Thioredoxin-1 promotes the restoration of alveolar bone in periodontitis with diabetes.

Treatment of periodontitis in people with diabetes remains challenging. The present study aimed to investigate the therapeutic potential of thioredoxin-1 (TRX1) in periodontitis with diabetes, as well as its role in modulating osteogenic differentiation. Our findings indicated that the production of reactive oxygen species (ROS) was elevated, while the expression of TRX1 was significantly reduced in the periodontal tissues of periodontitis mice with diabetes. Furthermore, knockdown of TRX1 in periodontal ligament stem cells (PDLSCs) resulted in the inhibition of osteogenic differentiation through disrupting Wnt/ß-catenin signaling. However, this inhibition was restored upon administration of recombinant human TRX1 (rhTRX1). Importantly, rhTRX1 treatment decreased ROS generation, activated Wnt/ß-catenin signal pathway and considerably promoted the alveolar bone repair of periodontitis mice with diabetes. These findings highlighted the crucial protective role of TRX1 in periodontitis with diabetes and suggested that it may serve as a potential therapeutic target for refractory periodontitis associated with oxidative stress.

Exploration of the shared gene signatures and molecular mechanisms between periodontitis and inflammatory bowel disease: evidence from transcriptome data.

Background: Periodontitis disease (PD) is associated with a systemic disorder of inflammatory bowel disease (IBD). The immune response is the common feature of the two conditions, but the more precise mechanisms remain unclear. Methods: Differential expressed genes (DEGs) analysis and weighted gene co-expression network analysis (WGCNA) were performed on PD and Crohn's disease (CD) data sets to identify crosstalk genes linking the two diseases. The proportions of infiltrating immune cells were calculated by using Single-sample Gene Set Enrichment Analysis. In addition, a data set of isolated neutrophils from the circulation was performed via WGCNA to obtain PD-related key modules. Then, single-cell gene set enrichment scores were computed for the key module and grouped neutrophils according to score order in the IBD scRNA-seq data set. Single-cell gene enrichment analysis was used to further explore the biological process of the neutrophils. Results: A total of 13 crosstalk genes (IL1B, CSF3, CXCL1, CXCL6, FPR1, FCGR3B, SELE, MMP7, PROK2, SRGN, FCN1, TDO2 and CYP24A1) were identified via DEGs analysis and WGCNA by combining PD and CD data sets. The enrichment analysis showed that these genes were involved in interleukin-10 signaling and inflammatory response. The immune infiltration analysis showed a significant difference in the proportion of neutrophils in PD and CD compared with healthy patients. Neutrophils were scored based on the expression of a periodontitis-related gene set in the scRNA-seq data set of IBD. The enrichment analysis demonstrated that inflammatory response, TNFα signaling via NF-κB and interferon-gamma response were upregulated in the high-score group, which expressed more pro-inflammatory cytokines and chemokines compared with the low-score group. Conclusions: This study reveals a previously unrecognized mechanism linking periodontitis and IBD through crosstalk genes and neutrophils, which provides a theoretical framework for future research.

A Nanoconfined Water-Ion Coordination Network for Flexible Energy-Dissipation Devices.

Water-ion interaction in a nanoconfined environment that deeply constrains spatial freedoms of local atomistic motion with unconventional coupling mechanisms beyond that in a free, bulk state is essential to spark designs of a broad spectrum of nanofluidic devices with unique properties and functionalities. Here, it is reported that the interaction between ions and water molecules in a hydrophobic nanopore forms a coordination network with an interaction density that is nearly fourfold that of the bulk counterpart. Such strong interaction facilitates the connectivity of the water-ion network and is uncovered by corroborating the formation of ion clusters and the reduction of particle dynamics. A liquid-nanopore energy-dissipation system is designed and demonstrated in both molecular simulations and experiments that the formed coordination network controls the outflow of confined electrolytes along with a pressure reduction, capable of providing flexible protection for personnel and devices and instrumentations against external mechanical impact and attack.

TRAF-STOP alleviates osteoclastogenesis in periodontitis.

The enhanced osteoclastogenesis contributes to alveolar bone resorption in periodontitis, which increases the risk of tooth loss. To reduce bone destruction, the inhibition of osteoclast development is proposed as a feasible treatment. CD40L-CD40-TRAF6 signal transduction plays a crucial role in inflammation, but how it regulates osteoclast activity in periodontitis has not been elucidated. In this study, we showed the potential role of CD40L-CD40-TRAF6 signaling in periodontitis. CD40L obviously promoted osteoclast formation and bone resorption capacity in vitro. Mechanistically, we found that osteoclastogenesis was enhanced by the overexpression of NFATc1 and NF-κB activation. Importantly, osteoclast activity was effectively suppressed by TRAF-STOP, a small molecular inhibitor of TRAF6. Furthermore, local injection of TRAF-STOP-loaded injectable PLGA-PEG-PLGA hydrogel could alleviate ligation-induced periodontitis in vivo. Taken together, TRAF-STOP shows promising clinical efficacy in periodontitis through alleviating osteoclastogenesis.

Tuning Proapoptotic Activity of a Phosphoric-Acid-Tethered Tetraphenylethene by Visible-Light-Triggered Isomerization and Switchable Protein Interactions for Cancer Therapy.

We herein report a phosphoric-acid-substituted tetraphenylethene (T-P) capable of adapting its geometric configuration and biological activity to the microenvironment upon light irradiation for apoptosis modulation. Different from most ultraviolet-responsive isomerization, T-P undergoes cis-trans isomerization under visible light irradiation, which is biocompatible and thus photo-modulation is possible in living biosystems. By using alkaline phosphatase (ALP) and albumin as dual targets, T-P isomers display different protein binding selectivity, cancer-cell internalization efficiency and apoptosis-inducing ability. The proapoptotic activity was found to be kinetically controlled by the enzymatic reaction with ALP and regulated by co-existing albumin. Motivated by these findings, two-way modulation of proapoptotic effect and on-demand boosting anticancer efficacy were realized in vitro and in vivo using light and endogenous proteins as multiple non-invasive switching stimuli.

Expression of a phenoloxidase cascade inhibitor enhances the virulence of the fungus Beauveria bassiana against the insect Helicoverpa armigera.

Entomopathogenic fungi have high potential for controlling insect pests, although the slow killing speed has blocked their widespread application. To increase the virulence of entomopathogenic fungi, genetic modification can be employed. Egf1.0 is an immunosuppressive protein encoded by polydnavirus, carried by parasitoid wasp Microplitis demolitor, which blocks the prophenoloxidase (PPO) activation response of host insects. In this study, we explored the feasibility of genetically modifying entomopathogenic fungi with increased virulence by expressing Egf1.0. In comparison with the wild-type parents, the median lethal concentration (LC50) of Beauveria bassiana expressing Egf1.0 against Helicoverpa armigera was reduced by 2.7-fold, and the median lethal time (LT50) was reduced by 22.8%. In vitro assay showed that recombinant Egf1.0 was able to inhibit the PPO activation response of H. armigera. In vivo assay revealed that the expression of Egf1.0 in B. bassiana caused a higher degree of suppression to PPO activation response of H. armigera. These assays suggested that the increased virulence of the transgenic fungi is due to the increased ability to suppress the host insect's immune response. Moreover, colony growth, conidia yield, and germination assays revealed that the expression of Egf1.0 in B. bassiana had no effect on its growth and development. In conclusion, the expression of Egf1.0 can significantly enhance the pathogenicity of B. bassiana against host insects.

Polydatin attenuates renal fibrosis in diabetic mice through regulating the Cx32-Nox4 signaling pathway.

We previously found that polydatin could attenuate renal oxidative stress in diabetic mice and improve renal fibrosis. Recent evidence shows that NADPH oxidase 4 (Nox4)-derived reactive oxygen species (ROS) contribute to inflammatory and fibrotic processes in diabetic kidneys. In this study we investigated whether polydatin attenuated renal fibrosis by regulating Nox4 in vitro and in vivo. In high glucose-treated rat glomerular mesangial cells, polydatin significantly decreased the protein levels of Nox4 by promoting its K48-linked polyubiquitination, thus inhibited the production of ROS, and eventually decreasing the expression of fibronectin (FN) and intercellular adhesion molecule-1 (ICAM-1), the main factors that exacerbate diabetic renal fibrosis. Overexpression of Nox4 abolished the inhibitory effects of polydatin on FN and ICAM-1 expression. In addition, the expression of Connexin32 (Cx32) was significantly decreased, which was restored by polydatin treatment. Cx32 interacted with Nox4 and reduced its protein levels. Knockdown of Cx32 abolished the inhibitory effects of polydatin on the expression of FN and ICAM-1. In the kidneys of streptozocin-induced diabetic mice, administration of polydatin (100 mg·kg-1·d-1, ig, 6 days a week for 12 weeks) increased Cx32 expression and reduced Nox4 expression, decreased renal oxidative stress levels and the expression of fibrotic factors, eventually attenuating renal injury and fibrosis. In conclusion, polydatin promotes K48-linked polyubiquitination and degradation of Nox4 by restoring Cx32 expression, thereby decreasing renal oxidative stress levels and ultimately ameliorating the pathological progress of diabetic renal fibrosis. Thus, polydatin reduces renal oxidative stress levels and attenuates diabetic renal fibrosis through regulating the Cx32-Nox4 signaling pathway.

Reconstructed Order Analysis-Based Vibration Monitoring under Variable Rotation Speed by Using Multiple Blade Tip-Timing Sensors.

On-line vibration monitoring is significant for high-speed rotating blades, and blade tip-timing (BTT) is generally regarded as a promising solution. BTT methods must assume that rotating speeds are constant. This assumption is impractical, and blade damages are always formed and accumulated during variable operational conditions. Thus, how to carry out BTT vibration monitoring under variable rotation speed (VRS) is a big challenge. Angular sampling-based order analyses have been widely used for vibration signals in rotating machinery with variable speeds. However, BTT vibration signals are well under-sampled, and Shannon's sampling theorem is not satisfied so that existing order analysis methods will not work well. To overcome this problem, a reconstructed order analysis-based BTT vibration monitoring method is proposed in this paper. First, the effects of VRS on BTT vibration monitoring are analyzed, and the basic structure of angular sampling-based BTT vibration monitoring under VRS is presented. Then a band-pass sampling-based engine order (EO) reconstruction algorithm is proposed for uniform BTT sensor configuration so that few BTT sensors can be used to extract high EOs. In addition, a periodically non-uniform sampling-based EO reconstruction algorithm is proposed for non-uniform BTT sensor configuration. Next, numerical simulations are done to validate the two reconstruction algorithms. In the end, an experimental set-up is built. Both uniform and non-uniform BTT vibration signals are collected, and reconstructed order analysis are carried out. Simulation and experimental results testify that the proposed algorithms can accurately capture characteristic high EOs of synchronous and asynchronous vibrations under VRS by using few BTT sensors. The significance of this paper is to overcome the limitation of conventional BTT methods of dealing with variable blade rotating speeds.

Zincke's Salt-Substituted Tetraphenylethylenes for Fluorometric Turn-On Detection of Glutathione and Fluorescence Imaging of Cancer Cells.

In this paper, we report Zincke's salt-substituted tetraphenylethylenes 1a and 1b with Cl- and PF6- as counteranions, respectively. The crystal structure of 1b was determined. Both 1a and 1b are almost nonemissive even in the aggregated states. This is attributed to the photoinduced electron transfer from 2,2-bis(4-methoxyphenyl)-1-phenylvinyl-phenyl unit to 1-(2,4-dinitrophenyl) pyridinium unit within 1a and 1b. The results demonstrate that the emissions of 1a and 1b in aqueous solution can be switched on upon either reaction with GSH or light irradiation. On the basis of the reaction between 1a and GSH, 1a can be utilized for the fluorescence turn-on detection of GSH selectively, and GSH with concentration as low as 36.9 nM can be detected. The transformation of 1b into 2 under light irradiation results in the fluorescence imaging of Hela and U2OS cells and phototoxicity toward Hela and U2OS cells after the protonation of pyridine unit in 2 because of the acidic environment of tumor cells. Aggregates of 1b can be up-taken by Hela and U2OS cells and fluorescence imaging has been successfully recorded with CLSM. Moreover, the protonated form of 2 can function as photosensitizer and 1b shows phototoxicity toward tumor cells such as Hela and U2OS cells.

The entomopathogenic fungus Nomuraea rileyi impairs cellular immunity of its host Helicoverpa armigera.

In this study, we investigated the effect of the entomopathogenic fungus Nomuraea rileyi on Helicoverpa armigera cellular immune responses. Nomuraea rileyi infection had no effect on total hemocyte count (THC), but impaired hemocyte-mediated phagocytosis, nodulation, and encapsulation responses. Nomuraea rileyi infection led to a significant reduction in hemocyte spreading. An in vitro assay revealed that plasma from N. rileyi infected H. armigera larvae suppressed the spreading ability of hemocytes from naïve larvae. We infer that N. rileyi suppresses the cellular immune response of its host, possibly by secreting exogenous, cytotoxic compounds into the host's hemolymph.

Introductory lecture: recent research progress on aggregation-induced emission.

Since the discovery of the aggregation-induced emission (AIE) phenomenon in 2001, research on AIE molecules has drawn much attention, and this area has been expanding tremendously. This brief review will focus on recent advances in the science and application of AIE molecules, including new mechanistic understanding, new AIE molecules for sensing and imaging, stimuli-responsive AIE molecules and applications of AIE molecules for OLEDs. Moreover, this review will give a perspective on the possible opportunities and challenges that exist in the future for this area.

Bio-/Chemosensors and Imaging with Aggregation-Induced Emission Luminogens.

Aggregation-induced emission (AIE) luminogens show abnormal fluorescent behavior; they are non-emissive in solution, but they become strongly emissive after aggregation. Sensing and imaging are the major applications of AIE luminogens. By properly manipulating the aggregation and deaggregation of AIE molecules, various bio-/chemosensors have been developed. Moreover, AIE molecules with targeting groups have been devised for imaging of organelles and cancer cells. In this account, we report our recent work on the application of AIE luminogens for the construction of bio-/chemosensors and imaging.

Low-frequency transcranial magnetic stimulation is beneficial for enhancing synaptic plasticity in the aging brain.

In the aging brain, cognitive function gradually declines and causes a progressive reduction in the structural and functional plasticity of the hippocampus. Transcranial magnetic stimulation is an emerging and novel neurological and psychiatric tool used to investigate the neurobiology of cognitive function. Recent studies have demonstrated that low-frequency transcranial magnetic stimulation (≤1 Hz) ameliorates synaptic plasticity and spatial cognitive deficits in learning-impaired mice. However, the mechanisms by which this treatment improves these deficits during normal aging are still unknown. Therefore, the current study investigated the effects of transcranial magnetic stimulation on the brain-derived neurotrophic factor signal pathway, synaptic protein markers, and spatial memory behavior in the hippocampus of normal aged mice. The study also investigated the downstream regulator, Fyn kinase, and the downstream effectors, synaptophysin and growth-associated protein 43 (both synaptic markers), to determine the possible mechanisms by which transcranial magnetic stimulation regulates cognitive capacity. Transcranial magnetic stimulation with low intensity (110% average resting motor threshold intensity, 1 Hz) increased mRNA and protein levels of brain-derived neurotrophic factor, tropomyosin receptor kinase B, and Fyn in the hippocampus of aged mice. The treatment also upregulated the mRNA and protein expression of synaptophysin and growth-associated protein 43 in the hippocampus of these mice. In conclusion, brain-derived neurotrophic factor signaling may play an important role in sustaining and regulating structural synaptic plasticity induced by transcranial magnetic stimulation in the hippocampus of aging mice, and Fyn may be critical during this regulation. These responses may change the structural plasticity of the aging hippocampus, thereby improving cognitive function.

Highly solid-state emissive pyridinium-substituted tetraphenylethylene salts: emission color-tuning with counter anions and application for optical waveguides.

In this paper seven salts of pyridinium-substituted tetraphenylethylene with different anions are reported. They show typical aggregation-induced emission. Crystal structures of three of the salts with (CF(3)SO(2))(2) N(-), CF(3) SO(3)(-), and SbF(6)(-) as the respective counter anions, are determined. The emission behavior of their amorphous and crystalline solids is investigated. Both amorphous and crystalline solids, except for the one with I(-), are highly emissive. Certain amorphous solids are red-emissive with almost the same quantum yields and fluorescence life-times. However, some crystalline solids are found to show different emission colors varying from green to yellow. Thus, their emission colors can be tuned by the counter anions. Furthermore, certain crystalline solids are highly emissive compared to the respective amorphous solids. Such solid-state emission behavior of these pyridinium-substituted tetraphenylethylene salts is interpreted on the basis of their crystal structures. In addition, optical waveguiding behavior of fabricated microrods is presented.

Enhancing the activity and tuning the mechanism of formic acid oxidation at tetrahexahedral Pt nanocrystals by Au decoration.

Tetrahexahedral Pt nanocrystals (THH Pt NCs), bound by high index facets, belong to an emerging class of nanomaterials that promise to bridge the gap between model and practical electrocatalysts. The atomically stepped surfaces of THH Pt NCs are extremely active for the electrooxidation of small organic molecules but they also readily accommodate the dissociative chemisorption of such species, resulting in poisoning by strongly adsorbed CO. Formic acid oxidation is an ideal reaction for studying the balance between these competing catalyst characteristics, since it can proceed by either a direct or a CO mediated pathway. Herein, we describe electrochemical and in situ FTIR spectroscopic investigations of formic acid electrooxidation at both clean and Au adatom decorated THH Pt NC surfaces. The Au decoration leads to higher catalytic currents and enhanced CO(2) production in the low potential range. As the CO oxidation behaviour of the catalyst is not improved by the presence of the Au, it is likely that the role of the Au is to promote the direct pathway. Beyond their fundamental importance, these results are significant in the development of stable, poison resistant anodic electrocatalysts for direct formic acid fuel cells.

Functional bundles of the medial patellofemoral ligament.

The purpose of this study was to explore the anatomy and evaluate the function of the medial patellofemoral ligament (MPFL). Anatomical dissection was performed on 12 fresh-frozen knee specimens. The MPFL is a condensation of capsular fibers, which originates at the medial femoral condyle. It runs transversely and inserts to the medial edge of the patella. With the landmark of the medial femur epicondyle (MFE), the femoral origination was located: just 8.90 ± 3.27 mm proximally and 13.47 ± 3.68 mm posteriorly to the MFE. The most interesting finding in present study was functional bundles of its patellar insertion. Approximately from the femoral origination point, fibers of the MPFL form two relatively concentrated fiber bundles: the inferior-straight bundle and the superior-oblique bundle. The whole length of each was 71.78 ± 5.51 and 73.67 ± 5.40 mm, respectively. The included angle between bundles was 15.1° ± 2.1°. Although the superior-oblique bundle and the inferior-straight bundle run on the patellar MPFL inferiorly and superiorly, respectively, as their name indicates, the two bundles are not entirely separated, which make MPFL one intact structure. The inferior-straight bundle is the main static soft tissue restraints where the superior-oblique bundle associated with vastus medialis obliquus (VMO) is to serve as the main dynamic soft tissue restraints. So this finding may provide the theoretical foundation for the anatomical reconstruction of the MPFL and shed lights on the future researchers.