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Given the serious neurological complications and deaths associated with enterovirus 71 (EV71) infection, there is an urgent need to develop effective antivirals against this viral infection. In this study, we demonstrated that two Cathelicidin-derived peptides, LL-18 and FF-18 were more potent against EV71 infection than the parent peptide LL-37, which is the mature and processed form of Cathelicidin. These peptides could directly bind to the EV71 virus particles, but not to coxsackievirus, indicative of their high specificity. The binding of peptides with the virus surface occupied the viral canyon region in a way that could block virus-receptor interactions and inhibit viral uncoating. In addition, these peptide analogues could also relieve the deleterious effect of EV71 infection in vivo. Therefore, Cathelicidin-derived peptides might be excellent candidates for further development of antivirals to treat EV71 infection.
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Enterovirus Humano A , Infecciones por Enterovirus , Enterovirus , Humanos , Catelicidinas/farmacología , Internalización del Virus , Antivirales/metabolismoRESUMEN
Plants have evolved sophisticated mechanisms to coordinate their growth and stress responses via integrating various phytohormone signaling pathways. However, the precise molecular mechanisms orchestrating integration of the phytohormone signaling pathways remain largely obscure. In this study, we found that the rice (Oryza sativa) short internodes1 (shi1) mutant exhibits typical auxin-deficient root development and gravitropic response, brassinosteroid (BR)-deficient plant architecture and grain size as well as enhanced abscisic acid (ABA)-mediated drought tolerance. Additionally, we found that the shi1 mutant is also hyposensitive to auxin and BR treatment but hypersensitive to ABA. Further, we showed that OsSHI1 promotes the biosynthesis of auxin and BR by activating the expression of OsYUCCAs and D11, meanwhile dampens ABA signaling by inducing the expression of OsNAC2, which encodes a repressor of ABA signaling. Furthermore, we demonstrated that 3 classes of transcription factors, AUXIN RESPONSE FACTOR 19 (OsARF19), LEAF AND TILLER ANGLE INCREASED CONTROLLER (LIC), and OsZIP26 and OsZIP86, directly bind to the promoter of OsSHI1 and regulate its expression in response to auxin, BR, and ABA, respectively. Collectively, our results unravel an OsSHI1-centered transcriptional regulatory hub that orchestrates the integration and self-feedback regulation of multiple phytohormone signaling pathways to coordinate plant growth and stress adaptation.
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Oryza , Reguladores del Crecimiento de las Plantas , Reguladores del Crecimiento de las Plantas/metabolismo , Oryza/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Ácido Abscísico/metabolismo , Ácidos Indolacéticos/metabolismo , Brasinoesteroides/metabolismo , Hormonas , Crecimiento y Desarrollo , Regulación de la Expresión Génica de las PlantasRESUMEN
Enterovirus 71 (EV71) is one of the major pathogens causing hand, foot, and mouth disease in children under 5 years old, which can result in severe neurological complications and even death. Due to limited treatments for EV71 infection, the identification of novel host factors and elucidation of mechanisms involved will help to counter this viral infection. N-terminal acetyltransferase 6 (NAT6) was identified as an essential host factor for EV71 infection with genome-wide CRISPR/Cas9 screening. NAT6 facilitates EV71 viral replication depending on its acetyltransferase activity but has little effect on viral release. In addition, NAT6 is also required for Echovirus 7 and coxsackievirus B5 infection, suggesting it might be a pan-enterovirus host factor. We further demonstrated that NAT6 is required for Golgi integrity and viral replication organelle (RO) biogenesis. NAT6 knockout significantly inhibited phosphatidylinositol 4-kinase IIIß (PI4KB) expression and PI4P production, both of which are key host factors for enterovirus infection and RO biogenesis. Further mechanism studies confirmed that NAT6 formed a complex with its substrate actin and one of the PI4KB recruiters-acyl-coenzyme A binding domain containing 3 (ACBD3). Through modulating actin dynamics, NAT6 maintained the integrity of the Golgi and the stability of ACBD3, thereby enhancing EV71 infection. Collectively, these results uncovered a novel mechanism of N-acetyltransferase supporting EV71 infection.IMPORTANCEEnterovirus 71 (EV71) is an important pathogen for children under the age of five, and currently, no effective treatment is available. Elucidating the mechanism of novel host factors supporting viral infection will reveal potential antiviral targets and aid antiviral development. Here, we demonstrated that a novel N-acetyltransferase, NAT6, is an essential host factor for EV71 replication. NAT6 could promote viral replication organelle (RO) formation to enhance viral replication. The formation of enterovirus ROs requires numerous host factors, including acyl-coenzyme A binding domain containing 3 (ACBD3) and phosphatidylinositol 4-kinase IIIß (PI4KB). NAT6 could stabilize the PI4KB recruiter, ACBD3, by inhibiting the autophagy degradation pathway. This study provides a fresh insight into the relationship between N-acetyltransferase and viral infection.
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Enterovirus Humano A , Infecciones por Enterovirus , Acetiltransferasas N-Terminal , Fosfotransferasas (Aceptor de Grupo Alcohol) , Niño , Preescolar , Humanos , 1-Fosfatidilinositol 4-Quinasa/metabolismo , Actinas/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Antivirales , Coenzima A/metabolismo , Infecciones por Coxsackievirus , Enterovirus Humano A/fisiología , Infecciones por Enterovirus/metabolismo , Infecciones por Enterovirus/virología , Proteínas de la Membrana/metabolismo , Acetiltransferasas N-Terminal/metabolismo , Biogénesis de Organelos , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo , Replicación Viral/fisiologíaRESUMEN
Human recombinant ACE2 (hrACE2) has been highly anticipated as a successful COVID-19 treatment; however, its potential to cause cardiac side effects has given rise to many concerns. Here, we developed a cardiotoxicity-eliminated hrACE2 variant, which had four mutation sites within hrACE2 (H345L, H374L, H378L, H505L) and was named as hrACE2-4mu. hrACE2-4mu has a consistent binding affinity with the variant SARS-CoV-2 spike proteins (SPs) and an efficient ability to block SP-induced SARS-CoV-2 entry into cells. In golden hamsters, injection of purified wild-type (WT) hrACE2 rescues the early stages of pneumonia caused by the SPs of the WT, delta, and omicron variants with reduced inflammatory cell infiltration. However, long-term injection of WT hrACE2 induces undesired cardiac fibrosis, as demonstrated by upregulated fibronectin and collagen expression. Our newly developed hrACE2-4mu showed similar protective abilities against a series of coronavirus cell invasions as WT hrACE2, meanwhile it did not cause apparent cardiac side effects. Thus, we generated a cardiotoxicity-eliminated variant of hrACE2 as a pan-inhibitor against coronavirus cell invasion, providing a potential novel strategy for the treatment of COVID-19 and other coronaviruses.
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Enzima Convertidora de Angiotensina 2 , COVID-19 , Animales , Cricetinae , Humanos , Enzima Convertidora de Angiotensina 2/genética , Cardiotoxicidad/etiología , Tratamiento Farmacológico de COVID-19 , Corazón , MesocricetusRESUMEN
Nanosized ultrafine particles (UFPs) from natural and anthropogenic sources are widespread and pose serious health risks when inhaled by humans. However, tracing the inhaled UFPs in vivo is extremely difficult, and the distribution, translocation, and metabolism of UFPs remain unclear. Here, we report a label-free, machine learning-aided single-particle inductively coupled plasma mass spectrometry (spICP-MS) approach for tracing the exposure pathways of airborne magnetite nanoparticles (MNPs), including external emission sources, and distribution and translocation in vivo using a mouse model. Our results provide quantitative analysis of different metabolic pathways in mice exposed to MNPs, revealing that the spleen serves as the primary site for MNP metabolism (84.4%), followed by the liver (11.4%). The translocation of inhaled UFPs across different organs alters their particle size. This work provides novel insights into the in vivo fate of UFPs as well as a versatile and powerful platform for nanotoxicology and risk assessment.
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Hígado , Aprendizaje Automático , Nanopartículas de Magnetita , Espectrometría de Masas , Tamaño de la Partícula , Animales , Ratones , Nanopartículas de Magnetita/química , Espectrometría de Masas/métodos , Hígado/metabolismo , Bazo/metabolismo , Material Particulado/análisis , Material Particulado/química , Distribución TisularRESUMEN
Approximately 50% of colorectal cancer (CRC) patients would develop metastasis with poor prognosis, therefore, it is necessary to effectively predict metastasis in clinical treatment. In this study, we aimed to establish a machine-learning model for predicting metastasis in CRC patients by considering radiomics and transcriptomics simultaneously. Here, 1023 patients with CRC from three centers were collected and divided into five queues (Dazhou Central Hospital nâ =â 517, Nanchong Central Hospital nâ =â 120 and the Cancer Genome Atlas (TCGA) nâ =â 386). A total of 854 radiomics features were extracted from tumor lesions on CT images, and 217 differentially expressed genes were obtained from non-metastasis and metastasis tumor tissues using RNA sequencing. Based on radiotranscriptomic (RT) analysis, a novel RT model was developed and verified through genetic algorithms (GA). Interleukin (IL)-26, a biomarker in RT model, was verified for its biological function in CRC metastasis. Furthermore, 15 radiomics variables were screened through stepwise regression, which was highly correlated with the IL26 expression level. Finally, a radiomics model (RA) was established by combining GA and stepwise regression analysis with radiomics features. The RA model exhibited favorable discriminatory ability and accuracy for metastasis prediction in two independent verification cohorts. We designed multicenter, multi-scale cohorts to construct and verify novel combined radiomics and genomics models for predicting metastasis in CRC. Overall, RT model and RA model might help clinicians in directing personalized diagnosis and therapeutic regimen selection for patients with CRC.
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Neoplasias Colorrectales , Radiómica , Humanos , Pronóstico , Genómica , Expresión Génica , Neoplasias Colorrectales/diagnóstico por imagen , Neoplasias Colorrectales/genéticaRESUMEN
Cytochrome P450 3A4 (CYP3A4), a key enzyme, is pivotal in metabolizing approximately half of the drugs used clinically. The genetic polymorphism of the CYP3A4 gene significantly influences individual variations in drug metabolism, potentially leading to severe adverse drug reactions (ADRs). In this study, we conducted a genetic analysis on CYP3A4 gene in 1163 Chinese Han individuals to identify the genetic variations that might affect their drug metabolism capabilities. For this purpose, a multiplex polymerase chain reaction (PCR) amplicon sequencing technique was developed, enabling us to perform the genotyping of CYP3A4 gene efficiently and economically on a large scale. As a result, a total of 14 CYP3A4 allelic variants were identified, comprising six previously reported alleles and eight new nonsynonymous variants that were nominated as new allelic variants *39-*46 by the PharmVar Association. Further, functional assessments of these novel CYP3A4 variants were undertaken by coexpressing them with cytochromes P450 oxidoreductase (CYPOR) in Saccharomyces cerevisiae microsomes. Immunoblot analysis indicated that with the exception of CYP3A4.40 and CYP3A4.45, the protein expression levels of most new variants were similar to that of the wild-type CYP3A4.1 in yeast cells. To evaluate their catalytic activities, midazolam was used as a probe drug. The results showed that variant CYP3A4.45 had almost no catalytic activity, whereas the other variants exhibited significantly reduced drug metabolism abilities. This suggests that the majority of the CYP3A4 variants identified in the Chinese population possess markedly altered capacities for drug metabolism. SIGNIFICANCE STATEMENT: In this study, we established a multiplex polymerase chain reaction (PCR) amplicon sequencing method and detected the maximum number of new CYP3A4 variants in a single ethnic population. Additionally, we performed the functional characterizations of these eight novel CYP3A4 allele variants in vitro. This study not only contributes to the understanding of CYP3A4 genetic polymorphism in the Chinese Han population but also holds substantial reference value for their potential clinical applications in personalized medicine.
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Citocromo P-450 CYP3A , Polimorfismo Genético , Humanos , Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP3A/metabolismo , Alelos , Polimorfismo Genético/genética , Microsomas/metabolismo , ChinaRESUMEN
The accurate estimation of mutual information (MI) plays a vital role in understanding channel capacity and optimizing the performance of optical communications. While MI computations for the additive white Gaussian noise (AWGN) channel are well-established, they fall short when dealing with the challenges posed by nonlinear optical fiber channels due to an unknown channel model. For the first time, to our knowledge, this Letter introduces a mutual information neural estimator (MINE) for MI estimation in optical fiber communications. We propose an enhanced MINE (E-MINE), achieved by enlarging the training batch size to improve estimation accuracy and stability. Our findings reveal that the E-MINE achieves highly accurate estimations in the AWGN channel and maintains strong consistency with symbol-by-symbol MI estimations, comparable to Monte Carlo (MC) methods based on a Gaussian distribution in long-haul optical fiber channels. Furthermore, with multi-symbol estimation, the E-MINE yields a 0.16â bits/4D-symbol improvement in our experiments. We anticipate that our findings will drive further research in the field, opening new possibilities for enhancing communication systems design and performance using deep learning techniques.
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The mitotic quiescence of prospermatogonia is the event known to occur during genesis of the male germline and is tied to the development of the spermatogenic lineage. The regulatory mechanisms and the functional importance of this process have been demonstrated in mice; however, regulation of this process in human and domestic animal is still largely unknown. In this study, we employed single-cell RNA sequencing to identify transcriptional signatures of prospermatogonia and major somatic cell types in testes of goats at E85, E105, and E125. We identified both common and specific Gene Ontology categories, transcription factor regulatory networks, and cell-cell interactions in cell types from goat testis. We also analyzed the transcriptional dynamic changes in prospermatogonia, Sertoli cells, Leydig cells, and interstitial cells. Our datasets provide a useful resource for the study of domestic animal germline development.
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Cabras , Análisis de Expresión Génica de una Sola Célula , Masculino , Animales , Humanos , Ratones , Cabras/genética , Testículo/metabolismo , Espermatogénesis/genética , Células de Sertoli/metabolismo , Células Germinativas , Análisis de la Célula Individual , TranscriptomaRESUMEN
The anti-PD-1 antibodies have been reported to show a striking effect in relapsed and refractory(R/R) classical Hodgkin lymphoma (cHL), however, there is still limited real-world data assessing the role of anti-PD-1 antibody monotherapy in early-stage cHL. In this retrospective analysis, we reported the effectiveness and safety of tislelizumab monotherapy in the first-line therapy of early-stage cHL. Twenty-three consecutive patients (10 males and 13 females) with previously untreated stage I A-II B cHL were included. At interim evaluation after 2 doses of tislelizumab monotherapy, 11 of 23 patients (47.8%) achieved complete response (CR). At the end of tislelizumab monotherapy (EOTM), objective response was observed in 22 of 23 patients (95.7%), with CR in 16 patients (69.6%). Among six patients with PR-EOTM, two patients underwent 4 cycles of ABVD chemotherapy and one patient underwent 4 cycles of tislelizumab plus AVD. One patient who developed progressive disease (PD) after 4 doses of tislelizumab subsequently underwent 4 cycles of ABVD chemotherapy. Except for four patients with CR-EOTM, consolidative radiotherapy was given to 19 patients. All patients obtained CR at the end of all treatments. With a median follow-up time of 21.3 months (range, 6.9-32.7 months), the estimated 2-year PFS rate and 2-year OS rate were 95.65% and 100%, respectively. Except for grade 3 lymphocyte count decreased, no other grade 3/4 TRAE was observed. In addition, no serious AE was reported. Our preliminary data observed that tislelizumab monotherapy was safe and highly effective in previously untreated early-stage cHL.
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Anticuerpos Monoclonales Humanizados , Enfermedad de Hodgkin , Masculino , Femenino , Humanos , Enfermedad de Hodgkin/terapia , Estudios Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica , Bleomicina/uso terapéutico , Vinblastina , Dacarbazina , DoxorrubicinaRESUMEN
INTRODUCTION: Lymphoma tissue biopsies cannot fully capture genetic features due to accessibility and heterogeneity. We aimed to assess the applicability of circulating tumor DNA (ctDNA) for genomic profiling and disease surveillance in classic Hodgkin lymphoma (cHL), primary mediastinal large B-cell lymphoma (PMBCL), and diffuse large B-cell lymphoma (DLBCL). METHODS: Tumor tissue and/or liquid biopsies of 49 cHLs, 32 PMBCLs, and 74 DLBCLs were subject to next-generation sequencing targeting 475 genes. The concordance of genetic aberrations in ctDNA and paired tissues was investigated, followed by elevating ctDNA-based mutational landscapes and the correlation between ctDNA dynamics and radiological response/progression. RESULTS: ctDNA exhibited high concordance with tissue samples in cHL (78%), PMBCL (84%), and DLBCL (78%). In cHL, more unique mutations were detected in ctDNA than in tissue biopsies (P < 0.01), with higher variant allele frequencies (P < 0.01). Distinct genomic features in cHL, PMBCL, and DLBCL, including STAT6, SOCS1, BTG2, and PIM1 alterations, could be captured by ctDNA alone. Prevalent PD-L1/PD-L2 amplifications were associated with more concomitant alterations in PMBCL (P < 0.01). Moreover, ctDNA fluctuation could reflect treatment responses and indicate relapse before imaging diagnosis. CONCLUSIONS: Lymphoma genomic profiling by ctDNA was concordant with that by tumor tissues. ctDNA might also be applied in lymphoma surveillance.
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OBJECTIVE: To investigate the occurrence of depressive disorders spanning the transition to retirement, and explore the relationship between retirement age and depressive disorders. METHODS: We utilized a national population-based health insurance database encompassing 2 million Taiwanese individuals from 2000 to 2019. The study focused on individuals aged 50 years and older who were employed at the baseline, and 84,224 individuals had records of retirement during the follow-up period. Depressive disorders were identified using codes from the International Classification of Diseases. To assess the trend in the incidence of depressive disorders 7-year period before and after retirement, an interrupted time series analysis was performed. Cox-proportional hazard models were employed to investigate the association between retirement age and the occurrence of depressive disorders following retirement. RESULTS: The incidence of depression peaks at the time of retirement and shows a significant decrease after retirement. Incidence of depressive disorders was 6.4 and 7.6 per 1000 person-years among individuals who retired between the ages of 60-64 and 65-69. Comparing the two groups, those who retired between 65 and 69 exhibits a higher risk of developing depressive disorders (hazard ratio = 1.10, 95% confidence interval = 1.02-1.18). This association is particularly pronounced among women and individuals residing in areas with low urbanization levels. CONCLUSION: Retirement marks a crucial life milestone accompanied by a peak in depressive disorders. It is important to address the higher risk of depression associated with late retirement among socially disadvantaged groups.
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Trastorno Depresivo , Jubilación , Humanos , Femenino , Persona de Mediana Edad , Anciano , Incidencia , Modelos de Riesgos Proporcionales , Depresión/epidemiología , Trastorno Depresivo/epidemiología , Estudios LongitudinalesRESUMEN
Cryptococcus neoformans is a widely distributed opportunistic pathogenic fungus. While Cryptococcus neoformans commonly infects immunocompromised individuals, it can also affect those who are immunocompetent. Transmission of Cryptococcus neoformans primarily occurs through the respiratory tract, leading to the development of meningitis. The mortality rate of Cryptococcal meningitis is high, and treatment options are limited. Cryptococcus neoformans infections pose a significant public health threat and currently lack targeted and effective response strategies. This study aimed to screen T lymphocyte(CTL, HTL) and B lymphocyte (LBL) epitopes derived from four Cryptococcus neoformans antigens and develop two multi-epitope vaccines by combining them with various adjuvants. Molecular docking results demonstrated that the vaccines bind stably to TLR4 and induce innate immunity. The credibility of the molecular docking results was validated through subsequent molecular dynamics simulations. Furthermore, the results of immune simulation analyses underscored the multi-epitope vaccine's capability to effectively induce robust humoral and cellular immune responses within the host organism. These two vaccines have demonstrated theoretical efficacy against Cryptococcus neoformans infection as indicated by computer analysis. Nevertheless, additional experimental validation is essential to substantiate the protective efficacy of the vaccines.
A multi-epitope Cryptococcus neoformans vaccine covering the most common A and D phenotypes was designed using bioinformatics methods.
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Many diseases in the human body are related to the overexpression of viscosity and sulfur dioxide. Therefore, it is essential to develop rapid and sensitive fluorescent probes to detect viscosity and sulfur dioxide. In the present work, we developed a dual-response fluorescent probe (ES) for efficient detection of viscosity and sulfur dioxide while targeting mitochondria well. The probe generates intramolecular charge transfer by pushing and pulling the electron-electron system, and the ICT effect is destroyed and the fluorescence quenched upon reaction with sulfite. The rotation of the molecule is inhibited in the high-viscosity system, producing a bright red light. In addition, the probe has good biocompatibility and can be used to detect sulfite in cells, zebrafish and mice, as well as upregulation of viscosity in LPS-induced inflammation models. We expect that the dual response fluorescent probe ES will be able to detect viscosity and sulfite efficiently, providing an effective means of detecting viscosity and sulfite-related diseases.
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Colorantes Fluorescentes , Inflamación , Mitocondrias , Sulfitos , Pez Cebra , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Colorantes Fluorescentes/toxicidad , Animales , Sulfitos/química , Sulfitos/análisis , Viscosidad , Mitocondrias/metabolismo , Mitocondrias/química , Ratones , Humanos , Inflamación/inducido químicamente , Dióxido de Azufre/análisis , Dióxido de Azufre/química , Lipopolisacáridos , Células RAW 264.7 , Imagen Óptica/métodosRESUMEN
The progress of organicsyntheticmethod can promote late-stage lead compound modification and novel active compound discovery. Molecular editing technology in the field of organic synthesis, including peripheral and skeletal editing, facilitates rapid access to molecular diversity of a lead compound. Peripheral editing of CH bond activation is gradually used in lead optimization to afford novel active scaffolds and chemical space exploitation. To develop oridonin derivatives with high anti-inflammatory potency, novel oridonin sulfamides had been designed and synthesized by a scaffoldhopping strategy based on a visible-light photocatalysis peripheral editing. All novel compounds revealed measurable inhibition of IL-1ß and low cytotoxicity in THP-1 cells. The docking study indicated that the best active compound ZM640 was accommodated in thebinding site of NLRP3 with two hydrogen bond interaction. These preliminary results confirm that α, ß-unsaturated carbonyl of oridonin is not essential for NLRP3 inhibitory effect. This new oridonin scaffold has its potential to be further developed as a promising class of NLRP3 inhibitors.
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Antineoplásicos , Diterpenos de Tipo Kaurano , Antineoplásicos/farmacología , Proteína con Dominio Pirina 3 de la Familia NLR , Diterpenos de Tipo Kaurano/farmacología , Diterpenos de Tipo Kaurano/química , Técnicas de Química SintéticaRESUMEN
Magnetic particles (MPs), with magnetite (Fe3O4) and maghemite (γ-Fe2O3) as the most abundant species, are ubiquitously present in the natural environment. MPs are among the most applied engineered particles and can be produced incidentally by various human activities. Identification of the sources of MPs is crucial for their risk assessment and regulation, which, however, is still an unsolved problem. Here, we report a novel approach, hierarchical classification-aided stable isotopic fingerprinting, to address this problem. We found that naturally occurring, incidental, and engineered MPs have distinct Fe and O isotopic fingerprints due to significant Fe/O isotope fractionation during their generation processes, which enables the establishment of an Fe-O isotopic library covering complex sources. Furthermore, we developed a three-level machine learning model that not only can distinguish the sources of MPs with a high precision (94.3%) but also can identify the multiple species (Fe3O4 or γ-Fe2O3) and synthetic routes of engineered MPs with a precision of 81.6%. This work represents the first reliable strategy for the precise source tracing of particles with multiple species and complex sources.
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Compuestos Férricos , Compuestos Férricos/químicaRESUMEN
Similarities between twins have been widely demonstrated, underscoring the remarkable influence of genetics across numerous traits. In this study, we explore the genetic underpinnings of the human brain by examining MRI data from the Queensland Twin Imaging study. Specifically, this study seeks to compare brain structure and function between twins and unrelated subjects, with an emphasis on describing the effects of genetic factors. To achieve these goals, we employed the source-based morphometry method to extract intrinsic components and elucidate recognizable patterns. Our results show that twins exhibit a higher degree of similarity in gray and white matter density compared with unrelated individuals. In addition, four distinct states of brain activity were identified using coactivation patterns analysis. Furthermore, twins demonstrated a greater degree of similarity in the temporal and spatial features of each state compared with unrelated subjects. Taken together, these results support the hypothesis that twins show greater similarity in both brain structure and dynamic functional brain activity. Further exploration of these methods may advance our understanding of the complex interplay between genes, environment, and brain networks.
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Imagen por Resonancia Magnética , Sustancia Blanca , Humanos , Imagen por Resonancia Magnética/métodos , Gemelos/genética , Encéfalo/diagnóstico por imagen , Encéfalo/fisiología , Cabeza , Gemelos Monocigóticos , Gemelos DicigóticosRESUMEN
BACKGROUND: Few cases describing patients with a right aortic arch (RAA) or double aortic arch (DAA) and esophageal cancer (EC) have been reported. METHODS: We analyzed RAA and DAA cases treated with esophagectomy in our center's database and reported in English-language studies until April 1, 2023. Our study assessed the malformation characteristics and surgical details of EC patients with RAA and DAA. RESULTS: We extracted data of 24 EC patients with RAAs and 10 EC patients with DAAs. In both groups, the patients were more likely to be Japanese and male, to have squamous cell carcinoma and to have tumors located in the upper thoracic esophagus or middle thoracic esophagus. Left thoracotomy was commonly applied for RAA patients. For DAA patients, the proportions of left-sided and right-sided approaches were similar. Esophagectomy under video-assisted thoracoscopic surgery (VATS) in RAA or DAA patients had been performed on a routine basis in recent years. There were two anastomotic leakages in each group. Specifically, Kommerell diverticulum rupture occurred in 1 RAA patient; gastric tube dilation occurred in 1 DAA patient; and recurrent laryngeal nerve (RLN) injury occurred in 2 RAA patients. The postoperative course was uneventful for most patients in both cohorts. CONCLUSIONS: Esophageal carcinoma is rarely seen in patients with an RAA or DAA. To adequately dissect superior mediastinal LNs, an auxiliary incision (such as sternotomy), the left door open method or a preceding cervical procedure should be used appropriately. Esophagectomy, whether via thoracotomy or thoracoscopic surgery, can be performed safely for both RAA and DAA.
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Carcinoma de Células Escamosas , Neoplasias Esofágicas , Anillo Vascular , Humanos , Masculino , Anillo Vascular/complicaciones , Anillo Vascular/cirugía , Anillo Vascular/patología , Aorta Torácica/cirugía , Aorta Torácica/anomalías , Aorta Torácica/patología , Neoplasias Esofágicas/cirugía , Neoplasias Esofágicas/patología , Cirugía Torácica Asistida por Video , Carcinoma de Células Escamosas/cirugía , Carcinoma de Células Escamosas/patología , Estudios RetrospectivosRESUMEN
BACKGROUND: The outer membrane vesicles (OMVs) produced by Gram-negative bacteria can modulate the immune system and have great potentials for bacterial vaccine development. RESULTS: A highly active Acinetobacter baumannii phage lysin, LysP53, can stimulate the production of OMVs after interacting with A. baumannii, Escherichia coli, and Salmonella. The OMVs prepared by the lysin (LOMVs) from A. baumannii showed better homogeneity, higher protein yield, lower endotoxin content, and lower cytotoxicity compared to the naturally produced OMVs (nOMVs). The LOMVs contain a significantly higher number of cytoplasmic and cytoplasmic membrane proteins but a smaller number of periplasmic and extracellular proteins compared to nOMVs. Intramuscular immunization with either LOMVs or nOMVs three times provided robust protection against A. baumannii infections in both pneumonia and bacteremia mouse models. Intranasal immunization offered good protection in the pneumonia model but weaker protection (20-40%) in the bacteremia model. However, with a single immunization, LOMVs demonstrated better protection than the nOMVs in the pneumonia mouse model. CONCLUSIONS: The novel lysin approach provides a superior choice compared to current methods for OMV production, especially for vaccine development.
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Infecciones por Acinetobacter , Acinetobacter baumannii , Bacteriófagos , Animales , Infecciones por Acinetobacter/prevención & control , Ratones , Femenino , Ratones Endogámicos BALB C , Vacunas Bacterianas/inmunología , Inmunización , Vesículas Extracelulares , Membrana Externa Bacteriana/metabolismo , Proteínas de la Membrana Bacteriana Externa/inmunología , Modelos Animales de Enfermedad , Humanos , Administración Intranasal , Proteínas ViralesRESUMEN
BACKGROUND: Despite the higher sensitivity of melanoma towards ferroptosis and photodynamic therapy (PDT), the lack of efficient ferroptosis inducers and the poor solubility of photosensitizers restrict their synergistic strategies. With unique advantages, carbon dots (CDs) are expected to serve as innovative building blocks for combination therapy of cancers. RESULTS: Herein, an ferroptosis/PDT integrated nanoplatform for melanoma therapy is constructed based on chlorin e6-modified Fe ions-doped carbon dots (Fe-CDs@Ce6). As a novel type of iron-carbon hybrid nanoparticles, the as-prepared Fe-CDs can selectively activate ferroptosis, prevent angiogenesis and inhibit the migration of mouse skin melanoma cells (B16), but have no toxicity to normal cells. The nano-conjugated structures facilitate not only the aqueous dispersibility of Ce6, but also the self-accumulation ability of Fe-CDs@Ce6 within melanoma area without requiring extra targets. Moreover, the therapeutic effects of Fe-CDs@Ce6 are synergistically enhanced due to the increased GSH depletion by PDT and the elevated singlet oxygen (1O2) production efficiency by Fe-CDs. When combined with laser irradiation, the tumor growth can be significantly suppressed by Fe-CDs@Ce6 through cyclic administration. The T2-weighted magnetic resonance imaging (MRI) capability of Fe-CDs@Ce6 also reveals their potentials for cancer diagnosis and navigation therapy. CONCLUSIONS: Our findings indicate the multifunctionality of Fe-CDs@Ce6 in effectively combining ferroptosis/PDT therapy, tumor targeting and MRI imaging, which enables Fe-CDs@Ce6 to become promising biocompatible nanoplatform for the treatment of melanoma.