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1.
Sensors (Basel) ; 24(19)2024 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-39409262

RESUMEN

A fiber Bragg grating (FBG) pulse and systolic blood pressure (SBP) measurement system based on the edge-filtering method is proposed. The edge filter is the Mach-Zehnder interferometer (MZI) fabricated by two fiber couplers with a linear slope of 52.45 dBm/nm. The developed system consists of a broadband light source, an edge filter, fiber Bragg gratings (FBGs), a coarse wavelength-division multiplexer (CWDM), and signal-processing circuits based on a field-programmable gate array (FPGA). It can simultaneously measure pulse pulsations of the radial artery in the wrist at three positions: Cun, Guan and Chi. The SBP can be calculated based on the pulse transit time (PTT) principle. The measurement results compared to a standard blood pressure monitor showed the mean absolute error (MAE) and standard deviation (STD) of the SBP were 0.93 ± 3.13 mmHg. The system meets the requirements of the Association for the Advancement of Medical Instrumentation (AAMI) equipment standards. The proposed system can achieve continuous real-time measurement of pulse and SBP and has the advantages of fast detection speed, stable performance, and no compression sensation for subjects. The system has important application value in the fields of human health monitoring and medical device development.


Asunto(s)
Determinación de la Presión Sanguínea , Presión Sanguínea , Interferometría , Interferometría/instrumentación , Interferometría/métodos , Humanos , Presión Sanguínea/fisiología , Determinación de la Presión Sanguínea/instrumentación , Determinación de la Presión Sanguínea/métodos , Análisis de la Onda del Pulso/instrumentación , Análisis de la Onda del Pulso/métodos , Procesamiento de Señales Asistido por Computador , Fibras Ópticas , Diseño de Equipo
2.
Pediatr Dermatol ; 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39225276

RESUMEN

OBJECTIVES: To explore the dermoscopic features of lichen sclerosus in different parts of the external genitalia in children. METHODS: A retrospective analysis of the dermoscopic features of 42 female children with vulvar lichen sclerosus treated in the Department of Dermatology of Shanxi Children's Hospital from January 2020 to May 2023. RESULTS: Among the 42 female children, aged 3-14 years (mean: 7.24 ± 2.43 years), the duration of vulvar lichen sclerosus ranged from 3 months to 2 years (mean: 9.83 ± 4.93 months). Clinical lesions occurred in the labia minora in 18 cases (42.9%), labia majora in 38 cases (90.5%), posterior fourchette in 36 cases (85.7%), perianal area in 13 cases (31.0%), anterior fourchette in 17 cases (40.5%), clitoris in seven cases (16.7%), and interlabial sulcus in 11 cases (26.2%). Dermoscopic findings common in the labia majora included follicular keratotic plugs, cloverleaf-like structures, comedo-like openings, and linear vessels (p < .05); however, purple-red globules and patches and white linear streaks were more common in the posterior fourchette (p < .05), whereas dotted vessels were more common in the labia minora (p < .05). CONCLUSIONS: Common dermoscopic findings in pediatric vulvar lichen sclerosus were yellow-white structureless areas, white linear streaks, follicular keratotic plugs, and cloverleaf-like structures; yellow-white structureless areas and white linear streaks showed the highest specificity. The dermoscopic findings varied among different affected areas, which provides a basis for further understanding of the characteristics of different sites of vulvar lichen sclerosus in the pediatric population.

3.
Anal Chim Acta ; 1325: 343122, 2024 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-39244308

RESUMEN

BACKGROUND: Drug-induced liver injury (DILI) is the most important standard for the entrance of clinical drugs into the pharmaceutical market. The elevation of superoxide anion (O2•-) during drug metabolism can mediate apoptosis of hepatocytes and further generation of liver damage. Therefore, developing an effective imaging method for evaluating O2•- levels during DILI is of great importance. However, current reported O2•- fluorescent probes either use short excitation wavelengths or a single intensity detection system, limiting the accurate quantification of O2•- in deep tissue in vivo. RESULTS: We developed a NIR-excited ratiometric nanoprobe (CyD-UCNPs) by assembly of O2•--sensitive hemicyanine dyes (CyD) on the surface of Tm/Er-codoped upconversion nanoparticles (UCNPs) with the assistance of α-cyclodextrin, which exhibited a robust "turn-on" ratiometric sensing signal. In vitro experiments indicated that CyD-UCNPs respond well to O2•- with high selectivity. Furthermore, by taking advantage of the outstanding optical properties produced by the luminescent resonance energy transfer between the UCNPs and CyD upon the excitation of 980 nm, the ratiometric upconversion luminescence signal of CyD-UCNPs was successfully utilized to monitor the fluctuation of O2•- levels under phorbol-12-myristate-13-acetate (PMA)/cisplatin-induced oxidative stress in living cells, liver tissues, and zebrafish. More importantly, endogenous change in O2•- levels in the liver sites of mice during DILI and its prevention with L-carnitine was visualized using CyD-UCNPs. SIGNIFICANCE: This study provides a ratiometric NIR-excited imaging strategy for investigating the correlation between O2•- levels and DILI and its prevention, which is significant for early diagnosis of DILI and preclinical screening of anti-hepatotoxic drugs in vivo.


Asunto(s)
Carbocianinas , Enfermedad Hepática Inducida por Sustancias y Drogas , Colorantes Fluorescentes , Rayos Infrarrojos , Nanopartículas , Superóxidos , Enfermedad Hepática Inducida por Sustancias y Drogas/diagnóstico por imagen , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Animales , Superóxidos/análisis , Superóxidos/metabolismo , Superóxidos/química , Ratones , Colorantes Fluorescentes/química , Carbocianinas/química , Nanopartículas/química , Humanos , Pez Cebra , Imagen Óptica , Transducción de Señal/efectos de los fármacos
4.
Biomed Eng Online ; 23(1): 66, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38997736

RESUMEN

BACKGROUND: Management of inferior ramus of the pubis-ischium ramus remains controversial, and related research is sparse. The main intention of this study is to describe the biomechanical and clinical outcomes of pubis-ischium ramus fractures in Tile B pelvic injuries and to identify the feasibility and necessity of fixation of the inferior ramus of the pubis-ischium ramus. METHODS: This study comprised two parts: a biomechanical test and a retrospective clinical study. For the biomechanical tests, Tile B-type pelvic injuries were modeled in six cadaver specimens by performing pubis-ischium osteotomies and disruption of the anterior and interosseous sacroiliac ligaments. The superior and/or inferior rami of the pubis-ischium ramus were repaired with reconstruction plates and separated into three groups (A, B, and C). Specimens were placed in the standing position and were loaded axially with two-leg support for three cycles at 500 N. The displacements of sacroiliac joints at osteotomy were measured with Vernier calipers and compared using statistical software. To investigate the clinical outcomes of this technique, 26 patients were retrospectively analyzed and divided into a superior ramus fixation group (Group D) and a combined superior and inferior ramus of the pubis-ischium ramus fixation group (Group E). The main outcome measures were time of operation, blood loss, postoperative radiographic reduction grading, and functional outcomes. RESULTS: In the vertical loading test, Group E showed better pelvic ring stability than Group D (P < 0.05). However, the shift of the sacroiliac joints was almost identical among the three groups. In our clinical case series, all fractures in Group E achieved bony union. Group E demonstrated earlier weight-bearing functional exercise (2.54 ± 1.45 vs 4.77 ± 2.09; P = 0.004), earlier bony union (13.23 ± 2.89 vs 16.55 ± 3.11; P = 0.013), and better functional outcomes (89.77 ± 7.27 vs 82.38 ± 8.81; P = 0.028) than Group D. The incidence of sexual dysfunction was significantly lower in Group E than that in Group D (2/13 vs 7/13; P = 0.039). Bone nonunion occurred in two patients in Group D, and two patients in Group E had heterotopic ossification. None of the patients exhibited wound complications, infections, implant failures, or bone-implant interface failures. CONCLUSIONS: Fixation of the inferior ramus of a pubis-ischium ramus fracture based on conventional fixation of the anterior pelvic ring is mechanically superior in cadaveric Tile B pelvic injury and shows rapid recovery, good functional outcomes, and low incidence of complications.


Asunto(s)
Placas Óseas , Huesos Pélvicos , Humanos , Fenómenos Biomecánicos , Masculino , Femenino , Adulto , Huesos Pélvicos/cirugía , Huesos Pélvicos/lesiones , Huesos Pélvicos/diagnóstico por imagen , Persona de Mediana Edad , Fenómenos Mecánicos , Cadáver , Fracturas Óseas/cirugía , Estudios Retrospectivos , Fijación Interna de Fracturas/instrumentación
5.
Talanta ; 279: 126599, 2024 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-39084039

RESUMEN

Drug-induced liver injury (DILI) poses a significant risk to human health. Increasing evidence indicates that the superoxide anion (O2•-), as the precursor of the other reactive oxygen species, is key in the pathological processes associated with DILI. Nonetheless, understanding of the mechanisms of DILI is difficult due to the lack of an imaging tool for monitoring the fluctuation of O2•- levels during the progression of DILI. Herein, we developed an upconversion nanoprobe (Rbh-UCNs) for in vivo ratiometric tracking of endogenous O2•- in DILI. In this design, the addition of O2•- triggers the luminescent resonance energy transfer between Rbh and UCNs, which significantly enhances absorption centered at 534 nm and translates into a distinct decrease of the UCL emission at 543 nm, while the UCL emission peak at 654 nm and 800 nm are not significantly affected, offering a ratiometric UCL signal for the quantitative detection of O2•-. In addition, Rbh-UCNs could effectively visualize endogenous O2•- in living cells, zebrafish, and liver tissues upon stimulation with PMA or cisplatin. More importantly, tissue imaging of the liver region of mice revealed that the fluctuation of O2•- levels is associated with DILI and the protective effect of L-carnitine against DILI. Altogether, this study provides an available method for a deeper comprehension of the mechanisms underlying DILI and accelerating the development process of hepatoprotective medicines.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas , Superóxidos , Pez Cebra , Enfermedad Hepática Inducida por Sustancias y Drogas/diagnóstico por imagen , Animales , Superóxidos/análisis , Superóxidos/metabolismo , Ratones , Humanos , Nanopartículas/química , Nanopartículas/toxicidad , Rayos Infrarrojos , Imagen Óptica , Hígado/diagnóstico por imagen , Hígado/metabolismo , Luminiscencia
6.
BMC Genom Data ; 25(1): 61, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38886663

RESUMEN

OBJECTIVES: As a traditional Chinese medicine, Lepidium apetalum is commonly used for purging the lung, relieving dyspnea, alleviating edema, and has the significant pharmacological effects on cardiovascular disease, hyperlipidemia, etc. In addition, the seeds of L. apetalum are rich in unsaturated fatty acids, sterols, glucosinolates and have a variety of biological activity compounds. To facilitate genomics, phylogenetic and secondary metabolite biosynthesis studies of L. apetalum, we assembled the high-resolution genome of L. apetalum. DATA DESCRIPTION: We completed chromosome-level genome assembly of the L. apetalum genome (2n = 32), using Illumina HiSeq and PacBio Sequel sequencing platform as well as high-throughput chromosome conformation capture (Hi-C) technique. The assembled genome was 296.80 Mb in size, 34.41% in GC content, and 23.89% in repeated sequence content, including 316 contigs with a contig N50 of 16.31 Mb. Hi-C scaffolding resulted in 16 chromosomes occupying 99.79% of the assembled genome sequences. A total of 46 584 genes and 105 pseudogenes were predicted, 98.37% of which can be annotated to Nr, GO, KEGG, TrEMBL, SwissPort, Pfam and KOG databases. The high-quality reference genome generated by this study will provide accurate genetic information for the molecular biology research of L. apetalum.


Asunto(s)
Genoma de Planta , Lepidium , Plantas Medicinales , Plantas Medicinales/genética , Lepidium/genética , Anotación de Secuencia Molecular , Cromosomas de las Plantas/genética , Genómica/métodos , Secuenciación de Nucleótidos de Alto Rendimiento , Filogenia
7.
Genes (Basel) ; 15(2)2024 01 24.
Artículo en Inglés | MEDLINE | ID: mdl-38397145

RESUMEN

Rehmannia glutinosa, a member of the Scrophulariaceae family, has been widely used in traditional Chinese medicine since ancient times. The main bioactive component of R. glutinosa is catalpol. However, the biogenesis of catalpol, especially its downstream pathway, remains unclear. To identify candidate genes involved in the biosynthesis of catalpol, transcriptomes were constructed from R. glutinosa using the young leaves of three cultivars, Beijing No. 3, Huaifeng, and Jin No. 9, as well as the tuberous roots and adventitious roots of the Jin No. 9 cultivar. As a result, 71,142 unigenes with functional annotations were generated. A comparative analysis of the R. glutinosa transcriptomes identified over 200 unigenes of 13 enzymes potentially involved in the downstream steps of catalpol formation, including 9 genes encoding UGTs, 13 for aldehyde dehydrogenases, 70 for oxidoreductases, 44 for CYP450s, 22 for dehydratases, 30 for decarboxylases, 19 for hydroxylases, and 10 for epoxidases. Moreover, two novel genes encoding geraniol synthase (RgGES), which is the first committed enzyme in catalpol production, were cloned from R. glutinosa. The purified recombinant proteins of RgGESs effectively converted GPP to geraniol. This study is the first to discover putative genes coding the tailoring enzymes mentioned above in catalpol biosynthesis, and functionally characterize the enzyme-coding gene in this pathway in R. glutinosa. The results enrich genetic resources for engineering the biosynthetic pathway of catalpol and iridoids.


Asunto(s)
Monoterpenos Acíclicos , Glucósidos Iridoides , Plantas Medicinales , Rehmannia , Plantas Medicinales/genética , Rehmannia/genética , Rehmannia/metabolismo , Perfilación de la Expresión Génica
8.
J Cancer ; 14(15): 2784-2797, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37781074

RESUMEN

Background: Lung cancer is a highly malignant disease, primarily due to its propensity for metastasis. AMP-activated protein kinase (AMPK), the principal downstream effector of Liver Kinase B1 (LKB1), orchestrates a broad spectrum of molecular targets, thereby constraining tumor invasion and metastasis. In parallel, the RNA-binding protein RBMS3 (RNA-binding motif, single-stranded-interacting protein 3) plays a pivotal role in the epithelial-mesenchymal transition (EMT), a pivotal process in tumorigenesis. Therefore, our research aims to clarify the important role of RBMS3 as a mediator in the LKB1/AMPK inhibition of tumor invasion and metastasis. Methods: We investigated the expression and correlation between RBMS3 and LKB1 in lung cancer tissues utilizing immunohistochemistry and TCGA-LUAD data, respectively. The relationship between RBMS3 and clinical pathological features and prognosis of lung cancer was also analyzed. The functions of RBMS3 in lung cancer cell proliferation, invasion, and migration were investigated in real-time in vitro. Additionally, we investigated the effects of AMPK agonists and inhibitors to explore the mediating role of RBMS3 in AMPK-induced inhibition of lung cancer invasion and migration. Results: The IHC and TCGA data both revealed low expression of RBMS3 in lung cancer. Moreover, we found that low expression of RBMS3 was positively associated with lung cancer's histological grade, clinical stage, and N stage. Additionally, low RBMS3 expression was associated with poor overall survival. Cox regression analysis revealed that RBMS3 was an independent prognostic factor for lung cancer patients. In vitro experiments verified that RBMS3 inhibited lung cancer cell proliferation, invasion, and migration. Furthermore, our findings suggested that RBMS3 played an essential role in mediating AMPK's inhibitory effect on lung cancer invasion and migration. Conclusion: Our study highlights a novel mechanism by which LKB1/AMPK pathway activation inhibits lung cancer invasion and metastasis by promoting RBMS3 expression, offering insights in developing innovative lung cancer therapies.

10.
J Cell Sci ; 136(12)2023 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-37283026

RESUMEN

Proper microtubule dynamics are critical for neuronal morphogenesis and functions, and their dysregulation results in neurological disorders and regeneration failure. Superior cervical ganglion-10 (SCG10, also known as stathmin-2 or STMN2) is a well-known regulator of microtubule dynamics in neurons, but its functions in the peripheral nervous system remain largely unknown. Here, we show that Scg10 knockout mice exhibit severely progressive motor and sensory dysfunctions with significant sciatic nerve myelination deficits and neuromuscular degeneration. Additionally, increased microtubule stability, shown by a significant increase in tubulin acetylation and decrease in tubulin tyrosination, and decreased axonal transport were observed in Scg10 knockout dorsal root ganglion (DRG) neurons. Furthermore, SCG10 depletion impaired axon regeneration in both injured mouse sciatic nerve and cultured DRG neurons following replating, and the impaired axon regeneration was found to be induced by a lack of SCG10-mediated microtubule dynamics in the neurons. Thus, our results highlight the importance of SCG10 in peripheral axon maintenance and regeneration.


Asunto(s)
Axones , Tubulina (Proteína) , Animales , Ratones , Axones/fisiología , Ganglios Espinales , Regeneración Nerviosa/genética , Neuronas , Estatmina/genética
11.
Mol Cell ; 83(8): 1197-1199, 2023 04 20.
Artículo en Inglés | MEDLINE | ID: mdl-37084709

RESUMEN

We talk to the Ji lab about their paper, "RNA Pol II preferentially regulates ribosomal protein expression by trapping disassociated subunits" (in this issue), lessons from their scientific journey so far, and what inspires them along their scientific paths.


Asunto(s)
ARN Polimerasa II , Ribosomas , ARN Polimerasa II/metabolismo , Ribosomas/metabolismo , Transcripción Genética
12.
Mol Cell ; 83(8): 1280-1297.e11, 2023 04 20.
Artículo en Inglés | MEDLINE | ID: mdl-36924766

RESUMEN

RNA polymerase II (RNA Pol II) has been recognized as a passively regulated multi-subunit holoenzyme. However, the extent to which RNA Pol II subunits might be important beyond the RNA Pol II complex remains unclear. Here, fractions containing disassociated RPB3 (dRPB3) were identified by size exclusion chromatography in various cells. Through a unique strategy, i.e., "specific degradation of disassociated subunits (SDDS)," we demonstrated that dRPB3 functions as a regulatory component of RNA Pol II to enable the preferential control of 3' end processing of ribosomal protein genes directly through its N-terminal domain. Machine learning analysis of large-scale genomic features revealed that the little elongation complex (LEC) helps to specialize the functions of dRPB3. Mechanistically, dRPB3 facilitates CBC-PCF11 axis activity to increase the efficiency of 3' end processing. Furthermore, RPB3 is dynamically regulated during development and diseases. These findings suggest that RNA Pol II gains specific regulatory functions by trapping disassociated subunits in mammalian cells.


Asunto(s)
ARN Polimerasa II , Transcripción Genética , Animales , ARN Polimerasa II/metabolismo , Proteínas Ribosómicas/genética , Proteínas Ribosómicas/metabolismo , Ribosomas/metabolismo , Subunidades de Proteína/genética , Mamíferos/metabolismo
13.
Food Funct ; 14(4): 1884-1896, 2023 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-36723004

RESUMEN

Acetaminophen (APAP)-induced liver injury (AILI) has become a growing public health problem. Ferroptosis, an iron-dependent form of cell death associated with lipid peroxide accumulation, has been recently implicated in AILI. The activation of the Nrf2 signaling pathway is a potential therapy for AILI. Kaempferol (KA), a flavonoid widely existing in edible plants, has been reported to exert profound anti-inflammatory and antioxidant activities. This study aimed to investigate whether KA exerts anti-AILI effects via the Nrf2 signaling pathway. Mice were fasted for 22 h and injected intraperitoneally with APAP (250 mg kg-1) to induce AILI. Mice were pre-injected intragastrically with KA for 2 h followed by APAP injection. The hepatic injury was observed by H&E staining. Biochemical parameters of the serum and liver were measured using kits. KA alleviated hepatic injury and inflammatory response in AILI mice and ameliorated APAP-induced hepatic iron overload and oxidative stress in mice. In addition, the protective effects of KA against APAP-induced hepatotoxicity were examined in L02 cells in vitro. Cell viability was assayed by the CCK8 assay. Mitochondrial reactive oxygen species (ROS) in L02 cells were detected by MitoSox fluorescence. KA reversed the APAP-induced decrease in cell viability and GSH levels and inhibited the accumulation of intracellular ROS. Furthermore, KA activated the Nrf2 pathway and upregulated Gpx4 in mouse livers and L02 cells to inhibit ferroptosis induced by APAP. Finally, molecular docking indicated the potential interaction of KA with Keap1. Taken together, KA ameliorated oxidative stress and ferroptosis-mediated AILI by activating Nrf2 signaling.


Asunto(s)
Enfermedad Hepática Crónica Inducida por Sustancias y Drogas , Enfermedad Hepática Inducida por Sustancias y Drogas , Ferroptosis , Animales , Ratones , Acetaminofén/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas/metabolismo , Hepatocitos/metabolismo , Quempferoles/farmacología , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Hígado/metabolismo , Ratones Endogámicos C57BL , Simulación del Acoplamiento Molecular , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo , Especies Reactivas de Oxígeno/metabolismo
14.
Acta Ophthalmol ; 101(5): 485-503, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36774646

RESUMEN

Post-laser in situ keratomileusis (post-LASIK) ectasia (PLE) is one of the most serious complications after refractive surgery, mainly manifested as progressive thinning and trembling thinning of the cornea, accompanied by increased myopia and astigmatism. The mechanisms behind mainly include genetic risk factors and external environmental factors such as eye rubbing and cornea surgery. In order to achieve the goal of reducing the incidence of ectasia, preoperative screening strategies need to be continuously improved, through the collection and assessment of genetic and environmental risk factors. Although previous preoperative screening methods did not have a uniform standard, the emergence of artificial intelligence (AI) can help us process a large amount of information and make rational use of the data. By using high-fidelity finite element modelling, differences in preoperative and postoperative strain distributions can be observed, which can predict the risk of postoperative ectasia. In this review, we describe the incidence, aetiology, prevention and treatment of PLE for the purpose of comprehensive management. In terms of treatment, corneal collagen cross-linking has been widely used to treat progressive keratoconus and other ectasia disease, either as a preventive measure during surgery or as a therapeutic modality after surgery to prevent progression of corneal dilation. Although the standard Dresden protocol has been identified as the gold standard treatment for corneal dilatation, a series of refinements, investigations and long-term studies have been conducted in recent years. Thus, understanding the factors involved in delaying the onset and slowing progression of cornea ectasia will be key to reducing the incidence worldwide.


Asunto(s)
Enfermedades de la Córnea , Queratocono , Queratomileusis por Láser In Situ , Humanos , Queratomileusis por Láser In Situ/efectos adversos , Topografía de la Córnea/métodos , Dilatación Patológica/etiología , Dilatación Patológica/prevención & control , Dilatación Patológica/diagnóstico , Inteligencia Artificial , Córnea/cirugía , Enfermedades de la Córnea/diagnóstico , Enfermedades de la Córnea/etiología , Enfermedades de la Córnea/prevención & control , Queratocono/diagnóstico , Queratocono/etiología , Queratocono/prevención & control , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos
15.
Mol Neurobiol ; 60(3): 1609-1625, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36534336

RESUMEN

Autism spectrum disorders (ASD) are highly heterogeneous neurodevelopmental disorders characterized by impaired social interaction skills. Whole exome sequencing has identified loss-of-function mutations in lysine methyltransferase 2E (KMT2E, also named MLL5) in ASD patients and it is listed as an ASD high-risk gene in humans. However, experimental evidence of KMT2E in association with ASD-like manifestations or neuronal function is still missing. Relying on KMT2E+/- mice, through animal behavior analyses, positron emission tomography (PET) imaging, and neuronal morphological analyses, we explored the role of KMT2E haploinsufficiency in ASD-like symptoms. Behavioral results revealed that KMT2E haploinsufficiency was sufficient to produce social deficit, accompanied by anxiety in mice. Whole-brain 18F-FDG-PET analysis identified that relative amygdala glycometabolism was selectively decreased in KMT2E+/- mice compared to wild-type mice. The numbers and soma sizes of amygdala neurons in KMT2E+/- mice were prominently increased. Additionally, KMT2E mRNA levels in human amygdala were significantly decreased after birth during brain development. Our findings support a causative role of KMT2E in ASD development and suggest that amygdala neuronal development abnormality is likely a major underlying mechanism.


Asunto(s)
Trastorno del Espectro Autista , Trastorno Autístico , N-Metiltransferasa de Histona-Lisina , Animales , Humanos , Ratones , Amígdala del Cerebelo/diagnóstico por imagen , Trastorno del Espectro Autista/diagnóstico por imagen , Trastorno del Espectro Autista/genética , Trastorno Autístico/genética , Conducta Animal , Haploinsuficiencia/genética , Neuronas , N-Metiltransferasa de Histona-Lisina/metabolismo
16.
Lasers Med Sci ; 38(1): 14, 2022 Dec 22.
Artículo en Inglés | MEDLINE | ID: mdl-36547739

RESUMEN

The objective of the study is to observe the changes in the effective optical zone (EOZ) after small incision lenticule extraction (SMILE) and explore possible correlations with some influencing factors. In total, 133 eyes after SMILE were divided into the mild to moderate myopia group (- 1.75 D to - 5.75 D, 70 eyes) and the high myopia group (- 6.00 D to - 9.50 D, 63 eyes). The postoperative EOZ was calculated by utilizing the corneal tangential curvature map. Changes in EOZ (△-OZ) were monitored and compared between the two groups. Pearson correlation analysis was conducted to determine the correlation between △-OZ and corneal high-order wavefront aberrations. Multicollinearity analysis and ridge regression analysis were performed to assess the correlation between △-OZ and some corneal parameters. After SMILE, the horizontal EOZ (H-EOZ), vertical EOZ (V-EOZ), and average EOZ (A-EOZ) were significantly smaller than the programmed optical zone (POZ) in both groups (p < 0.05). The difference between V-EOZ and POZ (△V-OZ) and the difference between A-EOZ and POZ (△A-OZ) showed more significant changes in the high myopia group than in the mild to moderate myopia group, and △V-OZ was significantly larger than the difference between H-EOZ and POZ (△H-OZ) in the high myopia group. In both groups, the total high-order aberration (T-HOA) and spherical aberration (SA) both increased after SMILE, and they had a similar significant negative correlation with A-EOZ. Moreover, there was a significant negative correlation between △-OZ and Km (X1), Q-value (X2), spherical equivalent (SE, X3), ablating depth (AD, X4) and △e (X6), and a significant positive correlation between △-OZ and △Q (X5). △H-OZ was expressed as Y1, △V-OZ as Y2, and △A-OZ as Y3. The multiple linear regression equations were as follows: Y1 = 3.683 - 0.065X1, Y2 = 1.549 - 0.469X2 - 0.059X3, Y3 = 4.015 - 0.07X1 - 0.03X3, Y1 = 1.337 - 0.005X4 + 0.413X5, Y2 = 1.265 + 0.469X5, and Y3 = 0.852 - 0.002X4 - 0.398X6. The correlation degree with △A-OZ was ranked as Km > △Q > Q-value > AD > e-value > △e > SE > △Km, as represented by the ridge regression analysis. The EOZ was irregularly reduced after SMILE, which should be taken into consideration in the design of POZ, especially for high myopia. Consideration of the refractive diopter and corneal topography is advised for the design of POZ, the latter of which has greater reference significance.


Asunto(s)
Cirugía Laser de Córnea , Aberración de Frente de Onda Corneal , Miopía , Humanos , Sustancia Propia/cirugía , Agudeza Visual , Córnea/cirugía , Refracción Ocular , Topografía de la Córnea , Miopía/cirugía , Láseres de Excímeros
17.
Oxid Med Cell Longev ; 2022: 8296043, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36439692

RESUMEN

Background: Myopia is a chronic ocular disease, emerging as the most common type of refractive error. This study intends to preliminarily explore the roles of protein S-nitrosylation of nitric oxide (NO) in the regulation of myopia by detecting the expression of neuronal nitric oxide synthase (nNOS) and downstream S-nitrosylation, using the animal model of lens-induced myopia (LIM) in mice. Methods: The 3-week-old C57BL/6 J mice were divided into three groups: group I, lens-induced 0-week group (take eyeballs at the age of 3 weeks); group II, self-control eyes of experimental group (take eyeballs at the age of 7 weeks); and group III, lens-induced 4-week group (take eyeballs at the age of 7 weeks). The diopter and axial length of each group were measured by streak retinoscopes and optical coherence tomography (OCT) before and after model establishment. The protein expressions and locations of nNOS and S-nitrosylated proteins (PSNOs) were measured by western blot and immunofluorescence staining. Site-specific proteomic for protein S-nitrolysation was used to detect the existence and location of S-nitrosylation proteins in the retina of myopic and nonmyopic mice. The Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and motif enrichment analyses were performed. The differential sites were analyzed by GO, KEGG, and motif. Irreversible biotinylation procedure combined with protein purification and western blot was used to detect the protein expression of α-enolase (ENO1), a key player in the hypoxia-related signal pathway. Results: The expressions of nNOS and PSNOs were significantly lower in the retina of experimental eyes than that in self-control eyes and 3-week-old baseline group. A total of 595 S-nitrosylated proteins, 709 S-nitrosylated peptides, and 708 S-nitrosylated sites were identified by site-specific S-nitrolysation proteomics in the retina of myopic and control eyes. A total of 19 differentiation loci were screened, of which 13 sites were downregulated and 6 sites were upregulated in experimental eyes compared with the self-control group. Specifically, the expression of SNO-ENO1 was significantly lower in the retina of experimental eyes than that in self-control eyes and 3-week-old baseline group. Conclusion: LIM induces the decrease of nNOS and PSNO protein levels in the retina of myopic mice. NO-mediated nonclassical protein S-nitrosylation modification may play an important role in the regulation of lens-induced myopia. ENO1 may be a key factor in the regulation of S-nitrosylation modification of myopia.


Asunto(s)
Miopía , Óxido Nítrico , Ratones , Animales , Óxido Nítrico/metabolismo , Proteómica , Ratones Endogámicos C57BL , Miopía/metabolismo , Retina/metabolismo
18.
Front Genet ; 13: 1014031, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36313450

RESUMEN

Aim: Myopia is a prevalent public health problem. The long noncoding RNA (lncRNA) mechanisms for dysregulated retinal signaling in the myopic eye have remained elusive. The aim of this study was to analyze the expression profiles and possible pathogenic roles of lncRNAs in mouse form-deprived myopia (FDM) retinas. Methods: A mouse FDM model was induced and retinas from the FDM right eyes and the contralateral eyes were collected for RNA sequencing. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and lncRNA-mRNA coexpression network analyses were conducted to explore the biological functions of the differentially expressed lncRNAs. In addition, the levels of differentially expressed lncRNAs in the myopic retinas were validated by quantitative real-time PCR (qRT-PCR). Fluorescence in situ hybridization (FISH) was used to detect the localization of lncRNAs in mouse retinas. Results: FDM eyes exhibited reduced refraction and increased ocular axial length compared to control fellow eyes. RNA sequencing revealed that there were 655 differentially expressed lncRNAs between the FDM and control retinas. Functional enrichment analysis indicated that the differentially expressed RNAs were mostly enriched in cellular processes, cytokine-cytokine receptor interactions, retinol metabolism, and rhythmic processes. Differentially expressed lncRNAs were validated by qRT-PCR. Additionally, RNA FISH showed that XR_384718.4 (Gm35369) localized in the ganglion cell (GCL) and inner nuclear layers (INL). Conclusion: This study identified the differential expression profiles of lncRNAs in myopic mouse retinas. Our results provide scientific evidence for investigations of myopia and the development of putative interventions in the future.

19.
iScience ; 25(9): 105011, 2022 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-36117989

RESUMEN

CTCF is a predominant insulator protein required for three-dimensional chromatin organization. However, the roles of its insulation of enhancers in a 3D nuclear organization have not been fully explained. Here, we found that the CTCF DNA-binding domain (DBD) forms dynamic self-interacting clusters. Strikingly, CTCF DBD clusters were found to incorporate other insulator proteins but are not coenriched with transcriptional activators in the nucleus. This property is not observed in other domains of CTCF or the DBDs of other transcription factors. Moreover, endogenous CTCF shows a phenotype consistent with the DBD by forming small protein clusters and interacting with CTCF motif arrays that have fewer transcriptional activators bound. Our results reveal an interesting phenomenon in which CTCF DBD interacts with insulator proteins and selectively localizes to nuclear positions with lower concentrations of transcriptional activators, providing insights into the insulation function of CTCF.

20.
Front Psychol ; 13: 922108, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36059759

RESUMEN

The market for sex robots is on the rise with the development of human-computer interaction. However, most sex robots on the market are presented as male-friendly products. This issue may limit and hinder females' adoption and utilization of sex robots. This paper was to take females as the research subjects exploring and verifying several concerns based on previous theories and to conduct primary research and quantitative method to investigate: (i) how females differently perceive same-gender and heterogender sex robots; (ii) their attitudes and the knowledge or definition of sex robots; and (iii) their intention of adopting heterogender robots. This study confirmed several previous theories and provided new findings and insights. Females are more likely to feel threatened by the presence of same-gender sex robots. Their negative attitudes are related to the way that sex robots exist. They are jealous of same-gender sex robots; nevertheless, this should not be attributed to their negative perception of sex robots since they also have positive perceptions and intentions to adopt a sex robot. They define sex robots more as sexual products than as engaging in the prostitution industry.

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