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Background and Purpose: Although our previous data indicated that claudin 18 isoform 2 (CLDN18.2)‐targeted chimeric antigen receptor (CAR) T cells displayed remarkable clinical efficacy in CLDN18.2‐positive gastric cancer, their efficacy is limited in pancreatic ductal adenocarcinoma (PDAC). The tumour microenvironment (TME) is one of the main obstacles to the efficacy of CAR‐T and remodelling the TME may be a possible way to overcome this obstacle. The TME of PDAC is characterized by abundant cancer‐related fibroblasts (CAFs), which hinder the infiltration and function of CLDN18.2‐targeted CAR‐T cells. The expression of fibroblast activation protein alpha (FAP) is an important feature of active CAFs, providing potential targets for eliminating CAFs. Experimental Approach: In this study, we generated 10 FAP/CLDN 18.2 dual‐targeted CAR‐T cells and evaluated their anti‐tumour ability in vitro and in vivo. Key Results: Compared with conventional CAR‐T cells, some dual‐targeted CAR‐T cells showed improved therapeutic effects in mouse pancreatic cancers. Further, dual‐targeted CAR‐T cells with better anti‐tumour effect could suppress the recruitment of myeloid‐derived suppressor cells (MDSCs) to improve the immunosuppressive TME, which contributes to the survival of CD8+ T cells. Moreover, dual‐targeted CAR‐T cells reduced the exhaustion of T cells in transforming TGF‐β dependent manner. Conclusion and Implications: The dual‐targeted CAR‐T cells obtained enhancement of T effector function, inhibition of T cell exhaustion, and improvement of tumour microenvironment. Our findings provide a theoretical rationale for dual‐targeted FAP/CLDN 18.2 CAR‐T cells therapy in PDAC. [ABSTRACT FROM AUTHOR]

A high precision estimation algorithm for ground moving targets in multi‐channel wide‐area surveillance ground moving target indication systems is proposed based on maximum likelihood method. The main concept of this novel algorithm is to estimate the azimuth angle of the detected targets using maximum likelihood method with the space steering vector formed by the estimated interferometric phase extracted from the mainlobe clutter region of the real data. Through this novel algorithm, the effect of channel errors among the multi‐channels can be well reduced. Simulation experiments demonstrate the effectiveness of the proposed algorithm. [ABSTRACT FROM AUTHOR]

Objective: In this study, we employed a Mendelian randomization (MR) approach to investigate the independent causal associations of six body composition traits with gestational diabetes mellitus (GDM). Methods: Genome-wide significant levels (P < 10 9 5-8) of single nucleotide polymorphisms associated with body water mass, total protein, whole body fat-free mass, weight, whole body fat mass, and body fat percentage were used as instrumental variables. Data on GDM were obtained from the FinnGen Consortium, and both univariable and multivariable Mendelian randomization were performed. We utilized five different analytical methods including inverse-variance weighted (IVW), MR Egger, weighted median, simple mode, and weighted mode to assess the robustness of the results. Results: With univariable Mendelian randomization, the risk of GDM increased per 1-standard deviation (SD) increase in weight (ORweight = 1.297, P = 3.06 9 10-5), whole body fat mass (ORwhole body fat mass = 1.408, P = 1.32 9 10-6), and the risk of GDM increased per percent increase in body fat percentage (ORbody fat percentage = 1.661, P = 1.01 9 10-8). Total protein had a protective effect on the risk of GDM (ORtotal protein = 0.880, P = 0.048). However, there was no significant causal association between increases in body water mass and whole body fat-free mass per SD and the risk of GDM. Causal associations between weight, whole body fat mass, body fat percentage, and total protein with GDM were reduced to null in multivariable Mendelian randomization. Conclusion: The present study furnishes genetic evidence to elucidate the causal relationship between body composition traits and GDM. Additionally, further studies are imperative to establish a causal connection between body composition traits and gestational diabetes mellitus. [ABSTRACT FROM AUTHOR]

In light of the engineering characteristics of fine-grained tailings, such as their high moisture content, high compressibility, difficult deposition, and difficult consolidation, and based on the summary and analysis of the experience of tailing dam construction in China and abroad, a new comprehensive treatment technology suitable for dam construction on a weak beach, which is composed of strengthening foundation with the soilbag, subdam stabilization, and collaborative drainage, is proposed. Taking a dam construction project on the weak beach of a tailing pond in China as the research object and through the study of the reinforcement mechanism of the soft beach treated using the soilbag method, it can be seen that the soilbag body has the mechanism of strength growth by sand fixation and water permeability and constraint formation and can achieve an overall stable effect of extrusion and silt replacement, stacking and surcharge, and flexible embedding in a weak beach. Using this method, combined with relevant monitoring technology, a good demonstration of dam construction speed of up to 30 m/a and a safe dam construction height of up to 60 m on a weak beach surface is achieved in a tailing dam construction project, which provides a good reference for the design and construction of fine tailing dam engineering and the cooperative disposal of adverse geological conditions. [ABSTRACT FROM AUTHOR]

Introduction: Coronary artery calcification and cardiac abnormalities are common in hemodialysis patients. The value of lanthanum carbonate over calcium‐based phosphate binders in managing the progression of coronary artery calcification is debated. We reviewed all randomized controlled trials (RCTs) comparing the two strategies in these patients. Methods: RCTs comparing lanthanum carbonate with calcium‐based phosphate binders used in adult hemodialysis patients were identified in the PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, China Science and Technology Journal, and Wanfang databases. Findings Ten RCTs involving 687 patients were suitable for inclusion. Compared with calcium‐based phosphate binders, lanthanum carbonate yielded lower coronary artery calcium scores (weighted mean difference, WMD: −74.28, 95% CI: −149.89, 1.33), change in coronary artery calcium scores (WMD: −105.18, 95% CI: −113.83, −96.53), and left ventricular mass index (WMD: −29.95, 95% CI: −54.25, −7.45). Lanthanum carbonate was significantly associated with lower levels of serum phosphate (WMD: −0.18, 95% CI: −0.26, −0.10), calcium (WMD: −0.22, 95% CI: −0.25, −0.20), and fibroblast growth factor 23 (FGF23) (standard mean difference: −3.78, 95% CI: −5.60, −1.96) but not intact parathyroid hormone (WMD: −4.23, 95% CI: −64.12, 55.65). Moreover, a reduced risk of nonfatal cardiovascular events (OR: 0.31, 95% CI: 0.10–0.97) but not all‐cause mortality (OR: 1.08, 95% CI: 0.39–3.01) in lanthanum carbonate therapy was observed. Discussion In hemodialysis patients, lanthanum carbonate therapy may impede the progression of coronary artery calcification and left ventricular mass index and lead to reduced serum phosphate, calcium, FGF23, and nonfatal cardiovascular events compared with calcium‐based phosphate binders. However, more well‐designed RCTs are required for confirmation. [ABSTRACT FROM AUTHOR]

(A) Decreasingtrend of serumLPC (18:0)level in pneumonia patients with T2DM in relation to non-diabetic pneumonia patients. The Student-Newman-Keuls q results showed that the serum 6of8 LETTERTOEDITOR FIGURE 4 The serum LPC (18:0) level for discriminating non-diabetic pneumonia patients and pneumonia patients with T2DM. Thirty-six pneumonia patients with T2DM, 31 nondiabetic pneumonia patients, 31 T2DM patients without pneumonia,and31healthycontrolswithoutpneumoniaor T2DMwereenrolledbetweenMarch2018andDecember 2018inthediscoveryset. [Extracted from the article]

This study presents a unified current-source power quality conditioner of inherent no circulating current. It is formed of a three-leg current-source ac/ac converter and a specially designed small size dc-link. Owing to the transformers-less feature and small size dc-link, the proposed topology has the benefit of high power density. In addition, without the need to address the circulating current issue, it is easier to design the controllers and filters for the circulating current compared to other existing transformer-less unified power quality conditioners. To handle the harmonic currents compensation, voltage sags/swells elimination, power factor correction simultaneously and achieve excellent dynamic and steady-state performance, a direct control method based on an extended repetitive disturbance observer is proposed. Detailed analysis of topology and operation principles is given, followed by the modulation scheme and the developed control method. Simulations and experimental results are presented to verify the effectiveness of the conditioner. [ABSTRACT FROM AUTHOR]

Stylo [Stylosanthes guianensis (Aublet) Sw.] is an important forage legume and cover crop in tropical and southern subtropical regions. Its growth and survival are largely affected by low temperature in winter in subtropical regions. It is important to improve its chilling tolerance. S-adenosylmethionine synthetase (SAMS) is the key enzyme catalyzing the formation of S-adenosylmethionine (SAM), a precursor of polyamines synthesis. To improve chilling tolerance in stylo, MfSAMS1 from Medicago falcata was overexpressed in stylo plants. DNA gel blot hybridization and quantitative reverse transcription PCR analysis showed that MfSAMS1 was inserted into the genomes of transgenic plants and expressed. Compared to the wild-type, transgenic plants had enhanced SAM and spermidine levels and increased chilling tolerance with higher level of the maximum photochemical efficiency of photosystem II (Fv/Fm) and lower ion leakage after chilling treatment. Polyamine oxidase activity and H2O2 levels were increased in transgenic plants compared with the wild-type. In addition, higher activities of superoxide dismutase and catalase were observed in transgenic plants than in the wild-type. The results suggest that overexpression of MfSAMS1 promoted polyamine synthesis and oxidation, which in turn improved H2O2-induced antioxidant protection and protected transgenic plants against chilling stress. [ABSTRACT FROM AUTHOR]

A transformer-less dynamic voltage restorer (DVR) with bipolar voltage gain capability is proposed in this study. The DVR is formed by a three-leg ac/ac converter with its output capacitor in series with the transmission line. Since the energy used for voltage compensation is obtained from the grid, long-time voltage disturbances can be compensated without using bulky energy storage elements. As a result, the proposed DVR has the features of compact structure, light weight, and low cost. Moreover, it also has a high reliability as the commutation problem is avoided by adopting the proposed modulation strategy. A detailed analysis of the topology structure and operation principle is given, followed by the developed control method. Finally, simulations and experimental results are presented to verify the validity of the DVR. [ABSTRACT FROM AUTHOR]

The functional role of respiratory microbiota has attracted an accumulating attention recently. However, the role of respiratory microbiome in lung carcinogenesis is mostly unknown. Our study aimed to characterize and compare bilateral lower airway microbiome of lung cancer patients with unilateral lobar masses and control subjects. Protected bronchial specimen brushing samples were collected from 24 lung cancer patients with unilateral lobar masses (paired samples from cancerous site and the contralateral noncancerous site) and 18 healthy controls undergoing bronchoscopies and further analyzed by 16S rRNA amplicon sequencing. As results, significant decreases in microbial diversity were observed in patients with lung cancer in comparison to the controls, alpha diversity steadily declined from healthy site to noncancerous to cancerous site. Genus Streptococcus was significantly more abundant in cancer cases than the controls, while Staphylococcus was more abundant in the controls. The area under the curve of genus Streptococcus used to predict lung cancer was 0.693 (sensitivity = 87.5%, specificity = 55.6%). The abundance of genus Streptococcus and Neisseria displayed an increasing trend whereas Staphylococcus and Dialister gradually declined from healthy to noncancerous to cancerous site. Collectively, lung cancer-associated microbiota profile is distinct from that found in healthy controls, and the altered cancer-associated microbiota is not restricted to tumor tissue. The genus Streptococcus was abundant in lung cancer patients and exhibited moderate classification potential. The gradual microbiota profile shift from healthy site to noncancerous to paired cancerous site suggested a change of the microenvironment associated with the development of lung cancer. [ABSTRACT FROM AUTHOR]

The size of particles is a principal parameter to design drug delivery vehicles. In this work, albumin nanoparticles were fabricated from microscaled poly[lactic-co-(glycolic acid)] (PLGA) templates using layer-by-layer (LbL) assembly, which are different from traditional LbL-based hollow capsules. The albumin nanoparticles exhibit a spherical shape and solid inner structure. The formation mechanism of these albumin nanoparticles was proposed based on PLGA templates, mechanical property of albumin and external sonication. [ABSTRACT FROM AUTHOR]

The first step of nitrogen assimilation in higher plants, the energy-driven incorporation of ammonia into glutamate, is catalyzed by glutamine synthetase. This central process yields the readily metabolizable glutamine, which in turn is at the basis of all subsequent biosynthesis of nitrogenous compounds. The essential role performed by glutamine synthetase makes it a prime target for herbicidal compounds, but also a suitable intervention point for the improvement of crop yields. Although the majority of crop plants are dicotyledonous, little is known about the structural organization of glutamine synthetase in these organisms and about the functional differences between the different isoforms. Here, the structural characterization of two glutamine synthetase isoforms from the model legume Medicago truncatula is reported: the crystallographic structure of cytoplasmic GSII-1a and an electron cryomicroscopy reconstruction of plastid-located GSII-2a. Together, these structural models unveil a decameric organization of dicotyledonous glutamine synthetase, with two pentameric rings weakly connected by inter-ring loops. Moreover, rearrangement of these dynamic loops changes the relative orientation of the rings, suggesting a zipper-like mechanism for their assembly into a decameric enzyme. Finally, the atomic structure of M. truncatula GSII-1a provides important insights into the structural determinants of herbicide resistance in this family of enzymes, opening new avenues for the development of herbicide-resistant plants. [ABSTRACT FROM AUTHOR]

The present study investigates some novel categorical properties of soft sets. By combining categorical theory with soft set theory, a categorical framework of soft set theory is established. It is proved that the category SFun of soft sets and soft functions has equalizers, finite products, pullbacks, and exponential properties. It is worth mentioning that we find that SFun is both a topological construct andCartesian closed.The category SRel of soft sets and??-soft set relations is also characterized, which shows the existence of the zero objects, biproducts, additive identities, injective objects, projective objects, injective hulls, and projective covers. Finally, by constructing proper adjoint situations, some intrinsic connections between SFun and SRel are established. [ABSTRACT FROM AUTHOR]

This paper is concerned with the consensus problem of general linear discrete-timemultiagent systems (MASs)with randompacket dropout that happens during information exchange between agents. The packet dropout phenomenon is characterized as being a Bernoulli random process. A distributed consensus protocol with weighted graph is proposed to address the packet dropout phenomenon. Through introducing a new disagreement vector, a new framework is established to solve the consensus problem. Based on the control theory, the perturbation argument, and the matrix theory, the necessary and sufficient condition for MASs to reach mean-square consensus is derived in terms of stability of an array of low-dimensional matrices. Moreover, mean-square consensusable conditions with regard to network topology and agent dynamic structure are also provided. Finally, the effectiveness of the theoretical results is demonstrated through an illustrative example. [ABSTRACT FROM AUTHOR]

Satisfiability Modulo Theories (SMT) techniques are widely used nowadays. SMTsolvers are typically used as verification backends. When an SMT solver is invoked, it is quite important to ensure the correctness of its results. To address this problem, we propose a unified certificate framework based on DPLL(T), including a uniformcertificate format, a unified certificate generation procedure, and a unified certificate checking procedure. The certificate format is shown to be simple, clean, and extensible to different background theories. The certificate generation procedure is well adapted to most DPLL(T)-based SMT solvers. The soundness and completeness for DPLL(T) + certificates were established. The certificate checking procedure is straightforward and efficient. Experimental results show that the overhead for certificates generation is only 10%, which outperforms other methods, and the certificate checking procedure is quite time saving. [ABSTRACT FROM AUTHOR]

Thereliability of discrete element method (DEM) numerical simulations is significantly dependent on the particle-scale parameters and boundary conditions. To verify the DEM models, two series of biaxial compression tests on ellipse-shaped steel rods are used. The comparisons on the stress-strain relationship, strength, and deformation pattern of experiments and simulations indicate that the DEM models are able to capture the key macro- and micromechanical behavior of inherently anisotropic granular materials with high fidelity. By using the validated DEM models, the boundary effects on the macrodeformation, strain localization, and nonuniformity of stress distribution inside the specimens are investigated using two rigid boundaries and one flexible boundary. Theresults demonstrate that the boundary condition plays a significant role on the stress-strain relationship and strength of granular materials with inherent fabric anisotropy if the stresses are calculated by the force applied on the wall. However, the responses of the particle assembly measured inside the specimens are almost the same with little influence from the boundary conditions. The peak friction angle obtained from the compression tests with flexible boundary represents the real friction angle of particle assembly. Due to the weak lateral constraints, the degree of stress nonuniformity under flexible boundary is higher than that under rigid boundary [ABSTRACT FROM AUTHOR]

Maternal iron status is thought to be related to postpartum depressive symptoms. The purpose of the present study was to evaluate the relationship between pre- and postnatal maternal iron status and depressive symptoms in pilot (n = 137) and confirmatory (n = 567) samples of Chinese women. Iron status was evaluated at mid- and late pregnancy and 3 days postpartum. The Edinburgh Postnatal Depression Scale (EPDS) was used to assess maternal postpartum depression 24-48 hours after delivery and 6 weeks later. In the pilot sample, correlations between early- and late-pregnancy maternal Hb and EPDS scores at 6 weeks were r = 0.07 and -0.01, respectively (nonsignificant). In the confirmatory sample, the correlations between maternal iron measures (Hb, MCV, ZPP, ferritin, sTfR, and sTfR Index) in mid- or late pregnancy or 3 days postpartum and EPDS scores shortly after delivery or at 6 weeks were also low (r values < 0.10). EPDS scores in anemic and nonanemic mothers did not differ, regardless of sample or timing of maternal iron status assessment. In addition, women with or without possible PPD were similar in iron status in both samples. Thus, there was no relationship between maternal iron status and postpartum depression in these samples. [ABSTRACT FROM AUTHOR]

Enzymatic digestion, the commonly used method of adipose-derived stromal cells isolation, is time consuming and expensive, especially when applied to large volumes of tissue. In the present study, the characteristics of the cells obtained by adipose tissue explant culture were studied. We found that adipose tissue fragments could adhere onto the growth surface of flasks in a very short time after plating and that fibroblast-like cells migrated from the explants and reached confluence. Morphologic analysis and surface markers expression suggested the mesenchymal origin of the cells derived from adipose tissue explants. After in vitro expansion these cells were successfully induced into adipogenic, osteogenic, and chondrogenic lineages, which demonstrated their multipotency. The high growth rate and colony-forming efficiency of explant-derived cells were similar to those of cells obtained by digestion. Furthermore, explant culture gave higher yield of cells than digestion method after primary culture. The experiment of ectopic adipogenesis in nude mice suggested the prospects for tissue engineering of these cells. In conclusion, we obtained multipotent stromal cells from adipose tissue by explant culture, and this method was simple, time saving, and gave a high yield of cells. Therefore, explant culture can be used as an effective way to isolate adipose-derived stromal cells for tissue engineering. [ABSTRACT FROM AUTHOR]

ARu(bpy)32+-based electrochemiluminescence (ECL) detection coupled with capillary electrophoresis (CE) was developed for the determination of atropine sulfate on the basis of an Eu-PB modified platinum electrode as the working electrode. The analyte was injected to separation capillary of 50 cm length (25 μm i.d., 360 μm o.d.) by electrokinetic injection for 10 s at 10 kV. Parameters related to the separation and detection were discussed and optimized. It was proved that 10mM phosphate buffer at pH 8.0 could achieve the most favorable resolution, and the high sensitivity of detection was obtained by using the detection potential at 1.15 V and 5mM Ru(bpy)32+ in 80mM phosphate buffer at pH 8.0 in the detection reservoir. Under the optimized conditions, the ECL peak area was in proportion to atropine sulfate concentration in the range from 0.08 to 20 μg · mL-1 with a detection limit of 50 ng · mL-1 (3s). The relative standard derivations of migration time and peak area were 0.81 and 3.19%, respectively. The developed method was successfully applied to determine the levels of atropine sulfate in urine samples of patients with recoveries between 90.9 and 98.6%. [ABSTRACT FROM AUTHOR]

We analyzed the causes of death among active leprosy patients in China, to better understand the disease and improve the quality of services, by performing a retrospective study involving 24 provinces of China. Information about patients with active leprosy who were not clinically cured and died between January 1, 2000, and December 31, 2005, was collected by professionals at county levels. A total of 524 deaths were analyzed. The leading cause of death was suicide. There were 86 patients (16%) who died at a mean of 21 ± 19 months after starting multi-drug therapy (MDT). The second and third leading causes of death were cardiovascular disease and organ failure associated with advanced age, respectively. Two hundred and twenty-one patients (42%) died within one year of beginning MDT. The second month of MDT was the riskiest for newly treated patients; approximately 20% of patients succumbed to liver failure, 33% to dapsone (diaminodiphenylsulfone/DDS) allergy, and 27% to renal insufficiency during this period. Among 143 deaths related to leprosy, 37 (26%) occurred within three months of starting MDT. We recommend that newly diagnosed patients should be provided with no more than two months of MDT blister packs. [ABSTRACT FROM AUTHOR]

The human coronaviruses (HCoVs) HCoV-NL63 and HCoV-HKU1 are two recently discovered coronaviruses that circulate widely and are associated with acute respiratory infections (ARI). We detected HCoV-NL63 and HCoV-HKU1 in specimens collected from May 2008 to March 2010 from patients with ARI aged <7.75 years of age attending the Beijing Children's Hospital. Thirty-two (8.4%) and 57 (14.9%) of 382 specimens tested positive for HCoV-NL63 and HCoV-HKU1, respectively, by real-time RT-PCR. Use of a Luminex xTAG RVP Fast kit showed that coinfection with respiratory syncytial virus and parainfluenza 3 virus was common among patients infected with either virus type. InHCoV-HKU1-infected patients, the predominant clinical symptoms were cough, fever, and expectoration. In HCoV-NL63-infected patients they were cough, fever, and rhinorrhea. Phylogenetic studies showed that the HCoV-HKU1 nucleoprotein gene was relatively conserved compared to NCBI reference sequences, while the 1ab gene of HCoV-NL63 showed more variation. [ABSTRACT FROM AUTHOR]

Drug resistance is the major obstacle to successful cancer treatment. To understand the mechanisms responsible for drug resistance in tongue cancer, Tca8113 cells derived from moderately differentiated human tongue squamous cell carcinoma were exposed to stepwise escalated concentrations of pingyangmycin (PYM) to develop the resistant cell line called Tca8113/PYM, which showed over 18.78-fold increased resistance to PYM as compared with Tca8113 cells, and cross-resistance to cisplatin, pirarubicin, paclitaxel, adriamycin, and mitomycin. We found that the resistance was not associated with multidrug resistance transporter 1 (p170, p-gp), multidrug resistance-associated protein 1 and breast cancer resistance protein overexpression, so we hypothesized that Tca8113/PYM cells must have some other resistance mechanism selected by PYM. To test this hypothesis, the global gene expression profiles between Tca8113 and Tca8113/PYM cells were compared by cDNA microarray. Eighty-nine genes and thirteen expressed sequence tags with differential expression levels between the two cell lines were identified. Some differential expression levels were validated with real-time PCR and western blot. Furthermore, the functional validation showed that both carbonic anhydrase (CA) inhibitor acetazolamide application and CA9 silencing with CA9 antisense oligonucleotides contribute to the medium pH increase of Tca8113/PYM cells and enhanced PYM chemosensitivity. Moreover, both acetazolamide and CA9 antisense oligonucleotides significantly increased PYM-induced caspase 3 activation in Tca8113/PYM cells. Thus, our study suggests that the resistance of Tca8113/PYM cells is probably associated with CA9 and other differential expression molecules, and that CA9 may be an important marker for prediction of PYM responsiveness in tongue cancer chemotherapy. [ABSTRACT FROM AUTHOR]

Accumulation of advanced oxidation protein products (AOPPs) is prevalent in metabolic syndromes, a condition with impaired preadipocytes differentiation. In the present study, we tested the hypothesis that AOPPs disturb preadipocyte differentiation. Exposure of 3T3-L1 preadipocytes to increased levels of AOPPs inhibited accumulation of intracellular triglyceride and decreased the expression of the essential markers of matured adipocytes, such as adipocyte fatty-acid-binding protein (aP2), CAAT/enhancer-binding protein (C/EBP)-α, and peroxisome proliferator-activated receptor (PPAR)-γ, in response to standard adipogenic induction. Inhibitory effects of AOPPs on preadipocytes differentiation was time sensitive, which occurred at the early stage of differentiation. In the presence of AOPPs, induction of preadipocytes differentiation resulted in upregulated expression of C/EBP homologous protein (CHOP) and CUG-Triplet repeat-binding protein (CUGBP), two important inhibitors of preadipocytes differentiation. In addition, treatment with AOPPs increased abundance of C/EBP-β-liver enriched inhibitory protein (C/EBP-β-LIP), a truncated C/EBP-β isoform without adipogenic activity. Moreover, AOPPs-treated preadipocytes expressed a macrophage marker F4/80 and overexpressed tumor necrosis factor-α and interleukin-6 via nuclear factor-κB (NF-κB)-dependent pathway. However, blocking inflammation with NF-κB inhibitor failed to improve AOPPs-induced inhibition of preadipocytes differentiation. These data suggest that accumulation of AOPPs may inhibit differentiation of preadipocytes and activate inflammation in these cells. This information might have implication for understanding the impairment of preadipocytes differentiation and fat inflammation seen in metabolic syndrome. J. Cell. Physiol. 225: 42–51, 2010. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

In this article, we aim to develop a conceptual framework from a community perspective to examine the noneconomic effects of ethnic entrepreneurship, paying close attention to the linkage between entrepreneurship and community building. We base our analysis on ethnographic data from our comparative case studies of the Chinese and Korean enclave economies in Los Angeles. We argue that it is the social embeddedness of entrepreneurship, rather than individual entrepreneurs per se, that creates a unique social environment conducive to upward social mobility. This study suggests that ethnic entrepreneurship plays a pivotal role in immigrant adaptation beyond observable economic gains. Policy implications are discussed. © 2010 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Phytopathogenic bacteria inject an array of effector proteins into host cells to alter host physiology and assist the infection process. Some of these effectors can also trigger disease resistance as a result of recognition in the plant cell by cytoplasmic immune receptors. In addition to effector-triggered immunity, plants immunity can be triggered upon the detection of Pathogen/Microbe-Associated Molecular Patterns by surface-localized immune receptors. Recent progress indicates that many bacterial effector proteins use a variety of biochemical properties to directly attack key components of PAMP-triggered immunity and effector-triggered immunity, providing new insights into the molecular basis of plant innate immunity. Emerging evidence indicate that the evolution of disease resistance in plants is intimately linked to the mechanism by which bacterial effectors promote parasitism. This review focuses on how these studies have conceptually advanced our understanding of plant–pathogen interactions. [ABSTRACT FROM AUTHOR]

Sympathetic outflow is increased in hypertension. The aim of the present study was to investigate whether the cardiac sympathetic afferent reflex (CSAR) is enhanced in two-kidney one-clip (2K1C) renovascular hypertensive rats, and whether the enhanced CSAR contributes, in part, to the increased sympathetic outflow. Furthermore, the role of central angiotensin II type 1 (AT1) receptors in mediating the CSAR was determined. Under urethane and α-chloralose anaesthesia, the renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded in sinoaortic denervated and cervical vagotomized rats. The CSAR was evaluated by the response of RSNA and MAP to epicardial application of 1.0 nmol of capsaicin. Compared with sham-operated rats, the CSAR, baseline RSNA and plasma noradrenaline level were significantly enhanced in 2K1C rats. Intrapericardial administration of resiniferatoxin, which abolishes the CSAR because of the desensitization of transient receptor potential vanilloid 1-containing cardiac afferent fibres, decreased the RSNA and MAP. The enhanced CSAR in 2K1C rats was normalized by intracerebroventricular administration of the AT1 receptor antagonist losartan. Intracerebroventricular administration of angiotensin II further potentiated the enhanced CSAR in 2K1C rats, a response which was abolished by pretreatment with losartan. These results indicate that the CSAR is enhanced in 2K1C rats and the enhanced CSAR contributes, in part, to the sympathetic activation and hypertension. Central AT1 receptors are involved in the enhanced CSAR in 2K1C rats. [ABSTRACT FROM AUTHOR]

A genome comparison method was used to identify specific target sequences for the polymerase chain reaction (PCR) detection of Vibrio parahaemolyticus, and the CDS value of this bacterium was compared with that of 139 other bacterial genomes. It was found that 20 CDS of V. parahaemolyticus were relatively specific according to their E value in BLAST (a new tool for comparing protein and nucleotide sequences), and four of them were selected for the design of PCR primers. There were positive amplification products of these four pairs of primers from nine V. parahaemolyticus strains, whereas there were no amplification products from nine other Vibrionaceae strains and four non-Vibrionaceae strains. An evaluation of detection sensitivities revealed that these four pairs of primers can be used in a PCR assay for the detection of V. parahaemolyticus. PRACTICAL APPLICATIONS An automatic BLAST method was developed in this study, by which species-specific sequences can be screened out rapidly. In this way, new and specific genes of Vibrio parahaemolyticus were identified to be used as target sequences for PCR detection. In terms of acceptable specificity and sensitivity, the four pairs of primers were selected by screening, which can be applied in PCR assays and other molecular methods. These kinds of methods might become commercial detection products in the new future. In addition, this method for searching specific DNA sequences can also be used for the mining specific sequences in other genus and species, such as Salmonella, Staphylococcus, etc. [ABSTRACT FROM AUTHOR]

To overcome shortcomings of current small-diameter vascular prostheses, we developed a novel allogenic vascular graft from a decellularized scaffold modified through heparin immobilization and vascular endothelial growth factor (VEGF) coating. The VEGF coating and release profiles were assayed by enzyme-linked immunosorbent assay, the biological activity of modified surface was validated by human umbilical vein endothelial cells seeding and proliferation for 10 days in vitro. In vivo, we implanted either a modified or a nonmodified scaffold as bilateral carotid allogenic graft in canines ( n = 15). The morphological examination of decellularized scaffolds showed complete removal of cellular components while the extracellular matrix structure remained intact. After modification, the scaffolds possessed local sustained release of VEGF up to 20 days, on which the cells cultured showed significantly higher proliferation rate throughout the time after incubation compared with the cells cultured on nonmodified scaffolds ( P < 0.0001). After 6 months of implantation, the luminal surfaces of modified scaffolds exhibited complete endothelium regeneration, however, only a few disorderly cells and thrombosis overlay the luminal surfaces of nonmodified scaffolds. Specifically, the modified scaffolds exhibited significantly smaller hyperplastic neointima area compared with the nonmodified, not only at midportion (0.56 ± 0.07 vs. 2.04 ± 0.12 mm2, P < 0.0001), but also at anastomotic sites (1.76 ± 0.12 vs. 3.67 ± 0.20 mm2, P < 0.0001). Moreover, modified scaffolds had a significantly higher patency rate than the nonmodified after 6 months of implantation (14/15 vs. 7/15, P = 0.005). Overall, this modified decellularized scaffold provides a promising direction for fabrication of small-diameter vascular grafts. [ABSTRACT FROM AUTHOR]

The objectives of this study are to investigate the carriage rate of Candida albicans from the patients with oral lichen planus (OLP, erosive and non-erosive subtypes) and the healthy control individuals in a Chinese cohort and then to compare the virulence attributes of these isolates. Oral C. albicans isolates from 300 patients with OLP as well as 128 healthy controls were isolated and a total of 112 isolates from patients with erosive OLP (62), non-erosive OLP (24) and healthy control (26) were screened for phospholipase activity by using an in vitro plate assay method. Adhesion ability of the above isolates was also studied by using buccal epithelial cells assay. Statistically, the carriage rate of C. albicans from the patients with erosive OLP (44.29%) was higher than that of patients with non-erosive OLP (15.00%) or the healthy control group (20.31%) ( P < 0.001). The adhesion to buccal epithelial cells of the isolates from the erosive OLP group (3.950 ± 1.436) was more marked ( P < 0.001) than that from healthy control (2.2112 ± 0.4833). The phospholipase activity of these isolates either from erosive (0.4170 ± 0.029) or non-erosive OLP groups (0.4327 ± 0.028) was higher ( P < 0.001) than that from healthy controls (0.5259 ± 0.074). Some C. albicans isolates with special virulence attributes might be co-factors, which contribute to the development of OLP, especially erosive OLP. [ABSTRACT FROM AUTHOR]

Wheat flavone O-methyltransferase catalyzes three sequential methylations of the flavone tricetin. Like other flavonoid O-methyltransferases, the protein is a homodimer. We demonstrate, using analytical ultracentrifugation, that perchlorate dissociates the dimer into monomers. The resulting monomers retain all their catalytic capacity, including the ability to catalyze the three successive methylations. We show, using isothermal titration calorimetry, that the binding constant for S-adenosyl-l-methionine does not change significantly as the protein dissociates. The second substrate, tricetin, binds to the dimers but could not be tested with the monomers. CD, UV and fluorescence spectroscopy show that there are substantial changes in the structure of the protein as it dissociates. The fact that there are differences between the monomers and dimers even as the monomers maintain activity may be the result of the very low catalytic capacity of this enzyme. Maximal turnover numbers for the dimers and monomers are only about 6–7 per minute. Even though the binding pockets for S-adenosyl-l-methionine, tricetin, selgin and tricin are intact, selection of a catalytically competent structure may be a very slow step during catalysis. [ABSTRACT FROM AUTHOR]

Candida albicans carriage has been found to be increased in patients with oral lichen planus. In the present work we have investigated the genotypic profiles of 112 C. albicans strains isolated from patients with erosive or nonerosive OLP , and from healthy controls. The virulence attributes of the isolated strains were compared to elucidate the pathogenetic mechanisms through which C. albicans may cause OLP. We have characterized the genotypic profiles of these isolated strains using a randomly amplified polymorphic DNA assay. In addition, we used assays to measure adhesion to buccal epithelial cells and phospholipase activity to evaluate the virulence attributes of these isolates. Our RAPD analyses revealed four different genotypes, named type A to D, among all isolates, and identified statistically significant associations with disease conditions. Specifically, type A (58.1%) and C (29.0%) were primarily found in erosive OLP, while type A (33.3%) and D (58.3%) were identified in nonerosive OLP. However, the healthy group seemed to have type B (38.5%) and D (61.5%). Using adhesion to BEC assay, we demonstrated that the isolates with genotype A had the strongest adherence among the four genotypes (P=0.000<0.05). The phospholipase activity of the isolates with genotype A and C was higher than for those with genotype B and D (P=0.000<0.05). In conclusion, some C. albicans isolates with special genotypic profiles and virulence attributes may contribute to the pathogenesis of OLP. [ABSTRACT FROM AUTHOR]

Background: Radiation therapy (RT) to the left breast/chest wall has been linked with cardiac dysfunction. Previously, the authors identified cardiac perfusion defects in approximately 50% to 60% of patients 0.5 to 2 years post-RT. In the current study, they assessed the persistence of these defects 3 to 6 years post-RT. Methods: From 1998 to 2006, 160 patients with left-sided breast cancer were enrolled onto an Institutional Review Board-approved, prospective study. All patients received tangential photons to the left breast/chest wall. Patients had pre-RT and serial post-RT single-photon emission computed tomography (SPECT) scans to assess changes in regional cardiac perfusion, wall motion, and ejection fraction (EF). Forty-four patients had SPECT scans 3 to 6 years post-RT and were evaluable for the current analysis. Results: The overall incidence of perfusion defects at 3 years, 4 years, 5 years, and 6 years was 52% (11 of 21 patients), 71% (17 of 24 patients), 67% (12 of 18 patients), and 57% (4 of 7 patients), respectively. The rate of abnormal SPECT scans 3 to 6 years post-RT in patients who had scans at 0.5 to 2 years that were either all abnormal, intermittently abnormal, or all normal was 80%, 67%, and 63%, respectively. The incidence of wall motion abnormalities in patients with or without perfusion defects 3 to 6 years post-RT was low and did not differ statistically (17% vs 7.1%, respectively; P = .65), as was the incidence of reductions in EF of >/=5% (27% vs 36%, respectively; P = .72). Conclusions: The results from this study indicated that RT-induced perfusion defects may persist or initially may appear 3 to 6 years post-RT in a high percentage of patients. However, these defects were not associated with changes in regional wall motion or EF. Additional study will be needed to determine the clinical relevance of these defects. In the meantime, the authors believe that every effort should be made to minimize incidental irradiation of the heart while maintaining adequate coverage of target volumes. [ABSTRACT FROM AUTHOR]

Traditional methods to compute the tumor control probability (TCP) or normal tissue complication probability (NTCP) typically require a heterogeneous radiation dose distribution to be converted into a simple uniform dose distribution with an equivalent biological effect. Several power-law type dose-volume-histogram reduction schemes, particularly Niemierko’s generalized equivalent uniform dose model [Med. Phys. 26, 1000 (1999)], have been proposed to achieve this goal. In this study, we carefully examine the mathematical outcome of these schemes. We demonstrate that (1) for tumors, with each tumor cell independently responding to local radiation dose, a closed-form analytical solution for tumor survival fraction and TCP can be obtained; (2) for serial structured normal tissues, an exponential power-law form relating survival to functional sub-unit (FSU) radiation is required, and a closed-form analytical solution for the related NTCP is provided; (3) in the case of a parallel structured normal tissue, when NTCP is determined solely by the number of the surviving FSUs, a mathematical solution is available only when there is a non-zero threshold dose and/or a finite critical dose defining the radiotherapy response. Some discussion is offered for the partial irradiation effect on normal tissues in this category; (4) for normal tissues with alternative architectures, where the radiation response of FSU is inhomogeneous, there is no exact global mathematical solution for SF or NTCP within the available schemes. Finally, numerical fits of our models to some experimental data are also presented. [ABSTRACT FROM AUTHOR]

Synaptic long-term depression (LTD) is thought to be important for various brain functions such as learning, memory, and development. Although anterior cingulated cortex (ACC) has been demonstrated to contribute to learning and memory, no studies has been reported about the synaptic mechanisms for cingulate LTD. Here, we used integrative genetic, pharmacological and electrophysiological approaches to demonstrate that AMPA GluR2, but not GluR3, subunit is critical for cingulate LTD. We found that LTD was absent in adult cingulate slices of GluR2 knockout mice. Furthermore, postsynaptic injections of peptides that inhibit AMPA GluR2-PDZ interactions blocked the induction of LTD. To determine if the requirement for AMPA receptor-PDZ interaction is time-dependent, we injected the same inhibiting peptide into the postsynaptic cells 5 min after the induction of LTD. We found that LTD was not affected by the peptide, providing the first evidence that postsynaptic AMPA GluR2-mediated depression occurs rapidly (within t = 5 min). Genetic deletion of GluR3 did not affect cingulate LTD. Our results provide the first study of cingulate LTD mechanism using whole-cell patch-clamp recording in adult cortical slices and demonstrate that postsynaptic AMPA GluR2 subunit is crucial for synaptic depression in the ACC of adult mice. J. Cell. Physiol. 211: 336–343, 2007. © 2006 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

This article discusses findings of a study, which examined the role of CD1d-reactive invariant natural killer T (iNKT) cells in the development of autoimmune disease in genetically lupus-prone mice. Diverse sets of T helper cells can promote autoantibody production in humans and animals with systemic lupus erythematosus (SLE). NKT cells produce interleukin-4 (IL-4) and it may be comprised of 2 subsets, like CD4+ T cells and double-negative (DN) T cells.

Immobilized patients, diabetics, and the elderly suffer from impaired wound healing. The 43-amino acid angiogenic peptide thymosin β4 (Tβ4) has previously been found to accelerate dermal wound repair in rats, aged mice, and db/db diabetic mice. It also promotes corneal repair in both normal rats and mice. Because proteinases are important in wound repair, we hypothesized that Tβ4 may regulate matrix metalloproteinase (MMP) expression in cells that are involved in wound repair. Analysis by RT-PCR of whole excised mouse dermal wounds on days 1, 2, and 3 after wounding showed that Tβ4 increased several metalloproteinases, including MMP-2 and -9 expression by several-fold over control on day 2 after wounding. We further analyzed the metalloproteinases secreted in response to exogenous Tβ4 by cells normally present in the wound. Western blot analysis of cultured keratinocytes, endothelial cells, and fibroblasts that were treated with increasing concentrations of Tβ4 showed increases in the levels of MMP-1, -2, and -9 in a cell-specific manner. Tβ4 also enhanced the secretion of MMP-1 and MMP-9 by activated monocytes. The central actin-binding domain, amino acids 17–23, had all of the activity for metalloproteinase induction. We conclude that part of the wound healing activity of Tβ4 resides in its ability to increase proteinase activity via its central actin-binding domain. Thus, Tβ4 may play a pivotal role in extracellular matrix remodeling during wound repair. J. Cell. Physiol. © 2006 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Two new compounds, 1-(3-methoxy-4-hydroxyphenyl)-3-(3, 5-dimethoxy-4-hydroxyphenyl)-propane (1) and 5, 7, 3′-trimethyoxyflavan-4′-O-β- D-glucopyranoside (2) were isolated from the ethanol extract of the dried aerial parts of Phacellaria compressa Benth., together with 2,3-bis[(4-hydroxy-3,5-dimethoxyphenyl)-methyl]-1,4-butanediol (3), ethyl 3,4,5-trihydroxybenzoate (4), methyl 3, 4, 5-trihydroxybenzoate (5), β-sitosterol (6), 5, 7, 3′, 4′-tetrahydroxyflavan (7), lupeol (8), zhebeiresinol (9), quercetin-3-O-α- L-rhamnopyranoside (10), (+)-catechin (11), betulin (12), β-daucosterol (13), (+)-syringaresinol (14), scopoletin (15), and proximadiol (16). The structures of these compounds were determined by spectral evidence or by comparing them with authentic samples. Compound 9 showed α-amylase inhibitory activity of 57.55% at a concentration of 50 μg/mL. (Managing editor: Wei Wang) [ABSTRACT FROM AUTHOR]