Investigation of the Interaction Between Lactones and Ketones in a Cheddar Cheese Matrix Using Feller's Additive Model, σ-τ Plots, U-Models, and Aroma Addition Experiments.

The objective of this study was to examine the sensory interactions between lactones and ketones in a cheddar simulation matrix through perceptual interaction analysis. The olfactory thresholds of 6 key lactones had values ranging from 8.32 to 58.88 µg/kg, whereas those of the 4 key ketones ranged from 6.61 to 660.69 µg/kg. Both Feller's additive model and σ-τ plots demonstrated complex interactions in 24 binary mixtures composed of the 6 lactones and 4 ketones, including synergy, addition, and masking effects. Specifically, we found that 6 binary mixtures exhibited aroma synergistic effects using both methods. Moreover, the σ-τ plot showed a synergistic effect of aroma in 3 ternary mixtures. The U-model further confirmed the synergistic effects of the 6 groups of binary systems and 3 groups of ternary systems on aroma at actual cheese concentrations. In an aroma addition experiment, the combination of δ-octalactone and diacetyl in binary mixtures had the most pronounced impact on enhancing milk flavor. In ternary mixtures, 2 combinations, namely δ-octalactone/δ-dodecalactone/diacetyl and γ-dodecalactone/δ-dodecalactone/acetoin, significantly enhanced the milky and sweet aroma properties of cheese, while also enhancing the overall acceptability of the cheese aroma.

Grad-MobileNet: A Gradient-Based Unsupervised Learning Method for Laser Welding Surface Defect Classification.

Deep learning technology has advanced rapidly and has started to be applied for the detection of welding defects. In the manufacturing process of power batteries for new energy vehicles, welding defects may occur due to the high directivity, convergence, and penetration of the laser beam. The accuracy of deep learning prediction relies heavily on big data, but balanced big data of welding defects is hard to acquire at the battery production site. In this paper, the authors construct a dataset named RIAM, which consists of images captured from an industrial environment for laser welding of power battery modules. RIAM contains four types of images: Normality, Lack of fusion, Surface porosity, and Scaled surface. The characteristics of RIAM are carefully considered in the application scenarios. Moreover, this paper proposes a gradient-based unsupervised model named Grad-MobileNet, which can be trained with only a few normal images and can extract the feature gradients of the input images. Welding defects can then be classified by the gradient distribution. This model is based on MobileNetV3, which is a lightweight convolutional neural network (CNN), and achieves 99% accuracy, which is higher than the accuracy expected from supervised learning.

Comparison of UV-based advanced oxidation processes for the removal of different fractions of NOM from drinking water.

This study examined the effectiveness for degradation of hydrophobic (HPO), transphilic (TPI) and hydrophilic (HPI) fractions of natural organic matter (NOM) during UV/H2O2, UV/TiO2 and UV/K2S2O8 (UV/PS) advanced oxidation processes (AOPs). The changing characteristics of NOM were evaluated by dissolved organic carbon (DOC), the specific UV absorbance (SUVA), trihalomethanes formation potential (THMFP), organic halogen adsorbable on activated carbon formation potential (AOXFP) and parallel factor analysis of excitation-emission matrices (PARAFAC-EEMs). In the three UV-based AOPs, HPI fraction with low molecular weight and aromaticity was more likely to degradate than HPO and TPI, and the removal efficiency of SUVA for HPO was much higher than TPI and HPI fraction. In terms of the specific THMFP of HPO, TPI and HPI, a reduction was achieved in the UV/H2O2 process, and the higest removal rate even reached to 83%. UV/TiO2 and UV/PS processes can only decrease the specific THMFP of HPI. The specific AOXFP of HPO, TPI and HPI fractions were all able to be degraded by the three UV-based AOPs, and HPO content is more susceptible to decompose than TPI and HPI content. UV/H2O2 was found to be the most effective treatment for the removal of THMFP and AOXFP under given conditions. C1 (microbial or marine derived humic-like substances), C2 (terrestrially derived humic-like substances) and C3 (tryptophan-like proteins) fluorescent components of HPO fraction were fairly labile across the UV-based AOPs treatment. C3 of each fraction of NOM was the most resistant to degrade upon the UV-based AOPs. Results from this study may provide the prediction about the consequence of UV-based AOPs for the degradation of different fractions of NOM with varied characteristics.

Experimental and theoretical investigation on degradation of dimethyl trisulfide by ultraviolet/peroxymonosulfate: Reaction mechanism and influencing factors.

With a large amount of domestic sewage and industrial wastewater discharged into the water bodies, sulfur-containing organic matter in wastewater produced volatile organic sulfide, such as dimethyl trisulfide (DMTS) through microorganisms, caused the potential danger of drinking water safety and human health. At present, there is still a lack of technology on the removal of DMTS. In this study, the ultraviolet/peroxymonosulfate (UV/PMS) advanced oxidation processes was used to explore the degradation of DMTS. More than 90% of DMTS (30 µg/L) was removed under the conditions of the concentration ratio of DMTS to PMS was 3:40, the temperature (T) was 25 ± 2℃, and 10 min of irradiation by a 200 W mercury lamp (365 nm). The kinetics rate constant k of DMTS reacting with hydroxyl radical (HO·) was determined to be 0.2477 min-1. Mn2+, Cu2+ and NO3- promoted the degradation of DMTS, whereas humic acid and Cl- in high concentrations inhibited the degradation process. Gas chromatography-mass spectrometry was used to analyze the degradation products and the degradation intermediates were dimethyl disulfide and methanethiol. Density functional theory was used to predict the possible degradation mechanism according to the frontier orbital theory and the bond breaking mechanism of organic compounds. The results showed that the SS, CS and CH bonds in DMTS molecular structure were prone to fracture in the presence of free radicals, resulting in the formation of alkyl radicals and sulfur-containing radicals, which randomly combined to generate a variety of degradation products.

Renal puncture access using a blunt needle: proposal of the blunt puncture concept.

PURPOSE: Severe haemorrhage in percutaneous nephrolithotomy (PCNL) is an alarming event, and preventing injury to renal major vessels is a challenge. We evaluated the efficiency of a blunt needle in renal puncture procedures. METHODS: We first retrospectively reviewed the embolization images of post-PCNL patients to analyse the types of arteries injured, which were considered target arteries. Then, either a blunt needle or a conventional needle was used to directly puncture target arteries in ex vivo porcine kidneys and to establish renal access ex vivo and in vivo. The primary outcome was the incidence of target artery injuries, which were observed by digital subtraction angiography, nephroscopy and 3-dimensional endocasts. The secondary outcome was the rate of excreted fluid per access. RESULTS: The segmental and interlobar arteries were the most common types of injured arteries that needed to be embolized after PCNL. When these arteries were punctured directly, blunt needles reduced injury (1/20 vs. 16/20; OR 4.750; 95% CI 1.966-11.478; P < .001) by 76% compared to injuries induced by conventional needles. Moreover, the blunt needle group also had a significantly lower incidence of these arteries' injuries ex vivo due to renal puncture and yielded a lower rate of excreted fluid in ex vivo and in vivo renal puncture procedures. CONCLUSION: A blunt needle for renal puncture can be effective in reducing injury to renal major arteries and the accompanying haemorrhage. We propose the concept of blunt puncture, which may be a promising method for achieving safe renal access in PCNL.

Thoracic Paravertebral Block Ameliorates Postoperative Delirium in Geriatric Patients.

OBJECTIVES: Thoracic surgery often causes postoperative delirium (POD) in geriatric patients. This study aimed to explore the effect of ultrasound-guided continuous thoracic paravertebral block (UG-TPVB) on POD in geriatric patients undergoing pulmonary resection. METHODS: Total 128 patients who underwent pulmonary resection were randomly allocated to either the conventional patient-controlled analgesia (PCA) group or the UG-TPVB group (n = 64 per group). The consumption of opioid agents (propofol and remifentanil), postoperative hospital stay, postoperative pulmonary atelectasis, postoperative nausea/vomiting, and postoperative itchiness were recorded. The diagnosis of delirium was dependent on the Nursing Delirium Screening Scale. The postoperative pain was assessed by visual analogue scale (VAS) score. The serum levels of interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α were used to evaluate the postoperative neuroinflammation. RESULTS: The consumption of propofol and remifentanil, postoperative hospital stay, postoperative pulmonary atelectasis, postoperative nausea/vomiting, and postoperative itchiness in the UG-TPVB group were lower than that in the PCA group. Compared with the PCA group, the prevalence of POD was decreased in the UG-TPVB group. In addition, use of UG-TPVB not only reduced postoperative pain (VAS score) but also decreased postoperative neuroinflammation compared with PCA in geriatric patients undergoing pulmonary resection. CONCLUSIONS: This study determined the benefits of UG-TPVB over PCA, providing an effectiveness approach to alleviate POD in geriatric patients undergoing pulmonary resection.

An Ultrasonic Laminated Transducer for Viscoelastic Media Detection.

Based on the principle of underwater transducers, an ultrasonic four-laminated transducer with a frequency of 1 MHz was proposed to solve the problem of large energy attenuation when ultrasonic waves propagate in viscoelastic media. First, this study targeted solid rocket propellant as the research object, and the energy attenuation characteristics of ultrasonic waves propagating in viscoelastic media were analyzed through the derivation of the wave equation. Second, the structure of a four-laminated transducer with a frequency of 1 MHz was designed, and the resonance frequency was obtained by a graphical method. The sound field simulation and experimental results showed that the gain of the four-laminated transducer was 15 dB higher than that of the single-wafer transducer. An ultrasonic feature scanning system was built to complete the qualitative and quantitative detection of the smallest artificial hole (ϕ2 mm × 10 mm). Finally, two different natural defects were scanned, and the results were compared with those obtained using an industrial computed tomography detection system. The results showed that the ultrasonic method was more accurate in characterizing two natural defects. The primary cause was that the industrial CT was not sensitive to defects parallel to the incident direction of the ray. Therefore, this study not only achieved the qualitative and quantitative nondestructive testing of solid rocket propellants, but also provides an important reference for other viscoelastic components.

Disinfection characteristics of Pseudomonas peli, a chlorine-resistant bacterium isolated from a water supply network.

Lack of microbial contamination is crucial for drinking water quality and safety. Chlorine-resistant bacteria in drinking water distribution systems pose a threat to drinking water quality. A bacterium was isolated from an urban water supply network in northern China and identified as Pseudomonas peli by 16S rDNA gene analysis. This P. peli strain had high chlorine tolerance. The CT value (the product of disinfectant concentration and contact time) to achieve 3 lg unit (i.e. 99.9%)-inactivation of this P. peli isolate was 51.26-90.36 mg min/L, inversely proportional to the free chlorine concentration. Chlorine dioxide could inactivate the bacterium faster and more efficiently than free chlorine, as shown by flow cytometry. Thiazole orange plus propidium iodide staining indicated that free chlorine and chlorine dioxide inactivated P. peli primarily by disrupting the integrity and permeability of the cell membrane. The P. peli was also sensitive to ultraviolet (UV) radiation; a UV dose of 40 mJ/cm2 achieved 4 lg unit (99.99%)-inactivation. The Hom model was more suitable for analyzing the disinfection kinetics of P. peli than the Chick and Chick-Watson models.

Identification and inactivation of Gordonia, a new chlorine-resistant bacterium isolated from a drinking water distribution system.

Chlorine-resistant bacteria threaten drinking water safety in water distribution systems. In this study, a novel chlorine-resistant bacterium identified as Gordonia was isolated from the drinking water supply system of Jinan City for the first time. We examined the resistance and inactivation of the isolate by investigating cell survival, changes in cell morphology, and the permeability of cell membranes exposed to chlorine. After 240 min chlorine exposure, the chlorine residual was greater than 0.5 mg L-1 and the final inactivation was about 3 log reduction, which showed that the Gordonia strain had high chlorine tolerance. Flow-cytometric analysis indicated that, following sodium hypochlorite treatments with increasing membrane permeability, culturable cells enter a viable but nonculturable state and then die. We also investigated the inactivation kinetics of Gordonia following chlorine dioxide and ultraviolet radiation treatment. We found that these treatments can effectively inactivate Gordonia, which suggests that they may be used for the regulation of chlorine-resistant microorganisms.

Ultraviolet-mediated peroxymonosulfate diminution of earthy and musty compound trichloroanisole in water.

Taste and odor (T&O) problem in water is one of the main obstacles to improve the quality of drinking water, and efficient water treatment processes are urgently needed to control T&O compounds. Ultraviolet-mediated peroxymonosulfate (UV/PMS) diminution of trichloroanisole (TCA) in water was investigated in this paper. The treatment of 2,3,6-trichloroanisole (2,3,6-TCA) by three advanced oxidation processes (UV, UV/H2O2 and UV/PMS) was compared, and UV/PMS stood out. SO4•- and HO• were produced in the UV/PMS, and their specific contributions to 2,3,6-TCA oxidation were investigated. The competitive kinetic model was applied to determine the second-order reaction rate between 2,3,6-TCA and SO4•- or HO•. The products of 2,3,6-TCA generated in UV/PMS were analyzed with gas chromatography/high resolution-mass spectrometry (GC/HR-MS), and the degradation mechanism was proposed. The effects of water matrices (chloride, bicarbonate and humic acid) on UV/PMS performance were studied, and the decontamination of 2,3,6-TCA in real water was carried out. The disinfection byproducts (DBPs) alteration from 2,3,6-TCA by UV/PMS - chlorination treatment was explored. Overall, UV/PMS can effectively deal with the T&O pollution of TCA in water.

Development of an inoculation technique for rapidly evaluating maize inbred lines for resistance to stalk rot caused by Fusarium spp. in the field.

Maize (Zea mays L.) stalk rot, caused primarily by the soil-borne fungal pathogen Fusarium spp., reduces maize quality and yield worldwide. This study was undertaken to develop and utilize a rapid continuous injection inoculation technique to evaluate maize inbred lines for resistance to Fusarium spp. under field conditions, which could facilitate the identification and development of new sources of host resistance to manage the disease. Continuous injection inoculation is a rapid, stable, and simple method that can evaluate the resistance of maize inbred lines to Fusarium stalk rot (FSR) within 20 days. To verify the feasibility and reliability of inoculation method, Fusarium graminearum, F. proliferatum, and F. subglutinans were isolated, identified, and inoculated into maize at the six-leaf stage (V6) by a veterinary adjustable bottle continuous vaccination syringe. Our results showed that out of a total of 97 inbred maize lines, six (6.2%) showed high resistance to maize stalk rot, 20 showed resistance (20.6%), 32 were susceptible (33.0%), and 39 were very susceptible (40.2%). Based on simple sequence repeat (SSR) markers, an analysis of molecular variance indicated a significant correlation between population of the inbred maize line and resistance to FSR (P = 0.001). Overall, this study provided a systematic, rapid, stable, and simple identification method for maize inbred lines resistant to FSR in the field. At the same time, this method was also suitable for genetic diversity analysis of maize inbred lines resistant to FSR.

Effects of Sulfamethoxazole Exposure on the Growth, Antioxidant System of Chlorella vulgaris and Microcystis aeruginosa.

Sulfamethoxazole (SMZ) is a kind of sulfonamides antibiotic, which is widely used in human life. This study investigated the effects of SMZ on physiological and biochemical indexes of Chlorella vulgaris (C. vulgaris) and Microcystis aeruginosa (M. aeruginosa) for 35-day. The results showed that SMZ inhibited the growth and Chl-a content of C. vulgaris and M. aeruginosa, and growth inhibition rate was 8.06%-95.86%, Chl-a content decreased 2.44%-98.04%. SMZ resulting in increased SOD and CAT activity and destroyed the dynamic balance of antioxidant system. In addition, SMZ increased the content of malondialdehyde (MDA) in algae, destroyed the cell membrane to a certain extent, which was 1.8-7.3 folds higher than the control group. High concentration of SMZ can make algae cells exceed the limit of cell antioxidant capacity. Coupled with the serious damage of cell membrane, algae cells begin to appear a large number of death phenomenon.

Exogenous 2-(3,4-Dichlorophenoxy) triethylamine ameliorates the soil drought effect on nitrogen metabolism in maize during the pre-female inflorescence emergence stage.

BACKGROUND: Nitrogen (N) metabolism plays an important role in plant drought tolerance. 2-(3,4-Dichlorophenoxy) triethylamine (DCPTA) regulates many aspects of plant development; however, the effects of DCPTA on soil drought tolerance are poorly understood, and the possible role of DCPTA on nitrogen metabolism has not yet been explored. RESULTS: In the present study, the effects of DCPTA on N metabolism in maize (Zea mays L.) under soil drought and rewatering conditions during the pre-female inflorescence emergence stage were investigated in 2016 and 2017. The results demonstrated that the foliar application of DCPTA (25 mg/L) significantly alleviated drought-induced decreases in maize yield, shoot and root relative growth rate (RGR), leaf relative water content (RWC), net photosynthetic rate (Pn), stomatal conductance (Gs) and transpiration rate (Tr), and nitrate (NO3-), nitrite (NO2-), soluble protein contents, and nitrate reductase (NR), nitrite reductase (NiR), isocitrate dehydrogenase (ICDH), alanine aminotransferase (AlaAT) and aspartate aminotransferase (AspAT) activities. In addition, the foliar application of DCPTA suppressed the increases of intercellular CO2 concentration (Ci), ammonium (NH4+) and free amino acid contents, and the glutamate dehydrogenase (GDH) and protease activities of the maize. Simultaneously, under drought conditions, the DCPTA application improved the spatial and temporal distribution of roots, increased the root hydraulic conductivity (Lp), flow rate of root-bleeding sap and NO3- delivery rates of the maize. Moreover, the DCPTA application protected the chloroplast structure from drought injury. CONCLUSIONS: The data show, exogenous DCPTA mitigates the repressive effects of drought on N metabolism by maintained a stabilized supply of 2-oxoglutarate (2-OG) and reducing equivalents provided by photosynthesis via favorable leaf water status and chloroplast structure, and NO3- uptake and long-distance transportation from the roots to the leaves via the production of excess roots, as a result, DCPTA application enhances drought tolerance during the pre-female inflorescence emergence stage of maize.

Structural and functional abnormalities of vision-related brain regions in cirrhotic patients: a MRI study.

PURPOSE: Previous studies have focused on global cerebral alterations observed in cirrhosis. However, little was known about the specific abnormalities of vision-related brain regions in cirrhotic patients. In this study, we sought to explore neurological alterations of vision-related regions by measuring brain resting-state network connectivity, based on the structural investigation in cirrhotic patients without clinical sign of hepatic encephalopathy (HE). METHODS: Structural and functional magnetic resonance image (MRI) data were collected from 20 hepatitis B virus (HBV)-related cirrhotic patients without clinical sign of HE and from 20 healthy controls (HC). Voxel-based morphometric (VBM) analysis and brain functional network analysis were performed to detect abnormalities in cerebral structure and function. RESULTS: Cirrhotic patients showed regions with the most significant gray matter reduction primarily in vision-related brain regions, including the bilateral lingual gyri, left putamen, right fusiform gyrus, and right calcarine gyrus, and other significant gray matter reductions were distributed in bilateral hippocampus. Based on structural investigation focused on vision-related regions, brain functional network analysis revealed decreased functional connectivity between brain functional networks within vision-related regions (primary visual network (PVN), higher visual network (HVN), visuospatial network (VSN)) in the patient group compared with HC group. CONCLUSION: These results indicate that structural and functional impairment were evident in the vision-related brain regions in cirrhotic patients without clinical sign of hepatic encephalopathy. The physiopathology and clinical relevance of these changes could not be ascertained from the present study, which provided a basis for further evolution of the disease.

Distributed asynchronous measurement system fusion estimation based on inverse covariance intersection algorithm.

For state estimation of multi-source asynchronous measurement systems with measurement missing phenomena, this paper proposes a distributed sequential inverse covariance intersection (DSICI) fusion algorithm based on conditional Kalman filtering method. It is mainly divided into synchronized state space module, local filtering module and fusion estimation module. The missing measurements occurring in the system are modelled and described by a set of random variables obeying a Bernoulli distribution. The synchronized state space module uses a state iteration method to synchronize the asynchronous measurement system at the moment of measurement update and it ensures the integrity of the measurement information. The local filtering module uses a conditional Kalman filtering algorithm for filter estimation. The reliability of the local filtering results is guaranteed because the local estimator designs a method to interact information with the domain sensors. The fusion estimation module designs a DSICI fusion algorithm with higher accuracy and satisfying consistency, which fuses the filtering results provided by each sensor when the relevant information between multiple sensors is unknown. Simulation examples demonstrate the excellent performance of the proposed algorithm, with a 33% improvement in accuracy over existing algorithms and an iteration time of less than 3 ms.

Effect of UV/peroxymonosulfate pretreatment on disinfection byproduct (DBP) formation during post-chlorination of humic acid.

UV/peroxymonosulfate (UV/PMS) is a promising advanced oxidation technology in water treatment. This study aimed to investigate the impact of UV/PMS on humic acid (HA) and the influence of PMS dosage, pretreatment time, pH pretreatment, nitrate, nitrite, ammonium, and bicarbonate influencing factors on disinfection byproduct (DBP) formation during post-chlorination. With increased PMS dosage or pretreatment time, the UV/PMS treatment significantly reduced ultraviolet absorbance and increased mineralization. It altered the fractional constituent as humic substances were gradually transformed into building blocks and low-molecular-weight acids. However, most DBP formation increased initially and then decreased after subsequent chlorination. Rising nitrate or nitrite concentrations markedly promoted halonitromethane (HNM) formation. The presence of ammonia had a more significant impact on dichloroacetonitrile (DCAN) formation. Bicarbonate in UV/PMS pretreatment increased carbonated disinfection byproduct (C-DBP) formation, whereas it had a negligible impact on nitrogenous disinfection byproduct (N-DBP) formation. The present study revealed the impact of a series of influencing factors on DBP formation in UV/PMS reaction systems, providing comprehensive insights on applying UV/PMS in actual practice.

Tracking the impact of perfluoroalkyl acid emissions on antibiotic resistance gene profiles in receiving water by metagenomic analysis.

The ecological risks posed by perfluoroalkyl acids (PFAAs) to the aquatic environment have recently been of great concern. However, little information was available on the impact of PFAAs on antibiotic resistance genes (ARGs) profiles. In this study, the receiving river of the largest fluoropolymer production facility in China was selected to investigate the effects of PFAAs on ARGs profiles. The highest PFAAs concentration for water samples near the industrial effluent discharge point was 310.9 µg/L, which was thousands times of higher than the average concentration collected at upstream sites. Perfluorooctanoic acid accounted for more than 67.2 % of ∑PFAAs concentration in water samples collected at the downstream sites, followed by perfluorohexanoic acid (3.6 %-15.9 %). 145 ARG subtypes including high-risk ARGs were detected by metagenomic technology. The results indicated that the discharge of PFAA-containing effluents had a significant impact on the abundance and diversity of ARGs in receiving waters, and PFAAs and water quality parameters (e.g., pH, NH3N, CODMn, TP) could largely affect ARG profiles. Specifically, short-chain PFAAs had similar impacts on ARG profiles compared to the restricted long-chain PFAAs. This study confirmed the potential effects of PFAAs on ARGs in aquatic environment and provided more insights into the ecological risk raised by PFAAs.

Characterization of gene regulatory networks underlying key properties in human hematopoietic stem cell ontogeny.

Human hematopoiesis starts at early yolk sac and undergoes site- and stage-specific changes over development. The intrinsic mechanism underlying property changes in hematopoiesis ontogeny remains poorly understood. Here, we analyzed single-cell transcriptome of human primary hematopoietic stem/progenitor cells (HSPCs) at different developmental stages, including yolk-sac (YS), AGM, fetal liver (FL), umbilical cord blood (UCB) and adult peripheral blood (PB) mobilized HSPCs. These stage-specific HSPCs display differential intrinsic properties, such as metabolism, self-renewal, differentiating potentialities etc. We then generated highly co-related gene regulatory network (GRNs) modules underlying the differential HSC key properties. Particularly, we identified GRNs and key regulators controlling lymphoid potentiality, self-renewal as well as aerobic respiration in human HSCs. Introducing selected regulators promotes key HSC functions in HSPCs derived from human pluripotent stem cells. Therefore, GRNs underlying key intrinsic properties of human HSCs provide a valuable guide to generate fully functional HSCs in vitro.

Large-scale generation of IL-12 secreting macrophages from human pluripotent stem cells for cancer therapy.

Genetically engineered macrophages (GEMs) have emerged as an appealing strategy to treat cancers, but they are largely impeded by the cell availability and technical challenges in gene transfer. Here, we develop an efficient approach to generate large-scale macrophages from human induced pluripotent stem cells (hiPSCs). Starting with 1 T150 dish of 106 hiPSCs, more than 109 mature macrophages (iMacs) could be generated within 1 month. The generated iMacs exhibit typical macrophage properties such as phagocytosis and polarization. We then generate hiPSCs integrated with an IL-12 expression cassette in the AAVS1 locus to produce iMacs secreting IL-12, a strong proimmunity cytokine. hiPSC-derived iMacs_IL-12 prevent cytotoxic T cell exhaustion and activate T cells to kill different cancer cells. Furthermore, iMacs_IL-12 display strong antitumor effects in a T cell-dependent manner in subcutaneously or systemically xenografted mice of human lung cancer. Therefore, we provide an off-the-shelf strategy to produce large-scale GEMs for cancer therapy.

Autophagy is essential for human myelopoiesis.

Emergency myelopoiesis (EM) is essential in immune defense against pathogens for rapid replenishing of mature myeloid cells. During the EM process, a rapid cell-cycle switch from the quiescent hematopoietic stem cells (HSCs) to highly proliferative myeloid progenitors (MPs) is critical. How the rapid proliferation of MPs during EM is regulated remains poorly understood. Here, we reveal that ATG7, a critical autophagy factor, is essential for the rapid proliferation of MPs during human myelopoiesis. Peripheral blood (PB)-mobilized hematopoietic stem/progenitor cells (HSPCs) with ATG7 knockdown or HSPCs derived from ATG7-/- human embryonic stem cells (hESCs) exhibit severe defect in proliferation during fate transition from HSPCs to MPs. Mechanistically, we show that ATG7 deficiency reduces p53 localization in lysosome for a potential autophagy-mediated degradation. Together, we reveal a previously unrecognized role of autophagy to regulate p53 for a rapid proliferation of MPs in human myelopoiesis.