Experimental study on integrated desulfurization and denitrification of low-temperature flue gas by oxidation method.

In this paper, TiO2 catalysts doped with different Fe contents (Fe-TiO2 catalysts) were prepared by coprecipitation method and the Fe loading capacity was optimized, and then the integrated pollutant removal experiment was conducted, in which TiO2 doped with Fe as catalyst and H2O2 as oxidant. The results show that under the condition of constant H2O2/(SO2 + NO) molar ratio, low concentration of SO2 can promote the oxidation and removal efficiency of NO, while high concentration of SO2 can inhibit the removal of NOx. The pollutant removal efficiency is proportional to the amount of catalyst, liquid-gas ratio and pH value of the absorbing solution. The optimal experimental conditions are H2O2/(SO2 + NO) molar ratio 1.5, space velocity ratio 10,000 h-1, H2O2 mass fraction 10 wt%, liquid gas ratio 10, pH 10. Correspondingly, NO oxidation efficiency reaches 88%, NOx removal efficiency 85.6%, and SO2 is almost completely removed. The microstructure of the catalyst before and after the reaction was characterized, and the crystal structure did not change obviously. However, with the deepening of the reaction, the specific surface area of the catalyst decreases, and the catalytic effect decreases slightly.

Discovery of galectin-8 as an LILRB4 ligand driving M-MDSCs defines a class of antibodies to fight solid tumors.

LILRB4 is an immunosuppressive receptor, and its targeting drugs are undergoing multiple preclinical and clinical trials. Currently, the absence of a functional LILRB4 ligand in solid tumors not only limits the strategy of early antibody screening but also leads to the lack of companion diagnostic (CDx) criteria, which is critical to the objective response rate in early-stage clinical trials. Here, we show that galectin-8 (Gal-8) is a high-affinity functional ligand of LILRB4, and its ligation induces M-MDSC by activating STAT3 and inhibiting NF-κB. Significantly, Gal-8, but not APOE, can induce MDSC, and both ligands bind LILRB4 noncompetitively. Gal-8 expression promotes in vivo tumor growth in mice, and the knockout of LILRB4 attenuates tumor growth in this context. Antibodies capable of functionally blocking Gal-8 are able to suppress tumor growth in vivo. These results identify Gal-8 as an MDSC-driving ligand of LILRB4, and they redefine a class of antibodies for solid tumors.

Coupling effect of reaction conditions on the catalytic activity of Cu-Mn composite oxide catalysts for toluene.

Volatile organic compounds (VOCs) are one of the major components of air pollution. Catalytic combustion is a promising technology for the treatment of VOCs and at its center is the preparation of efficient and cheap catalysts. In this study, by loading copper (Cu) and manganese (Mn) on Santa Barbara Amorphous-15 (SBA-15) molecular sieve, the Cux-Mny/SBA-15 (x = 1, 2; y = 1, 2) composite metal oxide catalyst was prepared using the equal volume impregnation method. Their performance in the toluene catalytic combustion reaction was investigated by adjusting the molar ratio (x : y), and the loading of Cu and Mn. The results of the Brunner-Emmett-Teller (BET), X-ray diffraction (XRD), scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS) analyses show that the CuMnO spinel phase can be detected in the Cu-Mn composite metal oxide catalyst doped with a low concentration of Cu. The overall rod-like structure of the fibrous network structure provides a large specific surface area, and the particle crystallinity is low and the dispersion is good. Due to the synergistic effect of Cu and Mn, the greater the amount of Mn3+ and adsorbed oxygen species (Oads) that are available, and the higher the turnover frequency (TOF) value, the better and more superior catalytic performance and excellent stability is obtained, when compared with the single-component oxides used in toluene catalytic combustion. After a continuous catalytic reaction for 12 h, the toluene conversion rate remained above 95%. The coupling effect of the catalytic reaction temperature and concentration of oxygen on the catalytic combustion of toluene was also studied. At a low reaction temperature (<250 °C), the increase of the concentration of oxygen played a superior role in promoting the conversion of toluene. The kinetic analysis of the toluene catalytic combustion process showed that the catalytic combustion of toluene by Cu-Mn/SBA-15 followed both the Mars-Van Krevelen (MVK) and Langmuir-Hinshelwood (L-H) reaction mechanisms. With the increase of the Oads amount caused by the decrease of the Cu ratio, the proportion of the L-H reaction mechanism increases.

Co-pyrolysis of peanut shell with municipal sludge: reaction mechanism, product distribution, and synergy.

Biomass/sludge co-pyrolysis contributes to the high-efficiency resource utilization, harmless treatment, and reduction in volume of sludge. Due to the complexity of co-pyrolysis reaction, it is essential to evaluate the thermodynamic behavior, synergy, and reaction mechanism of this process to make it commercially viable. In this work, the pyrolysis properties, thermodynamic analysis and product distribution of municipal sludge (MS), peanut shell (PS), and their blends with various sludge mass ratios (SMRs) were investigated by a thermogravimetric analyzer and a fixed bed reactor. There was a considerable synergy existing in the process of PS/MS co-pyrolysis, and the synergy occurred mainly at the devolatilization phase, accelerating the mixture pyrolysis. When the conversion rate α was less than 0.7, the apparent activation energy decreased continuously with SMR at the same α; however, it increased dramatically with SMR when α was greater than 0.7. Reactants and reaction stages greatly affected the kinetic mechanism of fuel pyrolysis, and this finding was beneficial for the numerical simulation of mixture pyrolysis. Based on the conclusions and precision of this work, the mass ratio of PS to MS was recommended to be 6:4, which had the strongest synergy, with a gas yield of 26.69 wt.% at 600°C and a lower heating value (LHV) of pyrolysis gas of 14.89 MJ/Nm3.

G-MDSC-derived exosomes mediate the differentiation of M-MDSC into M2 macrophages promoting colitis-to-cancer transition.

BACKGROUNDS: In inflammatory bowel disease microenvironment, transdifferentiation of myeloid-derived suppressor cells (MDSCs) and M2 macrophage accumulation are crucial for the transition of colitis-to-cancer. New insights into the cross-talk and the underling mechanism between MDSCs and M2 macrophage during colitis-to-cancer transition are opening new avenues for colitis-associated cancer (CAC) prevention and treatment. METHODS: The role and underlying mechanism that granulocytic MDSCs (G-MDSCs) or exosomes (Exo) regulates the differentiation of monocytic MDSCs (M-MDSCs) into M2 macrophages were investigated using immunofluorescence, FACS, IB analysis, etc, and employing siRNA and antibodies. In vivo efficacy and mechanistic studies were conducted with dextran sulfate sodium-induced CAC mice, employed IL-6 Abs and STAT3 inhibitor. RESULTS: G-MDSCs promote the differentiation of M-MDSC into M2 macrophages through exosomal miR-93-5 p which downregulating STAT3 activity in M-MDSC. IL-6 is responsible for miR-93-5 p enrichment in G-MDSC exosomes (GM-Exo). Mechanistically, chronic inflammation-driven IL-6 promote the synthesis of miR-93-5 p in G-MDSC via IL-6R/JAK/STAT3 pathway. Early use of IL-6 Abs enhances the effect of STAT3 inhibitor against CAC. CONCLUSIONS: IL-6-driven secretion of G-MDSC exosomal miR-93-5 p promotes the differentiation of M-MDSC into M2 macrophages and involves a STAT3 signaling mechanism that promote colitis-to-cancer transition. Combining STAT3 inhibitors with strategies that inhibit IL-6-mediated G-MDSC exosomal miR-93-5 p production is beneficial for the prevention and treatment of CAC.

Optimum fractionation of radiation to combine PD-1 blockade.

The optimum fractionation of radiation to combine with immune checkpoint blockade is controversial. This study aimed to investigate the fractionated radiation to maximize immunity during combination therapy. To evaluate the abscopal effect, C57BL/6 hPD-1 knock-in mice bearing two syngeneic contralateral MC38 murine colon cancer tumors were treated with four distinct regimens of radiotherapy. Three fractions of 8 Gy were chosen as the optimal fractionation to combine with anti-PD-1 as the optimal fractionation for maximizing immunity. Anti-PD-1 administration enhanced both local and systemic antitumor immunity in a cytotoxic T cell-dependent manner. Meanwhile, the spleen exhibited decreased myeloid-derived suppressor cells (MDSCs) under combination treatment. Furthermore, RNA-sequencing revealed significantly increased tumor necrosis factor (TNF) receptors and cytokines associated with lymphocyte infiltration in the combining group. Here we demonstrate that the hypofractionation of 8 Gy × 3f was the optimum-fractionated dosage to maximize immunity, and the combination of anti-PD-1 showed promising results in boosting abscopal effect. Underlying mechanisms may include the activation of T cells and the reduction of MDSCs, which is achieved through the action of TNF and related cytokines. This study indicates a radioimmunotherapy dosage painting method that can be developed to overcome present limitations in tumor immunosuppression.

Research on the optimum carbonization process of walnut shell based on dynamic analysis.

Walnut shell is characterized by high yield, high fixed carbon content, and low ash content. In this paper, the thermodynamic parameters for walnut shell during the carbonization process is investigated, and its carbonization and mechanism are discussed. Then, the optimal carbonization process of walnut shell is proposed. Results demonstrated that the comprehensive characteristic index of pyrolysis first increases and then decreases with the increase of heating rate and reaches the peak at about 10 °C min-1. Note that the carbonization reaction intensifies at this heating rate. The carbonization process of walnut shell is a complex reaction involving multiple steps. It decomposes hemicellulose, cellulose, and lignin in stages, and the activation energy of this process gradually increases. The simulation and experimental analyses showed that the optimal process presents a heating time of 14.8 min, final temperature of 324.7 °C, holding time of 55.5 min, particle size of material of about 2 mm, and optimum carbonization rate of 69.4%.

In Silico Studies of the Impact of Rotational Errors on Translation Shifts and Dose Distribution in Image-Guided Radiotherapy.

Objective: To compare the 6-dimensional errors of different immobilization devices and body regions based on 3-dimensional cone beam computed tomography for image-guided radiotherapy and to further quantitatively evaluate the impact of rotational corrections on translational shifts and dose distribution based on anthropomorphic phantoms. Materials and Methods: Two hundred ninety patients with cone beam computed tomographies from 3835 fractions were retrospectively analyzed for brain, head & neck, chest, abdomen, pelvis, and breast cases. A phantom experiment was conducted to investigate the impact of rotational errors on translational shifts using cone beam computed tomography and the registration system. For the dosimetry study, pitch rotations were simulated by adjusting the breast bracket by ±2.5°. Roll and yaw rotations were simulated by rotating the gantry and couch in the planning system by ±3.0°, respectively. The original plan for the breast region was designed in the computed tomography image space without rotation. With the same planning parameters, the original plan was transplanted into the image space with different rotations for dose recalculation. The effect of these errors on the breast target and organs at risk was assessed by dose-volume histograms. Results: Most of the mean rotational errors in the breast region were >1°. A single uncorrected yaw of 3° caused a change of 2.9 mm in longitudinal translation. A phantom study for the breast region demonstrated that when the pitch rotations were -2.5° and 2.5° and roll and yaw were both 3°, the reductions in the planning target volumes-V50 Gy were 20.07% and 29.58% of the original values, respectively. When the pitch rotation was +2.5°, the left lung V5 Gy and heart Dmean were 7.49% and 165.76 Gy larger, respectively, than the original values. Conclusions: Uncorrected rotations may cause changes in the values and directions of translational shifts. Rotational corrections may improve the patient setup and dose distribution accuracy.

Construction of SNP fingerprint and population genetic analysis of honeysuckle germplasm resources in China.

Introduction: The flower buds of Lonicera japonica Thunb. are widely used in Chinese medicine for their anti-inflammatory properties, and they have played an important role in the fight against SARS COVID-19 and other major epidemics. However, due to the lack of scientific and accurate variety identification methods and national unified standards, scattered and non-standardized management in flower bud production has led to mixed varieties that have caused significant difficulties in the cataloging and preservation of germplasm resources and the identification, promotion, and application of new L. japonica varieties. Methods: In this study, we evaluated the population structure, genetic relationships, and genetic fingerprints of 39 germplasm resources of Lonicera in China using simplified genome sequencing technology. Results: A total of 13,143,268 single nucleotide polymorphisms (SNPs) were identified. Thirty-nine samples of Lonicera were divided into four subgroups, and the population structure and genetic relationships among existing Lonicera germplasm resources were determined using principal component analysis, population structure analysis, and phylogenetic tree analysis. Through several stringent selection criteria, 15 additional streamlined, high-quality DNA fingerprints were filtered out of the validated 50 SNP loci and verified as being able to effectively identify the 39 Lonicera varieties. Discussion: To our knowledge, this is the first comprehensive study measuring the diversity and population structure of a large collection of Lonicera varieties in China. These results have greatly broadened our understanding of the diversity, phylogeny, and population structure of Lonicera. The results may enhance the future analysis of genetic diversity, species identification, property rights disputes, and molecular breeding by providing a scientific basis and reference data for these efforts.

LINC01004-SPI1 axis-activated SIGLEC9 in tumor-associated macrophages induces radioresistance and the formation of immunosuppressive tumor microenvironment in esophageal squamous cell carcinoma.

Radioresistance and immunosuppression remain the major obstacles in the anti-cancer treatments. This work studies the functions of sialic acid binding Ig like lectin 9 (SIGLEC9) and its related molecules in radioresistance and immunosuppression in esophageal squamous cell carcinoma (ESCC). The single-cell analysis showed that SIGLEC9 was mainly expressed on tumor-associated macrophages (TAMs). Monocytes-derived macrophages were co-cultured with ESCC cells and subjected to radiotherapy. High or low doses of radiotherapy induced SIGLEC9 upregulation and M2 polarization of TAMs. Artificial inhibition of SIGLEC9 in TAMs suppressed the radioresistance and immunosuppressive tumor microenvironment (TME) in the co-cultured ESCC cells. Upstream molecules of SIGLEC9 were predicted via bioinformatics. LINC01004 recruited Spi-1 proto-oncogene (SPI1) in nucleus of TAMs to induce transcriptional activation of SIGLEC9. SIGLEC9 interacted with mucin 1 (MUC1). MUC1 overexpression in ESCCs induced M2 skewing of TAMs, enhanced radioresistance and immunosuppression, and promoted nuclear translocation of ß-catenin to suppress radiotherapy-induced ferroptosis of ESCC cells. These effects were blocked upon SIGLEC9 suppression. In vitro results were reproduced in the animal models with xenograft tumors. Taken together, this study demonstrates that the LINC01004-SPI1 axis-activated SIGLEC9 in TAMs induces radioresistance and the formation of immunosuppressive TME in ESCC.

Co-combustion of high alkali coal with municipal sludge: Thermal behaviour, kinetic analysis, and micro characteristic.

Blending sludge rich in protein and aliphatic hydrocarbons into the high alkali coal (HAC) has been demonstrated to reduce the ash melting temperature of the HAC/sludge mixture, thereby increasing the effectiveness and efficiency of liquid slagging. However, whether the incorporation of sludge can affect the combustion stability of the original coal-fired boiler is still debatable. As the combustion stability of the fuel can directly affect the operational safety of the boiler, it is of great practical value for exploring the effect of sludge incorporation on the combustion performance of HAC. In this work, the thermal behaviour and microscopic properties of individual HAC, municipal sludge (MS) and HAC/MS mixtures were tested using a Thermogravimetric analyser (TGA) and a Fourier transform infrared (FTIR) spectrometer, respectively. The exothermic, thermodynamic and functional group evolution patterns during the combustion of these samples were also evaluated. Ignition temperatures (Ti) of the HAC/MS mixtures were relatively lower than that of individual HAC, and decreased with the increase in sludge mass ratio (SMR). The synergistic effect of the co-combustion of HAC and MS resulted in a slightly higher total heat release during the combustion of MS10HAC90 (i.e., the mass percentage of MS and HAC is 1:9) than HAC alone, however, the total heat release of the blend decreased progressively with increasing SMR. The experimental values of the average Eα for all four mixtures were lower than the theoretical values, indicating that the addition of MS lowered the reaction energy barriers of the mixtures. Consumption rates of the principal groups in samples during the oxidation and combustion all tended to increase progressively with increasing SMR. There are three major synergistic effects existing during co-combustion of HAC and MS: (1) the reaction of free radicals with benzene molecules; (2) the interaction of free radicals; and (3) the catalytic effect of alkali and alkaline earth metals. These findings can provide theoretical guidance for the determination of key parameters (mixing ratio) for the blending of HAC and MS, and can fill the research gap in terms of microscopic reactivity and synergistic effects during the co-combustion of HAC and MS.

Research on Thermal Behaviors and NO x Release Properties during Combustion of Sewage Sludge, Sawdust, and Their Blends.

To investigate the thermal behaviors and NO x emission properties during combustion of sewage sludge (SS), sawdust (SD), and their blends (SS5SD5, SS3SD7, and SS1SD9 with SD proportions of 50, 70, and 90 wt %, respectively), tests were conducted using thermogravimetry-mass spectrometry (TG-MS), Fourier transform infrared spectroscopy (FTIR), and a tube furnace in this study. Results indicated that hydrogen in the fuel was mainly released during volatile combustion, and carbon conversion proceeded during the whole combustion process. With the SD proportion increasing, samples exhibited better combustion characteristics. Compared to SD, SS emitted more NO x due to its higher nitrogen content but showed lower conversion ratios from fuel nitrogen to NO x , and the NO x yields decreased significantly with the increase in SD proportion. NO x emissions of higher volatile samples were more sensitive to temperature, and NO x yields of SD and SS1SD9 continued to decrease from 800 to 1000 °C, whereas NO x yields of SS, SS5SD5, and SS3SD7 changed slightly from 800 to 900 °C and decreased significantly from 900 to 1000 °C. Synergistic effects of cocombustion on NO x emission varied with the blending ratio and temperature. SS5SD5 and SS3SD7 always presented a positive NO x reduction performance, and SS1SD9 exhibited opposite NO x reduction effects at different temperatures. Synthetically considering the SS disposal capacity, combustion characteristic, and NO x yield, an SS proportion of around 30% in blends is more recommended in practical applications.

Amino-acid modulated hierarchical In/H-Beta zeolites for selective catalytic reduction of NO with CH4 in the presence of H2O and SO2.

Selective catalytic reduction of NO with CH4 (CH4-SCR) has been studied over a series of amino-acid mediated hierarchical beta zeolites with indium exchange. Amino acid mesoporogens greatly affect the NO reduction (DeNOx) efficiency of In/H-Beta catalysts. Mesoporous In/H-Beta-P synthesized using proline exhibits the highest NOx removal efficiency of 40% in excess oxygen and poisonous SO2 and H2O, 10% higher than our previously optimized In/H-Beta catalyst using commercial beta zeolites with a similar Si/Al ratio. Analyses using XRD, N2 adsorption-desorption, EPR, SEM, TEM, EDX, ICP, 27Al and 29Si MAS NMR, XPS, H2-TPR, NH3-TPD, and Py-IR reveal that amino acids promote beta crystallization, modulate zeolite acid sites and surface oxygen species, and generate hierarchical pore architectures without affecting the Si/Al ratio, indium content, and percentage of the active InO+ species. The mosaic-structured In/H-Beta-P exhibits the strongest Brønsted acidity and surface labile oxygen which enhance the oxyindium interaction with the zeolite framework, promoting CH4-SCR activity. The strong acidity, surface active oxygen species, and mesopores lead to excellent stability of the In/H-Beta-P catalyst in the presence of SO2 and H2O, withstanding several catalytic DeNOx cycles under harsh reaction conditions.

Correction: IL-17A weakens the antitumor immunity by inhibiting apoptosis of MDSCs in Lewis lung carcinoma bearing mice.

[This corrects the article DOI: 10.18632/oncotarget.13978.].

Research on Combustion Properties and Pollutant Emission Characteristics of Blends of Maltol Byproduct/Pine Sawdust.

In this paper, the combustion and pollutant emission characteristics of maltol byproduct, pine sawdust, and their blends were experimentally studied by thermogravimetry, tube furnace experiment, and scanning electron microscopy. The results show that the combustion process of maltol byproduct, pine sawdust, and their blends can be divided into three stages, in which the volatile release of the maltol byproduct includes two stages. The ignition temperature of the blended fuel is lower than that of sawdust. The NO x produced by combustion of the blended fuel is lower than that produced by sawdust combustion alone, and the SO2 emission is always at a low level. There is a certain synergy between maltol byproduct and pine sawdust mixed combustion. Comprehensively comparing the combustion characteristics and emission characteristics, the blended fuel made by adding less than 10% maltol byproduct into pine sawdust can improve the combustion characteristics and reduce emissions, and 10% is the best proportion of the blended fuel.

Comparative Analyses between Raw and Preoxidized Pulverized Coals: Combustion Behaviors and Thermokinetic and Microcharacteristics.

Investigating the difference in the combustion performance and microcharacteristics of oxidized and raw pulverized coal (PC) can contribute to effectively prevent and control the spontaneous combustion of deposited coal dust in high-temperature environment and further help guarantee the safe operation of coal-fired boiler. In this study, the combustion performance and thermokinetic and microcharacteristics of three raw coal samples and their preoxidized forms were explored by a thermogravimetric analyzer (TGA) and Fourier transform infrared spectroscopy (FTIR). According to the characteristic temperatures and variations of the mass loss rate during heating, the entire combustion process of PC was divided into four periods. For each type of coal, the preoxidized PC had relatively lower characteristic temperatures than the corresponding raw PC. The preoxidized samples had larger values of ignition index (C ig) and comprehensive combustibility index (S), but lower values of burnout index (C b) than raw samples. The values of apparent activation energy (E) for the preoxidized PC were below that of the corresponding raw PC at the same conversion rate (α), which suggested the preoxidized PC required relatively less energy to react and was more prone to spontaneous combustion. In addition, although parts of -OH, C=O, and aliphatic hydrocarbon groups were consumed after the preoxidation treatment, the increase in C-O and -COO- bonds compensated for the adverse effect of the reduction of the aforementioned groups on coal combustion.

Online MR evaluation of inter- and intra-fraction uterus motions and bladder volume changes during cervical cancer external beam radiotherapy.

PURPOSE/OBJECTIVE(S): The purpose of the study was to assess the uterus motions and bladder volume changes of fractional movements in cervical sites throughout the external beam radiotherapy (EBRT) treatment. MATERIALS/METHODS: A prospective online MR imaging tracking study was conducted in EBRT 43 patients with at least 4 scans during each treatment (before: ultrasound scan, MRI scan, CBCT scan, after: MRI scan) were included. In order to improve the treatment repeatability, each patient was instructed to empty the bladder and drink 500 ml water 1 h before CT simulation and each treatment. If the ultrasound scan result reached the CT simulation volume of bladder, the treatment began. Bladder was outlined on the T2 weighted axial sequence and CBCT image by the two observers to avoid the influence of contouring. The data of bladder volume and scanning time were accurately recorded. The bladder volumes, filling rates and uterus motion were retrospectively analyzed by MIM software. RESULTS: Inter-fraction variation of the bladder volume was significant (p < 0.0001). Intra-fraction mean increase of the bladder volume was modest (30 cc) but significant (p < 0.001). Both inter- and intra-fraction of the uterus motion were significant. The average time between the pre-and post-fraction MRI scans was 27.82 ± 7.12 min (range 10-55 min) for IMRT plans and 24.14 ± 5.86 min (range7-38 min) for VMAT plan. Average bladder filling rate was 3.43 ml/min. The bladder filling rate did not change significantly with the course of treatment, but the bladder was more intolerant. CONCLUSION: This is the most detailed assessment of intra-fraction and inter-fraction motion during EBRT for cervical cancer. Finally, this study will inform appropriate treatment margins for online adaptive radiotherapy. We suggest that at least one image scan is needed before the EBRT. The portable US scanner provides a quick but unreliable measurement of the bladder volume. There is a significant statistical difference between the results of ultrasonic scanning and that of image scanning.

THADA drives Golgi residency and upregulation of PD-L1 in cancer cells and provides promising target for immunotherapy.

BACKGROUND: The abnormal upregulation of programmed death-ligand 1 (PD-L1) in cancer cells inhibits T cell-mediated cytotoxicity, but the molecular mechanisms that drive and maintain PD-L1 expression are still incompletely understood. METHODS: Combined analyses of genomes and proteomics were applied to find potential regulators of PD-L1. In vitro experiments were performed to investigate the regulatory mechanism of PD-L1 by thyroid adenoma associated gene (THADA) using human colorectal cancer (CRC) cells. The prevalence of THADA was analyzed using CRC tissue microarrays by immunohistochemistry. T cell killing assay, programmed cell death 1 binding assay and MC38 transplanted tumor models in C57BL/6 mice were developed to investigate the antitumor effect of THADA. RESULTS: THADA is critically required for the Golgi residency of PD-L1, and this non-redundant, coat protein complex II (COPII)-associated mechanism maintains PD-L1 expression in tumor cells. THADA mediated the interaction between PD-L1 as a cargo protein with SEC24A, a module on the COPII trafficking vesicle. Silencing THADA caused absence and endoplasmic reticulum (ER) retention of PD-L1 but not major histocompatibility complex-I, inducing PD-L1 clearance through ER-associated degradation. Targeting THADA substantially enhanced T cell-mediated cytotoxicity, and increased CD8+ T cells infiltration in mouse tumor tissues. Analysis on clinical tissue samples supported a potential role of THADA in upregulating PD-L1 expression in cancer. CONCLUSIONS: Our data reveal a crucial cellular process for PD-L1 maturation and maintenance in tumor cells, and highlight THADA as a promising target for overcoming PD-L1-dependent immune evasion.

Out-of-field dose assessment for a 1.5 T MR-Linac with optically stimulated luminescence dosimeters.

PURPOSE: To assess the out-of-field surface and internal dose of the 1.5 T MR-Linac compared to the conventional external beam linac using optically stimulated luminescence dosimeters (OSLDs), and evaluate the out-of-field dose calculation accuracy of the Monaco treatment planning system (TPS) of the 1.5T MR-Linac. METHODS: A cubic solid water phantom, with OSLDs on the surface, was vertically irradiated by MR-Linac square fields with different sizes. In addition, OSLDs were arranged out of the beam edges in four directions. An anthropomorphic adult phantom, with 125 cm3 simulated volume, was irradiated in four orthogonal directions by both MR-Linac and conventional linac at the head, thoracic, and pelvic sites. Out-of-field doses were measured by OSLDs on both the surface and internal emulational organs at risk (OARs). The results were compared to the simulated dose from Monaco TPS. RESULTS: At different field sizes (5 × 5 to 20 × 20 cm2 ) and distances (1 to 10 cm) to beam edge, the out-of-field surface dose measured on MR-Linac varied from 0.16 % (10 cm to 5 × 5 cm2 edge) to 7.02 % (1 cm to 20 × 20 cm2 edge) of the maximum dose laterally and from 0.14 % (10 cm to 5 × 5 cm2 edge) to 8.56 % (1 cm to 20 × 20 cm2 edge) of the maximum dose longitudinally. Compared to the OSLDs measured data, the Monaco TPS presented an overestimate of the out-of-field dose of OARs at 0-2 % isodose area on both surface and internal check points, and the overestimation gets greater as the distance increases. The underestimation was found to be 0-35% at 2-5% isodose area on both surface and internal check points. Compared to the conventional linac, MR-Linac delivered higher average values of out-of-field dose on surface check points (20%, 19%, 21%) and internal simulated OARs (42%, 37%, 9%) of the anthropomorphic phantom at head, thoracic, and pelvic irradiations, respectively. CONCLUSIONS: Compared to the conventional linac, MR-Linac has the same out-of-field dose distribution. However, considering the absolute dose values, MR-Linac delivered relatively higher out-of-field doses on both surface and internal OARs. Additional radiation shielding to patients undergoing MR-Linac may provide protection from out-of-field exposure.