Publications by authors named "Lei Zhao"

2,712 Publications

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[Corrigendum] Benzyl isothiocyanate suppresses development and metastasis of murine mammary carcinoma by regulating the Wnt/β‑catenin pathway.

Mol Med Rep 2022 Oct 10;26(4). Epub 2022 Aug 10.

Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu 730000, P.R. China.

Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that the '1 M/Invasion' and the '2.5 M/Migration' panels shown in Fig. 3B on p. 1814 appeared to contain overlapping sections of data, such that they were potentially derived from the same original source, where these panels was intended to show the results from differently performed experiments. The authors have re‑examined their original data, and realize that Fig. 3B was inadvertently assembled incorrectly; specifically, the '2.5 M/Migration' panel was selected from the wrong data group. The revised version of Fig. 4, now containing the correct data for the '2.5 M/Migration' experiment in Fig. 3B, is shown on the next page. Note that this error did not adversely affect either the results or the overall conclusions reported in this study. All the authors agree with the publication of this corrigendum, and are grateful to the Editor of for allowing them the opportunity to publish this. They also wish to apologize to the readership of the Journal for any inconvenience caused. [Molecular Medicine Reports 20: 1808‑1818, 2019; DOI: 10.3892/mmr.2019.10390].
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http://dx.doi.org/10.3892/mmr.2022.12823DOI Listing
October 2022

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

Overview of recent progress in exogenous hydrogen supply biogas upgrading and future perspective.

Sci Total Environ 2022 Aug 2:157824. Epub 2022 Aug 2.

State Key Laboratory of Urban Water Resources and Environment, School of Environment, Harbin Institute of Technology, Harbin 150090, China.

With the rapid development of renewable and sustainable energy, biogas upgrading for producing high-quality biomethane as an alternative to natural gas has attracted worldwide attention. This paper comprehensively reviews the current state of biogas upgrading technologies. The advances in physicochemical, photosynthetic autotrophic, and chemical autotrophic biogas upgrading technologies are briefly described with particular attention to the key challenges. New chemical autotrophic biogas upgrading strategies, such as direct and indirect exogenous hydrogen supply, for overcoming barriers to biogas upgrading and realizing highly efficient bioconversion of carbon dioxide are summarized. For each approach to exogenous hydrogen supply for biogas upgrading, the key findings and technical limitations are summarized and critically analyzed. Finally, future developments are also discussed to provide a reference for the development of biogas upgrading technology that can address the global energy crisis and climate change issues related to the application of biogas.
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http://dx.doi.org/10.1016/j.scitotenv.2022.157824DOI Listing
August 2022

Anti-inflammatory potential of stevia residue extract against uric acid-associated renal injury in mice.

J Food Biochem 2022 Aug 5:e14286. Epub 2022 Aug 5.

Beijing Engineering and Technology Research Center of Food Additives, School of Food and Chemical Technology, Beijing Technology and Business University, Beijing, China.

Abnormal uric acid level result in the development of hyperuricemia and hallmark of various diseases, including renal injury, gout, cardiovascular disorders, and non-alcoholic fatty liver. This study was designed to explore the anti-inflammatory potential of stevia residue extract (STR) against hyperuricemia-associated renal injury in mice. The results revealed that STR at dosages of 150 and 300 mg/kg bw and allopurinol markedly modulated serum uric acid, blood urea nitrogen, and creatinine in hyperuricemic mice. Serum and renal cytokine levels (IL-18, IL-6, IL-1Β, and TNF-α) were also restored by STR treatments. Furthermore, mRNA and immunohistochemistry (IHC) analysis revealed that STR ameliorates UA (uric acid)-associated renal inflammation, fibrosis, and EMT (epithelial-mesenchymal transition) via MMPS (matrix metalloproteinases), inhibiting NF-κB/NLRP3 activation by the AMPK/SIRT1 pathway and modulating the JAK2-STAT3 and Nrf2 signaling pathways. In summary, the present study provided experimental evidence that STR is an ideal candidate for the treatment of hyperuricemia-mediated renal inflammation. PRACTICAL APPLICATIONS: The higher uric acid results in hyperuricemia and gout. The available options for the treatment of hyperuricemia and gout are the use of allopurinol, and colchicine drugs, etc. These drugs possess several undesirable side effect. The polyphenolic compounds are abundantly present in plants, for example, stevia residue extract (STR) exert a positive effect on human health. From this study results, we can recommend that polyphenolic compounds enrich STR could be applied to develop treatment options for the treatment of hyperuricemia and gout.
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http://dx.doi.org/10.1111/jfbc.14286DOI Listing
August 2022

Matrix metalloproteinase-responsive collagen-oxidized hyaluronic acid injectable hydrogels for osteoarthritic therapy.

Biomater Adv 2022 Jun 18;137:212804. Epub 2022 Apr 18.

Department of Pharmaceutics and Bioengineering, School of Chemical Engineering, Sichuan University, Chengdu 610065, PR China. Electronic address:

Drug delivery system and intra-articular injection have been clinically applied to prolong drug residence time and reduce side effects in the treatment of osteoarthrosis. Herein, injectable hydrogels with sustained-dexamethasone sodium phosphate (DSP) release behavior in response to matrix metalloproteinase (MMP) were developed for osteoarthritic therapy. Hyaluronic acid undergoes specific oxidation in the present of sodium periodate to prepare oxidized hyaluronic acid (OHA). Then the DSP-loaded collagen-based hydrogels (Col-OHA) were developed by the Schiff's base crosslinking between OHA and Type I collagen besides the self-assembly of collagen induced by OHA. The results indicate that the collagen self-assembly into collagen fibrils makes great contribution for shortening gelation time of Col-OHA hydrogels. Col-OHA hydrogels possess interconnected porous microstructure, good injectability, excellent self-healing performance, strong mechanical property, low swelling ability, good blood compatibility and no cytotoxicity. Significantly, Col-OHA hydrogels show highly sensitive and significantly substantially sustained release of DSP in response to MMP. DSP-loaded Col-OHA hydrogel possesses significant inhibition for the production of inflammatory cytokines in the joint synovium, which can effectively relieve the symptoms of osteoarthritis continuously. Col-OHA hydrogel has no obvious effect on liver and kidney functions. Overall, the Col-OHA hydrogels with excellent biocompatibility are the promising drug-loading system for the intra-articular injection therapy of osteoarthrosis.
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http://dx.doi.org/10.1016/j.bioadv.2022.212804DOI Listing
June 2022

Identification of the prognostic signature based on genomic instability-related alternative splicing in colorectal cancer and its regulatory network.

Front Bioeng Biotechnol 2022 18;10:841034. Epub 2022 Jul 18.

Centre for Lipid Research, Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Department of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.

Colorectal cancer (CRC) is a heterogeneous disease with many somatic mutations defining its genomic instability. Alternative Splicing (AS) events, are essential for maintaining genomic instability. However, the role of genomic instability-related AS events in CRC has not been investigated. From The Cancer Genome Atlas (TCGA) program, we obtained the splicing profiles, the single nucleotide polymorphism, transcriptomics, and clinical information of CRC. Combining somatic mutation and AS events data, a genomic instability-related AS signature was constructed for CRC. Mutations analyses, clinical stratification analyses, and multivariate Cox regression analyses evaluated this signature in training set. Subsequently, we validated the sensitivity and specificity of this prognostic signature using a test set and the entire TCGA dataset. We constructed a nomogram for the prognosis prediction of CRC patients. Differentially infiltrating immune cells were screened by using CIBERSORT. Inmmunophenoscore (IPS) analysis was used to evaluate the response of immunotherapy. The AS events-related splicing factors (SF) were analyzed by Pearson's correlation. The effects of SF regulating the prognostic AS events in proliferation and migration were validated in Caco2 cells. A prognostic signature consisting of seven AS events (PDHA1-88633-ES, KIAA1522-1632-AP, TATDN1-85088-ES, PRMT1-51042-ES, VEZT-23786-ES, AIG1-77972-AT, and PHF11-25891-AP) was constructed. Patients in the high-risk score group showed a higher somatic mutation. The genomic instability risk score was an independent variable associated with overall survival (OS), with a hazard ratio of a risk score of 1.537. The area under the curve of receiver operator characteristic curve of the genomic instability risk score in predicting the OS of CRC patients was 0.733. Furthermore, a nomogram was established and could be used clinically to stratify patients to predict prognosis. Patients defined as high-risk by this signature showed a lower proportion of eosinophils than the low-risk group. Patients with low risk were more sensitive to anti-CTLA4 immunotherapy. Additionally, HSPA1A and FAM50B were two SF regulating the OS-related AS. Downregulation of HSPA1A and FAM50B inhibited the proliferation and migration of Caco2 cells. We constructed an ideal prognostic signature reflecting the genomic instability and OS of CRC patients. HSPA1A and FAM50B were verified as two important SF regulating the OS-related AS.
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http://dx.doi.org/10.3389/fbioe.2022.841034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9340224PMC
July 2022

Enantioselective para-C(sp2)-H Functionalization of Alkyl Benzene Derivatives via Cooperative Catalysis of Gold/Chiral Brønsted Acid.

Angew Chem Int Ed Engl 2022 Aug 3. Epub 2022 Aug 3.

East China Normal University, School of Chemistry and Molecular Engineering, 500 Dongchuan Road, 200241, Shanghai, CHINA.

An asymmetric para-C(sp2)-H bond functionalization of alkyl benzene derivatives was successfully developed via cooperative catalysis of gold and chiral phosphoric acid (CPA), leading to synthetically useful chiral 1,1-diaryl motifs. Chiral phosphoric acid, ligand, and molecular sieves were found crucial for enantioselectivity control of this transformation. The salient features of this protocol include mild conditions, high efficiency, commercially available starting materials, highly chemo- and site- as well as enantioselective aromatic C-H functionalization, broad substrate scope, and extensive applications of the chiral products. The mechanistic studies suggested that two CPAs might be involved in chiral induction.
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http://dx.doi.org/10.1002/anie.202208874DOI Listing
August 2022

One-pot and rapid detection of SARS-CoV-2 viral particles in environment using SERS aptasensor based on a locking amplifier.

Sens Actuators B Chem 2022 Jul 29:132445. Epub 2022 Jul 29.

Shandong Provincial Key Laboratory of Detection Technology for Tumor Markers, Collaborative Innovation Center of Tumor Marker Detection Technology, Equipment and Diagnosis-Therapy Integration in Universities of Shandong, College of Chemistry and Chemical Engineering, Linyi University, Linyi 276005, P. R. China.

With the frequent detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in dwellings and wastewater, the risk of transmission of environmental contaminants is of great concern. Fast, simple and sensitive sensors are essential for timely detecting infection and controlling transmission through environment fomites. Herein, we developed a Surface Enhanced Raman Scattering (SERS) aptasensor, which can realize ultrasensitive and rapid assay of SARS-CoV-2 viral particles. In this strategy, we designed a novel locking amplifier which is activated only in the presence of virus by aptamer recognition. The reaction process was carried out though one-pot method at 37°C, which can save time and resources. In addition, magnetic beads used in reaction system can simplify operation, as well as provide ideas for developing biosensing robots via magnetic field. This SERS aptasensor can detect SARS-CoV-2 virus with a LOD of 260 TU/µL within 40 min in the linear range of 625-10000 TU/µL. Therefore, this convenience, speediness, sensitivity, and selectivity of detection has great prospects in analyzing SARS-CoV-2 viral particles or other viruses in environment as well as monitoring of environmental virus sources.
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http://dx.doi.org/10.1016/j.snb.2022.132445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9335397PMC
July 2022

Robot-assisted laparoscopic resection of a large left-sided pheochromocytoma: A case report.

Asian J Surg 2022 Jul 30. Epub 2022 Jul 30.

The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou, 730000, China; The First Clinical Medical College of Lanzhou University, Lanzhou, 730000, China; Department of Urology, Gansu Provincial Hospital, Lanzhou, 730000, China. Electronic address:

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http://dx.doi.org/10.1016/j.asjsur.2022.07.018DOI Listing
July 2022

A novel sulfide-driven denitrification methane oxidation (SDMO) system: Operational performance and metabolic mechanisms.

Water Res 2022 Jul 27;222:118909. Epub 2022 Jul 27.

State Key Laboratory of Urban Water Resource and Environment, School of Environment, Harbin Institute of Technology, Harbin, Heilongjiang 150090, China. Electronic address:

Microbial denitrification is a crucial biological process for the treatment of nitrogen-polluted water. Traditional denitrification process consumes external organic carbon leading to an increase in treatment costs. We developed a novel sulfide-driven denitrification methane oxidation (SDMO) system that integrates autotrophic denitrification (AD) and denitrification anaerobic methane oxidation (DAMO) for cost-effective denitrification and biogas utilization in situ. Two SDMO systems were operated for 735 days, with nitrate and nitrite serving as electron acceptors, to explore the performance of sewage denitrification and characterize metabolic mechanisms. Results showed SDMO system could reach as high as 100% efficiency of nitrogen removal and biogas desulfurization without an external carbon source when HRT was 10 days and inflow nitrogen concentrations were 50-100 mgN·L. Besides, nitrate was a preferable electron acceptor for SDMO system. Biogas not only enhanced nitrogen removal but also intensified the DAMO, nitrogen removed through DAMO contribution doubled as original period from 2.9 mgN·(L·d) to 6.2 mgN·(L·d), and the ratio of nitrate removal through AD to DAMO was 1.2:1 with nitrate as electron acceptor. While nitrogen removed almost all through AD contribution and DAMO was weaken as before, the ratio of nitrate removal through AD to DAMO was 21.2:1 with nitrite as electron acceptor. Biogas introduced into SDMO system with nitrate inspired the growth of DAMO bacteria Candidatus Methylomirabilis from 0.3% to 19.6% and motivated its potentiality to remove nitrate without ANME archaea participation accompanying with gene mfnE upregulating ∼100 times. According to the reconstructed genome from binning analysis, the dramatically upregulated gene mfnE was derived from Candidatus Methylomirabilis, which may represent a novel metabolism pathway for DAMO bacteria to replace the role of archaea for nitrate reduction.
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http://dx.doi.org/10.1016/j.watres.2022.118909DOI Listing
July 2022

Semi-analytic Fresnel diffraction calculation with polynomial decomposition.

Opt Lett 2022 Aug;47(15):3776-3779

The numerical method based on the fast Fourier transform (FFT) is generally applied to calculate the Fresnel diffraction field, which would suffer from sampling constraints. To break this limit, in this Letter, the semi-analytic Fresnel diffraction calculation method is proposed based on polynomial decomposition. The diffraction field is computed by using properly analytic Fresnel diffraction basis functions (FDBFs) according to the application requirements. Analytic FDBF is calculated based on Legendre or Chebyshev polynomials by using the object-domain frequency division multiplexing method. The proposed method offers arbitrary sampling, high-flexibility, and high-accuracy diffraction calculation in the full Fresnel region. The computational efficiency and accuracy of the proposed method are compared with FFT-based methods. It has potential application in light field analysis, wavefront sensing, and image processing.
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http://dx.doi.org/10.1364/OL.462972DOI Listing
August 2022

Research on the Mechanism of HRP Relieving IPEC-J2 Cells Immunological Stress Based on Transcriptome Sequencing Analysis.

Front Nutr 2022 15;9:944390. Epub 2022 Jul 15.

College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, China.

Early weaning increased the economic benefits of piglets. However, early weaning damages the intestinal barrier of piglets and causes immunological stress. The mechanism by which polysaccharide (HRP) alleviates lipopolysaccharide (LPS)-induced intestinal porcine epithelial cells (IPEC-J2) inflammatory damage was investigated using proteomics in our previous studies. In this study we employed RNA-sequencing (RNA-seq) to determine the level and function of differentially expressed genes (DEGs) and further explore the mechanism of the HRP anti-inflammatory and immune process. The differential expression analysis indicated that 3622, 1216, and 2100 DEGs in the IPEC-J2 cells were identified in C vs. L, L vs. H6-L, and C vs. H6-L, respectively. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis foundsix identified pathways related to the immune system. Additionally, we used the Science, Technology, Engineering, and Math (STEM) program to categorize the 3,134 DEGs that were differentially expressed in H2-L, H4-L and H6-L into eight possible expression profiles, in which 612 were clustered into two profiles. The accuracy and consistency of RNA-seq data were validated by the results of qRT-PCR of the nuclear factor of kappa light polypeptide gene enhancer in B-cells 2 (NFKB2), MAP kinase interacting serine/threonine kinase 2 (MKNK2), mitogen-activated protein kinase kinase 1 (MAP2K1), mitogen-activated protein kinase kinase kinase 8 (MAP3K8), Ras-related protein R-Ras (RRAS), TNF receptor-associated factor 1 (TRAF1), NF-kappa-B inhibitor alpha (NFKBIA), interleukin 8 (IL8), tumor necrosis factor, alpha-induced protein 3 (TNFAIP3), and transforming growth factor beta-1 (TGFB1). Transcriptome sequencing also indicated that HRP reduced the expression levels of related DEGs and inhibited the activation of the mitogen-activated protein kinase (MAPK)/nuclear factor kappa-B (NF-κB) signaling pathway. Our findings indicate that the application of HRP in piglet diets during the early weaning period can improve intestinal epithelial function and integrity, and relieve intestinal damage, and improve piglet health.
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http://dx.doi.org/10.3389/fnut.2022.944390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9336541PMC
July 2022

Intestinal epithelial β Klotho is a critical protective factor in alcohol-induced intestinal barrier dysfunction and liver injury.

EBioMedicine 2022 Jul 28;82:104181. Epub 2022 Jul 28.

Centre for Lipid Research, Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China. Electronic address:

Background: Intestinal barrier dysfunction is crucial in alcohol-associated liver disease (ALD). The decreased beta-Klotho (KLB) expression caused by gene variation is associated with hyperpermeability in patients with irritable bowel syndrome. Here we investigated the roles of intestinal KLB in maintaining the intestinal epithelial barrier in ALD and the underlying mechanisms.

Methods: We constructed the intestine-specific overexpression KLB mice to investigate the role of KLB on alcohol-induced intestinal barrier dysfunction and liver injury in an ALD mouse model. To investigate the molecular mechanism in vitro, Caco2 cells were cultured and infected with the KLB overexpression lentivirus, or transfected with KLB/TRPV6 siRNA, or TRPV6/FXR1 overexpression plasmid, and treated with or without ethanol.

Findings: The upregulation of KLB in enterocytes effectively protected mice from alcohol-induced intestinal barrier hyperpermeability, thereby ameliorating hepatic steatosis and inflammation. KLB competitively suppressed FXR1 binding to the TRPV6 mRNA, increasing TRPV6 mRNA stability and protein abundance in intestinal epithelial cells. Furthermore, KLB formed a complex with TRPV6 and tight junction (TJ) proteins, protecting against alcohol-induced TJ proteins endocytosis and degradation as well as intestinal barrier impairment.

Interpretation: This work suggested that KLB attenuated alcohol-induced intestinal epithelial barrier dysfunction and liver injury through FXR1/TRPV6/TJ proteins pathway.

Funding: National Natural Science Foundation of China, Chongqing Natural Science Foundation, Talent Project of Chongqing and the Science and Technology Research Program of Chongqing Municipal Education Commission.
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http://dx.doi.org/10.1016/j.ebiom.2022.104181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9352463PMC
July 2022

Automatic text classification of actionable radiology reports of tinnitus patients using bidirectional encoder representations from transformer (BERT) and in-domain pre-training (IDPT).

BMC Med Inform Decis Mak 2022 07 30;22(1):200. Epub 2022 Jul 30.

Department of Radiology, Beijing Friendship Hospital, Capital Medical University, No. 95 YongAn Road, Beijing, 100050, People's Republic of China.

Background: Given the increasing number of people suffering from tinnitus, the accurate categorization of patients with actionable reports is attractive in assisting clinical decision making. However, this process requires experienced physicians and significant human labor. Natural language processing (NLP) has shown great potential in big data analytics of medical texts; yet, its application to domain-specific analysis of radiology reports is limited.

Objective: The aim of this study is to propose a novel approach in classifying actionable radiology reports of tinnitus patients using bidirectional encoder representations from transformer BERT-based models and evaluate the benefits of in domain pre-training (IDPT) along with a sequence adaptation strategy.

Methods: A total of 5864 temporal bone computed tomography(CT) reports are labeled by two experienced radiologists as follows: (1) normal findings without notable lesions; (2) notable lesions but uncorrelated to tinnitus; and (3) at least one lesion considered as potential cause of tinnitus. We then constructed a framework consisting of deep learning (DL) neural networks and self-supervised BERT models. A tinnitus domain-specific corpus is used to pre-train the BERT model to further improve its embedding weights. In addition, we conducted an experiment to evaluate multiple groups of max sequence length settings in BERT to reduce the excessive quantity of calculations. After a comprehensive comparison of all metrics, we determined the most promising approach through the performance comparison of F1-scores and AUC values.

Results: In the first experiment, the BERT finetune model achieved a more promising result (AUC-0.868, F1-0.760) compared with that of the Word2Vec-based models(AUC-0.767, F1-0.733) on validation data. In the second experiment, the BERT in-domain pre-training model (AUC-0.948, F1-0.841) performed significantly better than the BERT based model(AUC-0.868, F1-0.760). Additionally, in the variants of BERT fine-tuning models, Mengzi achieved the highest AUC of 0.878 (F1-0.764). Finally, we found that the BERT max-sequence-length of 128 tokens achieved an AUC of 0.866 (F1-0.736), which is almost equal to the BERT max-sequence-length of 512 tokens (AUC-0.868,F1-0.760).

Conclusion: In conclusion, we developed a reliable BERT-based framework for tinnitus diagnosis from Chinese radiology reports, along with a sequence adaptation strategy to reduce computational resources while maintaining accuracy. The findings could provide a reference for NLP development in Chinese radiology reports.
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http://dx.doi.org/10.1186/s12911-022-01946-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9338483PMC
July 2022

Enhancing adoptive T cell therapy for solid tumor with cell-surface anchored immune checkpoint inhibitor nanogels.

Nanomedicine 2022 Jul 27;45:102591. Epub 2022 Jul 27.

College of Pharmaceutical Sciences, Soochow University, 199 Ren Ai Road, Suzhou Industrial Park, Suzhou 215123, PR China. Electronic address:

The efficacy of Adoptive Cell Therapy (ACT) for solid tumor is still mediocre. This is mainly because tumor cells can hijack ACT T cells' immune checkpoint pathways to exert immunosuppression in the tumor microenvironment. Immune Checkpoint Inhibitors such as anti-PD-1 (aPD1) can counter the immunosuppression, but the synergizing effects of aPD1 to ACT was still not satisfactory. Here we demonstrate an approach to safely anchor aPD1-formed nanogels onto T cell surface via bio-orthogonal click chemistry before adoptive transfer. The spatial-temporal co-existence of aPD1 with ACT T cells and the responsive drug release significantly improved the treatment outcome of ACT in murine solid tumor model. The average tumor weight of the group treated by cell-surface anchored aPD1 was only 18 % of the group treated by equivalent dose of free aPD1 and T cells. The technology can be broadly applicable in ACTs employing natural or Chimeric Antigen Receptor (CAR) T cells.
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http://dx.doi.org/10.1016/j.nano.2022.102591DOI Listing
July 2022

Neurokinin 1 and 2 receptors are involved in PGE- and citric acid-induced cough and ventilatory responses.

Respir Physiol Neurobiol 2022 Jul 26;306:103952. Epub 2022 Jul 26.

Pathophysiology Program, Lovelace Biomedical Research Institute, Albuquerque, NM 87108, USA. Electronic address:

Exposure to aerosolized citric acid (CA, 150 mM) and prostaglandin E (PGE, 0.43 mM) for 10 min in guinea pigs reportedly produces the distinct cough patterns (Type I vs. II) and ventilatory responses (long-lasting hyperventilation vs. brief tachypnea) even though triggering the same cough numbers. Type I and II coughs are primarily mediated by activation of TRPV1 and EP3 receptors (a PGE receptor) of vagal C-fibers respectively. Substance P (SP) and neurokinin A (NKA) released by vagal pulmonary sensory fibers peripherally are capable of affecting CA-induced cough and ventilation via preferentially activating neurokinin 1 and 2 receptors (NKR and NKR) respectively. This study aimed to define the impacts of CA- and PGE-exposure on pulmonary SP and NKA levels and the roles of NKR and NKR in modulating CA- and PGE-evoked cough and ventilatory responses. In unanesthetized guinea pigs, we determined: (1) pulmonary SP and NKA contents induced by the CA- or PGE-exposure; (2) effects of CP-99994 and SR-48968 (a NKR and a NKR antagonist respectively) given by intraperitoneal injection (IP) or aerosol inhalation (IH) on the CA- and PGE-evoked cough and ventilatory responses; and (3) immunocytochemical expressions of NKR/NKR in vagal C-neurons labeled by TRPV1 or EP3 receptors. We found that CA- and PGE-exposure evoked Type I and II cough respectively associated with different degrees of increases in pulmonary SP and NKA. Applications of CP-99994 and SR-48968 via IP and IH efficiently suppressed the cough responses to CA with less impact on the cough response to PGE. These antagonists inhibited or blocked the ventilatory response to CA and caused hypoventilation in response to PGE. Moreover, NKR and NKR were always co-expressed in vagal C-neurons labeled by TRPV1 or EP3 receptors. These results suggest that SP and NKA endogenously released by CA- and PGE-exposure play important roles in generating the cough and ventilatory responses to CA and PGE, at least in part, via activation of NKR and NKR expressed in vagal C-neurons (pulmonary C-neurons).
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http://dx.doi.org/10.1016/j.resp.2022.103952DOI Listing
July 2022

Alternations in neural oscillation related to attention network reveal influence of indoor toluene on cognition at low concentration.

Indoor Air 2022 Jul;32(7):e13067

General Medicine Department, Tianjin Medical University General Hospital, Tianjin, China.

Despite accumulative literature reporting negative impacts of high-concentration toluene, cognitive effects of toluene at low concentration are still unclear. Twenty-two healthy college students were exposed in a closed environmental chamber to investigate the influence of indoor toluene on cognitive performance and brain activity. During each toluene exposure condition (0 ppb, 17.5 ppb, 35 ppb, and 70 ppb), attention network test and electroencephalogram (EEG) recording were synchronously performed after 4-hour toluene exposure. Characteristic neural oscillation patterns in three attention networks were compared between four groups. The statistical analyses indicated that short-term exposure to toluene had no significant impact on behavioral performance of attention network. However, there was a significant increase in the power of theta and alpha band of executive network and orienting network in the whole brain, especially in frontal region when exposed to toluene. Besides, no significant difference was observed in alerting network. The alternations in neural oscillation demonstrated that more effort was required to accomplish the same tasks when exposed to toluene. The present study revealed that short-term exposure to toluene affected brain activity of attention network even at low concentration, which provided a theoretical basis for the development of safer evaluation methods and standards in the future.
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http://dx.doi.org/10.1111/ina.13067DOI Listing
July 2022

Abnormal Dynamic Functional Connectivity of the Left Rostral Hippocampus in Predicting Antidepressant Efficacy in Major Depressive Disorder.

Psychiatry Investig 2022 Jul 21;19(7):562-569. Epub 2022 Jul 21.

Center for Cognition and Brain Disorders, The Affiliated Hospital and Institutes of Psychological Sciences, Hangzhou Normal University, Hangzhou, China.

Objective: Some pharmacological treatments are ineffective in parts of patients with major depressive disorder (MDD), hence this needs prediction of effective treatment responses. The study aims to examine the relationship between dynamic functional connectivity (dFC) of the hippocampal subregion and antidepressant improvement of MDD patients and to estimate the capability of dFC to predict antidepressant efficacy.

Methods: The data were from 70 MDD patients and 43 healthy controls (HC); the dFC of hippocampal subregions was estimated by sliding-window approach based on resting-state functional magnetic resonance imaging (R-fMRI). After 3 months treatment, 36 patients underwent second R-fMRI scan and were then divided into the response group and non-response group according to clinical responses.

Results: The result manifested that MDD patients exhibited lower mean dFC of the left rostral hippocampus (rHipp.l) compared with HC. After 3 months therapy, the response group showed lower dFC of rHipp.l compared with the non-response group. The dFC of rHipp.l was also negatively correlated with the reduction rate of Hamilton Depression Rating Scale.

Conclusion: These findings highlighted the importance of rHipp in MDD from the dFC perspective. Detection and estimation of these changes might demonstrate helpful for comprehending the pathophysiological mechanism and for assessment of treatment reaction of MDD.
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http://dx.doi.org/10.30773/pi.2021.0386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9334807PMC
July 2022

Achieving visible and near-infrared dual-emitting mechanoluminescence in Mn single-doped magnesium aluminate spinel.

Dalton Trans 2022 Jul 28. Epub 2022 Jul 28.

Pillar of Engineering Product Development, Singapore University of Technology and Design, 8 Somapah Road, Singapore 487372, Singapore.

Visible (VIS) and near-infrared (NIR) mechanoluminescence (ML) materials have been developed rapidly for use in energy conversion, biological applications and mechanical sensing. The realization of visible and NIR ML in single host materials meets the dual requirements of visualization and anti-interference for high-precision mechanical sensing. In this work, Mn single-doped magnesium aluminate spinel MgAlO with excellent ML performance was studied in detail. Bright, visible green and NIR ML were achieved under mechanical stimulation, and the ratio between visible and NIR ML intensity can be regulated by manipulating the doping concentration of Mn. The generation of ML without additional pre-irradiation proved that the self-powered ML phenomenon was independent of trap. The functional relationship between mechanical parameters and ML intensity indicated that the doped spinel can be used for visualization, anti-interference and non-contact mechanical sensing. In addition, the NIR ML of MgAlO:Mn, centered at 835 nm, is located in the first NIR window (NIR-I, 650-950 nm), which effectively penetrates living tissue such as skin, fat, and lean meat, respectively, showing that it has potential applications in optical imaging.
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http://dx.doi.org/10.1039/d2dt01770aDOI Listing
July 2022

The Role of Osteopontin in Tumor Progression Through Tumor-Associated Macrophages.

Front Oncol 2022 8;12:953283. Epub 2022 Jul 8.

Key Laboratory of Organ Regeneration & Transplantation of the Ministry of Education, The First Hospital of Jilin University, Changchun, China.

Osteopontin (OPN) is a multifunctional phosphorylated protein. It is widely involved in solid tumor progression, such as intensification of macrophage recruitment, inhibition of T-cell activity, aggravation of tumor interstitial fibrosis, promotion of tumor metastasis, chemotherapy resistance, and angiogenesis. Most of these pathologies are affected by tumor-associated macrophages (TAMs), an important component of the tumor microenvironment (TME). TAMs have been extensively characterized, including their subsets, phenotypes, activation status, and functions, and are considered a promising therapeutic target for cancer treatment. This review focuses on the interaction between OPN and TAMs in mediating tumor progression. We discuss the strategies for targeting OPN and TAMs to treat cancer and factors that may affect the therapeutic outcomes of blocking OPN or depleting TAMs. We also discuss the role of cancer cell- vs. TAM-derived OPN in tumorigenesis, the mechanisms of how OPN affects TAM recruitment and polarization, and why OPN could mediate anti-tumor and pro-tumor effects, as well as previously reported discrepancies.
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http://dx.doi.org/10.3389/fonc.2022.953283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9309262PMC
July 2022

Circ_0018168 inhibits the proliferation and osteogenic differentiation of fibroblasts in ankylosing spondylitis via regulating miR-330-3p/DKK1 axis.

Regen Ther 2022 Dec 18;21:175-184. Epub 2022 Jul 18.

Department of Spinal Surgery, Harrison International Peace Hospital, Hengshui City, Hebei Province, China.

Background: Circular RNAs (circRNAs) play a crucial regulatory role in human diseases. However, the roles of circRNAs in ankylosing spondylitis (AS) are barely known. In this study, the functions of circ_0018168 in AS were investigated.

Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot assay were used for circ_0018168, microRNA-330-3p (miR-330-3p), dickkopf-1 (DKK1), alkaline phosphatase (ALP), osteocalcin (OCN), Runt-related transcription factor 2 (Runx2) levels. Cell Counting Kit-8 (CCK-8) assay and 5'-ethynyl-2'-deoxyuridine (EdU) assay were conducted to analyze cell proliferation ability. Flow cytometry analysis was manipulated for cell cycle process. ALP activity was examined with a commercial kit. RNA immunoprecipitation (RIP) assay, RNA pull-down assay and dual-luciferase reporter assay were used to analyze the relationships of circ_0018168, miR-330-3p and DKK1.

Results: Circ_0018168 and DKK1 levels were lowly expressed in AS hip capsule specimens. Circ_0018168 overexpression repressed cell proliferation, cell cycle process as well as reduced ALP activity and ALP, OCN and Runx2 protein levels in AS fibroblasts. DKK1 silencing ameliorated the impact of circ_0018168 on AS progression. In addition, circ_0018168 served as the sponge for miR-330-3p, which could target DKK1. MiR-330-3p inhibition suppressed the proliferation, cell cycle and osteogenic differentiation in AS fibroblasts, but DKK1 silencing reversed the impacts. Besides, the effect of circ_0018168 on AS development was abolished by miR-330-3p upregulation.

Conclusion: Circ_0018168 overexpression restrained fibroblast proliferation and osteogenic differentiation in AS by elevating DKK1 through adsorbing miR-330-3p.
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http://dx.doi.org/10.1016/j.reth.2022.06.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9304432PMC
December 2022

The Relationship between Microstructure and Fracture Behavior of TiAl/TiAlNb SPDB Joint with High Temperature Titanium Alloy Interlayers.

Materials (Basel) 2022 Jul 12;15(14). Epub 2022 Jul 12.

Institute of Special Environments Physical Sciences, Harbin Institute of Technology, Shenzhen 518055, China.

In this paper, spark plasma diffusion bonding technology was employed to join TiAl and TiAlNb with high temperature titanium alloy interlayer at 950 °C/10kN/60 min, then following furnace cooling at cooling rate up to 100 °C/min. After welding, the joint was aging heat-treated at 800 °C for 24 h. The microstructure and the elements diffusion of the TiAl/TiAlNb joint was analyzed by field emission scanning electron microscopy (FESEM) with EDS. Moreover, the tensile properties of the joint were tested at room temperature, 650 °C, and 750 °C. The results show that the spark plasma diffusion bonding formed a high quality TiAl/TiAlNb joint without microcracks or microvoids, while also effectively protecting the base metal. Significant differences in the microstructure of the joint appeared from TiAl side to TiAlNb side: TiAl BM (Base Metal) → DP(Duplex) and NG (Near-Gamma) → α-phase matrix with needle-like α-phase → bulk α-phase → needle-like α-phase → metastable β-phase → TiAlNb BM. After heat treatment at 800 °C for 24 h, the microstructure of the TiAl side and the interlayer region did not change, but the density and size of the needle-like α-phase in region 3 increased slightly. The microstructure of TiAlNb near the weld changed obviously, and a large number of fine O phases are precipitated from the metastable β phase matrix after heat treatment. Except for the TiAlN near-interface region, the effect of heat treatment on the microstructure of the joint is not significant. The microhardness of the joint is in the shape of a mountain peak. The maximum microhardness at the interface is above 500 HV, and it is significantly reduced to 400 HV after heat treatment. The fracture of the joint occurred at the interface at room temperature, 650 °C, and 750 °C. with the tensile strength 450 MPa, 540 MPa, and 471 Mpa, respectively, and mainly showing brittle fracture.
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http://dx.doi.org/10.3390/ma15144849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9316006PMC
July 2022

Optimization of Process Parameters and Analysis of Microstructure and Properties of 18Ni300 by Selective Laser Melting.

Materials (Basel) 2022 Jul 7;15(14). Epub 2022 Jul 7.

Chengdu Aeronautic Polytechnic, Chengdu 610100, China.

In this research, we studied the influence of process parameters on the quality of selective laser melting of 18Ni300 maraging steel. The effects of laser power and scanning speed on the relative density and hardness of 18Ni300 were studied by single-factor experiment and the orthogonal experimental method. The relative optimal process parameters of 18Ni300 were obtained when the layer thickness was 0.03 mm, and the hatch space was 0.1 mm. The microstructures and mechanical properties of the samples formed under different process parameters were characterized. The results showed that the optimal hardness and relative density of the sample were 44.7 HRC and 99.98% when the laser power was 230 W and the scanning speed was 1100 mm/s, respectively; the microstructure of the material was uniform and dense, exhibiting few pores. Some columnar crystals appeared along the boundary of the molten pool due to vertical epitaxial growth. The orientation of fine grains at the boundary of the molten pool was random, and some coarse columnar crystals in the molten pool exhibited a certain orientational preference along the <001> orientation. In the case of optimal process parameters, the SLM-formed 18Ni300 was composed of 99.5% martensite and 0.5% retained austenite; the indentation hardness was distributed in the range of 3.2-5 GPa. The indentation modulus was between 142.8-223.4 GPa, exhibiting stronger fluctuations than the indentation hardness. The sample's mechanical properties showed obvious anisotropy, while the tensile fracture characteristics exhibited necking. The tensile fracture morphology was ductile, and large equiaxed dimples and holes could be observed in the fiber area, accompanied by tearing characteristics.
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http://dx.doi.org/10.3390/ma15144757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9325139PMC
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

Novel Isoindolinone-Based Analogs of the Natural Cyclic Peptide Fenestin A: Synthesis and Antitumor Activity.

ACS Med Chem Lett 2022 Jul 29;13(7):1118-1124. Epub 2022 Jun 29.

Key Laboratory for Photonic and Electronic Bandgap Materials (Ministry of Education), College of Chemistry & Chemical Engineering, Harbin Normal University, Harbin 150025, P. R. China.

Small- and medium-sized cyclopeptides have been found to have extensive bioactivities and have drawn much attention from medicinal chemists. In the work described in this paper, various cyclic peptide analogs of Fenestin A were synthesized by intramolecular photoinduced electron-transfer cyclization reactions to study the influence of slight structural changes on the bioactivity of small cyclopeptides. The incorporation of thiazole and rigid isoindolinone fragments was found to improve the bioactivity of the cyclopeptide. Detailed studies of the apoptosis mechanism, mitochondrial membrane potential, cell cycle, intracellular Ca concentration, and lactate dehydrogenase activity following treatment with a cyclopeptide showed that the cyclopeptide could induce apoptosis of tumor cells and lead to cycle arrest in the G2/M phase. The research also suggested that the photoinduced reaction could be applied to construct cyclic peptides stereoselectively, and the introduction of rigid fragments could enhance the biological activity of cyclopeptide drugs.
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http://dx.doi.org/10.1021/acsmedchemlett.2c00149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9290000PMC
July 2022

Dietary Ferulic Acid Ameliorates Metabolism Syndrome-Associated Hyperuricemia in Rats Regulating Uric Acid Synthesis, Glycolipid Metabolism, and Hepatic Injury.

Front Nutr 2022 30;9:946556. Epub 2022 Jun 30.

Beijing Key Laboratory of Functional Food From Plant Resources, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China.

Ferulic acid is a well-known phenolic acid compound and possesses multiple health-promoting and pharmacological effects. Metabolic syndrome (MetS) and hyperuricemia (HUA) have become health problems worldwide and are closely connected. The aim of this study was to explore the influence of ferulic acid on MetS-related HUA and its underlying mechanisms. Rats were administered high-fructose and high-fat diet (HFFD) with or without ferulic acid (0.05 and 0.1%) for 20 weeks. Intake of HFFD resulted in obesity, hyperglycemia, insulin resistance, and dyslipidemia, which were alleviated by ferulic acid consumption. Treatment of rats with ferulic acid diminished the levels of lipids and inflammatory cytokines and enhanced the activities of antioxidant enzymes in the liver caused by HFFD. Additionally, administration of ferulic acid blocked a HFFD-induced elevation in activities and mRNA expression of enzymes involving in uric acid (UA) synthesis. Molecular docking analysis denoted that ferulic acid bound to the active center of these enzymes, indicative of the potential interaction with each other. These two aspects might partially be responsible for the decrement in serum UA content after ferulic acid ingestion. In conclusion, ferulic acid supplementation ameliorated lipid and glucose metabolic abnormalities, hepatic damage, and UA formation in MetS rats. There was a dose correlation between lipid deposition and UA synthesis-related indicators. These findings implied that ferulic acid could be applied as a promising dietary remedy for the management of MetS-associated HUA.
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http://dx.doi.org/10.3389/fnut.2022.946556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9280472PMC
June 2022

A dynamic predictive nomogram of long-term survival in primary gastric lymphoma: a retrospective study.

BMC Gastroenterol 2022 Jul 16;22(1):347. Epub 2022 Jul 16.

Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China.

Background: Primary gastric lymphoma (PGL) is the most common extranodal non-Hodgkin lymphoma (NHL). Due to the rarity of the disease, it is important to create a predictive model that provides treatment and prognosis for patients with PGL and physicians.

Methods: A total of 8898 and 127 patients diagnosed with PGL were obtained from the SEER database and from our Cancer Center as training and validation cohorts, respectively. Univariate and multivariate Cox proportional hazards models were used to investigate independent risk factors for the construction of predictive survival nomograms, and a web nomogram was developed for the dynamic prediction of survival of patients with PGL. The concordance index (C-index), calibration plot, and receiver operating characteristics (ROC) curve were used to evaluate and validate the nomogram models.

Results: There were 8898 PGL patients in the SEER cohort, most of whom were married men over the age of 60, 16.1% of the primary tumors were localized in the antrum and pylori of the stomach, which was similar to the composition of 127 patients in the Chinese cohort, making both groups comparable. The Nomogram of overall survival (OS) was compiled based on eight variables, including age at diagnosis, sex, race, marital status, histology, stage, radiotherapy and chemotherapy. Cancer-specific survival (CSS) nomogram was developed with eight variables, including age at diagnosis, sex, marital status, primary tumor site, histology, stage, radiotherapy and chemotherapy. The C-index of OS prediction nomogram was 0.948 (95% CI: 0.901-0.995) in the validation cohort, the calibration plots showed an optimal match and a high area below the ROC curve (AUC) was observed in both training and validation sets. Also, we established the first web-based PGL survival rate calculator ( https://yangjinru.shinyapps.io/DynNomapp/ ).

Conclusion: The web dynamic nomogram provided an insightful and applicable tool for evaluating PGL prognosis in OS and CSS, and can effectively guide individual treatment and monitoring.
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http://dx.doi.org/10.1186/s12876-022-02419-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9288002PMC
July 2022

Endogenous repair theory enriches construction strategies for orthopaedic biomaterials: a narrative review.

Biomater Transl 2021 28;2(4):343-360. Epub 2021 Dec 28.

Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.

The development of tissue engineering has led to new strategies for mitigating clinical problems; however, the design of the tissue engineering materials remains a challenge. The limited sources and inadequate function, potential risk of microbial or pathogen contamination, and high cost of cell expansion impair the efficacy and limit the application of exogenous cells in tissue engineering. However, endogenous cells in native tissues have been reported to be capable of spontaneous repair of the damaged tissue. These cells exhibit remarkable plasticity, and thus can differentiate or be reprogrammed to alter their phenotype and function after stimulation. After a comprehensive review, we found that the plasticity of these cells plays a major role in establishing the cell source in the mechanism involved in tissue regeneration. Tissue engineering materials that focus on assisting and promoting the natural self-repair function of endogenous cells may break through the limitations of exogenous seed cells and further expand the applications of tissue engineering materials in tissue repair. This review discusses the effects of endogenous cells, especially stem cells, on injured tissue repairing, and highlights the potential utilisation of endogenous repair in orthopaedic biomaterial constructions for bone, cartilage, and intervertebral disc regeneration.
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http://dx.doi.org/10.12336/biomatertransl.2021.04.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9255795PMC
December 2021

Proper animal experimental designs for preclinical research of biomaterials for intervertebral disc regeneration.

Biomater Transl 2021 28;2(2):91-142. Epub 2021 Jun 28.

Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.

Low back pain is a vital musculoskeletal disease that impairs life quality, leads to disability and imposes heavy economic burden on the society, while it is greatly attributed to intervertebral disc degeneration (IDD). However, the existing treatments, such as medicines, chiropractic adjustments and surgery, cannot achieve ideal disc regeneration. Therefore, advanced bioactive therapies are implemented, including stem cells delivery, bioreagents administration, and implantation of biomaterials etc. Among these researches, few reported unsatisfying regenerative outcomes. However, these advanced therapies have barely achieved successful clinical translation. The main reason for the inconsistency between satisfying preclinical results and poor clinical translation may largely rely on the animal models that cannot actually simulate the human disc degeneration. The inappropriate animal model also leads to difficulties in comparing the efficacies among biomaterials in different reaches. Therefore, animal models that better simulate the clinical charateristics of human IDD should be acknowledged. In addition, in vivo regenerative outcomes should be carefully evaluated to obtain robust results. Nevertheless, many researches neglect certain critical characteristics, such as adhesive properties for biomaterials blocking annulus fibrosus defects and hyperalgesia that is closely related to the clinical manifestations, e.g., low back pain. Herein, in this review, we summarized the animal models established for IDD, and highlighted the proper models and parameters that may result in acknowledged IDD models. Then, we discussed the existing biomaterials for disc regeneration and the characteristics that should be considered for regenerating different parts of discs. Finally, well-established assays and parameters for in vivo disc regeneration are explored.
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http://dx.doi.org/10.12336/biomatertransl.2021.02.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9255780PMC
June 2021
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