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Photonic materials that enable visual detection of chemicals have shown great potential for wide applications in chemical, environmental, biotechnological, and food industries, but until now, using hydrophilic photonic materials for tracing water-soluble chemicals remains a major challenge due to the strong water interference. Here, we demonstrate a two-step co-assembly and subsequent surface coating strategy to develop an ethanol-sensitive and anti-water interference photonic crystal film. By using citric acid as a co-assembly phase, high ethanol sensing is realized because of the strong intermolecular affinity. By controlling the thickness of the outer polyvinyl butyral layer, selective ethanol penetration but a water barrier is enabled. Notably, the composite photonic films are free-standing, highly flexible, and controllably structurally colored. We further present using the composite film to quantitatively trace ethanol/water mixtures and potentially track drunk driving as a colorimetric sensor. The heuristic two-step modification strategy proposed in this work not only overcomes the limitation of water interference for hydrophilic colorimetric sensors but also provides references to develop more new photonic materials with water resistance that need to be applied in water/humid environments.

Background Endoplasmic reticulum (ER) and mitochondrial dysfunction play fundamental roles in the pathogenesis of diabetic retinopathy (DR). The communication between the mitochondria and the ER is mediated by a functional subdomain referred to as the mitochondria-associated membrane (MAM). However, the mechanism underlying material exchange between the ER and mitochondria are poorly understood. This study aimed to explore the role of IP3R1-GRP75-VDAC1 axis in modulating Ca2+ homeostasis in RMECs. Methods In this study, we established high glucose (HG) and advanced glycosylation end products (AGEs)-induced human retinal vascular endothelial cells (RMECs) models in vitro, and streptozotocin (STZ)-induced DR model in vivo. CCK8 assay and Calcein-AM/PI double stain were used to detect cell viability.The ER-Tracker Red Kit and MitoTracker-Green are used to co-localize ER and mitochondria. Mitochondrial Ca2+ was detected using Rhod-2 AM. Co-immunoprecipitation (co-IP) was used to examine the interaction between IP3R1, GRP75 and VDAC1. MitoSOX™ Red Probe, mPTP Assay, and JC-1 Assay are used to measure mitochondrial function. Evans blue dye, retinal PAS staining, and TUNEL assay were used to assess retinal function. Results Our data demonstrated that there was increased ER-mitochondria coupling in the RMECs, which was accompanied by elevated mitochondrial calcium ions (Ca2+) and mitochondrial dysfunction (mitochondrial membrane potential, ΔΨm; and mitochondrial ROS) under HG or AGEs transferred ER Ca2+ into the mitochondria. Elevated mitochondrial Ca2+ concentrations led to an increase in mitochondrial ROS and a decline in mitochondrial membrane potential. These events resulted in mitochondrial dysfunction and elevation of mitochondrial permeability, which induced cytoplasmic Cyt c/Caspase-3-mediated cell apoptosis. The above phenomenon was reversed by BAPTA-AM (an intracellular calcium chelator) and tunicamycin (TUN), a common ERS inducer. In addition, 4-PBA, (an ERS inhibitor), was shown to reverse retinal dysfunction in STZ-induced DR rats. Conclusions Our findings demonstrated that DR fuels the formation of ER-mitochondria coupling via the IP3R1-GRP75-VDAC1 axis, which facilitates transport of Ca2+ from the ER to the mitochondria, eventually leading to mitochondrial dysfunction and apoptosis of endothelial cells. Our results demonstrated that inhibition of ER-mitochondrial coupling, including inhibition of GRP75 or Ca2+ overload, may be a potential therapeutic target in DR.

Biomimetic optical cellulose nanocrystal (CNC) materials have shown great potential for application in colorimetric sensing, anticounterfeiting, and decorative coatings because of simple recognitio...

Background: Tuberculosis (TB) represents a bacterial infection affecting many individuals each year and potentially leading to death. Overexpression of transforming growth factor (TGF)-β1 has a major immunomodulatory function in human tuberculosisThis work aimed to develop nanoliposomes to facilitate the delivery of antituberculous products to THP-1-derived human macrophages as Mycobacterium host cells, and to evaluate drug efficiencies as well as the effects of a TGF-β1-specific short interfering RNA (siRNA) delivery system employing nanoliposomes.Methods: siTGF-β1 nanoliposomes loaded with the anti-TB drugs HRZ (isoniazid, rifampicin and pyrazinamide) were prepared, and characterized in vitro, determining the size, zeta potential, morphology, drug encapsulation efficiency (EE), cytotoxicity, and gene silencing efficiency of TGF-β1 siRNA.Results: HRZ/siTGF-β1 nanoliposomes appeared as smooth spheres showing size and positive zeta potential of 168.135±0.5444 nm and +4.03±1.32 mV, respectively. Drug EEs were 90%, 88%, and 37% for INH, RIF, and PZA, respectively. Meanwhile, the nanoliposomes were weakly cytotoxic towards human macrophages as assessed by the MTT assay. Nanoliposomal siTGF-β1 could significantly downregulate TGF-β1 in THP-1-derived human macrophages in vitro.Conclusion: These findings suggested that HRZ-loaded nanoliposomes with siTGF-β1 have the potential for improving spinal tuberculosis chemotherapy via nano-encapsulation of anti-TB drugs.

Developing probes with good biocompatibility and realizing intracellular detection in living cells are of great significance for biomedicine and life sciences, but remain a challenge presently. In this paper, we describe a rapid and highly selective biosensor for Fe

Cellulose nanocrystal (CNC) is an interesting polysaccharide nanomaterial that can self-assemble into a chiral nematic liquid crystalline structure in aqueous solution, producing brightly structural color upon selectively reflection of visible light. However, till now, only iridescent structural colors can be created by such colloidal array, making it impossible to be used as colorimetric sensors. Here, inspired by longhorn beetle having short-range ordered but long-range disordered microstructures, it is demonstrated to develop low-/non-angle-dependent structural-color CNC composite films through interference against the long-range orders as a result of introducing positively charged poly (dimethyl diallyl ammonium chloride) (PDDA). By exploring balanced ordered/disordered structures, vivid angle-independent structural colors are realized, enabling accurate cognition for environmental signals, which is crucial to promising applications in sensing, anti-counterfeit, and decoration technology.

Developing probes with good biocompatibility and realizing intracellular detection in living cells are of great significance for biomedicine and life sciences, but remain a challenge presently. In this paper, we describe a rapid and highly selective biosensor for Fe3+ detection in living cells based on the Maillard reaction fluorescent products (MRFPs) of glutathione and ascorbic acid as a probe. Experiments show that the MRFPs are non-cytotoxic and possess excellent biocompatibility. Moreover, the MRFPs show a rapid response and good selectivity towards Fe3+ over other metal ions under physiological pH conditions in vitro. The introduction of Fe3+ can quench the fluorescence of MRFPs, and the fluorescence intensity of system decreases linearly with the increasing concentration of Fe3+ in the range of 0.05–50 μM with the detection limit of 4.6 nM at a signal-to-noise ratio of 3. Moreover, the recognition mechanism has been discussed, which is attributed to the charge transfer from excited-state MRFPs molecules to metal ions. In addition, the MRFPs have been successfully demonstrated to be a good imaging probe for Fe3+ sensing in living cells. This study shows that the biocompatible MRFPs might hold great potential for applications in bioimaging, diagnosis, and therapy of intracellular diseases.

Bladder dysfunction is associated with fibrosis‑-mediated aging, but the corresponding mechanism remains to be elucidated. Activation of the NACHT, LRR and PYD domains‑containing protein 3 (NLRP3) inflammasome is related to chronic diseases associated with aging, including organ fibrosis. The present study aimed to explore the role of NLRP3/interleukin 1β in aging‑associated bladder dysfunction. Female Sprague‑Dawley rats were divided into the following two groups (n=10 rats/group): 2‑month‑old group (young group) and 24‑month‑old group (old group). Urodynamics were performed to assess the bladder function of the rats. The histological alterations were identified using Masson's trichrome staining. The protein expression of the NLRP3 inflammasome and NAD‑dependent protein deacetylase sirtuin‑3, mitochondrial (SIRT3) were detected by western blot analysis, and immunohistochemistry was used to examine a senescence marker (p21) and the NLRP3 inflammasome in the bladder. The localization of the key molecule Caspase1 was determined using immunofluorescence. The voiding time was longer in the old group compared with the young group. The expression levels of SIRT3 were reduced in the bladders of the old group, while those of the NLRP3 inflammasome and the senescence marker were significantly higher in the bladders of the old group compared with the young group. Increased collagen deposition leads to chronic bladder fibrosis with increased NLRP3. In the histological examination, the bladders of the old group displayed increased collagen deposition, urothelial thinning and detrusor shrinkage compared with the young group. Tissue fibrosis and urothelial alterations are the principal causes of bladder dysfunction during aging. Downregulated SIRT3 and upregulated expression of the NLRP3 inflammasome are involved in the degradation of aging bladders. Inflamm‑aging is a novel mechanism underlying bladder dysfunction.

This research proposes a reliability simulation method combining the finite element simulation technology and stress-strength model to predict the structural reliability of girth welds with the following steps. Firstly, a group of finite element simulations of the girth welds are carried out considering uncertainties of elastic moduli in the weld and core barrel materials. Then the maximum von-Mises stresses over the welds are extracted from those simulations to generate the stress distribution. Finally through a stress-strength model, the structural reliability of the girth weld is calculated by assuming its yield strength following a Normal distribution. In addition, via the proposed method, influences factors such as temperature, pressure and the uncertainty level among the elastic modulus on the weld reliability are discussed in detail.

Spinal cord injury (SCI) is a severe traumatic lesion of central nervous system (CNS) with only a limited number of restorative therapeutic options. Diosgenin glucoside (DG), a major bioactive ingredient of Trillium tschonoskii Max., possesses neuroprotective effects through its antioxidant and anti-apoptotic functions. In this study, we investigated the therapeutic benefit and underlying mechanisms of DG treatment in SCI. We found that in Sprague-Dawley rats with traumatic SCI, the expressions of autophagy marker Light Chain 3 (LC3) and Beclin1 were decreased with concomitant accumulation of autophagy substrate protein p62 and ubiquitinated proteins, indicating an impaired autophagic activity. DG treatment, however, significantly attenuated p62 expression and upregulated the Rheb/mTOR signaling pathway (evidenced as Ras homolog enriched in brain) due to the downregulation of miR-155-3p. We also observed significantly less tissue injury and edema in the DG-treated group, leading to appreciable functional recovery compared to that of the control group. Overall, the observed neuroprotection afforded by DG treatment warrants further investigation on its therapeutic potential in SCI.

The full opening of the northern shipping line puts forward a great challenge for the safety of polar ships, the presence of floating ice increases the possibility of collision between ship and sea ice. However, due to the complex mechanical properties of sea ice, a reasonable description of its material constitutive relation is the main factor affecting the accusation of calculation and analysis. In this paper, a constitutive model of ice material considering the effect of temperature is presented, a user-defined subroutine is developed and embedded into the finite element software LS-DYNA. Based on this, the damage and deformation characteristics of the ship structure and ice is studied, and effects of collision scenario parameters are discussed. The results of this paper can provide reference for the design and manufacture of polar ships.

Background Posterior instrumentation after deformity correction is an important method for reconstruction of spinal stability in the management of lumbar tuberculosis (TB). However, the commonly used methods include both long- and short-segment fixation of normal motor units. There has been no report regarding affected-vertebrae fixation of lumbar TB. Methods Data from 135 patients with lumbar TB who underwent posterior instrumentation and either affected-vertebrae fixation or short-segment fixation using a combined posterior and anterior approach were retrospectively reviewed. Among these patients, 71 cases were treated with affected-vertebrae fixation, and 64 cases were treated with short-segment fixation. Debridement, bone grafting, deformity correction, and decompression were performed within all affected segments. Operative times, intra-operative blood loss, TB cure rates, bone graft fusion rates, degree of deformity correction, neurological function, pain recovery, and complications were analyzed. Results Comparing affected-vertebrae fixation vs. short-segment fixation groups, respectively, the number of the affected segments was 107 vs. 98; average number of affected segments was 1.51 vs. 1.53; total number of fixed segments was 107 vs. 226; average number of fixed segments was 1.51 vs. 3.53; average blood loss was 726.2 ml vs. 948.5 ml; average operative time was 210.4 min vs. 270.3 min; and average hospitalization costs were 29,000 RMB vs. 42,000 RMB (all p values 0.05). Conclusion Under strict surgical indications, posterior instrumentation on affected-vertebrae is a safe, effective, and feasible fixation method in the treatment of lumber TB.

As the failure of a hydraulic pump is always instantaneous, the failure data are difficult to obtain. High-efficiency fault diagnosis under small-sample conditions for hydraulic pumps is urgently required in engineering applications. A fault diagnosis approach based on wavelet packet transform (WPT), singular value decomposition (SVD), and support vector machine (SVM) is proposed in this study. First, the nonlinear, non-stationary vibration signal of the hydraulic pump is decomposed into components by WPT. Second, singular value vectors are acquired as feature vectors by applying SVD to the components. Third, the health states of the hydraulic pumps are determined and classified with a SVM classifier. Furthermore, the SVM and Elman neural network classifiers are compared in terms of fault classification to demonstrate the superiority of SVM in dealing with small-sample problems. The results of the plunger pump rig test show that the proposed method can diagnose the faults of the hydraulic pump accurately even when the number of samples is small.

A rotary actuator that employs hydraulic oil as the power source has a direct rotary structure. It is an important structure and has been widely utilized in aircrafts and ships because of its advantages, including large torque/quality ratio, simple compact structure, and fast dynamic response. Huge damage may be caused when a rotary actuator breaks down during operation. However, only a few studies have focused on fault detection and performance assessment for rotary actuators. In this study, a method that detects the fault in and assesses the performance of the rotary actuator based on residual analysis is proposed. The data in normal state are utilized to build an observer with two radial basis function (RBF) neural networks. One RBF neural network is employed to estimate the expected output required to generate the residuals. The self-adaptive thresholds are obtained through the other RBF neural network. The residual is then inputted into the self-organizing mapping neural network trained by the residual values in normal state to normalize the performance of the rotary actuator into confidences values between 0 and 1. Finally, the detection and assessment of two typical faults of the rotary actuator are simulated. Results verify the efficiency of the proposed method.

During the expansion of aging population, the study correlated with brain aging is one of the important research topics. Developing novel and effective strategies for delaying brain aging is highly desired. Brain aging is characteristics of impaired cognitive capacity due to dysfunctional autophagy regulated by Rheb-mTOR signal pathway in hippocampal tissues. In the present study, we have established a rat model with brain aging through subcutaneous injection of D-galactose (D-gal). Upon the intervention of Trillium tschonoskii Maxim (TTM) saponin, one of bioactive components from local natural herbs in China, the learning and memory capacity of D-gal-induced aging rats was evaluated through Morris water maze test, and the regulation of Rheb-mTOR signal pathway and functional status of autophagy in hippocampal tissues of D-gal-induced aging rats was explored by Western blot. TTM saponin revealed an obvious function to improve learning and memory capacity of D-gal-induced aging rats through up-regulating Rheb and down-regulating mTOR, thereby rescuing dysfunctional autophagy to execute anti-aging role. Meanwhile, this study confirmed the function of TTM saponin for preventing and treating brain aging, and provided a reference for the development and utilization of natural products in health promotion and aging-associated disease treatment.

Aims Open surgery is the most commonly used methodological approach for generating a partial bladder outlet obstruction (pBOO) animal model. Surgical suturing closing a part of the urethral meatus induces comparable pathophysiological changes in bladder and renal functions, but the optimum degree of obstruction that closely mimics the clinical pathology of pBOO has not been elucidated. We investigated the optimum obstruction level by performing a comprehensive time-dependent analysis of the stability and reliability of this novel animal model. Methods Six- to eight-week-old female BALB/c mice were divided into three groups according to the degree of urethral meatus stricture (UMS). Non-operated mice served as controls, and a pBOO model generated using the traditional method served as a positive control. A cystometric evaluation and long-term studies were performed to evaluate the validity and reliability of this novel animal model. An additional 35 mice were used to investigate the protein expression levels and histopathological features 24 h and 14 days postoperatively, respectively. Results The characteristic cystometry features in the UMS group revealed increased changes in pressure-related parameters compared with the control. The 1/3 UMS model is an optional pBOO animal model because the cystometric evaluation and histopathological studies revealed a striking resemblance between the 1/3 UMS model and the model generated using the traditional open-surgery method. Conclusions The minimally invasive UMS model required less time and produced minimal alterations in pathophysiologically relevant processes compared with the traditional surgery model. Suturing to cause UMS produced effective and repeatable patterns in bladder function investigations in mice.

Debridement, spinal canal decompression, deformity correction, bone graft fusion and internal fixation are commonly used in the surgical treatment of spinal tuberculosis. A complete surgical plan for patients with spinal tuberculosis may include all or some of these five surgical procedures that involve both removing tuberculous lesions and re-establishing spinal stability and function. All five procedures can be carried out via an anterior or posterior approach or a combination of these two approaches. A combined posterior-anterior approach is becoming a preferred choice for treating spinal tuberculosis. However, this procedure requires two incisions and two rounds of surgeries, which the associated extensive surgical trauma. Thus, a simple anterior or posterior approach may be preferable. Each of these approaches has its own advantages and disadvantages that must be considered during the clinician's evaluation. Selection of the most appropriate of these three approaches is vital to achieving cure of spinal tuberculosis. Spinal surgeons should comprehensively consider each patient's characteristics, the manifestations of their lesions and how familiar the surgeon is with the required surgical procedure(s). The primary consideration should be the potential outcome: the effectiveness of debridement is the key determinant of the surgical outcome.

According to the characteristics of domain knowledge,a method for the determination of domain sememe is given,and a rule for the description of the domain semantic item is also given.Then,the method and the rule are applied to the failure domain.The model of semantic force is given in the process of semantic retrieval ,and the method for the calculation of semantic force is given.The method for the generation of the theme of failure mode is given.A retrieval method for failure mode based on semantic is given,and there is an example to prove its effectiveness.

Due to the importance of the Airborne Equipment Software (AES), much more attentions have been drawn into here. Building a unified, standardized and effective management AES defect knowledge base with these data is a definitely valuable work. In this paper a framework of software quality integrate prediction has been established, which is highly essential to make accurate evaluations on the quality, predictions on the defects, identifications on the fault-prone modules. A framework on how to build an AES knowledge base is proposed, a combination mechanism is proposed by involving machine learning technology and production system, in which, in order to provide the instructions for defect prediction and quality assessment of AES.

As availability of HFS is a basic indicator to measure the degree of usability, optimal maintenance strategy with maximum availability and cost constraints can provide a better platform for HFS scheduling. So this paper proposes a Semi-Markov Process (SMP) based availability model here focused on general maintenance strategy with machines life time distribution and maintenance time distribution. Then the maintainability parameters optimization method with total cost constrains is achieved based on the availability model. Furthermore, the proposed optimization method is applied to a two-stage HFS and showed to be effective.

Increasing evidence has suggested that high expression level of cyclooxygenase-2 (Cox-2) is associated with the malignancies of non-small cell lung cancer (NSCLC), leading to a rationale of applying Cox-2 inhibitors as adjuvant therapy in the treatment of NSCLC. However, the addition of celecoxib, a selective Cox-2 inhibitor, to chemotherapy in clinical trials failed to benefit the survival of NSCLC patients, which urges the investigation to re-evaluate this strategy for NSCLC treatment. In this study, we observed that celecoxib treatment at clinically relevant concentrations induced epithelial-mesenchymal transition (EMT) in NSCLC cells regardless of Cox-2 status, which, however, was not recapitulated using another Cox-2 inhibitor, etodolac. Celecoxib-stimulated EMT in turn promoted cell invasion and rendered cells resistant to chemotherapy. Further mechanistic investigation by disrupting the integrity of signaling pathways using specific inhibitors or RNA interference revealed that celecoxib-induced EMT in NSCLC cells is indispensable of transforming growth factor-β1/Smad signaling. Instead, the activated MEK/ERK/SNAIL1 signaling largely accounted for celecoxib-induced EMT. Taken together, our study reveals the diverse impacts of Cox-2 inhibitors on EMT in NSCLC cells independent of Cox-2 inhibition, where celecoxib treatment leads to metastasis and chemoresistance via EMT induction. These findings reveal the increased risks of cancer metastasis and chemoresistance by applying Cox-2 inhibitors, celecoxib in particular, in clinical trials of NSCLC treatment and urge intensive preclinical assessment before proceeding to clinical application.

This paper presents detailed technique and steps of data mining in sluice safety monitoring according to the monitoring data’s features. The tasks and objectives of data mining are defined and converted into the knowledge which can be realized by certain algorithm. The methods of data preprocessing is also discussed to eliminate or reduce redundant, noise, incomplete and inconsistent data. The examples of data preprocessing and data mining show how to apply the data mining technology in the sluice safety monitoring filed, which results indicate that the method presented in this paper is effective and can be used in other projects.

The out-of-plane quasi-static compressive behavior of four types of corrugated cores (V-type, U-type, X-type and Y-type core) has been investigated by experiment and FE simulations. By transient dynamic finite element analysis code MSC.Dytran numerical simulations were performed for calculating crushing forces, deformation mode and energy absorption. The FE simulations predict the crush behavior of cores with reasonable accuracy and provide the whole progressive buckling process and deformation modes. Experiment and simulation indicate that the U-type core, V-type core and X-type core structures show excellent crushing resistance performance and energy absorption characteristic. The crush performance of the Y-type core structures is relatively poor because of bending mode.

Through the three-point bending test on the specimens of steel fiber reinforced high strength concrete (SFHSC) and plain high strength concrete (HSC) with the size of 100 mm×100 mm×515 mm, the effects of influencing factors including the fiber volume fraction (ρf) and relative notch depth (a/W) upon the fracture energy and the work of applied force (gravity and external force) were studied. The results show that the effect of ρf upon the fracture energy is more obvious; the variation tendencies for the increment ratio of the fracture energy and that of the work of applied force are different under different factors; the fracture energy is dependent on the work of external force. Based on the test results, the formula was established for calculating the fracture energy.

Ning-Kui Niu,1–3 Juan-Juan Yin,3 Yin-Xue Yang,4 Zi-Li Wang,1 Zhi-Wei Zhou,3 Zhi-Xu He,5 Xiao-Wu Chen,6 Xueji Zhang,7 Wei Duan,8 Tianxin Yang,9 Shu-Feng Zhou3 1Department of Orthopedics, General Hospital of Tianjin Medical University, Tianjin, 2Department of Spinal Surgery, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China; 3Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA; 4Department of Colorectal Surgery, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 5Guizhou Provincial Key Laboratory for Regenerative Medicine, Stem Cell and Tissue Engineering Research Center and Sino-US Joint Laboratory for Medical Sciences, Guizhou Medical University, Guiyang, Guizhou, 6Department of General Surgery, The First People’s Hospital of Shunde Affiliated to Southern Medical University, Shunde, Foshan, Guangdong, 7Research Center for Bioengineering and Sensing Technology, University of Science and Technology Beijing, Beijing, People’s Republic of China; 8School of Medicine, Deakin University, Waurn Ponds, VIC, Australia; 9Department of Internal Medicine, University of Utah and Salt Lake Veterans Affairs Medical Center, Salt Lake City, UT, USA Abstract: Tuberculosis (TB) is still a major public health issue in developing countries, and its chemotherapy is compromised by poor drug compliance and severe side effects. This study aimed to synthesize and characterize new multimodal PEGylated liposomes encapsulated with clinically commonly used anti-TB drugs with linkage to small interfering RNA (siRNA) against transforming growth factor-β1 (TGF-β1). The novel NP-siRNA liposomes could target THP-1-derived human macrophages that were the host cells of mycobacterium infection. The biological effects of the NP-siRNA liposomes were evaluated on cell cycle distribution, apoptosis, autophagy, and the gene silencing efficiency of TGF-β1 siRNA in human macrophages. We also explored the proteomic responses to the newly synthesized NP-siRNA liposomes using the stable isotope labeling with amino acids in cell culture approach. The results showed that the multifunctional PEGylated liposomes were successfully synthesized and chemically characterized with a mean size of 265.1 nm. The novel NP-siRNA liposomes functionalized with the anti-TB drugs and TGF-β1 siRNA were endocytosed efficiently by human macrophages as visualized by transmission electron microscopy and scanning electron microscopy. Furthermore, the liposomes showed a low cytotoxicity toward human macrophages. There was no significant effect on cell cycle distribution and apoptosis in THP-1-derived macrophages after drug exposure at concentrations ranging from 2.5 to 62.5 µg/mL. Notably, there was a 6.4-fold increase in the autophagy of human macrophages when treated with the NP-siRNA liposomes at 62.5 µg/mL. In addition, the TGF-β1 and nuclear factor-κB expression levels were downregulated by the NP-siRNA liposomes in THP-1-derived macrophages. The Ingenuity Pathway Analysis data showed that there were over 40 signaling pathways involved in the proteomic responses to NP-siRNA liposome exposure in human macrophages, with 160 proteins mapped. The top five canonical signaling pathways were eukaryotic initiation factor 2 signaling, actin cytoskeleton signaling, remodeling of epithelial adherens junctions, epithelial adherens junction signaling, and Rho GDP-dissociation inhibitor signaling pathways. Collectively, the novel synthetic targeting liposomes represent a promising delivery system for anti-TB drugs to human macrophages with good selectivity and minimal cytotoxicity. Keywords: tuberculosis, cytokine, liposome, apoptosis, autophagy, cell cycle, proteomics, SILAC, NF-κB, interleukin

Among antioxidant enzymes, catalases protect microorganisms by degrading hydrogen peroxide under oxidative stress. In this study, the activities of at least four Vibrio parahaemolyticus catalases (Kat1 to Kat4) were differentially detected during different growth stages and under various stress conditions using zymographic analysis. Our results showed that only Kat2 is stable at 55 °C. Kat1 and Kat2 respond to hydrogen peroxide during the early stationary and exponential growth phases, respectively and the response decreases upon entering the stationary phase. Kat3 and Kat4 are bifunctional, exhibiting both catalase and peroxidase activities and are only expressed during the stationary phase, under starvation or under stress at pH 5.5. Our study also shows that expression of Kat3 and Kat4 depends on RpoS. We confirm that both monofunctional and bifunctional catalases are expressed and function differentially under various stresses to contribute total catalase activities for the survival of V. parahaemolyticus. A comparative genomic study among Vibrio species revealed that only V. parahaemolyticus contains two copies of genes that encode monofunctional and bifunctional catalases. We propose that both types of catalases, whether evolved or acquired horizontally through long-term evolution, may play crucial protective roles in V. parahaemolyticus in response to environmental fluctuations.

We study the normal-mode splitting when an oscillator is placed in a two-dimensional photonic crystal microcavity embedded with an impedance-matched or an impedance-mismatched zero-index medium (ZIM). Because of the (nearly) uniform localized fields in the ZIM, the normal-mode splitting remains (almost) invariant no matter where the oscillator is. When a split ring resonator is coupled to a transmission-line- based effective ZIM at various locations, nearly position-independent mode splitting is observed.

To assess the different causes of thoracic ossification of the ligamentum flavum (TOLF).From July 1989 to November 2005, 142 cases were diagnosed the TOLF, in which 121 were operated. The lesions were classified into three types on the basis of the clinical result: (1) In such primary group (Group 1, 90 cases), without incorporation disease and Ca, P and AKP was all normal; (2) In systemic ossified TOLF group (Group 2, 30 cases), 6 cases ankylosing spondylitis, 3 cases DISH, 10 cases fluorosis, 11 cases OPLL; (3) In local spine disease group (Group 3, 22 cases), 5 cases fracture in spine, 4 cases spine TB, 13 cases posterior marginal intraosseous cartilaginous node. Such clinical feature was analysed, moreover surveyed the thoracic kyphosis angle, upper thoracic kyphosis angle, lower thoracic kyphosis angle and the vertebra body wedge change. The effect was assessed using Epstein Scale.(1) In Group 1, the mainly type was connected type (67/90, 74%). The ossified ligamentum flavum was mainly located at the lower thoracic and thoracic-lumber levels. The local type was less. In Group 2, the mainly type was connected type (21/30, 70%). The local type was none. The lesions figure was the most. In Group 3, the local type was the most (18/22, 82%). (2) In Group 1, the ossified ligamentum flavum was mainly located at the upper and lower thoracic levels (225/486, 47%). In Group 2, mainly located at the whole thoracic, some include cervix and lumber. In Group 3, mainly location was related with the location of primary disease. (3) In group 1, the curve was normal in 81% (73/90) of cases. In Group 2, the curve was abnormal in 87% (26/30) of cases. In Group 3, the curve was normal in the 82% (18/22) of cases.The TOLF relates with systemic ossify disease, the change of load on the spine, aging and so on. It should be classified according to its causes.

To investigate the correlation of pathology, bone morphogentic protein (BMP) expression, CT value with the ossification of thoracic ligamentum flavum (TOLF) to afford the evidence to choose appropriate treatment methods.Twenty-three patients aged 35 - 65 years old had TOLF in my hospital as case. Their courses of disease were 2 months to 9 years. The values of blood calcium, blood phosphorus and AKP in them were normal. The 5 peoples aged 21 - 35 years old who presented fracture of thoracic but not the ligamentum flavum ossification were selected as control. We excluded those who have DISH, ankylosing spondylitis, fluorosis and other disease related with TOLF. The lesion locus were scanned and mensurated by CT. The pathology characteristics were classified into immature ossification and mature ossification by general observation, histology examination. BMP were measured by the immunohistochemical (IHC) staining techniques.The CT value was significantly higher in the case group (547.2 +/- 131.4) than controlled group (137.7 +/- 10.6) (t = 6.922, P = 0.000). Further, the CT value in the mature ossification (702.9 +/- 17.7) was significantly higher than the immature (480.5 +/- 180.2) (t = 5.623, P = 0.000). In addition, BMP both expressed negative in the mature ossification and the controlled group, but positive in the immature ossification. BMP expression was significantly different between the immature ossification and the mature (chi2 = 70.000, P = 0.000).The CT values, pathological types and BMP expression results are similar to evaluate the ossification degrees of ligamentum flavum, and then could be indirectly judged the maturation degrees of TOLF by CT to confirm the treatment methods before operation.

Ning-Kui Niu,1–3 Zi-Li Wang,1 Shu-Ting Pan,2,4 Hui-Qiang Ding,1 Giang HT Au,2 Zhi-Xu He,5 Zhi-Wei Zhou,2,5 Guozhi Xiao,6 Yin-Xue Yang,7 Xueji Zhang,8 Tianxin Yang,9 Xiao-Wu Chen,10Jia-Xuan Qiu,4 Shu-Feng Zhou2 1Department of Spinal Surgery, General Hospital of Ningxia Medical University, Yinchuan, People’s Republic of China; 2Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA; 3Department of Orthopedics, General Hospital of Tianjin Medical University, Tianjin, 4Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 5Guizhou Provincial Key Laboratory for Regenerative Medicine, Stem Cell and Tissue Engineering Research Center and Sino-US Joint Laboratory for Medical Sciences, Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 6Department of Biochemistry, Medical Center, Rush University, Chicago, IL, USA; 7Department of Colorectal Surgery, General Hospital of Ningxia Medical University, Yinchuan, 8Research Center for Bioengineering and Sensing Technology, University of Science and Technology Beijing, Beijing, People’s Republic of China; 9Department of Internal Medicine, University of Utah and Salt Lake Veterans Affairs Medical Center, Salt Lake City, UT, USA; 10Department of General Surgery, The First People’s Hospital of Shunde affiliated to Southern Medical University, Foshan, Guangdong, People’s Republic of China Abstract: Osteosarcoma (OS) is the most common malignant bone tumor occurring mostly in children and adolescents between 10 and 20 years of age with poor response to current therapeutics. Alisertib (ALS, MLN8237) is a selective Aurora kinase A inhibitor that displays anticancer effects on several types of cancer. However, the role of ALS in the treatment of OS remains unknown. This study aimed to investigate the effects of ALS on the cell growth, apoptosis, autophagy, and epithelial to mesenchymal transition (EMT) and the underlying mechanisms in two human OS cell lines U-2 OS and MG-63. The results showed that ALS had potent growth inhibitory, pro-apoptotic, pro-autophagic, and EMT inhibitory effects on U-2 OS and MG-63 cells. ALS remarkably induced G2/M arrest and down-regulated the expression levels of cyclin-dependent kinases 1 and 2 and cyclin B1 in both U-2 OS and MG-63 cells. ALS markedly induced mitochondria-mediated apoptosis with a significant increase in the expression of key pro-apoptotic proteins and a decrease in main anti-apoptotic proteins. Furthermore, ALS promoted autophagic cell death via the inhibition of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) and p38 mitogen-activated protein kinase (p38 MAPK) signaling pathways, and activation of 5'-AMP-dependent kinase (AMPK) signaling pathway. Inducers or inhibitors of apoptosis or autophagy simultaneously altered ALS-induced apoptotic and autophagic death in both U-2 OS and MG-63 cells, suggesting a crosstalk between these two primary modes of programmed cell death. Moreover, ALS suppressed EMT-like phenotypes with a marked increase in the expression of E-cadherin but a decrease in N-cadherin in U-2 OS and MG-63 cells. ALS treatment also induced reactive oxygen species (ROS) generation but inhibited the expression levels of sirtuin 1 and nuclear factor-erythroid-2-related factor 2 (Nrf2) in both cell lines. Taken together, these findings show that ALS promotes apoptosis and autophagy but inhibits EMT via PI3K/Akt/mTOR, p38 MAPK, and AMPK signaling pathways with involvement of ROS- and sirtuin 1-associated pathways in U-2 OS and MG-63 cells. ALS is a promising anticancer agent in OS treatment and further studies are needed to confirm its efficacy and safety in OS chemotherapy. Keywords: ALS, autophagy, apoptosis, osteosarcoma, PI3K/Akt/mTOR pathway, EMT