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1.
Mol Carcinog ; 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38477642

RESUMO

Acute myeloid leukemia (AML) is one of the most prevalent types of leukemia and is challenging to cure for most patients. Basic Leucine Zipper ATF-Like Transcription Factor (BATF) has been reported to participate in the development and progression of numerous tumors. However, its role in AML is largely unknown. In this study, the expression and prognostic value of BATF were examined in AML. Our results demonstrated that BATF expression was upregulated in AML patients, which was significantly correlated with poor clinical characteristics and survival. Afterward, functional experiments were performed after knocking down or overexpressing BATF by transfecting small interfering RNAs and overexpression plasmids into AML cells. Our findings revealed that BATF promoted the migratory and invasive abilities of AML cells in vitro and in vivo. Moreover, the target genes of BATF were searched from databases to explore the binding of BATF to the target gene using ChIP and luciferase assays. Notably, our observations validated that BATF is bound to the promoter region of TGF-ß1, which could transcriptionally enhance the expression of TGF-ß1 and activate the TGF-ß1/Smad/MMPs signaling pathway. In summary, our study established the aberrantly high expression of BATF and its pro-migratory function via the TGF-ß1-Smad2/3-MMP2/9 axis in AML, which provides novel insights into extramedullary infiltration of AML.

2.
Br J Haematol ; 2024 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-38369805

RESUMO

Chimeric antigen receptor T-cell (CAR-T) therapy targeting B-cell maturation antigen (BCMA) has shown profound efficacy and manageable toxicity in patients with relapsed/refractory multiple myeloma (RRMM). However, determining the best course of treatment for post-CAR-T therapy relapse remains a significant challenge. We conducted a retrospective analysis of patients from the phase I LEGEND-2 study (NCT03090659) enrolled at the Xi'an site, analysing the first salvage line of therapy and outcomes in patients with RRMM who progressed after receiving LCAR-B38M CAR-T therapy. Of 45 eligible patients, 34 (76%) had progressive disease (PD). Overall response rate (ORR) to salvage treatment was 50.0%. Median progression-free survival (PFS) after starting salvage treatment was 16.3 months. Median PFS of patients receiving proteasome inhibitor (PI)-based combination therapy was longer (28.2 months) than that of patients receiving a second BCMA CAR-T (including LCAR-B38M; 3.9 months, p = 0.0022) or chemotherapy (1.67 months, p = 0.0001). All patients with extramedullary disease at baseline (n = 11) progressed after CAR-T therapy; ORR to salvage therapy was 25.0% and median PFS was 9.7 months. In conclusion, salvage therapy in patients with PD after receiving LCAR-B38M CAR-T cells produced moderate efficacy, with better outcomes for PI-based salvage regimens.

3.
Sci Adv ; 10(2): eadi7606, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38198557

RESUMO

Nuclear import of the hepatitis B virus (HBV) nucleocapsid is essential for replication that occurs in the nucleus. The ~360-angstrom HBV capsid translocates to the nuclear pore complex (NPC) as an intact particle, hijacking human importins in a reaction stimulated by host kinases. This paper describes the mechanisms of HBV capsid recognition by importins. We found that importin α1 binds a nuclear localization signal (NLS) at the far end of the HBV coat protein Cp183 carboxyl-terminal domain (CTD). This NLS is exposed to the capsid surface through a pore at the icosahedral quasi-sixfold vertex. Phosphorylation at serine-155, serine-162, and serine-170 promotes CTD compaction but does not affect the affinity for importin α1. The binding of 30 importin α1/ß1 augments HBV capsid diameter to ~620 angstroms, close to the maximum size trafficable through the NPC. We propose that phosphorylation favors CTD externalization and prompts its compaction at the capsid surface, exposing the NLS to importins.


Assuntos
Vírus da Hepatite B , Nucleocapsídeo , Humanos , Transporte Ativo do Núcleo Celular , Carioferinas , Proteínas do Capsídeo , Fatores Imunológicos , Serina
4.
Neurol Sci ; 45(4): 1419-1428, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38102519

RESUMO

In recent years, the stroke incidence has been increasing year by year, and the related sequelae after stroke, such as cognitive impairment, motor dysfunction, and post-stroke depression, seriously affect the patient's rehabilitation and daily activities. Repetitive transcranial magnetic stimulation (rTMS), as a safe, non-invasive, and effective new rehabilitation method, has been widely recognized in clinical practice. This article reviews the application and research progress of rTMS in treating different functional impairments (cognitive impairment, motor dysfunction, unilateral spatial neglect, depression) after stroke in recent years, and preliminary summarized the possible mechanisms. It has been found that the key parameters that determine the effectiveness of rTMS in improving post-stroke functional impairments include pulse number, stimulated brain areas, stimulation intensity and frequency, as well as duration. Generally, high-frequency stimulation is used to excite the ipsilateral cerebral cortex, while low-frequency stimulation is used to inhibit the contralateral cerebral cortex, thus achieving a balance of excitability between the two hemispheres. However, the specific mechanisms and the optimal stimulation mode for different functional impairments have not yet reached a consistent conclusion, and more research is needed to explore and clarify the best way to use rTMS. Furthermore, we will identify the issues and challenges in the current research, explore possible mechanisms to deepen understanding of rTMS, propose future research directions, and offer insightful insights for better clinical applications.


Assuntos
Agnosia , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Estimulação Magnética Transcraniana , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia , Encéfalo , Córtex Cerebral
5.
J Mol Biol ; 435(24): 168365, 2023 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-37952769

RESUMO

Bacteriophage P22 is a prototypical member of the Podoviridae superfamily. Since its discovery in 1952, P22 has become a paradigm for phage transduction and a model for icosahedral viral capsid assembly. Here, we describe the complete architecture of the P22 tail apparatus (gp1, gp4, gp10, gp9, and gp26) and the potential location and organization of P22 ejection proteins (gp7, gp20, and gp16), determined using cryo-EM localized reconstruction, genetic knockouts, and biochemical analysis. We found that the tail apparatus exists in two equivalent conformations, rotated by ∼6° relative to the capsid. Portal protomers make unique contacts with coat subunits in both conformations, explaining the 12:5 symmetry mismatch. The tail assembles around the hexameric tail hub (gp10), which folds into an interrupted ß-propeller characterized by an apical insertion domain. The tail hub connects proximally to the dodecameric portal protein and head-to-tail adapter (gp4), distally to the trimeric tail needle (gp26), and laterally to six trimeric tailspikes (gp9) that attach asymmetrically to gp10 insertion domain. Cryo-EM analysis of P22 mutants lacking the ejection proteins gp7 or gp20 and biochemical analysis of purified recombinant proteins suggest that gp7 and gp20 form a molecular complex associated with the tail apparatus via the portal protein barrel. We identified a putative signal transduction pathway from the tailspike to the tail needle, mediated by three flexible loops in the tail hub, that explains how lipopolysaccharide (LPS) is sufficient to trigger the ejection of the P22 DNA in vitro.


Assuntos
Bacteriófago P22 , Salmonella typhimurium , Bacteriófago P22/genética , Bacteriófago P22/química , Bacteriófago P22/metabolismo , Proteínas do Capsídeo/química , Salmonella typhimurium/virologia , Proteínas da Cauda Viral/genética
6.
Front Physiol ; 14: 1197224, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37398904

RESUMO

Objective: The purpose of this study was to employ metabolomics for the analysis of urine metabolites in swimmers, with the aim of establishing models for assessing their athletic status and competitive potential. Furthermore, the study sought to compare the identification efficacy of multi-component (urine and blood) model versus single-component (urine or blood) models, in order to determine the optimal approach for evaluating training and competitive status. Methods: A total of 187 Chinese professional swimmers, comprising 103 elite and 84 sub-elite level athletes, were selected as subjects for this study. Urine samples were obtained from each participant and subjected to nuclear magnetic resonance (NMR) metabolomics analysis. Significant urine metabolites were screened through multivariable logistic regression analysis, and an identification model was established. Based on the previously established model of blood metabolites, this study compared the discriminative and predictive performance of three models: either urine or blood metabolites model and urine + blood metabolites model. Results: Among 39 urine metabolites, 10 were found to be significantly associated with the athletic status of swimmers (p < 0.05). Of these, levels of 2-KC, cis-aconitate, formate, and LAC were higher in elite swimmers compared to sub-elite athletes, while levels of 3-HIV, creatinine, 3-HIB, hippurate, pseudouridine, and trigonelline were lower in elite swimmers. Notably, 2-KC and 3-HIB exhibited the most substantial differences. An identification model was developed to estimate physical performance and athletic level of swimmers while adjusting for different covariates and including 2-KC and 3-HIB. The urine metabolites model showed an area under the curve (AUC) of 0.852 (95% CI: 0.793-0.912) for discrimination. Among the three identification models tested, the combination of urine and blood metabolites showed the highest performance than either urine or blood metabolites, with an AUC of 0.925 (95% CI: 0.888-0.963). Conclusion: The two urine metabolites, 2-KC and 3-HIV, can serve as significant urine metabolic markers to establish a discrimination model for identifying the athletic status and competitive potential of Chinese elite swimmers. Combining two screened urine metabolites with four metabolites reported exhibiting significant differences in blood resulted in improved predictive performance compared to using urine metabolites alone. These findings indicate that combining blood and urine metabolites has a greater potential for identifying and predicting the athletic status and competitive potential of Chinese professional swimmers.

7.
Nat Commun ; 14(1): 4052, 2023 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-37422479

RESUMO

E217 is a Pseudomonas phage used in an experimental cocktail to eradicate cystic fibrosis-associated Pseudomonas aeruginosa. Here, we describe the structure of the whole E217 virion before and after DNA ejection at 3.1 Å and 4.5 Å resolution, respectively, determined using cryogenic electron microscopy (cryo-EM). We identify and build de novo structures for 19 unique E217 gene products, resolve the tail genome-ejection machine in both extended and contracted states, and decipher the complete architecture of the baseplate formed by 66 polypeptide chains. We also determine that E217 recognizes the host O-antigen as a receptor, and we resolve the N-terminal portion of the O-antigen-binding tail fiber. We propose that E217 design principles presented in this paper are conserved across PB1-like Myoviridae phages of the Pbunavirus genus that encode a ~1.4 MDa baseplate, dramatically smaller than the coliphage T4.


Assuntos
Fagos de Pseudomonas , Fagos de Pseudomonas/genética , Microscopia Crioeletrônica , Antígenos O , Microscopia Eletrônica , Myoviridae , Bacteriófago T4/química
8.
Front Physiol ; 14: 1096423, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37469561

RESUMO

Objective: The aim of this study was to compare the variances in-game loads exhibited by Chinese women's 3 × 3 basketball team across different stages of the preparation cycle for the Tokyo Olympic Games, and to summarize the fundamental regulations governing Chinese women's 3 × 3 basketball training and games, in order to establish a theoretical research foundation for the team's new preparation cycle. Methods: This study measured load-related data during the preparation and main competition periods of the 2019-2021 Tokyo Olympics, from April to August 2019 and from April to June 2021. The aim was to compare the changes and differences in a load of competition during different stages and to explore patterns of load changes during the preparation period. This study used wearable devices authorized by FIFA and NBA, along with the Catapult GPS performance monitoring system from Australia (Catapult&Polar Team) as instruments for collecting sports load data. The OptimEye S5 device was worn around the athlete's neck to collect data prior to the game, while the Open Field™ system was utilized for data editing and report generation post-game. Results: Compared to the primary competition load during the 2019 preparation period, the 2021 preparation period exhibited significant increases and decreases (p < 0.05) in competition load, high-intensity load, the number of explosive moves, the number of high-intensity acceleration, several changes to the left and right, and the number of explosive jumps. During the 2021 preparation period, the mean heart rate, mean heart rate percentage, and mean speed of the race demonstrated significant decreases in comparison to the race during the 2019 preparation period (p < 0.05). Throughout the training period spanning from 2019 to 2021, no significant differences were observed in running distance and maximum speed (p > 0.05). Conclusion: The findings of this study reveal that the national training team has fostered positive adaptive changes in athletes, resulting in a significant enhancement in both load and sports performance science data during competition from 2019 to 2021.

9.
Anal Chem ; 95(25): 9462-9470, 2023 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-37243709

RESUMO

Lack of controls and understanding in nucleation, which proceeds crystal growth and other phase transitions, has been a bottleneck challenge in chemistry, materials, biology, and other fields. The exemplary needs for better methods for biomacromolecule crystallization include (1) synthesizing crystals for high-resolution structure determinations in fundamental research and (2) tuning the crystal habit and thus the corresponding properties in materials and pharmaceutical applications. Herein, a deterministic method is established capable of sustaining the nucleation and growth of a single crystal using the protein lysozyme as a prototype. The supersaturation is localized at the interface between a sample and a precipitant solution, spatially confined by the tip of a single nanopipette. The exchange of matter between the two solutions determines the supersaturation, which is controlled by electrokinetic ion transport driven by an external potential waveform. Nucleation and subsequent crystal growth disrupt the ionic current limited by the nanotip and are detected. The nucleation and growth of individual single crystals are measured in real time. Electroanalytical and optical signatures are elucidated as feedbacks with which active controls in crystal quality and method consistency are achieved: five out of five crystals diffract at a true atomic resolution of up to 1.2 Å. As controls, those synthesized under less optimized conditions diffract poorly. The crystal habits during the growth process are tuned successfully by adjusting the flux. The universal mechanism of nano-transport kinetics, together with the correlations of the diffraction quality and crystal habit with the crystallization control parameters, lay the foundation for the generalization to other materials systems.


Assuntos
Proteínas , Proteínas/química , Cristalização/métodos , Transição de Fase , Cinética
10.
Biol Reprod ; 108(6): 871-886, 2023 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-36961504

RESUMO

The regulation of mammalian early-embryonic development is a complex, coordinated process that involves widespread transcriptomic and epigenetic remodeling. The main cause of developmental failure in preimplantation embryos after in vitro fertilization is the irreversible arrested-at-cleavage stage. To deepen our understanding of this embryonic block, we profiled a single-cell multi-omics map of copy number variations (CNVs), the transcriptome, the DNA methylome, and the chromatin state of bovine eight-cell embryos with a two-cell fate that either arrested or developed into blastocysts. To do this, we sequenced a biopsied blastomere and tracked the developmental potential of the remaining cells. Aneuploid embryos inferred by CNVs from DNA- and RNA-library data tended to lose their developmental potency. Analysis of distinct genomic regions of DNA methylation and chromatin accessibility revealed that enrichment of gene function and signaling pathways, such as the MAPK signaling pathway, was altered in arrested euploid eight-cell embryos compared with blastocyst-developed euploid eight-cell embryos. Moreover, the RNA expression and chromatin accessibility of embryonic genome activation-associated genes were lower in arrested euploid embryos than in blastocyst-developed embryos. Taken together, our results indicate that the developmental block of eight-cell embryos can be caused by multiple molecular layers, including CNVs, abnormality of DNA methylation and chromatin accessibility, and insufficient expression of embryonic genome activation-associated genes. Our integrated and comprehensive data set provides a valuable resource to further dissect the exact mechanisms underlying the arrest of bovine eight-cell embryos in vitro.


Assuntos
Variações do Número de Cópias de DNA , Multiômica , Gravidez , Feminino , Bovinos , Animais , Blastocisto/metabolismo , Desenvolvimento Embrionário/genética , Fertilização In Vitro/veterinária , Cromatina/metabolismo , RNA/metabolismo , Mamíferos/genética
11.
Orthop Clin North Am ; 54(2): 169-192, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36894290

RESUMO

Artificial intelligence (AI) is used in the clinic to improve patient care. While the successes illustrate AI's impact, few studies have led to improved clinical outcomes. In this review, we focus on how AI models implemented in nonorthopedic fields of corrosion science may apply to the study of orthopedic alloys. We first define and introduce fundamental AI concepts and models, as well as physiologically relevant corrosion damage modes. We then systematically review the corrosion/AI literature. Finally, we identify several AI models that may be implemented to study fretting, crevice, and pitting corrosion of titanium and cobalt chrome alloys.


Assuntos
Inteligência Artificial , Corpo Humano , Humanos , Corrosão , Ligas de Cromo , Titânio
12.
Clin Rehabil ; 37(7): 942-953, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36537108

RESUMO

OBJECTIVE: Parkinson's disease is one of the most common neurodegenerative diseases in the world, which seriously damages motor and balance ability. Dual-task training is discussed as an appropriate intervention. The aim of this review was to synthesize the existing research findings on the efficacy of dual-task training for people with Parkinson's disease. DATA RESOURCES: A systematic search on PubMed, CENTRAL, Embase, Web of Science, and PEDro, randomized-controlled trials (RCTs) of dual-task training for individuals with Parkinson's disease. METHODS: Articles published until 1 November 2022 were included. Our search identified 7 RCTs with a total of 406 subjects. Review Manager 5.4 software was used for bias evaluation and to process the results of the outcome measures collected from the investigations. RESULTS: Dual-task training was associated with significant improvement in most motor and balance outcomes including gait velocity (standard mean difference (SMD) = 0.62; 95% CI, 0.37-0.87; I2 = 31%; P = 0.21), cadence (SMD = 0.29; 95% CI, 0.05-0.53; I2 = 0%; P = 0.71), timed-up-and-go test (mean difference (MD) = -2.38; 95% CI, -3.93 to -0.84; I2 = 32%; P = 0.22) and mini-balance evaluation systems test (MD = 2.04; 95% CI, 1.05-3.03; I2 = 0%; P = 0.92). CONCLUSION: Evidence from meta-analyses suggests that dual-task training may improve motor and balance abilities in Parkinson's disease patients. Future research should focus on finding the most appropriate dual-task treatment model for patients with different degrees, in order to further improve the rehabilitation treatment of Parkinson's disease.


Assuntos
Doença de Parkinson , Humanos , Doença de Parkinson/reabilitação , Marcha , Modalidades de Fisioterapia , Atividades Cotidianas , Avaliação de Resultados em Cuidados de Saúde , Equilíbrio Postural
13.
Sci Adv ; 8(49): eadc9641, 2022 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-36475795

RESUMO

Sf6 is a bacterial virus that infects the human pathogen Shigella flexneri. Here, we describe the cryo-electron microscopy structure of the Sf6 tail machine before DNA ejection, which we determined at a 2.7-angstrom resolution. We built de novo structures of all tail components and resolved four symmetry-mismatched interfaces. Unexpectedly, we found that the tail exists in two conformations, rotated by ~6° with respect to the capsid. The two tail conformers are identical in structure but differ solely in how the portal and head-to-tail adaptor carboxyl termini bond with the capsid at the fivefold vertex, similar to a diamond held over a five-pronged ring in two nonidentical states. Thus, in the mature Sf6 tail, the portal structure does not morph locally to accommodate the symmetry mismatch but exists in two energetic minima rotated by a discrete angle. We propose that the design principles of the Sf6 tail are conserved across P22-like Podoviridae.

14.
Viruses ; 14(10)2022 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-36298770

RESUMO

The genome packaging motor of bacteriophages and herpesviruses is built by two terminase subunits, known as large (TerL) and small (TerS), both essential for viral genome packaging. TerL structure, composition, and assembly to an empty capsid, as well as the mechanisms of ATP-dependent DNA packaging, have been studied in depth, shedding light on the chemo-mechanical coupling between ATP hydrolysis and DNA translocation. Instead, significantly less is known about the small terminase subunit, TerS, which is dispensable or even inhibitory in vitro, but essential in vivo. By taking advantage of the recent revolution in cryo-electron microscopy (cryo-EM) and building upon a wealth of crystallographic structures of phage TerSs, in this review, we take an inventory of known TerSs studied to date. Our analysis suggests that TerS evolved and diversified into a flexible molecular framework that can conserve biological function with minimal sequence and quaternary structure conservation to fit different packaging strategies and environmental conditions.


Assuntos
Bacteriófagos , Montagem de Vírus , Montagem de Vírus/genética , Microscopia Crioeletrônica , Proteínas Virais/genética , DNA Viral/química , Empacotamento do DNA , Endodesoxirribonucleases/genética , Bacteriófagos/genética , Bacteriófagos/química , Trifosfato de Adenosina
15.
J Mol Neurosci ; 72(9): 1977-1989, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35861948

RESUMO

Mild cognitive impairment (MCI) is a pathological stage between normal cognitive aging and dementia. The blood-brain barrier (BBB) breakdown is emerging as an early biomarker of MCI. This study aimed to visually analyze the literatures related to MCI caused by BBB dysfunction in recent 20 years, systematically identify collaboration networks, track research trends, highlight current hot spots, and predict future frontiers in this field. The related literatures published from 2000 to 2021 were obtained from the Web of Science with the search term "mild cognitive impairment and (blood-brain barrier or neurovascular unit or neurovascular coupling)". VOSviewer software was used to present knowledge map, CiteSpace software was used to extract literature information and make tables, including the top most influential countries, authors, institutions, periodicals, keywords, and references. A total of 333 literatures were used for visual analysis. After 2013, the literatures in the field of BBB dysfunction-induced MCI showed an increased trend in terms of year of publication and quantity of material, with more than 40 publications published each year. USA, England, China, and Sweden cooperated closely. In terms of institutions, Harvard Med Sch ranked first in the number of papers published, followed by Mstricht Univ and Univ Washington. In terms of journals, three of the top five co-cited journals belonged to USA, the other two journals were Neurobiol Aging and J Alzheimers DIS, which were from England and Netherlands respectively. A total of 1752 authors were identified, with Abhay P Sagare the most published and Zlokovic BV the most cited. Keyword emergence detection analysis showed that inflammation, oxidative stress, and memory were new research hot spot in this field. Overall, the research on BBB dysfunction-induced MCI is booming. In the future, cooperation and communication between different countries and institutions should be strengthened.


Assuntos
Barreira Hematoencefálica , Disfunção Cognitiva , China , Humanos
16.
Front Nutr ; 9: 800901, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35571940

RESUMO

Research to date has provided novel insights into lactate's positive role in multiple brain functions and several brain diseases. Although notable controversies and discrepancies remain, the neurobiological role and the metabolic mechanisms of brain lactate have now been described. A theoretical framework on the relevance between lactate and brain function and brain diseases is presented. This review begins with the source and route of lactate formation in the brain and food; goes on to uncover the regulatory effect of lactate on brain function; and progresses to gathering the application and concentration variation of lactate in several brain diseases (diabetic encephalopathy, Alzheimer's disease, stroke, traumatic brain injury, and epilepsy) treatment. Finally, the dual role of lactate in the brain is discussed. This review highlights the biological effect of lactate, especially L-lactate, in brain function and disease studies and amplifies our understanding of past research.

17.
Front Physiol ; 13: 858869, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35600307

RESUMO

Objective: Metabolites in body fluids, such as lactate, glucose, and creatinine, have been measured by conventional methods to evaluate physical function and performance or athletic status. The objectives of the current study were to explore the novel metabolite biomarkers in professional swimmers with different competition levels using nuclear magnetic resonance (NMR) metabolomics, and try to establish a model to identify the athletic status or predict the competitive potential. Methods: Serum samples were collected from 103 elite and 84 sub-elite level Chinese professional swimmers, and were profiled by NMR analysis. Results: Out of the thirty-six serum metabolites profiled, ten were associated with the athletic status of swimmers (with p < 0.05). When compared with sub-elite swimmers, elite swimmers had higher levels of high-density lipoprotein (HDL), unsaturated fatty acid, lactic acid, and methanol. Elite swimmers had lower levels of isoleucine, 3-hydroxybutyric acid, acetoacetate, glutamine, glycine, and α-glucose. A model with four metabolites, including HDL, glutamine, methanol, and α-glucose, was established to predict athletic status by adjusting with different covariates. The area under the curve (AUC) of the best model was 0.904 (95% CI: 0.862-0.947), with a sensitivity and specificity of 75.5 and 90.2%, respectively. Conclusion: We have identified ten metabolite biomarkers with differentially expressed levels between elite and sub-elite swimmers, the differences could result from genetic or sports level between the two cohorts. A model with four metabolites has successfully differentiated professional swimmers with different competitive levels.

18.
J Mol Biol ; 434(9): 167537, 2022 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-35278476

RESUMO

Portal proteins are dodecameric assemblies that occupy a unique 5-fold vertex of the icosahedral capsid of tailed bacteriophages and herpesviruses. The portal vertex interrupts the icosahedral symmetry, and in vivo, its assembly and incorporation in procapsid are controlled by the scaffolding protein. Ectopically expressed portal oligomers are polymorphic in solution, and portal rings built by a different number of subunits have been documented in the literature. In this paper, we describe the cryo-EM structure of the portal protein from the Pseudomonas-phage PaP3, which we determined at 3.4 Å resolution. Structural analysis revealed a dodecamer with helical rather than rotational symmetry, which we hypothesize is kinetically trapped. The helical assembly was stabilized by local mispairing of portal subunits caused by the slippage of crown and barrel helices that move like a lever with respect to the portal body. Removing the C-terminal barrel promoted assembly of undecameric and dodecameric rings with quasi-rotational symmetry, suggesting that the barrel contributes to subunits mispairing. However, ΔC-portal rings were intrinsically asymmetric, with most particles having one open portal subunit interface. Together, these data expand the structural repertoire of viral portal proteins to Pseudomonas-phages and shed light on the unexpected plasticity of the portal protein quaternary structure.


Assuntos
Proteínas do Capsídeo , Capsídeo , Fagos de Pseudomonas , Capsídeo/química , Proteínas do Capsídeo/química , Microscopia Crioeletrônica , Conformação Proteica , Fagos de Pseudomonas/química , Montagem de Vírus
19.
J Transl Med ; 20(1): 60, 2022 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-35109880

RESUMO

BACKGROUND: High intensity interval training (HIIT) has been reported to exert better effects on cardiovascular fitness in obesity, but little known about the arterial stiffness (AS) in female university students with normal weight obesity (NWO). Thus, this study aimed to investigate the effects of HIIT on the body composition, heart rate (HR), blood pressure (BP), blood lipids metabolism as well as the novel parameters of propensity for AS (arterial velocity pulse index [AVI], arterial pressure volume index [API]) for female university students with NWO. METHODS: Forty female university students with NWO were randomly assigned to control group (n = 20) and HIIT group (3 bouts of 9­min intervals at 90% of the maximal heart rate [HRmax], interspersed by 1 min rest, 5 days a week, n = 20). Tests were performed before and after 4 weeks of training. Repeated measures ANOVA and simple effect test analysis were used to analyze dependent variable changes. RESULTS: After 4 weeks HIIT statistically significantly improved the body composition by decreasing the body mass index, body fat percent, total body fat mass (BFM), BFM of left arm, measured circumference of left arm, and obesity degree, and increasing the total body skeletal muscle mass, protein content, total body water, fat free mass, body cell mas, and InBody score. HIIT also statistically significantly decreased the HR and BP. As for the lipid profile, HIIT obviously ameliorated the blood lipids metabolism by decreasing the levels of total cholesterol (TC), triglyceride, low-density lipoprotein, and TC/HDL, and increasing the levels of high-density lipoprotein (HDL). In addition, the AVI and API were markedly decreased via HIIT intervention. CONCLUSIONS: HIIT produced significant and meaningful benefits for body composition, HR, BP, and blood lipids metabolism, and could decrease AS in female university students with NWO. This suggests that HIIT may effectively reduce the risk of arteriosclerosis and protect the cardiovascular function for female university students with NWO. Trial registration ChiCTR2100050711. Registered 3 September 2021. Retrospectively registered.


Assuntos
Treinamento Intervalado de Alta Intensidade , Rigidez Vascular , China , Feminino , Humanos , Obesidade/metabolismo , Obesidade/terapia , Projetos Piloto , Estudantes , Universidades
20.
J Mol Model ; 27(11): 310, 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34599669

RESUMO

The efficacy of borophene (BP) as catechol (CC) sensor was explored using density functional theory (DFT) method. All calculations were performed at B3LYP level of theory and 6-31 + G(d) basis set employing the dispersion correction term of Grimme to consider dispersion interactions. The CC molecule is adsorbed on top of BP horizontally with the adsorption energy (Eads) of about - 13.5 kcal·mol-1. The HOMO and LUMO levels of nanosheet destabilize by about 0.36 and 0.14 eV, respectively, going from bare BP to BP-CC complex. Therefore, the Eg value decreases by about 10.5% upon adsorption process, which is a reasonable energy gap change for detection of CC. The negligible difference between the work function values (Φ, defined as the minimum amount of the energy needed to remove an electron from a solid to a point in the vacuum immediately outside the solid surface) of BP and its complex with CC indicates that the BP sheet is not an appropriate Φ-type sensor (in these sensors, adsorption of a chemical changes the gate voltage and produces an electrical signal that leads to the detection of chemical agent) for CC detection. The electrical conductivity of BP becomes 72 times higher after CC adsorption. The time needed for CC desorption from BP sheet is 7.6 ns, based on conventional transition state theory, showing that BP benefits from a short recovery time. The effect of CC concentration was explored by adsorption of 2 and 3 CC molecules on top of BP nanosheet and the results showed that the sensor response does not change by increasing the CC concentration. Also, the effect of lateral dimensions of BP on the adsorption energy was explored and it was shown that Eads increases by enlargement of the nanosheet.

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