Theoretical Study of Am(III) and Eu(III) Separation by a Bipyridyl Phosphate Ligand.

Actinide An(III) and lanthanide Ln(III) are known to exhibit similar chemical properties; thus, it is difficult to distinguish them in the separation of highly radioactive waste liquids. One potential method to efficiently separate actinides and lanthanides involves the design and development of phosphorus-oxygen-bonded ligands with solvent extraction separation. Here, a bipyridine phosphate ligand with two isopropyl and phosphate groups is introduced to selectively extract actinides. The electronic structure, bonding properties, thermodynamic behavior, and quantum theory of atoms in molecules (QTAIM) of Am(III) and Eu(III) complexes with the bipyridine phosphate ligands were analyzed by using density functional theory (DFT) calculations. The analysis demonstrates that the Am-N bond exhibits stronger covalent characteristics than the Eu-N bond, indicating that the bipyridine phosphate ligand had better selectivity for Am(III) than for Eu(III) in terms of binding affinity. The thermodynamic analysis established the complex [ML(NO3)2(H2O)2]+ as the most stable species during the complexation process. The results indicate great potential for utilizing the bipyridine phosphate ligand for the effective separation of An(III)/Ln(III) in spent fuel reprocessing experiments.

[Application Progress of Shared Decision Making Model in Patients
with Thoracic Cancer].

As a new diagnosis and treatment decision-making model, shared decision making (SDM) can effectively solve the problem of patient compliance in the diagnosis and treatment of thoracic tumors, balance the status of both doctors and patients, and gradually get attention and application in the clinical practice of thoracic surgery. The application of SDM in the diagnosis and treatment of thoracic tumors is conducive to improve doctors' diagnosis and treatment level and alleviating the pressure of responsibility, reduce patients' psychological pressure and improve patients' compliance and also improve medical trust and reduce doctor-patient conflict. Due to the limited medical literacy and autonomy of patients, the time for diagnosis and treatment is short due to the imbalance of doctor-patient ratio. Meanwhile, due to the limited sample size of existing studies, SDM model cannot be proved to have a clear gain for the treatment of thoracic tumors, and the implementation of SDM model still faces resistance. In the future, the development of auxiliary decision-making system and the improvement of doctors' humanistic care ability will be conducive to promote the practical application of SDM model in thoracic surgery.
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TP53 in MDS and AML: Biological and clinical advances.

Recently, the WHO-5 and the ICC 2022 criteria have emphasized poor prognosis in AML/MDS patients with multi-hit TP53 mutations, whereas mutated TP53 plays a critical role in tumorigenesis, drawing substantial interest in exploring its biological behaviors. Diverse characteristics of TP53 mutations, including types, VAF, CNVs, allelic status, karyotypes, and concurrent mutations have been extensively studied. Novel potential targets and comprehensive treatment strategies nowadays are under swift development, owing to great advances in technology. However, accurately predicting prognosis of patients with TP53-mutated myeloid neoplasms remains challenging. And there is still a lack of effective treatment for those patients.

A review of traditional Chinese medicine diagnosis using machine learning: Inspection, auscultation-olfaction, inquiry, and palpation.

Traditional Chinese medicine (TCM) is an essential part of the Chinese medical system and is recognized by the World Health Organization as an important alternative medicine. As an important part of TCM, TCM diagnosis is a method to understand a patient's illness, analyze its state, and identify syndromes. In the long-term clinical diagnosis practice of TCM, four fundamental and effective diagnostic methods of inspection, auscultation-olfaction, inquiry, and palpation (IAOIP) have been formed. However, the diagnostic information in TCM is diverse, and the diagnostic process depends on doctors' experience, which is subject to a high-level subjectivity. At present, the research on the automated diagnosis of TCM based on machine learning is booming. Machine learning, which includes deep learning, is an essential part of artificial intelligence (AI), which provides new ideas for the objective and AI-related research of TCM. This paper aims to review and summarize the current research status of machine learning in TCM diagnosis. First, we review some key factors for the application of machine learning in TCM diagnosis, including data, data preprocessing, machine learning models, and evaluation metrics. Second, we review and summarize the research and applications of machine learning methods in TCM IAOIP and the synthesis of the four diagnostic methods. Finally, we discuss the challenges and research directions of using machine learning methods for TCM diagnosis.

Immunosuppressive role of BDNF in therapy-induced neuroendocrine prostate cancer.

Prostate stromal cells play a crucial role in the promotion of tumor growth and immune evasion in the tumor microenvironment (TME) through intricate molecular alterations in their interaction with prostate cancer (PCa) cells. While the impact of these cells on establishing an immunosuppressive response and influencing PCa aggressiveness remains incompletely understood. Our study shows that the activation of the leukemia inhibitory factor (LIF)/LIF receptor (LIFR) pathway in both prostate tumor and stromal cells, following androgen deprivation therapy (ADT), leads to the development of an immunosuppressive TME. Activation of LIF/LIFR signaling in PCa cells induces neuroendocrine differentiation (NED) and upregulates immune checkpoint expression. Inhibition of LIF/LIFR attenuates these effects, underscoring the crucial role of LIF/LIFR in linking NED to immunosuppression. Prostate stromal cells expressing LIFR contribute to NED and immunosuppressive marker abundance in PCa cells, while LIFR knockdown in prostate stromal cells reverses these effects. ADT-driven LIF/LIFR signaling induces brain-derived neurotrophic factor (BDNF) expression, which, in turn, promotes NED, aggressiveness, and immune evasion in PCa cells. Clinical analyses demonstrate elevated BDNF levels in metastatic castration-resistant PCa (CRPC) and a positive correlation with programmed death-ligand 1 (PDL1) and immunosuppressive signatures. This study shows that the crosstalk between PCa cells and prostate stromal cells enhances LIF/LIFR signaling, contributing to an immunosuppressive TME and NED in PCa cells through the upregulation of BDNF.

Structural characteristics of steamed Polygonatum cyrtonema polysaccharide and its bioactivity on colitis via improving the intestinal barrier and modifying the gut microbiota.

Steamed Polygonatum cyrtonema has been commonly used clinically for its gaining effect, whose main active ingredient is a polysaccharide. A water-soluble polysaccharide named PSP-W-1 was isolated from steamed Polygonatum cyrtonema. PSP-W-1 was characterized as a galactan having a backbone consisting predominately of 1,4-ß-linked Galp branched at the C-6 position by T-ß-linked Galp with a molecular weight of 14.4 kDa. PSP-W-1 could inhibit the overproduction of inflammatory factors and inflammatory mediators (iNOS, IL-6, COX-2) in dextran sodium sulfate-induced colitis mice. Oral administration of PSP-W-1 dramatically alleviated colonic pathological damage, repaired the intestinal barrier (occludin and ZO-1) and regulated the intestinal microbiota by increasing the abundance of norank_f_Muribaculaceae, Lactobacillus and norank_f_norank_o_Clostridia UCG-014, while decreasing the abundance of Bacteroides and Escherichia-Shigella to alleviate colitis symptoms. Overall, our findings suggest that PSP-W-1 might be a therapeutic option for both the prevention and treatment of colitis.

Applications of the Yariv reagent in polysaccharide analysis and plant physiology from theory to practice.

Arabinogalactan (AG), a biologically active substance found abundantly in plants, is of significant interest in plant physiology due to its unique physicochemical properties. Yariv reagent, widely utilized in AG-II related applications, forms insoluble precipitates when bound to AG-II. This paper provides a comprehensive overview of the synthesis methods, physicochemical properties, and various dissociation methods of the Yariv reagent to enhance its utility in AG-II studies. Furthermore, the review explores the binding mechanisms and applications of the Yariv reagent, highlighting the advancements in studying the Yariv-AG complex in plant physiology. The aim of this review is to inspire new research ideas and foster novel applications of the Yariv reagent from synthesis to implementation.

Cu(II) Coordination Polymers Containing Mixed Ligands with Different Flexibilities: Structural Diversity and Iodine Adsorption.

Reactions of N,N'-bis(3-methylpyridyl)oxalamide (L1), N,N'-bis(3-methylpyridyl)adipoamide (L2) and N,N'-bis(3-methylpyridyl)sebacoamide (L3) with tricarboxylic acids and Cu(II) salts afforded {[Cu(L1)(1,3,5-HBTC)]·H2O}n (1,3,5-H3BTC = 1,3,5-benzenetricarboxylic acid), 1, {[Cu1.5(L2)1.5(1,3,5-BTC)(H2O)2]·6.5H2O}n, 2, [Cu(L2)0.5(1,3,5-HBTB)]n (1,3,5-H3BTB = 1,3,5-tri(4-carboxyphenyl)benzene), 3, [Cu4(L3)(OH)2(1,3,5-BTC)2]n, 4, {[Cu3(L3)2(1,3,5-BTB)2]·2.5MeOH·2H2O}n, 5, and {[Cu3(L3)2(1,3,5-BTB)2 ]·DMF·2H2O}n, 6, which have been structurally characterized by using single crystal X-ray crystallography. Complexes 1-4 form a 2D layer with the {44.62}-sql topology, a 2D layer with the (4.62)2(42.62.82)-bex topology, a three-fold interpenetrated 3D net with the (412·63)-pcu topology and a 3D framework with the (410·632·83)(42·6)2(43·63) topology, respectively, whereas 5 and 6 are 3D frameworks with the (63)2(64·82)(68·85·102) topology. Complex 5 shows a better iodine adsorption factor of 290.0 mg g-1 at 60 °C for 360 min than the other ones, revealing that the flexibility of the spacer ligand governs the structural diversity and the adsorption capacity.

Macrophages modulate fibrosis during newt lens regeneration.

Background: Previous studies indicated that macrophages play a role during lens regeneration in newts, but their function has not been tested experimentally. Methods: Here we generated a transgenic newt reporter line in which macrophages can be visualized in vivo. Using this new tool, we analyzed the location of macrophages during lens regeneration. We uncovered early gene expression changes using bulk RNAseq in two newt species, Notophthalmus viridescens and Pleurodeles waltl. Next, we used clodronate liposomes to deplete macrophages, which inhibited lens regeneration in both newt species. Results: Macrophage depletion induced the formation of scar-like tissue, an increased and sustained inflammatory response, an early decrease in iris pigment epithelial cell (iPEC) proliferation and a late increase in apoptosis. Some of these phenotypes persisted for at least 100 days and could be rescued by exogenous FGF2. Re-injury alleviated the effects of macrophage depletion and re-started the regeneration process. Conclusions: Together, our findings highlight the importance of macrophages in facilitating a pro-regenerative environment in the newt eye, helping to resolve fibrosis, modulating the overall inflammatory landscape and maintaining the proper balance of early proliferation and late apoptosis.

Expression profiles of oviductal mRNAs and lncRNAs in the follicular phase and luteal phase of sheep (Ovis aries) with 2 fecundity gene (FecB) genotypes.

FecB (also known as BMPR1B) is a crucial gene in sheep reproduction, which has a mutation (A746G) that was found to increase the ovulation rate and litter size. The FecB mutation is associated with reproductive endocrinology, such mutation can control external estrous characteristics and affect follicle-stimulating hormone during the estrous cycle. Previous researches showed that the FecB mutation can regulate the transcriptomic profiles in the reproductive-related tissues including hypothalamus, pituitary, and ovary during the estrous cycle of small-tailed Han (STH) sheep. However, little research has been reported on the correlation between FecB mutation and the estrous cycle in STH sheep oviduct. To investigate the coding and noncoding transcriptomic profiles involved in the estrous cycle and FecB in the sheep oviduct, RNA sequencing was performed to analyze the transcriptomic profiles of mRNAs and long noncoding RNAs (lncRNAs) in the oviduct during the estrous cycle of STH sheep with mutant (FecBBB) and wild-type (FecB++) genotypes. In total, 21,863 lncRNAs and 43,674 mRNAs were screened, the results showed that mRNAs had significantly higher expression levels than the lncRNAs, and the expression levels of these screened transcripts were lower in the follicular phase than they were in the luteal phase. Among them, the oviductal glycoprotein gene (OVGP1) had the highest expression level. In the comparison between the follicular and luteal phases, 57 differentially expressed (DE) lncRNAs and 637 DE mRNAs were detected, including FSTL5 mRNA and LNC_016628 lncRNA. In the comparison between the FecBBB and FecB++ genotypes, 26 DE lncRNAs and 421 DE mRNAs were detected, including EEF1D mRNA and LNC_006270 lncRNA. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis indicated that the DE mRNAs were enriched mainly in terms related to reproduction such as the tight junction, SAGA complex, ATP-binding cassette, nestin, and Hippo signaling pathway. The interaction network between DE lncRNAs and DE mRNAs indicated that LNC_018420 may be the key regulator in sheep oviduct. Together, our results can provide novel insights into the oviductal transcriptomic function against a FecB mutation background in sheep reproduction.

OCTSharp: an open-source and real-time OCT imaging software based on C.

Optical coherence tomography (OCT) demands massive data processing and real-time displaying during high-speed imaging. Current OCT imaging software is predominantly based on C++, aiming to maximize performance through low-level hardware management. However, the steep learning curve of C++ hinders agile prototyping, particularly for research purposes. Moreover, manual memory management poses challenges for novice developers and may lead to potential security issues. To address these limitations, OCTSharp is developed as an open-source OCT software based on the memory-safe language C#. Within the managed C# environment, OCTSharp offers synchronized hardware control, minimal memory management, and GPU-based parallel processing. The software has been thoroughly tested and proven capable of supporting real-time image acquisition, processing, and visualization with spectral-domain OCT systems equipped with the latest advanced hardware. With these enhancements, OCTSharp is positioned to serve as an open-source platform tailored for various applications.

Association between DNA Methylation in the Core Promoter Region of the CUT-like Homeobox 1 (CUX1) Gene and Lambskin Pattern in Hu Sheep.

CUT-like homeobox 1 (CUX1) has been proven to be a key regulator in sheep hair follicle development. In our previous study, CUX1 was identified as a differential expressed gene between Hu sheep lambskin with small wave patterns (SM) and straight wool patterns (ST); however, the exact molecular mechanism of CUX1 expression has been obscure. As DNA methylation can regulate the gene expression, the potential association between CUX1 core promotor region methylation and lambskin pattern in Hu sheep was explored in the present study. The results show that the core promoter region of CUX1 was present at (-1601-(-1) bp) upstream of the transcription start site. A repressive region (-1151-(-751) bp) was also detected, which had a strong inhibitory effect on CUX1 promoter activity. Bisulfite amplicon sequencing revealed that no significant difference was detected between the methylation levels of CUX1 core promoter region in SM tissues and ST tissues. Although the data demonstrated the differential expression of CUX1 between SM and ST probably has no association with DNA methylation, the identification of the core region and a potential repressive region of CUX1 promoter can enrich the role of CUX1 in Hu sheep hair follicle development.

NCAPG Regulates Myogenesis in Sheep, and SNPs Located in Its Putative Promoter Region Are Associated with Growth and Development Traits.

Previously, NCAPG was identified as a candidate gene associated with sheep growth traits. This study aimed to investigate the direct role of NCAPG in regulating myogenesis in embryonic myoblast cells and to investigate the association between single-nucleotide polymorphisms (SNPs) in its promoter region and sheep growth traits. The function of NCAPG in myoblast proliferation and differentiation was detected after small interfering RNAs (siRNAs) knocked down the expression of NCAPG. Cell proliferation was detected using CCK-8 assay, EdU proliferation assay, and flow cytometry cell cycle analysis. Cell differentiation was detected via cell immunofluorescence and the quantification of myogenic regulatory factors (MRFs). SNPs in the promoter region were detected using Sanger sequencing and genotyped using the improved multiplex ligation detection reaction (iMLDR®) technique. As a result, a notable decrease (p < 0.01) in the percentage of EdU-positive cells in the siRNA-694-treated group was observed. A significant decrease (p < 0.01) in cell viability after treatment with siRNA-694 for 48 h and 72 h was detected using the CCK-8 method. The quantity of S-phase cells in the siRNA-694 treatment group was significantly decreased (p < 0.01). After interfering with NCAPG in myoblasts during induced differentiation, the relative expression levels of MRFs were markedly (p < 0.05 or p < 0.01) reduced compared with the control group on days 5-7. The myoblast differentiation in the siRNA-694 treatment group was obviously suppressed compared with the control group. SNP1, SNP2, SNP3, and SNP4 were significantly (p < 0.05) associated with all traits except body weight measured at birth and one month of age. SNP5 was significantly (p < 0.05) associated with body weight, body height, and body length in six-month-old sheep. In conclusion, interfering with NCAPG can inhibit the proliferation and differentiation of ovine embryonic myoblasts. SNPs in its promoter region can serve as potential useful markers for selecting sheep growth traits.

New Fusarin Derivatives from the Marine Algicolous Fungus Penicillium steckii SCSIO41040.

Five new fusarin derivatives, steckfusarins A-E (1-5), and two known natural products (6, 7), were isolated and identified from the marine algicolous fungus Penicillium steckii SCSIO 41040. The new compounds, including absolute configurations, were determined by spectroscopic analyses and calculated electronic circular dichroism (ECD). All new compounds were evaluated for their antioxidant, antibacterial, antifungal, antiviral, cytotoxic, anti-inflammatory, antioxidant, cholesterol-lowering, acetyl cholinesterase (AChE) enzyme and 6-phosphofructo-2-kinase (PFKFB3) and phosphatidylinositol-3-kinase (PI3K) inhibitory activities. The biological evaluation results revealed that compound 1 exhibited radical scavenging activity against 2,2-diphenyl-1-picrylhydrazylhydrate (DPPH), with an IC50 value of 74.5 µg/mL. In addition, compound 1 also showed weak anti-inflammatory activity at a concentration of 20 µM.

Association between triglyceride glucose index and severity of diabetic foot ulcers in type 2 diabetes mellitus.

BACKGROUND: Triglyceride glucose (TyG) index is a good surrogate biomarker to evaluate insulin resistance (IR). The study aimed to investigate whether the TyG index is related to the severity of diabetic foot ulcers (DFUs) in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 1059 T2DM patients were enrolled in this observational, retrospective, single-center study. TyG index was calculated as ln[fasting triglycerides (mg/dl) × fasting glucose (mg/ dl)/2]. The severity of DFUs was classified into mild-to-moderate DFUs (Wagner grade score < 3) and severe DFUs (Wagner grade score ≥ 3) based on Wagner classification. Patients were stratified according to the tertiles of TyG index. Logistic regression models were implemented to explore the association between TyG index and the severity of DFUs. Subgroup analyses were used to verify the reliability of results. RESULTS: Compared with the reference lowest TyG tertile (T1), the highest tertile (T3) was associated with 0.377-fold increased risk of prevalence of severe DFUs (odds ratio [OR] 1.377, 95% confidence interval [CI] 1.017-1.865) (P = 0.039). After adjusting for potential confounders, the multivariable-adjusted OR and 95% CI were 1.506 (1.079-2.103) (P = 0.016) in patients with highest tertile. Moreover, subgroup analyses indicated that the association was stronger among men, patients with age ≥ 65 years, duration of diabetes more than 10 years, or without PAD. CONCLUSIONS: Elevated TyG index is independently associated with severity of DFUs even after adjusting conventional confounders.

Macrophages modulate fibrosis during newt lens regeneration.

Previous studies indicated that macrophages play a role during lens regeneration in newts, but their function has not been tested experimentally. Here we generated a transgenic newt reporter line in which macrophages can be visualized in vivo. Using this new tool, we analyzed the location of macrophages during lens regeneration. We uncovered early gene expression changes using bulk RNAseq in two newt species, Notophthalmus viridescens and Pleurodeles waltl. Next, we used clodronate liposomes to deplete macrophages, which inhibited lens regeneration in both newt species. Macrophage depletion induced the formation of scar-like tissue, an increased and sustained inflammatory response, an early decrease in iris pigment epithelial cell (iPEC) proliferation and a late increase in apoptosis. Some of these phenotypes persisted for at least 100 days and could be rescued by exogenous FGF2. Re-injury alleviated the effects of macrophage depletion and re-started the regeneration process. Together, our findings highlight the importance of macrophages in facilitating a pro-regenerative environment in the newt eye, helping to resolve fibrosis, modulating the overall inflammatory landscape and maintaining the proper balance of early proliferation and late apoptosis.

CHRM4/AKT/MYCN upregulates interferon alpha-17 in the tumor microenvironment to promote neuroendocrine differentiation of prostate cancer.

Current treatment options for prostate cancer focus on targeting androgen receptor (AR) signaling. Inhibiting effects of AR may activate neuroendocrine differentiation and lineage plasticity pathways, thereby promoting the development of neuroendocrine prostate cancer (NEPC). Understanding the regulatory mechanisms of AR has important clinical implications for this most aggressive type of prostate cancer. Here, we demonstrated the tumor-suppressive role of the AR and found that activated AR could directly bind to the regulatory sequence of muscarinic acetylcholine receptor 4 (CHRM4) and downregulate its expression. CHRM4 was highly expressed in prostate cancer cells after androgen-deprivation therapy (ADT). CHRM4 overexpression may drive neuroendocrine differentiation of prostate cancer cells and is associated with immunosuppressive cytokine responses in the tumor microenvironment (TME) of prostate cancer. Mechanistically, CHRM4-driven AKT/MYCN signaling upregulated the interferon alpha 17 (IFNA17) cytokine in the prostate cancer TME after ADT. IFNA17 mediates a feedback mechanism in the TME by activating the CHRM4/AKT/MYCN signaling-driven immune checkpoint pathway and neuroendocrine differentiation of prostate cancer cells. We explored the therapeutic efficacy of targeting CHRM4 as a potential treatment for NEPC and evaluated IFNA17 secretion in the TME as a possible predictive prognostic biomarker for NEPC.

New Meroterpenoids and Anti-Osteoclastogenic Polyketides from the Mangrove-Derived fungus Arthrinium sp. SCSIO 41306.

Two new meroterpenoids, arthrinones A and B (1 and 2), along with six known compounds (3-8), were obtained from the fungus Arthrinium sp. SCSIO 41306. Comprehensive methods such as chiral-phase HPLC analysis and ECD calculations were applied to determine the absolute configurations. Griseofulvin (5), kojic acid (6), and 1H-indole-3-carboxaldehyde (8) showed inhibition of NF-κB in RAW 264.7 macrophages induced by lipopolysaccharide (LPS) with IC50 values of 22.21, 13.87 and 19.31 µM, respectively. In addition, griseofulvin (5) inhibited receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation in a dose-dependent manner without visible evidence of cytotoxicity in bone marrow macrophages (BMMs). This is the first report on the activity of griseofulvin (5) to inhibit osteoclast formation (IC50 10.09±0.21 µM).