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*

This study explores the therapeutic differences and mechanisms of salt-processed Phellodendri Chinensis Cortex in improving insulin resistance(IR) based on network pharmacology, molecular docking, and cellular experiments. The components and intersection targets of Phellodendri Chinensis Cortex in improving IR were collected from databases, and a "drug-component-target-disease" network and protein-protein interaction(PPI) network were constructed to screen core components and targets. A total of 29 active components and 240 intersection targets were identified, of which 13 were core targets. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were used to identify key signaling pathways, and molecular docking was performed to validate the binding activity between core components and targets. An IR model in HepG2 cells was induced using insulin combined with high glucose, and the effects of Phellodendri Chinensis Cortex before and after salt-processing on cell glucose consumption were evaluated. The expression of proteins related to the mitogen-activated protein kinase(MAPK) and phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT) signaling pathways was detected by Western blot. The cellular experimental results showed that, compared with the model group, glucose consumption in the drug-treated groups was significantly increased(P<0.01), the phosphorylation level of extracellular regulated protein kinase(ERK) was decreased(P<0.05), the phosphorylation levels of PI3K and AKT were increased, and the expression of glucose transporter 4(GLUT4) was also upregulated(P<0.05). Furthermore, the effect of salt-processed Phellodendri Chinensis Cortex was better than that of raw Phellodendri Chinensis Cortex. The study demonstrates that Phellodendri Chinensis Cortex, both before and after salt-processing, improves IR by regulating the expression of related proteins in the MAPK and PI3K-AKT signaling pathways, with enhanced effects after salt-processing.
Humans ; Network Pharmacology ; Phellodendron/chemistry* ; Insulin Resistance ; Drugs, Chinese Herbal/chemistry* ; Hep G2 Cells ; Signal Transduction/drug effects* ; Molecular Docking Simulation ; Protein Interaction Maps/drug effects* ; Proto-Oncogene Proteins c-akt/genetics* ; Phosphatidylinositol 3-Kinases/genetics* ; Glucose/metabolism*

Bronchiectasis(BE) is the third major chronic airway disease, and its incidence rate shows a continuously increasing trend. Bronchiectasis is a highly heterogeneous chronic airway disease. Due to structural alterations, airflow limitation, and mucus hypersecretion, clinical treatment faces many challenges. Particularly, problems including Pseudomonas aeruginosa-dominant drug-resistant bacterial colonization, recurrent infections, airway mucus hypersecretion, and impaired lung function are the most urgent, requiring long-term and personalized treatment and management integrating traditional Chinese and western medicine to prevent the recurrence and continuous progression of the disease. In recent years, both traditional Chinese medicine and western medicine have made certain progress in pathogenesis theories, clinical studies, and basic research regarding the therapeutic challenges of bronchiectasis. Therefore, this paper summarized relevant research from the past 10 years and explored future directions and potential advantages of integrated traditional Chinese and western medicine treatment, providing references for optimizing the clinical management strategies for bronchiectasis.
Bronchiectasis/drug therapy* ; Humans ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional/methods* ; Animals

In this study,an ON/OFF type micro-valve with a sandwich(glass-silicon-glass)structure was designed and fabricated based on the micro-electro-mechanical system(MEMS)technique.The deformable membrane of this micro-valve was prepared on the silicon on insulator(SOI)substrate and sealed using Si-Si bonding and anodic bonding methods.The micro-valve had high-temperature stability and was suitable for integration with other gas chromatography components.The deformable membrane with a thickness of 10 μm was processed on the top silicon of the SOI substrate.The flow control of the micro-valve could be achieved by changing the driving pressure applied to the deformable membrane to deform it.Compared with polymer membranes,the deformable membrane prepared on the top layer silicon of SOI had better temperature stability and could be released using the deep reactive ion etching technique after silicon-silicon bonding,avoiding deformation during the preparation process.In addition,due to the small gap between the membrane and the inlet/outlet holes,the dead volume of the microvalve was very small.The test results indicated that the micro-valve achieved flow control and ON/OFF functions with good repeatability.

In this work,with tris(4-aminophenyl)amine(TAPA)and 1,3,5-tris(4-formylphenyl)benzene(TFPB)as monomers,an imine-type porous organic polymer,TAPA-TFPB,was synthesized using a simple method under the catalysis of acetic acid.The material TAPA-TFPB was used as solid-phase extraction adsorbent and combined with ultra-performance liquid chromatography/quadrupole time-of-flight-tandem mass spectrometry(UHPLC-QTOF-MS)to establish a detection method for four kinds of nitrofuran metabolites(NFMs)residues in meat samples.The parameters of the adsorbent dosage,the pH value and volume of sample,and the type and volume of washing and eluent solvents were optimized,respectively.Under the optimal extraction conditions,low detection limits(0.11-1.60 μg/kg)were achieved for four kinds of NFMs.At three different spiked levels,the intra-day and inter-day precisions(Relative standard deviations)were 2.8% -10.9% and 4.3% -16.2%,respectively,and the spiked recoveries were 72.0% -107.2%.The results showed that the method chould be used for efficient extraction and analysis of trace NFMs residues in meat samples,indicating that TAPA-TFPB was a kind of promising SPE adsorbent.

A monolithic integrated gas chromatography chip,consisting of a micro gas chromatography column(μGCC)and a micro helium discharge ionization detector(μHDID)was proposed.The chip was fabricated using micro electromechanical system(MEMS)technique,and its sensitivity was improved from two aspects.On one hand,open tubular column was selected as the separation device,and the auxiliary helium channel width of μHDID was modulated based on the microchannel width of the μGCC to match the flow rates of μHDID and μGCC.On the other hand,the electrode structure inside the μHDID collection zone was optimized,a bias electrode group around the collection electrode was constructed,and the ion collection efficiency was improved.After coating HKUST-1 as the stationary phase,the monolithic integrated gas chromatography chip could achieve baseline separation and detection of light hydrocarbon gas mixture(methane,ethane,propane,andn-butane),with a detection limit for propane as low as 25 pg.The chip could carried out test under temperature-programmed conditions,with a resolution of 9.24 for ethane and propane.

A micro gas chromatographic column with mesoporous surface micro column array prepared by anodization method was proposed.A porous support layer with a characteristic pore size of about 30 nm inside the chromatographic column was prepared in situ using anodization method,and a uniform alumina stationary phase was deposited on the mesoporous support layer using atom layer deposition(ALD)technique.The existence of a mesoporous support layer increased surface area of the chromatographic column,thereby increasing the total amount of stationary phase loading and enhancing column capacity,which facilitated chromatographic separation.The test results showed that the porous support layer significantly reduced the longitudinal molecular diffusion and mass transfer resistance of the micro gas chromatographic column,and significantly increased the number of theoretical plates(n-nonane increased by 290.2%).Furthermore,column efficiency of the chromatographic column was less affected by flow rate,which was conducive to rapid separation of heavy hydrocarbon mixtures.

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 analyze the predictive value of the serum amyloid A/C-reactive protein ratio(SAA/CRP),lactate dehydrogenase(LDH),and chitinase-40(YKL-40)combined with conventional influencing factors for the prognosis of children with refractory mycoplasmal pneumonia(RMPP).Methods A retrospective study was conducted on 180 children with RMPP admitted to the First People's Hospital of Nanyang from January to December 2023,serving as study group,and 90 children with general mycoplasmal pneumonia(GMPP)as control group.The clinical data of the two groups,including age,gender,and serum levels of SAA/CRP,LDH,and YKL-40,were compared.On the day of admission,the disease severity of the children in study group was assessed and divided into mild(n=102)and severe(n=78)groups.After treatment,they were further categorized into poor prognosis(n=52)and good prognosis(n=128)groups based on the occurrence of adverse events.The levels of serum SAA/CRP,LDH,and YKL-40 were compared between mild-case and severe-case children in study group,as well as between children with good and poor prognosis.A binary logistic regression model was used to analyze the influencing factors for poor prognosis in children with RMPP.Receiver operating characteristic(ROC)curve was used to evaluate the predictive value of serum SAA/CRP,LDH,and YKL-40 for the prognosis of children with RMPP.Conventional influencing factors[disease severity,oxygen therapy duration,pneumonia severity index(PSI)score,and acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)score]were used as the conventional prediction scheme,and the conventional prediction scheme combined with the levels of serum SAA/CRP,LDH,and YKL-40 was used as the new prediction scheme.The predictive values of the two prediction schemes for the prognosis of children with RMPP were compared.Results The levels of serum SAA/CRP,LDH,and YKL-40 in study group were higher than those in control group(P＜0.05),and the levels of serum SAA/CRP,LDH,and YKL-40 in children with severe RMPP were higher than those in children with mild RMPP(P＜0.05).In study group,the proportion of children with pleural effusion,the proportion of severe-case disease severity,oxygen therapy duration,PSI score,APACHE Ⅱ score,and the levels of serum SAA/CRP,LDH,and YKL-40 in children with poor prognosis were higher than those in children with good prognosis(P＜0.05).Binary logistic regression analysis showed that disease severity,oxygen therapy duration,PSI score,APACHE Ⅱ score,and the levels of serum SAA/CRP,LDH,and YKL-40 were all factors affecting poor prognosis in children with RMPP(P＜0.05).The areas under the curves(AUCs)of serum SAA/CRP,LDH,and YKL-40 for predicting the prognosis of children with RMPP were 0.756,0.749,and 0.734,respectively.The AUC of the new prediction scheme was 0.945,which was significantly higher than that of the conventional prediction scheme(AUC=0.859),with a statistically significant difference(P=0.011).Conclusion Serum SAA/CRP,LDH,and YKL-40 levels combined with the conventional prediction scheme have a high predictive efficacy for the prognosis of children with RMPP.

With the rapid development of competitive sports, the incidence of anterior cruciate ligament (ACL) injury is on the rise. Such injuries may shorten athletes′ career and lead to other long-term adverse consequences. Although athletes generally recover well after ACL reconstruction, many still struggle to return to their pre-injury performance levels. Advances in the understanding of ACL anatomy and injury mechanisms, along with the evolution of surgical techniques and rehabilitation methods, have provided more individualized and tailored options for athletes following ACL injuries. However, there is currently no consensus in China regarding surgical and rehabilitation strategies for competitive athletes aiming to return to sports after ACL injuries. To this end, the Sports Medicine Committee of the Chinese Research Hospital Association and the Editorial Board of the Chinese Journal of Trauma jointly formulated the Expert consensus on surgical treatment and rehabilitation for competitive sports athletes returning to sports after anterior cruciate ligament injury ( version 2025), and presented 14 recommendations covering surgical indications, preoperative rehabilitation, surgical timing, surgical strategies and postoperative rehabilitation strategies, aiming to improve the surgical treatment and rehabilitation system for ACL injuries in competitive athletes and facilitate their return to high-level sports performance after injury.