Discovery of 5-Hydroxy-1,4-naphthoquinone (Juglone) Derivatives as Dual Effective Agents Targeting Platelet-Cancer Interplay through Protein Disulfide Isomerase Inhibition.

In this study, a series of 2- and/or 3-substituted juglone derivatives were designed and synthesized. Among them, 9, 18, 22, 30, and 31 showed stronger inhibition activity against cell surface PDI or recombinant PDI and higher inhibitory effects on U46619- and/or collagen-induced platelet aggregation than juglone. The glycosylated derivatives 18 and 22 showed improved selectivity for inhibiting the proliferation of multiple myeloma RPMI 8226 cells, and the IC50 values reached 61 and 48 nM, respectively, in a 72 h cell viability test. In addition, 18 and 22 were able to prevent tumor cell-induced platelet aggregation and platelet-enhanced tumor cell proliferation. The molecular docking showed the amino acid residues Gln243, Phe440, and Leu443 are important for the compound-protein interaction. Our results reveal the potential of juglone derivatives to serve as novel antiplatelet and anticancer dual agents, which are available to interrupt platelet-cancer interplay through covalent binding to PDI catalytic active site.

Head-to-Head Comparison of Electroacupuncture and Laser Acupuncture Effects on Autonomic Regulation and Clinical Effects in Dysmenorrhea: A Randomized Crossover Clinical Trial.

Introduction: Electroacupuncture (EA) has been applied in dysmenorrhea and has shown good efficacy. The mechanisms of EA are associated with autonomic nervous system adjustments and neuroendocrine regulation. Laser acupuncture (LA), however, has been widely investigated for its noninvasiveness. However, it remains uncertain whether LA is as effective as EA. This study aimed to compare EA and LA head to head in dysmenorrhea. Methods: A crossover, randomized clinical trial was conducted. EA or LA was applied to selected acupuncture points. Participants were randomized into two sequence treatment groups who received either EA or LA twice per week in luteal phase for 3 months followed by 2-month washout, then shifted to other groups (sequence 1: EA > LA; sequence 2: LA > EA). Outcome measures were heart rate variability (HRV), prostaglandins (PGs), pain, and quality-of-life (QoL) assessment (QoL-SF12). We also compared the effect of EA and LA in low and high LF/HF (low frequency/high frequency) status. Results: Totally, 43 participants completed all treatments. Both EA and LA significantly improved HRV activity and were effective in reducing pain (Visual Analog Scale [VAS]; EA: p < 0.001 and LA: p = 0.010) and improving QoL (SF12: EA: p < 0.001, LA, p = 0.017); although without intergroup difference. EA reduced PGs significantly (p < 0.001; δ p = 0.068). In low LF/HF, EA had stronger effects than LA in increasing parasympathetic tone in respect of percentage of successive RR intervals that differ by more than 50 ms (pNN50; p = 0.053) and very low-frequency band (VLF; p = 0.035). Conclusion: There is no significant difference between EA and LA in improving autonomic nervous system dysfunction, pain, and QoL in dysmenorrhea. EA is prominent in PGs changing and preserving vagus tone in low LF/HF; yet LA is noninvasive for those who have needle phobia. Whether LA is equivalent with EA and the mechanism warrants further study. Clinical trial identification number: NCT04178226.

The Holistic Philosophy of Traditional Chinese Medicine and Conflicts With Modern Medicine.

Traditional Chinese medicine (TCM) has sparked the public's attention for its potential in new drug development and its holistic view toward health, which is totally different from the reductionistic science of modern medicine. Although many scholars try to connect TCM with precision medicine or apply new methods and technology to integrate TCM with modern medicine, the misunderstandings and gap between TCM and modern medicine limit the development of evidence-based TCM. Traditional Chinese medicine is actually a medical science encompassing not only medicine but also philosophy and art in direct contrast to molecular-based modern medicine. As more and more multidisciplinary studies are being published, finding ways to integrate TCM with modern or precision medicine through artificial intelligence, new study design and technology may become a critical issue. This article aims to briefly review the unique philosophy of TCM and its conflicts with modern medicine, with a focus on the potential integration of TCM and modern medicine. We also provide insight for the key attributes of TCM and the associated investigation with Western research approaches.

Therapeutic effects of herbal-medicine combined therapy for COVID-19: A systematic review and meta-analysis of randomized controlled trials.

Background/Aim: Since 2019, the COVID-19 pandemic has been a devastating disease affecting global health to a great extent. Some countries have added on herbal medicines as a complementary treatment for combating COVID-19 due to the urgency of stopping the spread of this viral disease. However, whether these herbal medicines are effective is uncertain. This systematic review and meta-analysis aimed to evaluate the effects of herbal medicine combined therapy in the treatment of COVID-19. Methods: A literature search was performed following the PRISMA Statement and without language restrictions. Seven databases were searched from inception through December 2021. All selected studies were randomized clinical trials (RCTs). Comparing the effects of herbal medicine combined therapy with conventional western medicine, including improvement of clinical symptoms, chest CT images, viral conversion rate, C-reactive protein (CRP) and interleukin 6. Cochrane criteria were applied to examine the methodological quality of the enrolled trials; and meta-analysis software (RevMan 5.4.1) was used for data analysis. Results: In total, the data of 5,417 participants from 40 trials were included in this systematic review; and 28 trials were qualified for meta-analysis. The trials had medium-to-high quality based on GRADE system. Meta-analysis showed that combining herbal medicine vs conventional treatment in 1) coughing (1.43 95% CI:1.21, 1.71, p = 0.0001), 2) fever (1.09 95% CI:1.00, 1.19, p = 0.06), 3) fatigue (1.21 95% CI:1.10, 1.33, p = 0.0001); 4) CT images (1.26 95% CI:1.19, 1.34, P ≤ 0.00001), 5) viral conversion rates (1.22 95% CI:1.06, 1.40, p = 0.005) and 6) viral conversion times (-3.72 95% CI: -6.05, -1.40, p = 0.002), 7) IL6 change (1.97 95% CI: -0.72, 4.66, p = 0.15) and 8) CRP change (-7.92 95% CI: -11.30, -4.53, P ≤ 0.00001). Conclusion: Herbal medicine combined therapy significantly reduces COVID-19 clinical symptoms, improving CT images and viral conversion rates. Reported adverse events are mild. However, for certain biases in the included studies, and the need for further study on effective components of herbal medicine. Further large trials with better randomized design are warranted to definite a more definite role of herbal medicine.

Discovery of 7, 4'-dimethoxy-3-hydroxyflavone as a protease-activated receptor 4 antagonist with antithrombotic activity and less bleeding tendency in mice.

There is growing evidence of the importance of protease-activated receptor 4 (PAR4), one of thrombin receptors, as a therapeutic target in thrombotic cardiovascular diseases. In the present study, we utilized ligand-based virtual screening, bioassay, and structure-activity relationship study to discover PAR4 antagonists with new chemical scaffolds from natural origin, and examined their application as antiplatelet agents. By using these approaches, we have identified a flavonoid, 7, 4'-dimethoxy-3-hydroxyflavone, that exhibits anti-PAR4 activity. 7, 4'-Dimethoxy-3-hydroxyflavone inhibited PAR4-mediated human platelet aggregation, GPIIb/IIIa activation, and P-selectin secretion. Also, it inhibited PAR4 downstream signaling pathways, including Ca2+/protein kinase C, Akt, and MAP kinases ERK and p38, in human platelets, and suppressed PAR4-mediated ß-arrestin recruitment in CHO-K1 cells exogenously expressed human PAR4. In a microfluidic system, 7, 4'-dimethoxy-3-hydroxyflavone reduced thrombus formation on collagen-coated chambers at an arterial shear rate in recalcified whole blood. Furthermore, mice treated with 7, 4'-dimethoxy-3-hydroxyflavone were significantly protected from FeCl3-induced carotid arterial occlusions, without significantly affecting tail bleeding time. In conclusion, 7, 4'-dimethoxy-3-hydroxyflavone represents a new class of nature-based PAR4 antagonist, it shows effective in vivo antithrombotic properties with less bleeding tendency, and could be a potential candidate for developing new antiplatelet agents.

A review of the endocrine resistance in hormone-positive breast cancer.

Hormone-positive breast cancer (BC) is a unique heterogeneous disease with a favorable prognosis compared to other types of breast cancer. As tumor biology influences the prognosis and clinical treatment, a deep understanding of how the molecular mechanisms regulate hormone sensitivity or resistance is critical in improving the efficacy and overcoming the endocrine resistance. This article comprehensively reviews the endocrine resistance in hormone-positive BC from a molecular and genetic perspective, encompassing the updated treatment and developing direction. This review includes the mechanisms of hormone resistance, which vary from epigenetic changes, crosstalk between signaling networks, cell cycle aberrance, and even change in the tumor microenvironment (TME) or stem cell. These mechanisms may contribute to treatment resistance. Current targeted therapy for hormone-resistant tumors includes PI3K/AKT/mTOR and cdk4/6 inhibitors. Several relevant pathways, biomarkers, and predictor genes have also been identified. Immunotherapy so far has a relatively less crucial role in hormone-positive than in triple-negative BC. Furthermore, the methodology to identify the PDL1 is not standardized. In a molecule and gene study, next-generation sequencing with circulating tumor DNA (ctDNA) has recently appeared as a sensitive and minimally invasive tool worth investigating.

Golden berry 4ß-hydroxywithanolide E prevents tumor necrosis factor α-induced procoagulant activity with enhanced cytotoxicity against human lung cancer cells.

Inflammation in the tumor microenvironment is positively correlated with cancer progression and metastasis as well as the risk of thromboembolism in lung cancer patients. Here we show, in human non-small cell lung cancer (NSCLC) cell lines, the master inflammatory cytokine tumor necrosis factor (TNF-α) induced tissue factor expression and procoagulant activity, and these effects were potently inhibited by 4ß-hydroxywithanolide E (4HW), a natural compound isolated from Physalis peruviana. Furthermore, combination of 4HW and TNF-α caused synergistic cytotoxicity against NSCLC cells by inducing caspase-dependent apoptosis. The underlying mechanism by which 4HW reverses the procoagulant effect of TNF-α but enhances its cytotoxic effect appears to be due to inhibition of NF-κB, which is a key switch for both inflammation-induced coagulation and cell survival. Our results suggest that 4HW may have a potential application for treating inflammation-derived cancer progression and cancer-associated hypercoagulable state.

12-Deoxyphorbol Esters Induce Growth Arrest and Apoptosis in Human Lung Cancer A549 Cells Via Activation of PKC-δ/PKD/ERK Signaling Pathway.

Prostratin, a non-tumor promoting 12-deoxyphorbol ester, has been reported as a protein kinase C (PKC) activator and is shown to have anti-proliferative activity in certain cancer cell types. Here we show that GRC-2, a prostratin analogue isolated from Euphorbia grandicornis, is ten-fold more potent than prostratin for inhibiting the growth of human non-small cell lung cancer (NSCLC) A549 cells. Flow cytometry assay revealed that GRC-2 and prostratin inhibited cell cycle progression at the G2/M phase and induced apoptosis. The cytotoxic effect of GRC-2 and prostratin was accompanied by activation and nuclear translocation of PKC-δ and PKD as well as hyperactivation of extracellular signal-related kinase (ERK). Knockdown of either PKC-δ, PKD or ERK significantly protected A549 cancer cells from GRC-2- and prostratin-induced growth arrest as well as apoptosis. Taken together, our results have shown that prostratin and a more potent analogue GRC-2 reduce cell viability in NSCLC A549 cells, at least in part, through activation of the PKC-δ/PKD/ERK pathway, suggesting the potential of prostratin and GRC-2 as anticancer agents.

The Efficacy of Acupuncture in Chemotherapy-Induced Peripheral Neuropathy: Systematic Review and Meta-Analysis.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) has no cure, but acupuncture may provide relief through its known neuromodulation or neuroendocrine adjustment. This review aimed to assess the efficacy of acupuncture in treating CIPN. Method: A literature review following the PRISMA Statement was performed, searching 7 databases from inception through August 2019. All studies were clinical trials of the effect of acupuncture on CIPN. The methodological quality of these trials was assessed using Cochrane criteria; meta-analysis software (RevMan 5.2) was used to analyze the data. Data Sources: The databases searched were the following: MEDLINE (Ovid), Embase, Cochrane CENTRAL, Scopus, World Health Organization International Clinical Trials Registry Platform, CNKI (China National Knowledge Infrastructure), and Wanfang Med Online. Results: We examined 386 cancer patients from 6 randomized control trials, which had high quality, based on the modified Jadad scale. Meta-analysis showed that acupuncture led to significant improvements in pain scores (-1.21, 95% confidence interval [CI] = -1.61 to -0.82, P < .00001) and nervous system symptoms based on Functional Assessment of Cancer Therapy/Neurotoxicity questionnaire scores (-2.02, 95% CI = -2.21 to -1.84, P < .00001). No significant change was noted in nerve conduction velocity (1.58, 95% CI = -2.67 to 5.83, P = .47). Conclusion: Acupuncture can effectively relieve CIPN pain and functional limitation. The limited number of subjects warrants a larger scale study.

Presence of Bacillus coagulans spores and vegetative cells in rat intestine and feces and their physiological effects.

This study was aimed to investigate the presence of Bacillus coagulans vegetative cells in the intestine and fecal samples in rats fed B. coagulans spores as well as to estimate the ratios of spores and vegetative cells in these samples. A two-step process has been developed to enumerate B. coagulans in different mixed bacterial samples, specifically (1) observation of yellow ring formation on modified GYEA medium upon incubation at 55°C, (2) microscopic examination of spore formation after 7 d of incubation. Our results have demonstrated the presence of vegetative cells in the intestinal and fecal samples in rats fed B. coagulans spores. The ratios of B. coagulans spores and vegetative cells in cecal fluid, colonic content, and feces were approximately 2:8, 2:8, and 4:6, respectively. The existence of B. coagulans vegetative cells improved the intestinal milieu through an elevated short-chain fatty acid concentrations, higher fecal moisture, and lower fecal pH.

The Effect of Acupuncture in Breast Cancer-Related Lymphoedema (BCRL): A Systematic Review and Meta-Analysis.

Background: Breast cancer-related lymphedema (BCRL) is hard to control. Management may include lymphatic drainage, skin care, bandaging, or even surgery. Since acupuncture has been proven to affect the neurophysiology and neuroendocrine systems, it has the potential to control BCRL. Aim: To evaluate the effect of acupuncture in BCRL in randomized controlled trials. Design: A literature search was performed, following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement and without language restrictions. Data Sources: Five databases were searched from inception tthrough September 2018. Only studies that fulfilled the eligibility criteria of evaluating the effect of acupuncture on lymphedema in breast cancer were included. The methodological quality of these trials was assessed using the Cochrane criteria, and meta-analysis software (RevMan 5.3) was used for analysis. Results: We examined 178 breast cancer patients from 6 trials. All included randomized controlled trials had medium to high quality, based on the modified Jadad scale. The systematic review showed that acupuncture is safe and has a trend to improve symptoms, but trials did not consistently measure outcomes. The meta-analysis showed that acupuncture produced no significant improvement in the extent of lymphedema as compared with the control intervention (-1.90; 95% confidence interval = -5.39 to 1.59, P = .29). None of the studies reported severe adverse events. Conclusions: Acupuncture is safe and has a trend to improve the lymphedema related to breast cancer, yet it did not significantly change arm circumference in BCRL. Future studies should include both subjective and objective measurements and large-scale studies are warranted.

Selective Inhibition of PAR4 (Protease-Activated Receptor 4)-Mediated Platelet Activation by a Synthetic Nonanticoagulant Heparin Analog.

Objective- PAR4 (protease-activated receptor 4), one of the thrombin receptors in human platelets, has emerged as a promising target for the treatment of arterial thrombotic disease. Previous studies implied that thrombin exosite II, known as a binding site for heparin, may be involved in thrombin-induced PAR4 activation. In the present study, a heparin octasaccharide analog containing the thrombin exosite II-binding domain of heparin was chemically synthesized and investigated for anti-PAR4 effect. Approach and Results- PAR4-mediated platelet aggregation was examined using either thrombin in the presence of a PAR1 antagonist or γ-thrombin, which selectively activates PAR4. SCH-28 specifically inhibits PAR4-mediated platelet aggregation, as well as the signaling events downstream of PAR4 in response to thrombin. Moreover, SCH-28 prevents thrombin-induced ß-arrestin recruitment to PAR4 but not PAR1 in Chinese Hamster Ovary-K1 cells using a commercial enzymatic complementation assay. Compared with heparin, SCH-28 is more potent in inhibiting PAR4-mediated platelet aggregation but has no significant anticoagulant activity. In an in vitro thrombosis model, SCH-28 reduces thrombus formation under whole blood arterial flow conditions. Conclusions- SCH-28, a synthetic small-molecular and nonanticoagulant heparin analog, inhibits thrombin-induced PAR4 activation by interfering with thrombin exosite II, a mechanism of action distinct from other PAR4 inhibitors that target the receptor. The characteristics of SCH-28 provide a new strategy for targeting PAR4 with the potential for the treatment of arterial thrombosis.

Changes in physicochemical properties of corn starch upon modifications by atmospheric pressure plasma jet.

The influences of atmospheric pressure plasma jet on different physicochemical properties of corn starch were evaluated after treated with the plasma jet (30 min) at different strengths (400 W-800 W). Our results demonstrated that residual aging effects of plasma on starch could be eliminated by washing the treated samples with distilled water at a ratio of 1:30, w/v. After plasma and washing treatments, significant (p < 0.05) reductions in pasting properties including peak viscosity, final viscosity, and setback of starch samples (up to -87.1%, -92.0%, and -93.3%, respectively) were observed with increasing plasma intensity. Apparently, plasma jet could increase the solubility and paste clarity of starch sample. Surface morphological characterization illustrated that plasma etching resulted in some physical changes on starch granules. Modifications in these physicochemical properties of corn starch by employing the plasma jet treatment might be useful in food applications requiring starch ingredients of low viscosity and high paste clarity.

DNA Damage Response/TP53 Pathway Is Activated and Contributes to the Pathogenesis of Dilated Cardiomyopathy Associated With LMNA (Lamin A/C) Mutations.

RATIONALE: Mutations in the LMNA gene, encoding LMNA (lamin A/C), are responsible for laminopathies. Dilated cardiomyopathy (DCM) is a major cause of mortality and morbidity in laminopathies. OBJECTIVE: To gain insights into the molecular pathogenesis of DCM in laminopathies. METHODS AND RESULTS: We generated a tet-off bigenic mice expressing either a WT (wild type) or a mutant LMNA (D300N) protein in cardiac myocytes. LMNAD300N mutation is associated with DCM in progeroid syndromes. Expression of LMNAD300N led to severe myocardial fibrosis, apoptosis, cardiac dysfunction, and premature death. Administration of doxycycline suppressed LMNAD300N expression and prevented the phenotype. Whole-heart RNA sequencing in 2-week-old WT and LMNAD300N mice led to identification of ≈6000 differentially expressed genes. Gene Set Enrichment and Hallmark Pathway analyses predicted activation of E2F (E2F transcription factor), DNA damage response, TP53 (tumor protein 53), NFκB (nuclear factor κB), and TGFß (transforming growth factor-ß) pathways, which were validated by Western blotting, quantitative polymerase chain reaction of selected targets, and immunofluorescence staining. Differentially expressed genes involved cell death, cell cycle regulation, inflammation, and epithelial-mesenchymal differentiation. RNA sequencing of human hearts with DCM associated with defined LMNA pathogenic variants corroborated activation of the DNA damage response/TP53 pathway in the heart. Increased expression of CDKN2A (cyclin-dependent kinase inhibitor 2A)-a downstream target of E2F pathway and an activator of TP53-provided a plausible mechanism for activation of the TP53 pathway. To determine pathogenic role of TP53 pathway in DCM, Tp53 gene was conditionally deleted in cardiac myocytes in mice expressing the LMNAD300N protein. Deletion of Tp53 partially rescued myocardial fibrosis, apoptosis, proliferation of nonmyocyte cells, left ventricular dilatation and dysfunction, and slightly improved survival. CONCLUSIONS: Cardiac myocyte-specific expression of LMNAD300N, associated with DCM, led to pathogenic activation of the E2F/DNA damage response/TP53 pathway in the heart and induction of myocardial fibrosis, apoptosis, cardiac dysfunction, and premature death. The findings denote the E2F/DNA damage response/TP53 axis as a responsible mechanism for DCM in laminopathies and as a potential intervention target.

Different effects of 4ß-hydroxywithanolide E and withaferin A, two withanolides from Solanaceae plants, on the Akt signaling pathway in human breast cancer cells.

BACKGROUND: Triple-negative breast cancer (TNBC) represents a clinical challenge because it lacks sensitivity to hormone therapy or other available molecule-targeted agents. In addition, TNBC frequently exhibits over-activation of the PI3K/Akt survival pathway that can contribute to chemotherapy resistance. 4ß-Hydroxywithanolide E (4-HW) and withaferin A (WA) are two withanolides from Solanaceae plants that exhibit promising anticancer activity in vitro and in vivo. PURPOSE: The aim of this study is to investigate and compare the effects of 4-HW and WA on TNBC cells and underling mechanisms. STUDY DESIGN/METHODS: The anticancer effects of 4-HW and WA were evaluated by cell viability, cell cycle arrest, and apoptosis assays. PI3K/Akt signaling and the expression of survivin, Bcl-2 family proteins and cyclin-dependent kinase inhibitors were evaluated by Western blot. The role of PI3K/Akt signaling in the withanolides-induced anticancer effects was examined by using a PI3K inhibitor and overexpression of a constitutively active form of Akt. RESULTS: In TNBC MDA-MB-231 cells, 4-HW and WA displayed different kinetic effect on cell availability. Cell cycle analysis revealed that 4-HW induced the G1-phase arrest while WA caused the G2/M-phase block. Both withanolides induced apoptosis, but WA also caused necrosis. 4-HW inhibited the PI3K/Akt pathway and survivin expression as well as up-regulated the cyclin-dependent kinase inhibitors p21 and p27. In contrast, WA is a more potent inhibitor of Hsp90 and elicited Akt activation at low doses but inhibited Akt signaling at higher doses by depleting the Akt protein. The PI3K inhibitor LY294002 mimicked the effects of 4-HW and potentiated the cytotoxic activity of WA. In contrast, overexpressing a constitutively active form of myristoylated Akt rescue cancer cells from 4-HW-induced cell death. CONCLUSION: The withanolides 4-HW and WA potently inhibit the viability of TNBC cells through induction of cell cycle arrest and apoptosis/necrosis. The PI3K/Akt pathway plays distinct roles in cancer cells respond to 4-HW and WA. These results suggest the potential applications of the withanolides for the treatment of TNBC.

The chemopreventive isothiocyanate sulforaphane reduces anoikis resistance and anchorage-independent growth in non-small cell human lung cancer cells.

The capacity of cancer cells to resist detachment-induced apoptosis, i.e. anoikis, as well as anchorage-independent growth are crucial prerequisites for tumor metastasis. Therefore, agents interfering these properties may provide novel anti-metastatic strategies. Sulforaphane (SFN), an isothiocyanate found in cruciferous vegetables, is known as a potent chemopreventive agent, but its effect on anoikis resistance has not been investigated. In this study, two non-small cell lung cancer (NSCLC) cell lines, A549 and CL1-5 cells, were treated with SFN under either suspension or adhesion conditions. SFN exhibited more potent cytotoxicity against suspending rather than adherent cancer cells. The selective cytotoxicity was due to the induction of anoikis, as evident by chromatin condensation, Annexin V binding, and activation of the mitochondrial apoptotic pathway. SFN also inhibited NSCLC cell to form spherical colonies, suggesting that anchorage-independent growth was prevented by SFN. Consistently, SFN treatment led to inactivation of FAK and Akt, down-regulation of ß-catenin, and up-regulation of the cyclin-dependent kinase inhibitor p21. Because A549 cells with wild-type p53 are more sensitive to SFN than p53-mutant CL1-5 cells, p53 dependency of SFN responses were determined in p53-knockdown A549 cells. Knockdown of p53 attenuated the ability of SNF to inhibit anoikis resistance and sphere formation in A549 cancer cells, suggesting that the presence of p53 in NSCLC cancer cells is involved in the sensitivity to SFN. These results provide new insight into mechanisms underlying the chemopreventive ability of SFN and suggest a potential benefit of SFN to interfere with tumor metastasis.

A Reliability Scheduling Algorithm for the Static Segment of FlexRay on Vehicle Networks.

FlexRay is a next-generation in-vehicle communication protocol which works in real time with flexibility. The most common applications in FlexRay are high bandwidth. X-by-wire applications, such as brake by wire and throttle by wire. However, there is no mechanism which can prevent transient faults in the application layer of FlexRay. If a transient fault occurs during driving, this would be very dangerous; therefore, we propose a fast reliability scheduling algorithm (FRSA) to improve the communication reliability of FlexRay. The proposed method reduces the probability of transient faults in one clock cycle by using a retransmission mechanism to recover the transient errors, and further improves computational complexity using the lookup table method to ensure system reliability. In this paper, we analyze a related literature to establish the system reliability constraints needed to evaluate the necessary time and slot usage, and the proposed cost function is used to evaluate the performance and efficiency when the number of messages is increased. Experimental results show that the proposed FRSA reduces execution time by an average 70.76% and cost by an average 13.33% more than the other existing methods. This method can be useful to others, especially regarding research about periodic time-triggered communication systems.

Inclusion of Fructooligosaccharide and Resistant Maltodextrin in High Fat Diets Promotes Simultaneous Improvements on Body Fat Reduction and Fecal Parameters.

This study investigated the effects of incorporating a mixture of fructooligosaccharide (FOS) and resistant maltodextrin (RMD) at a ratio of 1:2 on body fat accumulation and fecal bacterial parameters in rats. Our results indicated that high dietary fat consumption might effectively (p < 0.05) increase body fat, but consequently inducing a significantly (p < 0.05) higher growth of C. perfringens and retarded growth (p < 0.05) of the Bifidobacterium spp. in the large intestine. As compared with the high fat control, an incorporation of the FOS and RMD mixture at a high dose (0.97 and 1.94 g/kg body weight, respectively) could result in a significant (p < 0.05) reduction in feed efficiency (-16%), total visceral fat (-17.4%), non-visceral fat levels (-20.3%), and total body fat (-19.2%). Furthermore, feeding the FOS and RMD mixture at a high dose was capable to counter the above undesirable impacts by reducing the C. perfringens count (-14.8%) and increasing the total Bifidobacterium count (134.4%) and total fecal short chain fatty acids (195.4%). A supplementation of adequate amount of FOS and RMD might confer a concreted solution to the obesity and deteriorated fecal bacteria profiles due to high fat consumption.

The Effects of a Mindfulness Meditation Program on Quality of Life in Cancer Outpatients: An Exploratory Study.

OBJECTIVE: Numerous studies have investigated the efficacy of mindfulness meditation (MM) in managing quality of life (QoL) in cancer populations, yet only a few have studied the Asian population. The aim of this exploratory study is to evaluate the effect of a MM program on the QoL outcomes in Taiwanese cancer outpatients. METHODS: Patients with various cancer diagnoses were enrolled and assigned to the MM group and usual care (UC) group. The meditation intervention consisted of 3 sessions held monthly. The outcomes of the whole intervention were measured using the World Health Organization Quality of Life (WHOQOL-BREF) instrument. RESULTS: A total of 35 participants in the MM group and 34 in the UC group completed the study. The results showed that the postintervention scores were significantly higher than the preintervention scores in the MM group. In the UC group, there was no significant difference between preintervention and postintervention scores, except for the lower environment domain scores. There was no significant difference between the follow-up scores and postintervention scores in the MM group, indicating that improvement can be maintained for 3 months after completing the MM course. CONCLUSIONS: The present study provides preliminary outcomes of the effects on the QoL in Taiwanese cancer patients. The results suggest that MM may serve as an effective mind-body intervention for cancer patients to improve their QoL, and the benefits can persist over a 3-month follow-up period. This occurred in a diverse cancer population with various cancer diagnoses, strengthening the possibility of general use.

Effect of acupuncture on hot flush and menopause symptoms in breast cancer- A systematic review and meta-analysis.

BACKGROUND: Many breast cancer patients suffer from hot flush and medical menopause as side effects of treatment. Some patients undergo acupuncture, rather than hormone therapy, to relieve these symptoms, but the efficacy of acupuncture is uncertain. This meta-analysis evaluated the efficacy of acupuncture on hot flush and menopause symptoms in women with breast cancer. METHODS: A literature search was performed, following the PRISMA Statement and without language restrictions, of 7 databases from inception through March 2017. All selected studies were randomized clinical trials (RCTs) that examined the effect of needle acupuncture on hot flush and menopause symptoms in patients with breast cancer. The methodological quality of these trials was assessed using Cochrane criteria, and meta-analysis software (RevMan 5.2) was used to analyze the data. RESULTS: We examined 844 breast cancer patients (average age: 58 years-old) from 13 RCTs. The trials had medium-to-high quality, based on the modified Jadad scale. The meta-analysis showed that acupuncture had no significant effect on the frequency and the severity of hot flush (p = 0.34; p = 0.33), but significantly ameliorated menopause symptoms (p = 0.009). None of the studies reported severe adverse events. CONCLUSIONS: Acupuncture significantly alleviated menopause symptoms, but had no effect on hot flush. Breast cancer patients concerned about the adverse effects of hormone therapy should consider acupuncture. Further large-scale studies that also measure biomarkers or cytokines may help to elucidate the mechanism by which acupuncture alleviates menopause symptoms in patients with breast cancer.