Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.635
Filtrar
1.
Artigo em Inglês | MEDLINE | ID: mdl-36707420

RESUMO

The Chinese hamster ovary (CHO) cell is the most widely used biopharmaceutical expression system, but its long-term expression is unstable. This issue can be effectively addressed by site-specific integration of exogenous genes into the genome. Therefore, exogenous protein sites with stable expression in the CHO cell genome must be identified. CRISPR/Cas9 technology was used in this study to integrate various exogenous genes into the ScltI site as a "hot spot" at the CHO-K1 cell genome NW_003614095.1, and the stability and adaptability of exogenous genes expressed at the site were investigated. Flow cytometry sorting technology was used to obtain positive monoclonal cell lines that expressed either intracellular protein green fluorescent protein (EGFP) or secretory protein human serum albumin (HSA). For 60 passages, the positive monoclonal cell lines' cell growth cycles and exogenous protein expression were both observed. The results demonstrated that integrating the gene encoding exogenous proteins into the ScltI site had no effect on cell growth. The fluorescence intensity of EGFP was similar after 60 passages, and the expression of HSA increased slightly. Additionally, the super-monomeric protein VWF hydrolase (ADAMTS13) (190 kDa), human coagulation factor VII (FVII) (55 kDa), and interferon α2b (12 kDa) were integrated into the ScltI site for expression. In conclusion, the site located in the first exon of the ScltI gene within the CHO-K1 cell genome NW_003614095.1 is an ideal "hot spot" for the stable expression of various exogenous proteins. KEY POINTS: • The site-specific integration strategy of an exogenous gene in CHO cells was established for the ScltI site. • The genes for EGFP and HSA were site-directed integrated and stably expressed at the ScltI site. • The ScltI site fulfills the expression of exogenous proteins of different molecular weight sizes (15-190 kDa).

2.
Eur J Pediatr ; 2023 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-36708384

RESUMO

The aim was to develop a model to predict the adult height (AH) of idiopathic central precocious puberty (ICPP) girls who underwent gonadotropin-releasing hormone analog (GnRHa) treatment. Data analysis included 258 girls with ICPP. Among them, 101 girls who reached final AH (FAH) with GnRHa treatment were analyzed to verify three previous prediction models and develop a unique model based on multiple linear regression. The control group consisted of 41 untreated ICPP girls. Moreover, 116 girls treated with GnRHa who almost attained FAH were included for external validation. Based on our cohorts, all of the three previously published models underestimated the FAH with an R of 0.667, 0.793, and 0.664. The AH prediction model was built as follows: Calculated AH (cm) = 1.89630 * Height SDS + 2.29927 * Height SDS for bone age + 0.40776 * Target height + 100.16684 (R2 = 0.66 and adjusted R2 = 0.65). Internal validation showed a mean root mean squared error (RMSE) of 2.16 cm and a mean absolute error (MAE) of 1.64 cm. External validation showed that a significant error (> 1 SD) appeared only in 7 of 116 girls (6.0%). The model is displayed on the website: http://cpppredict.shinyapps.io/dynnomapp . CONCLUSION: A model for predicting the AH of girls with ICPP was developed incorporating the variables of height SDS, height SDS for bone age, and target height. The internal and external validation ensures an appropriate degree of discrimination and calibration of the prediction model. WHAT IS KNOWN: • Uncertainty prevails as how to predict the adult height of patients with central precocious puberty following gonadotropin-releasing hormone analog treatment. • Previous models for predicting adult height of girls with idiopathic central precocious puberty have not been proven translational to the Chinese population. WHAT IS NEW: • This study develops a new model for predicting the adult height of idiopathic central precocious puberty girls who underwent gonadotropin-releasing hormone analog treatment. • The internal and external validation assures a good degree of discrimination and calibration of the prediction model in this study.

3.
BMJ ; 380: e072909, 2023 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-36653033

RESUMO

OBJECTIVE: To assess the prospective associations of circulating levels of omega 3 polyunsaturated fatty acid (n-3 PUFA) biomarkers (including plant derived α linolenic acid and seafood derived eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) with incident chronic kidney disease (CKD). DESIGN: Pooled analysis. DATA SOURCES: A consortium of 19 studies from 12 countries identified up to May 2020. STUDY SELECTION: Prospective studies with measured n-3 PUFA biomarker data and incident CKD based on estimated glomerular filtration rate. DATA EXTRACTION AND SYNTHESIS: Each participating cohort conducted de novo analysis with prespecified and consistent exposures, outcomes, covariates, and models. The results were pooled across cohorts using inverse variance weighted meta-analysis. MAIN OUTCOME MEASURES: Primary outcome of incident CKD was defined as new onset estimated glomerular filtration rate <60 mL/min/1.73 m2. In a sensitivity analysis, incident CKD was defined as new onset estimated glomerular filtration rate <60 mL/min/1.73 m2 and <75% of baseline rate. RESULTS: 25 570 participants were included in the primary outcome analysis and 4944 (19.3%) developed incident CKD during follow-up (weighted median 11.3 years). In multivariable adjusted models, higher levels of total seafood n-3 PUFAs were associated with a lower incident CKD risk (relative risk per interquintile range 0.92, 95% confidence interval 0.86 to 0.98; P=0.009, I2=9.9%). In categorical analyses, participants with total seafood n-3 PUFA level in the highest fifth had 13% lower risk of incident CKD compared with those in the lowest fifth (0.87, 0.80 to 0.96; P=0.005, I2=0.0%). Plant derived α linolenic acid levels were not associated with incident CKD (1.00, 0.94 to 1.06; P=0.94, I2=5.8%). Similar results were obtained in the sensitivity analysis. The association appeared consistent across subgroups by age (≥60 v <60 years), estimated glomerular filtration rate (60-89 v ≥90 mL/min/1.73 m2), hypertension, diabetes, and coronary heart disease at baseline. CONCLUSIONS: Higher seafood derived n-3 PUFA levels were associated with lower risk of incident CKD, although this association was not found for plant derived n-3 PUFAs. These results support a favourable role for seafood derived n-3 PUFAs in preventing CKD.


Assuntos
Ácidos Graxos Ômega-3 , Insuficiência Renal Crônica , Humanos , Pessoa de Meia-Idade , Ácido alfa-Linolênico , Estudos Prospectivos , Ácidos Graxos Insaturados , Insuficiência Renal Crônica/epidemiologia , Fatores de Risco
4.
Curr Microbiol ; 80(2): 58, 2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36588112

RESUMO

Nitrogen is an important factor affecting crop yield, but excessive use of chemical nitrogen fertilizer has caused decline in nitrogen utilization and soil and water pollution. Reducing the utilization of chemical nitrogen fertilizers by biological nitrogen fixation (BNF) is feasible for green production of crops. However, there are few reports on how to have more ammonium produced by nitrogen-fixing bacteria (NFB) flow outside the cell. In the present study, the amtB gene encoding an ammonium transporter (AmtB) in the genome of NFB strain Kosakonia radicincitans GXGL-4A was deleted and the △amtB mutant was characterized. The results showed that deletion of the amtB gene had no influence on the growth of bacterial cells. The extracellular ammonium nitrogen (NH4+) content of the △amtB mutant under nitrogen-free culture conditions was significantly higher than that of the wild-type strain GXGL-4A (WT-GXGL-4A), suggesting disruption of NH4+ transport. Meanwhile, the plant growth-promoting effect in cucumber seedlings was visualized after fertilization using cells of the △amtB mutant. NFB fertilization continuously increased the cucumber rhizosphere soil pH. The nitrate nitrogen (NO3-) content in soil in the △amtB treatment group was significantly higher than that in the WT-GXGL-4A treatment group in the short term but there was no difference in soil NH4+ contents between groups. Soil enzymatic activities varied during a 45-day assessment period, indicating that △amtB fertilization influenced soil nitrogen cycling in the cucumber rhizosphere. The results will provide a solid foundation for developing the NFB GXGL-4A into an efficient biofertilizer agent.


Assuntos
Compostos de Amônio , Cucumis sativus , Bactérias Fixadoras de Nitrogênio , Plântula , Nitrogênio/metabolismo , Bactérias/metabolismo , Solo/química , Proteínas de Membrana Transportadoras , Fertilizantes/análise
5.
Int J Biol Macromol ; : 123402, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36702221

RESUMO

In this work, waxy maize starch nanocrystals were prepared by mixed acid of sulfuric acid and hydrochloric acid for the first time. Physicochemical properties, crystalline structure, and particle size of starch nanocrystals prepared by mixed acid (HSNC) were measured. The results showed that there was no difference in particle morphology, group structure, and surface elements of HSNC and starch nanocrystals prepared by sulfuric acid (SNC), which was a conventional preparation method. The yield of HSNC was lower than that of SNC. However, the preparation time of HSNC was greatly shortened to 1 h which is only 0.83 % of the time (5 d) to prepare SNC by the sulfuric acid, and HSNC showed higher relative crystallinity and smaller size than those of SNC. In addition, when the ratio of sulfuric acid and hydrochloric acid to provide H ion concentration was 1:1 to hydrolyze starch for >1 h, the crystal pattern of HSNC would be changed to V-typed, while the crystal pattern of SNC was still A-typed. Thus, this work provided efficient method for preparing starch nanocrystals is provided, which can replace sulfuric acid hydrolysis to prepare SNC.

6.
Rheumatol Ther ; 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36662442

RESUMO

INTRODUCTION: We sought to identify and compare treatment response groups based on individual patient responses (rather than group mean response) over time on the Clinical Disease Activity Index (CDAI) for rheumatoid arthritis (RA), in patients treated with baricitinib 4-mg in 4 phase 3 studies. METHODS: Trajectory subgroups were identified within each study using growth mixture modeling. Following grouping, baseline characteristics and disease measures were summarized and compared. RESULTS: In each study, three response trajectories were identified. In the three studies of patients naïve to biological disease-modifying anti-rheumatic drugs (bDMARDs) patients had, on average, high disease activity, as measured by CDAI. In these studies, a group of rapid responders (65-71% of patients) had the lowest baseline CDAI scores and achieved mean CDAI ≤ 10 by week 16. Gradual responders (10-17%) had higher baseline CDAI, but generally achieved low disease activity (CDAI ≤ 10) by week 24. A group of partial responders (18-22%) had higher baseline CDAI and did not achieve mean CDAI ≤ 10. In bDMARD-experienced patients, the subgroups were rapid responders, who achieved mean CDAI ≤ 10 (42% of patients); partial responders, with mean CDAI decrease of ~ 15 points from baseline (42% of patients); and limited responders (15% of patients). Changes in modified total sharp score (mTSS; assessed only in biologic-naïve patients) were below the smallest detectable difference at 24/52 weeks for > 90% of patients in each group, excepting partial responders in RA-BEGIN (≥ 75% no detectable change). CONCLUSION: In patients receiving baricitinib 4-mg, lower baseline CDAI was generally associated with rapid response, while higher baseline CDAI scores were generally seen for patients who either reached treatment targets more gradually, or who had a partial or limited response. Maintenance of response was observed with continued baricitinib treatment in all response groups and generally included maintenance of mTSS.


Baricitinib is an oral agent widely approved for the treatment of moderately to severely active rheumatoid arthritis). Although baricitinib (and other agents) have demonstrated efficacy at the population level, treatment responses vary considerably between individual patients. This study assessed four baricitinib phase 3 clinical studies and categorized patient responses into response groups based on the Clinical Disease Activity Index (CDAI) using a growth mixture model. We then evaluated baseline characteristics and corresponding disease measures within the response groups. In patients with no prior treatment with biological disease-modifying anti-rheumatic drugs (bDMARDs), 65­71% of patients had rapid responses to treatment, while smaller groups had gradual (10­17%) or partial (18­22%) responses. In patients with prior bDMARD experience, rapid and partial responders each comprised 42% of patients while 15% had limited response. Gradual responders generally had higher baseline CDAI versus rapid responders, but achieved low disease activity (LDA) by 24, versus 12 weeks for rapid responders. Across response groups, patients who continued treatment generally maintained their response up to 52 weeks, and where joint erosion was assessed (in bDMARD-naïve patients), generally saw maintenance of joints during continued therapy. The identification of a gradual responder group, which demonstrated good response but required more time to achieve LDA, is relatively novel and should be considered when setting treatment expectations, particularly in patients with high baseline disease activity. In addition, in bDMARD-experienced patients, many patients did not achieve LDA but maintained a substantial partial response with continued therapy.

7.
Eur J Med Chem ; 249: 115131, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36669399

RESUMO

Antimicrobial peptides (AMPs) show great promise for clinical applications, but the utility of naturally occurring AMPs is often limited by their stability. Here, we used a rational design approach to improve the characteristics of a pair of inactive peptides, tilapia piscidin 1 and 2 (TP1 and TP2). From each starting peptide, we generated a series of novel derivatives by substituting residues to adjust cationic charge density, percent hydrophobicity and hydrophilicity/hydrophobicity coefficients. This approach yielded a novel peptide, TP2-5 (KKCIAKAILKKAKKLLKKLVNP), that exhibits significant bactericidal potency, low cytotoxicity and high stability. The designed peptide further showed antibiofilm activity, rapid antibacterial action and a low capacity to induce bacterial resistance. Importantly, we also demonstrated that TP2-5 can protect mice in a Vibrio vulnificus-infected wound model. Therefore, our peptide modification strategy successfully generated a novel AMP with high potential for future clinical application.

8.
J Immunother Cancer ; 11(1)2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36657812

RESUMO

BACKGROUND: Immune-checkpoint inhibitors (ICIs) remain ineffective in a large group of non-small cell lung cancer (NSCLC) patients. Mucosal-associated invariant T (MAIT) cells, a population of unconventional innate-like T lymphocytes abundant in the human body, play important roles in human malignancies. Little is known about the immune characteristics of MAIT cells in NSCLC and correlation with prognosis and response rate of ICIs treatment. METHODS: To investigate the distribution, activation status, and function of MAIT cells in NSCLC patients and their correlations with anti-PD-1 immunotherapy, MAIT cells in peripheral blood, tumor and paratumor samples from NSCLC patients with or without anti-PD-1 immunotherapy were analyzed using flow cytometry and single-cell RNA-sequencing. RESULTS: MAIT cells were enriched in the tumor lesions of NSCLC patients migrating from peripheral blood via the CCR6-CCL20 axis. Both peripheral and tumor-infiltrating MAIT cells displayed an exhausted phenotype with upregulated PD-1, TIM-3, and IL-17A while less IFN-γ. Anti-PD-1 therapy reversed the function of circulating MAIT cells with higher expression of IFN-γ and granzyme B. Subcluster MAIT-17s (defined as cells highly expressing exhausted and Th17-related genes) mainly infiltrated in the non-responsive tissues, while the subcluster MAIT-IFNGRs (cells expressing genes related to cytotoxic function) were mainly enriched in responsive tissues. Moreover, we found predictive value of circulating MAIT cells for anti-PD-1 immunotherapy in NSCLC patients. CONCLUSIONS: MAIT cells shifted to an exhausted tumor-promoting phenotype in NSCLC patients and the circulating MAIT subset could be a predictor for patients who respond to anti-PD-1 immunotherapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Células T Invariantes Associadas à Mucosa , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Prognóstico , Imunoterapia
9.
Antioxidants (Basel) ; 12(1)2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36671063

RESUMO

Dihydromyricetin (DHY), the main flavonoid component in Ampelopsis grossedentata, has important benefits for health. The present study aimed to investigate the exact effects and possible mechanisms of DHY on diabetic cardiomyopathy (DCM). Male C57BL/6 mice and sirtuin 3 (SIRT3) knockout (SIRT3-KO) mice were injected with streptozotocin (STZ) to induce a diabetic model. Two weeks later, DHY (250 mg/kg) or carboxymethylcellulose (CMC) were administrated once daily by gavage for twelve weeks. We found that DHY alleviated fasting blood glucose (FBG) and triglyceride (TG) as well as glycosylated hemoglobin (HbA1c) levels; increased fasting insulin (FINS); improved cardiac dysfunction; ameliorated myocardial hypertrophy, fibrosis and injury; suppressed oxidative stress, inflammasome and necroptosis; but improved SIRT3 expression in STZ-induced mice. Neonatal rat cardiomyocytes were pre-treated with DHY (80 µM) with or without high glucose (HG) stimulation. The results showed that DHY attenuated cell damage but improved SIRT3 expression and inhibited oxidative stress, inflammasome and necroptosis in cardiomyocytes with high glucose stimulation. Moreover, the above protective effects of DHY on DCM were unavailable in SIRT3-KO mice, implying a promising medical potential of DHY for DCM treatment. In sum, DHY improved cardiac dysfunction; ameliorated myocardial hypertrophy, fibrosis and injury; and suppressed oxidative stress, inflammation and necroptosis via SIRT3 activation in STZ-induced diabetic mice, suggesting DHY may serve as a candidate for an agent to attenuate diabetic cardiomyopathy.

10.
Acta Cardiol Sin ; 39(1): 151-161, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36685157

RESUMO

Background: The epidemiological characteristics of sudden death may vary according to ethnicity and country. This study aimed to analyze the distribution of sudden deaths in Taiwan, as well as their epidemiological characteristics and the associated meteorological factors. Methods: The Chin-Shan Community Cardiovascular Cohort is a longitudinal study conducted in a community in Taipei County since July 1990. A total of 3,602 individuals aged 35 years and older were included in the study. Sudden deaths were prospectively recorded and analyzed. Results: Eighty-two (68.3% men) sudden deaths (8.56% of all deaths) were reported from July 1990 to December 2008, of which 87.8% were caused by cardiovascular disease. However, only 36.6% were attributed to coronary artery disease. There was a higher incidence of sudden death in the winter [incidence rate ratio (IRR): 1.91, 95% confidence interval (CI): 1.42-2.56], compared to fall, and the highest peak of sudden death occurred between 16:00-20:00 (IRR: 3.00, 95% CI: 1.72-5.22) compared to 00:00-04:00 as the reference group. Additionally, a relatively higher mean temperature was associated with a lower risk of sudden death (IRR: 0.96, 95% CI: 0.93-0.98). On the other hand, higher humidity (IRR: 1.09, 95% CI: 1.02-1.16) and discomfort index (IRR: 1.03, 95% CI: 1.003-1.05) were associated with increased risks of sudden death. Conclusions: Meteorological factors and circadian patterns were associated with sudden death among our Taiwanese cohort. Our study findings may support potential protective behavior for sudden death via weather forecasting.

11.
Bioconjug Chem ; 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36626242

RESUMO

In addition to residual cancer cells, the surgery resection-induced hyperinflammatory microenvironment is a key factor that leads to postsurgical cancer recurrence. Herein, we developed a dual-functional nanodrug Asp@cLANVs for postsurgical recurrence inhibition by loading the classical anti-inflammatory drug aspirin (Asp) into cross-linked lipoic acid nanovesicles (cLANVs). The Asp@cLANVs can not only kill residual cancer cells at the doses comparable to common cytotoxic drugs by synergistic interaction between Asp and cLANVs, but also improve the postsurgical inflammatory microenvironment by their strongly synergistic anti-inflammation activity between Asp and cLANVs. Using mice bearing partially removed NCI-H460 tumors, we found that Asp@cLANVs gave a much lower recurrence rate (33.3%) compared with the first-line cytotoxic drug cisplatin (100%), and no mice died for at least 60 days after Asp@cLANV treatment while no mouse survived beyond day 43 in the cisplatin group. This dual-functional nanodrug constructs the first example that combines residual cancer cell killing and postoperative inflammation microenvironment improvement to suppress postsurgical cancer recurrence.

12.
Heliyon ; 9(1): e12770, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36691539

RESUMO

Introduction: Heart Failure (HF) is a key area of research in human medicine, and traditional Chinese medicine (TCM) is an important branch of this field. This study aimed to use bibliometric methods to sort out the trajectory of TCM research on HF in this century (2000-2022) from a high dimension and to analyze its characteristics, hotspots and frontiers. Methods: In this study, the search formula "TS=(("traditional Chinese medicine") OR ("Chinese medicine")) AND TS=("heart failure")" was used to find relevant studies included in the Web of Science Core Collection from 2000 to 2022. Targeted literature records were analyzed and mapped using CiteSpace and VOSviewer. Results: The authors and collaborators of this study were still in the formation process, but several well-known scholars were included: YONG WANG, WEI WANG, etc. The main research institutions in this research area were Beijing Univ Chinese Med, China Acad Chinese Med Sc, etc. The main country of study was China. Current research hotspots and frontiers were Qili Qiangxin capsules, extracts (Tanshinone ⅡA, Panax ginseng, etc.), cardiac hypertrophy, ventricular remodeling, oxidative stress, signaling pathways, network pharmacology, etc. Influential journals that publish papers in this field were the Journal of Ethnopharmacology, Scientific Reports, Biomedicine & Pharmacotherapy, etc. The top 3 co-cited journals were Circulation, J ethnopharmacol, and J am coll cardiol. Conclusions: We analyzed valuable details in TCM research on HF in the 21st century, which may help researchers identify potential collaborators and partner institutions, hotspots, and frontiers in the field.

13.
Aesthetic Plast Surg ; 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36694050

RESUMO

OBJECTIVE: The present study compiled evidence on the efficacy of botulinum toxin A (BTX) for management of bruxism. METHODS: A literature review that included randomized control, cohort, as well as observational studies published between January 2000 and November 2022 was conducted. All studies related to BTX injections administered into the masseters of patients with bruxism were included. Primary outcomes were measured by performing a meta-analysis of changes in maximal biting forces and pain severity and meta-regression of the effects of the BTX dose. RESULTS: Ten studies were included for quantitative analysis. The analysis of the maximal biting force after BTX injections demonstrated a significant reduction at 1 month or less compared with both oral splints (P < 0.000001) and saline injections (P = 0.01). BTX continued to outperform oral splinting (P = 0.001) and saline placebos (P = 0.03) at 3 months. Between 3 and 6 months, a significantly higher maximal biting strength was observed in the BTX group than the oral splinting group (P < 0.00001). No significant differences in the maximal biting force were observed between the BTX and saline placebo groups (P = 0.50). A similar trend was observed in the analysis of pain reduction after botulinum treatment. Additionally, for every unit increase in the BTX dose, pain severity decreased by 0.0831 points (P = 0.0011). CONCLUSION: BTX is effective in reducing biting strength and pain severity. BTX effects are evident at less than 4 weeks, peak between 5 and 8 weeks, and last for up to 24 weeks. Higher BTX doses result in greater improvement in pain. Although BTX benefits manifest earlier, they gradually diminish, and oral splinting exerts a more enduring effect, especially after 9-12 weeks. BTX injections into masseters are recommended as management options for bruxers, especially for those having difficulties complying with wearing oral splints or those seeking earlier symptom relief. However, future studies should determine BTX effects beyond 24 weeks and after repetitive injections and how bruxers of different ages or genders respond to treatment. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

14.
Eur J Neurosci ; 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36601787

RESUMO

In task switching, an interaction between task and response is often observed, with response repetition (RR) benefits in task-repeat trials and RR costs in task-switch trials. The theoretical accounts of the RR effect remain controversial, and neuroscience evidence is scarce. The present study utilized the event-related potentials (ERPs) method to explore the neural mechanism underlying the RR effect by adopting a cued task-switching paradigm. The ERP results revealed the interaction between task and response in the P3b time window, with a response switch positivity under task-repetition conditions and an RR positivity under task-switching conditions. In addition, there were RR positivity in the N2 irrespective of task transition and in the late component (LC, 550-600 ms) that only under the task repetition condition. On the individual level, the RR benefit positively correlated with the RR positivity in the LC, while the RR costs negatively correlated with RR positivity in the N2/P3 component. These results suggest that both response reconfiguration and episodic-retrieval make contributions to the RR effects, which were also discussed in terms of predictive model for a domain-general inference and learning of perceptual categories.

15.
Artigo em Inglês | MEDLINE | ID: mdl-36673816

RESUMO

(1) Background: The main research aim of this paper is to investigate the commonly stocked medicines in Chinese households. Firstly, a large number of questionnaires were collected to uncover the problem: most Chinese families have the habit of stocking their family medicine boxes. However, there is a lack of a standardized, systematic, and scientific list of household medicine stockpiles. As a result, there are major problems in stocking medicines in households: (1) There is little connection between the type and quantity of medicines stocked and real life; (2) The expiration date of medicines leads to misuse and waste of medicines; (3) The existing list of medicines can provide little help. (2) Methods: The preliminary drug stock list was summarized through case studies; the authenticity of the questions and the credibility of the list were verified through interviews; the number of different types of drugs and the relationship between the resident's perception of the importance of drugs and their frequency of use was determined through questionnaires; the authenticity of the list was verified through interviews with senior doctors. (3) Results: We finally composed a scientific and practical list of common household medicines, developed a practical domestic-medication system for Chinese families, and conducted validation studies, which received the approval of senior doctors. (4) Conclusions: (1) Chinese families need to prepare medicines according to the actual composition of the family; (2) Chinese families need a scientific and systematic list of commonly prepared medicines; and (3) in addition to the types of medicines, it is also necessary to consider the number of individual types of medicines to be stocked.


Assuntos
Medicamentos de Ervas Chinesas , Saúde Pública , Humanos , Inquéritos e Questionários , Características da Família , Medicamentos de Ervas Chinesas/uso terapêutico
16.
Artigo em Inglês | MEDLINE | ID: mdl-36673924

RESUMO

It is important to investigate how to achieve carbon unlocking in the transport sector, especially in transport infrastructure, in order to contribute to the achievement of carbon neutrality targets and the 2030 Sustainable Development Goals. This study aims to investigate the necessary and sufficient conditions to achieve carbon unlocking in transport infrastructure. To achieve this, a combination of partial least squares structural equation modeling (PLS-SEM) and necessary condition analysis (NCA) methods have been used to examine whether there are unidentified necessity factors beyond the currently recognized 'technology-in-institution' (TIC) lock-in. This study also explores how the carbon unlocking of transport infrastructure can be achieved through the unlocking of relevant factors. The study includes 366 points from a subjective questionnaire from the government, transport infrastructure researchers, and relevant businesspeople. We found that, at the adequacy level, achieving institutional and technological unlocking is sufficient and economic factors have little impact on transport infrastructure (0.06), and that institutional and technical factors have a large impact on carbon unlocking (0.453, 0.280); however, from the necessary point of view, carbon unlocking at the economic level is necessary to achieve the goal of a medium to high level of carbon unlocking. To achieve carbon unlocking at this level (over 50%), a combination of technological, institutional, and economic factors is required. To achieve full carbon unlocking, the technology, system, and economy need to be at least 0.533, 0.791, and 0.63 unlocked. Therefore, we can conclude that by using the joint analysis of PLS-SEM and NCA, we have achieved an extension of the traditional TIC and identified sufficient and necessary conditions to achieve a medium to high degree of carbon unlocking.


Assuntos
Carbono , Desenvolvimento Sustentável , Análise dos Mínimos Quadrados , Análise de Classes Latentes , Tecnologia
17.
Cell Mol Life Sci ; 80(2): 41, 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36633714

RESUMO

SRC is the first identified oncogene, and its aberrant activation has been implicated as a driving event in tumor initiation and progression. However, its role in cancer stemness regulation and the underlying regulatory mechanism are still elusive. Here, we identified a YAP1 tyrosine phosphorylation-dependent YAP1-KLF5 oncogenic module, as the key downstream mediator of SRC kinase regulating cancer stemness and metastasis in triple-negative breast cancer (TNBC). SRC was overexpressed in TNBC patient tissues and its expression level was highly correlated with the tumor malignancy. SRC activation induced, while inhibition of SRC kinase reduced the cancer stemness, tumor cell growth and metastasis in vitro and in vivo. Transcriptomic and proteomic analysis revealed that SRC-mediated YAP1 tyrosine phosphorylation induced its interaction with Kruppel-like factor 5 (KLF5) to form a YAP1/TEAD-KLF5 complex in TNBC cells. YAP1-KLF5 association further promoted TEAD-mediated transcriptional program independently of canonical Hippo kinases, which eventually gave rise to the enhanced cancer stemness and metastasis. Disruption of YAP1-KLF5 module in TNBC cells dramatically attenuated the SRC-induced cancer stemness and metastasis in vitro and in vivo. Accordingly, co-upregulations of SRC and YAP1-KLF5 module in TNBC tissues were significantly positively correlated with the tumor malignance. Altogether, our work presents a novel tyrosine phosphorylation-dependent YAP1-KLF5 oncogenic module governing SRC-induced cancer stemness and metastasis in TNBC. Therefore, targeting YAP1/KLF5-mediated transcription may provide a promising strategy for TNBC treatment with SRC aberrantly activation.


Assuntos
Proteínas Tirosina Quinases , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/metabolismo , Proteômica , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Quinases da Família src/metabolismo , Proliferação de Células , Tirosina , Linhagem Celular Tumoral , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo
18.
Sci Rep ; 13(1): 349, 2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36611127

RESUMO

We aim to investigate the alteration in disease activity of ankylosing spondylitis (AS) individuals before, during, and after the COVID-19 wave in Taiwan by using electronic medical-record management system (EMRMS). We identified 126 AS individuals from the single center, and gathered data of the three disease activities (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI], Ankylosing Spondylitis Disease Activity Score with erythrocyte sedimentation rate [ASDAS-ESR], and Ankylosing Spondylitis Disease Activity Score with C-Reactive Protein [ASDAS-CRP]) by using EMRMS before (7 February to 1 May, 2021), during (2 May to 24 July, 2021), and after the COVID-19 wave (25 July to 16 October, 2021). We compared the disease activity measures of the three phases through a paired t test. Among the 126 individuals, CRP was significantly higher during the COVID-19 wave (0.2 (0.1, 0.5) mg/dl, p = 0.001) than before the wave (0.2 (0.1, 0.4) mg/dl), ESR (8.0 (4.0, 15.0) mm/h, p = 0.003) and ASDAS-ESR (1.4 (1.0, 1.9), p = 0.032) were significantly higher after the wave than during the wave (6.0 (3.0, 12.0) mm/h and 1.2 (0.9, 1.8) mm/h) e. ESR, CRP, ASDAS-ESR and ASDAS-CRP were all significant higher after COVID-19 wave than before. The disease activities of AS individuals in Taiwan worsened after 2021 COVID-19 wave in Taiwan.


Assuntos
COVID-19 , Espondilite Anquilosante , Humanos , Espondilite Anquilosante/epidemiologia , Taiwan/epidemiologia , Registros Eletrônicos de Saúde , Índice de Gravidade de Doença , COVID-19/epidemiologia , Proteína C-Reativa/análise , Sedimentação Sanguínea
19.
Int J Biol Macromol ; 229: 443-451, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36599382

RESUMO

A novel mussel-inspired adhesive hydrogel with enhanced adhesion based on methacrylated catechol-chitosan (MCCS) and dopamine methacrylate (DMA) was prepared via photopolymerization. The structure and morphology of the MCCS/DMA adhesive hydrogel were investigated by using FTIR, NMR, XRD, TG, and SEM. The rheological and texture properties, swelling and degradation characteristics, as well as the adhesion mechanism of the hydrogels were also examined. These results revealed that the MCCS/DMA hydrogels have a dense double cross-linking network structure with porous internal microstructures, and exhibited controllable swelling and degradation properties, good thermostability, and stable rheological characteristics. Furthermore, the adhesive mechanism of MCCS/DMA hydrogel has been confirmed by the FTIR and 2D correlation FTIR spectroscopy. Additionally, the results of in vitro cytotoxicity assessment indicated that the resulting hydrogels have good cytocompatibility. Overall, the MCCS/DMA adhesive hydrogel may have potential applications in medical bioadhesives.

20.
Food Chem ; 409: 135238, 2023 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-36584531

RESUMO

This study focused on the effects of freeze drying (FD) and sprays drying (SD) on the structure and emulsifying properties of yam soluble protein (YSP). The results showed that the surface hydrophobicity (Ho) value, free sulfhydryl group (SH) content, turns content, denaturation temperature and enthalpy value of spray-dried YSP (SD-YSP) were higher than freeze-dried YSP (FD-YSP), but the apparent hydrodynamic diameter (Dh) value of SD-YSP was smaller. The smaller Dh, higher Ho and free SH led to higher percentage of adsorbed proteins and stronger binding between protein and oil droplet in emulsions. Thus, the emulsifying properties of SD-YSP were better, and the SD-YSP-stabilized emulsion had better dynamical rheological properties. Molecular dynamics (MD) simulations suggested that some intramolecular disulfide bonds and hydrogen bonds of dioscorin were broken, and some helices transformed into turns during the SD process. These structural changes resulted in better thermal stability and emulsification properties of SD-YSP.


Assuntos
Dioscorea , Simulação de Dinâmica Molecular , Secagem por Atomização , Liofilização/métodos , Emulsões/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...