Platelet Parameters, C-Reactive Protein, and Depression: An Association Study.

OBJECTIVE: This study aims to investigate the correlation of platelet parameters and C-reactive protein (CRP) with depression. METHODS: The clinical data of 61 patients with depression and 30 healthy control subjects were collected to compare the platelet parameters, CRP levels, and Hamilton Depression Rating Scale (HAMD) scores of the two groups for correlation analysis. RESULTS: The results revealed that the body mass index (BMI) of patients with depression was lower (P < 0.05) than that of the healthy control subjects, and that this difference was more significant in women than in men. Patients with severe depression showed an increased mean platelet volume (MPV) (P < 0.05). In the patients with depression, MPV was positively correlated (P < 0.05) with HAMD scores for work and interest, gastrointestinal symptoms, hopelessness, the anxiety/somatization factor, and the hopelessness factor. Platelet count (PLT) was negatively correlated (P < 0.05) with HAMD scores for hypochondriasis, and plateletcrit (PCT) was negatively correlated (P < 0.05) with HAMD scores for middle insomnia and hypochondriasis. Platelet distribution width (PDW) was positively correlated (P < 0.05) with HAMD scores for gastrointestinal and systemic symptoms as well as hopelessness. Higher CRP levels (P < 0.05) were found in the patients with depression than in the healthy control subjects. Furthermore, in the patients with depression, CRP levels were positively correlated (P < 0.05) with HAMD scores for guilt and the cognitive impairment factor. CONCLUSION: Classical platelet parameters (PLT, MPV, PCT, PDW) and CRP were shown to be associated with specific depressive symptoms and cognitive impairment factors, including sleep, gastrointestinal symptoms, hypochondriasis, losing interest in work, and despair. These results suggest that both platelet parameters and CRP could be suitable biomarkers for predicting the occurrence and prognosis of depression, thus providing a new target for its treatment.

The role of angiotensin-(1-7) on acquired platinum resistance-induced angiogenesis in non-small cell lung cancer in vitro and in vivo.

Renin-angiotensin system (RAS) signaling has been implicated in the development of cancer. The new RAS ACE2/Ang-(1-7)/Mas axis antagonizes the classical ACE/Ang II/AT1R axis. Ang-(1-7) has pleiotropic roles in lung cancer including suppressing proliferation, angiogenesis, and metastasis. This research was designed to investigate the effect of Ang-(1-7) on tumor-associated angiogenesis in DDP-resistant lung cancer cell lines. We first established acquired DDP-resistant cell lines A549 (A549-DDP) and LLC (LLC-DDP). We next performed RT-qPCR, western blot, ELISA, tube formation, microvessel density detection, immunohistochemistry, and tumor formation assays. The results showed that the mRNA and protein levels of RAS components and vascular endothelial growth factor A (VEGFa) were lessened in the A549/LLC-DDP+Ang-(1-7) group compared with the A549/LLC-DDP group. This effect could be blocked by the MAS receptor antagonist A779. The data revealed that Ang-(1-7) could perform its antiangiogenic function by PI3K/AKT and MAPK pathways. Furthermore, the impact of Ang-(1-7) on tumor-associated angiogenesis has been confirmed in lung cancer xenograft model with acquired DDP resistance. These results provide a theoretical basis for designing therapeutic strategies for targeting Ang-(1-7) in the treatment of NSCLC.

Gram-scale synthesis of a neodymium chelate as a spectral CT and second near-infrared window imaging agent for visualizing the gastrointestinal tract in vivo.

The diagnosis of gastrointestinal (GI) tract diseases is frequently performed in the clinic, so it is crucial to develop high-performance contrast agents for real-time and non-invasive imaging examination of the GI tract. Herein, we show a novel method to synthesize a neodymium (Nd) chelate, Nd-diethylenetriaminepentaacetic acid (Nd-DTPA), on a large scale without byproducts for spectral computed tomography (CT) and second near-infrared window imaging of the GI tract in vivo. The Nd-DTPA was simply generated by heating the mixture of Nd2O3 and DTPA in water at 85 °C for 2 h. This dual-modal imaging agent has the advantages of a simple and green synthesis route, no need of purification process, high yield (86.24%), large-scale production capability (>10 g in lab synthesis), good chemical stability and excellent water solubility (≈2 g mL-1). Moreover, the Nd-DTPA emitted strong near-infrared fluorescence at 1308 nm, and exhibited superior X-ray attenuation ability compared to clinical iohexol. The proposed Nd-DTPA can integrate the complementary merits of dual-modal imaging to realize spatial-temporal and highly sensitive imaging of the GI tract in vivo, and accurate diagnosis of the location of intestinal obstruction and monitor its recovery after surgery. The developed highly efficient method for the gram-scale synthesis of Nd-DTPA and the proposed spectral CT and second near-infrared window dual-modal imaging strategy provide a promising route for accurate visualization of the GI tract in vivo.

Rhenium Sulfide Nanoparticles as a Biosafe Spectral CT Contrast Agent for Gastrointestinal Tract Imaging and Tumor Theranostics in Vivo.

Spectral computed tomography (CT) imaging as a novel imaging technique shows promising prospects in the accurate diagnosis of various diseases. However, clinically iodinated contrast agents suffer from poor signal-to-noise ratio, and emerging heavy-metal-based CT contrast agents arouse great biosafety concern. Herein, we show the fabrication of rhenium sulfide (ReS2) nanoparticles, a clinic radiotherapy sensitizer, as a biosafe spectral CT contrast agent for the gastrointestinal tract imaging and tumor theranostics in vivo by teaching old drugs new tricks. The ReS2 nanoparticles were fabricated in a one-pot facile method at room temperature, and exhibited sub-10 nm size, favorable monodispersity, admirable aqueous solubility, and strong X-ray attenuation capability. More importantly, the proposed nanoparticles possess an outstanding spectral CT imaging ability and undoubted biosafety as a clinic therapeutic agent. Besides, the ReS2 nanoparticles possess appealing photothermal performance due to their intense near-infrared absorption. The proposed nano-agent not only guarantees obvious contrast enhancement in gastrointestinal tract spectral CT imaging in vivo, but also allows effective CT imaging-guided tumor photothermal therapy. The proposed "teaching old drugs new tricks" strategy shortens the time and cuts the cost required for clinical application of nano-agents based on existing clinical toxicology testing and trial results, and lays down a low-cost, time-saving, and energy-saving method for the development of multifunctional nano-agents toward clinical applications.

Turning solid into gel for high-efficient persistent luminescence-sensitized photodynamic therapy.

Bioavailable persistent luminescence material is an ideal internal light source for long-term photodynamic therapy, but inevitably suffers from low utilization efficiency and weak persistent luminescence due to corrosion and screening processes. Herein, we show a facile and smart "turning solid into gel" strategy to fabricate persistent luminescence hydrogel for high-efficient persistent luminescence-sensitized photodynamic therapy. The homogeneous persistent luminescence hydrogel was synthesized via dispersing high-temperature calcined persistent luminescence material without corrosion and screening into a biocompatible alginate-Ca2+ hydrogel. The simple synthesis strategy allows 100% of utilization efficiency and intact persistent luminescence of persistent luminescence material. The persistent luminescence hydrogel possesses favorable biocompatibility, bright persistent luminescence, red light renewability, good syringeability, and strong fixing ability in tumors. The persistent luminescence hydrogel can be easily injected in vivo as a powerful localized light source for superior persistent luminescence-sensitized photodynamic therapy of tumors. The "turning solid into gel" strategy enables taking full advantages of persistent luminescence for biological applications, and shows great potential in utilizing diverse theranostic agents regardless of hydrophilicity and hydrophobicity.

Biocompatible Iodine-Starch-Alginate Hydrogel for Tumor Photothermal Therapy.

Photothermal therapy (PTT) with the advantages of high efficiency and minimal invasiveness is a promising technique for tumor therapy, but clinical application of PTT agents has been stifled by the great safety concerns. Herein, a deep blue iodine-starch-alginate (ALG) hydrogel is elegantly fabricated based on the classic and simple "iodine-starch test" for in vivo tumor PTT in a facile and mild way. The iodine-starch-ALG hydrogel composed of clinically used agents is fabricated by dispersing blue iodine-starch complex into alginate-Ca2+ hydrogel, which guarantees the good chemical stability of iodine-starch complex via separating them from surrounding reductive environment. The iodine-starch-ALG hydrogel possesses favorable biocompatibility derived from the biosafe and degradable components and possesses good photothermal heating ability based on iodine-starch chromophore. The proposed iodine-starch-ALG hydrogel is successfully applied in tumor PTT in vitro and in vivo for the first time. This work lays down a novel way for the development of high-performance and biocompatible biomaterials via teaching old drugs new tricks.

Molecular dynamics simulation of electric-field-induced self-assembly of diblock copolymers.

The self-assembly of block copolymers under an external electric field was studied with a coarse-grained polarizable model that hybridizes the conventional polymeric coarse-grained model and Drude oscillator. The polarizability of the coarse-grained polymeric segment was reflected by the Drude oscillator. Applying this model, the alignment of the lamellar phase of the block copolymer melt under an external electric field was observed and the dynamic coupling information between chain polarization and interface orientation induced by the external electric field was obtained. It is demonstrated that the alignment of the lamellar structure along the electric field direction results from the polarizability difference of the polymer components. Finally, the transitions of phase structures of the block copolymer under an external electric field, from spherical phase to cylindrical phase, from gyroid structure to cylindrical phase, and from gyroid structure to lamellae phase were simulated. The specific evolution pathways were shown.

Tuning phase structures of a symmetrical diblock copolymer with a patterned electric field.

Electric fields can induce the orientation of the phase interfaces of block copolymers and provide a potential method to tune polymer phase structures for nanomaterial manufacture. In this work, we applied self-consistent field theory to study the self-assembly of a diblock copolymer confined between two parallel neutral substrates on which a set of electrodes was imposed to form a patterned electric field. The results showed that an alternatively distributed electric field can induce the formation of a parallel lamellar phase structure, which exists stably only in the system with selective substrates. The phase structure was proved to be sensitive to the characteristics of the electric field distribution, such as the strength of the electric field, the size and position of the electrodes, and the corresponding phase diagram was calculated in detail. The transition pathway of the phase structure from the perpendicular layered phase to the parallel layered phase was further analysed using the minimum energy path method. It is shown that the path and the active energy barrier of the phase transition depend on the electric field strength. Compound electric field patterns that can be designed to control the formation of novel and complex microphase structures were also examined.

Self-assembly of diblock copolymer confined in an array-structure space.

The combination of top-down and bottom-up technologies is an effective method to create the novel nanostructures with long range order in the field of advanced materials manufacture. In this work, we employed a polymeric self-consistent field theory to investigate the pattern formation of diblock copolymer in a 2D confinement system designed by filling pillar arrays with various 2D shapes such as squares, rectangles, and triangles. Our simulation shows that in such confinement system, the microphase structure of diblock copolymer strongly depends on the pitch, shape, size, and rotation of the pillar as well as the surface field of confinement. The array structures can not only induce the formation of new phase patterns but also control the location and orientation of pattern structures. Finally, several methods to tune the commensuration and frustration of array-structure confinement are proposed and examined.

Alterations of dendritic cells, inflammatory monocytes and macrophages in mice during Pneumocystis ;murina infection / 中华微生物学和免疫学杂志

Objective To investigate the alterations and phenotypes of dendritic cells, inflamma-tory monocytes and macrophages in immunocompetent mice during Pneumocystis murina ( P.murina) infec-tion for further analysis of the function of these cells during P.murina infection.Methods Wild type male C57BL/6 mice at age 6-8 weeks were randomly divided into two groups including the group with P.murina infection and the group receiving sham surgery.The mice without any intervention were used to set up the blank control group.The loads of P.murina strains in lung tissues of each mouse were quantified by TaqMan real-time fluorescence polymerase chain reaction after the infection.Histopathological examination was per-formed to evaluate the degree of inflammation in lung tissues.The numbers of dendritic cells, inflammatory monocytes and macrophages in lung tissues, peripheral blood and bone marrow samples, and the changes of inflammatory monocytes in spleen tissues were measured by flow cytometry analysis.The expression of major histocompatability complexⅡ(MHCⅡ), CX3C chemokine receptor 1 (CX3CR1) and CC chemokine re-ceptor 2 ( CCR2 ) by dendritic cells, inflammatory monocytes and macrophages in lung tissues during P.murina infection were analyzed by flow cytometry analysis.All of the data were collected one, two, three and four weeks after the corresponding treatments.Results The loads of P.murina strains in P.murina in-fected mice were elevated after two and three weeks infection, but decline at week 4 (P>0.05).Significant pathological changes including the alveolar destruction, inflammatory cell infiltration and thickened alveolar septum in mice with P.murina infection were observed under a microscope at week 3 and week 4.Compared to the sham surgery treatment group, the number of CD11c+CD11b+dendritic cells were increased in lung tissues, but decreased in blood samples during P.murina infection ( P0.05).The CD11c+CD11b+dendritic cells in lung tissues of mice with P.murina infection expressed high levels of MHCⅡand CX3CR1, and low levels of CCR2.The inflammatory monocytes in lung tissues of mice expressed high levels of CCR2, moderate levels of MHCⅡand low levels of CX3CR1 during P.murina in-fection.High levels of CX3CR1 and low levels of MHCⅡ and CCR2 were observed in macrophages from lung tissues of mice with P.murina infection.Conclusion Highly expressed CD11c+CD11b+dendritic cells and MHCⅡwere detected in lung tissues of mice during P.murina infection, indicating that CD11c+CD11b+dendritic cells were involved in the host defense against P.murina infection.