Bimetallic Gold/Silver and Bioactive Camptothecin Hybrid Nanoparticles for Eradication of Cancer Stem Cells in a Combination Manner.

The defeat of cancer is still a challenge due to the existence of cancer stem cells (CSCs) because they resist conventional chemotherapy via multifactor regulated mechanisms. Consequently, one-dimensional action toward CSCs cannot work. Herein, we used rationally designed hybrid nanoparticles as a combined cancer therapy, hoping to form a multidimensional control network. In this paper, gold/silver alloy nanoparticle decorated camptothecin nanocrystals were formulated according to complementary anti-CSC mechanisms from gold, silver, and organic drug. This smart drug formulation could combine chemotherapy and thermotherapy, target different tumor sites, and demonstrate versatile toxicity profiles from each component. Major results indicated that this nanosystem demonstrated indiscriminately effective cytotoxic/proapoptotic/necrotic activity against bulk MCF-7 cells and their CSC subpopulation, in particular under laser ablation. Moreover, this nanosystem displayed enhanced antineoplastic activity against CSC spheroids, resulting in a significant reduction in their number and size, that is, their self-renewal capacity. All the results indicated that CSCs upon treatment of these new hybrid nanoparticles underwent reduced stemness and conversion from the original quiescent state and recovered their sensitivity toward chemotherapy. The relevant anticancer mechanism was ascribed to NIR-pH dual responsive drug release, synergistic/combined thermo-chemotherapy of organic drug and inorganic alloy nanoparticles, enhanced cellular uptake mediated by alloy nanoparticles, and Ag+-induced biomembrane damage. This thermo-chemotherapy platform provides a new combinatorial strategy for inorganic and organic agents in the complete elimination of CSCs.

Evaluating the impact of soil erosion on soil quality in an agricultural land, northeastern China.

The impact of soil erosion on soil quality is still not systematically understood. The purpose of this study was thus to quantify the impact of soil erosion on soil quality and its change with slope morphology in an agricultural field, northeastern China based on radionuclide 137Cs, unmanned aerial vehicle derived high resolution digital elevation model, and soil sampling. 137Cs method yielded an average soil erosion rate of - 275 t km-2 yr-1 ranging from - 1870 to 1557 t km-2 yr-1. The soil quality index derived from total dataset (SQI_TDS) can be well explained by that derived from minimum data set (SQI_MDS) with a determination coefficient R2 of 0.874. SOM, sand, and cation exchange capacity in the MDS play more important roles than other soil indicators. Soil quality was significantly affected by soil erosion, with Adj. R2 of 0.29 and 0.33 for SQI_TDS and SQI_MDS, respectively. The spatial variations of soil erosion and soil quality were both affected by slope topography. Soil erosion must be controlled according to topographic and erosion characteristics in northeastern China.

A Green Synthesis of Au-Ag Alloy Nanoparticles using Polydopamine Chemistry: Evaluation of their Anticancer Potency Towards Both MCF-7 Cells and their Cancer Stem Cells Subgroup.

BACKGROUND: Limited chemotherapy efficacy and cancer stem cells (CSCs)-induced therapeutic resistance are major difficulties for tumour treatment. Adopting more efficient therapies to eliminate bulk-sensitive cancer cells and resistant CSCs is urgently needed. METHODS: Based on the potential and functional complementarity of gold and silver nanoparticles (AuNPs or AgNPs) on tumour treatment, bimetallic NPs (alloy) have been synthesized to obtain improved or even newly emerging bioactivity from a combination effect. This study reported a facile, green and economical preparation of Au-Ag alloy NPs using biocompatible polydopamine (PDA) as a reductant, capping, stabilizing and hydrophilic agent. RESULTS: These alloy NPs were quasi-spherical with rough surfaces and recorded in diameters of 80 nm. In addition, these alloy NPs showed good water dispersity, stability and photothermal effect. Compared with monometallic counterparts, these alloy NPs demonstrated a dramatically enhanced cytotoxic/pro-apoptotic/necrotic effect towards bulk-sensitive MCF-7 and MDA-MB-231 cells. The underlying mechanism regarding the apoptotic action was associated with a mitochondria-mediated pathway, as evidenced by Au3+/Ag+ mediated Mitochondria damage, ROS generation, DNA fragmentation and upregulation of certain apoptotic-related genes (Bax, P53 and Caspase 3). Attractively, these Au-Ag alloy NPs showed a remarkably improved inhibitory effect on the mammosphere formation capacity of MCF-7 CSCs. CONCLUSION: All the positive results were attributed to incorporated properties from Au, Ag and PDA, the combination effect of chemotherapy and photothermal therapy and the nano-scaled structure of Au-Ag alloy NPs. In addition, the high biocompatibility of Au-Ag alloy NPs supported them as a good candidate in cancer therapy.

Differences of serum glucose and lipid metabolism and immune parameters and blood metabolomics regarding the transition cows in the antepartum and postpartum period.

This study aims to investigate differences in metabolism regarding the transition cows. Eight cows were selected for the test. Serum was collected on antepartum days 14th (ap14) and 7th (ap7) and postpartum days 1st (pp1), 7th (pp7), and 14th (pp14) to detect biochemical parameters. The experiment screened out differential metabolites in the antepartum (ap) and postpartum (pp) periods and combined with metabolic pathway analysis to study the relationship and role between metabolites and metabolic abnormalities. Results: (1) The glucose (Glu) levels in ap7 were significantly higher than the other groups (p < 0.01). The insulin (Ins) levels of ap7 were significantly higher than pp7 (p = 0.028) and pp14 (p < 0.01), and pp1 was also significantly higher than pp14 (p = 0.016). The insulin resistance (HOMA-IR) levels of ap7 were significantly higher than ap14, pp7, and pp14 (p < 0.01). The cholestenone (CHO) levels of ap14 and pp14 were significantly higher than pp1 (p < 0.01). The CHO levels of pp14 were significantly higher than pp7 (p < 0.01). The high density lipoprotein cholesterol (DHDL) levels of pp1 were significantly lower than ap14 (p = 0.04), pp7 (p < 0.01), and pp14 (p < 0.01), and pp14 was also significantly higher than ap14 and ap7 (p < 0.01). (2) The interferon-gamma (IFN-γ) and tumor necrosis factor α (TNF-α) levels of ap7 were significantly higher than pp1 and pp7 (p < 0.01); the immunoglobulin A (IgA) levels of pp1 were significantly higher than ap7 and pp7 (p < 0.01); the interleukin-4 (IL-4) levels of pp7 were significantly higher than ap7 and pp1 (p < 0.01), the interleukin-6 (IL-6) levels of ap7 and pp1 were significantly higher than pp7 (p < 0.01). (3) Metabolomics identified differential metabolites mainly involved in metabolic pathways, such as tryptophan metabolism, alpha-linolenic acid metabolism, tyrosine metabolism, and lysine degradation. The main relevant metabolism was concentrated in lipid and lipid-like molecules, organic heterocyclic compounds, organic acids, and their derivatives. The results displayed the metabolic changes in the transition period, which laid a foundation for further exploring the mechanism of metabolic abnormalities in dairy cows in the transition period.

Vascular architecture characters and risk factors analysis of unstable moyamoya disease.

Background: In some MMD patients, the digital subtraction angiography (DSA) examination found, occlusion in the ipsilateral internal carotid artery or middle cerebral artery, accompanied by the formation of numerous moyamoya vessels. Conversely, the contralateral internal carotid artery or middle cerebral artery shows signs of stenosis without the presence of moyamoya vessels. Notably, cerebral perfusion studies reveal a similar or even more severe reduction in perfusion on the occluded side compared to the stenotic side. Importantly, clinical symptoms in these patients are typically attributed to ischemia caused by the stenotic side. This condition is referred to as unstable moyamoya disease (uMMD). Objective: This clinical research focuses on evaluating risk factors related to MMD and developing strategies to minimize postoperative complications. The study aims to analyze vascular characteristics and identify potential risk factors in patients with uMMD. Methods: The authors reviewed consecutive cases with complete clinical and radiological documentation of patients who underwent surgery between January 2018 and June 2023. Univariate analysis and multivariate logistic regression analysis were employed to understand the risk factors and prognosis of postoperative complications in uMMD. Results: Postoperative complications were retrospectively analyzed in 1481 patients (aged 14 to 65). Among them, 1,429 patients were assigned to the conventional treatment group, while 52 were in the unstable moyamoya disease group. The uMMD treatment group showed a significantly higher incidence of early postoperative complications such as RIND, cerebral infarction, and cerebral hemorrhage (p < 0.05). Univariate and multivariate logistic regression analyses were conducted on the postoperative complications of 52 uMMD patients. Initial symptoms of stenosis ≤50% (univariate: p = 0.008, multivariate: p = 0.015; OR [95% CI] =23.149 [1.853-289.217]) and choosing occluded side surgery (univariate: p = 0.043, multivariate: p = 0.018; OR [95% CI] =0.059 [0.006-0.617]) were identified as significant risk factors for postoperative neurological complications. Conclusion: Compared to the conventional treatment group, uMMD has higher complication rates, with vascular stenosis degree and surgical side selection identified as significant risk factors. A comprehensive understanding of preoperative clinical symptoms and vascular characteristics in moyamoya disease patients, coupled with the formulation of rational surgical plans, contributes positively to decreasing postoperative mortality and disability rates in uMMD.

MUP1 mediates urolithin A alleviation of chronic alcohol-related liver disease via gut-microbiota-liver axis.

Alcohol-related liver disease (ALD) is recognized as a global health crisis, contributing to approximately 20% of liver cancer-associated fatalities. Dysbiosis of the gut microbiome is associated with the development of ALD, with the gut microbial metabolite urolithin A (UA) exhibiting a potential for alleviating liver symptoms. However, the protective efficacy of UA against ALD and its underlying mechanism mediated by microbiota remain elusive. In this study, we provide evidence demonstrating that UA effectively ameliorates alcohol-induced metabolic disorders and hepatic endoplasmic reticulum (ER) stress through a specific gut-microbiota-liver axis mediated by major urinary protein 1 (MUP1). Moreover, UA exhibited the potential to restore alcohol-induced dysbiosis of the intestinal microbiota by enriching the abundance of Bacteroides sartorii (B. sartorii), Parabacteroides distasonis (P. distasonis), and Akkermansia muciniphila (A. muciniphila), along with their derived metabolite propionic acid. Partial attenuation of the hepatoprotective effects exerted by UA was observed upon depletion of gut microbiota using antibiotics. Subsequently, a fecal microbiota transplantation (FMT) experiment was conducted to evaluate the microbiota-dependent effects of UA in ALD. FMT derived from mice treated with UA exhibited comparable efficacy to direct UA treatment, as it effectively attenuated ER stress through modulation of MUP1. It was noteworthy that strong associations were observed among the hepatic MUP1, gut microbiome, and metabolome profiles affected by UA. Intriguingly, oral administration of UA-enriched B. sartorii, P. distasonis, and A. muciniphila can enhance propionic acid production to effectively suppress ER stress via MUP1, mimicking UA treatment. Collectively, these findings elucidate the causal mechanism that UA alleviated ALD through the gut-microbiota-liver axis. This unique mechanism sheds light on developing novel microbiome-targeted therapeutic strategies against ALD.