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The phylum Nucleocytoviricota comprises a diverse group of double-stranded DNA viruses that display a wide range of gene repertoires. Although these gene repertoires determine the characteristics of individual viruses, the evolutionary processes that have shaped the gene repertoires of extant viruses since their common ancestor are poorly characterized. In this study, we aimed to address this gap in knowledge by using amalgamated likelihood estimation, a probabilistic tree reconciliation method that infers evolutionary scenarios by distinguishing origination, gene duplications, virus-to-virus horizontal gene transfer (vHGT), and gene losses. We analyzed over 4,700 gene families from 195 genomes spanning all known viral orders. The evolutionary reconstruction suggests a history of extensive gene gains and losses during the evolution of these viruses, notably with vHGT contributing to gene gains at a comparable level to duplications and originations. The vHGT frequently occurred between phylogenetically closely related viruses, as well as between distantly related viruses with an overlapping host range. We observed a pattern of massive gene duplications that followed vHGTs for gene families that was potentially related to host range control and virus-host arms race. These results suggest that vHGT represents a previously overlooked, yet important, evolutionary force that integrates the evolutionary paths of multiple viruses and affects shaping of Nucleocytoviricota virus gene repertoires.
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Transferencia de Gen Horizontal , Virus Gigantes , Virus Gigantes/genética , Evolución Molecular , Filogenia , Genoma Viral , Duplicación de GenRESUMEN
INTRODUCTION: Patients with hepatocellular carcinoma (HCC) and inferior vena cava tumor thrombus (IVCTT) have poor prognosis. Combination therapy involving the blockade of programmed cell death protein 1 (PD-1) and tyrosine kinase inhibitors is an efficient treatment strategy for advanced HCC. However, surgical treatment after a combination of systemic therapy and transarterial chemoembolization (TACE) for HCC with IVCTT has not been widely reported, and the efficacy and safety of this treatment have not been studied. METHODS: In the 21 cases reported herein, the patients were treated with TACE, lenvatinib, and PD-1 blockade. The treatment responses, progression-free survival (PFS), overall survival (OS), disease control rate, and toxicities were evaluated, and the related literature was reviewed. RESULTS: The overall response and disease control rates were 66.7% and 85.7%, respectively. The median PFS time was 16.0 months, with a 1-year PFS rate of 55.60%. The median OS was not reached, with a 1-year OS rate of 66.70%. Four patients underwent hepatectomy without serious complications and survived for 29.1, 24.7, 14.2, and 13.8 months. Three patients survived tumor-free, and 1 patient experienced intrahepatic recurrence. Pathological complete response and major pathological responses were observed in 1 and 3 patients, respectively. Treatment-related adverse events of any grade occurred in 8/9 patients (88.9%), and grade 3 treatment-related adverse events occurred in 1 patient. CONCLUSION: The combination of TACE, lenvatinib, and PD-1 is effective for HCC with IVCTT and has acceptable adverse effects.
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Purpose: The prognosis of patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) is extremely poor, and systemic therapy is currently the mainstream treatment. This study aimed to assess the efficacy and safety of lenvatinib combined with anti-PD-1 antibodies and transcatheter arterial chemoembolization (triple therapy) in patients with HCC and PVTT. Materials and Methods: This retrospective multicenter study included patients with HCC and PVTT who received triple therapy, were aged between 18 and 75 years, classified as Child Pugh class A or B, and had at least one measurable lesion. The overall survival (OS), progression-free survival (PFS), objective response rates, and disease control rates were analyzed to assess efficacy. Treatment-related adverse events were analyzed to assess safety profiles. Results: During a median follow-up of 11.23 months (range, 3.07-34.37 months), the median OS was greater than 24 months, and median PFS was 12.53 months. The two-year OS rate was 54.9%. The objective response rate and disease control rate were 69.8% (74/106) and 84.0% (89/106), respectively; 20.8% (22/106) of the patients experienced grade 3/4 treatment-related adverse events and no treatment-related deaths occurred. The conversion rate to liver resection was 31.1% (33/106), with manageable postoperative complications. The median OS was not reached in the surgery group, but was 19.08 months in the non-surgery group. The median PFS in the surgery and non-surgery groups were 20.50 and 9.00 months, respectively. Conclusion: Triple therapy showed promising survival benefits and high response rates in patients with HCC and PVTT, with manageable adverse effects.
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ASTRACT: One of the most common oral diseases affecting millions of people worldwide is periodontitis. Usually, proteins in body fluids are used as biomarkers of diseases. This study focused on hydrogen peroxide, lipopolysaccharide (LPS), and lactic acid as salivary non-protein biomarkers for oxidative stress conditions of periodontitis. Electrochemical analysis of artificial saliva was done using Gamry with increasing hydrogen peroxide, bLPS, and lactic acid concentrations. Electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) were conducted. From EIS data, change in capacitance and CV plot area were calculated for each test condition. Hydrogen peroxide groups had a decrease in CV area and an increase in percentage change in capacitance, lipopolysaccharide groups had a decrease in CV area and a decrease in percentage change in capacitance, and lactic acid groups had an increase of CV area and an increase in percentage change in capacitance with increasing concentrations. These data showed a unique combination of electrochemical properties for the three biomarkers. Scanning electron microscopy (SEM) with energy dispersive spectroscopy (EDS) employed to observe the change in the electrode surface and elemental composition data present on the sensor surface also showed a unique trend of elemental weight percentages. Machine learning models using hydrogen peroxide, LPS, and lactic acid electrochemical data were applied for the prediction of risk levels of periodontitis. The detection of hydrogen peroxide, LPS, and lactic acid by electrochemical biosensors indicates the potential to use these molecules as electrochemical biomarkers and use the data for ML-driven prediction tool for the periodontitis risk levels.
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Técnicas Biosensibles , Espectroscopía Dieléctrica , Peróxido de Hidrógeno , Ácido Láctico , Lipopolisacáridos , Estrés Oxidativo , Periodontitis , Saliva , Humanos , Saliva/química , Saliva/metabolismo , Periodontitis/metabolismo , Peróxido de Hidrógeno/análisis , Peróxido de Hidrógeno/metabolismo , Técnicas Biosensibles/métodos , Ácido Láctico/análisis , Ácido Láctico/metabolismo , Espectroscopía Dieléctrica/métodos , Biomarcadores/análisis , Biomarcadores/metabolismo , Aprendizaje AutomáticoRESUMEN
The incidence of thyroid carcinoma (TC) has exhibited a rapid increase in recent years. A proportion of TCs exhibit aggressive behavior. The present study aimed to investigate the potential role of hypoxiahypoxia inducible factor 1 subunit α (HIF1α)periostin axis in the progression of TC. The upregulation of periostin and HIF1α expression levels was detected in 95 clinical TC tissues as compared with normal thyroid tissues. Hypoxia promoted the viability and invasion of TC cells and this effect was inhibited by the downregulation of periostin. Hypoxia also induced the Warburg effect in TC and this effect was inhibited by the silencing of periostin. Further investigations revealed that hypoxia activated HIF1α, which in turn regulated the expression of periostin. Immunoprecipitation and dual luciferase reporter assays demonstrated that HIF1α upregulated the expression of periostin by binding to the promoter of periostin. On the whole, these findings suggest the existence of a hypoxiaHIF1αperiostin axis in TC and indicate the role of this axis in the progression of TC.
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Periostina , Neoplasias de la Tiroides , Humanos , Línea Celular Tumoral , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patología , Regulación hacia Arriba , Hipoxia , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Proliferación Celular/genéticaRESUMEN
Myocardial infarction is defined as a sudden decrease or interruption in blood flow to the coronary arteries, causing ischemic necrosis of the corresponding cardiomyocytes. It is unclear whether systemic macrovascular alterations are associated with retinal microvascular changes. This study utilized optical coherence tomography angiography (OCTA) to compare variations in conjunctival vascular density and fundus retinal vessel density between patients with myocardial infarction (MI) and healthy controls. This study recruited 16 patients (32 eyes) with MI and 16 healthy controls (32 eyes). The superficial retinal layer (SRL), deep retinal layer (DRL) and conjunctival capillary plexus in each eye were evaluated by OCTA. Parameters measured included the density of the temporal conjunctival capillary, retinal microvascular (MIR) and macrovascular (MAR) alterations and total MIR (TMI). The microvascular density of each retinal region was evaluated by the hemisphere segmentation (SR, SL, IL, and IR), annular partition (C1, C2, C3, C4, C5 and C6), and modified early treatment of diabetic retinopathy study (R, S, L, and I) methods. In the macular area, the superficial and deep retinal microvascular densities displayed notable variations. In the superficial layers, the superficial TMI, superficial MIR, and superficial MAR, as well as densities in the SL, IL, S, L, C1, C2, C5 and C6 regions, were significantly lower in MI patients (p < 0.05 each). In the deep layers, the deep MIR and deep TMI), as well as densities in the SL, IL, L, C1, C2 and C6 regions were significantly lower in MI patients (p < 0.05 each). In contrast, the conjunctival microvascular density was significantly higher in MI patients than in healthy controls (p < 0.001). The microvascular densities measured in the deep and superficial retinal layers and in the conjunctiva differ in MI patients and healthy controls. OCTA is effective in detecting changes in the ocular microcirculation.
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Infarto del Miocardio , Tomografía de Coherencia Óptica , Humanos , Angiografía con Fluoresceína/métodos , Tomografía de Coherencia Óptica/métodos , Vasos Retinianos/diagnóstico por imagen , Retina/diagnóstico por imagen , Infarto del Miocardio/diagnóstico por imagenRESUMEN
BACKGROUND: Combination treatment with transcatheter arterial chemoembolization (TACE), lenvatinib, and anti-programmed death-1 (anti-PD-1) antibodies (triple therapy) has a high rate of tumor response and converted resection for initially unresectable hepatocellular carcinoma (uHCC) patients. This study aimed to assess the outcomes of salvage surgery in uHCC patients after conversion therapy with triple therapy. METHODS: uHCC patients who met the criteria for hepatectomy after receiving triple therapy as first-line treatment were eligible for inclusion in this study. The overall survival (OS) and progression-free survival (PFS) rates in patients who received salvage surgery (SR group) and those who did not (non-SR group) were compared. RESULTS: Of the 144 patients assessed, 91 patients underwent salvage surgery and 53 did not. The OS rates in the SR group were significantly better than those in the non-SR group. The 1- and 2-year OS rates in the SR group were 92.0% and 79.9%, respectively, whereas those in the non-SR group were 85.5% and 39.6 %, respectively (p = 0.007); however, there was no significant difference in the PFS rates. Upon further stratification, OS and PFS were significantly better in the SR group than in the non-SR group in patients who were assessed as partial responses (PR), while there was no significant difference in patients who were assessed as complete response (CR). CONCLUSIONS: Salvage surgery is recommended and is associated with a favorable prognosis for uHCC patients who were assessed as PR after conversion therapy, however it may not be necessary for uHCC if CR was achieved.
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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Compuestos de Fenilurea , Quinolinas , Humanos , Carcinoma Hepatocelular/terapia , Estudios Retrospectivos , Neoplasias Hepáticas/terapia , Respuesta Patológica CompletaRESUMEN
Therapies for patients with unresectable hepatocellular carcinoma (uHCC) are currently popular. Current first-line standard-of-care treatments for uHCC are systematic therapies. However, treatments that combine locoregional therapy with systemic therapy are widely accepted in China and have demonstrated high rates of tumor response and conversion to resection with manageable toxicity. A literature review was performed by searching published literature in PubMed and Web of Science up to December 2023 for relevant articles on the use of triple therapy (transarterial chemoembolization combined with lenvatinib and anti-PD-1 antibodies) in uHCC. This review concentrates on the efficacy and safety of triple therapy with Chinese characteristics in patients with uHCC and describes the outcome of conversion surgery, degree of pathological necrosis, and effect prediction. This article will contribute to a comprehensive understanding of the role of triple therapy with Chinese characteristics in patients with uHCC.
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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Compuestos de Fenilurea , Quinolinas , Humanos , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , ChinaRESUMEN
With the development of the Internet of Things (IoT), the use of UAV-based data collection systems has become a very popular research topic. This paper focuses on the energy consumption problem of this system. Genetic algorithms and swarm algorithms are effective approaches for solving this problem. However, optimizing UAV energy consumption remains a challenging task due to the inherent characteristics of these algorithms, which make it difficult to achieve the optimum solution. In this paper, a novel particle swarm optimization (PSO) algorithm called Double Self-Limiting PSO (DSLPSO) is proposed to minimize the energy consumption of the unmanned aerial vehicle (UAV). DSLPSO refers to the operational principle of PSO and incorporates two new mechanisms. The first mechanism is to restrict the particle movement, improving the local search capability of the algorithm. The second mechanism dynamically adjusts the search range, which improves the algorithm's global search capability. DSLPSO employs a variable population strategy that treats the entire population as a single mission plan for the UAV and dynamically adjusts the number of stopping points. In addition, the proposed algorithm was also simulated using public and random datasets. The effectiveness of the proposed DSLPSO and the two new mechanisms has been verified through experiments. The DSLPSO algorithm can effectively improve the lifetime of the UAV, and the two newly proposed mechanisms have potential for optimization work.
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Algoritmos , Dispositivos Aéreos No Tripulados , Movimiento , Fenómenos Físicos , InternetRESUMEN
Background: Daqu is an essential starter for baijiu brewing in China. However, the microbial enrichment and metabolic characteristics of Daqu formed at different fermentation temperatures are still unclear. Methods: High-throughput sequencing technology and the non-targeted metabolomics were used to compare the microbial communities and metabolites of Taorong-type high-temperature Daqu and middle-temperature Daqu. In this study, the relationship between microorganisms and metabolites was established. Results: The study found that the composition and metabolites of the microbial community differed due to the difference in Daqu-making temperature. The bacterial diversity of Taorong-type high-temperature Daqu was higher than that of middle-temperature Daqu, while the fungal community diversity of Taorong-type middle-temperature Daqu was higher than that of high temperature Daqu. A total of 1,034 differential metabolites were screened from the two types of Daqu, and 76 metabolites with significant differences were detected (P < 0.001 and variable importance in projection (VIP) > 1.15). Tetraacetylethylenediamine is the metabolite with the largest differential fold among the 76 differential metabolites, which can be used as a potential marker metabolite of high-temperature Daqu. Conclusion: This study helps elucidate the microbial assembly mechanisms and functional expression under different processing conditions through a further understanding of the composition and metabolic profile differences of different types of Daqu microflora in Taorong-type baijiu.
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Microbiota , Micobioma , Temperatura , Metabolómica , ChinaRESUMEN
Soluble growth stimulation expressed gene 2 (sST2) is a new generation biomarker in the diagnosis and prognosis of heart failure (HF). Here, the sST2-specific aptamers were selected from a random ssDNA library with the full length of 88 nucleotides (nt) via target-immobilized magnetic beads (MB)-based systematic evolution of ligands by exponential enrichment (SELEX) technology. After eight rounds of selection, six aptamers with the most enrichment were selected. Among, the aptamer L1 showed the high-affinity binding to sST2 with the lowest Kd value (77.3 ± 0.05 nM), which was chosen as the optimal aptamer for further molecular docking. Then, the aptamer L1 was used to construct a graphene oxide (GO) - based fluorescence resonance energy transfer (FRET) biosensor for sST2, which exhibits a linear detection range of 0.1-100 µg/ml and a detection limit of 3.7 ng/ml. The aptasensor was applied to detect sST2 in real samples, with a good correlation and agreement with the traditional enzyme-linked immunosorbent assay (ELISA) when quantitative analyzing the sST2 concentration in serum samples from HF patients. The results show that not only an efficient strategy for screening the practicable aptamer, but also a rapid and sensitive detection platform for sST2 were established.
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Aptámeros de Nucleótidos , Biomarcadores , Grafito , Insuficiencia Cardíaca , Humanos , Aptámeros de Nucleótidos/genética , Cromatografía de Afinidad , ADN de Cadena Simple , Transferencia Resonante de Energía de Fluorescencia , Insuficiencia Cardíaca/diagnóstico , Simulación del Acoplamiento Molecular , Oligonucleótidos , Técnica SELEX de Producción de Aptámeros , Biomarcadores/análisis , Receptores de Interleucina-1/análisisRESUMEN
BACKGROUND AND AIMS: Transcatheter arterial chemoembolization combined with lenvatinib and PD-1 inhibitors (triple therapy) exhibits promising efficacy for unresectable hepatocellular carcinoma (uHCC). We aimed to evaluate the prognosis of patients with uHCC who received triple therapy and develop a prognostic scoring model to identify patients who benefit the most from triple therapy. METHODS: A total of 246 patients with uHCC who received triple therapy at eight centers were included and assigned to the training and validation cohorts. Prognosis was evaluated by the Kaplan-Meier curves. The prognostic model was developed by utilizing predictors of overall survival (OS), which were identified through the Cox proportional hazards model. RESULTS: In the training cohort, the 3-year OS was 52.0%, with a corresponding progression-free survival (PFS) of 30.6%. The median PFS was 13.2 months [95% confidence interval, 9.7-16.7]. Three variables (total bilirubin ≥ 17 µmol/L, alpha-fetoprotein ≥ 400 ng/mL, and extrahepatic metastasis) were predictors of poor survival and were used for developing a prognostic model (TAE score). The 2-year OS rates in the favorable (0 points), intermediate (1 point), and dismal groups (2-3 points) were 96.9%, 61.4%, and 11.4%, respectively (p < 0.001). The PFS was also stratified according to the TAE score. These findings were confirmed in an external validation cohort. CONCLUSIONS: Triple therapy showed encouraging clinical outcomes, and the TAE score aids in identifying patients who would benefit the most from triple therapy.
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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Compuestos de Fenilurea , Quinolinas , Humanos , Carcinoma Hepatocelular/terapia , Inhibidores de Puntos de Control Inmunológico , Neoplasias Hepáticas/terapia , PronósticoRESUMEN
PURPOSE: To evaluate the effectiveness and safety of electroacupuncture (EA) using intermittent wave stimulation in enhancing facial symmetry and nerve function in chronic Bell's palsy patients. METHODS: A 6-week assessor-blinded, randomized trial followed by an 18-week observational period was conducted. Sixty individuals with chronic Bell's palsy, showing no signs of recovery after 12 months, were equally divided to receive either 18 sessions of EA using intermittent wave stimulation or Transcutaneous Electrical Stimulation (TES), administered thrice weekly over 6 weeks. The primary outcome measure was the change in the total facial nerve index (TFNI) score from baseline to Week 6, with secondary outcomes including TFNI scores at Weeks 12 and 24, as well as the change in Sunnybrook Facial Grading System (SFG) score from baseline to Week 6, and SFG scores at Weeks 12 and 24. RESULTS: The EA group showed a significant improvement, with a mean total facial nerve index score increase of 24.35 (4.77) by Week 6 compared with 14.21 (5.12) in the Transcutaneous Electrical Stimulation group (P<.001). This superiority persisted during the 24-week follow-up. While no significant difference was observed in the Sunnybrook Facial Grading System score change from baseline to Week 6, variations were noted at Weeks 12 and 24. No major adverse effects were reported. CONCLUSION: EA with intermittent wave stimulation notably enhanced facial symmetry in chronic Bell's palsy patients over Transcutaneous Electrical Stimulation by Week 6, maintaining this edge throughout the follow-up.
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Parálisis de Bell , Electroacupuntura , Humanos , Parálisis de Bell/terapia , Parálisis de Bell/diagnóstico , Nervio Facial , Proyectos de Investigación , CaraRESUMEN
Background: This study aimed to determine whether salvage hepatectomy offers prognostic advantages for unresectable hepatocellular carcinoma (uHCC) patients with clinical complete response (cCR) after conversion therapy. Methods: A total of 74 consecutive uHCC patients with cCR after conversion therapy at seven major cancer centers in China between October 2018 and December 2021 were included. One-to-one propensity score matching (PSM) was performed to minimize the influence of potential confounders. Disease-free survival (DFS) and overall survival (OS) rates were compared between the surgical group and the non-surgical group. Results: Before PSM, 45 patients received salvage hepatectomy, and 29 patients received nonsurgical treatment. The 1-, 2-, and 3-year DFS rates were 77.8%, 61.5%, and 61.5% in the surgical group and 81.2%, 60.9%, and 60.9% in the non-surgical group, respectively. The 1-, 2-, and 3-year OS rates were 92.9%, 92.9%, and 69.7% in the surgical group and 100%, 70%, and 70% in the non-surgical group, respectively. There were no statistical differences in DFS and OS between groups [hazard ratio (HR)=0.715, 95% confidence interval (CI): 0.250-2.043, p=0.531; HR=0.980, 95% CI: 0.177-5.418, p=0.982, respectively]. After PSM, 26 pairs of patents were selected; there remained no significant differences in DFS and OS between these two groups (HR=1.547, 95% CI: 0.512-4.669, p=0.439; HR=1.024, 95% CI: 0.168-6.242, p=0.979, respectively). Conclusion: Through the study, it tend to show that salvage hepatectomy may be not essential for uHCC patients with cCR, especially for patients with a high risk of surgical complications. Prospective trials with long term follow-up are warranted to evaluate this treatment option.
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Background and objective: Mild cognitive impairment (MCI) is a cognitive dysfunction syndrome defined mostly by memory or other cognitive impairments, and may serve as a precursor to Alzheimer's disease (AD). In recent years, acupuncture has gained recognition as a potential intervention for MCI, attracting significant attention as a promising and well-established therapy. In this study, we critically evaluate the clinical efficacy and safety of an innovative acupuncture approach, termed "Kidney Nourishment and Spirit Regulation", as a therapeutic modality for MCI in geriatric populations. Methods: A prospective, randomized, single-blind, placebo-controlled, single-center clinical trial design where patients will be allocated in acupuncture, placebo (sham acupuncture sessions), or blank for eight weeks. The blank group will receive health education over the same eight-week period and will be offered compensatory acupuncture therapy after this period. The selected acupoints for this investigation include GV20, EX-HN1, GV24, GV29, CV6, CV4, PC6, KI3, LI4, LR3, HT7 and SP6. The primary outcome measure will be the Montreal Cognitive Assessment (MoCA), while secondary outcomes include the Mini Mental State Examination (MMSE), Activity of Daily Living (ADL), and Electroencephalogram (EEG). Discussion: This study seeks to provide an optimum regimen for acupuncture therapy in elderly MCI patients and to provide considerable theoretical evidence for its popularization and future broad adoption. We thus postulate that the current trial data might enlighten and potentially guide future research in terms of study design refinement.
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Background: The long-term prognosis after surgery of patients with hepatocellular carcinoma (HCC) and extrahepatic bile duct tumor thrombus (Ex-BDTT) remains unknown. We aimed to identify the surgical outcomes of patients with HCC and Ex-BDTT. Methods: A total of 138 patients with Ex-BDTT who underwent hepatectomy with preservation of the extrahepatic bile duct from five large hospitals in China between January 2009 and December 2017 were included. The Cox proportional hazards model was used to analyze overall survival (OS) and recurrence-free survival (RFS). Results: With a median follow-up of 60 months (range, 1-127.8 months), the median OS and RFS of the patients were 28.6 and 8.9 months, respectively. The 1-, 3-, and 5-year OS rates of HCC patients with Ex-BDTT were 71.7%, 41.2%, and 33.5%, respectively, and the corresponding RFS rates were 43.5%, 21.7%, and 20.0%, respectively. Multivariate analysis identified that major hepatectomy, R0 resection, and major vascular invasion were independent prognostic factors for OS and RFS. In addition, preoperative serum total bilirubin ≥ 4.2 mg/dL was an independent prognostic factor for RFS. Conclusion: Major hepatectomy with preservation of the extrahepatic bile duct can provide favorable long-term survival for HCC patients with Ex-BDTT.
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Deoxynivalenol (DON), one of the most polluted mycotoxins in the environment and food, has been proven to have strong embryonic and reproductive toxicities. However, the effects of DON on placental impairment and effective interventions are still unclear. This study investigated the effect of ß-carotene on placental functional impairment and its underlying molecular mechanism under DON exposure. Adverse pregnancy outcomes were caused by intraperitoneal injection of DON from 13.5 to 15.5 days of gestation in mice, resulting in higher enrichment of DON in placenta than in other tissue samples. Interestingly, 0.1% ß-carotene dietary supplementation could significantly alleviate DON-induced pregnancy outcomes. Additionally, in vivo and in vitro placental barrier models demonstrated the association of DON-induced placental function impairment with placental permeability barrier disruption, angiogenesis impairment, and oxidative stress induction. Moreover, ß-carotene regulated DON-induced placental toxicity by activating the expressions of claudin 1, zonula occludens-1, and vascular endothelial growth factor-A through retinoic acid-peroxisome proliferator-activated receptor α signaling.
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PPAR alfa , Placenta , Embarazo , Femenino , Animales , Ratones , Placenta/metabolismo , PPAR alfa/metabolismo , beta Caroteno/farmacología , beta Caroteno/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Tretinoina/metabolismoRESUMEN
Most fungal viruses are RNA viruses, and no double-stranded DNA virus that infects fungi is known to date. A recent study detected DNA polymerase genes that originated from large dsDNA viruses in the genomes of basal fungi, suggestive of the existence of dsDNA viruses capable of infecting fungi. In this study, we searched for viral infection signatures in chromosome-level genome assemblies of the arbuscular mycorrhizal fungus Rhizophagus irregularis. We identified a continuous 1.5-Mb putative viral region on a chromosome in R. irregularis strain 4401. Phylogenetic analyses revealed that the viral region is related to viruses in the family Asfarviridae of the phylum Nucleocytoviricota. This viral region was absent in the genomes of four other R. irregularis strains and had fewer signals of fungal transposable elements than the other genomic regions, suggesting a recent and single insertion of a large dsDNA viral genome in the genome of this fungal strain. We also incidentally identified viral-like sequences in the genome assembly of the sea slug Elysia marginata that are evolutionally close to the 1.5-Mb putative viral region. In conclusion, our findings provide strong evidence of the recent infection of the fungus by a dsDNA virus.
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Purpose: In recent years, immune checkpoint inhibitors have been used in combination with tyrosine kinase inhibitors and local therapies, creating a new era in treating hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). However, the benefits of this triple therapy remain unclear. Thus, this study evaluated whether the combination of transarterial chemoembolization (TACE), lenvatinib, and programmed death-1 (PD-1) inhibitors (triple therapy) was effective and safe for unresectable HCC with main trunk portal vein tumor thrombus (Vp4). Patients and Methods: This study enrolled patients receiving triple therapy at four institutions between August 2018 and April 2022. Patient characteristics and course of treatment were extracted from patient records. Tumors and tumor thrombus response were evaluated using an HCC-specific modified RECIST. Kaplan-Meier curve analysis demonstrated overall survival (OS) and progression-free survival (PFS). Adverse events (AEs) were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Results: Median follow-up duration was 18 (4.0-26.3) months. Overall, 41 patients with HCC and Vp4 receiving first-line triple therapy were enrolled. The intrahepatic tumor objective response rate was 68.3%. The median OS was 21.7 (range, 2.8-30.5) months, whereas the median PFS was 14.5 (range, 1.3-27.6) months. Twelve patients received sequential resections. Resection was independently associated with favorable OS and PFS. Fever (31.7%), hypertension (26.8%), fatigue (24.4%), abnormal liver function (63.4%) and decreased appetite (21.9%) were the AEs frequently associated with treatment. No treatment-related mortality occurred. Conclusion: TACE plus lenvatinib and PD-1 inhibition was effective and tolerable for treating unresectable HCC with Vp4, with a high tumor response rate and favorable prognosis.