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1.
Proc Natl Acad Sci U S A ; 121(13): e2319429121, 2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38513095

RESUMEN

Polyamines are a class of small polycationic alkylamines that play essential roles in both normal and cancer cell growth. Polyamine metabolism is frequently dysregulated and considered a therapeutic target in cancer. However, targeting polyamine metabolism as monotherapy often exhibits limited efficacy, and the underlying mechanisms are incompletely understood. Here we report that activation of polyamine catabolism promotes glutamine metabolism, leading to a targetable vulnerability in lung cancer. Genetic and pharmacological activation of spermidine/spermine N1-acetyltransferase 1 (SAT1), the rate-limiting enzyme of polyamine catabolism, enhances the conversion of glutamine to glutamate and subsequent glutathione (GSH) synthesis. This metabolic rewiring ameliorates oxidative stress to support lung cancer cell proliferation and survival. Simultaneous glutamine limitation and SAT1 activation result in ROS accumulation, growth inhibition, and cell death. Importantly, pharmacological inhibition of either one of glutamine transport, glutaminase, or GSH biosynthesis in combination with activation of polyamine catabolism synergistically suppresses lung cancer cell growth and xenograft tumor formation. Together, this study unveils a previously unappreciated functional interconnection between polyamine catabolism and glutamine metabolism and establishes cotargeting strategies as potential therapeutics in lung cancer.


Asunto(s)
Neoplasias Pulmonares , Humanos , Glutamina , Poliaminas/metabolismo , Pulmón/metabolismo , Muerte Celular , Acetiltransferasas/genética , Acetiltransferasas/metabolismo , Espermina/metabolismo
2.
Proc Natl Acad Sci U S A ; 121(14): e2315509121, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38547055

RESUMEN

Dysregulation of polyamine metabolism has been implicated in cancer initiation and progression; however, the mechanism of polyamine dysregulation in cancer is not fully understood. In this study, we investigated the role of MUC1, a mucin protein overexpressed in pancreatic cancer, in regulating polyamine metabolism. Utilizing pancreatic cancer patient data, we noted a positive correlation between MUC1 expression and the expression of key polyamine metabolism pathway genes. Functional studies revealed that knockdown of spermidine/spermine N1-acetyltransferase 1 (SAT1), a key enzyme involved in polyamine catabolism, attenuated the oncogenic functions of MUC1, including cell survival and proliferation. We further identified a regulatory axis whereby MUC1 stabilized hypoxia-inducible factor (HIF-1α), leading to increased SAT1 expression, which in turn induced carbon flux into the tricarboxylic acid cycle. MUC1-mediated stabilization of HIF-1α enhanced the promoter occupancy of the latter on SAT1 promoter and corresponding transcriptional activation of SAT1, which could be abrogated by pharmacological inhibition of HIF-1α or CRISPR/Cas9-mediated knockout of HIF1A. MUC1 knockdown caused a significant reduction in the levels of SAT1-generated metabolites, N1-acetylspermidine and N8-acetylspermidine. Given the known role of MUC1 in therapy resistance, we also investigated whether inhibiting SAT1 would enhance the efficacy of FOLFIRINOX chemotherapy. By utilizing organoid and orthotopic pancreatic cancer mouse models, we observed that targeting SAT1 with pentamidine improved the efficacy of FOLFIRINOX, suggesting that the combination may represent a promising therapeutic strategy against pancreatic cancer. This study provides insights into the interplay between MUC1 and polyamine metabolism, offering potential avenues for the development of treatments against pancreatic cancer.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Pancreáticas , Ratones , Animales , Humanos , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Poliaminas/metabolismo , Transducción de Señal , Acetiltransferasas/genética , Acetiltransferasas/metabolismo , Mucina-1
3.
Proc Natl Acad Sci U S A ; 120(16): e2219458120, 2023 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-37040398

RESUMEN

The control over the self-assembly of complex structures is a long-standing challenge of material science, especially at the colloidal scale, as the desired assembly pathway is often kinetically derailed by the formation of amorphous aggregates. Here, we investigate in detail the problem of the self-assembly of the three Archimedean shells with five contact points per vertex, i.e., the icosahedron, the snub cube, and the snub dodecahedron. We use patchy particles with five interaction sites (or patches) as model for the building blocks and recast the assembly problem as a Boolean satisfiability problem (SAT) for the patch-patch interactions. This allows us to find effective designs for all targets and to selectively suppress unwanted structures. By tuning the geometrical arrangement and the specific interactions of the patches, we demonstrate that lowering the symmetry of the building blocks reduces the number of competing structures, which in turn can considerably increase the yield of the target structure. These results cement SAT-assembly as an invaluable tool to solve inverse design problems.

4.
J Neurochem ; 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38690648

RESUMEN

Atypical sustained attention is a symptom in a number of neurological and psychological conditions. Investigations into its neural underpinnings are required for improved management and treatment. Rodents are useful in investigating the neurobiology underlying atypical sustained attention and several rodent tasks have been developed for use in touchscreen testing platforms that mimic methodology used in human clinical attention assessment. This systematic review was conducted to assess how translatable these rodent tasks are to equivalent clinical human tasks. Studies using the rodent Continuous Performance Task (rCPT), Sustained Attention Task (SAT), and 5-choice CPT (5C-CPT) were sought and screened. Included in the review were 138 studies, using the rCPT (n = 21), SAT (n = 90), and 5C-CPT (n = 27). Translatability between rodent and human studies was assessed based on (1) methodological similarity, (2) performance similarity, and (3) replication of results. The 5C-CPT was found to be the most translatable cross-species paradigm with good utility, while the rCPT and SAT require adaptation and further development to meet these translatability benchmarks. With greater replication and more consistent results, greater confidence in the translation of sustained attention results between species will be engendered.

5.
BMC Infect Dis ; 23(1): 220, 2023 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-37029345

RESUMEN

BACKGROUND: Children with Mycoplasma pneumoniae pneumonia (MPP) are prone to a missed diagnosis at the early stages of the disease, which greatly affects the prognosis of children. In this study, the application value of Mycoplasma pneumoniae (MP) antibody titres and RNA detection for diagnosing MP infection in children with community-acquired pneumonia (CAP) was evaluated. The present study aimed to seek appropriate detection methods and strategies for early rapid diagnosis in children with MPP. METHODS: A retrospective study was conducted on 563 paediatric patients aged 1 month to 15 years with CAP who were admitted to Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology between July 2021 and February 2022. In all patients, throat swabs were collected for MP-RNA detection (simultaneous amplification and testing, SAT), and paired serum samples were collected for MP total antibody detection (particle agglutination, PA). RESULTS: The classification as MPP or non-MPP was based on clinical diagnosis, serum MP antibody titre, and clinical or laboratory evidence of infection by other pathogen(s). Among the 563 patients with pneumonia, 187 patients were in the MPP group, and 376 patients were in the non-MPP group. The Kappa values between the particle agglutination test at different titres (1:80, 1:160) and MP-RNA detection were 0.612 and 0.660 (P<0.01), and the consistency of the three methods was acceptable. When the single screening method was used, MP-RNA had the highest sensitivity (93.05%), while PA (1:160) had the highest specificity (100%). PA (1:80), with an area under the curve (AUC) of 0.822, was better than PA (1:160), with an AUC of 0.783, and there was a significant difference. When the combined screening methods were used, the AUC of MP-RNA parallel PA (1:160) was significantly higher than that of titres (1:80) (z=-4.906, P < 0.01). Except for MP-80, the efficacy of the other three test methods in females was slightly better than that in males. Among the differences in age distribution, PA (1:80) was slightly less effective in the 13-72 months age group than at other ages, and MP-RNA parallel PA (1:160) was slightly better than the younger age group (≤ 36 m). In the older age group (> 36 m), PA (1:160) was just the opposite, while MP-RNA was slightly better than other age groups in the 13-72 months age group. CONCLUSIONS: For the diagnosis of MPP in children at the early of the disease, the antibody titre (1:160) parallel MP-RNA should be given preference, and then the disease should be further classified according to the antibody titre level and the age of the child. The combined application of the two detection methods could complement each other and strengthen the advantages, providing reliable laboratory evidence for the clinical diagnosis and timely treatment of MPP. When using the PA method alone to provide a reference standard to clarify MP infection, the differential diagnosis ability of 1:80 for MPP is better than 1:160, especially for children younger than 36 months.


Asunto(s)
Infecciones Comunitarias Adquiridas , Neumonía por Mycoplasma , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Pruebas de Aglutinación , Anticuerpos Antibacterianos , Infecciones Comunitarias Adquiridas/diagnóstico , Diagnóstico Precoz , Mycoplasma pneumoniae/genética , Neumonía por Mycoplasma/diagnóstico , Estudios Retrospectivos
6.
J Intensive Care Med ; 38(6): 529-533, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36648173

RESUMEN

INTRODUCTION: Many patients who pass a spontaneous awakening trial (SAT) and spontaneous breathing trial (SBT) do not undergo extubation that day. We aimed to identify predictors of extubation on the day of passing an SBT and to develop prediction models for extubation among mechanically ventilated patients. METHODS: In a cohort of mechanically ventilated patients who had passed an SBT in a single, academic medical intensive care unit (ICU) from 2018 to 2019, we developed a logistic regression model for identifying predictors of extubation. RESULTS: Of 745 patients in our study, 77% were extubated the day they passed a SBT. Independent predictors of extubation included higher Richmond Agitation Sedation Scale (RASS) (-2 compared to -4: odds ratio (OR) 1.83, 95% confidence interval (CI) 1.56 to 2.14), receipt of sedation on the day prior (OR 2.12, 95% CI 1.63 to 2.74), absence of diagnosis of sepsis or septic shock (OR 0.77, 95% CI 0.59 to 1), absence of neurological illness (OR 0.59, 95% CI 0.37 to 0.96), indication for intubation of altered mental status, seizure, or agitation (OR 1.67, 95% CI 1.05 to 2.65), and absence of hemodynamic instability or cardiac arrest (OR 0.67, 95% CI 0.47 to 0.95). CONCLUSION AND RELEVANCE: Patients on mechanical ventilation were more likely to be extubated on the day they passed an SBT if they had higher RASS scores, received sedation the day prior, or did not have diagnosis of sepsis, neurological illness, or hemodynamic instability. Future research should attempt to identify and address modifiable risk factors for failure to extubate after passing an SBT.


Asunto(s)
Enfermedad Crítica , Sepsis , Adulto , Humanos , Extubación Traqueal , Enfermedad Crítica/terapia , Unidades de Cuidados Intensivos , Respiración Artificial , Desconexión del Ventilador
7.
Qual Life Res ; 32(4): 1107-1117, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36515757

RESUMEN

PURPOSE: We aimed to examine different effects of the current capability of and changes in self-management strategies on improving health behavior and psychological health (satisfaction of life, depression, and anxiety) after 6 months in cancer patients. METHODS: A prospective cohort study was conducted, including 540 cancer patients. We measured cancer patients' self-management strategies' capability with Smart Management Strategies for Health (SMASH) Assessment Tool (SAT) baseline scores and changes with SMASH change scores based on a clinically meaningful 10% change of the scores. We conducted adjusted multivariate multiple logistic regression analyses using the stepwise selection method between SMASH baseline and health behavior, satisfaction with life (SWL), depression, and anxiety and between SMASH changes and health behavior, SWL, depression, and anxiety. RESULTS: 256 cancer patients completed both the first and second surveys. While various SMASH capabilities positively affected each health behavior, SWL, depression, and anxiety, the positive-reframing strategy at baseline only affected all health behavior, SWL, and depression. However, based on SMASH changes, using the positive-reframing strategy a lot for 6 months adversely affected some physical health behaviors' practice (balanced diet and stop smoking and drinking). Changes in the life value pursuing strategy only positively affected HB (proactive living) and anxiety. CONCLUSION: SMASH baseline and change scores were generally associated with practicing cancer patients' health behaviors, lower depression, and anxiety. However, it is necessary to consider that excessively using the positive-reframing strategy would interfere with practicing a balanced diet and stopping smoking and drinking behaviors.


Asunto(s)
Neoplasias , Automanejo , Humanos , Estudios Prospectivos , Calidad de Vida/psicología , Depresión/terapia , Depresión/psicología , Neoplasias/terapia , Neoplasias/psicología , Conductas Relacionadas con la Salud , Ansiedad/terapia , Ansiedad/psicología , Encuestas y Cuestionarios
8.
Environ Toxicol ; 38(11): 2574-2584, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37598415

RESUMEN

Excess iodine will trigger the occurrence of autoimmune thyroiditis (AIT), and programmed death-1 (PD-1)/programmed death ligand (PD-L) will also contribute to the development of AIT. The purpose of this study was to explore the role that negative regulatory signals mediated by PD-1/PD-L play in the development of spontaneous autoimmune thyroiditis (SAT) in NOD.H-2h4 mice when they are exposed to iodine. Programmed death ligand 1 (PD-L1) antibody was administered intraperitoneally to NOD.H-2h4 mice. The relevant indicators were determined by flow cytometry, real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, immunohistochemistry, pathological hematoxylin and eosin staining, and arsenic-cerium catalytic spectrophotometry. Results showed that the level of urinary iodine, the level of thyroid lymphocyte infiltration, the level of thyroglobulin antibodies (TgAb) and interferon (IFN-γ)/tumor necrosis factor (TNF-α)/interleukin (IL-2)/IL-17, and the relative expression of PD-1/PD-L1/programmed death-2 (PD-L2) increased with the intervention of excess iodine. After the intervention of the PD-L1 antibody, the expression of PD-1/PD-L1/PD-L2 in different degrees was inhibited, but the level of thyroid lymphocyte infiltration and serum TgAb/IFN-γ/TNF-α/ IL-2/IL-17 did not decrease. Collectively, although PD-1/PD-L participates in the occurrence of SAT and induces inflammation, administration of the PD-L1 antibody does not effectively improve the pathological process of SAT. More research is needed to determine whether PD-1/PD-L intervention can treat autoimmune thyroid disease.

9.
Int J Mol Sci ; 24(17)2023 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-37686231

RESUMEN

Promising approaches to the treatment of obesity include increasing energy expenditure and slowing down fibrogenesis of adipose tissue. The neurotransmitter reuptake inhibitor sibutramine affects appetite and activates lipolysis in a catecholaminergic way. MicroRNAs (miRs) are considered as biomarkers of molecular genetic mechanisms underlying various processes. The profile of a number of miRs is altered in obesity, both in the circulation and in adipose tissue. The aim of this study was to assess the expression levels of miRs (hsa-miR-378a-3p, hsa-miR-142-3p) by real-time polymerase chain reaction in subcutaneous adipose tissue (SAT) and in plasma in patients with different degrees and duration of obesity and during sibutramine therapy. This study included 51 obese patients and 10 healthy subjects with normal weight who formed a control group. The study found that, before treatment, obese patients had no significant difference in the expression level of miR-378 in SAT and plasma compared to the control group, while the expression of miR-142 was significantly decreased in SAT and increased in plasma. A significant elevation in miR-378 expression level was noted in patients with first-degree obesity and duration of less than 10 years, and the decline in miR-142 increased with the duration of obesity. These data indicate a maximal increase in the expression of the adipogenesis inducer miR-378 in the early stages of obesity, a progressive decrease in the expression of the fibrogenesis inhibitor miR-142 in SAT with growth of duration of obesity and the likely presence of antifibrogenic effects of sibutramine realized through miR-142 activation.


Asunto(s)
Ciclobutanos , MicroARNs , Humanos , MicroARNs/genética , Biomarcadores , Obesidad/genética
10.
Int J Mol Sci ; 24(14)2023 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-37511043

RESUMEN

The fragment of satellite III (f-SatIII) is located in pericentromeric heterochromatin of chromosome 1. Cell with an enlarged f-SatIII block does not respond to various stimuli and are highly stress-susceptible. The fraction of f-SatIII in the cells of schizophrenia patients changed during antipsychotic therapy. Therefore, antipsychotics might reduce the f-SatIII content in the cells. We studied the action of haloperidol, risperidone and olanzapine (3 h, 24 h, 96 h) on human skin fibroblast lines (n = 10). The f-SatIII contents in DNA were measured using nonradioactive quantitative hybridization. RNASATIII were quantified using RT-qPCR. The levels of DNA damage markers (8-oxodG, γ-H2AX) and proteins that regulate apoptosis and autophagy were determined by flow cytometry. The antipsychotics reduced the f-SatIII content in DNA and RNASATIII content in RNA from HSFs. After an exposure to the antipsychotics, the autophagy marker LC3 significantly increased, while the apoptosis markers decreased. The f-SatIII content in DNA positively correlated with RNASATIII content in RNA and with DNA oxidation marker 8-oxodG, while negatively correlated with LC3 content. The antipsychotics arrest the process of f-SatIII repeat augmentation in cultured skin fibroblasts via the transcription suppression and/or through upregulated elimination of cells with enlarged f-SatIII blocks with the help of autophagy.


Asunto(s)
Antipsicóticos , Humanos , Antipsicóticos/farmacología , Variaciones en el Número de Copia de ADN , 8-Hidroxi-2'-Desoxicoguanosina , ADN , ARN , Benzodiazepinas
11.
Przegl Epidemiol ; 77(2): 136-145, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37823628

RESUMEN

Introduction: Subacute thyroiditis (SAT), also known as de Quatrain's thyroiditis or granulomatous thyroiditis, is an inflammatory disease of the thyroid. Most of the time, it manifests in the thirties to fifties and is more common in women. SAT can have either viral or post-viral origin. Some viruses, like influenza, COVID-19, Epstein-Barr virus, cytomegalovirus, hepatitis, coxsackievirus 16, and mumps virus, have been linked to SAT development. The COVID-19 pandemic has affected people's lives all around the world and has changed our attitude toward the treatment of many diseases. It has also made us look deeper into the subject in a way that we would be able to treat this sort of disease with a newer insight. Objective: Regarding the importance of this issue, we decided to summarize our extensive searches from online databases, including PubMed, Google Scholar, Medline, Web of Science, and Scopus until February 2023, which we found effective in elucidating the association of subacute thyroiditis and viral diseases. Method: Different online databases were searched for narrative review articles, systemic review articles, and original articles, which were published until February 2023. Result: According to the included studies, we found that there is a correlation between SAT and several viruses such as Epstein-Barr virus, influenza virus, human immunodeficiency virus, cytomegalovirus, oral and cervical virus, hepatitis, dengue virus, and SARS-COV-2. The effect of each of the viral diseases mentioned in the SAT is given in the text. Conclusions: According to the results mentioned in the text, because SAT may be challenging for early diagnosis, due to the potential of classic symptoms as well as the interference of similar clinical symptoms between thyrotoxicosis and viral reactions, the correlation between SAT and viral diseases should be considered so that we can avoid misdiagnosis and lateness.


Asunto(s)
COVID-19 , Infecciones por Virus de Epstein-Barr , Gripe Humana , Tiroiditis Subaguda , Femenino , Humanos , Infecciones por Virus de Epstein-Barr/complicaciones , Herpesvirus Humano 4 , Pandemias , Polonia , SARS-CoV-2 , Tiroiditis Subaguda/complicaciones , Tiroiditis Subaguda/diagnóstico
12.
BMC Cancer ; 22(1): 215, 2022 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-35227235

RESUMEN

BACKGROUND: Low-grade glioma (LGG) is susceptible to ferroptosis, which is involved in TMZ resistance. Ferroptosis induction can enhance the sensitivity to TMZ and synergistically kill glioma cells. T cell-promoted tumor ferroptosis is a vital anti-tumor mechanism of immune checkpoint inhibitors. The SAT1 activation is closely related to ferroptosis upon ROS induction due to the upregulation of arachidonate 15-lipoxygenase (ALOX15) expression. METHODS: The expression of SAT1 in pan-cancer and corresponding normal tissue from the TCGA data portal was primarily explored. The landscape of SAT1 and immune cell infiltration and their corresponding gene marker sets in different tissues were further explored. Additionally, we evaluated the relationships between SAT1 and the clinicopathologic parameters of LGG, and the disease-specific survival (DSS), progression-free interval (PFI), and overall survival (OS) were also assessed using KM survival curves and multivariate analysis in LGG. Meanwhile, the Gene Set Enrichment Analysis (GSEA) was also implemented to determine the potential effect of the SAT1 gene in LGG. Furthermore, the predictive power of SAT1 was validated using an independent LGG cohort from the Chinese Glioma Genome Atlas (CGGA) data. RESULTS: In general, the expression of SAT1 is different between most tumors and their adjacent normal tissues. The results demonstrated that SAT1 expression is positively associated with TMB in LGG, BRCA, and THYM. The results displayed that the expression level of SAT1 is obviously correlated with the level of infiltrating macrophages and CD8 + T cells, and the levels of most immune gene sets were associated with the SAT1 expression in LGG. Interestingly, univariate and multivariate models significantly indicated that the OS and PFI of patients with LGG with high SAT1 levels were poorer than those with low SAT1 expression in the TCGA LGG cohort. GSEA showed that SAT1 was involved in immune regulation and multiple signaling pathways. Finally, our analysis demonstrated that SAT1 was closely associated with IDH mutation, 1p19q codeletion, chemoradiotherapy resistance and disease recurrence. CONCLUSIONS: Abundant expression of SAT1 was related to poor disease prognosis and abundant immune cell infiltration in LGG.


Asunto(s)
Acetiltransferasas/metabolismo , Neoplasias del Sistema Nervioso Central/genética , Ferroptosis/genética , Glioma/genética , Linfocitos Infiltrantes de Tumor/metabolismo , Biomarcadores de Tumor/genética , Bases de Datos Genéticas , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Análisis de Supervivencia
13.
Vet Res ; 53(1): 63, 2022 Aug 04.
Artículo en Inglés | MEDLINE | ID: mdl-35927724

RESUMEN

Foot-and-mouth disease (FMD) is one of the most important livestock diseases restricting international trade. While African buffalo (Syncerus caffer) act as the main wildlife reservoir, viral and immune response dynamics during FMD virus acute infection have not been described before in this species. We used experimental needle inoculation and contact infections with three Southern African Territories serotypes to assess clinical, virological and immunological dynamics for thirty days post infection. Clinical FMD in the needle inoculated buffalo was mild and characterised by pyrexia. Despite the absence of generalised vesicles, all contact animals were readily infected with their respective serotypes within the first two to nine days after being mixed with needle challenged buffalo. Irrespective of the route of infection or serotype, there were positive associations between the viral loads in blood and the induction of host innate pro-inflammatory cytokines and acute phase proteins. Viral loads in blood and tonsil swabs were tightly correlated during the acute phase of the infection, however, viraemia significantly declined after a peak at four days post-infection (dpi), which correlated with the presence of detectable neutralising antibodies. In contrast, infectious virus was isolated in the tonsil swabs until the last sampling point (30 dpi) in most animals. The pattern of virus detection in serum and tonsil swabs was similar for all three serotypes in the direct challenged and contact challenged animals. We have demonstrated for the first time that African buffalo are indeed systemically affected by FMD virus and clinical FMD in buffalo is characterized by a transient pyrexia. Despite the lack of FMD lesions, infection of African buffalo was characterised by high viral loads in blood and oropharynx, rapid and strong host innate and adaptive immune responses and high transmissibility.


Asunto(s)
Virus de la Fiebre Aftosa , Fiebre Aftosa , Animales , Anticuerpos Antivirales , Búfalos , Comercio , Fiebre/veterinaria , Virus de la Fiebre Aftosa/fisiología , Inmunidad , Internacionalidad
14.
Cell Biol Int ; 46(10): 1704-1713, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35819096

RESUMEN

As the main component of seminiferous tubules, Sertoli cells are in close contact with germ cells and generate niche signals, which exhibit pivotal functions in spermatogenesis and male fertility. However, the regulatory mechanisms of Sertoli cell-germline interactions (SGIs) in the testes of neonatal mice (NM) remain largely unclear. Previously, we identified spermidine/spermine N1-acetyl transferase 2 (SAT2) and stromal interaction molecule 1 (STIM1) to be potential regulators of testicular cord formation via comparative proteomics analysis. Here, we demonstrated a novel role of SAT2 for SGIs during testicular development in NM. Testicular explants lacking SAT2 affected the mislocation, but not the quantity, of Sertoli cells, which led to maintenance defects in spermatogonial stem cells (SSCs). Interestingly, SAT2 was essential for the migration of TM4 cells, a Sertoli cell line. Mechanistically, SAT2 was able to bind STIM1, repress its expression, and regulate homeostasis of a reactive oxygen species/wingless type (WNT)/ß-catenin pathway in NM testes. Collectively, our study identified that SAT2 was able to regulate SGIs via a STIM1-mediated WNT signaling pathway.


Asunto(s)
Acetiltransferasas , Células de Sertoli , Molécula de Interacción Estromal 1 , Vía de Señalización Wnt , Acetiltransferasas/metabolismo , Animales , Células Germinativas/metabolismo , Masculino , Ratones , Especies Reactivas de Oxígeno/metabolismo , Células de Sertoli/metabolismo , Espermatogénesis/fisiología , Molécula de Interacción Estromal 1/metabolismo , Testículo/metabolismo , beta Catenina/metabolismo
15.
BMC Vet Res ; 18(1): 349, 2022 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-36114497

RESUMEN

BACKGROUND: Foot-and-Mouth Disease Virus (FMDV) is a positive-sense RNA virus of the family of the picornaviridæ that is responsible for one of the livestock diseases with the highest economic impact, the Foot-and-Mouth Disease (FMD). FMD is endemic in Rwanda but there are gaps in knowing its seroprevalence and molecular epidemiology. This study reports the FMD seroprevalence and molecular characterization of FMDV in Eastern Rwanda. RESULTS: The overall seroprevalence of FMD in the study area is at 9.36% in cattle and 2.65% in goats. We detected FMDV using molecular diagnostic tools such as RT-PCR and RT-LAMP and the phylogenetic analysis of the obtained sequences revealed the presence of FMDV serotype SAT 2, lineage II. Sequencing of the oropharyngeal fluid samples collected from African buffaloes revealed the presence of Prevotela ruminicola, Spathidium amphoriforme, Moraxella bovoculi Onchocerca flexuosa, Eudiplodinium moggii, Metadinium medium and Verrucomicrobia bacterium among other pathogens but no FMDV was detected in African buffaloes. CONCLUSIONS: We recommend further studies to focus on sampling more African buffaloes since the number sampled was statistically insignificant to conclusively exclude the presence or absence of FMDV in Eastern Rwanda buffaloes. The use of RT-PCR alongside RT-LAMP demonstrates that the latter can be adopted in endemic areas such as Rwanda to fill in the gaps in terms of molecular diagnostics. The identification of lineage II of SAT 2 in Rwanda for the first time shows that the categorised FMDV pools as previously established are not static over time.


Asunto(s)
Bison , Virus de la Fiebre Aftosa , Fiebre Aftosa , Enfermedades de las Cabras , Animales , Anticuerpos Antivirales , Búfalos , Bovinos , Fiebre Aftosa/epidemiología , Enfermedades de las Cabras/diagnóstico , Enfermedades de las Cabras/epidemiología , Cabras , Parques Recreativos , Filogenia , Estudios Seroepidemiológicos
16.
J Clin Lab Anal ; 36(3): e24205, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35137464

RESUMEN

BACKGROUND: The laboratory test results and serum-specific antibodies of patients with acute brucellosis initial infection were followed up and analyzed. METHODS: 70 patients in Hohhot City, Inner Mongolia Autonomous Region, with acute brucellosis were followed up for 360 days. Serum samples were collected at 0, 15, 30, 60, 90, 180, and 360 days after diagnosis and analyzed by Rose Bengal plate test (RBPT), colloidal gold test paper (GICA), and test tube agglutination test (SAT). The serum-specific antibodies IgG and IgM were detected. RESULTS: RBPT results: False negative (-) gradually increased with the extension of the course of disease, with the largest change in 30-60 days after diagnosis, and the constituent ratio increased by 12.9%. GICA results: The false negative increased with the course of disease, and the constituent ratio of false negative was 20.0% after 180 days of diagnosis. SAT results: 1:100 positive showed a ladder like decrease with the increase in the course of disease, and the largest decrease was 90-180 days, with a decrease of 34.3% in the constituent ratio. 360 days after diagnosis, the constituent ratio of positive was only 14.3%. During the follow-up period, the IgG average value fluctuated and the average IgM value decreased. CONCLUSION: The false-negative results of RBPT, GICA, and SAT increased with the course of disease, and the false-negative rates were higher than 20% after half a year. IgM level is beneficial to the early diagnosis of brucellosis, while IgG level is helpful to the judgment of brucellosis stage.


Asunto(s)
Anticuerpos Antibacterianos , Brucelosis , Pruebas de Aglutinación/métodos , Brucelosis/diagnóstico , Estudios de Seguimiento , Humanos , Rosa Bengala
17.
BMC Med Inform Decis Mak ; 22(1): 133, 2022 05 16.
Artículo en Inglés | MEDLINE | ID: mdl-35578278

RESUMEN

BACKGROUND: One of the most prevalent complications of Partial Nephrectomy (PN) is Acute Kidney Injury (AKI), which could have a negative impact on subsequent renal function and occurs in up to 24.3% of patients undergoing PN. The aim of this study was to predict the occurrence of AKI following PN using preoperative parameters by applying machine learning algorithms. METHODS: We included all adult patients (n = 723) who underwent open PN in our department since 1995 and on whom we have data on the pre-operative renal function. We developed a random forest (RF) model with Boolean satisfaction-based pruned decision trees for binary classification (AKI or non-AKI). Hyper-parameter grid search was performed to optimize the model's performance. Fivefold cross-validation was applied to evaluate the model. We implemented a RF model with greedy feature selection to binary classify AKI and non-AKI cases based on pre-operative data. RESULTS: The best model obtained a 0.69 precision and 0.69 recall in classifying the AKI and non-AKI groups on average (k = 5). In addition, the model's probability to correctly classify a new prediction is 0.75. The proposed model is available as an online calculator. CONCLUSIONS: Our model predicts the occurrence of AKI following open PN with (75%) accuracy. We plan to externally validate this model and modify it to minimally-invasive PN.


Asunto(s)
Lesión Renal Aguda/etiología , Aprendizaje Automático/clasificación , Nefrectomía/efectos adversos , Complicaciones Posoperatorias/etiología , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/epidemiología , Adulto , Algoritmos , Árboles de Decisión , Humanos , Nefrectomía/métodos , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/epidemiología
18.
Sensors (Basel) ; 22(21)2022 Oct 24.
Artículo en Inglés | MEDLINE | ID: mdl-36365827

RESUMEN

This paper proposes an integrated panoramic sun sensor (IPSS) for the small spherical satellite Q-SAT that has been working in orbit since 2020. IPSS is essentially a set of temperature-compensated photoelectric cells distributed on the spherical surface of Q-SAT. Compared with traditional sun sensors, IPSS has full spherical coverage of 4π so that the sun vector from any direction can be inversed. The mechatronic design and mathematical model of the proposed IPSS are presented. In-depth error analyses in terms of albedo effect, sampling error, parameter deviation, etc. are carried out. IPSS can provide a sun vector inversion accuracy of 1.5∘ where albedo disturbance does not dominate. Simulation results show that the measurement of IPSS together with a COTS magnetometer can support the three-axis attitude determination of satellites in various orbits and can adapt to the seasonal variations of subpolar points. Ground experimental results and on-orbit data have also verified the feasibility and performance of IPSS. Although the panoramic sun sensor is designed for the small spherical Q-SAT, it can also be applied to other satellites with limited power budgets.


Asunto(s)
Luz Solar , Simulación por Computador
19.
Sensors (Basel) ; 22(9)2022 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-35591125

RESUMEN

Coherent detection provides the optimum performance for free space optical (FSO) communication systems. However, such detection systems are expensive and require digital phase noise compensation. In this paper, the transmission performance of long-haul FSO system for ground-to-satellite communication based on a Kramers-Kronig (KK) transceiver is evaluated. KK transceivers utilize inexpensive direct detection receivers and the signal phase is retrieved from the received current using the well-known KK relations. KK transceivers are not sensitive to the laser phase noise and, hence, inexpensive lasers with large linewidths can be used at the transmitter. The transmission performance of coherent and KK transceivers is compared in various scenarios such as satellite-to-ground, satellite-to-satellite, and ground-to-satellite for weak, moderate, and strong turbulence. The results show that the transmission performance of a system based on the KK transceiver is comparable to that based on a coherent transceiver, but at a significantly lower system cost and complexity. It is shown that in the absence of turbulence, the coherent receiver has a ~3 dB performance advantage over the KK receiver. However, in the presence of strong turbulence, this performance advantage becomes negligible.

20.
J Neurophysiol ; 126(2): 361-372, 2021 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-34191623

RESUMEN

Humans and other animals often need to balance the desire to gather sensory information (to make the best choice) with the urgency to act, facing a speed-accuracy tradeoff (SAT). Given the ubiquity of SAT across species, extensive research has been devoted to understanding the computational mechanisms allowing its regulation at different timescales, including from one context to another, and from one decision to another. However, animals must frequently change their SAT on even shorter timescales-that is, over the course of an ongoing decision-and little is known about the mechanisms that allow such rapid adaptations. The present study aimed at addressing this issue. Human subjects performed a decision task with changing evidence. In this task, subjects received rewards for correct answers but incurred penalties for mistakes. An increase or a decrease in penalty occurring halfway through the trial promoted rapid SAT shifts, favoring speeded decisions either in the early or in the late stage of the trial. Importantly, these shifts were associated with stage-specific adjustments in the accuracy criterion exploited for committing to a choice. Those subjects who decreased the most their accuracy criterion at a given decision stage exhibited the highest gain in speed, but also the highest cost in terms of performance accuracy at that time. Altogether, the current findings offer a unique extension of previous work, by suggesting that dynamic cha*nges in accuracy criterion allow the regulation of the SAT within the timescale of a single decision.NEW & NOTEWORTHY Extensive research has been devoted to understanding the mechanisms allowing the regulation of the speed-accuracy tradeoff (SAT) from one context to another and from one decision to another. Here, we show that humans can voluntarily change their SAT on even shorter timescales-that is, over the course of a decision. These rapid SAT shifts are associated with dynamic adjustments in the accuracy criterion exploited for committing to a choice.


Asunto(s)
Conducta de Elección/fisiología , Adulto , Femenino , Humanos , Masculino , Tiempo de Reacción , Recompensa
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