Publications by authors named "Ling Zhu"

714 Publications

Signal-on photoelectrochemical immunoassay mediated by the etching reaction of oxygen/phosphorus co-doped g-CN/AgBr/MnO nanohybrids.

Anal Chim Acta 2021 Aug 24;1171:338680. Epub 2021 May 24.

Key Laboratory for Analytical Science of Food Safety and Biology (MOE & Fujian Province), State Key Laboratory of Photocatalysis on Energy and Environment, Department of Chemistry, Fuzhou University, Fuzhou, 350108, People's Republic of China. Electronic address:

We designed a signal-on photoelectrochemical (PEC) immunoassay for the sensitive monitoring of prostate-specific antigen (PSA) based on the etching reaction of hydrogen peroxide (HO) toward oxygen/phosphorus co-doped graphitic CN/AgBr/MnO nanosheets (OP-g-CN/AgBr/MnO). Initially, glucose oxidase (GO)-labeled detection antibodies were introduced into the capture antibody-coated microplate with a sandwich-type immunoreaction in the presence of PSA. Then, the as-generated HO from the decomposition of glucose by GO etched the manganese dioxide (MnO) nanosheets into manganese ions (Mn), thereby causing the exposure of the underlying OP-g-CN/AgBr. Meanwhile, HO could be also used as an electron scavenger, and restrain the recombination of the electron-hole pairs of OP-g-CN/AgBr. Two advantages of HO enhanced the photocurrent synergistically. Under optimum conditions, the PEC immunoassay showed high sensitivity toward target PSA within a dynamic working range of 0.05-50 ng mL with a limit of detection of 17 pg mL. In addition, our system possessed high specificity, favorable selectivity, and good stability. Relative to commercialized PSA ELISA kits, the accuracy of our strategy was acceptable. More importantly, our strategy can be easily extended to screen other biomarkers by controlling the corresponding antibodies.
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http://dx.doi.org/10.1016/j.aca.2021.338680DOI Listing
August 2021

An autoregulatory negative feedback loop controls thermomorphogenesis in Arabidopsis.

PLoS Genet 2021 Jun 1;17(6):e1009595. Epub 2021 Jun 1.

Department of Molecular Biosciences and The Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, Texas, United States of America.

Plant growth and development are acutely sensitive to high ambient temperature caused in part due to climate change. However, the mechanism of high ambient temperature signaling is not well defined. Here, we show that HECATEs (HEC1 and HEC2), two helix-loop-helix transcription factors, inhibit thermomorphogenesis. While the expression of HEC1 and HEC2 is increased and HEC2 protein is stabilized at high ambient temperature, hec1hec2 double mutant showed exaggerated thermomorphogenesis. Analyses of the four PHYTOCHROME INTERACTING FACTOR (PIF1, PIF3, PIF4 and PIF5) mutants and overexpression lines showed that they all contribute to promote thermomorphogenesis. Furthermore, genetic analysis showed that pifQ is epistatic to hec1hec2. HECs and PIFs oppositely control the expression of many genes in response to high ambient temperature. PIFs activate the expression of HECs in response to high ambient temperature. HEC2 in turn interacts with PIF4 both in yeast and in vivo. In the absence of HECs, PIF4 binding to its own promoter as well as the target gene promoters was enhanced, indicating that HECs control PIF4 activity via heterodimerization. Overall, these data suggest that PIF4-HEC forms an autoregulatory composite negative feedback loop that controls growth genes to modulate thermomorphogenesis.
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http://dx.doi.org/10.1371/journal.pgen.1009595DOI Listing
June 2021

Structural basis for neutralization of an anicteric hepatitis associated echovirus by a potent neutralizing antibody.

Cell Discov 2021 May 25;7(1):35. Epub 2021 May 25.

CAS Key Laboratory of Infection and Immunity, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.

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http://dx.doi.org/10.1038/s41421-021-00264-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149713PMC
May 2021

Icarrin prevents cardiomyocyte apoptosis in spontaneously hypertensive rats by inhibiting endoplasmic reticulum stress pathways.

J Pharm Pharmacol 2021 May 21. Epub 2021 May 21.

Key Laboratory of Basic Pharmacology of Ministry of Education, Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou, China.

Objectives: This study aimed to explore whether icarrin (ICA) can protect cardiomyocytes from hypertension-induced damage by inhibiting endoplasmic reticulum stress (ERS).

Methods: Spontaneously hypertensive rats (SHRs) were orally administered water or ICA at 10, 20 and 40 mg/kg once daily for 12 weeks, and Wistar-Kyoto (WKY) rats were used as control. Changes in the growth and blood pressure of rats were assessed. Cardiac function was determined by ultrasound and the left ventricle mass was calculated. Myocardial tissue structure was assessed by haematoxylin and eosin staining, cardiomyocyte apoptosis was observed by TUNEL staining and the expression of ERS-related proteins was determined by western blotting.

Results: In the SHR group, blood pressure was significantly high, left ventricular function decreased and left ventricular mass index increased. Additionally, left ventricular cardiomyocyte hypertrophy, disordered myofilament arrangement and increased cardiomyocyte apoptosis were observed by histological staining. ERS-induced proteins associated with apoptosis, including GRP78, PERK, ATF-6, ATF-4, CHOP, DR5, Caspase 12, c-JUN and ASK-1 were found to be highly expressed. ICA treatment reduced blood pressure and regulated the expression of proteins induced by ERS. Cardiomyocyte apoptosis decreased and left ventricular function improved.

Conclusions: ICA can inhibit ERS-induced apoptosis of cardiomyocytes and protect ventricular function in SHR.
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http://dx.doi.org/10.1093/jpp/rgaa016DOI Listing
May 2021

Osthole improves pulmonary artery hypertension by inducing apoptosis in pulmonary artery smooth muscle cells.

J Pharm Pharmacol 2021 May 14. Epub 2021 May 14.

Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Key Laboratory of Basic Pharmacology of Guizhou Province, Department of Pharmacology, School of Pharmacy, Zunyi Medical University, Zunyi, Guizhou, China.

Objectives: The objectives of this study were to explore the effect of Osthole (Ost) on apoptosis in pulmonary artery smooth muscle cells (PASMCs) and investigate the potential mechanism of this effect.

Methods: Rats were injected subcutaneously with monocrotaline (MCT) to establish a PAH model, and Ost were intragastrically administrated from day 1 to day 35. After 35 days administration, the mean pulmonary artery pressure and lung weight index were measured. HE and TUNEL staining were used to observe the morphology of pulmonary artery and the apoptosis of PASMCs. In addition, the apoptosis of PASMCs were detected by flow cytometry in cultured PASMCs. The proteins of Bax and Bcl-2, and the levels of p-ASK1 and cleaved caspase 3 were measured by Western blot.

Key Findings: Ost decreased the mean pulmonary artery pressure and lung weight index in MCT-induced rats, and promoted apoptosis in PASMCs in MCT-induced rats and PDGF-BB stimulated PASMCs. Ost increased the ratio of Bax/Bcl-2 and the levels of p-ASK1, cleaved caspase 3 in MCT-induced rats and PDGF-BB stimulated PASMCs.

Conclusion: Ost promoted apoptosis in PASMCs in vivo and in vitro, and the mechanism may be associated with upregulation of ASK1 and the Bax/Bcl-2-caspase 3 signalling pathway.
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http://dx.doi.org/10.1093/jpp/rgab068DOI Listing
May 2021

Epidemiology, species distribution, and outcome of nosocomial Candida spp. bloodstream infection in Shanghai: an 11-year retrospective analysis in a tertiary care hospital.

Ann Clin Microbiol Antimicrob 2021 May 13;20(1):34. Epub 2021 May 13.

Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.

Background: The incidence of Candida bloodstream infections (BSIs), has increased over time. In this study, we aimed to describe the current epidemiology of Candida BSI in a large tertiary care hospital in Shanghai and to determine the risk factors of 28-day mortality and the impact of antifungal therapy on clinical outcomes.

Methods: All consecutive adult inpatients with Candida BSI at Ruijin Hospital between January 1, 2008, and December 31, 2018, were enrolled. Underlying diseases, clinical severity, species distribution, antifungal therapy, and their impact on the outcomes were analyzed.

Results: Among the 370 inpatients with 393 consecutive episodes of Candida BSI, the incidence of nosocomial Candida BSI was 0.39 episodes/1000 hospitalized patients. Of the 393 cases, 299 (76.1%) were treated with antifungal therapy (247 and 52 were treated with early appropriate and targeted antifungal therapy, respectively). The overall 28-day mortality rate was 28.5%, which was significantly lower in those who received early appropriate (25.5%) or targeted (23.1%) antifungal therapy than in those who did not (39.4%; P = 0.012 and P = 0.046, respectively). In multivariate Cox regression analysis, age, chronic renal failure, mechanical ventilation, and severe neutropenia were found to be independent risk factors of the 28-day mortality rate. Patients who received antifungal therapy had a lower mortality risk than did those who did not.

Conclusions: The incidence of Candida BSI has increased steadily in the past 11 years at our tertiary care hospital in Shanghai. Antifungal therapy influenced short-term survival, but no significant difference in mortality was observed between patients who received early appropriate and targeted antifungal therapy.
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http://dx.doi.org/10.1186/s12941-021-00441-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120712PMC
May 2021

[Novel understanding of "acupuncture being for reducing rather than reinforcing": an analysis based on perspective and position].

Authors:
Feng Yang Ling Zhu

Zhongguo Zhen Jiu 2021 Apr;41(4):462-6

Institue of Information on Traditional Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China.

"Acupuncture being for reducing rather than reinforcing" is originated from the description in ( ) of the Ming dynasty. The understanding and evaluation of it by later physicians are generally limited to the knowledge system of acupuncture-moxibustion theory. Through the investigation from the context of the original text, the context of the original book, medical background and academic origin, the authors propose that this original phrase should be understood in view of novel perspective and position. From a larger perspective, it is necessary to base on the classification of excess or deficiency of disorders by the medical masters of the Jin and Yuan dynasties and the understanding of reinforcing and reducing techniques accordingly. In view of a relatively specific point, the influence of relevant academic knowledge of and in the related medical works should be also considered. It is suggested that the understanding of some judgments or propositions in ancient acupuncture-moxibustion theory should not be limited to the scope of knowledge system of the theory, but need to give the consideration and analysis from the full dimensions of traditional Chinese medicine.
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http://dx.doi.org/10.13703/j.0255-2930.20200429-k0005DOI Listing
April 2021

Publisher Correction: SARS-CoV-2 spike protein interacts with and activates TLR4.

Cell Res 2021 Apr 27. Epub 2021 Apr 27.

Institute of Systems Biomedicine, Department of Immunology, School of Basic Medical Sciences, Beijing Key Laboratory of Tumor Systems Biology, Peking University Health Science Center, Beijing, 100191, China.

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http://dx.doi.org/10.1038/s41422-021-00501-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077189PMC
April 2021

[Clinical application of self-made minimally invasive hood-assisted transforaminal lumbar interbody fusion via modified bilateral Wiltse approach in the treatment of lumbar degenerative diseases].

Zhongguo Gu Shang 2021 Apr;34(4):297-303

Hubei 672 Integrated Chinese and Western Medicine Orthopaedics Hospital, Wuhan 430000, Hubei, China.

Objective: To explore the advantages of self made minimally invasive hook assisted transforaminal lumbar interbody fusion (TLIF) via modified bilateral Wiltse approach in the treatment of lumbar degenerative diseases.

Methods: The clinical data of 140 patients underwent lumbar spine fusion surgery from October 2016 to October 2017 were retrospectively analyzed. Among them, 72 cases were treated by self-made minimally invasive hook-assisted TLIF via modified bilateral Wiltse approach (group A), there were 37 males and 35 females, aged (48±16) years old;68 cases were treated by TLIF via traditional posterior median approach (group B ), there were 38 males and 30 females, aged (45±15) years old. The surgical incision size, operation time, intraoperative blood loss volume, postoperative drainage volume, postoperative wound healing, and intervertebral fusion rate at the final follow-up were recorded between two groups. Visual analogue scale (VAS) and Oswestry Disability Index (ODI) were used to assess the clinical efficacy.

Results: All the patients were followed up for 3 to 13 (8±5) months. The wound in group A healed well after operation, and 1 case in group B occurred wound necrosis after operation, and healed after debridement and suture. There were no significant differences in operation time and postoperative fusion rate between two surgical methods (>0.05). Group A had obvious advantages in surgical incision size, intraoperative blood loss volume and postoperative drainage volume (<0.05), and the postoperative VAS score of low back pain and ODI were better than group B (<0.05).

Conclusion: The self made minimally invasive hook assistedTLIF via modified bilateral Wiltse approach has the characteristics of minimally invasive, less intraoperative blood loss, less postoperative drainage, fewer complications, and more stable fusion in the treatment of lumbar degenerative desease.
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http://dx.doi.org/10.12200/j.issn.1003-0034.2021.04.002DOI Listing
April 2021

Procyanidin B2 and rutin in Ginkgo biloba extracts protect human retinal pigment epithelial (RPE) cells from oxidative stress by modulating Nrf2 and Erk1/2 signalling.

Exp Eye Res 2021 Jun 20;207:108586. Epub 2021 Apr 20.

The University of Sydney, Sydney Pharmacy School, Faculty of Medicine and Health NSW, 2006, Australia. Electronic address:

Oxidative stress plays an important role in the pathogenesis of human retinal diseases. Ginkgo biloba products are widely consumed herbal supplements that contain ingredients with anti-oxidant potentials. However, the active agents in ginkgo biloba extracts (GBE) are unclear. This study assessed the anti-oxidant effects of 19 natural compounds isolated from GBE to provide a rational basis for their use in preventing retinal diseases. The compounds were tested in retinal pigment epithelial (RPE) cells subjected to tert-butyl hydroperoxide (t-BHP)-induced oxidative stress. Cell viability and intracellular reactive oxygen species (ROS) were assessed and flow cytometry was used to delineate the cell death profile. The expression of nuclear factor erythroid 2-related factor-2 (Nrf2) was activated in RPE cells by t-BHP accompanied with an activation of Erk1/2 signaling. GBE-derived rutin and procyanidin B2 ameliorated t-BHP-induced cell death and promoted cell viability by suppressing intracellular ROS generation. These agents also enhanced Nrf2 expression with activating Erk1/2 signaling in RPE cells. In contrast, the other compounds tested were minimally active and did not prevent the loss of cell viability elicited by t-BHP. The present findings suggest that rutin and procyanidin B2 may have potential therapeutic values in the prevention of retinal diseases induced by oxidative damage.
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http://dx.doi.org/10.1016/j.exer.2021.108586DOI Listing
June 2021

Nicorandil attenuates high glucose-induced insulin resistance by suppressing oxidative stress-mediated ER stress PERK signaling pathway.

BMJ Open Diabetes Res Care 2021 Apr;9(1)

Department of Cardiology, Affiliated Shaanxi Provincial People's Hospital, Northwestern Polytechnical University, Xi'an, China

Introduction: Glucose-induced insulin resistance is a typical character of diabetes. Nicorandil is now widely used in ischemic heart disease. Nicorandil shows protective effects against oxidative and endoplasmic reticulum (ER) stress, which are involved in insulin resistance. Here, we investigated mechanisms of nicorandil's novel pharmacological activity on insulin resistance in diabetes.

Research Design And Methods: Nicorandil was administrated to streptozotocin-induced animals with diabetes and high glucose exposed skeletal muscle cells. Insulin resistance and glucose tolerance were evaluated. Molecular mechanisms concerning oxidative stress, ER stress signaling activation and glucose uptake were assessed.

Results: Nicorandil attenuated high glucose-induced insulin resistance without affecting fasting blood glucose and glucose tolerance in whole body and skeletal muscle in rats with diabetes. Nicorandil treatment suppressed protein kinase C/nicotinamide adenine dinucleotide phosphate oxidases system activities by reducing cytoplasmic free calcium level in skeletal muscle cells exposed to high glucose. As a result, the oxidative stress-mediated ER stress protein kinase RNA-like endoplasmic reticulum kinase (PERK)/eukaryotic initiation factor 2α/activating transcription factor 4/CEBP homologous protein/tribbles homolog (TRB)3 signaling pathway activation was inhibited. Nicorandil downregulated expression of TRB3 and thus facilitated Akt phosphorylation in response to insulin stimulation, leading to glucose transporter4 plasma membrane translocation which promoted glucose uptake capability of skeletal muscle cells.

Conclusions: By reducing cytoplasmic calcium, nicorandil alleviated high glucose-induced insulin resistance by inhibiting oxidative stress-mediated ER stress PERK pathway.
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http://dx.doi.org/10.1136/bmjdrc-2020-001884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070885PMC
April 2021

Remifentanil preconditioning promotes liver regeneration via upregulation of β-arrestin 2/ERK/cyclin D1 pathway.

Biochem Biophys Res Commun 2021 Jun 13;557:69-76. Epub 2021 Apr 13.

Department of Anesthesiology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, China. Electronic address:

Remifentanil is a potent, short-acting opioid analgesic drug that can protect tissues from ischemia and reperfusion injury though anti-inflammatory effects. However, the utility of remifentanil in liver regeneration after hepatectomy is not known. Using a 70% hepatectomy mouse model (PHx), we found that preconditioning animals with 4 μg/kg remifentanil enhanced liver regeneration through supporting hepatocyte proliferation but not through anti-inflammatory effects. These effects were also phenocopied in vitro where 40 mM remifentanil promoted the proliferation of primary mouse hepatocyte cultures. We further identified that remifentanil treatment increased the expression of β-arrestin 2 in vivo and in vitro. Demonstrating specificity, remifentanil preconditioning failed to promote liver regeneration in liver-specific β-arrestin 2 knockout (CKO) mice subjected to PHx. While remifentanil increased the expression of activated (phosphorylated)-ERK and cyclin D1 in PHx livers, their levels were not significantly changed in remifentanil-treated CKO mice nor in WT mice pretreated with the ERK inhibitor U0126. Our findings suggest that remifentanil promotes liver regeneration via upregulation of a β-arrestin 2/ERK/cyclin D1 axis, with implications for improving regeneration process after hepatectomy.
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http://dx.doi.org/10.1016/j.bbrc.2021.04.008DOI Listing
June 2021

The role of SOCS proteins in the development of virus- induced hepatocellular carcinoma.

Virol J 2021 Apr 13;18(1):74. Epub 2021 Apr 13.

Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu City, 611130, Sichuan, People's Republic of China.

Background: Liver cancer has become one of the most common cancers and has a high mortality rate. Hepatocellular carcinoma is one of the most common liver cancers, and its occurrence and development process are associated with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. Main body The serious consequences of chronic hepatitis virus infections are related to the viral invasion strategy. Furthermore, the viral escape mechanism has evolved during long-term struggles with the host. Studies have increasingly shown that suppressor of cytokine signaling (SOCS) proteins participate in the viral escape process. SOCS proteins play an important role in regulating cytokine signaling, particularly the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway. Cytokines stimulate the expression of SOCS proteins, in turn, SOCS proteins inhibit cytokine signaling by blocking the JAK-STAT signaling pathway, thereby achieving homeostasis. By utilizing SOCS proteins, chronic hepatitis virus infection may destroy the host's antiviral responses to achieve persistent infection.

Conclusions: This review provides recent knowledge regarding the role of SOCS proteins during chronic hepatitis virus infection and provides some new ideas for the future treatment of chronic hepatitis.
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http://dx.doi.org/10.1186/s12985-021-01544-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045357PMC
April 2021

MicroRNA-30 regulates left ventricular hypertrophy in chronic kidney disease.

JCI Insight 2021 May 24;6(10). Epub 2021 May 24.

National Clinical Research Center of Kidney Diseases, and.

Left ventricular hypertrophy (LVH) is a primary feature of cardiovascular complications in patients with chronic kidney disease (CKD). miRNA-30 is an important posttranscriptional regulator of LVH, but it is unknown whether miRNA-30 participates in the process of CKD-induced LVH. In the present study, we found that CKD not only resulted in LVH but also suppressed miRNA-30 expression in the myocardium. Rescue of cardiomyocyte-specific miRNA-30 attenuated LVH in CKD rats without altering CKD progression. Importantly, in vivo and in vitro knockdown of miRNA-30 in cardiomyocytes led to cardiomyocyte hypertrophy by upregulating the calcineurin signaling directly. Furthermore, CKD-related detrimental factors, such as fibroblast growth factor-23, uremic toxin, angiotensin II, and transforming growth factor-β, suppressed cardiac miRNA-30 expression, while miRNA-30 supplementation blunted cardiomyocyte hypertrophy induced by such factors. These results uncover a potentially novel mechanism of CKD-induced LVH and provide a potential therapeutic target for CKD patients with LVH.
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http://dx.doi.org/10.1172/jci.insight.138027DOI Listing
May 2021

Effect of selectively knocking down key metabolic genes in Müller glia on photoreceptor health.

Glia 2021 Aug 9;69(8):1966-1986. Epub 2021 Apr 9.

Discipline of Ophthalmology, Sydney Medical School, The University of Sydney, Save Sight Institute, Sydney, New South Wales, Australia.

The importance of Müller glia for retinal homeostasis suggests that they may have vulnerabilities that lead to retinal disease. Here, we studied the effect of selectively knocking down key metabolic genes in Müller glia on photoreceptor health. Immunostaining indicated that murine Müller glia expressed insulin receptor (IR), hexokinase 2 (HK2) and phosphoglycerate dehydrogenase (PHGDH) but very little pyruvate dehydrogenase E1 alpha 1 (PDH-E1α) and lactate dehydrogenase A (LDH-A). We crossed Müller glial cell-CreER (MC-CreER) mice with transgenic mice carrying a floxed IR, HK2, PDH-E1α, LDH-A, or PHGDH gene to study the effect of selectively knocking down key metabolic genes in Müller glia cells on retinal health. Selectively knocking down IR, HK2, or PHGDH led to photoreceptor degeneration and reduced electroretinographic responses. Supplementing exogenous l-serine prevented photoreceptor degeneration and improved retinal function in MC-PHGDH knockdown mice. We unexpectedly found that the levels of retinal serine and glycine were not reduced but, on the contrary, highly increased in MC-PHGDH knockdown mice. Moreover, dietary serine supplementation, while rescuing the retinal phenotypes caused by genetic deletion of PHGDH in Müller glial cells, restored retinal serine and glycine homeostasis probably through regulation of serine transport. No retinal abnormalities were observed in MC-CreER mice crossed with PDH-E1α- or LDH-A-floxed mice despite Cre expression. Our findings suggest that Müller glia do not complete glycolysis but use glucose to produce serine to support photoreceptors. Supplementation with exogenous serine is effective in preventing photoreceptor degeneration caused by PHGDH deficiency in Müller glia.
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http://dx.doi.org/10.1002/glia.24005DOI Listing
August 2021

LITAF acts as a novel regulator for pathological cardiac hypertrophy.

J Mol Cell Cardiol 2021 Apr 3;156:82-94. Epub 2021 Apr 3.

Department of Cardiology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, China. Electronic address:

Pathological hypertrophy generally progresses to heart failure. Exploring effective and promising therapeutic targets might lead to progress in preventing its detrimental outcomes. Our current knowledge about lipopolysaccharide-induced tumor necrosis factor-α factor (LITAF) is mainly limited to regulate inflammation. However, the role of LITAF in other settings that are not that relevant to inflammation, such as cardiac remodeling and heart failure, remains largely unknown. In the present study, we found that the expression of LITAF decreased in hypertrophic hearts and cardiomyocytes. Meanwhile, LITAF protected cultured neonatal rat cardiomyocytes against phenylephrine-induced hypertrophy. Moreover, using LITAF knockout mice, we demonstrated that LITAF deficiency exacerbated cardiac hypertrophy and fibrosis compared with wild-type mice. Mechanistically, LITAF directly binds to the N-terminal of ASK1, thus disrupting the dimerization of ASK1 and blocking ASK1 activation, ultimately inhibiting ASK1-JNK/p38 signaling over-activation and protecting against cardiac hypertrophy. Furthermore, AAV9-mediated LITAF overexpression attenuated cardiac hypertrophy in vivo. Conclusions: Our findings uncover the novel role of LITAF as a negative regulator of cardiac remodeling. Targeting the interaction between LITAF and ASK1 could be a promising therapeutic strategy for pathological cardiac remodeling.
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http://dx.doi.org/10.1016/j.yjmcc.2021.03.012DOI Listing
April 2021

The Potential Application of Pentacyclic Triterpenoids in the Prevention and Treatment of Retinal Diseases.

Planta Med 2021 Mar 24. Epub 2021 Mar 24.

Sydney Pharmacy School, The University of Sydney, Camperdown, Australia.

Retinal diseases are a leading cause of impaired vision and blindness but some lack effective treatments. New therapies are required urgently to better manage retinal diseases. Natural pentacyclic triterpenoids and their derivatives have a wide range of activities, including antioxidative, anti-inflammatory, cytoprotective, neuroprotective, and antiangiogenic properties. Pentacyclic triterpenoids have great potential in preventing and/or treating retinal pathologies. The pharmacological effects of pentacyclic triterpenoids are often mediated through the modulation of signalling pathways, including nuclear factor erythroid-2 related factor 2, high-mobility group box protein 1, 11-hydroxysteroid dehydrogenase type 1, and Src homology region 2 domain-containing phosphatase-1. This review summarizes recent and evidence for the pharmacological potential of pentacyclic triterpenoids in the prevention and treatment of retinal diseases. The present literature supports the further development of pentacyclic triterpenoids. Future research should now attempt to improve the efficacy and pharmacokinetic behaviour of the agents, possibly by the use of medicinal chemistry and targeted drug delivery strategies.
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http://dx.doi.org/10.1055/a-1377-2596DOI Listing
March 2021

Genetic characterization of a novel porcine reproductive and respiratory syndrome virus type I strain from southwest China.

Arch Virol 2021 Jun 24;166(6):1769-1773. Epub 2021 Mar 24.

College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China.

Porcine reproductive and respiratory syndrome (PRRS) is one of the most economically devastating viral diseases in the global pig industry. Recently, we isolated and plaque-purified porcine reproductive and respiratory syndrome virus (PRRSV) strain SC2020-1 from "aborted piglets" on a farm in Sichuan, China. To investigate the molecular biological characteristics of this strain, it was subjected to genome sequencing and analysis. The full-length genome sequence of strain SC2020-1 was 87.7% identical to that of the Lelystad strain (PRRSV type I protoype strain) and 82.2-84.8% identical to PRRSV type I isolates from China. NSP2, ORF3, and ORF4 were the most variable regions and contained discontinuous deletions or insertions when compared to other PRRSV type I strains. Phylogenetic analysis of the complete genome sequence showed that SC2020-1 clustered with PRRSV type I but outside of the three previously described branches (Lelystad virus-like, Amervac PRRS-like, and BJEU06-1-like). The Nsp2 gene was in the same branch with EUGDHD strains from China. This is the first report of PRRSV type I infection associated with abortion in sows in southwest China. Close attention should be paid to the prevention and control of this evolving virus.
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http://dx.doi.org/10.1007/s00705-021-04998-zDOI Listing
June 2021

SARS-CoV-2 spike protein interacts with and activates TLR41.

Cell Res 2021 Mar 19. Epub 2021 Mar 19.

Institute of Systems Biomedicine, Department of Immunology, School of Basic Medical Sciences, Beijing Key Laboratory of Tumor Systems Biology, Peking University Health Science Center, Beijing, 10019, China.

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http://dx.doi.org/10.1038/s41422-021-00495-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7975240PMC
March 2021

Design of amino-functionalized hollow mesoporous silica cube for enzyme immobilization and its application in synthesis of phosphatidylserine.

Colloids Surf B Biointerfaces 2021 Jun 1;202:111668. Epub 2021 Mar 1.

National Engineering Research Center for Functional Food, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, School of Food Science and Technology, Jiangnan University, 1800 Lihu Road, Wuxi, 214122, China. Electronic address:

In this study, hollow mesoporous silica cube (HMSC) modified with amino (-NH) were synthesized and applied in the immobilization of phospholipase D (PLD) via physical adsorption and chemical cross-linking strategy. The amino-functionalized nano carrier HMSC represented excellent immobilization ability and achieved 87.15 % immobilization rate. The immobilized PLD has wider pH application range and thermal stability, and maintained over 90% of the initial activity after incubation at 50 °C for 2 h. After 50 days of storage at 4 ℃, immobilized PLD retained 40.12 % of its initial activity while free PLD lost 88.28% of its initial activity. The modified HMSC with immobilized PLD (HMSC-NH-PLD) retained 50.73% activities after 9 consecutive reuses. Using the HMSC-NH-PLD, a high-efficient method for the conversion of phosphatidylserine (PS) from phosphatidylcholine (PC) and L-serine was proposed. The HMSC-NH-PLD exhibited prominent enzymatic activity for PS synthesis, the maximal conversion of PS was 90.40% with a catalytic efficiency (CE) of 31.95 μmol / (g h under the optimal conditions. The research in this paper provides a sustainable and efficient biocatalysis application for PS synthesis.
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http://dx.doi.org/10.1016/j.colsurfb.2021.111668DOI Listing
June 2021

Clinicopathological aspects of primary mucosa-associated lymphoid tissue lymphoma of the salivary gland: A retrospective single-center analysis of 72 cases.

J Oral Pathol Med 2021 Mar 17. Epub 2021 Mar 17.

Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Department of Oral Pathology, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Disease, Shanghai Ninth People's Hospital, Shanghai, China.

Background: Salivary gland extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue lymphoma (MALT lymphoma) is uncommon and has not been studied extensively. We aimed to investigate the features of clinicopathological and molecular changes of salivary MALT lymphoma.

Methods: Seventy-two cases of primary salivary MALT lymphoma that had clinicopathological information available were utilized in this study. MALT1 gene translocation, trisomy 3, and trisomy 18 were detected by interphase fluorescence in situ hybridization (FISH). The data were analyzed using SPSS 17.0 software package.

Results: The ratio of male to female was 1:2.8, and the median age was 57.0 years. 12.5% (9/72) of the patients presented with multiple swellings. Among the others with solitary mass, the parotid gland was involved most frequently (47/63,74.6%), followed by the palate (7/63, 11.1%). 34.7% of patients had an autoimmune disease, with Sjögren syndrome (SS) being the most common. Among the 70 cases successfully performed, it was identified that trisomy 3 was the most frequent molecular change (41/70, 58.6%), followed by trisomy 18 (7/70, 10%) and MALT1 translocation (5/70, 7.1%). The tumor tissue tended to exhibit trisomy 3 in patients without SS (p = 0.038). The 5-year overall survival was 94.1%, and the 5-year disease-free survival was 85.3% (mean follow-up time: 104.7 months). The patients without SS and trisomy 18 had a prolonged recurrence-free survival (p = 0.015, p = 0.001 respectively).

Conclusion: Salivary gland MALT lymphoma is associated with autoimmune diseases, and trisomy 3 is the most common genetic change. Trisomy 18 can be used to predict the possibility of tumor relapse.
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http://dx.doi.org/10.1111/jop.13168DOI Listing
March 2021

A rare case of complete uniparental isodisomy of chromosome 2 with no phenotypic abnormalities.

Taiwan J Obstet Gynecol 2021 03;60(2):378-379

Department of Clinical Laboratory, Maternal and Child Health Hospital of Hubei Province, Wuhan, Hubei, PR China. Electronic address:

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http://dx.doi.org/10.1016/j.tjog.2021.01.024DOI Listing
March 2021

A rare case of uniparental isodisomy of chromosome 19 with no phenotypic abnormalities.

Taiwan J Obstet Gynecol 2021 03;60(2):376-377

Department of Clinical Laboratory, Maternal and Child Health Hospital of Hubei Province, Wuhan, Hubei, PR China. Electronic address:

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http://dx.doi.org/10.1016/j.tjog.2021.01.023DOI Listing
March 2021

Surfactant-assisted thermal hydrolysis off waste activated sludge for improved dewaterability, organic release, and volatile fatty acid production.

Waste Manag 2021 Apr 1;124:339-347. Epub 2021 Mar 1.

Shenzhen Environmental Science and New Energy Laboratory, Tsinghua-Berkeley Shenzhen Institute, Tsinghua University, Shenzhen, China; Shenzhen Engineering Research Laboratory for Sludge and Food Waste Treatment and Resource Recovery, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, China; Guangdong Provincial Engineering Research Centre for Urban Water Recycling and Environmental Safety, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, China; Environmental Engineering Research Centre, Department of Civil Engineering, The University of Hong Kong, Pokfulam, Hong Kong, China. Electronic address:

The surfactant-assisted thermal hydrolysis pretreatment (THP) of waste activated sludge (WAS) was investigated, focusing on the effect of the surfactant addition on the results of sludge disintegration, dewaterability, organic release, and production of volatile fatty acids (VFAs) via fermentation. Typical anionic surfactant sodium dodecyl sulfate (SDS) and cationic surfactant cetyl trimethyl ammonium bromide (CTAB) were used for the THP experiments. The supernatant of the THP-treated sludge was anaerobically fermented to determine its potential VFAs yield. The results showed that the surfactant addition, particularly CTAB, enhanced the hydrolysis and organic solubilization of the sludge during THP. CTAB addition led to a 36% increase of dissolved organic and a 27% increase of VFAs production. For the THP-treated sludge with the surfactant addition, its dewaterability was also greatly improved. When the CTAB dosage increased from 0 to 0.10 g/g VSS, the minimum capillary suction time (CST) of the sludge decreased from 205 to 50 s/g TSS, and the sludge particles became smaller and less negative with the zeta potential changing from -12.4 to -8.2 mV. Analysis of extracellular polymeric substances (EPS) of the sludge revealed that the surfactant addition increased the sludge disintegration and organic dissolution during the THP process. The surfactant-assisted THP is shown to be a promising technology to enhance the WAS treatment for improved sludge dewaterability, waste reduction, and resource recovery.
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http://dx.doi.org/10.1016/j.wasman.2021.02.024DOI Listing
April 2021

Timosaponin AIII Induces G2/M Arrest and Apoptosis in Breast Cancer by Activating the ATM/Chk2 and p38 MAPK Signaling Pathways.

Front Pharmacol 2020 15;11:601468. Epub 2021 Jan 15.

Department of Natural Medicinal Chemistry, School of Chinese Pharmacy, China Pharmaceutical University, Nanjing, China.

Timosaponin AIII (TAIII), a steroidal saponin, exerts potent anti-tumor activity in various cancers, especially breast cancer. However, the concrete molecular mechanisms of TAIII against breast cancer are still unclear. Here, we find that TAIII triggers DNA damage, leads to G2/M arrest, and ultimately induces apoptosis in breast cancer both and . TAIII induced G2/M phase arrest and apoptosis in MDA-MB-231 and MCF7 cells accompanied with down-regulation of CyclinB1, Cdc2 and Cdc25C. Further data showed that the ATM/Chk2 and p38 pathways were activated representing by up-regulated levels of p-H2A.X and p-p38, which indicated an induction of DNA damage by TAIII, leading to cell cycle arrest and apoptosis. The effects of TAIII were further confirmed by employing inhibitors of ATM and p38 pathways. , TAIII suppressed the growth of subcutaneous xenograft tumor without obvious toxicity, which indicated by Ki67 and TUNEL analysis. Data also showed that TAIII stimulated the ATM/Chk2 and p38 MAPK pathways , which in consistent with the effects . Hence, our data demonstrate that TAIII triggers DNA damage and activates ATM/Chk2 and p38 MAPK pathways, and then induces G2/M phase arrest and apoptosis in breast cancer, which provide theoretical evidence for TAIII utilized as drug against breast cancer.
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http://dx.doi.org/10.3389/fphar.2020.601468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898553PMC
January 2021

Mutation of a major CG methylase alters genome-wide lncRNA expression in rice.

G3 (Bethesda) 2021 Apr;11(4)

Key Laboratory of Molecular Epigenetics of the Ministry of Education (MOE), Northeast Normal University, Changchun 130024, China.

Plant long non-coding RNAs (lncRNAs) function in diverse biological processes, and lncRNA expression is under epigenetic regulation, including by cytosine DNA methylation. However, it remains unclear whether 5-methylcytosine (5mC) plays a similar role in different sequence contexts (CG, CHG, and CHH). In this study, we characterized and compared the profiles of genome-wide lncRNA profiles (including long intergenic non-coding RNAs [lincRNAs] and long noncoding natural antisense transcripts [lncNATs]) of a null mutant of the rice DNA methyltransferase 1, OsMET1-2 (designated OsMET1-2-/-) and its isogenic wild type (OsMET1-2+/+). The En/Spm transposable element (TE) family, which was heavily methylated in OsMET1-2+/+, was transcriptionally de-repressed in OsMET1-2-/- due to genome-wide erasure of CG methylation, and this led to abundant production of specific lncRNAs. In addition, RdDM-mediated CHH hypermethylation was increased in the 5'-upstream genomic regions of lncRNAs in OsMET1-2-/-. The positive correlation between the expression of lincRNAs and that of their proximal protein-coding genes was also analyzed. Our study shows that CG methylation negatively regulates the TE-related expression of lncRNA and demonstrates that CHH methylation is also involved in the regulation of lncRNA expression.
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http://dx.doi.org/10.1093/g3journal/jkab049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049413PMC
April 2021

DEC1 deficiency results in accelerated osteopenia through enhanced DKK1 activity and attenuated PI3KCA/Akt/GSK3β signaling.

Metabolism 2021 05 17;118:154730. Epub 2021 Feb 17.

Department of Pharmacology, Nanjing Medical University, China.

Background: Human differentiated embryonic chondrocyte expressed gene 1 (DEC1) has been implicated in enhancing osteogenesis, a desirable outcome to counteract against deregulated bone formation such as retarded bone development, osteopenia and osteoporosis.

Methods And Results: DEC1 knockout (KO) and the age-matched wild-type (WT) mice were tested for the impact of DEC1 deficiency on bone development and osteopenia as a function of age. DEC1 deficiency exhibited retarded bone development at the age of 4 weeks and osteopenic phenotype in both 4- and 24-week old mice. However, the osteopenia was more severe in the 24-week age groups. Mechanistically, DEC1 deficiency downregulated the expression of bone-enhancing genes such as Runx2 and β-catenin accompanied by upregulating DKK1, an inhibitor of the Wnt/β-catenin signaling pathway. Consistently, DEC1 deficiency favored the attenuation of the integrated PI3KCA/Akt/GSK3β signaling, a pathway targeting β-catenin for degradation. Likewise, the attenuation was greater in the 24-week age group. These changes, however, were reversed by in vivo treatment with lithium chloride, a stabilizer of β-catenin, and confirmed by gain-of-function study with DEC1 transfection into DEC1 KO bone marrow mesenchymal stem cells and loss-of-function study with siDEC1 lentiviral infection into the corresponding WT cells.

Conclusion: DEC1 is a positive regulator with a broad activity spectrum in both bone development and maintenance, and the osteopenic phenotype accelerated by DEC1 deficiency is achieved by enhanced DKK1 activity and attenuated PI3KCA/Akt/GSK3β signaling.
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http://dx.doi.org/10.1016/j.metabol.2021.154730DOI Listing
May 2021

Effect of Selenium on Brain Injury in Chickens with Subacute Arsenic Poisoning.

Biol Trace Elem Res 2021 Feb 16. Epub 2021 Feb 16.

College of Veterinary Medicine, Sichuan Agricultural University, Ya'an, 625014, China.

The aim of this study was to investigate the effects of different doses of selenium (Se) on oxidative damage and neurotransmitter-related parameters in arsenic (As)-induced broiler brain tissue damage. Two hundred 1-day-old avian broilers were randomly divided into five groups and fed the following diets: control group (As 0.1 mg/kg + Se 0.2 mg/kg), As group (As 3 mg/kg + Se 0.2 mg/kg), low-Se group (As 3 mg/kg + Se 5 mg/kg), medium-Se group (As 3 mg/kg + Se 10 mg/kg), and high-Se group (As 3 mg/kg + Se 15 mg/kg). Glutathione (GSH), glutathione peroxidase (GSH-PX), nitric oxide (NO), nitric oxide synthase (NOS) activity, glutamate (Glu) concentration, glutamine synthetase (GS) activity, acetylcholinesterase (TchE) activity, and the apoptosis rate of brain cells were measured. The results showed that 3 mg/kg dietary As could induce oxidative damage and neurotransmitter disorder of brain tissue, increase the apoptosis rate of brain cells and cause damage to brain tissue, decrease activities of GSH and GSH-PX, decrease the contents of NO, decrease the activities of iNOS and tNOS, increase contents of Glu, and decrease activities of Gs and TchE. Compared with the As group, the Se addition of the low-Se and medium-Se groups protected against As-induced oxidative damage, neurotransmitter disorders, and the apoptosis rate of brain cells, with the addition of 10 mg/kg Se having the best effect. However, 15 mg/kg Se not only did not produce a protective effect against As damage but actually caused similar or severe damage.
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http://dx.doi.org/10.1007/s12011-021-02630-4DOI Listing
February 2021

Usefulness of prenatal magnetic resonance imaging in differential diagnosis of fetal congenital cystic adenomatoid malformation and bronchopulmonary sequestration.

World J Clin Cases 2021 Feb;9(4):822-829

Department of Ultrasound, Huzhou Maternity & Child Health Care Hospital, Huzhou 313000, Zhejiang Province, China.

Background: Congenital cystic adenomatoid malformation (CCAM) and bronchopulmonary sequestration (BPS) are the most common lung diseases in fetuses. There are differences in the prognosis and treatment of CCAM and BPS, and the clinical diagnosis and treatment plan is usually prepared prior to birth. Therefore, it is quite necessary to make a clear diagnosis before delivery. CCAM and BPS have similar imaging features, and the differentiation mainly relies on the difference in supply vessels. However, it is hard to distinguish them due to invisible supplying vessels on some images.

Aim: To explore the application value of magnetic resonance imaging (MRI) in the differential diagnosis of fetal CCAM and BPS.

Methods: Data analysis for 32 fetuses with CCAM and 14 with BPS diagnosed by prenatal MRI at Huzhou Maternal and Child Health Care Hospital and Anhui Provincial Children's Hospital from January 2017 to January 2020 was performed to observe the source blood vessels of lesions and their direction. Pathological confirmation was completed through CT examination and/or operations after birth.

Results: After birth, 31 cases after birth were confirmed to be CCAM, and 15 were confirmed to be BPS. The CCAM group consisted of 21 macrocystic cases and 10 microcystic cases. In 18 cases, blood vessels were visible in lesions. Blood supply of the pulmonary artery could be traced in eight cases, and in 10 cases, only vessels running from the midline to the lateral down direction were observed. No lesions were found in four macrocystic cases and one microcystic case with CCAM through CT after birth; two were misdiagnosed by MRI, and three were misdiagnosed by prenatal ultrasonography. The BPS group consisted of 12 intralobar cases and three extralobar cases. Blood vessels were visible in lesions of nine cases, in four of which, the systemic circulation blood supply could be traced, and in five of which, only vessels running from the midline to the lateral up direction were observed. Three were misdiagnosed by MRI, and four were misdiagnosed by prenatal ultrasonography.

Conclusion: CCAM and BPS can be clearly diagnosed based on the origin of blood vessels, and correct diagnosis can be made according to the difference in the direction of the blood vessels, but it is hard distinguish microcystic CCAM and BPS without supplying vessels. In some CCAM cases, mainly the macrocystic ones, the lesions may disappear after birth.
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http://dx.doi.org/10.12998/wjcc.v9.i4.822DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7852640PMC
February 2021

Double ion-exchange reaction-based photoelectrochemical immunoassay for sensitive detection of prostate-specific antigen.

Anal Chim Acta 2021 Mar 13;1149:338215. Epub 2021 Jan 13.

Key Laboratory for Analytical Science of Food Safety and Biology (MOE & Fujian Province), State Key Laboratory of Photocatalysis on Energy and Environment, Department of Chemistry, Fuzhou University, Fuzhou, 350108, People's Republic of China. Electronic address:

This work developed a double ion-exchange reaction-based photoelectrochemical (PEC) immunoassay with the split-type detection mode for sensitive detection of prostate-specific antigen (PSA, used as a model). The nanocomposite of cadmium sulfide and nickel sulfide ([email protected] nanocomposite), as the photoactive material, was rapidly synthesized by two-step hydrothermal treatment. In the presence of target PSA, the cupric oxide nanoparticle (CuO NP) labeled detection antibody was introduced into the detection system by sandwich immunoreaction and the copper (Cu) ions was released from CuO nanoparticles by acid to participate in double ion-exchange reaction. The double ion-exchange reaction on the photoelectric sensing interface between Cu and [email protected] nanocomposites formed the weak photoactive material CuS (x = 1, 2) to reduce the photocurrent. Under optimal conditions, the double ion-exchange reaction-based PEC immunoassay exhibited good photocurrent responses toward target PSA within the dynamic working range from 0.01 ng mL to 50 ng mL at a low limit of detection (LOD) of 2.9 pg mL. Besides, our work could achieve good reproducibility and high specificity under the split-type detection mode. Compared with human PSA ELISA kit, the accuracy obtained by our strategy was satisfactory. Importantly, this Cu-activated double ion-exchange reaction-based PEC immunoassay provides a promising platform for the detection of biomarkers.
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http://dx.doi.org/10.1016/j.aca.2021.338215DOI Listing
March 2021