Danfeng Zhang

Purpose: Recently, high-resolution magnetic resonance imaging (HR-MRI) has been used to depict the wall characteristics of the intracranial arteries. The aim of this study was to explain the relationship between the remodeling patterns and acute ischemic stroke in patients with atherosclerotic middle cerebral artery (MCA) stenosis using HR-MRI. Material and methods: From August 2015 to May 2016, we prospectively screened 33 consecutive patients with unilateral MCA stenosis using time-to-flight (TOF) MR angiography, including 15 patients with symptomatic MCA stenosis and 18 patients with asymptomatic MCA stenosis. Among them, 14 patients were diagnosed as positive remodeling (PR) and 19 as negative remodeling or non-remodeling. The cross-sectional images of the stenotic MCA wall on HR-MRI including T1WI, T2WI, and PDWI were compared between the symptomatic group and the asymptomatic group as well as the PR group and the non-PR group, based on the vessel area, lumen area, wall area, plaque area, degree of stenosis, remodeling index, and NIHSS score. Results: The symptomatic group had larger wall area (P=0.040), plaque area (P<0.001), degree of stenosis (P=0.038), remodeling index (P<0.001), and NIHSS score (P=0.003) as well as smaller lumen area (P=0.001) than the asymptomatic group. In addition, more PR patients were observed in symptomatic group. The PR group had larger plaque area (P=0.014) and NIHSS score (P=0.037) than the non-PR group. Demographic and clinical characteristics between the symptomatic group and the asymptomatic group, the PR group and the non-PR group showed no statistical difference. Conclusions: The current study suggests that the HR-MRI has emerged as a promising tool to detect the characteristics of intracranial arteries wall and reveal the relationship between remodeling patterns and ischemic stroke. The PR is an unsafe remodeling way and is prone to cause acute ischemic stroke.

In the present study, conditions for Bacillus mucilaginous fermentation using Agaricus bisporus wastewater as culture medium were optimized. We analyzed the total number of living B. mucilaginous in the fermentation broth using multispectral imaging flow cytometry. Single-factor experiments were carried out, where a Plackett–Burman design was used to screen out three factors from the original six factors of processing wastewater solubility, initial pH, inoculum size, liquid volume, culture temperature, and rotation speed that affected the total number of viable B. mucilaginous. The Box–Behnken response surface method was used to optimize interactions between the three main factors and predict optimal fermentation conditions. Factors significantly affecting the total number of viable B. mucilaginous, including shaking speed, culturing temperature, and initial pH, were investigated. The optimum conditions for B. mucilaginous fermentation in A. bisporus wastewater were a rotational speed of 195 rpm, culture temperature of 29 °C, initial pH of 6.5, solubility of 0.5%, 8% inoculation volume, and 90 mL liquid volume in a 250 mL flask, culture time of 48 h. Under these conditions, the concentration of total viable bacteria reached 2.16 ± 0.02 × 108 Obj/mL, which meets the national standard. A. bisporus wastewater can be used for the cultivation of B. mucilaginous.

Multiple myeloma (MM) is an aggressive malignancy characterized by terminally differentiated plasma cells accumulation in the bone marrow (BM). MM BM exhibits elevated MΦs (macrophages) numbers relative to healthy BM. Current evidence indicates that MM-MΦs (MM-associated macrophages) have pro-myeloma functions, and BM MM-MΦs numbers negatively correlate with patient survival. Here, we found that BMI1, a polycomb-group protein, modulates the pro-myeloma functions of MM-MΦs, which expressed higher BMI1 levels relative to normal MΦs. In the MM tumor microenvironment, hedgehog signaling in MΦs was activated by MM-derived sonic hedgehog, and BMI1 transcription subsequently activated by c-Myc. Relative to wild-type MM-MΦs, BMI1-KO (BMI1 knockout) MM-MΦs from BM cells of BMI1-KO mice exhibited reduced proliferation and suppressed expression of angiogenic factors. Additionally, BMI1-KO MM-MΦs lost their ability to protect MM cells from chemotherapy-induced cell death. In vivo analysis showed that relative to wild-type MM-MΦs, BMI1-KO MM-MΦs lost their pro-myeloma effects. Together, our data show that BMI1 mediates the pro-myeloma functions of MM-MΦs.

Our previous data showed that young female multiple myeloma (MM) patients had a low frequency of osteolytic lesions. Based on this clinical observation, we found that estrogen cell signaling played a regulatory role in MM bone disease (MMBD), and the estrogen-responsive gene microtubule-associated serine/threonine kinase family member 4 (MAST4) was a critical factor. The presence of estrogen in cell cultures promoted MAST4 expression in MM cells, while knocking down estrogen receptor 1 (ESR1) inhibited MAST4 expression. Chromatin immunoprecipitation assay suggested a binding site of ESR1 on the MAST4 promoter. Bisphosphonates, such as zoledronic acid (ZOL), which was widely used in MMBD control, could stimulate MAST4 expression in MM cells by promoting ESR1 expression. MAST4 interacted with phosphatase and tensin homolog (PTEN), therefore regulating the PI3K-Akt-mTOR pathway and the expression of downstream cytokines, such as CCL2/3/4. MAST4 knockdown (MAST4-KD) or ESR1 knockdown (ESR1-KD) MM cells had repressed PTEN activity, elevated PI3K-Akt-mTOR activity, and increased CCL2/3/4 expressions. Coculture of MAST4-KD or ESR1-KD MM cells with pre-osteoclasts (pre-OCs) stimulated OC formation in vitro, whereas neutralizing antibodies of CCL2/3/4 attenuated such stimulation. In mouse models, mice inoculated with MAST4-KD or ESR1-KD MM cells had severer MMBD than control knockdown (CTR-KD). The correlations between MAST4 and ESR1 expressions in MMBD, as well as related cell signaling pathways, were confirmed in analyses using gene expression profiles (GEPs) of patients' MM cells. The negative correlation of MAST4 expression and occurrence of MMBD was further validated by patients' immunohistochemical tissue array. Overall, our data suggested that estrogen cell signaling negatively regulated MMBD through MAST4. © 2022 American Society for Bone and Mineral Research (ASBMR).

Aim Previous studies have shown that the fibrinogen to albumin ratio (FAR) is closely related to the severity and prognosis of coronary atherosclerosis. In this study, we sought to evaluate the association between FAR and the degree of coronary artery calcification (CAC) in patients with chronic kidney disease (CKD). Methods In this retrospective study, 218 patients with CKD were stratified into low, medium and high FAR groups according to the tertiles of the FAR values. The CAC scores, clinical information and laboratory test results of the three FAR groups were compared. To explore the relationship between FAR and CAC we conducted binary logistic regression and correlation analyses. Results In the low FAR group, the CAC scores were significantly lower than those in the medium and high FAR groups ( P &lt; 0.001). There was a significant correlation between the FAR and CAC scores ( r = 0.510, P &lt; 0.001). The FAR was an independent predictor of CAC (OR = 1.106, 95% CI [1.004–1.218], P = 0.042). Conclusion In patients with CKD, the FAR can be considered as an effective predictor of CAC.