Continuous and cuffless blood pressure (BP) estimation using
photoplethysmography (PPG) has considerable potential for wearable
health monitoring. However, PPG records peripheral optical
blood-volume-related changes rather than arterial pressure directly,
and its waveform is jointly shaped by systemic hemodynamics, local
vascular regulation, sensor--tissue interaction, and measurement
conditions. Consequently, high predictive performance does not
necessarily establish that a model has learned physiologically valid or
mechanism-specific BP information. To address this gap, we propose a
physiology- and measurement-informed framework for evaluating
PPG-derived descriptors and representations. Rather than treating
features as direct measurements of isolated cardiovascular
mechanisms, the framework organizes them into four non-exclusive physiological sensitivity domains-cardiac pump-related dynamics, arterial compliance-related dynamics, wave-reflection-related morphology, and peripheral vascular regulation-along with a fifth distinct category for integrative composite representations. Drawing on a qualitative synthesis of 87 studies guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), representative descriptors are examined in terms of their directly observed signal properties, candidate physiological sensitivities, mechanism specificity, susceptibility to confounding, calibration dependence, wearable observability, and the evidential basis and limitations of their proposed interpretations. Importantly, the supporting literature provides uneven and often indirect validation of the assumed relationships between peripheral blood-volume-related signals, arterial pressure or flow, and specific hemodynamic mechanisms. Particular attention is given to practical limitations such
as heart-rate dependence, temperature, contact pressure, measurement
site, and the loss of morphological landmarks in reflective wearable
PPG. A brief illustrative audit of a published feature-guided hybrid
model is retained as an example of how the framework can distinguish
model use of physiologically motivated descriptors from physiological
validation. The proposed framework does not establish or validate PPG
as a direct or mechanism-specific measure of BP; rather, it organizes
the heterogeneous and incompletely validated physiological and
measurement assumptions reported in the literature. It
provides a structured basis for identifying conditions under which
BP-related information may be observable and for defining stronger
validation requirements for cuffless BP estimation systems.

Gastrin regulates gastric acid secretion and mucosal homeostasis via the cholecystokinin-2 receptor (CCK2R). Aberrant signaling via CCK2R (cholecystokinin family) and the distinct class A GPCR, gastrin-releasing peptide receptor (GRPR; bombesin family), drives oncogenesis across diverse GI and non-GI malignancies through calcium mobilization, MAPK/PI3K activation, EGFR transactivation, and constitutive splice variants like CCK2Ri4sv. Furthermore, precursor forms such as progastrin remodel the tumor microenvironment by interacting with non-CCK binding sites (p78, Annexin A2), converting fibroblasts into pro-invasive CAFs and sustaining cancer stem cells. Chronic hypergastrinemia, induced by Helicobacter pylori infection, autoimmune gastritis, or long-term proton pump inhibitor (PPI) therapy, drives enterochromaffin-like (ECL) cell hyperplasia, promoting gastric neuroendocrine tumors and diffuse-type carcinomas. Beyond gastroenteropancreatic physiology, selective expression of CCK2R on ECL and thyroid C-cells, combined with widespread ectopic GRPR overexpression in solid tumors, establishes versatile platforms for molecular imaging and radiotheranostics. Radiolabeled peptide antagonists and stabilized minigastrin/bombesin analogs conjugated to diagnostic (68Ga, 64Cu) or therapeutic radionuclides (177Lu,225Ac, 212Pb) enable high-resolution PET imaging and targeted radionuclide therapy (PRRT/TAT). These strategies demonstrate high diagnostic accuracy and localized cytotoxicity in medullary thyroid carcinoma, small cell lung cancer, prostate neoplasms, and ER+ breast cancers. Concurrently, novel circulating biomarkers, including multi-genomic liquid biopsies (NETest®) and ProGRP, significantly improve non-invasive disease tracking. Unraveling these receptor pathways bridges tumor biology with translational medicine, offering transformative potential for personalized diagnosis, risk stratification, and targeted radionuclide therapy.

Thrombotic diseases continue to pose a significant clinical challenge with high mortality and recurrence rates following thrombolysis. Herein, we propose endogenous shear stress-activated tribocatalytic thrombolysis via a dynamic S-scheme heterojunction and thrombosis recurrence-prevention via cascade nanozyme catalysis. Specifically, deformable yolk-shell nanoparticles (NPs) composed of bismuth ferrite-coated flexible mesoporous organosilica (fBF) yolks and manganese-doped cerium oxide (CeMn) shells, with fucoidan subsequently grafted onto the surface, are referred to as fBF@CeMn-Fu. Local shear stress induces high-frequency friction and collision between the fBF yolks and the CeMn shells, and tribocatalytic activity is promoted through friction contact area expansion via the deformability of mesoporous organosilica, S-scheme heterojunction between fBF and CeMn, and Mn-O-Ce electron channel and oxygen vacancies in CeMn. These deformability/component engineering and tribovoltaic/piezoelectric effect collectively boost electron-hole separation, overall redox capacity and generation of reactive oxygen species for effective thrombus dissolution. Upon completion of thrombolysis, Mn doping acts as a bidirectional electron pump, accelerating electron transfer and augmenting the superoxide dismutase (SOD) and catalase (CAT) activity of CeMn nanozyme. This SOD-CAT cascade catalysis effectively mitigates oxidative stress and inflammatory microenvironment associated with thrombosis, laying a foundation to prevent thrombosis recurrence. In a carotid artery thrombosis model, combination of tribocatalysis and fucoidan grafting achieve nearly complete thrombus dissolution. Subsequently, nanozyme cascade catalysis restores endothelial function, upregulates nitric oxide synthase expression, promotes endothelial healing, thereby suppressing platelet activation and thrombosis recurrence. The deformable yolks-enhanced tribocatalysis and nanozyme cascade offer an effective strategy for thrombosis management with precise dissolution and recurrence prevention.

Optimized bismuth quadruple therapy is a recommended first-line treatment for Helicobacter pylori infection but is limited by regimen complexity, whereas tegoprazan-amoxicillin dual therapy has emerged as a simplified alternative with limited comparative evidence. We conducted a systematic review and meta-analysis of randomized controlled trials comparing tegoprazan-amoxicillin dual therapy with bismuth-containing quadruple therapy (BQT) as first-line treatment for H. pylori infection. Electronic databases (PubMed, Embase, Web of Science Core Collection, and the Cochrane Library) were searched from inception through 24 December 2025. Intention-to-treat eradication rates were pooled using a random-effects model. Sensitivity analyses were performed by restricting comparators to proton pump inhibitor-based BQT. Safety outcomes were qualitatively synthesized. Five randomized controlled trials involving 1541 treatment-naïve participants were included. In intention-to-treat analyses, 14-day tegoprazan-amoxicillin dual therapy showed no statistically significant difference in eradication efficacy compared with BQT [risk ratio, 0.996; 95% confidence interval, 0.911-1.089; P = 0.93]. Sensitivity analysis restricted to proton pump inhibitor-based BQT yielded consistent results (risk ratio, 0.985; 95% confidence interval, 0.877-1.107; P = 0.80). Across individual studies, adverse events and treatment discontinuation were generally reported more frequently in BQT arms than in dual-therapy arms, although reporting of safety and adherence outcomes was not fully standardized. In randomized first-line trials, 14-day tegoprazan-amoxicillin dual therapy demonstrated eradication efficacy comparable to BQT. These findings suggest that 14-day tegoprazan-amoxicillin dual therapy may serve as an alternative first-line option, particularly when regimen simplicity and tolerability are prioritized.

We report on the design and operational characterization of a femtosecond time-resolved Bragg coherent X-ray diffraction imaging (tr-BCDI) setup at the XSS beamline of PAL-XFEL, aimed at enabling direct nanoscale visualization of ultrafast lattice dynamics in individual nanocrystals. The pump-probe temporal resolution was evaluated via time-resolved X-ray diffraction measurements on a Bi (003) epitaxial thin film, confirming a timing precision better than 60 fs through the observation of coherent phonon oscillations. The static coherent imaging capability was benchmarked by reconstructing three-dimensional displacement fields of Au and zeolite nanocrystals, achieving spatial resolutions of 32.3 nm and 50.3 nm, respectively. Crucially, the time-resolved imaging capability was directly demonstrated by tracking the ultrafast structural response of a zeolite nanocrystal under femtosecond laser excitation, successfully capturing the transient shift of the Bragg peak and the corresponding projection of the displacement fields through two-dimensional phase retrieval at a fixed angular condition. These results collectively establish the XSS tr-BCDI setup as a reliable and complementary framework within the global landscape of XFEL facilities, providing direct access to femtosecond-scale structural dynamics in crystalline nanomaterials.

The 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for managing patients with acute coronary syndromes (ACS) is the first major update since the 2013-2015 ST-elevation myocardial infarction (STEMI) and non-ST elevated myocardial infarction (NSTEMI) guidelines. It brings both conditions together into a single framework. This review covers the most important new and revised recommendations and points out where evidence is still lacking.

We here describe a procedure for the calculation of PE spectra in solution, including vibrational and dynamical solvent effects. Steady-state vibronic spectra are computed in the harmonic approximation, including the effect of the electronic continuum on the cross section. Solvent effects are described in the framework of continuum polarizable models, providing an accurate assessment of dynamical solvation effects, crucial for a reliable modelling of PE processes, with a very small computational cost. Time-resolved PE spectra are computed from the nonadiabatic quantum dynamics of the electronic-vibrational wavepacket propagating on the coupled valence states, described with a linear vibronic coupling model and adopting a semiclassical approximation. Our approach provides accurate steady-state PE spectra for 9(H)adenine in the gas phase and adenosine in water. In the former case, the position, the relative energy and the dependence on the PE ejection angle for the three lowest-energy bands are in good agreement with the experimental ones. We simulated the pump-probe PE spectrum of adenosine in water using both static and dynamical approaches, obtaining spectra fully consistent with the experimental ones and getting new insights on its sub-ps photophysics. Some methodological issues in the simulation of PE spectra in solutions are also discussed.

Autotaxin (ATX) is a secreted lysophospholipase D that generates lysophosphatidic acid (LPA). We investigated circulating ATX activity and blood pressure (BP) in rats throughout pregnancy. Systolic BP gradually decreased after gestational day 15, reached a nadir on day 21, and rebounded on day 1 postpartum. Conversely, plasma ATX activity rose from day 12 through days 19-21 and declined thereafter. A bolus intravenous LPA injection on day 21 significantly increased BP. Although a single anti-ATX serum injection on day 21 showed little acute effect, continuous administration via osmotic mini-pump from day 18 significantly delayed the late-gestational BP drop. These results demonstrate a novel inverse relationship between circulating ATX activity and BP in late-pregnant rats.

ObjectiveProton pump inhibitors (PPIs) are prescribed in the intensive care unit (ICU), but their association with outcomes in patients with pulmonary fibrosis remains unclear.MethodsWe conducted a retrospective cohort study using the Medical Information Mart for Intensive Care IV (MIMIC-IV) database (v3.1). Propensity score matching (PSM) and multivariate regression models adjusted for baseline differences. Landmark, subgroup, dose-response, and exploratory drug-specific analyses were performed.ResultsAmong 551 patients, 286 (51.9%) received PPIs. After PSM, PPI use was associated with higher 30-day mortality (HR 1.59, 95% CI 1.08-2.34; p = 0.019), 90-day mortality (HR 1.62, 95% CI 1.15-2.30; p = 0.006), ICU mortality (OR 3.22, 95% CI 1.57-6.59; p = 0.001), and longer ICU stay (β 1.90, 95% CI 0.91-2.88; p < 0.001). Associations weakened in the 48-hour landmark analysis, with only 90-day mortality remaining significant (adjusted HR 1.40, 95% CI 1.02-1.90; p = 0.035). Exploratory drug-specific estimates varied across agents but were imprecise. In exploratory cumulative-dose analyses after PSM and adjustment, each 10-mg increase in omeprazole-equivalent exposure was associated with higher ICU mortality (OR 1.06, 95% CI 1.01-1.10; p = 0.012) and longer ICU stay (β 0.34 days, 95% CI 0.28-0.40; p < 0.001), but not 30-day or 90-day mortality. Initial timing was not associated with mortality after PSM and adjustment but was associated with longer ICU stays. Subgroup associations were consistent, with an interaction between PPI and H2RA use for ICU length of stay.ConclusionsPPI exposure was associated with higher short-term mortality and longer ICU stay, although the associations weakened in the 48-hour landmark analysis, with only 90-day mortality remaining significant. Higher cumulative PPI doses were associated with higher ICU mortality and longer ICU stay. These findings are hypothesis-generating and require prospective confirmation before informing changes in clinical practice.

Drug-induced liver injury (DILI) remains a major cause of preclinical and clinical attrition, reflecting persistent gaps in the predictive translation of preclinical safety data to human outcomes. To address these gaps, we established a refined multiparametric framework for early DILI risk prediction using a balanced reference set of 170 drugs with established clinical outcomes. Thirty physicochemical, mechanistic endpoints and exposure-related features were systematically evaluated to identify high-specificity predictors of intrinsic DILI risk. Cytotoxicity in primary human hepatocytes and human liver microtissues, mitochondrial toxicity (i.e., mitotoxicity) and bile salt export pump inhibition were identified as top predictive features. Incorporation of clinical exposure data to derive margins of safety substantially improved assay performance, emphasizing the importance of exposure normalization. A multiparametric, flag-based hazard framework integrating ≥ 2 hazard flags achieved 98% specificity and a positive likelihood ratio of 18, providing a pragmatic approach for early compound triage and confidence in early decision making. Random Forest models further enhanced predictive performance, identifying exposure, predicted lipophilicity (e.g., cLogD), mitotoxicity, cytotoxicity and hepatic clearance as major contributors to DILI risk, with exposure-informed models achieving a balanced accuracy of 0.72. Application of the framework to contemporary Genentech portfolio molecules demonstrated translational utility in refining risk categorization and distinguishing between borderline or 0-1 flag compounds. Collectively, this work establishes a mechanistically informed and machine learning-enabled platform that combines interpretability, specificity and practicality to guide safer molecule design in drug discovery and reduce hepatotoxicity-related attrition in clinical development.

C. auris is an emerging multidrug-resistant (MDR) fungal pathogen that poses an urgent threat to global public health. It is characterized by rapid nosocomial transmission, persistent environmental survival, and extensive cross-resistance to conventional antifungal therapies. This comprehensive narrative review bridges the fundamental molecular mechanisms of intrinsic and acquired antifungal resistance with host adaptation strategies and emerging clinical interventions. C. auris resistance is driven by a highly sophisticated network of genetic mutations and metabolic reprogramming distributed across six geographically distinct clades (I-VI), including the newly identified Clade VI from the Indomalayan zone. Azole resistance primarily relies on clade-specific point mutations in the target gene ERG11, synergistically amplified by TAC1b-driven transcriptional upregulation of the CDR1 efflux pump. Echinocandin resistance is predominantly mediated by conformational reshaping across three distinct hotspot regions of the FKS1 gene, bolstered by Hsp90-mediated stress compensatory networks. For polyenes, while clinical resistance is frequently overestimated by commercial assays, true tolerance mechanisms involved the depletion of target ergosterol and profound non-sterol-dependent sphingolipid remodeling. Beyond genomic modifications, C. auris exhibits significant phenotypic plasticity, forming robust, polysaccharide-rich biofilms on indwelling medical devices that confer profound physical drug tolerance. Clinically, the fungus demonstrates a strong cutaneous tropism-predominantly colonizing the axilla and groin-which acts as the primary reservoir for hospital outbreaks. Furthermore, experimental models reveal that C. auris actively exploits host immune deficiencies, specifically subverting the IL-17A/neutrophil/S100A8 axis, to evade immune clearance and establish persistent colonization. To overcome these formidable MDR bottlenecks, therapeutic paradigms are rapidly evolving. The integration of next-generation antifungals such as the long-acting echinocandin rezafungin, fosmanogepix, and ibrexafungerp, synergistic combination therapies, quorum-sensing inhibitors such as farnesol, and experimental nanocarrier delivery systems could represent promising frontiers to effectively dismantle the complex defense networks of C. auris.