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1.
J Diabetes Investig ; 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39254788

RESUMO

AIMS/INTRODUCTION: To assess whether the sodium-glucose cotransporter 2 inhibitor, henagliflozin, improves cognitive impairment in patients with type 2 diabetes. MATERIALS AND METHODS: We carried out a prospective study on 290 patients with type 2 diabetes and cognitive impairment. Montreal Cognitive Assessment scores and plasma phosphorylated tau181 levels were used to assess cognition. The association between henagliflozin use and changes in cognition was examined using multivariable logistic regression analysis. RESULTS: Montreal Cognitive Assessment scores at enrollment and after 6 months were 21 (interquartile range [IQR]19-23) versus 22 (IQR 20-25; P < 0.0001) in all patients, 21 (IQR 19-23) versus 24 (IQR 22-26; P < 0.0001) in the henagliflozin group and 21 (IQR 19-22) versus 21 (IQR 19-23; P > 0.05) in the non-sodium-glucose cotransporter 2 inhibitor group. Logistic regression analysis showed that henagliflozin treatment was associated with Montreal Cognitive Assessment score improvement independent of potential confounders (odds ratio [OR] 3.670, 95% confidence interval [CI] 2.224-6.056, P < 0.0001). Additionally, plasma phosphorylated tau181 levels significantly decreased at 6-month follow up in all patients (OR 11.5, 95% CI 9.9-13.7 vs OR 10.1, 95% CI 7.8-12.9, P < 0.0001) and in the henagliflozin group (OR 11.5, 95% CI 10.3-13.0 vs OR 9.2, 95% CI 7.1-10.7, P < 0.0001), but not in the non-sodium-glucose cotransporter 2 inhibitor group. Henagliflozin treatment was independently associated with decreased phosphorylated tau181 levels (OR 3.670, 95% CI 1.598-4.213, P < 0.0001). CONCLUSIONS: Henagliflozin treatment was independently associated with improvements in Montreal Cognitive Assessment scores and plasma phosphorylated tau181 levels, indicating significant beneficial effects on cognitive impairment in patients with type 2 diabetes.

2.
Commun Biol ; 7(1): 1104, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39251833

RESUMO

Many biological problems are understudied due to experimental limitations and human biases. Although deep learning is promising in accelerating scientific discovery, its power compromises when applied to problems with scarcely labeled data and data distribution shifts. We develop a deep learning framework-Meta Model Agnostic Pseudo Label Learning (MMAPLE)-to address these challenges by effectively exploring out-of-distribution (OOD) unlabeled data when conventional transfer learning fails. The uniqueness of MMAPLE is to integrate the concept of meta-learning, transfer learning and semi-supervised learning into a unified framework. The power of MMAPLE is demonstrated in three applications in an OOD setting where chemicals or proteins in unseen data are dramatically different from those in training data: predicting drug-target interactions, hidden human metabolite-enzyme interactions, and understudied interspecies microbiome metabolite-human receptor interactions. MMAPLE achieves 11% to 242% improvement in the prediction-recall on multiple OOD benchmarks over various base models. Using MMAPLE, we reveal novel interspecies metabolite-protein interactions that are validated by activity assays and fill in missing links in microbiome-human interactions. MMAPLE is a general framework to explore previously unrecognized biological domains beyond the reach of present experimental and computational techniques.


Assuntos
Aprendizado de Máquina Supervisionado , Humanos , Aprendizado Profundo , Microbiota , Biologia Computacional/métodos
3.
Curr Issues Mol Biol ; 46(9): 10618-10632, 2024 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-39329981

RESUMO

Ophiocordyceps sinensis (Berk.) is a complex is formed by Hepialidae larvae and Hirsutella sinensis. Infestation by H. sinensis, interaction with host larvae, and fruiting body development are three crucial processes affecting the formation of O. sinensis. However, research on the molecular mechanism of O. sinensis formation has been hindered by the lack of effective genetic transformation protocols. Therefore, Agrobacterium tumefaciens-mediated transformation (ATMT) was adopted to genetically transform two H. sinensis strains and optimize the transformation conditions. The results revealed that the most suitable Agrobacterium strain for H. sinensis transformation was AGL1, and that the surfactant Triton X-100 could also induce ATMT, although less effectively than acetosyringone (AS). In addition, the endogenous promoters of H. sinensis genes had a stronger ability to drive the expression of the target gene than did the exogenous promoter. The optimal transformation conditions were as follows: AS and hygromycin B concentrations of 100 µM and 50 µg/mL, respectively; A. tumefaciens OD600 of 0.4; cocultivation at 18 °C for 24 h; and H. sinensis used within three passages. The results lay a foundation for the functional study of key regulatory genes involved in the formation of O. sinensis.

4.
Front Pediatr ; 12: 1416778, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39323510

RESUMO

Objective: To evaluate the effect of nutritional risk management program on the growth and development of infants and toddlers with congenital heart disease (CHD) after discharge. Methods: Infants and toddlers with CHD discharged from a children's specialized hospital in southeast China were selected as the research subjects. The subjects were divided into the intervention group and the control group. The intervention group underwent a nutritional risk management program combined with traditional follow-up after discharge, whereas the control group received traditional follow-up after discharge. The primary outcome measure were the height-for-age Z-score (HAZ), weight-for-age Z-score (WAZ), and weight-for-height Z-score (WHZ) at different time point and the percentage of growth and development curves were also recorded and analyzed. Results: There were no statistically significant differences in general characteristics between the two groups. However, in the intervention group, the percentages of HAZ < -2, WAZ < -2, and WHZ < -2 were lower than those in the control group at 3rd and 6th months after discharge (P < 0.05). The percentage of growth and development curves (3%-97%) was higher than that in the control group (P < 0.05). The readmission rate within 6 months after discharge in the intervention group was lower than that in the control group (P < 0.05). Conclusion: Implementing nutritional risk management program for infants and toddlers with CHD after discharge can help improve postoperative malnutrition, promote growth and development and achieve catch-up growth as soon as possible.

5.
Water Res ; 267: 122472, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39305525

RESUMO

This study examined the influence of water periods on river nitrogen cycling by analysing nitrogen functional genes and bacterial communities in the Qingshui River, an upstream tributary of the Yellow River in China. Nitrate nitrogen predominated as inorganic nitrogen during the low-flow seasons, whereas salinity was highest during the high-flow seasons. Overall, the functional gene abundance increased with decreasing water volume, and nitrogen concentrations were determined by various specific gene groups. The relative abundance of bacteria carrying these genes varied significantly across water periods. The abundance of Pseudomona, Hydrogenophaga (carrying narGHI and nirB genes), and Flavobacterium (carrying nirK, norBC, and nosZ genes) significantly increased during the low-flow seasons. Nitrogen transformation bacteria exhibited both symbiotic and mutualistic relationships. Microbial network nodes and sizes decreased with decreasing water volume, whereas modularity increased. Additionally, the water period affected the functional microbial community structure by influencing specific environmental factors. Among them, SO42- primarily determined the denitrification, dissimilatory nitrate reduction to ammonium, and assimilatory nitrate reduction to ammonium communities, whereas NO2--N and Mg2+ were the main driving factors for the nitrogen-fixing and nitrifying communities, respectively. These findings have substantial implications for better understanding the reduction in river nitrogen loads in arid and semi-arid regions during different water periods.

6.
Eco Environ Health ; 3(3): 271-280, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39252856

RESUMO

Freshwater salinization is receiving increasing global attention due to its profound influence on nitrogen cycling in aquatic ecosystems and the accessibility of water resources. However, a comprehensive understanding of the changes in river salinization and the impacts of salinity on nitrogen cycling in arid and semi-arid regions of China is currently lacking. A meta-analysis was first conducted based on previous investigations and found an intensification in river salinization that altered hydrochemical characteristics. To further analyze the impact of salinity on nitrogen metabolism processes, we evaluated rivers with long-term salinity gradients based on in situ observations. The genes and enzymes that were inhibited generally by salinity, especially those involved in nitrogen fixation and nitrification, showed low abundances in three salinity levels. The abundance of genes and enzymes with denitrification and dissimilatory nitrate reduction to ammonium functions still maintained a high proportion, especially for denitrification genes/enzymes that were enriched under medium salinity. Denitrifying bacteria exhibited various relationships with salinity, while dissimilatory nitrate reduction to ammonium bacterium (such as Hydrogenophaga and Curvibacter carrying nirB) were more inhibited by salinity, indicating that diverse denitrifying bacteria could be used to regulate nitrogen concentration. Most genera exhibited symbiotic and mutual relationships, and the highest proportion of significant positive correlations of abundant genera was found under medium salinity. This study emphasizes the role of river salinity on environment characteristics and nitrogen transformation rules, and our results are useful for improving the availability of river water resources in arid and semi-arid regions.

7.
Integr Zool ; 2024 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-39245877

RESUMO

We found that embryonic behavioral thermoregulation could not enhance the thermoregulatory capacity of turtle hatchlings. Our study is not only the first to provide experimental evidence regarding the impact of embryonic behavioral thermoregulation on offspring thermoregulation but also falsifies the play behavior hypothesis that suggests thermotaxis by embryos allows them to practice thermoregulatory tactics at later life stages.

8.
Chem Commun (Camb) ; 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39295587

RESUMO

A straightforward method for the dehydrogenative alkylation of quinoxalin-2(1H)-ones with alkylbenzenes has been developed, facilitated by a photoexcited nitroarene. The reaction's success hinges on the dual role of the photoexcited nitroarene molecule, acting as both a hydrogen atom transfer (HAT) reagent and an oxidant. This technique is both atom-economical and cost-effective, due to the readily available nitroarene, which serves as the sole intermediary in the reaction process.

9.
Nano Lett ; 24(37): 11690-11696, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39225657

RESUMO

Precise monitoring of biomolecular radiation damage is crucial for understanding X-ray-induced cell injury and improving the accuracy of clinical radiotherapy. We present the design and performance of lanthanide-DNA-origami nanodosimeters for directly visualizing radiation damage at the single-particle level. Lanthanide ions (Tb3+ or Eu3+) coordinated with DNA origami nanosensors enhance the sensitivity of X-ray irradiation. Atomic force microscopy (AFM) revealed morphological changes in Eu3+-sensitized DNA origami upon X-ray irradiation, indicating damage caused by ionization-generated electrons and free radicals. We further demonstrated the practical applicability of Eu3+-DNA-origami integrated chips in precisely monitoring radiation-mediated cancer radiotherapy. Quantitative results showed consistent trends with flow cytometry and histological examination under comparable X-ray irradiation doses, providing an affordable and user-friendly visualization tool for preclinical applications. These findings provide new insights into the impact of heavy metals on radiation-induced biomolecular damage and pave the way for future research in developing nanoscale radiation sensors for precise clinical radiography.


Assuntos
DNA , Elementos da Série dos Lantanídeos , Microscopia de Força Atômica , DNA/química , DNA/análise , Humanos , Elementos da Série dos Lantanídeos/química , Raios X , Dano ao DNA , Európio/química
10.
J Ginseng Res ; 48(5): 454-463, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39263308

RESUMO

Background: Panax quinquefolius L, widely recognized for its valuable contributions to medicine, has aroused considerable attention globally. Different from the extensive research has been dedicated to the root of P. quinquefolius, its berry has received relatively scant focus. Given its promising medicinal properties, this study was focused on the structural characterizations and anti-inflammatory potential of acidic polysaccharides from the P. quinquefolius berry. Materials and methods: P. quinquefolius berry was extracted with hot water, precipitated by alcohol, separated by DEAE-52-cellulose column to give a series of fractions. One of these fractions was further purified via Sephadex G-200 column to give three fractions. Then, the main fraction named as AGBP-A3 was characterized by methylation analysis, NMR spectroscopy, etc. Its anti-inflammatory activity was assessed by RAW 264.7 cell model, zebrafish model and molecular docking. Results: The main chain comprised of α-L-Rhap, α-D-GalAp and ß-D-Galp, while the branch consisted mainly of α-L-Araf, ß-D-Glcp, α-D-GalAp, ß-D-Galp. The RAW264.7 cell assay results showed that the inhibition rates against IL-6 and IL-1ß secretion at the concentration of 625 ng/mL were 24.83 %, 11.84 %, while the inhibition rate against IL-10 secretion was 70.17 % at the concentration of 312 ng/mL. In the zebrafish assay, the migrating neutrophils were significantly reduced in number, and their migration to inflammatory tissues was inhibited. Molecular docking predictions correlated well with the results of the anti-inflammatory assay. Conclusion: The present study demonstrated the structure of acidic polysaccharides of P. quinquefolius berry and their effect on inflammation, providing a reference for screening anti-inflammatory drugs.

11.
Langmuir ; 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39276096

RESUMO

Interfacial interactions between deformable bubbles and oil drops have attracted much attention in foam flooding. However, interactions involving nitrogen bubbles have not been reported. In this work, the interaction forces between nitrogen and dodecane/toluene in aqueous solutions were quantified using the atomic force microscopy bubble probe technique. The effects of the solution pH, ionic type, and solution concentration on the interactions were analyzed. The van der Waals (vdW), electric double layer (EDL), and hydrophobic (HB) interactions were involved in the low-concentration solutions. The EDL repulsion in NaCl increased with solution pH, while in CaCl2 and MgCl2, the EDL repulsion in general decreased and then increased with pH, attributed to the adsorption of OH- and divalent cations and their hydration products. The adsorption of divalent cations at the toluene/water interface was pronounced by cation-π interactions. At pH 10, precipitated divalent cation hydroxides at the bubble/water and oil/water interfaces adsorbed more cations, causing the increase of the surface potential. At high salinity, the EDL interaction was suppressed and the vdW repulsion became predominant. The vdW force of nitrogen with toluene was stronger than that with dodecane. Under all of the solution conditions, the attractive interaction could not overcome the total repulsive interaction at the minimum separation, and thus no bubble attachment was observed, which implied that a stable bubble/liquid/oil film was essential for maintaining foam stability. This work provides useful insights into the interfacial interaction mechanisms in nitrogen foam flooding. The findings can be readily extended to other engineering systems such as oil flotation and bubble-oil-water emulsions.

12.
Brief Bioinform ; 25(5)2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39288232

RESUMO

DNA molecules as storage media are characterized by high encoding density and low energy consumption, making DNA storage a highly promising storage method. However, DNA storage has shortcomings, especially when storing multimedia data, wherein image reconstruction fails when address errors occur, resulting in complete data loss. Therefore, we propose a parity encoding and local mean iteration (PELMI) scheme to achieve robust DNA storage of images. The proposed parity encoding scheme satisfies the common biochemical constraints of DNA sequences and the undesired motif content. It addresses varying pixel weights at different positions for binary data, thus optimizing the utilization of Reed-Solomon error correction. Then, through lost and erroneous sequences, data supplementation and local mean iteration are employed to enhance the robustness. The encoding results show that the undesired motif content is reduced by 23%-50% compared with the representative schemes, which improves the sequence stability. PELMI achieves image reconstruction under general errors (insertion, deletion, substitution) and enhances the DNA sequences quality. Especially under 1% error, compared with other advanced encoding schemes, the peak signal-to-noise ratio and the multiscale structure similarity address metric were increased by 10%-13% and 46.8%-122%, respectively, and the mean squared error decreased by 113%-127%. This demonstrates that the reconstructed images had better clarity, fidelity, and similarity in structure, texture, and detail. In summary, PELMI ensures robustness and stability of image storage in DNA and achieves relatively high-quality image reconstruction under general errors.


Assuntos
Algoritmos , DNA , DNA/genética , Processamento de Imagem Assistida por Computador/métodos , Armazenamento e Recuperação da Informação/métodos
13.
Int J Biol Macromol ; 278(Pt 3): 134609, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39134197

RESUMO

Bacterial infections, excessive reactive oxygen species (ROS) accumulation and a persistent inflammatory response severely impede the wound healing process. In this study, we developed a novel multifunctional hydrogel dressing (LCPN) based on lipoic acid modified chitosan (LAMC), polypyrrole nanoparticles (PPy NPs) and nicotinamide mononucleotide (NMN) for accelerated healing of infected wounds. The synthesized LCPN hydrogel has several properties. Modification of lipoic acid significantly enhances the water solubility of chitosan making it easier to dissolve and absorb wound secretions. Interestingly, owing to the breaking and restructuring of disulfide bonds, LCPN hydrogel can be quickly bonded under UV light without relying on photoinitiators. In addition, the incorporation of PPy NPs not only enhances the electrical conductivity of LCPN hydrogel, but also confers photothermal antimicrobial capability to LCPN hydrogel. More importantly, the sustained release of NMN in LCPN hydrogel can significantly enhance cell proliferation, migration and antioxidant capacity, which is conducive to accelerated wound healing. In vitro and in vivo experiments have shown that LCPN hydrogel has excellent biocompatibility and the ability to promote wound healing. Therefore, the prepared multifunctional hydrogel is expected to be used as a novel dressing to accelerate wound healing.


Assuntos
Bandagens , Quitosana , Hidrogéis , Cicatrização , Quitosana/química , Quitosana/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Hidrogéis/química , Hidrogéis/farmacologia , Camundongos , Nanopartículas/química , Infecção dos Ferimentos/tratamento farmacológico , Antioxidantes/farmacologia , Antioxidantes/química , Luz , Proliferação de Células/efeitos dos fármacos , Polímeros/química , Humanos , Antibacterianos/farmacologia , Antibacterianos/química
14.
Infect Drug Resist ; 17: 3491-3499, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39157746

RESUMO

Background: Linezolid (LZD) is a cornerstone medication in the treatment of drug-resistant tuberculosis (DR-TB). However, it frequently triggers adverse effects such as bone marrow suppression, optic neuropathy, and peripheral neuropathy, all of which can impact treatment outcomes and prognosis. Contezolid (CZD), a novel oxazolidinone antibiotic, exhibits comparable antimicrobial efficacy against Mycobacterium tuberculosis as LZD, but with potentially enhanced safety profiles. Case Presentation: This report presents five cases (Cases 1-5) of LZD intolerance, wherein CZD served as an effective alternative treatment. In Cases 1-3, LZD administration resulted in bone marrow suppression, primarily manifested as anemia. Transitioning to CZD therapy led to a rise and stabilization of hemoglobin (HGB) levels in Cases 1-2, and a return to baseline values in Case 3. In Case 4, CZD treatment alleviated symptoms of LZD-induced peripheral neuritis, although complete resolution was not achieved, hinting at potential irreversibility of this type of peripheral neuropathy. In Case 5, direct CZD anti-TB therapy was initiated for recurrent leukopenia and neutropenia, resulting in no further severe myelosuppression and successful recovery. Conclusion: These case studies suggest that CZD could represent an effective and safe option for anti-TB therapy, especially for patients intolerant to LZD.

15.
J Anesth ; 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39164406

RESUMO

PURPOSE: Ultrasound view of the interlaminar structure is likely to be associated with difficult spinal anesthesia (DSA), and a poor ultrasound view which cannot show the anterior and posterior complex predicts a difficult spinal technique. As our target site is the posterior complex, this study aimed to assess whether the ratio of posterior complex length to depth measured by ultrasound can predict DSA in cesarean delivery. METHODS: Four anesthesiologists with 1-2 years of experience located and marked the puncture interspace using a traditional surface landmark. Subsequently, the ultrasound examiner located and measured the marked interspace via an oblique parasagittal ultrasound scan. The anesthesiologists, who were blinded to the ultrasound results, performed spinal anesthesia using a 25-gauge Whitacre spinal needle. The total number of attempts, including skin punctures and needle passes, was recorded and the DSA was defined as 10 unsuccessful attempts. A multivariable logistic regression analysis was used to determine the independent predictors, and receiver operating characteristic curves were constructed to evaluate the performance of the ratio of posterior complex length to depth for predicting DSA. RESULTS: A total of 397 cesarean delivery parturients with successfully measured posterior complex were included in the analysis. DSA occurred in 64 parturients (16.1%). Reduced length [odds ratio (OR) = 0.010, 95% confidence interval (CI), 0.002-0.062, P < 0.001] and increased depth [OR = 6.127, 95% CI, 2.671-14.056, P < 0.001] of the posterior complex were independently predictive of DSA compared with body mass index, abdominal circumference, and palpable surface landmarks. The ratio of posterior complex length to depth for predicting DSA had an area under the curve of 0.86 (95% CI, 0.82-0.90). The optimal cutoff was 0.23, with a sensitivity of 86% (95% CI, 74-93%) and specificity of 72% (95% CI, 67-77%). CONCLUSION: The ratio of posterior complex length to depth measured by ultrasound demonstrated a considerable accuracy in predicting DSA for inexperienced anesthesiologists. A higher ratio at ultrasound is an indication to evaluate the optimal puncture body position and interspace in the clinic practice. CLINICAL TRIAL REGISTRATION: ChiCTR2200065171 https://www.chictr.org.cn/showproj.html?proj=180855.

16.
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
17.
J Neuroinflammation ; 21(1): 192, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39095838

RESUMO

BACKGROUND: Type 2 diabetes mellitus (T2D) is associated with an increased risk of cognitive dysfunction. Angiopoietin-like protein 8 (ANGPTL8) is an important regulator in T2D, but the role of ANGPTL8 in diabetes-associated cognitive dysfunction remains unknown. Here, we explored the role of ANGPTL8 in diabetes-associated cognitive dysfunction through its interaction with paired immunoglobulin-like receptor B (PirB) in the central nervous system. METHODS: The levels of ANGPTL8 in type 2 diabetic patients with cognitive dysfunction and control individuals were measured. Mouse models of diabetes-associated cognitive dysfunction were constructed to investigate the role of ANGPTL8 in cognitive function. The cognitive function of the mice was assessed by the Barnes Maze test and the novel object recognition test, and levels of ANGPTL8, synaptic and axonal markers, and pro-inflammatory cytokines were measured. Primary neurons and microglia were treated with recombinant ANGPTL8 protein (rA8), and subsequent changes were examined. In addition, the changes induced by ANGPTL8 were validated after blocking PirB and its downstream pathways. Finally, mice with central nervous system-specific knockout of Angptl8 and PirB-/- mice were generated, and relevant in vivo experiments were performed. RESULTS: Here, we demonstrated that in the diabetic brain, ANGPTL8 was secreted by neurons into the hippocampus, resulting in neuroinflammation and impairment of synaptic plasticity. Moreover, neuron-specific Angptl8 knockout prevented diabetes-associated cognitive dysfunction and neuroinflammation. Mechanistically, ANGPTL8 acted in parallel to neurons and microglia via its receptor PirB, manifesting as downregulation of synaptic and axonal markers in neurons and upregulation of proinflammatory cytokine expression in microglia. In vivo, PirB-/- mice exhibited resistance to ANGPTL8-induced neuroinflammation and synaptic damage. CONCLUSION: Taken together, our findings reveal the role of ANGPTL8 in the pathogenesis of diabetes-associated cognitive dysfunction and identify the ANGPTL8-PirB signaling pathway as a potential target for the management of this condition.


Assuntos
Proteína 8 Semelhante a Angiopoietina , Proteínas Semelhantes a Angiopoietina , Disfunção Cognitiva , Diabetes Mellitus Tipo 2 , Camundongos Knockout , Receptores Imunológicos , Transdução de Sinais , Animais , Camundongos , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/prevenção & controle , Disfunção Cognitiva/etiologia , Transdução de Sinais/fisiologia , Transdução de Sinais/efeitos dos fármacos , Proteínas Semelhantes a Angiopoietina/metabolismo , Proteínas Semelhantes a Angiopoietina/genética , Humanos , Masculino , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Receptores Imunológicos/metabolismo , Receptores Imunológicos/genética , Camundongos Endogâmicos C57BL , Sinapses/metabolismo , Sinapses/patologia , Sinapses/efeitos dos fármacos , Hormônios Peptídicos/metabolismo , Pessoa de Meia-Idade , Feminino
18.
Angew Chem Int Ed Engl ; : e202411066, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39092491

RESUMO

Energy storage in supercapacitors and hybrid zinc ion capacitors (ZIC) using porous carbon materials offers a promsing alternative method for clean energy solutions. The unique combination of hierarchical porous structure and nitrogen doping in these materials has demonstrated significant capacity for energy storage. Nevertheless, the full potential of these materials, particularly the relationship between pore structure configuration and performance, remains underexplored. Herein, a confined pyrolysis strategy based on the polymerization characteristics of polydopamine (PDA) was developed to construction of hollow carbon spheres with microporous/mesoporous dual shell structure. The depth of micropores and cavity can be controlled by adjusting the duration of heat treatment and hydrothermal treatment, in accordance with the decomposition and polymerization characteristics of PDA. Due to the elasticity of this structure, the relationship between the micro/mesoporous depth of the prepared carbon spheres and the energy storage performance in supercapacitors and ZIC is established. Through optimizing the ion transport capacity of carbon spheres and considering the influence of its internal cavity structure on energy storage, the resulting carbon spheres exhibit high specific capacitance of 389 F g-1 in supercapacitor and specific capacitance of 260 F g-1 and excellent stability with 99.3% retention after 30000 chare/discharge cycles in ZIC.

19.
Sci Total Environ ; 951: 175824, 2024 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-39197756

RESUMO

Oyster farming activities play a pivotal role in the biogeochemical cycles of coastal marine ecosystems, particularly in terms of sedimentary carbon cycling. To gain deep insights into the influence of expanding oyster culture on the sedimentary carbon cycle, surface sediments were collected from the Maowei Sea, which is the largest oyster farming bay in south China, based on six filed surveys between July 2010 and December 2022. The sediment samples were analyzed for total organic carbon (TOC), total nitrogen (TN), stable carbon and nitrogen isotopes (δ13C and δ15N) to evaluate the inter-annual variations in the source contribution to sedimentary organic matter (SOM). The results revealed that the average contents of sedimentary TOC and TN were 0.67 ± 0.41 % and 0.06 ± 0.03 %, respectively. Fluctuations in the C/N molar ratios ranged from 5.8 to 23.6, with an average of 12.6 ± 2.9, indicating a significant terrestrial input contribution to SOM in the study area. Furthermore, the integration of stable isotope analysis and Bayesian mixing model demonstrated a gradual increase in the mean proportion of shellfish biodeposition to SOM, from 12.0 ± 5.6 % in July 2010 to 21.1 ± 7.3 % in December 2022, consistent with the progressive expansion of oyster aquaculture along this coastal area, thereby emphasizing the substantial influence of oyster farming on SOM composition. With the anticipated expansion of oyster farming scale and production in the future, shellfish biodeposition is expected to assume a more important role in shaping SOM dynamics and sedimentary organic carbon cycling in coastal waters. Overall, this study provided an important perspective for better assessing the impact of expanding mariculture scale on coastal biogeochemical cycles, thereby making valuable contributions to future policy formulation concerning mariculture and ecological conservation.


Assuntos
Aquicultura , Baías , Monitoramento Ambiental , Sedimentos Geológicos , Ostreidae , Sedimentos Geológicos/química , Animais , China , Carbono/análise , Nitrogênio/análise , Isótopos de Carbono/análise , Ciclo do Carbono
20.
Biomedicines ; 12(8)2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39200168

RESUMO

BACKGROUND: Cognitive impairment is a prevalent complication of type 2 diabetes, influenced significantly by various dietary patterns. High-carbohydrate diets (HCDs) are commonly consumed nowadays; however, the specific impact of HCDs on cognitive function in diabetes remains unclear. METHODS: The objective of this study was to investigate whether an HCD has effects on cognition in diabetes. Eight-week-old diabetic (db/db) mice and wild-type (WT) mice underwent a twelve-week dietary intervention, including a normal diet (ND), an HCD, or a high-fat diet (HFD). Following this, behavioral tests were conducted, and related hippocampal pathology was evaluated. RESULTS: Our results demonstrated that an HCD exacerbated cognitive decline in db/db mice compared to an ND. Additionally, an HCD increased amyloid-ß burden and expression of ß-site APP cleaving enzyme-1. An HCD was also found to promote the phosphorylation of tau protein via the PI3K/Akt/GSK-3ß pathway. Furthermore, an HCD markedly induced neuroinflammation and increased the quantity of microglia and astrocytes. However, these damages induced by an HCD were less severe than those caused by an HFD. CONCLUSIONS: Collectively, our findings indicate that a high intake of carbohydrates can have an adverse impact on cognitive function in diabetes.

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