Perioperative probiotics attenuates postoperative cognitive dysfunction in elderly patients undergoing hip or knee arthroplasty: A randomized, double-blind, and placebo-controlled trial

BackgroundPostoperative cognitive dysfunction (POCD) is a common complication in elderly patients following surgery. The preventive and/or treatment strategies for the incidence remain limited.ObjectiveThis study aimed to investigate the preventive effect of perioperative probiotic treatment on POCD in elderly patients undergoing hip or knee arthroplasty.MethodsAfter obtaining ethical approval and written informed consent, 106 patients (age ≥60 years) were recruited, who scheduled elective hip or knee arthroplasty, from 16 March 2021 to 25 February 2022 for this randomized, double-blind, and placebo-controlled trial. They were randomly assigned with a 1:1 ratio to receive either probiotics or placebo treatment (four capsules, twice/day) from hospital admission until discharge. Cognitive function was assessed with a battery of 11 neuropsychological tests on the admission day and the seventh day after surgery, respectively.ResultsA total of 96 of 106 patients completed the study, and their data were finally analyzed. POCD occurred in 12 (26.7%) of 45 patients in the probiotic group and 29 (56.9%) of 51 patients in the placebo group (relative risk [RR], 0.47 [95% confidence interval [CI], 0.27 to 0.81]; P = 0.003). Among them, mild POCD occurred in 11 (24.4%) in the probiotic group and 24 (47.1%) in the placebo group (RR, 0.52 [95% CI, 0.29 to 0.94]; P = 0.022). No significant difference in severe POCD incidence was found between the two groups (P = 0.209). Compared with the placebo group, the verbal memory domain cognitive function was mainly improved in the probiotic group.ConclusionProbiotics may be used perioperatively to prevent POCD development and improve verbal memory performance in elderly patients receiving hip or knee arthroplasty.Clinical trial registrationwww.chictr.org.cn, identifier: ChiCTR2100045620

Angiopoietin-like 4 (ANGPTL4) Suppression Ameliorates Lupus Nephritis in MRL/lpr Mice by Inactivating NLRP3 Inflammasome and Inhibiting Inflammatory Response

Background: Lupus nephritis (LN) refers to the injury caused by systemic lupus erythematosus (SLE) involving the kidneys. A previous study identified angiopoietin-like protein 4 (ANGPTL4) as a novel urinary biomarker for tracking disease activity in LN.Objective: To investigate the detailed role and regulatory mechanism of ANGPTL4 in experimental models of LN.Methods: MRL/lpr mice 11-week-old were injected with adeno-associated virus (AAV)-mediated ANGPTL4 short hairpin RNA (shRNA). At 16 and 20 weeks of age, 24-h urine samples were harvested to measure proteinuria levels. After the mice were sacrificed, blood and kidney tissues were harvested to examine serum creatinine (cr) and blood urea nitrogen (BUN) levels, kidney histological changes, and pro-inflammatory cytokine production. Additionally, the levels of NLRP3 inflammasome-associated molecules in mouse renal tissues were detected to clarify the underlying mechanism.Results: The AAV-sh-ANGPTL4 injection significantly reduced the proteinuria, cr, and BUN levels in MRL/lpr mice. ANGPTL4 silencing ameliorated glomerular, tubular, and interstitial damage in mice, mitigating the pathological alternations of LN. In addition, ANGPTL4 knockdown repressed pro-inflammatory cytokine production in the kidneys. Mechanically, ANGPTL4 suppression inhibited NLRP3 inflammasome expression in renal tissues of mice.Conclusion: ANGPTL4 silencing inhibits the NLRP3 inflammasome-mediated inflammatory response, thereby ameliorating LN in MRL/lpr mice

Active Pin1 is a key target of all-trans retinoic acid in acute promyelocytic leukemia and breast cancer

A common key regulator of oncogenic signaling pathways in multiple tumor types is the unique isomerase Pin1. However, available Pin1 inhibitors lack the required specificity and potency. Using mechanism-based screening, here we find that all-trans retinoic acid (ATRA)--a therapy for acute promyelocytic leukemia (APL) that is considered the first example of targeted therapy in cancer, but its drug target remains elusive--inhibits and degrades active Pin1 selectively in cancer cells by directly binding to the substrate phosphate- and proline-binding pockets in the Pin1 active site. ATRA-induced Pin1 ablation degrades the fusion oncogene PML-RARα and treats APL in cell and animal models and human patients. ATRA-induced Pin1 ablation also inhibits triple negative breast cancer cell growth in human cells and in animal models by acting on many Pin1 substrate oncogenes and tumor suppressors. Thus, ATRA simultaneously blocks multiple Pin1-regulated cancer-driving pathways, an attractive property for treating aggressive and drug-resistant tumors

Methodology for Regulating the Management of Sea Areas

罗曼丽，西南政法大学法律硕士，现任职于宁波市海洋与渔业局法规处【中文摘要】2002年1月1日生效的《中华人民共和国海域使用管理法》规定 了海域国家所有制度和不完整的海域使用权流转制度。但是，该法的规定比较原 则、可操作性差，如何真正实现该法的立法初衷是实践中急需研究解决的问题。本文通过对我国目前海域使用权一级市场确权发证、二级市场流转现状的介绍以及对两个层面上存在问题的分析，提出对海域进行规范管理的建设性意见，在此基础上概括了为实现上述目的当前必须做的配套工作，力图建构我国科学、合理 的海域权属管理制度，从而为发展我国海洋经济提供制度支持。 【Abstract】The Law on the Management of Sea Area Use of the People's Republic of China, effective on 1 January 2002, provides a regime for the State ownership of sea areas and a system, though incomplete, for the circulation of the sea use right. The Law, more of principles, is difficult to implement. The question on how to achieve the purpose of the legislators should be resolved as soon as possible in practice. The paper presents the status quo of ascertainment of the sea use right in the primary market arid the circulation of the sea use right in the secondary market. It goes on to analyze the problems existing in these markets and provide constructive opinions with respect to the regulation of the management of sea areas. Based on it, it sums up the supporting work that needs to be done in order to help achieve the target, to build up a scientific and reasonable title management system for sea areas and to provide systemic support to the marine economy of China

Does the Self-Identity of Chinese Farmers in Rural Tourism Destinations Affect Their Land-Responsibility Behaviour Intention? The Mediating Effect of Multifunction Agriculture Perception

Farmers are the heart of rural tourism destinations, and their land-responsibility behaviours affect sustainable development. In this study, four rural tourist sites in the suburbs of Chengdu were selected, and the structural equation model was used to analyse the influence of farmers’ self-identity on their land-responsibility behaviours intention under the condition of agricultural multifunction perception as a mediation variable. The results show that, in rural tourism destinations of suburban districts of China, farmers’ self-identity is an important variable that affects their land-responsibility behaviour intention. Agricultural economic function perception mediates the relationship between farmers’ self-identity and land-responsibility behaviour intention. Agricultural non-economic function perception positively affects their agricultural economic function perception

Constraint Programming Based Biomarker Optimization

Efficient and intuitive characterization of biological big data is becoming a major challenge for modern bio-OMIC based scientists. Interactive visualization and exploration of big data is proven to be one of the successful solutions. Most of the existing feature selection algorithms do not allow the interactive inputs from users in the optimizing process of feature selection. This study investigates this question as fixing a few user-input features in the finally selected feature subset and formulates these user-input features as constraints for a programming model. The proposed algorithm, fsCoP (feature selection based on constrained programming), performs well similar to or much better than the existing feature selection algorithms, even with the constraints from both literature and the existing algorithms. An fsCoP biomarker may be intriguing for further wet lab validation, since it satisfies both the classification optimization function and the biomedical knowledge. fsCoP may also be used for the interactive exploration of bio-OMIC big data by interactively adding user-defined constraints for modeling

H2O2-Responsive Nanoparticle Based on the Supramolecular Self-Assemble of Cyclodextrin

Designing stimuli responsive, controllable and biocompatible multifunctional nanoparticles is an important progress in the current quest for drug delivery systems. Herein, we devoted to developing a β-cyclodextrin (β-CD) based drug delivery nanoparticles (NPs) that release Bovine serum albumin (BSA) via glucose-responsive gate. The design involves synthesis of sodium alginate with β-CD modified (Alg-β-CD) and methoxypolyethylene glycol (mPEG-Fc) containing ferrocene (Fc) uncharged end-capping. When α-cyclodextrin (α-CD) was added with these two segments, the stable non-covalent supramolecular structure of Alg-β-CD/mPEG-Fc/α-CD can be self-assembled into NPs in aqueous solution. BSA loaded Alg-β-CD/mPEG-Fc/α-CD also has been prepared. Interestingly, these supramolecular Alg-β-CD/mPEG-Fc/α-CD/BSA NPs showed uniform sphere structure and constant BSA loading content. Also, this new kind of NPs can disassemble in the present of hydrogen peroxide (H2O2). Since glucose oxidase (GOD) can oxidize glucose and produce H2O2, so this kind of polymeric NPs can also have glucose responsive behavior in the GOD containing environment. Developed functional Alg-β-CD/mPEG-Fc/α-CD might be a promising drug delivery strategy for diabetes or immunotherapy with more efficiency

Nucleolin down-regulation is involved in ADP-induced cell cycle arrest in S phase and cell apoptosis in vascular endothelial cells.

High concentration of extracellular ADP has been reported to induce cell apoptosis, but the molecular mechanisms remain not fully elucidated. In this study, we found by serendipity that ADP treatment of human umbilical vein endothelial cells (HUVEC) and human aortic endothelial cells (HAEC) down-regulated the protein level of nucleolin in a dose- and time-dependent manner. ADP treatment did not decrease the transcript level of nucloelin, suggesting that ADP might induce nucleolin protein degradation. HUVEC and HAEC expressed ADP receptor P2Y13 receptor, but did not express P2Y1 or P2Y12 receptors. However, P2Y1, 12, 13 receptor antagonists MRS2179, PSB0739, MRS2211 did not inhibit ADP-induced down-regulation of nucleolin. Moreover, MRS2211 itself down-regulated nucleolin protein level. In addition, 2-MeSADP, an agonist for P2Y1, 12 and 13 receptors, did not down-regulate nucleolin protein. These results suggested that ADP-induced nucleolin down-regulation was not due to the activation of P2Y1, 12, or 13 receptors. We also found that ADP treatment induced cell cycle arrest in S phase, cell apoptosis and cell proliferation inhibition via nucleolin down-regulation. The over-expression of nucleolin by gene transfer partly reversed ADP-induced cell cycle arrest, cell apoptosis and cell proliferation inhibition. Furthermore, ADP sensitized HUVEC to cisplatin-induced cell death by the down-regulation of Bcl-2 expression. Taken together, we found, for the first time to our knowledge, a novel mechanism by which ADP regulates cell proliferation by induction of cell cycle arrest and cell apoptosis via targeting nucelolin