Amphiregulin secreted by umbilical cord Multipotent Stromal Cells protects against ferroptosis of macrophages via the Activating Transcription Factor 3-CD36 axis to alleviate endometrial fibrosis.

Endometrium fibrosis is the leading cause of uterine infertility. Macrophages participated in the occurrence and development of endometrial fibrosis. We previously reported that human umbilical cord multipotent stromal cells (hUC-MSCs) exerted their therapeutic effect in a macrophage-dependent manner in endometrial fibrosis. However precise mechanisms by which hUC-MSCs may influence macrophages in endometrial fibrosis remain largely unexplored. Here, we demonstrated that abnormal iron and lipid metabolism occurred in intrauterine adhesions (IUA) patients and murine models. Ferroptosis has been proven to contribute to the progression of fibrotic diseases. Our results revealed that pharmacological activation of ferroptosis by Erastin aggravated endometrial fibrosis, while inhibition of ferroptosis by Ferrostatin-1 ameliorated endometrial fibrosis in vivo. Moreover, ferroptosis of macrophages was significantly upregulated in endometria of IUA murine models. Of note, transcriptome profiles revealed that CD36 gene expression was significantly increased in IUA patients and immunofluorescence analysis showed CD36 protein was mainly located in macrophages. Silencing CD36 in macrophages could reverse cell ferroptosis. Dual luciferase reporter assay revealed that CD36 was the direct target of activation transcription factor 3 (ATF3). Furthermore, through establishing coculture system and IUA murine models, we found that hUC-MSCs had a protective role against macrophage ferroptosis and alleviated endometrial fibrosis related to decreased CD36 and ATF3. The effect of hUC-MSCs on macrophage ferroptosis was attributed to the upregulation of amphiregulin (AREG). Our data highlighted that macrophage ferroptosis occurred in endometrial fibrosis via the ATF3-CD36 pathway and hUC-MSCs protected against macrophage ferroptosis to alleviate endometrial fibrosis via secreting AREG. These findings provided a potential target for therapeutic implications of endometrial fibrosis.

Induction Chemotherapy Followed by Radiotherapy versus Concurrent Chemoradiotherapy in elderly patients with nasopharyngeal carcinoma: finding from a propensity-matched analysis.

BACKGROUND: To date, no guideline is proposed for elderly nasopharyngeal carcinoma (NPC) due to lack of prospective clinical trials. The present study comparing the survivals and toxicities in elderly NPC patients received either induction chemotherapy followed by radiotherapy(IC + RT) or concurrent chemoradiotherapy (CCRT) was therefore undertaken to provide a more accurate basis for future clinical practice. METHODS: The eligible elderly NPC patients were retrospectively enrolled. Propensity score matching generated a matched cohort (1:2) composed from CCRT and IC + RT groups. The survivals and treatment-induced toxicities were compared between two groups. Multivariable analysis was carried to identify significant prognostic factors. RESULTS: The 5-year overall survival, cancer-specific survival, locoregional failure-free survival, distant failure-free survival for all patients were 58.3 %, 62.7 %, 88.7 %, 83.0 %, respectively. No significant survival differences were found between CCRT and IC + RT groups in the propensity-matched cohort. In comparison with the patients who received IC + RT, patients who underwent CCRT were associated with more severe acute toxicities including leucopenia (30 % vs. 6.8 %, P = 0.005), anemia (20 % vs. 4.1 %, P = 0.027), mucositis (63.3 % vs. 34.2 %, P = 0.007), weight loss (23.4 % vs. 4.1 %, P = 0.009). Basicranial bone involvement was an independent prognostic factor that predicted all-cause death (HR = 0.553, 95 % CI 0.329-0.929; P = 0.025) and cancer specific death (HR = 0.558, 95 % CI 0.321-0.969; P = 0.038) in elderly patients. CONCLUSIONS: In the context of no guideline for elderly NPC, the present study suggested IC + RT should be a preferable modality compared with CCRT, with similar treatment outcomes but less acute toxicities.

Prediction of MSW pyrolysis products based on a deep artificial neural network.

Pyrolysis is a promising method for recovering resources and energy products from municipal solid waste (MSW). Predicting MSW pyrolysis products is crucial for establishing an efficient pyrolysis system for resource recovery. In this study, a database was established based on MySQL to record relevant information on MSW pyrolysis, which includes the MSW ultimate analysis results, proximate analysis results, parameters of pyrolysis operation and yields of pyrolysis products, etc. Based on the database and with help of a deep artificial neural network (ANN) which contains 10 hidden layers, a prediction model was successfully established to predict the yield of char, liquid and gas products from MSW pyrolysis. The results showed that the coefficients of determination for predicting the yields of char, liquid and gas from the MSW pyrolysis are 0.841, 0.84, and 0.85, respectively; these values demonstrate an accuracy comparable to that achieved for product prediction from single biomass, indicating a successful model performance. The results also show that ash content and temperature are the most important input factors influencing the outputs, namely, yields of char, liquid and gas. The results of this study can help to achieve a more efficient design of the pyrolysis system and improve the recovery of the desired pyrolysis products.

MSCs promote the efferocytosis of large peritoneal macrophages to eliminate ferroptotic monocytes/macrophages in the injured endometria.

BACKGROUND: Endometria are one of the important components of the uterus, which is located in the peritoneal cavity. Endometrial injury usually leads to intrauterine adhesions (IUA), accompanied by inflammation and cell death. We previously reported that both the endometrial ferroptosis was increased and monocytes/macrophages were involved in endometrial injury of IUA. Large peritoneal macrophages (LPMs) are recently reported to migrate into the injured tissues and phagocytose dead cells to repair the tissues. We previously demonstrated that mesenchymal stromal cells (MSCs) had made excellent progress in the repair of endometrial injury. However, it is unclear whether MSCs regulate the LPM efferocytosis against ferroptotic monocytes/macrophages in the injured endometria. METHODS: Here, endometrial injury in IUA mouse model was conducted by uterine curettage and LPS injection surgery and the samples were collected at different times to detect the changes of LPMs and ferroptotic monocytes/macrophages. We conducted LPMs depletion assay in vivo and LPMs and Erastin-induced ferroptotic THP-1 cells coculture systems in vitro to detect the LPM efferocytosis against ferroptotic monocytes/macrophages. The IUA model was treated with MSCs, and their effects on LPMs and endometrial repair were analyzed. Flow cytometry, western blotting, quantitative real-time PCR, immunohistochemical analysis, ELISA, and RNA-sequencing were performed. RESULTS: We found that LPMs migrated to the injured uteri in response to the damage in early phase (3 h), and sustained to a later stage (7 days). Astonishingly, we found that ferroptotic monocytes/macrophages were significantly increased in the injured uteri since 12 h after injury. Moreover, LPMs cocultured with Erastin-induced ferroptotic THP-1 cells in vitro, efferocytosis of LPMs against ferroptotic monocytes/macrophages was emerged. The mRNA expression profiles revealed that LPM efferocytosis against ferroptotic monocytes/macrophages was an induction of glycolysis program and depended on the PPARγ-HK2 pathway. Importantly, we validated that MSCs promoted the efferocytic capability and migration of LPMs to the injured uteri via secreting stanniocalcin-1 (STC-1). CONCLUSION: The data collectively demonstrated first the roles of LPMs via removal of ferroptotic monocytes/macrophages and provided a novel mechanism of MSCs in repairing the endometrial injury.

Lewis Acid Driving Asymmetric Interfacial Electron Distribution to Stabilize Active Species for Efficient Neutral Water Oxidation.

Neutral oxygen evolution reaction (OER) with unique reactive environments exhibits extremely slow reaction kinetics, posing significant challenges in the design of catalysts. Herein, a built-in electric field between the tungstate (Ni-FeWO4 ) with adjustable work function and Lewis acid WO3 is elaborately constructed to regulate asymmetric interfacial electron distribution, which promotes electron accumulation of Fe sites in the tungstate. This decelerates the rapid dissolution of Fe under the OER potentials, thereby retaining the active hydroxyl oxide with the optimized OER reaction pathway. Meanwhile, Lewis acid WO3 enhances hydroxyl adsorption near the electrode surface to improve mass transfer. As expected, the optimized Ni-FeWO4 @WO3 /NF self-supporting electrode achieves a low overpotential of 235 mV at 10 mA cm-2 in neutral media and maintains stable operation for 200 h. Furthermore, the membrane electrode assembly constructed by such self-supporting electrode exhibits robust stability for 250 h during neutral seawater electrolysis. This work deepens the understanding of the reconstruction of OER catalysts in neutral environments and paves the way for development of the energy conversion technologies.

Oroxylin A-induced Trained Immunity Promotes LC3-associated Phagocytosis in Macrophage in Protecting Mice Against Sepsis.

Sepsis is defined as a dysregulated host response to infection that leads to multiorgan failure. Innate immune memory, i.e., "trained immunity", can result in stronger immune responses and provide protection against various infections. Many biological agents, including ß-glucan, can induce trained immunity, but these stimuli may cause uncontrolled inflammation. Oroxylin A (OA) is an active flavonoid compound that is derived from Scutellaria baicalensis. OA is an agonist for inducing trained immunity in vivo and in vitro, and ß-glucan was used as a positive control. The protective effects of OA-induced trained immunity were evaluated in mouse models that were established by either lipopolysaccharide (LPS) administration or caecal ligation and puncture (CLP). The expression of inflammatory factors and signaling pathway components involved in trained immunity was evaluated in vitro using qRT‒PCR, western blotting (WB) and enzyme-linked immunosorbent assay (ELISA). Flow cytometry and confocal microscopy were used to examine reactive oxygen species (ROS) levels and phagocytosis in trained macrophages. A PCR array was used to screen genes that were differentially expressed in trained macrophages. Here, we revealed that OA alleviated sepsis via trained immunity. OA-treated macrophages displayed increased glycolysis and mTOR phosphorylation, and mTOR inhibitors suppressed OA-induced trained immunity by effectively reprogramming macrophages. The PCR array revealed key genes in the mTOR signaling pathway in OA-treated macrophages. Furthermore, OA targeted the Dectin-1-syk axis to promote LC3-associated phagocytosis (LAP) by trained macrophages, thereby enhancing the ability of these macrophages to protect against infection. This ability could be transferred to a new host via the adoptive transfer of peritoneal macrophages. This study is the first to provide new insights into the potential of OA-induced trained immunity to be used as a strategy to protect mice against sepsis by promoting LAP by macrophages.

Inflammation and cancer: paradoxical roles in tumorigenesis and implications in immunotherapies.

Chronic inflammation caused by persistent infections and metabolic disorders is thought to contribute to the increased cancer risk and the accelerated cancer progression. Oppositely, acute inflammation induced by bacteria-based vaccines or that is occurring after cancer selectively inhibits cancer progression and metastasis. However, the interaction between inflammation and cancer may be more complex than the current explanations for the relationship between chronic and acute inflammation and cancer. In this review, we described the impact of inflammation on cancer on the basis of three perspectives, including inflammation with different durations (chronic and acute inflammation), different scopes (systemic and local inflammation) and different occurrence sequences (inflammation occurring after and before cancer). In addition, we also introduced bacteria/virus-based cancer immunotherapies. We perceive that inflammation may be a double-edged sword with cancer-promoting and cancer-suppressing functions in certain cases. We expect to further improve the understanding of the relationship between inflammation and cancer and provide a theoretical basis for further research on their complex interaction.

Manipulating electron redistribution induced by asymmetric coordination for electrocatalytic water oxidation at a high current density.

Electronic structure manipulation with regard to active site coordination is an effective strategy to improve the electrocatalytic oxygen evolution reaction (OER) activity. Herein, we present the structure-activity relationship between oxygen-atom-mediated electron rearrangement and active site coordination asymmetry. Ni2+ ions are introduced to FeWO4 on Ni foam (NF) via self-substitution to break the symmetry of the FeO6 octahedron and regulate d-electron structure of Fe sites. Structural regulation optimizes the adsorption energy of hydroxyl on the Fe sites and promotes the partial formation of hydroxyl oxide with high OER activity on the tungstate surface. Fe0.53Ni0.47WO4/NF with the asymmetric FeO6 octahedron of Fe sites can achieve an ultralow overpotential of 170 mV at 10 mA cm-2 and 240 mV at 1000 mA cm-2 with robust stability for 500 h at high current density under alkaline conditions. This research develops novel electrocatalysts with impressive OER performance and provides new insights into the design of highly active catalytic systems.

MSW pyrolysis volatiles' reforming by incineration fly ash for both pyrolysis products upgrading and fly ash stabilization.

The effective disposal of municipal solid wastes (MSW) and its incineration-derived fly ash (IFA), which contains large amounts of heavy metals (HMs) and chlorine (Cl), is an urgent task. In this study, IFA was used to reform MSW pyrolysis volatiles within 500-800 °C. The changes of reformed pyrolysis products, the migration characteristics of HMs and Cl between IFA and pyrolysis products were investigated. The results indicated that the O- and Cl-containing compounds in pyrolysis oil tended to decrease, light hydrocarbons and its calorific value increased accordingly after reforming; more CH4 and H2 gases were produced concurrently. The increase in reforming temperature enhanced these trends. The IFA absorbed Cl from volatiles during reforming, which reduced HCl in the gas product. The toxicity equivalent (TEQ) of PCDD/Fs in IFA decreased dramatically from 0.47 µg/kg to 0.0055 µg/kg after reforming at 500 °C, and it decreased with increasing reforming temperature. Some of the HMs' concentrations in the used IFAs increased, but their leaching capacity all decreased significantly at 800 °C except for Cr. The used IFA at 800 °C (IFA-800) corresponded to the lowest HMs leaching concentrations and could meet the landfill requirements; while the used IFA at 500 °C (IFA-500) corresponded to the maximum carbon deposition of 14.63 wt%, providing the energy source for its melting. Therefore 800 °C was recommended for harmless disposal of IFA, and 500 °C was better for a further melting of IFA., The contamination of pyrolysis liquid caused by inorganic Cl-containing compounds at 500 and 800 °C with much lower levels than the original. This study showed the hazardous properties of IFA can be dampened after interacting with MSW pyrolysis volatiles within the tested temperature range, and provided a good chance for the simultaneous disposal of IFA and recovery of high-quality MSW pyrolysis products.

Oroxylin A relieves intrauterine adhesion in mice through inhibiting macrophage pyroptosis via SIRT3-SOD2-ROS pathway.

Intrauterine adhesion (IUA) is manifested by endometrial fibrosis and inflammation, which seriously affects female reproductive health. Macrophages are mainly inflammatory cells and have been reported to participate in the fibrosis of IUA. Oroxylin A (OA), a kind of flavonoid compounds, was showed to possess the inhibitory effects on inflammation and fibrosis. However, the role of OA in IUA remains unclear. In the present study, we found that OA effectively alleviated the level of inflammation and uterine fibrosis in IUA mice. OA also decreased the macrophage pyroptosis which increased in uteri of IUA mice. Pyroptosis is a programmed cell death accompanied by an inflammatory response. Moreover, OA repressed the mediators of pyroptosis including the expression of NOD-like receptor family pyrin domain containing 3 (NLRP3), caspase-1 and Gasdermin D (GSDMD) and the release of IL-1ß, IL-18 and cleaved-caspase-1 in J774A.1 cells induced by LPS/ATP in vitro. Mechanistically, the alleviation of OA on uterine fibrosis is achieved by inhibiting macrophage pyroptosis via SIRT3-SOD2-ROS pathway. Our data indicate that OA may serve as an effective agent for the treatment of the endometrial fibrosis with IUA.

Adsorption of pyrolysis oil model compound (phenol) with plasma-modified hydro-chars and mechanism exploration.

Phenol is one of the important ingredients of pyrolysis oil, contributing to the high biotoxicity of pyrolysis oil. To promote the degradation and conversion of phenol during anaerobic digestion, cheap hydro-chars with high phenol adsorption capacity were produced. The phenol adsorption capabilities of the plain hydro-char, plasma modified hydro-char at 25 °C (HC-NH3-P-25) and 500 °C (HC-NH3-P-500) were evaluated, and their adsorption kinetics and thermodynamics were explored. Experimental results indicate that the phenol adsorption capability of HC-NH3-P-500 was the highest. The phenol adsorption kinetics of all samples followed the pseudo-second-order equation and interparticle diffusion model, indicating that the adsorption rate of phenol was controlled by interparticle diffusion and chemistry adsorption simultaneously. By DFT calculations, π-π stacking and hydrogen bond are the main interactions for phenol adsorption. It was observed that an enriched graphite N content decreased the average vertical distance between hydro-chars and phenol in π-π stacking complex, from 3.5120 to 3.4532 Å, causing an increase in the negative adsorption energy between phenol and hydro-char from 13.9330 to 23.4181 kJ/mol. For hydrogen bond complex, the average vertical distance decreased from 3.4885 to 3.3386 Å due to the increase in graphite N content; causing the corresponding negative adsorption energy increased from 19.0233 to 19.9517 kJ/mol. Additionally, the presence of graphite N in the hydro-char created a positive diffusion region and enhanced the electron density between hydro-char and phenol. Analyses suggest that enriched graphite N contributed to the adsorption complex stability, resulting in an improved phenol adsorption capacity.

Numerical simulation of heat transfer properties of large-sized biomass particles during pyrolysis process.

During the pyrolysis process of large particles, the conduction between particles cannot be ignored. In the present work, a numerical simulation model for the pyrolysis of biomass particles was established, which takes into account the conduction within the particles. Based on this model, the temperature distribution inside the particle during the pyrolysis process was determined and the effects of particle size, moisture content, and gas velocity on heat transfer characteristics were analyzed. The results showed that the temperatures at different positions of the particles along the inflow direction were quite different, and the maximum temperature difference inside the particles was about 146.7 K for a particle diameter of 10 mm and a velocity of 0.2 m/s. During the pyrolysis process of biomass particles, there were two peaks of Nusselt number. The increase of moisture content prolonged the pyrolysis time. The pyrolysis. time of particles with moisture content of 15 % was about 1.5 times longer than that of dry particles when the particle diameter was 10 mm. Increasing the particle size decreased the difference between the two peaks and increased the time interval between the two peaks. Increasing the gas velocity can improve the heat transfer, but the effect of too high gas velocity on improving the heat transfer is limited. The present study is of great importance for a detailed understanding of the pyrolysis process of biomass particles.

Functional diversity of bitter taste receptor TAS2R16 in primates.

In mammals, bitter taste is mediated by TAS2R genes, which belong to the large family of seven transmembrane G protein-coupled receptors. Because TAS2Rs are directly involved in the interaction between mammals and their dietary sources, it is likely that these genes evolved to reflect species-specific diets during mammalian evolution. Here, we investigated the sensitivities of TAS2R16s of various primates by using a cultured cell expression system, and found that the sensitivity of each primate species varied according to the ligand. Especially, the sensitivity of TAS2R16 of Japanese macaques to salicin was much lower than that of human TAS2R16, which was supported by behavioural tests. These results suggest the possibility that bitter-taste sensitivities evolved independently by replacing specific amino acid residues of TAS2Rs in different primate species to adapt to food items they use.

Municipal solid wastes pyro-gasification using high-temperature flue gas as heating resource and gasifying agent.

With the implementation of municipal solid wastes (MSW) source segregation collection policy, the combustible waste components are suitable for pyrolysis treatment to recover value-added energy such as gas or oil. In this research, the volatile compounds from MSW pyrolysis were reformed by the char obtained from the same process and the high-temperature flue gas (HTFG) of 1200 °C was supplying as heating resource and gasifying agent in a tailor-made experimental set-up. The final yields and properties of the syngas, char, and oil after reforming were investigated. Experimental studies showed that the composition of HTFG had a significant influence on the products. As the HTFG being CO2 and its flowrate increased from 0 to 4 L/min/(kgMSW), the energy share in the gas first increased from 8.29 to 15.1 MJ/(kgMSW) with a higher heat value (HHV) of 19.9 MJ/Nm3, then it decreased slightly with a further increase in the flowrate. However, as the HTFG was H2O or the model flue gas (consisting of CO2, H2O, O2 and N2), the higher flowrate always increased the energy share and cold gasification efficiency (CGE) in the gas products. Both CO2 and H2O participated the volatiles' reforming reactions and enhanced char gasification; while the volatiles' reforming inhibited char gasification. When the flowrate of the model flue gas increased from 0 to 12.04 L/min/(kgMSW), the oil and char yields decreased and the CGE increased to more than 75%, which was much higher than that from direct air gasification of MSW; moreover, the gas products had much higher HHVs. This research provides a guidance for producing high-quality syngas from the MSW.

LS-007 inhibits melanoma growth via inducing apoptosis and cell cycle arrest and regulating macrophage polarization.

LS-007, an inhibitor of cyclin-dependent kinase 9 (CDK9), exhibits potential antitumor activity against chronic lymphocytic leukemia and ovarian cancer, but its effect on melanoma and tumor microenvironment (TME) has not been reported yet. This study aimed to investigate the role of LS-007 in B16F10 melanoma and relevant mechanisms. LS-007 significantly inhibited viability and induced apoptosis of B16F10 cells in a dose-dependent manner, which were accompanied with the increased ratio of Bax to Bcl-2 and decreased Mcl-1 mRNA level. Western blot analysis showed that LS-007 increased the expression of cleaved caspase-3 and poly ADP-ribose polymerase (PARP). Furthermore, flow cytometry analysis and qRT-PCR results showed that LS-007 treatment resulted in cell cycle arrest by changing cell cycle-related gene expression. Notably, in vivo evaluation showed that LS-007 significantly decreased the weight and volume of tumor and the expression of Ki67, promoted the expression of iNOS and inhibited the expression of CD206, suggesting that LS-007 might inhibit tumor growth by suppressing polarization of macrophages into tumor-associated macrophages (TAMs) in the TME. The increase in M1/M2 treated with LS-007 detected by flow cytometry hinted that macrophages were polarized towards an antitumor phenotype. In addition, LS-007 induced higher apoptotic rate of B16F10 cells when co-cultured B16F10 with BMDMs. LS-007 has inhibitory effects on B16F10 cells in vivo and in vitro via inducing apoptosis, cell cycle arrest, and changing macrophage function in the TME.

SPECT findings on neuropsychiatric symptoms caused by nitrous oxide abuse.

Objective: The aim of the study was to investigate the clinical, neuropsychological, and regional cerebral blood flow (rCBF) perfusion changes in patients with neuropsychiatric symptoms caused by nitrous oxide (N2O) abuse. Methods: A total of 16 patients with neuropsychiatric symptoms caused by nitrous oxide abuse were recruited for this study. The study was carried out in the withdrawal phase of N2O abuse. A 925-1110 MBq 99mTc-ECD was administered intravenously. SPECT/CT images were collected with a low-energy and high-resolution collimator. The region uptake statistics of different brain regions of interest between patients with N2O abuse and normal people of the databases for younger subjects from the Scenium DB Comparison software were calculated automatically. Results: The clinical manifestations of the 16 patients with neuropsychiatric symptoms were mood lability, anxiety, hallucination, delusion, agitation, confusion, and other psychiatric symptoms. In addition, 15 of the patients also complained of memory decline; 14 patients manifested numbness or paresthesia; 14 patients developed limb weakness, and their motor impairments were more severe in the lower limbs than in the upper limbs; and eight patients had urinary and defecation disturbances. In the neuropsychological examination, the BPRS score was 54.69 ± 11.48, the HAMD score was 30.00 ± 11.06, the HAMA score was 18.06 ± 5.77, the MMSE score was 28.06 ± 2.29, and the MoCA score was 25.06 ± 3.40. SPECT showed hypoperfusion in the frontal and temporal lobes, which is consistent with the clinical findings. Conclusion: This was the first study to demonstrate the obvious effect of N2O abuse on CBF in patients with neuropsychiatric symptoms. CBF perfusion imaging is helpful to detect the changes in the local brain functional activity in patients with N2O abuse.

A video-aided study of the diet of wild white-headed Langurs (Trachypithecus leucocephalus).

Asian leaf-eating monkeys have flexible, environmentally adaptable feeding strategies. The diet and food choices of white-headed langurs (Trachypithecus leucocephalus) have, however, not yet been studied in the Nongguan Karst Hills in China, where one of the two main surviving populations of this endangered species lives. From 2000 to 2002 inclusive, we adopted an innovative video playback analysis method to identify the food species used by the langurs and to calculate the corresponding feeding frequency for each species. The video-aided methodology was shown to be efficient. It provided high-quality images, and the plant species could be identified in 98.3% of the feeding records. Based on this analysis, we found that the langurs in Nongguan fed on 70 species of plants, among which 24 were identified as their staple food species. The cumulative curve for the staple food species reached a plateau at 255 (43.7%) feeding records. This result indicated that most of the langurs' staple food species had been identified by the analysis.

Chitosan-Poly(Acrylic Acid) Nanoparticles Loaded with R848 and MnCl2 Inhibit Melanoma via Regulating Macrophage Polarization and Dendritic Cell Maturation.

PURPOSE: Since immune cells in the tumor microenvironment (TME) can affect the development and progression of tumors, strategies modulating immune cells are considered to have an important therapeutic effect. As a TLR7/8 agonist, R848 effectively activates the innate immune cells to exert an anti-tumor effect. Mn2+ has been reported to strongly promote the maturation of antigen-presenting cells (APCs), thereby enhancing the cytotoxicity of CD8+ T cells. Thus, we tried to investigate whether chitosan-poly(acrylic acid) nanoparticles (CS-PAA NPs) loaded with R848 and MnCl2 (R-M@CS-PAA NPs) could exert an anti-tumor effect by regulating the function of immune cells. METHODS: R-M@CS-PAA NPs were prepared, and their basic characteristics, anti-tumor effect, and potential mechanisms were explored both in vitro and in vivo. RESULTS: R-M@CS-PAA NPs easily released MnCl2 and R848 at low pH. In B16F10 mouse melanoma model, R-M@CS-PAA NPs exerted the most significant anti-melanoma effect compared with the control group and CS-PAA NPs loaded with R848 or MnCl2 alone. FITC-labeled R-M@CS-PAA NPs were displayed to be accumulated at the tumor site. R-M@CS-PAA NPs significantly increased the infiltration of M1 macrophages and CD8+ T cells but reduced the number of suppressive immune cells in the TME. Moreover, in vitro experiments showed that R-M@CS-PAA NPs polarized macrophages into the M1 phenotype to inhibit the proliferation of B16F10 cells. R-M@CS-PAA NPs also enhanced the killing function of CD8+ T cells to B16F10 cells. Of note, R-M@CS-PAA NPs not only promoted the maturation of APCs such as dendritic cells and macrophages by STING and NF-кB pathways, but also enhanced the ability of dendritic cells to present ovalbumin to OT-I CD8+ T cells to enhance the cytotoxicity of OT-I CD8+ T cells to ovalbumin-expressing B16F10 cells. CONCLUSION: These data indicate that the administration of R-M@CS-PAA NPs is an effective therapeutic strategy against melanoma.

B7DC/PDL2 promotes tumor immunity by a PD-1-independent mechanism.

B7H1 (PDL1) and B7DC (PDL2) are two new members of the B7 family that can interact with PD-1, a putative negative regulator for immune function. Recent studies have provided evidence for inhibitory functions of both members via PD-1. Meanwhile, compelling evidence exists for costimulatory function of both members. Here we demonstrate that expression of B7DC on the tumor cells promotes CD8 T cell-mediated rejection of tumor cells, at both the induction and effector phase of antitumor immunity. Moreover, B7DC binds to PD-1(-/-) cells and enhances T cell killing in a PD-1-independent mechanism. Our results demonstrate a novel pathway for B7DC to promote tumor immunity and may reconcile the apparently contradictory findings on the function of B7DC.

Upgrading gas and oil products of the municipal solid waste pyrolysis process by exploiting in-situ interactions between the volatile compounds and the char.

The gas and oil product derived from municipal solid waste (MSW) pyrolysis was upgraded by utilizing the interaction between the volatile compounds and the char and the mechanism involved is explored. The influences of operation parameters, including interaction temperature, char/volatiles mass ratio (C/V) and gas hourly space velocity (GHSV) of the volatiles on the distribution and property of the upgraded products were investigated. The results showed that the higher interaction temperature, higher C/V and lower GHSV favored the conversion of condensable volatiles into gas products, thus increasing the gas yield in the outlet stream. The highest gas yield (44.14 wt%) was obtained at 700 °C with the natural C/V ratio (0.8) and GHSV, which was twice of the gas yield in the volatiles. The chemical energy portion of gas increased to 8065 kJ/kgMSW from 3209 kJ/kgMSW at this condition. Syngas with H2/CO molar ratio of around 2 can be obtained at 700 °C with C/V ratio of 0.8 or at 600 °C with higher C/V ratios (C/V = 1.5-2.2). Oxygenates and acidity of the reformed oil products decreased; but monoaromatics and light polyaromatics concentration increased greatly. Heavy polycyclic aromatic hydrocarbons (PAHs) in the liquid products were degraded after volatiles/hot char interaction. Suitable conditions can be varied and recommended for obtaining different desired high-quality products based on this process.