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Background Anti-interleukin-5 (IL-5) therapy has been proposed as a novel treatment option for patients with chronic obstructive pulmonary disease (COPD). However, its efficacy for preventing COPD exacerbation remains unclear. Methods A literature review was conducted to August 26th 2019. Only randomized controlled trials (RCTs) that investigated the clinical efficacy and adverse effects of anti-IL-5 therapy were included in the meta-analysis. The primary outcome was the risk of COPD exacerbation. Results A total of 3 articles containing 5 RCTs were included in the study. Overall, 2837 and 1442 patients received anti-IL-5 therapy (mepolizumab, n = 865; benralizumab, n = 1972) and placebo, respectively. In the pooled analysis, anti-IL-5 therapy was associated with a lower risk of COPD exacerbation compared with the placebo (rate ratio, 0.92; 95% CI, 0.86–0.97, I2 = 0%). In addition, no significant differences in the changes in SGRQ scores and FEV1 from baseline were found between the anti-IL-5 therapy and placebo (SGRQ, mean difference, −0.86, 95% CI, −1.92 – 0.19, I2 = 0%; FEV1, mean difference, 0.01, 95% CI, −0.01 – 0.03, I2 = 0%). Anti-IL-5 therapy had a similar risk of any adverse event (risk ratio, 1.02; 95% CI, 0.99–1.05), an event leading to treatment discontinuation (risk ratio, 1.04; 95% CI, 0.72–1.48) and any serious adverse events (risk ratio, 0.93; 95% CI, 0.85–1.01) when compared with the placebo. Conclusion Anti-IL-5 therapy was associated with a lower rate of COPD exacerbation compared with placebo. In addition, anti-IL-5 therapy was well tolerated for COPD patients.

Purpose The aim of this meta-analysis is to compare the clinical efficacy and safety of baloxavir with other anti-influenza agents or placebo in the treatment of influenza. Methods PubMed, Embase, Web of Science, Google Scholar, Scopus, CINAHL, Cochrane databases and clinical registration were searched from inception until February 15 2021 for relevant randomized controlled trials (RCTs). Only phase 3 RCTs evaluating the usefulness of baloxavir in the treatment of influenza were included. Results Three RCTs enrolling 3771 patients (baloxavir group, n = 1451; oseltamivir group, n = 1288; placebo group, n = 1032) were included. Compared with oseltamivir, baloxavir had an insignificantly shorter time to the alleviation of symptoms (mean difference [MD], −1.29 h; 95% CI, −6.80 to 4.21; I2 = 0%). In contrast, baloxavir had a significantly shorter time to the alleviation of symptoms than placebo (MD, −26.32 h; 95% CI, −33.78 to −18.86; I2 = 0%). Baloxavir was associated with a significant decline in influenza virus titers and viral RNA load compared to oseltamivir and placebo. Baloxavir was associated with a lower risk of any adverse events than oseltamivir (OR, 0.82; 95% CI, 0.69–0.98; I2 = 0%) and placebo (OR, 0.79; 95% CI, 0.66–0.96; I2 = 0%). Conclusions The findings of this meta-analysis suggested that baloxavir is superior to placebo in the treatment of influenza in both clinical outcome and virological response. Moreover, baloxavir was found to have a better virological response than oseltamivir and to be as effective as oseltamivir clinically. Compared with oseltamivir and placebo, baloxavir appears to be a relatively safe anti-influenza agent.

Utilization of rhizosphere microorganisms to improve plant growth and salt tolerance has recently attracted widespread attention. The growth and salt tolerance of willows inoculated with Bacillus cereus JYZ-SD2 and Peniophora cinerea XC were studied under different salt stress conditions. The results showed that the chlorophyll content of willow cuttings inoculated with the XC strain increased significantly by 51.27%. After salt stress of willow cuttings inoculated with B. cereus JYZ-SD2 and P. cinerea XC (solely or in combination), the amount of sodium in the roots from the epidermis to the pericycle decreased and the content of sodium in the pericycle was significantly lower than that of the uninoculated willow, while the proportion of potassium increased. Willow cuttings inoculated with microorganisms showed increased activity of SOD and POD. At the salt concentration of 100 mmol/L, the highest SOD activity was found in B. cereus JYZ-SD2-inoculated willows, with 59.88% increase compared to uninoculated willows; the highest POD activity was found in P. cinerea XC and B. cereus JYZ-SD2 co-inoculated willows, with 51.05% increase compared to uninoculated willows. The Na-K-ATPase and Ca-Mg-ATPase activities of inoculated P. cinerea XC willow cuttings were also 59.38% and 60% higher than that of uninoculated willows, respectively. The qPCR analysis showed that the expression of vp2 gene in the microorganism-inoculated willow leaves was always higher than that in willow alone. The expression of vp2 gene in P. cinerea XC-inoculated willow cuttings was 270.81% higher than that in uninoculated willows. Further observation of the ultrastructure of root cells under salt stress revealed that most of the vesicles in the root tip cells of willow were intact and secreted phagocytic vesicles to absorb sodium ions in the cytoplasm. This study shows that the combined beneficial fungi and rhizosphere-promoting bacteria inoculation technology as a practical biotechnological approach to enhance the growth of willows in salt-affected soils.

Obstructive sleep apnea (OSA) is a chronic breathing disorder characterized by intermittent sleep state-dependent upper airway (UA) collapse. The tongue comprises the primary UA dilator muscle and plays an essential role in the pathogenesis of OSA. We examined whether tongue stiffness measurement using ultrasound (US) shear wave elastography (SWE) is useful for predicting the existence of OSA. Forty-six participants (20 healthy controls and 26 patients with OSA) underwent transcutaneous submental SWE using a US system. Quantification with a shear modulus of 0-200 kPa was recorded during normal breathing and Muller's maneuver (MM). Polysomnography was used as the reference standard. Mid-sagittal tongue stiffness was significantly higher in awake patients with OSA than in controls during normal breathing and the MM (p < 0.0001). The posterior third of the tongue in patients with OSA had the highest value of shear modulus during the MM (p < 0.001). With cut-offs of 27.6 and 35.2 kPa for the whole tongue and posterior third during the MM, respectively, the sensitivity obtained was 69.2% and 76.9%, and the specificity was 85% and 95%, respectively, for detecting OSA. The corresponding areas under the receiver operating characteristic curve were 0.82 and 0.88, respectively. US SWE may have the potential for non-invasive tongue stiffness measurement in OSA.

This work analyzes the operation conditions of the wavy-tilt-dam (WTD) mechanical seal under different structural parameters using the DNS method. The pressure difference within the liquid film is considered due to the complicated constructor of the WTD mechanical seal. The effects of the main structural parameters on the mechanical seal are studied, including the film thickness, taper, dam-width ratio, and waviness amplitude. Numerical results show that the increase of base film thickness will increase the leakage rate and decrease the opening force. The larger taper will lead to a higher leakage rate and opening force. As the taper increases, the stiffness increases first and then decreases. As the dam-width ratio increases, the leakage rate, the opening force, and the stiffness will increase correspondingly. The waviness amplitude has a small effect on these three performance parameters. Besides, the comparisons between the Reynolds approximation and the DNS technique show that the Reynolds approximation can be applied to analyze the leakage rate under different thicknesses, small tapers, and large dam-width ratios. The opening force under small thickness, different tapers, and different dam-width ratios can also be considered using the Reynolds approximation. To ensure the safe and stable operation of RCP, the optimal structural parameters can be set as taper β = 600 μrad, dam-width ratio ϖ = 0.2, waviness amplitude α = 0.8, and wavenumber k = 9.

The phytochrome-interacting factor (PIF) subfamily of basic helix-loop-helix (bHLH) transcription factors plays a critical role in plant growth and development. However, there has been no detailed report on the PIFs in carrot. In this study, we present the identification and characterization of DcPIF gene family in carrot (Daucus carota L.). Phylogenetic analysis indicated that PIFs from carrot and other five plant species could be divided into four groups supported by similar gene structure and motif analysis. Expression profiles showed that all DcPIF genes were tissue-specific and could be induced by drought or abscisic acid (ABA) treatment except DcPIF7.1, among which DcPIF3 was the most responsive. The DcPIF3-overexpressed Arabidopsis plants exhibited more tolerance to drought stress, with higher antioxidant capacity and lower malondialdehyde content after drought treatment than wild type plants. Further stress tolerance assays revealed that DcPIF3 plays a positive role in drought stress by increasing endogenous ABA level and promoting the expression of ABA-related genes. Our results can enrich the understanding of DcPIF family genes and lay a foundation for further investigation of DcPIF3 function to defend against drought stress in carrot.

In this study, a Standard Operating Procedure (SOP) for the large-scale extraction, enrichment, and separation of suffruticosol B (SB), trans-ε-Viniferin (TV), trans-gnetin H (TG) from oil tree peony seeds shell (PSS) was successfully constructed. The ultrasonic-assisted extraction (UAE), macroporous adsorption resin (MAR), and column chromatography (CC) were employed to extract, enrich and separate SB, TV and TG from PSS, and the conditions were optimized. The results implied that SB (1.6937 g), TV (0.5884 g) and TG (3.8786 g) with the purity of 99.67 %, 99.32 % and 98.54 %, respectively, were obtained after the extraction, enrichment and separation. The total yields of the SB, TV and TG were 0.61 mg/g, 0.02 mg/g and 6.64 mg/g with the total extraction rates at 70.55 %, 69.77 % and 78.36 %, respectively. This is the first report on the large-scale extraction, enrichment and separation of oligostilbenes. The SOP in this paper could produce high purity SB, TV and TG, and provide a new idea for PSS as a new oligostilbene resource. The study expands the new development and research field of PSS and provides theoretical support for the green utilization of oil tree peony.

Overuse of short-acting β-agonists (SABAs) could be associated with increased acute exacerbations and mortality in patients with asthma. However, the role of SABAs in sepsis has not been well studied.We sought to investigate the association between the overuse of SABAs and sepsis in patients with asthma.Between 2001 and 2013, patients with asthma were identified from Taiwan asthma pay-for-performance program database, but patients with prior sepsis were excluded. The overuse of SABAs was defined as the use of 3 or more canisters annually.A total of 28,033 patients were found to have overused SABAs (overuse group), and 155,453 patients had acceptable use of SABAs (control group). Using propensity score matching method with 1:1 ratio, we had 2 subgroups with similar baseline characteristic and each group had 20,542 patients. The incidence of sepsis during the follow-up period was 1.26 per 100 person-years in the SABA overuse group, which was higher than in the control group (0.94 per 100 person-years). The crude and adjusted hazard ratios were 1.35 (95% CI, 1.26-1.44) and 1.33 (95% CI, 1.24-1.43), respectively. The SABA overuse group also had a higher risk of sepsis within 1 year than the control group (adjusted odds ratio, 1.34; 95% CI, 1.09-1.64). The incidence of septic shock during the follow-up period was 0.44 per 100 person-years in the SABA overuse group, which was higher than in the control group (0.33 per 100 person-years). The crude and adjusted hazard ratios were 1.32 (95% CI, 1.17-1.48) and 1.28 (95% CI, 1.14-1.44), respectively. Subgroup analysis consistently revealed a higher incidence of sepsis in the SABA overuse group than in the control group in all age and male groups before and after propensity score matching.The overuse of SABA could be associated with an increased risk of sepsis and septic shock in the patient with asthma in Taiwan.

Acetyl-CoA synthetase 2 (ACSS2) generates acetyl-CoA from acetate is important for histone acetylation and gene expression. ACSS2 fulfills distinct functions depending on its cellular location in tumor cells. The role and cellular localization of ACSS2 in hepatocellular carcinoma (HCC) remains to be studied. Herein, we identified that the alternative transcription start site selection of ACSS2 was significantly different between HCC and corresponding adjacent tissues. Alternative transcription start site selection produced two different ACSS2 transcripts, ACSS2-S1 and ACSS2-S2. The two isoforms of ACSS2 had different subcellular localization and different functions. Overexpression of ACSS2-S2 promoted cell proliferation and invasion, but ACSS2-S1 did not. The ACSS2-S1 was mainly present in cytoplasm, and ACSS2-S2 was distributed in both nucleus and cytoplasm. Finally, we demonstrated that alternative transcription start site selection of ACSS2 correlates ribosome biogenesis in HCC. Our findings reveal an oncogenic role of ACSS2-S2 in HCC progression via increase of ribosome biogenesis, and suggest ACSS2-S2 might be a potential therapeutic target against the HCC.

Background Hepatic fibrosis is caused by chronic liver injury and may progress toward liver cirrhosis, and even hepatocellular carcinoma. However, current treatment is not satisfactory. Therefore, there is a mandate to find novel therapeutic targets to improve therapy, and biomarkers to monitor therapeutic response. Methods Liver fibrosis was induced by carbon tetrachloride (CCl4) or thioacetamide (TAA) in wild type (WT) or CTHRC1−/− mice, followed by immunofluorescence and immunohistochemical analyses. CTHRC1 monoclonal antibody (mAb) was used to abrogate the effect of CTHRC1 in vitro and in vivo. Results Here, we reported that collagen triple helix repeat containing 1 (CTHRC1), a secreted protein derived from hepatic stellate cells (HSCs), was significantly up-regulated in fibrotic liver tissues. CTHRC1 promoted HSCs transformation from a quiescent to an activated state, and enhanced migratory or contractile capacities of HSCs by activating TGF-β signaling. Meanwhile, CTHRC1 competitively bound to Wnt noncononical receptor and promoted the contractility but not activation of HSCs. CCl4 or TAA-induced liver fibrosis was attenuated in CTHRC−/− mice compared with littermate control, while a monoclonal antibody of CTHRC1 suppressed liver fibrosis in WT mice treated with CCl4 or TAA. Interpretation We demonstrated that CTHRC1 is a new regulator of liver fibrosis by modulating TGF-β signaling. Targeting CTHRC1 could be a promising therapeutic approach, which can suppress TGF-β signaling and avoid the side effects caused by directly targeting TGF-β. CTHRC1 could also be a potential biomarker for monitoring response to anti-fibrotic therapy. Fund This study was supported by the National Natural Science Foundation of China (ID 81672358, 81871923, 81872242, 81802890), the Shanghai Municipal Education Commission—Gaofeng Clinical Medicine Grant Support (ID 20181708), the Natural Science Foundation of Shanghai (ID 17ZR1428300, 18ZR1436900), and Shanghai Municipal Health Bureau (ID 2018BR32). The funders did not play a role in manuscript design, data collection, data analysis, interpretation nor writing of the manuscript.

Background Accumulating evidence has revealed the pivotal role of epigenetic regulation in the pathogenesis of liver disease. However, the epigenetic mechanism that accounts for hepatic stellate cells (HSCs) activation in liver fibrosis remains largely unknown. Methods Primary HSCs were used to screen the differentially expressed histone H3 lysine methyltransferases and demethylases during HSC activation. Loss-of-function experiments were applied to determine the cellular functions of KDM4D in HSCs. Transcriptome analysis was applied to explore the downstream targets of KDM4D. Real-time qPCR, western blotting, immunohistochemical staining, and chromatin immunoprecipitation were performed to uncover the underlying mechanism concerning KDM4D during liver fibrogenesis. Findings KDM4D was identified as a remarkable up-regulated histone H3 demethylase during HSC activation. The overexpression profile of KDM4D was confirmed in three fibrosis animal models and human fibrotic liver tissues. In vitro Kdm4d knockdown impaired the collagen gel contraction and migration capacity of primary HSCs. In established CCl4-induced mice model, Kdm4d knockdown inhibited fibrosis progression, and promoted fibrosis reversal, with enhanced thinning and splitting of fibrotic septa, as well as a dramatic decrease in collagen area. Whole gene transcriptome analysis showed the regulatory role of KDM4D in Toll-Like Receptor (TLR) signaling pathway. Mechanistically, KDM4D catalyzed histone 3 on lysine 9 (H3K9) di-, and tri-demethylation, which promoted TLR4 expression, and subsequently prompted liver fibrogenesis by activating NF-κB signaling pathways. Interpretation KDM4D facilitates TLR4 transcription through demethylation of H3K9, thus activating TLR4/NF-κB signaling pathways in HSCs, contributing to HSC activation and collagen crosslinking, further, hepatic fibrosis progression. Fund Shanghai New Hundred Talents Program, Shanghai Municipal Commission of Health and Family Planning, Key Developing Disciplines Program, Shanghai Key disciplines program of Health and Family Planning and Shanghai Sailing Program.

Repeated, recreational ketamine (KE) or methamphetamine (MA) administration seldom produce neurotoxicity, while combining MA and KE administration have been thought to render changes in neural plasticity and motivational behavior. In this study, we sought to assess whether pre-exposure to multiple MA injections and withdrawal may affect low-dose KE-produced rewarding effects, social interaction behavior and its neurochemical underpinnings. A 10-day MA injections (2 mg/kg/day) and 10-day withdrawal regimen was found to cause reliable behavioral sensitization. While KE (1 mg/kg) induced weak conditioned place preference (CPP), pre-exposure to this MA-withdrawal regimen enhanced such KE CPP magnitude. This MA-withdrawal regimen also caused impairments in the social interaction behavior in the sociability, social novelty test. Compared with the mice undergoing the 10-day saline-withdrawal or MA regimen, mice receiving the 10-day MA-withdrawal regimen exhibited lower dopamine-releasing probability in the nucleus accumbens, inferring the MA-withdrawal regimen-primed preference for KE rewarding effects. Likewise, mice receiving the MA-withdrawal regimen had high expression in mGluR5 protein but unaltered EAAT3, Homer2 expression in hippocampal tissues. Pretreatment with MPEP, an mGluR5 antagonist, prevented the MA-withdrawal regimen-induced increment in the KE CPP magnitude and impairments in social interaction behavior. We, thus, conclude that repeated MA administration and abstinence may enhance KE rewarding effects and produce eminent deficits in social recognition and interest. And these effects correlate with the mGluR5 over-expression and modulation of the KE-stimulating effect on dopamine release.

Highlights • As of 29 Feb. 2020, COVID-19 has affected 85 403 patients in 57 countries/territories and caused 2924 deaths in 9 countries. • The incidence (per 1 000 000 people) ranged from 61.4 in Republic of Korea to 0.0002 in India. • Daily cumulative index (DCI) of COVID-19 (cumulative cases/no. of days between first reported case and 29 Feb. 2020) was greatest in China (1320.85). • High DCIs were also seen in the Republic of Korea (78.78), Iran (43.11) and Italy (30.62). • The incidence and mortality were correlated with the DCI., It has been 2 months since the first case of coronavirus disease 2019 (COVID-19) was reported in Wuhan, China. So far, COVID-19 has affected 85 403 patients in 57 countries/territories and has caused 2924 deaths in 9 countries. However, epidemiological data differ between countries. Although China had higher morbidity and mortality than other sites, the number of new daily cases in China has been lower than outside of China since 26 February 2020. The incidence ranged from 61.44 per 1 000 000 people in the Republic of Korea to 0.0002 per 1 000 000 people in India. The daily cumulative index (DCI) of COVID-19 (cumulative cases/no. of days between the first reported case and 29 February 2020) was greatest in China (1320.85), followed by the Republic of Korea (78.78), Iran (43.11) and Italy (30.62). However, the DCIs in other countries/territories were

Summary Introduction Numerous reports showed that nicotinamide N-methyltransferase (NNMT) plays important roles in the regulation of energy metabolism and in the synthesis of ATP, which indicates that the activity of NNMT may be associated with sport performance. Methods and results To test this speculation, we inhibited NNMT activity of the rats with N-methylnicotinamide (MNA) (MNA group), and observed the effects on the lactate threshold and the maximal blood lactate concentration, and on the performance in the competitions of anaerobic and aerobic endurance exercise, respectively. The results showed: (1) the workloads (% body weight) of the rats in the swimming have no significant differences between MNA group and control group when the lactate threshold appeared (4.54 ± 0.90 vs. 4.60 ± 1.06), and when the maximal exercise intensity (exhaustion) appeared (6.00 ± 0.54 vs. 6.00 ± 0.81); (2) the rats of MNA group showed highly significantly lowered blood lactate concentrations than those of the control group immediately after the swimming with the maximal workload (10.40 ± 1.39 vs. 11.67 ± 1.71 mmol/L), 2 min post-exercise (11.49 ± 1.38 vs. 12.82 ± 1.63 mmol/L) and 4 min post-exercise (12.84 ± 1.36 vs. 14.3 ± 1.54 mmol/L); (3) in the anaerobic endurance exercise competition, 8 rats of the MNA group while 16 of the control group entered the top 24 places in the rank; (4) in the anaerobic endurance exercise competition, the swimming durations from the beginning until exhaustion were not significantly different between the MNA group and the control group (345.37 ± 71.69 vs. 345.30 ± 72.02 min). Conclusion These results suggest that NNMT inhibition significantly impairs the performance in anaerobic endurance exercise but not in aerobic endurance exercise.

Aims To investigate a partnership intervention of the community-based and hospital-based home visit to improve patients' satisfaction. Methods A time series quasi-experimental quantitative design was used. The experimental group had “partnership intervention”, while the control group maintained routine home visits. Patient satisfaction was measured pre-intervention, six months and 12 months after the partnership intervention. Results Six and 12 months after partnership intervention, in the experimental group, items related to stabilizing disease conditions, improving daily living abilities, enhancing communication ability and providing relevant resources were significantly higher than pre-intervention. However, 12 months after the intervention, the influence of the intervention became weaken. Conclusions The partnership intervention can significantly improve patients' satisfaction with home visit service.

Background Infective endocarditis (IE) is uncommon in childhood. Its associated epidemiological characteristics in patients with congenital heart disease (CHD) remain unclear. Methods The study population included children born in Taiwan during the years 1997 to 2005 who were diagnosed as having CHD before 3years of age. All children were followed up until the end year of 2010, the diagnosis of infective endocarditis, or death. The demographic characteristics of patients with and without IE, the invasive procedures performed during 6months before the index date, the prophylactic antibiotics related to dental procedures, and in-hospital mortality were collected. Results Information of 24,729 children with CHD were retrieved for our analysis and 237 patients with newly diagnosed IE were identified. The incidence rate of IE in all CHD lesions was 11.13 per 10,000person-years. Taking ASD for reference, the following CHD lesions were at risk for IE: cyanotic CHD (adjusted OR, 9.58; 95% confidence interval, 5.38–17.05), endocardial cushion defect (ECD) (8.01; 2.73–23.50), Left-sided lesions (4.36; 1.90–10.01) and VSD (2.93; 1.64–5.23). Patients who underwent procedures have a higher risk of acquiring IE which include central venous catheter (CVC) insertion (3.17; 2.36–4.27), cardiac catheterization (3.74; 2.67–5.22), open-heart surgery (2.47; 1.61–3.77), valve surgery (3.20; 1.70–6.02), and shunt surgery (7.43; 2.36–23.41). However, dental procedures did not increase the risk of IE, irrespective of antibiotic usage. Conclusions The risk of IE varies markedly among CHD lesions in our study. Invasive heart procedures but not dental procedures, are more significantly associated with IE among children with CHD.

Compressed sensing theory based distributed video coding is one of the active topics in video coding research filed. In the compressed perception theory, the KSVD dictionary is usually used to achieve signal sparsity. In this paper,Based on the K-SVD algorithm, this paper proposes to apply the discriminative K-SVD (d-ksvd) algorithm to distributed compressed sensing video coding. We evaluate our method using the video in YUV format. It is verified by experiments that our method not only achieve better result of reconstruction but also save lot of time in terms of computing time.

Sphaeropsis shoot blight disease is caused by Sphaeropsis sapinea, a necrotrophic ascomycete pathogen. As severe damage and heavy losses from this disease have been documented in pine forests in many countries, an effective and environmentally friendly control strategy for Sphaeropsis shoot blight disease must be identified and the mechanisms involved determined. We performed research on the antagonism mechanism and biocontrol efficacy of Bacillus pumilus HR10 in plants because we found it to inhibit S. sapinea under in vitro laboratory conditions. The secondary metabolites secreted by HR10 led to mycelial deformities, delayed spore germination, and weakened mycelial growth of the pathogen. Additionally, the pathogen cell membrane was damaged, and mycelial cell content synthesis was disrupted by a HR10 culture filtrate. When HR10 colonized pine shoots, scanning electron microscopy indicated that it accumulated around the mycelium, reducing mycelial thickness, and assembled inside and outside of stomata, thus preventing pathogen hyphae from invading the needles. In a greenhouse experiment, HR10 exhibited a good preventive effect on Sphaeropsis shoot blight of Pinus massoniana, and 90% relative control was achieved by preventively spraying HR10 on pine shoots. The antagonistic substance was present in the 90% ammonium sulfate precipitate of a B. pumilus HR10 culture filtrate. Bacillus pumilus HR10 thus may be an effective and suitable biocontrol agent for shoot blight disease of pine. This study is the first report describing control of Sphaeropsis shoot blight disease by B. pumilus HR10 and illustrating how HR10 can efficiently protect P. massoniana from S. sapinea.

Abscisic acid-responsive element (ABRE)-binding factors (ABFs) are important transcription factors involved in various physiological processes in plants. Stomata are micro channels for water and gas exchange of plants. Previous researches have demonstrated that ABFs can modulate the stomatal development in some plants. However, little is known about stomata-related functions of ABFs in carrots. In our study, DcABF3, a gene encoding for ABF transcription factor, was isolated from carrot. The open reading frame of DcABF3 was 1329 bp, encoding 442 amino acids. Expression profiles of DcABF3 indicated that DcABF3 can respond to drought, salt or ABA treatment in carrots. Overexpressing DcABF3 in Arabidopsis led to the increase of stomatal density which caused severe water loss. Expression assay indicated that overexpression of DcABF3 caused high expression of stomatal development-related transcription factor genes, SPCH, FAMA, MUTE and SCRMs. Increased antioxidant enzyme activities and higher expression levels of stress-related genes were also found in transgenic lines after water deficit treatment. Changes in expression of ABA synthesis-related genes and AtABIs indicated the potential role of DcABF3 in ABA signaling pathway. Under the treatment of exogenous ABA, DcABF3-overexpression Arabidopsis seedlings exhibited increased root length and germination rate. Our findings demonstrated that heterologous overexpression of DcABF3 positively affected stomatal development and also reduced ABA sensitivity in transgenic Arabidopsis.

Virtual autopsy (VIRTOPSY) is a non-invasive examination for forensic practice. It can objectively and accurately reflect fractures, soft tissue injuries, wound extent, and organ damage and provides intuitive and powerful court evidence for forensic identification. In recent years, Chinese scholars have investigated the application of VIRTOPSY in forensic analysis of cause of death by collecting cadaveric imaging data representing different causes of death, including falls from height, traffic accidents, burning, drowning, and cardiovascular and cerebrovascular accidents. A cadaver imaging database was initially established. These efforts have promoted the development and application of VIRTOPSY in Chinese forensic practice. In this article, we reviewed some papers published in recent years in forensic science journals domestic and abroad to show the present VIRTOPSY by postmortem multi-slice computed tomography (PMCT) applications in china for forensic pathology.

Background: Hepatic fibrosis is caused by chronic liver injury and may progress toward liver cirrhosis, and even hepatocellular carcinoma. However, current treatment is not satisfactory. Therefore, there is a mandate to find novel therapeutic targets to improve therapy, and biomarkers to monitor therapeutic response. Methods: Liver fibrosis was induced by carbon tetrachloride (CCl4) or thioacetamide (TAA) in wild type (WT) or CTHRC1-/- mice, followed by immunofluorescence and immunohistochemical analyses. CTHRC1 monoclonal antibody (mAb) was used to abrogate the effect of CTHRC1 in vitro and in vivo. Results: Here, we reported that collagen triple helix repeat containing 1 (CTHRC1), a secreted protein derived from hepatic stellate cells (HSCs), was significantly up-regulated in fibrotic liver tissues. CTHRC1 promoted HSCs transformation from a quiescent to an activated state, and enhanced migratory or contractile capacities of HSCs by activating TGF-β signaling. CCl4 or TAA-induced liver fibrosis was attenuated in CTHRC-/- mice compared with littermate control, while a monoclonal antibody of CTHRC1 suppressed liver fibrosis in WT mice treated with CCl4 or TAA. Interpretation: We demonstrated that CTHRC1 is a new regulator of liver fibrosis by modulating TGF-β signaling. Targeting CTHRC1 could be a promising therapeutic approach, which can suppress TGF-β signaling and avoid the side effects caused by directly targeting TGF-β. CTHRC1 could also be a potential biomarker for monitoring response to anti-fibrotic therapy. Funding Statement: This study was supported by the National Natural Science Foundation of China (ID 81672358, 81871923, 81872242), the Shanghai Municipal Education Commission — Gaofeng Clinical Medicine Grant Support (ID 20181708), the Natural Science Foundation of Shanghai (ID 17ZR1428300), and Shanghai Municipal Health Bureau (ID 2018BR32). The funders did not play a role in manuscript design, data collection, data analysis, interpretation nor writing of the manuscript Declaration of Interests: The authors have declared that no conflict of interest exists. Ethics Approval Statement: All of the human materials were obtained with informed content, and protocols were approved by the ethical review committee of the World Health Organization Collaborating Center for Research in Human Production (authorized by the Shanghai Municipal Government). Mice were housed and manipulated according to protocols approved by the East China Normal University Animal Care Commission. All animals received humane care according to the criteria outlined in the “Guide for the Care and Use of Laboratory Animals” prepared by the National Academy of Sciences and published by the National Institutes of Health.

Accumulating evidence has revealed the pivotal role of epigenetic regulation in the pathogenesis of liver disease. However, the epigenetic mechanism that accounts for hepatic stellate cells (HSCs) activation in liver fibrosis remains largely unknown. In this study, primary HSCs were used to screen the differentially expressed histone H3 lysine methyltransferases and demethylases during HSC activation. KDM4D was identified as a remarkable up-regulated histone H3 demethylase during HSC activation. The overexpression profile of KDM4D was further confirmed in three fibrosis animal models and human fibrotic liver tissues. In vitro genetic silencing of Kdm4d impaired the collagen gel contraction and migration capacity of primary HSCs. In established CCl4- induced mice model, Kdm4d knockdown inhibited fibrosis progression, and promoted fibrosis reversal, with enhanced thinning and splitting of fibrotic septa, as well as a dramatic decrease in collagen area. Whole gene transcriptome analysis showed the regulatory role of KDM4D in Toll-Like Receptor (TLR) signaling pathway. Mechanistically, KDM4D catalyzed histone 3 on lysine 9 (H3K9) di-, and tridemethylation, which promoted TLR4 expression, and subsequently prompted liver fibrogenesis by activating NF-κB signaling pathways. KDM4D facilitates TLR4 transcription through demethylation of H3K9, thus activating TLR4/NF-κB signaling pathways in HSCs, contributing to HSC activation and collagen crosslinking, further, hepatic fibrosis progression. Funding: The research was supported by grants from Shanghai New Hundred Talents Program (No: XBR2013091), Shanghai Municipal Commission of Health and Family Planning, Key Developing Disciplines Program (No: 2015ZB0501), Shanghai Key disciplines program of Health and Family Planning (No: 2017ZZ02010) and Shanghai Sailing Program (No: 17YF1405200). Declaration of Interest: Nothing to report. Ethical Approval: Protocols approved by the East China Normal University Care Commission.

Background Tracheostomized patients suffer from communication difficulty, physical pain, swallowing difficulty, and decreased quality of life. In this study, we investigated the current status of communication and swallowing difficulties in tracheostomized patients in Taiwan, and the knowledge of medical personnel about tracheostomized patients and the perceived benefits of referring them to speech therapy. Methods We analyzed both the national data from The Collaboration Center of Health Information Application, and medical insurance data of a medical center in Taipei. We also administered a questionnaire survey to 80 medical personnel before and after an education program was given for patients and medical personnel. Results Treatment referral rates of inpatients with tracheostomy for speech therapy were found to be at 4.87% and 10%, from national and medical center data, respectively, and only a few patients received both communication and swallowing training. Over 50% of the medical personnel never referred any tracheostomized inpatients for speech therapy. The rate of referral was not significantly affected by experience and knowledge of medical personnel of tracheostomy. Conclusion Fundamental education about the availability of speech therapy and speech-language therapists for medical personnel would be the best way to help tracheostomized patients obtain entitled proper speech therapy in Taiwan.

Background & Aims Monoamine oxidase A (MAOA), a catecholamine neurotransmitter degrading enzyme, is closely associated with neurological and psychiatric disorders. However, its role in cancer progression remains unknown. Methods Hepatocellular carcinoma (HCC) tissue arrays (n=254) were used to investigate the correlation between MAOA expression and clinicopathological findings. In vitro invasion and anoikis assays, and in vivo intrahepatic and lung metastasis models were used to determine the role of MAOA in HCC metastasis. Quantitative real-time PCR, western blotting, immunohistochemical staining and HPLC analysis were performed to uncover the mechanism of MAOA in HCC. Results We found that MAOA expression was significantly downregulated in 254 clinical HCC samples and was closely correlated with cancer vasoinvasion, metastasis, and poor prognoses. We then demonstrated that MAOA suppressed norepinephrine/epinephrine (NE/E)-induced HCC invasion and anoikis inhibition, and uncovered that the effects of NE/E on HCC behaviors were primarily mediated through alpha 1A (ADRA1A) and beta 2 adrenergic receptors (ADRB2). In addition to the canonical signaling pathway, which is mediated via adrenergic receptors (ADRs), we found that ADR-mediated EGFR transactivation was also involved in NE-induced HCC invasion and anoikis inhibition. Notably, we found that MAOA could synergize with EGFR inhibitors or ADR antagonists to abrogate NE-induced HCC behaviors. Conclusions Taken together, the results of our study may provide insights into the application of MAOA as a novel predictor of clinical outcomes and indicate that increasing MAOA expression or enzyme activity may be a new approach that can be used for HCC treatment.

A copper-catalyzed asymmetric propargylic amination with a chiral ketimine P,N,N-ligand that proceeds via decarboxylation of propargyl carbamates has been developed. The reaction can be performed under the mild condition for a broad range of substrates, providing the corresponding propargylic amines in high yields and with up to 97% ee. This reaction represents a new and facile access to optically active propargylic amines.

Background & Aims Agents designed to block or alter cytokinesis can kill or stop proliferation of cancer cells. We aimed to identify cytokinesis-related proteins that are overexpressed in hepatocellular carcinoma (HCC) cells and might be targeted to slow liver tumor growth. Methods Using the Oncomine database, we compared the gene expression patterns in 16 cancer microarray datasets and assessed gene enrichment sets using gene ontology. We performed immunohistochemical analysis of an HCC tissue microarray and identified changes in protein levels that are associated with patient survival times. Candidate genes were overexpressed or knocked down with small hairpin RNAs in SMMC7721, MHCC97H, or HCCLM3 cell lines; we analyzed their proliferation, viability, and clone-formation ability and their growth as subcutaneous or orthotopic xenograft tumors in mice. We performed microarray analyses to identify alterations in signaling pathways and immunoblot and immunofluorescence assays to detect and localize proteins in tissues. Yeast 2-hybrid screens and mass spectrometry combined with co-immunoprecipitation experiments were used to identify binding proteins. Protein interactions were validated with co-immunoprecipitation and proximity ligation assays. Chromatin immunoprecipitation, promoter luciferase activity, and quantitative real-time polymerase chain reaction analyses were used to identify factors that regulate transcription of specific genes. Results The genes that were most frequently overexpressed in different types of cancer cells were involved in cell division processes. We identified 3 cytokinesis-regulatory proteins among the 10 genes most frequently overexpressed by all cancer cell types. Rac GTPase activating protein 1 (RACGAP1) was the cytokinesis-regulatory protein that was most highly overexpressed in multiple cancers. Increased expression of RACGAP1 in tumor tissues was associated with shorter survival times of patients with cancer. Knockdown of RACGAP1 in HCC cells induced cytokinesis failure and cell apoptosis. In microarray analyses, we found knockdown of RACGAP1 in SMMC7721 cells to reduce expression of genes regulated by yes-associated protein (YAP) and WW domain containing transcription regulator 1 (WWTR1 or TAZ). RACGAP1 reduced activation of the Hippo pathway in HCC cells by increasing activity of RhoA and polymerization of filamentous actin. Knockdown of YAP reduced phosphorylation of RACGAP1 and redistribution at the anaphase central spindle. We found transcription of the translocated promoter region, nuclear basket protein (TPR) to be regulated by YAP and coordinately expressed with RACGAP1 to promote proliferation of HCC cells. TPR redistributed upon nuclear envelope breakdown and formed complexes with RACGAP1 during mitosis. Knockdown of TPR in HCC cells reduced phosphorylation of RACGAP1 by aurora kinase B and impaired their redistribution at the central spindle during cytokinesis. STAT3 activated transcription of RACGAP in HCC cells. Conclusions In an analysis of gene expression patterns of multiple tumor types, we found RACGAP1 to be frequently overexpressed, which is associated with shorter survival times of patients. RACGAP1 promotes proliferation of HCC cells by reducing activation of the Hippo and YAP pathways and promoting cytokinesis in coordination with TPR.

New chiral ferrocenyl P,N-ligands with a benzoxazole ring as the N-donor group have been synthesized from 2-aminophenol through a three-step transformation and successfully employed in the Ag-catalyzed asymmetric [3+2] cycloaddition of azomethine ylides with electron-deficient alkenes. High diastereoselectivities, excellent enantioselectivities, and good yields have been achieved for a variety of substrates, demonstrating the potential of these new P,N-ligands in asymmetric catalysis.

Hypertrophic scarring is a common disease affecting millions of people around the world, but there are currently no satisfactory drugs to treat the disease. Exaggerated inflammation and mechanical stress have been shown to be two main mechanisms of excessive fibrotic diseases. Here we found that a benzopyran natural product, xiamenmycin, could significantly attenuate hypertrophic scar formation in a mechanical stretch-induced mouse model. The compound suppressed local inflammation by reducing CD4+ lymphocyte and monocyte/macrophage retention in fibrotic foci and blocked fibroblast adhesion with monocytes. Both in vivo and in vitro studies found that the compound inhibited the mechanical stress-induced profibrotic effects by suppressing proliferation, activation, fibroblast contraction, and inactivating FAK, p38, and Rho guanosine triphosphatase signaling. Taken together, the compound could simultaneously suppress both the inflammatory and mechanical stress responses, which are the two pivotal pathological processes in hypertrophic scar formation, thus suggesting that xiamenmycin can serve as a potential agent for treating hypertrophic scar formation and other excessive fibrotic diseases.

Based on the crack propagation mechanism of elastic-plastic fracture, a finite element analysis was performed upon the effect of compressive loading on fatigue crack tip stress field in LY12M aluminum alloy. By the validation of test data, two actual engineering models and a published double-parameter crack growth model, called Zhang-model, are all suitable in the case of negative stress ratio, and are used to describe the test data in the corresponding coordinate system. By comparing the degrees of linear correlation, R2, of each fitting line, it shows that Zhang-model is a better engineering method for life prediction of fatigue crack growth under negative stress ratio of aluminum alloy, some factors can be obtained from elastic-plastic finite element computation, and it will save a lot of funds in the new materials research.

Objective The aim of this study was to examine the serum oxidative stress in patients with severe mitral regurgitation. Design and methods This study analyzed serum oxidative stress index in patients with severe mitral regurgitation [persistent atrial fibrillation (AF) or sinus rhythm], paroxysmal lone AF patients and healthy subjects. Results The serum oxidative stress index was significantly higher in the mitral regurgitation AF group and sinus group than in the lone AF group and healthy subjects (p

The Rhesus (Rh) blood group is the most polymorphic human blood group system, and it is clinically significant in transfusion medicine. About 15% of Caucasoid people are RhD-negative, whereas in the Asian population, the RhD-negative blood type only occurs in 0.1% to 0.5%. However, approximately 30% of apparently RhD-negative Taiwanese people actually were RhD el . Traditionally, we verify RhD el by a serologically adsorption-elution procedure with polyclonal anti-D. In our recent report, RhC phenotype is highly associated with RhD el , and RHD 1227A is a useful genetic marker for RhD el . For setting up a rapid protocol to detect RhD el in clinical laboratory, a total number of 395 Taiwanese serological RhD-negative blood samples, those with RhC (+) phenotypes as selected by serological tests, were further screened by adsorption/elution tests and RHD 1227A allele by specific sequence primer-polymerase chain reaction (SSP-PCR) for RhD el . Among 395 blood samples collected from RhD-negative subjects, the incidence of RhC (+) was 43% (171/395). One hundred and twenty six of the 171 RhC (+) samples were positive for both adsorption/elution for RhD detection and SSP-PCR assay for RHD 1227A. The sensitivity and specificity were 96.9% and 97.5%, respectively, for RHD 1227A detection as compared with the traditional adsorption/elution test. Our results also indicated that RHD 1227A was highly linked to Ce haplotypes (95.2%). In conclusion, combined RhC (+) phenotyping and RHD 1227A analysis can be a simple and accurate laboratory screening protocol for RhD el detection in RhD-negative population.

Background & Aims Desmoplasia and poor vascularity cause severe metabolic stress in pancreatic ductal adenocarcinomas (PDACs). Serotonin (5-HT) is a neuromodulator with neurotransmitter and neuroendocrine functions that contributes to tumorigenesis. We investigated the role of 5-HT signaling in the growth of pancreatic tumors. Methods We measured the levels of proteins that regulate 5-HT synthesis, packaging, and degradation in pancreata from Kras G12D/+ /Trp53 R172H/+ /Pdx1-Cre (KPC) mice, which develop pancreatic tumors, as well as in PDAC cell lines and a tissue microarray containing 81 human PDAC samples. We also analyzed expression levels of proteins involved in 5-HT synthesis and degradation by immunohistochemical analysis of a tissue microarray containing 311 PDAC specimens, and associated expression levels with patient survival times. 5-HT level in 14 matched PDAC tumor and non-tumor tissues were analyzed by ELISA. PDAC cell lines were incubated with 5-HT and cell survival and apoptosis were measured. We analyzed expression of the 5-HT receptor HTR2B in PDAC cells and effects of receptor agonists and antagonists, as well as HTR2B knockdown with small hairpin RNAs. We determined the effects of 5-HT stimulation on gene expression profiles of BxPC-3 cells. Regulation of glycolysis by 5-HT signaling via HTR2B was assessed by immunofluorescence and immunoprecipitation analyses, as well as by determination of the extracellular acid ratio, glucose consumption, and lactate production. Primary PDACs, with or without exposure to SB204741 (a selective antagonist of HTR2B), were grown as xenograft tumors in mice, and SB204741 was administered to tumor-bearing KPC mice; tumor growth and metabolism were measured by imaging analyses. Results In immunohistochemical analysis of a tissue microarray of PDAC specimens, increased levels of TPH1 and decreased level of MAOA, which regulate 5-HT synthesis and degradation, correlated with stage and size of PDACs and shorter patient survival time. We found levels of 5-HT to be increased in human PDAC tissues compared with non-tumor pancreatic tissues, and PDAC cell lines compared with non-transformed pancreatic cells. Incubation of PDAC cell lines with 5-HT increased proliferation and prevented apoptosis. Agonists of HTR2B, but not other 5-HT receptors, promoted proliferation and prevented apoptosis of PDAC cells. Knockdown of HTR2B in PDAC cells, or incubation of cells with HTR2B inhibitors, reduced their growth as xenograft tumors in mice. We observed a correlation between 5-HT and glycolytic flux in PDAC cells; levels of metabolic enzymes involved in glycolysis, the phosphate pentose pathway, and hexosamine biosynthesis pathway increased significantly in PDAC cells following 5-HT stimulation. 5-HT stimulation led to formation of the HTR2B–LYN–p85 complex, which increased PI3K–Akt–mTOR signaling and the Warburg effect by increasing protein levels of MYC and HIF1A. Administration of SB204741 to KPC mice slowed growth and metabolism of established pancreatic tumors and prolonged survival of the mice. Conclusions Human PDACs have increased levels of 5-HT, and PDAC cells increase expression of its receptor, HTR2B. These increases allow for tumor glycolysis under metabolic stress and promote growth of pancreatic tumors and PDAC xenograft tumors in mice.

Monoclonal antibodies (mABs) have been raised against oocyte nuclear proteins of Xenopus laevis and X. borealis and have been screened for species specificity. Although about 40% of all germinal vesicle polypeptides differ between the two species as judged by two-dimensional gel analysis, most mABs react with polypeptides of both species. Biochemical analysis of the antigens by immunoblotting revealed that a homologue of each antigen of one species could be detected in the other species, despite frequent differences in molecular structure. Nevertheless, five strictly species-specific mABs have been identified. All five are directed against the same acidic polypeptide B3 of X. borealis, which is a structurally altered homologue of the protein N1, previously described in X. laevis germinal vesicles. In oocyte nuclei of hybrids between X. laevis females and X. borealis males, polypeptide of both species appear to be accummulated equivalently. Exceptions to this rule are most easily explained by differences between individuals and by the loss of certain alleles resulting from the cross.