Publications by authors named "Caihong Li"

73 Publications

Metabolic response of soybean leaves induced by short-term exposure of ozone.

Ecotoxicol Environ Saf 2021 Apr 11;213:112033. Epub 2021 Feb 11.

State Key Laboratory of Vegetation and Environmental Change, Institute of Botany, the Chinese Academy of Sciences, Beijing, China. Electronic address:

The ever-increasing ozone (O) concentration has led to reduced production and altered quality of soybean. Abundant reports have explored the damage mechanisms of O on soybean. However, how the elevated O affects metabolite profiling of soybean remains to be poorly understood. Here, we compare the metabolic profile of soybean leaves under charcoal filtered air (CF, <20 ppb) and short-term elevated O concentration (EO, 100 ppb). High level of O affects metabolites for the tricarbonic acid (TCA) cycle, reactive oxygen species, cell wall composition and amino acids. Significantly, jasmonic acid-related metabolite promoting stomata closure is highly induced with 125-fold change. Furthermore, O fumigation alters the expression of genes contributing to the biosynthesis of certain metabolites in TCA cycle. Together, these findings identify a wide range of changed metabolites in response to O pollution. Our results pave the way for the genetic improvement of soybean to adapt to O pollution to maintain stable yields.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112033DOI Listing
April 2021

6-month consequences of COVID-19 in patients discharged from hospital: a cohort study.

Lancet 2021 01 8;397(10270):220-232. Epub 2021 Jan 8.

Department of Pulmonary and Critical Care Medicine, National Center for Respiratory Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Beijing, China; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Department of Pulmonary and Critical Care Medicine, Capital Medical University, Beijing, China; Tsinghua University-Peking University Joint Center for Life Sciences, Beijing, China. Electronic address:

Background: The long-term health consequences of COVID-19 remain largely unclear. The aim of this study was to describe the long-term health consequences of patients with COVID-19 who have been discharged from hospital and investigate the associated risk factors, in particular disease severity.

Methods: We did an ambidirectional cohort study of patients with confirmed COVID-19 who had been discharged from Jin Yin-tan Hospital (Wuhan, China) between Jan 7, 2020, and May 29, 2020. Patients who died before follow-up, patients for whom follow-up would be difficult because of psychotic disorders, dementia, or re-admission to hospital, those who were unable to move freely due to concomitant osteoarthropathy or immobile before or after discharge due to diseases such as stroke or pulmonary embolism, those who declined to participate, those who could not be contacted, and those living outside of Wuhan or in nursing or welfare homes were all excluded. All patients were interviewed with a series of questionnaires for evaluation of symptoms and health-related quality of life, underwent physical examinations and a 6-min walking test, and received blood tests. A stratified sampling procedure was used to sample patients according to their highest seven-category scale during their hospital stay as 3, 4, and 5-6, to receive pulmonary function test, high resolution CT of the chest, and ultrasonography. Enrolled patients who had participated in the Lopinavir Trial for Suppression of SARS-CoV-2 in China received severe acute respiratory syndrome coronavirus 2 antibody tests. Multivariable adjusted linear or logistic regression models were used to evaluate the association between disease severity and long-term health consequences.

Findings: In total, 1733 of 2469 discharged patients with COVID-19 were enrolled after 736 were excluded. Patients had a median age of 57·0 (IQR 47·0-65·0) years and 897 (52%) were men. The follow-up study was done from June 16, to Sept 3, 2020, and the median follow-up time after symptom onset was 186·0 (175·0-199·0) days. Fatigue or muscle weakness (63%, 1038 of 1655) and sleep difficulties (26%, 437 of 1655) were the most common symptoms. Anxiety or depression was reported among 23% (367 of 1617) of patients. The proportions of median 6-min walking distance less than the lower limit of the normal range were 24% for those at severity scale 3, 22% for severity scale 4, and 29% for severity scale 5-6. The corresponding proportions of patients with diffusion impairment were 22% for severity scale 3, 29% for scale 4, and 56% for scale 5-6, and median CT scores were 3·0 (IQR 2·0-5·0) for severity scale 3, 4·0 (3·0-5·0) for scale 4, and 5·0 (4·0-6·0) for scale 5-6. After multivariable adjustment, patients showed an odds ratio (OR) 1·61 (95% CI 0·80-3·25) for scale 4 versus scale 3 and 4·60 (1·85-11·48) for scale 5-6 versus scale 3 for diffusion impairment; OR 0·88 (0·66-1·17) for scale 4 versus scale 3 and OR 1·77 (1·05-2·97) for scale 5-6 versus scale 3 for anxiety or depression, and OR 0·74 (0·58-0·96) for scale 4 versus scale 3 and 2·69 (1·46-4·96) for scale 5-6 versus scale 3 for fatigue or muscle weakness. Of 94 patients with blood antibodies tested at follow-up, the seropositivity (96·2% vs 58·5%) and median titres (19·0 vs 10·0) of the neutralising antibodies were significantly lower compared with at the acute phase. 107 of 822 participants without acute kidney injury and with estimated glomerular filtration rate (eGFR) 90 mL/min per 1·73 m or more at acute phase had eGFR less than 90 mL/min per 1·73 m at follow-up.

Interpretation: At 6 months after acute infection, COVID-19 survivors were mainly troubled with fatigue or muscle weakness, sleep difficulties, and anxiety or depression. Patients who were more severely ill during their hospital stay had more severe impaired pulmonary diffusion capacities and abnormal chest imaging manifestations, and are the main target population for intervention of long-term recovery.

Funding: National Natural Science Foundation of China, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, National Key Research and Development Program of China, Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis, and Peking Union Medical College Foundation.
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http://dx.doi.org/10.1016/S0140-6736(20)32656-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833295PMC
January 2021

Butylphthalide enhances recovery from sudden deafness.

Am J Otolaryngol 2021 Mar-Apr;42(2):102891. Epub 2021 Jan 4.

Department of Otolaryngology Head and Neck Surgery, General Hospital of Southern Theater Command of PLA (Guangzhou Liuhuaqiao Hospital), Liuhua road 111, Guangzhou 510010, Guangdong, China.

Objectives: Cochlear microcirculation disturbance caused by vasculopathy is a common cause of sudden deafness (SD). Reactive oxygen species (ROS) plays an important role in cochlear injury during ischemia-reperfusion. Butylphthalide can improve microcirculation, reduce ROS formation and inhibit apoptosis. The aim of this study was to investigate the therapeutic effect of butylphthalide on patients with SD.

Patients And Methods: The hearing gains from 32 ears treated with butylphthalide were compared with that of 32 ears treated with non-butylphthalide. Butylphthalide capsules was administrated orally on an empty stomach for 10 continuous days. There were no significant differences in audiological and clinical data between butylphthalide and non-butylphthalide groups.

Results: The hearing gain of butylphthalide group at 500, 1000, 2000, and 4000 Hz was significantly higher than that of non-butylphthalide group correspondingly (P<0.01). And, the hearing gain at PTA (pure-tone average of 500, 1000, 2000, and 4000 Hz) in butylphthalide group was significantly higher than that of non-butylphthalide group (P<0.01).

Conclusion: The recovery of hearing in butylphthalide group was significantly better than that of non-butylphthalide group. It is confirmed that butylphthalide has a definite therapeutic effect on SD.
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http://dx.doi.org/10.1016/j.amjoto.2020.102891DOI Listing
January 2021

Assessing the effects of elevated ozone on physiology, growth, yield and quality of soybean in the past 40 years: A meta-analysis.

Ecotoxicol Environ Saf 2021 Jan 18;208:111644. Epub 2020 Nov 18.

State Key Laboratory of Vegetation and Environmental Change, Institute of Botany, The Chinese Academy of Sciences, Beijing, China; College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, China. Electronic address:

Soybean (Glycine max) production is seriously threatened by ground-level ozone (O) pollution. The goal of our study is to summarize the impacts of O on physiology, growth, yield, and quality of soybean, as well as root parameters. We performed meta-analysis on the collated 48 peer-reviewed papers published between 1980 and 2019 to quantitatively summarize the response of soybean to elevated O concentrations ([O]). Relative to charcoal-filtered air (CF), elevated [O] significantly accelerated chlorophyll degradation, enhanced foliar injury, and inhibited growth of soybean, evidenced by great reductions in leaf area (-20.8%), biomass of leaves (-13.8%), shoot (-22.8%), and root (-16.9%). Shoot of soybean was more sensitive to O than root in case of biomass. Chronic ozone exposure of about 75.5 ppb posed pronounced decrease in seed yield of soybean (-28.3%). In addition, root environment in pot contributes to higher reduction in shoot biomass and yield of soybean. Negative linear relationships were observed between yield loss and intensity of O treatment, AOT40. The larger loss in seed yield was significantly associated with higher reduction in shoot biomass and other yield component. This meta-analysis demonstrates the effects of elevated O on soybean were pronounced, suggesting that O pollution is still a soaring threat to the productivity of soybean in regions with high ozone levels.
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http://dx.doi.org/10.1016/j.ecoenv.2020.111644DOI Listing
January 2021

A Campus Climate/Violence Survey's Psychometrics and Findings.

Violence Against Women 2020 Nov 19:1077801220969870. Epub 2020 Nov 19.

University of Kentucky, Lexington, USA.

Data from a campus climate/violence survey (CCS) include psychometric information for survey items/scales plus findings from a large state university to promote its usefulness for assessment of interpersonal violence/harassment. This CCS can thus be evaluated for its measurement and documented findings, allowing for benchmarking purposes. An innovative measurement strategy is introduced to comprehensively capture incidence of victimization types through streamlined questioning. Tables provide detailed data for 6,995 undergraduate and graduate/professional students over a 1-year period. Adding to published literature on existing CCSs, this article provides the range of information needed for universities to determine the potential usefulness of a CCS.
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http://dx.doi.org/10.1177/1077801220969870DOI Listing
November 2020

Walnut protein hydrolysates, rich with peptide fragments of WSREEQEREE and ADIYTEEAGR ameliorate UV-induced photoaging through inhibition of the NF-κB/MMP-1 signaling pathway in female rats.

Food Funct 2020 Dec 18;11(12):10601-10616. Epub 2020 Nov 18.

College of Food Science and Technology, Guangdong Ocean University, Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Province 524088, China.

Skin photoaging is a complicated pathological process, and the imbalance of inflammatory regulation is associated highly with photoaging progression. Previously, prepared walnut protein hydrolysates (WPH), rich with peptide fragments of WSREEQEREE and ADIYTEEAGR demonstrated desirable photoprotection. However, it remains unclear if the photoprotection is mediated by the targeted inhibition of the NF-κB signaling pathway. Herein, we examined the regulation of WPH on inflammatory cytokine expression, and elucidated the modulation of the NF-κB/MMP-1 signaling pathway by WPH in a photoaging SD rat model. WPH significantly reduced the expression level of inflammatory cytokines IL-1β and IL-6, but significantly increased the level of IL-2 (all P < 0.05). Furthermore, WPH dramatically inhibited the activation of the NF-κB signaling pathway by mitigating the phosphorylation of IκB and p-65 proteins in a dose-dependent manner. The histopathological results indicated that WPH predominately attenuated epidermal hyperplasia, reduced the inflammatory filtration, and promoted collagen deposition in the photoaging skin tissue. Furthermore, WPH significantly stimulated the expression of TGF-β and procollagen type I, and inhibited the MMP-1 activities (all P < 0.05). Overall, the underlying mechanism of WPH ameliorating skin photoaging may be attributed to the synergistic modulation via reversing the inflammatory imbalance, suppressing the activation of the NF-κB signal pathway, stimulating procollagen type I synthesis, and inhibiting MMP-1 activities. According to these results, it can be concluded that WPH has the potential as an anti-photoaging agent in functional foods.
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http://dx.doi.org/10.1039/d0fo02027cDOI Listing
December 2020

IL-32 induces epithelial-mesenchymal transition by triggering endoplasmic reticulum stress in A549 cells.

BMC Pulm Med 2020 Oct 23;20(1):278. Epub 2020 Oct 23.

The First Clinical Medical College, Jinan University, 601 W. Huangpu Avenue, Guangzhou, 510630, China.

Background: Epithelial-mesenchymal transition (EMT) is a key process in the onset and development of idiopathic pulmonary fibrosis (IPF) with unclear mechanisms. Our previous studies found that bleomycin and tunicamycin could induce ER stress and consequently trigger EMT accompanying with IL-32 overexpression. This study was aimed to investigate the effects of IL-32 on EMT and ER stress to elucidate the pathogenesis of IPF.

Methods: Human lung adenocarcinoma A549 cells were treated with recombinant human (rh)IL-32, IL-32 siRNA and EMT inducer tunicamycin, or 4-phenylbutyric acid (4-PBA), respectively. Then the cell morphology was observed and the expression of ER-related markers and EMT-related markers were detected by RT-qPCR or western blotting.

Results: Stimulation of A549 cells with rhIL-32 led to a morphological change from a pebble-like shape to an elongated shape in a portion of the cells, accompanied by down regulated expression of the epithelial cell marker E-cadherin and up regulated expression of the mesenchymal cell markers N-cadherin, Vimentin, and Zeb-1. However, these rhIL-32 induced changes were inhibited by the ER stress inhibitor 4-PBA. Suppression of IL-32 expression with siRNA inhibited TM-induced EMT. Further stimulation of the A549 cells with rhIL-32 demonstrated an increase in the expression of GRP78, although this increase was also inhibited by 4-PBA.

Conclusions: These results suggest that IL-32 induces EMT in A549 cells by triggering ER stress, and IL-32 may be a novel marker for IPF.
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http://dx.doi.org/10.1186/s12890-020-01319-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585222PMC
October 2020

Using organic fertilizers to increase crop yield, economic growth, and soil quality in a temperate farmland.

PeerJ 2020 19;8:e9668. Epub 2020 Aug 19.

State Key Laboratory of Vegetation and Environment Change, Institute of Botany, Chinese Academy of Sciences, Beijing, China.

We used a constant total N application base rate to conduct a two-year field experiment comparing the effects of three organic fertilizers (rapeseed meal (RSM), soybean meal (SBM), and cattle manure (CM)) on the crop yield, economic growth, and soil quality of a winter wheat-summer maize rotation system. Winter wheat and summer maize in rapeseed meal treatment (RSMT), soybean meal treatment (SBMT), and cattle manure treatment (CMT) showed yield increases of 161%, 299%, and 256%, respectively, when compared to no organic fertilizer treatment (CK) ( < 0.05). The annual net incomes of SBMT and CMT were 1.46 and 1.42 times higher, respectively, than RSMT. Compared to the results of the CK group, RSM, SBM, and CM stimulated the soil physically, chemically, and biologically. We found the highest soil macroaggregate proportions, soil organic matter (SOM) levels, total N (TN) levels, and phospholipid fatty acid (PLFA) levels in SBMT. The highest soil pH, microbial biomass carbon (MBC) levels, and microbial biomass nitrogen (MBN) levels were observed in CMT. We used a soil quality index (SQI) to evaluate soil quality. After the two-year fertilization treatments, we calculated the SQI using a minimum data set (MDS). We used SOM levels and actinomycete quantity for the MDS properties. The SQI values were significantly different across the four treatments, with the highest values occurring in SBMT, then CMT and RSMT. In conclusion, SBM and CM were more effective than RSM at maintaining crop yield, economic growth, and soil quality.
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http://dx.doi.org/10.7717/peerj.9668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7443080PMC
August 2020

Antibody Responses and Clinical Outcomes in Adults Hospitalized with Severe COVID-19: A Post hoc Analysis of LOTUS China Trial.

Clin Infect Dis 2020 Aug 25. Epub 2020 Aug 25.

Institute of Respiratory Medicine, Chinese Academy of Medical Science, National Clinical Research Center for Respiratory Diseases, National Center for Respiratory Diseases, Beijing, China.

Background: The characteristics of neutralizing antibodies (NAbs) and antibody against major antigen proteins related to clinical outcomes in severe COVID-19 patients were still less known.

Methods: The neutralizing antibodies (NAbs) and antibodies targeting nucleocapsid (N), spike protein (S), and the receptor-binding domain (RBD) in longitudinal plasma samples from the LOTUS China trial were measured by microneutralization assay and ELISA. Viral load was determined by real-time RT-PCR. A total of 576 plasma and 576 throat swabs were collected from 191 COVID-19 patients. Antibody titers related to adverse outcome and clinical improvement were analysed. Multivariable adjusted generalized linear mixed model for random effects were developed.

Results: After day 28 post symptoms onset, the rate of antibody positivity reached 100% for RBD-IgM, 97.8% for S-IgM, 100% for N-IgG, 100% for RBD-IgG, 91.1% for N-IgM and 91.1% for NAbs. The NAbs titers increased over time in both survivors and non-survivors and correlated to IgG antibodies against N, S and RBD, while its presence showed no statistical correlation with death. N-IgG (slope -2.11, 95% CI -3.04 to -1.18, p&0.0001), S-IgG (slope -2.44, 95% CI -3.35 to -1.54, p&0.0001) and RBD-IgG (slope -1.43, 95% CI -1.98 to -0.88, p&0.0001) were negatively correlated with viral load. S-IgG titers were lower in non-survivors than survivors (p=0.020) at week 4 after symptoms onset.

Conclusions: IgM, IgG against N, S and RBD and NAbs developed in most severe COVID-19 patients, and do not correlate clearly with clinical outcomes. The levels of IgG antibodies against N, S and RBD were related to viral clearance.
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http://dx.doi.org/10.1093/cid/ciaa1247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499517PMC
August 2020

Are College Students' Attitudes Related to Their Application of Sanctions for Campus Sexual Assault Cases?

J Interpers Violence 2020 Aug 4:886260520925789. Epub 2020 Aug 4.

University of Kentucky, Lexington, USA.

With growing attention to adjudication of campus sexual assault cases, more is known regarding students' views of sexual assault, but little the literature focuses on how students perceive "justice" in terms of assigning sanctions or guilt/responsibility for such cases. The present study focused on understanding whether college students' preformed attitudes and beliefs were associated with the severity of sanctions they applied across a range of sexual assault cases as well as their assignments of guilt and responsibility to the parties involved. To determine students' attitudes and beliefs mediating effects on sanction choices, five scales (i.e., rape myth acceptance, downplaying the severity of rape, sexism, just world beliefs, and right-wing authoritarianism) were adapted and used for this project. College students ( = 846) responded to one of four versions of a randomly distributed survey each containing eight vignettes varied to represent levels of 14 factors employed because of their relevance to campus sexual assault cases. Across all versions, sexism was associated with increased responsibility given to the victim. In addition, stronger endorsement of both downplaying significance of rape and rape myth acceptance scales were associated with giving a milder sanction to the perpetrator and increased responsibility and guilt assigned to the victim. Just world beliefs and right-wing authoritarianism associations were inconsistent across the four versions, suggesting these beliefs were situation-specific. Preformed attitudes that are more directly related to the context of sexual assault influenced the designation of sanctions applied to perpetrators and perceptions of guilt and responsibility. Findings are discussed in terms of implications for research and prevention programming.
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http://dx.doi.org/10.1177/0886260520925789DOI Listing
August 2020

Quantitative analysis of bioactive components in walnut leaves by UHPLC-Q-Orbitrap HRMS combined with QAMS.

Food Chem 2020 Nov 30;331:127180. Epub 2020 May 30.

School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, China. Electronic address:

Walnut leaves are rich in phenolic components with antibiotic and antioxidative effects. However, few studies have reported the quantitative analysis of active components in walnut leaf. In this study, a novel method for quantifying the active components in walnut leaves was developed by combining ultra-high performance liquid chromatography-hybrid quadrupole-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) with quantitative analysis of multi-components by a single marker (QAMS). In total, 13 bioactive components were analyzed by a single marker, quercetin. To evaluate the accuracy of this method, an auxiliary quantification method with 13 reference standards was established and validated. The standard method differences (SMDs) of the quantification results between QAMS and the auxiliary method were lower than 20%, indicating that the QAMS method can accurately determine the active components in walnut leaves. This method can provide a reference to address the absence of reference standards for analyzing other foods and herbs.
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http://dx.doi.org/10.1016/j.foodchem.2020.127180DOI Listing
November 2020

Bi-allelic Missense Pathogenic Variants in TRIP13 Cause Female Infertility Characterized by Oocyte Maturation Arrest.

Am J Hum Genet 2020 07 29;107(1):15-23. Epub 2020 May 29.

Institute of Pediatrics, Children's Hospital of Fudan University, the Shanghai Key Laboratory of Medical Epigenetics, the International Co-laboratory of Medical Epigenetics and Metabolism, the Ministry of Science and Technology, the Institutes of Biomedical Sciences, and the State Key Laboratory of Genetic Engineering, Fudan University, Shanghai 200032, China; Shanghai Center for Women and Children's Health, Shanghai 200062, China. Electronic address:

Normal oocyte meiosis is a prerequisite for successful human reproduction, and abnormalities in the process will result in infertility. In 2016, we identified mutations in TUBB8 as responsible for human oocyte meiotic arrest. However, the underlying genetic factors for most affected individuals remain unknown. TRIP13, encoding an AAA-ATPase, is a key component of the spindle assembly checkpoint, and recurrent homozygous nonsense variants and a splicing variant in TRIP13 are reported to cause Wilms tumors in children. In this study, we identified homozygous and compound heterozygous missense pathogenic variants in TRIP13 responsible for female infertility mainly characterized by oocyte meiotic arrest in five individuals from four independent families. Individuals from three families suffered from oocyte maturation arrest, whereas the individual from the fourth family had abnormal zygote cleavage. All displayed only the infertility phenotype without Wilms tumors or any other abnormalities. In vitro and in vivo studies showed that the identified variants reduced the protein abundance of TRIP13 and caused its downstream molecule, HORMAD2, to accumulate in HeLa cells and in proband-derived lymphoblastoid cells. The chromosome mis-segregation assay showed that variants did not have any effects on mitosis. Injecting TRIP13 cRNA into oocytes from one affected individual was able to rescue the phenotype, which has implications for future therapeutic treatments. This study reports pathogenic variants in TRIP13 responsible for oocyte meiotic arrest, and it highlights the pivotal but different roles of TRIP13 in meiosis and mitosis. These findings also indicate that different dosage effects of mutant TRIP13 might result in two distinct human diseases.
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http://dx.doi.org/10.1016/j.ajhg.2020.05.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332649PMC
July 2020

Identifying Invalid Responders in a Campus Climate Survey: Types, Impact on Data, and Best Indicators.

J Interpers Violence 2020 May 13:886260520918588. Epub 2020 May 13.

University of Kentucky, Lexington, USA.

Self-report surveys that are online, lengthy, and contain sensitive material greatly increase the probability of invalid responding (IR) on the instrument. Most research to inform our identification of invalid responders have not been able to test their methodologies where all these conditions are present. This study systematically adopted 10 IR indicators based on direct, archival, and statistic strategies to identify IR providing answers on a lengthy survey collecting campus climate/violence information that college students ( = 6,995) accessed online. Exploratory factor analysis indicated two internal factors (i.e., careless and extreme responding) underlying these IR indicators. Latent class analysis identified 4.8% of the sample as being invalid responders. Compared with honest responders, invalid responders were significantly more likely to report forms of victimization and a greater negative impact from physical abuse or sexual assault. Of importance, mean scores on victimization scales were significantly higher for invalid responders, illustrating the potential for IR data to skew prevalence rates. IR indicators differentially identified honest and invalid responders. The findings of this study contribute to the systematic investigation of IR with college students completing online and lengthy surveys that address sensitive material.
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http://dx.doi.org/10.1177/0886260520918588DOI Listing
May 2020

A cell-based high-throughput screen identifies drugs that cause bleeding disorders by off-targeting the vitamin K cycle.

Blood 2020 08;136(7):898-908

Department of Biology, The University of North Carolina at Chapel Hill, Chapel Hill, NC; and.

Drug-induced bleeding disorders contribute to substantial morbidity and mortality. Antithrombotic agents that cause unintended bleeding of obvious cause are relatively easy to control. However, the mechanisms of most drug-induced bleeding disorders are poorly understood, which makes intervention more difficult. As most bleeding disorders are associated with the dysfunction of coagulation factors, we adapted our recently established cell-based assay to identify drugs that affect the biosynthesis of active vitamin K-dependent (VKD) coagulation factors with possible adverse off-target results. The National Institutes of Health (NIH) Clinical Collection (NCC) library containing 727 drugs was screened, and 9 drugs were identified, including the most commonly prescribed anticoagulant warfarin. Bleeding complications associated with most of these drugs have been clinically reported, but the pathogenic mechanisms remain unclear. Further characterization of the 9 top-hit drugs on the inhibition of VKD carboxylation suggests that warfarin, lansoprazole, and nitazoxanide mainly target vitamin K epoxide reductase (VKOR), whereas idebenone, clofazimine, and AM404 mainly target vitamin K reductase (VKR) in vitamin K redox cycling. The other 3 drugs mainly affect vitamin K availability within the cells. The molecular mechanisms underlying the inactivation of VKOR and VKR by these drugs are clarified. Results from both cell-based and animal model studies suggest that the anticoagulation effect of drugs that target VKOR, but not VKR, can be rescued by the administration of vitamin K. These findings provide insights into the prevention and management of drug-induced bleeding disorders. The established cell-based, high-throughput screening approach provides a powerful tool for identifying new vitamin K antagonists that function as anticoagulants.
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http://dx.doi.org/10.1182/blood.2019004234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426647PMC
August 2020

A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19.

N Engl J Med 2020 05 18;382(19):1787-1799. Epub 2020 Mar 18.

From the Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases (B.C., Yeming Wang, G.F., F.Z., X.G., Z.L., Y.Z., Hui Li, L.S., C.W.), and the Institute of Clinical Medical Sciences (G.F., X.G.), China-Japan Friendship Hospital, the Institute of Respiratory Medicine, Chinese Academy of Medical Sciences (B.C., Yeming Wang, F.Z., Z.L., Y.Z., Hui Li, C.W.), the Clinical and Research Center of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University (Xingwang Li), Peking University Clinical Research Institute, Peking University First Hospital (C.D.), Tsinghua University School of Medicine (Jiuyang Xu), Beijing University of Chinese Medicine (L.S.), NHC Key Laboratory of Systems Biology of Pathogens and Christophe Merieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences (L.G.), and Peking Union Medical College (L.G., C.W.), Beijing, and Jin Yin-tan Hospital, Wuhan (D.W., W.L., Jingli Wang, L.R., B.S., Y.C., M.W., Jiaan Xia, N.C., Jie Xiang, T.Y., T.B., X.X., L.Z., C.L., Y.Y., H.C., Huadong Li, H.H., S.T., F.G., Y.L., Yuan Wei, K.W., K.L., X.Z., X.D., Z.Q., Sixia Lu, X.H., S.R., Shanshan Luo, Jing Wu, Lu Peng, F.C., Lihong Pan, J.Z., C.J., Juan Wang, Xia Liu, S.W., X.W., Q.G., J.H., H.Z., F.Q., C.H., D.Z.) - all in China; Lancaster University, Lancaster (T.J.), and the University of Oxford, Oxford (P.W.H.) - both in the United Kingdom; and the University of Virginia School of Medicine, Charlottesville (F.G.H.).

Background: No therapeutics have yet been proven effective for the treatment of severe illness caused by SARS-CoV-2.

Methods: We conducted a randomized, controlled, open-label trial involving hospitalized adult patients with confirmed SARS-CoV-2 infection, which causes the respiratory illness Covid-19, and an oxygen saturation (Sao) of 94% or less while they were breathing ambient air or a ratio of the partial pressure of oxygen (Pao) to the fraction of inspired oxygen (Fio) of less than 300 mm Hg. Patients were randomly assigned in a 1:1 ratio to receive either lopinavir-ritonavir (400 mg and 100 mg, respectively) twice a day for 14 days, in addition to standard care, or standard care alone. The primary end point was the time to clinical improvement, defined as the time from randomization to either an improvement of two points on a seven-category ordinal scale or discharge from the hospital, whichever came first.

Results: A total of 199 patients with laboratory-confirmed SARS-CoV-2 infection underwent randomization; 99 were assigned to the lopinavir-ritonavir group, and 100 to the standard-care group. Treatment with lopinavir-ritonavir was not associated with a difference from standard care in the time to clinical improvement (hazard ratio for clinical improvement, 1.31; 95% confidence interval [CI], 0.95 to 1.80). Mortality at 28 days was similar in the lopinavir-ritonavir group and the standard-care group (19.2% vs. 25.0%; difference, -5.8 percentage points; 95% CI, -17.3 to 5.7). The percentages of patients with detectable viral RNA at various time points were similar. In a modified intention-to-treat analysis, lopinavir-ritonavir led to a median time to clinical improvement that was shorter by 1 day than that observed with standard care (hazard ratio, 1.39; 95% CI, 1.00 to 1.91). Gastrointestinal adverse events were more common in the lopinavir-ritonavir group, but serious adverse events were more common in the standard-care group. Lopinavir-ritonavir treatment was stopped early in 13 patients (13.8%) because of adverse events.

Conclusions: In hospitalized adult patients with severe Covid-19, no benefit was observed with lopinavir-ritonavir treatment beyond standard care. Future trials in patients with severe illness may help to confirm or exclude the possibility of a treatment benefit. (Funded by Major Projects of National Science and Technology on New Drug Creation and Development and others; Chinese Clinical Trial Register number, ChiCTR2000029308.).
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http://dx.doi.org/10.1056/NEJMoa2001282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7121492PMC
May 2020

Mesenchymal stem/stromal cells-derived IL-6 promotes nasopharyngeal carcinoma growth and resistance to cisplatin via upregulating CD73 expression.

J Cancer 2020 3;11(8):2068-2079. Epub 2020 Feb 3.

Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Dongguan Key Laboratory of Medical Bioactive Molecular Developmental and Translational Research, Guangdong Medical University, Dongguan 523808, China.

Previous studies have implicated the important role of mesenchymal stem/stromal cells (MSCs) within tumor microenvironment (TME) in the pathogenesis and progression of nasopharyngeal carcinoma (NPC), but the potential mechanisms are still unclear. Herein, we showed that an elevated IL-6 level was positively correlated with elevated expression of CD73 in TME of NPC. NPC specimens with an IL-6CD73 phenotype showed higher expression levels of gp80, gp130, p-STAT3, MMP-9 and α-SMA, and clinically, a poorer prognosis than those with an IL-6CD73 phenotype. We found that stimulation with conditioned media derived from IL-6 gene knocked out MSC (MSC-CM) down-regulated the expression of CD73, IL-6, gp80, p-STAT3, and proliferative cell nuclear antigen (PCNA) in CNE-2 NPC cells. Meanwhile, NPC cells co-cultured with MSC-CM were more sensitive to cisplatin than those co-cultured with MSC-CM. Additionally, MSC-derived IL-6 transcriptionally upregulated CD73 expression activating STAT3 signaling pathway in NPC cells. In summary, our findings suggest that MSCs promote NPC progression and chemoresistance by upregulation of CD73 expression activating STAT3 signaling pathway.
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http://dx.doi.org/10.7150/jca.37932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052921PMC
February 2020

Identifying potential active components of walnut leaf that action diabetes mellitus through integration of UHPLC-Q-Orbitrap HRMS and network pharmacology analysis.

J Ethnopharmacol 2020 May 10;253:112659. Epub 2020 Feb 10.

School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, China. Electronic address:

Ethnopharmacological Relevance: Walnut leaf (WL) is a hypoglycemic herbal medication with blood glucose-lowering activity that can affect diabetes mellitus (DM). However, the active components of WL and the mechanisms by which these compounds affect DM are unclear.

Aim Of Study: This study aimed to determine these effective ingredients and elucidate the potential mechanisms by which they affect DM via ultra-high performance liquid chromatography-hybrid quadrupole-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) coupled with network pharmacology analysis.

Materials And Methods: First, UHPLC-Q-Orbitrap HRMS was utilized to identify components of WL. Second, the putative targets of the components were identified and predicted based on chemical similarity and online databases. Third, the key candidate targets and potential active components were identified through topological analysis of a component-disease target interaction network. Finally, interactions between active components and therapeutic targets were confirmed by molecular docking analysis.

Results: One hundred and thirty components were identified in WL, among which 38 were considered potentially bioactive, as they showed hypoglycemic effects. Among these 38, 8 key active components possessed high similarities and shared 4 targets with approved drugs. These findings were confirmed by molecular docking analysis.

Conclusion: The approach combining UHPLC-Q-Orbitrap HRMS with network pharmacology analysis is a rapid and effective tool to identify potentially bioactive constituents in medicinal plants and prescriptions.
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http://dx.doi.org/10.1016/j.jep.2020.112659DOI Listing
May 2020

An ultrathin MoSe photodetector with near-perfect absorption.

Nanotechnology 2020 May 10;31(22):225201. Epub 2020 Feb 10.

Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China, Chengdu 610054, People's Republic of China.

An ultrathin near-perfect MoSe absorber working in the visible regime is demonstrated theoretically and experimentally, and it consists of a MoSe/Au bi-layer film. The polymer-assisted deposition method is used to synthesize MoSe films, which can reduce the roughness and thus improve the film absorption. Simulation results show that the absorption of the absorber with 22 nm MoSe reaches to larger than 90% between 628.5 nm and 718 nm with a peak value up to 99.5% at 686 nm. Moreover, the measured absorption also shows near-perfect absorption of this simple absorber. Finally, an ultrathin photodetector is fabricated based on this perfect absorber and shows on/off reproducibility and remarkable photocurrent, which is three orders of magnitude higher than the dark current.
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http://dx.doi.org/10.1088/1361-6528/ab746fDOI Listing
May 2020

MoRFPred_en: Sequence-based prediction of MoRFs using an ensemble learning strategy.

J Bioinform Comput Biol 2019 12;17(6):1940015

Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan.

Molecular recognition features (MoRFs) usually act as "hub" sites in the interaction networks of intrinsically disordered proteins (IDPs). Because an increasing number of serious diseases have been found to be associated with disordered proteins, identifying MoRFs has become increasingly important. In this study, we propose an ensemble learning strategy, named MoRFPred_en, to predict MoRFs from protein sequences. This approach combines four submodels that utilize different sequence-derived features for the prediction, including a multichannel one-dimensional convolutional neural network (CNN_1D multichannel) based model, two deep two-dimensional convolutional neural network (DCNN_2D) based models, and a support vector machine (SVM) based model. When compared with other methods on the same datasets, the MoRFPred_en approach produced better results than existing state-of-the-art MoRF prediction methods, achieving an AUC of 0.762 on the VALIDATION419 dataset, 0.795 on the TEST45 dataset, and 0.776 on the TEST49 dataset. Availability: http://vivace.bi.a.u-tokyo.ac.jp:8008/fang/MoRFPred_en.php.
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http://dx.doi.org/10.1142/S0219720019400158DOI Listing
December 2019

Responses of weed community, soil nutrients, and microbes to different weed management practices in a fallow field in Northern China.

PeerJ 2019 6;7:e7650. Epub 2019 Sep 6.

State Key Laboratory of Vegetation and Environment Change, Institute of Botany, the Chinese Academy of Sciences, Beijing, China.

The long-term use of herbicides to remove weeds in fallow croplands can impair soil biodiversity, affect the quality of agricultural products, and threaten human health. Consequently, the identification of methods that can effectively limit the weed seed bank and maintain fallow soil fertility without causing soil pollution for the next planting is a critical task. In this study, four weeding treatments were established based on different degrees of disturbance to the topsoil: natural fallow (N), physical clearance (C), deep tillage (D), and sprayed herbicide (H). The changes in the soil weed seed banks, soil nutrients, and soil microbial biomass were carefully investigated. During the fallow period, the C treatment decreased the annual and biennial weed seed bank by 34% against pretreatment, whereas the H treatment did not effectively reduce the weed seed bank. The D treatment had positive effects on the soil fertility, increasing the available nitrogen 108% over that found in the N soil. In addition, a pre-winter deep tillage interfered with the rhizome propagation of perennial weeds. The total biomass of soil bacterial, fungal, and actinomycete in H treatment was the lowest among the four treatments. The biomass of arbuscular mycorrhizal fungi in the N treatment was respectively 42%, 35%, and 91%, higher than that in the C, D, and H treatments. An ecological weeding strategy was proposed based on our findings, which called for exhausting seed banks, blocking seed transmission, and taking advantage of natural opportunities to prevent weed growth for fallow lands. This study could provide a theoretical basis for weed management in fallow fields and organic farming systems.
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http://dx.doi.org/10.7717/peerj.7650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733240PMC
September 2019

Application of Fluorescence in Studying Therapeutic Enzymes.

Adv Exp Med Biol 2019 ;1148:105-114

Department of Chemistry, University of Kentucky, Lexington, KY, USA.

Fluorescence spectroscopy is one of the most important techniques in the study of therapeutic enzymes. The fluorescence phenomenon has been discovered and exploited for centuries, while therapeutic enzymes have been used in treatment of disease for only decades. This chapter provides a brief summary of the current applications of fluorescence methods in studying therapeutic enzymes to provide some insights on the selection of proper method tailored to the goal. First a brief introduction about therapeutic enzymes and history of fluorescence were provided, followed by discussions on how fluorescence was applied in the studies. Four popular fluorescence methods are discussed: fluorescence tracing, fluorescence resonance energy transfer (FRET), fluorescence quenching and fluorescence polarization. Selected application of the fluorescence methods in studying therapeutic enzymes are listed, and discussed in details in the following paragraphs.
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http://dx.doi.org/10.1007/978-981-13-7709-9_5DOI Listing
September 2019

Recurrent Cough and Expectoration for 10 Years: A Case Report.

Glob Pediatr Health 2019 4;6:2333794X19833725. Epub 2019 Apr 4.

The Third Affiliated Hospital of Zunyi Medical College, Zunyi, China.

. Most cases of cystic fibrosis occur in Europe, with only a few occurring in Asia. Pulmonary cystic fibrosis is not a rare disease, but in children it is a potentially life-threatening condition. Children suffering from pulmonary cystic fibrosis rarely survive to adulthood, and responses to treatment are generally poor. The most common cause of cystic fibrosis is a genetic mutation on chromosome 7. A 15-year-old boy with healthy parents suffered from a recurrent cough and expectoration for nearly 10 years. Six years previously, a definitive diagnosis of pulmonary cystic fibrosis and hepatic cirrhosis was made at the Beijing Children's Hospital. The first occurrence of hematemesis occurred 1 year ago. The main symptoms, which caused this period of hospitalization, were cough, expectoration, and hematemesis. The underlying cause was finally determined to be the cystic fibrosis transmembrane conductance regulator gene (p.G970D). After genetic and sweat testing performed at the Beijing Children's Hospital in 2012, a definitive diagnosis of cystic fibrosis was made. The patient was administered hemostatic treatment, antibiotics, and cough relief and sputum reduction therapy. The patient's condition rapidly improved and continued to remain stable, though future relapse is possible following respiratory tract infections. This case indicates that in the case of any child that presents a recurrent cryptogenic cough and expectoration, whether accompanied by hematemesis or not, pulmonary cystic fibrosis should be considered. In order to determine underlying causes and prepare for cystic fibrosis transmembrane conductance regulator modulator therapy, genetic and sweat testing are recommended to be conducted if available.
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http://dx.doi.org/10.1177/2333794X19833725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6449808PMC
April 2019

Metagenomic Analysis of Riesling Grapevine Reveals a Complex Virome Including Two New and Divergent Variants of .

Plant Dis 2019 Jun 1;103(6):1275-1285. Epub 2019 Apr 1.

1 Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario N1G 2W1, Canada.

The virome of a major white wine grape of cultivar Riesling showing decline and leafroll disease symptoms was analyzed through high-throughput sequencing (HTS) using total RNAs as templates and the Illumina HiSeq 2500 platform. Analysis of HTS data revealed the presence of five viruses and three viroids in the infected vine. These viruses are (GLRaV-1) and GLRaV-3 (genus , family ) and three viruses of the family (namely, [GVA], , and [GRSPaV]). We also show that multiple distinct strains of three viruses (GLRaV-3, GVA, and GRSPaV) were present in this diseased grapevine. The complete genomes of two novel and highly divergent isolates of GLRaV-3 were determined using the draft genomes derived from HTS data and two independent rapid amplification of cDNA ends (RACE) strategies to obtain sequences at both the 5' and the 3' termini of the viral genomes. Questionable genome regions of both isolates were also verified through cloning of reverse transcription polymerase chain reaction products and Sanger sequencing. These two isolates are vastly divergent from all other isolates of GLRaV-3 whose genome sequences are available in GenBank. Isolate ON8415A has up to 76% nucleotide sequence identities to other isolates representing existing variant groups. We also revealed high degrees of variation in both length and sequence in the terminal untranslated regions (UTRs) of GLRaV-3 variants. The 5'-UTR of most GLRaV-3 isolates whose complete genomes have been sequenced contain tandem repeats of 65 nucleotides, a highly unusual feature rarely observed in (+)single-stranded RNA viruses. Mechanisms for the biogenesis of these tandem repeats and their function in virus replication and pathogenesis require investigation. Findings of this research add to the genetic diversity, evolutionary biology, and diagnostics of GLRaV-3 that afflicts the global grape wine industry.
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http://dx.doi.org/10.1094/PDIS-09-18-1503-REDOI Listing
June 2019

RNA binding protein PUM2 promotes the stemness of breast cancer cells via competitively binding to neuropilin-1 (NRP-1) mRNA with miR-376a.

Biomed Pharmacother 2019 Jun 23;114:108772. Epub 2019 Mar 23.

Department of Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, China. Electronic address:

Others and ours studies have established the promoting roles of NRP-1 (neuropilin-1) in breast cancer, however, the underlying mechanisms by which NRP-1 is regulated are still confused. Here, bioinformatics analysis indicated that RNA binding protein PUM2 could bind to NRP-1 mRNA. Clinical samples showed that PUM2 expression was significantly increased in breast cancer tissues, negatively correlated with the overall survival and relapse-free survival of breast cancer patients, and positively correlated with NRP-1 expression. Meanwhile, PUM2 expression was remarkably increased in non-adherent spheroids. in vitro experiments demonstrated that PUM2 knockdown attenuated the stemness of breast cancer cells, evident by the decrease of spheroid formation capacity, ALDH1 activity and stemness marker expression. Mechanistically, RNA immunoprecipitation (RIP) and luciferase reporter analysis indicated that PUM2 competitively bound to NRP 3'UTR with miR-376a, which had been previously confirmed by us to suppress the stemness of breast cancer cells, and increased NRP-1 mRNA stability and expression. Furthermore, ectopic expression of NRP-1 or miR-376a knockdown rescued the inhibitory effects of NRP-1 knockdown on the stemness of breast cancer cells. Thus, our results suggest that PUM2 could facilitate the stemness of breast cancer cells by competitively binding to NRP-1 3'UTR with miR-376a.
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http://dx.doi.org/10.1016/j.biopha.2019.108772DOI Listing
June 2019

Identifying short disorder-to-order binding regions in disordered proteins with a deep convolutional neural network method.

J Bioinform Comput Biol 2019 02;17(1):1950004

† Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan.

Molecular recognition features (MoRFs) are key functional regions of intrinsically disordered proteins (IDPs), which play important roles in the molecular interaction network of cells and are implicated in many serious human diseases. Identifying MoRFs is essential for both functional studies of IDPs and drug design. This study adopts the cutting-edge machine learning method of artificial intelligence to develop a powerful model for improving MoRFs prediction. We proposed a method, named as en_DCNNMoRF (ensemble deep convolutional neural network-based MoRF predictor). It combines the outcomes of two independent deep convolutional neural network (DCNN) classifiers that take advantage of different features. The first, DCNNMoRF1, employs position-specific scoring matrix (PSSM) and 22 types of amino acid-related factors to describe protein sequences. The second, DCNNMoRF2, employs PSSM and 13 types of amino acid indexes to describe protein sequences. For both single classifiers, DCNN with a novel two-dimensional attention mechanism was adopted, and an average strategy was added to further process the output probabilities of each DCNN model. Finally, en_DCNNMoRF combined the two models by averaging their final scores. When compared with other well-known tools applied to the same datasets, the accuracy of the novel proposed method was comparable with that of state-of-the-art methods. The related web server can be accessed freely via http://vivace.bi.a.u-tokyo.ac.jp:8008/fang/en_MoRFs.php .
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http://dx.doi.org/10.1142/S0219720019500045DOI Listing
February 2019

Adsorption of heavy metal with modified eggshell membrane and the synthesis of Cu-Ag/modified eggshell membrane composites.

R Soc Open Sci 2018 Sep 19;5(9):180532. Epub 2018 Sep 19.

College of Chemical Engineering, Inner Mongolia University of Technology, Hohhot 010051, People's Republic of China.

The objectives of this study were to remove heavy metals from wastewater through the biosorption method with modified biomass as an effective sorbent and to prepare metal/biomass composites with the same modified biomass as a direct template. Eggshell membrane (ESM) was selected and modified to adsorb heavy metals. Adsorption of metal ions on the modified ESM (MESM) might be attributed to electrostatic interaction, ion exchange and coordination effect with chelating ligands containing N and S on the surface of the MESM. The pH of the solution was a key factor affecting the adsorption. The Cu-Ag/MESM composites with uniform Cu-Ag NPs were prepared with MESM as matrices, and with Cu and Ag adsorbed as metal sources. The Cu-Ag/MESM showed excellent catalytic performance in the reduction of 4-nitrophenol to 4-aminophenol in the aqueous phase. Because of the high stability of the Cu-Ag NPs supported on the macro-dimension supporter, Cu-Ag/MESM can be easily separated after the catalytic reaction and recycled.
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http://dx.doi.org/10.1098/rsos.180532DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6170592PMC
September 2018

Tongmai Yangxin pills anti-oxidative stress alleviates cisplatin-induced cardiotoxicity: Network pharmacology analysis and experimental evidence.

Biomed Pharmacother 2018 Dec 28;108:1081-1089. Epub 2018 Sep 28.

Department of Cardiology, Tianjin Union Medical Center, Tianjin, 300121, China. Electronic address:

Background: Tongmai Yangxin Pills (TMYXP), a traditional Chinese patent medicine, has been widely used to treat coronary heart disease for few decades. However, the potential protective effect of TMYXP on cisplatin-induced cardiotoxicity has not been reported.

Methods: The target proteins corresponding to compounds from Pharmmapper database, PubMed database and ChEMBL database were collected and construct a 'TMYXP-compound-target' network. DAVID database was used for annotation and enrichment pathways and String 9.1 database was used for analysis the protein-protein interaction. Cisplatin-induced rat cardiotoxicity model was established to verify the protective effects mechanism of TMYXP.

Results: The target proteins corresponding to compounds from multiple databases were collected and construct a TCM-compound-target network to enriched pathways with high enrichment score. GO analysis and enrichment clusters point that response of oxidative stress is the main biological process of TMYXP, and Nrf2 signaling pathway and MAPK signaling pathway might be the key functional pathways. In vivo experiments, we proved that TMYXP improves anti-oxidative stress ability and reduce apoptosis through regulating Nrf2/HO-1 pathway and p38-MAPK pathway.

Conclusion: The effects of TMYXP on regulate cardiomyocyte free radical balance and reduce apoptosis, making it possible as a drug candidate for platinum chemotherapeutic induced cardiac injury.
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http://dx.doi.org/10.1016/j.biopha.2018.09.095DOI Listing
December 2018

Expression of c-Myc and Beclin-1 in skin of rats after burn.

Exp Ther Med 2018 Oct 7;16(4):2917-2921. Epub 2018 Aug 7.

Department of Burn and Plastic Surgery, Weifang People's Hospital, Weifang, Shandong 261000, P.R. China.

This study aimed to investigate the expression features of Beclin-1 and c-Myc in the skin burn of rats. A total of 48 Sprague-Dawley (SD) rats were randomly divided into the normal group (n=12), the 3-day burn group (n=12), the 5-day burn group (n=12) and the 7-day burn group (n=12). Except for the normal group, the rat models of burn were established in the other three groups, burn wounds were given routine dressing change, and rats were sacrificed at 3, 5 and 7 days after modeling to collect materials. Then, immunohistochemistry was applied to detect the expression of c-Myc and Beclin-1. The expression levels of c-Myc protein and Beclin-1 protein were measured via western blotting. The expression levels of c-Myc messenger ribonucleic acid (mRNA) and Beclin-1 mRNA were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). In comparison with the normal group, three burn groups had significantly increased the expression of c-Myc and Beclin-1, and the differences were statistically significant (P<0.05). Beclin-1 expression in the 5-day burn group was obviously higher than those in the 3 and 7-day burn groups, and the differences were of statistical significance (P<0.05). The expression of c-Myc in the 7-day burn group was overtly higher than those in the 3 and 5-day burn groups, and the differences showed statistical significance (P<0.05). The expression of Beclin-1 and c-Myc in post-burn skin tissues were gradually increased, with the Beclin-1 expression level reaching the peak on the 5th day after burn, and the expression level of c-Myc was the highest on the 7th day after burn.
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http://dx.doi.org/10.3892/etm.2018.6582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6143901PMC
October 2018

miR-376a inhibits breast cancer cell progression by targeting neuropilin-1 NR.

Onco Targets Ther 2018 30;11:5293-5302. Epub 2018 Aug 30.

Department of Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, People's Republic of China,

Background: The roles and related mechanism of miR-376a in breast cancer cell progression are unclear.

Methods: Kaplan-Meier plotter analysis was used to analyze the correlation between miR-376a and the overall survival (OS) of breast cancer patients. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to detect miR-376a level in breast cancer cells. Cell viability, transwell migration and invasion, and cell apoptosis were constructed to investigate the effects of miR-376a on breast cancer cells. Luciferase reporter and RNA immunoprecipitation (RIP) were used to explore the targeting of miR-376a on NRP-1.

Results: miR-376a expression was positively correlated with the overall survival of breast cancer patients, and significantly decreased in breast cancer cells. Functionally, miR-376a over-expression suppressed cell proliferation, migration and invasion, and promoted cells apoptosis. Additionally, miR-376a could directly target NRP-1 and exerted its effect through NRP-1.

Conclusion: miR-376a could suppress breast cancer cell progression via directly targeting NRP-1.
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http://dx.doi.org/10.2147/OTT.S173416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6124787PMC
August 2018

Survey for major viruses in commercial Vitis vinifera wine grapes in Ontario.

Virol J 2018 08 13;15(1):127. Epub 2018 Aug 13.

Department of Molecular and Cellular Biology, University of Guelph, 50 Stone Road, Guelph, ON, N1G 2W1, Canada.

Background: In recent years, the Ontario grape and wine industry has experienced outbreaks of viral diseases across the province. Little is known about the prevalence of viruses and viral diseases in Ontario. Since 2015, we have conducted large-scale surveys for major viruses in commercial wine grapes in order to obtain a comprehensive understanding of the prevalence and severity of viral diseases in Ontario.

Methods: A total of 657 composite leaf samples representing 3285 vines collected from 137 vine blocks of 33 vineyards from three appellations: Niagara Peninsula, Lake Erie North Shore and Prince Edward County. These samples covered six major red cultivars and five major white grape cultivars. Using a multiplex RT-PCR format, we tested these samples for 17 viruses including those involved in all major viral diseases of the grapevine, such as five grapevine leafroll-associated viruses (GLRaV-1, 2, 3, 4, 7), grapevine red blotch virus (GRBV), grapevine Pinot gris virus (GPGV), grapevine rupestris stem sitting-associated virus (GRSPaV), grapevine virus A (GVA), grapevine virus B (GVB), grapevine fleck virus (GFkV), arabis mosaic virus (ArMV), tomato ringspot virus (ToRSV), trapevine fanleaf virus (GFLV), among others.

Results: Fourteen of the 17 viruses were detected from these samples and the predominant viruses are GRSPaV, GLRaV-3, GFkV, GPGV and GRBaV with an incidence of 84.0, 47.9, 21.8, 21.6 and 18.3%, respectively. As expected, mixed infections with multiple viruses are common. 95.6% of the samples included in the survey were infected with at least one virus; 67% of the samples with 2-4 viruses and 4.7% of the samples with 5-6 viruses. The major grape cultivars all tested positive for these major viruses. The results also suggested that the use of infected planting material may have been one of the chief factors responsible for the recent outbreaks of viral diseases across the province.

Conclusions: This is the first such comprehensive survey for grapevine viruses in Ontario and one of the most extensive surveys ever conducted in Canada. The recent outbreaks of viral diseases in Ontario vineyards were likely caused by GLRaV-3, GRBV and GPGV. Findings from this survey provides a baseline for the grape and wine industry in developing strategies for managing grapevine viral diseases in Ontario vineyards.
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http://dx.doi.org/10.1186/s12985-018-1036-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6090770PMC
August 2018