Subjective Cognitive Decline May Be Associated With Post-operative Delirium in Patients Undergoing Total Hip Replacement: The PNDABLE Study

Objective: Subjective cognitive decline (SCD) is associated with an increased risk of clinical cognitive disorders. Post-operative delirium (POD) is a common complication after total hip replacement. We aimed to investigate the relationship between SCD and POD in patients undergoing total hip replacement.Methods: Our study recruited 214 cognitively intact individuals from the Perioperative Neurocognitive Disorder And Biomarker Lifestyle (PNDABLE) study in the final analysis. SCD was diagnosed with Subjective Cognitive Decline Scale (SCDS), Mini-Mental State Examination (MMSE), and Montreal Cognitive Assessment (MoCA). The incidence of POD was evaluated by using Confusion Assessment Method (CAM), and POD severity was measured by using the Memorial Delirium Assessment Scale (MDAS). Preoperative cerebrospinal fluid (CSF) Aβ40, Aβ42, T-tau, and P-tau levels were measured by enzyme-linked immune-sorbent assay (ELISA).Results: Overall, the incidence of POD was 26.64% (57/214), including 32.43% (36/111) in the SCD group and 20.39% (21/103) in the NC group. With the increase of age, the incidence of POD in all age groups increased (P < 0.05). Logistic regression analysis showed that after adjusting for SCD, Aβ42, Aβ40, P-tau, and T-tau, SCD (OR 2.32, CI 1.18–4.55, P = 0.01) and the increased CSF level of P-tau (OR 1.04, CI 1.01–1.06, P < 0.001) were risk factors for POD, while the level of aβ42 (OR 0.99, CI 0.99–1.00, P < 0.001) was a protective factor for POD.Conclusion: SCD is one of the preoperative risk factors for POD.Clinical Trial Registration: This study was registered at China Clinical Trial Registry (Chictr200033439)

Transcriptional profiles of different states of cancer stem cells in triple-negative breast cancer

Abstract Breast cancer stem cells (BCSCs) are thought to be responsible for tumor initiation, metastasis and relapse. Our group and others have described markers useful in isolating BCSCs just as aldehyde dehydrogenase positive (ALDH+) or CD24−CD44+. In fact, cells which simultaneously express both sets of markers have the highest tumor initiating capacity. Although the transcriptomic profile of cells expressing each BCSC marker alone has been reported, the profile of the most tumorigenic population expressing both sets of markers has not. Here we used the biomarker combination of ALDH and CD24/CD44 to sort four populations isolated from triple-negative breast cancer (TNBC) patient-derived xenografts, and performed whole-transcriptome sequencing on each population. We systematically compared the profiles of the three states of BCSCs (ALDH+CD24−CD44+, ALDH+non-CD24−CD44+ and ALDH−CD24−CD44+) to that of the differentiated tumor cells (ALDH−non-CD24−CD44+). For the first time, we compared the ALDH+CD24−CD44+ BCSCs with the other two BCSC populations. In ALDH+CD24−CD44+ BCSCs, we identified P4HA2, PTGR1 and RAB40B as potential prognostic markers, which were virtually related to the status of BCSCs and tumor growth in TNBC cells.https://deepblue.lib.umich.edu/bitstream/2027.42/142395/1/12943_2018_Article_809.pd

Differential Effects of Tautomycetin and Its Derivatives on Protein Phosphatase Inhibition, Immunosuppressive Function and Antitumor Activity

In the present work, we studied the structure-activity relationship (SAR) of tautomycetin (TMC) and its derivatives. Further, we demonstrated the correlation between the immunosuppressive fuction, anticancer activity and protein phosphatase type 1 (PP1) inhibition of TMC and its derivatives. We have prepared some TMC derivatives via combinatorial biosynthesis, isolation from fermentation broth or chemical degradation of TMC. We found that the immunosuppressive activity was correlated with anticancer activity for TMC and its analog compounds, indicating that TMC may home at the same targets for its immunosuppressive and anticancer activities. Interestingly, TMC-F1, TMC-D1 and TMC-D2 all retained significant, albeit reduced PP1 inhibitory activity compared to TMC. However, only TMC-D2 showed immunosuppressive and anticancer activities in studies carried out in cell lines. Moreover, TMC-Chain did not show any significant inhibitory activity towards PP1 but showed strong growth inhibitory effect. This observation implicates that the maleic anhydride moiety of TMC is critical for its phosphatase inhibitory activity whereas the C1-C18 moiety of TMC is essential for the inhibition of tumor cell proliferation. Furthermore, we measured in vivo phosphatase activities of PP1 in MCF-7 cell extracts treated with TMC and its related compounds, and the results indicate that the cytotoxicity of TMC doesn't correlate with its in vivo PP1 inhibition activity. Taken together, our study suggests that the immunosuppressive and anticancer activities of TMC are not due to the inhibition of PP1. Our results provide a novel insight for the elucidation of the underlying molecular mechanisms of TMC's important biological functions

Evolutionary characteristics and genetic transmission patterns of predominant HIV-1 subtypes among men who have sex with men in China.

OBJECTIVES: Men who have sex with men (MSM) represent one of the major risk groups for HIV-1 infection in China, and the predominant subtypes among this population has changed over the last two decades. The objective of this study was to determine the evolutionary characteristics and transmission patterns of the dominant HIV-1 strains in the Chinese MSM population. METHODS: A total of 4980 published HIV-1 pol gene sequences from MSM in China were retrieved and comprehensive evolutionary and transmission analyses were then conducted. Bayesian coalescent-based methods and selection pressure analyses were used to reconstruct the time-scale and demographic history and to estimate other evolutionary parameters. Transmission patterns were characterized using network analyses. RESULTS: There were 2546 (51.12%) CRF01_AE, 1263 (25.36%) CRF07_BC, and 623 (12.51%) subtype B, accounting for 88.99% of the total sequences. From 2000 to 2016, the prevalence of CRF01_AE was stable, comprising nearly half of all sequences over time (58.33-45.38%, p=0.071). CRF07_BC increased slightly from 13.3% to 22.49% (p<0.001), while subtype B decreased dramatically from 41.67% to 9.04% (p<0.001). Demographic reconstruction showed that the greatest expansion of the HIV epidemic occurred between 1999 and 2005. CRF01_AE had a higher estimated evolutionary rate (2.97×10-3 substitutions/site/year) and exhibited more sites under positive selection (25/351 codons) compared to the other subtypes. Network analyses showed that CRF07_BC (68.29%, 84/123) had a higher proportion of cross-region networks than CRF01_AE (49.1%, 174/354) and subtype B (36.46%, 35/96) (p<0.001). CONCLUSIONS: The predominant subtypes of HIV-1 in Chinese MSM have different evolutionary characteristics and transmission patterns, which poses a significant challenge to HIV treatment and disease prevention

Modelling and optimisation on scroll expander for waste heat recovery organic Rankine cycle

Scroll expander has demonstrated high efficiency at low power range. In this paper, a generic model of a scroll expander has been developed. It can calculate the ideal expander parameters to give the optimal efficiency and prevent under- or over-expansion at any given operating conditions or fluids. The dynamic model was validated by predicting the ideal volumetric expansion ratio with ideal expansion ratio of 4.03 at 0.7 MPa pressure, and showed agreement with experimental data. The results suggested that the rate of scroll increase K in the geometric model has little effect on volumetric expansion ratio or ideal scroll length of the expander, but when expansion ratio is kept constant, lower K value results in lower leakage losses