Tumor-associated antigens (TAAs) have been tested in various clinical trials in cancer treatment but the patterns of specific T cell response to personalized TAA immunization remains to be fully ...understood. We report antigen-specific T cell responses in patients immunized with dendritic cell vaccines pulsed with personalized TAA panels. Tumor samples from patients were first analyzed to identify overexpressed TAAs. Autologous DCs were then transfected with pre-manufactured mRNAs encoding the full-length TAAs, overexpressed in the patients' tumors. Patients with glioblastoma multiforme (GBM) or advanced lung cancer received DC vaccines transfected with personalized TAA panels, in combination with low-dose cyclophosphamide, poly I:C, imiquimod and anti-PD-1 antibody. Antigen-specific T cell responses were measured. Safety and efficacy were evaluated. A total of ten patients were treated with DC vaccines transfected with personalized TAA panels containing 3–13 different TAAs. Among the seven patients tested for anti-TAA T cell responses, most of the TAAs induced antigen-specific CD4
+
and/or CD8
+
T cell responses, regardless of their expression levels in the tumor tissues. No Grade III/IV adverse events were observed among these patients. Furthermore, the treated patients were associated with favorable overall survival when compared to patients who received standard treatment in the same institution. Personalized TAA immunization-induced-specific CD4
+
and CD8
+
T cell responses without obvious autoimmune adverse events and was associated with favorable overall survival. These results support further studies on DC immunization with personalized TAA panels for combined immunotherapeutic regimens in solid tumor patients.
Trial registration
ClinicalTrials.gov, NCT02709616 (March, 2016), NCT02808364 (June 2016), NCT02808416 (June, 2016).
Chaos in nonlinear dynamical systems is featured with irregular appearance and with high sensitivity to initial conditions. Near-infrared light chaos based on semiconductor lasers has been ...extensively studied and has enabled various applications. Here, we report a fully-developed hyperchaos in the mid-infrared regime, which is produced from interband cascade lasers subject to the external optical feedback. Lyapunov spectrum analysis demonstrates that the chaos exhibits three positive Lyapunov exponents. Particularly, the chaotic signal covers a broad frequency range up to the GHz level, which is two to three orders of magnitude broader than existed mid-infrared chaos solutions. The interband cascade lasers produce either periodic oscillations or low-frequency fluctuations before bifurcating to hyperchaos. This hyperchaos source is valuable for developing long-reach secure optical communication links and remote chaotic Lidar systems, taking advantage of the high-transmission windows of the atmosphere in the mid-infrared regime.
Dendrite growth of alkali metal anodes limited their lifetime for charge/discharge cycling. Here, we report near-perfect anodes of lithium, sodium, and potassium metals achieved by electrochemical ...polishing, which removes microscopic defects and creates ultra-smooth ultra-thin solid-electrolyte interphase layers at metal surfaces for providing a homogeneous environment. Precise characterizations by AFM force probing with corroborative in-depth XPS profile analysis reveal that the ultra-smooth ultra-thin solid-electrolyte interphase can be designed to have alternating inorganic-rich and organic-rich/mixed multi-layered structure, which offers mechanical property of coupled rigidity and elasticity. The polished metal anodes exhibit significantly enhanced cycling stability, specifically the lithium anodes can cycle for over 200 times at a real current density of 2 mA cm
with 100% depth of discharge. Our work illustrates that an ultra-smooth ultra-thin solid-electrolyte interphase may be robust enough to suppress dendrite growth and thus serve as an initial layer for further improved protection of alkali metal anodes.
Drug therapy unavoidably brings toxic side effects and drug content-limited therapeutic efficacy although many nanocarriers have been developed to improve them to a certain extent. In this work, a ...concept of drug-free therapeutics is proposed and defined as a therapeutic methodology without the use of traditional toxic drugs, without the consumption of therapeutic agents during treatment but with the inexhaustible therapeutic capability to maximize the benefit of treatment, and a Z-scheme SnS
-WO
nanocatalyst is developed to achieve near infrared (NIR)-photocatalytic generation of oxidative holes and hydrogen molecules for realizing combined hole/hydrogen therapy by the drug-free therapeutic strategy. Without the need of any drug and other therapeutic agent assistance, the nanocatalyst oxidizes/consumes intratumoral over-expressed glutathione (GSH) by holes and simultaneously generates hydrogen molecules in a lasting and controllable way under NIR irradiation. Mechanistically, generated hydrogen molecules and GSH consumption inhibit cancer cell energy and destroy intratumoral redox balance, respectively, to synergistically damage DNA and induce tumor cell apoptosis. High efficacy and biosafety of combined hole/hydrogen therapy of tumors are achieved by the nanocatalyst. The proposed catalysis-based drug-free therapeutic strategy breaks a pathway to realize high efficacy and low toxicity of cancer treatment.
p-aminothiophenol (PATP) is an important molecule for surface-enhanced Raman spectroscopy (SERS). It can strongly interact with metallic SERS substrates and produce very strong SERS signals. It is a ...molecule that has often been used for mechanistic studies of the SERS mechanism as the photon-driven charge transfer (CT) mechanism is believed to be present for this molecule. Recently, a hot debate over the SERS behavior of PATP was triggered by our finding that PATP can be oxidatively transformed into 4,4'-dimercaptoazobenzene (DMAB), which gives a SERS spectra of so-called "b2 modes". In this perspective, we will give a general overview of the SERS mechanism and the current status of SERS studies on PATP. We will then demonstrate with our experimental and theoretical evidence that it is DMAB which contributes to the characteristic SERS behavior in the SERS spectra of PATP and analyze some important experimental phenomena in the framework of the surface reaction instead of the contribution "b2 modes". We will then point out the existing challenges of the present system. A clear understanding of the reaction mechanism for nitrobenzene or aromatic benzene will be important to not only understand the SERS mechanism but to also provide an economic way of producing azo dyes with a very high selectivity and conversion rate.
Polysaccharides are important components of Panax notoginseng that contribute to its immunomodulatory ability. This study aimed to isolate polysaccharides from notoginseng and investigate the ...structural feature and potential immunomodulatory activity.
The polysaccharide was isolated from notoginseng by anion exchange and gel permeation chromatography. Its preliminary structure was characterized by Fourier transform infrared (FT-IR) spectroscopy, gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance (NMR) spectroscopy. The immunoregulatory function was further investigated in cyclophosphamide induced immunosuppressive mice, murine splenocytes and macrophages.
A novel homogeneous polysaccharide (PNPB1) was isolated from notoginseng with the molecular weight of 9.3 × 10
Da. Monosaccharide composition analysis indicated that PNPB1 consisted of Glc (88.2%), Gal (9.0%), Ara (2.4%) and trace GlcA, with the major backbone of (1→4)-linked α-Glcp, (1→6)-linked β-Glcp, and (1, 4→6)-linked β-Glcp. The polysaccharide was found to significantly enhance murine body weight, improve their thymus and spleen indices and increase the white blood cells (WBC). PNPB1 significantly enhanced splenic lymphocyte proliferation, NO and cytokine (TNF-α, IL-2, IL-10 and IFN-γ) production, as well as the phagocytosis and TLR2 expression of peritoneal macrophages, indicating potent immunoenhancement effect.
These findings provide a theoretical basis for elucidating the structure and immune activity of notoginseng polysaccharides.
Enzymes constitute an extremely important class of biomacromolecules with diverse catalytic functions, which have been validated as key mediators for regulating cellular metabolism and maintaining ...homeostasis in living organisms ....
Taking advantage of the unique capacity of surface plasmon resonance, plasmon-enhanced heterogeneous catalysis has recently come into focus as a promising technique for high performance light-energy ...conversion. This work performs a theoretical study on the reaction mechanism for conversions of p-aminothiophenol (PATP) and p-nitrothiophenol (PNTP) to aromatic azo species, p,p′-dimercaptoazobenzene (DMAB). In the absence of O2 or H2, the plasmon-driven photocatalysis mechanism (hot electron–hole reactions) is the major reaction channel. In the presence of O2 or H2, the plasmon-assisted surface catalysis mechanism (activated oxygen/hydrogen reactions) is the major reaction channel. The present results show that the coupling reactions of PATP and PNTP strongly depend on the solution pH, the irradiation wavelength, the irradiation power, and the nature of metal substrates as well as the surrounding atmosphere. The present study has drawn a fundamental physical picture for understanding plasmon-enhanced heterogeneous catalysis.
•The solidification performance of four solidifying agents in fly ash were compared.•Their leachability were analyzed in accordance with different extraction procedures.•Solidifying agents with ...multiply hydrosulfide groups show excellent performance.•The leaching content of Cd, Ni, Pb and Zn is higher than the thresholds in China.•The excessive acetic acid makes its binding capacity stronger in HJ/T 300-2007.
Investigated in this paper were the content, specification distribution, and risk assessment code (RAC) determination of six targeted heavy metals and potentially toxic metals in fly ashes from a municipal solid waste incinerator in China. Contained in it is a comparison of the solidification/stabilization performance of two novel solidifying agents of sixthio guanidine acid (SGA) and tetrathio bicarbamic acid (TBA) with sodium dimethyldithiocarbamate (SDD) and Na2S, and analysis of their leachability in accordance with TCLP 1311 of the US EPA and the extraction procedures of China (HJ/T 299-2007 and HJ/T300-2007). The total concentration of Zn, Cu, Ni, Pb, Cr, Cd is 37383.47, 3080.77, 1583.92, 1356.43, 566.15, and 77.83mg/kg, respectively. Cr (3.7%) and Pb (7.50%) pose low risk; and Ni (12.93%) and Zn (15.45%) have a medium risk; while Cu (69.84%) and Cd (82.5%) have a very high risk according to their RAC score. Compared with SDD and Na2S, SGA and TBA show an excellent overall solidifying performance due to their multiply hydrosulfide groups that bind with heavy metals very efficiently. The obtained results indicate that the leaching content of Cd, Ni, Pb and Zn is higher than the thresholds prescribed in GB5085.3-2007, and the excessive acetic acid makes its binding capacity stronger in HJ/T 300-2007 than in TCLP 1311.
The mechanism by which nutrient status regulates the fusion of autophagosomes with endosomes/lysosomes is poorly understood. Here, we report that O-linked β-N-acetylglucosamine (O-GlcNAc) transferase ...(OGT) mediates O-GlcNAcylation of the SNARE protein SNAP-29 and regulates autophagy in a nutrient-dependent manner. In mammalian cells, OGT knockdown, or mutating the O-GlcNAc sites in SNAP-29, promotes the formation of a SNAP-29-containing SNARE complex, increases fusion between autophagosomes and endosomes/lysosomes, and promotes autophagic flux. In Caenorhabditis elegans, depletion of ogt-1 has a similar effect on autophagy; moreover, expression of an O-GlcNAc-defective SNAP-29 mutant facilitates autophagic degradation of protein aggregates. O-GlcNAcylated SNAP-29 levels are reduced during starvation in mammalian cells and in C. elegans. Our study reveals a mechanism by which O-GlcNAc-modification integrates nutrient status with autophagosome maturation.
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