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Recombinant Adeno-associated virus(rAAV) is currently the most widely used gene delivery vector and has been successfully used in various disease models, benefiting from its low immunogenicity, almost no toxicity, and no reported pathogenicity in humans. However, its low transduction efficiency for primary cells, especially for T lymphocytes, limits its further application in the field of cell therapy. In this study, we optimized the protocol for rAAV6 transduction of primary T cells, significantly improved the expression efficiency of the rAAV6 delivered CAR gene, and successfully generated rAAV6-based CAR-T cells (AAV-CAR-T). The gene expression intensity (mean fluorescence intensity, MFI) of rAAV6 transduced T cells treated with the tyrosine kinase inhibitor, Genistein, was increased 1–3-fold. Moreover, our results showed that rAAV6 efficiently transduced T cells stimulated with OKT3 and the gene expression could be enhanced 3-fold with an OKT3 concentration of 50 ng/mL in the medium. The gene expression intensity of T cells treated with OKT3 together with genistein could be augmented by 7-fold. Based on the above-optimized method, CAR-T cells prepared with rAAV6 showed evident anti-tumor ability both in vitro and in vivo. Our findings established an efficient method for the AAV transduction of T cells and would provide an alternative way for the preparation of CAR-T cells. [Display omitted] • Genistein can highly enhance rAAV-mediated gene expression in primary T cells. • OKT3 is necessary for rAAV-mediated efficient transduction of primary T cells. • OKT3 in combination with genistein can further enhance rAAV-mediated gene expression of primary T cells. • rAAV-CAR-T cells exhibit anti-tumor cell ability in vitro and in vivo. [ABSTRACT FROM AUTHOR]

• This is a fundamental research work which systematically studied the electrochemical behaviors of tantalum ion and its electrodeposition in molten salt. • The reduction and diffusion processes of tantalum ions in NaCl-KCl molten salt were determined. • Kinetic parameters, such as the diffusion coefficient, were investigated in detail and compared with previous work. • The nucleation mode of tantalum ions was studied, and a constant potential electrolysis was carried out to obtain metallic tantalum. This paper systematically studied the electrochemical behaviors of tantalum ions in NaCl-KCl molten salt, and pure metallic tantalum was collected on the cathode. Through a series of electrochemical methods such as cyclic voltammetry, square wave voltammetry, and chronopotentiometry, the reduction and diffusion processes of tantalum ions in NaCl-KCl molten salt were determined. The diffusion coefficient and nucleation mode of tantalum ions were investigated, and the electrodeposition was carried out at a certain potential. The results showed that the electrode reduction process of tantalum ion in NaCl-KCl molten salt at 1023 K is a two-step reaction Ta(V)→Ta(II)→Ta, and the reaction Ta(V)→Ta(II) was reversible and controlled by diffusion. The nucleation mode of tantalum ion was determined to be instantaneous nucleation by chronoamperometry. The cathode deposition product was analyzed by SEM, EDS and XRD, and it was confirmed that the deposition product was granular and the main component was tantalum. [Display omitted] [ABSTRACT FROM AUTHOR]

Polycyclodextrin (denoted PCD) composed of cyclodextrin monomer units and 1,3-diethoxypropan-2-ol containing many hydroxyl groups with lone pairs of electrons, easily coordinated with transition metals with empty orbitals. The CD unit can also provide host-guest binding sites for functional molecules. This article utilizes this feature of PCD for the first time as a "linker" to combine transition metal nanomaterials with synergistic functional molecules. We synthesized PCD with 50% CD monomer by epichlorohydrin cross-linking method. Utilizing the coordination effect of the hydroxyl group in PCD and the iron ion in photothermal nanoparticles (PB-Yb), the PCD is coated on its surface; simultaneously, CD in PCD can form a host-guest complex with adamantane-modified zinc phthalocyanine (Pc) photosensitizer. Using PCD as a "linker", PB-Yb and Pc (denoted PYPP) were combined to improve the solubility of PB-Yb, reduce the aggregation degree of Pc to increase their activity, and achieve photothermal and photodynamic synergistic tumor therapy. • Polycyclodextrin (PCD) with a cyclodextrin monomer content of 50% was synthesized. • PCD could be a linker to connect nanomaterials and active molecules. • The nanomedicine has an excellent synergistic tumor-suppression ability. • It is a first example of PCD as linker for multifunctional nanomedicine fabrication. [ABSTRACT FROM AUTHOR]

Abstract: Historical profiles and sources of PAHs at two typical sediment cores (i.e., the shipping route site and the shoal site) were fully compared to probe the controlling factors, specifically the water currents, for the PAHs deposition processes in the Yangtze River Estuary. Compared with ocean water currents, river runoff affected by the water impoundment of the Three Gorges Dam greatly affected the PAHs levels and percent contribution of PAHs sources in the two cores. River runoff hindered the PAHs deposition in shoal site, while a contrary phenomenon was observed for the shipping route site. Though the PAHs in the estuary were mainly from river catchment, only low ring PAHs in the shipping route site were mainly from the upper reach of the river. Coarse sediments with higher organic carbon content also accounted for the higher deposition levels of PAHs in the shipping route site. [Copyright &y& Elsevier]

Application of local anesthetic reagents, such as lidocaine (Lid), could cause significant neurotoxicity in spinal cord dorsal root ganglia neurons (DRGNs). In this study, we investigated the potential rescuing effect of cordycepin (CDC) in an in vitro explant model of lidocaine-induced apoptosis in DRGNs. Explant of rat neonatal DRGNs was prepared, and treated with Lid in vitro to induce neuronal apoptosis. Prior to Lid treatment, DRGN explant was pre-incubated with various concentrations of CDC to evaluate its rescuing effect on Lid-induced apoptosis. We found that, in cultured DRGNs, Lid caused significant neuronal apoptosis whereas pre-incubation of CDC rescued Lid-induced neurotoxicity. In addition, gene and protein expressions of Caspase-9 and Matrix metalloproteinase 3 (MMP3), a key component of inflammatory signal pathway, were both upregulated by Lid but downregulated by CDC pre-incubation. We further overexpressed MMP3 in cultured DRGNs. And discovered that forced MMP3 overexpression upregulated endogenous MMP3 and caspase-9, and reversed the rescuing effect of CDC on Lid-induced neurotoxicity in DRGNs. Therefore, we concluded that CDC has protective effect on local anesthesia induced spinal cord neurotoxicity, possibly through the inverse regulation on inflammatory signaling pathway. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) has been the third commonest cancer in the world. The prognosis of patients with CRC is related to the molecular subtypes and gene mutations, which is prone to recurrence, metastasis, and drug resistance. Mesenchymal stem cells (MSCs) are a group of progenitor ones with the capabilities of self-renewal， multi-directional differentiation, and tissue re-population, which could be isolated from various kinds of tissues and be differentiated into diverse cell types. In recent years, MSCs are applied for mechanisms study of tissue repairing, graft-versus-host disease (GVHD) and autoimmune-related disease, and tumor development, with the advantages of anti‐inflammation, multi-lineage differentiation, and homing capability. Integrating the chemotherapy and MSCs therapy might provide a novel treatment approach for CRC patients. In this review, we summarize the current progress in the integrated treatment of integrating the MSCs and chemotherapy for CRC. [Display omitted] • MSCs process tumor homing and immunomodulatory properties, providing new ideas for the anti-cancer therapies. • MSCs and their exosomes have shown the therapeutic roles in CRC. • Chemotherapeutic drugs and genes can be carried by MSCs to reduce the toxicity for CRC therapy. • The combination of MSCs and chemotherapy can decrease the drug resistance. [ABSTRACT FROM AUTHOR]

Highlights: [•] Chronological records of metal deposition at different estuarine sites were studied. [•] Sedimentary metal speciation reveal responses to upstream hydrological events. [•] The transformation of metal speciation can explain the intercepting role of dams. [•] Sediment particles and organic carbon are the proxies for the metals deposition. [Copyright &y& Elsevier]

Abstract: Batch leaching experiments, Freudlich isotherm, correlation analysis (CA) and principal component analysis (PCA) were undertaken to explore the mechanisms that govern the release of sediment–associated metals (i.e. Cd, Cu, Mn and Pb) under the salinity stress in the Yangtze River Estuary. Special attention has been paid to the role of sediments’ physico-chemical properties and metal chemical speciation. The increase of salinity promoted the metal mobility which followed the order: Cd>Mn>Cu>Pb. Sediments properties (e.g., particle component and organic carbon) governed the mobility of Cd; metal chemical speciation controlled the release of Mn, while the mobility of Cu and Pb were simultaneously affected by the two factors. Different metal release mechanisms caused by salinity changes might be explained by: the chloro-complexation for Cd, the encouragement of acidity changes for Mn, and the high affinity to Fe–Mn oxides, organic substances and specific sorption sites in the sediments for Cu and Pb. Under salinity effect, Cd and Mn exhibited higher ecological risk and mobility, while Cu and Pb seemed to be more conservative. [Copyright &y& Elsevier]

Abstract: Understanding the effect of postherpetic neuralgia (PHN) pain on brain activity is important for clinical strategies. This is the first study, to our knowledge, to relate PHN pain to small-world properties of brain functional networks. Functional magnetic resonance imaging (fMRI) was used to construct functional brain networks of the subjects during the resting state. Sixteen patients with PHN pain and 16 (8 males, 8 females for both groups) age-matched controls were studied. The PHN patients exhibited decreased local efficiency along with non-significant changes of global efficiency in comparison with the healthy controls. Moreover, regional nodal efficiency was found to be significantly affected by PHN pain in the areas related to sense (postcentral gyrus, inferior parietal gyrus and thalamus), memory/affective processes (parahippocampal gyrus) and emotional activities (putamen). Significant correlation (p <0.05) was also found between the nodal efficiency of putamen and pain intensity in PHN patients. Our results suggest that PHN modulates the local efficiency, and the small-world properties of brain networks may have potentials to objectively evaluate pain information in clinic. [Copyright &y& Elsevier]