The Microbial Tryptophan Metabolite Contributes to the Remission of Salmonella typhimurium Infection in Mice.

Salmonella enterica serovar Typhimurium (S. Tm) causes severe foodborne diseases. Interestingly, gut microbial tryptophan (Trp) metabolism plays a pivotal role in such infections by a yet unknown mechanism. This study aimed to explore the impact of Trp metabolism on S. Tm infection and the possible mechanisms involved. S. Tm-infected C57BL6/J mice were used to demonstrate the therapeutic benefits of the Bacillus velezensis JT3-1 (B. velezensis/JT3-1) strain or its cell-free supernatant in enhancing Trp metabolism. Targeted Trp metabolomic analyses indicated the predominance of indole-3-lactic acid (ILA), an indole derivative and ligand for aryl hydrocarbon receptor (AHR). Based on the 16S amplicon sequencing and correlation analysis of metabolites, we found that B. velezensis supported the relative abundance of Lactobacillus and Ligilactobacillus in mouse gut and showed positive correlations with ILA levels. Moreover, AHR and its downstream genes (especially IL-22) significantly increased in mouse colons after B. velezensis or cell-free supernatant treatment, suggesting the importance of AHR pathway activation. In addition, ILA was found to stimulate primary mouse macrophages to secrete IL-22, which was antagonized by CH-223191. Furthermore, ILA could protect mice from S. Tm infection by increasing IL-22 in Ahr+/- mice, but not in Ahr-/- mice. Finally, Trp-rich feeding showed amelioration of S. Tm infection in mice, and the effect depended on gut microbiota. Taken together, these results suggest that B. velezensis-associated ILA contributes to protecting mice against S. Tm infection by activating the AHR/IL-22 pathway. This study provides insights into the involvement of microbiota-derived Trp catabolites in protecting against Salmonella infection.

Phenolylazoindole scaffold for facilely synthesized and bis-functional photoswitches combining controllable fluorescence and antifungal properties using theoretical methods.

Functionalization is a major challenge for the application of photoswitches. With the aim to develop novel bis-functional azo photoswitches with stationary photophysical properties, a series of phenolylazoindole derivatives were designed, synthesized, and characterized via NMR spectroscopy studies and high-resolution mass spectrometry (HRMS). Herein, UV/Vis and 1H NMR spectra revealed that the photostationary state (PSS) proportions for PSScis and PSStrans were 76-80% and 68-81%, respectively. Furthermore, the thermal half-lives (t1/2) of compounds A2-A4 and B2 ranged from 0.9 to 5.3 h, affected by the diverse substituents at the R1 and R2 positions. The results indicated that azo photoswitches based on the phenolylazoindole scaffold had stationary photophysical properties and wouldn't be excessively affected by modifying the functional groups. Compounds A4 and B2, which were modified with an aryl group, also exhibited fluorescence emission properties (the quantum yields of A4 and B2 were 2.32% and 13.34%) through the modification of the flexible conjugated structure (benzene) at the R2 position. Significantly, compound C1 was obtained via modification with a pharmacophore in order to acquire antifungal activities against three plant fungi, Rhizoctonia solani (R. solani), Botrytis cinerea (B. cinerea), and Fusarium graminearum (F. graminearum). Strikingly, the inhibitory activity of the cis-isomer of compound C1towards R. solani (53.3%) was significantly better than that of the trans-isomer (34.2%) at 50 µg mL-1. In order to further reveal the antifungal mechanism, molecular docking simulations demonstrated that compound C1 effectively integrates into the cavity of succinate dehydrogenase (SDH); the optically controlled cis-isomer showed a lower binding energy with SDH than that of the trans-isomer. This research confirmed that phenolylazoindole photoswitches can be appropriately applied as molecular regulatory devices and functional photoswitch molecules via bis-functionalization.

Comprehensive Analysis of Fibroblast Activation Protein Expression in Interstitial Lung Diseases.

Rationale: Sustained activation of lung fibroblasts and the resulting oversynthesis of the extracellular matrix are detrimental events for patients with interstitial lung diseases (ILDs). Lung biopsy is a primary evaluation technique for the fibrotic status of ILDs, and is also a major risk factor for triggering acute deterioration. Fibroblast activation protein (FAP) is a long-known surface biomarker of activated fibroblasts, but its expression pattern and diagnostic implications in ILDs are poorly defined. Objectives: The present study aims to comprehensively investigate whether the expression intensity of FAP could be used as a potential readout to estimate or measure the amounts of activated fibroblasts in ILD lungs quantitatively. Methods: FAP expression in human primary lung fibroblasts as well as in clinical lung specimens was first tested using multiple experimental methods, including real-time quantitative PCR (qPCR), Western blot, immunofluorescence staining, deep learning measurement of whole slide immunohistochemistry, as well as single-cell sequencing. In addition, FAP-targeted positron emission tomography/computed tomography imaging PET/CT was applied to various types of patients with ILD, and the correlation between the uptake of FAP tracer and pulmonary function parameters was analyzed. Measurements and Main Results: Here, it was revealed, for the first time, FAP expression was upregulated significantly in the early phase of lung fibroblast activation event in response to a low dose of profibrotic cytokine. Single-cell sequencing data further indicate that nearly all FAP-positive cells in ILD lungs were collagen-producing fibroblasts. Immunohistochemical analysis validated that FAP expression level was closely correlated with the abundance of fibroblastic foci on human lung biopsy sections from patients with ILDs. We found that the total standard uptake value (SUV) of FAP inhibitor (FAPI) PET (SUVtotal) was significantly related to lung function decline in patients with ILD. Conclusions: Our results strongly support that in vitro and in vivo detection of FAP can assess the profibrotic activity of ILDs, which may aid in early diagnosis and the selection of an appropriate therapeutic window.

Conversion of Phosphogypsum into Porous Calcium Silicate Hydrate for the Removal and Recycling of Pb(II) and Cd(II) from Wastewater.

The discharge of lead and cadmium wastewater, along with the pollution caused by phosphogypsum, represents a particularly urgent environmental issue. This study employed a straightforward hydrothermal method to convert phosphogypsum into porous calcium silicate hydrate (P-CSH), which was then used to remove and recover Pb(II) and Cd(II) from wastewater. The adsorption capacities of P-CSH for Pb(II) and Cd(II) were notably high at 989.3 mg/g and 290.3 mg/g, respectively. The adsorption processes adhered to the pseudo-second-order kinetics model and the Langmuir isotherm model. Due to identical adsorption sites on P-CSH for both Pb(II) and Cd(II), competitive interaction occurred when both ions were present simultaneously. Additionally, the adsorption efficacy was minimally impacted by the presence of common coexisting cations in wastewater. The dominant mechanisms for removing Pb(II) and Cd(II) via P-CSH were chemical precipitation and surface complexation. Moreover, the adsorbed heavy metals were efficiently separated and reclaimed from the wastewater through a stepwise desorption process. The primary components of the residue from stepwise desorption were quartz and amorphous SiO2. Following dissolution via pressurized alkaline leaching, this residue could be recycled for synthesizing P-CSH. This research offered a new strategy for the resourceful use of phosphogypsum and heavy metal wastewater.

Tracking tumor alteration in glioma through serum fibroblast activation protein combined with image.

PURPOSE: Detecting tumor progression of glioma continues to pose a formidable challenge. The role of fibroblast activation protein (FAP) in gliomas has been demonstrated to facilitate tumor progression. Glioma-circulating biomarkers have not yet been used in clinical practice. This study seeks to evaluate the feasibility of glioma detection through the utilization of a serum FAP marker. METHODS: We adopted enzyme-linked immunosorbent assay (ELISA) technique to quantify the relative FAP level of serum autoantibodies in a cohort of 87 gliomas. The correlation between preoperative serum autoantibody relative FAP levels and postoperative pathology, including molecular pathology was investigated. A series of FAP tests were conducted on 33 cases of malignant gliomas in order to ascertain their efficacy in monitoring the progression of the disease in relation to imaging observations. To validate the presence of FAP expression in tumors, immunohistochemistry was conducted on four gliomas employing a FAP-specific antibody. Additionally, the investigation encompassed the correlation between postoperative tumor burden, as assessed through volumetric analysis, and the relative FAP level of serum autoantibodies. RESULTS: A considerable proportion of gliomas exhibited a significantly increased level of serum autoantibody relative FAP level. This elevation was closely associated with both histopathology and molecular pathology, and demonstrated longitudinal fluctuations and variations corresponding to the progression of the disease The correlation between the rise in serum autoantibody relative FAP level and tumor progression and/or exacerbation of symptoms was observed. CONCLUSIONS: The measurement of serum autoantibody relative FAP level can be used to detect the disease as a valuable biomarker. The combined utilization of its detection alongside MR imaging has the potential to facilitate a more accurate and prompt diagnosis.

LncRNA MALAT1 Promoted Neuronal Necroptosis in Cerebral Ischemia-reperfusion Mice by Stabilizing HSP90.

The objective of this research was to investigate the role of lncRNA MALAT1 and HSP90 in the regulation of neuronal necroptosis in mice with cerebral ischemia-reperfusion (CIR). We used male C57BL/6J mice to establish a middle cerebral artery occlusion (MCAO) model and conducted in vitro experiments using the HT-22 mouse hippocampal neuron cell line. The cellular localization of NeuN and MLKL, as well as the expression levels of neuronal necroptosis factors, MALAT1, and HSP90 were analyzed. Cell viability and necroptosis were assessed, and we also investigated the relationship between MALAT1 and HSP90. The results showed that MALAT1 expression increased after MCAO and oxygen-glucose deprivation/re-oxygenation (OGD/R) treatment in both cerebral tissues and cells compared with the control group. The levels of neuronal necroptosis factors and the co-localization of NeuN and MLKL were also increased in MCAO mice compared with the Sham group. MALAT1 was found to interact with HSP90, and inhibition of HSP90 expression led to decreased phosphorylation levels of neuronal necroptosis factors. Inhibition of MALAT1 expression resulted in decreased co-localization levels of NeuN and MLKL, decreased phosphorylation levels of neuronal necroptosis factors, and reduced necroptosis rate in cerebral tissues. Furthermore, inhibiting MALAT1 expression also led to a shorter half-life of HSP90, increased ubiquitination level, and decreased phosphorylation levels of neuronal necroptosis factors in cells. In conclusion, this study demonstrated that lncRNA MALAT1 promotes neuronal necroptosis in CIR mice by stabilizing HSP90.

Skeletal Editing of Dibenzolactones to Fluorenes via Ni- or Pd-Catalyzed Decarboxylation.

The skeletal editing of dibenzolactones to fluorenes by Ni- or Pd-catalyzed decarboxylation is reported. In contrast to previously reported intramolecular decarboxylative couplings, inductively electron-withdrawing ortho substituents on the aryl carboxylate moiety and metal additives are not required. The decarboxylation reaction proceeds cleanly and can be applied to the skeletal editing of a natural product analogue. Mechanistic observations are consistent with stabilization of the carboxylate-ligated Ni complex over the Ni-carboxylate ion pair, which is the key factor in promoting the challenging decarboxylation step in the catalytic cycle.

Characteristics of thermal pollution from stormwater runoff from impermeable/permeable pavement surfaces via a lab-scale experiment.

Thermal pollution from stormwater runoff has been the focus of many studies in recent years due to its potential harm to aquatic microorganisms. However, there were few studies on the thermal pollution caused by stormwater runoff from various types of urban pavement surfaces. A lab-scale experiment was conducted to compare the thermal load of stormwater runoff from impermeable and permeable pavements and the influencing factors were investigated. The experimental findings demonstrated that the rainfall return period and initial temperature of various pavement surfaces significantly impacted the thermal load. The stormwater runoff absorbed more heat as the initial temperature, and rainfall return period increased. The difference of the thermal load of stormwater runoff between permeable brick pavement (PBP) and the impermeable asphalt pavement (IAP) increased from 305.26 to 436.70 kJ/m2, when the initial surface temperature rose from 35 to 47 °C. The average runoff temperature decreased by 1.39-1.90 °C for PBP compared to the IAP, with an increase in surface temperature from 35 to 47 °C. Under the various initial surface temperatures, the mean temperature of the infiltration effluent from the PBP was 3.12-4.20 °C lower than the average temperature of stormwater runoff from the surface layer. Therefore, a PBP can effectively alleviate thermal pollution from stormwater runoff and safeguard the receiving waters' quality.

Effect of different MIT rainfall event division methods on volume capture ratio of annual rainfall based on bioretention assessment.

Volume capture ratio of annual rainfall (VCRAR) is the key parameter of low-impact development (LID) facilities design, which is significantly affected by the rainfall event division method. However, there is no universal agreement on how to determine an optimal division method to achieve it. A modified minimum inter-event time (MIT) method based on MATLAB software was proposed to find an optimal MIT value. The result showed that the optimal MIT value in Beijing is 200 min based on the daily rainfall data from 1987 to 2016, and the annual average rainfall events were 34.2 with an average rainfall depth of 13.7 mm. Taking bioretention facilities as an example, the errors of design VCRAR under different MIT values were compared based on a Stormwater Management Model (SWMM). The results showed that when design VCRAR was ≤50, 55-60, 60-75, 75-80 and >80%, the optimal MIT value for LID facilities design was 60, 120, 200, 360 and 1,440 min, respectively. Therefore, the optimal MIT should be flexibly selected with the changing of design VCRAR, to ensure that LID facilities meet the design goals.

"Electron Complementation"-Induced Molybdenum Nitride/Co-Anchored Graphitic Carbon Nitride Porous Nanoparticles for Efficient Overall Water Splitting.

Maximizing the usable space of electrocatalysts and fine-tuning the interface geometry as well as the electronic structure to facilitate hydrogen and oxygen evolution reactions (HER and OER) have always been the focus of research. Herein, a homogeneous porous nanoparticle construction strategy was proposed, in which molybdenum nitride (Mo2N) particles were prepared by controlled heat treatment of the precursor nanoparticle induced by polyethylene glycol, and the Mo2N/Co-C3N4 heterostructure with a pore size of about 1.13 nm was obtained by compounding Co-anchored graphitic carbon nitride. In particular, exploring the change of charge distribution at the interface based on the principle of "electron complementation" shows that under the regulation of nitrogen with high electronegativity, the affinity of active site Co to oxygenated species in the OER process and the adsorption as well as cleavage ability of HER reactants in the active site were effectively optimized. Thus, Mo2N/Co-C3N4 not only inherits the functions of each component, but also provides an ideal heterogeneous interface for exhibiting impressive bifunctional activity, which only needs 100 and 210 mV to deliver 10 mA cm-2 for the HER and OER, respectively. In addition, the Mo2N/Co-C3N4 catalyst also demonstrates high overall water splitting stability with a slight current decrease after 95 h. Manipulating the electronic structure of multiple sites by constructing electronically complementary interfaces may provide another avenue to develop highly active catalysts for overall water splitting and other applications.

Screening of ulcerative colitis biomarkers and potential pathways based on weighted gene co-expression network, machine learning and ceRNA hypothesis.

BACKGROUND: Ulcerative colitis (UC) refers to an intractable intestinal inflammatory disease. Its increasing incidence rate imposes a huge burden on patients and society. The UC etiology has not been determined, so screening potential biomarkers is critical to preventing disease progression and selecting optimal therapeutic strategies more effectively. METHODS: The microarray datasets of intestinal mucosal biopsy of UC patients were selected from the GEO database, and integrated with R language to screen differentially expressed genes and draw proteins interaction network diagrams. GO, KEGG, DO and GSEA enrichment analyses were performed to explore their biological functions. Through machine learning and WGCNA analysis, targets that can be used as UC potential biomarkers are screened out. ROC curves were drawn to verify the reliability of the results and predicted the mechanism of marker genes from the aspects of immune cell infiltration, co-expression analysis, and competitive endogenous network (ceRNA). RESULTS: Two datasets GSE75214 and GSE87466 were integrated for screening, and a total of 107 differentially expressed genes were obtained. They were mainly related to biological functions such as humoral immune response and inflammatory response. Further screened out five marker genes, and found that they were associated with M0 macrophages, quiescent mast cells, M2 macrophages, and activated NK cells in terms of immune cell infiltration. The co-expression network found significant co-expression relationships between 54 miRNAs and 5 marker genes. According to the ceRNA hypothesis, NEAT1-miR-342-3p/miR-650-SLC6A14, NEAT1-miR-650-IRAK3, and XIST-miR-342-3p-IRAK3 axes were found as potential regulatory pathways in UC. CONCLUSION: This study screened out five biomarkers that can be used for the diagnosis and treatment of UC, namely SLC6A14, TIMP1, IRAK3, HMGCS2, and APOBEC3B. Confirmed that they play a role in the occurrence and development of UC at the level of immune infiltration, and proposed a potential RNA regulatory pathway that controls the progression of UC.

Coal gangue modified bioretention system for runoff pollutants removal and the biological characteristics.

In this study, coal gangue (CG) was applied as media in bioretention system to remove runoff pollutant. CG modified bioretention systems show good removal efficiency towards runoff pollutant due to the high adsorption capacity of CG. The removal of total phosphorus (TP), total nitrogen (TN), ammonia (NH4+-N) and chemical oxygen demand (COD) by CG modified bioretention systems was influenced by diverse rainfall conditions including rainfall concentration, recurrence period and drying period, and their removal rate ranged 94-99%, 30-70%, 83-97% and 33-86%, respectively. The effluent concentration of Zn, Pb and Cu was as low as 3.14-10.99 µg/L, 0.66-2.56 µg/L and 0.60-3.15 µg/L, respectively. In addition, CG could promote the plant heavy metal uptake and thus decrease their accumulation in soil to a certain extent. Meanwhile, Malondialdehyde (MDA) content and peroxidases (POD) activities of plants in CG modified bioretention were lower than that in tradition bioretention, indicating that CG could help plants recovery and lessened the oxidative stress for the negative impact of high heavy metals accumulation. CG-based media alleviated the inhibitory effect of rainwater runoff pollutant accumulation (especially heavy metals) on microbial diversity and the enhancement of the dominant bacteria (such as Proteobacteria and Bacteroidota) could conduce the nutrients removal in the bioretention systems. In overall, this study demonstrated that the CG modified bioretention systems show an excellent removal performance combine with biological effects.

Effect mechanism of litter extract from Alternanthera philoxeroides on the selective absorption of heavy metal ions by amphoteric purple soil.

Plant litter causes a serious waste of resources. Thus, plant litter extract (LE) should be used in the soil remediation of heavy metals. In this study, different proportions of LE from the Alternanthera philoxeroides were used to modify dodecyl dimethyl betaine (BS)-modified purple soil (P). The basic physicochemical properties of LE + BS-modified Ps (LE + BS-Ps) were determined, and the microscopic morphology of LE + BS-Ps was studied by using scanning electron microscopy (SEM), energy dispersion spectroscopy (EDS), Fourier transform infrared (FTIR) spectroscopy, and specific surface area detection. The isothermal adsorption characteristics of heavy metal ions (Pb2+, Cu2+, and Cr6+) on different LE + BS-Ps were investigated by the batch method, and the effect mechanisms of temperature, pH, ionic strength, and LE + BS-P's property were compared. Results showed that the cation exchange capacity and specific surface area of LE + BS-Ps increased, pH of LE + BS-Ps decreased, and TOC of LE + BS-Ps increased first and then decreased with increasing proportion of LE. FTIR, SEM, and EDS results proved that LE was modified on the surface of BS-P. Langmuir and Freundlich models could be used to describe the adsorption isotherms of heavy metal ions on different LE + BS-Ps, and the fitting correlation of the Langmuir model was higher than that of the Freundlich model. The maximum adsorption capacity (qm) of Pb2+, Cu2+, and Cr6+ were 107.60-295.66, 133.00-342.11, and 33.59-75.41 mmol/kg, respectively. The qm of Pb2+, Cu2+, and Cr6+ on LE + BS-Ps all increased first and then decreased with increasing proportion of LE, and the peak value was observed in 20%LE + BS-Ps. High pH improved Pb2+ and Cu2+ adsorption but inhibited Cr6+ adsorption. The adsorption amounts of Pb2+, Cu2+, and Cr6+ all increased first and then decreased with incresing ionic strength and were maintained at the maximum value of 0.1-0.2 mol/L. The Pb2+, Cu2+, and Cr6+ adsorption mechanisms on different LE + BS-Ps showed a positive temperature effect and presented spontaneous, exothermic and entropy-adding processes.

Opportunities and challenges in targeted therapy and immunotherapy for pancreatic cancer.

Pancreatic cancer is one of the most malignant tumours with a poor prognosis. In recent years, the incidence of pancreatic cancer is on the rise. Traditional chemotherapy and radiotherapy for pancreatic cancer have been improved, first-line and second-line palliative treatments have been developed, and adjuvant treatments have also been used in clinical. However, the 5-year survival rate is still less than 10% and new treatment methods such as targeted therapy and immunotherapy need to be investigated. In the past decades, many clinical trials of targeted therapies and immunotherapies for pancreatic cancer were launched and some of them showed an ideal prospect in a subgroup of pancreatic cancer patients. The experience of both success and failure of these clinical trials will be helpful to improve these therapies in the future. Therefore, the current research progress and challenges of selected targeted therapies and immunotherapies for pancreatic cancer are reviewed.

Transferable Active Centers of Strongly Coupled MoS2@Sulfur and Molybdenum Co-doped g-C3N4 Heterostructure Electrocatalysts for Boosting Hydrogen Evolution Reaction in Both Acidic and Alkaline Media.

Designing an excellent acidic and alkaline general-purpose hydrogen evolution electrocatalyst plays an important role in promoting the development of the energy field. Here, a feasible strategy is reported to use the strongly coupled MoS2@sulfur and molybdenum co-doped g-C3N4 (MoS2@Mo-S-C3N4) heterostructure with transferable active centers for catalytic reactions in acidic and alkaline media. Research studies have shown that the unsaturated S site at the edge of MoS2 and the active N atom on the Mo-S-C3N4 substrate are, respectively, the active centers of acidic and alkaline hydrogen evolution reaction. Specifically, Mo-S-C3N4 is regarded as a synergistic catalyst for the active species MoS2 in acidic hydrogen evolution, while MoS2 acts as a co-catalyst when the alkaline active species are transferred to Mo-S-C3N4. The coordination of the electrons between the interfaces achieves a synergistic balance, which provides the optimal sites for the adsorption of the reactants. Such an electrocatalyst exhibits overpotentials of 193 and 290 mV at 10 mA cm-2 in 0.5 M H2SO4 and 1 M KOH, respectively, which was better than numerous previous reports. This research provides an outstanding avenue to realize multifunctional electrocatalysts.

Optimal rare-earth (La, Y and Sm) doping conditions and enhanced mechanism for photocatalytic application of ceria nanorods.

Morphological tuning or additional cation doping is one of the potential and simple methods to enhance the photocatalytic properties of ceria, in which rare-earth element doped ceria nanorods (CeO2-RE NRs) are expected to be a promising photocatalyst with high activity. But the optimal doping conditions, including the variety and concentration of RE elements are ambiguous, and the contribution of doped RE ions to the enhancement of photocatalytic activity needs to be further studied. In this work, we doped La, Y and Sm with a wide range of 0%-30% into CeO2 NRs, and investigated the phase, morphology, band gap, oxygen vacancy concentration, PL spectra and photocatalytic activity variation under different doping conditions. All synthesized CeO2-RE NRs possessed a good nanorod morphology except the 15 and 30% Y-doped samples. The energy band gaps of the synthesized samples changed slightly; the 10% CeO2-RE NRs with the narrowest band gaps possessed the higher photocatalytic performance. The most outstanding photocatalyst was found to be the 10% Y-doped CeO2 NRs with a methylene blue photodegradation ratio of 85.59% and rate constant of 0.0134 min-1, which is particularly associated with a significant higher oxygen vacancy concentration and obviously lower recombination rate of photogenerated e-/h+ pairs. The doped RE ions and the promotion of oxygen vacancy generation impede the recombination of photogenerated carriers, which is proposed as the main reason to enhance the photocatalytic property of CeO2.

Tumor-associated antigen-based personalized dendritic cell vaccine in solid tumor patients.

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).

Disparate Catalytic Scaffolds for Atroposelective Cyclodehydration.

Catalysts that control stereochemistry are prized tools in chemical synthesis. When an effective catalyst is found, it is often explored for other types of reactions, frequently under the auspices of different mechanisms. As successes mount, a unique catalyst scaffold may become viewed as "privileged". However, the mechanistic hallmarks of privileged catalysts are not easily enumerated or readily generalized to genuinely different classes of reactions or substrates. We explored the concept of scaffold uniqueness with two catalyst types for an unusual atropisomer-selective cyclodehydration: (a) C2-symmetric chiral phosphoric acids and (b) phosphothreonine-embedded, peptidic phosphoric acids. Pragmatically, both catalyst scaffolds proved fertile for enantioselective/atroposelective cyclodehydrations. Mechanistic studies revealed that the determinants of often equivalent and high atroposelectivity are different for the two catalyst classes. A data-descriptive classification of these asymmetric catalysts reveals an increasingly broad set of catalyst chemotypes, operating with different mechanistic features, that creates new opportunities for broad and complementary application of catalyst scaffolds in diverse substrate space.

Enhanced Electrocatalytic Performance through Body Enrichment of Co-Based Bimetallic Nanoparticles In Situ Embedded Porous N-Doped Carbon Spheres.

Extending available body space loading active species and controllably tailoring the d-band center to Fermi level of catalysts are of paramount importance but extremely challenging for the enhancement of electrocatalytic performance. Herein, a melamine-bridged self-construction strategy is proposed to in situ embed Co-based bimetallic nanoparticles in the body of N-doped porous carbon spheres (CoM-e-PNC), and achieve the controllable tailoring of the d-band center position by alloying of Co and another transition metal M (M = Ni, Fe, Mn, and Cu). The enrichment and exposure of the active sites in the body interior of porous carbon spheres, and the best balance between the adsorption of OH species and the desorption of O2 induced by optimizing the d-band center position, collectively enhance the oxygen evolution reaction (OER) performance. Meanwhile, the relationship of d-band center position and OER activity is found to exhibit the volcano curve rule, where the CoNi-e-PNC catalyst shows optimal OER performance with an overpotential of 0.24 V at 10 mA cm-2 in alkaline media, outperforming those of the ever-reported CoNi-based catalysts. Besides, CoNi-e-PNC catalyst also demonstrates high OER stability with slight current decrease after 100 h.

Prior-information-free single-shot scattering imaging beyond the memory effect.

Imaging beyond the memory effect (ME) is critical to seeing through the scattering media. Methods proposed before have suffered from invasive point spread function measurement or the availability of prior information of the imaging targets. In this Letter, we propose a prior-information-free single-shot scattering imaging method to exceed the ME range. The autocorrelation of each imaging target is separated blindly from the autocorrelation of the recorded dual-target speckle via Fourier spectrum guessing and iterative energy constrained compensation. Working together with phase retrieval, dual targets exceeding the ME range can be reconstructed via a single shot. The effectiveness of the algorithm is verified by simulated experiments and a real imaging system.