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1.
Cell Death Discov ; 10(1): 431, 2024 Oct 09.
Article in English | MEDLINE | ID: mdl-39384750

ABSTRACT

Persistent macrophage activation and cytokine storms are critical causes for the rapid disease progression and high mortality rate of Secondary Hemophagocytic lymphohistiocytosis (sHLH). Identification of key regulatory factors that govern the activation of macrophages is vital. Plasma exosomal circular RNAs (circRNAs) are considered important biomarkers and potential therapeutic targets for various diseases, however, their function in sHLH is still unclear. In this study, we demonstrated for the first time that circMETTL3, derived from METTL3, is upregulated in sHLH patient plasma exosomes, which may plays an important role in the diagnosis of sHLH. Significantly, we also revealed that a novel peptide encoded by circMETTL3, METTL3-156aa, is an inducer of M1 macrophage polarization, which is responsible for the development of cytokine storms during sHLH. We then identified that METTL3-156aa binding with lactate dehydrogenase A (LDHA) and promotes M1 macrophage polarization by enhancing macrophage glycolysis. Additionally, the glycolysis metabolite lactate upregulates the cleavage factor SRSF10 expression by lactylation. This results in increased splicing of the pre-METTL3 mRNA, leading to an enchance in the production of cirMETTL3. Therefore, our results suggest that the circMETTL3/METTL3-156aa/LDHA/Lactate/SRSF10 axis forms a positive feedback loop and may be a novel therapeutic target for the treatment of sHLH.

2.
J Neurointerv Surg ; 2024 Oct 08.
Article in English | MEDLINE | ID: mdl-39379315

ABSTRACT

BACKGROUND: Accurately forecasting early neurological deterioration of ischemic origin (ENDi) following medical management may aid in identifying candidates for thrombectomy. We aimed to develop and validate a nomogram to predict ENDi in patients with mild large and medium vessel occlusion stroke intended for medical management. METHODS: Two hundred and forty-eight patients were enrolled (173 and 75 randomised into training and validation cohorts). The risk factors were identified using logistic regression analyses. A nomogram was constructed based on the risk factors identified. The discrimination, calibration, and clinical practicability of the nomogram were assessed using receiver operating characteristic curve (ROC) analysis, the Hosmer-Lemeshow test, and decision curve analysis (DCA), respectively. RESULTS: ENDi was detected in 44 (17.7%) patients. Four predictors were identified in the training cohort and entered into the nomogram including age, symptom fluctuation characteristics, presence of core infarct, and occlusion site. ROC analysis showed that the area under the curve was 0.930 (95% CI 0.884 to 0.976) and 0.889 (95% CI 0.808 to 0.970) in the training and validation cohorts, respectively. The Hosmer-Lemeshow test yielded a mean absolute error of 0.025 and 0.038, respectively, for the two cohorts. The DCA showed that the nomogram model had superior practicality and accuracy across the majority of the threshold probabilities. CONCLUSION: The proposed nomogram showed a favourable predictive performance for ENDi in patients with mild large and medium vessel occlusion stroke intended for medical management. For such patients, immediate thrombectomy or at least intensive medical monitoring may be reasonable to avoid delays in rescue thrombectomy.

3.
Commun Biol ; 7(1): 1254, 2024 Oct 03.
Article in English | MEDLINE | ID: mdl-39363116

ABSTRACT

Congenital heart defects are leading causes of neonatal mortality and are often associated with placental abnormalities, but mechanisms linking placenta and heart development are poorly understood. Herein, we investigated a potential signaling network connecting the placenta and nascent heart in mice. We found that fetal hearts exposed to media conditioned by placental tissue or differentiated wild-type trophoblast stem (TS) cells, but not undifferentiated TS cells, showed increased heart rate and epicardial cell outgrowth. This effect was not observed when hearts were exposed to media from TS cells lacking OVO-Like 2, a transcription factor required for trophoblast differentiation and placental development. Trophoblasts released abundant extracellular vesicles into media, and these vesicles were sufficient to mediate cardio-promoting effects. Our findings provide a potential mechanism whereby the placenta communicates with the fetal heart to promote cardiac morphogenesis, and offers insight into the link between poor placentation and a higher incidence of heart defects.


Subject(s)
Extracellular Vesicles , Myocytes, Cardiac , Placenta , Animals , Extracellular Vesicles/metabolism , Female , Pregnancy , Myocytes, Cardiac/metabolism , Mice , Placenta/metabolism , Fetal Heart/metabolism , Fetal Heart/embryology , Cell Differentiation , Trophoblasts/metabolism , Mice, Inbred C57BL
4.
Phys Chem Chem Phys ; 26(37): 24667-24675, 2024 Sep 25.
Article in English | MEDLINE | ID: mdl-39279742

ABSTRACT

The BiFeO3-BaTiO3 solid solution exhibits enhanced electric properties due to its modified phase structure with relaxor characteristics and reduced leakage current. Despite these advancements, the underlying mechanism behind the phase transition from a ferroelectric to a relaxor state in BF-BT ceramics remains largely unexplored. Here, the evolution of strain in (0.67 - x)BiFeO3-0.33BaTiO3-xBi(Mg0.5Zr0.5)O3 ceramics is investigated, with a focus on the strain transition from a ferroelectric to a relaxor phase. A strengthening of relaxor behavior is observed in the modified rhombohedral (R) and pseudocubic (PC) phase structure, resulting in optimal strain (Suni = 0.25%, Spos = 0.24%) at x = 0.04. The enhanced strain is attributed to the promotion of domain switching and the presence of strong random fields, with polar nanoregions integrating into a long-range ordered matrix. Furthermore, a gradual increase in strain with rising temperature is noted, driven by increased polarization and the expansion of ferroelectric domains. This study underscores the critical role of structural modifications in augmenting the electric response of BF-BT ceramics, thereby advancing the development of lead-free piezoelectric materials.

5.
Mikrochim Acta ; 191(10): 635, 2024 09 30.
Article in English | MEDLINE | ID: mdl-39347992

ABSTRACT

The 3-phenoxybenzoic acid (3-PBA) residues in environment are posing a significant challenge to our daily lives. To establish a more sensitive and rapid detection method, anti-3-PBA nanobodies (Nbs) were immobilized onto magnetosomes (bacterial magnetic nanoparticles, termed as BMPs), forming a robust BMP-Nb complex. The 3-PBA derivative was labeled with horseradish peroxidase (HRP) and further associated with gold nanoparticles (AuNPs) to create a highly sensitive probe (3-PBA-HRP-AuNP). An innovative immunoassay that combined BMP-Nb complex with 3-PBA-HRP-AuNP was developed for determinaton of 3-PBA. This method enabled the determination of 3-PBA with a half-maximum signal inhibition concentration (IC50) of 1.03 ng/mL, which was more sensitive than that of using 3-PBA-HRP as tracer with an IC50 of 2.18 ng/mL. The reliability of the assay was evidenced by the quantitative recovery of 3-PBA from water and soil samples ranging from 76.85 to 95.64%. The 3-PBA residues determined by this assay in actual water samples were between < LOD and 2.54 ng/mL and were between < LOD and 11.25 ng/g (dw) in real soils, respectively, which agreed well with those of liquid chromatography mass spectrometry (LC-MS). Collectively, the BMP-Nb and 3-PBA-HRP-AuNP-based immunoassay provides a powerful tool for the precise detection of 3-PBA residues in environment matrices, reinforcing our capacity to monitor and mitigate potential ecological and health impacts associated with this prevalent pollutant.


Subject(s)
Benzoates , Gold , Metal Nanoparticles , Gold/chemistry , Metal Nanoparticles/chemistry , Benzoates/chemistry , Single-Domain Antibodies/chemistry , Single-Domain Antibodies/immunology , Limit of Detection , Immunoassay/methods , Horseradish Peroxidase/chemistry , Immunomagnetic Separation/methods , Antibodies, Immobilized/immunology , Water Pollutants, Chemical/analysis
6.
J Int Med Res ; 52(9): 3000605241272609, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39246065

ABSTRACT

The glomus tumor is a rare neoplasm that is typically found subungually in the extremities and functions as a specialized neurovascular organ. An extremely rare site for glomus tumors is the breast, with only a few reported cases. Breast glomus tumors present with three typical clinical signs: dull pain, focal tenderness, and cold sensitivity. Less than 10% of all glomus tumors are malignant. We herein present a case of a malignant glomus tumor originating in the breast. Distant metastasis was ruled out, and the tumor was completely resected. However, the patient unexpectedly developed rapid systemic metastasis, detected 5 weeks after tumor removal. Despite the administration of analgesics and targeted therapy, the patient died 1 month later. When treating patients with undiagnosed breast tumors, clinicians should pay attention to unexplained and repeatedly reported symptoms and consider the possibility of a rare disease. Our literature search revealed no cases of malignant glomus tumors originating in the breast, making this case the first of its kind.


Subject(s)
Breast Neoplasms , Glomus Tumor , Humans , Glomus Tumor/pathology , Glomus Tumor/diagnosis , Glomus Tumor/surgery , Female , Breast Neoplasms/pathology , Breast Neoplasms/surgery , Breast Neoplasms/diagnosis , Middle Aged , Fatal Outcome , Disease Progression
7.
ACS Appl Mater Interfaces ; 16(40): 54548-54554, 2024 Oct 09.
Article in English | MEDLINE | ID: mdl-39327069

ABSTRACT

In human life and production, excessive oily wastewaters containing detergents are produced and discharged, causing severe environmental pollution and water resource problems. A metal-organic framework (MOF)-based membrane is an economical and environmentally friendly tool for emulsion separation but is limited by a complex preparation process and poor flexibility. Herein, we developed a simple method to synthesize a MOF-based mixed-matrix membrane (MMM) by spray and fabricated the membrane on poly(vinylidene fluoride) (PVDF) fibers via postdeposition and in situ growth manners. The prepared ZIF-8/PVA MMMs have uniform distribution of ZIF-8 particles and poly(vinyl alcohol) (PVA) on the PVDF fibers. PVA improved the adhesion between the ZIF-8 particles and between the MOF layer and PVDF fiber, endowing the separation membrane with high flexibility and bendability. The prepared ZIF-8/PVA membrane exhibited hydrophilicity and underwater superoleophobicity, which showed high separation efficiency and considerable water flux for emulsions, emulsion containing dye, and surfactant-stabilized emulsion. In addition, the fabricated ZIF-8/PVA/PVDF fibers exhibited good antifouling property and flexibility and can maintain stable separation efficiency after working several times and even under bending, demonstrating the stability and potentiality of the ZIF-8/PVA/PVDF fibers in practical applications. This work paves a new avenue for the synthesis and application of MOF-based MMMs.

8.
Int Immunopharmacol ; 142(Pt A): 113072, 2024 Dec 05.
Article in English | MEDLINE | ID: mdl-39241514

ABSTRACT

BACKGROUND: Aberrant differentiation of Th17 cells has been identified as a critical factor in the development of rheumatoid arthritis (RA). BLIMP1 plays a key role in regulating plasma cell differentiation, T helper cell differentiation and Treg cell differentiation. Treatment with exosome injection or bone marrow mesenchymal stem cell (BMSC) transplantation reduce joint damage in RA. But the precise regulatory mechanisms remain unclear. METHODS: We injected BMSC-derived exosomes into RA mice, and then performed histological analysis on mouse ankle joints. We cultured CD4+ T cells in vitro, then added exosomes with or without si-TUG1 and induced the differentiation of Th17 cells and Treg cells, and then we used flow cytometry to detect the ratio of Th17 cells and Treg cells. Furthermore, we injected exosomes into sh-NC or sh-BLIMP1-treated RA mice, and then performed histological analysis on the ankle joints. RESULT: The results of our study demonstrate that exosome treatment decreased the proportion of differentiated Th17 cells, while increasing the proportion of Treg cells. And we observed that the Exo si-TUG1 group had an increased proportion of Th17 cells and a decreased proportion of Treg cells. We observed an increase in BLIMP1 expression in both the peripheral blood of mice and in CD4+ T cells cultured in vitro in the Exo group. Conversely, the Exo si-TUG1 group showed a decrease in BLIMP1 expression. Notably, inhibiting BLIMP1 expression led to the reversal of the therapeutic effects of exosomes. CONCLUSION: Our findings suggest that BMSC-derived exosomes promote the expression of BLIMP1 through Lnc TUG1-carrying exosomes, which may modulate the balance between Th17 cells and Treg cells. This mechanism ultimately alleviates damage caused by RA, suggesting that BMSC-derived exosomes enriched in Lnc TUG1 hold promise as a potential therapeutic approach for treating RA.


Subject(s)
Arthritis, Experimental , Arthritis, Rheumatoid , Cell Differentiation , Exosomes , Mesenchymal Stem Cells , Positive Regulatory Domain I-Binding Factor 1 , RNA, Long Noncoding , T-Lymphocytes, Regulatory , Th17 Cells , Animals , Th17 Cells/immunology , T-Lymphocytes, Regulatory/immunology , Exosomes/metabolism , Positive Regulatory Domain I-Binding Factor 1/genetics , Positive Regulatory Domain I-Binding Factor 1/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Arthritis, Experimental/therapy , Arthritis, Experimental/immunology , Mesenchymal Stem Cells/immunology , Mesenchymal Stem Cells/metabolism , Arthritis, Rheumatoid/therapy , Arthritis, Rheumatoid/immunology , Mice , Male , Cells, Cultured , Mice, Inbred DBA , Humans
9.
Biochem Biophys Res Commun ; 733: 150686, 2024 Nov 12.
Article in English | MEDLINE | ID: mdl-39278093

ABSTRACT

Our study aims to explore the effects of neoadjuvant chemotherapy (NACT) on tumour cells and immune cells in the immune microenvironment of patients with high-grade serous ovarian cancer (HGSOC). Single-cell RNA sequencing data of paired ovarian cancer tissues were analysed before and after NACT in 11 patients with HGSOC. The effect of NACT on two major cell components of the tumour microenvironment, epithelial cells and CD8+T cells, was investigated. The mechanisms of epithelial cell evasion by NACT and immune killing were explored from the perspectives of gene expression, functional characteristics, transcriptional regulation, and cell communication. Key targets for reversing NACT resistance were identified and possible therapeutic strategies proposed. While NACT improved the de novo differentiation of anti-tumour CD8+T cells, enhancing their anti-tumour function, it increased the proportion of cancer cells with high HSP90B1 expression. Thus, the potential reasons for NACT resistance were identified as: 1) high levels of endoplasmic reticulum stress (ERS) characteristics, 2) high expression of the MDK-NCL ligand-receptor pair between them and exhausted CD8+T cells before NACT, and 3) high expression of the NECTIN2-TIGIT immune ligand-receptor pair between them and exhausted CD8+T cells after NACT. Thus, our study reveals the mechanisms underlying NACT resistance in patients with HGSOC from the perspective of the independent and interactive roles of cancer cells and CD8+T cells. We propose therapeutic strategies targeting the ERS marker HSP90B1 and the immune escape marker MDK before or during NACT, while targeting NECTIN2 blockade after NACT. This approach may offer new insights into combination treatments for patients with HGSOC displaying NACT resistance.


Subject(s)
CD8-Positive T-Lymphocytes , Drug Resistance, Neoplasm , Endoplasmic Reticulum Stress , Neoadjuvant Therapy , Ovarian Neoplasms , Humans , Female , Ovarian Neoplasms/immunology , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathology , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/metabolism , Drug Resistance, Neoplasm/immunology , Drug Resistance, Neoplasm/drug effects , Endoplasmic Reticulum Stress/drug effects , Endoplasmic Reticulum Stress/immunology , Neoadjuvant Therapy/methods , Tumor Escape/drug effects , Tumor Microenvironment/drug effects , Tumor Microenvironment/immunology , Middle Aged
10.
Article in English | MEDLINE | ID: mdl-39349308

ABSTRACT

BACKGROUND AND PURPOSE: It remains unclear whether the combination of endovascular treatment (EVT) with intravenous thrombolysis (IVT) results in a more favorable functional outcome than EVT alone in managing cases of acute ischemic stroke (AIS) caused by basilar artery occlusion (BAO). Thus, this study aimed to compare the outcomes of two approaches-direct EVT (DEVT) and bridging therapy (IVT plus EVT)-in acute BAO patients presenting within 4.5 hours of stroke onset. MATERIALS AND METHODS: This multicenter retrospective cohort study included 153 acute BAO patients presenting within 4.5 hours of stroke onset. Of these patients, 65 (42.5%) and 88 (57.5%) underwent DEVT and bridging therapy, respectively. The primary outcome was defined as good functional outcome (modified Rankin Scale, 0-3) at 90 days. Additionally, pre-operative clinical features, thrombectomy attempts, successful reperfusion rates, incidences of symptomatic intracranial hemorrhage (sICH), and mortality were compared between the two groups. RESULTS: At 90 days, the rate of good functional outcome was comparable between the DEVT (44.6%) and bridging-therapy (39.8%) groups (adjusted odds ratio [aOR], 1.12; 95% confidence interval [CI], 0.55-2.31; p = 0.753). The bridging-therapy group exhibited a lower percentage of patients requiring ≥ 3 attempts of stent retrieval (aOR, 0.39; 95% CI, 0.16-0.93; p = 0.034). Pre-operative clinical features, rate of successful reperfusion, sICH, and mortality were similar between the two groups. CONCLUSIONS: In patients with BAO-induced AIS, DEVT demonstrates a comparable functional outcome to bridging therapy within 4.5 hours of symptom onset, but IVT reduces the number of thrombectomy attempts. ABBREVIATIONS: AIS, acute ischemic stroke; LVO, large-vessel occlusion; EVT, endovascular treatment; IVT, intravenous thrombolysis; BAO, basilar artery occlusion; DEVT, direct endovascular treatment; sICH, symptomatic intracranial hemorrhage; RCT, randomized controlled trial; IRIS, Improving Reperfusion Strategies in Ischemic Stroke; TOAST, Trial of ORG 10172 in Acute Stroke Treatment; mTICI, modified thrombolysis in cerebral infarction; SD, standard deviation; IQR, interquartile range; ICAS, intracranial atherosclerotic stenosis.

11.
J Org Chem ; 2024 Sep 30.
Article in English | MEDLINE | ID: mdl-39344782

ABSTRACT

A spiroannulation reaction of ß-ketothioamides with aromatic ß-bromoenals and aromatic α-bromoenals via selective C-Michael addition and S-Michael addition-triggered cascade reactions has been developed. This protocol provides a novel and rapid approach for the synthesis of substituted spirothiopyran and spirothiophene derivatives under mild conditions with moderate to good yields and a broad substrate scope.

12.
Cancer Lett ; 604: 217232, 2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39276913

ABSTRACT

Ferroptosis is a newly defined form of programmed cell death characterized by iron-dependent lipid peroxide accumulation and is associated with the progression of cancer. Solute carrier family 7 member 11 (SLC7A11), a key component of cystine/glutamate antiporter, has been characterized as a critical regulator of ferroptosis. Although many studies have established the transcriptional regulation of SLC7A11, it remains largely unknown how the stability of SLC7A11 is regulated in cancers, especially in triple-negative breast cancer (TNBC). Here we demonstrated that ovarian tumor domain-containing protein 5 (OTUD5), which deubiquitinated and stabilized SLC7A11, played a key role in TNBC progression and paclitaxel chemosensitivity through modulating ferroptosis. The clinical data analysis showed OTUD5 was higher expressed in TNBC, which positively correlated with SLC7A11 level. Mechanistically, OTUD5 interacted with SLC7A11 and cleaved K48-linked polyubiquitin chains from SLC7A11 to enhance the stability of SLC7A11. Taken together, these findings uncover a functional and mechanistic role of OTUD5 in TNBC progression and paclitaxel sensitivity, indicating OTUD5 could be a potential target for TNBC treatment.

13.
Front Neurosci ; 18: 1430465, 2024.
Article in English | MEDLINE | ID: mdl-39323915

ABSTRACT

Alzheimer's disease (AD) is increasingly recognized as being intertwined with the dysregulation of lipid metabolism. Lipids are a significant class of nutrients vital to all organisms, playing crucial roles in cellular structure, energy storage, and signaling. Alterations in the levels of various lipids in AD brains and dysregulation of lipid pathways and transportation have been implicated in AD pathogenesis. Clinically, evidence for a high-fat diet firmly links disrupted lipid metabolism to the pathogenesis and progression of AD, although contradictory findings warrant further exploration. In view of the significance of various lipids in brain physiology, the discovery of complex and diverse mechanisms that connect lipid metabolism with AD-related pathophysiology will bring new hope for patients with AD, underscoring the importance of lipid metabolism in AD pathophysiology, and promising targets for therapeutic intervention. Specifically, cholesterol, sphingolipids, and fatty acids have been shown to influence amyloid-beta (Aß) accumulation and tau hyperphosphorylation, which are hallmarks of AD pathology. Recent studies have highlighted the potential therapeutic targets within lipid metabolism, such as enhancing apolipoprotein E lipidation, activating liver X receptors and retinoid X receptors, and modulating peroxisome proliferator-activated receptors. Ongoing clinical trials are investigating the efficacy of these strategies, including the use of ketogenic diets, statin therapy, and novel compounds like NE3107. The implications of these findings suggest that targeting lipid metabolism could offer new avenues for the treatment and management of AD. By concentrating on alterations in lipid metabolism within the central nervous system and their contribution to AD development, this review aims to shed light on novel research directions and treatment approaches for combating AD, offering hope for the development of more effective management strategies.

14.
J Stroke Cerebrovasc Dis ; 33(12): 108029, 2024 Sep 21.
Article in English | MEDLINE | ID: mdl-39307209

ABSTRACT

BACKGROUND AND PURPOSE: Malnutrition is associated with poor outcomes in different diseases. Our aim was to investigate whether measures of malnutrition could be used to predict 90-day outcomes in patients with vertebrobasilar artery occlusion (VBAO) undergoing endovascular treatment (EVT). METHODS: We retrospectively analyzed patients with VBAO who received EVT at three comprehensive stroke centers. Malnutrition was assessed using the controlling nutritional status (CONUT) score, geriatric nutritional risk index (GNRI), and prognostic nutritional index (PNI). Primary outcome was good functional outcome defined as modified Rankin Scale (mRS) 0-3 measured at 90 days. RESULTS: A total of 285 patients were enrolled, of which 260 (91.22 %) met the requirements. According to the CONUT, GNRI, and PNI scores, the proportions of patients classified as moderately or severely malnourished were 7.3 %, 3.08 %, and 35 %, respectively. In the multivariate regression model after adjusting for potential confounders, malnutrition (severe risk versus normal nutritional status) was significantly associated with an increased risk of poor prognosis for CONUT scores (adjusted odds ratio [OR]14.91, 95 %CI, 1.69 - 131.71; P = 0.015), GNRI scores (adjusted [OR] 10.67, 1.17 - 96.93; P = 0.036) and PNI scores (adjusted [OR] 4.61, 2.28 - 9.31; P < 0.001). Similar results were obtained when malnutrition scores were analyzed as continuous variables. Adding the 3 malnutrition measures to the risk reclassification that included traditional risk factors significantly improved the predictive value of 3-month poor prognosis. CONCLUSIONS: Our study showed that malnutrition may be associated with poor prognosis within 3 months of EVT in patients with VBAO.

15.
Int J Mol Sci ; 25(17)2024 Aug 23.
Article in English | MEDLINE | ID: mdl-39273087

ABSTRACT

Activating enhancer-binding protein 2 (AP-2) is a family of transcription factors (TFs) that play crucial roles in regulating embryonic and oncogenic development. In addition to splice isoforms, five major family members encoded by the TFAP2A/B/C/D/E genes have been identified in humans, i.e., AP-2α/ß/γ/δ/ε. In general, the first three TFs have been studied more thoroughly than AP-2δ or AP-2ε. Currently, there is a relatively limited body of literature focusing on the AP-2 family in the context of gastroenterological research, and a comprehensive overview of the existing knowledge and recommendations for further research directions is lacking. Herein, we have collected available gastroenterological data on AP-2 TFs, discussed the latest medical applications of each family member, and proposed potential future directions. Research on AP-2 in gastrointestinal tumors has predominantly been focused on the two best-described family members, AP-2α and AP-2γ. Surprisingly, research in the past decade has highlighted the importance of AP-2ε in the drug resistance of gastric cancer (GC) and colorectal cancer (CRC). While numerous questions about gastroenterological disorders await elucidation, the available data undoubtedly open avenues for anti-cancer targeted therapy and overcoming chemotherapy resistance. In addition to gastrointestinal cancers, AP-2 family members (primarily AP-2ß and marginally AP-2γ) have been associated with other health issues such as obesity, type 2 diabetes, liver dysfunction, and pseudo-obstruction. On the other hand, AP-2δ has been poorly investigated in gastroenterological disorders, necessitating further research to delineate its role. In conclusion, despite the limited attention given to AP-2 in gastroenterology research, pivotal functions of these transcription factors have started to emerge and warrant further exploration in the future.


Subject(s)
Transcription Factor AP-2 , Humans , Transcription Factor AP-2/metabolism , Transcription Factor AP-2/genetics , Gastrointestinal Diseases/genetics , Gastrointestinal Diseases/metabolism , Animals
16.
Front Cell Infect Microbiol ; 14: 1405789, 2024.
Article in English | MEDLINE | ID: mdl-39220285

ABSTRACT

Background: Vaginal microbiota is involved in human papillomavirus (HPV) infection and cervical cancer (CC) progression, and the specific changes in vaginal microbial composition during this process remains uncertain. Objective: This study aimed to observe the changes in the specific composition of vaginal microorganisms in different cervical lesions and identify biomarkers at different stages of lesions. Methods: In this study we used the illumina high-throughput gene sequencing technology to determine the V4 region of 16SrRNA and observed the vaginal microbial composition in different cervical lesions. Results: The vaginal microbiota of patients with high-risk HPV infection and cervical lesions is significantly different from that of the normal population, but there is no significant difference in the richness of vaginal microbes. The diversity of vaginal species in CC patients is higher than that in high-risk HPV infection or CIN patients. The main manifestation is an increase in the diversity of vaginal microbes, a decrease in the relative abundance of cyanobacteria and Lactobacillus, and an increase in the relative abundance of dialister, peptonephila and other miscellaneous bacteria. There are characteristic vaginal biomarker in normal women, high risk HPV patients and CC patients. In detail, the biomarker in the normal group was varibaculum, the biomarker in the high-risk HPV group was saccharopolyspora, the biomarker of the CC group was the Proteobacteria, Corynebacterium, Coprococcus, Peptococcus and Ruminococcus. Conclusions: The study indicated that the compositions of vaginal microbes in different cervical lesions is different. The vaginal microbial composition has a certain diagnostic effect on healthy women, patients with high-risk HPV infection and cervical lesions. These microbes may serve as potential biomarkers for CC. It also provided an effective way for the treatment of HPV infections and cervical lesions.


Subject(s)
Bacteria , Microbiota , Papillomavirus Infections , RNA, Ribosomal, 16S , Uterine Cervical Neoplasms , Vagina , Humans , Female , Vagina/microbiology , Vagina/virology , Papillomavirus Infections/virology , Uterine Cervical Neoplasms/virology , Uterine Cervical Neoplasms/microbiology , Adult , RNA, Ribosomal, 16S/genetics , Bacteria/classification , Bacteria/isolation & purification , Bacteria/genetics , Middle Aged , High-Throughput Nucleotide Sequencing , Papillomaviridae/genetics , Papillomaviridae/isolation & purification , Young Adult , Cervix Uteri/virology , Cervix Uteri/microbiology , Cervix Uteri/pathology
17.
J Environ Manage ; 370: 122546, 2024 Sep 18.
Article in English | MEDLINE | ID: mdl-39299120

ABSTRACT

To improve the treatment performance of constructed wetlands under low-temperature conditions, this study investigated the effects of plant species on wastewater treatment performance at low temperature and the associated microbiological characteristics in a subsurface vertical-flow constructed wetland (VFCW) with step-feeding. The results showed that the redox microenvironment in the VFCW filter with step-feeding could be restored and optimized by planting appropriate species that can tolerate low temperature, ensuring a high nitrification performance for the system. Correspondingly, the abundance and activity of three functional microbes (namely nitrifiers, denitrifiers, and anammox bacteria) increased to different degrees in the system, eventually ensuring ideal nitrogen removal by the VFCW. Compared with the VFCW planted with Phragmites australis and Acorus gramineus, the operation performance of the VFCW planted with Iris wilsonii could be recovered at low temperature, and its chemical oxygen demand, total phosphorus, total nitrogen, and ammonium nitrate removal rates could respectively reach 95.7%, 99.2%, 93.0%, and 94.4%, respectively. Moreover, nitrogen removal in the system relied on the nitrification/denitrification and partial denitrification - anaerobic ammonium oxidation processes. Nitrosomonas, Nitrospira, Thauera, and Candidatus Brocadia were the four dominant bacterial genera in the filter layer.

18.
Article in English | MEDLINE | ID: mdl-39301997

ABSTRACT

The stepped care model (SCM) is a patient-centred approach to mental health care, offering a range of services from least to most intensive, tailored to individual needs. This scoping review examines the adoption, effectiveness, challenges and implications associated with applying SCM within primary mental health service delivery. Evidence from global sources suggests the model is viable, effective and useful. This review explores the literature available, clarifies fundamental concepts and identifies existing knowledge gaps. The literature search included CINAHL, MEDLINE, PsycINFO, Scopus, the Federation University library, Google and Google Scholar databases. A systematic keyword-based search using terms like "stepped care model," "mental health," and "primary care"; and a combination of keywords and subject headings, were used. The search strategy was refined by considering factors such as relevance, publication date, objectives and outcomes. This strategy yielded 20 papers compiled in this review. They include randomised controlled trials and cross-sectional studies. The review supports SCM adoption in primary mental health care but acknowledges the need for further research. Key inclusions of the review include cost-effectiveness, diverse diagnoses, efficacy and the model's structural configuration. Clear treatment details, delivery methods, intervention durations and chronological sequences are essential. This systematic approach enhances generalisability across different SCM models and areas, strengthening reliable inferences. In summary, the SCM holds promise for enhancing mental health service delivery. However, there is a need to further examine the factors that determine its effectiveness and understand the different ways in which SCM is implemented. Such inquiry forms the foundation for implementing and advancing mental health care services in Australia and internationally.

19.
JMIR Med Educ ; 10: e54105, 2024 Sep 13.
Article in English | MEDLINE | ID: mdl-39269365

ABSTRACT

Background: Australian nursing programs aim to introduce students to digital health requirements for practice. However, innovation in digital health is more dynamic than education providers' ability to respond. It is uncertain whether what is taught and demonstrated in nursing programs meets the needs and expectations of clinicians with regard to the capability of the nurse graduates. Objective: This study aims to identify gaps in the National Nursing and Midwifery Digital Health Capability Framework , based on the perspectives of clinical nurses, and in nurse educators' confidence and knowledge to teach. The findings will direct a future co-design process. Methods: This study triangulated the findings from 2 studies of the Digital Awareness in Simulated Health project and the National Nursing and Midwifery Digital Capability Framework. The first was a qualitative study that considered the experiences of nurses with digital health technologies during the COVID-19 pandemic, and the second was a survey of nurse educators who identified their confidence and knowledge to teach and demonstrate digital health concepts. Results: The results were categorized by and presented from the perspectives of nurse clinicians, nurse graduates, and nurse educators. Findings were listed against each of the framework capabilities, and omissions from the framework were identified. A series of statements and questions were formulated from the gap analysis to direct a future co-design process with nursing stakeholders to develop a digital health capability curriculum for nurse educators. Conclusions: Further work to evaluate nursing digital health opportunities for nurse educators is indicated by the gaps identified in this study.


Subject(s)
Curriculum , Education, Nursing , Humans , Australia , COVID-19/epidemiology , Qualitative Research , Female , Digital Technology , Digital Health
20.
BMC Genomics ; 25(1): 852, 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39261785

ABSTRACT

BACKGROUND: Low levels of the essential amino acid lysine in maize endosperm is considered to be a major problem regarding the nutritional quality of food and feed. Increasing the lysine content of maize is important to improve the quality of food and feed nutrition. Although the genetic basis of quality protein maize (QPM) has been studied, the further exploration of the quantitative trait loci (QTL) underlying lysine content variation still needs more attention. RESULTS: Eight maize inbred lines with increased lysine content were used to construct four double haploid (DH) populations for identification of QTLs related to lysine content. The lysine content in the four DH populations exhibited continuous and normal distribution. A total of 12 QTLs were identified in a range of 4.42-12.66% in term of individual phenotypic variation explained (PVE) which suggested the quantitative control of lysine content in maize. Five main genes involved in maize lysine biosynthesis pathways in the QTL regions were identified in this study. CONCLUSIONS: The information presented will allow the exploration of candidate genes regulating lysine biosynthesis pathways and be useful for marker-assisted selection and gene pyramiding in high-lysine maize breeding programs.


Subject(s)
Lysine , Quantitative Trait Loci , Zea mays , Zea mays/genetics , Zea mays/metabolism , Lysine/metabolism , Phenotype , Haploidy , Chromosome Mapping
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