Inconsistent links between arterial stiffness and cognition may reflect limited cognitive tests and unaccounted diurnal pulse wave velocity variation. To bridge this knowledge gap, we investigated 24-hour ambulatory estimated pulse wave velocity (ePWV) and its association with dementia-related neuroimaging and cognitive function in hypertension. We assessed 893 patients with hypertension aged ≥50 years (mean age, 67.2 years; 52.3% women), including brain magnetic resonance imaging (n=545), global cognitive testing (n=623), and ambulatory ePWV measurements. White matter hyperintensity and hippocampus were quantified via Computational Anatomy Toolbox 12 and Statistical Parametric Maps 12. Cognition was assessed via the Mini-Mental State Examination and Montreal Cognitive Assessment. Among 623 tested participants, the prevalence of mild cognitive impairment was 10% (Mini-Mental State Examination, n=62) and 18.5% (Montreal Cognitive Assessment, n=115). Cognitive scores decline with higher white matter hyperintensity burden and lower hippocampal volume (P≤0.024). Higher 24-hour ePWV quartiles showed graded associations with higher white matter hyperintensity volume and lower hippocampal volume (both P<0.001) and lower cognitive scores (P≤0.037). Multivariable models showed each 1-SD (+1.2 m/s) increment in 24-hour ePWV were associated with 2.00±1.74 mL greater white matter hyperintensity volume (P=0.004), and 0.54±0.14 mL smaller hippocampal volume (P<0.001), independent of age, systolic blood pressure, and other confounders. These associations persisted after further adjustment for carotid-femoral PWV, which itself showed no independent association (P≥0.18). Results were consistent for daytime and nighttime ePWV and across key subgroups. Ambulatory ePWV is an independent risk factor for dementia-related brain pathology. Targeting arterial stiffness represents a promising strategy for dementia prevention.
Ferroptosis, an iron-dependent form of regulated cell death, holds great promise for eliminating therapy-resistant tumors, but clinical translation has been limited by poor spatiotemporal selectivity and the lack of dynamic control over catalytic activity. Here we present a multi-signal responsive allosteric nanozyme platform that exploits tumor-intrinsic stress amplification (TISA) to achieve spatiotemporally confined ferroptosis. The design integrates three microenvironmental cues-reactive oxygen species (ROS), acidic pH, and elevated glutathione (GSH)-as cooperative allosteric effectors: ROS primes the catalyst, acidic pH accelerates peroxidase-like (POD-like) activity, and intracellular GSH acts as a reversible brake to self-limit activity post-activation. Only upon convergence of all three signals does the nanozyme switch from an off-state to a high-turnover state, triggering localized lipid peroxidation and bypassing systemic oxidative damage. Across orthotopic and metastatic tumor models, TISA nanozymes selectively amplified ferroptotic stress in tumor tissue, overcame antioxidant buffering, and suppressed tumor growth with minimal off-target toxicity. This multi-layered gating and confinement strategy establishes a blueprint for precision ferroptosis nanomedicine and offers a generalizable approach to harness complex tumor microenvironment signals for safe and effective catalytic therapy.
Artificial molecular machines often rely on chemical stimuli to switch between functional states, yet the real-time dynamics of these transitions remain largely obscured by ensemble averaging. We describe the real-time single-molecule tracking of a Diels-Alder reaction that irreversibly alters the co-conformational space of a two-station [2]rotaxane. By tethering individual shuttles in optical tweezers, we observe the transformation of a fumaramide binding site into a non-binding adduct in an aqueous environment. This covalent modification triggers a brisk shift in the macrocycle's positional preference, effectively erasing the thermodynamically favored state and leaving the secondary succinic amide-ester station as the sole anchoring site. Our analysis allows us to reconstruct the energy landscape before and after the chemical event, revealing that the transformation reshapes the thermodynamic potential without measurably perturbing the intrinsic kinetics. This study highlights the potential of force spectroscopy for the in-situ characterization of chemically driven changes in the function of individual molecular devices.
Hydrogen peroxide (H2O2) is an essential chemical and potent energy carrier. Its production through solar energy and metal-free photocatalysts is desirable. Organic semiconductors, as a new generation of semiconductors, can form suitable transition state intermediates showing great ability in enhancing the efficiency and selectivity of photocatalytic H2O2 generation, offering a metal-free, green, and more economical solution. However, the smaller Frenkel exciton radius and larger exciton Coulomb binding energy lead to a constrained capacity for exciton dissociation, blocking the way of photocatalysts based on organic semiconductors. Here, we overcome the bottleneck by cocrystal engineering. A kind of cocrystal photocatalysts with X-packing are designed and synthesized, which permit all excited states to be optically allowed due to reduced energy splitting, enhancing the exciton participation in photosynthesis of H2O2 giving much more efficient singlet exciton dissociation and exciton utilization. Indeed, the X-packed cocrystals show photosynthesis of H2O2 from O2 and H2O at a rate of 2.65 mmol h-1 g-1 and a solar-chemical energy conversion efficiency of 0.42%, which can be further improved to 13.3 mmol h-1 g-1 with a hole sacrificial agent. This work seems to open a new door for high solar exciton utilization with organic semiconductors by cocrystal engineering.
Membranes applied in alkaline flow batteries suffer swelling from spontaneous polymer chain motion, which degrades ion selectivity and mechanical strength. Here, we employ a large language model (LLM)-driven screening workflow to efficiently shortlist crosslinkers from a curated knowledge base, guiding the rational design of a hybrid dual network (H-DN) membrane. The workflow identifies N,N,N',N'-tetramethylethylenediamine as the optimal candidate to build a robust, chemically crosslinked polysulfone network interpenetrated within a widely used sulfonated poly(ether ether ketone) (SPEEK) matrix. Mechanistically, the in situ formed quaternary ammonium motifs strongly ion-pair with sulfonic acid groups, effectively suppressing chain motion without blocking ion transport channels. Consequently, the H-DN membrane exhibits a 68% reduction in swelling and an ultra-high wet-state hardness of 216 MPa (a sixfold increase over SPEEK), while retaining high ionic conductivity (10.7 mS cm-1). Enabled by this mechanically robust and highly selective architecture, the alkaline zinc-iron flow battery achieves an energy efficiency of 88.87% at a challenging areal capacity of 240 mAh cm-2 and operates stably for over 820 h without dendrite-induced failure, which surpassed the commercial Nafion212 and SPEEK benchmarks by threefold and sevenfold, respectively. This work establishes a paradigm for LLM-accelerated material discovery in addressing the stability-selectivity dilemma of ion-exchange membranes.
Vascular calcification (VC), a pathological process driven by the osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs), markedly increases cardiovascular mortality. Vericiguat, a soluble guanylate cyclase stimulator, has shown vascular protective properties, but its role in modulating VC remains poorly investigated. VC models were generated using the nephrectomy method or an adenine diet. Calcification in rat VSMCs and aortic rings was induced by high phosphate. VC was evaluated by Alizarin Red staining, calcium quantification, alkaline phosphatase activity, and imaging. Transcriptomic profiling and viral vector approaches were used to investigate the role of MMP-10 (matrix metalloproteinase 10) in vericiguat-regulated VC. Vericiguat treatment significantly reduced aortic calcification and osteogenic markers of VSMCs both in nephrectomy-induced rats and adenine-induced mice. It also inhibited calcium deposition and the phenotypic switch of VSMCs from a contractile to an osteoblastic state in both aortic ring and VSMC cultures. Transcriptomic profiling identified MMP-10 as a key mediator; MMP-10 was upregulated in VC models, and vericiguat reduced its expression. Overexpression of MMP-10 reversed the protective effects of vericiguat, and lentiviral-mediated MMP-10 knockdown confirmed its procalcific role. Mechanistically, vericiguat increased cGMP-PKG (cyclic guanosine monophosphate-protein kinase G) signaling, including phosphorylated vasodilator-stimulated phosphoprotein and phosphorylated c-Jun (transcription factor Jun), ultimately downregulating MMP-10. Vericiguat inhibits VSMC osteogenic differentiation and attenuates VC by modulating the cGMP-PKG-MMP-10 axis. These findings support vericiguat as a potential therapeutic candidate for VC.
Synthetic cells, assembled from defined molecular components, are designed to mimic the features, form, and function of living cells. Light has emerged as a uniquely precise, biorthogonal, and non-invasive stimulus for regulating and energizing these systems, enabling chemical inhomogeneity and an out-of-equilibrium state central to many cellular processes. This review highlights the biological behaviors and functions that light has helped recreate in synthetic cells, including compartmentalization, energy supply and metabolism, protein synthesis, communication, growth, shape change and division, and motility. We survey the breadth of light-responsive components incorporated into synthetic cells, spanning photoswitchable and photocleavable small molecules, photoswitchable proteins, photocatalysts, nanoparticles, and photosynthetic organelles or organisms. Finally, we offer a perspective on key design considerations such as wavelength, reversibility, integration, biocompatibility, multicolor regulation, and biohybrid strategies. Together, these advances chart promising routes toward more dynamic, energy-autonomous, and programmable synthetic cells that will deepen our understanding of cellular functions and enable emerging biotechnological applications.
To assess for longitudinal changes in the prevalence, duration, and self-perceived impact of persistent tinnitus amongst young adults (ages 18-24) in the United States. The adult National Health Interview Surveys (NHIS) for calendar years 2008 and 2023 were investigated for specific tinnitus related symptoms among young adults (ages 18-24). The prevalence of tinnitus in the past 12 months and the overall duration of tinnitus symptoms were determined and compared between the 2 survey years. In 2023, an estimated 2.30 million young adults reported tinnitus in the prior 12 months, risk for which was increased with very loud sound exposure (odds ratio [95% confidence interval], 2.6 [1.7-3.9]). Tinnitus was reported to be a moderate or big problem in 8.7% and 3.1% of respondents, respectively, and only 10.1% saw a medical specialist for their tinnitus. The prevalence of tinnitus increased from 5.8% in 2008 to 7.8% in 2023 (P = .030). From 2008 to 2023 there was also an increase in duration of tinnitus (P < .001). Nationally representative data indicate a concerning increasing prevalence and duration of tinnitus among young adults with a significant self-perceived impact. This increasing prevalence of tinnitus may reflect underlying issues of noise exposure and merits further ongoing surveillance. IV.
Second harmonic generation (SHG) is a widely used nonlinear optical process for frequency conversion and quantum information processing. However, existing approaches to enhance SHG in metasurfaces that are based on quasi-bound state in the continuum (quasi-BIC) resonances are often constrained by the limited second-order nonlinear susceptibilities of materials and the practical challenge of achieving high quality (Q) factors. Here, an alternative strategy is proposed to enhance SHG by increasing the absorptance (A) at the quasi-BIC resonance. Using temporal coupled mode theory (TCMT), an analytical expression is derived to link SHG intensity with both the resonance Q factor and absorptance, showing that strong SHG can be achieved even with finite Q when absorptance is properly optimized. To validate this concept, a 3R phase of molybdenum disulfide (3R-MoS2) metasurface is designed and fabricated by spectrally aligning a reflective resonance with a transmitted quasi-BIC mode, thereby enhancing absorptance at the target wavelength. The metasurface exhibits an SHG conversion efficiency of ∼3 × 10-5 at 9 GW cm-2, corresponding to more than 40-fold enhancement over an unpatterned flake. Despite the reduced damage threshold, the experimental results agree well with the theoretical model and establish a general design framework for absorptance-engineered metasurfaces for SHG.
Expanded screening with the aldosterone-renin ratio has improved detection of primary aldosteronism, the most common surgically curable cause of arterial hypertension. However, identification of surgically curable primary aldosteronism remains constrained by technical limitations of subtyping by adrenal vein sampling (AVS), as bilateral selectivity often fails. Although alternative biomarkers better than cortisol may help reduce this rate, currently, the failure to achieve bilateral selectivity precludes calculation of the lateralization index and, thus, diverts patients toward lifelong medical therapy. Recent advances have established the relative aldosterone secretion index (RASI) as a physiologically grounded strategy to interpret partially successful AVS. By quantifying aldosterone secretion from each adrenal gland relative to peripheral values and incorporating contralateral suppression, RASI-based interpretation can rescue many AVS studies by enabling subtyping under unilateral selectivity with 80% concordance with the lateralization index, when available. Postoperative outcomes following RASI-guided adrenalectomy approximate those achieved after fully selective AVS, with biochemical cure rates of 85% to 90% and blood pressure improvement in 65% to 75%. Studies published over the past 2 to 3 years have clarified factors influencing RASI performance, including cosyntropin stimulation, variations in aldosterone secretion, and the limited utility of cross-sectional imaging alone for subtype classification. Collectively, the available data support the incorporation of RASI into contemporary AVS interpretation algorithms. As primary aldosteronism management enters a postdetection era, subtyping has emerged as the principal bottleneck to definitive cure. RASI provides a pragmatic, evidence-based means to overcome the imperative dependence on bilateral selectivity while preserving diagnostic accuracy, thereby improving access to adrenalectomy and associated cardiovascular benefits.
The separation of sulfur hexafluoride (SF6) from nitrogen (N2) is an essential challenge for semiconductor industrial gas purification due to the size similarity. While microporous adsorbents exhibit highly selective adsorption, their high-capacity results in greater mass transfer resistance, longer separation times, and increased energy consumption during regeneration. Featuring a tunable shell thickness, core-shell structured PSD@HKUST-1s were synthesized via an in -situ growth approach. Benefiting from the outer-layer gas enrichment effect, the SF6/N2 IAST selectivity of optimized PSD@HKUST-1-AcOH boosts to 924, which is significantly higher than that of pristine HKUST-1, with about 25% lower cost. By leveraging a thin microporous shell to retain high SF6/N2 selectivity while utilizing a mesoporous core to accelerate gas diffusion, PSD@HKUST-1s enable shorter separation times and demonstrate robust cyclic stability. This work highlights PSD@HKUST-1s as cost-effective, high-performance candidates for semiconductor-related SF6/N2 separation and demonstrates a promising strategy via core-shell design and mass transfer optimization.
Evidence for the role of oral microbiota in tongue cancers is limited despite early-onset and unexplained etiology. We assessed oral microbiota profiles in saliva among participants with tongue cancers in the oral cavity compared to cancer-free controls. We conducted a case-control study in a tertiary care cancer hospital in Chennai, South India. Cases (N=31) were newly diagnosed, pre-treatment, biopsy-confirmed, early-stage (<4 cm size) tongue cancers; further classified as early-onset (diagnosed at 20-49 years (N=12)) or late-onset cancers (diagnosed ≥50 years (N=19)), for secondary exploratory analyses. Cancer-free controls (N=31) were unrelated, and frequency matched to the cases on age and sex. Bacterial characterization of saliva was performed using 16S rRNA sequencing. Analysis (n=175 genera) included linear regression for α-diversity, constrained analysis of principal coordinates, permutational multivariable analysis of variance for β-diversity, and analysis of compositions of microbiomes with bias correction for taxa abundance. We also examined differences in established bacterial pathogens selected a priori. The median age of participants was 52 years and a third were women. While there was no difference in α-diversity, β-diversity showed distinct clustering of bacterial genera in controls, early-onset, and late-onset cases. In overall and early-onset cases (vs. controls), genera Eikenella and Campylobacter showae were enriched. Further, in early-onset cases (vs. controls), genera Alloprevotella, Comamonas, Aggregatibacter were enriched, Oribacterium was depleted, and W5053 had differentially absent patterns. Beyond the established pathogens, this study offers important leads for future etiological investigations, particularly in exploratory analyses of early-onset tongue cancers in the oral cavity.
Drug-resistant Neisseria gonorrheae is becoming an increasingly concerning threat as cases continue to rise, highlighting the need for novel therapeutics. We, therefore, have further developed our previously established structure-activity relationship for derivatives of acetazolamide, an FDA-approved carbonic anhydrase inhibitor. A large cohort of acetazolamide-based analogs was investigated for their activity against N. gonorrheae and their binding to NgCAs. Lead compounds were carried forward for in vitro ADME evaluation before prioritizing two molecules, 18 and 33, for in vivo PK analysis. These compounds were orally bioavailable and metabolically stable, and exhibited low cytotoxicity against mammalian cell lines. When investigated for in vivo efficacy in an infected mouse model, 18 was found to significantly decrease gonococcal bioburden compared with the vehicle control. Our studies culminated in the finding that acetazolamide-based compounds can be developed as effective drugs against N. gonorrheae and may be an answer in the search for new therapeutics.
This study investigates a new regime of double-pulse resonance laser-induced breakdown spectroscopy (DP-RLIBS), that allows highly sensitive trace element detection with virtually no sample damage. In DP-RLIBS, a single laser pulse at a wavelength chosen to selectively excite a trace element of interest is split into two pulses: a direct pulse used for surface ablation and a delayed pulse used to excite the vapor generated by the direct pulse. We show that the new DP-RLIBS regime investigated here achieves a limit of detection (LoD) of 0.6 ppm for lead (excitation/fluorescence at 283.31/405.78 nm) and 0.8 ppm for iron (excitation/fluorescence at 296.69/373.49 nm) in copper samples using 100 laser shots, far exceeding the capabilities of conventional LIBS, which showed an LoD of 85 ppm for lead when both methods used the same energy of 600 μJ and the same number of laser shots. The DP-RLIBS technique provided accurate calibration curves with high linearity in the range of 0-1100 ppm for lead and a quadratic behavior for iron in the range 0-2100 ppm. Scanning electron microscopy (SEM) images confirmed the nondestructive nature of DP-RLIBS, showing no damage to the sample even after 10,000 laser shots, in contrast to the significant damage observed with conventional LIBS after only 100 shots. These results underscore the potential of DP-RLIBS for delicate analyses requiring high sensitivity and minimal impact on the sample.
Stomatal conductance, which is crucial for plant carbon assimilation and water regulation, is modulated by Ca2+-binding proteins (CBPs). These proteins mediate Ca2+ signaling transduction, transport and homeostasis, influencing various physiological processes including stomatal movement, pollen tube growth and hypocotyl elongation. Despite their significance, the involvement of CBPs in dark-induced stomatal closure remains elusive. Here, we investigated the role of Arabidopsis cytosolic Ca2+-binding protein 1 (CCaP1) in dark-induced stomatal closure. β-glucuronidase (GUS) staining and in situ hybridization confirmed its predominant expression in guard cells. Yeast one-hybrid and transient expression assays demonstrated that CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) directly binds to the CCaP1 promoter to negatively regulate its expression. Genetic studies demonstrated that CCaP1 regulated dark-induced stomatal closure. Furthermore, the use of the Ca2+ probe R-GECO1 has shown that CCaP1 affected cytosolic free Ca2+ ([Ca2+]cyt) levels and potassium ion (K+) uptake in guard cells under dark conditions. Our findings indicate that CCA1-regulated CCaP1 is essential for maintaining Ca2+ dynamics and normal K+ flux in dark-induced stomatal closure.
Chemical extrasynaptic signaling in the mammalian brain is involved in the control of behavior via modulation of neural activity, in wiring the brain by directing the axonal growth, in localization of pharmacological effects of drugs, and in regulating the neuroinflammation. Local gradients of various neurochemicals in the brain are difficult to study in vivo due to their complex spatiotemporal dynamics induced by intricate interactions between neurons and glial cells that are not well understood. Here, to directly measure in vivo gradients of multiple neurotransmitters and metabolites simultaneously, we utilize an open-flow silicon nanodialysis sampling platform coupled with sensitive mass spectrometry. Results reveal strong millimeter-scale spatial gradients in concentration of neurotransmitters, neuromodulators, and astroglial modulators in a mouse cortex. Formation and maintenance of such local chemical compartments indicate strong regulation of brain neurochemistry by glial-neuron interactions that may heavily influence physiological and pathophysiological modulation of brain functions.
Chronic spine pain is linked to self-reported cognitive complaints. However, objective markers are lacking. The 90-s Continuous Visual Attention Test (CVAT) quantifies key attention subdomains: reaction time (RT, alertness), RT variability (VRT, sustained attention), omission errors (focused attention) and commission errors (impulsivity). This study aimed to identify which specific attentional subdomains, measured by the CVAT, are impaired in adults with chronic spine pain. This prospective case-control study included 84 adults with chronic lumbar/cervical pain (≥ 3 months) and 118 healthy controls. A MANCOVA tested group differences on CVAT variables, controlling for age and sex, followed by Bonferroni-corrected ANCOVAs. To isolate cognitive variability from general processing speed, the coefficient of variability (VRT/RT) was also analysed. Logistic regression assessed the predictive power of CVAT indices for pain status. The MANCOVA showed a significant group effect (Pillai's Trace = 0.46, F(4,195) = 41.43, p < 0.001). Patients exhibited impairments in all measures p < 0.001 (η2 = 0.093-0.44). The VRT deficit persisted when using VRT/RT. Logistic regression identified VRT as the strongest predictor of chronic spine pain (χ2(1) = 147.53, p < 0.001), correctly classifying 86.6% of participants. This finding remained when using VRT/RT (χ2(1) = 130.55, p < 0.001; 82.7% accuracy). Patients with chronic spine pain demonstrate attentional deficits, with sustained attention instability (VRT and VRT/RT) as the most robust marker. The CVAT detects this impairment, offering a practical tool for clinical assessment to inform treatment and monitor cognitive function in pain management. III (prospective case-control). A brief, 90-s computerized attention test provides an objective, clinic-ready screen for sustained-attention instability in spine pain patients. Identifying cognitive vulnerability at the point of care can inform perioperative counselling, driving/work-safety guidance and rehabilitation planning, and it may help monitor treatment response alongside pain metrics, offering a noninvasive, nonpharmacologic complement to standard pain assessment.
Aortic valve calcification (AVC) is the primary process leading to aortic stenosis. We examined whether polygenic risk scores (PRS) are associated with AVC beyond traditional atherosclerotic cardiovascular disease risk factors. We included 6812 participants in MESA (Multi-Ethnic Study of Atherosclerosis) with computed tomography-measured AVC at Visit 1. Using previously published PRS we calculated weighted PRS, standardized within each ancestry group. The cross-sectional association per 1 SD higher PRS with AVC >0 was examined using multivariable logistic regression modeling with Bonferroni correction. The mean age was 62 years old, 53% were female, and 913 (13.4%) had AVC >0 at baseline. The PRS for coronary artery disease (hazard ratio [HR], 1.16 [95% CI, 1.07-1.26]), systolic blood pressure (HR, 1.1 [95% CI, 1.020-1.2]), low-density lipoprotein cholesterol (HR, 1.16 [95% CI, 1.06-1.25]), and lipoprotein(a) (HR, 1.11 [95% CI, 1.02-1.20]) were significantly associated with AVC, whereas the other PRS including coronary artery calcium (HR, 1.02 [95% CI, 0.94-1.10]) and C-reactive protein (HR, 0.97 [95% CI, 0.89-1.05]) were not. In sex-stratified analyses, the PRS for coronary artery disease, low-density lipoprotein cholesterol, and lipoprotein(a) were significantly associated with AVC >0 for both sexes (P<0.05), whereas the systolic blood pressure PRS was borderline significant for women (HR, 1.10 [95% CI, 0.97-1.25]) and significant for men (HR, 1.11 [95% CI 1.00-1.24]). Our results confirm the role of atherogenic lipids in the pathogenesis of AVC and suggest that systolic blood pressure and the genetic risk factors for CAD are also important risk factors. The lack of association for the coronary artery calcium PRS with AVC >0 strongly suggests significant differences exist in the calcification pathways for AVC and coronary artery calcium.
Adrenal vein sampling (AVS) is the standard of care for guiding surgery in primary aldosteronism (PA). Because of its technical complexity and limited availability, however, many centers still use cross-sectional imaging for surgical guidance. Single referral-center retrospective cohort study of patients with PA who underwent unilateral adrenalectomy between 2012-2024. Blinded cross-sectional imaging interpretation was corroborated with CYP11B2 immunohistochemistry (IHC) of formalin-fixed paraffin-embedded adrenal tissue. Of 173 patients, age 52.6±11.8 years, 119 (68.8%) were men, 134 (77.5%) White, 30 (17.3%) Black, and 9 (5.2%) other races. CYP11B2 IHC identified a single aldosterone-producing adenoma (APA) or nodule (APN) in 87 (50.3%) and 38 (22.0%) patients, respectively; multiple CYP11B2-positive foci in 45 (26.0%) patients, and no CYP11B2-positive lesions in 3 patients. A single corresponding APA or APN on both IHC and imaging was found in only 53/173 (31%) patients, and an additional 38/173 (22%) patients also had adrenal thickening. Discrepant IHC-imaging findings were observed in 82 (47.4%) patients, including: 1) additional nodule(s) on imaging (ipsilateral non-functional adenoma, n=21; bilateral nodules, n=29; or contralateral nodule(s), n=6); 2) normal adrenals (n=2) or unilateral adrenal hyperplasia (n=4), but discrete CYP11B2-positive foci on IHC; and 3) corresponding APA/APN on imaging-IHC with additional CYP11B2-positive area(s) (n=20). Patients with IHC-imaging concordance had the highest proportion of women and KCNJ5 mutations, while CACNA1D mutations were most frequent in the discordant group. Even in patients with lateralized PA, IHC mapping of aldosterone sources corresponded with imaging findings in approximately half of the cases. These data caution against targeted therapy guided by cross-sectional imaging.
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