Mitochondria and their biomacromolecular complexes-such as the electron transport chain (ETC), mitochondrial permeability transition pore (mPTP), and protein quality control systems-play pivotal roles in aging and age-related diseases. This review integrates recent insights into how structural and functional disruptions of these complexes drive cellular senescence and systemic decline. We outline the architecture of mitochondrial assemblies (e.g., oxidative phosphorylation (OXPHOS) complexes, mtDNA-protein interactions) essential for energy production and organelle stability. Age-related alterations in stoichiometry, conformational states (e.g., mPTP opening), and post-translational modifications (e.g., SIRT3-mediated acetylation) compromise mitochondrial integrity, fueling metabolic dysfunction and chronic inflammation ("inflammaging"). Therapeutic strategies include small-molecule stabilizers of ETC supercomplexes, peptide-based mPTP inhibitors, and CRISPR-mediated correction of mtDNA-protein mismatches. Tissue-specific models (e.g., Complex I in skin aging, Bcl-2 protein imbalance in ovarian aging) exemplify the clinical relevance. We also categorize nine age-associated diseases-neurodegenerative, cardiovascular, and cancer types-based on their dependence on distinct mitochondrial complexes, such as ATP synthase in cancer resistance and the TIM/TOM import machinery in Alzheimer's disease. By linking structural findings (e.g., cryo-EM studies) with therapeutic innovation, this review offers a framework for targeting mitochondrial complexes to mitigate aging and its related pathologies.

Individual cardiometabolic diseases are associated with psychiatric conditions and suicide. However, the association between the recently proposed Cardiovascular-Kidney-Metabolic (CKM) syndrome framework and suicide-related mortality remains unevaluated.

We analyzed data from 4,601,001 participants in the Korean National Health Insurance Service database, categorizing CKM health into Stages 0-4. The association between CKM stages and suicide-related mortality was evaluated using multivariable Cox regression with sequential adjustment for clinicodemographic variables, comorbidity, and claims-based psychiatric diagnoses, and using Fine-Gray subdistribution hazard models treating non-suicide death as a competing event.

During a median follow-up of 10.11 years, 12,034 suicidal death events occurred. After adjustment, advanced CKM stages were associated with an increased risk of suicidal death (stage 3: adjusted HR 1.328, 95% CI 1.217-1.449; stage 4: adjusted HR 1.319, 95% CI 1.220-1.426), and the association persisted after further adjustment for other psychiatric disorders. Estimates were attenuated but remained significant in Fine-Gray models accounting for the competing risk of non-suicide death (stage 3: subdistribution HR 1.199, 95% CI 1.098-1.310; stage 4: 1.246, 95% CI 1.150-1.349). Exploratory subgroup analyses indicated that the association was most pronounced in younger adults aged 20-39 and in individuals without a claims-based diagnosis of depression.

Advanced CKM syndrome is associated with increased suicide-related mortality. Mental health surveillance within the clinical management of CKM dysfunction may serve as a potential preventive strategy. Future studies are needed to evaluate the utility of CKM-based risk stratification in suicidal death prevention.

In patients with nonischemic cardiomyopathy (NICM) undergoing cardiac resynchronization therapy (CRT), there are no clear recommendations on selecting CRT with defibrillator (CRT-D) vs pacemaker (CRT-P). Patients with high probability of response to CRT and low arrhythmic risk may be ideal candidates to CRT-P.

The objectives of the study was to evaluate if the absence of late gadolinium enhancement (LGE) is associated with CRT response and ventricular arrhythmia (VA) in NICM treated with CRT.

A systematic review and meta-analysis was conducted. Search of PubMed, Web of Science, and Scopus identified observational studies of NICM patients who underwent cardiac magnetic resonance before CRT implantation. Studies assessing echocardiographic response to CRT or VA stratified by LGE status were included. The VA endpoint comprised sustained ventricular tachycardia, appropriate implantable cardioverter-defibrillator therapy, resuscitated cardiac arrest, and sudden death.

Ten studies were included: 9 (n = 831) for CRT response and 6 (745 patients) for arrhythmic risk. CRT response was significantly higher in patients without LGE than in patients with LGE (78.7% vs 50.7%; P < 0.001). The cumulative incidence of VA was extremely low in LGE cases, significantly lower than that of LGE+ ones (0.8% vs 21.1%, P < 0.001). The absence of LGE was strongly associated with higher CRT response (OR: 3.52; 95% CI: 2.54-4.88; P < 0.001) and much lower arrhythmic risk (OR: 0.06; 95% CI: 0.02-0.15; P < 0.001).

In NICM patients undergoing CRT, the absence of LGE is strongly associated with greater echocardiographic response and very low arrhythmic risk. In this subgroup the incremental benefit of CRT with defibrillator over CRT-P may be limited.

Obstructive sleep apnea (OSA) is closely linked with cardiovascular disease (CVD), but different cardiovascular phenotypes may influence ECG-derived RR interval dynamics differently. Previous work has shown that scale-dependent detrended fluctuation analysis (sDFA) can detect OSA across broad CVD status, but it remains unclear whether this relationship differs between CVD subtypes.

Overnight polysomnography recordings from the Sleep Heart Health Study were analyzed in participants with a history of myocardial infarction (MI), congestive heart failure (CHF), or angina pectoris (ANG). Participants with more than one of these conditions were excluded. OSA was analyzed as a binary outcome using an apnea-hypopnea index threshold of 5 events/h. Propensity score matching was performed within each subgroup using age and body mass index. ECG-derived RR interval dynamics were analyzed using cHRV metrics and second-order sDFA, with discrimination assessed using ROC-AUC.

The matched subgroups consisted of 112 participants with MI, 18 with CHF, and 54 with ANG. sDFA achieved higher ROC-AUC values than cHRV metrics in all subgroups. The highest sDFA ROC-AUC was observed in ANG (0.79), compared with 0.66 in MI and 0.69 in CHF. MI and ANG showed broadly similar scale-dependent profiles, whereas CHF appeared distinct; however, the CHF analysis was substantially underpowered.

ECG-derived sDFA features showed subtype-dependent behavior for OSA discrimination, with the strongest performance observed in ANG. These exploratory findings suggest that cardiovascular phenotype may influence OSA-related RR interval dynamics. Binary OSA grouping may mask severity-related differences, while exclusion of participants with multiple cardiovascular conditions limits clinical applicability.

Spontaneous intracranial hypotension (SIH) is most commonly caused by spinal CSF leaks, with ventral dural defects frequently requiring surgical repair when conservative measures fail. Endoscopic transforaminal approaches have emerged as minimally invasive alternatives to traditional open techniques, but the physiological consequences of continuous irrigation in the presence of a dural defect remain poorly understood. The authors report the case of a 36-year-old woman with recurrent SIH due to a persistent ventral T11-12 CSF leak despite prior laminectomy, revision repair, and multiple targeted interventions. She underwent transforaminal endoscopic discectomy and ventral dural repair. During the procedure, under continuous gravity-assisted irrigation, she developed sudden, severe, and reproducible hypertension with her systolic blood pressure reaching 275 mm Hg, refractory to anesthetic deepening and multiple antihypertensive agents. Irrigation cessation resulted in immediate hemodynamic normalization, while irrigation reintroduction led to recurrence of the hypertensive response. The procedure was completed after minimizing irrigation, and the patient stabilized postoperatively without further hemodynamic instability. The authors propose that this phenomenon reflects direct transmission of irrigation-induced epidural pressure into the intrathecal space through the persistent dural defect, resulting in acute intracranial pressure elevation and sympathetic activation. In contrast to standard endoscopic cases, chronic CSF leak states may create a compartmentalized and fibrotic epidural environment with reduced compliance and impaired outflow, predisposing the epidural space/operative field to rapid pressure accumulation even under low-pressure irrigation systems. This case highlights a previously underrecognized mechanism of intraoperative hemodynamic instability during endoscopic spine surgery and underscores the importance of considering altered pressure dynamics in patients with CSF leaks. Surgeons should maintain a high index of suspicion for irrigation-related complications in this population and consider strategies to minimize inflow pressure, optimize outflow, and promptly interrupt irrigation in the setting of unexplained physiological changes. These findings have important implications for surgical planning, intraoperative management, and the safe expansion of endoscopic techniques in CSF leak repair.

Hypertension worsens osteoarthritis and could be a therapeutic target in patients with both conditions.

To evaluate associations of cardiovascular health (CVH) based on Life's Essential 10 (LE10) with all-cause mortality, cardiovascular disease (CVD) and cancer mortality and incidence, and life expectancy free of CVD and cancer.

This prospective study included 110,806 UK Biobank participants (aged 37-73) and 20,031 National Health and Nutrition Examination Survey (NHANES) participants (aged ≥20). LE10 (0-100), which integrates alcohol consumption and mental health with Life's Essential 8, categorised CVH as low (<60), moderate (60-79), and high (≥80). Cox regression and competing risk models were applied to estimate adjusted hazard ratios (aHRs). Life expectancy was calculated using multi-state and flexible parametric survival models. Over a median follow-up of 13.8 years, 6137 deaths, 13,968 CVD events, and 18,077 cancer cases were documented in UK Biobank. In UK Biobank, high CVH was associated with lower risks of all-cause mortality (men: aHR 0.43, 95% CI 0.39-0.48; women: aHR 0.34, 95% CI 0.29-0.39), alongside CVD and cancer mortality and incidence, compared to low CVH. At age 50, high CVH conferred greater projected overall (men +5.47 years, women +5.85) and disease-free life expectancy (men +4.02 years, women +4.40). Having more low-risk CVH metrics was associated with up to 9.73 years of projected gains in life expectancy. Associations were replicated and consistent in 7.2-year NHANES follow-up.

Higher LE10-based CVH levels were associated with lower all-cause mortality, reduced CVD and cancer mortality and incidence, and longer life expectancy free of CVD and cancer. LE10 may provide additional targets for CVH management.

BACKGROUND Evaluation of multidrug-resistant hypertension in young adults requires consideration of uncommon secondary etiologies, including renovascular disease and congenital renal vascular anomalies. Renal arteriovenous malformations (rAVMs) represent a rare cause of secondary hypertension, accounting for less than 0.1% of renal vascular abnormalities. They most commonly present with hematuria, flank pain, or, in high-flow lesions, high output cardiac failure. Hypertension as the principal manifestation is uncommon. CASE REPORT We describe a 33-year-old woman with longstanding uncontrolled hypertension requiring 5 antihypertensive agents who presented for evaluation of refractory blood pressure control. Initial duplex ultrasound and angiography identified a large complex left renal lesion associated with dysmorphic parenchyma and aberrant arterial and venous architecture without a history of trauma, intervention, or prior renal surgery, consistent with a congenital vascular malformation. Diagnostic computed tomography angiography demonstrated a 6.5×6.5×5.5 cm arteriovenous malformation. Given the lesion's size and vascular complexity, endovascular embolization was deemed not technically feasible. The patient subsequently underwent elective simple nephrectomy without intraoperative complication. Histopathology confirmed a congenital high-flow rAVM with extensive parenchymal distortion. Postoperatively, the patient exhibited marked improvement in blood pressure control, eliminating the need for antihypertensive medication. CONCLUSIONS This case illustrates an uncommon presentation of severe drug-resistant hypertension in a young patient likely attributed to a large congenital rAVM. Congenital renal vascular malformations should be considered in the differential diagnosis of refractory hypertension. Surgical intervention remains an important therapeutic option when endovascular treatment is contraindicated or considered unlikely to preserve functional renal parenchyma.

This study examined the association of weekly plant-based medically tailored groceries (MTGs) with cardiovascular-kidney-metabolic outcomes among patients with food insecurity. The intervention began on December 20, 2019, and ended on April 1, 2025 (275 weeks). Linear mixed-effects models estimated the dose-dependent association of MTGs received and the rates of changes in blood pressure, glycated hemoglobin A_1c, weight, and body mass index from baseline to follow-up periods. Among 68 adults, during an average of 2.7 years, each 100 MTGs received was associated with a greater improvement from baseline to follow-up periods in the rates of changes in diastolic blood pressure (-3.21 mm Hg; 95% CI, -4.89 to -1.52), weight (-2.63 kg; 95% CI, -3.73 to -1.53), and body mass index (-1.04 kg/m²; 95% CI, -1.50 to -0.58).

α-Lipoic acid (LA) is a naturally occurring small molecule possessing both endogenous cofactor activity and dynamic covalent polymerization capability. The 1,2-dithiolane ring in its structure enables both redox-responsive biological functions and ring-opening polymerization to yield polylipoic acid (PolyLA) with a dynamic disulfide backbone, bridging small-molecule medicinal chemistry and functional polymeric materials within a single molecular platform. This Review systematically outlines the full landscape of LA research, covering its chemical foundations, biological functions, polymer chemistry, and biomedical applications. We elaborate on the multi-pathway redox and anti-inflammatory network of LA and its reduced form, as well as their vital roles as mitochondrial cofactors in energy metabolism and insulin sensitivity. We then compare the mechanisms and applicable scenarios of various ring-opening strategies, dissect the origin of room-temperature PolyLA depolymerization, and summarize the corresponding stabilization strategies. Further, we propose a three-stage evolutionary framework for LA-based nanoscale delivery systems, ranging from physical encapsulation and chemical conjugation to the therapeutic self-carrier paradigm; we also systematically recapitulate their design rationales and mechanisms in treating tumors, nerve injury, diabetic complications, inflammatory diseases, and cardiovascular diseases. As for dynamic biomaterials, PolyLA-based adhesives and flexible sensors leverage dynamic disulfide bonds and carboxyl groups to achieve universal adhesion, tissue integration, self-healing, and recyclable properties. Finally, we identify the core bottlenecks hindering clinical translation and outline forward-looking outlooks for this field. By establishing an integrated framework that connects molecular structure to multifunctional applications of LA-based biomaterials, this Review highlights how interdisciplinary integration unlocks innovative research avenues and accelerates the clinical translation of LA-derived therapeutics and biomaterials.