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1.
Front Pharmacol ; 15: 1348076, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38572428

RESUMO

Cancer stands as a prominent global cause of death. One of the key reasons why clinical tumor chemotherapy fails is multidrug resistance (MDR). In recent decades, accumulated studies have shown how Natural Product-Derived Compounds can reverse tumor MDR. Discovering novel potential modulators to reduce tumor MDR by Natural Product-Derived Compounds has become a popular research area across the globe. Numerous studies mainly focus on natural products including flavonoids, alkaloids, terpenoids, polyphenols and coumarins for their MDR modulatory activity. Natural products reverse MDR by regulating signaling pathways or the relevant expressed protein or gene. Here we perform a deep review of the previous achievements, recent advances in the development of natural products as a treatment for MDR. This review aims to provide some insights for the study of multidrug resistance of natural products.

2.
Biomed Environ Sci ; 37(3): 254-265, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38582990

RESUMO

Objective: Studies on the relationship between iodine, vitamin A (VA), and vitamin D (VD) and thyroid function are limited. This study aimed to analyze iodine and thyroid-stimulating hormone (TSH) status and their possible relationships with VA, VD, and other factors in postpartum women. Methods: A total of 1,311 mothers (896 lactating and 415 non-lactating) from Hebei, Zhejiang, and Guangxi provinces were included in this study. The urinary iodine concentration (UIC), TSH, VA, and VD were measured. Results: The median UIC of total and lactating participants were 142.00 µg/L and 139.95 µg/L, respectively. The median TSH, VA, and VD levels in all the participants were 1.89 mIU/L, 0.44 µg/mL, and 24.04 ng/mL, respectively. No differences in the UIC were found between lactating and non-lactating mothers. UIC and TSH levels were significantly different among the three provinces. The rural UIC was higher than the urban UIC. Obese mothers had a higher UIC and a higher prevalence of excessive TSH. Higher UICs and TSHs levels were observed in both the VD deficiency and insufficiency groups than in the VD-sufficient group. After adjustment, no linear correlation was observed between UIC and VA/VD. No interaction was found between vitamins A/D and UIC on TSH levels. Conclusion: The mothers in the present study had no iodine deficiency. Region, area type, BMI, and VD may be related to the iodine status or TSH levels.


Assuntos
Iodo , Tireotropina , Humanos , Feminino , Estudos Transversais , Lactação , China/epidemiologia , Período Pós-Parto , Estado Nutricional , Vitaminas , Vitamina D , Vitamina A , Colecalciferol
3.
Nano Lett ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38587212

RESUMO

Ghost phonon polaritons (g-PhPs), a unique class of phonon polaritons in the infrared, feature ultralong diffractionless propagation (>20 µm) across the surface and tilted wavefronts in the bulk. Here, we study hybrid g-PhPs in a heterostructure of calcite and an ultrathin film of the phase change material (PCM) In3SbTe2, where the optical field is bound in the PCM film with enhanced confinement compared with conventional g-PhPs. Near-field optical images for hybrid g-PhPs reveal a lemniscate pattern in the momentum distribution. We fabricated In3SbTe2 gratings and investigated how different orientations and periodicities of gratings impact the propagation of hybrid g-PhPs. As the grating period decreases to zero, the wavefront of hybrid g-PhPs can be dynamically steered by varying the grating orientation. Our results highlight the promise of hybrid g-PhPs with tunable functionalities for nanophotonic studies.

4.
Alzheimers Res Ther ; 16(1): 69, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38570794

RESUMO

BACKGROUND: Neuropsychiatric symptoms (NPS) are prevalent in cognitively impaired individuals including Alzheimer's disease (AD) dementia and mild cognitive impairment (MCI). Whereas several studies have reported the associations between NPS with AD pathologic biomarkers and cerebral small vessel disease (SVD), but it remains unknown whether AD pathology and SVD contribute to different sub-syndromes independently or aggravate same symptoms synergistically. METHOD: We included 445 cognitively impaired individuals (including 316 MCI and 129 AD) with neuropsychiatric, cerebrospinal fluid (CSF) biomarkers (Aß42, p-tau, and t-tau) and multi-model MRI data. Psychiatric symptoms were accessed by using the Neuropsychiatric Inventory (NPI). Visual assessment of SVD (white matter hyperintensity, microbleed, perivascular space, lacune) on MRI images was performed by experienced radiologist. Linear regression analyses were conducted to test the association between neuropsychiatric symptoms with AD pathology and CSVD burden after adjustment for age, sex, education, apolipoprotein E (APOE) ε4 carrier status, and clinical diagnosis. RESULTS: The NPI total scores were related to microbleed (estimate 2.424; 95% CI [0.749, 4.099]; P =0.005). Considering the sub-syndromes, the hyperactivity was associated with microbleed (estimate 0.925; 95% CI [0.115, 1.735]; P =0.025), whereas the affective symptoms were correlated to CSF level of Aß42 (estimate -0.006; 95% CI [-0.011, -0.002]; P =0.005). Furthermore, we found the apathy sub-syndrome was associated with CSF t-tau/Aß42 (estimate 0.636; 95% CI [0.078, 1.194]; P =0.041) and microbleed (estimate 0.693; 95% CI [0.046, 1.340]; P =0.036). In addition, we found a significant interactive effect between CSF t-tau/Aß42 and microbleed (estimate 0.993; 95% CI [0.360, 1.626]; P =0.019) on severity of apathy sub-syndrome. CONCLUSION: Our study showed that CSF Aß42 was associated with affective symptoms, but microbleed was correlated with hyperactivity and apathy, suggesting the effect of AD pathology and SVD on different neuropsychiatric sub-syndromes.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Proteínas tau/líquido cefalorraquidiano , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Doença de Alzheimer/patologia , Disfunção Cognitiva/diagnóstico , Biomarcadores/líquido cefalorraquidiano , Fragmentos de Peptídeos/líquido cefalorraquidiano , Hemorragia Cerebral
5.
World J Gastrointest Surg ; 16(3): 807-815, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38577084

RESUMO

BACKGROUND: Ostomy is a common surgery usually performed to protect patients from clinical symptoms caused by distal anastomotic leakage after colorectal cancer (CRC) surgery and perforation or to relieve intestinal obstruction. AIM: To analyze the complications after transverse colostomy closure. METHODS: Patients who underwent transverse colostomy closure from Jan 2015 to Jan 2022 were retrospectively enrolled in a single clinical center. The differences between the complication group and the no complication group were compared. Logistic regression analyses were conducted to find independent factors for overall complications or incision infection. RESULTS: A total of 102 patients who underwent transverse colostomy closure were enrolled in the current study. Seventy (68.6%) patients underwent transverse colostomy because of CRC related causes. Postoperative complications occurred in 30 (29.4%) patients and the most frequent complication occurring after transverse colostomy closure was incision infection (46.7%). The complication group had longer hospital stays (P < 0.01). However, no potential risk factors were identified for overall complications and incision infection. CONCLUSION: The most frequent complication occurring after transverse colostomy closure surgery in our center was incision infection. The operation time, interval from transverse colostomy to reversal, and method of anastomosis might have no impact on the postoperative complications. Surgeons should pay more attention to aseptic techniques.

6.
Sci Total Environ ; : 172202, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38599399

RESUMO

As an emerging atmospheric pollutant, airborne environmentally persistent free radicals (EPFRs) are formed during many combustion processes and pose various adverse health effects. In health-oriented air pollution control, it is vital to evaluate the health effects of atmospheric fine particulate matter (PM2.5) from different emission sources. In this study, various types of combustion-derived PM2.5 were collected on filters in a partial-flow dilution tunnel sampling system from three typical emission sources: coal combustion, biomass burning, and automobile exhaust. Substantial concentrations of EPFRs were determined in PM2.5 samples and associated with significant potential exposure risks. Results from in vitro cytotoxicity and oxidative potential assays suggest that EPFRs may cause substantial generation of reactive oxygen species (ROS) upon inhalation exposure to PM2.5 from anthropogenic combustion sources, especially from automobile exhaust. This study provides important evidence for the source- and concentration-dependent health effects of EPFRs in PM2.5 and motivates further assessments to advance public health-oriented PM2.5 emission control.

7.
J Alzheimers Dis ; 98(3): 897-906, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38461505

RESUMO

Background: Financial capacity is vital for the elderly, who possess a substantial share of global wealth but are vulnerable to financial fraud. Objective: We explored the link between small vessel disease (SVD) and financial capacity in cognitively unimpaired (CU) older adults via both cross-sectional and longitudinal analyses. Methods: 414 CU participants underwent MRI and completed the Financial Capacity Instrument-Short Form (FCI-SF). Subsequent longitudinal FCI-SF data were obtained from 104, 240, and 141 participants at one, two, and four years, respectively. SVD imaging markers, encompassing white matter hyperintensities (WMH), cerebral microbleeds (CMB), and lacune were evaluated. We used linear regression analyses to cross-sectionally explore the association between FCI-SF and SVD severity, and linear mixed models to assess how baseline SVD severity impacted longitudinal FCI-SF change. The false discovery rate method was used to adjust multiple comparisons. Results: Cross-sectional analysis revealed a significant association between baseline WMH and Bank Statement (BANK, ß=-0.194), as well as between lacune number and Financial Conceptual Knowledge (FC, ß= -0.171). These associations were stronger in APOE ɛ4 carriers, with ß= -0.282 for WMH and BANK, and ß= -0.366 for lacune number and FC. Longitudinally, higher baseline SVD total score was associated with severe FCI-SF total score decrease (ß= -0.335). Additionally, baseline WMH burden predicted future decreases in Single Checkbook/Register Task (SNG, ß= -0.137) and FC (ß= -0.052). Notably, the association between baseline WMH and SNG changes was amplified in APOE ɛ4 carriers (ß= -0.187). Conclusions: Severe SVD was associated with worse FCI-SF and could predict the decline of financial capacity in CU older adults.


Assuntos
Doenças de Pequenos Vasos Cerebrais , Doenças Vasculares , Substância Branca , Humanos , Idoso , Estudos Transversais , Imageamento por Ressonância Magnética , Doenças Vasculares/complicações , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Doenças de Pequenos Vasos Cerebrais/genética , Doenças de Pequenos Vasos Cerebrais/complicações , Apolipoproteínas E
8.
J Adv Res ; 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38431123

RESUMO

INTRODUCTION: The growing prevalence of osteoporosis (OP) in an aging global population presents a significant public health concern. Tobacco smoke negatively affects bone turnover, leading to reduced bone mass and heightened OP and fracture risk. However, the impact of early-life tobacco smoke exposure on later-life OP risk remains unclear. OBJECTIVES: This study was to explore the effects of early-life tobacco smoke exposure on incident OP risk in later life. The mediating role of telomere length (TL) and the interaction with genetic predisposition were also studied. METHODS: Data on in utero tobacco smoke exposure (IUTSE) status and age of tobacco use initiation from the UK Biobank were used to estimate early-life tobacco smoke exposure. Incident OP cases were identified according to health-related records. Linear, Cox, and Laplace regression models were mainly used for data analysis. RESULTS: Individuals with IUTSE showed a higher OP risk [hazard ratio (HR): 1.06, 95 % confidence interval (CI): 1.01, 1.11] and experienced earlier OP onset by 0.30 years [50th percentile difference = -0.30, 95 % CI: -0.51, -0.09] compared to those without. Participants initiating tobacco smoke in childhood, adolescence, and adulthood had 1.41 times (95 % CI: 1.23, 1.61), 1.17 times (95 % CI:1.10, 1.24), and 1.14 times (95 % CI: 1.07, 1.20) the risk of OP, respectively, compared to never smokers. They also experienced earlier OP onset by 2.16, 0.95, and 0.71 years, sequentially. The TL significantly mediated the early-life tobacco exposure and OP association. Significant joint and interactive effects were detected between early-life tobacco smoke exposure and genetic elements. CONCLUSIONS: Our findings implicate that early-life tobacco smoke exposure elevates the later-life OP risk, mediated by telomere length and interplayed with genetic predisposition. These findings highlight the importance of early-life intervention against tobacco smoke exposure and ageing status for precise OP prevention, especially in individuals with a high genetic risk.

9.
Brain Commun ; 6(1): fcae033, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38425749

RESUMO

The objectively-defined subtle cognitive decline individuals had higher progression rates of cognitive decline and pathological deposition than healthy elderly, indicating a higher risk of progressing to Alzheimer's disease. However, little is known about the brain functional alterations during this stage. Thus, we aimed to investigate the functional network patterns in objectively-defined subtle cognitive decline cohort. Forty-two cognitive normal, 29 objectively-defined subtle cognitive decline and 55 mild cognitive impairment subjects were included based on neuropsychological measures from the Alzheimer's disease Neuroimaging Initiative dataset. Thirty cognitive normal, 22 objectively-defined subtle cognitive declines and 48 mild cognitive impairment had longitudinal MRI data. The degree centrality and eigenvector centrality for each participant were calculated by using resting-state functional MRI. For cross-sectional data, analysis of covariance was performed to detect between-group differences in degree centrality and eigenvector centrality after controlling age, sex and education. For longitudinal data, repeated measurement analysis of covariance was used for comparing the alterations during follow-up period among three groups. In order to classify the clinical significance, we correlated degree centrality and eigenvector centrality values to Alzheimer's disease biomarkers and cognitive function. The results of analysis of covariance showed significant between-group differences in eigenvector centrality and degree centrality in left superior temporal gyrus and left precuneus, respectively. Across groups, the eigenvector centrality value of left superior temporal gyrus was positively related to recognition scores in auditory verbal learning test, whereas the degree centrality value of left precuneus was positively associated with mini-mental state examination total score. For longitudinal data, the results of repeated measurement analysis of covariance indicated objectively-defined subtle cognitive decline group had the highest declined rate of both eigenvector centrality and degree centrality values than other groups. Our study showed an increased brain functional connectivity in objectively-defined subtle cognitive decline individuals at both local and global level, which were associated with Alzheimer's disease pathology and neuropsychological assessment. Moreover, we also observed a faster declined rate of functional network matrix in objectively-defined subtle cognitive decline individuals during the follow-ups.

10.
Proc Natl Acad Sci U S A ; 121(13): e2308788121, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38507445

RESUMO

Protein structure prediction has been greatly improved by deep learning in the past few years. However, the most successful methods rely on multiple sequence alignment (MSA) of the sequence homologs of the protein under prediction. In nature, a protein folds in the absence of its sequence homologs and thus, a MSA-free structure prediction method is desired. Here, we develop a single-sequence-based protein structure prediction method RaptorX-Single by integrating several protein language models and a structure generation module and then study its advantage over MSA-based methods. Our experimental results indicate that in addition to running much faster than MSA-based methods such as AlphaFold2, RaptorX-Single outperforms AlphaFold2 and other MSA-free methods in predicting the structure of antibodies (after fine-tuning on antibody data), proteins of very few sequence homologs, and single mutation effects. By comparing different protein language models, our results show that not only the scale but also the training data of protein language models will impact the performance. RaptorX-Single also compares favorably to MSA-based AlphaFold2 when the protein under prediction has a large number of sequence homologs.


Assuntos
Anticorpos , Proteínas , Proteínas/genética , Proteínas/química , Anticorpos/genética , Alinhamento de Sequência , Algoritmos
11.
Hum Brain Mapp ; 45(5): e26634, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38553856

RESUMO

Cerebral small vessel disease (SVD) can disrupt the global brain network and lead to cognitive impairment. Conversely, cognitive reserve (CR) can improve one's cognitive ability to handle damaging effects like SVD, partly by optimizing the brain network's organization. Understanding how SVD and CR collectively influence brain networks could be instrumental in preventing cognitive impairment. Recently, brain redundancy has emerged as a critical network protective metric, providing a nuanced perspective of changes in network organization. However, it remains unclear how SVD and CR affect global redundancy and subsequently cognitive function. Here, we included 121 community-dwelling participants who underwent neuropsychological assessments and a multimodal MRI examination. We visually examined common SVD imaging markers and assessed lifespan CR using the Cognitive Reserve Index Questionnaire. We quantified the global redundancy index (RI) based on the dynamic functional connectome. We then conducted multiple linear regressions to explore the specific cognitive domains related to RI and the associations of RI with SVD and CR. We also conducted mediation analyses to explore whether RI mediated the relationships between SVD, CR, and cognition. We found negative correlations of RI with the presence of microbleeds (MBs) and the SVD total score, and a positive correlation of RI with leisure activity-related CR (CRI-leisure). RI was positively correlated with memory and fully mediated the relationships between the MBs, CRI-leisure, and memory. Our study highlights the potential benefits of promoting leisure activities and keeping brain redundancy for memory preservation in older adults, especially those with SVD.


Assuntos
Doenças de Pequenos Vasos Cerebrais , Disfunção Cognitiva , Reserva Cognitiva , Humanos , Idoso , Pessoa de Meia-Idade , Cognição , Encéfalo/diagnóstico por imagem , Disfunção Cognitiva/psicologia , Imageamento por Ressonância Magnética , Doenças de Pequenos Vasos Cerebrais/complicações
12.
Environ Sci Technol ; 58(13): 5739-5749, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38456395

RESUMO

Epidemiological studies have demonstrated the embryonic and developmental toxicity of plasticizers. Thus, understanding the in utero biotransformation and accumulation of plasticizers is essential to assessing their fate and potential toxicity in early life. In the present study, 311 infant hair samples and 271 paired meconium samples were collected at birth in Guangzhou, China, to characterize fetal exposure to legacy and emerging plasticizers and their metabolites. Results showed that most of the target plasticizers were detected in infant hair, with medians of 9.30, 27.6, and 0.145 ng/g for phthalate esters (PAEs), organic phosphate ester (OPEs), and alternative plasticizers (APs), and 1.44, 0.313, and 0.066 ng/g for the metabolites of PAEs, OPEs, and APs, respectively. Positive correlations between plasticizers and their corresponding primary metabolites, as well as correlations among the oxidative metabolites of bis(2-ethylhexyl) phthalate (DEHP) and 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH), were observed, indicating that infant hair retained the major phase-I metabolism of the target plasticizers. While no positive correlations were found in parent compounds or their primary metabolites between paired infant hair and meconium, significant positive correlations were observed among secondary oxidative metabolites of DEHP and DINCH in hair and meconium, suggesting that the primary metabolites in meconium come from hydrolysis of plasticizers in the fetus but most of the oxidative metabolites come from maternal-fetal transmission. The parent compound/metabolite ratios in infant hair showed a decreasing trend across pregnancy, suggesting in utero accumulation and deposition of plasticizers. To the best of our knowledge, this study is the first to report in utero exposure to both parent compounds and metabolites of plasticizers by using paired infant hair and meconium as noninvasive biomonitoring matrices and provides novel insights into the fetal biotransformation and accumulation of plasticizers across pregnancy.


Assuntos
Dietilexilftalato , Ácidos Ftálicos , Humanos , Gravidez , Recém-Nascido , Feminino , Plastificantes , Mecônio/metabolismo , Dietilexilftalato/metabolismo , Dietilexilftalato/toxicidade , Ácidos Ftálicos/metabolismo , Cabelo/metabolismo , Organofosfatos , Biotransformação , Ésteres/metabolismo , Exposição Ambiental/análise
13.
Lancet Digit Health ; 6(4): e261-e271, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38519154

RESUMO

BACKGROUND: Artificial intelligence (AI) models in real-world implementation are scarce. Our study aimed to develop a CT angiography (CTA)-based AI model for intracranial aneurysm detection, assess how it helps clinicians improve diagnostic performance, and validate its application in real-world clinical implementation. METHODS: We developed a deep-learning model using 16 546 head and neck CTA examination images from 14 517 patients at eight Chinese hospitals. Using an adapted, stepwise implementation and evaluation, 120 certified clinicians from 15 geographically different hospitals were recruited. Initially, the AI model was externally validated with images of 900 digital subtraction angiography-verified CTA cases (examinations) and compared with the performance of 24 clinicians who each viewed 300 of these cases (stage 1). Next, as a further external validation a multi-reader multi-case study enrolled 48 clinicians to individually review 298 digital subtraction angiography-verified CTA cases (stage 2). The clinicians reviewed each CTA examination twice (ie, with and without the AI model), separated by a 4-week washout period. Then, a randomised open-label comparison study enrolled 48 clinicians to assess the acceptance and performance of this AI model (stage 3). Finally, the model was prospectively deployed and validated in 1562 real-world clinical CTA cases. FINDINGS: The AI model in the internal dataset achieved a patient-level diagnostic sensitivity of 0·957 (95% CI 0·939-0·971) and a higher patient-level diagnostic sensitivity than clinicians (0·943 [0·921-0·961] vs 0·658 [0·644-0·672]; p<0·0001) in the external dataset. In the multi-reader multi-case study, the AI-assisted strategy improved clinicians' diagnostic performance both on a per-patient basis (the area under the receiver operating characteristic curves [AUCs]; 0·795 [0·761-0·830] without AI vs 0·878 [0·850-0·906] with AI; p<0·0001) and a per-aneurysm basis (the area under the weighted alternative free-response receiver operating characteristic curves; 0·765 [0·732-0·799] vs 0·865 [0·839-0·891]; p<0·0001). Reading time decreased with the aid of the AI model (87·5 s vs 82·7 s, p<0·0001). In the randomised open-label comparison study, clinicians in the AI-assisted group had a high acceptance of the AI model (92·6% adoption rate), and a higher AUC when compared with the control group (0·858 [95% CI 0·850-0·866] vs 0·789 [0·780-0·799]; p<0·0001). In the prospective study, the AI model had a 0·51% (8/1570) error rate due to poor-quality CTA images and recognition failure. The model had a high negative predictive value of 0·998 (0·994-1·000) and significantly improved the diagnostic performance of clinicians; AUC improved from 0·787 (95% CI 0·766-0·808) to 0·909 (0·894-0·923; p<0·0001) and patient-level sensitivity improved from 0·590 (0·511-0·666) to 0·825 (0·759-0·880; p<0·0001). INTERPRETATION: This AI model demonstrated strong clinical potential for intracranial aneurysm detection with improved clinician diagnostic performance, high acceptance, and practical implementation in real-world clinical cases. FUNDING: National Natural Science Foundation of China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.


Assuntos
Aprendizado Profundo , Aneurisma Intracraniano , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Angiografia por Tomografia Computadorizada , Inteligência Artificial , Estudos Prospectivos , Angiografia Cerebral/métodos
14.
NPJ Biofilms Microbiomes ; 10(1): 25, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38509085

RESUMO

Hyperuricemia (HUA) is a metabolic syndrome caused by abnormal purine metabolism. Although recent studies have noted a relationship between the gut microbiota and gout, whether the microbiota could ameliorate HUA-associated systemic purine metabolism remains unclear. In this study, we constructed a novel model of HUA in geese and investigated the mechanism by which Lactobacillus rhamnosus GG (LGG) could have beneficial effects on HUA. The administration of antibiotics and fecal microbiota transplantation (FMT) experiments were used in this HUA goose model. The effects of LGG and its metabolites on HUA were evaluated in vivo and in vitro. Heterogeneous expression and gene knockout of LGG revealed the mechanism of LGG. Multi-omics analysis revealed that the Lactobacillus genus is associated with changes in purine metabolism in HUA. This study showed that LGG and its metabolites could alleviate HUA through the gut-liver-kidney axis. Whole-genome analysis, heterogeneous expression, and gene knockout of LGG enzymes ABC-type multidrug transport system (ABCT), inosine-uridine nucleoside N-ribohydrolase (iunH), and xanthine permease (pbuX) demonstrated the function of nucleoside degradation in LGG. Multi-omics and a correlation analysis in HUA patients and this goose model revealed that a serum proline deficiency, as well as changes in Collinsella and Lactobacillus, may be associated with the occurrence of HUA. Our findings demonstrated the potential of a goose model of diet-induced HUA, and LGG and proline could be promising therapies for HUA.


Assuntos
Hiperuricemia , Lacticaseibacillus rhamnosus , Humanos , Hiperuricemia/terapia , Nucleosídeos , Lactobacillus , Prolina , Purinas
15.
Neural Netw ; 173: 106207, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38442651

RESUMO

Graph representation learning aims to effectively encode high-dimensional sparse graph-structured data into low-dimensional dense vectors, which is a fundamental task that has been widely studied in a range of fields, including machine learning and data mining. Classic graph embedding methods follow the basic idea that the embedding vectors of interconnected nodes in the graph can still maintain a relatively close distance, thereby preserving the structural information between the nodes in the graph. However, this is sub-optimal due to: (i) traditional methods have limited model capacity which limits the learning performance; (ii) existing techniques typically rely on unsupervised learning strategies and fail to couple with the latest learning paradigms; (iii) representation learning and downstream tasks are dependent on each other which should be jointly enhanced. With the remarkable success of deep learning, deep graph representation learning has shown great potential and advantages over shallow (traditional) methods, there exist a large number of deep graph representation learning techniques have been proposed in the past decade, especially graph neural networks. In this survey, we conduct a comprehensive survey on current deep graph representation learning algorithms by proposing a new taxonomy of existing state-of-the-art literature. Specifically, we systematically summarize the essential components of graph representation learning and categorize existing approaches by the ways of graph neural network architectures and the most recent advanced learning paradigms. Moreover, this survey also provides the practical and promising applications of deep graph representation learning. Last but not least, we state new perspectives and suggest challenging directions which deserve further investigations in the future.


Assuntos
Algoritmos , Mineração de Dados , Aprendizado de Máquina , Redes Neurais de Computação
16.
Front Public Health ; 12: 1275447, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38532972

RESUMO

Objective: To explore the effect of a video teach-back method on continuous family nursing care of stroke patients. Methods: Stroke patients hospitalized in our hospital between March 2020 and March 2023 who met the inclusion criteria were randomly divided into an intervention group (n = 45), who received routine health education plus video teach-back training of caregivers, and a control group (n = 45), who received routine health education only. The effects on nursing-related variables were compared between the two groups. Results: Total scores representing the caring ability of caregivers in the intervention group increased significantly over time relative to baseline and were higher than those of the control group. Scores representing the care burden of caregivers in the intervention group decreased significantly over time and were lower than those of the control group. Conclusion: The teach-back method combined with video education improves the nursing ability of family caregivers and can improve the self-care ability of stroke patients.


Assuntos
Acidente Vascular Cerebral , Humanos , Educação em Saúde/métodos , Pacientes , Escolaridade
17.
Heliyon ; 10(6): e27187, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38533077

RESUMO

Morphine is a widely used opioid for treatment of pain. The attendant problems including morphine tolerance and morphine dependence pose a major public health challenge. In recent years, there has been increasing interest in the gastrointestinal microbiota in many physiological and pathophysiological processes. The connectivity network between the gut microbiota and the brain is involved in multiple biological systems, and bidirectional communication between them is critical in gastrointestinal tract homeostasis, the central nervous system, and the microbial system. Many research have previously shown that morphine has a variety of effects on the gastrointestinal tract, but none have determined the function of intestinal microbiota in morphine tolerance. This study reviewed the mechanisms of morphine tolerance from the perspective of dysregulation of microbiota-gut-brain axis homeostasis, by summarizing the possible mechanisms originating from the gut that may affect morphine tolerance and the improvement of morphine tolerance through the gut microbiota.

18.
J Physiol Biochem ; 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38492180

RESUMO

Current study investigated the impact of maternal and postnatal overnutrition on phenotype of adipose, in relation to offspring thermogenesis and sex. Female C57BL/6 J mice were fed with CHOW or high fat diet (HFD) for 2 weeks before mating, throughout gestation and lactation. At weaning, pups were fed to 9 weeks old with CHOW or HFD, which resulted in four groups for each gender--male or female: CHOW-CHOW (CC), CHOW-HFD (CH), HFD-CHOW (HC), HFD-HFD (HH). Maternal and post-weaning HFD enhanced thermogenic factors such as Acox1, Dio2 and Cox8b in iBAT of male and female offspring, but increased SIRT1, PGC-1α and UCP1 only in female. However, Acox1, Dio2 and Cox8b mRNA expression and SIRT1, PGC-1α and UCP1 protein expression were only enhanced upon maternal and post-weaning HFD in sWAT and pWAT of female offspring. Increased metrnl expression in adipose were observed in sex- and depot-specific manner, while enhanced circulating metrnl level was only observed in male offspring undergoing maternal HFD. Palmitic acid changed metrnl expression during preadipocytes differentiation and siRNA-mediated knockdown of metrnl inhibited preadipocyte differentiation. Female offspring were more prone to resist adverse outcomes induced by maternal and post-weaning overnutrition, which probably related to metrnl expression and thermogenesis.

19.
Adv Sci (Weinh) ; : e2309348, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38498682

RESUMO

Tertiary lymphoid structure (TLS) can predict the prognosis and sensitivity of tumors to immune checkpoint inhibitors (ICIs) therapy, whether it can be noninvasively predicted by radiomics in hepatocellular carcinoma with liver transplantation (HCC-LT) has not been explored. In this study, it is found that intra-tumoral TLS abundance is significantly correlated with recurrence-free survival (RFS) and overall survival (OS). Tumor tissues with TLS are characterized by inflammatory signatures and high infiltration of antitumor immune cells, while those without TLS exhibit uncontrolled cell cycle progression and activated mTOR signaling by bulk and single-cell RNA-seq analyses. The regulators involved in mTOR signaling (RHEB and LAMTOR4) and S-phase (RFC2, PSMC2, and ORC5) are highly expressed in HCC with low TLS. In addition, the largest cohort of HCC patients is studied with available radiomics data, and a classifier is built to detect the presence of TLS in a non-invasive manner. The classifier demonstrates remarkable performance in predicting intra-tumoral TLS abundance in both training and test sets, achieving areas under receiver operating characteristic curve (AUCs) of 92.9% and 90.2% respectively. In summary, the absence of intra-tumoral TLS abundance is associated with mTOR signaling activation and uncontrolled cell cycle progression in tumor cells, indicating unfavorable prognosis in HCC-LT.

20.
Artigo em Inglês | MEDLINE | ID: mdl-38468152

RESUMO

BACKGROUND: Systemic inflammation and frailty have been implicated in osteoporosis (OP) and fracture risks; however, existing evidence remains limited and inconclusive. This study aimed to assess the associations of systemic inflammation and frailty phenotype with incident OP and fracture and to evaluate the mediating role of frailty phenotype. METHODS: The present study analysed data from the UK Biobank, a comprehensive and representative dataset encompassing over 500 000 individuals from the general population. Baseline peripheral blood cell counts were employed to calculate the systemic inflammation markers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII). Frailty phenotype was assessed using five criteria, defined as frail (≥3 items met), pre-frail (1-2 items met) and non-frail (0 items met). OP and fracture events were confirmed through participants' health-related records. Multivariable linear and Cox regression models were utilized, along with mediation analysis. RESULTS: Increased systemic inflammation was associated with increased risks of OP and fracture. The corresponding hazard ratios and 95% confidence intervals (CIs) for OP risk per standard deviation increase in the log-transformed NLR, PLR and SII were 1.113 (1.093-1.132), 1.098 (1.079-1.118) and 1.092 (1.073-1.111), and for fracture risk, they were 1.066 (1.051-1.082), 1.059 (1.044-1.075) and 1.073 (1.058-1.089), respectively. Compared with the non-frail individuals, the pre-frail and frail ones showed an elevated OP risk by 21.2% (95% CI: 16.5-26.2%) and 111.0% (95% CI: 98.1-124.8%), respectively, and an elevated fracture risk by 6.1% (95% CI: 2.8-9.5%) and 38.2% (95% CI: 30.7-46.2%), respectively. The systemic inflammation level demonstrated a positive association with frailty, with ß (95% CI) of 0.034 (0.031-0.037), 0.026 (0.023-0.029) and 0.008 (0.005-0.011) in response to per standard deviation increment in log-transformed SII, NLR and PLR, respectively. The frailty phenotype mediated the association between systemic inflammation and OP/fracture risk. Subgroup and sensitivity analyses confirmed the robustness of these findings. CONCLUSIONS: Systemic inflammation and frailty phenotype are independently linked to increased risks of OP and fracture. The frailty phenotype partially mediates the association between systemic inflammation and osteoporotic traits. These results highlight the significance of interventions targeting systemic inflammation and frailty in OP and fracture prevention and management.

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