Polysaccharide-Based Coating with Excellent Antibiofilm and Repeatable Antifouling-Bactericidal Properties for Treating Infected Hernia.

In recent years, the utilization of medical devices has gradually increased and implantation procedures have become common treatments. However, patients are susceptible to the risk of implant infections. This study utilized chemical grafting to immobilize polyethylenimine (QPEI) and hyaluronic acid (HA) on the surface of the mesh to improve biocompatibility while being able to achieve antifouling antimicrobial effects. From the in vitro testing, PP-PDA-Q-HA exhibited a high antibacterial ratio of 93% against S. aureus, 93% against E. coli, and 85% against C. albicans. In addition, after five rounds of antimicrobial testing, the coating continued to exhibit excellent antimicrobial properties; PP-PDA-Q-HA also inhibits the formation of bacterial biofilms. In addition, PP-PDA-Q-HA has good hemocompatibility and cytocompatibility. In vivo studies in animal implantation infection models also demonstrated the excellent antimicrobial properties of PP-PDA-Q-HA. Our study provides a promising strategy for the development of antimicrobial surface medical materials with excellent biocompatibility.

Design, synthesis, and hypoxia-inducible factor-1α inhibitory activity evaluation of panaxadiol derivatives containing a thiazole moiety.

The hypoxia-inducible factor-1α (HIF-1α) pathway has been implicated in tumor angiogenesis, growth, and metastasis. Therefore, the inhibition of this pathway is an important therapeutic target for cancer. Here, three series of panaxadiol derivatives containing a thiazole moiety (5a-l, 7a-i, and 9a-i) were synthesized and evaluated for HIF-1α inhibitory activity using a Hep3B cell-based luciferase reporter assay. Compounds 5d and 7b showed the strongest inhibitory activity with IC50 values of 17.37 and 6.42 µM, respectively, and did not show any significant cytotoxicity. Western blot assay results indicated that these two compounds exhibited more potent inhibition, compared with panaxadiol, of the expression of HIF-1α protein in Hep3B cells at a concentration of 50 µM. Molecular docking experiments were also performed to investigate the structure-activity relationship.

Insight into microvascular adaptive alterations in the Glisson system of biliary atresia after Kasai portoenterostomy using X-ray phase-contrast CT.

OBJECTIVES: To investigate microvascular alterations in the Glisson system of biliary atresia (BA) patients after Kasai portoenterostomy (KP) using three-dimensional (3D) virtual histopathology based on X-ray phase-contrast CT (PCCT). METHODS: Liver explants from BA patients were imaged using PCCT, and 32 subjects were included and divided into two groups: KP (n = 16) and non-KP (n = 16). Combined with histological analysis and 3D visualization technology, 3D virtual histopathological assessment of the biliary, arterial, and portal venous systems was performed. According to loop volume ratio, 3D spatial density, relative surface area, tortuosity, and other parameters, pathological changes of microvasculature in the Glisson system were investigated. RESULTS: In the non-KP group, bile ducts mostly manifested as radial multifurcated hyperplasia and twisted into loops. In the KP group, the bile duct hyperplasia was less, and the loop volume ratio of bile ducts decreased by 13.89%. Simultaneously, the arterial and portal venous systems presented adaptive alterations in response to degrees of bile duct hyperplasia. Compared with the non-KP group, the 3D spatial density of arteries in the KP group decreased by 3.53%, and the relative surface area decreased from 0.088 ± 0.035 to 0.039 ± 0.015 (p < .01). Deformed portal branches gradually recovered after KP, with a 2.93% increase in 3D spatial density and a decrease in tortuosity from 1.17 ± 0.06 to 1.14 ± 0.04 (p < .01) compared to the non-KP group. CONCLUSION: 3D virtual histopathology via PCCT clearly reveals the microvascular structures in the Glisson system of BA patients and provides key insights into the morphological mechanism of microvascular adaptation induced by biliary tract dredging after KP in BA disease. KEY POINTS: • 3D virtual histopathology via X-ray phase-contrast computed tomography clearly presented the morphological structures and pathological changes of microvasculature in the Glisson system of biliary atresia patients. • The morphological alterations of microvasculature in the Glisson system followed the competitive occupancy mechanism in the process of biliary atresia.

Chemical vapor deposition of uniform bilayer PtS2 flakes for electrocatalytic hydrogen evolution.

Two-dimensional (2D) 1T-PtS2 has been drawing considerable attention due to its highly layer-dependent bandgap, high carrier mobility, superior air stability, etc. However, the growth of 2D PtS2 with uniform thickness and controllable shape remains an immense challenge. Herein, the uniform bilayer (2L) 1T-PtS2 single crystals are controllably grown on mica using chemical vapor deposition for the first time. The variable morphology from triangular to hexagonal can be obtained by regulating growth temperature. Significantly, the 2L PtS2 flakes show a good electrocatalytic hydrogen evolution reaction (HER) property with an overpotential of 184 mV at 10 mA cm-2, Tafel slope of 81 mV dec-1, exchange current density of 43 µA cm-2, and outstanding stability. This work manifests that 2D PtS2 is a promising candidate for HER applications.

First-principles study on photoelectric properties of all-inorganic two-dimensional double perovskite Cs3AgBiBr7.

Two-dimensional (2D) all-inorganic double perovskite materials have attracted great interest owing to their unique photoelectric characteristics, such as high quantum efficiency and relative stability. However, few studies have been conducted on the 2D all-inorganic double perovskite Cs3AgBiBr7, and its photoelectric properties are unclear. In this study, we present a detailed investigation of the band structure, optical absorption spectrum, carrier mobility and exciton binding energy of the double perovskite Cs3AgBiBr7 based on the first-principles. The results show that this system has an indirect band gap and low carrier mobility, high exciton binding energy (2041.38 meV) and significant light absorption in the UV region. We also find that the material may be a potential exciton insulation candidate owing to the exciton binding energy beyond the band gap. Our calculated results also show that low dimensional perovskite Cs3AgBiBr7 is more suitable for luminescence than a photovoltaic device. We hope our theoretical results will inspire and promote the experimental exploration of 2D all-inorganic double perovskite materials for photoelectric applications.

Interfacial contact barrier and charge carrier transport of MoS2/metal(001) heterostructures.

The rapid rise of two-dimensional (2D) materials has aroused increasing interest in the fields of microelectronics and optoelectronics; various types of 2D van der Waals heterostructures (vdWHs), especially those based on MoS2, have been widely investigated in theory and experiment. However, the interfacial properties of MoS2 and the uncommon crystal surface of traditional three-dimensional (3D) metals are yet to be explored. In this paper, we studied heterostructures composed of MoS2 and metal(001) slabs, based on the first-principles calculations, and we uncovered that MoS2/Au(001) and MoS2/Ag(001) vdWHs reveal Schottky contacts, and MoS2/Cu(001) belongs to Ohmic contact and possesses ultrahigh electron tunneling probability at the equilibrium distance. Thus, the MoS2/Cu(001) heterostructure exhibits the best contact performance. Further investigations demonstrate that external longitudinal strain can modulate interfacial contact to engineer the Schottky-Ohmic contact transition and regulate interfacial charge transport. We believe that it is a general strategy to exploit longitudinal strain to improve interfacial contact performance to design and fabricate a multifunctional MoS2-based electronic device.

Two new iridoid glycosides from Odontites vulgaris.

Two new iridoid glycosides, named 3'-O-benzoyl-dolichocymboside D (1) and dolichocymboside E (2), along with ten known glycosides (3-12), were isolated from the ethanol extract of the whole plants of Odontites vulgaris Moench. The structures of the isolated compounds were elucidated by 1D and 2D NMR and HR-ESI-MS spectra and by comparison with those reported in the literature. This is the first report on compounds 11 and 12 isolated from the family Scrophulariaceae, and compounds 8-10 were isolated from the genus Odontites.

Application of Quinoline Ring in Structural Modification of Natural Products.

Natural compounds are rich in pharmacological properties that are a hot topic in pharmaceutical research. The quinoline ring plays important roles in many biological processes in heterocycles. Many pharmacological compounds, including saquinavir and chloroquine, have been marketed as quinoline molecules with good anti-viral and anti-parasitic properties. Therefore, in this review, we summarize the medicinal chemistry of quinoline-modified natural product quinoline derivatives that were developed by several research teams in the past 10 years and find that these compounds have inhibitory effects on bacteria, viruses, parasites, inflammation, cancer, Alzheimer's disease, and others.

Nine New Pregnane Glycosides from the Cultivated Medicinal Plant Marsdenia tenacissima.

The ethnobotanical plant Marsdenia tenacissima has been used for hundreds of years for Dai people in Yunnan Province, China. Previously, chemical investigations on this plant have revealed that pregnane glycosides were the main biological constituents. Nine new pregnane glycosides, marsdeosides A-I (1-9), were isolated from cultivated dried stems of the medicinal plant Marsdenia tenacissima in this study. The structures were analyzed by extensive spectroscopic analysis, including 1D, 2D NMR, HRESIMS, and IR spectroscopic analysis. The absolute configurations of the sugar moieties were identified by comparing the Rf values and specific optical rotations with those of the commercially available standard samples and the data reported in the literature. Marsdeosides A (1) featured an unusual 8,14-seco-pregnane skeleton. Compounds 1, 8, and 9 showed activity against nitric oxide production in lipopolysaccharide-activated macrophage RAW264.7, with IC50 values of 37.5, 38.8, and 42.8 µM (L-NMMA was used as a positive control, IC50 39.3 µM), respectively. This study puts the knowledge of the chemical profile of the botanical plant M. tenacissima one step forward and, thereby, promotes the sustainable utilization of the resources of traditional folk medicinal plants.

The L-shaped tunnel technique showed favourable outcomes similar to those of the Y-graft technique in anatomic lateral ankle ligament reconstruction.

PURPOSE: To compare the mid- to long-term clinical and radiological outcomes of the confluent L-shaped tunnel technique with the Y-graft technique for anatomic lateral ankle ligament reconstruction. METHODS: This retrospective study involved 41 patients who underwent lateral ankle ligament reconstruction between 2013 and 2018. Based on the tunnel direction and tendon fixation method at the fibula side, patients were divided into two groups, with 17 patients in the L-shaped tunnel group and 24 patients in the Y-graft group. The American Orthopaedic Foot and Ankle Society (AOFAS) score, visual analogue scale (VAS) pain score, Tegner score, and Karlsson score were evaluated and compared preoperatively and at follow-up. Anterior talar translation and talar tilt at stress radiographs, postoperative sprain recurrence, range of motion (ROM) restriction, sensory disturbance, etc., were also collected and compared. RESULTS: The mean follow-up times were 72 and 42 months for the L-shaped group and Y-graft group, respectively. The median VAS pain score, Tegner score, AOFAS score, Karlsson score significantly improved from a preoperative level in both groups (all with p < 0.01). No significant difference was found between the two groups regarding the changes from preoperatively to postoperatively except for the VAS pain score reduction (1.58 ± 1.58 in the L-shaped group vs. 2.53 ± 1.29 in the Y-graft group, p = 0.035). The incidence of flexion-extension ROM restriction (≥ 5°) was significantly higher in the Y-graft group (41.2%) than in the L-shaped group (12.5%) (p = 0.035). CONCLUSIONS: Both the confluent L-shaped tunnel technique and the Y-graft technique significantly improved symptoms, ankle function, and radiographic outcomes in patients with chronic lateral ankle instability (CLAI) at mid- to long-term follow-up. The confluent L-shaped tunnel technique resulted in lower rates of flexion-extension ROM restriction, while the Y-graft technique showed better VAS pain reduction. This result could provide further evidence for the surgical treatment of CLAI. LEVEL OF EVIDENCE: III.

The anti-tussive, anti-inflammatory effects and sub-chronic toxicological evaluation of perilla seed oil.

BACKGROUND: Perilla seed oil (PSO) is the main constituent of perilla seeds currently being used in the food industry, however it also has great clinical potential in the regulation of lung function as a nutrition supplement because of the high content of α-linolenic acid (ALA). In this study, the pharmacological activities including anti-tussive, expectorant and anti-inflammatory effect of PSO were performed. Furthermore, the 90-day sub-chronic oral toxicity with a 30 day recovery period was evaluated in Wistar rats. RESULTS: The pharmacological studies demonstrated that PSO inhibited cough frequency induced by capsaicine in mice. PSO also inhibited the leukotriene B4 (LTB4) release from the calcium ionophore A23187-induced polymorphonuclear neutrophils (PMNs) to some extent. In this sub-chronic toxicity study, mortality, clinical signs, body weight, food consumption, hematology, serum biochemistry, urinalysis, organ weight, necropsy, and histopathology were used to evaluate the toxicity of PSO. Lower body weight and various negative impacts on liver related parameters without histopathological lesion were observed in the 16 g kg-1 groups. No clinically significant changes were discovered in the 4 g kg-1 group during the test period. CONCLUSION: In summary, PSO exhibited anti-tussive and anti-inflammatory activities in vivo and in vitro. These sub-chronic toxicity studies inferred that the 'no-observed adverse effect level' (NOAEL) of PSO in Wistar rats was determined to be 4 g kg-1 . These results may provide a safety profile and a valuable reference for the use of PSO. © 2020 Society of Chemical Industry.

Synthesis and evaluation of HIF-1α inhibitory activities of novel panaxadiol derivatives.

Hypoxia-inducible factor 1α (HIF-1α) is a known regulator of tumor cell proliferation, migration, and angiogenesis. The presence of a high concentration of HIF-1α is positively correlated with the severity of cancer. Therefore, the inhibition of this pathway represents an important therapeutic target for the treatment of various types of cancer. Here, we designed and synthesized 30 panaxadiol (PD) derivatives and evaluated their inhibitory activities against HIF-1α transcription. Of these, compound 3l exhibited the most promising inhibitory activity (IC50 = 3.7 µM) and showed significantly decreased cytotoxicity compared with PD. Compound 9e exhibited the strongest cytotoxic effect and may be considered for further preclinical development.

Antimicrobial Peptide-Conjugated Hierarchical Antifouling Polymer Brushes for Functionalized Catheter Surfaces.

Catheter-related infection is a great challenge to modern medicine, which causes significant economic burden and increases patient morbidity. Hence, there is a great requirement for functionalized surfaces with inherently antibacterial properties and biocompatibility that prevent bacterial colonization and attachment of blood cells. Herein, we developed a strategy for constructing polymer brushes with hierarchical architecture on polyurethane (PU) via surface-initiated atom-transfer radical polymerization (SI-ATRP). Surface-functionalized PU (PU-DMH) was readily prepared, which comprised of poly(3-[dimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]azaniumyl]propane-1-sulfonate) (PDMAPS) brushes as the lower layer and antimicrobial peptide-conjugated poly(methacrylic acid) (PMAA) brushes as the upper layer. The PU-DMH surface showed excellent bactericidal property against both Gram-positive and Gram-negative bacteria and could prevent accumulation of bacterial debris on surfaces. Simultaneously, the PU-DMH samples possessed good hemocompatibility and low cytotoxicity. Furthermore, the integrated antifouling and bactericidal properties of PU-DMH under hydrodynamic conditions were confirmed by an in vitro circulating model. The functionalized surface possessed persistent antifouling and bactericidal performances both under static and hydrodynamic conditions. The microbiological and histological results of animal experiments also verified the in vivo anti-infection performance. The present work might find promising clinical applications for preventing catheter-related infection.

Semi-synthesis and anti-tumor activity of novel 25-OCH3-PPD derivatives incorporating aromatic moiety.

Previously we have reported that 25-OCH3-PPD could suppress the reproduction of cancer cells and cause apoptosis without obvious toxicity. Herein, we aimed to enhance its bioactivity by introducing aromatic groups to its dammarane-type skeleton. These synthesized derivatives were tested for their inhibitory activities against five cancer cell lines. Of them, compounds 3a, 14a and 18a had the strongest antiproliferative activities against tumor cells (IC50 < 15 µM, 5-fold to 10-fold increases than 25-OCH3-PPD). Especially compound 14a displayed the most potent activity against DU145, MCF-7 and HepG2 cells (IC50 = 6.7 ±â€¯0.8, 4.3 ±â€¯0.8 and 5.8 ±â€¯0.6 µM, respectively). Structure-activity relationships demonstrated that having aromatic ester at the C3 position could improve the bioactivity. The data provided new insights into exploring novel antiproliferative lead compounds.

Acute and sub-chronic 90-day oral toxicity study of Perilla seed oil in rodents and Beagle dogs.

Perilla seeds are used as food and traditional medicine in China. This study aimed to investigate the toxicity profile of Perilla seed oil (PSO), which is the main constituent of Perilla seeds in rodents and Beagle dogs. No significant treatment-associated toxicity or mortality was observed at PSO dosages of up to 50 g/kg and 20 g/kg in KM mice and Wistar rats, respectively, suggesting that PSO was well tolerated by the experimental rodents. Sub-chronic oral toxicity of PSO was studied in dogs at doses of 3, 6 and 12 g/kg/d for 90 days followed by a 30 day recovery period. The results indicated that the body weight increased in all-dose groups more than control group, typical of animals on diets rich in fatty acids. Treatment-related side effects, including changes in hematology and serum biochemistry parameters, histopathology of liver and lymph glands, were observed in the high and moderate-dose dogs. However, these changes disappeared after the doses were withdrawn during the recovery period, except for alteration of liver in the high-dose group. In conclusion, the "no observed adverse effect level" (NOAEL) of oral administration of PSO for 90 days in Beagle dogs was considered to be 3 g/kg/d.

High transport and excellent optical property of a two-dimensional single-layered hybrid perovskite (C4H9NH3)2PbBr4: a theoretical study.

Organic-inorganic hybrid perovskites are developed to pursue high charge carrier mobility and light absorption coefficient. In this study, we present a detailed comparative research of the atomic and electronic structures of single-layered perovskites (C4H9NH3)2PbBr4 with two-dimensional/three-dimensional (2D/3D) spatial arrangement to predict the in plane charge carrier mobility along with the charge effective mass, elastic constant, and deformation potential. The calculated results reveal that the intrinsic in plane carrier mobilities of 2D single-layered hybrid perovskite (C4H9NH3)2PbBr4 along the 100 and 010 directions are superior to those of the 3D structure. Furthermore, the optical properties are calculated from the electronic structure; it is found that the light absorption spectrum of 2D single-layered perovskite (C4H9NH3)2PbBr4 with a high absorption coefficient is wider than that of the 3D phase. We speculate that the superior mobility and wider absorption spectrum of the 2D mono-layered perovskite are due to high charge density and ferroelectricity originating from structure distortion upon 3D-to-2D structure transformation. These results indicate that the 2D single-layered hybrid perovskite (C4H9NH3)2PbBr4 is a potential candidate for application in the optoelectronic and photovoltaic fields.

Pressure-induced strong ferroelectric polarization in tetra-phase perovskite CsPbBr3.

Ab initio simulations combined with the Berry phase method are employed to investigate ferroelectric polarization of tetragonal CsPbBr3 crystals by applying hydrostatic pressure varying from 0 to 19 GPa; we find that the object research belongs to the P4mm space group. The calculated results show that the materials undergo a paraelectric-ferroelectric phase transition when the pressure increases to a critical value 15 GPa. The polarization is strongly enhanced and attains a high value of about 23 µC cm-2, owing to the increase in the ionic and electric contributions to the polarization under compressive strain. We present a detailed theoretical investigation to analyze the origin of polarization. The ionic polarization is mainly ascribed to the central displacements of Pb2+ cations and Br- anions induced by a highly distorted octahedral PbBr6- framework. Electronic structure calculations suggest that asymmetric hopping p orbital electrons of Br(3) ions are responsible for the enhancement in electric polarization. These discoveries suggest that tetragonal CsPbBr3 has significant potential in future ferroelectric applications, and this can broaden the application field from optoelectronics to ferroelectrics.

20(S)-25-methoxyl-dammarane-3ß, 12ß, 20-triol negatively regulates activation of STAT3 and ERK pathways and exhibits anti-cancer effects in HepG2 cells.

The pro-inflammatory cytokine interleukin 6 (IL-6), via activating its downstream JAK/STAT3 and Ras/ERK signaling pathways, is involved in cell growth, proliferation and anti-apoptotic activities in various malignancies. To screen inhibitors of IL-6 signaling, we constructed a STAT3 and ERK dual-pathway responsive luciferase reporter vector (Co.RE). Among several candidates, the natural compound 20(S)-25-methoxyl-dammarane-3ß, 12ß, 20-triol (25-OCH3-PPD, GS25) was identified to clearly inhibit the luciferase activity of Co.RE. GS25 was confirmed to indeed inhibit activation of both STAT3 and ERK pathways and expression of downstream target genes of IL-6, and to predominantly decrease the viability of HepG2 cells via induction of cell cycle arrest and apoptosis. Interestingly, GS25 showed preferential inhibition of HepG2 cell viability relative to normal liver L02 cells. Further investigation showed that GS25 could not induce apoptosis and block activation of STAT3 and ERK pathways in L02 cells as efficiently as in HepG2 cells, which may result in differential effects of GS25 on malignant and normal liver cells. In addition, GS25 was found to potently suppress the expression of endogenous STAT3 at a higher concentration and dramatically induce p38 phosphorylation in HepG2 cells, which could mediate its anti-cancer effects. Finally, we demonstrated that GS25 also inhibited tumor growth in HepG2 xenograft mice. Taken together, these findings indicate that GS25 elicits its anti-cancer effects on HepG2 cells through multiple mechanisms and has the potential to be used as an inhibitor of IL-6 signaling. Thus, GS25 may be developed as a treatment for hepatocarcinoma with low toxicity on normal liver tissues as well as other inflammation-associated diseases.

Sulfamic and succinic acid derivatives of 25-OH-PPD and their activities to MCF-7, A-549, HCT-116, and BGC-823 cell lines.

In the search for new anti-tumor agents with higher potency than our previously identified compound 1 (25-OH-PPD, 25-hydroxyprotopanaxadiol), 12 novel sulfamic and succinic acid derivatives that could improve water solubility and contribute to good drug potency and pharmacokinetic profiles were designed and synthesized. Their in vitro anti-tumor activities in MCF-7, A-549, HCT-116, and BGC-823 cell lines and one normal cell line were tested by standard MTT assay. Results showed that compared with compound 1, compounds 2, 3, and 7 exhibited higher cytotoxic activity on A-549 and BGC-823 cell lines, together with lower toxicity in the normal cell. In particular, compound 2 exhibited the best anti-tumor activity in the in vitro assays, which may provide valuable data for the research and development of new anti-tumor agents.

In vitro assessment of the glucose-lowering effects of berberrubine-9-O-ß-D-glucuronide, an active metabolite of berberrubine.

Berberrubine (BRB) is the primary metabolite of berberine (BBR) that has shown a stronger glucose-lowering effect than BBR in vivo. On the other hand, BRB is quickly and extensively metabolized into berberrubine-9-O-ß-D-glucuronide (BRBG) in rats after oral administration. In this study we compared the pharmacokinetic properties of BRB and BRBG in rats, and explored the mechanisms underlying their glucose-lowering activities. C57BL/6 mice with HFD-induced hyperglycemia were administered BRB (50 mg·kg-1·d-1, ig) for 6 weeks, which caused greater reduction in the plasma glucose levels than those caused by BBR (120 mg·kg-1·d-1) or BRB (25 mg·kg-1·d-1). In addition, BRB dose-dependently decreased the activity of α-glucosidase in gut of the mice. After oral administration of BRB in rats, the exposures of BRBG in plasma at 3 different dosages (10, 40, 80 mg/kg) and in urine at different time intervals (0-4, 4-10, 10-24 h) were dramatically greater than those of BRB. In order to determine the effectiveness of BRBG in reducing glucose levels, we prepared BRBG from the urine pool of rats, and identified and confirmed it through LC-MS-IT-TOF and NMR spectra. In human normal liver cell line L-O2 in vitro, treatment with BRB or BRBG (5, 20, 50 µmol/L) increased glucose consumption, enhanced glycogenesis, stimulated the uptake of the glucose analog 2-NBDG, and modulated the mRNA levels of glucose-6-phosphatase and hexokinase. However, both BBR and BRB improved 2-NBDG uptake in insulin-resistant L-O2 cells, while BRBG has no effect. In conclusion, BRB exerts a stronger glucose-lowering effect than BBR in HFD-induced hyperglycemia mice. Although BRB significantly stimulated the insulin sensitivity and glycolysis in vitro, BRBG may have a greater contribution to the glucose-lowering effect because it has much greater system exposure than BRB after oral administration of BRB. The results suggest that BRBG is a potential agent for reducing glucose levels.