High-resolution X-ray luminescence extension imaging.

Current X-ray imaging technologies involving flat-panel detectors have difficulty in imaging three-dimensional objects because fabrication of large-area, flexible, silicon-based photodetectors on highly curved surfaces remains a challenge1-3. Here we demonstrate ultralong-lived X-ray trapping for flat-panel-free, high-resolution, three-dimensional imaging using a series of solution-processable, lanthanide-doped nanoscintillators. Corroborated by quantum mechanical simulations of defect formation and electronic structures, our experimental characterizations reveal that slow hopping of trapped electrons due to radiation-triggered anionic migration in host lattices can induce more than 30 days of persistent radioluminescence. We further demonstrate X-ray luminescence extension imaging with resolution greater than 20 line pairs per millimetre and optical memory longer than 15 days. These findings provide insight into mechanisms underlying X-ray energy conversion through enduring electron trapping and offer a paradigm to motivate future research in wearable X-ray detectors for patient-centred radiography and mammography, imaging-guided therapeutics, high-energy physics and deep learning in radiology.

Monocyte-derived SDF1 supports optic nerve regeneration and alters retinal ganglion cells' response to Pten deletion.

Although mammalian retinal ganglion cells (RGCs) normally cannot regenerate axons nor survive after optic nerve injury, this failure is partially reversed by inducing sterile inflammation in the eye. Infiltrative myeloid cells express the axogenic protein oncomodulin (Ocm) but additional, as-yet-unidentified, factors are also required. We show here that infiltrative macrophages express stromal cell­derived factor 1 (SDF1, CXCL12), which plays a central role in this regard. Among many growth factors tested in culture, only SDF1 enhances Ocm activity, an effect mediated through intracellular cyclic AMP (cAMP) elevation and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) activation. SDF1 deficiency in myeloid cells (CXCL12flx/flxLysM-Cre−/+ mice) or deletion of the SDF1 receptor CXCR4 in RGCs (intraocular AAV2-Cre in CXCR4flx/flx mice) or SDF1 antagonist AMD3100 greatly suppresses inflammation-induced regeneration and decreases RGC survival to baseline levels. Conversely, SDF1 induces optic nerve regeneration and RGC survival, and, when combined with Ocm/cAMP, SDF1 increases axon regeneration to levels similar to those induced by intraocular inflammation. In contrast to deletion of phosphatase and tensin homolog (Pten), which promotes regeneration selectively from αRGCs, SDF1 promotes regeneration from non-αRGCs and enables the latter cells to respond robustly to Pten deletion; however, SDF1 surprisingly diminishes the response of αRGCs to Pten deletion. When combined with inflammation and Pten deletion, SDF1 enables many RGCs to regenerate axons the entire length of the optic nerve. Thus, SDF1 complements the effects of Ocm in mediating inflammation-induced regeneration and enables different RGC subtypes to respond to Pten deletion.

Visualization of Biomolecular Radiation Damage at the Single-Particle Level Using Lanthanide-Sensitized DNA Origami.

Precise monitoring of biomolecular radiation damage is crucial for understanding X-ray-induced cell injury and improving the accuracy of clinical radiotherapy. We present the design and performance of lanthanide-DNA-origami nanodosimeters for directly visualizing radiation damage at the single-particle level. Lanthanide ions (Tb3+ or Eu3+) coordinated with DNA origami nanosensors enhance the sensitivity of X-ray irradiation. Atomic force microscopy (AFM) revealed morphological changes in Eu3+-sensitized DNA origami upon X-ray irradiation, indicating damage caused by ionization-generated electrons and free radicals. We further demonstrated the practical applicability of Eu3+-DNA-origami integrated chips in precisely monitoring radiation-mediated cancer radiotherapy. Quantitative results showed consistent trends with flow cytometry and histological examination under comparable X-ray irradiation doses, providing an affordable and user-friendly visualization tool for preclinical applications. These findings provide new insights into the impact of heavy metals on radiation-induced biomolecular damage and pave the way for future research in developing nanoscale radiation sensors for precise clinical radiography.

Association between estimated pulse wave velocity and the risk of mortality in patients with subarachnoid hemorrhage: a retrospective cohort study based on the MIMIC database.

BACKGROUND: The estimated pulse wave velocity (ePWV) is a recently developed, simple and useful tool to measure arterial stiffness and to predict long-term cardiovascular mortality. However, the association of ePWV with mortality risk in patients with subarachnoid hemorrhage (SAH) is unclear. Herein, this study aims to assess the potential prediction value of ePWV on short- and long-term mortality of SAH patients. METHODS: Data of adult patients with no traumatic SAH were extracted from the Medical Information Mart for Intensive Care (MIMIC) III and IV database in this retrospective cohort study. Weighted univariate and multivariable Cox regression analyses were used to explore the associations of ePWV levels with 30-day mortality and 1-year mortality in SAH patients. The evaluation indexes were hazard ratios (HRs) and 95% confidence intervals (CIs). In addition, subgroup analyses of age, the sequential organ failure assessment (SOFA) score, surgery, atrial fibrillation (AF), renal failure (RF), hepatic diseases, chronic obstructive pulmonary disease (COPD), sepsis, hypertension, and diabetes mellitus (DM) were also performed. RESULTS: Among 1,481 eligible patients, 339 died within 30 days and 435 died within 1 year. After adjusting for covariates, ePWV ≥ 12.10 was associated with higher risk of both 30-day mortality (HR = 1.77, 95%CI: 1.17-2.67) and 1-year mortality (HR = 1.97, 95%CI: 1.36-2.85), compared to ePWV < 10.12. The receiver operator characteristic (ROC) curves showed that compared to single SOFA score, ePWV combined with SOFA score had a relative superior predictive performance on both 30-day mortality and 1-year mortality, with the area under the curves (AUCs) of 0.740 vs. 0.664 and 0.754 vs. 0.658. This positive relationship between ePWV and mortality risk was also found in age ≥ 65 years old, SOFA score < 2, non-surgery, non-hepatic diseases, non-COPD, non-hypertension, non-DM, and sepsis subgroups. CONCLUSION: Baseline ePWV level may have potential prediction value on short- and long-term mortality in SAH patients. However, the application of ePWV in SAH prognosis needs further clarification.

Preparation of a high-performance H2S gas sensor based on CuO/Co3O4composite derived from bimetallic MOF.

The bimetallic metal-organic frameworks (MOFs), Cu/Co-MOF, was synthesized through a solvothermal method and calcined to obtain CuO/Co3O4composites. By adjusting the molar ratio between Cu and Co ions, a composite material of CuO/Co3O4(Cu:Co = 1:1) was developed and showed excellent sensing capabilities, and the response reached as high as 196.3 for 10 ppm H2S detection. Furthermore, the optimal operating temperature as low as 40 °C was found. In comparison with the sensors prepared by pristine CuO and pristine Co3O4, the sensor based on CuO/Co3O4composite exhibited a significant response. Additionally, the sensor can detect H2S gas down to 300 ppb. The gas sensing mechanism is discussed in depth from the perspective of p-p heterojunction formation between the p-type CuO and p-type Co3O4. The as-prepared CuO/Co3O4composite-based sensor is expected to find practical application in the low-power monitoring of H2S.

Room-temperature highly sensitive triethylamine detection by few-layer Nb2CTxMXene nanosheets.

MXene, a class of two-dimensional materials that are emerging as rising stars in the field of materials, are receiving much attention in sensing. Ti3C2TxMXene, the most maturely researched MXene, is widely used in energy, biomedical, laser, and microwave shielding applications and has also been expanded to gas sensing and wearable electronics applications. Compared with Ti3C2Tx, Nb2CTxMXene is more difficult to etch and has higher resistances at room temperature; so, few studies have been reported on their use in the sensing field. Based on the preparation of few-layer Nb2CTxMXene by intercalation, this study thoroughly examined their gas-sensing properties. The successfully prepared few-layer Nb2CTxshowed good selectivity and high sensitivity to triethylamine at room temperature, with response values up to 47.2% for 50 ppm triethylamine and short response/recovery time (22/20 s). This study opens an important path for the design of novel Nb-based MXene sensors for triethylamine gas detection.

Theoretical investigation of Janus Ti2BST (T = O, Se) monolayers as anode materials for Na/K-ion batteries.

The structures, stability, and electrochemical performances of Janus Ti2BST (T = O, Se) monolayers as anode materials for Na/K-ion batteries (NIBs/KIBs) are investigated by first-principles calculations. The results demonstrate that Ti2BST monolayers are mechanically, dynamically, and thermally stable. The electronic structures display good conductivity. Moreover, the low diffusion barriers of 0.107/0.039 eV (0.111/0.063 eV) for Na/K indicate that the Ti2BSO (Ti2BSSe) monolayer has excellent rate performance for NIBs/KIBs. Low average open circuit voltages (OCVs) (0.322-0.439 V) can produce a high voltage in NIBs/KIBs. Meanwhile, little structural changes during charge/discharge ensure great cycle stability. Especially, the Ti2BSO monolayer has a high theoretical capacity of 691.64/537.75 mA h g-1 for NIBs/KIBs. The outstanding performances demonstrate that the Ti2BST monolayers are potential anode materials for NIBs/KIBs.

Chemokine CCL5 promotes robust optic nerve regeneration and mediates many of the effects of CNTF gene therapy.

Ciliary neurotrophic factor (CNTF) is a leading therapeutic candidate for several ocular diseases and induces optic nerve regeneration in animal models. Paradoxically, however, although CNTF gene therapy promotes extensive regeneration, recombinant CNTF (rCNTF) has little effect. Because intraocular viral vectors induce inflammation, and because CNTF is an immune modulator, we investigated whether CNTF gene therapy acts indirectly through other immune mediators. The beneficial effects of CNTF gene therapy remained unchanged after deleting CNTF receptor alpha (CNTFRα) in retinal ganglion cells (RGCs), the projection neurons of the retina, but were diminished by depleting neutrophils or by genetically suppressing monocyte infiltration. CNTF gene therapy increased expression of C-C motif chemokine ligand 5 (CCL5) in immune cells and retinal glia, and recombinant CCL5 induced extensive axon regeneration. Conversely, CRISPR-mediated knockdown of the cognate receptor (CCR5) in RGCs or treating wild-type mice with a CCR5 antagonist repressed the effects of CNTF gene therapy. Thus, CCL5 is a previously unrecognized, potent activator of optic nerve regeneration and mediates many of the effects of CNTF gene therapy.

Childhood adversity, perceived social support, and depressive symptoms among pre-abortion Chinese women.

BACKGROUND: Unintended (unwanted) pregnancy is a sexual and reproductive health issue with psychosocial consequences for the individual, their family, and society. However, the relationship between social support and related mental health issues, like depression and the effects of childhood adversity, is poorly studied. This study aims to explore the connections between childhood adversity, perceived social support, and depressive symptoms in pre-abortion women (women who have decided to have an abortion) in a clinical setting, based on the common risk factor approach and social support theory. METHODS: A total of 299 pre-abortion Chinese women 18-45 years were recruited in a hospital in Shantou, China. Hierarchical linear regression analyses were employed to examine the relative effects of childhood adversity and sources of social support on depressive symptoms, controlling for sociodemographic influences. RESULTS: The results show that 37.2 percent of participants reported at least one adverse experience in childhood. More than half of the respondents were at risk for depression. Results of regression analysis showed that childhood adversities were negatively associated with depressive symptoms before sources of social support were entered into the model. However, when the sources of perceived social support were added, the effect of childhood adversity was not significant. Perceived social support explained the additional 15 percent variance in depressive symptoms. Additionally, being married (ß = -.12, p < .05) and number of siblings (ß = .13, p < .05) were significantly related to depressive symptoms. DISCUSSION: Pre-abortion women are at risk of mental health problems. Peer and familial social supports can alleviate the influence of childhood adversity on depression among pre-abortion Chinese women. Strengthening the role of various sources of social support can help to improve the mental health conditions of pre-abortion women.

Effects of terrestrial dissolved organic matter on the growth, photosynthesis and colonial morphology of Microcystis aeruginosa at different levels of iron.

Terrestrial dissolved organic matter (tDOM) holds great promise for controlling cyanobacteria blooms through watershed management. To identify tDOM that could inhibit the growth, photosynthesis and colony formation, unicellular Microcystis aeruginosa Kützing (FACHB-469) was cultivated and treated with varying concentrations of gallic acid, proline and tea polyphenols at different levels of iron. The results indicated that gallic acid and tea polyphenols could inhibit Microcystis growth by suppressing photosynthesis and colony formation by reducing extracellular polysaccharides (EPS) secretion. However, proline had no significant effect on the growth, photosynthesis, colony size and EPS content of Microcystis. Transcriptome analysis showed Microcystis may optimize the internal energy transfer mode of photosynthesis through the change of phycobilisome at different levels of iron. In addition, Microcystis adapted to different iron concentration environments by regulating the expression of genes associated with iron uptake and transport. These findings suggest that the effects of plant species on algal blooms should be considered in reforestation of watershed. This consideration necessitates finding a balance between the costs and benefits of controlling cyanobacteria blooms using tDOM.

Fraxetin pretreatment alleviates cisplatin-induced kidney injury by antagonizing autophagy and apoptosis via mTORC1 activation.

Cisplatin-induced kidney injury (CKI) is a common complication of chemotherapy. Fraxetin, derived from Fraxinus bungeana A. DC. bark, has antioxidant, anti-inflammatory, and anti-fibrotic effects. This study aims to investigate fraxetin's effects on CKI and its underlying mechanism in vivo and in vitro. Tubular epithelial cells (TECs) and mice were exposed to cisplatin with and without fraxetin preconditioning assess fraxetin's role in CKI. TECs autophagy was observed using transmission electron microscopy. Apoptosis levels in animal tissues were measured using TUNEL staining. The protective mechanism of fraxetin was explored through pharmacological and genetic regulation of mTORC1. Molecular docking was used to identify potential binding sites between fraxetin and mTORC1. The results indicated that fraxetin pretreatment reduced cisplatin-induced kidney injury in a time- and concentration-dependent way. Fraxetin also decreased autophagy in TECs, as observed through electron microscopy. Tissue staining confirmed that fraxetin pretreatment significantly reduced cisplatin-induced apoptosis. Inhibition of mTORC1 using rapamycin or siRNA reversed the protective effects of fraxetin on apoptosis and autophagy in cisplatin-treated TECs, while activation of mTORC1 enhanced fraxetin's protective effect. Molecular docking analysis revealed that fraxetin can bind to HEAT-repeats binding site on mTORC1 protein. In  summary, fraxetin pretreatment alleviates CKI by antagonizing autophagy and apoptosis via mTORC1 activation. This provides evidence for the potential therapeutic application of fraxetin in CKI.

The effects of adenoid hypertrophy and oral breathing on maxillofacial development: a review of the literature.

According to modern epidemiological surveys, the prevalence of adenoid hypertrophy in children and adolescents ranges from 42% to 70%. Adenoid hypertrophy can lead to airway obstruction; thus forces a child to breathe through their mouth, thus affecting the normal development of the dental and maxillofacial area, and can lead to malocclusion. Long-term mouth breathing can cause sagittal, vertical and lateral changes in the maxillofacial area. In this article, we review the current research status relating to the association between adenoid hypertrophy, oral breathing and maxillofacial growth and development in children and adolescents. We also discuss the personalized formulation of treatment plans.

Probing Energy-Funneling Kinetics in Nanocrystal Sublattices for Superior X-Ray Imaging.

Long-lasting radioluminescence scintillators have recently attracted substantial attention from both research and industrial communities, primarily due to their distinctive capabilities of converting and storing X-ray energy. However, determination of energy-conversion kinetics in these nanocrystals remains unexplored. Here we present a strategy to probe and unveil energy-funneling kinetics in NaLuF4:Mn2+/Gd3+ nanocrystal sublattices through Gd3+-driven microenvironment engineering and Mn2+-mediated radioluminescence profiling. Our photophysical studies reveal effective control of energy-funneling kinetics and demonstrate the tunability of electron trap depth ranging from 0.66 to 0.96 eV, with the corresponding trap density varying between 2.38×105 and 1.34×107 cm-3. This enables controlled release of captured electrons over durations spanning from seconds to 30 days. It allows tailorable emission wavelength within the range of 520-580 nm and fine-tuning of thermally-stimulated temperature between 313-403 K. We further utilize these scintillators to fabricate high-density, large-area scintillation screens that exhibit a 6-fold improvement in X-ray sensitivity, 22 lp/mm high-resolution X-ray imaging, and a 30-day-long optical memory. This enables high-contrast imaging of injured mice through fast thermally-stimulated radioluminescence readout. These findings offer new insights into the correlation of radioluminescence dynamics with energy-funneling kinetics, thereby contributing to the advancement of high-energy nanophotonic applications.

The effects of the coronavirus disease pandemic on intravenous thrombolytic therapy among patients with acute ischemic stroke in Dalian, China.

BACKGROUND: We investigated the influence of the coronavirus disease 2019 (COVID-19) pandemic on the number of patients with acute ischemic stroke who received intravenous thrombolytic therapy (ITT) in Dalian, China, in 2020. METHODS: This retrospective descriptive study, conducted from February 1, 2020, to August 31, 2020, examined 13 hospitals in Dalian that participated in the "stroke emergency map". To use this "stroke emergency map" of China, patients followed the official "Stroke Map" WeChat account and dialed 120 for emergency medical services. We analyzed the number of patients with acute ischemic stroke who underwent ITT. In particular, we examined the onset-to-door time (ODT), door-to-needle time (DNT), onset-to-needle time (ONT), mode of transportation to the hospital, and National Institutes of Health Stroke Scale (NIHSS) scores before and after ITT. Data were collected for the aforementioned period and compared with the 2021 baseline data from the same time of year. The Mann‒Whitney U test was performed for data analysis. RESULTS: Compared with the data from 2020, the number of patients with acute ischemic stroke who underwent ITT increased (from 735 to 1719 cases) in 2021, but the DNT decreased (from 59 to 45 min; P = 0.002). Moreover, 83.9% of patients in 2020 presented to the hospital without ambulance transport, compared to 81.1% of patients in the 2021 non-COVID-19 pandemic period. Patients with NIHSS scores of 6-14 were more likely to call an ambulance for transport to the hospital than to transport themselves to the emergency department. CONCLUSIONS: During the 2020 COVID-19 pandemic, the DNT was prolonged as a result of strengthened fever surveillance. In 2021, the number of patients with acute ischemic stroke who underwent ITT increased compared to the previous year. Notably, the growth in the number of patients with acute ischemic stroke who underwent ITT benefited from both the "stroke emergency map" of China and the "green channel," a novel treatment approach that focuses on the rational design of the rescue process. TRIAL REGISTRATION: Our study was a retrospective descriptive study, not a clinical trial, thus we did not have to register for clinical trials.

Activity engagement and cognitive function among chinese older adults: moderating roles of gender and age.

BACKGROUND: Many studies have found that engaging in activities, including physical exercise, social interaction, and cognitive training, is beneficial for preventing cognitive decline among older adults; however, the demographic differences in the association between activity engagement and cognitive functions remain understudied. This study investigates: (a) the influence of activity engagement on cognitive functions among Chinese older adults, and (b) the moderating roles of age and gender in these associations . METHODS: The data were derived from the China Health and Retirement Longitudinal Study in 2018, which included 9803 participants aged 60 or older. A multiple regression model was used to test the study hypotheses. RESULTS: Engaging in physical activity (b = 1.578, p < .001), social interaction (b = 1.199, p < .001), and cognitive activity (b = 1.468, p < .001) was positively associated with cognitive functions, whereas the effect of volunteer activities on cognitive functions was not significant (b = -.167, p = .390). Light- and moderate-intensity activities were beneficial for cognition (light: b = .847, p < .001; moderate: b = 1.189, p < .001), but vigorous-intensity activity was negatively related to cognition (b = -.767, p < .001). In addition, women and participants with advanced age appeared to benefit more from cognitive activities than their male and younger counterparts, respectively (gender: b = 1.217, p = .002; age: b = .086, p = .004). The adverse effects of vigorous-intensity activities (including agricultural work) on cognitive health were stronger for women and younger participants (gender: b = -1.472, p < .001; age: b = .115, p < .001). The protective effects of moderate-intensity activities on people's cognition increased with increasing age (b = .055, p = .012). CONCLUSIONS: The findings indicate that participating in physical, social, and cognitive activities can help older adults to maintain cognitive health. They suggest that older adults should select activities while considering activity intensity and their individual characteristics.

Does False Lumen Thrombosis Lead to Better Outcomes in Patients with Aortic Dissection: A Meta-Analysis and Systematic Review.

OBJECTIVES: For a long time, the association of the false lumen status and the outcomes of patients suffering from aortic dissection has been unclear, so this review article aims to study whether the unobstructed of the false lumen is related to the outcome of patients suffering from aortic dissection. METHODS: We performed this systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta Analyzes Protocols (PRISMA) statement 2009 and registered with PROSPERO (CRD42022381869). We searched PubMed, the Cochrane library, Web of Science and Embase to collect potential studies. The Newcastle-Ottawa Scale was used to assess the quality of the included studies. The main outcome is long-term survival. Data included in the study were summarized using the risk ratio or mean difference and 95% confidence interval. RESULTS: There were 16 trials, 2829 patients in total, with a mean age of 62.1 years. Compared with completely thrombosed false lumen, patent group has better long-term survival (risk ratio (RR), 0.88; 95% CI, 0.79 to 0.97; p = 0.01; I2 = 58%) and smaller yearly aortic growth rate (mean difference (MD), 1.03; 95% CI, 0.23 to 1.82; p = 0.01; I2 = 98%). In addition, patients with a patent false lumen had a lower risk of aortic event (RR, 0.81; 95% CI, 0.68 to 0.97; p = 0.02; I2 = 37%), but higher risk of aortic rupture (RR, 7.02; 95% CI, 2.55 to 19.3; p = 0.0002; I2 = 0) and hospital death (RR, 2.72; 95% CI, 1.45 to 5.08; p = 0.002; I2 = 0). CONCLUSION: Completely thrombosed of the false lumen is more beneficial to the long-term survival of patients with aortic dissection. And the risk of aortic rupture and hospital death in patients with patent false lumen is 7 times and 3 times that of patients with complete thrombosed false lumen. It is expected to provide individualized medical care for different types of patients according to different false lumen status to minimize death and related complications.

Inflammatory Mediators of Axon Regeneration in the Central and Peripheral Nervous Systems.

Although most pathways in the mature central nervous system cannot regenerate when injured, research beginning in the late 20th century has led to discoveries that may help reverse this situation. Here, we highlight research in recent years from our laboratory identifying oncomodulin (Ocm), stromal cell-derived factor (SDF)-1, and chemokine CCL5 as growth factors expressed by cells of the innate immune system that promote axon regeneration in the injured optic nerve and elsewhere in the central and peripheral nervous systems. We also review the role of ArmC10, a newly discovered Ocm receptor, in mediating many of these effects, and the synergy between inflammation-derived growth factors and complementary strategies to promote regeneration, including deleting genes encoding cell-intrinsic suppressors of axon growth, manipulating transcription factors that suppress or promote the expression of growth-related genes, and manipulating cell-extrinsic suppressors of axon growth. In some cases, combinatorial strategies have led to unprecedented levels of nerve regeneration. The identification of some similar mechanisms in human neurons offers hope that key discoveries made in animal models may eventually lead to treatments to improve outcomes after neurological damage in patients.

The effect of orthodontic pain on dental anxiety: a review.

Dental Anxiety constitutes a series of signs of sympathetic hyperfunction that arises during a dental visit. Orthodontic pain is a common reaction in children and adults that can increase dental anxiety and affect orthodontic outcomes. Both malocclusion and orthodontic pain negatively affect quality of life. Dental anxiety and orthodontic pain have different contributing factors, and the prevalence of malocclusion and dental anxiety varies. Different methods have been proposed for the classification of the dental anxiety scales and orthodontic pain as a first approach in the treatment process. The objective of this literature review was to discuss the effect of orthodontic pain on dental anxietyand to explore ways to address dental anxietyin children and adultsto reduce negative effects on quality of life. This review not only analyses the prevalence and etiology of dental anxiety, the characteristics and influencing factors of orthodontic pain; but also introduces how dental anxiety and orthodontic pain are diagnosed, and proposes some treatment options. The occurrence of malocclusion has recently risen in children and adults, and the negative effects of orthodontic pain and dental anxiety have been explored in literature. Therefore, this review attempts to provide a critical analysis of dental anxiety and orthodontic pain, to attract the attention of orthodontists and provide a framework for further exploration of effective treatment solutions.

Contribution of CYP19A1, CYP1A1, and CYP1A2 polymorphisms in coronary heart disease risk among the Chinese Han population.

The previous study has pointed to that endogenous CYP metabolites play an important role in the pathogenesis of coronary heart disease (CHD). The study aimed to identify the association of CYP19A1, CYP1A1, and CYP1A2 polymorphisms with CHD susceptibility in a Chinese Han population. A total of 960 genetically unrelated participants consist of 480 CHD patients and 480 healthy controls were enrolled. Nine SNPs in CYP19A1, CYP1A1, and CYP1A2 were randomly selected and genotyped using the Agena MassARRAY platform. Logistic regression analysis was used for the relationship between selected SNPs and CHD susceptibility by calculating odds ratios (OR) with 95% confidence intervals (CI) adjusted for age and gender. The distribution of clinical characteristics in different genotypes was evaluated by one-way analysis of variance (ANOVA). CYP1A2 rs2470890 TT genotype had a higher CHD risk compared with CC genotype (OR = 3.06, p = 0.032) or CC-CT genotype (OR = 3.04, p = 0.033). Moreover, the contribution of CYP19A1 and CYP1A2 polymorphisms to CHD susceptibility was associated with age, gender, and clinical phenotypes (course of the disease and Gensini score). Besides, CYP1A2 rs762551 was related to serum levels of red blood cell, triglyceride, total cholesterol, and low-density lipoprotein cholesterol (LDL-C, p < 0.05). Our findings provided scientific evidence about CYP19A1, CYP1A1, and CYP1A2 polymorphisms on CHD incidence.

Structural basis of indisulam-mediated RBM39 recruitment to DCAF15 E3 ligase complex.

The anticancer agent indisulam inhibits cell proliferation by causing degradation of RBM39, an essential mRNA splicing factor. Indisulam promotes an interaction between RBM39 and the DCAF15 E3 ligase substrate receptor, leading to RBM39 ubiquitination and proteasome-mediated degradation. To delineate the precise mechanism by which indisulam mediates the DCAF15-RBM39 interaction, we solved the DCAF15-DDB1-DDA1-indisulam-RBM39(RRM2) complex structure to a resolution of 2.3 Å. DCAF15 has a distinct topology that embraces the RBM39(RRM2) domain largely via non-polar interactions, and indisulam binds between DCAF15 and RBM39(RRM2), coordinating additional interactions between the two proteins. Studies with RBM39 point mutants and indisulam analogs validated the structural model and defined the RBM39 α-helical degron motif. The degron is found only in RBM23 and RBM39, and only these proteins were detectably downregulated in indisulam-treated HCT116 cells. This work further explains how indisulam induces RBM39 degradation and defines the challenge of harnessing DCAF15 to degrade additional targets.