Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 551
Filtrar
1.
J Transl Med ; 22(1): 883, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39354613

RESUMO

Single-cell technology depicts integrated tumor profiles including both tumor cells and tumor microenvironments, which theoretically enables more robust diagnosis than traditional diagnostic standards based on only pathology. However, the inherent challenges of single-cell RNA sequencing (scRNA-seq) data, such as high dimensionality, low signal-to-noise ratio (SNR), sparse and non-Euclidean nature, pose significant obstacles for traditional diagnostic approaches. The diagnostic value of single-cell technology has been largely unexplored despite the potential advantages. Here, we present a graph neural network-based framework tailored for molecular diagnosis of primary liver tumors using scRNA-seq data. Our approach capitalizes on the biological plausibility inherent in the intercellular communication networks within tumor samples. By integrating pathway activation features within cell clusters and modeling unidirectional inter-cellular communication, we achieve robust discrimination between malignant tumors (including hepatocellular carcinoma, HCC, and intrahepatic cholangiocarcinoma, iCCA) and benign tumors (focal nodular hyperplasia, FNH) by scRNA data of all tissue cells and immunocytes only. The efficacy to distinguish iCCA from HCC was further validated on public datasets. Through extending the application of high-throughput scRNA-seq data into diagnosis approaches focusing on integrated tumor microenvironment profiles rather than a few tumor markers, this framework also sheds light on minimal-invasive diagnostic methods based on migrating/circulating immunocytes.


Assuntos
Neoplasias Hepáticas , Redes Neurais de Computação , Análise de Célula Única , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Análise de Célula Única/métodos , RNA/metabolismo , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Análise de Sequência de RNA
2.
Anal Chem ; 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39382097

RESUMO

Lysosomes are multifunctional organelles vital for cellular homeostasis with distinct subpopulations characterized by varying levels of Cl-, Ca2+, and H+. In situ visualization of these parameters is crucial for lysosomal research, yet developing probes that can simultaneously detect multiple ions remains challenging. Herein, we developed a lysosome-targeting ternary recognition ratiometric fluorescent probe based on tetrahedral DNA nanostructures (TDNs) to analyze lysosome subpopulations by Cl-, Ca2+, and pH. The TDN probe is assembled from four single-stranded DNAs, each end-modified with responsive fluorophores (Pr-Cl for Cl-, Pr-Ca for Ca2+, and Pr-pH for pH) or a reference fluorophore (Cy5). The fluorophores are integrated at the vertices of the rigid TDN to minimize mutual interference, and their fixed stoichiometry establishes a robust ternary recognition ratiometric fluorescence sensor for in situ resolution of lysosome subpopulations in living cells. Accordingly, a rise in lysosome subpopulations 2/6 characterized by low [Cl-], medium/high [Ca2+], and high pH was observed in the Niemann-Pick disease model cells but seldom observed in the control group. Conversely, there was a marked decline in the fraction of subpopulations 1/4/5 characterized by high [Cl-], medium to low [Ca2+], and pH. These changes were substantially reversed upon treatment. The probe holds great promise for studying lysosome subpopulations and the diagnosis and treatment of related diseases.

3.
Int J Immunopathol Pharmacol ; 38: 3946320241279525, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39180223

RESUMO

OBJECTIVE: This study aims to investigate potential beneficial actions of icariin (ICA) on testicular spermatogenic function in male rats with streptozotocin (STZ)-induced diabetes and to explore the underlying mechanisms. Background: ICA was found to reduce blood glucose, regulate the endocrine function of the reproductive system, and improve testicular spermatogenic function. METHODS: Adult rats were intraperitoneally injected with STZ (65 mg/kg) to induce type 1 diabetes mellitus (T1DM). Diabetic rats were randomly classified intoT1DM (n = 6) and T1DM + ICA (n = 6) groups. Rats without STZ and ICA treatment were assigned as control group (n = 6). The morphology of testicular tissues was examined by histological staining. The mRNA and protein expression levels were determined by quantitative real-time PCR, Western blot and immunostaining, respectively. RESULTS: Rats from T1DM group showed a reduction in epididymis and testis weight, and a decrease in sperm count when compared to control group (p < 0.01), which was attenuated by ICA treatment (p < 0.05) Diabetic rats from T1DM group also exhibited reduced diameter and area of seminiferous tubules, along with decreased spermatogonia and primary spermatocytes number when compared to control group (p < 0.01), which was partially reversed by ICA treatment (p < 0.05) Rats from T1DM group exhibited down-regulation of PCNA mRNA and protein in the testis when compared to control group (p < 0.01); while ICA treatment up-regulated PCNA expression in the testis of diabetic rats compared to T1DM group (p < 0.05). Rats from T1DM group showed up-regulation of Bax and capase-3 and down-regulation of Bcl-2, PKM2, HK2 and lactate dehydrogenase A in the testes when compared to control group (p < 0.05), which was reversed by ICA treatment (p < 0.05). CONCLUSION: These findings suggest that ICA may exert its protective effects on testicular damage in diabetic rats through modulation of glycolysis pathway and suppression of apoptosis.


Assuntos
Diabetes Mellitus Experimental , Flavonoides , Glicólise , Testículo , Animais , Masculino , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/complicações , Testículo/efeitos dos fármacos , Testículo/metabolismo , Testículo/patologia , Glicólise/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Estreptozocina , Espermatogênese/efeitos dos fármacos , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Apoptose/efeitos dos fármacos , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/tratamento farmacológico , Contagem de Espermatozoides
5.
Chem Commun (Camb) ; 60(62): 8087-8090, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-38990605

RESUMO

Lysosomal acidity relies on H+ inflow, which requires counter-ion flows (Cl- and K+) to balance charge. A lysosome targeting ternary recognition fluorescent probe for Cl-, K+, and pH was developed for lysosome acidification counter-ion research. The probe was used to study counter-ion changes when the Cl- channel was blocked and under oxidative pressure.

6.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(3): 324-328, 2024 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-38953255

RESUMO

Objective To assess the influences of self-and interviewer-administered methods on the scores of anxiety and depression questionnaires among the patients with sports injuries.Methods A total of 532 participants with sports injuries treated in the Sports Medicine Center of West China Hospital,Sichuan University from November 2022 to May 2023 were included.They were randomly assigned to either the interviewer-administered group (n=270) or the self-administered group (n=262) to complete the generalized anxiety disorder (GAD-7) and the patient health questionnaire (PHQ-9) scales.The total scores and prevalence rates of anxiety and depression were compared between the two groups.Results There was no statistically significant difference in gender,occupation,or surgical site between the two groups (all P>0.05).The self-administered group had higher scores of GAD-7 and PHQ-9 scales than the interviewer-administered group (P<0.001,P<0.001).A greater proportion of participants in the self-administered group than in the interview-administered group met the criteria for mild to moderate anxiety and depression (P<0.001,P=0.002).The prevalence rates of moderate to severe anxiety (GAD-7≥10) and depression (PHQ-9≥10) showed no statistically significant difference between the two groups (P=0.761,P=0.086).Conclusion This study demonstrates that the participants in the self-administered group are more likely to report mild to moderate symptoms of anxiety and depression than those in the interviewer-administered group.


Assuntos
Ansiedade , Depressão , Humanos , Inquéritos e Questionários , Depressão/epidemiologia , Depressão/diagnóstico , Feminino , Ansiedade/epidemiologia , Masculino , Adulto , Traumatismos em Atletas/psicologia , Traumatismos em Atletas/epidemiologia , China/epidemiologia , Pessoa de Meia-Idade , Adulto Jovem
7.
Acta Pharmacol Sin ; 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926478

RESUMO

Somatostatin receptor 5 (SSTR5) is highly expressed in ACTH-secreting pituitary adenomas and is an important drug target for the treatment of Cushing's disease. Two cyclic SST analog peptides (pasireotide and octreotide) both can activate SSTR5 and SSTR2. Pasireotide is preferential binding to SSTR5 than octreotide, while octreotide is biased to SSTR2 than SSTR5. The lack of selectivity of both pasireotide and octreotide causes side effects, such as hyperglycemia, gastrointestinal disturbance, and abnormal glucose homeostasis. However, little is known about the binding and selectivity mechanisms of pasireotide and octreotide with SSTR5, limiting the development of subtype-selective SST analog drugs specifically targeting SSTR5. Here, we report two cryo-electron microscopy (cryo-EM) structures of SSTR5-Gi complexes activated by pasireotide and octreoitde at resolutions of 3.09 Å and 3.24 Å, respectively. In combination with structural analysis and functional experiments, our results reveal the molecular mechanisms of ligand recognition and receptor activation. We also demonstrate that pasireotide preferentially binds to SSTR5 through the interactions between Tyr(Bzl)/DTrp of pasireotide and SSTR5. Moreover, we find that the Q2.63, N6.55, F7.35 and ECL2 of SSTR2 play a crucial role in octreotide biased binding of SSTR2. Our results will provide structural insights and offer new opportunities for the drug discovery of better selective pharmaceuticals targeting specific SSTR subtypes.

8.
Mar Drugs ; 22(6)2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38921547

RESUMO

Clavatols exhibit a wide range of biological activities due to their diverse structures. A genome mining strategy identified an A5cla cluster from Penicillium sp. MYA5, derived from the Arctic plant Dryas octopetala, is responsible for clavatol biosynthesis. Seven clavatols, including one new clavatol derivate named penicophenone F (1) and six known clavatols (2-7), were isolated from Penicillium sp. MYA5 using a transcriptome mining strategy. These structures were elucidated by comprehensive spectroscopic analysis. Antibacterial, aldose reductase inhibition, and siderophore-producing ability assays were conducted on compounds 1-7. Compounds 1 and 2 demonstrated inhibitory effects on the ALR2 enzyme with inhibition rates of 75.3% and 71.6% at a concentration of 10 µM, respectively. Compound 6 exhibited antibacterial activity against Staphylococcus aureus and Escherichia coli with MIC values of 4.0 µg/mL and 4.0 µg/mL, respectively. Additionally, compounds 1, 5, and 6 also showed potential iron-binding ability.


Assuntos
Antibacterianos , Penicillium , Staphylococcus aureus , Penicillium/genética , Antibacterianos/farmacologia , Antibacterianos/química , Staphylococcus aureus/efeitos dos fármacos , Genômica/métodos , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Testes de Sensibilidade Microbiana , Transcriptoma , Regiões Árticas , Sideróforos/farmacologia , Aldeído Redutase/antagonistas & inibidores , Aldeído Redutase/genética
9.
Am J Transl Res ; 16(5): 1550-1567, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38883343

RESUMO

OBJECT: Amplification of the epidermal growth factor receptor (EGFR) and its active mutant type III (EGFRvIII), frequently occurr in glioblastoma (GBM), contributing to chemotherapy and radiation resistance in GBM. Elucidating the underlying molecular mechanism of temozolomide (TMZ) resistance in EGFRvIII GBM could offer valuable insights for cancer treatment. METHODS: To elucidate the molecular mechanisms underlying EGFRvIII-mediated resistance to TMZ in GBM, we conducted a comprehensive analysis using Gene Expression Omnibus and The cancer genome atlas (TCGA) databases. Initially, we identified common significantly differentially expressed genes (DEGs) and prioritized those correlating significantly with patient prognosis as potential downstream targets of EGFRvIII and candidates for drug resistance. Additionally, we analyzed transcription factor expression changes and their correlation with candidate genes to elucidate transcriptional regulatory mechanisms. Using estimate method and databases such as Tumor IMmune Estimation Resource (TIMER) and CellMarker, we assessed immune cell infiltration in TMZ-resistant GBM and its relationship with candidate gene expression. In this study, we examined the expression differences of candidate genes in GBM cell lines following EGFRvIII intervention and in TMZ-resistant GBM cell lines. This preliminary investigation aimed to verify the regulatory impact of EGFRvIII on candidate targets and its potential involvement in TMZ resistance in GBM. RESULTS: Notably, GTPase Activating Rap/RanGAP Domain Like 3 (GARNL3) emerged as a key DEG associated with TMZ resistance and poor prognosis, with reduced expression correlating with altered immune cell profiles. Transcription factor analysis suggested Epiregulin (EREG) as a putative upstream regulator of GARNL3, linking it to EGFRvIII-mediated TMZ resistance. In vitro experiments confirmed EGFRvIII-mediated downregulation of GARNL3 and decreased TMZ sensitivity in GBM cell lines, further supported by reduced GARNL3 levels in TMZ-resistant GBM cells. CONCLUSION: GARNL3 downregulation in EGFRvIII-positive and TMZ-resistant GBM implicates its role in TMZ resistance, suggesting modulation of EREG/GARNL3 signaling as a potential therapeutic strategy.

10.
Nat Microbiol ; 9(8): 1954-1963, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38831032

RESUMO

Most of Earth's prokaryotes live under energy limitation, yet the full breadth of strategies that enable survival under such conditions remain poorly understood. Here we report the isolation of a bacterial strain, IA91, belonging to the candidate phylum Marine Group A (SAR406 or 'Candidatus Marinimicrobia') that is unable to synthesize the central cell wall compound peptidoglycan itself. Using cultivation experiments and microscopy, we show that IA91 growth and cell shape depend on other bacteria, deriving peptidoglycan, energy and carbon from exogenous muropeptide cell wall fragments released from growing bacteria. Reliance on exogenous muropeptides is traceable to the phylum's ancestor, with evidence of vertical inheritance across several classes. This dependency may be widespread across bacteria (16 phyla) based on the absence of key peptidoglycan synthesis genes. These results suggest that uptake of exogenous cell wall components could be a relevant and potentially common survival strategy in energy-limited habitats like the deep biosphere.


Assuntos
Bactérias , Parede Celular , Peptidoglicano , Parede Celular/metabolismo , Peptidoglicano/metabolismo , Bactérias/classificação , Bactérias/genética , Bactérias/metabolismo , Bactérias/isolamento & purificação , Filogenia , Água do Mar/microbiologia , Carbono/metabolismo , Organismos Aquáticos , Metabolismo Energético
11.
J Geriatr Cardiol ; 21(4): 431-442, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38800546

RESUMO

OBJECTIVE: To assess the feasibility and safety of the minimalistic approach to left atrial appendage occlusion (LAAO) guided by cardiac computed tomography angiography (CCTA). METHODS: Ninety consecutive patients who underwent LAAO, with or without CCTA-guided, were matched (1:2). Each step of the LAAO procedure in the computed tomography (CT) guidance group (CT group) was directed by preprocedural CT planning. In the control group, LAAO was performed using the standard method. All patients were followed up for 12 months, and device surveillance was conducted using CCTA. RESULTS: A total of 90 patients were included in the analysis, with 30 patients in the CT group and 60 matched patients in the control group. All patients were successfully implanted with Watchman devices. The mean ages for the CT group and the control group were 70.0 ± 9.4 years and 68.4 ± 11.9 years (P = 0.52), respectively. The procedure duration (45.6 ± 10.7 min vs. 58.8 ± 13.0 min, P < 0.001) and hospital stay (7.5 ± 2.4 day vs. 9.6 ± 2.8 day, P = 0.001) in the CT group was significantly shorter compared to the control group. However, the total radiation dose was higher in the CT group compared to the control group (904.9 ± 348.0 mGy vs. 711.9 ± 211.2 mGy, P = 0.002). There were no significant differences in periprocedural pericardial effusion (3.3% vs. 6.3%, P = 0.8) between the two groups. The rate of postprocedural adverse events (13.3% vs. 18.3%, P = 0.55) were comparable between both groups at 12 months follow-up. CONCLUSIONS: CCTA is capable of detailed LAAO procedure planning. Minimalistic LAAO with preprocedural CCTA planning was feasible and safe, with shortened procedure time and acceptable increased radiation and contras consumption. For patients with contraindications to general anesthesia and/or transesophageal echocardiography, this promising method may be an alternative to conventional LAAO.

12.
J Am Chem Soc ; 146(22): 15428-15437, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38795044

RESUMO

Chemical recycling to monomers (CRM) offers a promising closed-loop approach to transition from current linear plastic economy toward a more sustainable circular paradigm. Typically, this approach has focused on modulating the ceiling temperature (Tc) of monomers. Despite considerable advancements, polymers with low Tc often face challenges such as inadequate thermal stability, exemplified by poly(γ-butyrolactone) (PGBL) with a decomposition temperature of ∼200 °C. In contrast, floor temperature (Tf)-regulated polymers, particularly those synthesized via the ring-opening polymerization (ROP) of macrolactones, inherently exhibit enhanced thermodynamic stability as the temperature increases. However, the development of those Tf regulated chemically recyclable polymers remains relatively underexplored. In this context, by judicious design and efficient synthesis of a biobased macrocyclic diester monomer (HOD), we developed a type of Tf -regulated closed-loop chemically recyclable poly(ketal-ester) (PHOD). First, the entropy-driven ROP of HOD generated high-molar mass PHOD with exceptional thermal stability with a Td,5% reaching up to 353 °C. Notably, it maintains a high Td,5% of 345 °C even without removing the polymerization catalyst. This contrasts markedly with PGBL, which spontaneously depolymerizes back to the monomer above its Tc in the presence of catalyst. Second, PHOD displays outstanding closed-loop chemical recyclability at room temperature within just 1 min with tBuOK. Finally, copolymerization of pentadecanolide (PDL) with HOD generated high-performance copolymers (PHOD-co-PPDL) with tunable mechanical properties and chemical recyclability of both components.

13.
Chem Commun (Camb) ; 60(37): 4898-4901, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38629248

RESUMO

A heart-on-a-particle model based on multicompartmental microgel is proposed to simulate the heart microenvironment and study the cardiotoxicity of drugs. The relevant microgel was fabricated by a biocompatible microfluidic-based approach, where heart function-related HL-1 and HUVEC cells were arranged in separate compartments. Finally, the mechanism of aconitine-induced heart toxicity was elucidated using mass spectrometry and molecular biotechnology.


Assuntos
Aconitina , Células Endoteliais da Veia Umbilical Humana , Dispositivos Lab-On-A-Chip , Aconitina/química , Humanos , Cardiotoxicidade/etiologia , Linhagem Celular , Tamanho da Partícula , Sobrevivência Celular/efeitos dos fármacos
14.
Aging (Albany NY) ; 16(5): 4904-4919, 2024 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-38460957

RESUMO

Stem cell therapy requires massive-scale homogeneous stem cells under strict qualification control. However, Prolonged ex vivo expansion impairs the biological functions and results in senescence of mesenchymal stem cells (MSCs). We investigated the function of CTDSPL in the premature senescence process of MSCs and clarified that miR-18a-5p played a prominent role in preventing senescence of long-term cultured MSCs and promoting the self-renewal ability of MSCs. Over-expression of CTDSPL resulted in an enlarged morphology, up-regulation of p16 and accumulation of SA-ß-gal of MSCs. The reduced phosphorylated RB suggested cell cycle arrest of MSCs. All these results implied that CTDSPL induced premature senescence of MSCs. We further demonstrated that miR-18a-5p was a putative regulator of CTDSPL by luciferase reporter assay. Inhibition of miR-18a-5p promoted the expression of CTDSPL and induced premature senescence of MSCs. Continuous overexpression of miR-18a-5p improved self-renewal of MSCs by reducing ROS level, increased expression of Oct4 and Nanog, and promoted growth rate and differentiation capability. We reported for the first time that the dynamic interaction of miR-18a-5p and CTDSPL is crucial for stem cell senescence.


Assuntos
Células-Tronco Mesenquimais , MicroRNAs , MicroRNAs/genética , MicroRNAs/metabolismo , Diferenciação Celular/genética , Senescência Celular/genética , Regulação para Cima , Células-Tronco Mesenquimais/metabolismo
15.
ACS Sens ; 9(3): 1555-1564, 2024 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-38442411

RESUMO

Extracellular vesicle microRNAs (EV miRNAs) are critical noninvasive biomarkers for early cancer diagnosis. However, accurate cancer diagnosis based on bulk analysis is hindered by the heterogeneity among EVs. Herein, we report an approach for profiling single-EV multi-miRNA signatures by combining total internal reflection fluorescence (TIRF) imaging with a deep learning (DL) algorithm for the first time. This innovative technique allows for the precise characterization of EV miRNAs at the single-vesicle level, overcoming the challenges posed by EV heterogeneity. TIRF with high resolution and a signal-to-noise ratio can simultaneously detect multi-miRNAs in situ in individual EVs. DL algorithm avoids complicated and inaccurate artificial feature extraction, achieving automated high-resolution image analysis. Using this approach, we reveal that the main variation of EVs from 5 cancer cells and normal plasma is the triple-positive EV subpopulation, and the classification accuracy of single triple-positive EVs from 6 sources can reach above 95%. In the clinical cohort, 20 patients (5 lung cancer, 5 breast cancer, 5 cervical cancer, and 5 colon cancer) and 5 healthy controls are predicted with an overall accuracy of 100%. This single-EV strategy provides new opportunities for exploring more specific EV biomarkers to achieve cancer diagnosis and classification.


Assuntos
Neoplasias da Mama , Aprendizado Profundo , Vesículas Extracelulares , MicroRNAs , Humanos , Feminino , MicroRNAs/genética , Biomarcadores
16.
Anal Sci ; 40(6): 1167-1175, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38522044

RESUMO

Cu2+ as an important trace element plays an essential role in various biologic processes due to the unique redox active nature. For this reason, much effort has been made to develop effective methods for Cu2+ detection. In this study, a novel structure fluorescent chemosensor, 1-(6-(((5-(5, 5-difluoro-1, 3, 7, 9-tetramethyl-5H-4λ4, 5λ4-dipyrrolo[1, 2-c:2', 1'-f][1, 3, 2] diazaborinin-10-yl)quinolin-8-yl)oxy)methyl)pyridin-2-yl)-N, N-bis(pyridin-2-ylmethyl)methanamine (1), was synthesized and characterized by 1H and 13C nuclear magnetic resonance spectroscopy, and electrospray ionization mass spectrometry. Sensor 1 showed an obviously "on-off" fluorescence response to Cu2+ with a 1:1 binding stoichiometry by UV-vis and fluorescence spectrophotometry. The detection limit of sensor 1 to Cu2+ was determined to be 1.9 µM, and the stable pH range for Cu2+ detection was from 3 to 13. Sensor 1 can be used for recognition and detection of tyrosinase in potatoes.


Assuntos
Cobre , Corantes Fluorescentes , Monofenol Mono-Oxigenase , Solanum tuberosum , Espectrometria de Fluorescência , Cobre/química , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Concentração de Íons de Hidrogênio , Solanum tuberosum/química , Monofenol Mono-Oxigenase/metabolismo , Monofenol Mono-Oxigenase/química , Limite de Detecção
17.
Sci Rep ; 14(1): 7078, 2024 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-38528192

RESUMO

Mouse auditory cortex is composed of six sub-fields: primary auditory field (AI), secondary auditory field (AII), anterior auditory field (AAF), insular auditory field (IAF), ultrasonic field (UF) and dorsoposterior field (DP). Previous studies have examined thalamo-cortical connections in the mice auditory system and learned that AI, AAF, and IAF receive inputs from the ventral division of the medial geniculate body (MGB). However, the functional and thalamo-cortical connections between nonprimary auditory cortex (AII, UF, and DP) is unclear. In this study, we examined the locations of neurons projecting to these three cortical sub-fields in the MGB, and addressed the question whether these cortical sub-fields receive inputs from different subsets of MGB neurons or common. To examine the distributions of projecting neurons in the MGB, retrograde tracers were injected into the AII, UF, DP, after identifying these areas by the method of Optical Imaging. Our results indicated that neuron cells which in ventral part of dorsal MGB (MGd) and that of ventral MGB (MGv) projecting to UF and AII with less overlap. And DP only received neuron projecting from MGd. Interestingly, these three cortical areas received input from distinct part of MGd and MGv in an independent manner. Based on our foundings these three auditory cortical sub-fields in mice may independently process auditory information.


Assuntos
Córtex Auditivo , Corpos Geniculados , Camundongos , Animais , Corpos Geniculados/fisiologia , Córtex Auditivo/fisiologia , Neurônios , Neuritos , Vias Auditivas/fisiologia , Tálamo/fisiologia
18.
Phys Rev E ; 109(2-2): 025205, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38491683

RESUMO

In this study, the spatiotemporal evolution of full cycle of high-intensity dc argon arc discharge at atmospheric pressure is investigated by using a transferred arc device, which is easy to be directly observed in the experiment. Combining the voltage and current waveforms with high-speed images, the full cycle evolution process of high-intensity atmospheric dc arc can be divided into five different stages: breakdown pulse stage, cathode heating stage, current climbing stage, stable arc discharge stage, and finally arc extinguishing stage. The characteristics of each different stage are analyzed in detail through the electrical properties, high-speed pictures, and spectroscopic measurements. The results show that the strong luminescence region develops from the vicinity of cathode and anode to the middle in the breakdown pulse stage, which is explained from the spatiotemporal evolution of distributions of excited argon atom and ions. The development velocity of emission intensity of argon ions is mainly determined by the dominant stepwise ionization process. Then the cathode heating stage appears with many bright and nonuniformly distributed light spots on the cathode surface, and the electron emission mechanism of cathode gradually changes to the thermionic emission as the surface temperature rises. With the increase of arc current, the discharge channel significantly expands, then becomes stable due to the increment of the Lorentz force. The characteristics of arc extinguishing stage are clarified in terms of the decay of charged particles density.

19.
Artigo em Inglês | MEDLINE | ID: mdl-38430605

RESUMO

Prolyl hydroxylase domain 2 (PHD2) is an important enzyme in the human body that perceives changes in oxygen concentration and regulates response in hypoxic environments. Evaluation of PHD2 inhibitory activity of natural products is crucial for drug development of hypoxia related diseases. At present, the detection of low concentration of α-ketoglutaric acid (the substrate of PHD2 enzymatic reaction) requires derivatization reactions or sample pretreatment, which undoubtedly increases the workload of PHD2 inhibitory activity evaluation. In this paper, a direct detection approach of α-ketoglutaric acid was established by using the online stacking strategy of capillary electrophoresis to evaluate the PHD2 inhibitory activity of natural products. Under optimized conditions, detection of a single sample can be achieved within 2 min. By calculation, the intraday precision RSD of the apparent electrophoretic mobility and peak areas of α-ketoglutaric acid are 0.92 % and 0.79 %, respectively, and the interday RSD were 1.27 % and 0.96 % respectively. The recoveries of the present approach were 97.9-105.2 %, and the LOQ and LOD were 2.0 µM and 5.0 µM, respectively. Furthermore, this approach was applied for the evaluation of inhibitory activity of PHD2 for 13 natural products, and PHD2 inhibitory activity of salvianolic acid A was firstly reported. The present work not only realizes evaluation of PHD2 inhibitory activity through direct detection of α-ketoglutaric acid, but also provides technical support for the discovery of potential drug molecules in hypoxia related diseases.


Assuntos
Produtos Biológicos , Eletroforese Capilar , Prolina Dioxigenases do Fator Induzível por Hipóxia , Ácidos Cetoglutáricos , Humanos , Produtos Biológicos/farmacologia , Eletroforese Capilar/métodos , Prolina Dioxigenases do Fator Induzível por Hipóxia/antagonistas & inibidores , Ácidos Cetoglutáricos/análise
20.
Front Comput Neurosci ; 18: 1356447, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38404511

RESUMO

Colorectal polyp is an important early manifestation of colorectal cancer, which is significant for the prevention of colorectal cancer. Despite timely detection and manual intervention of colorectal polyps can reduce their chances of becoming cancerous, most existing methods ignore the uncertainties and location problems of polyps, causing a degradation in detection performance. To address these problems, in this paper, we propose a novel colorectal image analysis method for polyp diagnosis via PAM-Net. Specifically, a parallel attention module is designed to enhance the analysis of colorectal polyp images for improving the certainties of polyps. In addition, our method introduces the GWD loss to enhance the accuracy of polyp diagnosis from the perspective of polyp location. Extensive experimental results demonstrate the effectiveness of the proposed method compared with the SOTA baselines. This study enhances the performance of polyp detection accuracy and contributes to polyp detection in clinical medicine.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA