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Fibroblast growth-factor receptor (FGFR) is a potential target for cancer therapy. We designed three novel series of FGFR1 inhibitors bearing indazole, benzothiazole, and 1H-1,2,4-triazole scaffold via fragment-based virtual screening. All the newly synthesised compounds were evaluated in vitro for their inhibitory activities against FGFR1. Compound 9d bearing an indazole scaffold was first identified as a hit compound, with excellent kinase inhibitory activity (IC50 = 15.0 nM) and modest anti-proliferative activity (IC50 = 785.8 nM). Through two rounds of optimisation, the indazole derivative 9 u stood out as the most potent FGFR1 inhibitors with the best enzyme inhibitory activity (IC50 = 3.3 nM) and cellular activity (IC50 = 468.2 nM). Moreover, 9 u also exhibited good kinase selectivity. In addition, molecular docking study was performed to investigate the binding mode between target compounds and FGFR1. [ABSTRACT FROM AUTHOR]

Objectives: Whether a relationship between fish consumption and non-Hodgkin lymphoma (NHL) risk exists is an open issue. We carried out a meta-analysis to explore this association according to the published observational studies. Methods: We performed a search of databases in MEDLINE and EMBASE to identify relevant studies. We derived meta-analytic estimates using random-effects models, and assessed between-study heterogeneity using the Cochran's Q and I2 statistics. Results: We identified a total of seven case–control and two prospective cohort studies, including 7696 subjects with NHL. The summary relative risks (SRRs) estimated for NHL were 0.80 (95% confidence intervals (CIs): 0.68–0.94) for those in the highest fish consumption category compared with those in the lowest consumption category. There was evidence of significant heterogeneity across studies (Q = 26.72, Pheterogeneity = 0.002, I2 = 66.3%). Stratified analysis by study design indicated that a significant risk association between fish consumption and NHL was observed in case–control studies, but not in cohort studies. Based on the dose–response meta-analysis, the SRRs of NHL were 0.85 (95% CIs: 0.71–1.01) for three servings increased per week of fish consumed with evidence of significant heterogeneity (Pheterogeneity = 0.007, I2 = 63.9%). Conclusions: Findings from our meta-analysis indicate that consumption of fish may be not related to NHL risk. [ABSTRACT FROM AUTHOR]

Radiotherapy plays a major role in the curative treatment of head and neck cancer, either as a single modality therapy, or in combination with surgery or chemotherapy, or both. Despite advances to limit radiation-induced side-effects, the major salivary glands are often affected. This frequently leads to hyposalivation which causes an increased risk for xerostomia, dental caries, mucositis, and malnutrition culminating in a significant impact on patients' quality of life. Previous research demonstrated that loss of salivary function is associated with a decrease in polarity regulators and an increase in nuclear Yap localization in a putative stem and progenitor cell (SPC) population. Yap activation has been shown to be essential for regeneration in intestinal injury models; however, the highest levels of nuclear Yap are observed in irradiated salivary SPCs that do not regenerate the gland. Thus, elucidating the inputs that regulate nuclear Yap localization and determining the role that Yap plays within the entire tissue following radiation damage and during regeneration is critical. In this study, we demonstrate that radiation treatment increases nuclear Yap localization in acinar cells and Yap-regulated genes in parotid salivary tissues. Conversely, administration of insulin-like growth factor 1 (IGF1), known to restore salivary function in mouse models, reduces nuclear Yap localization and Yap transcriptional targets to levels similar to untreated tissues. Activation of Rho-associated protein kinase (ROCK) using calpeptin results in increased Yap-regulated genes in primary acinar cells while inhibition of ROCK activity (Y-27632) leads to decreased Yap transcriptional targets. These results suggest that Yap activity is dependent on ROCK activity and provides new mechanistic insights into the regulation of radiation-induced hyposalivation. [ABSTRACT FROM AUTHOR]

A new algorithm named the eight-section (ES) method for carrying out the interpolation for a magneto-resistive (MR) encoder is successfully developed and fabricated in a digital chip. It is known that a conventional magneto-resistive (MR) encoder employs the interpolation method, which converts incoming front-end analog signals in harmonics in sinusoids/co-sinusoids to moving displacement via calculating arc-tangents. This conventional interpolation requires divisions to be carried out for the displacement, which often leads to large noises while conducting digital computation, eventually undermining significantly the accuracy of the MR sensor. The proposed interpolation of eight-section (ES) is designed specially without divisions in the digital computation, leading to higher precision than the conventional interpolation conducting the computation of arc-tangents. The digital computation chip designed by this study consists of a cycle counter, two decimators for incoming analog signals of the MR sensor, a correcting circuit, and the proposal ES interpolation unit. The designed chip is successfully fabricated by TSMC 0.18-μm CMOS process, the area of which is 1643 × 1676 μm. The chip is than calibrated by a reference interferometer by experiments for further improving the measurement accuracy. The precision finally results in measuring displacement reaches as accurate as within 1.065 μm, which is much favorable to the existing performance around 2 μm by the conventional interpolation. [ABSTRACT FROM AUTHOR]

Aims: To determine deficiencies in the Food and Drug Administration (FDA)'s guidance for assessing acarbose bioequivalence (BE) and to explore optimal pharmacodynamic (PD) metrics for better evaluation of acarbose BE. Methods: Three clinical trials with branded acarbose were conducted in healthy subjects, including a pilot study (Study I, n = 11, 50 and 100 mg), a 2×2 crossover BE study (Study II, n = 36, 100 mg) and a 4×4 Williams study (Study III, n = 16, 50/100/150 mg). Serum glucose concentrations were measured by the glucose oxidase method. Results: In Study I, compared with 50 mg acarbose, only 100 mg acarbose had a significantly lower Cmax0–4h than that of sucrose administration alone (7.96 ± 0.83 mmol/L vs 6.78 ± 1.02 mmol/L, P <.05). In Study II, the geometric mean ratios of the test formulation to the reference formulation (both formulations were the branded drug) for FDA PD metrics, ΔCmax0–4h and ΔAUC0–4h, were 0.903 and 0.776, respectively, and the 90% confidence intervals were 67.44–120.90 and 53.65–112.13, respectively. The geometric mean ratios (confidence interval) for possible optimal evaluation PD metrics (Cmax0–2h and AUC0–2h) were 1.035 (94.23–112.68) and 0.982 (89.28–107.17), respectively. Further, Cmax0–2h and AUC0–2h also met the sensitivity requirements for BE evaluation in Study III. Conclusion: Considering the mechanisms of action of acarbose, the PD effect was shown to be dose independent during the 2–4 hours postadministration of acarbose. Hence PD metrics based on the serum glucose concentration from 0 to 2 hours (Cmax0–2h and AUC0–2h) are more sensitive than the FDA‐recommended PD metrics for acarbose BE evaluation from 0–4 hours (ΔCmax0–4h and ΔAUC0–4h). The trial has been registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn, ChiCTR1800015795, ChiCTR‐IIR‐17013918, ChiCTR‐IIR‐17011903). All subjects provided written informed consent before screening. [ABSTRACT FROM AUTHOR]

Bacteria‐mediated tumor therapy (BMTT) has been known for decades; however, its clinical use is inhibited by its association with infections. To address this issue, a spiky, bacterium‐like metal–organic framework (MOF), which can replicate the functional responses of BMTT without its adverse side‐effects, is proposed. MOFs are synthesized in a solvothermal reaction of aluminum sulfate, ruthenium chloride hydrate, and 2‐aminoterephthalic acid; they have a spherical morphology or many nanospikes on their surfaces, depending on the reaction temperature. Both spherical and spiky MOFs can function as photothermal agents, converting absorbed optical energy into local heat. Owing to their higher surface area of interaction, spiky MOFs are more easily phagocytosed by macrophages than are spherical MOFs, strengthening their immune responses. Moreover, when injected intratumorally, spiky MOFs reside significantly longer than spherical ones, enabling their use in repeated photothermal treatments. The combination of in situ vaccination with intratumorally injected bacterium‐like MOFs under exposure to an near‐infrared laser and the immune checkpoint blockade of systemically administered αPD‐1 is evaluated in tumor‐bearing mice. The results indicate that the checkpoint blockade acts synergistically with in situ vaccination to provide diverse antitumor functions of BMTT, destroying a primary tumor and suppressing tumor recurrence and metastasis. [ABSTRACT FROM AUTHOR]

Complexity and abundant dynamics may arise in locally-active systems only, in which locally-active elements are essential to amplify infinitesimal fluctuation signals and maintain oscillating. It has been recently found that some memristors may act as locally-active elements under suitable biasing. A number of important engineering applications would benefit from locally-active memristors. The aim of this paper is to show that locally-active memristor-based circuits can generate periodic and chaotic oscillations. To this end, we propose a non-volatile locally-active memristor, which has two asymptotically stable equilibrium points (or two non-volatile memristances) and globally-passive but locally-active characteristic. At an operating point in the locally-active region, a small-signal equivalent circuit is derived for describing the characteristics of the memristor near the operating point. By using the small-signal equivalent circuit, we show that the memristor possesses an edge of chaos in a voltage range, and that the memristor, when connected in series with an inductor, can oscillate about a locally-active operating point in the edge of chaos. And the oscillating frequency and the external inductance are determined by the small-signal admittance Y(iω). Furthermore, if the parasitic capacitor in parallel with the memristor is considered in the periodic oscillating circuit, the circuit generates chaotic oscillations. [ABSTRACT FROM AUTHOR]

In2O3@Cu2MoS4 nanocomposite with superior photoelectrochemical (PEC) performance is used for the first time as a photoactivity material, and a signal-off PEC biosensing platform for miRNA detection has been successfully constructed. Firstly, the Cu2MoS4 nanosheets are synthesized by a hydrothermal method, and then, the homogeneous In2O3 nanoparticles (In2O3 NPs) are synthesized by calcination in the air. The In2O3@Cu2MoS4 nanocomposite is constructed with the Cu2MoS4 nanosheets as matrix and In2O3 NPs as sensitizer through a layer-by-layer assembly strategy. The nanocomposite with a tight interface and the matched band structure restrains the electron-hole pair recombination. Under visible light (400–700 nm), the nanocomposite exhibits a strong initial signal. With the catalyzed hairpin assembly, dozens of PbS quantum dots (QDs) are introduced on the surface of an electrode, significantly reducing the photocurrent of n-type In2O3@Cu2MoS4. Since PbS QDs can compete with the nanocomposite for light energy and electron donors, the signal decreased. Under optimal conditions, the biosensor manifests a broad linear range (1 fM–1 nM) and a low detection limit of about 0.57 fM, at a working potential of 0 V (vs. Ag/AgCl). The recovery of spiked human serum is between 94.0 and 102%, and the relative standard deviation (RSD) is between 1.3 and 2.7%. Therefore, the as-fabricated biosensor exhibits a potential for the determination of miRNA-21 in practical applications. Graphical abstract [ABSTRACT FROM AUTHOR]

To facilitate the cell-based experiment for pulsed electromagnetic field biological effect study, a novel TEM-cell-integrated CO2 incubator was developed. The integrated experimental system could simultaneously meet the requirement of standard cell culture condition and the various Transient Electromagnetic Field (TEF) exposure, which made it possible to study the relationship between different electromagnetic pulse exposure and the cellular responses in a reliable way. During the research, a comparison experiment was carried out to evaluate the necessity of the integrated incubator system: firstly, two different types of cell lines, which are the human prostate cancer cell line (PC3) and the pancreatic β cell line (MIN6) were chosen and exposed in the TEM-cell which located in the open area and the integrated system, respectively, with the same EFT radiation conditions; then, the cells' viability, the cellular ROS level and the mitochondrial membrane potential (MMP) were detected, respectively. The results showed that in the same parameter of the EFT radiation, the processes of the cells had a significant difference and even opposite in the incubator and open area, and all the results could be reproducible. The phenomenon indicated the stability of the TEM-cell-integrated CO2 incubator, and also demonstrated the necessity to strictly control the cell culture condition when carrying out the precise mechanism study of the TEF bioresponse at the cellular levels. [ABSTRACT FROM AUTHOR]

A selective recovery process for cobalt from the cathode materials of Li-ion batteries is demonstrated in this report. First, acid leaching was applied to dissolve the metals from the lithium-metal oxides. It was found out that with the assistance of probe type ultrasonication, manganese could be simultaneously separated by precipitation. This phenomenon would reduce the difficulty for later separation. Next, water-in-oil microemulsion extraction was applied for direct extraction of cobalt from the other metals. The cobalt extraction yield was 98% and purity was 96%. Moreover, the microemulsion system could be reused for 100 times without losing its extraction ability. [ABSTRACT FROM AUTHOR]

Cerebellum has been implicated in drug addiction; however, its underlying cellular populations and neuronal circuitry remain largely unknown. In the current study, we identified a neural pathway from tyrosine hydroxylase (TH)-positive Purkinje cells (PCTH+) in cerebellar lobule VI to calcium/calmodulin-dependent protein kinase II (CaMKII)-positive glutamatergic neurons in the medial cerebellar nucleus (MedCaMKII), forming the lobule VI PCTH+-MedCaMKII pathway in male mice. In naive male mice, inhibition of PCTH+ neurons activated Med neurons. During conditioned place preference (CPP) training, exposure to methamphetamine (METH) inhibited lobule VI PCTH+ neurons while excited MedCaMKII neurons in mice. Silencing MedCaMKII using a tetanus toxin light chain (tettox) suppressed the acquisition of METH CPP in mice but resulted in motor coordination deficits in naive mice. In contrast, activating lobule VI PCTH+ terminals within Med inhibited the activity of Med neurons and subsequently blocked the acquisition of METH CPP in mice without affecting motor coordination, locomotor activity, and sucrose reinforcements in naive mice. Our findings identified a novel lobule VI PCTH+-MedCaMKII pathway within the cerebellum and explored its role in mediating the acquisition of METH-preferred behaviors. [ABSTRACT FROM AUTHOR]

Chiggers are a group of ectoparasites and they are the vector of scrub typhus. Although the Ryukyu mouse (Mus caroli) is a common species of rodent in some outdoor habitats, few studies are about the mouse itself and its ectoparasites. To date, there has been no specific report on chiggers of M. caroli. Based on the field investigation in southwest China from 2001 to 2019, this paper reported the infestation and distribution of chiggers on M. caroli for the first time. Among the 91 sites investigated, 263 Ryukyu mice were captured at 18 sites, and 678 chiggers were collected from the mice. The collected chiggers were identified to be one family, two subfamilies, six genera, and 16 species with relatively low species diversity. The overall infestation prevalence (PM), mean abundance (MA), and mean intensity (MI) were PM = 27.38%, MA = 2.58 chiggers/per mouse, and MI = 9.42 chiggers/per mouse respectively. The dominant chigger species are Walchia ewingi and W. micropelta with a total constituent ratio of Cr = 94.10% (638/678), and they were of aggregated distribution among different individuals of the host M. caroli. The distribution of two dominant chigger species seemed to be mutually independent with the association coefficient V ≈ 0 (p < 0.001). The infestation (PM, MA, and MI) of M. caroli with chiggers greatly fluctuated in different geographical landscapes, altitudes, and latitudes with an obvious environmental heterogeneity. The male and adult M. caroli harbored much more chigger mites with significantly higher infestations (PM, MA and MI) than the female and juvenile mice. The theoretical curve of species abundance distribution of the chigger mite community on M. caroli was fitted by Preston lognormal distribution model with fitting goodness R2 = 0.77. Based on the iChao1 formula, the expected total number of chigger species on the mice was estimated to be 24 species. [ABSTRACT FROM AUTHOR]

The systematic review was used to evaluate the relationship between fundamental movement skills (FMS) and physical activity (PA) in preschoolers. PubMed, Science Direct, Web of Science, CNKI, and Wanfang databases were searched for terms related to preschoolers' FMS and PA from the establishment to July, 2022. 21 cross-sectional studies and 5 longitudinal studies with 6561 preschoolers were included. There was a significant positive association between FMS and moderate-to-vigorous physical activity (MVPA) (r = 0.25, 95%CI 0.22∼0.27) and total physical activity(TPA) (r = 0.23, 95%CI 0.19∼0.27). The locomotor and object control skills were significant positive association with both MVPA and TPA. There is a significant positive association between FMS and MVPA as well as between FMS and TPA, indicating the movement proficiency is associated with increased PA and vice versa. [ABSTRACT FROM AUTHOR]

An economical and stable single-shot pulse picker design without dispersion, nonlinear effect, and limitation on wavelength is proposed. This design is composed of a periodic pulse blocker (PPB), a control unit, and a mechanical shutter. It has successfully been applied to the commercial high-fluence femtosecond laser with 11-mm beam diameter, 2-mJ pulse energy, and 1-kHz repetition rate. Significantly, by incorporating commercial optical choppers equipped with custom-designed chopper blades in the PPB, this design can accommodate lasers with fluences reaching 610 mJ/cm2 and the standard 1 kHz repetition rate typical of high-fluence lasers. Furthermore, the proposed design provides a cost-effective substitute compared to using electro-optic modulators or acousto-optic modulators. [ABSTRACT FROM AUTHOR]

Surface-specific sum frequency generation vibrational spectroscopy is applied to study the molecular configuration of short-chain n-alkanethiol self-assembled monolayers (SAMs with n = 2–6) on the Au surface. For monolayers with n ≥ 3, the alkanethiols are upright-oriented, with the CH3 tilt angle varying between ∼33° and ∼46° in clear even–odd dependency. The ethanethiol monolayer (n = 2) is, however, found to exhibit a distinct lying-down configuration with a larger methyl tilt angle (67°–79°) and a smaller CH2 tilt angle (56°–68°). Such a unique configurational transition from n = 2 to n ≥ 3 discloses the steric effect owing to chain–chain interaction among neighboring molecules. Through density functional theory calculations, the transition is further confirmed to be energetically favorable for thiols on a defective reconstructed Au(111) surface but not on the pristine one. Our study highlights the roles of the chain–chain interaction and the substrate surface atomic structure when organizing SAMs, offering a strategic pathway for exploiting their applications. [ABSTRACT FROM AUTHOR]

Arabidopsis AINTEGUMENTA (ANT), an AP2 transcription factor, is known to control plant growth and floral organogenesis. In this study, our transcriptome analysis and in situ hybridization assays of maize embryonic leaves suggested that maize ANT1 (ZmANT1) regulates vascular development. To better understand ANT1 functions, we determined the binding motif of ZmANT1 and then showed that ZmANT1 binds the promoters of millet SCR1, GNC, and AN3, which are key regulators of Kranz anatomy, chloroplast development, and plant growth, respectively. We generated a mutant with a single-codon deletion and two frameshift mutants of the ANT1 ortholog in the C4millet Setaria viridis by the CRISPR/Cas9 technique. The two frameshift mutants displayed reduced photosynthesis efficiency and growth rate, smaller leaves, and lower grain yields than wild-type (WT) plants. Moreover, their leaves sporadically exhibited distorted Kranz anatomy and vein spacing. Conducting transcriptomic analysis of developing leaves in the WT and the three mutants we identified differentially expressed genes (DEGs) in the two frameshift mutant lines and found many downregulated DEGs enriched in photosynthesis, heme, tetrapyrrole binding, and antioxidant activity. In addition, we predicted many target genes of ZmANT1 and chose 13 of them to confirm binding of ZmANT1 to their promoters. Based on the above observations, we proposed a model for ANT1 regulation of cell proliferation and leaf growth, vascular and vein development, chloroplast development, and photosynthesis through its target genes. Our study revealed biological roles of ANT1 in several developmental processes beyond its known roles in plant growth and floral organogenesis. [ABSTRACT FROM AUTHOR]

A disintegrin and metalloprotease with thrombospondin motifs (ADAMTS) family are widely implicated in tissue remodeling events manifested in cancer development. ADAMTS1, the most fully characterized ADAMTS, plays conflicting roles in different cancer types; however, the role of ADAMTS1 in renal cell carcinoma (RCC) remains unclear. Herein, we found that ADAMTS1 is highly expressed in RCC tissues compared to normal renal tissues, and its expression was correlated with an advanced stage and a poor prognosis of RCC patients. In vitro, we observed higher expression of ADAMTS1 in metastatic (m)RCC cells compared to primary cells, and manipulation of ADAMTS1 expression affected cell invasion and clonogenicity. Results from protease array showed that ADAMTS1 is modulated by melatonin through mechanisms independent of the MT1 receptor in mRCC cells, and overexpression of ADAMTS1 relieved the invasion/clonogenicity and growth/metastasis inhibition imposed by melatonin treatment in vitro and in an orthotopic xenograft model. The human microRNA (miR) OneArray showed that miR‐181d and miR‐let‐7f were induced by melatonin and, respectively, targeted the 3'‐UTR and non‐3'‐UTR of ADAMTS1 to suppress its expression and mRCC invasive ability. Clinically, RCC patients with high levels of miR‐181d or miR‐let‐7f and a low level of ADAMTS1 had the most favorable prognoses. In addition, ubiquitin/proteasome‐mediated degradation of ADAMTS1 can also be triggered by melatonin. Together, our study indicates that ADAMTS1 may be a useful biomarker for predicting RCC progression. The novel convergence between melatonin and ADAMTS1 post‐transcriptional and post‐translational regulation provides new insights into the role of melatonin‐induced molecular regulation in suppressing RCC progression. [ABSTRACT FROM AUTHOR]

The inhibition of soluble epoxide hydrolase (sEH) is regarded as a promising therapeutic approach to treat inflammation and its related disorders. In present work, we investigated inhibitory effects of forty-nine kinds of traditional Chinese medicines against sEH. Inula helenium showed significant inhibitory effect against sEH, and the extract of I. helenium was isolated to obtain eight compounds, including 4 H -tomentosin (1), xanthalongin (2), linoleic acid (3), 8-hydroxy-9-isobutyryloxy-10(2)-methylbutyrylthymol (4), dehydrocostus lactone (5), alantolactone (6), costunolide (7), and isoalantolactone (8). Among them, 4 H -tomentosin (1), xanthalongin (2), and linoleic acid (3) showed significantly inhibitory activities on sEH with half maximal inhibitory concentration (IC 50) from 5.88 ± 0.97 μM to 11.63 ± 0.58 μM. The inhibition kinetics suggested that 4 H -tomentosin (1) and xanthalongin (2) were mixed-competitive type inhibitors with inhibition constants (K i) of 7.02 and 6.57 μM, respectively, and linoleic acid (3) was a competitive type inhibitor with a K i values of 3.52 μM. The potential interactions of 4 H -tomentosin (1), xanthalongin (2), and linoleic acid (3) with sEH were analyzed by molecular docking, which indicated that these bioactive compounds had interactions with key amino acid residues Tyr343, Ile363, Tyr383, and His524. • Eight compounds were isolated from I. helenium. • Compounds 1-3 could inhibit sEH activity with IC 50 values from 5.88 ± 0.97 μM to 11.63 ± 0.58 μM. • They were all mixed-competitive type inhibitor with Ki values from 3.52 μM to 7.02 μM • Molecular docking revealed interaction of compounds 1-3 with sEH. [ABSTRACT FROM AUTHOR]

Background: The coronavirus disease 2019 (COVID-19) epidemic met coincidentally with massive migration before Lunar New Year in China in early 2020. This study is to investigate the relationship between the massive migration and the coronavirus disease 2019 (COVID-19) epidemic in China. Methods: The epidemic data between January 25th and February 15th and migration data between Jan 1st and Jan 24th were collected from the official websites. Using the R package WGCNA, we established a scale-free network of the selected cities. Correlation analysis was applied to describe the correlation between the Spring Migration and COVID-19 epidemic. Results: The epidemic seriousness in Hubei (except the city of Wuhan) was closely correlated with the migration from Wuhan between January 10 and January 24, 2020. The epidemic seriousness in the other provinces, municipalities and autonomous regions was largely affected by the immigration from Wuhan. By establishing a scale-free network of the regions, we divided the regions into two modules. The regions in the brown module consisted of three municipalities, nine provincial capitals and other 12 cities. The COVID-19 epidemics in these regions were more likely to be aggravated by migration. Conclusions: The migration from Wuhan could partly explain the epidemic seriousness in Hubei Province and other regions. The scale-free network we have established can better evaluate the epidemic. Three municipalities (Beijing, Shanghai and Tianjin), eight provincial capitals (including Nanjing, Changsha et al.) and 12 other cities (including Qingdao, Zhongshan, Shenzhen et al.) were hub cities in the spread of COVID-19 in China. [ABSTRACT FROM AUTHOR]

microRNA‐3607 (miR‐3607) has been identified as an important biomarker, and its aberrant expression exerts a significant role in tumorigenesis. However, the biological function of miR‐3607 in hepatocellular carcinoma (HCC) needs to be deciphered comprehensively. Clinical samples of HCC patients, as well as normal cases, were derived from The Cancer Genome Atlas database. Quantitative reverse transcription polymerase chain reaction (qRT‐PCR) and Western blotting analyses were utilized to detect the expression levels of indicated genes. Cell counting kit‐8 (CCK‐8), colony formation, and transwell assays were performed to assess the effect of miR‐3607 in HCC cell viability, migration, and invasion. Bioinformatics analysis and luciferase reporter gene assay was applied to screen the target genes of miR‐3607 and verified the association between miR‐3607 and its potential target gene. Our study showed that miR‐3607 expression was decreased in HCC tissues and cell lines, and its downregulation was linked with poor outcomes of HCC patients. miR‐3607 was noted to inhibit HCC cell growth, colony formation, migration, and invasion. Besides, minichromosome maintenance (MCM5) was a possible target gene of miR‐3607 in HCC. Overexpression of MCM5 was observed in HCC and induced unfavorable prognosis. MCM5 expression had a negative correlation with miR‐3607. MCM5 can abolish the suppressive impacts of miR‐3607 on HCC cell malignant behaviors and the epithelial‐mesenchymal transition (EMT) process. To sum up, our results unveiled that miR‐3607 could inhibit HCC cell growth, migration, and invasion by regulating MCM5 and mediating EMT process, suggesting a new probable biomarker for further treatment of HCC. [ABSTRACT FROM AUTHOR]

Brain function has been implicated to control the aging process and modulate lifespan. However, continuous efforts remain for the identification of the minimal sufficient brain region and the underlying mechanism for neuronal regulation of longevity. Here, we show that the Drosophila lifespan is modulated by rab27 functioning in a small subset of neurons of the mushroom bodies (MB), a brain structure that shares analogous functions with mammalian hippocampus and hypothalamus. Depleting rab27 in the α/βp neurons of the MB is sufficient to extend lifespan, enhance systemic stress responses, and alter energy homeostasis, all without trade‐offs in major life functions. Within the α/βp neurons, rab27KO causes the mislocalization of phosphorylated S6K thus attenuates TOR signaling, resulting in decreased protein synthesis and reduced neuronal activity. Consistently, expression of dominant‐negative S6K in the α/βp neurons increases lifespan. Furthermore, the expression of phospho‐mimetic S6 in α/βp neurons of rab27KO rescued local protein synthesis and reversed lifespan extension. These findings demonstrate that inhibiting TOR‐mediated protein synthesis in α/βp neurons is sufficient to promote longevity. [ABSTRACT FROM AUTHOR]

Background: It has previously been shown that bevacizumab, when added to chemotherapy, improved overall survival in several cancers. In glioblastoma multiforme (GBM), bevacizumab increased progression-free survival and it is widely used for tumor recurrence, though it has failed to improve overall survival (OS) in controlled trials. However, an effective biomarker for predicting the prognosis of bevacizumab treatment has yet to be identified. This study, therefore, aimed to retrospectively analyze the polymorphisms of p53 codon 72 and the clinical characteristics of GBM specimens from Taiwanese patients.Methods: The polymorphisms of p53 codon 72 in 99 patients with GBM treated at Taichung Veterans General Hospital in Taiwan from 2007 to 2017 were analyzed using direct DNA sequencing and PCR-RFLP analysis.Results: We found that among these GBM patients, the distribution of codon 72 polymorphisms was 28.3% for proline homozygotes (Pro/Pro), 38.4% for arginine homozygotes (Arg/Arg), and 33.3% for proline/arginine heterozygotes (Pro/Arg). Although the polymorphisms of p53 codon 72 were not directly associated with the overall survival of GBM, both the Arg/Arg and Arg/Pro genotypes were associated with significant benefits in terms of overall survival in patients treated with CCRT plus bevacizumab compared to patients treated with CCRT alone.Conclusions: This pilot study suggests that both the Arg/Arg and Arg/Pro genotypes of p53 codon 72 polymorphism may have value as independent prognostic or predictive parameters for bevacizumab treatment response and failure. Relatedly, the results of the study further demonstrate the utility of stratifying GBM patients according to bevacizumab sensitivity. [ABSTRACT FROM AUTHOR]

Aims: To explore the concerns and experiences of parents of children scheduled to receive allogeneic haematopoietic stem cell transplantation. Design: A qualitative secondary analysis of interview data from an intervention study. Methods: A total of 28 parents (4 fathers and 24 mothers) were recruited from a children's hospital, which performs approximately one‐third of all paediatric haematopoietic stem cell transplantation cases in Taiwan. Data were collected between September 2015–August 2018 by one researcher with face‐to‐face interviews, which were tape‐recorded and transcribed verbatim. The data were analysed using inductive content analysis to extract the main themes. Results: Five themes describing parental concerns prior to paediatric haematopoietic stem cell transplantation were identified: the child became their first priority, seeking solutions, an interweaving of hope and uncertainty, grateful for the chance of a cure and the long road to recovery. Conclusion: Understanding the concerns and experiences of our participants as they navigated the pre‐transplantation period could reduce parents' uncertainty and improve the care of their child. Impact: These experiences provide information that could be used by healthcare professionals to develop support interventions and strategies tailored to the individual needs of each parent, which could prepare parents for their child's haematopoietic stem cell transplantation. [ABSTRACT FROM AUTHOR]

Objectives: Peripheral arterial disease (PAD) is characterised by arterial occlusion and fibrosis in the lower extremities. Extracellular volume matrix fraction (ECV) is a biomarker of skeletal muscle fibrosis, but has not been applied to the lower extremities with PAD. This study investigated the clinical feasibility of using ECV for calf muscle fibrosis quantification by comparing normal controls (NC) and PAD patients.Methods: From October 2016 to December 2017, we recruited patients with PAD, and patients with head and neck cancer receiving fibular flap as NC group. All participants underwent magnetic resonance imaging (MRI) to determine the ECV of the calves and the differences between the NC and PAD groups. ECV was calculated from T1 values at steady-state equilibrium, defined as the point in time after contrast agent injection when the variance of T1 relaxation time in blood and muscle becomes less than 5%.Results: A total of 46 patients (18 in the NC group and 28 in the PAD group) were recruited. Steady-state equilibrium was reached at 11-12 min after contrast agent injection. The NC group had significantly lower mean ECV than the PAD group (12.71% vs. 31.92%, respectively, p < 0.001). In the PAD group, the mean ECV was slightly lower in patients with collateral vessels than in those without (26.58% vs. 34.88%, respectively, p = 0.047).Conclusion: Evaluation of skeletal fibrosis in PAD using ECV is feasible. ECV can help identify PAD patients with collateral vessel formation and lay the foundation for future research in PAD management.Key Points: • Steady-state equilibrium for ECV measurement of the lower limbs can be reached at around 11-12 min. • Quantification of lower limb muscle fibrosis by measuring ECV is clinically feasible and can be used to differentiate between patients with PAD and histologically proven normal controls. • ECV can differentiate PAD patients with or without visible collateral vessels, further expanding its role in identifying the presence of collateral supply in clinical decision-making. [ABSTRACT FROM AUTHOR]

C24H26Cu2N8O27, triclinic, P1 (no. 2), a = 4.7705(1) Å, b = 14.6219(5) Å, c = 14.7418(3) Å, α = 61.225(3)°, β = 85.342(2)°, γ = 83.938(2)°, V = 895.73(5) Å3, Z = 1, Rgt(F) = 0.0485, wRref(F2) = 0.1341, T = 170.0 K. [ABSTRACT FROM AUTHOR]

In this paper, a half-space fast multipole BEM is developed for the simulation of three-dimensional acoustic problems above an infinite impedance plane. The half-space impedance Green's function involving a complex line source is used, so that both mass-like and spring-like impedance boundary conditions on the infinite plane can be explicitly satisfied and the infinite plane is not required to be discretized. The Burton–Miller method is employed to tackle the fictitious eigenfrequency problem involved in the conventional boundary integral equation method. Image relations of the multipole expansion coefficients are used and the half-space impedance Green's function is modified to apply such relations to avoid calculating, translating and saving the multipole/local expansion coefficients in the image domain. An automatic integrator with adaptive interval subdivision is further adopted to calculate the line integral contained in the M2L translation formula accurately and efficiently. Numerical examples are given to show the validity and potential of the method. [ABSTRACT FROM AUTHOR]

We demonstrate the transmission of a microwave frequency signal at 10 GHz over a 112-km urban fiber link based on a novel simple-architecture electronic phase compensation system. The key element of the system is the low noise frequency divider by 4 to differentiate the frequency of the forward signal from that of the backward one, thus suppressing the effect of Brillouin backscattering and parasitic reflection along the link. In terms of overlapping Allan deviation, the frequency transfer instability of 4.2 × 10−15 at 1-s integration time and 1.6 × 10−18 at one-day integration time was achieved. In addition, its sensitivity to the polarization mode dispersion in fiber is analyzed by comparing the results with and without laser polarization scrambling. Generally, with simplicity and robustness, the system can offer great potentials in constructing cascaded frequency transfer system and facilitate the building of fiber-based microwave transfer network. [ABSTRACT FROM AUTHOR]

aimed to investigate the tumor-suppressive role of miR-199a-3p targeted ZEB1. Materials and Methods: A549 cells were transfected with ZEB1 and/or miR-199a-3p. Then, tumor growth was investigated in xenograft mice. Stem-like property, proliferation and mitochondria injury were further validated in vitro. Results: Overexpression of miR-199a-3p with premiRNAs significantly reduced tumor growth inhibited CD44 and Ki67 and increased Caspase-3 in A549 xenograft mice. Sphere formation and protein expression of stem-like markers showed that miR-199a-3p inhibited stemness of A549 cell. miR-199a-3p reduced proliferation of A549 cells, as showed with EdU staining and reduced expression of Ki67. Transfection of miR-199a-3p also promoted apoptosis, as indicated with increased apoptotic cells with flow cytometry, and increased cleaved Caspase-3/Caspase3 and Bcl-2/Bax. Apoptosis was further validated to be induced with mitochondria dysfunction, which indicated with JC-1 labeled loss of mitochondrial membrane potential, reduced activity of SOD, and increased MDA and LDH. All these effects were inverted with overexpression of ZEB1. Conclusion: Altogether, the findings suggested that the up-regulation of miR-199a-3p significantly inhibited NSCLC growth in vivo, and reduced A549 cell proliferation and promoted mitochondrial-mediated apoptosis, through down-regulation of ZEB1. The findings supported ZEB1 down-expression with miR-199a-3p as a novel therapeutic target for NSCLC treatment. [ABSTRACT FROM AUTHOR]

In the U.S., since the 2000s, with the strong growth of China's economy and military, China has become a threat to U.S. interests in the Indo-Pacific region. Due to a breakthrough in U.S.-India relations has pushed Washington to devote more attention to this region, President Obama articulated the concepts of "pivot" or "rebalance" to Asia, and Secretary of State Hillary Clinton published an article in 2011 ("America's Pacific Century"), in which she argued that the U.S. would build a multipronged approach of military cooperation, diplomatic engagement, and free trade negotiation to establish its position in the Indo-Pacific region. [ABSTRACT FROM AUTHOR]

This paper develops a Hamiltonian state space approach for analytic determination of deformation and stress fields in multilayered monoclinic angle-ply laminates under the combined action of extension, bending, and torsion. The present solution satisfies the equations of anisotropic elasticity, the end conditions, the traction-free boundary conditions on the four edge surfaces of the rectangular section, and the interfacial continuity conditions in multilayered laminates. The proposed method only requires the solutions of matrix and eigen equations, regardless of the number or lamination of the layers. The finite element analyses are used to validate the accuracy of the analysis. The analytical solution and the numerical solutions are in excellent agreement. [ABSTRACT FROM AUTHOR]

Proper amounts of copper supplemented in livestock feed improve the physical growth and traits of farm animals. The pancreas is an important organ with both exocrine and endocrine portions. To investigate the role and mechanism of copper in the sheep pancreas, we first established sheep pancreatic duct organoids (sPDOs). We found that an appropriate amount of copper benefited the formation and growth of sPDOs, whereas excess or deficient copper damaged sPDOs. We found that the proliferation-stimulating effect of copper was related to the copper chaperone antioxidant protein 1 (ATOX1)-dependent activation of MEK-ERK1/2 signaling. Atox1 knockdown suppressed the cell proliferation of sPDOs, even in the presence of the MEK activator. These results indicate that moderate concentrations of copper promote sPDO growth through ATOX1-regulated cell proliferation by activation of MEK-ERK. Moreover, our study indicates that organoids may be a useful model to study organ growth mechanisms in livestock. [ABSTRACT FROM AUTHOR]

We developed ultrathin dual-mesoporous polymer nanosheets by combining co-assembly of different templates with in situ synthesis of functional polymers, which featured inherent smaller and template-directed larger mesopores (2.6 nm and 15 nm, respectively), ultrathin nanolayers (20 nm), high surface area (268 m2 g−1), intrinsic fluorescent properties and effective detectability for organophosphates. [ABSTRACT FROM AUTHOR]

Alopecia areata (AA) is thought to be an autoimmune process. In other autoimmune diseases, the innate immune system and Toll‐like receptors (TLRs) can play a significant role. Expression of TLR7, TLR9 and associated inducible genes was evaluated by quantitative PCR in peripheral blood mononuclear cells (PBMCs) from 10 healthy individuals and 19 AA patients, categorized according to disease duration, activity and hair loss extent. Microdissected scalp biopsies from five patients and four controls were also assessed by quantitative PCR and immunohistology. TLR9 was significantly upregulated 2.37 fold in AA PBMCs. Notably, TLR9 was most significantly upregulated in patients with active AA, as shown by a positive hair pull test, compared to stable AA patients. In hair follicle bulbs from AA patients, IFNG and TLR7 exhibited statistically significant 3.85 and 2.70 fold increases in mRNA, respectively. Immunohistology revealed TLR7 present in lesional follicles, while TLR9 positive cells were primarily observed peri‐bulbar to AA affected hair follicles. The increased expression of TLR7 and TLR9 suggest components of the innate immune system may be active in AA pathogenesis. [ABSTRACT FROM AUTHOR]

The development and demonstration of a high-bandwidth two-color temperature sensor for high-pressure environments using intensity-modulation spectroscopy (IMS) is presented. The sensor utilized rapid intensity modulation, beam coalignment, and frequency multiplexing to deal with common challenges for laser absorption spectroscopy systems at high pressures and achieved a sensor bandwidth of 100 kHz. The P(16) and R(6) transitions of the H 2 O fundamental antisymmetric stretch rovibrational band near 2.5 μ m were chosen for initial development of this temperature diagnostic concept. Temperature validation experiments were conducted with shock tubes for both reactive and non-reactive environments. Shock tube experiments were first conducted with H 2 O and N 2 mixtures at pressures of around 8.2 atm, yielding temperature measurements with a standard deviation of 2.9 K within the steady-state test time. The performance of this system was then validated at 36.9 atm, yielding temperature measurements with a standard deviation of 8.4 K . By comparing the measured temperatures with calculated temperatures based on ideal shock jump relations, the sensor achieved an average accuracy within 4.3 K of the known temperatures across multiple experiments spanning a range of 1030–1450 K, 8–38 atm. These results demonstrate that the IMS-based sensor enables high-precision measurements of temperature at high pressures. [ABSTRACT FROM AUTHOR]

Background: Wake-up stroke (WUS) accounts for up to 25% of all new ischemic strokes, but debate exists regarding whether WUS differs from non-WUS in previous studies. Our study aimed to investigate the proportion of WUS cases and to examine differences in clinical characteristics and outcomes in these two groups. Methods: Data from acute ischemic stroke patients who presented to the First Affiliated Hospital of Chongqing Medical University between April 2017 and September 2017 were prospectively collected. Admission demographic information, clinical and radiological characteristics, and 3-month functional outcomes were assessed and compared between patients with WUS and those with non-WUS. Poor functional outcome was defined as modified Rankin Scale ≥ 3 at the 90-day follow-up. Risks of poor outcomes for WUS were estimated with logistic regression analysis. Results: A total of 473 eligible patients were included, of which 132 had been diagnosed with WUS (27.9%). Forty WUS patients had poor functional outcomes and 92 WUS patients had good functional outcomes. WUS and non-WUS patients were similar in regard to stroke risk factors, severity, etiology, and prognosis at 90 days (p > 0.05), but WUS patients were more likely to have had previous stroke (p < 0.001) and a tendency of higher albumin levels (p = 0.051). WUS patients show significant differences in terms of age, gender, prior stroke, atrial fibrillation, impaired consciousness at admission, levels of albumin and triglycerides, stroke severity, and stroke etiology between the good outcome group and the poor outcome group (p < 0.05). Multivariate logistic regression analysis showed that age (odds ratio [OR] 1.079, 95% confidence interval [CI] 1.021–1.141; p < 0.05), previous stroke (OR 4.017, 95% CI 1.197–13.484; p < 0.05), and admission National Institutes of Health Stroke Scale (NIHSS) score ≥5 (OR 5.453, 95% CI 1.510–19.696; p < 0.05) were independently associated with an unfavorable outcome of WUS. Conclusions: WUS accounts for 27.9% of 473 ischemic strokes in the Chinese population. WUS and non-WUS patients were similar in terms of stroke risk factors, severity, etiology, and early outcomes. Age, previous stroke, and a high admission NIHSS score were independent risk factors for unfavorable outcomes in patients with WUS. [ABSTRACT FROM AUTHOR]

Background: Surrogates often do not accurately predict older people's preferences about end-of-life (EOL) care. Few studies have examined the impact of advance care planning (ACP) on EOL decision-making consistency between older people and their surrogates, and these studies have yielded conflicting results. Objectives: To evaluate the effectiveness of ACP in improving EOL decision-making consistency between older people and their surrogates. Design: The intervention in this pre–post quasi-experimental design included an informative video, a brochure about ACP, and a guided discussion about EOL wishes. Setting: Two geriatric wards in a medical center in northern Taiwan. Subjects: One hundred eight participants, as 54 pairs of older people and their surrogates, were randomly assigned to either the experimental or control group. The experimental group received an intervention, while the control group received usual care. Measurements: Life-Support Preferences Questionnaire. Results: The intervention did not improve decision-making consistency between older people and their surrogates. This was the first time that most pairs discussed specific EOL decisions, so additional preparation may improve comfort with this topic. This study also found that some older people had difficulty concentrating on the educational brochure or understanding the related terms. Conclusions: Preparation for ACP discussion is needed for older people and their surrogates. Longer-term effects of ACP should be monitored because ACP interventions may have enhanced empathy between older people and their surrogates. Additionally, a culturally sensitive illustrated questionnaire that explains life-support preferences and ACP topics may improve communication between older people and their surrogates. [ABSTRACT FROM AUTHOR]

Background: Physical violence against women is a major public health problem in African countries; however, no studies have focused on factors associated with violent injuries to women in Africa.Objectives: A matched case-control study was conducted to investigate risk factors for injuries from physical violence against African women in The Gambia.Methods: Over a 12-month study period, study participants were recruited from emergency departments of eight government-managed health care facilities. Cases were female patients aged ≥ 15 years who had been violently injured. Matched by the health facility, date of injury, sex, and age, a control patient for each case was selected from those injured due to nonviolent mechanisms.Results: In total, 194 case-control pairs were recruited. Results of a conditional logistic regression showed that being a Fula (odds ratio [OR] 2.45; 95% confidence interval [CI] 1.06-5.66), living in an extended family compound (OR 3.07; 95% CI 1.22-7.72), having six or more female siblings (OR 3.10; 95% CI 1.38-6.97), having been raised by grandparents (OR 3.34; 95% CI 1.06-10.51), and having been verbally (OR 3.04; 95% CI 1.56-5.96) or physically abused (OR 3.36; 95% CI 1.34-8.39) in the past 12 months were significantly associated with injury from physical violence.Conclusion: Most risk factors identified for violent injury among African women are unique to the studied geography. Violence prevention programs, if designed based on these identified risk factors, may be more effective for this population. [ABSTRACT FROM AUTHOR]

The poorly conductive organic layers in two-dimensional (2D) perovskites create quantum wells, which hinder the carrier separation and transformation. Therefore, the search for new 2D hybrid lead-halide materials with conductive organic components is crucial to high performance 2D perovskite solar cells. Tetrathiafulvalene (TTF) and its derivatives are well-known building blocks for conductive organic materials. We report here a new compound containing TMT–TTF (tetrakis(methylthio)tetrathiafulvalene) and layered PbI2, formulated as (TMT–TTF)[Pb2.6/3□0.4/3I2]3 (1). Crystal structural analysis shows that compound 1 is a unique TMT–TTF-intercalated 2D hybrid lead iodide with partially oxidized TMT–TTF cations and Pb-vacancy in anion. Its structural characteristics give the compound a narrow band gap and high conductivity. Furthermore, the carrier density and the photoelectric properties are first evaluated for TTF-PbI compounds and the results show that these properties of 1 are superior to those of the previously reported TTF-PbI salt, which is attractive for exploiting new lead-halide materials. [ABSTRACT FROM AUTHOR]

The recently introduced wavelength-modulation spectroscopy with 1f-phase detection (WMS- θ 1 f ) technique showed promising results with potentially improved measurement precision over the popular 1f-normalized WMS-nf (WMS-nf/1f) technique. Like WMS-nf/1f, WMS- θ 1 f enjoys the typical benefits of WMS methods, including low-frequency noise rejection, correction for non-absorbing losses, and insensitivity to the broadband absorption spectra of interfering species. In this work, we performed a detailed analysis of the spectrally resolved scanned-wavelength WMS- θ 1 f measurement technique and its direct comparison against the expected performance of scanned-wavelength WMS-nf/1f and scanned-wavelength direct-absorption spectroscopy (SDAS) measurements. This simulation-based analysis identified specific operating regimes in which the performance of WMS- θ 1 f measurements in terms of accuracy is expected to be greater than the performance of WMS-nf/1f or SDAS. Additionally, improved guidelines for the optimal selection of laser-tuning parameters, including an explicit optimization of the optical scan depth parameter, were developed. Experiments with a CO2 static cell perturbed by a high-speed air jet corroborated the simulation-based findings. Finally, a practical demonstration of a WMS- θ 1 f sensor for measuring temperature and H2O mole fraction in the exhaust of a CH4/air flat-flame burner was presented, with the results confirming model predictions of the superior precision of WMS- θ 1 f relative to WMS-nf/1f and SDAS. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are small noncoding single-stranded ribonucleic acid molecules. This type of endogenous oligonucleotide could be secreted into the circulation and exist stably. The detection of specific miRNAs released by cancer cells potentially provides a noninvasive means to achieve early diagnosis and prognosis of cancers. However, the typical concentration of miRNAs in blood is below the ultratrace level. This study uses a simple thermoplastic microfluidic concentration device based on an ion concentration polarization mechanism to perform enrichment and cleanup and Raman sensing beads to determine miRNA quantitatively. One sample solution containing target miRNA molecules having been hybridized with two nucleotide probes, where one probe is on a Raman tag of a nanoaggregate embedded bead (NAEB) and the other probe is on a magnetic nanoparticle (MNP), is first filled into the device. When an external field is applied across a cation exchange membrane stationed in the middle conduit of the device, the MNP-miRNA-NAEB complexed particles are enriched near the membrane edge of the cathode side. The concentrated complexed particles are further trapped using an external magnet to perform washing steps to remove excess noncomplexed NAEBs. When cleanup steps are accomplished, the remaining complexed particles are loaded into one detection capillary to acquire Raman signals from the sensing beads. Compared with that using a conventional magnetic trapping device, the cleanup time is shortened from nearly an hour to less than 10 min. Sample loss during the washing steps becomes more controllable, resulting in adequate standard curve linearity (R > 0.99) ranging from 1 to 100 pM. [ABSTRACT FROM AUTHOR]

As the number of breast cancer survivors increases, these patients with sexual problems also increase. For breast cancer survivors, sexual problems are a common and painful experience. Although breast cancer survivors often encounter sexual problems, Taiwanese women are culturally conservative and patients rarely discuss sex problems with clinicians. In this study, we used qualitative methods to better understand the changes in sexual life and related care strategies for breast cancer survivors. Twenty interviews were conducted on clinical patients enrolled in hospitals that received breast cancer treatment. The data were analysed by performing a constant comparative analysis. Three themes emerged: the causes of changes in sexual life, internal response strategies and external response strategies. Ten subthemes were identified. Changes in sexual life in patients with breast cancer in this study included changes related to body image, influence of friends and family, age, genital problems, and illegal love of a partner. Breast cancer survivors can tolerate and regulate sexual life changes by adopting internal and external response strategies. Medical staff must be sensitive and must understand strategies for dealing with sexual life changes that may occur during cancer adjustment and how these strategies can help women's well-being in the rest of their lives. [ABSTRACT FROM AUTHOR]

The stigma (tip of the pistil) of medlar is wet and covered with stigmatic exudate at anthesis. The exudate contains many vesicles with abundant calcium precipitates. After deposition on the stigma, the pollen grain undergoes hydration, displaying signs of calcium ion (Ca2+) transfer from the exudate vesicles into the pollen grains. Calcium precipitates in the pollen cytoplasm are concentrated into small vacuoles that fuse to form large vacuoles, which provide turgor pressure to push the cytoplasm to the apical region of the growing pollen tube. Many calcium precipitates are present in the stylar transmitting tract, which displays a calcium gradient: fewer precipitates are localised in the distal (upper) transmitting tissue below the stigma, and more precipitates are present in the transmitting tract at the style base. The emporal and spatial distribution of calcium in the stigma and style of medlar suggests that it satisfies the demand for calcium in vivo and played some functional significance. [ABSTRACT FROM AUTHOR]

Aims: To test whether fractures and osteoporosis are more prevalent among patients with opioid use disorder (OUD) than patients without OUD in Taiwan. Design We conducted a retrospective cohort study using data from the National Health Insurance Research Database (NHIRD) in Taiwan. Setting: Taiwan. Participants: The number of adult patients with OUD and without OUD was 3695 and 14 780, respectively. We established both cohorts from 1 January 1998 to 31 December 2011 to observe the incidence of fracture. The occurrence of fracture was followed‐up until the end of 2011. Measurements The primary measure was incidence of fracture. The relative risk of fracture was estimated using the Cox proportional hazard model after adjusting for age, sex, index year and comorbidities. Comorbidities included diabetes mellitus, hyperlipidemia, stroke, chronic obstructive pulmonary disease, heart failure, alcohol‐related illness, osteoporosis, end‐stage renal disease, obesity and rheumatoid arthritis, using the International Classification of Diseases, 9th revision, clinical modification. Findings Patients with OUD were 4.13 times more likely to suffer fractures than patients without OUD [incidence rate (IR) per 1000 person‐years = 23.0 versus 5.47, adjusted hazard ratio (HR) = 3.74, 95% confidence interval (CI) = 3.27–4.29]. Compared with the control group, the risk of fracture was higher among the patients with OUD. Risk of fracture was higher in male elderly patients with diabetes mellitus, alcohol‐related illness or osteoporosis. The cumulative incidences of fracture over 14 years of patients with OUD and without OUD differed significantly. Conclusions: Taiwanese patients with opioid use disorder appear to have a higher adjusted hazard ratio for fracture than Taiwanese patients without opioid use disorder. [ABSTRACT FROM AUTHOR]

Rationale and objective: The presence of three conspecifics prevents stress-induced decreases in newly proliferated cells and neuroblasts in mouse dentate gyrus (DG). In this study, we sought to determine how many conspecifics are required to exert these protective effects against stress. In addition, we manipulated the physiological status of those conspecifics in the context of their stress-buffering effects and used airborne oxytocin exposure as a substitute for the presence of conspecifics. Materials and methods: Bromodeoxyuridine staining was used to indicate the newly proliferated cells and co-staining with doublecortin to reveal the proliferative neuroblasts. Results: Presentation of three intact and lipopolysaccharide-treated conspecifics prevented the stress-induced decreases in the number of newly proliferated cells and neuroblasts in DG. Presentation of one saline- or oxytocin (OT)–treated conspecific did not exert observable stress-buffering effects. In contrast, airborne oxytocin prevented the stress-induced decreases in DG cell proliferation and early neurogenesis, while pretreatment with L-371,257, a selective OT receptor antagonist, abolished the buffering effects of OT. Conclusions: Physical interaction with the conspecifics and conspecifics' sickness, at best, play a minor role in mediating the buffering effects against stress-induced decreases in DG cell proliferation or early neurogenesis. Moreover, stress-buffering effects are negligible with the presence of only one conspecific. Finally, airborne OT produced stress-buffering effects possibly via its stimulation of OT receptors. Oxytocin merits further study as a substitute for the stress-buffering effects of companions. [ABSTRACT FROM AUTHOR]

Mode shapes estimated from the vehicle responses are normally used to detect bridge damage efficiently for their high spatial resolution. However, an updated baseline finite element model (FEM) is normally required to quantify damages for such an approach. A two-stage damage detection procedure is presented for bridges by utilizing the mode shape estimated from a moving vehicle. Damage locations are first determined through a damage localization index (DLI) defined by regional mode shape curvature (RMSC). Then the relationship between the damage extents and the RMSC changes is investigated by FEM simulation. Finally, an equation set to quantify the single and multiple damages is deduced by combining the RMSCs and the relationship between the damage extents and the RMSC changes established by an un-updated FEM. Numerical and experimental examples are carried out to verify the validity and efficiency of the two-stage method. The results revealed that it can localize and quantify damages with satisfactory precision by using the response measured from one sensor only. [ABSTRACT FROM AUTHOR]

Technological facilities and services have become attractive features in hotel selection. However, limited research has been conducted on how technological innovation attributes are perceived by hotel tourists. This paper aims to highlight and categorize the technological innovation attributes of hotels based on the Kano model. Empirical testing shows four technological innovation factors: Internet and app usage, smartphone usage as a room key and for payment, E-housekeeping, and the use of electronic self-service systems. Findings provide practical implications for hotel operators planning to introduce technologies into their hotels. [ABSTRACT FROM AUTHOR]

BACKGROUND: Golgi phosphoprotein 3 (GOLPH3) is a novel oncogene overexpressed in several human cancers, but specific contributions to endometrial carcinoma (EC) have not been examined. The aims of this study were to evaluate the GOLPH3 expression in EC and investigate its functions in EC cell proliferation, migration, and survival. METHODS: The expression levels of GOLPH3 in EC patient samples and EC cell lines (HEC-1A, KLE, RL95-2, and Ishikawa) were examined using qRT-PCR, western blotting and immunohistochemistry. Further, EC cell lines with either ectopic GOLPH3 overexpression or knockdown were established, and the effects on proliferation, apoptosis, invasion, and migration were investigated in vitro using cell viability and transwell assays and in mice following cell injection. RESULTS: Compared to adjacent non-cancerous tissues, expression of GOLPH3 was significantly upregulated in EC tissues (P < 0.05), and the expression level of GOPLPH3 was related to the grade of the tumor (P < 0.05). The expression of GOLPH3 was also higher in all four EC cell lines than endometrial stromal cells (ESCs) (P < 0.05). Moreover, GOLPH3 expression was greater in EC cell lines with high invasive capacity than in non-invasive EC cells (P < 0.05). Knockdown of GOLPH3 inhibited EC cell proliferation and increased cell apoptosis in vitro. Further, knockdown of GOLPH3 also inhibited EC cell invasion and migration in vitro and in vivo by regulating the epithelial-mesenchymal transition (EMT). Conversely, GOLPH3 overexpression promoted proliferation and migration. CONCLUSIONS: The present study provides evidence that GOLPH3 promotes EMT and metastasis of EC cells and predicts the risk of EC progression, highlighting its potential as a therapeutic target for this malignancy. [ABSTRACT FROM AUTHOR]

Background: Adherence to rehabilitation is beneficial to patients with hip fracture. However, the relationships between different levels of adherence and postoperative recovery among older adults after hip fracture have not been addressed thoroughly in the literature. Objectives: The aims of this study were to explore the trajectories of adherence to home-based rehabilitation during the 12-month period after hospital discharge and to examine the effects of adhering to prescribed home-based rehabilitation on postoperative recovery of physical functions. Methods: We employed a secondary data analysis, and 88 hip-fractured older adults with diabetes were recruited. The Chinese Barthel Index was used to measure daily physical functions, a goniometer was used to measure range of motion, and the MicroFET2 dynamometer was used to measure muscle power. Adherence was measured as the rate of adherence to the suggested frequency of home-based rehabilitation activities. Results: Adherence to home-based rehabilitation decreased over time. The high-adherence group was more likely to recover prefracture physical functions than was the low-adherence group, and the high-adherence group had better self-care abilities, greater range of motion for ankle extension, and higher muscular strength on both adduction and abduction than did the low-adherence group. Discussion: The results of our study suggest that patients adhere to more than 50% of prescribed rehabilitation. Future studies should continue to explore interventions to enhance rehabilitation adherence after hospital discharge. [ABSTRACT FROM AUTHOR]

Radiotherapy is a common treatment option for head and neck cancer patients; however, the surrounding healthy salivary glands are often incidentally irradiated during the process. As a result, patients often experience persistent xerostomia and hyposalivation, which deceases their quality of life. Clinically, there is currently no standard of care available to restore salivary function. Repair of epithelial wounds involves cellular proliferation and establishment of polarity in order to regenerate the tissue. This process is partially mediated by protein kinase C zeta (PKCζ), an apical polarity regulator; however, its role following radiation damage is not completely understood. Using an in vivo radiation model, we show a significant decrease in active PKCζ in irradiated murine parotid glands, which correlates with increased proliferation that is sustained through 30 days post-irradiation. Additionally, salivary glands in PKCζ null mice show increased basal proliferation which radiation treatment did not further potentiate. Radiation damage also activates Jun N-terminal kinase (JNK), a proliferation-inducing mitogen-activated protein kinase normally inhibited by PKCζ. In both a PKCζ null mouse model and in primary salivary gland cell cultures treated with a PKCζ inhibitor, there was increased JNK activity and production of downstream proliferative transcripts. Collectively, these findings provide a potential molecular link by which PKCζ suppression following radiation damage promotes JNK activation and radiation-induced compensatory proliferation in the salivary gland. [ABSTRACT FROM AUTHOR]