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Abstract Two important factors affecting the progress of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are the S-protein binding function of ACE2 receptors and the membrane fluidity of host cells. This study aimed to evaluate the effect of static magnetic field (SMF) on S-protein/ACE2 binding and cellular membrane fluidity of lung cells, and was performed in vitro using a Calu-3 cell model and in vivo using an animal model. The ability of ACE2 receptors to bind to SARS-CoV-2 spike protein on host cell surfaces under SMF stimulation was evaluated using fluorescence images. Host lung cell membrane fluidity was tested using fluorescence polarization to determine the effects of SMF. Our results indicate that 0.4 T SMF can affect binding between S-protein and ACE2 receptors and increase Calu-3 cell membrane fluidity, and that SMF exposure attenuates LPS-induced alveolar wall thickening in mice. These results may be of value for developing future non-contact, non-invasive, and low side-effect treatments to reduce disease severity in COVID-19-invaded lungs.

Background: Given the established association between sarcopenia and cognitive impairment was mainly in the older and oldest-old population or people with relatively limited education, this study extends the investigation to community-dwelling middle-to-old age adults in urban communities, emphasizing the need for preventive intervention for muscle health and healthy longevity. Methods: Data of 712 participants from the Gan-Dau Healthy Longevity Plan were retrieved for analysis, and all participants were stratified by age (50–64, 65–74 and 75+ years old). Possible sarcopenia was defined by 2019 consensus report of the Asian Working Group for Sarcopenia (AWGS). This study used four neuropsychological tests for analysis, i.e., Mini-Mental Status Examination (MMSE), California Verbal Learning Test II (CVLT-SF), Digital Symbol Substitution Test (DSST) and Verbal fluency (VF) for global and domain-specific cognitive function. Multivariate generalized linear models (GLMs) were employed to investigate the associations between possible sarcopenia and cognitive function in each age-specific groups. Results: The prevalence of possible sarcopenia increased with age, with 31.8 %, 37.7 %, and 55.6 % in participants aged 5064, 65–74 and, 75+ years, respectively. On the other hand, cognitive performance declined with age. In particular, among participants aged 75+ years with possible sarcopenia, their cognitive performance were poorer than robust counterparts, including MMSE (26.6 [3.4] vs. 27.4 [2.6]), CVTL-SF (total score: 21.5 [5.4] vs. 23.8 [5.5]; 30-second delayed recall: 6.0 [1.7] vs. 6.5 [1.6]), DSST (32.8 [14.3] vs. 41.3 [18.7]), and VF (12.8 [5.1] vs. 14.8 [4.9]). Multivariate generalized linear model indicated that possible sarcopenia was associated with lower MMSE (β: −0.70, p = 0.014) and lower DSST (β: −7.00, p = 0.010) in those aged 50–64 years. Moreover, possible sarcopenia was associated with lower CVLT-SF (total score β:-1.90, p = 0.028), lower DSST (β: −6.45, p

Abstract Colorectal cancer (CRC) patients who receive cancer surgeries from higher-volume providers may have better outcomes. However, the definitions of surgical volume may affect the results. We aim to analyze the effects of different definitions of surgical volume on patient outcomes. We conducted a nationwide population-based study in Taiwan that enrolled all patients who underwent definitive surgery for newly diagnosed CRC. We used three common definitions of surgical volume: total volume means the total surgical number conducted by the same provider during the study period; cumulative volume was calculated as the number of operations the surgeon performed before the index procedure; annual volume was calculated as the number of times the surgeon had been responsible for surgery during the index year. In this study, we included 100,009 newly diagnosed CRC patients, including 55.8% males, of median age 66 years at diagnosis (range 20–105 years). After adjustment for the patient and provider characteristics, we found that CRC patients receiving definitive surgery by higher-volume providers had better outcomes, especially where surgeon volume may play a more important role than hospital volume. The cumulative volume could predict the 5-year mortality of the study cohort better than the total and annual volume.

Purpose: Obstructive sleep apnea (OSA) is a chronic disease that affects 1%–6% of children. Our study aims to explore the effectiveness and clinical characteristics of integrative Traditional Chinese Medicine (ITCM) for pediatric OSA. Materials and methods: In this retrospective cohort study, we assessed differences of polysomnography (PSG) parameters and clinical characteristics between 2009 and 2020. Children

In 2019, the coronavirus pandemic was caused by severe acute respiratory syndrome coronavirus 2. In Taiwan, an inflatable negative pressure isolation chamber (INPIC) was applied into the emergency air medical transport (EAMT) in 2020. The standard operating procedure of the INPIC as infection control was developed and practiced in the UH-60M helicopter. There were five cases moved by the EAMT from the Lanyu Township and Ludao Township to Taiwan's mainland. After they were screened positive for coronavirus disease 2019 (COVID-19) with a rapid test, the medical staff completed the INPIC preparation and loaded the patients into it before the EAMT. This study reported that none of the crewmembers were infected with COVID-19 during the transfers. However, some restrictions of the INPIC could be improved in the future, e.g. limited space, thermal stress, equipment immobilization, and communication barrier. The medical team should assess the efficiency and safety using the INPIC based on each patient's condition before the flight.

Abstract Background Protein phosphatase 2A (PP2A) is one of the major protein phosphatases in eukaryotic cells and is essential for cellular homeostasis. PP2A is a heterotrimer comprising the dimeric AC core enzyme and a highly variable regulatory B subunit. Distinct B subunits help the core enzyme gain full activity toward specific substrates and contribute to diverse cellular roles of PP2A. PP2A has been thought to play a tumor suppressor and the B56γ3 regulatory subunit was shown to play a key tumor suppressor regulatory subunit of PP2A. Nevertheless, we uncovered a molecular mechanism of how B56γ3 may act as an oncogene in colorectal cancer (CRC). Methods Polyclonal pools of CRC cells with stable B56γ3 overexpression or knockdown were generated by retroviral or lentiviral infection and subsequent drug selection. Co-immunoprecipitation(co-IP) and in vitro pull-down analysis were applied to analyze the protein–protein interaction. Transwell migration and invasion assays were applied to investigate the role of B56γ3 in affecting motility and invasive capability of CRC cells. The sensitivity of CRC cells to 5-fluorouracil (5-FU) was analyzed using the PrestoBlue reagent assay for cell viability. Immunohistochemistry (IHC) was applied to investigate the expression levels of phospho-AKT and B56γ3 in paired tumor and normal tissue specimens of CRC. DataSets of TCGA and GEO were analyzed to investigate the correlation of B56γ3 expression with overall survival rates of CRC patients. Results We showed that B56γ3 promoted epithelial-mesenchymal transition (EMT) and reduced the sensitivity of CRC cells to 5-FU through upregulating AKT activity. Mechanistically, B56γ3 upregulates AKT activity by targeting PP2A to attenuate the p70S6K-mediated negative feedback loop regulation on PI3K/AKT activation. B56γ3 was highly expressed and positively correlated with the level of phospho-AKT in tumor tissues of CRC. Moreover, high B56γ3 expression is associated with poor prognosis of a subset of patients with CRC. Conclusions Our finding reveals that the B56γ3 regulatory subunit-containing PP2A plays an oncogenic role in CRC cells by sustaining AKT activation through suppressing p70S6K activity and suggests that the interaction between B56γ3 and p70S6K may serve as a therapeutic target for CRC. Video Abstract

PurposeThe purposes of this study were to determine whether biomechanical properties of mature oocytes could predict usable blastocyst formation better than morphological information or maternal factors, and to demonstrate the safety of the aspiration measurement procedure used to determine the biomechanical properties of oocytes.MethodsA prospective split cohort study was conducted with patients from two IVF clinics who underwent in vitro fertilization. Each patient's oocytes were randomly divided into a measurement group and a control group. The aspiration depth into a micropipette was measured, and the biomechanical properties were derived. Oocyte fertilization, day 3 morphology, and blastocyst development were observed and compared between measured and unmeasured cohorts. A predictive classifier was trained to predict usable blastocyst formation and compared to the predictions of four experienced embryologists.Results68 patients and their corresponding 1252 oocytes were included in the study. In the safety analyses, there was no significant difference between the cohorts for fertilization, while the day 3 and 5 embryo development were not negatively affected. Four embryologists predicted usable blastocyst development based on oocyte morphology with an average accuracy of 44% while the predictive classifier achieved an accuracy of 71%. Retaining the variables necessary for normal fertilization, only data from successfully fertilized oocytes were used, resulting in a classifier an accuracy of 81%.ConclusionsTo date, there is no standard guideline or technique to aid in the selection of oocytes that have a higher likelihood of developing into usable blastocysts, which are chosen for transfer or vitrification. This study provides a comprehensive workflow of extracting biomechanical properties and building a predictive classifier using these properties to predict mature oocytes' developmental potential. The classifier has greater accuracy in predicting the formation of usable blastocysts than the predictions provided by morphological information or maternal factors. The measurement procedure did not negatively affect embryo culture outcomes. While further analysis is necessary, this study shows the potential of using biomechanical properties of oocytes to predict embryo developmental outcomes.

Abstract Smoking rates in the military are evaluated through questionnaire surveying. Because the accurate identification of smokers facilitates the provision of smoking cessation services, this study conducted urine cotinine concentration testing to verify the accuracy of self-reported smoking behavior by female volunteer soldiers and analyzed the effects of second-hand smoking on urine cotinine concentrations. This study is a cross-sectional study conducted using purposive sampling on female volunteer soldiers receiving training at the Taichung Recruit Training Center in May 2014. This study simultaneously collected questionnaires and urine samples, and urine samples were analyzed with an enzyme-linked immunosorbent assay. The self-reported smoking rate of female volunteer soldiers was 19.3%, whereas the smoking rate as determined by urine cotinine concentration testing was 26.3%, indicating an overall underestimation of 7.0%. Chi-square (χ2) goodness of fit test results indicated that the distribution of self-reported smoking behaviors and that verified from urine cotinine concentration testing were significantly different. The sensitivity of self-reported smoking behavior was 66.7% with a specificity of 97.6%. There was no significant association between second-hand smoking and urine cotinine concentrations. Questionnaire survey self-reporting methods could underestimate the smoking behavior of female volunteer soldiers and routine testing with biochemical verification is necessary.

Abstract In cell culture environment, some cells adhere firmly to the culture plates and may be vulnerable to cell detachment during passage. Therefore, it is important to harvest cells with a proper detaching method to maintain the viability of cells after detachment. Trypsinization is frequently used for cellular dissociation and detachment. However, most surface proteins and the extracellular matrix are degraded by enzymatic digestion. A mild cell detachment buffer, accutase, is recommended for the replacement of trypsin to dissociate adherent cells and thereby avoid cellular damage. In this study, we demonstrated that use of accutase for cellular detachment may compromise some surface proteins. Compared with ethylenediaminetetraacetic acid (EDTA)-based nonenzymatic cell dissociation buffers, accutase was associated with significant decreases in the surface Fas ligands and Fas receptors. Moreover, we found that accutase may be able to cleave surface Fas ligands into pieces. Our results also illustrated that surface proteins required 20 h to recover after accutase treatment. We demonstrated that using accutase to dissociate adherent cells compromised the expression of Fas ligands and Fas receptors on the cell surface. These findings indicate that it is important to choose suitable cell detachment buffers and allow cells to recover after detachment before experiments.

Abstract Although the function of the BRCA1 gene has been extensively studied, the relationship between BRCA1 gene expression and tumor aggressiveness remains controversial in sporadic breast cancers. Because the BRCA1 protein is known to regulate estrogen signaling, we selected microarray data of ER+ breast cancers from the GEO public repository to resolve previous conflicting findings. The BRCA1 gene expression level in highly proliferative luminal B tumors was shown to be higher than that in luminal A tumors. Survival analysis using a cure model indicated that patients of early ER+ breast cancers with high BRCA1 expression developed rapid distant metastasis. In addition, the proliferation marker genes MKI67 and PCNA, which are characteristic of aggressive tumors, were also highly expressed in patients with high BRCA1 expression. The associations among high BRCA1 expression, high proliferation marker expression, and high risk of distant metastasis emerged in independent datasets, regardless of tamoxifen treatment. Tamoxifen therapy could improve the metastasis-free fraction of high BRCA1 expression patients. Our findings link BRCA1 expression with proliferation and possibly distant metastasis via the ER signaling pathway. We propose a testable hypothesis based on these consistent results and offer an interpretation for our reported associations.

Background: In-flight spatial disorientation (SD) is a predominant threat to flight safety in aviation. This study was conducted to understand the prevalence, severity, and frequency of in-flight SD among military pilots in Taiwan. Methods: A survey was conducted to collect tri-service pilots' experiences of SD during flight. Participants completed anonymous SD questionnaires during refresher physiology training. There were 486 questionnaires delivered to trainees and the completion rate was 97.1% (n = 472). All data were processed using SPSS version 24 software (IBM, Armonk, NY, USA). Results: Of the 472 participants, the average age of the pilots was 36.7 so 7.3 years and 97.7% were male. About 80% of participants experienced in-flight SD events. There was a significant difference between prevalence of SD in fighter (87.0%), trainer (89.8%), transporter (70.6%), and helicopter (66.7%) pilots (P < 0.001). Less than 10% of the events were severe, and there was no obvious variation between aircraft types (P = 0.126). Pilots were sensitive to SD in clouds and under low visibility. Over 70% of pilots experienced visual illusions, especially loss of horizon during bad weather (45.1%), followed by leans (44.5%), false horizon (44.1%), false sense in clouds (39.6%), Coriolis illusion (25.0%), and confusion on entry to instrument meteorological conditions (25.0%). Conclusions: Our survey showed that SD is a common physiological problem among military pilots, who were easily disoriented by in-flight SD without visual cues. Visual illusion was relatively more frequent, especially for trainer and fighter pilots.

Abstract Increased heart rate (HR) is a reaction to head-to-toe gravito-inertial (G) force. The anti-G straining manoeuvre (AGSM) is the crucial technique for withstanding a high-G load. Previous studies reported the main effects of HR only or AGSM only on G tolerance. We assessed the combined effect of HR and AGSM on the outcome of 9G profile exposure. A total of 530 attempts for the 9G profile were extracted to clarify the association of interest. Subjects with an AGSM effectiveness of less than 2.5G had a 2.14-fold higher likelihood of failing in the 9G profile. Trainees with HR increases of less than 20% in the first five seconds also had higher odds of 9G profile intolerance (adjusted OR 1.83, 95% CI 1.09–3.07). The adjusted OR of 9G profile disqualification was 2.93 (95% CI 1.19–7.20) for participants with smaller HR increases and lower AGSM effectiveness. The negative effect of a smaller HR increase on the outcome was likely to be affected by improved AGSM effectiveness (adjusted OR 1.26, 95% CI 0.65–2.42). We speculate that low AGSM effectiveness and a small HR increase were separately associated with failure of high-G challenge. Nonetheless, good AGSM performance seemed to reduce the negative effect of weak HR responses on the dependent variable.

Abstract Two-dimensional (2D) ternary materials recently generated interest in optoelectronics and energy-related applications, alongside their binary counterparts. To date, only a few naturally occurring layered 2D ternary materials have been explored. The plethora of benefits owed to reduced dimensionality prompted exploration of expanding non-layered ternary chalcogenides into the 2D realm. This work presents a templating method that uses 2D transition metal dichalcogenides as initiators to be converted into the corresponding ternary chalcogenide upon addition of copper, via a solution-phase synthesis, conducted in high boiling point solvents. The process starts with preparation of VSe2 nanosheets, which are next converted into Cu3VSe4 sulvanite nanosheets (NSs) which retain the 2D geometry while presenting an X-ray diffraction pattern identical with the one for the bulk Cu3VSe4. Both the scanning electron microscopy and transmission microscopy electron microscopy show the presence of quasi-2D morphology. Recent studies of the sulfur-containing sulvanite Cu3VS4 highlight the presence of an intermediate bandgap, associated with enhanced photovoltaic (PV) performance. The Cu3VSe4 nanosheets reported herein exhibit multiple UV–Vis absorption peaks, related to the intermediate bandgaps similar to Cu3VS4 and Cu3VSe4 nanocrystals. To test the potential of Cu3VSe4 NSs as an absorber for solar photovoltaic devices, Cu3VSe4 NSs thin-films deposited on FTO were subjected to photoelectrochemical testing, showing p-type behavior and stable photocurrents of up to ~ 0.036 mA/cm2. The photocurrent shows a ninefold increase in comparison to reported performance of Cu3VSe4 nanocrystals. This proves that quasi-2D sulvanite nanosheets are amenable to thin-film deposition and could show superior PV performance in comparison to nanocrystal thin-films. The obtained electrical impedance spectroscopy signal of the Cu3VSe4 NSs-FTO based electrochemical cell fits an equivalent circuit with the circuit elements of solution resistance (Rs), charge-transfer resistance (Rct), double-layer capacitance (Cdl), and Warburg impedance (W). The estimated charge transfer resistance value of 300 Ω cm2 obtained from the Nyquist plot provides an insight into the rate of charge transfer on the electrode/electrolyte interface.

Two epigenetic pathways of transcriptional repression, DNA methylation and polycomb repressive complex 2 (PRC2), are known to regulate neuronal development and function. However, their respective contributions to brain maturation are unknown. We found that conditional loss of the de novo DNA methyltransferase Dnmt3a in mouse excitatory neurons altered expression of synapse-related genes, stunted synapse maturation, and impaired working memory and social interest. At the genomic level, loss of Dnmt3a abolished postnatal accumulation of CG and non-CG DNA methylation, leaving adult neurons with an unmethylated, fetal-like epigenomic pattern at ~222,000 genomic regions. The PRC2-associated histone modification, H3K27me3, increased at many of these sites. Our data support a dynamic interaction between two fundamental modes of epigenetic repression during postnatal maturation of excitatory neurons, which together confer robustness on neuronal regulation.

BackgroundThe association between elevated serum uric acid (UA) levels and the risk of developing colonic diverticulosis has not yet been investigated. Thus, this cross-sectional study aimed to examine this correlation in individuals from Taiwan.MethodsFrom Jan. 1, 2010, to Dec. 31, 2016., approximately 5,605 patients (aged >20 years) from Tri-Service General Hospital who met the inclusion criteria according to colonoscopy and laboratory test findings were included in this research. The correlation between serum UA levels and colonic diverticulosis was investigated via regression analyses.ResultsParticipants with elevated serum UA levels were at a higher risk of colonic diverticulosis. The area under the curve for serum UA levels was significantly higher in women than in men (0.651 [95% confidence interval: 0.596-0.707] vs. 0.55 [0.507-0.593]). There were specific trends in female-specific indicators for colonic diverticulosis across increasing quartiles of serum UA levels.ConclusionsPatients with elevated serum UA levels should be cautious regarding the development of colonic diverticulosis disorder in female. Moreover, prospective studies may provide additional information on the relationship between elevated serum UA levels and colonic diverticulosis.

Abstract Objective This study aimed to investigate the function and mechanism of neddylation of HDAC1 underlying drug resistance of AML cells. Methods Evaluation experiments of effects of HDAC1 on drug resistance of AML cells were performed with AML cell transfected with constructs overexpressing HDAC1 or multi-drug resistance AML cells transfected with siRNA for HDAC1 through observing cell viability, percentage of apoptotic cell, doxorubicin-releasing index and multidrug resistance associated protein 1 (MRP1) expression. Neddylation or ubiquitination of HDAC1 was determined by immunoprecipitation or Ni2+ pull down assay followed by western blot. The role of HDAC1 was in vivo confirmed by xenograft in mice. Results HDAC1 was significantly upregulated in refractory AML patients, and in drug-resistant AML cells (HL-60/ADM and K562/A02). Intracellular HDAC1 expression promoted doxorubicin resistance of HL-60, K562, and primary bone marrow cells (BMCs) of remission AML patients as shown by increasing cell viability and doxorubicin-releasing index, inhibiting cell apoptosis. Moreover, HDAC1 protein level in AML cells was regulated by the Nedd8-mediated neddylation and ubiquitination, which further promoted HDAC1 degradation. In vivo, HDAC1 overexpression significantly increased doxorubicin resistance; while HDACs inhibitor Panobinostat markedly improved the inhibitory effect of doxorubicin on tumor growth. Furthermore, HDAC1 silencing by Panobinostat and/or lentivirus mediated RNA interference against HDAC1 effectively reduced doxorubicin resistance, resulting in the inhibition of tumor growth in AML bearing mice. Conclusion Our findings suggested that HDAC1 contributed to the multidrug resistance of AML and its function turnover was regulated, at least in part, by post-translational modifications, including neddylation and ubiquitination.

Abstract Background To examine the influence of HOXD10 on the metabolism and growth of colon carcinoma cells by suppressing the RHOC/AKT/MAPK pathway. Methods Thirty-seven paired colon cancer and its adjacent samples from The Cancer Genome Atlas (TCGA) were analyzed. Chip Analysis Methylation Pipeline (ChAMP) analysis was employed for differential methylated points (DMPs) and the differential methylation regions (DMRs) screening. The HOXD10 mRNA expression and DNA methylation levels were detected by RT-PCR. The Cell proliferation, migration, invasion and apoptosis were respectively measured by MTT assay, transwell assay, wound healing assay and flow cytometry assay in carcinoma cell lines after treated with 5-aza-2′-deoxycytidine (5-Aza-dC) or transfected with HOXD10-expressing plasmid. The expression of HOXD10 and RHOC was revealed by immunohistochemistry in disparate differentiation colon carcinoma tissues, and the dephosphorylation of AKT and MAPK pathways were detected by RT-PCR and western blot. Results The bioinformatics analysis demonstrated that HOXD10 was hypermethylated and low-expressed in colorectal cancer tissues. The detection of RT-PCR indicated the similar results in colorectal cancer cell lines and tissues. The induction of demethylation was recovered by treatment with 5-Aza-dC and the HOXD10 in colorectal cancer cell lines was re-expressed by transfection with a HOXD10 expression vector. The demethylation or overexpression of HOXD10 suppressed proliferation, migration, invasion and promoted apoptosis in colorectal cancer cells. HXOD10 suppressed the tumor growth and detected an opposite trend of protein RHOC. AKT and MAPK pathways were notably inactivated after the dephosphorylation due to the overexpression of HOXD10. Conclusions HOXD10 was suppressed in colon adenocarcinoma cells, which down-regulated RHOC/AKT/MAPK pathway to enhance colon cancer cells apoptosis and constrain the proliferation, migration and invasion.

Objectives This study examined the associations between the Second-Generation Cessation Payment Scheme (SCPS) and the use of smoking cessation treatments. Furthermore, these associations were compared between light and heavy smokers in Taiwan.Design This study had a cross-sectional design.Setting Data were obtained from the Taiwan Adult Smoking Behaviour Surveillance System 2010–2011 and 2013–2014; data for each year consisted of a nationally representative sample of adults aged 18 years and older.Participants Current smokers who had either quit or made a serious attempt to quit smoking were selected for the analysis.Primary outcome measure The primary outcome measure was the use of a smoking cessation clinic or pharmacy in a twice daily to quit smoking.Results According to multivariate analysis, the SCPS was positively associated with the combined use of a smoking cessation clinic and a pharmacy (OR=3.947; 95% CI: 1.359 to 11.463) when individual-level predictors (gender, age, education level, marital status, monthly household income, daily cigarette consumption, smoking status and self-reported health) were controlled. Heavy smokers showed a significant increase in the sole use of a pharmacy (OR=1.676; 95% CI: 1.094 to 2.569) and combined use of a smoking cessation clinic and pharmacy (OR=8.984; 95% CI: 1.914 to 42.173) after the SCPS was introduced. In addition, when related factors were controlled, the use of smoking cessation services was more frequent among heavy smokers than light smokers, including any treatment (OR=1.594; 95% CI: 1.308 to 1.942), a smoking cessation clinic (OR=1.539; 95% CI: 1.232 to 1.922), a pharmacy (OR=1.632; 95% CI: 1.157 to 2.302) and the combination of a smoking cessation clinic and pharmacy (OR=4.608; 95% CI: 1.331 to 15.949) .Conclusions The SCPS subsidisation policy increased the use of smoking cessation treatments, particularly among heavy smokers.

BackgroundProcalcitonin (PCT) has been widely investigated as an infection biomarker. The study aimed to prove that serum PCT, combining with other relevant variables, has an even better sepsis-detecting ability in critically ill patients.MethodsWe conducted a retrospective cohort study in a regional teaching hospital enrolling eligible patients admitted to intensive care units (ICU) between July 1, 2016, and December 31, 2016, and followed them until March 31, 2017. The primary outcome measurement was the occurrence of sepsis. We used multivariate logistic regression analysis to determine the independent factors for sepsis and constructed a novel PCT-based score containing these factors. The area under the receiver operating characteristics curve (AUROC) was applied to evaluate sepsis-detecting abilities. Finally, we validated the score using a validation cohort.ResultsA total of 258 critically ill patients (70.9±16.3 years; 55.4% man) were enrolled in the derivation cohort and further subgrouped into the sepsis group (n = 115) and the non-sepsis group (n = 143). By using the multivariate logistic regression analysis, we disclosed five independent factors for detecting sepsis, namely, "serum PCT level," "albumin level" and "neutrophil-lymphocyte ratio" at ICU admission, along with "diabetes mellitus," and "with vasopressor." We subsequently constructed a PCT-based score containing the five weighted factors. The PCT-based score performed well in detecting sepsis with the cut-points of 8 points (AUROC 0.80; 95% confidence interval (CI) 0.74-0.85; sensitivity 0.70; specificity 0.76), which was better than PCT alone, C-reactive protein and infection probability score. The findings were confirmed using an independent validation cohort (n = 72, 69.2±16.7 years, 62.5% men) (cut-point: 8 points; AUROC, 0.79; 95% CI 0.69-0.90; sensitivity 0.64; specificity 0.87).ConclusionsWe proposed a novel PCT-based score that performs better in detecting sepsis than serum PCT levels alone, C-reactive protein, and infection probability score.

The population with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) is increasing. However, no medicine is indicated for treating these diseases clinically nowadays. Therefore, there is an urgent need to develop a new drug to overcome NAFLD and NASH. Capillarisin, a 2-phenoxychromone originating from Artemisia capillaris Thunb., is well-known for its liver-protective effects. As a result, a series of 2-phenoxychromones was prepared and evaluated for its protective activity against lipid droplet formation in oleic acid (OA)-treated Huh7 cells by means of high-content screening. In the light of the results, the compounds with trimethoxy groups on the phenyl ring possessed better inhibitory properties against lipid accumulation in Huh7 cells, compared to other functional groups on the same ring. Nonetheless, the compounds with a hydroxy group at the C-5 position of the chromone exhibited apparent cytotoxicity. Finally, the active compound, 5,7-dimethoxy-2-(3,4,5-trimethoxyphenoxy)-chromen-4-one (7e), with an IC50 value of 32.2 ± 2.1 μM against lipid accumulation and no significant cytotoxicity, reduced the accumulation of lipid droplets by up-regulating peroxisome proliferator-activated receptor gamma coactivator 1α (PGC1α) to facilitate the catabolism of fat, which shows promise for further optimization to manage NAFLD and NASH.

Epiphytic bryophytes (EB) are some of the most commonly found plant species in tropical montane cloud forests, and they play a disproportionate role in influencing the terrestrial hydrological and nutrient cycles. However, it is difficult to estimate the abundance of EB due to the nature of their “epiphytic” habitat. This study proposes an allometric scaling approach implemented in twenty-one 30 × 30 m plots across an elevation range in 16,773 ha tropical montane cloud forests of northeastern Taiwan to measure EB biomass, a primary metric for indicating plant abundance and productivity. A general allometry was developed to estimate EB biomass of 100 cm2 circular-shaped mats (n = 131) with their central depths. We developed a new point-intercept instrument to rapidly measure the depths of EB along tree trunks below 300 cm from the ground level (sampled stem surface area (SSA)) (n = 210). Biomass of EB of each point measure was derived using the general allometry and was aggregated across each SSA, and its performance was evaluated. Total EB biomass of a tree was estimated by referring to an in-situ conversion model and was interpolated for all trees in the plots (n = 1451). Finally, we assessed EB biomass density at the plot scale of the study region. The general EB biomass-depth allometry showed that the depth of an EB mat was a salient variable for biomass estimation (R2 = 0.72, p < 0.001). The performance of upscaling from mats to SSA was satisfactory, which allowed us to further estimate mean (±standard deviation) EB biomass of the 21 plots (272 ± 104 kg ha−1). Since a significant relationship between tree size and EB abundance is commonly found, regional EB biomass may be mapped by integrating our method and three-dimensional remotely sensed airborne data.

The ternary chalcogenide Cu3VSe4 (CVSe) with sulvanite structure has been theoretically predicted to be a promising candidate for photovoltaic applications due to its suitable bandgap for solar absorption and the relatively earth-abundant elements in its composition. To realize the absorber layer via an inexpensive route, printed thin-films could be fabricated from dispersions of nano-sized Cu3VSe4 precursors. Herein, cubic Cu3VSe4 nanocrystals were successfully synthesized via a hot-injection method. Similar with reported Cu3VS4 nanocrystals, Cu3VSe4 nanocrystals with cubic structure exhibit three absorption bands in the UV-Visible range indicative of a potential intermediate bandgap existence. A thin film fabricated by depositing the nanoparticles Cu3VSe4 on FTO coated glass substrate, exhibited a p-type behavior and a photocurrent of ~ 4 μA/cm2 when measured in an electrochemical cell setting. This first demonstration of photocurrent exhibited by a CVSe nanocrystals thin film signifies a promising potential in photovoltaic applications.

BackgroundAircrew members are required to attend hypoxia awareness training regularly to strengthen their memory of their personal hypoxia symptoms by undergoing training inside a hypobaric chamber. The aim of this study was to examine the association between hypoxia symptoms experienced during two training sessions that were 4 years apart.MethodsThis was a crossover study to compare hypoxia symptoms and self-reported physiological effects of trapped gas between a previous training session and a current training session in an altitude chamber. The subjects were military crew members who undertook a 25,000-feet refresher training course in 2018. We used a structured questionnaire to obtain the target information before and during hypoxia exposure. Data were analyzed using SPSS software.ResultsA total of 341 trainees participated in this survey and completely filled out the questionnaire. Gastrointestinal tract discomfort caused by the expansion of trapped gas was the main physiological reaction during the previous and current training sessions. Frequently reported symptoms were poor concentration (30.5%), impaired cognitive function (20.5%), visual disturbances (16.4%), hot flashes (15.8%), and paresthesia (12.6%) during both exposures. However, the proportions of participants reporting poor concentration (P = 0.378) and visual disturbances (P = 0.594) were not significantly different between the recalled and current training sessions. The five most common symptoms among the subjects with less than 1,000 flight hours were poor concentration (29.8%), visual disturbance (27.3%), impaired cognitive function (14.9%), dizziness/lightheadedness (11.6%), and hot flashes (9.9%), which overlapped substantially with the symptoms reported by other subjects. The occurrence of those five most common symptoms in the group with more than 1,000 flight hours did not significantly differ between the recalled training session and the current training session.ConclusionsThe most common hypoxia symptoms reported were similar between the recalled and current training sessions in an environment with a low oxygen concentration. This finding was also clearly affected by the duration of flight experience. Moreover, GI effects of the expansion of trapped gas were commonly observed at low atmospheric pressure.

Abstract Background Bladder cancer (BCa) is one of the most common cancers in the urinary system among the world. Previous studies suggested that TMEM40 expression level was significantly associated with clinicopathological parameters including histological grade, clinical stage and pT status of bladder cancer. However, the molecular mechanism of TMEM40 in BCa remains poorly understood. Methods Real-time quantitative RT-PCR (qRT-PCR) and western blot (WB) were used to examine the expression levels of TMEM40 in BCa tissues, paired non-cancer tissues and cell lines. A series of experiments, including CCK-8, wound healing, flow cytometry, transwell and EdU assays were performed to assess the effects of TMEM40 on cell proliferation, cell cycle and apoptosis, migration and invasion. In addition, tumor growth was evaluated in vivo using a xenogenous subcutaneously implant model. All statistical analyses were executed by using the SPSS 20.0 software. All experimental data from three independent experiments were analyzed by Student’s t test and results were expressed as mean ± standard deviation. Results In this study, we identified the role of TMEM40 in the tumorigenesis of bladder cancer and found that it was upregulated in bladder cancer tissues and cell lines, compared with their normal counterparts. The results demonstrated that effective silence of TMEM40 expression suppressed cell proliferation, blocked G1-to-S cell cycle transition, and inhibited cell migration and invasion in human bladder 5637 and EJ cell lines. Consistently, in vivo data showed that TMEM40 silencing could dramatically decreased tumor growth. Further study revealed that TMEM40 knockdown resulted in accumulation of p53 and p21 protein and decrease of c-MYC and cyclin D1 protein. Conclusion These data suggest that TMEM40 represents a potential oncogene, which exert a crucial role in the proliferation and apoptosis via the p53 signaling pathway in BCa, thus probably serve as a novel candidate biomarker and a potential therapeutic target for patients with BCa.

The purpose of the study was to examine the leisure constraints and job satisfaction of middle-aged and elderly health care workers. The study employed a mixed research method, utilizing SPSS 22.0 and AMOS 23.0 statistical software to analyze 260 questionnaires using basic statistical tests, t-tests, ANOVA tests, and structural equation models, and then interviewed medical and public health workers and experts in the field, and the results were analyzed using multivariate verification analysis. The results showed that there was a significant low correlation between leisure constraints and job satisfaction among middle-aged and elderly health care workers (p < 0.01); interpersonal constraints and external job satisfaction factors were the main influencing factors; improving promotion opportunities and receiving appreciation increased job satisfaction; poor working environment and facilities, as well as the lack of achievement, were the main factors that reduced satisfaction; health factors, a lack of family support, no exercise partner, and a lack of extra budget are the key to leisure constraints. If the organization can provide nearby sports facilities for middle and high-age medical workers, improve welfare, and increase willingness to participate in leisure activities, physical and mental health can be improved. Finally, interpersonal interaction in leisure obstacles is the main reason for improving job satisfaction.

Abstract 1.5-μm AlN grown by metal-organic chemical vapor deposition (MOCVD), with a single substrate temperature of 1180 °C, exhibits atomically flat surface and the XRD (102) peak width of 427 arcsec. The results are achieved with a pulsed NH3-flow condition, serving as an alternative for the commonly used temperature-varied buffer structure, which is often complicated and time-consuming. Inserting two pulsed-NH3-flow AlN layers in the epitaxial structure not only releases the lattice strain via the formation of three-dimensional nano-islands, but also smoothens the surface with prolonged lateral migration of Al adatoms. This effective growth technique substantially simplifies the manufacture of device-quality AlN.

The chain of survival has been shown to improve the chances of survival for victims of cardiac arrest. Post-cardiac arrest care has been demonstrated to significantly impact the survival of out-of-hospital cardiac arrest (OHCA). How post-cardiac arrest care influences the survival of OHCA patients has been a main concern in recent years. The objective of this study was to assess the survival outcome of hospitalized OHCA patients and determine the factors associated with improved survival in terms of survival to discharge. We conducted a retrospective observational study by analyzing records from the National Health Insurance Research Database of Taiwan from 2007 to 2013. We collected cases with an International Classification of Disease Clinical Modification, 9th revision primary diagnosis codes of 427.41 (ventricular fibrillation, VF) or 427.5 (cardiac arrest) and excluded patients less than 18 years old, as well as cases with an unknown outcome or a combination of traumatic comorbidities. We then calculated the proportion of survival to discharge among hospitalized OHCA patients. Factors associated with the dependent variable were examined by logistic regression. Statistical analysis was conducted using SPSS 22 (IBM, Armonk, NY). Of the 11,000 cases, 2,499 patients (22.7%) survived to hospital discharge. The mean age of subjects who survived to hospital discharge and those who did not was 66.7±16.7 and 71.7±15.2 years, respectively. After adjusting for covariates, neurological failure, cardiac comorbidities, hospital level, intensive care unit beds, transfer to another hospital, and length of hospital stay were independent predictors of improved survival. Cardiac rhythm on admission was a strong factor associated with survival to discharge (VF vs. non-VF: adjusted odds ratio: 3.51; 95% confidence interval: 3.06-4.01). In conclusion, cardiac comorbidities, hospital volume, cardiac rhythm on admission, transfer to another hospital and length of hospital stay had a significant positive association with survival to discharge in hospitalized OHCA patients in Taiwan.

The changes in and relationship between oxidative stress and the glutathione (GSH) antioxidant system in the plasma and tissues of patients with hepatocellular carcinoma (HCC) before and after tumor resection have not been clearly determined. We investigated the changes in oxidative stress, GSH status and its dependent antioxidant enzyme activities in HCC patients before and after tumor resection, and to determine the association of oxidative stress with GSH and its dependent antioxidant enzyme activities in plasma and tissues. This study employed a cross-sectional design. Forty-four men and 16 women with HCC were recruited. Fasting blood was drawn on the day before the tumor resection and one month after the tumor resection. HCC tissue and adjacent normal liver tissue were obtained at the time of surgical resection. Patients had significantly increased plasma malondialdehyde (MDA) and oxidized-low density lipoprotein levels but decreased GSH and oxidized GSH levels before tumor resection compared with the corresponding post-resection values. GSH and trolox equivalent antioxidant capacity (TEAC) levels and activities of GSH peroxidase were significantly increased while MDA level was significantly lower in HCC tissue when compared with the adjacent normal tissue. The pre-resection plasma MDA level was significantly correlated with pre-resection plasma GSH concentration, and MDA level in HCC and adjacent normal tissues. Pre-resection plasma GSH concentration was significantly correlated with GSH and TEAC level in HCC tissue. HCC patients had increased oxidative stress, decreased GSH, and lower dependent antioxidant capacities before tumor resection. However, hepatocellular tumor had increased GSH and TEAC levels as well as GSH peroxidase activities which might protect itself against increased oxidative stress.

This study investigates the effects of five decontamination methods on the filter quality (qf) of three commercially available electret masks-N95, Gauze and Spunlace nonwoven masks. Newly developed evaluation methods, the overall filter quality (qf,o) and the qf ratio were applied to evaluate the effectiveness of decontamination methods for respirators. A scanning mobility particle sizer is utilized to measure the concentration of polydispersed particles with diameter 14.6-594 nm. The penetration of particles and pressure drop (Δp) through the mask are used to determine qf and qf,o. Experimental results reveal that the most penetrating particle size (MPS) for the pre-decontaminated N95, Gauze and Spunlace masks were 118 nm, 461 nm and 279 nm, respectively, and the respective penetration rates were 2.6%, 23.2% and 70.0%. The Δp through the pretreated N95 masks was 9.2 mm H2O at the breathing flow rate of heavy-duty workers, exceeding the Δp values obtained through Gauze and Spunlace masks. Decontamination increased the sizes of the most penetrating particles, changing the qf values of all of the masks: qf fell as particle size increased because the penetration increased. Bleach increased the Δp of N95, but destroyed the Gauze mask. However, the use of an autoclave reduces the Δp values of both the N95 and the Gauze mask. Neither the rice cooker nor ethanol altered the Δp of the Gauze mask. Chemical decontamination methods reduced the qf,o values for the three electret masks. The value of qf,o for PM0.1 exceeded that for PM0.1-0.6, because particles smaller than 100 nm had lower penetration, resulting in a better qf for a given pressure drop. The values of qf,o, particularly for PM0.1, reveal that for the tested treatments and masks, physical decontamination methods are less destructive to the filter than chemical methods. Nevertheless, when purchasing new or reusing FFRs, penetration should be regarded as the priority.

Stenotrophomonas maltophilia, a gram-negative bacterium, has increasingly emerged as an important nosocomial pathogen. It is well-known for resistance to a variety of antimicrobial agents including cationic antimicrobial polypeptides (CAPs). Resistance to polymyxin B, a kind of CAPs, is known to be controlled by the two-component system PhoPQ. To unravel the role of PhoPQ in polymyxin B resistance of S. maltophilia, a phoP mutant was constructed. We found MICs of polymyxin B, chloramphenicol, ampicillin, gentamicin, kanamycin, streptomycin and spectinomycin decreased 2-64 fold in the phoP mutant. Complementation of the phoP mutant by the wild-type phoP gene restored all of the MICs to the wild type levels. Expression of PhoP was shown to be autoregulated and responsive to Mg2+ levels. The polymyxin B and gentamicin killing tests indicated that pretreatment of low Mg2+ can protect the wild-type S. maltophilia from killing but not phoP mutant. Interestingly, we found phoP mutant had a decrease in expression of SmeZ, an efflux transporter protein for aminoglycosides in S. maltophilia. Moreover, phoP mutant showed increased permeability in the cell membrane relative to the wild-type. In summary, we demonstrated the two-component regulator PhoP of S. maltophilia is involved in antimicrobial susceptibilities and low Mg2+ serves as a signal for triggering the pathway. Both the alteration in membrane permeability and downregulation of SmeZ efflux transporter in the phoP mutant contributed to the increased drug susceptibilities of S. maltophilia, in particular for aminoglycosides. This is the first report to describe the role of the Mg2+-sensing PhoP signaling pathway of S. maltophilia in regulation of the SmeZ efflux transporter and in antimicrobial susceptibilities. This study suggests PhoPQ TCS may serve as a target for development of antimicrobial agents against multidrug-resistant S. maltophilia.