Epidemiological studies have shown that lower activity of the cholesteryl ester transfer protein (CETP) correlates with reduced Alzheimer's disease (AD) risk. While small-molecule CETP inhibitors like evacetrapib have previously been assessed for cardiovascular diseases, their involvement in AD has not been investigated. Here, we establish CETP as a novel pharmacological target for AD treatment. Using CETP transgenic mice crossed to a mouse model of amyloidosis and administering evacetrapib, we provide evidence that CETP inhibition maintained memory independent of classic AD markers, likely through maintained vascular health, while increasing hippocampal cholesterol and altering plasma lipoproteins. Using proteomic data of cerebrospinal fluid (CSF) from cognitively unimpaired individuals at risk for AD in the PResymptomatic EValuation of Experimental or Novel Treatments for AD (PREVENT-AD) cohort, we confirm that our mouse model reflects physiological changes in pre-symptomatic human subjects. We propose the repurposing of CETP inhibitors as an effective therapeutic strategy to delay or prevent cognitive impairment in AD.

Panvascular diseases (PVDs) stand as the leading cause of global mortality, necessitating a paradigm shift from local anatomical repair to the systemic restoration of vascular homeostasis. While intravascular optical imaging has revolutionized diagnosis, it remains a passive observation tool, restricted by "physical bottlenecks" in resolution and "cognitive bottlenecks" in interpretation. To address these challenges, we frame our analysis around "Suitcordance", a concept aiming to capture the dynamic state of matching between interventional devices and the vascular microenvironment. In this review, we use Suitcordance as a working analytical framework to represent such a clinically-targeted, integrated perspective, and to organize the evidence on intravascular optical imaging and its integration with artificial intelligence. First, we summarize recent advances in intravascular imaging modalities, including micro-OCT, hybrid systems, and emerging detection technologies. Second, we review how AI-based image analysis and image-derived digital twin models are being applied to interpret these data and to support procedural decision-making. On this basis, we discuss how such tools may contribute to a more individualized assessment of device-vessel matching in panvascular disease.

Perioperative bleeding remains a major complication in cardiac surgery and is associated with increased morbidity, mortality, and transfusion requirements. While patient blood management strategies and goal-directed hemostatic therapies have improved outcomes, the role of fundamental physiological conditions such as acid-base balance, temperature, calcium homeostasis, and hematocrit remains underexplored in clinical research. These factors may critically modulate coagulation and influence the efficacy of hemostatic interventions. This comprehensive narrative review assesses the in vitro and in vivo impact of acidosis, hypothermia, hypocalcemia, and anemia on hemostasis and proposes the concept of a coagulation-friendly environment as a prerequisite for effective bleeding management in cardiac surgery. Optimization of these variables represents an essential foundation for effective hemostatic therapy and may improve bleeding outcomes when integrated into patient blood management strategies.

Upper-limb (UL) impairment following stroke significantly limits independence in activities of daily living (ADLs). Although tabletop functional task-oriented training (FTOT) is a cornerstone of neurorehabilitation, both conventional therapist-led and technology-supported FTOT face limitations in consistency, supervision, progression and continuity across settings. The objectives are to characterise current clinical practices in UL tabletop FTOT and identify stroke survivor-caregiver dyads' needs, constraints and support requirements across clinical and home contexts to inform user-centred technology development.

A multi-phase mixed-methods design will be employed. Phase-A will be an explanatory sequential design including a quantitative online survey of rehabilitation therapists (target minimum n=100) to characterise UL tabletop training delivery (eg, task selection, dose, progression). Survey findings will inform subsequent data collection through virtual qualitative interviews with a purposive subsample of therapists (anticipated n≈10-20) to examine task orchestration, adaptation and clinical decision-making in depth. Phase-B will use a descriptive qualitative design involving semi-structured interviews of stroke survivor-caregiver dyads (target n=15 dyads) to explore FTOT experiences across clinical and non-clinical contexts. Quantitative data will be analysed descriptively, and qualitative data will be analysed using inductive content analysis. Mixed-methods integration, within Phase-A and between the two phases, will examine convergence, complementarity, expansion and divergence. Integration will be illustrated using joint displays, visual tools that present the findings from both strands side-by-side using a table or figure. Patient and public involvement activities (n=5) and a pilot dyadic interview (two dyads) were completed to refine study materials and procedures.

Ethical approval was obtained from the Institutional Review Board of Christian Medical College, Vellore (IRB Min No. 2511113). Electronic informed consent will be obtained from therapists for the survey and qualitative interviews. Written informed consent will be obtained from the dyadic participants before the interviews. All study procedures will adhere to ethical principles for human research. Study findings will be disseminated through conference presentations and publication in peer-reviewed journals, with stakeholder-oriented dissemination to support clinical and technology development.

A simplified mitral valve transcatheter edge-to-edge repair (M-TEER) workflow under sole transesophageal echocardiographic (TEE) guidance, without fluoroscopy, has been developed. This study aimed to compare its real-world outcomes with the conventional procedures under the combined guidance of fluoroscopy and TEE.

We retrospectively analyzed 386 patients undergoing M-TEER between January 2021 and December 2025, including 286 in the Sole-TEE guidance group and 100 in the Combined guidance group. The primary endpoints were cardiovascular mortality, all-cause mortality, and a composite of all-cause mortality and heart failure hospitalization. Propensity score matching and overlap weighting were performed as sensitivity analyses.

Technical success was achieved in 98.3% and 97.0% of patients in the Sole-TEE and Combined guidance groups, respectively, and 30-day major adverse events occurred in 2.8% and 7.0%, respectively (p > 0.05). The median follow-up was 16.5 months. At 1 year, the estimated cumulative incidence rates of the three primary endpoints were 4.4%, 6.0%, and 11.3% in the Sole-TEE guidance group and 6.4%, 8.5%, and 11.3% in the Combined guidance group, respectively (p > 0.05). M-TEER failure at 1 year was 4.8% and 6.3%, respectively (p > 0.05). The corresponding adjusted hazard ratios (95% confidence intervals) for the three primary endpoints were 1.52 (0.61-3.79), 0.96 (0.42-2.18), and 0.93 (0.48-1.81), respectively. Findings were consistent in sensitivity and subgroup analyses.

In this real-world observational cohort, M-TEER performed under sole-TEE guidance was associated with favorable procedural and follow-up outcomes, supporting the feasibility of this simplified workflow in experienced centers.

The association of epicardial obstructive coronary artery disease with major adverse cardiovascular events (MACE) is established; however, accumulating evidence emphasizes the significant role of coronary microvascular dysfunction (CMD). The aim of this meta-analysis is to summarize the available evidence on the prognostic effect of CMD in cardiovascular outcomes and mortality.

Systematic literature search in MEDLINE/PubMed and Scopus was conducted to identify studies comparing the prognosis of CMD vs non-CMD using coronary flow reserve (CFR) and/or index of microcirculatory resistance (IMR) invasive indices. A meta-analysis to calculate pooled risk ratios (RR) was performed along with sensitivity and meta-regression analyses.

Thirty-one studies were included (n = 13,016, weighted mean age 58 years, males 57%, left ventricular ejection fraction 58%, CFR 2.6, IMR 24.4, CMD 33%). Meta-analysis of 24 studies (n = 8294) indicated a pooled RR for MACE of 2.55 (2.11, 3.10) for CMD vs non-CMD comparison. Consistent findings were observed for all-cause [1.88 (1.52, 2.33)] and cardiovascular mortality [2.76 (2.02, 3.76)], myocardial infarction [2.18 (1.56, 3.05)], revascularization [1.67 (1.06, 2.64)], heart failure hospitalization [3.46 (1.90, 6.30)], and stroke risk [1.85 (1.26, 2.71)]. The CFR and IMR-based analyses provided similar findings. Worse outcomes were observed in acute coronary syndrome patients and in those with the structural CMD endotype (abnormal CFR/abnormal IMR).

Invasively diagnosed CMD is associated with a 2.5-fold increase in MACE and a 3-fold increase in cardiovascular mortality. This finding highlights the importance of a more comprehensive assessment of coronary vasculature, including both the macro- and the microcirculation.

Antimicrobial resistance (AMR) is a serious threat to the human healthcare system due to the loss in efficacy of existing antibiotics, increasing mortality and morbidity, and higher treatment costs. Benzothiazole is a common scaffold in drug design, but no antimicrobial agents based on this scaffold structure are used clinically. In this study, a series of benzothiazole analogues were designed and synthesized as novel antibacterial agents. Among these analogues, compound 7k exhibited potent antibacterial activity against S. aureus (ATCC 29213), MRSA (ATCC BAA41), and MRSA (ATCC 43300) with a MIC value of 4 μg/mL. Under this concentration, compound 7k inhibited more than 80% of S. aureus biofilm formation. Notably, compound 7k showed low cell cytotoxicity (CC₅₀ > 200 μM), hemolytic activity (HC₅₀ > 200 μM), and high selectivity to the bacterial cell membrane. Mechanistic studies revealed that the bacterial cell membrane is the primary drug target of compound 7k. Moreover, compound 7k exhibited negligible skin toxicity and low acute oral toxicity. In vivo animal tests verified that compound 7k promoted the healing of infected skin wounds in mice. Taken together, compound 7k has therapeutic potential for clinical infections caused by MRSA strains.

Psoriasis is a chronic, immune-mediated inflammatory skin disorder. The vascular endothelium serves as the final barrier preventing circulating immune cells from entering inflamed skin, yet its role in psoriasis pathogenesis and therapeutic potential has long been overlooked. Here, we identify a pathogenic subpopulation of cyclooxygenase-2 (COX2, encoded by PTGS2) high endothelial cells (COX2⁺ ECs), characterized by elevated P-selectin expression, excessive oxidative stress, and MMP9-mediated glycocalyx degradation. The ROS-COX2-MMP9 axis can be effectively suppressed by mebendazole, an FDA-approved anthelmintic drug. Guided by this insight, we develop a bioinspired platform (P@Meb-MNs). Mebendazole and a P-selectin-targeting ligand (PSGL-1) spontaneously self-assemble into carrier-free nanoparticles, which are then encapsulated within an MMP9-responsive microneedle matrix. Upon transdermal administration, the microneedles penetrate the hyperkeratotic epidermis and degrade in response to elevated MMP9 levels, releasing P@Meb-NPs. Directed by PSGL-1, these nanoparticles selectively recognize and accumulate in COX2⁺ ECs, where mebendazole disrupts the ROS-COX2-MMP9 feedback loop, preserves glycocalyx integrity, and suppresses immune cell extravasation. This approach markedly enhances glycocalyx coverage from 11.91 ± 4.09% to 87.5 ± 8.7% and significantly reduces immune cell infiltration. Collectively, this work establishes a vascular-targeted therapeutic paradigm centered on endothelial glycocalyx repair and achieves precise and effective intervention in inflammatory diseases.

Immunohistochemistry is a tissue-based technique that enables in situ visualization of specific molecules, most commonly proteins or peptides, within preserved cellular and tissue architecture through antigen-antibody specificity. By using labeled antibodies, immunohistochemistry allows spatially resolved and cell type-specific detection of target molecules and maintains the morphological context, thereby providing both localization and relative expression information at the light or electron microscopy level. Owing to this integrative capacity, immunohistochemistry has become an essential tool in biological research and diagnostic pathology for characterizing molecular distribution and tissue organization across animal and plant systems. The detection techniques based on fluorescence and enzymes (chromogenic) are compared in terms of their repeatability, multiplexing capability, sensitivity, and specificity. With a focus on protocol standardization and methodological rigor, important procedural processes are covered, including fixation, antigen extraction, antibody optimization, signal detection, and quality control. Additionally, the immunohistochemistry technique remains essential for locating and identifying immunogenic substances in a variety of biological settings. Therefore, drawing on more than two decades of laboratory experience, this narrative review summarizes the history of the immunohistochemistry assay, its underlying principles and procedures, common immunohistochemistry protocol, methodological process, essential reagents, infrastructure, and best-practice principles required for the establishment and optimization of a high-quality immunohistochemistry laboratory.