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1.
J Colloid Interface Sci ; 677(Pt B): 140-150, 2025 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-39142155

RESUMO

The explorations of efficient electrocatalysts to accelerate oxygen reactions in a wide temperature range is a crucial issue to the development of zinc-air batteries (ZAB) for all-climate applications. Herein, the Co-CoSe heterogeneous furry fibers (Co-CoSe@NHF) are developed as a bifunctional oxygen electrocatalyst for ZAB towards wide-temperature range applications. The Co-CoSe heterostructure with large work function difference (ΔWF) endows interfacial electron redistribution, which builds strong interfacial built-in electric field (BIEF) and improves the oxygen reactions. Meanwhile, the Co-CoSe heterostructure is encapsulated by in-situ grown carbon nanotubes, and forms the hollow fiber (NHF) with furry surface and beads-on-string configuration. The highly porous and conductive NHF configuration facilitates the fast kinetics and favors to accommodates volume change during cycling. As a result, the Co-CoSe@NHF achieves the superior bifunctional properties and good reliability for oxygen reactions. Integrated with the Co-CoSe@NHF fiber, the ZAB cell delivers the superior power density (301 mW cm-2) and long-term cycling stability over 280 h at 25 °C, and maintains the power densities of 126 mW cm-2 even the temperature decreases to -25 °C. Moreover, the solid-state ZAB exhibits significant flexibility and superior properties in a wide temperature range. Therefore, this work not only proposes a new strategy to design the high-performance bifunctional electrocatalysts, but also propels the development of flexible power sources for all-climate applications.

2.
Front Immunol ; 15: 1425585, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39483465

RESUMO

Background: The differentiation of hematopoietic cells is significantly affected by cell metabolic activity. However, despite increasing interest in this field, there has been no comprehensive investigation of the metabolic functions of human hematopoietic cells during specific phases of differentiation. Thus, this study was conducted to develop a method for comparing hematopoietic cell lineage differentiation based on the metabolic functions of the cell. The metabolic activity of human umbilical cord-derived hematopoietic cells was examined during various phases of differentiation, specifically, hematopoietic stem cells (HSCs), hematopoietic progenitor cells, and differentiated blood cells. This approach was used to develop comprehensive metabolic maps corresponding to the different stages. Results: HSCs were found to have robust fatty acid (FA) synthesis, FA oxidation, pentose phosphate pathway (PPP) activity, and glucose uptake, shown by their significantly higher expression of ACAC, CPT1A, G6PD, and GLUT1 as compared to differentiated pluripotent progenitor cells, common myeloid progenitors, megakaryocyte erythroid progenitors, lympho-myeloid primed progenitors, and granulocyte-macrophage progenitor cell populations. In monocytic differentiation, higher levels of ACAC, ASS1, ATP5A, CPT1A, G6PD, GLUT1, IDH2, PRDX2, and HK1 protein expression were evident in classical and intermediate monocytes relative to non-classical monocytes, consistent with high anabolic and catabolic levels. Compared with myelocytes and mature cells, the meta-myelocyte and pro-myelocyte populations of granulocytes show significantly elevated levels of ACAC, ASS1, ATP5A, CPT1A, G6PD, IDH2, PRDX2, and HK. In contrast to naïve and regulatory B cells, pro-B cells had higher levels of oxidative phosphorylation, while regulatory B cells showed greater PPP activity, glucose uptake, and tricarboxylic acid cycle activity. The analyses of T cells also indicated significantly higher ACAC, ASS1, ATP5A, CPT1A, G6PD, GLUT1, IDH2, PRDX2, and HK1 expression levels in CD4+ populations compared with CD8+ populations. Conclusions: The results provide comprehensive analytical methods and reference values for future systematic studies into the metabolic functions of various cord blood-derived hematopoietic cell populations in different pathological or physiological conditions. These findings could also contribute to research on the connection between cellular metabolism and cancer or aging.


Assuntos
Diferenciação Celular , Sangue Fetal , Células-Tronco Hematopoéticas , Humanos , Sangue Fetal/citologia , Células-Tronco Hematopoéticas/metabolismo , Células-Tronco Hematopoéticas/citologia , Citometria de Fluxo , Ácidos Graxos/metabolismo , Células Cultivadas
3.
Environ Microbiome ; 19(1): 83, 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-39487540

RESUMO

BACKGROUND: Tobacco production faces ongoing challenges due to soil degradation, leading to a persistent decline in yield. Plant growth-promoting fungi (PGPF) have been recognized as an environmentally friendly agricultural strategy. However, many commercial PGPF products exhibit instability due to insufficient environmental compatibility. RESULTS: In this study, Penicillium sp. PQxj3 was isolated and assessed for its potential to enhance tobacco productivity under field conditions. The results demonstrated that Penicillium sp. PQxj3 treatment significantly promoted the tobacco growth and improved the crop yield. The height of tobacco in Penicillium sp. PQxj3 treatment group significantly increased by 50.19% and 24.05% compared with CK at exuberant and maturity period (P < 0.05). The average yield of tobacco significantly increased by 36.16% compared to CK (P < 0.05). Fungal microbiome analysis revealed that phylogenetically similar probiotic taxa were recruited by Penicillium sp. PQxj3 and reassembled tobacco rhizosphere fungal microbiome. The key chemical indicators of tobacco such as alkaloid, total sugar, and phosphorus were significantly enhanced in Penicillium sp. PQxj3 treatment. The recruited probiotic taxa (Penicillium brasilianum, Penicillium simplicissimum, Penicillium macrosclerotiorum and Penicillium senticosum) were significantly associated with alkaloid, total sugar etc. (P < 0.05), which were identified as the key drivers for improving the chemical components of tobacco. Transcriptome analysis indicated that Penicillium sp. PQxj3 promoted up-regulation of key functional genes involved in alkaloid, indoleacetic, and gibberellin biosynthesis pathways. CONCLUSION: In summary, this study assessed the biopromotion mechanism of PGPF Penicillium sp. PQxj3 linking chemical traits, rhizosphere fungal microbiome, and transcriptome profiling. The findings provide a fundamental basis and a sustainable solution for developing fungal fertilizers to enhance agricultural sustainability.

4.
Int J Biol Sci ; 20(14): 5548-5575, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39494327

RESUMO

Background: Tumor progression and limited benefits of immune checkpoint blockade (ICB) therapy have been two major challenges in the clinical management of colorectal cancer (CRC). The objective of our research was to explore the role of PLCG2 in CRC progression, tumor microenvironment, and potentiating ICB therapy. Methods: Based on bioinformatics analysis and a prospective clinical observational study, the expression, prognostic significance, and clinical relevance of PLCG2 in CRC were unveiled. The single-cell and spatial transcriptome revealed the role of PLCG2 in shaping the heterogeneity of the CRC tumor microenvironment. The biological function of PLCG2 was validated by in vivo and in vitro experiments. The underlying mechanisms were elucidated by RNA-seq, western blotting, qRT-PCR, and multicolor immunofluorescence. The multiplex immunohistochemistry and flow cytometry were adopted to clarify the immunomodulatory role of PLCG2 in facilitating CRC immune escape. The translational value of targeting PLCG2 to potentiate the efficacy of ICB therapy and synergistic therapy to improve prognosis was explored in the preclinical animal models. Results: In CRC, PLCG2 exhibited high expression levels and was strongly associated with poor prognosis and advanced clinicopathological characteristics of patients. The single-cell transcriptome shed light on its important role in cell communication and the development and differentiation of immune cells. The spatial transcriptome described the spatial distribution of PLCG2 in CRC tissues. Further mechanistic analysis demonstrated that PLCG2 could promote proliferation, invasion, metastasis, epithelial-mesenchymal transition, and cell cycle regulation and inhibit apoptosis of CRC cells via the Akt-mTOR pathway activation. Furthermore, PLCG2 was found to contribute greatly to the immunosuppressive microenvironment and enhanced immune escape as it significantly suppressed the infiltration and functional activation of CD8+ T cells and promoted the infiltration of Treg cells as well as PD-1 and PD-L1 expression. Meanwhile, knockdown of PLCG2 could potentiate the efficacy of ICB therapy. Conclusion: In summary, we have identified for the first time that PLCG2 could be considered a precise biomarker and promising therapeutic target for predicting CRC prognosis, optimizing individualized treatment, reversing CRC immune escape, and overcoming resistance to ICB therapy.


Assuntos
Neoplasias Colorretais , Inibidores de Checkpoint Imunológico , Microambiente Tumoral , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/imunologia , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Animais , Camundongos , Linhagem Celular Tumoral , Masculino , Feminino , Prognóstico , Progressão da Doença
5.
J Colloid Interface Sci ; 679(Pt B): 947-956, 2024 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-39486233

RESUMO

The design of highly efficient catalysts to enhance the kinetics of oxygen reduction (OER) and oxygen evolution (ORR) reactions is the key issue for the development of high-performance Zn-air battery. In this work, we report the design of Co-CoTe heterostructured fibers as the bifunctional oxygen catalyst for Zn-air battery. Firstly, the theoretical analysis was carried out on Co-CoTe heterostructure. The large work function difference is favorable to construct strong interfacial built-in electric field (BIEF), and the low energy barrier endows high catalytic activities. Moreover, the in-situ grown carbon shell was designed to build "core-shell" Co-CoTe/C unit to realize its high performance. They assemble the Co-CoTe@HFS fiber with good self-supporting and flexible features. Taken the advantages of the strong BIEF, the "core-shell" basic unit, and the freestanding substrate, the Co-CoTe@HFS fiber achieves the good electrocatalytic properties and high reliability. The full Zn-air battery (ZAB) with the Co/CoTe@HFS air cathode achieves the high peak power density and cycling stability over long-term cycling. Therefore, this work provides a clue to design bifunctional oxygen catalysts for high-performance ZABs.

6.
Int J Biol Macromol ; : 137109, 2024 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-39486694

RESUMO

Despite the remarkable potential of phase change fibers for energy storage, their practical deployment has been hindered by two crucial challenges: inadequate external thermal stimulation to induce phase transition and leakage of the phase-change material. In this study, we successfully incorporated carbon nanotubes (CNTs) into a solution of sodium alginate grafted polyethylene glycol monomethyl ether (SA-g-mPEG) and utilized wet spinning processing to fabricate CNTs/SA-g-mPEG hybrid fibers with enhanced photo-thermal conversion and robust solid-solid phase change capabilities. Upon exposure to sunlight for merely 60 s, the hybrid fibers achieved a remarkable peak temperature of 40 °C. Upon cessation of sunlight exposure, these fibers demonstrated a gradual release of thermal energy, thereby underlining their exceptional photothermal conversion and temperature regulation capabilities. Furthermore, DSC analysis revealed that, at an optimal grafting ratio of 36.6 %, the hybrid fibers exhibited ΔHc and ΔHm values of 48.23 J/g and 50.83 J/g, respectively. Notably, hybrid fibers with a grafting ratio of 20.2 % demonstrated substantial enhancements in tensile properties, achieving a maximum breaking strength of approximately 2.02 cN/dtex-an impressive 11.3 % increase compared to SA-g-mPEG composite fibers. Our findings suggest that CNTs/SA-g-mPEG hybrid fibers hold immense promise for applications in body heat storage, fabric temperature regulation, and related fields.

7.
Front Mol Neurosci ; 17: 1406708, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39359688

RESUMO

The Monoamine Oxidase-A (MAOA) EcoRV polymorphism (rs1137070) is a unique synonymous mutation (c.1409 T > C) within the MAOA gene, which plays a crucial role in Maoa gene expression and function. This study aimed to explore the relationship between the mouse Maoa rs1137070 genotype and differences in MAOA gene expression. Mice carrying the CC genotype of rs1137070 exhibited a significantly lower Maoa expression level, with an odds ratio of 2.44 compared to the T carriers. Moreover, the wild-type TT genotype of MAOA demonstrated elevated mRNA expression and a longer half-life. We also delved into the significant expression and structural disparities among genotypes. Furthermore, it was evident that different aspartic acid synonymous codons within Maoa influenced both MAOA expression and enzyme activity, highlighting the association between rs1137070 and MAOA. To substantiate these findings, a dual-luciferase reporter assay confirmed that GAC was more efficient than GAT binding. Conversely, the synonymous mutation altered Maoa gene expression in individual mice. An RNA pull-down assay suggested that this alteration could impact the interaction with RNA-binding proteins. In summary, our results illustrate that synonymous mutations can indeed regulate the downregulation of gene expression, leading to changes in MAOA function and their potential association with neurological-related diseases.

8.
Rev Sci Instrum ; 95(10)2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39392343

RESUMO

A two-color homodyne Mach-Zehnder optical fiber interferometer is developed for the measurement of electron and neutral particle densities in a high-density capsule θ-pinch device. The interferometer leverages the disparate contributions of distinct particles to the refractive index across two discrete wavelengths of 1310 and 1550 nm and incorporates the contributions of both electron and neutral particle densities to the phase shift in the plasma. The temporal evolutions of line-integrated electron and neutral argon densities are successfully measured by the interferometer. Comparing the electron density waveforms under various working gas pressures as well as the results obtained using the monochromatic and two-color measurements, it is inferred that the influence of neutral particle density can be neglected when measuring the electron density using a long-wavelength laser. Moreover, the maximum electron density is linearly correlated with the capacitor bank voltage for the θ-pinch device (5-9 kV). Overall, the proposed interferometer is capable of simultaneously measuring the electron and neutral particle densities.

9.
Nanomaterials (Basel) ; 14(20)2024 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-39452974

RESUMO

Two-dimensional (2D) ferroelectrics usually exhibit instability or a tendency toward degradation when exposed to the ambient atmosphere, and the mechanism behind this phenomenon remains unclear. To unravel this affection mechanism, we have undertaken an investigation utilizing NH3 and two-dimensional ferroelectric SnS. Herein, the adsorption and desorption of NH3 molecules can reversibly modulate the electrical properties of SnS, encompassing I-V curves and transfer curves. The response time for NH3 adsorption is approximately 1.12 s, which is much quicker than that observed in other two-dimensional materials. KPFM characterizations indicate that air molecules' adsorption alters the surface potentials of SiO2, SnS, metal electrodes, and contacts with minimal impact on the electrode contact surface potential. Upon the adsorption of NH3 molecules or air molecules, the hole concentration within the device decreases. These findings elucidate the adsorption mechanism of NH3 molecules on SnS, potentially fostering the advancement of rapid gas sensing applications utilizing two-dimensional ferroelectrics.

10.
Huan Jing Ke Xue ; 45(10): 6171-6184, 2024 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-39455160

RESUMO

Considering the surface soil (0-20 cm) from a typical abandoned antimony smelting factory area in Dachang Town, Qinglong County, Guizhou Province, as a case study, a total of 14 soil samples were systematically collected from both within and outside the smelting factory area. The analysis focused on the pollution status, distribution characteristics, and potential ecological risks of heavy metals such as Sb, As, Cd, Cr, Pb, Cu, Zn, Ni, and V in the soil. Additionally, an evaluation and analysis of pollution sources were conducted. The results showed that the mean concentrations of heavy metals including ω(Sb), ω(As), ω(Cd), ω(Cr), ω(Pb), ω(Cu), ω(Zn), ω(Ni), and ω(V) in the surface soil of the abandoned antimony smelting factory ranged from 4.58 to 15 049.33 mg·kg-1. With the exception of Cr and Ni, all values exceeded the background values of soils in Guizhou province. The single factor pollution indices of Sb and As were 83.61 and 7.01, respectively, indicating severe contamination. In contrast, Pb fell within the non-polluted to slightly polluted range. The comprehensive potential ecological risk of soil heavy metals was characterized by severe potential ecological risk levels for Sb, As, and Cd, while the remaining heavy metals fell within a range of moderate to substantial potential ecological risk levels. The assessment of the geoaccumulation index revealed that the soil in the study area was primarily contaminated by Sb and As, predominantly exhibiting contamination levels ranging from moderate to severe. The results from the RAC method suggested that Sb was the dominant focus for remediation in this abandoned smelting factory. The two primary pollutants, Sb and As, exhibited elevated levels in leachate toxicity, acid-soluble fraction, available fraction, gastric phase, and intestinal phase in terms of bioavailable content, indicating a certain potential hazard. Further, correlation analysis indicated a certain correlation between the total amount of heavy metals and leachate toxicity, available fraction, acid-soluble fraction, reducible fraction, oxidizable fraction, gastric phase extractable fraction, and intestinal phase extractable fraction. The APCS-MLR model indicated that the sources of Sb, As, Zn, Cu, and Cd were primarily industrial, while the sources of Cr and V were mainly natural, and Pb originated mainly from mixed sources.


Assuntos
Antimônio , Monitoramento Ambiental , Metais Pesados , Poluentes do Solo , Metais Pesados/análise , Poluentes do Solo/análise , Antimônio/análise , China , Medição de Risco , Metalurgia , Solo/química , Arsênio/análise
11.
Free Radic Biol Med ; 225: 560-580, 2024 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-39368519

RESUMO

Cumulative evidence has verified that persistent oxidative stress is involved in the development of various chronic diseases, including pulmonary, neurodegenerative, kidney, cardiovascular, and liver diseases, as well as cancers. Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a pivotal role in regulating cellular oxidative stress and inflammatory reactions, making it a focal point for disease prevention and treatment strategies. Natural products are essential resources for discovering leading molecules for new drug research and development. In this review, we comprehensively outlined the progression of the knowledge on the Nrf2 pathway, Nrf2 activators in clinical trials, the naturally-derived Nrf2 modulators (particularly from 2014-present), as well as their effects on the pathogenesis of chronic diseases.

12.
Nat Commun ; 15(1): 8808, 2024 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-39394203

RESUMO

Cryo-electron microscopy (cryo-EM) technique is widely used for protein structure determination. Current automatic cryo-EM protein complex modeling methods mostly rely on prior chain separation. However, chain separation without sequence guidance often suffers from errors caused by cross-chain interaction or noise densities, which would accumulate and mislead the subsequent steps. Here, we present EModelX, a fully automated cryo-EM protein complex structure modeling method, which achieves sequence-guiding modeling through cross-modal alignments between cryo-EM maps and protein sequences. EModelX first employs multi-task deep learning to predict Cα atoms, backbone atoms, and amino acid types from cryo-EM maps, which is subsequently used to sample Cα traces with amino acid profiles. The profiles are then aligned with protein sequences to obtain initial structural models, which yielded an average RMSD of 1.17 Å in our test set, approaching atomic-level precision in recovering PDB-deposited structures. After filling unmodeled gaps through sequence-guiding Cα threading, the final models achieved an average TM-score of 0.808, outperforming the state-of-the-art method. The further combination with AlphaFold can improve the average TM-score to 0.911. Analyzes conducted by comparing some EModelX-built models and PDB structures highlight its potential to improve PDB structures. EModelX is accessible at https://bio-web1.nscc-gz.cn/app/EModelX .


Assuntos
Microscopia Crioeletrônica , Modelos Moleculares , Conformação Proteica , Proteínas , Microscopia Crioeletrônica/métodos , Proteínas/química , Proteínas/ultraestrutura , Software , Aprendizado Profundo , Sequência de Aminoácidos , Algoritmos , Alinhamento de Sequência/métodos
13.
Org Lett ; 26(43): 9203-9209, 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-39431996

RESUMO

Controlling the selectivity of reactions is a significantly attractive strategy in synthetic organic chemistry. Herein, an efficient base-controlled chemodivergent domino reaction between o-aminochalcones and γ-bromocrotonates has been developed. A series of cis-2,3-disubstituted indolines and cyclopropane-fused tetrahydroquinolines were obtained via two pathways with a broad substrate scope in moderate to excellent yields under transition-metal-free conditions. It is noteworthy that the γ-bromocrotonates could be used as C1 or C2 synthons by modulating the base; in particular, the γ-bromocrotonates were used as both nucleophiles and electrophiles to generate cyclopropanes for the first time.

14.
Sci Rep ; 14(1): 24789, 2024 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-39433560

RESUMO

Evidence shows that inflammatory responses play an essential role in the development of brain metastases (BM). The goal of this meta-analysis was to critically evaluate the literature regarding the use of the neutrophil to lymphocyte ratio (NLR) to predict the prognosis of patients with BM to help clinicians institute early interventions and improve outcomes. We conducted systematic review and meta-analysis, utilizing data from prominent databases, including PubMed, Cochrane Library and China National Knowledge Infrastructure databases. Our inclusion criteria encompassed studies investigating the studies that assessed the association between NLR and overall survival (OS). We included 11 articles, with 2629 eligible patients, to evaluate the association between NLR and OS. High NLR was significantly associated with shorter OS, with a pooled hazard ratio (HR) of 1.82 (95% CI 1.57-2.11). Subgroup analysis revealed that this association was consistent across different regions, with HRs of 2.03 (95% CI 1.67-2.46) in Asian populations and 1.58 (95% CI 1.35-1.84) in non-Asian populations. Additionally, in a subgroup analysis based on NLR cut-off values, patients with NLR ≥ 3 had an HR of 1.69 (95% CI 1.46-1.96), while those with NLR < 3 had an HR of 2.26 (95% CI 1.64-3.11). Sensitivity analysis confirmed that no single study significantly influenced the pooled effect size. Our meta-analysis confirmed the prognostic value of NLR in patients with brain metastasis.


Assuntos
Neoplasias Encefálicas , Linfócitos , Neutrófilos , Humanos , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/sangue , Neoplasias Encefálicas/mortalidade , Prognóstico , Contagem de Linfócitos
15.
Life Sci ; 357: 123080, 2024 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-39332486

RESUMO

OBJECTIVE: Endogenous glucocorticoid levels display a strong circadian rhythm, which is often not considered when synthetic glucocorticoids are prescribed as anti-inflammatory drugs. In this study we evaluated the effect timing of glucocorticoid administration, i.e. in-phase (administered when endogenous glucocorticoid levels are high) versus out-of-phase (administered when endogenous glucocorticoid levels are low). We investigated the synthetic glucocorticoid betamethasone - which is extensively used in the clinic - and monitored the development of common metabolic side effects in mice upon prolonged treatment, with a particular focus on glucose metabolism. METHODS: Male and female C57BL/6J mice were treated with the synthetic glucocorticoid betamethasone in-phase and out-of-phase, and the development of metabolic side effects was monitored. RESULTS: We observed that, compared with in-phase treatment, out-of-phase treatment with betamethasone results in hyperinsulinemia in both male and female C57BL/6J mice. We additionally found that out-of-phase betamethasone treatment strongly reduced insulin sensitivity as compared to in-phase administration during morning measurements. Our study shows that the adverse effects of betamethasone are dependent on the time of treatment with generally less side effects on glucose metabolism with in-phase treatment. CONCLUSIONS: This study highlights differences in glucocorticoid outcome based on the time of measurement, advocating that potential circadian variation should be taken into account when studying glucocorticoid biology.


Assuntos
Betametasona , Ritmo Circadiano , Glucocorticoides , Glucose , Camundongos Endogâmicos C57BL , Animais , Betametasona/farmacologia , Feminino , Masculino , Glucocorticoides/farmacologia , Camundongos , Ritmo Circadiano/efeitos dos fármacos , Glucose/metabolismo , Resistência à Insulina , Glicemia/metabolismo , Glicemia/efeitos dos fármacos
16.
Brain Res Bull ; 217: 111076, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39306046

RESUMO

In recent years, overwhelming evidence has emphasized the crucial role of inflammation in the pathogenesis of PD. However, the exact mechanisms by which inflammation damages dopaminergic neurons in PD are still unclear. Therefore, we generated a MPTP-induced PD mouse model and performed spatial transcriptomic sequencing to provide more insight into the process of PD development at specific brain regions. Our results indicate that the pathological changes of PD are mainly manifested in the midbrain, especially in the substantia nigra region, with significant reductions in oligodendrocytes and Agt-labeled astrocytes and an increase in Gfap-labeled astrocytes. Macrophages displayed an increasing trend in the PD environment, indicating a pattern of immune modulation induced by PD. Moreover, pathway analysis revealed significant impairments in ion migration ability, abnormal Ca2+ channels, cAMP signaling, and synaptic damage in PD. Significant downregulation of Mt1 and Mt2 and upregulation of Atp1b2, Gpi1, and Cox6a1 in PD further underscored the occurrence of intense inflammation and immune alterations. On the basis of these findings, we have validated the significant accumulation of Ca2+ in the midbrain tissue in the PD environment by measuring its content. Additionally, we have demonstrated a close association between the reduction of dopaminergic neurons, represented by the midbrain region, and ferroptosis by evaluating the iron content, malondialdehyde (MDA) levels, and the protein expression of GPX4 and TH in the tissue. We propose the hypothesis that PD-related inflammation and immune changes can induce neuronal and oligodendrocyte damage through the induction of ferroptosis, thereby further accelerating the progression of PD.


Assuntos
Neurônios Dopaminérgicos , Inflamação , Camundongos Endogâmicos C57BL , Animais , Camundongos , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/patologia , Inflamação/metabolismo , Masculino , Doença de Parkinson/metabolismo , Doença de Parkinson/genética , Doença de Parkinson/imunologia , Doença de Parkinson/patologia , Transcriptoma , Substância Negra/metabolismo , Substância Negra/patologia , Mesencéfalo/metabolismo , Mesencéfalo/patologia , Astrócitos/metabolismo , Modelos Animais de Doenças , Doenças Neuroinflamatórias/metabolismo , Macrófagos/metabolismo , Macrófagos/imunologia , Perfilação da Expressão Gênica/métodos
17.
Br J Ophthalmol ; 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39227133

RESUMO

BACKGROUND: To assess predictive value of short-term choroidal changes for future myopic shift in children. METHODS: 577 eyes of 289 primary school children were prospectively followed for 2 years. Cycloplegic refractions at baseline, 1 year and 2 years, and choroidal measurements by optical coherence tomography at baseline and 3 months, were used for analyses. Myopic shift was defined as refraction change of at least -0.50 dioptre/year, at 2 years compared with baseline. RESULTS: 228 participants (455 eyes) completed 2-year follow-up. Approximately 37.6% of 311 initially non-myopic eyes and 73.6% of 144 initially myopic eyes developed a myopic shift. Notably, at 3 months greater reductions were found in initially myopic eyes with myopic shift, than in those without myopic shift-in choroidal thickness (ChT), luminal area (LA), stromal area (SA) and total choroidal area (TCA), but no significant differences in any choroidal parameters were observed between non-myopic eyes, with and without myopic shift. Multivariable analyses showed that in myopic eyes, each percentage increase in ChT, LA, SA and TCA was associated with reduced odds of myopic shift (all p<0.001). Similar associations were observed in non-myopic eyes, with smaller effects than in myopic eyes. Adding a 3-month percentage change of each choroidal parameter to a basic model including age, gender, parental myopia and baseline refraction significantly improved the predictive performance in myopic eyes (area under the receiver operating characteristic curves increasing from 0.650 to approximately 0.800, all p<0.05), but not in non-myopic eyes. CONCLUSION: Short-term choroidal changes could act as early indicators for future myopic shift in children.

18.
J Phys Chem Lett ; 15(36): 9301-9310, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39235319

RESUMO

The development of monolithic integrated energy-efficient complementary circuits is crucial for the large-scale application of wide bandgap semiconductor-based high-frequency and high-power field-effect transistors (FETs). However, the inferior performance of p-channel FETs attributed to low hole density and mobility presents a substantial challenge. Diamond is a promising candidate due to its excellent comprehensive electrical properties and high thermal conductivity. Here, we report the fabrication of normally off diamond FETs based on a low work function metal gate and (110) hydrogen-terminated diamond with high hole density. The use of high-quality SiO2 layer ensures the complete depletion of the channel by the gate and offers high gating efficiency. Therefore, the developed devices demonstrate exceptional reproducibility of normally off characteristics with centrally distributed threshold voltages (-0.37 ± 0.3 V) and realize large current and voltage handling capabilities and low static standby power consumption in a synergic manner with record-high on/off ratio exceeding 1010, high current density (∼200 µA·µm-1), ultralow off-state current (∼fA·µm-1), and high breakdown voltage (-676 V). Additionally, the thermal desorption of negatively charged acceptors has been proven to significantly reduce carrier scattering. This work offers superior performance p-channel FETs for implementing energy-efficient complementary circuits, laying the groundwork for accelerated development in wide bandgap semiconductor power electronics.

19.
Bioorg Chem ; 152: 107740, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39217780

RESUMO

Mimicking the transition state of tryptophan (Trp) and O2 in the enzymatic reaction is an effective approach to design indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors. In this study, we firstly assembled a small library of 2-substituted benzo-fused five membered heterocycles and found 2-sulfinyl-benzoxazoles with interesting IDO1 inhibitory activities. Next the inhibitory activity toward IDO1 was gradually improved. Several benzoxazoles showed potent IDO1 inhibitory activity with IC50 of 82-91 nM, and exhibited selectivity between IDO1 and tryptophan 2,3-dioxygenase (TDO2). Enzyme binding studies showed that benzoxazoles are reversible type II IDO1 inhibitors, and modeling studies suggested that the oxygen atom of the sulfoxide in benzoxazoles interacts with the iron atom of the heme group, which mimics the transition state of Fe-O-O-Trp complex. Especially, 10b can effectively inhibit the NO production in lipopolysaccharides (LPS) stimulated RAW264.7 cells, and it also shows good anti-inflammation effect on mice acute inflammation model of croton oil induced ear edema.


Assuntos
Benzoxazóis , Desenho de Fármacos , Inibidores Enzimáticos , Indolamina-Pirrol 2,3,-Dioxigenase , Lipopolissacarídeos , Animais , Camundongos , Indolamina-Pirrol 2,3,-Dioxigenase/antagonistas & inibidores , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Células RAW 264.7 , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/síntese química , Relação Estrutura-Atividade , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/antagonistas & inibidores , Benzoxazóis/farmacologia , Benzoxazóis/química , Benzoxazóis/síntese química , Estrutura Molecular , Edema/tratamento farmacológico , Edema/induzido quimicamente , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/síntese química , Relação Dose-Resposta a Droga , Inflamação/tratamento farmacológico , Humanos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/síntese química , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/metabolismo , Masculino
20.
J Environ Manage ; 370: 122559, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39340886

RESUMO

Aerobic composting is a useful method for managing and disposing of salvaged algal sludge. To optimize the composting process and improve compost quality, it is necessary to understand the functions and responses of microbial communities therein. This work studied the degradation process of organic matter and the assemblage of bacterial communities in algal sludge composting via 16S rRNA amplicon sequencing. The results showed that 77.08% of the microcystin was degraded during the thermophilic stage of composting, which was the main period for microcystin degradation. Bacterial community composition and diversity changed significantly during the composting, and gradually stabilized as the compost matured. Different composting stages may be dominated by different module groups separately, as shown in the co-occurrence networks of composting bacterial communities. In the networks, all bacteria associated with microcystin degradation were identified as connectors between different module groups. The algal sludge composting process was driven primarily by deterministic processes, and the main driving forces for bacterial community assembly were temperature, dissolved organic carbon, ammonium, and microcystin. At last, by applying the structural equation modeling method, the bacterial communities under influences of physiochemical properties were proved as the main mediators for the microcystin degradation. This study provides valuable insights into the optimization of bacterial communities in composting to improve the efficiency of microcystin degradation and the quality of the compost product.

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