UGCG modulates heart hypertrophy through B4GalT5-mediated mitochondrial oxidative stress and the ERK signaling pathway.

Mechanical pressure overload and other stimuli often contribute to heart hypertrophy, a significant factor in the induction of heart failure. The UDP-glucose ceramide glycosyltransferase (UGCG) enzyme plays a crucial role in the metabolism of sphingolipids through the production of glucosylceramide. However, its role in heart hypertrophy remains unknown. In this study, UGCG was induced in response to pressure overload in vivo and phenylephrine stimulation in vitro. Additionally, UGCG downregulation ameliorated cardiomyocyte hypertrophy, improved cardiomyocyte mitochondrial oxidative stress, and reduced the ERK signaling pathway. Conversely, UGCG overexpression in cardiomyocytes promoted heart hypertrophy development, aggravated mitochondrial oxidative stress, and stimulated ERK signaling. Furthermore, the interaction between beta-1,4-galactosyltransferase 5 (B4GalT5), which catalyses the synthesis of lactosylceramide, and UGCG was identified, which also functions as a synergistic molecule of UGCG. Notably, limiting the expression of B4GalT5 impaired the capacity of UGCG to promote myocardial hypertrophy, suggesting that B4GalT5 acts as an intermediary for UGCG. Overall, this study highlights the potential of UGCG as a modulator of heart hypertrophy, rendering it a potential target for combating heart hypertrophy.

Nonatheromatous Popliteal Artery Disease.

OBJECTIVE: Peripheral artery disease (PAD) is often caused by atherosclerosis. However, causes other than atherosclerosis is often overlooked. Popliteal artery entrapment syndrome (PAES) and popliteal artery adventitial cystic disease (PACD) are two common nonatheromatous causes of claudication and critical limb ischemia. The purpose of this study is to present early results of treatment of PAES and PACD involving the lower limbs. METHODS: From December 2019 to February 2021, 10 patients with PAES underwent surgeries, and 1 patient with PAES received conservative treatment. 2 patients with PACD underwent surgery. Patient data including age, gender, etiology of vascular pathology, diseased vessel, surgical method, and hemodynamic status were collected retrospectively. RESULTS: The mean follow-up duration was 5.64 ± 3.72 months (range, 1-12 months). All patients had their symptoms improved or resolved. The success rate of surgery was 100%, the rate of freedom from reintervention for any reason was 100%. There were no death, bleeding, embolism, or skin ulcers during late follow-up. CONCLUSIONS: PAES and PACD require early diagnosis and intervention, and early surgery may lead to good early- and mid-term results.

A Systematic Review and Meta-Analysis of Seasonal and Monthly Variability in the Incidence of Acute Aortic Dissection.

BACKGROUND: This study explored seasonal and monthly variations of the incidence of acute aortic dissection (AAD). METHODS: MEDLINE, EMBASE, and the Cochrane Library databases were searched up to July 2021. Temporal variation in the incidence of AAD was analyzed including all studies analyzing seasonal and monthly aggregations. Then, we performed subgroup analyses according to the type of AAD. Two authors independently reviewed and extracted data. RESULTS: Twenty-seven studies for a total of 128,101 patients were included. Our results showed that the incidence of AAD was highest in winter and lowest in summer. Regardless of type A or type B, the incidence of AAD was significantly higher in winter than in summer and autumn. Nonetheless, there was no significant difference between spring and winter, and between summer and autumn. Results may be limited by the quality of the included articles. However, in the sensitivity analysis that excluded low-quality studies, results did not change significantly. In addition, the pooled incidence was highest in January and lowest in August. CONCLUSIONS: Our data strongly support the presence of distribution patterns in the incidence of AAD, characterized by significantly higher risk in winter and in January. These distribution patterns of AAD incidence may help to develop better prevention strategies.

Early Outcomes of Complex Vascular Reconstructions in Lower Extremities Using Spiral and Panel Vein Grafts.

BACKGROUND: Spiral saphenous vein grafts (SSVG) or paneled vein grafts (PVG) can be used when the diameter of the autologous great saphenous vein does not match the vessel that needs to be repaired. This study aimed to present early results of complex vascular reconstruction with SSVGs and PVGs in the lower extremities. METHODS: From May 2019 through January 2021, 6 SSVGs and 3 PVGs were used for vascular reconstruction in 9 patients. Patient data were collected retrospectively, including age, gender, cause of vascular pathology, target vessels, concomitant injury, surgical method, additional surgical methods, and hemodynamic status. The Kaplan-Meier method was used to calculate the rate of freedom from reintervention. RESULTS: Among these patients, 7 had trauma, 1 had graft infection, and 1 had vascular reconstruction after tumor excision. The mean duration of follow-up was 6 ± 6.6 months (range 1-19 months). The rate of freedom from reintervention for any reason was 77.8% at 1 year. Two patients underwent amputation after vascular reconstruction with patent vascular reconstructions. One of the 2 amputations was performed because of infection, and the other was due to ischemia >24 hr. The success rate of reconstruction was 100%, and the primary patency rate was 100%. The rate of limb salvage was 77.8%. There was no death, bleeding, embolism, skin ulcers, graft-related complication, or aneurysmal dilation during follow-up. CONCLUSIONS: SSVG and PVG were associated with low infection rates and satisfactory short-term patency rates. Both 2 grafts may be good choices when there is a diameter mismatch in vascular reconstructions.

New phosphate-based binder for stabilization of soils contaminated with heavy metals: leaching, strength and microstructure characterization.

Cement stabilization is used extensively to remediate soils contaminated with heavy metals. However, previous studies suggest that the elevated zinc (Zn) and lead (Pb) concentrations in the contaminated soils would substantially retard the cement hydration, leading to the deterioration of the performance of cement stabilized soils. This study presents a new binder, KMP, composed of oxalic acid-activated phosphate rock, monopotassium phosphate and reactive magnesia. The effectiveness of stabilization using this binder is investigated on soils spiked with Zn and Pb, individually and together. Several series of tests are conducted including toxicity characteristic leaching (TCLP), ecotoxicity in terms of luminescent bacteria test and unconfined compressive strength. The leachability of a field Zn- and Pb- contaminated soil stabilized with KMP is also evaluated by TCLP leaching test. The results show that the leached Zn concentrations are lower than the China MEP regulatory limit except when Zn and Pb coexist and for the curing time of 7 days. On the other hand, the leached Pb concentrations for stabilized soils with Pb alone or mixed Zn and Pb contamination are much lower than the China MEP or USEPA regulatory limit, irrespective of the curing time. The luminescent bacteria test results show that the toxicity of the stabilized soils has been reduced considerably and is classified as slightly toxic class. The unconfined compressive strength of the soils decrease with the increase in the Zn concentration. The stabilized soils with mixed Zn and Pb contaminants exhibit notably higher leached Zn concentration, while there is lower unconfined compressive strength relative to the soils when contaminated with Zn alone. The X-ray diffraction and scanning electron microscope analyses reveal the presence of bobierrite (Mg3(PO4)2·8H2O) and K-struvite (MgKPO4·6H2O) as the main products formed in the KMP stabilized uncontaminated soils; the formation of hopeite (Zn3(PO4)2·4H2O), scholzite (CaZn2(PO4)2·2H2O), zinc hydroxide (Zn(OH)2), and fluoropyromorphite (Pb5(PO4)3F) in the soils are the main mechanisms for immobilization of Zn and Pb with the KMP binder. The change in the relative quantities of the formed phosphate-based products, with respect to the Zn concentration and presence of mixed Zn and Pb contaminants, can well explain the measured impact of the Zn concentration levels and presence of both Zn and Pb contaminants on the unconfined compressive strength of the KMP stabilized soils.

Gut microbial co-metabolite 2-methylbutyrylcarnitine exacerbates thrombosis via binding to and activating integrin α2ß1.

Thrombosis represents the leading cause of death and disability upon major adverse cardiovascular events (MACEs). Numerous pathological conditions such as COVID-19 and metabolic disorders can lead to a heightened thrombotic risk; however, the underlying mechanisms remain poorly understood. Our study illustrates that 2-methylbutyrylcarnitine (2MBC), a branched-chain acylcarnitine, is accumulated in patients with COVID-19 and in patients with MACEs. 2MBC enhances platelet hyperreactivity and thrombus formation in mice. Mechanistically, 2MBC binds to integrin α2ß1 in platelets, potentiating cytosolic phospholipase A2 (cPLA2) activation and platelet hyperresponsiveness. Genetic depletion or pharmacological inhibition of integrin α2ß1 largely reverses the pro-thrombotic effects of 2MBC. Notably, 2MBC can be generated in a gut-microbiota-dependent manner, whereas the accumulation of plasma 2MBC and its thrombosis-aggravating effect are largely ameliorated following antibiotic-induced microbial depletion. Our study implicates 2MBC as a metabolite that links gut microbiota dysbiosis to elevated thrombotic risk, providing mechanistic insight and a potential therapeutic strategy for thrombosis.

Comprehensive Optimization of Western Blotting.

Western blotting is one of the most extensively used techniques in the biomedical field. However, it is criticized by many researchers due to its considerable time consumption, multiple steps, and low method results. Therefore, we modified the steps of gel preparation, electrophoresis, electrotransfer, blocking, and gel cutting. First, we simplified the gel preparation step by premixing various reagents and varying the amounts of catalysts or radical generators, which shortened the entire process to 10 min. Second, we shortened the electrophoresis process to 35 min by modifying the formula of the electrophoresis running buffer. Then, we removed the hazard of methanol vapor by replacing methanol with ethanol in the electrotransfer buffer. Finally, the use of polyvinylpyrrolidone-40 shortened the blocking procedure to 10 min. Our modifications shortened the time, improved the experimental productivity, and minimized the experimental cost without hindering compatibility with most existing equipment. The entire experiment up to primary antibody incubation can be completed within 80 min.

Fucoxanthin alleviated atherosclerosis by regulating PI3K/AKT and TLR4/NFκB mediated pyroptosis in endothelial cells.

Fucoxanthin, a type of natural xanthophyll carotenoid, is mainly present in seaweeds and various microalgae. This compound has been proved to possess multiple functions including antioxidation, anti-inflammation and anti-tumor. Atherosclerosis is widely deemed as a chronic inflammation disease, and as the basis of vascular obstructive disease. However, there is rare research about fucoxanthin's effects on atherosclerosis. In this study, we demonstrated that the plaque area of mice treated with fucoxanthin was significantly reduced compared to the group that did not receive fucoxanthin. In addition, Bioinformatics analysis showed that PI3K/AKT signaling might be involved in the protective effect of fucoxanthin, and this hypothesis was then verified in vitro endothelial cell experiments. Besides, our further results showed that endothelial cell mortality measured by TUNEL and flow cytometry was significantly increased in the oxidized low-density lipoprotein (ox-LDL) treatment group while significantly decreased in the fucoxanthin treatment group. In addition, the pyroptosis protein expression level in the fucoxanthin group was significantly lower than that in the ox-LDL group, which indicated that fucoxanthin improved the pyroptosis level of endothelial cells. Furthermore, it was revealed that TLR4/NFκB signaling were also participated in the protection of fucoxanthin on endothelial pyroptosis. Moreover, the protection of fucoxanthin on endothelial cell pyroptosis was abrogated when PI3K/AKT was inhibited or TLR4 was overexpressed, which further suggested the anti-pyroptosis effect of fucoxanthin was mediated through regulations of PI3K/AKT and TLR4/NFκB signaling.

Decellularized fish swim bladder patch loaded with mesenchymal stem cells inhibits neointimal hyperplasia.

We previously showed decellularized fish swim bladder can be used as vascular patch and tube graft in rats, mesenchymal stem cells (MSCs) have showed the capability to inhibit neointimal hyperplasia in different animal models. We hypothesized that decellularized fish swim bladder patch loaded with MSCs (bioinspired patch) can inhibit neointimal hyperplasia in a rat aortic patch angioplasty model. Rat MSCs were grown in vitro and flow cytometry was used to confirm their quality. 3.6 × 105 MSCs were mixed into 100 µl of sodium alginate (SA)/hyaluronic acid (HA) hydrogel, two layers of fish swim bladders (5 mm × 5 mm) were sutured together, bioinspired patch was created by injection of hydrogel with MSCs into the space between two layers of fish swim bladder patches. Decellularized rat thoracic aorta patch was used as control. Patches were harvested at days 1 and 14 after implantation. Samples were examined by histology, immunohistochemistry, and immunofluorescence. The decellularized rat thoracic aorta patch and the fish swim bladder patch had a similar healing process after implantation. The bioinspired patch had a similar structure like native aorta. Bioinspired patch showed a decreased neointimal thickness (p = .0053), fewer macrophages infiltration (p = .0090), and lower proliferation rate (p = .0291) compared to the double layers fish swim bladder patch group. Decellularized fish swim bladder patch loaded with MSCs can inhibit neointimal hyperplasia effectively. Although this is a preliminary animal study, it may have a potential application in large animals or clinical research.

Relationship between serum TGF- ß 1, MMP-9 and IL-1ß and pathological features and prognosis in breast cancer.

To investigate the levels of serum transforming growth factor-ß 1 (TGF-ß1), Matrix metalloproteinase-9 (MMP-9) and Interleukin-1 ß (IL-1 ß) in breast cancer (BC), and analyzing their relationship with pathological features and prognosis. Retrospective analysis of 86 subjects with BC (BC subgroup) and another 50 healthy subjects (control subgroup) during the same period were included. The clinical data were collected. In this research, in BC subgroup, The levels of serum TGF- ß 1, MMP-9 and IL-1 ß were significantly higher than those in control subgroup. The levels of TGF- ß 1 and MMP-9 in serum of BC subjects was correlated with clinical stage, histological grade, lymph node metastasis and molecular classification, but not with age, tumor size and menopausal status. The level of serum IL-1 ß was related to tumor size, clinical stage, histological grade and lymph node metastasis. Multivariate Logistic regression analysis showed that the high level of serum TGF- ß1 and MMP-9 was independent risk factors for BC. High level of serum IL-1 ß was not an independent risk factor for BC. The 3-year disease-free survival rate in high TGF- ß1 subgroup and high MMP-9 subgroup was significantly lower than that in low TGF- ß 1 subgroup and low MMP- 9 subgroup. To conclude, serum TGF- ß 1, MMP-9 and IL-1ß are highly expressed in BC, and the subjects with elevated serum levels of TGF- ß 1 and MMP-9 suggests poor prognosis.

Non-Surgical treatment Versus Surgery for Iatrogenic Femoral Artery Pseudoaneurysms: Systematic Review and Meta-Analysis.

Objectives: This study compared results of non-surgical treatment (compression and ultrasound guided thrombin injection (UGTI)) and surgery to treat iatrogenic femoral artery pseudoaneurysms. Methods: PubMed and Embase databases were searched up to October 2021. Primary outcome measure was success rate, and other outcomes examined were complication rate, reintervention rate. Two authors independently reviewed and extracted data. Data were presented as the odds ratios (ORs) with 95% confidence intervals (CIs). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to appraise the quality of the body of evidence. Results: Eight studies were included. A total of 623 patients with pseudoaneurysm undergoing treatment were included, of which 163 subjects underwent surgery, 397 subjects underwent compression, and 63 subjects underwent UGTI. The success rate was significantly lower in the non-surgery group (OR 0.24, 95% CI, 0.08-0.69, I 2 = 0%). The complication rate was significantly lower in the non-surgery group (OR 0.10, 95% CI, 0.03 -0.29, I 2 = 0%). Patients in the non-surgery group tended to have a lower, but statistically insignificant, reintervention rate (OR 0.11, 95% CI, 0.01-1.06, I 2 = 35%). Further, the GRADE assessment showed that these results (success rate, complication rate, and reintervention rate) were of very low quality. Conclusions: Available evidence shows that it is reasonable to regard non-surgical treatment as the primary treatment for iatrogenic femoral artery pseudoaneurysms, and surgery as a remedy after failure of non-surgical treatment in some cases.

Systematic Review and Meta-Analysis of Published Studies on Endovascular Repair of Abdominal Aortic Aneurysm With the p-Branch.

Background: Endovascular treatment of juxtarenal or pararenal abdominal aortic aneurysms is more popular than open surgery, mainly because it reduces perioperative mortality and morbidity. The custom-made fenestrated devices need to be tailored to each patient, so these devices require extra manufacturing and shipping time. The increased wait time may increase the risk of aneurysm rupture in some patients. In some situations, "Off-the-shelf" (OTS) fenestrated grafts can be used. The Cook Zenith p-Branch device (William Cook Australia, Brisbane, Australia) is a relatively common OTS. This study aimed to systematically evaluate all published experiences with p-Branch. Methods: We searched PubMed, Embase, and Cochrane to find works of literature that reported on the outcomes of patients treated with the p-Branch stent-grafts. Then we conducted an assessment of quality and meta-analysis of the results. The primary endpoints were the application rate of p-Branch stent-graft (type A, B), technical success rate, and early re-intervention rate. We estimated pooled proportions and 95% CIs. Results: Initial search of the literature included 111 articles, of which 7 studies were included in the end. A total of 260 patients were enrolled in these studies, and 218 patients were eventually treated with p-Branch. The pooled application rate of type A devices was 48% (95% CI, 29-67%), and pooled application rate of type B devices was 30% (95% CI, 16-44%). The pooled technical success rate was 87% (95% CI, 75-98%). The early re-intervention rate was 10% (95% CI, 3-17%). Midterm renal infarct rate (after 30 days) was 3% (95% CI, 0-6%). Midterm re-intervention rate (after 30 days) was 30% (95% CI, 3-57%). Midterm renal failure rate (after 30 days) was 6% (95% CI, 2-10%). Conclusions: This pooled analysis indicated an acceptable technical success rate after p-Branch stent-graft implantation, with early and midterm re-intervention rate and renal failure rate that cannot be ignored. The p-Branch repair of juxtarenal abdominal aortic aneurysms may be an appropriate and safe option, especially in emergency situations.

Outcomes of transcarotid artery revascularization: A systematic review.

BACKGROUND: Ischemic stroke and disability caused by carotid artery stenosis have always been worldwide problems. At present, carotid endarterectomy (CEA) and transfemoral carotid artery stenting (TFCAS) have been commonly used to treat carotid artery stenosis. Recently, transcarotid artery revascularization (TCAR) seems to be another option. METHODS: We searched PubMed and Embase to find literatures comparing TCAR with TFCAS and CEA. The primary outcomes were stroke, myocardial infarction (MI), transient ischemic attack (TIA), death, cranial nerve injure (CNI), and operative time. Secondary outcomes were stroke, death, MI in the elderly; cost; radiation; and entry site complication. RESULTS: Initial search of the literature included 165 articles, of which 12 studies were chosen in the end. These studies demonstrated high technical success rate of TCAR. Patients who received TCAR had lower risks of death, stroke/death and less radiation exposure compared to TFCAS. In meta analysis, the risk of stroke was significantly lower in TCAR group than TFCAS (OR 0.63; 95%CI 0.47-0.85). And there was no significant difference in TIA and MI. TCAR was associated with shorter operative time, lower risk of CNI and less blood loss compared to CEA. In older patients, the effect of TCAR was significantly better than that of TFCAS. CONCLUSION: TCAR is associated with a lower risk of perioperative stroke compared to TFCAS. TCAR is also associated with shorter operative time, lower risk of CNI and less blood loss compared to CEA. TCAR may be a promising treatment option besides TFCAS and CEA.

Egg Shell Membrane as an Alternative Vascular Patch for Arterial Angioplasty.

Introduction: The egg shell membrane (ESM) is always considered as waste, but recent studies have shown that it has the potential to yield rapid re-endothelialization in vitro. We hypothesized that ESM and heparin-conjugated ESM (HESM) can be used as arterial patch in a rat aortic angioplasty model. Method: Sprague-Dawley rat (200 g) abdominal aortic patch angioplasty model was used. Decellularized rat thoracic aorta (TA) patch was used as the control; ESM patch was made of raw chicken egg; heparin-coated ESM (HESM) patch was made by using dopamine; anticoagulation properties were verified using platelet adhesion tests; the TA, ESM, and HESM patches were implanted to the rat aorta and harvested at day 14; and the samples were examined by immunohistochemistry and immunofluorescence. Result: The ESM patch showed a similar healing process to the TA patch; the cells could migrate and infiltrate into both patches; there was a neointima with von Willebrand factor-positive endothelial cells; the endothelial cells acquired arterial identity with Ephrin-B2- and dll-4-positive cells; there were proliferating cell nuclear antigen (PCNA)-positive cells, and PCNA and alpha smooth muscle actin dual-positive cells in the neointima in both groups. Heparin was conjugated to the patch successfully and showed a strong anticoagulation property in vitro. HESM could decrease mural thrombus formation after rat aortic patch angioplasty. Conclusion: The ESM is a natural scaffold that can be used as a vascular patch; it showed a similar healing process to decellularized TA patch; HESM showed anticoagulation property both in vitro and in vivo; and the ESM may be a promising vascular graft in the clinic.

Delivery of rivaroxaban and chitosan rapamycin microparticle with dual antithrombosis and antiproliferation functions inhibits venous neointimal hyperplasia.

Neointimal hyperplasia is a complex process after vascular interventions, acute platelet deposition and smooth muscle cell proliferation both contributed to this process. There are still no perfect solutions to solve this problem. Rivaroxaban is a novel anticoagulant that has been widely used in clinic, it has a good pharmacological effects both in vivo and in vitro. Chitosan microparticle rapamycin (MP-rapa) was fabricated, interspaces of polyglycolic acid (PGA) scaffold were used as a reservoir of MP-rapa, and the scaffold was coated with hyaluronic acid rivaroxaban (MP-rapa-riva). Scanning electronic microscopy (SEM) photographs were taken and water contact angles were measured, rat inferior vena cava (IVC) patch venoplasty model was used; patches were harvested at day 14 and examined by immunohistochemistry and immunofluorescence. SEM photographs showed the microparticles rapamycin were inside the interspace of the scaffold, hyaluronic acid rivaroxaban was also successfully coated onto the surface of the scaffold. There was a thinner neointima, fewer proliferating cell nuclear antigen (PCNA) positive cells, fewer macrophages in the MP-rapa and MP-rapa-riva grafts compared to the control PGA graft. The result showed that this scaffold with dual anticoagulation and antiproliferation functions can effectively inhibit venous neointimal hyperplasia, although this is an animal experiment, it showed promising potential clinical application in the future.

ADAM17: A novel treatment target for aneurysms.

PURPOSE: The mechanisms underlying abdominal aortic aneurysms (AAAs) are still not fully understood, previous researches showed ADAM17 is increased in aneurysm. We hypothesized that inhibiting ADAM17 can decrease AAA formation and progression. MATERIALS AND METHODS: Aneurysm models were established in mouses and rats by aortic adventitial CaCl2 incubation and aortic pericardial patch angioplasty respectively. In mouse, control (no treatment) or SA/HA hydrogel loaded with TAPI-1 (ADAM17 inhibitor) were adventitial applied; in rat, control and TAPI-1 coated pericardial patch were used in rat aortic pericardial patch angioplasty. Samples were harvested on day 14 or 30 and analyzed by immunofluorescence. Bioinformatics analysis and immunostaining analysis were carried out to confirm the therapeutic potential of ADAM17 in the human AAA. RESULTS: ADAM17 was highly expressed in mouses, rats and human aneurysms. Adventitial application of SA/HA hydrogel loaded TAPI-1 or TAPI-1 conjugated pericardial patch can decrease AAA formation and progression in mouses and rats, respectively. Bioinformatic analysis showed ADAM17 promotes transformation of M1 macrophages and synthetic vascular smooth muscle cells, together with immunostaining analysis and results from animal models, the therapeutic potential of ADAM17 in the human AAA were confirmed. CONCLUSION: We showed that local delivery of ADAM17 inhibitor can inhibit aneurysm formation and progression in mouse and rat, these results showed ADAM17 plays an important role in the aneurysm formation and may be a potential treatment target.

PLGA Nanoparticle Rapamycin- or Necrostatin-1-Coated Sutures Inhibit Inflammatory Reactions after Arterial Closure in Rats.

Background: The inflammatory reaction of sutures and oozing after arterial closure depends on the suture material and the amount of oozing surrounding the sutures. Anti-inflammation coatings have been proven to be an effective strategy to decrease this reaction. The aim of this study was to establish an arterial closure oozing model in rats and to test the effect of poly (lactic-co-glycolic acid) (PLGA) nanoparticle (NP) rapamycin- or necrostatin-1(NEC-1)-coated sutures on the inflammatory reaction after arterial closure. Methods and Materials: A 10 mm arteriotomy was carried out on the carotid artery of Sprague-Dawley rats and closed using 11-0 sutures. PLGA NP-rapamycin and NEC-1 were made. The 11/0 nylon sutures were coated with PLGA NP-rapamycin and NEC-1. Sutures were examined by scanning electron microscopy, hemolysis test, and cumulative release. The carotid arteriotomy was closed using uncoated PLGA NP-rapamycin- and NP-NEC-1-coated sutures. The carotid artery was harvested on day 7. Tissues were examined by histology and immunohistochemistry. Results: There were severe inflammatory reactions in the oozing arteries compared to the normal healing arteries (P = 0.0192). PLGA NP-rapamycin- and NEC -1-coated sutures reduced foreign body reaction compared to the uncoated sutures. There were significantly smaller number of CD3 (P = 0.0068), CD45 (P = 0.0300), and CD68 (P = 0.0011) cells in the PLGA NP-rapamycin- and NP-NEC-1-coated groups compared to the uncoated group. There was a smaller number of p-mTOR (P = 0.0198)-positive cells in the PLGA NP-rapamycin-coated group compared to the uncoated group. There was a smaller number of TNFα (P = 0.0198)-positive cells in the PLGA NP-NEC-1-coated group compared to the uncoated group. Conclusions: In this rat carotid artery oozing model, PLGA NP-rapamycin- or NP-NEC-1-coated sutures can inhibit inflammatory reaction and foreign body reaction. Although this was a small rodent animal experiment, this coated suture may have a potential clinical application in the future.

Adventitial injection of HA/SA hydrogel loaded with PLGA rapamycin nanoparticle inhibits neointimal hyperplasia in a rat aortic wire injury model.

Neointimal hyperplasia is a persistent complication after vascular interventions, and it is also the leading cause of vascular graft restenosis and failure after arterial interventions, so novel treatment methods are needed to treat this complication. We hypothesized that adventitial injection of HA/SA hydrogel loaded with PLGA rapamycin nanoparticle (hydrogel-PLGA-rapamycin) could inhibit neointimal hyperplasia in a rat aortic wire injury model. The HA/SA hydrogel was fabricated by the interaction of hyaluronic acid (HA), sodium alginate (SA), and CaCO3; and loaded with PLGA rapamycin nanoparticle or rhodamine uniformly. A SD rat aortic wire injury induced neointimal hyperplasia model was developed, the control group only received wire injury, the adventitial application group received 10 µL hydrogel-PLGA-rapamycin after wire injury, and the adventitial injection group received 10 µL hydrogel-PLGA-rapamycin injected into the aortic adventitia after wire injury. Tissues were harvested at day 21 and analyzed by histology and immunohistochemical staining. Hydrogel loaded with rhodamine can be successfully injected into the aortic adventitia and was encapsuled by the adventitia. The hydrogel could be seen beneath the adventitia after adventitial injection but was almost degraded at day 21. There was a significantly thinner neointima in the adventitial application group and adventitial injection group compared to the control group (p = 0.0009). There were also significantly fewer CD68+ (macrophages) cells (p = 0.0012), CD3+ (lymphocytes) cells (p = 0.0011), p-mTOR+ cells (p = 0.0019), PCNA+ cells (p = 0.0028) in the adventitial application and adventitial injection groups compared to the control group. The endothelial cells expressed arterial identity markers (Ephrin-B2 and dll-4) in all these three groups. Adventitial injection of hydrogel-PLGA-rapamycin can effectively inhibit neointimal hyperplasia after rat aortic wire injury. This may be a promising drug delivery method and therapeutic choice to inhibit neointimal hyperplasia after vascular interventions.

The Current State of Vascular Surgery Presence in Bilibili Video Platform of China.

Background: With the development of the Internet, more and more patients search for disease-related information on video platforms during the treatment process, and physicians also look for learning materials through these video platforms. Bilibili is one of the most popular video platforms in China. This study evaluated information on various interesting topics, and related surgical procedures searched through Bilibili. Method: The Bilibili platform was independently queried for 12 common vascular diseases or related surgical procedures between October and November 2021 by two independent authors using the Baidu search engine. Information about the video and uploader was collected, and descriptive analyses of the overall and first-page results were performed. Results: A total of 3,998 search results were retrieved by searching 12 vascular-related topics, of which 2,225 actual videos (55.7%) were finally confirmed to be related to medicine. Videos for the public accounted for 84.8% of these 2,225 videos. In addition, 50.5% of the video results were uploaded by vascular surgeons, 12.4% by other specialties, 17.7% by organizations, and 19.4% by other individuals. The total number of videos searched for varicose vein and peripheral vascular diseases was the largest, and the total number of leg amputation videos was the smallest. The largest number of videos for medical professionals was about pulmonary embolism, and the smallest was about leg amputation. On the first pages, 168 results (70.0%) were actually medically relevant, and only 7.7% of the videos were uploaded by vascular surgeons. Conclusion: On the Bilibili platform, videos about vascular diseases are extensive but not comprehensive. The videos uploaded by vascular surgeons are rare, and the results searched are not precise. The online presence of vascular surgeons needs to be improved, which may partially solve the problem of low-quality videos due to the lack of strict management and censorship.

Synthetic biology toolkit for engineering Cupriviadus necator H16 as a platform for CO2 valorization.

BACKGROUND: CO2 valorization is one of the effective methods to solve current environmental and energy problems, in which microbial electrosynthesis (MES) system has proved feasible and efficient. Cupriviadus necator (Ralstonia eutropha) H16, a model chemolithoautotroph, is a microbe of choice for CO2 conversion, especially with the ability to be employed in MES due to the presence of genes encoding [NiFe]-hydrogenases and all the Calvin-Benson-Basham cycle enzymes. The CO2 valorization strategy will make sense because the required hydrogen can be produced from renewable electricity independently of fossil fuels. MAIN BODY: In this review, synthetic biology toolkit for C. necator H16, including genetic engineering vectors, heterologous gene expression elements, platform strain and genome engineering, and transformation strategies, is firstly summarized. Then, the review discusses how to apply these tools to make C. necator H16 an efficient cell factory for converting CO2 to value-added products, with the examples of alcohols, fatty acids, and terpenoids. The review is concluded with the limitation of current genetic tools and perspectives on the development of more efficient and convenient methods as well as the extensive applications of C. necator H16. CONCLUSIONS: Great progress has been made on genetic engineering toolkit and synthetic biology applications of C. necator H16. Nevertheless, more efforts are expected in the near future to engineer C. necator H16 as efficient cell factories for the conversion of CO2 to value-added products.