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The proteasome has been validated as an anticancer drug target, while the role of a subunit of proteasome, PSMC6, in lung adenocarcinoma (LUAD) has not been fully unveiled. In this study, we observed that both the RNA and protein of PSMC6 were highly upregulated in LUAD compared with the adjacent normal tissues. Moreover, a high PSMC6 expression was associated with poor prognosis. In accordance with this finding, PSMC6 was associated with poor tumor differentiation. Furthermore, the silence of PSMC6 by small interference RNAs (siRNAs) could significantly inhibit cell growth, migration, and invasion in lung cancer cell lines, suggesting that PSMC6 might serve as a promising therapeutic target in LUAD. To further explore the molecular mechanism of PSMC6 in LUAD, we observed that the proteasome subunits, such as PSMD10, PSMD6, PSMD9, PSMD13, PSMB3, PSMB1, PSMA4, PSMC1, PSMC2, PSMD7, and PSMD14, were highly correlated with PSMC6 expression. Based on the gene set enrichment analysis, we observed that these proteasome subunits were involved in the degradation of AXIN protein. The correlation analysis revealed that the positively correlated genes with PSMC6 were highly enriched in WNT signaling-related pathways, demonstrating that the PSMC6 overexpression may activate WNT signaling via degrading the AXIN protein, thereby promoting tumor progression. In summary, we systematically evaluated the differential expression levels and prognostic values of PSMC6 and predicted its biological function in LUAD, which suggested that PSMC6 might act as a promising therapeutic target in LUAD.

Icariside I, the glycosylation product of icaritin, is a novel effective anti-cancer agent with immunological anti-tumor activity. However, very limited natural icariside I content hinders its direct extraction from plants. Therefore, we employed a computer-aided protein design strategy to improve the catalytic efficiency and substrate specificity of the α-L-rhamnosidase from Thermotoga petrophila DSM 13995, to provide a highly-efficient preparation method. Several beneficial mutants were obtained by expanding the active cavity. The catalytic efficiencies of all mutants were improved 16–200-fold compared with the wild-type TpeRha. The double-point mutant DH was the best mutant and showed the highest catalytic efficiency (kcat/KM: 193.52 s−1 M−1) against icariin, which was a 209.76-fold increase compared with the wild-type TpeRha. Besides, the single-point mutant H570A showed higher substrate specificity than that of the wild-type TpeRha in hydrolysis of different substrates. This study provides enzyme design strategies and principles for the hydrolysis of rhamnosyl natural products.

Nasopharyngeal carcinoma (NPC) is not only a common malignant disease of the head and neck, but also presented as locoregionally advanced NPC at diagnosis with poor prognosis. The efficacy of current chemoradiotherapy is unsatisfactory; therefore, in this study, we evaluated the safety and efficacy of treating locally advanced NPC using recombinant human endostatin injection (Endostar), combined with a cisplatin plus 5-fluorouracil (PF) regimen and sequential intensity-modulated radiotherapy (IMRT), and compared it with PF plus IMRT regimen. This phase II study included 83 eligible patients with stages III-IVa NPC (8th AJCC/UICC) who were randomized 1:1 into control (n = 42) and experimental (n = 41) groups. The control group received PF chemotherapy and IMRT for locally advanced NPC; One cycle of induction chemotherapy (IC) was administered before IMRT, and three cycles of adjuvant chemotherapy (AC) were administered four weeks post-radiotherapy. The experimental group received additional Endostar therapy. All patients were followed up for at least 5 years. The primary endpoints were progression-free survival (PFS) and the objective response rate. The secondary endpoints included overall survival and treatment-related toxicities. The short-term efficacy was evaluated at the end of the fourth chemotherapy cycle. Our results showed that the complete response rate of nasopharyngeal lesions was not significantly different between the experimental and control groups (80.5 vs. 71.4%, P = 0.335); however, there were significant differences in the complete response rates of cervical metastatic lymph nodes (75.6 vs. 40.5%, P = 0.001), especially for cervical N3 lymph nodes in the experimental group (55.6 vs. 9.5%, P = 0.004). The overall median follow-up time was 69.7 months. Patients in the experimental group showed significantly prolonged PFS by about four months (hazard ratio [HR] = 0.64, 95% CI: 0.41-0.99, P = 0.045). There was no significant difference in the median overall survival (P = 0.374). Furthermore, subgroup analysis indicated that the risk of death in patients with cervical N3 lymph nodes in the experimental group was reduced by 52% (HR = 0.48, 95% CI: 0.23-0.99, P = 0.046). Moreover, the incidence of radiation-induced grades 3-4 oral mucositis was significantly lower in the experimental group (29.3% vs. 54.8%, P = 0.019), while no significant differences in other severe adverse reactions were observed between the two groups (P>0.05). Taken together, our study indicated that, in patients with locally advanced NPC, Endostar in combination with PF chemotherapy and sequential IMRT significantly improved PFS, had tolerable treatment-related toxicities, improved the prognoses of patients with cervical N3 lymph nodes, and reduced the incidence of radiation-related oral mucositis.

In this paper, we study a strong limit theorem of delayed sums for Markov chains in bi-infinite environments by constructing a sequence of random variables with parameters. As a corollary, we obtai...

OBJECTIVE: To explore the optimal maintenance dose of caffeine citrate for preterm infants requiring assisted ventilation and caffeine citrate treatment. METHODS: A retrospective analysis was performed on the medical data of 566 preterm infants (gestational age ≤34 weeks) who were treated and required assisted ventilation and caffeine citrate treatment in the neonatal intensive care unit of 30 tertiary hospitals in Jiangsu Province of China between January 1 and December 31, 2019. The 405 preterm infants receiving high-dose (10 mg/kg per day) caffeine citrate after a loading dose of 20 mg/kg within 24 hours after birth were enrolled as the high-dose group. The 161 preterm infants receiving low-dose (5 mg/kg per day) caffeine citrate were enrolled as the low-dose group. RESULTS: Compared with the low-dose group, the high-dose group had significant reductions in the need for high-concentration oxygen during assisted ventilation (P=0.044), the duration of oxygen inhalation after weaning from noninvasive ventilation (P0.05). CONCLUSIONS: This pilot multicenter study shows that the high maintenance dose (10 mg/kg per day) is generally beneficial to preterm infants in China and does not increase the incidence rate of common adverse reactions. For the risk of feeding intolerance, further research is needed to eliminate the interference of confounding factors as far as possible.

To develop and validate a radiomics-based model for predicting radiation-induced temporal lobe injury (RTLI) in nasopharyngeal carcinoma (NPC) by pretreatment MRI of the temporal lobe.A total of 216 patients with diagnosed NPC were retrospectively reviewed. Patients were randomly allocated to the training (n = 136) and the validation cohort (n = 80). Radiomics features were extracted from pretreatment contrast-enhanced T1- or fat-suppressed T2 weighted MRI. A radiomics signature was generated by the least absolute shrinkage and selection operator (LASSO) regression algorithm, Pearson correlation analysis, and univariable logistic analysis. Clinical features were selected with logistic regression analysis. Multivariable logistic regression analysis was conducted to develop three models for RTLI prediction in the training cohort: namely radiomics signature, clinical variables, and clinical-radiomics parameters. A radiomics nomogram was used and assessed with respect to calibration, discrimination, reclassification, and clinical application.The radiomics signature, composed of two radiomics features, was significantly associated with RTLI. The proposed radiomics model demonstrated favorable discrimination in both the training (AUC, 0.89) and the validation cohort (AUC, 0.92), outperforming the clinical prediction model (p0.05). Combining radiomics and clinical features, higher AUCs were achieved (AUC, 0.93 and 0.95), as well as a better calibration and improved accuracy of the prediction of RTLI. The clinical-radiomics model showed also excellent performance in predicting RTLI in different clinical-pathologic subgroups.A radiomics model derived from pretreatment MRI of the temporal lobe showed persuasive performance for predicting radiation-induced temporal lobe injury in nasopharyngeal carcinoma.• Radiomics features from pretreatment MRI are associated with radiation-induced temporal lobe injury in nasopharyngeal carcinoma. • The radiomics model shows better predictive performance than a clinical model and was similar to a clinical-radiomics model. • A clinical-radiomics model shows excellent performance in the prediction of radiation-induced temporal lobe injury in different clinical-pathologic subgroups.

Lost circulation often occurs in fractured formations, which was a main technological problem during drilling. Conventional lost circulation material (LCM) was often used to form a plugging zone to prevent fluid loss during drilling. The formed seal was a granular material system composed of LCMs. This paper presented the physical mechanism of the force chain within the plugging zone. The seal performance is related to the properties of LCMs. A device for testing seal performance of LCMs with long fracture was developed. The effects of LCM performance on seal integrity were investigated using a plugging device with long fracture. The results showed that the wide particle size distribution (PSD) of LCMs tended to form a strong force chain network structure within the sealing zone. Increasing the stiffness and roughness of LCMs resulted in higher breaking pressure. The addition of fiber with high length-diameter ratio could improve the shear strength of the sealing zone and form a strong force chain network structure, and it can reduce fluid loss.

This study examines the role of wisdom in the cross-cultural adaptation of Chinese visiting scholars in Canada, as mediated by different coping styles. Path analysis was used to for hypotheses testing. The findings suggest that (1) wisdom measured by 3D-WS and Adult Self-Transcendence Inventory (ASTI), independently had direct correlation with social and psychological adaptation, and positively associated with engaged coping (active coping and proactive–reflective coping); (2) the independent effects of 3D-WS and ASTI on social adaptation, psychological adaptation, and life satisfaction were mediated by proactive–reflective coping; (3) wisdom, when measured by 3D-WS, promoted positive psychological adaptation through decreasing passive coping. This study shows that wisdom is a critical factor affecting cross-cultural adaptation, and the use of proactive–reflective coping is a wise way of handling future life challenges.

Uncoupling protein 1 (UCP1) was found exclusively in the inner membranes of the mitochondria of brown adipose tissue (BAT). We found that UCP1 was also expressed in heart tissue and significantly upregulated in isoproterenol (ISO)-induced acute myocardial ischemia (AMI) rat model. The present study is to determine the underlying mechanism involved in the UCP1 upregulation in ISO-induced AMI rat model. The Ucp1−/− rats were generated by CRISPR-Cas9 system and presented decreased BAT volume. 2-months old Sprague Dawley (SD) wild-type (WT) and Ucp1−/− rats were treated with ISO intraperitoneally 30 mg/kg once a day for 3 consecutive days to establish AMI model. In saline group, the echocardiographic parameters, serum markers of myocardial injury cardiac troponin I (cTnI), creatine kinase isoenzyme MB (CK-MB), oxidant malondialdehyde (MDA), antioxidant superoxide dismutase (SOD) or fibrosis were comparable between WT and Ucp1−/− rats. ISO treatment induced worse left ventricle (LV) hypertrophy, myocardial fibrosis, increased higher cTnI, CK-MB and MDA and decreased lower SOD level in Ucp1−/− rats compared with that of WT rats. Ucp1−/− rats also presented lower myocardial phosphocreatine (PCr)/ATP-ratio, which demonstrated worse cardiac energy regulation defect. ISO treatment induced the phosphorylation of AMP-activated protein kinase (AMPK) activation, subsequently the phosphorylation of mammalian target of rapamycin (mTOR) inhibition and peroxisome proliferators-activated receptor α (PPARα) activation in WT rats, whereas activation of AMPK/mTOR/PPARα pathways significantly inhibited in Ucp1−/− rats. To sum up, UCP1 knockout aggravated ISO-induced AMI by inhibiting AMPK/mTOR/PPARα pathways in rats. Increasing UCP1 expression in heart tissue may be a cytoprotective therapeutic strategy for AMI.

A novel orthogonal frequency-division multiplexing (OFDM) multiple-input multiple-output (MIMO) radar is proposed in this paper in a scenario of coexisting with a communication system. For the purpose of avoiding interference to communication while maintaining MIMO radar's capabilities, such as measuring signal's direction of departure (DOD), a collocated antenna array is divided into several overlapped subarrays. Mutually OFDM waveforms exploiting an orthogonal space-time block code are transmitted through these subarrays to obtain waveform diversity, which can be separated at the radar receiver. A MUSIC-like DOD estimation algorithm and the Cramer–Rao bound of DOD are proposed for overlapped subarrays’ configuration in order to evaluate performance of the beamforming strategy. The beamformer is designed using an optimization technique at cost of maximizing the input SNR of radar while keeping communication rate constant. Due to nonconvexity of the optimization problem, a two-step optimization algorithm is proposed. Simulation experiments validate theoretical analysis of the proposed precoding radar. Experiments also show robustness of the precoding scheme and the ability of balancing the input SNR of radar and the communication rate.

The asymptotic equipartition property is a basic theorem in information theory. In this paper, we study the strong law of large numbers of Markov chains in single-infinite Markovian environment on ...

A new schiff base cobalt(III) complex [N,N′-bis(2′-hydroxyphenylacetone)-o-ethanediamine] cobalt(III) (M3) has been synthesized and characterized by single X-ray crystallography. The cytotoxicity of complex M3 was evaluated against HeLa, LoVo, A549, A549/cis cancer cell lines, and the normal cell lines LO2 by MTT assays. The IC50 is in the range of 6.27-22.68 μM, which is somewhat lower than cisplatin on the basis of platinum molar concentration. Furthermore, anticancer mechanistic studies showed that the complex M3 inhibited cell proliferation by blocking DNA synthesis and then acted on nuclear division of HeLa cells over time. Moreover, western blot analysis indicated M3 dramatically decreased the target protein c-Myc and KLF5 expression levels, and activated many signaling pathways including ER stress, apoptosis, cell cycle and DNA damage in HeLa. M3 did not affect proteasomal activity.

A new Schiff base copper(II) complex [N,N′-bis(2′-hydroxyphenylacetone)-o-ethanediamine] copper (II) (M1) has been synthesized and characterized by single X-ray crystallography. The cytotoxicity of complex M1 was evaluated against HeLa, LoVo, A549, A549/cis cancer cell lines, and the normal cell lines LO2 and HUVEC, by MTT (3-(4,5-dimethylthiazoyl-2-yl)2,5-diphenyltetrazoliumbromide) assays. The IC50 (50% inhibition concentrations) is in the range of 5.13–11.68 μM, which is somewhat lower than cisplatin on the basis of platinum molar concentration. Furthermore, anticancer mechanistic studies showed that the complex M1 inhibited cell proliferation by blocking DNA synthesis and then acted on nuclear division of HeLa cells over time. Moreover, M1 increased intracellular ROS (Reactive oxygen species) levels in a dose-dependent manner. Western blot analysis indicated M1 dramatically decrease c-Myc transcription factor and KLF5 (Kruppel-like factor 5) protein expression levels in HeLa. M1 did not inhibit proteasomal activity. Finally, M1 induced DNA damages and activated the DNA damage repair pathways.

Background Gastrointestinal injury is a common complication in patients treated with antiplatelet agents after percutaneous coronary intervention (PCI). However, the effects of different antiplatelet regimens on the incidence and severity of gastrointestinal injury have not been well studied, principally due to the lack of a low-risk sensitive and accurate detection system. Trial design OPT-PEACE is a multicenter, randomized, double-blind, placebo-controlled trial. Gastrointestinal injury will be evaluated with the ANKON magnetically controlled capsule endoscopy system (AMCE), a minimally invasive approach for detecting mucosal lesions in the stomach, duodenum and small intestine. Patients without AMCE-detected gastrointestinal erosions, ulceration or bleeding after drug-eluting stent implantation are enrolled and treated with open-label aspirin (100 mg/d) plus clopidogrel (75 mg/d) for 6 months. Thereafter, 480 event-free patients will undergo repeat AMCE and are randomly assigned in a 1:1:1 ratio to receive aspirin plus clopidogrel, aspirin plus placebo or clopidogrel plus placebo for an additional 6 months. A final AMCE is performed at 12 months. The primary endpoint is the incidence of gastric or intestinal mucosal lesions (erosions, ulceration, or bleeding) within 12 months after enrollment. Conclusions OPT-PEACE is the first study to investigate the incidence and severity of gastrointestinal injury in patients receiving different antiplatelet therapy regimens after stent implantation. This trial will inform clinical decision-making for personalized antiplatelet therapy post-PCI.

In this paper, a joint communication interference integration signal waveform is proposed to satisfy the need of electronic system integration in civil and military uses, and mitigate the tension of spectrum resource. We design the system structure of the integrated signal model and propose the communication receiving processing flow of the integrated system. We utilize the dense false-target jamming style to raise the constant false alarm rate detection threshold via the delay superposition of multiple groups of frequency modulation (FM) slope mismatch jamming signals, which can play a role in protecting our target from being detected. Furthermore, linear frequency modulation (LFM) signals with different FM slopes and Doppler frequencies are obtained via the modulation mapping of communication data; thus, a single LFM signal can carrynbit data. Through correlation processing and frequency detection, code sequence information can be obtained to achieve communication function. The simulation results show that the integrated signal has the effect of shielding and jamming the pulse compression radar. Moreover, the system has a better bit error rate and a high communication rate, which can ensure that the communication task of sending accurate instructions is completed while implementing effective interference.

In this paper, two methods based on PSO algorithm and interval sequence conversion model or interval analysis theory are proposed to identify two kinds of uncertain parameters of a cannon counter-recoil mechanism during the manual recoil and forward moving process. Before identifying, some test data were obtained during the manual recoil process. Then, the uncertain parameters were described by interval number and a mathematical model about recoil process of a cannon was built. Taking the similarity degree of time-series data as an optimization objective function, Particle Swarm Optimization (PSO) algorithm was used to solve the deterministic optimization problem which was transformed by interval sequence conversion model, and the parameter identification of recuperator in the manual recoil process of a cannon was achieved. On this basis, combining PSO algorithm and Krawczyk algorithm of interval analysis theory, the uncertain parameters of recoil brake were identified. Finally, the results of identification proved that the above-mentioned two methods had a relatively high identification accuracy.

A bi-functional ternary nanocomposite was developed by decorating TiO2 and gold nanoparticles on the reduced graphene oxide nanosheets (TiO2-Au-rGO) for recyclable surface enhanced Raman scattering (SERS) detection. TiO2-Au-rGO nanocomposites have been shown to demonstrate the superior SERS performances, which can be used for highly sensitive detection of rhodamine 6 G with a limit of detection of 1.2 × 10−10 M. Subsequently, the surface can be cleaned automatically by the photocatalytic degradation of the adsorbed analytes into inorganic small molecules under visible light irradiation. This can be attributed to the excellent photocatalytic degradation ability, leading to a recyclable SERS application. After being used four times, their excellent SERS and catalytic performances can still be retained. These results suggest that the TiO2-Au-rGO nanocomposites can provide a new strategy for fabricating recyclable SERS substrates, which are highly desirable for SERS practical application.

This study was designed to investigate the protective effect of curcumin againstd-galactose (d-gal)-induced premature ovarian failure (POF) in mice. A mouse POF model was induced by subcutaneous injection ofd-gal (200 mg/kg/day) daily for 42 days. Mice in the curcumin group received bothd-gal treatment and intraperitoneal injection of curcumin (100 mg/kg/day) for 42 days. Ovarian function, oxidative stress and apoptosis were evaluated. The P, E2 and SOD levels were higher, and the FSH, LH and MDA levels were significantly lower in the curcumin group than those in thed-gal group. The proportion of primordial follicles was also significantly higher in the curcumin group than that in thed-gal group. In addition, curcumin treatment afterd-gal administration resulted in significantly lowerSod2,Cat, 8-OhdG, 4-HNE, NTY and senescence-associated protein P16 expression levels, higherAmhexpression levels and less apoptosis in granulosa cells than was observed in thed-gal group. Moreover, the p-Akt, Nrf2 and HO-1 protein expression levels were significantly higher and the apoptosis-related cleaved caspase-3 and -9 protein expression levels were markedly lower in the curcumin group than in thed-gal group. In conclusion, curcumin effectively inhibitedd-gal-induced oxidative stress, apoptosis and ovarian injury via a mechanism involving the Nrf2/HO-1 and PI3K/Akt signaling pathways, suggesting that curcumin is a potential protective agent against POF.

Herein, a zwitterionic Gemini VES (named VES-C) with double ultra-long hydrophobic tails was designed and synthesized which aimed to construct WLM net-structures in high-salinity aqueous solution. Due to the carboxylic group on the spacer, it exhibits partial carboxyl betaine properties and performs well in high salinity environment. Molecular dynamic simulation was carried out and RDF curves were analyzed to predict and explain the mechanism of salinity tolerance of VES-C. Compared with cationic Gemini VESs, a series of experiments were conducted by varying salinity, including surface tension, DLS, 1H NMR and fluorescent probe, to explain the salt-tolerance mechanism of VES-C. The salinity cloudy point of VES-C surpasses 10 wt%, exhibiting superior salt-tolerance to those cationic Gemini VESs. Trough viscosity measurement, oscillatory measurement and microstructure observation, it proves that VES-C molecules can construct WLM netlike structures within the salinity range from 3 wt% to 10 wt% (optimal salinity: 4 wt%), thus VES-C can be applied as the clean thickener to prepared seawater or brine based fracturing fluid by constructing WLM netlike structure in high salinity aqueous environment, which leaves the preparation of clean fracturing fluid independent of freshwater resources.

Objective: To investigate the regulating effect of liraglutide therapy on metabolic disorders in patients with newly diagnosed type 2 diabetes complicated with obesity. Methods: A total of 118 patients with newly diagnosed type 2 diabetes complicated with obesity who were treated in the hospital between September 2014 and January 2017 were collected and divided into the control group (n=59) and observation group (n=59) by random number table. Control group received metformin therapy and the observation group received liraglutide therapy. The differences in levels of glucose metabolism indexes, lipid metabolism indexes and inflammatory factors were compared between the two groups before and after 4 months of treatment. Results: Before treatment, the differences in serum levels of glucose metabolism indexes, lipid metabolism indexes and inflammatory factors were not statistically significant between the two groups. after 4 months of treatment, serum FPG, FIN, F-CP, TC, TG, IL- 1β, IL-6, CRP and TNF-α levels of both groups of patients were lower than those before treatment while HDL-C levels were higher than those before treatment, and serum FPG, FIN, F-CP, TC, TG, IL-1β, IL-6, CRP and TNF-α levels of observation group were lower than those of control group while HDL-C level was higher than that of control group. Conclusion: Liraglutide therapy can effectively optimize the glucose lipid metabolism and reduce the microinflammatory response in patients with type 2 diabetes mellitus complicated with obesity.

The aim of this study was to investigate the protective role and underlying mechanisms of curcumin on glycerol-induced acute kidney injury (AKI) in rats. Glycerol (10 ml/kg BW, 50% v/v in sterile saline, i.m.) was used to induce AKI, followed by curcumin (200 mg/kg/day, p.o.) administration for 3 days. To confirm renal damage and the effects of curcumin on AKI, serum BUN, Scr, and CK as well as renal SOD, MDA, GSH-Px were measured. Additionally, morphological changes were identified by H&E staining and transmission electron microscopy. The expression of several factors including chemotactic factor MCP-1, proinflammatory cytokines including TNF-α and IL-6, as well as the kidney injury markers, as Kim-1 and Lipocalin-2 were also assessed using q-PCR. Finally, cell apoptosis in renal tissue was detected using in situ TUNEL apoptosis fluorescence staining and expression of proteins associated with apoptotic, oxidative stress and lipid oxidative related signaling pathways were detected using immunohistochemical staining and western blot. The results showed that curcumin exerts renoprotective effects by inhibiting oxidative stress in rhabdomyolysis-induced AKI through regulation of the AMPK and Nrf2/HO-1 signaling pathways, and also ameliorated RM-associated renal injury and cell apoptosis by activating the PI3K/Akt pathway.

A series of 10-substituted-3,3,6,6-tetramethyl-9-aryl-3,4,6,7,9,10-hexahydroacridine-1,8(2H,5 H)-dione derivatives 2 were synthesized by reaction of compounds 1 with amines. The compounds 1 were effectively prepared by 5,5-dimethylcyclohexane-1,3-dione and aldehydes in the presence of a little amount of L-proline as catalyst at room temperature. All the compounds were characterized by IR, MS, and 1H NMR. The crystal data of 1b and 2d were collected by X-ray single-crystal diffraction, and compounds 2b and 2d exhibited better inhibitory activity against HepG2 cells.

Graphene, as one of the most promising new materials, has a wide range of applications in biosensors, super-capacitors and catalysts. Herein, we focus on the covalent and noncovalent modification of both graphene and graphene oxide recently reported, and review the interesting properties, e.g., wider electrical band gap and higher dispersibility. We cover covalent derivatization of graphene and graphene oxide with various species, such as nitrenes, carbenes, aryl intermediates, polymers, biomaterials, carbon materials (fullerenes and carbon nanotubes), and organic molecules. As regards, noncovalent functionalization, we consider π–π interactions, van der Waals forces, ionic interactions, and hydrogen bonding. This review also covers some efforts to achieve tailored functionalization for applications. Finally, we assess the future prospects of covalently and noncovalently modified graphene and graphene oxide (Fig. 1).

A novel ternary nanocomposite consisting of activated carbon (AC) and titanium dioxide (TiO2) decoration in the presence of reduced graphene oxide (TiO2–rGO–AC) was fabricated by a facile hydrothermal synthesis method for use as a high-performance photocatalyst. The as-prepared TiO2–rGO–AC nanocomposites were characterized by X-ray diffraction (XRD), scanning electron microscopy, transmission electron microscopy, and UV–Vis diffuse reflectance spectroscopy. The results demonstrated that the TiO2 and activated carbon were well dispersed on the rGO surface. The photocatalytic performance of the TiO2–rGO–AC nanocomposite was evaluated as a catalyst for the photodegradation of rhodamine B. The degradation rate was 3.4 times higher than that of pure TiO2 under simulated solar light irradiation. The enhancement of photocatalytic performance is attributed to the adsorption of AC which significantly increased the organic molecule concentration near the catalytic surface, allowing the effective transfer and separation of photogenerated electrons. TiO2–rGO–AC photocatalyst is also effective for the degradation of tetracycline in aqueous solution, suggesting wide application of these nanocomposite materials in various fields including air purification and wastewater treatment.

In this paper, we introduce a novel strategy of non-uniform sampling(NUS). Jitters of non-uniform sampling are obtained by improving Linear Random Number Generators (ILRNGs) with bit manipulation. Under the frame of compressed sensing theory, Linear Frequency Modulation (LFM) signal is compressed in sub-Nyquist domain. Then we use the energy aggregation characteristic of Fractional Fourier Transform (FrFT) of chirp signal to accomplish parameter estimation, and finally recover the original chirp. By constructing non-uniform sampling hardware platform, we obtain measured data of samples.

The synthesis and secretion of surfactant proteins (SPs) is an important sign of lung maturation. Furthermore, the morbidity of lung developmental diseases, including respiratory distress syndrome and bronchopulmonary dysplasia which are mainly caused by immature lung development and lack of SPs, is increasing. As is well known, multiple microRNAs (miRs/miRNAs) are able to influence lung development via numerous different signaling pathways. However, few studies examine the association between the miRNAs and lung developmental diseases. A previous study has demonstrated that miR‑431 was significantly (F=33.49; P

To assess the effect of cluster of differentiation (CD47) downregulation on autophagy in hypoxia/reoxygenation (H/R)‑treated H9c2 cardiomyocytes. H9c2 cells were maintained in normoxic conditions (95% air, 5% CO2, 37˚C) without CD47 antibodies, Si‑CD47 or chloroquine (CQ) treatment; H9c2 cells in the H/R group were subjected to 24 h of hypoxia (1% O2, 94% N2, 5% CO2, 37˚C) followed by 12 h of reoxygenation (95% air, 5% CO2, 37˚C). All assays were controlled, triplicated and repeated on three separately initiated cultures. The biochemical parameters in the medium supernatant were measured to evaluate the oxidative stress in cardiomyocytes. The Annexin V‑fluorescein isothiocyanate assay was used to detect the apoptotic rate in the H9c2 cells. Transmission electron microscope, immunofluorescent staining and western blot analysis were performed to detect the effect of the CD47 antibody on autophagic flux in H/R‑treated H9c2 cardiomyocytes. The cardiomyocytic oxidative stress and apoptotic rate decreased and autophagic clearance increased after CD47 downregulation. H/R triggered cell autophagy, autophagosome accumulation and apoptosis in H9c2 cell lines. However, these effects can be attenuated by CD47 downregulation. This study demonstrates its clinical implications in ischemia/reperfusion injury treatment.

Deficiency of surfactant proteins (SPs) is the main cause of respiratory distress syndrome (RDS) and chronic lung diseases. Our previous study demonstrated that miR‑431 was differentially expressed between infants with RDS and infants without RDS using microarray analysis. However, the potential role of miR‑431 in the development of lung function is still unknown. In the present study, the morphological characteristics of lung tissues and the expression levels of miR‑431 were examined at three time points of rat lung development [gestational days 19 and 21 (E19, and E21) and postnatal day (P3)]. The protein and mRNA levels of SMAD4 and SPs (SP‑A, SP‑B, SP‑C and SP‑D) were also validated by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blot analysis, respectively. The expression levels of miR‑431 were gradually decreased over time periods of E19, E21 and P3, as determine using RT‑qPCR and fluorescence in situ hybridization. Dual luciferase‑reporter assays revealed that SMAD4 is a direct target of miR‑431. The mRNA and protein expression levels of SMAD4 and SPs increased gradually in rat lung tissues from E19 to P3. The order of magnitude was as follows: E19, E21 and P3. The present study demonstrated that the expression level of miR‑431 decreased in the order of E19, E21 and P3 during rat lung development. The target gene of miR‑431, SMAD4, was negatively regulated by miR‑431, and its expression levels in the rat lung tissue increased from E19 to the P3. Surfactant synthesis was further increased over the E19 to P3 time period. Further studies are required to determine how miR‑431 regulates pulmonary surfactant synthesis by targeting SMAD4.

The pharmaceutical industry has been undergoing a paradigm shift towards continuous manufacturing, under which novel approaches to real-time product quality assurance have been investigated. A new perspective, entitled Quality-by-Control (QbC), has recently been proposed as an important extension and complementary approach to enable comprehensive Quality-by-Design (QbD) implementation. In this study, a QbC approach was demonstrated for a commercial scale tablet press in a continuous direct compaction process. First, the necessary understanding of the compressibility of a model formulation was obtained under QbD guidance using a pilot scale tablet press, Natoli BLP-16. Second, a data reconciliation strategy was used to reconcile the tablet weight measurement based on this understanding on a commercial scale tablet press, Natoli NP-400. Parameter estimation to monitor and update the material property variance was also considered. Third, a hierarchical three-level control strategy, which addressed the fast process dynamics of the commercial scale tablet press was designed. The strategy consisted of the Level 0 built-in machine control, Level 1 decoupled Proportional Integral Derivative (PID) control loops for tablet weight, pre-compression force, main compression force, and production rate control, and Level 2 data reconciliation of sensor measurements. The effective and reliable performance, which could be demonstrated on the rotary tablet press, confirmed that a QbC approach, based on product and process knowledge and advanced model-based techniques, can ensure robustness and efficiency in pharmaceutical continuous manufacturing.

To explore the efficiency and safety of bivalirudin in patients undergoing emergency percutaneous coronary intervention via radial access.Bivalirudin reduces bleeding risks over heparin in patients undergoing PCI. However, bleeding advantages of bivalirudin in patients undergoing transradial intervention is uncertain.In the BRIGHT trial, 1,723 patients underwent emergency PCI via radial access, with 576 patients in the bivalirudin arm, 576 in the heparin arm and 571 in the heparin plus tirofiban arm. The primary outcome was 30-day net adverse clinical event (NACE), defined as a composite of major cardiac and cerebral events or any bleeding.30-day NACE occurred in 5.7% with bivalirudin, 7.8% with heparin alone (vs. bivalirudin, P = 0.159), and 10.3% with heparin plus tifofiban (vs. bivalirudin, P = 0.004). The 30-day bleeding rate was 0.9% for bivalirudin, 2.3% for heparin (vs. bivalirudin, P = 0.057), and 5.8% for heparin plus tirofiban (vs. bivalirudin, P 0.001). Major cardiac and cerebral events (4.9 vs. 5.7 vs. 4.6%, P = 0.899), stent thrombosis (0.5 vs. 0.5 vs. 0.7%, P = 0.899) and acquired thrombocytopenia (0.2 vs. 0.5 vs. 0.9%, P = 0.257) at 30 days were similar among three arms. The interaction test for PCI access and randomized treatment showed no significance on all bleeding (P 0.05).The bleeding benefit of bivalirudin was independent of artery access. Bivalirudin lead to statistical reduction on bleeding risks in comparison to heparin plus tirofiban, and only small numerical difference in comparison to heparin, with comparable risks of ischemic events and stent thrombosis in patients with acute myocardial infarction (AMI) undergoing emergency transradial PCI. © 2016 Wiley Periodicals, Inc.

Objective To investigate the effect of gender on in-hospital mortality in patients with acute ST-elevated myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). Methods To retrospectively analyze the data collected from the Management System of Cardiovascular Interventional Treatment in Military Hospitals. A total of 8878 consecutive patients with acute STEMI undergoing PPCI were enrolled, including 7137 males and 1741 females. Data were grouped by gender to evaluate the impact of gender difference on the in-hospital mortality, and the impact was further evaluated by a propensity score analysis to adjust the differences of patients' ages in baseline characteristics between females and males. Results Compared with that in male patients, female patients were older (P