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1.
Value Health Reg Issues ; 44: 101029, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39094426

RESUMO

OBJECTIVES: This study analyzed the basic condition and the influencing factors of hospitalization costs of patients with gastric cancer in Shanghai from 2014 to 2021, so as to provide a scientific reference for promoting the reform of the medical and healthcare system. METHODS: The study data were obtained from the electronic medical record system of Shanghai Hospital. The grey relational analysis was applied to analyze the correlation strength of various expenses with hospitalization costs. The structural equation modeling was constructed to analyze the influences of factors on the hospitalization expenses, as well as the relationship between each factor. RESULTS: A total of 23 335 study subjects were included. The results of grey relational analysis showed that the total cost of drugs had the strongest correlation with hospitalization expenses, followed by material expenses and surgery cost, whereas those of others were lower. The results of the structural equation modeling showed that age had the greatest influence on hospitalization expenses with a path coefficient of 0.618. Other influencing factors included surgery history, length of stay, hospital level, gender, and medical insurance. CONCLUSIONS: The total cost of drugs had the strongest correlation with hospitalization expenses. Factors such as gender, age, and hospital level all affect the hospitalization expenses. In the future, it is necessary to take further measures to control the cost of drugs and constantly optimize the structure of hospitalization costs. Meanwhile, the reform of the medical and healthcare system should be deepened to reasonably regulate the medical behaviors and reduce the financial burden of patients.

2.
Org Lett ; 26(29): 6076-6080, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-38996187

RESUMO

We present a catalytic strategy for converting lignin into various pharmaceutical intermediates based on a highly selective lignin depolymerization method and a green benzylic oxidation method employing O2. Selective depolymerization of lignin first afforded 4-ethylphenol, which then efficiently generates several pharmaceutical intermediates with a simple 5-step process, resulting in substantial economic benefits. The study provides an innovative solution for the efficient utilization of lignin and the green acquisition of pharmaceutical intermediates.

3.
Sci Adv ; 10(29): eado2118, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39018408

RESUMO

We conduct in situ tensile straining experiments to investigate the role of hydrogen and slip in crack initiation in nickel-based alloy 725. Our experiments reveal no tendency for hydrogen to enhance localized slip and no necessity of slip for crack initiation. We use electrochemical charging to introduce hydrogen into samples, melt extraction to measure hydrogen content, and digital image correlation to analyze localized plastic strains during in situ tensile tests in a scanning electron microscope. Cracks initiate both in regions with and without nearby localized slip. Moreover, the fraction of cracks initiating with no nearby slip is greater at higher hydrogen content. Slip-assisted crack initiation generally occurs at locations where intergranular slip is arrested, especially at intersections of slipping coherent twin boundaries with thin twin lamellae. Cracks that initiate without nearby slip occur at a wider variety of microstructural features, including inclusions, triple junctions, and surface flaws.

4.
Food Res Int ; 191: 114717, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39059914

RESUMO

To reveal the interaction of oxidative stress and protein S-nitrosylation on mitochondrial pathway apoptosis and tenderness development in postmortem yak meat. Herein, we selected yak longissimus dorsi muscle as the research object and treated hydrogen peroxide (H2O2) with S-nitrosoglutathione agent (GSNO) as well as Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME) in mixed injections with 0.9 % saline as a control group, followed by incubation at 4 °C for 12, 24, 72, 120 and 168 h. Results showed that this interaction significantly increased mitochondrial ROS and NO content (P < 0.05) while weakening the antioxidant capacity of GSH and TRX redox response systems or accelerating the Ca2+ release process, leading to mitochondrial functional impairment and increased apoptosis rate. Notably, the H2O2 + L-NAME group showed more pronounced apoptosis. Hence, we suggest that the interaction between oxidative stress and protein S-nitrosylation could positively regulate yak meat tenderization.


Assuntos
Apoptose , Peróxido de Hidrogênio , Estresse Oxidativo , Animais , Apoptose/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Bovinos , Peróxido de Hidrogênio/metabolismo , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , NG-Nitroarginina Metil Éster/farmacologia , Músculo Esquelético/metabolismo , Músculo Esquelético/efeitos dos fármacos , Óxido Nítrico/metabolismo , Carne/análise , Mudanças Depois da Morte , Espécies Reativas de Oxigênio/metabolismo , S-Nitrosoglutationa/farmacologia , S-Nitrosoglutationa/metabolismo , Antioxidantes/metabolismo , Antioxidantes/farmacologia
5.
Int J Biol Macromol ; 277(Pt 1): 133596, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38960269

RESUMO

In order to investigate the effect of glucono-δ-lactone (GDL) and different salt ions (Na+ and Ca2+) induction on the cold-set gels of bovine serum albumin (BSA)-arabinoxylan (AX), the gel properties and structure of BSA-AX cold-set gels were evaluated by analyzing the gel strength, water-holding capacity, thermal properties, and Fourier Transform Infrared (FTIR) spectra. It was shown that the best gel strength (109.15 g) was obtained when the ratio of BSA to AX was 15:1. The addition of 1 % GDL significantly improved the water-holding capacity, gel strength and thermal stability of the cold-set gels (p < 0.05), and the microstructure was smoother. Low concentrations of Na+ (3 mM) and Ca2+ (6 mM) significantly enhanced the hydrophobic interaction and hydrogen bonding between BSA and AX after acid induction, and the Na+-induced formation of a denser microstructure with a higher water-holding capacity (75.51 %). However, the excess salt ions disrupted the stable network structure of the cold-set gels and reduced their thermal stability and crystalline structure. The results of this study contribute to the understanding of the interactions between BSA and AX induced by GDL and salt ions, and provide a basis for designing hydrogels with different properties.

6.
Viruses ; 16(6)2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38932184

RESUMO

Endogenous retroviruses (ERVs) are related to long terminal repeat (LTR) retrotransposons, comprising gene sequences of exogenous retroviruses integrated into the host genome and inherited according to Mendelian law. They are considered to have contributed greatly to the evolution of host genome structure and function. We previously characterized HERV-K HML-9 in the human genome. However, the biological function of this type of element in the genome of the chimpanzee, which is the closest living relative of humans, largely remains elusive. Therefore, the current study aims to characterize HML-9 in the chimpanzee genome and to compare the results with those in the human genome. Firstly, we report the distribution and genetic structural characterization of the 26 proviral elements and 38 solo LTR elements of HML-9 in the chimpanzee genome. The results showed that the distribution of these elements displayed a non-random integration pattern, and only six elements maintained a relatively complete structure. Then, we analyze their phylogeny and reveal that the identified elements all cluster together with HML-9 references and with those identified in the human genome. The HML-9 integration time was estimated based on the 2-LTR approach, and the results showed that HML-9 elements were integrated into the chimpanzee genome between 14 and 36 million years ago and into the human genome between 18 and 49 mya. In addition, conserved motifs, cis-regulatory regions, and enriched PBS sequence features in the chimpanzee genome were predicted based on bioinformatics. The results show that pathways significantly enriched for ERV LTR-regulated genes found in the chimpanzee genome are closely associated with disease development, including neurological and neurodevelopmental psychiatric disorders. In summary, the identification, characterization, and genomics of HML-9 presented here not only contribute to our understanding of the role of ERVs in primate evolution but also to our understanding of their biofunctional significance.


Assuntos
Retrovirus Endógenos , Evolução Molecular , Genoma , Pan troglodytes , Filogenia , Sequências Repetidas Terminais , Animais , Retrovirus Endógenos/genética , Humanos , Genoma Humano , Provírus/genética , Integração Viral , Retroelementos
7.
Foods ; 13(10)2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38790806

RESUMO

The aim of this study is to produce a biodegradable food packaging material that reduces environmental pollution and protects food safety. The effects of total solids content, substrate ratio, polyphenol content, and magnetic stirring time on bovine bone gelatin/sodium carboxymethylcellulose nanoemulsion (BBG/SCMC-NE) were investigated using particle size, PDI, turbidity, rheological properties, and zeta potential as evaluation indexes. The micro, structural, antioxidant, encapsulation, and release properties were characterized after deriving its optimal preparation process. The results showed that the nanoemulsion was optimally prepared with a total solids content of 2%, a substrate ratio of 9:1, a polyphenol content of 0.2%, and a magnetic stirring time of 60 min. SEM showed that the nanoemulsion showed a dense and uniform reticulated structure. FTIR and XRD results showed that covalent cross-linking of proteins and polysaccharides altered the structure of gelatin molecular chains to a more compact form but did not change its semi-crystalline structure. DSC showed that the 9:1 BBG/SCMC-NE had a higher thermal denaturation temperature and greater thermal stability, and its DPPH scavenging rate could reach 79.25% and encapsulation rate up to 90.88%, with excellent slow-release performance. The results of the study provide basic guidance for the preparation of stable active food packaging with excellent properties.

8.
Talanta ; 277: 126303, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38796929

RESUMO

The detection of antibiotics and pesticides are of great significance since their residues threaten the health of human beings by accumulation. However, most traditional solid chemical sensors are suffer from the limitations of low sensitivity and economic practicability because of the aggregating nature and unstable of solid sensors. Herein, a new luminescent sensor 1@PMMA (1, [(ZnL)·H2O]n (H2L = 5-(4-(pyridin-4-yl)benzamido)benzene-1,3-dioic acid); PMMA = poly(methyl methacrylate)) was successfully prepared. Notably, the polymer matrix provided the chemical protection for MOF particles. The as fabricated 1@PMMA was stable in milk, honey and egg as well as exhibited strong blue emission under ultraviolet light irradiation, which can act as luminescent probe for detecting antibiotics and pesticides. More interestingly, 1@PMMA exhibited visual, real-time and recyclable detection of antibiotics ornidazole (ODZ) and pesticides 2,6-dichloro-4-nitrobenzenamine (DCN) in real food samples. This work shows that the luminescent MOF-based mixed matrix membranes could be applied as good candidates for sensing analytes in practical application.


Assuntos
Antibacterianos , Contaminação de Alimentos , Estruturas Metalorgânicas , Praguicidas , Antibacterianos/análise , Estruturas Metalorgânicas/química , Praguicidas/análise , Contaminação de Alimentos/análise , Zinco/análise , Zinco/química , Polimetil Metacrilato/química , Leite/química , Medições Luminescentes/métodos , Mel/análise , Animais , Ovos/análise , Membranas Artificiais , Análise de Alimentos/métodos , Limite de Detecção
9.
Cell Death Differ ; 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38698061

RESUMO

Uterine luminal epithelia (LE), the first layer contacting with the blastocyst, acquire receptivity for normal embryo implantation. Besides the well-accepted transcriptional regulation dominated by ovarian estrogen and progesterone for receptivity establishment, the involvement of epigenetic mechanisms remains elusive. This study systematically profiles the transcriptome and genome-wide H3K27me3 distribution in the LE throughout the preimplantation. Combining genetic and pharmacological approaches targeting the PRC2 core enzyme Ezh1/2, we demonstrate that the defective remodeling of H3K27me3 in the preimplantation stage disrupts the differentiation of LE, and derails uterine receptivity, resulting in implantation failure. Specifically, crucial epithelial genes, Pgr, Gata2, and Sgk1, are transcriptionally silenced through de novo deposition of H3K27me3 for LE transformation, and their sustained expression in the absence of H3K27me3 synergistically confines the nuclear translocation of FOXO1. Further functional studies identify several actin-associated genes, including Arpin, Tmod1, and Pdlim2, as novel direct targets of H3K27me3. Their aberrantly elevated expression impedes the morphological remodeling of LE, a hindrance alleviated by treatment with cytochalasin D which depolymerizes F-actin. Collectively, this study uncovers a previously unappreciated epigenetic regulatory mechanism for the transcriptional silencing of key LE genes via H3K27me3, essential for LE differentiation and thus embryo implantation.

10.
PLoS One ; 19(5): e0301809, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38696412

RESUMO

The HIV-1 provirus mainly consists of internal coding region flanked by 1 long terminal repeats (LTRs) at each terminus. The LTRs play important roles in HIV-1 reverse transcription, integration, and transcription. However, despite of the significant study advances of the internal coding regions of HIV-1 by using definite reference classification, there are no systematic and phylogenetic classifications for HIV-1 5' LTRs, which hinders our elaboration on 5' LTR and a better understanding of the viral origin, spread and therapy. Here, by analyzing all available resources of 5' LTR sequences in public databases following 4 recognized principles for the reference classification, 83 representatives and 14 consensus sequences were identified as representatives of 2 groups, 6 subtypes, 6 sub-subtypes, and 9 CRFs. To test the reliability of the supplemented classification system, the constructed references were applied to identify the 5' LTR assignment of the 22 clinical isolates in China. The results revealed that 16 out of 22 tested strains showed a consistent subtype classification with the previous LTR-independent classification system. However, 6 strains, for which recombination events within 5' LTR were demonstrated, unexpectedly showed a different subtype classification, leading a significant change of binding sites for important transcription factors including SP1, p53, and NF-κB. The binding change of these transcriptional factors would probably affect the transcriptional activity of 5' LTR. This study supplemented a unified classification system for HIV-1 5' LTRs, which will facilitate HIV-1 characterization and be helpful for both basic and clinical research fields.


Assuntos
Repetição Terminal Longa de HIV , HIV-1 , Filogenia , HIV-1/genética , HIV-1/classificação , Repetição Terminal Longa de HIV/genética , Humanos , Sítios de Ligação
11.
Small ; : e2402168, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38757427

RESUMO

A metal-free nanocarbon with an eggshell structure is synthesized from chitosan (CS) and natural spherical graphite (NSG) as a cathode electrocatalyst for clean zinc-air batteries and fuel cells. It is developed using CS-derived carbons as an eggshell, covering NSG cores. The synthesis involves the in situ growth of CS on NSG, followed by ammonia-assisted pyrolysis for carbonization. The resulting catalyst displays a curved structure and completely coated NSG, showing superior oxygen reduction reaction (ORR) performance. In 1 M NaOH, the ORR half-wave potential reached 0.93 V, surpassing the commercial Pt/C catalyst by 50 mV. Furthermore, a zinc-air battery featuring the catalyst achieves a peak power density of 167 mW cm-2 with excellent stability, outperforming the Pt/C. The improved performance of the eggshell carbons can be attributed to the distorted energy band of the active sites in the form of N-C moieties. More importantly, the curved thin eggshells induce built-in electric fields that can promote electron redistribution to generate atomic charge waves around the N-C moieties on the carbon shells. As a result, the high positively charged and stable C+ sites adjacent to N atoms optimize the adsorption strength of oxygen molecules, thereby facilitating performance.

12.
Oncol Lett ; 28(1): 305, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38774454

RESUMO

Esculetin (Esc), a coumarin derivative and herbal medicinal compound used in traditional Chinese medicine, is extracted from Fraxinus chinensis. Esc has shown notable potential in the inhibition of proliferation, metastasis and cell cycle arrest in various cancer cell lines. The present review is based on research articles regarding Esc in the field of carcinoma, published between 2009 and 2023. These studies have unanimously demonstrated that Esc can effectively inhibit cancer cell proliferation through diverse mechanisms and modulate multiple signaling pathways, such as Wnt/ß-catenin, PI3K/Akt, MAPK and janus kinase/signal transducer and activator of transcription-3. In addition, the safety profile of Esc has been demonstrated in credible animal experiments, which has indicated Esc as an effective compound. Furthermore, the combination therapy of Esc with commonly used chemotherapeutic drugs holds great promise. The aim of the present review was to encourage further studies and applications of Esc in cancer therapy.

13.
Theor Appl Genet ; 137(5): 114, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38678513

RESUMO

KEY MESSAGE: Map-based cloning revealed that a mutation in a highly conserved amino acid of the CsGME gene encoding GDP-mannose 3,5-epimerase, causes the phenotype of little and wrinkled leaves in cucumbers. Leaf size is a critical determinant of plant architecture in cucumbers, yet only a few genes associated with this trait have been mapped or cloned. Here, we identified and characterized a mutant with little and wrinkled leaves, named lwl-1. Genetic analysis revealed that the phenotype of the lwl-1 was controlled by a single recessive gene. Through map-based cloning, the lwl-1 locus was narrowed down to a 12.22-kb region exclusively containing one fully annotated gene CsGME (CsaV3_2G004170). CsGME encodes GDP-mannose 3,5-epimerase, which is involved in the synthesis of ascorbic acid (ASA) and one of the components of pectin, RG-II. Whole-length sequencing of the 12.22 kb DNA fragment revealed the presence of only a non-synonymous mutation located in the sixth exon of CsGME in lwl-1, resulting in an amino acid alteration from Pro363 to Leu363. This mutation was unique among 118 inbred lines from cucumber natural populations. CsGME expression significantly reduced in various organs of lwl-1, accompanied by a significant decrease in ASA and pectin content in leaves. Both CsGME and Csgme proteins were localized to the cytoplasm. The mutant phenotype exhibited partial recovery after the application of exogenous boric acid. Silencing CsGME in cucumber through VIGS confirmed its role as the causal gene for lwl-1. Transcriptome profiling revealed that CsGME greatly affected the expression of genes related to the cell division process and cell plate formation. This study represents the first report to characterize and clone the CsGME in cucumber, indicating its crucial role in regulating leaf size and development.


Assuntos
Carboidratos Epimerases , Mapeamento Cromossômico , Cucumis sativus , Folhas de Planta , Ácido Ascórbico/metabolismo , Carboidratos Epimerases/genética , Carboidratos Epimerases/metabolismo , Clonagem Molecular , Cucumis sativus/genética , Cucumis sativus/crescimento & desenvolvimento , Cucumis sativus/enzimologia , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Genes Recessivos , Mutação , Fenótipo , Folhas de Planta/genética , Folhas de Planta/crescimento & desenvolvimento , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
14.
Eur J Med Chem ; 268: 116291, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38452728

RESUMO

Discoidin domain receptor 1 (DDR1) is a collagen-activated receptor tyrosine kinase (RTK) and plays pivotal roles in regulating cellular functions such as proliferation, differentiation, invasion, migration, and matrix remodeling. DDR1 is involved in the occurrence and progression of many human diseases, including cancer, fibrosis, and inflammation. Therefore, DDR1 represents a highly promising therapeutic target. Although no selective small-molecule inhibitors have reached clinical trials to date, many molecules have shown therapeutic effects in preclinical studies. For example, BK40143 has demonstrated significant promise in the therapy of neurodegenerative diseases. In this context, our perspective aims to provide an in-depth exploration of DDR1, encompassing its structure characteristics, biological functions, and disease relevance. Furthermore, we emphasize the importance of understanding the structure-activity relationship of DDR1 inhibitors and highlight the unique advantages of dual-target or multitarget inhibitors. We anticipate offering valuable insights into the development of more efficacious DDR1-targeted drugs.


Assuntos
Receptor com Domínio Discoidina 1 , Neoplasias , Humanos , Receptores Proteína Tirosina Quinases , Colágeno , Neoplasias/tratamento farmacológico , Inflamação
15.
Adv Mater ; 36(23): e2400537, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38336365

RESUMO

Ionic liquid electrolytes (ILEs) are promising to develop high-safety and high-energy-density lithium-metal batteries (LMBs). Unfortunately, ILEs normally face the challenge of sluggish Li+ transport due to increased ions' clustering caused by Coulombic interactions. Here a type of anion-reinforced solvating ILEs (ASILEs) is discovered, which reduce ions' clustering by enhancing the anion-cation coordination and promoting more anions to enter the internal solvation sheath of Li+ to address this concern. The designed ASILEs, incorporating chlorinated hydrocarbons and two anions, bis(fluorosulfonyl) imide (FSI-) and bis(trifluoromethanesulfonyl) imide (TFSI-), aim to enhance Li+ transport ability, stabilize the interface of the high-nickel cathode material (LiNi0.8Co0.1Mn0.1O2, NCM811), and retain fire-retardant properties. With these ASILEs, the Li/NCM811 cell exhibits high initial specific capacity (203 mAh g-1 at 0.1 C), outstanding capacity retention (81.6% over 500 cycles at 1.0 C), and excellent average Coulombic efficiency (99.9% over 500 cycles at 1.0 C). Furthermore, an Ah-level Li/NCM811 pouch cell achieves a notable energy density of 386 Wh kg-1, indicating the practical feasibility of this electrolyte. This research offers a practical solution and fundamental guidance for the rational design of advanced ILEs, enabling the development of high-safety and high-energy-density LMBs.

16.
Front Immunol ; 15: 1275064, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38370408

RESUMO

Introduction: Idiopathic pulmonary fibrosis (IPF) is characterized by progressive lung dysfunction due to excessive collagen production and tissue scarring. Despite recent advancements, the molecular mechanisms remain unclear. Methods: RNA sequencing identified 475 differentially expressed genes (DEGs) in the TGF-ß1-induced primary lung fibrosis model. Gene expression chips GSE101286 and GSE110147 from NCBI gene expression omnibus (GEO) database were analyzed using GEO2R, revealing 94 DEGs in IPF lung tissue samples. The gene ontology (GO) and pathway enrichment, Protein-protein interaction (PPI) network construction, and Maximal Clique Centrality (MCC) scoring were performed. Experimental validation included RT-qPCR, Immunohistochemistry (IHC), and Western Blot, with siRNA used for gene knockdown. A co-expression network was constructed by GeneMANIA. Results: GO enrichment highlighted significant enrichment of DEGs in TGF-ß cellular response, connective tissue development, extracellular matrix components, and signaling pathways such as the AGE-RAGE signaling pathway and ECM-receptor interaction. PPI network analysis identified hub genes, including FN1, COL1A1, POSTN, KIF11, and ECT2. CALD1 (Caldesmon 1), CDH2 (Cadherin 2), and POSTN (Periostin) were identified as dysregulated hub genes in both the RNA sequencing and GEO datasets. Validation experiments confirmed the upregulation of CALD1, CDH2, and POSTN in TGF-ß1-treated fibroblasts and IPF lung tissue samples. IHC experiments probed tissue-level expression patterns of these three molecules. Knockdown of CALD1, CDH2, and POSTN attenuated the expression of fibrotic markers (collagen I and α-SMA) in response to TGF-ß1 stimulation in primary fibroblasts. Co-expression analysis revealed interactions between hub genes and predicted genes involved in actin cytoskeleton regulation and cell-cell junction organization. Conclusions: CALD1, CDH2, and POSTN, identified as potential contributors to pulmonary fibrosis, present promising therapeutic targets for IPF patients.


Assuntos
Fibrose Pulmonar Idiopática , Fator de Crescimento Transformador beta1 , Humanos , Antígenos CD/metabolismo , Caderinas/genética , Caderinas/metabolismo , Proteínas de Ligação a Calmodulina/metabolismo , Moléculas de Adesão Celular/metabolismo , Colágeno/metabolismo , Fibroblastos/metabolismo , Expressão Gênica , Fibrose Pulmonar Idiopática/genética , Fibrose Pulmonar Idiopática/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
17.
CNS Neurosci Ther ; 30(2): e14577, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38421107

RESUMO

BACKGROUND: Glucocorticoids (GCs) are steroidal hormones produced by the adrenal cortex. A physiological-level GCs have a crucial function in maintaining many cognitive processes, like cognition, memory, and mood, however, both insufficient and excessive GCs impair these functions. Although this phenomenon could be explained by the U-shape of GC effects, the underlying mechanisms are still not clear. Therefore, understanding the underlying mechanisms of GCs may provide insight into the treatments for cognitive and mood-related disorders. METHODS: Consecutive administration of corticosterone (CORT, 10 mg/kg, i.g.) proceeded for 28 days to mimic excessive GCs condition. Adrenalectomy (ADX) surgery was performed to ablate endogenous GCs in mice. Microinjection of 1 µL of Ad-mTERT-GFP virus into mouse hippocampus dentate gyrus (DG) and behavioral alterations in mice were observed 4 weeks later. RESULTS: Different concentrations of GCs were shown to affect the cell growth and development of neural stem cells (NSCs) in a U-shaped manner. The physiological level of GCs (0.01 µM) promoted NSC proliferation in vitro, while the stress level of GCs (10 µM) inhibited it. The glucocorticoid synthesis blocker metyrapone (100 mg/kg, i.p.) and ADX surgery both decreased the quantity and morphological development of doublecortin (DCX)-positive immature cells in the DG. The physiological level of GCs activated mineralocorticoid receptor and then promoted the production of telomerase reverse transcriptase (TERT); in contrast, the stress level of GCs activated glucocorticoid receptor and then reduced the expression of TERT. Overexpression of TERT by AD-mTERT-GFP reversed both chronic stresses- and ADX-induced deficiency of TERT and the proliferation and development of NSCs, chronic stresses-associated depressive symptoms, and ADX-associated learning and memory impairment. CONCLUSION: The bidirectional regulation of TERT by different GCs concentrations is a key mechanism mediating the U-shape of GC effects in modulation of hippocampal NSCs and associated brain function. Replenishment of TERT could be a common treatment strategy for GC dysfunction-associated diseases.


Assuntos
Glucocorticoides , Células-Tronco Neurais , Camundongos , Animais , Glucocorticoides/farmacologia , Glucocorticoides/metabolismo , Hipocampo/metabolismo , Corticosterona/farmacologia , Células-Tronco Neurais/metabolismo , Transtornos da Memória/metabolismo
18.
Int J Hyperthermia ; 41(1): 2320416, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38413385

RESUMO

OBJECTIVE: The aim of this retrospective study was to investigate the short-term and long-term efficacy of high-intensity focused ultrasound (HIFU) therapy for abdominal wall endometriosis (AWE) and explore its potential influencing factors. MATERIALS AND METHODS: A total of 80 patients with AWE who underwent HIFU therapy were retrospectively analyzed. Follow-ups were also conducted to evaluate the changes in lesion size and pain relief. Multivariate logistic regression analysis was applied to investigate factors influencing HIFU therapy for AWE. RESULTS: Among the 80 patients with AWE who received HIFU therapy, the effective rates were 76.3%, 80.5%, and 90.5% after 3, 12 and 24 months of follow-up, respectively. Multivariate logistic regression analysis revealed that the AWE lesion diameter and sonication intensity had statistically significant effects on the 3-month and 12-month efficacy of HIFU therapy for AWE, while age, BMI, disease duration, average sonication power and grey-scale changes did not have statistically significant effects. Four patients with AWE experienced recurrence after HIFU therapy, for a three-year cumulative recurrence rate of 6.3%. Furthermore, ten patients required reintervention after treatment, for a five-year cumulative reintervention rate of 13.9%. CONCLUSIONS: This study further confirmed the safety and effectiveness of HIFU therapy for AWE. Factors such as AWE lesion diameter and sonication intensity have been identified as key influencers affecting the short-term and long-term efficacy of HIFU therapy for AWE. The first two years following HIFU therapy constitute crucial periods for observation, and judiciously extending follow-up intervals during this timeframe is advised.


Assuntos
Parede Abdominal , Endometriose , Tratamento por Ondas de Choque Extracorpóreas , Ablação por Ultrassom Focalizado de Alta Intensidade , Feminino , Humanos , Endometriose/diagnóstico por imagem , Endometriose/terapia , Estudos Retrospectivos , Ablação por Ultrassom Focalizado de Alta Intensidade/efeitos adversos , Resultado do Tratamento
19.
Chem Commun (Camb) ; 60(3): 348-351, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38078506

RESUMO

A facile one-step solvothermal method was developed to synthesize Ir-doped Co-based metal-organic framework (CoIr-MOF) nanoarrays as a bifunctional electrocatalyst for water-glucose co-electrolysis. It was demonstrated that in situ incorporation of a low-content of Ir cations could modulate the electronic structure of Co active centers and thus boost the electrocatalytic performance towards both the hydrogen evolution reaction and glucose-to-formate oxidation reaction.

20.
Respir Res ; 24(1): 296, 2023 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-38007420

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive scarring interstitial lung disease with an unknown cause. Some patients may experience acute exacerbations (AE), which result in severe lung damage visible on imaging or through examination of tissue samples, often leading to high mortality rates. However, the etiology and pathogenesis of AE-IPF remain unclear. AE-IPF patients exhibit diffuse lung damage, apoptosis of type II alveolar epithelial cells, and an excessive inflammatory response. Establishing a reliable animal model of AE is critical for investigating the pathogenesis. Recent studies have reported a variety of animal models for AE-IPF, each with its own advantages and disadvantages. These models are usually established in mice with bleomycin-induced pulmonary fibrosis, using viruses, bacteria, small peptides, or specific drugs. In this review, we present an overview of different AE models, hoping to provide a useful resource for exploring the mechanisms and targeted therapies for AE-IPF.


Assuntos
Fibrose Pulmonar Idiopática , Humanos , Animais , Camundongos , Fibrose Pulmonar Idiopática/diagnóstico , Pulmão , Modelos Animais , Progressão da Doença
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