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Purpose Reduced physical activity is reported in the elderly, especially in institutional residents. Institutionalized older adults exhibit a high prevalence of frailty. In this work, we developed an artificial intelligence of things (AIoT)-based feedback assistive strengthening ergometer (AIFASE), for the physical strengthening of the elderly with intelligent assistance. Methods We conducted a 12-week intervention in a long-term care facility. In total, 16 participants (84.38 ± 6.0 years; 4 males and 12 females) were recruited with 1:1 randomization of exercise to control groups. The muscle strength of the lower extremities, timed up and go test (TUG), and Short-form Physical Performance Battery (SPPB) of the participants were measured. The AIFASE system allows the clinical staff to record the personal physical performance of the elderly and generates personalized exercise prescriptions accordingly. AIFASE also displays the current usage status of all ergometers and the users’ physiological conditions. The algorithms were developed to generate warning alerts when the training workload was too large by personal physiological detection. AIFASE automatically customized the exercise prescription according to the user’s exercise performance. Results After a 12-week AIFASE intervention, the intervention group exhibited significant improvements in the strength of the hip flexor, Semi-Tandem Stand, and Tandem Stand. Conclusion In this study, we developed an AIoT ergometer that delivered customized physical training prescriptions to improve the physical performance of long-term care facility residents. We believe that the application of AIFASE will help improve the quality of institutional care.

Comparison of the nanostructured Si photocathodes fabricated by chemical etching (c-Si), electrochemical etching (ec-Si) and photoelectrochemical etching (pec-Si) and their dramatically enhanced PEC water splitting.

Background/Purpose Concurrent sexually transmitted infections (STIs) are not uncommon in at-risk populations, for which control requires integrated testing, treatment and prevention. Methods From May, 2019 to February, 2020, multiplex real-time PCR assays were prospectively performed to detect Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Trichomonas vaginalis (TV) in the urine and rectal/vaginal swab specimens collected from HIV-positive patients with a history of STIs or symptoms suggestive of STIs. Patients confirmed to have acquired STIs were treated according to treatment guidelines. Results During the study period, 430 participants (99.1% men who have sex with men and median age 37 years) were included. The overall prevalence of CT, NG, and/or TV infection was 30.0%, including 24.7%, 12.1%, and 0.2% for CT, NG, and TV infection, respectively. The factors associated with CT, NG, and/or TV infection were hepatitis B surface antigen (HBsAg) seropositivity (AOR, 2.76; 95% CI, 1.22–6.26), recently acquired hepatitis C virus (HCV) infection (AOR, 5.62; 95% CI, 1.99–15.88), using mobile dating application (AOR, 2.08; 95% CI, 1.13–3.83), and oral sex (AOR, 2.12; 95% CI, 1.04–4.32). The rates of CT, NG, and/or TV infection were 50.0% in participants with recent HCV infection, 44.2% in those with HBsAg positivity, and 35.9% in those with incident syphilis. Among participants completing test-of-cure visits, the microbiological cure rate was 91.7% and 90.0% for chlamydia and gonorrhea, respectively. Conclusion HIV-positive participants had a high prevalence of CT and/or NG, especially those coinfected with viral hepatitis and syphilis. Our results strongly support integrated STI services in the population.

Rheumatoid arthritis (RA) and periodontitis are suggested to be closely linked based on microbial dysbiosis, but limited subgingival bacteria have been proven in the pathogenesis of RA. We enrolled 30 RA patients and 25 controls and divided them into three groups with matched age, gender, and diabetes statuses: group AM (all of the matched participants), group PD (periodontally diseased), and group PH (periodontally healthy). Their subgingival microbial composition was determined by V3–V4 16S rRNA gene sequencing. Significant differences in subgingival microbial clustering between the RA patients and controls were observed in groups AM and PD. Among the taxa enriched in RA, Aminipila butyrica and Peptococcus simiae were the only two species displaying positive correlation to the level of anti-citrullinated protein antibodies (ACPAs) in both of the groups. Surprisingly, the median of relative abundances of A. butyrica and P. simiae were 0% in the controls of group PD. Furthermore, a gene encoding arginine deiminase with the capability to produce citrulline was addressed in the complete genome sequence of A. butyrica. This is the first study to elucidate the important roles of A. butyrica and P. simiae as periodontal bacteria leading to RA possibly through the induction of ACPA production.

Since the water oxidation half-reaction requires the transfer of multi-electrons and the formation of O-O bond, it's crucial to investigate the catalytic behaviours of semiconductor photoanodes. In this work, a bio-inspired copper-bipyridine catalyst of Cu(dcbpy) is decorated on the nanoporous Si photoanode (black Si, b-Si). Under AM1.5G illumination, the b-Si/Cu(dcbpy) photoanode exhibits a high photocurrent density of 6.31 mA cm

To better understand the pharmacological characters of syringaldehyde (SA), which is a key-odorant compound of whisky and brandy, this review article is the first to compile the published literature for molecular docking that were subsequently validated by in vitro and in vivo assays to predict and develop insights into the medicinal properties of SA in terms of anti-oxidation, anti-inflammation, and anti-diabetes. The molecular docking displayed significantly binding affinity for SA towards tumor necrosis factor-α, interleukin-6, and antioxidant enzymes when inflammation from myocardial infarction and spinal cord ischemia. Moreover, SA nicely docked with dipeptidyl peptidase-IV, glucagon-like peptide 1 receptor, peroxisome proliferator-activated receptor, acetylcholine M2 receptor, and acetylcholinesterase in anti-diabetes investigations. These are associated with (1) an increase glucose utilization and insulin sensitivity to an anti-hyperglycemic effect; and (2) to potentiate intestinal contractility to abolish the α-amylase reaction when concurrently reducing retention time and glucose absorption of the intestinal tract to achieve a glucose-lowering effect. In silico screening of multi-targets concomitantly with preclinical tests could provide a potential exploration for new indications for drug discovery and development.

Yi-Jing Chen,1,2 Jing Chang,1 Si-Yu Yang3 1Department of Health Care Clinic, First Affiliated Hospital of Zhengzhou University, Henan, People’s Republic of China; 2Academy of Medical Science, Zhengzhou University, Henan, People’s Republic of China; 3Xiangya Medical School, Central South University, Changsha, People’s Republic of ChinaCorrespondence: Jing Chang Email jingchang101@163.comObjective: This study aimed to develop the ARMS-C and test its psychometric properties in hypertensive patients, to assess the level of medication adherence and to identify associated predictors for medication adherence and blood-pressure control among Chinese hypertensive patients.Methods: Hypertensive elderly who met inclusion criteria were recruited from an aged-care facility in Henan Province between January 2019 and July 2019. The patients completed the adapted ARMS-C. The scale’s factor structure, internal consistency, and construct validity were tested.Results: Good internal consistency (Cronbach’s α=0.89) and test–retest reliability (r=0.86, p< 0.01) were obtained. Item-total correlation coefficients for the ten-item ARMS-C were 0.505– 0.801. Factor analysis of construct validity identified two factors, explaining a total variance of 63.3%. Binary regression showed that patients with scores at level 2 (≤ 20 ARMS-10 scores < 30) were six times as likely to have blood pressure uncontrolled as those at level 1 (ARMS-10 scores < 20, OR 6.6, 95% CI 1.7– 25.1; p=0.006), and patients with scores at level 3 (ARMS-10 scores > 30) were 115 times as likely to have blood pressure uncontrolled as those at level 1 (ARMS-10 scores < 20,OR 115, 95% CI 9– 1,470; p=0).Conclusion: The ten-item ARMS-C is a reliable and valid self-reporting screening tool for adherence to medication and refills in elderly hypertensive Chinese patients.Keywords: adherence, 10-item ARMS, hypertension, blood-pressure control

Underclimate changes, extreme rainfall events can cause catastrophic sediment-related disasters such as large-scale landslides. To work on disaster prevention, the government has investigated the location of potential large-scale landslides by a geological and geomorphological approach. However, the activity of potential large-scale landslides has to rely on expensive on-site monitoring system, for example, observed drill hole of groundwater and underground displacement. Recently, the variation of stream electronic conductivity has been proposed to investigate the activity of large-scale landslide in Japan. Therefore, this study applied this concept in Taiwan. First, the temporal and spatial variations of stream electronic conductivity near the potential large-scale landslide have been surveyed. Accordingly, an interesting finding is that the spring water from the potential large-scale landslide can increase the concentration of chemical ion, and thus, the value of stream electronic conductivity increases. Second, the comparison of rainfall data, stream electronic conductivity, and ground surface displacement has been analyzed. There is a sound agreement between stream electronic conductivity and ground surface displacement. This result implied that stream electronic conductivity could be a possible index to monitoring the activity of potential large-scale landslides indirectly.

Circular dichroism (CD) has shown very interesting possibilities as a means to characterize the chiral signal of a chiral structure. Here, we theoretically demonstrated enhanced and tunable CD in the visible light regime using a composite structure consisting of a double-layer metal grating gaped by a dielectric waveguide layer. Based on the coupling of the waveguide modes and the localized plasmonic resonances, the CD could reach a maximum value as high as 0.52 at 635 nm, which is four times higher than the CD value obtained in a conventional double-layer grating without the waveguide coupling effect. Furthermore, the spectral positions of the enhanced CD bands could be easily tuned by controlling the structural parameters. The proposed hybrid double-grating and waveguide structures could have potential applications in chiral selective imaging, sensing and spectroscopy, especially where the transmission measurement is required.

Background The c.G6055A (p.G2019S) mutation in leucine-rich repeat kinase 2 (LRRK2) is the most prevalent genetic cause of Parkinson’s disease (PD). CRISPR/Cas9-mediated genome editing by homology-directed repair (HDR) has been applied to correct the mutation but may create small insertions and deletions (indels) due to double-strand DNA breaks. Adenine base editors (ABEs) could convert targeted A·T to G·C in genomic DNA without double-strand breaks. However, the correction efficiency of ABE in LRRK2 c.G6055A (p.G2019S) mutation remains unknown yet. This study aimed to compare the mutation correction efficiencies and off-target effects between HDR and ABEs in induced pluripotent stem cells (iPSCs) carrying LRRK2 c.G6055A (p.G2019S) mutation. Methods A set of mutation-corrected isogenic lines by editing the LRRK2 c.G6055A (p.G2019S) mutation in a PD patient-derived iPSC line using HDR or ABE were established. The mutation correction efficacies, off-target effects, and indels between HDR and ABE were compared. Comparative transcriptomic and proteomic analyses between the LRRK2 p.G2019S iPSCs and isogenic control cells were performed to identify novel molecular targets involved in LRRK2-parkinsonism pathways. Results ABE had a higher correction rate (13/53 clones, 24.5%) than HDR (3/47 clones, 6.4%). Twenty-seven HDR clones (57.4%), but no ABE clones, had deletions, though 14 ABE clones (26.4%) had off-target mutations. The corrected isogenic iPSC-derived dopaminergic neurons exhibited reduced LRRK2 kinase activity, decreased phospho-α-synuclein expression, and mitigated neurite shrinkage and apoptosis. Comparative transcriptomic and proteomic analysis identified different gene expression patterns in energy metabolism, protein degradation, and peroxisome proliferator-activated receptor pathways between the mutant and isogenic control cells. Conclusions The results of this study envision that ABE could directly correct the pathogenic mutation in iPSCs for reversing disease-related phenotypes in neuropathology and exploring novel pathophysiological targets in PD.

Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant neurodegenerative disorder caused by a CAG repeat expansion within the ATXN3/MJD1 gene. The expanded CAG repeats encode a polyglutamine (polyQ) tract at the C-terminus of the ATXN3 protein. ATXN3 containing expanded polyQ forms aggregates, leading to subsequent cellular dysfunctions including an impaired ubiquitin-proteasome system (UPS). To investigate the pathogenesis of SCA3 and develop potential therapeutic strategies, we established induced pluripotent stem cell (iPSC) lines from SCA3 patients (SCA3-iPSC). Neurons derived from SCA3-iPSCs formed aggregates that are positive to the polyQ marker 1C2. Treatment with the proteasome inhibitor, MG132, on SCA3-iPSC-derived neurons downregulated proteasome activity, increased production of radical oxygen species (ROS), and upregulated the cleaved caspase 3 level and caspase 3 activity. This increased susceptibility to the proteasome inhibitor can be rescued by a Chinese herbal medicine (CHM) extract NH037 (from Pueraria lobata) and its constituent daidzein via upregulating proteasome activity and reducing protein ubiquitination, oxidative stress, cleaved caspase 3 level, and caspase 3 activity. Our results successfully recapitulate the key phenotypes of the neurons derived from SCA3 patients, as well as indicate the potential of NH037 and daidzein in the treatment for SCA3 patients.

In capacitive deionization (CDI) systems, more Faradaic reactions generally occur at a higher cell voltage, resulting in the poor ion-removal efficiency and high energy consumption, but a low cell voltage may lead to a low deionization capacity. In this study, an integrated strategy, consisting of (1) selecting the acceptable charge/discharge time ratio, (2) finding the potential windows of both positive and negative electrodes, and (3) using the charge-balanced method for determining the optimal mass ratio between the positive and negative electrodes (denoted as (m+)/(m−)), is proposed to find the optimal cell voltage of a CDI system with a high desalination efficiency and low energy consumption. According to this strategy, two newly designed cells using two types of activated carbon (AC) show excellent CDI performances; cell 1 with AC = ACS679, (m+)/(m−) = 1:1.4, and cell voltage = 1.4 V: salt adsorption capacity of 12 mg g−1, charge efficiency of 62%, and energy consumption of 109 kJ mol−1 and cell 2 with AC = ACS25, (m+)/(m−) = 1:1, and cell voltage = 1.2 V: salt adsorption capacity of 13 mg g−1, charge efficiency of 81%, and energy consumption of 72 kJ mol−1 although the potential window of water decomposition for such AC-coated electrodes in 8 mM NaCl is about 2 V. This universal strategy is applicable to all CDI systems utilizing various electrode materials.

Viviparous (live-bearing) vertebrates have evolved repeatedly within otherwise oviparous (egg-laying) clades. Over two-thirds of these changes in vertebrate reproductive parity mode happened in squamate reptiles, where the transition has happened between 98 and 129 times. The transition from oviparity to viviparity requires numerous physiological, morphological, and immunological changes to the female reproductive tract, including eggshell reduction, delayed oviposition, placental development for supply of water and nutrition to the embryo by the mother, enhanced gas exchange, and suppression of maternal immune rejection of the embryo. We performed genomic and transcriptomic analyses of a closely related oviparous–viviparous pair of lizards ( Phrynocephalus przewalskii and Phrynocephalus vlangalii ) to examine these transitions. Expression patterns of maternal oviduct through reproductive development of the egg and embryo differ markedly between the two species. We found changes in expression patterns of appropriate genes that account for each of the major aspects of the oviparity to viviparity transition. In addition, we compared the gene sequences in transcriptomes of four oviparous–viviparous pairs of lizards in different genera ( Phrynocephalus , Eremias , Scincella , and Sphenomorphus ) to look for possible gene convergence at the sequence level. We discovered low levels of convergence in both amino acid replacement and evolutionary rate shift. This suggests that most of the changes that produce the oviparity–viviparity transition are changes in gene expression, so occasional reversals to oviparity from viviparity may not be as difficult to achieve as has been previously suggested.

The aim of this study was to retrospectively determine if quantitative measurements of computed tomography enterography (CTE) imaging findings correlate with histopathologic scores from biopsy specimens in patients with Crohn’s disease (CD). CTE datasets of 34 CD patients (19 male and 15 female) who underwent endoscopy with biopsy within 25 days before or after CTE were retrospectively reviewed. CTE findings of segmental mural hyperenhancement, wall thickening, mural stratification and mesenteric findings were quantitatively measured in the corresponding segment. Histopathologic score of CD was based upon the Naini Cortina scoring system. Correlation between CTE findings and histopathologic scores was assessed using Spearman’s rank correlation and logistic or linear regression analysis. Neutrophilic inflammation contributed the most to the segmental mural hyperenhancement and explained 38.4% of the variance (R2 = 0.384, P = 0.006). Moreover, the increased lymphocytes and plasma cells predicted larger lymph node (P = 0.003) and increased attenuation in mesenteric fat (P = 0.022). To a certain extent, macroscopic CTE findings may reflect the microscopic histopathologic state in the inflammatory stage of CD, underscoring that establishment of CTE scoring system may potentially provide an objective tool for assessment of disease progression.

Alzheimer’s disease (AD), probably caused by abnormal accumulation of β-amyloid (Aβ) and aberrant phosphorylation of tau, is the most common cause of dementia among older people. Generation of patient-specific neurons by induced pluripotent stem cell (iPSC) technology facilitates exploration of the disease features in live human neurons from AD patients. In this study, we generated iPSCs from two familial AD patients carrying a heterozygous D678H mutation in the APP gene (AD-iPSCs). The neurons derived from our AD-iPSCs demonstrated aberrant accumulation of intracellular and secreted Aβ42 and Aβ40, reduction of serine 9 phosphorylation in glycogen synthase kinase 3β (GSK3β) hyperphosphorylation of threonine 181 and serine 396 in tau protein, impaired neurite outgrowth, downregulation of synaptophysin, and increased caspase 1 activity. The comparison between neurons derived from a sibling pair of wild-type and mutated iPSCs successfully recapitulated these AD phenotypes. Treatment with indole compound NC009-1 (3-((1H-Indole-3-yl)methyl)-4-(2-nitrophenyl)but-3-en-2-one), a potential Aβ aggregation reducer, normalized the Aβ levels and GSK3β and tau phosphorylation, attenuated caspase 1 activity, and improved neurite outgrowth in AD-iPSC-derived neurons. Thus, APP D678H iPSCs-derived neurons recapitulate the cellular characteristics relevant to AD and enable exploration of the underlying pathogenesis and therapeutic strategies for AD.

Here we develop a novel but fundamental strategy for optimizing the ion-removal capacity of electrode materials in capacitive deionization (CDI) and inverted-capacitive deionization (i-CDI) systems without sacrificing their coulombic efficiency. The most efficient working cell voltages of different systems can be precisely determined by our newly designed cell voltage-programming method. We employ a palladium hydride reference electrode to monitor the electrode potentials of positive and negative electrodes during the double-layer charging-discharging processes. Accordingly, charge balance and maximum working cell voltages of CDI and i-CDI systems in brackish water can be achieved simultaneously to optimize the desalination efficiencies. Hence, the ion removal capability of an activated carbon//activated carbon (AC//AC) cell in 0.3–1.9 V reaches 12.2 mg g−1 with minor pH change in deionized solutions. The asymmetric CDI cell consisting of a positive graphene oxide-CNT composite and a negative AC electrode (GO@CNT//AC) is the most efficient CDI system with ion removal capacity of 21.3 mg g−1 in 0.2–1.45 V. The asymmetric AC//reduced GO-CNT composite (AC//rGO@CNT) cell is an exceptional i-CDI system which exhibits ion removal ability of 25.2 mg g−1 in 1.0–1.7 V. The above concepts in optimizing CDI/i-CDI performances are applicable to all types of electrode materials in various cell designs.

Excitotoxic damage caused by increased glutamate levels is involved in the pathogenesis of neurodegenerative diseases. Astaxanthin, a natural carotenoid with multiple health benefits, inhibits glutamate release from the brain tissue; however, whether it possesses the ability to affect glutamate-induced brain injury is unknown. The present study investigated the neuroprotective effects of astaxanthin on kainic acid (KA)-induced excitotoxicity in rats and the possible underlying intracellular signaling pathway. The rats were orally administrated with astaxanthin (50 or 100 mg/kg) for 7 days (once a day), and KA (15 mg/kg) was administered intraperitoneally at 1 h after the final administration. The results revealed that KA induced seizures, increased the hippocampal glutamate levels, caused considerable neuronal death and microglial activation in the hippocampal CA3 regions, and increased the production of proinflammatory cytokines. Astaxanthin pretreatment prevented these changes. Furthermore, astaxanthin pretreatment increased the expression of neuronal cell survival-related factors, including phosphorylated Akt, phosphorylated glycogen synthase kinase-3β, and Bcl-2 in the hippocampus of KA-injected rats. These results suggested that astaxanthin can attenuate seizures, mitigate inflammation, augment survival signals, and prevent hippocampal neuronal damage in the animal model of KA-induced excitotoxicity.

AimTissue microarray (TMA) is a powerful and effective tool for in situ tissue analysis. However, manual TMA construction methods showed varied qualities. This study aimed to raise a standardised TMA preparation technique that can be easily operated and is economical.MethodsA sampling needle was used to punch the tissue rods from the donor block and holes in the recipient block. To indicate the dots’ positions and ensure vertical punching, a novel auxiliary device made using commercial three-dimensional printing technology was attached. The TMA block was made up of tissue rods and a recipient block.ResultsA 77-rod (7×11) TMA block was constructed. The rows and columns were fixed in straight lines. There was no specimen loss during the process of embedding.ConclusionsAn alternative method for the construction of TMA blocks that met the basic requirement of many laboratories and can be effortlessly performed was presented.

Background The Qinghai-Tibetan Plateau (QTP) is the world’s highest and largest plateau, but the role of its uplift in the evolution of species or biotas still remains poorly known. Toad-headed lizards of the reproductively bimodal genus Phrynocephalus are a clade of agamids, with all viviparous species restricted to the QTP and adjacent regions. The eastern part of the range of the viviparous taxa is occupied by three closely related but taxonomically controversial species, P. guinanensis, P. putjatia and P. vlangalii. Here, we combined genetic (mitochondrial ND4 gene and nine microsatellite loci), morphological (11 mensural and 11 meristic variables), and ecological (nine climatic variables) data to explore possible scenarios that may explain the discordance between genetic and morphological patterns, and to test whether morphological divergence is associated with local adaptation. Results We found weak genetic differentiation but pronounced morphological divergence, especially between P. guinanensis and P. vlangalii. Genetically, the species boundary was not so clear between any species pair. Morphologically, the species boundary was clear between P. guinanensis and P. vlangalii but not between other two species pairs. Body size and scale characters accounted best for morphological divergence between species. Morphological divergence was related to habitat types that differ climatically. Conclusions Our study provides evidence for genetic and morphological divergence among the three closely related viviparous species of Phrynocephalus lizards, and supports the idea that natural selection in spatially heterogeneous environments can lead to population divergence even in the presence of gene flow. Our study supports the hypothesis that the evolutionary divergence between viviparous Phrynocephalus species was a consequence of environmental change after the uplift of the QTP. Electronic supplementary material The online version of this article (10.1186/s12862-019-1443-y) contains supplementary material, which is available to authorized users.

Parkinson’s disease (PD) is a common neurodegenerative disease accompanied by a loss of dopaminergic (DAergic) neurons. The development of therapies to prevent disease progression is the main goal of drug discovery. There is increasing evidence that oxidative stress and antioxidants may contribute to the pathogenesis and treatment of PD, respectively. In the present study, we investigated the antioxidative protective effects of the indole-derivative compound NC001-8 in DAergic neurons derived from SH-SY5Y cells and PD-specific induced pluripotent stem cells (PD-iPSCs) carrying a PARKIN ex5del mutation. In SH-SY5Y-differentiated DAergic neurons under 1-methyl-4-phenylpyridinium (MPP+) treatment, NC001-8 remarkably reduced the levels of reactive oxygen species (ROS) and cleaved caspase 3; upregulated nuclear factor erythroid 2-related factor 2 (NRF2) and NAD(P)H dehydrogenase, quinone 1 (NQO1); and promoted neuronal viability. In contrast, NRF2 knockdown abolished the effect of NC001-8 on the reduction of ROS and improvement of neuronal viability. In H2O2-treated DAergic neurons differentiated from PD-iPSCs, NC001-8 rescued the aberrant increase in ROS and cleaved caspase 3 by upregulating NRF2 and NQO1. Our results demonstrated the protective effect of NC001-8 in DAergic neurons via promoting the NRF2 antioxidative pathway and reducing ROS levels. We anticipate that our present in vitro assays may be a starting point for more sophisticated in vivo models or clinical trials that evaluate the potential of NC001-8 as a disease modifier for PD.

This paper explores the relationship among the job complexity of senior managers on their compensation and operating performances. The job complexity of senior managers is measured with proxy variables associated with operating activities. Simultaneous equations are then constructed to validate the endogenous relationships among these three factors. The empirical study indicates that the job complexity of senior managers is relevant to the improvement of operating performances and the level of executive compensation. This finding should serve as a reference for the information and electronics industry in the planning of executive compensation programs in order to enhance operating performances.

Summary Aims This study investigated the neuroprotective properties of icariin (an effective component of traditional Chinese herbal medicine Epimedium) on neuronal function and brain energy metabolism maintenance in a triple-transgenic mouse model of Alzheimer's disease (3 × Tg-AD). Methods 3 × Tg-AD mice as well as primary neurons were subjected to icariin treatment. Morris water maze assay, magnetic resonance spectroscopy (MRS), Western blotting, ELISA, and immunohistochemistry analysis were used to evaluate the effects of icariin administration. Results Icariin significantly improved spatial learning and memory retention in 3 × Tg-AD mice, promoted neuronal cell activity as identified by the enhancement of brain metabolite N-acetylaspartate level and ATP production in AD mice, preserved the expressions of mitochondrial key enzymes COX IV, PDHE1α, and synaptic protein PSD95, reduced Aβ plaque deposition in the cortex and hippocampus of AD mice, and inhibited β-site APP cleavage enzyme 1 (BACE1) expression. Icariin treatment also decreased the levels of extracellular and intracellular Aβ1-42 in 3 × Tg-AD primary neurons, modulated the distribution of Aβ along the neurites, and protected against mitochondrial fragmentation in 3 × Tg-AD neurons. Conclusions Icariin shows neuroprotective effects in 3 × Tg-AD mice and may be a promising multitarget drug in the prevention/protection against AD.

This paper investigates discriminating tongue features to distinguish between early stage breast cancer (BC) patients and non-breast cancer individuals through non-invasive traditional Chinese medicine (TCM) tongue diagnosis.The tongue features for 67 patients with 0 and 1 stages of BC, and 70 non-breast cancer individuals are extracted by the automatic tongue diagnosis system (ATDS). A total of nine tongue features, namely, tongue color, tongue quality, tongue fissure, tongue fur, red dot, ecchymosis, tooth mark, saliva, and tongue shape are identified for each tongue. Features extracted are further sub-divided according to the areas located, i.e., spleen-stomach, liver-gall-left, liver-gall-right, kidney, and heart-lung areas. This study focuses on deriving significant tongue features (p0.05) to discriminate early-stage BC patients from non-breast cancer individuals.The Mann-Whitney test shows that the amount of tongue fur (p=0.024), maximum covering area of tongue fur (p=0.009), thin tongue fur (p=0.009), the average area of red dot (p=0.049), the maximum area of red dot (p=0.009), red dot in the spleen-stomach area (p=0.000), and red dot in the heart-lung area (p=0.000) demonstrate significant differences. The data collected are further classified into two groups. The training group consists of 57 early-stage BC patients and 60 non-breast cancer individuals, while the testing group is composed of 10 early-stage BC patients and 10 non-breast cancer individuals. The logistic regression by utilizing these 7 tongue features with significant differences in Mann-Whitney test as factors is performed. In order to reduce the number of tongue features employed in prediction, tongue features with the least amount of significant difference, namely, maximum area of red dot and average area of red dot, are removed progressively. The tongue features of the testing group are employed in the aforementioned three models to test the power of significant tongue features identified in predicting early-stage BC. An accuracy of 80%, 80% and 90% is reached on non-breast cancer individuals by applying the 7, 6 and 5 significant tongue features obtained through Mann-Whitney test, respectively, while 60%, 60% and 50% is reached on the corresponding early-stage BC patients.The TCM tongue diagnosis can serve as a preliminary screening procedure in the early detection of BC in light of its simple and non-invasive nature, followed by other more accurate testing process. To the best of our knowledge, this is the first attempt in applying non-invasive TCM tongue diagnosis to the discrimination of early-stage BC patients and non-breast cancer individuals.

Triple-negative breast cancer (TNBC) is difficult to treat because there is no targeted therapy available. Clinical studies have demonstrated that S-phase kinase-associated protein 2 (Skp2) and low-density lipoprotein receptor-related protein 6 (LRP6) are highly expressed in TNBC. Therefore, therapeutic strategies designed to downregulate LRP6 or Skp2 may play an important clinical role in the treatment of TNBC. However, the regulatory effects of many drugs on Skp2 and LRP6 expression are currently unknown. In the present study, combined treatment with chrysin and 1,2,3,4,6-penta-O-galloyl-β-D-glucose (5GG) synergistically induced apoptosis and cell cycle arrest and inhibited cell proliferation and colony formation in AU565 and MDA-MB-231 human breast cancer cells. Furthermore, the combination of chrysin and 5GG suppressed tumor growth in nude mice with xenografted MDA-MB-231 cells by downregulating the phospho-LRP6 (pLRP6) and Skp2 proteins. Overall, our findings suggested that the combination of chrysin and 5GG has a potential therapeutic value in treating breast cancer, particularly for TNBC associated with Skp2/LRP6 overexpression, and hence warrants further investigation. © 2014 Wiley Periodicals, Inc.

Propofol is a widely used anesthetic. Many studies have shown that propofol has direct effects on blood vessels, but the precise mechanism is not fully understood. Secondary intrapulmonary artery rings from male rats were prepared and mounted in a Multi Myograph System. The following constrictors were used to induce contractions in isolated artery rings: high K(+) solution (60 mmol/L); U46619 solution (100 nmol/L); 5-hydroxytryptamine (5-HT; 3 µmol/L); or phenylephrine (Phe; 1 µmol/L). The relaxation effects of propofol were tested on high K(+) or U46619 precontracted rings. Propofol also was added to induce relaxation of rings preconstricted by U46619 after pretreatment with the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). The effects of propofol on Ca(2+) influx via the L-type Ca(2+) channels were evaluated by examining contraction-dependent responses to CaCl2 in the absence or presence of propofol (10 to 300 µmol/L). High K(+) solution and U46619 induced remarkable contractions of the rings, whereas contractions induced by 5-HT and Phe were weak. Propofol induced dose-dependent relaxation of artery rings precontracted by the high K(+) solution. Propofol also induced relaxation of rings precontracted by U46619 in an endothelium-independent way. Propofol at different concentrations significantly inhibited the Ca(2+)-induced contractions of pulmonary rings exposed to high K(+)-containing and Ca(2+)-free solution in a dose-dependent manner. Propofol relaxed vessels precontracted by the high K(+) solution and U46619 in an endothelium-independent way. The mechanism for this effect may involve inhibition of calcium influx through voltage-operated calcium channels (VOCCs) and receptor-operated calcium channels (ROCCs).

The role of cetuximab in treatment-related hematologic toxicity is not clear. We performed a meta-analysis of published randomized controlled trials (RCTs) to determine the overall risk of ≥grade 3 hematologic toxicity events (HTEs) associated with cetuximab. PubMed, EMBASE, and Web of Knowledge databases as well as abstracts presented at American Society of Clinical Oncology conferences and ClinicalTrials.gov were searched to identify relevant studies. Eligible studies included RCTs in which cetuximab in combination with chemotherapy or chemoradiotherapy was compared with chemotherapy or chemoradiotherapy alone. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using fixed- or random-effects models. A total of 11,234 patients with a variety of advanced solid tumors from 18 RCTs were included in the meta-analysis. Compared with chemotherapy alone, the addition of cetuximab was associated with increased risks of ≥grade 3 leucopenia/neutropenia and anemia events in colorectal cancer, with RRs of 1.16 (95% CI 1.05-1.27, p=0.002; incidence, 21.0 vs. 18.0%) and 2.67 (95% CI 1.53-4.65, p=0.01; incidence, 4.0 vs. 2.0%), respectively. Cetuximab was also associated with an increased risk of leucopenia/neutropenia in nonsmall cell lung cancer (NSCLC) (RR: 1.15; 95% CI 1.08-1.22, p

Early opportunity identification is critical for technology-based firms seeking to develop technology or product strategies for competitive advantage in the future. This research develops a patent mining approach based on the novelty detection statistical technique to identify unusual patents that may provide a fresh idea for potential opportunities. A natural language processing technique, latent semantic analysis, is applied to extract hidden relations between words in patent documents for alleviating the vocabulary mismatch problem and reducing the cumbersome efforts of keyword selection by experts. The angle-based outlier detection method, a novelty detection statistical technique, is used to determine outlier patents that are distinct from the majority of collected patent documents in a high-dimensional data space. Finally, visualization tools are developed to analyze the identified outlier patents for exploring potential technological opportunities. The developed methodology is applied in the telehealth industry and research findings can help telehealth firms formulate their technology strategies.