Publications by authors named "Wei Ding"

962 Publications

Adverse event burden in older patients with CLL receiving bendamustine plus rituximab or ibrutinib regimens: Alliance A041202.

Leukemia 2021 Jul 17. Epub 2021 Jul 17.

Division of Hematology, The Ohio State University, Columbus, OH, USA.

Ibrutinib has superior progression-free survival compared with bendamustine plus rituximab (BR) in older CLL patients, however, differences in treatment duration, six monthly BR cycles versus continuous ibrutinib, complicate adverse event (AE) comparisons. We introduce the AE burden score (AE) to compare AEs, calculated for each patient by summing over products of reporting period length and grade for each all-cause grade 1-4 AE and dividing by the length of time over which AEs are assessed. A total of 176 patients received BR and 361 ibrutinib alone or with six cycles of rituximab. At 38 months median follow-up, 64% remained on ibrutinib. Median AE was higher with BR versus ibrutinib in the first six cycles (7.2 versus 4.9, p < 0.0001). Within ibrutinib arms, median AE decreased significantly to 3.7 after six cycles (p < 0.0001). 10% and 14% of BR and ibrutinib patients discontinued treatment for AEs. In ibrutinib arms, cumulative incidence of grade 3 or higher atrial fibrillation, hypertension, and infection (AEs of clinical interest) at 12 months was 4.5%, 17.5%, and 12.8%, respectively, and increased more slowly thereafter to 7.7%, 25.4%, and 20.5% at 36 months. Analytical tools including the AE and cumulative incidence of AEs can help to better characterize AE burden over time. ClinicalTrials.gov identifier: NCT01886872.
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http://dx.doi.org/10.1038/s41375-021-01342-xDOI Listing
July 2021

NDV related exosomes enhance NDV replication through exporting NLRX1 mRNA.

Vet Microbiol 2021 Jun 29;260:109167. Epub 2021 Jun 29.

Key Laboratory of Zoonosis Research, Ministry of Education, Jilin University, Changchun, 130062, China. Electronic address:

Virulent Newcastle disease virus (NDV) is a violent infection in avian species. The understanding of its pathogenic mechanism is consistently evolving along with the development of molecular biological advancement. Exosomes derived from NDV infected cells (NDV Ex) were reported to promote virus replication through transportation of viral proteins and miRNAs. However, the function of mRNAs in NDV Ex remains unknown. In this study, a novel mechanism of NDV Ex to facilitate NDV infection was explored. Through transcriptome analysis, seven immune related genes were found to up-regulate in NDV Ex. Among them, NLRX1 mRNA was notably enriched in NDV Ex, and decreased inside the cells after virulent NDV infection. Further investigation suggested that NLRX1 mRNA decrease was in accordance with the NLRX1 protein expression reduction. This process can be reversed by the inhibition of exosome release. Therefore, NDV infection could utilize NDV Ex to export NLRX1 mRNA and reduce cellular NLRX1 protein. As NLRX1 is a crucial anti-viral protein of MAVS signal pathway, and NDV Ex transported NLRX1 cannot counteract its function in recipient cells, it can be concluded that NDV could benefit its replication through exporting NLRX1 mRNA to relieve the anti-viral pressure on its survival.
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http://dx.doi.org/10.1016/j.vetmic.2021.109167DOI Listing
June 2021

GDF11 Alleviates Pathological Myocardial Remodeling in Diabetic Cardiomyopathy Through SIRT1-Dependent Regulation of Oxidative Stress and Apoptosis.

Front Cell Dev Biol 2021 28;9:686848. Epub 2021 Jun 28.

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

Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor β superfamily that alleviates cardiac hypertrophy, myocardial infarction, and vascular injury by regulating oxidative stress, inflammation, and cell survival. However, the roles and underlying mechanisms of GDF11 in diabetic cardiomyopathy (DCM) remain largely unknown. In this study, we sought to determine whether GDF11 could prevent DCM. After establishing a mouse model of diabetes by administering a high-fat diet and streptozotocin, intramyocardial injection of an adeno-associated virus was used to achieve myocardium-specific GDF11 overexpression. GDF11 remarkably improved cardiac dysfunction and interstitial fibrosis by reducing the levels of reactive oxygen species and protecting against cardiomyocyte loss. Mechanistically, decreased sirtuin 1 (SIRT1) expression and activity were observed in diabetic mice, which was significantly increased after GDF11 overexpression. To further explore how SIRT1 mediates the role of GDF11, the selective inhibitor EX527 was used to block SIRT1 signaling pathway, which abolished the protective effects of GDF11 against DCM. studies confirmed that GDF11 protected against H9c2 cell injury in high glucose and palmitate by attenuating oxidative injury and apoptosis, and these effects were eliminated by SIRT1 depletion. Our results demonstrate for the first time that GDF11 protects against DCM by regulating SIRT1 signaling pathway.
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http://dx.doi.org/10.3389/fcell.2021.686848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273395PMC
June 2021

Sustainable natural bioresources in crop protection: antimicrobial hydroxycoumarins induce membrane depolarization-associated changes in the transcriptome of Ralstonia solanacearum.

Pest Manag Sci 2021 Jul 13. Epub 2021 Jul 13.

Laboratory of Natural Products Pesticides, College of Plant Protection, Southwest University, Chongqing, 400715, China.

Background: Ralstonia solanacearum is one of the most devastating pathogen affect crop production worldwide. Hydroxycoumarin (umbelliferone, esculetin, daphnetin) imply as sustainable natural bioresources on controlling of plant bacterial wilt. However, the antibacterial mechanism of hydroxycoumarins against plant pathogen still remains poorly understood.

Results: Here we characterized the effect of three hydroxycoumarins on the transcriptome of R. solanacearum. All three hydroxycoumarins were able to kill R. solanacearum, but their antibacterial activity impacted differently the bacterial transcriptome, indicating that their modes of action might be different. Treatment of R. solanacearum cultures with hydroxycoumarins resulted in a large number of the differentially expressed genes (DEGs), involved in basic cellular functions and metabolic process, such as downregulation of genes involved in fatty acid synthesis, lipopolysaccharides biosynthesis, RNA modification, ribosomal submits, oxidative phosphorylation and electrontransport, as well as upregulation of genes involved in transcriptional regulators, drug efflux, and oxidative stress responses. Future studies based on in vitro experiments are proposed to investigate lipopolysaccharides biosynthesis pathway leading to R. solanacearum cell death caused by hydroxycoumarins. Deletion of lpxB substantially inhibited the growth of R. solanacearum, and reduced virulence of pathogen on tobacco plants.

Conculsion: Our transcriptomic analyses show that hydroxycoumarins specific suppressed genes expression involved in fatty acid synthesis, RNA modification, ribosomal submits, oxidative phosphorylation and electrontransport. These findings provide evidence that hydroxycoumarins inhibit R. solanacearum growth through affect multi-target effect. Hydroxycoumarins could serve as sustainable natural bioresources against plant bacterial wilt through membrane destruction targeting the lipopolysaccharides biosynthesis pathway. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/ps.6557DOI Listing
July 2021

Acidic Microenvironment Aggravates the Severity of Hepatic Ischemia/Reperfusion Injury by Modulating M1-Polarization Through Regulating PPAR-γ Signal.

Front Immunol 2021 21;12:697362. Epub 2021 Jun 21.

Hepatopancreatobiliary Surgery Department, The Third Affiliated Hospital of Soochow University, Changzhou First People's Hospital, Changzhou, China.

Hepatic injury induced by ischemia and reperfusion (HIRI) is a major clinical problem after liver resection or transplantation. The polarization of macrophages plays an important role in regulating the severity of hepatic ischemia/reperfusion injury. Recent evidence had indicated that the ischemia induces an acidic microenvironment by causing increased anaerobic glycolysis and accumulation of lactic acid. We hypothesize that the acidic microenvironment might cause the imbalance of intrahepatic immunity which aggravated HIRI. The hepatic ischemia/reperfusion injury model was established to investigate the effect of the acidic microenvironment to liver injury. Liposomes were used to deplete macrophages . Macrophages were cultured under low pH conditions to analyze the polarization of macrophages . Activation of the PPAR-γ signal was determined by Western blot. PPAR-γ agonist GW1929 was administrated to functionally test the role of PPAR-γ in regulating macrophage-mediated effects in the acidic microenvironment during HIRI. We demonstrate that acidic microenvironment aggravated HIRI while NaHCO reduced liver injury through neutralizing the acid, besides, liposome abolished the protective ability of NaHCO through depleting the macrophages. In vivo and vitro experiment showed that acidic microenvironment markedly promoted M1 polarization but inhibited M2 polarization of macrophage. Furthermore, the mechanistic study proved that the PPAR-γ signal was suppressed during the polarization of macrophages under pH = 6.5 culture media. The addition of PPAR-γ agonist GW1929 inhibited M1 polarization under acidic environment and reduced HIRI. Our results indicate that acidic microenvironment is a key regulator in HIRI which promoted M1 polarization of macrophages through regulating PPAR-γ. Conversely, PPAR-γ activation reduced liver injury, which provides a novel therapeutic concept to prevent HIRI.
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http://dx.doi.org/10.3389/fimmu.2021.697362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255974PMC
June 2021

Deployment of workforce in global health: what should be the priorities for China?

Glob Health Res Policy 2021 Jul 6;6(1):22. Epub 2021 Jul 6.

National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), No. 207 Ruijin Er Road, Huangpu District, Shanghai, 200025, China.

Background: China has increasingly emerged as an important player in global health. However, compared to developed countries, China still lacks a sufficient health workforce for global health engagement with the necessary competencies required. The world has recognized that to solve global health issues, the role of China needs to be strengthened. The priorities for the deployment of the Chinese workforce in global health remain unclear. This study aims to identify the priorities of the deployment of Chinese global health workforce by exploring the core competencies for Chinese global health workforce, factors influencing the deployment and the approach of deployment.

Methods: Quantitative descriptive statistical analysis was applied to analyze the quantitative data. A total of 148 key respondents from 10 provinces in China conducting global health projects over the last 3 years were selected as the study subjects. A structured questionnaire was developed to collect the data on four aspects, including general information, core competencies, factors influencing deployment, and mode of deployment. The questionnaire was distributed to the respondents through an online survey. All original data were exported to Microsoft Excel 2010 to calculate the frequencies and percentages of each option. A descriptive analysis was carried out of the priorities of deployment of the Chinese global health workforce.

Results: More than half of the respondents (51.4%, 76/148) regarded "communication" as the most important competency of the Chinese global health workforce, while a large proportion of participants from Chinese embassies (50.0%, 6/12) and international organizations (75.0%, 12/16) believed that "professional skills" were paramount. In addition, 58.1% (86/148) of the participants agreed that incentive factors (salary, professional position, etc.) were the main factors that influenced deployment, whereas 75% (12/16) of participants from international organizations emphasized "security" as the most important determinant. In addition, 60.8% (90/148) of the participants thought that the deployment of staff should be based on the needs of the global health project implementation.

Conclusions: This study highlights the deployment priorities of the Chinese global health workforce, including strengthening communication and professional skills, focusing on personal security and incentives, and catering to the project implementation. This study also highlights the importance of Chinese agencies in developing global health mindsets through global health practices and proactive integration within the global community.
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http://dx.doi.org/10.1186/s41256-021-00208-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258270PMC
July 2021

Correction to: Chromobox Homolog 4 is Correlated with Prognosis and Tumor Cell Growth in Hepatocellular Carcinoma.

Ann Surg Oncol 2021 Jul 2. Epub 2021 Jul 2.

State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China.

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http://dx.doi.org/10.1245/s10434-021-10400-8DOI Listing
July 2021

Retinex-Based Fast Algorithm for Low-Light Image Enhancement.

Entropy (Basel) 2021 Jun 13;23(6). Epub 2021 Jun 13.

School of Mechanical Engineering, Sichuan University, Chengdu 610065, China.

We proposed the Retinex-based fast algorithm (RBFA) to achieve low-light image enhancement in this paper, which can restore information that is covered by low illuminance. The proposed algorithm consists of the following parts. Firstly, we convert the low-light image from the RGB (red, green, blue) color space to the HSV (hue, saturation, value) color space and use the linear function to stretch the original gray level dynamic range of the V component. Then, we estimate the illumination image via adaptive gamma correction and use the Retinex model to achieve the brightness enhancement. After that, we further stretch the gray level dynamic range to avoid low image contrast. Finally, we design another mapping function to achieve color saturation correction and convert the enhanced image from the HSV color space to the RGB color space after which we can obtain the clear image. The experimental results show that the enhanced images with the proposed method have better qualitative and quantitative evaluations and lower computational complexity than other state-of-the-art methods.
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http://dx.doi.org/10.3390/e23060746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231777PMC
June 2021

Osteopontin isoform c promotes the survival of cisplatin-treated NSCLC cells involving NFATc2-mediated suppression on calcium-induced ROS levels.

BMC Cancer 2021 Jun 29;21(1):750. Epub 2021 Jun 29.

School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China.

Background: Tumor microenvironment (TME) critically contributed to the malignant progression of transformed cells and the chemical responses to chemotherapy reagents. Osteopontin (OPN) is a secretory onco-protein with several splicing isoforms, all of which were known to regulate tumor growth and able to alter cell-cell or cell-TME communication, however, the exact role and regulation of the OPN splicing isoforms was not well understood.

Methods: In this study, the effects of conditioned medium from the culture of OPN splicing isoforms overexpressing cells on cell functions were evaluated. The methods of nuclear calcium reporter assays and subcellular distribution of nuclear factor of activated T cells c2 (NFATc2) assays were used to investigate the molecular mechanism underlining the roles of OPN splicing isoforms.

Results: We found that the survival of NSCLC cells treated with cisplatin was increased by secretory OPNc in the condition medium, where reduction of apoptosis by OPNc was associated with the activation of cellular calcium signals and subsequent nuclear translocation of NFATc2.

Conclusions: The results revealed a mechanism of OPN and downstream signal for tumor cells to survive in chemo-stressed TME, which emphasized the importance of secretory proteins in alternative splicing isoforms. Our study not only demonstrated the importance of OPN neutralization for anti-tumor effects, but also implied that modulation in calcium/NFATc2/ROS axis could be a novel approach for improving the long-term outcome of NSCLC treatment.
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http://dx.doi.org/10.1186/s12885-021-08495-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243455PMC
June 2021

Identification of inhibitors targeting polyketide synthase 13 of Mycobacterium tuberculosis as antituberculosis drug leads.

Bioorg Chem 2021 Jun 21;114:105110. Epub 2021 Jun 21.

Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Chinese Academy of Medical Sciences Key Laboratory of Anti-DR TB Innovative Drug Research, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, 1 Xian Nong Tan Street, Beijing 100050, PR China. Electronic address:

Polyketide synthase 13 (Pks13) is an essential enzyme in the synthesis of mycolic acids in Mtb. Therefore, Pks13 is a promising drug target for tuberculosis treatment. We used a structure-guided approach to identify novel chemotype inhibitors of Pks13 and assessed them using a Pks13 enzymatic assay and surface plasmon resonance. The structure-activity relationships (SAR) results demonstrated that the substituents at the 2, 5, and 6 positions of the 4H-chromen-4-one scaffold are critical for maintaining the MIC. Compound 6e with 2-hydroxyphenyl at the 2 position of the 4H-chromen-4-one scaffold, exhibited potent activity against Mtb H37Rv (MIC = 0.45 μg/mL) and displayed good Pks13 affinity and inhibition (IC = 14.3 μM). This study described here could provide an avenue to explore a novel inhibitor class for Pks13 and aid the further development of antituberculosis drugs.
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http://dx.doi.org/10.1016/j.bioorg.2021.105110DOI Listing
June 2021

The Ongoing Unmet Needs in Chronic Lymphocytic Leukemia: TP53 Disruption, Richter, and Beyond.

Authors:
Wei Ding

Hematol Oncol Clin North Am 2021 Aug 28;35(4):739-759. Epub 2021 May 28.

Division of Hematology, Mayo Clinic, 200 First Street, Southwest, Rochester, MN 55905, USA. Electronic address:

Despite recent success in regard to targeted therapies in chronic lymphocytic leukemia (CLL), patients with TP53 disruption (including deletion and/or mutation) continue to have poor outcomes compared with other patients with CLL. In this article, a review of common TP53 mutations in CLL, and recent trials using novel targeted agents in CLL patients with TP53 disruption, is provided with the goal of emphasizing the need to continuously focus on this area of research. In addition, limited but available data on double refractory CLL to BTK inhibitor and BCL-2 inhibitor, and on Richter syndrome, are reviewed.
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http://dx.doi.org/10.1016/j.hoc.2021.04.001DOI Listing
August 2021

Post-translational Formation of Aminomalonate by a Promiscuous Peptide-modifying Radical SAM Enzyme.

Angew Chem Int Ed Engl 2021 Jun 24. Epub 2021 Jun 24.

Fudan University, Chemistry, 220 Handan Rd Yuanchengying Building 415, 200433, Shanghai, CHINA.

Aminomalonate (Ama) is a widespread structural motif in Nature, whereas its biosynthetic route is only partially understood. In this study, we show that a radical S-adenosylmethionine (rSAM) enzyme involved in cyclophane biosynthesis exhibits remarkable catalytic promiscuity. This enzyme, named three-residue cyclophane forming enzyme (3-CyFE), mainly produces cyclophane in vivo, whereas it produces formylglycine (FGly) as a major product and barely produce cyclophane in vitro. Importantly, the enzyme can further oxidize FGly to produce Ama. Bioinformatics study revealed that 3-CyFEs have evolved from a common ancestor with anaerobic sulfatase maturases (anSMEs), and possess a similar set of catalytic residues with anSMEs. Remarkably, the enzyme does not need leader peptide for activity and is fully active on a truncated peptide containing only 5 amino acids of the core sequence. Our work discloses the first ribosomal path towards Ama formation, providing a possible hint for the rich occurrence of Ama in Nature.
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http://dx.doi.org/10.1002/anie.202107192DOI Listing
June 2021

Operative treatments for osteochondral lesions of the talus in adults: A systematic review and meta-analysis.

Medicine (Baltimore) 2021 Jun;100(25):e26330

Department of Orthopedic, the 920th Hospital of Joint Logistics Support Force.

Purpose: This systematic review aimed to identify the available evidence regarding the comparative effectiveness and safety of various operative treatments in adult patients with osteochondral lesions of the talus (OLT).

Materials And Methods: The PubMed, Embase, ISI Web of Knowledge, and the Cochrane Controlled Trial Register of Controlled Trials were searched from their inception date to September 2019. Two reviewers selected the randomized controlled trials (RCTs) and non-RCTs assessing the comparative effectiveness and safety of various operative treatments for OLT. The meta-analysis was performed using Revman 5.3.

Results: Eight studies (1 RCT and 7 non-RCTs) with 375 patients were included in this review. The difference in the American Orthopaedic Foot and Ankle Society (AOFAS) score between the cartilage repair and replacement was not significant. The cartilage regeneration with or without cartilage repair had significant superiority in improving the AOFAS score compared with the cartilage repair. The difference in the magnetic resonance observation of cartilage repair tissue score between the cartilage repair and replacement and between cartilage repair and cartilage repair plus regeneration was significant.

Conclusions: Cartilage regeneration and cartilage repair plus regeneration had significant superiority in improving the ankle function and radiological evaluation of OLT, although the trials included did not have high-level evidence. Moreover, which treatment between the 2 was safer could not be addressed in this review as most of the trials did not report the safety outcome. Further studies are needed to define the best surgical option for treating OLT.
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http://dx.doi.org/10.1097/MD.0000000000026330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238309PMC
June 2021

Establishment of Rat Models of Different Pathological Types of Hypersensitivity Pneumonitis Using Pigeon Droppings.

Int Arch Allergy Immunol 2021 Jun 17:1-9. Epub 2021 Jun 17.

Department of Respiratory and Critical Care Medicine, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China.

Background: The pathogenesis and pulmonary histopathological characteristics of hypersensitivity pneumonitis (HP) are not yet fully understood. Therefore, we established animal models of HP of different stages, aiming to provide support for research on this disease.

Methods: We established rat models of pigeon breeder's lung of different pathological types by creating freeze-dried allergen powder from fresh pigeon feathers, dander, and other droppings. Freeze-dried allergen powder suspensions of pigeon droppings were used to establish 2 rat models of HP, one by aerosol inhalation and one by airway instillation, and the rats were sacrificed after different lengths of time to observe the pathological changes in their lung tissues.

Results: By the 40th week after allergen inhalation, granulomas were the main changes in the model, without fibrotic changes. When using airway instillation to establish the model, at the 20th week, group 1 (low dose + twice/week) and group 2 (medium dose + twice/week) showed granuloma changes, but no fibrosis; group 3 (high dose + once/week) and group 4 (high dose + twice/week) both showed obvious pulmonary fibrotic changes, but the death rate of rats in group 4 was greater.

Conclusions: Both aerosol inhalation and airway instillation of freeze-dried pigeon allergen powder can successfully establish an HP model. The airway instillation method can cause pulmonary fibrotic changes in a short time, and the pulmonary pathological changes of animal models manifest with an obvious time-dose effect.
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http://dx.doi.org/10.1159/000516233DOI Listing
June 2021

Site-selective aromatic C-H λ-iodanation with a cyclic iodine(iii) electrophile in solution and solid phases.

Chem Sci 2020 Jun 23;11(28):7356-7361. Epub 2020 Jun 23.

Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University Singapore 637371 Singapore

An efficient and site-selective aromatic C-H λ-iodanation reaction is achieved using benziodoxole triflate (BXT) as an electrophile under room temperature conditions. The reaction tolerates a variety of electron-rich arenes and heteroarenes to afford the corresponding arylbenziodoxoles in moderate to good yields. The reaction can also be performed mechanochemically by grinding a mixture of solid arenes and BXT under solvent-free conditions. The arylbenziodoxoles can be used for various C-C and C-heteroatom bond formations, and are also amenable to further modification by electrophilic halogenation. DFT calculations suggested that the present reaction proceeds a concerted λ-iodanation-deprotonation transition state, where the triflate anion acts as an internal base.
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http://dx.doi.org/10.1039/d0sc02737eDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159425PMC
June 2020

Visible-light excitable Eu-induced hyaluronic acid-chitosan aggregates with heterocyclic ligands for sensitive and fast recognition of hazardous ions.

Int J Biol Macromol 2021 Aug 10;184:188-199. Epub 2021 Jun 10.

Institute of Hybrid Materials, National Center of International Joint Research for Hybrid Materials Technology, National Base of International Sci. & Technology Cooperation on Hybrid Materials, Qingdao University, 308 Ningxia Road, Qingdao 266071, China. Electronic address:

Water-soluble luminescent lanthanide complexes that can be excited with visible light could enable rapid detection of toxic anions and cations in biological systems. Eu-induced hyaluronic acid-chitosan aggregates (EIHCA) can improve the stability, biocompatibility, efficiency, and light absorption of luminescent Eu complexes. Visible-range excitation may avoid phototoxicity associated with overexposure to UV light in biological and ecological applications. In this work, we synthesized and characterized series of EIHCA complexes having three N-donor heterocyclic ligands: 2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline (Dphen), 2,2': 6',2″-terpyridine (Tpy) and 1,10-phenanthroline monohydrate (Phen). These complexes possessed bright red fluorescence with a visible range excitation maximum. The photophysical properties of one formulation (we denote as EDL6) include fast quenching response (20 s) of the fluorescence, multi-selectivity, low limit of detection, and high quenching (K) values, enabling selective, rapid and sensitive recognition of CrO and Fe in aqueous solution. Furthermore, EDL6 exhibits cytocompatibility with mammalian cells that make these complexes promising biocompatible candidate as a safe replacement of organic fluorophores for fluorescence sensing applications. Thus, these new EIHCA complexes were successfully employed for the selective detection of hazardous materials in biological and aqueous environment samples.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.06.051DOI Listing
August 2021

Association of ERBB4 genetic polymorphism with the risk and prognosis of non-small cell lung cancer in Chinese Han population: A population-based case-control study.

Medicine (Baltimore) 2021 May;100(19):e25762

Department of Respiratory and Critical Care Medicine, Changzhi People's Hospital, Shanxi Province, China.

Abstract: The aim of this study was to explore the association of rs1836724 single-nucleotide polymorphism (SNP) of ERBB4 with risk and prognosis of non-small cell lung cancer (NSCLC) in the Chinese Han population.The genotype of rs1836724 SNP of ERBB4 from 258 patients with NSCLC and 200 noncancer controls were detected the TaqMan-MGB probes real-time fluorescence polymerase chain reaction. The distribution of genotype and alleles between the 2 groups was compared, and the association between clinicopathological characteristic and rs1836724 SNP was analyzed. Prognosis and influencing factors were analyzed by Kaplan-Meier and Cox regression analysis.There were significant differences in the genotype and allele distribution of ERBB4 rs1836724 between the NSCLC group and control group (P < .05). And CC genotype of rs1836724 was associated with increased risk of NSCLC in the Chinese Han population. Rs1836724 SNP was associated with TNM stage and lymph nodal metastasis (P = .001, P = .007). The median follow-up was 29 months, and the progression-free survival and overall survival of 258 NSCLC patients were 27.91% and 31.39%, respectively. Patients with GG genotype of rs1836724 had poor progression-free survival and overall survival. Rs1836724 SNP was an independent prognostic marker of NSCLC patients, CC genotype had a high risk of poor prognosis (odds ratio = 1.587, 95% confidence interval: 1.079-2.335, P = .019).In Chinese Han populations, rs1836724 SNP of ERBB4 may contribute toward the increased risk and poor prognosis of NSCLC.
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http://dx.doi.org/10.1097/MD.0000000000025762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133196PMC
May 2021

Current Advancements in Sactipeptide Natural Products.

Front Chem 2021 20;9:595991. Epub 2021 May 20.

State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a growing class of natural products that benefited from genome sequencing technology in the past two decades. RiPPs are widely distributed in nature and show diverse chemical structures and rich biological activities. Despite the various structural characteristic of RiPPs, they follow a common biosynthetic logic: a precursor peptide containing an N-terminal leader peptide and a C-terminal core peptide; in some cases,a follower peptide is after the core peptide. The precursor peptide undergoes a series of modification, transport, and cleavage steps to form a mature natural product with specific activities. Sactipeptides (Sulfur-to-alpha carbon thioether cross-linked peptides) belong to RiPPs that show various biological activities such as antibacterial, spermicidal and hemolytic properties. Their common hallmark is an intramolecular thioether bond that crosslinks the sulfur atom of a cysteine residue to the α-carbon of an acceptor amino acid, which is catalyzed by a rSAM enzyme. This review summarizes recent achievements concerning the discovery, distribution, structural elucidation, biosynthesis and application prospects of sactipeptides.
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http://dx.doi.org/10.3389/fchem.2021.595991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172795PMC
May 2021

, Encoding a Putative RBR E3 Ligase Protein of , Plays an Important Role in the Regulation of Resistance to Infection.

Int J Mol Sci 2021 May 24;22(11). Epub 2021 May 24.

College of Plant Protection, Southwest University, Chongqing 400715, China.

E3 ubiquitin ligases, the most important part of the ubiquitination process, participate in various processes of plant immune response. RBR E3 ligase is one of the E3 family members, but its functions in plant immunity are still little known. NtRNF217 is a RBR E3 ligase in tobacco based on the sequence analysis. To assess roles of in tobacco responding to , overexpression experiments in (Yunyan 87, a susceptible cultivar) were performed. The results illuminated that -overexpressed tobacco significantly reduced multiplication of and inhibited the development of disease symptoms compared with wild-type plants. The accumulation of HO and O in -OE plants was significantly higher than that in WT-Yunyan87 plants after pathogen inoculation. The activities of CAT and SOD also increased rapidly in a short time after inoculation in -OE plants. What is more, overexpression of enhanced the transcript levels of defense-related marker genes, such as , , , , and in -OE plants after inoculation. The results suggested that played an important role in regulating the expression of defense-related genes and the antioxidant enzymes, which resulted in resistance to infection.
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http://dx.doi.org/10.3390/ijms22115507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8197134PMC
May 2021

NLRP3 Deletion Attenuated Angiotensin II-Induced Renal Fibrosis by Improving Mitochondrial Dysfunction and Endoplasmic Reticulum Stress.

Nephron 2021 Jun 1:1-10. Epub 2021 Jun 1.

Division of Nephrology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

Background: Increasing evidence suggests that angiotensin II (Ang II), the bioactive pro-oxidant in the renin-angiotensin system, aggravates fibrosis, and the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is involved in multiple diseases, such as renal fibrosis. However, the role and underlying mechanism of Ang II in renal fibrosis remain unclear. Here, we investigated whether the NLRP3 inflammasome mediated Ang II-induced renal fibrosis, as well as the downstream pathways involved in this process.

Methods: NLRP3-/- mice were used as a model to study Ang II-infused renal fibrosis. Mice were divided into 4 groups: sham wild type, Ang II-infused wild type, sham NLRP3-/-, and Ang II-infused NLRP3-/- groups. Ang II infusion-induced renal injury was confirmed by periodic acid-Schiff and Masson's staining, immunohistochemistry, and transmission electron microscopy (TEM). Mitochondrial morphology was presented on TEM micrographs, and mitochondrial function was reflected by the protein levels of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), mitochondrial transcription factor A (TFAM), dynamin-related protein 1 (DRP1), and mitofusin 2 (MFN2), as assessed by Western blotting. Endoplasmic reticulum (ER) stress was characterized by changes in the levels of ER chaperones, such as GRP94, BiP, CHOP, and caspase 12.

Results: Ang II infusion increased cell proliferation, extracellular matrix overproduction, inflammatory cell infiltration, and glomerulosclerosis and induced obvious morphological abnormalities in podocytes. Ang II infusion promoted mitochondrial damage, as indicated by TEM, and induced mitochondrial dysfunction, as evidenced by downregulation of PGC-1α, TFAM, and increased mitochondrial ROS. In addition, DRP1 expression was upregulated, while MFN2 expression was markedly decreased. The levels of GRP94, BiP, CHOP, and caspase 12 were significantly increased. However, all these detrimental effects were attenuated by NLRP3 deletion.

Conclusions: NLRP3 deletion may attenuate angiotensin II-induced renal fibrosis by improving mitochondrial dysfunction and ER stress.
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http://dx.doi.org/10.1159/000513739DOI Listing
June 2021

Magneto-Revealing and Acceleration of Hidden Kirkendall Effect in Galvanic Replacement Reaction.

J Phys Chem Lett 2021 Jun 1;12(22):5294-5300. Epub 2021 Jun 1.

Anhui Key Laboratory of Condensed Matter Physics at Extreme Conditions, High Magnetic Field Laboratory, HFIPS, Anhui, Chinese Academy of Sciences, Hefei, 230031, China.

Rate and product control are crucial for a chemical process and are useful in a wide range of applications. Traditionally, thermodynamic parameters, such as temperature or pressure, have been used to control the chemical reactions. Here, by using the fabrication of a hollow MnFeO nanostructure as a model system, we report an experimental tuning of both chemical reaction rate and product by a high magnetic field. A 12 times magneto-acceleration of the galvanic replacement (GR) reaction was observed. Moreover, it is first demonstrated that a magnetic field can unravel and accelerate the hidden Kirkendall effect (KE) in addition to the pristine GR reaction. With coaction of magneto-tuned KE and GR, not only the rate but also the composition as well as magnetic property of the products could be modulated. These observations suggest that not only is a magnetic field a variable parameter that cannot be ignored, but also it can effectively control both rate and product in a chemical reaction, which provides a new route for chemical process controlling and shape/composition designing in material synthesis.
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http://dx.doi.org/10.1021/acs.jpclett.1c01327DOI Listing
June 2021

EYA2 suppresses the progression of hepatocellular carcinoma via SOCS3-mediated blockade of JAK/STAT signaling.

Mol Cancer 2021 05 27;20(1):79. Epub 2021 May 27.

National Translational Science Center for Molecular Medicine, Department of Cell Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an, 710032, China.

Background: Somatic mutations are involved in hepatocellular carcinoma (HCC) progression, but the genetic mechanism associated to hepatocarcinogenesis remains poorly understood. We report that Eyes absent homolog 2 (EYA2) suppresses the HCC progression, while EYA2(A510E) mutation identified by exome sequencing attenuates the tumor-inhibiting effect of EYA2.

Methods: Whole-exome sequencing was performed on six pairs of human HCC primary tumors and matched adjacent tissues. Focusing on EYA2, expression level of EYA2 in human HCC samples was evaluated by quantitative real-time PCR, western blot and immunohistochemistry. Loss- and gain-of-function studies, hepatocyte-specific deletion of EYA2 (Eya2) in mice and RNA sequencing analysis were used to explore the functional effect and mechanism of EYA2 on HCC cell growth and metastasis. EYA2 methylation status was evaluated using Sequenom MassARRAY and publicly available data analysis.

Results: A new somatic mutation p.Ala510Glu of EYA2 was identified in HCC tissues. The expression of EYA2 was down-regulated in HCC and associated with tumor size (P = 0.001), Barcelona Clinic Liver Cancer stage (P = 0.016) and tumor differentiation (P = 0.048). High level of EYA2 was correlated with a favorable prognosis in HCC patients (P = 0.003). Results from loss-of-function and gain-of-function experiments suggested that knockdown of EYA2 enhanced, while overexpression of EYA2 attenuated, the proliferation, clone formation, invasion, and migration of HCC cells in vitro. Delivery of EYA2 gene had a therapeutic effect on inhibition of orthotopic liver tumor in nude mice. However, EYA2(A510E) mutation led to protein degradation by unfolded protein response, thus weakening the inhibitory function of EYA2. Hepatocyte-specific deletion of EYA2 in mice dramatically promoted diethylnitrosamine-induced HCC development. EYA2 was also down-regulated in HCC by aberrant CpG methylation. Mechanically, EYA2 combined with DACH1 to transcriptionally regulate SOCS3 expression, thus suppressing the progression of HCC via SOCS3-mediated blockade of the JAK/STAT signaling pathway.

Conclusions: In our study, we identified and validated EYA2 as a tumor suppressor gene in HCC, providing a new insight into HCC pathogenesis.
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http://dx.doi.org/10.1186/s12943-021-01377-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157759PMC
May 2021

Regional Brain Glucose Metabolism and Its Prognostic Value in Pretreatment Extranodal Natural Killer/T-Cell Lymphoma Patients.

Onco Targets Ther 2021 14;14:3179-3191. Epub 2021 May 14.

Department of Nuclear Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, People's Republic of China.

Objective: To explore regional brain glucose metabolic abnormalities of pretreatment stage I/II extranodal natural killer/T-cell lymphoma (ENKTL) patients using positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose integrated with computed tomography (F-FDG PET/CT) and assess its prognostic value.

Methods: Sixty pretreatment stage I/II ENKTL patients were enrolled in this retrospective study and divided into survival (n = 45) and death (n = 15) groups according to their status at the end of follow-up. A control group consisted of 60 healthy subjects. Regional cerebral glucose metabolism was evaluated on a voxel-by-voxel basis using statistical parametric mapping (SPM8) under a certain significance level (P < 0. 001) and voxel threshold (K = 100 voxels).

Results: Decreased metabolism was noted in patients, involving the bilateral prefrontal and orbitofrontal cortex, partial parietal and occipital cortex, cingulate gyrus and cerebellum; the sensorimotor cortex was largely spared. Increased metabolism was observed in the bilateral putamen, amygdala, and parahippocampal gyrus. Compared with the survival group, the death group had higher metabolism in the bilateral amygdala, putamen, left thalamus, uncus, and parahippocampal gyrus. Only B symptoms were associated with the increased metabolism of basal ganglia and thalamus (BGT). Patients with high metabolic tumor volume, total lesion glycolysis (TLG) and BGT metabolism had a poor prognosis. TLG and maximum standardized uptake value (SUVmax) LBGT/SUVmaxRight cerebellum were associated with Eastern Cooperative Oncology Group (ECOG) and prognostic index of natural killer lymphoma and Epstein-Barr virus-DNA (PINKE) scores. In multivariate analysis, only ECOG was an independent prognostic factor of both progression-free survival (PFS) and overall survival (OS). PINKE was an independent prognostic factor of OS.

Conclusion: Pretreatment stage I/II ENKTL patients exhibited abnormal regional cerebral glucose metabolism. Higher pretreatment glucose metabolism in BGT could predict a relatively poor prognosis but did not surpass the predictive values of ECOG and PINKE in stage I/II ENKTL patients.
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http://dx.doi.org/10.2147/OTT.S308872DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131093PMC
May 2021

MRI Screening and MRI/US Fusion-Guided Transperineal Biopsy in Detecting Prostate Cancer.

Technol Cancer Res Treat 2021 Jan-Dec;20:15330338211019418

Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.

Objective: Systematic biopsy plays a vital role in diagnosing prostate cancer, but it can lead to misdiagnoses or undertreatment. Advances in magnetic resonance imaging (MRI) and its guided targeting technology provide the possibility of improving the use of biopsies. This study aimed to evaluate the performance of MRI screening and MRI/ultrasound (MRI/US) fusion-guided transperineal biopsy in the detection of prostate cancer.

Methods: We performed a retrospective study on patients with suspected prostate cancer in the Kunshan Hospital Affiliated with Jiangsu University from January 2017 to December 2019. All of the patients underwent MRI examinations, followed by a systematic biopsy (either alone or in combination with MRI/US fusion-guided targeted biopsy, based on MRI-visible lesions). We evaluated the diagnostic accuracy of MRI screening and compared biopsy methods by considering sensitivity, specificity, and area under the curve (AUC) values.

Results: A total of 157 patients were enrolled, including 112 patients with MRI-visible lesions and 45 patients without MRI-visible lesions. The cancer detection rate (CDR) was higher in patients with MRI-visible lesions ( < 0.001); however, the serum prostate-specific antigen (PSA) indicators were similar ( > 0.05). The AUC of MRI was 0.63, which was superior to the AUC values of ultrasound (AUC = 0.55, = 0.031) and digital rectal examination (AUC = 0.52, = 0.041) for screening prostate cancer. Both overall CDR and clinically significant prostate cancer detection rates were improved if we combined systematic biopsy and MRI/US fusion-guided targeted biopsy procedures.

Conclusion: Overall, prior MRI screening may serve as a classifier for avoiding the overuse of biopsies. A combination of systematic and MRI/US fusion-guided targeted biopsy procedures offers an optimal regimen for detecting prostate cancer.
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http://dx.doi.org/10.1177/15330338211019418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8142015PMC
May 2021

LncRNA DANCR improves the dysfunction of the intestinal barrier and alleviates epithelial injury by targeting the miR-1306-5p/PLK1 axis in sepsis.

Cell Biol Int 2021 May 18. Epub 2021 May 18.

Department of Burn and Plastic Surgery, Yijishan Hospital, The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, China.

Intestinal barrier dysfunction often occurs in various acute or chronic pathological conditions and has been identified as an important clinical problem. Herein, we explored the biological role and molecular mechanism of Polo-like kinase 1 (PLK1) and differentiation antagonizing non-protein coding RNA (DANCR) in intestinal barrier dysfunction caused by sepsis. RT-qPCR analysis was used to examine PLK1, miR-1306-5p, and DANCR expression in NCM460 cells after LPS treatment. TUNEL assay and Western blot analysis were performed to explore PLK1 function in cell apoptosis and intestinal barrier in vitro. Hematoxylin and eosin staining, Western blot analysis, and TUNEL assay were used to investigate DANCR function in the intestinal barrier and cell apoptosis in vivo. The interaction between miR-1306-5p and PLK1 (or DANCR) was validated by luciferase reporter assay. As a result, PLK1 overexpression decreased cell apoptosis and promoted intestinal barrier function. Moreover, DANCR was validated as a sponge of miR-1306-5p to target PLK1. In addition, we found that DANCR overexpression decreased intestinal mucosal permeability and colon mucosa epithelial cell apoptosis in vivo. Conclusively, DANCR improved intestinal barrier dysfunction and alleviated epithelial injury by targeting the miR-1306-5p/PLK1 axis in sepsis.
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http://dx.doi.org/10.1002/cbin.11633DOI Listing
May 2021

Safety and efficacy of meplazumab in healthy volunteers and COVID-19 patients: a randomized phase 1 and an exploratory phase 2 trial.

Signal Transduct Target Ther 2021 05 17;6(1):194. Epub 2021 May 17.

Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

Recent evidence suggests that CD147 serves as a novel receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Blocking CD147 via anti-CD147 antibody could suppress the in vitro SARS-CoV-2 replication. Meplazumab is a humanized anti-CD147 IgG monoclonal antibody, which may effectively prevent SARS-CoV-2 infection in coronavirus disease 2019 (COVID-19) patients. Here, we conducted a randomized, double-blinded, placebo-controlled phase 1 trial to evaluate the safety, tolerability, and pharmacokinetics of meplazumab in healthy subjects, and an open-labeled, concurrent controlled add-on exploratory phase 2 study to determine the efficacy in COVID-19 patients. In phase 1 study, 59 subjects were enrolled and assigned to eight cohorts, and no serious treatment-emergent adverse event (TEAE) or TEAE grade ≥3 was observed. The serum and peripheral blood C and area under the curve showed non-linear pharmacokinetic characteristics. No obvious relation between the incidence or titer of positive anti-drug antibody and dosage was observed in each cohort. The biodistribution study indicated that meplazumab reached lung tissue and maintained >14 days stable with the lung tissue/cardiac blood-pool ratio ranging from 0.41 to 0.32. In the exploratory phase 2 study, 17 COVID-19 patients were enrolled, and 11 hospitalized patients were involved as concurrent control. The meplazumab treatment significantly improved the discharged (P = 0.005) and case severity (P = 0.021), and reduced the time to virus negative (P = 0.045) in comparison to the control group. These results show a sound safety and tolerance of meplazumab in healthy volunteers and suggest that meplazumab could accelerate the recovery of patients from COVID-19 pneumonia with a favorable safety profile.
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http://dx.doi.org/10.1038/s41392-021-00603-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127508PMC
May 2021

Enhancement of Migration and Tenogenic Differentiation of Macaca Mulatta Tendon-Derived Stem Cells by Decellularized Tendon Hydrogel.

Front Cell Dev Biol 2021 27;9:651583. Epub 2021 Apr 27.

Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China.

Decellularized tendon hydrogel from human or porcine tendon has been manufactured and found to be capable of augmenting tendon repair . However, no studies have clarified the effect of decellularized tendon hydrogel upon stem cell behavior. In the present study, we developed a new decellularized tendon hydrogel (T-gel) from Macaca mulatta, and investigated the effect of T-gel on the proliferation, migration and tenogenic differentiation of Macaca mulatta tendon-derived stem cells (mTDSCs). The mTDSCs were first identified to have universal stem cell characteristics, including clonogenicity, expression of mesenchymal stem cell and embryonic stem cell markers, and multilineage differentiation potential. Decellularization of Macaca mulatta Achilles tendons was confirmed to be effective by histological staining and DNA quantification. The resultant T-gel exhibited highly porous structure or similar nanofibrous structure and approximately swelling ratio compared to the collagen gel (C-gel). Interestingly, stromal cell-derived factor-1 (SDF-1) and fibromodulin (Fmod) inherent in the native tendon extracellular matrix (ECM) microenvironment were retained and the values of SDF-1 and Fmod in the T-gel were significantly higher than those found in the C-gel. Compared with the C-gel, the T-gel was found to be cytocompatible with NIH-3T3 fibroblasts and displayed good histocompatibility when implanted into rat subcutaneous tissue. More importantly, it was demonstrated that the T-gel supported the proliferation of mTDSCs and significantly promoted the migration and tenogenic differentiation of mTDSCs compared to the C-gel. These findings indicated that the T-gel, with its retained nanofibrous structure and some bioactive factors of native tendon ECM microenvironment, represents a promising hydrogel for tendon regeneration.
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http://dx.doi.org/10.3389/fcell.2021.651583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111289PMC
April 2021

Image reconstruction with the chaotic fiber laser in scattering media.

Appl Opt 2021 May;60(13):4004-4012

The reconstruction of the size, position, optical properties, and structure of the object in scattering media was realized with a chaotic fiber laser. The light from the chaotic fiber laser was split into two parts. One part was used as the detection signal to detect the object, and the other was used as the reference signal; then, the two signals were cross correlated. The attenuation of light in scattering media was attributed to scattering and absorption. The theoretical model of the peak value of cross correlation of the chaotic signals as projection data were established by the attenuation law, and the filtered back-projection algorithms were used to realize the image reconstruction. The mean squared error, the normalized mean squared error, the peak signal-to-noise ratio, and the structural similarity index of the reconstructed image were analyzed. The results show that the high resolution of the reconstructed image benefits from the high signal-to-noise ratio with the chaotic fiber laser based on a delta-like cross-correlation function.
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http://dx.doi.org/10.1364/AO.420441DOI Listing
May 2021

Distinct immune signatures in chronic lymphocytic leukemia and Richter syndrome.

Blood Cancer J 2021 May 10;11(5):86. Epub 2021 May 10.

Division of Hematology, Mayo Clinic, Rochester, MN, USA.

Richter syndrome (RS) refers to transformation of chronic lymphocytic leukemia (CLL) to an aggressive lymphoma, most commonly diffuse large B-cell lymphoma. RS is known to be associated with a number of genetic alterations such as TP53 and NOTCH1 mutations. However, it is unclear what immune microenvironment changes are associated with RS. In this study, we analyzed expression of immune checkpoint molecules and infiltration of immune cells in nodal samples, and peripheral blood T-cell diversity in 33 CLL and 37 RS patients. Compared to CLL, RS nodal tissue had higher PD-L1 expression in histiocytes and dendritic cells (median 16.6% vs. 2.8%, P < 0.01) and PD1 expression in neoplastic B cells (median 26.0% vs. 6.2%, P < 0.01), and higher infiltration of FOXP3-positive T cells (median 1.7% vs. 0.4%, P < 0.01) and CD163-positive macrophages (median 23.4% vs. 9.1%, P < 0.01). In addition, peripheral blood T-cell receptor clonality was significantly lower in RS vs. CLL patients (median [25th-75th], 0.107 [0.070-0.209] vs. 0.233 [0.111-0.406], P = 0.046), suggesting that T cells in RS patients were significantly more diverse than in CLL patients. Collectively these data suggest that CLL and RS have distinct immune signatures. Better understanding of the immune microenvironment is essential to improve immunotherapy efficacy in CLL and RS.
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http://dx.doi.org/10.1038/s41408-021-00477-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110984PMC
May 2021

Erectile Dysfunction in Type-2 Diabetes Mellitus Patients: Predictors of Early Detection and Treatment.

Urol Int 2021 May 5:1-7. Epub 2021 May 5.

Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Purpose: To identify risk factors and potential predictors of erectile dysfunction (ED) in type-2 diabetes mellitus (T2DM) patients for early detection and treatment.

Methods: A retrospective cohort was used to assess the clinical data of 105 diabetic patients with ED from May 2019 to April 2020 age-matched to 105 diabetic patients without ED. Potential risk factors that could contribute to ED were compared between the groups. Erectile function was evaluated using the International Index of Erectile Function-5 questionnaire.

Results: There were higher rates of diabetic peripheral neuropathy (p = 0.036) and retinopathy (p < 0.001), longer duration of diabetes (p < 0.001), lower estimated glomerular filtration rate (p = 0.010) values, and higher uric acid (p < 0.001) and C-reactive protein (p = 0.001) levels in the ED group compared to the non-ED group. Multivariate logistic analysis identified uric acid, diabetic retinopathy, and T2DM course as independent predictors of diabetic ED. Diabetics with retinopathy and T2DM for ≥49 months were 3.028 and 3.860 times more likely to have ED, respectively. Uric acid values ≥392.5 μmol/L were associated with 18.638 times greater risk of having ED, though the values were within normal range.

Conclusion: In T2DM patients, higher uric acid (≥392.5 μmol/L), longer diabetes duration (≥49 months), and the presence of diabetic retinopathy were important and reliable predictors for diabetic ED. For patients who have high risk factors for developing ED, diligent screening and early treatment are necessary.
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http://dx.doi.org/10.1159/000514700DOI Listing
May 2021
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