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1.
Nature ; 567(7747): 187-193, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30814737

RESUMEN

Dysregulation of lipid homeostasis is a precipitating event in the pathogenesis and progression of hepatosteatosis and metabolic syndrome. These conditions are highly prevalent in developed societies and currently have limited options for diagnostic and therapeutic intervention. Here, using a proteomic and lipidomic-wide systems genetic approach, we interrogated lipid regulatory networks in 107 genetically distinct mouse strains to reveal key insights into the control and network structure of mammalian lipid metabolism. These include the identification of plasma lipid signatures that predict pathological lipid abundance in the liver of mice and humans, defining subcellular localization and functionality of lipid-related proteins, and revealing functional protein and genetic variants that are predicted to modulate lipid abundance. Trans-omic analyses using these datasets facilitated the identification and validation of PSMD9 as a previously unknown lipid regulatory protein. Collectively, our study serves as a rich resource for probing mammalian lipid metabolism and provides opportunities for the discovery of therapeutic agents and biomarkers in the setting of hepatic lipotoxicity.


Asunto(s)
Metabolismo de los Lípidos/genética , Lípidos/análisis , Lípidos/genética , Proteómica , Animales , Células HEK293 , Humanos , Metabolismo de los Lípidos/fisiología , Lípidos/sangre , Lípidos/clasificación , Hígado/química , Hígado/metabolismo , Hígado/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos DBA , Obesidad/genética , Obesidad/metabolismo , Complejo de la Endopetidasa Proteasomal/química , Complejo de la Endopetidasa Proteasomal/genética , Complejo de la Endopetidasa Proteasomal/metabolismo
2.
J Cell Mol Med ; 28(9): e18352, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38685685

RESUMEN

Gliomas, the most lethal tumours in brain, have a poor prognosis despite accepting standard treatment. Limited benefits from current therapies can be attributed to genetic, epigenetic and microenvironmental cues that affect cell programming and drive tumour heterogeneity. Through the analysis of Hi-C data, we identified a potassium-chloride co-transporter SLC12A5 associated with disrupted topologically associating domain which was downregulated in tumour tissues. Multiple independent glioma cohorts were included to analyse the characterization of SLC12A5 and found it was significantly associated with pathological features, prognostic value, genomic alterations, transcriptional landscape and drug response. We constructed two SLC12A5 overexpression cell lines to verify the function of SLC12A5 that suppressed tumour cell proliferation and migration in vitro. In addition, SLC12A5 was also positively associated with GABAA receptor activity and negatively associated with pro-tumour immune signatures and immunotherapy response. Collectively, our study provides a comprehensive characterization of SLC12A5 in glioma and supports SLC12A5 as a potential suppressor of disease progression.


Asunto(s)
Neoplasias Encefálicas , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Glioma , Cotransportadores de K Cl , Simportadores , Humanos , Glioma/genética , Glioma/patología , Glioma/metabolismo , Proliferación Celular/genética , Línea Celular Tumoral , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/metabolismo , Simportadores/genética , Simportadores/metabolismo , Movimiento Celular/genética , Pronóstico , Receptores de GABA-A/metabolismo , Receptores de GABA-A/genética
3.
Opt Express ; 32(11): 18508-18515, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38859004

RESUMEN

In this study, AlGaN-based deep-ultraviolet light-emitting diodes (DUV-LEDs) processed via standard laser dicing (SLD) and multifocal laser stealth dicing (MFLSD) were investigated. Adopting the MFLSD technology would generate a roughing surface rather than the V-shaped grooves on the sidewall of 508 × 508 µm2 DUV-LEDs, which would reduce the forward operating voltage and increase the wall-plug efficiency, light output power, and far-field radiation patterns of these devices. In addition, the wavelength shift, far-field patterns, and light-tracing simulation results of the DUV-LEDs processed with SLD and MFLSD were clearly demonstrated and analyzed. Accordingly, it was observed that the MFLSD process provided more possibilities for photon escape to increase the light extraction efficiency (LEE) of DUV-LEDs, thus decreased the wavelength-redshift and junction temperature in DUV-LEDs. These results provide a reference for advanced nano-processing practices implemented during the fabrication of semiconductor devices.

4.
BMC Infect Dis ; 24(1): 2, 2024 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-38166702

RESUMEN

BACKGROUND: In the context of increasing population aging, ongoing drug-resistant pathogens and the COVID-19 epidemic, the changes in the epidemiological and clinical characteristics of patients with pneumonia remain unclear. This study aimed to assess the trends in hospitalization, case fatality, comorbidities, and isolated pathogens of pneumonia-related adult inpatients in Guangzhou during the last decade. METHODS: We retrospectively enrolled hospitalized adults who had doctor-diagnosed pneumonia in the First Affiliated Hospital of Guangzhou Medical University from January 1, 2013 to December 31, 2022. A natural language processing system was applied to automatically extract the clinical data from electronic health records. We evaluated the proportion of pneumonia-related hospitalizations in total hospitalizations, pneumonia-related in-hospital case fatality, comorbidities, and species of isolated pathogens during the last decade. Binary logistic regression analysis was used to assess predictors for patients with prolonged length of stay (LOS). RESULTS: A total of 38,870 cases were finally included in this study, with 70% males, median age of 64 (53, 73) years and median LOS of 7.9 (5.1, 12.8) days. Although the number of pneumonia-related hospitalizations showed an upward trend, the proportion of pneumonia-related hospitalizations decreased from 199.6 per 1000 inpatients in 2013 to 123.4 per 1000 in 2021, and the case fatality decreased from 50.2 per 1000 in 2013 to 23.9 per 1000 in 2022 (all P < 0.05). The most common comorbidities were chronic obstructive pulmonary disease, lung malignancy, cardiovascular diseases and diabetes. The most common pathogens were Pseudomonas aeruginosa, Candida albicans, Acinetobacter baumannii, Stenotrophomonas maltophilia, Klebsiella pneumoniae, and Staphylococcus aureus. Glucocorticoid use during hospitalization (Odd Ratio [OR] = 1.86, 95% Confidence Interval (CI): 1.14-3.06), immunosuppressant use during hospitalization (OR = 1.99, 1.14-3.46), ICU admission (OR = 16.23, 95%CI: 11.25-23.83), receiving mechanical ventilation (OR = 3.58, 95%CI: 2.60-4.97), presence of other underlying diseases (OR = 1.54, 95%CI: 1.15-2.06), and elevated procalcitonin (OR = 1.61, 95%CI: 1.19-2.19) were identified as independent predictors for prolonged LOS. CONCLUSION: The proportion of pneumonia-related hospitalizations and the in-hospital case fatality showed downward trends during the last decade. Pneumonia inpatients were often complicated by chronic underlying diseases and isolated with gram-negative bacteria. ICU admission was a significant predictor for prolonged LOS in pneumonia inpatients.


Asunto(s)
Pacientes Internos , Neumonía , Masculino , Adulto , Humanos , Femenino , Estudios Retrospectivos , Hospitalización , Neumonía/epidemiología , China/epidemiología
5.
Br J Anaesth ; 132(2): 334-342, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38044237

RESUMEN

BACKGROUND: Delayed emergence from general anaesthesia poses a significant perioperative safety hazard. Subanaesthetic doses of ketamine not only deepen anaesthesia but also accelerate recovery from isoflurane anaesthesia; however, the mechanisms underlying this phenomenon remain elusive. Esketamine exhibits a more potent receptor affinity and fewer adverse effects than ketamine and exhibits shorter recovery times after brief periods of anaesthesia. As the paraventricular thalamus (PVT) plays a pivotal role in regulating wakefulness, we studied its role in the emergence process during combined esketamine and isoflurane anaesthesia. METHODS: The righting reflex and cortical electroencephalography were used as measures of consciousness in mice during isoflurane anaesthesia with coadministration of esketamine. The expression of c-Fos was used to determine neuronal activity changes in PVT neurones after esketamine administration. The effect of esketamine combined with isoflurane anaesthesia on PVT glutamatergic (PVTGlu) neuronal activity was monitored by fibre photometry, and chemogenetic technology was used to manipulate PVTGlu neuronal activity. RESULTS: A low dose of esketamine (5 mg kg-1) accelerated emergence from isoflurane general anaesthesia (474 [30] s vs 544 [39] s, P=0.001). Esketamine (5 mg kg-1) increased PVT c-Fos expression (508 [198] vs 258 [87], P=0.009) and enhanced the population activity of PVTGlu neurones (0.03 [1.7]% vs 6.9 [3.4]%, P=0.002) during isoflurane anaesthesia (1.9 [5.7]% vs -5.1 [5.3]%, P=0.016) and emergence (6.1 [6.2]% vs -1.1 [5.0]%, P=0.022). Chemogenetic suppression of PVTGlu neurones abolished the arousal-promoting effects of esketamine (459 [33] s vs 596 [33] s, P<0.001). CONCLUSIONS: Our results suggest that esketamine promotes recovery from isoflurane anaesthesia by activating PVTGlu neurones. This mechanism could explain the rapid arousability exhibited upon treatment with a low dose of esketamine.


Asunto(s)
Anestésicos por Inhalación , Isoflurano , Ketamina , Tálamo , Animales , Ratones , Anestesia General , Anestésicos por Inhalación/farmacología , Isoflurano/farmacología , Ketamina/farmacología , Tálamo/efectos de los fármacos
6.
Mycoses ; 67(1): e13692, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38214431

RESUMEN

BACKGROUND: The role of artificial intelligence (AI) in the discrimination between pulmonary cryptococcosis (PC) and lung adenocarcinoma (LA) warrants further research. OBJECTIVES: To compare the performances of AI models with clinicians in distinguishing PC from LA on chest CT. METHODS: Patients diagnosed with confirmed PC or LA were retrospectively recruited from three tertiary hospitals in Guangzhou. A deep learning framework was employed to develop two models: an undelineated supervised training (UST) model utilising original CT images, and a delineated supervised training (DST) model utilising CT images with manual lesion annotations provided by physicians. A subset of 20 cases was randomly selected from the entire dataset and reviewed by clinicians through a network questionnaire. The sensitivity, specificity and accuracy of the models and the clinicians were calculated. RESULTS: A total of 395 PC cases and 249 LA cases were included in the final analysis. The internal validation results for the UST model showed a sensitivity of 85.3%, specificity of 81.0%, accuracy of 83.6% and an area under the curve (AUC) of 0.93. Similarly, the DST model exhibited a sensitivity of 88.2%, specificity of 88.1%, accuracy of 88.2% and an AUC of 0.94. The external validation of the two models yielded AUC values of 0.74 and 0.77, respectively. The average sensitivity, specificity and accuracy of 102 clinicians were determined to be 63.1%, 53.7% and 59.3%, respectively. CONCLUSIONS: Both models outperformed the clinicians in distinguishing between PC and LA on chest CT, with the UST model exhibiting comparable performance to the DST model.


Asunto(s)
Adenocarcinoma del Pulmón , Aprendizaje Profundo , Neoplasias Pulmonares , Humanos , Inteligencia Artificial , Estudios Retrospectivos , Adenocarcinoma del Pulmón/diagnóstico por imagen , Adenocarcinoma del Pulmón/patología , Tomografía Computarizada por Rayos X/métodos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología
7.
J Formos Med Assoc ; 123 Suppl 2: S135-S140, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38097431

RESUMEN

Unilateral primary aldosteronism is thought to be a surgically curable disease, and unilateral adrenalectomy is the mainstay treatment. The Primary Aldosteronism Surgical Outcome (PASO) consensus was developed to assess clinical and biochemical outcomes to standardize the classification of surgical outcomes. However, fewer than half of patients are cured of hypertension after adrenalectomy; therefore, preoperative patient counseling and evaluation might be necessary. Moreover, current studies show that genetic mutations and histopathology classification are associated with the treatment outcome. The Task Force of Taiwan PA recommends using a specific scoring system, including the PASO score and nomogram-based preoperative score, to predict the clinical outcome before adrenalectomy. Herein, we discuss the associations of current histopathological classification and specific somatic gene mutations with clinical outcomes after surgery.


Asunto(s)
Hiperaldosteronismo , Hipertensión , Humanos , Estudios Retrospectivos , Hiperaldosteronismo/genética , Hiperaldosteronismo/cirugía , Resultado del Tratamiento , Adrenalectomía , Hipertensión/complicaciones
8.
J Formos Med Assoc ; 123 Suppl 2: S125-S134, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37328332

RESUMEN

Primary aldosteronism (PA) is the most common cause of secondary hypertension and one of the few medical diseases that can be cured by surgery. Excessive aldosterone secretion is highly associated with cardiovascular complications. Many studies have shown that patients with unilateral PA treated with surgery have better survival, cardiovascular, clinical, and biochemical outcomes than those who receive medical treatment. Consequently, laparoscopic adrenalectomy is the gold standard for treating unilateral PA. Surgical methods should be individualized according to the patient's tumor size, body shape, surgical history, wound considerations, and surgeon's experience. Surgery can be performed through a transperitoneal or retroperitoneal approach, and via a single-port or multi-port laparoscopic approach. However, total or partial adrenalectomy remains controversial in treating unilateral PA. Partial excision will not completely eradicate the disease and is prone to recurrence. Mineralocorticoid receptor antagonists should be considered for patients with bilateral PA or patients who cannot undergo surgery. There are also emerging alternative interventions, including radiofrequency ablation and transarterial adrenal ablation, for which data on long-term outcomes are currently lacking. The Task Force of Taiwan Society of Aldosteronism developed these clinical practice guidelines with the aim of providing medical professionals with more updated information on the treatment of PA and improving the quality of care.


Asunto(s)
Hiperaldosteronismo , Hipertensión , Humanos , Taiwán , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/cirugía , Adrenalectomía/efectos adversos , Hipertensión/etiología , Hipertensión/tratamiento farmacológico , Antagonistas de Receptores de Mineralocorticoides/uso terapéutico
9.
Angew Chem Int Ed Engl ; : e202407372, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38895749

RESUMEN

Ion exchange membranes (IEMs) play a critical role in aqueous organic redox flow batteries (AORFBs). Traditional IEMs that feature microphase-separated microstructures are well developed and easily available but suffer from the conductivity/selectivity tradeoff. The emerging charged microporous polymer membranes show the potential to overcome this tradeoff, yet their commercialization is still hindered by tedious syntheses and demanding conditions. We herein combine the advantages of these two types of membrane materials via simple in-situ hypercrosslinking of conventional IEMs into microporous ones. Such a concept is exemplified by the very cheap commercial quaternized polyphenylene oxide membrane. The hypercrosslinking treatment turns poor-performance membranes into high-performance ones, as demonstrated by the above 10-fold selectivity enhancement and much-improved conductivities that more than doubled. This turn is also confirmed by the effective and stable pH-neutral AORFB with decreased membrane resistance and at least an order of magnitude lower capacity loss rate. This battery shows advantages over other reported AORFBs in terms of a low capacity loss rate (0.0017% per cycle) at high current density. This work provides an economically feasible method for designing AORFB-oriented membranes with microporosity.

10.
Angew Chem Int Ed Engl ; 63(18): e202402018, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38390636

RESUMEN

Developing ruthenium-based heterogeneous catalysts with an efficient and stable interface is essential for enhanced acidic oxygen evolution reaction (OER). Herein, we report a defect-rich ultrathin boron nitride nanosheet support with relatively independent electron donor and acceptor sites, which serves as an electron reservoir and receiving station for RuO2, realizing the rapid supply and reception of electrons. Through precisely controlling the reaction interface, a low OER overpotential of only 180 mV (at 10 mA cm-2) and long-term operational stability (350 h) are achieved, suggesting potential practical applications. In situ characterization and theoretical calculations have validated the existence of a localized electronic recycling between RuO2 and ultrathin BN nanosheets (BNNS). The electron-rich Ru sites accelerate the adsorption of water molecules and the dissociation of intermediates, while the interconnection between the O-terminal and B-terminal edge establishes electronic back-donation, effectively suppressing the over-oxidation of lattice oxygen. This study provides a new perspective for constructing a stable and highly active catalytic interface.

11.
Opt Express ; 31(22): 36547-36556, 2023 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-38017804

RESUMEN

The effects of different p-GaN layer thickness on the photoelectric and thermal properties of AlGaN-based deep-ultraviolet light-emitting diodes (DUV-LEDs) were investigated. The results revealed that appropriate thinning of the p-GaN layer enhances the photoelectric performance and thermal stability of DUV-LEDs, reducing current crowding effects that affect the external quantum efficiency and chip heat dissipation. The ABC + f(n) model was used to analyse the EQE, which helped in identifying the different physical mechanisms for DUV-LEDs with different p-GaN layer thickness. Moreover, the finite difference time domain simulation results revealed that the light-extraction efficiency of the DUV-LEDs exhibits a trend similar to that of damped vibration as the thickness of the p-GaN layer increases. The AlGaN-based DUV-LED with a p-GaN layer thickness of 20 nm exhibited the best photoelectric characteristics and thermal stability.

12.
BMC Bioinformatics ; 22(Suppl 10): 613, 2022 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-35012455

RESUMEN

BACKGROUND: Glucocorticoid-remediable aldosteronism (GRA) is a form of heritable hypertension caused by a chimeric fusion resulting from unequal crossing over between 11ß-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2), which are two genes with similar sequences. Different crossover patterns of the CYP11B1 and CYP11B2 chimeric genes may be associated with a variety of clinical presentations. It is therefore necessary to develop an efficient approach for identifying the differences between the hybrid genes of a patient with GRA. RESULTS: We developed a long-read analysis pipeline named GRAde (GRA deciphering), which utilizes the nonidentical bases in the CYP11B1 and CYP11B2 genomic sequences to identify and visualize the chimeric form. We sequenced the polymerase chain reaction (PCR) products of the CYP11B1/CYP11B2 chimeric gene from 36 patients with GRA using the Nanopore MinION device and analyzed the sequences using GRAde. Crossover events were identified for 30 out of the 36 samples. The crossover sites appeared in the region exhibiting high sequence similarity between CYP11B1 and CYP11B2, and 53.3% of the cases were identified as having a gene conversion in intron 2. More importantly, there were six cases for whom the PCR products indicated a chimeric gene, but the GRAde results revealed no crossover pattern. The crossover regions were further verified by Sanger sequencing analysis. CONCLUSIONS: PCR-based target enrichment followed by long-read sequencing is an efficient and precise approach to dissecting complex genomic regions, such as those involved in GRA mutations, which could be directly applied to clinical diagnosis. The scripts of GRAde are available at https://github.com/hsu-binfo/GRAde .


Asunto(s)
Citocromo P-450 CYP11B2 , Hiperaldosteronismo , Esteroide 11-beta-Hidroxilasa , Citocromo P-450 CYP11B2/genética , Humanos , Hiperaldosteronismo/genética , Proteínas Mutantes Quiméricas , Mutación , Esteroide 11-beta-Hidroxilasa/genética
13.
Opt Express ; 30(10): 16827-16836, 2022 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-36221517

RESUMEN

This study utilized thin p-GaN, indium tin oxide (ITO), and a reflective passivation layer (RPL) to improve the performance of deep ultra-violet light-emitting diodes (DUV-LEDs). RPL reflectors, which comprise HfO2/SiO2 stacks of different thickness to maintain high reflectance, were deposited on the DUV-LEDs with 40 nm-thick p-GaN and 12 nm-thick ITO thin films. Although the thin p-GaN and ITO films affect the operation voltage of DUV-LEDs, the highly reflective RPL structure improved the WPE and light extraction efficiency (LEE) of the DUV-LEDs, yielding the best WPE and LEE of 2.59% and 7.57%, respectively. The junction temperature of DUV-LEDs with thick p-GaN increased linearly with the injection current, while that of DUV-LEDs with thin p-GaN, thin ITO, and RPL was lower than that of the Ref-LED under high injection currents (> 500 mA). This influenced the temperature sensitive coefficients (dV/dT, dLOP/dT, and dWLP/dT). The thermal behavior of DUV-LEDs with p-GaN and ITO layers of different thicknesses with/without the RPL was discussed in detail.

14.
Opt Express ; 30(23): 42241-42248, 2022 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-36366681

RESUMEN

This study fabricated high-voltage, low-current DUV-LEDs by connecting two devices. Due to better current spreading and the enhanced reflective mirror effect, high-voltage devices present a higher dynamic resistance, emission output power, wall-plug efficiency, external quantum efficiency, and view angle than single traditional devices. The study found that when the injection current was 320 mA, the maximum output power was exhibited at 47.1 mW in the HV sample. The maximum WPE and EQE of high-voltage DUV-LEDs were 2.46% and 5.48%, respectively. Noteworthily, the redshift wavelength shifted from 287.5 to 280.5 nm, less than the traditional device-from 278 to 282 nm. Further, due to the uniform emission patterns in high-voltage devices, the view angle presents 130 degrees at 100 mA input current. In this study, the high-voltage device showed more excellent properties than the traditional device. In particular, it presented a high potential application in high-voltage circuits, which can remove transformers to eliminate extra power consumption.

15.
Opt Express ; 30(26): 47792-47800, 2022 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-36558698

RESUMEN

In this study, deep-ultraviolet light-emitting diodes (DUV LEDs) with different chip sidewall geometries (CSGs) are investigated. The structure had two types of chip sidewall designs that combined DUV LEDs with the same p-GaN thickness. By comparing the differences of the characteristics such as the external quantum efficiency droops, light output power, light extraction efficiency (LEE), and junction temperature of these DUV LEDs, the self-heated effect and light-tracing simulation results have been clearly demonstrated to explain the inclined sidewalls that provide more possibility pathway for photons escape to increase the LEE of LEDs; thus, the DUV LEDs with the CSG presented improved performance. These results demonstrate the potential of CSG for DUV LED applications.

16.
J Org Chem ; 87(5): 2446-2455, 2022 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-35080400

RESUMEN

An iodine-catalyzed synthesis of benzoazole-substituted thioenamines in a one-pot manner was reported. Using 2-aminothiophenols (or 2-aminophenols or 1,2-phenylenediamines), tetramethylthiuram disulfide (TMTD), and enamines (mainly indoles) as starting materials, the target C(sp2)-S formation products (benzoazole-substituted thioenamines) could be furnished smoothly in good yields. The reaction might proceed through an electrophilic substitution pathway in a cross dehydrogenation coupling (CDC) manner. The protocol is metal-free and features easy performance, a one-pot manner, a good functional group tolerance, and good yields.

17.
Sensors (Basel) ; 22(10)2022 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-35632087

RESUMEN

To investigate the influence of depth on the rockburst of surrounding rock in a circular tunnel, true-triaxial tests at different depths were carried out on cubic granite specimens with a circular through-going hole. A micro camera was used to monitor the rockburst process of the circular hole sidewall in real time. The test results show that the failure process at different depths can be divided into four periods: the calm period, the particle ejection period, the rock fragment exfoliation period, and the rock bursting period. With an increase in depth, the three-dimensional unequal stress state gradually increased; the failure range and the size of rock fragments increased, the initial failure vertical stress linearly increased, and the strength and stability of the surrounding rock were enhanced. Therefore, the support range of surrounding rock should be increased as the depth increased to improve the overall stability of surrounding rock and reduce the failure range.

18.
J Neurosci ; 40(37): 7027-7042, 2020 09 09.
Artículo en Inglés | MEDLINE | ID: mdl-32801152

RESUMEN

One emerging concept in neuroscience states that synaptic vesicles and the molecular machinery underlying spontaneous transmitter release are different from those underlying action potential-driven synchronized transmitter release. Differential neuromodulation of these two distinct release modes by metabotropic glutamate receptors (mGluRs) constitutes critical supporting evidence. However, the mechanisms underlying such a differential modulation are not understood. Here, we investigated the mechanisms of the modulation by group I mGluRs (mGluR Is) on spontaneous glutamate release in the medial nucleus of the trapezoid body (MNTB), an auditory brainstem nucleus critically involved in sound localization. Whole-cell patch recordings from brainstem slices of mice of both sexes were performed. Activation of mGluR I by 3,5-dihydroxyphenylglycine (3,5-DHPG; 200 µm) produced an inward current at -60 mV and increased spontaneous glutamate release in MNTB neurons. Pharmacological evidence indicated involvement of both mGluR1 and mGluR5, which was further supported for mGluR5 by immunolabeling results. The modulation was eliminated by blocking NaV channels (tetrodotoxin, 1 µm), persistent Na+ current (INaP; riluzole, 10 µm), or CaV channels (CdCl2, 100 µm). Presynaptic calyx recordings revealed that 3,5-DHPG shifted the activation of INaP to more hyperpolarized voltages and increased INaP at resting membrane potential. Our data indicate that mGluR I enhances spontaneous glutamate release via regulation of INaP and subsequent Ca2+-dependent processes under resting condition.SIGNIFICANCE STATEMENT For brain cells to communicate with each other, neurons release chemical messengers, termed neurotransmitters, in response to action potential invasion (evoked release). Neurons also release neurotransmitters spontaneously. Recent work has revealed different release machineries underlying these two release modes, and their different roles in synaptic development and plasticity. Our recent work discovered differential neuromodulation of these two release modes, but the mechanisms are not well understood. The present study showed that activation of group I metabotropic glutamate receptors enhanced spontaneous glutamate release in an auditory brainstem nucleus, while suppressing evoked release. The modulation is dependent on a persistent Na+ current and involves subsequent Ca2+ signaling, providing insight into the mechanisms underlying the different release modes in auditory processing.


Asunto(s)
Ácido Glutámico/metabolismo , Receptores de Glutamato Metabotrópico/metabolismo , Sinapsis/metabolismo , Cuerpo Trapezoide/metabolismo , Animales , Agonistas de Aminoácidos Excitadores/farmacología , Potenciales Postsinápticos Excitadores , Femenino , Glicina/análogos & derivados , Glicina/farmacología , Masculino , Ratones , Ratones Endogámicos C57BL , Receptores de Glutamato Metabotrópico/agonistas , Resorcinoles/farmacología , Bloqueadores de los Canales de Sodio/farmacología , Localización de Sonidos , Sinapsis/efectos de los fármacos , Sinapsis/fisiología , Tetrodotoxina/farmacología , Cuerpo Trapezoide/citología , Cuerpo Trapezoide/fisiología
19.
Anal Chem ; 93(14): 5684-5690, 2021 04 13.
Artículo en Inglés | MEDLINE | ID: mdl-33797237

RESUMEN

Liquid chromatography tandem mass spectrometry (LC/MS) and other mass spectrometric technologies have been widely applied for triacylglycerol profiling. One challenge for targeted identification of fatty acyl moieties that constitute triacylglycerol species in biological samples is the numerous combinations of 3 fatty acyl groups that can form a triacylglycerol molecule. Manual determination of triacylglycerol structures based on peak intensities and retention time can be highly inefficient and error-prone. To resolve this, we have developed TAILOR-MS, a Python (programming language) package that aims at assisting: (1) the generation of targeted LC/MS methods for triacylglycerol detection and (2) automating triacylglycerol structural determination and prediction. To assess the performance of TAILOR-MS, we conducted LC/MS triacylglycerol profiling of bovine milk and two infant formulas. Our results confirmed dissimilarities between bovine milk and infant formula triacylglycerol composition. Furthermore, we identified 247 triacylglycerol species and predicted the possible existence of another 317 in the bovine milk sample, representing one of the most comprehensive reports on the triacylglycerol composition of bovine milk thus far. Likewise, we presented here a complete infant formula triacylglycerol profile and reported >200 triacylglycerol species. TAILOR-MS dramatically shortened the time required for triacylglycerol structural identification from hours to seconds and performed decent structural predictions in the absence of some triacylglycerol constituent peaks. Taken together, TAILOR-MS is a valuable tool that can greatly save time and improve accuracy for targeted LC/MS triacylglycerol profiling.


Asunto(s)
Fórmulas Infantiles , Leche , Animales , Bovinos , Humanos , Lactante , Espectrometría de Masas , Leche Humana , Triglicéridos
20.
Opt Express ; 29(23): 37835-37844, 2021 Nov 08.
Artículo en Inglés | MEDLINE | ID: mdl-34808848

RESUMEN

In this study, deep ultraviolet light-emitting diodes (DUV-LEDs) with a reflective passivation layer (RPL) were investigated. The RPL consists of HfO2/SiO2 stacks as distributed Bragg reflectors, which are deposited on two DUV-LEDs with different p-GaN thicknesses. The RPL structure improved the external quantum efficiency droops of the DUV-LEDs with thick and thin p-GaN, thereby increasing their light output power by 18.4% and 39.4% under injection current of 500 mA and by 17.9% and 37.9% under injection current of 1000 mA, respectively. The efficiency droops of the DUV-LEDs with and without the RPL with thick p-GaN were 20.1% and 19.1% and with thin p-GaN were 18.0% and 15.6%, respectively. The DUV-LEDs with the RPL presented improved performance. The above results demonstrate the potential for development of the RPLs for DUV-LED applications.

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