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The kilometer square array (KM2A) of the large high altitude air shower observatory (LHAASO) aims at surveying the northern γ-ray sky at energies above 10 TeV with unprecedented sensitivity. γ-ray observations have long been one of the most powerful tools for dark matter searches, as, e.g., high-energy γ rays could be produced by the decays of heavy dark matter particles. In this Letter, we present the first dark matter analysis with LHAASO-KM2A, using the first 340 days of data from 1/2-KM2A and 230 days of data from 3/4-KM2A. Several regions of interest are used to search for a signal and account for the residual cosmic-ray background after γ/hadron separation. We find no excess of dark matter signals, and thus place some of the strongest γ-ray constraints on the lifetime of heavy dark matter particles with mass between 10^{5} and 10^{9}  GeV. Our results with LHAASO are robust, and have important implications for dark matter interpretations of the diffuse astrophysical high-energy neutrino emission.

Objective: To investigate the long-term effect of finasteride (FS) on high-risk BPH patients after treated by implantation of thermo-expandable spiral prostatic stent (TESPS)., Methods: We retrospectively analyzed the clinical data on 63 cases of BPH treated by implantation of TESPS in our Department of Urology from January 2017 to January 2019. All the patients received oral FS after operation except two cases of stent removal because of infection, 37 for more than 12 months (the long-term FS group) and the other 24 for less than 12 months (the control group). We followed up the patients at 3, 6, 12, 24, 36 and 48 months postoperatively, recorded the incidence of hematuria and infection, IPSS, maximum urinary flow rate (Qmax) and residual urine volume (PVR), and compared them between the two groups of patients., Results: At 48 months after operation, the incidence rates of postoperative hematuria and infection were significantly lower in the long-term FS group than in the control (P < 0.05), but evidently increasing with the prolonging of medication time. The total effectiveness rate was as high as 95.1% at 3 months, but only 63.6% at 48 months, significantly higher, however, in the long-term FS than in the control group (69.2% vs 55.6%, P < 0.05), and the IPSS, Qmax and PVR were also remarkably higher in the former than in the latter group (P < 0.05)., Conclusion: The long-term effect of TESPS implantation is definite in the treatment of BPH-induced dysuria, and it can be used as a first-choice method for the patients at high risk and unsuitable for surgery. Finasteride has an evident advantage in preventing hematuria and infection after prostatic stent implantation, and long-term medication of finasteride improves long-term outcomes.

In this paper, the potential energy curves of 22 Λ-S states as well as 51 Ω states were calculated using the internally contracted multiconfiguration interaction and Davidson correction method. Through the obtained transition data, the spectroscopy data of the low excitation bound state are fitted and compared with the same main group ions. The phenomenon of avoided crossing that occurs in the Ω state is analyzed, and finally it is concluded that this phenomenon mainly occurs in the energy region between 20 000 cm -1 and 40 000 cm -1 . The potential laser cooling transition cycle in the Ω state is analyzed. The Franck-Condon factor, radiative lifetime and Einstein coefficient between are calculated. In this paper, we argue that direct laser cooling of SeBr + is not feasible. The content of our study provides a theoretical basis for subsequent calculations to explore the properties of SeBr + spectrum., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Black shank disease caused by Phytophthora nicotianae is one of the most important diseases in tobacco worldwide and can result in a devastating loss in tobacco cultivation. Many efforts have been carried out to identify the chromosome segment from Nicotiana plumbaginifolia containing a resistance locus carrying a gene named Php ; however, the Php gene has not been cloned, and knowledge of the potential mechanism of the Php gene in the resistant lines is limited. To further characterize the resistance mechanism of the Php gene, we first used the resistant line "RBST" and the susceptible cultivar "Honghuadajinyuan" (HD) to obtain the near-isogenic line RBS89 containing the Php gene from RBST. RBS89 showed high resistance to black shank disease. Transcriptomic and iTRAQ analyses were applied to explore the potential defense mechanisms in RBS89 plants in comparison with HD plants with or without inoculation. Many differentially expressed genes (DEGs) and proteins were identified, and some pathogenesis-related (PR) proteins were extensively abundant in the RBS89 plants when compared with the HD plants in response to black shank disease. Importantly, overexpression of the PR gene NtPR-1B in HD plants improved the resistance of tobacco plants to black shank disease, indicating that NtPR-1B and Php genes might have similar roles in protecting tobacco from black shank disease. However, the relationship between NtPR-1B and Php genes requires further analysis. Therefore, our study provides valuable information for breeding tobacco cultivars with black shank disease resistance and sheds light on the defense mechanism of black shank disease in tobacco for enhancing Phytophthora resistance in other Solanaceae crops., Competing Interests: Author J-LG was employed by Lincang Company of Yunnan Tobacco Company. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bai, Fang, Yang, Tong, Chen, Fei, Gong, Xie and Xiao.)

Loving-kindness meditation (LKM) was first practiced by Buddhists and then developed by clinical psychologist. Previous studies on LKM have mainly focused on the impact of real person-guided meditation on depression, anxiety, and other negative psychology. During the COVID-19 pandemic, this study explored the effect and mechanism of media-guided LKM on the improvement of social presence, mindfulness, spirituality, and subjective wellbeing (SWB). From the viewpoint of positive psychology, this study compared the different media effects of animated pedagogical agent (APA)-guided LKM and audio-guided LKM. A total of 82 flight attendants were recruited from airlines; then, they were randomly assigned to two groups: APA group (41 participants) and audio group (41 participants), which both underwent an 8-week LKM training intervention. The aforementioned four main variables were measured pre and post the meditation experiment. The results indicated that both APA-guided meditation and audio-guided meditation significantly improved subjects' spirituality and SWB. Compared with audio-guided meditation, APA-guided meditation significantly improved the subjects' spirituality, SWB, and social presence. Audio-guided meditation has no significant effect on social presence. This study highlights APA-guided meditation has a positive effect on spirituality, SWB, and social presence, which may provide individuals with a simple and easy method to improve their mental health., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Chen, Zhou, Chiang, Chen, Wu, Huang, Liu and Chiou.)

Previous studies on parenting adult children with ASD were scarce, and their intervention protocols mainly were derived from established work with children. Development of an applicable adult-oriented protocol and demonstration of its effectiveness is warranted. The present study outlined the development and evaluation of Core Autism Parenting Skills (CAPS), which targets to enhance parenting self-efficacy (PSE) intervention for adult children with ASD by addressing two intervention goals in parallel: acquisition of parenting skills and cultivating positive attributes. In CAPS, PSE is operationalised into four parent roles: to observe, reinforce, empathise, and accompany, each with requisite attributes, skills, and prescribed training. Twenty-seven parents with adult children with ASD (aged 16-37) were recruited. They completed measures assessing their PSE, competence in the four parent roles, and emotional well-being at pre-training, post-training and 2-month follow-up. The intervention was well-received by the participants and reported significant improvements in PSE, parent role competence at post-training and 2-month follow-up. The applicability of PSE and parent role competence in constructing effective parenting intervention for adult children with ASD was supported., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Leung, Tsang, Huang and Chan.)

Background: This study investigated the effects of the loving-kindness meditation (LKM) on employees' mindfulness, affect, altruism and knowledge hiding., Methods: In total, 100 employees were recruited from a knowledge-based enterprise in China and randomly divided into the LKM training group (n = 50) and the control group (n = 50). The LKM training group underwent LKM training for 8 weeks, while the control group did not. Seven main variables (mindfulness, altruism positive affect, negative affect, playing dumb, rationalized hiding, and evasive hiding) were measured both before (pre-test) and after (post-test) the LKM training intervention., Results: The LKM intervention significantly increased participants' altruism, and significantly reduced negative affect, playing dumb and evasive hiding, but did not significantly improve mindfulness, positive affect, and rationalized hiding., Conclusions: LKM significantly improved employees' altruism, and significantly reduce their negative affect, but did not significantly improve their mindfulness and positive affect. For knowledge hiding, LKM significantly reduced playing dumb and evasive hiding, but had no significant effect on rationalized hiding. These results further elucidate the psychological effects of LKM and suggest the possibility of reducing knowledge hiding in the workplace., Trial Registration: ChiCTR2200057460. Registered in Chinese Clinical Trial Registry (ChiCTR), 13 March 2022-Retrospectively registered., (© 2022. The Author(s).)

The electronic conductive metal-organic frameworks (EC-MOFs) based on a single ligand are not suitable for the accurate detection of bisphenol A (BPA) due to the limitations of their electron-transfer-based sensing mechanism. To overcome this drawback, we developed EC-MOFs with novel dual-ligands, 2,3,6,7,10,11-hexahydroxy-sanya-phenyl (HHTP) and tetrahydroxy 1,4-quinone (THQ), and metal ions. A new class of 2D π-conjugation-based EC-MOFs (M-(HHTP)(THQ)) was synthesized by a self-assemble technique. Its best member (Cu-(HHTP)(THQ)) was selected and combined with reduced graphene (rGO) to form a Cu-(HHTP)(THQ)@rGO composite, which was thoroughly characterized by X-ray diffraction, field scanning electron microscopy, and energy-dispersive X-ray spectroscopy. Cu-(HHTP)(THQ)@rGO was drop-cast onto a glassy carbon electrode (GCE) to obtain a sensor for BPA detection. Cyclic voltammetry and electrochemical impedance tests were used to evaluate the electrode performance. The oxidation current of BPA on the Cu-(HHTP)(THQ)@rGO/GCE was substantially higher than on unmodified GCE, which could be explained by a synergy between Cu-(HHTP)(THQ) (which provided sensing and adsorption) and rGO (which provided fast electron conductivity and high surface area). Cu-(HHTP)(THQ)@rGO/GCE exhibited a linear detection range for 0.05-100 μmol·L -1 of BPA with 3.6 nmol·L -1 (S/N = 3) detection limit. We believe that our novel electrode and BPA sensing method extends the application perspectives of EC-MOFs in the electrocatalysis and sensing fields.

Creativity is so important for social and technological development that people are eager to find an easy way to enhance it. Previous studies have shown that mindfulness has significant effects on positive affect (PA), working memory capacity, cognitive flexibility and many other aspects, which are the key to promoting creativity. However, there are few studies on the relationship between mindfulness and creativity. The mechanism between mindfulness and creativity is still uncertain. Meditation is an important method of mindfulness training, but for most people who do not have the basic training, it's difficult to master how to get into a state of mindfulness. Animation has been shown by many studies to help improve cognition and is often used as a guiding tool. Using animation as the guiding carrier of meditation is more convenient and easier to accept. Therefore, this study adopted the intervention method of animation-guided meditation, aiming to explore: (1) the effect of animation-guided meditation on enhancing creativity; (2) the role of flow and emotion in the influence of mindfulness on creativity. We advertised recruitment through the internal network of a creative industrial park, and the final 95 eligible participants were divided into two groups: animation ( n  = 48) and audio ( n  = 47) guided meditation. The animation group was given an animated meditation intervention, and the audio group was given an audio meditation intervention, both interventions were performed 3 times a week and last for 8 weeks. Results: (1) Animation-guided meditation significantly increased participants' mindfulness and creativity levels; Significantly reduced their cognitive load compared to audio-guided meditation. (2) Mindfulness has a significant direct effect on creativity, and significant indirect effects on creativity; Flow and PA act as the mediating variable. Conclusion: (1) Mindfulness, flow, and PA all helped to improve the subjects' work creativity. In addition to the direct positive impact of mindfulness on creativity, mindfulness can also have an indirect positive impact on creativity through flow and PA. (2) Compared with audio, animation can significantly reduce cognitive load and help improve users' cognitive ability, which is more suitable for the guidance materials of mindfulness meditation to enhance the effect of meditation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Liu, Zhou, Chiang, Chen, Wu, Huang, Liu and Chiou.)

Little is known about the effectiveness of Interdisciplinary teaching (IDT) in higher education, particularly for healthcare education in Taiwan. It is vital to determine if IDT could enhance divergent creative thinking and team creativity among nursing students. A quasi-experimental study with a pretest-posttest design. Students enrolled in a capstone nursing course for the development of healthcare-related products were divided into two groups. The intervention group ( n = 61) was taught creative thinking skills with IDT by faculty. The control group ( n = 84) was taught by nursing faculty with traditional teaching. This study found that students who received the IDT intervention scored significantly higher on measures of creative thinking and team creativity compared with students in the control group. These findings suggest integrating IDT from nursing and design faculty into the teaching curriculum to foster students' creative thinking abilities when formulating interdisciplinary student teams to develop innovative, creative healthcare products.

Bronchial asthma (asthma) is one of the most common chronic airway diseases, with more than 300 million people worldwide suffering from this disease. In recent years, studies have shown that compared with healthy people, the airway microecological structure and relative abundance of various flora of asthmatic patients have changed, and are related to the airway inflammatory phenotype of asthma. Airway microecology can affect the occurrence and development of asthma through immune response. The mechanism of interaction between airway microecology and asthma can provide new ideas for the accurate treatment of asthma. This article mainly reviewed the current research on airway microecology in asthma, and puts forward prospects for the accurate treatment of asthma in the future.

Objective: Patient safety is a worldwide problem and a focus of academic research. Human factors and ergonomics (HFE) is an approach to improving healthcare work systems and processes. From the perspective of the cognitive ergonomics of HFE, the aim of this study is to improve the flow level, communication skills, and safety attitudes of surgeons through focused-attention meditation (FAM) training, thus helping to reduce adverse clinical events., Methods: In total, 140 surgeons were recruited from three hospitals in China and randomly divided into two groups (FAM group and control group). The FAM group received 8 weeks of FAM training, while the control group was on the waiting list and did not receive any interventions. Three scales (WOLF, LCSAS, and SAQ-C) were used to measure the data of three variables (flow, communication skills, and safety attitude), respectively, at two times, before and after the intervention (pre-test and post-test). The incidence of adverse events during the intervention was also collected for both groups., Results: The ANOVA results showed that all three variables had a significant main effect of time and significant interactions between time and group. The independent-sample T-test results showed that the incidence of adverse events during the intervention was significantly lower in the FAM group than in the control group., Conclusions: The intervention of FAM could significantly improve surgeons' flow levels, communication skills, and safety attitudes, potentially helping to reduce adverse clinical events.

Objective: This study investigated the effects of mindfulness meditation on doctors' mindfulness, patient safety culture, patient safety competency, and adverse events., Methods: We recruited 91 doctors from a hospital in China and randomized them to mindfulness meditation group ( n = 46) and a waiting control group ( n = 45). The mindfulness meditation group underwent an 8-week mindfulness meditation intervention, while the control group underwent no intervention. We measured four main variables (mindfulness, patient safety culture, patient safety competency, and adverse event) before and after the mindfulness meditation intervention., Results: In the experimental group, mindfulness, patient safety culture and patient safety competency were significantly higher compared with those of the control group. In the control group, there were no significant differences in any of the three variables between the pre-test and post-test. Adverse events in the experimental group were significantly lower than in the control group., Conclusions: The intervention of mindfulness meditation significantly improved the level of mindfulness, patient safety culture and patient safety competency. During the mindfulness meditation intervention, the rate of adverse events in the meditation group was also significantly lower than in the control group. As a simple and effective intervention, mindfulness meditation plays a positive role in improving patient safety and has certain promotional value.

Background: Accumulating studies have suggested the airway microbiota in lung cancer patients is significantly different from that of healthy controls. However, little is known about the relationship between airway microbiota and important clinical parameters of lung cancer. In this study, we aimed to explore the association between sputum microbiota and lung cancer stage, lymph node metastasis, intrathoracic metastasis, and epidermal growth factor receptor (EGFR) gene mutation., Methods: The microbiota of sputum samples from 85 newly-diagnosed NSCLC patients were sequenced via 16S rRNA sequencing of the V3-V4 region. Sequencing reads were filtered using QIIME2 and clustered against UPARSE., Results: Alpha- and β-diversity was significantly different between patients in stages I to II (early stage, ES) and patients in stages III to IV (advanced stage, AS). Linear discriminant analysis Effect Size (LEfSe) identified that genera Granulicatella and Actinobacillus were significantly enriched in ES, and the genus Actinomyces was significantly enriched in AS. PICRUSt2 identified that the NAD salvage pathway was significantly enriched in AS, which was positively associated with Granulicatella. Patients with intrathoracic metastasis were associated with increased genus Peptostreptococcus and incomplete reductive TCA cycle, which was associated with increased Peptostreptococcus. Genera Parvimonas, Pseudomona and L-valine biosynthesis were positively associated with lymph node metastasis. L-valine biosynthesis was related with increased Pseudomona. Finally, the genus Parvimonas was significantly enriched in adenocarcinoma patients with EGFR mutation., Conclusion: The taxonomy structure differed between different lung cancer stages. The tumor stage, intrathoracic metastasis, lymph node metastasis, and EGFR mutation were associated with alteration of specific airway genera and metabolic function of sputum microbiota., (© 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Recently, the LHAASO Collaboration published the detection of 12 ultrahigh-energy γ-ray sources above 100 TeV, with the highest energy photon reaching 1.4 PeV. The first detection of PeV γ rays from astrophysical sources may provide a very sensitive probe of the effect of the Lorentz invariance violation (LIV), which results in decay of high-energy γ rays in the superluminal scenario and hence a sharp cutoff of the energy spectrum. Two highest energy sources are studied in this work. No signature of the existence of the LIV is found in their energy spectra, and the lower limits on the LIV energy scale are derived. Our results show that the first-order LIV energy scale should be higher than about 10^{5} times the Planck scale M&#95;{Pl} and that the second-order LIV scale is >10^{-3}M&#95;{Pl}. Both limits improve by at least one order of magnitude the previous results.

Purpose: To assess the relationship between serum/follicular fluid (FF) vitamin D (VD) status and assisted reproductive technology (ART) treatment outcomes among infertile patients., Methods: A prospective cohort study, including 132 infertile patients scheduled for their first ART treatment cycle, was carried out in a Reproductive Medical Center. Serum and FF samples were collected to assess 25-hydroxy VD [25(OH)D] levels. Low VD level was defined as 25(OH)D concentration of less than 30 ng/mL., Results: Most infertile patients had low VD levels in serum (88%) and FF (90%). We observed a moderately positive correlation between VD levels in serum and FF (r = 0.34, p < 0.0001). Compared to the group of patients with low VD levels in the FF, those with sufficient VD levels had a significantly higher number of retrieved oocytes (p = 0.03), normal fertilization (p = 0.01), and high-quality embryos (p = 0.001). Moreover, patients with sufficient VD levels in the FF also had significantly higher implantation rates than those with low VD levels (76.92% vs. 46.58%, respectively, p = 0.01) and clinical pregnancy rates (92.31% vs. 61.54%, respectively, p = 0.04)., Conclusion: These data collectively revealed that low VD levels in serum and FF were common among infertile patients. VD levels in FF, but not in serum, were associated with embryo quality, normal fertilization, implantation rates, and clinical pregnancy rates. Further studies are mandatory to determine the molecular mechanism and VD's potential therapeutic benefits in infertile patients., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The use of cortical strut allograft has not been determined for Vancouver type B1 or C fracture. This study aimed to evaluate the short-term efficacy of locking compression plating with or without cortical strut allograft in managing these types of fractures., Methods: We retrospectively assessed 32 patients (17 males, 15 females; 23-88 years, mean: 67.2 years) with Vancouver type B1 or C fractures. Seventeen patients (Group A; B1 fractures in 15 hips, C fractures in 2 hips) were treated with open reduction and internal fixation with locking compression plates (group A). The other 15 patients (Group B; B1 in 14 hips, C in 1 hip) were fixed by locking compression plating combined with cortical strut allografting (group B). The fracture healing rate, healing time, complications and function were compared between these two groups., Results: The mean follow-up time was 32.4 months (12 to 66), and the overall fracture union rate of the 32 patients was 96.9%. Group B had a higher fracture union rate than Group A, but the difference was not statistically significant. Group A had one case of nonunion of type B1 fracture and one case of malunion; the mean time to fracture healing was 5.3 months (3 to 9). In group B, all patients reached bony union without malunion, with a mean time of fracture healing of 5.1 months (3 to 8)., Conclusion: Treatment of Vancouver type B1 or C fractures by locking compression plating, with or without cortical strut allografting, resulted in similar union rates in these patients. This suggest that, the use of cortical strut allografting should be decided cautiously., (© 2022. The Author(s).)

Lactic acid (LA) metabolism in the tumor microenvironment contributes to the establishment and maintenance of immune tolerance. This pathway is characterized in tumor associated macrophages. However, the role and pathway of LA metabolism at maternal-fetal interface during early pregnancy, especially in decidual macrophage differentiation, are still unclear. Herein, for the first time, we discovered that LA can trigger either M2 or M1 macrophage polarization via oxidative phosphorylation and glycolysis regulation under normoxia or hypoxia, respectively. Also, LA metabolism played a vital role in decidual macrophages-mediated recurrent pregnancy loss (RPL), through HIF-1α/SRC/LDHA pathway. Moreover, blockade of LA intake with AZD3965 (MCT-1 inhibitor) could rescue pregnancy in an abortion-prone mouse model, suggesting a potential therapeutic target in RPL. Collectively, the present study identifies the previously unknown functions of LA metabolism in the differentiation of decidual macrophages in early normal pregnancy and RPL, and provides a potential therapeutic strategy in RPL by manipulating decidual macrophages' functions through LA metabolic pathway., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The survival rate of Castanopsis kawakamii from seed to seedling is relatively low, leading to difficulties in the regeneration of its natural forests. Forest gaps play a vital role in plant regeneration and biodiversity maintenance in forest ecosystems. Unfortunately, our understanding of the effects of gap size and within-gap position on the seed germination and radicle growth of C. kawakamii is still limited. In particular, our knowledge on the relationship between gap size and environmental factors and their influence on seed germination and radicle growth is incomplete. In the present study, we studied the influences of forest gaps and within-gap position on seed regeneration on the germination and radicle growth of an endangered species C. kawakamii in a subtropical natural forest in China. We selected three large gaps (LG, gap size above 200 m 2 ), three medium gaps (MG, gap size 50-100 m 2 ), three small gaps (SG, gap size 30-50 m 2 ), and non-gap (NG), and planted the seeds of C. kawakamii in five positions within each gap. The results showed that (1) the influence of forest gaps on seed germination rate was, from highest to lowest, medium gaps (51%), non-gap (47%), small gaps (40%) and large gaps (17%), and the seed germination rate was the highest in all positions in medium gaps, with the exception of the east position. (2) Radicle length in forest gaps was, from highest to lowest, medium gaps, small gaps, large gaps and non-gap, and it was the highest in the east, south, west and north positions of medium gaps. (3) Canopy openness (gap size) and air temperature were the main factors influencing seed germination and radicle growth of C. kawakamii . We concluded that medium-sized gaps were the most suitable for seed germination and radicle growth of C. kawakamii , and they promote the regeneration of this endangered species in the investigated natural forest., Competing Interests: There are no conflicts of interest to declare., (© 2021 Kunming Institute of Botany, Chinese Academy of Sciences. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.)

Visceral obesity increases risk of cognitive decline in humans, but subcutaneous adiposity does not. Here, we report that beige adipocytes are indispensable for the neuroprotective and anti-inflammatory effects of subcutaneous fat. Mice lacking functional beige fat exhibit accelerated cognitive dysfunction and microglial activation with dietary obesity. Subcutaneous fat transplantation also protects against chronic obesity in wildtype mice via beige fat-dependent mechanisms. Beige adipocytes restore hippocampal synaptic plasticity following transplantation, and these effects require the anti-inflammatory cytokine interleukin-4 (IL4). After observing beige fat-mediated induction of IL4 in meningeal T-cells, we investigated the contributions of peripheral lymphocytes in donor fat. There was no sign of donor-derived lymphocyte trafficking between fat and brain, but recipient-derived lymphocytes were required for the effects of transplantation on cognition and microglial morphology. These findings indicate that beige adipocytes oppose obesity-induced cognitive impairment, with a potential role for IL4 in the relationship between beige fat and brain function., (© 2021. The Author(s).)

The Crab Nebula is a bright source of gamma rays powered by the Crab Pulsar's rotational energy through the formation and termination of a relativistic electron-positron wind. We report the detection of gamma rays from this source with energies from 5 × 10 -4 to 1.1 peta-electron volts with a spectrum showing gradual steepening over three energy decades. The ultrahigh-energy photons imply the presence of a peta-electron volt electron accelerator (a pevatron) in the nebula, with an acceleration rate exceeding 15% of the theoretical limit. We constrain the pevatron's size between 0.025 and 0.1 parsecs and the magnetic field to ≈110 microgauss. The production rate of peta-electron volt electrons, 2.5 × 10 36 ergs per second, constitutes 0.5% of the pulsar spin-down luminosity, although we cannot exclude a contribution of peta-electron volt protons to the production of the highest-energy gamma rays., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Background: Diffuse large B-cell lymphoma (DLBCL) is a common non-Hodgkin lymphoma. The development of immunotherapy greatly improves the patient prognosis but there are some exceptions. Thus, screening for better biomarkers for prognostic evaluation could contribute to the treatment of DLBCL patients., Aim: To screen the novel mediators involved in the development of DLBCL., Methods: The GSE60 dataset was applied to identify the differentially expressed genes (DEGs) in DLBCL, and the principal components analysis plot was used to determine the quality of the included samples. The protein-protein interactions were analyzed by the STRING tool. The key hub genes were entered into to the GEPIA database to determine their expressions in DLBCL. Furthermore, these hub gene alterations were analyzed in cBioportal. The UALCAN portal was employed to analyze the expression of the hub genes in different stages of DLBCL. The Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data Score was conducted to evaluate the correlation between the gene expression and tumor purity. The gene-gene correlation analysis was conducted in the GEPIA. The stromal score analysis was conducted in TIMER to confirm the correlation between the gene expression and infiltrated stromal cells. The correlation between the indicated genes and infiltration level of cancer-associated fibroblasts (CAFs) was also completed in TIMER with two methods, MCP-Counter and Tumor immune dysfunction and exclusion. The correlation between fibronectin (FN1) protein level and secreted protein acidic and cysteine-rich (SPARC) messenger ribonucleic acid expression was confirmed in the cBioportal., Results: The top 20 DEGs in DLBCL were identified, and the principal components analysis plot confirmed the quality of the significant DEGs. The pairwise correlation coefficient analysis among all samples showed that these DEGs have a certain co-expression pattern. The DEGs were subjected to STRING to identify the hub genes, alpha-2-macroglobulin ( A2M ), cathepsin B ( CTSB ), FN1 , matrix metallopeptidase 9 ( MMP9 ), and SPARC . The five hub genes were confirmed to be overexpressed in DLBCL. The cBioportal portal detected these five hub genes that had gene alteration, including messenger ribonucleic acid high amplification and missense mutation, and the gene alteration percentages of A2M , FN1 , CTSB , MMP9 , and SPARC were 5%, 8%, 5%, 2.7%, and 5%, respectively. Furthermore, the five hub genes had a potential positive correlation with tumor stage. The correlation analysis between the five genes and tumor purity confirmed that the five genes were overexpressed in DLBCL and had a positive correlation with the development of DLBCL. More interestingly, the five genes had a significant correlation with the stromal infiltration scores. The correlation analysis between the fives genes and CAFs also showed a significant value, among which the top two genes, FN1 and SPARC , had a remarkable co-expression pattern., Conclusion: The top DEGs were identified, and the five hub genes were overexpressed in DLBCL. Furthermore, the gene alterations were confirmed and the positive correlation with tumor purity revealed the overexpression of the five genes and close association with the development of DLBCL. More interestingly, the five genes were positively correlated with stromal infiltration, especially in CAFs. The top two genes, FN1 and SPARC , showed a co-expression pattern, which indicates their potential as novel therapeutic targets for DLBCL., Competing Interests: Conflict-of-interest statement: All authors declare having no conflict of interests., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

We report the discovery of an extended very-high-energy (VHE) gamma-ray source around the location of the middle-aged (207.8 kyr) pulsar PSR J0622+3749 with the Large High-Altitude Air Shower Observatory (LHAASO). The source is detected with a significance of 8.2σ for E>25  TeV assuming a Gaussian template. The best-fit location is (right ascension, declination) =(95.47°±0.11°,37.92°±0.09°), and the extension is 0.40°±0.07°. The energy spectrum can be described by a power-law spectrum with an index of -2.92±0.17&#95;{stat}±0.02&#95;{sys}. No clear extended multiwavelength counterpart of the LHAASO source has been found from the radio to sub-TeV bands. The LHAASO observations are consistent with the scenario that VHE electrons escaped from the pulsar, diffused in the interstellar medium, and scattered the interstellar radiation field. If interpreted as the pulsar halo scenario, the diffusion coefficient, inferred for electrons with median energies of ∼160  TeV, is consistent with those obtained from the extended halos around Geminga and Monogem and much smaller than that derived from cosmic ray secondaries. The LHAASO discovery of this source thus likely enriches the class of so-called pulsar halos and confirms that high-energy particles generally diffuse very slowly in the disturbed medium around pulsars.

The extension of the cosmic-ray spectrum beyond 1 petaelectronvolt (PeV; 10 15 electronvolts) indicates the existence of the so-called PeVatrons-cosmic-ray factories that accelerate particles to PeV energies. We need to locate and identify such objects to find the origin of Galactic cosmic rays 1 . The principal signature of both electron and proton PeVatrons is ultrahigh-energy (exceeding 100 TeV) γ radiation. Evidence of the presence of a proton PeVatron has been found in the Galactic Centre, according to the detection of a hard-spectrum radiation extending to 0.04 PeV (ref. 2 ). Although γ-rays with energies slightly higher than 0.1 PeV have been reported from a few objects in the Galactic plane 3-6 , unbiased identification and in-depth exploration of PeVatrons requires detection of γ-rays with energies well above 0.1 PeV. Here we report the detection of more than 530 photons at energies above 100 teraelectronvolts and up to 1.4 PeV from 12 ultrahigh-energy γ-ray sources with a statistical significance greater than seven standard deviations. Despite having several potential counterparts in their proximity, including pulsar wind nebulae, supernova remnants and star-forming regions, the PeVatrons responsible for the ultrahigh-energy γ-rays have not yet been firmly localized and identified (except for the Crab Nebula), leaving open the origin of these extreme accelerators.

Recurrent pregnancy loss (RPL) is a disturbing disease in women, and 50% of RPL is reported to be associated with immune dysfunction. Most previous studies of RPL focused mainly on the relationship between RPL and either T cells or natural killer (NK) cells in peripheral blood and the decidua; few studies presented the systemic profiles of the peripheral immune cell subsets in RPL women. Herein, we simultaneously detected 63 immune cell phenotypes in the peripheral blood from nonpregnant women (NPW), women with a history of normal pregnancy (NP) and women with a history of RPL (RPL) by multi-parameter flow cytometry. The results demonstrated that the percentages of naïve CD4 + T cells, central memory CD4 + T cells, naïve CD8 + T cells, mature NK cells, Vδ1 + T cells and the ratio of Vδ1 + T cells/Vδ2 + T cells were significantly higher in the RPL group than those in the NPW and NP groups, whereas the percentages of terminal differentiated CD4 + T cells, effective memory CD4 + T cells, immature NK cells and Vδ2 + T cells were significantly lower in the RPL group than those in the NPW and NP groups. Interestingly, we found that peripheral T helper (T PH ) cells were more abundant in the NPW group than in the NP and RPL groups. In addition, we also determined the 5 th percentile lower limit and 95 th percentile upper limit of the significantly changed immunological parameters based on the files of the NPW group. Taken together, this is the first study to simultaneously characterize the multiple immune cell subsets in the peripheral blood at a relatively large scale in RPL, which might provide a global readout of the immune status for clinicians to identify clinically-relevant immune disorders and guide them to make clear and individualized advice and treatment plans., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liu, Lin, Huang, Huang, Song, Chen, Tang, Tao, Yin, Mor and Liao.)

The combination of transition-metal catalysis and organocatalysis increasingly offers chemists opportunities to realize diverse unprecedented chemical transformations. By combining iridium with chiral thiourea catalysis, direct enantioselective reductive cyanation and phosphonylation of secondary amides have been accomplished for the first time for the synthesis of enantioenriched chiral α-aminonitriles and α-aminophosphonates. The protocol is highly efficient and enantioselective, providing a novel route to the synthesis of optically active α-functionalized amines from the simple, readily available feedstocks. In addition, the reactions are scalable and the thiourea catalyst can be recycled and reused., (© 2021 Wiley-VCH GmbH.)

Background: In the context of increasing doctor-patient tensions in China, the objective of this study was to explore and examine the effects of loving-kindness meditation (LKM) on doctors' mindfulness, empathy, and communication skills., Methods: A total of 106 doctors were recruited from a hospital in China, and randomly divided into an LKM training group (n = 53) and waiting control group (n = 53). The LKM training group received 8 weeks of LKM training intervention, whereas the control group received no intervention. Three major variables (mindfulness, empathy, and communication skills) were measured before (pre-test) and after (post-test) the LKM training intervention., Results: The empathy and communication skills of the LKM group were significantly improved compared with those of the control group, but the level of mindfulness did not significantly change., Conclusions: The results suggested that LKM may contribute to improving physicians' empathy and communication skills. However, the mechanisms that underlie the effects of the LKM on mindfulness, empathy, and communication skills and other psychological constructs needs further elucidation.

A new flavonoid named saniculamin C ( 1 ), together with six known compounds ( 2-7 ), were isolated from the whole plants of Sanicula lamelligera Hance. The chemical structures were elucidated by spectroscopic and physico-chemical analyses. All isolates were evaluated for in vitro cytotoxic activities against four human cancer cell lines, HepG2, SGC-7901 gastric cancer, Hela and A-549 lung cancer. Compound 1 showed potent antiproliferative activities against SGC-7901 cells with IC 50 value of 7.45 μM. In addition, compound 6 exhibited weak antiproliferative activities against HepG2, SGC-7901, Hela cancer cells with IC 50 values of 10.43, 8.24 and 15.32 μM, respectively.[Formula: see text].

Twelve undescribed lanostane-type triterpenes, and twenty-two known triterpenes were isolated and identified from a medicinal bracket fungus Fomitopsis pinicola (Sw.) P. Karst. The structures of these compounds were determined by spectroscopic and spectrometric analyses. The antiinflammatory potential of thirty-two triterpene compounds was evaluated using neutrophils as an assay model, and pinicolasin J was the most potent inhibitor of superoxide anion generation and elastase release, with IC 50 values of 1.81 ± 0.44 and 2.50 ± 0.64 μM, respectively. This study provides scientific insight into the nutritional supplement value and medicinal development of Fomitopsis pinicola., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The complexity of healthcare and concurrent advances in technology have promoted Interprofessional Education (IPE) in healthcare schools to prepare students to collaborate on interdisciplinary teams. Since 2016, healthcare curricula in Taiwan have incorporated IPE-based capstone courses to enhance creativity. To better understand the predictors of team creativity could help educators improve IPE and outcomes for nursing students and patients., Purpose: To determine whether nursing students' demographic characteristics, individual creativity, and perceived team interaction behaviors, team swift trust, team conflict, and team task interdependence may predict high perceived team creativity in IPE settings., Methods: A cross-sectional study design included nursing students (N = 99) at a science and technology university in Taiwan. Data from self-report questionnaires included variables for demographic characteristics, individual creativity, and perceived team characteristics. A hierarchical multiple regression analysis revealed predictors of high perceived team creativity., Results: Nursing students who perceived high team creativity also perceived higher interaction behaviors and lower process conflict than those who perceived less creativity. Spontaneous communication and team task conflict predicted high perceived team creativity., Conclusions: Nursing educators could increase team creativity in IPE by encouraging spontaneous communication and constructive task-oriented conflict management. This may benefit patient outcomes in the future., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The literature emphasizes the importance of matching the demand and supply of endocrinology and metabolism (EM) specialists. This study analyzed the current status of EM specialists in Taiwan. The gender effects on the workplace of EM specialists were also evaluated., Methods: The number of internal medicine (IM) specialists was obtained from the websites of the Ministry of Health and Welfare. Data about EM specialists were retrieved from the database of the Endocrine Society of the Republic of China (ESROC; Taiwan). Differences in age distribution and workplace levels or locations between female and male EM specialists were analyzed., Results: Since 1988, 809 physicians were certified as EM specialists. The average age of 739 EM specialists (509 male, 230 female) who remained as active members of the ESROC was 49.9 ± 11.1 years. The age distribution (p < 0.001) and workplace location (p = 0.043) were significantly different between male and female EM specialists. Divided by decades, the ratio of female-to-male EM specialists revealed an increasing tendency (p < 0.001). The percentage of EM specialists among IM specialists, certified 2 years previously, declined from 14.0% in 2017 to 7.9% and 8.3% in 2018 and 2019, respectively., Conclusion: The female-to-male ratio of EM specialists increased gradually. Compared to males, female EM specialists were relatively younger, and more of them had clinical practice in northern Taiwan. The percentage of IM specialists becoming EM specialists declined in the last 2 years. The equilibrium between the supply and demand of EM specialists deserves further investigation., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest relevant to this article., (Copyright © 2020 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

This study investigates the application of the paramagnetic shift reagent tris(dipivaloylmethanato)-europium(III) in NMR spectral studies of permethoxyacridone alkaloids ( 1 - 3 ) and pyranoacridone alkaloids ( 4 - 6 ). The induced chemical shifts (∆δ) of all protons were observed for the same molecule, and were compared to deduce the positions resulting from the distance nearby the Eu(dpm) 3 . Assignment of the H-2, H-4 and H-8 of polysubstituted acridones could be distinguished based on the least-squares method of lanthanide-induced shifts plotted against the mole ratios of Eu(dpm) 3 to the substrate. The developed method is not only potentially useful for determining the planar structures of polysubstituted compounds, such as acridones, anthraquinones, xanthones, flavonoids, and phenanthrenes, but also applicable for their stereochemistry.

Caused by a novel type of virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), coronavirus disease 2019 (COVID-19) constitutes a global public health emergency. Pregnant women are considered to have a higher risk of severe morbidity and even mortality due to their susceptibility to respiratory pathogens and their particular immunologic state. Several studies assessing SARS-CoV-2 infection during pregnancy reported adverse pregnancy outcomes in patients with severe conditions, including spontaneous abortion, preterm labor, fetal distress, cesarean section, preterm birth, neonatal asphyxia, neonatal pneumonia, stillbirth, and neonatal death. However, whether these complications are causally related to SARS-CoV-2 infection is not clear. Here, we reviewed the scientific evidence supporting the contributing role of Treg/Th17 cell imbalance in the uncontrolled systemic inflammation characterizing severe cases of COVID-19. Based on the recognized harmful effects of these CD4 + T-cell subset imbalances in pregnancy, we speculated that SARS-CoV-2 infection might lead to adverse pregnancy outcomes through the deregulation of otherwise tightly regulated Treg/Th17 ratios, and to subsequent uncontrolled systemic inflammation. Moreover, we discuss the possibility of vertical transmission of COVID-19 from infected mothers to their infants, which could also explain adverse perinatal outcomes. Rigorous monitoring of pregnancies and appropriate measures should be taken to prevent and treat early eventual maternal and perinatal complications., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Recently, empirical researchers have observed direct associations between conflict and interaction behaviors within organizational teams. However, research concerning indirect links between conflict and interaction behaviors on interdisciplinary teams in nursing school is scant, particularly in Taiwan., Objectives: The aim of this study was to explore the relationships among various types of conflict and interaction behaviors on interdisciplinary nursing education teams., Design, Setting, and Participants: This study utilized a cross-sectional, quantitative, descriptive design. The authors collected survey data from 99 nursing students who participated in 18-week capstone courses of small interdisciplinary groups collaborating to design healthcare products in Taiwan during 2018 and 2019., Methods: Questionnaires assessed the nursing students' perceptions about their teams' conflicts (of task, process, and relationship), and interaction behaviors (constructive controversy, helping behaviors, and spontaneous communication). The authors used descriptive statistics to compare demographics, conflict scores, and interaction behavior scores for collocated and distributed interdisciplinary teams. A Pearson's analysis identified correlations among the variables and their components, and the SPSS PROCESS macro showed moderating effects of spontaneous communication on the relationship between distributed team and conflict subscales., Results: After confirming the distributed team experienced significantly more conflict than the collocated team, we found significant negative correlations between constructive controversy and both process conflict and relationship conflict on the distributed team. Another interaction behavior, spontaneous communication, had a moderating effect on the relationships between the distributed team and both task conflict and relationship conflict., Conclusion: In interdisciplinary educational settings for nursing students, spontaneous communication may moderate the types of conflict that distributed teams are more likely than collocated teams to experience. Constructive controversy may be especially effective at mitigating conflict on distributed teams. Nursing educators may refer to these insights to improve outcomes for educational interdisciplinary healthcare teams., Competing Interests: Declaration of competing interest No competing interests are declared by the authors., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Vancomycin remains a mainstay of the treatment of Gram-positive bacterial infections. It is crucial to accurately determine vancomycin serum concentration for adequate dose adjustment., Objectives: To evaluate the precision and accuracy of commercial assay techniques for vancomycin concentration and to assess the comparability of vancomycin detection methods in Chinese laboratories., Methods: Human serum samples spiked with known concentrations of vancomycin were provided to laboratories participating in the external quality assessment scheme (EQAS). Assay methods included chemiluminescence, enzyme immunoassay (EIA) and so on. The dispersion of the measurements was analysed and the robust coefficient of variation (rCV), relative percentage difference (RPD) and satisfactory rate for method groups were calculated. Moreover, performance of the Chinese laboratories was assessed., Results: A total of 657 results from 75 laboratories were collected, including 84 samples from 10 Chinese laboratories. The median rCV, median RPD and satisfactory rates classified by methods ranged from 1.85% to 15.87%, -14.75% to 13.34% and 94.59% to 100.00%, respectively. Significant differences were seen in precision, between kinetic interaction of microparticles in solution (KIMS) and other methods, and in accuracy, between enzyme-multiplied immunoassay technique (EMIT), fluorescence polarization immunoassay (FPIA) and other techniques. Vancomycin detection in China mainly depended on the chemiluminescence and EMIT methods, which tended to result in lower measurements., Conclusions: Although almost all assays in this study achieved an acceptable performance for vancomycin serum concentration monitoring, obvious inconsistencies between methods were still observed. Chinese laboratories were more likely to underestimate vancomycin concentrations. Thus, recognizing inconsistencies between methods and regular participation in vancomycin EQAS are essential., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Four new sesquiterpenes (1-4), one new alkaloid (5), and one new benzenoid glycoside (6) were characterized from Lindera aggregata, and their structures were elucidated according to their spectrometric analytical data. Among these isolates, 3 and 4 were constructed as possessing unprecedented carbon skeletons from the natural source. Some of these purified constituents were examined for their anti-inflammatory bioactivity. Among the tested compounds, linderaggredin C (3), (+)-N-methyllaurotetanine, and (+)-isoboldine displayed the significant inhibition of superoxide anion generation in human neutrophils with IC 50 values of 7.45 ± 0.74, 8.36 ± 0.11, and 5.81 ± 0.59 μM, respectively., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Induction of the inflammasome protein cryopyrin (NLRP3) in visceral adipose tissue (VAT) promotes release of the proinflammatory cytokine IL-1β in obesity. Although this mechanism contributes to peripheral metabolic dysfunction, effects on the brain remain unexplored. We investigated whether visceral adipose NLRP3 impairs cognition by activating microglial IL-1 receptor 1 (IL-1R1). After observing protection against obesity-induced neuroinflammation and cognitive impairment in NLRP3-KO mice, we transplanted VAT from obese WT or NLRP3-KO donors into lean recipient mice. Transplantation of VAT from a WT donor (TRANSWT) increased hippocampal IL-1β and impaired cognition, but VAT transplants from comparably obese NLRP3-KO donors (TRANSKO) had no effect. Visceral adipose NLRP3 was required for deficits in long-term potentiation (LTP) in transplant recipients, and LTP impairment in TRANSWT mice was IL-1 dependent. Flow cytometric and gene expression analyses revealed that VAT transplantation recapitulated the effects of obesity on microglial activation and IL-1β gene expression, and visualization of hippocampal microglia revealed similar effects in vivo. Inducible ablation of IL-1R1 in CX3CR1-expressing cells eliminated cognitive impairment in mice with dietary obesity and in transplant recipients and restored immunoquiescence in hippocampal microglia. These results indicate that visceral adipose NLRP3 impairs memory via IL-1-mediated microglial activation and suggest that NLRP3/IL-1β signaling may underlie correlations between visceral adiposity and cognitive impairment in humans.

Molecular dynamics simulations of Ni36Zr64, Cu65Zr35 and Ni80Al20 were carried out over a broad range of temperature (900-3000 K) to investigate the Stokes-Einstein (SE) relation for glass-forming melts. Our results reproduce experimental structural and transport properties. Results show that the breakdown temperature of the SE relation (TSE) equals the dynamical crossover temperature (TA) and both are roughly twice the glass-transition temperature (Tg) for the three glass-forming melts (TSE = TA ≈ 2.0Tg). The product of the individual component self-diffusion coefficient and viscosity Dαη can be roughly regarded as a constant at the transition zone (a small temperature range around TSE) in which the temperature behaviors of self-diffusion coefficient and viscosity switch from high-temperature Arrhenius to a low-temperature VFT behavior. Below TSE, the decoupling of component diffusion coefficients was found. In particular, the decoupling of component diffusion coefficients can be ascribed to the decoupling of the partial pair structural correlation of components, which can be clearly reflected by the intersection of the high-temperature and low-temperature behaviors of the ratio between the partial pair correlation entropy of components (Sβ2/Sα2). Furthermore, the ratio between the partial pair correlation entropy of components may be used to predict the validity of the SE relation, in the absence of both transport coefficients and atomic coordinates.

Objectives: The prevalence of diabetes mellitus has recently increased in Taiwan, and depression is common among these patients. Moreover, a lack of health literacy may lead to depression. In this study, we explored the correlation between health literacy and depression in diabetic women., Methods: In this cross-sectional study, 152 women with type 2 diabetes mellitus were recruited from the outpatient clinic of a regional teaching hospital in Taiwan. The data were collected through medical records and a self-reported structured questionnaire, which included items on basic attributes, self-rated health status, the Center for Epidemiologic Studies Depression Scale (CES-D), and Chinese Health Literacy Scale for Diabetes (CHLSD). The results were analyzed using descriptive statistical analyses, bivariate correlation tests, and linear regression analyses., Results: One hundred thirty-five valid questionnaires were obtained. Approximately 20% of the participants had a higher tendency toward depression as per their CES-D score, and the CHLSD results showed that 13.33% had poor health literacy. There was a negative correlation between health literacy and depressive tendencies after adjusting for self-rated health status, economic satisfaction status, employment status, and education level using multivariate linear regression analyses. For each 1-point rise in the CHLSD score, the CES-D score decreased by 0.17 points (z=-2.05, p=0.042)., Conclusions: A negative correlation was identified between health literacy and depression. Self-rated health status, economic satisfaction, employment status, and higher education level are factors that also affect depressive tendency among diabetic women.

Efficient conversion of renewable biomass platform chemicals into high-quality fuels remains challenging. A one-pot catalytic approach has been developed to synthesize various structurally defined biofuels by using Hf(OTf) 4 and Pd/C for selective tandem catalysis and 2-methylfuran (2-MF) as a renewable feedstock. 2-MF first undergoes Lewis acid-catalyzed hydroxyalkylation/alkylation (HAA) condensation with carbonyl compounds to afford intermediates containing the targeted carbon skeletons of hydrocarbon or ether products, and these intermediates then undergo hydrogenation or hydrodeoxygenation to afford the target products, catalyzed by metal triflate+Pd/C in the same pot. The present process can produce structurally defined alkanes and cyclic ethers under mild conditions., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Hepatocellular carcinoma (HCC) is one of the primary causes of cancer‑associated deaths worldwide. Current treatment methods include surgical resection, chemotherapy and radiotherapy; however the curative rate remains low, thus novel treatments are required. The aim of the present study was to investigate the role of targeting protein for Xenopus kinesin‑like protein 2 (TPX2) in the growth of HCC and its underlying molecular mechanism. Immunohistochemistry staining, reverse transcription‑quantitative (RT‑q)PCR and western blotting were used to detect the expression of TPX2 mRNA and protein in liver cancer tissue samples, adjacent normal liver tissue samples, and the HCC cell lines Huh7, Hep3B, PLC/PRF/5 and MHCC97‑H. The recombinant plasmid pMagic4.1‑shRNA‑TPX2 was constructed and transfected into Huh7 and Hep3B HCC cells to silence TPX2 expression. The proliferation, apoptosis, migration and invasion of Huh7 cells and Hep3B cells were evaluated before and after TPX2 silencing. The mRNA and protein expression levels of multiple signaling pathway‑associated genes were detected by RT‑qPCR and western blotting. The expression levels of TPX2 mRNA and protein were significantly higher in HCC tissue samples compared with adjacent normal liver tissue sample. TPX2 mRNA and protein expression levels were detected in the different HCC cell lines. The recombinant plasmid pMagic4.1‑shRNA‑TPX2 was successfully transfected into Huh7 and Hep3B cells, resulting in TPX2 silencing. TPX2 knockdown significantly reduced cell proliferation, cell migration and cell invasion of Huh7 and Hep3B cells, whilst also increasing the rate of apoptosis in these cells. Following TPX2 silencing, the expression levels of PI3K, phospho‑AKT, Bcl‑2, c‑Myc and Cyclin D1 were significantly decreased, whereas the expression levels of P21 and P27 were significantly increased. In conclusion, TPX2 may suppress the growth of HCC by regulating the PI3K/AKT signaling pathway and thus, TPX2 may be a potential target for the treatment of liver cancer.

Many health care education programs, particularly those in Taiwan, have begun offering capstone product-based curricula, not only to improve nursing students' problem-solving skills but also to foster creativity and innovation regarding health care issues. This study used a cross-sectional quantitative design to explore the efficacy of teaching for creativity among nurse faculty in Taiwan. Results showed knowledge of intellectual property rights was low, as was ability to creatively evaluate trademark and patent designs. Curiosity was the main predictor associated with self-efficacy of teaching for creativity.

Twelve undescribed sesquiterpenoids, fomitopins A-L (1-12), were isolated via bioassay-guided purification from the bracket fungus Fomitopsis pinicola (Sw.) P. Karst, and this fungus have been reported to exhibit anti-microbial and anti-inflammatory activities. The structures of 1-12 were elucidated by spectroscopic and spectrometric analyses and their absolute configurations were further confirmed by ECD simulations. Ten isolated compounds were evaluated for their anti-inflammatory potential and compound 11 exhibited the most significant inhibition of superoxide anion generation and elastase release with IC 50 values of 0.81 ± 0.15 and 0.74 ± 0.12 μM. These newly purified sesquiterpenoids could be potential candidates for further anti-inflammatory studies., Competing Interests: The authors declare no competing financial interest., (This journal is © The Royal Society of Chemistry.)

Objective: To investigate the expression of Golgi phosphoprotein 3 (GOLPH3) in papillary thyroid carcinoma (PTC) and its relationship with clinicopathological characteristics of PTC and American Thyroid Association (ATA) risk of recurrence stratification. Methods: The mRNA expression level of GOLPH3 in PTC tissues and the matched adjacent noncancerous tissues from 30 cases of PTC undergoing surgical operation in Fujian Provincial Hospital between March 2017 and April 2018 was detected by reverse transcription-quantitative PCR (RT-qPCR). The protein expression of GOLPH3 in PTC tissues and the matched adjacent noncancerous tissues of 135 cases of PTC between January 2013 and April 2018 was measured by immunohistochemistry. The correlation between the expression of GOLPH3 in PTC and clinicopathologic characteristics and ATA risk of recurrence stratification was analyzed. Results: The mRNA level of GOLPH3 in PTC tissues was significantly higher than that in adjacent noncancerous tissues (7.53±1.32 vs 3.64±1.44, P< 0.001). The protein expression level of GOLPH3 in PTC tissues was significantly higher than that in adjacent noncancerous tissues [66(30, 95) vs 34(20, 72), P< 0.001]. The expression of GOLPH3 was significantly correlated to the tumor size ( P= 0.026), extrathyroid invasion ( P= 0.016), lymph node metastasis ( P= 0.001) and TNM stage ( P= 0.027) in PTC. Multivariate logistic regression analysis showed that GOLPH3 expression was independently correlated to tumor size ( OR= 3.58, 95 %CI : 1.19-15.46, P= 0.017) and lymph node metastasis ( OR= 7.28, 95 %CI : 2.43-10.08, P= 0.002). The expression of GOLPH3 was positively correlated to ATA risk of recurrence stratification ( P= 0.041). Conclusions: Overexpression of GOLPH3 is associated with the development of PTC and poor prognosis in patients with PTC. Detection of GOLPH3 expression can help evaluate proliferative and metastatic potential of PTC, as well as the risk of postoperative recurrence in patients with PTC.

Research Question: How can the kinetics of human blastocyst expansion be used to evaluate an embryo's ploidy identified using preimplantation genetic testing for aneuploidy (PGT-A)?, Design: This was a retrospective observational study of 188 autologous blastocysts from 34 sequential treatment cycles using PGT-A and blastocyst biopsy. Using time-lapse imaging, blastocyst expansion was evaluated using a quantitative standardized expansion assay (qSEA). Trophectoderm cell division was examined in selected, unbiopsied embryos (n = 7) to evaluate the contribution of mitosis to the expansion rate., Results: The averaged euploid blastocyst expansion rate was significantly (52.8%) faster than in aneuploid blastocysts (P = 0.0041). Scatterplots, representing 'expansion maps', revealed that both populations showed a similarly overlapping distribution of blastocyst formation times at 80-140 h from fertilization. Euploidy and aneuploidy were better distinguished in regions of higher and lower expansion, respectively, in expansion maps. Based upon the expansion slopes, rank-ordering of individual embryos within cohorts resulted in more than 90% euploid embryos in the first two ranks in patients less than 35 years of age. Additional detailed time-lapse image analysis provided evidence that rapid expansion was associated with robust, integrative cellular mitosis in trophectoderm cells., Conclusions: The kinetics of human blastocyst expansion are related to an embryo's ploidy. These preliminary observations describe a new quantitative, non-invasive approach to embryo assessment that may be useful to identify single blastocysts for transfer, particularly in younger patient groups. However, this approach may also be useful for euploid embryo selection after PGT-A. The results support the hypothesis that aneuploidy universally impairs general cellular processes, including cell division, in differentiated cells., (Copyright © 2019. Published by Elsevier Ltd.)

Purposes: We investigated the influences of prognostic factors on long-term survival of patients with follicular thyroid cancer (FTC) based on all-cause mortality and two exclusive causes of death, FTC and non-FTC., Methods: In this retrospective cohort study, we collected data of 204 patients with FTC diagnosed between 1985 and 2007 at National Taiwan University Hospital. For all-cause mortality, Cox proportional hazards models were used to estimate hazard ratios for prognostic factors. Cause-specific hazard and cumulative incidence function models were used to determine the influences of prognostic factors on FTC and non-FTC death, respectively. The dynamic processes of distant metastases and locoregional recurrences were included as time-varying factors in all models., Results: The cumulative incidence of all-cause death was 24% and 45% at 10 and 20-years, respectively. Multivariate analyses identified that distant metastases, locoregional recurrences, and positive surgical margins were significant independent risk factors for overall survival, hazard, and cumulative incidence of FTC death. Age at diagnosis >60 years increased the risks of all-cause and non-FTC death as well as cumulative incidence of non-FTC death. Tumor size >4 cm had a harmful effect on overall survival. Female patients had higher risk and cumulative incidence of FTC death, but male patients had a higher cumulative incidence of non-FTC death. Lymph node metastases significantly increased the cumulative incidence of FTC death., Conclusion: Dynamic distant metastases and locoregional recurrences were the most dominant risk factors influencing FTC-specific hazard and cumulative incidence for FTC death by accounting for non-FTC death as a competing risk for FTC patients., (Copyright © 2018 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Obesity and insulin resistance elicit blood-brain barrier (BBB) breakdown in humans and animal models, but the relative contributions of the two pathologies remain poorly understood. These studies initially addressed the temporal progression of cerebrovascular dysfunction relative to dietary obesity or diet-induced insulin resistance in male mice. Obesity increased BBB permeability to the low molecular weight fluorophore sodium fluorescein (NaFl), whereas diet-induced insulin resistance increased permeability to both NaFl and Evans blue, which forms a high molecular weight complex with serum albumin. Serial section transmission electron microscopy analysis of hippocampal capillaries revealed that diabetes promotes involution of tight junctions, fenestration of endothelial cells, and pericyte regression. Chronic activation of adenosine receptor 2a (Adora2a) erodes tight junctions between endothelial cells of the cerebral vasculature in other models of chronic neuropathology, and we observed that acute Adora2a antagonism normalized BBB permeability in wild-type mice with diet-induced insulin resistance. Experiments in mice with inducible deletion of Adora2a in endothelial cells revealed protection against BBB breakdown with diet-induced insulin resistance, despite comparable metabolic dysfunction relative to nontransgenic littermates. Protection against BBB breakdown was associated with decreased vascular inflammation, recovery of hippocampal synaptic plasticity, and restoration of hippocampus-dependent memory. These findings indicate that Adora2a-mediated signaling in vascular endothelial cells disrupts the BBB in dietary obesity, and implicate cerebrovascular dysfunction as the underlying mechanism for deficits in synaptic plasticity and cognition with obesity and insulin resistance. SIGNIFICANCE STATEMENT The blood-brain barrier (BBB) restricts the entry of circulating factors into the brain, but obesity promotes BBB breakdown in humans and animal models. We used transgenic mice with resistance to BBB breakdown to investigate the role of neurovascular dysfunction in high-fat diet (HFD)-induced cognitive impairment. Transgenic mice with inducible ablation of Adora2a in endothelial cells were protected against BBB breakdown on HFD, despite comparable metabolic impairments relative to normal mice. Transgenic mice were also resistant to HFD-induced cognitive dysfunction and were protected against deficits in hippocampal synaptic plasticity. These findings indicate that Adora2a-mediated signaling in endothelial cells mediates obesity-induced BBB breakdown, and implicate cerebrovascular dysfunction as the mechanism for deficits in synaptic plasticity and cognition with obesity and diabetes., (Copyright © 2019 the authors.)