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1.
Cell Commun Signal ; 22(1): 456, 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39327570

RESUMO

BACKGROUND: C-X-C receptor 4(CXCR4) is widely considered to be a highly conserved G protein-coupled receptor, widely involved in the pathophysiological processes in the human body, including fibrosis. However, its role in regulating macrophage-related inflammation in the fibrotic process of prostatitis has not been confirmed. Here, we aim to describe the role of CXCR4 in modulating macrophage M1 polarization through glycolysis in the development of prostatitis fibrosis. METHODS: Use inducible experimental chronic prostatitis as a model of prostatic fibrosis. Reduce CXCR4 expression in immortalized bone marrow-derived macrophages using lentivirus. In the fibrotic mouse model, use adenovirus carrying CXCR4 agonists to detect the silencing of CXCR4 and assess the in vivo effects. RESULTS: In this study, we demonstrated that reducing CXCR4 expression during LPS treatment of macrophages can alleviate M1 polarization. Silencing CXCR4 can inhibit glycolytic metabolism, enhance mitochondrial function, and promote macrophage transition from M1 to M2. Additionally, in vivo functional experiments using AAV carrying CXCR4 showed that blocking CXCR4 in experimental autoimmune prostatitis (EAP) can alleviate inflammation and experimental prostate fibrosis development. Mechanistically, CXCR4, a chemokine receptor, when silenced, weakens the PI3K/AKT/mTOR pathway as its downstream signal, reducing c-MYC expression. PFKFB3, a key enzyme involved in glucose metabolism, is a target gene of c-MYC, thus impacting macrophage polarization and glycolytic metabolism processes.


Assuntos
Fibrose , Glicólise , Macrófagos , Próstata , Receptores CXCR4 , Masculino , Animais , Receptores CXCR4/metabolismo , Receptores CXCR4/genética , Macrófagos/metabolismo , Camundongos , Próstata/patologia , Próstata/metabolismo , Prostatite/patologia , Prostatite/metabolismo , Prostatite/genética , Transdução de Sinais , Camundongos Endogâmicos C57BL , Humanos , Serina-Treonina Quinases TOR/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Polaridade Celular , Fosfatidilinositol 3-Quinases/metabolismo , Fosfofrutoquinase-2/metabolismo , Fosfofrutoquinase-2/genética
2.
Front Microbiol ; 15: 1445304, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39323879

RESUMO

Background: The gut microbiota has been demonstrated to have a significant role in the pathogenesis and progression of a variety of diseases, including prostate cancer, prostatitis, and benign prostatic hyperplasia. Potential links between prostate diseases, immune cells and the gut microbiota have not been adequately investigated. Methods: MR studies were conducted to estimate the effects of instrumental variables obtained from genome-wide association studies (GWASs) of 196 gut microbial taxa and 731 immune cells on the risk of prostate diseases. The primary method for analysing causal relationships was inverse variance-weighted (IVW) analysis, and the MR results were validated through various sensitivity analyses. Results: MR analysis revealed that 28 gut microbiome taxa and 75 immune cell types were significantly associated with prostate diseases. Furthermore, reverse MR analysis did not support a causal relationship between prostate diseases and the intestinal microbiota or immune cells. Finally, the results of the mediation analysis indicated that Secreting Treg % CD4 Treg, Activated & resting Treg % CD4 Treg, and Mo MDSC AC inhibited the role of the class Mollicutes in reducing the risk of PCa. In prostatitis, CD8+ T cells on EM CD8br hinder the increased risk associated with the genus Eubacterium nodatum group. Interestingly, in BPH, CD28- CD25++CD8br AC and CD16-CD56 on HLA DR+ NK promoted the role of the genus Dorea in reducing the risk of BPH. Conclusion: This study highlights the complex relationships among the gut microbiota, immune cells and prostate diseases. The involvement of the gut microbiota in regulating immune cells to impact prostate diseases could provide novel methods and concepts for its therapy and management.

3.
Fish Shellfish Immunol ; 154: 109902, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39276814

RESUMO

The Penaeus vannamei aquaculture industry is facing a significant challenge in the form of hepatopancreatic microsporidiosis (HPM) caused by Enterocytozoon hepatopenaei (EHP), resulting in substantial economic losses. However, the extent of knowledge regarding the mechanisms by which shrimp resist EHP is limited. We screened resistant and susceptible shrimp and found that resistant shrimp had lower EHP load and less tissue damage. To gain insight into the molecular mechanisms underlying the EHP resistance of shrimp, a comparison was conducted at the transcriptional level between the resistant and susceptible families. Transcriptomic analysis of shrimp hepatopancreas revealed significant differences between the resistant and susceptible families. Compared to the susceptible family, the immune system of the resistant family was activated. The resistant family showed up-regulation in the expression of cathepsin L, C-type lectin, penaeidin, chitinase genes, and metabolism of xenobiotics by cytochrome P450-related genes. Additionally, the resistant shrimp exhibited a higher capacity for amino acid uptake. The observed differences in the resistant and susceptible family transcriptome may contribute to the shrimp's resistance to EHP.

4.
Theor Appl Genet ; 137(10): 225, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39287784

RESUMO

KEY MESSAGE: We identified a 580 bp deletion of CmaKNAT6 coding region influences peel colour of mature Cucurbita maxima fruit. Peel colour is an important agronomic characteristic affecting commodity quality in Cucurbit plants. Genetic mapping of fruit peel colour promotes molecular breeding and provides an important basis for understanding the regulatory mechanism in Cucurbit plants. In the present study, the Cucurbita maxima inbred line '9-6' which has a grey peel colour and 'U3-3-44' which has a dark green peel colour in the mature fruit stage, were used as plant materials. At 5-40 days after pollination (DAP), the contents of chlorophyll a, chlorophyll b, total chlorophyll and carotenoids in the 'U3-3-44' peels were significantly greater than those in the '9-6' peels. In the epicarp of the '9-6' mature fruit, the presence of nonpigmented cell layers and few chloroplasts in each cell in the pigmented layers were observed. Six generations derived by crossing '9-6' and 'U3-3-44' were constructed, and the dark green peel was found to be controlled by a single dominant locus, which was named CmaMg (mature green peel). Through bulked-segregant analysis sequencing (BSA-seq) and insertion-deletion (InDel) markers, CmaMg was mapped to a region of approximately 449.51 kb on chromosome 11 using 177 F2 individuals. Additionally, 1703 F2 plants were used for fine mapping to compress the candidate interval to a region of 32.34 kb. Five coding genes were in this region, and CmaCh11G000900 was identified as a promising candidate gene according to the reported function, sequence alignment, and expression analyses. CmaCh11G000900 (CmaKNAT6) encodes the homeobox protein knotted-1-like 6 and contains 4 conserved domains. CmaKNAT6 of '9-6' had a 580 bp deletion, leading to premature transcriptional termination. The expression of CmaKNAT6 tended to increase sharply during the early fruit development stage but decrease gradually during the late period of fruit development. Allelic diversity analysis of pumpkin germplasm resources indicated that the 580 bp deletion in the of CmaKNAT6 coding region was associated with peel colour. Subcellular localization analysis indicated that CmaKNAT6 is a nuclear protein. Transcriptomic analysis of the inbred lines '9-6' and 'U3-3-44' indicated that genes involved in chlorophyll biosynthesis were more enriched in 'U3-3-44' than in '9-6'. Additionally, the expression of transcription factor genes that positively regulate chlorophyll synthesis and light signal transduction pathways was upregulated in 'U3-3-44'. These results lay a foundation for further studies on the genetic mechanism underlying peel colour and for optimizing peel colour-based breeding strategies for C. maxima.


Assuntos
Mapeamento Cromossômico , Cucurbita , Frutas , Perfilação da Expressão Gênica , Pigmentação , Cucurbita/genética , Cucurbita/crescimento & desenvolvimento , Frutas/genética , Frutas/crescimento & desenvolvimento , Pigmentação/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fenótipo , Regulação da Expressão Gênica de Plantas , Clorofila/metabolismo , Genes de Plantas , Carotenoides/metabolismo
5.
Small ; : e2406179, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39221682

RESUMO

For BixSb2- xTe3 (BST) in thermoelectric field, the element ratio is easily influenced by the chemical environment, deviating from the stoichiometric ratio and giving rise to various intrinsic defects. In P-type polycrystalline BST, SbTe and BiTe are the primary forms of defects. Defect engineering is a crucial strategy for optimizing the electrical transport performance of Bi2Te3-based materials, but achieving synchronous improvement of thermal performance is challenging. In this study, mesoporous SiO2 is utilized to successfully mitigate the adverse impacts of vacancy defects, resulting in an enhancement of the electrical transport performance and a pronounced reduction in thermal conductivity. Crystal and the microstructure of the continuous modulation contribute to the effective phonon-electronic decoupling. Ultimately, the peak zT of Bi0.4Sb1.6Te3/0.8 wt% SiO2 (with a pore size of 4 nm) nanocomposites reaches as high as 1.5 at 348 K, and a thermoelectric conversion efficiency of 6.6% is achieved at ΔT = 222.7 K. These results present exciting possibilities for the realization of defect regulation in porous materials and hold reference significance for other material systems.

6.
J Contam Hydrol ; 267: 104426, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39270601

RESUMO

At present, as the problem of water shortage and pollution is growing serious, it is particularly important to understand the recycling and treatment of wastewater. Artificial intelligence (AI) technology is characterized by reliable mapping of nonlinear behaviors between input and output of experimental data, and thus single/integrated AI model algorithms for predicting different pollutants or water quality parameters have become a popular method for simulating the process of wastewater treatment. Many AI models have successfully predicted the removal effects of pollutants in different wastewater treatment processes. Therefore, this paper reviews the applications of artificial intelligence technologies such as artificial neural networks (ANN), adaptive network-based fuzzy inference system (ANFIS) and support vector machine (SVM). Meanwhile, this review mainly introduces the effectiveness and limitations of artificial intelligence technology in predicting different pollutants (dyes, heavy metal ions, antibiotics, etc.) and different water quality parameters such as biochemical oxygen demand (BOD), chemical oxygen demand (COD), total nitrogen (TN) and total phosphorus (TP) in wastewater treatment process, involving single AI model and integrated AI model. Finally, the problems that need further research together with challenges ahead in the application of artificial intelligence models in the field of environment are discussed and presented.

7.
Int J Biol Macromol ; 278(Pt 1): 134624, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39134191

RESUMO

The molecular chaperone GroEL, commonly found in various bacterial species, exhibits heightened expression levels in response to high temperatures and increased levels of oxygen free radicals. Limited literature currently exists on the probiotic role of GroEL in invertebrates. This study sought to explore how the surface protein GroEL from Lactobacillus plantarum Ep-M17 impacts the intestinal barrier function of Penaeus vannamei. Through pull-down and immunofluorescence assays, the interaction between GroEL and Act1 in the gastrointestinal tract of P. vannamei was confirmed. Results from bacterial binding assays demonstrated that rGroEL can bind to pathogens like Vibrio parahaemolyticus E1 (V. p-E1). In vitro experiments revealed that the administration of rGroEL significantly decreased the levels of inflammatory cytokines induced by pathogens while preserving the integrity of tight junctions between intestinal epithelial cells and reducing bacteria-induced apoptosis. Additionally, rGroEL notably lessened the intestinal loading of V. p-E1 in P. vannamei, downregulated immune-related gene expression, and upregulated BCL/BAX expression in the intestines following V. p-E1 challenge. Mechanistic investigations further showed that rGroEL treatment effectively suppressed the expression and phosphorylation of proteins involved in the NF-κB and PI3K-AKT-mTOR signalling pathways in the intestines of bacteria-infected P. vannamei. Furthermore, GroEL reinforces protection against bacterial infections by enhancing the phagocytic and anti-apoptotic capabilities of P. vannamei hemocytes. These results suggest that GroEL may impede the interaction between pathogens and the intestinal mucosa through its competitive binding characteristics, ultimately reducing bacterial infections.


Assuntos
Chaperonina 60 , Mucosa Intestinal , Penaeidae , Vibrio parahaemolyticus , Animais , Chaperonina 60/metabolismo , Penaeidae/microbiologia , Penaeidae/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Transdução de Sinais/efeitos dos fármacos , Intestinos/microbiologia , Lactobacillus plantarum/metabolismo , Apoptose/efeitos dos fármacos , Proteínas de Bactérias/metabolismo , Lactobacillales/metabolismo
8.
Ecotoxicol Environ Saf ; 284: 116926, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39205350

RESUMO

Metal-organic frameworks (MOFs) exhibit high chemical stability and porosity, and have been widely applied in various fields including selective adsorption and separation, sensors, and catalysis. When combined with Fe3O4, they effectively address issues such as aggregation of Fe3O4 particles and the difficulty in recovering MOFs as catalysts. Therefore, in this study, we used a simple solvothermal method as a catalyst to synthesize a high specific surface area magnetic composite Fe3O4@MOF-74, which was used to catalyze the degradation of bisphenol A (BPA) and amino black 10B in wastewater. We activated Na2S2O8 to generate radicals for oxidizing and degrading BPA and amino black 10B. Experimental results showed that at 35 °C, with Fe3O4@MOF-74 (Fe3O4: MOF-74=1:1) concentration of 0.2 g/L and Na2S2O8 concentration of 2 g/L, the catalytic effect is efficient and economical. Meanwhile, removal rates of BPA and amino black 10B exceeded 95.58 % over a broad pH range (pH 3-9). Furthermore, even after multiple cycles of use, Fe3O4@MOF-74 maintained catalytic degradation rates of BPA and amino black 10B above 93.24 % and 95.01 %, respectively. Additionally, in water samples, removal rates of BPA and amino black 10B exceeded 91.55 %. This study provides a new and efficient catalyst material for wastewater treatment, which is expected to play an important role in environmental remediation.


Assuntos
Compostos Benzidrílicos , Estruturas Metalorgânicas , Fenóis , Poluentes Químicos da Água , Compostos Benzidrílicos/química , Fenóis/química , Catálise , Estruturas Metalorgânicas/química , Poluentes Químicos da Água/química , Águas Residuárias/química , Adsorção
9.
Zhonghua Nan Ke Xue ; 30(5): 444-449, 2024 May.
Artigo em Chinês | MEDLINE | ID: mdl-39210495

RESUMO

Prostatitis is one of the three most common prostate diseases in men, the other two being prostatic hyperplasia and prostate cancer, and about 50% of men worldwide have been attacked by prostatitis during their lives. The incidence of infertility is significantly higher in patients with chronic prostatitis / chronic pelvic pain syndrome (CP/CPPS) than in those without it, which is mainly attributed to the changed semen composition of the CP/CPPS patients. Using the key words chronic prostatitis, chronic pelvic pain syndrome, sperm, semen, and seminal plasma, we searched PubMed and Medical Lines online for originals, review articles, clinical trials, case reports and associated citations on humans and animals published up to 2024. We comprehensively reviewed the previous studies and investigations relating chronic prostatitis, seminal plasma change and sperm quality, and discussed the impact of the change of semen composition on sperm quality.


Assuntos
Dor Pélvica , Prostatite , Sêmen , Espermatozoides , Humanos , Masculino , Análise do Sêmen , Doença Crônica , Dor Crônica , Infertilidade Masculina/etiologia , Motilidade dos Espermatozoides
10.
Environ Pollut ; 359: 124556, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39025291

RESUMO

Ground ozone (O3) pollution has emerged as a prominent environmental concern in eastern cities of China, particularly during the summer and autumn seasons. However, a comprehensive investigation into the three-dimensional (3-D) evolution characteristics of O3 within complicated urban environments, especially in lake-land environment, is notably scarce. To enhance our understanding of the mechanisms underlying elevated O3 concentrations within a 3-D scale, this study employed an ozone lidar to delineate vertical ozone profiles in Changzhou, a typical city in China with complicated anthropogenic and biogenic emissions and complex land cover. The process analysis tool integrated into the Weather Research and Forecasting with Chemistry (WRF-Chem) model was further utilized to analyze the formation processes of O3. The results unveil a persistent O3 pollution episode lasting over 15 days in Changzhou during the study period, with multiple peaks exceeding 200 µg m⁻³. Notably, O3 predominantly accumulated within the boundary layer, confined below 1.2 km. Both ground and vertical contributions to this pollution were mainly due to local chemical reactions, with a maximum near-surface contribution reaching 19 ppb h-1 and a vertical contribution of 10 ppb h-1 at the height of 900 ± 200 m. Furthermore, episodes of the enhanced O3 concentrations on August 9 and August 26, 2021, were influenced by external advection process. Our study also found that local circulation plays an important role in the accumulation of surface O3 during certain periods. There was a temperature difference between the surface of Lake Tai and the adjacent land, resulting in the formation of lake-land breezes that facilitate the transport of O3 from the lake surface to the terrestrial environment during pollution events. Our study emphasizes the necessity of reducing local pollutant emissions and implementing joint emission controls as the primary strategies for mitigating O3 pollution in Changzhou and the surrounding region.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Monitoramento Ambiental , Ozônio , Ozônio/análise , China , Poluentes Atmosféricos/análise , Poluição do Ar/estatística & dados numéricos , Estações do Ano , Cidades , Modelos Químicos
11.
Int J Surg ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38954665

RESUMO

BACKGROUND: The main aim of this study was to examine the perioperative results of reoperations and suggest novel surgical approaches. Based on a substantial number of robotic and laparoscopic nephron-sparing surgery (NSS), we aim to propose novel surgical strategies that offer practical recommendations to surgeons. METHODS: Renal cell carcinoma patients with ipsilateral recurrent tumors, without evidence of metastasis, and who underwent primary NSS at our center between 2013 and 2023 were enrolled in this study, and all received the second time surgery. We conducted an analysis to evaluate perioperative outcomes and observed trends over a decade. Additionally, based on the findings from this study, we developed our surgical strategies. RESULTS: In the past decade, our center has successfully conducted a total of 2546 surgeries for renal cell carcinoma, out of which this study includes 15 patients who met the specified criteria. For reoperation, robotic-assisted surgery was applied in 5 cases (33.3%), laparoscopic surgery in 6 cases (40%), and open surgeries in 4 cases (26.7%). While 4 (26.7%) patients underwent NSS while radical nephrectomy was performed on 11 patients (73.3%). The median operative time was 215 minutes (IQR: 135-300), and the median estimated blood loss was 50 ml (IQR: 50-100). The median length of postoperative hospitalization was 6 days (IQR: 5-9). Furthermore, there has been a yearly increase in the application of robotic-assisted NSS at our institution. CONCLUSION: Reoperation following the pNSS is a secure and effective surgical approach. We introduce novel surgical strategies for primary surgery and reoperation, which offer valuable insights to surgeons in current study.

12.
Nat Biomed Eng ; 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38982158

RESUMO

Precisely sensing and guiding cell-state transitions via the conditional genetic activation of appropriate differentiation factors is challenging. Here we show that desired cell-state transitions can be guided via genetically encoded sensors, whereby endogenous cell-state-specific miRNAs regulate the translation of a constitutively transcribed endoribonuclease, which, in turn, controls the translation of a gene of interest. We used this approach to monitor several cell-state transitions, to enrich specific cell types and to automatically guide the multistep differentiation of human induced pluripotent stem cells towards a haematopoietic lineage via endothelial cells as an intermediate state. Such conditional activation of gene expression is durable and resistant to epigenetic silencing and could facilitate the monitoring of cell-state transitions in physiological and pathological conditions and eventually the 'rewiring' of cell-state transitions for applications in organoid-based disease modelling, cellular therapies and regenerative medicine.

13.
Int J Biol Sci ; 20(9): 3393-3411, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38993566

RESUMO

Chronic prostatitis is one of the most common urologic diseases that troubles young men, with unclear etiology and ineffective treatment approach. Pyroptosis is a novel model of cell death, and its roles in chronic prostatitis are unknown. In this study, P2X7R, NEK7, and GSDMD-NT expression levels were detected in prostate tissues from benign prostate hyperplasia (BPH) patients and experiment autoimmune prostatitis (EAP) mice. P2X7R agonist, antagonist, NLRP3 inhibitor, and disulfiram were used to explore the roles of the P2X7R-NEK7-NLRP3 axis in prostate epithelial cell pyroptosis and chronic prostatitis development. We found that P2X7R, NEK7, and GSDMD-NT were highly expressed in the prostate epithelial cells of BPH patients with prostatic inflammation and EAP mice. Activation of P2X7R exacerbated prostatic inflammation and increased NLRP3 inflammasome component expressions and T helper 17 (Th17) cell proportion. Moreover, P2X7R-mediated potassium efflux promoted NEK7-NLRP3 interaction, and NLRP3 assembly and activation, which caused GSDMD-NT-mediated prostate epithelial cell pyroptosis to exacerbate EAP development. Disulfiram could effectively improve EAP by inhibiting GSDMD-NT-mediated prostate epithelial cell pyroptosis. In conclusion, the P2X7R-NEK7-NLRP3 axis could promote GSDMD-NT-mediated prostate epithelial cell pyroptosis and chronic prostatitis development, and disulfiram may be an effective drug to treat chronic prostatitis.


Assuntos
Células Epiteliais , Quinases Relacionadas a NIMA , Proteína 3 que Contém Domínio de Pirina da Família NLR , Proteínas de Ligação a Fosfato , Próstata , Prostatite , Piroptose , Animais , Humanos , Masculino , Camundongos , Doenças Autoimunes/metabolismo , Células Epiteliais/metabolismo , Gasderminas , Camundongos Endogâmicos C57BL , Quinases Relacionadas a NIMA/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteínas de Ligação a Fosfato/metabolismo , Proteínas de Ligação a Poli-ADP-Ribose/metabolismo , Próstata/metabolismo , Prostatite/metabolismo , Piroptose/efeitos dos fármacos , Receptores Purinérgicos P2X7/metabolismo
14.
ACS Appl Mater Interfaces ; 16(31): 41583-41595, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39046871

RESUMO

Conductive hydrogels are widely used in flexible sensors owing to their adjustable structure, good conductivity, and flexibility. The performance of excellent mechanical properties, high sensitivity, and elastic modulus compatible with human tissues is of great interest in the field of flexible sensors. In this paper, the functional groups of trisodium citrate dihydrate (SC) and MXene form multiple hydrogen bonds in the polymer network to prepare a hydrogel with mechanical properties (Young's modulus (23.5-92 kPa) of similar human tissue (0-100 kPa)), sensitivity (stretched GF is 4.41 and compressed S1 is 5.15 MPa-1), and durability (1000 cycles). The hydrogel is able to sensitively detect deformations caused by strain and stress and can be used in flexible sensors to detect human movement in real time such as fingers, wrists, and walking. In addition, the combination of matrix sensing and machine learning was successfully used for handwriting recognition with an accuracy of 0.9744. The combination of machine learning and flexible sensors shows great potential in areas such as healthcare, information security, and smart homes.


Assuntos
Escrita Manual , Hidrogéis , Aprendizado de Máquina , Hidrogéis/química , Humanos , Módulo de Elasticidade , Dispositivos Eletrônicos Vestíveis , Pele/química
15.
Free Radic Biol Med ; 222: 344-360, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38945457

RESUMO

Innovative solutions for rapid protection against broad-spectrum infections are very important in dealing with complex infection environments. We utilized a functionally inactive mutated endolysin protein of Streptococcus pneumoniae (ΔA146Ply) to immunize mice against pneumonic infections by multidrug-resistant bacteria, Candida albicans and influenza virus type A. ΔA146Ply protection relied on both immunized tissue-resident and monocyte-derived alveolar macrophages and inhibited infection induced ferroptosis that upregulated expression of GPX4 (glutathione peroxidase) in alveolar macrophages. Ferroptosis resistance endowed macrophages with enhanced phagocytosis by inhibiting lipid peroxidation during infection. Moreover, we demonstrated ΔA146Ply upregulated GPX4 through the TLR4/IRG1/NRF2 pathway. ΔA146Ply also induced ferroptosis inhibition and phagocytosis improvement in human monocytes. This mode of action is a novel and potentially prophylactic and rapid broad-spectrum anti-infection mechanism. Our study provides new insights into protective interventions that act by regulating ferroptosis to improve multiple pathogen resistance via GPX4 targeting.


Assuntos
Ferroptose , Macrófagos Alveolares , Fator 2 Relacionado a NF-E2 , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Streptococcus pneumoniae , Receptor 4 Toll-Like , Animais , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/genética , Camundongos , Streptococcus pneumoniae/patogenicidade , Ferroptose/genética , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética , Receptor 4 Toll-Like/metabolismo , Receptor 4 Toll-Like/genética , Humanos , Macrófagos Alveolares/metabolismo , Macrófagos Alveolares/imunologia , Macrófagos Alveolares/microbiologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Fagocitose , Candida albicans/patogenicidade , Candidíase/imunologia , Candidíase/genética , Candidíase/microbiologia , Candidíase/metabolismo , Regulação para Cima , Feminino
16.
Transl Oncol ; 47: 102042, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38924847

RESUMO

Clear cell renal cell carcinoma (ccRCC) is a common urological malignancy that is involved in tumor genesis and development. However, few studies have focused on the predictive role of the global histone modification status in ccRCC. A total of 621 patients with complete transcript information and corresponding clinical profiles were obtained from TCGA-KIRC, GSE22541, and EMTAB3267 cohorts. A total of 122 histone modification relevant pathways were derived from MSigDB, and their activation status was quantified using GSVA. Differentially expressed genes (DEGs) were identified and filtrated using univariate Cox regression analysis. The signature was built relied on the least absolute shrinkage and selection operator (LASSO) regression analysis, and evaluated from survival difference, chemotherapy response, and activated pathways. A novel nomogram was established to quantify the probability of death in different patients. Seven risky and fifty-eight protective genes were used in LASSO analysis, and six genes were used to build the histone modification gene (HiMG) signature, which showed significant independent prognostic potential in all three cohorts. The nomogram showed acceptable incremental predictions. CKS2 (p = 0.004) and PD1 (p = 0.002) expression were significantly higher in grade 3 ccRCC than in grades 1-2. CKS2 siRNA in renal cancer cells caused reductions in cellular proliferation, migration, and invasion. Patients with low HiMG may be potential responders to rapamycin, erlotinib and FH535, while AZD6482 and CHIR-99,021 may be more suitable for patients with high HiMG levels. ccRCC histone modification distribution and a clinical signature for prognosis prediction, clinical decision making, and molecular mechanism exploration, were established for risk stratification and personalized treatments.

17.
ACS Appl Mater Interfaces ; 16(25): 32762-32772, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38867400

RESUMO

Currently, the development of hydrogels with excellent mechanical properties (elasticity, fatigue resistance, etc.) and conductive properties can better meet their needs in the field of flexible sensor device applications. Generally, hydrogels with a denser cross-linking density tend to have better mechanical properties, but the improvement in mechanical properties comes at the expense of reduced electrical conductivity. Directly generating CaCO3 in the hydrogel prepolymer can not only increase the cross-linking density of its network but also introduce additional ions to enhance its internal ionic strength, which is beneficial to improving the conductivity of the hydrogel. It is still a big challenge to directly generate CaCO3 in the static prepolymer solution and ensure its uniform dispersion in the hydrogel. Herein, we adopted an improved preparation method to ensure that the directly generated CaCO3 particles can be evenly dispersed in the static prepolymer solution until the polymerization is completed. Finally, a PAM/PVA/CaCO3 hydrogel with supertensile, compressive, toughness, and fatigue resistance properties was prepared. In addition, the presence of free Na+ and Cl- gives the hydrogel excellent conductivity and sensing performance to monitor daily human activities. On the basis of the application of hydrogels in information communication, we have further deepened this application by combining the characteristics of hydrogels themselves. Combined with ASCII code, the hydrogel can also be applied in information exchange and information encryption and decryption, achieving the antitheft function in smart locks. A variety of excellent performance integrated PAM/PVA/CaCO3 hydrogels have broad application prospects for flexible sensors, highlighting great potential in human-computer interaction and intelligent information protection.

18.
Theor Appl Genet ; 137(7): 167, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38909110

RESUMO

KEY MESSAGE: A large fragment deletion of CpAPRR2, encoding a two-component response regulator-like protein, which influences immature white rind color formation in zucchini (Cucurbita pepo). Fruit rind color is an important agronomic trait that affects commodity quality and consumer choice in zucchini (Cucurbita pepo). However, the molecular mechanism controlling rind color is unclear. We characterized two zucchini inbred lines: '19' (dark green rind) and '113' (white rind). Genetic analysis revealed white immature fruit rind color to be controlled by a dominant locus (CpW). Combining bulked segregant analysis sequencing (BSA-seq) and Kompetitive Allele-Specific PCR (KASP) markers, we mapped the CpW locus to a 100.4 kb region on chromosome 5 and then narrow down the candidate region to 37.5 kb using linkage analysis of 532 BC1 and 1613 F2 individuals, including 6 coding genes. Among them, Cp4.1LG05g02070 (CpAPRR2), encoding a two-component response regulator-like protein, was regarded to be a promising candidate gene. The expression level of CpAPRR2 in dark green rind was significantly higher than that in white rind and was induced by light. A deletion of 2227 bp at the 5' end of CpAPRR2 in '113' might explain the white phenotype. Further analysis of allelic diversity in zucchini germplasm resources revealed rind color to be associated with the deletion of CpAPRR2. Subcellular localization analysis indicated that CpAPRR2 was a nuclear protein. Transcriptome analysis using near-isogenic lines with dark green (DG) and white (W) rind indicated that genes involved in photosynthesis and porphyrin metabolism pathways were enriched in DG compared with W. Additionally, chlorophyll synthesis-related genes were upregulated in DG. These results identify mechanisms of zucchini rind color and provide genetic resources for breeding.


Assuntos
Mapeamento Cromossômico , Cucurbita , Frutas , Fenótipo , Pigmentação , Frutas/genética , Frutas/crescimento & desenvolvimento , Pigmentação/genética , Cucurbita/genética , Cucurbita/crescimento & desenvolvimento , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Ligação Genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Alelos , Genes de Plantas , Cor , Transcriptoma
19.
Tuberculosis (Edinb) ; 148: 102530, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38857553

RESUMO

OBJECTIVES: To determine the usefulness of LINC00152 and LARS2-AS1 as potential biomarkers for latent tuberculosis (LTB) and active tuberculosis (ATB), as well as their effect on Mycobacterium (Mtb) infection. METHODS: The expression levels of LINC00152 and LARS2-AS1 in the health, patients with LTB and ATB were detected by qRT-PCR. The ROC curves were constructed to show their potential as biomarkers. The intracellular survival assays for Mtb and the levels of immune-related cytokines were determined to discover the effect of LINC00152 and LARS2-AS1 on Mtb infection. The relationships of miR-485-5p with LINC00152 and LARS2-AS1 were explored. RESULTS: LINC00152 and LARS2-AS1 levels were significantly elevated in patients with ATB and LTB, and Mtb-infected macrophages. LINC00152 and LARS2-AS1 can distinguish the LTB from the health and ATB from LTB. LARS2-AS1 and LINC00152 knock-down reduced the intracellular Mtb survival and induced cellular immune response after Mtb challenge. miR-485-5p was a targeting miRNA for LINC00152 and LARS2-AS1. CONCLUSIONS: LINC00152 and LARS2-AS1 can be considered as potential biomarkers for tuberculosis disease. LINC00152 and LARS2-AS1 have anti-Mtb effects.


Assuntos
Macrófagos , MicroRNAs , Mycobacterium tuberculosis , RNA Longo não Codificante , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Humanos , Macrófagos/imunologia , Macrófagos/microbiologia , Macrófagos/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Mycobacterium tuberculosis/imunologia , Mycobacterium tuberculosis/genética , Masculino , Feminino , Tuberculose Latente/imunologia , Tuberculose Latente/genética , Tuberculose Latente/microbiologia , Tuberculose Latente/diagnóstico , Tuberculose/imunologia , Tuberculose/genética , Tuberculose/microbiologia , Adulto , Estudos de Casos e Controles , Interações Hospedeiro-Patógeno , Pessoa de Meia-Idade , Citocinas/metabolismo , Citocinas/genética , Valor Preditivo dos Testes , Biomarcadores/metabolismo
20.
Materials (Basel) ; 17(10)2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38793383

RESUMO

Intelligent devices, when subjected to multiple interactions, tend to generate electromagnetic pollution, which can disrupt the normal functioning of electronic components. Ferrite, which acts as a microwave-absorbing material (MAM), offers a promising strategy to overcome this issue. To further enhance the microwave absorption properties of ferrite MAM, numerous works have been conducted, including ion doping and combining with other materials. Notably, the microstructure is also key factor that affects the microwave absorption properties of ferrite-based MAM. Thus, this article provides a comprehensive overview of research progress on the influence of the microstructure on ferrite-based MAM. MAMs with sheet and layered structures are also current important research directions. For core-shell structure composites, the solid core-shell structure, hollow core-shell structure, yolk-eggshell structure, and non-spherical core-shell structure are introduced. For porous composites, the biomass porous structure and other porous structures are presented. Finally, the development trends are summarized, and prospects for the structure design and preparation of high-performance MAMs are predicted.

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