Hepatitis B virus reactivation in hepatocellular carcinoma patients after hepatic arterial infusion chemotherapy combined with and without immunotherapy.

BACKGROUND: Hepatitis B virus (HBV) reactivation (HBVr) is a major concern for hepatocellular carcinoma (HCC) patients undergoing hepatic arterial infusion chemotherapy (HAIC) using mFOLFOX6 regimen. There is insufficient evidence to support the routine use of HAIC combined with immunotherapy in HCC patients with HBVr. The aim of this study was to examine the adverse events (AEs) related to HBVr in HCC patients after HAIC, with or without immunotherapy, and to assess the effectiveness of antiviral prophylaxis for HBVr. METHODS: Medical records of HCC patients receiving HAIC combined with and without immunotherapy between January 2021 and June 2023 were reviewed. The patients were divided into two groups based on whether they received immunotherapy or not. RESULTS: Out of the 106 patients, 32 (30.2%) developed HBVr. Among these, 23 eligible patients with HBVr were included, with 14 patients (61%) receiving immunotherapy and nine patients (39%) not receiving immunotherapy. Prior to HAIC treatment, four patients in each group had detectable HBV DNA with median titre of 3.66 × 102 IU/ml (patients with immunotherapy) and 1.98 × 102 IU/ml (patients without immunotherapy), respectively. Fifteen patients did not show detectable HBV DNA. At HBVr occurrence, the median HBV DNA level was 6.95 × 102 IU/ml for all patients, 4.82 × 102 IU/ml in patients receiving immunotherapy and 1.3 × 103 IU/ml in patients not receiving immunotherapy. Grade 3 hepatitis developed in 12 cases of all patients (12/23, 48%), including five patients with immunotherapy (56%) and seven patients without immunotherapy (78%). At the 3-month follow-up, HBV DNA was detected in 10 patients, with a median HBV DNA level of 2.05 × 102 IU/ml (range, 1.5 × 102- 3.55 × 102 IU/ml) in patients (7/10) with immunotherapy and 4.28 × 102 IU/ml (range, 1.15 × 102- 5.88 × 102 IU/ml) in patients (3/10) without immunotherapy. Intensified antiviral treatment was administered to all patients. No HBVr-related fatal events occurred. CONCLUSION: HBVr can occur after HAIC combined with or without immunotherapy. The degree of liver damage did not differ significantly in patients treated with or without immunotherapy. Intensified antiviral treatment was found to be crucial for HCC patients with HBVr.

Sorafenib plus TACE with or without camrelizumab for the treatment of intermediate and advanced hepatocellular carcinoma.

OBJECTIVES: To compare the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with sorafenib and camrelizumab or with sorafenib alone in patients with intermediate or advanced hepatocellular carcinoma (HCC). METHODS: We retrospectively analyzed 78 patients with intermediate or advanced HCC who were treated at our centers between January 2018 and December 2021. 26 of them received sorafenib and camrelizumab plus TACE (the TACE + Sor + C group), while 52 received TACE and sorafenib (the TACE + Sor group). Overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were evaluated. Univariate and multivariate analyses were used to determine the factors affecting survival. RESULTS: The mOS (22 vs. 10 months, P < 0.001) and mPFS (11 vs. 6 months, P = 0.008) of the TACE + Sor + C group were significantly higher than those of the TACE + Sor group. Multivariate analysis showed that compared with TACE + Sor + C, TACE + Sor increased the risk of all-cause mortality and tumor progression. For grade I and II adverse events (AEs), the incidence of skin capillary hyperplasia and hypothyroidism in the TACE + Sor + C group was significantly higher than that in the TACE + Sor group. For serious AEs (grade III or IV), there was no significant difference in any adverse reaction between the two groups (P > 0.05). CONCLUSION: Patients with intermediate or advanced HCC appeared to benefit more in terms of survival from TACE + Sor + C than from TACE + Sor, and the AEs were tolerable. ADVANCES IN KNOWLEDGE: 1.Subgroup analysis demonstrated TACE+ Sorafenib+ Camrelizumab could benefit HCC patients regardless of whether they had PVTT, BCLC B or C, or CHILD A or B；2.We reported the immunotherapy related adverse events (irAEs) occurred with a significant higher incidence in triple treatment, but all the adverse events are tolerable.

Analysis of care-seeking and diagnosis delay among pulmonary tuberculosis patients in Beijing, China.

Background: Tuberculosis (TB) remains a significant public health challenge in China. Early detection and diagnosis of TB cases are crucial to interrupt disease transmission and prevent its progression. This study aims to describe the delay in seeking care and diagnosis among patients with pulmonary tuberculosis (PTB) and identify the influencing factors in two counties in Beijing. Methods: A retrospective analysis was carried out to investigate care-seeking and diagnosis delay in two counties in Beijing. Basic information of PTB patients from January 1 to December 31, 2021, was extracted from the Tuberculosis Information Management System of China (TBIMS), and all enrolled patients were interviewed via telephone using a standard questionnaire. Statistical description was performed using the median and interquartile range (IQR). Chi-square test and multivariate logistic regression model were used to analyze the influencing factors. Results: 537 patients were enrolled. The median duration of care-seeking and diagnosis delay was 11 (IQR: 5-26) days and 8 (IQR: 0-18) days, with 41.71 and 35.20% of patients experiencing delays (>14 days). The study found that being asymptomatic (OR = 2.791, 95%CI: 1.710-4.555) before seeking medical care and not attending work during treatment (OR = 2.990, 95%CI: 1.419-6.298) were identified as risk factors for care-seeking delay. Patients who were tracked (OR = 2.632, 95%CI: 1.062-6.521) and diagnosed at tuberculosis control and prevention institutions (OR = 1.843, 95%CI: 1.061-3.202) had higher odds of diagnostic delays. 44.69% of patients presented a total delay (>28 days), with a median duration of 25 (IQR: 13-39) days. A multivariate logistic regression analysis showed that healthy examination (OR = 0.136, 95%CI: 0.043-0.425) was a protective factor for total delay. Conclusion: Public interventions are necessary to improve the efficiency of PTB patients detection and treatment in Beijing. Medical services should focus on the target population and improve access to medical care to further reduce delays for PTB patients.

Effect of Welding Gap of Thin Plate Butt Welds on Inherent Strain and Welding Deformation of a Large Complex Box Structure.

In this study, an effective numerical model was developed for the calculation of the deformation of laser-welded 3 mm 304L stainless steel plates with different gaps (0.2 mm, 0.5 mm, and 1.0 mm). The welding deformation would become larger when the welding gaps increased, and the largest deformation values along the Z direction, of 4 mm, were produced when the gap value was 1.0 mm. A larger plastic strain region was generated in the location near the weld seam, since higher plastic deformation had occurred. In addition, the tensile stress model was also applied at the plastic strain zone and demonstrated that a larger welding gap led to a wider residual stress area. Based on the above results, inherent deformations for butt and corner joints were calculated according to inherent strain theory, and the welding formation for the complex structure was calculated with different gaps. The numerical results demonstrated that a larger deformation was also produced with a larger welding gap and that it could reach the highest value of 10.1 mm. This proves that a smaller welding gap should be adopted during the laser welding of complex structures to avoid excessive welding deformation.

Gram-scale synthesis of small-sized PtM intermetallics as high-performance catalysts for the hydrogen evolution reaction.

Pt-based intermetallics exhibit excellent activity in electrocatalysis. However, their controlled syntheses remain difficult. Herein, carbon-supported PtM (M = Fe, Co, Ni, Zn and Mn) intermetallics with small size (3 nm) were prepared at the gramscale and applied as a highly effective electrocatalyst for the hydrogen evolution reaction.

An Outbreak of Serogroup Y Meningococcal Meningitis in a Private Secondary Vocational School - Guangzhou City, Guangdong Province, China, 2023.

What is already known about this topic?: The inclusion of meningococcal vaccines in the National Immunization Program (NIP) over several years has significantly reduced the incidence of meningococcal meningitis in China to historic lows. Worldwide, there has been a diversification of meningococcal serogroups, leading to a shift in dominant serogroups in China from serogroup A to serogroups C and B, accompanied by a rise in reports of serogroups Y and W. What is added by this report?: An outbreak of serogroup Y Neisseria meningitidis (Nm) in a secondary vocational school involved a single confirmed severe case and 24 individuals with laboratory-confirmed Nm carriage. Epidemiological investigation revealed that the outbreak was localized to the classroom of the confirmed case. Prolonged close contact within a confined space was identified as a significant risk factor for Nm transmission. The genotype sequence identified was type 1655 (ST-1655), which is categorized under clonal complex 23 (CC-23) and bears resemblance to 8 previously confirmed cases of serogroup Y meningococcal meningitis within Guangdong Province. This suggests that serogroup Y infections continue to sporadically emerge and have become prevalent strains. What are the implications for public health practice?: This outbreak underscores the critical need to enhance surveillance of meningococcal serogroups and population carrier, and advocate for vaccination with MenY-containing vaccines.

In Vivo Toxicology of Metabolizable Atomically Precise Au25 Clusters at Ultrahigh Doses.

Ultrasmall Au25(MPA)18 clusters show great potential in biocatalysts and bioimaging due to their well-defined, tunable structure and properties. Hence, in vivo pharmacokinetics and toxicity of Au nanoclusters (Au NCs) are very important for clinical translation, especially at high dosages. Herein, the in vivo hematological, tissue, and neurological effects following exposure to Au NCs (300 and 500 mg kg-1) were investigated, in which the concentration is 10 times higher than in therapeutic use. The biochemical and hematological parameters of the injected Au NCs were within normal limits, even at the ultrahigh level of 500 mg kg-1. Meanwhile, no histopathological changes were observed in the Au NC group, and immunofluorescence staining showed no obvious lesions in the major organs. Furthermore, real-time near-infrared-II (NIR-II) imaging showed that most of the Au25(MPA)18 and Au24Zn1(MPA)18 can be metabolized via the kidney. The results demonstrated that Au NCs exhibit good biosafety by evaluating the manifestation of toxic effects on major organs at ultrahigh doses, providing reliable data for their application in biomedicine.

Gentisic acid prevents colorectal cancer metastasis via blocking GPR81-mediated DEPDC5 degradation.

BACKGROUND: Metastasis driven by epithelial-mesenchymal transition (EMT) remains a significant contributor to the poor prognosis of colorectal cancer (CRC), and requires more effective interventions. GPR81 signaling has been linked to tumor metastasis, while lacks an efficient specific inhibitor. PURPOSE: Our study aimed to investigate the effect and mechanism of Gentisic acid on colorectal cancer (CRC) metastasis. STUDY DESIGN: A lung metastasis mouse model induced by tail vein injection and a subcutaneous graft tumor model were used. Gentisic acid (GA) was administered by an intraperitoneal injection. HCT116 was treated with lactate to establish an in vitro model. METHODS: MC38 cells with mCherry fluorescent protein were injected into tail vein to investigate lung metastasis ability in vivo. GA was administered by intraperitoneal injection for 3 weeks. The therapeutic effect was evaluated by survival rates, histochemical analysis, RT-qPCR and live imaging. The mechanism was explored using small interfering RNA (siRNA), Western blotting, RT-qPCR and immunofluorescence. RESULTS: GA had a therapeutic effect on CRC metastasis and improved survival rates and pathological changes in dose-dependent manner. GA emerged as an GPR81 inhibitor, effectively suppressed EMT and mTOR signaling in CRC induced by lactate both in vivo and in vitro. Mechanistically, GA halted lactate-induce degradation of DEPDC5 through impeding the activation of Chaperone-mediated autophagy (CMA). CONCLUSION: CMA-mediated DEPDC5 degradation is crucial for lactate/GPR81-induced CRC metastasis, and GA may be a promising candidate for metastasis by inhibiting GPR81 signaling.

Mated-Atom Nanozymes with Efficient Assisted NAD+ Replenishment for Skin Regeneration.

Excessive accumulation of reduced nicotinamide adenine dinucleotide (NADH) within biological organisms is closely associated with many diseases. It remains a challenge to efficiently convert superfluous and detrimental NADH to NAD+. NADH oxidase (NOX) is a crucial oxidoreductase that catalyzes the oxidation of NADH to NAD+. Herein, M1M2 (Mi=V/Mn/Fe/Co/Cu/Mo/Rh/Ru/Pd, i = 1 or 2) mated-atom nanozymes (MANs) are designed by mimicking natural enzymes with polymetallic active centers. Excitingly, RhCo MAN possesses excellent and sustainable NOX-like activity, with Km-NADH (16.11 µM) being lower than that of NOX-mimics reported so far. Thus, RhCo MAN can significantly promote the regeneration of NAD+ and regulate macrophage polarization toward the M2 phenotype through down-regulation of TLR4 expression, which may help to recover skin regeneration. However, RhRu MAN with peroxidase-like activity and RhMn MAN with superoxide dismutase-like activity exhibit little modulating effects on eczema. This work provides a new strategy to inhibit skin inflammation and promote skin regeneration.

Exploration and Application of a Muscle Fatigue Assessment Model Based on NMF for Multi-Muscle Synergistic Movements.

Muscle fatigue significantly impacts coordination, stability, and speed in daily activities. Accurate assessment of muscle fatigue is vital for effective exercise programs, injury prevention, and sports performance enhancement. Current methods mostly focus on individual muscles and strength evaluation, overlooking overall fatigue in multi-muscle movements. This study introduces a comprehensive muscle fatigue model using non-negative matrix factorization (NMF) weighting. NMF is employed to analyze the duration multi-muscle weight coefficient matrix (DMWCM) during synergistic movements, and four electromyographic (EMG) signal features in time, frequency, and complexity domains are selected. Particle Swarm Optimization (PSO) optimizes feature weights. The DMWCM and weighted features combine to calculate the Comprehensive Muscle Fatigue Index (CMFI) for multi-muscle synergistic movements. Experimental results show that CMFI correlates with perceived exertion (RPE) and Speed Dynamic Score (SDS), confirming its accuracy and real-time tracking in assessing multi-muscle synergistic movements. This model offers a more comprehensive approach to muscle fatigue assessment, with potential benefits for exercise training, injury prevention, and sports medicine.

Transcatheter Arterial Embolization with Bleomycin-Lipiodol of Hepatic Hemangiomas: Safety, Efficacy and Predictors of Response.

PURPOSE: To evaluate the safety, efficacy and predictors of response of transcatheter arterial embolization (TAE) to treat hepatic hemangiomas (HHs). MATERIALS AND METHODS: A retrospective analysis was conducted of consecutive HH patients who received TAE with bleomycin-Lipiodol emulsion and gelatin sponge particles at three institutions from January 2014 to January 2021. TAE effectiveness was defined as more than 50% reduction of tumor volume. The effectiveness, safety, and CT changes of hemangiomas after TAE were assessed. Factors affecting TAE efficacy on tumor size were analyzed with logistic regression analysis. RESULTS: A total of 102 patients with 109 HHs were included. After treatment, both the tumor diameter and volume were significantly reduced from 8.5 ± 3.9 to 5.9 ± 3.8 cm (P < 0.001) and 412.6 ± 742.3 cm3 to 102.0 ± 232.7 cm3 (P < 0.001), respectively. TAE effectiveness was achieved in 80.7% (88/109) of hemangiomas, which was characterized by progressive reduction in tumor volume over time with Lipiodol retention. Atypical enhancement pattern (tiny enhancing dots in the hepatic arterial and portal venous phase) (p = 0.001) and central arterioportal shunt (APS) (p = 0.002) associated with the tumor were independent predictors of TAE ineffectiveness. Postembolization syndrome and transient increase in liver enzymes were common without severe complications and death. CONCLUSION: TAE was safe and effective in reducing HH size. Lesion enhancement pattern and APS type were associated with TAE efficacy on tumor shrinkage. LEVEL OF EVIDENCE: Level 3, non-controlled retrospective cohort study.

Correction: RNAi-Mediated Silencing of Atp6i and Atp6i Haploinsufficiency Prevents Both Bone Loss and Inflammation in a Mouse Model of Periodontal Disease.

[This corrects the article DOI: 10.1371/journal.pone.0058599.].

Vanillic acid restores homeostasis of intestinal epithelium in colitis through inhibiting CA9/STIM1-mediated ferroptosis.

The damage of integrated epithelial epithelium is a key pathogenic factor and closely associated with the recurrence of ulcerative colitis (UC). Here, we reported that vanillic acid (VA) exerted potent therapeutic effects on DSS-induced colitis by restoring intestinal epithelium homeostasis via the inhibition of ferroptosis. By the CETSA assay and DARTS assay, we identified carbonic anhydrase IX (CAIX, CA9) as the direct target of VA. The binding of VA to CA9 causes insulin-induced gene-2 (INSIG2) to interact with stromal interaction molecule 1 (STIM1), rather than SREBP cleavage-activating protein (SCAP), leading to the translocation of SCAP-SREBP1 from the endoplasmic reticulum (ER) to the Golgi apparatus for cleavage into mature SREBP1. The activation of SREBP1 induced by VA then significantly facilitated the transcription of stearoyl-CoA desaturase 1 (SCD1) to exert an inhibitory effect on ferroptosis. By inhibiting the excessive death of intestinal epithelial cells caused by ferroptosis, VA effectively preserved the integrity of intestinal barrier and prevented the progression of unresolved inflammation. In conclusion, our study demonstrated that VA could alleviate colitis by restoring intestinal epithelium homeostasis through CA9/STIM1-mediated inhibition of ferroptosis, providing a promising therapeutic candidate for UC.

Nanomaterials in 4D Printing: Expanding the Frontiers of Advanced Manufacturing.

As an innovative technology, four-dimentional (4D) printing is built upon the principles of three-dimentional (3D) printing with an additional dimension: time. While traditional 3D printing creates static objects, 4D printing generates "responsive 3D printed structures", enabling them to transform or self-assemble in response to external stimuli. Due to the dynamic nature, 4D printing has demonstrated tremendous potential in a range of industries, encompassing aerospace, healthcare, and intelligent devices. Nanotechnology has gained considerable attention owing to the exceptional properties and functions of nanomaterials. Incorporating nanomaterials into an intelligent matrix enhances the physiochemical properties of 4D printed constructs, introducing novel functions. This review provides a comprehensive overview of current applications of nanomaterials in 4D printing, exploring their synergistic potential to create dynamic and responsive structures. Nanomaterials play diverse roles as rheology modifiers, mechanical enhancers, function introducers, and more. The overarching goal of this review is to inspire researchers to delve into the vast potential of nanomaterial-enabled 4D printing, propelling advancements in this rapidly evolving field.

Computed tomography angiography-confirmed aortic in-stents floating thrombus after endovascular stenting: a retrospective study.

Background: Aortic in-stents floating thrombus (ASFT) is a rare complication. The evolution of ASFT on computed tomography angiography (CTA) imaging and the treatment options remain under investigations. The aim of this study was to analyze the imaging manifestations of ASFT on CTA, and to explore safe and effective treatment options. Methods: A retrospective, longitudinal study design was used. Clinical and imaging data were collected from patients with ASFT between January 2015 to December 2022 at the Union Hospital, Tongji Medical College, Huazhong University of Science and Technology. The imaging features of ASFT, including location, morphology, size, concomitant and dynamic changes during follow-up, were analyzed and classified into two types based on imaging manifestation. Type 1 showed a striated, irregular, or sheet-like appearance. Type 2 was a free-floating middle section in the cavity with attachment point to the thickened inner wall. The treatment protocol was also investigated. The Mann-Whitney U test was utilized for variable comparison. Results: A total of 1,626 cases were screened, out of which 10 cases were enrolled, resulting in an incidence rate of ASFT of 0.62% (10/1,626). The pre-surgery levels of fibrinogen (FIB), prothrombin time (PT), and D-dimer showed a higher trend, while only the D-dimer level increased significantly during the postoperative period (P<0.001). During the follow-up, CTA examination detected 21 ASFTs, including 18 ASFTs of type 1 and three ASFTs as type 2. One patient experienced spleen infarction when ASFT developed. During the follow-up period, thrombus disappeared in six patients, while the lesions remained stable in four patients. Renal infarction occurred in one case. No new-onset ASFTs or patient deaths were reported. Conclusions: ASFT is an extremely rare disease. The concomitant disorders and postoperative hemodynamic changes could be the cause. CTA examination presented as a safe and preferred imaging modality for evaluating the evolution and prognosis of ASFT. Conservative treatment may be a useful and effective option.

Twist-Angle Tuning of Electronic Structure in Two-Dimensional Dirac Nodal Line Semimetal Au2Ge on Au(111).

Topological semimetals have emerged as quantum materials including Dirac, Weyl, and nodal line semimetals, and so on. Dirac nodal line (DNL) semimetals possess topologically nontrivial bands crossing along a line or a loop and are considered precursor states for other types of semimetals. Here, we combine scanning tunneling microscopy/spectroscopy (STM/S) measurements and density functional theory (DFT) calculations to investigate a twist angle tuning of electronic structure in two-dimensional DNL semimetal Au2Ge. Theoretical calculations show that two bands of Au2Ge touch each other in Γ-M and Γ-K paths, forming a DNL. A significant transition of electronic structure occurs by tuning the twist angle from 30° to 24° between monolayer Au2Ge and Au(111), as confirmed by STS measurements and DFT calculations. The disappearing of DNL state is a direct consequence of symmetry breaking.

Prediction of Ki-67 expression in bladder cancer based on CT radiomics nomogram.

Objectives: This study aimed to create and validate a radiomics nomogram for non-invasive preoperative Ki-67 expression level prediction in patients with bladder cancer (BCa) using contrast-enhanced CT radiomics features. Methods: A retrospective analysis of 135 patients was conducted, 79 of whom had high levels of Ki-67 expression and 56 of whom had low levels. For the dimensionality reduction analysis, the best features were chosen using the least absolute shrinkage selection operator and one-way analysis of variance. Then, a radiomics nomogram was created using multiple logistic regression analysis based on radiomics features and clinical independent risk factors. The performance of the model was assessed using the Akaike information criterion (AIC) value, the area under the curve (AUC) value, accuracy, sensitivity, and specificity. The clinical usefulness of the model was assessed using decision curve analysis (DCA). Results: Finally, to establish a radiomics nomogram, the best 5 features were chosen and integrated with the independent clinical risk factors (T stage) and Rad-score. This radiomics nomogram demonstrated significant correction and discriminating performance in both the training and validation sets, with an AUC of 0.836 and 0.887, respectively. This radiomics nomogram had the lowest AIC value (AIC = 103.16), which was considered to be the best model. When compared to clinical factor model and radiomics signature, DCA demonstrated the more value of the radiomics nomogram. Conclusion: Enhanced CT-based radiomics nomogram can better predict Ki-67 expression in BCa patients and can be used for prognosis assessment and clinical decision making.

Effect of In Situ NbC-Cr7C3@graphene/Fe Nanocomposite Inoculant Modification and Refinement on the Microstructure and Properties of W18Cr4V High-Speed Steel.

A novel graphene-coated nanocrystalline ceramic particle, iron-based composite inoculant was developed in this study to optimize the as-cast microstructure and mechanical properties of W18Cr4V high-speed steel (HSS). The effects of the composite inoculant on the microstructure, crystal structure, and mechanical properties of HSS were analyzed using transmission electron microscopy, scanning electron microscopy, energy dispersive spectroscopy, and X-ray diffraction. The (002-) and (020) crystal planes of the Fe3C and Cr7C3 phases, respectively, were collinear at two points in the reciprocal space, indicating a coherent relationship between the Fe3C and Cr7C3 phases in the tempered modified HSS. This contributed to an improved non-uniform nucleation rate and refining of the HSS grains. The mechanical properties of the modified steel exhibited a general improvement. Specifically, the modification treatment enhanced the hardness of HSS from HRC 63.2 to 66.4 and the impact toughness by 48.3%.

ANGPTL3 is a novel HDL component that regulates HDL function.

BACKGROUND: Angiopoietin-like protein 3 (ANGPTL3) is secreted by hepatocytes and inhibits lipoprotein lipase and endothelial lipase activity. Previous studies reported the correlation between plasma ANGPTL3 levels and high-density lipoprotein (HDL). Recently ANGPTL3 was found to preferentially bind to HDL in healthy human circulation. Here, we examined whether ANGPTL3, as a component of HDL, modulates HDL function and affects HDL other components in human and mice with non-diabetes or type 2 diabetes mellitus. METHODS: HDL was isolated from the plasma of female non-diabetic subjects and type-2 diabetic mellitus (T2DM) patients. Immunoprecipitation, western blot, and ELISA assays were used to examine ANGPTL3 levels in HDL. Db/m and db/db mice, AAV virus mediated ANGPTL3 overexpression and knockdown models and ANGPTL3 knockout mice were used. The cholesterol efflux capacity induced by HDL was analyzed in macrophages preloaded with fluorescent cholesterol. The anti-inflammation capacity of HDL was assessed using flow cytometry to measure VCAM-1 and ICAM-1 expression levels in TNF-α-stimulated endothelial cells pretreated with HDL. RESULTS: ANGPTL3 was found to bind to HDL and be a component of HDL in both non-diabetic subjects and T2DM patients. Flag-ANGPTL3 was found in the HDL of transgenic mice overexpressing Flag-ANGPTL3. ANGPLT3 of HDL was positively associated with cholesterol efflux in female non-diabetic controls (r = 0.4102, p = 0.0117) but not in female T2DM patients (r = - 0.1725, p = 0.3224). Lower ANGPTL3 levels of HDL were found in diabetic (db/db) mice compared to control (db/m) mice and were associated with reduced cholesterol efflux and inhibition of VCAM-1 and ICAM-1 expression in endothelial cells (p < 0.05 for all). Following AAV-mediated ANGPTL3 cDNA transfer in db/db mice, ANGPTL3 levels were found to be increased in HDL, and corresponded to increased cholesterol efflux and decreased ICAM-1 expression. In contrast, knockdown of ANGPTL3 levels in HDL by AAV-mediated shRNA transfer led to a reduction in HDL function (p < 0.05 for both). Plasma total cholesterol, total triglycerides, HDL-c, protein components of HDL and the cholesterol efflux function of HDL were lower in ANGPTL3-/- mice than ANGPTL3+/+ mice, suggesting that ANGPTL3 in HDL may regulate HDL function by disrupting the balance of protein components in HDL. CONCLUSION: ANGPTL3 was identified as a component of HDL in humans and mice. ANGPTL3 of HDL regulated cholesterol efflux and the anti-inflammatory functions of HDL in T2DM mice. Both the protein components of HDL and cholesterol efflux capacity of HDL were decreased in ANGPTL3-/- mice. Our findings suggest that ANGPTL3 in HDL may regulate HDL function by disrupting the balance of protein components in HDL. Our study contributes to a more comprehensive understanding of the role of ANGPTL3 in lipid metabolism.