KCTD5 regulates Ikaros degradation induced by chemotherapeutic drug etoposide in hematological cells.

Therapy-related leukemia carries a poor prognosis, and leukemia after chemotherapy is a growing risk in clinic, whose mechanism is still not well understood. Ikaros transcription factor is an important regulator in hematopoietic cells development and differentiation. In the absence of Ikaros, lymphoid cell differentiation is blocked at an extremely early stage, and myeloid cell differentiation is also significantly affected. In this work, we showed that chemotherapeutic drug etoposide reduced the protein levels of several isoforms of Ikaros including IK1, IK2 and IK4, but not IK6 or IK7, by accelerating protein degradation, in leukemic cells. To investigate the molecular mechanism of Ikaros degradation induced by etoposide, immunoprecipitation coupled with LC-MS/MS analysis was conducted to identify changes in protein interaction with Ikaros before and after etoposide treatment, which uncovered KCTD5 protein. Our further study demonstrates that KCTD5 is the key stabilizing factor of Ikaros and chemotherapeutic drug etoposide induces Ikaros protein degradation through decreasing the interaction of Ikaros with KCTD5. These results suggest that etoposide may induce leukemic transformation by downregulating Ikaros via KCTD5, and our work may provide insights to attenuate the negative impact of chemotherapy on hematopoiesis.

Layered Chalcogenide Scintillators Enabled by Reversible Hydrous-Induced Phase Transformation for High-Resolution X-ray Imaging.

Scintillation materials have been widely used in various fields, such as medical diagnosis and industrial detection. Chalcogenides have the potential to become a new generation of high-performance scintillation materials due to their high effective atomic number and good resistance to radiation damage. However, research on their application in radiation detection is currently very scarce. Herein, single crystals of rare earth ion-doped ternary chalcogenides NaGaS2/Eu were grown by a high-temperature solid-phase method. It exhibits unique characteristics of structure transformation by absorbing water molecules from the air. To maintain the anhydrous phase of the material, we have used a strategy of organic-inorganic composites of epoxy resin and NaGaS2/Eu to prepare devices for radiation detection and discuss the irradiation luminescence properties of the two phases. The anhydrous phase of NaGaS2/Eu demonstrates excellent sensitivity to X-rays, with a low detection limit of 250 nGy s-1, which is approximately 1/22 of the medical imaging dose. Additionally, composite flexible films were prepared, which exhibited excellent performance in X-ray imaging. These films enable clear observation of a wide range of objects with a high spatial resolution of up to 13.2 line pairs per millimeter (lp mm-1), indicating that chalcogenide holds promising prospects in the realm of X-ray imaging applications.

Causal Relationship Between Circulating Immune Cells and Recurrent Spontaneous Abortion: A Bidirectional Mendelian Randomization Study.

BACKGROUND: Recurrent spontaneous abortion (RSA) is a serious and common complication of pregnancy caused by multiple factors. The etiology remains incompletely understood, but immunologic factors play important roles. Here, we aimed to evaluate whether circulating immune cells causally impacted RSA. METHODS: In this study, we conducted a comprehensive two-sample Mendelian randomization (MR) study to determine the causal association between the 731 immunophenotypes of human peripheral blood lymphocytes and the number of spontaneous abortions as well as recurrent miscarriage. Sensitivity analyses were performed to assess and minimize heterogeneity and horizontal pleiotropy. Reverse MR analysis was used to assess reverse causality. RESULTS: After Bonferroni-correction, eight immunophenotypes were significantly associated with the number of spontaneous abortions: FSC-A on CD4+ T cell (beta = -0.051, 95% CI = [-0.085, -0.017], P-value = 0.004), CD8 on HLA DR+ CD8+ T cell (beta = -0.040, 95% CI = [-0.067, -0.014], P-value = 0.003), HLA DR on CD33dim HLA DR+ CD11b- (beta = -0.021, 95% CI = [-0.036, -0.005], P-value = 0.010), HLA DR+ T cell Absolute Count (beta = 0.022, 95% CI = [0.006, 0.037], P-value = 0.008), HLA DR+ T cell % lymphocyte (beta = 0.026, 95% CI = [0.010, 0.041], P-value = 0.001), HLA DR+ T cell % T cell (beta = 0.023, 95% CI = [0.007, 0.039], P-value = 0.004), HLA DR+ CD4+ T cell % lymphocyte (beta = 0.034, 95% CI = [0.007, 0.060], P-value = 0.012), and HLA DR on B cell (beta = 0.012, 95% CI = [0.003, 0.021], P-value = 0.010). In addition, we identified two immunophenotypes associated with recurrent miscarriage: HLA DR on B cell (OR = 0.854, 95% CI = [0.757, 0.964], P-value = 0.011), and CD19 on naive-mature B cell (OR = 4.595, 95% CI = [1.674, 12.617], P-value = 0.003). There was no evidence of heterogeneity, horizontal pleiotropy and reverse causality. CONCLUSIONS: Our study demonstrated a tight link between adaptive immune cells and RSA through genetic means, thus providing potential therapeutic targets or novel diagnostic biomarkers.

Cytochrome P450 CYP736A12 is crucial for Trichoderma asperellum-induced alleviation of phoxim phytotoxicity and reduction of pesticide residue in tomato roots.

Trichoderma can enhance the metabolism of organophosphate pesticides in plants, but the mechanism is unclear. Here, we performed high-throughput transcriptome sequencing of roots upon Trichoderma asperellum (TM) inoculation and phoxim (P) application in tomato (Solanum lycopersicum L.). A total of 4059 differentially expressed genes (DEGs) were obtained, including 2110 up-regulated and 1949 down-regulated DEGs in P vs TM+P. COG and KOG analysis indicated that DEGs were mainly enriched in signal transduction mechanisms. We then focused on the pesticide detoxification pathway and screened out cytochrome P450 CYP736A12 as a putative gene for functional analysis. We suppressed the expression of CYP736A12 in tomato plants by virus-induced gene silencing and analyzed tissue-specific phoxim residues, oxidative stress markers, glutathione pool, GST activity and related gene expression. Silencing CYP736A12 significantly increased phoxim residue and induced oxidative stress in tomato plants, by attenuating the TM-induced increased activity of antioxidant and detoxification enzymes, redox homeostasis and transcripts of detoxification genes including CYP724B2, GSH1, GSH2, GR, GPX, GST1, GST2, GST3, and ABC. The study revealed a critical mechanism by which TM promotes the metabolism of phoxim in tomato roots, which can be useful for further understanding the Trichoderma-induced xenobiotic detoxification and improving food safety.

A self-assembling bioactive oligopeptide hydrogel for the treatment of edema following prepuce surgery.

Edema of the prepuce is a common clinical complication following circumcision in urology. Nevertheless, the principal method of gauze wrapping in clinical practice has not yet been demonstrated to be an effective solution to the problem of postoperative edema. It is therefore evident that the development of functional dressings for the treatment of post-circumcision edema has considerable potential for both clinical application and translational significance. The objective of this study was to develop a single-component bioactive oligopeptide hydrogel dressing with favorable anti-inflammatory, pro-angiogenesis properties and biosafety for the treatment of edema following prepuce surgery. A hexapeptide (Ac-FFFGHK-OH) hydrogelator was designed and synthesized through the N-terminal modification of a human-derived glycine-histidine-lysine tripeptide (GHK) with an N-acetylated phenylalanine tripeptide (Ac-FFF). The bioactive Ac-FFFGHK-OH hydrogel can be prepared through a facile self-assembly method. Furthermore, a novel experimental animal model of post-circumcision edema in Sprague-Dawley rats was constructed and the in vivo anti-edema effect of the Ac-FFFGHK-OH hydrogel was confirmed. The mechanism of action in relieving edema was also investigated by in vitro cell experiments. This work may inspire alternative thinking for the development of mono-component bioactive oligopeptide hydrogels for the treatment of edema in various diseases.