Publications by authors named "Liyun Zhang"

193 Publications

Drug screening with zebrafish visual behavior identifies carvedilol as a potential treatment for an autosomal dominant form of retinitis pigmentosa.

Sci Rep 2021 Jun 1;11(1):11432. Epub 2021 Jun 1.

Department of Biological Sciences, Purdue University, West Lafayette, IN, 47907, USA.

Retinitis Pigmentosa (RP) is a mostly incurable inherited retinal degeneration affecting approximately 1 in 4000 individuals globally. The goal of this work was to identify drugs that can help patients suffering from the disease. To accomplish this, we screened drugs on a zebrafish autosomal dominant RP model. This model expresses a truncated human rhodopsin transgene (Q344X) causing significant rod degeneration by 7 days post-fertilization (dpf). Consequently, the larvae displayed a deficit in visual motor response (VMR) under scotopic condition. The diminished VMR was leveraged to screen an ENZO SCREEN-WELL REDOX library since oxidative stress is postulated to play a role in RP progression. Our screening identified a beta-blocker, carvedilol, that ameliorated the deficient VMR of the RP larvae and increased their rod number. Carvedilol may directly on rods as it affected the adrenergic pathway in the photoreceptor-like human Y79 cell line. Since carvedilol is an FDA-approved drug, our findings suggest that carvedilol can potentially be repurposed to treat autosomal dominant RP patients.
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http://dx.doi.org/10.1038/s41598-021-89482-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169685PMC
June 2021

Circulating inflammatory biomarkers in adolescents: evidence of interactions between chronic pain and obesity.

Pain Rep 2021 1;6(1):e916. Epub 2021 Apr 1.

Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI, USA.

Introduction: The negative effects of chronic pain and obesity are compounded in those with both conditions. Despite this, little research has focused on the pathophysiology in pediatric samples.

Objective: To examine the effects of comorbid chronic pain and obesity on the concentration of circulating inflammatory biomarkers.

Methods: We used a multiple-cohort observational design, with 4 groups defined by the presence or absence of obesity and chronic pain: healthy controls, chronic pain alone, obesity alone, as well as chronic pain and obesity. Biomarkers measured were leptin, adiponectin, leptin/adiponectin ratio (primary outcome), tumor necrosis factor-alpha, interleukin 6, and C-reactive protein (CRP).

Results: Data on 125 adolescents (13-17 years) were analyzed. In females, there was an interaction between chronic pain and obesity such that leptin and CRP were higher in the chronic pain and obesity group than in chronic pain or obesity alone. Within the chronic pain and obesity group, biomarkers were correlated with worsened pain attributes, and females reported worse pain than males. The highest levels of interleukin 6 and CRP were found in youth with elevated weight and functional disability. We conclude that in adolescents, chronic pain and obesity interact to cause dysregulation of the inflammatory system, and this effect is more pronounced in females.

Conclusion: The augmented levels of inflammatory biomarkers are associated with pain and functional disability, and may be an early marker of future pain and disability.
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http://dx.doi.org/10.1097/PR9.0000000000000916DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8104468PMC
April 2021

Revealing the Structure Evolution of Heterogeneous Pd Catalyst in Suzuki Reaction via the Identical Location Transmission Electron Microscopy.

ACS Nano 2021 May 7;15(5):8621-8637. Epub 2021 May 7.

Shenyang National Laboratory for Materials Science, Institute of Metal Research, Chinese Academy of Sciences, Shenyang 110016, China.

The mechanism of palladium nanoparticles (Pd NPs)-catalyzed cross-coupling reactions has been the subject of intense debate since the recognition of catalytic active sites involving a wide array of dynamic changed Pd species. Here, through the combination of the hot filtration experiment together with the recently developed identical location transmission electron microscopy (IL-TEM) method, the delicate structure evolution of highly dispersed Pd NPs supported on oxygen-functionalized carbon nanotubes (Pd/oCNTs) as well as the kinetics properties of derived dissolved species in liquid phase were systemically investigated in the Suzuki-Miyaura reaction. The result indicates that the leached Pd components caused by the strong adsorption of reactants might have a significant contribution to the coupling products, and the degree for different substrates follows the order of iodobenzene > phenylboronic acid > bromobenzene. Meanwhile, the typical three sequential behaviors of supported Pd NPs, including dissolution, deposition, and growth, along with the increase of the conversion throughout the reaction were spatiotemporally observed by tracking the evolution of individually identifiable NPs. The performed work not only provides direct evidence for the interaction between Pd NPs surface with reactants on atomic scale but also gives a valuable reference for fundamentally understanding the mechanism of the heterogeneous Pd-catalyzed Suzuki coupling process as well as rational design of next-generation catalysts with high efficiency and reusability for synthetic applications.
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http://dx.doi.org/10.1021/acsnano.1c00486DOI Listing
May 2021

Tuning of Reciprocal Carbon-Electrode Properties for an Optimized Hydrogen Evolution.

ChemSusChem 2021 Apr 21. Epub 2021 Apr 21.

Max Planck Institute for Chemical Energy Conversion, Stiftstrasse 34-36, 45470, Mülheim an der Ruhr, Germany.

Closing the material cycle for harmful and rare resources is a key criterion for sustainable and green energy systems. The concept of using scalable biomass-derived carbon electrodes to produce hydrogen from water was proposed here, satisfying the need for sustainability in the field of chemical energy conversion. The carbon electrodes exhibited not only water oxidation activity but also a strong self-oxidation when being used as anode for water splitting. The carbon oxidation, which is more energy-favorable, was intentionally allowed to occur for an improvement of the total current, thus enhancing the hydrogen production on the cathode side. By introducing different earth-abundant metals, the electrode could be well adjusted to achieve an optimized water/carbon oxidation ratio and an appreciable reactivity for practical applications. This promising methodology may become a very large driver for carbon chemistry when waste organic materials or biomass can be converted using its intrinsic energy content of carbon. Such a process could open a safe path for sub-zero CO emission control. The concept of how and which parameter of a carbon-based electrode can be optimized was presented and discussed in this paper.
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http://dx.doi.org/10.1002/cssc.202100654DOI Listing
April 2021

Human umbilical cord mesenchymal stem cell-derived small extracellular vesicles ameliorate collagen-induced arthritis via immunomodulatory T lymphocytes.

Mol Immunol 2021 Jul 12;135:36-44. Epub 2021 Apr 12.

Department of Rheumatology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Shanxi Bethune Hospital Affiliated to Shanxi Medical University, Taiyuan, 030032, China. Electronic address:

Background: Rheumatoid arthritis (RA) is an autoimmune disease for which there are currently no effective therapies. Although mesenchymal stem cells (MSCs) can prevent arthritis through immunomodulatory mechanisms, there are several associated risks. Alternatively, MSC-derived small extracellular vesicles (sEVs) can mimic the effects of MSCs, while reducing the risk of adverse events. However, few studies have examined sEVs in the context of RA. Here, we evaluate the immunomodulatory effects of human umbilical cord MSC (hUCMSC)-derived sEVs on T lymphocytes in a collagen-induced arthritis (CIA) rat model to elucidate the possible mechanism of sEVs in RA treatment. We then compare these mechanisms to those of MSCs and methotrexate (MTX).

Methods: The arthritis index and synovial pathology were assessed. T lymphocyte proliferation and apoptosis, Th17 and Treg proportions, and interleukin (IL)-17, IL-10, and transforming growth factor (TGF)-β expression were detected using flow cytometry. Retinoic acid receptor-related orphan receptor gamma t (RORγt) and forkhead box P3 (FOXP3), which are master transcriptional regulators of Th17 and Treg differentiation, were also assessed using immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR).

Results: sEV treatment ameliorated arthritis and inhibited synovial hyperplasia in a dose-dependent manner. These effects were mediated by inhibiting T lymphocyte proliferation and promoting their apoptosis, while decreasing Th17 cell proportion and increasing that of Treg cells in the spleen, resulting in decreased serum IL-17, and enhanced IL-10 and TGF-β expression. Transcriptionally, sEVs decreased RORγt and increased FOXP3 expression in the spleen, and decreased RORγt and FOXP3 expression in the joints. In some aspects sEVs were more effective than MSCs and MTX in treating CIA.

Conclusions: hUCMSC-derived sEVs ameliorate CIA via immunomodulatory T lymphocytes, and might serve as a new therapy for RA.
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http://dx.doi.org/10.1016/j.molimm.2021.04.001DOI Listing
July 2021

Hydroxychloroquine prophylaxis for preeclampsia, hypertension and prematurity in pregnant patients with systemic lupus erythematosus: A meta-analysis.

Lupus 2021 Jun 15;30(7):1163-1174. Epub 2021 Apr 15.

Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Taiyuan, China.

Objectives: This meta-analysis aimed to evaluate the effectiveness of HCQ in improving the maternal and fetal outcomes in pregnancies with SLE.

Methods: A literature search was conducted using PubMed, MEDLINE, EMBASE, and the Cochrane database for relevant English language articles, and Wanfang, CNKI and VIP for Chinese articles, from the databases' inception to April 30, 2020. These studies compared the maternal and/or fetal outcomes between pregnant patients with SLE who were administered HCQ during pregnancy (HCQ+ group) and those who were not administered HCQ (HCQ- group). Two investigators extracted the data and assessed the quality using the Newcastle-Ottawa Scale (NOS) and GRADE criteria independently. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated. All statistical analyses were conducted using the Stata 12.0 software.

Results: Nine studies involving 1132 pregnancies were included in the study (3 case controls, 2 prospective cohorts, 4 retrospective cohorts). Preeclampsia, gestational hypertension, and prematurity were significantly lower in the HCQ+ group than in the HCQ- group (OR 0.35, 95% CI 0.21-0.59), (OR 0.41, 95% CI 0.19-0.89) and (OR 0.55, 95% CI 0.36-0.86), respectively. There were no significant differences in the rates of HELLP Syndrome (OR 0.88, 95% CI 0.19-3.96), gestational diabetes (OR 2.3, 95% CI 0.44-12.12), thrombotic events (OR 0.26, 95% CI 0.05-1.51), spontaneous abortion (OR 1.77, 95% CI 0.96-3.26), premature rupture of membranes (OR 0.58, 95% CI 0.24-1.39), oligohydramnios (OR 0.90, 95% CI 0.38-2.14), live birth (OR 1.22, 95% CI 0.60-2.47), stillbirth (OR 1.00, 95% CI 0.50-2.00), congenital malformation (OR 0.53, 95% CI 0.14-2.04), low birth weight (OR 0.77, 95% CI 0.43-1.39), intrauterine distress (OR 1.07, 95% CI 0.41-2.76,), intrauterine growth restriction (OR 0.57, 95% CI 0.06-5.43), or five-minute APGAR score <7 (OR 0.72, 95% CI 0.20-2.58) between the two groups.

Conclusions: HCQ treatment during pregnancy could reduce the risk of preeclampsia, pregnancy hypertension and prematurity in SLE patients. The certainty of evidence is high but majority of the studies included are retrospective studies and not randomized controlled trials. Therefore, the multidisciplinary management of pregnant patients with SLE should promote HCQ use, irrespective of disease activity or severity.
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http://dx.doi.org/10.1177/09612033211007199DOI Listing
June 2021

Aptamers: The Powerful Molecular Tools for Virus Detection.

Chem Asian J 2021 Jun 1;16(11):1298-1306. Epub 2021 May 1.

State Key Laboratory of Medicinal Chemical biology, College of Life Sciences, Nankai University, Tianjin, 300350, P. R. China.

Aptamers are short single-stranded DNA or RNA oligonucleotides selected by the technique of systematic evolution of ligands by exponential enrichment (SELEX). Aptamers have been demonstrated to bind various targets from small-molecule to cells or even tissues in the way of antibodies. Thus, they are called chemical antibodies. We summarize and evaluate recent developments in aptamer-based sensors (for short aptasensors) for virus detection in this review. These aptasensors are mainly classified into optical and electronic aptasensors based on the type of transducer. Nowadays, the smartphone has become the most widely used mobile device with billions of users worldwide. Considering the ongoing COVID-19 outbreak, smartphone-based aptasensors for a portable and point-of-care test (POCT) of COVID-19 detection will be of great importance in the future.
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http://dx.doi.org/10.1002/asia.202100242DOI Listing
June 2021

DDAH2 suppresses RLR-MAVS-mediated innate antiviral immunity by stimulating nitric oxide-activated, Drp1-induced mitochondrial fission.

Sci Signal 2021 Apr 13;14(678). Epub 2021 Apr 13.

Department of Immunology, School of Basic Medical Sciences; Advanced Innovation Center for Human Brain Protection, Beijing Key Laboratory for Cancer Invasion and Metastasis, Department of Oncology, Capital Medical University, Beijing 100069, China.

The RIG-I-like receptor (RLR) signaling pathway is pivotal for innate immunity against invading viruses, and dysregulation of this molecular cascade has been linked to various diseases. Here, we identified dimethylarginine dimethylaminohydrolase 2 (DDAH2) as a potent regulator of the RLR-mediated antiviral response in human and mouse. Overexpression of DDAH2 attenuated RLR signaling, whereas loss of DDAH2 function enhanced RLR signaling and suppressed viral replication ex vivo and in mice. Upon viral infection, DDAH2 relocated to mitochondria, where it induced the production of nitric oxide (NO) and the activation of dynamin-related protein 1 (Drp1), which promoted mitochondrial fission and blocked the activation of innate immune responses mediated by mitochondrial antiviral signaling (MAVS). TANK-binding kinase 1 (TBK1), a kinase downstream of MAVS, inhibited DDAH2 by phosphorylating DDAH2 at multiple sites. Our study thus identifies a reciprocal inhibitory loop between the DDAH2-NO cascade and the RLR signaling pathway that fine-tunes the antiviral immune response.
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http://dx.doi.org/10.1126/scisignal.abc7931DOI Listing
April 2021

Human Endogenous Natural Products.

Prog Chem Org Nat Prod 2021 ;114:313-337

Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Synthetic and Functional Biomolecules Center, College of Chemistry and Molecular Engineering, College of Chemistry and Molecular Engineering and Peking-Tsinghua Center for Life Science, Peking University, 282 Chengfu Road, Haidian District, Beijing, China.

Natural products are a class of chemical compounds that are biosynthesized by living organisms, including humans. Endogenous natural products are produced by human cells as well as by the human microbiome. This contribution describes the current understanding and recent progress made on endogenous natural products that are produced by human cells, including amines, steroids, and fatty acid-derived natural products. The co-metabolism and natural product produced by the human microbiome will also be described, including the involvement of tryptophan, bile acids, choline, and cysteine. New strategies and technologies have been introduced that can be applied to identify and characterize those natural products produced by the human microbiome in terms of their composition and physiological function.
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http://dx.doi.org/10.1007/978-3-030-59444-2_4DOI Listing
April 2021

Development of Aptamer-Based Molecular Tools for Rapid Intraoperative Diagnosis and Imaging of Serous Ovarian Cancer.

ACS Appl Mater Interfaces 2021 Apr 31;13(14):16118-16126. Epub 2021 Mar 31.

State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, Tianjin 300350, P. R. China.

Diagnosis and treatment of ovarian cancer are based on intraoperative pathology and debulking surgery. The development of a novel molecular tool is significant for rapid intraoperative pathologic diagnosis, which instructs the decision-making on excision surgery and effective chemotherapy. In this work, we represent a DNA aptamer named mApoc46, which is generated from cell-SELEX by targeting patient-derived primary serous ovarian cancer (pSOC) cells. An average dissociation constant () was determined to be 0.15 ± 0.05 μM by flow cytometry. The mApoc46 aptamer displays a robust specificity to pSOC cells. Labeled with FAM, mApoc46 can selectively stain living pSOC cells in 30 min without staining commercial OC cell lines and cell lines associated with other cancers. Interestingly, FAM-mApoc46 displayed superb selectivity toward high-grade serous ovarian cancer (HG-SOC) tissues in frozen sections against low-grade SOC, ovarian borderline tumor, other nonepithelial ovarian tumors, and healthy ovarian tissue. These results lead to a potential application in the identification of OCs' histological subtypes during operation. In the patient-derived tumor xenograft NCG mice model, Cy5-labeled mApoc46 was found to accumulate at the tumor area and served as an imaging probe. The mApoc46 probe shows a robust and stable performance to visualize SOC tumors in the body. Therefore, aptamer mApoc46 holds great potential in rapid intraoperative detection, pathological diagnosis, fluorescence image-guided cancer surgery, and targeted drug delivery and therapy.
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http://dx.doi.org/10.1021/acsami.1c02072DOI Listing
April 2021

Venovenous Versus Venoarterial Extracorporeal Membranous Oxygenation in Inotrope Dependent Pediatric Patients With Respiratory Failure.

ASAIO J 2021 04;67(4):457-462

From the Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI.

Patients with respiratory failure requiring inotropes or vasopressors are often placed on venoarterial (VA) extracorporeal membrane oxygenation (ECMO), as venovenous (VV) ECMO does not provide direct circulatory support. This retrospective multicenter study compared outcomes for 103 pediatric patients, with hemodynamic compromise, placed on VV ECMO for respiratory failure to those placed on VA ECMO. The primary outcome was survival to hospital discharge. Fifty-seven (55%) study participants were supported on VV ECMO. The two groups had similar PRISM III scores at pediatric intensive care unit (PICU) admission, and vasoactive-inotropic scores at ECMO cannulation. More VV ECMO patients received inhaled nitric oxide (iNO) (54.4 vs. 34.8%; p = 0.04) and had a higher oxygenation index (median 41.5 vs. 19.5; p = 0.04) pre-ECMO. More VA ECMO patients had cardiac dysfunction and cardiac arrest pre-ECMO (50 vs. 14%; p < 0.0001). In univariable analysis, survival to hospital discharge was higher in the VV vs. VA ECMO group (72 vs. 44%; p = 0.005), however, in multivariable models, cannulation type was confounded by cardiopulmonary resuscitation and was not independently associated with survival. VV survivors had longer ECMO duration compared with VA survivors (median, 7 vs. 4.5 days; p = 0.036) but similar PICU and hospital days. No significant difference was noted in functional outcomes or comorbidities at discharge. Cannulation type is not independently associated with survival to hospital discharge in pediatric patients on vasoactive infusions at the time of ECMO cannulation for respiratory indications.
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http://dx.doi.org/10.1097/MAT.0000000000001254DOI Listing
April 2021

Establishing Classification Tree Models in Rheumatoid Arthritis Using Combination of Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry and Magnetic Beads.

Front Med (Lausanne) 2021 24;8:609773. Epub 2021 Feb 24.

Department of Rheumatology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Shanxi Bethune Hospital Affiliated to Shanxi Medical University, Taiyuan, China.

There is no simple method for early diagnosis and evaluation of rheumatoid arthritis (RA). This study aimed to determine potential biomarkers and establish diagnostic patterns for RA using proteomic fingerprint technology combined with magnetic beads. The serum protein profiles of 97 RA patients and 76 healthy controls (HCs) were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) with weak cationic exchange (WCX) magnetic beads. Samples were randomly divided into training (83 RA patients and 56 HCs) and test sets (14 RA patients and 20 HCs). Patients were classified according to their Disease Activity Score: in remission, = 28; with low disease activity, = 17; with moderate disease activity, = 21; with high disease activity, = 31. There are 44 RA patients alone, 22 RA patients with interstitial lung disease (RA-ILD), 18 RA patients with secondary Sjögren's syndrome (RA-sSS), 6 RA patients with osteonecrosis of the femoral head (RA-ONFH), and 7 RA patients with other complications. Eleven patients were treated with etanercept only for half a year, after which their serum protein profiles were detected. The proteomic pattern was identified by Biomarker Patterns Software, and the potential biomarkers for RA diagnosis were further identified and quantified by enzyme-linked immunosorbent assay. The diagnostic pattern with four potential protein biomarkers, mass-to-charge (m/z) 3,448.85, 4,716.71, 8,214.29, and 10,645.10, could accurately recognize RA patients from HCs (specificity, 91.57%; sensitivity, 92.86%). The test set were correctly classified by this model (sensitivity, 95%; specificity, 100%). The components containing the four biomarkers were preliminarily retrieved through the ExPasy database, including the C-C motif chemokine 24 (CCL24), putative metallothionein (MT1DP), sarcolipin (SLN), and C-X-C motif chemokine 11 (CCXL11). Only the CCL24 level was detected to have a significant decrease in the serum of RA patients as compared with HCs ( < 0.05). No significant difference was found in others, but a decreasing trend consistent with the down-regulation of the four biomarkers detected by MALDI-TOF-MS was observed. The diagnostic models could effectively discriminate between RA alone and RA with complications (RA-ILD: m/z 10,645.10 and 12,595.86; RA-sSS: m/z 6,635.62 and 33,897.72; RA-ONFH: m/z 2,071.689). The classification model, including m/z 1,130.776, 1,501.065, 2,091.198, and 11,381.87, could distinguish between RA patients with disease activity and those in remission. RA with low disease activity could be efficiently discriminated from other disease activity patients by specific protein biomarkers (m/z 2,032.31, 2,506.214, and Z9286.495). Two biomarkers (m/z 2,032.31 and 4,716.71) were applied to build the classification model for RA patients with moderate and high disease activities. Biological markers for etanercept (m/z 2,671.604064, 5,801.840579, 8,130.195641, and 9,286.49499) were observed between the responder ( = 7) and non-responder groups ( = 4) ( < 0.05). We successfully established a series of diagnostic models involving RA and RA with complications as well as assessed disease activity. Furthermore, we found that CCL24 may be a valuable auxiliary diagnostic indicator for RA. These results provide reference values for clinical practice in the future.
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http://dx.doi.org/10.3389/fmed.2021.609773DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943484PMC
February 2021

Maternal high-salt diet during pregnancy impairs synaptic plasticity and memory in offspring.

FASEB J 2021 Apr;35(4):e21244

Department of Neurobiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, P.R. China.

Excess salt intake harms the brain health and cognitive functions, but whether a maternal high-salt diet (HSD) affects the brain development and neural plasticity of offspring remains unclear. Here, using a range of behavioral tests, we reported that the offspring of maternal HSD subjects exhibited short- and long-term memory deficits, especially in spatial memory in adulthood. Moreover, impairments in synaptic transmission and plasticity in the hippocampus were observed in adult offspring by using in vivo electrophysiology. Consistently, the number of astrocytes but not neurons in the hippocampus of the offspring from the HSD group were significantly decreased, and ERK and AKT signaling pathways involved in neurodevelopment were highly activated only during juvenile. In addition, the expression of synaptic proteins decreased both in juvenile and adulthood, and this effect might be involved in synaptic dysfunction. Collectively, these data demonstrated that the maternal HSD might cause adult offspring synaptic dysfunction and memory loss. It is possibly due to the reduction of astrocytes in juvenile.
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http://dx.doi.org/10.1096/fj.202001890RDOI Listing
April 2021

Designing nanofibrous membrane with biomimetic caterpillar-like structured for highly-efficient and simultaneous removal of insoluble emulsified oils and soluble dyes towards sewage remediation.

J Hazard Mater 2021 07 17;414:125442. Epub 2021 Feb 17.

State Key Lab of Oil and Gas Reservoir Geology and Exploitation, Southwest Petroleum University, Chengdu 610500, PR China.

Purification of insoluble emulsified oils and soluble organic pollutants from sewage has attracted tremendous attention in today's society. Herein, a stable and environmentally friendly nanofibrous membrane with hierarchical caterpillar-like structure was fabricated via in-situ hydrothermal growing the nickel-cobalt layered double hydroxides (NiCo-LDHs) on tche polyacrylonitrile (PAN) electrospun nanofibers. The wrapped hydrophilic NiCo-LDHs constructed the hierarchical structure and endowed the membrane attractive superhydrophilicity (≈ 0°)/underwater superoleophobicity (≈ 161°) and enhanced oil-repellency performance. Meanwhile, the [email protected]/oPAN NFMs can display the ultra-fast flux of SSEs (xylene/water emulsion, 4175 L m h) and satisfactory separation efficiency (99.07%). Moreover, the introduction of positively charged NiCo-LDHs increased plentiful adsorption active sites for membranes, which is beneficial to demulsify ionic SSEs and adsorb organic pollutants. Finally, for simultaneous purification of complex sewage by the dead-end and cross-flow filtration experiment, the composite membrane both displayed splendid removal rate of oil (> 99.0%) and dyes (> 99.0%), robust regeneration recycle-ability and no secondary pollution. Hence, it is expected that such strategy of combining electrospun and chelating-assisted in-situ hydrothermal can provide a low energy consumption and high decontamination technology for severe environmental crisis.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125442DOI Listing
July 2021

[email protected] Robustly Decorated PVDF Membrane Prepared by a Bioinspired Accurate-Deposition Strategy for Complex Corrosive Wastewater Treatment.

ACS Appl Mater Interfaces 2021 Mar 24;13(9):11320-11331. Epub 2021 Feb 24.

State Key Laboratory of Oil & Gas Reservoir Geology and Exploitation, Southwest Petroleum University, Chengdu, Sichuan610500, China.

As industrialization has spread all around the world, the problems of water pollution such as offshore oil spill and industrial sewage discharge have spread with it. Although many new separation materials have been successfully developed to deal with this crisis, a large number of water treatment materials only focus on the treatment of classified single water pollutant under mild conditions. It is a great challenge to treat soluble contaminants such as water-soluble dyes and insoluble contaminants, for example, emulsified oils simultaneously in a strong corrosive environment. Herein, in this work, corrosive resistance and multifunctional surface on a commercial polyvinylidene difluoride (PVDF) membrane via a tunicate-inspired gallic acid-assisted accurate-deposition strategy is created. Owing to the titanium-carboxylic coordination bonding and accurate-deposition strategy, the as-prepared membrane exhibits extraordinary stability, facing various harsh environmental challenges and incredibly corrosive situations (e.g., 4 M NaOH, 4 M HCl, and saturated NaCl solution). The robust multifunctional surface also endows commercial PVDF membrane with the ability for in situ separation and adsorption of surfactant-stabilized oil-in-water (corrosive and dyed) emulsions with high adsorption efficiencies up to 99.9%, separation efficiencies above 99.6%, and permeation flux as high as 15,698 ± 211 L/(m·h·bar). Furthermore, the resultant membrane can be regenerated facilely and rapidly by flushing a small amount of HCl (4 M) or NaOH (4 M), making the corrosive resistance membrane attain a long-term and high-efficiency application for complex dyed wastewater treatment. Therefore, the multifunctional membrane has a broad application prospect in the industrial field.
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http://dx.doi.org/10.1021/acsami.1c00697DOI Listing
March 2021

Design of a workstation based on a human-interfacing robot for occupational health and safety.

Work 2021 ;68(3):863-870

Wenzhou Kean University, Wenzhou, China.

Background: Robots communicate with the physical world program with the mechanic's simulations. They recommend that people-to-people robotics will prepare for cognitive models. Presently, there is a considerable concern for greater flexibility and efficiency in the scope of human-robot interfacing collaboration across hospitals. Nevertheless, interfacing is still in its infancy in manufacturing; industrial practitioners have many questions and doubts about the efficiency of the device and the health of human operators.

Objectives: Therefore, research on processes and methods of design is required to ensure that the intended human-computer interaction-based workstations effectively meet system performance, human safety, and ergonomics standards for realistic applications. This study provides a design process for a workstation appropriate for occupational health and safety. This article outlines the perspectives learned from incorporation into the preparation and operation of robotics of digital cognitive models.

Results: This ends with an overarching game-theoretical model of contact and analyses how different approaches contribute to effective communicating activities for the robot in its interaction with people.

Conclusion: The new feature of this design process is the approach for testing alternative workstation designs, taking into account efficiency and safety features with computer simulations.
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http://dx.doi.org/10.3233/WOR-203420DOI Listing
January 2021

Comprehensive Characterization of Bile Acids in Human Biological Samples and Effect of 4-Week Strawberry Intake on Bile Acid Composition in Human Plasma.

Metabolites 2021 Feb 10;11(2). Epub 2021 Feb 10.

Department of Food Science and Nutrition and Center for Nutrition Research, Institute for Food Safety and Health, Illinois Institute of Technology, Chicago, IL 60616, USA.

Primary bile acids (BAs) and their gut microbial metabolites have a role in regulating human health. Comprehensive characterization of BAs species in human biological samples will aid in understanding the interaction between diet, gut microbiota, and bile acid metabolism. Therefore, we developed a qualitative method using ultra-high performance liquid chromatography (UHPLC) coupled with a quadrupole time-of-flight (Q-TOF) to identify BAs in human plasma, feces, and urine samples. A quantitative method was developed using UHPLC coupled with triple quadrupole (QQQ) and applied to a previous clinical trial conducted by our group to understand the bile acid metabolism in overweight/obese middle-aged adults ( = 34) after four weeks strawberry vs. control intervention. The qualitative study tentatively identified a total of 81 BAs in human biological samples. Several BA glucuronide-conjugates were characterized for the first time in human plasma and/or urine samples. The four-week strawberry intervention significantly reduced plasma concentrations of individual secondary BAs, deoxycholic acid, lithocholic acid and their glycine conjugates, as well as glycoursodeoxycholic acid compared to control ( < 0.05); total glucuronide-, total oxidized-, total dehydroxyl-, total secondary, and total plasma BAs were also lowered compared to control ( < 0.05). The reduced secondary BAs concentrations suggest that regular strawberry intake modulates the microbial metabolism of BAs.
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http://dx.doi.org/10.3390/metabo11020099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916557PMC
February 2021

Age differences in secular trends in black-white disparities in mortality from systemic lupus erythematosus among women in the United States from 1988 to 2017.

Lupus 2021 Apr 3;30(5):715-724. Epub 2021 Feb 3.

Department of Public Health, National Cheng Kung University, Tainan, Taiwan.

Objective: To examine the age differences in secular trends in black-white disparities in mortality from systemic lupus erythematosus (SLE) among women in the United States from 1988 to 2017.

Methods: We used mortality data to calculate age-specific SLE and all-causes (as reference) mortality rates and black/white mortality rates ratios among women from 1988 to 2017. Annual percent change was estimated using joinpoint regression analysis.

Results: We identified 10,793 and 4,165,613 black women and 19,455 and 31,129,528 white women who died between 1988 and 2017 from SLE and all-causes, respectively. The black/white SLE mortality rate ratio according joinpoint regression model was 6.6, 7.2, 4.4, and 1.4 for decedents aged 0-24, 25-44, 45-64, and 65+ years in 1988 and was 7.2, 5.9, 4.1, and 1.9, respectively in 2017. No significant decline trend was noted and the annual percent change was 0.3%, -0.7%, -0.2%, and 1.0%, respectively. On the contrast, the black/white all-causes mortality rate ratio was 2.0, 2.5, 1.8, and 1.0, respectively in 1988 and was 1.7, 1.3, 1.5, and 0.9, respectively in 2017, a significant decline trend was noted in each age group.

Conclusions: Black adults, youths and adolescents had four to seven times higher SLE mortality rates than their white counterparts and the black-white disparities persisted during the past three decades. On the contrast, black women had less than two times higher all-causes mortality rates than their white counterparts and black-white disparities significantly diminish during the past three decades.
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http://dx.doi.org/10.1177/0961203321988936DOI Listing
April 2021

Fibroblast-like synoviocytes in rheumatoid arthritis: Surface markers and phenotypes.

Int Immunopharmacol 2021 Apr 30;93:107392. Epub 2021 Jan 30.

Department of Rheumatology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, PR China. Electronic address:

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that mainly affects synovial joints. During the course of RA, the synovium transforms into hyperplastic invasive tissue, leading to cartilage and bone destruction. Fibroblast-like synoviocytes (FLS) in the synovial lining develop aggressive phenotypes and produce pathogenic mediators that lead to the occurrence and progression of disease, playing a major role in RA pathophysiology. Therefore, research on FLS has become the main focus within the RA field. With technical advances and the development of multi-omics comprehensive analysis approaches, it has become possible to identify different FLS subsets via high-throughput sequencing and investigate differences between FLS phenotypes, allowing for the detailed study of RA pathogenesis. This review summarizes recent works on FLS subtypes and the surface marker proteins identified for different subtypes, providing a theoretical basis and reference for future studies on FLS in RA. The current work also addresses the clinical potential of FLS surface markers in RA based on related research from other fields.
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http://dx.doi.org/10.1016/j.intimp.2021.107392DOI Listing
April 2021

Pentraxin 3 is more accurate than C-reactive protein for Takayasu arteritis activity assessment: A systematic review and meta-analysis.

PLoS One 2021 2;16(2):e0245612. Epub 2021 Feb 2.

Department of Rheumatology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Taiyuan, Shanxi, China.

Aims: Whether the circulating levels of pentraxin 3 (PTX3), an acute phase reactant (APR), are higher in active Takayasu arteritis (TAK), and if so, whether PTX3 is more accurate than C-reactive protein (CRP) in TAK activity assessment has been investigated in this study.

Study Design: Research works such as PubMed, Embase, ScienceDirect, Cochrane Library, and two Chinese literature databases (CNKI and WanFang) were searched for studies conducted till August 30th, 2019. Two investigators searched the studies independently, who evaluated the quality of the study using the Newcastle-Ottawa scale (NOS) and extracted data. Pooled standard mean difference (SMD) and diagnostic indexes, with a 95% confidence interval (CI), were calculated using a random-effect model.

Results: Totally, 8 studies involving 473 TAK (208 active and 265 inactive TAK) patients and 252 healthy controls were eventually included in the meta-analysis. PTX3 level in the blood in active TAK patients were found to be higher than that in dormant TAK with pooled SMD of 0.761 (95% CI = 0.38-1.14, p<0.0001; I2 = 68%, p of Q test = 0.003). And there was no publication bias. Among the 8 studies, 5 studies identified active TAK with both PTX3 and CRP. The pooled sensitivity, specificity, and AUC values of PTX3 in active TAK diagnosis were higher than those of CRP (0.78 [95% CI = 0.65-0.87] vs. 0.66 [95% CI = 0.53-0.77], p = 0.012; 0.85 [95% CI = 0.77-0.90] vs. 0.77 [95% CI = 0.56-0.90], p = 0.033; 0.88 [95% CI = 0.85-0.90] vs. 0.75 [95% CI = 0.71-0.79], p < 0.0001). It showed potential publication bias using Egger's test (p of PTX3 = 0.031 and p of CRP = 0.047).

Conclusions: PTX3 might be better than CRP in the assessment of TAK activity. Yet, it should be cautious before clinical use for moderate heterogeneity and potential publication bias of the meta-analysis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245612PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7853471PMC
February 2021

Superoxide radical enhanced photocatalytic performance of styrene alters its degradation mechanism and intermediate health risk on TiO/graphene surface.

Environ Res 2021 04 19;195:110747. Epub 2021 Jan 19.

Guangdong Key Laboratory of Environmental Catalysis and Health Risk Control, Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, Institute of Environmental Health and Pollution Control, Guangdong University of Technology, Guangzhou, 510006, China; Guangzhou Key Laboratory of Environmental Catalysis and Pollution Control, Key Laboratory of City Cluster Environmental Safety and Green Development, School of Environmental Science and Engineering, Guangdong University of Technology, Guangzhou, 510006, China. Electronic address:

Enhancement of reactive oxygen species (ROS) on semiconductor coupled by carbon material promotes photocatalytic performance toward aromatic hydrocarbons, while the contribution to their degradation mechanism and health risk is not well understood. Herein, photocatalytic degradation of styrene on TiO and TiO/reduced graphene oxide (TiO/rGO) surface is compared under dry air condition to investigate the role of ·O in styrene degradation. TiO/rGO shows 4.8 times higher degradation efficiency than that of TiO, resulting in 16% reduced production of intermediates with identical composition. The improved formation of ·O on TiO/rGO is confirmed responsible for these variations. Theoretical calculation further reveals the enhancement of ·O thermodynamically favoring conversion of styrene to acetophenone, turning the most dominant intermediate from benzoic acid on TiO to acetophenone on TiO/rGO. The accumulated formation of acetophenone on TiO/rGO poses increased acute threat to human beings. Our findings proclaim that ROS promoted photocatalytic performance of semiconductor after carbon material composition ultimately changes the priority order of degradation pathways to form by-product with higher threat toward human beings. And more attentions are advised focusing on the relevance with degradation efficiency, intermediate and toxicity of aromatic hydrocarbons on carbon material based photocatalyst.
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http://dx.doi.org/10.1016/j.envres.2021.110747DOI Listing
April 2021

The role of SARS-CoV-2 target ACE2 in cardiovascular diseases.

J Cell Mol Med 2021 02 14;25(3):1342-1349. Epub 2021 Jan 14.

Department of Cardiovascular Surgery, The First Affiliated Hospital, The Air Force Medical University, Xi'an, China.

SARS-CoV-2, the virus responsible for the global coronavirus disease (COVID-19) pandemic, attacks multiple organs of the human body by binding to angiotensin-converting enzyme 2 (ACE2) to enter cells. More than 20 million people have already been infected by the virus. ACE2 is not only a functional receptor of COVID-19 but also an important endogenous antagonist of the renin-angiotensin system (RAS). A large number of studies have shown that ACE2 can reverse myocardial injury in various cardiovascular diseases (CVDs) as well as is exert anti-inflammatory, antioxidant, anti-apoptotic and anticardiomyocyte fibrosis effects by regulating transforming growth factor beta, mitogen-activated protein kinases, calcium ions in cells and other major pathways. The ACE2/angiotensin-(1-7)/Mas receptor axis plays a decisive role in the cardiovascular system to combat the negative effects of the ACE/angiotensin II/angiotensin II type 1 receptor axis. However, the underlying mechanism of ACE2 in cardiac protection remains unclear. Some approaches for enhancing ACE2 expression in CVDs have been suggested, which may provide targets for the development of novel clinical therapies. In this review, we aimed to identify and summarize the role of ACE2 in CVDs.
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http://dx.doi.org/10.1111/jcmm.16239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875924PMC
February 2021

Identification of Metabolism-Associated Prostate Cancer Subtypes and Construction of a Prognostic Risk Model.

Front Oncol 2020 26;10:598801. Epub 2020 Nov 26.

Department of Urology, First Hospital of Shanxi Medical University, Taiyuan, China.

Background: Despite being the second most common tumor in men worldwide, the tumor metabolism-associated mechanisms of prostate cancer (PCa) remain unclear. Herein, this study aimed to investigate the metabolism-associated characteristics of PCa and to develop a metabolism-associated prognostic risk model for patients with PCa.

Methods: The activity levels of PCa metabolic pathways were determined using mRNA expression profiling of The Cancer Genome Atlas Prostate Adenocarcinoma cohort single-sample gene set enrichment analysis (ssGSEA). The analyzed samples were divided into three subtypes based on the partitioning around medication algorithm. Tumor characteristics of the subsets were then investigated using t-distributed stochastic neighbor embedding (t-SNE) analysis, differential analysis, Kaplan-Meier survival analysis, and GSEA. Finally, we developed and validated a metabolism-associated prognostic risk model using weighted gene co-expression network analysis, univariate Cox analysis, least absolute shrinkage and selection operator, and multivariate Cox analysis. Other cohorts (GSE54460, GSE70768, genotype-tissue expression, and International Cancer Genome Consortium) were utilized for external validation. Drug sensibility analysis was performed on Genomics of Drug Sensitivity in Cancer and GSE78220 datasets. In total, 1,039 samples and six cell lines were concluded in our work.

Results: Three metabolism-associated clusters with significantly different characteristics in disease-free survival (DFS), clinical stage, stemness index, tumor microenvironment including stromal and immune cells, DNA mutation ( and ), copy number variation, and microsatellite instability were identified in PCa. Eighty-four of the metabolism-associated module genes were narrowed to a six-gene signature associated with DFS, , , , , , and (p <0.05). A risk model was developed, and external validation revealed the strong robustness our risk model possessed in diagnosis and prognosis as well as the association with the cancer feature of drug sensitivity.

Conclusions: The identified metabolism-associated subtypes reflected the pathogenesis, essential features, and heterogeneity of PCa tumors. Our metabolism-associated risk model may provide clinicians with predictive values for diagnosis, prognosis, and treatment guidance in patients with PCa.
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http://dx.doi.org/10.3389/fonc.2020.598801DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726320PMC
November 2020

Gastric emptying in healthy children using the Spirulina breath test: The impact of gender, body size, and pubertal development.

Neurogastroenterol Motil 2021 Jun 10;33(6):e14063. Epub 2020 Dec 10.

Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Medical College of Wisconsin, Milwaukee, WI, USA.

Background: There are no pediatric norms for gastric emptying (GE) measured by nuclear scintigraphy. The C-labeled, stable isotope GE breath test (GEBT) is a non-radioactive alternative. We aimed to determine normative GEBT ranges in a cohort of healthy children and examine the influence of age, gender, puberty, and body surface area (BSA).

Methods: Healthy children ages 8-18 years completed the [ C]-Spirulina platensis GEBT after an overnight fast. Breath samples were collected at baseline, every 15 min × 1 h, then every 30 min for 4 h total. The CO excretion rate was determined by the change in CO / CO over time in each breath sample, expressed as kPCD (Percent C Dose excreted/min). A mixed model with random time was used for multivariable analysis and outcome fit into a quadratic model.

Key Results: The 100 subjects completed the test meal within allotted time. Median (IQR) age was 13.5 (11.3-15.5) years; 51% were female. Females had lower CO excretion rates (slower GE) than males across time (p < 0.001) while decreased excretion rates correlated with higher BSA (p = 0.015). Gender differences were also noted within pubertal stages with females showing slower GE. Multivariable analysis suggested that pre-pubertal children have faster GE than both peri- and post-pubertal groups (p < 0.0001).

Conclusions & Inferences: Gender, puberty, and BSA influence GE rates in healthy children more than age. Although further data are needed, pubertal stage and hormonal influences may be unique factors to consider when assessing GE in children.
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http://dx.doi.org/10.1111/nmo.14063DOI Listing
June 2021

Pharmacokinetic Characterization of (Poly)phenolic Metabolites in Human Plasma and Urine after Acute and Short-Term Daily Consumption of Mango Pulp.

Molecules 2020 Nov 25;25(23). Epub 2020 Nov 25.

Department of Food Science and Nutrition, Center for Nutrition Research, Institute for Food Safety and Health, Illinois Institute of Technology, Chicago, IL 60616, USA.

Pharmacokinetic (PK) evaluation of polyphenolic metabolites over 24 h was conducted in human subjects ( = 13, BMI = 22.7 ± 0.4 kg/m) after acute mango pulp (MP), vitamin C (VC) or MP + VC test beverage intake and after 14 days of MP beverage intake. Plasma and urine samples were collected at different time intervals and analyzed using targeted and non-targeted mass spectrometry. The maximum concentrations (C) of gallotannin metabolites were significantly increased ( < 0.05) after acute MP beverage intake compared to VC beverage alone. MP + VC beverage non-significantly enhanced the C of gallic acid metabolites compared to MP beverage alone. Pyrogallol (microbial-derived metabolite) derivatives increased (3.6%) after the 14 days of MP beverage intake compared to 24 h acute MP beverage intake ( < 0.05). These results indicate extensive absorption and breakdown of gallotannins to galloyl and other (poly)phenolic metabolites after MP consumption, suggesting modulation and/or acclimation of gut microbiota to daily MP intake.
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http://dx.doi.org/10.3390/molecules25235522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7728344PMC
November 2020

The long-term prognosis of pneumomediastinum associated with dermatomyositis: a two-centre retrospective cohort study.

Rheumatology (Oxford) 2021 May;60(5):2288-2295

Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, National Clinical Research Center for Dermatologic and Immunologic Diseases, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.

Objectives: Pneumomediastinum (PnM) is a rare but life-threatening complication of DM. The present study aims to characterize the long-term prognosis and prognostic factors of DM-associated PnM.

Methods: Inpatients with DM-associated PnM were retrospectively enrolled from two tertiary referral centres for rheumatic disease. The enrolled patients were divided into survivors or non-survivors. Information about the demographics, clinical manifestations, CT scan features, laboratory findings and outcomes were collected from their medical records. A least absolute shrinkage and selection operator regularized Cox regression model was used to select the most relevant factors. Prognosis was analysed using a Kaplan-Meier curve. A Cox proportional hazards model was used to identify independent predictive factors for long-term survival.

Results: A total of 62 patients (26 women) with DM-associated PnM were enrolled. The mean age was 44.3 years (s.d. 11.7). The median follow-up duration was 17 days (quartiles 7, 266.5). Thirty-five patients died during follow-up. The survival rates were 75.4% at 1 week, 46.2% at 3 months and 41.9% at 1 year. The Cox proportional hazards model identified the development of fever [hazard ratio (HR) 3.23 (95% CI 1.25, 8.35), P = 0.02] and a decrease in the number of lymphocytes [HR 2.19 (95% CI 1.10, 4.39), P = 0.03] as independent risk factors for death.

Conclusion: The results suggest poor overall survival among patients with DM-associated PnM. Survival during the first 3 months is crucial for long-term survival. Meanwhile, the development of fever and a decrease in the number of lymphocytes were associated with long-term mortality. Early recognition and prompt treatment of this high-risk group of DM patients is therefore important.
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http://dx.doi.org/10.1093/rheumatology/keaa582DOI Listing
May 2021

Investigating the Effects of Cuing Medication Availability on Patient-controlled Analgesia Pump Usage in Pediatric Patients: Results of a Randomized Controlled Trial.

Clin J Pain 2021 01;37(1):1-10

Department of Anesthesiology.

Objectives: The study of patient-controlled analgesia (PCA) behaviors has led to a greater understanding of factors that affect the pain experience. Although PCA behaviors can be influenced by cues to medication availability, no studies have examined the effects of such cues in pediatric populations.

Materials And Methods: This randomized controlled trial examined patient satisfaction with pain management, PCA behaviors, opioid consumption, and state anxiety in a sample of 125 postsurgical children and adolescents (7 to 17 y). Patients were randomized to a "light" group (lockout period status cued by light on the PCA button) or control group (no cues to medication availability).

Results: Although cuing did not affect patient satisfaction with pain management (P=0.11), patients in the light group consumed significantly more opioid than those in the control group (adj. P=0.016). This effect was primarily because of children in the light group (median, 0.019; interquartile range, 0.012 to 0.036 mg/kg/h) consuming more opioid than children (12 y or younger) in control group (median, 0.015; interquartile range, 0.006 to 0.025 mg/kg/h) (P=0.007). In contrast to the control group, for patients in the light group, opioid consumption was unrelated to pain and the proportion of patients with a 1:1 injections:attempts ratio was higher (P<0.001) across the study period.

Discussion: The overall pattern of results suggests that patients in the light group used their PCA in response to the light more than in response to their pain, which likely reflects operant influences on PCA behavior by pediatric patients.
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http://dx.doi.org/10.1097/AJP.0000000000000892DOI Listing
January 2021

Chemoenzymatic Total Syntheses of Artonin I with an Intermolecular Diels-Alderase.

Biotechnol J 2020 Nov 12;15(11):e2000119. Epub 2020 Oct 12.

Peking-Tsinghua Center for Life Science, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, P. R. China.

Diels-Alder reaction is one of the most important transformations used in organic synthesis, with the ability to construct two new CC bonds and up to four chiral centers simultaneously. However, the biggest synthetic challenge in Diels-Alder reaction lies in controlling its regio-, diastereo-, and enantioselectivity. Using Stille cross-coupling and enzymatic Diels-Alder reaction as the key steps, the first chemoenzymatic total synthesis of artonin I is achieved in 30% overall yield over only seven steps. This enzymatic Diels-Alder reaction catalyzed by MaDA is featured with excellent endo- and enantioselectivity and high catalytic efficiency (k /K = 362 ± 54 mm  s ). These successful chemoenzymatic total syntheses of artonin I and dideoxyartonin I demonstrated the remarkable potential of the intermolecular Diels-Alderase MaDA in biocatalysis.
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http://dx.doi.org/10.1002/biot.202000119DOI Listing
November 2020

Increased levels of HE4 (WFDC2) in systemic sclerosis: a novel biomarker reflecting interstitial lung disease severity?

Ther Adv Chronic Dis 2020 12;11:2040622320956420. Epub 2020 Sep 12.

Department of Laboratory medicine, Shanxi Bethune Hospital, Shanxi Province, China.

Background: Human epididymis protein 4 (HE4, also known as WFDC-2) has been implicated in fibrotic disorders pathobiology. We tested the hypothesis that HE4 may be used as a candidate biomarker for systemic sclerosis (SSc)-related interstitial lung disease (SSc-ILD).

Methods: A total of 169 consecutive SSc patients and 169 age-and sex-matched healthy controls were enrolled and blood samples were collected. Pulmonary function tests (PFTs) and paired lavage was performed on 169 patients and 37 healthy controls. All patients were classified as having SSc-no ILD or SSc-ILD, based on high-resolution computed tomography (CT) scans of the chest, and a semiquantitative grade of ILD extent was evaluated through CT scans (grade 1, 0-25%; grade 2, 26-50%; grade 3, 51-75%; grade 4, 76-100%). Serum and bronchoalveolar lavage fluid (BALF) HE4 levels were measured by enzyme-linked immunosorbent assay.

Results: Serum HE4 levels were higher in SSc patients [median (interquartile range), 139.4 (85.9-181.8) pmol/l] compared with healthy controls [39.5 (24.3-54.2) pmol/l,  < 0.001] and were higher in patients with SSc-ILD [172.1 (94.8-263.3) pmol/l] than in those with SSc-no ILD [97.4 (85.5-156.5) pmol/l,  < 0.001]. This observation was replicated in the BALF samples. Corresponding values were 510.8 (144.6-1013.8) pmol/l for SSc cohort, 754.4 (299-1060) pmol/l for SSc-ILD, 555.1 (203.7-776.2) pmol/l for SSc-no ILD, and 238.7 (97.7-397.6) pmol/l for controls. The semiquantitative grade of ILD on CT scan was significantly proportional to the HE4 levels and the lung function parameter (i.e., FVC) had a negative correlation with the HE4 levels.

Conclusion: This is the first study to demonstrate the potential clinical utility of blood and BALF HE4 as a biomarker for SSc-ILD. Future prospective validation studies are warranted.
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http://dx.doi.org/10.1177/2040622320956420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488885PMC
September 2020

Vitamin D3 analogue facilitates epithelial wound healing through promoting epithelial-mesenchymal transition via the Hippo pathway.

J Dermatol Sci 2020 Nov 7;100(2):120-128. Epub 2020 Sep 7.

Department of Dermatology, the Fifth Affiliated Hospital, Southern Medical University, Guangzhou, China. Electronic address:

Background: Wound healing is a complex physiological process that is crucial for reestablishing the epithelial barrier following injury.

Objective: The aim of this study was to demonstrate the efficacy of calcipotriol, a synthetic vitamin D3 analogue, in wound healing in an acute mice wound model.

Methods: An excision wound model was established in mice, and the wound healing activity of calcipotriol was evaluated. Human keratinocyte cell lines, HaCaT and NHEK, were utilized in in vitro skin wound healing model. Cytokine expression levels were measured by real-time PCR and ELISA assay. The expression of epithelial-mesenchymal transition (EMT)-associated molecules and the phosphorylation of Yes-associated protein (YAP) was determined by western blotting.

Results: The increase in re-epithelialization by calcipotriol treatment early in the wound was associated with the EMT process. A scratch assay using HaCaT and NHEK cells also showed that calcipotriol administration resulted in effective wound closure. We demonstrated that calcipotriol promoted keratinocyte migration by interfering with the Hippo pathway. Calcipotriol-mediated enhancement of cell migration is related to downregulated phosphorylation of YAP and increased levels of YAP and PDZ-binding motif (TAZ). Mechanistically, we defined that calcipotriol facilitated the crosstalk between the YAP/TAZ and TGF-β/Smad signaling pathways, eliciting EMT in keratinocytes during the wound healing process.

Conclusions: These results suggest that the positive effect of calcipotriol on keratinocyte migration is mediated by the induction of EMT via the regulation of Hippo pathway, which promotes the acceleration of wound closure.
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http://dx.doi.org/10.1016/j.jdermsci.2020.08.015DOI Listing
November 2020