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This study delves into the molecular intricacies of hypopharyngeal squamous cell carcinoma (HSCC), specifically focusing on the pivotal role played by ETS translocation variant 4 (ETV4) in aerobic glycolysis. The objective is to uncover new targets for early diagnosis and treatment of HSCC. ETV4 expression in HSCC tissues was rigorously examined, revealing its association with patient survival. Through comprehensive experimentation, we demonstrated that ETV4 activation promotes HSCC cell proliferation and invasion while inhibiting apoptosis. Furthermore, in vivo experiments confirmed the tumor-promoting effect of ETV4 activation. The study elucidated the binding of ETV4 to the NSUN2 promoter and its influence on PKM2 expression, thereby regulating glycolysis and cellular functions in HSCC.
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Histone modifications function in both cellular and viral gene expression. However, the roles of acetyltransferases and histone acetylation in parvoviral infection remain poorly understood. In the current study, we found the histone deacetylase (HDAC) inhibitor, trichostatin A (TSA), promoted the replication and transcription of parvovirus minute virus of canines (MVC). Notably, the expression of host acetyltransferases KAT5, GTF3C4, and KAT2A was increased in MVC infection, as well as H4 acetylation (H4K12ac). KAT5 is not only responsible for H4K12ac but also crucial for viral replication and transcription. The viral nonstructural protein NS1 interacted with KAT5 and enhanced its expression. Further study showed that Y44 in KAT5, which may be tyrosine-phosphorylated, is indispensable for NS1-mediated enhancement of KAT5 and efficient MVC replication. The data demonstrated that NS1 interacted with KAT5, which resulted in an enhanced H4K12ac level to promote viral replication and transcription, implying the epigenetic addition of H4K12ac in viral chromatin-like structure by KAT5 is vital for MVC replication.IMPORTANCEParvoviral genomes are chromatinized with host histones. Therefore, histone acetylation and related acetyltransferases are required for the virus to modify histones and open densely packed chromatin structures. This study illustrated that histone acetylation status is important for MVC replication and transcription and revealed a novel mechanism that the viral nonstructural protein NS1 hijacks the host acetyltransferase KAT5 to enhance histone acetylation of H4K12ac, which relies on a potential tyrosine phosphorylation site, Y44 in KAT5. Other parvoviruses share a similar genome organization and coding potential and may adapt a similar strategy for efficient viral replication and transcription.
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Lisina Acetiltransferasa 5 , Infecciones por Parvoviridae , Animales , Perros , Acetilación , Acetiltransferasas/metabolismo , Cromatina , Histona Acetiltransferasas/genética , Histona Acetiltransferasas/metabolismo , Histonas/genética , Histonas/metabolismo , Infecciones por Parvoviridae/metabolismo , Infecciones por Parvoviridae/veterinaria , Infecciones por Parvoviridae/virología , Tirosina/metabolismo , Proteínas no Estructurales Virales/genética , Proteínas no Estructurales Virales/metabolismo , Línea Celular , Enfermedades de los Perros/metabolismo , Enfermedades de los Perros/virología , Lisina Acetiltransferasa 5/metabolismoRESUMEN
BACKGROUND: Soybean mosaic disease caused by soybean mosaic virus (SMV) is one of the most devastating and widespread diseases in soybean producing areas worldwide. The WRKY transcription factors (TFs) are widely involved in plant development and stress responses. However, the roles of the GmWRKY TFs in resistance to SMV are largely unclear. RESULTS: Here, 185 GmWRKYs were characterized in soybean (Glycine max), among which 60 GmWRKY genes were differentially expressed during SMV infection according to the transcriptome data. The transcriptome data and RT-qPCR results showed that the expression of GmWRKY164 decreased after imidazole treatment and had higher expression levels in the incompatible combination between soybean cultivar variety Jidou 7 and SMV strain N3. Remarkably, the silencing of GmWRKY164 reduced callose deposition and enhanced virus spread during SMV infection. In addition, the transcript levels of the GmGSL7c were dramatically lower upon the silencing of GmWRKY164. Furthermore, EMSA and ChIP-qPCR revealed that GmWRKY164 can directly bind to the promoter of GmGSL7c, which contains the W-box element. CONCLUSION: Our findings suggest that GmWRKY164 plays a positive role in resistance to SMV infection by regulating the expression of GmGSL7c, resulting in the deposition of callose and the inhibition of viral movement, which provides guidance for future studies in understanding virus-resistance mechanisms in soybean.
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Resistencia a la Enfermedad , Regulación de la Expresión Génica de las Plantas , Glycine max , Enfermedades de las Plantas , Proteínas de Plantas , Potyvirus , Factores de Transcripción , Glycine max/virología , Glycine max/genética , Resistencia a la Enfermedad/genética , Enfermedades de las Plantas/virología , Enfermedades de las Plantas/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Potyvirus/fisiología , Potyvirus/patogenicidad , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regiones Promotoras GenéticasRESUMEN
Chiral superstructures with unique chiroptical properties that are not inherent in the individual units are essential in applications such as 3D displays, spintronic devices, biomedical sensors, and beyond. Generally, chiral superstructures are obtained by tedious procedures exploring various physical and chemical forces to break spatial symmetry during the self-assembly of discrete nanoparticles. In contrast, we herein present a simple and efficient approach to chiral superstructures by intercalating small chiral molecules into preformed achiral superstructures. As a model system, the chiral CdSe nanoplatelet (NPL) superlattice exhibits a giant and tunable optical activity with the highest g-factor reaching 3.09 × 10-2 to the excitonic transition of the NPL superlattice, nearly 2 orders of magnitude higher than that of the corresponding separated chiral NPLs. The theoretical analysis reveals that the chiral deformation in the NPL superlattice induced by the chiral perturbation of the small chiral molecules is critical to the observed huge optical activity. We anticipate that this research lays a foundation for understanding and applying chiral inorganic nanosystems.
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BACKGROUND: Resistance to immune checkpoint inhibitors (ICIs) represents a major unmet medical need in non-small cell lung cancer (NSCLC) patients. Vascular endothelial growth factor (VEGF) inhibition may reverse a suppressive microenvironment and recover sensitivity to subsequent ICIs. METHODS: This phase Ib/IIa, single-arm study, comprised dose-finding (Part A) and expansion (Part B) cohorts. Patients with ICIs-refractory NSCLC were enrolled to receive anlotinib (a multi-target tyrosine kinase inhibitor) orally (from days 1 to 14 in a 21-day cycle) and nivolumab (360 mg every 3 weeks, intravenously) on a 21-day treatment cycle. The first 21-day treatment cycle was a safety observation period (phase Ib) followed by a phase II expansion cohort. The primary objectives were recommended phase 2 dose (RP2D, part A), safety (part B), and objective response rate (ORR, part B), respectively. RESULTS: Between November 2020 and March 2022, 34 patients were screened, and 21 eligible patients were enrolled (6 patients in Part A). The RP2D of anlotinib is 12 mg/day orally (14 days on and 7 days off) and nivolumab (360 mg every 3 weeks). Adverse events (AEs) of any cause and treatment-related AEs (TRAEs) were reported in all treated patients. Two patients (9.5%) experienced grade 3 TRAE. No grade 4 or higher AEs were observed. Serious AEs were reported in 4 patients. Six patients experienced anlotinib interruption and 4 patients experienced nivolumab interruption due to TRAEs. ORR and disease control rate (DCR) was 19.0% and 76.2%, respectively. Median PFS and OS were 7.4 months (95% CI, 4.3-NE) and 15.2 months (95% CI, 12.1-NE), respectively. CONCLUSION: Our study suggests that anlotinib combined with nivolumab shows manageable safety and promising efficacy signals. Further studies are warranted. TRIAL REGISTRATION: NCT04507906 August 11, 2020.
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Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma de Pulmón de Células no Pequeñas , Inhibidores de Puntos de Control Inmunológico , Neoplasias Pulmonares , Nivolumab , Inhibidores de Proteínas Quinasas , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Resistencia a Antineoplásicos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Indoles/administración & dosificación , Indoles/efectos adversos , Indoles/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Nivolumab/administración & dosificación , Nivolumab/efectos adversos , Nivolumab/uso terapéutico , Estudios Prospectivos , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/uso terapéutico , Quinolinas/administración & dosificación , Quinolinas/efectos adversos , Quinolinas/uso terapéutico , AdolescenteRESUMEN
A zinc germanium phosphorus (ZnGeP2) crystal with a chalcopyrite structure is an efficient frequency converter in the mid-infrared region. However, point defect-induced optical absorption at the pumping wavelength (near infrared region) blocked the further application of ZnGeP2. To alleviate the absorption losses caused by point defects, in situ magnesium doping compensation was presented during the ZnGeP2 bulk crystal growth process via the vertical Bridgman method. Combined with theoretical calculations, the structural distortion of the magnesium-doped ZnGeP2 crystals in different orientations was illustrated. The thermodynamic and kinetic stability of the magnesium-doped ZnGeP2 structure were demonstrated. The transmission results indicated the improvement of transmittance within a wavelength range of 1.8-2.4 µm when doped with magnesium, which revealed the powerful ability of the appropriate dopant in optimizing near-infrared optical properties. Thus, the introduction of magnesium is a practical approach to improve the transmittance performance and extend the pumping source wavelengths of ZnGeP2 crystals.
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AIMS: We aimed to develop an effective bacterial combination that can combat Fusarium oxysporum infection in watermelon using in vitro and pot experiments. METHODS AND RESULTS: In total, 53 strains of Bacillus and 4 strains of Pseudomonas were screened. Pseudomonas strains P3 and P4 and Bacillus strains XY-2-3, XY-13, and GJ-1-15 exhibited good antagonistic effects against F. oxysporum. P3 and P4 were identified as Pseudomonas chlororaphis and Pseudomonas fluorescens, respectively. XY-2-3 and GJ-1-15 were identified as B. velezensis, and XY-13 was identified as Bacillus amyloliquefaciens. The three Bacillus strains were antifungal, promoted the growth of watermelon seedlings and had genes to synthesize antagonistic metabolites such as bacilysin, surfactin, yndj, fengycin, iturin, and bacillomycin D. Combinations of Bacillus and Pseudomonas strains, namely, XY-2-3 + P4, GJ-1-15 + P4, XY-13 + P3, and XY-13 + P4, exhibited a good compatibility. These four combinations exhibited antagonistic effects against 11 pathogenic fungi, including various strains of F. oxysporum, Fusarium solani, and Rhizoctonia. Inoculation of these bacterial combinations significantly reduced the incidence of Fusarium wilt in watermelon, promoted plant growth, and improved soil nutrient availability. XY-13 + P4 was the most effective combination against Fusarium wilt in watermelon with the inhibition rate of 78.17%. The number of leaves; aboveground fresh and dry weights; chlorophyll, soil total nitrogen, and soil available phosphorus content increased by 26.8%, 72.12%, 60.47%, 16.97%, 20.16%, and 16.50%, respectively, after XY-13 + P4 inoculation compared with the uninoculated control. Moreover, total root length, root surface area, and root volume of watermelon seedlings were the highest after XY-13 + P3 inoculation, exhibiting increases by 265.83%, 316.79%, and 390.99%, respectively, compared with the uninoculated control. CONCLUSIONS: XY-13 + P4 was the best bacterial combination for controlling Fusarium wilt in watermelon, promoting the growth of watermelon seedlings, and improving soil nutrient availability.
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Bacillus , Citrullus , Resistencia a la Enfermedad , Fusarium , Enfermedades de las Plantas , Pseudomonas , Fusarium/crecimiento & desarrollo , Citrullus/microbiología , Citrullus/crecimiento & desarrollo , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/prevención & control , Bacillus/fisiología , Bacillus/genética , Bacillus/crecimiento & desarrollo , Pseudomonas/crecimiento & desarrollo , Pseudomonas/fisiología , Antibiosis , Pseudomonas fluorescens/crecimiento & desarrollo , Plantones/crecimiento & desarrollo , Plantones/microbiología , Antifúngicos/farmacologíaRESUMEN
With the development and widespread application of electromagnetic technology, the health hazards of electromagnetic radiation have attracted much attention and concern. The effect of electromagnetic radiation on the nervous system, especially on learning, memory, and cognitive functions, is an important research topic in the field of electromagnetic biological effects. Most previous studies were conducted with rodents, which are relatively mature. As research has progressed, studies using non-human primates as experimental subjects have been carried out. Compared to rodents, non-human primates such as macaques not only have brain structures more similar to those of humans but also exhibit learning and memory processes that are similar. In this paper, we present a behavioral test system for the real-time evaluation of the working memory (WM) of macaques in a microwave environment. The system consists of two parts: hardware and software. The hardware consists of four modules: the operation terminal, the control terminal, the optical signal transmission, and detection module and the reward feedback module. The software program can implement the feeding learning task, the button-pressing learning task, and the delayed match-to-sample task. The device is useful for the real-time evaluation of the WM of macaques in microwave environments, showing good electromagnetic compatibility, a simple and reliable structure, and easy operation.
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AIMS: To examine the prevalence and associated factors of chemotherapy-related cognitive impairment (CRCI) in older breast cancer survivors (BCS). DESIGN: Systematic review. DATA SOURCES: We searched EMBASE, PubMed, PsychInfo, CINAHL, Cochrance Library, Web of Science, CNKI and SinoMed, without language restrictions, for studies published from the establishment of the database to September 2022. REVIEW METHODS: Two researchers independently examined the full texts, data extraction and quality assessment, and any discrepancies were resolved through discussion with a third reviewer. Quality of evidence was assessed using the Newcastle-Ottawa Scale and the Agency for Healthcare Research and Quality Scale. RESULTS: The seven included studies showed that the estimated prevalence of CRCI in older BCS ranged from 18.6% to 27% on objective neuropsychological tests and from 7.6% to 49% on subjective cognitive assessments. The areas most affected were attention, memory, executive functioning and processing speed. CRCI was associated with 10 factors in six categories, including sociodemographic (e.g. age, education level), physiological (e.g. sleep disorders, fatigue and comorbidities), psychological (e.g. anxiety, depression), treatment modalities (e.g. chemotherapy cycles, chemotherapy regimens), genetic (e.g. APOE2, APOE4) and lifestyle factor (e.g. physical inactivity). CONCLUSION: CRCI is multifactorial and has a relatively high prevalence. However, the results of subjective and objective cognitive examinations were inconsistent, possibly due to variations in tools used to evaluate different definitions of CRCI. Nevertheless, as there are few published studies of older BCS, this conclusion still require verification by well-designed studies in the future. IMPACT: We found that the prevalence of CRCI in older adults is relatively high and multifactorial, providing evidence for further health care for this population. NO PATIENT OR PUBLIC CONTRIBUTION: There was no patient or public involvement.
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Neoplasias de la Mama , Supervivientes de Cáncer , Deterioro Cognitivo Relacionado con la Quimioterapia , Estados Unidos , Humanos , Anciano , Femenino , Prevalencia , Neoplasias de la Mama/tratamiento farmacológico , Estilo de VidaRESUMEN
AIM: To pool existing studies to assess the overall effectiveness of integrated care for older adults (ICOPE)-based interventions in improving depressive symptoms in older adults. DESIGN: A systematic review and meta-analysis. DATA SOURCES: Ten databases were systematically searched from inception to 15 July 2023 and the search was last updated on 2 September 2023. METHODS: Standardized mean difference (SMD) was calculated using random effects models. RoB 2 and GRADEpro GDT were used to assess the methodological quality and confidence in the cumulative evidence. Funnel plots, egger's test and begg's test were used to analyse publication bias. Sensitivity, subgroup and meta-regression analyses were performed to explore potential sources of heterogeneity. RESULTS: The results of 18 studies showed ICOPE-based interventions had a significant effect on improving depressive symptoms (SMD = -.84; 95% CI, -1.20 to -.3647; p < .001; 18 RCTs, 5010 participants; very low-quality evidence). Subgroup analysis showed the intervention group was characterized by mean age (70-80 years old), intervention duration between 6 to 12 months, gender (female <50%), non-frail older adults, depressed older adults and mixed integration appeared to be more effective. Sensitivity analysis found the results to be robust. CONCLUSION: ICOPE-based interventions may be a potentially effective alternative approach to reduce depressive symptoms in the older adults. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Healthcare professionals are expected to use ICOPE as one of the interventions for depressive symptoms in older adults, and this ICOPE could provide more comprehensive care services for older adults to reduce depressive symptoms. IMPACT: ICOPE-based interventions may be a potentially effective alternative approach to reduce depressive symptoms in the older adults. ICOPE-based interventions had a significant effect on reducing depressive symptoms in the older adults. The intervention group characterized by mean age of older adults, intervention duration, gender ratio, health condition and integration types may influence the effect size. REPORTING METHOD: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution.
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Prestación Integrada de Atención de Salud , Depresión , Humanos , Anciano , Depresión/terapia , Anciano de 80 o más Años , Femenino , MasculinoRESUMEN
Insufficient accumulation of lipid nanoparticles (LNPs)-based mRNA vaccines in antigen presenting cells remains a key barrier to eliciting potent antitumor immune responses. Herein, we develop dendritic cells (DCs) targeting LNPs by taking advantage of mannose receptor-mediated endocytosis. Efficient delivery of mRNA to DCs is achieved in vitro and in vivo utilizing the sweet LNPs (STLNPs-Man). Intramuscular injection of mRNA vaccine (STLNPs-Man@mRNAOVA ) results in a four-fold higher uptake by DCs in comparison with commercially used LNPs. Benefiting from its DCs targeting ability, STLNPs-Man@mRNAOVA significantly promotes the antitumor performances, showing a comparable therapeutic efficacy by using one-fifth of the injection dosage as the vaccine prepared from normal LNPs, thus remarkably avoiding the side effects brought by conventional mRNA vaccines. More intriguingly, STLNPs-Man@mRNAOVA exhibits the ability to downregulate the expression of cytotoxic T-lymphocyte-associated protein 4 on T cells due to the blockade of CD206/CD45 axis, showing brilliant potentials in promoting antitumor efficacy combined with immune checkpoint blockade therapy.
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Vacunas contra el Cáncer , Liposomas , Nanopartículas , Neoplasias , Humanos , Presentación de Antígeno , Vacunas de ARNm , ARN Mensajero/genética , ARN Mensajero/metabolismo , Células Dendríticas/metabolismo , Neoplasias/terapia , Neoplasias/metabolismoRESUMEN
Despite the tremendous breakthrough of immunotherapy, the low response rate and resistance of immune checkpoint inhibitors (ICIs) toward solid tumors occur frequently. A highly hypoxic tumor microenvironment (TME) provides tumor cells with high concentrations of HIF-1α and polyamines to evade immune cell destruction. Reprogramming of an immunogenic TME has exhibited a brilliant future to boost immunotherapeutic performances. Herein, a supramolecular nanomedicine (TAPP) is developed on the basis of host-guest molecular recognition and metal coordination, showing the capability to remodel the immunosuppressive TME. Tamoxifen (Tmx) and Fe3+ are encapsulated into TAPP to achieve the combination of chemotherapy and chemodynamic therapy (CDT). Tmx directly downregulates HIF-1α, and a pillar[5]arene-based macrocyclic host successfully eliminates polyamines in tumors. Enhanced immunogenic cell death is achieved by Tmx and Fe3+, and the therapeutic efficacy is further synergized by immune checkpoint blockade (ICB) therapy. This supramolecular reprogramming modality encourages cytotoxic T lymphocyte infiltration, achieving pre-eminent immune response and long-term tumor suppression.
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Calixarenos , Gastrópodos , Neoplasias , Animales , Microambiente Tumoral , Inmunoterapia , Neoplasias/tratamiento farmacológico , Línea Celular TumoralRESUMEN
In the published publication [...].
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Currently, machine-learning algorithms have been considered the most promising approach to reach a clinical diagnosis at the individual level. This study aimed to investigate whether the whole-brain resting-state functional connectivity (RSFC) metrics combined with machine-learning algorithms could be used to identify essential tremor (ET) patients from healthy controls (HCs) and further revealed ET-related brain network pathogenesis to establish the potential diagnostic biomarkers. The RSFC metrics obtained from 127 ET patients and 120 HCs were used as input features, then the Mann-Whitney U test and the least absolute shrinkage and selection operator (LASSO) methods were applied to reduce feature dimensionality. Four machine-learning algorithms were adopted to identify ET from HCs. The accuracy, sensitivity, specificity and the area under the curve (AUC) were used to evaluate the classification performances. The support vector machine, gradient boosting decision tree, random forest and Gaussian naïve Bayes algorithms could achieve good classification performances with accuracy at 82.8%, 79.4%, 78.9% and 72.4%, respectively. The most discriminative features were primarily located in the cerebello-thalamo-motor and non-motor circuits. Correlation analysis showed that two RSFC features were positively correlated with tremor frequency and four RSFC features were negatively correlated with tremor severity. The present study demonstrated that combining the RSFC matrices with multiple machine-learning algorithms could not only achieve high classification accuracy for discriminating ET patients from HCs but also help us to reveal the potential brain network pathogenesis in ET.
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Temblor Esencial , Humanos , Temblor , Teorema de Bayes , Encéfalo , Mapeo Encefálico , Imagen por Resonancia Magnética/métodosRESUMEN
Acetamide- or formamide-assisted in situ strategy is designed to synthesize carbon atom self-doped g-C3 N4 (AHCNx ) or nitrogen vacancy-modified g-C3 N4 (FHCNx ). Different from the direct copolymerization route that suffers from the problem of mismatched physical properties of acetamide (or formamide) with urea, the synthesis of AHCNx (or FHCNx ) starts from a crucial preorganization step of acetamide (or formamide) with urea via freeze drying-hydrothermal treatment so that the chemical structures as well as C-doping level in AHCNx and N-vacancy concentration in FHCNx can be precisely regulated. By using various structural characterization methods, well-defined AHCNx and FHCNx structures are proposed. At the optimal C-doping level in AHCNx or N-vacancy concentration in FHCNx , both AHCNx and FHCNx exhibit remarkably improved visible-light photocatalytic performance in oxidation of emerging organic pollutants (acetaminophen and methylparaben) and reduction of proton to H2 in comparison of unmodified g-C3 N4 . Combination of the experimental results with theoretical calculations, it is confirmed that AHCNx and FHCNx show different charge separation and transfer mechanisms, while the enhanced visible-light harvesting capacity and the localized charge distributions on HOMO and LUMO are responsible for this excellent photocatalytic redox performance of AHCNx and FHCNx .
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OBJECTIVE: To explore gamma-aminobutyric acid (GABA) and glutamate/glutamine (Glx) levels in the right thalamus of patients with episodic migraine (EM) and chronic migraine (CM) and their effects on the chronification of migraine. BACKGROUND: Migraine affects approximately 1 billion people worldwide, with 2.5%-3% of people with EM progressing to CM each year. Magnetic resonance spectroscopy studies have revealed altered GABA and Glx levels in the thalamus of patients with migraine without aura, but these neurometabolic concentrations are underexplored in the thalamus of patients with CM. METHODS: In this cross-sectional study, patients with EM and CM were recruited. Mescher-Garwood point resolved spectroscopy sequence was used to acquire neurotransmitter concentrations in the right thalamus of patients with EM and CM and matched healthy controls (HCs). RESULTS: A total of 26 patients (EM, n = 11; CM, n = 15) and 16 age- and sex-matched HCs were included in the analysis. There were significantly lower GABA+/Water levels in the right thalamus of the CM group (mean ± standard deviation: 2.27 ± 0.4 [institutional units]) than that of the HC group (2.74 ± 0.4) (p = 0.026; mean difference [MD] = -0.5 [i.u.]), and lower Glx/Cr levels in the EM group (mean ± SD: 0.11 ± < 0.1) than in the HCs (0.13 ± < 0.1) and CM group (0.13 ± < 0.1) (p = 0.023, MD < -0.1, and p = 0.034, MD < -0.1, respectively). The GABA+/Glx ratio was lower in the CM group (mean ± SD: 0.38 ± 0.1) compared to the EM group (0.47 ± 0.1) (p = 0.024; MD = -0.1). The area under the curve for GABA+/Water levels in differentiating patients with CM from HCs was 0.83 (95% confidence interval 0.68, 0.98; p = 0.004). Correlation analyses within the migraine group revealed no significant correlation between metabolite concentration levels and headache characteristics after Bonferroni correction. CONCLUSION: Reduced GABA+/Water levels and imbalance of excitation/inhibition in the right thalamus may contribute to migraine chronification.
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Glutamina , Trastornos Migrañosos , Humanos , Glutamina/análisis , Glutamina/metabolismo , Espectroscopía de Protones por Resonancia Magnética/métodos , Ácido Glutámico , Estudios Transversales , Trastornos Migrañosos/diagnóstico por imagen , Trastornos Migrañosos/metabolismo , Ácido gamma-Aminobutírico/análisis , Ácido gamma-Aminobutírico/metabolismo , Tálamo/diagnóstico por imagen , Tálamo/metabolismoRESUMEN
OBJECTIVES: To investigate the glymphatic function in patients with new daily persistent headache (NDPH) using the diffusion tensor image analysis along the perivascular space (DTI-ALPS) method. BACKGROUND: NDPH, a rare and treatment-refractory primary headache disorder, is poorly understood. There is limited evidence to suggest that headaches are associated with glymphatic dysfunction. Thus far, no studies have evaluated glymphatic function in patients with NDPH. METHODS: In this cross-sectional study conducted in the Headache Center of Beijing Tiantan Hospital, patients with NDPH and healthy controls were enrolled. All participants underwent brain magnetic resonance imaging examinations. Clinical characteristics and neuropsychological evaluation were examined in patients with NDPH. ALPS indexes for both hemispheres were measured to determine the glymphatic system function in patients with NDPH and healthy controls. RESULTS: In total, 27 patients with NDPH (14 males, 13 females; age [mean ± standard deviation (SD)]: 36.6 ± 20.6) and 33 healthy controls (15 males, 18 females; age [mean ± SD]: 36.0 ± 10.8) were included in the analysis. No significant differences between groups were observed in the left ALPS index (1.583 ± 0.182 vs. 1.586 ± 0.175, mean difference = 0.003, 95% confidence interval [CI] of difference = -0.089 to 0.096, p = 0.942), or right ALPS index (1.578 ± 0.230 vs. 1.559 ± 0.206, mean difference = -0.027, 95% CI of difference = -0.132 to 0.094, p = 0.738). Additionally, ALPS indexes were not correlated with clinical characteristics or neuropsychiatric scores. CONCLUSION: No glymphatic dysfunction was detected in patients with NDPH by means of the ALPS method. Additional studies with larger samples are needed to confirm these preliminary findings and improve the understanding of glymphatic function in NDPH.
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Sistema Glinfático , Trastornos de Cefalalgia , Masculino , Femenino , Humanos , Sistema Glinfático/diagnóstico por imagen , Estudios Transversales , Cefalea , Examen NeurológicoRESUMEN
INTRODUCTION: Although transoral endoscopic thyroidectomy (TOETVA) is widely utilized in clinical practice, some problems and restrictions still remain. Our study compared the perioperative features and early surgical efficacy of TOETVA and a modified transoral and submental endoscopic thyroidectomy (TOaST) in early stage papillary thyroid carcinoma (PTC). METHODS: The clinical data of PTC patients who underwent endoscopic thyroidectomy, including 42 modified TOaST patients and 114 traditional TOETVA patients, were retrospectively collected. Propensity score matching was employed to reduce patient selection bias. The perioperative features and early surgical efficacy data of two groups were compared. RESULTS: The operation time of the TOaST group was significantly shorter than that of the TOETVA group (150.00 ± 35.47 min vs. 168.75 ± 44.49 min; P = 0.030). Furthermore, the TOaST group required shorter days for a normal diet (3.38 ± 0.93 days vs. 4.04 ± 1.03 days; P = 0.000) and a shorter hospital stay than the TOETVA group (5.85 ± 2.17 days vs. 6.12 ± 2.01 days; P = 0.003). There was no statistical difference in complications between the two groups, but the probability of numbness of the lower lip and chin in the TOaST group was lower than that in the TOETVA group(5.12% vs. 13.04%, P = 0.321). The symptoms of mandibular numbness and hoarseness of most patients were relieved in both groups 6 months after surgery, and no abnormalities and recurrence were found in the thyroid ultrasound. All the patients were satisfied with the appearance of their surgical incision. CONCLUSION: In early stage PTC patients, TOaST had the same surgical effectiveness as traditional TOETVA but can minimize the probability of mandibular numbness and improve the perioperative quality of life.
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Cirugía Endoscópica por Orificios Naturales , Neoplasias de la Tiroides , Humanos , Cáncer Papilar Tiroideo/cirugía , Cáncer Papilar Tiroideo/patología , Tiroidectomía , Estudios Retrospectivos , Hipoestesia/cirugía , Calidad de Vida , Neoplasias de la Tiroides/cirugía , Neoplasias de la Tiroides/patologíaRESUMEN
Human males absent on the first (MOF), a histone acetyltransferase (HAT), forms male-specific lethal (MSL) and non-specific lethal (NSL), two multiprotein HATs, in cells. MSL was originally discovered in dosage compensation study in Drosophila that can specifically acetylate H4K16, while NSL can simultaneously catalyze the H4 at K5, K8, and K16 sites. However, comparative studies of the two HATs in regulating specific biological functions are rarely reported. Here, we present evidence to argue that MSL and NSL function in different ways in the epithelial-to-mesenchymal transition (EMT) process. At first, CRISPR/Cas9-mediated MSL1 (a key subunit of the MSL)-knockout (KO) and NSL3 (a key subunit of the NSL)-KO cells seem to prefer to grow in clusters. Interestingly, the former promotes cell survival and clonal formation, while the latter has the opposite effect on it. Cell staining revealed that MSL1-KO leads to multipolarized spindles, while NSL3-KO causes more lumen-like cells. Furthermore, in Transwell experiments, silencing of MSL1 promotes cell invasion in 293 T, MCF-7, and MDA-MB-231 cells. In contrast, the inhibitory effects on cell invasion are observed in the same NSL3-silenced cells. Consistent with this, mesenchymal biomarkers, like N-cadherin, vimentin, and snail, are negatively correlated with the expression level of MSL1; however, a positive relationship between these proteins and NSL3 in cells has been found. Further studies have clarified that MSL1, but not NSL3, can specifically bind to the E-box-containing Snail promoter region and thereby negatively regulate Snail transactivation. Also, silencing of MSL1 promotes the lung metastasis of B16F10 melanoma cells in mice. Finally, ChIP-Seq analysis indicated that the NSL may be mainly involved in phosphoinositide-mediated signaling pathways. Taken together, the MOF-containing MSL and NSL HATs may regulate the EMT process in different ways in order to respond to different stimuli.
Asunto(s)
Transición Epitelial-Mesenquimal , Histona Acetiltransferasas , Acetilación , Animales , Compensación de Dosificación (Genética) , Transición Epitelial-Mesenquimal/genética , Histona Acetiltransferasas/genética , Histona Acetiltransferasas/metabolismo , Humanos , RatonesRESUMEN
PURPOSE: To study the long-term natural course of myopic retinoschisis (MRS) with a dome-shaped macula (DSM) and to identify the factors affecting its development and visual prognosis. METHODS: In this retrospective case series study, we followed 25 MRS eyes with a DSM and 68 MRS eyes without a DSM for at least two years and observed changes in optical coherence tomography morphologic features and best-corrected visual acuity. RESULTS: During the mean follow-up of 48.3 ± 13.24 months, the difference in the rate of MRS progression between the DSM and non-DSM groups was not significant ( P = 0.7462). In the DSM group, the patients whose MRS progressed were older and had a higher refractive error than those whose MRS was stable or improved ( P = 0.0301 and 0.0166, respectively). The patients whose DSM was located in the central fovea had a significantly higher progression rate than those whose DSM was located in the parafovea ( P = 0.0421). For all DSM eyes, BCVA did not decrease significantly in eyes with extrafoveal retinoschisis ( P = 0.2500), patients whose best-corrected visual acuity decreased more than two lines had a greater central foveal thickness initially than those whose best-corrected visual acuity decreased less than two lines during the follow-up period ( P = 0.0478). CONCLUSION: A DSM did not delay the progression of MRS. The development of MRS in DSM eyes was associated with age, myopic degree, and DSM location. A higher schisis cavity predicted visual deterioration, and a DSM protected visual function in extrafoveal MRS eyes during the follow-up period.