PMA induces vaccine adjuvant activity by the modulation of TLR signaling pathway.

Toll-like receptor (TLR) ligands are being developed for use as vaccine adjuvants and as immunomodulators because of their ability to stimulate innate and adaptive immune responses. Flagellin, a TLR5 ligand, was reported to show potent mucosal vaccine adjuvant activity. To identify ligands that potentiate the adjuvant activity of flagellin, we screened a plant library using HEK293T cells transiently cotransfected with phTLR5 and pNF- κ B-SEAP plasmids. The 90% EtOH extract from Croton tiglium showed significant NF- κ B transactivation in a TLR5-independent manner along with the increase of a flagellin activity. We have studied to characterize an active component from Croton tiglium and to elucidate the action mechanisms. Phorbol 12-myristate 13-acetate (PMA) was isolated as an active component of Croton tiglium by activity-guided fractionation, column chromatography, HPLC, NMR, and MS. PMA at a range of nM induced PKC-dependent NF- κ B activation and IL-8 production in both TLR5- and TLR5+ assay systems. In in vivo mouse vaccination model, PMA induced antigen-specific IgG and IgA antibody responses and increased IL-12 production corresponding to T cell responses in spleen lymphocytes. These results suggest that PMA would serve as an efficacious mucosal vaccine adjuvant.

LAMP1 controls CXCL10-CXCR3 axis mediated inflammatory regulation of macrophage polarization during inflammatory stimulation.

Increased expression of CXCL10 and its receptor CXCR3 represents an inflammatory response in cells and tissues. Macrophage polarization and autophagy are major functions in inflammatory macrophages; however, the cellular functions of the CXCL10-CXCR3 axis in macrophages are not well understood. Here, we examined the role of CXCL10-CXCR3-axis-regulated autophagy in macrophage polarization. First, in non-inflammatory macrophages, whereas CXCL10 promotes M2 polarization and inhibits M1 polarization, CXCR3 antagonist AMG487 induces the opposite macrophage polarization. Next, CXCL10 promotes the expression of autophagy proteins (Atg5-Atg12 complex, p62, LC3-II, and LAMP1) and AMG487 inhibits their expression. Knockdown of LAMP1 by short interfering RNA switches the CXCL10-induced polarization from M2 to M1 in non-inflammatory macrophages. Furthermore, in inflammatory macrophages stimulated by poly(I:C), CXCL10 induces M1 polarization and AMG487 induces M2 polarization in association with a decrease in LAMP1. Finally, AMG487 alleviates lung injury after poly(I:C) treatment in mice. In conclusion, CXCL10-CXCR3 axis differentially directs macrophage polarization in inflammatory and non-inflammatory states, and autophagy protein LAMP1 acts as the switch controlling the direction of macrophage polarization by CXCL10-CXCR3.

[Comparison of the efficacy of TiRobot orthopaedic robot assisted F screw technique and inverted triangle parallel nail internal fixation in the treatment of unstable femoral neck fractures].

OBJECTIVE: To compare the effectiveness of TiRobot assisted F screw technique and inverted triangle parallel nail internal fixation in the treatment of unstable femoral neck fractures. METHODS: A retrospective analysis was conducted on 72 patients with unstable femoral neck fractures who were treated with percutaneous cannulated screw fixation assisted with TiRobot Orthopaedic robot from December 2019 to April 2021. Among them, 37 patients were treated with F screw internal fixation, including 16 males and 21 females, aged 47 to 64 years old with an average of （53.87±5.28） years old；According to Pauwels classification, there were 1 case of type Ⅰ, 19 cases of type Ⅱ, 17 cases of type Ⅲ；8 cases of combined medical diseases；17 cases of falling, 8 cases of traffic accident and 12 cases of falling from height；The time from injury to operation was 29 to 49 hours with average of （35.00±7.34） hours. Another 35 cases used internal fixation with an inverted triangle parallel nail, including 13 males and 22 females with an average age of 46 to 63 years old （52.36±5.05） years old；According to the Pauwels injury classification：there were 2 cases of type Ⅰ, 21 cases of type Ⅱ, 12 cases of type Ⅲ；6 cases of medical diseases, 15 cases of falling injury, 9 cases of traffic accident, 11 cases of falling injury；The time from injury to operation was 30 to 45 hours with an average of （33.00±6.83） h. The intraoperative blood loss, operation time, intraoperative fluoroscopy times, follow-up time, fracture healing time, postoperative complications were observed and compared between the two groups. The hip joint function was evaluated by Harris score at 6 months and 12 months after operation. RESULTS: There was no significant difference in operation time, intraoperative blood loss, intraoperative fluoroscopy times and other intraoperative data between two groups（P>0.05）. Both groups were followed up regularly, and the follow-up time was 12 to 16 months. The fracture healing time and Harris score of the F screw internal fixation group were better than those of the inverted triangle parallel nail internal fixation group （P<0.05）. There was 1 case of femoral neck shortening in the F screw internal fixation group, 1 case of nonunion, 1 case of nail withdrawal, and 1 case of lower extremity deep vein thrombosis in the inverted triangle internal fixation group. The incidence of complications in the F screw internal fixation group was lower than that in the inverted triangle parallel nail internal fixation group（P<0.05）. CONCLUSION: Percutaneous cannulated F screw technique using Tirobot navigation positioning system is a safe and effective treatment for patients with unstable femoral neck fractures. It can significantly shorten the fracture healing time, reduce the incidence of postoperative complications, significantly improve hip joint function, and improve the quality of life.

Preparation of MOF/polypyrrole and flower-like MnO2 electrodes by electrodeposition: High-performance materials for hybrid capacitive deionization defluorination.

Fluorine pollution has become a global public health problem due to its adverse health effects. Adsorption is the primary method for removing fluoride from drinking water. However, the adsorption method has disadvantages such as difficulty in recovering the adsorbent, and the need to add additional chemicals for regeneration, thereby causing secondary pollution, which limits further industrial applications. Capacitive deionization (CDI), as an emerging water treatment technology, has attracted widespread attention due to its advantages of simple operation, low energy consumption and less environmental impact. In this study, a polypyrrole (PPy) film was prepared on a graphite substrate by electrodeposition, and then metal-organic framework Ce/Zn-BDC-NH2 (CZBN) was deposited on the PPy film by electrophoretic deposition to obtain CZBN/PPy electrode was obtained. The CZBN/PPy anode was then coupled with the MnO2 cathode for capacitive removal of fluoride in a CDI cell. Both CZBN/PPy and MnO2 electrodes exhibit pseudocapacitive behavior, which can selectively and reversibly intercalate F- (CZBN/PPy) and Na+ (MnO2) ions. As expected, the CZBN/PPy-MnO2 system exhibits excellent fluorine removal performance. In 1.2 V, 100 mg/L F- solution, the F- removal capacity can reach 55.12 mg/g. It has high F- selectivity in the presence of some common anions, and can maintain high F- removal ability even after five adsorption regeneration processes. The mechanism of F- removal was studied by Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS). F- was mainly removed by electrostatic interaction and ion exchange with hydroxyl. The excellent defluorination performance of the CZBN/PPy-MnO2 system makes it have good practical application prospects.

Attenuation of the extract from Moringa oleifera on monocrotaline-induced pulmonary hypertension in rats.

The purpose of this study was to determine the effects of an extract from Moringa oleifera (MO) on the development of monocrotaline (MCT)-induced pulmonary hypertension (PH) in Wistar rats. An ethanol extraction was performed on dried MO leaves, and HPLC analysis identified niaziridin and niazirin in the extract. PH was induced with a single subcutaneous injection of MCT (60 mg/kg) which resulted in increases in pulmonary arterial blood pressure (Ppa) and in thickening of the pulmonary arterial medial layer in the rats. Three weeks after induction, acute administration of the MO extract to the rats decreased Ppa in a dose-dependent manner that reached statistical significance at a dose of 4.5 mg of freeze-dried extract per kg body weight. The reduction in Ppa suggested that the extract directly relaxed the pulmonary arteries. To assay the effects of chronic administration of the MO extract on PH, control, MCT and MCT+MO groups were designated. Rats in the control group received a saline injection; the MCT and MCT+MO groups received MCT to induce PH. During the third week after MCT treatment, the MCT+MO group received daily i.p. injections of the MO extract (4.5 mg of freeze-dried extract/kg of body weight). Compared to the control group, the MCT group had higher Ppa and thicker medial layers in the pulmonary arteries. Chronic treatments with the MO extract reversed the MCT-induced changes. Additionally, the MCT group had a significant elevation in superoxide dismutase activity when normalized by the MO extract treatments. In conclusion, the MO extract successfully attenuated the development of PH via direct vasodilatation and a potential increase in antioxidant activity.

[Mercury in tree rings: Advances, problems and prospects]. / æ ‘æœ¨å¹´è½®æ±žè®°å½•: 进展、问题和展望.

As a highly biotoxic element, mercury (Hg) can be enriched by the food chain and has negative effect on ecosystems. Changes of Hg flux and reserves in forest have important effects on its biogeochemical cycle in forest ecosystem. Due to limitation of temporal and spatial monitoring, there is not comprehensive understanding on Hg distribution. Widely distributed trees can be used as effective bio-monitors and Hg records in tree rings can be used to study Hg temporal and spatial distribution. Hg accumulated by root, leaf, bark, and other tissues can be detained in bole and record environmental Hg variations. Therefore, historical Hg trends can be restructured by analyzing Hg concentration in tree rings and the biogeochemical characteristics can be understood with Hg isotope ratio. We reviewed the method of measurement of Hg concentration and isotope ratio and application of reconstruction using Hg concentration in tree ring. We suggested the great application potential of Hg isotope ratio in atmospheric Hg construction and biogeochemistry cycle and raised concerns in further studies.

AMP-activated protein kinase (AMPK) activators from Myristica fragrans (nutmeg) and their anti-obesity effect.

AMP-activated protein kinase (AMPK) is a potential therapeutic target for the treatment of metabolic syndrome including obesity and type-2 diabetes. As part of an ongoing search for new AMPK activators from plants, this study found that the total extract of Myristica fragrans (nutmeg) activated the AMPK enzyme in differentiated C2C12 cells. As active constituents, seven 2,5-bis-aryl-3,4-dimethyltetrahydrofuran lignans, tetrahydrofuroguaiacin B (1), saucernetindiol (2), verrucosin (3), nectandrin B (4), nectandrin A (5), fragransin C(1) (6), and galbacin (7) were isolated from this extract. Among the isolates, compounds 1, 4, and 5 at 5 microM produced strong AMPK stimulation in differentiated C2C12 cells. In addition, the preventive effect of a tetrahydrofuran mixture (THF) on weight gain in a diet-induced animal model was further examined. These results suggest that nutmeg and its active constituents can be used not only for the development of agents to treat obesity and possibly type-2 diabetes but may also be beneficial for other metabolic disorders.

AMP-activated protein kinase (AMPK) activation by benzofurans and coumestans isolated from Erythrina abyssinica.

AMP-activated protein kinase (AMPK) has been proposed as a therapeutic target for the treatment of metabolic syndrome including obesity and type-2 diabetes. The bioassay-guided fractionation of an EtOAc-soluble extract of the stem bark of Erythrina abyssinica led to the isolation of a new coumestan, erythribyssin N (1), and two new benzofurans, erythribyssin F (2) and erythribyssin H (3), along with five known compounds (4-8). When tested for their stimulatory effects on AMPK activity at a concentration of 10 muM, compounds 4 and 5 showed potent activation, while compounds 1, 2, and 7 had moderate effects. These results suggest that benzofurans and coumestans may be new lead compounds for regulating the AMPK enzyme.

Efficient synthesis and structural characteristics of zwitterionic twisted pi-electron system biaryls.

A series of unconventional twisted pi-electron system molecules has been synthesized via Suzuki cross-coupling of two sterically hindered arenes. Crystallographic analysis of these molecules reveals a large ring-ring dihedral twist angle (87 degrees ) and a highly charge-separated zwitterionic ground state. An efficient conversion of phenols into aryl halides is also reported. [reaction: see text]

Ultralarge hyperpolarizability twisted pi-electron system electro-optic chromophores: synthesis, solid-state and solution-phase structural characteristics, electronic structures, linear and nonlinear optical properties, and computational studies.

This contribution details the synthesis and chemical/physical characterization of a series of unconventional twisted pi-electron system electro-optic (EO) chromophores. Crystallographic analysis of these chromophores reveals large ring-ring dihedral twist angles (80-89 degrees) and a highly charge-separated zwitterionic structure dominating the ground state. NOE NMR measurements of the twist angle in solution confirm that the solid-state twisting persists essentially unchanged in solution. Optical, IR, and NMR spectroscopic studies in both the solution phase and solid state further substantiate that the solid-state structural characteristics persist in solution. The aggregation of these highly polar zwitterions is investigated using several experimental techniques, including concentration-dependent optical and fluorescence spectroscopy and pulsed field gradient spin-echo (PGSE) NMR spectroscopy in combination with solid-state data. These studies reveal clear evidence of the formation of centrosymmetric aggregates in concentrated solutions and in the solid state and provide quantitative information on the extent of aggregation. Solution-phase DC electric-field-induced second-harmonic generation (EFISH) measurements reveal unprecedented hyperpolarizabilities (nonresonant mubeta as high as -488,000 x 10(-48) esu at 1907 nm). Incorporation of these chromophores into guest-host poled polyvinylphenol films provides very large electro-optic coefficients (r(33)) of approximately 330 pm/V at 1310 nm. The aggregation and structure-property effects on the observed linear/nonlinear optical properties are discussed. High-level computations based on state-averaged complete active space self-consistent field (SA-CASSCF) methods provide a new rationale for these exceptional hyperpolarizabilities and demonstrate significant solvation effects on hyperpolarizabilities, in good agreement with experiment. As such, this work suggests new paradigms for molecular hyperpolarizabilities and electro-optics.

X-Shaped electro-optic chromophore with remarkably blue-shifted optical absorption. Synthesis, characterization, linear/nonlinear optical properties, self-assembly, and thin film microstructural characteristics.

A novel type of "X-shaped" two-dimensional electro-optic (EO) chromophore with extended conjugation has been synthesized and characterized. This chromophore is found to exhibit a remarkably blue-shifted optical maximum (357 nm in CH(2)Cl(2)) while maintaining a very large first hyperpolarizability (beta). Hyper-Rayleigh Scattering (HRS) measurements at 800 nm provide a beta(zzz) value of 1840 x 10(-30) esu. Self-assembled thin films of this chromophore were fabricated via a layer-by-layer chemisorptive siloxane-based approach. The chromophoric multilayers have been characterized by transmission optical spectroscopy, advancing contact angle measurements, synchrotron X-ray reflectivity, atomic force microscopy, and angle-dependent polarized second harmonic generation spectroscopy. The self-assembled chromophoric films exhibit a dramatically blue-shifted optical maximum (325 nm) while maintaining a large EO response (chi(2)(333) approximately 232 pm/V at 1064 nm; r(33) approximately 45 pm/V at 1310 nm). This work demonstrates an attractive approach to developing EO materials offering improved nonlinearity-transparency trade-offs.

Self-assembled electrooptic thin films with remarkably blue-shifted optical absorption based on an X-shaped chromophore.

An "X-shaped" two-dimensional electrooptic (EO) chromophore with extended orthogonal conjugation was designed and synthesized. Self-assembled thin films of this chromophore were fabricated via layer-by-layer chemisorptive siloxane-based self-assembly. The films exhibit a dramatically blue-shifted optical maximum (325 nm) while maintaining a large EO response (chi33(2) approximately 232 pm/V at 1064 nm; r33 approximately 43 pm/V at 1550 nm).

Vapor phase self-assembly of electrooptic thin films via triple hydrogen bonds.

The donor-acceptor pi-electron chromophore 5-{4-[2-(4,6-diamino-[1,3,5]triazin-2-yl)-vinyl]-benzylidene}-pyrimidine-2,4,6-trione (DTPT) was designed and synthesized. Triple H-bonding interactions between neighboring molecules direct self-assembled chromophore alignment in a head-to-tail orientation using a straightforward vapor phase deposition process. Angle-dependent SHG interference patterns and the quadratic dependence of the 532 nm light output intensity on the thickness of the DTPT films for glass substrates coated on both sides demonstrate high, reproducible film quality and uniformity. XRD also demonstrates long-range order in the film and yields a molecular tilt angle in good agreement with polarized SHG data, clearly showing that out-of-plane ordering of chromophore molecules has been achieved.