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Ascending aortic perivascular adipose tissue (AA-PVAT) mainly comprises brown adipose tissue (BAT), originates from neural crest cells that derive from ectoderm, and plays important role in angiotensin II-induced vascular inflammation and remodeling in mice. However, the characterization and function of human AA-PVAT remains highly unclear.Patients with coronary artery disease (CAD) (n = 20) and aortic valve disease (AVD) (n = 23) who underwent cardiac surgery consented to take part in transcriptome and histological studies. Paired samples of AA-PVAT, epicardial adipose tissue (EAT), and subcutaneous adipose tissue (SAT) were obtained. RNA sequencing, histological analysis, quantitative reverse transcription polymerase chain reaction and western blot studies were performed on those samples.Human AA-PVAT exhibited smaller adipocyte morphology and high expression of brown adipocyte marker. Transcriptome analysis revealed that AA-PVAT showed unique transcriptome characteristics compared with EAT and SAT. While comparing CAD and AVD patients, AA-PVAT exhibited a decreasing brown phenotype and higher inflammatory response in AVD patients. Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analysis suggested that the differentially expressed genes in AA-PVAT between CAD and AVD patients were involved mainly in the processes of inflammation and metabolism regulation.Human AA-PVAT is a BAT-like adipose tissue with unique transcriptome characteristics, and exhibits a weakened brown phenotype and an enhanced inflammation response in AVD patients.

The mercury constitutive model predicting the strain and stress in the target vessel plays a central role in improving the lifetime prediction and future target designs of the mercury targets at the Spallation Neutron Source (SNS). We leverage the experiment strain data collected over multiple years to improve the mercury constitutive model through a combination of large-scale simulations of the target behavior and the use of machine learning tools for parameter estimation. We present two interdisciplinary approaches for surrogate-based model calibration of expensive simulations using evolutionary neural networks and sparse polynomial expansions. The experiments and results of the two methods show a very good agreement for the solid mechanics simulation of the mercury spallation target. The proposed methods are used to calibrate the tensile cutoff threshold, mercury density, and mercury speed of sound during intense proton pulse experiments. Using strain experimental data from the mercury target sensors, the newly calibrated simulations achieve 7\% average improvement on the signal prediction accuracy and 8\% reduction in mean absolute error compared to previously reported reference parameters, with some sensors experiencing up to 30\% improvement. The proposed calibrated simulations can significantly aid in fatigue analysis to estimate the mercury target lifetime and integrity, which reduces abrupt target failure and saves a tremendous amount of costs. However, an important conclusion from this work points out to a deficiency in the current constitutive model based on the equation of state in capturing the full physics of the spallation reaction. Given that some of the calibrated parameters that show a good agreement with the experimental data can be nonphysical mercury properties, we need a more advanced two-phase flow model to capture bubble dynamics and mercury cavitation., Comment: 26 pages, 10 figures, 6 tables

Photonic crystals film that possesses periodic dielectric structure have shown great prospect in developing environmentally friendly paper alternatives due to the unique properties of dye free and non-photobleaching, but their practical application is limited by the weak interaction between colloidal particles. Although some progress has been obtained, it is still a challenge to develop photonic paper with the desired mechanical and optical properties. Herein, multifunctional hard core/soft shell nanoparticles with controlled size are fabricated by semi-continuous seed emulsion polymerization method. Compared with convention colloidal particles, these core/shell nanoparticles can facile self-assemble into large-scale dense ordered structure film via dried at room temperature due to the relatively low glass transition temperature (Tg) of the shell layers. The facile fabrication route enables the continuous high-through put production of the photonic papers. The as-formed papers not only possess the capacity to solvent (water/ethanol) rewritable and multicolor painting, but also can rapidly reversible mechanochromic. Moreover, due to the good compatibility of core/shell interface, these photonic films possess excellent mechanical properties, demonstrating that this multifunctional film makes the fabrication of novel robust rewritable papers possible and enables visual monitoring of deformation degree.

Background Recently, the distinction between left- and right-sided colon cancer (LCC and RCC) has been brought into focus. RCC is associated with an inferior overall survival and progression-free survival. We aimed to perform a detailed analysis of the diversity of extracellular vesicles (EV) between LCC and RCC using quantitative proteomics and to identify for new diagnostic and prognostic biomarkers. Methods We isolated EVs from patients with LCC, RCC and healthy volunteers, and treated colorectal cancer cell line with serum-derived EVs. We then performed a quantitative proteomics analysis of the serum-derived EVs and cell line treated with EVs. Proteomic data are available via ProteomeXchange with the identifiers PXD012283 and PXD012304. In addition, we assessed the performance of EV SPARC and LRG1 as diagnosis and prognosis biomarkers in colon cancer. Findings The expression profile of the serum EV proteome in patients with RCC was different from that of patients with LCC. Serum-derived EVs in RCC promoted cellular mobility more significantly than EVs derived from LCC. EV SPARC and LRG1 expression levels demonstrated area under the receiver-operating characteristic curve values of 0.95 and 0.93 for discriminating patients with colon cancer from healthy controls. Moreover, the expression levels of SPARC and LRG1 correlated with tumour sidedness and were predictive of tumour recurrence. Interpretation We identified differences in EV protein profiles between LCC and RCC. Serum-derived EVs of RCC may promote metastasis via upregulation of extracellular matrix (ECM)-related proteins, especially SPARC and LRG1, which may serve as diagnosis and prognosis biomarkers in colon cancer.

Impressive progress has been made on the development of magnesium alloys (Mg) implants in cardiovascular and orthopedic applications due to their good mechanical strength and biodegradable. In this paper, heparin and carboxymethyl chitosan were immobilized on alkali-treated Mg to improve the hemocompatibility and antibacterial activities. Electrochemical tests revealed that the surface modified Mg obviously improved the corrosion resistance. Additionally, the surface-functionalized Mg exhibited excellent antithrombotic and antibacterial activities.

Co-Cr-Fe-Ni-Mn high entropy alloys (HEAs) have attracted extensive attention due to their broad cryogenic engineering application potential, reasonable control of alloying elements can significantly improve its mechanical performance. In this work, the effects of Co content on the phase stability and mechanical behavior CoxCrFeNiMnAl0.3 HEAs were investigated. It is found that with the decrease of the Co content, the stability of the face-centered cubic (FCC) solid solution phase in the alloy decreases, resulting in the precipitation of the BCC (body-centered cubic) phase from the FCC phase, thereby obtaining the FCC + BCC dual-phase structure. During annealing, the precipitated BCC phase can effectively suppress the grain growth and recrystallization of the FCC solid solution, forming an ultrafine-grained microstructure. In addition, the Ni-Al type nano-B2 phase can form in the BCC phase under the influence of the negative formation enthalpy during solidification. This micro/nano hierarchical structure can effectively improve the mechanical properties of the alloys. Co0.25CrFeNiMnAl0.3 maintains relatively excellent tensile yield strength (486 MPa), the tensile elongation remains above 20 %. This study regulates the formation of the BCC phase and B2 phase by reducing the content of Co, which provides a new idea for the preparation of low-cost HEAs with excellent mechanical properties.

Background: Whether extended lymphadenectomy for right colon cancer leads to increased perioperative complications or improves survival is still controversial. This multicentre randomised controlled trial (RCT) aimed to compare the efficacy and safety of complete mesocolic excision (CME) versus D2 dissection in laparoscopic right hemicolectomy for patients with right colon cancer. Methods: This superiority phase III trial was undertaken at 17 hospitals in 9 provinces of China. Patients with adenocarcinoma located between the cecum and the right third of the transverse colon, without evidence of distant metastases, were randomly assigned (in a 1:1 ratio) to receive either CME or D2 dissection during laparoscopic right colectomy. Morbidity and mortality in the first 30 days after surgery were compared between the two groups using a modified intention-to-treat (mITT) analysis. Findings: A total of 1072 patients were enrolled between January 11, 2016, and December 26, 2019. Of these patients, 995 (495 CME patients, 500 D2 patients) were included in the mITT analysis. The 30-day postoperative morbidity rate was 19·6% in the CME group vs. 21·8% in the D2 group (difference, -2·2% [95%CI, -0·07, - 0·03]; P = 0·34); no deaths occurred in either group. The CME procedures harvested significantly more lymph nodes (26·0 vs 23·0, difference, 3·4 [95%CI, 2·0, 4·9]; P

After prosthesis replacement for the treatment of bone tumors, incomplete removal of tumor cells is the main challenge. Moreover, combating implant-associated infection and simultaneously promoting osseointegration are highly demanded for orthopedic implants and therefore, a multifunctional coating that produces tumor therapeutic effects, antibacterial activity, and osteogenesis at the same time is of clinical significance. Herein, a phototherapy platform composed of rare-earth elements - doped titanium dioxide nano-shovel/quercetin/L-arginine (TiO2@UCN/Qr/LA) on titanium bone implant is fabricated. The stable nano-shovel structure prepared by a hydrothermal method improves the photothermal conversion ability of titanium. Incorporation of Yb and Er enhances the upconversion capability, thereby facilitating generation of reactive oxygen species (ROS) during exposure to near-infrared II (NIR-II) light. Furthermore, under the action of ROS, L-arginine is catalyzed to release nitric oxide (NO) free radicals. In vitro and in vivo experiments indicate that the combined actions of ROS, quercetin, and NO not only inhibit bone tumor growth at a temperature of 48 ℃, but also eliminate Staphylococcus aureus biofilms on the Ti implants at a mild temperature of 45 ℃ upon illumination with a 1,060 nm laser. Moreover, TiO2@UCN/Qr/LA promotes angiogenesis and osteogenic differentiation, reduces inflammation, and accelerates formation of new bone tissues.

The surface topography of biomaterials is known to influence cellular response such as adhesion, spreading and differentiation. In this work, the behavior of osteoblasts and endothelial cells on nano-structured Zr and micro/nano-structured ZrO2 alloyed layers of Ti-6Al-4V (TC4) was investigated. Zr alloyed layer (Zr@TC4) decreases the hydrophilicity whereas ZrO2 alloyed layers (ZrO2@TC4) is more hydrophilic than TC4 and more proteins adsorb on ZrO2@TC4 followed by Zr@TC4. The cells proliferate steadily on the smooth TC4 and nano-structured Zr@TC4 surfaces and the osteoblast activity is more pronounced on Zr@TC4 than TC4. The micro/nano-structured surface on ZrO2@TC4 restricts cellular adhesion and spreading independent of the surface wettability and protein adsorption. The findings provide insights into the design of micro/nano-structured biomaterials and interfaces with controlled tissue response.

Ti-6Al-4V (TC4) has received increasing attention as biomaterial but also raised concerns about the long-term safety of releasing of metal ions and poor wear resistance. In this work, an ZrO2/TiO2 alloyed layer was prepared on TC4 by plasma surface alloying with Zr and subsequently annealed in the air for improved corrosion and wear resistant. To assess the corrosion performance of the alloyed layer, the specimens were measured by open circuit potential, electrochemical impedance spectroscopy and potentiodynamic polarization in simulated body fluid solution. The result shows that the ZrO2/TiO2 alloyed layer exhibits strikingly high polarization resistance, wide passive region and very low current density, indicating the excellent corrosion resistance. The layer also displays significant improvement of wear resistance. Furthermore, the alloyed layer restricts cell adhesion and spreading. We infer that the ZrO2/TiO2 alloyed layer might be potentially useful implanted devices such as biosensors, bioelectronics or drug delivery devices.

In this work, TiO 2 /CuO coating was prepared on titanium (Ti) by combination of magnetron sputtering and annealing treatment. The microstructure, biocompatibility, corrosion resistance and antibacterial property of TiO 2 /CuO coating were investigated in comparison with pure Ti and TiO 2 coating. The results show that TiO 2 /CuO coating is mainly composed of TiO 2 and CuO. In vitro cytocompatibility evaluation suggests that no obvious toxicity appears on the TiO 2 /CuO coating, and the coating stimulates the osteoblast spreading and proliferation. Compared with Ti and TiO 2 coating, TiO 2 /CuO coating exhibits improved corrosion resistance and antibacterial ability against S.aureus. This study is the first attempt to apply the combination of magnetron sputtering and annealing treatment to introduce the Cu into TiO 2 coating for surface modification of Ti-based implant materials, which may provide a research foundation for further development of bioactive multifunctional coatings to meet the better clinical demand.

A 31-year-old woman with epigastric pain underwent a “pi”-shaped copper bearing intrauterine device placement 11 years prior while lactating approximately 14 months after delivery. The patient experienced intermittent epigastric pain caused by the intrauterine device penetrating through the gastric wall. Removal required partial gastrectomy.

Staphylococcus aureus (S. aureus) infections resistant to a variety of drugs have been increasingly documented in recent years. Drug resistance has appeared largely due to extensive use of antibiotics. Nisin has been widely used in food industry to prevent bacterial growth. However, nisin resistance has been found in several foodborne pathogenic bacteria. p-Anisaldehyde (AS), an extract from Pimpinella anisum seeds, is a very common digestive herb of north India. In this study, synergistic interactions of nisin combined with AS against S. aureus were observed. The synergy was confirmed by checkerboard microdilution method, with the fractional inhibitory concentration index values ranging from 0.25 to 0.375. The positive interactions were verified by the challenge tests in pasteurized milk and agar diffusion assays. In addition, when treatment with nisin or AS alone or in combination, an obvious loss of 260 nm absorbing materials was observed. And flow cytometry assay showed that nisin or AS alone or in combination caused bacterial membrane permeabilization. The LIVE/DEAD BacLight experiment, scanning electron microscope and transmission electron microscopy observation further confirmed that the compounds could kill bacteria via disrupting membranes. All results above verified that the combination of nisin and AS which showed antibacterial activity by a membrane damage mechanism could not only reduce drug resistance but also be used as a new promising naturally sourced food preservative.

The construction, analysis, and application of reduced-basis methods for uncertainty quantification problems involving nonlocal diffusion problems with random input data is the subject of this work. Because of the lack of sparsity of discretized nonlocal models relative to analogous local partial differential equation models, the need for reduced-order modeling is much more acute in the nonlocal setting. In this effort, we develop reduced-basis approximations for nonlocal diffusion equations with affine random coefficients. Efficiency estimates of the proposed greedy reduced-basis methods are provided. Numerical examples are used to illustrate the effect varying various model parameters have on the efficiency and accuracy of the reduced-basis method relative to sparse-grid interpolation using the full finite element method. It is shown that the proposed reduced-basis approach can indeed provide substantial savings over standard sparse-grid methods.

A large amount of NO is generated through the inducible nitric oxide synthase (iNOS) pathway from the vascular adventitia in various vascular diseases. However, it is currently not fully understood how the iNOS signaling pathway is activated. In the present study, this question was addressed in the context of adventitial cellular interactions. A rat model of acute hypertension in the contralateral carotid arteries was established through transverse aortic constriction (TAC) surgery. In this model, activated macrophages were found surrounded by a large quantity of iNOS-expressing adventitial fibroblasts (AFs), suggesting a possible causal relationship between macrophages and iNOS activation of the neighboring AFs. In an in vitro model, a macrophage-like cell line RAW 264.7 was first activated by LPS treatment. The supernatant was then harvested and applied to treat primary rat AFs. iNOS in AFs was activated robustly by the supernatant treatment but not by LPS itself. Treating AFs with interleukin-1β (IL-1β) also activated iNOS signaling, suggesting that the IL-1β pathway might be a possible mediator. As a consequence of the iNOS activation, total protein nitration and S-nitrosylation significantly increased in those AFs. Additionally, increased deposition of type I and type III collagens was observed in both in vitro and in vivo models. The collagen deposition was partially restored by an iNOS inhibitor, 1400 W. These findings highlight the importance of iNOS signaling during vascular inflammation, and advance our understanding of its activation through a cellular interaction perspective.

Objective: To evaluate the changes of pulmonary tuberculosis in diabetic and non-diabetic patients by CT scanning before and after anti-tuberculous therapy. Methods: Chest CT scans in 71 adult patients with active post primary tuberculosis were reviewed. Among them, 41 had no underlying disease, but 30 were diagnosed with diabetes mellitus. CT scans were performed before and after anti-tuberculous therapy. The initial CT findings as well as the findings in follow-up re-examinations were compared. Statistical analysis was performed using SPSS version 17.0 and p value 0.05). After 6 month anti-tuberculous therapy, the detection rate of most of the lesions by CT, such as consolidation, nodules, bud-in-tree sign, singular and multiple cavities, and pleural effusion, showed statistical significance (p

Recent advances in antibacterial technology has made it possible to obviate the needs for antibiotics to combat bacterial infection during would healing. However, few current wound dressings can simultaneously kill bacteria efficiently and promote would healing by facilitating revascularization. Herein, a hybrid hydrogel embedded with CuS@MoS2 microspheres is synthesized. This hydrogel exhibits outstanding antibacterial activities in a short time and enhances wound healing at the same time. Within 15 min, 99.3% of Escherichia coli (E. coli) and 99.5% of Staphylococcus aureus (S. aureus) are killed due to the synergistic effects rendered by the photodynamic and photothermal antibacterial treatments under co-irradiation of 660 nm visible light (VL) and 808 near infrared (NIR) light. The synergistic effects rendered by hyperthermia and reactive oxygen species (ROS) generated by the hydrogel during light irradiation improves the bacterial membrane permeability so that the bacterial membrane and protein can be easily destroyed by ROS, leading to rapid killing of bacteria in vitro and in vivo. In addition, the CuS@MoS2-incorporated hydrogel expedites wound healing because of promotion of the hypoxia inducible factor-1 (HIF-1α) and vascular endothelial growth factor (VEGF) expression and subsequent vascularization at the wound sites. This safe and synergistic therapy system has large potential in bacteria-infected wound healing therapy.

Biocompatible implant materials with enhanced antibacterial activity, osteogenic and angiogenic capacity are beneficial to osseointegration. Based on the outstanding antimicrobial activity of copper (Cu) and bone-related element silicon (Si), the microporous TiO2 coatings (M-Ti) doped with Cu2+ (M-Cu) and different doses of Si2+ (M-CuSi) were directly fabricated via the simple one-step micro-arc oxidation (MAO). M-Cu causes obvious toxicity towards osteoblasts (OBs) and endothelial cells (ECs) while maintaining excellent antimicrobial activity. By doping Si, it is able to compensate the cytotoxicity of Cu and simultaneously further enhance the activity of OBs and ECs by the synergic stimulatory effects with Cu2+, thus forming a balance between the antibacterial property and biocompatibility. In vitro experiments indicated that the M-CuSi5 coating not only shows good antibacterial properties towards Staphylococcus aureus (S. aureus), but also promotes attachment, spreading, proliferation and differentiation of both OBs and ECs. The most suitable release amount of Cu2+ and Si2+ from M-CuSi5 coating can cause distinctly synergistic stimulatory effects on osteogenesis and angiogenesis by facilitating the osteogenic-related genes and angiogenic-related genes expression. In vivo Micro-CT evaluation and histological observations further mirror that the M-CuSi5 coating results in ameliorative osseointegration, thus being attractive candidate as the bone implant material.

In this work, we suggest a chitosan-modified popcorn-like Au–Ag nanoparticles (CSPNPs) based assay for high sensitive detection of melamine, in which CSPNPs not only provide with an intrinsic peroxidase-like activity but also act as surface enhanced Raman scattering (SERS) substrates. CSPNPs can catalyze the oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB) by H 2 O 2 to the charge transfer complex (CTC), which contributes to a tremendous surface-enhanced resonant Raman scattering (SERRS) signals with 632.8 nm laser excitation. The target molecule melamine can generate an additional compound with H 2 O 2 , which means the available amount of H 2 O 2 for the oxidation of TMB reduced. Correspondingly, the SERRS intensity of CTC is decreased. The decreased Raman intensity is proportional to the concentration of melamine over a wide range from 10 nM to 50 μM ( R 2 =0.989), with a limit of detection (LOD) of 8.51 nM. Moreover, the proposed highly selective method is fully capable of rapid, separation-free detection of melamine in milk powder.

We consider split-step Milstein methods for the solution of stiff stochastic differential equations with an emphasis on systems driven by multi-channel noise. We show their strong order of convergence and investigate mean-square stability properties for different noise and drift structures. The stability matrices are established in a form convenient for analyzing their impact arising from different deterministic drift integrators. Numerical examples are provided to illustrate the effectiveness and reliability of these methods., Comment: 31 pages, 38 figures

Parkinson's disease (PD) is a common neurodegenerative disease characterized by the selective loss of the dopaminergic (DA) neurons in substantia nigra. The degeneration leads to decreased levels of DA in striatum and causes uncontrolled firing of innervated medium spiny neurons (MSNs), thus preventing the patient to act smoothly. Gene-specific deficient mouse models for the recessive forms of PD were generated in the past decade, although most failed to exhibit degeneration of DA neurons or decreased DA level, as evidenced in PD patients. Here by using DJ-1-knockdown neuroblastoma SH-SY5Y cells and Neuro-2a cells as well as DJ-1-deficient mice, we found DJ-1 deficiency could downregulate β-tubulin III via a hypoxia-inducible factor 1α (HIF-1α) pathway, and, correspondingly, we observed reduced microtubule dynamics. With Golgi-Cox impregnation, we also observed declined dendritic complexity and the loss of dendritic spines in striatal MSNs of DJ-1-deficient mice. Our results revealed a novel role of DJ-1 in the regulation of microtubule dynamics and suggested that striatal impairments may also play an important role as loss of DA neurons in the pathogenesis of PD.

In this paper, we investigate the maximum likelihood estimation for the reflected Ornstein–Uhlenbeck (ROU) processes based on continuous observations. Both the cases with one-sided barrier and two-sided barriers are considered. We derive the explicit formulas for the estimators, and then prove their strong consistency and asymptotic normality. Moreover, the bias and mean square errors are represented in terms of the solutions to some PDEs with homogeneous Neumann boundary conditions. We also illustrate the asymptotic behavior of the estimators through a simulation study.

In this study, β-carotene, a resonance Raman active substance, was introduced into the large pore channel of rod-like SBA-15 for the first time. This novel resonance Raman active material has been characterized by small angle X-ray scattering (SAXS) and Brunauer–Emmett–Teller (BET) surface area analysis. The adsorption process did not show any influence on the microstructure of SBA-15 as well as its physicochemical characters. Excited by 514.5 nm laser, the resonance Raman signals of the products were demonstrated as well-defined Raman peaks at 1009, 1158 and 1514 cm −1 , which should be assigned to the methyl rock (C–CH 3 ), carbon single-bond stretch (C–C) and carbon double-bond stretch (C C) normal modes, respectively. In addition, the internal standard method was utilized by resonance Raman spectroscopy to determine the adsorption capacity of mesoporous silicas for β-carotene using the results of UV–vis spectroscopy as a reference.