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1.
Inorg Chem ; 63(11): 5281-5293, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38430109

RESUMO

The attributes of good solubility and the redox-neutral nature of molten salt fluxes enable them to be useful for the synthesis of novel crystalline actinide compounds. In this work, a flux growth method under an inert atmosphere is proposed to explore the valence diversity of uranium, and a series of five uranium silicate structures, [K3Cl][(UVIO2)(Si4O10)] (1), Cs3[(UVO2)(Si4O10)] (2), K2[UIV(Si2O7)] (3), K8[(UVIO2)(UVO2)2(Si8O22)] (4), and Cs6[UIV(UVO)2(Si12O32)] (5), were synthesized using different metal halide salt and feeding U/Si ratios. Crystal structure analysis reveals that the utilization of argon atmosphere that helps to avoid possible oxidation of low-valence uranium generates a variety of oxidation states of uranium including U(VI), U(V), U(IV), mixed-valence U(V) and U(VI), and mixed-valence U(IV) and U(V). Characterization of physicochemical properties of representative compounds shows that all these uranium silicate compounds have bandgaps among the range of 2.0-3.4 eV, and mixed-valence uranium silicate compounds have relatively narrower bandgaps. Density functional theory calculations on formation enthalpies, lattice energies, and bandgaps of all five compounds were also performed to provide more structural information about these uranium silicates. This work enriches the library of variable-valence uranium silicate compounds and provides a feasible way to produce novel actinide compounds with intriguing properties through the flux growth method that might show potential application in relevant fields such as storage media for nuclear waste.

2.
BMC Musculoskelet Disord ; 25(1): 359, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38711079

RESUMO

BACKGROUND: With the increasing incidence of steroid-induced necrosis of the femoral head (SNFH), numerous scholars have investigated its pathogenesis. Current evidence suggests that the imbalance between lipogenesis and osteoblast differentiation in bone marrow mesenchymal stem cells (BMSCs) is a key pathological feature of SNFH. MicroRNAs (miRNAs) have strong gene regulatory effects and can influence the direction of cell differentiation. N6-methyladenosine (m6A) is a prevalent epigenetic modification involved in diverse pathophysiological processes. However, knowledge of how miRNAs regulate m6A-related factors that affect BMSC differentiation is limited. OBJECTIVE: We aimed to investigate the role of miR27a in regulating the expression of YTHDF2 in BMSCs. METHODS: We compared miR27a, YTHDF2, and total m6A mRNA levels in SNFH-affected and control BMSCs. CCK-8 and TUNEL assays were used to assess BMSC proliferation and apoptosis. Western blotting and qRT‒PCR were used to measure the expression of osteogenic (ALP, RUNX2, and OCN) and lipogenic (PPARγ and C/EBPα) markers. Alizarin Red and Oil Red O staining were used to quantify osteogenic and lipogenic differentiation, respectively. miR27a was knocked down or overexpressed to evaluate its impact on BMSC differentiation and its relationship with YTHDF2. Bioinformatics analyses identified YTHDF2 as a differentially expressed gene in SNFH (ROC analysis) and revealed potential signaling pathways through GSEA. The effects of YTHDF2 silencing on the lipogenic and osteogenic functions of BMSCs were assessed. RESULTS: miR27a downregulation and YTHDF2 upregulation were observed in the SNFH BMSCs. miR27a knockdown/overexpression modulated YTHDF2 expression, impacting BMSC differentiation. miR27a silencing decreased m6A methylation and promoted osteogenic differentiation, while YTHDF2 silencing exerted similar effects. GSEA suggested potential signaling pathways associated with YTHDF2 in SNFH. CONCLUSION: miR27a regulates BMSC differentiation through YTHDF2, affecting m6A methylation and promoting osteogenesis. This finding suggests a potential therapeutic target for SNFH.


Assuntos
Adenosina/análogos & derivados , Diferenciação Celular , Células-Tronco Mesenquimais , MicroRNAs , Osteogênese , Proteínas de Ligação a RNA , MicroRNAs/genética , MicroRNAs/metabolismo , Células-Tronco Mesenquimais/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Osteogênese/genética , Humanos , Necrose da Cabeça do Fêmur/genética , Necrose da Cabeça do Fêmur/metabolismo , Necrose da Cabeça do Fêmur/induzido quimicamente , Células Cultivadas , Apoptose , Adenosina/metabolismo , Animais , Masculino , Metilação , Proliferação de Células , Lipogênese/genética
3.
BMC Plant Biol ; 23(1): 641, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38082382

RESUMO

BACKGROUND: Trehalose-6-phosphate phosphatase (TPP) is an essential enzyme catalyzing trehalose synthesis, an important regulatory factor for plant development and stress response in higher plants. However, the TPP gene family in soybean has not been reported. RESULTS: A comprehensive analysis of the TPP gene family identified 18 GmTPPs classified into eight groups based on the phylogenetic relationships and the conservation of protein in six monocot and eudicot plants. The closely linked subfamilies had similar motifs and intron/exon numbers. Segmental duplication was the main driving force of soybean GmTPPs expansion. In addition, analysis of the cis-regulatory elements and promoter regions of GmTPPs revealed that GmTPPs regulated the response to several abiotic stresses. Moreover, RNA-seq and qRT-PCR analysis of the tissue-specific GmTPPs under different abiotic stresses revealed that most GmTPPs were associated with response to different stresses, including cold, drought, saline-alkali, and exogenous trehalose. Notably, exogenous trehalose treatment up-regulated the expression of most TPP genes under saline-alkali conditions while increasing the carbohydrate and trehalose levels and reducing reactive oxygen species (ROS) accumulation in soybean sprouts, especially in the saline-alkali tolerant genotype. Furthermore, the interaction network and miRNA target prediction revealed that GmTPPs interacted with abiotic stress response-related transcription factors. CONCLUSIONS: The findings in this study lay a foundation for further functional studies on TPP-based breeding to improve soybean development and stress tolerance.


Assuntos
Glycine max , Trealose , Trealose/metabolismo , Glycine max/genética , Transcriptoma , Filogenia , Melhoramento Vegetal , Estresse Fisiológico/genética , Álcalis , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
4.
Inorg Chem ; 62(38): 15346-15351, 2023 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-37682658

RESUMO

Its high coordination number and tendency to cluster make Th4+ suitable for constructing metal-organic frameworks (MOFs) with novel topologies. In this work, two novel thorium-based heterometallic MOF isomers (IHEP-17 and IHEP-18) were assembled from a Th6 cluster, a multifunctional organic ligand [4-(1H-pyrazol-4-yl)benzoic acid (HPyba)], and Cu2+/Ni2+ cations via the one-pot solvothermal synthesis strategy. The framework features a 6,12-connected new topology net and contains two kinds of supramolecular cage structures, Th36M4 and Th24M2, suitable for guest exchange. Both MOF materials can efficiently adsorb I2. X-ray photoelectron spectroscopy, Raman spectroscopy, and single-crystal X-ray diffraction indicate that the adsorbed iodine is uniformly distributed within the Th36M4 cage but not the Th24M2 cage in the form of I3-.

5.
J Cogn Neurosci ; 31(7): 1018-1029, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30938590

RESUMO

Reading relies on the rapid visual recognition of words viewed in a wide variety of fonts. We used fMRI to identify neural populations showing reduced fMRI responses to repeated words displayed in different fonts ("font-invariant" repetition suppression). We also identified neural populations showing greater fMRI responses to words repeated in a changing font as compared with words repeated in the same font ("font-sensitive" release from repetition suppression). We observed font-invariant repetition suppression in two anatomically distinct regions of the left occipitotemporal cortex (OT), a "visual word form area" in mid-fusiform cortex, and a more posterior region in the middle occipital gyrus. In contrast, bilateral shape-selective lateral occipital cortex and posterior fusiform showed considerable sensitivity to font changes during the viewing of repeated words. Although the visual word form area and the left middle occipital gyrus showed some evidence of font sensitivity, both regions showed a relatively greater degree of font invariance than font sensitivity. Our results show that the neural mechanisms in the left OT involved in font-invariant word recognition are anatomically distinct from those sensitive to font-related shape changes. We conclude that font-invariant representation of visual word form is instantiated at multiple levels by anatomically distinct neural mechanisms within the left OT.


Assuntos
Lobo Occipital/fisiologia , Reconhecimento Visual de Modelos/fisiologia , Leitura , Lobo Temporal/fisiologia , Adulto , Mapeamento Encefálico , Feminino , Lateralidade Funcional , Humanos , Imageamento por Ressonância Magnética , Masculino , Vias Neurais/fisiologia , Adulto Jovem
6.
Int J Cancer ; 144(9): 2266-2278, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30515783

RESUMO

Patients with anaplastic thyroid cancer (ATC) have an extremely poor prognosis despite multimodal therapy with surgery and chemoradiation. Lenvatinib, a multi-targeted tyrosine kinase inhibitor, as well as checkpoint inhibitors targeting the programmed cell death pathway, have proven effective in some patients with advanced thyroid cancer. Combination of these therapies is a potential means to boost effectiveness and minimize treatment resistance in ATC. We utilized our novel immunocompetent murine model of orthotopic ATC to demonstrate that lenvatinib led to significant tumor shrinkage and increased survival, while combination therapy led to dramatic improvements in both. Lenvatinib monotherapy increased tumor-infiltrating macrophages, CD8+ T-cells, regulatory T-cells, and most notably, polymorphonuclear myeloid derived suppressor cells (PMN-MDSCs). While both combination therapies led to further increases in CD8+ T-cells, only the lenvatinib and anti-PD-1 combination decreased PMN-MDSCs. PMN-MDSC expansion was also seen in the blood of mice and one patient receiving lenvatinib therapy for ATC. RNA-Seq of the ATC cell line used in our mouse model demonstrated that lenvatinib has multifaceted effects on angiogenesis, response to hypoxia, the epithelial-to-mesenchymal transition, and on multiple pathways implicated in inflammation and host immunity. Combination of lenvatinib with anti-Gr-1 antibody ameliorated lenvatinib's expansion of MDSCs and significantly improved lenvatinib's anti-tumor effect. These data suggest that MDSCs play a negative role in ATC's response to lenvatinib and support future study of their role as a potential biomarker and treatment target.


Assuntos
Antineoplásicos/farmacologia , Antígeno B7-H1/antagonistas & inibidores , Compostos de Fenilureia/farmacologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Quinolinas/farmacologia , Carcinoma Anaplásico da Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Microambiente Tumoral/imunologia , Animais , Linfócitos T CD8-Positivos/citologia , Linhagem Celular Tumoral , Proliferação de Células , Transição Epitelial-Mesenquimal , Feminino , Humanos , Camundongos , Células Supressoras Mieloides/citologia , Linfócitos T Reguladores/citologia , Carcinoma Anaplásico da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia
7.
Br J Cancer ; 119(10): 1223-1232, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30327563

RESUMO

BACKGROUND: Patients with anaplastic thyroid cancer (ATC) have an extremely poor prognosis despite aggressive multimodal therapy. ATC has a high prevalence of BRAFV600E mutations and is associated with an immunosuppressive microenvironment; we previously demonstrated that the combination of BRAF inhibitor and checkpoint inhibitor immunotherapy synergistically reduce tumour volume in an immunocompetent mouse model of orthotopic ATC. METHODS: We again utilised our mouse model of ATC to assess the combination of BRAFV600E inhibitor PLX4720 and anti-PD-L1 or anti-PD-1 antibody on survival, and performed immune cell profiling of lymphoid and myeloid-lineage cells during maximal treatment response and tumour regrowth. RESULTS: Combination therapy dramatically improved mouse survival. Maximal tumour reduction was associated with increases in the number and cytotoxicity of CD8+ T cells and NK cells, as well as increases in mostly M1-polarised tumour-associated macrophages (TAM) and decreases in myeloid-derived suppressor-like cells. Regrowth of tumour occurred after 2-3 weeks of ongoing combination therapy, and was most significantly associated with decreased TAMs and a dramatic increase in M2-polarisation. CONCLUSIONS: Combination of PLX4720 and anti-PD-L1/PD-1 antibody dramatically reduced tumour volume, prolonged survival and improved the anti-tumour immune profile in murine ATC. Tumour growth inevitably recurred and demonstrated re-emergence of an immunosuppressive tumour microenvironment.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antígeno B7-H1/imunologia , Indóis/uso terapêutico , Receptor de Morte Celular Programada 1/imunologia , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Sulfonamidas/uso terapêutico , Carcinoma Anaplásico da Tireoide/tratamento farmacológico , Carcinoma Anaplásico da Tireoide/imunologia , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/imunologia , Animais , Anticorpos Monoclonais/imunologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Citometria de Fluxo , Imunocompetência , Indóis/imunologia , Camundongos , Sulfonamidas/imunologia , Taxa de Sobrevida , Linfócitos T Citotóxicos/imunologia , Linfócitos T Reguladores/imunologia , Microambiente Tumoral/imunologia , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Appl Opt ; 57(31): 9432-9438, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30461989

RESUMO

A high-efficiency full-duplex radio-over-fiber (RoF) system incorporating time- and wavelength-division multiplexing technology is proposed in this paper, which is more flexible for the wavelength assignment based on an additional subcentral station (SCS). The periodic power fading effect resulting from a radio frequency signal transmitted over an optical fiber is effectively eliminated for the downlink and uplink. Colorless base stations are achieved by a centralized allocation strategy of upstream light sources. At the SCS, an optical cross-connect unit is employed to enhance the utilization of light sources and the flexibility of the proposed RoF system. Simultaneously, the requirements of high-bandwidth modulators and photodetectors are significantly reduced with a centralized optical carrier suppressed modulation and an all-optical frequency downconversion at the SCS. On the basis of the additional SCS, a 26 GHz full-duplex experiment system is demonstrated, and two 1.25 Gbps baseband data signals for downlink and uplink are successfully transmitted over a 40 km standard single-mode fiber.

9.
Soft Matter ; 13(3): 619-626, 2017 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-27991643

RESUMO

Soft solids such as PDMS or silicone are widely needed in many advanced applications such as flexible electronics and medical engineering. The ability to control the structure and properties of the surface of soft solids provides new opportunities in these applications. In particular, mechanical loading induced elastic instability is a convenient method to control the surface morphology. The critical strain at which the crease nucleates is experimentally measured under plane strain conditions, and is found to be consistent with that predicted by nonlinear large deformation theory of creases. Under compressive loading, we find that silicone undergoes a transition of creasing pattern from a single channeling or double channeling crease to an unchanneling crease, depending on the specimen's width and height. Finite element simulations are performed to better understand the underlying mechanism of creasing, wherein a relationship between the depth and spacing of the creases is established. It is found to be in good agreement with the experimental data obtained.

10.
Soft Matter ; 13(35): 6011-6020, 2017 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-28782771

RESUMO

Controlling the morphologies and properties of the surface and/or interface of bimaterials consisting of soft polymers provides new opportunities in many engineering applications. Crease is a widely observed deformation mode in nature and engineering applications for soft polymers where the smooth surface folds into a region of self-contact with a sharp tip, usually induced by the instability from mechanical compression or swelling. In this work, we explore the competition mechanisms between surface and interface creases through numerical simulations and experimental studies on bilayer hydrogels. The surface or interface crease of the bilayer hydrogels under swelling is governed by both the modulus ratio (M2/M1) and the height ratio (H2/H1). Through extensive numerical simulations, we find that the interface crease of the bilayer hydrogels can only occur at a moderate modulus ratio (24 < M2/M1 < 96) and a large height ratio (H2/H1 ≥ 8). Guided by this phase diagram, our experiments confirm that both surface and interface creases can be generated by swelling triggered instability, and the transition of surface to interface creases occurs at the critical value of the height ratio (H2/H1) between 5 and 10. Such an observation is in good agreement with our numerical predictions. Fundamental understandings on the switching between the surface and interface creases provide new insights into the design of highly tunable soft materials and devices over a wide range of length scales.

11.
J Vis ; 17(2): 8, 2017 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-28245488

RESUMO

Stable object perception relies on persistent yet temporary neural representations under constantly fluctuating stimulus conditions. The mechanisms by which such representations are formed and maintained are not fully understood but presumably involve interplay between early and higher tier visual cortical mechanisms. Some neurophysiological models of feature binding in early visual cortex predict persistent contour perception under certain stimulus conditions. Here we show that the duration of contour persistence reflects the persistent operation of visual mechanisms sensitive to contour smoothness, which also influences contour visibility more generally under highly camouflaging stimulus conditions. We distinguish the effect of contour smoothness on contour persistence from observer bias, which also contributes to the surprisingly long duration of contour persistence. We conclude that the strong modulatory effects of contour smoothness on persistence are due to the sustained reverberation of local and global contour-binding mechanisms in visual cortex, which form an important basis of perceptual continuity and stable object perception.


Assuntos
Percepção de Forma/fisiologia , Córtex Visual/fisiologia , Percepção Visual/fisiologia , Adulto , Viés , Feminino , Humanos , Masculino , Variações Dependentes do Observador , Estimulação Luminosa , Adulto Jovem
12.
Cognition ; 242: 105648, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37897882

RESUMO

The target template contains information in memory that is used to guide attention during visual search and is typically thought of as containing features of the actual target object. However, when targets are hard to find, it is advantageous to use other information in the visual environment that is predictive of the target's location to help guide attention. The purpose of these studies was to test if newly learned associations between face and scene category images lead observers to use scene information as a proxy for the face target. Our results showed that scene information was used as a proxy for the target to guide attention but only when the target face was difficult to discriminate from the distractor face; when the faces were easy to distinguish, attention was no longer guided by the scene unless the scene was presented earlier. The results suggest that attention is flexibly guided by both target features as well as features of objects that are predictive of the target location. The degree to which each contributes to guiding attention depends on the efficiency with which that information can be used to decode the location of the target in the current moment. The results contribute to the view that attentional guidance is highly flexible in its use of information to rapidly locate the target.


Assuntos
Atenção , Aprendizagem , Humanos , Sinais (Psicologia) , Percepção Visual
13.
Front Public Health ; 12: 1342632, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39050613

RESUMO

Introduction: The procurement of medicines via China's national volume-based procurement (NVBP) necessitates collaboration among various entities. This paper highlights the legal significance of the engagement of pharmaceutical companies, hospitals, and the National Healthcare Security Administration (NHSA) in improving drug accessibility. Methods: We conducted a numerical simulation using MATLAB to develop an evolutionary game model involving these three participants in NVBP. Results: Our findings indicate that the final evolutionary stabilization strategies are pharmaceutical companies actively participating, hospitals using bid-winning medicines, and the NHSA implementing a low-intensity intervention. The study reveals that the evolutionary outcomes for hospitals and pharmaceutical companies are significantly affected by factors such as NHSA's subsidy level and pharmaceutical companies' level of participation. However, NHSA's decision-making process is less influenced by these factors. Discussion: From a legal perspective, the successful implementation of NVBP, ensuring fairness and legality, requires adherence to relevant policies and regulations. The NHSA should employ statutory incentives and regulatory methods in formulating and adjusting NVBP policy to enable pharmaceutical companies, hospitals, and the NHSA to exercise their rights rationally within the legal framework of the game process.


Assuntos
Indústria Farmacêutica , China , Humanos , Acessibilidade aos Serviços de Saúde , Hospitais
14.
Huan Jing Ke Xue ; 45(3): 1304-1314, 2024 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-38471847

RESUMO

Exploring the nonlinear effect of urbanization on PM2.5 concentration and its driving mechanism is crucial for controlling urban air pollution. Based on remote sensing data and statistical data from 2002 to 2020, spatial autocorrelation, systematic dynamic panel regression, and spatio-temporal geographical weighted regression models were used to analyze the spatio-temporal evolution of PM2.5 concentration in the urban agglomeration of the middle reaches of the Yangtze River and explore the driving mechanism of urbanization on PM2.5 concentration at different spatial scales. The results showed that:① PM2.5 concentration in the middle reaches of the Yangtze River showed an overall decreasing trend from 2002 to 2020, with a spatial distribution pattern of "high in the north and low in the south." ② Hot spot cities expanded towards the western part of the urban agglomeration, whereas cold spot cities showed enhanced spatial correlation. ③ The relationship between PM2.5 concentration and economic, land, and population urbanization followed N-shaped, U-shaped, and U-shaped curves, respectively. Secondary industry and energy consumption significantly promoted the change in PM2.5 concentration, and precipitation and vegetation helped mitigate PM2.5 pollution. ④ The overall driving effects of all urbanization factors in local areas were transformed, and the main areas of influence were concentrated in the southeast, northwest, and southwest of the study area. Considering the current urban development status and regional characteristics of the urban agglomeration in the middle reaches of the Yangtze River, promoting green industrial transformation, rational planning of urban spatial distribution and population distribution, and enhancing infrastructure construction will facilitate the coordinated development between urbanization and environmental protection.

15.
Brain Cogn ; 82(3): 291-300, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23774678

RESUMO

Decision-making consists of several stages of information processing, including an anticipation stage and an outcome evaluation stage. Previous studies showed that the ventral striatum (VS) is pivotal to both stages, bridging motivation and action, and it works in concert with the ventral medial prefrontal cortex (vmPFC) and the amygdala. However, evidence concerning how the VS works together with the vmPFC and the amygdala came mainly from neuropathology and animal studies; little is known about the dynamics of this network in the functioning human brain. Here we used fMRI combined with dynamic causal modeling (DCM) to investigate the information flow along amygdalostriatal and corticostriatal pathways in a facial attractiveness guessing task. Specifically, we asked participants to guess whether a blurred photo of female face was attractive and to wait for a few seconds ("anticipation stage") until an unblurred photo of feedback face, which was either attractive or unattractive, was presented ("outcome evaluation stage"). At the anticipation stage, the bilateral amygdala and VS showed higher activation for the "attractive" than for the "unattractive" guess. At the outcome evaluation stage, the vmPFC and the bilateral VS were more activated by feedback faces whose attractiveness was congruent with the initial guess than by incongruent faces; however, this effect was only significant for attractive faces, not for unattractive ones. DCM showed that at the anticipation stage, the choice-related information entered the amygdalostriatal pathway through the amygdala and was projected to the VS. At the evaluation stage, the outcome-related information entered the corticostriatal pathway through the vmPFC. Bidirectional connectivities existed between the vmPFC and VS, with the VS-to-vmPFC connectivity weakened by unattractive faces. These findings advanced our understanding of the reward circuitry by demonstrating the pattern of information flow along the amygdalostriatal and corticostriatal pathways at different stages of decision-making.


Assuntos
Tonsila do Cerebelo/fisiologia , Gânglios da Base/fisiologia , Tomada de Decisões/fisiologia , Córtex Pré-Frontal/fisiologia , Adolescente , Face , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Vias Neurais , Adulto Jovem
16.
Int J Med Sci ; 10(11): 1485-96, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24046522

RESUMO

Cadmium and its compounds are well-known human carcinogens, but the mechanisms underlying the carcinogenesis are not entirely understood. Our study was designed to elucidate the mechanisms of DNA damage in cadmium-induced malignant transformation of human bronchial epithelial cells. We analyzed cell cycle, apoptosis, DNA damage, gene expression, genomic instability, and the sequence of exons in DNA repair genes in several kinds of cells. These cells consisted of untreated control cells, cells in the fifth, 15th, and 35th passage of cadmium-treated cells, and tumorigenic cells from nude mice using flow cytometry, Hoechst 33258 staining, comet assay, quantitative real-time polymerase chain reaction (PCR), Western blot analysis, random amplified polymorphic DNA (RAPD)-PCR, and sequence analysis. We observed a progressive increase in cell population of the G0/G1 phase of the cell cycle and the rate of apoptosis, DNA damage, and cadmium-induced apoptotic morphological changes in cerebral cortical neurons during malignant transformation. Gene expression analysis revealed increased expression of cell proliferation (PCNA), cell cycle (CyclinD1), pro-apoptotic activity (Bax), and DNA damage of the checkpoint genes ATM, ATR, Chk1, Chk2, Cdc25A. Decreased expression of the anti-apoptotic gene Bcl-2 and the DNA repair genes hMSH2, hMLH1, ERCC1, ERCC2, and hOGG1 was observed. RAPD-PCR revealed genomic instability in cadmium-exposed cells, and sequence analysis showed mutation of exons in hMSH2, ERCC1, XRCC1, and hOGG1 in tumorigenic cells. This study suggests that Cadmium can increase cell apoptosis and DNA damage, decrease DNA repair capacity, and cause mutations, and genomic instability leading to malignant transformation. This process could be a viable mechanism for cadmium-induced cancers.


Assuntos
Apoptose/efeitos dos fármacos , Cádmio/toxicidade , Dano ao DNA/efeitos dos fármacos , Instabilidade Genômica/efeitos dos fármacos , Animais , Brônquios/citologia , Transformação Celular Neoplásica/efeitos dos fármacos , Transformação Celular Neoplásica/genética , Reparo do DNA/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Humanos , Camundongos
17.
Zhonghua Nan Ke Xue ; 19(11): 1034-8, 2013 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-24341101

RESUMO

OBJECTIVE: To investigate the clinical efficacy of Shuganyiyang Capsule combined with conventional Western medicine (tamsulosin hydrochloride sustained release tablets + prostat tablets) for the treatment of type III prostatitis complicated by erectile dysfunction (ED). METHODS: Eighty patients with type III prostatitis complicated by ED were equally randomized to an experimental and a control group, the former treated with Shuganyiyang Capsule combined with tamsulosin hydrochloride sustained release tablets and prostat tablets, while the latter with tamsulosin hydrochloride and prostat only, both for 8 weeks. Then the prostatitis symptoms, erectile function and psychological conditions of the patients were evaluated using NIH-CPSI, IIEF-5, and hospital anxiety and depression scale (HADA and HADD) respectively. The rates of recovery, excellence, effectiveness and ineffectiveness were calculated. RESULTS: The scores on NIH-CPSI, IIEF-5, HADA and HADD obtained at 4 and 8 weeks after treatment showed statistically significant differences between the two time points as well as from the baseline (P < 0.01). At 8 weeks, the scores on NIH-CPSI, IIEF-5, HADA and HADD were 6.83 +/- 4.96, 21.03 +/- 2.54, 6.05 +/- 1.62, and 5.35 +/- 3.30 in the experimental group, as compared with 7.55 +/- 4.89, 17.68 +/- 4.15, 6.88 +/- 2.45, and 7.85 +/- 3.77 in the control (P < 0.05). The rate of effectiveness was significantly higher in the experimental than in the control group (90% [36/40] vs 70% [28/40], P < 0.05). CONCLUSION: Shuganyiyang Capsule combined with conventional Western medicine, such as alpha blockers and galenica, produces definite effect on chronic prostatitis complicated by ED, improves the psychological conditions of the patient, and enhances the therapeutic efficiency of chronic prostatits.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Disfunção Erétil/tratamento farmacológico , Fitoterapia , Prostatite/tratamento farmacológico , Cápsulas , Disfunção Erétil/complicações , Humanos , Masculino , Prostatite/complicações , Sulfonamidas/uso terapêutico , Tansulosina , Resultado do Tratamento
18.
Trends Cogn Sci ; 27(4): 391-403, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36841692

RESUMO

Theories of attention posit that attentional guidance operates on information held in a target template within memory. The template is often thought to contain veridical target features, akin to a photograph, and to guide attention to objects that match the exact target features. However, recent evidence suggests that attentional guidance is highly flexible and often guided by non-veridical features, a subset of features, or only associated features. We integrate these findings and propose that attentional guidance maximizes search efficiency based on a 'good-enough' principle to rapidly localize candidate target objects. Candidates are then serially interrogated to make target-match decisions using more precise information. We suggest that good-enough guidance optimizes the speed-accuracy-effort trade-offs inherent in each stage of visual search.


Assuntos
Memória de Curto Prazo , Percepção Visual , Humanos
19.
Qual Life Res ; 21(3): 495-503, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21695594

RESUMO

BACKGROUND: Rural-urban female migrant workers living in factories are a special majority group in the city of Shenzhen, China. These female workers came from different provinces of mainland China. The health-related issues and quality of life (QOL) of this migrator have become serious public health and social problems, which have not been well characterized. This study aimed to explore the QOL and related factors of rural-urban female migrant workers living in factories in China. METHODS: In total, 3,622 rural-urban female migrant workers completed the Health Survey Short Form (SF-36). Sociodemographic characteristics, health status and job satisfaction during the past 6 months were also collected. RESULTS: Subjects had an average of 2.53 ± 1.93 (median = 2.00, quartile interval = 3.00) diseases. The two-week Morbidity Rate was 21.9%, and only 14.0% of the subjects were satisfied with their current job. Compared to Chinese female norms, the participants scored lower in seven concepts domains of SF-36 (role physical, bodily pain, general health, vitality, social functioning, role-emotional and mental health). Multiple stepwise linear regression analysis showed that after adjustment for age, education level, work duration and job satisfaction, two-week Morbidity Rate, anemia symptoms and muscular soreness proved to be significant predictors for all the 7 domains (except for physical functioning). Digestive system disease was a significant predictor in 5 out of 7 domains, while urinary system disease and gynecological disease were significant predictors in 4 out of 7 domains. CONCLUSIONS: In general, QOL in rural-urban female migrant workers was lower than Chinese female norms. Improving their job satisfaction and controlling job-related disease appears to be critical to improving their QOL.


Assuntos
Qualidade de Vida , Inquéritos e Questionários , Migrantes , Adolescente , Adulto , China , Estudos Transversais , Feminino , Indicadores Básicos de Saúde , Humanos , Entrevistas como Assunto , Satisfação no Emprego , Modelos Lineares , População Rural , Fatores Socioeconômicos , População Urbana
20.
Sci Rep ; 12(1): 21051, 2022 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-36473889

RESUMO

Steroid induced osteonecrosis of the femoral head (ONFH) frequently leads to femoral head collapse and subsequent hip arthritis. This study aimed to investigate the potential therapeutic mechanism of miR-27a on steroid-induced ONFH. Levels of IL-6, TNF-α, miR-27a, Runx2, PPAR-γ and ApoA5 were first examined in bone marrow tissues from steroid-induced ONFH and controls. Subsequently, we overexpressed or knocked down miR-27a in bone marrow mesenchymal stem cells (BMSCs) and detected cell proliferation, osteogenic differentiation, adipogenic differentiation. In addition, miR-27a mimics and BMSCs were injected into the established steroid-induced ONFH rats, and the osteoprotective effects of both were evaluated. Dual luciferase reporter was used to test the targeting effect of miR-27a-3p and PPARG. miR-27a and Runx2 were lowly expressed in steroid-induced ONFH, PPAR-γ and ApoA5 were highly expressed. Overexpression of miR-27a in BMSCs promoted cell proliferation and osteogenic differentiation, inhibited adipogenic differentiation. Furthermore, increasing miR-27a and BMSCs obviously reduced bone loss in steroid induced ONFH rats. The expressions of Runx2 in BMSCs and steroid-induced ONFH rats was significantly up-regulated, while IL-6, TNF-α, PPAR-γ and ApoA5 were down-regulated with miR-27a overexpression. Additionally, PPARG was the target of miR-27a-3p. The results of the present study reveal a role for miR-27a in promoting osteogenesis and may have a synergistic effect with BMSCs.


Assuntos
Células-Tronco Mesenquimais , MicroRNAs , Ratos , Animais , Osteogênese/genética , Fator de Necrose Tumoral alfa , Cabeça do Fêmur , Interleucina-6/genética , Esteroides/efeitos adversos , MicroRNAs/genética
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