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1.
Front Pharmacol ; 15: 1339758, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38948458

RESUMO

Background: The escalation of global population aging has accentuated the prominence of senile diabetes mellitus (SDM) as a consequential public health concern. Oxidative stress and chronic inflammatory cascades prevalent in individuals with senile diabetes significantly amplify disease progression and complication rates. Traditional Chinese Medicine (TCM) emerges as a pivotal player in enhancing blood sugar homeostasis and retarding complication onset in the clinical management of senile diabetes. Nonetheless, an evident research gap persists regarding the integration of TCM's renal tonification pharmacological mechanisms with experimental validation within the realm of senile diabetes therapeutics. Aims: The objective of this study was to investigate the mechanisms of action of New Shenqi Pills (SQP) in the treatment of SDM and make an experimental assessment. Methods: Network analysis is used to evaluate target pathways related to SQP and SDM. Mitochondrial-related genes were obtained from the MitoCarta3.0 database and intersected with the common target genes of the disease and drugs, then constructing a protein-protein interaction (PPI) network making use of the GeneMANIA database. Representative compounds in the SQP were quantitatively measured using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to ensure quality control and quantitative analysis of the compounds. A type 2 diabetes mice (C57BL/6) model was used to investigate the pharmacodynamics of SQP. The glucose lowering efficacy of SQP was assessed through various metrics including body weight and fasting blood glucose (FBG). To elucidate the modulatory effects of SQP on pancreatic beta cell function, we measured oral glucose tolerance test (OGTT), insulin histochemical staining and tunel apoptosis detection, then assessed the insulin-mediated phosphoinositide 3-kinase (PI3K)/protein kinase A (Akt)/glycogen synthase kinase-3ß (GSK-3ß) pathway in diabetic mice via Western blotting. Additionally, we observe the structural changes of the nucleus, cytoplasmic granules and mitochondria of pancreatic islet ß cells. Results: In this investigation, we identified a total of 1876 genes associated with senile diabetes, 278 targets of SQP, and 166 overlapping target genes, primarily enriched in pathways pertinent to oxidative stress response, peptide response, and oxygen level modulation. Moreover, an intersection analysis involving 1,136 human mitochondrial genes and comorbidity targets yielded 15 mitochondria-related therapeutic targets. Quality control assessments and quantitative analyses of SQP revealed the predominant presence of five compounds with elevated concentrations: Catalpol, Cinnamon Aldehyde, Rehmanthin D, Trigonelline, and Paeonol Phenol. Vivo experiments demonstrated notable findings. Relative to the control group, mice in the model group exhibited significant increases in body weight and fasting blood glucose levels, alongside decreased insulin secretion and heightened islet cell apoptosis. Moreover, ß-cells nuclear condensation and mitochondrial cristae disappearance were observed, accompanied by reduced expression levels of p-GSK-3ß protein in islet cells (p < 0.05 or p < 0.01). Conversely, treatment groups administered SQP and Rg displayed augmented expressions of the aforementioned protein markers (p < 0.05 or p < 0.01), alongside preserved mitochondrial cristae structure in islet ß cells. Conclusion: Our findings suggest that SQP can ameliorate diabetes by reducing islet cell apoptosis and resist oxidative stress. These insulin-mediated PI3K/AKT/GSK-3ß pathway plays an important regulatory role in this process.

2.
Front Psychol ; 15: 1365817, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38952833

RESUMO

Background: Meaning in life is a crucial aspect of psychological well-being, often overlooked despite its clinical significance. This warrants further investigation, especially regarding its relationship with frailty and psychological resilience. Objective: This study aims to assess the status and relevance of frailty, psychological resilience, and meaning in life among older adults in Chinese nursing homes. Additionally, it explores the mediating role of psychological resilience between frailty and meaning in life, providing insights to improve the meaning in life for older adults in nursing homes. Methods: Between August 2022 and November 2022, 302 older adults in Chinese nursing homes were selected using convenience sampling. The study utilized the Socio-demographic Characteristics Questionnaire, Tilburg Frailty Indicator, Connor-Davidson Resilience Scale, and the Source of Meaning Scale for Older Adults. A face-to-face questionnaire survey was conducted, and SPSS 27.0 was employed for analyzing correlations between frailty, psychological resilience, and meaning in life. The mediating effect of psychological resilience was assessed using Model 4 in the Process plug-in. Results: Older adults in nursing homes exhibited a frailty total score of 4.00 (2.00, 5.00), with a prevalence of 28.5%. Psychological resilience scored 66.00 (51.75, 76.00), and meaning in life scored 149.00 (132.00, 158.25). Frailty showed a negative correlation with both meaning in life and psychological resilience, while meaning in life demonstrated a positive correlation with psychological resilience. Psychological resilience exhibited a partial mediating effect, accounting for 51.04% of the total effect between frailty and meaning in life. Conclusion: Frailty incidence is high among older adults in nursing homes, with psychological resilience at a general level and meaning in life in the upper middle level. Psychological resilience plays a crucial role as a partial mediator between frailty and meaning in life. Timely assessment of frailty, targeted interventions, and improvements in psychological resilience are essential for enhancing the meaning in life and promoting successful aging.

3.
Cardiovasc Diabetol ; 23(1): 226, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38951808

RESUMO

BACKGROUND: The atherogenic index of plasma (AIP) is closely associated with the onset of diabetes, with obesity being a significant risk factor for type 2 diabetes mellitus (T2DM). However, the association between the AIP and T2DM in overweight and obese populations has been infrequently studied. Therefore, this study aimed to explore this association in overweight and obese individuals with T2DM. METHODS: This cross-sectional analysis utilized data from 40,633 participants with a body mass index (BMI) ≥ 24 kg/m2 who were screened from January 2018 to December 2023 at Henan Provincial People's Hospital. Participants were categorized into groups of overweight and obese individuals with and without diabetes according to the T2DM criteria. The AIP, our dependent variable, was calculated using the formula log10 [(TG mol/L)/HDL-C (mol/L)]. We investigated the association between the AIP and T2DM in overweight and obese individuals using multivariate logistic regression, subgroup analysis, generalized additive models, smoothed curve fitting, and threshold effect analysis. Additionally, mediation analysis evaluated the role of inflammatory cells in AIP-related T2DM. RESULTS: Overweight and obese patients with T2DM exhibited higher AIP levels than those without diabetes. After adjusting for confounders, our results indicated a significant association between the AIP and the risk of T2DM in overweight and obese individuals (odds ratio (OR) = 5.17, 95% confidence interval (CI) 4.69-5.69). Notably, participants with a high baseline AIP (Q4 group) had a significantly greater risk of T2DM than those in the Q1 group, with an OR of 3.18 (95% CI 2.94-3.45). Subgroup analysis revealed that the association between the AIP and T2DM decreased with increasing age (interaction P < 0.001). In overweight and obese populations, the association between AIP and T2DM risk displayed a J-shaped nonlinear pattern, with AIP > - 0.07 indicating a significant increase in T2DM risk. Various inflammatory cells, including neutrophils, leukocytes, and monocytes, mediated 4.66%, 4.16%, and 1.93% of the associations, respectively. CONCLUSION: In overweight and obese individuals, the AIP was independently associated with T2DM, exhibiting a nonlinear association. Additionally, the association between the AIP and T2DM decreased with advancing age. Multiple types of inflammatory cells mediate this association.


Assuntos
Biomarcadores , Diabetes Mellitus Tipo 2 , Obesidade , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Aterosclerose/epidemiologia , Aterosclerose/sangue , Aterosclerose/diagnóstico , Biomarcadores/sangue , Índice de Massa Corporal , China/epidemiologia , HDL-Colesterol/sangue , Estudos Transversais , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , População do Leste Asiático , Obesidade/diagnóstico , Obesidade/sangue , Obesidade/epidemiologia , Sobrepeso/epidemiologia , Sobrepeso/sangue , Sobrepeso/diagnóstico , Sobrepeso/complicações , Prognóstico , Medição de Risco , Fatores de Risco , Triglicerídeos/sangue
4.
Adv Sci (Weinh) ; : e2401869, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38959395

RESUMO

Ionic conductive hydrogels (ICHs) have recently gained prominence in biosensing, indicating their potential to redefine future biomedical applications. However, the integration of these hydrogels into sensor technologies and their long-term efficacy in practical applications pose substantial challenges, including a synergy of features, such as mechanical adaptability, conductive sensitivity, self-adhesion, self-regeneration, and microbial resistance. To address these challenges, this study introduces a novel hydrogel system using an imidazolium salt with a ureido backbone (UL) as the primary monomer. Fabricated via a straightforward one-pot copolymerization process that includes betaine sulfonate methacrylate (SBMA) and acrylamide (AM), the hydrogel demonstrates multifunctional properties. The innovation of this hydrogel is attributed to its robust mechanical attributes, outstanding strain responsiveness, effective water retention, and advanced self-regenerative and healing capabilities, which collectively lead to its superior performance in various applications. Moreover, this hydrogel  exhibited broad-spectrum antibacterial activity. Its potential for biomechanical monitoring, especially in tandem with contact and noncontact electrocardiogram (ECG) devices, represents a noteworthy advancement in precise real-time cardiac monitoring in clinical environments. In addition, the conductive properties of the hydrogel make it an ideal substrate for electrophoretic patches aimed at treating infected wounds and consequently enhancing the healing process.

5.
Adv Biol (Weinh) ; : e2400224, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38963310

RESUMO

The maintenance and expansion of human neural stem cells (hNSCs) in 3D tissue scaffolds is a promising strategy in producing cost-effective hNSCs with quality and quantity applicable for clinical applications. A few biopolymers have been extensively used to fabricate 3D scaffolds, including hyaluronic acid, collagen, alginate, and chitosan, due to their bioactive nature and availability. However, these polymers are usually applied in combination with other biomolecules, leading to their responses difficult to ascribe to. Here, scaffolds made of chitosan, alginate, hyaluronic acid, or collagen, are explored for hNSC expansion under xeno-free and chemically defined conditions and compared for hNSC multipotency maintenance. This study shows that the scaffolds made of pure chitosan support the highest adhesion and growth of hNSCs, yielding the most viable cells with NSC marker protein expression. In contrast, the presence of alginate, hyaluronic acid, or collagen induces differentiation toward immature neurons and astrocytes even in the maintenance medium and absence of differentiation factors. The cells in pure chitosan scaffolds preserve the level of transmembrane protein profile similar to that of standard culture. These findings point to the potential of using pure chitosan scaffolds as a base scaffolding material for hNSC expansion in 3D.

6.
Front Oncol ; 14: 1288041, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38962263

RESUMO

Background: Small Bowel Adenocarcinoma (SBA) is rare, occult and life-threatening malignancy in digestive system. Given low incidence and nonspecific symptoms, SBA is frequently detected in later stages. Double contrast enhanced ultrasound (DCEUS) is an innovative imaging technique applied to visualize the gastrointestinal tract, merging intravenous contrast-enhanced ultrasound with oral contrast-enhanced ultrasound. In this case, DCEUS was utilized and successfully detected an SBA of the jejunum. Case presentation: A Chinese woman, aged 64, sought consultation in the gastroenterology department at our hospital, reporting symptoms of abdominal pain. Three months before entering the hospital, she underwent gastroscopy and colonoscopy which suggested chronic gastritis, and she was treated with oral drugs. However, her symptoms were not relieved, and even worsened. To further investigate, DCEUS was performed. The oral contrast agent dilated the luminal space of the upper gastrointestinal tract, resolving the hindrance caused by gas in the gastrointestinal tract and creating an acoustic window for scanning. Through this acoustic window, oral agent contrast-enhanced ultrasound (OA-CEUS) revealed a localized thickening of jejunal intestinal wall measuring 4x3 cm. Following intravenous injection of ultrasound contrast agent, the jejunal lesion exhibited faster enhancement and heterogeneous hyper-enhancement. Finally, the patient underwent jejunal tumor resection. Pathological examination revealed a jejunal adenocarcinoma. Conclusion: The timely diagnosis of SBA can be challenging. DCEUS may have the potential to contribute to diagnosis and detailed evaluation of SBA, particularly in cases involving jejunum. Further researches are needed to fully explore the benefits of DCEUS in the standard diagnostic approach for small bowel diseases.

7.
Balkan Med J ; 41(4): 286-297, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38966918

RESUMO

Background: Cannabidiol (CBD), extracted from Cannabis sativa, has anticancer, anti-inflammation, and analgesic effects. Nevertheless, its therapeutic effect and the mechanism by which it alleviates oral mucositis (OM) remain unclear. Aims: To explore the impact of CBD on OM in mice and on human oral keratinocyte (HOK) cells. Study Design: Expiremental study. Methods: The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, GeneCard, DisGeNET, and Gene Expression Omnibus databases were used to conduct therapeutic target gene screening for drugs against OM. Cytoscape software was used to build networks linking components, targets, and diseases. The STRING database facilitated analysis of intertarget action relationships, and the target genes were analyzed for Kyoto Encyclopedia of Genes and Genomes pathway enrichment. Occurrence of serum inflammation-related factors, hematoxylin and eosin staining, and immunohistochemistry were used to assess OM injury. Cell proliferation, migration, pyroptosis, and apoptosis of HOK cells under different treatments were assessed. Molecular mechanisms were elucidated through western blot and quantitative real-time polymerase chain reaction analyses. Results: A total of 49 overlapping genes were pinpointed as potential targets, with NF-κB1, PIK3R1, NF-κBIA, and AKT1 being recognized as hub genes among them. Additionally, the PI3K/Akt/NF-κB and interleukin-17 signaling pathways were identified as relevant. Our in vivo experiments showed that CBD significantly reduced the proportion of lesion area, mitigated oral mucosal tissue lesions, and downregulated the expression levels of genes and levels of proteins, including NLRP3, P65, AKT, and PI3K. In vitro experiments indicated that CBD enhanced HOK cell proliferation and migration and reduced apoptosis through inhibition of the PI3K/Akt/NF-κB signaling pathway and pyroptosis. Conclusion: Our findings suggest a novel mechanism for controlling OM, in which CBD suppresses the PI3K/Akt/NF-κB signaling pathway and pyroptosis, thereby mitigating OM symptoms.


Assuntos
Canabidiol , NF-kappa B , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Piroptose , Estomatite , Canabidiol/farmacologia , Canabidiol/uso terapêutico , Animais , Piroptose/efeitos dos fármacos , Camundongos , Estomatite/tratamento farmacológico , NF-kappa B/efeitos dos fármacos , NF-kappa B/análise , Fosfatidilinositol 3-Quinases/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Humanos , Transdução de Sinais/efeitos dos fármacos , Modelos Animais de Doenças
8.
Rev Sci Instrum ; 95(7)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38949472

RESUMO

With the development of 5G technology, the accurate measurement of the complex permittivity of a printed circuit board (PCB) in the wide frequency range is crucial for the design of high-frequency circuits. In this paper, a microwave measurement device and method based on the double-sided parallel-strip line (DSPSL) resonator have been developed to measure the complex permittivity of typical PCBs in the vertical direction. The device includes the DSPSL resonator, the DSPSL coupling probe, a pressure monitor, a Farran C4209 vector network analyzer (100 K to 9 GHz), and a FEV-10-PR-0006 frequency multiplier (75-110 GHz). Based on transmission line theory, the physical model of the DSPSL resonator was established, and the relative permittivity and loss angle tangent value of the dielectric substrate were calculated using conformal transformation. To excite the resonator, the DSPSL coupling probe with a good transmission effect was designed, which consists of DSPSL microstrip line (MSL) transition structure and an MSL-WR10 rectangular waveguide converter. To reduce the air gap between the sample and the metal guide band and dielectric support block, and to improve test accuracy, a mechanical pressure device is added to the top of the DSPSL resonator. Based on the DSPSL resonator, we have used the device to test four typical PCBs, namely, polytetrafluoroethylene, Rogers RT/duroid®5880, Rogers RO3006®, and Rogers RO3010®. The results show that the maximum error of the relative permittivity is less than 3.05%, and the maximum error of the loss angle tangent is less than 1.27 × 10-4.

9.
Sci Data ; 11(1): 762, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38992134

RESUMO

Advancements in sequencing have enabled the assembly of numerous sheep genomes, significantly advancing our understanding of the link between genetic variation and phenotypic traits. However, the genome of East Friesian sheep (Ostfriesisches Milchschaf), a key high-yield milk breed, remains to be fully assembled. Here, we constructed a near-complete and gap-free East Friesian genome assembly using PacBio HiFi, ultra-long ONT and Hi-C sequencing. The resulting genome assembly spans approximately 2.96 Gb, with a contig N50 length of 104.1 Mb and only 164 unplaced sequences. Remarkably, our assembly has captured 41 telomeres and 24 centromeres. The assembled sequence is of high quality on completeness (BUSCO score: 97.1%) and correctness (QV: 69.1). In addition, a total of 24,580 protein-coding genes were predicted, of which 97.2% (23,891) carried at least one conserved functional domain. Collectively, this assembly provides not only a near T2T gap-free genome, but also provides a valuable genetic resource for comparative genome studies of sheep and will serve as an important tool for the sheep research community.


Assuntos
Genoma , Animais , Análise de Sequência de DNA , Ovinos/genética , Telômero/genética
10.
Nat Commun ; 15(1): 5987, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39013913

RESUMO

Ethylene regulates plant growth, development, and stress adaptation. However, the early signaling events following ethylene perception, particularly in the regulation of ethylene receptor/CTRs (CONSTITUTIVE TRIPLE RESPONSE) complex, remains less understood. Here, utilizing the rapid phospho-shift of rice OsCTR2 in response to ethylene as a sensitive readout for signal activation, we revealed that MHZ3, previously identified as a stabilizer of ETHYLENE INSENSITIVE 2 (OsEIN2), is crucial for maintaining OsCTR2 phosphorylation. Genetically, both functional MHZ3 and ethylene receptors prove essential for OsCTR2 phosphorylation. MHZ3 physically interacts with both subfamily I and II ethylene receptors, e.g., OsERS2 and OsETR2 respectively, stabilizing their association with OsCTR2 and thereby maintaining OsCTR2 activity. Ethylene treatment disrupts the interactions within the protein complex MHZ3/receptors/OsCTR2, reducing OsCTR2 phosphorylation and initiating downstream signaling. Our study unveils the dual role of MHZ3 in fine-tuning ethylene signaling activation, providing insights into the initial stages of the ethylene signaling cascade.


Assuntos
Etilenos , Regulação da Expressão Gênica de Plantas , Oryza , Proteínas de Plantas , Receptores de Superfície Celular , Transdução de Sinais , Oryza/metabolismo , Oryza/genética , Etilenos/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Fosforilação , Receptores de Superfície Celular/metabolismo , Receptores de Superfície Celular/genética , Plantas Geneticamente Modificadas , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética
11.
Magn Reson Med ; 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39044635

RESUMO

PURPOSE: To develop a deep learning-based approach to reduce the scan time of multipool CEST MRI for Parkinson's disease (PD) while maintaining sufficient prediction accuracy. METHOD: A deep learning approach based on a modified one-dimensional U-Net, termed Z-spectral compressed sensing (CS), was proposed to recover dense Z-spectra from sparse ones. The neural network was trained using simulated Z-spectra generated by the Bloch equation with various parameter settings. Its feasibility and effectiveness were validated through numerical simulations and in vivo rat brain experiments, compared with commonly used linear, pchip, and Lorentzian interpolation methods. The proposed method was applied to detect metabolism-related changes in the 6-hydroxydopamine PD model with multipool CEST MRI, including APT, CEST@2 ppm, nuclear Overhauser enhancement, direct saturation, and magnetization transfer, and the prediction performance was evaluated by area under the curve. RESULTS: The numerical simulations and in vivo rat-brain experiments demonstrated that the proposed method could yield superior fidelity in retrieving dense Z-spectra compared with existing methods. Significant differences were observed in APT, CEST@2 ppm, nuclear Overhauser enhancement, and direct saturation between the striatum regions of wild-type and PD models, whereas magnetization transfer exhibited no significant difference. Receiver operating characteristic analysis demonstrated that multipool CEST achieved better predictive performance compared with individual pools. Combined with Z-spectral CS, the scan time of multipool CEST MRI can be reduced to 33% without distinctly compromising prediction accuracy. CONCLUSION: The integration of Z-spectral CS with multipool CEST MRI can enhance the prediction accuracy of PD and maintain the scan time within a reasonable range.

12.
Prog Biophys Mol Biol ; 191: 1-10, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38971324

RESUMO

Transfer RNA-derived small RNAs (tsRNAs), a recently identified subclass of small non-coding RNAs (sncRNAs), emerge through the cleavage of mature transfer RNA (tRNA) or tRNA precursors mediated by specific enzymes. The tumor necrosis factor (TNF) protein, a signaling molecule produced by activated macrophages, plays a pivotal role in systemic inflammation. Its multifaceted functions include the capacity to eliminate or hinder tumor cells, enhance the phagocytic capabilities of neutrophils, confer resistance against infections, induce fever, and prompt the production of acute phase proteins. Notably, four TNF-related tsRNAs have been conclusively linked to distinct diseases. Examples include 5'tiRNA-Gly in skeletal muscle injury, tsRNA-21109 in systemic lupus erythematosus (SLE), tRF-Leu-AAG-001 in endometriosis (EMs), and tsRNA-04002 in intervertebral disk degeneration (IDD). These tsRNAs exhibit the ability to suppress the expression of TNF-α. Additionally, KEGG analysis has identified seven tsRNAs potentially involved in modulating the TNF pathway, exerting their influence across a spectrum of non-cancerous diseases. Noteworthy instances include aberrant tiRNA-Ser-TGA-001 and tRF-Val-AAC-034 in intrauterine growth restriction (IUGR), irregular tRF-Ala-AGC-052 and tRF-Ala-TGC-027 in obesity, and deviant tiRNA-His-GTG-001, tRF-Ser-GCT-113, and tRF-Gln-TTG-035 in irritable bowel syndrome with diarrhea (IBS-D). This comprehensive review explores the biological functions and mechanisms of tsRNAs associated with the TNF signaling pathway in both cancer and other diseases, offering novel insights for future translational medical research.

13.
J R Stat Soc Series B Stat Methodol ; 86(3): 694-713, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39005888

RESUMO

Quantifying the association between components of multivariate random curves is of general interest and is a ubiquitous and basic problem that can be addressed with functional data analysis. An important application is the problem of assessing functional connectivity based on functional magnetic resonance imaging (fMRI), where one aims to determine the similarity of fMRI time courses that are recorded on anatomically separated brain regions. In the functional brain connectivity literature, the static temporal Pearson correlation has been the prevailing measure for functional connectivity. However, recent research has revealed temporally changing patterns of functional connectivity, leading to the study of dynamic functional connectivity. This motivates new similarity measures for pairs of random curves that reflect the dynamic features of functional similarity. Specifically, we introduce gradient synchronization measures in a general setting. These similarity measures are based on the concordance and discordance of the gradients between paired smooth random functions. Asymptotic normality of the proposed estimates is obtained under regularity conditions. We illustrate the proposed synchronization measures via simulations and an application to resting-state fMRI signals from the Alzheimer's Disease Neuroimaging Initiative and they are found to improve discrimination between subjects with different disease status.

14.
Anal Chem ; 96(29): 12006-12011, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-38993005

RESUMO

Monitoring the conformational dynamics of individual proteins is essential to understand the relationship between structure and function in molecular regulatory mechanisms. However, the fast dynamics of single proteins remain poorly understood. Here, we construct a single-molecule sensing platform by introducing plasmonic imaging of single nanoparticles to sense and report the protein conformational changes at the single-molecule level. Tracking the fluctuations of individual nanoparticles with high resolution, we detect and characterize distinct conformational states of molecular chaperone heat shock protein 90 (Hsp90). We also explore the conformational changes of Hsp90 in situ under different nucleotide conditions. Analysis of the conformational fluctuations between the open and closed states of single Hsp90 provides important information on free energy profiles, effective spring constants, and multiphase behaviors. This method offers a strategy to visualize the conformational changes of single proteins in real-time and provides insights into the underlying molecular mechanisms.


Assuntos
Proteínas de Choque Térmico HSP90 , Conformação Proteica , Proteínas de Choque Térmico HSP90/química , Proteínas de Choque Térmico HSP90/metabolismo , Termodinâmica , Imagem Individual de Molécula/métodos , Nanopartículas Metálicas/química
15.
Proc Natl Acad Sci U S A ; 121(29): e2401834121, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-38976739

RESUMO

Lung adenocarcinoma (LUAD) is the leading cause of cancer-related death worldwide, but the underlying molecular mechanisms remain largely unclear. The transcription factor (TF) specificity protein 1 (SP1) plays a crucial role in the development of various cancers, including LUAD. Recent studies have indicated that master TFs may form phase-separated macromolecular condensates to promote super-enhancer (SE) assembly and oncogene expression. In this study, we demonstrated that SP1 undergoes phase separation and that its zinc finger 3 in the DNA-binding domain is essential for this process. Through Cleavage Under Targets & Release Using Nuclease (CUT&RUN) using antibodies against SP1 and H3K27ac, we found a significant correlation between SP1 enrichment and SE elements, identified the regulator of the G protein signaling 20 (RGS20) gene as the most likely target regulated by SP1 through SE mechanisms, and verified this finding using different approaches. The oncogenic activity of SP1 relies on its phase separation ability and RGS20 gene activation, which can be abolished by glycogen synthase kinase J4 (GSK-J4), a demethylase inhibitor. Together, our findings provide evidence that SP1 regulates its target oncogene expression through phase separation and SE mechanisms, thereby promoting LUAD cell progression. This study also revealed an innovative target for LUAD therapies through intervening in SP1-mediated SE formation.


Assuntos
Adenocarcinoma de Pulmão , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares , Proteínas RGS , Fator de Transcrição Sp1 , Fator de Transcrição Sp1/metabolismo , Fator de Transcrição Sp1/genética , Humanos , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Proteínas RGS/metabolismo , Proteínas RGS/genética , Linhagem Celular Tumoral , Animais , Elementos Facilitadores Genéticos , Progressão da Doença , Camundongos , Separação de Fases
16.
Inorg Chem ; 63(29): 13755-13765, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-38982641

RESUMO

Developing high-performance electrodes for flexible antifreezing energy storage devices has been a significant challenge with the increasing demand for portable components. In this work, Cr-substituted SrCoO3-δ perovskites were first proposed as potential low-temperature supercapacitor electrode materials. The high-valence Cr6+ ([Ne]3s23p6) substitution favors a high-spin state of Co ions with enhanced electronic repulsion effect, ultimately forming a stable cubic structure with high conductivity. Accordingly, the modification strategies of SrCoO3 through the p6 configuration cation substitution have been improved. As a result, the asymmetric SrCo0.95Cr0.05O3-δ@CC//PPy@CC device exhibited a high energy density of 44.90 Wh kg-1 at 902.01 W kg-1 and maintained a 95.8% specific capacitance after 10,000 cycles, demonstrating an ultralong cyclic stability. The dramatically improved electrochemical performance was attributed to the stabilized crystal structure, increased oxygen vacancy, and accelerated oxygen diffusion rate. Furthermore, a quasi-solid-state supercapacitor with ethylene glycol (EG)-modified KOH/PVA organohydrogel electrolyte was developed through an advance in situ-integrated strategy. After bending at 180° for 1000 cycles, only a 9.7% capacity decay was observed. Even under -40 °C, the supercapacitor has a large energy density of 46.94 µWh cm-2. The present work represents the initial investigation into utilizing perovskite materials for antifreezing energy storage device, thereby confirming their potential application as low-temperature electronic components.

17.
Medicine (Baltimore) ; 103(29): e38965, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39029008

RESUMO

RATIONALE: Salivary duct carcinoma (SDC) is an aggressive form of cancer, with cutaneous metastasis being a rare occurrence. Furthermore, cutaneous metastasis of SDC secondary to a scald is even rarer, and to the best of our knowledge, our case represents the first such instance. Considering the involvement of the fingers in the metastatic site, which may affect limb function and quality of life, we present this case to explore the reason why scald could lead to distant recurrence and better treatment options. PATIENT CONCERNS: An 85-year-old man diagnosed with SDC in the parotid gland found enlarged masses at the fingertips as a consequence of a burn, 6 years after his initial treatment. DIAGNOSES: Cutaneous metastasis of SDC in the parotid gland and left thumb loss due to surgery. INTERVENTIONS: Radiotherapy was offered, targeting at the masses on the fingers, with dose at 15 Gy in 3 fractions, 12 Gy in 3 fractions, 15 Gy in 3 fractions for both hands and additional 21 Gy in 7 fractions only for left hand. OUTCOMES: The tumors shrank after 2 months of radiotherapy and the patient recovered well. Side effects included nail hyperplasia and paronychia. LESSONS: Connections between scald and distant metastasis of malignant tumors in this case needed further investigation. Considering reserving function of the fingers while dealing with metastasis, radiotherapy is recommended rather than surgery.


Assuntos
Dedos , Neoplasias Cutâneas , Idoso de 80 Anos ou mais , Humanos , Masculino , Carcinoma Ductal/secundário , Carcinoma Ductal/patologia , Carcinoma Ductal/terapia , Dedos/patologia , Neoplasias Parotídeas/patologia , Ductos Salivares/patologia , Neoplasias das Glândulas Salivares/patologia , Neoplasias Cutâneas/secundário , Neoplasias Cutâneas/patologia
18.
Ecotoxicol Environ Saf ; 282: 116710, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39024953

RESUMO

The adverse impacts of chronic hypoxia on maternal and infant health at high altitudes warrant significant attention. However, effective protective measures against the resultant growth restrictions and neurodevelopmental disorders in infants and young children are still lacking. This study investigated the neurodevelopment of mice offspring under hypoxic conditions by exposing pregnant mice to a hypobaric oxygen chamber that simulated the hypobaric hypoxia at an altitude of 4000 m until 28 days after delivery. Our findings suggested that prolonged exposure to hypoxia might result in emotional abnormalities and social disorders in offspring. The significant reduction in astrogliogenesis was a characteristic feature associated with neurodevelopmental disorders induced by hypoxia. Further studies demonstrated that cold-induced RNA-binding protein (CIRBP) was a key transcriptional regulator in astrogliogenesis, which downregulated astrocytic differentiation under hypoxia through its crosstalk with the NFIA. Our study emphasized the crucial role of CIRBP in regulating astrogliogenesis and highlighted its potential as a promising target for therapeutic interventions in neurodevelopmental disorders associated with hypoxia.

19.
Arch Biochem Biophys ; : 110102, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39029644

RESUMO

Abdominal aortic aneurysm (AAA) is a dangerous condition affecting the aorta. Macrophage pyroptosis, phenotypic transformation, and apoptosis of aortic smooth muscle cells (ASMCs) are pivotal mechanisms in AAA pathogenesis. This study explores how Gasdermin B (GSDMB) regulates macrophage non-canonical pyroptosis and its impact on the phenotypic transformation and apoptosis of ASMCs, thereby unveiling the role of GSDMB in AAA pathogenesis. Immunofluorescence analysis was used to assess the expression levels and localization of GSDMB, cysteinyl aspartate-specific protease-4 (Caspase-4), and N-terminal of cleaved GSDMD (N-GSDMD) in AAA tissues. A cell model that mimics macrophage non-canonical pyroptosis was established by treating THP-1 cells with lipopolysaccharide (LPS). THP-1 cells with reduced or increased GSDMB were generated using small interfering RNA (siRNA) or plasmids. Co-culture experiments involving THP-1 cells and HASMCs were conducted to explore the impact of GSDMB on HASMCs. The mitochondrial reactive oxygen species (mtROS) scavenger Mito-TEMPO lowered mtROS levels in THP-1 cells. Our findings revealed that GSDMB was significantly upregulated in AAA macrophages, which was accompanied by robust non-canonical pyroptosis. THP-1 cells showed non-canonical pyroptosis in response to LPS, which was accompanied by an increase in GSDMB. Further research demonstrated that altering GSDMB, either by knockdown or overexpression, can affect macrophage non-canonical pyroptosis as well as the phenotypic transformation and apoptosis of HASMCs. LPS-induced non-canonical pyroptosis in THP-1 cells was associated with an increase in mtROS, whereas Mito-TEMPO effectively decreased non-canonical pyroptosis and the expression of GSDMB. These findings suggest that GSDMB plays a role in AAA macrophage non-canonical pyroptosis, which influences the phenotypic transformation and apoptosis of HASMCs. The mtROS-Dynamin-Related Protein 1 (Drp1) axis is likely to regulate the GSDMB-mediated non-canonical pyroptosis.

20.
PLoS One ; 19(7): e0307510, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39028726

RESUMO

In this cross-sectional study of 1475 Chinese university students, we explored associated factors of attitude and willingness of biodiversity conservation, analyzed the hypothesized mediation by social support in the association between attitude and willingness of biodiversity conservation. Multivariate logistic regression model revealed that major and social support were prominently related to both attitude and willingness of biodiversity conservation. Besides, path model identified a statistically significant mediation by social support, sex, race, and family residence presented noticeable effect modification on the mediation of social support. These major findings suggest that intervention measures which aiming at enhancing social support could be considered for elevating attitude and willingness of biodiversity conservation among Chinese university students.


Assuntos
Atitude , Biodiversidade , Conservação dos Recursos Naturais , Apoio Social , Estudantes , Humanos , Masculino , Feminino , Estudantes/psicologia , Universidades , China , Adulto Jovem , Estudos Transversais , Adulto , Adolescente , Inquéritos e Questionários
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