CircPIAS1 promotes hepatocellular carcinoma progression by inhibiting ferroptosis via the miR-455-3p/NUPR1/FTH1 axis.

BACKGROUND: The role of circRNAs in hepatocellular carcinoma (HCC) progression remains unclear. CircPIAS1 (circBase ID: hsa_circ_0007088) was identified as overexpressed in HCC cases through bioinformatics analysis. This study aimed to investigate the oncogenic properties and mechanisms of circPIAS1 in HCC development. METHODS: Functional analyses were conducted to assess circPIAS1's impact on HCC cell proliferation, migration, and ferroptosis. Xenograft mouse models were employed to evaluate circPIAS1's effects on tumor growth and pulmonary metastasis in vivo. Bioinformatics analysis, RNA immunoprecipitation, and luciferase reporter assays were utilized to elucidate the molecular pathways influenced by circPIAS1. Additional techniques, including RNA pulldown, fluorescence in situ hybridization (FISH), chromatin immunoprecipitation (ChIP), qPCR, and western blotting, were used to further explore the underlying mechanisms. RESULTS: CircPIAS1 expression was elevated in HCC tissues and cells. Silencing circPIAS1 suppressed HCC cell proliferation and migration both in vitro and in vivo. Mechanically, circPIAS1 overexpression inhibited ferroptosis by competitively binding to miR-455-3p, leading to upregulation of Nuclear Protein 1 (NUPR1). Furthermore, NUPR1 promoted FTH1 transcription, enhancing iron storage in HCC cells and conferring resistance to ferroptosis. Treatment with ZZW-115, an NUPR1 inhibitor, reversed the tumor-promoting effects of circPIAS1 and sensitized HCC cells to lenvatinib. CONCLUSION: This study highlights the critical role of circPIAS1 in HCC progression through modulation of ferroptosis. Targeting the circPIAS1/miR-455-3p/NUPR1/FTH1 regulatory axis may represent a promising therapeutic strategy for HCC.

Exosome-transported circ_0061407 and circ_0008103 play a tumour-repressive role and show diagnostic value in non-small-cell lung cancer.

BACKGROUND: Circular RNAs (circRNAs), one of the major contents of exosomes, have been shown to participate in the occurrence and progression of cancers. The role and the diagnostic potential of exosome-transported circRNAs in non-small-cell lung cancer (NSCLC) remain largely unknown. METHODS: The NSCLC-associated exosomal circ_0061407 and circ_0008103 were screened by circRNA microarray. The role of circ_0061407 and circ_0008103 in NSCLC was examined in vitro and in vivo. The encapsulation of the two circRNAs into exosomes and the transport to recipient cells were observed by confocal microscopy. The effects of exosome-transported circ_0061407 and circ_0008103 on recipient cells were investigated using a co-culture device. Bioinformatics analyses were performed to predict the mechanisms by which circ_0061407 and circ_0008103 affected NSCLC. The quantitative polymerase chain reaction was used to quantify the exosome-containing circ_0061407 and circ_0008103 in the serum samples of healthy, pneumonia, benign lung tumours, and NSCLC. The diagnostic efficacy was evaluated using receiver operating characteristic curves. RESULTS: The levels of circ_0061407 and circ_0008103 within exosomes were down-regulated in the serum of patients with NSCLC. The up-regulation of circ_0061407 and circ_0008103 inhibited the proliferation, migration/invasion, cloning formation of NSCLC cells in vitro and inhibited lung tumour growth in vivo. Circ_0061407 and circ_0008103 were observed to be packaged in exosomes and transported to recipient cells, where they inhibited the proliferation, migration/invasion, and cloning formation abilities of the recipient cells. Moreover, circ_0061407 and circ_0008103 might be involved in the progression of NSCLC by interacting with microRNAs and proteins. Additionally, lower serum exosomal circ_0061407 and circ_0008103 levels were associated with advanced pathological staging and distant metastasis. CONCLUSIONS: This study identified two novel exosome-transported circRNAs (circ_0061407 and circ_0008103) associated with NSCLC. These findings may provide additional insights into the development of NSCLC and potential diagnostic biomarkers for NSCLC.

Association between the ROX index and mortality in patients with acute hypoxemic respiratory failure: a retrospective cohort study.

BACKGROUND: Although ROX index is frequently used to assess the efficacy of high-flow nasal cannula treatment in acute hypoxemic respiratory failure (AHRF) patients, the relationship between the ROX index and the mortality remains unclear. Therefore, a retrospective cohort study was conducted to evaluate the ability of the ROX index to predict mortality risk in patients with AHRF. METHOD: Patients diagnosed with AHRF were extracted from the MIMIC-IV database and divided into four groups based on the ROX index quartiles. The primary outcome was 28-day mortality, while in-hospital mortality and follow-up mortality were secondary outcomes. To investigate the association between ROX index and mortality in AHRF patients, restricted cubic spline curve and COX proportional risk regression were utilized. RESULT: A non-linear association (L-shaped) has been observed between the ROX index and mortality rate. When the ROX index is below 8.28, there is a notable decline in the 28-day mortality risk of patients as the ROX index increases (HR per SD, 0.858 [95%CI 0.794-0.928] P < 0.001). When the ROX index is above 8.28, no significant association was found between the ROX index and 28-day mortality. In contrast to the Q1 group, the mortality rates in the Q2, Q3, and Q4 groups had a substantial reduction (Q1 vs. Q2: HR, 0.749 [0.590-0.950] P = 0.017; Q3: HR, 0.711 [0.558-0.906] P = 0.006; Q4: HR, 0.641 [0.495-0.830] P < 0.001). CONCLUSION: The ROX index serves as a valuable predictor of mortality risk in adult patients with AHRF, and that a lower ROX index is substantially associated with an increase in mortality.

Design, synthesis, and bioevaluation of SOS1 PROTACs derived from pyrido[2,3-d]pyrimidin-7-one-based SOS1 inhibitor.

Oncogenic KRAS mutations drive an approximately 25 % of all human cancers. Son of Sevenless 1 (SOS1), a critical guanine nucleotide exchange factor, catalyzes the activation of KRAS. Targeting SOS1 degradation has engaged as a promising therapeutic strategy for KRAS-mutant cancers. Herein, we designed and synthesized a series of novel CRBN-recruiting SOS1 PROTACs using the pyrido[2,3-d]pyrimidin-7-one-based SOS1 inhibitor as the warhead. One representative compound 11o effectively induced the degradation of SOS1 in three different KRAS-mutant cancer cell lines with DC50 values ranging from 1.85 to 7.53 nM. Mechanism studies demonstrated that 11o-induced SOS1 degradation was dependent on CRBN and proteasome. Moreover, 11o inhibited the phosphorylation of ERK and displayed potent anti-proliferative activities against SW620, A549 and DLD-1 cells. Further optimization of 11o may provide us promising SOS1 degraders with favorable drug-like properties for developing new chemotherapies targeting KRAS-driven cancers.

Synthesis and Characterization of 6-Ti-Substituted Polyoxomolybdate with High Catalytic Activity for Sulfide Oxidation.

A 6-Ti-substituted polyoxometalate, (NH4)5Cs7Na3H2[Cs@(Ti2GeMo10O39)3]·34H2O (1), was synthesized by reacting (NH4)6Mo7O24·4H2O, GeO2, and TiOSO4 through the conventional aqueous method. Polyanion 1a is composed of three {Ti2GeMo10} segments linked by Ti-O-Ti linkages and shows a trefoil-shaped structure. Furthermore, one Cs+ cation is encapsulated in the cavity of 1a. Notably, it possesses the highest number of Ti centers among the reported polyoxomolybdates. In addition, serving as a high-efficiency heterogeneous catalyst, 1 enables the conversion of methyl phenyl sulfide within 20 min, yielding 96.4% of the corresponding sulfoxide with good recyclability.

The role and regulation of SIRT1 in pulmonary fibrosis.

Pulmonary fibrosis (PF) is a progressive and fatal lung disease with high incidence and a lack of effective treatment, which is a severe public health problem. PF has caused a huge socio-economic burden, and its pathogenesis has become a research hotspot. SIRT1 is a nicotinamide adenosine dinucleotide (NAD)-dependent sirtuin essential in tumours, Epithelial mesenchymal transition (EMT), and anti-aging. Numerous studies have demonstrated after extensive research that it is crucial in preventing the progression of pulmonary fibrosis. This article reviews the biological roles and mechanisms of SIRT1 in regulating the progression of pulmonary fibrosis in terms of EMT, oxidative stress, inflammation, aging, autophagy, and discusses the potential of SIRT1 as a therapeutic target for pulmonary fibrosis, and provides a new perspective on therapeutic drugs and prognosis prospects.

Precision Cardio-oncology: Update on Omics-Based Diagnostic Methods.

OPINION STATEMENT: Cardio-oncology is an emerging interdisciplinary field dedicated to the early detection and treatment of adverse cardiovascular events associated with anticancer treatment, and current clinical management of anticancer-treatment-related cardiovascular toxicity (CTR-CVT) remains limited by a lack of detailed phenotypic data. However, the promise of diagnosing CTR-CVT using deep phenotyping has emerged with the development of precision medicine, particularly the use of omics-based methodologies to discover sensitive biomarkers of the disease. In the future, combining information produced by a variety of omics methodologies could expand the clinical practice of cardio-oncology. In this review, we demonstrate how omics approaches can improve our comprehension of CTR-CVT deep phenotyping, discuss the positive and negative aspects of available omics approaches for CTR-CVT diagnosis, and outline how to integrate multiple sets of omics data into individualized monitoring and treatment. This will offer a reliable technical route for lowering cardiovascular morbidity and mortality in cancer patients and survivors.

HSP gene superfamily in Aspongopus chinensis Dallas: unravelling identification, characterisation and expression patterns during diapause and non-diapause stages.

Aspongopus chinensis Dallas 1851, an insect of important economic value, faces challenges in artificial breeding due to mandatory diapause and limited access to wild resources. Heat shock proteins (Hsps) are thought to influence diapause in insects, but little is known about their role in A. chinensis during diapause. This study used genomic methods to identify 25 Hsp genes in A. chinensis, including two Hsp90, 14 Hsp70, four Hsp60 and five small Hsp genes, were located on seven chromosomes, respectively. The gene structures among the same families are relatively conserved. Meanwhile, the motif compositions and secondary structures of A. chinensis Hsps (AcHsps) were predicted. RNA-seq data and fluorescence quantitative PCR analysis showed that there were differences in the expression patterns of AcHsps in diapause and non-diapause stages, and AcHsp70-5 was significantly differentially expressed in both analysis, which was enriched in the pathway of response to hormone. All the results showed that Hsps play an important role in the diapause mechanism of A. chinensis. Our observations highlight the molecular evolution of the Hsp gene and their effect on diapause in A. chinensis.

Reducing the mass and decreasing the bioavailability of heavy mental from organic wastes treated by black soldier fly larvae.

Black soldier fly larvae (BSFL), Hermetia illucens L., are widely used to reduce the mass of various wastes. However, the potential metal tolerance mechanisms during periods of waste bioconversion by BSFL remain largely unknown. To further reveal the mechanisms, BSFL were used to treat the agricultural organic wastes, including pig manure (PM), cow manure (COM), spent mushroom substrate (SMS), and wet distiller grains (WDG). After these individual and combined waste(s) were treated by BSFL, we investigated the waste reduction rates and evaluated the responses of BSFL gut microbes to heavy metals of agricultural organic wastes. Additionally, the colloidal particles of residual wastes were characterized by combing energy dispersive X-ray (EDX) spectroscopy, Size potential, Zeta potential, and excitation-emission matrix (EEM) spectroscopy. Results indicated that the waste reduction rates were up to 74% in COM+WDG and 69% in WDG, most of heavy metals (e.g., Zn and Co) from organic wastes were not accumulated in the bodies of mature larvae after treatment. Further, results obtained from the prediction of gene function on the basis of 16 S rRNA data revealed that the presence of multi-resistance genes in the gut of BSFL can help the larvae resist Zn and/or Co stress. In addition, the drug sensitivity test implied that BSFL5_L and BSFL6_L from BSFL gut bacterial strains have multi-resistance to Co and Zn. Additionally, EDX results revealed that the colloidal particles in five waste residues after BSFL treatment are mainly consisted of Fe, Ca and Si, which can capture heavy metals (e.g., Cu, Mn). Results from EEM spectroscopy and PARAFAC showed that tryptophan-like and humic-like accumulatively account for 56%- 68% of all components. Importantly, these two components could strongly bind the metal elements and form colloidal particles with high stability, and therefore reduce the heavy metal pollution of agricultural organic wastes. Our findings offered an environment-friendly method to treat agricultural organic wastes, which would be far-reaching influence to our environment.

Chemical Constituents with Anti-Proliferative Activity on Pulmonary Arterial Smooth Muscle Cells from the Roots of Anthriscus sylvestris (L.) Hoffm.

A chemical investigation of Anthriscus sylvestris roots led to the isolation and characterization of two new nitrogen-containing phenylpropanoids (1-2) and two new phenol glycosides (8-9), along with fifteen known analogues. Structure elucidation was based on HRESIMS, 1D and 2D NMR spectroscopy, and electronic circular dichroism (ECD). In addition, compounds 3, 6, 9-10, 12, and 17 exhibited inhibitory effects against the abnormal proliferation of pulmonary arterial smooth muscle cells with IC50 values ranging from 10.7 ± 0.6 to 57.1 ± 1.1 µM.

Simplified and modified Limberg flap plus vacuum-assisted closure for treatment of sacrococcygeal pilonidal sinus disease.

BACKGROUND: Pilonidal sinus disease (PSD), a chronic inflammatory disease, affects the sacrococcygeal soft tissue, especially in young adults. The ideal treatment for PSD remains divergence. This study evaluated the application of a simplified modified Limberg flap combined with vacuum-assisted closure for treating PSD. METHODS: This prospective study was conducted from 1 June 2017 to 31 March 2022 in Changhai Hospital, Naval Military Medical University, Shanghai, China. The study included 88 male patients (91.7%) and 8 female patients (8.3%). The 96 patients ranged in age from 15 to 34 years (mean ± SD, 23 ± 4.4). Under general anaesthesia, all patients underwent simplified modified Limberg flap reconstruction with vacuum-assisted closure. The patient's weight, surgical time, extubation time, hospital stay, time to return to normal life or work, wound infection, wound dehiscence and recurrence rate were recorded. The visual analogue scale (VAS) score and the Vancouver scar score were used to score patients' pain and scars in the surgical area. RESULTS: The volume of resected diseased tissue was 13.5-120 (mean ± SD, 34.993 ± 24.406) cm2 . The average surgical time during the treatment period was 97.68 ± 18.72 min, and the average extubation time was (6.36 ± 1.55) days, the mean hospital stay was 19.4 days; no patients were lost to follow-up. None of the patients experienced post-operative recurrence, wound infection, seroma or hematoma. Six patients (6.3%) experienced wound dehiscence at the flap tip around the natal cleft. The mean time to the resumption of daily activities was 26.3 days. The average VAS pain score was (6.00 ± 1.53) points, and the average Vancouver scar score was (5.96 ± 1.51) points, 12 patients (12.5%) were dissatisfied with their aesthetic results, and the average beauty satisfaction score is (6.64 ± 1.28) points. CONCLUSIONS: Simplified modified Limberg flap reconstruction with vacuum-assisted closure surgery is an effective and innovative method for the treatment of PSD, with a low recurrence rate and rapid recovery.

Synthesis and Structure of High-Nuclearity Carboxylate-Modified Heteropolyoxovanadate Serving as a Heterogeneous Catalyst for Selective Oxidation of Alkylbenzenes.

A high-nuclearity carboxylic-modified heteropolyoxovanadate, Na2K10H15[P8VIV24(tart)15(H2O)15(OH)O51]·58H2O [1, tart = C4H2O6], has been successfully synthesized by a conventional aqueous method under mild conditions. The crystallographic study reveals that compound 1 crystallizes in the tetragonal I41/a space group and is composed by a trilayer saddle-like polyoxoanion {P8V24}. Two {V3(tart)(H2O)O11} as linking units bridge the top {P4VIV9(tart)7(H2O)4(OH)O23} and the bottom {P4VIV9(tart)6(H2O)9O22} layers via tartrate ligands and {PO4} tetrahedra, resulting in a 24-nuclearity POV skeleton structure. More interestingly, compound 1 serves as a heterogeneous catalyst for the selective oxidation of diphenylmethanes with 96.2% conversion and 93.6% selectivity under the optimized conditions.

Single-nucleus RNA-seq identifies divergent populations of FSHD2 myotube nuclei.

FSHD is characterized by the misexpression of DUX4 in skeletal muscle. Although DUX4 upregulation is thought to be the pathogenic cause of FSHD, DUX4 is lowly expressed in patient samples, and analysis of the consequences of DUX4 expression has largely relied on artificial overexpression. To better understand the native expression profile of DUX4 and its targets, we performed bulk RNA-seq on a 6-day differentiation time-course in primary FSHD2 patient myoblasts. We identify a set of 54 genes upregulated in FSHD2 cells, termed FSHD-induced genes. Using single-cell and single-nucleus RNA-seq on myoblasts and differentiated myotubes, respectively, we captured, for the first time, DUX4 expressed at the single-nucleus level in a native state. We identified two populations of FSHD myotube nuclei based on low or high enrichment of DUX4 and FSHD-induced genes ("FSHD-Lo" and "FSHD Hi", respectively). FSHD-Hi myotube nuclei coexpress multiple DUX4 target genes including DUXA, LEUTX and ZSCAN4, and also upregulate cell cycle-related genes with significant enrichment of E2F target genes and p53 signaling activation. We found more FSHD-Hi nuclei than DUX4-positive nuclei, and confirmed with in situ RNA/protein detection that DUX4 transcribed in only one or two nuclei is sufficient for DUX4 protein to activate target genes across multiple nuclei within the same myotube. DUXA (the DUX4 paralog) is more widely expressed than DUX4, and depletion of DUXA suppressed the expression of LEUTX and ZSCAN4 in late, but not early, differentiation. The results suggest that the DUXA can take over the role of DUX4 to maintain target gene expression. These results provide a possible explanation as to why it is easier to detect DUX4 target genes than DUX4 itself in patient cells and raise the possibility of a self-sustaining network of gene dysregulation triggered by the limited DUX4 expression.

Kaempferol induces mitochondrial dysfunction and mitophagy by activating the LKB1/AMPK/MFF pathway in breast precancerous lesions.

Kaempferol has been suggested to be an effective anticancer agent in several malignant tumors. However, its function and mechanisms in breast precancerous lesions remain largely elusive. Here, we showed that kaempferol induced excessive mitochondrial fission and mitochondrial damage with activated mitochondrial fission factor (MFF)-mediated dynamin-related protein (DRP) 1 mitochondrial translocation. As a result, the PTEN-induced putative kinase 1 (PINK1)/Parkin signaling pathway was activated, accompanied by excessive mitophagy and reduced mitochondrial mass in cells. We also revealed that kaempferol-induced lethal mitophagy contributed to inhibiting breast precancerous lesion growth in vitro and in vivo. Furthermore, we verified serine/threonine kinase 11 (STK11/LKB1)/AMP-activated protein kinase (AMPK) pathway deficiency in breast precancerous lesions. Moreover, LKB1/AMPK pathway reactivation by kaempferol was required for excessive mitochondrial fission and lethal mitophagy. Taken together, our findings shed new light on the molecular mechanisms related to breast cancer prevention by kaempferol and provide evidence for its potential clinical application.

Transcriptome analyses shed light on floral organ morphogenesis and bract color formation in Bougainvillea.

BACKGROUND: Bougainvillea is a popular ornamental plant with brilliant color and long flowering periods. It is widely distributed in the tropics and subtropics. The primary ornamental part of the plant is its colorful and unusual bracts, rich in the stable pigment betalain. The developmental mechanism of the bracts is not clear, and the pathway of betalain biosynthesis is well characterized in Bougainvillea. RESULTS: At the whole-genome level, we found 23,469 protein-coding genes by assembling the RNA-Seq and Iso-Seq data of floral and leaf tissues. Genome evolution analysis revealed that Bougainvillea is related to spinach; the two diverged approximately 52.7 million years ago (MYA). Transcriptome analysis of floral organs revealed that flower development of Bougainvillea was regulated by the ABCE flower development genes; A-class, B-class, and E-class genes exhibited high expression levels in bracts. Eight key genes of the betalain biosynthetic pathway were identified by homologous alignment, all of which were upregulated concurrently with bract development and betalain accumulation during the bract initiation stage of development. We found 47 genes specifically expressed in stamens, including seven highly expressed genes belonging to the pentose and glucuronate interconversion pathways. BgSEP2b, BgSWEET11, and BgRD22 are hub genes and interacted with many transcription factors and genes in the carpel co-expression network. CONCLUSIONS: We assembled protein-coding genes of Bougainvilea, identified the floral development genes, and constructed the gene co-expression network of petal, stamens, and carpel. Our results provide fundamental information about the mechanism of flower development and pigment accumulation in Bougainvillea, and will facilitate breeding of cultivars with high ornamental value.

A High-Nuclear Isopolymolybdate Cluster Assembled with an Anionic [{Mo24 O48 (OMe)32 }]8- and Two Charge-Neutral [{Mo24 O52 (OMe)28 }] Cages.

We synthesized a high-nuclear isopolymolybdate cluster (n-Bu4 N)6 H2 [{Mo24 O48 (OMe)32 }{Mo24 O52 (OMe)28 }2 ] ⋅ 25H2 O ⋅ 6CH3 CN (1) by using [Mo6 O19 ]2- as the base precursor. Crystallographic characterization shows the cluster is composed of an anionic [{Mo24 O48 (OMe)32 }]8- cage and two charge-neutral [{Mo24 O52 (OMe)28 }] cages. Supported by the electrospray ionization mass spectrometry study, the polyoxoanion structural unit [Mo24 O48 (CH3 O)27 ]3- demonstrates strong stability in acetonitrile solution. Moreover, 1 exhibits good proton conductivity of 1.79×10-3  S cm-1 at 358 K and 98 % relative humidity.

Ring-Opening Selenation of Cyclopropanol for the Selective Synthesis of ß-Hydroxy-Substituted Selenylated Ketones.

Ring opening of cycloalkanols has been employed as a commonly used strategy to prepare diverse distal functionalized ketones. However, most of these ketones obtained by this strategy belong to monofunctional ketones, while difunctional ketones with more potential application value have been rarely reported. Herein, we first reported a mild I2-promoted ring-opening selenation of cyclopropanol to synthesize various distal difunctional ketones. In the reaction, hydroxyl (-OH) derived from water and RSe+ from diselenide can be introduced into the α- and ß-positions, respectively, delivering ß-hydroxy selenylated ketones in good to excellent yields.

Copper-Containing Polyoxometalate-Based Metal-Organic Framework as a Catalyst for the Oxidation of Silanes: Effective Cooperative Catalysis by Metal Sites and POM Precursor.

The oxidation of silanes into silanols is a very necessary transformation, and yet the rational fabrication of efficient catalysts for this reaction remains a challenging task. Here, a 3D polyoxometalate-based metal-organic framework (POMOF), [CuΙ3(pz)3{PMo12O40}]·H2O (HENU-8, HENU = Henan University; pz = pyrazine) was consciously prepared and first employed in the oxidation of dimethylphenylsilane with tert-butyl hydroperoxide (TBHP) as an oxidant, achieving 89% yield at a production rate of 132 mmol·g-1·h-1. Control experiments indicated that polyoxometalates and Cu atoms together affected the ultimate outcome in this catalytic system, and the designed catalyst followed a free radical mechanism.

Rocket-Shaped Telluroniobate with Efficient Catalytic Activity in the Transesterification Reaction.

A novel telluroniobate, K8Na6H7{[Co(en)2(SO3)][Te4Nb24O79]}·42H2O (en = ethylenediamine), has been synthesized through a diffusion strategy. It consists of a heteropolyoxoniobate [B-ß-TeNb9O33]17- cluster and isopolyoxoniobate {Nb7O22} building blocks. In addition, its structure was fully characterized by a series of spectroscopic methods. Furthermore, it exhibits an efficient catalytic performance in the transesterification of ethylene carbonate and methanol to prepare dimethyl carbonate with good catalytic reusability. Also, it demonstrates interesting proton conduction properties, with conductivity achieved at 3.05 × 10-4 S cm-1 (60 °C, 75% relative humidity).

Interaction between the HIF-1α gene rs1957757 polymorphism and CpG island methylation in the promoter region is associated with the risk of anti-tuberculosis drug-induced liver injury in humans: A case-control study.

WHAT IS KNOWN AND OBJECTIVE: HIF-1α gene polymorphisms, including rs11549465, rs11549467, rs1957757 and rs10873142, cause liver cell damage or pulmonary disease. The aim of this study was to analyse the association between the polymorphisms of the loci of the HIF-1α gene and its CpG island methylation in the promoter region with the risk of anti-tuberculosis drug-induced liver injury (ADLI). METHODS: 286 patients with tuberculosis (TB) and ADLI (case group) and 286 patients with TB but without liver injury (control group) were matched one-to-one, among the 1728 TB patients recruited from July 2019 to July 2020. Genotyping of the four loci of the HIF-1α gene was confirmed using PCR-RFLP technology. Methylation of the HIF-1α gene was measured using the MSP method. The comparison of risk factors, HIF-1α genotype and methylation status between the case group and the control group was all achieved through univariate and multivariate conditional logistic regression. RESULTS AND DISCUSSION: Univariate analysis showed that the frequency of rs1957757 mutation genotype and CpG island methylation was significantly higher in the case group than in the control group (P<0.001, all). In contrast, there was no statistical difference in the frequency of mutated genotypes at the other three loci between the two groups (p = 0.21, p = 0.12 and p = 0.55, respectively). Further, multivariate analysis showed that CpG islands were methylated, the mutation genotype of the rs1957757 locus was independently associated with the high risk of ADLI, and the adjusted OR (95%CI) reached 1.92 (1.32-2.63) and 2.01 (1.32-2.83), respectively. Furthermore, taking the rs1957757 locus wild genotype and CpG islands without methylation as the reference group, the mutation genotype and CpG island methylation increased the risk of ADLI, and the probability of ADLI could reach 4.73 times that of the reference group. WHAT IS NEW AND CONCLUSION: This is the first demonstration of the association of HIF-1α gene polymorphism and CpG island methylation with ADLI risk stratification. The interaction between CpG islands methylated in the promoter region of the HIF-1α gene and its rs1957757 locus mutant genotype was associated with a higher risk of ADLI.