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Background: Photodynamic therapy (PDT) is an antitumor therapy and has traditionally been regarded as a localized therapy in itself. However, recent reports have shown that it not only exerts a direct cytotoxic effect on cancer cells but also enhances body's tumor immunity. We hypothesized that the immunological response induced by PDT could potentially enhance the efficacy of programmed death‐1 (PD‐1) / programmed death‐ligand 1 (PD‐L1) blockade. Methods: The cytotoxic effects of PDT on colon 26 cells were investigated in vitro using the WST assay. We investigated whether the antitumor effect of anti‐PD‐1 antibodies could be amplified by the addition of PDT. We performed combination therapy by randomly allocating tumor‐bearing mice to four treatment groups: control, anti‐PD‐1 antibodies, PDT, and a combination of anti‐PD‐1 antibodies and PDT. To analyze the tumor microenvironment after treatment, the tumors were resected and pathologically evaluated. Results: The viability rate of colon 26 cells decreased proportionally with the laser dose. In vivo experiments for combined PDT and anti‐PD‐1 antibody treatment, combination therapy showed an enhanced antitumor effect compared with the control. Immunohistochemical findings of the tumor microenvironment 10 days after PDT indicated that the number of CD8+ cells, the area of Iba‐1+ cells and the area expressing PD‐L1 were significantly higher in tumors treated with combination therapy than in tumors treated with anti‐PD‐1 antibody alone, PDT alone, or the control. Conclusions: PDT increased immune cell infiltration into the tumor microenvironment. The immunological response induced by PDT may enhance the efficacy of PD‐1/PD‐L1 blockade. [ABSTRACT FROM AUTHOR]

Females with existing high‐risk HPV (HR‐HPV) infections remain at risk of subsequent multiple or recurrent infections, on which benefit from HPV vaccines was under‐reported. We pooled individual‐level data from four large‐scale, RCTs of AS04‐HPV‐16/18 vaccine to evaluate efficacy and immunogenicity in females DNA‐positive to any HR‐HPV types at first vaccination. Females receiving the AS04‐HPV‐16/18 vaccine in the original RCTs constituted the vaccine group in the present study, while those unvaccinated served as the control group. Vaccine efficacy (VE) against new infections and associated cervical intraepithelial neoplasia (CIN) 2+ in females DNA‐negative to the considered HR‐HPV type but positive to any other HR‐HPV types, VE against reinfections in females DNA‐positive to the considered HR‐HPV type but cleared naturally during later follow‐up, and levels of anti‐HPV‐16/18 IgG were assessed. Our final analyses included 5137 females (vaccine group = 2532, control group = 2605). The median follow‐up time was 47.88 months (IQR: 45.72‐50.04). For the prevention of precancerous lesions related to the non‐infected HR‐HPV types at baseline, VE against HPV‐16/18 related CIN 2+ was 82.70% (95% CI: 63.70‐93.00%). For the prevention of reinfections related to the infected HR‐HPV types following natural clearance, VE against HPV‐16/18 12MPI was non‐significant (p >.05), albeit robust immunity persisted for at least 48 months. Females with existing HR‐HPV infections at first vaccination still benefit from vaccination in preventing precancers related to the non‐infected types at baseline. VE against reinfections related to the infected types following natural clearance remains to be further investigated. [ABSTRACT FROM AUTHOR]

We described a base‐promoted O‐arylation of N3‐hydroxyl quinazolinones with diaryliodonium salts and sequential BF3 ⋅ OEt2 and visible light‐controlled [3,3]‐ or [1,3]‐rearrangements of quinazolinone N−O aryl moieties to prepare a variety of 2‐(quinazolin‐4‐yloxy)phenols and atropisomeric 3‐(2‐hydroxyphenyl)quinazolin‐4‐ones in 44%‐75% yields and 28%‐70% yields, respectively. Mechanistic studies showed that HBF4 generated in situ from BF3 ⋅ Et2O and water served as the catalyst in this process and aryloxyquinazolinium salts are vital intermediates promoting the [3,3]‐ or [1,3]‐rearrangements. The N−O aryl moieties of aryloxyquinazolinium salts were found to undergo solely [3,3]‐rearrangement with heating whereas [1,3]‐rearrangement occurred via a radical process under irradiation of visible light. This method highlights the formation of aryloxyquinazolinium salts based on the use of BF3 ⋅ OEt2 and visible light to prompt [1,3]‐rearrangement generating atropisomeric quinazolinones. [ABSTRACT FROM AUTHOR]

Sinus macrophages in draining lymph nodes (DLNs) are involved in anti‐tumor immune reactions. CD169 (Sialoadhesin, Siglec‐1) is expressed on sinus macrophages and is considered a surrogate marker for the immunostimulatory phenotype of macrophages. In this study, the significance of sinus macrophages in immunotherapy was evaluated using mouse models. Treatment with anti‐programmed death‐ligand 1 (PD‐L1) antibody suppressed the subcutaneous tumor growth of MC38 and E0771 cells but was not effective against MB49 and LLC tumors. Decreased cytotoxic T‐lymphocyte (CTL) infiltration in tumor tissues and CD169 expression in sinus macrophages were observed in MB49 and LLC cells compared to corresponding parameters in MC38 and E0771 cells. The anti‐tumor effects of the anti‐PD‐L1 antibody on MC38 and E0771 cells were abolished when sinus macrophages in DLNs were depleted, suggesting that sinus macrophages are involved in the therapeutic effect of the anti‐PD‐L1 antibody. Naringin activated sinus macrophages. Naringin inhibited tumor growth in MB49‐ and LLC‐bearing mice but did not affect that in MC38‐ and E0771‐bearing mice. The infiltration of CTLs in tumor tissues and their activation were increased by naringin, and this effect was impaired when sinus macrophages were depleted. Combination therapy with naringin and anti‐PD‐L1 antibody suppressed MB49 tumor growth. In conclusion, CD169‐positive sinus macrophages in DLNs are critical for anti‐tumor immune responses, and naringin suppresses tumor growth by activating CD169‐positive sinus macrophages and anti‐tumor CTL responses. The activation status of sinus macrophages has been suggested to differ among tumor models, and this should be investigated in future studies. [ABSTRACT FROM AUTHOR]

Introduction: Periodontitis is the main indication for dental extraction and often leads to peri‐implantitis (PI). Alveolar ridge preservation (ARP) is an effective means of preserving ridge dimensions after extraction. However, whether PI prevalence is lower after ARP for extraction after periodontitis remains unclear. This study investigated PI after ARP in patients with periodontitis. Materials and Methods: This study explored the 138 dental implants of 113 patients. The reasons for extraction were categorized as periodontitis or nonperiodontitis. All implants were placed at sites treated using ARP. PI was diagnosed on the basis of radiographic bone loss of ≥3 mm, as determined through comparison of standardized bitewing radiographs obtained immediately after insertion with those obtained after at least 6 months. Chi‐square and two‐sample t testing and generalized estimating equations (GEE) logistic regression model were employed to identify risk factors for PI. Statistical significance was indicated by p < 0.05. Results: The overall PI prevalence was 24.6% (n = 34). The GEE univariate logistic regression demonstrated that implant sites and implant types were significantly associated with PI (premolar vs. molar: crude odds ratios [OR] = 5.27, 95% confidence intervals [CI] = 2.15–12.87, p = 0.0003; bone level vs. tissue level: crude OR = 5.08, 95% CI = 2.10–12.24; p = 0.003, respectively). After adjustment for confounding factors, the risks of PI were significantly associated with implant sites (premolar vs. molar: adjusted OR [AOR] = 4.62, 95% CI = 1.74–12.24; p = 0.002) and implant types (bone level vs. tissue level: AOR = 6.46, 95% CI = 1.67–25.02; p = 0.007). The reason for dental extraction—that is, periodontitis or nonperiodontitis—was not significantly associated with PI. Conclusion: ARP reduces the incidence of periodontitis‐related PI at extraction sites. To address the limitations of our study, consistent and prospective randomized controlled trials are warranted. [ABSTRACT FROM AUTHOR]

The role of sinus macrophages (SMs) in anticancer immune responses has received considerable interest in recent years, but the types of molecules that are expressed in human SMs have not yet been clarified in detail. We therefore sought to identify dendritic cell (DC)– or macrophage‐related molecules in SMs in human lymph nodes (LNs). SMs are strongly positive for Iba‐1, CD163, CD169, and CD209. CD169 (clone SP216) reacted with almost all SMs, mainly in the cell surface membrane, while CD169 (clone HSn 7D2) reacted with a subpopulation of SMs, mainly in the cytoplasm, with a significant increase observed after IFN‐α stimulation. The immunoreactivity of clone HSn 7D2 was markedly reduced after transfection with small interfering RNA against CD169, while that of clone SP216 was slightly reduced. The induction of CCL8 and CXCL10 messenger RNA (mRNA) expression by IFN‐α was confirmed using cultured macrophages and RT‐qPCR, but fluorescence in situ hybridization did not detect CCL8 and CXCL10 mRNA expression in SMs. Single‐cell RNA sequence data of LNs indicated that the highest level of CXCL10 gene expression occurred in monocytes. In conclusion, we found that CD209, also known as DC‐related molecule, was expressed in human SMs. The heterogeneity observed in CD169 reacted with cone HSn 7D2 and SP216 was potentially due to the modification of CD169 protein by IFN stimulation. Further, no expression of CXCL10 mRNA in SMs suggested that SMs might be resident macrophages. [ABSTRACT FROM AUTHOR]

Our research interest focusing on synthetic methodology with diaryliodonium salts, is summarized in this account. Besides employing a dual activation strategy of C−I and ortho C−H bonds, we have introduced vicinal functional groups at ortho‐positions of diaryliodonium salts, in which their unique reactivities have been explored in various processes, including arylation, diarylation, cascade annulation, benzocyclization, arylocyclization, and intramolecular aryl migration. The variety of mechanisms of these reactions that involves either transition metals, especially palladium in organometallic catalysis, or transition‐metal free conditions, were discussed in the context. [ABSTRACT FROM AUTHOR]

The rapid development of additive manufacturing has fueled a revolution in various research fields and industrial applications. Among the myriad of advanced 3D printing techniques, two‐photon polymerization lithography (TPL) uniquely offers a significant advantage in nanoscale print resolution, and has been widely employed in diverse fields, for example, life sciences, materials sciences, mechanics, and microfluidics. More recently, by virtue of the optical transparency of most of the resins used, TPL is finding new applications in optics and photonics, with nanometer to millimeter feature dimensions. It enables the minimization of optical elements and systems, and exploration of light‐matter interactions with new degrees of freedom, never possible before. To review the recent progress in the TPL related optical research, it starts with the fundamentals of TPL and material formulation, then discusses novel fabrication methods, and a wide range of optical applications. These applications notably include diffractive, topological, quantum, and color optics. With a panoramic view of the development, it is concluded with insights and perspectives of the future development of TPL and related potential optical applications. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) have recently improved the prognosis of various cancers. By contrast, some immune‐related adverse events (irAEs) caused by ICIs are fatal and have become problematic. The pathogenesis of irAEs remains unknown and must be elucidated to establish biomarkers. This study investigated plasma cytokine, chemokine, and anti‐CD74 autoantibody levels in patients with renal cell carcinoma (RCC) and analyzed their association with irAEs. In a discovery cohort of 13 patients, plasma levels of chemokine (C–X–C motif) ligand (CXCL) 1, IL‐17A, IL‐1β, IL‐6, IL‐8, CXCL10, MCP‐1, and TNFα were measured at baseline and post–dose 1. Only CXCL10, at post–dose 1 but not at baseline, was significantly associated with grade 2 or higher irAEs (P = 0.0413). Plasma CXCL10 levels were then measured at baseline and post–dose 1 in an extended cohort of 43 patients with RCC who received ICI‐based treatment. Higher plasma CXCL10 levels both at baseline and post–dose1 were significantly associated with the occurrence of grade 2 or higher irAEs (P = 0.0246 and 0.0137, respectively). Plasma CXCL13 levels, which we measured in a previous study, were significantly higher in patients with grade 2 or higher irAEs at baseline but not at post–dose 1 (P = 0.0037 and 0.052, respectively). No significant association between plasma anti‐CD74 autoantibody level and both irAE pneumonitis and any grade 2 or higher irAE was observed. In conclusion, plasma CXCL10 is significantly associated with the occurrence of irAEs in patients with RCC treated with ICIs. CXCL10 is a potential predictive and on‐treatment biomarker for irAEs. [ABSTRACT FROM AUTHOR]

Tumor‐associated macrophages (TAMs) are the most prominent immune cells in the breast cancer microenvironment, and the protumor functions of TAMs are thought to affect cancer progression and resistance to anticancer therapy. Numerous studies using human breast cancer samples, cell lines, and murine breast cancer models have revealed details of the mechanisms by which the protumor functions of TAMs are activated. Recent advances have highlighted the significant involvement of TAMs in the resistance of breast cancer cells to immunotherapy. Tumor‐associated macrophages express a number of immunosuppressive genes, and single‐cell sequence analyses of human and murine cancer samples have helped elucidate the mechanism of TAM‐induced immunosuppression. As TAMs are considered suitable targets for anticancer therapies, we summarized the protumor functions of TAMs and the potential of anticancer therapies targeting TAMs, with a focus on breast cancer research. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine the (a) dose–response effects of cognitively engaging movement games (CEMGs) designed to improve aerobic capacity, interference control (IC), and academic performance, (b) relationship between intervention‐induced improvements in aerobic capacity, IC, and academic performance, and (c) moderation effect of IC on the relationship between aerobic capacity and academic performance in overweight children. Seventy‐five overweight children (aged 11.23 ± 0.60 years; 48% males) participated in this study conducted in Taipei during the 2018/2019 academic year and were randomly assigned to the low‐dose (20‐min) intervention, high‐dose (40‐min) intervention, and control groups and completed a Stroop test, half‐mile run, and language and mathematics tests before and after a 10‐week afterschool program. Both intervention groups showed similar improvements in outcomes of aerobic capacity (ds > 0.80), IC (ds > 0.76), and academic performance (ds > 0.90) from the pretest to posttest, whereas these outcomes were unchanged for the control group. Furthermore, improved IC moderated the association between improvements in aerobic capacity and academic performance. Our findings suggest that CEMG with varying doses is feasible and effective for improving aerobic capacity, IC, and academic performance in overweight children and that the association between improvements in aerobic capacity and academic performance depends on the intervention effects on IC. [ABSTRACT FROM AUTHOR]

A variety of functionalized 3‐(2‐hydroxyaryl)indazoles and N‐(tetrahydrofuran‐2‐yl)‐3‐(2‐hydroxyaryl)indazoles were prepared in moderate to good yields through a transition metal‐free radical O‐arylation and sequential [3,3]‐rearrangement cascade strategy from N‐hydroxyindazoles and diaryliodonium salts. The equivalents of diaryliodonium salts controlled the formation of the product structures. Mechanistic studies revealed that the O‐arylation and N−O bond cleavage via [3,3]‐rearrangement involved an intermolecular radical process. The reaction tolerated various sensitive functional groups, such as halides, ester, and aldehyde groups. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to recapitulate the change trajectory of postoperative weight and investigate the association between postoperative hypothalamic damage and weight gain and hypothalamic obesity (HO) in patients with adult‐onset craniopharyngioma. Methods: The data of 96 patients with surgically treated primary adult‐onset craniopharyngioma were retrospectively analyzed. The association between postoperative hypothalamic damage based on magnetic resonance images or endoscopic observation and postoperative weight gain and HO was determined by multivariable logistic regression. Results: Forty‐seven (49.0%) patients and 18 (18.8%) patients experienced clinically meaningful weight gain (≥5%) and HO at last follow‐up, respectively. Postoperative weight significantly increased during the first 6 months following surgery, followed by stabilization. Both grade 2 postoperative hypothalamus damage, as evaluated by the magnetic resonance imaging classification system of Müller et al., and higher scores based on the Roth et al. hypothalamic lesion score were significantly associated with postoperative weight gain of ≥5% (p = 0.005 and p = 0.002) and with HO (p = 0.001 and p = 0.008). Additionally, bilateral hypothalamic injury as evaluated by the Hong et al. hypothalamic injury pattern based on endoscopic observation (p = 0.008) could predict postoperative weight gain ≥5%. Conclusions: Significant postoperative weight gain is common in patients with adult‐onset craniopharyngioma. Postoperative hypothalamic damage can predict clinically meaningful weight gain and HO. [ABSTRACT FROM AUTHOR]

The introduction of solid dielectrics to electrode surfaces will change the motion behaviours of free metallic particles and in turn affect partial discharge (PD) characteristics in transformer oil. To estimate the influence, the metallic particles movement in flowing oil was compared between different cases with and without insulating paper covering electrodes here. When the electrodes were bare, particles executed up‐down movements repeatedly in the vertical direction. As the electrodes were paper‐covered, the particles would settle on the paper surface for a period of time. Simultaneously, the PD characteristics caused by metallic particles were measured. When the electrodes were bare, the discharges concentrated in 0–90° and 300–360° and the PD magnitude reached 390 pC. When the double electrodes were paper‐covered, the PD magnitude decreased by 67% and the concentration phases of PDs would migrate to 45° and 160°. In order to analyse the experimental results, a simulation model with a paper‐covered boundary was constructed. Simulated trajectories of particles were in accord with the experiment results. Base on the model, the particle motion characteristics were obtained and the electric field distribution between the particle and electrode was calculated. Finally, the influence of paper‐covering on PD characteristics was discussed. [ABSTRACT FROM AUTHOR]

BACKGROUND The tea green leafhopper, Empoasca flavescens is the most important pest in Chinese tea plantations. For decades its control has been executed almost exclusively through pesticide applications. A semiochemical‐based 'push–pull' strategy was tested on the leafhopper in the study. RESULTS: The odors released from Tagetes erecta and Flemingia macrophylla significantly repelled and attracted leafhoppers, respectively. These volatile compounds (46 from T. erecta and 53 F. macrophylla) were identified and quantified via gas chromatography–mass spectometry (GC–MS) analysis. Y‐tube olfactometer assays indicated that thymol anisole, thymol and camphor had significant repellent effects on the leafhoppers, resulting in a ternary repellent blend at a 4:3:13 ratio. Cis‐3‐hexen‐1‐ol, cis‐3‐hexenyl acetate, nonanal and α‐farnesene were significantly attractive to the leafhoppers, making an attractant blend at a 17:4:1:1 ratio. In the field, the push–pull strategy with the repellent dispensers placed within the tea bushes and the attractant‐baited sticky traps hung 15 cm above the tea plants showed a significant control efficacy, reaching 69% and 55% at two and 14 days post‐treatment, respectively, similar to those in the insecticide control plots. Additionally, the leafhopper density in the push–pull intercropping plot was 63.2 leafhoppers/100 tea shoots/visit, much lower than those in the pull intercropping plot and nonintercropping plot. CONCLUSION: Application of the push–pull strategy using both synthetic repellent and attractant, or intercropping T. erecta and F. macrophylla with tea plants, can effectively reduce the leafhopper population. This approach might have great potential as an environmentally safe control strategy against the leafhopper. © 2022 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

A variety of pseudorutaecarpine derivatives were prepared in good to excellent yields through a gold(I)‐catalyzed selective cyclization and 1,2‐shift of N‐alkynyl quinazolinone‐tethered indoles. Mechanistic study revealed that spiroindolenines generated in situ by cyclization at the the indole C3 position underwent an alkenyl 1,2‐shift to generate pseudorutaecarpine. The reaction proceeds under mild reaction conditions, has a broad substrate scope, good functional group tolerance, and gram‐scalable application. Furthermore, biological evaluation showed that most of the pseudorutaecarpine scaffolds prepared exhibit anti‐inflammatory activity. [ABSTRACT FROM AUTHOR]

By using diaryliodonium salts, a cylization has been accomplished in the synthesis of N‐aryl phenanthridinone derivatives via a cascade of ortho‐arylation and Csp2‐N bond formation in the presence of palladium catalyst. The reaction exhibits a broad compatibility of readily available N‐arylnaphthamides. [ABSTRACT FROM AUTHOR]

Recently, surface‐enhanced Raman spectroscopy (SERS)‐based detection strategies have been widely developed for various practical applications, due to the near‐single‐molecule sensitivity and fingerprint identification capability. However, the qualitative and quantitative reliability of SERS have always been questioned when comparing with the classical GC/LC–MS techniques. Here, we systematically compared the properties of SERS and LC–MS in the detection of an unexpected herbicide in commercial herbicide. The result showed that, in the case of the ultra‐trace target detection in a complicated matrix, SERS‐based strategy exhibited high sensitivity and a much higher detection efficiency than the LC–MS‐based one, which demonstrated a more accurate quantifiability being facilitated with a well‐controlled sample pretreatment. Therefore, we showed that SERS could be further implemented in fast and on‐site detection tools for food safety application and environment monitoring. [ABSTRACT FROM AUTHOR]

In this study, a simulation model of surface charge accumulation on a basin‐type insulator was constructed. Three accumulation mechanisms were considered, i.e. electrical conduction within the gas, electrical conduction through the insulator and along insulator surface. For the gas electrical conduction, the generation, diffusion, drift and recombination of charge carriers in SF6 were taken into consideration. The surface conductivity is treated by directly defining parameters instead of surface thin layer, which improves the calculation range of surface conductivity in ion flow model. Additionally, surface charge accumulation characteristics with different parameters were studied. The results indicated that the polarity of surface charge would change with the ion pair generation rate, volume conductivity and surface conductivity. Based on the surface charge and electric field distributions, it was found that the dominant surface charge accumulation mechanism changes from volume conduction to gas conduction as the ion pair generation rate increases. When the volume conductivity increases from 1 × 10−19 to 1 × 10−14 S/m, the dominant mechanism changes from gas conduction to volume conduction. Furthermore, as the surface conductivity increases, the dominant mechanism is surface conduction. The proposed study is helpful for understanding the mechanism of surface charge accumulation and provides insight into charge accumulation inhibition. [ABSTRACT FROM AUTHOR]

Partial discharge (PD) characteristics of the transformer oil contaminated by metallic particles are relevant to particle movement. The motion characteristics of the particles will change when the oil flows, and hence, the PD characteristics differ from that in stationary oil. In this study, the PD characteristics were investigated at direct current voltages, and the particle trajectories were observed simultaneously. It was found that the number of discharges obviously decreased, but the discharge magnitude slightly increased as the oil flow speed increased. To explain the changes in the PD characteristics, a solid‐liquid two‐phase flow model was established to simulate the trajectories and the electric field distribution around particles. The experimental observations partially verified the simulated trajectories, which includes two stages, namely sedimentation and the subsequent oscillation‐collision stage. With the increase of the flow speed, the sedimentation particles decreased, and the horizontal spacing between two adjacent particle‐electrode collisions elongated. Therefore, the total collisions became infrequent, which reduced the number of discharges. Moreover, the higher the flow speed was, the slower the particle approached an electrode. Considering the discharge time lag, the distance between the particle and the electrode at the instant of the PD would increase, which increased the discharge magnitude. [ABSTRACT FROM AUTHOR]

Abstarct: The objective was to investigate the upstream mechanisms of apoptosis which were triggered by a novel antimicrotubule drug, ABT‐751, in a tumor protein p53 (TP53)‐deficient hepatocellular carcinoma‐derived Hep‐3B cells. A series of in vitro assays indicated that ABT‐751 caused the disruption of the mitotic spindle structure, collapse of mitochondrial membrane potential, generation of reactive oxygen species, DNA damage, G 2/M cell cycle arrest, inhibition of anchorage‐independent cell growth and apoptosis in Hep‐3B cells accompanied by alteration of the expression levels of several DNA damage checkpoint proteins and cell cycle regulators. Subsequently, ABT‐751 triggered apoptosis along with markedly upregulated several proapoptotic proteins involving in extrinsic, intrinsic, and caspase‐mediated apoptotic pathways. A pan‐caspase inhibitor suppressed ABT‐751‐induced apoptosis. ABT‐751 also induced autophagy soon after the occurrence of apoptosis through the suppression of AKT serine/threonine kinase/mechanistic target of rapamycin signaling pathway. Exogenous expression of the TP53 gene significantly incurred both apoptosis and autophagy in Hep‐3B cells. Pharmacological inhibition of autophagosome (early autophagy) but not autolysosome (late autophagy) enhanced ABT‐751‐induced apoptosis in TP53‐deficient Hep‐3B cells. Our study provided a new strategy to augment ABT‐751‐induced apoptosis in TP53‐deficient cells. A microtubule inhibitor, ABT‐751 induced autophagy and apoptosis in hepatocellular carcinoma (HCC)‐derived tumor protein p53 (TP53)‐deficient Hep‐3B cells. Soon after the occurrence of apoptosis through the suppression of AKT/mechanistic target of rapamycin (MTOR) signaling, ABT‐751‐induced autophagy. Inhibition of the formation of autophagosome but not autolysosome augments ABT‐751‐induced apoptosis. [ABSTRACT FROM AUTHOR]

The objective of this study was to examine the expression level of cytochrome P450 4B1 (CYP4B1) protein and its clinical significance in specimens from patients with urothelial carcinomas (UC) including upper tract urothelial carcinoma (UTUC, n = 340) and urinary bladder urothelial carcinoma (UBUC, n = 295). Data mining on public domains identified five potential candidate transcripts which were downregulated in advanced UBUCs, indicating that it might implicate in UC progression. Immunohistochemistry was performed to analyze the CYP4B1 protein levels on 635 tissues from UC patients retrospectively. Immunoexpression of CYP4B1 was further estimated using the H‐score method. Correlations between CYP4B1 H‐score and important clinicopathological factors, as well as the significance of CYP4B1 expression level for disease‐specific and metastasis‐free survivals were evaluated. In UTUCs and UBUCs, 118 (34.7%) and 92 (31.2%) patients, respectively, were identified to be of CYP4B1 downregulation. The CYP4B1 expression level was found to be associated with several clinicopathological factors and patient survivals. Downregulation of CYP4B1 protein was correlated to advanced primary tumor (p < 0.001), nodal metastasis (p < 0.001), high histological grade (p = 0.001), vascular invasion (p < 0.001), perineural invasion (p = 0.017) and mitotic rate (p = 0.036) in UTUCs and/or UBUCs. Low CYP4B1 protein level independently predicted inferior disease‐specific (p = 0.009; p < 0.001) and metastasis‐free (p = 0.035; p < 0.001) survivals in UTUC and UBUC patients. Our findings showed that downregulation of CYP4B1 protein level is an independent unfavorable prognosticator. Loss of the CYP4B1 gene expression may play an important role in UC progression. [ABSTRACT FROM AUTHOR]

In this study, two types of samples, i.e. a disc‐shaped cavity embedded within solid dielectrics and the other on an electrode surface, were used to investigate partial discharge (PD) behaviours at DC voltage. It has been found that the discharge frequency of the sample with one metallic surface was much larger under a positive voltage than under a negative one, whereas it was not sensitive to voltage polarities for the sample with two insulating surfaces. In order to explain experimental results, a simulation model based on continuity equations was established to obtain PD sequences at DC voltage, in which surface charge decay and discharge time lag were taken into account. Simulation results showed that positive surface charges dissipated faster than the negative, and the discharge time lag kept almost unchanged at the same voltage amplitude. The discharge time interval consisted of field recovery time and discharge time lag, and the former was determined by surface charge decay rate. In terms of these, the effect of surface charge decay on discharge frequency was discussed. The research is helpful to clarify PD mechanism at DC voltage. [ABSTRACT FROM AUTHOR]

An efficient and metal‐free double C−H bond amination of N‐aryl enamines using isobutyl nitrite (IBN) has been developed. This method enables the preparation of functionalized quinoxalines in good to excellent yields and tolerates a variety of N‐aryl enamines with diverse functional substituents. Mechanistic studies revealed the presence of a key β‐imino oxime ester intermediate. A quinoxaline derivative could be prepared from β‐carbonyl ester in one‐pot sequence on a gram scale. Finally, two important quinoxaline scaffolds were easily prepared in moderate yields over two steps. [ABSTRACT FROM AUTHOR]

Statistical characteristics of discharge magnitude are significant for insulation diagnosis by monitoring partial discharge (PD) in power apparatuses. However, hitherto, investigations on the PD magnitude distribution in SF6 gas under direct current voltage are insufficient. A current pulse measuring circuit and a ultra‐high‐frequency (UHF) antenna were simultaneously employed to investigate characteristics of positive corona in 0.3 MPa SF6 gas. It is found that compared to the UHF antenna, the common measurement impedance used in laboratories caused several current pulses overlapped, resulting in pulse burst phenomenon. The pulse burst was easily mistaken as a single PD, which actually contained several PDs, thereby negatively affecting obtaining a real discharge magnitude distribution. Moreover, the discharge magnitude distributions were compared when a pulse burst was treated as a single PD and several PDs, respectively. It is found the former and latter one had forms of non‐skewed two‐parameter Weibull distribution with large‐scale parameters and positively skewed two‐parameter Weibull distribution with small‐scale parameters, respectively. Based on this understanding, the change of the distributions with time was investigated, and the results showed that the distribution would have a permanent form of two‐parameter Weibull distribution after a 24‐h transition time. [ABSTRACT FROM AUTHOR]

In order to reveal partial discharge (PD) physical processes at DC voltage, a model with regard to PD taking place within a cavity embedded in polyethylene is established, in which the charge fluid equations and the Poisson equation are employed to simulate streamer propagation and surface charge accumulation processes after it arrives at the gas–solid interface. Meanwhile, parameters such as discharge current and discharge time during a PD sequence are obtained by considering surface charge decay and discharge time lag variation in the discharge time interval. It is found from the simulation results that the electrons generated by the discharge accumulate on the upper surface of the cavity and the time taken to accumulate is less that 1 ns when a positive voltage is applied to the upper electrode. On the contrary, positive ions accumulate on the lower surface, and the time taken is about 90 ns. Besides, the density of positive ions is slightly higher than that of the electrons. During a PD sequence, the decay of surface charges resulting from previous discharge can be considered to be the key factor contributing to the occurrence of subsequent one, and electric field within the cavity mainly depends on negative surface charges just before the subsequent PD takes place, because of the lower decay rate of the negative charges than the positive ones. The discharge time interval can be divided into two parts: discharge time lag and discharge recovery time, which depend on the surface charge decay rate. As surface charge decay rate increases or the discharge time lag decreases, the discharge time interval decreases. Moreover, the discharge current is affected by discharge time lag and the surface charge decay rate. © 2018 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc. [ABSTRACT FROM AUTHOR]

Abstract: The role of a tertiary polymer‐based additive is investigated in increasing the efficiency of inverted low bandgap polymer:fullerene bulk heterojunction (BHJ) solar cells. Charge separation in polymer BHJ solar cells relies on the phase separation between electron accepting fullerene derivatives and photoactive polymers. Proper distribution of individual phases of suitable crystallinities within the active layer is a key factor for efficient charge transport/extraction and high photovoltaic performance. Here, it is demonstrated that the minor addition of a tertiary amorphous polymer, polystyrene (PS), with optimized molecular weights can increase the overall photovoltaic efficiency of poly[N‐9′‐heptadecanyl‐2,7‐carbazole‐alt‐5,5‐(4′,7′‐di‐2‐thienyl‐2′,1′,3′‐benzothiadiazole)]:phenyl‐C61butyric acid methyl ester (PCDTBT:PCBM) inverted BHJ solar cells, through the interfacial‐tension‐driven increase in crystallinities of photoactive phases and redistribution of PCBM molecules away from the top hole‐collecting anode interface. Complementary studies correlating polymer interfacial tension, blend internal structure, charge transport, and photovoltaic characteristics show that tertiary, high molecular‐weight polymers can serve as effective additives for improving the performance of low bandgap polymer solar cells. [ABSTRACT FROM AUTHOR]

Objective: To investigate the gut microbiota in healthy volunteers (HVs), patients with overweight (OW), and patients with obesity (OB), including those with acanthosis nigricans (AN) or without AN (N-AN).Methods: Microbial 16S rRNA genes were examined by using pyrosequencing technology and analyzed by using bioinformatics methods.Results: Subjects in the OW and OB groups showed severe disturbances in glycemic control, lipid profile, and inflammatory markers (all P < 0.05); patients with AN had worse metabolic status (P < 0.001) and a lower diversity of microbiota (P < 0.05). The OB and HV groups showed totally different gut microbiota composition. In the OB group, beneficial microbiotas including Bifidobacterium (0.01% vs. 0.05%, false discovery rate [FDR] = 4.27*10-5 ), anti-inflammatory Faecalibacterium (6.70% vs. 13.82%, FDR = 0.010), and butyrate-producing Ruminococcaceae were significantly decreased, whereas Bacillus (0.58% vs. 0.04%, FDR = 0.013) and potential opportunistic pathogens such as Fusobacterium (1.44% vs. 0.11%, FDR < 0.01) and Escherichia-Shigella (6.01% vs. 0.76%, FDR = 0.041) had outgrown dramatically. Function prediction revealed a significant increase in lipopolysaccharide biosynthesis proteins and bacterial invasion of epithelial cell-associated genes and a significant decrease in glucose and essential amino acid-related genes.Conclusions: Gut microbiotas and their functions were significantly changed in obesity. More prospective studies on association and causality between microbiota and obesity are imperative and might contribute to the prevention, diagnosis, and treatment of obesity. [ABSTRACT FROM AUTHOR]

Recent studies have indicated the clinical significance of tumor-associated macrophages ( TAM) in several malignant tumors including breast cancer. Although recent studies have focused on CD68-positive or CD163-positive TAM in breast cancer, no study has investigated the significance of CD204-positive TAM in breast cancer. We found that CD204 expression on macrophages was evaluated following stimulation with the conditioned medium ( CM) of breast cancer cell lines. Paraffin sections of 149 breast cancer samples which were diagnosed as invasive ductal carcinoma were immunohistochemically analyzed for CD68, CD163 and CD204 expression. The results of analyses indicated that a high number of CD204-positive TAM was associated with worse clinical prognoses, including relapse-free survival, distant relapse-free survival and breast cancer-specific survival; however, neither the numbers of CD68-positive or CD163-positive TAM were associated with clinical courses. Of the clinicopathological factors investigated, estrogen receptor, Ki-67 index, hormone subtype, and histological grade were significantly related to the increased number of CD163-positive and CD204-positive TAM. These data indicate the clinical significance of CD204-positive TAM in breast cancer progression and CD204 is a marker for predicting clinical prognosis in breast cancer. [ABSTRACT FROM AUTHOR]

Immune escape and tolerance in the tumor microenvironment are closely involved in tumor progression, and are caused by T-cell exhaustion and mediated by the inhibitory signaling of immune checkpoint molecules including programmed death-1 ( PD-1), cytotoxic T-lymphocyte associated protein 4, and T-cell immunoglobulin and mucin domaincontaining molecule-3. In the present study, we investigated the expression of the PD-1 ligand 1 ( PD-L1) in a lymphoma microenvironment using paraffin-embedded tissue samples, and subsequently studied the detailed mechanism of upregulation of PD-L1 on macrophages using cultured human macrophages and lymphoma cell lines. We found that macrophages in lymphoma tissues of almost all cases of adult T-cell leukemia/lymphoma ( ATLL), follicular lymphoma and diffuse large B-cell lymphoma expressed PD-L1. Cell culture studies showed that the conditioned medium of ATL-T and SLVL cell lines induced increased expression of PD-L1/2 on macrophages, and that this PD-L1/2 overexpression was dependent on activation of signal transducer and activator of transcription 3 (Stat3). In vitro studies including cytokine array analysis showed that IL-27 (heterodimer of p28 and EBI3) induced overexpression of PD-L1/2 on macrophages via Stat3 activation. Because lymphoma cell lines produced IL-27B ( EBI3) but not IL-27p28, it was proposed that the IL-27p28 derived from macrophages and the IL-27B ( EBI3) derived from lymphoma cells formed an IL-27 (heterodimer) that induced PD-L1/2 overexpression. Although the significance of PD-L1/2 expressions on macrophages in lymphoma progression has never been clarified, an IL-27-Stat3 axis might be a target for immunotherapy for lymphoma patients. [ABSTRACT FROM AUTHOR]

A novel and non-cytotoxic self-healing supramolecular elastomer (SE) is synthesized with small-molecular biological acids by hydrogen-bonding interactions. The synthesized SEs behave as rubber at room temperature without additional plasticizers or crosslinkers, which is attributed to the phase-separated structure. The SE material exhibits outstanding self-healing capability at room temperature and essential non-cytotoxicity, which makes it a potential candidate for biomedical applications. [ABSTRACT FROM AUTHOR]

An unsymmetrically protonated PN3-pincer complex in which ruthenium is coordinated by one nitrogen and two phosphorus atoms was employed for the selective generation of hydrogen from formic acid. Mechanistic studies suggest that the imine arm participates in the formic acid activation/deprotonation step. A long life time of 150 h with a turnover number over 1 million was achieved. [ABSTRACT FROM AUTHOR]

Background & Aims Occult hepatitis B virus infection ( OBI) in patients undergoing liver transplantation ( LT) is a suspected source of de novo hepatitis B virus ( HBV) infection after LT. This study aimed to investigate the prevalence of OBI in liver transplant recipients with alcoholic cirrhosis and demonstrate the association between OBI and de novo HBV infection after LT in these patients. Methods Forty-three patients with alcoholic cirrhosis who were negative for HBsAg before LT were recruited in this retrospective study. DNA was extracted from paraffin-embedded native liver tissues and quantified for HBV DNA by real-time PCR. Correlation between de novo HBV infection after LT (positive HBsAg and/or detectable HBV DNA in serum) and detection of intrahepatic HBV DNA before LT was analysed. Results Detectable HBV DNA in the explanted liver was found in 41.9% (18/43) of the patients and was thus defined as OBI, which was correlated with the presence of serum hepatitis B core antibody ( P = 0.008). De novo HBV infection occurred in 18.6% (8/43) of the recipients at a median of 10 months after LT. The rate of de novo HBV infection was 38.9% (7/18) in patients with OBI, compared with 4% (1/25) in patients without OBI ( P = 0.004). Furthermore, de novo HBV infection was inversely correlated with the presence of hepatitis B surface antibody in recipients with OBI ( P = 0.026). Conclusion With a prevalence of 41.9% in liver transplant recipients with alcoholic cirrhosis, OBI in the native liver can predict de novo HBV infection after LT. [ABSTRACT FROM AUTHOR]

Aortic pulse wave velocity (a PWV) is elevated in patients with chronic kidney disease (CKD) and predicts cardiovascular risk. However, the natural progression of arterial stiffness in these patients remains uncertain. Therefore, the main aim of this study was to investigate the development of a PWV and to identify potential factors associated with its progression. a PWV measurement was carried out in 70 CKD patients at baseline and after 12 months. Correlations to several variables, in particular annual glomerular filtration rate reduction and diabetes mellitus, were studied. In the cohort, a PWV significantly increased in 1 year by 1.1 m/s ( P<.01). Dividing the group into patients with stable and progressive a PWV, factors associated with accelerated progression were age, systolic blood pressure, and diabetes, whereas loss of renal function had no significant impact. The annual a PWV progression in CKD patients reached 1 m/s, which predicts an increased cardiovascular risk. Variables involved with progressive arterial stiffness need further evaluation. [ABSTRACT FROM AUTHOR]

The purpose of this study was to develop a new formulation of intravenous lipid microspheres for bufadienolides (bufadienolides-loaded lipid microspheres, BU-LM) and investigate the stability of BU-LM after dilution and long-term storage. Photon correlation spectroscopy, electrophoretic light scattering, and light microscopy were used to evaluate the physical characteristics of BU-LM. The chemical properties of bufadienolides were measured by high-performance liquid chromatography. The optimum BU-LM, consisting of 10% MCT, 3.0% Lipoid S75, 0.4% F68, 0.05% sodium oleate and 2.5% glycerol, was prepared by emulsification with a high-speed shear mixing at 10 000 rpm for 12 min and a high-pressure homogenization at 800 bar for 8 cycles at 30°C. The BU-LM at pH 6.48, with the particle size distribution of 175.2 ± 57.3 nm, ζ-potential of −32.10 mV, entrapment efficiency of 86.9%, 91.7%, 92.9%, and contents of 20.8%, 31.3%, 50.4% for B, C, R, respectively, was stable after sterilization in a 121°C rotating autoclave water steam bath for 10 min. Moreover, BU-LM had sufficient physicochemical stability after dilution with 5% glucose injection and long-term storage at 4 ± 2°C for 18 months. BU-LM has a great potential for clinical applications as a new drug delivery system for bufadienolides. Practical applications: Bufadienolides, mainly composed of bufalin (B), cinobufagin (C), and resibufogenin (R) have poor aqueous solubility and are chemically unstable. Currently the main marketable products of bufadienolides are solution injections, which cause serious venous irritation and in this formulation, the drug is not protected from degradation. Lipid microspheres, with the unique properties of a low cost, low toxicity, good storage stability, easy to scale up production, sustained release and targeting effect, incorporate the drugs into the interior oil phase and the oil-water interfacial film; thus a direct contact of the drug with body fluids and tissues is prevented, which increases the stability of the drugs and minimizes the possible side effects. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study is to identify the titres of protective hepatitis B surface antibodies (anti-HBs) in the blood and their effective factors in the early stage after liver transplantation (LT) for hepatitis B virus (HBV) related diseases. The condition of anti-HBs lost in ascites fluid was also investigated. Methods: Twenty-six patients who received LT were administered prophylaxis of lamivudine combining intravenous hepatitis B immunoglobulin (HBIG) post-LT. The titres of anti-HBs were recorded and analyzed daily in blood and ascites fluid within the first week post-LT. Results: In the first 5 days post-LT, the titres of anti-HBs in HBV DNA positive groups, high hepatitis B surface antigen (HBsAg) groups, hepatitis B e antigen (HBeAg) positive groups were lower than that in the parallel HBV DNA negative groups, low HBsAg groups and HBeAg negative groups. The mean titre level of anti-HBs in ascites fluid is 224.89 IU/L and fluctuated from 0.00 IU/L to 968.50 IU/L, which is also correlated with anti-HBs titres in blood drawn at the same time ( r = 0.927, P = 0.000). The level of anit-HBs in ascites fluid was very high; however, it fluctuated in a wide range (from 0.00 IU to 908.55 IU). Conclusions: Patients in high risk groups should receive a higher level of HBIG to maintain sufficient amounts of anti-HBs in the early stage post-LT, while the patients in low risk groups need a lower level of HBIG administration. Furthermore, the lost amount of anti-HBs in ascitic fluid post-LT has minimum impact on the anti-HBs titres in blood. [ABSTRACT FROM AUTHOR]

Coenzyme Q10 (CoQ10) is a naturally occurring compound located in all membranes throughout the cell. A rapid and sensitive HPLC method was developed to determine the concentration of CoQ10 in dog plasma using a surrogate matrix. Chromatographic separation was carried out on a Diamonsil C18 column with the UV detector set at 275 nm. Methanol-2-propanol (40:60, v/v) was used as a mobile phase delivered at a flow rate of 1.0 mL/min. Calibrators were prepared using blank plasma-K2HPO4 buffer (50 m m, pH 8.0)-saline (1:3:6, v/v/v) as surrogate matrix. It was shown that the surrogate matrix had similar properties to dog plasma for CoQ10 in extraction, freeze-thaw and stability. The assay was linear over the concentration range of 0.10-100 µg/mL. The intra- and inter-day precisions were within 13.3% in terms of relative standard deviation (RSD%) and the accuracy was within ±7.5% in terms of relative error. This simple and reproducible HPLC method with less plasma volume (0.4 mL) and adequate sensitivity was successfully applied to pharmacokinetic studies of CoQ10 in dogs and an investigation of the effect of CoQ10 formulation on CoQ10 baseline levels. Copyright © 2010 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The degradation kinetics in vitro and pharmacokinetics of bufadienolides loaded in lipid microsphere (BU-LM) after intravenous (IV) administration were investigated and compared with bufadienolides solution (BU-S). The bioavailabilities of BU-LM after intraportal ( FIP), intraduodenal ( FID), and intragastric ( FIG) administrations to rats were also evaluated. The degradation kinetics showed that BU-LM could protect bufadienolides from rapid metabolism in the plasma and gastrointestinal tract. The pharmacokinetic study revealed that BU-LM after IV administration exhibited longer half-life, longer mean residence time and higher apparent volume of distribution than intravenous BU-S. After different routes of administration of BU-LM, cinobufagin (C), and resibufogenin (R) were metabolized completely and could not be detected at an oral dose of 6 mg/kg. Furthermore, C exhibited a complete hepatic first-pass effect after IP administration of 0.5 mg/kg BU-LM. Bufalin (B), the lowest component of the BU-LM could be detected at any administration and the FIG, FID, and FIP for B were 43.05, 88.93, and 93.31%, respectively. R had a FID and FIP of only 1.51 and 2.77%, respectively. The results demonstrated that the stomach appeared to be the dominating site of metabolism for B and the liver for C and R. Practical applications: Bufadienolides, consisting of bufalin (B), binobufagin (C), and resibufogenin (R) are easily hydrolyzed (catalyzed by acids, bases, and enzymes) and are metabolized rapidly in rats because of their chemical structures, especially C. However, the three bufadienolides could be protected from degradation effectively and the degradation half-lives could be extended to different degrees by using lipid microspheres (LM) as a delivery system. Also, after intravenous administration to rats, bufadienolides-loaded lipid microspheres (BU-LM) could slow down the metabolism and elimination of bufadienolides, delay the release and increase the targeted effect of the drug compared with bufadienolides aqueous solution (BU-Siv). Consequently, LM is a promising alternative vehicle for bufadienolides. [ABSTRACT FROM AUTHOR]

Pan CR, Schmaderer C, Roos M, von Eynatten M, Sollinger D, Lutz J, Heemann U, Baumann M. Comparing aortic stiffness in kidney transplant recipients, hemodialysis patients, and patients with chronic renal failure. Clin Transplant 2011: 25: E463-E468. © 2011 John Wiley & Sons A/S. Abstract: Background: The poor cardiovascular survival of patients with renal insufficiency is improved by transplantation. Carotid-femoral pulse wave velocity (PWV) is able to predict independently overall and cardiovascular mortality. PWV is elevated in renal insufficiency. Consequently, PWV may change according to the improvement in renal function after kidney transplantation. Methods: In a cross-sectional setting, PWV was determined in 40 renal transplant recipients (RTx) and compared to the PWV of 40 age- and gender-matched patients with comparable renal insufficiency (CKD) and 40 age- and gender-matched hemodialysis patients (HD). Results: RTx and CKD patients had comparable eGFR (RTx: 42.9 ± 18.4, CKD: 48.3 ± 29.1 mL/min/1.73 m2) and protein/creatinine ratio (RTx: median 172.5, 25th percentile 97.75, 75th percentile 344.5, CKD: median 183.272, 25th percentile 100.00, 75th percentile 470.00 mg/g creatinine). There was no significant difference in PWV between RTx 3-12 months post-transplant and CKD or HD patients (RTx: 9.65 ± 1.57, CKD: 9.98 ± 3.91, HD: 10.27 ± 2.89 m/s; n = 20 pairs). Similarly, PWV in transplant patients >12-month post-transplant was similar to that of CKD and HD patients (RTx: 9.71 ± 2.23, CKD: 9.36 ± 2.74, HD: 9.84 ± 3.41 m/s; n = 20 pairs). Discussion: We could not detect significant differences in PWV comparing RTx with age- and gender-matched CKD patients. [ABSTRACT FROM AUTHOR]

Factors affecting the student use of a course management system in a web-enhanced course are investigated using the technology acceptance model. Represented in the present study is the second phase of the analysis, with a focus on the causal relationship of subjective norms to student attitudes towards WebCT and their effect on three dependent variables: (1) end-of-course grades; (2) online frequency; and (3) future preference to take a web-enhanced class over a face-to-face course. Structural equation modelling was used to analyse the measures of the two independent variables across three time periods. Findings suggest that the proposed model fits the data well and that it is useful to model student attitudes and perceived social pressure to understand certain student outcomes. Further recommendations for researchers and practitioners are addressed. [ABSTRACT FROM AUTHOR]