Mitochondria and NLRP3: To die or inflame.

Mitochondria play critical roles in intrinsic apoptosis and NLRP3 inflammasome activation, but how these processes are interconnected remains unclear. In this issue of Immunity, Saller et al. unveiled the complexity of NLRP3 activators, highlighting mitochondria's roles in switching apoptosis to NLRP3 inflammasome activation.

Early Identification of Myocardial Microstructural Alterations in Hypertrophic Cardiomyopathy with in Vivo Cardiac Diffusion-Tensor Imaging.

Purpose To explore the diffusion characteristics of hypertrophic cardiomyopathy (HCM) using in vivo cardiac diffusion-tensor imaging (cDTI) and to determine whether cDTI could help identify abnormal myocardium beyond cardiac MRI findings of fibrosis and hypertrophy. Materials and Methods In this prospective study conducted from April to August 2023, participants with HCM and healthy volunteers were enrolled for cardiac MRI evaluation, including cine, late gadolinium enhancement (LGE), T1 mapping, and cDT imaging, using a 3.0-T scanner.

Tenecteplase Thrombolysis for Stroke up to 24 Hours After Onset With Perfusion Imaging Selection: The CHABLIS-T II Randomized Clinical Trial.

Background: Whether it is effective and safe to extend the time window of intravenous thrombolysis up to 24 hours after the last known well is unknown. We aimed to determine the efficacy and safety of tenecteplase in Chinese patients with acute ischemic stroke due to large/medium vessel occlusion within an extended time window.

Methods: Patients with ischemic stroke presenting 4.

Pulsed Field Ablation of Paroxysmal Supraventricular Tachycardia: A Prospective Multicenter Single-Arm Study in China.

Background: Pulsed field ablation (PFA) has gained attention in cardiac electrophysiology, but data on its application to paroxysmal supraventricular tachycardia are limited. This study aimed to assess the feasibility and safety of PFA and its combination with radiofrequency ablation for treating paroxysmal supraventricular tachycardia.

Methods: A prospective, multicenter, single-arm study was conducted across 8 centers in China.

Effects of Extracted Pulse Proteins on Lipid Targets for Cardiovascular Risk Reduction: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Many clinical practice guidelines recommend dietary pulses for the prevention and management of cardiovascular disease and diabetes. The impact of extracted pulse proteins remains unclear. We therefore conducted a systematic review and meta-analysis of randomized controlled trials of the effect of extracted pulse proteins on therapeutic lipid targets.

Extensive Biotransformation Profiling of AZD8205, an Anti-B7-H4 Antibody-Drug Conjugate, Elucidates Pathways Underlying Its Stability .

What happens to macromolecules ? What drives the structure-activity relationship and stability for antibody-drug conjugates (ADCs)? These interrelated questions are increasingly relevant due to the re-emerging importance of ADCs as an impactful therapeutic modality and the gaps that exist in our understanding of ADC structural determinants that underlie ADC stability. Complex macromolecules, such as ADCs, may undergo changes due to their intricate structure as biotransformations may occur on the linker, the payload, and/or at the modified conjugation site. Furthermore, the dissection of ADC metabolism presents a substantial analytical challenge due to the difficulty in the identification or quantification of minor changes on a large macromolecule.

N-doped Porous Carbon Derived from the Pyrolysis of a Polydopamine-coated Hypercross-linked Polymer for Enhanced CO Adsorption.

Porous carbon materials can simultaneously capture and convert carbon dioxide, helping to reduce greenhouse gas emissions and using carbon dioxide as a feedstock for the production of valuable chemicals or fuel. In this work, a series of N-doped porous carbons (PDA@HCP(x:y)-T) was prepared; the CO adsorption capacity of the prepared PDA@HCP(x:y)-T was enhanced by coating polydopamine (PDA) on a hypercross-linked polymer (HCP) and then adjusting the mass ratio of PDA to HCP and the carbonization temperature. The results showed that the prepared PDA@HCP(1 : 1)-850 exhibited a high CO adsorption capacity due to abundant micropores (0.

Development of an orally bioavailable CDK12/13 degrader and induction of synthetic lethality with AKT pathway inhibition.

Cyclin-dependent kinases 12/13 play pivotal roles in orchestrating transcription elongation, DNA damage response, and maintenance of genomic stability. Biallelic CDK12 loss has been documented in various malignancies. Here, we develop a selective CDK12/13 PROTAC degrader, YJ9069, which effectively inhibits proliferation in subsets of prostate cancer cells preferentially over benign immortalized cells.

Colocalization of Cancer-Associated Biomarkers on Single Extracellular Vesicles for Early Detection of Cancer.

Detection of cancer early, when it is most treatable, remains a significant challenge because of the lack of diagnostic methods sufficiently sensitive to detect nascent tumors. Early-stage tumors are small relative to their tissue of origin, heterogeneous, and infrequently manifest in clinical symptoms. The detection of early-stage tumors is challenging given the lack of tumor-specific indicators (ie, protein biomarkers, circulating tumor DNA) to enable detection using a noninvasive diagnostic assay.

Improving Executive Function and Dual-Task Cost in Parkinson Disease: A Randomized Controlled Trial.

Background And Purpose: Dual-task walking is challenging for people with Parkinson disease (PD). Gait performance worsens while executing dual tasks, possibly due to a decline in executive function (EF). This study aimed to investigate the effects of dual-task training on EF and dual-task cost (DTC) in people with PD and to explore whether training-induced changes in EF were associated with changes in DTC.

Endovascular Management of Basilar Artery Aneurysms: A Consecutive Series of 124 Patients.

Background: Currently, there is no established criterion for determining when interventional treatment is necessary or which strategy is appropriate for basilar artery (BA) aneurysms. Through this study, we aimed to propose an algorithm that can effectively determine the optimal endovascular treatment (EVT) option for BA aneurysms.

Methods: We enrolled patients with BA aneurysms from June 2016 to December 2022 and performed procedures based on the algorithm.

Capturing relationships between suturing sub-skills to improve automatic suturing assessment.

Suturing skill scores have demonstrated strong predictive capabilities for patient functional recovery. The suturing can be broken down into several substep components, including needle repositioning, needle entry angle, etc. Artificial intelligence (AI) systems have been explored to automate suturing skill scoring.

Arthroscopic Transtibial Pullout Repair and Tibial Condylar Valgus Osteotomy for Medial Meniscus Posterior Root Tear With Varus Knee.

As an important structure for maintaining the hoop tension of the medial meniscus of the knee joint, the posterior root is receiving increasing attention. Medial meniscus posterior root tear is an important reason for the occurrence, development, and kinematics changes of knee osteoarthritis. It is necessary to repair the posterior root of meniscus for restoring joint kinematics and improving clinical efficacy.

Cholesterol reduction by immunization with a PCSK9 mimic.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a plasma protein that controls cholesterol homeostasis. Here, we design a human PCSK9 mimic, named HIT01, with no consecutive 9-residue stretch in common with any human protein as a potential heart attack vaccine. Murine immunizations with HIT01 reduce low-density lipoprotein (LDL) and cholesterol levels by 40% and 30%, respectively.

Convolutional Neural Network-Based Prediction of Axial Length Using Color Fundus Photography.

Purpose: To develop convolutional neural network (CNN)-based models for predicting the axial length (AL) using color fundus photography (CFP) and explore associated clinical and structural characteristics.

Methods: This study enrolled 1105 fundus images from 467 participants with ALs ranging from 19.91 to 32.

Adjuvant treatment strategy evolution and risk stratification for hormone receptor-positive, human epidermal growth factor receptor-2 negative early breast cancer in China.

Background: Patients with hormone receptor-positive (HR+), human epidermal growth factor receptor-2 negative (HER2-) early breast cancer (EBC) with high-risk clinicopathological features face an increased risk of recurrence. This study explored the evolving treatment landscape and clinical outcomes in patients with EBC using a nationwide database.

Patients And Methods: The study cohort comprised HR+/HER2-, stages 1-3, patients with EBC who underwent surgery and received adjuvant endocrine therapy (AET) from January 2013 to March 2021.

Intensive Ambulance-Delivered Blood-Pressure Reduction in Hyperacute Stroke.

Background: Treatment of acute stroke, before a distinction can be made between ischemic and hemorrhagic types, is challenging. Whether very early blood-pressure control in the ambulance improves outcomes among patients with undifferentiated acute stroke is uncertain.

Methods: We randomly assigned patients with suspected acute stroke that caused a motor deficit and with elevated systolic blood pressure (≥150 mm Hg), who were assessed in the ambulance within 2 hours after the onset of symptoms, to receive immediate treatment to lower the systolic blood pressure (target range, 130 to 140 mm Hg) (intervention group) or usual blood-pressure management (usual-care group).

Artificial Intelligence-Assisted Prescription Determination for Orthokeratology Lens Fitting: From Algorithm to Clinical Practice.

Objectives: To explore the potential of artificial intelligence (AI) to assist prescription determination for orthokeratology (OK) lenses.

Methods: Artificial intelligence algorithm development followed by a real-world trial. A total of 11,502 OK lenses fitting records collected from seven clinical environments covering major brands.

Regeneration of Nonhuman Primate Hearts With Human Induced Pluripotent Stem Cell-Derived Cardiac Spheroids.

Background: The clinical application of human induced pluripotent stem cell-derived cardiomyocytes (CMs) for cardiac repair commenced with the epicardial delivery of engineered cardiac tissue; however, the feasibility of the direct delivery of human induced pluripotent stem cell-derived CMs into the cardiac muscle layer, which has reportedly induced electrical integration, is unclear because of concerns about poor engraftment of CMs and posttransplant arrhythmias. Thus, in this study, we prepared purified human induced pluripotent stem cell-derived cardiac spheroids (hiPSC-CSs) and investigated whether their direct injection could regenerate infarcted nonhuman primate hearts.

Methods: We performed 2 separate experiments to explore the appropriate number of human induced pluripotent stem cell-derived CMs.