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1.
BMC Musculoskelet Disord ; 25(1): 530, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38987728

RESUMO

PURPOSE: Few studies have focused on the risk factors leading to postoperative blood transfusion after open reduction and internal fixation (ORIF) of proximal humeral fractures (PHFs) in the elderly. Therefore, we designed this study to explore potential risk factors of blood transfusion after ORIF for PHFs. We have also established a nomogram model to integrate and quantify our research results and give feedback. METHODS: In this study, we retrospectively analyzed the clinical data of elderly PHF patients undergoing ORIF from January 2020 to December 2021. We have established a multivariate regression model and nomograph. The prediction performance and consistency of the model were evaluated by the consistency coefficient and calibration curve, respectively. RESULTS: 162 patients met our inclusion criteria and were included in the final study. The following factors are related to the increased risk of transfusion after ORIF: time to surgery, fibrinogen levels, intraoperative blood loss, and surgical duration. CONCLUSIONS: Our patient-specific transfusion risk calculator uses a robust multivariable model to predict transfusion risk.The resulting nomogram can be used as a screening tool to identify patients with high transfusion risk and provide necessary interventions for these patients (such as preoperative red blood cell mobilization, intraoperative autologous blood transfusion, etc.).


Assuntos
Transfusão de Sangue , Fixação Interna de Fraturas , Nomogramas , Redução Aberta , Fraturas do Ombro , Humanos , Idoso , Feminino , Masculino , Fixação Interna de Fraturas/efeitos adversos , Fixação Interna de Fraturas/métodos , Estudos Retrospectivos , Fraturas do Ombro/cirurgia , Idoso de 80 Anos ou mais , Estudos Transversais , Redução Aberta/efeitos adversos , Redução Aberta/métodos , Fatores de Risco , Medição de Risco , Perda Sanguínea Cirúrgica/prevenção & controle
2.
J Am Chem Soc ; 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39019580

RESUMO

Electrocatalysis is generally confined to dynamic liquid-solid and gas-solid interfaces and is rarely applicable in solid-state reactions. Here, we report a paradigm shift strategy to exploit electrocatalysis to accelerate solid-state reactions in the context of lithium-ion batteries (LIBs). We employ heteroatom doping, specifically boron for silicon and sulfur for phosphorus, to catalyze electrochemical Li-alloying reactions in solid-state electrode materials. The preferential cleavage of polar dopant-host chemical bonds upon lithiation triggers chemical bond breaking of the host material. This solid-state catalysis, distinct from liquid and gas phases, requires a critical doping concentration for optimal performance. Beyond a critical concentration of ∼1 atom %, boron and sulfur doping drastically reduces activation energies and accelerates redox kinetics during lithiation/delithiation processes, leading to markedly enhanced rate performance in boron-doped silicon and sulfur-doped black/red phosphorus anode. Notably, a sulfur-doped black phosphorus anode coupled with a lithium cobalt oxide cathode achieves an ultrafast-charging battery, recharging 80% energy of a battery in 302 Wh kg-1 in 9 min, surpassing the thus far reported LIBs.

3.
Huan Jing Ke Xue ; 45(7): 3789-3798, 2024 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-39022927

RESUMO

Guanzhong urban agglomeration has a good development foundation and great development potential, and it has a unique strategic position in the national all-round opening up pattern. In recent years, the problem of near-surface ozone (O3) in the Guanzhong Region has become increasingly prominent, which has become a bottleneck affecting the continuous improvement of air quality. In order to effectively prevent and control O3 pollution, this study analyzed the characteristics of annual, monthly, and daily changes in O3 concentration in the Guanzhong Region based on the environmental monitoring data from 2018 to 2021. A geo-detector was used to study the driving factors of the spatial differentiation of O3 concentration, and the sources of O3 were analyzed using a backward trajectory model and emission inventory construction. The results showed that the daily and monthly variation in O3 concentration in the Guanzhong Region were unimodal. The daily maximum value appeared at 15:00, the minimum value appeared at 07:00, the peak value of the monthly average appeared in June, and the valley value appeared in December. The O3 concentration was highest in summer, followed by that in spring, and the lowest in winter. The days of O3 exceeding the standard showed mainly mild pollution, and moderate and above pollution showed a trend of decreasing first and then increasing. The O3 concentration in the Guanzhong Region was mainly closely related to precursors and meteorological factors, and the explanatory power of the interaction of each factor was significantly greater than that of any single factor. The regional transport of O3 concentration in the Guanzhong Region was mainly affected by easterly airflow, followed by the northwest direction, with the potential source areas located mainly in Henan Province and Hubei Province. The main local sources of volatile organic compounds (VOCs) were solvent use sources, process sources, and mobile sources, and the main emission sources of nitrogen oxides (NOx) were mobile sources and industrial production combustion sources. The research results have a guiding significance for O3 joint prevention and control in the Guanzhong Region.

4.
Int J Biol Macromol ; 275(Pt 2): 133704, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38972655

RESUMO

To identify the key amino acids (AAs) affecting the allergenicity of hemocyanin (HC) allergens from Chinese mitten crabs, in this study, two epitopes, P1-SHFTGSKSNPEQR and P2-LSPGANTITR were employed and four potential key AAs (P1: F3 and N9 and P2: N6 and R10) were predicted. Mast cell and mouse models revealed that four mutants induced lower levels of immunoglobulin E (IgE) and Th2 type cytokines (15.47-49.89 %), proving that F3, N9, N6, and R10 were the key AAs of two epitopes. Mutants reduce allergic responses via the Th2 pathway. However, the roles of every key AA affecting allergenicity were different (P1-F3 > N9 and P2-N6 > R10). In addition, lower transport and higher efflux were observed in the mutants during transport absorption by Caco-2 cells. The allergenicity of HC was stronger when the transport absorption efficiency of epitopes and mutants was higher and their efflux was lower. Our study provides a novel method for revealing the allergenic molecular mechanisms of food allergens.

5.
Ann Intern Med ; 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39008852

RESUMO

BACKGROUND: A major concern has recently emerged about a potential link between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and increased risk for suicidal ideation and behaviors based on International Classification of Diseases codes. OBJECTIVE: To investigate the association between GLP-1 RAs, compared with sodium-glucose cotransporter-2 inhibitors (SGLT2is) or dipeptidyl peptidase-4 inhibitors (DPP4is), and risk for suicidal ideation and behaviors in older adults with type 2 diabetes (T2D). DESIGN: Two target trial emulation studies comparing propensity score (PS)-matched cohorts for GLP-1 RAs versus SGLT2is and GLP-1 RAs versus DPP4is. SETTING: U.S. national Medicare administrative data from January 2017 to December 2020. PATIENTS: Older adults (≥66 years) with T2D; no record of suicidal ideation or behaviors; and a first prescription for a GLP-1 RA, SGLT2i, or DPP4i. MEASUREMENTS: The primary end point was a composite of suicidal ideation and behaviors. New GLP-1 RA users were matched 1:1 on PS to new users of an SGLT2i or DPP4i in each pairwise comparison. A Cox proportional hazards regression was used to estimate the hazard ratio (HR) and 95% CIs within matched groups. RESULTS: This study included 21 807 pairs of patients treated with a GLP-1 RA versus an SGLT2i and 21 402 pairs of patients treated with a GLP-1 RA versus a DPP4i. The HR of suicidal ideation and behaviors associated with GLP-1 RAs relative to SGLT2is was 1.07 (95% CI, 0.80 to 1.45; rate difference, 0.16 [CI, -0.53 to 0.86] per 1000 person-years); the HR relative to DPP4is was 0.94 (CI, 0.71 to 1.24; rate difference, -0.18 [CI, -0.92 to 0.57] per 1000 person-years). LIMITATIONS: Low event rate; imprecise estimates; unmeasured confounders, such as body mass index; and potential misclassification of outcomes. CONCLUSION: Among Medicare beneficiaries with T2D, this study found no clear increased risk for suicidal ideation and behaviors with GLP-1 RAs, although estimates were imprecise and a modest adverse risk could not be ruled out. PRIMARY FUNDING SOURCE: American Foundation for Pharmaceutical Education, Pharmaceutical Research and Manufacturers of America Foundation, National Institute on Aging, and National Institute of Diabetes and Digestive and Kidney Diseases.

6.
MycoKeys ; 106: 287-301, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38993356

RESUMO

Amphichorda has been previously accepted as a member of the Cordycipitaceae and currently it is considered a member of the Bionectriaceae. The substrates of Amphichorda were complex and varied, being mainly animal faeces. This study reports two new species of Amphichorda from Yunnan Province in south-western China. Based on the five-gene (nrSSU, nrLSU, tef-1α, rpb1 and rpb2) sequence and ITS data phylogenetic analysis, two new species, namely A.excrementa and A.kunmingensis, are proposed and a detailed description of the new species is provided. Amphichordaexcrementa and A.kunmingensis were isolated from animal faeces in the park. The morphological characteristics of two novel species and seven known species in Amphichorda are also compared.

7.
iScience ; 27(6): 109931, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38974470

RESUMO

Large prospective studies are required to better elucidate the associations of physical activity, sedentary behaviors (SBs), and sleep with overall cancer and site-specific cancer risk, accounting for the interactions with genetic predisposition. The study included 360,271 individuals in UK Biobank. After a median follow-up of 12.52 years, we found higher total physical activity (TPA) level and higher sleep scores were related to reduced risk of cancer while higher SB level showed a positive association with cancer. Compared with high TPA-healthy sleep group and low SB-healthy sleep group, low TPA-poor sleep group and high SB-poor sleep group had the highest risk for overall cancer, breast cancer, and lung cancer. Adherence to a more active exercise pattern was associated with a lower risk of cancer irrespective of genetic risk. Our study suggests that improving the quality of sleep and developing physical activity habits might yield benefits in mitigating the cancer risk.

8.
Food Chem ; 459: 140339, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38986206

RESUMO

A facile, fast and visible sensing platform for ascorbic acid (AA) detection has been developed based on self-assembled hydrangea-like europium metal-organic framework (HL-EuMOF). HL-EuMOF was synthesized through a simple one-step mixing process with Eu3+ and 1, 10-phenanthroline-2, 9-dicarboxylic acid at room temperature, which exhibited excellent properties including strong red fluorescence, long decay lifetime (548.623 µs) and good luminescent stability. Based on the specific redox reaction between Fe3+ and AA, the HL-EuMOF@Fe3+ was fabricated with "turn-off" response for AA, where the resulting Fe2+ displayed effective fluorescence quenching ability toward HL-EuMOF. The sensor demonstrated low detection limit (31.94 nM), rapid response time (30 s) and high selectivity. Integration of smartphone-assisted RGB analysis with HL-EuMOF@Fe3+ permitted convenient and visible quantitative determination of AA level. This approach also presented good detection performances in complex human serum and beverage samples, which could provide a valuable tool for AA detection in biomedical research and food industry.

9.
Am J Clin Nutr ; 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39029661

RESUMO

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a significant health problem. Dietary intervention plays an important role in patients with MAFLD. OBJECTIVE: We aimed to provide a reference for dietary patterns in patients with MAFLD. METHODS: The presence of MAFLD was determined in the UK Biobank cohort. Nine dietary pattern scores were derived from the dietary records. Multivariable Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). The contrast test was employed to calculate the heterogeneity across MAFLD statuses. RESULTS: We identified 175,300 patients with MAFLD at baseline. Compared with non-MAFLD, MAFLD was significantly associated with chronic liver disease (CLD) (HR: 3.48, 95% CI: 3.15-3.84), severe liver disease (SLD) (HR: 2.87, 95% CI: 2.63-3.14), liver cancer (HR: 1.93, 95% CI: 1.67-2.23), and liver-related death (LRD) (HR: 1.93, 95% CI: 1.67-2.23). In the overall cohort, the alternate Mediterranean diet (aMED) (HRCLD: 0.53, 95% CI: 0.37-0.76; HRSLD: 0.52, 95% CI: 0.37-0.72), Planetary Health Diet (PHD) (HRCLD: 0.62, 95% CI: 0.47-0.81; HRSLD: 0.65, 95% CI: 0.51-0.83) , plant based Low-carbohydrate Diet (pLCD) (HRCLD: 0.65, 95% CI: 0.49-0.86; HRSLD: 0.66, 95% CI: 0.51-0.85), and healthful Plant-based Diet Index (hPDI) (HRCLD: 0.63, 95% CI: 0.47-0.84; HRSLD: 0.61, 95% CI: 0.47-0.78) were associated with a lower risk of CLD and SLD. Additionally, unhealthful Plant-based Diet Index (uPDI) was associated with increased risk of CLD (HR: 1.42, 95% CI: 1.09-1.85), SLD (HR: 1.50, 95% CI: 1.19-1.90), and LRD (HR: 1.88, 95% CI: 1.28-2.78). The aforementioned associations remained consistently strong within the MAFLD subgroup, while exhibiting less pronounced in the non-MAFLD group. However, no significant heterogeneity was observed across different MAFLD statuses. CONCLUSION: These findings highlight the detrimental effects of MAFLD on the development of subsequent liver diseases and the importance of dietary patterns in managing MAFLD.

10.
Ther Apher Dial ; 2024 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-39034285

RESUMO

INTRODUCTION: Peritonitis is a serious complication of peritoneal dialysis (PD), in which insufficient control of antibacterial drug concentrations poses a significant risk for poor outcomes. Predicting antibacterial drug concentrations is crucial in clinical practice. The limitations imposed by compartment models have presented a considerable challenge. METHODS: In this study, we employed machine learning as model-free methods to circumvent the constraints of compartment models. We collected data from 68 observations from 38 patients with peritoneal dialysis-related peritonitis who were treated with vancomycin from the EHR system. This data included information about drug administration, demographic details, and experimental indicators as predictors. We constructed models using Genetic Adaptive Supporting Vector Regression (GA-SVR), KNN-regression, GBM, XGBoost, and a stacking ensemble model. Additionally, we used RMSE loss and partial-dependence profiles to elucidate the effects of these predictors. RESULTS: GA-SVAR outperformed other large-scale models. In 10-fold cross-validation, the RMSE ratio and R-squared values for direct concentration prediction were 23.5% and 0.633, respectively. The ROC AUC for predicting concentrations below 15 and exceeding 20 µg/mL were 0.890 and 0.948, respectively. Notably, the most influential predictors included times of drug administration and weight. These predictors were also influenced by residual kidney function. CONCLUSION: To assist in controlling vancomycin concentrations for patients with PD-related peritonitis in clinical practice, we developed GA-SVR and a corresponding explainer model. Our study improves the controlling of vancomycin in clinical settings by enhancing our understanding of vancomycin concentration in patients with PD-related peritonitis.

12.
Alzheimers Dement ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958394

RESUMO

INTRODUCTION: Sodium-glucose cotransporter 2 (SGLT2) inhibitors exhibit potential benefits in reducing dementia risk, yet the optimal beneficiary subgroups remain uncertain. METHODS: Individuals with type 2 diabetes (T2D) initiating either SGLT2 inhibitor or sulfonylurea were identified from OneFlorida+ Clinical Research Network (2016-2022). A doubly robust learning was deployed to estimate risk difference (RD) and 95% confidence interval (CI) of all-cause dementia. RESULTS: Among 35,458 individuals with T2D, 1.8% in the SGLT2 inhibitor group and 4.7% in the sulfonylurea group developed all-cause dementia over a 3.2-year follow-up, yielding a lower risk for SGLT2 inhibitors (RD, -2.5%; 95% CI, -3.0% to -2.1%). Hispanic ethnicity and chronic kidney disease were identified as the two important variables to define four subgroups in which RD ranged from -4.3% (-5.5 to -3.2) to -0.9% (-1.9 to 0.2). DISCUSSION: Compared to sulfonylureas, SGLT2 inhibitors were associated with a reduced risk of all-cause dementia, but the association varied among different subgroups. HIGHLIGHTS: New users of sodium-glucose cotransporter 2 (SGLT2) inhibitors were significantly associated with a lower risk of all-cause dementia as compared to those of sulfonylureas. The association varied among different subgroups defined by Hispanic ethnicity and chronic kidney disease. A significantly lower risk of Alzheimer's disease and vascular dementia was observed among new users of SGLT2 inhibitors compared to those of sulfonylureas.

13.
PLoS One ; 19(7): e0307517, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39024277

RESUMO

Seaweed fertilizer, formulated primarily with seaweed extract as its main ingredient, has been extensively studied and found to significantly improve nutrient use efficiency, increase crop yield and quality, and enhance soil properties under field conditions. This growing body of evidence shows that seaweed fertilizer is a suitable option for sustainable agriculture in China. However, a comprehensive and quantitative analysis of the overall effects of seaweed fertilizer application in China is lacking. To address this gap, we conducted a meta-analysis of relevant studies on the effects of seaweed fertilizers under field conditions in China with MetaWin and SPSS software. Our analysis examined the effects of seaweed fertilizers on crop yield, quality, and growth under different preparation methods, application techniques, and regions. Our results showed that the application of seaweed fertilizer led to a significant average increase in crop yield of 15.17% compared with the control treatments. Root & tuber crops exhibited the most pronounced response, with a yield boost of 21.19%. Moreover, seaweed fertilizer application significantly improved crop quality, with elevations in the sugar-acid ratio (38.32%) vitamin C (18.07%), starch (19.65%), and protein (11.45%). In addition, plant growth parameters such as height, stem thickness, root weight, and leaf area showed significant enhancement with seaweed fertilizer use. The yield-increasing effect of seaweed fertilizers varied depending on their preparation and use method, climate, and soil of application location. Our study provides fundamental reference data for the efficient and scientific application of seaweed fertilizers in agricultural practices.


Assuntos
Produtos Agrícolas , Fertilizantes , Alga Marinha , Fertilizantes/análise , Alga Marinha/crescimento & desenvolvimento , China , Produtos Agrícolas/crescimento & desenvolvimento , Produção Agrícola/métodos , Agricultura/métodos , Solo/química
14.
Int J Mol Sci ; 25(13)2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-39000250

RESUMO

Beef is a major global source of protein, playing an essential role in the human diet. The worldwide production and consumption of beef continue to rise, reflecting a significant trend. However, despite the critical importance of beef cattle resources in agriculture, the diversity of cattle breeds faces severe challenges, with many breeds at risk of extinction. The initiation of the Beef Cattle Genome Project is crucial. By constructing a high-precision functional annotation map of their genome, it becomes possible to analyze the genetic mechanisms underlying important traits in beef cattle, laying a solid foundation for breeding more efficient and productive cattle breeds. This review details advances in genome sequencing and assembly technologies, iterative upgrades of the beef cattle reference genome, and its application in pan-genome research. Additionally, it summarizes relevant studies on the discovery of functional genes associated with key traits in beef cattle, such as growth, meat quality, reproduction, polled traits, disease resistance, and environmental adaptability. Finally, the review explores the potential of telomere-to-telomere (T2T) genome assembly, structural variations (SVs), and multi-omics techniques in future beef cattle genetic breeding. These advancements collectively offer promising avenues for enhancing beef cattle breeding and improving genetic traits.


Assuntos
Genoma , Animais , Bovinos/genética , Genômica/métodos , Cruzamento/métodos , Sequenciamento Completo do Genoma/métodos , Carne Vermelha , Locos de Características Quantitativas
15.
Sci Total Environ ; 948: 174655, 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39004375

RESUMO

Microplastics (MPs) are widely present in terrestrial ecosystems. However, how MPs impact carbon (C) and nitrogen (N) cycling within plant-soil system is still poorly understood. Here, we conducted a meta-analysis utilizing 3338 paired observations from 180 publications to estimate the effects of MPs on plant growth (biomass, nitrogen content, nitrogen uptake and nitrogen use efficiency), change in soil C content (total carbon (TC), soil organic carbon (SOC), dissolved organic carbon (DOC), microbial biomass carbon (MBC)), C losses (carbon dioxide (CO2) and methane), soil N content (total nitrogen, dissolved organic nitrogen, microbial biomass nitrogen, total dissolve nitrogen, ammonium, nitrate (NO3--N) and nitrite) and nitrogen losses (nitrous oxide, ammonia (NH3) volatilization and N leaching) comprehensively. Results showed that although MPs significantly increased CO2 emissions by 25.7 %, they also increased TC, SOC, MBC, DOC and CO2 by 53.3 %, 25.4 %, 19.6 % and 24.7 %, respectively, and thus increased soil carbon sink capacity. However, MPs significantly decreased NO3--N and NH3 volatilization by 14.7 % and 43.3 %, respectively. Meanwhile, MPs significantly decreased plant aboveground biomass, whereas no significant changes were detected in plant belowground biomass and plant N content. The impacts of MPs on soil C, N and plant growth varied depending on MP types, sizes, concentrations, and experimental durations, in part influenced by initial soil properties. Overall, although MPs enhanced soil carbon sink capacity, they may pose a significant threat to future agricultural productivity.

16.
Nat Commun ; 15(1): 5999, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39013955

RESUMO

Electrocatalytic alkynes semi-hydrogenation to produce alkenes with high yield and Faradaic efficiency remains technically challenging because of kinetically favorable hydrogen evolution reaction and over-hydrogenation. Here, we propose a hierarchically nanoporous Cu50Au50 alloy to improve electrocatalytic performance toward semi-hydrogenation of alkynes. Using Operando X-ray absorption spectroscopy and density functional theory calculations, we find that Au modulate the electronic structure of Cu, which could intrinsically inhibit the combination of H* to form H2 and weaken alkene adsorption, thus promoting alkyne semi-hydrogenation and hampering alkene over-hydrogenation. Finite element method simulations and experimental results unveil that hierarchically nanoporous catalysts induce a local microenvironment with abundant K+ cations by enhancing the electric field within the nanopore, accelerating water electrolysis to form more H*, thereby promoting the conversion of alkynes. As a result, the nanoporous Cu50Au50 electrocatalyst achieves highly efficient electrocatalytic semi-hydrogenation of alkynes with 94% conversion, 100% selectivity, and a 92% Faradaic efficiency over wide potential window. This work provides a general guidance of the rational design for high-performance electrocatalytic transfer semi-hydrogenation catalysts.

17.
Adv Sci (Weinh) ; : e2401492, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38932472

RESUMO

Genetic and epigenetic alterations are cancer hallmark characteristics. However, the role of inherited cancer predisposition alleles in co-opting lineage factor epigenetic reprogramming and tumor progression remains elusive. Here the FinnGen cohort phenome-wide analysis, along with multiple genome-wide association studies, has consistently identified the rs339331-RFX6/6q22 locus associated with prostate cancer (PCa) risk across diverse populations. It is uncovered that rs339331 resides in a reprogrammed androgen receptor (AR) binding site in PCa tumors, with the T risk allele enhancing AR chromatin occupancy. RFX6, an AR-regulated gene linked to rs339331, exhibits synergistic prognostic value for PCa recurrence and metastasis. This comprehensive in vitro and in vivo studies demonstrate the oncogenic functions of RFX6 in promoting PCa cell proliferation and metastasis. Mechanistically, RFX6 upregulates HOXA10 that profoundly correlates with adverse PCa outcomes and is pivotal in RFX6-mediated PCa progression, facilitating the epithelial-mesenchymal transition (EMT) and modulating the TGFß/SMAD signaling axis. Clinically, HOXA10 elevation is associated with increased EMT scores, tumor advancement and PCa recurrence. Remarkably, reducing RFX6 expression restores enzalutamide sensitivity in resistant PCa cells and tumors. This findings reveal a complex interplay of genetic and epigenetic mechanisms in PCa pathogenesis and drug resistance, centered around disrupted prostate lineage AR signaling and abnormal RFX6 expression.

18.
Brain Behav Immun ; 120: 413-429, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38925413

RESUMO

Huntington's disease (HD) is a hereditary neurodegenerative disorder characterized by involuntary movements, cognitive deficits, and psychiatric symptoms. Currently, there is no cure, and only limited treatments are available to manage the symptoms and to slow down the disease's progression. The molecular and cellular mechanisms of HD's pathogenesis are complex, involving immune cell activation, altered protein turnover, and disturbance in brain energy homeostasis. Microglia have been known to play a dual role in HD, contributing to neurodegeneration through inflammation but also enacting neuroprotective effects by clearing mHTT aggregates. However, little is known about the contribution of microglial metabolism to HD progression. This study explores the impact of a microglial metabolite transporter, equilibrative nucleoside transporter 3 (ENT3), in HD. Known as a lysosomal membrane transporter protein, ENT3 is highly enriched in microglia, with its expression correlated with HD severity. Using the R6/2 ENT3-/- mouse model, we found that the deletion of ENT3 increases microglia numbers yet worsens HD progression, leading to mHTT accumulation, cell death, and disturbed energy metabolism. These results suggest that the delicate balance between microglial metabolism and function is crucial for maintaining brain homeostasis and that ENT3 has a protective role in ameliorating neurodegenerative processes.

19.
Medicine (Baltimore) ; 103(26): e38700, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38941382

RESUMO

This study aims to critically reassess existing systematic reviews (SR) on Traditional Chinese Exercises (TCE) for treating Chronic Obstructive Pulmonary Disease (COPD). The primary objectives include synthesizing available evidence, evaluating the methodological quality of reviews and overall evidence, and providing comprehensive insights into the effectiveness of different TCE types in managing COPD. Sinomed, CNKI, VIP, Wanfang, PubMed, Cochrane Library, and Web of Science were searched from inception to April 2023 for SR literature on the treatment of COPD with TCE. The extracted data from the included SRs encompassed various aspects such as general information, study population, intervention measures, meta-analysis results, and conclusions. The methodological quality of the included SRs was assessed using the AMSTAR II tool. Additionally, the GRADE tool was used to determine the evidence level of outcome indicators. This study included 17 SRs and 4 types of TCE. The CCA was 0.041, indicating a slight overlap between the primary studies. Notably, one study was rated as low quality on the AMSTAR II scale, while the rest were classified as critically low quality. The results from the GRADE evaluation revealed 26 pieces of very low-quality evidence, 55 pieces of low-quality evidence, and 17 pieces of moderate-quality evidence. The moderate-quality evidence suggests that Liuzijue effectively improves TCM syndrome scores in patients with COPD. Additionally, low-quality evidence suggests that Liuzijue improves patients' lung function (FEV1, FVC) and quality of life (CAT, MRC/mMRC). Similarly, low-quality evidence suggests that Baduanjin can improve patients' lung function (FEV1%, FVC) and quality of life (SGRQ). Low-quality evidence also suggests that Health Qigong can significantly improve patients' exercise endurance (6MWD). No SR reported TCE-related adverse reactions. TCE interventions are effective and safe in the treatment of COPD. Different types of TCE have varying effects on outcomes in COPD patients. However, these findings are limited by the generally low methodological and evidence quality of the included SRs. Therefore, it is strongly recommended to improve study designs to obtain higher-quality clinical evidence and to strictly follow SR protocols.


Assuntos
Medicina Tradicional Chinesa , Doença Pulmonar Obstrutiva Crônica , Revisões Sistemáticas como Assunto , Doença Pulmonar Obstrutiva Crônica/terapia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/reabilitação , Humanos , Medicina Tradicional Chinesa/métodos , Terapia por Exercício/métodos , Qualidade de Vida , Qigong/métodos , População do Leste Asiático
20.
Neurology ; 103(2): e209502, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-38875513

RESUMO

BACKGROUND AND OBJECTIVES: The Patient-Ranked Order of Function (PROOF) is a novel approach to account for patient-reported preferences in the evaluation of treatments of amyotrophic lateral sclerosis (ALS). In this study, we assess the reliability and prognostic value of different sets of patient-reported preferences that can be used for the PROOF end point. METHODS: Data were obtained through online surveys over the course of 12 months using the population-based registry of the Netherlands. Patients were asked to score functional domains of the ALS Functional Rating Scale (ALSFRS-R) and rank the order of importance of each domain. Two weeks after the initial invite, the questionnaire was repeated to evaluate test-retest reliability. Vital status was extracted from the municipal population register. RESULTS: In total, 611 patients with ALS were followed up for survival and 382 patients were included in the test-retest reliability study. All versions of PROOF, using different sets of preferences, resulted in excellent reliability (intraclass correlation coefficients ranged from 0.89 [95% CI 0.87-0.91] to 0.97 [95% CI 0.97-0.98], all p < 0.001), without systematic differences between baseline and week 2 (mean rank difference range -1 to -3 [95% CI range -8 to 2], all p > 0.20). Preferences about future events were more variable than preferences about current symptoms. All versions of PROOF strongly predicted overall survival (hazard ratios per 10th rank percentile ranged from 0.80 to 0.83 [95% CI range 0.76-0.87], all p < 0.001) and had a more even separation of survival curves between rank-stratified subgroups compared with the ALSFRS-R total score. DISCUSSION: In a large cohort of patients, we show how patient-reported preferences can be measured and integrated reliably with the ALSFRS-R without leading to systematic bias. Patient preferences may provide unique prognostic information in addition to what is already measured conventionally. This could provide a more comprehensive understanding of how medical interventions effectively address the patient's concerns and improve what matters most to them.


Assuntos
Esclerose Lateral Amiotrófica , Preferência do Paciente , Humanos , Esclerose Lateral Amiotrófica/terapia , Esclerose Lateral Amiotrófica/diagnóstico , Esclerose Lateral Amiotrófica/fisiopatologia , Masculino , Feminino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Prognóstico , Idoso , Países Baixos , Ensaios Clínicos como Assunto , Inquéritos e Questionários , Sistema de Registros
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