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Of the factors studied in individual ageing, the accumulation of senescent cells has been considered as an essential cause of organ degeneration to eventually initiate age-related diseases. Cellular senescence is attributed to the accumulation of damage for an inducement in the activation of cell cycle inhibitory pathways, resulting the cell permanently withdraw from the cell proliferation cycle. Further, senescent cells will activate the inflammatory factor secretion pathway to promote the development of various age-related diseases. Senolytics, a small molecule compound, can delay disease development and extend mammalian lifespan. The evidence from multiple trials shows that the targeted killing of senescent cells has a significant clinical application for the treatment of age-related diseases. In addition, senolytics are also significant for the development of ageing research in solid organ transplantation, which can fully develop the potential of elderly organs and reduce the age gap between demand and supply. We conclude that the main characteristics of cellular senescence, the anti-ageing drug senolytics in the treatment of chronic diseases and organ transplantation, and the latest clinical progress of related researches in order to provide a theoretical basis for the prevention and treatment of ageing and related diseases.
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Envelhecimento , Senescência Celular , Senoterapia , Humanos , Senescência Celular/efeitos dos fármacos , Senoterapia/farmacologia , Senoterapia/uso terapêutico , Envelhecimento/efeitos dos fármacos , Envelhecimento/metabolismo , Animais , Transplante de ÓrgãosRESUMO
Asherman's syndrome (AS) occurs as a consequence of severe damage to the endometrial basalis, usually leading to menstrual abnormalities, infertility, and recurrent miscarriage in women. Currently, human endometrium-derived adventitial cells (En-ADVs) are considered ideal seed cells with high pluripotency for regenerative medicine. However, critical issues such as noninvasive repair of tissues, targeting of native stem cells, and continuous action in the injured sites are not well resolved. Herein, En-ADV spheroid-loaded hierarchical microneedles (MN/En-ADV) for in situ intrauterine repair are developed. The flexible microneedles are fabricated with gelatin methacryloyl and lactoferrin, imparting the characteristics of rapid degradation and antimicrobial activity. Benefiting from an array of microwells on microneedles, En-ADVs can rapidly form 3D cell spheroids, which display higher potential for cell proliferation, differentiation, and migration than dissociated cells. With the application of MN/En-ADV, the repaired uteri show well-defined myometrial regeneration, angiogenesis, and an increase of endometrial receptivity in a rat AS model. Notably, embryos are able to implant in the reconstructed sites and remain viable, indicating that this system promotes the restoration of both normal morphology and reproductive function in the injured uterus. It is anticipated that multifunctional MN/En-ADV can be an ideal candidate for versatile in situ tissue regeneration.
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Anti-Infecciosos , Ginatresia , Regeneração , Útero , Animais , Anti-Infecciosos/farmacologia , Endométrio/crescimento & desenvolvimento , Feminino , Gelatina , Ginatresia/terapia , Humanos , Metacrilatos , Ratos , Útero/crescimento & desenvolvimentoRESUMO
BACKGROUND: To investigate the potential role of Long Non-coding RNAs (lncRNAs) in the progression of osteosarcoma. METHODS: The candidate lncRNAs were screened with RNA-seq and confirmed with quantitative real-time PCR. Using MTS, transwell assay, and flow cytometric analysis, the effects of overexpressed lnc-SELPLG-2:1 on cell functions were determined. Immunohistochemical staining, fluorescence in situ hybridization, and luciferase reporter assay were used to evaluate the potential mechanism of lnc-SELPLG-2:1 in vivo and in vitro using a tumor model. Moreover, the effects of overexpression of hsa-miR-10a-5p on the functions of SaOS2 cells were determined using functional cell analysis. A response test was used to confirm the mechanism by which lnc-SELPLG-2:1 sponge hsa-miR-10a-5p promotes the expression of BTRC to regulate osteosarcoma. RESULTS: Lnc-SELPLG-2:1 was highly expressed in osteosarcoma compared to normal cells and bone and marrow samples. Inhibition of lnc-SELPLG-2:1 accelerated cell apoptosis and suppressed cell proliferation, migration, and invasion, whereas lnc-SELPLG-2:1 overexpression had the opposite effect. Moreover, inhibiting lnc-SELPLG-2:1 in an in vivo model decreased tumor size and suppressed the expression of cell migration-related proteins. The prediction, dual luciferase assay, and response test results indicated that hsa-miR-10-5p and BTRC were involved in the lnc-SELPLG-2:1 cascade. Unlike lnc-SELPLG-2:1, hsa-hsa-miR-10a-5p had opposite expression and function. Competitive binding of lnc-SELPLG-2:1 to hsa-hsa-miR-10a-5p prevented BTRC from miRNA-mediated degradation, thereby activating the expression of VIM, MMP9, and MMP2, promoting osteosarcoma cell proliferation, migration, and invasion, and inhibiting apoptosis. CONCLUSION: Lnc-SELPLG-2:1 is an oncogenesis activator in osteosarcoma, and its functions are performed via hsa-miR-10a-5p /BTRC cascade.
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Neoplasias Ósseas , MicroRNAs , Osteossarcoma , RNA Longo não Codificante , Neoplasias Ósseas/patologia , Carcinogênese/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Humanos , Hibridização in Situ Fluorescente , Metaloproteinase 2 da Matriz , Metaloproteinase 9 da Matriz , Glicoproteínas de Membrana , MicroRNAs/genética , MicroRNAs/metabolismo , Osteossarcoma/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismoRESUMO
BACKGROUND: Essential proteins have great impacts on cell survival and development, and played important roles in disease analysis and new drug design. However, since it is inefficient and costly to identify essential proteins by using biological experiments, then there is an urgent need for automated and accurate detection methods. In recent years, the recognition of essential proteins in protein interaction networks (PPI) has become a research hotspot, and many computational models for predicting essential proteins have been proposed successively. RESULTS: In order to achieve higher prediction performance, in this paper, a new prediction model called TGSO is proposed. In TGSO, a protein aggregation degree network is constructed first by adopting the node density measurement method for complex networks. And simultaneously, a protein co-expression interactive network is constructed by combining the gene expression information with the network connectivity, and a protein co-localization interaction network is constructed based on the subcellular localization data. And then, through integrating these three kinds of newly constructed networks, a comprehensive protein-protein interaction network will be obtained. Finally, based on the homology information, scores can be calculated out iteratively for different proteins, which can be utilized to estimate the importance of proteins effectively. Moreover, in order to evaluate the identification performance of TGSO, we have compared TGSO with 13 different latest competitive methods based on three kinds of yeast databases. And experimental results show that TGSO can achieve identification accuracies of 94%, 82% and 72% out of the top 1%, 5% and 10% candidate proteins respectively, which are to some degree superior to these state-of-the-art competitive models. CONCLUSIONS: We constructed a comprehensive interactive network based on multi-source data to reduce the noise and errors in the initial PPI, and combined with iterative methods to improve the accuracy of necessary protein prediction, and means that TGSO may be conducive to the future development of essential protein recognition as well.
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Biologia Computacional , Mapas de Interação de Proteínas , Algoritmos , Mapeamento de Interação de Proteínas , Proteínas/genética , Proteínas/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismoRESUMO
Dehydrins, also known as Group II late embryogenesis abundant (LEA) proteins, are classic intrinsically disordered proteins, which have high hydrophilicity. A wide range of hostile environmental conditions including low temperature, drought, and high salinity stimulate dehydrin expression. Numerous studies have furnished evidence for the protective role played by dehydrins in plants exposed to abiotic stress. Furthermore, dehydrins play important roles in seed maturation and plant stress tolerance. Hence, dehydrins might also protect plasma membranes and proteins and stabilize DNA conformations. In the present review, we discuss the regulatory networks of dehydrin gene expression including the abscisic acid (ABA), mitogen-activated protein (MAP) kinase cascade, and Ca2+ signaling pathways. Crosstalk among these molecules and pathways may form a complex, diverse regulatory network, which may be implicated in regulating the same dehydrin.
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Fenômenos Fisiológicos Vegetais , Proteínas de Plantas/metabolismo , Plantas/metabolismo , Ácido Abscísico/metabolismo , Sinalização do Cálcio , Regulação da Expressão Gênica de Plantas , Sistema de Sinalização das MAP Quinases , Estresse FisiológicoRESUMO
Intestinal lymphatic transport has been proved to have contribution to oral absorption of some highly lipophilic drugs. T-OA, 3ßhydroxyolea-12-en-28-oic acid-3,5,6-trimethylpyrazin-2-methylester, has been reported to have anti-cancer activity. Howeverï¼T-OA's poor solubility and difficulty to be absorbed cause low oral bioavailability. This work aims to investigate the influence of T-OA liposomes on intestinal lymphatic transport with rat model. T-OA liposomes were prepared by freeze-drying method, and particle size, zeta potential and entrapment efficiency of T-OA liposomes were detected to evaluate liposomes. Conscious restrained rat model was selected to evaluate intestinal lymphatic transport. The particle size, zeta potential and entrapment efficiency of T-OA liposomes were (184.05 ± 10.93) nm, (-21±0.85) mV and (93.24±2.25) %, respectively. The cumulative amounts in mesenteric lymph of T-OA liposomes and T-OA suspension within 12 h were (921.39±19.73) µg and (332.31±21.39) µg (n=6), respectively. Experimental results showed that T-OA liposomes could significantly promote T-OA's intestinal lymphatic transport and enhance its oral bioavailability.
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Antineoplásicos Fitogênicos/metabolismo , Absorção Intestinal/fisiologia , Vasos Linfáticos/metabolismo , Ácido Oleanólico/metabolismo , Pirazinas/metabolismo , Administração Oral , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Absorção Intestinal/efeitos dos fármacos , Lipossomos , Vasos Linfáticos/efeitos dos fármacos , Masculino , Ácido Oleanólico/química , Ácido Oleanólico/farmacologia , Pirazinas/química , Pirazinas/farmacologia , Ratos , Ratos Sprague-DawleyRESUMO
Decidualization renders the endometrium transiently receptive to an implanting blastocyst although the underlying mechanisms remain incompletely understood. The aim of this study was to determine the role of chemokine CXCL16 and its receptor CXCR6 in the decidualization during pregnancy. Here, the expression of CXCL16 was investigated in endometrial tissues, decidua and placenta in this study. Compared with endometrial tissue, protein expression of CXCL16 was significantly higher in tissues from the fertile control samples, especially in villus. Meanwhile, the primary trophoblast cells and decidual stromal cells (DSCs) secreted more CXCL16 and expressed higher CXCR6 compared to endometrial stromal cells (ESCs) in vitro. Stimulation with the inducer of decidualization (8-bromoadenosine 3',5'-cyclic with medroxyprogesterone acetate, 8-Br-cAMP plus MPA) significantly upregulated the expression of CXCL16 and CXCR6 in ESCs in vitro. After treatment with exogenous recombinant human CXCL16 (rhCXCL16) or trophoblast-secreted CXLC16, decidualised ESCs showed a significant decidual response, mainly characterised by increased prolactin (PRL) secretion. Simultaneously, PI3K/PDK1/AKT/Cyclin D1 pathway in decidualised ESCs were activated by rhCXCL16, and AKT inhibitor GS 690693 abolished the PRL secretion of ESCs that was triggered by rhCXCL16. Finally, the impaired CXCL16/CXCR6 expression could be observed at the maternal-foetal interface from patients who have experienced spontaneous abortion. This study suggests that the CXCL16/CXCR6 axis contributes to the progression of ESC decidualization by activating PI3K/PDK1/AKT/Cyclin D1 pathway. It unveils a new paradigm at the maternal-foetal interface in which CXCL16 is an initiator for the molecular crosstalk that enhances decidualization of ESCs.
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Diferenciação Celular , Quimiocina CXCL16/metabolismo , Decídua/citologia , Endométrio/citologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores CXCR6/metabolismo , Fatores de Transcrição/metabolismo , Adulto , Células Cultivadas , Decídua/metabolismo , Endométrio/metabolismo , Feminino , Humanos , Fosforilação , Gravidez , Primeiro Trimestre da Gravidez , Células Estromais/citologia , Células Estromais/metabolismo , Trofoblastos/citologia , Trofoblastos/metabolismoRESUMO
As Cpf1 cleaves double-stranded DNA in a staggered way, it can be used in DNA assembly. However, the Cpf1 cleavage was found to be inaccurate, which may cause errors in DNA assembly. Here, the Cpf1 cleavage sites were precisely characterized, where the cleavage site on the target strand was around the 22nd base relative to the protospacer adjacent motif site, but the cleavage on the non-target strand was affected by the spacer length. When the spacer length was 20 nt or longer, Cpf1 mainly cleaved around the 14th and the 18th bases on the non-target strand; otherwise, with a shorter spacer (i.e. 17-19 nt), Cpf1 mainly cleaved after the 14th base, generating 8-nt sticky ends. With this finding, Cpf1 with a 17-nt spacer crRNA were employed for in vitro substitution of the actII-orf4 promoter in the actinorhodin biosynthetic cluster with a constitutively expressing promoter. The engineered cluster yielded more actinorhodin and produced actinorhodin from an earlier phase. Moreover, Taq DNA ligase was further employed to increase both the ligation efficiency and the ligation accuracy of the method. We expect this CCTL (Cpf1-assisted Cutting and Taq DNA ligase-mediated Ligation) method can be widely used in in vitro editing of large DNA constructs.
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Proteínas Associadas a CRISPR/metabolismo , DNA/metabolismo , Taq Polimerase/metabolismo , Francisella/enzimologiaRESUMO
BACKGROUND: Hypertension is a major risk factor for the global burden of disease, particularly in countries that are not economically developed. This study aimed to evaluate risk factors associated with self-reported hypertension among residents of Inner Mongolia using a cross-sectional study and to explore trends in the rate of self-reported hypertension. METHODS: Multi-stage stratified cluster sampling was used to survey 13,554 participants aged more than 15 years residing in Inner Mongolia for the 2013 Fifth Health Service Survey. Hypertension was self-reported based on a past diagnosis of hypertension and current use of antihypertensive medication. Adjusted odds risks (ORs) of self-reported hypertension were derived for each independent risk factor including basic socio-demographic and clinical factors using multivariable logistic regression. An optimized risk score model was used to assess the risk and determine the predictive power of risk factors on self-reported hypertension among Inner Mongolia residents. RESULTS: During study period, self-reported hypertension prevalence was 19.0% (2571/13,554). In multivariable analyses, both female and minority groups were estimated to be associated with increased risk of self-reported hypertension, adjusted ORs (95% CI) were 1.22 (1.08, 1.37) and 1.66 (1.29, 2.13) for other minority compared with Han, increased risk of self-reported hypertension prevalence was associated with age, marital status, drinking, BMI, and comorbidity. In the analyses calculated risk score by regression coefficients, old age (≥71) had a score of 12, which was highest among all examined factors. The predicted probability of self-reported hypertension was positively associated with risk score. Of 13,421 participants with complete data, 284 had a risk score greater than 20, which corresponded to a high estimated probability of self-reported hypertension (≥67%). CONCLUSIONS: Self-reported hypertension was largely related to multiple clinical and socio-demographic factors. An optimized risk score model can effectively predict self-reported hypertension. Understanding these factors and assessing the risk score model can help to identify the high-risk groups, especially in areas with multi-ethnic populations.
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Hipertensão/epidemiologia , Adulto , Consumo de Bebidas Alcoólicas/epidemiologia , Anti-Hipertensivos , China/epidemiologia , Estudos Transversais , Feminino , Inquéritos Epidemiológicos , Humanos , Entrevistas como Assunto , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prevalência , Pesquisa Qualitativa , Fatores de Risco , AutorrelatoRESUMO
Accompanied with the internal non-homologous end joining (NHEJ) system, Cas9 can be used to easily inactivate a gene or delete a fragment through introduction of DNA double-stranded breaks (DSBs) in eukaryotic cells. While in most prokaryotes (e.g. Escherichia coli), due to the lack of NHEJ, homologous recombination (HR) is required for repair of DSBs, which is less convenient. Here, a markerless system was developed for rapid gene inactivation or fragment deletion in E. coli via introduction of both Cas9 and a bacterial NHEJ system. Three bacterial NHEJ systems, i.e. Mycobacterium smegmatis (Msm), Mycobacterium tuberculosis (Mtb) and Bacillus subtilis (Bs), were tested in E. coli, and the MsmNHEJ system showed the best efficiency. With the employment of Cas9 and MsmNHEJ, we efficiently mutated lacZ gene, deleted glnALG operon and two large DNA fragments (67 kb and 123 kb) in E. coli, respectively. Moreover, the system was further designed to allow for continuous inactivation of genes or deletion of DNA fragments in E. coli. We envision this system can be extended to other bacteria, especially those with low HR efficiency.
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Sistemas CRISPR-Cas , Reparo do DNA por Junção de Extremidades , DNA Bacteriano/genética , Escherichia coli/genética , Mycobacterium smegmatis/genética , Deleção de Sequência , Bacillus subtilis/genética , Sequência de Bases , Engenharia Genética/métodos , Óperon Lac/genética , Modelos Genéticos , Mutagênese , Mycobacterium tuberculosis/genética , Óperon/genética , Reprodutibilidade dos Testes , Homologia de Sequência do Ácido NucleicoRESUMO
UNLABELLED: Ectoine and hydroxyectoine are excellent compatible solutes for bacteria to deal with environmental osmotic stress and temperature damages. The biosynthesis cluster of ectoine and hydroxyectoine is widespread among microorganisms, and its expression is activated by high salinity and temperature changes. So far, little is known about the mechanism of the regulation of the transcription of ect genes and only two MarR family regulators (EctR1 in methylobacteria and the EctR1-related regulator CosR in Vibrio cholerae) have been found to negatively regulate the expression of ect genes. Here, we characterize GlnR, the global regulator for nitrogen metabolism in actinomycetes, as a negative regulator for the transcription of ectoine/hydroxyectoine biosynthetic genes (ect operon) in Streptomyces coelicolor. The physiological role of this transcriptional repression by GlnR is proposed to protect the intracellular glutamate pool, which acts as a key nitrogen donor for both the nitrogen metabolism and the ectoine/hydroxyectoine biosynthesis. IMPORTANCE: High salinity is deleterious, and cells must evolve sophisticated mechanisms to cope with this osmotic stress. Although production of ectoine and hydroxyectoine is one of the most frequently adopted strategies, the in-depth mechanism of regulation of their biosynthesis is less understood. So far, only two MarR family negative regulators, EctR1 and CosR, have been identified in methylobacteria and Vibrio, respectively. Here, our work demonstrates that GlnR, the global regulator for nitrogen metabolism, is a negative transcriptional regulator for ect genes in Streptomyces coelicolor. Moreover, a close relationship is found between nitrogen metabolism and osmotic resistance, and GlnR-mediated regulation of ect transcription is proposed to protect the intracellular glutamate pool. Meanwhile, the work reveals the multiple roles of GlnR in bacterial physiology.
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Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão Gênica/fisiologia , Pressão Osmótica/fisiologia , Regulon/fisiologia , Streptomyces coelicolor/metabolismo , Transativadores/metabolismo , Transcrição Gênica/fisiologia , Diamino Aminoácidos/biossíntese , Proteínas de Bactérias/genética , Glutamatos/metabolismo , Mutação , Transativadores/genéticaRESUMO
The radiation spectrum from the plasmas contains a large amount of information of plasmas. Thus, one of the most effective methods to detecting the plasma parameters is measure the plasma radiation spectrum. Until now, since the restriction of the Toshiba mechanically ruled aberration-corrected concave gratings, the measurable wavelength range of the incidence flat-field grazing spectrometer in the soft X-ray range are only from 5 to 40 nm. In order to extend the wavelength rang of grazing incidence flat-field spectrometer, first, a grazing incidence concave reflection grating ray-trace code is written using optical path equation. Second, under the same conditions with reference 6, we compare our numerical results with Harada's results. The results show that our results agree very well with the results of Harada. The results of comparison show that our ray-trace code is believable. Finally, the variety of the flat-field curves are detailedly investigated using the ray-trace code with the different grazing incidence conditions. The results show that the measurable wavelength range of the incidence flat-field grazing spectrometer are extended to 5~80 nm from the soft X-ray wavelength range of 5~40 nm. This result theoretically demonstrates the possibility of expanded the traditional band flat-field grazing incidence spectrometer from soft X-ray band to the extreme ultraviolet (XUV), and also bring a new design ideas for improving the use of grazing incidence flat field concave grating.
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Although much effort has been made for studies on aptamer-target interactions due to promising applications of aptamers in biomedical and analytical fields, measurement of the aptamer-target binding constant and binding site still remains challenging. Herein, we report a sensitive label-free chemiluminescence (CL) strategy to determine the target concentration and, more importantly, to measure the target-aptamer binding constant and binding site. This approach is suitable for multiple types of targets, including small molecules, peptides, and proteins that can enhance the CL initiated by N-(aminobutyl)-N-ethylisoluminol functionalized gold colloids, making the present method a general platform to investigate aptamer-target interactions. This approach can achieve extremely high sensitivity with nanogram samples for measuring the target-aptamer binding constant. And the measurement could be rapidly performed using a simple and low-cost CL system. It provides an effective tool for studying the binding of biologically important molecules to nucleic acids and the selection of aptamers. Besides, we have also discovered that the 14-mer aptamer fragment itself split from the ATP-binding aptamer could selectively capture ATP. The binding constant, site, and conformation between ATP and the 14-mer aptamer fragment were obtained using such a novel CL strategy and molecular dynamic simulation.
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Aptâmeros de Nucleotídeos/análise , Medições Luminescentes/métodos , Arginina Vasopressina/química , Sítios de Ligação , Espectroscopia de Ressonância Magnética , Conformação de Ácido Nucleico , Espectrofotometria Ultravioleta , Trombina/químicaRESUMO
This article studied the influence of silica (SiO2) particles on the crosslinked network and the molecular mobility of ethylene-propylene-diene (EPDM) rubber chains by dynamic mechanical analysis (DMA). When SiO2 fraction is lower than 8 phr, the chain segments that participate in the glass-rubber transition (α transition) decrease with increasing the SiO2 content, while the whole crosslinked network is almost unaffected by the presence of SiO2. When the SiO2 fraction increases to about 20 phr, there appears a new tan δ peak (α' transition) above the α transition. This could be because the crosslinking reaction took place only on a small scale and the formed network became gradually incomplete when the content of the particles exceeded some critical value, and the α' transition is attributed primarily to the motion of non-elastic network chains loosely attached to the three-dimensional network. However, at SiO2 loadings higher than 40 phr, the crosslinking density was kept basically constant. The α' transition is hindered by a restriction of the chain mobility due to SiO2. The different changes of α' transition depended on the two coupled effects of SiO2, including restricting the chain mobility and decreasing the crosslinking density. Correspondingly, with increasing the mobility of EPDM chains and SiO2-induced strengthening, the mechanical properties of EPDM composite are dramatically improved. With the addition of 20 phr of SiO2 in the EPDM, a 113% increase in the elongation at break, a 510% increase in the fracture energy, and a 283% increase in the tensile strength are achieved.
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Traditional enterprise management believes that telecommuting activities are out of the enterprise's control, which may reduce staff performance. We use the extension of job demand-resource theory and work embeddedness theory to develop and test the intermediary mechanism of embedded in and out of work in telework. Moreover, it judges the mediating effect of job embeddedness on telecommuting â job performance. With the help of family conflict theory, we have revealed the possible performance changes in telework and the impact of family on telework. We predict embedding outside of work may reduce job performance. However, this worry will not happen under the adjustment of digital leadership and job insecurity. We collected survey data from 36 enterprise teams and 328 members. We have confirmed that work performance will not be reduced by telecommuting. Digital leadership magnifies the embedding of telecommuting resources into employees' work to a certain extent and inhibits the embedding problem outside work caused by telecommuting requirements. The telecommuting requirement may become a positive factor for employees staying home and avoiding workplace conflicts. We confirmed the inhibitory effect of job embeddedness on turnover rate and expanded the antecedent model of job embeddedness theory.
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Introduction: Shared decision making (SDM) is a collaborative process involving both healthcare providers and patients in making medical decisions, which gains increasing prominence in healthcare practice. But evidence on the level of SDM in medical practice and barriers as well as stimulus during the SDM implementation among aesthetic dermatologists is limited in China. Methods: From July to August 2023, 1938 dermatologists were recruited online in China. Data were collected through an electronic questionnaire covering: (1) demographic features; (2) SDM questionnaire physician version (SDM-Q-Doc); and (3) stimulus and barriers in SDM implementation. Logistic regression was applied to explore factors associated with SDM practice, barriers, and stimulus of SDM implementation, respectively. Results: The 1938 dermatologists included 1329 females (68.6%), with an average age of 35 years. The total SDM score ranged from 0 to 45, with a median value of 40 (IQR: 35-44), and the median stimulus score and barriers scores were 28 (IQR: 24-32) and 19 (IQR: 13-26), respectively. The prevalence of good SDM was 27.2%, logistic regression indicated that female dermatologists (odds ratio, OR=1.21, 95% confidence interval, CI: 0.96-1.51), and dermatologists with more years of aesthetic practice had a higher proportion of good SDM practice (OR was 1.44 for 5-9 years, 1.58 for 10-15 years and 1.77 for over 15 years). Moreover, female dermatologists and dermatologists with higher education level and serviced in private settings had lower barrier scores; female dermatologists and dermatologists with more years of aesthetic practice had higher stimulus scores. Conclusion: Chinese aesthetic dermatologists appear to implement SDM at an active level, with more stimulus and less barriers in SDM implementation. The integration of SDM into clinical practice among dermatologists is beneficial both for patients and dermatologists. Moreover, SDM practice should be strongly promoted and enhanced during medical aesthetics, especially among male dermatologists, dermatologists with less working experience, and those who work at public institutions.
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Objective: Shared decision-making (SDM) is a collaborative process in which patients and healthcare providers jointly make a medical decision. This cross-sectional study aimed to identify the implementation status of shared decision-making among dermatologists engaging in medical esthetics in China and to identify factors associated with the good practice of SDM among them. Methods: From January to June 2023, a total of 1,287 dermatologists engaging in medical esthetics in China were recruited and completed the online interviews about their implementation of SDM based on the Shared Decision-Making Questionnaire for Doctors (SDM-Q-Doc). Logistic regression was used to calculate the odds ratio (OR) and 95% confidence interval (CI) to explore factors associated with the higher SDM score achievement among dermatologists with medical esthetic practice. Results: The median value of the total SDM score was 39, and 48% (621/1278) of dermatologists with medical esthetic practice achieved at least 40 out of 45 scores. Logistic regression indicated that dermatologists aged 40-49 or ≥ 50 years and those engaging in medical esthetic practice for ≥5 years were more likely to achieve at least 40 out of 45 scores compared to dermatologists aged <30 years with less than 5 years of medical esthetic practice. The ORs were 1.82 (95% CI: 1.13-3.12), 1.94 (95% CI: 1.13-3.61), and 1.76 (95% CI: 1.34-2.31), respectively. Conclusion: The SDM implementation level among Chinese dermatologists engaging in medical esthetics is high, especially for those who are older age and have more years of practice. Hence, it is highly recommended to promote and enhance SDM practice among younger dermatologists engaging in medical esthetics with less working experience.
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Background and objectives: Education, occupation, and cognitive activity are key indicators of cognitive reserve and are thought to influence cognitive impairment. However, the individual and combined impacts of these factors are not fully understood. This study aims to investigate the roles of education and occupation in cognitive impairment while controlling for brain reserve and cognitive activity. Methods: This cross-sectional study involved 369 participants aged 50 years or older from urban outpatient clinics in Jilin Province, China. Cognitive impairment was assessed using neuropsychological scales and brain imaging. Cognitive activity was evaluated with the Cognitive Reserve Scale (CRS). Covariance analysis and logistic regression models were used to analyze the associations, adjusting for age, sex, education, and occupation. Results: Higher education was significantly associated with a lower risk of cognitive impairment (p < 0.001), regardless of occupation. In contrast, occupational complexity and cognitive activity did not show a significant relationship with cognitive impairment (p > 0.05). Conclusion: Education, rather than occupation or cognitive activities, is a significant predictor of cognitive impairment, highlighting the importance of educational attainment in cognitive health.
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The impact of efferocytosis-related genes (ERGs) on the diagnosis of colorectal cancer (CRC) remains unclear. In this study, efferocytosis-associated biomarkers for the diagnosis of CRC were identified by integrating data from transcriptome sequencing and public databases. Finally, the expression of biomarkers was validated by real-time quantitative polymerase chain reaction (RT-qPCR). Our study may provide a reference for CRC diagnosis. BACKGROUND: It has been shown that some efferocytosis related genes (ERGs) are associated with the development of cancer. However, it is still uncertain how ERGs may influence the diagnosis of colorectal cancer (CRC). METHODS: In our study, the CRC cohorts were gained from transcriptome sequencing and the gene expression omnibus (GEO) database (GSE71187). Efferocytosis related biomarkers with diagnostic utility for CRC were identified through combining differentially expressed analysis, machine learning algorithms, and receiver operating characteristic (ROC) analysis. Then, infiltration abundance of immune cells between CRC and control was evaluated. The regulatory networks (including mRNA-miRNA-lncRNA and miRNA/transcription factors (TF)-mRNA networks) were created. Finally, the expression of biomarkers was validated via real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: There were 3 biomarkers (ELMO3, P2RY12, and PDK4) related diagnosis for CRC patients gained. ELMO3 was highly expressed in CRC group, while P2RY12 and PDK4 was lowly expressed. Besides, the infiltrating abundance of 3 immune cells between CRC and control groups was significantly differential, namely activated CD4 memory T cells, macrophages M0, and resting mast cells. We then constructed a mRNA-miRNA-lncRNA network containing 3 mRNAs, 33 miRNAs, and 22 lncRNAs, and a miRNA/TF-mRNA network including 3 mRNAs, 33 miRNAs, and 7 TFs. Additionally, RT-qPCR results revealed that the expression trends of all biomarkers were consistent with the transcriptome sequencing data and GSE71187. CONCLUSION: Taken together, this study provides three efferocytosis related biomarkers (ELMO3, P2RY12, and PDK4) for diagnosis of CRC, providing a scientific reference for further studies of CRC.
Assuntos
Biomarcadores Tumorais , Neoplasias Colorretais , Eferocitose , Humanos , Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Eferocitose/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , MicroRNAs/genética , TranscriptomaRESUMO
BACKGROUND: Intrauterine adhesions (IUAs) jeopardise uterine function in women, which is a great challenge in the clinic. Previous studies have shown that endometrial perivascular cells (En-PSCs) can improve the healing of scarred uteri and that hydroxysafflor yellow A (HSYA) promotes angiogenesis. The purpose of this study was to observe whether the combination of En-PSCs with HSYA could improve the blood supply and fertility in the rat uterus after full-thickness injury. METHODS: En-PSCs were sorted by flow cytometry, and the effect of HSYA on the proliferation and angiogenesis of the En-PSCs was detected using CCK-8 and tube formation assays. Based on a previously reported rat IUA model, the rat uteri were sham-operated, spontaneously regenerated, or treated with collagen-loaded PBS, collagen-loaded HSYA, collagen-loaded En-PSCs, or collagen-loaded En-PSCs with HSYA, and then collected at both 30 and 90 days postsurgery. HE staining and Masson staining were used to evaluate uterine structure and collagen fibre deposition, and immunohistochemical staining for α-SMA and vWF was used to evaluate myometrial regeneration and neovascularization in each group. A fertility assay was performed to detect the recovery of pregnancy function in each group. RNA-seq was performed to determine the potential mechanism underlying En-PSCs/HSYA treatment. Immunofluorescence, tube formation assays, and Western blot were used to validate the molecular mechanism involved. RESULTS: The transplantation of Collagen/En-PSCs/HSYA markedly promoted uterine repair in rats with full-thickness injury by reducing fibrosis, increasing endometrial thickness, regenerating myometrium, promoting angiogenesis, and facilitated live births. RNA sequencing results suggested that En-PSCs/HSYA activated the NRG1/ErbB4 signaling pathway. In vitro tube formation experiments revealed that the addition of an ErbB inhibitor diminished the tube formation ability of cocultured En-PSCs and HUVECs. Western blot results further showed that elevated levels of NRG1 and ErbB4 proteins were detected in the Collagen/En-PSCs/HSYA group compared to the Collagen/En-PSCs group. These collective results suggested that the beneficial effects of the transplantation of Collagen/En-PSCs/HSYA might be attributed to the modulation of the NRG1/ErbB4 signaling pathway. CONCLUSIONS: The combination of En-PSCs/HSYA facilitated morphological and functional repair in rats with full-thickness uterine injury and may promote endometrial angiogenesis by regulating the NRG1/ErbB4 signaling pathway.