Antiplatelet therapy after coronary artery bypass surgery: five year follow-up of randomised DACAB trial.

OBJECTIVE: To assess the effect of different antiplatelet strategies on clinical outcomes after coronary artery bypass grafting. DESIGN: Five year follow-up of randomised Different Antiplatelet Therapy Strategy After Coronary Artery Bypass Grafting (DACAB) trial. SETTING: Six tertiary hospitals in China; enrolment between July 2014 and November 2015; completion of five year follow-up from August 2019 to June 2021. PARTICIPANTS: 500 patients aged 18-80 years (including 91 (18.2%) women) who had elective coronary artery bypass grafting surgery and completed the DACAB trial. INTERVENTIONS: Patients were randomised 1:1:1 to ticagrelor 90 mg twice daily plus aspirin 100 mg once daily (dual antiplatelet therapy; n=168), ticagrelor monotherapy 90 mg twice daily (n=166), or aspirin monotherapy 100 mg once daily (n=166) for one year after surgery. After the first year, antiplatelet therapy was prescribed according to standard of care by treating physicians. MAIN OUTCOME MEASURES: The primary outcome was major adverse cardiovascular events (a composite of all cause death, myocardial infarction, stroke, and coronary revascularisation), analysed using the intention-to-treat principle. Time-to-event analysis was used to compare the risk between treatment groups. Multiple post hoc sensitivity analyses examined the robustness of the findings. RESULTS: Follow-up at five years for major adverse cardiovascular events was completed for 477 (95.4%) of 500 patients; 148 patients had major adverse cardiovascular events, including 39 in the dual antiplatelet therapy group, 54 in the ticagrelor monotherapy group, and 55 in the aspirin monotherapy group. Risk of major adverse cardiovascular events at five years was significantly lower with dual antiplatelet therapy versus aspirin monotherapy (22.6% v 29.9%; hazard ratio 0.65, 95% confidence interval 0.43 to 0.99; P=0.04) and versus ticagrelor monotherapy (22.6% v 32.9%; 0.66, 0.44 to 1.00; P=0.05). Results were consistent in all sensitivity analyses. CONCLUSIONS: Treatment with ticagrelor dual antiplatelet therapy for one year after surgery reduced the risk of major adverse cardiovascular events at five years after coronary artery bypass grafting compared with aspirin monotherapy or ticagrelor monotherapy. TRIAL REGISTRATION: NCT03987373ClinicalTrials.gov NCT03987373.

Modification of Risk for All-Cause and Cardiovascular Disease-Related Mortality with Changes in the Body Mass Index in Older Individuals: A Population-Based Cohort Study.

INTRODUCTION: Existing evidence evaluating the impact of change in body mass index (BMI) on the risk of all-cause and cardiovascular disease (CVD)-related mortality in older people is limited and inconsistent. This population-based cohort study evaluated the association of changes in BMI over time with all-cause and CVD-related mortality in older adults. METHODS: We recruited 55,351 adults aged over 65 years between 2006 and 2011 from Taipei Elderly Health Examination Program who underwent repeated annual health examinations at 3.2-year intervals and were followed up for mortality over 5.5 years. Cox proportional hazard and Fine-Gray sub-distribution hazard models with death from non-CVD causes as the competing risk were used to determine the impact of changes in BMI status on the risk of all-cause or CVD-related mortality, respectively. RESULTS: Over 227,967 person-years of follow-up, 4,054 participants died, including 940 (23.2%) CVD-related deaths. After adjusting for other covariates, >10% decrease in BMI was significantly associated with a higher risk of all-cause (adjusted hazard ratio [AHR] = 1.93; 95% confidence interval [CI]: 1.74-2.13) and CVD-related mortality (AHR = 1.96; 95% CI: 1.60-2.40), compared with stable BMI. Sensitivity analysis showed that a >10% decrease in BMI was significantly associated with a high risk of all-cause and CVD-related mortality in participants with normal weight, underweight, overweight, or obesity at baseline. CONCLUSION: Older adults with >10% decrease in BMI are at high risk of all-cause and CVD-related mortality. Our findings suggest that older individuals experiencing a substantial reduction in BMI should undergo a thorough evaluation to minimize the risks associated with mortality.

Surgical treatment of atrial fibrillation in mitral valve surgery: a narrative review.

Background and Objective: Atrial fibrillation (AF) is one of the most common arrhythmias in clinical practice, which leads to cardiac decompensation, cardiovascular and cerebrovascular infarction, and other thromboembolic diseases. AF is one of the most common comorbidities of valvular heart disease, especially in mitral valve disease. At the time of their mitral valve surgery, 20-42% of patients have AF. It is beneficial to maintain postoperative sinus rhythm and minimize complications when AF surgery is performed concurrently with mitral valve surgery. This review describes the surgical management of AF in mitral valve surgery, including AF surgical route, surgical ablation technology and surgical approaches. The aim of this review is to enable more patients with AF to receive more appropriate and individualised treatment. Methods: A narrative review was conducted on the literature on PubMed, Embase including all relevant studies published until November 2023. Key Content and Findings: This review focuses on the surgical management of AF during mitral valve surgery, including AF surgical route, surgical ablation technology and surgical approaches. Conclusions: Mitral valve surgery combined with AF surgery facilitates the maintenance of postoperative sinus rhythm in patients, reduces the risk of postoperative stroke, and improves survival. Advances in ablation technology have reduced the difficulty of the procedure, making it possible for more patients to undergo surgical ablation. In the future, it will be possible to tailor specific lesion sets and ablation modalities for individual patients. This would make surgical treatment of AF more effective and applicable to a larger population of patients with AF and mitral valve disease.

Development of neuromodulation for atrial fibrillation: a narrative review.

Background and Objective: Atrial fibrillation (AF) is a prevalent clinical arrhythmia with a high incidence of disability and mortality. Autonomic nervous system (ANS) plays a crucial role in the onset and persistence of AF, and can lead to electrophysiological changes and alterations in atrial structure. Both animal models and clinical findings suggest that parasympathetic and sympathetic activity within the cardiac ANS could induce atrial remodeling and AF. Remodeling of the cardiac autonomic nerves is a significant structural basis for promoting AF. Given the challenges faced by conventional pharmacological and atrial ablation techniques in the treatment of AF, increasing attention has been paid to autonomic intervention strategies for AF. Current research has demonstrated that the frequency and severity of AF episodes can be significantly reduced by modulating the activity of ANS. ANS neuromodulation is expected to lead more effective and personalized treatment options for patients with AF. The objective of this review is to provide a broader perspective for future related studies by reviewing preclinical and clinical studies of neuromodulation methods for the treatment of AF, searching for relevant approaches to treat AF, as well as identifying the strengths and weaknesses demonstrated by current relevant studies, and providing researchers with a broader overview of the latest neurological treatments for AF. Methods: A narrative review was conducted on the literature on PubMed, WanFang data, and Google Scholar, including all relevant studies published until November 2023. Key Content and Findings: In this review, we delve into the innervation of cardiac autonomic nerves, the role of the ANS in the development and maintenance of AF, and the current neuromodulation methods for AF treatment. These methods include stellate ganglion (SG) resection or ablation, vagus nerve stimulation (VNS), thoracic subcutaneous nerve stimulation (ScNS), renal denervation (RDN) therapy, ganglionated plexus (GP) ablation, and epicardial botulinum toxin or CaCl2 injection. More and more research suggests that neuromodulation methods for the treatment of AF have broad prospects. Conclusions: ANS plays a crucial role in AF development and maintenance through cardiac autonomic nerve remodeling. Modulating ANS activity can significantly reduce AF frequency and severity, offering more personalized treatment options. Current research on autonomic interventions for AF shows promise for more effective and personalized treatments.

The traditional Chinese version of the Geriatric Anxiety Inventory: Psychometric properties and cutoff point for detecting anxiety.

The study aimed to translate the Geriatric Anxiety Inventory into traditional Chinese (GAI-TC), examine its psychometric properties, and identify the optimal cutoff point. This research recruited 337 older adults from two community activity centers. Structured questionnaires were used, including demographic information and characteristics, the GAI-TC, and the State-Trait Anxiety Inventory (STAI). Cronbach's α of the GAI-TC was 0.93. The intraclass correlation coefficient was 0.90. The content validity index was 1.0. An exploratory factor analysis revealed that three factors in the GAI-TC, including cognition anxiety, impact of anxiety, and somatic anxiety, explained 59.46 % of the variance. The criterion-related validity showed a significant positive correlation between the GAI-TC and STAI, with an optimal cutoff of 9/10 for detecting anxiety in older persons living in the community. The GAI-TC had good reliability and validity and can provide professionals with a tool for the early identification of anxiety among older adults.

Diagnostic ability of macular nerve fiber layer thickness measured by swept-source optical coherence tomography in preperimetric glaucoma.

BACKGROUND: We evaluated the diagnostic ability of macula retinal nerve fiber layer (mRNFL) thickness in preperimetric glaucoma (PPG) patients. METHODS: This prospective study included 83 patients with PPG and 83 age- and refractive error-matched normal control subjects. PPG was defined as a localized RNFL defect corresponding to glaucomatous optic disc changes with a normal visual field test. We used spectral-domain (SD) optical coherence tomography (OCT) to measure the circumpapillary RNFL (cpRNFL) thickness and macular ganglion cell-inner plexiform layer (GCIPL) thickness. Swept-source (SS) OCT was used to measure cpRNFL thickness, macular ganglion cell layer + inner plexiform layer (IPL) thickness (GCL+), and macular ganglion cell layer + IPL+ mRNFL thickness (GCL++). The mRNFL thickness was defined as GCL++ minus GCL+. To evaluate the diagnostic power of each parameter, the area under the receiver operating characteristics curve (AUROC) was analyzed to differentiate PPG from the normal groups. RESULTS: Using SD-OCT, all GCIPL parameters and most cpRNFL parameters, except at the nasal and temporal quadrant, were significantly lower in PPG versus normal controls. PPG eyes had significantly smaller values than normal controls for all cpRNFL and GCL parameters measured by SS-OCT, except mRNFL at the superonasal area. The inferotemporal GCL++ had the largest AUROC value (0.904), followed by inferotemporal GCL+ (0.882), inferotemporal GCIPL thickness (0.871), inferior GCL++ (0.866), inferior cpRNFL thickness by SS-OCT (0.846), inferior cpRNFL thickness by SD-OCT (0.841), and inferotemporal mRNFL thickness (0.840). The diagnostic performance was comparable between inferotemporal mRNFL thickness and the best measures of GCL (inferotemporal GCL++, p = 0.098) and cpRNFL (inferior cpRNFL thickness by SS-OCT, p = 0.546). CONCLUSION: The diagnostic ability of mRNFL thickness was comparable to that of the best measures of cpRNFL and GCL analysis for eyes with PPG. Therefore, mRNFL thickness could be a new parameter to detect early structural changes in PPG.

Dynamic Near-Infrared Circularly Polarized Luminescence Encoded by Transient Supramolecular Chiral Assemblies.

Circularly polarized luminescence (CPL) is promising for applications in many fields. However, most systems involving CPL are within the visible range; near-infrared (NIR) CPL-active materials, especially those that exhibit high glum values and can be controlled spatially and temporally, are rare. Herein, dynamic NIR-CPL with a glum value of 2.5×10-2 was achieved through supramolecular coassembly and energy-transfer strategies. The chiral assemblies formed by the coassembly between adenosine triphosphate (ATP) and a pyrene derivative exhibited a red CPL signal (glum of 10-3). The further introduction of sulfo-cyanine5 resulted in a energy-transfer process, which not only led to the NIR CPL but also increased the glum value to 10-2. Temporal control of these chiral assemblies was realized by introducing alkaline phosphatase to fabricate a biomimetic enzyme-catalyzed network, allowing the dynamic NIR CPL signal to be turned on. Based on these enzyme-regulated temporally controllable dynamic CPL-active chiral assemblies, a multilevel information encryption system was further developed. This study provides a pioneering example for the construction of dynamic NIR CPL materials with the ability to perform temporal control via the supramolecular assembly strategy, which is expected to aid in the design of supramolecular complex systems that more closely resemble natural biological systems.

Downregulation of MYBL1 in endothelial cells contributes to atherosclerosis by repressing PLEKHM1-inducing autophagy.

MYBL1 is a strong transcriptional activator involved in the cell signaling. However, there is no systematic study on the role of MYBL1 in atherosclerosis. The aim of this study is to elucidate the role and mechanism of MYBL1 in atherosclerosis. GSE28829, GSE43292 and GSE41571 were downloaded from NCBI for differentially expressed analysis. The expression levels of MYBL1 in atherosclerotic plaque tissue and normal vessels were detected by qRT-PCR, Western blot and Immunohistochemistry. Transwell and CCK-8 were used to detect the migration and proliferation of HUVECs after silencing MYBL1. RNA-seq, Western blot, qRT-PCR, Luciferase reporter system, Immunofluorescence, Flow cytometry, ChIP and CO-IP were used to study the role and mechanism of MYBL1 in atherosclerosis. The microarray data of GSE28829, GSE43292, and GSE41571 were analyzed and intersected, and then MYBL1 were verified. MYBL1 was down-regulated in atherosclerotic plaque tissue. After silencing of MYBL1, HUVECs were damaged, and their migration and proliferation abilities were weakened. Overexpression of MYBL1 significantly enhanced the migration and proliferation of HUVECs. MYBL1 knockdown induced abnormal autophagy in HUVEC cells, suggesting that MYBL1 was involved in the regulation of HUVECs through autophagy. Mechanistic studies showed that MYBL1 knockdown inhibited autophagosome and lysosomal fusion in HUVECs by inhibiting PLEKHM1, thereby exacerbating atherosclerosis. Furthermore, MYBL1 was found to repress lipid accumulation in HUVECs after oxLDL treatment. MYBL1 knockdown in HUVECs was involved in atherosclerosis by inhibiting PLEKHM1-induced autophagy, which provided a novel target of therapy for atherosclerosis.

Multimode Stimuli-Responsive Room-Temperature Phosphorescence Achieved by Doping Butterfly-like Fluorogens into Crystalline Small-Molecular Hosts.

Materials with stimuli-responsive purely organic room-temperature phosphorescence (RTP) exempt from exquisite molecular design and complex preparation are highly desirable but still relatively rare. Moreover, most of them work in a single switching mode. Herein, we employ a versatile host-guest-doped strategy to facilely construct efficient RTP systems with multimode stimuli-responsiveness without ingenious molecular design. By conveniently doping butterfly-like guests, namely, N,N'-diphenyl-dihydrodibenzo[a,c]phenazines (DPACs), featured with vibration-induced emission into the small-molecular hosts via various methods, RTP systems with finely tunable photophysical properties are readily obtained. Through systematic mechanistic studies and with the aid of a series of control experiments, we unveil the critical role of the host crystallinity in achieving efficient RTP. By virtue of the inherent environmental sensitivity of both RTP and fluorescence of the DPACs, our systems exhibit multiple-stimuli-responsiveness with the luminescence not only switching between the fluorescence and phosphorescence but also continuously changing in the fluorescence color. Advanced dynamic anticounterfeiting and multilevel information encryption is thereby realized.

Association between alcohol consumption and chronic kidney disease: a population-based survey.

BACKGROUND: Alcohol consumption is associated with both beneficial and harmful effects, and the role of alcohol consumption in chronic kidney disease (CKD) remains inconclusive. This study aimed to investigate the relationship between alcohol consumption and CKD or estimated glomerular filtration rate (eGFR). METHODS: This study enrolled adults from the second Taiwanese Survey on Prevalences of Hypertension, Hyperglycemia, and Hyperlipidemia, conducted in 2007. Participants were categorized into frequent drinkers, occasional drinkers, and nondrinkers. The amount of alcohol consumption was assessed by standard drinks per week. The primary outcome was the presence of CKD, and the secondary outcome was the eGFR. RESULTS: Among 3967 participants with a mean age of 47.9 years and a CKD prevalence of 11.7%, 13.8% were frequent drinkers, and 23.1% were occasional drinkers. The average amount of alcohol consumed was 3.3 drinks per week. Frequent drinkers (odds ratio [OR] 0.622, 95% confidence interval [CI] 0.443-0.874) and occasional drinkers (OR 0.597 95% CI 0.434-0.821) showed a lower prevalence of CKD than nondrinkers. Consumption of a larger number of standard drinks was associated with a lower prevalence of CKD (OR 0.872, 95% CI 0.781-0.975). Frequent drinkers and those who consumed a larger number of standard drinks per week showed higher eGFRs. CONCLUSION: Within the range of moderate alcohol intake, those who consumed more alcohol had a higher eGFR and reduced prevalence of CKD. The potentially harmful effects of heavy drinking should be taken into consideration, and alcohol intake should be limited to less than light to moderate levels.

Concurrent vs Staged Hybrid Ablation for Long-Standing Persistent Atrial Fibrillation: A Propensity-Matched Cohort Study.

BACKGROUND: Long-term success rates of catheter ablation (CA) for long-standing persistent atrial fibrillation (LSPAF) are less than satisfactory. Further improvement of ablation methods is crucial for enhancing the treatment of LSPAF. OBJECTIVES: This study sought to compare the outcomes of concurrent vs staged minimally invasive surgical-catheter hybrid ablation for LSPAF. METHODS: From December 2015 to December 2021, 104 matched patients (concurrent and staged, 1:1) were included in study. In the concurrent group, both left unilateral thoracoscopic epicardial ablation (EA) and CA were performed simultaneously in one procedure. In the staged group, EA was performed at the first hospitalization. If the patients experienced atrial fibrillation (AF) recurrence, CA was performed between 3 months and 1 year after EA. RESULTS: In the concurrent group, 4 patients were restored to sinus rhythm after EA, and 41 were patients restored to sinus rhythm during CA; 86.5% (45 of 52) achieved intraprocedural AF termination during concurrent hybrid ablation. In the staged group, all 52 patients underwent staged CA because of the recurrence of AF or atrial tachycardia (AT). Forty-seven (90.4%) patients achieved intraprocedural AF or AT termination during CA. Freedom from AF or AT off antiarrhythmic drugs at 2 years after hybrid ablation was 79.9% ± 5.7% in the concurrent group and 86.0% ± 4.9% in the staged group (P = 0.390). Failure of intraprocedural AF termination (HR: 14.378) was an independent risk factor for AF recurrence after hybrid ablation. CONCLUSIONS: Both concurrent and staged hybrid ablation could be safely and effectively applied to treat LSPAF. Improving the intraprocedural AF termination rate predicted better outcomes.

ARID1A regulates DNA repair through chromatin organization and its deficiency triggers DNA damage-mediated anti-tumor immune response.

AT-rich interaction domain protein 1A (ARID1A), a SWI/SNF chromatin remodeling complex subunit, is frequently mutated across various cancer entities. Loss of ARID1A leads to DNA repair defects. Here, we show that ARID1A plays epigenetic roles to promote both DNA double-strand breaks (DSBs) repair pathways, non-homologous end-joining (NHEJ) and homologous recombination (HR). ARID1A is accumulated at DSBs after DNA damage and regulates chromatin loops formation by recruiting RAD21 and CTCF to DSBs. Simultaneously, ARID1A facilitates transcription silencing at DSBs in transcriptionally active chromatin by recruiting HDAC1 and RSF1 to control the distribution of activating histone marks, chromatin accessibility, and eviction of RNAPII. ARID1A depletion resulted in enhanced accumulation of micronuclei, activation of cGAS-STING pathway, and an increased expression of immunomodulatory cytokines upon ionizing radiation. Furthermore, low ARID1A expression in cancer patients receiving radiotherapy was associated with higher infiltration of several immune cells. The high mutation rate of ARID1A in various cancer types highlights its clinical relevance as a promising biomarker that correlates with the level of immune regulatory cytokines and estimates the levels of tumor-infiltrating immune cells, which can predict the response to the combination of radio- and immunotherapy.

Butyrate attenuates the stemness of lung cancer cells through lysosome Fe2+- and SLC7A11-mediated ferroptosis.

Cancer stem cells (CSCs) are considered key contributors to tumor progression, and ferroptosis has been identified as a potential target for CSCs. We have previously shown that butyrate enhances the ferroptosis induced by erastin in lung cancer cell, this study aimed to investigate the impact of butyrate on the progression of lung CSCs. To investigate these effects, we constructed a series of in vitro experiments, including 3D non-adherent sphere-formation, cytometry analysis, assessment of CSC marker expression, cell migration assay, and in vivo tumorigenesis analyses. Additionally, the influence of butyrate on chemotherapeutic sensitivity were determined through both in vitro and in vivo experiments. Mechanistically, immunofluorescence analysis was employed to examine the localization of biotin-conjugated butyrate. We identified that butyrate predominantly localized in the lysosome and concurrently recruited Fe2+ in lysosome. Moreover, butyrate reduced the stability of SLC7A11 protein stability in lung cancer cells through ubiquitination and proteasome degradation. Importantly, the effects of butyrate on lung CSCs were found to be dependent on lysosome Fe2+- and SLC7A11-mediated ferroptosis. In summary, our results demonstrate that butyrate could induce the ferroptosis in lung CSCs by recruiting Fe2+ in lysosome and promoting the ubiquitination-lysosome degradation of SLC7A11 protein.

Effectiveness of Maze IV procedure versus thoracoscopic ablation for atrial fibrillation: a propensity score-matched analysis.

Background: Thoracoscopic ablation (TA) has emerged as a promising treatment for atrial fibrillation (AF), with the Cox-Maze IV Procedure (CMP-IV) as the current gold-standard intervention. This study aims to evaluate and compare the outcomes of TA and CMP-IV in treating AF. Methods: Patients with AF underwent either CMP-IV or TA through a left-side chest approach. The CMP-IV entailed bi-atrium ablation, whereas the TA involved creating three circular plus three linear ablations in the left atrium. We analyzed baseline characteristics, perioperative outcomes and recurrence rates using propensity score matching (PSM) at a 1:1 ratio, to ensure comparability between the two treatment groups. Results: A total of 459 patients underwent either CMP-IV (n=93) or TA via left chest (n=366) and 174 patients were deemed eligible for 1:1 PSM. The TA group experienced significantly shorter intensive care unit (ICU) and hospital stays. The mean follow-up period was 31.5±22.1 months. Pre- and post-matching analysis showed that CMP-IV had a higher rate of freedom from recurrence compared to TA, particularly in non-paroxysmal AF patients. Multivariable Cox regression analysis revealed that CMP-IV was associated with a reduced risk of recurrence, while an increased left atrial size emerged as an independent predictor of postoperative recurrence, regardless of the use of CMP-IV or TA. Conclusions: Our study suggests that while the therapeutic efficacy of TA for "lone" AF may fall short of the classic CMP-IV, its less invasive nature results in significantly shorter ICU and hospital stays. To enhance patient outcomes following TA, it is essential to improve the quality of ablation, refine the ablation route, and focus on careful patient selection.

Tailoring raloxifene into single-component molecular crystals possessing multilevel stimuli-responsive room-temperature phosphorescence.

Simultaneously achieving room-temperature phosphorescence (RTP) and multiple-stimuli responsiveness in a single-component system is of significance but remains challenging. Crystallization has been recognized to be a workable strategy to fulfill the above task. However, how the molecular packing mode affects the intersystem crossing and RTP lifetime concurrently remains unclear so far. Herein, four economic small-molecular compounds, analogues of the famous drug raloxifene (RALO), are facilely synthesized and further explored as neat single-component and stimuli-responsive RTP emitters via crystallization engineering. Thanks to their simple structures and high ease to crystallize, these raloxifene analogues function as models to clarify the important role of molecular packing in the RTP and stimuli-responsiveness properties. Thorough combination of the single-crystal structure analysis and theoretical calculations clearly manifests that the tight antiparallel molecular packing mode is the key point to their RTP behaviors. Interestingly, harnessing the controllable and reversible phase transitions of the two polymorphs of RALO-OAc driven by mechanical force, solvent vapor, and heat, a single-component multilevel stimuli-responsive platform with tunable emission color is established and further exploited for optical information encryption. This work would shed light on the rational design of multi-stimuli responsive RTP systems based on single-component organics.

Promoting the Near-Infrared-II Fluorescence of Diketopyrrolopyrrole-Based Dye for In Vivo Imaging via Donor Engineering.

Small-molecule dyes for fluorescence imaging in the second near-infrared region (NIR-II, 900-1880 nm) hold great promise in clinical applications. Constructing donor-acceptor-donor (D-A-D) architectures has been recognized to be a feasible strategy to achieve NIR-II fluorescence. However, the development of NIR-II dyes via such a scheme is hampered by the lack of high-performance electron acceptors and donors. Diketopyrrolopyrrole (DPP), as a classic organic optoelectronic material, enjoys strong light absorption, high fluorescence quantum yield (QY), and facile derivatization. Nevertheless, its application in the NIR-II imaging field has been hindered by its limited electron-withdrawing ability and the aggregation-caused quenching (ACQ) effect resulting from the planar structure of DPP. Herein, with DPP as an electron acceptor and through donor engineering, we have successfully designed and synthesized a DPP-based dye named T-27, in which the strong D-A interaction confers excellent NIR absorption and high-brightness NIR-II fluorescence tail emission. By strategically introducing long alkyl chains on the donor unit to increase intermolecular spacing and reduce the influence of solvent molecules, T-27 exhibits an improved anti-ACQ effect in aqueous solutions. After being encapsulated into DSPE-PEG2000, T-27 nanoparticles (NPs) show a relative NIR-II fluorescence QY of 3.4% in water, representing the highest value among the DPP-based NIR-II dyes reported to date. The outstanding photophysical properties of T-27 NPs enable multimode NIR-IIa bioimaging under 808 nm excitation. As such, the T-27 NPs can distinguish mouse femoral vein and artery and achieve cerebral vascular microscopic imaging with a penetrating depth of 800 µm, demonstrating the capability for high-resolution deep-tissue imaging. This work holds significant potential in the field of bioimaging and provides a new strategy for developing bright NIR-II dyes.

Butyrate enhances erastin-induced ferroptosis of lung cancer cells via modulating the ATF3/SLC7A11 pathway.

Ferroptosis is a novel form of programmed cell death triggered by iron-dependent lipid peroxidation and has been associated with various diseases, including cancer. Erastin, an inhibitor of system Xc-, which plays a critical role in regulating ferroptosis, has been identified as an inducer of ferroptosis in cancer cells. In this study, we investigated the impact of butyrate, a short-chain fatty acid produced by gut microbiota, on erastin-induced ferroptosis in lung cancer cells. Our results demonstrated that butyrate significantly enhanced erastin-induced ferroptosis in lung cancer cells, as evidenced by increased lipid peroxidation and reduced expression of glutathione peroxidase 4 (GPX4). Mechanistically, we found that butyrate modulated the pathway involving activating transcription factor 3 (ATF3) and solute carrier family 7 member 11 (SLC7A11), leading to enhanced erastin-induced ferroptosis. Furthermore, partial reversal of the effect of butyrate on ferroptosis was observed upon knockdown of ATF3 or SLC7A11. Collectively, our findings indicate that butyrate enhances erastin-induced ferroptosis in lung cancer cells by modulating the ATF3/SLC7A11 pathway, suggesting its potential as a therapeutic agent for cancer treatment.

A Novel System for Transcatheter Aortic Valve Implantation: First-in-Man Study.

Transcatheter aortic valve implantation (TAVI) has become a therapeutic treatment for severe symptomatic patients with aortic stenosis. This study aimed to test a novel transcatheter aortic self-expandable bioprosthesis-the ScienCrown system (Lepu Medtech Inc., Beijing, China)-and evaluate the safety of the new device during TAVI. ScienCrown aortic valve implantation was performed on 10 patients. Clinical assessment was performed at baseline, post procedure, and after 1 year. Clinical outcomes and adverse events were assessed according to Valvular Academic Research Consortium-3 criteria. The mean age was 75.30 ± 4.78 years with a mean Society of Thoracic Surgeons score of 4.64 ± 3.23%. Device success was achieved in all patients (80% transfemoral, 20% transapical). After 1 year, there were no deaths, disabling strokes, myocardial infarctions, conversions to surgery, or major procedure-related complications. New pacemaker implantation was required in one patient (10%). ScienCrown implantation resulted in a reduction in mean valve gradient (63.00 ± 18.84 to 9.67 ± 4.97 mm Hg, p <0.001) and an increase in effective orifice area (0.57 ± 0.20 to 2.57 ± 0.59 cm2, p <0.001) at 1 year. Paravalvular leak was absent in 9 patients (90%), and there was a trace in one patient (10%). All patients were in New York Heart Association class I to II at a mean follow-up of 1 year. The experience showed that ScienCrown transcatheter aortic valve system was safely and successfully implanted for treatment of severe symptomatic aortic stenosis. The newer-generation device affords a stable implantation while providing optimal hemodynamic performance.