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Background: Thyroid hormones significantly influence cardiovascular pathophysiology, yet their prognostic role in acute aortic dissection (AAD) remains inadequately explored. This study assesses the prognostic value of thyroid hormone levels in AAD, focusing on the mediating roles of renal function and coagulation. Methods: We included 964 AAD patients in this retrospective cohort study. Utilizing logistic regression, restricted cubic splines, and causal mediation analysis, we investigated the association between thyroid hormones and in-hospital mortality and major adverse cardiovascular events (MACEs). Results: In AAD patients overall, an increase of one standard deviation in FT4 levels was associated with a 31.9% increased risk of MACEs (OR 1.319; 95% CI 1.098-1.584) and a 36.1% increase in in-hospital mortality (OR 1.361; 95% CI 1.095-1.690). Conversely, a higher FT3/FT4 ratio was correlated with a 20.2% reduction in risk of MACEs (OR 0.798; 95% CI 0.637-0.999). This correlation was statistically significant predominantly in Type A AAD, while it did not hold statistical significance in Type B AAD. Key renal and coagulation biomarkers, including blood urea nitrogen, creatinine, cystatin C, prothrombin time ratio, prothrombin time, and prothrombin time international normalized ratio, were identified as significant mediators in the interplay between thyroid hormones and MACEs. The FT3/FT4 ratio exerted its prognostic influence primarily through the mediation of renal functions and coagulation, while FT4 levels predominantly impacted outcomes via a partial mediation effect on coagulation. Conclusion: FT4 levels and the FT3/FT4 ratio are crucial prognostic biomarkers in AAD patients. Renal function and coagulation mediate the association between the thyroid hormones and MACEs.
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Dissecção Aórtica , Coagulação Sanguínea , Hormônios Tireóideos , Humanos , Masculino , Feminino , Prognóstico , Estudos Retrospectivos , Pessoa de Meia-Idade , Hormônios Tireóideos/sangue , Coagulação Sanguínea/fisiologia , Dissecção Aórtica/sangue , Dissecção Aórtica/fisiopatologia , Rim/fisiopatologia , Idoso , Biomarcadores/sangue , Mortalidade Hospitalar , Adulto , Doença AgudaRESUMO
Background: Managing systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) is pivotal in acute aortic dissection (AAD) care. However, no prior studies have jointly analyzed the trajectories of these parameters. This research aimed to characterize their joint longitudinal trajectories and investigate the influence on AAD prognosis. Methods: We included AAD patients from the Medical Information Mart for Intensive Care (MIMIC)-IV database. Using group-based multi-trajectory modeling (GBMTM), we identified combined trajectories of SBP, DBP, and HR within the initial 24 h of intensive care unit (ICU) admission. Cox proportional hazard regression, log-binomial regression, and logistic regression were employed to assess the association between trajectory groups and mortality outcomes. Results: Data from 337 patients were analyzed. GBMTM identified five combined trajectory groups. Group 1 featured rapidly declining SBP and DBP with high pulse pressure and low HR; Group 2 showed high to moderate SBP with slight rebound and persistently low HR; Group 3 displayed persistently moderate BP and HR; Group 4 was characterized by moderate blood pressure with persistently high HR; and Group 5 had high to moderate SBP with slight rebound, high but gradually declining DBP, and slightly high HR. Group 3 demonstrated a lower risk of mortality, with an adjusted hazard ratio of 0.32 (95 % CI, 0.14-0.74), and the adjusted relative risks for in-hospital, 30-day, and 1-year mortalities were 0.37 (95 % CI, 0.15-0.87), 0.25 (95 % CI, 0.10-0.62), and 0.41 (95 % CI, 0.22-0.79), respectively. The time-independent C-index curve demonstrated that the multi-trajectory groups had higher C-index values than any univariate trajectory groups or admission values of SBP, DBP, and HR. Conclusions: Utilization of GBMTM can yield data-driven insights to identify distinct subphenotypes in AAD patients. The combined trajectories of SBP, DBP, and HR within 24 h of ICU admission significantly influenced the mortality rate.
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BACKGROUND: Pushing is a typical workplace activity that may result in musculoskeletal disorders (MSDs). A convenient method of assessing the risk of MSDs is to determine the association between the force applied and the subjective rating of force exertion. OBJECTIVES: This study aimed to determine the relationship between the subjective rating of force exertion and the force applied to both a fixed and a movable handle. It also aimed to confirm that the participants could apply a higher one-handed push force at shoulder height than at elbow height. METHODS: A one-handed pushing experiment was conducted. In the push-to-scale session, the participants pushed a handle fixed on a rig on four levels on the CR-10 scale. The push force was measured. In the force-rating session, the participants rated their force exertions when pushing a movable handle with metal blocks suspended on the two sides. The subjective ratings on the CR-10 were recorded. RESULTS: The one-handed push force at shoulder height was significantly higher than that at elbow height. More effort was needed to push on a movable handle than a fixed one. Two regression models were established to describe the relationship between the push force and the subjective ratings of pushing for each of the fixed and movable handles, respectively. The correlation coefficient results showed that these models are adequate to describe the relationship between the one-handed push force and the ratings of the CR-10 scale. CONCLUSION: Participants applied a higher one-handed push force at shoulder height than at elbow height was confirmed. Participants needed more efforts to push the movable handle under the same CR-10 level than the fixed handle. The predictive models developed in this study may be used to estimate the push force for one-handed pushing tasks when assessing the risk of MSDs.
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To investigate household vulnerability for inability to cope with medical expenditure shock, we propose a method of measuring household vulnerability to medical expenditure shock by allowing for the heteroscedasticity and dependence of medical expenditure shock and income shock. Using the data from China Health and Nutrition Survey, we estimate the vulnerability of Chinese households, and further investigate crucial characteristics associated with it by comparing the vulnerability levels among groups with different characteristics and an empirical regression with Shorrocks-Shapely decomposition of R squared. Our research shows that health status contributes most to the household vulnerability, and good health helps to reduce the household's vulnerability. Households with stable income and high-education have greater ability to cope with uncertain medical expenditure, and are less vulnerable. Medical insurance plays a limited role in reducing household vulnerability, and the specific type of medical insurance has little influence. All of these findings are conducive to identifying vulnerable households and designing policies to reduce the vulnerability of households.
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OBJECTIVE: Addressing the increasing global health issue of childhood obesity, exacerbated by pervasive food marketing, this study critically evaluated China's food marketing policies in comparison with international best practices, aiming to uncover policy content and implementation gaps and inform policy enhancement strategies. METHOD: Three key indicators were utilized from the Healthy Food-Environment Policy Index (Food-EPI)'s food promotion domain. A panel of experts (n = 13) from academic institutions, China Centers for Disease Control and Prevention, and the food industry assessed the Chinese government's policy scores and implementation levels concerning food marketing. Benchmarked against international best practices using the Food-EPI process, this evaluation encompassed context analysis, data collection, evidence-based policy action, government validation, policy rating, scoring, and results translation for government and stakeholders. The three chosen indicators specifically addressed childhood overweight- and obesity-related food marketing in broadcast media (Indicator 1), non-broadcast media (Indicator 2), and child gathering settings (Indicator 3). RESULTS: Specifically, Indicator 1, the Single Food Marketing Indicator Score was measured at 2.31 ± 0.38, with an accompanying Food Marketing Policy Implementation Percentage of 46.2%, and Low Implementation Level. For non-broadcast mediums (Indicator 2), these metrics were gauged at 1.77 ± 0.27, 35.4%, and Low Implementation Level, respectively. In child gathering settings (Indicator 3), for efforts curbing unhealthy food promotion, a score of 2.77 ± 0.27, an implementation percentage of 55.4%, and Medium Implementation Level was obtained. Cumulatively, the overarching efficacy of food marketing policy enforcement was determined to be suboptimal, with the consolidated figures being Total Food Marketing Score as 2.28 ± 0.97, Total Food Marketing Policy Implementation Percentage as 45.6%, and Total Food Marketing Policy Implementation Level as Low. CONCLUSION: Like many countries, China's food marketing policies and implementation have room for improvement when compared to international best practices. Recommendations include emphasizing nutritional legislation, fostering stakeholder collaboration, bolstering public health campaigns, and leveraging technology for stringent enforcement.
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Obesidade Infantil , Humanos , Criança , Obesidade Infantil/prevenção & controle , Política Nutricional , Promoção da Saúde/métodos , Indústria Alimentícia , MarketingRESUMO
Photosensitizers have been widely used to cause intratumoral generation of reactive oxygen species (ROS) for cancer therapy, but they are easily disturbed by the autophagy pathway, a self-protective mechanism by mitigating oxidative damage. Hereby, we reported a simple and effective strategy to construct a carrier-free nanodrug, Ce6@CQ namely, based on the self-assembly of the photosensitizer chlorin e6 (Ce6) and the autophagy inhibitor chloroquine (CQ). Specifically, Ce6@CQ avoided the unexpected toxicity caused by the regular nanocarrier and also ameliorated its stability in different conditions. Light-activated Ce6 generated cytotoxic ROS and elicited part of the immunogenic cell death (ICD). Moreover, CQ induced autophagy dysfunction, which hindered self-healing in tumor cells and enhanced photodynamic therapy (PDT) to exert a more potent killing effect and more efficient ICD. Also, Ce6@CQ could effectively accumulate in the xenograft breast tumor site in a mouse model through the enhanced permeability and retention (EPR) effect, and the growth of breast tumors was effectively inhibited by Ce6@CQ with light. Such a carrier-free nanodrug provided a new strategy to improve the efficacy of PDT via the suppression of autophagy to digest ROS-induced toxic substances.
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Neoplasias da Mama , Nanopartículas , Fotoquimioterapia , Porfirinas , Animais , Camundongos , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular Tumoral , Morte Celular Imunogênica , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Autofagia , Porfirinas/farmacologia , Porfirinas/uso terapêuticoRESUMO
Irinotecan (Ir) is commonly employed as a first-line chemotherapeutic treatment for colorectal cancer (CRC). However, tremendous impediments remain to be addressed to surmount drug resistance and ameliorate adverse events. Poly-ADP-Ribose Polymerase (PARP) participates in the maintenance of genome stability and the repair of DNA damage, thus playing a critical role in chemotherapy resistance. In this work, we introduce a novel curative strategy that utilizes nanoparticles (NPs) prepared by dynamic supramolecular co-assembly of Ir and a PARP inhibitor (PARPi) niraparib (Nir) through π-π stacking and hydrogen bond interactions. The Ir and Nir self-assembled Nano-Twin-Drug of (Nir-Ir NPs) could enhance the therapeutic effect on CRC by synergistically inhibiting the DNA damage repair pathway and activating the tumor cell apoptosis process without obvious toxicity. In addition, the Nir-Ir NPs could effectively reverse irinotecan-resistance by inhibiting the expression of multiple resistance protein-1 (MRP-1). Overall, our study underscores the distinctive advantages and potential of Nir-Ir NPs as a complementary strategy to chemotherapy by simultaneously overcoming the Ir resistance and improving the anti-tumor efficacy against CRC.
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Antineoplásicos , Neoplasias Colorretais , Humanos , Irinotecano/farmacologia , Irinotecano/uso terapêutico , Antineoplásicos/química , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Apoptose , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Linhagem Celular TumoralRESUMO
Prostate cancer (PCa) is the second most frequently diagnosed cancer among men, causing a huge number of deaths each year. Traditional chemotherapy for PCa mostly focused on targeting androgen receptors. However, some of the patients would develop resistance to hormonal therapy. In these cases, it is suggested for these patients to administer treatments in combination with other chemotherapeutics. Current chemotherapeutics for metastatic castration-resistant PCa could hardly reach satisfying effects, therefore it is crucial to explore novel agents with low cytotoxicity. Herein, a common drug against the human immunodeficiency virus (HIV), the dolutegravir (DTG) was modified to become a series of dolutegravir-1,2,3-triazole derivatives. Among these compounds, the 4d and 4q derivatives were verified with high anti-tumor efficiency, suppressing the proliferation of the prostate cancer cells PC3 and DU145. These compounds function by binding to the poly (adenosine diphosphate-ribose) polymerase (PARP), inactivating the PARP and inducing DNA damage in cancer cells. It is noteworthy that the 4d and 4q derivatives showed almost no impact on normal cells and mice. Thereby, the results reveal that these dolutegravir-1,2,3-triazole compounds are potential chemotherapeutics for PCa treatment.
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Inibidores de Poli(ADP-Ribose) Polimerases , Neoplasias da Próstata , Masculino , Humanos , Animais , Camundongos , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Dano ao DNA , Piridonas/farmacologia , Piridonas/uso terapêutico , Poli(ADP-Ribose) Polimerases/metabolismo , Linhagem Celular TumoralRESUMO
OBJECTIVE: This study aimed to explore the relationship between diffusion tensor imaging (DTI) parameters, cervical spine alignments, and spinal cord morphological parameters in patients with Hirayama disease (HD). METHODS: In this retrospective cohort study, 41 HD patients were recruited from the Huashan hospital from July 2017 to November 2021. Patients received X-rays, conventional magnetic resonance (MR), and DTI scans in flexion and neutral positions. The DTI parameters assessed were calculated using the region of interest (ROI) method. Paired t-tests were performed on the DTI parameters of neck flexion and neutral position. Cervical spine alignments, including flexion and neutral Cobb angles, were measured, and range of motion (ROM) was calculated. Spinal cord morphological parameters were measured, including spinal cord atrophy (SCA) and loss of attachment (LOA). Spearman's correlation analysis between DTI parameters, cervical spine alignments, and spinal cord morphological parameters was performed. RESULTS: In comparing DTI parameters, segments of the C3/4, C4/5, C6/7, and lower cervical spine were significantly different, while segments of C5/6 were not significantly different. In Spearman's correlation analysis, the flexion Cobb angle was significantly correlated with the fractional anisotropy (FA) value (R2 = .111, P = .033) and apparent diffusion coefficient (ADC) value (R2 = .119, P = .027). Flexion FA values were correlated with SCA in C4/5 (R2 = .211, P = .003), C5/6 (R2 = .454, P < .001), and C6/7 (R2 = .383, P < .001) while flexion ADC values were correlated with SCA in the C4/5 (R2 = .178, P = .006), C5/6 (R2 = .388, P < .001) and C6/7 segments (R2 = .187, P = .005). CONCLUSION: The DTI parameters were correlated with the flexion Cobb angle and the SCA. These data support the dynamic cervical flexion compression hypothesis and indicate that the degree of SCA may be used to assess the condition of HD patients quantitatively.
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BACKGROUND: The mechanism by which Meishan (MS) sows are superior to white crossbred sows in ovarian follicle development remains unclear. Given gut microbiota could regulate female ovarian function and reproductive capacity, this study aimed to determine the role of gut microbiota-ovary axis on follicular development in sows. METHODS: We compared the ovarian follicular development, gut microbiota, plasma metabolome, and follicular fluid metabolome between MS and Landrace × Yorkshire (L × Y) sows. A H2O2-induced cell apoptosis model was used to evaluate the effects of multi-omics identified metabolites on the apoptosis of porcine ovarian granulosa cells in vitro. RESULTS: Compared with L × Y sows, MS sows have greater ovary weight and improved follicular development, including the greater counts of large follicles of diameter ≥ 5 mm, secondary follicles, and antral follicles, but lesser atretic follicles. The ovarian granulosa cells in MS sows had alleviated apoptosis, which was indicated by the increased BCL-2, decreased caspases-3, and decreased cleaved caspases-3 than in L × Y sows. The ovarian follicular fluid of MS sows had higher concentrations of estradiol, progesterone, follicle-stimulating hormone, luteinizing hormone, and insulin like growth factor 1 than L × Y sows. Gut microbiota of MS sows formed a distinct cluster and had improved alpha diversity, including increased Shannon and decreased Simpson than those of L × Y sows. Corresponding to the enhanced function of carbohydrate metabolism and elevated short-chain fatty acids (SCFAs) in feces, the differential metabolites in plasma between MS and L × Y sows are also mainly enriched in pathways of fatty acid metabolism. There were significant correlations among SCFAs with follicular development, ovarian granulosa cells apoptosis, and follicular fluid hormones, respectively. Noteworthily, compared with L × Y sows, MS sows had higher follicular fluid SCFAs concentrations which could ameliorate H2O2-induced porcine granulosa cells apoptosis in vitro. CONCLUSION: MS sows have more secondary and antral follicles, but fewer atretic follicles and apoptotic ovarian granulosa cells, as well as harbored a distinctive gut microbiota than L × Y sows. Gut microbiota may participate in regulating ovarian follicular development via SCFAs affecting granulosa cells apoptosis in sows.
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BACKGROUND/AIM: This research investigated the biophysical properties, safety, and efficacy of polydioxanone (PDO) filler compared to poly-L-lactic acid (PLLA), polycaprolactone (PCL), and hyaluronic acid (HA) fillers. In both mouse and human skin models, a novel collagen stimulation was compared with hyaluronic acid filler. MATERIALS AND METHODS: An electron microscope was used to capture images of the solid particle microsphere shape. Moreover, animal models named SKH1-Hrhr were used to assess the 12-week persistence of PDO, PLLA, or PCL filler. H&E and Sirus Red staining were used to compare collagen density. Five participants in the clinical trial received three injections in the dermis over an eight-month period. Skin density, wrinkles, and gloss were evaluated using DUB® skin scanner, Antera 3D CS, Mark-Vu, and Skin gloss meter after injection to assess the efficacy of fillers. RESULTS: PDO microspheres had uneven surfaces and were spherical and consistent in size. In comparison to other fillers, the PDO filler demonstrated complete biodegradability in just 12 weeks and better neocollagenesis, and a lower inflammatory response than the HA filler. After three injections, the human body assay showed a significant improvement in skin gloss, wrinkles, and density. CONCLUSION: In comparison to PCL and PLLA, PDO filler demonstrated a comparable volume increase rate and better biodegradability. Furthermore, although its physical characteristics are similar to those of a solid, PDO has the advantage of being more organically spread. In photoaging mice, PDO fillers are thought to offer equivalent or superior anti-wrinkle and anti-aging effects to PBS, PCL, and PLLA.
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Preenchedores Dérmicos , Humanos , Camundongos , Animais , Preenchedores Dérmicos/efeitos adversos , Ácido Hialurônico , Pele , Modelos Animais de Doenças , ColágenoRESUMO
This study aimed to investigate the effects of multiple mixing ratio pairs of Saccharomyces cerevisiae (SC) and Clostridium butyricum (CB) on rumen fermentation and growth performance of goats in hot summer. Thirty goats were divided into five groups: 0.00% probiotics (control), 0.30% SC and 0.05% CB (P1), 0.30% SC and 0.10% CB (P2), 0.60% SC and 0.05% CB (P3), and 0.60% SC and 0.10% CB (P4) of the dry matter (DM) weight of the basal diet and were assigned to a 5 × 5 Latin square experimental design. The results showed the pH values, the activities of ruminal cellulolytic enzymes, and the concentrations of ammonia nitrogen, acetic acid, propionic acid, total volatile fatty acids, vitamins B1 and B2, and niacin were significantly increased (p < 0.05) by probiotics. Moreover, the DM intake, average daily gain, the digestibilities of DM, neutral detergent fiber, and acid detergent fiber were significantly increased (p < 0.05) in probiotic-supplemented groups. Additionally, among all probiotic supplementation groups, the P3 group had the most beneficial effect on rumen fermentation parameters and the growth performance of goats. These results suggested that the mixture of 0.60% Saccharomyces cerevisiae and 0.05% Clostridium butyricum of the DM concentration was beneficial to improve rumen fermentation and promote the growth of goats in hot summer.
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To reveal the nature of thermal aggregation of soybean protein at subunit level, structure and physicochemical properties of αα'- and ß-subunits isolated from ß-conglycinin, acidic polypeptide, and basic polypeptide from glycinin, as well as ß-conglycinin and glycinin, were characterized before and after heat treatment. The transmission electron microscopy (TEM) images showed that ß-conglycinin, αα'-subunits and acidic polypeptide formed regular thermal aggregates, which exhibited high solubility, high ζ-potential value, and small particle size. While glycinin, ß-subunit, and basic polypeptide aggregated to insoluble clusters with large particle size distribution. The results of size exclusion chromatography and non-reducing electrophoresis showed that the disulfide bond was the important force in stabilizing the protein conformation of thermal aggregates in ß-conglycinin, glycinin, and their isolated subunits/polypeptides but ß-subunit. The results of surface hydrophobicity and intrinsic fluorescence spectra showed that the thermal aggregations of ß-subunit and basic polypeptide were mainly driven by hydrophobic interactions.
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Globulinas , Proteínas de Soja , Proteínas de Soja/química , Temperatura Alta , Globulinas/química , Proteínas de Armazenamento de Sementes/química , Antígenos de Plantas/química , Peptídeos , Interações Hidrofóbicas e Hidrofílicas , Conformação Proteica , Glycine max/químicaRESUMO
BACKGROUND: Job burnout has become a widespread phenomenon in school settings. However, little is known about the mental health condition of the growing cohort of generalist teachers in rural primary schools. Drawing on the job demands-resource model and social exchange theory, this study examines the correlation between job burnout and job satisfaction through perceived organizational support and work engagement. METHODS: We recruited 639 Chinese generalist teachers in rural primary schools as the study subjects and developed a serial mediation model to assess the hypothesized construct. The data acquired online via Wenjuanxing Software were confirmed as valid and analyzed with SPSS and SmartPLS. RESULTS: The participants scored above the median in perceived organizational support, work engagement, and job satisfaction, and had scores close to the median for job burnout. Statistically significant differences among the investigated variables were found in gender, age, experience, and degree. Job burnout was negatively predictive of perceived organizational support, work engagement, and job satisfaction (each p = 0.000). Perceived organizational support mediated the association between job burnout and work engagement (p = 0.000) and the connection between job burnout and job satisfaction (p = 0.000), while work engagement mediated the association between job burnout and job satisfaction (p = 0.000) and the association between perceived organizational support and job satisfaction (p = 0.000). CONCLUSIONS: Perceived organizational support and work engagement as two sequential mediators buffered the detrimental impact of job burnout on job satisfaction among Chinese generalist teachers in rural primary schools. Targeted strategies should be implemented to diminish generalist teachers' feelings of burnout, being unsupported by organizations, disengagement at work, and dissatisfaction with the job.
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Esgotamento Profissional , Satisfação no Emprego , Humanos , Esgotamento Profissional/epidemiologia , Esgotamento Profissional/psicologia , Engajamento no Trabalho , China , Instituições AcadêmicasRESUMO
This study aimed to investigate the effects of Saccharomyces cerevisiae on rumen fermentation and the growth performance of heat-stressed goats. The fermentation experiment was conducted using Saccharomyces cerevisiae added at 0‱ (HS1), 0.30‱ (SC1), 0.60‱ (SC2), and 1.20‱ (SC3) of the dry matter (DM) weight of the basal diet. The results showed that supplementing with 0.60‱ (SC2) could increase the pH, acetic acid to propionic acid ratio, the concentrations of ammonia nitrogen, total volatile fatty acids, acetic acid, propionic acid, butyric acid, and the degradability of DM, neutral detergent fiber, and acid detergent fiber in rumen fluids of heat-stressed goats. In the feeding experiment, twelve heat-stressed goats were assigned to a 4 × 4 Latin square experimental design, and the Saccharomyces cerevisiae supplement levels are similar to the fermentation experiment above. Similar effects on rumen fermentation and digestibility parameters were obtained with a supplement with 0.60‱ of Saccharomyces cerevisiae (SC2A) compared to the fermentation trial. Moreover, in the SC2A group, the DM intake and average daily gain also increased significantly compared with other groups. These results suggested that a low dose of Saccharomyces cerevisiae can still effectively improve the rumen fermentation and growth performance of heat-stressed goats.
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Objective: Anterior cervical discectomy and fusion (ACDF) surgery can effectively prevent disease progression in patients with Hirayama disease (HD) and diffusion tensor imaging (DTI) can quantitatively assess spinal cord function. In this study, we aimed to evaluate the relationship between preoperative spinal DTI indices and the clinical outcomes of patients with HD when treated by ACDF. Methods: We retrospectively analyzed 35 HD patients treated by ACDF. We collated a range of DTI indices, including fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values, prior to surgery with patients in flexion and neutral positions. Patients were divided into improvement (Im) group and non-improvement (Nim) group according to the Odom score, and the difference in surgical outcomes between the two groups was confirmed by quick disabilities of the arm, shoulder and hand (Q-DASH) scores. The DTI indices in the two groups of patients were then compared. Receiver operating characteristic (ROC) curves and area under curve (AUC) were used to evaluate the predictive capability. The correlation between Q-DASH scores and DTI indices was also evaluated. Results: The FA values in the two groups of patients differed significantly in the cervical flexion position and the different segments were mainly located in the lower cervical spinal cord including the flexion C5/6 (Im group vs. Nim group: 0.501 ± 0.078 vs. 0.362 ± 0.087, P < 0.001) and C6/7 (Im group vs. Nim group: 0.455 ± 0.097 vs. 0.347 ± 0.102, P = 0.003) FA values, the mean FA value for C4/5-C6/7 (Im group vs. Nim group: 0.471 ± 0.067 vs. 0.372 ± 0.078, P < 0.001), mean FA value for C5/6-C6/7 (Im group vs. Nim group: 0.478 ± 0.076 vs. 0.354 ± 0.083, P < 0.001) and mean FA value for the two minimal segments (Im group vs. Nim group: 0.442 ± 0.078 vs. 0.341 ± 0.081, P = 0.001). The ADC values were similar to FA values. The ROC curve for DTI indices in the lower cervical spinal cord had an AUC > 0.7 including: flexion FA value and ADC value for C5/6 (0.877 and 0.931), flexion FA value and ADC value for C6/7 (0.778 and 0.761), flexion mean FA value and ADC value for C4/5-C6/7 (0.846 and 0.859), flexion mean FA value and ADC value for C5/6-C6/7 (0.861 and 0.905), flexion mean FA value and ADC value for the two minimal/maximal segments (0.815 and 0.892). DTI indices including FA value and ADC value were correlated with the preoperative score, final follow-up score and improvement percentage. Flexion ADC value was correlated with improvement score but flexion FA value was not correlated with improvement score. Conclusion: Preoperative DTI indices of the spinal cord, especially those of the lower cervical spinal cord with patients in the flexion position, can predict the clinical outcome of patients with HD post-surgery. In general, a larger FA value and a smaller ADC value indicate a better surgical outcome.
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Pyroptosis is a cell death pathway that plays a significant role in lung adenocarcinoma (LUAD). Also, studies regarding the correlation between the expression of long non-coding RNAs (lncRNAs) and the mechanism of LUAD has aroused concern around the world. The purpose of this paper is to explore the underlying relationship of differentially expressed lncRNAs and pyroptosis-related genes. The least absolute shrinkage and selection operator (LASSO) algorithm and Cox regression were applied to construct a prognostic risk score model from the TCGA database. A pyroptosis-related five-lncRNA signature (CRNDE, HHLA3, MIR193BHG, LINC00941, LINC01843) was considered to be correlated to the prognosis and immune response of LUAD patients. In addition, the cytological experiments revealed that aberrantly expressed HHLA3 displayed a proliferation promotion role in LUAD cells A549 and H460. Next, the forest and nomogram plots have shown this lncRNA signature could be served as an independent prognostic factor for LUAD. The ROC curves further identified the prognostic value of the five-lncRNA signature. The infiltration of immune cells, such as T cells CD8, T cells CD4 memory resting, T cells CD4 memory activated and M0 macrophages were greatly different between the high-risk group and the low-risk group. It implicated that the signature is significantly effective in immunotherapy of LUAD patients. This study has supplied a novel pyroptosis-related lncRNA signature and provided a predictive model for prognosis and immune response of LUAD patients.
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Adenocarcinoma , Neoplasias Pulmonares , RNA Longo não Codificante , Biomarcadores Tumorais , Perfilação da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Pulmão , Prognóstico , PiroptoseRESUMO
The aim of this study was to investigate the influence of the exogenous gut microbiome at early life stages on the development of mice skeletal muscle in adulthood. First, the characteristics of skeletal muscle and the gut microbiota composition of the gut microbiota donorsErhualian (EH) pigs (a native Chinese breed)were studied. EH pigs had significantly higher fiber densities and thinner fiber diameters than Duroc × Landrace × Yorkshire crossed (DLY) pigs (p < 0.05). The expression levels of genes related to oxidized muscle fibers, mitochondrial function, and glucose metabolism in the skeletal muscle of EH pigs were significantly higher than those in DLY pigs (p < 0.05). Moreover, the abundances of 8 gut microbial phyla and 35 genera correlated with the skeletal muscle fiber diameters and densities exhibited significant differences (p < 0.05) between EH and DLY pigs. Subsequently, newborn mice were treated with saline (CG) and fecal microbiota suspensions collected from EH pigs (AG), respectively, for 15 days, starting from the day of birth. In adulthood (60 days), the relative abundances of Parabacteroides, Sutterella, and Dehalobacterium were significantly higher in the feces of the AG mice than those of the CG mice. The microbes contribute to improved functions related to lipid and carbohydrate metabolism. The weight, density, and gene expression related to the oxidized muscle fibers, mitochondrial function, and glucose metabolism of the AG group were significantly higher than those of the CG group (p < 0.05), whereas the fiber diameters in the skeletal muscle of the AG mice were significantly lower (p < 0.05) than those of the CG mice. These results suggested that intervention with exogenous microbiota at early stages of life can affect the fiber size and energy metabolism of their skeletal muscle.
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Objective: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 (SGLT-2) inhibitors reduce glycaemia and weight and improve insulin resistance (IR) via different mechanisms. We aim to evaluate and compare the ability of GLP-1 RAs and SGLT-2 inhibitors to ameliorate the IR of nonalcoholic fatty liver disease (NAFLD) patients. Data Synthesis: Three electronic databases (Medline, Embase, PubMed) were searched from inception until March 2021. We selected randomized controlled trials comparing GLP-1 RAs and SGLT-2 inhibitors with control in adult NAFLD patients with or without T2DM. Network meta-analyses were performed using fixed and random effect models, and the mean difference (MD) with corresponding 95% confidence intervals (CI) were determined. The within-study risk of bias was assessed with the Cochrane collaborative risk assessment tool RoB. Results: 25 studies with 1595 patients were included in this network meta-analysis. Among them, there were 448 patients, in 6 studies, who were not comorbid with T2DM. Following a mean treatment duration of 28.86 weeks, compared with the control group, GLP-1 RAs decreased the HOMA-IR (MD [95%CI]; -1.573[-2.523 to -0.495]), visceral fat (-0.637[-0.992 to -0.284]), weight (-2.394[-4.625 to -0.164]), fasting blood sugar (-0.662[-1.377 to -0.021]) and triglyceride (- 0.610[-1.056 to -0.188]). On the basis of existing studies, SGLT-2 inhibitors showed no statistically significant improvement in the above indicators. Compared with SGLT-2 inhibitors, GLP-1 RAs decreased visceral fat (-0.560[-0.961 to -0.131]) and triglyceride (-0.607[-1.095 to -0.117]) significantly. Conclusions: GLP-1 RAs effectively improve IR in NAFLD, whereas SGLT-2 inhibitors show no apparent effect. Systematic Review Registration: PROSPERO https://www.crd.york.ac.uk/PROSPERO/, CRD42021251704.
Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Inibidores do Transportador 2 de Sódio-Glicose , Adulto , Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeo 1 Semelhante ao Glucagon , Humanos , Metanálise em Rede , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , TriglicerídeosRESUMO
BACKGROUND: To clarify the role of the extension region on the structure-functional relationship of the α-subunit of ß-conglycinin, α-subunit and its segment of the core region (αc-subunit) were expressed via an Escherichia coli system. Their physicochemical properties were compared under acid, neutral or alkaline conditions (pH 4.0, 7.0, and 8.0) and high or low ionic strength (µ = 0.05 and 0.5), respectively. RESULTS: The results showed that the extension region contributed to increasing thermal stability, especially at low ionic strength under acidic and neutral conditions. The extension region stabilized the α-subunit with high solubility, low turbidity, and small particle size under neutral and alkaline conditions, whereas these impacts were suppressed at a high ionic strength and acidic conditions. Surface hydrophobicity of the α-subunit decreased under acidic and alkaline conditions without being interfered with by ionic strength. CONCLUSION: It can be concluded that the extension region played different roles under different pH and ionic strength conditions. These factors should be specified carefully and speculated individually to explore the more detailed and profound nature of ß-conglycinin at the submolecular level. The results could benefit a better understanding of the relationship between domain structure and functions of soybean protein. © 2022 Society of Chemical Industry.