Machine Learning-Based Technique for the Severity Classification of Sublingual Varices according to Traditional Chinese Medicine.

Tongue diagnosis, a noninvasive examination, is an essential step for syndrome differentiation and treatment in traditional Chinese medicine (TCM). Sublingual vein (SV) is examined to determine the presence of blood stasis and blood stasis syndrome. Many studies have shown that the degree of SV stasis positively correlates with disease severity. However, the diagnoses of SV examination are often subjective because they are influenced by factors such as physicians' experience and color perception, resulting in different interpretations. Therefore, objective and scientific diagnostic approaches are required to determine the severity of sublingual varices. This study aims at developing a computer-assisted system based on machine learning (ML) techniques for diagnosing the severity of sublingual varicose veins. We conducted a comparative study of the performance of several supervised ML models, including the support vendor machine, K-neighbor, decision tree, linear regression, and Ridge classifier and their variants. The main task was to differentiate sublingual varices into mild and severe by using images of patients' SVs. To improve diagnostic accuracy and to accelerate the training process, we proposed using two model reduction techniques, namely, the principal component analysis in conjunction with the slice inverse regression and the convolution neural network (CNN), to extract valuable features during the preprocessing of data. Our results showed that these two extraction methods can reduce the training time for the ML methods, and the Ridge-CNN method can achieve an accuracy rate as high as 87.5%, which is similar to that of experienced TCM physicians. This computer-aided tool can be used for reference clinical diagnosis. Furthermore, it can be employed by junior physicians to learn and to use in clinical settings.

Synergistic effects and antityrosinase mechanism of four plant polyphenols from Morus and Hulless Barley.

Sanggenone C, oxyresveratrol, catechin and l-epicatechin exist in Morus and Hulless Barley as natural polyphenols with antityrosinase activity. Little research on their synergistic and structure-function relationships of them has been reported in recent years. In this paper, the inhibition mechanisms of these four plant polyphenols were investigated by enzyme kinetics, HPLC, fluorescence spectra, and molecular docking methods. The results showed that oxyresveratrol (IC50 = 1.096 ± 0.048 µg/mL), sanggenone C (IC50 = 13.360 ± 1.029 µg/mL), l-epicatechin (IC50 = 55.730 ± 1.762 µg/mL), and catechin (IC50 = 148.500 ± 3.355 µg/mL) exhibited tyrosinase inhibition activity. When sangenone C (14 µg/mL) was mixed with l-epicatechin (56 µg/mL) at 4:1 (40 µL + 10 µL), the highest tyrosinase inhibition was achieved. Molecular docking showed that the number and position of phenolic hydroxyls of polyphenols were the key for tyrosinase inhibition activity. This study provided new ideas for the application of these four plant polyphenols from Hulless Barley and Morus as tyrosinase inhibitors in food preservation.

Discovery of Hyperstable Noncanonical Plant-Derived Epidermal Growth Factor Receptor Agonist and Analogs.

Here, we report the discovery of the first plant-derived and noncanonical epidermal growth factor receptor (EGFR) agonist, the 36-residue bleogen pB1 from Pereskia bleo of the Cactaceae family. We show that bleogen pB1 is a low-affinity EGFR agonist using a suite of chemical, biochemical, cellular, and animal experiments which include incisor eruption and wound-healing mouse models. A focused positional scanning pB1 library of Ala- and d-amino acid scans yielded a high-affinity pB1 analog, [K29k]pB1, with a 60-fold-improved EGFR affinity and mitogenicity. We show that the potency of [K29k]pB1 and the epidermal growth factor (EGF) is comparable in a diabetic mouse wound-healing model. We also show that both bleogen pB1 and [K29k]pB1 are hyperstable, being >100-fold more stable than EGF against proteolytic degradation. Overall, our discovery of a noncanonical proteolytic-resistant EGFR agonist scaffold could open new avenues for developing wound healing and skin regeneration therapeutics and biomaterials.

Using Social Media to Enhance Provider Network for HIV and Harm Reduction Service Integration in Vietnam.

Social media can potentially serve as a platform to coordinate medical care among fragmented health sectors. This paper describes procedures of using social media to enhance antiretroviral therapy (ART) and methadone maintenance treatment (MMT) providers' virtual network for integrated service for HIV-positive people who inject drugs (PWID) in Vietnam. A total of 88 ART and MMT treatment providers participated in person group sessions followed by online virtual support to improve service integration. In-person reunions were held to reinforce Facebook participation and network activities. Content analysis was used to identify keywords and topic categories of the online information exchange. Both MMT and ART providers were actively engaged in online communications. Referral and treatment adherence were the two most frequently discussed topic areas by both the MMT and ART providers. Frequent cross-agency connections were observed. Online provider networks and communities could be built and useful to support treatment providers to improve service integration.

Selenium-isotopic signature toward mass spectrometric identification and enzyme activity assay.

The unraveling of enzymatic reactions, especially identification of enzymatic substrates or products, is important to elucidate biological processes. Here a selenium-isotopic signature for mass spectrometric identification of enzymatic-related species is demonstrated by using selenium-containing peptides (SePeps) as substrates. Thus a strategy is proposed for rapid and precise assay of multiple enzyme activity. These SePeps can be synthesized by introduction of one selenomethionine residue in the sequence and simply identified in the full-scan mode with the feature of distinctive selenium-isotopic distribution without MS/MS verifications, which proposes a novel solution to the specific identification of enzyme-related species, allows to exclude the interferences of species with tiny mass differences in bio-samples, and meanwhile can offer a judgement on data accuracy for the analysis of enzyme activities. As a proof-of-concept, a method for multiple analysis of two representative enzymes in MCF-7 cell lysate has been developed with the isotopic peak areas of either SePep substrates or enzymatic products with the top intensities. These results could be the foundation to extend the method for more complicated enzyme systems. The selenium-isotopic signature provides a powerful protocol for high-throughput assays of peptide-metabolizing enzymes with enhanced confidence and can be extended to screen enzymatic reaction-related substrates.

Transcriptome Profiling of Wheat Inflorescence Development from Spikelet Initiation to Floral Patterning Identified Stage-Specific Regulatory Genes.

Early reproductive development in cereals is crucial for final grain number per spike and hence the yield potential of the crop. To date, however, no systematic analyses of gene expression profiles during this important process have been conducted for common wheat (Triticum aestivum). Here, we studied the transcriptome profiles at four stages of early wheat reproductive development, from spikelet initiation to floral organ differentiation. K-means clustering and stage-specific transcript identification detected dynamically expressed homeologs of important transcription regulators in spikelet and floral meristems that may be involved in spikelet initiation, floret meristem specification, and floral organ patterning, as inferred from their homologs in model plants. Small RNA transcriptome sequencing discovered key microRNAs that were differentially expressed during wheat inflorescence development alongside their target genes, suggesting that miRNA-mediated regulatory mechanisms for floral development may be conserved in cereals and Arabidopsis. Our analysis was further substantiated by the functional characterization of the ARGONAUTE1d (AGO1d) gene, which was initially expressed in stamen primordia and later in the tapetum during anther maturation. In agreement with its stage-specific expression pattern, the loss of function of the predominantly expressed B homeolog of AGO1d in a tetraploid durum wheat mutant resulted in smaller anthers with more infertile pollens than the wild type and a reduced grain number per spike. Together, our work provides a first glimpse of the gene regulatory networks in wheat inflorescence development that may be pivotal for floral and grain development, highlighting potential targets for genetic manipulation to improve future wheat yields.

L-3-n-butylphthalide reduces tau phosphorylation and improves cognitive deficits in AßPP/PS1-Alzheimer's transgenic mice.

L-3-n-butylphthalide (L-NBP), an extract from seeds of Apium graveolens Linn (Chinese celery), has been shown to have neuroprotective effects on cerebral ischemic, vascular dementia and amyloid-ß (Aß)-induced animal models by inhibiting oxidative injury, neuronal apoptosis and glial activation, regulating amyloid-ß protein precursor (AßPP) processing and reducing Aß generation. The aim of the present study was to examine the effect of L-NBP on learning and memory in AßPP and presenilin 1 (PS1) double-transgenic AD mouse model (AßPP/PS1) and the mechanisms of L-NBP in reducing Aß accumulation and tau phosphorylation. Twelve-month old AßPP/PS1 mice were given 15 mg/kg L-NBP by oral gavage for 3 months. L-NBP treatment significantly improved the spatial learning and memory deficits compared to the vehicle-treated AßPP/PS1 mice, whereas L-NBP treatment had no effect on cerebral Aß plaque deposition and Aß levels in brain homogenates. However, we found an L-NBP-induced reduction of tau hyperphosphorylation at Ser199, Thr205, Ser396, and Ser404 sites in AßPP/PS1 mice. Additionally, the expressions of cyclin-dependent kinase and glycogen synthase kinase 3ß, the most important kinases involved in tau phosphorylation, were markedly decreased by L-NBP treatment. The effects of L-NBP on decreasing tau phosphorylation and kinases activations were further confirmed in neuroblastoma SK-N-SH cells overexpressing wild-type human AßPP695 (SK-N-SH AßPPwt). L-NBP shows promising candidate of multi-target neuronal protective agent for the treatment of Alzheimer's disease.

L-3-n-butylphthalide regulates amyloid precursor protein processing by PKC and MAPK pathways in SK-N-SH cells over-expressing wild type human APP695.

Amyloid precursor protein (APP) is cleaved by α-secretase, within the amyloid-ß (Aß) sequence, resulting in the release of a secreted fragment (αAPPs) and precluding Aß production. We investigated the effects of a promising anti-AD new drug, l-3-n-butylphthalide (L-NBP), on APP processing and Aß generation in neuroblastoma SK-N-SH cells overexpressing wild-type human APP695. L-NBP significantly increased αAPPs release, and reduced Aß generation. The steady-state full-length APP levels were unaffected by L-NBP. It suggested that L-NBP regulated APP processing towards to the non-amyloidogenic α-secretase pathway. Protein kinase C (PKC) and mitogen activated protein (MAP) kinase might be involved in L-NBP-induced αAPPs secretion. L-NBP significantly increased PKCα and ɛ activations, lowered PKCγ activation and increased the phosphorylation of p44/p42 MAPK. Furthermore, PKC and MAPK inhibitors partially reduced L-NBP-induced αAPPs secretion. The results suggested alternative pharmacological mechanisms of L-NBP regarding the treatment of Alzheimer's disease (AD).

Second-hand smoke and chronic bronchitis in Taiwanese women: a health-care based study.

BACKGROUND: Cigarette smoking cannot fully explain the epidemiologic characteristics of chronic obstructive pulmonary disease (COPD) in women, particularly for those who rarely smoke, but COPD risk is not less than men. The aim of our study is to investigate the relationship between second-hand smoke (SHS) exposure and chronic bronchitis in Taiwanese women. METHODS: We used Taiwan's National Health Insurance Bureau claims data in 1999, and cross-checked using criteria set by the American Thoracic Society; there were 33 women with chronic bronchitis, 182 with probable chronic bronchitis, and 205 with no chronic bronchitis during our interview time between 2000 and 2005. We measured second-hand smoke (SHS) exposure by self-reported measures (household users and duration of exposure), and validated this by measuring urinary cotinine levels of a subset subjects. Classification of chronic bronchitis was also based on spirometry defined according to the GOLD guidelines to get the severity of COPD. RESULTS: Women who smoked and women who had been exposed to a lifetime of SHS were 24.81-fold (95% CI: 5.78-106.38) and 3.65-fold (95% CI: 1.19-11.26) more likely to have chronic bronchitis, respectively, than those who had not been exposed to SHS. In addition, there was a significant increasing trend between the severity of COPD and exposure years of SHS (p < 0.01). The population attributable risk percentages of chronic bronchitis for smokers and those exposed to SHS were 23.2 and 47.3% respectively. CONCLUSIONS: These findings indicate that, besides cigarette smoking, exposure to SHS is a major risk factor for chronic bronchitis in Taiwanese women.

Vasodilator constituents from the roots of Lysidice rhodostega.

Two new phloroglucinol glycosides, lysidisides A and B, and two new flavanol ramifycations, lysidicichin and mopanolside, together with (+)-mopanol, polydatin and E-resveratrol 3-O-beta-D-xylopyranoside were isolated from the EtOAc extract of the roots of Lysidice rhodostega. The structures of the new compounds were elucidated on the basis of chemical and spectral evidence. Lysidisides A and B, (+)-mopanol and polydatin inhibited phenylepherine (Phe)-induced vasoconstriction in the rat aortic rings in the presences of indomethacin (Indo) and Nomega-L-nitroarginine (L-NA).

[Effect of mild and moderate excessive iodine supplementation on thyroid function and morphology in non-iodine deficiency rat model].

OBJECTIVE: To study the effect of moderate and mild iodine excess on thyroid function and morphology in non iodine deficiency Wistar rats. METHODS: Serum thyroid-stimulating hormone (TSH) was measured with solid phase radioimmunoassay (IRMA) and serum total T(4) (TT(4)), TT(3), reverse T(3) (rT(3)) and thyroid TT(4) with radioimmunoassay (RIA). Cer-Arsenite colorimetric method was used to measure median urinary iodine (MUI). Thyroid morphological changes were observed under optical and electronic microscope. Metamorphic imaging system was used to measure the height of thyrocytes and the areas of thyroid follicular cavities. RESULTS: Iodine intake of three times than normal for 90 days could increase serum TSH but without significant difference; Serum TT(3) values were markedly lower than those in control, P = 0.0001. Serum and thyroid TT(4) values were markedly higher than those in double distilled water (DDW) group, P value being 0.001 and 0.0001 respectively. However, serum rT(3) did not change markedly when compared with that in DDW group. The area of follicular cavity increased, follicular cells became flat, nucleus stained darker, follicles broke and combined, giant follicles were formed, and the capillaries around the follicules were reduced. The height of thyrocytes was markedly lower than those in DDW group, while the areas of thyroid follicular cavities were markedly larger than those in DDW group (both P values were 0.001). Thyroid ultrastructure showed enlargement of endoplasmic reticulum of thyroid follicular cells, increase of number of secondary lysosomes, darker stain of nuclei, condensation of chromatin and reduction of microvilli. CONCLUSION: Iodine intake over 3 times than normal may potentiate the possibility of hypothyroidism and inhibit the function of most of thyrocytes in non iodine deficiency rats.