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1.
J Steroid Biochem Mol Biol ; 243: 106577, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38971336

RESUMO

An UPLC-APCI-MS/MS method was developed for the simultaneous determination of cholesterol, 7-dehydrocholesterol (7DHC) and eight oxysterols including 27-hydroxycholesterol (27OHC), 7α-hydroxycholesterol (7αOHC), 7ß-hydroxycholesterol (7ßOHC), 24S-hydroxycholesterol (24SOHC), 25-hydroxycholesterol (25OHC), 7α,24S-dihydroxycholesterol (7α,24SdiOHC), 7α,25-dihydroxycholesterol (7α,25diOHC), and 7α,27-dihydroxycholesterol (7α,27diOHC). It has been used for quantitative analysis of cholesterol, 7DHC and eight oxysterols in hepatocellular carcinoma (HCC) cells, plasma and tumor tissue samples. And the above compounds were extracted from the biological matrix (plasma and tissue) using liquid-liquid extraction with hexane/isopropanol after saponification to cleave the steroids from their esterified forms without further derivatization. Then cholesterol, 7DHC and oxysterols were separated on a reversed phase column (Agilent Zorbax Eclipse plus, C18) within 8 min using a gradient elution with 0.1 % formic acid in H2O and methanol and detected by an APCI triple quadrupole mass spectrometer. The lower limit of quantification (LLOQ) of the cholesterol, 7DHC and oxysterols ranged from 3.9 ng/mL to 31.25 ng/mL, and the recoveries ranged from 83.0 % to 113.9 %. Cholesterol, 7DHC and several oxysterols including 27OHC, 7αOHC and 7ßOHC were successfully quantified in HCC cells, plasma, tissues and urine of HCC mice. Results showed that 27OHC was at high levels in three kind of HCC cells and tumor tissues as well as plasma samples from both HepG2 and Huh7 bearing mice model,and the high levels of 27OHC in tumors were associated with HCC development. Moreover, the levels of cholesterol in HCC cells and tumor issues varied in different HCC cells and mice model. Oxysterols profiling in biological samples might provide complementary information in cancer diagnosis.

2.
J Phys Chem A ; 128(28): 5459-5472, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-38973649

RESUMO

In this study, we employ density functional theory along with the artificial bee colony algorithm for cluster global optimization to explore the low-lying structures of TeBnq (n = 3-16, q = 0, -1). The primary focus is on reporting the structural properties of these clusters. The results reveal a consistent doping pattern of the tellurium atom onto the in-plane edges of planar or quasi-planar boron clusters in the most energetically stable isomers. Additionally, we simulate the photoelectron spectra of the cluster anions. Through relative stability analysis, we identify three clusters with magic numbers -TeB7-, TeB10, and TeB12. The aromaticity of these clusters is elucidated using adaptive natural density partitioning (AdNDP) and magnetic properties analysis. Notably, TeB7- exhibits a perfect σ-π doubly aromatic structure, while TeB12 demonstrates strong island aromaticity. These findings significantly contribute to our understanding of the structural and electronic properties of these clusters.

3.
Cell Death Discov ; 10(1): 323, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39009585

RESUMO

Adipose tissue, aside from adipocytes, comprises various abundant immune cells. The accumulation of low-grade chronic inflammation in adipose tissue serves as a primary cause and hallmark of insulin resistance. In this study, we investigate the physiological roles of FADD in adipose tissue inflammation, adipogenesis, and adipocyte survival. High levels of Fadd mRNA were observed in mitochondrial-rich organs, particularly brown adipose tissue. To explore its metabolic functions, we generated global Fadd knockout mice, resulting in embryonic lethality, while heterozygous knockout (Fadd+/-) mice did not show any significant changes in body weight or composition. However, Fadd+/- mice exhibited reduced respiratory exchange ratio (RER) and serum cholesterol levels, along with heightened global and adipose inflammatory responses. Furthermore, AT masses and expression levels of adipogenic and lipogenic genes were decreased in Fadd+/- mice. In cellular studies, Fadd inhibition disrupted adipogenic differentiation and suppressed the expression of adipogenic and lipogenic genes in cultured adipocytes. Additionally, Fadd overexpression caused adipocyte death in vitro with decreased RIPK1 and RIPK3 expression, while Fadd inhibition downregulated RIPK3 in iWAT in vivo. These findings collectively underscore the indispensable role of FADD in adipose inflammation, adipogenesis, and adipocyte survival.

4.
Adv Mater ; : e2405852, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39021291

RESUMO

The utilization of seawater for hydrogen production via water splitting is increasingly recognized as a promising avenue for the future. The key dilemma for seawater electrolysis is the incompatibility of superior hydrogen- and oxygen-evolving activities at ampere-scale current densities for both cathodic and anodic catalysts, thus leading to large electric power consumption of overall seawater splitting. Here, in situ construction of Fe4N/Co3N/MoO2 heterostructure arrays anchoring on metallic nickel nitride surface with multilevel collaborative catalytic interfaces and abundant multifunctional metal sites is reported, which serves as a robust bifunctional catalyst for alkaline freshwater/seawater splitting at ampere-level current density. Operando Raman and X-ray photoelectron spectroscopic studies combined with density functional theory calculations corroborate that Mo and Co/Fe sites situated on the Fe4N/Co3N/MoO2 multilevel interfaces optimize the reaction pathway and coordination environment to enhance water adsorption/dissociation, hydrogen adsorption, and oxygen-containing intermediate adsorption, thus cooperatively expediting hydrogen/oxygen evolution reactions in base. Inspiringly, this electrocatalyst can substantially ameliorate overall freshwater/seawater splitting at 1000 mA cm-2 with low cell voltages of 1.65/1.69 V, along with superb long-term stability at 500-1500 mA cm-2 for over 200 h, outperforming nearly all the ever-reported non-noble electrocatalysts for freshwater/seawater electrolysis. This work offers a viable approach to design high-performance bifunctional catalysts for seawater splitting.

5.
Adv Healthc Mater ; : e2401586, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39023386

RESUMO

Synergistic therapy has become the major therapeutic method for malignant tumors in clinical. Photodynamic therapy (PDT) and radiotherapy (RT) always combine together because of their identical anti-tumor mechanisms, that is reactive oxygen species are generated by the use of radiosensitizers after irradiation by X-ray to efficiently kill cancer cells, PDT also follows similar mechanism. Full exposure of energy-absorbing species in nanomaterials to X-ray or near-infrared light irradiation makes the energy interchange between nanomaterials and surrounding H2O or dissolved oxygen easier, however, it remains challenging. Herein, an ultrathin two-dimensional (2D) nanosheet (NS) is developed, Bi2O2CO3, doped with lanthanide ions to give out upconversion luminescence, where the high Z elements Bi, Yb, and Er promote the radio-sensitizing effect. To the surprise, lanthanide activator ions gave out completely different luminescence properties compared with traditional upconversion nanoparticles. Less dopant of Er ions in nanosheets lattice resulted in brighter red emission, which provides more efficient PDT. Under RT/PDT combined treatment, NS shows a good tumor growth-inhibiting effect. In addition, synergistic therapy requires lower radiation dose than conventional radiotherapy and lower light power than single photodynamic therapy, thus greatly reducing radiation damage caused by RT and thermal damage caused by PDT.

6.
Adv Sci (Weinh) ; : e2310037, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38953362

RESUMO

Programmed death-ligand 1 (PD-L1) is overexpressed in multiple cancers and critical for their immune escape. It has previously shown that the nuclear coactivator SRC-1 promoted colorectal cancer (CRC) progression by enhancing CRC cell viability, yet its role in CRC immune escape is unclear. Here, we demonstrate that SRC-1 is positively correlated with PD-L1 in human CRC specimens. SRC-1 deficiency significantly inhibits PD-L1 expression in CRC cells and retards murine CRC growth in subcutaneous grafts by enhancing CRC immune escape via increasing tumor infiltration of CD8+ T cells. Genetic ablation of SRC-1 in mice also decreases PD-L1 expression in AOM/DSS-induced murine CRC. These results suggest that tumor-derived SRC-1 promotes CRC immune escape by enhancing PD-L1 expression. Mechanistically, SRC-1 activated JAK-STAT signaling by inhibiting SOCS1 expression and coactivated STAT3 and IRF1 to enhance PD-L1 transcription as well as stabilized PD-L1 protein by inhibiting proteasome-dependent degradation mediated by speckle type POZ protein (SPOP). Pharmacological inhibition of SRC-1 improved the antitumor effect of PD-L1 antibody in both subcutaneous graft and AOM/DSS-induced murine CRC models. Taken together, these findings highlight a crucial role of SRC-1 in regulating PD-L1 expression and targeting SRC-1 in combination with PD-L1 antibody immunotherapy may be an attractive strategy for CRC treatment.

7.
J Chromatogr A ; 1730: 465130, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38955130

RESUMO

This study describes the preparation of a cylindrical polymer foam column termed Chitosan/ß-Cyclodextrin/MIL-68(Al) (CS/ß-CD/MIL-68(Al)). An ice template-freeze drying technique was employed to prepare the CS/ß-CD/MIL-68(Al) foam column by embedding MIL-68(Al) in a polymer matrix comprising cross-linked chitosan (CS) and ß-cyclodextrin (ß-CD). The cylindrical CS/ß-CD/MIL-68(Al) foam was subsequently inserted into a syringe to develop a solid phase extraction (SPE) device. Without the requirement for an external force, the sample solution passed easily through the SPE column thanks to the porous structure of the CS/ß-CD/MIL-68(Al) foam column. Moreover, the CS/ß-CD/MIL-68(Al) foam column was thought to be a superior absorbent for SPE since it included the adsorptive benefits of CS, ß-CD, and MIL-68(Al). The SPE was utilized in conjunction with high-performance liquid chromatography to analyze six sulfonamides found in milk, urine, and water. With matrix effects ranging from 80.49 % to 104.9 % with RSD values of 0.4-14.0 %, the method showed high recoveries ranging from 80.6 to 107.4 % for water samples, 93.4-105.2 % for urine, and 87.4-100.9 % for milk. It also demonstrated good linearity in the range of 10-258 ng·mL-1 with the limits of detection ranging from 1.88 to 2.58 ng·mL-1. The cylindrical CS/ß-CD/MIL-68(Al) foam column prepared in this work offered several advantages, including its simple fabrication, excellent water stability, absence of pollutants, biodegradability, and reusability. It is particularly well-suited for SPE. Furthermore, the developed SPE method, employing CS/ß-CD/MIL-68(Al) foam column, is straightforward and precise, and its benefits, including affordability, ease of preparation, lack of specialized equipment, and solvent economy, underline its broad applicability for the pretreatment of aqueous samples.

8.
Pediatr Res ; 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38951655

RESUMO

BACKGROUND: Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease (CCHD) with multifactorial etiology. We aimed to investigate the metabolic profiles of CCHD and their independent contributions to TOF. METHODS: A cohort comprising 42 individuals with TOF and atrial septal defect (ASD) was enrolled. Targeted ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) was employed to systematically analyze metabolite levels and identify TOF-associated metabolic profiles. RESULTS: Of 370 identified metabolites in tissue and 284 in plasma, over one-third of metabolites showed an association with microbiome. Differential metabolic pathways including amino acids biosynthesis, ABC (ATP-binding cassette) transporters, carbon metabolism, and fatty acid biosynthesis, shed light on TOF biological phenotypes. Additionally, ROC curves identified potential biomarkers, such as erythronic acid with an AUC of 0.868 in plasma, and 3-ß-hydroxy-bisnor-5-cholenic acid, isocitric acid, glutaric acid, ortho-Hydroxyphenylacetic acid, picolinic acid with AUC close to 1 in tissue, whereas the discriminative performance of those substances significantly improved when combined with clinical phenotypes. CONCLUSIONS: Distinct metabolic profiles exhibited robust discriminatory capabilities, effectively distinguishing TOF from ASD patients. These metabolites may serve as biomarkers or key molecular players in the intricate metabolic pathways involved in CCHD development. IMPACT: Distinct metabolic profiles exhibited robust discriminatory capabilities, effectively distinguishing Tetralogy of Fallot from atrial septal defect patients. Similar profiling but inconsistent differential pathways between plasma and tissue. More than one-third metabolites in plasma and tissue are associated with the microbiome. The discovery of biomarkers is instrumental in facilitating early detection and diagnosis of Tetralogy of Fallot. Disturbed metabolism offers insights into interpretation of pathogenesis of Tetralogy of Fallot.

9.
ACS Sens ; 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38982583

RESUMO

Mutation accumulation in RNAs results in closely located single-nucleotide mutations (SNMs), which is highly associated with the drug resistance of pathogens. Imaging of SNMs in single cells has significance for understanding the heterogeneity of RNAs that are related to drug resistance, but the direct "see" closely located SNMs remains challenging. Herein, we designed an encoded ligation-mediated in situ polymerase chain reaction method (termed enPCR), which enabled the visualization of multiple closely located SNMs in bacterial RNAs. Unlike conventional ligation-based probes that can only discriminate a single SNM, this method can simultaneously image different SNMs at closely located sites with single-cell resolution using modular anchoring probes and encoded PCR primers. We tested the capacity of the method to detect closely located SNMs related to quinolone resistance in the gyrA gene of Salmonella enterica (S. enterica), and found that the simultaneous detection of the closely located SNMs can more precisely indicate the resistance of the S. enterica to quinolone compared to the detection of one SNM. The multiplexing imaging assay for SNMs can serve to reveal the relationship between complex cellular genotypes and phenotypes.

10.
J Immunol ; 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38984862

RESUMO

Teleost IgM+ B cells can phagocytose, like mammalian B1 cells, and secrete Ag-specific IgM, like mammalian B2 cells. Therefore, teleost IgM+ B cells may have the functions of both mammalian B1 and B2 cells. To support this view, we initially found that grass carp (Ctenopharyngodon idella) IgM+ plasma cells (PCs) exhibit robust phagocytic ability, akin to IgM+ naive B cells. Subsequently, we sorted grass carp IgM+ PCs into two subpopulations: nonphagocytic (Pha-IgM+ PCs) and phagocytic IgM+ PCs (Pha+IgM+ PCs), both of which demonstrated the capacity to secrete natural IgM with LPS and peptidoglycan binding capacity. Remarkably, following immunization of grass carp with an Ag, we observed that both Pha-IgM+ PCs and Pha+IgM+ PCs could secrete Ag-specific IgM. Furthermore, in vitro concatenated phagocytosis experiments in which Pha-IgM+ PCs from an initial phagocytosis experiment were sorted and exposed again to beads confirmed that these cells also have phagocytic capabilities, thereby suggesting that all teleost IgM+ B cells have phagocytic potential. Additionally, we found that grass carp IgM+ PCs display classical phenotypic features of macrophages, providing support for the hypothesis that vertebrate B cells evolved from ancient phagocytes. These findings together reveal that teleost B cells are a primitive B cell type with functions reminiscent of both mammalian B1 and B2 cells, providing insights into the origin and evolution of B cells in vertebrates.

11.
Trends Microbiol ; 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38987051

RESUMO

Despite global yield benefits from the use of nitrification inhibitors (NIs), the uncertainties and limitations surrounding NIs warrant more attention. Understanding the impacts of NIs on the health of organisms, people, and ecosystems is also crucial. Here we present a global budget, current challenges, and future research priorities of NIs.

13.
Acta Pharmacol Sin ; 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38992119

RESUMO

The escalating obesity epidemic and aging population have propelled metabolic dysfunction-associated steatohepatitis (MASH) to the forefront of public health concerns. The activation of FXR shows promise to combat MASH and its detrimental consequences. However, the specific alterations within the MASH-related transcriptional network remain elusive, hindering the development of more precise and effective therapeutic strategies. Through a comprehensive analysis of liver RNA-seq data from human and mouse MASH samples, we identified central perturbations within the MASH-associated transcriptional network, including disrupted cellular metabolism and mitochondrial function, decreased tissue repair capability, and increased inflammation and fibrosis. By employing integrated transcriptome profiling of diverse FXR agonists-treated mice, FXR liver-specific knockout mice, and open-source human datasets, we determined that hepatic FXR activation effectively ameliorated MASH by reversing the dysregulated metabolic and inflammatory networks implicated in MASH pathogenesis. This mitigation encompassed resolving fibrosis and reducing immune infiltration. By understanding the core regulatory network of FXR, which is directly correlated with disease severity and treatment response, we identified approximately one-third of the patients who could potentially benefit from FXR agonist therapy. A similar analysis involving intestinal RNA-seq data from FXR agonists-treated mice and FXR intestine-specific knockout mice revealed that intestinal FXR activation attenuates intestinal inflammation, and has promise in attenuating hepatic inflammation and fibrosis. Collectively, our study uncovers the intricate pathophysiological features of MASH at a transcriptional level and highlights the complex interplay between FXR activation and both MASH progression and regression. These findings contribute to precise drug development, utilization, and efficacy evaluation, ultimately aiming to improve patient outcomes.

14.
Front Public Health ; 12: 1413986, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38989128

RESUMO

Background: Burns are a prevalent form of unintentional injury and a significant public health concern in developing countries. We aimed to investigate the epidemiological and clinical characteristics of adult burn patients at a major center in Eastern China. Methods: This 6-year retrospective study analyzed patients with varying degrees of burns between January 2017 and December 2022 at the Suzhou Burns and Trauma Center. The study extracted demographic, clinical, and epidemiological data from electronic medical records for analysis. Results: The study included 3,258 adult patients, of which 64.3% were male. The largest age group affected 30-59-year-old adults (63.04%). Scalds were the leading cause of burns (1,346, 41.31%), followed by flames (1,271, 39.01%). The majority of burn hospitalizations were those with moderate burns (1791, 54.97%). The morbidity rate was low at 0.68%, while mortality was strongly associated with age, etiology, and total body surface area. Patients with certain types of burns, such as explosions, hot crush injuries, and electric burns had more operations, longer lengths of hospital stay, and higher costs compared to those with scalds and flame injuries. Conclusion: Different prevention strategies should be formulated according to different etiologies, ages, and genders.


Assuntos
Unidades de Queimados , Queimaduras , Humanos , Masculino , Estudos Retrospectivos , Queimaduras/epidemiologia , China/epidemiologia , Adulto , Feminino , Pessoa de Meia-Idade , Unidades de Queimados/estatística & dados numéricos , Idoso , Adulto Jovem , Hospitalização/estatística & dados numéricos , Adolescente , Tempo de Internação/estatística & dados numéricos
15.
Front Genet ; 15: 1293668, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38993479

RESUMO

Introduction: Observational investigations have examined the impact of glucosamine use on the risk of cancer and non-neoplastic diseases. However, the findings from these studies face limitations arising from confounding variables, reverse causation, and conflicting reports. Consequently, the establishment of a causal relationship between habitual glucosamine consumption and the risk of cancer and non-neoplastic diseases necessitates further investigation. Methods: For Mendelian randomization (MR) investigation, we opted to employ single-nucleotide polymorphisms (SNPs) as instruments that exhibit robust associations with habitual glucosamine consumption. We obtained the corresponding effect estimates of these SNPs on the risk of cancer and non-neoplastic diseases by extracting summary data for genetic instruments linked to 49 varied cancer types amounting to 378,284 cases and 533,969 controls, as well as 20 non-neoplastic diseases encompassing 292,270 cases and 842,829 controls. Apart from the primary analysis utilizing inverse-variance weighted MR, we conducted two supplementary approaches to account for potential pleiotropy (MR-Egger and weighted median) and assessed their respective MR estimates. Furthermore, the results of the leave-one-out analysis revealed that there were no outlying instruments. Results: Our results suggest divergence from accepted biological understanding, suggesting that genetically predicted glucosamine utilization may be linked to an increased vulnerability to specific illnesses, as evidenced by increased odds ratios and confidence intervals (95% CI) for diseases, such as malignant neoplasm of the eye and adnexa (2.47 [1.34-4.55]), benign neoplasm of the liver/bile ducts (2.12 [1.32-3.43]), benign neoplasm of the larynx (2.01 [1.36-2.96]), melanoma (1.74 [1.17-2.59]), follicular lymphoma (1.50 [1.06-2.11]), autoimmune thyroiditis (2.47 [1.49-4.08]), and autoimmune hyperthyroidism (1.93 [1.17-3.18]). In contrast to prior observational research, our genetic investigations demonstrate a positive correlation between habitual glucosamine consumption and an elevated risk of sigmoid colon cancer, lung adenocarcinoma, and benign neoplasm of the thyroid gland. Conclusion: Casting doubt on the purported purely beneficial association between glucosamine ingestion and prevention of neoplastic and non-neoplastic diseases, habitual glucosamine ingestion exhibits dichotomous effects on disease outcomes. Endorsing the habitual consumption of glucosamine as a preventative measure against neoplastic and non-neoplastic diseases cannot be supported.

16.
J Am Chem Soc ; 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39001844

RESUMO

The utility of antibody therapeutics is hampered by potential cross-reactivity with healthy tissue. Over the past decade, significant advances have been made in the design of activatable antibodies, which increase, or create altogether, the therapeutic window of a parent antibody. Of these, antibody prodrugs (pro-antibodies) are masked antibodies that have advanced the most for therapeutic use. They are designed to reveal the active, parent antibody only when encountering proteases upregulated in the microenvironment of the targeted disease tissue, thereby minimizing off-target activity. However, current pro-antibody designs are relegated to fusion proteins that append masking groups restricted to the use of only canonical amino acids, offering excellent control of the site of introduction, but with no authority over where the masking group is installed other than the N-terminus of the antibody. Here, we present a palladium-based bioconjugation approach for the site-specific introduction of a masked tyrosine mimic in the complementary determining region of the FDA approved antibody therapeutic ipilimumab used as a model system. The approach enables the introduction of a protease cleavable group tethered to noncanonical polymers (polyethylene glycol (PEG)) resulting in 47-fold weaker binding to cells expressing CTLA-4, the target antigen of ipilimumab. Upon exposure to tumor-associated proteases, the masking group is cleaved, unveiling a tyrosine-mimic (dubbed hydroxyphenyl cysteine (HPC)) that restores (>90% restoration) binding affinity to its target antigen.

17.
Int J Mol Sci ; 25(13)2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-39000602

RESUMO

The application of intracerebroventricular injection of streptozotocin (ICV-STZ) is considered a useful animal model to mimic the onset and progression of sporadic Alzheimer's disease (sAD). In rodents, on day 7 of the experiment, the animals exhibit depression-like behaviors. Indoleamine 2,3-dioxygenase (IDO), a rate-limiting enzyme catalyzing the conversion of tryptophan (Trp) to kynurenine (Kyn), is closely related to depression and AD. The present study aimed to investigate the pathophysiological mechanisms of preliminary depression-like behaviors in ICV-STZ rats in two distinct cerebral regions of the medial prefrontal cortex, the prelimbic cortex (PrL) and infralimbic cortex (IL), both presumably involved in AD progression in this model, with a focus on IDO-related Kyn pathways. The results showed an increased Kyn/Trp ratio in both the PrL and IL of ICV-STZ rats, but, intriguingly, abnormalities in downstream metabolic pathways were different, being associated with distinct biological effects. In the PrL, the neuroprotective branch of the Kyn pathway was attenuated, as evidenced by a decrease in the kynurenic acid (KA) level and Kyn aminotransferase II (KAT II) expression, accompanied by astrocyte alterations, such as the decrease in glial fibrillary acidic protein (GFAP)-positive cells and increase in morphological damage. In the IL, the neurotoxicogenic branch of the Kyn pathway was enhanced, as evidenced by an increase in the 3-hydroxy-kynurenine (3-HK) level and kynurenine 3-monooxygenase (KMO) expression paralleled by the overactivation of microglia, reflected by an increase in ionized calcium-binding adaptor molecule 1 (Iba1)-positive cells and cytokines with morphological alterations. Synaptic plasticity was attenuated in both subregions. Additionally, microinjection of the selective IDO inhibitor 1-Methyl-DL-tryptophan (1-MT) in the PrL or IL alleviated depression-like behaviors by reversing these different abnormalities in the PrL and IL. These results suggest that the antidepressant-like effects linked to Trp metabolism changes induced by 1-MT in the PrL and IL occur through different pathways, specifically by enhancing the neuroprotective branch in the PrL and attenuating the neurotoxicogenic branch in the IL, involving distinct glial cells.


Assuntos
Antidepressivos , Depressão , Indolamina-Pirrol 2,3,-Dioxigenase , Cinurenina , Estreptozocina , Triptofano , Animais , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Estreptozocina/toxicidade , Ratos , Masculino , Cinurenina/metabolismo , Antidepressivos/farmacologia , Antidepressivos/administração & dosagem , Triptofano/metabolismo , Triptofano/farmacologia , Depressão/tratamento farmacológico , Depressão/metabolismo , Depressão/induzido quimicamente , Injeções Intraventriculares , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/efeitos dos fármacos , Modelos Animais de Doenças , Ratos Sprague-Dawley
18.
Small ; : e2403082, 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39004856

RESUMO

Mechanical metamaterials with multi-level dynamic crushing effects (MM-MLs) are designed in this study through coordinate transformation and mirror arrays. The mechanical effects of the diameter and length ratio of the struts and connecting rods, the Euler angles, and the cell numbers on the mechanical properties are investigated separately. MM-ML can exhibit significant two-level platform stress, and the local cells in the first platform stress stage undergo rotational motion, while the second platform stress stage mainly involves collapse compression and bending. Although increasing the length of the connecting rods can increase the range of Poisson's ratio, it will reduce the level of platform stress and energy absorption. Increasing the Euler angle will reduce the strain interval of the first platform stress and can improve the energy absorption capacity. In addition, increasing the cell number while maintaining a constant relative density can effectively enhance energy absorption. MM-ML has significant parameter controllability, can achieve different platform stress regions, different ranges of Poisson's ratios, and energy absorption requirements according to the application scenario, and can demonstrate functional diversity compared to existing research. The design scheme can provide ideas for adaptive crushing protection requirements.

19.
Animals (Basel) ; 14(13)2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38998045

RESUMO

The aim of this study was to explore alterations in plasma metabolites among mares afflicted with endometritis. Mares were divided into two groups, namely, the equine endometritis group (n = 8) and the healthy control group (n = 8), which included four pregnant and four non-pregnant mares, using a combination of clinical assessment and laboratory confirmation. Plasma samples from both groups of mares were analyzed through untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) metabolomics. A total of 28 differentially abundant metabolites were identified by screening and identifying differentially abundant metabolites and analyzing the pathway enrichment of differentially. Ten metabolites were identified as potential biomarkers for the diagnosis of endometritis in mares. Among them, seven exhibited a decrease in the endometritis groups, including hexadecanedioic acid, oleoyl ethanolamide (OEA), [fahydroxy(18:0)]12_13-dihydroxy-9z-octa (12,13-diHOME), deoxycholic acid 3-glucuronide (DCA-3G), 2-oxindole, and (+/-)9-HPODE, and 13(S)-HOTRE. On the other hand, three metabolites, adenosine 5'-monophosphate (AMP), 5-hydroxy-dl-tryptophan (5-HTP), and l-formylkynurenine, demonstrated an increase. These substances primarily participate in the metabolism of tryptophan and linolenic acid, as well as fat and energy. In conclusion, metabolomics revealed differentially abundant metabolite changes in patients with mare endometritis. These specific metabolites can be used as potential biomarkers for the non-invasive diagnosis of mare endometritis.

20.
Plants (Basel) ; 13(13)2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38999678

RESUMO

Fruit softening is a prominent attribute governing both longevity on shelves and commercial worth. Polygalacturonase (PG) plays a major role in strawberry fruit softening. However, the PG gene family in strawberry has not been comprehensively analyzed. In this study, 75 FaPG genes were identified in the octoploid strawberry genome, which were classified into three groups according to phylogenetic analysis. Subcellular localization prediction indicated that FaPGs are mostly localized to the plasma membrane, cytoplasm, and chloroplasts. Moreover, the expression of FaPGs during strawberry development and ripening of 'Benihoppe' and its softer mutant was estimated. The results showed that among all 75 FaPGs, most genes exhibited low expression across developmental stages, while two group c members (FxaC_21g15770 and FxaC_20g05360) and one group b member, FxaC_19g05040, displayed relatively higher and gradual increases in their expression trends during strawberry ripening and softening. FxaC_21g15770 was selected for subsequent silencing to validate its role in strawberry softening due to the fact that it exhibited the highest and most changed expression level across different developmental stages in 'Benihoppe' and its mutant. Silencing FxaC_21g15770 could significantly improve strawberry fruit firmness without affecting fruit color, soluble solids, cellulose, and hemicellulose. Conversely, silencing FxaC_21g15770 could significantly suppress the expression of other genes related to pectin degradation such as FaPG-like, FaPL, FaPME, FaCX, FaCel, FaGlu, FaXET, and FaEG. These findings provide basic information on the FaPG gene family for further functional research and indicate that FxaC_21g15770 plays a vital role in strawberry fruit softening.

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