Cocaine- and amphetamine-regulated transcript promotes the differentiation of mouse bone marrow-derived mesenchymal stem cells into neural cells

<p>Abstract</p> <p>Background</p> <p>Neural tissue has limited potential to self-renew after neurological damage. Cell therapy using BM-MSCs (bone marrow mesenchymal stromal cells) seems like a promising approach for the treatment of neurological diseases. However, the neural differentiation of stem cells influenced by massive factors and interactions is not well studied at present.</p> <p>Results</p> <p>In this work, we isolated and identified MSCs from mouse bone marrow. Co-cultured with CART (0.4 nM) for six days, BM-MSCs were differentiated into neuron-like cells by the observation of optical microscopy. Immunofluorescence demonstrated that the differentiated BM-MSCs expressed neural specific markers including MAP-2, Nestin, NeuN and GFAP. In addition, NeuN positive cells could co-localize with TH or ChAT by double-labled immunofluorescence and Nissl bodies were found in several differentiated cells by Nissl stain. Furthermore, BDNF and NGF were increased by CART using RT-PCR.</p> <p>Conclusion</p> <p>This study demonstrated that CART could promote the differentiation of BM-MSCs into neural cells through increasing neurofactors, including BNDF and NGF. Combined application of CART and BM-MSCs may be a promising cell-based therapy for neurological diseases.</p

Using Ipomoea aquatic as an environmental-friendly alternative to Elodea nuttallii for the aquaculture of Chinese mitten crab

Elodea nuttallii is widely used in Chinese mitten crab (CMC) rearing practice, but it is not a native aquatic plant and cannot endure high temperature. Thus, large E. nuttallii mortality and water deterioration events could occur during high-temperature seasons. The aim of this study was to identify the use of local macrophytes in CMC rearing practice, including Ipomoea aquatic and Oryza sativa. A completely randomized field experiment was conducted to investigate the crab yield, water quality, bacterioplankton community and functions in the three different systems (E. nuttallii, I. aquatic, and O. sativa). Average crab yields in the different macrophyte systems did not differ significantly. The I. aquatic and O. sativa systems significantly decreased the total nitrogen and nitrate-N quantities in the outflow waters during the rearing period compared to the E. nuttallii system, and the I. aquatic and O. sativa plants assimilated more nitrogen than the E. nuttallii plant. Moreover, the significant changes of bacterioplankton abundances and biodiversity in the three systems implied that cleanliness of rearing waters was concomitantly attributed to the differential microbial community and functions. In addition, principle component analysis successfully differentiated the bacterioplankton communities of the three macrophytes systems. Environmental factor fitting and the co-occurrence network analyses indicated that pH was the driver of bacterioplankton community structure. Functional predictions using PICRUSt (v.1.1.3) software based on evolutionary modeling indicated a higher potential for microbial denitrification in the I. aquatic and O. sativa systems. Notably, the O. sativa plants stopped growing in the middle of the rearing period. Thus, the I. aquatic system rather than the O. sativa system could be a feasible and environmental-friendly alternative to the E. nuttallii system in CMC rearing practice

Circulating tumor DNA clearance predicts prognosis across treatment regimen in a large real-world longitudinally monitored advanced non-small cell lung cancer cohort

Background: Although growth advantage of certain clones would ultimately translate into a clinically visible disease progression, radiological imaging does not reflect clonal evolution at molecular level. Circulating tumor DNA (ctDNA), validated as a tool for mutation detection in lung cancer, could reflect dynamic molecular changes. We evaluated the utility of ctDNA as a predictive and a prognostic marker in disease monitoring of advanced non-small cell lung cancer (NSCLC) patients.Methods: This is a multicenter prospective cohort study. We performed capture-based ultra-deep sequencing on longitudinal plasma samples utilizing a panel consisting of 168 NSCLC-related genes on 949 advanced NSCLC patients with driver mutations to monitor treatment responses and disease progression. The correlations between ctDNA and progression-free survival (PFS)/overall survival (OS) were performed on 248 patients undergoing various treatments with the minimum of 2 ctDNA tests.Results: The results of this study revealed that higher ctDNA abundance (P=0.012) and mutation count (P=8.5x10(-4)) at baseline are associated with shorter OS. We also found that patients with ctDNA clearance, not just driver mutation clearance, at any point during the course of treatment were associated with longer PFS (P=2.2x10(-1)6, HR 0.28) and OS (P=4.5x10(-6), HR 0.19) regardless of type of treatment and evaluation schedule.Conclusions: This prospective real-world study shows that ctDNA clearance during treatment may serve as predictive and prognostic marker across a wide spectrum of treatment regimens

Knockdown of PLAC1 inhibits BCa growth and migration through upregulation of FOXO3a

Placenta-specific protein 1 (PLAC1) is considered to play a pivotal role in cancer progression. Here, we investigated the role of PLAC1 in the growth and motility of bladder cancer (BCa) cells. Database analysis and Immunoblot assays were conducted to determine PLAC1 expression in BCa tissues and its correlation with patient prognosis. Furthermore, wound healing, transwell and tube formation assays were performed to evaluate cell motility and angiogenic potential, and the underlying mechanism via which PLAC1 knockdown inhibits BCa progression in vitro was investigated. The data revealed that PLAC1 was obviously overexpressed in BCa tissues and was associated with poor patient prognoses. Additionally, silencing PLAC1 led to reduced viability, migratory capacity, invasion potential and angiogenesis of BCa cells, including T24 and UMUC3 cells. Further investigation showed that PLAC1 knockdown modulated the phosphoinositide 3-kinase/protein kinase B/forkhead box O3a (PI3K/Akt/FOXO3a) axis by enhancing the phosphorylation of FOXO3a while suppressing the phosphorylation of PI3K as well as Akt. Moreover, we demonstrated that the inhibition of BCa progression by PLAC1 knockdown was primarily mediated through the targeting of FOXO3a. In summary, these findings confirmed the potential of PLAC1 as a promising target for suppressing BCa growth by elevating FOXO3a levels and modulating the PI3K/Akt/FOXO3a signaling axis

Heterogeneous distribution pattern of CD3+ tumor-infiltrated lymphocytes (TILs) and high combined positive score (CPS) favored the prognosis of resected early stage small-cell lung cancer

Purpose: This study aimed to illustrate the heterogeneity of immune features in small cell lung cancer (SCLC). Methods: Immunohistochemistry (IHC) staining of CD3, CD4, CD8 and PD-L1 were performed with 55 SCLC FFPE samples from radical resections. Quantitative assessment of CD3+ tumor-infiltrated lymphocytes (TILs) to present the heterogeneity in the tumor and the stroma areas. Hotspots of TILs were evaluated to illustrate the potential relationship between TIL-density and its immune competence. Programmed death ligand-1 (PD-L1) expressed on both tumor TILs (t-TILs) and stroma TILs (s-TILs) was evaluated and quantitatively described as values of tumor positive score (TPS) and combined positive score (CPS). The clinical value of TPS and CPS were further identified according to their relationship with disease-free survival (DFS). Results: More abundant CD3+ TILs were observed in the tumor stroma than that within the parenchyma (15.02±2.25% vs. 1.58±0.35%) . The amount of CD3+ s-TILs were positively correlated with DFS. The CD3+/CD4+ subset of the TILs was found more favorable to DFS compared to the CD3+/CD8+ subset. Hotspots of CD3+ TILs were observed in tumor regions and patients with more Hotspots of CD3+ TILs have better outcomes. CPS were more reliable than TPS to describe PD-L1 expression in SCLC and it was found positively correlated with tumor size and DFS. Conclusions: The immune microenvironment of SCLC was heterogeneous. Hotspots, the amount of CD3/CD4+ TILs and the CPS value were found valuable in determine the anti-tumor immunity and predicting the clinical outcome of SCLC patients

The role of sacubitril/valsartan in abnormal renal function patients combined with heart failure: a meta-analysis and systematic analysis

Aims This study aimed to investigate the efficacy and safety of sacubitril/valsartan in abnormal renal function (eGFR < 60 ml/min/1.73m2) patients combined with heart failure based on randomized controlled trials (RCTs) and observational studies.Methods The Embase, PubMed and the Cochrane Library were searched for relevant studies from inception to December 2023. Dichotomous variables were described as event counts with the odds ratio (OR) and 95% confidence interval (CI) values. Continuous variables were expressed as mean standard deviation (SD) with 95% CIs.Results A total of 6 RCTs and 8 observational studies were included, involving 17335 eGFR below 60 ml/min/1.73m2 patients combined with heart failure. In terms of efficacy, we analyzed the incidence of cardiovascular events and found that sacubitril/valsartan significantly reduced the risk of cardiovascular death or heart failure hospitalization in chronic kidney disease (CKD) stages 3–5 patients with heart failure (OR: 0.65, 95%CI: 0.54–0.78). Moreover, sacubitril/valsartan prevented the serum creatinine elevation (OR: 0.81, 95%CI: 0.68–0.95), the eGFR decline (OR: 0.83, 95% CI: 0.73–0.95) and the development of end-stage renal disease in this population (OR:0.73, 95%CI:0.60–0.89). As for safety outcomes, we did not find that the rate of hyperkalemia (OR:1.31, 95%CI:0.79–2.17) and hypotension (OR:1.57, 95%CI:0.94–2.62) were increased in sacubitril/valsartan group among CKD stages 3–5 patients with heart failure.Conclusions Our meta-analysis proves that sacubitril/valsartan has a favorable effect on cardiac function without obvious risk of adverse events in abnormal renal function patients combined with heart failure, indicating that sacubitril/valsartan has the potential to become perspective treatment for these patients

Reversible conversion-alloying of Sb2O3 as a high-capacity, high-rate, and durable anode for sodium ion batteries

Sodium ion batteries are attracting ever-increasing attention for the applications in large/grid scale energy storage systems. However, the research on novel Na-storage electrode materials is still in its infancy, and the cycling stability, specific capacity, and rate capability of the reported electrode materials cannot satisfy the demands of practical applications. Herein, a high performance Sb2O3 anode electrochemically reacted via the reversible conversion-alloying mechanism is demonstrated for the first time. The Sb2O3 anode exhibits a high capacity of 550 mAh g-1 at 0.05 A g-1 and 265 mAh g-1 at 5 A g-1. A reversible capacity of 414 mAh g-1 at 0.5 A g-1 is achieved after 200 stable cycles. The synergistic effect involving conversion and alloying reactions promotes stabilizing the structure of the active material and accelerating the kinetics of the reaction. The mechanism may offer a well-balanced approach for sodium storage to create high capacity and cycle-stable anode materials

Recent progress in epidemiology, clinical features, and therapy of multiple sclerosis in China

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system characterized by inflammation, demyelination, and neurodegeneration. It mainly affects young adults, imposing a heavy burden on families and society. The epidemiology, clinical features, and management of MS are distinct among different countries. Although MS is a rare disease in China, there are 1.4 billion people in China, so the total number of MS patients is not small. Because of the lack of specific diagnostic biomarkers for MS, there is a high misdiagnosis rate in China, as in other regions. Due to different genetic backgrounds, the clinical manifestations of MS in Chinese are different from those in the West. Herein, this review aims to summarize the disease comprehensively, including clinical profile and the status of disease-modifying therapies in China based on published population-based observation and cohort studies, and also to compare with data from other countries and regions, thus providing help to develop diagnostic guideline and the novel therapeutic drugs. Meanwhile, we also discuss the problems and challenges we face, specifically for the diagnosis and treatment of MS in the middle- and low-income countries

sketchboard: supporting natural interaction for video organization and navigation using sketching annotation

Considering the explosion of video sources, efficient techniques for interactively organizing a meaningful structure to allow easy navigating and semantic-based indexing are appealing. We explore the use of sketch based annotations for video clips to enable novel approaches to interacting with video by following hyperlinks specified by users. In this paper, we provide a sketch based interface Sketchboard, to facilitate the interaction process of navigating and organizing video clips more naturally and efficiently. The Sketchboard includes two key processes: (1) Providing a video annotator using the sketches, which enrich and enhance video indexing for navigation. (2) Supporting video organization using sketch based interface based on sketching annotations, which enables fast, flexible and personalized video organization. The informal user study showed that the presented interface enhances the accessibility and the individualization of exploring videos. &copy; 2011 IEEE.Considering the explosion of video sources, efficient techniques for interactively organizing a meaningful structure to allow easy navigating and semantic-based indexing are appealing. We explore the use of sketch based annotations for video clips to enable novel approaches to interacting with video by following hyperlinks specified by users. In this paper, we provide a sketch based interface Sketchboard, to facilitate the interaction process of navigating and organizing video clips more naturally and efficiently. The Sketchboard includes two key processes: (1) Providing a video annotator using the sketches, which enrich and enhance video indexing for navigation. (2) Supporting video organization using sketch based interface based on sketching annotations, which enables fast, flexible and personalized video organization. The informal user study showed that the presented interface enhances the accessibility and the individualization of exploring videos. &copy; 2011 IEEE