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1.
Nat Commun ; 15(1): 5811, 2024 Jul 10.
Article de Anglais | MEDLINE | ID: mdl-38987310

RÉSUMÉ

Extraintestinal Pathogenic Escherichia coli (ExPEC) pose a significant threat to human and animal health. However, the diversity and antibiotic resistance of animal ExPEC, and their connection to human infections, remain largely unexplored. The study performs large-scale genome sequencing and antibiotic resistance testing of 499 swine-derived ExPEC isolates from China. Results show swine ExPEC are phylogenetically diverse, with over 80% belonging to phylogroups B1 and A. Importantly, 15 swine ExPEC isolates exhibit genetic relatedness to human-origin E. coli strains. Additionally, 49 strains harbor toxins typical of enteric E. coli pathotypes, implying hybrid pathotypes. Notably, 97% of the total strains are multidrug resistant, including resistance to critical human drugs like third- and fourth-generation cephalosporins. Correspondingly, genomic analysis unveils prevalent antibiotic resistance genes (ARGs), often associated with co-transfer mechanisms. Furthermore, analysis of 20 complete genomes illuminates the transmission pathways of ARGs within swine ExPEC and to human pathogens. For example, the transmission of plasmids co-harboring fosA3, blaCTX-M-14, and mcr-1 genes between swine ExPEC and human-origin Salmonella enterica is observed. These findings underscore the importance of monitoring and controlling ExPEC infections in animals, as they can serve as a reservoir of ARGs with the potential to affect human health or even be the origin of pathogens infecting humans.


Sujet(s)
Antibactériens , Infections à Escherichia coli , Protéines Escherichia coli , Escherichia coli pathogènes extra-intestinales , Phylogenèse , Maladies des porcs , Animaux , Suidae , Chine/épidémiologie , Escherichia coli pathogènes extra-intestinales/génétique , Escherichia coli pathogènes extra-intestinales/effets des médicaments et des substances chimiques , Escherichia coli pathogènes extra-intestinales/isolement et purification , Escherichia coli pathogènes extra-intestinales/pathogénicité , Infections à Escherichia coli/microbiologie , Infections à Escherichia coli/médecine vétérinaire , Maladies des porcs/microbiologie , Protéines Escherichia coli/génétique , Antibactériens/pharmacologie , Humains , Multirésistance bactérienne aux médicaments/génétique , Plasmides/génétique , Génome bactérien/génétique , Séquençage du génome entier , Tests de sensibilité microbienne , Résistance bactérienne aux médicaments/génétique , bêta-Lactamases/génétique
2.
J Alzheimers Dis ; 2024 Jul 12.
Article de Anglais | MEDLINE | ID: mdl-39031359

RÉSUMÉ

Background: The causal relationships of late-life body mass index (BMI) with Alzheimer's disease (AD) remains debated. Objective: We aimed to assess the associations of dynamic BMI features (ΔBMIs) with cognitive trajectories, AD biomarkers, and incident AD risk. Methods: We analyzed an 8-year cohort of 542 non-demented individuals who were aged ≥65 years at baseline and had BMI measurements over the first 4 years. ΔBMIs were defined as changing extent (change ≤ or >5%), variability (standard deviation), and trajectories over the first 4 years measured using latent class trajectory modeling. Linear mixed-effect models were utilized to examine the influence of ΔBMIs on changing rates of AD pathology biomarkers, hippocampus volume, and cognitive functions. Cox proportional hazards models were used to test the associations with AD risk. Stratified analyzes were conducted by the baseline BMI group and age. Results: Over the 4-year period, compared to those with stable BMI, individuals who experienced BMI decreases demonstrated accelerated declined memory function (p = 0.006) and amyloid-ß deposition (p = 0.034) while BMI increases were associated with accelerated hippocampal atrophy (p = 0.036). Three BMI dynamic features, including stable BMI, low BMI variability, and persistently high BMI, were associated with lower risk of incident AD (p < 0.005). The associations were validated over the 8-year period after excluding incident AD over the first 4 years. No stratified effects were revealed by the BMI group and age. Conclusions: High and stable BMI in late life could predict better cognitive trajectory and lower risk of AD.

3.
Animals (Basel) ; 14(13)2024 Jun 24.
Article de Anglais | MEDLINE | ID: mdl-38997973

RÉSUMÉ

The Hepatitis E virus (HEV) causes acute and chronic Hepatitis E and is a global public health concern. HEV genotypes 3 (HEV-3) and 4 (HEV-4) are common to humans and animals, and domestic pigs and wild boars have been identified as the main reservoirs. However, limited information is available on the status of HEV infection in pigs, particularly in the Guangdong Province, China. This study aimed to investigate the seroprevalence of HEV in pig farms within the Guangdong Province. A total of 1568 serum samples were collected from 25 farms and tested for anti-HEV IgG antibodies. Enzyme-linked immunosorbent assay (ELISA) results revealed that 57.53% (902/1568) of serum samples from 24 farms (24/25, 96%) were positive for anti-HEV IgG antibodies. Year, season, region, and age were all linked risk factors for HEV in Guangdong, with season and region showing more significant impacts. The results showing a high seroprevalence of HEV confirmed its circulation among domestic pigs in the Guangdong Province, China. The presence of this antibody indicates that HEV infection was or is present on farms, posing a risk of zoonotic transmission of HEV from pigs to exposed workers and from pork or organs to consumption.

4.
Front Plant Sci ; 15: 1419508, 2024.
Article de Anglais | MEDLINE | ID: mdl-38933465

RÉSUMÉ

Brassica napus is one of the most important oil crops in the world. Breeding oilseed rape with colorful flowers can greatly enhance the ornamental value of B. napus and thus improve the economic benefits of planting. As water-soluble flavonoid secondary metabolites, anthocyanins are very important for the synthesis and accumulation of pigments in the petals of plants, giving them a wide range of bright colors. Despite the documentation of over 60 distinct flower shades in B. napus, the intricacies underlying flower color variation remain elusive. Particularly, the mechanisms driving color development across varying flower color backgrounds necessitate further comprehensive investigation. This research undertook a comprehensive exploration through the integration of transcriptome and metabolome analyses to pinpoint pivotal genes and metabolites underpinning an array of flower colors, including beige, beige-red, yellow, orange-red, deep orange-red, white, light-purple, and purple. First, we used a two-way BLAST search to find 275 genes in the reference genome of B. napus Darmor v10 that were involved in making anthocyanins. The subsequent scrutiny of RNA-seq outcomes underscored notable upregulation in the structural genes F3H and UGT, alongside the MYB75, GL3, and TTG1 transcriptional regulators within petals, showing anthocyanin accumulation. By synergizing this data with a weighted gene co-expression network analysis, we identified CHS, F3H, MYB75, MYB12, and MYB111 as the key players driving anthocyanin synthesis in beige-red, orange-red, deep orange-red, light-purple, and purple petals. By integrating transcriptome and weighted gene co-expression network analysis findings with anthocyanin metabolism data, it is hypothesized that the upregulation of MYB75, which, in turn, enhances F3H expression, plays a pivotal role in the development of pigmented oilseed rape flowers. These findings help to understand the transcriptional regulation of anthocyanin biosynthesis in B. napus and provide valuable genetic resources for breeding B. napus varieties with novel flower colors.

5.
BMC Genomics ; 25(1): 624, 2024 Jun 20.
Article de Anglais | MEDLINE | ID: mdl-38902601

RÉSUMÉ

Radish exhibits significant variation in color, particularly in sprouts, leaves, petals, fleshy roots, and other tissues, displaying a range of hues such as green, white, red, purple, and black. Although extensive research has been conducted on the color variation of radish, the underlying mechanism behind the variation in radish flower color remains unclear. To date, there is a lack of comprehensive research investigating the variation mechanism of radish sprouts, leaves, fleshy roots, and flower organs. This study aims to address this gap by utilizing transcriptome sequencing to acquire transcriptome data for white and purple radish flowers. Additionally, the published transcriptome data of sprouts, leaves, and fleshy roots were incorporated to conduct a systematic analysis of the regulatory mechanisms underlying anthocyanin biosynthesis in these four radish tissues. The comparative transcriptome analysis revealed differential expression of the anthocyanin biosynthetic pathway genes DFR, UGT78D2, TT12 and CPC in the four radish tissues. Additionally, the WGCNA results identified RsDFR.9c and RsUGT78D2.2c as hub genes responsible for regulating anthocyanin biosynthesis. By integrating the findings from the comparative transcriptome analysis, WGCNA, and anthocyanin biosynthetic pathway-related gene expression patterns, it is hypothesized that genes RsDFR.9c and RsUGT78D2.2c may serve as pivotal regulators of anthocyanins in the four radish tissues. Furthermore, the tissue-specific expression of the four copies of RsPAP1 is deemed crucial in governing anthocyanin synthesis and accumulation. Our results provide new insights into the molecular mechanism of anthocyanin biosynthesis and accumulation in different tissues of radish.


Sujet(s)
Anthocyanes , Analyse de profil d'expression de gènes , Régulation de l'expression des gènes végétaux , Raphanus , Raphanus/génétique , Raphanus/métabolisme , Anthocyanes/biosynthèse , Anthocyanes/génétique , Transcriptome , Voies de biosynthèse/génétique , Protéines végétales/génétique , Protéines végétales/métabolisme , Fleurs/génétique , Fleurs/métabolisme
6.
J Headache Pain ; 25(1): 94, 2024 Jun 05.
Article de Anglais | MEDLINE | ID: mdl-38840241

RÉSUMÉ

BACKGROUND: Migraine is a common neurological disorder with a strong genetic component. Despite the identification of over 100 loci associated with migraine susceptibility through genome-wide association studies (GWAS), the underlying causative genes and biological mechanisms remain predominantly elusive. METHODS: The FinnGen R10 dataset, consisting of 333,711 subjects (20,908 cases and 312,803 controls), was utilized in conjunction with the Genotype-Tissue Expression Project (GTEx) v8 EQTls files to conduct cross-tissue transcriptome association studies (TWAS). Functional Summary-based Imputation (FUSION) was employed to validate these findings in single tissues. Additionally, candidate susceptibility genes were screened using Gene Analysis combined with Multi-marker Analysis of Genomic Annotation (MAGMA). Subsequent Mendelian randomization (MR) and colocalization analyses were conducted. Furthermore, GeneMANIA analysis was employed to enhance our understanding of the functional implications of these susceptibility genes. RESULTS: We identified a total of 19 susceptibility genes associated with migraine in the cross-tissue TWAS analysis. Two novel susceptibility genes, REV1 and SREBF2, were validated through both single tissue TWAS and MAGMA analysis. Mendelian randomization and colocalization analyses further confirmed these findings. REV1 may reduce the migraine risk by regulating DNA damage repair, while SREBF2 may increase the risk of migraine by regulating cholesterol metabolism. CONCLUSION: Our study identified two novel genes whose predicted expression was associated with the risk of migraine, providing new insights into the genetic framework of migraine.


Sujet(s)
Prédisposition génétique à une maladie , Étude d'association pangénomique , Migraines , Transcriptome , Humains , Migraines/génétique , Prédisposition génétique à une maladie/génétique , Transcriptome/génétique , Analyse de randomisation mendélienne , Polymorphisme de nucléotide simple/génétique
7.
Food Res Int ; 188: 114393, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38823852

RÉSUMÉ

After successfully addressing to mitigate bitterness of naringin through construction Pickering emulsion using pea protein (PP) and naringin (NG) in our previous study, we now probed thermal stability, antioxidant efficacy, and bioavailability. FTIR analysis and UV-vis spectroscopy indicated predominant interactions between PP and NG were hydrogen and hydrophobic bonds. TGA and DSC analyses demonstrated that PP-NG complexes exhibited superior heat-resistance compared to pure PP and NG. Thermal stability assessments indicated a significant retention of NG in the PP-NG Pickering emulsion than the control NG across varied temperatures (4 °C, 25 °C, 37 °C, and 65 °C). Moreover, the antioxidant activity of PP-NG emulsion was dependent on the concentration of NG, as evidenced by DPPH and ABTS free radicals scavenging abilities, ferric reducing power, and lipid peroxidation resistance. Additionally, PP-NG Pickering emulsion exhibited substantially high bioavailability (92.01 ± 3.91%). These results suggest a promising avenue for the application of NG with improved characteristics.


Sujet(s)
Antioxydants , Biodisponibilité , Émulsions , Flavanones , Protéines de pois , Flavanones/composition chimique , Antioxydants/composition chimique , Protéines de pois/composition chimique , Température élevée , Spectroscopie infrarouge à transformée de Fourier , Peroxydation lipidique/effets des médicaments et des substances chimiques , Pisum sativum/composition chimique
8.
Mol Neurobiol ; 2024 Jun 19.
Article de Anglais | MEDLINE | ID: mdl-38896157

RÉSUMÉ

The blood-brain barrier (BBB) is a complex structure that separates the central nervous system (CNS) from the peripheral blood circulation. Effective communication between different cell types within the BBB is crucial for its proper functioning and maintenance of homeostasis. In this study, we demonstrate that meningitic Escherichia coli (E. coli)-induced WNT5B plays a role in facilitating intercellular communication between astrocytes and brain microvascular endothelial cells (BMECs). We discovered that astrocytes-derived WNT5B activates the non-canonical WNT signaling pathway JNK/c-JUN in BMECs through its receptor ROR1, leading to inhibition of ZO-1 expression and impairment of the tight junction integrity in BMECs. Notably, our findings reveal that c-JUN, a transcription factor, directly regulates ZO-1 expression. By employing a dual luciferase reporting system and chromatin immunoprecipitation techniques, we identified specific binding sites of c-JUN on the ZO-1 promoter region. Overall, our study highlights the involvement of WNT5B in mediating intercellular communication between astrocytes and BMECs, provides insights into the role of WNT5B in meningitic E. coli-induced disruption of BBB integrity, and suggests potential therapeutic targeting of WNT5B as a strategy to address BBB dysfunction.

9.
Int J Biol Macromol ; 271(Pt 2): 132623, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38845255

RÉSUMÉ

Shellac is a natural resin featuring some attractive properties such as amphiphilicity, pH responsiveness, biocompatibility, and biodegradability. There has been increasing interest in employing shellac for controlled delivery of food bioactive compounds. This review outlines the recent advances in different types of shellac-based delivery systems, including nanoparticles, zein-shellac particles, hydrogels, nanofibers, and nanomicelles. The preparation method, formation mechanism, structure, and delivery performance are investigated. These systems could improve the stability and shelf-life of bioactive compounds, allow for targeted release at the small intestine or colon site, and increase bioavailability. The deficiencies and challenges of each of the systems are also discussed. The promising results in this review could guide future trends in more efficient shellac-based delivery platforms for functional food applications.


Sujet(s)
Résines végétales , Humains , Résines végétales/composition chimique , Systèmes de délivrance de médicaments , Zéine/composition chimique , Nanoparticules/composition chimique , Hydrogels/composition chimique , Nanofibres/composition chimique , Animaux , Biodisponibilité
10.
Article de Anglais | MEDLINE | ID: mdl-38833098

RÉSUMÉ

BACKGROUND: Catheter ablation of parahisian accessory pathways (PHAP) are challenging due to their proximity to the normal conduction system. Retrospective studies suggest that cryoablation has a better safety profile but a higher recurrence rate when compared to radiofrequency ablation (RFCA). The objective of this study was to compare the results of parahisian AP ablation performed by electrophysiologists with experience in both technologies. METHODS: Prospective single-center, non-blinded and 1:1 model was used. Patients included had parahisian AP confirmed by an electrophysiological study and referred for radiofrequency or cryotherapy ablation according to current guidelines, under fluoroscopic guidance. No electroanatomic mapping was used. RESULTS: A total of 30 patients (mean age of 25±9.4 years; 90% male) were enrolled between Oct/2018 to Feb/2020. Acute success rate between RFCA and CRYO were similar (93% vs. 87%, p = 0.54). A nonsignificant reduction in short-term recurrence rate for RFCA (14% vs. 30%, p = 0.3) and mechanical trauma (6% vs. 20%; p = 0.28) was observed. Long-term recurrence rate and event-free survival time were similar in both groups after 1-year follow-up (p = 0.286). No persistent complete AV block or conduction disturbance was also observed. CONCLUSION: Considering the limitation of a small sample size and the lack of use of electroanatomic mapping for RFCA, the efficacy and safety profile of parahisian AP ablation with RFCA was not different from CRYO, when performed by experienced electrophysiologists. No cases of permanent complete AV block were reported with either energy modalities.

11.
Adv Colloid Interface Sci ; 328: 103174, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38728772

RÉSUMÉ

The most common carrier for encapsulation of bioactive components is still simple emulsion. Recently, bio-based novel emulsion systems such as multiple emulsions (MEs) and Pickering emulsions (PEs) have been introduced as innovative colloidal delivery systems for encapsulation and controlled release of bioactive compounds. Multiple PEs (MPEs), which carries both benefit of MEs and PEs could be fabricated by relatively scalable and simple operations. In comparison with costly synthetic surfactants and inorganic particles which are widely used for stabilization of both MEs and PEs, MPEs stabilized by food-grade particles, while having health-promoting aspects, are able to host the "clean label" and "green label" attributes. Nevertheless, in achieving qualified techno-functional attributes and encapsulation properties, the selection of suitable materials is a crucial step in the construction of such complex systems. Current review takes a cue from both MEs and PEs emulsification techniques to grant a robust background for designing various MPEs. Herein, various fabrication methods of MEs and PEs are described comprehensively in a physical viewpoint in order to find key conception of successful formulation of MPEs. This review also highlights the link between the underlying aspects and exemplified specimens of evidence which grant insights into the rational design of MPEs through food-based ingredients to introduces MPEs as novel colloidal/functional materials. Their utilization for encapsulation of bioactive compounds is discussed as well. In the last part, instability behavior of MPEs under various conditions will be discussed. In sum, this review aims to gain researchers who work with food-based components, basics of innovative design of MPEs.


Sujet(s)
Émulsions , Émulsions/composition chimique , Systèmes de délivrance de médicaments , Humains , Taille de particule , Tensioactifs/composition chimique
12.
J Virol ; 98(6): e0046124, 2024 Jun 13.
Article de Anglais | MEDLINE | ID: mdl-38780247

RÉSUMÉ

Transmissible gastroenteritis virus (TGEV)-induced enteritis is characterized by watery diarrhea, vomiting, and dehydration, and has high mortality in newborn piglets, resulting in significant economic losses in the pig industry worldwide. Conventional cell lines have been used for many years to investigate inflammation induced by TGEV, but these cell lines may not mimic the actual intestinal environment, making it difficult to obtain accurate results. In this study, apical-out porcine intestinal organoids were employed to study TEGV-induced inflammation. We found that apical-out organoids were susceptible to TGEV infection, and the expression of representative inflammatory cytokines was significantly upregulated upon TGEV infection. In addition, retinoic acid-inducible gene I (RIG-I) and the nuclear factor-kappa B (NF-κB) pathway were responsible for the expression of inflammatory cytokines induced by TGEV infection. We also discovered that the transcription factor hypoxia-inducible factor-1α (HIF-1α) positively regulated TGEV-induced inflammation by activating glycolysis in apical-out organoids, and pig experiments identified the same molecular mechanism as the ex vivo results. Collectively, we unveiled that the inflammatory responses induced by TGEV were modulated via the RIG-I/NF-κB/HIF-1α/glycolysis axis ex vivo and in vivo. This study provides novel insights into TGEV-induced enteritis and verifies intestinal organoids as a reliable model for investigating virus-induced inflammation. IMPORTANCE: Intestinal organoids are a newly developed culture system for investigating immune responses to virus infection. This culture model better represents the physiological environment compared with well-established cell lines. In this study, we discovered that inflammatory responses induced by TGEV infection were regulated by the RIG-I/NF-κB/HIF-1α/glycolysis axis in apical-out porcine organoids and in pigs. Our findings contribute to understanding the mechanism of intestinal inflammation upon viral infection and highlight apical-out organoids as a physiological model to mimic virus-induced inflammation.


Sujet(s)
Gastroentérite transmissible du porc , Glycolyse , Inflammation , Organoïdes , Virus de la gastroentérite transmissible , Animaux , Cytokines/métabolisme , Protéine-58 à domaine DEAD/métabolisme , Protéine-58 à domaine DEAD/génétique , Gastroentérite transmissible du porc/virologie , Gastroentérite transmissible du porc/métabolisme , Gastroentérite transmissible du porc/anatomopathologie , Sous-unité alpha du facteur-1 induit par l'hypoxie/métabolisme , Sous-unité alpha du facteur-1 induit par l'hypoxie/génétique , Inflammation/métabolisme , Inflammation/virologie , Intestins/virologie , Intestins/anatomopathologie , Facteur de transcription NF-kappa B/métabolisme , Organoïdes/virologie , Organoïdes/métabolisme , Organoïdes/anatomopathologie , Transduction du signal , Suidae , Virus de la gastroentérite transmissible/physiologie
14.
ACS Infect Dis ; 10(5): 1576-1589, 2024 05 10.
Article de Anglais | MEDLINE | ID: mdl-38581387

RÉSUMÉ

Exploring novel antimicrobial drugs and strategies has become essential to the fight MRSA-associated infections. Herein, we found that membrane-disrupted repurposed antibiotic salifungin had excellent bactericidal activity against MRSA, with limited development of drug resistance. Furthermore, adding salifungin effectively decreased the minimum inhibitory concentrations of clinical antibiotics against Staphylococcus aureus. Evaluations of the mechanism demonstrated that salifungin disrupted the level of H+ and K+ ions using hydrophilic and lipophilic groups to interact with bacterial membranes, causing the disruption of bacterial proton motive force followed by impacting on bacterial the function of the respiratory chain and adenosine 5'-triphosphate, thereby inhibiting phosphatidic acid biosynthesis. Moreover, salifungin also significantly inhibited the formation of bacterial biofilms and eliminated established bacterial biofilms by interfering with bacterial membrane potential and inhibiting biofilm-associated gene expression, which was even better than clinical antibiotics. Finally, salifungin exhibited efficacy comparable to or even better than that of vancomycin in the MRSA-infected animal models. In conclusion, these results indicate that salifungin can be a potential drug for treating MRSA-associated infections.


Sujet(s)
Antibactériens , Biofilms , Repositionnement des médicaments , Staphylococcus aureus résistant à la méticilline , Tests de sensibilité microbienne , Infections à staphylocoques , Staphylococcus aureus résistant à la méticilline/effets des médicaments et des substances chimiques , Antibactériens/pharmacologie , Biofilms/effets des médicaments et des substances chimiques , Infections à staphylocoques/traitement médicamenteux , Infections à staphylocoques/microbiologie , Animaux , Souris , Résistance bactérienne aux médicaments/effets des médicaments et des substances chimiques
15.
J Assist Reprod Genet ; 41(6): 1485-1498, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38568462

RÉSUMÉ

PURPOSE: This study aimed to identify the genetic causes of male infertility and primary ciliary dyskinesia (PCD)/PCD-like phenotypes in three unrelated Han Chinese families. METHODS: We conducted whole-exome sequencing of three patients with male infertility and PCD/PCD-like phenotypes from three unrelated Chinese families. Ultrastructural and immunostaining analyses of patient spermatozoa and respiratory cilia and in vitro analyses were performed to analyze the effects of SPEF2 variants. Intracytoplasmic sperm injection (ICSI) was administered to three affected patients. RESULTS: We identified four novel SPEF2 variants, including one novel homozygous splicing site variant [NC_000005.10(NM_024867.4): c.4447 + 1G > A] of the SPEF2 gene in family 1, novel compound heterozygous nonsense variants [NC_000005.10(NM_024867.4): c.1339C > T (p.R447*) and NC_000005.10(NM_024867.4): c.1645G > T (p.E549*)] in family 2, and one novel homozygous missense variant [NC_000005.10(NM_024867.4): c.2524G > A (p.D842N)] in family 3. All the patients presented with male infertility and PCD/likely PCD. All variants were present at very low levels in public databases, predicted to be deleterious in silico prediction tools, and were further confirmed deleterious by in vitro analyses. Ultrastructural analyses of the spermatozoa of the patients revealed the absence of the central pair complex in the sperm flagella. Immunostaining of the spermatozoa and respiratory cilia of the patients validated the pathogenicity of the SPEF2 variants. All patients carrying SPEF2 variants underwent one ICSI cycle and delivered healthy infants. CONCLUSION: Our study reported four novel pathogenic variants of SPEF2 in three male patients with infertility and PCD/PCD-like phenotypes, which not only extend the spectrum of SPEF2 mutations but also provide information for genetic counseling and treatment of such conditions.


Sujet(s)
Infertilité masculine , Pedigree , Injections intracytoplasmiques de spermatozoïdes , Spermatozoïdes , Humains , Mâle , Infertilité masculine/génétique , Infertilité masculine/anatomopathologie , Adulte , Spermatozoïdes/anatomopathologie , Spermatozoïdes/ultrastructure , Spermatozoïdes/métabolisme , , Troubles de la motilité ciliaire/génétique , Troubles de la motilité ciliaire/anatomopathologie , Phénotype , Cils vibratiles/génétique , Cils vibratiles/anatomopathologie , Cils vibratiles/ultrastructure , Mutation/génétique , Chine , Homozygote
16.
Breast Cancer Res Treat ; 206(1): 45-56, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38616207

RÉSUMÉ

PURPOSE: The significance of postmastectomy radiotherapy (PMRT) in breast cancer patients who initially have clinically node-positive (cN +) status but achieve downstaging to ypN0 following neoadjuvant chemotherapy (NAC) remains uncertain. This study aims to assess the impact of PMRT in this patient subset. METHODS: Patients were enrolled from West China Hospital, Sichuan University from 2008 to 2019. Overall survival (OS), Locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and breast cancer-specific survival (BCSS) were estimated using the Kaplan-Meier method and assessed with the log-rank test. The impact of PMRT was further analyzed by the Cox proportional hazards model. Propensity score matching (PSM) was performed to reduce the selection bias. RESULTS: Of the 333 eligible patients, 189 (56.8%) received PMRT, and 144 (43.2%) did not. At a median follow-up period of 71 months, the five-year LRFS, DMFS, BCSS, and OS rates were 99.1%, 93.4%, 96.4%, and 94.3% for the entire cohort, respectively. Additionally, the 5-year LRFS, DMFS, BCSS, and OS rates were 98.9%, 93.8%, 96.7%, and 94.5% with PMRT and 99.2%, 91.3%, 94.9%, and 92.0% without PMRT, respectively (all p-values not statistically significant). After multivariate analysis, PMRT was not a significant risk factor for any of the endpoints. When further stratified by stage, PMRT did not show any survival benefit for patients with stage II-III diseases. CONCLUSION: In the context of comprehensive treatments, PMRT might be exempted in ypN0 breast cancer patients. Further large-scale, randomized controlled studies are required to investigate the significance of PMRT in this patient subset.


Sujet(s)
Tumeurs du sein , Mastectomie , Traitement néoadjuvant , Stadification tumorale , Humains , Femelle , Tumeurs du sein/anatomopathologie , Tumeurs du sein/thérapie , Tumeurs du sein/mortalité , Tumeurs du sein/traitement médicamenteux , Tumeurs du sein/radiothérapie , Adulte d'âge moyen , Traitement néoadjuvant/méthodes , Adulte , Sujet âgé , Études rétrospectives , Radiothérapie adjuvante/méthodes , Traitement médicamenteux adjuvant/méthodes , Métastase lymphatique , Récidive tumorale locale/anatomopathologie
17.
Food Res Int ; 184: 114228, 2024 May.
Article de Anglais | MEDLINE | ID: mdl-38609215

RÉSUMÉ

There is a growing interest in employing whole food-based strategies to prevent chronic diseases, owing to the potential synergistic interactions among various bioactive components found within whole foods. The current research aimed to determine inhibitory effects of the whole edible mushroom Pleurotus eryngii (WPE) on high-fat diet (HFD)-induced obesity in mice. Our results showed that dietary intake of WPE significantly inhibited the abnormal gain of body weight and adipose tissue weight, improved glucose tolerance, and ameliorated the serum biochemical parameters in HFD-fed mice. The histological analysis illustrated that the severity of non-alcoholic fatty liver induced by HFD was significantly reduced by WPE. Oral intake of WPE profoundly modulated the mRNA levels of hepatic genes involved in lipid metabolism and also increased the level of short-chain fatty acids in the mouse cecum. Moreover, WPE alleviated the HFD-induced gut microbiota dysbiosis, increasing the abundance of beneficial bacteria (Akkermansia, Lactobacillus, Bifidobacterium, and Sutteralla), and decreasing the harmful ones (rc4-4, Dorea, Coprococcus, Oscillospira, and Ruminococcus). These findings presented new evidence supporting that WPE could be used as a whole food-based strategy to protect against obesity and obesity-driven health problems.


Sujet(s)
Microbiome gastro-intestinal , Pleurotus , Animaux , Souris , Dysbiose , Métabolisme lipidique , Obésité/prévention et contrôle , Consommation alimentaire
18.
Research (Wash D C) ; 7: 0343, 2024.
Article de Anglais | MEDLINE | ID: mdl-38550777

RÉSUMÉ

Fut2-mediated α1,2-fucosylation is important for gut homeostasis, including the intestinal stem cell (ISC). The stemness of ISC declines with age, and aging-associated ISC dysfunction is closely related to many age-related intestinal diseases. We previously found intestinal epithelial dysfunction in some aged Fut2 knockout mice. However, how Fut2-mediated α1,2-fucosylation affects ISC aging is still unknown. On this basis, the herein study aims to investigate the role of Fut2-mediated α1,2-fucosylation in ISC aging. Aging models in ISC-specific Fut2 knockout mice were established. ISCs were isolated for proteomics and N-glycoproteomics analysis. ISC functions and mitochondrial functions were examined in mice and organoids. Ulex europaeus agglutinin I chromatography and site-directed mutagenesis were used to validate the key target fucosylated proteins of Fut2. As a result, Fut2 knockout impaired ISC stemness and promoted aging marker expression in aged mice. Proteomics analysis indicated mitochondrial dysfunction in Fut2 knockout ISC. More injured mitochondria, elevated levels of reactive oxygen species, and decreased levels of adenosine 5'-triphosphate (ATP) in Fut2 knockout ISC were found. Moreover, respiratory chain complex impairment and mitophagy dysfunction in Fut2 knockout ISC were further noted. Finally, Fut2 was demonstrated to regulate mitochondrial functions mainly by regulating the α1,2-fucosylation of N-acyl sphingosine amidohydrolase 2 (Asah2) and Niemann-Pick type C intracellular cholesterol transporter 1 (Npc1). In conclusion, this study demonstrated the substantial role of Fut2 in regulating ISC functions during aging by affecting mitochondrial function. These findings provide novel insights into the molecular mechanisms of ISC aging and therapeutic strategies for age-related intestinal diseases.

19.
Front Microbiol ; 15: 1357579, 2024.
Article de Anglais | MEDLINE | ID: mdl-38529180

RÉSUMÉ

Potato early blight (PEB), a foliar disease of potato during the growing period, caused by Alternaria sp., is common in major potato-producing areas worldwide. Effective agents to control this disease or completely resistant potato varieties are absent. Large-scale use of fungicides is limited due to possibility of increase in pathogen resistance and the requirements of ecological agriculture. In this study, we focused on the composition and infection characteristics of early blight pathogens in Yunnan Province and screened candidate pathogenesis-related pathways and genes. We isolated 85 strains of Alternaria sp. fungi from typical early blight spots in three potato-growing regions in Yunnan Province from 2018 to 2022, and identified 35 strains of Alternaria solani and 50 strains of Alternaria alternata by morphological characterization and ITS sequence comparison, which were identified as the main and conditional pathogens causing early blight in potato, respectively. Scanning electron microscope analysis confirmed only A. solani producing appressorium at 4 h after inoculation successfully infected the leaf cells. Via genome assembly and annotation, combine transcriptome and proteomic analysis, the following pathogenicity-related unit, transcription factors and metabolic pathway were identified: (1) cell wall-degrading enzymes, such as pectinase, keratinase, and cellulase; (2) genes and pathways related to conidia germination and pathogenicity, such as ubiquitination and peroxisomes; and (3) transcription factors, such as Zn-clus, C2H2, bZIP, and bHLH. These elements were responsible for PEB epidemic in Yunnan.

20.
J Am Chem Soc ; 146(10): 6837-6845, 2024 Mar 13.
Article de Anglais | MEDLINE | ID: mdl-38426800

RÉSUMÉ

The efficient synthesis of polar-functionalized polypropylenes with high molecular weight and high stereoregularity represents a challenging task. This challenge becomes even more daunting when pursuing an industrially preferred heterogeneous process. This study demonstrated the realization of these goals through the use of commercial heterogeneous Ziegler-Natta catalysts in the copolymerization of propylene with ionic cluster polar monomers. The results revealed high copolymerization activity (∼1.1 × 107 g mol-1 h-1), moderate polar monomer incorporation ratios (∼4.9 mol %), high copolymer molecular weight (Mw > 105 g mol-1), high stereoregularity ([mmmm] ∼ 96%), and high melting temperature range (150-162 °C). The utilization of ionic cluster polar monomers improved the thermal stability as well as stereoselectivity of the catalyst. Moreover, the Ziegler-Natta catalyst can homopolymerize ionic cluster polar monomers with high activities (>104 g mol-1 h-1). The resulting polar-functionalized isotactic polypropylenes (iPP) exhibited superior tensile strength, impact strength, creep resistance, transparency, and crystallinity compared with nonpolar iPP. This enhancement was attributable to the dual roles of the ionic cluster polar monomer unit, serving as both a transparent nucleating agent and a dynamic cross-linking functionality. Furthermore, the polar-functionalized iPP exhibited improved compatibility with polar materials, offering benefits for applications in composites, recycling of mixed plastic wastes, 3D printing, and other fields. This study offered a comprehensive solution for the future industrial production of polar-functionalized iPP via copolymerization, bridging the gap between an efficient and practical copolymerization process from a synthetic chemistry perspective and enhanced material properties from an application perspective.

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