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1.
Spine J ; 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38843961

RESUMO

BACKGROUND CONTEXT: Although the relationships between paraspinal muscles and lumbar degenerative disorders have been acknowledged, paraspinal muscle evaluation has not been incorporated into clinical therapies. PURPOSE: We aimed to establish a novel paraspinal muscle endurance and morphology (PMEM) score to better predict mechanical complications after lumbar fusion. STUDY DESIGN: Prospective cohort study. PATIENT SAMPLE: A total of 212 patients undergoing posterior lumbar interbody fusion with at least 1 year of follow-up were finally included. OUTCOME MEASURES: Mechanical complications including screw loosening, pseudarthrosis and other complications like cage subsidence, and patient-reported outcomes were evaluated at last follow-up. METHODS: The PMEM score comprised 1 functional muscular parameter (the performance time of the endurance test) and 2 imaging muscular parameters (relative functional cross-sectional area [rFCSA] of paraspinal extensor muscles [PEM] and psoas major [PS] on magnetic resonance imaging). The score was established based on a weighted scoring system created by rounding ß regression coefficients to the nearest integer in univariate logistic regression. The diagnostic performance of the PMEM score was determined by binary logistic regression model and receiver operating characteristic (ROC) curve with the area under the curve (AUC). Additionally, pairwise comparisons of ROC curves were conducted to compare the diagnostic performance of the PMEM score with conventional methods based on a single muscular parameter. Moreover, differences of mechanical complications and patient-reported outcomes among the PMEM categories were analyzed using Chi-square test with Bonferroni correction. RESULTS: The PMEM score, calculated by adding the scores for each parameter, ranges from 0 to 5 points. Patients with higher PMEM scores exhibited higher rates of mechanical complications (p<.001). Binary logistic regression revealed that the PMEM score was an independent factor of mechanical complications (p<.001, OR=2.002). Moreover, the AUC of the PMEM score (AUC=0.756) was significantly greater than those of the conventional methods including the endurance test (AUC=0.691, Z=2.036, p<.05), PEM rFCSA (AUC=.690, Z=2.016, p<.05) and PS rFCSA (AUC=0.640, Z=2.771, p<.01). In terms of the PMEM categories, a score of 0-1 was categorized as low-risk muscular state of mechanical complications; 2-3, as moderate; and 4-5, as high-risk state. Moving from the low-risk state to the high-risk state, there was a progressive increase in the rates of mechanical complications (13.8% vs. 32.1% vs. 72.7%; p<.001), and a decrease in the rates of clinically significant improvement of patient-reported outcomes (all p<.05). CONCLUSIONS: The PMEM score might comprehensively evaluate paraspinal muscle degeneration and exhibit greater ability in predicting mechanical complications than the conventional evaluations after lumbar fusion. Surgeons might develop individualized treatment strategy tailored to different muscle degeneration statuses reflected by the PMEM score for decreasing the risk of mechanical complications.

2.
Psychol Assess ; 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38900519

RESUMO

The Preschool Anxiety Scale (PAS) is a parent-report scale measuring young children's anxiety symptoms involving five specific anxiety symptoms (separation anxiety, physical injury fears, social phobia, obsessive-compulsive disorder, generalized anxiety) that load on a higher-order factor representing general anxiety shared by all specific anxiety symptom subtypes. Although the PAS has been widely used to assess anxiety symptoms in young children, few studies have tested its measurement invariance for group comparisons. Using data from a sample of 2,221 children and their parents/carers in the United Kingdom, this study investigated the measurement invariance of the higher-order model of the PAS across child age (4-6 years vs. 6-7 years), gender (girls vs. boys), parental anxiety (low vs. high level), and children's living circumstances (before vs. after the removal of COVID-19 restrictions). Our findings demonstrated the good factor structure, internal consistency, and convergent validity of the higher-order model of the PAS in all subgroups and supported its configural, metric, and scalar invariance across these subgroups. Therefore, the findings suggest that the PAS is a reliable and valid instrument for assessing specific anxiety symptoms and general anxiety among young children in the United Kingdom and that comparisons can be made between the subgroups under examination. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

3.
Bioinformatics ; 40(7)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38885365

RESUMO

MOTIVATION: ADP-ribosylation is a critical modification involved in regulating diverse cellular processes, including chromatin structure regulation, RNA transcription, and cell death. Bacterial ADP-ribosyltransferase toxins (bARTTs) serve as potent virulence factors that orchestrate the manipulation of host cell functions to facilitate bacterial pathogenesis. Despite their pivotal role, the bioinformatic identification of novel bARTTs poses a formidable challenge due to limited verified data and the inherent sequence diversity among bARTT members. RESULTS: We proposed a deep learning-based model, ARTNet, specifically engineered to predict bARTTs from bacterial genomes. Initially, we introduced an effective data augmentation method to address the issue of data scarcity in training ARTNet. Subsequently, we employed a data optimization strategy by utilizing ART-related domain subsequences instead of the primary full sequences, thereby significantly enhancing the performance of ARTNet. ARTNet achieved a Matthew's correlation coefficient (MCC) of 0.9351 and an F1-score (macro) of 0.9666 on repeated independent test datasets, outperforming three other deep learning models and six traditional machine learning models in terms of time efficiency and accuracy. Furthermore, we empirically demonstrated the ability of ARTNet to predict novel bARTTs across domain superfamilies without sequence similarity. We anticipate that ARTNet will greatly facilitate the screening and identification of novel bARTTs from bacterial genomes. AVAILABILITY AND IMPLEMENTATION: ARTNet is publicly accessible at http://www.mgc.ac.cn/ARTNet/. The source code of ARTNet is freely available at https://github.com/zhengdd0422/ARTNet/.


Assuntos
ADP Ribose Transferases , Biologia Computacional , Aprendizado Profundo , ADP Ribose Transferases/metabolismo , ADP Ribose Transferases/química , ADP Ribose Transferases/genética , Biologia Computacional/métodos , Toxinas Bacterianas/química , Toxinas Bacterianas/metabolismo , Toxinas Bacterianas/genética , Genoma Bacteriano , Bactérias/genética
4.
Comput Biol Med ; 178: 108693, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38850960

RESUMO

AIM: Kaempferitrin is an active component in Chenopodium ambrosioides, showing medicinal functions against liver cancer. This study aimed to identify the potential targets and pathways of kaempferitrin against liver cancer using network pharmacology and molecular docking, and verify the essential hub targets and pathway in mice model of SMMC-7721 cells xenografted tumors and SMMC-7721 cells. METHODS: Kaempferitrin therapeutical targets were obtained by searching SwissTargetPrediction, PharmMapper, STITCH, DrugBank, and TTD databases. Liver cancer specific genes were obtained by searching GeneCards, DrugBank, TTD, OMIM, and DisGeNET databases. PPI network of "kaempferitrin-targets-liver cancer" was constructed to screen the hub targets. GO, KEGG pathway and MCODE clustering analyses were performed to identify possible enrichment of genes with specific biological subjects. Molecular docking and molecular dynamics simulation were employed to determine the docking pose, potential and stability of kaempferitrin with hub targets. The potential anti-liver cancer mechanisms of kaempferitrin, as predicted by network pharmacology analyses, were verified by in vitro and in vivo experiments. RESULTS: 228 kaempferitrin targets and 2186 liver cancer specific targets were identified, of which 50 targets were overlapped. 8 hub targets were identified through network topology analysis, and only SIRT1 and TP53 had a potent binding activity with kaempferitrin as indicated by molecular docking and molecular dynamics simulation. MCODE clustering analysis revealed the most significant functional module of PPI network including SIRT1 and TP53 was mainly related to cell apoptosis. GO and KEGG enrichment analyses suggested that kaempferitrin exerted therapeutic effects on liver cancer possibly by promoting apoptosis via p21/Bcl-2/Caspase 3 signaling pathway, which were confirmed by in vivo and in vitro experiments, such as HE staining of tumor tissues, CCK-8, qRT-PCR and Western blot. CONCLUSION: This study provided not only insight into how kaempferitrin could act against liver cancer by identifying hub targets and their associated signaling pathways, but also experimental evidence for the clinical use of kaempferitrin in liver cancer treatment.

5.
Front Microbiol ; 15: 1373077, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38846566

RESUMO

Introduction: Folliculogenesis and oligo/anovulation are common pathophysiological characteristics in polycystic ovary syndrome (PCOS) patients, and it is also accompanied by gut microbiota dysbiosis. It is known that physical activity has beneficial effects on improving metabolism and promoting ovulation and menstrual cycle disorder in PCOS patients, and it can also modulate the gastrointestinal microbiota in human beings. However, the mechanism remains vague. Irisin, a novel myokine, plays a positive role in the mediating effects of physical activity. Methods: Mice were randomly divided into the control group, PCOS group and PCOS+irisin group. PCOS model was induced by dehydroepiandrosterone (DHEA) and high-fat diet (HFD). The PCOS+irisin group was given irisin 400µg/kg intraperitoneal injection every other day for 21 days. The serum sex hormones were measured by radioimmunoassay. Hematoxylin and Eosin (H&E) Staining and immunohistochemistry (IHC) were conducted on ovarian tissue. The feces microbiota and metabolomic characteristics were collected by 16S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC-MS). Results: In this study, we demonstrated that irisin supplementation alleviated reproductive endocrine disorders of PCOS mice, including estrous cycle disturbance, ovarian polycystic degeneration, and hyperandrogenemia. Irisin also improved the PCOS follicles dysplasia and ovulation disorders, while it had no significant effect on the quality of oocytes. Moreover, irisin could mitigate the decreased bacteria of Odoribacter and the increased bacteria of Eisenbergiella and Dubosiella in PCOS mice model. Moreover, irisin could alleviate the increased fecal metabolites: Methallenestril and PS (22:5(4Z,7Z,10Z,13Z,16Z)/ LTE4). Conclusion: These results suggest that irisin may alleviate the status of PCOS mice model by modulating androgen-induced gut microbiota dysbiosis and fecal metabolites. Hence, our study provided evidence that irisin may be considered as a promising strategy for the treatment of PCOS.

6.
Aquat Toxicol ; 273: 107010, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38917645

RESUMO

With the continuous development of the modern social economy, rubber has been widely used in our daily life. Tire and road wear particles (TRWPs) are generated by friction between tires and the road surface during the processes of driving, acceleration, and braking. TRWPs can be divided into three main components according to their source: tire tread, brake wear, and road wear. Due to urban runoff, TRWPs flow with rainwater into the aquatic environment and influence the surrounding aquatic organisms. As an emerging contaminant, TRWPs with the characteristics of small particles and strong toxicity have been given more attention recently. Here, we summarized the existing knowledge of the physical and chemical properties of TRWPs, the pathways of TRWPs into the water body, and the exposure routes of TRWPs. Furthermore, we introduced the biological effects of TRWPs involved in size, concentration, and shape, as well as key toxic compounds involved in heavy metals, polycyclic aromatic hydrocarbons (PAHs), N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD), and benzothiazole on aquatic organisms, and attempted to find the relevant factors influencing the toxic effects of TRWPs. In the context of existing policies that ignore pollution from TRWPs emissions in the aquatic environment, we also proposed measures to mitigate the impact of TRWPs in the future, as well as an outlook for TRWPs research.

7.
J Transl Med ; 22(1): 557, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38858729

RESUMO

BACKGROUND: Deciphering the role of plasma proteins in pancreatic cancer (PC) susceptibility can aid in identifying novel targets for diagnosis and treatment. METHODS: We examined the relationship between genetically determined levels of plasma proteins and PC through a systemic proteome-wide Mendelian randomization (MR) analysis utilizing cis-pQTLs from multiple centers. Rigorous sensitivity analyses, colocalization, reverse MR, replications with varying instrumental variable selections and additional datasets, as well as subsequent meta-analysis, were utilized to confirm the robustness of significant findings. The causative effect of corresponding protein-coding genes' expression and their expression pattern in single-cell types were then investigated. Enrichment analysis, between-protein interaction and causation, knock-out mice models, and mediation analysis with established PC risk factors were applied to indicate the pathogenetic pathways. These candidate targets were ultimately prioritized upon druggability and potential side effects predicted by a phenome-wide MR. RESULTS: Twenty-one PC-related circulating proteins were identified in the exploratory phase with no evidence for horizontal pleiotropy or reverse causation. Of these, 11 were confirmed in a meta-analysis integrating external validations. The causality at a transcription level was repeated for neutrophil elastase, hydroxyacylglutathione hydrolase, lipase member N, protein disulfide-isomerase A5, xyloside xylosyltransferase 1. The carbohydrate sulfotransferase 11 and histo-blood group ABO system transferase exhibited high-support genetic colocalization evidence and were found to affect PC carcinogenesis partially through modulating body mass index and type 2 diabetes, respectively. Approved drugs have been established for eight candidate targets, which could potentially be repurposed for PC therapies. The phenome-wide investigation revealed 12 proteins associated with 51 non-PC traits, and interference on protein disulfide-isomerase A5 and cystatin-D would increase the risk of other malignancies. CONCLUSIONS: By employing comprehensive methodologies, this study demonstrated a genetic predisposition linking 21 circulating proteins to PC risk. Our findings shed new light on the PC etiology and highlighted potential targets as priorities for future efforts in early diagnosis and therapeutic strategies of PC.


Assuntos
Proteínas Sanguíneas , Análise da Randomização Mendeliana , Neoplasias Pancreáticas , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/patologia , Humanos , Animais , Proteínas Sanguíneas/metabolismo , Terapia de Alvo Molecular , Locos de Características Quantitativas , Predisposição Genética para Doença , Proteômica , Regulação Neoplásica da Expressão Gênica , Genômica , Reprodutibilidade dos Testes , Multiômica
8.
Mol Biol Rep ; 51(1): 673, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38787479

RESUMO

BACKGROUND: T-type calcium channels, characterized as low-voltage activated (LVA) calcium channels, play crucial physiological roles across a wide range of tissues, including both the neuronal and nonneuronal systems. Using in situ hybridization and RNA interference (RNAi) techniques in vitro, we previously identified the tissue distribution and physiological function of the T-type calcium channel α1 subunit (DdCα1G) in the plant-parasitic nematode Ditylenchus destructor. METHODS AND RESULTS: To further characterize the functional role of DdCα1G, we employed a combination of immunohistochemistry and fungus-mediated RNAi and found that DdCα1G was clearly distributed in stylet-related tissue, oesophageal gland-related tissue, secretory-excretory duct-related tissue and male spicule-related tissue. Silencing DdCα1G led to impairments in the locomotion, feeding, reproductive ability and protein secretion of nematodes. To confirm the defects in behavior, we used phalloidin staining to examine muscle changes in DdCα1G-RNAi nematodes. Our observations demonstrated that defective behaviors are associated with related muscular atrophy. CONCLUSION: Our findings provide a deeper understanding of the physiological functions of T-type calcium channels in plant-parasitic nematodes. The T-type calcium channel can be considered a promising target for sustainable nematode management practices.


Assuntos
Actinas , Canais de Cálcio Tipo T , Interferência de RNA , Animais , Canais de Cálcio Tipo T/metabolismo , Canais de Cálcio Tipo T/genética , Actinas/metabolismo , Actinas/genética , Masculino , Fungos/genética , Inativação Gênica
9.
Research (Wash D C) ; 7: 0366, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38783913

RESUMO

Muscle strength (MS) is related to our neural and muscle systems, essential for clinical diagnosis and rehabilitation evaluation. Although emerging wearable technology seems promising for MS assessment, problems still exist, including inaccuracy, spatiotemporal differences, and analyzing methods. In this study, we propose a wearable device consisting of myoelectric and strain sensors, synchronously acquiring surface electromyography and mechanical signals at the same spot during muscle activities, and then employ a deep learning model based on temporal convolutional network (TCN) + Transformer (Tcnformer), achieving accurate grading and prediction of MS. Moreover, by combining with deep clustering, named Tcnformer deep cluster (TDC), we further obtain a 25-level classification for MS assessment, refining the conventional 5 levels. Quantification and validation showcase a patient's postoperative recovery from level 3.2 to level 3.6 in the first few days after surgery. We anticipate that this system will importantly advance precise MS assessment, potentially improving relevant clinical diagnosis and rehabilitation outcomes.

10.
BMC Musculoskelet Disord ; 25(1): 418, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38807200

RESUMO

BACKGROUND: It was reported the paraspinal muscle played an important role in spinal stability. The preoperative paraspinal muscle was related to S1 screw loosening. But the relationship between preoperative and postoperative change of psoas major muscle (PS) and S1 pedicle screw loosening in degenerative lumbar spinal stenosis (DLSS) patients has not been reported. This study investigated the effects of preoperative and follow-up variations in the psoas major muscle (PS) on the first sacral vertebra (S1) screw loosening in patients with DLSS. METHODS: 212 patients with DLSS who underwent lumbar surgery were included. The patients were divided into the S1 screw loosening group and the S1 screw non-loosening group. Muscle parameters were measured preoperatively and at last follow-up magnetic resonance imaging. A logistic regression analysis was performed to investigate the risk factors for S1 screw loosening. RESULTS: The S1 screw loosening rate was 36.32% (77/212). The relative total cross-sectional areas and relative functional cross-sectional areas (rfCSAs) of the PS at L2-S1 were significantly higher after surgery. The increased rfCSA values of the PS at L3-S1 in the S1 screw non-loosening group were significantly higher than those in the S1 screw loosening group. The regression analysis showed male, lower CT value of L1 and longer segment fusion were independent risk factors for S1 screw loosening, and postoperative hypertrophy of the PS was a protective factor for S1 screw loosening. CONCLUSIONS: Compared to the preoperative muscle, the PS size increased and fatty infiltration decreased after surgery from L2-3 to L5-S1 in patients with DLSS after short-segment lumbar fusion surgery. Postoperative hypertrophy of the PS might be considered as a protective factor for S1 screw loosening. MRI morphometric parameters and postoperative selected exercise of PS for DLSS patients after posterior lumbar fusion surgery might contribute to improvement of surgical outcome.


Assuntos
Vértebras Lombares , Parafusos Pediculares , Músculos Psoas , Fusão Vertebral , Estenose Espinal , Humanos , Masculino , Estenose Espinal/cirurgia , Estenose Espinal/diagnóstico por imagem , Feminino , Vértebras Lombares/cirurgia , Vértebras Lombares/diagnóstico por imagem , Idoso , Músculos Psoas/diagnóstico por imagem , Pessoa de Meia-Idade , Seguimentos , Fusão Vertebral/instrumentação , Fusão Vertebral/efeitos adversos , Imageamento por Ressonância Magnética , Sacro/diagnóstico por imagem , Sacro/cirurgia , Estudos Retrospectivos , Fatores de Risco , Idoso de 80 Anos ou mais , Período Pré-Operatório
11.
Int J Biol Macromol ; 270(Pt 1): 132362, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38750864

RESUMO

The prophylactic and adjunctive impacts of compound prebiotics (CP), comprising galacto-oligosaccharides, fructo-oligosaccharides, and isomalto-oligosaccharides, on colitis remain unclear. This study aimed to elucidate the effects of CP on dextran sodium sulfate (DSS)-induced colitis via modulation of the gut microbiota. Mice received prophylactic CP (PCP) for three weeks and DSS in the second week. In the third week, therapeutic CP, mesalazine, and a combination of CP and mesalazine (CPM) were administered to mice with DSS-induced colitis. The administration of PCP and CPM was found to ameliorate colitis, as evidenced by increases in body weight and colon length, elevation of the anti-inflammatory cytokine IL-10, and reductions in the disease activity index, histological scores, and levels of pro-inflammatory cytokines in mice with DSS-induced colitis on days 14 or 21. Furthermore, an increase in the relative abundance of probiotics (Ligilactobacillus, Bifidobacterium, and Limosilactobacillus), alpha diversity indices, short-chain fatty acids (SCFA) contents, and microbial network complexity was observed following PCP or CPM treatment. Correlation analysis revealed positive associations between these probiotics and both SCFA and IL-10, and negative associations with pro-inflammatory cytokines. This study highlighted the potential of CP as novel prophylactic and adjunctive treatments for alleviating DSS-induced intestinal inflammation and maintaining gut microbiota homeostasis.


Assuntos
Colite , Sulfato de Dextrana , Microbioma Gastrointestinal , Prebióticos , Animais , Prebióticos/administração & dosagem , Microbioma Gastrointestinal/efeitos dos fármacos , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/microbiologia , Sulfato de Dextrana/efeitos adversos , Camundongos , Masculino , Citocinas/metabolismo , Probióticos/farmacologia , Probióticos/uso terapêutico , Probióticos/administração & dosagem , Modelos Animais de Doenças , Interleucina-10/metabolismo , Ácidos Graxos Voláteis/metabolismo
12.
Nanomaterials (Basel) ; 14(9)2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38727333

RESUMO

We conducted a systematic investigation into the spectral and pulse characteristics of C and L-band Nonlinear Polarization Rotation (NPR) mode-locked fiber lasers effectively employing nonlinear polarization rotation technology. In our experimental setup, we achieved a stable mode-locked state at 1560.076 nm, exhibiting a 3 dB spectral bandwidth of 9.1 nm. As the pump power increased, we observed spectral shifts accompanied by shifts in the first Kelly sideband and the generation of new Kelly sidebands. In this paper, the phenomenon of spectral deviation is elucidated through the interplay of self-phase modulation, group velocity drift, and polarization-dependent isolator (PD-ISO) filter effect, with an analysis of the formation and deviation of Kelly sidebands. Notably, spectral shift persisted even when the pump power exceeded 200 mW. However, continuous pump power escalation led to soliton splitting, resulting in the formation of new soliton beams. Based on the simultaneous generation of spectral shift and pulse splitting, our study contributes to an enhanced understanding of soliton dynamics in ultrafast fiber lasers and lays a foundation for the application of high-repetition-frequency harmonic mode-locked lasers with tunable wavelengths.

13.
Small ; : e2311237, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38593376

RESUMO

Chemically converted graphene oxide laminate membranes, which exhibit stable interlayered nanochannels in aqueous environments, are receiving increasing attention owing to their potential for selective water and ion permeation. However, how the molecular properties of conversion agents influence the stabilization of nanochannels and how effectively nanochannels are stabilized have rarely been studied. In this study, mono-, di-, and tri-saccharide molecules of glucose (Glu), maltose (Glu2), and maltotriose (Glu3) are utilized, respectively, to chemically modify graphene oxide (GO). The aim is to create nanochannels with different levels of stability and investigate how these functional conversion agents affect the separation performance. The effects of the property differences between different conversion agents on nanochannel stabilization are demonstrated. An agent with efficient chemical reduction of GO and limited intercalation in the resulting nanochannel ensures satisfactory nanochannel stability during desalination. The stabilized membrane nanochannel exhibits a permeance of 0.69 L m-2 h-1 bar-1 and excellent Na2SO4 rejection of 96.42%. Furthermore, this optimized membrane nanochannel demonstrates enhanced stability under varying external conditions compared to the original GO. This study provides useful information for the design of chemical conversion agents for GO nanochannel stabilization and the development of nanochannel membranes for precise separation.

14.
Genome Biol ; 25(1): 102, 2024 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-38641822

RESUMO

BACKGROUND: Splicing factors are vital for the regulation of RNA splicing, but some have also been implicated in regulating transcription. The underlying molecular mechanisms of their involvement in transcriptional processes remain poorly understood. RESULTS: Here, we describe a direct role of splicing factor RBM22 in coordinating multiple steps of RNA Polymerase II (RNAPII) transcription in human cells. The RBM22 protein widely occupies the RNAPII-transcribed gene locus in the nucleus. Loss of RBM22 promotes RNAPII pause release, reduces elongation velocity, and provokes transcriptional readthrough genome-wide, coupled with production of transcripts containing sequences from downstream of the gene. RBM22 preferentially binds to the hyperphosphorylated, transcriptionally engaged RNAPII and coordinates its dynamics by regulating the homeostasis of the 7SK-P-TEFb complex and the association between RNAPII and SPT5 at the chromatin level. CONCLUSIONS: Our results uncover the multifaceted role of RBM22 in orchestrating the transcriptional program of RNAPII and provide evidence implicating a splicing factor in both RNAPII elongation kinetics and termination control.


Assuntos
Fator B de Elongação Transcricional Positiva , RNA Polimerase II , Humanos , Cromatina , Fator B de Elongação Transcricional Positiva/genética , Fator B de Elongação Transcricional Positiva/metabolismo , RNA Polimerase II/metabolismo , Splicing de RNA , Fatores de Processamento de RNA/genética , Transcrição Gênica , Fatores de Elongação da Transcrição/genética , Fatores de Elongação da Transcrição/metabolismo
15.
Int J Biol Macromol ; 269(Pt 1): 131875, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38677701

RESUMO

The aim of this study was to develop novel konjac glucomannan (KGM)-based highly antibacterial active films, where five types of films were prepared and compared. The microstructure results showed that KGM-based films loaded with thyme essential oil (TEO) through bacterial cellulose nanofibers/Ag nanoparticles (BCNs/Ag nanoparticles) stabilized Pickering emulsions (Type V films) displayed the smoothest surface and the most evenly dispersed TEO droplets as compared with the other four types of films. Moreover, Type V films showed the highest contact angle value (86.28°), the best thermal stability and mechanical properties. Furthermore, Type V films presented the highest total phenol content (13.23 mg gallic acid equivalent/g film) and the best antioxidant activity (33.96 %) as well as the best sustained-release property, thus showing the best antibacterial activity, which was probably due to that BCNs/Ag nanoparticles and TEO displayed a synergistic effect to some extent. Consequently, Type V film-forming solutions were used as coatings for tangerines. The results showed that the tangerines treated with Type V coatings displayed excellent fresh-keeping properties. Therefore, the coatings, KGM-based film-forming solutions loaded with TEO through BCNs/Ag nanoparticles stabilized Pickering emulsions, have great potential for the preservation of fruits and vegetables.


Assuntos
Antibacterianos , Celulose , Emulsões , Mananas , Nanopartículas Metálicas , Nanofibras , Óleos Voláteis , Prata , Thymus (Planta) , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Nanofibras/química , Mananas/química , Celulose/química , Emulsões/química , Thymus (Planta)/química , Prata/química , Nanopartículas Metálicas/química , Antioxidantes/química , Antioxidantes/farmacologia , Testes de Sensibilidade Microbiana
16.
Spine J ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38614156

RESUMO

BACKGROUND CONTEXT: A subgroup of patients with pelvic anteversion can present with an unusually large degree of lumbar lordosis (LL), a highly sloped sacrum, and a relatively small pelvic incidence (PI). Prior to lumbar surgery, it can be important to consider such unique sagittal alignment. However, until now, there has been a lack of a predictive model considering different pelvic alignments. Furthermore, the dynamic characteristics of an anteverted pelvis (AP) subgroup have also been unclear. PURPOSE: To build linear predictive formulas for LL that take pelvic anteversion into consideration and to explore the dynamic characteristics of an AP subgroup. STUDY DESIGN: Monocentric, cross-sectional study. PATIENT SAMPLE: Five hundred and sixty-five asymptomatic Chinese men and women between the ages of 18 and 80 years. OUTCOME MEASURES: Sagittal parameters including LL, lumbar lordosis minus thoracic kyphosis (LL-TK), PI, pelvic tilt (PT), pelvic incidence minus lumbar lordosis (PI-LL), sacral slope (SS), sacral slope divided by pelvic incidence (SS/PI), sagittal vertical axis (SVA), thoracic kyphosis (TK), and T1 (first thoracic vertebra) pelvic angle (TPA) were measured on whole spine radiographs obtained with participants in standing and sitting positions. METHODS: All participants underwent radiography in the standing position; 235 of them underwent additional radiography in the sitting position to allow measurement of sagittal parameters. The participants with pelvic anteversion were placed in an AP (anteverted pelvis) group. Sagittal parameters were compared between the AP group and the non-AP group, and predictive formulas for LL based on PI were created in both groups. In addition, changes in sagittal parameters from standing to sitting were compared in the AP group and a PI-matched control group. RESULTS: Of the 565 participants, 171 (30.3%) had pelvic anteversion. In comparison with the non-AP group, the AP group presented with larger LL, a larger SS, and a smaller PT, with relatively small PI. The predictive formulas for LL were LL=0.60° × PI+21.60° (R2=0.268; p<.001) in the whole cohort, LL=0. 83×PI+18.75° (R2=0.427; p<.001) in AP group, and LL=0.79°×PI+9.66° (R2=0.451; p<.001) in the non-AP group. In moving from standing to sitting, the AP group presented with a larger decrease in SS and LL compared with the control group, indicating different patterns of spinopelvic motion. CONCLUSIONS: In the cohort examined, 30.3% present with pelvic anteversion. Those with AP present with unique characteristics of spinopelvic alignment. In moving from standing to sitting, they exhibit different patterns of spinopelvic motion. We found that identifying the degree of anteversion in each person improves the accuracy of linear models for predicting the degree of LL, which in turn can make plans for spine surgery more accurate.

17.
Biomed Pharmacother ; 174: 116447, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38518606

RESUMO

Sepsis-induced acute respiratory distress syndrome (ARDS) causes significant fatalities worldwide and lacks pharmacological intervention. Alveolar fluid clearance (AFC) plays a pivotal role in the remission of ARDS and is markedly impaired in the pathogenesis of ARDS. Here, we demonstrated that erythropoietin could effectively ameliorate lung injury manifestations and lethality, restore lung function and promote AFC in a rat model of lipopolysaccharide (LPS)-induced ARDS. Moreover, it was proven that EPO-induced restoration of AFC occurs through triggering the total protein expression of ENaC and Na,K-ATPase channels, enhancing their protein abundance in the membrane, and suppressing their ubiquitination for degeneration. Mechanistically, the data indicated the possible involvement of EPOR/JAK2/STAT3/SGK1/Nedd4-2 signaling in this process, and the pharmacological inhibition of the pathway markedly eliminated the stimulating effects of EPO on ENaC and Na,K-ATPase, and subsequently reversed the augmentation of AFC by EPO. Consistently, in vitro studies of alveolar epithelial cells paralleled with that EPO upregulated the expression of ENaC and Na,K-ATPase, and patch-clamp studies further demonstrated that EPO substantially strengthened sodium ion currents. Collectively, EPO could effectively promote AFC by improving ENaC and Na,K-ATPase protein expression and abundance in the membrane, dependent on inhibition of ENaC and Na,K-ATPase ubiquitination, and resulting in diminishing LPS-associated lung injuries.


Assuntos
Canais Epiteliais de Sódio , Eritropoetina , Ratos Sprague-Dawley , Síndrome do Desconforto Respiratório , Sepse , ATPase Trocadora de Sódio-Potássio , Ubiquitinação , Animais , Canais Epiteliais de Sódio/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismo , Eritropoetina/farmacologia , Sepse/complicações , Sepse/tratamento farmacológico , Sepse/metabolismo , Ubiquitinação/efeitos dos fármacos , Síndrome do Desconforto Respiratório/tratamento farmacológico , Síndrome do Desconforto Respiratório/metabolismo , Masculino , Ratos , Alvéolos Pulmonares/efeitos dos fármacos , Alvéolos Pulmonares/metabolismo , Alvéolos Pulmonares/patologia , Lipopolissacarídeos , Transdução de Sinais/efeitos dos fármacos , Modelos Animais de Doenças
18.
Opt Lett ; 49(3): 526-529, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38300050

RESUMO

Heterodyne interferometry is a powerful tool for achieving high precision and fast measurement. We developed an angle measurement system based on heterodyne interferometry by combining discrete equal-spacing longitudinal modes of optical frequency comb with an acousto-optic modulator. Using a self-designed grating-corner-cube sensor, this method can achieve a two-dimensional angle measurement with sub-arcsecond accuracy and megahertz (MHz) update rate. We experimentally demonstrate a precision of 0.073 arcsec under a 3 MHz update rate, and comparison residuals are kept within 0.063 arcsec over 300 arcsec when compared to a piezo stage. In the dynamic measurement of a 40 Hz frequency, the continuous sinusoidal motion of 0.05 arcsec can be clearly distinguished and reconstructed.

19.
BioData Min ; 17(1): 6, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38408995

RESUMO

BACKGROUND: Previous studies have shown an association between gut microbiota and cardiovascular diseases (CVDs). However, the underlying causal relationship remains unclear. This study aims to elucidate the causal relationship between gut microbiota and CVDs and to explore the pathogenic role of gut microbiota in CVDs. METHODS: In this two-sample Mendelian randomization study, we used genetic instruments from publicly available genome-wide association studies, including single-nucleotide polymorphisms (SNPs) associated with gut microbiota (n = 14,306) and CVDs (n = 2,207,591). We employed multiple statistical analysis methods, including inverse variance weighting, MR Egger, weighted median, MR pleiotropic residuals and outliers, and the leave-one-out method, to estimate the causal relationship between gut microbiota and CVDs. Additionally, we conducted multiple analyses to assess horizontal pleiotropy and heterogeneity. RESULTS: GWAS summary data were available from a pooled sample of 2,221,897 adult and adolescent participants. Our findings indicated that specific gut microbiota had either protective or detrimental effects on CVDs. Notably, Howardella (OR = 0.955, 95% CI: 0.913-0.999, P = .05), Intestinibacter (OR = 0.908, 95% CI:0.831-0.993, P = .03), Lachnospiraceae (NK4A136 group) (OR = 0.904, 95% CI:0.841-0.973, P = .007), Turicibacter (OR = 0.904, 95% CI: 0.838-0.976, P = .01), Holdemania (OR, 0.898; 95% CI: 0.810-0.995, P = .04) and Odoribacter (OR, 0.835; 95% CI: 0.710-0.993, P = .04) exhibited a protective causal effect on atrial fibrillation, while other microbiota had adverse causal effects. Similar effects were observed with respect to coronary artery disease, myocardial infarction, ischemic stroke, and hypertension. Furthermore, reversed Mendelian randomization analyses revealed that atrial fibrillation and ischemic stroke had causal effects on certain gut microbiotas. CONCLUSION: Our study underscored the importance of gut microbiota in the context of CVDs and lent support to the hypothesis that increasing the abundance of probiotics or decreasing the abundance of harmful bacterial populations may offer protection against specific CVDs. Nevertheless, further research is essential to translate these findings into clinical practice.

20.
Bioact Mater ; 35: 447-460, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38390527

RESUMO

Atherosclerosis is featured as chronic low-grade inflammation in the arteries, which leads to the formation of plaques rich in lipids. M2 macrophage-derived extracellular vesicles (M2EV) have significant potential for anti-atherosclerotic therapy. However, their therapeutic effectiveness has been hindered by their limited targeting capability in vivo. The objective of this study was to create the P-M2EV (platelet membrane-modified M2EV) using the membrane fusion technique in order to imitate the interaction between platelets and macrophages. P-M2EV exhibited excellent physicochemical properties, and microRNA (miRNA)-sequencing revealed that the extrusion process had no detrimental effects on miRNAs carried by the nanocarriers. Remarkably, miR-99a-5p was identified as the miRNA with the highest expression level, which targeted the mRNA of Homeobox A1 (HOXA1) and effectively suppressed the formation of foam cells in vitro. In an atherosclerotic low-density lipoprotein receptor-deficient (Ldlr-/-) mouse model, the intravenous injection of P-M2EV showed enhanced targeting and greater infiltration into atherosclerotic plaques compared to regular extracellular vesicles. Crucially, P-M2EV successfully suppressed the progression of atherosclerosis without causing systemic toxicity. The findings demonstrated a biomimetic platelet-mimic system that holds great promise for the treatment of atherosclerosis in clinical settings.

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