Development of machine learning-based personalized predictive models for risk evaluation of hepatocellular carcinoma in hepatitis B virus-related cirrhosis patients with low levels of serum alpha-fetoprotein.

INTRODUCTION AND OBJECTIVES: The increasing incidence of hepatocellular carcinoma (HCC) in China is an urgent issue, necessitating early diagnosis and treatment. This study aimed to develop personalized predictive models by combining machine learning (ML) technology with a demographic, medical history, and noninvasive biomarker data. These models can enhance the decision-making capabilities of physicians for HCC in hepatitis B virus (HBV)-related cirrhosis patients with low serum alpha-fetoprotein (AFP) levels. PATIENTS AND METHODS: A total of 6,980 patients treated between January 2012 and December 2018 were included. Pre-treatment laboratory tests and clinical data were obtained. The significant risk factors for HCC were identified, and the relative risk of each variable affecting its diagnosis was calculated using ML and univariate regression analysis. The data set was then randomly partitioned into validation (20%) and training sets (80%) to develop the ML models. RESULTS: Twelve independent risk factors for HCC were identified using Gaussian naïve Bayes, extreme gradient boosting (XGBoost), random forest, and least absolute shrinkage and selection operation regression models. Multivariate analysis revealed that male sex, age >60 years, alkaline phosphate >150 U/L, AFP >25 ng/mL, carcinoembryonic antigen >5 ng/mL, and fibrinogen >4 g/L were the risk factors, whereas hypertension, calcium <2.25 mmol/L, potassium ≤3.5 mmol/L, direct bilirubin >6.8 µmol/L, hemoglobin <110 g/L, and glutamic-pyruvic transaminase >40 U/L were the protective factors in HCC patients. Based on these factors, a nomogram was constructed, showing an area under the curve (AUC) of 0.746 (sensitivity=0.710, specificity=0.646), which was significantly higher than AFP AUC of 0.658 (sensitivity=0.462, specificity=0.766). Compared with several ML algorithms, the XGBoost model had an AUC of 0.832 (sensitivity=0.745, specificity=0.766) and an independent validation AUC of 0.829 (sensitivity=0.766, specificity=0.737), making it the top-performing model in both sets. The external validation results have proven the accuracy of the XGBoost model. CONCLUSIONS: The proposed XGBoost demonstrated a promising ability for individualized prediction of HCC in HBV-related cirrhosis patients with low-level AFP.

[Identification and expression pattern analysis of Trihelix transcription factor family genes of ginseng].

The function of the Trihelix transcription factor is that it plays an important role in many abiotic stresses, especially in the signaling pathway of low temperature, drought, flood, saline, abscisic acid, methyl jasmonate, and other abiotic stresses. However, there are few studies on the Trihelix gene family of ginseng. In this study, 41 Trihelix gene family members were identified and screened from the ginseng genome database, and their physicochemical properties, cis-acting elements, subcellular localization, chromosomal assignment, and abiotic stress-induced expression patterns were analyzed by bioinformatics methods. The results showed that 85% of Trihelix family members of ginseng were located in the nucleus, and the main secondary structure of Trihelix protein was random coil and α helix. In the promoter region of Trihelix, cis-acting regulatory elements related to various abiotic stresses such as low temperature, hormone response, and growth and development were identified. Through the collinearity analysis of interspecific Trihelix transcription factors of model plants Arabidopsis thaliana and ginseng, 19 collinear gene pairs were found between A. thaliana and ginseng, and no collinear gene pairs existed on chromosomes 3, 6, and 12 only. qRT-PCR analysis showed that the expression of GWHGBEIJ010320.1 was significantly up-regulated under low temperature stress, a significant response to low temperature stress. This study lays a foundation for further research on the role of the Trihelix transcription factor of ginseng in abiotic stress, as well as the growth and development of ginseng.

Retinal thickness and microvascular alterations observed by optical coherence tomography in antineutrophil cytoplasmic antibody-associated vasculitis: a cross-sectional study.

Background: As an autoimmune disease, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) often affects multiple organs, including the ocular system. This study aims to investigate differences in retinal thickness (RT) and retinal superficial vascular density (SVD) between patients with AAV and healthy controls (HCs) using optical coherence tomography angiography (OCTA). Currently, these differences are not clear. Methods: A total of 16 AAV individuals (32 eyes) and 16 HCs (32 eyes) were recruited to this cross-sectional study conducted in the First Affiliated Hospital of Nanchang University from June 2023 to September 2023. The study protocol conformed with the tenets of the Declaration of Helsinki (as revised in 2013). Each image observed by OCTA was divided into 9 regions using the Early Treatment Diabetic Retinopathy Study (ETDRS) subzones as a guide. Results: In the full layer, the RT of AAV patients was found to be significantly reduced in the inner superior (IS, P<0.001), outer superior (OS, P=0.003), inner temporal (IT, P=0.003), and outer temporal (OT, P<0.001) regions; inner RT was significantly lower in the IS (P=0.006), OS (P<0.001), inner nasal (IN, P=0.005), outer nasal (ON, P<0.001), and center (C, P=0.01) regions than that in HCs. Outer RT of AAV patients showed a reduction in the IS (P<0.001), as well as IT (P=0.008), and OT (P<0.001) regions. No statistically significant differences were seen in the different subregions in other different layers (P>0.05). Only the inner inferior (II) and outer inferior (OI) regions of SVD in AAV patients did not differ significantly from controls. All other regions showed a reduction in SVD. The details are as follows: IS (P<0.001), OS (P<0.001), IT (P=0.005), OT (P<0.001), IN (P<0.001), ON (P<0.001), and C (P=0.003). According to receiver operating characteristic (ROC) curve analysis, the full IS region [area under the curve (AUC): 0.8892, 95% confidence interval (CI): 0.8041-0.9742, P<0.001] had the highest diagnostic value for AAV-induced reduction in RT. The IS (AUC: 0.9121, 95% CI: 0.8322-0.9920, P<0.001) region was also the most sensitive to changes in SVD of AAV individuals. In addition, we found that SVD in the IN region (r=-0.4224, 95% CI: -0.6779 to -0.0757, P=0.02) as well as mean visual acuity (r=-0.3922, 95% CI: -0.6579 to -0.0397, P=0.03) of AAV patients were negatively correlated with disease duration. However, we did not find an association between SVD and RT in this study. Conclusions: The findings from OCTA indicated a reduction in RT and SVD among patients with AAV. OCTA allows for the evaluation of AAV-related ocular lesions and holds promise for monitoring of disease progression through regular evaluations.

Effects of polystyrene microspheres on the swimming behavior and metabolism of grass carp (Ctenopharyngodon idella).

Microplastics (MPs) are a heterogeneous class of pollutants fouling aquatic environments and they are hazardous to aquatic organisms. This study investigated the size-dependent effects of polystyrene microspheres (PSMPs) on the swimming ability, metabolism, and oxidative stress of juvenile grass carp (Ctenopharyngodon idella). Test fish were exposed to four sizes of PSMPs (0.07, 0.5, 5, and 20-µm), and swimming ability was tested after different exposure times (2, 7, and 15 days). To measure the effect on swimming ability, critical swimming speed (Ucrit) was determined, and to assess metabolic effects, oxygen consumption (MO2), routine metabolic rate (RMR), maximum oxygen consumption (MMR), and excess post-exercise oxygen consumption (EPOC) were determined. To assess the effects on oxidative stress, the activities of two antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT) were determined in the liver and gills of test fish. After exposure to 20 µm PSMPs, there was a significant drop in Ucrit compared to the control group (P<0.05), with decreases of 22 % on Day 2 and Day 7, and 21 % on Day 15. The RMR and MMR increased significantly (P<0.05), the RMR by 23.9 % on Day 2 and the MMR by 17.2 % on Day 2 and on Day 15, 44.7 % and 20.0 % respectively. The EPOC decreased with exposure time, by 31 % (0.07-µm), 45 %-(0.5-µm), 49 % (5-µm), and 57 % (20-µm) after 15 days. Exposure to the larger PSMPs increased CAT and SOD activity more than the smaller PSMPs and the increases began with SOD activity in the gills. The larger PSMPs were consistently more harmful to juvenile grass carp than the smaller PSMPs. Our results clearly show that PSMPs have detrimental effects on juvenile grass carp and provide additional scientific evidence that environmental monitoring and regulation of microplastic pollution is necessary.

Stromal lenticule addition keratoplasty with corneal crosslinking for corneal ectasia secondary to FS-LASIK: a case series.

AIM: To explore the clinical efficacy and safety of stromal lenticule addition keratoplasty (SLAK) with corneal crosslinking (CXL) on patients with corneal ectasia secondary to femtosecond laser-assisted in situ keratomileusis (FS-LASIK). METHODS: A series of 5 patients undertaking SLAK with CXL for the treatment of corneal ectasia secondary to FS-LASIK were followed for 4-9mo. The lenticules were collected from patients undertaking small incision lenticule extraction (SMILE) for the correction of myopia. Adding a stromal lenticule was aimed at improving the corneal thickness for the safe application of crosslinking and compensating for the thin cornea to improve its mechanical strength. RESULTS: All surgeries were conducted successfully with no significant complications. Their best corrected visual acuity (BCVA) ranged from 0.05 to 0.8-2 before surgery. The pre-operational total corneal thickness ranged from 345-404 µm and maximum keratometry (Kmax) ranged from 50.8 to 86.3. After the combination surgery, both the corneal keratometry (range 55.9 to 92.8) and total corneal thickness (range 413-482 µm) significantly increased. Four out of 5 patients had improvement of corneal biomechanical parameters (reflected by stiffness parameter A1 in Corvis ST). However, 3 patients showed decreased BCVA after surgery due to the development of irregular astigmatism and transient haze. Despite the onset of corneal edema right after SLAK, the corneal topography and thickness generally stabilized after 3mo. CONCLUSION: SLAK with CXL is a potentially beneficial and safe therapy for advanced corneal ectasia. Future work needs to address the poor predictability of corneal refractometry and compare the outcomes of different surgical modes.

Convergence in simulating global soil organic carbon by structurally different models after data assimilation.

Current biogeochemical models produce carbon-climate feedback projections with large uncertainties, often attributed to their structural differences when simulating soil organic carbon (SOC) dynamics worldwide. However, choices of model parameter values that quantify the strength and represent properties of different soil carbon cycle processes could also contribute to model simulation uncertainties. Here, we demonstrate the critical role of using common observational data in reducing model uncertainty in estimates of global SOC storage. Two structurally different models featuring distinctive carbon pools, decomposition kinetics, and carbon transfer pathways simulate opposite global SOC distributions with their customary parameter values yet converge to similar results after being informed by the same global SOC database using a data assimilation approach. The converged spatial SOC simulations result from similar simulations in key model components such as carbon transfer efficiency, baseline decomposition rate, and environmental effects on carbon fluxes by these two models after data assimilation. Moreover, data assimilation results suggest equally effective simulations of SOC using models following either first-order or Michaelis-Menten kinetics at the global scale. Nevertheless, a wider range of data with high-quality control and assurance are needed to further constrain SOC dynamics simulations and reduce unconstrained parameters. New sets of data, such as microbial genomics-function relationships, may also suggest novel structures to account for in future model development. Overall, our results highlight the importance of observational data in informing model development and constraining model predictions.

(±)-hypermonanones A-G, seven pairs of monoterpenoid polyprenylated acylphloroglucinol enantiomers from Hypericum monanthemum.

Seven pairs of undescribed monoterpenoid polyprenylated acylphloroglucinol enantiomers [(±)-hypermonanones A-G (1-7)], together with three known analogues, were identified from the whole plant of Hypericum monanthemum Hook. The structures of these compounds were determined by analyses of their UV, HRESIMS, 1D/2D NMR spectroscopic data, and NMR calculations. The absolute configurations of these compounds were assigned by ECD calculations after chiral HPLC separation. Diverse monoterpene moieties were fused at C-3/C-4 of the dearomatized acylphloroglucinol core, which led to 3,4-dihydro-2H-pyran-integrated angular or linear type 6/6/6 tricyclic skeletons in 1-7. Compounds (-)-2 and (+)-2 exhibited significant NO inhibitory activity against LPS induced RAW264.7 cells with the IC50 values of 7.07 ± 1.02 µM and 11.39 ± 0.24 µM, respectively.

Garciyunnanones A-R: Caged polycyclic polyprenylated acylphloroglucinols decorated with a lavandulyl substituent from Garcinia yunnanensis.

Garciyunnanones A-R (1-18), eighteen undescribed caged polycyclic polyprenylated acylphloroglucinols, two undescribed biogenetic congeners (19-20), and nineteen known analogues (21-39), were isolated from the stem barks of Garcinia yunnanensis Hu. All of these isolates are decorated with a C-5 lavandulyl substituent. Their structures and absolute configurations were confirmed by HRESIMS, 1D & 2D NMR spectroscopic analysis, quantum chemical calculations of electronic circular dichroism data, and single-crystal X-ray diffraction analysis. The X-ray crystallographic data of ten isolated caged compounds ascertained the absolute configuration of C-23 in the lavandulyl as S. The cytotoxicity on three cancer cell lines and the anti-nonalcoholic steatohepatitis activity of the isolates were tested. In a free fatty acid-induced L02 cell model, compounds 33 and 39 decreased intracellular lipid accumulation significantly.

Unraveling the Contribution of MulSOS2 in Conferring Salinity Tolerance in Mulberry (Morus atropurpurea Roxb).

Salinity is one of the most serious threats to sustainable agriculture. The Salt Overly Sensitive (SOS) signaling pathway plays an important role in salinity tolerance in plants, and the SOS2 gene plays a critical role in this pathway. Mulberry not only has important economic value but also is an important ecological tree species; however, the roles of the SOS2 gene associated with salt stress have not been reported in mulberry. To gain insight into the response of mulberry to salt stress, SOS2 (designated MulSOS2) was cloned from mulberry (Morus atropurpurea Roxb), and sequence analysis of the amino acids of MulSOS2 showed that it shares some conserved domains with its homologs from other plant species. Our data showed that the MulSOS2 gene was expressed at different levels in different tissues of mulberry, and its expression was induced substantially not only by NaCl but also by ABA. In addition, MulSOS2 was exogenously expressed in Arabidopsis, and the results showed that under salt stress, transgenic MulSOS2 plants accumulated more proline and less malondialdehyde than the wild-type plants and exhibited increased tolerance to salt stress. Moreover, the MulSOS2 gene was transiently overexpressed in mulberry leaves and stably overexpressed in the hairy roots, and similar results were obtained for resistance to salt stress in transgenic mulberry plants. Taken together, the results of this study are helpful to further explore the function of the MulSOS2 gene, which provides a valuable gene for the genetic breeding of salt tolerance in mulberry.

Noninvasive prenatal testing for the detection of fetal chromosome 17 microduplication: clinical implications and findings.

BACKGROUND:  Noninvasive prenatal testing (NIPT) is widely used to screen for fetal aneuploidies. However, there are few reports of using NIPT for screening chromosomal microduplications and microdeletions. This study aimed to investigate the application efficiency of NIPT for detecting chromosomal microduplications. METHODS: Four cases of copy number gains on the long arm of chromosome 17 (17q12) were detected using NIPT and further confirmed using copy number variation (CNV) analysis based on chromosome microarray analysis (CMA). RESULTS: The prenatal diagnosis CMA results of the three cases showed that the microduplications in 17q12 (ranging from 1.5 to 1.9 Mb) were consistent with the NIPT results. The karyotypic analysis excluded other possible unbalanced rearrangements. The positive predictive value of NIPT for detecting chromosomal 17q12 microduplication was 75.0%. CONCLUSIONS:  NIPT has a good screening effect on 17q12 syndrome through prenatal diagnosis, therefore it could be considered for screening fetal CNV during the second trimester. With the clinical application of NIPT, invasive prenatal diagnoses could be effectively reduced while also improving the detection rate of fetal CNV.

Size, distribution, and vulnerability of the global soil inorganic carbon.

Global estimates of the size, distribution, and vulnerability of soil inorganic carbon (SIC) remain largely unquantified. By compiling 223,593 field-based measurements and developing machine-learning models, we report that global soils store 2305 ± 636 (±1 SD) billion tonnes of carbon as SIC over the top 2-meter depth. Under future scenarios, soil acidification associated with nitrogen additions to terrestrial ecosystems will reduce global SIC (0.3 meters) up to 23 billion tonnes of carbon over the next 30 years, with India and China being the most affected. Our synthesis of present-day land-water carbon inventories and inland-water carbonate chemistry reveals that at least 1.13 ± 0.33 billion tonnes of inorganic carbon is lost to inland-waters through soils annually, resulting in large but overlooked impacts on atmospheric and hydrospheric carbon dynamics.

The crosstalk between mitochondrial quality control and metal-dependent cell death.

Mitochondria are the centers of energy and material metabolism, and they also serve as the storage and dispatch hubs of metal ions. Damage to mitochondrial structure and function can cause abnormal levels and distribution of metal ions, leading to cell dysfunction and even death. For a long time, mitochondrial quality control pathways such as mitochondrial dynamics and mitophagy have been considered to inhibit metal-induced cell death. However, with the discovery of new metal-dependent cell death including ferroptosis and cuproptosis, increasing evidence shows that there is a complex relationship between mitochondrial quality control and metal-dependent cell death. This article reviews the latest research results and mechanisms of crosstalk between mitochondrial quality control and metal-dependent cell death in recent years, as well as their involvement in neurodegenerative diseases, tumors and other diseases, in order to provide new ideas for the research and treatment of related diseases.

Long-term observation of V4c implantable collamer lenses implantation for moderate to extreme high myopia correction: five years follow-up.

BACKGROUND: This study aims to assess the long term effectiveness, safety, predictability and stability of V4c implantable collamer lenses (ICL) for correction of moderate to extreme high myopia. METHODS: We reviewed 125 eyes from 64 patients who implanted V4c ICL at the Refractive Surgery Center of West China Hospital in Chengdu, China, between May 2015 and January 2017. The median spherical equivalent was -11.50 D (interquartile range [IQR]: -13.00 to -9.00 D). We followed up with the patients over five years and evaluated several parameters, including uncorrected visual acuity (UDVA), corrected visual acuity (CDVA), axial length, refractive error, endothelial cell density (ECD), intraocular pressure (IOP), white-to-white distance (WTW), and vault. We performed a correlation analysis to explore the potential impacts on vault following implantation. RESULTS: The median safety index (postoperative CDVA/preoperative CDVA) during the last follow-up was 1.00 (interquartile range [IQR]: 1.00-1.20), and the efficacy indices (postoperative UDVA/preoperative CDVA) were 1.20 (IQR: 1.00-1.25), 1.20 (IQR: 1.00-1.33), and 0.8 (IQR: 0.65-1.00) at postoperative 1 week, 1 month, and 5 years, respectively. At the five-year mark, 16% of the eyes were within ±0.50 D of expected correction, and 73% were within ±2.00 D. No significant difference in ECD was observed between pre-operative and post-operative measurements. Compared to baseline, we observed a significant increase in IOP at the one-week follow-up, which decreased significantly at the one-month visit. Furthermore, we identified ICL size and spherical equivalent (SE) as independent variables in a multiple linear regression model that accurately predicted the five-year vault after surgery. CONCLUSION: In conclusion, V4c ICL implantation is an effective and safe treatment for moderate to extreme high myopia with good predictability and stability over the long-term.

Tumor-infiltrating macrophage associated lncRNA signature in cutaneous melanoma: implications for diagnosis, prognosis, and immunotherapy.

Along with the increasing knowledge of long noncoding RNA, the interaction between the long noncoding RNA (lncRNA) and tumor immune infiltration is increasingly valued. However, there is a lack of understanding of correlation between regulation of specific lncRNAs and tumor-infiltrating macrophages within melanoma. In this research, a macrophage associated lncRNA signature was identified by multiple machine learning algorithms and the robust and effectiveness of signature also validated in other independent datasets. The signature contained six specific lncRNAs (PART1, LINC00968, LINC00954, LINC00944, LINC00518 and C20orf197) was constructed, which could diagnose melanoma and predict the prognosis of patients. Moreover, our signature achieves higher accuracy than the previous well-established markers and regarded as an independent prognostic indicator. The pathway enrichment revealed that these lncRNAs were closely correlated with many immune processes. In addition, the signature was associated with different immune microenvironment and applied to predict response of immune checkpoint inhibitor therapy (low risk of patients well respond to anti-PD-1 therapy and high risk is insensitive to anti-CTLA-4 therapy). Therefore, our finding supplies a more accuracy and effective lncRNA signature for tumor-infiltrating macrophages targeting treatment approaches and affords a new clinical application for predicting the response of immunotherapies in melanomas.

Application of three-dimensional material CZIF-8/CS-MS as adsorbents for the determination of plant growth regulators in Schisandra chinensis.

In this study, we employed a melamine sponge (MS) as the skeleton material and utilized carbonized ZIF-8 (CZIF-8) and chitosan (CS) as the raw materials to prepare CZIF-8/CS-MS, a novel material featuring a three-dimensional interconnected porous network. The resulting CZIF-8/CS-MS material possesses a unique porous structure, significant specific surface area and abundant active sites. These characteristics make CZIF-8/CS-MS a promising absorbent for selective purification of plant growth regulators (PGRs) including 1-naphthlcetic acid (NAA), naphthoxyacetic acid (NOA), 4-chlorophenoxyacetic acid (4-CPA), 2,4-dichlorophenoxyacetic acid (2,4-D). After optimizing the extraction conditions, excellent linearity (r > 0.9994) was observed within a wide linear range of 1-100 ng/mL using ultra high performance liquid chromatography-tandem quadrupole mass spectrometry. The detection limits (LODs) and limits of quantification (LOQs) were found to be in the range of 0.013-0.154 ng/mL and 0.044-0.515 ng/mL, respectively. Additionally, the relative recovery of Schisandra chinensis fruit samples was determined to be 89.7-99.4 %, with a relative standard deviation (RSDs) of ≤ 8.4 % (n = 3). Compared to other methods, this approach offers a multitude of benefits, which include but are not limited to exceptional sensitivity, reduced sample volume requirements, low LODs, a comparable linear range, and high reproducibility. The findings of this study pave the way for exploring novel functionalized sponge columns, which leverage the integration of nano-sorbent materials and coating agents, for the purpose of analyzing PGRs within intricate matrix samples.

Ocular microvascular alteration in patients with myocardial infarction-a new OCTA study.

Myocardial infarction is defined as a sudden decrease or interruption in blood flow to the coronary arteries, causing ischemic necrosis of the corresponding cardiomyocytes. It is unclear whether systemic macrovascular alterations are associated with retinal microvascular changes. This study utilized optical coherence tomography angiography (OCTA) to compare variations in conjunctival vascular density and fundus retinal vessel density between patients with myocardial infarction (MI) and healthy controls. This study recruited 16 patients (32 eyes) with MI and 16 healthy controls (32 eyes). The superficial retinal layer (SRL), deep retinal layer (DRL) and conjunctival capillary plexus in each eye were evaluated by OCTA. Parameters measured included the density of the temporal conjunctival capillary, retinal microvascular (MIR) and macrovascular (MAR) alterations and total MIR (TMI). The microvascular density of each retinal region was evaluated by the hemisphere segmentation (SR, SL, IL, and IR), annular partition (C1, C2, C3, C4, C5 and C6), and modified early treatment of diabetic retinopathy study (R, S, L, and I) methods. In the macular area, the superficial and deep retinal microvascular densities displayed notable variations. In the superficial layers, the superficial TMI, superficial MIR, and superficial MAR, as well as densities in the SL, IL, S, L, C1, C2, C5 and C6 regions, were significantly lower in MI patients (p < 0.05 each). In the deep layers, the deep MIR and deep TMI), as well as densities in the SL, IL, L, C1, C2 and C6 regions were significantly lower in MI patients (p < 0.05 each). In contrast, the conjunctival microvascular density was significantly higher in MI patients than in healthy controls (p < 0.001). The microvascular densities measured in the deep and superficial retinal layers and in the conjunctiva differ in MI patients and healthy controls. OCTA is effective in detecting changes in the ocular microcirculation.

Ferritinophagy: A novel insight into the double-edged sword in ferritinophagy-ferroptosis axis and human diseases.

Nuclear receptor coactive 4 (NCOA4), which functions as a selective cargo receptor, is a critical regulator of the particularly autophagic degradation of ferritin, a process known as ferritinophagy. Mechanistically, NCOA4-mediated ferritinophagy performs an increasingly vital role in the maintenance of intracellular iron homeostasis by promoting ferritin transport and iron release as needed. Ferritinophagy is not only involved in iron-dependent responses but also in the pathogenesis and progression of various human diseases, including metabolism-related, neurodegenerative, cardiovascular and infectious diseases. Therefore, ferritinophagy is of great importance in maintaining cell viability and function and represents a potential therapeutic target. Recent studies indicated that ferritinophagy regulates the signalling pathway associated with ferroptosis, a newly discovered type of cell death characterised by iron-dependent lipid peroxidation. Although accumulating evidence clearly demonstrates the importance of the interplay between dysfunction in iron metabolism and ferroptosis, a deeper understanding of the double-edged sword effect of ferritinophagy in ferroptosis has remained elusive. Details of the mechanisms underlying the ferritinophagy-ferroptosis axis in regulating relevant human diseases remain to be elucidated. In this review, we discuss the latest research findings regarding the mechanisms that regulate the biological function of NCOA4-mediated ferritinophagy and its contribution to the pathophysiology of ferroptosis. The important role of the ferritinophagy-ferroptosis axis in human diseases will be discussed in detail, highlighting the great potential of targeting ferritinophagy in the treatment of diseases.