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1.
Front Plant Sci ; 15: 1401050, 2024.
Article in English | MEDLINE | ID: mdl-38974980

ABSTRACT

Introduction: Drought stress usually inhibits plant growth, which may increase the difficulty of greening slopes. Methods: In this study, we systematically investigated the effects of arbuscular mycorrhizal (AM) fungi on the growth and drought tolerance of two plant species, Festuca elata and Cassia glauca, in a vegetation concrete environment by exogenously inoculating AM fungi and setting three drought levels: well water, moderate drought and severe drought. The results showed that plant growth was significantly inhibited under drought stress; however, AM fungi inoculation significantly promoted plant height, root length, and above- and belowground biomass in these two plant species. Results: Compared with, those in the CK treatment, the greatest increases in the net photosynthesis rate, stomatal conductance and transpiration rate in the AM treatment group were 36.72%, 210.08%, and 66.41%, respectively. Moreover, inoculation with AM fungi increased plant superoxide dismutase and catalase activities by 4.70-150.73% and 9.10-95.70%, respectively, and reduced leaf malondialdehyde content by 2.79-55.01%, which alleviated the damage caused by oxidative stress. These effects alleviated the damage caused by oxidative stress and increased the content of soluble sugars and soluble proteins in plant leaves by 1.52-65.44% and 4.67-97.54%, respectively, which further increased the drought adaptability of plants. However, inoculation with AM fungi had different effects on different plants. Conclusion: In summary, this study demonstrated that the inoculation of AM fungi in vegetation concrete environments can significantly increase plant growth and drought tolerance. The plants that formed a symbiotic structure with AM fungi had a larger root uptake area, greater water uptake capacity, and greater photosynthesis and gas exchange efficiency. In addition, AM fungi inoculation further increased the drought adaptability of the plants by increasing their antioxidant enzyme activity and regulating their metabolite content. These findings are highly important for promoting plant growth and increasing drought tolerance under drought conditions, especially for potential practical applications in areas such as slope protection, and provide useful references for future ecological engineering and sustainable development.

2.
BMC Nurs ; 23(1): 426, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38918789

ABSTRACT

BACKGROUND: The experiences and perceptions of geriatric specialist nurses are pivotal to understanding the complexities of managing delirium and to developing effective nursing interventions. This qualitative study aims to explore these experiences and perceptions to inform the enhancement of clinical geriatric nursing and care practices. METHODS: Utilizing a qualitative exploratory design, this research engaged a convenience sample of geriatric specialist nurses at a tertiary hospital in Shanghai, China through focus groups and semi-structured interviews. Data were rigorously analyzed using Colaizzi's phenomenological method, which facilitated the identification of themes that emerged from the narratives of the geriatric specialist nurses. RESULTS: The thematic analysis yielded three major themes that encapsulate the nurses' experiences and perceptions. Theme 1: Understanding of Delirium, highlighted the nurses' awareness of the condition's significance, yet it was often deprioritized due to the pressing demands of managing more acute and immediately life-threatening conditions. Theme 2: Barriers in Application, brought to light the multifaceted challenges faced by nurses, including language barriers, the frequency and consistency of delirium assessments, the social determinants of health, and the nurses' own competencies in assessment. Theme 3: Evolution of Nursing Approaches, detailed the adaptive strategies employed by nurses, such as managing nursing adverse events, improving communication with patients' families, and adopting a proactive stance towards long-term patient outcomes. CONCLUSIONS: The findings suggest that while geriatric specialist nurses recognize the importance of delirium assessment, there are several barriers to effective application. The study underscores the imperative for the advancement of more refined delirium assessment and care protocols, tailored to address the unique requirements of geriatric nursing care.

3.
Science ; 384(6702): 1373-1380, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38900890

ABSTRACT

The oxygen evolution reaction is the bottleneck to energy-efficient water-based electrolysis for the production of hydrogen and other solar fuels. In proton exchange membrane water electrolysis (PEMWE), precious metals have generally been necessary for the stable catalysis of this reaction. In this work, we report that delamination of cobalt tungstate enables high activity and durability through the stabilization of oxide and water-hydroxide networks of the lattice defects in acid. The resulting catalysts achieve lower overpotentials, a current density of 1.8 amperes per square centimeter at 2 volts, and stable operation up to 1 ampere per square centimeter in a PEMWE system at industrial conditions (80°C) at 1.77 volts; a threefold improvement in activity; and stable operation at 1 ampere per square centimeter over the course of 600 hours.

4.
Clin Chim Acta ; 561: 119761, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38848897

ABSTRACT

BACKGROUND: Determination of DPYD and UGT1A1 polymorphisms prior to 5-fluorouracil and irinotecan therapy is crucial for avoiding severe adverse drug effects. Hence, there is a pressing need for accurate and reliable genotyping methods for the most common DPYD and UGT1A1 polymorphisms. In this study, we introduce a novel polymerase chain reaction (PCR) melting curve analysis method for discriminating DPYD c.1236G > A, c.1679 T > G, c.2846A > T, IVS14 + 1G > A and UGT1A1*1, *28, *6 (G71R) genotypes. METHODS: Following protocol optimization, this technique was employed to genotype 28 patients, recruited between March 2023 and October 2023, at the First Affiliated Hospital of Xiamen University. These patients included 20 with UGT1A1 *1/*1, 8 with UGT1A1 *1/*28, 4 with UGT1A1 *28/*28, 22 with UGT1A1*6 G/G, 6 with UGT1A1*6 G/A, 4 with UGT1A1*6 A/A, 27 with DPYD(c.1236) G/G, 3 with DPYD(c.1236) G/A, 2 with DPYD(c.1236) A/A, 27 with DPYD(c.1679) T/T, 2 with DPYD(c.1679) T/G, 3 with DPYD(c.1679) G/G, 28 with DPYD(c.2846A/T) A/A, 2 with DPYD(c.2846A/T) A/T, 2 with DPYD(c.2846A/T) T/T, 28 with DPYD(c.IVS14 + 1) G/G, 2 with DPYD(c.IVS14 + 1) G/G, and 2 with DPYD(c.IVS14 + 1) G/G, as well as 3 plasmid standards. Method accuracy was assessed by comparing results with those from Sanger sequencing or Multiplex quantitative PCR(qPCR). Intra- and inter-run precision of melting temperatures (Tms) were calculated to evaluate reliability, and sensitivity was assessed through limit of detection examination. RESULTS: The new method accurately identified all genotypes and exhibited higher accuracy than Multiplex qPCR. Intra- and inter-run coefficients of variation for Tms were both ≤1.97 %, with standard deviations ≤0.95 °C. The limit of detection was 0.09 ng/µL of input genomic DNA. CONCLUSION: Our developed PCR melting curve analysis offers accurate, reliable, rapid, simple, and cost-effective detection of DPYD and UGT1A1 polymorphisms. Its application can be easily extended to clinical laboratories equipped with a fluorescent PCR platform.

5.
Proc Natl Acad Sci U S A ; 121(23): e2403796121, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38809710

ABSTRACT

Olfactory receptors (Olfr) are G protein-coupled receptors that are normally expressed on olfactory sensory neurons to detect volatile chemicals or odorants. Interestingly, many Olfrs are also expressed in diverse tissues and function in cell-cell recognition, migration, and proliferation as well as immune responses and disease processes. Here, we showed that many Olfr genes were expressed in the mouse spleen, linked to Plasmodium yoelii genetic loci significantly, and/or had genome-wide patterns of LOD scores (GPLSs) similar to those of host Toll-like receptor genes. Expression of specific Olfr genes such as Olfr1386 in HEK293T cells significantly increased luciferase signals driven by IFN-ß and NF-κB promoters, with elevated levels of phosphorylated TBK1, IRF3, P38, and JNK. Mice without Olfr1386 were generated using the CRISPR/Cas9 method, and the Olfr1386-/- mice showed significantly lower IFN-α/ß levels and longer survival than wild-type (WT) littermates after infection with P. yoelii YM parasites. Inhibition of G protein signaling and P38 activity could affect cyclic AMP-responsive element promoter-driven luciferase signals and IFN-ß mRNA levels in HEK293T cells expressing the Olfr1386 gene, respectively. Screening of malaria parasite metabolites identified nicotinamide adenine dinucleotide (NAD) as a potential ligand for Olfr1386, and NAD could stimulate IFN-ß responses and phosphorylation of TBK1 and STAT1/2 in RAW264.7 cells. Additionally, parasite RNA (pRNA) could significantly increase Olfr1386 mRNA levels. This study links multiple Olfrs to host immune response pathways, identifies a candidate ligand for Olfr1386, and demonstrates the important roles of Olfr1386 in regulating type I interferon (IFN-I) responses during malaria parasite infections.


Subject(s)
Interferon Type I , Malaria , Plasmodium yoelii , Receptors, Odorant , Animals , Mice , Malaria/immunology , Malaria/parasitology , Malaria/metabolism , Humans , HEK293 Cells , Receptors, Odorant/genetics , Receptors, Odorant/metabolism , Interferon Type I/metabolism , Interferon Type I/immunology , Mice, Knockout , Signal Transduction , Mice, Inbred C57BL
6.
Microbiol Spectr ; 12(6): e0391423, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38742903

ABSTRACT

Porcine parvovirus (PPV) is one of the most important pathogens that cause reproductive failure in pigs. However, the pathogenesis of PPV infection remains unclear. Proteomics is a powerful tool to understand the interaction between virus and host cells. In the present study, we analyzed the proteomics of PPV-infected PK-15 cells. A total of 32 and 345 proteins were differentially expressed at the early and replication stages, respectively. Subsequent gene ontology annotation and Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed these differentially expressed proteins were significantly enriched in pathways including toll-like receptor signaling pathway, tumor necrosis factor signaling pathway, and viral carcinogenesis. The expression of poly (rC) binding protein 1 (PCBP1) was observed to decrease after PPV infection. Overexpressed or silenced PCBP1 expression inhibited or promoted PPV infection. Our studies established a foundation for further exploration of the multiplication mechanism of PPV. IMPORTANCE: Porcine parvovirus (PPV) is a cause of reproductive failure in the swine industry. Our knowledge of PPV remains limited, and there is no effective treatment for PPV infection. Proteomics of PPV-infected PK-15 cells was conducted to identify differentially expressed proteins at 6 hours post-infection (hpi) and 36 hpi. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that various pathways participate in PPV infection. Poly (rC) binding protein 1 was confirmed to inhibit PPV replication, which provided potential targets for anti-PPV infection. Our findings improve the understanding of PPV infection and pave the way for future research in this area.


Subject(s)
Parvoviridae Infections , Parvovirus, Porcine , Proteomics , RNA-Binding Proteins , Swine Diseases , Virus Replication , Parvovirus, Porcine/genetics , Parvovirus, Porcine/physiology , Animals , Swine , Cell Line , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , Parvoviridae Infections/virology , Parvoviridae Infections/metabolism , Parvoviridae Infections/veterinary , Swine Diseases/virology , Swine Diseases/metabolism , Swine Diseases/genetics , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism
7.
Biosci Rep ; 2024 May 07.
Article in English | MEDLINE | ID: mdl-38712547

ABSTRACT

Porcine deltacoronavirus (PDCoV) is an newly emerged enteropathogenic coronavirus, mainly causing diarrhea in suckling piglets, and also has the potential for cross-species transmission. However, there are no effective vaccines or specific therapeutic agents for PDCoV. This study investigates the antiviral properties of baicalein against PDCoV infection in swine testicle cells (ST). It reveals that baicalein exerts a dose-dependent inhibitory effect on PDCoV replication, primarily targeting the replication stage of the viral infection by impeding viral RNA and protein synthesis. Furthermore, treatment with baicalein leads to reduced phosphorylation of PI3K, AKT, and NF-κB p65 proteins, along with decreased mRNA levels of pro-inflammatory cytokines (IL-1ß, IL-6, IL-8, and TNF-α). These results signify that PDCoV replication is inhibited through the inhibition of the PI3K-Akt-NF-κB protein signaling pathway, thereby suppressing the inflammatory response. In conclusion, it underscores the potential of baicalein as a therapeutic candidate for treating PDCoV infection.

8.
Nat Nanotechnol ; 2024 May 13.
Article in English | MEDLINE | ID: mdl-38740933

ABSTRACT

Constructing effective antidotes to reduce global health impacts induced by alcohol prevalence is a challenging topic. Despite the positive effects observed with intravenous applications of natural enzyme complexes, their insufficient activities and complicated usage often result in the accumulation of toxic acetaldehyde, which raises important clinical concerns, highlighting the pressing need for stable oral strategies. Here we present an effective solution for alcohol detoxification by employing a biomimetic-nanozyme amyloid hydrogel as an orally administered catalytic platform. We exploit amyloid fibrils derived from ß-lactoglobulin, a readily accessible milk protein that is rich in coordinable nitrogen atoms, as a nanocarrier to stabilize atomically dispersed iron (ferrous-dominated). By emulating the coordination structure of the horseradish peroxidase enzyme, the single-site iron nanozyme demonstrates the capability to selectively catalyse alcohol oxidation into acetic acid, as opposed to the more toxic acetaldehyde. Administering the gelatinous nanozyme to mice suffering from alcohol intoxication significantly reduced their blood-alcohol levels (decreased by 55.8% 300 min post-alcohol intake) without causing additional acetaldehyde build-up. Our hydrogel further demonstrates a protective effect on the liver, while simultaneously mitigating intestinal damage and dysbiosis associated with chronic alcohol consumption, introducing a promising strategy in effective alcohol detoxification.

9.
Medicine (Baltimore) ; 103(21): e38203, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38788018

ABSTRACT

To analyze the correlation between Balthazar CT grading and contrast-enhanced CT necrosis volume and attenuation value and prognosis of patients with acute necrotizing pancreatitis. Ninety-two patients with acute necrotizing pancreatitis who were treated in the hospital were selected between June 2019 and June 2021, and they were divided into the poor prognosis group and the good prognosis group according to the clinical prognosis at 6 months of follow-up. Balthazar CT, contrast-enhanced CT necrosis volume, and attenuation value were compared between the 2 groups. Multivariate logistic regression analysis was used to analyze the influencing factors. Receiver operating characteristic curve was adopted to analyze the predictive value. Among the 92 participants, there were 28 cases with good prognosis (30.43%) and 64 cases with poor prognosis (69.57%). The Acute Physiology and Chronic Health Evaluation II score, C-reactive protein, urea nitrogen, Balthazar CT, necrotic volume, and average attenuation value of the poor prognosis group were significantly higher than those of the good prognosis group (all P values <.05). The results of the multivariate logistic analysis showed that Balthazar CT grade, necrotic volume, and average attenuation value were independent risk factors for poor prognosis in patients with acute necrotizing pancreatitis (all P values <.05). The area under the curve of Balthazar CT grade, necrotic volume, average attenuation value, and the joint detection in predicting the prognosis of patients with acute necrotizing pancreatitis were 0.765, 0.624, 0.764, and 0.861, respectively. The Balthazar CT grading, necrosis volume, and average attenuation value are significantly higher among patients with acute necrotizing pancreatitis complicated with poor prognosis, and they are also independent risk factors for poor prognosis in patients with acute necrotizing pancreatitis, and can help clinically predict the prognosis of patients with acute necrotizing pancreatitis, and the combined detection has better application effects.


Subject(s)
Pancreatitis, Acute Necrotizing , Tomography, X-Ray Computed , Humans , Pancreatitis, Acute Necrotizing/diagnostic imaging , Pancreatitis, Acute Necrotizing/mortality , Pancreatitis, Acute Necrotizing/pathology , Male , Female , Middle Aged , Tomography, X-Ray Computed/methods , Prognosis , Adult , Necrosis/diagnostic imaging , ROC Curve , Aged , Severity of Illness Index , Retrospective Studies , Risk Factors , Contrast Media , Predictive Value of Tests
10.
BMC Cancer ; 24(1): 561, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38711034

ABSTRACT

Modulation of DNA damage repair in lung squamous cell carcinoma (LUSC) can result in the generation of neoantigens and heightened immunogenicity. Therefore, understanding DNA damage repair mechanisms holds significant clinical relevance for identifying targets for immunotherapy and devising therapeutic strategies. Our research has unveiled that the tumor suppressor zinc finger protein 750 (ZNF750) in LUSC binds to the promoter region of tenascin C (TNC), leading to reduced TNC expression. This modulation may impact the malignant behavior of tumor cells and is associated with patient prognosis. Additionally, single-cell RNA sequencing (scRNA-seq) of LUSC tissues has demonstrated an inverse correlation between ZNF750/TNC expression levels and immunogenicity. Manipulation of the ZNF750-TNC axis in vitro within LUSC cells has shown differential sensitivity to CD8+ cells, underscoring its pivotal role in regulating cellular immunogenicity. Further transcriptome sequencing analysis, DNA damage repair assay, and single-strand break analyses have revealed the involvement of the ZNF750-TNC axis in determining the preference for homologous recombination (HR) repair or non-homologous end joining (NHEJ) repair of DNA damage. with involvement of the Hippo/ERK signaling pathway. In summary, this study sheds light on the ZNF750-TNC axis's role in DNA damage repair regulation in LUSC, laying a groundwork for future translational research in immune cell therapy for LUSC.


Subject(s)
Carcinoma, Squamous Cell , DNA Damage , Lung Neoplasms , Tenascin , Humans , Lung Neoplasms/immunology , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Tenascin/genetics , Tenascin/metabolism , DNA Damage/immunology , Carcinoma, Squamous Cell/immunology , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Transcription Factors/metabolism , Transcription Factors/genetics , Promoter Regions, Genetic , Prognosis , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism
11.
Prev Med ; 185: 108021, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38821420

ABSTRACT

OBJECTIVE: Lifestyle factors after cancer diagnosis could influence cancer survival. This study aimed to investigate the joint effects of smoking, physical activity, alcohol consumption, diet and sleep duration on all-cause, cancer and non-cancer mortality of cancer survivors in UK biobank. METHODS: The follow-up period concluded in December 2021, with post-diagnostic lifestyle factors assessed at baseline. A lifestyle score ranging from 0 to 5 was assigned based on adherence to the selected lifestyle factors. The study employed Cox regression models for hazard ratios (HRs) and Kaplan-Meier for survival rates, with stratified and sensitivity analyses to assess the robustness of our findings under various assumptions. RESULTS: During a median follow-up of 12.7 years, 5652 deaths were documented from 34,184 cancer survivors. Compared to scoring 0-1, the HRs (95% CIs) for all-cause mortality with lifestyle scores of 2, 3, 4, and 5 were 0.70 (95% CI: 0.64, 0.76), 0.57 (0.52, 0.62), 0.50 (0.45, 0.54) and 0.43 (0.38, 0.48), respectively. Specific cancer types, particularly digestive, breast, female reproductive, non-solid, and skin cancers, showed notable benefits from adherence to healthy lifestyle, with the HRs of 0.55 (0.39, 0.79), 0.54 (0.42, 0.70), 0.32 (0.19, 0.53), 0.58 (0.39, 0.86), and 0.36 (0.28, 0.46) for lifestyle score of 5, respectively. Stratified analyses indicated the association was particularly significant among those with normal/lower BMI and higher Townsend Deprivation Index (Pinteraction = 0.001 and < 0.001, respectively). CONCLUSIONS: Healthier lifestyles were significantly linked with reduced mortality among cancer survivors. These findings highlight the need for adherence to healthy lifestyle habits to improve survival.

12.
Adv Mater ; : e2402090, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38776138

ABSTRACT

Vanadium redox flow batteries (VRFB) are a promising technology for large-scale storage of electrical energy, combining safety, high capacity, ease of scalability, and prolonged durability; features which have triggered their early commercial implementation. Furthering the deployment of VRFB technologies requires addressing challenges associated to a pivotal component: the membrane. Examples include vanadium crossover, insufficient conductivity, escalated costs, and sustainability concerns related to the widespread adoption of perfluoroalkyl-based membranes, e.g., perfluorosulfonic acid (PFSA). Herein, recent advances in high-performance and sustainable membranes for VRFB, offering insights into prospective research directions to overcome these challenges, are reviewed. The analysis reveals the disparities and trade-offs between performance advances enabled by PFSA membranes and composites, and the lack of sustainability in their final applications. The potential of PFSA-free membranes and present strategies to enhance their performance are discussed. This study delves into vital membrane parameters to enhance battery performance, suggesting protocols and design strategies to achieve high-performance and sustainable VRFB membranes.

13.
J Multidiscip Healthc ; 17: 1743-1754, 2024.
Article in English | MEDLINE | ID: mdl-38680878

ABSTRACT

Objective: To identify latent classes of preoperative physical dysfunction in elderly patients with early lung cancer. To analyze the differences in demographic characteristics between different classes. Methods: We invited elderly patients with early lung cancer who were scheduled for surgery at Shanghai Elderly Characteristic Hospital to participate in the study using a convenience sampling method. We took latent class analysis to divide elderly patients with early lung cancer into latent classes based on preoperative physical dysfunction features. Furthermore, we used single-factor analysis and multinomial logistic regression to investigate the influence variables of each latent class. Results: The characteristics of preoperative physical dysfunction in elderly patients with early lung cancer can be divided into "Anxiety/depression emotion-poor sleep group" "Frailty of physical function group" "Pulmonary hypofunction-low activity tolerance group". The distribution of age, chronic disease history, COPD history, smoking history and perceived social support level of elderly patients with early lung cancer in different potential categories were not the same, and the differences were statistically significant (P<0.05). The elderly lung cancer patients with chronic disease history and age ≥75 years were more likely to be classified as "frailty of physical function group". The elderly lung cancer patients with COPD and smoking history were more likely to be classified into "pulmonary hypofunction-low activity tolerance group". Elderly lung cancer patients with moderate or low degree of perceived social support were more prone to be grouped into "anxiety/depression emotion-poor sleep group". Conclusion: The variety of preoperative physical dysfunction seen in elderly patients with early lung cancer can be categorized into three latent classes. Medical professionals should create strategies for intervention for multiple patient populations with the goal of further enhancing their general state of life.

14.
Sci Rep ; 14(1): 9743, 2024 04 28.
Article in English | MEDLINE | ID: mdl-38679603

ABSTRACT

Recent studies focused on exploring phosphodiesterase type 5 inhibitors (PDE5Is)-related hearing impairment. This study aimed to comprehensively explore real-world hearing impairment associated with PDE5Is based on the US Food and Drug Administration Adverse Event Reporting System (FAERS). The characteristics and correlation of PDE5Is-related hearing impairment reported in the FAERS database from the fourth quarter of 2003 to the second quarter of 2023 were analyzed using disproportionality analysis. The Standardized Medical Dictionary for Regulatory Activities (MedDRA) Queries (SMQs) were used to analyze the adverse events (AEs) of hearing impairment. A total of 1,438 reported cases of hearing impairment were associated with four PDE5Is, revealing statistically significant reporting odds ratio (ROR), proportional reporting ratio (PRR), and information component (IC) with the SMQ. The average age of all patients was more than 55 years, over 70% of AEs were reported in men. Most of the reported cases were from the United States. Reports for all the drugs indicated an increase since 2008, except for avanafil. This study showed that the disability rates of PDE5Is were 8.14-40%, the rates of initial or prolonged hospitalization were 6.21-10.24%, and the rates of required intervention were 3.31-9.45%. The pharmacovigilance study identified a potential risk of hearing impairment associated with PDE5Is, indicating the need for continuous monitoring and appropriate management.


Subject(s)
Adverse Drug Reaction Reporting Systems , Hearing Loss , Phosphodiesterase 5 Inhibitors , United States Food and Drug Administration , Humans , United States/epidemiology , Male , Hearing Loss/chemically induced , Hearing Loss/epidemiology , Phosphodiesterase 5 Inhibitors/adverse effects , Adverse Drug Reaction Reporting Systems/statistics & numerical data , Middle Aged , Female , Aged , Adult , Databases, Factual
15.
Signal Transduct Target Ther ; 9(1): 96, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38653754

ABSTRACT

The translocation of YAP from the cytoplasm to the nucleus is critical for its activation and plays a key role in tumor progression. However, the precise molecular mechanisms governing the nuclear import of YAP are not fully understood. In this study, we have uncovered a crucial role of SOX9 in the activation of YAP. SOX9 promotes the nuclear translocation of YAP by direct interaction. Importantly, we have identified that the binding between Asp-125 of SOX9 and Arg-124 of YAP is essential for SOX9-YAP interaction and subsequent nuclear entry of YAP. Additionally, we have discovered a novel asymmetrical dimethylation of YAP at Arg-124 (YAP-R124me2a) catalyzed by PRMT1. YAP-R124me2a enhances the interaction between YAP and SOX9 and is associated with poor prognosis in multiple cancers. Furthermore, we disrupted the interaction between SOX9 and YAP using a competitive peptide, S-A1, which mimics an α-helix of SOX9 containing Asp-125. S-A1 significantly inhibits YAP nuclear translocation and effectively suppresses tumor growth. This study provides the first evidence of SOX9 as a pivotal regulator driving YAP nuclear translocation and presents a potential therapeutic strategy for YAP-driven human cancers by targeting SOX9-YAP interaction.


Subject(s)
Adaptor Proteins, Signal Transducing , Cell Nucleus , SOX9 Transcription Factor , Transcription Factors , YAP-Signaling Proteins , Humans , YAP-Signaling Proteins/genetics , YAP-Signaling Proteins/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Adaptor Proteins, Signal Transducing/genetics , Adaptor Proteins, Signal Transducing/metabolism , Cell Nucleus/metabolism , Cell Nucleus/genetics , SOX9 Transcription Factor/genetics , SOX9 Transcription Factor/metabolism , Protein-Arginine N-Methyltransferases/genetics , Protein-Arginine N-Methyltransferases/metabolism , Neoplasms/genetics , Neoplasms/metabolism , Neoplasms/pathology , Active Transport, Cell Nucleus/genetics , Mice , Cell Line, Tumor , Animals , Repressor Proteins/genetics , Repressor Proteins/metabolism
16.
JCI Insight ; 9(9)2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38592784

ABSTRACT

Recent studies have uncovered that noncoding sequence variants may relate to Axenfeld-Rieger syndrome (ARS), a rare developmental anomaly with genetic heterogeneity. However, how these genomic regions are functionally and structurally associated with ARS is still unclear. In this study, we performed genome-wide linkage analysis and whole-genome sequencing in a Chinese family with ARS and identified a heterozygous deletion of about 570 kb (termed LOH-1) in the intergenic sequence between paired-like homeodomain transcription factor 2 (PITX2) and family with sequence similarity 241 member A. Knockout of LOH-1 homologous sequences caused ARS phenotypes in mice. RNA-Seq and real-time quantitative PCR revealed a significant reduction in Pitx2 gene expression in LOH-1-/- mice, while forkhead box C1 expression remained unchanged. ChIP-Seq and bioinformatics analysis identified a potential enhancer region (LOH-E1) within LOH-1. Deletion of LOH-E1 led to a substantial downregulation of the PITX2 gene. Mechanistically, we found a sequence (hg38 chr4:111,399,594-111,399,691) that is on LOH-E1 could regulate PITX2 by binding to RAD21, a critical component of the cohesin complex. Knockdown of RAD21 resulted in reduced PITX2 expression. Collectively, our findings indicate that a potential enhancer sequence that is within LOH-1 may regulate PITX2 expression remotely through cohesin-mediated loop domains, leading to ARS when absent.


Subject(s)
Anterior Eye Segment , Eye Abnormalities , Eye Diseases, Hereditary , Homeobox Protein PITX2 , Homeodomain Proteins , Transcription Factors , Animals , Female , Humans , Male , Mice , Anterior Eye Segment/abnormalities , Anterior Eye Segment/metabolism , DNA, Intergenic/genetics , Enhancer Elements, Genetic/genetics , Eye Abnormalities/genetics , Eye Diseases, Hereditary/genetics , Homeodomain Proteins/genetics , Homeodomain Proteins/metabolism , Mice, Knockout , Pedigree , Transcription Factors/genetics , Transcription Factors/metabolism
17.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(3): 275-281, 2024 Mar 15.
Article in Chinese | MEDLINE | ID: mdl-38557380

ABSTRACT

OBJECTIVES: To investigate the nutritional status of children with cystic fibrosis (CF) and understand the correlation between malnutrition and clinical characteristics as well as lung function. METHODS: A retrospective analysis was performed on clinical data of CF children admitted from January 2016 to June 2023. Clinical characteristics of CF children with different nutritional statuses were compared, and the correlation between malnutrition and lung function was analyzed. RESULTS: A total of 52 CF children were included, comprising 25 boys (48%) and 27 girls (52%), aged between 7 months and 17 years. Respiratory symptoms were the predominant clinical manifestations (96%, 50/52). The prevalence of malnutrition was 65% (34/52), with moderate/severe malnutrition being the most common (65%, 22/34). The malnutrition group had a longer duration of illness, higher proportion of digestive system symptoms, and lower levels of serum albumin (P<0.05). Pulmonary function parameters, including forced expiratory volume in one second as a percentage of the predicted value, ratio of forced expiratory volume in one second to forced vital capacity, forced expiratory flow at 25% of forced vital capacity exhaled, forced expiratory flow at 50% of forced vital capacity exhaled, forced expiratory flow at 75% of forced vital capacity exhaled, and maximum mid-expiratory flow as a percentage of the predicted value, were lower in the malnutrition group compared to the normal nutrition group (P<0.05). Correlation analysis showed body mass index Z-score was positively correlated with the above six pulmonary function parameters (P<0.05). CONCLUSIONS: The prevalence of malnutrition is high in CF children and is associated with decreased lung function. CF children with higher body mass index have better lung function. Therefore, screening and evaluation of nutritional status as well as appropriate nutritional intervention should be emphasized in CF children.


Subject(s)
Cystic Fibrosis , Malnutrition , Child , Male , Female , Humans , Infant , Nutritional Status , Retrospective Studies , Cystic Fibrosis/complications , Lung , Forced Expiratory Volume , Malnutrition/etiology , Malnutrition/complications
18.
Materials (Basel) ; 17(7)2024 Apr 07.
Article in English | MEDLINE | ID: mdl-38612205

ABSTRACT

Aluminosilicates, such as montmorillonite, kaolinite, halloysite, and diatomite, have a uniform bidimensional structure, a high surface-to-volume ratio, inherent stiffness, a dual charge distribution, chemical inertness, biocompatibility, abundant active groups on the surface, such as silanol (Si-OH) and/or aluminol (Al-OH) groups. These compounds are on the list of U.S. Food and Drug Administration-approved active compounds and excipients and are used for various medicinal products, such as wound healing agents, antidiarrheals, and cosmetics. This review summarizes the wound healing mechanisms related to the material characteristics and the chemical components. Numerous wound dressings with different active components and multiple forms have been studied. Then, medicinal mineral resources for use in hemostatic materials can be developed.

19.
J Multidiscip Healthc ; 17: 1561-1575, 2024.
Article in English | MEDLINE | ID: mdl-38617080

ABSTRACT

Backgrounds: With the advent of the big data era, hospital information systems and mobile care systems, among others, generate massive amounts of medical data. Data mining, as a powerful information processing technology, can discover non-obvious information by processing large-scale data and analyzing them in multiple dimensions. How to find the effective information hidden in the database and apply it to nursing clinical practice has received more and more attention from nursing researchers. Aim: To look over the articles on data mining in nursing, compiled research status, identified hotspots, highlighted research trends, and offer recommendations for how data mining technology might be used in the nursing area going forward. Methods: Data mining in nursing publications published between 2002 and 2023 were taken from the Web of Science Core Collection. CiteSpace was utilized for reviewing the number of articles, countries/regions, institutions, journals, authors, and keywords. Results: According to the findings, the pace of data mining in nursing progress is not encouraging. Nursing data mining research is dominated by the United States and China. However, no consistent core group of writers or organizations has emerged in the field of nursing data mining. Studies on data mining in nursing have been increasingly gradually conducted in the 21st century, but the overall number is not large. Institution of Columbia University, journal of Cin-computers Informatics Nursing, author Diana J Wilkie, Muhammad Kamran Lodhi, Yingwei Yao are most influential in nursing data mining research. Nursing data mining researchers are currently focusing on electronic health records, text mining, machine learning, and natural language processing. Future research themes in data mining in nursing most include nursing informatics and clinical care quality enhancement. Conclusion: Research data shows that data mining gives more perspectives for the growth of the nursing discipline and encourages the discipline's development, but it also introduces a slew of new issues that need researchers to address.

20.
BMC Genomics ; 25(1): 368, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38622509

ABSTRACT

BACKGROUND: We recently developed two high-resolution methods for genome-wide mapping of two prominent types of DNA damage, single-strand DNA breaks (SSBs) and abasic (AP) sites and found highly complex and non-random patterns of these lesions in mammalian genomes. One salient feature of SSB and AP sites was the existence of single-nucleotide hotspots for both lesions. RESULTS: In this work, we show that SSB hotspots are enriched in the immediate vicinity of transcriptional start sites (TSSs) in multiple normal mammalian tissues, however the magnitude of enrichment varies significantly with tissue type and appears to be limited to a subset of genes. SSB hotspots around TSSs are enriched on the template strand and associate with higher expression of the corresponding genes. Interestingly, SSB hotspots appear to be at least in part generated by the base-excision repair (BER) pathway from the AP sites. CONCLUSIONS: Our results highlight complex relationship between DNA damage and regulation of gene expression and suggest an exciting possibility that SSBs at TSSs might function as sensors of DNA damage to activate genes important for DNA damage response.


Subject(s)
DNA Breaks, Single-Stranded , DNA Repair , Animals , DNA Repair/genetics , DNA Damage , DNA, Single-Stranded , Mammals
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