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1.
J Food Sci ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38955774

RESUMO

Soybean protein isolate (SPI) is a highly functional protein source used in various food applications, such as emulsion, gelatin, and food packaging. However, its commercial application may be limited due to its poor mechanical properties, barrier properties, and high water sensitivity. Studies have shown that modifying SPI through glycosylation can enhance its functional properties and biological activities, resulting in better application performance. This paper reviews the recent studies on glycosylation modification of SPI, including its quantification method, structural improvements, and enhancement of its functional properties, such as solubility, gelation, emulsifying, and foaming. The review also discusses how glycosylation affects the bioactivity of SPI, such as its antioxidant and antibacterial activity. This review aims to provide a reference for further research on glycosylation modification and lay a foundation for applying SPI in various fields.

3.
Clin Genitourin Cancer ; 22(5): 102114, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38959838

RESUMO

BACKGROUND: To evaluate the overall survival (OS) and construct a nomogram to predict the OS of patients with penile squamous cell carcinoma (PSCC). METHODS: This retrospective study analyzed data of patients with PSCC from the First Affiliated Hospital of Soochow University between 2012 and 2022. R software was used to explore factors influencing OS in PSCC. Kaplan-Meier method and log-rank test were employed for OS estimation. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify these factors. A nomogram was created to identify the independent prognostic factors. The model was evaluated by concordance index, receiver operating characteristic (ROC) curves, and calibration plots. RESULTS: A total of 159 patients with T1/T2 PSCC were included in the analysis. Patients with T2/N2 stage, older age, larger tumor size, high preoperative systemic immune-inflammation index (SII), and poor preoperative nutrition had a higher incidence of poor OS. Age, T/N stage, tumor size, and SII were identified as independent prognostic indicators. A prognostic nomogram was formulated, and its predictive accuracy for estimating OS in PSCC patients was validated through ROC curves and calibration plots. CONCLUSION: The nomograms, based on age, T/N stage, tumor size, and high preoperative SII, provide a valuable tool for predicting 1-, 2-, and 3-year OS in patients with T1/T2 PSCC without distant metastases.

4.
Artigo em Inglês | MEDLINE | ID: mdl-38961002

RESUMO

Pulmonary fibrosis is a debilitating lung disease marked by excessive fibrotic tissue accumulation, which significantly impairs respiratory function. Given the limitations of current therapies, there is an increasing interest in exploring traditional herbal formulations like Jie Geng Tang (JGT) for treatment. This study examines the potential of JGT and its bioactive component, quercetin, in reversing bleomycin (BLM)-induced pulmonary fibrosis in mice. We employed a BLM-induced MLE-12 cell damage model for in vitro studies and a bleomycin-induced fibrosis model in C57BL/6 mice for in vivo experiments. In vitro assessments showed that JGT significantly enhanced cell viability and reduced apoptosis in MLE-12 cells treated with BLM. These findings underscore JGT's potential for cytoprotection against fibrotic agents. In vivo, JGT was effective in modulating the expression of E-cadherin and vimentin, key markers of the epithelial-mesenchymal transition (EMT) pathway, indicating its role in mitigating EMT-associated fibrotic changes in lung tissue. Quercetin, identified through network pharmacology analysis as a potential key bioactive component of JGT, was highlighted for its role in the regulatory mechanisms underlying fibrosis progression, particularly through the modulation of the IL-17 pathway and Il6 expression. By targeting inflammatory pathways and key processes like EMT, JGT and quercetin offer a potent alternative to conventional therapies, meriting further clinical exploration to harness their full therapeutic potential in fibrotic diseases.

5.
Plant Cell Environ ; 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38963088

RESUMO

The regulation of legume-rhizobia symbiosis by microorganisms has obtained considerable interest in recent research, particularly in the common rhizobacteria Bacillus. However, few studies have provided detailed explanations regarding the regulatory mechanisms involved. Here, we investigated the effects of Bacillus (Bac.B) on Bradyrhizobium-soybean (Glycine max) symbiosis and elucidated the underlying ecological mechanisms. We found that two Bradyrhizobium strains (i.e. Bra.Q2 and Bra.D) isolated from nodules significantly promoted nitrogen (N) efficiency of soybean via facilitating nodule formation, thereby enhanced plant growth and yield. However, the intrusion of Bac.B caused a reverse shift in the synergistic efficiency of N2 fixation in the soybean-Bradyrhizobium symbiosis. Biofilm formation and naringenin may be importantin suppression of Bra.Q2 growth regulated by Bac.B. In addition, transcriptome and microbiome analyses revealed that Bra.Q2 and Bac.B might interact to regulateN transport and assimilation, thus influence the bacterial composition related to plant N nutrition in nodules. Also, the metabolisms of secondary metabolites and hormones associated with plant-microbe interaction and growth regulation were modulated by Bra.Q2 and Bac.B coinoculation. Collectively, we demonstrate that Bacillus negatively affects Bradyrhizobium-soybean symbiosis and modulate microbial interactions in the nodule. Our findings highlight a novel Bacillus-based regulation to improve N efficiency and sustainable agricultural development.

6.
BMC Med Imaging ; 24(1): 165, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956579

RESUMO

BACKGROUND: Pneumoconiosis has a significant impact on the quality of patient survival due to its difficult staging diagnosis and poor prognosis. This study aimed to develop a computer-aided diagnostic system for the screening and staging of pneumoconiosis based on a multi-stage joint deep learning approach using X-ray chest radiographs of pneumoconiosis patients. METHODS: In this study, a total of 498 medical chest radiographs were obtained from the Department of Radiology of West China Fourth Hospital. The dataset was randomly divided into a training set and a test set at a ratio of 4:1. Following histogram equalization for image enhancement, the images were segmented using the U-Net model, and staging was predicted using a convolutional neural network classification model. We first used Efficient-Net for multi-classification staging diagnosis, but the results showed that stage I/II of pneumoconiosis was difficult to diagnose. Therefore, based on clinical practice we continued to improve the model by using the Res-Net 34 Multi-stage joint method. RESULTS: Of the 498 cases collected, the classification model using the Efficient-Net achieved an accuracy of 83% with a Quadratic Weighted Kappa (QWK) score of 0.889. The classification model using the multi-stage joint approach of Res-Net 34 achieved an accuracy of 89% with an area under the curve (AUC) of 0.98 and a high QWK score of 0.94. CONCLUSIONS: In this study, the diagnostic accuracy of pneumoconiosis staging was significantly improved by an innovative combined multi-stage approach, which provided a reference for clinical application and pneumoconiosis screening.


Assuntos
Aprendizado Profundo , Pneumoconiose , Humanos , Pneumoconiose/diagnóstico por imagem , Pneumoconiose/patologia , Masculino , Pessoa de Meia-Idade , Feminino , Radiografia Torácica/métodos , Idoso , Adulto , Redes Neurais de Computação , China , Diagnóstico por Computador/métodos , Interpretação de Imagem Radiográfica Assistida por Computador/métodos
7.
Allergol Immunopathol (Madr) ; 52(4): 15-20, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38970260

RESUMO

BACKGROUND: Pulmonary fibrosis (PF) is a chronic, progressive, and irreversible heterogeneous disease of lung interstitial tissue. To combat progression of PF, new drugs are required to be developed. Rhizoma coptidis (COP), one of the main alkaloids of Coptis chinensis, is a traditional herbal medicine used to treat various inflammatory diseases. OBJECTIVE: To investigate the possible effects of Coptisine (Cop) on the growth, inflammation, as well as FMT of TNF-ß1-induced HFL1 cells and uncover the mechanism. MATERIAL AND METHODS: Human fetal lung fibroblast 1 (HFL1) was induced using 6ng/mL TGF-ß1 as a model of pulmonary fibrosis. CCK-8, Brdu, and transwell assays indicated the effects on cell growth as well as motility. qPCR and the corresponding kits indicted the effects on cell inflammation. Immunoblot showed the effects on FMT and further confirmed the mechanism. RESULTS: Coptisine inhibits excessive growth as well as motility of TNF-ß1-induced HFL1 cells. It further inhibits inflammation and ROS levels in TNF-ß1-induced HFL1 cells. Coptisine inhibits the FMT process of TNF-ß1-induced HFL1 cells. Mechanically, coptisine promotes the Nrf2/HO-1 pathway. CONCLUSION: Coptisine can inhibit the excessive growth, inflammation as well as FMT of lung fibroblasts into myofibroblasts. It could serve as a promising drug of PF.


Assuntos
Berberina , Proliferação de Células , Fibroblastos , Pulmão , Miofibroblastos , Humanos , Proliferação de Células/efeitos dos fármacos , Berberina/farmacologia , Berberina/análogos & derivados , Miofibroblastos/efeitos dos fármacos , Pulmão/patologia , Pulmão/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Inflamação/tratamento farmacológico , Fator 2 Relacionado a NF-E2/metabolismo , Fibrose Pulmonar/tratamento farmacológico , Fator de Crescimento Transformador beta1/metabolismo , Linhagem Celular , Coptis , Heme Oxigenase-1/metabolismo , Transdução de Sinais/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Diferenciação Celular/efeitos dos fármacos , Anti-Inflamatórios/farmacologia
8.
World J Pediatr ; 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38970731

RESUMO

BACKGROUND: Congenital anomalies of the kidneys and urinary tract (CAKUT) are the most common cause of prenatally diagnosed developmental malformation. This study aimed to assess the relationship between maternal diseases and CAKUT in offspring. METHODS: This retrospective study enrolled all pregnant women registered from January 2020 to December 2022 at one medical center. Medical information on maternal noncommunicable diseases, including obesity, hypertension, diabetes mellitus, kidney disease, hyperthyroidism, hypothyroidism, psychiatric disease, epilepsy, cancer, and autoimmune disease was collected. Based on the records of ultrasound scanning during the third trimester, the diagnosis was classified as isolated urinary tract dilation (UTD) or kidney anomalies. Multivariate logistic regression was performed to establish models to predict antenatal CAKUT. RESULTS: Among the 19,656 pregnant women, perinatal ultrasound detected suspicious CAKUT in 114 (5.8/1000) fetuses, comprising 89 cases with isolated UTD and 25 cases with kidney anomalies. The risk of antenatal CAKUT was increased in the fetuses of mothers who experienced gestational diabetes, thyroid dysfunction, neuropsychiatric disease, anemia, ovarian and uterine disorders. A prediction model for isolated UTD was developed utilizing four confounding factors, namely gestational diabetes, gestational hypertension, maternal thyroid dysfunction, and hepatic disease. Similarly, a separate prediction model for kidney anomalies was established based on four distinct confounding factors, namely maternal thyroid dysfunction, gestational diabetes, disorders of ovarian/uterine, and kidney disease. CONCLUSIONS: Isolated UTD and kidney anomalies were associated with different maternal diseases. The results may inform the clinical management of pregnancy and highlight potential differences in the genesis of various subtypes of CAKUT.

9.
Meat Sci ; 216: 109581, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38970933

RESUMO

This study aimed to assess the effect of dietary arginine supplementation on muscle structure and meat characteristics of lambs also considering lipid oxidation products and to contribute to reveal its mechanisms of action using tandem mass tagging (TMT) proteomics. Eighteen lambs were allocated to two dietary treatment groups: control diet or control diet with the addition of 1% L-arginine. The results revealed that dietary arginine supplementation increased muscle fibre diameter and cross-sectional area (P < 0.05), which was attributable to protein deposition, as evidenced by increased RNA content, RNA/DNA ratio, inhibition of apoptotic enzyme activity, and alterations in the IGF-1/Akt signaling pathway (P < 0.05). In addition, dietary arginine elevated pH24h, a* values, and IMF content, decreased shear force value and backfat thickness (P < 0.05), as well as decreased the formation of lipid oxidation products involved in meat flavor including hexanal, heptanal, octanal, nonanal and 1-octen-3-ol by increasing the antioxidant capacity of the muscle (P < 0.05). The proteomics results suggested that seven enrichment pathways may be potential mechanisms by which arginine affected the muscle structure and meat characteristics of lambs. In summary, arginine supplementation in lamb diets provides a safe and effective way to improve meat quality, and antioxidant capacity of muscle of lamb.

10.
FASEB J ; 38(13): e23766, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38967214

RESUMO

Dysbiosis of gut microbiota may account for pathobiology in simple fatty liver (SFL), metabolic dysfunction-associated steatohepatitis (MASH), fibrotic progression, and transformation to MASH-associated hepatocellular carcinoma (MASH-HCC). The aim of the present study is to investigate gut dysbiosis in this progression. Fecal microbial rRNA-16S sequencing, absolute quantification, histopathologic, and biochemical tests were performed in mice fed high fat/calorie diet plus high fructose and glucose in drinking water (HFCD-HF/G) or control diet (CD) for 2, 16 weeks, or 14 months. Histopathologic examination verified an early stage of SFL, MASH, fibrotic, or MASH-HCC progression with disturbance of lipid metabolism, liver injury, and impaired gut mucosal barrier as indicated by loss of occludin in ileum mucosa. Gut dysbiosis occurred as early as 2 weeks with reduced α diversity, expansion of Kineothrix, Lactococcus, Akkermansia; and shrinkage in Bifidobacterium, Lactobacillus, etc., at a genus level. Dysbiosis was found as early as MAHS initiation, and was much more profound through the MASH-fibrotic and oncogenic progression. Moreover, the expansion of specific species, such as Lactobacillus johnsonii and Kineothrix alysoides, was confirmed by an optimized method for absolute quantification. Dynamic alterations of gut microbiota were characterized in three stages of early SFL, MASH, and its HCC transformation. The findings suggest that the extent of dysbiosis was accompanied with MASH progression and its transformation to HCC, and the shrinking or emerging of specific microbial species may account at least in part for pathologic, metabolic, and immunologic alterations in fibrogenic progression and malignant transition in the liver.


Assuntos
Carcinoma Hepatocelular , Disbiose , Microbioma Gastrointestinal , Neoplasias Hepáticas , Camundongos Endogâmicos C57BL , Animais , Camundongos , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/microbiologia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/etiologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/microbiologia , Neoplasias Hepáticas/etiologia , Disbiose/microbiologia , Masculino , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Fígado Gorduroso/microbiologia , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Progressão da Doença , Metabolismo dos Lipídeos , Fígado/metabolismo , Fígado/patologia
11.
Artigo em Inglês | MEDLINE | ID: mdl-38980785

RESUMO

Under low data regimes, few-shot object detection (FSOD) transfers related knowledge from base classes with sufficient annotations to novel classes with limited samples in a two-step paradigm, including base training and balanced fine-tuning. In base training, the learned embedding space needs to be dispersed with large class margins to facilitate novel class accommodation and avoid feature aliasing while in balanced fine-tuning properly concentrating with small margins to represent novel classes precisely. Although obsession with the discrimination and representation dilemma has stimulated substantial progress, explorations for the equilibrium of class margins within the embedding space are still in full swing. In this study, we propose a class margin optimization scheme, termed explicit margin equilibrium (EME), by explicitly leveraging the quantified relationship between base and novel classes. EME first maximizes base-class margins to reserve adequate space to prepare for novel class adaptation. During fine-tuning, it quantifies the interclass semantic relationships by calculating the equilibrium coefficients based on the assumption that novel instances can be represented by linear combinations of base-class prototypes. EME finally reweights margin loss using equilibrium coefficients to adapt base knowledge for novel instance learning with the help of instance disturbance (ID) augmentation. As a plug-and-play module, EME can also be applied to few-shot classification. Consistent performance gains upon various baseline methods and benchmarks validate the generality and efficacy of EME. The code is available at github.com/Bohao-Lee/EME.

12.
Cancer Cell ; 42(7): 1268-1285.e7, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38981439

RESUMO

Expanding the efficacy of immune checkpoint blockade (ICB) in colorectal cancer (CRC) presses for a comprehensive understanding of treatment responsiveness. Here, we analyze multiple sequential single-cell samples from 22 patients undergoing PD-1 blockade to map the evolution of local and systemic immunity of CRC patients. In tumors, we identify coordinated cellular programs exhibiting distinct response associations. Specifically, exhausted T (Tex) or tumor-reactive-like CD8+ T (Ttr-like) cells are closely related to treatment efficacy, and Tex cells show correlated proportion changes with multiple other tumor-enriched cell types following PD-1 blockade. In addition, we reveal the less-exhausted phenotype of blood-associated Ttr-like cells in tumors and find that their higher abundance suggests better treatment outcomes. Finally, a higher major histocompatibility complex (MHC) II-related signature in circulating CD8+ T cells at baseline is linked to superior responses. Our study provides insights into the spatiotemporal cellular dynamics following neoadjuvant PD-1 blockade in CRC.


Assuntos
Linfócitos T CD8-Positivos , Neoplasias Colorretais , Imunoterapia , Análise de Célula Única , Humanos , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/terapia , Neoplasias Colorretais/patologia , Análise de Célula Única/métodos , Linfócitos T CD8-Positivos/imunologia , Imunoterapia/métodos , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Linfócitos do Interstício Tumoral/imunologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Masculino , Feminino
14.
Artigo em Inglês | MEDLINE | ID: mdl-38995185

RESUMO

The intestines of mice are colonized by diverse, as-yet-uncultivated bacteria. In this report, we describe the isolation, culture, genotypic and phenotypic characterization, as well as taxonomic classification of three novel anaerobic bacterial strains derived from the caecal contents of C57BL/6J male mice. According to the phenotypic and genotype-based polyphasic taxonomy, we propose three novel species within the family Oscillospiraceae. They are Acutalibacter caecimuris sp. nov. (type strain M00118T=CGMCC 1.18042T=KCTC 25739T), Acutalibacter intestini sp. nov. (type strain M00204T=CGMCC 1.18044T=KCTC 25741T) and Neglectibacter caecimuris sp. nov. (type strain M00184T=CGMCC 1.18043T=KCTC 25740T).


Assuntos
Técnicas de Tipagem Bacteriana , Ceco , DNA Bacteriano , Camundongos Endogâmicos C57BL , Filogenia , RNA Ribossômico 16S , Análise de Sequência de DNA , Animais , Masculino , Ceco/microbiologia , Camundongos , RNA Ribossômico 16S/genética , DNA Bacteriano/genética , Ácidos Graxos/química , Composição de Bases
15.
Bioact Mater ; 40: 261-274, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38973991

RESUMO

Artificial skin involves multidisciplinary efforts, including materials science, biology, medicine, and tissue engineering. Recent studies have aimed at creating skins that are multifunctional, intelligent, and capable of regenerating tissue. In this work, we present a specialized 3D printing ink composed of polyurethane and bioactive glass (PU-BG) and prepare dual-function skin patch by microfluidic-regulated 3D bioprinting (MRBP) technique. The MRBP endows the skin patch with a highly controlled microstructure and superior strength. Besides, an asymmetric tri-layer is further constructed, which promotes cell attachment and growth through a dual transport mechanism based on hydrogen bonds and gradient structure from hydrophilic to superhydrophilic. More importantly, by combining the features of biomedical skin with electronic skin (e-skin), we achieved a biomedical and electronic dual-function skin patch. In vivo experiments have shown that this skin patch can enhance hemostasis, resist bacterial growth, stimulate the regeneration of blood vessels, and accelerate the healing process. Meanwhile, it also mimics the sensory functions of natural skin to realize signal detection, where the sensitivity reached up to 5.87 kPa-1, as well as cyclic stability (over 500 cycles), a wide detection range of 0-150 kPa, high pressure resolution of 0.1 % under the pressure of 100 kPa. This work offers a versatile and effective method for creating dual-function skin patches and provide new insights into wound healing and tissue repair, which have significant implications for clinical applications.

16.
Dev Psychol ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38976436

RESUMO

Previous work has examined the impact of prenatal illicit drug use (PDU) on children's problem behaviors. However, many PDU-related risk factors, including genetic and rearing environmental risks, can also influence offspring's problem behaviors, thus confounding PDU, genetic, and rearing environmental influences. This study aimed to (a) identify effects of PDU on school-aged children's problem behaviors, including both externalizing and internalizing behaviors at Age 7, after controlling genetic and specific rearing environmental (e.g., maternal and paternal hostility at Ages 4.5 and 6) influences and (b) examine interaction effects between PDU and maternal and paternal hostility in predicting children's problem behaviors at Age 7. We used a parent-offspring adoption design to partition genetic and prenatal effects from postnatal rearing environmental influences. Participants were 561 children adopted at birth (42% female; 56% White, 19% multiracial, 13% Black/African American, 11% Latine, and 1% other), their adoptive parents, and their birth parents. Results indicate that PDU did not show a direct impact on Age 7 problem behaviors before or after controlling genetic risks and adoptive mother's and father's hostility. However, we found significant interactions between adoptive father's hostility and PDU when predicting children's problem behaviors, such that higher paternal hostility was associated with higher externalizing and internalizing behaviors for children whose birth mothers were non-use or rare use of illicit drugs during pregnancy. The results suggest that different from non- or rare drug-exposed children, higher levels of PDU may override the effects of paternal hostility, but not maternal hostility, on problem behaviors at Age 7. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

17.
Exp Biol Med (Maywood) ; 249: 10142, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38993197

RESUMO

The cornea is an avascular tissue in the eye that has multiple functions in the eye to maintain clear vision which can significantly impair one's vision when subjected to damage. Peroxisome proliferator-activated receptors (PPARs), a family of nuclear receptor proteins comprising three different peroxisome proliferator-activated receptor (PPAR) isoforms, namely, PPAR alpha (α), PPAR gamma (γ), and PPAR delta (δ), have emerged as potential therapeutic targets for treating corneal diseases. In this review, we summarised the current literature on the therapeutic effects of PPAR agents on corneal diseases. We discussed the role of PPARs in the modulation of corneal wound healing, suppression of corneal inflammation, neovascularisation, fibrosis, stimulation of corneal nerve regeneration, and amelioration of dry eye by inhibiting oxidative stress within the cornea. We also discussed the underlying mechanisms of these therapeutic effects. Future clinical trials are warranted to further attest to the clinical therapeutic efficacy.


Assuntos
Doenças da Córnea , Receptores Ativados por Proliferador de Peroxissomo , Humanos , Doenças da Córnea/tratamento farmacológico , Doenças da Córnea/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/agonistas , Animais , Cicatrização/efeitos dos fármacos , Córnea/metabolismo , Estresse Oxidativo/efeitos dos fármacos
18.
PLoS Biol ; 22(7): e3002679, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38995985

RESUMO

Over-generalized fear is a maladaptive response to harmless stimuli or situations characteristic of posttraumatic stress disorder (PTSD) and other anxiety disorders. The dorsal dentate gyrus (dDG) contains engram cells that play a crucial role in accurate memory retrieval. However, the coordination mechanism of neuronal subpopulations within the dDG network during fear generalization is not well understood. Here, with the Tet-off system combined with immunostaining and two-photon calcium imaging, we report that dDG fear engram cells labeled in the conditioned context constitutes a significantly higher proportion of dDG neurons activated in a similar context where mice show generalized fear. The activation of these dDG fear engram cells encoding the conditioned context is both sufficient and necessary for inducing fear generalization in the similar context. Activities of mossy cells in the ventral dentate gyrus (vMCs) are significantly suppressed in mice showing fear generalization in a similar context, and activating the vMCs-dDG pathway suppresses generalized but not conditioned fear. Finally, modifying fear memory engrams in the dDG with "safety" signals effectively rescues fear generalization. These findings reveal that the competitive advantage of dDG engram cells underlies fear generalization, which can be rescued by activating the vMCs-dDG pathway or modifying fear memory engrams, and provide novel insights into the dDG network as the neuronal basis of fear generalization.


Assuntos
Giro Denteado , Medo , Neurônios , Animais , Medo/fisiologia , Giro Denteado/fisiologia , Camundongos , Masculino , Neurônios/fisiologia , Neurônios/metabolismo , Camundongos Endogâmicos C57BL , Condicionamento Clássico/fisiologia , Memória/fisiologia , Generalização Psicológica/fisiologia
19.
Ecotoxicol Environ Saf ; 282: 116711, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-39002383

RESUMO

Silicosis, caused by silica exposure, is the most widespread and deadliest occupational disease. However, effective treatments are lacking. Therefore, it is crucial to elucidate the mechanisms and targets involved in the development of silicosis. We investigated the basic processes of silicosis development and onset at different exposure durations (2 or 4 weeks) using various techniques such as histopathology, immunohistochemistry, Enzyme linked immunosorbent assay(ELISA),16 S rRNA, and untargeted metabolomics.These results indicate that exposure to silica leads to progressive damage to lung tissue with significant deterioration observed over time. Time-dependent cytokines such as the IL-4, IL-13, and IL-6 are detected in lung lavage fluid, the model group consistently exhibited elevated levels of these cytokines, indicating a persistent and worsening inflammatory response in the lungs. Meanwhile, HE and Masson results show that 4-week exposure to silica causes more obvious lung injury and pulmonary fibrosis. Besides, the model group consistently exhibited a distinct lung bacterial population, known as the Lachnospiraceae_NK4A136_group, regardless of exposure duration. However, with increasing exposure duration, specific temporal changes were observed in lung bacterial populations, including Haliangium, Allobaculum, and Sandaracinus (at 4 weeks; p < 0.05). Furthermore, our study revealed a strong correlation between the mechanism of silica-induced lung injury and three factors: oxidative stress, impaired lipid metabolism, and imbalanced amino acid metabolism. We observed a close correlation between cytokine levels, changes in lung microbiota, and metabolic disturbances during various exposure periods. These findings propose that a possible mechanism of silica-induced lung injury involves the interplay of cytokines, lung microbiota, and metabolites.

20.
Med Sci Monit ; 30: e943955, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38985697

RESUMO

Deep vein thrombosis (DVT) of the lower extremities is divided into 2 categories according to the extent of thrombosis involvement. Thrombosis involving the popliteal vein, femoral vein, and iliac vein is classified as proximal DVT, while thrombosis involving the anterior tibial vein, posterior tibial vein, peroneal vein, and calf muscles vein is regarded as distal DVT. There are updated guidelines for the anticoagulant treatment for proximal DVT, but the best anticoagulant treatment for distal DVT is still controversial, especially for isolated calf muscular vein thrombosis (CMVT). The risk of isolated CMVT extending to the proximal deep veins and developing into pulmonary embolism is lower than with distal DVT. Some scholars believe that isolated CMVT has the risk of evolving into proximal deep vein thrombosis and pulmonary embolism, and active early anticoagulation therapy can reduce the risk and benefit patients. In addition, based on the characteristics of CMVT and the bleeding risk of anticoagulation therapy, some studies have recommended use of non-anticoagulation methods such as compression therapy. There is still a lack of multicenter, big-data, randomized, controlled trials on the benefits or risks of anticoagulation therapy. Among scholars who support anticoagulation therapy, there is still a lack of consensus on the optimal duration. This article reviews the current evidence on anticoagulant therapy for patients with isolated CMVT and how long the anticoagulation course should be if anticoagulation is required. Our research will provide a theoretical basis for subsequent research. More prospective studies with larger sample sizes are needed to provide more clinical evidence.


Assuntos
Anticoagulantes , Perna (Membro) , Trombose Venosa , Humanos , Anticoagulantes/uso terapêutico , Trombose Venosa/tratamento farmacológico , Perna (Membro)/irrigação sanguínea , Músculo Esquelético/irrigação sanguínea , Embolia Pulmonar/tratamento farmacológico
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