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1.
Biophys Rev (Melville) ; 5(1): 011304, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38559589

RESUMO

A key strength of echocardiography lies in its integration of comprehensive spatiotemporal cardiac imaging data in real-time, to aid frontline or bedside patient risk stratification and management. Nonetheless, its acquisition, processing, and interpretation are known to all be subject to heterogeneity from its reliance on manual and subjective human tracings, which challenges workflow and protocol standardization and final interpretation accuracy. In the era of advanced computational power, utilization of machine learning algorithms for big data analytics in echocardiography promises reduction in cost, cognitive errors, and intra- and inter-observer variability. Novel spatiotemporal deep learning (DL) models allow the integration of temporal arm information based on unlabeled pixel echocardiographic data for convolution of an adaptive semantic spatiotemporal calibration to construct personalized 4D heart meshes, assess global and regional cardiac function, detect early valve pathology, and differentiate uncommon cardiovascular disorders. Meanwhile, data visualization on spatiotemporal DL prediction models helps extract latent temporal imaging features to develop advanced imaging biomarkers in early disease stages and advance our understanding of pathophysiology to support the development of personalized prevention or treatment strategies. Since portable echocardiograms have been increasingly used as point-of-care imaging tools to aid rural care delivery, the application of these new spatiotemporal DL techniques show the potentials in streamlining echocardiographic acquisition, processing, and data analysis to improve workflow standardization and efficiencies, and provide risk stratification and decision supporting tools in real-time, to prompt the building of new imaging diagnostic networks to enhance rural healthcare engagement.

2.
Eur Heart J Digit Health ; 5(2): 134-143, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38505490

RESUMO

Aims: The spatiotemporal deep convolutional neural network (DCNN) helps reduce echocardiographic readers' erroneous 'judgement calls' on Takotsubo syndrome (TTS). The aim of this study was to improve the interpretability of the spatiotemporal DCNN to discover latent imaging features associated with causative TTS pathophysiology. Methods and results: We applied gradient-weighted class activation mapping analysis to visualize an established spatiotemporal DCNN based on the echocardiographic videos to differentiate TTS (150 patients) from anterior wall ST-segment elevation myocardial infarction (STEMI, 150 patients). Forty-eight human expert readers interpreted the same echocardiographic videos and prioritized the regions of interest on myocardium for the differentiation. Based on visualization results, we completed optical flow measurement, myocardial strain, and Doppler/tissue Doppler echocardiography studies to investigate regional myocardial temporal dynamics and diastology. While human readers' visualization predominantly focused on the apex of the heart in TTS patients, the DCNN temporal arm's saliency visualization was attentive on the base of the heart, particularly at the atrioventricular (AV) plane. Compared with STEMI patients, TTS patients consistently showed weaker peak longitudinal displacement (in pixels) in the basal inferoseptal (systolic: 2.15 ± 1.41 vs. 3.10 ± 1.66, P < 0.001; diastolic: 2.36 ± 1.71 vs. 2.97 ± 1.69, P = 0.004) and basal anterolateral (systolic: 2.70 ± 1.96 vs. 3.44 ± 2.13, P = 0.003; diastolic: 2.73 ± 1.70 vs. 3.45 ± 2.20, P = 0.002) segments, and worse longitudinal myocardial strain in the basal inferoseptal (-8.5 ± 3.8% vs. -9.9 ± 4.1%, P = 0.013) and basal anterolateral (-8.6 ± 4.2% vs. -10.4 ± 4.1%, P = 0.006) segments. Meanwhile, TTS patients showed worse diastolic mechanics than STEMI patients (E'/septal: 5.1 ± 1.2 cm/s vs. 6.3 ± 1.5 cm/s, P < 0.001; S'/septal: 5.8 ± 1.3 cm/s vs. 6.8 ± 1.4 cm/s, P < 0.001; E'/lateral: 6.0 ± 1.4 cm/s vs. 7.9 ± 1.6 cm/s, P < 0.001; S'/lateral: 6.3 ± 1.4 cm/s vs. 7.3 ± 1.5 cm/s, P < 0.001; E/E': 15.5 ± 5.6 vs. 12.5 ± 3.5, P < 0.001). Conclusion: The spatiotemporal DCNN saliency visualization helps identify the pattern of myocardial temporal dynamics and navigates the quantification of regional myocardial mechanics. Reduced AV plane displacement in TTS patients likely correlates with impaired diastolic mechanics.

4.
Animals (Basel) ; 14(5)2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38473118

RESUMO

Resource partitioning may allow species coexistence. Sand dunes in the typical steppe of Alxa Desert Inner Mongolia, China, consisting of desert, shrub, and grass habitats, provide an appropriate system for studies of spatial niche partitioning among small mammals. In this study, the spatial niche characteristics of four rodents, Orientallactaga sibirica, Meriones meridianus, Dipus sagitta, and Phodopus roborovskii, and their responses to environmental changes in the Alxa Desert were studied from 2017 to 2021. Using the capture-mark-recapture method, we tested if desert rodents with different biological characteristics and life history strategies under heterogeneous environmental conditions allocate resources in spatial niches to achieve sympatric coexistence. We investigated the influence of environmental factors on the spatial niche breadth of rodents using random forest and redundancy analyses. We observed that the spatial niche overlap between O. sibirica and other rodents is extremely low (overlap index ≤ 0.14). P. roborovskii had the smallest spatial niche breadth. Spatial niche overlap was observed in two distinct species pairs, M. meridianus and D. sagitta, and P. roborovskii and D. sagitta. The Pielou evenness index of rodent communities is closely related to the spatial distribution of rodents, and the concealment of habitats is a key factor affecting the spatial occupation of rodents.

5.
Adv Radiat Oncol ; 9(2): 101308, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38405319

RESUMO

Purpose: Spatially fractionated radiation therapy (SFRT) is increasingly used for bulky advanced tumors, but specifics of clinical SFRT practice remain elusive. This study aimed to determine practice patterns of GRID and Lattice radiation therapy (LRT)-based SFRT. Methods and Materials: A survey was designed to identify radiation oncologists' practice patterns of patient selection for SFRT, dosing/planning, dosimetric parameter use, SFRT platforms/techniques, combinations of SFRT with conventional external beam radiation therapy (cERT) and multimodality therapies, and physicists' technical implementation, delivery, and quality procedures. Data were summarized using descriptive statistics. Group comparisons were analyzed with permutation tests. Results: The majority of practicing radiation oncologists (United States, 100%; global, 72.7%) considered SFRT an accepted standard-of-care radiation therapy option for bulky/advanced tumors. Treatment of metastases/recurrences and nonmetastatic primary tumors, predominantly head and neck, lung cancer and sarcoma, was commonly practiced. In palliative SFRT, regimens of 15 to 18 Gy/1 fraction predominated (51.3%), and in curative-intent treatment of nonmetastatic tumors, 15 Gy/1 fraction (28.0%) and fractionated SFRT (24.0%) were most common. SFRT was combined with cERT commonly but not always in palliative (78.6%) and curative-intent (85.7%) treatment. SFRT-cERT time sequencing and cERT dose adjustments were variable. In curative-intent treatment, concurrent chemotherapy and immunotherapy were found acceptable by 54.5% and 28.6%, respectively. Use of SFRT dosimetric parameters was highly variable and differed between GRID and LRT. SFRT heterogeneity dosimetric parameters were more commonly used (P = .008) and more commonly thought to influence local control (peak dose, P = .008) in LRT than in GRID therapy. Conclusions: SFRT has already evolved as a clinical practice pattern for advanced/bulky tumors. Major treatment approaches are consistent and follow the literature, but SFRT-cERT combination/sequencing and clinical utilization of dosimetric parameters are variable. These areas may benefit from targeted education and standardization, and knowledge gaps may be filled by incorporating identified inconsistencies into future clinical research.

6.
PeerJ ; 12: e16811, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38406275

RESUMO

Dipus sagitta is a major rodent found in arid environments and desert areas. They feed on plant seeds, young branches and some small insects, and have hibernating habits. Peak Dipus sagitta numbers impact the construction of the plant community in the environment, but also have a human impact as these rodents carry a variety of parasitic fleas capable of spreading serious diseases to humans. Based on 216 present distribution records of Dipus sagitta and seven environmental variables, this article simulates the potential distribution of Dipus sagitta during the Last Glacial Maximum, the mid-Holocene, the present and the future (2070s, RCP4.5, RCP8.5). This study also analyzes the geographic changes of the population distribution and evaluates the importance of climate factors by integrating contribution rate, replacement importance value and the jackknife test using the MaxEnt model. In this study, we opted to assess the predictive capabilities of our model using the receiver operating characteristic (ROC) and partial receiver operating characteristic (pROC) metrics. The findings indicate that the AUC value exceeds 0.9 and the AUC ratio is greater than 1, indicating superior predictive performance by the model. The results showed that the main climatic factors affecting the distribution of the three-toed jerboa were precipitation in the coldest quarter, temperature seasonality (standard deviation), and mean annual temperature. Under the two warming scenarios of the mid-Holocene and the future, there were differences in the changes in the distribution area of the three-toed jerboa. During the mid-Holocene, the suitable distribution area of the three-toed jerboa expanded, with a 93.91% increase in the rate of change compared to the Last Glacial Maximum. The size of the three-toed jerboa's habitat decreases under both future climate scenarios. Compared to the current period, under the RCP4.5 emission scenario, the change rate is -2.96%, and under the RCP8.5 emission scenario, the change rate is -7.41%. This indicates a trend of contraction in the south and expansion in the north. It is important to assess changes in the geographic population of Dipus sagitta due to climate change to formulate population control strategies of these harmful rodents and to prevent and control the long-distance transmission of zoonotic diseases.


Assuntos
Mudança Climática , Ecossistema , Animais , Humanos , Temperatura , Roedores , Zoonoses/epidemiologia
7.
J Control Release ; 367: 791-805, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38341179

RESUMO

Epidural fibrosis (EF), associated with various biological factors, is still a major troublesome clinical problem after laminectomy. In the present study, we initially demonstrate that sensory nerves can attenuate fibrogenic progression in EF animal models via the secretion of calcitonin gene-related peptide (CGRP), suggesting a new potential therapeutic target. Further studies showed that CGRP could inhibit the reprograming activation of fibroblasts through PI3K/AKT signal pathway. We subsequently identified metformin (MET), the most widely prescribed medication for obesity-associated type 2 diabetes, as a potent stimulator of sensory neurons to release more CGRP via activating CREB signal way. We copolymerized MET with innovative polycaprolactone (PCL) nanofibers to develop a metformin-grafted PCL nanoscaffold (METG-PCLN), which could ensure stable long-term drug release and serve as favorable physical barriers. In vivo results demonstrated that local implantation of METG-PCLN could penetrate into dorsal root ganglion cells (DRGs) to promote the CGRP synthesis, thus continuously inhibit the fibroblast activation and EF progress for 8 weeks after laminectomy, significantly better than conventional drug loading method. In conclusion, this study reveals the unprecedented potential of sensory neurons to counteract EF through CGRP signaling and introduces a novel strategy employing METG-PCLN to obstruct EF by fine-tuning sensory nerve-regulated fibrogenesis.


Assuntos
Peptídeo Relacionado com Gene de Calcitonina , Diabetes Mellitus Tipo 2 , Poliésteres , Animais , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Fosfatidilinositol 3-Quinases , Fibrose , Fibroblastos/metabolismo
8.
J Affect Disord ; 353: 38-47, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38417715

RESUMO

PURPOSE: Previous studies have suggested a potential association between gut microbiota and neurological and psychiatric disorders. However, the causal relationship between gut microbiota and cognitive performance remains uncertain. METHODS: A two-sample Mendelian randomization (MR) study used SNPs linked to gut microbiota (n = 18,340) and cognitive performance (n = 257,841) from recent GWAS data. Inverse-variance weighted (IVW), MR Egger, weighted median, simple mode, and weighted mode were employed. Heterogeneity was assessed via Cochran's Q test for IVW. Results were shown with funnel plots. Outliers were detected through leave-one-out method. MR-PRESSO and MR-Egger intercept tests were conducted to address horizontal pleiotropy influence. LIMITATIONS: Limited to European populations, generic level, and potential confounding factors. RESULTS: IVW analysis revealed detrimental effects on cognitive perfmance associated with the presence of genus Blautia (P = 0.013, 0.966[0.940-0.993]), Catenibacterium (P = 0.035, 0.977[0.956-0.998]), Oxalobacter (P = 0.043, 0.979[0.960-0.999]). Roseburia (P < 0.001, 0.935[0.906-0.965]), in particular, remained strongly negatively associated with cognitive performance after Bonferroni correction. Conversely, families including Bacteroidaceae (P = 0.043, 1.040[1.001-1.081]), Rikenellaceae (P = 0.047, 1.026[1.000-1.053]), along with genera including Paraprevotella (P = 0.044, 1.020[1.001-1.039]), Ruminococcus torques group (P = 0.016, 1.062[1.011-1.115]), Bacteroides (P = 0.043, 1.040[1.001-1.081]), Dialister (P = 0.027, 1.039[1.004-1.074]), Paraprevotella (P = 0.044, 1.020[1.001-1.039]) and Ruminococcaceae UCG003 (P = 0.007, 1.040[1.011-1.070]) had a protective effect on cognitive performance. CONCLUSIONS: Our results suggest that interventions targeting specific gut microbiota may offer a promising avenue for improving cognitive function in diseased populations. The practical application of these findings has the potential to enhance cognitive performance, thereby improving overall quality of life.


Assuntos
Microbioma Gastrointestinal , Transtornos Mentais , Humanos , Microbioma Gastrointestinal/genética , Análise da Randomização Mendeliana , Qualidade de Vida , Cognição
9.
Gels ; 10(2)2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38391471

RESUMO

Cellulose aerogels have great prospects for noise reduction applications due to their sustainable value and superior 3D interconnected porous structures. The drying principle is a crucial factor in the preparation process for developing high-performance aerogels, particularly with respect to achieving high acoustic absorption properties. In this study, multifunctional cellulose nanocrystal (CNC) aerogels were conveniently prepared using two distinct freeze-drying principles: refrigerator conventional freezing (RCF) and liquid nitrogen unidirectional freezing (LnUF). The results indicate that the rapid RCF process resulted in a denser CNC aerogel structure with disordered larger pores, causing a stronger compressive performance (Young's modulus of 40 kPa). On the contrary, the LnUF process constructed ordered structures of CNC aerogels with a lower bulk density (0.03 g/cm3) and smaller apertures, resulting in better thermal stability, higher diffuse reflection across visible light, and especially increased acoustic absorption performance at low-mid frequencies (600-3000 Hz). Moreover, the dissipation mechanism of sound energy in the fabricated CNC aerogels is predicted by a designed porous media model. This work not only paves the way for optimizing the performance of aerogels through structure control, but also provides a new perspective for developing sustainable and efficient acoustic absorptive materials for a wide range of applications.

10.
Int J Nanomedicine ; 19: 1055-1076, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38322754

RESUMO

During the past decade, "membrane lipid therapy", which involves the regulation of the structure and function of tumor cell plasma membranes, has emerged as a new strategy for cancer treatment. Cholesterol is an important component of the tumor plasma membrane and serves an essential role in tumor initiation and progression. This review elucidates the role of cholesterol in tumorigenesis (including tumor cell proliferation, invasion/metastasis, drug resistance, and immunosuppressive microenvironment) and elaborates on the potential therapeutic targets for tumor treatment by regulating cholesterol. More meaningfully, this review provides an overview of cholesterol-integrated membrane lipid nanotherapeutics for cancer therapy through cholesterol regulation. These strategies include cholesterol biosynthesis interference, cholesterol uptake disruption, cholesterol metabolism regulation, cholesterol depletion, and cholesterol-based combination treatments. In summary, this review demonstrates the tumor nanotherapeutics based on cholesterol regulation, which will provide a reference for the further development of "membrane lipid therapy" for tumors.


Assuntos
Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Colesterol/metabolismo , Carcinogênese , Transformação Celular Neoplásica , Proliferação de Células , Microambiente Tumoral
11.
Ecol Evol ; 14(2): e10849, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38384828

RESUMO

Environmental stressors and disturbances can cause changes in an ecosystem's community structure, which can be reflected in its functional diversity. As grazing intensity increases, this causes changes in the environment that inevitably lead to changes in the community structure, which can especially affect rodents due to their sensitivity to the environment. The effects of grazing prohibition and overgrazing on the functional diversity of desert rodent communities in Alxa were studied in April, July, and October of 2018-2020. The trap-day method was used to study rodent communities in disturbed habitats. Five functional traits were selected and quantified: nutrition, life history, physiology, morphology, and activity rhythm. The results showed that: (1) The species composition of rodent communities in the Alxa Desert in spring and autumn was significantly correlated with the functional traits of the hibernation, reproductive cycle, and feeding habits. The species composition in the summer was only significantly correlated with the functional traits of reproductive cycle and diet. (2) The effects of overgrazing on the functional diversity of rodents in desert areas have significant temporal and spatial characteristics. (3) In spring and summer, overgrazing made the Functional Richness index of the rodent community lower than that of areas where grazing is prohibited, but the Functional Evenness index was higher than that of grazing-prohibition areas. In autumn, overgrazing increased the Functional Richness index of the rodent community and decreased the Functional Evenness index. The Functional Divergence index was higher in overgrazing areas than in grazing-prohibited ones. These results suggest that, in spring and summer, overgrazing reduced the ecological space utilization ability of rodent communities; however, the impact on the degree of utilization of community resources is more comprehensive. In autumn, overgrazing increases the ability of rodent communities to use ecological space but reduces resource efficiency. Overgrazing makes the niche differentiation of rodent communities higher, the degree of overlap lower, and the competition between species weaker. Therefore, overgrazing will affect the functional diversity of the community through the utilization of ecological space, resource utilization, interspecific competition, and niche.

12.
ACS Appl Mater Interfaces ; 16(7): 8895-8902, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38348831

RESUMO

Polymerized ionic liquid (PIL)-based gel polymer electrolytes (GPEs) are well known as highly safe and stable electrolytes but with low ambient ionic conductivity. Herein, we first designed and synthesized an IL monomer with a long and flexible side chain and then mixed it with LiTFSI and MEMPTFSI to construct a PIL-based GPE (denoted as GM-GPE). The special molecular structure of the monomer greatly improves the ionic transport through the PIL chain, and the introduction of MEMPTFSI plasticizer further improves the ionic conductivity, promoting a TFSI--anion-derived SEI formation to suppress Li dendrite growth and forming an electrostatic shielding effect of MEMP+ cations to promote the uniform deposition of Li+. Consequently, the as-prepared GM-GPE exhibits high ambient ionic conductivity (4.3 × 10-4 S cm-1, 30 °C), robust electrochemical stability, excellent thermal stability, nonflammability, and superior ability to inhibit Li dendrite growth. The resultant LiFePO4|GM-GPE|Li cell exhibits a high discharge capacity of 150 mA h g-1 at 0.2 C along with a good cycling stability and rate capability. This work brings about new guidance for the development of high-quality GPEs with high ionic conductivity, high stability, and safety for long cycling and dendrite-free lithium metal batteries.

13.
EJNMMI Res ; 14(1): 20, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38372908

RESUMO

BACKGROUND: In the present study, we aimed to investigate the role of baseline (B), interim (I) and end-of-treatment (Eot) 18F-FDG PET/CT in assessing the prognosis of diffuse large B cell lymphoma (DLBCL), so as to identify patients who need intensive treatment at an early stage. METHODS: A total of 127 DLBCL patients (62 men; 65 women; median age 62 years) were retrospectively analyzed in this study. Baseline (n = 127), interim (n = 127, after 3-4 cycles) and end-of-treatment (n = 53, after 6-8 cycles) PET/CT images were re-evaluated; semi-quantitative parameters such as maximum standardized uptake value of lesion-to-liver ratio (SUVmax(LLR)) and lesion-to-mediastinum ratio (SUVmax(LMR)), total metabolic tumor volume (TMTV) and total metabolic tumor volume (TLG) were recorded. ΔTLG1 was the change of interim relative to baseline TLG (I to B), ΔTLG2 (Eot to B). ΔSUVmax and ΔTMTV were the same algorithm. The visual Deauville 5-point scale (D-5PS) has been adopted as the major criterion for PET evaluation. Visual analysis (VA) and semi-quantitative parameters were assessed for the ability to predict progression-free survival (PFS) and overall survival (OS) by using Kaplan-Meier method, cox regression and logistic regression analysis. When visual and semi-quantitative analysis are combined, the result is only positive if both are positive. RESULTS: At a median follow-up of 34 months, the median PFS and OS were 20 and 32 months. The survival curve analysis showed that advanced stage and IPI score with poor prognosis, ΔSUVmax(LLR)1 < 89.2%, ΔTMTV1 < 91.8% and ΔTLG1 < 98.8%, ΔSUVmax(LLR)2 < 86.4% were significantly related to the shortening of PFS in patient (p < 0.05). ΔSUVmax(LLR)1 < 83.2% and ΔTLG1 < 97.6% were significantly correlated with the shortening of OS in patients (p < 0.05). Visual analysis showed that incomplete metabolic remission at I-PET and Eot-PET increased the risk of progress and death. In terms of predicting recurrence by I-PET, the combination of visual and semi-quantitative parameters showed higher positive predictive value (PPV) and specificity than a single index. CONCLUSION: Three to four cycles of R-CHOP treatment may be a time point for early prediction of early recurrence/refractory (R/R) patients and active preemptive treatment. Combined visual analysis with semi-quantitative parameters of 18F-FDG PET/CT at interim can improve prognostic accuracy and may allow for more precise screening of patients requiring early intensive therapy.

14.
Ann Clin Microbiol Antimicrob ; 23(1): 10, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38302964

RESUMO

OBJECTIVE: This study aims to identify the most effective diagnostic method for distinguishing pathogenic and non-pathogenic Gram-negative bacteria (GNB) in suspected pneumonia cases using metagenomic next-generation sequencing (mNGS) on bronchoalveolar lavage fluid (BALF) samples. METHODS: The effectiveness of mNGS was assessed on BALF samples collected from 583 patients, and the results were compared with those from microbiological culture and final clinical diagnosis. Three interpretational approaches were evaluated for diagnostic accuracy. RESULTS: mNGS outperformed culture significantly. Among the interpretational approaches, Clinical Interpretation (CI) demonstrated the best diagnostic performance with a sensitivity of 87.3%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 98.3%. CI's specificity was significantly higher than Simple Interpretation (SI) at 37.9%. Additionally, CI excluded some microorganisms identified as putative pathogens by SI, including Haemophilus parainfluenzae, Haemophilus parahaemolyticus, and Klebsiella aerogenes. CONCLUSION: Proper interpretation of mNGS data is crucial for accurately diagnosing respiratory infections caused by GNB. CI is recommended for this purpose.


Assuntos
Infecções Respiratórias , Humanos , Infecções Respiratórias/diagnóstico , Sequenciamento de Nucleotídeos em Larga Escala , Bactérias Gram-Negativas/genética , Metagenômica , Sensibilidade e Especificidade , Líquido da Lavagem Broncoalveolar
15.
mBio ; 15(2): e0315823, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38265238

RESUMO

The zoonotic Cryptosporidium parvum is a global contributor to infantile diarrheal diseases and opportunistic infections in immunocompromised or weakened individuals. Like other apicomplexans, it possesses several specialized secretory organelles, including micronemes, rhoptry, and dense granules. However, the understanding of cryptosporidial micronemal composition and secretory pathway remains limited. Here, we report a new micronemal protein in C. parvum, namely, thrombospondin (TSP)-repeat domain-containing protein-4 (CpTSP4), providing insights into these ambiguities. Immunostaining and enzyme-linked assays show that CpTSP4 is prestored in the micronemes of unexcysted sporozoites but secreted during sporozoite excystation, gliding, and invasion. In excysted sporozoites, CpTSP4 is also distributed on the two central microtubules unique to Cryptosporidium. The secretion and microtubular distribution could be completely blocked by the selective kinesin-5 inhibitors SB-743921 and SB-715992, resulting in the accumulation of CpTSP4 in micronemes. These support the kinesin-dependent microtubular trafficking of CpTSP4 for secretion. We also localize γ-tubulin, consistent with kinesin-dependent anterograde trafficking. Additionally, recombinant CpTSP4 displays nanomolar binding affinity to the host cell surface, for which heparin acts as one of the host ligands. A novel heparin-binding motif is identified and validated biochemically for its contribution to the adhesive property of CpTSP4 by peptide competition assays and site-directed mutagenesis. These findings shed light on the mechanisms of intracellular trafficking and secretion of a cryptosporidial micronemal protein and the interaction of a TSP-family protein with host cells.IMPORTANCECryptosporidium parvum is a globally distributed apicomplexan parasite infecting humans and/or animals. Like other apicomplexans, it possesses specialized secretory organelles in the zoites, in which micronemes discharge molecules to facilitate the movement and invasion of zoites. Although past and recent studies have identified several proteins in cryptosporidial micronemes, our understanding of the composition, secretory pathways, and domain-ligand interactions of micronemal proteins remains limited. This study identifies a new micronemal protein, namely, CpTSP4, that is discharged during excystation, gliding, and invasion of C. parvum sporozoites. The CpTSP4 secretion depends on the intracellular trafficking on the two Cryptosporidium-unique microtubes that could be blocked by kinesin-5/Eg5 inhibitors. Additionally, a novel heparin-binding motif is identified and biochemically validated, which contributes to the nanomolar binding affinity of CpTSP4 to host cells. These findings indicate that kinesin-dependent microtubular trafficking is critical to CpTSP4 secretion, and heparin/heparan sulfate is one of the ligands for this micronemal protein.


Assuntos
Criptosporidiose , Cryptosporidium parvum , Cryptosporidium , Humanos , Animais , Cryptosporidium parvum/metabolismo , Criptosporidiose/metabolismo , Cinesinas/metabolismo , Microtúbulos/metabolismo , Esporozoítos/metabolismo , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Heparina/metabolismo
16.
Sci Total Environ ; 916: 170253, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38253097

RESUMO

Root exudates are pivotal in plant stress responses, however, the impact of microplastics (MPs) on their release and characteristics remains poorly understood. This study delves into the effects of 0.05 % and 0.1 % (w/w) additions of polyethylene (PE) MPs on the growth and physiological properties of lettuce (Lactuca sativa L.) following 28 days of exposure. The release characteristics of root exudates were assessed using UV-vis and 3D-EEM. The results indicated that PE increased leaf number but did not significantly affect other agronomic traits or pigment contents. Notably, 0.05 % PE increased the total root length and surface area compared to the 0.1 % addition, while a non-significant trend towards decreased root activity was observed with PE MPs. PE MPs with 0.1 % addition notably reduced the DOC concentration in root exudates by 37.5 %, while 0.05 % PE had no impact on DOC and DON concentrations. PE addition increased the SUVA254, SUVA260, and SUVA280 values of root exudates, with the most pronounced effect seen in the 0.05 % PE treatment. This suggests an increase of aromaticity and hydrophobic components induced by PE addition. Fluorescence Regional Integration (FRI) analysis of 3D-EEM revealed that aromatic proteins (region I and II) were dominant in root exudates, with a slight increase in fulvic acid-like substances (region III) under 0.1 % PE addition. Moreover, prolonged PE exposure induced ROS damage in lettuce leaves, evidenced by a significant increase in content and production rate of O2·-. The decrease in CAT and POD activities may account for the lettuce's response to environmental stress, potentially surpassing its tolerance threshold or undergoing adaptive regulation. These findings underscore the potential risk of prolonged exposure to PE MPs on lettuce growth.


Assuntos
Microplásticos , Plásticos , Microplásticos/metabolismo , Plásticos/metabolismo , Polietileno/metabolismo , Alface , Hidroponia , Estresse Oxidativo
17.
Small ; : e2310603, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38279621

RESUMO

To improve the sluggish kinetics of the hydrogen evolution reaction (HER), a key component in water-splitting applications, there is an urgent desire to develop efficient, cost-effective, and stable electrocatalysts. Strain engineering is proving an efficient strategy for increasing the catalytic activity of electrocatalysts. This work presents the development of Ru-Au bimetallic aerogels by a simple one-step in situ reduction-gelation approach, which exhibits strain effects and electron transfer to create a remarkable HER activity and stability in an alkaline environment. The surface strain induced by the bimetallic segregated structure shifts the d-band center downward, enhancing catalysis by balancing the processes of water dissociation, OH* adsorption, and H* adsorption. Specifically, the optimized catalyst shows low overpotentials of only 24.1 mV at a current density of 10 mA cm-2 in alkaline electrolytes, surpassing commercial Pt/C. This study can contribute to the understanding of strain engineering in bimetallic electrocatalysts for HER at the atomic scale.

18.
Eur J Anaesthesiol ; 41(3): 226-233, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38230449

RESUMO

BACKGROUND: Sleep disturbances in the peri-operative period have been associated with adverse outcomes, including postoperative delirium (POD). However, research on sleep quality during the immediate postoperative period is limited. OBJECTIVES: This study aimed to investigate the association between sleep quality on the night of the operative day assessed using the Sleep Quality Numeric Rating Scale (SQ-NRS), and the incidence of POD in a large cohort of surgical patients. DESIGN: A prospective cohort study. SETTING: A tertiary hospital in China. PATIENTS: This study enrolled patients aged 65 years or older undergoing elective surgery under general anaesthesia. The participants were categorised into the sleep disturbance and no sleep disturbance groups according to their operative night SQ-NRS. MAIN OUTCOME MEASURES: The primary outcome was delirium incidence, whereas the secondary outcomes included acute kidney injury, stroke, pulmonary infection, cardiovascular complications and all-cause mortality within 1 year postoperatively. RESULTS: In total, 3072 patients were included in the analysis of this study. Among them, 791 (25.72%) experienced sleep disturbances on the night of operative day. Patients in the sleep disturbance group had a significantly higher risk of developing POD (adjusted OR 1.43, 95% CI 1.11 to 1.82, P  = 0.005). Subgroup analysis revealed that age 65-75 years; male sex; ASA III and IV; haemoglobin more than 12 g l -1 ; intra-operative hypotension; surgical duration more than 120 min; and education 9 years or less were significantly associated with POD. No interaction was observed between the subgroups. No significant differences were observed in the secondary outcomes, such as acute kidney injury, stroke, pulmonary infection, cardiovascular complications and all-cause mortality within 1 year postoperatively. CONCLUSIONS: The poor subjective sleep quality on the night of operative day was independently associated with increased POD risk, especially in certain subpopulations. Optimising peri-operative sleep may reduce POD. Further research should investigate potential mechanisms and causal relationships. TRIAL REGISTRY: chictr.org.cn: ChiCTR1900028545.


Assuntos
Injúria Renal Aguda , Infecções Cardiovasculares , Delírio , Delírio do Despertar , Acidente Vascular Cerebral , Idoso , Humanos , Masculino , Infecções Cardiovasculares/complicações , Delírio/diagnóstico , Delírio/epidemiologia , Delírio/etiologia , Delírio do Despertar/diagnóstico , Delírio do Despertar/epidemiologia , Delírio do Despertar/etiologia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Fatores de Risco , Qualidade do Sono , Feminino
19.
J Biomol Struct Dyn ; 42(1): 435-444, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37029713

RESUMO

Actin bundles are an important component of cellular cytoskeleton and participate in the movement of cells. The formation of actin bundles requires the participation of many actin binding proteins (ABPs). Fascin is a member of ABPs, which plays a key role in bundling filamentous actin (F-actin) to bundles. However, the detailed interactions between fascin and F-actin are unclear. In this study, we construct an atomic-level structure of fascin - F-actin complex based on a rather poor cryo-EM data with resolution of 20 nm. We first optimized the geometries of the complex by molecular dynamics (MD) simulation and analyzed the binding site and pose of fascin which bundles two F-actin chains. Next, binding free energy of fascin was calculated by MM/GBSA method. Finally, protein structure network analysis (PSNs) was performed to analyze the key residues for fascin binding. Our results show that residues of K22, E27, E29, K41, K43, R110, R149, K358, R408 and K471 on fascin are important for its bundling, which are in good agreement with the experimental data. On the other hand, the consistent results indicate that the atomic-level model of fascin - F-actin complex is reliable. In short, this model can be used to understand the detailed interactions between fascin and F-actin, and to develop novel potential drugs targeting fascin.Communicated by Ramaswamy H. Sarma.


Assuntos
Actinas , Simulação de Dinâmica Molecular , Actinas/química , Proteínas dos Microfilamentos/química , Proteínas dos Microfilamentos/metabolismo , Citoesqueleto de Actina/metabolismo
20.
Diabetes Res Clin Pract ; 207: 111032, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38049035

RESUMO

PURPOSE OF THE STUDY: Assessing the lower extremity arterial stenosis scores (LEASS) in patients with diabetic foot ulcer (DFU) is a challenging task that requires considerable time and efforts from physicians, and it may yield varying results. The presence of vascular wall calcification and other irrelevant tissue information surrounding the vessel can further compound the difficulties of this evaluation. Automatic detection of lower extremity arterial stenosis (LEAS) is expected to help doctors develop treatment plans for patients faster. METHODS: In this paper, we first reconstructed the 3D model of blood vessels by medical digital image processing and then utilized it as the training data for deep learning (DL) in conjunction with the non-calcified part of blood vessels in the original data. We proposed an improved model of vascular stenosis small target detection based on YOLOv5. We added Convolutional Block Attention Module (CBAM) in backbone, replaced Path Aggregation Network (PANET) with Bidirectional Feature Pyramid Network (BiFPN) and replaced C3 with GhostC3 in neck to improve the recognition of three types of stenosis targets (I: <50 %, II: 51 % - 99 %, III: completely occluded). Additionally, we utilized K-Means++ instead of K-Means for better algorithm convergence performance, and enhanced the Complete-IoU (CIoU) loss function to Alpha-Scylla-IoU (ASIoU) loss for faster reasoning and convergence. Lastly, we conducted comparisons between our approach and five other prominent models. RESULT: Our method had the best average ability to detect three types of stenosis with 85.40% mean Average Precision (mAP) and 74.60 Frames Per Second (FPS) and explored the possibility of applying DL to the detection of LEAS in diabetic foot. The code is available at github.com/wuchongxin/yolov5_LEAS.git.


Assuntos
Aprendizado Profundo , Diabetes Mellitus , Pé Diabético , Humanos , Constrição Patológica , Pé Diabético/diagnóstico , Algoritmos , Extremidade Inferior
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