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The efficiency of hydrogen negative ion production in negative ion sources depends on the work function of the molybdenum surface. Deposition of cesium (Cs) atoms on the Mo surface reduces the work function from over 4.0 eV to about 1.50–1.80 eV. However, the Fermi level remains below the affinity level (−0.75 eV) of hydrogen negative ions. To explore further reduction methods, the work function of Cs co-adsorbed with fluorine on the Mo (001) surface was studied using DFT calculations. The results show that at 4/16 θ Cs coverage, adding fluorine can reduce the work function, achieving the lowest value of 1.40 eV at 8/16 θ F coverage. Analysis reveals a significant vacuum-inward dipole moment with fluorine-Cs co-adsorption, favorably reducing the work function. However, fluorine’s strong electronegativity also creates a surface-directed dipole moment, increasing the work function. Introducing fluorine is beneficial only at 4/16 θ Cs coverage, indicating that precise control of Cs coverage is necessary to achieve lower work functions.

The continuous activation of macrophages play a critical role in the pathogenesis of cytokine storm (CS). Considering that CS results from the participation of multiple cytokines, the therapeutic effect of a single cytokine or its receptor-targeted blockade therapy remains uncertain. Melittin, which can systematically suppress the overexpression of proinflammatory mediators via inhibiting the mitogen-activated protein kinase and nuclear factor kappa-B pathways in activated macrophages, shows great potential in alleviating CS and acute inflammatory injury (AII). However, its clinical application is limited by its hemolytic activity, non-specific cytotoxicity and lack of targeting. In this study, a folic acid-modified and melittin stable-loaded solid lipid nanoparticle (Fa-MpG@LNP) with a core–shell structure was developed for CS control via targeted inhibition of the overproduction of proinflammatory mediators in activated macrophages with specific expression of folate receptor-β. The resultant Fa-MpG@LNP showed ideal physicochemical properties and stability, low hemolytic activity and non-specific cytotoxicity, and it can specifically bind to lipopolysaccharide (LPS)-stimulated macrophages and effectively reduce the elevated levels of proinflammatory mediators. After intravenous administration, the Fa-MpG@LNP accumulated at inflamed tissue and significantly downregulate the overproduction of proinflammatory cytokines in tissue-infiltrated macrophages, resulting in a significant decrease of cytokine concentration in inflamed tissue and serum in LPS-induced acute pneumonia mice, and finally alleviate AII with undetectable toxic side effects. These results indicate the clinical application potential of Fa-MpG@LNP in alleviating CS and its related symptoms.

A two-dimensional symmetric fluid model is established to study the influence of radio frequency (RF) wave driving frequency on the capacitively coupled plasma discharge. The relationship between the driving frequency and electron density is obtained by solving the electron energy balance equation. The calculation results show that the average electron density first increases rapidly with the increase in driving frequency and then gradually tends to saturation at a threshold frequency. A fluid simulation is also carried out, which provides similar results. Physical studies on this phenomenon are conducted, revealing that the essence of this phenomenon is due to the inability of electrons to quickly respond to potential changes within the boundary sheath when the driving frequency of RF exceeds the plasma frequency. In addition, it is also found that increasing gas pressure can enhance the electron density and the type of gas can also affect the electron density.

Abstract In the realm of malignant tumor treatment, particularly regarding hematologic malignancies, chimeric antigen receptor T‐cell (CAR‐T) immunotherapy has witnessed remarkable advancements in recent years. This approach involves genetically modifying and engineering a patient's T‐cells ex vivo to express a specific CAR, known as CAR‐T cells. When these modified cells are reintroduced into the patient, they can specifically recognize target antigens and exhibit highly efficient cytotoxicity against cells expressing these antigens, making them suitable for the treatment of malignant tumors. CD19, which is expressed on the surface of B lymphocytes at different stages of differentiation, has been identified as a suitable target for the treatment of most B‐cell lymphomas. CAR‐T cells targeting CD19 have demonstrated excellent specificity, cytotoxicity, and persistence in both in vitro and clinical trials, showing tremendous potential for application. However, identifying appropriate targets for CAR‐T therapy in solid tumors remains a challenge, leading to limited advancements in this area. This review discusses the mechanisms, applications, limitations, and prospects of CAR‐T therapy in hematologic malignancies and solid tumors, aiming to provide directions for future research in this field.

Based on the DFT method, the effects of copper and tungsten impurities present in the negative ion source of neutral beams on the cesiated surface were studied, including their effects on the adsorption energy of cesium on the surface and the surface work function. The results indicate that copper impurities significantly increase the average adsorption energy of cesium, whereas tungsten has limited enhancement on the average adsorption energy of cesium and may even reduce it. The work function calculations show that, at cesium coverages below 4/16 θ, copper impurities cause a significant increase in the work function. However, at cesium coverages above 6/16 θ, high-coverage copper impurities lead to a further decrease in the work function, causing the cesium coverage corresponding to the lowest work function to shift towards higher cesium coverage. Under any tungsten impurity and cesium coverage, tungsten impurities can significantly increase the surface work function, with the maximum increase reaching 0.50 eV. The dipole moment density analysis shows that in most cases, impurities significantly reduce the dipole moment density of the cesiated surface, except when the coverage of cesium and copper impurities is above 6/16 θ. The charge transfer results show that the copper impurity layer has more positive charge compared to the tungsten impurity layer, which significantly affects the dipole moment density of the surface system. In addition, adsorbed atoms cause electrons in the molybdenum atomic layer to migrate to the surface, resulting in the molybdenum substrate having a pronounced negative dipole moment.

The impact of H atoms and O impurities on the adsorption stability and work function of cesiated Mo (001) surface are investigated in this paper through DFT calculations. The 53 surface structures with different surface coverages are constructed in this work. Two types of co-deposition structures are considered: Cs-O (or Cs-H) bonds (1) leaning towards and (2) perpendicular to the surface. Our results demonstrate that the minimum work function corresponds to a 0.5 ML coverage of Cs for any surface coverage of H (or O) when the bonds are tilted. Compared to pure Cs deposition, the work function of Cs and H (or O) co-deposition surface increases at low or saturated Cs coverage, while decreases at 0.5 ML. Analysis of the surface dipole moment revealed that the work function changed inversely with the surface dipole moment density. Comparing charge transfer and polarization, it is evident that charge polarization has a significant impact on dipole moment changes. The presence of O impurities significantly enhances the adsorption stability of Cs, with higher coverage of O impurities leading to greater adsorption stability. The average adsorption energy of Cs atoms increases by ∼0.36 eV when co-deposits with O (0.5 θ). The effect of the H atoms on the adsorption stability of Cs atoms is limited. We also find that the vertical co-deposition case did not offer an advantage in terms of adsorption stability and low work function.

Since the last IAEA-FEC in 2021, significant progress on the development of long pulse steady state scenario and its related key physics and technologies have been achieved, including the reproducible 403 s long-pulse steady-state H-mode plasma with pure radio frequency (RF) power heating. A thousand-second time scale (∼1056 s) fully non-inductive plasma with high injected energy up to 1.73 GJ has also been achieved. The EAST operational regime of high β _P has been significantly extended ( H _98y2 > 1.3, β _P ∼ 4.0, β _N ∼ 2.4 and n _e / n _GW ∼ 1.0) using RF and neutral beam injection (NBI). The full edge localized mode suppression using the n = 4 resonant magnetic perturbations has been achieved in ITER-like standard type-I ELMy H-mode plasmas with q _95 ≈ 3.1 on EAST, extrapolating favorably to the ITER baseline scenario. The sustained large ELM control and stable partial detachment have been achieved with Ne seeding. The underlying physics of plasma-beta effect for error field penetration, where toroidal effect dominates, is disclosed by comparing the results in cylindrical theory and MARS-Q simulation in EAST. Breakdown and plasma initiation at low toroidal electric fields (

Abstract As a kind of carcinoma with increasing morbidity, poor prognosis, and high mortality, esophageal squamous cell carcinoma (ESCC) is challenging for clinical management. Chemotherapy has been the standard treatment for ESCC over decades, while its clinical outcomes remain unsatisfying. And the regimen that combine standard chemotherapy with targeted therapy also demonstrates little effect. However, the advent of immune checkpoint inhibitors (ICI) proved to be a game changer in cancer treatment. Recent clinical trials had sprung up to evaluate the combined effect of ICI and chemotherapy regarding first‐line ESCC treatment. What's more, researchers attempt to explore the possibility to implement ICI monotherapy regarding second‐line ESCC treatment. In conclusion, most of the first‐line trails present inspiring achievement, while ICI monotherapy indicates little improvement for ESCC treatment. To point out the heterogenicity that could be the potential reasons biasing the pooled results, the differences of PD‐L1 immunohistochemistry (IHC) assays, geographic regions, chemotherapy regimens, and sex disparity among these trails are discussed respectively. In addition, the adverse events occurred during the trails are summarized, which confirm the safety of immunotherapy and chemoimmunotherapy. The article comprehensively reviews the representative explorations of using chemoimmunotherapy strategies in ESCC, as well as the deficiencies among them. Moreover, we highlight some feasible approaches. It will be beneficial for conducting more precise clinical trials on chemoimmunotherapy for ESCC in the future, including the use of more appropriate PD‐L1 IHC assays, careful consideration of the heterogeneity of the enrolled population and the optimal combination of chemotherapy and ICI.

We studied the work function of cesium deposition and co-deposition with the electronegative element on the plasma grid (PG) using the first-principles calculations. The impurity particles may exist in the background plasma and vacuum chamber wall, and the work function of the PG will be affected. The results indicate that the minimum work functions of pure cesium deposition on Mo (110), W (110), and Mo (112) are reached at a partial monolayer. They are 1.66 eV (σ = 0.56 θ), 1.69 eV (σ = 0.75 θ), and 1.75 eV (σ = 0.88 θ), respectively. An appropriate co-deposition model consisting of cesium with electronegative elements can further decrease the work function. The coverage of cesium and electronegative elements are both 0.34 θ in all the co-deposition models. The F-Cs co-deposition model where the Cs atom and F atom are aligned along the surface normal obtains the lowest work function. They are 1.31 eV for F-Cs on Mo (110), and 1.23 eV for F-Cs on W (110), respectively. The change in work function is linearly related to the change in dipole moment density with a slope of −167.03 VÅ. For pure cesium deposition, two factors control the change in dipole-moment density, one is the electron transfer between adsorbates and the substrate, and another one is the restructuring of surface atoms. There are two additional factors for the co-deposition model. One is the intrinsic dipole moment of the double layer, the other is the angle between the intrinsic dipole moment and the surface. The latter two factors play important roles in increasing the total dipole moment.

T cells are one of the most important effector cells in cancer immunotherapy. Various T cell-dependent bispecific antibody (TDB) drugs that engage T cells for targeted cancer cell lysis are being developed. Here, we describe supra-molecular T-cell redirecting antibody fragment-anchored liposomes (TRAFsomes) and report their immune modulation and anti-cancer effects. We found that TRAFsomes containing different copies of anti-CD3 fragments displayed different T cell modulation profiles, showing that optimization of surface density is needed to define the therapeutic window for potentiating cancer cell-specific immune reactions while minimizing nonspecific side effects. Moreover, small molecular immunomodulators may also be incorporated by liposomal encapsulation to drive CD8 + T cell biased immune responses. In vivo studies using human peripheral blood mononuclear cell reconstituted mouse models showed that TRAFsomes remained bounded to human T cells and persisted for more than 48 hours after injection. However, only TRAFsomes containing a few anti-CD3 (n = 9) demonstrated significant T cell-mediated anti-cancer activities to reverse tumor growth. Those with more anti-CD3s (n = 70) caused tumor growth and depletion of human T cells at the end of treatments. These data suggested that TRAFsomes can be as potent as traditional TDBs and the liposomal structure offers great potential for immunomodulation and improvement of the therapeutic index.Abbreviation: Chimeric antigen receptor T cells (CAR-T cells), Cytokine release syndrome (CRS) Cytotoxic T cell (CTL) Effector: target ratios (E:T ratios), Heavy chain (HC) Immune-related adverse events (irAE), Large unilamellar vesicle (LUV), Peripheral blood mononuclear cells (PBMCs, Single-chain variable fragment (scFv), T cell-dependent bispecific antibody (TDB), T cell redirecting antibody fragment-anchored liposomes (TRAFsomes), Methoxy poly-(ethylene glycol) (mPEG)

The pathology of psoriasis involves the over-proliferation of keratinocytes, exaggerated inflammation of keratinocytes, and infiltration of inflammatory cells such as macrophages (Mø), etc. The therapeutic outcomes of current treatment targeting one single pathological process are less than satisfactory. Based on their diverse biological activities, natural products offer a potential solution to this problem. In this study, we investigated the effects of β-Elemene (ELE) on both psoriatic keratinocytes and M1-type Mø (M1-Mø) in vitro. Hyaluronic acid (HA) microneedles loaded with ELE (HA-ELE-MN) were also fabricated and tested for the treatment of psoriasis in vivo using an imiquimod (IMQ)-induced psoriatic mice model. Our data suggest that ELE induces apoptosis and inhibits inflammation of psoriatic keratinocytes. In addition, ELE attenuates the expression of inflammatory cytokines secreted from M1-Mø, thus indirectly inhibiting the inflammation of keratinocytes. Furthermore, HA-ELE-MN has been found to significantly alleviate symptoms in an IMQ-induced psoriatic mice model by inducing keratinocytes apoptosis, suppressing keratinocytes proliferation, and inhibiting M1-Mø infiltration. Taken together, this study demonstrates that ELE can be used for the treatment of psoriasis by targeting both keratinocytes and M1-Mø, which provides a potential novel reagent for psoriasis treatment.

Abstract Accurate prognosis prediction is the key to achieving precision treatment and guiding the selection of adjuvant chemotherapy in high‐risk stage II/III colorectal cancer (CRC) patients. Here we developed a novel machine learning method, the random non‐negative matrix factorization (RNMF) algorithm, which outperformed traditional non‐negative matrix factorization in terms of computational speed, accuracy, and robustness in simulated data sets. Moreover, based on multidimensional data from CRC patients from The Cancer Genome Atlas database and DNA methylation data from those from Sun Yat‐sen University cancer center, we further demonstrated the excellent performance of a novel prognostic computational framework based on the RNMF (PCF_RNMF), which is capable of integrating multidimensional training while allowing survival prediction when single dimensional data for validation is provided. This novel algorithm has great potential to mitigate the challenge of integrating various types of data in public databases with clinically available single‐dimensional data to allow cost‐effective survival prediction for CRC patients in clinical practice.

Molecular dynamic simulation is used to simulate the corrosion process of Fe or Ni in liquid Cs by Large-scale Atomic/Molecular Massively Parallel Simulator. The embedded-atom method potential is used to describe the interaction of Fe–Fe, Ni–Ni, and Cs–Cs, and Morse two-body potential is used to describe the Fe–Cs and Ni–Cs atomic interaction. Temperature is considered as a critical condition in this work. Results indicate that corrosion is easy to occur in the systems. The increase in temperature can help the process of Cs corrosion. Compared to the Ni–Cs system, the Fe–Cs system has a higher atomic concentration function. The radial distribution function shows that Cs atoms are dissolved into the substrates, but the Fe and Ni substrates are still crystalline structures. Moreover, Cs in Fe or Ni is still a liquid phase.

In future fusion reactors, the confinement of α-particles is a crucial issue. The perfect omnigenity may be difficult to achieve in the quasi-isodynamic and quasi-symmetric stellarators when a multi-objective optimization is considered. Non-axisymmetric field can result in collisionless particles’ transport via localized trapping by ripples. Specific loss channels have been revealed to essentially exist in quasi-axisymmetric stellarators [Yang et al., Europhys. Lett. 129, 35001 (2020)] and W7-X [J. M. Faustin et al., Nucl. Fusion 56, 092006 (2016)]. It indicates a drastic loss of collisionless ions through these channels. This paper is devoted to investigate the effects of axisymmetry-breaking magnetic fields on collisionless α-particle transport in the CFQS (Chinese First Quasi-axisymmetric Stellarator) -like reactor configuration. A semi-analytic representation of radial and poloidal drifts in Boozer coordinates is given, by which we found an effective route to mitigate α-particle losses, i.e., adjusting the location of the quasi-axisymmetric radial position. Such a route enables the enhancement of the poloidal drift and decrease of radial drift in peripheral regions of the identified loss channels. The particles launched inside the quasi-axisymmetric radial surface can be well confined because localized particles that may fall in loss channels can transit into blocked particles near the quasi-axisymmetric surface, escaping from loss channels, which is beneficial for the improvement of the particle confinement. Moreover, this paper may provide a set of proxy functions for suppression of energetic particle losses to optimize stellarator configurations.

Myeloid Derived Suppressor Cells (MDSCs) play important roles in constituting the immune suppressive environment promoting cancer development and progression. They are consisted of a heterogeneous population of immature myeloid cells including polymorphonuclear MDSC (PMN-MDSC) and monocytes MDSC (M-MDSC) that are found in both the systemic circulation and in the tumor microenvironment (TME). While previous studies had shown that all-trans retinoic acid (ATRA) could induce MDSC differentiation and maturation, the very poor solubility and fast metabolism of the drug limited its applications as an immune-modulator for cancer immunotherapy. We aimed in this study to develop a drug encapsulated liposome formulation L-ATRA with sustained release properties and examined the immuno-modulation effects. We showed that the actively loaded L-ATRA achieved stable encapsulation and enabled controlled drug release and accumulation in the tumor tissues. In vivo administration of L-ATRA promoted the remodeling of the systemic immune homeostasis as well as the tumor microenvironment. They were found to promote MDSCs maturation into DCs and facilitate immune responses against cancer cells. When used as a single agent treatment, L-ATRA deterred tumor growth, but only in immune-competent mice. In mice with impaired immune functions, L-ATRA at the same dose was not effective. When combined with checkpoint inhibitory agents, L-ATRA resulted in greater anti-cancer activities. Thus, L-ATRA may present a new IO strategy targeting the MDSCs that needs be further explored for improving the immunotherapy efficacy in cancer.

Neoclassical properties in quasi-axisymmetric (QA) stellarators are analogous to these in tokamaks. Consequently, a substantial bootstrap current could significantly modify the MHD equilibrium properties of a QA stellarator, which is an important characteristic in this type of stellarator. This paper is dedicated to systemically investigate the effects of bootstrap current on the magnetic configuration in Chinese first quasi-axisymmetric stellarator (CFQS). For the first time, self-consistent bootstrap currents in free-boundary equilibria are calculated with an accurate Fokker–Planck neoclassical numerical mode in CFQS. Several important results are achieved: (a) as the bootstrap current grows with increasing volume-averaged normalized pressure $\beta $ , magnetic shear develops in the bulk plasma and meanwhile, a deep magnetic well is robustly sustained, which leads to improved stabilization of interchange modes up to $\beta \sim 2.0{{\% }}$ . (b) In the analysis of global ideal MHD instability, as the bootstrap current rises to 39 kA ( $\beta \sim 1.3{{\% }}$ ), external kink modes become destabilized and the unstable mode with m / n = 2/1 is dominant. (c) From $\beta = 0$ to 1.5%, the bootstrap current hardly changes the QA property and a low neoclassical transport is maintained. However, as $\beta $ is enhanced beyond 2.0%, the substantial bootstrap current gives rise to an increase of non-QA magnetic field components, which weakens the neoclassical transport properties. (d) An increase of the negative magnetic shear at the core region by the bootstrap currents has a favorable effect on the properties of J (second adiabatic invariant). The maximum- J region can be extended by raising bootstrap currents.

The absorption of peptides and proteins delivered orally is minimum because of the intestine epithelial barrier. There are few known active transport mechanisms for macromolecules including the neonatal Fc Receptor (FcRn) for the absorption and secretion of IgGs in infant and adult intestine. We had previously described the FnAb-8 protein that could bind to hFcRn tightly at pH 6.0 but barely at pH 7.4. In this study, we examined its uptake, biodistribution and pharmacokinetics after peroral administration in both wild-type and human FcRn transgenic (Tg) mice. FnAb-8 was modified to contain trans-cyclooctene (TCO) which could interact with 18F labeled tetrazine in situ via the bioorthogonal inverse-electron-demand Diels−Alder reaction. We showed that FnAb-8 had a tendency to distribute and persist in the Tg mice intestine for an extended duration of time. It could also be absorbed into the circulation and distributed systemically over a long period of time up to 172 h. The improvement in oral uptake and concentration in the intestine tissue may be valuable for designing oral delivery of biopharmaceuticals, especially for diseases involving the gastric intestinal tissue.

Due to the presence of capacitance in the transmission line, the current collected by the retarding field analyzer (RFA) becomes asymmetrical (i.e., hysteresis) during voltage scanning, and it further affects the measurement of the ion temperature (Ti). In this article, we first analyze the hysteresis of the RFA’s I–V characteristics measured in the edge plasma of the J-TEXT tokamak, and we found that the ion temperature fitted from the falling side of the collector current is about 14% higher than that fitted from the rising side. An analytic model is built and verified by experimental results. Based on the model, the influence of the capacitance of transmission lines and the frequency of the scanning voltage on the hysteresis is investigated. It is found that the hysteresis becomes more remarkable with increasing capacitance or scanning frequency. Besides, the impact of the capacitance and the scanning frequency on the Ti measurement is also studied, which indicates that Ti is overestimated due to the hysteresis. The temperature error is linearly dependent on the capacitance and the scanning frequency. Furthermore, the analytical results are expected to be used in the prediction of scanning frequency for RFA applications.

Liposomes, as one of the most successful nanotherapeutics, have a major impact on many biomedical areas. In this study, we performed laser scanning confocal microscope (LSCM) and immunohistochemistry (IHC) assays to investigate the intra-tumor transport and antitumor mechanism of GE11 peptide-conjugated active targeting liposomes (GE11-TLs) in SMMC7721 xenograft model. According to classification of individual cell types in high resolution images, biodistribution of macrophages, tumor cells, cells with high epidermal growth factor receptor (EGFR) expression and interstitial matrix in tumor microenvironment, in addition, their impacts on intra-tumor penetration of GE11-TLs were estimated. Type I collagen fibers and macrophage flooded in the whole SMMC7721 tumor xenografts. Tumor angiogenesis was of great heterogeneity from the periphery to the center region. However, the receptor-binding site barriers were supposed to be the leading cause of poor penetration of GE11-TLs. We anticipate these images can give a deep reconsideration for rational design of target nanoparticles for overcoming biological barriers to drug delivery. Key words: GE11, Liposome, Target delivery, Biology barrier, EGFR, SMMC7721

The classification of high-dimensional data is a challenge in machine learning. Traditional classifier ensemble methods improve the diversity of classifiers through either dimensionality reduction or sample selection for high-dimensional data classification. However, these methods have several limitations: 1) dimensionality reduction methods easily cause information loss, which leads to a decrease in accuracy; 2) sample selection methods are susceptible to noise and redundant features. To address the above limitations, we propose a novel hybrid dimensionality reduction forest (HDRF) to increase the diversity of an integrated system from feature space and sample space. First, a tree-based feature selection algorithm is employed to partition effective features. Then the Bagging method is applied to obtain diverse training subsets. To fully retain and mine the important information of the unselected samples, a sample-feature based transformation process (SFTP) is proposed to generate the extended features. Since PCA can effectively reduce dimension and remove noise features, it is applied to compress the unselected features and the extended features into the new features which are compact and compensatory. Further, a novel classifier ensemble pruning framework (HDRFPF) based on HDRF is designed to remove redundant and invalid classifiers. Experimental results on 23 high-dimensional data sets verify that our method outperforms mainstream classifier ensemble methods, and the better results are obtained on 19 out of 23 datasets.

This paper generally compares the essential features between tokamaks and stellarators, based on previous review work individually made by authors on several specific topics, such as theories, bulk plasma transport and edge divertor physics, along with some recent results. It aims at summarizing the main results and conclusions with regard to the advantages and disadvantages in these two types of magnetic fusion devices. The comparison includes basic magnetic configurations, magnetohydrodynamic (MHD) instabilities, operational limits and disruptions, neoclassical and turbulent transport, confinement scaling and isotopic effects, plasma rotation, and edge and divertor physics. Finally, a concept of quasi-symmetric stellarators is briefly referred along with a comparison of future application for fusion reactors.

We present herein a novel method of pIII-based antibody phage display using Hpd3cells—bacterial cells bearing the genome of a gene-III-lacking helper phage (VCSM13d3). A high level of single-chain variable fragments (scFvs) was displayed in the consequent phagemid particles using Hpd3cells to rescue the phagemid encoding scFv-pIII. Hpd3cells considerably improved the specific enrichment factor when used for constructing an immunized antibody library. In addition, using Hpd3cells could overcome pIII resistance and can contribute to the efficient enrichment of specific binding antibodies from a phage display library, thereby increasing the chance of obtaining more diverse antibodies specific for target antigens.

[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) has been widely used in oncologic procedures such as tumor diagnosis and staging. However, false-positive rates have been high, unacceptable and mainly caused by inflammatory lesions. Misinterpretations take place especially when non-subcutaneous inflammations appear at the tumor site, for instance in the lung. The aim of the current study is to evaluate the use of dynamic PET imaging procedure to differentiate in situ and subcutaneous non-small cell lung carcinoma (NSCLC) from inflammation, and estimate the kinetics of inflammations in various locations.Dynamic FDG-PET was performed on 33 female mice inoculated with tumor and/or inflammation subcutaneously or inside the lung. Standardized Uptake Values (SUVs) from static imaging (SUVmax) as well as values of influx rate constant (Ki) of compartmental modeling from dynamic imaging were obtained. Static and kinetic data from different lesions (tumor and inflammations) or different locations (subcutaneous, in situ and spontaneous group) were compared.Values of SUVmax showed significant difference in subcutaneous tumor and inflammation (p

Ligand or peptide-targeted phagemid particles are being pursued as vehicles for receptor-mediated gene delivery. Here we describe a helper phage in which the protein III (pIII) protein is modified by the addition of a ligand peptide sequence at the amino terminus. Phagemid particles can be prepared with the help of this modified helper phage and should display the ligand peptide in most of the pIII proteins on the phagemid surface. Using such a method, it is not necessary for the phagemid to encode the pIII protein, which leaves a larger space for cloning genes of interest. In addition, the technique should allow for the rapid testing of peptide ligands selected from phage display libraries using phagemids encoding various reporter genes (e.g., green fluorescent protein, luciferase, β-galactosidase) and therapeutic genes.

BACKGROUND: A number of studies have been conducted to investigate the risk of metabolic syndrome (MS) after gestational diabetes mellitus (GDM), but the results are contradictory. Accordingly, we performed a systematic review and meta-analysis to assess the association between these two conditions. The aim was to better understand the risks of MS with prior gestational diabetes. METHODS: Pubmed, ISI Web of Science, and Cochrane databases from September 1, 1979 to July 11, 2013 were searched to identify relevant studies. 17 studies containing 5832 women and 1149 MS events were included. We calculated the odds ratio (OR) with 95% confidence interval (CI) in analysis for each study using a random-effect or fixed-effect model. We also determined heterogeneity among these 17 articles and their publication bias. RESULTS: Women with a history of gestational diabetes had a significantly higher risk of MS than those who had a normal pregnancy (OR, 3.96; 95% CI, 2.99 to 5.26), but had significant heterogeneity (I (2) = 52.6%). The effect remained robust (OR, 4.54; 95% CI, 3.78-5.46) in the subgroup of Caucasians, but no association (OR, 1.28; 95% CI, 0.64-2.56) was found in Asians. Heterogeneity was reduced (body mass index (BMI) matched group I (2) = 14.2%, BMI higher in the GDM group I (2) = 13.2%) in the subgroup of BMI. In addition, mothers with higher BMI in the GDM group had higher risk of MS than those in the BMI matched group (BMI higher in GDM group OR, 5.39; 95% CI, 4.47-6.50, BMI matched group OR, 2.53; 95% CI, 1.88-3.41). CONCLUSIONS: This meta-analysis demonstrated increased risk of MS after gestational diabetes. Therefore, attention should be given to preventing or delaying the onset of MS in GDM mothers, particularly in Caucasian and obese mothers.

Huperzine A is a bioactive compound derived from traditional Chinese medicine plant Qian Ceng Ta (Huperzia serrata), and was found to have multiple neuroprotective effects. In addition to being a potent acetylcholinesterase inhibitor, it was thought to act through other mechanisms such as antioxidation, antiapoptosis, etc. However, the molecular targets involved with these mechanisms were not identified. In this study, we attempted to exam the interactome of Huperzine A using a cDNA phage display library and also mammalian brain tissue extracts. The drugs were chemically linked on the surface of magnetic particles and the interactive phages or proteins were collected and analyzed. Among the various cDNA expressing phages selected, one was identified to encode the mitochondria NADH dehydrogenase subunit 1. Specific bindings between the drug and the target phages and target proteins were confirmed. Another enriched phage clone was identified as mitochondria ATP synthase, which was also panned out from the proteome of mouse brain tissue lysate. These data indicated the possible involvement of mitochondrial respiratory chain matrix enzymes in Huperzine A's pharmacological effects. Such involvement had been suggested by previous studies based on enzyme activity changes. Our data supported the new mechanism. Overall we demonstrated the feasibility of using magnetic biopanning as a simple and viable method for investigating the complex molecular mechanisms of bioactive molecules.

BACKGROUND: Phenazines are important compounds produced by pseudomonads and other bacteria. Two phz gene clusters called phzA1-G1 and phzA2-G2, respectively, were found in the genome of Pseudomonas sp. M18, an effective biocontrol agent, which is highly homologous to the opportunistic human pathogen P. aeruginosa PAO1, however little is known about the correlation between the expressions of two phz gene clusters. METHODOLOGY/PRINCIPAL FINDINGS: Two chromosomal insertion inactivated mutants for the two gene clusters were constructed respectively and the correlation between the expressions of two phz gene clusters was investigated in strain M18. Phenazine-1-carboxylic acid (PCA) molecules produced from phzA2-G2 gene cluster are able to auto-regulate expression itself and activate the expression of phzA1-G1 gene cluster in a circulated amplification pattern. However, the post-transcriptional expression of phzA1-G1 transcript was blocked principally through 5'-untranslated region (UTR). In contrast, the phzA2-G2 gene cluster was transcribed to a lesser extent and translated efficiently and was negatively regulated by the GacA signal transduction pathway, mainly at a post-transcriptional level. CONCLUSIONS/SIGNIFICANCE: A single molecule, PCA, produced in different quantities by the two phz gene clusters acted as the functional mediator and the two phz gene clusters developed a specific regulatory mechanism which acts through 5'-UTR to transfer a single, but complex bacterial signaling event in Pseudomonas sp. strain M18.

Abstract Background Cancer associated fibroblasts (CAFs) can remodel tumor microenvironment by secreting exosomes. This study aimed to investigate the role of exosomes derived from cancer-associated fibroblasts in colorectal cancer (CRC) progression. Methods Circular RNA (circRNA) array was used to identify differentially expressed circRNAs in exosomes from normal fibroblasts (NFs) and CAFs, and confirmed one differentially expressed circRNA circ_0067557 by real-time PCR. The effect of circ_0067557 on proliferation, metastasis, chemoresistance and apoptosis was verified by wound heal, tranwell, CCK8, sphere-forming and flow cytometry assay. Results Circ_0067557 expression in exosomes from CAFs was higher than those from NFs. CAF-derived exosomes promoted the proliferation, migration, invasion and chemoresistance of CRC cells while suppressed apoptosis. Silencing of circ_0067557 inhibited malignant phenotypes of CRC cells by targeting Lin28A and Lin28B. Moreover, CAF-derived exosomes enhanced the growth of CRC xenograft tumors. Conclusion Circ_0067557/Lin28A and Lin28B signal axis may be a potential therapy target for CRC.