Publications by authors named "Xiaoyu Li"

1,137 Publications

  • Page 1 of 1

Observation of a State X(2600) in the π^{+}π^{-}η' System in the Process J/ψ→γπ^{+}π^{-}η'.

Phys Rev Lett 2022 Jul;129(4):042001

Institute of High Energy Physics, Beijing 100049, People's Republic of China.

Based on (10087±44)×10^{6}  J/ψ events collected with the BESIII detector, the process J/ψ→γπ^{+}π^{-}η^{'} is studied using two largest decay channels of the η^{'} meson, η^{'}→γπ^{+}π^{-} and η^{'}→ηπ^{+}π^{-}, η→γγ. A new resonance, which we denote as the X(2600), is observed with a statistical significance larger than 20σ in the π^{+}π^{-}η^{'} invariant mass spectrum, and it has a connection to a structure around 1.5  GeV/c^{2} in the π^{+}π^{-} invariant mass spectrum. A simultaneous fit on the π^{+}π^{-}η^{'} and π^{+}π^{-} invariant mass spectra with the two η^{'} decay modes indicates that the mass and width of the X(2600) state are 2618.3±2.0_{-1.4}^{+16.3}  MeV/c^{2} and 195±5_{-17}^{+26}  MeV, where the first uncertainties are statistical, and the second systematic.
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http://dx.doi.org/10.1103/PhysRevLett.129.042001DOI Listing
July 2022

Development of a Novel Prognostic Model of Glioblastoma Based on m6A-Associated Immune Genes and Identification of a New Biomarker.

Front Oncol 2022 20;12:868415. Epub 2022 Jul 20.

Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Accumulating evidence shows that m6A regulates oncogene and tumor suppressor gene expression, thus playing a dual role in cancer. Likewise, there is a close relationship between the immune system and tumor development and progression. However, for glioblastoma, m6A-associated immunological markers remain to be identified.

Methods: We obtained gene expression, mutation, and clinical data on glioblastoma from The Cancer Genome Atlas and Chinese Glioma Genome Atlas databases. Next, we performed univariate COX-least absolute shrinkage and selection operator (LASSO)-multivariate COX regression analyses to establish a prognostic gene signature and develop a corresponding dynamic nomogram application. We then carried out a clustering analysis twice to categorize all samples according to their m6A-regulating and m6A-associated immune gene expression levels (high, medium, and low) and calculated their m6A score. Finally, we performed quantitative reverse transcription-polymerase chain reaction, cell counting kit-8, cell stemness detection, cell migration, and apoptosis detection assays to determine the biological role of CD81 in glioblastoma cells.

Results: Our glioblastoma risk score model had extremely high prediction efficacy, with the area under the receiver operating characteristic curve reaching 0.9. The web version of the dynamic nomogram application allows rapid and accurate calculation of patients' survival odds. Survival curves and Sankey diagrams indicated that the high-m6A score group corresponded to the groups expressing medium and low m6A-regulating gene levels and high m6A-associated prognostic immune gene levels. Moreover, these groups displayed lower survival rates and higher immune infiltration. Based on the gene set enrichment analysis, the pathophysiological mechanism may be related to the activation of the immunosuppressive function and related signaling pathways. Moreover, the risk score model allowed us to perform immunotherapy benefit assessment. Finally, silencing CD81 significantly suppressed proliferation, stemness, and migration and facilitated apoptosis in glioblastoma cells.

Conclusion: We developed an accurate and efficient prognostic model. Furthermore, the correlation analysis of different stratification methods with tumor microenvironment provided a basis for further pathophysiological mechanism exploration. Finally, CD81 may serve as a diagnostic and prognostic biomarker in glioblastoma.
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http://dx.doi.org/10.3389/fonc.2022.868415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9348864PMC
July 2022

PEGylated Recombinant Human Growth Hormone Jintrolong Exhibits Good Long-Term Safety in Cynomolgus Monkeys and Human Pediatric Growth Hormone Deficiency Patients.

Front Endocrinol (Lausanne) 2022 15;13:821588. Epub 2022 Jul 15.

Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Jintrolong is a long-acting PEGylated recombinant human growth hormone (PEG-rhGH) developed for weekly injection in patients with pediatric growth hormone deficiency (PGHD). Although PEG modification of therapeutic proteins is generally considered safe, concerns persist about the potential for adverse vacuolation in tissues with long-term exposure to PEG-included therapies, particularly in children. We assessed the safety of Jintrolong in cynomolgus monkeys with an examination of vacuolation in the brain choroid plexus (CP) and reported long-term clinical safety data obtained from children with PGHD. The toxicity of Jintrolong was assessed following the 52-week administration with doses at 0.3, 1, or 3 mg/kg/week. The levels of vacuolation of CP in animals were dose-dependent and at least partially reversible after a 104- or 157-week recovery period. Vacuolation in the CP epithelium did not lead to obvious subcellular structural or cell functional abnormalities. Compared with the clinical dose of 0.2 mg/kg/week Jintrolong in PGHD patients, exposure in monkeys under NOAEL 3 mg/kg/week exhibited safety margins greater than 120.5, the predicted minimum dose to induce vacuolation in monkeys is equivalent to 1.29 mg/kg/week in humans, which is 6.45-fold higher than the clinical dose. The safety data acquired in clinical trials for Jintrolong were also analyzed, which included phase III (360 patients), phase IV (3,000 patients) of 26-week treatment, and a follow-up study with treatment lasting for 3 years. There was no statistically significant difference in the incidence of adverse reactions between the Jintrolong group and the daily rhGH control group (no PEG), and no new adverse effects (AE) were observed in the Jintrolong group at the clinical therapeutic dose of 0.2 mg/kg/week.
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http://dx.doi.org/10.3389/fendo.2022.821588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9336684PMC
August 2022

Tegaserod Maleate Suppresses the Growth of Gastric Cancer In Vivo and In Vitro by Targeting MEK1/2.

Cancers (Basel) 2022 Jul 23;14(15). Epub 2022 Jul 23.

Pathophysiology Department, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China.

Gastric cancer (GC) ranks fifth in global incidence and fourth in mortality. The current treatments for GC include surgery, chemotherapy and radiotherapy. Although treatment strategies for GC have been improved over the last decade, the overall five-year survival rate remains less than 30%. Therefore, there is an urgent need to find novel therapeutic or preventive strategies to increase GC patient survival rates. In the current study, we found that tegaserod maleate, an FDA-approved drug, inhibited the proliferation of gastric cancer cells, bound to MEK1/2 and suppressed MEK1/2 kinase activity. Moreover, tegaserod maleate inhibited the progress of gastric cancer by depending on MEK1/2. Notably, we found that tegaserod maleate suppressed tumor growth in the patient-derived gastric xenograft (PDX) model. We further compared the effect between tegaserod maleate and trametinib, which is a clinical MEK1/2 inhibitor, and confirmed that tegaserod maleate has the same effect as trametinib in inhibiting the growth of GC. Our findings suggest that tegaserod maleate inhibited GC proliferation by targeting MEK1/2.
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http://dx.doi.org/10.3390/cancers14153592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9332868PMC
July 2022

Identifying Active Compounds and Mechanisms of Y. B. Chang against URTIs-Associated Inflammation by Network Pharmacology in Combination with Molecular Docking.

Evid Based Complement Alternat Med 2022 13;2022:2156157. Epub 2022 Jul 13.

School of Pharmacy, Hangzhou Medical College, Hangzhou, Zhejiang, China.

Purpose: The ripe fruits of , known as Quzhou Fructus Aurantii (QFA), have been commonly used for respiratory diseases. The purpose of this study was to investigate their active compounds and demonstrate their mechanism in the treatment of upper respiratory tract infections (URTIs) through network pharmacology and molecular docking.

Methods: The prominent compounds of QFA were acquired from TCMSP database. Their targets were retrieved from SwissTargetPrediction database, and target genes associated with URTIs were collected from DisGeNET and GeneCards databases. The target protein-protein interaction (PPI) network was constructed by using STRING database and Cytoscape. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were enriched. Visual compound-target-pathway network was established with Cytoscape. The effects of compounds were verified on the inhibitory activities against phosphoinositide 3-kinases (PI3Ks). Finally, the molecular docking was carried out to confirm the binding affinity of the bioactive compounds and target proteins.

Results: Five important active compounds, naringenin (NAR), tangeretin (TAN), luteolin (LUT), hesperetin (HES), and auraptene (AUR), were obtained. The enrichment analysis demonstrated that the pathways associated with inflammation mainly contained PI3K/Akt signalling pathway, TNF signalling pathway, and so on. The most important targets covering inflammation-related proteins might be PI3Ks. assays and molecular docking exhibited that TAN, LUT, and AUR acted as PI3K inhibitors.

Conclusion: The results revealed that QFA could treat URTIs through a multi-compound, multi-target, multi-pathway network, in which TAN, LUT, and AUR acted as PI3K inhibitors, probably contributing to a crucial role in treatment of URTIs.
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http://dx.doi.org/10.1155/2022/2156157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9300271PMC
July 2022

Affinity-Driven Site-Specific High Mannose Modification Determines the Structural Polymerization and Function of Tetrameric IgM in a Primitive Vertebrate.

J Immunol 2022 Jul 22. Epub 2022 Jul 22.

School of Life Sciences, South China Normal University, Institute of Modern Aquaculture Science and Engineering, Guangdong Provincial Key Laboratory for Healthy and Safe Aquaculture, Guangzhou, People's Republic of China;

Teleost tetramer IgM is the predominant Ig in the immune system and plays essential roles in host defense against microbial infection. Due to variable disulfide polymerization of the monomeric subunits, tetrameric IgM possesses considerable structural diversity. Previous work indicated that the teleost IgM H chain was fully occupied with complex-type -glycans. However, after challenge with trinitrophenyl (TNP) Ag, the complex -glycans in the Asn-509 site of IgM H chain transformed into high mannose. This study, therefore, was conducted to examine the functional roles of the affinity-related high-mannose modification in tilapia IgM. The TNP-specific IgM Ab affinity maturation was revealed in tilapia over the response. A positive correlation between TNP-specific IgM affinity and its disulfide polymerization level of isomeric structure was demonstrated. Mass spectrometric analysis indicated that the relationship between IgM affinity and disulfide polymerization was associated with the Asn-509 site-specific high-mannose modification. Furthermore, the increase of high mannose content promoted the combination of IgM and mannose receptor (MR) on the surface of phagocytes. Moreover, the increased interaction of IgM and MR amplified the phagocytic ability of phagocytes to To our knowledge, this study demonstrates that site-specific high-mannose modification associates with IgM Ab affinity and its structural disulfide polymerization and amplifies the phagocytosis of phagocytes by the combination of IgM and MR. The present study provides evidence for understanding the association of IgM structure and function during the evolution of the immune system.
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http://dx.doi.org/10.4049/jimmunol.2100921DOI Listing
July 2022

Observation of J/ψ Electromagnetic Dalitz Decays to X(1835), X(2120), and X(2370).

Phys Rev Lett 2022 Jul;129(2):022002

Turkish Accelerator Center Particle Factory Group, Istanbul Bilgi University, 34060 Eyup, Istanbul, Turkey.

Using a sample of about 10^{10}  J/ψ events collected at a center-of-mass energy sqrt[s]=3.097  GeV with the BESIII detector, the electromagnetic Dalitz decays J/ψ→e^{+}e^{-}π^{+}π^{-}η^{'}, with η^{'}→γπ^{+}π^{-} and η^{'}→π^{+}π^{-}η, have been studied. The decay J/ψ→e^{+}e^{-}X(1835) is observed with a significance of 15σ, and also an e^{+}e^{-} invariant-mass dependent transition form factor of J/ψ→e^{+}e^{-}X(1835) is presented for the first time. The intermediate states X(2120) and X(2370) are also observed in the π^{+}π^{-}η^{'} invariant-mass spectrum with significances of 5.3σ and 7.3σ. The corresponding product branching fractions for J/ψ→e^{+}e^{-}X, X→π^{+}π^{-}η^{'} [X=X(1835), X(2120), and X(2370)] are reported.
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http://dx.doi.org/10.1103/PhysRevLett.129.022002DOI Listing
July 2022

Exosomes from bone marrow mesenchymal stem cells decrease chemosensitivity of acute myeloid leukemia cells via delivering miR-10a.

Biochem Biophys Res Commun 2022 Jul 9;622:149-156. Epub 2022 Jul 9.

Department of Laboratory Medicine, School of Medical Technology and Engineering, Fujian Medical University, Fuzhou, 350004, PR China; Department of Clinical Laboratory, Fujian Medical University Union Hospital, Fuzhou, China. Electronic address:

Bone marrow mesenchymal stem cells (BMSCs) are an integral part of the acute myeloid leukemia (AML) bone marrow microenvironment and contribute to AML progression. In this study, we explored the communication between BMSCs and AML cells via exosomes. The AML cells co-cultured with BMSCs-Exos were found to have lower chemosensitivity exposed to cytarabine, suggesting that BMSCs-Exos could protect AML cells from cytarabine. Interestingly, miR-10a was elevated in BMSCs-Exos derived from AML (AML-BMSCs-Exos) compared with that from healthy donor. The expression levels of miR-10a in AML cells was significantly up-regulated after co-culture with BMSCs-Exos. Furthermore, the up-regulated miR-10a was an crucial factor contributing to the chemoresistance of leukemia cells. Down-regulation of miR-10a substantially increase chemosensitivity of AML cells treated with BMSCs-Exos. Chemosensitivity of AML cells was also decreased through down-regulating RPRD1A by miR-10a that ultimately lead to the stimulation of the Wnt/β-catenin signaling pathway. Collectively, our findings demonstrated that AML-BMSCs could deliver miR-10a to AML cells via exosomes, which could target RPRD1A and activate Wnt/β-catenin signaling pathway that subsequently decreased chemosensitivity of AML cells.
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http://dx.doi.org/10.1016/j.bbrc.2022.07.017DOI Listing
July 2022

Prognostic Role of M6A-Associated Immune Genes and Cluster-Related Tumor Microenvironment Analysis: A Multi-Omics Practice in Stomach Adenocarcinoma.

Front Cell Dev Biol 2022 24;10:935135. Epub 2022 Jun 24.

Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

N6-methylandrostenedione (m6A) methylation plays a very important role in the development of malignant tumors. The immune system is the key point in the progression of tumors, particularly in terms of tumor treatment and drug resistance. Tumor immunotherapy has now become a hot spot and a new approach for tumor treatment. However, as far as the stomach adenocarcinoma (STAD) is concerned, the in-depth research is still a gap in the m6A-associated immune markers. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases is extremely important for our research, where we obtained gene mutation, gene expression data and relevant clinical information of STAD patients. Firstly, the samples from GEO were used as external validation groups, while the TCGA samples were divided into a training group and an internal validation group randomly. Using the way of Single factor COX-LASSO- and multi-factor Cox to construct the prognostic model. Then, all samples were subjected to cluster analysis to generate high and low expression groups of immune gene. Meanwhile, we also collected the correlation between these types and tumor microenvironment. On this basis, a web version of the dynamic nomogram APP was developed. In addition, we performed microenvironmental correlation, copy number variation and mutation analyses for model genes. The prognostic model for STAD developed here demonstrated a very strong predictive ability. The results of cluster analysis manifested that the immune gene low expression group had lower survival rate and higher degree of immune infiltration. Therefore, the immune gene low expression group was associated with lower survival rates and a higher degree of immune infiltration. Gene set enrichment analysis suggested that the potential mechanism might be related to the activation of immunosuppressive functions and multiple signaling pathways. Correspondingly, the web version of the dynamic nomogram APP produced by the DynNom package has successfully achieved rapid and accurate calculation of patient survival rates. Finally, the multi-omics analysis of model genes further enriched the research content. Interference of RAB19 was confirmed to facilitate migration of STAD cells , while its overexpression inhibited these features. The prognostic model for STAD constructed in this study is accurate and efficient based on multi-omics analysis and experimental validation. Additionally, the results of the correlation analysis between the tumor microenvironment and m6Ascore are the basics of further exploration of the pathophysiological mechanism in STAD.
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http://dx.doi.org/10.3389/fcell.2022.935135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9291731PMC
June 2022

Quality Assessment of the Clinical Practice Guidelines of Ostomy Care Based on the AGREE II Instrument.

Front Public Health 2022 4;10:856325. Epub 2022 Jul 4.

School of Nursing, Beijing University of Chinese Medicine, Beijing, China.

Objectives: To assess the quality of clinical practice guidelines (CPGs) of ostomy care, and to analyze the status quo and challenges of guideline development.

Methods: CPGs of ostomy care were systematically searched in relevant guideline websites and electronic databases, including PubMed, ProQuest, Web of Science, CNKI, VIP, WANFANG, and SinoMed, from January 1, 2012, to November 24, 2021. Two appraisers used the Appraisal of Guidelines for Research and Evaluation, 2nd edition (AGREE II) instrument to assess the quality of the included CPGs independently and objectively. The consistency of assessment was calculated using intraclass correlation coefficients (ICC).

Results: A total of 5 CPGs relevant to ostomy care were assessed by AGREE II and the general quality of them was good. There were two CPGs of grade A and three CPGs of grade B. The domain scope and purpose (87.78%) had the highest scores, followed by the clarity of presentation (87.22%), the rigor of development (69.17%), stakeholder involvement (68.33%), and editorial independence (65.00%), and the lowest was applicability (55.42%). The overall assessment score was 5.40. All the ICCs for the AGREE II appraisal conducted by the two appraisers were >0.75.

Conclusions: The five CPGs of ostomy care have the potential to be adopted in clinical practice. However, they still have some room for improvement, especially in the applicability domain. The development of ostomy care CPGs should follow the evidence-based progress and methodology of guideline formulation specifications while considering the effects of the CPGs and the practical issues.
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http://dx.doi.org/10.3389/fpubh.2022.856325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9289137PMC
July 2022

regulates maize root growth and development by interacting with under the specific binding of .

PeerJ 2022 14;10:e13710. Epub 2022 Jul 14.

School of Life Sciences, Anhui Agricultural University, Hefei, Anhui, China.

Background: The auxin indole-3-acetic acid (IAA) is a type of endogenous plant hormone with a low concentration in plants, but it plays an important role in their growth and development. The gene family was found to be an early sensitive auxin gene with a complicated way of regulating growth and development in plants. The regulation of root growth and development by family genes has been reported in Arabidopsis, rice and maize.

Results: In this study, subcellular localization indicated that ZmIAA1-ZmIAA6 primarily played a role in the nucleus. A thermogram analysis showed that genes were highly expressed in the roots, which was also confirmed by the maize tissue expression patterns. In maize overexpressing , the length of the main root, the number of lateral roots, and the stalk height at the seedling stage were significantly increased compared with those of the wild type, while the EMS mutant was significantly reduced. The total number of roots and the dry weight of maize overexpressing at the mature stage were also significantly increased compared with those of the wild type, while those of the mutant was significantly reduced. Yeast one-hybrid experiments showed that could specifically bind to the promoter region. Bimolecular fluorescence complementation and yeast two-hybridization indicated an interaction between ZmIAA5 and ZmARF5.

Conclusions: Taken together, the results of this study indicate that regulates maize root growth and development by interacting with under the specific binding of .
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http://dx.doi.org/10.7717/peerj.13710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9288822PMC
July 2022

Near-Infrared-Responded High Sensitivity Nanoprobe for Steady and Visualized Detection of Albumin in Hepatic Organoids and Mouse Liver.

Adv Sci (Weinh) 2022 Jul 19:e2202505. Epub 2022 Jul 19.

Shandong Key Laboratory of Biophysics, Institute of Biophysics, College of Physics and Electronic Information, Dezhou University, Dezhou, 253023, China.

Exploring the advanced techniques for protein detection facilitates cell fate investigation. However, it remains challenging to quantify and visualize the protein with one single probe. Here, a luminescent approach to detect hepatic cell fate marker albumin in vitro and living cell labeling with upconversion nanoparticles (UCNPs), which are conjugated with antibody (Ab) and rose bengal hexanoic acid (RBHA) is reported. To guarantee the detection quality and accuracy, an "OFF-ON" strategy is adopted: in the presence of albumin, the luminescence of nanoparticles remains suppressed owing to energy transfer to the quencher. Upon albumin binding to the antibody, the luminescence is recovered under near-infrared light. In various bio-samples, the UCNPs-Ab-RBHA (UCAR) nanoprobe can sense albumin with a broad detection range (5-315 ng mL ). When applied to liver ductal organoid culture medium, the UCAR can monitor hepatocyte differentiation in real time by sensing the secreted albumin. Further, UCAR enables live imaging of cellular albumin in cells, organoids, and tissues. In a CCl -induced liver injury model, UCAR detects reduced albumin in liver tissue and serum. Thus, a biocompatible nanoprobe for both quantification and imaging of protein in complex biological environment with superior stability and high sensitivity is provided.
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http://dx.doi.org/10.1002/advs.202202505DOI Listing
July 2022

Construction of hierarchical polypyrrole coated copper-catecholate grown on poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) fibers for high-performance supercapacitors.

J Colloid Interface Sci 2022 Jul 11;627:142-150. Epub 2022 Jul 11.

Key Laboratory of Advanced Civil Engineering Materials, Ministry of Education, Shanghai Key Laboratory of Development and Application for Metal-Functional Materials, School of Materials Science & Engineering, Tongji University, 4800 Caoan Road, Shanghai 201804, China. Electronic address:

Fiber-shaped supercapacitors (FSCs) are considered as the optimal candidate for wearable energy devices, due to their high safety, excellent electrochemical stability, workability and body adaptability. However, the specific capacitances of today's FSCs such as carbon nanotube fibers and graphene fibers, are still not high enough for practical applications due to the limitation of their energy storage mode. So, we design a ternary composite fiber-shaped electrode: First, a kind of metal organic framework (MOF), copper-catecholate (Cu-CAT) nanorods, are in-situ grown on a wet-spun poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate) (PEDOT:PSS) fiber at the ambient temperature. Second, polypyrrole (PPy) is electrodeposited on the surface of the Cu-CAT/PEDOT:PSS fiber to obtain [email protected]@PEDOT:PSS fiber ([email protected]@PF). The growing Cu-CAT with high porosity anchored on the fiber surface provides electrochemical activate sites and the encapsulation of PPy effectively provides a continuous charge transfer path and improve its cycling stability. Notably, the [email protected]@PF electrode exhibits a satisfactory areal capacitance of 669.93 mF cm at 2 mA cm, which remains 61.66% even at a high current density of 20 mA cm. Furthermore, the assembled symmetric FSC displays excellent electrochemical properties and outstanding mechanical flexibility, demonstrating its feasibility as a wearable supercapacitor.
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http://dx.doi.org/10.1016/j.jcis.2022.07.050DOI Listing
July 2022

The kidney-expressed transcription factor ZKSCAN3 is dispensable for autophagy transcriptional regulation and AKI progression in mouse.

Mutat Res 2022 Jul 9;825:111790. Epub 2022 Jul 9.

Institute of Nephrology, and Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-communicable Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China. Electronic address:

Acute kidney injury (AKI) is a common clinical disease that can cause serious harm to the kidneys, but it has no effective treatment till now. The modulation of autophagy pathway regulation is considered a potentially effective therapeutic approach in AKI prevention and treatment. ZKSCAN3 has been shown to be an important transcription factor that negatively regulates autophagy activity in cancer tissues. In order to determine whether autophagy could be activated by knocking out ZKSCAN3 to exert the renal protective effect of autophagy, we constructed AKI models with Zkscan3 knockout (KO) mice and detected renal pathological changes and renal function changes as well as autophagy-related indicators. We found that Zkscan3 KO had no significant effect on kidney development. Besides, no significant changes in autophagy activity were observed under normal physiological or AKI conditions. In non-tumor tissues, ZKSCAN3 did not mediate transcriptional regulation of autophagy-related genes. These findings suggest that because ZKSCAN3 may not function in the transcriptional regulation of autophagy-related genes in non-tumor tissues, it may not be used as a therapeutic target for AKI.
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http://dx.doi.org/10.1016/j.mrfmmm.2022.111790DOI Listing
July 2022

Cu-TCPP Nanosheets-Sensitized Electrode for Simultaneous Determination of Hydroquinone and Catechol.

Materials (Basel) 2022 Jun 30;15(13). Epub 2022 Jun 30.

Hubei Key Laboratory of Radiation Chemistry and Functional Materials, School of Nuclear Technology and Chemistry & Biology, Hubei University of Science and Technology, Xianning 437100, China.

It is quite important to develop sensitive, simple, and convenient methods for the simultaneous determination of Hydroquinone (HQ) and Catechol (CC) due to their wide existence, the difficulty of degradation, and the high toxicity. Herein, Cu-TCPP nanosheets were prepared in ,-dimethylformamide (DMF) through the solvent exfoliation method. The morphology and electrochemical performance of Cu-TCPP were characterized, revealing its stacked sheet structure with abundant pores, a fast electron transfer ability, and a large electrode active area. Using Cu-TCPP nanosheets as the sensitive material to modify the glassy carbon electrodes (Cu-TCPP/GCEs), it was found that they had an obvious enhancement effect on the electrochemical oxidation currents of HQ and CC. The signal enhancement mechanism was explored. The Cu-TCPP nanosheets not only enhanced the accumulation abilities of HQ and CC, but also improved their apparent catalytic rate, displaying high sensitivity for HQ and CC. The values of the detection limit were calculated to be 3.4 and 2.3 nM for HQ and CC. A satisfactory recovery was obtained when this method was used in measuring HQ and CC in the water samples.
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http://dx.doi.org/10.3390/ma15134625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9267553PMC
June 2022

HF Resistant Porous Aromatic Frameworks for Electronic Special Gases Separation.

Langmuir 2022 Jul 1;38(28):8667-8676. Epub 2022 Jul 1.

School of Chemical Engineering and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi710049, China.

Here we report two HF acid resistant porous aromatic frameworks as adsorbents for high value-added electronic special gases (e.g., SF, NF, CF, Xe, Kr) separation. The New-PAF-1 and N-SOH exhibit exceptional adsorption selectivity for Xe and F-gases from semiconductor exhaust gas along with high physicochemical stability and excellent reusability, which have been collaboratively confirmed by single-component gas adsorption experiments, time-dependent adsorption rate tests, dynamic breakthrough experiments and regeneration tests. The theoretical calculations based on DFT and Mulliken atomic charge analyses elucidated the adsorption mechanism of New-PAF-1 and N-SOH toward F-gases, Xe, Kr, and N at molecular level, including adsorption site, binding energy and electrostatic potentials distribution. The systematic investigation sufficiently manifests that PAFs can act as highly stable porous adsorbents in harsh operating conditions.
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http://dx.doi.org/10.1021/acs.langmuir.2c01098DOI Listing
July 2022

insight into the self-assembly evolution of ABA-type block copolymers in water during the gelation process using infrared spectroscopy and near-infrared spectroscopy.

Phys Chem Chem Phys 2022 Jul 21;24(28):17004-17013. Epub 2022 Jul 21.

State Key Laboratory of Organic-Inorganic Composites, Beijing University of Chemical Technology, Beijing 100029, P. R. China.

As a kind of thermo-responsive hydrogel, amphiphilic block copolymers are widely investigated. However, the molecular mechanism of their structural change during the gelation process is still limited. Here, a well-controlled triblock copolymer poly(,-dimethylacrylamide)--poly(diacetone acrylamide)--poly(,-dimethylacrylamide) (PDMAA--PDAAM--PDMAA) was synthesized. Its optical microrheology results suggest a gelation temperature range from 42 to 50 °C, showing a transition from viscosity to elasticity. The morphological transition from spheres to worms occurs. Temperature-dependent IR spectra through two-dimensional correlation spectroscopy (2D-COS) and the Gaussian fitting technique were analyzed to obtain the transition information of the molecular structure within the triblock copolymer. The N-way principal component analysis (NPCA) on the temperature-dependent NIR spectra was performed to understand the molecular interaction between water and the copolymer. The intramolecular hydrogen bonds within the hydrophobic PDAAM block tend to dissociate with temperature, resulting in improved hydration and a relative volume increase of the PDAAM block. The dissociation of intermolecular hydrogen bonds within the PDAAM block was the driving force for the morphological transition. Moreover, the hydrophilic PDMAA block dehydrates with temperature, and three stages can be found. The dehydration rate of the second stage with temperature from 42 to 50 °C was obviously higher than those in the lower (first stage) and higher (third stage) temperature ranges.
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http://dx.doi.org/10.1039/d2cp00822jDOI Listing
July 2022

The Key Network of mRNAs and miRNAs Regulated by HIF1A in Hypoxic Hepatocellular Carcinoma Cells.

Front Genet 2022 14;13:857507. Epub 2022 Jun 14.

Ningxia Key Laboratory of Prevention and Control of Common Infectious Diseases, The School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, China.

Hypoxia plays an essential role in the progression of hepatocellular carcinoma (HCC), whereas hypoxia inducible factor-1 (HIF-1) is the key transcription factor allowing HCC to survive hypoxia. The aim of this study was to define the essential mRNAs and miRNAs regulated by HIF1A and dissect their functions, interactions, and tumor-infiltrating immune cells in HCC. A human HCC cell line HepG2 was used as a cell model of HCC. The CRISPR/Cas9 system was used to knock out in HepG2 cells, and RNA sequencing was utilized to characterize differentially expressed mRNAs and miRNAs in the -knockout HepG2 cells; the identified candidates were then analyzed by GO annotation and KEGG pathway enrichment to study their function and establish a PPI network. Quantitative (q) PCR was used to verify if there were significant differences in the expression of mRNAs, and the association of the selected mRNAs expression with immune cell infiltration levels was further analyzed using The Cancer Genome Atlas (TCGA) pan-cancer data. Using RNA-sequencing, we discovered that there were 1535 mRNAs differentially expressed (adjusted < 0.05, |fold change|>1.5) in the -knockout HepG2 cells, among which there were 644 mRNAs upregulated and 891 mRNAs downregulated. GO annotation and KEGG pathway enrichment showed that these mRNAs were involved in glycolysis/gluconeogenesis, PI3K-Akt signaling pathways, and HIF-1 signaling pathways. In addition, we found that there were 309 miRNAs differentially expressed (adjusted < 0.05, |fold change|>1.5) in the HIF1A-knockout HepG2 cells, of which there were 213 miRNAs upregulated and 96 miRNAs downregulated. Our further analyses uncovered that these miRNA putative targets were involved in the hippo signaling pathway, axon guidance, and tight junction. Moreover, the construction and analysis of the PPI network showed that , , and were recognized as hub genes with the highest connectivity degrees. Importantly, in the -knockout HepG2 cells, our qRT-PCR data confirmed the selected mRNA changes revealed by RNA-sequencing, and with TCGA pan-cancer data, we revealed that the expressional levels of these three genes, , , and , were associated with immune cell infiltration levels. The identified potential key network of mRNAs and miRNAs regulated by in the HCC cells suggests a key role of in the tumorigenesis of HCC.
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http://dx.doi.org/10.3389/fgene.2022.857507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9237512PMC
June 2022

Targeted peptide-modified oxidized mesoporous carbon nanospheres for chemo-thermo combined therapy of ovarian cancer .

Drug Deliv 2022 Dec;29(1):1947-1952

Department of Pharmacy, Zhongshan Hospital, Fudan University, Shanghai, China.

Ovarian cancer remains one of serious hazards to human health due to many drawbacks of existing available treatment options. In this study, a multifunctional chemo-thermo combined therapy nanoplatform (OMCNPID) was successfully prepared, which is composed of IP peptide as a targeting moiety to interleukin-6 receptors (IL-6Rs), oxidized mesoporous carbon nanospheres (OMCN) as a near infrared (NIR)-triggered drug carrier and doxorubicin (DOX) as a chemotherapeutic drug and fluorescent agent. The synthesized multifunctional nanoplatform displayed high storage capacity for drugs and excellent photothermal properties. Besides, DOX was rapidly released from OMCNPID at the condition of low pH and NIR laser irradiation due to the dissociation of DOX from graphitic cores of OMCN. experimental results verified that OMCNPID could be markedly taken up by SKOV-3 monolayer cells and tumor spheroids, and revealed a remarkable synergistic chemo-photothermal effect against ovarian cancer. All the results demonstrated that OMCNPID is a pH/NIR dual-stimulus responsive nanoplatform and can achieve efficient chemo-thermo combined therapy.
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http://dx.doi.org/10.1080/10717544.2022.2089298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9246175PMC
December 2022

DNA G-quadruplex structure participates in regulation of lipid metabolism through acyl-CoA binding protein.

Nucleic Acids Res 2022 Jun 24. Epub 2022 Jun 24.

Guangzhou Key Laboratory of Insect Development Regulation and Application Research, Institute of Insect Science and Technology, School of Life Sciences, South China Normal University, Guangzhou 510631, China.

G-quadruplex structure (G4) is a type of DNA secondary structure that widely exists in the genomes of many organisms. G4s are believed to participate in multiple biological processes. Acyl-CoA binding protein (ACBP), a ubiquitously expressed and highly conserved protein in eukaryotic cells, plays important roles in lipid metabolism by transporting and protecting acyl-CoA esters. Here, we report the functional identification of a G4 in the promoter of the ACBP gene in silkworm and human cancer cells. We found that G4 exists as a conserved element in the promoters of ACBP genes in invertebrates and vertebrates. The BmACBP G4 bound with G4-binding protein LARK regulated BmACBP transcription, which was blocked by the G4 stabilizer pyridostatin (PDS) and G4 antisense oligonucleotides. PDS treatment with fifth instar silkworm larvae decreased the BmACBP expression and triacylglycerides (TAG) level, resulting in reductions in fat body mass, body size and weight and growth and metamorphic rates. PDS treatment and knocking out of the HsACBP G4 in human hepatic adenocarcinoma HepG2 cells inhibited the expression of HsACBP and decreased the TAG level and cell proliferation. Altogether, our findings suggest that G4 of the ACBP genes is involved in regulation of lipid metabolism processes in invertebrates and vertebrates.
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http://dx.doi.org/10.1093/nar/gkac527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9262599PMC
June 2022

Continuous Vaginal Bleeding Induced By EGFR-TKI in Premenopausal Female Patients With EGFR Mutant NSCLC.

Front Oncol 2022 7;12:805538. Epub 2022 Jun 7.

Department of Thoracic Oncology of Cancer Center, West China Hospital, Sichuan University, Chengdu, China.

EGFR-TKI is widely used for EGFR-mutant NSCLC patients. Bleeding is reported as a neglected adverse effect induced by EGFR-TKI. Female patients with lung adenocarcinoma have a high frequency of EGFR mutations. This study investigated the effect of EGFR-TKI on the menstrual cycle, especially on bleeding, in women of childbearing age. The underlying mechanism was further investigated in a patient with severe bleeding. We retrospectively investigated the effects on menstrual cycle in premenopausal female NSCLC patients who underwent EGFR-TKI treatment during 2013 to 2019. Menstrual changes including cycle disorders and prolonged bleeding were investigated questionnaire survey. EGFR signaling, ER, PR and tissue factor expression were analyzed in endometrium tissue obtained from a 43-year-old patient who suffered from continuous vaginal bleeding during treatment with erlotinib and osimertinib. Among 42 premenopausal female patients taking EGFR tyrosine kinase inhibitor, 69.05% patients experienced abnormal menstruation. In women with abnormal menstruation, 41.37% had profuse menstruation and 20.69% had irregular menstruation. In most cases, the abnormal vaginal bleeding stopped when suspending EGFR-TKI. The EGFR-TKI induced abnormal vaginal bleeding might be associated with low progesterone level, decreased EGFR activation and tissue factor (TF) expression in endometrial tissues. EGFR-TKI unusually induce abnormal vaginal bleeding in premenopausal female NSCLC patients, which may be attributed to progesterone/EGFR/TF signaling. Megestrol acetate may be an available and effective drug for the uncommon adverse effect.
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http://dx.doi.org/10.3389/fonc.2022.805538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9210573PMC
June 2022

Confined microemulsion sono-polymerization of poly(ethylene glycol) nanoparticles for targeted delivery.

Chem Commun (Camb) 2022 Jul 12;58(56):7777-7780. Epub 2022 Jul 12.

Key Laboratory of Colloid and Interface Chemistry of the Ministry of Education, School of Chemistry and Chemical Engineering, Jinan, Shandong 250100, China.

Confined sono-polymerization is developed to prepare poly(ethylene glycol) nanoparticles within water-in-oil microemulsion, followed by post-functionalization with a bispecific antibody (anti HER2 and anti PEG) for targeted delivery of photosensitizers (, indocyanine green). The nanoparticles could specifically target to breast cancer cells (, SKBR3) that overexpress HER2 receptors for the inhibition of cancer cell growth under 808 nm laser irradiation. This study highlights a facile and controllable method to fabricate therapeutic nanoparticles capable of targeted delivery.
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http://dx.doi.org/10.1039/d2cc01874hDOI Listing
July 2022

Clinical application of oral Chinese Patent Medicines in ophthalmology: a scoping review protocol.

BMJ Open 2022 06 20;12(6):e059571. Epub 2022 Jun 20.

Eye Hospital, China Academy of Chinese Medical Sciences, Beijing, China.

Introduction: The prevalence of eye diseases has been increasing worldwide. In China, in addition to conventional medicine, Traditional Chinese Medicine (TCM) plays an important role in maintaining people's vision health. Although less flexible and targeted than TCM decoction, Chinese Patent Medicines (CPMs) are stable and well used. In recent years, CPMs have been increasingly used in ophthalmology clinics by TCM practitioners and by Western doctors in general hospitals. However, comprehensive evidence for using CPMs in ophthalmology is lacking.

Aim: We will apply the methodology of scoping review to systematically search and sort out the available evidence on oral CPMs for the treatment of eye diseases, identify the distribution of evidence in this field and provide a basis for clinical practice and medical decisions.

Methods: The scoping review will be implemented in the following seven steps: (1) defining the research question; (2) searching ), ) and ) for oral CPMs for the treatment of eye diseases; (3) searching Embase, Web of Science, PubMed, Cochrane Library, Chongqing VIP Chinese Scientific Journals Database, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database and Wanfang Database for relevant literature published from inception to December 2021; (4) developing eligibility criteria; (5) screening the studies based on inclusion criteria; (6) extracting relevant data and lastly, (7) collating, summarising and reporting the results.

Ethics And Dissemination: Since the scoping review aims at collecting data from publicly available publications, this study does not require ethical approval. The results will be published in a peer-reviewed journal and presented at scientific conferences.
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http://dx.doi.org/10.1136/bmjopen-2021-059571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9214408PMC
June 2022

Shenkang injection protects against renal fibrosis by reducing perforin expression through the STING/TBK1/IRF3 signaling pathways in natural killer cells.

Phytomedicine 2022 Sep 25;104:154206. Epub 2022 May 25.

Department of Nephrology, and Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-communicable Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China. Electronic address:

Background: Immune activation, chronic inflammation, and renal interstitial fibrosis (RIF) are associated with chronic kidney disease (CKD). The herbal formula, Shenkang injection (SKI), has been reported to attenuate RIF. However, the mechanisms by which SKI alleviates renal fibrosis, especially the role of natural killer (NK) cells, are unknown and require exploration.

Purpose: This study aimed to determine the mechanisms by which SKI alleviates RIF.

Methods: Differential gene expression between CKD mice and control groups was explored using bioinformatics analysis. To reveal how SKI reduces RIF in CKD, a CKD mouse model was established using folic acid for in vivo studies, and human kidney-2 cells were used for in vitro experiments. The effects of various SKI doses were then determined. Immunohistochemical staining, Enzyme-linked immunosorbent assay, western blotting, and quantitative real-time PCR were used for pathological and molecular expression detection.

Results: We first investigated the potential immune dysfunction in CKD using bioinformatics analysis. Some differentially expressed genes were enriched in immune-related functions. The expressions of perforin and interferon (IFN)-γ, which are mainly released by NK cells, were significantly higher in patients with CKD (p< 0.05). In vivo experiments showed that SKI alleviated renal fibrosis in a folic acid-induced renal fibrosis model. Serum creatinine and blood urea nitrogen levels were reduced in the high-dose SKI-treated group. Additionally, the mRNA and protein expression levels of type IV collagen and alpha-spinal muscular atrophy were reduced. Biochemical detection showed that SKI could also downregulate the activity of NK cells (by decreasing the expressions of perforin and IFN-γ). Increased levels of stimulator of interferon genes (STING)/TANK-binding kinase 1 (TBK1)/IFN regulatory factor 3 (IRF3), phosphorylation of TBK1, and IRF3 in FA-induced RIF mice were alleviated by SKI treatment, which was consistent with the results of in vitro experiments.

Conclusion: These results demonstrated that SKI could decrease the activation of NK cells via the STING/TBK1/IRF3 signaling pathway, thereby alleviating RIF and protecting renal function in CKD. This may provide valuable evidence supporting the clinical use of SKI in the treatment of patients with CKD.
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http://dx.doi.org/10.1016/j.phymed.2022.154206DOI Listing
September 2022

NLRP3-Dependent Pyroptosis: A Candidate Therapeutic Target for Depression.

Front Cell Neurosci 2022 26;16:863426. Epub 2022 May 26.

Sports Medicine Department, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, China.

Depression, a major public health problem, imposes a significant economic burden on society. Recent studies have gradually unveiled the important role of neuroinflammation in the pathogenesis of depression. Pyroptosis, a programmed cell death mediated by Gasdermins (GSDMs), is also considered to be an inflammatory cell death with links to inflammation. Pyroptosis has emerged as an important pathological mechanism in several neurological diseases and has been found to be involved in several neuroinflammatory-related diseases. A variety of chemical agents and natural products have been found to be capable of exerting therapeutic effects by modulating pyroptosis. Studies have shown that depression is closely associated with pyroptosis and the induced neuroinflammation of relevant brain regions, such as the hippocampus, amygdala, prefrontal cortex neurons, etc., in which the nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome plays a crucial role. This article provides a timely review of recent findings on the activation and regulation of pyroptosis in relation to depression.
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http://dx.doi.org/10.3389/fncel.2022.863426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204297PMC
May 2022

Neuroprotective effects of CysLTR antagonist on -induced meningitis in rats.

Exp Ther Med 2022 Jul 13;24(1):443. Epub 2022 May 13.

Department of Pharmacy, Hangzhou Children's Hospital, Hangzhou, Zhejiang 310014, P.R. China.

Cysteinyl leukotrienes (CysLTs) modulate central nervous system inflammatory responses via their receptors, CysLTR and CysLTR. It has been demonstrated that CysLTR participates in the infection process of (SP)-induced meningitis. In the present study, the effects and possible underlying mechanisms of CysLTR antagonists (pranlukast and HAMI 3379) on SP meningitis were further determined. SP meningitis was induced by intracerebroventricular injection of serotype III SP in Sprague-Dawley rats which were administrated intraperitoneally with 0.1 mg/kg antagonists. The clinical disease status of rats was evaluated by body weight and behavioral changes with neurological scoring. Survival neuron density, activated microglial and astrocytes were assessed by Nissl staining and immunohistochemical staining. The expression levels of inflammatory cytokines and NLRP3 inflammasome were detected by reverse transcription-quantitative PCR and western blotting, respectively. Pranlukast and HAMI 3379 treatment markedly alleviated the clinical disease status, which was manifested by improving body weight loss and neurological deficit. Furthermore, pranlukast and HAMI 3379 treatment ameliorated neuronal injury and inhibited microgliosis and astrogliosis. In addition, significant downregulation of inflammatory cytokines and NLRP3 expression was observed in pranlukast and HAMI 3379-treated rats. These findings indicated the neuroprotective effects of CysLTR antagonists against experimental SP-induced meningitis, and the mechanism of anti-inflammatory effects may partly be by inhibiting NLRP3 inflammasome overactivation.
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http://dx.doi.org/10.3892/etm.2022.11370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9185808PMC
July 2022

Microbial and enzymatic battle with food contaminant zearalenone (ZEN).

Appl Microbiol Biotechnol 2022 Jun 15;106(12):4353-4365. Epub 2022 Jun 15.

School of Bioengineering, Dalian University of Technology, No. 2 Linggong Road, Dalian, 116024, China.

Zearalenone (ZEN) contamination of various foods and feeds is an important global problem. In some animals and humans, ZEN causes significant health issues in addition to massive economic losses, annually. Therefore, removal or degradation of the ZEN in foods and feeds is required to be done. The conventional physical and chemical methods have some serious issues including poor efficiency, decrease in nutritional value, palatability of feed, and use of costly equipment. Research examined microbes from diverse media for their ability to degrade zearalenone and other toxins, and the findings of several investigations revealed that enzymes produced from microbes play a significant role in the degradation of mycotoxins. In established bacterial hosts, genetically engineered technique was used to enhance heterologously produced degrading enzymes. Then, the bio-degradation of ZEN by the use of micro-organisms or their enzymes is much more advantageous and is close to nature and ecofriendly. Furthermore, an effort is made to put forward the work done by different scientists on the biodegradation of ZEN by the use of fungi, yeast, bacteria, and/or their enzymes to degrade the ZEN to non-toxic products. KEY POINTS: •Evolved microbial strains degraded ZEA more quickly •Different degrading properties were studied.
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http://dx.doi.org/10.1007/s00253-022-12009-7DOI Listing
June 2022

Schlafen 5 suppresses human immunodeficiency virus type 1 transcription by commandeering cellular epigenetic machinery.

Nucleic Acids Res 2022 Jun 10. Epub 2022 Jun 10.

Institute of Medicinal Biotechnology, Chinese Academy of Medical Science, Beijing, China.

Schlafen-5 (SLFN5) is an interferon-induced protein of the Schlafen family, which are involved in immune responses and oncogenesis. To date, little is known regarding its anti-HIV-1 function. Here, the authors report that overexpression of SLFN5 inhibits HIV-1 replication and reduces viral mRNA levels, whereas depletion of endogenous SLFN5 promotes HIV-1 replication. Moreover, they show that SLFN5 markedly decreases the transcriptional activity of HIV-1 long terminal repeat (LTR) via binding to two sequences in the U5-R region, which consequently represses the recruitment of RNA polymerase II to the transcription initiation site. Mutagenesis studies show the importance of nuclear localization and the N-terminal 1-570 amino acids fragment in the inhibition of HIV-1. Further mechanistic studies demonstrate that SLFN5 interacts with components of the PRC2 complex, G9a and Histone H3, thereby promoting H3K27me2 and H3K27me3 modification leading to silencing HIV-1 transcription. In concert with this, they find that SLFN5 blocks the activation of latent HIV-1. Altogether, their findings demonstrate that SLFN5 is a transcriptional repressor of HIV-1 through epigenetic modulation and a potential determinant of HIV-1 latency.
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http://dx.doi.org/10.1093/nar/gkac489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9226525PMC
June 2022

A High Throughput Cell-Based Screen Assay for LINE-1 ORF1p Expression Inhibitors Using the In-Cell Western Technique.

Front Pharmacol 2022 24;13:881938. Epub 2022 May 24.

Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Long interspersed nuclear element 1 (LINE-1) is a dominant autonomous retrotransposon in human genomes which plays a role in affecting the structure and function of somatic genomes, resulting in human disorders including genetic disease and cancer. LINE-1 encoded ORF1p protein which possesses RNA-binding and nucleic acid chaperone activity, and interacts with LINE-1 RNA to form a ribonucleoprotein particle (RNP). ORF1p can be detected in many kinds of tumors and its overexpression has been regarded as a hallmark of histologically aggressive cancers. In this study, we developed an In-Cell Western (ICW) assay in T47D cells to screen the compounds which can decrease the expression of ORF1p. Using this assay, we screened 1,947 compounds from the natural products library of Target Mol and Selleckchem, among which three compounds, Hydroxyprogesterone, 2,2':5',2″-Terthiophene and Ethynyl estradiol displayed potency in diminishing LINE-1 ORF1p expression level. Further mechanistic studies indicated the compounds act by affecting LINE-1 RNA transcription. Notably, we demonstrated that the compounds have an inhibitory effect on the proliferation of several lung and breast cancer cell lines. Taken together, we established a high throughput screening system for ORF1p expression inhibitors and the identified compounds provide some clues to the development of a novel anti-tumor therapeutic strategy by targeting ORF1p.
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http://dx.doi.org/10.3389/fphar.2022.881938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9171067PMC
May 2022

Advances and Prospects in Antibacterial-Osteogenic Multifunctional Dental Implant Surface.

Front Bioeng Biotechnol 2022 24;10:921338. Epub 2022 May 24.

Department of Dental Implantology, Hospital of Stomatology, Jilin University, Changchun, China.

In recent years, dental implantation has become the preferred protocol for restoring dentition defects. Being the direct contact between implant and bone interface, osseointegration is the basis for implant exerting physiological functions. Nevertheless, biological complications such as insufficient bone volume, poor osseointegration, and postoperative infection can lead to implant failure. Emerging antibacterial-osteogenic multifunctional implant surfaces were designed to make up for these shortcomings both during the stage of forming osseointegration and in the long term of supporting the superstructure. In this mini-review, we summarized the recent antibacterial-osteogenic modifications of the dental implant surface. The effects of these modifications on biological performance like soft tissue integration, bone osteogenesis, and immune response were discussed. In addition, the clinical findings and prospects of emerging antibacterial-osteogenic implant materials were also discussed.
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http://dx.doi.org/10.3389/fbioe.2022.921338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9171039PMC
May 2022
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