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1.
J Environ Sci (China) ; 148: 375-386, 2025 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-39095172

RESUMO

Tuojiang River Basin is a first-class tributary of the upper reaches of the Yangtze River-which is the longest river in China. As phytoplankton are sensitive indicators of trophic changes in water bodies, characterizing phytoplankton communities and their growth influencing factors in polluted urban rivers can provide new ideas for pollution control. Here, we used direct microscopic count and environmental DNA (eDNA) metabarcoding methods to investigate phytoplankton community structure in Tuojiang River Basin (Chengdu, Sichuan Province, China). The association between phytoplankton community structure and water environmental factors was evaluated by Mantel analysis. Additional environmental monitoring data were used to pinpoint major factors that influenced phytoplankton growth based on structural equation modeling. At the phylum level, the dominant phytoplankton taxa identified by the conventional microscopic method mainly belonged to Bacillariophyta, Chlorophyta, and Cyanophyta, in contrast with Chlorophyta, Dinophyceae, and Bacillariophyta identified by eDNA metabarcoding. In α-diversity analysis, eDNA metabarcoding detected greater species diversity and achieved higher precision than the microscopic method. Phytoplankton growth was largely limited by phosphorus based on the nitrogen-to-phosphorus ratios > 16:1 in all water samples. Redundancy analysis and structural equation modeling also confirmed that the nitrogen-to-phosphorus ratio was the principal factor influencing phytoplankton growth. The results could be useful for implementing comprehensive management of the river basin environment. It is recommended to control the discharge of point- and surface-source pollutants and the concentration of dissolved oxygen in areas with excessive nutrients (e.g., Jianyang-Ziyang). Algae monitoring techniques and removal strategies should be improved in 201 Hospital, Hongrihe Bridge and Colmar Town areas.


Assuntos
Monitoramento Ambiental , Fitoplâncton , Rios , Rios/química , China , Poluentes Químicos da Água/análise , Fósforo/análise
2.
World J Cardiol ; 16(9): 546-549, 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39351336

RESUMO

Tumour immunotherapy represented by immune checkpoint inhibitors (ICIs) has greatly improved the overall prognosis of patients with malignant tumours, and is regarded as an important breakthrough in the field of medicine in recent years. ICIs have gradually become the core of tumour therapy and are increasingly used in the clinic. In order to achieve early clinical prediction and management of immune-related adverse events (irAEs), it is still necessary to perform further research on the mechanisms, risk factors, and predictors of irAE occurrence in the future. Zhou et al describe the consultation of a patient with advanced gastric cancer combined with chronic plaque psoriasis. This case provides an important reference for the use of programmed cell death protein-1 (PD-1) inhibitors in patients of tumours combined with chronic plaque psoriasis. This case also highlights that screening of high-risk groups for irAEs is critical before applying PD-1 inhibitors to patients with chronic psoriasis combined with tumours. PD-1 inhibitors are new and potent antineoplastic agents that can cause serious immune-related adverse events such as toxic epidermal necrolysis release and psoriasis. Glucocorticosteroids are the first-line agents for irAEs. The incidence of rheumatic irAEs may be higher in reality, which will inevitably become a new challenge for rheumatologists and dermatologists.

3.
Elife ; 132024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39352734

RESUMO

The prevailing opinion emphasizes fronto-parietal network (FPN) is key in mediating general fluid intelligence (gF). Meanwhile, recent studies show that human MT complex (hMT+), located at the occipito-temporal border and involved in 3D perception processing, also plays a key role in gF. However, the underlying mechanism is not clear, yet. To investigate this issue, our study targets visuo-spatial intelligence, which is considered to have high loading on gF. We use ultra-high field magnetic resonance spectroscopy (MRS) to measure GABA/Glu concentrations in hMT+ combining resting-state fMRI functional connectivity (FC), behavioral examinations including hMT+ perception suppression test and gF subtest in visuo-spatial component. Our findings show that both GABA in hMT+ and frontal-hMT+ functional connectivity significantly correlate with the performance of visuo-spatial intelligence. Further, serial mediation model demonstrates that the effect of hMT+ GABA on visuo-spatial gF is fully mediated by the hMT+ frontal FC. Together our findings highlight the importance in integrating sensory and frontal cortices in mediating the visuo-spatial component of general fluid intelligence.


Assuntos
Lobo Frontal , Inteligência , Imageamento por Ressonância Magnética , Ácido gama-Aminobutírico , Humanos , Lobo Frontal/fisiologia , Lobo Frontal/diagnóstico por imagem , Masculino , Ácido gama-Aminobutírico/metabolismo , Inteligência/fisiologia , Feminino , Adulto Jovem , Adulto , Espectroscopia de Ressonância Magnética/métodos , Percepção Espacial/fisiologia
4.
Neuropharmacology ; : 110175, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39357738

RESUMO

Methamphetamine (METH) has been implicated in inducing memory impairment, but the precise mechanisms underlying this effect remain unclear. Current research often limits itself to singular models or focuses on individual gene or protein functions, which hampers a comprehensive understanding of the underlying mechanisms. In this study, we established three METH mouse exposure models, extracted hippocampal nuclei, and utilized RNA sequencing to analyze changes in mRNA expression profiles. Our results indicate that METH significantly impairs the learning and memory capabilities of mice. Additionally, we observed that METH-induced inflammatory responses occur in the early phase and do not further exacerbate with repeated injections. However, RNA sequencing revealed the persistent enrichment of inflammatory pathway molecules, which correlated with worsened behaviors. This suggests that although METH-induced neuroinflammation plays a critical role in learning and memory impairment, the continued enrichment of inflammatory pathway molecules is associated with behavioral outcomes. These findings provide crucial evidence for the potential application of immune intervention in METH-related disorders.

7.
Small Methods ; : e2401084, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39351802

RESUMO

Flexible Cu2ZnSn(S,Se)4 (CZTSSe) solar cells is attracting much attention because of their enormous application prospects. However, current flexible CZTSSe solar cells with Mo foil as substrate still suffer from severe back interface problems due to the complexity of substrate surfaces. Herein, a facile approach to tailor the surface of the flexible substrate and modify the back interface between CZTSSe and Mo foil is proposed. The study discloses that a simple polishing can not only improve the wettability of the precursor solution on the substrate unexpectedly and thus improve the quality of the CZTSSe film, but also increase the mechanical stability of the absorber layer grown on Mo foil. The subsequent UV-ozone treatment helps to form a favorite MoO3 layer for efficient CZTSSe devices. Surprisingly, the quasi-ohmic contact is formed between CZTSSe/Mo foil by such combined treatments and thus promoting the carrier collection. Consequently, the efficiency of the flexible CZTSSe solar cell is significantly improved from 4.94% to 10.32% without anti-reflection layer. The bending durability of the cell fabricated on the treated Mo foil is increased greatly. This work discloses that back contact interface is very important for the carrier collection and thus the highly efficient flexible thin film solar cells.

8.
BMC Womens Health ; 24(1): 544, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39354424

RESUMO

OBJECTIVE: To exploit the combination diagnostic performance of serum microRNA-134-5p (miR-134-5p) and color Doppler ultrasound in patients with endometriosis patients. METHODS: Quantitative real time polymerase chain reaction (qRT-PCR) analysis was applied to measure relative abundance of miR-134-5p in serum of patients with endometriosis and gynecological benign diseases. Calculation of uterine artery blood flow parameters was conducted using Color Doppler ultrasound. Receiver operating characteristic (ROC) curve was established to evaluate the diagnostic capacity of miR-134-5p and Doppler parameters. Kaplan-Meier method was used for the analysis of recurrence-free survival rate. RESULTS: Compared with the control group, serum miR-134-5p expression was remarkably diminished in endometriosis patients (P < 0.001). End-diastolic velocity (EDV) and peak systolic velocity (PSV) were notably decreased in endometriosis patients compared with the control group (P < 0.001), while pulsatility index (PI) and resistance index (RI) were distinctly increased (P < 0.001). Serum miR-134-5p expression was positively correlated with EDV (r = 0.5777, P < 0.0001) and PSV (r = 0.6945, P < 0.0001), but negatively correlated with PI (r=-0.6382, P < 0.0001) and RI (r=-0.6247, P < 0.0001). The area under the ROC curve (AUC) of serum miR-134-5p combined with Doppler parameters was 0.905, with the sensitivity of 87.40%, and the specificity of 82.29%. The recurrence-free survival time was shorter in patients with low miR-134-5p expression than those with high miR-134-5p expression (P = 0.013). CONCLUSION: A better diagnostic value of endometriosis detection could be obtained when serum miR-134-5p was combined with Doppler parameters.


Assuntos
Endometriose , MicroRNAs , Ultrassonografia Doppler em Cores , Artéria Uterina , Humanos , Feminino , MicroRNAs/sangue , Ultrassonografia Doppler em Cores/métodos , Adulto , Endometriose/sangue , Endometriose/diagnóstico por imagem , Artéria Uterina/diagnóstico por imagem , Curva ROC , Velocidade do Fluxo Sanguíneo/fisiologia , Estudos de Casos e Controles , Biomarcadores/sangue , Relevância Clínica
9.
BMC Musculoskelet Disord ; 25(1): 766, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39354426

RESUMO

BACKGROUND: The purpose of this study was to evaluate the advantages of robot navigation system-assisted intramedullary nail treatment for humeral shaft fractures and compare it's efficacy with that of traditional surgical intramedullary nail treatment. MATERIALS AND METHODS: This was a retrospective analysis of patients with humeral shaft fractures who received intramedullary nail treatment at our centre from March 2020 to September 2022. The analysis was divided into a robot group and a traditional surgical group on the basis of whether the surgery involved a robot navigation system. We compared the baseline data (age, sex, cause of injury, fracture AO classification, and time of injury-induced surgery), intraoperative conditions (surgery time, length of main nail insertion incision, postoperative fluoroscopy frequency, intraoperative bleeding), fracture healing time, and shoulder joint function at 1 year postsurgery (ASES score and Constant-Murley score) between the two groups of patients. RESULTS: There was no statistically significant difference in the baseline data or average fracture healing time between the two groups of patients. However, the robotic group had significantly shorter surgical times, longer main nail incisions, fewer intraoperative fluoroscopies, and less intraoperative blood loss than did the traditional surgery group (P < 0.001). CONCLUSION: Robot navigation system-assisted intramedullary nail fixation for humeral shaft fractures is a reasonable and effective surgical plan. It can help surgeons determine the insertion point and proximal opening direction faster and more easily, shorten the surgical time, reduce bleeding, avoid more intraoperative fluoroscopy, and enable patients to achieve better shoulder functional outcomes.


Assuntos
Pinos Ortopédicos , Fixação Intramedular de Fraturas , Fraturas do Úmero , Procedimentos Cirúrgicos Robóticos , Humanos , Feminino , Fixação Intramedular de Fraturas/métodos , Fixação Intramedular de Fraturas/instrumentação , Masculino , Estudos Retrospectivos , Fraturas do Úmero/cirurgia , Fraturas do Úmero/diagnóstico por imagem , Adulto , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Robóticos/métodos , Procedimentos Cirúrgicos Robóticos/instrumentação , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Resultado do Tratamento , Consolidação da Fratura , Duração da Cirurgia , Idoso , Cirurgia Assistida por Computador/métodos
10.
Front Endocrinol (Lausanne) ; 15: 1411629, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39355614

RESUMO

Background: Emerging observational studies indicated an association between hyperthyroidism and gastrointestinal disorders. However, it remains unclear whether this association is causal, particularly in the case of gastroesophageal reflux (GERD) and esophageal cancer. Methods: To assess the potential causal relationship between hyperthyroidism and GERD or esophageal cancer, we conducted a bidirectional 2-sample Mendelian randomization study. Independent genetic instruments for hyperthyroidism from the UK Biobank (N case=3,545 and N control=459,388) and public genome-wide association study (GWAS) dataset (N case=3,731 and N control=480,867) were used to investigate the association with esophageal cancer in the UK Biobank study (N case=740 and N control=372,016) and GERD in the public GWAS database (N case=20,381 and N control=464,217). Four different approaches (inverse variance weighted (IVW), weighted mode, MR-Egger, and weighted median regression) were used to ensure that our results more reliable. Additional sensitivity analyses were also performed to validate our results. Results: When hyperthyroidism was considered as the exposure factor, it appeared to act as a protective factor for GERD (ORIVW = 0.88, 95% CI, 0.79-0.99, P = 0.039), while as a risk factor for esophageal cancer (ORIVW = 1.03, 95% CI, 1.01-1.06, P = 0.003). However, there is no evidence supporting a reverse causal relationship between genetic susceptibility to hyperthyroidism and GERD or esophageal cancer. Conclusion: Our findings provided genetic evidence supporting bidirectional causal relationships between hyperthyroidism and GERD or esophageal cancer. These results substantiate certain discoveries from previous observational studies on a causal level and provide insight into relevant genetic susceptibility factors.


Assuntos
Neoplasias Esofágicas , Refluxo Gastroesofágico , Estudo de Associação Genômica Ampla , Hipertireoidismo , Análise da Randomização Mendeliana , Humanos , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/etiologia , Refluxo Gastroesofágico/genética , Refluxo Gastroesofágico/complicações , Refluxo Gastroesofágico/epidemiologia , Hipertireoidismo/genética , Hipertireoidismo/epidemiologia , Hipertireoidismo/complicações , Fatores de Risco , Polimorfismo de Nucleotídeo Único , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Masculino
11.
Artigo em Inglês | MEDLINE | ID: mdl-39361882

RESUMO

While luminescent stimuli-responsive materials (LSRMs) have become one of the most sought-after materials owing to their potential in optoelectronic applications, the use of earth-scarce lanthanides remains a crucial problem to be solved for further development. In this work, two manganese-based LSRMs, (R)-(+)-1-phenylethylammonium manganese bromide, (R-PEA)2MnBr4, and (S)-(-)-1-phenylethylammonium manganese bromide, (S-PEA)2MnBr4, are successfully demonstrated. Both (R-PEA)2MnBr4 and (S-PEA)2MnBr4 show a kinetically stable red-emissive amorphous state and a thermodynamically stable green-emissive crystalline state at room temperature, where the fully reversible transition can be done through melt-quenching and annealing processes. Based on this property, a reusable manganese-halide-based time-temperature indicator is demonstrated for the first time. Furthermore, an X-ray scintillator with a low limit of detection (18.1 nGy/s) and a high spatial resolution limit (30.0 lp/mm) are achieved by exploiting the high transparency of amorphous states. These results uncover the multifunctionality of manganese halides and pave the way for upcoming research.

12.
Sci Rep ; 14(1): 22988, 2024 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-39362925

RESUMO

Tamoxifen (TAM) resistance is a major challenge in treating oestrogen receptor-positive (ER+) breast cancers. It is possible that the H2S synthase cystathionine-γ-lyase (CSE), which has been previously shown to promote tumour growth and metastasis in other cancer cells, is involved in this resistance. Therefore, we investigated CSE's role and potential mechanisms in TAM-resistant breast cancer cells. First, we examined the effect of CSE expression on TAM sensitivity and resistance in MCF7 (breast cancer) cells. The findings revealed that CSE was directly associated with TAM sensitivity and involved in TAM resistance in ER+ breast cancer cells, indicating that it may be useful as a biomarker. Next, we wanted to determine the molecular mechanism of CSE's role in TAM resistance. Using cell migration, co-immunoprecipitation, western blotting, and cell viability assays, we determined that the CSE/H2S system can affect the expression of PPARγ by promoting the sulfhydrylation of PPARγ, which regulates the transcriptional activity of ACSL1. ACSL1, in turn, influences STAT3 activation by affecting the phosphorylation, palmitoylation and dimerization of STAT3, ultimately leading to the development of TAM resistance in breast cancer. Finally, we examined the effect of CSE inhibitors on reducing drug resistance to determine whether CSE may be used as a biomarker of TAM resistance. We observed that the novel CSE inhibitor I194496 can reverse TAM resistance in TAM-resistant breast cancer via targeting the PPARγ/ACSL1/STAT3 signalling pathway. Overall, our data indicate that CSE may serve as a biomarker of TAM resistance and that the CSE inhibitor I194496 is a promising candidate for combating TAM resistance.


Assuntos
Neoplasias da Mama , Cistationina gama-Liase , Resistencia a Medicamentos Antineoplásicos , PPAR gama , Receptores de Estrogênio , Fator de Transcrição STAT3 , Transdução de Sinais , Tamoxifeno , Humanos , Tamoxifeno/farmacologia , Cistationina gama-Liase/metabolismo , Fator de Transcrição STAT3/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , PPAR gama/metabolismo , Feminino , Transdução de Sinais/efeitos dos fármacos , Receptores de Estrogênio/metabolismo , Células MCF-7 , Linhagem Celular Tumoral , Antineoplásicos Hormonais/farmacologia , Movimento Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
13.
Spinal Cord ; 2024 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-39363043

RESUMO

STUDY DESIGN: Bibliometric analysis. OBJECTIVE: To analyze literature on inflammatory expression following spinal cord injury, highlighting development trends, current research status, and potential emerging frontiers. SETTING: Not applicable. METHODS: Articles were retrieved using terms related to spinal cord injury and inflammatory responses from the Web of Science Core Collection, covering January 1, 1980, to May 23, 2024. Tools like CiteSpace and VOSviewer assessed the research landscape, evaluating core authors, journals, and contributing countries. Keyword co-occurrence analyses identified research trends. RESULTS: A total of 2504 articles were retrieved, showing a consistent increase in publications. The Journal of Neurotrauma had the highest publication volume and influence. The most prolific author was Cuzzocrea S, with Popovich PG having the highest H-index. China led in the number of publications, followed closely by the United States, which had the highest impact and extensive international collaboration. Research mainly focused on nerve function recovery, glial scar formation, and oxidative stress. Future research is expected to investigate cellular autophagy, vesicular transport, and related signaling pathways. CONCLUSION: The growing interest in inflammation caused by spinal cord injury is evident, with current research focusing on oxidative stress, glial scar, and neurological recovery. Future directions include exploring autophagy and extracellular vesicles for new therapies. Interdisciplinary research and extensive clinical trials are essential for validating new treatments. Biomarker discovery is crucial for diagnosis and monitoring, while understanding autophagy and signaling pathways is vital for drug development. Global cooperation is needed to accelerate the application of scientific findings, improving spinal cord injury treatment.

14.
Clin Epigenetics ; 16(1): 137, 2024 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-39363385

RESUMO

OBJECTIVE: As the global use of extracorporeal membrane oxygenation (ECMO) treatment increases, survival rates have not correspondingly improved, emphasizing the need for refined patient selection to optimize resource allocation. Currently, prognostic markers at the molecular level are limited. METHODS: Thirty-four cardiogenic shock (CS) patients were prospectively enrolled, and peripheral blood mononuclear cells (PBMCs) were collected at the initiation of ECMO (t0), two-hour post-installation (t2), and upon removal of ECMO (tr). The PBMCs were analyzed by comprehensive epigenomic assays. Using the Wilcoxon signed-rank test and least absolute shrinkage and selection operator (LASSO) regression, 485,577 DNA methylation features were analyzed and selected from the t0 and tr datasets. A random forest classifier was developed using the t0 dataset and evaluated on the t2 dataset. Two models based on DNA methylation features were constructed and assessed using receiver operating characteristic (ROC) curves and Kaplan-Meier survival analyses. RESULTS: The ten-feature and four-feature models for predicting in-hospital mortality attained area under the curve (AUC) values of 0.78 and 0.72, respectively, with LASSO alpha values of 0.2 and 0.25. In contrast, clinical evaluation systems, including ICU scoring systems and the survival after venoarterial ECMO (SAVE) score, did not achieve statistical significance. Moreover, our models showed significant associations with in-hospital survival (p < 0.05, log-rank test). CONCLUSIONS: This study identifies DNA methylation features in PBMCs as potent prognostic markers for ECMO-treated CS patients. Demonstrating significant predictive accuracy for in-hospital mortality, these markers offer a substantial advancement in patient stratification and might improve treatment outcomes.


Assuntos
Metilação de DNA , Oxigenação por Membrana Extracorpórea , Leucócitos Mononucleares , Choque Cardiogênico , Humanos , Oxigenação por Membrana Extracorpórea/métodos , Choque Cardiogênico/terapia , Choque Cardiogênico/genética , Choque Cardiogênico/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Metilação de DNA/genética , Prognóstico , Leucócitos Mononucleares/metabolismo , Biomarcadores/sangue , Idoso , Estudos Prospectivos , Epigenômica/métodos , Curva ROC , Adulto , Mortalidade Hospitalar , Estimativa de Kaplan-Meier , Epigênese Genética
15.
Elife ; 122024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39356105

RESUMO

Euarthropods are an extremely diverse phylum in the modern, and have been since their origination in the early Palaeozoic. They grow through moulting the exoskeleton (ecdysis) facilitated by breaking along lines of weakness (sutures). Artiopodans, a group that includes trilobites and their non-biomineralizing relatives, dominated arthropod diversity in benthic communities during the Palaeozoic. Most trilobites - a hyperdiverse group of tens of thousands of species - moult by breaking the exoskeleton along cephalic sutures, a strategy that has contributed to their high diversity during the Palaeozoic. However, the recent description of similar sutures in early diverging non-trilobite artiopodans means that it is unclear whether these sutures evolved deep within Artiopoda, or convergently appeared multiple times within the group. Here, we describe new well-preserved material of Acanthomeridion, a putative early diverging artiopodan, including hitherto unknown details of its ventral anatomy and appendages revealed through CT scanning, highlighting additional possible homologous features between the ventral plates of this taxon and trilobite free cheeks. We used three coding strategies treating ventral plates as homologous to trilobite-free cheeks, to trilobite cephalic doublure, or independently derived. If ventral plates are considered homologous to free cheeks, Acanthomeridion is recovered sister to trilobites, however, dorsal ecdysial sutures are still recovered at many places within Artiopoda. If ventral plates are considered homologous to doublure or non-homologous, then Acanthomeridion is not recovered as sister to trilobites, and thus the ventral plates represent a distinct feature to trilobite doublure/free cheeks.


Assuntos
Artrópodes , Evolução Biológica , Fósseis , Animais , Artrópodes/anatomia & histologia , Artrópodes/fisiologia , Filogenia , Muda
16.
Insights Imaging ; 15(1): 233, 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39356413

RESUMO

OBJECTIVES: To analyze the lung structure of small airway dysfunction (SAD) defined by spirometry and parametric response mapping (PRM) using high-resolution computed tomography (HRCT), and to analyze the predictive factors for SAD. METHODS: A prospective study was conducted with 388 participants undergoing pulmonary function test (PFT) and inspiratory-expiratory chest CT scans. The clinical data and HRCT assessments of SAD patients defined by both methods were compared. A prediction model for SAD was constructed based on logistic regression. RESULTS: SAD was defined in 122 individuals by spirometry and 158 by PRM. In HRCT visual assessment, emphysema, tree-in-bud sign, and bronchial wall thickening have higher incidence in SAD defined by each method. (p < 0.001). Quantitative CT showed that spirometry-SAD had thicker airway walls (p < 0.001), smaller lumens (p = 0.011), fewer bronchi (p < 0.001), while PRM-SAD had slender blood vessels. Predictive factors for spirometry-SAD were age, male gender, the volume percentage of emphysema in PRM (PRMEmph), tree-in-bud sign, bronchial wall thickening, bronchial count; for PRM-SAD were age, male gender, BMI, tree-in-bud sign, emphysema, the percentage of blood vessel volume with a cross-sectional area less than 1 mm2 (BV1/TBV). The area under curve (AUC) values for the fitted predictive models were 0.855 and 0.808 respectively. CONCLUSIONS: Compared with PRM, SAD defined by spirometry is more closely related to airway morphology, while PRM is sensitive to early pulmonary dysfunction but may be interfered by pulmonary vessels. Models combining patient information and HRCT assessment have good predictive value for SAD. CRITICAL RELEVANCE STATEMENT: HRCT reveals lung structural differences in small airway dysfunction defined by spirometry and parametric response mapping. This insight aids in understanding methodological differences and developing radiological tools for small airways that align with pathophysiology. KEY POINTS: Spirometry-SAD shows thickened airway walls, narrowed lumen, and reduced branch count, which are closely related to airway morphology. PRM shows good sensitivity to early pulmonary dysfunction, although its assessment of SAD based on gas trapping may be affected by the density of pulmonary vessels and other lung structures. Combining patient information and HRCT features, the fitted model has good predictive performance for SAD defined by both spirometry and PRM (AUC values are 0.855 and 0.808, respectively).

17.
Cell Death Dis ; 15(10): 725, 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39358349

RESUMO

Pancreatic cancer is one of the leading causes of cancer-associated mortality, with a poor treatment approach. Previous study has shown that inducing pyroptosis in pancreatic ductal adenocarcinoma (PDAC) slows the growth of PDACs, implying that pyroptosis inducers are potentially effective for PDAC therapy. Here, we found that Dronedarone hydrochloride (DH), an antiarrhythmic drug, induces pyroptosis in pancreatic cancer cells and inhibits PDAC development in mice. In PANC-1 cells, DH caused cell death in a dosage- and time-dependent manner, with only pyroptosis inhibitors and GSDMD silencing rescuing the cell death, indicating that DH triggered GSDMD-dependent pyroptosis. Further work revealed that DH increased mitochondrial stresses and caused mitochondrial DNA (mtDNA) leakage, activating the cytosolic STING-cGAS and pyroptosis pathways. Finally, we assessed the anti-cancer effects of DH in a pancreatic cancer mouse model and found that DH treatment suppressed pancreatic tumor development in vivo. Collectively, our investigation demonstrates that DH triggers pyroptosis in PDAC and proposes its potential effects on anti-PDAC growth.


Assuntos
DNA Mitocondrial , Dronedarona , Neoplasias Pancreáticas , Piroptose , Piroptose/efeitos dos fármacos , Animais , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/genética , Humanos , Dronedarona/farmacologia , DNA Mitocondrial/metabolismo , DNA Mitocondrial/genética , Camundongos , Linhagem Celular Tumoral , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/genética , Camundongos Nus
18.
Nat Commun ; 15(1): 8531, 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39358348

RESUMO

Many mammal species have declining populations, but the consequences of small population size on the genomic makeup of species remain largely unknown. We investigated the evolutionary history, genetic load and adaptive potential of the Cat Ba langur (Trachypithecus poliocephalus), a primate species endemic to Vietnam's famous Ha Long Bay and with less than 100 living individuals one of the most threatened primates in the world. Using high-coverage whole genome data of four wild individuals, we revealed the Cat Ba langur as sister species to its conspecifics of the northern limestone langur clade and found no evidence for extensive secondary gene flow after their initial separation. Compared to other primates and mammals, the Cat Ba langur showed low levels of genetic diversity, long runs of homozygosity, high levels of inbreeding and an excess of deleterious mutations in homozygous state. On the other hand, genetic diversity has been maintained in protein-coding genes and on the gene-rich human chromosome 19 ortholog, suggesting that the Cat Ba langur retained most of its adaptive potential. The Cat Ba langur also exhibits several unique non-synonymous variants that are related to calcium and sodium metabolism, which may have improved adaptation to high calcium intake and saltwater consumption.


Assuntos
Espécies em Perigo de Extinção , Variação Genética , Densidade Demográfica , Animais , Vietnã , Adaptação Fisiológica/genética , Genoma/genética , Filogenia , Cromossomos Humanos Par 19/genética , Homozigoto , Humanos , Fluxo Gênico , Genômica/métodos , Endogamia , Cálcio/metabolismo
19.
mLife ; 3(3): 403-416, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39359674

RESUMO

Prokaryotic Argonautes (pAgos) provide bacteria and archaea with immunity against plasmids and viruses. Catalytically active pAgos utilize short oligonucleotides as guides to directly cleave foreign nucleic acids, while inactive pAgos lacking catalytic residues employ auxiliary effectors, such as nonspecific nucleases, to trigger abortive infection upon detection of foreign nucleic acids. Here, we report a unique group of catalytically active pAgo proteins that frequently associate with a phospholipase D (PLD) family protein. We demonstrate that this particular system employs the catalytic center of the associated PLD protein rather than that of pAgo to restrict plasmid DNA, while interestingly, its immunity against a single-stranded DNA virus relies on the pAgo catalytic center and is enhanced by the PLD protein. We also find that this system selectively suppresses viral DNA propagation without inducing noticeable abortive infection outcomes. Moreover, the pAgo protein alone enhances gene editing, which is unexpectedly inhibited by the PLD protein. Our data highlight the ability of catalytically active pAgo proteins to employ auxiliary proteins to strengthen the targeted eradication of different genetic invaders and underline the trend of PLD nucleases to participate in host immunity.

20.
Front Nutr ; 11: 1424651, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39360285

RESUMO

Background: Minerals play an important role in human health, but their effect on urinary function remains controversial. The aim of this study was to assess the association between dietary intake of minerals (Ca, P, Mg, Fe, Zn, Cu, Na, K, Se) and urine flow rate (UFR). Methods: We conducted a cross-sectional study using the National Health and Nutrition Examination Survey (NHANES, 2009-2018) database. Multivariate regression and smooth curve fitting were used to investigate the association between dietary mineral intakes and UFR. Subgroup analyses and interaction tests were used to investigate whether this association was stable in the population. Results: Our study involving 10,229 representative adult NHANES participants showed an association between Mg intake and UFR in a linear regression model for continuous variables. And in the model analysis of tertile categorical variables, we observed a positive association between six mineral intakes (Ca, Mg, Zn, Cu, Na, and K) and UFR. Smoothed curve fitting and threshold effect analysis further support the nonlinear relationship between mineral intakes and UFR. Subgroup analyses and interaction tests ensured the reliability and robustness of the findings. Conclusion: This study examined the effects of nine dietary minerals on UFR and found that intake of Ca, Mg, Zn, Cu, Na, and K were positively correlated with UFR, suggesting that these minerals may have a positive effect on improving urinary function. In particular, Mg showed a more significant positive correlation with UFR in women, while Na showed a stronger positive correlation in diabetics. However, P, Fe and Se did not show significant correlations. In summary, although these findings provide a preliminary understanding of the relationship between dietary minerals and urinary function, further prospective studies are still necessary to validate these relationships and explore the physiologic mechanisms underlying them.

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