Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high mortality rates. While previous studies have focused primarily on the epidemiological and clinical aspects of SFTS, indicators of renal injury at admission have received limited attention. We retrospectively analyzed 260 patients with SFTS admitted to the study hospital between April 1, 2023, and July 18, 2024, who were classified into the survival group (n = 163) and death group (n = 97) on the basis of 28-day prognosis. Renal-related data were collected upon admission. Univariate and multivariate Cox regression analyses were used to identify independent predictors, and a nomogram was constructed. Receiver operating characteristic (ROC) curves and calibration curves were used to assess the discrimination and calibration of the model. Kaplan–Meier curves were used to assess the cumulative survival rate of patients with these risk factors. External validation was conducted in 40 patients with SFTS who were admitted to an affiliated branch hospital during the same period. The 28-day mortality rate was 37.3

[This corrects the article DOI: 10.1016/j.bioactmat.2024.11.018.].

A 31-year-old female patient presented with a giant primary cardiac malignancy occupying the right atrium and invading the tricuspid valve and right ventricle. Due to the inoperability of the tumor by conventional surgery, heart transplantation was considered. However, the patient had a strongly positive panel reactive antibody (PRA), indicating a high risk of rejection. Our team performed an emergency heart transplantation and administered a combination of immunosuppressive therapies postoperatively. One month after the transplantation, the patient recovered smoothly and was discharged from the hospital. Despite giant cardiac sarcoma and high PRA-mediated rejection risk, tailored perioperative strategies, including aggressive desensitization, multimodal immunosuppression, and close surveillance, enabled successful transplantation and recovery. This highlights the feasibility of heart transplantation in select sarcoma cases with meticulous rejection management.

This study aimed to preliminarily investigate the feasibility, safety, and early clinical outcomes of minimally invasive left ventricular assist device (LVAD) implantation with concomitant cardiac procedures. We retrospectively analyzed the clinical data of three consecutive male patients with end-stage heart failure who underwent minimally invasive LVAD implantation at our center between August and November 2024. Two patients received the CorHeart 6 LVAD, while one received the CH-VAD LVAD. Two patients underwent concomitant procedures (patent foramen ovale closure or left atrial appendage occlusion) during the LVAD implantation. All procedures were successfully completed without intraoperative mortality or conversion to sternotomy. Cardiopulmonary bypass time ranged from 121 to 214 min. Postoperative echocardiography demonstrated reduced ventricular dimensions, improved ejection fraction, and resolution of significant valvular regurgitation in all patients. The duration of mechanical ventilation ranged from 1 to 5 days, and the ICU stay ranged from 3 to 7 days. No mortality, pump thrombosis, stroke, or reoperation for bleeding occurred. One patient experienced transient postoperative arrhythmia, which resolved with medical management. This initial experience suggests that minimally invasive LVAD implantation via left thoracotomy, with concomitant cardiac procedures, is technically feasible and safe in selected patients with end-stage heart failure. This strategy was associated with encouraging early outcomes and provides early clinical data on the minimally invasive application of devices such as the CorHeart 6 to the international LVAD community. What is known and what is new? What is the implication, and what should change now?

Constructing in situ tissue engineered heart valves based on xenogeneic decellularized heart valves (DHVs) is a promising strategy for heart valve regeneration. However, the inflammation triggered by foreign body responses results in maladaptive matrix remodeling and compromised mechanical support. Given the critical role of macrophages (M & oslash;s) in regulating several homeostasis to relieve xenogeneic rejection and promote tissue regeneration, folic acid modified cerium ions-tannic acid metal-polyphenol framework nanoparticles (FCT NPs) have been synthesized via a green coordination method and then loaded onto thiolated DHVs to reprogram macrophage phenotype. FCT NPs, with multiple enzyme-mimicking activity, biodegradability and biocompatibility, moderately scavenge various reactive oxygen species in M1 M & oslash;s, reprogramming them to increase the M2 phenotype. This reduces inflammatory factors levels and promotes secretion of anti-inflammatory and pro-regenerative cytokines, enabling elimination of inflammation and promotion of adaptive matrix remodeling. In vitro studies show that FCT-loaded DHVs (FCT@DHVs) exhibit excellent immunomodulatory capability, mechanical properties, hemocompatibility, and cytocompatibility. Rat implantation models reveal that FCT@DHVs achieve re-endothelialization and adaptive matrix remodeling via immunomodulation. They also exhibit excellent hemodynamics, hemocompatibility, histocompatibility, anti-calcification and mechanical support. Notably, M2 M & oslash;s numbers decrease with scaffold degradation, indicating self-adaptive immunomodulation. This strategy offers a promising approach for in situ heart valve regeneration based on xenogeneic DHVs.

Supercooling preservation holds great promise for extending the storage limits of organs. However, supercooled systems are susceptible to stochastic ice nucleation, which can cause fatal damage to the organs. In this study, an organogel interface composed of nanoscale polydimethylsiloxane and dimethyl‐silicone oil is proposed, which presents a significant energy barrier for ice nucleation, comparable to that of homogeneous nucleation. The organogel effectively eliminates primary ice nucleation sites, enabling a quasi‐homogeneous supercooling preservation system that does not rely on cryoprotectant agents or machine perfusion. Through a series of statistical experiments, this approach is demonstrated to be able to maintain stable supercooling and preserve mouse hearts at −4 °C for up to 72 h. A comprehensive assessment conducted at multiple scales indicates that the 36‐h supercooling preservation at −4 °C significantly mitigates cardiac injury by regulating mitochondrial structure and reducing metabolic rates. Utilizing a heart transplantation model with prognostic evaluations extending up to 3 months post‐transplantation, supercooling preservation within the quasi‐homogeneous system is confirmed, which can double the storage duration compared to clinically applied hypothermic preservation methods.

Valvular heart disease (VHD) poses a thorny problem in cardiovascular diseases. The most effective treatment for VHD is heart valve replacement. Biological heart valve (BHV) is more favored than mechanical heart valve due to the maturity of transcatheter heart valve replacement (THVR) and the absence of the need for lifelong anticoagulant use. However, traditional commercial BHV suffers degeneration within 10-15 years because of calcification caused by the cross-linking reagent, glutaraldehyde. Considering the remarkable properties of POSS, PEG, and the star-like eight-arm structure, we fabricated POSS-PEG-PP, which is a decellularized porcine pericardium (DPP) crosslinked by a star-like eight-arm cross-linker octafunctionalized POSS of benzaldehyde-terminated polyethylene glycol (POSS-PEG-CHO) based on the Schiff's base reaction. POSS-PEG-PP exhibits more intense fiber arrangement and better mechanical properties than GLUT-PP (glutaraldehyde crosslinked DPP). The results also show that the cytocompatibility, endothelialization, and hemocompatibility of POSS-PEG-PP are outstanding in vitro. Subsequently, in vivo assessments demonstrate that POSS-PEG-PP has anti-inflammatory and anti-calcification abilities. Furthermore, RNA sequencing analysis of subcutaneous implants suggests that the intervention of AMPK and IL-17 signaling pathways plays an important role in the inflammatory and immune responses regulation of POSS-PEG-PP. Therefore, POSS-PEG-PP is an excellent substitute material for BHVs and is expected to be clinically transformed.

MFG-E8 promotes oxidative stress by upregulating NOX4 and activating the MAPK pathway, which increases ROS production and affects vascular smooth muscle cell (VSMC) apoptosis, thereby driving the progression of abdominal aortic aneurysm (AAA). Resveratrol can inhibit the expression and function of MFG-E8, reduce ROS generation, and lower the incidence and severity of AAA, making it a potential therapeutic agent for AAA.

The technology of induced pluripotent stem cells (iPSCs) has enabled the conversion of somatic cells into primitive undifferentiated cells via reprogramming. This approach provides possibilities for cell replacement therapies and drug screening, but the potential risk of tumorigenesis hampers its further development and in vivo application. How to generate differentiated cells such as valvular endothelial cells (VECs) has remained a major challenge. Utilizing a combinatorial strategy of selective soluble chemicals, cytokines and substrate stiffness modulation, mouse embryonic fibroblasts are directly and efficiently transdifferentiated into induced aortic endothelial cell-like cells (iAECs), or human primary adult fibroblasts are transdifferentiated into induced valvular endothelial cell-like cells (hiVECs), without expressing pluripotency stem cell markers. These iAECs and hiVECs express VEC-associated genes and proteins and VEC-specific marker NFATC1 and are functional in culture and on decellularized porcine aortic valves, like mouse aortic endothelial cells or human primary aortic valvular endothelial cells. The iAECs and hiVECs seeded on decellularized porcine aortic valves stay intact and express VEC-associated proteins for 60 days after grafting into abdominal aorta of immune-compromised rats. In contrast, induced pluripotent stem cells (iPSCs) are less efficient in differentiating into VEC-like cells and pluripotency marker Nanog is expressed in a small subpopulation of iPSC-derived VEC-like cells that generate teratomas in SCID mice whereas hiVECs derived from transdifferentiation do not generate teratomas in vivo. Our findings highlight an approach to efficiently convert fibroblasts into iAECs and hiVECs and seed them onto decellularized aortic valves for safely generating autologous tissue-engineered aortic valves without using viruses or first reprogramming the cells into pluripotent stem cells.

In situ tissue engineering heart valves (TEHVs) are the most promising way to overcome the defects of existing valve prostheses. Despite their promising prospects, the clinical translation of TEHVs remains a formidable challenge, mainly due to unpredictable host interactions post-implantation. An immunomodulatory idea based on hydrogel encapsulation of nanoparticle-coated heart valve scaffolds is introduced. Specifically, galactose-modified human serum albumin nanoparticles (miR-93@HSA NPs) to deliver microRNA-93 mimics are utilized, which target macrophages and induce their differentiation into the anti-inflammatory M2 subtype, fostering a conducive immune microenvironment. Matrix metalloproteinase (MMP)-responsive hydrogel is used to encapsulate the nanoparticles, enabling targeted and sustained release. Results show that the miR-93@HSA NPs exhibit excellent ability to induce macrophage polarization toward the M2 phenotype. A decellularized valve modified with hydrogel reveals MMP-response release of the miR-93@HSA NPs. In vitro, the immunomodulatory heart valve possesses good endocytocompatibility and effectively reprograms macrophages when cocultured with HUVECs or RAW264.7 macrophages. In vivo, this valve scaffold promises to mitigate early inflammatory damage and provide a pro-endothelialization niche for scaffolds' constructive remodeling. With the use of cell coculture systems and transcriptome sequencing, the mechanism of immune-modulating scaffold accelerating endothelialization is being elucidated. The immunomodulatory heart valve scaffold holds promising potential for clinical translation.

Xenogeneic decellularized heart valves (DHVs) have become one of the most commonly used scaffolds for tissue engineered heart valves (TEHVs) due to extensive resources and possessing the distinct three-layer structure similar to native heart valves. However, DHVs as scaffolds face the shortages such as poor mechanical properties, proneness to thrombosis and calcification, difficulty in endothelialization and chronic inflammatory responses etc., which limit their applications in clinic. In this work, we constructed a novel TEHV with immunomodulatory functions by loading folic acid modified silver nanoparticles (FS NPs) on DHVs to overcome these issues. The FS NPs preferentially targeted M1 macrophages and reduced their intracellular H2O2 level, resulting in polarizing them into M2 phenotype. The increased M2 macrophages facilitated to eliminate inflammation, recruit endothelial cells, and promote their proliferation and endothelialization by secreting relative factors. We founded that FS NPs with the size of 80 nm modified DHVs (FSD-80) performed optimally on cytocompatibility and regulating macrophage phenotype ability in vitro. In addition, the FSD-80 had excellent mechanical properties, hemocompatibility and anti-bacteria property. The results of the subcutaneous implantation in rats revealed that the FSD-80 also had good performance in regulating macrophage phenotype, promoting endothelialization, remolding the extracellular matrix and anti-calcification in vivo. Therefore, FS NPs-loaded DHVs possess immunomodulatory functions, which is a feasible and promising strategy for constructing TEHVs with excellent comprehensive performance.

Tissue engineering heart valves (TEHVs) are expected to address the limitations of mechanical and bioprosthetic valves used in clinical practice. Decellularized heart valve (DHV) is an important scaffold of TEHVs due to its natural three-dimensional structure and bioactive extracellular matrix, but its mechanical properties and hemocompatibility are impaired. In this study, DHV is cross-linked with three different molecular weights of oxidized hyaluronic acid (OHA) by a Schiff base reaction and presented enhanced stability and hemocompatibility, which could be mediated by the molecular weight of OHA. Notably, DHV cross-linked with middle- and high-molecular-weight OHA could drive the macrophage polarization toward the M2 phenotype in vitro. Moreover, DHV cross-linked with middle-molecular-weight OHA scaffolds are further modified with RGD-PHSRN peptide (RPF-OHA/DHV) to block the residual aldehyde groups of the unreacted OHA. The results show that RPF-OHA/DHV not only exhibits anti-calcification properties, but also facilitates endothelial cell adhesion and proliferation in vitro. Furthermore, RPF-OHA/DHV shows excellent performance under an in vivo hemodynamic environment with favorable recellularization and immune regulation without calcification. The optimistic results demonstrate that OHA with different molecular weights has different cross-linking effects on DHV and that RPF-OHA/DHV scaffold with enhanced immune regulation, anti-calcification, and recellularization properties for clinical transformation.

Valve replacement is the most effective means of treating heart valve diseases, and transcatheter heart valve replacement (THVR) is the hottest field at present. However, the durability of the commercial bioprosthetic valves has always been the limiting factor restricting the development of interventional valve technology. The chronic inflammatory reaction, calcification, and difficulty in endothelialization after the implantation of a glutaraldehyde cross-linked porcine aortic valve or bovine pericardium often led to valve degeneration. Improving the biocompatibility of valve materials and inducing endothelialization to promote in situ regeneration can extend the service life of valve materials. Herein, inspired by the hardening process of butterfly wings, this study proposed a dopamine-metal-phenol strategy to modify decellularized porcine pericardium (DPP). This is a strategy to make dopamine (DA) coordinate trivalent metal chromium ions (Cr(III)) with antiplatelets (PLTs) and anti-inflammatory properties, and then cross-link it with tea polyphenols (TP) to generate a valve scaffold that is mechanically comparable to glutaraldehyde-cross-linked scaffolds but avoids the cytotoxicity of aldehyde and presents better biocompatibility, hemocompatibility, anticalcification, and anti-inflammatory response properties.

The beneficial effects of physical exercise on human cardiorespiratory fitness might be through reduced systemic inflammation, but the mechanism remains a controversy. Recent studies have highlighted the importance of spleen microbiomes in immune regulation. Hence, we conducted a study using a high-fat diet and exercise mouse model to investigate the relationships among different exercise intensities, spleen microbiome composition, and cardiac function. The mice spleen contained a diverse array of microbiota. Different intensities of exercise resulted in varying compositions of the spleen microbiome, Treg cell levels, and mouse heart function. Additionally, the abundance of Lactobacillus johnsonii in the mouse spleen exhibited a positive correlation with Treg cell levels, suggesting that Lactobacillus johnsonii may contribute to the production of Treg cells, potentially explaining the protective role of moderate-intensity exercise on cardiac function. In conclusion, our findings provide evidence that moderate-intensity exercise may promote cardiac function protection by influencing the spleen microbiome composition.

Tissue engineering heart valve (TEHV) offers great potential to overcome the limitations of commercial artificial valves used in clinical practice as a permanent prosthetic valve. Currently, decellularized heart valve (DHV) is the most widely used scaffold for TEHV, but showed suboptimal performance due to difficulty of endothelialization. Facilitating endothelialization of DHV is indispensable for better valve performance, and excellent hemocompatibility guarantees enough time windows for endothelialization process. Herein, a dual-functional TEHV scaffold with improving hemocompatibility and accelerating endothelialization is constructed by modifying DHV with copper ions (Cu) and growth differentiation factor 11 (GDF11). Results show the newly-constructed scaffold successfully generates endogenous nitric oxide (NO) through catalysis of Cu, and possesses improved hemocompatibility by down-regulating platelets activation and adhesion. Furthermore, GDF11 immobilization significantly accelerates scaffold endothelialization through facilitating recruitment, supporting growth, and alleviating apoptosis of endothelial progenitor cells . This TEHV scaffold shows favorable performance under in vivo hemodynamic environment with intact endothelial coverage and adaptive ECM remodeling, and without thrombus or calcification formation. This newly-constructed TEHV scaffold is expected to make up for the shortcomings of currently available prosthetic valves in clinical practice and has the potential possibility of rapid translation to the clinic as a better prosthetic valve.

Background: Abdominal aortic aneurysms (AAA) are chronic inflammation in nature and are closely related to macrophages. The purpose was to explore regulating macrophage polarization with target-macrophage nanoparticles impacting the development of AAA.Methods: Galactose-modified nanoparticles were prepared by self-assembly technology for delivering microRNA (miR)-223. In AngiotensinII-induced experimental AAA model, miR-223-loaded nanoparticles (MirNPs) or PBS was injected at day 7 before and after operation, respectively. Cultured cells and aortic specimen were collected to be analyzed with histology and biochemical examination.Results: In vitro, miR-223 promoted bone marrow-derived macrophages (BMDMs) to polarize to M2. In experimental AAA model, MirNPs significantly decreased the AAA incidence and the ratio of M1 macrophages and production of related proinflammatory cytokines. Furthermore, MirNPs also reduced the expression of the NLRP3 inflammasome.Conclusion: Our findings suggested that miR-223-loaded nanoparticles targeting macrophage polarization may mitigate AAA progression via downregulating of NLRP3.(c) 2022 Published by Elsevier Inc.

Objective To investigate changes in peripheral erythrocyte methylmercury among pregnant women during different gestational periods and the methylmercury in neonatal umbilical cord blood erythrocyte. MethodsTotally 79 pregnant women having prenatal examination were recruited at a women′s and children′s health care center in Wuhan city during January – April, 2019. The women′s peripheral blood samples were collected at the first trimester (12 ± 2 weeks of gestation) and the third trimester (37 ± 2 weeks of gestation) and neonatal umbilical cord blood samples were also collected. Red blood cells of the samples were separated and concentrations of methylmercury in the cells were detected with high performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICP-MS). Results The geometric means of erythrocyte methylmercury of all the women were 0.322 μg/g (interquartile range [IRQ]: 0.188 – 0.728 μg/g) for the samples of first trimester, 0.238 μg/g (IRQ: 0.120 – 0.549 μg/g ) for those of third trimester, and 0.515 μg/g (IRQ: 0.322 – 1.099 μg/g) for neonatal umbilical cord samples. The erythrocyte methylmercury of the first trimester samples was significantly higher than that of the third trimester samples (P < 0.05); while, the erythrocyte methylmercury of both the first trimester and the third trimester samples were significantly lower than that of neonatal umbilical cord samples (both P < 0.05). The erythrocyte methylmercury of the umbilical cord blood samples, the first trimester samples and the third trimester samples were closely correlated with each other, with the correlation coefficients of 0.763, 0.866, and 0.854, respectively. Conclusion The erythrocyte methylmercury of pregnant women during first and third trimester and that of neonatal umbilical cord blood are significantly correlated with each other. Higher erythrocyte methylmercury of neonatal umbilical cord blood than that of women during pregnancy suggests a possible enrichment of methyl mercury.

Coronavirus disease 2019 (COVID-19) has caused a global pandemic impacting over 200 countries/regions and more than 200 million patients worldwide. Among the infected patients, there is a high prevalence of COVID-19-related cardiovascular injuries. However, the specific mechanisms linking cardiovascular damage and COVID-19 remain unclear. The COVID-19 pandemic also has exacerbated the mental health burden of humans. Considering the close association between neuroimmune interactions and cardiovascular disease, this review assessed the complex pathophysiological mechanisms connecting neuroimmune interactions and cardiovascular disease. It was revealed that the mental health burden might be a pivotal accomplice causing COVID-19-associated cardiovascular damage. Specifically, the proinflammatory status of patients with a terrible mood state is closely related to overdrive of the hypothalamus-pituitary-adrenal (HPA) axis, sympathovagal imbalance, and endothelial dysfunction, which lead to an increased risk of developing cardiovascular injury during COVID-19. Therefore, during the prevention and treatment of cardiovascular complications in COVID-19 patients, particular attention should be given to relieve the mental health burden of these patients.

Background: Thoracic aortic aneurysm and dissection (TAAD) is caused by the apoptosis and phenotypic trans-formation of vascular smooth muscle cells (VSMCs). The dysfunction of VSMCs affects their secretion of che-mokines such as monocyte chemoattractant protein-1 (MCP-1) to recruit the infiltration of macrophages which release proinflammatory cytokines and matrix metalloproteinases (MMPs) to accelerate the process of TAAD formation. Approach and results: We analyzed the expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) in aortic tissues of TAAD patients and the beta-aminopropionitrile fumarate (BAPN)-induced mouse model, and the levels of Nrf2 were elevated in both aortic lesions. Treatment with the Nrf2 activator oltipraz protects against the formation of BAPN-induced aneurysm and dissection, as demonstrated by a higher survival rate, postponing the time of aortic rupture, and inhibiting aortic luminal dilation. In addition, the thoracic aortas of BAPN-treated mice inhibited the apoptosis and phenotypic transformation of VSMCs. When treated with oltipraz, they had reduced macrophage infiltration proinflammatory cytokines and MMPs. Furthermore, oltipraz treatment pro-moted the translocation of Nrf2 and downregulated the NLRP3 pathway. Conclusion: Nrf2 plays a crucial role in protecting against TAAD development, and persistent activation of Nrf2 is a promising therapeutic strategy against the progression of TAAD.

Purpose: This study detects SARS-CoV-2 in the ocular surface through one-step reverse transcription droplet digital PCR (one-step RT-ddPCR) and evaluates the possibility of the ocular surface as a possible transmission route. Methods: A single-center prospective observational study was designed to investigate the viral loads in ocular surface. Specimens including the conjunctival swabs, nasopharyngeal swabs and blood were synchronously collected at a single time point for all COVID-19 patients. SARS-CoV-2 loads in nasopharyngeal swabs were tested by real-time polymerase chain reaction (PCR); the blood samples and conjunctival swabs were tested by real-time PCR and one-step RT-ddPCR. Results: Sixty-eight COVID-19 patients confirmed by nasopharyngeal real-time PCR were recruited. In the single time point test, 40 cases showed positive SARS-CoV-2 detection in either the blood, tears, or nasopharynx, of which four cases were triple-positive, 10 were dual-positive, and 26 were single-positive. The positive rate of nasopharyngeal swab realtime PCR test was 22.1% (15/68). The positive rate of blood and conjunctival swabs by onestep RT-ddPCR was 38.2% (26/68) and 25% (17/68), respectively, whereas real-time PCR was all negative. Positive conjunctival swabs were significantly correlated with positive nasopharyngeal swabs (P = 0.028). The sampling lags from illness onset to sampling day in 3 out of 4 triple-positive patients and in 9 out of 10 dual-positive patients were respectively less than 9 days and less than 20 days. Conclusion: Our results indicate that the positive rate of SARS-CoV-2 on the ocular surface is much higher than expected. Transmission possibility through the ocular surface may be greatly underestimated.