RESUMEN

The vast majority of data obtained from sequence analysis of influenza A viruses (IAVs) have revealed that nonstructural 1 (NS1) proteins from H1N1 swine, H3N8 equine, H3N2 avian and the correspondent subtypes from dogs have a conserved four C-terminal amino acid motif when independent cross-species transmission occurs between these species. To test the influence of the C-terminal amino acid motifs of NS1 protein on the replication and virulence of IAVs, we systematically generated 7 recombinants, which carried naturally truncated NS1 proteins, and their last four C-terminal residues were replaced with PEQK and SEQK (for H1N1), EPEV and KPEI (for H3N8) and ESEV and ESEI (for H3N2) IAVs. Another recombinant was generated by removing the C-terminal residues by reverse genetics. Remarkably, the ESEI and KPEI motifs circulating in canines largely contributed efficient replication in cultured cells and these had enhanced virulence. In contrast, the avian ESEV motif was only responsible for high pathogenicity in mice. We examined the effects of these motifs upon interferon (IFN) induction. The 7 mutant viruses replicated in vitro in an IFN-independent manner, and the canine SEQK motif was able to induced higher levels of IFN-ß in human cell lines. These findings shed further new light on the role of the four C-terminal residues in replication and virulence of IAVs and suggest that these motifs can modulate viral replication in a species-specific manner.

Asunto(s)

Secuencias de Aminoácidos , Subtipo H1N1 del Virus de la Influenza A , Infecciones por Orthomyxoviridae , Proteínas no Estructurales Virales , Replicación Viral , Proteínas no Estructurales Virales/genética , Proteínas no Estructurales Virales/metabolismo , Proteínas no Estructurales Virales/química , Animales , Perros , Virulencia , Ratones , Subtipo H1N1 del Virus de la Influenza A/genética , Subtipo H1N1 del Virus de la Influenza A/patogenicidad , Subtipo H1N1 del Virus de la Influenza A/fisiología , Infecciones por Orthomyxoviridae/virología , Humanos , Células de Riñón Canino Madin Darby , Ratones Endogámicos BALB C , Enfermedades de los Perros/virología , Subtipo H3N2 del Virus de la Influenza A/genética , Subtipo H3N2 del Virus de la Influenza A/patogenicidad , Subtipo H3N2 del Virus de la Influenza A/fisiología , Subtipo H3N8 del Virus de la Influenza A/genética , Subtipo H3N8 del Virus de la Influenza A/patogenicidad , Femenino

RESUMEN

BACKGROUND: The complex interplay between Sirtuin 1 (SIRT1) and FOXO3 in endometrial cancer (EC) remains understudied. This research aims to unravel the interactions of deacetylase SIRT1 and transcription factor FOXO3 in EC, focusing on their impact on mitophagy and hormone resistance. METHODS: High-throughput sequencing, cell experiments, and bioinformatics tools were employed to investigate the roles and interactions of SIRT1 and FOXO3 in EC. Co-immunoprecipitation (Co-IP) assay was used to assess the interaction between SIRT1 and FOXO3 in RL95-2 cells. Functional assays were used to assess cell viability, proliferation, migration, invasion, apoptosis, and the expression of related genes and proteins. A mouse model of EC was established to evaluate tumor growth and hormone resistance under different interventions. Immunohistochemistry and TUNEL assays were used to assess protein expression and apoptosis in tumor tissues. RESULTS: High-throughput transcriptome sequencing revealed a close association between SIRT1, FOXO3, and EC development. Co-IP showed a protein-protein interaction between SIRT1 and FOXO3. Overexpression of SIRT1 enhanced FOXO3 deacetylation and activity, promoting BNIP3 transcription and PINK1/Parkin-mediated mitophagy, which in turn promoted cell proliferation, migration, invasion, and inhibited apoptosis in vitro, as well as increased tumor growth and hormone resistance in vivo. These findings highlighted SIRT1 as an upstream regulator and potential therapeutic target in EC. CONCLUSION: This study reveals a novel molecular mechanism underlying the functional relevance of SIRT1 in regulating mitophagy and hormone resistance through the deacetylation of FOXO3 in EC, thereby providing valuable insights for new therapeutic strategies.

Asunto(s)

Neoplasias Endometriales , Proteína Forkhead Box O3 , Mitofagia , Sirtuina 1 , Femenino , Proteína Forkhead Box O3/metabolismo , Proteína Forkhead Box O3/genética , Humanos , Mitofagia/genética , Sirtuina 1/metabolismo , Sirtuina 1/genética , Animales , Neoplasias Endometriales/metabolismo , Neoplasias Endometriales/genética , Neoplasias Endometriales/patología , Línea Celular Tumoral , Ratones , Acetilación , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Apoptosis/genética , Movimiento Celular , Resistencia a Antineoplásicos/genética

RESUMEN

Advances in single-cell transcriptomics provide an unprecedented opportunity to explore complex biological processes. However, computational methods for analyzing single-cell transcriptomics still have room for improvement especially in dimension reduction, cell clustering, and cell-cell communication inference. Herein, we propose a versatile method, named DcjComm, for comprehensive analysis of single-cell transcriptomics. DcjComm detects functional modules to explore expression patterns and performs dimension reduction and clustering to discover cellular identities by the non-negative matrix factorization-based joint learning model. DcjComm then infers cell-cell communication by integrating ligand-receptor pairs, transcription factors, and target genes. DcjComm demonstrates superior performance compared to state-of-the-art methods.

Asunto(s)

Comunicación Celular , Análisis de la Célula Individual , Transcriptoma , Análisis de la Célula Individual/métodos , Análisis por Conglomerados , Perfilación de la Expresión Génica/métodos , Humanos , Biología Computacional/métodos

RESUMEN

The uptake, translocation, and accumulation of mefentrifluconazole (MFZ), an innovative chiral triazole fungicide, in plants at the enantiomeric level are still unclear. Herein, we investigated the patterns and mechanisms of enantiomeric uptake, bioaccumulation, and translocation through several experiments. Rac-MFZ shows the strongest uptake and bioaccumulation capacity in wheat compared with its enantiomers, while S-(+)-MFZ has the highest translocation potential. Molecular docking provided evidence of the stronger translocation ability of S-(+)-MFZ than R-(-)-MFZ. Split-root experiments showed that MFZ and its enantiomers could undergo long-distance transport within the wheat. Active transport or facilitated and simple diffusion may be involved in the wheat uptake of MFZ. The limited acropetal translocation capability of MFZ may be attributed to the dominant uptake pathway of apoplastic. The concentrations of Rac-MFZ in different subcellular fractions varied greatly. In summary, this study provides novel insights for further understanding the behaviors of MFZ and its enantiomers in plants.

Asunto(s)

Fungicidas Industriales , Triazoles , Triticum , Triticum/metabolismo , Triticum/química , Triazoles/química , Triazoles/metabolismo , Fungicidas Industriales/metabolismo , Fungicidas Industriales/química , Estereoisomerismo , Transporte Biológico , Simulación del Acoplamiento Molecular , Raíces de Plantas/metabolismo , Raíces de Plantas/química

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OBJECTIVE: To analyze the epidemic characteristics of common respiratory tract infection pathogens in children with respiratory tract infection, and provide scientific basis for the prevention and control of respiratory tract infection. METHODS: A retrospective collection of clinical data was conducted on 11,538 children with respiratory tract infections at Luoyang Maternal and Child Health Hospital from December 2022 to November 2023. The types of respiratory tract infections, including upper and lower respiratory tract infections, as well as five respiratory pathogens: influenza A virus (influenza A), influenza B virus (influenza B virus, adenovirus (ADV), respiratory syncytial virus (RSV), and Mycoplasma pneumoniae (MP) infections, were analyzed and compared for different genders, ages, temperatures, and air quality in different months; And the changes of five pathogens in children with respiratory tract infections of different disease severity. RESULTS: From December 2022 to November 2023, a total of 11,538 children with respiratory infections were included in the analysis, including 6436 males and 5102 females, with an age of 4.92 ± 2.03 years. The proportion of upper respiratory tract infections is as high as 72.17%, and lower respiratory tract infections account for 27.83%. Among them, 2387 were positive for Flu A antigen, with a positive rate of 20.69%, 51 cases were positive for Flu B antigen, and the positive rate was 0.4%, 1296 cases were positive for adv antigen, with a positive rate of 11.23%, 868 cases were positive for RSV antigen, with a positive rate of 7.52%, 2481 cases were positive for MP IgM antibody or MP antigen, and the positive rate was 21.50%. Flu B in male children The infection rate of ADV and MP was higher than that of female children (p < 0.05); Among children in different age groups, the older the age, the older the Flu A The higher the infection rate of MP (p < 0.05), the higher the positive rate of RSV in children with younger age (p < 0.05). The positive rate of ADV in children aged 3-6 years and > 6 years was higher than that in children aged 0-3 years (p < 0.05); Flu A and MP are popular throughout the year, and the positive rate peaks during the period of temperature rise and air quality decline from February to March, and during the period of temperature drop and air quality index rise from August to November, The positive rate of RSV peaked after the turning point of temperature rise from March to April. The infection rate was higher during the period of sharp decline in air quality from March to May and sharp decline in temperature in November, The positive rate of ADV was higher at the turning point of temperature rise from February to March, and then the infection rate decreased. During the period of sharp temperature drop from August to November, the positive rate increased sharply, and the peak of infection occurred; As the disease worsens, The positive rates of Flu A, Flu B, RSV, MP and combined infection with more than two pathogens were all increased (p < 0.05). CONCLUSION: After the new coronavirus epidemic in 2022, Flu A and MP have the highest infection rate of respiratory pathogens in children, showing a peak growth in general, with epidemic characteristics changing with environmental temperature, air quality and seasons. The main disease type is upper respiratory tract infection, MP and adv infections were mainly in male children, Flu A, MP and ADV infections are more common in older children, RSV infection was more common in younger children; Flu A, Flu B, RSV and MP infection and the co infection of more than two pathogens may more easily lead to the occurrence of severe pneumonia.

Asunto(s)

Virus de la Influenza B , Infecciones del Sistema Respiratorio , Humanos , Femenino , Masculino , Preescolar , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/virología , Estudios Retrospectivos , Niño , Lactante , Virus de la Influenza B/aislamiento & purificación , China/epidemiología , Infecciones por Virus Sincitial Respiratorio/epidemiología , Infecciones por Virus Sincitial Respiratorio/virología , Mycoplasma pneumoniae , Virus de la Influenza A/aislamiento & purificación , Virus Sincitial Respiratorio Humano/aislamiento & purificación , Virus Sincitiales Respiratorios/aislamiento & purificación , Gripe Humana/epidemiología , Gripe Humana/virología , Neumonía por Mycoplasma/epidemiología , Neumonía por Mycoplasma/microbiología , Estaciones del Año

RESUMEN

OBJECTIVE: Femoral neck fractures (FNF) are known to have significant morbidity and mortality rates. Multiple chronic conditions (MCC) are defined as the presence of two or more chronic diseases that greatly affect the quality of life in older adults. The aim of this study is to explore the impact of MCC and Charlson comorbidity index (CCI) on surgical outcomes in patients with FNF. METHODS: Patients with FNF who underwent joint replacement surgery were selected for this study. Patients who had two or more diseases simultaneously were divided into two groups: the MCC group and the non-MCC (NMCC) group. The CCI was calculated to assess the severity of patients' comorbidities in the MCC group. Baseline data, surgical details, and prognosis-related indicators were analyzed and compared between the two patient groups. Spearman correlation analysis was performed to assess the relationship between CCI and length of hospital stay, Harris score, skeletal muscle index (SMI), and age. Univariate and multivariate logistic regression analysis was conducted to identify the risk factors for mortality in FNF patients at 1 and 5 years after surgery. RESULTS: A total of 103 patients were included in the MCC group, while the NMCC group consisted of 40 patients. However, the patients in the MCC group were found to be older, had a higher incidence of sarcopenia, and lower SMI values (p < 0.001). Patients in the MCC group had longer hospitalization times, lower Harris scores, higher intensive care unit (ICU) admission rates, and higher complication rates (p = 0.045, p = 0.035, p = 0.019, p = 0.010). Spearman correlation analysis revealed that CCI was positively correlated with hospitalization and age (p < 0.001, p < 0.001), while it was negatively correlated with Harris score and SMI value (p < 0.001, p < 0.001). Univariate and multivariate logistic regression analysis demonstrated that MCC patients had higher 1-year and 5-year mortality rates. Hospitalization time was identified as a risk factor for death in FNF patients 1 year after joint replacement (p < 0.001), whereas CCI and age were identified as risk factors for death 5 years after surgery (p < 0.001, p < 0.001). Kaplan-Meier survival analysis results showed that the difference in death time between the two groups of patients with MCC and NMCC was statistically significant (p < 0.001). Cox proportional hazard model analysis showed that CCI, age and SMI were risk factors affecting patient death. CONCLUSION: The surgical prognosis of patients with MCC, CCI and FNF is related. The higher the CCI, the worse the patient's function and the higher the long-term risk of death.

Asunto(s)

Comorbilidad , Fracturas del Cuello Femoral , Humanos , Fracturas del Cuello Femoral/cirugía , Fracturas del Cuello Femoral/mortalidad , Femenino , Masculino , Anciano , Estudios Retrospectivos , Anciano de 80 o más Años , Pronóstico , Factores de Riesgo , Tiempo de Internación/estadística & datos numéricos , Resultado del Tratamiento , Persona de Mediana Edad

RESUMEN

The inference of cell-cell communication (CCC) is crucial for a better understanding of complex cellular dynamics and regulatory mechanisms in biological systems. However, accurately inferring spatial CCCs at single-cell resolution remains a significant challenge. To address this issue, we present a versatile method, called DeepTalk, to infer spatial CCC at single-cell resolution by integrating single-cell RNA sequencing (scRNA-seq) data and spatial transcriptomics (ST) data. DeepTalk utilizes graph attention network (GAT) to integrate scRNA-seq and ST data, which enables accurate cell-type identification for single-cell ST data and deconvolution for spot-based ST data. Then, DeepTalk can capture the connections among cells at multiple levels using subgraph-based GAT, and further achieve spatially resolved CCC inference at single-cell resolution. DeepTalk achieves excellent performance in discovering meaningful spatial CCCs on multiple cross-platform datasets, which demonstrates its superior ability to dissect cellular behavior within intricate biological processes.

Asunto(s)

Comunicación Celular , Análisis de la Célula Individual , Transcriptoma , Análisis de la Célula Individual/métodos , Humanos , Perfilación de la Expresión Génica/métodos , Análisis de Secuencia de ARN/métodos , Animales , Algoritmos , Biología Computacional/métodos

RESUMEN

OBJECTIVE: This study aimed to explore the psychiatric symptoms and associated risk and protective factors among religious adolescents after 2-month home confinement against coronavirus disease-2019 (COVID-19) in China. METHODS: 11,603 Chinese adolescents in grades 7-9 were recruited in this survey. An online survey was designed to collect the data. Participants were measured using the Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7 Scale. RESULTS: Religious adolescents showed significantly more severe depressive and anxiety symptoms compared to non-religious. 249 (2.2%) reported COVID-19 exposure. Logistic regression analysis revealed that religiosity was a risk factor for the symptoms of depression (p=0.001) and anxiety (p<0.001). Moreover, among those adolescents with religious beliefs, psychological resilience was protective in preventing depressive and anxiety symptoms. At the same time, emotional abuse, emotional neglect, and a poor parent-child relationship were risk factors. CONCLUSION: Our finding indicates that religious adolescents easily develop depressive and anxiety symptoms, compared to non-religious adolescents. Moreover, those with emotional abuse, emotional abuse, and poor parent-child relationships are more likely to suffer from mental distress and should pay more attention to cope with their mental health.

RESUMEN

Precise segmentation for skin cancer lesions at different stages is conducive to early detection and further treatment. Considering the huge cost of obtaining pixel-perfect annotations for this task, segmentation using less expensive image-level labels has become a research direction. Most image-level label weakly supervised segmentation uses class activation mapping (CAM) methods. A common consequence of this method is incomplete foreground segmentation, insufficient segmentation, or false negatives. At the same time, when performing weakly supervised segmentation of skin cancer lesions, ulcers, redness, and swelling may appear near the segmented areas of individual disease categories. This co-occurrence problem affects the model's accuracy in segmenting class-related tissue boundaries to a certain extent. The above two issues are determined by the loosely constrained nature of image-level labels that penalize the entire image space. Therefore, providing pixel-level constraints for weak supervision of image-level labels is the key to improving performance. To solve the above problems, this paper proposes a joint unsupervised constraint-assisted weakly supervised segmentation model (UCA-WSS). The weakly supervised part of the model adopts a dual-branch adversarial erasure mechanism to generate higher-quality CAM. The unsupervised part uses contrastive learning and clustering algorithms to generate foreground labels and fine boundary labels to assist segmentation and solve common co-occurrence problems in weakly supervised skin cancer lesion segmentation through unsupervised constraints. The model proposed in the article is evaluated comparatively with other related models on some public dermatology data sets. Experimental results show that our model performs better on the skin cancer segmentation task than other weakly supervised segmentation models, showing the potential of combining unsupervised constraint methods on weakly supervised segmentation.

Asunto(s)

Algoritmos , Semántica , Neoplasias Cutáneas , Humanos , Neoplasias Cutáneas/diagnóstico por imagen , Neoplasias Cutáneas/patología , Procesamiento de Imagen Asistido por Computador/métodos , Interpretación de Imagen Asistida por Computador/métodos , Aprendizaje Automático Supervisado , Bases de Datos Factuales , Piel/diagnóstico por imagen , Piel/patología , Aprendizaje Automático no Supervisado

RESUMEN

Camptothecin (CPT) is a monoterpenoid indole alkaloid with a wide spectrum of anticancer activity. However, its application is hindered by poor solubility, lack of targeting specificity, and severe side effects. Structural derivatization of CPT and the development of suitable drug delivery systems are potential strategies for addressing these issues. In this study, we discovered that the protein Cytochrome P450 Family 1 Subfamily A Member 1 (CYP1A1) from Homo sapiens catalyzes CPT to yield 9-hydroxycamptothecin (9-HCPT), which exhibits increased water solubility and cytotoxicity. We then created a RNA-protein complex based drug delivery system with enzyme and pH responsiveness and improved the targeting and stability of the nanomedicine through protein module assembly. The subcellular localization of nanoparticles can be visualized using fluorescent RNA probes. Our results not only identified the protein CYP1A1 responsible for the structural derivatization of CPT to synthesize 9-HCPT but also offered potential strategies for enhancing the utilization of silk-based drug delivery systems in tumor therapy.

Asunto(s)

Camptotecina , Citocromo P-450 CYP1A1 , Sistemas de Liberación de Medicamentos , Camptotecina/química , Camptotecina/farmacología , Camptotecina/análogos & derivados , Humanos , Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP1A1/genética , ARN/química , Nanopartículas/química , Solubilidad , Línea Celular Tumoral

RESUMEN

Introduction: Hepatitis E (HE), caused by the Hepatitis E virus (HEV), is a significant cause of acute viral hepatitis globally and a major public health concern, particularly in specific high-prevalence areas in China, which have diverse transmission routes and regional differences. Identifying the primary risk factors for HE transmission is essential to develop targeted interventions for vulnerable populations. Methods: This study employed a 1:1 matched case-control methodology, using a standardized questionnaire complemented by medical records for data validation. Results: Among the 442 HE cases and 428 healthy controls, the case group had a higher prevalence of fatigue (46.21%) and loss of appetite (43.84%) compared to the control group. Furthermore, liver function indicators were significantly higher in the case group, with an average alanine aminotransferase (ALT) level of 621.94 U/L and aspartate aminotransferase (AST) level of 411.53 U/L. Severe HE patients were predominantly male, with significantly increased ALT and AST levels reaching 1443.81 U/L and 862.31 U/L respectively, along with a higher incidence of fatigue (90%) and loss of appetite (75%). Multifactorial analysis indicated that frequent dining out (OR = 2.553, 95%CI:1.686-3.868), poor hygiene conditions (OR = 3.889, 95%CI:1.399-10.807), and comorbid chronic illnesses (OR = 2.275, 95%CI:1.616-3.202) were risk factors for HE infection; conversely, good hygiene practices were protective factors against HE infection (OR = 0.698, 95%CI:0.521-0.934). Conclusion: In conclusion, HE infection in Zhejiang Province is closely associated with dietary habits and environmental hygiene, and individuals with chronic diseases or co-infections are at increased risk. This highlights the need for targeted health education to reduce the incidence of HE among these populations.

Asunto(s)

Hepatitis E , Humanos , Masculino , China/epidemiología , Estudios de Casos y Controles , Factores de Riesgo , Hepatitis E/epidemiología , Persona de Mediana Edad , Femenino , Adulto , Prevalencia , Encuestas y Cuestionarios , Virus de la Hepatitis E , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre

RESUMEN

Luminescent materials typically emit their fluorescence or phosphorescence at a specific wavelength with different excitation energies via the so-called Kasha's rule. If fluorescence or phosphorescence emission via anti-Kasha's rule could be achieved, it will hold great promise for applications in many fields. In this work, we report the synthesis and characterization of new metal-organic halide materials with dual emission of efficient room-temperature phosphorescence and fluorescence, which obey anti-Kasha's rule. Here, three emitting metal-organic halides with formula [ZnX2(bidpe)] (X = Cl for 1, X = Br for 2, X = I for 3, bidpe = 4,4'-bis(imidazol-1-yl)diphenyl ether) were prepared and their photophysical properties were investigated. The complexes exhibit dual emission of fluorescence and phosphorescence via anti-Kasha's rule, and their RTP properties of resultant products are modulated by halide substitution synthesis. DFT calculations indicate that the singlet states exhibit a halide-ligand charge transfer (XLCT) character while the triplet states are dominated by the intraligand π-π* transitions. Furthermore, the multilevel information encryption and anticounterfeiting applications are developed by virtue of anti-Kasha's rule emission.

RESUMEN

Effector proteins secreted by bacteria that infect mammalian and plant cells often subdue eukaryotic host cell defenses by simultaneously affecting multiple targets. However, instances when a bacterial effector injected in the competing bacteria sabotage more than a single target have not been reported. Here, we demonstrate that the effector protein, LtaE, translocated by the type IV secretion system from the soil bacterium Lysobacter enzymogenes into the competing bacterium, Pseudomonas protegens, affects several targets, thus disabling the antibacterial defenses of the competitor. One LtaE target is the transcription factor, LuxR1, that regulates biosynthesis of the antimicrobial compound, orfamide A. Another target is the sigma factor, PvdS, required for biosynthesis of another antimicrobial compound, pyoverdine. Deletion of the genes involved in orfamide A and pyoverdine biosynthesis disabled the antibacterial activity of P. protegens, whereas expression of LtaE in P. protegens resulted in the near-complete loss of the antibacterial activity against L. enzymogenes. Mechanistically, LtaE inhibits the assembly of the RNA polymerase complexes with each of these proteins. The ability of LtaE to bind to LuxR1 and PvdS homologs from several Pseudomonas species suggests that it can sabotage defenses of various competitors present in the soil or on plant matter. Our study thus reveals that the multi-target effectors have evolved to subdue cell defenses not only in eukaryotic hosts but also in bacterial competitors.

Asunto(s)

Proteínas Bacterianas , Lysobacter , Pseudomonas , Sistemas de Secreción Tipo IV , Pseudomonas/genética , Pseudomonas/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Lysobacter/genética , Lysobacter/metabolismo , Sistemas de Secreción Tipo IV/genética , Sistemas de Secreción Tipo IV/metabolismo , Regulación Bacteriana de la Expresión Génica , Oligopéptidos/metabolismo , Oligopéptidos/genética , Transactivadores/genética , Transactivadores/metabolismo , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Factor sigma/genética , Factor sigma/metabolismo

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BACKGROUND: To explore the correlation between short-chain fatty acids (SCFAs) in the peri-implant sulcular fluid (PISF) and peri-implant diseases. METHODS: PISF samples were obtained from implants that have been placed for at least 5 years, and peri-implant clinical parameters were examined. Gas chromatography-mass spectrometry and high-performance liquid chromatography were used to detect SCFAs in PISF. The correlation between SCFAs and clinical parameters was analyzed by Spearman's correlation. SCFAs related to peri-implant disease were identified by logistic regression and ranked by random forest analysis. RESULTS: Eighty-six implants were divided into a peri-implant health group (PIH-group, 35 implants), peri-implant mucositis group (PIM-group, 25 implants), and peri-implantitis group (PI-group, 26 implants) according to clinical and radiographic examination results. The PIM-group had significantly lower formic acid detection rate than the other two groups (p < 0.001). The PIM-group had significantly higher levels of acetic, propionic, and isovaleric acids than the PIH-group (p < 0.05). The PI-group had significantly higher levels of propionic, butyric, isobutyric, valeric, and isovaleric acids than the PIH-group (p < 0.05). The PI-group had significantly higher levels of butyric, isobutyric, and isovaleric acids than the PIM-group (p < 0.05). SCFAs (apart from hexanoic and succinic acids) were significantly and positively correlated with clinical parameters (p < 0.05). SCFAs related to peri-implant disease were ranked as follows: butyric, isovaleric, isobutyric, propionic, acetic, formic, and lactic acids. CONCLUSIONS: Elevated specific SCFAs are correlated with peri-implant disease. Recognition of this correlation may help in early identification of peri-implant disease and guide further clinical interventions.

RESUMEN

BACKGROUND: There is increasing interest in utilizing AI-generated content for gadolinium-free contrast-enhanced breast MRI. PURPOSE: To develop a generative model for gadolinium-free contrast-enhanced breast MRI and evaluate the diagnostic utility of the generated scans. STUDY TYPE: Retrospective. POPULATION: Two hundred seventy-six women with 304 breast MRI examinations (49 ± 13 years, 243/61 for training/testing). FIELD STRENGTH/SEQUENCE: ZOOMit diffusion-weighted imaging (DWI), T1-weighted volumetric interpolated breath-hold examination (T1W VIBE), and axial T2 3D SPACE at 3.0 T. ASSESSMENT: A generative model was developed to generate contrast-enhanced scans using precontrast T1W VIBE and DWI images. The generated and real images were quantitatively compared using the structural similarity index (SSIM), mean absolute error (MAE), and Dice similarity coefficient. Three radiologists with 8, 5, and 5 years of experience independently rated the image quality and lesion visibility on AI-generated and real images within various subgroups using a five-point scale. Four breast radiologists, with 8, 8, 5, and 5 years of experience, independently and blindly interpreted four reading protocols: unenhanced MRI protocol alone and combined with AI-generated scans, abbreviated MRI protocol, and full-MRI protocol. STATISTICAL ANALYSIS: Results were assessed using t-tests and McNemar tests. Using pathology diagnosis as reference standard, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for each reading protocol. A P value <0.05 was considered significant. RESULTS: In the test set, the generated images showed similarity to the real images (SSIM: 0.935 ± 0.047 [SD], MAE: 0.015 ± 0.012 [SD], and Dice coefficient: 0.726 ± 0.177 [SD]). No significant difference in lesion visibility was observed between real and AI-generated scans of the mass, non-mass, and benign lesion subgroups. Adding AI-generated scans to the unenhanced MRI protocol slightly improved breast cancer detection (sensitivity: 92.86% vs. 85.71%, NPV: 76.92% vs. 70.00%); achieved non-inferior diagnostic utility compared to the AB-MRI protocol and full-protocol (sensitivity: 92.86%, 95.24%; NPV: 75.00%, 81.82%). DATA CONCLUSION: AI-generated gadolinium-free contrast-enhanced breast MRI has potential to improve the sensitivity of unenhanced MRI in detecting breast cancer. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 3.

RESUMEN

Periplaneta americana residue is a byproduct of using Periplaneta americana in pharmaceutical research and development for extracting active ingredients. Three hundred Three-yellow chickens were selected for the experiment and randomly divided into 6 groups (5 replications per group, 10 chickens per replicate): the control group (group A) was fed a basal ration, and the experimental groups (groups B, C, D, E, and F) were fed experimental diets in which P. americana residue replaced puffed soybean meal at proportions of 20, 40, 60, 80, and 100%, respectively, for a period of 42 d. The aim was to assess the impact of different levels of P. americana residue on the growth, survival, intestinal morphology, digestive enzyme activity, intestinal flora, and intestinal transcriptional responses of Three-yellow chickens. The results indicated that the increase in P. americana residue levels had a linear and quadratic impact on the average daily gain (ADG) and feed conversion ratio (FCR), respectively. The ADG was notably greater in the 40% group than in the 100% group, while the FCR was significantly lower in the 20% and 40% groups than in the 100% group (P < 0.05). Protease, lipase, and amylase activities exhibited a quadratic increase with increasing concentrations of P. americana residue (P < 0.05). Protease and lipase activities were notably greater in the 20% and 40% groups than in the 0% group (control group), amylase activity was significantly greater in the 40% group than in the 0% group (control group) (P < 0.05). Duodenal crypt depth (CD) decreased quadratically with increasing P. americana residue (P < 0.05). The duodenal villus height/crypt depth ratio (V/C) was significantly lower in the 100% group than in the 60% group (P < 0.05). The intestinal villus height (VH) increased quadratically with increasing levels of P. americana residue. The VH in the 60% group was significantly greater than that in the 0% (control group), 20, 80, and 100% groups (P < 0.05). The Chao and Ace indices demonstrated linear and quadratic increases with increasing levels of P. americana residue, while the Pd index showed a quadratic increase with increasing levels of P. americana residue (P < 0.05). The relative abundance profile of Lactobacillus exhibited a linear and quadratic decrease with increasing levels of P. americana residue, with the 100% group showing a significantly lower abundance than the 0% (control group) and 40% groups (P < 0.05). The transcriptome results showed that P. americana residue could enhance the digestive system by promoting vitamin, fat, carbohydrate digestion and absorption, cholesterol metabolism, etc. In conclusion, P. americana residue can replace puffed soybean meal without negatively affecting the growth performance of three-yellow chickens. The low and medium groups had positive effects on the growth performance, digestive enzyme activity, intestinal morphology, intestinal flora, and substance digestion and absorption of three-yellow chickens. The recommended replacement of P. americana residue for puffed soybean meal in the diets of three-yellow chickens ranged from 20% to 60%.

Asunto(s)

Alimentación Animal , Pollos , Dieta , Glycine max , Periplaneta , Animales , Pollos/crecimiento & desarrollo , Pollos/fisiología , Dieta/veterinaria , Alimentación Animal/análisis , Glycine max/química , Distribución Aleatoria , Fenómenos Fisiológicos Nutricionales de los Animales , Masculino , Microbioma Gastrointestinal/fisiología , Relación Dosis-Respuesta a Droga , Intestinos/anatomía & histología

RESUMEN

Persister cells are transiently tolerant to antibiotics and are associated with recalcitrant chronic infections due to recolonization of host cells after antibiotic removal. Brucella spp. are facultative pathogens that establish intracellular infection cycles in host cells which results in chronic persistent infections. Brucella abortus forms multi-drug persister cells which are promoted by the (p)ppGpp synthetase Rsh during rifampicin exposure. Here, we confirmed that Rsh promoted persister cells formation in B. abortus stationary phase treated with rifampicin and enrofloxacin. Deletion of the gene for Rsh decreased persister cells level in the presence of these drugs in different growth phases. However, persister cells formation by deletion strain varied in different growth phases in the presence of other antibiotics. Rsh also was involved in persister cells formation during rifampicin treatment under certain stress conditions, including acidic conditions, exposure to PBS, and heat stress. Moreover, Rsh impacted persister cell levels during rifampicin or enrofloxacin treatment in RAW264.7 macrophages. Certain typeIItoxin-antitoxin modules were upregulated under various stress conditions in B. abortus. We established that Rsh positively regulated the type II toxin-antitoxin mbcTA. Moreover, rifampicin-tolerant persister cells formation was elevated and ATP levels were decreased when mbcTA promoter was overexpressed in Rsh deletion background in stationary phase. Our results establish that (p)ppGpp synthetase Rsh plays a key role in B. abortus persistence and may serve as a potent novel target in combination with rifampicin in the development of new therapeutic approaches and prevention strategies to treat chronic infections of Brucella.

Asunto(s)

Proteínas de Fusión Oncogénica , Humanos , Proteínas de Fusión Oncogénica/genética , Masculino , Factores de Transcripción

RESUMEN

High-grade B-cell lymphoma (HGBCL), the subtype of non-Hodgkin lymphoma, to be relapsed or refractory in patients after initial therapy or salvage chemotherapy. Dual dysregulation of MYC and BCL2 is one of the important pathogenic mechanisms. Thus, combined targeting of MYC and BCL2 appears to be a promising strategy. Dihydroorotate dehydrogenase (DHODH) is the fourth rate-limiting enzyme for the de novo biosynthesis of pyrimidine. It has been shown to be a potential therapeutic target for multiple diseases. In this study, the DHODH inhibitor brequinar exhibited growth inhibition, cell cycle blockade, and apoptosis promotion in HGBCL cell lines with MYC and BCL2 rearrangements. The combination of brequinar and BCL2 inhibitors venetoclax had a synergistic inhibitory effect on the survival of DHL cells through different pathways. Venetoclax could upregulate MCL-1 and MYC expression, which has been reported as a resistance mechanism of BCL2 inhibitors. Brequinar downregulated MCL-1 and MYC, which could potentially overcome drug resistance to venetoclax in HGBCL cells. Furthermore, brequinar could downregulate a broad range of genes, including ribosome biosynthesis genes, which might contribute to its anti-tumor effects. In vivo studies demonstrated synergetic tumor growth inhibition in xenograft models with brequinar and venetoclax combination treatment. These results provide preliminary evidence for the rational combination of DHODH and BCL2 blockade in HGBCL with abnormal MYC and BCL2.

Asunto(s)

Compuestos Bicíclicos Heterocíclicos con Puentes , Dihidroorotato Deshidrogenasa , Sinergismo Farmacológico , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH , Proteínas Proto-Oncogénicas c-bcl-2 , Proteínas Proto-Oncogénicas c-myc , Sulfonamidas , Ensayos Antitumor por Modelo de Xenoinjerto , Humanos , Animales , Proteínas Proto-Oncogénicas c-bcl-2/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Ratones , Sulfonamidas/farmacología , Sulfonamidas/uso terapéutico , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Proteínas Proto-Oncogénicas c-myc/genética , Proteínas Proto-Oncogénicas c-myc/metabolismo , Proteínas Proto-Oncogénicas c-myc/antagonistas & inhibidores , Línea Celular Tumoral , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH/antagonistas & inhibidores , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH/genética , Apoptosis/efectos de los fármacos , Linfoma de Células B/tratamiento farmacológico , Linfoma de Células B/genética , Linfoma de Células B/patología , Linfoma de Células B/metabolismo , Reordenamiento Génico , Proliferación Celular/efectos de los fármacos , Compuestos de Bifenilo , Quinaldinas

RESUMEN

Histamine is a biogenic amine with various physiological functions. However, excessive consumption of histamine can lead to various symptoms, and pose a threat to human lives. A ratiometric fluorescent test strip for visual detection of histamine was developed based on CB-Ni2+@CDs probes. As the concentration of histamine increases, the test strips exhibit a transition in fluorescence signal from yellow-green to blue. The RGB values were extracted from the images, and used for quantitative analysis of histamine. The method had a linear range of 0-1.0 mM, with a detection limit of 0.086 mM. The test strips were employed for the detection of histamine, and the recovery rate was found to be in the range of 88.3% to 104.69%, indicating a high level of accuracy. The uniqueness of the test strips lies in their ability to be produced simply by mixing CB, Ni2+ on a suitable polyvinyl alcohol/wood cellulose fiber substrate.