Biomineralized tetramethylpyrazine-loaded PCL/gelatin nanofibrous membrane promotes vascularization and bone regeneration of rat cranium defects.

Conventional electrospinning produces nanofibers with smooth surfaces that limit biomineralization ability. To overcome this disadvantage, we fabricated a tetramethylpyrazine (TMP)-loaded matrix-mimicking biomineralization in PCL/Gelatin composite electrospun membranes with bubble-shaped nanofibrous structures. PCL/Gelatin membranes (PG), PCL/Gelatin membranes containing biomineralized hydroxyapatite (HA) (PGH), and PCL/Gelatin membranes containing biomineralized HA and loaded TMP (PGHT) were tested. In vitro results indicated that the bubble-shaped nanofibrous surface increased the surface roughness of the nanofibers and promoted mineralization. Furthermore, sustained-release TMP had an excellent drug release efficiency. Initially released vigorously, it reached stabilization at day 7, and the slow-release rate stabilized at 61.0 ± 1.8% at 28 days. All membranes revealed an intact cytoskeleton, cell viability, and superior adhesion and proliferation when stained with Ghost Pen Cyclic Peptide, CCK-8, cell adhesion, and EdU. In PGHT membranes, the osteogenic and vascularized gene expression of BMSCs and human vascular endothelial cells was significantly upregulated compared with that in other groups, indicating the PGHT membranes exhibited an effective vascularization role. Subsequently, the membranes were implanted in a rat cranium defect model for 4 and 8 weeks. Micro-CT and histological analysis results showed that the PGHT membranes had better bone regenerative patterns. Additionally, the levels of CD31 and VEGF significantly increased in the PGHT membrane compared with those in other membranes. Thus, PGHT membranes could accelerate the repair of cranium defects in vivo via HA and TMP synergistic effects.

Outcomes of Drug-Coated Balloon Angioplasty for Isolated Chronic Occlusion of the Popliteal Artery: A Retrospective Single-Institution Study.

PURPOSE: To assess the 12-month safety and effectiveness of paclitaxel drug-coated balloon (DCB) for the treatment of patients with isolated chronic occlusions in popliteal arteries and evaluate the risk factors of lesion reocclusion. MATERIALS AND METHODS: From January 2018 to December 2019, DCB angioplasty was performed in 54 limbs with isolated chronic popliteal artery occlusion of 48 patients (32 men) with a mean age of 71.5 ± 12.1 (range, 50-97) years, mean occlusive length of 6.3 ± 3.0 (range, 1-15) cm, and mean preoperative ankle-brachial index (ABI) of 0.42 ± 0.12 (range, 0.19-0.58). A total of 18.5% (10/54) of lesions were long-segment occlusions involving the entire popliteal artery from P1 to P3. Twenty seven of 54 limbs presented with critical limb ischemia (CLI) with a mean ABI of 0.33 ± 0.10 (range, 0.19-0.51). The primary endpoint was primary patency rate at 12 months. The secondary endpoints included technical success rate, 1-year secondary patency rate, limb salvage rate, and improvement in clinical symptoms. Univariate Cox regression analysis was used to determine the predictors of lesion reocclusion. RESULTS: The technical success rate was 85.2% (46/54), and bailout stenting was performed in 14.8% (8/54) of lesions. The 12-month primary and secondary patency rates by the Kaplan-Meier estimate were 72.6% and 88.3%, respectively. Two thirds of the reocclusions occurred within 6 months after intervention. No 30-day mortality was observed. The limb salvage rate was 100% during a mean follow-up period of 13 months, and all minor amputations occurred in the limbs presented with CLI. The mean ABI increased from 0.42 before the procedure to 0.73 after the procedure. Patients younger than 60 years and the lesions exhibiting long-segment occlusions present as trending risk factors for lesion reocclusion. CONCLUSIONS: Paclitaxel DCB angioplasty is safe and effective in managing isolated chronic occlusion of popliteal arteries. Younger patients and long-segment occlusions of the popliteal artery are associated with a relatively higher reocclusion rate after the procedure.

Epigallocatechin-3-Gallate-Loaded Liposomes Favor Anti-Inflammation of Microglia Cells and Promote Neuroprotection.

Microglia-mediated neuroinflammation is recognized to mainly contribute to the progression of neurodegenerative diseases. Epigallocatechin-3-gallate (EGCG), known as a natural antioxidant in green tea, can inhibit microglia-mediated inflammation and protect neurons but has disadvantages such as high instability and low bioavailability. We developed an EGCG liposomal formulation to improve its bioavailability and evaluated the neuroprotective activity in in vitro and in vivo neuroinflammation models. EGCG-loaded liposomes have been prepared from phosphatidylcholine (PC) or phosphatidylserine (PS) coated with or without vitamin E (VE) by hydration and membrane extrusion method. The anti-inflammatory effect has been evaluated against lipopolysaccharide (LPS)-induced BV-2 microglial cells activation and the inflammation in the substantia nigra of Sprague Dawley rats. In the cellular inflammation model, murine BV-2 microglial cells changed their morphology from normal spheroid to activated spindle shape after 24 h of induction of LPS. In the in vitro free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, EGCG scavenged 80% of DPPH within 3 min. EGCG-loaded liposomes could be phagocytized by BV-2 cells after 1 h of cell culture from cell uptake experiments. EGCG-loaded liposomes improved the production of BV-2 microglia-derived nitric oxide and TNF-α following LPS. In the in vivo Parkinsonian syndrome rat model, simultaneous intra-nigral injection of EGCG-loaded liposomes attenuated LPS-induced pro-inflammatory cytokines and restored motor impairment. We demonstrated that EGCG-loaded liposomes exert a neuroprotective effect by modulating microglia activation. EGCG extracted from green tea and loaded liposomes could be a valuable candidate for disease-modifying therapy for Parkinson's disease (PD).

Backbone Structure Effect on the Thermoelectric Properties of IDT-Based p-Type Conjugated Polymers.

Four conjugated polymers are synthesized through indacenodithiohene (IDT) unit copolymerized with thiophene and thiophene derivatives. Indacenodithiohene-co-thieno[3,2-b]thiophene (IDT-TT) and indacenodithiohene-co-trans-1,2-di(2-thienyl)ethylene (IDT-TVT) exhibit better charge transport mobilities than indacenodithiohene-co-thiophene (IDT-T) and indacenodithiohene-co-3,4-ethoxylene dioxythiophene (IDT-EDOT), and also display superior thermoelectric properties after doping. Theoretical calculations suggest that IDT-EDOT and IDT-TVT have better coplanarities; the inferior performance for IDT-EDOT might be due to its low molecular weight. Meanwhile, it is worth mentioning that via the synergistic effect of two dopants (CN6CP, CuTFSI), the electrical conductivities of the polymers are further improved. The XPS data shows that the coordination interaction between copper ion and the cyano groups of CN6CP introduces cupric ions into the polymer films, which leads to the increase of the doping ratio.

Coaxial Electrospun Polycaprolactone/Gelatin Nanofiber Membrane Loaded with Salidroside and Cryptotanshinone Synergistically Promotes Vascularization and Osteogenesis.

Background: Salidroside (SAL) is the most effective component of Rhodiola rosea, a traditional Chinese medicine. Cryptotanshinone (CT) is the main fat-soluble extract of Salvia miltiorrhiza, exhibiting considerable potential for application in osteogenesis. Herein, a polycaprolactone/gelatin nanofiber membrane loaded with CT and SAL (PSGC membrane) was successfully fabricated via coaxial electrospinning and characterized. Methods and Results: This membrane capable of sustained and controlled drug release was employed in this study. Co-culturing the membrane with bone marrow mesenchymal stem cells and human umbilical vein endothelial cells revealed excellent biocompatibility and demonstrated osteogenic and angiogenic capabilities. Furthermore, drug release from the PSGC membrane activated the Wnt/ß-catenin signaling pathway and promoted osteogenic differentiation and vascularization. Evaluation of the membrane's vascularization and osteogenic capacities involved transplantation onto a rat's subcutaneous area and assessing rat cranium defects for bone regeneration, respectively. Microcomputed tomography, histological tests, immunohistochemistry, and immunofluorescence staining confirmed the membrane's outstanding angiogenic capacity two weeks post-operation, with a higher incidence of osteogenesis observed in rat cranial defects eight weeks post-surgery. Conclusion: Overall, the SAL- and CT-loaded coaxial electrospun nanofiber membrane synergistically enhances bone repair and regeneration.

The ASB@HNTs-PVA nanofiber membrane, possessing both anti-inflammatory and hemostatic activities, promotes the healing of T2D skin wounds.

The healing of diabetic wounds has long been a significant challenge in the field of medicine. The elevated sugar levels surrounding diabetic wounds create a conducive environment for harmful bacterial growth, resulting in purulent infections that impede the healing process. Thus, the development of a biomaterial that can enhance the healing of diabetic wounds holds great importance. This study developed electrospun dressings for wound healing by combining traditional Chinese medicine and clay. The study utilized electrospinning technology to prepare polyvinyl alcohol (PVA) nanofiber membranes containing ASB and HNTs. These ASB@HNTs-PVA nanofiber membranes demonstrated rapid hemostasis, along with antibacterial and anti-inflammatory properties, facilitating the recovery of type 2 diabetic (T2D) wounds. Various analyses were conducted to assess the performance of the composite nanofiber membrane, including investigations into its biocompatibility and hemostatic abilities through antibacterial experiments, cell experiments, and mouse liver tail bleeding experiments. Western blot analysis confirmed that the composite nanofiber membrane could decrease the levels of inflammatory factors IL-1ß and TNF-α. A type 2 diabetic mouse model was utilized, with wounds artificially induced on the backs of mice. Application of the nanofiber membrane to the wounds further confirmed its anti-inflammatory effects and ability to enhance wound healing in vivo.

A Laparoscopically Compatible Rapid-Adhesion Bioadhesive for Asymmetric Adhesion, Non-Pressing Hemostasis, and Seamless Seal.

Bioadhesive hydrogels offer unprecedented opportunities in hemostatic agents and tissue sealing; however, the application of existing bioadhesive hydrogels through narrow spaces to achieve strong adhesion in fluid-rich physiological environments is challenged either by undesired indiscriminate adhesion or weak wet tissue adhesion. Here, a laparoscopically compatible asymmetric adhesive hydrogel (aAH) composed of sprayable adhesive hydrogel powders and injectable anti-adhesive glue is proposed for hemostasis and to seal the bloody tissues in a non-pressing way, allowing for preventing postoperative adhesion. The powders can seed on the irregular bloody wound to rapidly absorb interfacial fluid, crosslink, and form an adhesive hydrogel to hemostatic seal (blood clotting time and tissue sealing in 10 s, ≈200 mm Hg of burst pressure in sealed porcine tissues). The aAH can be simply formed by crosslinking the upper powder with injectable glue to prevent postoperative adhesion (adhesive strength as low as 1 kPa). The aAH outperforms commercial hemostatic agents and sealants in the sealing of bleeding organs in live rats, demonstrating superior anti-adhesive efficiency. Further, the hemostatic seamless sealing by aAH succeeds in shortening the time of warm ischemia, decreasing the blood loss, and reducing the possibility of rebleeding in the porcine laparoscopic partial nephrectomy model.

Application of the New Irrigation Protocol to Reduce Recurrence Rate in the Management Of Periprosthetic Joint Infection.

OBJECTIVE: Irrigation is a conventional treatment for acute and chronic periprosthetic joint infections (PJI). However, there has been no unified standard for irrigation during surgery for PJI in the past, and the efficacy is uncertain. The purpose of this study is to create a new irrigation protocol to enhance the infection control rate and reduce the postoperative recurrence rate of PJI patients. METHODS: We conducted a single-institution retrospective review with a total of 56 patients who underwent revision total hip or knee arthroplasties due to PJI from January 2011 to January 2022. Conventional irrigation (CI) was used in 32 cases, and standard operating procedure of irrigation (SOPI) was used in 24. The CI protocol carries out an empirical irrigation after debridement, which is quite random. Our SOPI protocol clearly stipulates the soaking concentration and time of hydrogen peroxide and povidone-iodine. The irrigation is carried out three times, and tissue samples are taken from multiple parts before and after irrigation, which are sent for microbial culture. The important statistical indicators were the rate of positive microbiological culture and postoperative recurrence rate with an average follow-up of 24 average months. RESULTS: The drainage volume was lower in the SOPI group than in the CI group on postoperative day 3 (p < 0.01) and 7 (p = 0.016). In addition, the percentage of positive microbiological cultures after the third irrigation was less than that before (p < 0.01) and after (p < 0.01) the first irrigation. The most common causative organism was Staphylococcus aureus, which was detected in 25.0% and 12.5% of the SOPI and CI groups, respectively. The failure rate at the final follow-up was 8.3% and 31.3% (p = 0.039) for the SOPI and CI groups, respectively. CONCLUSION: Compared with the traditional CI method, SOPI standardized the soaking time of hydrogen peroxide and povidone-iodine, increased the frequency of and irrigation, and proved that microorganisms were almost completely removed through the microbial culture of multiple tissues. SOPI has the potential to become a standardized irrigation process worthy of promotion, effectively reducing the postoperative recurrence rate of PJI patients.

Fabrication of a three-dimensional printed gelatin/sodium alginate/nano-attapulgite composite polymer scaffold loaded with leonurine hydrochloride and its effects on osteogenesis and vascularization.

Bone tissue engineering scaffolds have made significant progress in treating bone defects in recent decades. However, the lack of a vascular network within the scaffold limits bone formation after implantation in vivo. Recent research suggests that leonurine hydrochloride (LH) can promote healing in full-thickness cutaneous wounds by increasing vessel formation and collagen deposition. Gelatin and Sodium Alginate are both polymers. ATP is a magnesium silicate chain mineral. In this study, a Gelatin/Sodium Alginate/Nano-Attapulgite composite hydrogel was used as the base material first, and the Gelatin/Sodium Alginate/Nano-Attapulgite composite polymer scaffold loaded with LH was then created using 3D printing technology. Finally, LH was grafted onto the base material by an amide reaction to construct a scaffold loaded with LH to achieve long-term LH release. When compared to pure polymer scaffolds, in vitro results showed that LH-loaded scaffolds promoted the differentiation of BMSCs into osteoblasts, as evidenced by increased expression of osteogenic key genes. The results of in vivo tissue staining revealed that the drug-loaded scaffold promoted both angiogenesis and bone formation. Collectively, these findings suggest that LH-loaded Gelatin/Sodium Alginate/Nano-Attapulgite composite hydrogel scaffolds are a potential therapeutic strategy and can assist bone regeneration.

Polycaprolactone/Gelatin/Hydroxyapatite Electrospun Nanomembrane Materials Incorporated with Different Proportions of Attapulgite Synergistically Promote Bone Formation.

Purpose: To enhance the osteoinductive effect of Hydroxyapatite (HA) in bone tissue engineering, this study manufactured polycaprolactone (PCL)/gelatin (GEL)/HA nanofibrous scaffolds incorporated with different ratios of attapulgite (ATP): HA (0:3, 0:0, 1:1, 2:1 and 3:0) by high-voltage electrospinning. The synergistic effect exerted by ATP and HA on bone formation was explored both in vivo and in vitro. Methods and Results: First, we determined the group composition and crystal structure of the nanosheets by Fourier transform infrared (FTIR) and X-ray diffraction (XRD) analyses. Then, the physical properties of the scaffolds, including the modulus of elasticity, porosity and water absorption were evaluated. Moreover, the surface microstructure of the nanofibrous scaffolds was captured by Scanning electron microscopy (SEM) and Transmission Electron Microscope (TEM). The biocompatibility of the fabricated scaffolds represented by cell counting kit 8 (CCK-8) and phalloidin staining was also assessed. Next, in vitro osteogenesis was evaluated. Real-time PCR, alkaline phosphatase (ALP) staining and Alizarin red S (ARS) staining results showed that the materials incorporated with HA and ATP at a ratio of 2:1 synergistically promoted more osteoblastic differentiation and extracellular mineralization than scaffolds doped with HA and ATP alone. Last, in vivo, Hematoxylin-Eosin staining (HE staining) and Masson staining showed that groups treated with HA and ATP acquired optimal patterns of bone regeneration. Conclusion: This study clarified for the first time that the combination of HA and ATP orchestrated biomaterial-induced osseointegration, and the synergistic effect was more significant when the ratio of ATP/HA was 2:1. This conclusion also provides new ideas and a scientific basis for the development of functionalized nanomaterials in bone tissue engineering.

Impaction Bone Grafting Combined with Titanium Mesh for Acetabular Bone Defects Reconstruction in Total Hip Arthroplasty Revision: A Retrospective and Mini-Review Study.

OBJECTIVE: To investigate the application of impaction bone grafting (IBG) combined with Ti-alloy mesh for acetabular bone defect reconstruction in total hip arthroplasty (THA) revision and follow up the clinical outcomes and imaging findings. METHODS: The clinical and imaging data of patients who were admitted to our hospital from January 2000 to December 2020 and underwent acetabular bone defects reconstruction using IBG combined with titanium mesh were retrospectively analyzed. Preoperative and post-revision Oxford and Harris scores, and post-revision complications were evaluated. Radiographs were used to determine center of rotation (COR) of the hip joint, transparency line, bone graft fusion, and bone mineral density (BMD) around the hip joint. RESULTS: Significant improvement was observed in both Oxford and Harris scores (P < 0.05). The radiographs taken at the last follow-up examination showed no significant differences in the acetabulum COR, offsets, inclination angle, mean ratio of vertical value, and BMD analysis between the post-revision side and contralateral side (P > 0.05). The follow-up data showed restoration of the mesh implant and graft bone fusion. CONCLUSIONS: The application of IBG combined with titanium-alloy mesh in revision THA patients with acetabular defects was found to provide satisfactory outcomes. However, large-scale studies are still needed to further elucidate the long-term outcomes.

[Experimental study on the construction of telmisartan/collagen/polycaprolactone nerve conduit and its repair effect on rat sciatic nerve defect].

Objective: To construction the telmisartan/collagen/polycaprolactone (PCL) nerve conduit and assess its effect on repairing sciatic nerve defect in rats. Methods: The 60% collagen/hexafluoroisopropanol (HFIP) solution and 40% PCL/HFIP solution were prepared and mixed (collagen/PCL solution). Then the 0, 5, 10, and 20 mg of telmisartan were mixed with the 10 mL collagen/PCL solution, respectively. Telmisartan/collagen/PCL nerve conduits were fabricated via high voltage electrospinning technology. The structure of nerve conduit before and after crosslinking was observed by using scanning electron microscope (SEM). The drug release efficiency was detected by in vitro sustained release method. RAW264.7 cells were cultured with lipopolysaccharide to induce inflammation, and then co-cultured with nerve conduits loaded with different concentrations of telmisartan for 24 hours. The mRNA expressions of inducible nitric oxide synthase (iNOS) and Arginase 1 (Arg-1) were detected by using real-time fluorescence quantitative PCR. Forty adult Wistar rats were randomly divided into 4 groups ( n=10). After preparing 15-mm-long sciatic nerve defect, the defect was repaired by cross-linked nerve conduits loaded with 0, 5, 10, and 20 mg telmisartan in groups A, B, C, and D, respectively. After operation, the general condition of rats was observed after operation; the sciatic function index (SFI) was tested; the bridging between the nerve conduit and sciatic nerve, and the integrity of nerve conduit were observed; the tissue growth in nerve conduit and material degradation were observed by HE staining; the expressions of CD86 (M1 macrophage marker), CD206 (M2 macrophage marker), myelin basic protein (MBP), and myelin protein 0 (P0) in new tissues were also observed by immunohistochemical staining; the expressions of neurofilament 200 (NF-200) and S-100ß in new tissues were assessed by immunofluorescence staining. Results: The general observation showed that the inner diameter of the nerve conduit was 1.8 mm and the outer diameter was 2.0 mm. After cross-linking by genipin, the nanofiber became thicker and denser. The drug release test showed that the telmisartan loaded nerve conduit could be released gradually. With the increase of telmisartan content in nerve conduit, the iNOS mRNA expression decreased and the Arg-1 mRNA expression increased; and the differences between 20 mg group and other groups were significant ( P<0.05). In vivo experiment showed that all animals in each group survived until the completion of the experiment. The SFI was significantly higher in groups C and D than in groups A and B at different time points ( P<0.05) and in group D than in group C at 6 months after operation ( P<0.05). HE staining showed that there were significantly more new tissues in the middle of the nerve conduit in group D after operation than in other groups. Immunohistochemical staining showed that CD86 and CD206 stainings were positive in each group at 1 month after operation, among which group D had the lowest positive rate of CD86 and the highest positive rate of CD206, and there were significant differences in the positive rate of CD206 between group D and groups A, B, and C ( P<0.05); the MBP and P0 stainings were positive in groups C and D at 6 months, and the positive rate in group D was significantly higher than that in group C ( P<0.05). Immunofluorescence staining showed that the NF-200 and S-100ß expressions in group D were significantly higher than those in other groups. Conclusion: Telmisartan/collagen/PLC nerve conduit can promote the sciatic nerve defect repair in rats through promoting the polarization of M1 macrophages to M2 macrophages, and the nerve conduit loaded with20 mg telmisartan has the most significant effect.

Enhanced in vitro cytotoxicity and antitumor activity in vivo of iridium(III) complexes liposomes targeting endoplasmic reticulum and mitochondria.

In this paper, two new iridium(III) complexes [Ir(ppy)2(CBIP)](PF6) (ppy = 2-phenylpyridine, CBIP = 2-(4'-chloro-(1,1'-biphenyl))-1H-imidazo[4,5-f][1,10]phenanthroline) (Ir1) and [Ir(piq)2(CBIP)](PF6) (piq = 1-phenylisoquinoline) (Ir2) were synthesized and characterized. The anticancer activity of the complexes against cancer A549, HepG2, SGC-7901, BEL-7402, HeLa and LO2 cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Unexpectedly, the complexes exhibit no or low cytotoxic activity toward the selected cancer cells. To increase the anticancer activity, complexes Ir1 and Ir2 were encapsulated into the liposome to form Ir1lipo and Ir2lipo, while Ir1lipo and Ir2lipo show high cytotoxic efficacy against BEL-7402, SGC-7901 and HeLa cells and Ir2lipo displays moderate cytotoxic activity against A549 and HepG2. The anticancer mechanism was explored through wound healing, cell cycle arrest, apoptosis, the change of mitochondrial membrane potential and antitumor activity in vivo. The antitumor in vivo showed that Ir1Lipo (3.9 mg/kg) exhibited significant antitumor activity with an inhibitory rate of 62.16%. Additionally, the expression of B-cell lymphoma-2 family proteins was studies by western blotting analysis. The results demonstrate that Ir1lipo and Ir2lipo induce apoptosis in BEL-7402 cells via endoplasmic reticulum stress-mitochondrial pathway.

Elimination of Hole Mouth Burr in Multilayer PCB Micro-Hole by Using Micro-EDM.

The micro-hole is a key structure in multilayer printed circuit board (PCB), as it enables the effective transmission of electrical signals. At present, the most common way to machine PCB micro-holes is mechanical drilling using micro-bit. However, in the mechanical drilling of micro-holes, these holes are prone to burring at the hole mouth due to the micro-bit failing to cleanly cut through the first layer of copper foil on the PCB. Hole mouth burr can seriously affect the performance of the PCB, resulting in potential short circuiting or even ruining the PCB. To solve the above problems, this paper proposed to machine the first layer of copper foil on the PCB via micro electro-discharge machining (micro-EDM) to eliminate hole mouth burr. Compared with the mechanical drilling, micro-EDM is a form of non-contact machining, and the high temperature generated from the electric spark discharge can erode the first layer of copper foil, thus fully eliminating hole mouth burr. This paper performed a detailed study of the influence of spindle speed, machining voltage, pulse width, and pulse interval on hole mouth quality. After that, the technological parameters for eliminating hole mouth burr were obtained. Finally, under the effects of 20,000 rpm spindle speed, 26 V machining voltage, 4 µs pulse width, and 8 µs pulse interval, a micro-bit with a diameter of 200 µm was used to perform micro-EDM of the first layer of copper foil. From the machining results, it can be known that the PCB micro-hole was possessed of overall good quality, with good hole wall surface quality and almost no visible hole mouth burr.

Experimental Study on Machinability of Zr-Based Bulk Metallic Glass during Micro Milling.

The micro machinability of Zr41.2Ti13.8Cu12.5Ni10Be22.5 bulk metallic glass (BMG) was investigated by micro milling with coated cemented carbide tools. The corresponding micro milling tests on Al6061 were conducted for comparison. The results showed that the tool was still in stable wear stage after milling 300 mm, and the surface roughness Ra could be maintained around 0.06 µm. The tool experienced only slight chipping and rubbing wear after milling the BMG, while a built-up edge and the coating peeling off occurred severely when milling Al6061. The influence of rotation speed on surface roughness was insignificant, while surface roughness decreased with the reduction of feed rate, and then increased dramatically when the feed rate was below 2 µm/tooth. The surface roughness increased gradually with the axial depth of cut (DOC). Milling force decreased slightly with the increase in rotation speed, while it increased with the increase in axial DOC, and the size effect on milling force occurred when the feed rate decreased below 1 µm/tooth. The results of X-ray diffraction (XRD) showed that all milled surfaces were still dominated by an amorphous structure. This study could pave a solid foundation for structural and functional applications.

Processing Characteristics of Micro Electrical Discharge Machining for Surface Modification of TiNi Shape Memory Alloys Using a TiC Powder Dielectric.

Titanium-nickel shape memory alloy (SMA) has good biomedical application value as an implant. Alloy corrosion will promote the release of toxic nickel ions and cause allergies and poisoning of cells and tissues. With this background, surface modification of TiNi SMAs using TiC-powder-assisted micro-electrical discharge machining (EDM) was proposed. This aims to explore the effect of the electrical discharge machining (EDM) parameters and TiC powder concentration on the machining properties and surface characteristics of the TiNi SMA. It was found that the material removal rate (MRR), surface roughness, and thickness of the recast layer increased with an increase in the discharge energy. TiC powder's addition had a positive effect on increasing the electro-discharge frequency and MRR, reducing the surface roughness, and the maximum MRR and the minimum surface roughness occurred at a mixed powder concentration of 5 g/L. Moreover, the recast layer had good adhesion and high hardness due to metallurgical bonding. XRD analysis found that the machined surface contains CuO2, TiO2, and TiC phases, contributing to an increase in the surface microhardness from 258.5 to 438.7 HV, which could be beneficial for wear resistance in biomedical orthodontic applications.

[Effects of basic periodontal treatment on endothelin, vascular endothelial growth factor-A and tumor necrosis factor-α levels in gingival crevicular fluid and serum].

PURPOSE: To investigate the effects of basic periodontal treatment on the levels of endothelin (ET), vascular endothelial growth factor-A (VEGF-A) and tumor necrosis factor-α (TNF-α) in gingival crevicular fluid and serum. METHODS: A total of 57 patients with periodontitis (experimental group) and 43 healthy examinees (control group) admitted to Shenzhen Hospital of Guangzhou University of Chinese Medicine from October to May 2018 were selected. Patients received subgingival scaling and root planing for 6 weeks. Then various indexes were compared, including bleeding on probing (BOP), plaque index (PI), probe depth (PD), clinical attachment level (CAL) and gingival index (GI), as well as the levels of ET, VEGF-A and TNF-α in gingival crevicular fluid and serum. The correlation between ET, VEGF-A and TNF-α was analyzed. The data were analyzed with SPSS 21.0 software package. RESULTS: Periodontal indexes including BOP, PI, PD, CAL and GI in the experimental group were significantly increased after treatment (P<0.05), but still significantly lower than those in the control group (P<0.05). The levels of ET, VEGF-A and TNF-α in gingival crevicular fluid and serum were significantly decreased in the experimental group after treatment (P<0.05), but significantly higher than those in the control group (P<0.05). The level of ET in gingival crevicular fluid was not significantly correlated with VEGF-A level in patients with periodontitis (P>0.05), while was positively correlated with VEGF-A levels (P<0.05). CONCLUSIONS: Basic periodontal treatment can reduce the levels of ET, VEGF-A and TNF-α in gingival crevicular fluid and serum of patients with periodontitis, and improve the periodontal status; moreover, ET level in gingival crevicular fluid is positively correlated with TNF-α level.

Hydrogen-assisted Carbon Dioxide Thermochemical Reduction on La0.9 Ca0.1 FeO3-δ Membranes: A Kinetics Study.

Kinetics data for CO2 thermochemical reduction in an isothermal membrane reactor is required to identify the rate-limiting steps. A detailed reaction kinetics study on this process supported by an La0.9 Ca0.1 FeO3-δ (LCF-91) membrane is thus reported. The dependence of CO2 reduction rate on various operating conditions is examined, such as CO2 concentration on the feed side, fuel concentrations on the sweep side, and temperatures. The CO2 reduction rate is proportional to the oxygen flux across the membrane, and the measured maximum fluxes are 0.191 and 0.164 µmol cm-2 s-1 with 9.5 mol% H2 and 11.6 mol% CO on the sweep side at 990 °C, respectively. Fuel is used to maintain the chemical potential gradient across the membrane and CO is used to derive the surface reaction kinetics. This membrane also exhibits stable performances for 106 h. A resistance-network model is developed to describe the oxygen transport process and the kinetics data are parameterized using the experimental values. The model shows a transition of the rate limiting step between the surface reactions on the feed side and the sweep side depending on the operating conditions.

Pyroptosis induced by enterovirus 71 and coxsackievirus B3 infection affects viral replication and host response.

Enterovirus 71 (EV71) is the primary causative pathogen of hand, foot, and mouth disease (HFMD), affecting children with severe neurological complications. Pyroptosis is a programmed cell death characterized by cell lysis and inflammatory response. Although proinflammatory response has been implicated to play important roles in EV71-caused diseases, the involvement of pyroptosis in the pathogenesis of EV71 is poorly defined. We show that EV71 infection induced caspase-1 activation. Responding to the activation of caspase-1, the expression and secretion of both IL-1ß and IL-18 were increased in EV71-infected cells. The treatment of caspase-1 inhibitor markedly improved the systemic response of the EV71-infected mice. Importantly, caspase-1 inhibitor suppressed EV71 replication in mouse brains. Similarly, pyroptosis was activated by the infection of coxsackievirus B3 (CVB3), an important member of the Enterovirus genus. Caspase-1 activation and the increased expression of IL-18 and NLRP3 were demonstrated in HeLa cells infected with CVB3. Caspase-1 inhibitor also alleviated the overall conditions of virus-infected mice with markedly decreased replication of CVB3 and reduced expression of caspase-1. These results indicate that pyroptosis is involved in the pathogenesis of both EV71 and CVB3 infections, and the treatment of caspase-1 inhibitor is beneficial to the host response during enterovirus infection.

Preclinical Evaluation of Liposomal C8 Ceramide as a Potent anti-Hepatocellular Carcinoma Agent.

Hepatocellular carcinoma (HCC) remains a global health threat. The search for novel anti-HCC agents is urgent. In the current study, we synthesized a liposomal C8 ceramide, and analyzed its anti-tumor activity in pre-clinical HCC models. The liposomal C8 (ceramide) potently inhibited HCC cell (HepG2, SMMC-7721 and Huh-7 lines) survival and proliferation, more efficiently than free C8 ceramide. Yet, non-cancerous HL7702 human hepatocytes were resistant to the liposomal C8 treatment. Liposomal C8 activated caspase-dependent apoptosis in HCC cells, and HCC cytotoxicity by liposomal C8 was significantly attenuated with co-treatment of caspase inhibitors. At the molecular level, we showed that liposomal C8 activated ASK1 (apoptosis signal-regulating kinase 1)-JNK (Jun N-terminal protein kinase) signaling in HCC cells. On the other hand, JNK pharmacological inhibition or dominant negative mutation, as well as ASK1 shRNA-knockdown remarkably inhibited liposomal C8-induced apoptosis in HCC cells. Further studies showed that liposomal C8 inhibited AKT-mTOR (mammalian target of rapamycin) activation in HCC cells. Restoring AKT-mTOR activation by introducing a constitutively-active AKT alleviated HepG2 cytotoxicity by liposomal C8. In vivo, intravenous (i.v.) injection of liposomal C8 significantly inhibited HepG2 xenograft growth in severe combined immuno-deficient (SCID) mice, and mice survival was significantly improved. These preclinical results suggest that liposomal C8 could be further studied as a valuable anti-HCC agent.