An ERK5-NRF2 Axis Mediates Senescence-Associated Stemness and Atherosclerosis.

BACKGROUND: ERK5 (extracellular signal-regulated kinase 5) is a dual kinase transcription factor containing an N-terminal kinase domain and a C-terminal transcriptional activation domain. Many ERK5 kinase inhibitors have been developed and tested to treat cancer and inflammatory diseases. However, recent data have raised questions about the role of the catalytic activity of ERK5 in proliferation and inflammation. We aimed to investigate how ERK5 reprograms myeloid cells to the proinflammatory senescent phenotype, subsequently leading to atherosclerosis. METHODS: A ERK5 S496A (dephosphorylation mimic) knock in (KI) mouse model was generated using CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat-associated 9), and atherosclerosis was characterized by hypercholesterolemia induction. The plaque phenotyping in homozygous ERK5 S496A KI and wild type (WT) mice was studied using imaging mass cytometry. Bone marrow-derived macrophages were isolated from hypercholesterolemic mice and characterized using RNA sequencing and functional in vitro approaches, including senescence, mitochondria reactive oxygen species, and inflammation assays, as well as by metabolic extracellular flux analysis. RESULTS: We show that atherosclerosis was inhibited in ERK5 S496A KI mice. Furthermore, ERK5 S496 phosphorylation mediates both senescence-associated secretory phenotype and senescence-associated stemness by upregulating AHR (aryl hydrocarbon receptor) in plaque and bone marrow-derived macrophages isolated from hypercholesterolemic mice. We also discovered that ERK5 S496 phosphorylation could induce NRF2 (NFE2-related factor 2) SUMOylation at a novel K518 site to inhibit NRF2 transcriptional activity without altering ERK5 catalytic activity and mediates oxidized LDL (low-density lipoprotein)-induced senescence-associated secretory phenotype. Specific ERK5 kinase inhibitors (AX15836 and XMD8-92) also inhibited ERK5 S496 phosphorylation, suggesting the involvement of ERK5 S496 phosphorylation in the anti-inflammatory effects of these ERK5 kinase inhibitors. CONCLUSIONS: We discovered a novel mechanism by which the macrophage ERK5-NRF2 axis develops a unique senescence-associated secretory phenotype/stemness phenotype by upregulating AHR to engender atherogenesis. The finding of senescence-associated stemness phenotype provides a molecular explanation to resolve the paradox of senescence in proliferative plaque by permitting myeloid cells to escape the senescence-induced cell cycle arrest during atherosclerosis formation.

Epigenetic Induction of Smooth Muscle Cell Phenotypic Alterations in Aortic Aneurysms and Dissections.

BACKGROUND: Smooth muscle cell (SMC) phenotypic switching has been increasingly detected in aortic aneurysm and dissection (AAD) tissues. However, the diverse SMC phenotypes in AAD tissues and the mechanisms driving SMC phenotypic alterations remain to be identified. METHODS: We examined the transcriptomic and epigenomic dynamics of aortic SMC phenotypic changes in mice with angiotensin II-induced AAD by using single-cell RNA sequencing and single-cell sequencing assay for transposase-accessible chromatin. SMC phenotypic alteration in aortas from patients with ascending thoracic AAD was examined by using single-cell RNA sequencing analysis. RESULTS: Single-cell RNA sequencing analysis revealed that aortic stress induced the transition of SMCs from a primary contractile phenotype to proliferative, extracellular matrix-producing, and inflammatory phenotypes. Lineage tracing showed the complete transformation of SMCs to fibroblasts and macrophages. Single-cell sequencing assay for transposase-accessible chromatin analysis indicated that these phenotypic alterations were controlled by chromatin remodeling marked by the reduced chromatin accessibility of contractile genes and the induced chromatin accessibility of genes involved in proliferation, extracellular matrix, and inflammation. IRF3 (interferon regulatory factor 3), a proinflammatory transcription factor activated by cytosolic DNA, was identified as a key driver of the transition of aortic SMCs from a contractile phenotype to an inflammatory phenotype. In cultured SMCs, cytosolic DNA signaled through its sensor STING (stimulator of interferon genes)-TBK1 (tank-binding kinase 1) to activate IRF3, which bound and recruited EZH2 (enhancer of zeste homolog 2) to contractile genes to induce repressive H3K27me3 modification and gene suppression. In contrast, double-stranded DNA-STING-IRF3 signaling induced inflammatory gene expression in SMCs. In Sting-/- mice, the aortic stress-induced transition of SMCs into an inflammatory phenotype was prevented, and SMC populations were preserved. Finally, profound SMC phenotypic alterations toward diverse directions were detected in human ascending thoracic AAD tissues. CONCLUSIONS: Our study reveals the dynamic epigenetic induction of SMC phenotypic alterations in AAD. DNA damage and cytosolic leakage drive SMCs from a contractile phenotype to an inflammatory phenotype.

The Psychology of Kink: A Cross-Sectional Survey Investigating the Association Between Adult Attachment Style and BDSM-Related Identity Choice in China.

BDSM is a type of sexual preference that includes bondage and discipline, dominance and submission, and sadism and masochism. Research has identified three specific power exchange roles in the practice of BDSM: dominance, submission, and switch. It has also been suggested that attachment style potentially influences BDSM interests. This study investigated the potential roles of attachment style in driving BDSM identity. A questionnaire was completed by a cross-sectional Chinese sample (n = 3310, age range 18-30 years), including 1856 BDSM practitioners (436 men, 1420 women). To assess attachment style, the questionnaire included a Chinese translation of the Adult Attachment Scale as well as items surveying BDSM interests. Compared to non-BDSM practitioners, attachment styles were not significantly different from BDSM practitioners. However, practitioners with different BDSM identities showed a significant difference in their attachment styles. Secure and avoidant attachment styles were associated with dominance, whereas submissiveness recorded high average scores of separation anxiety in both males and females. BDSM identities based on gender revealed that 60.5% of female practitioners assumed the role of submissiveness and this group recorded the highest average scores of separation anxiety among all groups. These results show that BDSM identity is related to attachment style. However, the results did not support the hypothesis that attachment styles potentially drive BDSM identities. Further research is needed to explore other psychological processes that drive BDSM identities in order to provide guidance for BDSM practitioners in choosing suitable identities, thereby helping practitioners to choose suitable identity partners and avoid negative experiences during BDSM participation.

Weizmannia coagulans JA845 improves atherosclerosis induced by vitamin D3 and high-fat diet in rats through modulating lipid metabolism, oxidative stress, and endothelial vascular injury.

AIMS: Probiotics have been proved to be strongly linked to the occurrence and progression of atherosclerosis. This study aimed to investigate the improved effects and mechanisms underlying a potential probiotic, Weizmannia coagulans JA845, on atherosclerosis. METHODS AND RESULTS: Male Sprague-Dawley rats supported on a high-fat diet with vitamin D3 supplementation were subjected to W. coagulans JA845 treatment. W. coagulans JA845 obviously alleviated histological abnormalities of the abdominal aorta. After 6 weeks of W. coagulans JA845 administration, levels of TG, TC, LDL, ox-LDL, ROS, and MDA in the JA845 group decreased significantly, and those of HDL, GSH-Px, and SOD were markedly elevated. Treatment with W. coagulans JA845 also inhibited the secretion of ICAM-1 and VCAM-1 and regulated the plasma NO and eNOS content. In brief, administration of W. coagulans JA845 promoted the expression of the SIRT3/SOD2/FOXO3A pathway, inhibited the lipid metabolism pathway, SREBP-1c/FAS/DGAT2, and suppressed the JNK2/P38 MAPK/VEGF pathway implicated in endothelial injury. CONCLUSIONS: These results indicated W. coagulans JA845 improved atherosclerosis by regulating lipid metabolism, antioxidative stress, and protecting against endothelial injury.

Transformation of Ginsenosides by Lactiplantibacillus plantarum MB11 Fermentation: Minor Ginsenosides Conversion and Enhancement of Anti-Colorectal Cancer Activity.

The present study aimed to increase the content of minor ginsenosides and enhance the anti-colorectal cancer activity of ginsenosides via biotransformation by Lactiplantibacillus plantarum MB11 screened from fermented foods. A subcutaneous transplantation tumor model of murine colorectal cancer CT26 cells was established in mice to study the anticarcinogenic activities and mechanism of fermented total ginsenosides (FTGs). The results showed that L. plantarum MB11 fermentation increased the content of minor ginsenosides and decreased that of major ginsenosides. FTGs reduced the tumor weight and size compared with the model group. Immunofluorescence and TdT-mediated dUTP nick end labeling (TUNEL) analysis showed that FTGs significantly increase the number of caspase-3 cells in tumor tissue and induce cell apoptosis. Mechanically, FTGs activate AMPK/mTOR autophagy pathway and regulate JAK2/STAT3 and Bax/Bcl-2/caspase-3 apoptosis pathway. Overall, fermentation with L. plantarum MB11 enhanced minor ginsenosides in total ginsenosides, and FTGs induced subcutaneous transplantation tumor autophagy and apoptosis in mice.

Lactiplantibacillus plantarum HG20 attenuates II type collagen-induced rheumatoid arthritis in rats via anti-inflammatory and inhibition of apoptosis.

AIMS: This study aimed to explore the therapeutic effects of Lactiplantibacillus plantarum HG20 (HG20) on collagen-induced arthritis (CIA) rats and its mechanism. METHODS AND RESULTS: CIA rats were established by injecting bovine type II collagen for 7 days, and treated by intragastric administration HG20 for 21 days. The foot palm temperature and arthritis score were measured once a week. The pathological changes in the knee joint were observed by hematoxylin and eosin staining. The levels of cytokines were detected by enzyme linked immunosorbent assay, and the effects of HG20 on inflammatory and apoptosis pathway of spleen cells were detected by western blot analysis. The results indicated that HG20 reduced the joint swelling degree and foot palm temperature, inhibited the development of joint histopathology, decreased the levels of pro-inflammatory cytokines, down-regulate the expression of pro-inflammatory cytokines by nuclear factor kappa-B pathway, and inhibited the apoptosis of spleen cells by inhibiting phosphatidylinositol 3-kinase/protein kinase B pathway and regulating apoptosis pathways. CONCLUSIONS: HG20 had an adjuvant therapeutic effect on arthritis in CIA rats, and its mechanism might be related to the inflammatory and apoptosis pathway. SIGNIFICANCE AND IMPACT OF STUDY: These results revealed that HG20 could be used as a functional probiotic in the field of food and medical, and which played a potential role in the prevention and treatment of arthritis.

Lactobacillus plantarum DP189 prevents cognitive dysfunction in D-galactose/AlCl3 induced mouse model of Alzheimer's disease via modulating gut microbiota and PI3K/Akt/GSK-3ß signaling pathway.

Probiotic intervention has beneficial effects on host brain function and behavior via regulating microbiota-gut-brain axis; however, the underlying mechanism is not yet understood. Herein, we investigated that the effects of Lactobacillus plantarum DP189 (DP189) administration in preventing cognitive dysfunction and pathology of Alzheimer's disease (AD) in D-galactose (D-gal) and AlCl3-induced AD model mice. After L. plantarum DP189 intervention for 10 weeks, we assessed cognitive behavior, neurotransmitter expression, histological changes, microbial communities, and the mechanisms underlying the disease in AD model mice. The results showed that L. plantarum DP189 intervention prevented cognitive dysfunction by behavioral test. Increased levels of serotonin, dopamine, and gamma-aminobutyric acid positively affected the pathological processes by ameliorating neuronal damage, beta-amyloid deposition, and tau pathology. L. plantarum DP189 intervention simultaneously modulated the gut microbial communities to alleviate gut dysbiosis. Moreover, L. plantarum DP189 inhibited tau hyperphosphorylation by regulating the PI3 K/Akt/GSK-3ß pathway. These findings indicated that L. plantarum DP189 intervention is a promising therapeutic strategy to prevent the onset and development of AD.

Excimer laser atherectomy combined with drug-coated balloon versus drug-eluting balloon angioplasty for the treatment of infrapopliteal arterial revascularization in ischemic diabetic foot: 24-month outcomes.

There are few studies on excimer laser (308 nm) atherectomy in the treatment of infrapopliteal artery disease. The purpose of this retrospective clinical study was to assess the efficacy and safety of excimer laser atherectomy (ELA) in combination with adjuvant drug-coated balloon angioplasty (DCB) compared to DCB for infrapopliteal arterial revascularization in patients with ischemic diabetic foot. From September 2018 to February 2019, a total of 79 patients with diabetic foot were treated for infrapopliteal arterial revascularization at Tianjin First Central Hospital (Tianjin, China). In this project, 35 patients were treated with ELA combined with DCB angioplasty, and 44 patients were treated with DCB angioplasty. The patients' baseline characteristics were similar between the 2 groups. The primary efficacy endpoints through 24 months were clinically driven target lesion revascularization (CD-TLR), wound healing rate, major amputation rate, and target vessel patency rate. The primary safety endpoint through 24 months was all-cause mortality. The primary efficacy results at 24 months of ELA + DCB versus DCB were CD-TLR of 14.3% versus 34.1% (p = 0.044), wound healing rate of 88.6% versus 65.9% (p = 0.019), target vessel patency rate of 80.0% versus 52.3% (p = 0.010), and major amputations rate of 5.7% versus 22.7% (p = 0.036). The safety signal at 24 months of all-cause mortality rate was 2.9% for ELA + DCB group and 4.5% for DCB group (p = 0.957). ELA combined with DCB angioplasty is more effective than DCB in the treatment of infrapopliteal artery disease in patients with ischemic diabetic foot, which can improve the wound healing rate and target vessel patency rate. There was no statistical difference in the safety results between the two groups.

Rethinking Power Efficiency for Next-Generation Processor-Free Sensing Devices.

The last decade has seen significant advances in power optimization for IoT sensors. The conventional wisdom considers that if we reduce the power consumption of each component (e.g., processor, radio) into µW-level of power, the IoT sensors could achieve overall ultra-low power consumption. However, we show that this conventional wisdom is overturned, as bus communication can take significant power for exchanging data between each component. In this paper, we analyze the power efficiency of bus communication and ask whether it is possible to reduce the power consumption for bus communication. We observe that existing bus architectures in mainstream IoT devices can be classified into either push-pull or open-drain architecture. push-pull only adapts to unidirectional communication, whereas open-drain inherently fits for bidirectional communication which benefits simplifying bus topology and reducing hardware costs. However, open-drain consumes more power than push-pull due to the high leakage current consumption while communicating on the bus. We present Turbo, a novel approach introducing low power to the open-drain based buses by reducing the leakage current created on the bus. We instantiate Turbo on I2C bus and evaluate it with commercial off-the-shelf (COTS) sensors. The results show a 76.9% improvement in power efficiency in I2C communication.

A Theoretical Comparative Study of Vapor-Compression Refrigeration Cycle using Al2O3 Nanoparticle with Low-GWP Refrigerants.

Nanorefrigerant is a mixture of nanoparticles and pure refrigerant, which can increase heat transfer characteristics in refrigeration and air conditioning equipment. The performance of four different Al2O3 nanorefrigerants and their pure fluids (R600a, R134a, R1234yf, and R1233zd(E)) is analyzed in a vapor-compression refrigeration cycle. The enthalpy of a nanorefrigerant in the refrigeration cycle is calculated by using the prediction method based on the density of nanorefrigerant. A numerical model is established for the thermodynamic analysis, and the results show that adding nanoparticles to the pure refrigerant enhances heat transfer in heat exchangers, increases cooling capacity, reduces compressor power consumption, and finally improves the performance of the refrigeration system. The COP improvement of R1233zd(E) + Al2O3 nanorefrigerant is the highest, and the COP improvement of R134a + Al2O3 and R1234yf + Al2O3 are close to each other. When the mass fraction of Al2O3 nanoparticles increases to 0.30%, the COP of R1233zd(E) and R600a increases by more than 20%; the maximum exergy efficiency is 38.46% for R1233zd(E) + Al2O3, and the minimum exergy efficiency is 27.06% for pure R1234yf. The results provide a basis for the application of nanorefrigerants in the vapor compression refrigeration cycle.

The independent risks and specific biomarker of breast cancer-related ischemic stroke.

AIM: This retrospective study was designed to investigate the independent risks and specific biomarker for breast cancer-related ischemic stroke (BCRS). METHODS: Clinical features and laboratory findings were compared between BCRS group and breast cancer group without stroke, and further multivariate analyses were performed to predict independent risks factors for BCRS patients. A receiver operator characteristic (ROC) curve analysis was configured to estimate the diagnostic efficacy of each independent risk and the product of these risks and to obtain the optimal cut-off value of diagnosis, which was termed the BCRS Index. RESULTS: BCRS patients had elevated plasma D-dimer and CA153 levels and platelet-to-lymphocyte ratio (PLR), as well as more patients received endocrine therapy (all p ＜ 0.05). Moreover, multivariate analysis revealed that D-dimer levels (odds ratio [OR]: 1.002; 95% confidence interval [CI]: 1.001-1.003; p = 0.000), CA153 levels (OR: 1.005; 95% CI: 1.001-1.008; p = 0.007), PLR (OR: 1.010; 95% CI: 1.004-1.015; p = 0.001), and endocrine therapy (OR: 1.268; 95% CI: 1.087-1.479; p = 0.003) were identified as independent risks of BCRS. Furthermore, ROC analysis displayed that the product of risks had the best diagnostic efficacy, of which the area under the curve was 0.846 ± 0.28. The optimum cut-off point was 2.37 × 106/mL, which was termed the BCRS Index with higher diagnostic accuracy and validity. CONCLUSIONS: Endocrine therapy, as well as elevated plasma D-dimer and CA153 levels and PLR values may be independent risks for BCRS. Furthermore, BCRS Index should be served as a novel specific biomarker for BCRS, which is useful to distinguish BCRS for clinicians.

Visible-light-enabled aerobic oxidative Csp3-H functionalization of glycine derivatives using an organic photocatalyst: access to substituted quinoline-2-carboxylates.

A practical visible-light-induced aerobic oxidative dehydrogenative coupling reaction of glycine derivatives with olefins has been developed to efficiently synthesize quinoline-2-carboxylates. This metal-free process proceeds smoothly under mild conditions and exhibits good tolerance of functional groups. Given the low cost of the catalyst and feedstock materials, the mild reaction conditions and the absence of hazardous byproducts, this protocol should find broad applications in the synthesis of quinoline-2-carboxylate derivatives.

Lactobacillus plantarum NA136 ameliorates nonalcoholic fatty liver disease by modulating gut microbiota, improving intestinal barrier integrity, and attenuating inflammation.

Gut microbiota dysbiosis, associated with insulin resistance, weak intestinal barrier integrity, and inflammation, may also play a role in the development of dietary-induced nonalcoholic fatty liver disease (NAFLD). This study investigates the effects of dietary Lactobacillus plantarum NA136 administration on gut microbiota composition in an insulin-resistant C57BL/6J mouse NAFLD model. Comparison of mice with and without L. plantarum NA136 treatment revealed that L. plantarum NA136 treatment not only relieved insulin resistance but also significantly increased relative proportions of Desulfovibrio, Alistipes, Prevotella, and Enterorhabdus in gut microbiota of NAFLD mice. Meanwhile, L. plantarum NA136 administration also inhibited pathogenic bacterial growth, while promoting growth of probiotics such as Allobaculum, Lactobacillus, and, most markedly, Bifidobacterium. Moreover, L. plantarum NA136 treatment of NAFLD mice improved intestinal barrier integrity and attenuated high-fat and fructose diet (HFD/F)-induced inflammation. These results implicate gut-liver-axis-dependent microbiota modulation as the underlying mechanism for L. plantarum NA136-induced amelioration of NAFLD.Key points• L. plantarum NA136 corrects gut microbiota disorders caused by a high-fat and fructose diet. • L. plantarum NA136 strengthens the intestinal barrier and reduces inflammation in the liver. • L. plantarum NA136 relieves NAFLD by improving the gut-liver axis.

Profiling of the Risk Factors and Designing of a Model to Identify Ischemic Stroke in Patients with Non-Hodgkin Lymphoma: A Multicenter Retrospective Study.

BACKGROUND: The occurrence of ischemic stroke in patients with non-Hodgkin lymphoma (NHL) is not well understood. This study aimed to determine independent risk factors to identity ischemic stroke in non-Hodgkin lymphoma-associated ischemic stroke (NHLAIS) patients. METHODS: This retrospective study was conducted on NHLAIS patients and age- and gender-matched NHL patients. We collected clinical data of patients in both groups and used multiple logistic regression analysis to identify independent risk factors for NHLAIS. A receiver operating characteristic (ROC) analysis was used to establish an identification model based on potential risk factors of NHLAIS. RESULTS: Sixty-three NHLAIS patients and 63 NHL patients were enrolled. Stage III/IV (58/63, 92.1%) and multiple arterial infarcts (44/63, 69.8%) were common among NHLAIS patients. Notably, NHLAIS patients had higher levels of serum fibrinogen (FIB), D-dimer, and ferritin (SF) and prolonged thromboplastin time and prothrombin time (PT) compared with NHL patients (all p < 0.05). Elevated FIB, D-dimer, and SF and prolonged PT were independent risk factors for NHLAIS. The area under the ROC curve of the identification model of NHLAIS patients was largest compared to that of other risk factors (0.838, 95% confidence interval: 0.759-0.899) (p < 0.05). CONCLUSION: This study reveals that elevated serum FIB, D-dimer, and SF and prolonged PT are potential independent risk factors of NHLAIS. The identification model established in this study may help monitor NHL patients who are at high risk of developing NHLAIS.

A partial encryption algorithm for medical images based on quick response code and reversible data hiding technology.

BACKGROUND: Medical image data, like most patient information, have a strong requirement for privacy and confidentiality. This makes transmitting medical image data, within an open network, problematic, due to the aforementioned issues, along with the dangers of data/information leakage. Possible solutions in the past have included the utilization of information-hiding and image-encryption technologies; however, these methods can cause difficulties when attempting to recover the original images. METHODS: In this work, we developed an algorithm for protecting medical image key regions. Coefficient of variation is first employed to identify key regions, a.k.a. image lesion areas; then additional areas are processed as blocks and texture complexity is analyzed. Next, our novel reversible data-hiding algorithm embeds lesion area contents into a high-texture area, after which an Arnold transformation is utilized to protect the original lesion information. After this, we use image basic information ciphertext and decryption parameters to generate a quick response (QR) code used in place of original key regions. RESULTS: The approach presented here allows for the storage (and sending) of medical image data within open network environments, while ensuring only authorized personnel are able to recover sensitive patient information (both image and meta-data) without information loss. DISCUSSION: Peak signal to noise ratio and the Structural Similarity Index measures show that the algorithm presented in this work can encrypt and restore original images without information loss. Moreover, by adjusting the threshold and the Mean Squared Error, we can control the overall quality of the image: the higher the threshold, the better the quality and vice versa. This allows the encryptor to control the amount of degradation as, at appropriate amounts, degradation aids in the protection of the image. CONCLUSIONS: As shown in the experimental results, the proposed method allows for (a) the safe transmission and storage of medical image data, (b) the full recovery (no information loss) of sensitive regions within the medical image following encryption, and (c) meta-data about the patient and image to be stored within and recovered from the public image.

Development of a support vector machine learning and smart phone Internet of Things-based architecture for real-time sleep apnea diagnosis.

BACKGROUND: The breathing disorder obstructive sleep apnea syndrome (OSAS) only occurs while asleep. While polysomnography (PSG) represents the premiere standard for diagnosing OSAS, it is quite costly, complicated to use, and carries a significant delay between testing and diagnosis. METHODS: This work describes a novel architecture and algorithm designed to efficiently diagnose OSAS via the use of smart phones. In our algorithm, features are extracted from the data, specifically blood oxygen saturation as represented by SpO2. These features are used by a support vector machine (SVM) based strategy to create a classification model. The resultant SVM classification model can then be employed to diagnose OSAS. To allow remote diagnosis, we have combined a simple monitoring system with our algorithm. The system allows physiological data to be obtained from a smart phone, the data to be uploaded to the cloud for processing, and finally population of a diagnostic report sent back to the smart phone in real-time. RESULTS: Our initial evaluation of this algorithm utilizing actual patient data finds its sensitivity, accuracy, and specificity to be 87.6%, 90.2%, and 94.1%, respectively. DISCUSSION: Our architecture can monitor human physiological readings in real time and give early warning of abnormal physiological parameters. Moreover, after our evaluation, we find 5G technology offers higher bandwidth with lower delays ensuring more effective monitoring. In addition, we evaluate our algorithm utilizing real-world data; the proposed approach has high accuracy, sensitivity, and specific, demonstrating that our approach is very promising. CONCLUSIONS: Experimental results on the apnea data in University College Dublin (UCD) Database have proven the efficiency and effectiveness of our methodology. This work is a pilot project and still under development. There is no clinical validation and no support. In addition, the Internet of Things (IoT) architecture enables real-time monitoring of human physiological parameters, combined with diagnostic algorithms to provide early warning of abnormal data.

Lactobacillus plantarum C88 protects against aflatoxin B1-induced liver injury in mice via inhibition of NF-κB-mediated inflammatory responses and excessive apoptosis.

BACKGROUND: Probiotics play an important role in the human and animal defense against liver damage. However, the protective mechanism of Lactobacillus plantarum C88 on chronic liver injury induced by mycotoxin remains unclear. RESULTS: In this study, the addition of L. plantarum C88 obviously ameliorated the increased contents of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total cholesterol and triglyceride, the diminish contents of total protein and albumin in serum of mice challenged with AFB1. Simultaneously, L. plantarum C88 attenuated the inflammatory response via significantly reducing the levels of pro-inflammatory factors, including interleukin-1ß (IL-1ß), IL-6, IL-8, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) in serum. Furthermore, L. plantarum C88 remarkably down-regulated the nuclear factor kappa B (NF-κB) signaling pathways by weakening the expression of toll-like receptor 2 (TLR2) and TLR4, and inhibited NF-κB nuclear translocation through enhancing the expression of NF-κB inhibitor (IκB). Neutralization experiments confirmed that L. plantarum C88 decreased the levels of some pro-inflammatory factors due to the suppression of the NF-κB signaling pathways. Besides, L. plantarum C88 decreased the levels of Bax and Caspase-3, elevated the level of Bcl-2, and reduced mRNA expressions of Fatty acid synthetase receptor (Fas), FAS-associated death domain (FADD), TNF receptor associated death domain (TRADD) and Caspase-8 in the liver. CONCLUSIONS: Probiotic L. plantarum C88 prevented AFB1-induced secretion of pro-inflammatory cytokines by modulating TLR2/NF-κB and TLR4/NF-κB pathways. The molecular mechanisms of L. plantarum C88 in ameliorating AFB1-induced excessive apoptosis included regulating the mitochondrial pathway and cell death receptor pathways.

Lactobacillus plantarum NA136 improves the non-alcoholic fatty liver disease by modulating the AMPK/Nrf2 pathway.

Hepatic lipid metabolic disorders and oxidative stress are involved in the development of non-alcoholic fatty liver disease (NAFLD). This study is to determine the protective effects of Lactobacillus plantarum NA136 on high-fat diet and fructose (HFD/F)-induced NAFLD and to elucidate its underlying molecular mechanisms. Male C57BL/6J mice had been fed with normal diet (ND), HFD/F, or HFD/F supplemented with L. plantarum NA136 for 16 weeks. Treatment with L. plantarum NA136 significantly lowered the body weight gain and decreased the mass of fat tissues, lipids, AST, and ALT levels of HFD/F-treated mice. Our results showed that L. plantarum NA136 activated AMPK pathway to phosphorylate ACC and to suppress the SREBP-1/FAS signaling to inhibit the de novo lipogenesis and increase the fatty acid oxidation. Furthermore, with treatment of L. plantarum NA136, the nuclear translocation of NF-E2-related factor 2 (Nrf2) was also increased which could activate antioxidant pathway. These findings suggested that L. plantarum NA136 improved NAFLD by regulating the fatty acid metabolism and defending against oxidative stress through AMPK and Nrf2 pathways, respectively.

Using an artificial neural network to map cancer common data elements to the biomedical research integrated domain group model in a semi-automated manner.

BACKGROUND: The medical community uses a variety of data standards for both clinical and research reporting needs. ISO 11179 Common Data Elements (CDEs) represent one such standard that provides robust data point definitions. Another standard is the Biomedical Research Integrated Domain Group (BRIDG) model, which is a domain analysis model that provides a contextual framework for biomedical and clinical research data. Mapping the CDEs to the BRIDG model is important; in particular, it can facilitate mapping the CDEs to other standards. Unfortunately, manual mapping, which is the current method for creating the CDE mappings, is error-prone and time-consuming; this creates a significant barrier for researchers who utilize CDEs. METHODS: In this work, we developed a semi-automated algorithm to map CDEs to likely BRIDG classes. First, we extended and improved our previously developed artificial neural network (ANN) alignment algorithm. We then used a collection of 1284 CDEs with robust mappings to BRIDG classes as the gold standard to train and obtain the appropriate weights of six attributes in CDEs. Afterward, we calculated the similarity between a CDE and each BRIDG class. Finally, the algorithm produces a list of candidate BRIDG classes to which the CDE of interest may belong. RESULTS: For CDEs semantically similar to those used in training, a match rate of over 90% was achieved. For those partially similar, a match rate of 80% was obtained and for those with drastically different semantics, a match rate of up to 70% was achieved. DISCUSSION: Our semi-automated mapping process reduces the burden of domain experts. The weights are all significant in six attributes. Experimental results indicate that the availability of training data is more important than the semantic similarity of the testing data to the training data. We address the overfitting problem by selecting CDEs randomly and adjusting the ratio of training and verification samples. CONCLUSIONS: Experimental results on real-world use cases have proven the effectiveness and efficiency of our proposed methodology in mapping CDEs with BRIDG classes, both those CDEs seen before as well as new, unseen CDEs. In addition, it reduces the mapping burden and improves the mapping quality.

A semantics-oriented computational approach to investigate microRNA regulation on glucocorticoid resistance in pediatric acute lymphoblastic leukemia.

BACKGROUND: Acute lymphoblastic leukemia is the most prevalent neoplasia among children. Despite the tremendous achievements of state-of-the-art treatment strategies, drug resistance is still a major cause of chemotherapy failure leading to relapse in pediatric acute lymphoblastic leukemia. The underlying mechanisms of such phenomenon are not yet clear and subject to further exploration. Prior research has shown that microRNAs can act as post-transcriptional regulators of many genes related to drug resistance. However, details of microRNA regulation mechanisms in pediatric acute lymphoblastic leukemia are far from completely understood. METHODS: We utilized a computational approach based upon emerging biomedical and biological ontologies and semantic technologies to investigate the important roles of microRNA: mRNA regulation on glucocorticoid resistance in pediatric acute lymphoblastic leukemia. In particular, various filtering mechanisms were designed based on the user-provided MeSH term to narrow down the most promising microRNAs in an effective manner. RESULTS: During our manual search on background literature, we found a total of 18 candidate microRNAs that possibly regulate glucocorticoid resistance in pediatric acute lymphoblastic leukemia. After the first-round filtering using the Broader-Match option where both the user-provided MeSH term and its direct parent term were utilized, the number of targets for 18 microRNAs was reduced from 232 to 74. During the second-round filtering with the Exact-Match option where only the MeSH term itself was utilized, the number of targets was further reduced to 19. Finally, we conducted semantic searches in the OmniSearch software tool on the five likely regulating microRNAs and identified two most likely microRNAs. CONCLUSIONS: We successfully identified two microRNAs, hsa-miR-142-3p and hsa-miR-17-5p, which are computationally predicted to closely relate to glucocorticoid resistance, thus potentially serving as novel biomarkers and therapeutic targets in pediatric acute lymphoblastic leukemia.