Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 116
Filtrar
Más filtros

Bases de datos
País/Región como asunto
Tipo del documento
País de afiliación
Intervalo de año de publicación
1.
Mol Biol Evol ; 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39162340

RESUMEN

Modern humans have experienced explosive population growth in the past thousand years. We hypothesized that recent human populations have inhabited environments with relaxation of selective constraints, possibly due to the more abundant food supply after the Last Glacial Maximum. The ratio of nonsynonymous to synonymous mutations (N/S ratio) is a useful and common statistic for measuring selective constraints. In this study, we reconstructed a high-resolution phylogenetic tree using a total of 26,419 East Eurasian mtDNA genomes, which were further classified into expansion and non-expansion groups on the basis of the frequencies of their founder lineages. We observed a much higher N/S ratio in the expansion group, especially for nonsynonymous mutations with moderately deleterious effects, indicating a weaker effect of purifying selection in the expanded clades. However, this observation on N/S ratio was unlikely in computer simulations where all individuals were under the same selective constraints. Thus, we argue that the expanded populations were subjected to weaker selective constraints than the non-expanded populations were. The mildly deleterious mutations were retained during population expansion, which could have a profound impact on present-day disease patterns.

2.
Mol Biol Evol ; 41(7)2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38885310

RESUMEN

Large-scale genomic projects and ancient DNA innovations have ushered in a new paradigm for exploring human evolutionary history. However, the genetic legacy of spatiotemporally diverse ancient Eurasians within Chinese paternal lineages remains unresolved. Here, we report an integrated Y-chromosome genomic database encompassing 15,563 individuals from both modern and ancient Eurasians, including 919 newly reported individuals, to investigate the Chinese paternal genomic diversity. The high-resolution, time-stamped phylogeny reveals multiple diversification events and extensive expansions in the early and middle Neolithic. We identify four major ancient population movements, each associated with technological innovations that have shaped the Chinese paternal landscape. First, the expansion of early East Asians and millet farmers from the Yellow River Basin predominantly carrying O2/D subclades significantly influenced the formation of the Sino-Tibetan people and facilitated the permanent settlement of the Tibetan Plateau. Second, the dispersal of rice farmers from the Yangtze River Valley carrying O1 and certain O2 sublineages reshapes the genetic makeup of southern Han Chinese, as well as the Tai-Kadai, Austronesian, Hmong-Mien, and Austroasiatic people. Third, the Neolithic Siberian Q/C paternal lineages originated and proliferated among hunter-gatherers on the Mongolian Plateau and the Amur River Basin, leaving a significant imprint on the gene pools of northern China. Fourth, the J/G/R paternal lineages derived from western Eurasia, which were initially spread by Yamnaya-related steppe pastoralists, maintain their presence primarily in northwestern China. Overall, our research provides comprehensive genetic evidence elucidating the significant impact of interactions with culturally distinct ancient Eurasians on the patterns of paternal diversity in modern Chinese populations.


Asunto(s)
Pueblo Asiatico , Cromosomas Humanos Y , Migración Humana , Humanos , China , Pueblo Asiatico/genética , Masculino , Cromosomas Humanos Y/genética , ADN Antiguo/análisis , Herencia Paterna , Filogenia , Pueblos del Este de Asia
3.
Nature ; 569(7754): 112-115, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-31019300

RESUMEN

The study of language origin and divergence is important for understanding the history of human populations and their cultures. The Sino-Tibetan language family is the second largest in the world after Indo-European, and there is a long-running debate about its phylogeny and the time depth of its original divergence1. Here we perform a Bayesian phylogenetic analysis to examine two competing hypotheses of the origin of the Sino-Tibetan language family: the 'northern-origin hypothesis' and the 'southwestern-origin hypothesis'. The northern-origin hypothesis states that the initial expansion of Sino-Tibetan languages occurred approximately 4,000-6,000 years before present (BP; taken as AD 1950) in the Yellow River basin of northern China2-4, and that this expansion is associated with the development of the Yangshao and/or Majiayao Neolithic cultures. The southwestern-origin hypothesis states that an early expansion of Sino-Tibetan languages occurred before 9,000 years BP from a region in southwest Sichuan province in China5 or in northeast India6, where a high diversity of Tibeto-Burman languages exists today. Consistent with the northern-origin hypothesis, our Bayesian phylogenetic analysis of 109 languages with 949 lexical root-meanings produced an estimated time depth for the divergence of Sino-Tibetan languages of approximately 4,200-7,800 years BP, with an average value of approximately 5,900 years BP. In addition, the phylogeny supported a dichotomy between Sinitic and Tibeto-Burman languages. Our results are compatible with the archaeological records, and with the farming and language dispersal hypothesis7 of agricultural expansion in China. Our findings provide a linguistic foothold for further interdisciplinary studies of prehistoric human activity in East Asia.


Asunto(s)
Teorema de Bayes , Lenguaje/historia , Modelos Teóricos , Filogenia , Arqueología , China , Evolución Cultural/historia , Historia Antigua , Humanos , Tibet
4.
BMC Biol ; 22(1): 59, 2024 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-38475771

RESUMEN

BACKGROUND: Hmong-Mien (HM) speakers are linguistically related and live primarily in China, but little is known about their ancestral origins or the evolutionary mechanism shaping their genomic diversity. In particular, the lack of whole-genome sequencing data on the Yao population has prevented a full investigation of the origins and evolutionary history of HM speakers. As such, their origins are debatable. RESULTS: Here, we made a deep sequencing effort of 80 Yao genomes, and our analysis together with 28 East Asian populations and 968 ancient Asian genomes suggested that there is a strong genetic basis for the formation of the HM language family. We estimated that the most recent common ancestor dates to 5800 years ago, while the genetic divergence between the HM and Tai-Kadai speakers was estimated to be 8200 years ago. We proposed that HM speakers originated from the Yangtze River Basin and spread with agricultural civilization. We identified highly differentiated variants between HM and Han Chinese, in particular, a deafness-related missense variant (rs72474224) in the GJB2 gene is in a higher frequency in HM speakers than in others. CONCLUSIONS: Our results indicated complex gene flow and medically relevant variants involved in the HM speakers' evolution history.


Asunto(s)
Conexina 26 , Pool de Genes , Genética de Población , Humanos , Pueblo Asiatico , China , Genómica
5.
Brief Bioinform ; 23(1)2022 01 17.
Artículo en Inglés | MEDLINE | ID: mdl-34727570

RESUMEN

Brain disease gene identification is critical for revealing the biological mechanism and developing drugs for brain diseases. To enhance the identification of brain disease genes, similarity-based computational methods, especially network-based methods, have been adopted for narrowing down the searching space. However, these network-based methods only use molecular networks, ignoring brain connectome data, which have been widely used in many brain-related studies. In our study, we propose a novel framework, named brainMI, for integrating brain connectome data and molecular-based gene association networks to predict brain disease genes. For the consistent representation of molecular-based network data and brain connectome data, brainMI first constructs a novel gene network, called brain functional connectivity (BFC)-based gene network, based on resting-state functional magnetic resonance imaging data and brain region-specific gene expression data. Then, a multiple network integration method is proposed to learn low-dimensional features of genes by integrating the BFC-based gene network and existing protein-protein interaction networks. Finally, these features are utilized to predict brain disease genes based on a support vector machine-based model. We evaluate brainMI on four brain diseases, including Alzheimer's disease, Parkinson's disease, major depressive disorder and autism. brainMI achieves of 0.761, 0.729, 0.728 and 0.744 using the BFC-based gene network alone and enhances the molecular network-based performance by 6.3% on average. In addition, the results show that brainMI achieves higher performance in predicting brain disease genes compared to the existing three state-of-the-art methods.


Asunto(s)
Enfermedad de Alzheimer , Conectoma , Trastorno Depresivo Mayor , Encéfalo/diagnóstico por imagen , Conectoma/métodos , Humanos , Imagen por Resonancia Magnética/métodos
6.
Analyst ; 149(13): 3651-3660, 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38814120

RESUMEN

Monitoring methods for beta-lactam (ß-lactam) antibiotics, especially for ampicillin (AMP), with simple operation and sensitivity for realtime applications are highly required. To address this need, antioxidant carbon dots (E-CDs) with excellent fluorescence properties were synthesized using citric acid and ethylenediamine as raw materials. With a quantum yield of 81.97%, E-CDs exhibited a specific and sensitive response to ˙OH. The quenched fluorescence of E-CDs by the formed ˙OH could be restored through a competition reaction with AMP. Leveraging the signal-quenching strategy of E-CDs, H2O2, and Fe2+, a fluorescence signal-on strategy was developed using AMP as the fluorescence recovery agent for the sensitive detection of AMP. The mechanism of the quenching of E-CDs by ˙OH was attributed to the damaging effect of ˙OH on E-CDs. Under optimal conditions, the detection limit of this method for AMP was determined to be 0.38 µg mL-1. This method was successful in drug quality control and the spiked detection of AMP in lake water, milk, and sea cucumber, presenting a viable option for convenient and rapid antibiotic monitoring methods.


Asunto(s)
Ampicilina , Carbono , Límite de Detección , Puntos Cuánticos , Espectrometría de Fluorescencia , Carbono/química , Ampicilina/análisis , Ampicilina/química , Puntos Cuánticos/química , Espectrometría de Fluorescencia/métodos , Animales , Antioxidantes/análisis , Antioxidantes/química , Leche/química , Peróxido de Hidrógeno/química , Peróxido de Hidrógeno/análisis , Radical Hidroxilo/química , Radical Hidroxilo/análisis , Antibacterianos/análisis , Antibacterianos/química , Colorantes Fluorescentes/química , Ácido Cítrico/química , Fluorescencia , Etilenodiaminas
7.
J Fluoresc ; 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38300482

RESUMEN

Diabetic mellitus management extends beyond blood glucose monitoring to the essential task of mitigating the overexpression of reactive oxygen species (ROS), particularly vital for cellular repair, especially within the nervous system. Herein, antioxidant carbon dots (Arg-CDs) were designed and prepared using anhydrous citric acid, L-arginine, and ethylenediamine as sources through a hydrothermal method. Arg-CDs exhibited excellent scavenging ability to 2,2-Diphenyl-1-picrylhydrazyl (DPPH∙), and fluorescence response to hydroxyl radicals (∙OH), a characteristic representative of reactive oxygen species (ROS). Assisted by glucose oxidase and Fe2+, Arg-CDs showed a sensitive and selective response to glucose. The quenching mechanism of Arg-CDs by formed ∙OH was based on the static quenching effect (SQE). The analytical performance of this method for glucose detection encompassed a wide linear range (0.3-15 µM), a low practical limit of detection (0.1 µM) and practical applicability for blood glucose monitoring. In an in vitro model employing glial cells (BV2 cells), it was observed that high glucose medium led to notable cellular damage ascribed to the excessive ROS production from hyperglycemia. The diminished and apoptotic glial cells were gradually recovered by adding increased contents of Arg-CDs. This work illustrates a promising area that designs effective carbon dots with antioxidant capacity for the dual applications of detection and cell repairing based on the utilization of antioxidant activity.

8.
Support Care Cancer ; 32(3): 194, 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38411723

RESUMEN

To assess the level of supportive care needs of caregivers of colorectal cancer patients and explore the related key influencing factors. Totaling 283 caregivers of patients with colorectal cancer were investigated in this study. Firstly, caregivers were invited to complete a set of questionnaires, including the general information questionnaire, the Supportive Care Needs Survey-Partners and the Caregivers of cancer patients, the Caregiver Preparedness Scale, the Benefit Finding Scale, and the Comprehensive Score for Financial Toxicity. Univariate and multivariate linear regression were performed to investigate the associated factors of supportive care needs. The caregivers of patients with colorectal cancer have a moderate level of needs, scored at 2.71 ± 0.42. Caregiver preparedness, benefit finding, and financial toxicity were significantly negatively associated with the supportive care needs of caregivers (r = - 0.555, P < 0.001; r = - 0.534, P < 0.001; and r = - 0.615, P < 0.001, respectively). Our multivariate regression analysis identified some factors that directly affected the supportive care needs of caregivers, including the duration of illness, tumor stage, the age and educational level of caregivers, caregiver preparedness, benefit finding, and financial toxicity (R2 = 0.574, F = 23.337, P < 0.001). Supportive care needs are common among caregivers of colorectal cancer patients. Higher caregiver preparedness, benefit finding, and financial toxicity tend to ease these needs. Healthcare workers should have an in-depth understanding of the needs of caregivers of colorectal cancer patients and actively provide targeted financial/informational/technical/emotional support to promote nursing skills and reduce caregivers' burdens.


Asunto(s)
Cuidadores , Neoplasias Colorrectales , Humanos , Estudios Transversales , Personal de Salud , Carga del Cuidador , Neoplasias Colorrectales/terapia
9.
Sensors (Basel) ; 24(3)2024 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-38339694

RESUMEN

Metal oxide semiconductor hetero- and homojunctions are commonly constructed to improve the performance of hydrogen sensors at room temperature. In this study, a simple two-step hydrothermal method was employed to prepare TiO2 films with homojunctions of rutile and anatase phases (denoted as TiO2-R/A). Then, the microstructure of anatase-phase TiO2 was altered by controlling the amount of hydrochloric acid to realize a more favorable porous structure for charge transport and a larger surface area for contact with H2. The sensor used a Pt interdigital electrode. At an optimal HCl dosage (25 mL), anatase-phase TiO2 uniformly covered rutile-phase TiO2 nanorods, resulting in a greater response to H2 at 2500 ppm compared with that of a rutile TiO2 nanorod sensor by a factor of 1153. The response time was 21 s, mainly because the homojunction formed by the TiO2 rutile and anatase phases increased the synergistic effect of the charge transfer and potential barrier between the two phases, resulting in the formation of more superoxide (O2-) free radicals on the surface. Furthermore, the porous structure increased the surface area for H2 adsorption. The TiO2-R/A-based sensor exhibited high selectivity, long-term stability, and a fast response. This study provides new insights into the design of commercially competitive hydrogen sensors.

10.
Proc Biol Sci ; 290(2002): 20230606, 2023 07 12.
Artículo en Inglés | MEDLINE | ID: mdl-37403498

RESUMEN

The origin of tone, also known as tonogenesis, has long been a topic of great interest in language evolution and human cognition studies. Several linguistic studies of tonal languages have proposed various hypotheses that tonal origin may be related to different changes of phonological structures. However, such hypotheses have not been quantitatively tested in an evolutionary framework. Here, we conducted phylogenetic comparative analyses to assess the likelihood of different hypotheses of tonogenetic mechanisms across 106 Sino-Tibetan languages, of which approximately 70% are tonal. Our results showed that the presence of tones has a strong phylogenetic pattern and that Proto-Sino-Tibetan languages were most likely non-tonal. Our findings identified that tonal origin was strongly associated with the evolution of specific phonological structures, such as the loss of syllable-final consonants and voice quality on vowels. Furthermore, we found that tonal origin probably did not influence the diversification rates of Sino-Tibetan languages. These findings enabled us to better understand that tone arose as a compensatory mechanism for the structural organization and evolution of languages.


Asunto(s)
Lenguaje , Percepción del Habla , Humanos , Filogenia , Lingüística , Cognición , Probabilidad
11.
J Fluoresc ; 2023 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-37530930

RESUMEN

The establishment of a convenient and effective detection method for doxycycline (DC) holds significant importance in drug monitoring and drug residue assessment. In this work, carbon quantum dots (CQDs) with excellent and stable luminescence performance (the quantum yield of CQDs was 21.8%) were synthesized by the melting method and employed as probes to monitor the fluorescence intensity variations before and after the introduction of DC. A fluorescence analytical method based on the internal filtration effect (IFE) was developed for DC determination. The mechanism of DC quenching CQDs was verified using fluorescence lifetime tests, absorption spectroscopy, and evaluation of internal filtration parameters. After optimizing experimental conditions, it was found that the DC concentration (CDC) exhibited a good linear relationship with the fluorescence quenching efficiency ((F0-F)/F0) of CQDs in the range of 5-30 µM. The fitted linear equation was Y = 0.01249*CDC+0.03625, R2 = 0.9987, and the detection limit was 2.343 µM (n = 8). This developed method has been successfully applied to accurately determine DC concentrations in both doxycycline hydrochloride tablets and human serum samples. It stands out for its simplicity, rapidity, and acceptable detection performance. Due to its advantages, this method holds great promise for application in the biomedical field for monitoring DC drug concentrations and ensuring quality control.

12.
Oral Dis ; 2023 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-37357358

RESUMEN

OBJECTIVE: Obesity can affect periodontal tissues and exacerbate periodontitis. Pyroptosis, a newly identified type of inflammatory cell death, is involved in the development of periodontal inflammation. The saturated fatty acid palmitic acid (PA) is elevated in obese patients. The effect of PA on pyroptosis in periodontal ligament cells (PDLCs) and its underlying mechanisms remain unknown. MATERIALS AND METHODS: Human PDLCs were isolated from healthy individuals and cultured for experiments. The effects of PA on PDLC pyroptosis and the underlying mechanisms were examined by transmission electron microscopy, quantitative real-time PCR and western blotting. RESULTS: The morphology of PDLCs in the PA group indicated pyroptotic characteristics, including swollen cells, plasma membrane rupture and changes in subcellular organelles. PA induced inflammatory responses in PDLCs, as indicated by an increase in IL-1ß in the cell culture supernatant. Furthermore, we found that the pyroptosis-related proteins caspase-1, caspase-4 and GSDMD were involved in PA-induced cell death. GSDMD and caspase-4 inhibitors alleviated pyroptotic death of PDLCs. Moreover, PA promoted NF-κB P65 phosphorylation. A NF-κB inhibitor decreased IL-1ß expression and partly rescued cell death induced by PA. CONCLUSION: PA activated the NF-κB pathway and induced the inflammatory response in PDLCs. Caspase-4/GSDMD mediated PDLC pyroptosis induced by PA.

13.
BMC Public Health ; 23(1): 859, 2023 05 11.
Artículo en Inglés | MEDLINE | ID: mdl-37170239

RESUMEN

BACKGROUND: Alcohol related liver disease (ARLD) is one of the major chronic liver diseases worldwide. This review aimed to describe the global prevalence, incidence, and outcomes of ARLD. METHODS: Medline, Embase, The Cochrane Library, and China National Knowledge Infrastructure (CNKI) were searched from inception to May 31, 2022. The language was restricted to English or Chinese. According to the criteria, articles describing the basic characteristics of the population were selected. Two reviewers extracted the data independently. RESULTS: A total of 372 studies were identified: 353 were used for prevalence analysis, 7 were used for incidence analysis, and 114 were used to for outcome analysis. The prevalence of ARLD worldwide was 4.8%. The prevalence in males was 2.9%, which was higher than female (0.5%). Among the ethnic groups, the percentage was highest in Caucasians (68.9%). Alcoholic liver cirrhosis comprised the highest proportion in the disease spectrum of ARLD at 32.9%. The prevalence of ascites in ARLD population was highest (25.1%). The ARLD population who drinking for > 20 years accounted for 54.8%, and the average daily alcohol intake was 146.6 g/d. About 59.5% of ARLD patients were current or former smokers, and 18.7% were complicated with hepatitis virus infection. The incidence was 0.208/1000 person-years. The overall mortality was 23.9%, and the liver-related mortality was 21.6%. CONCLUSION: The global prevalence of ARLD was 4.8% and was affected by sex, region, drinking years, and other factors. Therefore, removing the factors causing a high disease prevalence is an urgent requisite. TRIAL REGISTRATION: PROSPERO Nr: CRD42021286192.


Asunto(s)
Hepatopatías , Masculino , Humanos , Femenino , Prevalencia , Incidencia , Hepatopatías/epidemiología , China
14.
Chem Pharm Bull (Tokyo) ; 71(11): 812-818, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37704432

RESUMEN

Tyrosinase (TYR) plays a pivotal role in the biosynthesis of melanin, and its activity level holds critical implications for vitiligo, melanoma cancer, and food nutritional value. The sensitive determination of TYR activity is of great significance for both fundamental research and clinical investigations. In this work, we successfully synthesized silicon-doped carbon quantum dots (Si-CQDs) through a one-pot hydrothermal method with trans-aconitic acid as carbon source and N-[3-(trimethoxysilyl)propyl]ethylenediamine as the dopant, exhibiting remarkable fluorescence quantum yield (QY) and photostability. Correspondingly, Si-CQDs were used as a probe to construct a sensitive, rapid, and user-friendly fluorescence method for TYR detection. The method relied on the oxidation of isoprenaline (ISO) by TYR, where Si-CQDs were employed as a highly efficient probe. The testing mechanism was the internal filtering effect (IFE) observed between Si-CQDs and the oxidative system of ISO and TYR. Under the optimized conditions, the fluorescence strategy exhibited a detection range of 0.05-2.0 U/mL for TYR with a limit of detection (LOD) of 0.041 U/mL. Furthermore, we successfully demonstrated the accurate determination of TYR levels in human serum, showcasing the promising potential of this method in various practical scenarios.


Asunto(s)
Técnicas Biosensibles , Puntos Cuánticos , Humanos , Monofenol Monooxigenasa , Carbono , Silicio , Técnicas Biosensibles/métodos , Nitrógeno , Espectrometría de Fluorescencia/métodos
15.
Int J Mol Sci ; 24(6)2023 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-36982301

RESUMEN

Psb28 is a soluble protein in the photosystem II (PSII) complex, but its role in the drought stress response of wheat remains unclear. Here, we functionally characterized the TaPsb28 gene, which positively regulates drought tolerance in wheat. When the full-length 546-bp TaPsb28 cDNA was transferred into Arabidopsis thaliana, it was located in the guard cell chloroplast around the stroma. Overexpression of TaPsb28 conferred drought tolerance, as exhibited by the increases in the survival rate. Transgenic plants maintained lower MDA content and higher chlorophyll content by inducing chlorophyll synthase (ChlG) gene transcription. The content of abscisic acid (ABA) and zeatin increased significantly in wild-type (WT) plants under drought stress, and the transcriptional expression levels of RD22, dihydroflavonol 4-reductase (DFR) and anthocyanin reductase (ANR) genes were induced, thus enhancing the contents of endogenous cyanidin, delphinidin, and proanthocyanidins. However, in transgenic plants, although anthocyanins were further aggregated, the ABA increase was inhibited, zeatin was restored to the control level under drought stress, and stomatal closure was promoted. These findings indicate ABA and zeatin have opposite synergistic effects in the process of drought tolerance caused by TaPsb28 because only after the effect of zeatin is alleviated can ABA better play its role in promoting anthocyanin accumulation and stomatal closure, thus enhancing the drought tolerance of transgenic plants. The results suggest that overexpression of TaPsb28 exerts a positive role in the drought response by influencing the functional metabolism of endogenous hormones. The understanding acquired through the research laid a foundation for further in-depth investigation of the function of TaPsb28 in drought resistance in wheat, especially its relationship with anthocyanidin accumulation.


Asunto(s)
Arabidopsis , Arabidopsis/fisiología , Antocianinas/farmacología , Resistencia a la Sequía , Triticum/fisiología , Zeatina/farmacología , Estrés Fisiológico , Plantas Modificadas Genéticamente/metabolismo , Ácido Abscísico/metabolismo , Sequías , Oxidorreductasas/metabolismo , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/metabolismo
16.
Bioorg Med Chem ; 54: 116579, 2022 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-34954618

RESUMEN

Four series of molecular hybrids (37 final products) of neo-tanshinlactone, a natural product extracted from Salvia miltiorrhiza Bunge, and known PD-1/PD-L1 interaction inhibitors were prepared as possible chemotherapeutic agents against triple negative breast cancer. Screening using a homogenous time-resolved fluorescence method resulted in three lead compounds (MZ52 IC50 74 ± 4 nM; MZ58 IC50 134 ± 17 nM; MZ61 IC50 225 ± 19 nM). With less T cell cytotoxicity and effects in activating CD8+ T cells in a T cell proliferation assay and a functionality experiment, MZ58 was selected as the best candidate for animal experiments. MZ58 exhibited antitumor effects in a subcutaneous transplantation tumor model as well as effects in reducing T cell exhaustion. In conclusion, after in vivo and in vitro experiments, we successfully acquired an effective candidate (MZ58) showing antitumor effects with low cytotoxicity toward T cells as well as the ability to activate CD8+ T cells and reduce T cell exhaustion.


Asunto(s)
Antineoplásicos/farmacología , Antígeno B7-H1/antagonistas & inhibidores , Diseño de Fármacos , Furanos/farmacología , Inhibidores de Puntos de Control Inmunológico/farmacología , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Pironas/farmacología , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Antígeno B7-H1/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Furanos/síntesis química , Furanos/química , Humanos , Inhibidores de Puntos de Control Inmunológico/síntesis química , Inhibidores de Puntos de Control Inmunológico/química , Masculino , Ratones , Ratones Endogámicos C57BL , Estructura Molecular , Receptor de Muerte Celular Programada 1/metabolismo , Pironas/síntesis química , Pironas/química , Relación Estructura-Actividad
17.
Molecules ; 27(23)2022 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-36500515

RESUMEN

Obstructive sleep apnea (OSA) is a common syndrome that features a complex etiology and set of mechanisms. Here we summarized the molecular pathogenesis of OSA, especially the prospective mechanism of upper? airway dilator fatigue and the current breakthroughs. Additionally, we also introduced the molecular mechanism of OSA in terms of related studies on the main signaling pathways and epigenetics alterations, such as microRNA, long non-coding RNA, and DNA methylation. We also reviewed small molecular compounds, which are potential targets for gene regulations in the future, that are involved in the regulation of OSA. This review will be beneficial to point the way for OSA research within the next decade.


Asunto(s)
MicroARNs , Apnea Obstructiva del Sueño , Humanos , Patología Molecular , Apnea Obstructiva del Sueño/genética , Apnea Obstructiva del Sueño/patología , Epigénesis Genética , MicroARNs/genética , Metilación de ADN , Sueño/fisiología
18.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 53(4): 726-731, 2022 Jul.
Artículo en Zh | MEDLINE | ID: mdl-35871748

RESUMEN

Screening for and identifying patients with Parkinson's disease (PD) at an early stage and forming accurate diagnosis of PD during the course of the progression of the disease are of essential importance but still remain challenging for the clinical diagnosis and treatment of PD. One of the common clinical manifestations of PD is speech impairment, or voice impairment. Thanks to the recent advances in the field of acoustic analysis, a large number of acoustic parameters have been proposed for evaluating speech impairment quantitatively. Early identification and accurate diagnosis of PD was henceforth made possible through the application of speech acoustic analysis. Herein, we summarized the latest research findings on the application of acoustic analysis in PD diagnosis. We reported some acoustic parameters commonly used in the evaluation of voice impairment in PD patients. Then, we presented the diagnostic value of acoustic analysis in developing accurate diagnosis, early screening and differential diagnosis. Furthermore, we discussed the drawbacks and prospects of current studies, intending to enhance understanding of acoustic analysis of PD patients and its potential diagnostic values.


Asunto(s)
Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/tratamiento farmacológico , Habla , Acústica del Lenguaje , Trastornos del Habla/diagnóstico , Trastornos del Habla/terapia
19.
J Periodontal Res ; 56(4): 656-666, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33604902

RESUMEN

BACKGROUND AND OBJECTIVE: The application of curcumin is limited by its instability. Mono-carbonyl analogues of curcumin (MCACs) are structurally stable, yet the intermediate bridging ketones in their skeletons account for increased toxicity. This study aimed to synthesize and screen MCACs that exhibit low cytotoxicity and high antioxidant ability, and the effects of MCACs on experimental periodontitis were also investigated. MATERIALS AND METHODS: The cytotoxicity of MCACs on MC3 T3-E1 was determined by MTT assay. The antioxidant capacity was investigated by the cell viability against H2 O2 -induced damage and the level of reactive oxygen species (ROS) and malondialdehyde (MDA). The localization and protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) was detected by immunofluorescence and western blot, respectively. In addition, MCAC was intragastrically administrated in rats with ligature-induced experimental periodontitis. The effects were assessed by bone resorption, as well as the immunohistology staining of inflammatory and oxidative stress markers. RESULTS: MCACs with cyclopentanone and containing pyrone showed lower toxicity than natural curcumin were synthesized (1A-10A, 1H-10H), among which, 1A exhibited the most potent cytoprotective effect against H2 O2 -induced damage. Such effects could be explained by the reduced MDA and ROS level, possibly through the nucleus translocation of Nrf2 and the induction of HO-1. Micro-CT results further indicated that 1A significantly reduced bone loss, along with an increased level of Nrf2 and HO-1, and decreased TNF-α and IL-1ß. CONCLUSION: The present study has synthesized a novel antioxidant MCAC 1A with good biosafety and stability. MCAC 1A could serve as a host response modulator with preventive and protective effects on periodontitis.


Asunto(s)
Curcumina , Periodontitis , Animales , Antioxidantes/farmacología , Curcumina/farmacología , Hemo-Oxigenasa 1/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo , Periodontitis/tratamiento farmacológico , Periodontitis/prevención & control , Ratas , Especies Reactivas de Oxígeno
20.
Sensors (Basel) ; 21(8)2021 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-33924465

RESUMEN

Accurate segmentation of entity categories is the critical step for 3D scene understanding. This paper presents a fast deep neural network model with Dense Conditional Random Field (DCRF) as a post-processing method, which can perform accurate semantic segmentation for 3D point cloud scene. On this basis, a compact but flexible framework is introduced for performing segmentation to the semantics of point clouds concurrently, contribute to more precise segmentation. Moreover, based on semantics labels, a novel DCRF model is elaborated to refine the result of segmentation. Besides, without any sacrifice to accuracy, we apply optimization to the original data of the point cloud, allowing the network to handle fewer data. In the experiment, our proposed method is conducted comprehensively through four evaluation indicators, proving the superiority of our method.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA