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1.
Int J Surg Case Rep ; 119: 109773, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38772244

RESUMO

INTRODUCTION: Primary thyroid leiomyosarcoma is an extremely rare soft tissue sarcoma, characterized by high malignancy and poor prognosis. Currently, only 13 cases of primary thyroid leiomyosarcoma have been described in the medical literature (limited to English). CASE PRESENTATION: A 76-year-old female presented with a giant neck mass. Physical examination revealed a large, firm mass in the left thyroid gland. No symptoms such as hoarseness or dysphagia were noted at the time of presentation. The patient underwent unilateral thyroidectomy and cervical lymph node dissection. CLINICAL DISCUSSION: Pathologic findings revealed a low-grade sarcoma with spindle-shaped tumor cells in an interwoven, sheet-like distribution. Immunohistochemistry showed positivity for desmin, SMMHC, STAT6, CK19, and Galectin3, but negativity for S-100, MyoD1, CD34, CK (AE1/AE3), CD117, and CD56. The findings were consistent with thyroid leiomyosarcoma. CONCLUSION: The treatment of primary thyroid LMS presents challenges due to its atypical symptoms and high malignance, highlighting the imperative for further exploration of therapeutic strategies to improve the outcomes.

2.
Schizophr Res ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38729789

RESUMO

BACKGROUND: Schizophrenia (SZ) is characterized by disconnected cerebral networks. Recent studies have shown that functional connectivity between the cerebellar dorsal dentate nucleus (dDN) and cerebrum is correlated with psychotic symptoms, and processing speed in SZ patients. Dynamic effective connectivity (dEC) is a reliable indicator of brain functional status. However, the dEC between the dDN and cerebrum in patients with SZ remains largely unknown. METHODS: Resting-state functional MRI data, symptom severity, and cognitive performance were collected from 74 SZ patients and 53 healthy controls (HC). Granger causality analysis and sliding time window methods were used to calculate dDN-based dEC maps for all subjects, and k-means clustering was performed to obtain several dEC states. Finally, between-group differences in dynamic effective connectivity variability (dECV) and clinical correlations were obtained using two-sample t-tests and correlation analysis. RESULTS: We detected four dEC states from the cerebrum to the right dDN (IN states) and three dEC states from the right dDN to the cerebrum (OUT states), with SZ group having fewer transitions in the OUT states. SZ group had increased dECV from the right dDN to the right middle frontal gyrus (MFG) and left lingual gyrus (LG). Correlations were found between the dECV from the right dDN to the right MFG and symptom severity and between the dECV from the right dDN to the left LG and working memory performance. CONCLUSIONS: This study reveals a dynamic causal relationship between cerebellar dDN and the cerebrum in SZ and provides new evidence for the involvement of cerebellar neural circuits in neurocognitive functions in SZ.

3.
ACS Chem Neurosci ; 15(10): 2018-2027, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38701380

RESUMO

In silico modeling was applied to study the efficiency of two ligands, namely, UCB-J and UCB-F, to bind to isoforms of the synaptic vesicle glycoprotein 2 (SV2) that are involved in the regulation of synaptic function in the nerve terminals, with the ultimate goal to understand the selectivity of the interaction between UCB-J and UCB-F to different isoforms of SV2. Docking and large-scale molecular dynamics simulations were carried out to unravel various binding patterns, types of interactions, and binding free energies, covering hydrogen bonding and nonspecific hydrophobic interactions, water bridge, π-π, and cation-π interactions. The overall preference for bonding types of UCB-J and UCB-F with particular residues in the protein pockets can be disclosed in detail. A unique interaction fingerprint, namely, hydrogen bonding with additional cation-π interaction with the pyridine moiety of UCB-J, could be established as an explanation for its high selectivity over the SV2 isoform A (SV2A). Other molecular details, primarily referring to the presence of π-π interactions and hydrogen bonding, could also be analyzed as sources of selectivity of the UCB-F tracer for the three isoforms. The simulations provide atomic details to support future development of new selective tracers targeting synaptic vesicle glycoproteins and their associated diseases.


Assuntos
Glicoproteínas de Membrana , Simulação de Dinâmica Molecular , Proteínas do Tecido Nervoso , Isoformas de Proteínas , Ligantes , Isoformas de Proteínas/química , Isoformas de Proteínas/metabolismo , Proteínas do Tecido Nervoso/química , Proteínas do Tecido Nervoso/metabolismo , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/química , Humanos , Ligação de Hidrogênio , Ligação Proteica/fisiologia , Simulação de Acoplamento Molecular/métodos , Vesículas Sinápticas/metabolismo
4.
Bioorg Chem ; 147: 107412, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38696845

RESUMO

The development of novel topoisomerase I (TOP1) inhibitors is crucial for overcoming the drawbacks and limitations of current TOP1 poisons. Here, we identified two potential TOP1 inhibitors, namely, FTY720 (a sphingosine 1-phosphate antagonist) and COH29 (a ribonucleotide reductase inhibitor), through experimental screening of known active compounds. Biological experiments verified that FTY720 and COH29 were nonintercalative TOP1 catalytic inhibitors that did not induce the formation of DNA-TOP1 covalent complexes. Molecular docking revealed that FTY720 and COH29 interacted favorably with TOP1. Molecular dynamics simulations revealed that FTY720 and COH29 could affect the catalytic domain of TOP1, thus resulting in altered DNA-binding cavity size. The alanine scanning and interaction entropy identified Arg536 as a hotspot residue. In addition, the bioinformatics analysis predicted that FTY720 and COH29 could be effective in treating malignant breast tumors. Biological experiments verified their antitumor activities using MCF-7 breast cancer cells. Their combinatory effects with TOP1 poisons were also investigated. Further, FTY720 and COH29 were found to cause less DNA damage compared with TOP1 poisons. The findings provide reliable lead compounds for the development of novel TOP1 catalytic inhibitors and offer new insights into the potential clinical applications of FTY720 and COH29 in targeting TOP1.


Assuntos
Antineoplásicos , DNA Topoisomerases Tipo I , Cloridrato de Fingolimode , Simulação de Acoplamento Molecular , Inibidores da Topoisomerase I , Humanos , Cloridrato de Fingolimode/farmacologia , Cloridrato de Fingolimode/química , Cloridrato de Fingolimode/síntese química , DNA Topoisomerases Tipo I/metabolismo , DNA Topoisomerases Tipo I/química , Inibidores da Topoisomerase I/farmacologia , Inibidores da Topoisomerase I/química , Inibidores da Topoisomerase I/síntese química , Estrutura Molecular , Relação Estrutura-Atividade , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Proliferação de Células/efeitos dos fármacos , Simulação de Dinâmica Molecular , Células MCF-7
5.
J Nanobiotechnology ; 22(1): 257, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38755645

RESUMO

Imperceptible examination and unideal treatment effect are still intractable difficulties for the clinical treatment of pancreatic ductal adenocarcinoma (PDAC). At present, despite 5-fluorouracil (5-FU), as a clinical first-line FOLFIRINOX chemo-drug, has achieved significant therapeutic effects. Nevertheless, these unavoidable factors such as low solubility, lack of biological specificity and easy to induce immunosuppressive surroundings formation, severely limit their treatment in PDAC. As an important source of energy for many tumor cells, tryptophan (Trp), is easily degraded to kynurenine (Kyn) by indolamine 2,3- dioxygenase 1 (IDO1), which activates the axis of Kyn-AHR to form special suppressive immune microenvironment that promotes tumor growth and metastasis. However, our research findings that 5-FU can induce effectively immunogenic cell death (ICD) to further treat tumor by activating immune systems, while the secretion of interferon-γ (IFN-γ) re-induce the Kyn-AHR axis activation, leading to poor treatment efficiency. Therefore, a metal matrix protease-2 (MMP-2) and endogenous GSH dual-responsive liposomal-based nanovesicle, co-loading with 5-FU (anti-cancer drug) and NLG919 (IDO1 inhibitor), was constructed (named as ENP919@5-FU). The multifunctional ENP919@5-FU can effectively reshape the tumor immunosuppression microenvironment to enhance the effect of chemoimmunotherapy, thereby effectively inhibiting cancer growth. Mechanistically, PDAC with high expression of MMP-2 will propel the as-prepared nanovesicle to dwell in tumor region via shedding PEG on the nanovesicle surface, effectively enhancing tumor uptake. Subsequently, the S-S bond containing nanovesicle was cut via high endogenous GSH, leading to the continued release of 5-FU and NLG919, thereby enabling circulating chemoimmunotherapy to effectively cause tumor ablation. Moreover, the combination of ENP919@5-FU and PD-L1 antibody (αPD-L1) showed a synergistic anti-tumor effect on the PDAC model with abdominal cavity metastasis. Collectively, ENP919@5-FU nanovesicle, as a PDAC treatment strategy, showed excellent antitumor efficacy by remodeling tumor microenvironment to circulate tumor chemoimmunotherapy amplification, which has promising potential in a precision medicine approach.


Assuntos
Carcinoma Ductal Pancreático , Fluoruracila , Imunoterapia , Microambiente Tumoral , Microambiente Tumoral/efeitos dos fármacos , Animais , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Camundongos , Humanos , Imunoterapia/métodos , Linhagem Celular Tumoral , Carcinoma Ductal Pancreático/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Metaloproteinase 2 da Matriz/metabolismo , Lipossomos/química , Cinurenina/metabolismo , Interferon gama/metabolismo , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/química , Oxaliplatina/farmacologia , Oxaliplatina/uso terapêutico
6.
Biochem Biophys Res Commun ; 720: 150077, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38759303

RESUMO

Hericenone C is one of the most abundant secondary metabolites derived from Hericium erinaceus, under investigation for medicinal properties. Here, we report that Hericenone C inhibits the second phase of formalin-induced nociceptive behavior in mice. As the second phase is involved in inflammation, in a mechanistic analysis on cultured cells targeting NF-κB response element (NRE): luciferase (Luc)-expressing cells, lipopolysaccharide (LPS)-induced NRE::Luc luciferase activity was found to be significantly inhibited by Hericenone C. Phosphorylation of p65, which is involved in the inflammatory responses of the NF-κB signaling pathway, was also induced by LPS and significantly reduced by Hericenone C. Additionally, in mice, the number of CD11c-positive cells increased in the paw during the peak of the second phase of the formalin test, which decreased upon Hericenone C intake. Our findings confirm the possibility of Hericenone C as a novel therapeutic target for pain-associated inflammation.

7.
Nanotechnology ; 35(31)2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38684153

RESUMO

In materials science, the impact of density on a material's capabilities is profound. Conventional sintering requires high temperatures and is energy-demanding, propelling the pursuit of less intensive, low-temperature densification methods. Electric field-assisted sintering has recently gained attention for its simplicity and effectiveness, offering a new frontier in low-temperature densification. In this study, dense bulk materials were produced by subjecting monophasic Ag2Se powders to electric field-assisted sintering, where a direct current with an average value of 4 A was applied, achieving a peak temperature of 344 K. The novel low-temperature densification mechanism unfolds thus: nanoscale silver protrusions, stimulated by electrical current, engage in a dissociative adsorption reaction with the ambient saturated selenium vapor. This process swiftly engenders the formation of fresh silver selenide (Ag2Se) compounds, initiating nucleation and subsequent growth. Consecutively, these compounds seamlessly occupy and expand, perpetually bridging the interstices amidst the powders. In a scant 8 s, the density swiftly surpassed 99%, yielding a bulk material that exhibited aZTvalue of 1.07 at 390 K. This investigation not only attains an unparalleled density at low temperatures but also charts a pioneering course for material densification in such conditions.

8.
ACS Appl Mater Interfaces ; 16(17): 22189-22196, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38651521

RESUMO

Understanding mass transfer mechanisms is vital for developing new material synthesis and densification technologies. Ion transport, serving both mass and charge transfer, is essential for the rapid preparation of high-performance fast ionic conductor thermoelectric materials like Zn4Sb3 and Cu2Q (Q = S, Se). In the case of dual-cation fast ion conductor materials like CuAgSe, exploring the relationship between cation transport becomes pertinent. In this study, copper (Cu) and selenium (Se) undergo a reaction in the presence of an electric field (∼15 A), resulting in the formation of the CuSe compound. Subsequent to this initial reaction, a subsequent thermal environment facilitates the interaction among Cu, CuSe, and Ag2Se, culminating in the rapid formation and densification of CuAgSe (with a relative density exceeding 99%) in just 30 s. Evidently, the diffusion of copper ions substantiates a pivotal role in facilitating mass transfer. As a result, CuAg1+xSe samples with different silver contents (x = 0.01, 0.02, 0.03, 0.04 and 0.05) can effectively inhibit cation vacancy, and introduce highly ordered Ag nanotwins to enhance the electrical transport performance. For CuAg1.04Se, a peak ZT value of 1.0 can be achieved at 673 K, which is comparable to the literatures. This work will guide the future electric field-assisted rapid mass transfer of materials.

9.
Mol Plant Pathol ; 25(4): e13447, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38561315

RESUMO

Genetic engineering using negative regulators of plant immunity has the potential to provide a huge impetus in agricultural biotechnology to achieve a higher degree of disease resistance without reducing yield. Type 2C protein phosphatases (PP2Cs) represent the largest group of protein phosphatases in plants, with a high potential for negative regulatory functions by blocking the transmission of defence signals through dephosphorylation. Here, we established a PP2C functional protoplast screen using pFRK1::luciferase as a reporter and found that 14 of 56 PP2Cs significantly inhibited the immune response induced by flg22. To verify the reliability of the system, a previously reported MAPK3/4/6-interacting protein phosphatase, PP2C5, was used; it was confirmed to be a negative regulator of PAMP-triggered immunity (PTI). We further identified PP2C15 as an interacting partner of BRI1-associated receptor kinase 1 (BAK1), which is the most well-known co-receptor of plasma membrane-localized pattern recognition receptors (PRRs), and a central component of PTI. PP2C15 dephosphorylates BAK1 and negatively regulates BAK1-mediated PTI responses such as MAPK3/4/6 activation, defence gene expression, reactive oxygen species bursts, stomatal immunity, callose deposition, and pathogen resistance. Although plant growth and 1000-seed weight of pp2c15 mutants were reduced compared to those of wild-type plants, pp2c5 mutants did not show any adverse effects. Thus, our findings strengthen the understanding of the mechanism by which PP2C family members negatively regulate plant immunity at multiple levels and indicate a possible approach to enhance plant resistance by eliminating specific PP2Cs without affecting plant growth and yield.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Reprodutibilidade dos Testes , Fosfoproteínas Fosfatases/genética , Fosfoproteínas Fosfatases/metabolismo , Fosfoproteínas Fosfatases/farmacologia , Imunidade Vegetal/fisiologia , Regulação da Expressão Gênica de Plantas , Proteínas Quinases/genética , Proteínas Quinases/metabolismo
10.
Polymers (Basel) ; 16(7)2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38611242

RESUMO

The design of high-performance polyimide (PI) films and understanding the relationship of the structure-dielectric property are of great significance in the field of the microelectronics industry, but are challenging. Herein, we describe the first work to construct a series of novel tert-butyl PI films (denoted as PI-1, PI-2, PI-3, and PI-4) based on a low-temperature polymerization strategy, which employed tetracarboxylic dianhydride (pyromellitic anhydride, 3,3',4,4'-biphenyl tetracarboxylic anhydride, 4,4'-diphenyl ether dianhydride, and 3,3',4,4'-benzophenone tetracarboxylic anhydride) and 4,4'-diamino-3,5-ditert butyl biphenyl ether as monomers. The results indicate that introducing tert-butyl branches in the main chain of PIs can enhance the free volume of the molecular chain and reduce the interaction between molecular chains of PI, resulting in a low dielectric constant. Particularly, the optimized PI-4 exhibits an excellent comprehensive performance with a high (5) wt% loss temperature (454 °C), tensile strength (117.40 MPa), and maximum hydrophobic angle (80.16°), and a low dielectric constant (2.90), which outperforms most of the results reported to date.

11.
J Psychiatr Res ; 173: 115-123, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38520845

RESUMO

BACKGROUND: Evidence indicates that patients with schizophrenia (SZ) experience significant changes in their functional connectivity during antipsychotic treatment. Despite previous reports of changes in brain network degree centrality (DC) in patients with schizophrenia, the relationship between brain DC changes and neurocognitive improvement in patients with SZ after antipsychotic treatment remains elusive. METHODS: A total of 74 patients with acute episodes of chronic SZ and 53 age- and sex-matched healthy controls were recruited. The Positive and Negative Syndrome Scale (PANSS), Symbol Digit Modalities Test, digital span test (DST), and verbal fluency test were used to evaluate the clinical symptoms and cognitive performance of the patients with SZ. Patients with SZ were treated with antipsychotics for six weeks starting at baseline and underwent MRI and clinical interviews at baseline and after six weeks, respectively. We then divided the patients with SZ into responding (RS) and non-responding (NRS) groups based on the PANSS scores (reduction rate of PANSS ≥50%). DC was calculated and analyzed to determine its correlation with clinical symptoms and cognitive performance. RESULTS: After antipsychotic treatment, the patients with SZ showed significant improvements in clinical symptoms, semantic fluency performance. Correlation analysis revealed that the degree of DC increase in the left anterior inferior parietal lobe (aIPL) after treatment was negatively correlated with changes in the excitement score (r = -0.256, p = 0.048, adjusted p = 0.080), but this correlation failed the multiple test correction. Patients with SZ showed a significant negative correlation between DC values in the left aIPL and DST scores after treatment, which was not observed at the baseline (r = -0.359, p = 0.005, adjusted p = 0.047). In addition, we did not find a significant difference in DC between the RS and NRS groups, neither at baseline nor after treatment. CONCLUSIONS: The results suggested that DC changes in patients with SZ after antipsychotic treatment are correlated with neurocognitive performance. Our findings provide new insights into the neuropathological mechanisms underlying antipsychotic treatment of SZ.


Assuntos
Antipsicóticos , Esquizofrenia , Humanos , Esquizofrenia/complicações , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/tratamento farmacológico , Antipsicóticos/uso terapêutico , Imageamento por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Estudos Longitudinais
13.
ACS Appl Mater Interfaces ; 16(13): 16505-16514, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38527233

RESUMO

The micro thermoelectric device (m-TED) boasts features such as adjustable volume, straightforward structure, and precise, rapid temperature control, positioning it as the only current solution for managing the temperature of microelectronic systems. It is extensively utilized in 5G optical modules, laser lidars, and infrared detection. Nevertheless, as the size of the m-TED diminishes, the growing proportion of interface damages the device's operational reliability, constraining the advancement of the m-TED. In this study, we used commercially available bismuth telluride materials to construct the m-TED. The device's reliability was tested under various temperatures: -40, 85, 125, and 150 °C. By deconstructing and analyzing the devices that failed during the tests, we discovered that the primary cause of device failure was the degradation of the solder layer. Moreover, we demonstrated that encapsulating the device with polydimethylsiloxane (PDMS) could effectively delay the deterioration of its performance. This study sparks new insights into the service reliability of m-TEDs and paves the way for further optimizing device interface design and enhancing the device manufacturing process.

14.
Small ; : e2401153, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38501763

RESUMO

Lithium-sulfur batteries are recognized as the next generation of high-specific energy secondary batteries owing to their satisfactory theoretical specific capacity and energy density. However, their commercial application is greatly limited by a series of problems, including disordered migration behavior, sluggish redox kinetics, and the serious shuttle effect of lithium polysulfides. One of the most efficient approaches to physically limit the shuttle effect is the rational design of a hollow framework as sulfur host. However, the influence of the hollow structure on the interlayers has not been clearly reported. In this study, the Mo2 C/C catalysts with hollow(H-Mo2 C/C) and solid(S-Mo2 C/C) frameworks are rationally designed to explore the dependence of the hollow structure on the interlayer or sulfur host. In contrast to the physical limitations of the hollow framework as host, the hollow structure of the interlayer inhibited lithium-ion diffusion, resulting in poor electrochemical properties at high current densities. Based on the superiority of the various frameworks, the H-Mo2 C/C@S | S-Mo2 C/C@PP | Li cells are assembled and displayed excellent electrochemical performance. This work re-examines the design requirements and principles of catalyst frameworks in different battery units.

15.
Med Biol Eng Comput ; 62(6): 1689-1701, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38342784

RESUMO

Motor imagery (MI) paradigms have been widely used in neural rehabilitation and drowsiness state assessment. The progress in brain-computer interface (BCI) technology has emphasized the importance of accurately and efficiently detecting motor imagery intentions from electroencephalogram (EEG). Despite the recent breakthroughs made in developing EEG-based algorithms for decoding MI, the accuracy and efficiency of these models remain limited by technical challenges posed by cross-subject heterogeneity in EEG data processing and the scarcity of EEG data for training. Inspired by the optimal transport theory, this study aims to develop a novel three-stage transfer learning (TSTL) method, which uses the existing labeled data from a source domain to improve classification performance on an unlabeled target domain. Notably, the proposed method comprises three components, namely, the Riemannian tangent space mapping (RTSM), source domain transformer (SDT), and optimal subspace mapping (OSM). The RTSM maps a symmetric positive definite matrix from the Riemannian space to the tangent space to minimize the marginal probability distribution drift. The SDT transforms the source domain to a target domain by finding the optimal transport mapping matrix to reduce the joint probability distribution differences. The OSM finally maps the transformed source domain and original target domain to the same subspace to further mitigate the distribution discrepancy. The performance of the proposed method was validated on two public BCI datasets, and the average accuracy of the algorithm on two datasets was 72.24% and 69.29%. Our results demonstrated the improved performance of EEG-based MI detection in comparison with state-of-the-art algorithms.


Assuntos
Algoritmos , Interfaces Cérebro-Computador , Eletroencefalografia , Humanos , Eletroencefalografia/métodos , Aprendizado de Máquina , Processamento de Sinais Assistido por Computador , Imaginação/fisiologia
16.
Int J Mol Sci ; 25(3)2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38339125

RESUMO

The leading cause of death for patients with Duchenne muscular dystrophy (DMD), a progressive muscle disease, is heart failure. Prostaglandin (PG) D2, a physiologically active fatty acid, is synthesized from the precursor PGH2 by hematopoietic prostaglandin D synthase (HPGDS). Using a DMD animal model (mdx mice), we previously found that HPGDS expression is increased not only in injured muscle but also in the heart. Moreover, HPGDS inhibitors can slow the progression of muscle injury and cardiomyopathy. However, the location of HPGDS in the heart is still unknown. Thus, this study investigated HPGDS expression in autopsy myocardial samples from DMD patients. We confirmed the presence of fibrosis, a characteristic phenotype of DMD, in the autopsy myocardial sections. Additionally, HPGDS was expressed in mast cells, pericytes, and myeloid cells of the myocardial specimens but not in the myocardium. Compared with the non-DMD group, the DMD group showed increased HPGDS expression in mast cells and pericytes. Our findings confirm the possibility of using HPGDS inhibitor therapy to suppress PGD2 production to treat skeletal muscle disorders and cardiomyopathy. It thus provides significant insights for developing therapeutic drugs for DMD.


Assuntos
Cardiomiopatias , Oxirredutases Intramoleculares , Lipocalinas , Distrofia Muscular de Duchenne , Animais , Humanos , Camundongos , Cardiomiopatias/etiologia , Cardiomiopatias/metabolismo , Modelos Animais de Doenças , Mastócitos/metabolismo , Camundongos Endogâmicos mdx , Músculo Esquelético/metabolismo , Distrofia Muscular de Duchenne/genética , Miocárdio/metabolismo , Pericitos/metabolismo
17.
Artigo em Inglês | MEDLINE | ID: mdl-38289442

RESUMO

Time-of-death extrapolation has always been one of the most important issues in forensic practice. For a complicated case in which a corpse is destroyed with little evidence, judging the time of death of the deceased is a major challenge, which also enables criminals to escape legal sanctions. To find a method to roughly judge the time of death of a corpse with only a small amount of skin tissue, in this study, we established an early death model by using mice; furthermore, the postmortem interval was estimated by determining the protein and mRNA levels of Bax and Bcl-2 in the skin. In this process, 0 h after death was used as the control group, and the expression levels of Bax and Caspase-3 reached the maximum value at 8-12 h, while Bcl-2, as an inhibitor of apoptosis protein, peaked after 24 h. The mRNA expression levels of related proteins in postmortem skin tissues were also different. The results of these data indicate that the protein and mRNA levels of Bax and Bcl-2 in the skin have potential application in early time-of-death estimation.

18.
Clin Nucl Med ; 49(3): e137-e138, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38271250

RESUMO

ABSTRACT: Hemosiderosis is a chronic condition characterized by abnormal iron accumulation in tissues. In a PET scan of a 37-year-old woman, we observed an irregular distribution of 68 Ga-DOTATATE in the liver and spleen. Specifically, 68 Ga-DOTATATE appeared to be concentrated primarily in the peripheral regions of these organs, creating a distinctive "shell-like" appearance. This peculiar pattern may be attributed to the substantial accumulation of hemosiderin in the liver and spleen.


Assuntos
Radioisótopos de Gálio , Hemocromatose , Tumores Neuroendócrinos , Compostos Organometálicos , Cintilografia , Feminino , Humanos , Adulto , Baço/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Fígado/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada
19.
Artigo em Inglês | MEDLINE | ID: mdl-37977490

RESUMO

Glyceroglycolipids are the primary thylakoid membrane lipids in cyanobacteria. Their diverse bioactivities have led to extensive utilization in the biomedical industry. In this study, we elucidated the role of ERA (E. coli Ras-like protein) in augmenting glyceroglycolipid synthesis and bolstering stress resilience in Synechococcus elongatus PCC 7942 during phosphate starvation. Notably, the ERA overexpression strain (ERA OE) outperformed the wild-type (WT) strain under phosphate-starved conditions, displaying an average 13.9 % increase in biomass over WT during the entire growth period, peaking at 0.185 g L-1 of dry cell weight on day 6. Lipidomic analysis using UHPLC-MS/MS techniques revealed that ERA OE exhibited a higher total glyceroglycolipid content compared to WT under phosphate starvation, representing a 7.95 % increase over WT and constituting a maximum of 5.07 % of dry cell weight on day 6. Transcriptomic analysis identified a significant up-regulation of the gldA gene (encoding glycerol dehydrogenase) involved in glycerolipid metabolism due to overexpression of ERA during phosphate starvation. These findings suggest a potential mechanism by which ERA regulates glyceroglycolipid synthesis through the up-regulation of GldA, thereby enhancing phosphate starvation tolerance in S. elongatus PCC 7942. Furthermore, lipidomic analysis revealed that ERA facilitated the production of glyceroglycolipid molecules containing C16:1 and C18:1 fatty acids. Additionally, ERA redirected lipid flux and promoted glyceroglycolipid accumulation while attenuating triacylglycerol production under phosphate starvation. This study represents the first demonstration of pivotal role of ERA in enhancing glyceroglycolipid synthesis and phosphate starvation tolerance in cyanobacteria, offering new insights into the effective utilization of glyceroglycolipids in various applications.


Assuntos
Fosfatos , Synechococcus , Fosfatos/metabolismo , Escherichia coli/metabolismo , Espectrometria de Massas em Tandem , Synechococcus/genética , Synechococcus/metabolismo
20.
BMC Psychiatry ; 23(1): 832, 2023 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-37957613

RESUMO

BACKGROUND: Major depressive disorder (MDD) has a high incidence and an unknown mechanism. There are no objective and sensitive indicators for clinical diagnosis. OBJECTIVE: This study explored specific electrophysiological indicators and their role in the clinical diagnosis of MDD using machine learning. METHODS: Forty first-episode and drug-naïve patients with MDD and forty healthy controls (HCs) were recruited. EEG data were collected from all subjects in the resting state with eyes closed for 10 min. The severity of MDD was assessed by the Hamilton Depression Rating Scale (HAMD-17). Machine learning analysis was used to identify the patients with MDD. RESULTS: Compared to the HC group, the relative power of the low delta and theta bands was significantly higher in the right occipital region, and the relative power of the alpha band in the entire posterior occipital region was significantly lower in the MDD group. In the MDD group, the alpha band scalp functional connectivity was overall lower, while the scalp functional connectivity in the gamma band was significantly higher than that in the HC group. In the feature set of the relative power of the ROI in each band, the highest accuracy of 88.2% was achieved using the KNN classifier while using PCA feature selection. In the explanatory model using SHAP values, the top-ranking influence feature is the relative power of the alpha band in the left parietal region. CONCLUSIONS: Our findings reveal that the abnormal EEG neural oscillations may reflect an imbalance of excitation, inhibition and hyperactivity in the cerebral cortex in first-episode and drug-naïve patients with MDD. The relative power of the alpha band in the left parietal region is expected to be an objective electrophysiological indicator of MDD.


Assuntos
Transtorno Depressivo Maior , Humanos , Transtorno Depressivo Maior/diagnóstico , Córtex Cerebral , Lobo Parietal , Lobo Occipital , Eletroencefalografia , Imageamento por Ressonância Magnética
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