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1.
iScience ; 27(9): 110710, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39262792

RESUMO

Mitochondria play important roles in cell fate, calcium signaling, mitophagy, and the signaling through reactive oxygen species (ROS). Recently, mitochondria are considered as a signaling organelle in the cell and communicate with other organelles to constitute the mitochondrial information processing system (MIPS) that transduce input-to-output biological information. The success in immunotherapy, a concept of systemic therapy, has been proved to be dependent on paracrine interactions within the tumor microenvironment (TME) and distant organs including microbiota and immune components. We will adopt a broader view from the concept of TME to tumor micro- and macroenvironment (TM 2 E) or tumor-organ ecosystem (TOE). In this review, we will discuss the role of mitochondrial signaling by mitochondrial ROS, calcium flux, metabolites, mtDNA, vesicle transportation, and mitochondria-derived peptide in the TME and TOE, in particular immune regulation and effective cancer immunotherapy.

2.
Cell Metab ; 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39293433

RESUMO

Adipose tissue macrophages (ATMs) play important roles in maintaining adipose tissue homeostasis and orchestrating metabolic inflammation. Given the extensive functional heterogeneity and phenotypic plasticity of ATMs, identification of the authentically pathogenic ATM subpopulation under obese setting is thus necessitated. Herein, we performed single-nucleus RNA sequencing (snRNA-seq) and unraveled a unique maladaptive ATM subpopulation defined as ATF4hiPDIA3hiACSL4hiCCL2hi inflammatory and metabolically activated macrophages (iMAMs), in which PDIA3 is required for the maintenance of their migratory and pro-inflammatory properties. Mechanistically, ATF4 serves as a metabolic stress sensor to transcribe PDIA3, which then imposes a redox control on RhoA activity and strengthens the pro-inflammatory and migratory properties of iMAMs through RhoA-YAP signaling. Administration of Pdia3 small interfering RNA (siRNA)-loaded liposomes effectively repressed adipose inflammation and high-fat diet (HFD)-induced obesity. Together, our data support that strategies aimed at targeting iMAMs by suppressing PDIA3 expression or activity could be a viable approach against obesity and metabolic disorders in clinical settings.

4.
Adv Sci (Weinh) ; : e2309459, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39049738

RESUMO

Class IIa histone deacetylases (Class IIa HDACs) play critical roles in regulating essential cellular metabolism and inflammatory pathways. However, dissecting the specific roles of each class IIa HDAC isoform is hindered by the pan-inhibitory effect of current inhibitors and a lack of tools to probe their functions beyond epigenetic regulation. In this study, a novel PROTAC-based compound B4 is developed, which selectively targets and degrades HDAC7, resulting in the effective attenuation of a specific set of proinflammatory cytokines in both lipopolysaccharide (LPS)-stimulated macrophages and a mouse model. By employing B4 as a molecular probe, evidence is found for a previously explored role of HDAC7 that surpasses its deacetylase function, suggesting broader implications in inflammatory processes. Mechanistic investigations reveal the critical involvement of HDAC7 in the Toll-like receptor 4 (TLR4) signaling pathway by directly interacting with the TNF receptor-associated factor 6 and TGFß-activated kinase 1 (TRAF6-TAK1) complex, thereby initiating the activation of the downstream mitogen-activated protein kinase/nuclear factor-κB (MAPK/NF-κB) signaling cascade and subsequent gene transcription. This study expands the insight into HDAC7's role within intricate inflammatory networks and highlights its therapeutic potential as a novel target for anti-inflammatory treatments.

5.
Cancer Immunol Immunother ; 73(9): 175, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38953994

RESUMO

Tumor immunotherapies targeting PD-(L)1 exhibit anti-tumor efficacy in only 10-30% of patients with various cancers. Literature has demonstrated that a "hot tumor" which contains high T lymphocytes in the tumor microenvironment exhibits a better response to immunotherapies than a "cold tumor." This study aimed to investigate whether tumor-intrinsic IFNα and CXCL10 determine the recruitment and activation of CD8+ T cells to become "hot tumor." In this study, we found that CXCL10 overexpressed in a variety of tumors including lung, colon, and liver tumors with a correlation with PD-L1. High PD-L1 and CXCL10 are associated with better survival rates in tumor patients receiving immunotherapies. IFNs-downstream transcriptional factor IRF-1 and STAT1 were correlated with PD-L1 and CXCL10 expression. We demonstrated that IRF-1 and STAT1 were both bound with the promoters of PD-L1 and CXCL10, sharing the same signaling pathway and determining IFNs-mediated PD-L1 and CXCL10 expression. In addition, IFNα significantly increased activation marker IFNγ in PBMCs, promoting M1 type monocyte differentiation, CD4+ T, and CD8+ T cell activation. Particularly, we found that CD8+ T lymphocytes abundantly expressed CXCR3, a receptor of CXCL10, by flow cytometry, indicating that tumor-intrinsic CXCL10 potentially recruited CD8+ T in tumor microenvironment. To demonstrate the hypothesis, immunotherapy-sensitive CT26 and immunotherapy-resistant LL/2 were used and we found that CT26 cells exhibited higher IFNα, IFNγ, CXCL10, and PD-L1 levels compared to LL/2, leading to higher IFNγ expression in mouse splenocytes. Moreover, we found that CD8+ T cells were recruited by CXCL10 in vitro, whereas SCH546738, an inhibitor of CXCR3, inhibited T cell migration and splenocytes-mediated anti-tumor effect. We then confirmed that CT26-derived tumor was sensitive to αPD-L1 immunotherapy and LL/2-tumor was resistant, whereas αPD-L1 significantly increased T lymphocyte activation marker CD107a in CT26-derived BALB/c mice. In conclusion, this study revealed that CXCL10 expression is correlated with PD-L1 in tumors, sharing the same signaling pathway and associating with better immunotherapeutic efficacy. Further evidence in the syngeneic tumor models demonstrated that immunotherapy-sensitive CT26 intrinsically exhibited higher IFNα and CXCL10 compared to immunotherapy-resistant LL/2 to recruit and activate CD8+ T cells in the tumor microenvironment, exhibiting "hot tumor" characteristic of sensitizing αPD-L1 immunotherapies.


Assuntos
Quimiocina CXCL10 , Imunoterapia , Interferon-alfa , Microambiente Tumoral , Quimiocina CXCL10/metabolismo , Quimiocina CXCL10/imunologia , Microambiente Tumoral/imunologia , Animais , Camundongos , Humanos , Imunoterapia/métodos , Neoplasias/imunologia , Neoplasias/terapia , Ativação Linfocitária/imunologia , Linhagem Celular Tumoral , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Antígeno B7-H1/metabolismo , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Feminino , Fator de Transcrição STAT1/metabolismo
6.
Angew Chem Int Ed Engl ; 63(39): e202407228, 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-38975669

RESUMO

Three functionalized thienopyrazines (TPs), TP-MN (1), TP-CA (2), and TPT-MN (3) were designed and synthesized as self-assembled monolayers (SAMs) deposited on the NiOx film for tin-perovskite solar cells (TPSCs). Thermal, optical, electrochemical, morphological, crystallinity, hole mobility, and charge recombination properties, as well as DFT-derived energy levels with electrostatic surface potential mapping of these SAMs, have been thoroughly investigated and discussed. The structure of the TP-MN (1) single crystal was successfully grown and analyzed to support the uniform SAM produced on the ITO/NiOx substrate. When we used NiOx as HTM in TPSC, the device showed poor performance. To improve the efficiency of TPSC, we utilized a combination of new organic SAMs with NiOx as HTM, the TPSC device exhibited the highest PCE of 7.7 % for TP-MN (1). Hence, the designed NiOx/TP-MN (1) acts as a new model system for the development of efficient SAM-based TPSC. To the best of our knowledge, the combination of organic SAMs with anchoring CN/CN or CN/COOH groups and NiOx as HTM for TPSC has never been reported elsewhere. The TPSC device based on the NiOx/TP-MN bilayer exhibits great enduring stability for performance, retaining ~80 % of its original value for shelf storage over 4000 h.

7.
Exp Brain Res ; 242(8): 1933-1946, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38900160

RESUMO

Visuospatial attention (VSA) is a cognitive function that enables athletes, particularly those engaged in open-skill sports, to allocate attentional resources efficiently to the appropriate target and in the appropriate direction. Studies have indicated that expert players exhibit superior cognitive performance to that of novices. However, no study has investigated differences in VSA performance among elite, expert, and intermediate badminton players or the potential neurophysiological mechanisms underlying such differences. Accordingly, the present study explored neuropsychological and neurophysiological parameters during VSA tasks among badminton players of varying competitive levels. The study included 54 participants and divided them into three groups according to their competition records: elite (n = 18), expert (n = 18), and intermediate (n = 18). Their neuropsychological performance and brain event-related potentials (ERPs) during the Posner cueing paradigm were collected. Although the three groups did not differ in their accuracy rates, ERP N2 amplitudes, or N2 or P3 latencies, the elite and expert groups exhibited notably faster reaction times and more pronounced P3 amplitudes than did the intermediate group during the cognitive task. However, we did not observe these between-group differences when we controlled for the covariate training years. Additionally, the elite and expert groups exhibited comparable neurocognitive performance. These findings indicate that badminton players' competitive levels influence their VSA. However, the beneficial effects on neuropsychological and neurophysiological performance could stabilize after a certain level of badminton competence is reached. Year of training could also be a major factor influencing badminton players' neurocognitive performance in VSA tasks.


Assuntos
Atenção , Eletroencefalografia , Potenciais Evocados , Esportes com Raquete , Percepção Espacial , Humanos , Atenção/fisiologia , Masculino , Esportes com Raquete/fisiologia , Adulto Jovem , Potenciais Evocados/fisiologia , Percepção Espacial/fisiologia , Adulto , Feminino , Percepção Visual/fisiologia , Tempo de Reação/fisiologia , Desempenho Psicomotor/fisiologia , Adolescente , Comportamento Competitivo/fisiologia , Desempenho Atlético/fisiologia
8.
Eur J Phys Rehabil Med ; 60(4): 621-633, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38888734

RESUMO

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative condition characterized by movement disorders and probable cognitive impairment. Exercise plays an important role in PD management, and recent studies have reported improvement in motor symptoms and cognitive function following aerobic and Tai Chi Chuan exercise. AIM: To explore the different effects of Tai Chi Chuan and aerobic exercise on the clinical motor status and neurocognitive performance of patients with early-stage PD. DESIGN: A randomized controlled trial. SETTING: Parkinson's Disease Center at Kaohsiung Chang Gung Memorial Hospital and National Cheng Kung University Hospital. POPULATION: Patients with idiopathic PD. METHODS: Fifty-six patients with PD were recruited and divided into three groups: aerobic exercise (AE, N.=14), Tai Chi Chuan exercise (TE, N.=16), and control (CG, N.=13). Before and after a 12-week intervention period, we used unified Parkinson's disease rating scale Part III (UPDRS-III) scores and neuropsychological (e.g., accuracy rates [ARs] and reaction times [RTs]) and neurophysiological (e.g., event-related potential [ERP] N2 and P3 latencies and amplitudes) parameters to respectively assess the patients' clinical motor symptoms and neurocognitive performance when performing a working memory (WM) task. RESULTS: Compared to baseline, UPDRS-III scores were significantly lower in the AE and TE groups after the intervention period, whereas those for the CG group were higher. In terms of the neurocognitive parameters, when performing the WM task after the intervention period, the AE group exhibited significantly faster RTs and larger ERP P3 amplitudes, the TE group exhibited an improvement only in ERP P3 amplitude, and the CG group exhibited a significantly reduced ERP P3 amplitude. However, neither the TE nor the AE group exhibited improved ARs and ERP N2 performance. CONCLUSIONS: The present study supported the distinct effectiveness of Tai Chi Chuan and aerobic exercise for improving motor symptoms and providing neurocognitive benefits in PD patients. CLINICAL REHABILITATION IMPACT: These results have important implications regarding the use of these exercise interventions for managing PD, particularly in the early stages.


Assuntos
Doença de Parkinson , Tai Chi Chuan , Humanos , Tai Chi Chuan/métodos , Doença de Parkinson/reabilitação , Doença de Parkinson/complicações , Doença de Parkinson/fisiopatologia , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Terapia por Exercício/métodos , Exercício Físico/fisiologia , Testes Neuropsicológicos , Resultado do Tratamento , Cognição/fisiologia
9.
J Ethnopharmacol ; 331: 118274, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38697410

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with reproductive dysfunction and metabolic abnormalities, particularly characterized by insulin resistance and chronic low-grade inflammation. Multiple clinical studies have clearly demonstrated the significant efficacy and safety of the combination of Bailing capsules (BL) in the treatment of PCOS, but its pharmacological effects and mechanisms still require further study. AIM OF THE STUDY: To evaluate the effect of BL on improving PCOS in mice and explore the mechanism. METHODS: In this study, Dehydroepiandrosterone (DHEA) injection was administered alone and in combination with a high-fat and high-sugar diet to induce PCOS-like mouse. They were randomly divided into five groups: normal group (N), PCOS group (P), Bailing capsule low-dose group (BL-L), Bailing capsule high-dose group (BL-H) and Metformin + Daine-35 group (M + D). Firstly, the effects of BL on ovarian lesions, serum hormone levels, HOMA-IR, intestinal barrier function, inflammation levels, along with the expression of IRS1, PI3K, AKT, TLR4, Myd88, NF-κB p65, TNF-α, IL-6, and Occludin of the ovary, liver and colon were investigated. Finally, the composition of the gut microbiome of fecal was tested. RESULTS: The administration of BL significantly reduced body weight, improved hormone levels, improved IR, and attenuated pathological damage to ovarian tissues, up-regulated the expression of IRS1, PI3K, and AKT in liver. It also decreased serum LPS, TNF-α, and IL-6 levels, while downregulating the expression of Myd88, TLR4, and NF-κB p65. Additionally, BL improved intestinal barrier damage and upregulated the expression of Occludin. Interestingly, the abundance of norank_f__Muribaculacea and Lactobacillus was down-regulated, while the abundance of Akkermansia was significantly up-regulated. CONCLUSION: The results of the study showed that BL exerts a treatment PCOS effect, which may be related to the modulation of the gut microbiota, the improvement of insulin resistance and the intestinal-derived LPS-TLR4 inflammatory pathway. Our research will provide a theoretical basis for the clinical treatment of PCOS.


Assuntos
Medicamentos de Ervas Chinesas , Lipopolissacarídeos , Síndrome do Ovário Policístico , Transdução de Sinais , Receptor 4 Toll-Like , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/induzido quimicamente , Animais , Feminino , Receptor 4 Toll-Like/metabolismo , Camundongos , Transdução de Sinais/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Resistência à Insulina , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Desidroepiandrosterona/farmacologia , Cápsulas , Intestinos/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Ovário/efeitos dos fármacos , Ovário/metabolismo , Ovário/patologia
10.
ACS Appl Mater Interfaces ; 16(19): 25042-25052, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38706304

RESUMO

Electrical double-layer transistors (EDLTs) have received extensive research attention owing to their exciting advantages of low working voltage, high biocompatibility, and sensitive interfacial properties in ultrasensitive portable sensing applications. Therefore, it is of great interest to reduce photodetectors' operating voltage and power consumption by utilizing photo-EDLT. In this study, a series of block copolymers (BCPs) of poly(4-vinylpyridine)-block-poly(ethylene oxide) (P4VP-b-PEO) with different compositions were applied to formulate polyelectrolyte with indigo carmine salt in EDLT. Accordingly, PEO conduces ion conduction in the BCP electrolyte and enhances the carrier transport capability in the semiconducting channel; P4VP boosts the photocurrent by providing charge-trapping sites during light illumination. In addition, the severe aggregation of PEO is mitigated by forming a BCP structure with P4VP, enhancing the stability and photoresponse of the photo-EDLT. By optimizing the BCP composition, EDLT comprising P4VP16k-b-PEO5k and indigo carmine provides the highest specific detectivity of 2.1 × 107 Jones, along with ultralow power consumptions of 0.59 nW under 450 nm light illumination and 0.32 pW under dark state. The results indicate that photo-EDLT comprising the BCP electrolyte is a practical approach to reducing phototransistors' operating voltage and power consumption.

11.
Bioorg Chem ; 147: 107394, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38691906

RESUMO

Epidermal growth factor receptor (EGFR) is one of the most studied drug targets for treating non-small-cell lung cancer (NSCLC). However, there are no approved inhibitors for the C797S resistance mutation caused by the third-generation EGFR inhibitor (Osimertinib). Therefore, the development of fourth-generation EGFR inhibitors is urgent. In this study, we clarified the structure-activity relationship of several synthesized compounds as fourth-generation inhibitors against human triple (Del19/T790M/C797S) mutation. Representative compound 52 showed potent inhibitory activity against EGFRL858R/T790M/C797S with an IC50 of 0.55 nM and significantly inhibited the proliferation of the Ba/F3 cell line harboring EGFRL858R/T790M/C797S with an IC50 of 43.28 nM. Moreover, 52 demonstrated good pharmacokinetic properties and excellent in vivo efficacy. Overall, the compound 52 can be considered a promising candidate for overcoming EGFR C797S-mediated mutations.


Assuntos
Acrilamidas , Compostos de Anilina , Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Proliferação de Células , Relação Dose-Resposta a Droga , Desenho de Fármacos , Resistencia a Medicamentos Antineoplásicos , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB , Neoplasias Pulmonares , Inibidores de Proteínas Quinases , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Receptores ErbB/genética , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Acrilamidas/farmacologia , Acrilamidas/química , Acrilamidas/síntese química , Relação Estrutura-Atividade , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/síntese química , Compostos de Anilina/farmacologia , Compostos de Anilina/química , Compostos de Anilina/síntese química , Compostos de Anilina/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Estrutura Molecular , Animais , Camundongos , Linhagem Celular Tumoral , Mutação , Indóis , Pirimidinas
12.
Small ; : e2401966, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38733223

RESUMO

While research on organic thermoelectric polymers is making significant progress in recent years, realization of a single polymer material possessing both thermoelectric properties and stretchability for the next generation of self-powered wearable electronics is a challenging task and remains an area yet to be explored. A new molecular engineering concept of "conjugated breaker" is employed to impart stretchability to a highly crystalline diketopyrrolepyrrole (DPP)-based polymer. A hexacyclic diindenothieno[2,3-b]thiophene (DITT) unit, with two 4-octyloxyphenyl groups substituted at the tetrahedral sp3-carbon bridges, is selected to function as the conjugated breaker that can sterically hinder intermolecular packing to reduce polymers' crystallinity. A series of donor-acceptor random copolymers is thus developed via polymerizing the crystalline DPP units with the DITT conjugated breakers. By controlling the monomeric DPP/DITT ratios, DITT30 reaches the optimal balance of crystalline/amorphous regions, exhibiting an exceptional power factor (PF) value up to 12.5 µW m-1 K-2 after FeCl3-doping; while, simultaneously displaying the capability to withstand strains exceeding 100%. More significantly, the doped DITT30 film possesses excellent mechanical endurance, retaining 80% of its initial PF value after 200 cycles of stretching/releasing at a strain of 50%. This research marks a pioneering achievement in creating intrinsically stretchable polymers with exceptional thermoelectric properties.

13.
J Org Chem ; 89(11): 7770-7779, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38738957

RESUMO

A visible-light-enabled photoredox radical cascade cyclization of 2-vinyl benzimidazole derivatives is developed. This chemistry is applicable to a wide range of N-aroyl 2-vinyl benzimidazoles as acceptors, and halo compounds, including alkyl halides, acyl chlorides and sulfonyl chlorides, as radical precursors. The Langlois reagent also serves as an effective partner in this photocatalytic oxidative cascade process. This protocol provides a robust alternative for rendering highly functionalized benzo[4,5]imidazo[1,2-b]isoquinolin-11(6H)-ones.

14.
World J Gastrointest Oncol ; 16(3): 945-967, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38577477

RESUMO

BACKGROUND: Gastric cancer (GC) is a highly aggressive malignancy with a heterogeneous nature, which makes prognosis prediction and treatment determination difficult. Inflammation is now recognized as one of the hallmarks of cancer and plays an important role in the aetiology and continued growth of tumours. Inflammation also affects the prognosis of GC patients. Recent reports suggest that a number of inflammatory-related biomarkers are useful for predicting tumour prognosis. However, the importance of inflammatory-related biomarkers in predicting the prognosis of GC patients is still unclear. AIM: To investigate inflammatory-related biomarkers in predicting the prognosis of GC patients. METHODS: In this study, the mRNA expression profiles and corresponding clinical information of GC patients were obtained from the Gene Expression Omnibus (GEO) database (GSE66229). An inflammatory-related gene prognostic signature model was constructed using the least absolute shrinkage and selection operator Cox regression model based on the GEO database. GC patients from the GSE26253 cohort were used for validation. Univariate and multivariate Cox analyses were used to determine the independent prognostic factors, and a prognostic nomogram was established. The calibration curve and the area under the curve based on receiver operating characteristic analysis were utilized to evaluate the predictive value of the nomogram. The decision curve analysis results were plotted to quantify and assess the clinical value of the nomogram. Gene set enrichment analysis was performed to explore the potential regulatory pathways involved. The relationship between tumour immune infiltration status and risk score was analysed via Tumour Immune Estimation Resource and CIBERSORT. Finally, we analysed the association between risk score and patient sensitivity to commonly used chemotherapy and targeted therapy agents. RESULTS: A prognostic model consisting of three inflammatory-related genes (MRPS17, GUF1, and PDK4) was constructed. Independent prognostic analysis revealed that the risk score was a separate prognostic factor in GC patients. According to the risk score, GC patients were stratified into high- and low-risk groups, and patients in the high-risk group had significantly worse prognoses according to age, sex, TNM stage and Lauren type. Consensus clustering identified three subtypes of inflammation that could predict GC prognosis more accurately than traditional grading and staging. Finally, the study revealed that patients in the low-risk group were more sensitive to certain drugs than were those in the high-risk group, indicating a link between inflammation-related genes and drug sensitivity. CONCLUSION: In conclusion, we established a novel three-gene prognostic signature that may be useful for predicting the prognosis and personalizing treatment decisions of GC patients.

15.
Sci Total Environ ; 929: 172622, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38642761

RESUMO

The phyllosphere is a vital yet often neglected habitat hosting diverse microorganisms with various functions. However, studies regarding how the composition and functions of the phyllosphere microbiome respond to agricultural practices, like nitrogen fertilization, are limited. This study investigated the effects of long-term nitrogen fertilization with different levels (CK, N90, N210, N330) on the functional genes and pathogens of the rice phyllosphere microbiome. Results showed that the relative abundance of many microbial functional genes in the rice phyllosphere was significantly affected by nitrogen fertilization, especially those involved in C fixation and denitrification genes. Different nitrogen fertilization levels have greater effects on fungal communities than bacteria communities in the rice phyllosphere, and network analysis and structural equation models further elucidate that fungal communities not only changed bacterial-fungal inter-kingdom interactions in the phyllosphere but also contributed to the variation of biogeochemical cycle potential. Besides, the moderate nitrogen fertilization level (N210) was associated with an enrichment of beneficial microbes in the phyllosphere, while also resulting in the lowest abundance of pathogenic fungi (1.14 %). In contrast, the highest abundance of pathogenic fungi (1.64 %) was observed in the highest nitrogen fertilization level (N330). This enrichment of pathogen due to high nitrogen level was also regulated by the fungal communities, as revealed through SEM analysis. Together, we demonstrated that the phyllosphere fungal communities were more sensitive to the nitrogen fertilization levels and played a crucial role in influencing phyllosphere functional profiles including element cycling potential and pathogen abundance. This study expands our knowledge regarding the role of phyllosphere fungal communities in modulating the element cycling and plant health in sustainable agriculture.


Assuntos
Fertilizantes , Fungos , Nitrogênio , Oryza , Oryza/microbiologia , Fungos/fisiologia , Micobioma , Agricultura , Microbiota , Folhas de Planta/microbiologia
16.
Biomed Pharmacother ; 175: 116519, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38663104

RESUMO

OBJECTIVES: To elucidate the therapeutic effects and mechanisms of Atractylodes macrocephala extract crystallize (BZEP) and BZEP self-microemulsion (BZEPWR) on metabolic dysfunction-associated fatty liver disease (MAFLD) induced by "high sugar, high fat, and excessive alcohol consumption" based on the gut-liver axis HDL/LPS signaling pathway. METHODS: In this study, BZEP and BZEPWR were obtained via isolation, purification, and microemulsification. Furthermore, an anthropomorphic MAFLD rat model of "high sugar, high fat, and excessive alcohol consumption" was established. The therapeutic effects of BZEPWR and BZEP on the model rats were evaluated in terms of liver function, lipid metabolism (especially HDL-C), serum antioxidant indexes, and liver and intestinal pathophysiology. To determine the lipoproteins in the serum sample, the amplitudes of a plurality of NMR spectra were derived via deconvolution of the composite methyl signal envelope to yield HDL-C subclass concentrations. The changes in intestinal flora were detected via 16 S rRNA gene sequencing. In addition, the gut-liver axis HDL/LPS signaling pathway was validated using immunohistochemistry, immunofluorescence, and western blot. RESULTS: The findings established that BZEPWR and BZEP improved animal signs, serum levels of liver enzymes (ALT and AST), lipid metabolism (TC, TG, HDL-C, and LDL-C), and antioxidant indexes (GSH, SOD, and ROS). In addition, pathological damage to the liver, colon, and ileum was ameliorated, and the intestinal barrier function of the model rats was restored. At the genus level, BZEPWR and BZEP exerted positive effects on beneficial bacteria, such as Lactobacillus and norank_f__Muribaculaceae, and inhibitory effects on harmful bacteria, such as unclassified_f__Lachnospiraceae and Blautia. Twenty HDL-C subspecies were detected, and their levels were differentially increased in both BZEPWR and BZEP groups, with BZEPWR exhibiting a stronger elevating effect on specific HDL-C subspecies. Also, the gut-liver axis HDL/LPS signaling pathway was studied, which indicated that BZEPWR and BZEP significantly increased the expressions of ABCA1, LXR, occludin, and claudin-1 proteins in the gut and serum levels of HDL-C. Concomitantly, the levels of LPS in the serum and TLR4, Myd88, and NF-κB proteins in the liver were decreased. CONCLUSION: BZEPWR and BZEP exert restorative and reversal effects on the pathophysiological damage to the gut-liver axis in MAFLD rats, and the therapeutic mechanism may be related to the regulation of the intestinal flora and the HDL/LPS signaling pathway.


Assuntos
Atractylodes , Emulsões , Microbioma Gastrointestinal , Lipopolissacarídeos , Fígado , Extratos Vegetais , Ratos Sprague-Dawley , Transdução de Sinais , Animais , Transdução de Sinais/efeitos dos fármacos , Masculino , Ratos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Atractylodes/química , Extratos Vegetais/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Lipoproteínas HDL/sangue , Modelos Animais de Doenças , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado Gorduroso/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Antioxidantes/farmacologia
17.
Small ; 20(24): e2311811, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38372500

RESUMO

Amid growing interest in using body heat for electricity in wearables, creating stretchable devices poses a major challenge. Herein, a hydrogel composed of two core constituents, namely the negatively-charged 2-acrylamido-2-methylpropanesulfonic acid and the zwitterionic (ZI) sulfobetaine acrylamide, is engineered into a double-network hydrogel. This results in a significant enhancement in mechanical properties, with tensile stress and strain of up to 470.3 kPa and 106.6%, respectively. Moreover, the ZI nature of the polymer enables the fabrication of a device with polar thermoelectric properties by modulating the pH. Thus, the ionic Seebeck coefficient (Si) of the ZI hydrogel ranges from -32.6 to 31.7 mV K-1 as the pH is varied from 1 to 14, giving substantial figure of merit (ZTi) values of 3.8 and 3.6, respectively. Moreover, a prototype stretchable ionic thermoelectric supercapacitor incorporating the ZI hydrogel exhibits notable power densities of 1.8 and 0.9 mW m-2 at pH 1 and 14, respectively. Thus, the present work paves the way for the utilization of pH-sensitive, stretchable ZI hydrogels for thermoelectric applications, with a specific focus on harvesting low-grade waste heat within the temperature range of 25-40 °C.

18.
Lab Anim Res ; 40(1): 4, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38355576

RESUMO

Phytoestrogens, such as isoflavones, are known for their capacity to simulate various physiological impacts of estrogen in the human body. Our research evaluated the effects of isoflavone-enriched soybean leaves (IESL) on collagen fiber loss prompted by ovariectomy in Sprague Dawley (SD) rats, thereby simulating menopausal changes in women. IESL, bolstered with an increased concentration of isoflavones through a metabolite farming process, contained a significantly higher amount of isoflavones than regular soybean leaves. Our results indicate that the administration of IESL can counteract the decrease in relative optical density and dermal thickness of collagen fibers caused by ovariectomy in SD rats, with more pronounced effects observed at higher isoflavone dosages. These outcomes suggest that soybean leaves rich in isoflavones may hold potential benefits in combating collagen degradation and skin aging symptoms related to menopause. Further research is needed to fully understand the exact molecular pathways at play and the potential clinical relevance of these findings.

19.
ACS Appl Mater Interfaces ; 16(6): 7500-7511, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38300744

RESUMO

In recent years, organic photonic field-effect transistors have made remarkable progress with the rapid development of conjugated polycrystalline materials. Liquid crystals, with their smooth surface, defined layer thickness, and crystalline structures, are commonly used for these advantages. In this work, a series of smectic liquid crystalline molecules, 2,9-didecyl-dinaphtho-thienothiophene (C10-DNTT), 2,7-didecyl-benzothieno-benzothiopene (C10-BTBT), 3,9-didecyl-dinaphtho-thiophene (C10-DNT), and didecyl-sexithiophene (C10-6T), have been used in photonic transistor memory, functioning as both hole-transport channels and electron traps to investigate systematically the reasons and mechanisms behind the memory behavior of smectic liquid crystals. After thermal annealing, C10-BTBT and C10-6T/C10-DNTT are homeotropically aligned from the smectic A and smectic X phases, respectively. The 3D-ordered structure of these smectic-aligned crystals contributed to efficient photowriting and electrical erasing processes. Among them, the device performance of C10-BTBT was particularly significant, with a memory window of 21 V. The memory ratio could reach 1.5 × 106 and maintain a memory ratio of over 3 orders after 10,000 s, contributing to its smectic A structure. Through the research, we confirmed the memory and light/bias-gated behaviors of these smectic liquid crystalline molecules, attributing them to reversible molecular conformation transitions and the inherent structural inhomogeneity inside the polycrystalline channel layer.

20.
Ecotoxicol Environ Saf ; 272: 116075, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38325273

RESUMO

Although animal studies have shown the reproductive toxicity of vanadium, less is known about its effects on semen quality in humans. Among 1135 healthy men who were screened as potential semen donors, we investigated the relationships of semen quality with urinary and seminal plasma vanadium levels via inductively coupled plasma-mass spectrometry (ICP-MS). Spearman rank correlation tests and linear regression models were used to assess the correlations between average urinary and within-individual pooled seminal plasma vanadium concentrations (n = 1135). We utilized linear mixed-effects models to evaluate the associations of urinary and seminal plasma vanadium levels (n = 1135) with repeated sperm quality parameters (n = 5576). Seminal plasma vanadium concentrations were not significantly correlated with urinary vanadium concentrations (r = 0.03). After adjusting for possible confounders, we observed inverse relationships of within-individual pooled seminal plasma vanadium levels with total count, semen volume, and sperm concentration (all P values for trend < 0.05). Specifically, subjects in the highest (vs. lowest) tertile of seminal plasma vanadium concentrations had - 11.3% (-16.4%, -5.9%), - 11.1% (-19.1%, -2.4%), and - 20.9% (-29.0%, -11.8%) lower sperm volume, concentration, and total count, respectively; moreover, urinary vanadium levels appeared to be negatively associated with sperm motility. These relationships showed monotonically decreasing dose-response patterns in the restricted cubic spline analyses. Our results demonstrated a poor correlation between urinary and seminal plasma levels of vanadium, and elevated vanadium concentrations in urine and seminal plasma may be adversely related to male semen quality.


Assuntos
Análise do Sêmen , Sêmen , Animais , Masculino , Humanos , Sêmen/química , Vanádio/toxicidade , Vanádio/análise , Motilidade dos Espermatozoides , Contagem de Espermatozoides , Espermatozoides/fisiologia
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