Altering biomolecular condensates as a potential mechanism that mediates cannabidiol effect on glioblastoma.

Glioblastoma (GBM) is an extremely aggressive primary brain tumor with poor prognosis, short survival time post-diagnosis and high recurrence. Currently, no cure for GBM exists. The identification of an effective therapeutic modality for GBM remains a high priority amongst medical professionals and researches. In recent studies, inhalant cannabidiol (CBD) has demonstrated promise in effectively inhibiting GBM tumor growth. However, exactly how CBD treatment affects the physiology of these tumor cells remains unclear. Stress granules (SG) (a sub-class of biomolecular condensates (BMC)) are dynamic, membrane-less intracellular microstructures which contain proteins and nucleic acids. The formation and signaling of SGs and BMCs plays a significant role in regulating malignancies. This study investigates whether inhaled CBD may play an intervening role towards SGs in GBM tumor cells. Integrated bioinformatics approaches were preformed to gain further insights. This includes use of Immunohistochemistry and flow cytometry to measure SGs, as well as expression and phosphorylation of eukaryotic initiation factor-2α (eIF2α). The findings of this study reveal that CBD receptors (and co-regulated genes) have the potential to play an important biological role in the formation of BMCs within GBM. In this experiment, CBD treatment significantly increased the volume of TIAR-1. This increase directly correlated with elevation in both eIF2α expression and p-eIF2α in CBD treated tissues in comparison to the placebo group (p < 0.05). These results suggest that inhalant CBD significantly up-regulated SGs in GBM, and thus support a theory of targeting BMCs as a potential therapeutic substrate for treating GBM.

Novel Alkaloids from Aspergillus fumigatus VDL36, an Endophytic Fungus Associated with Vaccinium dunalianum.

Eleven alkaloids (1-11) including seven new ones, 1-7, were isolated from the solid fermentation of Aspergillus fumigatus VDL36, an endophytic fungus isolated from the leaves of Vaccinium dunalianum Wight (Ericaceae), a perennial evergreen shrub distributed across the Southwest regions of China, Myanmar, and Vietnam. Their structures were elucidated on the basis of extensive spectroscopic methods. The isolates were evaluated for in vitro antifungal activities against five phytopathogenic fungi (Fusarium oxysporum, Coriolus versicolor, Fusarium solani, Botrytis cinerea, Fusarium graminearum). As a result, the new compounds fumigaclavine I (1), 13-ethoxycyclotryprostatin A (5), 13-dehydroxycyclotryprostatin A (6), and 12ß-hydroxy-13-oxofumitremorgin C (7) exhibited antifungal activities with MIC values of 7.8-62.5 µg/mL which were comparable to the two positive controls ketoconazole (MIC = 7.8-31.25 µg/mL) and carbendazim (MIC = 1.95-7.8 µg/mL). Furthermore, compounds 1 and 5 demonstrated potent protective and curative effects against the tomato gray mold in vivo. Preliminary structure-activity relationships of the tested indole diketopiperazine alkaloids indicate that the introduction of a substituent group at position C-13 enhances their biological activities.

The role and transcriptomic mechanism of cell wall in the mutual antagonized effects between selenium nanoparticles and cadmium in wheat.

Selenium nanoparticles (SeNPs) has been reported as a beneficial role in alleviating cadmium (Cd) toxicity in plant. However, underlying molecular mechanisms about SeNPs reducing Cd accumulation and alleviating Cd toxicity in wheat are not well understood. A hydroponic culture was performed to evaluate Cd and Se accumulation, cell wall components, oxidative stress and antioxidative system, and transcriptomic response of wheat seedlings after SeNPs addition under Cd stress. Results showed that SeNPs application notably reduced Cd concentration in root and in shoot by 56.9% and 37.3%, respectively. Additionally, SeNPs prompted Cd distribution in root cell wall by 54.7%, and increased lignin, pectin and hemicellulose contents by regulating cell wall biosynthesis and metabolism-related genes. Further, SeNPs alleviated oxidative stress caused by Cd in wheat through signal transduction pathways. We also observed that Cd addition reduced Se accumulation by downregulating the expression level of aquaporin 7. These results indicated that SeNPs alleviated Cd toxicity and reduced Cd accumulation in wheat, which were associated with the synergetic regulation of cell wall biosynthesis pathway, uptake transporters, and antioxidative system via signaling pathways.

Preparation and functional properties of rice bran globulin-chitooligosaccharide-quercetin-resveratrol covalent complex.

BACKGROUND: As the major protein (approximately 36%) in rice bran, globulin exhibits excellent foaming and emulsifying properties, endowing its useful application as a foaming and emulsifying agent in the food industry. However, the low water solubility restricts its commercial potential in industrial applications. The present study aimed to improve this protein's processing and functional properties. RESULTS: A novel covalent complex was fabricated by a combination of the Maillard reaction and alkaline oxidation using rice bran globulin (RBG), chitooligosaccharide (C), quercetin (Que) and resveratrol (Res). The Maillard reaction improved the solubility, emulsifying and foaming properties of RBG. The resultant glycosylated protein was covalently bonded with quercetin and resveratrol to form a (RBG-C)-Que-Res complex. (RBG-C)-Que-Res exhibited higher thermal stability and antioxidant ability than the native protein, binary globulin-chitooligosaccharide or ternary globulin-chitooligosaccharide-polyphenol (only containing quercetin or resveratrol) conjugates. (RBG-C)-Que-Res exerted better cytoprotection against the generation of malondialdehyde and reactive oxygen species in HepG2 cells, which was associated with increased activities of antioxidative enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) through upregulated genes SOD1, CAT, GPX1 (i.e. gene for glutathione peroxidase-1), GCLM (i.e. gene for glutamate cysteine ligase modifier subunit), SLC1A11 (i.e. gene for solute carrier family 7, member 11) and SRXN1 (i.e. gene for sulfiredoxin-1). The anti-apoptotic effect of (RBG-C)-Que-Res was confirmed by the downregulation of caspase-3 and p53 and the upregulation of B-cell lymphoma-2 gene expression. CONCLUSION: The present study highlights the potential of (RBG-C)-Que-Res conjugates as functional ingredients in healthy foods. © 2024 Society of Chemical Industry.

Overcoming Thermal Quenching in X-ray Scintillators through Multi-Excited State Switching.

X-ray scintillators have gained significant attention in medical diagnostics and industrial applications. Despite their widespread utility, scintillator development faces a significant hurdle when exposed to elevated temperatures, as it usually results in reduced scintillation efficiency and diminished luminescence output. Here we report a molecular design strategy based on a hybrid perovskite (TpyBiCl5) that overcomes thermal quenching through multi-excited state switching. The structure of perovskite provides a platform to modulate the luminescence centers. The rigid framework constructed by this perovskite structure stabilized its triplet states, resulting in TpyBiCl5 exhibiting an approximately 12 times higher (45 % vs. 3.8 %) photoluminescence quantum yield of room temperature phosphorescence than that of its organic ligand (Tpy). Most importantly, the interactions between the components of this perovskite enable the mixing of different excited states, which has been revealed by experimental and theoretical investigations. The TpyBiCl5 scintillator exhibits a detection limit of 38.92 nGy s-1 at 213 K and a detection limit of 196.31 nGy s-1 at 353 K through scintillation mode switching between thermally activated delayed fluorescence and phosphorescence. This work opens up the possibility of solving the thermal quenching in X-ray scintillators by tuning different excited states.

A generalizable sensing platform based on molecularly imprinted polymer-aptamer double recognition and nanoenzyme assisted photoelectrochemical-colorimetric dual-mode detection.

Developing highly sensitive and selective methods that incorporate specific recognition elements is crucial for detecting small molecules because of the limited availability of small molecule antibodies and the challenges in obtaining sensitive signals. In this study, a generalizable photoelectrochemical-colorimetric dual-mode sensing platform was constructed based on the synergistic effects of a molecularly imprinted polymer (MIP)-aptamer sandwich structure and nanoenzymes. The MIP functionalized peroxidase-like Fe3O4 (Fe3O4@MIPs) and alkaline phosphatase mimic Zr-MOF labeled aptamer (Zr-mof@Apt) were used as the recognition elements. By selectively accumulating dibutyl phthalate (DBP), a small molecule target model, on Fe3O4@MIPs, the formation of Zr-MOF@Apt-DBP- Fe3O4@MIPs sandwich structure was triggered. Fe3O4@MIPs oxidized TMB to form blue-colored oxTMB. However, upon selective accumulation of DBP, the catalytic activity of Fe3O4@MIPs was inhibited, resulting in a lighter color that was detectable by the colorimetric method. Additionally, Zr-mof@Apt effectively catalyzed the hydrolysis of L-Ascorbic acid 2-phosphate sesquimagnesium salt hydrate (AAPS), generating ascorbic acid (AA) that could neutralize the photogenerated holes to decrease the photocurrent signals for PEC sensing and reduce oxTMB for colorimetric testing. The dual-mode platform showed strong linearity for different concentrations of DBP from 1.0 pM to 10 µM (PEC) and 0.1 nM to 0.5 µM (colorimetry). The detection limits were 0.263 nM (PEC) and 30.1 nM (colorimetry) (S/N = 3), respectively. The integration of dual-signal measurement mode and sandwich recognition strategy provided a sensitive and accurate platform for the detection of small molecules.

Sarcopenia is associated with leukopenia in urothelial carcinoma patients who receive tislelizumab combined with gemcitabine and cisplatin therapy.

BACKGROUND: In the era of combination therapy, there has been limited research on body composition. Specific body composition, such as sarcopenia, possesses the potential to serve as a predictive biomarker for toxic effects and clinical response in patients with urothelial carcinoma (UC) undergoing tislelizumab combined with gemcitabine and cisplatin (T + GC). MATERIALS AND METHODS: A total of 112 UC patients who received T + GC were selected at the Affiliated Hospital of Xuzhou Medical University from April 2020 to January 2023. Baseline patient characteristics and detailed hematological parameters were collected using the electronic medical system and laboratory examinations. The computed tomography images of patients were analyzed to calculate psoas muscle mass index (PMI). We evaluated the association between sarcopenia (PMI < 4.5 cm2/m2 in men; PMI < 3.3 cm2/m2 in women) and both hematological toxicity and tumor response. RESULTS: Overall, of the 112 patients (65.2% male, median age 56 years), 43 (38.4%) were defined as sarcopenia. Patients with sarcopenia were notably older (p = 0.037), more likely to have hypertension (p = 0.009), and had poorer ECOG-PS (p = 0.027). Patients with sarcopenia were more likely to develop leukopenia (OR 2.969, 95% CI 1.028-8.575, p = 0.044) after receiving at least two cycles of T + GC. However, these significant differences were not observed in thrombocytopenia and anemia. There were no significant differences in the tumor response and grade 3-4 hematological toxicity between patients with sarcopenia and those without sarcopenia. CONCLUSIONS: Patients with sarcopenia were more likely to develop leukopenia after receiving T + GC. There were no notable alterations observed in relation to anemia or thrombocytopenia. No significant difference was found between the sarcopenia group and non-sarcopenia group in terms of tumor response and grade 3-4 hematological toxicity.

Tissue-engineered bone construct promotes early osseointegration of implants with low primary stability in oversized osteotomy.

OBJECTIVES: To evaluate the histological parameters and bone mechanical properties around implants with low primary stability (PS) in grafted bone substitutes within an oversized osteotomy. MATERIALS AND METHODS: An oversized osteotomy penetrating the double cortical bone layers was made on both femora of 24 New Zealand white rabbits. Bilaterally in the femur of all animals, 48 implants were installed, subdivided into four groups, corresponding to four prepared tissue-engineering bone complexes (TEBCs), which were placed between the implant surface and native bone wall: A: tricalcium phosphate ß (TCP-ß); B: autologous adipose derived-stem cells with TCP-ß (ASCs/TCP-ß); C: ASCs transfected with the enhanced-GFP gene with TCP-ß (EGFP-ASCs/TCP-ß); D: ASCs transfected with the BMP-2 gene with TCP-ß (BMP2-ASCs/TCP-ß). Trichrome fluorescent labeling was conducted. Animals were sacrificed after eight weeks. The trichromatic fluorescent labeling (%TFL), area of new bone (%NB), residual material (%RM), bone-implant contact (%BIC), and the removal torque force (RTF, N/cm) were assessed. RESULTS: ASCs were successfully isolated from adipose tissue, and the primary ASCs were induced into osteogenic, chondrogenic, and adipogenic differentiation. The BMP-2 overexpression of ASCs sustained for ten days and greatly enhanced the expression of osteopontin (OPN). At eight weeks post-implantation, increased %NB and RTF were found in all groups. The most significant value of %TFL, %BIC and lowest %RM was detected in group D. CONCLUSION: The low PS implants osseointegrate with considerable new bone in grafted TEBCs within an oversized osteotomy. Applying BMP-2 overexpressing ASCs-based TEBC promoted earlier osseointegration and more solid bone mechanical properties on low PS implants. Bone graft offers a wedging effect for the implant with low PS at placement and promotes osteogenesis on their surface in the healing period.

Variations in Cadmium and Lead Bioaccessibility in Wheat Cultivars and Their Correlations with Nutrient Components.

To reduce the health risks of exposure to Cd and Pb in wheat, a field experiment was conducted to investigate the differences in Cd and Pb bioaccessibility among the grains of 11 wheat cultivars and their relationships with the nutrient compositions of grains. The grain concentrations (Cd: 0.14-0.56 mg kg-1, Pb: 0.08-0.39 mg kg-1) and bioaccessibility (5.28-57.43% and 0.72-7.72% for Cd and Pb in the intestinal phase, respectively) of Cd and Pb differed significantly among the 11 cultivars. A safe wheat cultivar (Shannong16) with a relatively low health risk and the lowest grain Cd and Pb concentrations was selected. Ca, Mg, phytate, and methionine played key roles in affecting Cd and Pb bioaccessibility in wheat, with Ca and phytate significantly negatively correlated with Cd and Pb bioaccessibility. These findings can be used to optimize the selection strategy for safe wheat cultivars for healthy grain production in Cd-polluted farmland.

Sample size and power calculations for causal mediation analysis: A Tutorial and Shiny App.

When designing a study for causal mediation analysis, it is crucial to conduct a power analysis to determine the sample size required to detect the causal mediation effects with sufficient power. However, the development of power analysis methods for causal mediation analysis has lagged far behind. To fill the knowledge gap, I proposed a simulation-based method and an easy-to-use web application ( https://xuqin.shinyapps.io/CausalMediationPowerAnalysis/ ) for power and sample size calculations for regression-based causal mediation analysis. By repeatedly drawing samples of a specific size from a population predefined with hypothesized models and parameter values, the method calculates the power to detect a causal mediation effect based on the proportion of the replications with a significant test result. The Monte Carlo confidence interval method is used for testing so that the sampling distributions of causal effect estimates are allowed to be asymmetric, and the power analysis runs faster than if the bootstrapping method is adopted. This also guarantees that the proposed power analysis tool is compatible with the widely used R package for causal mediation analysis, mediation, which is built upon the same estimation and inference method. In addition, users can determine the sample size required for achieving sufficient power based on power values calculated from a range of sample sizes. The method is applicable to a randomized or nonrandomized treatment, a mediator, and an outcome that can be either binary or continuous. I also provided sample size suggestions under various scenarios and a detailed guideline of app implementation to facilitate study designs.

Causal moderated mediation analysis: Methods and software.

Research questions regarding how, for whom, and where a treatment achieves its effect on an outcome have become increasingly valued in substantive research. Such questions can be answered by causal moderated mediation analysis, which assesses the heterogeneity of the mediation mechanism underlying the treatment effect across individual and contextual characteristics. Various moderated mediation analysis methods have been developed under the traditional path analysis/structural equation modeling framework. One challenge is that the definitions of moderated mediation effects depend on statistical models of the mediator and the outcome, and no solutions have been provided when either the mediator or the outcome is binary, or when the mediator or outcome model is nonlinear. In addition, it remains unclear to empirical researchers how to make causal arguments of moderated mediation effects due to a lack of clarifications of the underlying assumptions and methods for assessing the sensitivity to violations of the assumptions. This article overcomes the limitations by developing general definition, identification, estimation, and sensitivity analysis for causal moderated mediation effects under the potential outcomes framework. We also developed a user-friendly R package moderate.mediation ( https://cran.r-project.org/web/packages/moderate.mediation/index.html ) that allows applied researchers to easily implement the proposed methods and visualize the initial analysis results and sensitivity analysis results. We illustrated the application of the proposed methods and the package implementation with a re-analysis of the National Evaluation of Welfare-to-Work Strategies (NEWWS) Riverside data.

Erratum: Author correction to "Tumor-microenvironment activated duplex genome-editing nanoprodrug for sensitized near-infrared titania phototherapy" Acta Pharm Sin B (2022) 4224-4234

[This corrects the article DOI: 10.1016/j.apsb.2022.06.016.].

Mediation Analysis using Semi-parametric Shape-Restricted Regression with Applications.

Often linear regression is used to perform mediation analysis. However, in many instances, the underlying relationships may not be linear, as in the case of placentalfetal hormones and fetal development. Although, the exact functional form of the relationship may be unknown, one may hypothesize the general shape of the relationship. For these reasons, we develop a novel shape-restricted inference-based methodology for conducting mediation analysis. This work is motivated by an application in fetal endocrinology where researchers are interested in understanding the effects of pesticide application on birth weight, with human chorionic gonadotropin (hCG) as the mediator. We assume a practically plausible set of nonlinear effects of hCG on the birth weight and a linear relationship between pesticide exposure and hCG, with both exposure-outcome and exposure-mediator models being linear in the confounding factors. Using the proposed methodology on a population-level prenatal screening program data, with hCG as the mediator, we discovered that, while the natural direct effects suggest a positive association between pesticide application and birth weight, the natural indirect effects were negative.

The addition of tislelizumab to gemcitabine and cisplatin chemotherapy increases thrombocytopenia in patients with urothelial carcinoma: A single-center study based on propensity score matching.

PURPOSE: Whether the addition of tislelizumab to gemcitabine and cisplatin (GC) chemotherapy increases the incidence of myelosuppression has not been well established. This study identified the risk factors for the development of myelosuppression in patients with urothelial carcinoma (UC) after receiving GC chemotherapy with or without tislelizumab. MATERIALS AND METHODS: We enrolled 192 UC patients who received GC with or without tislelizumab at the Affiliated Hospital of Xuzhou Medical University between July 2014 and November 2022. Patient baseline characteristics were included in the statistical analyses after adjusting for previously reported risk factors affecting survival using propensity score matching (1:1). Binary logistic regression analysis was used to identify the risk factors associated with posttreatment myelosuppression. RESULTS: A total of 192 patients were enrolled, of whom 96 were treated with tislelizumab plus gemcitabine and cisplatin (T + GC) and 96 with GC alone. The incidence of leukopenia, anemia, and thrombocytopenia of any grade was 50.0%, 70.8%, and 42.7%, respectively, in the T + GC group and 41.7%, 72.9%, and 20.8%, respectively, in the GC group. In multivariate analysis, patients aged over 70 years (OR = 2.486, 95% CI: 1.067-5.792, p = 0.035) and those who received T + GC (OR = 3.119, 95% CI: 1.576-6.173, p = 0.001) were more likely to develop thrombocytopenia. Patients aged over 70 years (OR = 3.213, 95% CI: 1.254-8.237, p = 0.015) were more likely to develop anemia, and patients with renal insufficiency (OR = 2.105, 95% CI: 1.035-4.280, p = 0.040) were more likely to develop leukopenia. Eventually, 99 (51.6%) patients with UC successfully completed all the treatment cycles. CONCLUSIONS: This study demonstrates that the addition of tislelizumab to GC chemotherapy led to a considerable increase in the occurrence of thrombocytopenia, whereas no significant changes were observed regarding anemia or leukopenia. It is crucial to fully inform patients at increased risk for myelosuppression of potential risks and closely monitor changes in their blood routines.

[Mercury species analysis and tissue distribution in rats after continuous administration of Cinnabaris].

Cinnabaris is a traditional Chinese medicine(TCM) commonly used for sedation and tranquilization in clinics, and its safety has always been a concern. This study intends to investigate the species and tissue distribution of mercury in rats after continuous administration of Cinnabaris. In the experiment, 30 rats were randomly divided into the control group(equivalent to 0.5% carboxy-methyl cellulose sodium), low-dose Cinnabaris group(0.2 g·kg~(-1)), high-dose Cinnabaris group(2 g·kg~(-1)), pseudogerm-free control group(equivalent to 0.5% sodium carboxymethyl cellulose), and pseudogerm-free Cinnabaris group(2 g·kg~(-1)). They were orally administered for 30 consecutive days. Ultrasound-assisted acid extraction method combined with high performance liquid chromatography and inductively coupled plasma-mass spectrometry(HPLC-ICP-MS) was adopted to determine inorganic mercury [Hg(Ⅱ)], methylmercury(MeHg), and ethylmercury(EtHg) in different tissue, plasma, urine, and feces of rats. The optimal detection conditions and extraction methods were optimized, and the linearity(R~2>0.999 3), precision(RSD<7.0%), and accuracy(spike recoveries ranged from 73.05% to 109.5%) of all the mercury species were satisfied, meeting the requirements of analysis. The results of mercury species detection showed that Hg(Ⅱ) was detected in all the tissue of the five experimental groups, and the main accumulating organs were the intestinal tract, stomach, and kidney. MeHg existed at a low concentration in most tissue, and EtHg was not detected in all groups. In addition, pathological examination results showed that hepatocyte vacuolar degeneration, loose cytoplasm, light staining, and mononuclear cell infiltration were observed in the high-dose Cinnabaris group, low-dose Cinnabaris group, and pseudogerm-free Cinnabaris group, with slightly milder lesions in the low-dose Cinnabaris group. Hydrous degeneration of renal tubular epithelium could be seen in the high-dose Cinnabaris group and pseudogerm-free Cinnabaris group, but there was no significant difference between the other groups and the control group. No abnormal changes were found in the brain tissue of rats in each group. This paper studied the different mercury species and tissue distribution in normal and pseudogerm-free rats after continuous administration of Cinnabaris for 30 days and clarified its effects on the tissue structure of the liver, kidney, and brain, which provided supporting evidence for the safety evaluation of Cinnabaris.

Negative capacitors and inductors enabling wideband waveguide metatronics.

Waveguide metatronics, known as an advanced platform of metamaterial-inspired circuits, provides a promising paradigm for millimeter-wave and terahertz integrated circuits in future fifth/sixth generation (5/6G) communication systems. By exploiting the structural dispersion properties of waveguides, a lumped type of waveguide integrated elements and circuits could be developed in deep subwavelength scales with intrinsic low loss and low crosstalk. In this study, we focus on constructing negative capacitors and inductors for waveguide metatronics, effectively expanding the operating frequency range of waveguide integrated circuits. The incorporation of negative elements enables wideband impedance matching in waveguide, which have been both theoretically explored and experimentally validated within the waveguide metatronics paradigm. Furthermore, we have demonstrated that the negative elements can also be realized in the optical domain through the utilization of a silicon waveguide with photonic crystal cladding, indicating the feasibility and universality of wideband waveguide metatronics. The negative lumped elements could boost the progress of the waveguide metatronic technique, achieving superior performance on the conventional lumped circuits within waveguides that solely rely on positive elements.

Selenate reduced wheat grain cadmium accumulation by inhibiting cadmium absorption and increasing root cadmium retention.

Selenium (Se) fertilizer has been recently used to reduce cadmium (Cd) accumulation in plant. A pot culture was performed to analyze Cd uptake, translocation, and distribution in wheat plants during the reproductive growth period in a Cd-contaminated soil after selenate was applied to the soil, and a hydroponic culture was carried out to investigate the effects of selenate application on Cd2+ influx, subcellular Cd distribution, and Cd accumulation in wheat seedlings. Results showed that selenate application had no significant effect on DTPA-Cd and Cd fraction in soil. The application of selenate greatly inhibited the whole-plant Cd absorption by 14%-23%. In addition, selenate prompted the retention of Cd in root by increasing the Cd distribution in the vacuole, which reduced the root-to-shoot Cd translocation by 18%-53%. The application of selenate increased the Cd concentration in nodes, inhibited Cd remobilization from nutritive organs to grain, and ultimately reduced Cd accumulation in wheat grain. Further, heading to grain filling was the key growth stage for exogenous selenate to regulate grain Cd accumulation. In summary, soil selenate application is an effective method to reduce grain Cd concentration in wheat, which provided scientific basis for remediation of Cd-contaminated soil.

Mercapto-palygorskite efficiently immobilizes cadmium in alkaline soil and reduces its accumulation in wheat plants: A field study.

Cadmium (Cd) contamination in wheat fields has become a major environmental issue in many regions of the world. Mercapto-palygorskite (MPAL) is a high-performance amendment that can effectively immobilize Cd in alkaline wheat soil. However, MAPL as an in-situ Cd immobilization strategy for alkaline wheat soil remains to be evaluated on a field-scale and the underlying mechanisms requires further evaluation. Here, MPAL were used as soil amendment to evaluate their immobilization efficiency on Cd-contaminated alkaline soil in the field experiments. The field experiments showed that MPAL application significantly reduced wheat grain Cd concentration from 0.183 mg/kg to 0.056 mg/kg, with Cd concentration in wheat grain treated with MPAL all falling below the limit value of 0.1 mg/kg as defined in China's food safety standard (GB 2762-2022). The maximal immobilization efficiency of MPAL on soil Cd figured out by diethylenetriaminepentaacetic acid (DTPA) extraction was 61.5%. The mechanisms involved in Cd immobilization by MPAL were mainly related to the enhanced sorption of Cd onto Fe oxides, and the removal of amorphous or free Fe oxides from soil had a substantial impact on Cd immobilization efficiency by MPAL. Furthermore, the antagonistic effect between Mn and Cd uptake may also contribute to the reduction of wheat Cd accumulation after MPAL application. The current research can provide theoretical and technical support for the large-scale application of MPAL in Cd-contaminated wheat fields.

Quercetin Ameliorates Deoxynivalenol-Induced Intestinal Injury and Barrier Dysfunction Associated with Inhibiting Necroptosis Signaling Pathway in Weaned Pigs.

Quercetin (Que) is a flavonol compound found in plants, which has a variety of biological activities. Necroptosis, a special form of programmed cell death, plays a vital role in the development of many gastrointestinal diseases. This study aimed to explore whether Que could attenuate the intestinal injury and barrier dysfunction of piglets after deoxynivalenol (DON) exposure through modulating the necroptosis signaling pathway. Firstly, twenty-four weaned piglets were used in a 2 × 2 factorial design and the main factors, including Que (basal diet or diet supplemented with 100 mg/kg Que) and DON exposure (control feed or feed contaminated with 4 mg/kg DON). After feeding for 21 d, piglets were killed for samples. Next, the intestinal porcine epithelial cell line (IPEC-1) was pretreated with or without Que (10 µmol/mL) in the presence or absence of a DON challenge (0.5 µg/mL). Dietary Que increased the body weight, average daily gain, and average daily feed intake (p < 0.05) through the trial. Que supplementation improved the villus height, and enhanced the intestinal barrier function (p < 0.05) indicated by the higher protein expression of occludin and claudin-1 (p < 0.05) in the jejunum of the weaned piglets after DON exposure. Dietary Que also down-regulated the protein abundance of total receptor interacting protein kinase 1 (t-RIP1), phosphorylated RIP1 (p-RIP1), p-RIP3, total mixed lineage kinase domain-like protein (t-MLKL), and p-MLKL (p < 0.05) in piglets after DON exposure. Moreover, Que pretreatment increased the cell viability and decreased the lactate dehydrogenase (LDH) activity (p < 0.05) in the supernatant of IPEC-1 cells after DON challenge. Que treatment also improved the epithelial barrier function indicated by a higher transepithelial electrical resistance (TEER) (p < 0.001), lower fluorescein isothiocyanate-labeled dextran (FD4) flux (p < 0.001), and better distribution of occludin and claudin-1 (p < 0.05) after DON challenge. Additionally, pretreatment with Que also inhibited the protein abundance of t-RIP1, p-RIP1, t-RIP3, p-RIP3, t-MLKL, and p-MLKL (p < 0.05) in IPEC-1 cells after DON challenge. In general, our data suggest that Que can ameliorate DON-induced intestinal injury and barrier dysfunction associated with suppressing the necroptosis signaling pathway.