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Doxorubicin (DOX) is a highly effective anticancer anthracycline drug, but its side effects at the level of the heart has limited its widespread clinical application. Melatonin is a documented potent antioxidant, nontoxic and cardioprotective agent, and it is involved in maintaining mitochondrial homeostasis and function. The present study established acute DOX-induced cardiotoxicity models in both H9c2 cells incubated with 1 μM DOX and C57BL/6 mice treated with DOX (20 mg/kg cumulative dose). Melatonin markedly alleviated the DOX-induced acute cardiac dysfunction and myocardial injury. Both in vivo and in vitro studies verified that melatonin inhibited DOX-induced mitochondrial dysfunction and morphological disorders, apoptosis, and oxidative stress via the activation of AMPK and upregulation of PGC1α with its downstream signaling (NRF1, TFAM and UCP2). These effects were reversed by the use of AMPK siRNA or PGC1α siRNA in H9c2 cells, and were also negated by the cotreatment with AMPK inhibitor Compound C in vivo. Moreover, PGC1α knockdown was without effect on the AMPK phosphorylation induced by melatonin in the DOX treated H9c2 cells. Therefore, AMPK/PGC1α pathway activation may represent a new mechanism for melatonin exerted protection against acute DOX cardiotoxicity through preservation of mitochondrial homeostasis and alleviation of oxidative stress and apoptosis.

Background The incidence of myasthenia gravis (MG) is increasing, and its characteristics in elderly patients are believed to differ from those in younger patients. However, only a few studies have focused on elderly patients with MG. Objective To review the characteristics of MG in elderly patients and evaluate whether older age is an independent factor associated with achieving minimal manifestation status (MMS). Methods This retrospective cohort study included 367 patients (319 non-elderly and 48 elderly patients) with MG enrolled at Xiangya Hospital from September 1, 2016, to December 31, 2018. We collected demographic data and information regarding comorbidities, antibody status, Myasthenia Gravis Foundation of America classification, affected muscle groups, thymoma, and treatment. MMS was defined as the primary outcome. Results Comorbidities were more common in elderly than in younger patients with MG. Anti-acetylcholine receptor antibody was the dominant subtype, whereas anti-muscle-specific tyrosine kinase antibody was rare and detected only in non-elderly patients. Elderly patients were more likely than younger patients to have generalized MG, but the frequency of thymoma was lower (28.5% vs. 10.4%, p = 0.0078). MMS or better was achieved in 154 (48.3%) and 13 (27.1%) non-elderly and elderly patients, respectively. Older age did not appear to be an independent factor associated with MMS (hazard ratio = 0.625; 95% confidence interval, 0.345-1.131). Conclusions Older age was not an independent factor for a worse prognosis in patients with MG. The treatment of elderly patients with MG should be individually tailored.

During the long-term service life of hydraulic structures, the calcium compounds in cement-based materials decompose in the aqueous environment, leading to the continuous change of seepage characteristics. To study the influence of calcium leaching on the concrete dam seepage characteristics, we proposed a new mathematic model of the cement-based material calcium leaching model under advection-diffusion-driven leaching. A solid-liquid nonequilibrium model is adopted to model the decomposition of calcium hydroxide (CH) and calcium silicate hydrate gel (C-S-H). To calculate the porosity more accurately, the proposed model takes the effect of different calcium compound decomposition on the porosity increase in consideration, respectively. Shimantan dam is selected for the three-dimensional (3D) calcium leaching analyses. The 3D finite element model of this dam is analyzed using COMSOL Multiphysics software that is based on the finite element method. Based on the proposed model, seepage characteristics evolutions of the Shimantan dam are studied. Good agreement between the numerical results and the monitored data indicates the accuracy of this simulation. The result shows that after 100 a leaching duration, the uplift pressure increases by 40.8%, and the leakage quantities of the dam body and foundation increase by 48 and 17 times. The rise of uplift pressure and leakage changes caused by curtain deterioration are the main influences of calcium leaching on the dam seepage. The parameter sensitivity results show that it is necessary to reduce CH content in cement-based materials to obtain better calcium leaching durability. This model and simulation results can guide the operation of concrete dams under advection-diffusion-driven leaching.

Bacterial infections on implantable materials can cause severe complications for affected patients, posing a serious threat to human health. Therefore, the development of appropriate surface modification strategies to construct the antibacterial platforms on medical implants are urgently needed. In this work, the poly(vinyl alcohol) (PVA)-stabilized polypyrrole nanoparticles (PVA-PPy NPs) were prepared by oxidative polymerization using FeCl

Toll-like receptors (TLRs) play an important role in innate immune through recognizes pathogens. In order to reveal the evolutionary patterns and adaptive evolution of avian TLRs, we examined 66 representative bird species in 26 orders. Phylogenetic results indicated that TLR1A and TLR1B may have differentiated functionally. Evolutionary analysis showed that the TLR genes in birds under strong Purification selection (0.165-0.4265). A total of 126 common positively selected codons were identified in 10 TLR genes of avian, and most sites were located in the extracellular leucine-rich repeat (LRR) functional domains, and both environment and feeding habits were external factors driving the evolution of avian TLR genes. Environmental pressures had a greater effect on TLR1B, TLR2B, TLR3 and TLR4, while feeding habits were active in affecting TLR2A, TLR2B, TLR15 and TLR21. Our data suggested that TLR genes have been subjected to different selective pressures in the diversification of birds and that these changes enabled them to respond differently to pathogens from diverse sources.

Surfactant protein B (SP-B) deficiency is an autosomal recessive disorder that impairs surfactant homeostasis and manifests as lethal respiratory distress. A compelling argument exists for gene therapy to treat this disease, as de novo protein synthesis of SP-B in alveolar type 2 epithelial cells is required for proper surfactant production. Here we report a rationally designed adeno-associated virus (AAV) 6 capsid that demonstrates efficiency in lung epithelial cell transduction based on imaging and flow cytometry analysis. Intratracheal administration of this vector delivering murine or human proSFTPB cDNA into SP-B deficient mice restores surfactant homeostasis, prevents lung injury, and improves lung physiology. Untreated SP-B deficient mice develop fatal respiratory distress within two days. Gene therapy results in an improvement in median survival to greater than 200 days. This vector also transduces human lung tissue, demonstrating its potential for clinical translation against this lethal disease., Surfactant protein B (SP-B) deficiency is a genetic lung disease that results in lethal respiratory distress within months of birth. Here, the authors describe a gene therapy strategy using a rationally designed AAV6 capsid that restores surfactant homeostasis, prevents lung injury, and improves survival in a mouse model of SP-B deficiency.

BACKGROUND: We investigated the correlation between glucose metabolism patterns of different immune cells and the metabolic regulatory signaling pathways in myasthenia gravis (MG) and aimed to identify therapeutic targets for MG. METHODS: We isolated peripheral blood mononuclear cells (PBMCs) and sorted CD19(+)B cells, dendritic cells (DCs), CD4(+) T cells, CD8(+) T cells, CD4(+)CD25(+) regulatory T cells (Tregs), CD4(+)CD25(−)T cells, and T helper (Th) cells such as Th1, Th2, and Th17 cells. Then, we detected the expression levels of PI3K/AKT/mTOR-HIF-1α, GLUT1, hexokinase (HK), phosphofructokinase (PFK), and pyruvate kinase (PK) by RT-PCR, measured the oxygen consumption rate and extracellular acidification rate of ex vivo freshly sorted cells using the Seahorse XF(e)96 Analyzer. In addition, we compared the glycolysis levels using these cells from the same MG patients. By performing in vitro experiments, we measured, the mRNA expression levels of mTOR, HIF-1α, B cell activating factor receptor (BAFF-R), GLUT1, HK, PFK, and PK, in addition to ECAR profiles, frequency of CD80 and CD86, and IgG levels from the culture supernatant of B cells (isolated from MG patients) treated with rapamycin and PX-478 (selective mTOR and HIF-1α inhibitor, respectively) from. RESULTS: Except PBMCs, Th2 and CD8(+) T cells, the expression levels of the key enzymes involved in glycolysis and HIF-1α were significantly higher in B cells, DCs, Tregs, CD4(+)CD25(−)T cells, and Th1 and Th17 cells in MG patients, and the measurement of ECAR and OCR confirmed the metabolic status. In MG patients, B cells and DCs showed significantly higher levels of glycolysis and glycolytic capacity than CD8(+) T cells, CD4(+) T cells and its subsets. In vitro, except IgG levels, the increased glycolysis levels, expression of key glycolytic enzymes, BAFF-R and frequency of CD80 and CD86 of B cells, could be inhibited by rapamycin and PX-478. CONCLUSIONS: Different subtypes of immune cells in MG exhibit different glucose metabolism patterns. The mTOR-HIF-1α signaling pathway might be the immunometabolism reprogramming checkpoint of glycolysis-dependent activated B cells in MG.

In research using heat tracing technology to investigate the lateral hyporheic exchange in the shallow geological body of the riparian zone, the accurate estimation of temperature changes can provide a scientific basis for quantifying the process of lateral hyporheic exchange. To improve the accuracy of estimating temperature changes in the riparian zone, a hydrothermal coupling model considering parameter heterogeneity was established based on existing models of the relationship between thermal conductivity and saturation. The model was verified by temperature data from laboratory experiments, and the effect of the thermal conductivity prediction models was compared with that of the partial differential equation (PDE) modeling approach. The results show that the established hydrothermal coupling model can effectively characterize the temperature changes observed in a generalized laboratory model of the riparian zone, and the model simulation effects vary with the equivalent thermal conductivity models. In addition, several thermal conductivity empirical models are suggested for further application. The model parameter sensitivity analysis indicated that the hydraulic conductivity ks, VG model parameters (α and β) and heat capacity of soil Cs have a relatively large effect on the temperature output of the model. The results of this study will provide reference for the selection of equivalent thermal conductivity model for simulating temperature variations in the riparian zone.

Recent studies have suggested that genomic diversity may play a key role in different clinical outcomes, and the importance of SNPs is becoming increasingly clear. In this article, we summarize the bioactivity of SNPs that may affect the sensitivity to or possibility of drug reactions that occur among the signaling pathways of regularly used immunosuppressants, such as glucocorticoids, azathioprine, tacrolimus, mycophenolate mofetil, cyclophosphamide and methotrexate. The development of bioinformatics, including machine learning models, has enabled prediction of the proper immunosuppressant dosage with minimal adverse drug reactions for patients after organ transplantation or for those with autoimmune diseases. This article provides a theoretical basis for the personalized use of immunosuppressants in the future.

Self-healing hydrogels possess the capability to repair themselves after mechanical damage, but their applications are often severely limited by their weak mechanical strengths or poor healing efficiencies. To obtain the self-healing hydrogels with high performances, a linear polysaccharide template with aldehyde groups was introduced in the gelation process. The polysaccharide template (oxidized sodium alginate, OSA) can conjugate with acrylamide (AM) monomer via Schiff base reaction. The radical polymerization between double bonds in the side chains of OSA and free AM monomer results in the formation of OSA-poly(acrylamide) (OSA-PAM) hydrogels. The synergistic effect of dynamic Schiff base and hydrogen bonding interactions between OSA and PAM chains endows the OSA-PAM hydrogels with excellent self-healing and mechanical properties. The resulting OSA-PAM hydrogels also exhibit controllable conductivity and stretch sensitivity. The self-healing, mechanically tough and conductive OSA-PAM hydrogels could have potential applications in artificial skins, robotic actuators and medical devices.

Controlled architecture of bifunctional polymers on surfaces is highly challenged because of the stringent reaction conditions or tedious operations required for surface modification. Herein, a simple and effective method was developed to assemble zwitterionic and cationic binary polymer brushes onto polydopamine-anchored stainless steel (SS) surfaces. Zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) was first graft polymerized from the functionalized SS surface via thiol–ene “click” reaction. Alkynyl-modified cationic poly(2-(methacryloyloxy) ethyl trimethylammonium chloride) (alkynyl-PMETA) was subsequently introduced via azide–alkyne “click” reaction. After the grafting of PMPC/PMETA binary polymer brushes, the resulting functionalized SS surfaces can cooperatively reduce the adhesion of Gram-positive bacteria Staphylococcus aureus (S. aureus) and Gram-negative bacteria Pseudomonas sp., as well as the attachment of microalgae Amphora coffeaeformis. In addition, the binary polymer brus...

Severe medical device-associated infections caused by pathogenic bacteria have become an immediate threat to global public health, mainly because of the development of multiple drug resistance (MDR). Relevant design of functionalized biomaterials are thus essential to remit or mitigate the medical device-associated infections. In the present work, we developed a strategy of combining antifouling and photothermal therapy (PTT) in a single platform for antibacterial applications. The polydimethylsiloxane (PDMS) surface was modified with poly(ethylene glycol) (PEG) and tannic acid-reduced gold nanoparticles (Au@TA NPs) for better photothermal and antifouling performance. PEG facilitates the rapid self-assembly of Au@TA NPs on the surface to form a stable Au@TA NPs/PEG (TA-PEG-Au) layer. The functionalized surface with antifouling and antibacterial properties arise from the inherent fouling resistance of PEG and photothermal conversion of Au NPs. The TA-PEG-Au coating exhibits remarkable antifouling performance to bacterial adhesion and excellent antibacterial property under near-infrared (NIR) irradiation both in vitro and in vivo. The antibacterial TA-PEG-Au coatings also show low cytotoxicity. The present work provides an efficient strategy for the design of high-performance antifouling and antibacterial materials to fight against medical device-associated infections.

In this Letter, we propose a type of continuous phase vortex gratings (CPVGs), which are able to generate a series of vortex beams with equal or proportional diffracted energies and different topological charges (TCs). A set of CPVGs with dimensions (60 × 60 × 1.1 μm3) are directly designed by mathematical equations, which avoids the use of iterative algorithms. The CPVGs are fabricated by femtosecond laser direct writing (FsLDW) with photoresist, and the experimentally generated vortex beams are in good agreement with the theoretical designs, exhibiting high optical efficiencies. In addition, we realized a CPVG onto the tip of a composite fiber for integrated optical systems. Our work paves the way for applications in optical communications, optical manipulations, and high-performance integrated optics.

Poly-ether-ether-ketone (PEEK) is a promising material in oral repair and orthopedic implantation field due to its stability and proper elastic modulus. However, the lack of simple but effective strategy to functionalize PEEK and improve its antibacterial function hinders its further biomedical application. In this study, a sulfonated 3D porous PEEK is fabricated via sulfonation treatment, and then decorated with the in situ synthesized zeolitic imidazolate framework-8 (ZIF-8), in which Ag+ ions were loaded with high loading capacity. Surface morphology, roughness, chemical composition and hydrophilicity of all the substrates were evaluated in details, suggesting Ag+ ions loaded ZIF-8 on sulfonated PEEK (SPZA) was successfully prepared. The antibacterial activity of pristine and functionalized PEEK was evaluated by inhibition zone test, spread plate assay, growth curve, and morphology of bacteria. Experimental results demonstrate that the SPZA has effectively bacteriostatic performance against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The excellent antimicrobial activity is attributed to the synergistic effect of Ag+ and Zn2+ ions released continuously from SPZA. This work provides a promising route for surface modification of PEEK and offer a potential candidate for biomedical implants.

Ruthenium (Ru) complexes have been extensively studied for their potential use as DNA structural probes, cellular imaging agents and anticancer drugs due to their favorable photochemistry and photobiological properties. Here, we have synthesized three water-soluble nitrosylruthenium [(CH3)4N][RuCl3(QN)(NO)] complexes using 8-hydroxyquinoline (Hhqn) and its derivatives (2-methyl-8-quinolinoline [H2mqn] and 2-cholo-8-quiolinoline [H2cqn]) as ligands (QN = hqn, 2mqn or 2cqn); their structures were confirmed with X-ray crystal diffraction. The [RuCl3(2cqn)(NO)]− complex shows more activity than the other two complexes, with an IC50 value of 21.5 µM under light and of 100 µM without photoirradiation. The antiproliferative effects induced by the complex arrested the cell cycle at the G2/M phase. Furthermore, photo-controlled real-time NO release from the complexes was confirmed via spin trapping of NO free radicals. The photochemical DNA cleavage of the complexes was also demonstrated, possibly due to photo-induced free radicals. Moreover, the binding constants of the complexes with calf thymus DNA and human serum albumin were calculated by fluorescence spectroscopy to understand the effects of the substituent groups on the biological activity. The [RuCl3(2cqn)(NO)]− complex had the highest binding constant, consistent with its high cytotoxicity. Thus, we developed an effective and simple method to control cytotoxic activities using photoactive [RuCl3(QN)(NO)]− complexes, which has potential therapeutic applications in medicine and biological science.

The B-lymphocyte-induced maturation protein 1 (Blimp1) regulates T-cell homeostasis and function. Loss of Blimp1 could double the proportion of follicular regulatory T (Tfr) cells. However, the effects that Blimp1 may have on the function of Tfr cells remain unknown. Here we document the function for Blimp1 in Tfr cells in vitro and in vivo. Data presented in this study demonstrate that Tfr cells indirectly inhibit the activation and differentiation of B cells by negatively regulating follicular helper T cells, so lowering the secretion of antibody. Lack of Blimp1 makes the immune suppression function of Tfr cells impaired in vitro. In the in vivo study, adoptive transfer of Tfr cells could reduce immune responses in germinal centres and relieve the muscle weakness symptoms of mice with experimental autoimmune myasthenia gravis. Blimp1 deficiency resulted in reduced suppressive ability of Tfr cells. This study identifies that Tfr cells are potent suppressors of immunity and are controlled by Blimp1.

Abnormal CD4+T cell activation is known to play roles in the pathogenesis of myasthenia gravis (MG). However, little is known about the mechanisms underlying the roles of lncRNAs in regulating CD4+ T cell. In this study, we discovered that the lncRNA IFNG-AS1 is abnormally expressed in MG patients associated with quantitative myasthenia gravis (QMG) and the positive anti-AchR Ab levels patients. IFNG-AS1 influenced Th1/Treg cell proliferation and regulated the expression levels of their transcription factors in an experimental autoimmune myasthenia gravis (EAMG)model. IFNG-AS1 could reduce the expression of HLA-DRB and HLA-DOB and they had a negative correlation in MG. Furthermore IFNG-AS1 influenced the expression levels of CD40L and CD4+ T cells activation in MG patient partly depend on effecting the HLA-DRB1 expression. It suggests that IFNG-AS1 may be involved in CD4+T cell-mediated immune responses in MG.

Hydrogels have been considered as promising materials in tissue engineering and biomedical areas. However, the weak and brittle nature of common synthetic hydrogels largely hinders their potential applications. Therefore, it is challenging to fabricate tough hydrogels for biomedical applications. In this manuscript, well-defined and thermo-responsive polyurethane-poly(ethylene glycol) (PU-PEG) hydrogels were prepared via thermally-induced copper-catalyzed 1,3-dipolar azide-alkyne cycloaddition (CuAAC) using azido-pendent PU-PEG and dialkynyl PEG as the gel precursors. The physical properties of the as-formed hydrogels were investigated by swelling ratios and mechanical tests. The PU-PEG hydrogels not only possess thermo-responsive and excellent mechanical properties, but also exhibit good biocompatibility.

Nacre-like hybrid films based on N-succinyl chitosan (NSC), sodium alginate (SA) and lanthanide ions were fabricated via coordination interactions. In this work, the binary building blocks (NSC and SA) were self-assembled into aligned hydrogel films by coordination with lanthanide ions, and hierarchical NSC-SA hybrid films were obtained upon drying. Two species of lanthanide ions (Gd3+ and Yb3+) were used to fabricate the hierarchical NSC-SA hybrid films. The as-prepared NSC-SA hybrid films exhibit high tensile strength and stability. The tensile strength and toughness of as-prepared hybrid films reach 122.10MPa and 3.89MJm-3, respectively. Meanwhile, the well-aligned lamellar microstructures also exhibit a good light transmittance. The highest light transmittance reaches 92% for NSC-SA hybrid films at 760nm. This fabrication method for hierarchical NSC-SA hybrid films is innovative due to the utilization of rare earth coordination bonding, and can serve as the basic strategy for the construction of high-performance composites in the near future.

In this work, multifunctional B,N codoped carbon dots (B/N–C-dots) were synthesized from a facile hydrothermal treatment of branched polyethylenimine and 4-formylphenylboronic acid. The obtained B/N–C-dots had a very narrow size distribution and showed excitation-wavelength-dependent photoluminescence properties with a high fluorescence quantum yield (QY) of 15.85%. The B/N–C-dots showed temperature and pH (3–13) dual responses. Additionally, the B/N–C-dots showed a good sensitivity and selectivity to Fe3+ with a detection limit of 1.62 μM. What is more, the as-prepared B/N–C-dots exhibited low toxicity and good biocompatibility and could be used for cell imaging. Considering these good properties, the obtained B/N–C-dots have good potential for temperature, pH, and ion sensors and cellular imaging.

It is well-known that tannic acid (TA) and its analogs bind strongly to various substrates to produce, for example, the familiar and unpleasant “tea stains”. Functionalization of a polymer or macromolecule with TA would confer the resulting biomacromolecules with similar binding or anchoring ability on many surfaces. To verify the hypothesis, the naturally occurring polysaccharide agarose (Agr) was functionalized with alkyl bromo moieties, followed by etherification with tannic acid under basic conditions via Williamson ether synthesis. The TA-functionalized Agr (AgrTA) so obtained can be deposited onto titanium (Ti), stainless steel (SS), and silicon surfaces via direct adsorption and intermolecular oxidative cross-linking. The AgrTA-deposited SS surfaces show good stability in flowing electrolytes of varying pH. The AgrTA-deposited SS surfaces can also effectively reduce the adsorption of bovine serum albumin and the adhesion of Escherichia coli and 3T3 fibroblasts. In perhaps what is an ironic twist, t...

Purpose To evaluate the efficacy and long-term outcome of radical intracapsular microenucleation technique for the treatment of exclusively intraparotid facial nerve schwannoma (IFNS). Materials and methods From 1996 to 2015, IFNSs closely adherent to the facial nerve without intratemporal involvement were selected for this study. IFNSs were subdivided into an intracapsular microenucleation group and a resection with reconstruction group. Facial nerve function was assessed using the House-Brackmann Grading system. The study sample consisted of 28 patients who were followed up for 5.75 years (range, 1–15 years). Results Of the 28 patients, 18 IFNSs were from the main trunk. Radical intracapsular microenucleation was performed in 9 patients, resection with reconstruction in 7 patients, and only biopsy in 2 patients. Nine patients who received intracapsular microenucleation recovered to House-Brackmann Grade I (55.6%) or Grade II (44.4%), in comparison to the 7 patients from resection group (Grade III, 28.6%; Grade IV, 42.9%; Grade V, 28.6%). The other 10 IFNSs from the distal branches maintained favorable nerve function with either of the treatments. Tumor recurrence was not observed except for the two patients with only biopsy. Conclusion Radical intracapsular microenucleation with nerve preservation was a safe and reliable treatment for IFNS, especially for the IFNS from the main trunk.

Background Prefoldin (PFDN) subunits have recently been found to function importantly in various tumor types, while the role of PFDN subunit 1 (PFDN1) in gastric cancer (GC) remains largely unknown. Herein, we aimed to investigate the clinical significance, the biological role and the underlying mechanism of PFDN1 in GC development. Materials and Methods PFDN1 expression levels were measured in human GC specimens by quantitative real-time PCR (qRT-PCR), Western blot and immunohistochemistry. Furthermore, the effects of aberrant PFDN1 expression on GC cells behavior were assessed by wound-healing assay and transwell assay in vitro, and metastasis assay in nude mice, as well as Wnt/β-catenin signaling-induced epithelial–mesenchymal transition (EMT)-related markers by qRT-PCR and Western blot. Results PFDN1 levels were significantly upregulated in GC tissues compared with those in matched adjacent normal tissues. PFDN1 upregulation correlated strongly with clinical metastasis and unfavorable prognosis for GC patients. In vitro and in vivo studies revealed that PFDN1 facilitated GC cell migration, invasion and metastasis. Mechanically, PFDN1 modulated GC cell behavior by activating Wnt/β-catenin signaling-mediated EMT. Conclusion These results suggested a central role of PFDN1 in GC metastatic development via the Wnt/β-catenin pathway, thus providing a potential therapeutic target for patients with GC.

Disuse osteoporosis is common in prolonged therapeutic bed rest, space flight and immobilization due to limb fracture, which is related to reduction of mechanical stress on bone. Mechanical unloading can inhibit the differentiation of osteoblasts, but the detailed mechanism is still unclear. Runt-related transcription factor-2 (Runx2), is an important transcription factor, which plays a crucial role in disuse osteoporosis induced by unloading conditions. In this study, we found that Runx2-targeting mechano-sensitive miR-30 family members, miR-30b, miR-30c, miR-30d and miR-30e increased significantly, and were negatively correlated with the expression of Runx2 under unloading condition. Further studies found that the four miRNAs inhibited the expression of Runx2 and osteoblast differentiation under normal loading, and the knockdown of these miRNAs attenuated partly the inhibition of osteoblast differentiation induced by unloading condition in MC3T3-E1 cells. This study is the first to report miR-30 family members can regulate partly the dysfunction of osteoblasts under unloading condition, which is expected to be targets for the treatment of disuse osteoporosis.

Recently, microRNAs (miRNAs) have been reported to play crucial roles in immune responses and other biological processes, but the role of miR-181a in myasthenia gravis (MG) has been relatively less studied. We found that miR-181a was downregulated in the peripheral blood mononuclear cells (PBMCs) of MG patients and was associated with QMGs and anti-AChR Ab levels. In vitro experiments indicated that miR-181a was involved in the modulation of CD4+ T cell activation and plasticity and that miR-181a decreased the expression level of the Th1-related transcription factor T-bet and the Th17-related transcription factor RORγt. In the in vivo experiment, miR-181a treatment alleviated experimental autoimmune myasthenia gravis (EAMG) symptoms and affected both CD4+ T cell differentiation and the production of anti-AChR antibodies. Moreover, in this study, we also found that IL-2 was regulated by miR-181a and that its expression level showed a strong negative correlation with miR-181a levels in MG patients. To illustrate that the expression levels of both IL-2 and miR-181a were sensitive to immunomodulatory therapy treatment in MG, we found that IL-2 and miR-181a were correlated with clinical severity. These findings demonstrate that miR-181a can contribute to the pathogenesis of MG by regulating IL-2 expression. This article is protected by copyright. All rights reserved.

This paper presents a super efficiency network Data Envelopment Analysis (SE-NDEA) model for eleven cities in China. The model focuses on measuring the performance of public transit system by integrating multiple stakeholders involved in public transit system with the exogenous environment in where they operated. Thus, local authority, bus operators, passengers, uncontrollable environmental factors, and the externality of public transit are all taken into account in the measurement framework. They are interrelated inputs and outputs. The measurement framework can simultaneously capture each public transit system&rsquo, s production efficiency, service effectiveness, and operational effectiveness. Meanwhile, undesirable outputs, uncontrollable factors, and boundary-valued variables are considered. The paper evaluates the performance of public transit system of 11 Chinese cities from 2009 to 2016. The results reveal that the exogenous environment has a marked impact on the performance measurement of public transit system. Super cities tend to perform better than mega cities, and mega cities tend to perform better than large cities. Furthermore, service effectiveness has a significantly positive correlation with production efficiency, and transit rail tends to perform better than the conventional bus. These findings have an important implication for China&rsquo, s bus priority implement and more general managerial insights for public transit development.

Histone deacetylase 9 functions as an oncogene in a variety of cancers, but its role on non-small cell lung cancer (NSCLC) has not been reported. Melatonin was proven to possess anticancer actions, whereas its effect on NSCLC and underlying mechanisms remains poorly understood. In this study, 337 patients with complete clinicopathologic characteristics who underwent NSCLC surgery were recruited for the study. We found that NSCLC patients with high HDAC9 expression were correlated with worse overall survival and poor prognosis. HDAC9 knockdown significantly reduced NSCLC cell growth and induced apoptosis both in vivo and in vitro. Melatonin application also markedly inhibited cell proliferation, metastasis, and invasion and promoted apoptosis in NSCLC cells. Moreover, RNA-seq, real-time quantitative polymerase chain reaction, and western blot analyses showed that melatonin treatment decreased the HDAC9 level in NSCLC cells. A mechanistic study revealed that HDAC9 knockdown further enhanced the anticancer activities of melatonin treatment, whereas HDAC9 overexpression partially reversed the melatonin's anticancer effects. Additionally, the in vivo study found melatonin exerted anti-proliferative and pro-apoptotic effects on xenograft tumors which were also strengthened by HDAC9 knockdown. These results indicated that HDAC9 downregulation mediated the anti-NSCLC actions of melatonin, and targeting HDAC9 may be the novel therapeutic strategy for NSCLC.

The abrasion of hydraulic concrete structures caused by the washing action of flowing water is a common problem and cannot be solved by simply increasing the strength of the concrete. To ensure safe operation, increase in service life and reduction of maintenance costs of hydraulic concrete structures and the development of abrasion-resistant materials are required. In this work, polyurethane-modified epoxy resin was synthesized using the interpenetrating network technology (IPN). After many mixing experiments, the ratio of polyether amine to alicyclic amine in Component B was determined to be 29 : 14 and the ratio of Component A to Component B was 7 : 3. With these ratios, elastic epoxy achieved a tensile strength of more than 15 MPa and an elongation rate of more than 20%, thus balancing strength and toughness. The effects of the curing conditions, the ratio of Component A to Component B, and diluents and fillers on tensile strength and elongation of the elastic epoxy resin were analyzed. The results of the analysis indicated that the curing duration should be over 7 days, the optimal proportion of Component A to Component B should be 7 : 3, and the diluent of the elastic epoxy material should be the bifunctional butanedioldiglycidyl ether (622). The reliability of this material was determined by pull-out testing, adhesion, and tensile strength testing. The underwater steel ball test and ring test were adopted as the abrasion-resistance tests for the elastic epoxy resin material. The results showed that the abrasion-resistance performance of elastic epoxy coating improved hundreds of times over that of common concrete. Although the wearing strength was reduced with pressure, the elastic epoxy coating still retained excellent abrasion-resistance performance. At last, future application prospects of elastic epoxy improvement products are introduced and need further reach.

Pterostilbene (3,5-dimethoxy-4'-hydroxystilbene) is a polyphenolic compound primarily found in blueberries, grapes, and a tree wood, pterocarpus marsupium. Studies demonstrate that pterostilbene inhibits a variety of cancers, such as lung, breast, stomach, colon, etc. The anti-cancer activities are related to the regulation of several hallmarks of cancer. Moreover, pterostilbene exhibits much greater bioavailability and bioactivity than resveratrol which warrants further investigation in the anti-cancer functions and mechanisms. .【中文题目：紫檀芪抗肿瘤作用机制研究进展】 【中文摘要：紫檀芪（3,5-二甲氧基-4’-羟基二苯乙烯）是一种主要存在于蓝莓、葡萄和花榈木中的多酚类化合物。已有的研究发现紫檀芪具有抗肺癌、乳腺癌、胃癌、结肠癌等多种肿瘤的抗癌作用。其作用机制涉及调控影响多种肿瘤生物学特性。此外，紫檀芪具有比白藜芦醇更高的生物利用度和生物活性，其抗肿瘤作用和机制值得深入探讨和研究。 】 【中文关键词：紫檀芪；肿瘤；凋亡；增殖；侵袭】.

The structures and spectral properties of three ruthenium complexes with 8-hydroxyquinoline (Hhqn) and their derivatives 2-methyl-8-quinolinoline (H2mqn) and 2-chloro-8-quiolinoline (H2cqn) as ligands (QN = hqn, 2mqn, or 2cqn) were calculated with density functional theory (DFT) at the B3LYP level. The UV-Vis and IR spectra of the three [RuCl(QN)NO]−complexes were theoretically assigned via DFT calculations. The calculated spectra reasonably correspond to the experimentally measured spectra. Photoinduced NO release was confirmed through spin trapping of the electron paramagnetic resonance spectroscopy (EPR), and the dynamic process of the NO dissociation upon photoirradiation was monitored using time-resolved infrared (IR) spectroscopy. Moreover, the energy levels and related components of frontier orbitals were further analyzed to understand the electronic effects of the substituent groups at the 2nd position of the ligands on their photochemical reactivity. This study provides the basis for the design of NO donors with potential applications in photodynamic therapy.

With the popularization of mobile communication technology and Internet of things, wireless data transmission operation occupies an important position. Massive data generated by the Internet of things system is applied to the Internet of things system by wireless communication network and wireless resource management. Wireless network communication technology is the use of radio waves for data transmission, is a new type of communication information system, for the future development of communication system has established the direction. The wireless communication system is introduced into the middleware of the Internet of things system to improve the security and reliability of the Internet of things and ensure the timely and effective dissemination of information and data in the Internet of things system.

Surface coatings are extensively applied on biomedical devices to provide protection against biofouling and infections. However, most surface coatings prevent both bacteria and cells interactions with the biomaterials, limiting their uses as implants. Furthermore, damage to the surface such as scratches and abrasions can happen during transport and clinical usage, resulting in the loss of antibacterial property. In this work, we introduce an efficient method to fabricate stable anti-infective and self-healable multilayer coatings on stainless steel surface via a three-step procedue. Firstly, modified polyethyleneimine (PEI) and poly(acrylic acid) (PAA), both contain pendant furan groups, were deposited on the surface using Layer-by-Layer (LbL) self-assembly technique. Secondly, the polymer layers were cross-linked, via Diels-Alder cycloaddition, using a bismaleimide poly(ethylene glycol) linker, to enhance the stability of the coatings. Thirdly, the Diels-Alder adduct was utilised in the thiol-ene click reaction for post-modification of the coatings, which allowed for the grafting of antimicrobial poly(hexamethylene biguanide) (PHMB) and e-poly(lysine) (EPL). The resultant multilayer coatings not only exhibited rapid self-healing property, with complete scratch closure within 30 min, but also demonstrated effective antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). In addition, biofouling of bovine serum albumin was found to be inhibited on the coated surfaces. Furthermore, these coatings showed no toxicity effect towards seeded osteoblastic cells (MC3T3-E1) and evidence of anti-inflamatory activity when tested against macrophage cell line U-937. Our coating method thus represents an effective strategy for the anti-infective protection of biomedical-devices having direct contact with tissues.

The pathophysiologic significance of the CD16+ monocyte subset has been demonstrated by its expansion in various autoimmune disorders. To date, the characteristics and roles of monocyte subpopulations in patients with neuromyelitis optica (NMO) have been poorly defined. We measured the percentages of the monocyte subsets in the peripheral blood, the levels of IL-1β and TNF-α mRNA in monocyte subsets and the concentrations of IL-1β and TNF-α in plasma and CSF from NMO patients. Our results showed that nonclassical monocytes were up-regulated in NMO patients and significantly elevated IL-1β and TNF-α expression was detected in it. In addition the increased nonclassical monocytes could be selectively suppressed by GC in patients with NMO.

In this paper, the wheat straw (WS) was modified using phytic acid (PA) to improve adsorption capacity for selective removal of methylene blue dye (MB, cationic dye). The morphology, structure and surface state of the modofied wheat straw using phytic acid (PA-WS) were characterized using scanning electron microscopy (SEM), fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS), respectively. The effects of pH, MB concentration, different temperatures and contact time on adsorption experiments were investigated. The maximum adsorption quantity of PA-WS for MB was up to 205.4 mg g−1 at 25 °C. Equilibrium adsorption isotherm data indicated a good fit to the Langmuir isotherm model and the adsorption kinetic was well-fitted by the pseudo-second-order model and the Elovich model. Regeneration study revealed that PA-WS can be reused effectively. These results indicated that PA-WS was a promising adsorbent for the removal of cationic dyes.

Layer-by-layer (LBL) deposition of polyethylenimine-β-cyclodextrin (PEI-β-CD) and ferrocene-modified chitosan (Fc-CHT) via host–guest interaction chemistry was developed for the fabrication of low-fouling, antimicrobial, and biocorrosion inhibition multilayer coatings on stainless steel. An electrochemical method is proposed to monitor and determine the LBL deposition process. The resulting multilayer coatings exhibit good resistance to bacterial adhesion, including Pseudomonas sp. and Staphylococcus aureus, and microalgal attachment of Amphora coffeaeformis. Settlement of barnacle cyprids is also significantly reduced on the bilayer-coated substrates. As the number of assembled host–guest bilayers increases, the antifouling efficacy, antimicrobial efficiency, and antibiocorrosion performance also improve progressively. The stability and durability of the multilayer coatings were ascertained after a 30-day immersion treatment in seawater. Thus, the multilayer coatings deposited via LBL method are potentia...

An optical aptasensor was developed for ultrasensitive detection of ochratoxin A (OTA) based on hybridization chain reaction (HCR) amplification strategy and fluorescent perylene probe (PAPDI)/DNA composites. Dendritic DNA concatamers were synthesized by HCR strategy and modified on magnetic nanoparticles through aptamer as medium. A large amount of PAPDI probe aggregated under the induction of DNA concatamers and caused fluorescence quenching. In the presence of OTA, the PAPDI/DNA composites were released from magnetic nanoparticles due to the strong affinity between aptamer and OTA. In ethanol, PAPDI monomers disaggregated and produced strong fluorescence. The present method displays excellent sensitivity and selectivity towards OTA.

Locoregional flaps are widely used for reconstruction of small and medium defects in the oral cavity. The submandibular gland flap is a pedicled flap, which derives its blood supply from the facial artery, based on the submandibular gland. We describe the use of the flap in 20 patients who required oropharyngeal reconstruction with a pedicled submandibular gland flap after resection of a tumour between July 2012 and October 2014. Patients with squamous cell carcinoma were excluded. All flaps were pedicled on the facial vessels (inferiorly in 17 patients and superiorly in 3). The indications were: reconstruction of intraoral mucosal defects (n=13), filling the parapharyngeal dead space (n=6), and obliteration of the mastoid (n=1). All the flaps atrophied, but with no clinical effect. One patient developed partial loss of the flap, and one early leakage. There were no cases of xerostomia, and no signs of recurrence during the postoperative follow-up period of 3-26 months. The flap is useful, as it is simple and reliable for reconstruction of small to medium oropharyngeal defects in carefully selected cases, and gives good cosmetic and functional results.

Synergistic effect against UMUC3 bladder cancer cells was demonstrated via a "two-in-one" combination of doxorubicin (Dox) and peptide-modified cisplatin (Pt-ALy) loaded in positively charged mucoadhesive chitosan-polymethacrylic acid (CM) nanocapsules. The in vitro killing efficacy of the dual drug-loaded nanocapsules (CM-Dox-PtALy) against UMUC3 cells after 4h- and 72h-treatment is much higher (with 5-16 times lower IC50) than either Dox- or Pt-ALy-loaded nanocapsules, resulting in combination indexes of much less than 1 (i.e. obvious synergism) at fractions of affected cells ranging from 0.2 to 0.8. The dose reduction index of Pt-ALy for 72h-treatment is higher than for 4h-treatment, suggesting that Dox in CM-Dox-PtALy played a more significant role in the synergy in the former. The drug-loaded CM nanocapsules are readily taken in by the cells as shown by flow cytometry, confocal laser scanning microscopy and inductively coupled plasma mass spectrometry. Microscopy observations indicate that CM nanocapsules attach strongly on the luminal surface of the bladder with no obvious damage of the urothelium, supporting our objective of prolonging the dwell time of the drug-loaded nanocapsules for intravesical applications. Our study indicates that the mucoadhesive CM-Dox-PtALy nanocapsules have a high drug loading and a sustained release profile, and thus, are promising for synergistic intravesical chemotherapy of non-muscle-invasive bladder cancers.

Tannic acid can serve as an initiator anchor for surface functionalization. Parasin I is an antimicrobial peptide derived from histone. Multilayer coatings on stainless steel were prepared by alternative deposition of these two materials via the Michael addition/Schiff base reaction-enabled layer-by-layer (LBL) deposition technique. The as-prepared multilayer coating exhibits good resistance to Gram-negative bacteria (Pseudomonas sp. and E. coli), Gram-positive bacteria (S. aureus and S. epidermidis) and microalgae (Amphora coffeaeformis). The antifouling and antimicrobial efficacy increase with an increasing number of the assembled multilayers. The stability and durability of multilayer coatings were also ascertained by prolonged exposure to seawater. The LBL covalently deposited multilayer coatings are thus potentially useful as effective and environmental benign coatings to combat biofouling in marine and aqueous environments.

In this work, well-defined PEG-based fibrous hydrogels (FH's) were successfully prepared via electrospinning and in situ copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) reaction. Initially, the linear functional PEG derivatives with pendant alkynyl groups (PEGn(CCH))m and with azido moieties (PEGn(N3))m were synthesized via epoxide-amine chain-extension reaction between poly(ethylene glycol) diglycidyl ether (PEGDGE) and propargylamine/1-azido-3-aminopropane. Subsequently, the PEG-based FHs were fabricated from the blends of poly(ethylene oxide) (PEO) and the functional PEG derivatives via electrospinning and in situ CuAAC reaction using the encapsulated copper nanoparticles as the catalyst. The blends of PEO and the functional PEG derivatives were also utilized to prepare the microscopic hydrogels (MH's). The properties of the FH's and MH's were investigated by scanning electron microscopy (SEM) observation, swelling ratios, differential scanning calorimetry (DSC) and in vitro degradation. The copper nanoparticles-encapsulated FH's and MH's were further used to catalyze the CuAAC reaction in a small molecule model. The reusability of the FH's for the CuAAC reaction was also studied.

In-situ growth of a TiO2/g-C3N4 film with Z-scheme heterojunction structure on the hydrothermally treated titanium alloy via a calcination approach was firstly demonstrated in this work. Compared with the hydrothermally treated substrates, the as-prepared samples showed good hydrophilicity and osteoblast-like cell proliferation, evidencing their potential for improving the biocompatibility and osteogenesis of titanium alloy. Subsequently, more than 65% of E. coli was reduced on the surface of TiO2-g-C3N4 film under natural sunlight, indicating an enhanced antibacterial activity. The noticeably improvement of the antibacterial performance was ascertained mainly due to the presence of Z-scheme heterojunction between TiO2 and g-C3N4. Such structure could not only improve the separation and transfer of photogenerated carriers, but also increase the number of photogenerated electrons, thus enhancing the yielding of reactive oxygen species (ROS) to kill bacteria.

Three nitrosylruthenium complexes, [RuCl(qn)L(NO)] (qn = 8-hydroxyquinoline; L = l -Asp, l -Lys and picp), have been synthesized. The photodynamic reactions of the three complexes were analyzed with time resolved FTIR spectroscopy and the photoinduced release of NO was confirmed by EPR via spin trapping of the NO free radical. The binding constants of the complexes with calf thymus DNA and human serum albumin were quantitatively determined by fluorescence spectroscopy, with a stronger binding being found for the [RuCl(qn)(picp)(NO)] (picp = 2-(4-carboxylphenyl)-imidazolium[4,5-f][1,10] phenanthroline) complex compared to the other two complexes. Photoirradiation of the complexes mixed with HSA solution resulted in a blue-shift of the vibrational frequency of NO and an increased amount of released NO. The cell toxicity of the complexes was screened to understand the effects of the different ligands on the biological activity of the Ru complexes. The [RuCl(qn)(picp)(NO)] complex showed better activity against the HepG-2 cell, with an IC50 value of 24.9 µM without light and 13.8 µM upon photoirradiation. Moreover, a comparison of photoinduced DNA cleavage and photodynamic cellular toxicity suggests the important role of the NO free radical. This study provides a strategy for the design of NO-donors and the potential application of Ru-NO complexes in photodynamic therapy.