Publications by authors named "Xiaofei Liu"

229 Publications

A preliminary analysis of LncRNA biomarkers for schizophrenia.

Epigenomics 2021 Sep 16. Epub 2021 Sep 16.

Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan 030032, China.

The aim of this study was to identify the long noncoding RNAs (lncRNAs) associated with schizophrenia (SZ) and the relationships among their expression, antipsychotic efficacy and SZ severity. The diagnostic and predictive value of nine lncRNAs, , , , , , , , and , was investigated in 48 patients with SZ before and after antipsychotic treatment. , , , , , and were individually and collectively associated with, and predictive of, SZ pathogenesis. Moreover, increased expression of plasma , and levels was reversed after 12 weeks of antipsychotic treatment, which was associated with SZ severity. Seven lncRNAs serve as novel biomarkers for SZ diagnosis and prognosis and three lncRNAs are potential therapeutic targets.
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http://dx.doi.org/10.2217/epi-2021-0223DOI Listing
September 2021

Harnessing biocompatible nanofibers and silver nanoparticles for wound healing: Sandwich wound dressing versus commercial silver sulfadiazine dressing.

Mater Sci Eng C Mater Biol Appl 2021 Sep 30;128:112342. Epub 2021 Jul 30.

Department of Cosmetic and Plastic Surgery, Affiliated Hospital of Qingdao University, Qingdao 266071, China. Electronic address:

Owing to the structural replication of native extracellular matrix, nonwoven mats of electrospun nanofibers have great potential for use in wound healing. Herein, we report the design and fabrication of a sandwich wound dressing to balance its antimicrobial activity and biocompatibility. This success mainly relies on the incorporation of silver nanoparticles (AgNPs) into electrospun nanofibers, together with the rational design of a sandwich structure for the dressing. The bottom layer was composed of hydrophilic nanofibers made from a blend of polycaprolactone (PCL) and gelatin (Gel). The top layer consisted of hydrophobic PCL nanofibers. AgNP-loaded PCL/Gel nanofibers were sandwiched between the two layers. When compared with a commercial silver sulfadiazine dressing, the designed wound dressing showed competitive antimicrobial properties, lower cell toxicity, and accelerated wound closure for mouse skin injury. By balancing the biocompatibility of electrospun nanofibers and the broad-spectrum antibacterial activity of AgNPs within a sandwich structure, the novel multifunctional wound dressing could be valuable for effective wound healing and related applications.
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http://dx.doi.org/10.1016/j.msec.2021.112342DOI Listing
September 2021

Rationale, design and population description of the CREDENCE study: cardiovascular risk equations for diabetes patients from New Zealand and Chinese electronic health records.

Eur J Epidemiol 2021 Aug 22. Epub 2021 Aug 22.

Section of Epidemiology and Biostatistics, School of Population Health, University of Auckland, 30 Park Avenue, Grafton, Auckland, 1023, New Zealand.

The cardiovascular risk equations for diabetes patients from New Zealand and Chinese electronic health records (CREDENCE) study is a unique prospectively designed investigation of cardiovascular risk in two large contemporary cohorts of people with type 2 diabetes from New Zealand (NZ) and China. The study was designed to derive equivalent cardiovascular risk prediction equations in a developed and a developing country, using the same epidemiological and statistical methodology. Two similar cohorts of people with type 2 diabetes were identified from large general population studies in China and New Zealand, which had been generated from longitudinal electronic health record systems. The CREDENCE study aims to determine whether cardiovascular risk prediction equations derived in patients with type 2 diabetes in a developed country are applicable in a developing country, and vice versa, by deriving and validating equivalent diabetes-specific cardiovascular risk prediction models from the two countries. Baseline data in CREDENCE was collected from October 2004 in New Zealand and from January 2010 in China. In the first stage of CREDENCE, a total of 93,207 patients (46,649 from NZ and 46,558 from China) were followed until December 31st 2018. Median follow-up was 7.0 years (New Zealand) and 5.7 years (China). There were 5926 (7.7% fatal) CVD events in the New Zealand cohort and 3650 (8.8% fatal) in the Chinese cohort. The research results have implications for policy makers, clinicians and the public and will facilitate personalised management of cardiovascular risk in people with type 2 diabetes worldwide.
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http://dx.doi.org/10.1007/s10654-021-00795-9DOI Listing
August 2021

Copper nanoclusters promote tomato (Solanum lycopersicum L.) yield and quality through improving photosynthesis and roots growth.

Environ Pollut 2021 Aug 5;289:117912. Epub 2021 Aug 5.

Stockbridge School of Agriculture, University of Massachusetts, Amherst, MA, 01003, USA.

The innovative and sustainable technologies are highly needed to decrease serious environmental problems from current agriculture. Herein, the green and biosafe copper-based nano-agriculture was described for tomato production. Prepared Cu nanoclusters (NCs) showed small size (3.0 ± 0.5 nm) and high bioavailability. At low concentration (1 mg kg) in soil, Cu NCs improved the activities of antioxidant enzymes (superoxide dismutase, catalase and peroxidase) in the tomato plants, which could help to slow down leaf aging, increase photosynthesis and carbohydrates content by 19.4 % and 14.9 %, respectively. Cu NCs promoted the roots' growth, especially increasing the root tip' number, which might contribute to the increase in absorption of macronutrients (K, Mg and P) and micronutrients (B, Mn, Cu and Zn). The Cu NCs (1 mg kg) promoted tomato growth and increased the tomato fruit yields by 12.2 % compared to the control. Moreover, the tomato fruit qualities had been improved meanwhile the accumulation of Cu in fruits was not observed. These findings indicate that the Cu NCs have potential to be safely applied for tomato production.
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http://dx.doi.org/10.1016/j.envpol.2021.117912DOI Listing
August 2021

RtNAC100 involved in the regulation of ROS, Na accumulation and induced salt-related PCD through MeJA signal pathways in recretohalophyte Reaumuria trigyna.

Plant Sci 2021 Sep 15;310:110976. Epub 2021 Jun 15.

State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University, Hohhot, 010070, PR China; Key Laboratory of Herbage and Endemic Crop Biotechnology, and College of Life Sciences, Inner Mongolia University, Hohhot, 010070, China. Electronic address:

NAM, ATAF1/2, and CUC2 (NAC) proteins regulate plant responses to salt stress. However, the molecular mechanisms by which NAC proteins regulate salt-induced programmed cell death (PCD) are unclear. We identified 56 NAC genes, 35 of which had complete open reading frames with complete NAM domain, in the R. trigyna transcriptome. Salt stress and methyl jasmonate (MeJA) mediated PCD-induced leaf senescence in R. trigyna seedlings. Salt stress accelerated endogenous JA biosynthesis, upregulating RtNAC100 expression. This promoted salt-induced leaf senescence in R. trigyna by regulating RtRbohE and RtSAG12/20 and enhancing ROS accumulation. Transgenic assays showed that RtNAC100 overexpression aggravated salt-induced PCD in transgenic lines by promoting ROS and Na accumulation, ROS-Ca hub activation, and PCD-related gene expression. Therefore, RtNAC100 induces PCD via the MeJA signaling pathway in R. trigyna under salt stress.
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http://dx.doi.org/10.1016/j.plantsci.2021.110976DOI Listing
September 2021

Transcription factor specificity protein 1-mediated Serine/threonine kinase 39 upregulation promotes the proliferation, migration, invasion and epithelial-mesenchymal transition of hepatocellular carcinoma cells by activating the transforming growth factor-β1 /Smad2/3 pathway.

Bioengineered 2021 12;12(1):3566-3577

Department of Gastroenterology and Hepatology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.

Bioinformatics analysis showed that Serine/threonine kinase 39 (STK39), which was testified to play an important role in human cancers, may be a hub gene in diagnosing hepatocellular carcinoma (HCC). This study aimed to explore whether STK39 could be regulated by specificity protein 1 (SP1) to affect HCC cells malignant processes. Firstly, STK39 expression in tissues of HCC patients and several cell lines was analyzed. After STK39 silencing, cell proliferation was evaluated by methyl thiazolyl tetrazolium and colony formation assay. Tunel staining was used to detect cell apoptosis. Then, the abilities of cell migration and invasion were determined with wound healing and transwell assays. The expression of epithelial-mesenchymal transition (EMT)-related proteins and transforming growth factor-β1 (TGF-β1)/Smad2/3 pathway proteins was tested by western blot analysis. Thereafter, cells were overexpressed with SP1 under the circumstance of STK39 knockdown, and then the above cellular processes were under observation. Results revealed that the increased expression of STK39, which was found in both HHC patients and HCC cell lines, exhibited poor HCC prognosis. STK39 silencing inhibited Hep3b cell proliferation, migration, invasion, EMT and TGF-β1/Smad2/3 expression but promoted cell apoptosis. Additionally, SP1 could bind to the STK39 promoter and facilitate STK39 expression. Further studies revealed that the effects of STK39 silencing on Hep3b cells were blocked by SP1 overexpression. In conclusion, SP1-mediated STK39 up-regulation leads to the increased proliferation, migration, invasion and EMT of HCC cells via activating TGF-β1/Smad2/3 pathway. Therapies that target SP1 to knockdown STK39 expression may contribute to the inhibition of HCC progression.
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http://dx.doi.org/10.1080/21655979.2021.1947939DOI Listing
December 2021

Educational Approaches Help Bridge Perception Gaps of Invasive Alien Species (Mikania micrantha) between Managers and Non-managers.

Environ Manage 2021 Sep 17;68(3):340-352. Epub 2021 Jul 17.

Institute of International Rivers and Eco-Security, Yunnan University, South Section, East Outer Ring Road, Chenggong District, Kunming, Yunnan, 650500, China.

Invasive alien species (IAS) significantly impact biodiversity, human health, and economies, and considerable resources are often used to manage their spread. Few studies have focused on the human perception of IAS management, and little is known about approaches to improve stakeholder perception. This study examined perception gaps between managers and non-managers of a notorious weed Mikania micrantha and the preference for educational approaches to bridge those gaps. Household questionnaires and key informant interviews were conducted in the China-Myanmar Border Region (China), and ordinal logistic regressions and Wilcoxon rank sum tests were used in statistical analyses. We found a high level of perception of M. micrantha among stakeholders, and a significant influence of socio-demographic factors including gender, educational level, ethnic group, and geographical location. Scores of the identification, damage, control measure, and manual treatment of M. micrantha were significantly higher for managers than those for non-managers, indicating that there were certain perception gaps between two stakeholder groups. Nine educational approaches were identified as being effective in improving stakeholder perception of IAS, of which training workshops were mostly preferred, followed by brochures (or leaflets) and other promotional materials. Additionally, we propose that well-designed and well-conducted educational approaches would benefit stakeholder perception of IAS, and that integration of IAS management into a comprehensive rural development scheme would improve its long-term performance in marginalized rural communities.
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http://dx.doi.org/10.1007/s00267-021-01505-7DOI Listing
September 2021

Neuroprotective effects of Tiaogeng decoction against HO-induced oxidative injury and apoptosis in PC12 cells via Nrf2 and JNK signaling pathways.

J Ethnopharmacol 2021 Oct 30;279:114379. Epub 2021 Jun 30.

Department of Gynecology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China. Electronic address:

Ethnopharmacological Relevance: Tiaogeng decoction (TGD), a mixture of 10 traditional Chinese herbs, has been used clinically for over 30 years in treating menopause-related symptoms such as cognitive changes, mood disorders, vasomotor symptoms, and sleep disorders. These central nervous system symptoms are closely associated with declined ovarian function, which dramatically increases the risk of neurodegenerative disease. Previous studies revealed that TGD may have anti-oxidative and anti-apoptotic properties, potentially preventing neurodegenerative conditions; however, the underlying pharmacological mechanism remains unclear.

Aim Of The Study: This study aimed to examine whether TGD could activate the Nrf2 and C-Jun N-terminal kinase (JNK) signaling pathways to effectively reduce oxidative injury and apoptosis in PC12 cells and elucidate the mechanism by which this medicine may prevent neurodegenerative disease.

Materials And Methods: PC12 cells were exposed to different concentrations of TGD (125, 250, 500 μg/mL) and HO (150 μM). 17β-estradiol (0.05 μg/mL) was used as the positive control. A cell counting kit-8 (CCK-8) and a lactate dehydrogenase (LDH) assay were used to detect cell viability and cytotoxicity, while Hoechst and flow cytometry were performed to evaluate apoptosis levels. Mitochondrial function was assessed by measuring mitochondrial membrane potential (MMP), and superoxide dismutase (SOD), and reactive oxygen species (ROS) levels were used to measure oxidative stress (OS). Western blot analysis was used to identify the levels of Nrf2, phospho-JNK (p-JNK), phospho-mitogen-activated protein kinase kinase 7 (p-MKK7), Kelch-like ECH-associated protein 1 (Keap1), heme oxygenase-1 (HO-1), Caspase3 (Casp3), Caspase9 (Casp9), Bax, and Bcl-2 proteins. Moreover, JNK agonist anisomycin and Nrf2 inhibitor ML385 were used to validate pathways.

Results: TGD pretreatment significantly alleviated HO-induced cytotoxicity, apoptosis, MMP, and OS levels. HO stimulated the activation of Nrf2 and JNK signaling pathways, but TGD increased the extent of Nrf2 antioxidant activation, decreased the activation of JNK, and eventually reversed the HO-induced protein expression of p-MKK7, Keap1, HO-1, Cleaved Caspase3 (CL-Casp3), Cleaved Caspase9 (CL-Casp9), Bax, and Bcl-2.

Conclusions: This study's findings suggest that TGD may attenuate oxidative injury and apoptosis via the Nrf2 and JNK signaling pathways, making it a potential therapeutic candidate for neurodegenerative diseases.
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http://dx.doi.org/10.1016/j.jep.2021.114379DOI Listing
October 2021

Nonmonotonous Distance Dependence of van der Waals Screening by a Dielectric Layer.

J Phys Chem Lett 2021 May 20;12(20):4993-4999. Epub 2021 May 20.

State Key Laboratory of Mechanics and Control of Mechanical Structures, Key Laboratory for Intelligent Nano Materials and Devices of Ministry of Education, Nanjing University of Aeronautics and Astronautics, Nanjing 210016, China.

Van der Waals (vdW) screening or Faraday-cage-like screening of vdW interaction by monolayer crystals has recently been observed in experiments and understood from first-principles theories. Here, we investigate the vdW screening by a bulky dielectric layer using the Lifshitz theory. The ratio of vdW screening is found to depend on not only the interobject distance but also the thicknesses of the separated layers. Surprisingly, the screening ratio exhibits a nonmonotonous distance dependence, first increasing, but beyond a critical distance reducing, toward zero. The short-range trend coincides with that predicted for graphene-like trilayers by the random phase approximation, while the long-range trend poses a contrast to the increasing screening with distance by graphene predicted by the many-body dispersion approach. The positive correlation between the screening ratio and the dielectric constant revealed for atomistic layers is reproduced for the bulky dielectric layers.
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http://dx.doi.org/10.1021/acs.jpclett.1c00870DOI Listing
May 2021

Drug-eluting beads bronchial arterial chemoembolization plus intercostals arterial infusion chemotherapy is effective and well-tolerated in treating non-small cell lung cancer patients with refractory malignant pleural effusion.

J Thorac Dis 2021 Apr;13(4):2339-2350

Department of Pulmonary and Critical Care Medicine, The Eighth Medical Center of Chinese PLA General Hospital, College of Pulmonary and Critical Care Medicine, Chinese PLA General Hospital, Beijing, China.

Background: The study aimed to explore the efficacy and safety of drug-eluting beads bronchial arterial chemoembolization (DEB-BACE) plus intercostals arterial infusion chemotherapy in non-small cell lung cancer (NSCLC) patients with refractory malignant pleural effusion (MPE).

Methods: 17 NSCLC patients with refractory MPE treated by DEB-BACE plus the intercostals arterial infusion chemotherapy (DEB-BACE group) were recruited. Their treatment response [complete remission (CR), partial remission (PR), overall efficacy, failure] for MPE was assessed at 1 month after therapy; adverse effects were recorded; MPE progression-free survival and overall survival (OS) were calculated. Moreover, 19 NSCLC patients with refractory MPE treated by conventional chemotherapy were reviewed as control (chemotherapy group), then their medical records were collected.

Results: With respect to MPE response, DEB-BACE group exhibited increased CR (82.4% 10.5%, P<0.001) and overall efficacy (100.0% 52.6%, P=0.001), similar PR (17.6% 42.1%, P=0.112) while less failure (0.0% 47.4%, P=0.001) compared to chemotherapy group. Furthermore, OS was prolonged in DEB-BACE group (median: 13.4; 95% CI: 11.0-15.8 months) than chemotherapy group (median: 7.0; 95% CI: 4.4-9.6 months) (P=0.002). Further analyses displayed that in DEB-BACE group, CR was associated with improved ECOG score and longer MPE progression-free survival, and adverse events mainly included fever, chest distress/pain, gastrointestinal side effects, myelosuppression, rash and hemoptysis, which were all mild and tolerable.

Conclusions: DEB-BACE plus intercostals arterial infusion chemotherapy could serve as a salvage treatment option for NSCLC patients with refractory MPE.
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http://dx.doi.org/10.21037/jtd-20-1603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107566PMC
April 2021

HisPhosSite: A comprehensive database of histidine phosphorylated proteins and sites.

J Proteomics 2021 07 10;243:104262. Epub 2021 May 10.

Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing 210016, China. Electronic address:

Histidine phosphorylation is critically important in a variety of cellular processes including signal transduction, cell cycle, proliferation, differentiation, and apoptosis. It is estimated to account for 6% of all phosphorylated amino acids. However, due to the acid lability of the PN bond, the study of pHis lags far behind that of pSer, pThr, and pTyr. Recently, the development and use of pHis-specific antibodies and methodologies have led to a resurgence in the study of histidine phosphorylation. Although a considerable number of pHis proteins and sites have been discovered, most of them have not been manually curated and integrated to any databases. There is a lack of a data repository for pHis, and such work is expected to help further systemic studies of pHis. Thus, we present a comprehensive resource database of histidine phosphorylation (HisPhosSite) by curating experimentally validated pHis proteins and sites and compiling putative pHis sites with ortholog search. HisPhosSite contains 776 verified pHis sites and 2702 verified pHis proteins in 38 eukaryotic and prokaryotic species and 15,378 putative pHis sites and 10,816 putative pHis proteins in 1366 species. HisPhosSite provides rich annotations of pHis sites and proteins and multiple search engines (including motif search and BLAST search) for users to locate pHis sites of interest. HisPhosSite is available at http://reprod.njmu.edu.cn/hisphossite. SIGNIFICANCE: Histidine phosphorylation is involved in a variety of cellular processes as well as cancers, and it has been proved to be more common than previously thought. The HisPhosSite database was developed to collect pHis data from published literatures with experimental evidences. Unification of the identified pHis proteins and sites will give researchers an informative resource for histidine phosphorylation. HisPhosSite has a user-friendly interface with multiple search engines for users to locate pHis sites of interest. In addition, the database provides rich structural and functional annotations. HisPhosSite will help future studies and elucidation of the functions of histidine phosphorylation.
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http://dx.doi.org/10.1016/j.jprot.2021.104262DOI Listing
July 2021

Construction and validation of nomograms for predicting the prognosis of grade 3 endometrial endometrioid adenocarcinoma cancers: a SEER-based study.

Bioengineered 2021 12;12(1):1752-1765

Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.

Most cases of endometrial adenocarcinoma (EAC) are diagnosed early and have a good prognosis; however, grade 3 (G3) EACs have poor outcomes. We retrospectively analyzed the data of 11,519 patients with G3 EACs registered between 2004 and 2015 in the Surveillance, Epidemiology, and End Results Program database and constructed a nomogram to guide clinicians in decision-making and accurate prediction of the prognosis. The caret package was used to divide samples into a training set and a validation set. Univariate and multivariate Cox regression analyses were performed, and a nomogram was constructed. A calibration curve was plotted, and a decision curve analysis was performed to verify the accuracy and clinical utility in both cohorts. The Cox regression analysis revealed that age, race, tumor size, number of lymph nodes resected, International Federation of Gynecology and Obstetrics stage, tumor/node stage, and adjuvant therapy were the prognostic factors for G3 EAC, and these were included in the nomogram. The area under the curve values of the training cohort for 1-, 3-, and 5-year were 0.832, 0.798, and 0.784, respectively for the overall survival (OS) group, and 0.858, 0.812, and 0.799, respectively for the cancer specific survival (CSS) group. A nomogram was constructed to predict the survival rate of patients with G3 EACs more accurately. The predictive nomogram will help clinicians manage patients with G3 EACs more effectively in terms of clinical prognosis.
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http://dx.doi.org/10.1080/21655979.2021.1922247DOI Listing
December 2021

Prevention of Ischemic Myocardial Contracture Through Hemodynamically Controlled DCD.

Cardiovasc Eng Technol 2021 Apr 29. Epub 2021 Apr 29.

Division of Thoracic Surgery, Department of Clinical Sciences, Lund University, Lund, Sweden.

Purpose: Ischemic myocardial contracture (IMC) or "stone heart" is a condition with rapid onset following circulatory death. It inhibits transplantability of hearts donated upon circulatory death (DCD). We investigate the effectiveness of hemodynamic normalization upon withdrawal of life-sustaining therapy (WLST) in a large-animal controlled DCD model, with the hypothesis that reduction in cardiac work delays the onset of IMC.

Methods: A large-animal study was conducted comprising of a control group ([Formula: see text]) receiving no therapy upon WLST, and a test group ([Formula: see text]) subjected to a protocol for fully automated computer-controlled hemodynamic drug administration. Onset of IMC within 1 h following circulatory death defined the primary end-point. Cardiac work estimates based on pressure-volume loop concepts were developed and used to provide insight into the effectiveness of the proposed computer-controlled therapy.

Results: No test group individual developed IMC within [Formula: see text], whereas all control group individuals did (4/6 within [Formula: see text]).

Conclusion: Automatic dosing of hemodynamic drugs in the controlled DCD context has the potential to prevent onset of IMC up to [Formula: see text], enabling ethical and medically safe organ procurement. This has the potential to increase the use of DCD heart transplantation, which has been widely recognized as a means of meeting the growing demand for donor hearts.
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http://dx.doi.org/10.1007/s13239-021-00537-8DOI Listing
April 2021

Mn Fe O Hollow Nanostructures for High-Performance Asymmetric Supercapacitor Applications.

Chemistry 2021 Jun 28;27(36):9398-9405. Epub 2021 May 28.

School of Materials Science and Engineering, Ocean University of China, 266100, Qingdao, Shandong, P. R. China.

Design of hollow nanostructure and controllable phase of mixed metal oxides for improving performance in supercapacitor applications is highly desirable. Here we demonstrate the rational design and synthesis of Mn Fe O hollow nanostructures for supercapacitor applications. Owing to high porosity and the specific surface area that provides more active sites for electrochemical reactions, the electrochemical performance of Mn Fe O hollow nanostructure substantially enhanced comparing with pristine Mn O . Particularly, in 1.0 M KOH electrolyte, Mn Fe O with a typical diameter of 20 nm exhibits excellent specific capacitance of 2675, 2320, 1662, 987 F g at current densities of 1, 2, 5, 10 A g , respectively, which is significantly superior to those of other transition metal oxides. Besides, an asymmetric supercapacitor is assembled by using Mn Fe O and activated carbon as a positive and a negative electrode, respectively. Electrochemical results indicate a high energy density of 42 Wh kg at a power density of 0.75 kW kg , which makes this hollow nanostructure a highly promising electrode for achieving high-performance next-generation supercapacitors.
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http://dx.doi.org/10.1002/chem.202100768DOI Listing
June 2021

Behavior of the particulate matter (PM) emitted by trackless rubber-tyred vehicle (TRTV) at an idle speed under different movement conditions and ventilation optimization.

Sci Total Environ 2021 Aug 10;783:147008. Epub 2021 Apr 10.

College of Safety and Environmental Engineering, Shandong University of Science and Technology, Qingdao 266590, Shandong Province, China; State Key Laboratory of Mining Disaster Prevention and Control Co-found by Shandong Province and the Ministry of Science and Technology, Shandong University of Science and Technology, Qingdao 266590, China.

The particulate matter (PM) emitted by a trackless rubber-tyred vehicle (TRTV) in coal mines can seriously threaten the health and safety of the exposed workers underground. In this paper, in order to effectively reduce the PM concentration and improve the underground working environment, a combination of numerical simulations and field measurements was adopted to study the migration distribution of the PM emitted by a TRTV at an idle speed for 60 s under different movement conditions, and the dilution effects of the ventilation rate on the PM. The results showed that under different movement conditions, the PM mainly moved along the floor of the roadway, but upward diffusion trends were shown overall, which meant that the chambers are in high-risk areas. Field measurements were then performed under the two conditions to verify the effectiveness of the simulations. Furthermore, the dilution effects of the increased ventilation rate on the PM were analyzed. It was concluded that the optimal dilution ventilation rate under condition 1 was 4600m/min, and that under condition 2 was 2800m/min. Accordingly, the driver of the TRTV should try to move forward when entering the chamber.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147008DOI Listing
August 2021

Identification and Characterization of Long Non-coding RNAs in the Intestine of Olive Flounder () During Infection.

Front Immunol 2021 31;12:623764. Epub 2021 Mar 31.

School of Marine Science and Engineering, Qingdao Agricultural University, Qingdao, China.

Long non-coding RNAs (lncRNAs) play widespread roles in fundamental biological processes, including immune responses. The olive flounder (), an important economical flatfish widely cultured in Japan, Korea, and China, is threatened by infectious pathogens, including bacteria, viruses, and parasites. However, the role of lncRNAs in the immune responses of this species against pathogen infections is not well-understood. Therefore, in this study, we aimed to identify lncRNAs in the intestine of olive flounder and evaluate their differential expression profiles during infection, which is an important zoonotic and intestinal pathogen. A total of 4,445 putative lncRNAs were identified, including 3,975 novel lncRNAs and 470 annotated lncRNAs. These lncRNAs had shorter lengths and fewer exons compared with mRNAs. In total, 115 differentially expressed lncRNAs (DE-lncRNAs) were identified during infection. To validate the expression pattern of lncRNAs, six DE-lncRNAs were randomly selected for quantitative real-time PCR. The co-located and co-expressed mRNAs of DE-lncRNAs were predicted, which were used to conduct the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. The target genes of DE-lncRNAs enriched numerous immune-related processes and exhibited a strong correlation with immune-related signaling pathways. To better understand the extensive regulatory functions of lncRNAs, the lncRNA-miRNA-mRNA regulatory networks were constructed, and two potential competing endogenous RNA (ceRNA) networks, LNC_001979-novel_171-Potusc2 and LNC_001979-novel_171-Podad1, were preliminarily identified from the intestine of olive flounders for the first time. In conclusion, this study provides an invaluable annotation and expression profile of lncRNAs in the intestine of olive flounder infected with ; this forms a basis for further studies on the regulatory function of lncRNAs in the intestinal mucosal immune responses of olive flounder.
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http://dx.doi.org/10.3389/fimmu.2021.623764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044400PMC
September 2021

Identification and Development of Subtypes With Poor Prognosis in Pan-Gynecological Cancer Based on Gene Expression in the Glycolysis-Cholesterol Synthesis Axis.

Front Oncol 2021 24;11:636565. Epub 2021 Mar 24.

Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.

Metabolic reprogramming is an important biomarker of cancer. Metabolic adaptation driven by oncogenes allows tumor cells to survive and grow in a complex tumor microenvironment. The heterogeneity of tumor metabolism is related to survival time, somatic cell-driven gene mutations, and tumor subtypes. Using the heterogeneity of different metabolic pathways for the classification of gynecological pan-cancer is of great significance for clinical decision-making and prognosis prediction. RNA sequencing data for patients with ovarian, cervical, and endometrial cancer were downloaded from The Cancer Genome Atlas database. Genes related to glycolysis and cholesterol were extracted and clustered coherently by using . The mutations and copy number variations in different subtypes were compared, and the immune scores of the samples were evaluated. The R package was used to identify differentially expressed genes between subtypes, and the package (V0.4.2) was used to conduct Kyoto Encyclopedia of Genes and Genomes pathway and Gene Ontology functional enrichment analyses. A risk score model was constructed based on multivariate Cox analysis. Prognostic classification efficiency was analyzed by using , and internal and external cohorts were used to verify the robustness of the model. Based on the expression of 11 glycolysis-related genes and seven cholesterol-related genes, 1,204 samples were divided into four metabolic subtypes (quiescent, glycolysis, cholesterol, and mixed). Immune infiltration scores showed significant differences among the four subtypes. Survival analysis showed that the prognosis of the cholesterol subtype was better than that of the quiescent subtype. A nine-gene signature was constructed based on differentially expressed genes between the cholesterol and quiescent subtypes, and it was validated by using an independent cohort of the International Cancer Genome Consortium. Compared with existing models, our nine-gene signature had good prediction performance. The metabolic classification of gynecological pan-cancer based on metabolic reprogramming may provide an important basis for clinicians to choose treatment options, predict treatment resistance, and predict patients' clinical outcomes.
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http://dx.doi.org/10.3389/fonc.2021.636565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025671PMC
March 2021

Development of a colloidal gold immunochromatographic strip for the rapid detection of Channel catfish virus.

J AOAC Int 2021 Mar 31. Epub 2021 Mar 31.

Chinese Academy of Inspection and Quarantine, Beijing, 100176.

Background: channel catfish virus disease (CCVD) has resulted in great economic losses and has restricted the development of fisheries. There is therefore, a need for rapid and efficient diagnostic methods to control the spread of CCVD.

Objective: a colloidal gold immunochromatographic strip have been developed for the detection of CCVD.

Methods: in the study, a colloidal gold immunochromatographic strip for channel catfish virus (CCV) detection was developed using the monoclonal antibody 8B6 conjugated with colloidal gold as the detector antibody. A rabbit anti-CCV antibody was used as the capture complex at the test line, and goat anti-mouse IgG antibody was used as the capture antibody at the control line. The strip was characterized in its specificity, sensitivity and stability. In addition, an infection experiment was performed to test the applicability of the test strip.

Result: the strip was able to detect concentrations of the virus (104TCID50/mL) and showed analytical specificity when tested against other viral pathogens. The strips were still usable after 30 days of storage at 60 °C. It was possible to detect CCV experimentally in infected fish within 10-15 min using the strip.

Conclusions: the strip can be used as a rapid and convenient tool for on-site diagnosis to control outbreaks and the spread of CCVD.

Highlights: the immunochromatographic strip was firstly developed and applied for the detection of CCVD.
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http://dx.doi.org/10.1093/jaoacint/qsaa152DOI Listing
March 2021

Activity and Resistance-Related Point Mutations in Target Protein PcORP1 of Fluoxapiprolin in .

J Agric Food Chem 2021 Apr 25;69(13):3827-3835. Epub 2021 Mar 25.

State Key Laboratory of Crop Stress Biology for Arid Areas, College of Plant Protection, Northwest A&F University, 3 Taicheng Road, Yangling 712100, Shaanxi, People's Republic of China.

Fluoxapiprolin is a new piperidinyl thiazole isoxazoline fungicide developed by Bayer Crop Science in 2012, but the sensitivity and resistance mechanism of fluoxapiprolin are unclear. In this study, the sensitivities of 130 isolates to fluoxapiprolin were determined, and a unimodal distribution was observed with a mean EC value of 0.00043 μg/mL. Nine stable fluoxapiprolin-resistant mutants were obtained by fungicide adaption. The fitness of mutants was similar to or lower than that of the corresponding parental isolate. Seven heterozygous point mutations in the target protein PcORP1 were found in these mutants. These point mutations were confirmed in PsORP1 of homologue positions using the CRISPR/Cas9 system. G770V and N835S+I877F do confer high fluoxapiprolin resistance (resistance factor, RF > 1000), and ΔN835, N767I, and N837T+S910C lead to low resistance (RF < 100). transformants containing L733W, S768F, S768Y, Δ818/F819, N837Y, N837F, P861H, L863W, and I877Y in PsORP1 were also associated with high fluoxapiprolin resistance (RF > 100). In conclusion, the resistance risk of to fluoxapiprolin is moderate, and multiple point mutations in PcORP1 could confer different resistance levels to fluoxapiprolin.
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http://dx.doi.org/10.1021/acs.jafc.0c05119DOI Listing
April 2021

The molecular mechanisms of silica nanomaterials enhancing the rice (Oryza sativa L.) resistance to planthoppers (Nilaparvata lugens Stal).

Sci Total Environ 2021 May 30;767:144967. Epub 2021 Jan 30.

Stockbridge School of Agriculture, University of Massachusetts, Amherst, MA 01003, USA.

Herein, fluorescent silica (F-SiO) ENMs (50 nm) were synthesized, which could be taken up and translocated from rice root to shoot, promoting the plant growth and resistance to planthopper compared with Si ion fertilizers under hydroponic conditions. Particularly, upon exposure F-SiO ENMs (5 mg‧L) suspension for 9 days, the fresh and dry weight (FW and DW) of shoot, the root length, surface area, and tip number were increased by 33.58%, 65.22%, 15.26%, 20.26% and 29.01%, respectively. Notably, in the presence of planthopper, the shoot FW and DW still increased by 61.88% and 114.75%, respectively. The increased lignin content (by 30.13%) and formation of silica cells in stem after F-SiO ENMs exposure (5 mg‧L) could be mechanical barriers against planthoppers. The transcriptome data revealed that F-SiO ENMs could upregulate the expression of genes involved in plant-pathogen interactions, plant hormone signal transduction, glucose metabolism and carbon fixation pathway, promoting the growth and resistance of rice seedlings. Our findings provide first evidence for the underlying molecular mechanisms of SiO ENMs enhancing the rice resistance to planthopper.
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http://dx.doi.org/10.1016/j.scitotenv.2021.144967DOI Listing
May 2021

FSTL1 aggravates cigarette smoke-induced airway inflammation and airway remodeling by regulating autophagy.

BMC Pulm Med 2021 Jan 28;21(1):45. Epub 2021 Jan 28.

Department of Respiratory, Shandong Provincial Qianfoshan Hospital, Shandong University, The First Affiliated Hospital of Shandong First Medical University, Shandong Institute of Respiratory Diseases, #16766, Jingshi Road, Jinan CityShandong Province, 250014, China.

Background: Cigarette smoke (CS) is a major risk factor for Chronic Obstructive Pulmonary Disease (COPD). Follistatin-like protein 1 (FSTL1), a critical factor during embryogenesis particularly in respiratory lung development, is a novel mediator related to inflammation and tissue remodeling. We tried to investigate the role of FSTL1 in CS-induced autophagy dysregulation, airway inflammation and remodeling.

Methods: Serum and lung specimens were obtained from COPD patients and controls. Adult female wild-type (WT) mice, FSTL1 mice and FSTL1 mice were exposed to room air or chronic CS. Additionally, 3-methyladenine (3-MA), an inhibitor of autophagy, was applied in CS-exposed WT mice. The lung tissues and serum from patients and murine models were tested for FSTL1 and autophagy-associated protein expression by ELISA, western blotting and immunohistochemical. Autophagosome were observed using electron microscope technology. LTB4, IL-8 and TNF-α in bronchoalveolar lavage fluid of mice were examined using ELISA. Airway remodeling and lung function were also assessed.

Results: Both FSTL1 and autophagy biomarkers increased in COPD patients and CS-exposed WT mice. Autophagy activation was upregulated in CS-exposed mice accompanied by airway remodeling and airway inflammation. FSTL1 mice showed a lower level of CS-induced autophagy compared with the control mice. FSTL1 mice can also resist CS-induced inflammatory response, airway remodeling and impaired lung function. CS-exposed WT mice with 3-MA pretreatment have a similar manifestation with CS-exposed FSTL1 mice.

Conclusions: FSTL1 promotes CS-induced COPD by modulating autophagy, therefore targeting FSTL1 and autophagy may shed light on treating cigarette smoke-induced COPD.
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http://dx.doi.org/10.1186/s12890-021-01409-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841997PMC
January 2021

Molecular characterization, expression analysis and immune effect of Galectin-8 from Japanese flounder (Paralichthys olivaceus).

Fish Shellfish Immunol 2021 Apr 24;111:59-68. Epub 2021 Jan 24.

School of Marine Science and Engineering, Qingdao Agricultural University, Qingdao, 266109, China. Electronic address:

Galectin-8 gene belongs to the agglutinin family, which can specifically recognize β-galactoside bonds and play essential roles in many biological processes. In this study, we researched the sequence characteristics and immune-related function of Galectin-8 gene in Japanese flounder Paralichthys olivaceus, named PoGalectin-8. The results showed that the open reading frame of PoGalectin-8 was 891 bp, which encoding a protein with 296 amino acid residues and containing typical HXNPR and WGXEE motifs in the N-terminal and C-terminal CRD domains. Sequence alignment showed that PoGalectin-8 was conserved in different aquatic animals and exhibited the highest similarity (95.27%) with Seriola dumerili. PoGalectin-8 expressed in all detected tissues and exhibited the highest expression level in spleen, followed by skin and kidney. After infected by Edwardsiella tarda, the expression of PoGalectin-8 was down-regulated in the spleen and skin tissues of P. olivaceus. Further to study its immune-related functions, the recombinant PoGalectin-8 (rPoGalectin-8) was expressed and purified. The rPoGalectin-8 can specifically bind to lipopolysaccharide and peptidoglycan, the main components of cell walls from Gram-negative and Gram-positive bacteria. Bacteria binding and the microbial agglutinating experiments showed that the rPoGalectin-8 could bind and agglutinate all examined Gram-positive and Gram-negative bacteria. This study implied that PoGalectin-8, as a pattern recognition receptor, may play important roles during immune responses against bacterial infection, which laid a foundation for further functional identification of Galectin-8 in aquatic animal immunity.
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http://dx.doi.org/10.1016/j.fsi.2021.01.012DOI Listing
April 2021

Development of a multi-channel magnetic bead micro-probe assay for high-throughput detection of zearalenone in edible and medicinal Coix seed.

Food Chem 2021 Jun 6;347:128977. Epub 2021 Jan 6.

Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China. Electronic address:

A multi-channel magnetic bead micro-probes assay (MBPA) based on indirect competitive principle was developed for high-throughput detection of zearalenone (ZEA) in edible and medicinal Coix seed. This strategy introduced magnetic beads as the carriers, the specific primary antibodies as the capture probes for targets and the secondary antibodies functionalized goat anti-mouse immunoglobulin G labeled fluorescein isothiocyanate as the fluorescence signal probes. Through the competitive reaction of ZEA in Coix seed samples and that covalently coupled on the surface of MBs with their specific antibodies, as well as fast magnetic separation and sensitive fluorescence detection, the developed MBPA strategy allowed low limit of detection (2.03 ng/mL) with broad dynamic range (2.03-440.67 ng/mL), as well as excellent accuracy with the average recovery rate of 96.39% and relative standard deviation (RSD) of 5.48% for ZEA. 36 samples could realize simultaneous analysis in one operation within less than 20 min only needing 50 μL of solution and 30 s of sampling, avoiding large consumption of time and organic solvents. Multiple centrifugation and cleanup steps were omitted because of magnetic separation, avoiding the loss of targets. Diverse capture and fluorescent probes can be randomly bound onto the surface of MBs, making the MBPA strategy a promising tool for on-site high-throughput monitoring of various trace hazard factors in food safety, and environmental monitoring.
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http://dx.doi.org/10.1016/j.foodchem.2020.128977DOI Listing
June 2021

Reply to E. Younger et al, V. Sharma et al, and M. Uchihara et al.

J Clin Oncol 2021 03 13;39(7):864-865. Epub 2021 Jan 13.

Viktor Grünwald, MD, Interdisciplinary Genitourinary Oncology at the West-German Cancer Center, Clinic for Internal Medicine (Tumor Research) and Clinic for Urology, University Hospital Essen, Germany; Xiaofei Liu, MSc, Institute for Biostatistics, Medical School Hanover, Hanover, Germany; Markus Schuler, MD, Helios Clinic, Berlin, Germany; and Sebastian Bauer, MD, Clinic for Internal Medicine (Tumor Research), University Hospital Essen, Germany.

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http://dx.doi.org/10.1200/JCO.20.03272DOI Listing
March 2021

PRSS55 plays an important role in the structural differentiation and energy metabolism of sperm and is required for male fertility in mice.

J Cell Mol Med 2021 02 8;25(4):2040-2051. Epub 2021 Jan 8.

State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, China.

Orderly and stage-specifically expressed proteins are essential for spermatogenesis, and proteases play a key role in protein activation and function. The present study aimed to investigate serine protease 55 (PRSS55), which was reported to play a role in sperm-uterotubal junction (UTJ) migration and sperm-zona pellucida (ZP) binding. We found that PRSS55 was specifically expressed in testicular spermatids and epididymal spermatozoa. By constructing knockout mice targeting all transcripts of Prss55, we demonstrated that deletion of Prss55 resulted in a serious decline of male fertility, with significantly increased sperm malformation and decreased sperm motility. In Prss55 mice, increased structural abnormality, including deficient "9 + 2" microtubules, damaged peripheral dense fibre, and defective mitochondrial cristae, were found in sperm. In addition, sperm showed decreased expression of electron transfer chain molecules and lower ATP contents. These could be the potential causes of the astheno/teratozoospermia phenotype of the Prss55 mice, and provided new evidence for the previously reported impaired sperm-UTJ migration. Moreover, preliminary studies allowed us to speculate that PRSS55 might function by activating type II muscle myosin in the testis, which is involved in many processes requiring motivation and cytoskeleton translocation. Thus, PRSS55 is essential for the structural differentiation and energy metabolism of sperm, and might be a potential pathogenic factor in astheno/teratozoospermia. Our results provide an additional explanation for the male sterility of Prss55 mice, and further reveal the role of PRSS55.
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http://dx.doi.org/10.1111/jcmm.16116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882947PMC
February 2021

Behavior of diesel particulate matter transport from subsidiary transportation vehicle in mine.

Environ Pollut 2021 Feb 10;270:116264. Epub 2020 Dec 10.

College of Safety and Environmental Engineering, Shandong University of Science and Technology, Qingdao, 266590, Shandong Province, China; State Key Laboratory of Mining Disaster Prevention and Control Co-found By Shandong Province and the Ministry of Science and Technology, Shandong University of Science and Technology, Qingdao, 266590, China; Huozhou Coal Electricity Group Co., LTD, Linfen, 031400, Shanxi Province, China.

The aim of this study was to investigate thoroughly the diffusion and distribution of diesel particulate matter (DPM) discharged from a mine subsidiary transportation vehicle to improve the air quality in tunnels by reducing exhaust pollution and to propose targeted prevention measures. More specifically, the diffusion of DPM from a WC40Y shield carrier during its travel was examined in depth with numerical simulations. The results show that, under the current ventilation conditions, the airflow in the tunnel was insufficient for diluting the DPM discharged from the shield carrier during starting, accelerated traveling, and turning; this can be effectively addressed by increasing the ventilation rate to 1.8 m/s. However, during high-velocity travel, the carrier was affected by the piston wind could not be diluted effectively by increasing ventilation rate. The velocity limit can lower the DPM concentration in the tunnel and alleviate DPM pollution from the shield carrier. To reduce DPM emissions, the travel velocity should be limited to 30 km/h. Summary: Determine the optimal airflow velocity in the tunnel that ensures that the discharged DPM is effectively diluted during the travel of the shield carrier.
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http://dx.doi.org/10.1016/j.envpol.2020.116264DOI Listing
February 2021

MicroRNA‑223‑induced inhibition of the gene affects the proliferation and apoptosis of colorectal cancer cells via the Notch and Akt/mTOR pathways.

Mol Med Rep 2021 02 23;23(2). Epub 2020 Dec 23.

Department of Infectious Diseases, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.

The tumour suppressor gene F‑box and WD repeat domain‑containing 7 () plays an important role in human cancer by regulating cell division, proliferation and differentiation. However, the exact regulatory mechanisms of microRNA (miR)‑223 in colorectal cancer (CRC) cells are still unknown. The present study aimed to investigate the effect and mechanism of miR‑223 inhibiting on the proliferation and apoptosis of CRC cells. HCT116 cells were transfected with miR‑223 mimics or small interfering RNA (siRNA) targeting (si), and the effects of these treatments on cell proliferation and apoptosis were examined. The downstream Notch and Akt/mTOR pathways were also assessed. Following miR‑223 overexpression, the mRNA and protein expression levels of FBXW7 were downregulated. Transfection with miR‑223 mimics or si promoted the proliferation of HCT116 cells and inhibited apoptosis by promoting the Notch and Akt/mTOR signalling pathways. Conversely, miR‑223 mimics transfection with FBXW7 overexpression inhibited cell viability and restored apoptosis. Thus, the present study demonstrated that miR‑223 could bind to the gene and inhibit its expression, ultimately increasing the proliferation and preventing the apoptosis of CRC cells through the Notch and Akt/mTOR signalling pathways.
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http://dx.doi.org/10.3892/mmr.2020.11793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789109PMC
February 2021

Tiao Geng decoction inhibits tributyltin chloride-induced GT1-7 neuronal apoptosis through ASK1/MKK7/JNK signaling pathway.

J Ethnopharmacol 2021 Apr 15;269:113669. Epub 2020 Dec 15.

Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 20032, China. Electronic address:

Ethnopharmacological Relevance: Tiao Geng (TG) decoction is a Chinese herbal medicine extract that has been utilized for the treatment of menopausal symptoms for a history of over 30 years. In our previous study, we suggest that TG decoction possibly exerts an anti-apoptotic effect on hypothalamic neurons of ovariectomized rats via the ASK1/MKK7/JNK pathway. Tributyltin chloride (TBTC) causes oxidative damage and induces apoptosis of primary hypothalamic neurons in rats.

Aim Of The Study: The present work aimed to explore the inhibition of TG decoction on TBTC-induced GT1-7 cell apoptosis and its possible molecular mechanism.

Materials And Methods: The GT1-7 cell line was exposed to TG decoction at diverse doses (31.25, 62.5, 125 μg/mL) for 24 h and later with TBTC (1 mg/L) for 1 h, with 17β-E (100 nM) treatment being the positive control. Then, CCK8 assay was conducted to evaluate cell viability, while flow cytometric analysis was conducted to examine the apoptosis level. Related pathways and differentially expressed proteins were identified by tandem mass tag (TMT)-based quantitative phosphoproteomics. qRT-PCR was carried out to examine mRNA levels of Bax and B-cell lymphoma-2 (Bcl-2). Western blotting was performed to detect the levels of Bax, Bcl-2, c-Jun, c-Jun N-terminal kinase (JNK), Caspase-3 (Casp3), Mitogen-activated protein kinase kinase 7 (MKK7), and apoptosis signal-regulating kinase 1 (ASK1) . Finally, cells were pretreated with SP600125, an inhibitor of JNK, later the expression of JNK and Casp3 was measured.

Results: Application of TG decoction mitigated the GT1-7 cell apoptosis and injury caused by TBTC; besides, it inhibited the activation of the ASK1/MKK7/JNK pathway. Moreover, Bcl-2/Bax ratio became higher, and the MKK7, ASK1, Casp3 and c-Jun levels were inhibited. Besides, TG decoction combined with SP600125 (the JNK inhibitor) more significantly inhibited GT1-7 cell apoptosis caused by TBTC.

Conclusion: As discovered from the experiment in this study, TG decoction has a neuroprotective effect, which is achieved through inhibiting the ASK1/MKK7/JNK signal transduction pathway to reduce GT1-7 cell apoptosis.
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http://dx.doi.org/10.1016/j.jep.2020.113669DOI Listing
April 2021

Steering Transplant Immunosuppression by Measuring Virus-Specific T Cell Levels: The Randomized, Controlled IVIST Trial.

J Am Soc Nephrol 2021 02 15;32(2):502-516. Epub 2020 Dec 15.

Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hannover, Germany

Background: Pharmacokinetic monitoring is insufficient to estimate the intensity of immunosuppression after transplantation. Virus-specific T cells correlate with both virus-specific and general cellular immune defense. Additional steering of immunosuppressive therapy by virus-specific T cell levels might optimize dosing of immunosuppressants.

Methods: In a multicenter, randomized, controlled trial, we randomized 64 pediatric kidney recipients to a control group with trough-level monitoring of immunosuppressants or to an intervention group with additional steering of immunosuppressive therapy by levels of virus-specific T cells (quantified by cytokine flow cytometry). Both groups received immunosuppression with cyclosporin A and everolimus in the same target range of trough levels. Primary end point was eGFR 2 years after transplantation.

Results: In the primary analysis, we detected no difference in eGFR for the intervention and control groups 2 years after transplantation, although baseline eGFR 1 month after transplantation was lower in the intervention group versus the control group. Compared with controls, patients in the intervention group received significantly lower daily doses of everolimus and nonsignificantly lower doses of cyclosporin A, resulting in significantly lower trough levels of everolimus (3.5 versus 4.5 g/L, <0.001) and cyclosporin A (47.4 versus 64.1 g/L, <0.001). Only 20% of patients in the intervention group versus 47% in the control group received glucocorticoids 2 years after transplantation (=0.04). The groups had similar numbers of donor-specific antibodies and serious adverse events.

Conclusions: Steering immunosuppressive therapy by virus-specific T cell levels in addition to pharmacokinetic monitoring seems safe, results in a similar eGFR, and personalizes immunosuppressive therapy by lowering exposure to immunosuppressive drugs, likely resulting in lower drug costs.

Clinical Trial Registry Name And Registration Number: IVIST trial, https://www.clinicaltrialsregister.eu/ctr-search/search?query=2009-012436-32 and ISRCTN89806912.
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http://dx.doi.org/10.1681/ASN.2020050645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054884PMC
February 2021
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