Nitrite, a highly toxic environmental contaminant, induces various physiological toxicities in aquatic animals. Herein, we investigate the in vivo effects of nitrite exposure at concentrations of 0, 0.2, 2, and 20 mg/L on glucose and lipid metabolism in zebrafish. Our results showed that exposure to nitrite induced mitochondrial oxidative stress in zebrafish liver and ZFL cells, which were evidenced by increased levels of malondialdehyde (MDA) and reactive oxygen species (ROS) as well as decreased mitochondrial membrane potential (MMP) and adenosine triphosphate (ATP). Changes in these oxidative stress markers were accompanied by alterations in the expression levels of genes involved in HIF-1α pathway (hif1α and phd), which subsequently led to the upregulation of glycolysis and gluconeogenesis-related genes (gk, pklr, pdk1, pepck, g6pca, ppp1r3cb, pgm1, gys1 and gys2), resulting in disrupted glucose metabolism. Moreover, nitrite exposure activated ERs (Endoplasmic Reticulum stress) responses through upregulating of genes (atf6, ern1 and xbp1s), leading to increased expression of lipolysis genes (pparα, cpt1aa and atgl) and decreased expression of lipid synthesis genes (srebf1, srebf2, fasn, acaca, scd, hmgcra and hmgcs1). These results were also in consistent with the observed changes in glycogen, lactate and decreased total triglyceride (TG) and total cholesterol (TC) in the liver of zebrafish. Our in vitro results showed that co-treatment with Mito-TEMPO and nitrite attenuated nitrite-induced oxidative stress and improved mitochondrial function, which were indicated by the restorations of ROS, MMP, ATP production, and glucose-related gene expression recovered. Co-treatment of TUDCA and nitrite prevented nitrite-induced ERs response and which was proved by the levels of TG and TC ameliorated as well as the expression levels of lipid metabolism-related genes. In conclusion, our study suggested that nitrite exposure disrupted hepatic glucose and lipid metabolism through mitochondrial dysfunction and ERs responses. These findings contribute to the understanding of the potential hepatotoxicity for aquatic animals in the presence of ambient nitrite.


Asunto(s)
Estrés del Retículo Endoplásmico , Glucosa , Metabolismo de los Lípidos , Hígado , Nitritos , Estrés Oxidativo , Contaminantes Químicos del Agua , Pez Cebra , Animales , Glucosa/metabolismo , Nitritos/toxicidad , Hígado/efectos de los fármacos , Hígado/metabolismo , Estrés del Retículo Endoplásmico/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad , Metabolismo de los Lípidos/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Trastornos del Metabolismo de los Lípidos/inducido químicamente , Trastornos del Metabolismo de los Lípidos/genética
10.
Zool Res ; 45(4): 833-844, 2024 07 18.
Artículo en Inglés | MEDLINE | ID: mdl-39004861

RESUMEN

Porcine reproductive and respiratory syndrome (PRRS) is a globally prevalent contagious disease caused by the positive-strand RNA PRRS virus (PRRSV), resulting in substantial economic losses in the swine industry. Modifying the CD163 SRCR5 domain, either through deletion or substitution, can eff1ectively confer resistance to PRRSV infection in pigs. However, large fragment modifications in pigs inevitably raise concerns about potential adverse effects on growth performance. Reducing the impact of genetic modifications on normal physiological functions is a promising direction for developing PRRSV-resistant pigs. In the current study, we identified a specific functional amino acid in CD163 that influences PRRSV proliferation. Viral infection experiments conducted on Marc145 and PK-15 CD163 cells illustrated that the mE535G or corresponding pE529G mutations markedly inhibited highly pathogenic PRRSV (HP-PRRSV) proliferation by preventing viral binding and entry. Furthermore, individual viral challenge tests revealed that pigs with the E529G mutation had viral loads two orders of magnitude lower than wild-type (WT) pigs, confirming effective resistance to HP-PRRSV. Examination of the physiological indicators and scavenger function of CD163 verified no significant differences between the WT and E529G pigs. These findings suggest that E529G pigs can be used for breeding PRRSV-resistant pigs, providing novel insights into controlling future PRRSV outbreaks.


Asunto(s)
Antígenos CD , Antígenos de Diferenciación Mielomonocítica , Mutación Puntual , Síndrome Respiratorio y de la Reproducción Porcina , Virus del Síndrome Respiratorio y Reproductivo Porcino , Receptores de Superficie Celular , Animales , Porcinos , Síndrome Respiratorio y de la Reproducción Porcina/genética , Síndrome Respiratorio y de la Reproducción Porcina/virología , Virus del Síndrome Respiratorio y Reproductivo Porcino/fisiología , Virus del Síndrome Respiratorio y Reproductivo Porcino/genética , Antígenos de Diferenciación Mielomonocítica/genética , Antígenos de Diferenciación Mielomonocítica/metabolismo , Antígenos CD/genética , Antígenos CD/metabolismo , Receptores de Superficie Celular/genética , Receptores de Superficie Celular/metabolismo , Animales Modificados Genéticamente/genética , Línea Celular
11.
NPJ Clim Action ; 3(1): 63, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39070178

RESUMEN

Under the next cycle of target setting under the Paris Agreement, countries will be updating and submitting new nationally determined contributions (NDCs) over the coming year. To this end, there is a growing need for the United States to assess potential pathways toward a new, maximally ambitious 2035 NDC. In this study, we use an integrated assessment model with state-level detail to model existing policies from both federal and non-federal actors, including the Inflation Reduction Act, Bipartisan Infrastructure Law, and key state policies, across all sectors and gases. Additionally, we develop a high-ambition scenario, which includes new and enhanced policies from these actors. We find that existing policies can reduce net greenhouse gas (GHG) emissions by 44% (with a range of 37% to 52%) by 2035, relative to 2005 levels. The high-ambition scenario can deliver net GHG reductions up to 65% (with a range of 59% to 71%) by 2035 under accelerated implementation of federal regulations and investments, as well as state policies such as renewable portfolio standards, EV sales targets, and zero-emission appliance standards. This level of reductions would provide a basis for continued progress toward the country's 2050 net-zero emissions goal.

12.
Pharmacol Biochem Behav ; 243: 173827, 2024 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-39038728

RESUMEN

Alcohol-related cognitive impairment (ARCI) is highly prevalent among patients with alcohol abuse and dependence. The pathophysiology of ARCI, pivotal for refined therapeutic approaches, is not fully elucidated, posing a risk of progression to severe neurological sequelae such as Korsakoff's syndrome (KS) and Alcohol-Related Dementia (ARD). This study ventures into the underlying mechanisms of chronic alcohol-induced neurotoxicity, notably glutamate excitotoxicity and cytoskeletal disruption, and explores the therapeutic potential of Memantine, a non-competitive antagonist of the N-methyl-d-aspartate (NMDA) receptor known for its neuroprotective effect against excitotoxicity. Our investigation centers on the efficacy of Memantine in mitigating chronic alcohol-induced cognitive and hippocampal damages in vivo. Male C57BL/6J mice were subjected to 30 % (v/v, 6.0 g/kg) ethanol via intragastric administration alongside Memantine co-treatment (10 mg/kg/day, intraperitoneally) for six weeks. The assessment involved Y maze, Morris water maze, and novel object recognition tests to evaluate spatial and recognition memory deficits. Histopathological evaluations of the hippocampus were conducted to examine the extent of alcohol-induced morphological changes and the potential protective effect of Memantine. The findings reveal that Memantine significantly improves chronic alcohol-compromised cognitive functions and mitigates hippocampal pathological changes, implicating a moderating effect on the disassembly of actin cytoskeleton and microtubules in the hippocampus, induced by chronic alcohol exposure. Our results underscore Memantine's capability to attenuate chronic alcohol-induced cognitive and hippocampal morphological harm may partly through regulating cytoskeleton dynamics, offering valuable insights into innovative therapeutic strategies for ARCI.

13.
Int J Lab Hematol ; 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38874282

RESUMEN

INTRODUCTION: In recent years, the correlation between CD117 antigen and the prognosis of hematological malignancies has been demonstrated. However, there is limited literature on the clinical significance of CD117 antigen in acute promyelocytic leukemia (APL). The aim of this study was to retrospectively analyze the clinical features and prognostic significance of CD117 in APL. METHODS: In this study, we retrospectively investigated the clinicopathological characteristics, outcome, and prognostic impact of negative CD117 expression (CD117-) in 169 APL patients treated with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) containing regimen. RESULTS: The median follow-up period was 63.0 months. CD117- was detected in 13 APL patients (7.7%). No significant differences were found in baseline characteristics between CD117+ and CD117- subgroups. However, compared to CD117+ APL, the incidence of early death (ED) was significantly higher in CD117- APL (p = 0.023). By multivariate analysis, CD117- was an independent adverse prognostic factor for overall survival (OS) and progression-free survival (PFS) (p = 0.022 and p = 0.014, respectively). CONCLUSIONS: To sum up, CD117- is associated with greater risk of ED and has the statistical power to predict inferior OS and PFS, this marker may be considered to build prognostic scores for risk-adapted therapeutic strategies in APL management.

14.
J Am Chem Soc ; 146(27): 18341-18349, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38942067

RESUMEN

Identifying the active phase with the highest activity, which is long-believed to be a steady state of the catalyst, is the basis of rational design of heterogeneous catalysis. In this work, we performed detailed in situ investigations, successfully capturing the instantaneous structure-activity change in oscillating Pd nanocatalysts during methane oxidation, which reveals an unprecedented oscillatory active state. Combining in situ quantitative environmental transmission electron microscopy and highly sensitive online mass spectrometry, we identified two distinct phases for the reaction: one where the Pd nanoparticles refill with oxygen, and the other, a period of abrupt pumping of oxygen and boosted methane oxidation within about 1 s. It is the rapid reduction process that shows the highest activity for total oxidation of methane, not a PdO or Pd steady state under the conditions applied here (methane:oxygen = 5:1). This observation challenges the traditional understanding of the active phase and requires a completely different strategy for catalyst optimization.

15.
Int J Surg ; 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38874490

RESUMEN

BACKGROUND: The impact of resuscitative endovascular balloon occlusion of the aorta (REBOA) on traumatic brain injuries remains uncertain, with potential outcomes ranging from neuroprotection to exacerbation of the injury. The study aimed to evaluate consciousness recovery in patients with blunt trauma with shock and traumatic brain injuries. MATERIAL AND METHODS: Data were obtained from the American College of Surgeons Trauma Quality Improvement Program from 2017-2019. During the study period, 3,138,896 trauma registries were examined, and 16,016 adult patients with blunt trauma, shock, and traumatic brain injuries were included. Among these, 172 (1.1%) underwent REBOA. Comparisons were conducted between patients with and without REBOA after implementing 1:3 propensity score matching to mitigate disparities. The primary outcome was the highest Glasgow Coma Scale score during admission. The secondary outcomes encompassed the volume of blood transfusion, the necessity for hemostatic interventions and therapeutic neurosurgery, and mortality rate. RESULTS: Through well-balanced propensity score matching, a notable difference in mortality rate was observed, with 59.7% in the REBOA group and 48.7% in the non-REBOA group (P=0.015). In the REBOA group, the median 4-hour red blood cell transfusion was significantly higher (2800 mL [1500, 4908] vs. 1300 mL [600, 2500], P<0.001). The REBOA group required lesser hemorrhagic control surgeries (31.8% vs. 47.7%, P<0.001) but needed more transarterial embolization interventions (22.2% vs 15.9%, P=0.076). The incidence of therapeutic neurosurgery was 5.1% in the REBOA group and 8.7% in the non-REBOA group (P=0.168). Among survivors in the REBOA group, the median highest Glasgow Coma Scale score during admission was significantly greater for both total (11 [8, 14] vs. 9 [6, 12], P=0.036) and motor components (6 [4, 6] vs. 5 [3, 6], P=0.037). The highest GCS score among the survivors with predominant pelvic injuries was not different between the two groups (11 [8, 13] vs. 11 [7, 14], P=0.750). CONCLUSIONS: Patients experiencing shock and traumatic brain injury have high mortality rates, necessitating swift resuscitation and prompt hemorrhagic control. The use of REBOA as an adjunct for bridging definitive hemorrhagic control may correlate with enhanced consciousness recovery.

16.
Sensors (Basel) ; 24(12)2024 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-38931679

RESUMEN

In the domain of mobile robot navigation, conventional path-planning algorithms typically rely on predefined rules and prior map information, which exhibit significant limitations when confronting unknown, intricate environments. With the rapid evolution of artificial intelligence technology, deep reinforcement learning (DRL) algorithms have demonstrated considerable effectiveness across various application scenarios. In this investigation, we introduce a self-exploration and navigation approach based on a deep reinforcement learning framework, aimed at resolving the navigation challenges of mobile robots in unfamiliar environments. Firstly, we fuse data from the robot's onboard lidar sensors and camera and integrate odometer readings with target coordinates to establish the instantaneous state of the decision environment. Subsequently, a deep neural network processes these composite inputs to generate motion control strategies, which are then integrated into the local planning component of the robot's navigation stack. Finally, we employ an innovative heuristic function capable of synthesizing map information and global objectives to select the optimal local navigation points, thereby guiding the robot progressively toward its global target point. In practical experiments, our methodology demonstrates superior performance compared to similar navigation methods in complex, unknown environments devoid of predefined map information.

17.
Acta Pharmacol Sin ; 45(7): 1425-1437, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38839936

RESUMEN

Cardiac fibrosis is a pathological scarring process that impairs cardiac function. N-acetyltransferase 10 (Nat10) is recently identified as the key enzyme for the N4-acetylcytidine (ac4C) modification of mRNAs. In this study, we investigated the role of Nat10 in cardiac fibrosis following myocardial infarction (MI) and the related mechanisms. MI was induced in mice by ligation of the left anterior descending coronary artery; cardiac function was assessed with echocardiography. We showed that both the mRNA and protein expression levels of Nat10 were significantly increased in the infarct zone and border zone 4 weeks post-MI, and the expression of Nat10 in cardiac fibroblasts was significantly higher compared with that in cardiomyocytes after MI. Fibroblast-specific overexpression of Nat10 promoted collagen deposition and induced cardiac systolic dysfunction post-MI in mice. Conversely, fibroblast-specific knockout of Nat10 markedly relieved cardiac function impairment and extracellular matrix remodeling following MI. We then conducted ac4C-RNA binding protein immunoprecipitation-sequencing (RIP-seq) in cardiac fibroblasts transfected with Nat10 siRNA, and revealed that angiomotin-like 1 (Amotl1), an upstream regulator of the Hippo signaling pathway, was the target gene of Nat10. We demonstrated that Nat10-mediated ac4C modification of Amotl1 increased its mRNA stability and translation in neonatal cardiac fibroblasts, thereby increasing the interaction of Amotl1 with yes-associated protein 1 (Yap) and facilitating Yap translocation into the nucleus. Intriguingly, silencing of Amotl1 or Yap, as well as treatment with verteporfin, a selective and potent Yap inhibitor, attenuated the Nat10 overexpression-induced proliferation of cardiac fibroblasts and prevented their differentiation into myofibroblasts in vitro. In conclusion, this study highlights Nat10 as a crucial regulator of myocardial fibrosis following MI injury through ac4C modification of upstream activators within the Hippo/Yap signaling pathway.


Asunto(s)
Fibrosis , Ratones Endogámicos C57BL , Infarto del Miocardio , Animales , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Ratones , Masculino , Proteínas Señalizadoras YAP/metabolismo , Fibroblastos/metabolismo , Citidina/análogos & derivados , Citidina/farmacología , Ratones Noqueados , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Acetiltransferasa E N-Terminal/metabolismo , Vía de Señalización Hippo , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Células Cultivadas , Transducción de Señal , Acetiltransferasas N-Terminal/metabolismo , Miocardio/patología , Miocardio/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo
18.
Nat Biotechnol ; 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38862616

RESUMEN

Subclonal reconstruction algorithms use bulk DNA sequencing data to quantify parameters of tumor evolution, allowing an assessment of how cancers initiate, progress and respond to selective pressures. We launched the ICGC-TCGA (International Cancer Genome Consortium-The Cancer Genome Atlas) DREAM Somatic Mutation Calling Tumor Heterogeneity and Evolution Challenge to benchmark existing subclonal reconstruction algorithms. This 7-year community effort used cloud computing to benchmark 31 subclonal reconstruction algorithms on 51 simulated tumors. Algorithms were scored on seven independent tasks, leading to 12,061 total runs. Algorithm choice influenced performance substantially more than tumor features but purity-adjusted read depth, copy-number state and read mappability were associated with the performance of most algorithms on most tasks. No single algorithm was a top performer for all seven tasks and existing ensemble strategies were unable to outperform the best individual methods, highlighting a key research need. All containerized methods, evaluation code and datasets are available to support further assessment of the determinants of subclonal reconstruction accuracy and development of improved methods to understand tumor evolution.

19.
Mol Cell Biochem ; 479(7): 1553-1570, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38856795

RESUMEN

Epigenetics encompasses reversible and heritable chemical modifications of non-nuclear DNA sequences, including DNA and RNA methylation, histone modifications, non-coding RNA modifications, and chromatin rearrangements. In addition to well-studied DNA and histone methylation, RNA methylation has emerged as a hot topic in biological sciences over the past decade. N6-methyladenosine (m6A) is the most common and abundant modification in eukaryotic mRNA, affecting all RNA stages, including transcription, translation, and degradation. Advances in high-throughput sequencing technologies made it feasible to identify the chemical basis and biological functions of m6A RNA. Dysregulation of m6A levels and associated modifying proteins can both inhibit and promote cancer, highlighting the importance of the tumor microenvironment in diverse biological processes. Gastrointestinal tract cancers, including gastric, colorectal, and pancreatic cancers, are among the most common and deadly malignancies in humans. Growing evidence suggests a close association between m6A levels and the progression of gastrointestinal tumors. Global m6A modification levels are substantially modified in gastrointestinal tumor tissues and cell lines compared to healthy tissues and cells, possibly influencing various biological behaviors such as tumor cell proliferation, invasion, metastasis, and drug resistance. Exploring the diagnostic and therapeutic potential of m6A-related proteins is critical from a clinical standpoint. Developing more specific and effective m6A modulators offers new options for treating these tumors and deeper insights into gastrointestinal tract cancers.


Asunto(s)
Adenosina , Neoplasias Gastrointestinales , Humanos , Adenosina/análogos & derivados , Adenosina/metabolismo , Adenosina/genética , Neoplasias Gastrointestinales/genética , Neoplasias Gastrointestinales/patología , Neoplasias Gastrointestinales/metabolismo , ARN Neoplásico/genética , ARN Neoplásico/metabolismo , Epigénesis Genética , Metilación
20.
Ultrasonics ; 142: 107377, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38901151

RESUMEN

The optoacoustic transducer has emerged as a new candidate for medical ultrasound applications and attracts considerable attention. Optoacoustic diagnosis and treatment sometimes require high-intensity acoustic pressure, which is often accompanied by the problem of laser-induced damage. Addressing the laser-induced damage phenomenon from a theoretical perspective holds paramount importance. In this study, the theoretical model of laser-induced damage of the carbon nanotubes-polydimethylsiloxane (CNT-PDMS) composite optoacoustic transducer is established. It is found that this laser-induced damage belongs to thermal ablation damage. Furthermore, the correctness of this theory can be confirmed by experimental results. Most importantly, when the laser energy density is less than threshold value of laser energy density, the optoacoustic transducer can work stable for long time. These encouraging results demonstrate that this work can provide significant guidance for the exploration and utilization of optoacoustic transducers.

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