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Terrestrial plants emit volatiles into the atmosphere to attract both pollinators and the enemies of herbivores, for defense. Phalaenopsis bellina is a scented orchid species in which the main scent components are monoterpenes, including linalool and geraniol, and their derivatives. Here, we investigated whether ABC transporters are involved in floral scent emission. We carried out whole-genome identification of ABC transporter-related genes using four floral transcriptomics libraries of P. bellina. We identified 86 ABC subfamily G genes related to terpenoid transport. After comparing the gene expression patterns of P. bellina with that of Phalaenopsis aphrodite subsp. formosana, a scentless species, followed by gene-to-gene correlation analysis, PbABCG1 and PbABCG2 were selected. The temporal expression of both PbABCG1 and PbABCG2 was highly correlated with that of the key enzyme PbGDPS and the major transcription factor PbbHLH4 in monoterpene biosynthesis, with optimal expression on day 5 post-anthesis. Spatial gene expression analysis showed that PbABCG1 was highly expressed in sepals, whereas PbABCG2 was expressed in the lip. Subcellular localization with a GFP fusion protein revealed that both PbABCG1 and PbABCG2 are cytoplasmic membrane proteins. Co-downregulation of PbABCG1 and PbABCG2 using both double-strand RNA interference and tobacco rattle virus-based gene silencing led to a significant decrease in monoterpene emission, accompanied by an increase in the internal monoterpene pools. Furthermore, ectopic expression of PbABCG1 and PbABCG2 in an ABC16- mutant yeast strain rescued its tolerance to geraniol. Altogether, our results indicate that PbABCG1 and PbABCG2 play substantial roles in monoterpene transport/emission in P. bellina floral scent.
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Monoterpenos , Orchidaceae , Monoterpenos/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Flores/metabolismo , Orchidaceae/genéticaRESUMEN
BACKGROUND AND AIMS: Biopterins, including tetrahydrobiopterin (BH4), dihydrobiopterin (BH2), and biopterin (B), were crucial enzyme cofactors in vivo. Despite their recognized clinical significance, there remain notable research gaps and controversies surrounding experimental outcomes. This study aims to clarify the biopterins-related issues, including analytical art, physiological intervals, and pathophysiological implications. MATERIALS AND METHODS: A novel LC-MS/MS method was developed to comprehensively profile biopterins in plasma, utilizing chemical derivatization and cold-induced phase separation. Subsequently, apparently healthy individuals were enrolled to investigate the physiological ranges. And the relationships between biopterins and biochemical indicators were analyzed to explore the pathophysiological implications. RESULTS: The developed method was validated as reliable for detecting biopterins across the entire physiological range. Timely anti-oxidation was found to be essential for accurate assessment of biopterins. The observed overall mean ± SDs levels were 3.51 ± 0.94, 1.54 ± 0.48, 2.45 ± 0.84 and 5.05 ± 1.14 ng/mL for BH4, BH2, BH4/BH2 and total biopterins. The status of biopterins showed interesting correlations with age, gender, hyperuricemia and overweight. CONCLUSION: In conjunction with proper anti-oxidation, the newly developed method enables accurate determination of biopterins status in plasma. The observed physiological intervals and pathophysiological implications provide fundamental yet inspiring support for further clinical researches.
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Biopterinas , Espectrometría de Masas en Tándem , Humanos , Biopterinas/análogos & derivados , Biopterinas/sangre , Biopterinas/metabolismo , Femenino , Masculino , Adulto , Espectrometría de Masas en Tándem/métodos , Persona de Mediana Edad , Cromatografía Liquida/métodos , Adulto Joven , Anciano , Biomarcadores/sangreRESUMEN
This work reports on the emergence of quantum Griffiths singularity (QGS) associated with the magnetic field induced superconductor-metal transition (SMT) in unconventional Nd_{0.8}Sr_{0.2}NiO_{2} infinite layer superconducting thin films. The system manifests isotropic SMT features under both in-plane and perpendicular magnetic fields. Importantly, after scaling analysis of the isothermal magnetoresistance curves, the obtained effective dynamic critical exponents demonstrate divergent behavior when approaching the zero-temperature critical point B_{c}^{*}, identifying the QGS characteristics. Moreover, the quantum fluctuation associated with the QGS can quantitatively explain the upturn of the upper critical field around zero temperature for both the in-plane and perpendicular magnetic fields in the phase boundary of SMT. These properties indicate that the QGS in the Nd_{0.8}Sr_{0.2}NiO_{2} superconducting thin film is isotropic. Moreover, a higher magnetic field gives rise to a metallic state with the resistance-temperature relation R(T) exhibiting lnT dependence among the 2-10 K range and T^{2} dependence of resistance below 1.5 K, which is significant evidence of Kondo scattering. The interplay between isotropic QGS and Kondo scattering in the unconventional Nd_{0.8}Sr_{0.2}NiO_{2} superconductor can illustrate the important role of rare region in QGS and help to uncover the exotic superconductivity mechanism in this system.
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A concise method for the facile construction of 3-methyl-2-substituted benzo[b]furans and 3-methyl-2-substituted benzo[b]thiophenes using low-cost, abundant, and easy-to-use solid calcium carbide instead of flammable and explosive gaseous acetylene as an original alkyne source, o-bromophenyl ethers or o-bromophenyl thioethers as substrates through an intramolecular carbanion-yne cyclization in a 5-exo-dig manner, and subsequent double-bond isomerization is described. The simultaneous formation of two C-C bonds is realized in a one-step route. The wide substrate scope, high yield, and simple workup manipulations are also merits of this method. The synthetic strategy can also be suitable for the gram scale.
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BACKGROUND: The reconstruction of segmental long bone defects remains one of 'The holy grails of orthopaedics'. The optimal treatment of which remains a topic of great debate. This study aimed to evaluate the outcomes following the management of critical-sized bone defects using a classification-based treatment algorithm. METHODS: A retrospective review of all patients undergoing treatment for segmental diaphyseal defects of long bones at a tertiary-level limb reconstruction unit between January 2016 and December 2021, was performed. The management of the bone defect was standardised as per the classification by Ferreira and Tanwar (2020). RESULTS: A total of 96 patients (mean age 39.8, SD 15.2) with a minimum six months follow-up were included. Most bone defects were the result of open fractures (75/96) with 67% associated with Gustilo-Anderson IIIB injuries. There was a statistical difference in the likelihood of union between treatment strategies with more than 90% of cases undergoing acute shortening and bone transport achieving union and only 72% of cases undergoing the induced membrane technique consolidating (p = 0.049). Of those defects that consolidated, there was no difference in the time to bone union between strategies (p = 0.308) with an overall median time to union 8.33 months (95% CI 7.4 - 9.2 months). The induced membrane technique was associated with a 40% risk of sepsis. CONCLUSION: This study reported the outcomes of a standardised approach to the management of critical-sized bone defects. Whilst overall results were supportive of this approach, the outcomes associated with the induced membrane technique require further refinement of its indications in the management of critical-sized bone defects.
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Fracturas Abiertas , Humanos , Estudios Retrospectivos , Adulto , Masculino , Femenino , Persona de Mediana Edad , Fracturas Abiertas/cirugía , Trasplante Óseo/métodos , Curación de Fractura , Algoritmos , Resultado del Tratamiento , Fijación Interna de Fracturas/métodos , Fracturas de la Tibia/cirugía , Adulto Joven , Procedimientos de Cirugía Plástica/métodosRESUMEN
PURPOSE: This study aimed to investigate the stability of posterior corneal surface 2 years after transepithelial photorefractive keratectomy (TPRK) in patients with a residual stromal thickness less than 350 µm. METHODS: In total, 408 eyes of 212 patients (160 women, 52 men) who underwent TPRK were enrolled in this retrospective study. All surgeries were performed in the Amaris 750S excimer laser platform with smart pulse technology. The posterior corneal elevation, anterior chamber depth, Q value, and curvature were measured using Pentacam preoperatively and postoperatively. All patients were followed up for 2 years. The relationship between percent tissue altered (PTA), age, and changes in posterior corneal surface was analyzed. RESULTS: The mean preoperative spherical equivalent was - 6.80 ± 1.18 D (range: - 9.00 to - 2.63 D). The mean residual stromal thickness was 336.46 ± 7.25 µm (range: 310-348 µm). The mean PTA was 30.93 ± 2.03% (range: 24.29-35.28%). At 2 years after surgery, the elevation of six points in the central area decreased by 1.91 ± 2.97 µm, 2.98 ± 3.23 µm, 1.17 ± 3.85 µm, 1.70 ± 2.88 µm, 1.36 ± 3.19 µm, and 1.65 ± 3.18 µm, compared with the preoperative value (P < 0.05). The elevation of three points in the peripheral area increased by 1.87 ± 6.34 µm, 0.68 ± 6.00 µm, and 0.95 ± 5.50 µm (P < 0.05). There was no significant linear relationship between PTA, age, and changes in posterior corneal surface, anterior chamber depth, and K2 (all P > 0.05). CONCLUSION: Within 2 years after TPRK, the posterior corneal surface remained stable in patients with a residual stromal thickness between 310 and 350 µm. There was no sign of iatrogenic ectasia during the follow-up period.
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Queratectomía Fotorrefractiva , Masculino , Humanos , Femenino , Estudios Retrospectivos , Topografía de la Córnea , Córnea/cirugía , Láseres de Excímeros/uso terapéuticoRESUMEN
Sex hormones, including androgens, estrogens, and progestogens, are important biomarkers for various diseases. Quantification of sex hormones is typically conducted by LC-MS/MS. At present, most methods require liquid-liquid extraction or solid phase extraction for sample preparation. However, these pretreatments are prone to compromise LC-MS/MS throughput. To improve on the current standard practices, we investigated cold-induced phase separation for sex hormone extraction. After protein precipitation with acetonitrile and adjusting the solution constitution with water, samples were stored at -30°C for 10 min to generate two distinct phases: an acetonitrile-rich layer on top of a water-rich layer. During this process, the hydrophobic sex hormones spontaneously separate into the upper layer. This simple and reliable cold-induced phase separation-based LC-MS/MS methodology was used here to simultaneously detect estrone, estradiol, estriol, testosterone, androstenedione, dehydroepiandrosterone, progesterone, and 17-hydroxyprogesterone in serum. Validation of this method indicated satisfactory performance, including acceptable linearity, accuracy, precision, and tractability. Compared with the mainstream liquid-liquid extraction-based method, this new method exhibits significant progress in throughput, which shortens the time cost of sample preparation from 90 to 40 min. We propose that this method can be an excellent alternative for sex hormone analysis in routine clinical laboratories.
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Hormonas Esteroides GonadalesRESUMEN
Quantification of steroids possesses a crucial clinical value in early diagnosis and prognosis evaluation of various endocrine diseases. However, it is still challenging to realize feasible analysis of estrogens, androgens, progestogens, and corticoids within one single workflow. In this study, two derivatization reactions were newly designed for improvement: (1) acylation of phenolic hydroxyl on estrogens with isonicotinoyl chloride (INC) under the catalysis of 4-dimethylaminopyridine and (2) post-modification of oxime hydroxyl on hydroxylamine-pretreated ketosteroids with INC. Both reactions could conduct instantaneously at room temperature under aqueous conditions. Moreover, the resulting phenolic-INC and oxime-INC esters exhibited favorable MS responses. Through integrating these derivatization strategies with cold-induced phase separation technology, a feasible LC-MS/MS method was developed for simultaneous quantification of 15 multiclass steroids with proper sample consumption (50 µL serum), satisfying sensitivity (lower limit of quantitation at 0.01-5.00 ng/mL) and high throughput (40 min for sample-preparation). The practical applicability was tested by detecting 30 real samples from pregnant and non-pregnant women. The obtained results showed a good agreement with a previous validated methodology.
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Cloruros , Oximas , Femenino , Humanos , Cromatografía Liquida , Espectrometría de Masas en Tándem/métodos , Esteroides , EstrógenosRESUMEN
Containing the largest number of species, the orchid family provides not only materials for studying plant evolution and environmental adaptation, but economically and culturally important ornamental plants for human society. Previously, we collected genome and transcriptome information of Dendrobium catenatum, Phalaenopsis equestris, and Apostasia shenzhenica which belong to two different subfamilies of Orchidaceae, and developed user-friendly tools to explore the orchid genetic sequences in the OrchidBase 4.0. The OrchidBase 4.0 offers the opportunity for plant science community to compare orchid genomes and transcriptomes and retrieve orchid sequences for further study.In the year 2022, two whole-genome sequences of Orchidoideae species, Platanthera zijinensis and Platanthera guangdongensis, were de novo sequenced, assembled and analyzed. In addition, systemic transcriptomes from these two species were also established. Therefore, we included these datasets to develop the new version of OrchidBase 5.0. In addition, three new functions including synteny, gene order, and miRNA information were also developed for orchid genome comparisons and miRNA characterization.OrchidBase 5.0 extended the genetic information to three orchid subfamilies (including five orchid species) and provided new tools for orchid researchers to analyze orchid genomes and transcriptomes. The online resources can be accessed at https://cosbi.ee.ncku.edu.tw/orchidbase5/.
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MicroARNs , Orchidaceae , Orden Génico , Bases del Conocimiento , MicroARNs/genética , Orchidaceae/genética , SinteníaRESUMEN
Organic-inorganic Hybrid (OIH) materials for multifunctional switchable applications have attracted enormous attention in recent years due to their excellent optoelectronic properties and good structural tunability. However, it still remains challenging to fabricate one simple OIH compound with multi-functionals properties, such as dielectric switching, thermochromic properties, semiconductor characteristics and ferroelasticity. Under this context, we successfully synthesized [2-(2-fluorophenyl)ethan-1- ammonium]2 SnBr6 (compound 1), which has a higher phase transition temperature of 427.7â K. Additionally, it exhibits a semiconducting property with an indirect band gap of 2.36â eV. Combining ferroelastic, narrow band gap, thermochromic, and dielectric properties, compound 1 can be considered as a rarely reported multi-functional ferroelastic material, which is expected to give inspiration for broadening the applications in the smart devices field.
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Semiconductores , Transición de FaseRESUMEN
Autophagy has been demonstrated to play important roles in the infection and pathogenesis of many viruses. We previously found that porcine parvovirus (PPV) infection can induce autophagy in porcine placental trophoblast cells (PTCs), but its underlying mechanism has not yet been fully revealed. In this study, we showed that PPV infection inhibited the activation of mTORC1 and promoted the expression of Beclin 1 and LC3II in PTCs. Treatment with a mTOR activator inhibited the expression of Beclin 1 and LC3II, as well as autophagy formation, and reduced viral replication in PPV-infected PTCs. Furthermore, we found that inhibition of AMPK expression, but not the inhibition of PI3K/Akt, p53, or MAPK/ERK1/2 pathway activation, can significantly increase mTOR phosphorylation in PPV-infected PTCs. Then, we found that the regulation of mTOR phosphorylation by AMPK was mediated by Raptor. AMPK expression knockout inhibited the activation of Raptor, decreased the expression of Beclin 1 and LC3II, suppressed the formation of autophagosomes, and reduced viral replication during PPV infection. Together, our results showed that PPV infection induces autophagy to promote viral replication by inhibiting the activation of mTORC1 through activation of the AMPK/Raptor pathway. These findings provide information to understand the molecular mechanisms of PPV-induced autophagy.
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Infecciones por Parvoviridae , Parvovirus Porcino , Rapaces , Enfermedades de los Porcinos , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Autofagia , Beclina-1 , Femenino , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Infecciones por Parvoviridae/veterinaria , Fosfatidilinositol 3-Quinasas/metabolismo , Placenta , Embarazo , Rapaces/metabolismo , Transducción de Señal , Porcinos , Serina-Treonina Quinasas TOR/metabolismo , Trofoblastos/metabolismo , Replicación ViralRESUMEN
Acromegaly is associated with significant morbidity and mortality if it is not appropriately treated. In addition to insulin-like growth factor 1 and growth hormone normalization as well as tumor shrinkage, the treatment goals include relieving symptoms, managing complications, and improving patients' quality of life. Surgical resection is a first-line treatment option for most patients, with few being pretreated preoperatively with medications. Somatostatin receptor ligands (SRLs), injectable and, more recently, oral capsules, have been the cornerstone of first-line medical therapy for persistent disease. However, several factors, including sparsely granulated adenomas, absent or low somatostatin receptor status, T2-hyperintensity imaging, young age, and aryl hydrocarbon receptor-interacting protein mutations, can predict first-generation SRL resistance. Patients with these characteristics may be better candidates for the growth hormone receptor antagonist pegvisomant, or in cases of large tumors, the second-generation SRL pasireotide. Combination therapy should be further pursued in patients who remain biochemically uncontrolled or have a high remnant tumor after monotherapy. An efficacious and cost-effective pegvisomant dose-sparing effect of SRLs when used in combination has been demonstrated. With such a wide array of medical treatment options, it is becoming increasingly important to tailor treatment to patients' unique characteristics and preferences, with a goal of personalizing management to achieve high-quality outcomes.
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Acromegalia , Adenoma , Hormona de Crecimiento Humana , Acromegalia/tratamiento farmacológico , Acromegalia/metabolismo , Adenoma/complicaciones , Adenoma/tratamiento farmacológico , Adenoma/metabolismo , Terapia Combinada , Hormona de Crecimiento Humana/uso terapéutico , Humanos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Calidad de Vida , Receptores de Somatostatina/metabolismo , Receptores de Somatostatina/uso terapéuticoRESUMEN
BACKGROUND: The study aimed to investigate the relationship between changes in corneal epithelial thickness and the outcome of myopic regression after femtosecond laser-assisted in situ keratomileusis (FS-LASIK) and transepithelial photorefractive keratectomy (TPRK). METHODS: This study included 45 eyes of 25 patients undergoing FS-LASIK and 44 eyes of 24 patients undergoing TPRK. Myopic regression occurred in these patients postoperatively from 8 to 21 months. The corneal epithelial thickness was measured using a spectral-domain optical coherence tomography at the onset of regression, 3 months after treatment, and 3 months after drug withdrawal. RESULTS: Compared with that of preoperation, corneal epithelial thickness increased when regression occurred in both groups (all P < 0.05). The thickness of central corneal epithelium in FS-LASIK and TPRK groups reached 65.02 ± 4.12 µm and 61.63 ± 2.91 µm, respectively. The corneal epithelial thickness decreased when myopic regression subsided after 3 months of steroid treatment compared to the onset (P < 0.05). With a decrease in corneal epithelial thickness, the curvature of the anterior corneal surface, central corneal thickness, and refractive power all decreased (all P < 0.05). The corneal epithelial thickness and refractive error remained relatively stable after 3 months of treatment withdrawal (P > 0.05). CONCLUSION: The corneal epithelial thickness determined the outcome of myopic regression similarly in FS-LASIK and TPRK. When the corneal epithelium thickened, regression occurred. After steroid treatment, epithelial thickness decreased whereas regression subsided.
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Esteroides , Humanos , Rayos LáserRESUMEN
Although the phytotoxicity of graphene-based materials has been investigated extensively, the effects of different graphene-based materials on nutrient uptake in plants remain unclear. Here, we analyzed the differences in phytotoxicity between single-layer graphene oxide (sGO) and multi-layer graphene oxide (mGO) by analyzing the growth status and nitrate (NO3-) accumulation in wheat plants at 0, 100, 200, 400, and 800 mg L-1 graphene oxide supply. Both sGO and mGO displayed concentration-dependent inhibitory effects on biomass, root length, number of lateral roots, and nitrogen (N) nutrient status. Treatment with 400 mg L-1 sGO caused 0.9-, 1.3-, and 1-fold higher reductions in NO3--N, assimilated N, and total N concentrations in roots, respectively, than mGO treatment. Analysis of root oxidative stress and in situ NO3- uptake revealed that sGO caused more significant damage to the root tip and a lower NO3- net influx rate than mGO. In addition, the expression of NO3- transporter (NRT) genes in roots, including NRT1.5, NRT2.1, NRT2.2, NRT2.3, and NRT2.4, under sGO treatment were lower than those under mGO treatment. Overall, sGO treatment induced a more severe inhibitory effect on root growth and NO3- uptake and accumulation than mGO treatment, accompanied by significant suppression of the expression of NRTs in sGO-treated roots. This study provides a physiological and molecular basis for studying the phytotoxic effects of various sizes of graphene oxide.
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Grafito , Triticum , Triticum/metabolismo , Nitratos/metabolismo , Grafito/metabolismo , Raíces de Plantas/metabolismo , Óxido de Magnesio , Nitrógeno/metabolismoRESUMEN
We investigate the role of each step in the combined treatment of reactive ion etching (RIE) and dynamic chemical etching (DCE) for improving the laser-induced damage resistance of fused silica optics. We employ various surface analytical methods to identify the possible damage precursors on fused silica surfaces treated with different processes (RIE, DCE, and their combination). The results show that RIE-induced defects, including F contamination, broken Si-O bonds, luminescence defects (i.e., NBOHCs and ODCs), and material densification, are potential factors that limit the improvement of laser-induced damage resistance of the optics. Although being capable of eliminating the above factors, the DCE treatment can achieve rough optical surface with masses of exposed scratches and pits which might serve as reservoirs of the deposits such as inorganic salts, thus limiting the further improvement in damage resistance of fused silica. The study guides us to a deep understanding of the laser-induced damage process in achieving fused silica optics with enhanced resistance to laser-induced damage by the combined treatment of RIE and DCE.
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PURPOSE: 68-gallium (Ga-68) ethylenediaminetetraacetic acid (EDTA) aerosols and Galligas were compared in evaluation of inhaled-particle deposition and clearance in volunteers with or without obstructive pulmonary diseases. METHODS: Nonsmoking healthy volunteers, healthy smokers, asthma patients and patients with chronic obstructive pulmonary disease (COPD) were recruited to undergo the dynamic lung ventilation positron emission tomography/computerized tomography (PET/CT) scans within two consecutive days. The inhaled particles were Ga-68-labelled carbon nanoparticles (Galligas, 30-60 nm in size) and Ga-68-labelled EDTA aerosols (1-2 µm in size), respectively. The volunteers' lung function parameters were measured for comparison. RESULTS: Central deposition and inhomogeneity of both tracers were negatively correlated with lung function parameters, including the ratio of forced expiratory volume at 1 second to forced vital capacity (FEV1 /FVC). The central or hilum deposition of Galligas, but not 68-gallium (Ga-68) EDTA, was negatively correlated with the maximal expiratory flow at 25%, 50% and 75% of the forced vital capacity. Compared with Galligas, Ga-68 EDTA aerosols were more concentrated in the central region in all groups except for the healthy nonsmokers. Ventilation inhomogeneity was more evident when using Ga-68 EDTA aerosols, especially in patients with COPD and asthma patients. In the healthy smokers, the central region accumulated more Ga-68 EDTA at 30 minutes after inhalation than immediately after inhalation. Ga-68 EDTA cleared faster in lungs than Galligas. CONCLUSIONS: Both Galligas and Ga-68 EDTA aerosols can be used for PET/CT lung ventilation scan. However, Ga-68 EDTA aerosols showed more advantages in diagnosis and evaluation of obstructive airway diseases by revealing the inhaled-particle deposition and clearance.
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Asma/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico por imagen , Ventilación Pulmonar , Adulto , Aerosoles , Asma/fisiopatología , Estudios de Casos y Controles , Ácido Edético , Femenino , Volumen Espiratorio Forzado , Radioisótopos de Galio , Humanos , Masculino , Persona de Mediana Edad , Nanopartículas , Proyectos Piloto , Estudios Prospectivos , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Capacidad VitalRESUMEN
Adult hair follicles undergo repeated cycling of regression (catagen), resting (telogen), and growth (anagen), which is maintained by hair follicle stem cells (HFSCs). The mechanism underlying hair growth initiation and HFSC maintenance is not fully understood. Here, by epithelial deletion of Hes1, a major Notch downstream transcriptional repressor, we found that hair growth is retarded, but the hair cycle progresses normally. Hes1 is specifically upregulated in the lower bulge/HG during anagen initiation. Accordingly, loss of Hes1 results in delayed activation of the secondary hair germ (HG) and shortened anagen phase. This developmental delay causes reduced hair shaft length but not identity changes in follicular lineages. Remarkably, Hes1 ablation results in impaired hair regeneration upon repetitive depilation. Microarray gene profiling on HFSCs indicates that Hes1 modulates Shh responsiveness in anagen initiation. Using primary keratinocyte cultures, we demonstrated that Hes1 deletion negatively influences ciliogenesis and Smoothened ciliary accumulation upon Shh treatment. Furthermore, transient application of Smoothened agonist during repetitive depilation can rescue anagen initiation and HFSC self-renewal in Hes1-deficient hair follicles. We reveal a critical function of Hes1 in potentiating Shh signaling in anagen initiation, which allows sufficient signaling strength to expand the HG and replenish HFSCs to maintain the hair cycle homeostasis.
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Antígenos/metabolismo , Folículo Piloso/metabolismo , Proteínas Hedgehog/metabolismo , Proteínas de Filamentos Intermediarios/metabolismo , Células Madre/metabolismo , Factor de Transcripción HES-1/metabolismo , Animales , Folículo Piloso/citología , Humanos , Ratones , Transducción de SeñalRESUMEN
BACKGROUND: N6-Methyladenosine (m6A) is the most common RNA modification and regulates RNA splicing, translation, translocation, and stability. Aberrant expression of m6A has been reported in various types of human cancers. m6A RNA modification is dynamically and reversibly mediated by different regulators, including methyltransferase, demethylases, and m6A binding proteins. However, the role of m6A RNA methylation regulators in thyroid cancer remains unknown. The aim of this study is to investigate the effect of the 13 main m6A RNA modification regulators in thyroid carcinoma. METHODS: We obtained clinical data and RNA sequencing data of 13 m6A RNA methylation regulators from The Cancer Genome Atlas (TCGA) THCA database. We performed consensus clustering to identify the clinical relevance of m6A RNA methylation regulators in thyroid carcinoma. Then we used LASSO Cox regression analysis to generate a prognostic signature based on m6A RNA modification regulator expression. Kyoto Encyclopedia of Genes and Genomes, Gene Ontology and Gene Set Enrichment Analyses were performed to explore differential cellular processes and signaling pathways between the two groups based on risk signature. RESULTS: We found that most of the m6A RNA modification regulators are down-regulated in 450 patients with thyroid carcinoma. We derived a three m6A RNA modification regulator genes-based risk signature (FTO, RBM15 and KIAA1429), that is an independent prognostic biomarker in patients with thyroid carcinoma. Moreover, we found that this risk signature could better predict outcome in male than female. Functional research in vitro demonstrated that the m6A RNA methylation regulators involved in the model acted significant role in the proliferation and migration of thyroid cancer cells. CONCLUSIONS: Our study revealed the influence of m6A RNA methylation regulators on thyroid carcinoma through biological experiments and three-gene prognostic model.
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Porcine Parvovirus (PPV), a pathogen causing porcine reproductive disorders, encodes two capsid proteins (VP1 and VP2) and three nonstructural proteins (NS1, NS2 and SAT) in infected cells. The PPV NS2 mRNA is from NS1 mRNA after alternative splicing, yet the corresponding mechanism is unclear. In this study, we identified a PPV NS1 mRNA binding protein SYNCRIP, which belongs to the hnRNP family and has been identified to be involved in host pre-mRNA splicing by RNA-pulldown and mass spectrometry approaches. SYNCRIP was found to be significantly up-regulated by PPV infection in vivo and in vitro. We confirmed that it directly interacts with PPV NS1 mRNA and is co-localized at the cytoplasm in PPV-infected cells. Overexpression of SYNCRIP significantly reduced the NS1 mRNA and protein levels, whereas deletion of SYNCRIP significantly reduced NS2 mRNA and protein levels and the ratio of NS2 to NS1, and further impaired replication of the PPV. Furthermore, we found that SYNCRIP was able to bind the 3'-terminal site of NS1 mRNA to promote the cleavage of NS1 mRNA into NS2 mRNA. Taken together, the results presented here demonstrate that SYNCRIP is a critical molecule in the alternative splicing process of PPV mRNA, while revealing a novel function for this protein and providing a potential target of antiviral intervention for the control of porcine parvovirus disease.
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ADN Viral/fisiología , Ribonucleoproteínas Nucleares Heterogéneas/genética , Infecciones por Parvoviridae/veterinaria , Parvovirus Porcino/fisiología , ARN Mensajero/genética , Enfermedades de los Porcinos/genética , Proteínas no Estructurales Virales/genética , Empalme Alternativo , Animales , Replicación del ADN , Ribonucleoproteínas Nucleares Heterogéneas/metabolismo , Infecciones por Parvoviridae/genética , Infecciones por Parvoviridae/metabolismo , Parvovirus Porcino/genética , ARN Mensajero/metabolismo , Sus scrofa , Porcinos , Enfermedades de los Porcinos/metabolismo , Proteínas no Estructurales Virales/metabolismoRESUMEN
Organic ferroelectrics are highly desirable for their light weight, mechanical flexibility and biocompatibility. However, the rational design of organic ferroelectrics has always faced great challenges. Anilinium bromide (AB) has two structures reported in the Cambridge Crystallographic Data Centre, which might be an mmmF2/m type ferroelastic (AB-1). When we studied its ferroelasticity, we were surprised to discover that there was another crystal (AB-2) in H2 O besides this one, and they were very difficult to separate. By changing the solvent, we found that AB-1 crystals could be formed in ethanol, where ferroelastic domains were visualized by polarized light microscopy, and AB-2 crystals could be obtained from various crystallization solvents of methanol, isopropanol, N-butanol, acetonitrile, dimethyl sulfoxide, and N,N-dimethylformamide, which undergo a ferroelectric phase transition with mm2Fm, showing clear ferroelectricity in two phases. To our knowledge, the regulation of ferroelasticity to ferroelectricity by solvent selective effect is unprecedented in the field of ferroelectrics. This work reveals the important role of solvent effect in organic ferroelectrics.