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Spinach is a crop of economic importance in the Wintergarden region of Texas, where increasing soil salinity, irrigation water restrictions, and heat stress challenge its production. Improving abiotic stress tolerance and resource use efficiency are important goals for sustainable agricultural production. Although the effect of humic substances (HS) on abiotic stress tolerance in spinach has been evaluated under single stress, such as heat, drought, or salinity, their impact under combined abiotic stresses is unknown. We hypothesized that solid humic substances would be effective in alleviating multifactorial abiotic stress in spinach, which we examined in our first experiment, and further hypothesized that salinity stress in spinach would occur after a threshold intensity but that humic substance applications would ameliorate stress intensity past this threshold, which we examined in our second experiment. Three-week-old spinach seedlings (Spinacia oleracea L. cv. ‘Seaside’) were grown using an automatic gravimetric watering system in a climate-controlled high tunnel where daily maximum temperatures exceeded 32 °C. In a factorial experiment, we applied HS (control and 1 % v/v HS media amendment), drought (100 % and 50 % field capacity), and salinity (25 mL of RO water or 100 mM NaCl every other day) treatments. HS and HS×Salinity treatments more than doubled shoot and root FW and DW, leaf area, root length, and root surface area compared to other stresses, indicating HS improved growth and stress tolerance. Improved growth was matched with improved resource use efficiency, as HS and HS×Salinity treated plants exhibited the greatest WUE. Drought stress also increased WUE relative to the control but lowered transpiration rate responses to VPD in contrasts to HS and HS×Salinity treated plants, which increased their transpiration rates in response to increasing VPD. Salinity treatments increased sodium content (Na+) in both shoots and roots. No HS effect was observed in shoot Na+ accumulation, but HS reduced Na+ in roots under the Drought×Salinity treatment. Strong interactions between drought and salinity were observed for shoot and root Na+, Na+/K+, and shoot K+, showing that spinach accumulates Na+ and reduces K+ when drought and salinity stress are combined. HS had no apparent effect on leaf metabolites. Drought and salinity differentially impacted MDA, proline, and antioxidant content and activities, while HS showed no effect. Drought stress significantly increased MDA and proline while reducing TPC, TFC, ABTS, and FRAP. Salinity stress significantly decreased MDA, TPC, ABTS, FICA, and FRAP. In conclusion, HS improved overall spinach growth and WUE while decreasing root Na accumulation, and subsequently enhancing spinach stress tolerance.

Abstract Background Immunotherapy has significantly advanced cancer treatments, but many patients do not respond to it, partly due to immunosuppressive mechanisms used by tumor cells. These cells employ immunosuppressive ligands to evade detection and elimination by the immune system. Therefore, the discovery and characterization of novel immunosuppressive ligands that facilitate immune evasion are crucial for developing more potent anti-cancer therapies. Methods We conducted gain-of-function screens using a CRISPRa (CRISPR activation) library that covered the entire human transmembrane sub-genome to identify surface molecules capable of hindering NK-mediated cytotoxicity. The immunosuppressive role and mechanism of MUC21 were validated using NK and T cell mediated cytotoxicity assays. Bioinformatics tools were employed to assess the clinical implications of mucin-21 (MUC21) in cancer cell immunity. Results Our genetic screens revealed that MUC21 expression on cancer cell surfaces inhibits both the cytotoxic activity of NK cells and antibody-dependent cellular cytotoxicity, but not affecting complement-dependent cytotoxicity. Additionally, MUC21 expression hinders T cell activation by impeding antigen recognition, thereby diminishing the effectiveness of the immune checkpoint inhibitor, anti-PD-L1. Moreover, MUC21 expression suppress the antitumor function of both CAR-T cells and CAR-NK cells. Mechanistically, MUC21 facilitates immune evasion by creating steric hindrance, preventing interactions between cancer and immune cells. Bioinformatics analysis revealed elevated MUC21 expression in lung cancer, which correlated with reduced infiltration and activation of cytotoxic immune cells. Intriguingly, MUC21 expression was higher in non-small cell lung cancer (NSCLC) tumors that were non-responsive to anti-PD-(L)1 treatment compared to responsive tumors. Conclusions These findings indicate that surface MUC21 serves as a potent immunosuppressive ligand, shielding cancer cells from NK and CD8+T cell attacks. This suggests that inhibiting MUC21 could be a promising strategy to improve cancer immunotherapy.

The demand for high-quality strawberries continues to grow, emphasizing the need for innovative agricultural practices to enhance both yield and fruit quality. In this context, the utilization of natural products, such as biostimulants, has emerged as a promising avenue for improving strawberry production while aligning with sustainable and eco-friendly agricultural approaches. This study explores the influence of a bacterial filtrate (BF), a vegetal-derived protein hydrolysate (PH), and a standard synthetic auxin (SA) on strawberry, investigating their effects on yield, fruit quality, mineral composition and metabolomics of leaves and fruits. Agronomic trial revealed that SA and BF significantly enhanced early fruit yield due to their positive influence on flowering and fruit set, while PH treatment favored a gradual and prolonged fruit set, associated with an increased shoot biomass and sustained production. Fruit quality analysis showed that PH-treated fruits exhibited an increase of firmness and soluble solids content, whereas SA-treated fruits displayed lower firmness and soluble solids content. The ionomic analysis of leaves and fruits indicated that all treatments provided sufficient nutrients, with heavy metals within regulatory limits. Metabolomics indicated that PH stimulated primary metabolites, while SA and BF directly affected flavonoid and anthocyanin biosynthesis, and PH increased fruit quality through enhanced production of beneficial metabolites. This research offers valuable insights for optimizing strawberry production and fruit quality by harnessing the potential of natural biostimulants as viable alternative to synthetic compounds.

Abstract Adoptive cell therapy (ACT) with antigen‐specific T cells is a promising treatment approach for solid cancers. Interleukin‐2 (IL‐2) has been utilized in boosting the efficacy of ACT. However, the clinical applications of IL‐2 in combination with ACT is greatly limited by short exposure and high toxicities. Herein, a complex coacervate was designed to intratumorally deliver IL‐2 in a sustained manner and protect against proteolysis. The complex coacervate consisted of fucoidan, a specific IL‐2 binding glycosaminoglycan, and poly‐l‐lysine, a cationic counterpart (FPC2). IL‐2‐laden FPC2 exhibited a preferential bioactivity in ex vivo expansion of CD8+T cells over Treg cells. Additionally, FPC2 was embedded in pH modulating injectable gel (FPC2‐IG) to endure the acidic tumor microenvironment. A single intratumoral administration of FPC2‐IG‐IL‐2 increased expansion of tumor‐infiltrating cytotoxic lymphocytes and reduced frequencies of myeloid populations. Notably, the activation and persistency of tumor‐reactive T cells were observed only in the tumor site, not in the spleen, confirming a localized effect of FPC2‐IG‐IL‐2. The immune‐favorable tumor microenvironment induced by FPC2‐IG‐IL‐2 enabled adoptively transferred TCR‐engineered T cells to effectively eradicate tumors. FPC2‐IG delivery system is a promising strategy for T‐cell‐based immunotherapies.

Introduction: Importance of inferomedial supporting screws in preventing varus collapse has been investigated for the proximal humerus fracture. However, few studies reported the results of osteoporotic complex fracture. This study aimed to demonstrate the stress distribution pattern, particularly in osteoporotic 3-part proximal humerus fractures involving greater tuberosity (GT) with different screw configurations. Materials and methods: Using the computed tomography (CT) images of 2 patients, who had osteoporosis and the other had normal bone density, 3-part fractures involving the GT, without medial support were reconstructed. To reflect the osteoporosis or real bone density, Hounsfield unit of CT scans were utilized. A force of 200 N was applied in 30° varus direction. The proximal screws were set in 2 ways: 6 screws without inferomedial supporting screws and 9 screws with inferomedial supporting screws. Qualitative and quantitative analysis of internal stress distribution were performed. Results: The most proximal part area near humeral head vertex and near the 1st screw’s passage and tip had more stress concentrated in osteoporotic 3-part fractures. The stress distribution around the proximal screws was found near the GT fracture line and its lateral side, where the local max values located. Inferomedial supporting screws decreased these effects by changing the points to medial side from the GT. The ratio in osteoporotic bone model decreased to that in normal bone model when inferomedial supporting screws were applied (normal bone, 2.97%–1.30%; osteoporosis bone, 4.76%–1.71%). Conclusions: In osteoporotic 3-part proximal humerus fracture, the stress distribution was concentrated on the area near the humeral vertex, 1st row screw tips, and lateral side region from the GT fracture line. Moreover, inferomedial supporting screws ensured that the stress distribution is similar to that in normal bone setting, particularly in osteoporotic condition.

Plant-derived protein hydrolysates (PHs) are gaining global interest for their sustainability and positive effects on crops under abiotic stresses. However, the long-term effects of PHs on the yield and quality of greenhouse crops have not been described. Romaine lettuce (Lactuca sativa L.) and Micro-Tom tomato (Solanum lycopersicum L.) were grown with commercial growing media in 1 L pots and fertigated with four N levels (2, 5, 10, and 15 mM). PH (0 or 3 g/L) was applied as a foliar spray (PH-F) or root drench (PH-R) once every week. Compared to PH-F, PH-R effectively stimulated the yield, photosynthesis, water-use efficiency, chlorophyll contents, and antioxidant activities, and compounds regardless of N levels and species. Increasing the N level led to a total dry weight gain, and PH-R enhanced the lettuce shoot dry weight (+31%) and tomato fruit dry weight (+22%). PH-R also increased the fresh marketable yield of lettuce (+21%) and tomato (+32%). The increasing N level decreased antioxidant parameters in lettuce leaves, not in tomato fruits, whereas PH-R improved them in both species. PH-R significantly enhanced the N use and uptake efficiency. Taken together, our results suggested that the addition of PH-R effectively increased the N uptake and subsequently increased the lettuce and tomato yield and quality regardless of N levels.

The mucin (MUC) family is a group of highly glycosylated macromolecules that are abundantly expressed in mammalian epithelial cells. MUC proteins contribute to the formation of the mucus barrier and thus have protective functions against infection. Interestingly, some MUC proteins are aberrantly expressed in cancer cells and are involved in cancer development and progression, including cell growth, proliferation, the inhibition of apoptosis, chemoresistance, metabolic reprogramming, and immune evasion. With their unique biological and structural features, MUC proteins have been considered promising therapeutic targets and also biomarkers for human cancer. In this review, we discuss the biological roles of the transmembrane mucins MUC1 and MUC16 in the context of hallmarks of cancer and current efforts to develop MUC1- and MUC16-targeted therapies.

For patients with chronic lower respiratory disease, hypobaric hypoxia at a high altitude is considered a risk factor for mortality. However, the effects of residing at moderately high altitudes remain unclear. We investigated the association between moderate altitude and chronic lower respiratory disease mortality. In particular, we examined the lower 48 United States counties for age-adjusted chronic lower respiratory disease mortality rates, altitude, and socioeconomic factors, including tobacco use, per capita income, population density, sex ratio, unemployment, poverty, and education between 1979 and 1998. The socioeconomic factors were incorporated into the correlation analysis as potential covariates. Considerable positive (R = 0.235; P

Factories of the future are foreseen to evolve into smart factories with autonomous and adaptive manufacturing processes. However, the increasing complexity of the network of manufacturing processes is expected to complicate the rapid detection of process anomalies in real time. This paper proposes an architecture framework and method for the implementation of the Scalable On-line Anomaly Detection System (SOADS), which can detect process anomalies via real-time processing and analyze large amounts of process execution data in the context of autonomous and adaptive manufacturing processes. The design of this system architecture framework entailed the derivation of standard subsequence patterns using the PrefixSpan algorithm, a sequential pattern algorithm. The anomalies of the real-time event streams and derived subsequence patterns were scored using the Smith-Waterman algorithm, a sequence alignment algorithm. The excellence of the proposed system was verified by measuring the time for deriving subsequence patterns and by obtaining the anomaly scoring time from large event logs. The proposed system succeeded in large-scale data processing and analysis, one of the requirements for a smart factory, by using Apache Spark streaming and Apache Hbase, and is expected to become the basis of anomaly detection systems of smart factories.

In actual vehicle operation, the turbocharger turbine operates at various temperatures, inlet, and backpressure conditions, unlike compressors. The flow rate characteristics of the turbine are generally evaluated under certain conditions using an assembled turbocharger with a compressor and a turbine and a hot gas bench from the turbocharger manufacturer. Flow rate characteristics are also presented as the reduced mass flow rate to correct the flow rate characteristics according to the turbine inlet temperature and pressure. Therefore, the turbine mass flow rate seen in many engine development cases and studies—including the analysis of the turbine performance and characteristics, engine model configuration, and matching of the engine and turbocharger—is calculated according to the reduced turbine mass flow rate performance and turbine inlet temperature and pressure obtained through hot gas bench experiments under certain conditions. However, the performance of the reduced turbine mass flow rate is influenced by the compressor power conditions, and additional correction of the reduced turbine mass flow rate is required when the turbine inlet temperature and turbine backpressure differ from the reference test conditions, such as the hot gas bench test conditions. In this study, the effect of the turbine inlet temperature and turbine backpressure on the performance of the reduced turbine mass flow rate were examined based on the power balance relationship between the compressor and turbine of an automotive turbocharger. The principle of its correction is also presented.

Plant-derived protein biostimulants exhibit hormone-like activities promoting plant growth and yield, yet detailed investigations on hormonal function have remained limited. This study was conducted to investigate the effects of vegetal-derived-biostimulant on morphological and metabolic changes in cuttings of three herbaceous species demonstrating different rooting ability, basil (Ocimum basilicum L.), tomato (Solanum lycopersicum L.), and chrysanthemum (Chrysanthemum indicum L.), in comparison to auxin. Unrooted cuttings were applied with or without biostimulant (100, 1000, 5000, and 10,000 mg L−1) or auxin [1% indole-3-butyric acid (IBA) plus 0.5% 1-naphthaleneacetic acid (NAA); 100, 200, 300, and 500 mg L−1] as a basal quick-dip, stuck into inert media, and evaluated at 20 days after placement under intermittent mist. Both compounds increased adventitious rooting in all cuttings. Biostimulant required a significantly higher threshold for a series of adventitious rooting responses than auxin, and the maximum effectiveness was achieved at 5000 mg L−1 for biostimulant and 100, 200, and 300 mg L−1 for auxin in basil, tomato, and chrysanthemum, respectively. Adventitious rooting responses (dry mass and length) to biostimulant showed a gradual logarithmic rise as a function of increasing dosages, which was not in agreement with biphasic dose-response of auxin. Biostimulant significantly increased or tended to increase fine roots in all tested cuttings, which was not consistent with auxin. Relatively high levels of endogenous brassinosteroids (BRs) were present in non-treated cuttings of basil, tomato, and chrysanthemum in decreasing order. Both compounds had no effects or concomitantly increased or decreased BR levels in plant tissues, with fewer effects on basil and tomato, containing high BR levels, but more prominent effects on chrysanthemum, containing relatively low BR levels. Contrasting effects of biostimulant and auxin were found in antioxidant activities, which were promoted by biostimulant but inhibited by auxin either in roots or shoots. These results indicate that the hormonal effects of vegetal-derived biostimulant are primarily exerted by BR-mediated processes while involving interaction with auxin. Both the biostimulant-derived BRs and auxin were suggested to modulate endogenous BR pool via overlapping and interdependent regulatory functions, inducing morphological and metabolic changes during adventitious rooting of cuttings in a plant species-specific manner.