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Abstract Protein complexes are fundamental to all cellular processes, so understanding their evolutionary history and assembly processes is important. Gene duplication followed by divergence is considered a primary mechanism for diversifying protein complexes. Nonetheless, to what extent assembly of present-day paralogous complexes has been constrained by their long evolutionary pathways and how cross-complex interference is avoided remain unanswered questions. Subunits of protein complexes are often stabilized upon complex formation, whereas unincorporated subunits are degraded. How such cooperative stability influences protein complex assembly also remains unclear. Here, we demonstrate that subcomplexes determined by cooperative stabilization interactions serve as building blocks for protein complex assembly. We further develop a protein stability-guided method to compare the assembly processes of paralogous complexes in cellulo. Our findings support that oligomeric state and the structural organization of paralogous complexes can be maintained even if their assembly processes are rearranged. Our results indicate that divergent assembly processes by paralogous complexes not only enable the complexes to evolve new functions, but also reinforce their segregation by establishing incompatibility against deleterious hybrid assemblies.

Fine-grain copper (Cu) films (grain size: 100.36 nm) with a near-atomic-scale surface (0.39 nm) were electroplated. Without advanced post-surface treatment, Cu–Cu direct bonding can be achieved with present-day fine-grain Cu films at 130℃ in air ambient with a minimum pressure of 1 MPa. The instantaneous growth rate on the first day is 164.29 nm d−1. Also, the average growth rate (∆R/∆t) is evaluated by the present experimental results: (i) 218.185 nm d−1 for the first-day period and (ii) 105.58 nm d−1 during the first 14-day period. Ultrafast grain growth and near-atomic-scale surface facilitate grain boundary motion across the bonding interface, which is the key to achieve Cu–Cu direct bonding at 130℃ in air ambient.

BackgroundThe role of routine intravascular imaging in percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) remains unclear. This study evaluated the clinical outcomes of PCI guided by different imaging modalities in AMI patients.Materials and methodsData from AMI patients who had undergone PCI between 2012 and 2022 were analyzed. The mean follow-up was 12.9 ± 1.73 months. The imaging modality-either intravascular ultrasound (IVUS), optical coherence tomography (OCT), or angiography alone-was selected at the operator's discretion. The primary endpoint was major adverse cardiac events (MACEs), including cardiovascular (CV) death, myocardial infarction (MI), target vessel revascularization.ResultsOf the 1,304 PCIs performed, 47.5% (n = 620) were guided by angiography alone, 37.0% (n = 483) by IVUS, and 15.4% (n = 201) by OCT. PCI guided by intravascular imaging modalities was associated with lower 1-year rates of MI (1.3%, P = 0.001) and MACE (5.2%, P = 0.036). OCT-guided PCI was linked to lower rates of 1-year CV death (IVUS vs. OCT: 6.2% vs. 1.5%, P = 0.016) and MACE (IVUS vs. OCT: 6.4% vs. 2.5%, P = 0.032). Intravascular imaging modalities and diabetes were identified as predictors of better and worse 1-year MACE outcomes, respectively.ConclusionPCI guided by intravascular imaging modalities resulted in improved 1-year clinical outcomes compared to angiography-guided PCI alone in AMI patients. OCT-guided PCI was associated with lower 1-year MACE rates compared to IVUS-guided PCI. Therefore, intravascular imaging should be recommended for PCI in AMI, with OCT being particularly considered when appropriate.

Abstract Aims Patients with high‐flow arteriovenous (AV) access are at risk of developing high‐output cardiac failure (HOCF) and subsequent hospitalization. However, diagnosing HOCF is challenging and often requires invasive procedures. The role of systemic vascular resistance (SVR) in diagnosing HOCF is underestimated, and its predictive value is limited. Our study aims to identify non‐invasive risk factors for HOCF to facilitate early diagnosis and timely surgical interventions. Methods and results We included 109 patients with high‐flow AV access who underwent serial echocardiography. The retrospective cohort was divided into two groups based on their hospitalization due to HOCF. The two groups were matched for age and gender. After a mean follow‐up of 25.1 months, 19 patients (17.4%) were hospitalized due to HOCF. The two groups had similar baseline characteristics. However, the HOCF group had a higher value of vascular access blood flow (Qa) (2168 ± 856 vs. 1828 ± 617 mL/min; P = 0.045). Echocardiographic analysis revealed that the HOCF group had more pronounced left ventricular diastolic dysfunction (E/e′: 21.1 ± 7.3 vs. 16.2 ± 5.9; P = 0.002), more severe pulmonary hypertension (right ventricular systolic pressure: 41.4 ± 16.7 vs. 32.2 ± 12.8; P = 0.009), a higher Doppler‐derived cardiac index (CI) (4.3 ± 0.8 vs. 3.7 ± 1.1; P = 0.031), and a lower Doppler‐derived estimated SVR (eSVR) value (5.5 ± 0.3 vs. 6.9 ± 0.2; P = 0.002) than the non‐HOCF group. Using multivariable Cox regression analysis, a low eSVR value (

Objective: Leveraging patient data through machine learning techniques in disease care offers a multitude of substantial benefits. Nonetheless, the inherent nature of patient data poses several challenges. Prevalent cases amass substantial longitudinal data owing to their patient volume and consistent follow-ups, however, longitudinal laboratory data are renowned for their irregularity, temporality, absenteeism, and sparsity; In contrast, recruitment for rare or specific cases is often constrained due to their limited patient size and episodic observations. This study employed self-supervised learning (SSL) to pretrain a generalized laboratory progress (GLP) model that captures the overall progression of six common laboratory markers in prevalent cardiovascular cases, with the intention of transferring this knowledge to aid in the detection of specific cardiovascular event. Methods and procedures: GLP implemented a two-stage training approach, leveraging the information embedded within interpolated data and amplify the performance of SSL. After GLP pretraining, it is transferred for target vessel revascularization (TVR) detection. Results: The proposed two-stage training improved the performance of pure SSL, and the transferability of GLP exhibited distinctiveness. After GLP processing, the classification exhibited a notable enhancement, with averaged accuracy rising from 0.63 to 0.90. All evaluated metrics demonstrated substantial superiority ( ${p} < 0.01$ ) compared to prior GLP processing. Conclusion: Our study effectively engages in translational engineering by transferring patient progression of cardiovascular laboratory parameters from one patient group to another, transcending the limitations of data availability. The transferability of disease progression optimized the strategies of examinations and treatments, and improves patient prognosis while using commonly available laboratory parameters. The potential for expanding this approach to encompass other diseases holds great promise. Clinical impact: Our study effectively transposes patient progression from one cohort to another, surpassing the constraints of episodic observation. The transferability of disease progression contributed to cardiovascular event assessment.

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Background: Platelets, a type of anucleated cell, play a crucial role in cardiovascular diseases (CVDs). Therefore, targeting platelet activation is essential for mitigating CVDs. Endogenous agonists, such as collagen, activate platelets by initiating signal transduction through specific platelet receptors, leading to platelet aggregation. Eugenol, primarily sourced from clove oil, is known for its antibacterial, anticancer, and anti-inflammatory properties, making it a valuable medicinal agent. In our previous study, eugenol was shown to inhibit platelet aggregation induced by collagen and arachidonic acid. We concluded that eugenol exerts a potent inhibitory effect on platelet activation by targeting the PLCγ2–PKC and cPLA2-TxA2 pathways, thereby suppressing platelet aggregation. In our current study, we found that eugenol significantly inhibits NF-κB activation. This led us to investigate the relationship between the NF-κB and cPLA2 pathways to elucidate how eugenol suppresses platelet activation. Methods: In this study, we prepared platelet suspensions from the blood of healthy human donors to evaluate the inhibitory mechanisms of eugenol on platelet activation. We utilized immunoblotting and confocal microscopy to analyze these mechanisms in detail. Additionally, we assessed the anti-thrombotic effect of eugenol by observing fluorescein-induced platelet plug formation in the mesenteric microvessels of mice. Results: For immunoblotting and confocal microscopy studies, eugenol significantly inhibited NF-κB-mediated signaling events stimulated by collagen in human platelets. Specifically, it reduced the phosphorylation of IKK and p65 and prevented the degradation of IκBα. Additionally, CAY10502, a cPLA2 inhibitor, significantly reduced NF-κB-mediated signaling events. In contrast, BAY11-7082, an IKK inhibitor, did not affect collagen-stimulated cPLA2 phosphorylation. These findings suggest that cPLA2 acts as an upstream regulator of NF-κB activation during platelet activation. Furthermore, both BAY11-7082 and CAY10502 significantly reduced the collagen-induced rise in intracellular calcium levels. In the animal study, eugenol demonstrated potential as an anti-thrombotic agent by significantly reducing platelet plug formation in fluorescein-irradiated mouse mesenteric microvessels. Conclusion: Our study uncovered a novel pathway in platelet activation involving the cPLA2-NF-κB axis, which plays a key role in the antiplatelet effects of eugenol. These findings suggest that eugenol could serve as a valuable and potent prophylactic or therapeutic option for arterial thrombosis.

The prevalence of patients with primary aldosteronism (PA) is about 5%–15% in hypertensive patients, and it is common cause of secondary hypertension in clinical practice. Two major causes of PA are noted, namely bilateral adrenal hyperplasia and aldosterone-producing adenoma, and the general diagnosis is based on three steps: (1) screening, (2) confirmatory testing, and (3) subtype differentiation (Figure 1). The recommendation for screening patients is at an increased risk of PA, here we focus on which patients should be screened for PA, not only according to well-established guidelines but for potential patients with PA. We recommend screening for 1) patients with resistant or persistent hypertension, 2) hypertensive patients with hypokalemia (spontaneous or drug-induced), 3) young hypertensive patients (age

Aims. We aimed to evaluate the acute performance and short- and long-term outcomes of optical coherence tomography (OCT)-guided Magmaris deployment. Methods. This was a retrospective study of 28 consecutive patients (23 men, mean age: 59.8 years) with 28 Magmaris implantations in de novo coronary lesions. OCT was performed at the baseline and after the final postdilatation. The choice of stent and postdilatation balloon size was based on OCT measurements. The following indices were determined using OCT: prestenting minimum lumen diameter and area, poststenting minimum lumen diameter and area, acute lumen area gain, residual area stenosis, eccentricity and symmetry indices, incomplete strut apposition, strut fracture, tissue prolapse, and edge dissection. Results. Before the stenting, OCT analysis revealed a minimal lumen area of 1.55 ± 0.59 mm2, a minimal lumen diameter of 1.19 ± 0.38 mm, a minimal scaffold area of 6.78 ± 1.58 mm2, and a minimal scaffold diameter of 2.88 ± 0.50 mm2. The prolapse area was 1.2 ± 1.5 mm2. The mean percentage of RAS was 13.3 ± 7.1% and 6 (21.4%) patients had scaffold RAS more than 20%. Only one proximal edge intimal dissection was noted. The mean eccentricity index was 0.86 ± 0.04 and symmetry index 0.33 ± 0.08. ISA analysis showed that the percentage of malapposed struts was 1.5%. There were no short-term cardiovascular events, and only 2 incidents of target lesion failure (TLF) occurred 13 months later. Conclusion. The Magmaris has excellent acute mechanical performance and no short-term cardiovascular events occurred. There were only 2 TLFs that occurred 13 months later. It is suitable and feasible to treat vessels using the Magmaris.