Publications by authors named "Yuhui Zhang"

204 Publications

Pericardial Toxicities Associated With Immune Checkpoint Inhibitors: A Pharmacovigilance Analysis of the FDA Adverse Event Reporting System (FAERS) Database.

Front Pharmacol 2021 2;12:663088. Epub 2021 Jul 2.

Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.

Immune checkpoint inhibitors (ICIs) have significantly improved clinical outcomes for a wide range of cancers but can also lead to serious or fatal immune-related adverse events (irAEs). Although ICI-related pericardial toxicities have been reported, the clinical features are not well characterized in real-world studies. To characterize the main features of ICI-related pericardial toxicities and identify factors associated with death. Data from January 1, 2011 to March 31, 2020 in the FDA Adverse Event Reporting System database were retrieved for disproportionality analysis. We used the reporting odds ratio and the information component (IC) to evaluate the association between ICIs and pericardial adverse events. Clinical characteristics of patients with ICI-associated pericardial toxicities were collected and compared between fatal and non-fatal groups. The time to onset following different ICI regimens was further investigated. We identified a total of 705 ICI-associated pericardial toxicities which appeared to influence more men (53.90%) than women (36.03%), with a median age of 63 (interquartile range [IQR] 54-69) years. Patients with lung cancer accounted for the largest proportion (55.6%). ICI therapies were detected with pharmacovigilance signals of pericardial toxicities, corresponding to IC = 2.11 and ROR 4.87 [4.51-5.25]. Nevertheless, there was a lack of association between anti-CTLA-4 and pericardial toxicities. There was no difference in onset time among all ICI regimens. However, TTO of fatal cases (25 days (interquartile range [IQR] 6-70)) occurred statistically earlier than non-fatal cases (42 days (IQR 12-114), = 0.003). ICI monotherapy (PD-1/PD-L1 therapy) and combination therapy can lead to pericardial toxicities that can result in serious outcomes and tend to occur early. Early recognition and management of ICI-related pericardial disorders should attract clinical attention. The findings require further clinical surveillance for the quantification.
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http://dx.doi.org/10.3389/fphar.2021.663088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283181PMC
July 2021

The emerging landscape of peptide-based inhibitors of PCSK9.

Atherosclerosis 2021 Jun 26;330:52-60. Epub 2021 Jun 26.

Institute for Molecular Bioscience, Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science, The University of Queensland, Brisbane, Qld, 4072, Australia. Electronic address:

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a clinically validated target for treating cardiovascular disease (CVD) due to its involvement in cholesterol metabolism. Although approved monoclonal antibodies (alirocumab and evolocumab) that inhibit PCSK9 function are very effective in lowering cholesterol, their limitations, including high treatment costs, have so far prohibited widespread use. Accordingly, there is great interest in alternative drug modalities to antibodies. Like antibodies, peptides are valuable therapeutics due to their high target potency and specificity. Furthermore, being smaller than antibodies means they have access to more drug administration options, are less likely to induce adverse immunogenic responses, and are better suited to affordable production. This review surveys the current peptide-based landscape aimed towards PCSK9 inhibition, covering pre-clinical to patented drug candidates and comparing them to current cholesterol lowering therapeutics. Classes of peptides reported to be inhibitors include nature-inspired disulfide-rich peptides, combinatorially derived cyclic peptides, and peptidomimetics. Their functional activities have been validated in biophysical and cellular assays, and in some cases pre-clinical mouse models. Recent efforts report peptides with potent sub-nanomolar binding affinities to PCSK9, which highlights their potential to achieve antibody-like potency. Studies are beginning to address pharmacokinetic properties of PCSK9-targeting peptides in more detail. We conclude by highlighting opportunities to investigate their biological effects in pre-clinical models of cardiovascular disease. The anticipation concerning the PCSK9-targeting peptide landscape is accelerating and it seems likely that a peptide-based therapeutic for treating PCSK9-mediated hypercholesterolemia may be clinically available in the near future.
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http://dx.doi.org/10.1016/j.atherosclerosis.2021.06.903DOI Listing
June 2021

Combined use of low T3 syndrome and NT-proBNP as predictors for death in patients with acute decompensated heart failure.

BMC Endocr Disord 2021 Jul 2;21(1):140. Epub 2021 Jul 2.

Heart Failure Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, 167 Beilishi Road, 100037, Beijing, China.

Background: In patients with established HF, low triiodothyronine syndrome (LT3S) is commonly present, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a useful marker for predicting death. This study was aimed to evaluate the prognostic value of LT3S in combination with NT-proBNP for risk of death in patients with heart failure (HF).

Methods: A total of 594 euthyroid patients hospitalized with acute decompensated HF were enrolled by design. Of these patients, 27 patients died during hospitalization and 100 deaths were identified in patients discharged alive during one year follow-up. Patients were divided into 2 groups on the base of the reference ranges of free T3 (FT3) levels: LT3S group (FT3 < 2.3pg/mL, n = 168) and non-LT3S group (FT3 ≥ 2.3pg/mL, n = 426).

Results: In multivariable Cox regression, LT3S was significantly associated with 1 year all-cause mortality (adjusted hazard ratio, 1.85; 95 % confidence interval [CI], 1.21 to 2.82; P = 0.005), but not significant for in-hospital mortality (adjusted hazard ratio, 1.58; 95 % CI, 1.58 to 2.82; P = 0.290) after adjustment for clinical variables and NT-proBNP. Addition of LT3S and NT-proBNP to the prediction model with clinical variables significantly improved the C statistic for predicting 1 year all-cause mortality.

Conclusions: In patients with acute decompensated HF, the combination of LT3S and NT-proBNP improved prediction for 1 year all-cause mortality beyond established risk factors, but was not strong enough for in-hospital mortality.
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http://dx.doi.org/10.1186/s12902-021-00801-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252209PMC
July 2021

Quantitative analysis of nine isoflavones in traditional Chinese medicines using mixed micellar liquid chromatography containing sodium dodecylsulfate/β-cyclodextrin supramolecular amphiphiles.

J Sep Sci 2021 Jul 1. Epub 2021 Jul 1.

Institute of Pharmaceutical Analysis, School of Pharmacy, Lanzhou University, Lanzhou, P. R. China.

Isoflavone is one of the phytoestrogens that have estrogenic effects, so it is usually served as an active ingredient for quality control of traditional Chinese medicines rich in isoflavones. Nine isoflavones commonly found in traditional Chinese medicines were separated in 30 min using mixed micellar liquid chromatography. The mobile phase consisted of 0.08 M sodium dodecylsulfate and 6.05 mM β-cyclodextrin:methanol (87:13, v/v) at pH 3 and eluted isocratically at 1 mL/min through a C18 column. In this study, we systematically optimized the chromatographic conditions including the pH, the composition and concentration of surfactants, the type and ratio of organic solvents, and column temperature. The method was validated according to the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use guidelines. There is no report using micellar liquid chromatography to detect isoflavones, and the optimized method has been successfully applied to quantify isoflavones in red clover and Radix Puerariae. This method is efficient, cheap, and convenient. Finally, we verified the existence of supramolecular amphiphilic vesicles in the mobile phase by transmission electron microscopy to explain the increased chromatographic efficiency.
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http://dx.doi.org/10.1002/jssc.202100099DOI Listing
July 2021

Reducing hyperactivated BAP1 attenuates mutant ASXL1-driven myeloid malignancies in human haematopoietic cells.

Cancer Lett 2021 Jun 26;519:78-90. Epub 2021 Jun 26.

State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China. Electronic address:

Additional sex combs-like 1 (ASXL1) is frequently mutated in a variety of myeloid malignancies, resulting in expression of a C-terminal-truncated ASXL1 protein that confers gain of function on the ASXL1-BAP1 deubiquitinase (DUB) complex. Several studies have reported that hyperactivity of BRCA-1-associated protein 1 (BAP1) in deubiquitinating mono-ubiquitinated histone H2AK119 is one of the critical molecular mechanisms in ASXL1 mutation-driven myeloid malignancies in mice. In this study, we found that human haematopoietic stem and progenitor cells (HSPCs) overexpressing truncated ASXL1 (ASXL1) developed an MDS-like phenotype similar to that induced by overexpression of BAP1. We then used shRNAs targeting BAP1 in ASXL1-overexpressing HSPCs and primary leukaemia cells with ASXL1 mutation, demonstrating that reduced BAP1 expression can partially rescue the pathological consequences. RNA sequencing and chromatin immunoprecipitation coupled with quantitative PCR analyses revealed that reduced BAP1 expression suppressed upregulation of the transcription factors AP-1 and EGR1/2, as well as myeloid dysplasia-associated genes, by retarding H2AK119Ub removal caused by ASXL1 mutation. This study indicates that targeting the hyperactive ASXL1-BAP1 DUB complex can attenuate mutant ASXL1-driven myeloid malignancies in human.
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http://dx.doi.org/10.1016/j.canlet.2021.06.019DOI Listing
June 2021

Congestive Heart Failure Exhibited Higher BMI With Lower Energy Intake and Lower Physical Activity Level: Data From the National Health and Examination Nutrition Survey.

Front Cardiovasc Med 2021 9;8:680371. Epub 2021 Jun 9.

State Key Laboratory of Cardiovascular Disease, Heart Failure Center, National Center for Cardiovascular Disease, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Despite that nutritional deficiency existed in congestive heart failure (CHF), there is a large amount of CHF patients suffering from obesity. This study aimed to identify the differences for increased BMI or obesity in CHF patients. This cross-sectional study included adults from the National Health and Nutrition Examination Survey 2007-2016. Differences were compared between CHF participants vs. non-CHF participants, and BMI ≥ 30 kg/m vs. BMI < 30 kg/m CHF participants. CHF participants were with higher BMI, lower energy and macronutrient intake, lower physical activity level and longer rest time, and lower hematocrit and hemoglobin level (all < 0.05) than non-CHF participants. The prevalence of BMI ≥ 30 kg/m in participants with CHF was 53.48%. There was no significant difference observed in energy and macronutrient intake between CHF participants with BMI ≥ 30 kg/m or <30 kg/m. The water intake ( = 0.032), sedentary time ( = 0.002), and hematocrit ( = 0.028) were significantly different between CHF with BMI ≥ 30 kg/m and with <30 kg/m. Compared with non-CHF participants, CHF participants exhibited higher BMI with lower energy and macronutrient intake, lower physical activity level, longer rest time, and hemodilution with lower hematocrit and hemoglobin level. Among CHF participants with BMI ≥ 30 kg/m, higher sedentary time and hematocrit were observed.
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http://dx.doi.org/10.3389/fcvm.2021.680371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221290PMC
June 2021

Biomedical and clinical English model packages for the Stanza Python NLP library.

J Am Med Inform Assoc 2021 Jun 22. Epub 2021 Jun 22.

Department of Radiology, Stanford University, Stanford, California, USA.

Objective: The study sought to develop and evaluate neural natural language processing (NLP) packages for the syntactic analysis and named entity recognition of biomedical and clinical English text.

Materials And Methods: We implement and train biomedical and clinical English NLP pipelines by extending the widely used Stanza library originally designed for general NLP tasks. Our models are trained with a mix of public datasets such as the CRAFT treebank as well as with a private corpus of radiology reports annotated with 5 radiology-domain entities. The resulting pipelines are fully based on neural networks, and are able to perform tokenization, part-of-speech tagging, lemmatization, dependency parsing, and named entity recognition for both biomedical and clinical text. We compare our systems against popular open-source NLP libraries such as CoreNLP and scispaCy, state-of-the-art models such as the BioBERT models, and winning systems from the BioNLP CRAFT shared task.

Results: For syntactic analysis, our systems achieve much better performance compared with the released scispaCy models and CoreNLP models retrained on the same treebanks, and are on par with the winning system from the CRAFT shared task. For NER, our systems substantially outperform scispaCy, and are better or on par with the state-of-the-art performance from BioBERT, while being much more computationally efficient.

Conclusions: We introduce biomedical and clinical NLP packages built for the Stanza library. These packages offer performance that is similar to the state of the art, and are also optimized for ease of use. To facilitate research, we make all our models publicly available. We also provide an online demonstration (http://stanza.run/bio).
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http://dx.doi.org/10.1093/jamia/ocab090DOI Listing
June 2021

Influence of octylphenol on gene expression of gonadotropins and their receptors, testicular structure and mating behavior of male Rana chensinensis.

Environ Toxicol Pharmacol 2021 Jun 18;87:103694. Epub 2021 Jun 18.

College of Life Science, Shaanxi Normal University, Xi'an, 710119, China. Electronic address:

In the present study, responses of the Chinese brown frog (Rana chensinensis) to exposure to different doses and duration of Octyphenol (OP) which degraded from alkylphenol ethoxylates (APEs) were characterized during the adult periods. The effects of OP on growth, development and reproduction and the expression of genes in gonad were investigated. The expression levels of fshβ, lhβ, fshr and lhr had significant differences as the exposure time increased. The pathological and morphological changes were also observed in the OP treatments. Furthermore, the number of TUNEL positive cells and the TUNEL index was elevated after exposed to OP. Besides that, OP treatment could influence its mating behavior and reduce the fertilization rates. Taken together, these results indicated that OP disrupt sex steroid signaling, normal development of spermatogenesis, courtship behavior of male frogs and decline fertilization rate in R. chensinensis.
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http://dx.doi.org/10.1016/j.etap.2021.103694DOI Listing
June 2021

Thromboembolic events associated with immune checkpoint inhibitors: A real-world study of data from the food and drug administration adverse event reporting system (FAERS) database.

Int Immunopharmacol 2021 Jun 12;98:107818. Epub 2021 Jun 12.

Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing Institute of Respiratory Medicine, Beijing 100020, China. Electronic address:

Background: Although there have been a few studies reporting thromboembolic events (TEEs) in patients treated with immune checkpoint inhibitors (ICIs), the detailed profile of the TEEs and the prothrombotic effects of ICIs remain mostly unknown.

Methods: Data from January 2004 to December 2019 in the FAERS database were retrieved. We investigated the clinical characteristics of the TEEs and conducted disproportionality analysis by using reporting odds ratios (ROR) to compare ICIs with the full database and other anti-cancer agents.

Results: We identified 1855 reports of TEEs associated with ICIs. Affected patients tended to be male (59.68%) and older than 65 (47.12%). The case-fatality rate of the reported TEEs was high (38%). The median time to onset (TTO) of all cases was 42 (interquartile range [IQR] 15-96) days and the median TTO of fatal cases (31 [IQR 13-73] days) was significantly shorter than non-fatal cases (50 [IQR 20-108] days, p = 0.000002). ICIs showed increased risks of VTE (ROR 2.81, 95% CI 2.69-2.95) and ATE (ROR 1.44, 95% CI 1.37-1.52) compared with the full database. Compared with protein kinase inhibitors, ICIs showed an increased risk of VTE (ROR 1.23, 95% CI 1.17-1.29), but only anti-PD-L1 showed an increased risk of cerebral ATE (ROR 1.38, 95% CI 1.08-1.76). Compared with chemotherapy, ICIs showed an increased risk of PE (ROR 1.14, 95% CI 1.07-1.21).

Conclusions: Our study suggested ICIs tend to increase risks of VTE and ATE. The poor clinical outcome and early onset of these events should attract clinical attention.
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http://dx.doi.org/10.1016/j.intimp.2021.107818DOI Listing
June 2021

Risk of osteoporosis in patients with erectile dysfunction: A PRISMA-compliant systematic review and meta-analysis.

Medicine (Baltimore) 2021 Jun;100(24):e26326

Department of Urology, The First Affiliated Hospital of Soochow University.

Background: Erectile dysfunction (ED) and osteoporosis are both common health problems and have similar risk factors. Recent studies have found that people with ED have a higher risk of osteoporosis.We aimed to systematically assess osteoporosis risk in patients with ED.

Methods: A systematically research was carried out in Medline via PubMed, Cochrane Library, EMBASE, and Web of Science up to June 4, 2020, to identify articles related to ED and osteoporosis. The 2 researchers independently reviewed the literature, extracted the data, and evaluated the quality of the literature. All analyses were done using RevMan5.3 and Stata14.

Results: A total of 4 studies involving 22,312 participants were included. The meta-analysis results showed that the risk of osteoporosis in the ED group was significantly higher than that in the non-ED group [odds ratio (OR) = 2.66, 95% confidence interval (95% CI) 1.42 to 4.98, P = .002, I2 = 68%]. Interestingly, compared with older participants, the increased risk of osteoporosis in ED patients seemed to be more pronounced in younger participants. Despite the lack of data for meta-analysis, more than half of the literature mentioned this tendency. We found the source of heterogeneity through sensitivity analysis, and there was no significant effect on the results before and after the removal of this literature, indicating that our results were robust. No obvious publication bias was found through Egger method (P = .672).

Conclusion: People with ED have a higher risk of osteoporosis, especially among younger males. Because the assessment of osteoporosis is economical and noninvasive, ED patients should be evaluated by bone mineral density or men with osteoporosis should be further assessed for erectile function.
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http://dx.doi.org/10.1097/MD.0000000000026326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213329PMC
June 2021

Urinary exosomes-based Engineered Nanovectors for Homologously Targeted Chemo-Chemodynamic Prostate Cancer Therapy via abrogating EGFR/AKT/NF-kB/IkB signaling.

Biomaterials 2021 Jun 4;275:120946. Epub 2021 Jun 4.

School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, PR China; Institute of Nano Biomedicine and Engineering, Shanghai Engineering Research Centre for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan RD, Shanghai, 200240, PR China. Electronic address:

Multi-functional nanovectors based on exosomes from cancer cell culture supernatants in vitro has been successfully utilized for tumor-specific targeting and immune escape. However, the labor-intensive purification procedures for rich-dose and high-purity homogeneous exosomes without using targeting ligands are still a challenging task. Herein, we developed a nanovector Exo-PMA/[email protected] through cloaked by urinary exosome membrane as a chemo/chemodynamic theranostic nano-platform for targeted homologous prostate cancer therapy which pertain to the abrogation of Epidermal Growth Factor Receptor (EGFR) and its downstream AKT/NF-kB/IkB signaling instead of ERK signaling cascades. Urinary exosomes-based nanovectors own the same urological cancer cell membrane antigen inclusive of E-cadherin, CD 47 and are free from intracellular substance such as Histone 3 and COX Ⅳ. The targeting properties of the homologous cancer cell are well preserved in Exo-PMA/[email protected] nanovectors in high purity. Meanwhile, the nanovectors based on urinary exosomes from prostate patients deeply penetrated into prostate cancer DU145 3D MCTS, and successfully achieve superior synergistic low-dose chemo/chemodynamic performance in vivo. In addition, the blockage of bypassing EGFR/AKT/NF-kB/IkB signaling pathway is greatly enhanced via elevated intracellular PMA/[email protected] nanoparticles (NPs). It is expected that the rich source and high purity of urinary exosomes offer a reliable solution for mass production of such nanovectors in the future. The targeted homologous cancer therapy based on the urinary exosomes from cancer patients exemplifies a novel targeted anticancer scheme with efficient and facile method.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120946DOI Listing
June 2021

Safety and immunogenicity of a quadrivalent inactivated subunit non-adjuvanted influenza vaccine: A randomized, double-blind, active-controlled phase 1 clinical trial.

Vaccine 2021 06 1;39(29):3871-3878. Epub 2021 Jun 1.

Department of Research and Development, Ab&B Biotech Co., Ltd, Taizhou, Jiangsu, China; Department of Research and Development, Yither Biotech Co., Ltd, Shanghai, China. Electronic address:

Quadrivalent influenza inactivated vaccine (IIV4) is more likely to provide wider protection against yearly circulating influenza viruses than trivalent inactivated influenza vaccine (IIV3). In this study, a total of 320 participants were allocated to four age cohorts (6-35 months, 3-8 years, 9-17 years, and ≥ 18 years; 80 participants/cohort) according to their actual date of birth. Participants in each cohort were randomly assigned to two groups to receive intramuscular injection of the trial vaccine or the comparative vaccine in a one-dose (3-8 years, 9-17 years,and ≥ 18 years) schedule on day 0 or two-dose (6-35 months cohort) schedule on day 0 and 28. The first objective is to evaluate the safety and immunogenicity of the full-dose subunit non-adjuvanted IIV4 (FD-subunit NAIIV4) we developed versus an active-control, China-licensed split-virion NAIIV4, in people ≥ 3 years. The second objective is to evaluate the safety and immunogenicity of FD-subunit NAIIV4 versus the half-dose (HD-subunit NAIIV4) in toddlers aged 6-35 months. Results showed that all adverse reactions noted were rare, mild, and self-limited. In ≥ 3 years cohorts, systemic adverse reactions in FD-subunit NAIIV4 groups were less than the active control split-virion NAIIV4 groups ([Systemic adverse reaction rates (95%CI)], 15.0 (8.6-21.4) versus 19.2(12.1-26.2), p = 0.391). The overall seroprotection efficacy after vaccination were comparable between FD-subunit NAIIV4 and the active control split-virion NAIIV4([Seroprotection rates (95%CI)], H1N1, 99.2(81.3-100.0) versus 94.9(90.9-98.9), p = 0.117; H3N2, 81.7(74.7-88.6) versus 82.1(75.1-89.0), p = 0.939; BV, 75.8(68.2-83.5) versus 74.4(66.4-82.3), p = 0.793; BY, 94.2(90.0-98.4) versus 92.3(87.5-97.1), p = 0.568). Additionally, FD-subunit NAIIV4 has comparable safety and better seroprotection versus that of the half-dose in 6-35 months toddlers groups ([Total adverse reaction rates (95%CI)], 37.5(18.5-56.5) versus 47.5(26.1-68.9), p = 0.366) ([Seroprotection rates (95%CI)], H1N1, 85(56.4-100.0) versus 75.7(47.6-100.0), p = 0.117; H3N2, 50(28.1-71.9) versus 29.7(12.2-47.3), p = 0.070; BV, 75(48.2-100.0) versus 29.7(12.2-47.3), p < 0.001; BY, 75(48.2-100.0) versus 56.8(32.5-81.0), p = 0.091). As a result, the FD-subunit NAIIV4 we developed is safe and effective to provide broader and adequate protection against the circulating influenza viruses during 2018-2019, which could be an essential component of the global preventive strategy for influenza pandemic.
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http://dx.doi.org/10.1016/j.vaccine.2021.05.070DOI Listing
June 2021

Association of Venous Thromboembolism and Early Mortality in Patients with Newly Diagnosed Metastatic Non-Small Cell Lung Cancer.

Cancer Manag Res 2021 18;13:4031-4040. Epub 2021 May 18.

Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing Institute of Respiratory Medicine, Beijing, People's Republic of China.

Purpose: To explore the relationship between venous thromboembolism (VTE) and early mortality (within six months) in Chinese patients with newly diagnosed metastatic non-small cell lung cancer (NSCLC) after entering the era of precision treatment.

Methods: A cohort of 706 consecutive subjects with newly diagnosed metastatic NSCLC were prospectively observed. Clinical and survival data were recorded over a six-month follow-up period. The predictive factors for the occurrence of VTE and the relationship with early mortality were evaluated through univariate and multivariate analyses.

Results: During the six-month follow-up period, VTE events occurred in 12.2% (86/706) of the enrolled patients. In the multivariate analyses for VTE, an age older than 70 years (vs < 70: sub-distribution hazard radio [SHR], 1.678; 95% confidence interval (CI), 1.073-2.600; =0.022), an Eastern Cooperative Oncology Group performance status ≥2 (vs 0/1: SHR, 1.946; 95% CI, 1.277-2.970; =0.002), and having an rearrangement (vs non-rearrangement: SHR, 2.377; 95% CI, 1.186-4.760; =0.015) were significantly associated with the occurrence of VTE. Within six months, 116 subjects (16.4%) died, and the occurrence of VTE (vs no VTE: adjusted HR: 1.863; 95% CI: 1.178-2.947, =0.008) was remarkably associated with early mortality. Further analysis showed 98 patients (13.9%) with early mortality had / wild-type genes, with a risk of early mortality 5.935-fold higher than that of patients with an mutation/ rearrangement. Finally, subgroup analyses showed that VTE occurrence was a significant factor for predicting early mortality in patients with / wild-type genes (adjusted HR: 1.682; 95% CI: 1.023-2.768, =0.041).

Conclusion: Patients with an mutation/ rearrangement had a significantly decreased risk of early mortality in the era of targeted therapy; however, VTE occurrence remained an important predictor for early mortality in metastatic NSCLC patients, especially in patients with / wild-type genes.
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http://dx.doi.org/10.2147/CMAR.S301088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140886PMC
May 2021

Risk of pneumonitis in cancer patients treated with PARP inhibitors: A meta-analysis of randomized controlled trials and a pharmacovigilance study of the FAERS database.

Gynecol Oncol 2021 May 19. Epub 2021 May 19.

Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing, China. Electronic address:

Objective/background: We aimed to evaluate the risk of PARP inhibitors (PARPis) causing pneumonitis in randomized controlled trials (RCTs) and in the real-world practice.

Methods: First, a systematic review based on meta-analysis was conducted. RCTs with available data reporting pneumonitis events for PARPis were eligible for analysis. Second, we conducted a disproportionality analysis based on data from the FDA Adverse Event Reporting System (FAERS) database to characterize the main features of PARPi-related pneumonitis.

Results: 16 trials with 5771 patients were included in our meta-analysis. Compared with control arms, PARPis showed a significant increase in the risk of pneumonitis events (Peto OR 2.68 [95% CI 1.31-5.47], p = 0.007) with no heterogeneity (I = 0%, χp = 0.70). The incidence of pneumonitis across treatment arms was 0.79% (28/3551). In the FAERS database, we identified 84 cases of PARPi-pneumonitis with a fatality rate of 16% (13/79). The median time to event onset was 81 (interquartile range [IQR] 27-131) days and 87% of the adverse events occurred within 6 months.

Conclusion: PARPis increased the risk of pneumonitis that can result in serious outcomes and tend to occur early. Early recognition and management of PARPi-pneumonitis is of vital importance in clinical practice. The mechanisms and risk factors should be studied further to improve clinical understanding and innovative treatment strategies for these diseases.
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http://dx.doi.org/10.1016/j.ygyno.2021.05.012DOI Listing
May 2021

Elevated urinary albumin concentration predicts worse clinical outcomes in hospitalized acute decompensated heart failure patients.

ESC Heart Fail 2021 May 18. Epub 2021 May 18.

Heart Failure Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Objective: To investigate the prognostic value of elevated urinary albumin concentration (UAC) in hospitalized acute decompensated heart failure (ADHF) patients.

Methods: We measured UAC at baseline in 1818 hospitalized ADHF patients who were admitted to our Heart Failure Center. All patients were followed up for a median period of 937.5 days. The primary endpoint was a composite of all-cause death or heart transplantation (HTx) or left ventricular assist device (LVAD) implantation.

Results: In total, 41.5% of ADHF patients had albuminuria (UAC ≥ 20 mg/L). The median value of UAC was 15.5 mg/L. A total of 679 patients died or underwent HTx/LVAD during follow-up. The median UAC was significantly lower in non-HTx/LVAD survivors (14.3 mg/L) than in those who died or underwent HTx/LVAD (18.0 mg/L, P < 0.001). Compared with patients without albuminuria (reference, n = 1064), those with albuminuria had a 1.47-fold higher risk of all-cause death or HTx/LVAD (95% confidence interval [CI]:1.26-1.71, P < 0.001), with hazard ratios (HRs) of 1.42 (95% CI: 1.21-1.66) and 1.74 (95% CI: 1.33-2.26) in patients with microalbuminuria (20 mg/L ≤ UAC < 200 mg/L, n = 617) and macroalbuminuria (UAC ≥ 200 mg/L, n = 137), respectively (both P < 0.001). After adjustment for significant clinical risk factors, the albuminuria group had a higher risk of primary adverse events than the non-albuminuria group (HR = 1.28, 95% CI: 1.09-1.50, P = 0.003), with HRs of 1.27 [95% CI: 1.07-1.49] and 1.36 [95% CI: 1.01-1.84] in patients with microalbuminuria and macroalbuminuria, respectively (P = 0.006 and P = 0.041). The adjusted risk of primary adverse events also increased with the degree of albuminuria in the test for trend (HR = 1.21, 95% CI: 1.06-1.37, P for trend = 0.004). In the subgroup analysis, albuminuria had a significantly greater prognostic value for patients with left ventricular ejection fraction ≥ 40%, eGFR ≥ 60 mL/min/1.73 m , BUN/creatinine ratio ≥ 20 or NT-proBNP < 2098 pg/mL.

Conclusion: The presence of albuminuria evaluated by UAC predicts adverse clinical outcomes in hospitalized ADHF patients.
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http://dx.doi.org/10.1002/ehf2.13399DOI Listing
May 2021

The ROBINS-I and the NOS had similar reliability but differed in applicability: A random sampling observational studies of systematic reviews/meta-analysis.

J Evid Based Med 2021 May 18;14(2):112-122. Epub 2021 May 18.

Department of Evidence-based Medicine and Clinical Epidemiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Objective: There is a lack of evidence on the usage of the quality assessment tool-the Risk Of Bias In Nonrandomized Studies-of Interventions (ROBINS-I). This article aimed to measure the reliability, criterion validity, and feasibility of the ROBINS-I and the Newcastle-Ottawa Scale (NOS).

Methods: A sample of systematic reviews or meta-analyses of observational studies were selected from Medline (2013-2017) and assessed by two reviewers using ROBINS-I and the NOS. We reported on reliability in terms of the first-order agreement coefficient (AC1) statistic. Correlation coefficient statistic was used to explore the criterion validity of the ROBINS-I. We compared the feasibility of the ROBINS-I and NOS by recording the time to complete an assessment and the instances where assessing was difficult.

Results: Five systematic reviews containing 41 cohort studies were finally included. Interobserver agreement on the individual domain of the ROBINS-I as well as the NOS was substantial with a mean AC1 statistic of 0.67 (95% CI: 0.50-0.83) and 0.73 (95% CI: 0.65-0.81), respectively. The criterion validity of the ROBNS-I was moderate (K = 0.52) against NOS. The time in assessing a single study by ROBINS-I varied from 7 hours initially to 3 hours compared with 30 minutes for the NOS. Both reviewers rated "bias due to departure from the intended interventions" the most time-consuming domain in the ROBINS-I, items in the NOS were equal.

Conclusions: The ROBINS-I and the NOS seem to provide the same reliability but vary in applicability. The over-complicated feature of ROBINS-I may limit its usage and a simplified version is needed.
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http://dx.doi.org/10.1111/jebm.12427DOI Listing
May 2021

Photoluminescence and optical temperature measurement of Mn/Er co-activated double perovskite phosphor through site-advantageous occupation.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Oct 9;259:119797. Epub 2021 Apr 9.

Department of Chemistry, University of Shanghai for Science and Technology, Shanghai 200093, PR China.

Because traditional methods based on thermal coupling energy level temperature measurement have large errors, a new temperature sensing strategy is proposed to attain strong sensitivity and excellent signal resolution ability. The rare-earth and also transition metal ions with poles apart thermal quenching channels are used as dual emission centers to find a suitable host to achieve high-efficiency dual-mode emission. In this work, a string of phosphors with NaLaMgWO (NLMW) as the host, the single-doped and double-doped Mn and Er phosphors were adopted by the traditional high temperature solid-state reaction method. The crystallographic structure of the phosphor was analyzed by X-ray power diffraction and Rietveld refinement methods, and the results showed that a pure double perovskite phosphor with a monoclinic structure was successfully prepared. The photoluminescence excitation and emission spectrum properties, CIE chromaticity coordinates and photoluminescence spectra at different temperatures are detailed studied. Excited by ultraviolet light (300 nm), corresponding to the A→T transition of Mn and the charge transfer from O to W of Er. There is no energy transfer between Mn and Er. NLMW:Mn/Er phosphors were especially sensitive to temperature changes within the scope of 303 K to 523 K. As the temperature increases, the fluorescence intensity of Mn is thermally quenched faster than Er. The luminescent intensity ratio of Er thermal coupling level and the FIR of Er/Mn are used to study the temperature performance. The results show that the maximum relative sensitivity of FIR up to 1.31% K, which is higher than the maximum temperature sensitivity based on the thermal coupling energy level, and which is beyond most of the non-contact temperature measurement materials previously reported, confirming that NLMW:Mn/Er phosphors have application potential in non-contact temperature measurement.
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http://dx.doi.org/10.1016/j.saa.2021.119797DOI Listing
October 2021

Markov Processes and Related Topics (III).

Front Math China 2021 Apr 28:1-2. Epub 2021 Apr 28.

Research Center for Stochastics; School of Mathematical Sciences, Beijing Normal University, Beijing, 100875 China.

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http://dx.doi.org/10.1007/s11464-021-0924-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079852PMC
April 2021

Effect of the interface on femtosecond laser damage of a metal-dielectric low dispersion mirror.

Opt Express 2021 Mar;29(6):8171-8180

Metal-dielectric low dispersion mirrors (MLDM) have a promising application prospect in petawatt (PW) laser systems. We studied the damage characteristics of MLDM and found that the damage source of MLDM (Ag + AlO+SiO) is located at the metal-dielectric interface. We present the effect of the interface on the femtosecond laser damage of MLDM. Finite element analysis shows that thermal stress is distributed at the interface, causing stress damage which is consistent with the damage morphology. After enhancing the interface adhesion and reducing the residual stress, the damage source transfers from the interface to a surface SiO layer, and the damage threshold can be increased from 0.60 J/cm to 0.73 J/cm. This work contributes to the search for new techniques to improve the damage threshold of MLDM used in PW laser systems.
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http://dx.doi.org/10.1364/OE.416141DOI Listing
March 2021

Detection of the chiral drug Ephedrine by resonance Rayleigh scattering based on Ce functionalized gold nanoparticles.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Jul 17;255:119695. Epub 2021 Mar 17.

Chongqing Three Gorges University, Wanzhou, Chongqing 404100, China. Electronic address:

Two chiral drugs, ephedrine (EH) and pseudoephedrine (PEH), were commonly used in clinical treatment. Ephedrine (EH) and pseudoephedrine (PEH) could make different changes in resonance Rayleigh scattering spectrum of the detection system which use Ce functionalized gold nanoparticles as probe. Therefore, a new method of detecting EH and PEH separately was developed. The RRS spectrum and UV-Vis absorption spectrum of AuNPs-Ce detection system was analyzed in order to discuss the mechanism. Under optimal experimental conditions, the linear range of EH and PEH were 20-920 ng/mL and 40-520 ng/mL, respectively. The detection limit were 1.9 ng/mL and 3.8 ng/mL, respectively. Last used for actual testing, this method had obtained good results.
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http://dx.doi.org/10.1016/j.saa.2021.119695DOI Listing
July 2021

Correction to: Long non-coding RNA H19 promotes colorectal cancer metastasis via binding to hnRNPA2B1.

J Exp Clin Cancer Res 2021 Mar 23;40(1):111. Epub 2021 Mar 23.

Center for Digestive Disease, the Seventh Affiliated Hospital of Sun Yat-sen University, 628 Zhenyuan Road, Shenzhen, 518000, Guangdong, China.

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http://dx.doi.org/10.1186/s13046-021-01911-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988987PMC
March 2021

The assessment of psychology, quality of life in acne patients and evaluation of ALA-PDT for moderate to severe acne.

Photodiagnosis Photodyn Ther 2021 Mar 27;33:102099. Epub 2020 Nov 27.

Department of Dermatology, The First Hospital of China Medical University, Shenyang, 110000, China. Electronic address:

Objective: To evaluate the state of psychology and quality of life of patients effected by acne and also the efficacy and safety of photodynamic therapy with topical 5-aminolevulinic acid (ALA-PDT) for moderate to severe acne patients.

Methods: In the questionnaire part, a pre-designed form was filled out. The questionnaire was comprised of 2 sections related to acne including sociodemographic and disease information as well as Cardiff Acne Disability Index (CADI) and Self-Rating Anxiety Scale (SAS). In the trial part, the ALA-PDT was applied to moderate to severe acne patients. Fresh 5% ALA solution was topically applied to face or face & neck. After 1 h's incubation, a LED device was illuminated. A power density of 60-100 mW/cm was delivered for 20 min. All the patients finished 3-4 sessions of ALA-PDT at 7-10 days intervals. Non-invasive detections were taken for skin moisture, oil, and VISIA indexes. Adverse events were recorded during and after the treatment.

Results: A total of 247 acne patients finished questionnaires. Over 97 % patients were assessed as mild to severe impacts in CADI questionnaire and 37.6 % patients had various degrees of anxiety in SAS questionnaire. The higher the BMI was, the higher the CADI points were (G = 0.278, p = 0.005). The severity of acne was correlated with psychology and quality of life (CADI: G = 0.367, p = 0.000; SAS: G = 0.285, p = 0.003). A total of 116 patients with moderate or severe acne accepted ALA-PDT and completed at least 3 sessions (PDT3) or even PDT4. After 1 session of treatment (AT1) and AT2, the efficiencies of all patients were 5.2 % and 29.3 %. For patients with PDT3, the efficiencies at follow-up at 1st month after last session (FU1), FU2 and FU3 were 59.4 %, 66.7 % and 78.3 %, respectively. For patients with PDT4, the efficiencies at AT3 and FU1-3 were 51.3 %, 63.6 %, 76.5 % and 85.7 %, respectively. The efficacies of PDT4 patients showed an increasing trend from FU1 to FU3 (G = 0.480, p = 0.004). Acne lesions of mild to severe were correlated with the treatment efficacies (FU1: G = 0.354, p = 0.000; FU2: G = 0.474, p = 0.000; FU3: G = 0.397, p = 0.000). Nearly 15 % patients were followed up for 12 months and among them 52.9 % patients were able to maintain ≥90 % improvement rate. There were no statistically significant differences before and after treatment (p > 0.05) according to the skin moisture content, oil content, ultraviolet ray spots, brown spots, red areas, and purple textures measured. The adverse reactions of ALA-PDT, including local burning sensation, mild pain sensation, mild edema erythema, reactive acne, pigmentation, etc., were temporary and tolerable.

Conclusion: In our study, 97.2 % patients were rated as impact in CADI questionnaire and 37.6 % patients had anxiety in SAS questionnaire. It is necessary to control weight and disease progression. The efficiencies of ALA-PDT for moderate and severe acne were 59.4%-85.7% at follow-ups of 1st, 2nd or 3rd month after last session. The adverse reactions of ALA-PDT were temporary and tolerable.
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http://dx.doi.org/10.1016/j.pdpdt.2020.102099DOI Listing
March 2021

Combining IL-10 and Oncolytic Adenovirus Demonstrates Enhanced Antitumor Efficacy Through CD8 T Cells.

Front Immunol 2021 26;12:615089. Epub 2021 Feb 26.

Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.

Oncolytic viruses are of growing importance in cancer therapeutics since they combine direct oncolytic effect and the stimulation of antitumor immunity. Emerging evidences showed that the function of oncolytic viruses is dependent on immune response in tumor microenvironment, and the modulation of immunity could influence their efficacy. Here we combined the interleukin 10 (IL-10) and oncolytic adenovirus Ad-hTERT to treat lung cancer and explored the underlying mechanism under combination therapy. Lewis lung carcinoma (LLC) and B16F10 tumor-bearing immunocompetent C57BL/6 mice that received Ad-hTERT or IL-10 alone showed mild antitumor effect, while the combination therapy shrink tumor bulks and prolonged survival remarkably. In addition, IL-10 didn't show direct influence on tumor cell viability or Ad-hTERT mediated tumor cell lysis . To further explore the influence of combination therapy mediated antitumor capacity, we eliminated CD8 T, CD4 T or natural killer (NK) cells in LLC and B16F10-bearing C57BL/6 mice, and found that CD8 T cells were critical mediator in the combination therapy. The combination therapy induced intensive infiltration of CD8 T cells in tumors, increased tumor-specific IFN-γ secretion by CD8 T cells. The long-term tumor-specific immune memory induced by the combination therapy rejected rechallenge by respective tumor cell lines. This study demonstrated that the therapy combining IL-10 and Ad-hTERT augmented antitumor efficacy which was CD8 T cells dependent. Our findings paved the way to combine cytokines and oncolytic viruses to enhance antitumor immunotherapy in treating cancer.
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http://dx.doi.org/10.3389/fimmu.2021.615089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952747PMC
July 2021

Myocardial ischemia-reperfusion induced cardiac extracellular vesicles harbour proinflammatory features and aggravate heart injury.

J Extracell Vesicles 2021 Feb 23;10(4):e12072. Epub 2021 Feb 23.

Research Center for Translational Medicine Shanghai East Hospital Tongji University School of Medicine Shanghai P.R. China.

Extracellular vesicles (EVs) curb important biological functions. We previously disclosed that ischemia-reperfusion (IR) induces increased release of EVs (IR-EVs) in the heart. However, the role of IR-EVs in IR pathological process remains poorly understood. Here we found that adoptive transfer of IR-EVs aggravated IR induced heart injury, and EV inhibition by GW4869 reduced the IR injury. Our in vivo and in vitro investigations substantiated that IR-EVs facilitated M1-like polarization of macrophages with increased expression of proinflammatory cytokines. Further, we disclosed the miRNA profile in cardiac EVs and confirmed the enrichment of miRNAs, such as miR-155-5p in IR-EVs compared to EVs from the sham heart (S-EVs). In particular, IR-EVs transferred miR-155-5p to macrophages and enhanced the inflammatory response through activating JAK2/STAT1 pathway. Interestingly, IR-EVs not only boosted the local inflammation in the heart, but even triggered systemic inflammation in distant organs. Taken together, we newly identify an IR-EVs-miR-155-5pM1 polarization axis in the heart post IR. The EVs derived from IR-injured heart contribute to both local and systemic inflammation. Importantly, EV inhibition by GW4869 is supposed to be a promising therapeutic strategy for IR injury.
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http://dx.doi.org/10.1002/jev2.12072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902529PMC
February 2021

Harnessing Ionic Power from Equilibrium Electrolyte Solution via Photoinduced Active Ion Transport through van-der-Waals-Like Heterostructures.

Adv Mater 2021 Apr 3;33(14):e2007529. Epub 2021 Mar 3.

CAS Key Laboratory of Bio-Inspired Materials and Interfacial Science, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, 100190, P. R. China.

Nanofluidic ion transport through van der Waals heterostructures, composed of two or more types of reconstructed 2D nanomaterials, gives rise to fascinating opportunities for light-energy harvesting, due to coupling between the optoelectronic properties of the layered constituents and ion transport in between the atomic layers. Here, a photoinduced active ion transport phenomenon through transition metal dichalcogenides (TMDs)-based van-der-Waals-like multilayer heterostructures is reported for harnessing ionic power from equilibrium electrolyte solution. The binary heterostructure comprises sequentially stacked 2D-WS and 2D-MoS multilayers with sub-1 nm interlayer spacing. Upon visible-light illumination, a net ionic flow is initiated through the Janus membrane, suggesting a directional cationic transport from WS to MoS part. The transport mechanism is explained in terms of a photovoltaic effect due to type II band alignment of WS /MoS heterostructures. The driving mechanism can be generally applied to a variety of heterogeneous TMD membranes with type II semiconductor heterojunctions. In equilibrium ionic solutions, the maximum ionic photoresponse approaches ≈21 µA cm and ≈45 mV under one sun equivalent excitation. Under optimized conditions, the harvested power density reaches 2 mW m . The proof-of-concept demonstration of photonic-to-ionic power generation within angstrom-scale confinement anticipates potential for light-controlled ionic circuits, artificial photosynthesis, and biomimetic energy conversion.
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http://dx.doi.org/10.1002/adma.202007529DOI Listing
April 2021

Basal Rachis Internode Injection (BRII): A novel inoculation method to evaluate wheat resistance to Fusarium head blight.

Phytopathology 2021 Feb 18. Epub 2021 Feb 18.

Key Laboratory of Plant Functional Genomics of the Ministry of Education/Jiangsu Key Laboratory of Crop Genomics and Molecular Breeding/Collaborative Innovation of Modern Crops and Food Crops in Jiangsu/Jiangsu Key Laboratory of Crop Genetics and Physiology, College of Agriculture, Yangzhou University, Yangzhou 225009, China, Yangzhou, China;

Fusarium head blight (FHB) is one of the most destructive fungal diseases of wheat. Difficulties in reliably phenotyping of this disease, however, greatly hindered the understanding of the mechanism of wheat-pathogen interaction and genetic improvement of FHB resistance. Here we report a novel inoculation method called "Basal Rachis Internode Injection" (BRII), which is implemented by injecting inoculum into the basal internode of a rachis instead of a floret as done in single floret inoculation (SFI). One of the prominent advantages of BRII over SFI and other traditional methods lies in its independence of moisture-maintaining system that is required for all existing methods, thus being insensitive to environmental humidity and cost-effective. Another unique feature for BRII is that this method produces nearly clear-cut reaction types, by which FHB resistance could be treated as a qualitative trait because generally no FHB symptom appeared on the spikelets of resistant genotypes. In addition, BRII outperformed SFI by higher infection rate and better goodness-of-fit with known FHB resistance and QTL components in a panel of 15 genotypes, as well as two populations of recombinant inbred lines (RILs) segregating in Fhb1. To be noteworthy, BRII and SFI methods are not mutually replaceable but rather complimentary to each other since each method has its own advantage in differentiating FHB resistance among genotypes. Combining these two methods would significantly improve the reliability and consistency of FHB phenotyping in wheat.
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http://dx.doi.org/10.1094/PHYTO-11-20-0488-RDOI Listing
February 2021

Laser-induced layers peeling of sputtering coatings at 1064 nm wavelength.

Sci Rep 2021 Feb 12;11(1):3783. Epub 2021 Feb 12.

Laboratory of Thin Film Optics, Key Laboratory of Materials for High Power Laser, Shanghai Institute of Optics and Fine Mechanics, Shanghai, 201800, China.

Large-scale layers peeling after the laser irradiation of dual ion beam sputtering coatings is discovered and a model is established to explain it. The laser damage morphologies relate to the laser fluence, showing thermomechanical coupling failure at low energy and coating layers separation at high energy. High-pressure gradients appear in the interaction between laser and coatings, resulting in large-scale layer separation. A two-step laser damage model including defect-induced damage process and ionized air wave damage process is proposed to explain the two phenomena at different energy. At relatively high energies (higher than 20 J/cm), ionization of the air can be initiated, leading to a peeling off effect. The peeling effect is related to the thermomechanical properties of the coating materials.
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http://dx.doi.org/10.1038/s41598-020-80304-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881021PMC
February 2021

Graphene oxide and Lambda exonuclease assisted screening of L-carnitine aptamers and the site-directed mutagenesis design of C-rich structure aptamer.

Biochem Biophys Res Commun 2021 03 5;545:171-176. Epub 2021 Feb 5.

School of Chemistry and Environmental Engineering, Chongqing Three Gorges University, Chongqing, 404000, China. Electronic address:

In this study, Graphene Oxide (GO) was used to screen the binding with the aptamers of L-carnitine chiral enantiomers. The ssDNA library was prepared by the method of Lambda exonuclease. In addition, a simple casing device was designed to improve the purification and recovery efficiency of the small ssDNA fragments in the process of screening. Finally, more than 160,000 aptamer sequences were obtained by high-throughput sequencing. We determined the strongest affinity aptamer sequence, CA04, by the Resonance Rayleigh scattering (RRS) technology. We also analyzed the key binding sites (in the 16th position case) of the truncated aptamer sequence CAD10. Interestingly, we found that aptamer CA10 and CA06 were both C-rich bases through sequence alignment and analysis, and the aptamer CA10 was confirmed that the CA10 and CA06 were formed under acidic conditions (pH 4.5) by CD spectrum and ESI-MS analysis. The interaction between gold nanoparticles (AuNPs) and functionalized aptamer CA10 was analyzed. We used Site-directed mutagenesis design and QGRS Mapper to optimize aptamer CA10, where an optimal aptamer CA10-03 were obtained after affinity analysis. It is also proved to be an effective method to obtain stronger affinity aptamer. Meanwhile, Native-PAGE and UV spectrum analysis were performed on the mutation sequences, and the interaction with ThT was analyzed. Finally, it is hoped that my study can provide help for later identification and detection of L-carnitine.
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http://dx.doi.org/10.1016/j.bbrc.2021.01.044DOI Listing
March 2021

Financing Adolescent Health in China: How Much, Who Pays, and Where It Goes.

J Adolesc Health 2020 11 24;67(5S):S38-S47. Epub 2020 Nov 24.

Division of Global Health Equity, Brigham & Women's Hospital, Boston, Massachusetts; Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts.

Purpose: Adolescent health has been gaining increasing attention in the Sustainable Development Goals era. Data on adolescent health financing are essential for evidence-based policy planning and evaluation. Little is known on national expenditure on adolescent health in China. To inform decision-making on national strategies of adolescent health and development, this study estimated expenditure on adolescent health-care utilization in China and identified funding sources and their allocation among different health functions.

Methods: We constructed and implemented an institutional survey and collected primary financial data from health institutions in the nine selected administrative provinces in 2014. We used the collected data to generate estimate of proportion of health spending on adolescent health and its breakdowns by health-care functions, health-care financing schemes, and diseases based on primary diagnosis. We applied the proportion estimates to the 2014 national-level health expenditure data and estimated national-level estimates of spending on adolescent health and breakdowns in aforementioned areas.

Results: Spending on adolescents health in 2014 amounted to CNY82.1 billion (USD 13.4 billion) or 2.6% of the total health expenditures in the year. Per adolescent health expenditures was CNY525 (USD 85.5), less than per capita health spending (CNY2349, USD382.4). National spending on adolescent health was 73.1% on curative care and 10.3% on preventive care. Out-of-pocket spending is the major source of adolescent health financing, contributing to 57.9% of total spending on adolescent health. Spending on respiratory, digestive, injury and poisoning, genitourinary diseases, and neoplasms accounted for 59.8% of curative care expenditures on adolescents.

Conclusions: Current financing mechanism on adolescent health stressed on curative care and imposed a large portion of financial burden on households. Future investment on adolescent health shall focus more on preventive care. Financing schemes shall be adjusted so as to reduce household out-of-pocket spending on medical care used by adolescents.
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http://dx.doi.org/10.1016/j.jadohealth.2020.03.033DOI Listing
November 2020

Film levitation and central jet of droplet impact on nanotube surface at superheated conditions.

Phys Rev E 2020 Oct;102(4-1):043108

State Key Laboratory of Mechanical Transmission, School of Materials Science and Engineering, Chongqing University, Chongqing 400044, China.

Influences of surface nanotubes at high temperatures are investigated on droplet impact dynamics and Leidenfrost effect. Five distinct regimes of impact droplets are found on the nanotube surface, including contact boiling, film levitation, central jet levitation, central jet, and Leidenfrost phenomenon. The regimes of film levitation, central jet levitation, and central jet are characterized by either film levitation and/or liquid central jet. The regime of Leidenfrost phenomenon is characterized by droplet bounce-off behavior free of any liquid jets. Film levitation is driven by the vaporization of two parts of the droplet, with one as the droplet bottom layer over the contact area above the nanotube structure, and the other as the hemiwicking liquid in nanotubes. Both the vaporization is impaired by increasing the surface temperature, which is attributed to the reduced contact time and less extent of spread of the droplet at a higher surface temperature. The central jet phenomenon is driven by the vapor stream produced by hemiwicking liquid in the central area upon impact. It is enhanced and then suppressed by elevating the surface temperature, resulting from the collective effects of the vapor pressure in nanotubes which increases with the surface temperature, and the cross-sectional area of the vapor stream, which increases and then decreases with the surface temperature. At a high Weber number, the Leidenfrost temperature can be increased by 125^{∘}C on the nanotube surface, implying a great potential in heat transfer enhancement for droplet-based applications.
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http://dx.doi.org/10.1103/PhysRevE.102.043108DOI Listing
October 2020