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Pancreatic cancer is one of the leading causes of cancer-associated mortality, with a poor treatment approach. Previous study has shown that inducing pyroptosis in pancreatic ductal adenocarcinoma (PDAC) slows the growth of PDACs, implying that pyroptosis inducers are potentially effective for PDAC therapy. Here, we found that Dronedarone hydrochloride (DH), an antiarrhythmic drug, induces pyroptosis in pancreatic cancer cells and inhibits PDAC development in mice. In PANC-1 cells, DH caused cell death in a dosage- and time-dependent manner, with only pyroptosis inhibitors and GSDMD silencing rescuing the cell death, indicating that DH triggered GSDMD-dependent pyroptosis. Further work revealed that DH increased mitochondrial stresses and caused mitochondrial DNA (mtDNA) leakage, activating the cytosolic STING-cGAS and pyroptosis pathways. Finally, we assessed the anti-cancer effects of DH in a pancreatic cancer mouse model and found that DH treatment suppressed pancreatic tumor development in vivo. Collectively, our investigation demonstrates that DH triggers pyroptosis in PDAC and proposes its potential effects on anti-PDAC growth.
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DNA Mitocondrial , Dronedarona , Neoplasias Pancreáticas , Piroptose , Piroptose/efeitos dos fármacos , Animais , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/genética , Humanos , Dronedarona/farmacologia , DNA Mitocondrial/metabolismo , DNA Mitocondrial/genética , Camundongos , Linhagem Celular Tumoral , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/genética , Camundongos NusRESUMO
Objective: To assess whether cumulative exposure of unhealthy lifestyles is associated with HTH in Chinese adults and to explore the combination of unhealthy lifestyles. Methods: This study combined a community-based cross-sectional study with a 1:1 matched case-control study using propensity scores among adults in six randomly selected districts from Hunan Province, China. We recruited 5,258 people, of whom 4,012 met the criteria. Lifestyles and personal characteristics were collected by a questionnaire. Lifestyle score was calculated using cigarette smoking, heavy alcohol consumption, inactive exercise, unhealthy diet and abnormal BMI. HTH was defined as having a diagnosis of essential hypertension with Hcy ≥ 15 umol/L. Logistic regression models and multivariate analyses were used to explore the associations. We calculated odds ratios (ORs) and attributable risk proportion (ARP) for the association of HTH with lifestyle score. The dose-response relationship was evaluated using restricted cubic splines method. Results: Of the 4,012 adults, 793 had HTH, with a population prevalence of 19.8%. In the propensity-score-matched case-control study, 1,228 (614 cases and 614 controls) were included, and those with at least four unhealthy lifestyle factors had a higher risk of HTH than those with 0 unhealthy lifestyle factor (adjusted OR = 2.60, 95%CI:1.42-4.78), with an ARP of the cumulative exposure of unhealthy lifestyle was 28.23% (95% CI: 6.34-37.86%). For three unhealthy lifestyles group, the combination of heavy alcohol consumption, unhealthy diet and BMI ≥24 Kg/m2 was most associated with HTH (OR = 7.49, 95%CI: 1.12-50.08). For four unhealthy lifestyles group, the combination of smoking, heavy alcohol consumption, unhealthy diet and BMI ≥24 Kg/m2 had the greatest correlation with HTH (OR = 3.75, 95%CI: 1.24-7.38). Notably, there was a monotonically increasing curve (J-shaped) relationship between unhealthy lifestyles and the risk of HTH (p = 0.014). Conclusion: Our findings suggest that there was a significant cumulative exposure effect of unhealthy lifestyles on the risk of HTH, with the largest effect combination being heavy alcohol consumption, unhealthy diet and BMI ≥24 Kg/m2. Targeted interventions that reducing heavy alcohol consumption, quitting smoking, promoting physical activity and a healthy diet, and keep a normal BMI could substantially reduce the burden of HTH.
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The rapid and accurate detection of programmed death-ligand 1 (PD-L1) expression is of great value in the diagnosis and treatment of tumors. ELISA-based traditional method is the gold standard for protein detection, but there are still some shortcomings, especially the antigen-antibody dependence, greatly increased the detection time and cost. This work constructed a label-free fluorescent probe for rapid and sensitive detection of PD-L1 using a truncated aptamer as recognition molecules and double-stranded DNA specific dyes (SYBR Green I) as signal units. After a series of optimization conditions, this probe has good detection capability for PD-L1 in buffer solution with the detection limit as low as 0.68 ng/mL. Due to the specific recognition ability of aptamer and target, this method also has good selectivity for PD-L1 detection. The recovery of PD-L1 in human serum samples ranges from 86.20 to 96.36%. Compared with other methods, this strategy does not need to be marked, and does not need other complex design and purification process, but simple operation process and strong anti-interference ability. The whole detection process can be completed within 20 min and has good application prospect. This work will provide reference for drug dosage and prognosis evaluation of specific tumor therapy.
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Background: Hemorrhoids are common conditions at or around the anus, to which numerous people suffer worldwide. Previous research has suggested that microbes may play a role in the development of hemorrhoids, and the origins of these microbes have been preliminarily investigated. However, no detailed research on the microbes related to hemorrhoid patients has been conducted. This work aims to provide an initial investigation into the microbes related to hemorrhoid patients with high quality whole genome sequencing. Methods: Forty-nine bacterial strains were isolated from seven hemorrhoid patients. Third-generation nanopore sequencing was performed to obtain high quality whole genome sequences. The presence of plasmids, particularly new plasmids, along with antibiotic resistance genes, was investigated for these strains. Phylogenetic analysis and genome comparisons were performed. Results: Out of the 31 plasmids found in the strains, 15 new plasmids that have not been observed previously were discovered. Further structural analysis revealed new multidrug-resistant conjugative plasmids, virulent plasmids, and small, high-copy mobile plasmids that may play significant functional roles. These plasmids were found to harbor numerous integrases, transposases, and recombinases, suggesting their ability to quickly obtain genes to change functions. Analysis of antibiotic resistance genes revealed the presence of antibiotic resistant-integrons. Together with the surprising number of new plasmids identified, as well as the finding of transmission and modification events for plasmids in this work, we came to the suggestion that plasmids play a major role in genetic plasticity. Conclusion: This study reveals that the diversity of plasmids in human-associated microbes has been underestimated. With the decreasing cost of whole-genome sequencing, monitoring plasmids deserves increased attention in future surveillance efforts.
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Bactérias , Hemorroidas , Filogenia , Plasmídeos , Humanos , Plasmídeos/genética , Hemorroidas/microbiologia , Hemorroidas/genética , Bactérias/genética , Bactérias/isolamento & purificação , Sequenciamento Completo do Genoma , Masculino , Farmacorresistência Bacteriana Múltipla/genética , Feminino , AdultoRESUMO
Insomnia is a widespread health problem among adults, and it impairs cognitive control and emotional regulation functions. Stress and insomnia are positively correlated, and their vicious cycle has been widely reported. In this study, we explore the neural biomarkers of insomnia from the perspective of whole-brain functional connectivity and investigate the neural mechanisms underlying the association between stress and insomnia. The current study was conducted on a cross-sectional sample (N = 430). First, we investigated the correlation between perceived stress and insomnia. Second, we applied connectome-based predictive modeling (CPM) to determine the neuromarkers of insomnia. Finally, we explored the neural basis underlying the association between perceived stress and insomnia. A significant positive correlation was found between perceived stress and insomnia in the present research. Results of CPM revealed the following as the neural substrates supporting insomnia: the emotion regulation circuit involving repetitive negative thinking and the cognitive control circuit involving attention control. According to further results from mediation analysis, the frontoparietal network supporting cognitive emotion regulation is an important neural mechanism that maintains the correlation between stress and insomnia. The present study offers a profound insight into the alterations of brain activity related to insomnia, and it further investigates the neural underpinnings of the robust association between stress and insomnia. This study also opens new avenues for neural interventions to alleviate stress-related insomnia.
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The Agrobacterium-mediated transient expression system has been developed and applied to various plants as an alternative to stable transformation. However, its application in tomatoes is still limited due to low expression efficiency. In this study, we describe an improved vacuum-infiltration system that can be used in both tomato fruits and leaves. Notably, this study is the first report of vacuum infiltration in attached tomato fruits. The feasibility of the improved vacuum-infiltration system in Micro-Tom tomato was confirmed by various assays, including multiple fluorescent protein expression analysis, ß-glucuronidase activity analysis, and RUBY reporter visualization. Subsequently, the improved vacuum-infiltration system was successfully applied to tomato biotechnology research. Herein, a trichome-specific promoter in tomato was identified that can drive the directional synthesis of specific plant natural products (PNPs). Additionally, based on the assessment results of the improved vacuum-infiltration system, we obtained a flavonoid-rich tomato variety through the stable transformation of AmRosea and AmDelila. In a significant practical application, we successfully synthesized the high-value scutellarin in tomato, which provides an alternative route for the production of PNPs from plants. In addition, the improved vacuum-infiltration system has been demonstrated to be suitable for commercial tomato varieties ('Emerald' and 'Provence') as well. The improved vacuum-infiltration system not only speeds up fundamental and applied research in tomato but also offers an additional powerful tool for advancing tomato synthetic biology research.
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De novo lipogenesis (DNL), a hallmark of cancer, facilitates tumor growth and metastasis. Therapeutic drugs targeting DNL are being developed. However, how DNL is directly regulated in cancer remains largely unknown. Here, transcription factor sine oculis homeobox 1 (SIX1) is shown to directly increase the expression of DNL-related genes, including ATP citrate lyase (ACLY), fatty acid synthase (FASN), and stearoyl-CoA desaturase 1 (SCD1), via histone acetyltransferases amplified in breast cancer 1 (AIB1) and lysine acetyltransferase 7 ï¼HBO1/KAT7ï¼, thus promoting lipogenesis. SIX1 expression is regulated by insulin/lncRNA DGUOK-AS1/microRNA-145-5p axis, which also modulates DNL-related gene expression as well as DNL. The DGUOK-AS1/microRNA-145-5p/SIX1 axis regulates liver cancer cell proliferation, invasion, and metastasis in vitro and in vivo. In patients with liver cancer, SIX1 expression is positively correlated with DGUOK-AS1 and SCD1 expression and is negatively correlated with microRNA-145-5p expression. DGUOK-AS1 is a good predictor of prognosis. Thus, the DGUOK-AS1/microRNA-145-5p/SIX1 axis strongly links DNL to tumor growth and metastasis and may become an avenue for liver cancer therapeutic intervention.
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OBJECTIVES: To examine changes in technology-related errors (TREs), their manifestations and underlying mechanisms at 3 time points after the implementation of computerized provider order entry (CPOE) in an electronic health record; and evaluate the clinical decision support (CDS) available to mitigate the TREs at 5-years post-CPOE. MATERIALS AND METHODS: Prescribing errors (n = 1315) of moderate, major, or serious potential harm identified through review of 35 322 orders at 3 time points (immediately, 1-year, and 4-years post-CPOE) were assessed to identify TREs at a tertiary pediatric hospital. TREs were coded using the Technology-Related Error Mechanism classification. TRE rates, percentage of prescribing errors that were TREs, and mechanism rates were compared over time. Each TRE was tested in the CPOE 5-years post-implementation to assess the availability of CDS to mitigate the error. RESULTS: TREs accounted for 32.5% (n = 428) of prescribing errors; an adjusted rate of 1.49 TREs/100 orders (95% confidence interval [CI]: 1.06, 1.92). At 1-year post-CPOE, the rate of TREs was 40% lower than immediately post (incident rate ratio [IRR]: 0.60; 95% CI: 0.41, 0.89). However, at 4-years post, the TRE rate was not significantly different to baseline (IRR: 0.80; 95% CI: 0.59, 1.08). "New workflows required by the CPOE" was the most frequent TRE mechanism at all time points. CDS was available to mitigate 32.7% of TREs. DISCUSSION: In a pediatric setting, TREs persisted 4-years post-CPOE with no difference in the rate compared to immediately post-CPOE. CONCLUSION: Greater attention is required to address TREs to enhance the safety benefits of systems.
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The use of agricultural biomass-based fertilizers, and the release of feces into the environment leads to last-lasting pollution of antibiotic resistance genes that cannot be removed from waters via traditional methods, resulting in significant health threats. To solve this issue, an antibiotic resistance gene removal method was proposed and tested that used sequence-specific DNA-binding designer zinc finger proteins, which target an 18-bp DNA sequence for specific antibiotic resistance gene binding and removal. Targeting the sulfonamide-resistant sul1 gene, sul1-binding zinc-finger protein was designed, overexpressed, and purified. This protein showed specific binding with sul1 over tetA that do not have the targeted sequence. This protein was further immobilized on agarose-based resins to prepare a sul1-removal column. When loaded with 10â¯mg protein, this column can remove over 99â¯% sul1 in water, suggesting high efficiency. This work presents a new method attempting to eliminate environmental and health threats posed by antibiotic resistance genes.
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Dendritic cells (DCs) are critical mediators of antigen priming and T-cell activation. Zymogen granule protein 16 (ZG16) is demonstrated as an anti-oncogene in T-cell mediated antitumor immunity, but its effect on DCs is largely unknown. Herein, we wonder whether ZG16 affects the activation of DCs in pancreatic cancer. Firstly, the increased ZG16 expression was observed during the maturation of DCs derived from mouse bone marrow or human peripheral blood. Then, overexpression of ZG16 or exogenous introduction of recombinant ZG16 protein induced the expression of MHC II, CD86, CD84, and CCR7 on the surface of DCs, thereby facilitating the secretion of proinflammatory mediators IL-1ß, IL-6, TNF-α, and IL-12/p70, supporting the promoting effect of ZG16 on DC maturation. By establishing the subcutaneous and orthotopic mouse models of pancreatic cancer, we confirmed that intraperitoneal injection of recombinant ZG16 protein (Re-mZG16) could induce tumor regression by stimulating DC maturation and enhancing antitumor responses of CD4 + , CD8 + , PD-1 + , and Ctla4+ cells. Besides, Re-mZG16 in combination with gemcitabine showed a synergistic effect in the treatment of pancreatic cancer. Mechanistically, we demonstrated that ZG16 inhibited the ubiquitination and degradation of CD40, which depended on the lectin domain of ZG16. In conclusion, this study provided a novel insight into the role of ZG16-CD40 axis in DC-based immunotherapy for pancreatic cancer.
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OBJECTIVES: To compare the 2-year efficacy and safety of various anti-vascular endothelial growth factor (VEGF) regimens for neovascular age-related macular degeneration (nAMD). METHODS: A comprehensive search was performed on multiple electronic databases up to April 2023 and updated in June 2024, to identify relevant randomized controlled trials (RCTs). Key outcomes included the proportion of patients achieving a vision gain of ≥15 letters and maintaining stable vision (loss of <15 letters) in best-corrected visual acuity (BCVA), changes in mean BCVA from baseline, serious ocular adverse events (SAEs), adverse events leading to treatment discontinuation and any cause of death at 2 years. RESULTS: Nineteen trials with 12,654 patients and 25 treatment regimens were analyzed in the study. All anti-VEGF regimens showed superior efficacy compared to sham therapy. Specifically, faricimab 6 mg (4+up to Q16W) and ranibizumab 0.5 mg (2-week T&E) displayed top-level effect in vision gain. Bevacizumab 1.25 mg (2-week T&E) and aflibercept 2 mg (2-week T&E) demonstrated the most stable vision outcomes. Bevacizumab 1.25 mg (2-week T&E) and ranibizumab 0.5 mg (2-week T&E) exhibited the most pronounced mean BCVA improvement. Compared to sham therapy, the risk of SAEs was significantly higher for brolucizumab 6 mg (3 + Q12W/ Q8W) (RR = 6.04, 95% CI: 1.30-28.02) and PDS 100 mg/ml (Q24W) (RR = 10.95, 95% CI: 2.14-56.02), but not for other anti-VEGF regimens. CONCLUSIONS: Ranibizumab 0.5 mg (2-week T&E) emerges as a potentially optimal regimen for nAMD over a 2-year period. Future studies need to consider the impact of baseline characteristics on treatment outcomes.
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OBJECTIVE: Fetal venous system malformations frequently coincide with cardiac or extracardiac anomalies. This study explores our experience with an integrated fetal echocardiography approach and analyzes the characteristics and outcomes of fetal venous system disorders. MATERIALS AND METHODS: We conducted a retrospective study with 7048 pregnant women (7255 fetuses) who underwent complete two-dimensional (2D) fetal echocardiographic examinations. We primarily employed an integrated 2D approach. Three-/four-dimensional (3D/4D) spatiotemporal image correlation was supplemental. Fetal venous disorders were classified into 3 groups: cardinal (Group 1), umbilical and vitelline (Group 2), and pulmonary (Group 3) systems, based on embryological-anatomical considerations. Maternofetal data were recorded alongside imaging diagnoses. RESULTS: Congenital venous malformations were identified in 98 fetuses, yielding a prevalence of 1.35% (98/7255). Six participants had coexisting venous disorders from different groups. Group 1 included 48 fetuses with persistent left superior vena cava (LSVC) and 3 others (unidentified brachiocephalic vein, left inferior vena cava (IVC), and interrupted IVC with azygous continuation to SVC). Group 2 had 39 fetuses with persistent right umbilical vein and 7 with umbilical-portal-ductus venosus disorders. Group 3 had 7 fetuses with pulmonary venous return disorders. Group 2 showed the most favorable outcomes (alive and without neonatal death), while Group 3 exhibited the poorest. Associated cardiac defects were observed in 43.1% of Group 1, 8.7% of Group 2, and 57.1% of Group 3 (P < 0.001), displaying a broad spectrum of non-specific anomalies. Meanwhile, Group 2 had a greater occurrence of a single venous disorder (93.5%) compared to Group 1 (88.2%) and Group 3 (57.1%) (P = 0.020). CONCLUSION: Our approach offers an integrated strategy for assessing the fetal venous system during fetal echocardiography, providing multiple views to characterize venous anomalies. The presence of a fetal venous disorder may indicate the coexistence of more severe abnormalities, and the prognosis depends on associated anomalies or the venous disorders per se.
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Ultrassonografia Pré-Natal , Humanos , Feminino , Gravidez , Estudos Retrospectivos , Ultrassonografia Pré-Natal/métodos , Adulto , Ecocardiografia/métodos , Malformações Vasculares/diagnóstico por imagem , Malformações Vasculares/embriologia , Veias Umbilicais/diagnóstico por imagem , Veias Umbilicais/anormalidades , Veias Umbilicais/embriologia , Doenças Fetais/diagnóstico por imagem , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/embriologia , Relevância ClínicaRESUMO
Currently, as the largest family of E3 ubiquitin ligases, Skp1-Cullin 1-F-box (SCF) E3 ligase complexes have attracted extensive attention. Among SCF complexes, Skp2, ß-TrCP, and FBXW7 have undergone extensive research on their structures and functions. Previous studies suggest Skp2, ß-TrCP, and FBXW7 are overexpressed in numerous cancers. Thus, the SCF E3 ligase complex has become a significant target for the development of anti-cancer drugs. Over the past few decades, a variety of anti-tumor inhibitors targeting the SCF E3 ligase complex have been attempted. However, since almost none of the SCF E3 ligase inhibitors passed clinical trials, the design and synthesis of the new inhibitors are needed. Here, we will introduce the structure and function of Skp2, ß-TrCP, and FBXW7, their connections with cancer development, the relevant in vitro and in vivo activities, selectivity, structure-activity relationships, and the therapeutic or preventive application of small molecule inhibitors targeting these three F-box proteins reported in the patent (2010-present). This information will help develop drugs targeting the SCF E3 ubiquitin ligase, providing new strategies for future cancer treatments.
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Antineoplásicos , Desenho de Fármacos , Neoplasias , Humanos , Relação Estrutura-Atividade , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Patentes como Assunto , Animais , Proteínas Ligases SKP Culina F-Box/metabolismo , Proteínas Ligases SKP Culina F-Box/antagonistas & inibidores , Estrutura Molecular , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/síntese química , Ubiquitina-Proteína Ligases/antagonistas & inibidores , Ubiquitina-Proteína Ligases/metabolismo , Proteínas Quinases Associadas a Fase S/antagonistas & inibidores , Proteínas Quinases Associadas a Fase S/metabolismo , Proteína 7 com Repetições F-Box-WD/metabolismoRESUMO
The three-dimensional (3D) geometry of carotid atherosclerotic plaques is associated with multiple cardiovascular diseases. However, it is unknown if carotid plaques of different sizes are consistent in 3D geometry, with a lack of quantitative observation. We aim to evaluate the geometric consistency of carotid plaques using the correlations between multidimensional parameters. 42 cases with asymptomatic stenosis caused by atherosclerotic plaque in the carotid artery were included. Carotid plaques and calcifications were identified on computed tomography angiography images and 3D reconstructed. Multidimensional geometric parameters (length, surface area, volume, etc.) were measured on the reconstructed 3D structures. Linear and non-linear (power function) fittings were used to investigate the relationships between multidimensional parameters. The analysis was performed based on cases and plaques, respectively. Spearman rank correlation analysis, R-squared, and p-values were used to evaluate the significance of the relationship. Significant relationship was defined as R-squared >0.25 and p < 0.05. In total, 112 atherosclerotic plaques and 74 calcifications were extracted. In plaque-based analysis, significant correlations were widely observed between paired multidimensional parameters of carotid plaques, where non-linear fitting showed higher R-squared values. Plaque volume and surface area were significantly correlated with total volume and total surface area of intra-plaque calcifications. In subject-based analysis, triglycerides and total cholesterol were significantly correlated with carotid plaque size. There is a consistency in geometry among carotid atherosclerotic plaques of different sizes. The size of a carotid plaque is associated with the patient's lipid profile.
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Background: Pregnancy-related anemia presents a significant health concern for approximately 500 million women of reproductive age worldwide. To better prevent maternal disorders, it is essential to understand the impact of iron deficiency across different maternal disorders, regions, age groups, and subcategories. Methods: Based on the comprehensive maternal disorders data sourced from the 2019 Global Burden of Disease study, an investigation was carried out focusing on Disability-Adjusted Life Years (DALYs) associated with iron deficiency spanning the period from 1990 to 2019. In addition, Estimated Annual Percentage Changes (EAPCs) were computed for the duration of the study. Results: Our study indicates decreasing mortality rates and years of life lost due to maternal conditions related to iron deficiency, such as maternal hemorrhage, miscarriage, abortion, hypertensive disorders, and infections. However, mortality rates and years of life lost due to indirect and late maternal deaths, as well as deaths aggravated by HIV/AIDS, have increased in high socio-demographic index (SDI) regions, especially in North America. Moreover, the proportion of maternal deaths aggravated by HIV/AIDS due to iron deficiency is rising globally, especially in Southern Sub-Saharan Africa, Oceania, and Georgia. In addition, in the Maldives, the age-standardized DALYs for maternal disorders attributable to iron deficiency exhibited a notable decreasing trend, encompassing a range of conditions. Furthermore, there was a significant decrease in Disability-Adjusted Life Years rate for miscarriages and preterm births among women aged 15-49, with hypertensive disorders posing the highest burden among women aged 15-39. Conclusion: The burden of maternal disorders caused by iron deficiency is decreasing in most regions and subtypes, except for deaths aggravated by HIV/AIDS. By thoroughly understanding the details of how iron deficiency impacts the health of pregnant women, health policymakers, healthcare professionals, and researchers can more effectively pinpoint and address the root causes of inequalities in maternal health.
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Anemia Ferropriva , Anos de Vida Ajustados por Deficiência , Carga Global da Doença , Humanos , Feminino , Gravidez , Anemia Ferropriva/epidemiologia , Adulto , Mortalidade Materna , Saúde Global/estatística & dados numéricos , Complicações na Gravidez/epidemiologia , Adulto Jovem , Deficiências de Ferro , Adolescente , Anos de Vida Ajustados por Qualidade de VidaRESUMO
Enantioselective radical reactions mediated by TBADT have seldom been seen due to the inherent challenges. Herein, we disclose a new chiral hydrogen atom transfer (HAT) reagent that was generated easily from 8H-BINOL, potassium carbonate, and TBADT under irradiation. The new complex 8H-BINOL/DTs could be used as a chiral H donor. A series of azaarenes could be converted into the corresponding chiral compounds via radical addition followed by enantioselective HAT.