A taurine-based hydrogel with the neuroprotective effect and the ability to promote neural stem cell proliferation.

Ischemic stroke, a cerebrovascular disease caused by arterial occlusion in the brain, can lead to brain impairment and even death. Stem cell therapies have shown positive advantages to treat ischemic stroke because of their extended time window, but the cell viability is poor when transplanted into the brain directly. Therefore, a new hydrogel GelMA-T was developed by introducing taurine on GelMA to transplant neural stem cells. The GelMA-T displayed the desired photocuring ability, micropore structure, and cytocompatibility. Its compressive modulus was more similar to neural tissue compared to that of GelMA. The GelMA-T could protect SH-SY5Y cells from injury induced by OGD/R. Furthermore, the NE-4C cells showed better proliferation performance in GelMA-T than that in GelMA during both 2D and 3D cultures. All results demonstrate that GelMA-T possesses a neuroprotective effect for ischemia/reperfusion injury against ischemic stroke and plays a positive role in promoting NSC proliferation. The novel hydrogel is anticipated to function as cell vehicles for the transplantation of neural stem cells into the stroke cavity, aiming to treat ischemic stroke.

Catalpol promotes articular cartilage repair by enhancing the recruitment of endogenous mesenchymal stem cells.

Articular cartilage defect is challenged by insufficient regenerative ability of cartilage. Catalpol (CA), the primary active component of Rehmanniae Radix, could exert protective effects against various diseases. However, the impact of CA on the treatment of articular cartilage injuries is still unclear. In this study, full-thickness articular cartilage defect was induced in a mouse model via surgery. The animals were intraperitoneally injected with CA for 4 or 8 weeks. According to the results of macroscopic observation, micro-computed tomography CT (µCT), histological and immunohistochemistry staining, CA treatment could promote mouse cartilage repair, resulting in cartilage regeneration, bone structure improvement and matrix anabolism. Specifically, an increase in the expression of CD90, the marker of mesenchymal stem cells (MSCs), in the cartilage was observed. In addition, we evaluated the migratory and chondrogenic effects of CA on MSCs. Different concentration of CA was added to C3H10 T1/2 cells. The results showed that CA enhanced cell migration and chondrogenesis without affecting proliferation. Collectively, our findings indicate that CA may be effective for the treatment of cartilage defects via stimulation of endogenous MSCs.

HBV integrations reshaping genomic structures promote hepatocellular carcinoma.

OBJECTIVE: Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), mostly characterised by HBV integrations, is prevalent worldwide. Previous HBV studies mainly focused on a few hotspot integrations. However, the oncogenic role of the other HBV integrations remains unclear. This study aimed to elucidate HBV integration-induced tumourigenesis further. DESIGN: Here, we illuminated the genomic structures encompassing HBV integrations in 124 HCCs across ages using whole genome sequencing and Nanopore long reads. We classified a repertoire of integration patterns featured by complex genomic rearrangement. We also conducted a clustered regularly interspaced short palindromic repeat (CRISPR)-based gain-of-function genetic screen in mouse hepatocytes. We individually activated each candidate gene in the mouse model to uncover HBV integration-mediated oncogenic aberration that elicits tumourigenesis in mice. RESULTS: These HBV-mediated rearrangements are significantly enriched in a bridge-fusion-bridge pattern and interchromosomal translocations, and frequently led to a wide range of aberrations including driver copy number variations in chr 4q, 5p (TERT), 6q, 8p, 16q, 9p (CDKN2A/B), 17p (TP53) and 13q (RB1), and particularly, ultra-early amplifications in chr8q. Integrated HBV frequently contains complex structures correlated with the translocation distance. Paired breakpoints within each integration event usually exhibit different microhomology, likely mediated by different DNA repair mechanisms. HBV-mediated rearrangements significantly correlated with young age, higher HBV DNA level and TP53 mutations but were less prevalent in the patients subjected to prior antiviral therapies. Finally, we recapitulated the TONSL and TMEM65 amplification in chr8q led by HBV integration using CRISPR/Cas9 editing and demonstrated their tumourigenic potentials. CONCLUSION: HBV integrations extensively reshape genomic structures and promote hepatocarcinogenesis (graphical abstract), which may occur early in a patient's life.

The real-world incidence and predictors of sac regression in patients with infrarenal abdominal aortic aneurysm after standard EVAR.

OBJECTIVE: Sac regression (SR) is a surrogate marker of satisfied endovascular aneurysm repair (EVAR). This research aims to investigate the incidence and predictors of SR in a Chinese population. DESIGN: Single centre retrospective cohort study. METHODS: Consecutive patients with infrarenal abdominal aortic aneurysms (AAAs) who underwent standard EVAR were retrospectively reviewed. SR was defined as sac shrinkage > 5 mm on computed tomography images, while major SR (MaSR) was ≥ 10 mm sac shrinkage. The cumulative rate was calculated by Kaplan-Meier analysis and predictors were identified by the Cox regression model. RESULTS: A total of 469 patients (median age, 71 years old) were included. The majority of them (86.6 %) were male. With a median time of 13.6 months, SR was detected in 129 (27.5 %) patients after the index EVAR. Compared with never smokers, current smokers were more likely to experience SR (adjusted HR 2.630, p < .001), while former smokers did not show any significant difference. Multivariate Cox regression also showed that maximal aneurysm diameter (adjusted HR 1.012, p = 0.035) and female (adjusted HR 1.675, p = .045) were independent predictors of SR. A total of 51 (10.9 %) patients had MaSR at a median time of 15.4 months after EVAR. In multivariate analysis, maximal aneurysm diameter and Zenith stent graft were independently associated with MaSR. CONCLUSION: In Chinese population, the incidence of SR and MaSR was 27.5 % and 10.9 % after EVAR, respectively. Maximal aneurysm diameter and female were independent predictors of SR. Compared with never smokers, it was more likely to have SR in current smokers.

Principles of Optimal Antithrombotic Therapy for Iliac VEnous Stenting (POATIVES): A national expert-based Delphi consensus study.

OBJECTIVE: Management of antithrombotic therapy in patients undergoing venous stents has not yet reached consensus, and there are not any recommendations from published guidelines. We undertook a Delphi consensus from Chinese experts to develop recommendations regarding the preferred antithrombotic therapy in patients following venous stenting. METHODS: The phase 1 questionnaire was comprised of three clinical scenarios of venous stenting for non-thrombotic iliac vein lesions (NIVL), acute deep vein thrombosis (DVT), and post-thrombotic syndrome (PTS) and was sent to venous practitioners across China. In phase 2, the results of phase 1 were distributed to a panel of experts for evaluation along with a questionnaire encompassing a series of statements produced during phase 1. A modified Delphi method was used to reach consensus on recommendations through two rounds of surveys. RESULTS: The phase 1 questionnaire was completed by 283 respondents. In phase 2, an expert panel consisting of 28 vascular surgeons and interventional radiologists was assembled and voted 17 statements relating to antithrombotic management after venous stenting for NIVL (4 statements), DVT (6 statements), and PTS (7 statements). The majority of the statements about the antithrombotic agent selection received a high consensus strength. CONCLUSIONS: Based on the national Delphi consensus of Chinese experts regarding antithrombotic therapy following iliac venous stenting in three common scenarios, most of the statements could be used to guide antithrombotic management following venous stenting. Further studies are required to clarify controversial issues including the dose and duration of anticoagulants, the role of antiplatelet agents, especially in patients with NIVL.

[Risk Assessment of Heavy Metals in Dust Fall Around Reservoirs in Typical Ecologically Fragile Areas and Traceability Based on APCS-MLR Model].

To assess the health risk status and pollution sources of heavy metals in the atmosphere of ecologically vulnerable areas, the surrounding area of Dahekou Reservoir in Xilingol League was selected as the study area. From 2021 to 2022, 12 monitoring points for atmospheric dust fall were collected for a period of one year. A total of 144 samples were collected to determine the contents of eight types of heavy metals, namely Cr, Ni, Pb, Cu, Zn, Mn, As, and Cd. The potential ecological index (Eri) and health risk assessment model were used to assess the risk level of atmospheric heavy metals on ecological security and human health. The analysis of enrichment factors, principal components, and the model of absolute principal component multiple linear regression (APCS-MLR) receptor were used to analyze the sources of heavy metal pollution qualitatively in the atmosphere of the study area. The results showed that:① the mean value of the comprehensive potential ecological risk of heavy metals in the annual atmospheric dust fall in the study area was at a high ecological risk, and only the Cd value was at a very high risk level among the heavy metals, whereas the remaining were at a slight risk. ② The results of the health risk showed that intake by hand, mouth, and skin contact were the main exposure routes, which led to non-carcinogenic and carcinogenic risks. Children were under non-carcinogenic and acceptable carcinogenic risks in different months. During those months, the main source of the risks was As. ③ Through enrichment factor analysis, principal component analysis, and APCS-MLR receptor model calculation, the results revealed that the proportion of wind-blown sources was the largest, accounting for 37.82%, and the contribution rates of coal combustion and traffic sources to Cu, Cd, Pb, and Zn were 73.01%, 40.22%, 70.31%, and 32.82%, respectively. The contribution rate of mining activities to As was 42.59%, while that of industrial sources of Cd was 22.01%; the contributions of other human activity sources of Cd, As, Pb, and Zn were 21.12%, 34.40%, 23.04%, and 32.15%, respectively.

3D printed PEKK bone analogs with internal porosity and surface modification for mandibular reconstruction: An in vivo rabbit model study.

Polyetheretherketone (PEEK) and its derivative polyetherketoneketone (PEKK) have been used as implant materials for spinal fusing and enjoyed their success for many years because of their mechanical properties similar to bone and their chemical inertness. The osseointegration of PEEKs is datable. Our strategy was to use custom-designed and 3D printed bone analogs with an optimized structure design and a modified PEKK surface to augment bone regeneration for mandibular reconstruction. Those bone analogs had internal porosities and a bioactive titanium oxide surface coating to promote osseointegration between native bone and PEKK analogs. Our workflow was 3D modeling, bone analog designing, structural optimization, mechanical analysis via finite element modeling, 3D printing of bone analogs and subsequently, an in vivo rabbit model study on mandibular reconstruction and histology evaluation. Our results showed the finite element analysis validated that the porous PEKK analogs provided a mechanical-sound structure for functional loadings. The bone analogs offered a perfect replacement for segmented bones in the terms of shape, form and volume for surgical reconstruction. The in vivo results showed that bioactive titanium oxide coating enhanced new bone in-growth into the porous PEKK analogs. We have validated our new approach in surgical mandibular reconstruction and we believe our strategy has a significant potential to improve mechanical and biological outcomes for patients who require mandibular reconstruction procedures.

Protein phosphatase PPM1A inhibition attenuates osteoarthritis via regulating TGF-ß/Smad2 signaling in chondrocytes.

TGF-ß signaling is crucial for modulating osteoarthritis (OA), and protein phosphatase magnesium-dependent 1A (PPM1A) has been reported as a phosphatase of SMAD2 and regulates TGF-ß signaling, while the role of PPM1A in cartilage homeostasis and OA development remains largely unexplored. In this study, we found increased PPM1A expression in OA chondrocytes and confirmed the interaction between PPM1A and phospho-SMAD2 (p-SMAD2). Importantly, our data show that PPM1A KO substantially protected mice treated with destabilization of medial meniscus (DMM) surgery against cartilage degeneration and subchondral sclerosis. Additionally, PPM1A ablation reduced the cartilage catabolism and cell apoptosis after the DMM operation. Moreover, p-SMAD2 expression in chondrocytes from KO mice was higher than that in WT controls with DMM induction. However, intraarticular injection with SD-208, repressing TGF-ß/SMAD2 signaling, dramatically abolished protective phenotypes in PPM1A-KO mice. Finally, a specific pharmacologic PPM1A inhibitor, Sanguinarine chloride (SC) or BC-21, was able to ameliorate OA severity in C57BL/6J mice. In summary, our study identified PPM1A as a pivotal regulator of cartilage homeostasis and demonstrated that PPM1A inhibition attenuates OA progression via regulating TGF-ß/SMAD2 signaling in chondrocytes and provided PPM1A as a potential target for OA treatment.

Predictive Value of Laboratory Indicators for Endoleak During Short-Term Follow-Up After EVAR.

BACKGROUND: The aim of this study was to explore the predictive value of endoleak in short-term follow-up after endovascular aortic repair (EVAR) of abdominal aortic aneurysm (AAA) via perioperative laboratory indicators. METHODS: A retrospective study included 200 consecutive patients who received standard EVAR treatment for AAA and were followed-up for 1 year. Binary logistic regression analysis was used to evaluate the correlation of the level and changes of perioperative laboratory indicators with the endoleak events during the follow-up. The receiver operating characteristic (ROC) curve was used to assess the predictive value of laboratory indicators for endoleak. RESULTS: A total of 45 cases of endoleak events occurred during follow-up. Binary logistic regression analysis showed that postoperative fibrinogen decrease, perioperative lymphocyte difference and lymphocyte monocyte ratio (LMR) difference were independent risk factors for short term endoleak. The area under the ROC curve (AUC) of postoperative fibrinogen was 0.596, the cut-off value was 284 mg/dl, and the corresponding specificity and sensitivity were 0.644 and 0.568. The AUC of the lymphocyte difference was 0.622, the cut-off value was -0.45 × 109/L, and the corresponding specificity and sensitivity were 0.651 and 0.568. The AUC of the LMR difference was 0.597, the cut-off value was -1.719, and the corresponding specificity and sensitivity were 0.631 and 0.614. CONCLUSIONS: Decrease of postoperative fibrinogen, increase of lymphocyte difference and LMR difference were independent predictive factors for endoleak in short-term follow-up after EVAR for AAA.

Novel nomograms for predicting the risk of low distal bone strength: development and validation in a Chinese population-based observational study.

BACKGROUND: This study aims to develop nomogram models based on the speed of sound (SOS) measurements results along with demographic information to predict the risk of low bone strength (LBS) of radius appropriate to the Chinese population of a broad age spectrum. METHODS: A population-based cross-sectional study was conducted in 5 outpatient clinics located in Zhejiang, the southern part of China. A total of 38,699 participants from 2013 to 2017 were included. Baseline measurements included SOS of the distal radius and clinical risk factor evaluation. Logistic regression models were used to evaluate prognosis and identify independent predictive factors, which were then utilized to establish nomograms for predicting the low bone strength of radius. The discrimination and calibration of nomograms were validated using the calibration plots, the decision curve analysis (DCA), and the receiver operating characteristics curve (ROC). RESULTS: A total of 19,845 of the 38,904 participants ranged in age from 10 to 88 years were selected in this process. LBP nomogram model 1 was constructed based on age, weight, height, BMI, and gender. LBP nomogram model 2 was constructed based on age, height, BMI, and gender. The AUCs for model 1 and model 2 were 0.838 (95% CI: 0.832-0.844) and 0.837 (95% CI: 0.831-0.843), respectively. High-quality calibration plots and DCA in nomogram models were noticed, indicated that the constructed nomogram models were clinically useful. CONCLUSIONS: Our study demonstrates that the nomograms established in this study could effectively evaluate the high-risk population groups of distal radius fracture in China.

Mid-term outcomes of microfragmented adipose tissue plus arthroscopic surgery for knee osteoarthritis: A randomized, active-control, multicenter clinical trial.

BACKGROUND: Osteoarthritis (OA) is the most prevalent form of degenerative whole-joint disease. Before the final option of knee replacement, arthroscopic surgery was the most widely used joint-preserving surgical treatment. Emerging regenerative therapies, such as those involving platelet-rich plasma, mesenchymal stem cells, and microfragmented adipose tissue (MFAT), have been pushed to the forefront of treatment to prevent the progression of OA. Currently, MFAT has been successfully applied to treat different types of orthopedic diseases. AIM: To assess the efficacy and safety of MFAT with arthroscopic surgery in patients with knee OA (KOA). METHODS: A randomized, multicenter study was conducted between June 2017 and November 2022 in 10 hospitals in Zhejiang, China. Overall, 302 patients diagnosed with KOA (Kellgren-Lawrence grades 2-3) were randomized to the MFAT group (n = 151, were administered MFAT following arthroscopic surgery), or the control group (n = 151, were administered hyaluronic acid following arthroscopic surgery). The study outcomes were changes in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, the visual analog scale (VAS) score, the Lequesne index score, the Whole-Organ Magnetic Resonance Imaging Score (WORMS), and safety over a 24-mo period from baseline. RESULTS: The changes in the WOMAC score (including the three subscale scores), VAS pain score, and Lequesne index score at the 24-mo mark were significantly different in the MFAT and control groups, as well as when comparing values at the posttreatment visit and those at baseline (P < 0.001). The MFAT group consistently demonstrated significant decreases in the WOMAC pain scores and VAS scores at all follow-ups compared to the control group (P < 0.05). Furthermore, the WOMAC stiffness score, WOMAC function score, and Lequesne index score differed significantly between the groups at 12 and 24 mo (P < 0.05). However, no significant between-group differences were observed in the WORMS at 24 mo (P = 0.367). No serious adverse events occurred in both groups. CONCLUSION: The MFAT injection combined with arthroscopic surgery treatment group showed better mid-term clinical outcomes compared to the control group, suggesting its efficacy as a therapeutic approach for patients with KOA.

Shenhuang plaster ameliorates the Inflammation of postoperative ileus through inhibiting PI3K/Akt/NF-κB pathway.

BACKGROUND: Although Shenhuang plaster (SHP) from traditional Chinese medicine prescriptions, has the potential to promote the recovery progression of postoperative ileus (POI), the underlying mechanism remains elusive. Along these lines, in this work, both in vivo and in vitro studies were conducted to systematically explore the regulatory effect and mechanism of SHP on the inflammatory response of the intestinal basal layer in the POI model mice. METHODS: Intestinal manipulation in mice was utilized for the POI model. The impact of SHP in response to POI was evaluated by carrying fluorescein-labeled dextran, histomorphology, immunohistochemistry, in combination with flow cytometry analysis and transcriptome RNA sequencing in vivo. Besides, the cytotoxicity of the SHP treatment on RAW264.7 cells was detected by cell counting kit-8 (CCK-8), the biological effects were assessed by polymerase chain reaction (PCR) and the potential influences on the PI3K/Akt/NF-κB pathway were identified through detecting the expression levels of P85, AKT, IKK and P65 by western blot in vitro. RESULTS: The implementation of the SHP treatment could significantly reduce the expressions of interleukin (IL)- 1ß and tumor necrosis factor (TNF)-α in the intestine, whereas the recovery of gastrointestinal motility is promoted. In addition, SHP can regulate the polarization of macrophages, indicating that the proportion of the M2 type is increased after the application of the SHP treatment. In addition, SHP inhibited the activity of PI3K/AKT/NF-κB signaling pathway-related proteins. CONCLUSION: SHP can significantly ameliorate the inflammatory response of POI and at the same time promote the recovery of gastrointestinal motility. Its mechanism may be mediated by the polarization of macrophages through the PI3K/AKT/NF-κB signaling pathway.

Elucidation of the Underlying Mechanism of Gujian Oral Liquid Acting on Osteoarthritis through Network Pharmacology, Molecular Docking, and Experiment.

Gujian oral liquid (GJ), a traditional herbal formula in China, has been widely used to treat patients with osteoarthritis (OA). Nevertheless, the active component and potential mechanism of GJ are not fully elucidated. Thus, we investigate the effect of GJ and explore its underlying mechanism on OA through network pharmacology and experimental validation. First, a total of 175 bioactive compounds were identified, and 134 overlapping targets were acquired after comparing the targets of the GJ with those of OA. 8 hub targets, including IL6 and AKT1, were obtained in PPI network analysis. Then, we built up GJ-target-OA network and protein-protein interaction (PPI) network, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The results underlined inflammatory tumor necrosis factor (TNF) as a promising signaling pathway of GJ for OA treatment. Moreover, molecular docking also verified the top two active compounds had direct bindings with the top three target genes. Finally, we verified the effect of GJ on OA in vivo and in vitro. In vivo experiments validated that GJ not only significantly attenuated OA phenotypes including articular cartilage degeneration and subchondral bone sclerosis but also reduced the expressions of tumor necrosis factor-α (TNF-α) and p-p65 in articular chondrocytes. Besides, GJ serum also had a protective effect on chondrocytes against inflammation caused by TNF-α in vitro. Hence, our study predicted and verified that GJ could exert anti-inflammation and anticatabolism effects partially via regulating TNF-α/NF-kappa B (NF-κB) signaling.

Hemophilia A developing cerebral infarction after surgical treatment of giant hemophilic pseudotumor: a case report.

BACKGROUND: Cerebral infarction (CI) is an unusual complication in patients with bleeding disorders. To our knowledge, this is the first case of postoperative internal border-zone infarction (I-BZI) from Hemophilia A. CASE PRESENTATION: We present a case of Hemophilia A developing I-BZI, after surgical treatment of giant hemophilic pseudotumor. A 36-year-old man was introduced from other hospital by Hemophilia with giant hemophilic pseudotumor in his left thigh. Patient and his relatives did not have a history of thrombophilia. After excluding the relevant surgical contraindications, we performed the operation of pseudotumor resection. Prior to surgery, blood tests revealed hemoglobin of 137 g/L. FVIII activity was 1.5%. Activated partial thromboplastin time (APTT) was 71.50 s and D-dimer was 3.33 mg/L FEU. Immediately before surgery, the patient received an intravenous infusion of FVIII products (Xyntha®) at a dose of 3500 IU for his body weight of 80 kg. Post-operative day two (POD2), patient developed vomiting, decreased response, and dysarthria. Hemoglobin was 54 g/L with blood pressure of 110/70 mmHg. Magnetic resonance imaging of the brain showed there were multiple acute cerebral infarctions in bilateral lateral ventricles (internal border zone) and multiple ischemic foci in the white matter areas and basal ganglia of the bilateral cerebral hemispheres. This case suggested that acute severe anemia can be one of the causes of I-BZI. CONCLUSIONS: For the treatment of I-BZI caused by acute anemia from Hemophilia A, volume expansion, red blood cell supplement and continuous improvement of coagulation with suitable dose of factor VIII (FVIII) should be considered to improve prognosis.

Integrated analysis of genes encoding ATP-dependent chromatin remodellers identifies CHD7 as a potential target for colorectal cancer therapy.

BACKGROUND: Genes participating in chromatin organization and regulation are frequently mutated or dysregulated in cancers. ATP-dependent chromatin remodelers (ATPCRs) play a key role in organizing genomic DNA within chromatin, therefore regulating gene expression. The oncogenic role of ATPCRs and the mechanism involved remains unclear. METHODS: We analyzed the genomic and transcriptional aberrations of the genes encoding ATPCRs in The Cancer Genome Atlas (TCGA) cohort. A series of cellular experiments and mouse tumor-bearing experiments were conducted to reveal the regulatory function of CHD7 on the growth of colorectal cancer cells. RNA-seq and ATAC-seq approaches together with ChIP assays were performed to elucidate the downstream targets and the molecular mechanisms. RESULTS: Our data showed that many ATPCRs represented a high frequency of somatic copy number alterations, widespread somatic mutations, remarkable expression abnormalities, and significant correlation with overall survival, suggesting several somatic driver candidates including chromodomain helicase DNA-binding protein 7 (CHD7) in colorectal cancer. We experimentally demonstrated that CHD7 promotes the growth of colorectal cancer cells in vitro and in vivo. CHD7 can bind to the promoters of target genes to maintain chromatin accessibility and facilitate transcription. We found that CHD7 knockdown downregulates AK4 expression and activates AMPK phosphorylation, thereby promoting the phosphorylation and stability of p53 and leading to the inhibition of the colorectal cancer growth. Our muti-omics analyses of ATPCRs across large-scale cancer specimens identified potential therapeutic targets and our experimental studies revealed a novel CHD7-AK4-AMPK-p53 axis that plays an oncogenic role in colorectal cancer.

Hypoxia Promotes Human Umbilical Vein Smooth Muscle Cell Phenotypic Switching via the ERK 1/2/c-fos/NF-κB Signaling Pathway.

BACKGROUND: Vein wall hypoxia has long been suggested as a key factor for the development of varicose veins (VVs) and accumulating evidence has revealed the phenotypic transformation of vascular smooth muscle cells (VSMCs) under hypoxic conditions. However, the underlying molecular mechanisms of this process remain poorly understood. Our previous study revealed a positive correlation between c-fos expression and VSMC functional disturbance of VVs. This study aimed to further explore the role of c-fos in the phenotypic switching of VSMCs under hypoxic conditions. METHODS: Human umbilical vein smooth muscle cells (HUVSMCs) were cultured under hypoxia or normoxia. PD0325901 (10 µmol/L) and pyrrolidine dithiocarbamate (PDTC) (10 µmol/L) were used to inhibit the extracellular signal-regulated kinase 1/2 (ERK1/2) and nuclear factor-κ B (NF-κB) signaling pathways, respectively. HUVSMCs stably overexpressing c-fos were constructed to explore the underlying mechanism. The Western blot analysis was performed to detect the protein expression levels of c-fos, phosphorylated p65 (p-p65), interleukin-1ß (IL-1ß), cyclooxygenase-2 (COX-2), osteopontin (OPN), and α-smooth muscle actin (α-SMA). Cell proliferation and migration capacity were detected by a Cell Counting Kit 8 (CCK-8) assay and a wound-healing assay, respectively. The cell apoptotic rate was determined using the Annexin V-FITC Apoptosis Detection Kit. RESULTS: Hypoxic exposure increased the expression levels of indicators of the p-ERK1/2/c-fos and NF-κB signaling pathways, which was accompanied by altered levels of phenotypic biomarkers (α-SMA and OPN). Cells exposed to hypoxia were characterized by a greater proliferative and migratory ability. No significant differences were observed in the rate of cell apoptosis between the normal group and the hypoxic group. In addition, inhibition of the ERK1/2/c-fos signaling pathway by PD0325901 (10 µmol/L) reduced the expression of inflammatory cytokines and attenuated hypoxia-mediated phenotypic transformation. Furthermore, inhibition of the NF-κB signaling pathway by PDTC (10 µmol/L) downregulated the expression level of OPN and reduced the migration of HUVSMCs under hypoxia exposure. However, pretreatment with PDTC did not suppress the expression of c-fos or cell proliferation. Finally, the introduction of exogenous c-fos in HUVSMCs induced increased protein expression levels of p-p65, COX-2, and OPN, accompanied by a remarkable increase in HUVSMC proliferation and migration. CONCLUSIONS: Our research demonstrated that hypoxia could promote the phenotypic transformation of HUVSMCs partially through the ERK1/2/c-fos/NF-κB signaling pathway, which provided a novel insight into hypoxia-associated venous wall remodeling to further aid the development of a novel therapeutic target for the prevention or treatment of VVs.

Therapeutic or prophylactic anticoagulation in acute isolated distal deep vein thrombosis: protocol for a prospective, multicentre, single-blind, randomised controlled trial (TOP-IDDVT).

INTRODUCTION: The efficacy and safety of anticoagulant treatment is not established for patients with acute symptomatic isolated distal deep vein thrombosis (IDDVT). In real-world clinical practice, both therapeutic and prophylactic anticoagulation are used for acute IDDVT. However, therapeutic anticoagulation is associated with higher risk of bleeding than prophylactic anticoagulation. Thus, this study aims to assess the efficacy and safety in patients with first acute symptomatic IDDVT treated with therapeutic or prophylactic anticoagulation using rivaroxaban. METHODS AND ANALYSIS: This study is a prospective, multicentre, single-blind, randomised controlled trial. Outpatients with a first, acute, symptomatic, objectively confirmed IDDVT in four centres from 1 August 2021 are recruited. Eligible patients are randomised in a 1:1 ratio to receive prophylactic anticoagulation (rivaroxaban 10 mg once a day for 3 months) or therapeutic anticoagulation (rivaroxaban 20 mg once a day for 3 months). All patients are followed for 6 months. The primary efficacy outcome is radiographically confirmed recurrent venous thromboembolism. The primary safety outcome is the incidence of major or clinically relevant non-major bleeding events. ETHICS AND DISSEMINATION: This study has been approved by the Ethics Committee of Zhongshan Hospital Fudan University (B2021-175R). Study results will be disseminated through peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04967573.

An Expanding Repertoire of Protein Acylations.

Protein post-translational modifications play key roles in multiple cellular processes by allowing rapid reprogramming of individual protein functions. Acylation, one of the most important post-translational modifications, is involved in different physiological activities including cell differentiation and energy metabolism. In recent years, the progression in technologies, especially the antibodies against acylation and the highly sensitive and effective mass spectrometry-based proteomics, as well as optimized functional studies, greatly deepen our understanding of protein acylation. In this review, we give a general overview of the 12 main protein acylations (formylation, acetylation, propionylation, butyrylation, malonylation, succinylation, glutarylation, palmitoylation, myristoylation, benzoylation, crotonylation, and 2-hydroxyisobutyrylation), including their substrates (histones and nonhistone proteins), regulatory enzymes (writers, readers, and erasers), biological functions (transcriptional regulation, metabolic regulation, subcellular targeting, protein-membrane interactions, protein stability, and folding), and related diseases (cancer, diabetes, heart disease, neurodegenerative disease, and viral infection), to present a complete picture of protein acylations and highlight their functional significance in future research.

Biobased polyporphyrin derived porous carbon electrodes for highly efficient capacitive deionization.

Recently, capacitive deionization (CDI) has attracted considerable interest as a potential desalination technique for seawater. It is thus desirable to develop low-cost, sustainable, and efficient electrode materials for desalination. In this study, the polyporphyrin was prepared by a one-pot reaction from biobased furan derivative, followed by activation to manufacture nitrogen-doped polyporphyrin derived porous carbons (NPPCs) for efficient capacitive deionization. In the presence of KOH as a pore activator, NPPCs exhibited cross-linked interconnected nanosphere chain-like structures inherited from the polyporphyrin backbone with coexisting mesopores and micropores, leading to extremely high specific surface area (2979.3 m2 g-1) and large pore volume (2.22 cm3 g-1). The electrochemical measurements revealed good conductivity, outstanding stability, and extraordinary specific capacitance (328.7 F g-1) of NPPCs, which can be ascribed to rich nitrogen content (8.0 at%) and high Pyrrolic nitrogen ratio. Due to their superior hierarchical porous structure and excellent electrochemical performance, the NPPC-800 electrodes presented a high salt adsorption capacity (SAC) of 35.7 mg g-1 and outstanding cycling stability in 10 mM NaCl solution at 1.2 V during the desalination tests. This work demonstrates the utilization of biobased porous carbon material will pave a prospective way in sustainable and potential applications for CDI technique.

Aortic-Related Readmission After Thoracic Endovascular Aortic Repair for Type B Aortic Dissection Patients: A Single-Center Retrospective Study.

OBJECTIVES: This study aimed to investigate the characteristics of and risk factors for aortic-related readmission after thoracic endovascular aortic repair (TEVAR) for type B aortic dissection (TBAD). METHODS: Data from TBAD patients who underwent TEVAR from 2009-2018 at a Chinese tertiary center were retrospectively collected and analyzed. Enrolled patients were categorized into 2 groups according to whether aortic-related readmission occurred during follow-up, which was defined as hospitalization at least once after the initial procedure due to events that were related to or caused by aortic dissection or the initial procedure. RESULTS: A total of 1 288 TBAD patients were enrolled, and 99 patients experienced aortic-related readmissions (7.7%), among whom chronic patients had the highest readmission rate (9.8%). The yearly proportion of readmission during the first year after initial procedure revealed a decreasing trend with a -9.7% annual percentage change. Seventy-one patients underwent reintervention (71.7%). Distal aneurysmal degeneration (43.7%) and distal stent graft-induced new entries (32.4%) were 2 major causes for reintervention. Fourteen patients in the reintervention subgroup underwent a second reintervention (19.7%). In-hospital mortality was 1.0% during the readmission and 14.3% during the second readmission. The overall survival was comparable between two groups (P = 0.93). CONCLUSIONS: This study highlighted the importance of surveillance after initial procedure for TBAD patients with potential risk factors for aortic-related readmission, and the predisposition of patients with reintervention to multiple readmissions deserves attention.