Damage to endothelial barriers and its contribution to long COVID.

The world continues to contend with COVID-19, fueled by the emergence of viral variants. At the same time, a subset of convalescent individuals continues to experience persistent and prolonged sequelae, known as long COVID. Clinical, autopsy, animal and in vitro studies all reveal endothelial injury in acute COVID-19 and convalescent patients. Endothelial dysfunction is now recognized as a central factor in COVID-19 progression and long COVID development. Different organs contain different types of endothelia, each with specific features, forming different endothelial barriers and executing different physiological functions. Endothelial injury results in contraction of cell margins (increased permeability), shedding of glycocalyx, extension of phosphatidylserine-rich filopods, and barrier damage. During acute SARS-CoV-2 infection, damaged endothelial cells promote diffuse microthrombi and destroy the endothelial (including blood-air, blood-brain, glomerular filtration and intestinal-blood) barriers, leading to multiple organ dysfunction. During the convalescence period, a subset of patients is unable to fully recover due to persistent endothelial dysfunction, contributing to long COVID. There is still an important knowledge gap between endothelial barrier damage in different organs and COVID-19 sequelae. In this article, we mainly focus on these endothelial barriers and their contribution to long COVID.

Neutrophil extracellular traps contribute to tissue plasminogen activator resistance in acute ischemic stroke.

Circulating neutrophil extracellular traps (NETs) resistant to t-PA have not been studied completely although NETs in thrombi may contribute to tissue plasminogen activator (t-PA) resistance. This research intended to elucidate whether circulating NETs are associated with t-PA resistance and the underlying mechanism. The levels of NETs were detected in the circulating neutrophils, ischemic brain tissue of acute ischemic stroke (AIS) patients, and transient middle cerebral artery occlusion (tMCAO) models. NET formation in blood, thrombi, and ischemic brain tissue of mice were analyzed by immunofluorescence. Exposed phosphatidylserine (PS) was assessed using flow cytometry and confocal microscopy. Procoagulant activity (PCA) was evaluated using fibrin formation assays, thrombin, and purified coagulation complex. The plasma levels of NETs in AIS patients were significantly higher than those in healthy individuals. After thrombolysis, a significant increase was noted in NET markers in no-improvement patients, while the changes in improvement patients were not significant. Importantly, NETs were decorated with von Willebrand factor (vWF) and plasminogen activator inhibitor-1 (PAI-1) in the blood and thrombi, which could reverse the fibrinolytic effects. In addition, NETs activated platelets (PLTs) and endothelial cells (ECs), stimulating a procoagulant phenotype and facilitating vWF and PAI-1 release. DNase I, activated protein C (APC), and sivelestat markedly inhibited these effects. Furthermore, targeting NETs protected mice from tMCAO-induced cerebral ischemia, possibly by regulating vWF and PAI-1. In summary, NETs may contribute to t-PA resistance in AIS through activation of PLTs and ECs. Strategies against NETs may present a promising therapeutic approach to improve the thrombolysis efficiency of t-PA in AIS patients.

Inhibition of NF-κB by Pyrrolidine Dithiocarbamate Prevents the Inflammatory Response in a Ligature-Induced Peri-Implantitis Model: A Canine Study.

BACKGROUND/AIMS: The roles of toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB) in peri-implantitis are unclear. Here, we used a canine model of peri-implantitis to explore the effects of inhibiting NF-κB with pyrrolidine dithiocarbamate (PDTC) on the inflammatory response in ligature-induced peri-implantitis. METHODS: After successfully establishing the peri-implantitis model, beagles were randomly assigned to normal, model or PDTC groups. ELISA tests were used to determine the levels of interleukin (IL)-1, IL-6, IL-8 and tumor necrosis factor alpha (TNF-α). Immunohistochemistry was employed to assess the expression of NF-κB p65. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to determine the mRNA levels of TLR4 and NF-κB p65, and western blot analysis was used to measure the protein levels of TLR4 in periodontal tissues from each group. Periodontal ligament fibroblasts (PDLFs) were cultured and subsequently classified into PDLF normal, PDLF model, PDLF LPS, PDLF PDTC, and PDLF LPS + PDTC groups. An immunofluorescence assay was used to measure the expression level of NF-κB p65. The CCK-8 assay and flow cytometry were performed to evaluate cell proliferation and apoptosis. RESULTS: The in vitro results indicated that NF-κB p65 and TLR4 were upregulated in canine periodontal tissues, and PDTC could suppress the expression levels of NF-κB p65 and TLR4. Inflammation could increase TLR4 protein expression in canine periodontal tissue, and PDTC could inhibit the inflammation-induced increase in TLR4 protein expression. These results revealed that PDTC could reverse the LPS-induced increases in the levels of IL-1, IL-6, IL-8 and TNF-α. In vivo, the results demonstrated that PDTC inhibited the LPS-induced NF-κB p65 upregulation, and PDTC could reverse the inhibitory effect of the PDLF model + LPS on the proliferation of periodontal fibroblasts. The results also showed that in the PDLF model, LPS promoted PDLF apoptosis by inducing implant periodontitis in canines, but PDTC inhibited the PDLF apoptosis and relieved implant periodontitis in canines. CONCLUSION: Based on our results, we concluded that PDTC can inhibit the expression of NF-κB and alleviate the inflammatory response induced by LPS, thereby preventing periodontal inflammation and reducing the development of peri-implantitis.

New insights into long noncoding RNAs and pseudogenes in prognosis of renal cell carcinoma.

BACKGROUND: Increasing evidence suggests a critical role for long noncoding RNAs (LncRNAs) and pseudogenes in cancer. Renal cell carcinoma (RCC), the most common primary renal neoplasm, is highly aggressive and difficult to treat because of its resistance to chemotherapy and radiotherapy. Despite many identified LncRNAs and pseudogenes, few have been clearly elucidated. METHODS: This study provides new insights into LncRNAs and pseudogenes in the prognosis of RCC. We searched an online database to interrogate alterations and clinical data on cBioPortal. We analysed LncRNA and pseudogene signatures to predict the prognosis of RCC based on a Cox model. We also found potential serum biomarkers of RCC and validated them in 32 RCC patients, as well as healthy controls. RESULTS: Alterations were found in 2553 LncRNAs and 8901 pseudogenes and occurred in up to 23% of all cases. Among these, 27 LncRNAs and 45 pseudogenes were closely related to prognosis. We also identified signatures of LncRNAs and pseudogenes that can predict overall survival and recurrence of RCC. We then validated the relative levels of these LncRNAs and pseudogenes in the serum of 32 patients. Six of these, including LINC00520, PIK3CD-AS1, LINC01559, CEACAM22P, MSL3P1 and TREML3P, could be non-invasive biomarkers of RCC. Finally, we selected PIK3CD-AS1 to determine its role in RCC and found that upregulation of PIK3CD-AS1 was closely associated with higher tumour stage and metastasis. CONCLUSIONS: These signatures of LncRNAs and pseudogenes can predict overall survival and recurrence of RCC. LINC00520, PIK3CD-AS1, LINC01559, CEACAM22P, MSL3P1 and TREML3P could be non-invasive biomarkers of RCC. These data suggest the important roles of LncRNAs and pseudogenes in RCC, and therefore provides us new insights into the prognosis of RCC.

Identification of CDK2 as a novel target in treatment of prostate cancer.

AIM: This study aims the potential gene involved in the metastasis of prostate cancer (Pca). METHODS: PubMed GEO datasets (GSE6605 and GSE6606) were downloaded. We used multiple bioinformatics methods to screen differentially expressed genes in Pca. Gene network was built by STRING and visualized by Cytoscape. All of the hub genes were analyzed by cBioPortal. Inhibition of CDK2 including siRNA, inhibitor and cas9-induced CDK2 knockout was followed by an invasion assay. Downstream genes of CDK2 were analyzed by western blot. RESULTS: Sequencing data were analyzed to screen the genes with expression alterations. The top genes were validated in our samples. 11 hub genes were screened out. Among these genes, STAT3 and CDK2 were significantly associated with recurrence. Further study suggested that inhibition of CDK2 reduced invasion of Pca cell lines. The invasion ability was rescued after reintroduction of CDK2. CONCLUSION: These data indicated that CDK2 was a crucial factor in metastasis of Pca and might be a novel therapy target. [Formula: see text].

[Types for 1 849 patients with urinary calculi and patients' clinical characteristics].

OBJECTIVE: To analyze types of urinary calculi and patients' clinical characteristics, and to explore the strategies for prevention and treatment of urinary calculi.
 Methods: A total of 1 849 patients with urinary calculi were treated in the Department of Urology, the Third Xiangya Hospital of Central South University. The components were analyzed by infrared spectroscopy. The relationship between stone composition and clinical parameters was analyzed according to the clinical characteristics of the patients.
 Results: The proportion of calcium oxalate stone or uric acid stone in male (84.1% or 7.7%) was higher than that in female (78.4% or 4.2%). The older patients were more likely to be diagnosed as uric acid stone. The proportions of uric acid stone in patients <18 years old, 18-<41 years old, 41-<66 years old, and ≥66 years old were 0.0%, 1.6%, 6.6%, and 12.4%, respectively. There was no significant difference in the proportion of stones in patients with different BMI. There were no significant difference in the stone composition between the patients with or without urinary tract infection, hypertension or diabetes. The proportion of uric acid stones in patients with acidic urine was higher than the other types. The proportion of uric acid stones in patients with elevated creatinine (12.1%) was higher than that in the patients with normal creatinine (4.5%).
 Conclusion: Elderly patients, or patients with high uric acid and renal insufficiency are more prone to uric acid stones. Regulation of urinary pH may be an important strategy for preventing and treating urinary calculi in Hunan Province.

Novel Circular RNA CircUBAP2 Drives Tumor Progression by Regulating the miR-143/TFAP2B Axis in Prostate Cancer.

BACKGROUND: More and more investigations reveal that circular RNAs (circRNAs) are involved in cancer progression. CircRNA UBAP2 was closely related to prostate cancer. However, the biological function and specifical mechanism of circUBAP2 are still poorly discovered in prostate cancer (PCa). OBJECTIVES: This study aims to explore the biological function and mechanism of circUBAP2 in PCa. METHODS: The levels of mRNA and proteins were assessed by qRT-PCR assay and Western blot, respectively. Cell growth, migration, and invasion ability were measured using CCK-8 assay and Transwell assay. Apoptosis was assessed using flow cytometry. The interactions between circUBAP2, miR-143, and TFAP2B were determined by luciferase report assay. The tumor growth was determined by in vivo tumor formation assay. The tumor morphology was assessed using H&E staining assay, and immunohistochemistry assay was conducted to assess the level of KI67. RESULTS: We found circUBAP2 and TFAP2B were notably elevated, while miR-143 was largely attenuated in prostate cancer cells and tissues. CircUBAP2 was found to affect cell viability, metastasis and EMT, while attenuating the apoptosis rate of prostate cancer cells. CircUBAP2 directly targeted miR-143, and miR-143 inhibitor could reverse the effects that circUBAP2 interference-induced in prostate cancer cells. TFAP2B is directly bound to miR-143, and overexpression of TFAP2B could attenuate the influences that miR-143-induced in prostate cancer cells. CONCLUSION: CircUBAP2 promoted prostate cancer progression via miR-143/TFAP2B axis.

Efficient and robust estimation of single-vehicle crash severity: A mixed logit model with heterogeneity in means and variances.

This study delves into the factors that contribute to the severity of single-vehicle crashes, focusing on enhancing both computational speed and model robustness. Utilizing a mixed logit model with heterogeneity in means and variances, we offer a comprehensive understanding of the complexities surrounding crash severity. The analysis is grounded in a dataset of 39,788 crash records from the UK's STATS19 database, which includes variables such as road type, speed limits, and lighting conditions. A comparative evaluation of estimation methods, including pseudo-random, Halton, and scrambled and randomized Halton sequences, demonstrates the superior performance of the latter. Specifically, our estimation approach excels in goodness-of-fit, as measured by ρ2, and in minimizing the Akaike Information Criterion (AIC), all while optimizing computational resources like run time and memory usage. This strategic efficiency enables more thorough and credible analyses, rendering our model a robust tool for understanding crash severity. Policymakers and researchers will find this study valuable for crafting data-driven interventions aimed at reducing road crash severity.

The effect of magnesium ions synergistic with mineralized collagen on osteogenesis/angiogenesis properties by modulating macrophage polarizationin vitroandin vivo.

In bone tissue engineering, the bone immunomodulatory properties of biomaterials are critical for bone regeneration, which is a synergistic process involving physiological activities like immune response, osteogenesis, and angiogenesis. The effect of the macrophage immune microenvironment on the osteogenesis and angiogenesis of various material extracts was examined in this experiment using Mg2+and Nano-hydroxyapatite/collagen (nHAC) in both a single application and a combined form. This studyin vitrorevealed that the two compounds combined significantly inhibited the NF-κB signaling pathway and reduced the release of inflammatory factors from macrophages when compared with the extraction phase alone. Additionally, by contributing to the polarization of macrophages towards the M2 type, the combined effects of the two materials can significantly improve osteogenesis/angiogenesis. The results ofin vivoexperiments confirmed that Mg2+/nHAC significantly promoted bone regeneration and angiogenesis. This study offers a promising method for enhancing bone graft material osseointegration.

First-principle study on the photoelectric properties of monolayer h-BN under different strain types.

CONTEXT: Two-dimensional materials are a new and promising research field in materials science. This is mainly attributed to their unique photoelectric and chemical properties. In addition to possessing unique optoelectronic and chemical properties, two-dimensional materials also have important application prospects in the field of field-effect devices. Based on density functional theory, the effects of uniaxial strain and equibiaxial strain on the mechanical properties, electronic structure, and optical properties of monolayer h-BN were studied using first principles. The results indicate that compressive strain has a significant impact on the stability of monolayer h-BN. The band gap width of monolayer h-BN decreases with increasing strain, and the optical properties of monolayer h-BN exhibit a relative trend under tensile and compressive strains. The influence of biaxial strain on the mechanical properties, electronic structure, and optical properties of monolayer h-BN is greater than that of uniaxial strain. METHODS: All the calculations were done by the VASP software based on density functional theory. The interaction between atomic nuclei and electrons is described by the projected added wave pseudopotential (PAW), using the generalized gradient approximation (GGA) to exchange the Perdew-Burke-Ernzerhof (PBE) of the functional. To avoid interlayer interactions, a 15-Å vacuum layer was set up. The Brillouin zone selects the Monkhorst-Pack method to generate 9 × 9 × 1 of k-point grid, the cut off energy is set to 500 eV, the energy convergence standard of the system is 1 × 10-5 eV, and the interaction force between atoms is 0.01 eV/Å.

Effects of Cage Implantation Depth on Sagittal Parameters and Functional Outcomes in Posterior Lumbar Interbody Fusion for the Treatment of L4-L5 Lumbar Degenerative Spondylolisthesis.

OBJECTIVE: In the treatment of lumbar degenerative spondylolisthesis (LDS) with Posterior lumbar interbody fusion (PLIF) surgery, interbody fusion implants play a key role in supporting the vertebral body and facilitating fusion. The objective of this study was to assess the impact of implantation depth on sagittal parameters and functional outcomes in patients undergoing PLIF surgery. METHODS: This study reviewed 128 patients with L4-L5 LDS between January 2016 and August 2019. All patients underwent an open PLIF surgery that included intravertebral decompression, implantation of pedicle screws and cage. We grouped according to the position of the center of the cage relative to the L5 vertebral endplate. Patients with the center of the cage located at the anterior 1/2 of the upper end plate of the L5 vertebral body were divided into Anterior group, and located at the posterior 1/2 of the upper end plate of the L5 vertebral body were divided into Posterior group. The lumbar lordosis (LL), segmental lordosis (SL), sacral slope (SS), pelvic incidence (PI), pelvic tilt (PT) and slope degree (SD) was measured for radiographic outcomes. We used the visual analog scale (VAS) and the oswestry disability index (ODI) score to assess functional outcomes. Paired t-test was used to compare imaging and bedside data before and after surgery between the two groups, and independent sample t-test, χ2 test and Fisher exact test were used to compare the data between the two groups. RESULT: The mean follow-up of Anterior group was 44.13 ± 9.23 months, and Posterior group was 45.62 ± 10.29 months (P > 0.05). The LL, SL, PT, SS, SD and PI-LL after operation showed great improvements, relative to the corresponding preoperative values in both groups (P < 0.05). Compared to Posterior group, Anterior group exhibited far enhanced SL (15.49 ± 3.28 vs. 13.67 ± 2.53, P < 0.05), LL (53.47 ± 3.21 vs. 52.08 ± 3.15, P < 0.05) outcomes and showed depressed PI-LL (8.87 ± 5.05 vs. 10.73 ± 5.39, P < 0.05) outcomes at the final follow-up. Meanwhile, the SL in Anterior group (16.18 ± 3.99) 1 months after operation were also higher than in Posterior group (14.12 ± 3.57) (P < 0.05). We found that VAS and ODI at the final follow-up in Anterior group (3.62 ± 0.96, 25.19 ± 5.25) were significantly lower than those in Posterior group (4.12 ± 0.98, 27.68 ± 5.13) (P < 0.05). CONCLUSIONS: For patients with LDS, the anteriorly placed cage may provide better improvement of SL after PLIF surgery. Meanwhile, the anteriorly placed cage may achieve better sagittal parameters of LL and PI-LL and functional outcomes at the final follow-up.

Enhancement of mitochondrial energy metabolism by melatonin promotes vascularized skeletal muscle regeneration in a volumetric muscle loss model.

Volumetric muscle loss (VML) is a condition that results in the extensive loss of 20 % or more of skeletal muscle due to trauma or tumor ablation, leading to severe functional impairment and permanent disability. The current surgical interventions have limited functional regeneration of skeletal muscle due to the compromised self-repair mechanism. Melatonin has been reported to protect skeletal muscle from exercise-induced oxidative damage and holds great potential to treat muscle diseases. In this study, we hypothesize that melatonin can enhance myoblast differentiation and promote effective recovery of skeletal muscle following VML. In vitro administration of melatonin resulted in a significant enhancement of myogenesis in C2C12 myoblast cells, as evidenced by the up-regulation of myogenic marker genes in a dose-dependent manner. Further experiments revealed that silent information of regulator type 3 (SIRT3) played a critical role in the melatonin-enhanced myoblast differentiation through enhancement of mitochondrial energy metabolism and activation of mitochondrial antioxidant enzymes such as superoxide dismutase 2 (SOD2). Silencing of Sirt3 completely abrogated the protective effect of melatonin on the mitochondrial function of myoblasts, evidenced by the increased reactive oxygen species, decreased adenosine triphosphate production, and down-regulated myoblast-specific marker gene expression. In order to attain a protracted and consistent release, liposome-encapsuled melatonin was integrated into gelatin methacryloyl hydrogel (GelMA-Lipo@MT). The implantation of GelMA-Lipo@MT into a tibialis anterior muscle defect in a VML model effectively stimulated the formation of myofibers and new blood vessels in situ, while concurrently inhibiting fibrotic collagen deposition. The findings of this study indicate that the incorporation of melatonin with GelMA hydrogel has facilitated the de novo vascularized skeletal muscle regeneration by augmenting mitochondrial energy metabolism. This represents a promising approach for the development of skeletal muscle tissue engineering, which could be utilized for the treatment of VML and other severe muscle injuries.

UCNPs-labeled electrospun scaffolds used to monitor in vivo degradation and bone tissue regeneration.

Biodegradable electrospun bone repair materials are effective means to treat bone defects. However, because the electrospun substrates are mostly organic polymer materials, there is a lack of real-time and intuitive monitoring methods for their degradation in vivo. Therefore, it is of great significance to develop in vivo traced electrospun bone repair materials for postoperative observation of their degradation. In this research, polycaprolactone/up-conversion nanoparticles/magnesium oxide (PCL/UCNPs/MgO) composite scaffolds were prepared by electrospun based on the luminescence characteristics of up-conversion nanoparticles (UCNPs) under near infrared excitation and the osteogenic ability of MgO. The in vivo and in vitro degradation results showed that with the increase of time, the electrospun scaffolds gradually degraded and its luminescence intensity decreased. The addition of UCNPs can effectively monitor the degradation of the scaffolds. In addition, the prepared electrospun scaffolds had great biocompatibility, among which PCL-1%UCNPs-1%MgO (P1U1M) electrospun scaffolds had obvious effect on promoting osteogenic differentiation of mouse embryonic osteoblasts cells (MC3T3-E1) in vitro. In conclusion, P1U1M electrospun scaffolds have the potential to induce bone regeneration at bone defect sites, and can monitor the degradation of electrospun scaffolds. It may be a potential candidate material for bone regeneration in defect area.

PCL-nHAC/Mg-Ca alloy composite and preliminary study of its osteogenesis property.

Owing to their excellent properties, magnesium alloys are widely used in bone tissue engineering. However, considerable work has been conducted to control the degradation rate and improve the cytocompatibility of magnesium alloys. In this study, low-cost production introduced a new bone repair composite (PCL-nHAC/Mg-Ca), which was composed of nano-hydroxylapatite-collagen (nHAC), polycaprolactone (PCL) and Mg-Ca alloy substrate treated by micro- arc oxidation (MAO). The experimental results showed that compared with the Mg-Ca alloy treated by MAO alone, the PCL-nHAC/Mg-Ca composite has a porous structure and a slower degradation rate. Cell experiments showed that the PCL-nHAC/Mg-Ca composite had good biocompatibility and significantly enhanced the proliferation of the MC3T3-E1 cells. The rabbit skull defect model further proved that the PCL-nHAC/Mg-Ca composite could regulate the degradation rate of the Mg-Ca alloy and promote the formation of bone tissue. Histological analyses showed that the PCL-nHAC/Mg-Ca composite had good stability in vivo and could better accelerate bone formation.

Microparticle Phosphatidylserine Mediates Coagulation: Involvement in Tumor Progression and Metastasis.

Tumor progression and cancer metastasis has been linked to the release of microparticles (MPs), which are shed upon cell activation or apoptosis and display parental cell antigens, phospholipids such as phosphatidylserine (PS), and nucleic acids on their external surfaces. In this review, we highlight the biogenesis of MPs as well as the pathophysiological processes of PS externalization and its involvement in coagulation activation. We review the available evidence, suggesting that coagulation factors (mainly tissue factor, thrombin, and fibrin) assist in multiple steps of tumor dissemination, including epithelial-mesenchymal transition, extracellular matrix remodeling, immune escape, and tumor angiogenesis to support the formation of the pre-metastatic niche. Platelets are not just bystander cells in circulation but are functional players in primary tumor growth and metastasis. Tumor-induced platelet aggregation protects circulating tumor cells (CTCs) from the blood flow shear forces and immune cell attack while also promoting the binding of CTCs to endothelial cells and extravasation, which activates tumor invasion and sustains metastasis. Finally, in terms of therapy, lactadherin can inhibit coagulation by competing effectively with coagulation factors for PS binding sites and may similarly delay tumor progression. Furthermore, we also investigate the therapeutic potential of coagulation factor inhibitors within the context of cancer treatment. The development of multiple therapies targeting platelet activation and platelet-tumor cell interactions may not only reduce the lethal consequences of thrombosis but also impede tumor growth and spread.

Optimization of the processing technology of schizonepetae herba carbonisata using response surface methodology and artificial neural network and comparing the chemical profiles between raw and charred schizonepetae herba by UPLC-Q-TOF-MS.

In this study, response surface methodology (RSM) and artificial neural network (ANN) were used to predict and validate the optimal processing method of Schizonepetae Herba Carbonisata (SHC). The highest overall desirability (OD) value of the total flavonoids content (TFC), total tannin content (TTC), and adsorption capacity (AC) were used as response values. The optimal processing technology processing time lasted 10 min at a processing temperature of 178 °C and the herbs/machine had a volume of 77 g/5 L. The Ultra Performance Liquid Chromatography/Quadrupole Time-of-Flight Mass Spectrometry (UPLC-Q-TOF-MS), combined with chemometrics, was used to investigate the changes of compounds in Schizonepetae Herba (SH) before and after being charred. A total of 104 compounds were tentatively identified in SH and 83 in SHC. Fifteen differential compounds were found between by chemometrics SH and SHC. Altogether, our findings can provide a practical approach to the processing technology of carbonizing by stir-frying SH.

In vitro evaluation of freeze-drying chitosan-mineralized collagen/Mg-Ca alloy composites for osteogenesis.

Magnesium (Mg) alloy with good mechanical properties and biodegradability is considered as one of the ideal bone repair materials. However, the rapid corrosion of Mg-based metals can pose harm to the function of an implant in clinical applications. In this study, micro-arc oxidation coating was prepared on the surface of the Mg-Ca matrix, then the chitosan and mineralized collagen (nano-hydroxyapatite/collagen; nHAC) were immobilized on the surface of the MAO/Mg-Ca matrix to construct the CS-nHAC/Mg-Ca composites of different component proportions (the ratio of CS to nHAC is 2:1, 1:1, and 1:2, respectively). The corrosion resistance, osteogenic activity, and angiogenic ability were extensively investigated. The results indicated that the CS-nHAC reinforcement materials can improve the corrosion resistance of the Mg matrix significantly and promote the proliferation and adhesion of mouse embryo osteoblast precursor cells (MC3T3-E1) and human umbilical vein endothelial cells (HUVECs). In addition, the CS-nHAC/Mg-Ca composites can not only promote the alkaline phosphatase (ALP) activity and extracellular matrix mineralization of MC3T3-E1 cells but also enhance the migration motility and vascular endothelial growth factor (VEGF) expression of HUVECs. Meanwhile, the 2CS-1nHAC/Mg-Ca composite exhibited the optimum function characteristics compared with other samples. Therefore, considering the improvement of corrosion resistance and biocompatibility, the CS-nHAC/Mg-Ca composites are expected to be a promising orthopedic implant.

Persistent Lung Injury and Prothrombotic State in Long COVID.

Lung injury may persist during the recovery period of COVID-19 as shown through imaging, six-minute walk, and lung function tests. The pathophysiological mechanisms leading to long COVID have not been adequately explained. Our aim is to investigate the basis of pulmonary susceptibility during sequelae and the possibility that prothrombotic states may influence long-term pulmonary symptoms of COVID-19. The patient's lungs remain vulnerable during the recovery stage due to persistent shedding of the virus, the inflammatory environment, the prothrombotic state, and injury and subsequent repair of the blood-air barrier. The transformation of inflammation to proliferation and fibrosis, hypoxia-involved vascular remodeling, vascular endothelial cell damage, phosphatidylserine-involved hypercoagulability, and continuous changes in serological markers all contribute to post-discharge lung injury. Considering the important role of microthrombus and arteriovenous thrombus in the process of pulmonary functional lesions to organic lesions, we further study the possibility that prothrombotic states, including pulmonary vascular endothelial cell activation and hypercoagulability, may affect long-term pulmonary symptoms in long COVID. Early use of combined anticoagulant and antiplatelet therapy is a promising approach to reduce the incidence of pulmonary sequelae. Essentially, early treatment can block the occurrence of thrombotic events. Because impeded pulmonary circulation causes large pressure imbalances over the alveolar membrane leading to the infiltration of plasma into the alveolar cavity, inhibition of thrombotic events can prevent pulmonary hypertension, formation of lung hyaline membranes, and lung consolidation.

Study on the angiogenesis ability of Polymethyl methacrylate-mineralized collagen/Mg-Ca composite material in vitro and the bone formation effect in vivo.

Magnesium (Mg) and its alloys show high degrees of biocompatibility and biodegradability, used as biodegrad able materials in biomedical applications. In this study, Polymethyl methacrylate (PMMA) - mineralized collagen (nano-Hydroxyapatite/collagen; nHAC)/Mg-Ca composite materials were prepared, to study the angiogenesis ability of its composite materials on Human umbilical vein endothelial cells (HUVECs) and its osteogenesis effect in vivo. The results showed that the PMMA-nHAC reinforcement materials can promote the proliferation and adhesion in HUVECs of Mg matrix significantly, it can enhance the migration motility and VEGF expression of HUVECs. In vivo, Micro-CT examination showed that with coated samples presenting the highest bone formation. Histologically, the materials and their corrosion products caused no systematic or local cytotoxicological effects. Therefore, the Mg matrix composites prepared in the present study has good biocompatibility and PMMA-nHAC/Mg-Ca composite may be an ideal orthopedic material to improve the bone formation, and biodegradable magnesium based implants with bioactivity have potential applications in bone tissue.

Long COVID: The Nature of Thrombotic Sequelae Determines the Necessity of Early Anticoagulation.

Many discharged COVID-19 patients affected by sequelae experience reduced quality of life leading to an increased burden on the healthcare system, their families and society at large. Possible pathophysiological mechanisms of long COVID include: persistent viral replication, chronic hypoxia and inflammation. Ongoing vascular endothelial damage promotes platelet adhesion and coagulation, resulting in the impairment of various organ functions. Meanwhile, thrombosis will further aggravate vasculitis contributing to further deterioration. Thus, long COVID is essentially a thrombotic sequela. Unfortunately, there is currently no effective treatment for long COVID. This article summarizes the evidence for coagulation abnormalities in long COVID, with a focus on the pathophysiological mechanisms of thrombosis. Extracellular vesicles (EVs) released by various types of cells can carry SARS-CoV-2 through the circulation and attack distant tissues and organs. Furthermore, EVs express tissue factor and phosphatidylserine (PS) which aggravate thrombosis. Given the persistence of the virus, chronic inflammation and endothelial damage are inevitable. Pulmonary structural changes such as hypertension, embolism and fibrosis are common in long COVID. The resulting impaired lung function and chronic hypoxia again aggravates vascular inflammation and coagulation abnormalities. In this article, we also summarize recent research on antithrombotic therapy in COVID-19. There is increasing evidence that early anticoagulation can be effective in improving outcomes. In fact, persistent systemic vascular inflammation and dysfunction caused by thrombosis are key factors driving various complications of long COVID. Early prophylactic anticoagulation can prevent the release of or remove procoagulant substances, thereby protecting the vascular endothelium from damage, reducing thrombotic sequelae, and improving quality of life for long-COVID patients.