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1.
Environ Sci Technol ; 58(43): 19362-19371, 2024 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-39431321

RESUMO

Chemical fingerprinting to characterize the occurrence state and abundance of organic and inorganic constituents within fine particulate matter (PM2.5) is useful in evaluating the associated health risks and tracing pollution sources. Herein, an analytical strategy for the rapid analysis of metal and organic constituents in PM2.5 was developed employing a combination of sequential chemical extraction coupled with mass spectrometry detection. H2O, CH3OH, EDTA-2Na, electrochemical oxidation, and electrochemical reduction were sequentially utilized to extract the chemical constituents in PM2.5 samples on a homemade device employing simultaneous online detection using two linear trap quadrupole mass spectrometers (LTQ-MS) with electrospray ionization (ESI) in positive and negative modes. After a single analytical procedure, dozens of metals (e.g., Pb, Cr, and Cu), organic compounds (e.g., amines, polycyclic aromatic hydrocarbons, and aliphatic acids), and negative ions (e.g., NO3-, NO2-, and Cl-) were comprehensively detected in the water-soluble, liposoluble, insoluble, oxidizable, and reducible fractions of PM2.5 samples, and their physical and chemical relationships were established.


Assuntos
Material Particulado , Espectrometria de Massas/métodos , Metais/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Poluentes Atmosféricos/análise
2.
Biochem Pharmacol ; 230(Pt 1): 116576, 2024 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-39424201

RESUMO

N6-methyladenosine (m6A) is a prevalent mRNA modification in eukaryotic cells, characterized by its reversible nature. YTH structural domain family protein 2 (YTHDF2), a key reader of m6A, plays a crucial role in identifying and binding m6A-containing RNAs, thereby influencing RNA metabolism through various functional mechanisms. The upstream and downstream targets of YTHDF2 are critical in the pathogenesis of various central nervous system (CNS) diseases, affecting disease development by regulating signaling pathways and gene expression. This paper provides an overview of current research on the role of YTHDF2 in CNS diseases and investigates the regulatory mechanisms by which YTHDF2 influences the development of these conditions. This exploration aims to improve understanding of disease pathogenesis and offer novel insights for the targeted prevention and treatment of neurological disorders.

3.
Cerebrovasc Dis ; : 1-18, 2024 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-39433033

RESUMO

INTRODUCTION: Accurately predicting a patient's prognosis is an important component of decision-making in intracerebral hemorrhage (ICH). We aimed to determine clinicians' ability to predict survival, functional recovery, and return to premorbid activities in patients with ICH. METHODS: Pre-specified secondary analysis of the third INTEnsive care bundle with blood pressure Reduction in Acute Cerebral hemorrhage Trial (INTERACT3), an international, multicenter, stepped-wedge cluster randomized controlled trial. Clinician perspectives on prognosis were collected at hospital admission and Day 7 (or before discharge). Prognosis questions were the likelihood of (i) survival at 48 hours and 6 months, (ii) favorable functional outcome (recovery walking and self-care) and (iii) return to usual activities at 6 months. Clinician predictions were compared with actual outcomes. RESULTS: Most clinician participants were from neurosurgery (75%) with a median of 8 working years (IQR 5-14) of experience. Of the 6305 randomized patients who survived 48 hours, 213 (3.4%) were predicted to die (positive predictive value [PPV] 0.99, 95% confidence interval [CI] 0.99-0.99). Of 5435 patients who survived 6 months, 209 (3.8%) were predicted to die (PPV 0.93, 95% CI 0.92-0.93). Predictions on favorable functional outcome (PPV 0.54, 95% CI 0.52-0.56) and satisfied ability to return to usual activities (PPV 0.50, 95% CI 0.49-0.52) were poor. Prediction accuracy varied by working years and region of practice. CONCLUSIONS: In patients with ICH, clinician estimates of death are very good but conversely they are poor in predicting higher levels of functional recovery and activities.

4.
Front Microbiol ; 15: 1439735, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39386363

RESUMO

Introduction: Plants are inherently connected with the microbiome, which plays a crucial role in regulating various host plant biological processes, including immunity, nutrient acquisition, and resistance against abiotic and biotic stresses. Many factors affect the interaction between plants and microbiome. Methods and results: In this study, microbiome samples were collected from five niches (bulk soil, rhizoplane, root endosphere, phylloplane, and leaf endosphere) across four developmental stages (seedling, flowering, podding, and maturity) of various soybean varieties. Composition and structure of bacterial and fungal communities were analyzed using 16S rRNA gene and ITS (Internally Transcribed Spacer) region amplicon sequencing. It was observed that both niches and developmental stages significantly impact on the assembly and composition of soybean microbiome. However, variety, presence of a transgene, and glyphosate application had minimal effects on microbial communities. The dominant microbiome varied across the five niches, with most containing beneficial microbial communities capable of promoting plant growth or increasing disease resistance. Types and abundance of the dominant microbes affected network stability, potentially resulting in functional changes in different ecological niches. Conclusion: This study provides theoretical evidence for microbial protection of plants against diseases and demonstrates that systematic analysis of the composition and diversity of soybean microbiomes can contribute to the development of biological control technologies.

5.
Food Chem ; 464(Pt 2): 141754, 2024 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-39461312

RESUMO

Flavonoids are found ubiquitous in dietary sources with potential antioxidant properties, and have received widespread attention for their health benefits. Nuts, rich in flavonoids, are popular among consumers for their crunchy flavor and nutritious content. The review summarizes studies pertaining to the diverse types and distribution of flavonoids in nuts, their potential health benefits, as well as management strategies for flavonoids accumulation and enhancement across the whole agro-food chain, including the selection of nut varieties, the suitable growing conditions, the optimal harvesting period of nuts, and appropriate post-harvest measures, such as chemical conditioning, ideal storage conditions, and post-harvest processing methods. Furthermore, associated metabolic pathways, and applied metabolic engineering to improve flavonoids´ levels in nuts are described. This review examines the application of flavonoids biofortification in nuts across the agro-food chain, exploring its potential for sustainable development in the nut flavonoids industry, and emphasizing its importance for people's diet and health.

6.
Cerebrovasc Dis ; 53(4): 501-508, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39250890

RESUMO

INTRODUCTION: The popular traditional Chinese medicine (TCM) compound FYTF-919 (Zhong Feng Xing Nao prescription) may improve outcome from acute intracerebral hemorrhage (ICH) through effects on brain edema, hematoma absorption, and the immune system. This study is to assess whether FYTF-919 is safe and effective as compared to matching placebo treatment in patients with acute ICH. METHODS: The ongoing Chinese Herbal medicine in patients with Acute INtracerebral hemorrhage (CHAIN) is a multicenter, prospective, randomized, double-blind placebo-controlled trial of FYTF-919 in patients with acute ICH at 20-30 hospital sites in China. Eligible ICH patients presenting within 48 h after symptom onset are randomly allocated to receive either FYTF-919 (100 mL per day × 28 d, oral) or matching placebo. A sample size of 1,504 patients is estimated to provide 90% power (α 0.05) to detect a ≥20% improvement in average utility-weight scores on the modified Rankin scale (UW-mRS) assessed at 90 days, with 6% non-adherence and 10% lost to follow-up. The primary efficacy outcome is UW-mRS at 90 days. Secondary outcomes include binary measures of the mRS, neurological impairment on the National Institute of Health Stroke Scale, and health-related quality of life on the EuroQol EQ-5D-5L scale at different time points over 6 months of follow-up. The key safety measure is serious adverse events. CONCLUSION: CHAIN is on schedule to provide reliable evidence over the benefits of a popular herbal TCM for the treatment of acute ICH.


Assuntos
Hemorragia Cerebral , Medicamentos de Ervas Chinesas , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Método Duplo-Cego , Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/uso terapêutico , Hemorragia Cerebral/tratamento farmacológico , Resultado do Tratamento , Estudos Prospectivos , China , Fatores de Tempo , Recuperação de Função Fisiológica , Estudos Multicêntricos como Assunto , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Doença Aguda , Avaliação da Deficiência , Estado Funcional , Adulto
7.
Acta Pharm Sin B ; 14(9): 4164-4173, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39309499

RESUMO

Viruses often manipulate ubiquitination pathways to facilitate their replication and pathogenesis. CUL2ZYG11B known as the substrate receptor of cullin-2 RING E3 ligase, is bound by SARS-CoV-2 ORF10 to increase its E3 ligase activity, leading to degradation of IFT46, a protein component of the intraflagellar transport (IFT) complex B. This results in dysfunctional cilia, which explains certain symptoms that are specific to COVID-19. However, the precise molecular mechanism of how ORF10 recognizes CUL2ZYG11B remains unknown. Here, we determined the crystal structure of CUL2ZYG11B complexed with the N-terminal extension (NTE) of SARS-CoV-2 ORF10 (2.9 Å). The structure reveals that the ORF10 N-terminal heptapeptide (NTH) mimics the Gly/N-degron to bind CUL2ZYG11B. Mutagenesis studies identified key residues within ORF10 that are key players in its interaction with CUL2ZYG11B both in ITC assay and in vivo cells. In addition, we prove that enhancement of CUL2ZYG11B activity for IFT46 degradation by which ORF10-mediated correlates with the binding affinity between ORF10 and CUL2ZYG11B. Finally, we used a Global Protein Stability system to show that the NTH of ORF10 mimics the Gly/N-degron motif, thereby binding competitively to CUL2ZYG11B and inhibiting the degradation of target substrates bearing the Gly/N-degron motif. Overall, this study sheds light on how SARS-CoV-2 ORF10 exploits the ubiquitination machinery for proteasomal degradation, and offers valuable insights for optimizing PROTAC-based drug design based on NTH CUL2ZYG11B interaction, while pinpointing a promising target for the development of treatments for COVID-19.

8.
Cerebrovasc Dis ; : 1-7, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39236681

RESUMO

INTRODUCTION: The fourth INTEnsive ambulance-delivered blood pressure Reduction in hyper-ACute stroke Trial (INTERACT4) is a large-scale, multicenter, prospective, randomized, open-label, blinded endpoint assessment trial, initiated in an ambulance in China, aiming at evaluating the effectiveness and safety of prehospital blood pressure (BP) lowering in patients with suspected acute stroke and elevated BP. A prespecified process evaluation is intended to explore the implementation of the trial intervention, provide support to interpret the trial outcomes and put forward suggestions to scale up the intervention in broader settings in the future. METHODS: This process evaluation is a mixed-methods design, and follows the Normalization Process Theory (NPT) and the UK Medical Research Council (UK MRC) guidance. Fidelity, reach, acceptability, appropriateness, adoption, sustainability, and relevant contextual factors and mechanisms affecting the implementation of prehospital early intensive BP-lowering treatment will be analyzed. Semi-structured interviews with ambulance staff, ward and emergency department clinicians, and nurses are undertaken to explore perceptions of the intervention, contextual factors, and potential suggestions for future implementation in practice. Data from observational records, surveys, conventional monitoring data, on-site records, and case report forms will be analyzed to understand background care and context. CONCLUSION: The process evaluation of INTERACT4 will provide insights for the implementation of prehospital early intensive BP-lowering intervention in different health systems and help better explain the trial results for further scale up.

9.
J Am Heart Assoc ; 13(18): e036109, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39258531

RESUMO

BACKGROUND: This study was conducted to determine optimal predictive ability of National Institutes of Health Stroke Scale (NIHSS) measurements at baseline, 24 hours, and change from baseline to 24 hours after thrombolysis on functional recovery in patients with acute ischemic stroke who participated in the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study). METHODS AND RESULTS: ENCHANTED was an international, multicenter, 2×2 quasifactorial, prospective, randomized open trial of low-dose versus standard-dose intravenous alteplase and intensive versus guideline-recommended blood pressure lowering in thrombolysis-eligible patients with acute ischemic stroke. Absolute (baseline minus 24 hours) and percentage (absolute change/baseline × 100) changes in NIHSS scores were calculated. Receiver operating characteristic curve analyses assessed performance of different NIHSS measurements on 90-day favorable functional recovery (modified Rankin Scale [mRS] score 0-2) and excellent functional recovery (mRS score 0-1). Youden index was used to identify optimal predictor cutoff points. A total of 4410 patients in the ENCHANTED trial were enrolled. The 24-hour NIHSS score had the highest discriminative ability for predicting favorable 90-day functional recovery (mRS score 0-2; area under the curve 0.866 versus 0.755, 0.689, 0.764; P<0.001) than baseline, absolute, and percentage change of NIHSS score, respectively. The optimal cutoff point of 24-hour NIHSS score for predicting favorable functional recovery was ≤4 (sensitivity 66.5%, specificity 87.1%, adjusted odds ratio, 9.44 [95% CI, 7.77-11.48]). The 24-hour NIHSS score (≤3) was the best predictor of 90-day excellent functional recovery (mRS score 0-1). Findings were consistent across subgroups, including sex, race, baseline NIHSS score, stroke subtype, and age. CONCLUSIONS: In thrombolysis-eligible patients with acute ischemic stroke, 24-hour NIHSS score (optimal cutpoint of 4) is the strongest predictor of 90-day functional recovery over baseline and early change of NIHSS score. REGISTRATION: URL: https://clinicaltrials.gov. Unique Identifier: NCT01422616.


Assuntos
Fibrinolíticos , AVC Isquêmico , Recuperação de Função Fisiológica , Terapia Trombolítica , Ativador de Plasminogênio Tecidual , Humanos , Masculino , Feminino , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/fisiopatologia , AVC Isquêmico/diagnóstico , Idoso , Terapia Trombolítica/métodos , Ativador de Plasminogênio Tecidual/administração & dosagem , Ativador de Plasminogênio Tecidual/uso terapêutico , Fibrinolíticos/uso terapêutico , Fibrinolíticos/administração & dosagem , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo , Valor Preditivo dos Testes , Resultado do Tratamento , Prognóstico , Índice de Gravidade de Doença , Estado Funcional , Avaliação da Deficiência , Idoso de 80 Anos ou mais
10.
Plant Dis ; 2024 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-39342962

RESUMO

Strawberry anthracnose, caused by Colletotrichum spp., is a devastating disease that significantly reduces strawberry yield and quality. This study aimed to develop a simple diagnostic method to detect infection by the Colletotrichum gloeosporioides complex (CGSC), the most predominant and virulent Colletotrichum species complex causing strawberry anthracnose in China. In this study, a Cas12aVIP diagnostic method was developed for the rapid detection of CGSC in strawberry seedlings. This method targets the ß-tubulin gene and combines recombinase polymerase amplification (RPA), the CRISPR/Cas12a system, and a cationic-conjugated polythiophene derivative [poly(3-(3'-N,N,N-triethylamino-1'-propyloxy)-4-methyl-2,5-thiophene hydrochloride) (PMNT)] mixed with single-stranded DNA (ssDNA). This method shows high sensitivity (ten copies per reaction) and no cross-reactivity against related pathogens. The entire procedure, from sample to result, can be completed within 50 min, including simplified DNA extraction (15 min), RPA reaction (37°C for 20 min), CRISPR/Cas12a detection (37°C for 10 min), and visual detection by the naked eye (1-2 min). Furthermore, the Cas12aVIP assay successfully detected CGSC in naturally infected strawberry seedling samples in field conditions. Asymptomatic infected plants and plant residues have been identified as primary inoculum sources for CGSC. This method enables visible detection without the need for expensive equipment or specialized technical skills, thereby offering an efficient and straightforward approach for detecting CGSC in strawberries. The newly developed detection method can be used to promote healthier strawberry production.

11.
Colloids Surf B Biointerfaces ; 244: 114183, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39208607

RESUMO

One way to effectively address endophyte infection and loosening is the creation of multifunctional coatings that combine anti-inflammatory, antibacterial, and vascularized osteogenesis. This study started with the preparation of strontium-doped titanium dioxide nanotubes (STN) on the titanium surface. Next, tannic acid (TA), gentamicin sulfate (GS), and pluronic F127 (PF127) were successfully loaded into the STN via layer-by-layer self-assembly, resulting in the STN@TA-GS/PF composite coatings. The findings demonstrated the excellent hydrophilicity and bioactivity of the STN@TA-GS/PF coating. STN@TA-GS/PF inhibited E. coli and S. aureus in vitro to a degree of roughly 80.95 % and 92.45 %, respectively. Cellular investigations revealed that on the STN@TA-GS/PF surface, the immune-system-related RAW264.7, the vasculogenic HUVEC, and the osteogenic MC3T3-E1 showed good adhesion and proliferation activities. STN@TA-GS/PF may influence RAW264.7 polarization toward the M2-type and encourage MC3T3-E1 differentiation toward osteogenesis at the molecular level. Meanwhile, the STN@TA-GS/PF coating achieved effective removal of ROS within HUVEC and significantly promoted angiogenesis. In both infected and non-infected bone defect models, the STN@TA-GS/PF material demonstrated strong anti-inflammatory, antibacterial, and vascularization-promoting osteogenesis properties. In addition, STN@TA-GS/PF had good hemocompatibility and biosafety. The three-step process used in this study to modify the titanium surface for several purposes gave rise to a novel concept for the clinical design of antimicrobial coatings with immunomodulatory properties.


Assuntos
Antibacterianos , Anti-Inflamatórios , Materiais Revestidos Biocompatíveis , Escherichia coli , Nanotubos , Próteses e Implantes , Staphylococcus aureus , Estrôncio , Titânio , Titânio/química , Titânio/farmacologia , Nanotubos/química , Camundongos , Animais , Estrôncio/química , Estrôncio/farmacologia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Staphylococcus aureus/efeitos dos fármacos , Humanos , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Escherichia coli/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Células RAW 264.7 , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Propriedades de Superfície , Taninos/química , Taninos/farmacologia , Osteogênese/efeitos dos fármacos , Poloxâmero/química , Poloxâmero/farmacologia , Proliferação de Células/efeitos dos fármacos , Gentamicinas/farmacologia , Gentamicinas/química , Tamanho da Partícula
12.
Cerebrovasc Dis ; 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39043146

RESUMO

INTRODUCTION: The traditional Chinese medicine (TCM) herbal compound FYTF-919 (Zhong Feng Xing Nao prescription) may improve outcome from acute intracerebral hemorrhage (ICH) by reducing brain edema, hematoma absorption, and enhancement of the immune system. We outline the statistical analysis plan (SAP) for the Chinese Herbal medicine in Acute INtracerebral haemorrhage (CHAIN) study. DESIGN: CHAIN is a multicenter, prospective, randomized, double-blind, placebo-controlled trial being undertaken at 20-30 hospitals in China. After the completion of eligibility checks, patients are randomly allocated to FYTF-919 (100 mL per day, oral) or matching placebo over 28 days. A sample size of 1504 patients is estimated to provide 90% power (α 0.05) for a 0.06 absolute improvement in the primary outcome of utility-weighted modified Rankin scale scores at 90 days, analyzed by general linear regression. METHODS: The statistical analysis plan was developed by the study statistician, principal investigators, international experts, and the study project manager. The plan provides details for analyzing baseline characteristics, patient management, and outcomes. It includes provisions for covariate adjustments, subgroup analysis, the handling missing data, and in the conduct of sensitivity analyzes. RESULTS: A predefined statistical analysis plan was established for CHAIN, facilitating transparent and verifiable analysis. CONCLUSIONS: The CHAIN statistical analysis plan was prospectively developed with a focus on maintaining high-quality standards of internal validity to minimise potential analysis biases. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05066620).

13.
New Phytol ; 243(5): 1823-1839, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39005107

RESUMO

Cone enlargement is a crucial process for seed production and reproduction in gymnosperms. Most of our knowledge of cone development is derived from observing anatomical structure during gametophyte development. Therefore, the exact molecular mechanism underlying cone enlargement after fertilization is poorly understood. Here, we demonstrate that sucrose promotes cone enlargement in Torreya grandis, a gymnosperm species with relatively low rates of cone enlargement, via the TgNGA1-TgWRKY47-TgEXPA2 pathway. Cell expansion plays a significant role in cone enlargement in T. grandis. 13C labeling and sucrose feeding experiments indicated that sucrose-induced changes in cell size and number contribute to cone enlargement in this species. RNA-sequencing analysis, transient overexpression in T. grandis cones, and stable overexpression in tomato (Solanum lycopersicum) suggested that the expansin gene TgEXPA2 positively regulates cell expansion in T. grandis cones. The WRKY transcription factor TgWRKY47 directly enhances TgEXPA2 expression by binding to its promoter. Additionally, the NGATHA transcription factor TgNGA1 directly interacts with TgWRKY47. This interaction suppresses the DNA-binding ability of TgWRKY47, thereby reducing its transcriptional activation on TgEXPA2 without affecting the transactivation ability of TgWRKY47. Our findings establish a link between sucrose and cone enlargement in T. grandis and elucidate the potential underlying molecular mechanism.


Assuntos
Proteínas de Plantas , Sacarose , Taxaceae , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas , Regiões Promotoras Genéticas/genética , Ligação Proteica/efeitos dos fármacos , Solanum lycopersicum/genética , Solanum lycopersicum/crescimento & desenvolvimento , Sacarose/metabolismo , Sacarose/farmacologia , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Taxaceae/genética , Taxaceae/crescimento & desenvolvimento
14.
Burns Trauma ; 12: tkae013, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38957661

RESUMO

The unique ability of piezoelectric materials to generate electricity spontaneously has attracted widespread interest in the medical field. In addition to the ability to convert mechanical stress into electrical energy, piezoelectric materials offer the advantages of high sensitivity, stability, accuracy and low power consumption. Because of these characteristics, they are widely applied in devices such as sensors, controllers and actuators. However, piezoelectric materials also show great potential for the medical manufacturing of artificial organs and for tissue regeneration and repair applications. For example, the use of piezoelectric materials in cochlear implants, cardiac pacemakers and other equipment may help to restore body function. Moreover, recent studies have shown that electrical signals play key roles in promoting tissue regeneration. In this context, the application of electrical signals generated by piezoelectric materials in processes such as bone healing, nerve regeneration and skin repair has become a prospective strategy. By mimicking the natural bioelectrical environment, piezoelectric materials can stimulate cell proliferation, differentiation and connection, thereby accelerating the process of self-repair in the body. However, many challenges remain to be overcome before these concepts can be applied in clinical practice, including material selection, biocompatibility and equipment design. On the basis of the principle of electrical signal regulation, this article reviews the definition, mechanism of action, classification, preparation and current biomedical applications of piezoelectric materials and discusses opportunities and challenges for their future clinical translation.

15.
Phytomedicine ; 133: 155912, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39068761

RESUMO

BACKGROUND: Interstitial lung disease (ILD) is a common complication of rheumatoid arthritis (RA) that plays a significant role in the morbidity and mortality of individuals with this condition. In clinical settings, Si Miao Wan (SMW), a traditional Chinese medicine, is often utilized for the management of RA, as it is believed to possess properties that aid in reducing inflammation, eliminating excess moisture, and alleviating joint pain. PURPOSE: The primary objective of this investigation was to elucidate the potential mechanism of RA-ILD prevention from the perspective of ferroptosis mediated by SMW. METHODS: UPLC-Q-TOF/MS and network pharmacology were employed to forecast the potential targets of SMW for the early prevention of RA-ILD. Following this, HE staining, metabolomics, and RT-PCR were utilized to investigate the mechanism by which SMW prevents RA-ILD at an early stage. RESULTS: Following six weeks of continuous administration of SMW extract at a dosage of 2.16 g/kg/day, it was observed that SMW exhibited early preventive effects against RA-ILD. Metabolomics analysis revealed seven potential biomarkers linked to the pharmacological efficacy of SMW in the early prevention of RA-ILD. Additionally, network pharmacology analysis suggested that SMW may exert its therapeutic effects on RA-ILD by modulating signaling pathways associated with lipid metabolism, atherosclerosis, TNF, and IL-17. Ultimately, through the integration of metabolomics and network pharmacology analysis, along with subsequent verification, it was determined that the early prevention of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) by Shenmai injection (SMW) is associated with the ferroptosis pathway. CONCLUSION: This research offers preliminary insights into the potential mechanism by which traditional Chinese medicine Shen Mai Wan (SMW) may mitigate the early onset of Rheumatoid Arthritis-Interstitial Lung Disease (RA-ILD) via the process of ferroptosis. Furthermore, it establishes a theoretical framework for the development of innovative SMW-based pharmaceuticals for the management of RA-ILD. The signal proteins implicated in this process are anticipated to emerge as crucial targets for the prevention of RA-ILD.


Assuntos
Artrite Reumatoide , Medicamentos de Ervas Chinesas , Ferroptose , Doenças Pulmonares Intersticiais , Metabolômica , Farmacologia em Rede , Ferroptose/efeitos dos fármacos , Artrite Reumatoide/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Animais , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/prevenção & controle , Masculino , Biomarcadores , Medicina Tradicional Chinesa , Camundongos
16.
Cancer Med ; 13(12): e7439, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38924382

RESUMO

BACKGROUND: Patients diagnosed with advanced stage cancer face an elevated risk of suicide. We aimed to develop a suicidal ideation (SI) risk prediction model in patients with advanced cancer for early warning of their SI and facilitate suicide prevention in this population. PATIENTS AND METHODS: We consecutively enrolled patients with multiple types of advanced cancers from 10 cancer institutes in China from August 2019 to December 2020. Demographic characteristics, clinicopathological data, and clinical treatment history were extracted from medical records. Symptom burden, psychological status, and SI were assessed using the MD Anderson Symptom Inventory (MDASI), Hospital Anxiety and Depression Scale (HADS), and Patient Health Questionnaire-9 (PHQ-9), respectively. A multivariable logistic regression model was employed to establish the model structure. RESULTS: In total, 2814 participants were included in the final analysis. Nine predictors including age, sex, number of household members, history of previous chemotherapy, history of previous surgery, MDASI score, HADS-A score, HADS-D score, and life satisfaction were retained in the final SI prediction model. The model achieved an area under the curve (AUC) of 0.85 (95% confidential interval: 0.82-0.87), with AUCs ranging from 0.75 to 0.95 across 10 hospitals and higher than 0.83 for all cancer types. CONCLUSION: This study built an easy-to-use, good-performance predictive model for SI. Implementation of this model could facilitate the incorporation of psychosocial support for suicide prevention into the standard care of patients with advanced cancer.


Assuntos
Neoplasias , Ideação Suicida , Humanos , Masculino , Feminino , Neoplasias/psicologia , China/epidemiologia , Pessoa de Meia-Idade , Idoso , Medição de Risco , Adulto , Fatores de Risco
17.
Int J Mol Sci ; 25(11)2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38891770

RESUMO

Terpene aroma compounds are key quality attributes of postharvest Torreya grandis nuts, contributing to their commercial value. However, terpene biosynthesis and regulatory networks in different T. grandis cvs. are still poorly understood. Here, chief cvs. 'Xi Fei' and 'Xiangya Fei' were investigated for their differences in terpene biosynthesis and gene expression levels during postharvest ripening using headspace solid-phase microextraction (HS-SPME) coupled with gas chromatography-mass spectrometry (GC-MS) and transcriptomic datasets. A total of 28 and 22 aroma compounds were identified in 'Xi Fei' and 'Xiangya Fei', respectively. Interestingly, differences in aroma composition between the two cvs. were mostly attributed to D-limonene and α-pinene levels as key determinants in Torreya nuts' flavor. Further, transcriptome profiling, correlation analysis, and RT-qPCR annotated two novel genes, TgTPS1 in 'Xi Fei' and TgTPS2 in 'Xiangya Fei', involved in terpene biosynthesis. In addition, six transcription factors (TFs) with comparable expression patterns to TgTPS1 and four TFs to TgTPS2 were identified via correlation analysis of a volatile and transcriptome dataset to be involved in terpene biosynthesis. Our study provides novel insight into terpene biosynthesis and its regulation at the molecular level in T. grandis nut and presents a valuable reference for metabolic engineering and aroma improvement in this less explored nut.


Assuntos
Cromatografia Gasosa-Espectrometria de Massas , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Terpenos , Terpenos/metabolismo , Cromatografia Gasosa-Espectrometria de Massas/métodos , Perfilação da Expressão Gênica/métodos , Transcriptoma , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Odorantes/análise
18.
Cancer Med ; 13(11): e7330, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38845478

RESUMO

OBJECTIVES: Patients with advanced colorectal cancer (CRC) have multiple concurrent physical and psychological symptoms. This study aimed to explore the relationship between anxiety, depression, and symptom burden in advanced CRC. METHODS: A multicenter cross-sectional study was conducted in 10 cancer centers from geographically and economically diverse sites in China. A total of 454 patients with advanced CRC completed the Hospital Anxiety and Depression Scale and the MD Anderson Symptom Inventory. Multiple regression analysis was applied to explore the relationship between anxiety, depression and symptom burden. RESULTS: About one-third of the patients showed symptoms of anxiety or depression. Patients with anxiety or depression reported significantly higher symptom burden than those without (p < 0.001). Patients with anxiety or depression reported a higher proportion of moderate-to-severe (MS) symptom number than those without (p < 0.001). About 52% of the patients with anxiety or depression reported at least three MS symptoms. The prevalence of MS symptoms was ranging from 7.3% (shortness of breath) to 22% (disturbed sleep), and in patients with anxiety or depression was 2-10 times higher than in those without (p < 0.001). Disease stage (ß = -2.55, p = 0.003), anxiety (ß = 15.33, p < 0.001), and depression (ß = 13.63, p < 0.001) were associated with higher symptom burden. CONCLUSIONS: Anxiety and depression in patients with advanced cancer correlated with higher symptom burden. Findings may lead oncology professionals to pay more attention to unrecognized and untreated psychological symptoms in symptom management for advanced cancer patients.


Assuntos
Ansiedade , Neoplasias Colorretais , Depressão , Humanos , Neoplasias Colorretais/psicologia , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/complicações , Masculino , Feminino , Estudos Transversais , Pessoa de Meia-Idade , Depressão/epidemiologia , Depressão/etiologia , Depressão/psicologia , Ansiedade/epidemiologia , Ansiedade/psicologia , Idoso , China/epidemiologia , Prevalência , Adulto , Idoso de 80 Anos ou mais , Qualidade de Vida , Carga de Sintomas
19.
Front Microbiol ; 15: 1388669, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38873148

RESUMO

Introduction: Morchella esculenta is a popular edible fungus with high economic and nutritional value. However, the rot disease caused by Lecanicillium aphanocladii, pose a serious threat to the quality and yield of M. esculenta. Biological control is one of the effective ways to control fungal diseases. Methods and results: In this study, an effective endophytic B. subtilis A9 for the control of M. esculenta rot disease was screened, and its biocontrol mechanism was studied by transcriptome analysis. In total, 122 strains of endophytic bacteria from M. esculenta, of which the antagonistic effect of Bacillus subtilis A9 on L. aphanocladii G1 reached 72.2% in vitro tests. Biological characteristics and genomic features of B. subtilis A9 were analyzed, and key antibiotic gene clusters were detected. Scanning electron microscope (SEM) observation showed that B. subtilis A9 affected the mycelium and spores of L. aphanocladii G1. In field experiments, the biological control effect of B. subtilis A9 reached to 62.5%. Furthermore, the transcritome profiling provides evidence of B. subtilis A9 bicontrol at the molecular level. A total of 1,246 differentially expressed genes (DEGs) were identified between the treatment and control group. Gene Ontology (GO) enrichment analysis showed that a large number of DEGs were related to antioxidant activity related. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the main pathways were Nitrogen metabolism, Pentose Phosphate Pathway (PPP) and Mitogen-Activated Protein Kinases (MAPK) signal pathway. Among them, some important genes such as carbonic anhydrase CA (H6S33_007248), catalase CAT (H6S33_001409), tRNA dihydrouridine synthase DusB (H6S33_001297) and NAD(P)-binding protein NAD(P) BP (H6S33_000823) were found. Furthermore, B. subtilis A9 considerably enhanced the M. esculenta activity of Polyphenol oxidase (POD), Superoxide dismutase (SOD), Phenylal anineammonia lyase (PAL) and Catalase (CAT). Conclusion: This study presents the innovative utilization of B. subtilis A9, for effectively controlling M. esculenta rot disease. This will lay a foundation for biological control in Morchella, which may lead to the improvement of new biocontrol agents for production.

20.
Angew Chem Int Ed Engl ; 63(35): e202409145, 2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-38869085

RESUMO

Metal hexacyanoferrates (HCFs) are regarded as promising cathode materials for potassium-ion batteries (PIBs) on account of their low cost and high energy density. However, the difficult-to-remove [Fe(CN)6] vacancies and crystal water lead to structural instability and capacity deterioration as well as the stereotype of poor thermostability of conventional HCFs. Herein, we report (100) face-oriented potassium magnesium hexacyanoferrate (KMgHCF) nanoplates with low [Fe(CN)6] vacancies and high crystallinity, enabling thermostability up to 550 °C, high-temperature carbon coating and crystal water elimination. The as-obtained KMgHCF/C nanoplates exhibit superior potassium storage properties, including a large reversible capacity of 84.6 mAh g-1, a high voltage plateau of 3.87 V, excellent long-term cycling performance over 15000 cycles and high rate capability at 5 A g-1. The unprecedented cycling stability of KMgHCF/C is attributed to the synergistic effect of a highly reversible two-phase reaction, low [Fe(CN)6] vacancies and no crystal water, a specially exposed steady (100) surface, and a protective carbon coating. This work provides a new material selection and modification strategy for the practical application of HCFs in PIBs.

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