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1.
Genomics ; 116(5): 110881, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38906513

RESUMO

Alkaloids are the main medicinal components in Houttuynia cordata. In this study, two accessions 6# and 7# of H. cordata underwent thorough metabolomic analyses to identify and quantify alkaloid phytometabolites. It turned out that the alkaloid types were largely similar between 6# and 7#, and the identified 81 alkaloids could be divided into nine structural classes. However, the content of alkaloids in the two accessions was quite different. According to transcriptome data, a total of 114 differentially expressed genes related to alkaloid metabolism were screened. The alkaloid synthesis pathway of the two varieties was mainly different in the isoquinoline alkaloid biosynthesis and indole alkaloid biosynthesis; four genes A22110063c_transcript_59323, A22110063c_transcript_60118, A22110063c_transcript_51672 and A22110063c_transcript_48784 were highly expressed in 7#, which could be key candidate genes of alkaloid metabolism and warrant further analysis. These results provide a reference for the medicinal application of H. cordata and breeding alkaloid rich varieties.

2.
Nanotechnology ; 35(22)2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38387089

RESUMO

Low-cost, small-sized, and easy integrated high-performance photodetectors for photonics are still the bottleneck of photonic integrated circuits applications and have attracted increasing attention. The tunable narrow bandgap of two-dimensional (2D) layered molybdenum ditelluride (MoTe2) from ∼0.83 to ∼1.1 eV makes it one of the ideal candidates for near-infrared (NIR) photodetectors. Herein, we demonstrate an excellent waveguide-integrated NIR photodetector by transferring mechanically exfoliated 2D MoTe2onto a silicon nitride (Si3N4) waveguide. The photoconductive photodetector exhibits excellent responsivity (R), detectivity (D*), and external quantum efficiency at 1550 nm and 50 mV, which are 41.9 A W-1, 16.2 × 1010Jones, and 3360%, respectively. These optoelectronic performances are 10.2 times higher than those of the free-space device, revealing that the photoresponse of photodetectors can be enhanced due to the presence of waveguide. Moreover, the photodetector also exhibits competitive performances over a broad wavelength range from 800 to 1000 nm with a highRof 15.4 A W-1and a largeD* of 59.6 × 109Jones. Overall, these results provide an alternative and prospective strategy for high-performance on-chip broadband NIR photodetectors.

3.
Arch Toxicol ; 98(6): 1827-1842, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38563869

RESUMO

Aminoglycosides are commonly used antibiotics for treatment of gram-negative bacterial infections, however, they might act on inner ear, leading to hair-cell death and hearing loss. Currently, there is no targeted therapy for aminoglycoside ototoxicity, since the underlying mechanisms of aminoglycoside-induced hearing impairments are not fully defined. This study aimed to investigate whether the calcium channel blocker verapamil and changes in intracellular & extracellular calcium could ameliorate aminoglycoside-induced ototoxicity in zebrafish. The present findings showed that a significant decreased number of neuromasts in the lateral lines of zebrafish larvae at 5 days' post fertilization after neomycin (20 µM) and gentamicin (20 mg/mL) exposure, which was prevented by verapamil. Moreover, verapamil (10-100 µM) attenuated aminoglycoside-induced toxic response in different external calcium concentrations (33-3300 µM). The increasing extracellular calcium reduced hair cell loss from aminoglycoside exposure, while lower calcium facilitated hair cell death. In contrast, calcium channel activator Bay K8644 (20 µM) enhanced aminoglycoside-induced ototoxicity and reversed the protective action of higher external calcium on hair cell loss. However, neomycin-elicited hair cell death was not altered by caffeine, ryanodine receptor (RyR) agonist, and RyR antagonists, including thapsigargin, ryanodine, and ruthenium red. The uptake of neomycin into hair cells was attenuated by verapamil and under high external calcium concentration. Consistently, the production of reactive oxygen species (ROS) in neuromasts exposed to neomycin was also reduced by verapamil and high external calcium. Significantly, zebrafish larvae when exposed to neomycin exhibited decreased swimming distances in reaction to droplet stimulus when compared to the control group. Verapamil and elevated external calcium effectively protected the impaired swimming ability of zebrafish larvae induced by neomycin. These data imply that prevention of hair cell damage correlated with swimming behavior against aminoglycoside ototoxicity by verapamil and higher external calcium might be associated with inhibition of excessive ROS production and aminoglycoside uptake through cation channels. These findings indicate that calcium channel blocker and higher external calcium could be applied to protect aminoglycoside-induced listening impairments.


Assuntos
Antibacterianos , Bloqueadores dos Canais de Cálcio , Cálcio , Gentamicinas , Células Ciliadas Auditivas , Neomicina , Verapamil , Peixe-Zebra , Animais , Bloqueadores dos Canais de Cálcio/farmacologia , Cálcio/metabolismo , Verapamil/farmacologia , Neomicina/toxicidade , Células Ciliadas Auditivas/efeitos dos fármacos , Células Ciliadas Auditivas/metabolismo , Gentamicinas/toxicidade , Antibacterianos/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Ototoxicidade/prevenção & controle , Aminoglicosídeos/toxicidade , Sistema da Linha Lateral/efeitos dos fármacos , Larva/efeitos dos fármacos , Perda Auditiva/induzido quimicamente , Perda Auditiva/prevenção & controle
4.
Addict Biol ; 28(12): e13351, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38017646

RESUMO

Conditioned place preference (CPP) paradigm in zebrafish has been used to measure drug reward, but there is limited research on CPP reinstatement to determine relapse vulnerability. The present study aimed to investigate extinction and reinstatement of methamphetamine (MA)-induced CPP in zebrafish and evaluate the model's predictive validity. Zebrafish received different doses of MA (0-60 mg/kg) during CPP training. The preferred dose of MA at 40 mg/kg was used for extinction via either confined or nonconfined procedures. The extinguished CPP was reinstated by administering a priming dose of MA (20 mg/kg) or various stressors. To assess persistent susceptibility to reinstatement, MA CPP and reinstatement were retested following 14 days of abstinence. In addition, the effects of SCH23390, naltrexone, and clonidine on MA CPP during acquisition, expression, or reinstatement phases were monitored. MA induced CPP in a dose-dependent manner. Both nonconfined and confined extinction procedures time-dependently reduced the time spent on the MA-paired side. A priming dose of MA, chasing stress, or yohimbine reinstated the extinguished CPP. After 14 days of abstinence, the MA CPP remained extinguished and was significantly reinstated by MA priming or chasing stress. Similar to the observations in rodents, SCH23390 suppressed the acquisition of MA CPP, naltrexone reduced the expression and MA priming-induced reinstatement, while clonidine prevented stress-induced reinstatement of MA CPP. This work expanded the zebrafish CPP paradigm to include extinction and reinstatement phases, demonstrating predictive validity and highlighting its potential as a valuable tool for exploring drug relapse.


Assuntos
Metanfetamina , Animais , Metanfetamina/farmacologia , Peixe-Zebra , Morfina/farmacologia , Extinção Psicológica , Clonidina/farmacologia , Naltrexona/farmacologia , Recidiva
5.
BMC Ophthalmol ; 23(1): 133, 2023 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-37013529

RESUMO

BACKGROUND: Cortisol plays a role in the pathogenesis of central serous chorioretinopathy (CSC). CSC patients have abnormal time-dependent changes in cortisol levels. Here we report a rare case of a patient with central serous chorioretinopathy whose pigment epithelial detachment (PED) exhibited time-dependent recurrence and resolution. CASE PRESENTATION: A 47-year-old man presented in 2016 for vision loss in the left eye related to recurrent CSC. During follow-up, his PED was observed to resolve spontaneously while he was still in our clinic and recurred the next morning. Such time-dependent changes of the PED were observed in several next follow-ups without any intervention. After excluding possible external factors, the abnormal diurnal variation of cortisol was considered as the internal factor affecting PED. CONCLUSIONS: This is the first article that described the spontaneous time-dependent recurrence and resolution of PED without external interference, where endogenous cortisol may be responsible. Interventions against the abnormal cortisol level might be a potential treatment strategy for CSC. More research is urged to explore the impact of the diurnal change in cortisol levels on eyes with CSC.


Assuntos
Coriorretinopatia Serosa Central , Descolamento Retiniano , Masculino , Humanos , Pessoa de Meia-Idade , Coriorretinopatia Serosa Central/complicações , Coriorretinopatia Serosa Central/diagnóstico , Hidrocortisona , Descolamento Retiniano/etiologia , Descolamento Retiniano/complicações , Epitélio Pigmentado da Retina/patologia , Tomografia de Coerência Óptica , Angiofluoresceinografia , Estudos Retrospectivos
6.
Opt Express ; 30(9): 15201-15210, 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35473247

RESUMO

Dispersive time stretch has made many ultrafast applications possible owing to its high frame rate, as compared to conventional spectroscopies. By further introducing a converging time lens, this spectroscopy can resolve arbitrary emission spectra within the aperture. However, a spectral resolution of tens of picometers hinders its high-precision application. There are two limitations: the temporal aperture of the acquired signal and the actual acquisition bandwidth. To overcome these restrictions, two approaches were developed. First, a large-aperture time lens, with higher-order dispersion compensation, is used to overcome the fundamental limit of the time-bandwidth product. Second, asynchronous optical sampling, based on two frequency combs, overcomes the technical limit of the acquisition bandwidth. As a result, in this study, time-stretch spectroscopy achieved a 1-pm spectral resolution, 24-nm observation bandwidth, and 1-kHz frame rate. Moreover, it was used to observe some spectral dynamics of the random lasing process and devices with narrow spectral widths. This scheme provides essential improvement for time-stretch spectroscopy to achieve high precision.

7.
Opt Express ; 30(18): 32650-32659, 2022 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-36242321

RESUMO

All-optical canonical logic unit (CLU) is the basic building block of high-speed optical logic operation and complex optical computing. By utilizing the parallelism of optical signals, multichannel multicasting of all-optical CLUs can expand the capacity of the computing system effectively. Here, we propose and experimentally demonstrate the 40 Gb/s all-optical reconfigurable two-input CLUs generated in seven wavelength channels via four-wave mixing (FWM) in the nonlinearity-enhanced silicon waveguide. By introducing reverse-biased PIN junctions to reduce nonlinear loss, the output power of converted light can be increased over 10 dB. Moreover, pumped by two optical signals and a continuous wave beam, a full set of reconfigurable CLUs is multicasted in seven parallel wavelength channels. All logic signals with error-free performance are realized. Attributing to the rate transparency of FWM and parallel multicasting of logic functions, the proposed scheme offers more flexibility and expandability in future high-speed optical logic processing and complex optical computing.

8.
Sensors (Basel) ; 22(23)2022 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-36501818

RESUMO

Water molecules play a very important role in the hydration and dehydration process of hydrates, which may lead to distinct physical and chemical properties, affecting their availability in practical applications. However, miniaturized, integrated sensors capable of the rapid, sensitive sensing of water molecules in the hydrate are still lacking, limiting their proliferation. Here, we realize the high-sensitivity sensing of water molecules in copper sulfate pentahydrate (CuSO4·5H2O), based on an on-chip terahertz whispering gallery mode resonator (THz-WGMR) fabricated on silicon material via CMOS-compatible technologies. An integrated THz-WGMR with a high-Q factor of 3305 and a resonance frequency of 410.497 GHz was proposed and fabricated. Then, the sensor was employed to distinguish the CuSO4·xH2O (x = 5, 3, 1). The static characterization from the CuSO4·5H2O to the copper sulfate trihydrate (CuSO4·3H2O) experienced blueshifts of 0.55 GHz/µmol, whereas the dehydration process of CuSO4·3H2O to copper sulfate monohydrate (CuSO4·H2O) exhibited blueshifts of 0.21 GHz/µmol. Finally, the dynamic dehydration processes of CuSO4·5H2O to CuSO4·3H2O at different temperatures were monitored. We believe that our proposed THz-WGMR sensors with highly sensitive substance identification capabilities can provide a versatile and integrated platform for studying the transformation between substances, contributing to hydrated/crystal water-assisted biochemical applications.


Assuntos
Sulfato de Cobre , Silício , Água
9.
Anal Chem ; 93(16): 6456-6462, 2021 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-33861566

RESUMO

Rapid point-of-care (POC) quantification of low virus RNA load would significantly reduce the turn-around time for the PCR test and help contain a fast-spreading epidemic. Herein, we report a droplet digital PCR (ddPCR) platform that can achieve this sensitivity and rapidity without bulky lab-bound equipment. The key technology is a flattened pipette tip with an elliptical cross-section, which extends a high aspect-ratio microfluidic chip design to pipette scale, for rapid (<5 min) generation of several thousand monodispersed droplets ∼150 to 350 µm in size with a CV of ∼2.3%. A block copolymer surfactant (polyoxyalkylene F127) is used to stabilize these large droplets in oil during thermal cycling. At this droplet size and number, positive droplets can be counted by eye or imaged by a smartphone with appropriate illumination/filtering to accurately quantify up to 100 target copies. We demonstrate with 2019 nCoV-PCR assay LODs of 3.8 copies per 20 µL of sample and a dynamic range of 4-100 copies. The ddPCR platform is shown to be inhibitor resistant with spiked saliva samples, suggesting RNA extraction may not be necessary. It represents a rapid 1.5-h POC quantitative PCR test that requires just a pipette equipped with elliptical pipette tip, a commercial portable thermal cycler, a smartphone, and a portable trans-illuminator, without bulky and expensive micropumps and optical detectors that prevent POC application.


Assuntos
COVID-19 , Sistemas Automatizados de Assistência Junto ao Leito , Humanos , Reação em Cadeia da Polimerase em Tempo Real , SARS-CoV-2 , Carga Viral
10.
Opt Express ; 29(2): 2153-2161, 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33726416

RESUMO

The radio frequency (RF) spectrum of microcombs can be used to evaluate its phase noise features and coherence between microcomb teeth. Since microcombs possess characteristics such as high repetition rate, narrow linewidth and ultrafast dynamical evolution, there exists strict requirement on the bandwidth, resolution and frame rate of RF measurement system. In this work, a scheme with 1.8-THz bandwidth, 7.5-MHz spectral resolution, and 100-Hz frame rate is presented for RF spectrum measurement of microcombs by using an all-optical RF spectrum analyzer based on cross-phase modulation and Fabry Perot (FP) spectrometer, namely FP-assisted light intensity spectrum analyzer (FP-assisted LISA). However, extra dispersion introduced by amplifying the microcombs will deteriorate the bandwidth performance of measured RF spectrum. After compensating the extra dispersion through monitoring the dispersion curves measured by FP-assisted LISA, the more precise RF spectra of microcombs are measured. Then, the system is used to measure the noise sidebands and line shape evolution of microcombs within 2s temporal window, in which dynamic RF combs variation at different harmonic frequencies up to 1.96 THz in modulation instability (MI) state and soliton state are recorded firstly. Therefore, the improved bandwidth and resolution of FP-assisted LISA enable more precise measurement of RF spectrum, paving a reliable way for researches on physical mechanism of microcombs.

11.
Anticancer Drugs ; 32(2): 127-137, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33417325

RESUMO

Gastric cancer is one of the most common malignant tumors. MicroRNA-196b (miR-196b) has been demonstrated to play important roles in human cancers. However, its functions in gastric cancer progression were still largely unknown. In this study, the expression of miR-196b was determined by quantitative real-time PCR. Esophageal cancer-related gene 4 (ECRG4) level was examined by western blot assay and immunohistochemistry staining assay. Cell proliferation was evaluated by Cell Counting Kit-8 (CCK-8) assay and colony formation assay. Cell migration and invasion were analyzed by transwell assay. The association between miR-196b and ECRG4 was analyzed by dual-luciferase reporter assay. The functional role of miR-196b in vivo was analyzed by murine xenograft assay. As a result, we found the expression of miR-196b was elevated and the protein expression of ECRG4 was reduced in gastric cancer tissues and cells. MiR-196b inhibition suppressed gastric cancer cell proliferation, migration and invasion. ECRG4 was a target of miR-196b and its protein expression was negatively regulated by miR-196b. Moreover, ECRG4 overexpression showed similar effects with miR-196b inhibition on the malignant behaviors of GC cells and ECRG4 knockdown reversed the effects of miR-196b inhibition on gastric cancer cell proliferation, migration and invasion. In addition, miR-196b inhibition suppressed tumor volume and weight in vivo. In conclusion, downregulation of miR-196b inhibited gastric cancer progression by modulating ECRG4 expression, indicating that miR-196b might be a potential therapeutic target for gastric cancer.


Assuntos
MicroRNAs/biossíntese , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Proteínas Supressoras de Tumor/biossíntese , Idoso , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação para Baixo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Regulação para Cima
12.
J Chem Inf Model ; 61(11): 5614-5625, 2021 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-34664967

RESUMO

Pyruvate metabolism requires the mitochondrial pyruvate carrier (MPC) proteins to transport pyruvate from the intermembrane space through the inner mitochondrial membrane to the mitochondrial matrix. The lack of the atomic structures of MPC hampers the understanding of the functional states of MPC and molecular interactions with the substrate or inhibitor. Here, we develop the de novo models of human MPC complexes and characterize the conformational dynamics of the MPC heterodimer formed by MPC1 and MPC2 (MPC1/2) by computational simulations. Our results reveal that functional MPC1/2 prefers to adopt an inward-open conformation, with the carrier open to the matrix side, whereas the outward-open states are less populated. The energy barrier for pyruvate transport in MPC1/2 is low enough, and the inhibitor UK5099 blocks the pyruvate transport by stably binding to MPC1/2. Notably, consistent with experimental results, the MPC1 L79H mutation significantly alters the conformations of MPC1/2 and thus fails for substrate transport. However, the MPC1 R97W mutation seems to retain the transport activity. The present de novo models of MPC complexes provide structural insights into the conformational states of MPC complexes and mechanistic understanding of interactions between the substrate/inhibitor and MPC proteins.


Assuntos
Proteínas de Transporte da Membrana Mitocondrial/química , Transportadores de Ácidos Monocarboxílicos , Humanos , Mitocôndrias , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Membranas Mitocondriais/metabolismo , Proteínas Mitocondriais/metabolismo , Ácido Pirúvico
13.
BMC Pregnancy Childbirth ; 21(1): 259, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33771120

RESUMO

BACKGROUND: Computed tomography (CT) is the preferred imaging technique for the evaluation of COVID-19 pneumonia. However, it is not suitable as a monitoring tool for pregnant women because of the risk of ionizing radiation damage to the fetus as well as the possible infection of others. In this study, we explored the value of bedside lung ultrasound (LUS) as an alternative to CT for the detection and monitoring of lung involvement in pregnant women with COVID-19. METHODS: Clinical and LUS data of 39 pregnant women with COVID-19 were retrospectively reviewed. All LUS and CT images were analyzed to summarize the findings and calculate LUS scores and CT scores for each patient. LUS findings were compared with CT, and correlation between LUS scores and CT scores was evaluated. RESULTS: Among the 39 pregnant women, there were 6 mild-type cases, 29 common-type cases, 4 severe-type cases, and no critical-type cases. The most common LUS findings of COVID-19 pneumonia in pregnant women were various grades of multiple B-lines (84.6%), thickened and irregular pleural lines (71.8%), pleural effusion (61.5%) and small multifocal consolidation limited to the subpleural space (35.9%). The mean LUS score at admission was 0 points in mild-type cases, 10.6 points in common-type cases and 15.3 points in severe-type cases (P < 0.01). The correlation between LUS scores and CT was 0.793. All patients were clinically cured and each underwent an average of three LUS follow-ups during hospitalization. The mean LUS score at discharge was 5.6 points lower than that at admission. The consistency of LUS and chest CT during follow-up was 0.652. CONCLUSIONS: Quantitative LUS scoring can effectively instead of CT for detecting and monitoring of COVID-19 pneumonia in pregnant women and protect fetuses from the risk of ionizing radiation.


Assuntos
COVID-19/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Complicações Infecciosas na Gravidez/diagnóstico por imagem , Ultrassonografia/métodos , Adulto , Feminino , Hospitalização , Humanos , Gravidez , Estudos Retrospectivos , SARS-CoV-2 , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X , Adulto Jovem
14.
J Ultrasound Med ; 40(11): 2477-2486, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33470432

RESUMO

OBJECTIVES: To evaluate the value of time-intensity curve (TIC) analysis of contrast-enhanced ultrasound (CEUS) signal to differentiate malignant from benign orbital space-occupying lesions. METHODS: The CEUS signal of 111 patients with orbital space-occupying lesions was retrospectively analyzed using SonoLiver software. TIC-related parameters such as the arrival time (AT), rise time (RT), time to peak (TTP), maximum intensity (IMAX), mean transit time (mTT), slope of the increase (RS), and slope of the decrease (DS) were compared between the malignant and benign groups. Receiver operating characteristic (ROC) curve analysis was used to acquire the cutoff values of these parameters for differential diagnosis. RESULTS: TIC patterns were characterized by fast increase and fast decrease in signal intensity in the malignant group, fast increase and a slow decrease in signal intensity in the benign group. The differences in the IMAX, RS, DS, mTT, TTP, and RT between the 2 groups were statistically significant (p <.01), while the difference in the AT were not (p = .672). ROC curve analysis showed that IMAX = 427.20, DS = 34.72, and mTT = 33.55 were the best cutoff values for differential diagnosis of malignant and benign space-occupying lesions. The accuracy rate of CEUS visual evaluation for differential diagnosis was 66.67% (74/111), while TIC quantitative analysis could effectively improve the accuracy to 89.19% (99/111). CONCLUSIONS: TIC analysis can improve CEUS efficiency to differentiate malignant from benign orbital space-occupying lesions.


Assuntos
Meios de Contraste , Diagnóstico Diferencial , Humanos , Curva ROC , Estudos Retrospectivos , Ultrassonografia
15.
J Ultrasound Med ; 40(9): 1787-1794, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33174632

RESUMO

OBJECTIVES: Coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic, raising widespread public health concerns. Our team treated hospitalized patients with COVID-19 in Wuhan, where the outbreak first began, and we suspected that SARS-CoV-2 may cause testicular infection in male patients. We conducted this study to explore that observation. METHODS: We enrolled male patients with a confirmed diagnosis of COVID-19 and performed a bedside ultrasound (US) examination of the scrotum, focused on findings of acute inflammation such as tunica albuginea thickening, enlargement and heterogeneous echogenicity of the testis, epididymis, or both, an abscess, scrotal wall edema, and hydrocele. Then we compared the proportions of observed epididymo-orchitis in patients from different age groups and COVID-19 severity groups. RESULTS: A total of 142 patients with COVID-19 were enrolled in our study, and 32 (22.5%) patients had acute orchitis, epididymitis, or epididymo-orchitis on scrotal US imaging, according to the diagnosis criteria. The observed risk of acute scrotal infection increased with age, with the incidence reaching 53.3% in men older than 80 years. We also observed that men with severe COVID-19 had a significantly higher possibility of epididymo-orchitis compared to the nonsevere COVID-19 group (P = .037). CONCLUSIONS: This study shows US imaging evidence that SARS-CoV-2 may cause infection of the testis or epididymis, and the risk is worthy of the attention of clinicians.


Assuntos
COVID-19 , Orquite , Idoso de 80 Anos ou mais , China/epidemiologia , Humanos , Masculino , Orquite/diagnóstico por imagem , Orquite/epidemiologia , SARS-CoV-2 , Ultrassonografia
16.
J Chem Inf Model ; 60(8): 3958-3968, 2020 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-32649824

RESUMO

Dopamine (DA) transporter (DAT) is a major target for psychostimulant drugs of abuse such as cocaine that competitively binds to DAT, inhibits DA reuptake, and consequently increases synaptic DA levels. In addition to the central binding site inside DAT, the available experimental evidence suggests the existence of alternative binding sites on DAT, but detection and characterization of these sites are challenging by experiments alone. Here, we integrate multiple computational approaches to probe the potential binding sites on the wild-type Drosophila melanogaster DAT and identify a new allosteric site that displays high affinity for cocaine. This site is located on the surface of DAT, and binding of cocaine is primarily dominated by interactions with hydrophobic residues surrounding the site. We show that cocaine binding to this new site allosterically reduces the binding of DA/cocaine to the central binding pocket, and simultaneous binding of two cocaine molecules to a single DAT seems infeasible. Furthermore, we find that binding of cocaine to this site stabilizes the conformation of DAT but alters the conformational population and thereby reduces the accessibility by DA, providing molecular insights into the inhibitory mechanism of cocaine. In addition, our results indicate that the conformations induced by cocaine binding to this site may be relevant to the oligomerization of DAT, highlighting a potential role of this new site in modulating the function of DAT.


Assuntos
Cocaína , Proteínas da Membrana Plasmática de Transporte de Dopamina/química , Proteínas de Drosophila/química , Drosophila melanogaster/química , Sítio Alostérico , Animais , Sítios de Ligação
17.
Sensors (Basel) ; 21(1)2020 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-33396367

RESUMO

Cooperative multipoint transmission (CoMP) is one of the most promising paradigms for mitigating interference in cloud radio access networks (C-RAN). It allows multiple remote radio units (RRUs) to transmit the same data flow to a user to further improve the signal quality. However, CoMP may incur redundant data transmission over fronthaul network in the C-RAN. In a C-RAN employing CoMP, a key problem is how to coordinate heterogeneous resource allocation to maximize the cooperation gain while reducing the fronthaul load. In this paper, the cooperation transmission based on a multi-dimensional resource schedule (MRSCT) scheme, jointly considering user association, spectrum resource allocation, and wavelength resource allocation, is firstly envisioned in the underlying C-RAN integrating time and wavelength division multiplexing passive optical network (TWDM-PON) to maximize fronthaul efficiency. Then a two-timescale resource allocation framework including two sub-approaches is established. More specially, the first sub-approach mainly focuses on exploiting reinforcement learning to obtain a wavelength resource allocation strategy to relieve fronthaul traffic load. Moreover, the second sub-approach adopts the overlapping coalition formation game to establish a user-centric cooperative set, where spectrum resources are dynamically allocated to further alleviate the interference issue. The theoretical analysis and simulation results validate the performance of MRSCT scheme on the fronthaul efficiency, user experience, and system service capability.

18.
Biochem Biophys Res Commun ; 511(3): 573-578, 2019 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-30824189

RESUMO

The ubiquitous glucose transporter 1 (GLUT1) is physiologically and pathologically relevant in energy metabolism of the CNS, skeletal muscles, cancer cells etc. Extensive experiments on GLUT1 produced thorough understandings of its expressions, functions, and structures which were recently resolved to atomic accuracy. However, theoretical understandings are still controversial about how GLUT1 facilitates glucose diffusion across the cell membrane. Molecular dynamics (MD) simulations of the current literature have GLUT1 embedded in a symmetric bilayer of a single lipid type. They provide atomistic illustrations of the alternating access theory (AAT), but the simulation results are inconsistent with the undisputed experimental data of kinetics showing rapid transport of glucose at near-physiological temperatures, high Arrhenius activation barrier in zero-trans uptake, and large trans-acceleration at sub-physiological temperatures. In this research, we embedded GLUT1 in an asymmetric bilayer of multiple lipids to better mimic the erythrocyte membrane. We ran unbiased MD simulations at 37 °C and at 5 °C and found a new mechanism of glucose transport via GLUT1: The extracellular (EC) gate opened wide for EC glucopyranose at 37 °C and, only in the presence of intracellular (IC) glucose, at 5 °C. In the absence of IC glucose at 5 °C, the EC gate opened narrowly for acyclic glucose, gating out glucopyranose. This EC-gating mechanism is simpler than AAT and yet it well explains for the rapid glucose transport at near-physiological temperatures and large trans-acceleration at sub-physiological temperatures. It also explains why zero-trans uptake (involving the pyranose-to-aldehyde transformation) has an Arrhenius barrier ∼20 kcal/mol higher than the equilibrium exchange transport.


Assuntos
Transportador de Glucose Tipo 1/metabolismo , Glucose/metabolismo , Transporte Biológico Ativo , Difusão , Eritrócitos/metabolismo , Humanos , Cinética , Bicamadas Lipídicas/metabolismo , Simulação de Acoplamento Molecular , Temperatura
19.
Opt Express ; 27(21): 30441-30448, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31684291

RESUMO

Parametric spectro-temporal analyzer (PASTA) has been demonstrated as a powerful tool for ultrafast spectrum measurement with superior frame rate and resolution. Compared with other time-stretch-based counterparts, the temporal focusing mechanism enlarges the initial condition and enables the observation of arbitrary waveform, especially the emission spectrum. However, due to the limited conversion bandwidth of the parametric mixing-based time-lens, the observation bandwidth of PASTA is constrained within the C (conventional) band, which hinders its practical applications. To overcome this constraint, both stokes and anti-stokes conversions of the parametric mixing process are leveraged, and the concept of time division multiplexing (TDM) is introduced to ensure their separability. Therefore, the TDM-based PASTA system successfully demultiplexes the C band and L (long) band spectra in two adjacent temporal frames. It is capable of reconstructing the wavelength-to-time sequence for arbitrary waveform over a record 58-nm observation bandwidth, which can be further improved by optimizing the filters and amplifiers. Meanwhile, both of these two bands achieve 20-pm resolution, 10-MHz frame rate, and -30-dBm sensitivity. Moreover, this TDM concept can also be applied to other parametric mixing-based temporal imaging systems to enlarge the working wavelength band, such as temporal magnification.

20.
Opt Express ; 27(3): 2621-2631, 2019 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-30732297

RESUMO

An inertial-free, ultrafast frequency comb source based on two chirped optical frequency combs (OFCs) is proposed and experimentally demonstrated. The high linearity frequency sweeping is realized by the Vernier effect between the two OFCs rather than any mechanical motion component, so that good stability and reliability are ensured and no recalibration or resampling process is required. Swept rate up to 1 MHz is realized while keeping a narrow instantaneous linewidth of 0.03 nm, thanks to the extra-cavity frequency sweeping method. The wavelength step is proportional to the swept rate (3.8 pm at 10 kHz), and can be tuned by changing the repetition rate difference between the two OFCs. This swept source is applied for high-speed wavelength encoded imaging and achieves 4.4-µm spatial resolution at a 329-kHz frame rate. Compared with the traditional time-stretch microscopy, the signal acquisition bandwidth decreased from 3.8 GHz to below 90 MHz to achieve the same spatial resolution. Furthermore, the exposure time for a specific wavelength is much longer due to the discrete sweeping feature, which is a benefit for higher sensitivity. This discrete swept source provided a promising low-cost option for high-speed biomedical imaging systems and high-accuracy spectroscopy.

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