Novel STAT3 oligonucleotide compounds suppress tumor growth and overcome the acquired resistance to sorafenib in hepatocellular carcinoma.

Signal transducer and activator of transcription 3 (STAT3) plays an important role in the occurrence and progression of tumors, leading to resistance and poor prognosis. Activation of STAT3 signaling is frequently detected in hepatocellular carcinoma (HCC), but potent and less toxic STAT3 inhibitors have not been discovered. Here, based on antisense technology, we designed a series of stabilized modified antisense oligonucleotides targeting STAT3 mRNA (STAT3 ASOs). Treatment with STAT3 ASOs decreased the STAT3 mRNA and protein levels in HCC cells. STAT3 ASOs significantly inhibited the proliferation, survival, migration, and invasion of cancer cells by specifically perturbing STAT3 signaling. Treatment with STAT3 ASOs decreased the tumor burden in an HCC xenograft model. Moreover, aberrant STAT3 signaling activation is one of multiple signaling pathways involved in sorafenib resistance in HCC. STAT3 ASOs effectively sensitized resistant HCC cell lines to sorafenib in vitro and improved the inhibitory potency of sorafenib in a resistant HCC xenograft model. The developed STAT3 ASOs enrich the tools capable of targeting STAT3 and modulating STAT3 activity, serve as a promising strategy for treating HCC and other STAT3-addicted tumors, and alleviate the acquired resistance to sorafenib in HCC patients. A series of novel STAT3 antisense oligonucleotide were designed and showed potent anti-cancer efficacy in hepatocellular carcinoma in vitro and in vivo by targeting STAT3 signaling. Moreover, the selected STAT3 ASOs enhance sorafenib sensitivity in resistant cell model and xenograft model.

A self-designed liver circle for on-demand Pringle's manoeuver in laparoscopic liver resection.

BACKGROUND: Laparoscopic liver resection (LLR) allows minimal incisions and relatively quicker post-operative recovery, while intraoperative massive haemorrhage led to conversion to laparotomy. This study aimed to introduce a new, safe and convenient device to serve as Pringle's manoeuver according to the demand in LLR. METHODS: A liver circle consisting of a hole and a round stem with an obtuse small head was made by medical silica gel. It was applied in LLR to perform on-demand Pringle's manoeuver and developed its function in inferior vena cava (IVC) occlusion. The time of performing Pringle's manoeuver by liver circle, extracorporeal tourniquet and endo intestinal clip under laparoscopic simulator and LLR was compared. RESULTS: The liver circle was successfully applied to perform Pringle's manoeuver, IVC exposure and occlusion. It took less time in the occluding step of Pringle's manoeuver than the extracorporeal tourniquet (4.15 ± 0.35 s vs. 9.90 ± 1.15 s, P < 0.05) and the endo intestinal clip (4.15 ± 0.35 s vs. 47.91 ± 3.98 s, P < 0.05) under LLR. The total manipulating time for Pringle's manoeuver with liver circle remained the shortest, and the advantages were more obvious with increased frequencies of intermittent Pringle's manoeuver. CONCLUSION: The new-designed liver circle is more convenient compared to other techniques in performing Pringle's manoeuver, especially the intermittent Pringle's manoeuver in LLR. It can be used to perform on-demand hepatic blood inflow occlusion in every LLR by pre-circling the hepatoduodenal ligament to control bleeding during surgery. It can also be applied to expose the surgical field of vision and perform IVC occlusion to reduce intraoperative blood loss.

915 MHz microwave-assisted laparoscopic partial splenectomy: A case series.

BACKGROUND: Haemorrhage during the splenic parenchyma transection is a major threat for laparoscopic partial splenectomy (LPS). We here aim to evaluate the feasibility and safety of pre-coagulation of a 915 MHz microwave (MW) device during LPS. MATERIALS AND METHODS: Data of four patients admitted to our hospital between November 2016 and July 2018 were retrospectively analysed. The mean age was 24 years (range, 19-33); they all diagnosed with splenic unifocal lesion with a mean diameter of 4.6 cm (ranged from 3.7 to 6 cm) and underwent LPS with pre-coagulation of a 915 MHz MW. RESULTS: The LPS with pre-coagulation was successfully resulted in complete resection without microscopic residual tumour (R0 resection). The mean operative time was 205 min, and the minimum blood loss was at the range of 30-50 ml. No complication was observed, and the length of stay in hospital was varied from 5 to 10 days. CONCLUSION: Based on our observation, pre-coagulation of a 915 MHz MW during LPS is a safe and efficient technique. More studies are required before applying extensively.

A novel exposure maneuver in laparoscopic right hepatectomy.

BACKGROUND AND OBJECTIVES: Laparoscopic access to the posterosuperior and lateral parts of the right liver is difficult for blocked and deep surgical situations. We invented a novel water bag device (WBD) to improve the exposure of the right liver. METHODS: Eighteen consecutive patients with lesions isolated to the posterosuperior or lateral right liver were included in our research. They underwent laparoscopic right hepatectomy with the help of the device and were compared with previous similar laparoscopic cases of our operating surgeon. RESULTS: The device was successfully employed without related complications and provided enhanced and stable surgical exposure. All patients were operated on without the need for blood transfusions or laparotomy conversion. The median operation time and estimated blood loss were 227 minutes (range, 114-568) and 88 mL (range, 25-250), respectively. In all cases, tumor-free surgical margins were confirmed and no major complications were observed. The results were better than those in previous similar laparoscopic cases. CONCLUSIONS: The WBD is safe and effective for laparoscopic exposure when lesions are located in the posterosuperior and lateral parts of the right liver. With the help of the device, laparoscopic right liver resection is easier to perform instead of undergoing open hepatectomy.

Arterial resection and reconstruction in pancreatectomy: surgical technique and outcomes.

BACKGROUND: The outcomes in patients with pancreatic or ampulla tumors remain unsatisfactory, especially with invasion into the hepatic artery (HA) or the superior mesenteric artery (SMA). In this setting, pancreatectomy combined with arterial resection and reconstruction may offer the possibility of an en-block resection with negative margins and acceptable morbidity and mortality. METHODS: A six year retrospective review of pancreatectomies performed at our institution, included 21 patients that underwent a pancreatectomy combined with arterial resection and reconstruction. Arterial reconstruction was performed under an operating microscope. The types of arterial reconstruction included direct anastomosis, arterial transposition, and arterial bypass with a vascular graft. RESULTS: The surgical procedures consisted of 19 pancreaticoduodenectomies and 2 total pancreatectomies. The tumors were located at the pancreatic head (n = 10), whole pancreas (n = 2), distal common bile duct (n = 5), ampulla (n = 2) and retroperitoneum with pancreatic head involvement (n = 2). All operations achieved R0 resection successfully, with no intraoperative complication. Eighteen patients recovered without complications while three patients died from intra-abdominal hemorrhage due to a pancreatic fistula, though notably the bleeding was not at the arterial anastomosis site. All reconstructed arteries showed adequate patency at follow-up. The median postoperative survival was 11.6 months in all the 11 patients with pancreatic adenocarcinoma. CONCLUSION: Pancreatectomy combined with arterial resection and reconstruction is a feasible treatment option. The microsurgical technique is critically important to achieving a successful and patent arterial anastomosis.

Chirality-specific lift forces of helix under shear flows: Helix perpendicular to shear plane.

Chiral objects in shear flow experience a chirality-specific lift force. Shear flows past helices in a low Reynolds number regime were studied using slender-body theory. The chirality-specific lift forces in the vorticity direction experienced by helices are dominated by a set of helix geometry parameters: helix radius, pitch length, number of turns, and helix phase angle. Its analytical formula is given. The chirality-specific forces are the physical reasons for the chiral separation of helices in shear flow. Our results are well supported by the latest experimental observations.

Primary abdominal lymphangioleiomyomatosis: report of a case.

Lymphangioleiomyomatosis is an uncommon progressive disease characterized by hamartomatous smooth muscle proliferation of the airways within the lungs as well as the lymph nodes, lymphatics, and blood vessels of the lungs, mediastinum, and abdomen. The most common manifestations of lymphangioleiomyomatosis are pulmonary symptoms. Primary abdominal lymphangioleiomyomatosis without any pathological changes in the respiratory system is extremely unusual. We report a case of primary abdominal lymphangioleiomyomatosis located between the left hepatic and gastric antrum of a 29-year-old woman. The patient had no typical symptoms of lymphangioleiomyomatosis (dyspnea, pneumothorax) or abdominal pain. All physical examination findings were normal. Laboratory test results, including routine blood examination, liver and kidney function, tumor markers, blood coagulation function, and urine and stool examinations, were all normal. She found abdominal cyst in an annual medical examination by ultrasonography and confirmed by computed tomography. For a clear diagnosis, a laparoscopic abdominal mass resection was performed. The postoperative pathohistological examination findings allowed for the definitive diagnosis. This case report may advance the understanding of primary peritoneal lymphatic leiomyoma and reduce the number of mistakenly diagnosed patients.

Ischemic preconditioning improves liver tolerance to congestion-reperfusion injury in mice.

BACKGROUND: Congestion-reperfusion injury (CRI) is a common complication after living donor liver transplantation, which has not been fully understood. It causes more severe inflammatory response as compared with ischemia-reperfusion injury (IRI). Ischemic preconditioning (IPC) has been endowed with powerful protective properties toward IRI. This study aimed to investigate whether IPC also has a protective effect against CRI and potential underlying mechanisms. MATERIALS AND METHODS: Mice were randomly divided into sham operation, CRI, IPC-CRI, and congestion precondition (CPC-CRI) group. The hepatic vein of the left anterior hepatic lobe was occluded for 75 min followed by reperfusion in the CRI group. The blood inflow was previously clamped for 10 min followed by 10 min of reperfusion just before occluding the hepatic vein in the IPC-CRI group. To imitating IPC in the CPC-CRI group, 10 min of congestion followed by 10 min of reperfusion just before CRI was performed. The animals were sacrificed at 2, 6, 24, 48 h, and 7 d after reperfusion. The blood and liver samples were collected for hepatic function assay, histology, terminal deoxynucleotidyl transferase dUTP nick end labeling, myeloperoxidase, and real-time polymerase chain reaction analysis. RESULTS: Mice in the CRI, IPC-CRI, and CPC-CRI group demonstrated elevated liver enzymes, histologic damage, cellular apoptosis, and inflammatory response compared with those in the sham operation group. Compared with the CRI group, mice in the IPC-CRI group expressed lower alanine transaminase activities (2 h: 839.2 ± 132.5 versus 384.2 ± 94.8, P < 0.01; and 6 h: 680 ± 142.4 versus 342.3 ± 99.7, P < 0.01) and lower myeloperoxidase levels (2 h: 7.1 ± 4.0 U/g versus 3.8 ± 1.6 U/g, P < 0.05; and 6 h: 8.1 ± 1.3 U/g versus 5.2 ± 3.0 U/g, P < 0.05). However, the alanine transaminase level in the CPC-CRI group was notably higher at 2 h (839.2 ± 132.5 versus 1087.5 ± 192.5, P < 0.05). Livers from mice in the IPC-CRI group showed better tissue integrity, diminished hepatocellular injury, and apoptosis at 2 and 6 h. The messenger RNA transcriptions of interleukin 1 and interleukin 6 were significantly lower after 2-24 h of reperfusion, whereas tumor necrosis factor α and monocyte chemoattractant protein 1 were significantly lower after 24 h of reperfusion in the IPC-CRI group. CONCLUSIONS: IPC can significantly improve liver tolerance to CRI by attenuating neutrophil infiltration, proinflammatory cytokine formation, and hepatocytes apoptosis. This pretreatment strategy holds greater prospect of being translated into clinical use in living donor liver transplantation.

Advanced tissue engineering scaffold design for regeneration of the complex hierarchical periodontal structure.

AIM: This study investigated the ability of an osteoconductive biphasic scaffold to simultaneously regenerate alveolar bone, periodontal ligament and cementum. MATERIALS AND METHODS: A biphasic scaffold was built by attaching a fused deposition modelled bone compartment to a melt electrospun periodontal compartment. The bone compartment was coated with a calcium phosphate (CaP) layer for increasing osteoconductivity, seeded with osteoblasts and cultured in vitro for 6 weeks. The resulting constructs were then complemented with the placement of PDL cell sheets on the periodontal compartment, attached to a dentin block and subcutaneously implanted into athymic rats for 8 weeks. Scanning electron microscopy, X-ray diffraction, alkaline phosphatase and DNA content quantification, confocal laser microscopy, micro computerized tomography and histological analysis were employed to evaluate the scaffold's performance. RESULTS: The in vitro study showed that alkaline phosphatase activity was significantly increased in the CaP-coated samples and they also displayed enhanced mineralization. In the in vivo study, significantly more bone formation was observed in the coated scaffolds. Histological analysis revealed that the large pore size of the periodontal compartment permitted vascularization of the cell sheets, and periodontal attachment was achieved at the dentin interface. CONCLUSIONS: This work demonstrates that the combination of cell sheet technology together with an osteoconductive biphasic scaffold could be utilized to address the limitations of current periodontal regeneration techniques.

A Bioactive Degradable Composite Bone Cement Based on Calcium Sulfate and Magnesium Polyphosphate.

Calcium sulfate bone cement (CSC) is extensively used as a bone repair material due to its ability to self-solidify, degradability, and osteogenic ability. However, the fast degradation, low mechanical strength, and insufficient biological activity limit its application. This study used magnesium polyphosphate (MPP) and constructed a composite bone cement composed of calcium sulfate (CS), MPP, tricalcium silicate (C3S), and plasticizer hydroxypropyl methylcellulose (HPMC). The optimized CS/MPP/C3S composite bone cement has a suitable setting time of approximately 15.0 min, a compressive strength of 26.6 MPa, and an injectability of about 93%. The CS/MPP/C3S composite bone cement has excellent biocompatibility and osteogenic capabilities; our results showed that cell proliferation is up to 114% compared with the control after 5 days. After 14 days, the expression levels of osteogenic-related genes, including Runx2, BMP2, OCN, OPN, and COL-1, are about 1.8, 2.8, 2.5, 2.2, and 2.2 times higher than those of the control, respectively, while the alkaline phosphatase activity is about 1.7 times higher. Therefore, the CS/MPP/C3S composite bone cement overcomes the limitations of CSC and has more effective potential in bone repair.

An outlier removal method based on PCA-DBSCAN for blood-SERS data analysis.

Surface-enhanced Raman spectroscopy (SERS) has shown promising potential in cancer screening. In practical applications, Raman spectra are often affected by deviations from the spectrometer, changes in measurement environments, and anomalies in spectrum characteristic peak intensities due to improper sample storage. Previous research has overlooked the presence of outliers in categorical data, leading to significant impacts on model learning outcomes. In this study, we propose a novel method, called Principal Component Analysis and Density Based Spatial Clustering of Applications with Noise (PCA-DBSCAN) to effectively remove outliers. This method employs dimensionality reduction and spectral data clustering to identify and remove outliers. The PCA-DBSCAN method introduces adjustable parameters (Eps and MinPts) to control the clustering effect. The effectiveness of the proposed PCA-DBSCAN method is verified through modeling on outlier-removed datasets. Further refinement of the machine learning model and PCA-DBSCAN parameters resulted in the best cancer screening model, achieving 97.41% macro-average recall and 97.74% macro-average F1-score. This paper introduces a new outlier removal method that significantly improves the performance of the SERS cancer screening model. Moreover, the proposed method serves as inspiration for outlier detection in other fields, such as biomedical research, environmental monitoring, manufacturing, quality control, and hazard prediction.

CuSO4/H2O2induced polydopamine/polysulfobetaine methacrylate co-deposition on poly(amino acid) membranes for improved anti-protein adsorption and antibacterial activity.

Stopping postoperative soft tissue adhesions is one of the most challenging clinical problems that needs to be addressed urgently to avoid secondary injury and pain to patients. Currently, membrane materials with anti-protein adsorption and antibacterial activity are recognized as an effective and promising anti-adhesion barrier to prevent postoperative adhesion and the recurrent adhesion after adhesiolysis. Herein, poly(amino acid) (PAA), which is structurally similar to collagen, is selected as the membrane base material to successfully synthesize PAA-5 membranes with excellent mechanical and degradation properties by in-situ melt polymerization and hot-melt film-forming technology. Subsequently, the co-deposition of polydopamine/polysulfobetaine methacrylate (PDA/PSBMA) coatings induced by CuSO4/H2O2on PAA-5 membranes results in the formation of PDC-5S and PDC-10S, which exhibit excellent hemocompatibility, protein antifouling properties, and cytocompatibility. Additionally, PDC-5S and PDC-10S demonstrated significant antibacterial activity againstEscherichia coliandStaphylococcus aureus, with an inhibition rate of more than 90%. As a result, this study sheds light on newly discovered PAA membranes with anti-protein adsorption and antibacterial activity can sever as one of the promising candidates for the prevention of postoperative peritoneum adhesions.

Non-invasive screening and subtyping for breast cancer by serum SERS combined with LGB-DNN algorithms.

Early detection of breast cancer and its molecular subtyping is crucial for guiding clinical treatment and improving survival rate. Current diagnostic methods for breast cancer are invasive, time consuming and complicated. In this work, an optical detection method integrating surface-enhanced Raman spectroscopy (SERS) technology with feature selection and deep learning algorithm was developed for identifying serum components and building diagnostic model, with the aim of efficient and accurate noninvasive screening of breast cancer. First, the high quality of serum SERS spectra from breast cancer (BC), breast benign disease (BBD) patients and healthy controls (HC) were obtained. Chi-square tests were conducted to exclude confounding factors, enhancing the reliability of the study. Then, LightGBM (LGB) algorithm was used as the base model to retain useful features to significantly improve classification performance. The DNN algorithm was trained through backpropagation, adjusting the weights and biases between neurons to improve the network's predictive ability. In comparison to traditional machine learning algorithms, this method provided more accurate information for breast cancer classification, with classification accuracies of 91.38 % for BC and BBD, and 96.40 % for BC, BBD, and HC. Furthermore, the accuracies of 90.11 % for HR+/HR- and 88.89 % for HER2+/HER2- can be reached when evaluating BC patients' molecular subtypes. These results demonstrate that serum SERS combined with powerful LGB-DNN algorithm would provide a supplementary method for clinical breast cancer screening.

The MyD88 inhibitor, ST2825, induces cell cycle arrest and apoptosis by suppressing the activation of the NF­κB/AKT1/p21 pathway in pancreatic cancer.

NF­κB activation occurs in the majority patients with pancreatic ductal adenocarcinoma (PDAC); however, directly targeting NF­κB has proven unsuccessful, and recent studies have demonstrated a certain effect of the indirect inhibition of NF­κB. Myeloid differentiation factor 88 (MyD88) is a common intermediate messenger for NF­κB activation by inducers. In the present study, the level of MyD88 in PDAC was detected using a public database and a tissue chip. A specific inhibitor (ST2825) of MyD88 was used on PDAC cell lines. Flow cytometry was used to examine apoptosis and cell cycle progression. Transcriptome sequencing was used for ST2825­treated PANC­1 cells compared with untreated PANC­1 cells. The levels of related factors were measured using reverse transcription­quantitative PCR and western blot analysis. Chromatin immunoprecipitation, co­immunoprecipitation, transcription factor assay and an NF­κB phospho­antibody array were performed to identify the detailed underlying mechanisms. Animal experiments were performed to verify the effects of ST2825 on PDAC, which were found in the in vitro experiments. MyD88 was found to be overexpressed in PDAC. ST2825 induced the G2/M phase cell cycle arrest and apoptosis of PDAC cells. ST2825 inhibited MyD88 dimerization to inactivate the NF­κB pathway. ST2825 inhibited AKT1 expression and induced p21 overexpression to induce G2/M phase cell cycle arrest and apoptosis by inhibiting NF­κB transcriptional activity. NF­κB activation, AKT1 overexpression or p21 knockdown partially reversed the effects of ST2825 in PDAC. On the whole, the findings of the present study demonstrate that ST2825 induces G2/M cell cycle arrest and apoptosis via the MyD88/NF­κB/AKT1/p21 pathway in PDAC. MyD88 may thus serve as a potential therapeutic target in PDAC. ST2825 may serve as a novel agent for the targeted therapy of PDAC in the future.

Fabricating biodegradable calcium phosphate/calcium sulfate cement reinforced with cellulose: in vitro and in vivo studies.

Osteoporosis is a growing public health concern worldwide. To avoid extra surgeries, developing biodegradable bone cement is critical for the treatment of osteoporosis. Herein, we designed calcium phosphate/calcium sulfate cement reinforced with sodium carboxymethyl cellulose (CMC/OPC). It presents an appropriate physicochemical performance for clinical handling. Meanwhile, CMC/OPC bone cement promotes osteogenic differentiation in vitro. Results of the immune response in vitro and in vivo confirmed that increasing the cellulose content triggered macrophage switching into the M2 phenotype and CMC/OPC exhibited significant anti-inflammation. Furthermore, in vitro and in vivo degradation demonstrated that cellulose tailors the degradation rate of composite bone cement, which achieved a linear degradation process and could degrade by more than 90% for 12 weeks. In summary, the composite bone cement CMC/OPC is a promising candidate for bone repair applications.

Effects of ATP on the Physicochemical Properties and Cytocompatibility of Calcium Sulfate/Calcium Citrate Composite Cement.

Adenosine triphosphate (ATP), acting as a source of energy, has effects on cellular activities, such as adhesion, proliferation, and differentiation. In this study, ATP-loaded calcium sulfate hemihydrate/calcium citrate tetrahydrate cement (ATP/CSH/CCT) was successfully prepared for the first time. The effect of different contents of ATP on the structure and physicochemical properties of ATP/CSH/CCT was also studied in detail. The results indicated that incorporating ATP into the cement did not significantly alter their structures. However, the addition ratio of ATP directly impacted the mechanical properties and in vitro degradation properties of the composite bone cement. The compressive strength of ATP/CSH/CCT gradually decreased with an increasing ATP content. The degradation rate of ATP/CSH/CCT did not significantly change at low concentrations of ATP, but it increased with a higher ATP content. The composite cement induced the deposition of a Ca-P layer in a phosphate buffer solution (PBS, pH = 7.4). Additionally, the release of ATP from the composite cement was controlled. The ATP was controlled releasing at the 0.5% and 1% ATP in cement by the diffusion of ATP and the degradation of the cement, whereas it was controlled by the diffusion process merely at the 0.1% ATP in cement. Furthermore, ATP/CSH/CCT demonstrated good cytoactivity with the addition of ATP and is expected to be used for the repair and regeneration of bone tissue.

Laser tweezer Raman spectroscopy combined with deep neural networks for identification of liver cancer cells.

Rapid identification of cancer cells is crucial for clinical treatment guidance. Laser tweezer Raman spectroscopy (LTRS) that provides biochemical characteristics of cells can be used to identify cell phenotypes through classification models in a non-invasive and label-free manner. However, traditional classification methods require extensive reference databases and clinical experience, which is challenging when sampling at inaccessible locations. Here, we describe a classification method combing LTRS with deep neural network (DNN) for differential and discriminative analysis of multiple liver cancer (LC) cells. By using LTRS, we obtained high-quality single-cell Raman spectra of normal hepatocytes (HL-7702) and liver cancer cell lines (SMMC-7721, Hep3B, HepG2, SK-Hep1 and Huh7). The tentative assignment of Raman peaks indicated that arginine content was elevated and phenylalanine, glutathione and glutamate content was decreased in liver cancer cells. Subsequently, we randomly selected 300 spectra from each cell line for DNN model analysis, achieving a mean accuracy of 99.2%, a mean sensitivity of 99.2% and a mean specificity of 99.8% for the identification and classification of multiple LC cells and hepatocyte cells. These results demonstrate the combination of LTRS and DNN is a promising method for rapid and accurate cancer cell identification at single cell level.

Targeting STAT3-VISTA axis to suppress tumor aggression and burden in acute myeloid leukemia.

The acute myeloid leukemia (AML) patients obtain limited benefits from current immune checkpoint blockades (ICBs), although immunotherapy have achieved encouraging success in numerous cancers. Here, we found that V-domain Ig suppressor of T cell activation (VISTA), a novel immune checkpoint, is highly expressed in primary AML cells and associated with poor prognosis of AML patients. Targeting VISTA by anti-VISTA mAb boosts T cell-mediated cytotoxicity to AML cells. Interestingly, high expression of VISTA is positively associated with hyperactive STAT3 in AML. Further evidence showed that STAT3 functions as a transcriptional regulator to modulate VISTA expression by directly binding to DNA response element of VISTA gene. We further develop a potent and selective STAT3 inhibitor W1046, which significantly suppresses AML proliferation and survival. W1046 remarkably enhances the efficacy of VISTA mAb by activating T cells via inhibition of STAT3 signaling and down-regulation of VISTA. Moreover, combination of W1046 and VISTA mAb achieves a significant anti-AML effect in vitro and in vivo. Overall, our findings confirm that VISTA is a potential target for AML therapy which transcriptionally regulated by STAT3 and provide a promising therapeutic strategy for immunotherapy of AML.

Oxidation and polymer degradation characteristics of high viscosity modified asphalts under various aging environments.

High viscosity modified asphalt (HVMA) was the core material to build ecological permeable pavement, while it was prone to aging, which limited its applications for urban sustainability. This study focused on the oxidation and polymer degradation characteristics of the high-content styrene-butadiene-styrene modified asphalt, high-viscosity composite particle modified asphalt and high-elastic modified asphalt under the simulated aging environments of thermal oxidation and weather. Gel permeation chromatography results showed that the increase percent of large molecular size percent and the decrease percent of polymer weight could characterize the oxidation degree and polymer degradation degree, respectively. The degrees of oxidation and polymer degradation in all HVMAs increased synchronously with aging, and reached the highest after the weather aging. The polymer molecular distribution of HVMA would become more uniform with aging from the proposed ratio of polymer weight to polymer content. Dynamic shear rheometer tests reflected that there existed the dual effects of coupling and parallelism during aging of HVMA, i.e. the oxidation-induced hardening effect and degradation-induced softening effect. Furthermore, the change percent of rheological indicators was proposed as the net aging degree. Considering the rheological properties of aged HVMA were the coupling results of dual effects, the net aging degree could represent the oxidation dominance degree or polymer degradation dominance degree of HVMA. Due to the differences of dual effects and polymer molecular distribution, various HVMAs showed the totally different net aging degree ranking, depending on the aging states and rheological indicators. Notably, the high-elastic modified asphalt showed the greatest aging resistance at all aging states as a result of its weak dual effects and most uniform polymer molecular distribution.

Arg-Gly-Asp peptide functionalized poly-amino acid/ poly (p-benzamide) copolymer with enhanced mechanical properties and osteogenicity.

Poly-amino acid (PAA) is a promising biomaterial in biomedical engineering due to its similar amide bond structure to collagen and excellent biocompatibility, but the lack of osteogenic activity and inferior mechanical strength limit its long-term application in orthopedics. In this study, a poly-amino acid/poly (p-benzamide) (PAA-PBA) copolymer with high mechanical strength was designed and fabricated by the method of solution polymerization. The chain structures, thermal properties and mechanical properties of these polymers were evaluated and results showed that PBA greatly promoted the mechanical properties of PAA, and the copolymer performed the maximum mechanical strengths with compressive strength, bending strength and tensile strength of 123 MPa, 107 MPa and, 95 MPa, respectively. To increase the bioactivity of surface, a bioactive coating that consists of poly-(dopamine) (PDA) nanolayers and tripeptide Arginine-Glycine-Aspartic acid (RGD) on sulfonated PAA-PBA copolymer was created. A porous structure appeared on the surface after modification, the surface roughness and hydrophilicity of copolymer has been improved obviously after introducing PDA and RGD peptide coating. The in vitro bioactivity evaluation demonstrated that the RGD-functionalized sample showed a significantly improved ability to promote bone apatite mineralization, cell adhesion, proliferation and osteogenic differentiation. In a word, such a strategy of material synthesis and surface modification method shows a great potential for broadening the use of PAA in the application of load-bearing bone substitute biomaterials.