Effect of Ba-Duan-Jin on Immune Function and Autonomic Nervous Balance in Ageing People

[Objective] Ba-Duan-Jin, formed in the 12th century, is an excellent traditional Chinese health exercises. Ancients likened it to “brocade (Jin)”, meaning its action is as elegant as brocade. The total movements are divided into 8 sections, so it is called “ Ba-Duan-Jin (8-section-action)”. Because of its simple action and significantly healthy effect, Ba-Duan-Jin is widely used to enhance physical fitness and prevent diseases. This study was aimed to evaluate the immunological effect of Ba-Duan-Jin in ageing people and analyze its autonomic nervous mechanism. [Methods] 60 healthy women (64.06±2.53 years old) were divided into exercising group and sedentary group. Exercising group trained Ba-Duan-Jin 12 weeks（5 day/week, 3 repetition/day）. Record electrocardiosignal to analyze heart rate variability (HRV) , and then take blood sample to measure blood routine, immune globulin, complement, sub-T lymphocyte, catecholamines and acetylcholine. These measurements were performed before and after the 8-week’s intervening duration. [Results] The plasma immune globulin, complement, catecholamines and acetylcholine have no significant difference between two groups. But when it came to lymphocyte in peripheral blood, the women in exercising group have less CD8+ T-lymphocyte and higher rate of CD4+/CD8+ than sedentary group. The analysis of HRV showed an increasing total HRV (TF), a enhanced activity of parasympathetic nerve (RRmean, SDNN, RMSSD, HFnorm) and an attenuated activity of sympathetic nerve (LFnorm) in Ba-Duan-Jin exercising group. Correlation analysis confirmed that there is a close relationship between immune function and autonomic nervous activities. [Conclusion] Ba-Duan-Jin can transfer the autonomic nervous balance to parasympathetic dominance, which may partially explain the increasing immunity function (especially in cell immunity) in ageing people. Fig: the 8 sections of Ba-Duan-Jin Note: 1. Holding heaven in the palms2. Posing as an archer shooting3. Holding one arm aloft4. Looking backward5. Swinging the head and lowering the body6. Moving the hands down the back and legs, and touching the Feet7. Thrusting the fists and making the eyes glare8. Raising and Lowering the Heel

AI-powered Fraud Detection in Decentralized Finance: A Project Life Cycle Perspective

In recent years, blockchain technology has introduced decentralized finance (DeFi) as an alternative to traditional financial systems. DeFi aims to create a transparent and efficient financial ecosystem using smart contracts and emerging decentralized applications. However, the growing popularity of DeFi has made it a target for fraudulent activities, resulting in losses of billions of dollars due to various types of frauds. To address these issues, researchers have explored the potential of artificial intelligence (AI) approaches to detect such fraudulent activities. Yet, there is a lack of a systematic survey to organize and summarize those existing works and to identify the future research opportunities. In this survey, we provide a systematic taxonomy of various frauds in the DeFi ecosystem, categorized by the different stages of a DeFi project's life cycle: project development, introduction, growth, maturity, and decline. This taxonomy is based on our finding: many frauds have strong correlations in the stage of the DeFi project. According to the taxonomy, we review existing AI-powered detection methods, including statistical modeling, natural language processing and other machine learning techniques, etc. We find that fraud detection in different stages employs distinct types of methods and observe the commendable performance of tree-based and graph-related models in tackling fraud detection tasks. By analyzing the challenges and trends, we present the findings to provide proactive suggestion and guide future research in DeFi fraud detection. We believe that this survey is able to support researchers, practitioners, and regulators in establishing a secure and trustworthy DeFi ecosystem.Comment: 38 pages, update reference

NQO1 targeting prodrug triggers innate sensing to overcome checkpoint blockade resistance

Lack of proper innate sensing inside tumor microenvironment (TME) limits T cell-targeted immunotherapy. NAD(P)H:quinone oxidoreductase 1 (NQO1) is highly enriched in multiple tumor types and has emerged as a promising target for direct tumor-killing. Here, we demonstrate that NQO1-targeting prodrug β-lapachone triggers tumor-selective innate sensing leading to T cell-dependent tumor control. β-Lapachone is catalyzed and bioactivated by NQO1 to generate ROS in NQO1high tumor cells triggering oxidative stress and release of the damage signals for innate sensing. β-Lapachone-induced high mobility group box 1 (HMGB1) release activates the host TLR4/MyD88/type I interferon pathway and Batf3 dendritic cell-dependent cross-priming to bridge innate and adaptive immune responses against the tumor. Furthermore, targeting NQO1 is very potent to trigger innate sensing for T cell re-activation to overcome checkpoint blockade resistance in well-established tumors. Our study reveals that targeting NQO1 potently triggers innate sensing within TME that synergizes with immunotherapy to overcome adaptive resistance

The Roles of PI3K/AKT/mTOR and MAPK/ERK Signaling Pathways in Human Pheochromocytomas

Objectives. The roles of PI3K/AKT/mTOR and MAPK/ERK pathways involved in the pathogenesis of pheochromocytoma and paraganglioma (PPGL) were demonstrated mostly by in vitro studies with rat or mouse cells and were mainly studied at transcriptional level. This study aimed to investigate the effect of these pathways on the proliferation of human PPGL cells and the activation of these pathways in PPGLs. Methods. Human PPGL cells were treated with sunitinib and inhibitors of PI3K (LY294002), MEK1/2 (U0126), and mTORC1/2 (AZD8055). Cell proliferation was detected by MTT assay. Protein phosphorylation was detected by Western blotting. Results. In most PPGLs, AKT, ERK1/2, and mTOR were activated. LY294002 (10 μM), U0126 (10 μM), AZD8055 (1 μM), and sunitinib (1 μM) inhibited PPGL cell proliferation in ten primary cultures of tissues, including four from patients with gene mutations. MEK1/2 inhibitor decreased mTOR phosphorylation. Inhibition of mTOR reduced phosphorylation of AKT and ERK1/2. Sunitinib inhibited phospho-ERK1/2 and phospho-mTOR. Conclusion. Our study suggested that PI3K/AKT/mTOR and MAPK/ERK signaling pathways play vital roles in human PPGL and are activated in most PPGLs. Inhibiting multiple pathways might be a novel therapeutic approach for PPGLs

Preferences for End-of-Life Care Among Patients With Terminal Cancer in China

IMPORTANCE: In China, little is known about end-of-life (EOL) care preferences of patients with terminal cancer. Understanding these patients’ treatment preferences is needed to improve patient-centered health care, better inform surrogates and medical staff about patient preferences, and enhance the quality of EOL care. OBJECTIVE: To examine preferences for EOL care among patients with terminal cancer in China. DESIGN, SETTING, AND PARTICIPANTS: In this survey study, patients older than 50 years who had terminal cancer were randomly selected from medical records at a single hospital in China. Data on patients’ EOL care preferences were collected by discrete choice experiment (DCE) from August to November 2018 and were analyzed from October 2020 to March 2021. MAIN OUTCOMES AND MEASURES: The main outcome was patient preferences in EOL care, derived using a mixed logit model. Each DCE scenario described 6 attributes: hospitalization days, life extension, quality of life, adverse treatment events, place-of-death preference, and out-of-pocket costs. The marginal willingness to pay (WTP) in US dollars was estimated from regression coefficients. RESULTS: Of 188 patients selected for the survey, 183 participated (97.3%). Among the respondents, the mean [SD] age was 61 [8.4] years, and 128 (69.8%) were male. Patients’ preferences for moderate increase in survival time, better quality of life, death at home, and lower out-of-pocket costs were significantly associated with their choices between treatment models. Extending life by 10 months (vs 4 months: β, 1.63; 95% CI, 0.81-2.44) and a better quality of life (very good vs poor: β, 1.79; 95% CI, 0.96-2.62) were the most important attributes to patients. The uptake rate for a treatment scenario increased by 61.6% when the quality of life improved from poor to very good, and when life extension increased from 4 months to 10, the uptake rate increased by 57.2%. The uptake increased by 12.5% when the place of death changed from hospital to home. However, it decreased by 31.4% when the costs increased to $21 174. The study found a WTP of$38 854 (95% CI, $19 468-$95 096) to improve quality of life from a poor to a very good level, substantially higher than the WTP for a life extension of 6 months ($35 308; 95$17 745-$80 279) or 1 year ($27 572; 95% CI, $16 389-$58 027) compared with the baseline scenario of a 4-month extension. Patients were willing to pay $8860 (95$621-$26 474) to die at home rather than in a hospital. CONCLUSIONS AND RELEVANCE: The findings suggest that in addition to extending life moderately for patients with terminal cancer, improving quality of life during EOL care and supporting home deaths may deserve greater attention. The findings also suggest that physicians and surrogates should ask about patients’ care preferences and better inform them of their choices to improve EOL care outcomes

COMPARISON OF LABORATORY AND INDUSTRIAL SACCHAROMYCES CEREVISIAE STRAINS FOR THEIR INHIBITOR RESISTANCE AND XYLOSE UTILIZATION

There are various kinds of stresses during the process of ethanol fermentation and more inhibitory factors are produced when lignocelluloses hydrolysate is used as the substrate. The pretreatment of lignocelluloses biomass before fermentation causes the increase in the amount of acids and thus the decrease in pH. Low-molecular weight aliphatic acids, furaldehydes and a broad range of aromatic compounds are produced during the pretreatment process. They are the inhibitors for the ethanol producers, such as Saccharomyces cerevisiae. Furthermore, besides glucose, lignocellulose hydrolysate contains other sugars, such as xylose, arabinose, galactose and mannose etc., among which xylose is taking the major proportion. Stress tolerance and xylose utilization are therefore essential for Saccharomyces cerevisiae strains to get high-efficiency fermentation and high-yield ethanol production. In this study, a few laboratory and industrial Saccharomyces cerevisiae strains were selected for the evaluation of their potentials in pH tolerance, inhibitor resistance and xylose utilization. Industrial strains such as TJU (an industrial strain used in some of the bioethanol plants in China), ATCC 4126, and ATCC 96581, an isolate from spent sulfite liquor were compared with some laboratory strains such as ATCC 44771, ATCC 24860 and CBS 8066. The difference of these strains in their pH tolerance was insignificant despite the fact that almost all the strains had less growth when pH was below 4. Among all the yeast strains tested, the haploid laboratory strain ATCC 44771 showed the lowest tolerance to the decrease of pH. As to the inhibitor resistance studies almost all the industrial strains tested had higher inhibitor resistance than the laboratory strains, with ATCC 44771 being the least resistant to the increase in the inhibitor concentrations. The laboratory strain ATCC 24860 showed almost equivalent inhibitor resistance compared with these industrial strains. Further analysis of these strains on their xylose utilization was carried out. Random mutagenesis followed by xylose adaptation was applied. Almost all the laboratory strains died after mutation and all the industrial strains survived with their xylose unitization capabilities increased. In addition, the presence of inhibitors such as 5-hydroxymethylfurfural (HMF) and furfural had enhanced their xylsoe assimilation. The above analysis indicated that industrial Saccharomyces cerevisiae strains could be trained for biomass hydrolysate fermentation as they have high pH tolerance, high inhibitor resistance and potentials in xylose utilization. As such, the potential xylose-utilizing mutants are being evaluated for their potentials in biomass hydrolysate fermentation

Direct Covalent Chemical Functionalization of Unmodified Two-Dimensional Molybdenum Disulfide

Two-dimensional semiconducting transition metal dichalcogenides (TMDCs) like molybdenum disulfide (MoS2) are generating significant excitement due to their unique electronic, chemical, and optical properties. Covalent chemical functionalization represents a critical tool for tuning the properties of TMDCs for use in many applications. However, the chemical inertness of semiconducting TMDCs has thus far hindered the robust chemical functionalization of these materials. Previous reports have required harsh chemical treatments or converting TMDCs into metallic phases prior to covalent attachment. Here, we demonstrate the direct covalent functionalization of the basal planes of unmodified semiconducting MoS2 using aryl diazonium salts without any pretreatments. Our approach preserves the semiconducting properties of MoS2, results in covalent C-S bonds, is applicable to MoS2 derived from a range of different synthesis methods, and enables a range of different functional groups to be tethered directly to the MoS2 surface. Using density functional theory calculations including van der Waals interactions and atomic-scale scanning probe microscopy studies, we demonstrate a novel reaction mechanism in which cooperative interactions enable the functionalization to propagate along the MoS2 basal plane. The flexibility of this covalent chemistry employing the diverse aryl diazonium salt family is further exploited to tether active proteins to MoS2, suggesting future biological applications and demonstrating its use as a versatile and powerful chemical platform for enhancing the utility of semiconducting TMDCsComment: To appear in Chemistry Materials (In press