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In this paper, AACGS concrete was prepared by using raw and 700 °C calcined coal gangue as the coarse aggregate and alkali-activated coal gangue-slag (AACGS) as the cementitious material. The variation of compressive strength and durability of AACGS concrete was studied, and the durability damage mechanism of AACGS concrete is analyzed in depth by SEM. The research results showed that coal gangue as coarse aggregate shows high compressive strength and good durability in AACGS concrete. AACGS concrete with calcined CGCA shows great advantages in compressive strength and sulfate attack resistance. Under the condition of large content, its long-term frost resistance durability and chloride ion permeability resistance are not as good as that of raw CGCA. If AACGS concrete is applied to the freeze-thaw environment, the content range of CGCA should be 30%–50%. This study provides an experimental basis for the large-scale utilization of coal gangue.

Cadmium (Cd) is a widely prevalent environmental pollutant that accumulates in the liver and induces liver injury. The mechanism of Cd-induced liver injury remains elusive. Our study aimed to clarify the mechanism by which changes in the gut microbiota contribute to Cd-induced liver injury. Here, a murine model of liver injury induced by chronic Cd exposure was used. Liver injury was assessed by biochemistry and histopathology. Expression profiles of genes involved in bile acid (BA) homeostasis, inflammation and injury were assessed via Realtime-PCR and Western-blot. 16S rRNA gene sequencing and mass spectrometry-based metabolomics were used to investigate changes in the gut microbiota and its metabolites in the regulation of Cd-induced liver injury. Here, we showed that Cd exposure induced hepatic ductular proliferation, hepatocellular damage and inflammatory infiltration in mice. Cd exposure induced gut microbiota dysbiosis and reduced the fecal bile salt hydrolase activity leading to an increase of tauro-β-muricholic acid levels in the intestine. Cd exposure decreased intestine FXR/FGF-15 signaling and promoted hepatic BA synthesis. Furthermore, the mice receiving fecal microbiota transplantation from Cd-treated mice showed reduced intestinal FXR/FGF-15 signaling, increased hepatic BA synthesis, and liver injury. However, the depletion of the commensal microbiota by antibiotics failed to change these indices in Cd-treated mice. Finally, the administration of the intestine-restricted FXR agonist fexaramine attenuated the liver injury, improved the intestinal barrier, and decreased hepatic BA synthesis in the Cd-treated mice. Our study identified a new mechanism of Cd-induced liver injury. Cd-induced gut microbiota dysbiosis, decreased feces BSH activity, and increased intestinal T-βMCA levels led to an inhibition of intestinal FXR/FGF-15 signaling and an increase in hepatic BA synthesis, ultimately facilitating the development of hepatic ductular proliferation, inflammation, and injury in mice. This study expands our understanding of the health hazards caused by environmental Cd pollution.

Benzene is a pollutant that widely exists in the environment and in occupational workplaces. Its exposure is closely associated with hematological disorders and even leukemia, which poses a significant threat to public health. Thus, the underlying mechanisms should be explored. In the current study, it was investigated whether ferroptosis plays a role in benzene hematopoietic toxicity and related mechanisms. Mice were subcutaneously injected with benzene at 150 mg/kg b.w. to establish a hematotoxicity model. Four weeks later, the mice exposed to benzene exhibited a decrease in white blood cells, red blood cells, and hemoglobin level, as well as reduction in frequency of hematopoietic stem and progenitor cells (HS/PCs) and the colony forming abilities of CFU-G, CFU-M, CFU-GM, and CFU-GEMM. Simultaneously, apart from ferroptosis features in the mitochondrial morphology, decreased ATP and mitochondrial membrane potential, alterations in biochemical indices and gene expression were also observed, such as increased intracellular iron and lipid peroxidation, glutathione (GSH) depletion, and reduced glutathione peroxidase (GSH-Px) level, and upregulated PTGS2. Meanwhile, markedly altered expression of SLC7A11, GPX4, GCLC, NOX1, TFRC, FTH1, and FTL hinted that redox imbalance and dysfunction of iron uptake and storage are vital to induce ferroptosis. Additionally, decreased cytoplasmic NRF2 and increased nuclear NRF2 were also found, suggesting the activation of the NRF2 pathway. More importantly, inhibition of ferroptosis with ferrostatin-1 (Fer-1) or deferoxamine (DFO) partially relieved the hematopoietic injuries. Our findings imply that dysregulation in the system Xc

A novel ion-imprinted blend membrane was fabricated to separate selectively platinum(IV) from aqueous media. An amphiphilic copolymer poly(methyl methacrylate)-b-poly(4-vinylpyridine) (PMMA-b-P4VP) was firstly synthesized via the reversible addition fragmentation chain transfer polymerization, and characterized by 1H NMR, FT-IR and GPC. Subsequently, poly(vinylidene fluoride) (PVDF) blend membranes were prepared using PMMA-b-P4VP as a blending additive. Effects of the following factors on performance of blend membranes were systematically examined: P4VP content of PMMA-b-P4VP, solvent type, and PMMA-b-P4VP/PVDF ratio. Further, platinum(IV) ion-imprinted membrane (Pt(IV)-IIM) was fabricated by blending polymer-Pt(IV) complexes with PVDF. SEM, FTIR-ATR, contact angle, water flux and adsorption capacity were employed to characterize all membranes. Results indicated that the membrane, which was prepared using the copolymer with high P4VP content (polymerization time 10 h) as a functional polymer, N,N-dimethylacetamide as a solvent and PMMA-b-P4VP/PVDF ratio of 30 wt%, exhibited an intriguing morphology and much higher performance. Pt(IV)-IIM showed higher adsorption and selectivity for Pt(IV) (selectivity coefficients of 27.66 ± 1.38 and 77.16 ± 3.86 for Pt(IV)/Cu(II) and Pt(IV)/Ni(II), respectively) compared with a non-imprinted membrane. During membrane filtration, Pt(IV)-IIM was effective and selective for separation of Pt(IV) in the presence of Cu(II) and Ni(II) ions. Also, Pt(IV)-IIM was chemical stable, and had a good regeneration performance.

The present paper discusses the adsorption and inhibitory effect of nitrogen-containing compound, 1-dodecyl-3-methyimidazolium chloride (DMIC), dodecylpyridinium chloride (DPC) and hexadecylpyridinium chloride monohydrate (HDPC) on Q235 steel corrosion in a new system（10 mol·L−1 methanol/0.1 mol·L−1 formic acid medium. The experimental study was carried out using a series of techniques such as weight loss, potentiodynamic polarization (PDP) and electrochemical impedance spectroscopy (EIS). contact angle test, Raman spectra, X-ray photoelectron spectroscopy (XPS) and atomic force microscope (AFM) served to identify microscopic variation on Fe surface. Adsorption isotherm model controlling the adsorption process are calculated and discussed. Moreover, the relationships between molecular structure and corrosion inhibition performance of three inhibitors were verified by quantum chemical calculation and molecular dynamics simulation. The results obtained from the electrochemical methods showed that DMIC, DPC and HDPC imparted high resistance and behaved as mixed-type corrosion inhibitors dominated with anode. inhibition efficiency (η%) increased with the increase of inhibitors concentration to attained 88.81%, 92.69%, 93.67% at 0.06 mol·L−1, respectively. Surface studies confirmed the existence of an adsorption film on the metal surface. The obtained results demonstrated that the adsorption process on the metal surface followed the Langmuir adsorption model. Quantum chemical calculations and molecular dynamics simulation (MD) testified the effect of the chemical structure of three inhibitors on its inhibition efficiency, which had a good agreement with the experimental data.

To enhance the corrosion resistance of AA2024-T3 in 0.01 mol·L−1 NaOH aqueous solution, the inhibition characteristics of the amphoteric surfactant disodium-N-dodecyliminodiacetate (RNC-12) were assessed by means of the static weight loss method, electrochemical impedance spectroscopy, potentiodynamic polarisation curves, atomic force microscopy and X-ray photoelectron spectroscopy, and the results were compared with those of sodium laurate (SL). Quantum chemical calculations and molecular dynamics (MD) simulations were also performed to predict and analyse the relationships between the molecular structure and inhibition efficiency. The results of the experiments revealed that RNC-12 achieved a higher inhibition efficiency of 91% as a valid inhibitor of AA2024-T3 in alkaline medium compared with SL (81%). The results of surface analysis showed that the two inhibitors could be well adsorbed on the alloy surface, and the degree of surface corrosion was as follows: without inhibitor >SL >RNC-12. Quantum chemical calculations and MD simulations showed that the anionic state of RNC-12 possesses a smaller band gap, larger dipole moment, and more negative energy of adsorption, indicating that RNC-12 is more easily adsorbed on the alloy surface than SL. Therefore, the experimental results were in accordance with the theoretical calculations.

To enhance the corrosion resistance of AA2024-T3 in aqueous NaOH (0.01 mol·L−1), the inhibition characteristics of the synthetic rosin-based anionic surfactant, 6-dehydroabietic acylamino sodium (6-DAS), were assessed using the static weight loss method, electrochemical impedance spectroscopy, potentiodynamic polarization curves, scanning electron microscopy, atomic force microscopy, X-ray photoelectron spectroscopy, UV–vis spectroscopy, and adsorption isotherm analysis. Simultaneously, quantum chemical calculations and molecular dynamics (MD) simulations were performed to predict and analyze the relationships between the molecular structure and inhibition efficiency. The results of the experiments revealed that 6-DAS achieved an inhibition efficiency of 92.95% as a valid corrosion inhibitor for AA2024-T3 in alkaline medium. Quantum chemical calculations showed that the anionic state of 6-DAS possessed a smaller band gap and a larger dipole moment than the neutral state, which indicated that anionic 6-DAS was easily adsorbed on the alloy surface in solution. This result was further proved by MD simulations, thereby strengthening the agreement between experimental results and theoretical calculations.

Surface sediment samples were collected from upstream down to the subaqueous delta of the Red River in Vietnam to assess heavy metal pollution. Sediment Cr and V concentrations are strongly correlated with Al, Fe, Mn and total organic carbon concentrations, as well as particle size, suggesting that these two metals are derived primarily from natural sources and enriched in the fine fraction of sediments. In contrast, Cu, Cd, Pb, Ni and Zn concentrations show weaker correlations with particle size, with very high concentrations observed at several sites in the upper reach of the river, pointing to anthropogenic input as a possible source of these heavy metals. Enrichment factors (EF) of Cu, Cd, Pb, Ni and Zn suggest that heavy metal pollution is present in sediments with significantly high values in the upstream. The data analysis indicates that Cd, Cu and Pb are the dominant pollutants in the Red River, with their concentrations reaching moderate to serious pollution levels.

Brookite TiO2 quasi nanocubes (BTN) decorated with various Cu nanoclusters (Cu NCs) contents (hereafter referred to as Cu/BTN composite) were synthesized via a facile chemical reduction process by NaBH4. The obtained products and its Cu's existential state were characterized by X-ray diffraction, UV–Vis diffuse reflectance absorption spectroscopy, electron microscopy, X-ray photoelectron spectroscopy and X-ray fluorescence spectroscopy. It was found that the introduction of Cu NCs with small size of ∼1–2 nm on BTN surfaces can improve the photocatalytic H2 production activity, and the maximum photoactivity (225 μmol h−1) for H2 production over 1.0 mol% Cu/BTN composite is similar to that (220 μmol h−1) of the benchmark photocatalyst (P25) under the optimum photoreaction conditions, which is 5.2 times higher than that (42.5 μmol h−1) of the BTN alone. This significant enhancement in the photoactivity of BTN is deemed to result from the metallic Cu NCs with high surface area and dispersion, which favour the co-catalyst functions to cause an effective photogenerated carrier separation in space and an improvement in the photocatalytic activity and stability for H2 production. The present results not only demonstrate the brookite TiO2 would be a potential effective photocatalyst for H2 production, but also provide an inexpensive, efficient and stable means of enhancing light-to-hydrogen energy conversion by using metallic Cu nanoclusters alternative to the commonly used noble metal co-catalyst.

The agglomerate microstructure determines the performance of the agglomerates in heap leaching. However, a detailed analysis of the agglomerate microstructure is still highly desirable. The purpose of this paper is to conduct a comprehensive analysis of the agglomerate microstructure to guide the agglomeration process. In this work, the microstructure of agglomerates prepared by geopolymerization was studied in detail. Besides, the effect of the agglomerate microstructure on leaching was verified by column bioleaching tests. Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR) tests indicated that geopolymer gel mainly bound the particles in agglomerates prepared by geopolymerization, and X-ray diffraction (XRD) and energy dispersive spectra (EDS) tests showed that the aluminosilicate in the ore hardly participated in geopolymerization. X-ray microtomography (XMT) test showed that there were many pores and cracks between particles in the agglomerates prepared by geopolymerization. The column bioleaching tests revealed that the agglomerates were quite stable, and the permeability and copper extraction of the agglomerates were still higher than that of the ore with the same particle size distribution. These results demonstrated that the agglomerates prepared by geopolymerization had a microstructure suitable for heap leaching.

The corrosion inhibition performances of Triton X-100 (TX-100), sodium silicate (Na2SiO3) and their mixture for aluminum alloy in 0.01 mol·L−1 NaOH solution were investigated by weight loss methods, electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization tests, scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS) and Fourier transform infrared (FTIR). The corrosion inhibition mechanism was explored by quantum chemical calculation and molecular dynamics simulation. From the results of tests, it was shown that the inhibition efficiency of TX-100 was about 44.03 % at concentration of 0.01 mol·L−1. And the inhibition efficiency reached about 85.84% when the mixture of TX-100 and Na2SiO3 at the same concentration 0.005 mol·L−1. The inhibition efficiency of Na2SiO3 was 97.23 % at 0.01 mol·L−1 due to the coating formation by higher aggregates silicates, which was different from mechanism of traditional inhibitor. Quantum chemical calculations manifested that SiO32− had a smaller energy gap (ΔE) than TX-100. The adsorption energy results of molecular dynamics simulation were consistent with the experimental results. The corrosion inhibition mechanism of the protective layers was also discussed by experimental methods and verified by theoretical research.

A three-component magnetic material, namely, Fe3O4@SiO2@CaSiO3, which featuring an Fe3O4@SiO2 core and a layered porous CaSiO3 shell, was synthesized via precipitation and utilized as an adsorbent to remove Ag+ from wastewater. The structure, morphology, composition, and magnetic properties of this material were analyzed by a series of characterization techniques, and its adsorption efficiency, adsorption thermodynamics, kinetic characteristics, and recyclability were investigated in detail. The magnetic Fe3O4@SiO2@CaSiO3 composite possessed a core–shell structure, with a cotton-like morphology, a specific surface area of 75.97 m2·g−1, pore size of 11.4 nm, pore volume of 0.36 cm3·g−1, and magnetization saturation of 60.5 emu·g−1. The adsorption equilibrium data of Ag+ adsorption by Fe3O4@SiO2@CaSiO3 fitted the Redlich–Peterson model well, and the equilibrium adsorption capacity of the material for Ag+ reached 127.84 mg·g−1 at an initial concentration of 225 mg·L−1 and temperature of 293 K. Kinteic studies showed that the adsorption process conformed well to the pseudo-second-order model and reached equilibrium within 150 min. The adsorption process was endothermic, with an activation energy of 8.475 kJ·mol−1 and accompanied by Ag O bonding and Ca2+ release. Therefore, the adsorption mechanism involved in Ag+ removal includes not only physisorption and ion exchange but also chemisorption, which is controlled by surface OH and O groups. The percentage of Ag+ removal tended to stabilize after five cycles of Fe3O4@SiO2@CaSiO3 reuse and but decreased by only 14.34%. Synthesized Fe3O4@SiO2@CaSiO3 exhibited excellent adsorption, regeneration, and magnetic separation performance. Thus, the synthesized Fe3O4@SiO2@CaSiO3 may potentially be applied to remove Ag+.

We address the problem of providing shared-path protection for a set of connection requests in a flexible bandwidth optical network under the constraint that the joint failure probability of the primary path and backup path of each request is below a given maximum joint failure probability threshold. The overall objective of the problem is to minimize spectrum consumption while meeting the maximum joint failure probability requirements. We propose the minimum free spectrum–block consumption algorithm (MFSB) for providing shared-path protection with joint failure probability requirements in flexible bandwidth optical networks, and we introduce two additional algorithms, named the conventional shared spectrum–block (CSSB) consumption algorithm and the maximum shared spectrum–block (MSSB) consumption algorithm, for comparison. Simulation results show that MFSB not only achieves better performance in terms of blocking probability, spectrum consumption, spectrum redundancy, and hop counts compared to the CSSB and MSSB algorithms, but also guarantees a joint failure probability that is lower than the MSSB algorithm. Furthermore, the spectrum efficiency of these three algorithms increases with the growth of the maximum shared degree, especially for the MFSB algorithm. Therefore, the MFSB algorithm provides a better tradeoff between the minimum spectrum–block consumption and the average joint failure probability.

Hepatocyte growth factor activator inhibitor type 2 (SPINT2), a Kunitz-type serine proteinase inhibitor, has been identified as a putative tumor suppressor gene silenced by promoter methylation. We aimed to investigate whether SPINT2 might act as an esophageal squamous cell carcinoma (ESCC) tumor suppressor gene. Four ESCC cell lines, Fifty-two ESCC tissues and twenty-nine neighboring non-cancerous tissues were included in this study. The expression of SPINT2 was monitored by real time PCR. Bisulfite genomic sequencing and methylation-specific PCR were used to analyze methylation status. The effect of SPINT2 on cell proliferation and apoptosis in EC109 and EC9706 cells was observed by CCK-8 assay and flow cytometric analysis. We found that silencing of SPINT2 was associated with promoter methylation in ESCC cell lines. The densely methylated SPINT2 promoter region was confirmed by bisulfite genomic sequencing. Ectopic expression of SPINT2 inhibited cell proliferation through inducing cell apoptosis in vitro. Furthermore, methylation-specific PCR analysis revealed that SPINT2 promoter methylation was prominent in carcinoma tissues (52.08%) compared with neighboring non-cancerous tissues (22.58%). Kaplan-Meier analysis showed that patients with SPINT2 hypermethylation had shorter survival time. The tumor suppressor gene of SPINT2 is commonly silenced by promoter hypermethylation in human ESCC and SPINT2 hypermethylation is correlated with poor overall survival, implicating SPINT2 is an underlying prognostic marker for human ESCC.

It is well known that different crystal facets of TiO2 have different surface electronic and atomic structures, which can influence the photocatalytic performance, and appropriate noble metal-loading usually improves the photocatalytic activity. Herein we demonstrate that Pt-loading can reverse the photocatalytic activity order of anatase TiO2 {0 0 1} facets (TiO2-0 0 1) and {0 1 0} facets (TiO2-0 1 0) for the photoreduction of CO2 to CH4. This new phenomenon was discussed on the bases of the experimental data including attenuated total reflectance Fourier transform infrared (ATR-IR) spectra, CO2 temperature programmed desorption (CO2-TPD) curves, transmission electron microscopy (TEM) images and time-resolved photoluminescence (PL) spectra. It is found that the higher photocatalytic CO2 reduction activity of TiO2-0 1 0 without Pt-loading can be attributed to its larger CO2 adsorbed amount and longer charge lifetime as compared with TiO2-0 0 1, while the Pt nanoparticles loaded on TiO2-0 0 1 can more efficiently enhance the photoinduced carrier separation efficiency than that on TiO2-0 1 0, and therefore resulting in a photoactivity higher than the Pt-loaded TiO2-0 0 1. The above results provide an important indication about the effects of Pt-loading on the photocatalytic CO2 reduction activity of anatase TiO2 with different exposed facets, and shed light on the fabrication of novel nanostructured photocatalysts through morphological control for high conversion efficiency in the CO2 resource utilization.

BiOBr-g-C3N4 inorganic–organic composite photocatalysts were synthesized by a one-step chemical bath method at low temperature and characterized by X-ray diffraction patterns (XRD), Fourier transform infrared (FT-IR), thermo gravimetric (TG), X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HRTEM) and UV–vis diffuse reflectance spectra (DRS). The BiOBr-g-C3N4 composite showed much higher visible-light-driven (VLD) photocatalytic activity than pure g-C3N4 and BiOBr for rhodamine B (RhB) degradation. The photocatalytic mechanism analysis revealed that the interreaction between BiOBr and g-C3N4 is a kind of facet coupling between BiOBr-{0 0 1} and g-C3N4-{0 0 2}. The active species trapping and quantification experiments indicated that the photoinduced charges transfer between these facets resulted in the efficient charge separation.

Highly biocompatible superparamagnetic Fe 3 O 4 nanoparticles were synthesized by amide of folic acid (FA) ligands and the NH 2 -group onto the surface of Fe 3 O 4 nanoparticles. The as-synthesized folate-conjugated Fe 3 O 4 nanoparticles were characterized by X-ray diffraction diffractometer, transmission electron microscope, FT-IR spectrometer, vibrating sample magnetometer, and dynamic light scattering instrument. The in vivo labeling effect of folate-conjugated Fe 3 O 4 nanoparticles on the hepatoma cells was investigated in tumor-bearing rat. The results demonstrate that the as-prepared nanoparticles have cubic structure of Fe 3 O 4 with a particle size of about 8 nm and hydrated diameter of 25.7 nm at a saturation magnetization of 51 A·m 2 /kg. These nanoparticles possess good physiological stability, low cytotoxicity on human skin fibroblasts and negligible effect on Wistar rats at the concentration as high as 3 mg/kg body mass. The folate-conjugated Fe 3 O 4 nanoparticles could be effectively mediated into the human hepatoma Bel 7402 cells through the binding of folate and folic acid receptor, enhancing the signal contrast of tumor tissue and surrounding normal tissue in MRI imaging. It is in favor of the tumor cells labeling, tracing, magnetic resonance imaging (MRI) target detection and magnetic hyperthermia.

Anatase TiO2 crystals with {1 0 1}–{0 0 1} and {0 1 0}–{0 0 1} two facets coexistence were synthesized by (NH4)2TiF6 acting as titanium and fluorine sources and the photocatalytic activity of the samples were investigated. The replacement of {1 0 1} by {0 1 0} facets inhibits the photocatalytic activity of anatase TiO2. The mechanism was examined by photoluminescence spectrum, time-resolved photoluminescence spectra, field emission scanning electron microscope (FESEM) images of selected deposition of Ag, surface atoms structures and electronic band structures of anatase TiO2 facets. The results demonstrated that photoinduced charge transfer properties between {1 0 1} facets and {0 0 1} facets resulted in the efficient charge separation. Replacing {1 0 1} by {0 1 0}, the charge transfer mechanism was altered and the photoinduced electron–hole pairs cannot be separated well. The photocatalytic activity of it has thus been inhibited.

BiOI thin film (BiOI TF) was prepared via a low temperature chemical vapor transport (CVT) route for the first time, and characterized by X-ray diffraction, X-ray photoelectron spectroscopy, field emission scanning electron microscopy, transmission electron microscopy, high-resolution transmission electron microscopy, fast-Fourier transform pattern and UV–vis diffuse reflectance. As-synthesized BiOI thin film was composed of high symmetrical BiOI nanosheets with dominant exposed {0 0 1} facets. It displayed better photocatalytic activity, durability and selectivity than benchmark P25 TiO 2 thin film and the origin come from the layered structure and good photoelectrochemical performance, CVT immobilization, the 100% terminal oxygen atoms of {0 0 1} facets, respectively. At end, the photocatalytic mechanism with O 2 − production was studied.

The CNTs–WO3 hybrid nanostructures were fabricated by solvothermal synthesis. The morphologies, phase structures and optical properties of the nanostructures were investigated by TEM, XRD, UV–vis DRS and XPS respectively. The CNTs–WO3 hybrid nanostructures exist higher photocatalytic activity than pure WO3 nanosheets and the mechanical mixture of WO3 and CNTs for the degradation of methyl blue (MB) under visible light. This is attributed to their large surface area, absorption enhancement in visible light region and effective separation of electrons and holes. The presence of radical scavengers such as KI, Fe3 + and methanol in photocatalytic experiments demonstrates that photogenerated electrons are responsible for the photocatalytic degradation of MB on CNTs–WO3.

Summary Despite the clinical successes fostered by immune checkpoint inhibitors, mechanisms underlying PD-1 upregulation in tumor-infiltrating T cells remain an enigma. Here, we show that tumor-repopulating cells (TRCs) drive PD-1 upregulation in CD8 + T cells through a transcellular kynurenine (Kyn)-aryl hydrocarbon receptor (AhR) pathway. Interferon-γ produced by CD8 + T cells stimulates release of high levels of Kyn produced by TRCs, which is transferred into adjacent CD8 + T cells via the transporters SLC7A8 and PAT4. Kyn induces and activates AhR and thereby upregulates PD-1 expression. This Kyn-AhR pathway is confirmed in both tumor-bearing mice and cancer patients and its blockade enhances antitumor adoptive T cell therapy efficacy. Thus, we uncovered a mechanism of PD-1 upregulation with potential tumor immunotherapeutic applications.

The mixture of the anionic O,O′-bis(sodium 2-lauricate)- p -benzenediol (C 11 p PHCNa) and cationic (oligoona)alkanediyl-α, ω-bis(dimethyldodecylammonium bromide) (C 12 -2-E x -C 12 ·2Br) gemini surfactants has been investigated by surface tension and pyrene fluorescence. The results show that the surface tension γ drops faster with total surfactant concentration C T for α 1 = 0.1 or 0.3 than for α 1 = 0.7 or 0.9, where α 1 is the mole fraction of C 11 p PHCNa in the bulk solution on a surfactant-only basis. The fast drop in γ for α 1 γ for α 1 > 0.5 is attributed to the pre-aggregation in the solution before the critical micelle concentration cmc . A possible mechanism is proposed.

The purpose of the present study was to correlate the in vitro level of HIV Env expression by recombinant modified vaccinia virus Ankara (rMVA) with immunogenicity in mice. A 5-fold difference in Env synthesis was achieved at the translational level by the presence or absence of an out-of-frame initiation codon upstream of the env gene. This perturbation had no effect on the size or processing of Env. In contrast to the variation in Env synthesis, the rMVAs produced similar amounts of HIV Gag, which were expressed from identical cassettes. Mice immunized with the higher Env expressing rMVAs had about 15-fold higher titers of Env antibodies and several fold higher frequencies of Env-specific CD8+ and CD4+ T cells than mice immunized with the low expresser. The greater immune response achieved by high expression was maintained over a 100-fold dose range. Importantly, enhanced Env immune responses did not come at the expense of lower Gag T cell responses. These data suggest that for high immunogenicity, rMVAs should be engineered to produce the most recombinant protein that can be achieved without compromising the growth and stability of the rMVA.

The micellization of C11pPHCNa, a carboxylated gemini surfactant with an p-Oxybenzene residue in the spacer, in aqueous solution at pH 12 was characterized by the absorption and the fluorescence spectra of the p-Oxybenzene residue. The critical micelle concentration of C11pPHCNa was determined by the absorption spectra to be 0.0940 mmol L−1, which agreed well with that measured by surface tension technique. The fluorescent intensity of C11pPHCNa aqueous solution rapidly increased with increasing C11pPHCNa concentration (C) then reduced when C was beyond 0.45 mmol L−1, which meant the self-quenching occurring. At fixed C, the time-resolved and the steady-state fluorescence quenching with the p-Oxybenzene residue as the intrinsic probe and with methyl viologen (MV2+) as the extrinsic quencher could be used to measure the aggregation number (N) of C11pPHCNa micelle. The results showed the N for the micelle formed at C = 1.5 mmol L−1 was 14.5 and gradually increased with further increasing C. This indicated the more and more molecules packed within a micelle with increasing C, which explained well the fluorescence self-quenching when C was beyond 0.45 mmol L−1.

Here we conduct dose-response studies for in vitro expression and in vivo immunogenicity for a recombinant modified vaccinia Ankara (MVA) vaccine that expresses HIV Gag, Pol, and Env proteins. The dose-response studies for in vitro expression used fluorescent-activated cell sorting to score Gag- and Env-expressing cells and showed good increases for antigen expression with increasing MVA dose. In these studies, a 1000-fold increase in the dose of MVA resulted in a 300-fold increase in the frequency of antigen-expressing cells. In contrast, dose-response studies for in vivo immunogenicity showed

Zika virus (ZIKV) is associated with severe neuropathology in neonates as well as Guillain-Barre syndrome and other neurologic disorders in adults. Prolonged viral shedding has been reported in semen, suggesting the presence of anatomic viral reservoirs. Here we show that ZIKV can persist in cerebrospinal fluid (CSF) and lymph nodes (LN) of infected rhesus monkeys for weeks after virus has been cleared from peripheral blood, urine, and mucosal secretions. ZIKV-specific neutralizing antibodies correlated with rapid clearance of virus in peripheral blood but remained undetectable in CSF for the duration of the study. Viral persistence in both CSF and LN correlated with upregulation of mechanistic target of rapamycin (mTOR), proinflammatory, and anti-apoptotic signaling pathways, as well as downregulation of extracellular matrix and cell signaling pathways. These data raise the possibility that persistent or occult neurologic and lymphoid disease may occur following clearance of peripheral virus in ZIKV-infected individuals.