Synergetic sludge conditioning by US enhanced Fe2+ activated sodium persulfate: physicochemical properties and mechanisms.

Efficient dewatering of sewage sludge is an energy- and carbon-saving procedure for sludge treatment in wastewater treatment facilities. The ultrasound-coupled divalent iron ion activated persulfate process can effectively promote sludge dewatering and improve organic substance content. Under the action of ultrasound (US 50 w/L), divalent iron ions (Fe2+) 200 mg/g (TS), and persulfate (PDS) 200 mg/g (TS) for 60 min, the capillary suction time (CST) was reduced by 79.74%, and the moisture content of the dewatered sludge cake reached 56.51 wt%. The organic carbon content of treated sludge was also four times higher than the original sludge and types were richer in short-chain volatile species in US/Fe2+/PDS. Moreover, the correlation analysis found that the relationship of between CST and SV30, Zeta and lactate dehydrogenase (LDH) were positive correlation, and the relationship of SCOD and TC were positively correlated with the PN (SB-EPS). Mechanistic studies showed that the US/Fe2+/PDS system could produce oxygen activators by US coupling Fe2+ to strengthen the effect of activated PDS strongly, while the sulfate radicals (SO4·-) radical was a dominant role. The cracking mechanism is divided into two pathways effectively degraded the macromolecule EPS into a small-molecule acid and further reduced the water-holding interfacial affinity as follow: (1) the radical path dominated by hydroxyl radicals (·OH), SO4·-, and superoxide radical (O2·-); (2) the non-radicals dominated by monoclinic oxygen (1O2). Afterwards, the electrostatic force and interfacial free energy were reduced, resulting in enhanced self-flocculation and mobility to enhanced dewaterability. These findings demonstrated the US/Fe2+/PDS system had significant advantages in sludge cracking and provided theoretical support for its practical application.

An Integrated Arterial Remodeling Hydrogel for Preventing Restenosis After Angioplasty.

The high incidence of restenosis after angioplasty has been the leading reason for the recurrence of coronary heart disease, substantially increasing the mortality risk for patients. However, current anti-stenosis drug-eluting stents face challenges due to their limited functions and long-term safety concerns, significantly compromising their therapeutic effect. Herein, a stent-free anti-stenosis drug coating (denoted as Cur-NO-Gel) based on a peptide hydrogel is proposed. This hydrogel is formed by assembling a nitric oxide (NO) donor-peptide conjugate as a hydrogelator and encapsulating curcumin (Cur) during the assembly process. Cur-NO-Gel has the capability to release NO upon ß-galactosidase stimulation and gradually release Cur through hydrogel hydrolysis. The in vitro experiments confirmed that Cur-NO-Gel protects vascular endothelial cells against oxidative stress injury, inhibits cellular activation of vascular smooth muscle cells, and suppresses adventitial fibroblasts. Moreover, periadventitial administration of Cur-NO-Gel in the angioplasty model demonstrate its ability to inhibit vascular stenosis by promoting reendothelialization, suppressing neointima hyperplasia, and preventing constrictive remodeling. Therefore, the study provides proof of concept for designing a new generation of clinical drugs in angioplasty.

Pericardial Delivery of SDF-1α Puerarin Hydrogel Promotes Heart Repair and Electrical Coupling.

The stromal-derived factor 1α/chemokine receptor 4 (SDF-1α/CXCR4) axis contributes to myocardial protection after myocardial infarction (MI) by recruiting endogenous stem cells into the ischemic tissue. However, excessive inflammatory macrophages are also recruited simultaneously, aggravating myocardial damage. More seriously, the increased inflammation contributes to abnormal cardiomyocyte electrical coupling, leading to inhomogeneities in ventricular conduction and retarded conduction velocity. It is highly desirable to selectively recruit the stem cells but block the inflammation. In this work, SDF-1α-encapsulated Puerarin (PUE) hydrogel (SDF-1α@PUE) is capable of enhancing endogenous stem cell homing and simultaneously polarizing the recruited monocyte/macrophages into a repairing phenotype. Flow cytometry analysis of the treated heart tissue shows that endogenous bone marrow mesenchymal stem cells, hemopoietic stem cells, and immune cells are recruited while SDF-1α@PUE efficiently polarizes the recruited monocytes/macrophages into the M2 type. These macrophages influence the preservation of connexin 43 (Cx43) expression which modulates intercellular coupling and improves electrical conduction. Furthermore, by taking advantage of the improved "soil", the recruited stem cells mediate an improved cardiac function by preventing deterioration, promoting neovascular architecture, and reducing infarct size. These findings demonstrate a promising therapeutic platform for MI that not only facilitates heart regeneration but also reduces the risk of cardiac arrhythmias.

Lactobacillus rhamnosus GG aggravates vascular calcification in chronic kidney disease: A potential role for extracellular vesicles.

AIMS: Lactobacillus rhamnosus GG (LGG) is a probiotic with great promise in future clinical application, which can significantly promote bone formation. However, the effect of LGG on CKD-related vascular calcification is unclear. In this study, we aimed to investigate the effect of LGG on CKD-related vascular calcification. MATERIALS AND METHODS: After 2 weeks of 5/6 nephrectomy, CKD rats received a special diet (4 % calcium and 1.8 % phosphate) combined with 1,25-dihydroxyvitamin D3 to induce vascular calcification. Meanwhile, CKD rats in the LGG group were gavaged orally with LGG (1 × 109 CFU bacteria/day). 16S RNA amplicon sequencing was performed to analyze the effect of LGG treatment on gut microbiota composition. Furthermore, differential ultracentrifugation was utilized to extract EVs. The effects of EVs on vascular calcification were evaluated in rat VSMCs, rat aortic rings, and CKD rat calcification models. In this study, vascular calcification was assessed by microcomputed tomography analysis, alizarin red staining, calcium content determination, and the expression of osteogenic transcription factors RUNX2 and BMP2. KEY FINDINGS: LGG remarkably aggravated vascular calcification. LGG supplementation significantly altered gut microbiota composition in CKD rats, particularly increasing Lactobacillus. Interestingly, EVs presented a significant promoting effect on the development of calcification. Finally, mechanistic analysis proved that EVs aggravated vascular calcification through PI3K/AKT signaling. SIGNIFICANCE: These results do not support the supplementation of LGG in CKD-associated vascular calcification patients. Our study presented a fresh perspective on LGG with potential risks and adverse effects. CKD patients should use specific probiotic strains cautiously.

Targeted heart repair by Tß4-loaded cardiac-resident macrophage-derived extracellular vesicles modified with monocyte membranes.

Recent studies have demonstrated the critical role of cardiac-resident macrophages (cMacs) in the maintenance of physiological homeostasis. However, recruitment of circulating monocyte-derived macrophages decreases cMac levels post-myocardial infarction (MI). Transplanting cMacs is not an ideal option due to their low survival rates and the risk of immunological rejection. However, extracellular vesicle therapy has the potential to provide a feasible and safe alternative for cardiac repair. In this study, cell membrane-modified extracellular vesicles (MmEVs) were developed for heart repair by modifying cMac-derived extracellular vesicles (mEVs) with monocyte membranes, resulting in immune evasion and sequential targeted localization to damaged regions through expression of CD47 on MmEVs and strong affinity between monocyte membrane proteins and CCL2. Additionally, to fully exploit the potential clinical application of MmEVs and achieve a better curative effect, thymosin ß4 (Tß4) was loaded into the nanoparticles, resulting in Tß4-MmEVs. In vitro experiments indicated that both the MmEVs and Tß4-MmEVs promoted cardiomyocyte proliferation and endothelial cell migration. Animal experiments suggested that MI mice treated with MmEVs and Tß4-MmEVs exhibited reduced myocardial fibrosis and increased vascular density compared to the control group. Thus, we posit that these targeted nanoparticles hold significant potential for MI adjuvant therapy and may open new avenues for cardiac repair and regeneration. STATEMENT OF SIGNIFICANCE: Extracellular vesicles (EVs) derived from bioactive parent cell sources involved in pathological and repair processes for cardiovascular disease have emerged as a compelling strategy for regenerative therapy. In this study, we constructed monocyte membrane-modified extracellular vesicles loaded with a drug (Tß4-MmEVs) for heart repair that exhibit extraordinary abilities of immune evasion and sequential localization to damaged regions owing to the presence of CD47 and the strong affinity between monocytes and damaged cardiomyocytes and endothelial cells. The bioactivities of Tß4-MmEVs on enhancing cardiomyocyte and endothelial cell proliferation were validated both in vitro and in vivo. Effective development and implementation of therapeutically membrane-modified nanoparticles from homologous origins can provide a reference for adjuvant therapy in clinical MI management.

Long-Term Cardiovascular Mortality among 80,042 Older Patients with Bladder Cancer.

BACKGROUND: To identify the risk of death from cardiovascular disease (CVD) in older patients with bladder cancer (BC). METHODS: This population-based study included 80,042 older BC patients (≥65 years) diagnosed between 1975 and 2018, with a mean follow-up of 17.2 years. The proportion of deaths, competing risk models, standardized mortality ratio (SMR), and absolute excess risk (AER) per 10,000 person-years were applied to identify the risk of CVD-related deaths among older BC patients. RESULTS: For older patients with BC, CVD-related death was the chief cause of death, and cumulative CVD-related mortality also exceeded primary BC as the leading cause of death mostly 5-10 years after BC diagnosis, especially in localized-stage and low-grade subgroups. The risk of short- and long-term CVD-related death in older BC patients was higher than in the general older adult population (SMR = 1.30, 95% CI 1.28-1.32; AER = 105.68). The risk of sex-specific CVD-related deaths also increased compared to the general population of older adults, including heart disease, cerebrovascular diseases, hypertension without heart disease, atherosclerosis, aortic aneurysm and dissection, and other diseases of the arteries, arterioles, and capillaries. CONCLUSIONS: CVD-related death is an important competing risk among older BC patients and has surpassed primary BC as the chief cause of death, mainly 5-10 years after BC diagnosis. The risk of CVD-related death in older patients with BC was greater than in the general population. The management of older patients with BC should focus not only on the primary cancer but also on CVD-related death.

Construction of a Band-Aid Like Cardiac Patch for Myocardial Infarction with Controllable H2 S Release.

Excessive or persistent inflammation incites cardiomyocytes necrosis by generating reactive oxygen species in myocardial infarction (MI). Hydrogen sulfide (H2 S), a gaseous signal molecule, can quickly permeate cells and tissues, growing concerned for its cardioprotective effects. However, short resident time and strong side effects greatly restrict its application. Herein, a complex scaffold (AAB) is first developed to slowly release H2 S for myocardial protection by integrating alginate modified with 2-aminopyridine-5-thiocarboxamide (H2 S donor) into albumin electrospun fibers. Next, a band-aid like patch is constructed based on AAB (center) and nanocomposite scaffold which comprises albumin scaffold and black phosphorus nanosheets (BPNSs). With near-infrared laser (808 nm), thermal energy generated by BPNSs can locally change the molecular structure of fibrous scaffold, thereby attaching patch to the myocardium. In this study, it is also demonstrated that AAB can enhance regenerative M2 macrophage and attenuate inflammatory polarization of macrophages via reduction in intracellular ROS. Eventually, this engineered cardiac patch can relieve inflammation and promote angiogenesis after MI, and thereby recover heart function, providing a promising therapeutic strategy for MI treatment.

Fabrication of Tß4-Exosome-releasing artificial stem cells for myocardial infarction therapy by improving coronary collateralization.

Currently, stem cell transplantations in cardiac repair are limited owing to disadvantages, such as immunological rejection and poor cell viability. Although direct injection of exosomes can have a curative effect similar to that of stem cell transplantation, high clearance hinders its application in clinical practice. Previous reports suggested that induction of coronary collateralization can be a desired method of adjunctive therapy for someone who had missed the optimal operation time to attenuate myocardial ischemia. In this study, to mimic the paracrine and biological activity of stem cells, we developed artificial stem cells that can continuously release Tß4-exosomes (Tß4-ASCs) by encapsulating specific exosomes within microspheres using microfluidics technology. The results show that Tß4-ASCs can greatly promote coronary collateralization in the periphery of the myocardial infarcted area, and its therapeutic effect is superior to that of directly injecting the exosomes. In addition, to better understand how it works, we demonstrated that the Tß4-ASC-derived exosomes can enhance the angiogenic capacity of coronary endothelial cells (CAECs) via the miR-17-5p/PHD3/Hif-1α pathway. In brief, as artificial stem cells, Tß4-ASCs can constantly release functional exosomes and stimulate the formation of collateral circulation after myocardial infarction, providing a feasible and alternative method for clinical revascularization.