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The clinical benefit of PD-1 blockade can be improved by combination with CTLA4 inhibition but is commensurate with significant immune-related adverse events suboptimally limiting the doses of anti-CTLA4 mAb that can be used. MEDI5752 is a monovalent bispecific antibody designed to suppress the PD-1 pathway and provide modulated CTLA4 inhibition favoring enhanced blockade on PD-1

Background: It is widely believed that Maillard reactions could affect the sensitization of allergens. However, the mechanism of action of methylglyoxal (MGO) production in Maillard reactions in the sensitization variation of glutenin (a predominant allergen in wheat) during heat processing is still unclear. Methods: This research evaluated the effect of MGO on the immune response against glutenin in a mouse model. The resulting variations in conformation and corresponding digestibility of glutenin were determined. The immune response and gut microflora variation in mice were analyzed following administering of glutenin and MGO-glutenin. Results: The results of the study showed that MGO-glutenin induced a lower immune response than native glutenin. Cytokine analysis showed that MGO-glutenin regulated mouse immune response by inducing Treg differentiation. MGO decoration changed the structure and digestibility of glutenin. In addition, MGO-glutenin contributes to the maintenance of the beneficial gut microflora. Conclusion: MGO decoration of glutenin during heat processing could alleviate the resulting allergic reaction in mice. Decoration with MGO appears to contribute to the aggregation of glutenin, potentially masking surface epitopes and abating sensitization. Furthermore, Bacteroides induced regulatory T-cell (Treg) differentiation, which may contribute to inhibition of the Th2 immune response and stimulation of immune tolerance.

Aging is regarded as a dominant risk factor for cancer. Additionally, inflammation and asthenic immune surveillance with aging may facilitate tumor formation and development. However, few studies have comprehensively analyzed the relationship between aging-related genes (AGs) and the prognosis, inflammation and tumor immunity of head and neck squamous cell carcinoma (HNSCC). Here, we initially screened 41 differentially expressed AGs from The Cancer Genome Atlas (TCGA) database. In the training set, a prognosis risk model with seven AGs (APP, CDKN2A, EGFR, HSPD1, IL2RG, PLAU and VEGFA) was constructed and validated in the TCGA test set and the GEO set (P < 0.05). Using univariate and multivariate Cox regression analyses, we confirmed that risk score was an independent prognostic factor of HNSCC patients. In addition, a high risk score was significantly correlated with immunosuppression, and high expression of PLAU, APP and EGFR was the main factor. Furthermore, we confirmed that a high risk score was significantly associated with levels of proinflammatory factors (IL-1α, IL-1β, IL-6 and IL-8) in HNSCC samples. Thus, this risk model may serve as a prognostic signature and provide clues for individualized immunotherapy for HNSCC patients.

On the basis of maintaining the original characteristics of each component, the composite material obtains the properties that the single component does not have through the synergy between the components. It is of great significance to understand the synergy between the components for the development of the composite. First of all, we prepared different emitting CdTe quantum dots (QDs), and then fabricated CdTe QDs@reduced graphene oxide (rGO) composites by a simple ultrasonic method. It is found that the fluorescence of QDs quenched, the photocurrent significantly improved, but the growth rate different from each other because of the different QDs. Afterwards, on the basis of naked QDs, hybrid SiO₂-coated QDs were fabricated by a two-step method. After that, hybrid SiO₂-coated CdTe QDs@rGO composites were prepared by the same method. It is found that the existence of the hybrid SiO₂ shell leads to the decrease of photocurrent of the composites before and after coating, but the specific capacitance significantly improved, and the cycle stability also better than the naked QDs. This research will make grapheme-based composites have broad application prospects in energy storage equipment.

Compared with conventional semiconductor quantum dots, hybrid SiO₂ coated CdTe QDs exhibited high stability, long fluorescent lifetime, high photoluminescence quantum yields, and well biocompatibility. In this paper, CdTe QDs with tunable PL from green to red emitting were prepared by an aqueous synthesis. A sol-gel process resulted in CdTe QDs coated with a hybrid SiO₂ shell contained CdS-like clusters to obtain red-shifted PL spectra, increased PL efficiency and high stability. The clusters were formed by the reaction of Cd

Homologous to E6AP C-terminus (HECT) E3 ubiquitin ligases play a critical role in various cellular pathways, including but not limited to protein trafficking, subcellular localization, innate immune response, viral infections, DNA damage responses and apoptosis. To date, 28 HECT E3 ubiquitin ligases have been identified in humans, and recent studies have begun to reveal how these enzymes control various cellular pathways by catalyzing the post-translational attachment of ubiquitin to their respective substrates. New studies have identified substrates and/or interactors with different members of the HECT E3 ubiquitin ligase family, particularly for E6AP and members of the neuronal precursor cell-expressed developmentally downregulated 4 (NEDD4) family. However, there still remains many unanswered questions about the specific roles that each of the HECT E3 ubiquitin ligases have in maintaining cellular homeostasis. The present Review discusses our current understanding on the biological roles of the HECT E3 ubiquitin ligases in the cell and how they contribute to disease development. Expanded investigations on the molecular basis for how and why the HECT E3 ubiquitin ligases recognize and regulate their intracellular substrates will help to clarify the biochemical mechanisms employed by these important enzymes in ubiquitin biology.

We have designed 2-domain anticancer peptides with RGD-based KLAK bi-functional short motifs (linear and cyclic analogues). RGD tripeptide acts as tumor blood vessel ‘homing’ motif while KLAK tetrapeptide internalized in mitochondria and causes cell apoptosis. All three peptides (RGDKLAK; HM, cyclic-RGDKLAK; HMC-1, and RGD-cyclic-KLAK; HMC-2) were conjugated with fluorescein isothiocyanate isomer-I (5-FITC; F) for in-vivo and in-vitro optical imaging studies. These fluorescent-peptide (FL-peptide) analogues were analyzed to possess αvβ3-integrin targeting affinity, high uptake in in-vitro cell binding assays followed by in-vivo tumor xenograft mice studies. Pharmacological profile reveals that F-HMC-1 analogue exhibited selectively and specifically higher affinity for αvβ3-integrin than other analogues in U87MG cells in comparison with HeLa cells. The subcutaneous U87MG tumor xenograft mice models clearly visualized the uptake of F-HMC-1 in tumor tissue in contrast with normal tissues with tumor-to-normal tissue ratio (T/NT = 15.9 ± 1.1) at 2 h post-injection. These results suggested that F-HMC-1 peptide has potential diagnostic applications for targeting αvβ3-integrin assessed by optical imaging study in U87MG tumor xenograft mice models.

Lysophosphatidic acid is a small extracellular signaling molecule, which is elevated in pathological conditions such as ischemic stroke and traumatic brain injury (TBI). LPA regulates the survival of neurons in various diseases. However, the molecular mechanisms underlying LPA-induced neuronal death remain unclear. Here we report that LPA activates LPA1 and LPA2 receptors, and the downstream MAPK pathway to induce the apoptosis of PC12 cells through mitochondrial dysfunction. LPA elicits the activation of ERK1/2, p38, and JNK pathways, decreases the expression of Bcl2, promotes the translocation of Bax, and enhances the activation of caspase-3, resulting in mitochondrial dysfunction and cell apoptosis. This process can be blocked by LPA1 receptor antagonist and LPA2 receptor antagonist and MAPK pathway inhibitors. Our results indicate that LPA1 receptor, LPA2 receptor and MAPK pathway play a critical role in LPA-induced neuronal injury. LPA receptors and MAPK pathways may be novel therapeutic targets for ischemic stroke and TBI, where excessive LPA signaling exist.

This study investigated performance and stability of increasing total solids (TS) content (10-30%) and feedstock-to-inoculum (F/I) ratios (1, 2) on anaerobic co-digestion of agricultural wastes. The cumulative methane yields generally decreased with the increasing TS content except for the TS content of 30% at F/I ratio of 1 and TS content of 10% at F/I ratio of 2. This was consistent with the maximum methane production rate (Rmax) and rate of the hydrolysis (Kh) stage in reactors. The pH, VFAs and NH4+-N content were positively correlated with increasing TS contents and F/I ratios. Economic analysis results indicated the net present value generally increased with increasing TS contents and TS content of 30% at F/I ratio of 1 had the highest net present value (5.7 million US$) and internal rate of return (41.9%). This indicated solid-state anaerobic digestion was financially attractive under analyzed conditions.

This is great significant to establish a method that extends the small molecules fluorescence emission wavelength to the near-infrared region (NIR) for in vivo imaging. Hence, we firstly reported a novel fluorogenic scaffold QOH that could extend its fluorescence wavelength from (λem = 555 nm) to NIR (λem = 720 nm) with a large Stokes shift (120 nm) by forming its N-quaternization product (QMOH). In addition, the effect of the introduction of substituent at different modification sites and the properties of substituent on the optical properties of QOH were fully discussed by theoretical calculation. To investigate the possibility of QOH as probe construction, the compound Q-SH and QM-R were synthesized and applied to detect H2S and H2O2 in vitro and in vivo, respectively. This study provided an efficient strategy to extend fluorescence emission to NIR and design fluorescence probes with large ratio variation for accurately imaging biomarkers in biological system.

Lithium metal has emerged as the most prospective candidate for the realization of improved battery systems. However, notorious Li dendrite formation and the huge volume effect during cycling critically impair the further practical deployment of Li metal batteries. Herein, we propose hierarchical Ni- and Co-based oxynitride (NiCoO2/CoO/Ni3N) nanoarrays with superior lithiophilicity on a three-dimensional nickel foam (NiCoON/NF) as a host for highly stable Li metal anodes. The uniform nitrogen-infused nanorod-on-nanosheet arrays present improved electrical conductivity and an increased concentration of active sites with oxygen vacancies to enhance the surface lithiophilicity, which effectively facilitates homogeneous Li nucleation/growth. Moreover, the hyperbranched structure can induce a homogeneous distribution of Li-ion flux, owing to the enlarged surface area, thereby providing sufficient space to store deposited lithium and relieve the volume expansion. Consequently, the NiCoON/NF host delivers a high Coulombic efficiency (98.4% over 600 cycles) at 1 mA cm-2 and an ultralong lifespan (> 2000 h) under a high capacity of 3 mAh cm-2. Remarkably, a Li@NiCoON/NF-LiFePO4 full battery also reveals impressive electrochemical performance. This work demonstrates new insights into safe rechargeable Li metal batteries.

Understanding the complex relationship between active small molecules is of great significance in various physiological processes. Herein, we present the design and synthesis of a sequential responsive Lysosome-Naphthalene imide-Azido (lyso-NP-N3) reporter for probing the H2S and HOBr within organelle (lysosome) in living cells. Probe lyso-NP-N3 exhibited high selectivity and sensitivity towards H2S (LOD = 23.5 nM) and HOBr (LOD = 254 nM). Additionally, lyso-NP-N3 possessed an excellent lysosome targeting ability and was utilized to visualize the exogenous/endogenous H2S and HOBr in RAW 264.7, Hela and HepG2 cells. Facilitated by this sequentially activated mechanism, the probe was successfully applied to confirm that the reported scavenger of HOBr, N-acetyl-L-cysteine (NAC) mainly relied on its metabolite H2S to eliminate excess HOBr, thereby playing the role of cell regulation and protection. These results establish the crosstalk between H2S and HOBr in lysosome and provide a promising tool to study metabolite interactions.

As chloride ions (Cl−) play a vital role in maintaining normal physiological activity, detection of chloride ions is quite urgent. Hence, we developed chloride fluorescence probes to highly selectively and sensitively monitor chloride ions. The probe M2 with single emission has a high fluorescence quantum yield (Φ = 45%), and it is capable of quantitative detection of Cl− under physiological conditions (pH = 7.4) and pH = 5.0 with a linear range of 0.1–4.0 mM; nevertheless, it is of the switch-off type. We further synthesized a ratiometric fluorescent probe MY with M2 as raw material, which featured excellent selectivity and anti-interference, and large two-photon cross section (555 GM). The probe is conveniently used to detect Cl− in water samples and biological samples including human sweat, serum, and urine samples, indicating it holds great promise for chloride detection and biological application.

In chemical processes, it would be much beneficial to develop a technique to precisely predict the standard chemical exergy values of different compounds. In this study, a multi-layer perceptron (M...

Fuel quality, especially biodiesel, is highly dependent on its water content, and the major sources of water in the fuel relate to the transportation, production, and storage processes. In this present contribution, the multilayer perceptron artificial neural network (MLP-ANN) was applied to predict the water content of biodiesel and diesel blend in terms of temperature and composition. The proposed algorithm was trained and tested by utilizing 400 experimental data points which were extracted from the literature. Based on the results, the MLP-ANN model has great ability to estimate the water content of biodiesel and diesel blend. The R-squared (R2), root mean square error, average absolute relative deviation, and a​bsolute deviation parameters for the total data set are obtained, respectively, as 0.99784, 123919.1172, 3.3632, and 1.17%, which indicate the effective performance suggested by ANN. As the computational study is cheaper and easier than the experimental study, the developed software co...

This study investigated the performance of co-digesting cucumber residues, corn stover, and pig manure at different ratios. Microbial community structure was analyzed to elucidate functional microorganism contributing to methane production during co-digestion. Results show that mixing cucumber residues with pig manure and corn stover could significantly improved methane yields 1.27–3.46 times higher than mono-feedstock. The methane yields decreased with the cucumber residues increasing when the pig manure ratio was fixed at 4 and 3, and was opposite at ratio 5. The optimal mixture ratio was T2 with the highest methane yield (305.4 mL/g VS) and co-digestion performance index (1.97). The main microbiological community in T2 was bacteria of Firmicutes (44.6%), Bacteroidetes (32.5%), Synergistetes (3.8%) and archaea of Methanosaeta (37.1%), Methanospirillum (18.2%). The mixture ratios changed the microbial community structures. The adding proportion of cucumber residues changed the community composition of the archaea, especially the proportion of Methanosaeta.

Enhancing the dispersion stability and self-antibacterial properties of cationic waterborne polyurethane materials is of vital importance to its various applications. In this work, a novel UV-curable waterborne polyurethane with pendant amine (PWPU) from 4-NCO prepolymer and modified by guanidinoacetic acid (GAA) was prepared by a simple method. The 4-NCO prepolymer is originated from the progressively grafting of tridentate polycaprolactone. The GAA, which is rarely used in coating industry, plays a positive reinforced role in our self-antibacterial coatings. Taking fully advantage of the merits of pendant amine and GAA, PWPU without bactericides possesses excellent properties in gram-negative (92.05%) and gram-positive (94.77%) antibacterial tests. Compared with the linear amine waterborne polyurethane (LWPU), PWPU has significant superiority in stability, and the increase in antibacterial efficiency is about 50%. Moreover, antibacterial efficiency still maintained 87.94% after 12 times washing. AFM results display that GAA and pendant amine increase the hydrophilic groups of coating surface, which improves the antibacterial performance. The experiments of thermal, mechanical performance and chemical resistance proof the reliability of the coatings. Therefore, this work has large potential in the applications of antibacterial materials.

The monitoring of K+ is very important and emergency because of their unique relationship in various disease diagnosis and treatment. G-quadruplex analogue is a classical recognition unit for K+ detection and has been widely applied in K+ relevant research. Common fluorescent dyes were employed for design of G-quadruplex structure-based K+ probes which suffered from the aggregation-caused quenching effect, and possibly limited the biological applications in living systems. Herein, we report an aggregation-induced emission (AIE) effect-based fluorescent probe for cellular K+ analysis and imaging. Benefitting from the K+ triggered AIE phenomenon, the designed TPE derivative modified guanine (G)-rich oligonucleotide fluorescent probe (TPE-oligonucleotide probe) exhibits high sensitivity (∼10-fold higher than most reported G-quadruplex-based probes) with extended photostability which facilitates the prolonged fluorescence observations of K+ in living cells. On the basis of these advantages, the TPE-oligonucleotide probe serves as a promising candidate for the functional study and analysis of K+.

The KW from Chaoyang District was mainly treated by incineration at present. The main purpose of this study was to analysis whether the properties of kitchen waste (KW) in Chaoyang District, Beijing were appropriate for anaerobic digestion (AD). The KW was obtained from four typical closed cleaning stations by sampling once per quarter. The results showed the classification of four different typical closed cleaning station based on living standard was around 90% with good classification levels except Erdaogou and all featured with high vegetables and peels contents. Variable pH with different typical closed cleaning station and sampling season and was suitable for AD other than composting. The high moisture content (MC) was also not suitable for composting. The indices of C/N ratio (basically ranged in 15–20), EC, and NH4 +–N content were measured and showed the KW could be treated by AD. The properties of KW vary with living standard and seasons. The properties of KW sampled in the same season, but closed cleaning station were different with each other and also sampled in the same closed cleaning station but different seasons varied widely. Finally, (Guoxue Li) considering the particular nature of KW, AD was better disposal than composting for treating KW in Chaoyang District.

The present study was designed to elucidate the key parameters associated with X-ray radiation induced oxidative stress and the effects of STS on X-ray-induced toxicity in H9c2 cardiomyocytes. Cytotoxicity of STS and radiation was assessed by MTT. Antioxidant activity was evaluated by SOD and MDA. Apoptosis was measured by the flow cytometry, Hoechst 33258, clonogenic survival assay, and western blot. It was found that the cell viability of H9c2 cells exposed to X-ray radiation was significantly decreased in a dose-dependent manner and was associated with cell cycle arrest at the G0/G1 phase as well as apoptosis. STS treatment significantly reversed the morphological changes, attenuated radiation-induced apoptosis, and improved the antioxidant activity in the H9c2 cells. STS significantly increased the Bcl-2 and Bcl-2/Bax levels and decreased the Bax and caspase-3 levels, compared with the cells treated with radiation alone. STS treatment also resulted in a significant increase in p38-MAPK activation. STS could protect the cells from X-ray-induced cell cycle arrest, oxidative stress, and apoptosis. Therefore, we suggest the STS could be useful for the treatment of radiation-induced cardiovascular injury.

Mitochondrial calcium uniporter (MCU) has an important role in regulating mitochondrial calcium (Ca2+) homeostasis. Dysregulation of mitochondrial Ca2+ homeostasis has been implicated in various cancers. However, it remains unclear whether MCU regulates mitochondrial Ca2+ uptake to promote cell growth in colorectal cancer (CRC). Therefore, in the present study the expression of MCU in CRC tissues and its clinical significance were examined. Following which, the biological function of MCU-mediated mitochondrial Ca2+ uptake in CRC cell growth and the underlying mechanisms were systematically evaluated using in in vitro and in vivo assays, which included western blotting, cell viability and apoptosis assays, as well as xenograft nude mice models. Our results demonstrated that MCU was markedly upregulated in CRC tissues at both the mRNA and protein levels. Upregulated MCU was associated with poor prognosis in patients with CRC. Our data reported that upregulation of MCU enhanced the mitochondrial Ca2+ uptake to promote mitochondrial biogenesis, which in turn facilitated CRC cell growth in vitro and in vivo. In terms of the underlying mechanism, it was identified that MCU-mediated mitochondrial Ca2+ uptake inhibited the phosphorylation of transcription factor A, mitochondrial (TFAM), and thus enhanced its stability to promote mitochondrial biogenesis. Furthermore, our data indicated that increased mitochondrial Ca2+ uptake led to increased mitochondrial production of ROS via the upregulation of mitochondrial biogenesis, which subsequently activated NF-κB signaling to accelerate CRC growth. In conclusion, the results indicated that MCU-induced mitochondrial Ca2+ uptake promotes mitochondrial biogenesis by suppressing phosphorylation of TFAM, thus contributing to CRC cell growth. Our findings reveal a novel mechanism underlying mitochondrial Ca2+-mediated CRC cell growth and may provide a potential pharmacological target for CRC treatment.

Glutenin is the main protein of flour and is a very important source of protein nutrition for humans. Methylglyoxal (MGO) is an important product of the Maillard reaction that occurs during the hot-processing of flour products, and it reacts with glutenin to facilitate changes in glutenin properties. Here, the effects of MGO on glutenin digestion during the heating process were investigated using a simulated MGO-glutenin system. MGO significantly reduced the digestibility of glutenin. The structure of MGO-glutenin and physicochemical properties were studied to understand the mechanism of the decrease of digestibility. These data suggest that changes in digestibility were caused by decreases in surface hydrophobicity and increases in disulfide bonds. MGO induces strong aggregation of glutenin after heating that led to the masking of cleavage sites for proteases. Moreover, carbonyl oxidation induced by MGO leads to intermolecular cross-linking of glutenin that increasingly masks or even destroys cleavage sites, further decreasing digestibility.

Salt-inducible kinase 2 (SIK2), which belongs to the AMP-activated protein kinase family, modulates various biological functions including fatty acid oxidation. However, the role of SIK2 in glucose metabolism reprogramming remains unclear in ovarian cancer (OC) cells. Here, we found that SIK2 significantly enhanced the Warburg effect of OC cells mainly through two mechanisms. On the one hand, SIK2 upregulated the expression of HIF-1α by activating the PI3K/AKT signaling pathway, which directly upregulated the transcription of major glycolytic genes to promote glycolysis. On the other hand, SIK2 promoted mitochondrial fission through phosphorylation of Drp1 at Ser616 site, which inhibited the mitochondrial oxidative phosphorylation. In addition, SIK2 promoted growth and metastasis of OC cells by promoting cell proliferation and inhibiting cell apoptosis, as well as enhancing the epithelial-mesenchymal transition. Moreover, the SIK2-mediated reprogramming of glucose metabolism played a critical role in growth and metastasis of OC cells. Collectively, our findings demonstrate that SIK2 is a crucial regulator of glucose metabolism in OC cells through activation of PI3K/AKT/HIF-1α pathway and Drp1 phosphorylation-mediated mitochondrial fission, which plays a critical oncogenic role in OC cells.

DNA-loaded molecularly imprinted gelatin nanoparticles (GDMI-NPs) were prepared to deliver the Cy3- and Cy5-labelled DNA probe to a tumor region. This allows the activity of telomerase can be detected over 3-400 cells with a low detection limit (3 cells). Fluorescence images were acquired at an excitation wavelength of 535 nm and the emission from the green channel (550-580 nm; label Cy3) and the red channel (650-680 nm; label Cy5). HeLa cells and HepG2 cells were both used to test the performance of GDMI-NPs. Experimental results confirmed the GDMI-NPs has hardly retained in liver and spleen tissue, and its circulated time was longer than that of non-imprinted nanoparticles in blood. The ability of GDMI-NPs to resist immuno stress and anti-macrophage phagocytosis shows great potential for cancer diagnosis and as a drug carrier. Graphical abstract Highly DNA-loaded molecularly imprinted gelatin nanoparticles (GDMI-NPs) were prepared to deliver the Cy3-labelled DNA probe to a cancer region, and realization of telomerase in situ fluorescence imaging at the tumor site.

Reaction of a scandium phosphoniomethylidene with carbon monoxide provides the first scandium phosphonioketene (1). X-ray diffraction analysis shows that the complex has a very short Sc-C bond (2.138(2) A), and DFT calculations indicate that this unusual short bond length is due to the significant contribution of ionic coulomb interaction between carbon and scandium and the η2 -O,C coordination fashion. Complex 1 is thermally stable, albeit shows high reactivity towards a series of unsaturated substrates, including carbon dioxide, ketone, imine, nitrile and isocyanide. In the reaction with tert-butyl isocyanide, not only an insertion of tert-butyl isocyanide into the Sc-C bond occur, but also a C-H activation on the phenyl ring. DFT calculations show that the reactivity of 1 operated by nucleophilic properties, and therefore the reaction mechanism favors the nucleophilic attack to isocyanide as a rate-determining step, followed by the stepwise C-H activation through an interesting C-H deprotonation.

Installing a ground-based super capacitor energy storage system in the subway will effectively recover the regenerative braking energy of the train, reduce the energy consumption of the system, and achieve the goal of green and environmental protection. Various substations, traction/braking trains and energy storage systems interact in real time through the traction network to form a complex multi-energy coupling system. Therefore, in order to improve the overall energy efficiency of the traction power supply system and reduce investment costs, this article proposes Comprehensive optimization method for power supply system parameters and energy storage system capacity configuration. Through research, it is found that compared to the optimization of a single energy storage system, comprehensive optimization effectively improves the energy-saving rate of the energy storage system when the investment cost is similar.

This paper focuses on the practical application of EPC and RFID technology in the logistics. Internet is the foundation of IoT, it using wireless communications, RFID, computer network technology e...

Due to favourable efficiency and low cost, dual-response fluorescent probes play critical roles in the development of fluorescence assay system. Herein, a novel dual-response fluorescent probe (RDCN) was designed and synthesized for the detection of two environmental contaminants: hydrazine (N2H4) and cyanide (CN−). Probe RDCN exhibited discriminative sensing behaviors to N2H4 and CN− with different reaction mechanisms, allowing the high selectivity and sensitivity detection for N2H4 and CN−. The probe itself displayed red-emitting fluorescence as a result of strong intramolecular charge transfer (ICT) between diethylamino and dicyano. After mixing with hydrazine, a new corresponding hydrazone came into being with an intense yellow fluorescence. While, the probe could also largely switch to blue fluorescence in response to CN−. Furthermore, the probe RDCN was successfully employed to determine N2H4 and CN− in water samples with the detection limits of 0.08 μM and 0.33 μM, and to visualize N2H4 and CN− in live cells by means of different fluorescence channels (blue and yellow channels), revealing that probe RDCN has potential applications for discriminative detection N2H4 and CN− in biological environment.

Uric acid (UA) is an important biomarker in urine and serum samples for early diagnosis. This study re- ports a fluorescent biosensor based on Poly(cytosine)-templated silver nanoclusters (C-Ag NCs) and uricase for the highly sensitive and fast detection of UA. The strong fluorescence of the C-Ag NCs prepared from poly (cytosine) nucleotides templates could be sensitively quenched by trace amount of H2O2, which produced from oxidation reaction of UA catalyzed by uricase. This biosensor exhibits two linear ranges as 50 nM∼50 μM and 50 μM∼400 μM, with a detection limit of 50 nM. The sensitivity of the biosensor is considerably improved compared with the methods reported in the literature. Furthermore, the detection ability of uric acid in serum samples is confirmed and this C-Ag NCs-based uric acid biosensor shows good promise of practical application.

This study analyzed the composition and characteristic of kitchen waste (KW) from closed cleaning station of Chaoyang District, Beijing. It was featured by high vegetables and peels contents. This study investigated effect of pH regulation and uncontrolled pH (CK) on the lab-scale anaerobic hydrolysis acidification stage of KW. The optimal adjusting mode by NaOH (including dosage and frequency) was evaluated according to indexes of pH, VFAs, NH4(+)-N, TS, VS, TS/VS, TS and VS removal rate. The treatment 4 as first two days adjusting per 16h and then one time per day at pH 7 was chosen as the optimal mode with high VFAs content(47.31g/L), TS and VS removal rate (42.95% and 54.01%, respectively), low adjusting frequency, fewer dosage and practical operability. Thus, adjusting mode of treatment 4 could be considered using in anaerobic hydrolysis acidification stage on engineering.

Coal based magnetic activated carbons (MACs) were prepared by using the two-stage carbonization and activation of coal in the presence of Fe2O3 as the magnetic source. Compared with the single-stage carbonization and activation, the two-stage temperature method was found to be efficient for the preparation of MACs with the high specific surface area and good magnetic properties in a lower alkali/carbon ratio. The as-synthesized MACs at optimized conditions exhibited specific surface areas of up to 2075 m2/g and optimal saturation magnetization of as high as 15.02 emu/g. Moreover, as an adsorbent, the efficiency of removing methylene blue (MB) from aqueous solutions is excellent. Based on MB adsorption behaviors at various conditions, including initial dye concentration, contact time and temperature, MACs prepared at optimized conditions exhibited a maximum equilibrium MB adsorption capacity of 871 mg/g. The data of adsorption kinetics and isotherms could be well fitted by using the pseudo-second-order equation and the Freundlich model. Importantly, MACs can be separated and recovered easily by applying a magnetic field. Therefore, the coal-based magnetic activated carbons might be a promising candidate of high efficiency, low cost for removal of organic dyes.

A new trimeric cluster [(SiW9Nb3O38)3MnO3(H2O)3]13− (1) with three Keggin-type trilacunary SiW9 units connected by a {MnNb9} core were structurally characterized. The polyanion 1 features three corner-shared {Nb3O3} fragments that are linked to each other on two sides via three Nb–O–Nb bridges and by a {MnII} linker. To the best of our knowledge, polyanion 1 represents the first example of a trimeric niobotungstate cluster reported to date, and is revealed for the first time uniting a family of polytungstosilicate clusters. The formation of polyanion 1 exemplifies the reactivity of {(NbO2)3SiW9} with a manganese metal ion, defining a new in situ synthetic strategy for {(NbO2)3SiW9}-based derivatives, featuring POM chemistry between Nb/W mixed-addendum POMs and various transition-metal or lanthanide species.

Graphitic carbon nitride (g-C3N4) is normally used in photocatalysis under visible light, to realize its' enhanced electrocatalytic hydrogen evolution reaction is still a challenge. In this paper, superior thin g-C3N4 nanosheets with different composition and crystallinity are prepared via theromal polarization process to test their photo- and electro-chemical activities. Interestingly, a crystalline/amorphous g-C3N4 nanosheet homojunctions are successfully prepared via one-step thermal polymerization by adjusting preparation parameters. Crystalline and amorphous phases are homogeneously distributed in thin g-C3N4 nanosheets. Compared with crystalline and amorphous g-C3N4 nanosheets, the homojunction prepared using optimized C/N ratio and crystalline/amorphous phase distribution reveals the quick photodegradation of dyes. Ni Fe oxides are deposited on g-C3N4 by a further thermal polymerization process. After loading metal oxides, the photo- and electro-catalytic performance of crystalline/amorphous homojunctions is greatly enhanced. Especially, the co-loading of Fe2O3 and NiO drastically enhances the electrochemical performance of g-C3N4 nanosheet homojunctions. Using optimized loading amount, the overpotentials of amorphous g-C3N4 nanosheets, g-C3N4 amorphous/crystalline nanosheet homojunctions, and crystalline g-C3N4 nanosheets are 756, 691 and 672 mV for electrochemical hydrogen evolution reaction with Tafel slope of 101, 79 and 74 mV/dec, respectively.

CD40 stimulation on antigen-presenting cells (APCs) promotes activation of CD8(+) cytotoxic T cells and several CD40 agonistic antibodies have shown promising anti-tumor activities in initial clinical trials. However, agonistic CD40 stimulation also leads to PD-L1 upregulation on APCs, thus creating a negative feedback loop to dampen the anti-tumor immune response. We hypothesized that the combination of PD-L1 antagonism with CD40 agonists would achieve stronger antitumor responses than with anti-CD40 alone. Here we report a novel bispecific antibody MEDI7526, which is composed of an anti-PD-L1 antibody, two trimer forms of CD40 ligand (CD40L) fusion protein (FP) and a human IgG4p Fc. MEDI7526 has been designed to stimulate the CD40 pathway and suppress PD-L1 function to improve T cell activation and potentially overcome the limitations associated with conventional CD40 agonists. The binding characteristics and functional activity of MEDI7526 were analyzed in vitro using flow cytometry and cell-based reporter assays. Internalization of MEDI7526, CD40, and PD-L1 were examined by flow cytometry and immunofluorescence microscopy. Effects of MEDI7526 on cytokine production from human PBMC were analyzed with MSD multiplex assay. Anti-tumor efficacy was determined by a murine surrogate version of MEDI7526 in a B16F10 syngeneic model. We confirmed that MEDI7526 can bind CD40 and PD-L1 simultaneously. MEDI7526 induced robust activation of CD40 signaling and triggered fast internalization of CD40. Interestingly, MEDI7526 also triggered rapid and robust down-regulation of PD-L1 on the cell surface of multiple types of cells that express CD40, including THP1, MDA-MB-231 and human monocytes, whereas PD-L1 expression was not affected by the treatment of either anti-PD-L1 antibody or CD40L FP. Prolonged treatment of MEDI7526 on MDA-MB-231 cells induced sustained down-regulation of PD-L1 for up to 4 days. When THP1 cells were transiently treated with MEDI7526, cell surface CD40 returned after 24 hours but levels of PD-L1 on the cell membrane remained low, indicating re-expression of cell surface CD40 and PD-L1 following distinct pathways. We demonstrated that internalized PD-L1 undergoes lysosome-dependent, proteasome-independent degradation, resulting in sustained down-regulation of PD-L1 from cell surface. Moreover, MEDI7526 induced robust IFNγ production in antigen recall assays, and the murine surrogate of MEDI7526 effectively inhibited tumor growth in the B16F10 syngeneic model. These studies demonstrate that MEDI7526 drives the internalization and degradation of PD-L1 and exhibits robust in vitro and in vivo activities. Building this novel bispecific molecule brings two molecules together, resulting in novel mechanisms of action that are different from combinations of parental reagents. MEDI7526, through its unique function of simultaneously stimulating the CD40 pathway and down-regulating PD-L1 expression, represents a promising therapeutic approach against cancer. Citation Format: Yaya Wang, Sean Turman, Deepali Malhotra, Ryan Gilbreth, Yue Wang. MEDI7526: a novel bispecific antibody that activates the CD40 pathway and down-regulates cell surface PD-L1 expression [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5178.

Background: While diverse strategies may boost anti-tumor immunity, of significant interest are therapeutic approaches that are efficacious in tumors with high and low immune cell infiltration. Targeting CD40 with its natural ligand (CD40L) augments the immune-stimulatory function of antigen-presenting cells and enhances T cell priming, making this an attractive means of promoting anti-tumor responses. MEDI5083 is a novel fusion protein containing a hexameric recombinant human CD40L structure covalently linked to human IgG4p Fc. Here, we present preclinical functional characterization of MEDI5083. Methods MEDI5083 functionality was first established using several in vitro approaches with human cell lines and primary human cells. To examine anti-tumor activity in vivo, we constructed a murine surrogate (mCD40L-Fc) with similar physical and target-binding properties to those of MEDI5083. The effects of mCD40L-Fc on immune cell activation and tumor growth were determined in the immunologically cold B16F10 model of melanoma and the immunologically hot CT26 model of colon carcinoma. Results: MEDI5083 specifically bound to human CD40, triggered its internalization, and robustly stimulated CD40 signaling as measured by NF-κB activation in Ramos and THP-1 cells. MEDI5083 potently upregulated expression of MHCII and the co-stimulatory molecules CD80 and CD86 on primary human B cells and myeloid cells, while inducing secretion of pro-inflammatory cytokines. MEDI5083 also enhanced secretion of IFN-γ by memory CD8+ T cells in an antigen-recall assay. In the B16F10 model, repeated mCD40L-Fc dosing significantly decreased tumor growth. Consistent with enhancing immune cell activation and T cell priming, mCD40L-Fc treatment elevated serum levels of IL-12 and IFN-γ, and increased numbers of tumor-infiltrating CD8+ T cells. While this model responds poorly to checkpoint blockade, co-administration of mCD40L-Fc with anti-PD-L1 antibody demonstrated additivity, consistent with PD-1/PD-L1-mediated regulation of mCD40L-Fc-driven adaptive immunity. Repeated dosing of mCD40L-Fc in the CT26 model inhibited tumor growth. Treatment was associated with diminished tumor-infiltrating Treg numbers, increased CD8+ T cell:Treg ratios, and phenotypic changes in tumor-infiltrating immune cells. Tumor supernatants exhibited increased IFN-γ, consistent with enhanced anti-tumor immunity. Rechallenge of mice with complete tumor regression confirmed generation of durable memory. Conclusions: We have demonstrated that stimulation of CD40 signaling with MEDI5083 or mCD40L-Fc leads to robust activation of immune cells and enhanced adaptive immune responses. In vivo, this translates to enhanced control of both poorly- and well-infiltrated syngeneic tumors and generation of durable memory in mice with complete tumor regression. Citation Format: Deepali Malhotra, Sean Turman, Kelly McGlinchey, Yaya Wang, Yue Wang. MEDI5083, a novel CD40L-Fc fusion protein, activates the CD40 pathway on antigen-presenting cells and promotes robust anti-tumor immune responses in both hot and cold murine tumor models [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2267.

Coarse cereal intake has been reported to be associated with reduced risk of colorectal cancer. However, evidence from intervention studies is absent and the molecular basis of this phenomenon remains largely unexplored. This study sought to investigate the effects of foxtail millet and rice, two common staple grains in Asia, on the progression of colitis-associated colorectal cancer (CAC) and define the mechanism involved. In total, 40 BALB/c mice were randomized into four groups. The Normal and azoxymethane/dextran sodium sulfate (AOM/DSS) groups were supplied with an AIN-93G diet, while the millet- and rice-treated groups were supplied with a modified AIN-93G diet. Compared to the AOM/DSS-induced CAC mice supplemented with rice, an increased survival rate, suppressed tumor burden, and reduced disease activity index were observed in the millet-treated group. The levels of IL-6 and IL-17 were decreased in the millet-treated group compared to both the AOM/DSS and AOM/DSS + rice groups. Millet treatment inhibited the phosphorylation of STAT3 and the related signaling proteins involved in cell proliferation, survival and angiogenesis. These beneficial effects were mediated by the activation of gut receptors AHR and GPCRs via the microbial metabolites (indole derivates and short-chain fatty acids) of foxtail millet. Moreover, millet-treatment increased the abundance of Bifidobacterium and Bacteroidales_S24-7 compared to the rice-treated mice. This study could help researchers to develop better dietary patterns that work against inflammatory bowel disease (IBD) and for CAC patients.

This study investigated the effects of three different intermittent mixing modes (top, middle and bottom) on the performance of solid state anaerobic digestion (SS-AD) process of pig manure, corn stover and cucumber residues in a stirred tank reactor (STR). Results showed the cumulative methane yields of reactors had similar values (P > 0.05) except for the unmixed reactor (CK), which had a very low methane production. Reactors of top-mixed (T1) had shortest technical digestion time (T80) and more stable physicochemical characteristics than the other treatments. These findings indicated the three mixing modes had almost no effect on the cumulative methane yields, but affected the digestion process. The main bacteria in T1 reactor was Clostridium_sensu_stricto_1. However, Caldicoprobacter accounted for a relatively large proportion of the bacteria in middle-mixed (T2) and bottom-mixed (T3) which was consistent with the later methane production than T1. Methanosarcina was the dominant archaea in T1 reactor. Methanoculleus and Methanosarcina were the main microorganisms in top and bottom area of T2 and T3 reactor. Acidogenic (top area) and methanogenic zones (bottom area) were formed in all reactors respectively, by combining the physicochemical properties and microorganisms. Overall, T1 showed more advantages for methane production during SS-AD.

Cyanobacteria always massively grow and even occur blooms in summer, with releasing amount of β-cyclocitral. To uncover the effects of summer high irradiance and temperature on cyanobacterial growth and β-cyclocitral emission, the cell growth, reactive oxygen species (ROS) levels, photosynthetic pigment content, chlorophyll fluorescence and β-cyclocitral emission were investigated in Microcystis aeruginosa under high light and temperature. Compared to the control under 50 μmol m−2·s−1, the cell growth was promoted under 100 μmol m−2·s−1, but inhibited under 500 and 1000 μmol m−2·s−1. The inhibition was also detected under high temperature at 30 and 35 °C in contrast to the control at 25 °C. Under high light and high temperature, M. aeruginosa increased ROS levels and reduced photosynthetic pigment content and photosystem II (PSII) efficiency, which resulted in the inhibition on cell growth. With increasing the light intensity and temperature, 1O2 levels gradually increased, while β-carotene content gradually decreased by quenching 1O2, with increasing β-cyclocitral emission. In summer, high irradiance and temperature not benefited the growth of cyanobacteria, but the emission of β-cyclocitral derived from β-carotene quenching 1O2 may offset the disadvantages by poisoning other algae.

Increasing atmospheric nitrogen (N) deposition could profoundly impact soil carbon, N and phosphorus cycling that are often regulated by extracellular enzymes. The potential activities of enzymes in response to N deposition have been studied extensively, but the kinetic mechanisms in response to canopy and understory N additions in different soil layers are poorly understood. Here, we conducted a six-year-long field manipulation experiment in a temperate deciduous forest to reveal the kinetic characteristics of seven extracellular hydrolytic enzymes in the litter, organic and mineral soil layers in response to canopy and understory N additions. Canopy N addition and understory N addition exerted similar effects on the kinetics parameters (Vmax and Km) of most enzymes under study. The kinetics parameters of most enzymes generally increased in the litter layer but decreased in the organic layer and had little change in the mineral soil layer in response to N addition. In addition, the changed kinetic parameters were mainly correlated with moisture in the litter layer, with pH, substrate properties (TC, TN, DOC and DON) and microbial communities (G+, G-, total bacterial and fungal biomass) in the organic and mineral soil layers. These findings indicate that enzyme kinetics responses to N deposition differ in soil layers with varying determinant factors, and therefore are driven by various physical, chemical and microbial mechanisms.

Correction for ‘Nitrogen-doped carbon nanotubes as an anode for a highly robust potassium-ion hybrid capacitor’ by Xiuqi Li et al., Nanoscale Horiz., 2020, DOI: 10.1039/d0nh00451k.

Agricultural ecosystems are major sources of greenhouse gas (GHG) emissions, specifically nitrous oxide (N2O) and carbon dioxide (CO2). An important method of investigating GHG emissions in agricultural ecosystems is model simulation. Field measurements quantifying N2O and CO2 fluxes were taken in a summer maize ecosystem in Zhangye City, Gansu Province, in northwestern China in 2010. Observed N2O and CO2 fluxes were used for validating flux predictions by a DeNitrification-DeComposition (DNDC) model. Then sensitivity tests on the validated DNDC model were carried out on three variables: climatic factors, soil properties and agricultural management. Results indicated that: (1) the factors that N2O emissions were sensitive to included nitrogen fertilizer application rate, manure amendment and residue return rate; (2) CO2 emission increased with increasing manure amendment, residue return rate and initial soil organic carbon (SOC); and (3) net global warming potential (GWP) increased with increasing N fertilizer application rate and decreased with manure amendment, residue return rate and precipitation increase. Simulation of the long-term impact on SOC, N2O and net GWP emissions over 100 yr of management led to the conclusion that increasing residue return rate is a more efficient method of mitigating GHG emission than increasing fertilizer N application rate in the study area.

As one of the most widespread anions, chloride ion largely existed in the water sources as well as living organism. Therefore, determination of chloride ions in biological samples is evidently important. Herein, we developed two analogous fluorescence probes BeQ1 and BeQ2 for the sensitive detection of chloride ions. The chloride ions in biological samples were determined by a direct and simple method with the detection limit of 46 and 66 μM respectively. In addition, the probes were found having the two-photon excitation property.