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1.
Food Chem ; 457: 140067, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38959681

RESUMO

Round green tea (RGT) presents unique properties and is widely distributed in China, and during processing, it undergoes dynamic changes in non-volatile metabolites (NVMs), which are poorly understood. Utilizing UHPLC-Q-Exactive/MS analysis, this study comprehensively characterized 216 NVMs during RGT processing and identified fixation and pan-frying as key processes influencing NVMs. Additionally, 23 key differential NVMs were screened, with amino acid and flavonoid metabolism highlighted as key metabolic pathways for RGT taste and color quality. The impact of pan-frying degree on shape, color, and taste was also explored. Moderate pan-frying led to optimal results, including a tight and round shape, green and bright color, mellow and umami taste, and reduced astringent and bitter taste NVMs, including epigallocatechin gallate, procyanidin B2, myricetin 3-O-galactoside, quinic acid, strictinin, phenylalanine, and theobromine. This study addresses the NVM research gap in RGT processing, thus providing a technical foundation for the precision-oriented processing of high-quality tea.

2.
Ann Hematol ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958702

RESUMO

This study aims to analyze the risk factors for the development of multidrug-resistant (MDR) and carbapenem-resistant (CR) bacteria bloodstream infection (BSI) in a patient with acute leukemia (AL) and the mortality in gram-negative bacteria (GNB) BSI. This is a retrospective study conducted at West China Hospital of Sichuan University, which included patients diagnosed with AL and concomitant GNB BSI from 2016 to 2021. A total of 206 patients with GNB BSI in AL were included. The 30-day mortality rate for all patients was 26.2%, with rates of 25.8% for those with MDR GNB BSI and 59.1% for those with CR GNB BSI. Univariate and multivariate analyses revealed that exposure to quinolones (Odds ratio (OR) = 3.111, 95% confidence interval (95%CI): 1.623-5.964, p = 0.001) within the preceding 30 days was an independent risk factor for MDR GNB BSI, while placement of urinary catheter (OR = 6.311, 95%CI: 2.478-16.073, p < 0.001) and exposure to cephalosporins (OR = 2.340, 95%CI: 1.090-5.025, p = 0.029) and carbapenems (OR = 2.558, 95%CI: 1.190-5.497, p = 0.016) within the preceding 30 days were independently associated with CR GNB BSI. Additionally, CR GNB BSI (OR = 2.960, 95% CI: 1.016-8.624, p = 0.047), relapsed/refractory AL (OR = 3.035, 95% CI: 1.265-7.354, p = 0.013), septic shock (OR = 5.108, 95% CI: 1.794-14.547, p = 0.002), platelets < 30 × 109/L before BSI (OR = 7.785, 95% CI: 2.055-29.492, p = 0.003), and inappropriate empiric antibiotic therapy (OR = 3.140, 95% CI: 1.171-8.417, p = 0.023) were independent risk factors for 30-day mortality in AL patients with GNB BSI. Prior antibiotic exposure was a significant factor in the occurrence of MDR GNB BSI and CR GNB BSI. CR GNB BSI increased the risk of mortality in AL patients with GNB BSI.

3.
Mitochondrial DNA B Resour ; 9(7): 911-914, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39077061

RESUMO

Cirriformia species usually inhabit intertidal zones and deep-sea sediments. Their accurate identification has proven to be challenging. Here, we present the complete mitochondrial genome of one Cirriformia tentaculata_Montagu 1808 specimen collected from China. The total length of the complete mitochondrial sequence of C. tentaculata is 15,516 bp and consists of 13 protein-coding genes (PCGs), 23 tRNA genes, two rRNA genes, and an A + T rich region (64.20%). All PCGs begin with the typical ATN start codon, except for cox1, which uses TTG. TAA or TAG serve as termination codons for twelve PCGs, while nad5 terminates with an incomplete codon, T. The phylogenetic tree revealed a close relationship between C. tentaculata in this study, and Cirriformia cf. tentaculata and Timarete posteria from Korea. The information will assist in the future identification and understanding of this species and offers a novel point of reference for identifying Cirriformia species, and phylogenetic studies.

4.
Small ; : e2402715, 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39004872

RESUMO

Messenger RNA (mRNA) is an emerging class of therapeutic agents for treating a wide range of diseases. However, due to the instability and low cell transfection rate of naked mRNA, the expression of delivered mRNA in target cells or tissues in vivo requires delivery strategies. Biomimetic vectors hold advantages such as high biocompatibility, tissue specific targeting ability and efficient delivery mechanisms, potentially overcoming challenges faced by other delivery vectors. In this review, biomimetic vector-based mRNA delivery systems are summarized and discuss the possible challenges and prospects of such delivery systems, which may contribute to the progress and application of mRNA-based therapy in the biomedical field.

5.
Molecules ; 29(13)2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38999045

RESUMO

1,4-diaminobutane is widely used in the industrial production of polymers, pharmaceuticals, agrochemicals and surfactants. Owing to economic and environmental concerns, there has been a growing interest in using microbes to produce 1,4-diaminobutane. However, there is lack of research on the influence of cofactors pyridoxal phosphate (PLP) and NADPH on the synthesis of 1,4-diaminobutane. PLP serves as a cofactor of ornithine decarboxylase in the synthesis of 1,4-diaminobutane. Additionally, the synthesis of 1 mol 1,4-diaminobutane requires 2 mol NADPH, thus necessitating consideration of NADPH balance in the efficient synthesis of 1,4-diaminobutane by Escherichia coli. The aim of this study was to enhance the synthesis efficiency of 1,4-diaminobutane through increasing production of PLP and NADPH. By optimizing the expression of the genes associated with synthesis of PLP and NADPH in E. coli, cellular PLP and NADPH levels increased, and the yield of 1,4-diaminobutane also increased accordingly. Ultimately, using glucose as the primary carbon source, the yield of 1,4-diaminobutane in the recombinant strain NAP19 reached 272 mg/L·DCW, by increased 79% compared with its chassis strain.


Assuntos
Escherichia coli , NADP , Fosfato de Piridoxal , Escherichia coli/genética , Escherichia coli/metabolismo , Fosfato de Piridoxal/metabolismo , NADP/metabolismo , Glucose/metabolismo , Engenharia Metabólica/métodos
6.
Biosens Bioelectron ; 263: 116582, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39038401

RESUMO

This study develops a series of NBI-based acidochromic AIEgens engineered for ultra-wide acidochromic scope in self-reporting soft actuators, establishing the relationship between the photophysical properties and structural configurations of the AIEgens, further investigating their acidochromic behavior and fabricating acidity monitoring chips. The acidochromic behaviors were thoroughly investigated, and high-precision acidity monitoring chips were fabricated. We confirmed the protonation order of nitrogen atoms within the molecules and elucidated the acidochromic mechanisms through DFT and 1H NMR analyses. Utilizing these findings, we designed acid-driven hydrogel-based biomimetic actuators that can self-report and control the release of heavy loads under acidic conditions. These actuators hold significant potential for applications in targeted drug delivery within acidic biological environments, controlled release systems, and specialized transportation of heavy loads under acidic conditions.

7.
Front Psychol ; 15: 1417557, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39035086

RESUMO

Introduction: Representations in working memory can affect distractor suppression in human visual search, and this process is modulated by a separate top-down cognitive control. An increasing body of research has demonstrated that patients with substance use disorder (SUD) have deficits in cognitive control over filtering interference by perceptual distractors. However, their ability to resist proactive interference from working memory has received comparatively less attention. Methods: Here, we investigate this issue by employing a working memory/visual search dual-task paradigm. An intervening gap-location search task was instructed to be performed while participants memorized a written color word, with congruent auditory information present during the memory encoding phase on half of the trials. Results: Results showed that there was a reliable response time (RT) advantage when the meaning of the memory sample agreed with the color of one of the distractors under the visual alone condition. However, such a result was only found in the control group. More importantly, both groups exhibited comparable facilitation under the audiovisual condition, with the facilitation effect appearing later in the SUD group. Furthermore, the facilitation effect was superior in magnitude and time course under the audiovisual condition to the visual alone condition. Discussion: These findings highlight how patients with SUD resist distractor interference at the memory level and extend our understanding of how working memory, selective attention, and audiovisual enhancement interact to optimize perceptual decisions in patients with SUD.

8.
World J Urol ; 42(1): 370, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38847900

RESUMO

PURPOSE: The objective was to evaluate the efficacy of transcutaneous electrical nerve stimulation (TENS) combined with mirabegron therapy compared with mirabegron monotherapy in the treatment of female patients with overactive bladder (OAB). METHODS: In this randomized controlled study, 100 female outpatients with OAB were screened. Among these patients, 86 who met the inclusion criteria were randomly divided into the TENS combined with mirabegron treatment group and mirabegron monotherapy treatment group, with 43 patients in each group. The voiding diary, Overactive Bladder Symptom Score (OABSS), Overactive Bladder Questionnaire Symptom Bother Score (OAB-q SBS), total health-related quality of life (OAB-q HRQoL), and treatment satisfaction-visual analog scale (TS-VAS) score before and after treatment were recorded to evaluate the efficacy of OAB treatment. Seventy-nine of the 86 patients (40 in the TENS plus mirabegron group and 39 in the mirabegron monotherapy group) completed 12 weeks of treatment. RESULTS: TENS combined with mirabegron therapy was superior to mirabegron monotherapy in improving the primary endpoints, including the daily number of micturition episodes and the daily MVV/micturition and secondary endpoints, including the daily number of urgency episodes, the OABSS, the OAB-q SBS, the HRQoL score and TS-VAS score. There were no statistically significant differences in urgency urinary incontinence and nocturia between the groups. Some minor adverse effects were observed, including muscle pain, local paresthesia and constipation. CONCLUSIONS: The combination of TENS and mirabegron was more effective than mirabegron alone in the treatment of female patients with OAB. TRIAL REGISTRATION NUMBER: ChiCTR2400080528 (31.01.2024, retrospectively registered).


Assuntos
Acetanilidas , Tiazóis , Estimulação Elétrica Nervosa Transcutânea , Bexiga Urinária Hiperativa , Humanos , Bexiga Urinária Hiperativa/terapia , Bexiga Urinária Hiperativa/tratamento farmacológico , Feminino , Acetanilidas/uso terapêutico , Tiazóis/uso terapêutico , Estimulação Elétrica Nervosa Transcutânea/métodos , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Terapia Combinada , Idoso , Adulto , Agonistas de Receptores Adrenérgicos beta 3/uso terapêutico , Agentes Urológicos/uso terapêutico
9.
J Acupunct Meridian Stud ; 17(3): 100-109, 2024 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-38898647

RESUMO

Importance: Post-stroke sialorrhea (PSS) refers to excessive saliva flowing out the lip border after a stroke. PSS negatively affects patient self-image and social communication and may lead to depression. Limited evidence supports the link between excessive salivation and PSS. No large-scale, strictly controlled randomized controlled trials have shown the effectiveness of acupuncture in treating PSS patients. Objective: We aim to compare the effects of intraoral and sham acupuncture in PSS patients and explore relationships among salivation and drooling severity and frequency and swallowing function in stroke patients. Design: Clinical study protocol, SPIRIT compliant. Setting: Prospective, single-center, randomized, and sham-controlled trial. Population: We will recruit 106 PSS patients to receive 4-week intraoral or sham acupuncture. Additionally, 53 stroke patients without PSS will undergo a conventional 4-week treatment program to compare salivation between PSS and non-PSS patients. Exposures: Intraoral or sham acupuncture. Main Outcomes and Measures: The main evaluation index will be the 3-minute saliva weight (3MSW), comparing changes in 3MSW from baseline to weeks 4 and 8. Secondary assessment indices will include the "Drooling Severity and Frequency Scale" and "Functional Oral Intake Scale." Results: The results from this study will be published in peer-reviewed journals. Conclusion: Comparing effects of intraoral and sham acupuncture in PSS patients, this study may contribute important evidence for future PSS treatment and provide valuable insights into whether salivation issues in stroke patients are attributed to heightened salivary secretion or dysphagia.


Assuntos
Terapia por Acupuntura , Sialorreia , Acidente Vascular Cerebral , Humanos , Sialorreia/terapia , Sialorreia/etiologia , Terapia por Acupuntura/métodos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia , Acidente Vascular Cerebral/fisiopatologia , Masculino , Estudos Prospectivos , Feminino , Salivação , Adulto , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
J Acoust Soc Am ; 155(6): 3968-3982, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38921645

RESUMO

Tone detection is crucial for passive sonar systems. Numerous algorithms have been developed for passive tone detection, but their effectiveness in detecting weak tones is still limited. To enhance noise resilience in passive tone detection, a broad-receptive field complex-valued structure named attention-driven complex-valued U-Net is proposed. Concretely, two attention mechanisms, namely, temporal attention and harmonic attention, are proposed to broaden the receptive field with high computational efficiency. Complex-valued operators are then introduced to mine both amplitude and phase information of tones. Additionally, a symmetric downsampling and upsampling strategy is proposed to improve the reconstruction accuracy of detailed time-frequency information. Overall, the proposed method demonstrates a strong robustness to noise and a strong ability to generalize. Experimental results on both simulated data and real-world data validate the superiority of the proposed attention-driven complex-valued U-Net against conventional U-shaped structures.

11.
Food Chem X ; 23: 101519, 2024 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-38933990

RESUMO

In the present study, the comprehensive quality of Congou black tea (CBT) including aroma, taste, and liquid color was investigated by a combination of gas chromatography electronic nose (GC-E-Nose), electronic tongue (E-tongue), and electronic eye (E-eye). An excellent discrimination of different quality grades of CBT was accomplished through the fusion of GC-E-Nose, E-tongue, and E-eye combined with orthogonal partial least squares discriminant analysis, with parameters of R2Y = 0.803 and Q2 = 0.740. Moreover, the quantitative evaluation of CBT quality was successfully achieved by partial least squares regression analysis, with the absolute error within 1.39 point, and the relative error within 1.62%. Additionally, 12 key variables were screened out by stepwise multiple linear regression analysis, which significantly contributed to the comprehensive quality score of CBT. Our results suggest that the fusion of multiple intelligent sensory technologies offers great potential and practicability in the quality evaluation of black tea.

12.
Food Chem ; 458: 140226, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38943961

RESUMO

Shaking constitutes a pivotal technique for enhancing black tea quality; nevertheless, its impact on the transformation mechanism of non-volatile metabolites (NVMs) in black tea remains obscure. The present study aimed to investigate the impact of shaking-withering methods (SWM) and traditional-withering methods (TWM) on black tea quality and NVMs conversion. A total of 57 NVMs and 14 objective quantitative indicators were obtained. SWM enhanced sweetness and umami taste, as well as appearance and liquor color brightness of black tea. Eight key differential NVMs were identified by multivariate statistical and dose over threshold value analysis. Metabolic pathway and evolution law analysis revealed that SWM enhanced the oxidation of catechins and flavonol glycosides, promoted the decarboxylation of glutamic acid, then facilitated the formation of theaflavin-3,3'-digallate, finally enhanced the taste and color quality of black tea. This study offers theoretical guidance and technical support for the targeted processing of high-quality black tea.

13.
J Hazard Mater ; 475: 134580, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38865829

RESUMO

In this research, a new material, chitosan/polypyrrole (CS/PPy), was synthesized and linked with the Cr(VI)-reducing bacterial strain YL3 to treat Cr(VI)-polluted soil. The findings demonstrated that the synergistic application of strain YL3 and CS/PPy achieved the greatest reduction (99.6 %). During the remediation process, CS/PPy served as a mass-storage and sustained release agent in the soil, which initially decreased the toxic effects of high concentrations of Cr(VI) on strain YL3, thereby enhancing the Cr(VI) reduction efficiency of strain YL3. These combined effects significantly mitigated Cr(VI) stress in the soil and restored enzyme activities. Furthermore, wheat growth in the treated soil also significantly improved. High-throughput sequencing of the microorganisms in the treated soil revealed that CS/PPy was not only effective at removing Cr(VI) but also at preserving the original microbial diversity of the soil. This suggests that the combined treatment using strain YL3 and CS/PPy could rehabilitate Cr(VI)-contaminated soil, positioning CS/PPy as a promising composite material for future bioremediation efforts in Cr(VI)-contaminated soils.


Assuntos
Biodegradação Ambiental , Quitosana , Cromo , Microbacterium , Polímeros , Pirróis , Microbiologia do Solo , Poluentes do Solo , Poluentes do Solo/metabolismo , Cromo/metabolismo , Cromo/química , Quitosana/química , Polímeros/química , Polímeros/metabolismo , Pirróis/metabolismo , Pirróis/química , Microbacterium/metabolismo , Triticum/metabolismo
14.
Food Chem ; 455: 139844, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-38823134

RESUMO

In this study, a sensitive dual-signal electrochemiluminescence (ECL) immunosensor was developed for okadaic acid (OA) detection utilizing copper nanoclusters (CuNCs) and Ru(bpy)32+-doped silica nanoparticles (RuSiNPs). Interestingly, the CuNCs could simultaneously enhance both cathodic (-0.95 V) and anodic (+1.15 V) ECL signals of RuSiNPs, forming a dual-signal ECL sensing platform. Further, RuSiNPs@CuNCs were used as immunomarkers by covalently conjugating them with an anti-OA monoclonal antibody (mAb) to form probes. Finally, dual ECL signals of the immunosensor were fabricated and showed good linear relationships with OA concentrations in the range of 0.05-70 ng mL-1, having a median inhibitory concentration (IC50) of 1.972 ng mL-1 and a limit of detection of 0.039 ng mL-1. Moreover, the constant ratio of the cathodic and anodic ECL peaks achieved self-calibration of the detection signal and improved the reliability of the results. Finally, we successfully applied the ECL sensor to detect OA in spiked oyster samples.


Assuntos
Cobre , Técnicas Eletroquímicas , Medições Luminescentes , Ácido Okadáico , Dióxido de Silício , Cobre/química , Dióxido de Silício/química , Medições Luminescentes/métodos , Medições Luminescentes/instrumentação , Ácido Okadáico/análise , Nanopartículas/química , Animais , Técnicas Biossensoriais , Limite de Detecção , Imunoensaio/métodos , Imunoensaio/instrumentação , Nanopartículas Metálicas/química
15.
Cancer Immunol Immunother ; 73(8): 143, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38832955

RESUMO

This study investigates the role of USP47, a deubiquitinating enzyme, in the tumor microenvironment and its impact on antitumor immune responses. Analysis of TCGA database revealed distinct expression patterns of USP47 in various tumor tissues and normal tissues. Prostate adenocarcinoma showed significant downregulation of USP47 compared to normal tissue. Correlation analysis demonstrated a positive association between USP47 expression levels and infiltrating CD8+ T cells, neutrophils, and macrophages, while showing a negative correlation with NKT cells. Furthermore, using Usp47 knockout mice, we observed a slower tumor growth rate and reduced tumor burden. The absence of USP47 led to increased infiltration of immune cells, including neutrophils, macrophages, NK cells, NKT cells, and T cells. Additionally, USP47 deficiency resulted in enhanced activation of cytotoxic T lymphocytes (CTLs) and altered T cell subsets within the tumor microenvironment. These findings suggest that USP47 plays a critical role in modulating the tumor microenvironment and promoting antitumor immune responses, highlighting its potential as a therapeutic target in prostate cancer.


Assuntos
Linfócitos do Interstício Tumoral , Neoplasias da Próstata , Animais , Humanos , Masculino , Camundongos , Linhagem Celular Tumoral , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Microambiente Tumoral
16.
Poult Sci ; 103(7): 103835, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38772092

RESUMO

Avian leukemia virus subgroup J (ALV-J) and chicken infectious anemia virus (CIAV) can be vertically transmitted; however, the pathogenicity of vertically transmitted coinfection with these 2 pathogens has not been studied. In this study, we created a model of chick morbidity in which chicks carried either ALV-J, CIAV, or both viruses via embryo inoculation. Thereafter, we analyzed the effects of vertically transmitted coinfection with CIAV and ALV-J on the pathogenicity of ALV-J and performed a purification assay based on hatching, mortality viremia positivity, and detection of fecal ALV-p27 antigen rates, and body weight. The hatching rate of the ALV-J+CIAV group was 68.57%, lower than those of the single infection and control groups. The survival curve showed that the mortality rates of the CIAV and ALV-J coinfection groups were higher than those of the single infection and control groups. Body weight statistics showed that coinfection aggravated the 7-d growth inhibition effect. The results of ALV-p27 antigen detection in cell culture supernatants showed that the positivity rates of the ALV-J and ALV-J+CIAV groups were 100% at all ages and 0% in the control group. The results of ALV-p27 antigen detection by anal swabs showed that the positivity rates of the ALV-J group were 92.86, 90.90, 88.89, and 93.33% at all ages, and that the ALV-J p27 positivity detection rate of anal swabs was lower than that of plasma virus isolation. The immune organ index of the ALV-J+CIAV group was significantly or very significantly lower than those of the single infection and control groups. The immune organ viral load showed that coinfection with CIAV and ALV-J promoted the proliferation of ALV-J and CIAV in immune organs. Coinfection with ALV-J and CIAV reduced chicken embryo hatchability and increased chick mortality and growth inhibition relative to their respective single infections. Additionally, coinfection with ALV-J + CIAV was even more detrimental in inducing immune organ atrophy (e.g., the thymus, spleen, and bursa), and promoted individual virus replication during coinfection.


Assuntos
Vírus da Leucose Aviária , Leucose Aviária , Vírus da Anemia da Galinha , Galinhas , Infecções por Circoviridae , Coinfecção , Transmissão Vertical de Doenças Infecciosas , Doenças das Aves Domésticas , Animais , Vírus da Leucose Aviária/fisiologia , Vírus da Leucose Aviária/patogenicidade , Galinhas/virologia , Leucose Aviária/virologia , Coinfecção/veterinária , Coinfecção/virologia , Doenças das Aves Domésticas/virologia , Vírus da Anemia da Galinha/fisiologia , Vírus da Anemia da Galinha/patogenicidade , Infecções por Circoviridae/veterinária , Infecções por Circoviridae/virologia , Transmissão Vertical de Doenças Infecciosas/veterinária , Virulência , Embrião de Galinha
17.
J Am Coll Cardiol ; 83(18): 1743-1755, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38692827

RESUMO

BACKGROUND: Lipoprotein(a) (Lp[a]) is associated with an increased risk of myocardial infarction (MI). However, the mechanism underlying this association has yet to be fully elucidated. OBJECTIVES: This multicenter study aimed to investigate whether association between Lp(a) and MI risk is reinforced by the presence of low-attenuation plaque (LAP) identified by coronary computed tomography angiography (CCTA). METHODS: In a derivation cohort, a total of 5,607 patients with stable chest pain suspected of coronary artery disease who underwent CCTA and Lp(a) measurement were prospectively enrolled. In validation cohort, 1,122 patients were retrospectively collected during the same period. High Lp(a) was defined as Lp(a) ≥50 mg/dL. The primary endpoint was a composite of time to fatal or nonfatal MI. Associations were estimated using multivariable Cox proportional hazard models. RESULTS: During a median follow-up of 8.2 years (Q1-Q3: 7.2-9.3 years), the elevated Lp(a) levels were associated with MI risk (adjusted HR [aHR]: 1.91; 95% CI: 1.46-2.49; P < 0.001). There was a significant interaction between Lp(a) and LAP (Pinteraction <0.001) in relation to MI risk. When stratified by the presence or absence of LAP, Lp(a) was associated with MI in patients with LAP (aHR: 3.03; 95% CI: 1.92-4.76; P < 0.001). Mediation analysis revealed that LAP mediated 73.3% (P < 0.001) for the relationship between Lp(a) and MI. The principal findings remained unchanged in the validation cohort. CONCLUSIONS: Elevated Lp(a) augmented the risk of MI during 8 years of follow-up, especially in patients with LAP identified by CCTA. The presence of LAP could reinforce the relationship between Lp(a) and future MI occurrence.


Assuntos
Angiografia por Tomografia Computadorizada , Lipoproteína(a) , Infarto do Miocárdio , Placa Aterosclerótica , Humanos , Masculino , Feminino , Lipoproteína(a)/sangue , Infarto do Miocárdio/sangue , Infarto do Miocárdio/epidemiologia , Pessoa de Meia-Idade , Placa Aterosclerótica/sangue , Placa Aterosclerótica/diagnóstico por imagem , Idoso , Angiografia Coronária , Estudos Retrospectivos , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/epidemiologia , Estudos Prospectivos , Seguimentos , Biomarcadores/sangue
18.
Oncol Res ; 32(4): 753-768, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38560563

RESUMO

Multiple myeloma (MM) is a hematologic malignancy notorious for its high relapse rate and development of drug resistance, in which cell adhesion-mediated drug resistance plays a critical role. This study integrated four RNA sequencing datasets (CoMMpass, GSE136337, GSE9782, and GSE2658) and focused on analyzing 1706 adhesion-related genes. Rigorous univariate Cox regression analysis identified 18 key prognosis-related genes, including KIF14, TROAP, FLNA, MSN, LGALS1, PECAM1, and ALCAM, which demonstrated the strongest associations with poor overall survival (OS) in MM patients. To comprehensively evaluate the impact of cell adhesion on MM prognosis, an adhesion-related risk score (ARRS) model was constructed using Lasso Cox regression analysis. The ARRS model emerged as an independent prognostic factor for predicting OS. Furthermore, our findings revealed that a heightened cell adhesion effect correlated with tumor resistance to DNA-damaging drugs, protein kinase inhibitors, and drugs targeting the PI3K/Akt/mTOR signaling pathway. Nevertheless, we identified promising drug candidates, such as tirofiban, pirenzepine, erlotinib, and bosutinib, which exhibit potential in reversing this resistance. In vitro, experiments employing NCIH929, RPMI8226, and AMO1 cell lines confirmed that MM cell lines with high ARRS exhibited poor sensitivity to the aforementioned candidate drugs. By employing siRNA-mediated knockdown of the key ARRS model gene KIF14, we observed suppressed proliferation of NCIH929 cells, along with decreased adhesion to BMSCs and fibronectin. This study presents compelling evidence establishing cell adhesion as a significant prognostic factor in MM. Additionally, potential molecular mechanisms underlying adhesion-related resistance are proposed, along with viable strategies to overcome such resistance. These findings provide a solid scientific foundation for facilitating clinically stratified treatment of MM.


Assuntos
Mieloma Múltiplo , Humanos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/genética , Mieloma Múltiplo/patologia , Adesão Celular/genética , Fosfatidilinositol 3-Quinases/metabolismo , Prognóstico , Resistencia a Medicamentos Antineoplásicos/genética , Linhagem Celular Tumoral , Recidiva Local de Neoplasia
19.
Talanta ; 273: 125922, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38503121

RESUMO

Rapid and sensitive detection of nucleic acids has become crucial in various fields. However, most current nucleic acid detection methods can only be used in specific scenarios, such as RT-qPCR, which relies on fluorometer for signal readout, limiting its application at home or in the field due to its high price. In this paper, a universal nucleic acid detection platform combing CRISPR/Cas12a and strand displacement amplification (CRISPR-SDA) with multiple signal readout was established to adapt to different application scenarios. Nucleocapsid protein gene of SARS-CoV-2 (N gene) and hepatitis B virus (HBV) DNA were selected as model targets. The proposed strategy achieved the sensitivity of 53.1 fM, 0.15 pM, and 1 pM for N gene in fluorescence mode, personal glucose meter (PGM) mode and lateral flow assay (LFA) mode, respectively. It possessed the ability to differentiate single-base mismatch and the presence of salmon sperm DNA with a mass up to 105-fold of the targets did not significantly interfere with the assay signal. The general and modular design idea made CRISPR-SDA as simple as building blocks to construct nucleic acid sensing methods to meet different requirements by simply changing the SDA template and selecting suitable signal report probes, which was expected to find a breadth of applications in nucleic acids detection.


Assuntos
Técnicas Biossensoriais , Ácidos Nucleicos , Masculino , Humanos , Sistemas CRISPR-Cas , Sêmen , Bioensaio , DNA , Técnicas de Amplificação de Ácido Nucleico
20.
CNS Neurosci Ther ; 30(3): e14681, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38516845

RESUMO

BACKGROUND: Peroxiredoxin 2 (Prx2), an intracellular protein that regulates redox reactions, released from red blood cells is involved in inflammatory brain injury after intracerebral hemorrhage (ICH). Toll-like receptor 4 (TLR4) may be crucial in this process. This study investigated the role of the Prx2-TLR4 inflammatory axis in brain injury following experimental ICH in mice. METHODS: First, C57BL/6 mice received an intracaudate injection of autologous arterial blood or saline and their brains were harvested on day 1 to measure Prx2 levels. Second, mice received an intracaudate injection of either recombinant mouse Prx2 or saline. Third, the mice were co-injected with autologous arterial blood and conoidin A, a Prx2 inhibitor, or vehicle. Fourth, the mice received a Prx2 injection and were treated with TAK-242, a TLR4 antagonist, or saline (intraperitoneally). Behavioral tests, magnetic resonance imaging, western blot, immunohistochemistry/immunofluorescence staining, and RNA sequencing (RNA-seq) were performed. RESULTS: Brain Prx2 levels were elevated after autologous arterial blood injection. Intracaudate injection of Prx2 caused brain swelling, microglial activation, neutrophil infiltration, neuronal death, and neurological deficits. Co-injection of conoidin A attenuated autologous arterial blood-induced brain injury. TLR4 was expressed on the surface of microglia/macrophages and neutrophils and participated in Prx2-induced inflammation. TAK-242 treatment attenuated Prx2-induced inflammation and neurological deficits. CONCLUSIONS: Prx2 can cause brain injury following ICH through the TLR4 pathway, revealing the Prx2-TLR4 inflammatory axis as a potential therapeutic target.


Assuntos
Lesões Encefálicas , Sulfonamidas , Receptor 4 Toll-Like , Animais , Camundongos , Lesões Encefálicas/etiologia , Hemorragia Cerebral/metabolismo , Inflamação/etiologia , Inflamação/patologia , Camundongos Endogâmicos C57BL , Peroxirredoxinas/metabolismo , Peroxirredoxinas/farmacologia , Peroxirredoxinas/uso terapêutico , Receptor 4 Toll-Like/metabolismo
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