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1.
Small Methods ; : e2400604, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39279575

RESUMO

2D metal-organic frameworks (2D MOFs) offer promising electrocatalytic potential for urea synthesis, yet the underlying reaction mechanisms and structure-activity relationships remain unclear. Using Cu-BDC as a model, density functional theory (DFT) calculations to elucidate these aspects are conducted. The results reveal a novel coupling mechanism involving *NO─CO and *NO─*ONCO, emphasizing the impact of linker modifications on Cu spin states and charge distribution. Notably, Cu-BDC-NH2 and Cu─BDC─OH emerge as promising catalysts. Additionally, structure-activity relationships through descriptors like d-band center, IE ratio, and L(Cu─O), providing insights for rational catalyst design is established. These findings pave the way for optimized catalysts and sustainable urea production, opening avenues for future research and technological advancements.

2.
J Neurooncol ; 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39225955

RESUMO

OBJECTIVE: This study aimed to develop a predictive model for cerebellar mutism syndrome (CMS) in pediatric patients with posterior fossa tumors, integrating lesion-symptom mapping (LSM) data with clinical factors, and to assess the model's performance. METHODS: A cohort of pediatric patients diagnosed with posterior fossa tumors and undergoing surgery at Beijing Children's Hospital from July 2013 to December 2023 was analyzed. Clinical variables gender, age at surgery, tumor characteristics, hydrocephalus, surgical route and pathology were collected. LSM was used to link tumor locations with CMS outcomes. Lasso regression and logistic regression were employed for feature selection and model construction, respectively. Model performance was assessed using area under the curve (AUC) and accuracy metrics. RESULTS: The study included 197 patients in total, with CMS rates consistent across training, validation, and prospective groups. Significant associations were found between CMS and gender, tumor type, hydrocephalus, paraventricular edema, surgical route, and pathology. A predictive model combining voxel location data from LSM with clinical factors achieved high predictive performance (C-index: training 0.956, validation 0.933, prospective 0.892). Gender, pathology, and voxel location were identified as key predictors for CMS. CONCLUSION: The study established an effective predictive model for CMS in pediatric posterior fossa tumor patients, leveraging LSM data and clinical factors. The model's accuracy and robustness suggest its potential utility in clinical practice for early CMS risk assessment and intervention planning.

3.
Neural Netw ; 180: 106691, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39255635

RESUMO

This research delves into the challenges of achieving secure consensus tracking within multi-agent systems characterized by directed hypergraph topologies, in the face of hybrid deception attacks. The hybrid discrete and continuous deception attacks are targeted at the controller communication channels and the hyperedges, respectively. To overcome these threats, an impulsive control mechanism based on hypergraph theory are introduced, and sufficient conditions are established, under which consensus can be maintained in a mean-square bounded sense, supported by rigorous mathematical proofs. Furthermore, the investigation quantifies the relationship between the mean-square bounded consensus of the multi-agent system and the intensity of the deception attacks, delineating a specific range for this error metric. The robustness and effectiveness of the proposed control method are verified through comprehensive simulation experiments, demonstrating its applicability in varied scenarios influenced by these sophisticated attacks. This study underscores the potential of hypergraph-based strategies in enhancing system resilience against complex hybrid attacks.

4.
Small ; : e2405158, 2024 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-39183524

RESUMO

The development of Cu-based atomic dispersed catalysts with tailored coordination environments represents a significant step forward in enhancing the electrocatalytic reduction of nitrate to ammonia. By precisely modulating the electronic structures of Cu active centers, the binding strength of the *NO3 intermediates is successfully tuned, thereby substantially improving the catalytic activity toward electrochemical nitrate reduction reaction (eNO3RR). This study reveals that the N4-coordinated Cu single-atom catalyst (Cu-SAC) exhibits superior performance due to its robust interaction with coordinating atoms. Notably, this optimized catalyst achieves a low limiting potential of -0.38 V, while the dual-atom system further reduces this value to -0.32 V, demonstrating exceptional activity. Detailed electronic structure analysis, including the examination of d-band centers, Bader charges, and projected density of states (PDOS), provides a comprehensive understanding of the origin of this high activity. Specifically, the high and concentrated density of states near the Fermi level plays a crucial role in facilitating the electrocatalytic nitrate reduction process. This work not only offers crucial insights into the underlying mechanisms of eNO3RR but also provides valuable guidelines for the rational design of highly efficient electrocatalysts for this important reaction.

5.
Nat Commun ; 15(1): 6740, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39112531

RESUMO

Glioblastoma (GBM) is the most common brain tumor and remains incurable. Primary GBM cultures are widely used tools for drug screening, but there is a lack of genomic and pharmacological characterization for these primary GBM cultures. Here, we collect 50 patient-derived glioma cell (PDGC) lines and characterize them by whole genome sequencing, RNA sequencing, and drug response screening. We identify three molecular subtypes among PDGCs: mesenchymal (MES), proneural (PN), and oxidative phosphorylation (OXPHOS). Drug response profiling reveals that PN subtype PDGCs are sensitive to tyrosine kinase inhibitors, whereas OXPHOS subtype PDGCs are sensitive to histone deacetylase inhibitors, oxidative phosphorylation inhibitors, and HMG-CoA reductase inhibitors. PN and OXPHOS subtype PDGCs stably form tumors in vivo upon intracranial transplantation into immunodeficient mice, whereas most MES subtype PDGCs fail to form tumors in vivo. In addition, PDGCs cultured by serum-free medium, especially long-passage PDGCs, carry MYC/MYCN amplification, which is rare in GBM patients. Our study provides a valuable resource for understanding primary glioma cell cultures and clinical translation and highlights the problems of serum-free PDGC culture systems that cannot be ignored.


Assuntos
Neoplasias Encefálicas , Glioma , Humanos , Animais , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Camundongos , Glioma/genética , Glioma/patologia , Glioma/tratamento farmacológico , Glioma/metabolismo , Fosforilação Oxidativa/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Glioblastoma/genética , Glioblastoma/patologia , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Feminino , Masculino , Sequenciamento Completo do Genoma , Ensaios Antitumorais Modelo de Xenoenxerto , Genômica/métodos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Multiômica
6.
Genome Biol ; 25(1): 232, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39198826

RESUMO

BACKGROUND: The relationship between human gut microbiota and high-altitude hypoxia acclimatization remains highly controversial. This stems primarily from uncertainties regarding both the potential temporal changes in the microbiota under such conditions and the existence of any dominant or core bacteria that may assist in host acclimatization. RESULTS: To address these issues, and to control for variables commonly present in previous studies which significantly impact the results obtained, namely genetic background, ethnicity, lifestyle, and diet, we conducted a 108-day longitudinal study on the same cohort comprising 45 healthy Han adults who traveled from lowland Chongqing, 243 masl, to high-altitude plateau Lhasa, Xizang, 3658 masl, and back. Using shotgun metagenomic profiling, we study temporal changes in gut microbiota composition at different timepoints. The results show a significant reduction in the species and functional diversity of the gut microbiota, along with a marked increase in functional redundancy. These changes are primarily driven by the overgrowth of Blautia A, a genus that is also abundant in six independent Han cohorts with long-term duration in lower hypoxia environment in Shigatse, Xizang, at 4700 masl. Further animal experiments indicate that Blautia A-fed mice exhibit enhanced intestinal health and a better acclimatization phenotype to sustained hypoxic stress. CONCLUSIONS: Our study underscores the importance of Blautia A species in the gut microbiota's rapid response to high-altitude hypoxia and its potential role in maintaining intestinal health and aiding host adaptation to extreme environments, likely via anti-inflammation and intestinal barrier protection.


Assuntos
Aclimatação , Altitude , Microbioma Gastrointestinal , Hipóxia , Humanos , Animais , Adulto , Masculino , Hipóxia/genética , Camundongos , Feminino , Estudos Longitudinais , Doença da Altitude/microbiologia , Doença da Altitude/genética , Pessoa de Meia-Idade
7.
Ecotoxicol Environ Saf ; 283: 116784, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39088896

RESUMO

2-ethylhexyl diphenyl phosphate (EHDPHP) is a widely used organophosphorus flame retardant and plasticizer, which is commonly found in the environment. EHDPHP not only potentially harms the environment but also causes different degrees of damage to the organism. In this study, the duodenum of chicks was selected as the potential toxic target organ to explore the mechanism of duodenal injury induced by EHDPHP exposure. Ninety one-day-old healthy male chicks were selected and randomly divided into C1(control group), C2(solvent control group), L(800 mg/kg), M(1600 mg/kg), H(3200 mg/kg) according to different doses of EHDPHP after one week of environmental adaptation. The chicks were given continuous gavage for 14 d, 28 d, and 42 d. It was found that constant exposure to EHDPHP caused an increase in duodenal MDA content, a decrease in P-gp, SOD, GSH-Px activities, and a decrease in duodenal mucosal immune factor (sIgA, GSH-Px). The expression of sIgM and mucosal link proteins (CLDN, OCLN, ZO-1, JAM) decreased, and the expression of the inflammatory protein (NF-κB, COX2) in duodenal tissues was up-regulated. The results showed that continuous exposure to EHDPHP could cause duodenal oxidative stress, inflammation, and mucosal barrier damage in chicks, which provided a basis for studying the mechanism of toxic damage caused by EHDPHP in poultry.


Assuntos
Galinhas , Duodeno , Retardadores de Chama , Estresse Oxidativo , Animais , Estresse Oxidativo/efeitos dos fármacos , Duodeno/efeitos dos fármacos , Duodeno/patologia , Duodeno/metabolismo , Masculino , Retardadores de Chama/toxicidade , Inflamação/induzido quimicamente , Inflamação/patologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Mucosa Intestinal/metabolismo , Compostos Organofosforados/toxicidade , Organofosfatos/toxicidade
8.
Langmuir ; 40(35): 18610-18618, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39172731

RESUMO

Low-cost sodium ion batteries are of great significance in large-scale energy storage applications. With its high energy density and simple synthesis process, layered transition-metal oxides have become one of the most likely sodium ion battery cathode materials to replace lithium ion batteries in the energy storage market. Here, we report a prilling and MoS2 coating strategy to prepare the spherical cathode material. The spherical micronano particles shorten the diffusion path of Na+, restrain the complexity phase transitions, and enhance the tap density of the materials. In addition, the MoS2 coating improves the electrical conductivity of the material and the structural stability of the cathode material in air. The initial specific discharge capacity is 148.4 mA h g-1 at 0.1 C, which can be maintained at 128.9 mA h g-1 after exposure to air for 10 days. This method dramatically improves the energy density and structural stability of the cathode material, which provides a new scheme for preparing high-performance sodium ion batteries.

9.
Biol Trace Elem Res ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958867

RESUMO

Cadmium(Cd) is a toxic heavy metal widely present in the environment, capable of accumulating in the liver and causing liver damage. In this study, the mechanism of cadmium-induced liver fibrosis in chickens was investigated from the perspective of hepatocyte epithelial-mesenchymal transition (EMT) based on the establishment of a model of chicken cadmium toxicity and a model of cadmium-stained cells in a chicken hepatocellular carcinoma cell line (LMH). The 7-day-old chickens were randomly divided into the regular group (C group) and cadmium poisoning group (Cd group), and the entire test cycle was 60 days. Three sampling time points of 20 days, 40 days, and 60 days were established. By testing the liver coefficient, histopathological and ultrastructural changes in chicken livers were observed. The enzyme activities of liver function and the expression changes of fibrosis markers (COL1A1, Fibronectin), epithelial-mesenchymal transition markers (E-cadherin, Vimentin, and α-SMA), and the critical factors of the TGF-ß/SMAD signaling pathway (TGF-ß1, SMAD 2, and SMAD 3) were detected in the liver expression changes. The results showed that at the same sampling time point, the chicken liver coefficient in group Cd was significantly higher than that in control group (P < 0.01); the activities of the liver function enzymes ALT and AST in chickens in the Cd group were significantly higher than those in the C group (P < 0.01); liver hepatocytes degenerated and necrotic, the number of erythrocytes in the blood vessels was increased, and inflammatory cells infiltrated in the sinusoidal gap; the perisinusoidal gap of the liver was enlarged, and there was an apparent aggregation of collagen fibers in the intervening period as seen by transmission electron microscopy. The results of Masson staining showed that the percentage of fiber area was significantly higher in the chickens' livers of the Cd group. The fiber area percentage was significantly higher. The results of real-time fluorescence quantitative PCR and Western Blot showed that the expression of E-cadherin in the livers of chickens in the Cd group was significantly lower than that in the C group (P < 0.01). The expression of α-SMA, Vimentin, COL1A1, Fibronectin, TGF-ß1, SMAD 2, and SMAD 3 was significantly higher than that in the C group (P < 0.01). The results of in vitro assays showed that in the LMH cell model established by adding trimethylamine N-oxide, an activator of the TGF-ß/SMAD signaling pathway, and oxidized picric acid, an inhibitor of the TGF-ß/SMAD signaling pathway, the expression of E-cadherin was significantly reduced in cadmium-stained LMH cells (P < 0.01). The expression of α-SMA, Vimentin, COL1A1, Fibronectin, TGF-ß, SMAD 2, and SMAD 3 was significantly elevated (P < 0.01). Cadmium and Trimethylamine N-oxide, an activator of the TGF-ß/SMAD signaling pathway, promoted the expression of these factors. In contrast, the inhibitor of the TGF-ß/SMAD signaling pathway, Oxymatrine, a TGF-ß/SMAD signaling pathway inhibitor, significantly slowed down these changes. These results suggest that cadmium induces hepatic epithelial-mesenchymal transition by activating the TGF-ß/SMAD signaling pathway in chicken hepatocytes, promoting hepatic fibrosis.

10.
Acta Pharmacol Sin ; 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39054339

RESUMO

Sjogren's syndrome (SS) is a chronic, progressive autoimmune disorder characterized by gland fibrosis. We previously found a close correlation between gland fibrosis and the expression of G protein-coupled receptor kinase 2 (GRK2). In this study we explored the pathological and therapeutic significance of GRK2 in SS. Submandibular gland (SMG) antigen-induced SS mouse model was established in WT and GRK2+/- mice. We showed that the expression levels of GRK2 were significantly up-regulated in glandular tissue and positively correlated with fibrotic morphology in SS patients and mice. Hemizygous knockout of GRK2 significantly inhibited the gland fibrosis. In mouse salivary gland epithelial cells (SGECs), we demonstrated that GRK2 interacted with Smad2/3 to positively regulate the activation of TGF-ß-Smad signaling with a TGF-ß-GRK2 positive feedback loop contributing to gland fibrosis. Hemizygous knockout of GRK2 attenuated TGF-ß-induced collagen I production in SGECs in vitro and hindered gland fibrosis in murine SS though preventing Smad2/3 nuclear translocation. Around 28 days post immunization with SMG antigen, WT SS mice were treated with a specific GRK2 inhibitor paroxetine (Par, 5 mg·kg-1·d-1, i.g. for 19 days). We found that Par administration significantly attenuated gland fibrosis and alleviated the progression of SS in mice. We conclude that genetic knockdown or pharmacological inhibition of GRK2 significantly attenuates gland fibrosis and alleviates the progression of SS. GRK2 binds to Smad2/3 and positively regulates the activation of TGF-ß-Smad signaling. A TGF-ß-GRK2 positive feedback loop contributes to gland fibrosis. Our research points out that GRK2 could be a promising therapeutic target for treating SS.

11.
Inorg Chem ; 63(29): 13181-13185, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-38985134

RESUMO

The development of a low-cost and efficient oxygen evolution reaction (OER) electrode is of critical importance for water electrolysis technologies. The general approach to achieving a high-efficiency OER electrode is to regulate catalytic material structures by synthetic control. Here we reported an orthogonal approach to obtaining the OER electrode without intentional design and synthesis, namely, recycling MnO2 cathodes from failed rechargeable aqueous batteries and investigating them as ready-made catalytic electrodes. The recycled MnO2 cathode showed very little Zn2+ storage capacity but surprisingly high OER activity with a low overpotential of 307 mV at 10 mA cm-2 and a small Tafel slope of 77.9 mV dec-1, comparable to the state-of-the-art RuO2 catalyst (310 mV, 86.9 mV dec-1). In situ electrochemical and theoretical studies jointly revealed that the accelerated OER kinetics of the recycled MnO2 electrode was attributed to the enlarged active surface area of MnO2 and optimized electronic structure of Mn sites. This work suggests failed battery cathodes as successful catalysis electrodes for sustainable energy development.

12.
Front Public Health ; 12: 1353384, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38939565

RESUMO

Background: Ozone pollution is associated with cardiovascular disease mortality, and there is a high correlation between different pollutants. This study aimed to assess the association between ozone and cardiovascular disease deaths and the resulting disease burden in Nanjing, China. Methods: A total of 151,609 deaths from cardiovascular disease were included in Nanjing, China from 2013 to 2021. Daily data on meteorological and air pollution were collected to apply a generalized additional model with multiple pollutants to perform exposure-response analyses, stratification analysis, and evaluation of excess deaths using various standards. Results: In the multi-pollutant model, an increase of 10 µg/m3 in O3 was significantly associated with a 0.81% (95%CI: 0.49, 1.12%) increase in cardiovascular disease deaths in lag05. The correlation weakened in both the single-pollutant model and two-pollutant models, but remained more pronounced in females, the older group, and during warm seasons. From 2013 to 2021, the number of excess deaths attributed to ozone exposure in cardiovascular disease continued to rise with an increase in ozone concentration in Nanjing. If the ozone concentration were to be reduced to the WHO standard and the minimum level, the number of deaths would decrease by 1,736 and 10,882, respectively. Conclusion: The risk of death and excess deaths from cardiovascular disease due to ozone exposure increases with higher ozone concentration. Reducing ozone concentration to meet WHO standards or lower can provide greater cardiovascular disease health benefits.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Doenças Cardiovasculares , Exposição Ambiental , Ozônio , Ozônio/análise , Ozônio/toxicidade , Ozônio/efeitos adversos , Humanos , Doenças Cardiovasculares/mortalidade , China/epidemiologia , Feminino , Masculino , Poluentes Atmosféricos/análise , Exposição Ambiental/efeitos adversos , Poluição do Ar/efeitos adversos , Pessoa de Meia-Idade , Idoso , Estações do Ano , Adulto , Rios
13.
Environ Technol ; : 1-12, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38940265

RESUMO

Antibiotics in water will cause serious harm to human health and ecosystem. Carbon-based materials and transition metals activated peroxodisulfate (PDS) to produce active species, which can degrade residual antibiotics in water. In this paper, Cu/CNF (carbon nanofibers) composites were first prepared by introducing Cu into CNF using electrostatic spinning technology, which was used to activate PDS to degrade tetracycline (TC). The degradation efficiency of Cu/CNF/PDS was 36.23% higher than that of CNF/PDS. The reason is that introducing Cu can increase the number of surface functional groups and specific surface area of CNF, and then improve the catalytic performance. The functional groups and Cu species are the active sites for catalytic PDS. Moreover, the main ways to degrade TC in the Cu/CNF/PDS system are singlet oxygen (1O2) and electron transfer. Based on the above analysis, we modified CNF with transition metal salts, prepared efficient environmental functional materials, and used them for PDS activation, providing a theoretical basis and technical support for the degradation of antibiotic pollutants and creating new ideas for other research.

14.
Chem Commun (Camb) ; 60(58): 7467-7470, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-38934088

RESUMO

A finely controlled concentration polarization environment was deliberately created to fabricate a three-dimensional ordered Zn metal anode with (002)-dominated planes, which enabled a high-rate aqueous Ni-Zn pouch cell with a high discharge capacity of 187.3 mA h g-1 at 50 C, and a capacity retention of 94.7% and an average Coulombic efficiency of 99.8% for 500 charge/discharge cycles.

15.
Langmuir ; 40(21): 11116-11124, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38738776

RESUMO

Layered transition metal oxides are commonly used as the cathode materials in sodium-ion batteries due to their low cost and easy manufacturing. However, the application is hindered by poor rate performance and complex phase transitions. To address these challenges, a new seven-component high-entropy layered oxide cathode material, O3-NaNi0.25Fe0.15Mn0.3Ti0.1Sn0.05Co0.05Li0.1O2 (HEO) has been developed. The entropy stabilization effect plays a crucial role in improving the performance of electrochemical systems and the stability of structures. The HEO exhibits a specific discharge capacity of 154.1 mA h g-1 at 0.1 C and 94.5 mA h g-1 at 7 C. In-situ and ex-situ XRD results demonstrate that the HEO effectively retards complex phase transitions. This work provides a high-entropy design for the storage materials with a high energy density. Meanwhile, it eliminates industry doubts about the performance of sodium ion layered oxide cathode materials.

16.
Comput Biol Med ; 176: 108530, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38749324

RESUMO

As an autoimmune-mediated inflammatory demyelinating disease of the central nervous system, multiple sclerosis (MS) is often confused with cerebral small vessel disease (cSVD), which is a regional pathological change in brain tissue with unknown pathogenesis. This is due to their similar clinical presentations and imaging manifestations. That misdiagnosis can significantly increase the occurrence of adverse events. Delayed or incorrect treatment is one of the most important causes of MS progression. Therefore, the development of a practical diagnostic imaging aid could significantly reduce the risk of misdiagnosis and improve patient prognosis. We propose an interpretable deep learning (DL) model that differentiates MS and cSVD using T2-weighted fluid-attenuated inversion recovery (FLAIR) images. Transfer learning (TL) was utilized to extract features from the ImageNet dataset. This pioneering model marks the first of its kind in neuroimaging, showing great potential in enhancing differential diagnostic capabilities within the field of neurological disorders. Our model extracts the texture features of the images and achieves more robust feature learning through two attention modules. The attention maps provided by the attention modules provide model interpretation to validate model learning and reveal more information to physicians. Finally, the proposed model is trained end-to-end using focal loss to reduce the influence of class imbalance. The model was validated using clinically diagnosed MS (n=112) and cSVD (n=321) patients from the Beijing Tiantan Hospital. The performance of the proposed model was better than that of two commonly used DL approaches, with a mean balanced accuracy of 86.06 % and a mean area under the receiver operating characteristic curve of 98.78 %. Moreover, the generated attention heat maps showed that the proposed model could focus on the lesion signatures in the image. The proposed model provides a practical diagnostic imaging aid for the use of routinely available imaging techniques such as magnetic resonance imaging to classify MS and cSVD by linking DL to human brain disease. We anticipate a substantial improvement in accurately distinguishing between various neurological conditions through this novel model.


Assuntos
Doenças de Pequenos Vasos Cerebrais , Aprendizado Profundo , Esclerose Múltipla , Humanos , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Esclerose Múltipla/diagnóstico por imagem , Masculino , Imageamento por Ressonância Magnética/métodos , Feminino , Redes Neurais de Computação , Interpretação de Imagem Assistida por Computador/métodos , Pessoa de Meia-Idade , Adulto , Neuroimagem/métodos
17.
Brain Res Bull ; 213: 110981, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38777132

RESUMO

INTRODUCTION: The medial prefrontal cortex (mPFC) forms output pathways through projection neurons, inversely receiving adjacent and long-range inputs from other brain regions. However, how afferent neurons of mPFC are affected by chronic stress needs to be clarified. In this study, the effects of chronic restraint stress (CRS) on the distribution density of mPFC dendrites/dendritic spines and the projections from the cortex and subcortical brain regions to the mPFC were investigated. METHODS: In the present study, C57BL/6 J transgenic (Thy1-YFP-H) mice were subjected to CRS to establish an animal model of depression. The infralimbic (IL) of mPFC was selected as the injection site of retrograde AAV using stereotactic technique. The effects of CRS on dendrites/dendritic spines and afferent neurons of the mPFC IL were investigaed by quantitatively assessing the distribution density of green fluorescent (YFP) positive dendrites/dendritic spines and red fluorescent (retrograde AAV recombinant protein) positive neurons, respectively. RESULTS: The results revealed that retrograde tracing virus labeled neurons were widely distributed in ipsilateral and contralateral cingulate cortex (Cg1), second cingulate cortex (Cg2), prelimbic cortex (PrL), infralimbic cortex, medial orbital cortex (MO), and dorsal peduncular cortex (DP). The effects of CRS on the distribution density of mPFC red fluorescence positive neurons exhibited regional differences, ranging from rostral to caudal or from top to bottom. Simultaneously, CRS resulted a decrease in the distribution density of basal, proximal and distal dendrites, as well as an increase in the loss of dendritic spines of the distal dendrites in the IL of mPFC. Furthermore, varying degrees of red retrograde tracing virus fluorescence signals were observed in other cortices, amygdala, hippocampus, septum/basal forebrain, hypothalamus, thalamus, mesencephalon, and brainstem in both ipsilateral and contralateral brain. CRS significantly reduced the distribution density of red fluorescence positive neurons in other cortices, hippocampus, septum/basal forebrain, hypothalamus, and thalamus. Conversely, CRS significantly increased the distribution density of red fluorescence positive neurons in amygdala. CONCLUSION: Our results suggest a possible mechanism that CRS leads to disturbances in synaptic plasticity by affecting multiple inputs to the mPFC, which is characterized by a decrease in the distribution density of dendrites/dendritic spines in the IL of mPFC and a reduction in input neurons of multiple cortices to the IL of mPFC as well as an increase in input neurons of amygdala to the IL of mPFC, ultimately causing depression-like behaviors.


Assuntos
Depressão , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Córtex Pré-Frontal , Restrição Física , Estresse Psicológico , Animais , Córtex Pré-Frontal/patologia , Córtex Pré-Frontal/metabolismo , Estresse Psicológico/patologia , Estresse Psicológico/metabolismo , Camundongos , Depressão/patologia , Masculino , Espinhas Dendríticas/patologia , Modelos Animais de Doenças , Vias Aferentes , Dendritos/patologia , Dendritos/metabolismo , Neurônios Aferentes/patologia , Neurônios Aferentes/metabolismo , Encéfalo/patologia , Encéfalo/metabolismo
18.
J Neurooncol ; 168(1): 139-149, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38662151

RESUMO

PURPOSE: Medulloblastoma (MB), a common and heterogeneous posterior fossa tumor in pediatric patients, presents diverse prognostic outcomes. To advance our understanding of MB's intricate biology, the development of novel patient tumor-derived culture MB models with necessary data is still an essential requirement. METHODS: We continuously passaged PUMC-MB1 in vitro in order to establish a continuous cell line. We examined the in vitro growth using Cell Counting Kit-8 (CCK-8) and in vivo growth with subcutaneous and intracranial xenograft models. The xenografts were investigated histopathologically with Hematoxylin and Eosin (HE) staining and immunohistochemistry (IHC). Concurrently, we explored its molecular features using Whole Genome Sequencing (WGS), targeted sequencing, and RNA sequecing. Guided by bioinformatics analysis, we validated PUMC-MB1's drug sensitivity in vitro and in vivo. RESULTS: PUMC-MB1, derived from a high-risk MB patient, displayed a population doubling time (PDT) of 48.18 h and achieved 100% tumor growth in SCID mice within 20 days. HE and Immunohistochemical examination of the original tumor and xenografts confirmed the classification of PUMC-MB1 as a classic MB. Genomic analysis via WGS revealed concurrent MYC and OTX2 amplifications. The RNA-seq data classified it within the Group 3 MB subgroup, while according to the WHO classification, it fell under the Non-WNT/Non-SHH MB. Comparative analysis with D283 and D341med identified 4065 differentially expressed genes, with notable enrichment in the PI3K-AKT pathway. Cisplatin, 4-hydroperoxy cyclophosphamide/cyclophosphamide, vincristine, and dactolisib (a selective PI3K/mTOR dual inhibitor) significantly inhibited PUMC-MB1 proliferation in vitro and in vivo. CONCLUSIONS: PUMC-MB1, a novel Group 3 (Non-WNT/Non-SHH) MB cell line, is comprehensively characterized for its growth, pathology, and molecular characteristics. Notably, dactolisib demonstrated potent anti-proliferative effects with minimal toxicity, promising a potential therapeutic avenue. PUMC-MB1 could serve as a valuable tool for unraveling MB mechanisms and innovative treatment strategies.


Assuntos
Neoplasias Cerebelares , Meduloblastoma , Inibidores de Fosfoinositídeo-3 Quinase , Serina-Treonina Quinases TOR , Animais , Humanos , Camundongos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias Cerebelares/tratamento farmacológico , Neoplasias Cerebelares/patologia , Neoplasias Cerebelares/genética , Neoplasias Cerebelares/metabolismo , Meduloblastoma/tratamento farmacológico , Meduloblastoma/patologia , Meduloblastoma/genética , Meduloblastoma/metabolismo , Camundongos SCID , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinases/genética , Inibidores de Fosfoinositídeo-3 Quinase/farmacologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Langmuir ; 40(18): 9556-9562, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38666374

RESUMO

Direct regeneration has gained much attention in LiFePO4 battery recycling due to its simplicity, ecofriendliness, and cost savings. However, the excess carbon residues from binder decomposition, conductive carbon, and coated carbon in spent LiFePO4 impair electrochemical performance of direct regenerated LiFePO4. Herein, we report a preoxidation and prilling collaborative doping strategy to restore spent LiFePO4 by direct regeneration. The excess carbon is effectively removed by preoxidation. At the same time, prilling not only reduces the size of the primary particles and shortens the diffusion distance of Li+ but also improves the tap density of the regenerated materials. Besides, the Li+ transmission of the regenerated LiFePO4 is further improved by Ti4+ doping. Compared with commercial LiFePO4, it has excellent low-temperature performance. The collaborative strategy provides a new insight into regenerating high-performance spent LiFePO4.

20.
Brain Behav ; 14(3): e3430, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38433103

RESUMO

BACKGROUND: Craniopharyngiomas are low-grade malignancies (WHO I) in the sellar region. Most cases of childhood-onset craniopharyngioma are adamantinomatous craniopharyngioma, and neurosurgery is the treatment of choice. Affected patients have postoperative complications, including water and electrolyte disturbances, because these malignancies develop near the hypothalamus and pituitary gland. Determining postoperative serum sodium fluctuation patterns in these patients can reduce postoperative mortality and improve prognosis. OBJECTIVE: To measure changes in serum sodium levels in pediatric patients who underwent craniopharyngioma surgery and identify influencing factors. METHODS: This retrospective study measured the serum sodium levels of 202 patients aged 0-18 years who underwent craniopharyngioma resection in Beijing Tiantan Hospital and Beijing Children's Hospital and identified predictors of severe hyponatremia and hypernatremia. RESULTS: The mean age of the cohort was 8.35 ± 4.35 years. The prevalence of hypernatremia, hyponatremia, and their severe forms (serum Na+  > 150 mmol/L and serum Na+  < 130 mmol/L) within 14 days after surgery was 66.3%, 72.8%, 37.1%, and 40.6%, respectively. The mean postoperative serum sodium level showed a triphasic pattern, characterized by two peaks separated by a nadir. Sodium levels peaked on days 2 (143.6 ± 7.6 mmol/L) and 14 (143.2 ± 6.7 mmol/L) and reached their lowest on day 6 (135.5 ± 7.5 mmol/L). A total of 31 (15.3%) patients met the diagnostic threshold for hyponatremia and hypernatremia of the triphase response, whereas 116 (57.4%) patients presented this pattern, regardless of met the diagnostic criteria or not. The prevalence of severe hyponatremia varied depending on preoperative endocrine hormone deficiency, tumor status (primary or recurrent), and surgical approach. CONCLUSIONS: Serum sodium levels after craniopharyngioma resection in children showed a triphasic pattern in most cases. The risk of postoperative hyponatremia varied depending on preoperative endocrine hormone deficiency, tumor status (primary or recurrent), and surgical approach.


Assuntos
Craniofaringioma , Hipernatremia , Hiponatremia , Neoplasias Hipofisárias , Humanos , Criança , Pré-Escolar , Craniofaringioma/cirurgia , Hipernatremia/epidemiologia , Hipernatremia/etiologia , Hiponatremia/epidemiologia , Hiponatremia/etiologia , Estudos Retrospectivos , Neoplasias Hipofisárias/cirurgia , Hormônios , Sódio
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