Nuclear receptor co-activator 4 (NCOA4) acts as a selective cargo receptor that binds to ferritin, a cytoplasmic iron storage complex. By mediating ferritinophagy, NCOA4 regulates iron metabolism and releases free iron in the body, thus playing a crucial role in a variety of biological processes, including growth, development, and metabolism. Recent studies have shown that NCOA4-mediated ferritinophagy is closely associated with the occurrence and development of iron metabolism-related diseases, such as liver fibrosis, renal cell carcinoma, and neurodegenerative diseases. In addition, a number of clinical drugs have been identified to modulate NCOA4-mediated ferritinophagy, significantly affecting disease progression and treatment efficacy. This paper aims to review the current research progress on the role of NCOA4-mediated ferritinophagy in related diseases, in order to provide new ideas for targeted clinical therapy.
Humans ; Nuclear Receptor Coactivators/physiology* ; Ferritins/metabolism* ; Animals ; Neurodegenerative Diseases/metabolism* ; Iron/metabolism* ; Autophagy/physiology* ; Liver Cirrhosis/metabolism* ; Carcinoma, Renal Cell/metabolism* ; Kidney Neoplasms/physiopathology*

Objective To explore the pathogenic mechanisms of Legionella pneumophila(L.pneumophila)infection inhibiting the fusion of endosome-lysosome fusion in mouse macrophages.Methods Twelve C57 mice were randomly divided into control group and L.pneumophila infection group(n=6 each).After anesthesia,an equal volume of physiological saline or L.pneumophila solution was administered nasally.Body weight changes were monitored for 3 consecutive days,and the lungs were extracted to assess injury.Hematoxylin and eosin(HE)staining and immunohistochemical staining were performed to observe the pathological characteristics of lung tissue in both groups.Transcriptome sequencing was utilized to analyze differentially expressed genes(DEGs)and associated signaling pathways in lung tissues.Mouse bone marrow macrophages(BMDMs)were isolated and co-cultured with L.pneumophila,with infection status confirmed by immunofluorescence staining.Transcriptome sequencing was employed to analyze DEGs and enriched related signaling pathways before and after infection.Core genes involved in the post-infection signaling pathway were identified,and the consistency of their mRNA expression levels in vivo and in vitro was verified using RT-qPCR.The expression of relevant proteins was detected by Western Blotting,and bacterial proliferation assays were conducted to evaluate the intracellular replication of L.pneumophila.Results Compared with control group,the body weight of mice in L.pneumophila infection group significantly decreased(P<0.001)on the second and third day post-infection.Edema and red hepatoid degeneration were observed in both left and right lung tissues,with lesion areas spreading from the hilum to the lung periphery.HE staining revealed increased inflammatory cell infiltration in the alveolar spaces,thickening of alveolar septa and increased fibrin exudation in L.pneumophila infection group.Immunohistochemistry results showed a significant increase in myeloperoxidase(MPO)activity in the lung tissue infected mice(P<0.001).Transcriptome sequencing identified 2550 DEGs,with 1444 up-regulated genes and 1106 down-regulated genes.KEGG enrichment analysis indicated that these DEGs were mainly involved in pathways related to tumor necrosis factor,rheumatoid arthritis,Rap1,PI3K-Ak,and phagosome pathways.Immunofluorescence results showed in vitro proliferation of L.pneumophila within mouse BMDMs.Transcriptome sequencing identified 2550 DEGs,including 1677 up-regulated genes and 873 down-regulated genes.KEGG enrichment analysis showed that enrichment in pathway related to transcription dysregulation in cancer,PI3K-Akt and phagosome pathways.Thirteen core genes,including tubulin β1(Tubb1),were identified from the overlap between mouse lung tissue and BMDMs.RT-qPCR results demonstrated a significant decrease in Tubb1 expression in both lung tissue and BMDMs infected with L.pneumophila(P<0.001).Western Blotting results revealed significant decreases in Rab7,Tubb1,and LAMP2 protein expression(P<0.05),and increases in iNOS and MPO expression(P<0.05).Intracellular proliferation experiments indicated that L.pneumophila gradually increased within BMDMs over time.Conclusion The potential mechanism of L.pneumophila infection in mouse macrophages involves the down-regulation of Rab7/Tubb1/LAMP2 which inhibits the endosome-lysosome fusion.

Objective:To establish a detection method for fatty acid composition and methoxylaniline value in pharmaceutical excipient castor oil.Methods:The detection of fatty acid composition involves pre-test of the sam-ple using the methanol sodium methylation method,followed by direct injection analysis using gas chromatography,and finally calculating the content of each fatty acid composition using the area normalization method with correction factors.The detection of methoxylaniline value is achieved by dissolving and diluting the sample with isooctane:isopropanol(8∶2,volume ratio),reacting with 4-methoxylaniline,measuring the absorbance at a wavelength of 350 nm,and calculating the methoxylaniline value.Results:Under the composition of fatty acids,the 8 kinds of fatty acids have good separation degree.The methyl ricinoleate and methyl stearate have good linear relationship in the range of 0.1-5.0 mg·mL-1.The repeatabilityand intermediate precision(RSD)ofthe determination results of each fatty acid in the sample are all less than 5%.It is also found that only α-type of linolenic acid is present in castor oil,without γ-type.In the determination of methoxyaniline value,the blank solvent does not interfere with the determination of the sample,and the repeatability RSD is 3.6%.Conclusion:The detection method for fatty acid composition and meth-oxylaniline value established in this article is accurate and reliable,and can be used for the detection of fatty acid composition and methoxylaniline value in pharmaceutical excipient castor oil.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Diabetic nephropathy(DN)is a serious complication of diabetes mellitus and a leading cause of end-stage renal diseases.In DN patients,key pathological mechanisms include proteinuria,glomerulo-sclerosis,and fibrosis,largely driven by poor glycemic control and oxidative stress caused by prolonged hyperglycemia.This stress damages renal podocytes and triggers inflammatory mesenchymal infiltration of renal tubular cells,exacerbating the progression of proteinuria and fibrosis.Human umbilical cord-de-rived mesenchymal stem cells(hUC-MSCs)offer promising potential for treating DN due to their strong anti-oxidative properties.In this study,we developed a DN mouse model and treated the mouse via tail vein injections of hUC-MSCs(1×106 cells/mouse).The results indicated that hUC-MSCs significantly lowered fasting blood glucose levels(22.5±3.0 vs 14.7±1.1,P＜0.01)and improved glucose toler-ance,as shown by intraperitoneal glucose tolerance test(IPGTT)results(P＜0.05).Additionally,the renal function improved in hUC-MSCs-treated mice,with marked reductions in oxidative stress markers,including blood urea nitrogen(BUN),urinary creatinine(Ucr),urinary protein(PRO),superoxide dismutase(SOD),and malondialdehyde(MDA)(P＜0.05).Histological analyses through hematoxy-lin-eosin(H&E),Periodic Acid-Schiff(PAS),and Sirius red staining demonstrated alleviation of glo-merular mesangial hyperplasia,glomerular hypertrophy,and tubular inflammation.Furthermore,hUC-MSCs treatment downregulated the expression of oxidative stress-related proteins,such as NADPH oxi-dase 4(NOX4)and thioredoxin-interacting protein(TXNIP),and reduced reactive oxygen species(ROS)production(P＜0.05).Meanwhile,human renal cortical proximal tubule epithelial cells(HK-2 cells)were selected for validation in vitro experiments using high glucose treatment followed by super-natants of hUC-MSCs(MSC-CM),and Western blotting showed that the expression of both NOX4 and TXNIP was inhibited(P＜0.05)and ROS expression was reduced.In conclusion,hUC-MSC treatment effectively lowered blood glucose levels and improved renal function in DN mice,likely through the sup-pression of NOX4 expression and TXNIP-mediated oxidative stress.

Objective:To study the surface characterization and bonding strength of zirconia ceramic following nonthermal argon plasma(NTAP)treatment for different times.Methods:Zirconia ceramics were cut into 2 sizes of specimens(Ⅰ:10 mm×10 mm ×2 mm,Ⅱ:3 mm3 mm×2 mm),which were respectively subdivided into 5 groups:blank control group(A),sandblasting group(B)and NTAP treatment for 60,90 and 120 s groups(C,D and E respectively).The changes in surface morphology,roughness,C and O elements and contact angle of the sample surfaces were tested with Type Ⅰ specimens.Type Ⅱ specimens were applied to the uniform surface treatments and were cemented to isolated teeth using the RelyX U200 cement,the samples were submitted to a shear bond strength(SBS)test.Results:SEM and AFM show that NTAP treatment does not alter the surface morphology and roughness of zirconia ceramics.C element decreased and O element increased,and the contact angle became smaller after NTAP treatment.Among the 5 groups,group D showed the most extensive changes.And the result of SBS was as follows of NTAP treat-ment time:0 s＜60 s＜90 s=120 s(among 0,60 and 90 s groups,P＜0.05).Conclusion:NTAP treatment can improve the bond strength of zirconia ceramic by increasing its surface energy and wettability,and NTAP treatment for 90 s may be a suitable surface treatment method for zirconia ceramics.

This consensus was developed by the Orthodontic Society of the Chinese Stomatological Association to provide a systematic, scientific, and practical guideline for informed consent in orthodontic care. Orthodontic treatment is typically lengthy, highly individualized, and involves multiple factors such as growth and development, occlusal function, and facial esthetics. Rapid technological advances and diverse risk profiles make the traditional reliance on orthodontist experience or institutional templates insufficient to ensure patients′ full understanding and autonomous decision-making. To address this, the expert panel conducted extensive reviews of domestic and international guidelines, analyzed representative dispute cases, and performed multicenter patient-clinician surveys. Using a multi-round Delphi method, the group established a standardized informed consent framework covering the initial consultation, treatment, and retention phases. The consensus emphasizes that informed consent is not only a fundamental legal and ethical requirement but also a key step in building trust, improving patient compliance, and enhancing treatment satisfaction. Orthodontists should clearly and comprehensively explain treatment plans, potential risks, uncertainties, and associated costs, while respecting the autonomy of patients or guardians, and maintain continuous communication and dynamic evaluation throughout the treatment process. The release of this consensus provides unified and authoritative guidance for clinical orthodontics, helping to standardize informed consent, enhance its transparency, safeguard patient rights, reduce medical risks, and promote high-quality, sustainable development of orthodontic practice.

Purpose To investigate the correlation between intervertebral disc degeneration and paraspinal muscle fatty infiltration in chronic low back pain(CLBP)using quantitative MRI techniques.Materials and Methods A total of 63 CLBP patients and 42 volunteers in Zigong Fourth People's Hospital from September 2023 to March 2024 were retrospectively collected.Magnetic resonance scans were performed using multi-echo water-fat separation technique and T2 mapping technique.Intervertebral disc degeneration was assessed using the Pfirrmann grading,while paraspinal muscle fatty infiltration was evaluated using the Goutallier grading.Proton density fat fraction(PDFF)of the multifidus and erector spinae muscles,and T2 values of the nucleus pulposus were quantitatively measured.The relationships between these parameters and their associations with age and gender were analyzed.Results Compared with healthy volunteers,CLBP patients showed significantly reduced T2 values of the nucleus pulposusand significantly increased PDFF of the paraspinal muscles(Z=-5.54-4.65,all P<0.001).The Pfirrmann grading of intervertebral discs and the Goutallier grading of paraspinal muscles were significantly correlated with the T2 value of the nucleus pulposus and the PDFF of the paraspinal muscles(|r|>0.4,P<0.05).Age and Pfirrmann grading were independent predictors of paraspinal muscle fat infiltration(β=0.228-5.682,all P<0.001),and gender was also an independent predictor at the L4/5 intervertebral disc level(β=-2.834,-3.352,both P<0.05).Conclusion Intervertebral disc degeneration and paraspinal muscle fat infiltration are closely related in CLBP,age and gender also have an impact.

A retrospective analysis was made on clinical data of a child with osteopathia striata with cranial sclerosis (OS-CS) diagnosed in the Department of Neonatology, Children′s Hospital Affiliated to Shandong University in January 2024.The proband was admitted to hospital due to premature delivery at 30 + 2 weeks, shortness of breath and poor response for 13 days after resuscitation.After birth, the child had no spontaneous breathing with floppy limbs.Tracheal intubation was required for positive pressure ventilation.Cranial ultrasound showed right subventricular hemorrhage with bilateral intraventricular hemorrhage and bilateral parieto-occipital subdural hemorrhage; cardiac ultrasound showed patent ductus arteriosus and tricuspid regurgitation; scrotal ultrasound showed bilateral inguinal cryptorchidism with right testicular hydrocele; gastrointestinal ultrasound showed that the lumen of the transverse colon was filled with many fecal matters with strong echoes.Whole exome sequencing(WES) indicated that the proband carried a hemizygous variant of c. 1489C>T(p.Arg497 *) in the AMER1 gene, which was inherited from his mother, as verified by Sanger sequencing.The hemizygous variant of c. 1489C>T(p.Arg497 *) in the AMER1 gene was rated as likely pathogenic (PVS1+ PM2-Supporting) according to the American College of Medical Genetics and Genomics(ACMG) guidelines, which was not included in the Human Gene Mutation Database(HGMD) database.High-throughput sequencing identified the hemizygous variant of c. 1489C>T(p.Arg497 *) in the AMER1 gene as the genetic etiology of the proband.This was the first report of AMER1 gene variant leading to OS-CS in China.The study enriches the variation spectrum and clinical phenotype spectrum of the AMER1 gene, providing a valuable foundation for clinical diagnosis, treatment, and subsequent research of the disease.

This consensus was developed by the Orthodontic Society of the Chinese Stomatological Association to provide a systematic, scientific, and practical guideline for informed consent in orthodontic care. Orthodontic treatment is typically lengthy, highly individualized, and involves multiple factors such as growth and development, occlusal function, and facial esthetics. Rapid technological advances and diverse risk profiles make the traditional reliance on orthodontist experience or institutional templates insufficient to ensure patients′ full understanding and autonomous decision-making. To address this, the expert panel conducted extensive reviews of domestic and international guidelines, analyzed representative dispute cases, and performed multicenter patient-clinician surveys. Using a multi-round Delphi method, the group established a standardized informed consent framework covering the initial consultation, treatment, and retention phases. The consensus emphasizes that informed consent is not only a fundamental legal and ethical requirement but also a key step in building trust, improving patient compliance, and enhancing treatment satisfaction. Orthodontists should clearly and comprehensively explain treatment plans, potential risks, uncertainties, and associated costs, while respecting the autonomy of patients or guardians, and maintain continuous communication and dynamic evaluation throughout the treatment process. The release of this consensus provides unified and authoritative guidance for clinical orthodontics, helping to standardize informed consent, enhance its transparency, safeguard patient rights, reduce medical risks, and promote high-quality, sustainable development of orthodontic practice.