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1.
Comput Struct Biotechnol J ; 23: 2497-2506, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38966680

RESUMO

N-glycosylation can have a profound effect on the quality of mAb therapeutics. In biomanufacturing, one of the ways to influence N-glycosylation patterns is by altering the media used to grow mAb cell expression systems. Here, we explore the potential of machine learning (ML) to forecast the abundances of N-glycan types based on variables related to the growth media. The ML models exploit a dataset consisting of detailed glycomic characterisation of Anti-HER fed-batch bioreactor cell cultures measured daily under 12 different culture conditions, such as changes in levels of dissolved oxygen, pH, temperature, and the use of two different commercially available media. By performing spent media quantitation and subsequent calculation of pseudo cell consumption rates (termed media markers) as inputs to the ML model, we were able to demonstrate a small subset of media markers (18 selected out of 167 mass spectrometry peaks) in a Chinese Hamster Ovary (CHO) cell cultures are important to model N-glycan relative abundances (Regression - correlations between 0.80-0.92; Classification - AUC between 75.0-97.2). The performances suggest the ML models can infer N-glycan critical quality attributes from extracellular media as a proxy. Given its accuracy, we envisage its potential applications in biomaufactucuring, especially in areas of process development, downstream and upstream bioprocessing.

2.
Inorg Chem ; 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39014904

RESUMO

Aromaticity is a fundamental concept in organic chemistry. Hyperconjugative aromaticity, also known as hyperconjugation-induced aromaticity, has evolved from its origin from main group substituents to transition metal analogues, establishing itself as an important category of aromaticity. Additionally, aromatic compounds comprising two sp3-carbon atoms have recently been reported both experimentally and computationally. However, what is the maximum number of sp3-hybridized atoms needed to maintain hyperconjugative aromaticity? Here, we report that hyperconjugative aromaticity can be achieved in hexa-substituted indoliums and octa-substituted pyrroliums, possessing three-five sp3-hybridized carbon/nitrogen atoms by means of density functional theory (DFT) calculations. The aromaticity was confirmed by using various aromaticity indices, i.e., NICS, MCI, and EDDB. Notably, the strong electron-donating ability and aurophilicity of Au(I) substituents play a pivotal role in maintaining the aromaticity and structural integrity. In addition, increasing the number of hyperconjugative centers will decrease the aromaticity in these five-membered rings. Our findings highlight the significance of transition metal substituents in hyperconjugative aromaticity and offer a novel approach for designing aromatic organometallics.

3.
PLoS One ; 19(6): e0305606, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38917145

RESUMO

BACKGROUND: Insufficient exercise affects the health of patients who have implantable cardioverter defibrillators (ICD). The purpose of this study was to investigate the correlations between exercise self-efficacy (ESE) and its associated psychological factors in ICD recipients. METHODS: This cross-sectional study included individuals who had undergone ICD implantation at the cardiology department of a medical centre in Taiwan. A face-to-face survey was conducted. The survey questionnaire included questions regarding the participants' demographics, perceived health (PH), ICD shock-related anxiety (ICD-SRA), self-care self-efficacy (SSE), perceived exercise benefit (PE-benefit), perceived exercise barrier (PE-barrier), and ESE. Data were analysed using SPSS 20.0 Software. Stepwise multiple regression analyses were also performed to evaluate the predictive effects of the aforementioned factors on ESE. RESULTS: A total of 52 ICD recipients were enrolled. ESE was negatively correlated with ICD-SRA (r = -0.511; p < 0.01) and PE-barrier (r = -0.563; p < 0.01), but positively correlated with SSE (r = 0.339; p < 0.05) and PE-benefit (r = 0.464; p < 0.01). The stepwise multiple regression analysis revealed that PE-barrier, PE-benefit, and ICD-SRA effectively predicted ESE in the participants. CONCLUSIONS: ESE may be improved by overcoming PE-barrier, ICD-SRA and enhancing PE-benefit. Consequently, improving ESE may enhance the health benefits of exercise.


Assuntos
Desfibriladores Implantáveis , Exercício Físico , Autoeficácia , Humanos , Desfibriladores Implantáveis/psicologia , Masculino , Feminino , Pessoa de Meia-Idade , Exercício Físico/psicologia , Estudos Transversais , Idoso , Inquéritos e Questionários , Adulto , Ansiedade/psicologia , Taiwan , Autocuidado
4.
Sci Rep ; 14(1): 11018, 2024 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-38744902

RESUMO

Antibody-drug conjugates (ADC) payloads are cleavable drugs that act as the warhead to exert an ADC's cytotoxic effects on cancer cells intracellularly. A simple and highly sensitive workflow is developed and validated for the simultaneous quantification of six ADC payloads, namely SN-38, MTX, DXd, MMAE, MMAF and Calicheamicin (CM). The workflow consists of a short and simple sample extraction using a methanol-ethanol mixture, followed by a fast liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. The results showed that well-validated linear response ranges of 0.4-100 nM for SN38, MTX and DXd, 0.04-100 nM for MMAE and MMAF, 0.4-1000 nM for CM were achieved in mouse serum. Recoveries for all six payloads at three different concentrations (low, medium and high) were more than 85%. An ultra-low sample volume of only 5 µL of serum is required due to the high sensitivity of the method. This validated method was successfully applied to a pharmacokinetic study to quantify MMAE in mouse serum samples.


Assuntos
Imunoconjugados , Espectrometria de Massas em Tandem , Animais , Camundongos , Cromatografia Líquida/métodos , Imunoconjugados/farmacocinética , Imunoconjugados/química , Espectrometria de Massas em Tandem/métodos , Fluxo de Trabalho , Espectrometria de Massa com Cromatografia Líquida
5.
J Pediatr Nurs ; 77: 204-211, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38593571

RESUMO

PURPOSE: To explore the parent-child relationship through the subjective experience of adolescents with congenital heart disease (CHD). DESIGN AND METHODS: A descriptive phenomenology approach was adopted. Twelve adolescents aged from 12 to 18 years with CHD were recruited from the pediatric cardiology clinics at two medical centers in Taiwan. Data were collected through in-depth interviews. Data were analyzed using Colaizzi's phenomenological analysis method, and results were reported in accordance with the Consolidated Criteria for Reporting Qualitative Research guidelines. RESULTS: The experiences of the adolescents with CHD revealed five themes: 1. the enhancement of self-worth through parents' love; 2. the importance of parental support in desperate situations; 3. the development of a sense of security through mutual understanding; 4. growth under parental expectations; and 5. parental overcontrol disguised as love. CONCLUSIONS: The parent-child relationship encompasses both positive and negative experiences. Adolescents prioritize their relationship with parents over that with peers. PRACTICE IMPLICATIONS: Nurses caring for adolescents with CHD can improve care by recognizing the influence of parental love, support in challenges, mutual understanding, parental expectations, and potential negative consequences of overcontrol. This insight guides effective guidance for adolescents, enhancing parent-child interactions and overall well-being.


Assuntos
Cardiopatias Congênitas , Relações Pais-Filho , Pesquisa Qualitativa , Humanos , Adolescente , Masculino , Feminino , Cardiopatias Congênitas/psicologia , Cardiopatias Congênitas/enfermagem , Taiwan , Criança , Adaptação Psicológica , Comportamento do Adolescente/psicologia , Entrevistas como Assunto
6.
Anim Biosci ; 37(8): 1317-1332, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38665091

RESUMO

OBJECTIVE: Rare study of the non-coding and regulatory regions of the genome limits our ability to decode the mechanisms of fatty liver hemorrhage syndrome (FLHS) in chickens. METHODS: Herein, we constructed the high-fat diet-induced FLHS chicken model to investigate the genome-wide active enhancers and transcriptome by H3K27ac target chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-Seq) profiles of normal and FLHS liver tissues. Concurrently, an integrative analysis combining ChIP-seq with RNA-Seq and a comparative analysis with chicken FLHS, rat non-alcoholic fatty liver disease (NAFLD) and human NAFLD at the transcriptome level revealed the enhancer and super enhancer target genes and conservative genes involved in metabolic processes. RESULTS: In total, 56 and 199 peak-genes were identified in upregulated peak-genes positively regulated by H3K27ac (Cor (peak-gene correlation) ≥0.5 and log2(FoldChange) ≥1) (PP) and downregulated peak-genes positively regulated by H3K27ac (Cor (peak-gene correlation) ≥0.5 and log2(FoldChange)≤-1) (PN), respectively; then we screened key regulatory targets mainly distributing in lipid metabolism (PCK1, APOA4, APOA1, INHBE) and apoptosis (KIT, NTRK2) together with MAPK and PPAR signaling pathway in FLHS. Intriguingly, PCK1 was also significantly covered in up-regulated super-enhancers (SEs), which further implied the vital role of PCK1 during the development of FLHS. CONCLUSION: Together, our studies have identified potential therapeutic biomarkers of PCK1 and elucidated novel insights into the pathogenesis of FLHS, especially for the epigenetic perspective.

7.
Opt Express ; 32(5): 7611-7621, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38439438

RESUMO

Cavity optomechanics is concerned with the interaction between optical cavities and mechanical resonators. Here, we present systematic research on the dynamic behaviors of cavity optomechanical systems incorporating the influence of thermal nonlinearity. A dimensionless theoretical model was established to describe the system and numerical simulations were performed to study the dynamic behaviors. We theoretically identify the staircase effect, which can abruptly alter the system parameters when adiabatically sweeping the pump laser frequency across the optical cavity resonance and driving the mechanical resonator into oscillation. Moreover, we found bistability effects in several detuning intervals when sweeping the laser forward and backward. Both effects are analyzed theoretically and the roots lie in the thermal instability between averaged cavity energy and laser detuning. Our study shows the dynamic behaviors in an optomechanical-thermal system and provides guidance in leveraging the systems for applications in optical frequency comb, phonon laser, etc.

8.
Lang Speech ; : 238309241230895, 2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38462718

RESUMO

Rhotic sounds are some of the most challenging sounds for L2 learners to acquire. This study investigates the production of English rhotic sounds by Mandarin-English bilinguals with two English proficiency levels. The production of the English /ɹ/ by 17 Mandarin-English bilinguals was examined with ultrasound imaging and compared with the production of native English speakers. The ultrasound data show that bilinguals can produce native-like bunched and retroflex gestures, but the distributional pattern of tongue shapes in various contexts differs from that of native speakers. Acoustically, the English /ɹ/ produced by bilinguals had a higher F3 and F3-F2, as well as some frication noise in prevocalic /ɹ/, features similar to the Mandarin /ɹ/. Mandarin-English bilinguals did produce language-specific phonetic realizations for the English and Mandarin /ɹ/s. There was a positive correlation between language proficiency and English-specific characteristics of /ɹ/ by Mandarin-English bilinguals in both articulation and acoustics. Phonetic similarities facilitated rather than hindered L2 speech learning in production: Mandarin-English bilinguals showed better performance in producing the English /ɹ/ allophones that were more similar to the Mandarin /ɹ/ (syllabic and postvocalic /ɹ/s) than producing the English /ɹ/ allophone that was less similar to the Mandarin /ɹ/ (prevocalic /ɹ/). This study contributes to our understanding of the mechanism of speech production in late bilinguals.

9.
Mol Biol Rep ; 51(1): 229, 2024 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-38281249

RESUMO

BACKGROUND: Cancer is still a leading cause of mortality. Over the years, cancer therapy has undergone significant advances driven by advancements in science and technology. A promising area of drug discovery in this field involves the development of therapeutic targets for cancer treatment. The urgent need to identify new pharmacological targets arises from the impact of tumor resistance on the effectiveness of current medications. Specifically, the RPS6KB2 gene on chromosome 11 has been implicated in cell cycle regulation and exhibits higher expression levels in tumor tissue. Given this association, there is a potential for this gene to serve as a target for cancer treatment. METHODS: We conducted an analysis using the GTEx, TCGA, and CCLE databases to explore the relationship between RPS6KB2 and immune infiltration, the tumor microenvironment (TME), microsatellite instability (MSI), and more. Cell proliferation was assessed using EDU detection, while cell invasion and migration were evaluated via wound healing and Transwell assays. Additionally, western blot analysis was employed to measure expression of Bax, Bcl-2, MMP2, MMP9, PCNA, and proinflammatory factors. RESULTS: Through data analysis and molecular biology methods, our study carefully examined the potential role of RPS6KB2 in cancer therapy. The data revealed that RPS6KB2 is aberrantly expressed in most cancers and is associated with poor prognosis. Further analysis indicated its involvement in cancer cell apoptosis and migration, as well as its role in cancer immune processes. We validated the significance of RPS6KB2 in hepatocellular carcinoma (HCC), highlighting its capacity to upregulate proinflammatory cytokines. CONCLUSION: Our research indicates that RPS6KB2 is a prognostic biomarker associated with immune infiltration in cancer that can affect antitumor immunity by increasing secretion of proinflammatory factors, providing a potential drug target for cancer treatment.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Proteínas Quinases S6 Ribossômicas 90-kDa , Humanos , Citocinas/genética , Imunoterapia , Microambiente Tumoral/genética
10.
Int J Surg ; 110(4): 2366-2380, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38260944

RESUMO

BACKGROUND: Robot-assisted laparoscopic cystectomy with intracorporeal urinary diversion (iRARC) is increasingly being used in recent years. Whether iRARC offers advantages over open radical cystectomy (ORC) remains controversial. This study aimed to compare the difference of perioperative outcomes, oncological outcomes and complications between iRARC and ORC. METHODS: The PubMed, Embase, Cochrane Library, Web of Science and CNKI databases were searched in July 2023 according to the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) statement. Studies were identified to be eligible if they compared perioperative outcomes, oncological outcomes and complications in patients who underwent iRARC with ORC. RESULTS: Twenty-two studies involving 7020 patients were included. Compared to ORC, iRARC was superior for estimated blood loss [estimated blood loss (EBL) weighted mean difference (WMD): -555.52; 95% CI, -681.64 to -429.39; P <0.001], blood transfusion rate [odds ratio (OR): 0.16; 95% CI, 0.09-0.28; P <0.001], length of hospital stay [length of hospital stay (LOS) WMD: -2.05; 95% CI, -2.93 to -1.17; P <0.001], Clavien-Dindo grades ≥III complication rate [30 days: OR: 0.57; 95% CI 0.44-0.75; P <0.001; 90 days: OR: 0.71; 95% CI 0.60-0.84; P <0.001], and positive surgical margin [positive surgical margin (PSM) OR: 0.65; 95% CI 0.49-0.85; P =0.002]. However, iRARC had a longer operative time [operative time (OT) WMD: 68.54; 95% CI 47.41-89.67; P <0.001] and a higher rate of ureteroenteric stricture [ureteroenteric stricture (UES) OR: 1.56; 95% CI 1.16-2.11; P =0.003]. Time to flatus, time to bowel, time to regular diet, readmission rate, Clavien-Dindo grades less than III complication rate for iRARC were similar to that for ORC. Interestingly, the results of subgroup analysis revealed no difference in EBL between iRARC and ORC when the diversion type was neobladder. When the ileal conduit was selected as the diversion type, the LOS was similar in both procedures. CONCLUSION: Robot-assisted laparoscopic cystectomy with intracorporeal urinary diversion appears to be superior to open radical cystectomy in terms of effectiveness and safety. However, attention should be paid to the occurrence of ureteroenteric stricture during follow-up.


Assuntos
Cistectomia , Complicações Pós-Operatórias , Procedimentos Cirúrgicos Robóticos , Neoplasias da Bexiga Urinária , Derivação Urinária , Humanos , Cistectomia/métodos , Cistectomia/efeitos adversos , Derivação Urinária/métodos , Derivação Urinária/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Neoplasias da Bexiga Urinária/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Resultado do Tratamento , Tempo de Internação/estatística & dados numéricos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Duração da Cirurgia
11.
Pharmacol Ther ; 253: 108576, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38065232

RESUMO

RNA ac4C modification is a novel and rare chemical modification observed in mRNA. Traditional biochemical studies had primarily associated ac4C modification with tRNA and rRNA until in 2018, Arango D et al. first reported the presence of ac4C modification on mRNA and demonstrated its critical role in mRNA stability and translation regulation. Furthermore, they established that the ac4C modification on mRNA is mediated by the classical N-acetyltransferase NAT10. Subsequent studies have underscored the essential implications of NAT10 and mRNA ac4C modification across both physiological and pathological regulatory processes. In this review, we aimed to explore the discovery history of RNA ac4C modification, its detection methods, and its regulatory mechanisms in disease and physiological development. We offer a forward-looking examination and discourse concerning the employment of RNA ac4C modification as a prospective therapeutic strategy across diverse diseases. Furthermore, we comprehensively summarize the functions and mechanisms of NAT10 in gene expression regulation and pathogenesis independent of RNA ac4C modification.


Assuntos
Mamíferos , Acetiltransferases N-Terminal , Animais , Humanos , RNA Mensageiro , Mamíferos/genética
12.
Plant Cell Environ ; 47(2): 574-584, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37876357

RESUMO

The plasticity and growth of plant cell walls (CWs) remain poorly understood at the molecular level. In this work, we used atomic force microscopy (AFM) to observe elastic responses of the root transition zone of 4-day-old Arabidopsis thaliana wild-type and almt1-mutant seedlings grown under Fe or Al stresses. Elastic parameters were deduced from force-distance curve measurements using the trimechanic-3PCS framework. The presence of single metal species Fe2+ or Al3+ at 10 µM exerts no noticeable effect on the root growth compared with the control conditions. On the contrary, a mix of both the metal ions produced a strong root-extension arrest concomitant with significant increase of CW stiffness. Raising the concentration of either Fe2+ or Al3+ to 20 µM, no root-extension arrest was observed; nevertheless, an increase in root stiffness occurred. In the presence of both the metal ions at 10 µM, root-extension arrest was not observed in the almt1 mutant, which substantially abolishes the ability to exude malate. Our results indicate that the combination of Fe2+ and Al3+ with exuded malate is crucial for both CW stiffening and root-extension arrest. However, stiffness increase induced by single Fe2+ or Al3+ is not sufficient for arresting root growth in our experimental conditions.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Proteínas de Arabidopsis/genética , Malatos , Raízes de Plantas , Alumínio/farmacologia , Parede Celular , Íons
13.
Zool Res ; 45(1): 79-94, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38114435

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is associated with mutations in lipopolysaccharide-binding protein ( LBP), but the underlying epigenetic mechanisms remain understudied. Herein, LBP -/- rats with NAFLD were established and used to conduct integrative targeting-active enhancer histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation coupled with high-throughput and transcriptomic sequencing analysis to explore the potential epigenetic pathomechanisms of active enhancers of NAFLD exacerbation upon LBP deficiency. Notably, LBP -/- reduced the inflammatory response but markedly aggravated high-fat diet (HFD)-induced NAFLD in rats, with pronounced alterations in the histone acetylome and regulatory transcriptome. In total, 1 128 differential enhancer-target genes significantly enriched in cholesterol and fatty acid metabolism were identified between wild-type (WT) and LBP -/- NAFLD rats. Based on integrative analysis, CCAAT/enhancer-binding protein ß (C/EBPß) was identified as a pivotal transcription factor (TF) and contributor to dysregulated histone acetylome H3K27ac, and the lipid metabolism gene SCD was identified as a downstream effector exacerbating NAFLD. This study not only broadens our understanding of the essential role of LBP in the pathogenesis of NAFLD from an epigenetics perspective but also identifies key TF C/EBPß and functional gene SCD as potential regulators and therapeutic targets.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Animais , Ratos , Acetilação , Histonas/metabolismo , Lipídeos , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/veterinária , Estearoil-CoA Dessaturase/metabolismo
14.
Opt Express ; 31(24): 40261-40269, 2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-38041331

RESUMO

Amplified spontaneous emission (ASE) light is a common noise in optical communication systems with optical amplification, and a suitable optical carrier for optical covert communication. To deeply covert the secure signal, an in-band subnoise optical covert communication scheme is proposed and demonstrated by a proof-of-concept experiment. The power spectral density of optical secure channel is 10 dB less than the optical noise in the public channel. The covert signal is hidden in both optical and electrical domain, and can be transmitted with error-free. The trade-off between covertness and availability is discussed.

15.
Hum Genomics ; 17(1): 100, 2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-37957681

RESUMO

BACKGROUND: Accumulating observational studies have identified associations between type 1 diabetes (T1D) and polycystic ovary syndrome (PCOS). Still, the evidence about the causal effect of this association is uncertain. METHODS: We performed a two-sample Mendelian randomization (MR) analysis to test for the causal association between T1D and PCOS using data from a large-scale biopsy-confirmed genome-wide association study (GWAS) in European ancestries. We innovatively divided T1D into nine subgroups to be analyzed separately, including: type1 diabetes wide definition, type1 diabetes early onset, type 1 diabetes with coma, type 1 diabetes with ketoacidosis, type 1 diabetes with neurological complications, type 1 diabetes with ophthalmic complications, type 1 diabetes with peripheral circulatory complications, type 1 diabetes with renal complications, and type 1 diabetes with other specified/multiple/unspecified complications. GWAS data for PCOS were obtained from a large-scale GWAS (10,074 cases and 103,164 controls) for primary analysis and the IEU consortium for replication and meta-analysis. Sensitivity analyses were conducted to evaluate heterogeneity and pleiotropy. RESULTS: Following rigorous instrument selection steps, the number of SNPs finally used for T1D nine subgroups varying from 6 to 36 was retained in MR estimation. However, we did not observe evidence of causal association between type 1 diabetes nine subgroups and PCOS using the IVW analysis, MR-Egger regression, and weighted median approaches, and all P values were > 0.05 with ORs near 1. Subsequent replicates and meta-analyses also yielded consistent results. A number of sensitivity analyses also did not reveal heterogeneity and pleiotropy, including Cochran's Q test, MR-Egger intercept test, MR-PRESSO global test, leave-one-out analysis, and funnel plot analysis. CONCLUSION: This is the first MR study to investigate the causal relationship between type 1 diabetes and PCOS. Our findings failed to find substantial causal effect of type 1 diabetes on risk of PCOS. Further randomized controlled studies and MR studies are necessary.


Assuntos
Diabetes Mellitus Tipo 1 , Síndrome do Ovário Policístico , Feminino , Humanos , Biópsia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/genética , Olho , Estudo de Associação Genômica Ampla , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/genética , Análise da Randomização Mendeliana
16.
MedComm (2020) ; 4(5): e396, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37817894

RESUMO

Polycystic ovary syndrome (PCOS) is a prevalent reproductive endocrine disorder, with metabolic abnormalities and ovulation disorders. The post-translational modifications (PTMs) are functionally relevant and strengthen the link between metabolism and cellular functions. Lysine crotonylation is a newly identified PTM, the function of which in PCOS has not yet been reported. To explore the molecular mechanisms of crotonylation involved in the abnormalities of metabolic homeostasis and oocyte maturation in PCOS, by using liquid chromatography-tandem mass spectrometry analysis, we constructed a comprehensive map of crotonylation modifications in ovarian tissue of PCOS-like mouse model established by dehydroepiandrosterone induction. The crotonylation levels of proteins involved in metabolic processes were significantly decreased in PCOS ovaries compared to control samples. Further investigation showed that decrotonylation of Lon protease 1 (LONP1) at lysine 390 was associated with mitochondrial dysfunction in PCOS. Moreover, LONP1 crotonylation levels in PCOS were correlated with ovarian tissue oxidative stress levels, androgen levels, and oocyte development. Consistently, down-regulation of LONP1 and LONP1 crotonylation levels were also observed in the blood samples of PCOS patients. Collectively, our study revealed a mechanism by which the decrotonylation of LONP1 may attenuate its activity and alter follicular microenvironment to affect oocyte maturation in PCOS.

17.
J Org Chem ; 88(17): 12183-12193, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37579502

RESUMO

The photoswitching behaviors of heteroaryl azos and azobenzenes have attracted considerable interest due to their applications from material science to pharmacology. However, the use of UV light limits their application, especially in biomedicine and photopharmacology. In this work, using several aromaticity descriptors, including anisotropy of the induced current density analysis and nucleus-independent chemical shifts, we systematically investigate the relationship between anti-aromaticity and the absorption of a series of heterocyclic azos. We have demonstrated that the antiaromatic heterocycles substituted with diazenes enable the significant red shifts of the n → π* and π → π* transition bands of E and Z isomers via density functional theory calculations. Moreover, introducing substituents into heterocycles could further tune the absorption. Finally, the λmax of the first transition bands of the E (ca. 1026 nm) and Z isomers (ca. 1167 nm) of azos is achieved in the near-infrared region.

18.
J Mol Recognit ; 36(9): e3047, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37474122

RESUMO

Cry11Aa and Cyt1Aa are two pesticidal toxins produced by Bacillus thuringiensis subsp. israelensis. To improve our understanding of the nature of their oligomers in the toxic actions and synergistic effects, we performed the atomic force microscopy to probe the surfaces of their natively grown crystals, and used the L-weight filter to enhance the structural features. By L-weight filtering, molecular sizes of the Cry11Aa and Cyt1Aa monomers obtained are in excellent agreement with the three-dimensional structures determined by x-ray crystallography. Moreover, our results show that the layered feature of a structural element distinguishes the topographic characteristics of Cry11Aa and Cyt1Aa crystals, suggesting that the Cry11Aa toxin has a better chance than Cyt1Aa for multimerization and therefore cooperativeness of the toxic actions.


Assuntos
Bacillus thuringiensis , Endotoxinas , Endotoxinas/química , Endotoxinas/toxicidade , Toxinas de Bacillus thuringiensis , Proteínas Hemolisinas/química , Proteínas Hemolisinas/toxicidade , Proteínas de Bactérias/química , Bacillus thuringiensis/química
19.
World J Diabetes ; 14(6): 820-845, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37383594

RESUMO

BACKGROUND: The endoplasmic reticulum (ER) is closely related to a wide range of cellular functions and is a key component to maintain and restore metabolic health. Type 2 diabetes mellitus (T2DM) is a serious threat to human health, but the ER stress (ERS)-related mechanisms in T2DM have not been fully elucidated. AIM: To identify potential ERS-related mechanisms and crucial biomarkers in T2DM. METHODS: We conducted gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) in myoblast and myotube form GSE166502, and obtained the differentially expressed genes (DEGs). After intersecting with ERS-related genes, we obtained ERS-related DEGs. Finally, functional analyses, immune infiltration, and several networks were established. RESULTS: Through GSEA and GSVA, we identified several metabolic and immune-related pathways. We obtained 227 ERS-related DEGs and constructed several important networks that help to understand the mechanisms and treatment of T2DM. Finally, memory CD4+ T cells accounted for the largest proportion of immune cells. CONCLUSION: This study revealed ERS-related mechanisms in T2DM, which might contribute to new ideas and insights into the mechanisms and treatment of T2DM.

20.
Analyst ; 148(13): 2965-2974, 2023 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-37265393

RESUMO

A wearable sweat sensor, which could continuously monitor biomolecules related to the human physiological state, is emerging as a promising piece of health surveillance equipment. However, current sensors cannot simultaneously achieve a detection performance that equates to that of traditional sensors and satisfactory mechanical strength. Herein, a wearable sweat sensor with excellent detection performance and mechanical stability is designed and fabricated. Based on the integration of laser-induced graphene electrodes and a screen printing technique, this wearable sweat sensor could realize both the separate and simultaneous detection of uric acid (UA), tyrosine (Tyr), and ascorbic acid (AA) with high sensitivity. Good UA sensing performance in artificial sweat could be maintained even after 20 000 bends. In addition, the sensor can operate well in the wearing state or in a complex bovine whole blood sample. For the detection of human sweat, the changes in UA concentration after a purine-rich meal are continuously monitored and the results are in accordance with the corresponding serum UA detection results tested with a commercial serum UA meter. These results suggest its application potential in health monitoring for both gout patients and healthy humans.


Assuntos
Suor , Animais , Bovinos , Suor/química , Ácido Úrico/análise , Tirosina/análise , Ácido Ascórbico/análise , Humanos , Dispositivos Eletrônicos Vestíveis
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