Publications by authors named "Ruifeng Wang"

89 Publications

Design, synthesis, biological evaluation and pharmacophore model analysis of novel tetrahydropyrrolo[3,4-c]pyrazol derivatives as potential TRKs inhibitors.

Eur J Med Chem 2021 Jun 15;223:113627. Epub 2021 Jun 15.

Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang, 110016, PR China.

The tropomyosin receptor kinases TRKs are responsible for different tumor types which caused by NTRK gene fusion, and have been identified as a successful target for anticancer therapeutics. Herein, we report a potent and selectivity TRKs inhibitor 19m through rational drug design strategy from a micromolar potency hit 17a. Compound 19m significantly inhibits the proliferation of TRK-dependent cell lines (Km-12), while it has no inhibitory effect on TRK-independent cell lines (A549 and THLE-2). Furthermore, kinases selectivity profiling showed that in addition to TRKs, compound 19m only displayed relatively strong inhibitory activity on ALK. These data may indicate that compound 19m has a good drug safety. Partial ADME properties were evaluated in vitro and in vivo. Compound 19m exhibited a good AUC values and volume of distribution and low clearance in the pharmacokinetics experiment of rats. Finally, a pharmacophore model guided by experimental results is proposed. We hope this theoretical model can help researchers find type I TRK inhibitors more efficiently.
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http://dx.doi.org/10.1016/j.ejmech.2021.113627DOI Listing
June 2021

Conventional Type 1 Dendritic Cells (cDC1) in Human Kidney Diseases: Clinico-Pathological Correlations.

Front Immunol 2021 12;12:635212. Epub 2021 May 12.

School of Medicine, The University of Sydney, Camperdown, NSW, Australia.

Background: cDC1 is a subset of conventional DCs, whose most recognized function is cross-presentation to CD8 T cells. We conducted this study to investigate the number and location of cDC1s in various human kidney diseases as well as their correlation with clinico-pathological features and CD8 T cells.

Methods: We analyzed 135 kidney biopsies samples. Kidney diseases included: acute tubular necrosis (ATN), acute interstitial nephritis (AIN), proliferative glomerulonephritis (GN) (IgA nephropathy, lupus nephritis, pauci-immune GN, anti-GBM disease), non-proliferative GN (minimal change disease, membranous nephropathy) and diabetic nephropathy. Indirect immunofluorescence staining was used to quantify cDC1s, CD1c DCs, and CD8 T cells.

Results: cDC1s were rarely present in normal kidneys. Their number increased significantly in ATN and proliferative GN, proportionally much more than CD1c DCs. cDC1s were mainly found in the interstitium, except in lupus nephritis, pauci-immune GN and anti-GBM disease, where they were prominent in glomeruli and peri-glomerular regions. The number of cDC1s correlated with disease severity in ATN, number of crescents in pauci-immune GN, interstitial fibrosis in IgA nephropathy and lupus nephritis, as well as prognosis in IgA nephropathy. The number of CD8 T cells also increased significantly in these conditions and cDC1 number correlated with CD8 T cell number in lupus nephritis and pauci-immune GN, with many of them closely co-localized.

Conclusions: cDC1 number correlated with various clinic-pathological features and prognosis reflecting a possible role in these conditions. Their association with CD8 T cells suggests a combined mechanism in keeping with the results in animal models.
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http://dx.doi.org/10.3389/fimmu.2021.635212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149958PMC
May 2021

Long non-coding RNA XIST promotes retinoblastoma cell proliferation, migration, and invasion by modulating microRNA-191-5p/brain derived neurotrophic factor.

Bioengineered 2021 12;12(1):1587-1598

Department of ophtalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

Long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) is oncogenic in multiple cancers. Herein, the present study is aimed at delving into how XIST functions in retinoblastoma (RB) and investigating its underlying mechanism. In this study, XIST, miR-191-5p, BDNF mRNA, and BDNF expression levels in RB tissues or cell lines were examined by quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot. The models of gain-of-function and loss-of-function were established by the transfection of pcDNA3.1-XIST, XIST siRNA, and miR-191-5p mimics and inhibitors into SO-Rb50 and Y79 cells, respectively. RB cell proliferation, migration, invasion, and apoptosis were detected employing cell counting kit-8 (CCK-8), Transwell, and terminal deoxynucleotidyl transferased UTP nick end labeling (TUNEL) assays. The regulatory relationships among XIST, miR-191-5p, and BDNF were affirmed utilizing bioinformatics analysis, luciferase reporter assay, qRT-PCR, as well as Western blot. We reported that, XIST expression was markedly elevated in RB tissue and RB cells. XIST overexpression accelerated RB cell proliferation, migration, and invasion, and attenuated RB cell apoptosis but miR-191-5p exerted the opposite effects. Besides, BDNF expression was inhibited by miR-191-5p in both mRNA and protein levels. XIST indirectly improved BDNF expression by repressing miR-191-5p expression as a competitive endogenous RNA. In conclusion, XIST expression is abnormally elevated in RB tissues and XIST can modulate proliferation, migration, invasion, and apoptosis of RB cells by regulating miR-191-5p/BDNF axis.
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http://dx.doi.org/10.1080/21655979.2021.1918991DOI Listing
December 2021

Hypertriglyceridemia Acute Pancreatitis: Animal Experiment Research.

Dig Dis Sci 2021 May 3. Epub 2021 May 3.

Department of Gastroenterology, Peking Union Medical College Hospital and Chinese Academy of Medical Sciences, Beijing, China.

In recent years, the number of acute pancreatitis cases caused by hypertriglyceridemia has increased gradually, which has caught the attention of the medical community. However, because the exact mechanism of hypertriglyceridemic acute pancreatitis (HTG-AP) is not clear, treatment and prevention in clinical practice face enormous challenges. Animal models are useful for elucidating the pathogenesis of diseases and developing and testing novel interventions. Therefore, animal experiments have become the key research means for us to understand and treat this disease. We searched almost all HTG-AP animal models by collecting many studies and finally collated common animals such as rats, mice and included some rare animals that are not commonly used, summarizing the methods to model spontaneous pancreatitis and induce pancreatitis. We sorted them on the basis of three aspects, including the selection of different animals, analyzed the characteristics of different animals, different approaches to establish hypertriglyceridemic pancreatitis and their relative advantages and disadvantages, and introduced the applications of these models in studies of pathogenesis and drug therapy. We hope this review can provide relevant comparisons and analyses for researchers who intend to carry out animal experiments and will help researchers to select and establish more suitable animal experimental models according to their own experimental design.
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http://dx.doi.org/10.1007/s10620-021-06928-0DOI Listing
May 2021

Slow viral propagation during initial phase of infection leads to viral persistence in mice.

Commun Biol 2021 Apr 29;4(1):508. Epub 2021 Apr 29.

Department of Molecular Medicine II, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.

Immune evasion of pathogens can modify the course of infection and impact viral persistence and pathology. Here, using different strains of the lymphocytic choriomeningitis virus (LCMV) model system, we show that slower propagation results in limited type I interferon (IFN-I) production and viral persistence. Specifically, cells infected with LCMV-Docile exhibited reduced viral replication when compared to LCMV-WE and as a consequence, infection with LCMV-Docile resulted in reduced activation of bone marrow derived dendritic cells (BMDCs) and IFN-I production in vitro in comparison with LCMV-WE. In vivo, we observed a reduction of IFN-I, T cell exhaustion and viral persistence following infection of LCMV-Docile but not LCMV-WE. Mechanistically, block of intracellular protein transport uncovered reduced propagation of LCMV-Docile when compared to LCMV-WE. This reduced propagation was critical in blunting the activation of the innate and adaptive immune system. When mice were simultaneously infected with LCMV-Docile and LCMV-WE, immune function was restored and IFN-I production, T cell effector functions as well as viral loads were similar to that of mice infected with LCMV-WE alone. Taken together, this study suggests that reduced viral propagation can result in immune evasion and viral persistence.
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http://dx.doi.org/10.1038/s42003-021-02028-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084999PMC
April 2021

FASDQ: Fault-Tolerant Adaptive Scheduling with Dynamic QoS-Awareness in Edge Containers for Delay-Sensitive Tasks.

Sensors (Basel) 2021 Apr 23;21(9). Epub 2021 Apr 23.

School of Computer and Electronic Information, Guangxi University, Nanning 530004, China.

As the requirement for real-time data analysis increases, edge computing is being implemented to leverage the resources of edge devices to reduce system response times and decrease the latency. However, due to the resource constraints of edge clouds, edge servers are more prone to failures than other systems. Therefore, guaranteeing the reliability of services in edge clouds is critical. In this paper, we propose a fault-tolerant adaptive scheduling mechanism with dynamic quality of service (QoS) awareness (FASDQ), which extends the primary/backup (PB) model by applying QoS on demand to task copies. The aim of the method is to reduce the latency and achieve reliable service for tasks by changing the execution time of task copies. This paper also proposes a container resource-adaptive adjustment mechanism, which adjusts the timing of resources when the available resources cannot meet the task copy requirements. Finally, this paper reports the results of simulation experiments on the EdgeCloudSim platform to evaluate the difference in performance between FASDQ and other methods. The results show that the mechanism effectively reduces the execution time of task copies and outperforms other methods in terms of reliability and general resource utilization.
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http://dx.doi.org/10.3390/s21092973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123019PMC
April 2021

Galloyl Group in B-type Proanthocyanidin Dimers Was Responsible for Its Differential Inhibitory Activity on 3T3-L1 Preadipocytes due to the Strong Lipid Raft-Perturbing Potency.

J Agric Food Chem 2021 May 23;69(17):5216-5225. Epub 2021 Apr 23.

College of Food Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, China.

The effects of three B-type proanthocyanidin (PA) dimers covering procyanidin B2 (B-0g), procyanidin B2 3'-O-gallate (B-1g), and procyanidin B2 3,3'-di-O-gallate (B-2g) on 3T3-L1 preadipocyte differentiation and the underlying mechanisms were investigated. The results showed that digalloylated B-type PA dimers (B-2g) strongly inhibited 3T3-L1 preadipocyte differentiation through disrupting the integrity of the lipid raft structure and inhibiting the expression of peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (C/EBPα) and then downregulating the expression of acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) factors, followed by B-1g, while B-0g had little effect. The different inhibitory effects were mainly due to the difference in the B-type PA dimer structure and the ability to interfere with lipid rafts. The greater the galloylation degree of B-type PA dimers, the stronger the ability to disrupt the lipid raft structure and oppose 3T3-L1 preadipocyte differentiation. In addition, galloylated B-type PA dimers had greater molecular hydrophobicity and topological polarity surface area and could penetrate into the lipid rafts to form multiple hydrogen bonds with the rafts by molecular dynamics simulation. These findings highlighted that the strong lipid raft-perturbing potency of galloylated B-type PA dimers was responsible for inhibition of 3T3-L1 preadipocyte differentiation.
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http://dx.doi.org/10.1021/acs.jafc.1c00364DOI Listing
May 2021

En bloc resection and reconstruction of a huge chondrosarcoma involving multilevel upper thoracic spine and chest wall: case report.

BMC Musculoskelet Disord 2021 Apr 12;22(1):348. Epub 2021 Apr 12.

Musculoskeletal Tumor Center, Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, China.

Background: En bloc resection of malignant tumors involving upper thoracic spine is technically difficult. We surgically treated a patient with grade 2 chondrosarcoma involving T1-5, left upper thoracic cavity, and chest wall.

Case Presentation: A 37 years old, male patient was referred to our hospital for a huge lump involved left shoulder and chest wall. In order to achieve satisfied surgical margins, anterior approach, posterior approach, and lateral approach were carried out sequentially. After en bloc tumor resection, the upper thoracic spine was reconstructed with a 3D-printed modular vertebral prosthesis, and the huge chest wall defect was repaired by a methyl methacrylate layer between 2 pieces of polypropylene mesh. Postoperatively, the patient suffered from pneumonia and neurological deterioration which fully recovered eventfully. At 24 months after operation, the vertebral prosthesis and internal fixation were intact; there was no tumor local recurrence, and the patient was alive with stable pulmonary metastases.

Conclusion: This case report describes resection of a huge chondrosarcoma involving not only multilevel upper thoracic spine, but also entire left upper thoracic cavity and chest wall. Although with complications, en bloc tumor resection with combined surgical approach and effective reconstructions could improve oncologic and functional prognosis in carefully selected spinal tumor patients.
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http://dx.doi.org/10.1186/s12891-021-04208-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042902PMC
April 2021

Single-Atom Pd Nanozyme for Ferroptosis-Boosted Mild-Temperature Photothermal Therapy.

Angew Chem Int Ed Engl 2021 06 28;60(23):12971-12979. Epub 2021 Apr 28.

State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, P. R. China.

Photothermal therapy (PTT) is an extremely promising tumor therapeutic modality. However, excessive heat inevitably injures normal tissues near tumors, and the damage to cancer cells caused by mild hyperthermia is easily repaired by stress-induced heat shock proteins (HSPs). Thus, maximizing the PTT efficiency and minimizing the damage to healthy tissues simultaneously by adopting appropriate therapeutic temperatures is imperative. Herein, an innovative strategy is reported: ferroptosis-boosted mild PTT based on a single-atom nanozyme (SAzyme). The Pd SAzyme with atom-economical utilization of catalytic centers exhibits peroxidase (POD) and glutathione oxidase (GSHOx) mimicking activities, and photothermal conversion performance, which can result in ferroptosis featuring the up-regulation of lipid peroxides (LPO) and reactive oxygen species (ROS). The accumulation of LPO and ROS provides a powerful approach for cleaving HSPs, which enables Pd SAzyme-mediated mild-temperature PTT.
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http://dx.doi.org/10.1002/anie.202101924DOI Listing
June 2021

Cis-regulation of the amino acid transporter genes ZmAAP2 and ZmLHT1 by ZmPHR1 transcription factors in maize ear under phosphate limitation.

J Exp Bot 2021 05;72(10):3846-3863

The Key Laboratory of Plant-Soil Interactions, MOE, Department of Plant Nutrition, China Agricultural University, Beijing, China.

Phosphorus and nitrogen nutrition have profound and complicated innate connections; however, underlying molecular mechanisms are mostly elusive. PHR1 is a master phosphate signaling component, and whether it directly functions in phosphorus-nitrogen crosstalk remains a particularly interesting question. In maize, nitrogen limitation caused tip kernel abortion and ear shortening. By contrast, moderately low phosphate in the field reduced kernels across the ear, maintained ear elongation and significantly lowered concentrations of total free amino acids and soluble proteins 2 weeks after silking. Transcriptome profiling revealed significant enrichment and overall down-regulation of transport genes in ears under low phosphate. Importantly, 313 out of 847 differentially expressed genes harbored PHR1 binding sequences (P1BS) including those controlling amino acid/polyamine transport and metabolism. Specifically, both ZmAAP2 and ZmLHT1 are plasma membrane-localized broad-spectrum amino acid transporters, and ZmPHR1.1 and ZmPHR1.2 were able to bind to P1BS-containing ZmAAP2 and ZmLHT1 and down-regulate their expression in planta. Taken together, the results suggest that prevalence of P1BS elements enables ZmPHR1s to regulate a large number of low phosphate responsive genes. Further, consistent with reduced accumulation of free amino acids, ZmPHR1s down-regulate ZmAAP2 and ZmLHT1 expression as direct linkers of phosphorus and nitrogen nutrition independent of NIGT1 in maize ear under low phosphate.
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http://dx.doi.org/10.1093/jxb/erab103DOI Listing
May 2021

[Clinical features and genetic analysis of a child with late-onset immune dysregulation, polyendocrinopathy, enteropathy, X-Linked syndrome].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2021 Mar;38(3):255-259

Department of Digestion, Children's Hospital Affiliated to Zhengzhou University, Henan Provinicial Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, Henan 450053, China.

Objective: To report on the clinical features and result of genetic testing for a child featuring immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome.

Methods: Clinical records, genetic testing, laboratory investigation and treatment of the child were summarized in addition with a comprehensive review of the literature.

Results: The 3-year-old boy was administered due to intractable diarrhea, recurrent infections, liver dysfunction and failure to thrive, though no diabetes or skin disorder was observed. Laboratory testing showed elevated liver enzymes and total IgE, decreased albumin and electrolyte imbalance. Gastrointestinal endoscopy revealed erosion and granules in the duodenum, and edema in the terminal ileum and colon. Biopsies showed villous atrophy in the duodenum and terminal ileum. Genetic testing revealed that the patient has carried a missense c.1087A>G (p.I363V) variant in the exon 10 of the FOXP3 gene. He was treated with enteral and parenteral nutrition, anti infection and Sirolimus, and was waiting for hemopoietic stem cell transplantation.

Conclusion: Although IPEX syndrome usually occur during infancy, it should not be ruled out solely based on the age, and its presentation can be variable. For male children with refractory diarrhea, autoimmune disorder and growth retardation, the diagnosis should be suspected and confirmed by genetic testing.
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http://dx.doi.org/10.3760/cma.j.cn511374-20200420-00289DOI Listing
March 2021

Three-wavelength measurement of aerosol absorption using a multi-resonator coupled photoacoustic spectrometer.

Opt Express 2021 Jan;29(2):2258-2269

Aerosol optical absorption measurements are important for the prediction of climate change, as aerosols directly disturb Earth's radiation balance by absorbing or scattering solar radiation. Although photoacoustic spectroscopy is commonly recognized as one of the best candidates to measure the absorption of aerosols, multi-wavelength measurements of aerosols optical absorption remain challenging. Here, a method based on photoacoustic spectroscopy that can simultaneously measure the aerosol absorption characteristics of three wavelengths (404, 637 and 805 nm) is proposed. In the three-wavelength photoacoustic spectrometer (TW-PAS), a photoacoustic cell with three acoustic resonators operating at different resonant frequencies was designed for offering multi-laser (multi-wavelength) operation simultaneously, and only one microphone was used to measure the acoustic signals of all resonators. The performance of TW-PAS was demonstrated and evaluated by measuring and analyzing the wavelength-dependent absorption coefficients of carbonaceous aerosols, which shows good agreement with previously reported results. The developed TW-PAS exhibits high potential for classifying and quantifying different types of light-absorbing aerosols by analyzing its absorption wavelength dependence characteristics.
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http://dx.doi.org/10.1364/OE.412922DOI Listing
January 2021

Case Report: Two Infant Cases of Langerhans Cell Histiocytosis Involving the Digestive Tract.

Front Pediatr 2021 24;9:545771. Epub 2021 Feb 24.

Department of Gastroenterology, The Affiliated Children Hospital of Zhengzhou University, Henan Children Hospital, Zhengzhou, China.

Langerhans cell histiocytosis (LCH) is a rare disease with uncertain etiology. Langerhans cell histiocytosis with involvement of the gastrointestinal tract is rare and is typically identified in pediatric patients with systemic disease. The present study reports two infantile cases of LCH who initially presented with diarrhea, hematochezia, and rash and were histologically missed on the original examination of the colonic biopsy sections. The diagnosis of LCH was later verified through immunohistochemistry. By combining our experience and previous reports, the multiple hemorrhagic spots of the colorectal mucosa and narrowness and erosion of the distal duodenum might be suggestive manifestations of gastrointestinal involvement in LCH on endoscopic examination. This might be helpful for the early recognition of the disease.
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http://dx.doi.org/10.3389/fped.2021.545771DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943473PMC
February 2021

Body Composition Analysis of 10 Years versus 5 Years of Adjuvant Endocrine Therapy in Patients with Nonmetastatic Breast Cancer.

J Oncol 2021 16;2021:6659680. Epub 2021 Jan 16.

Thyroid Breast Surgery Department, Hubei Ezhou Central Hospital, Ezhou, Hubei, China.

Objective: Our study aims to investigate the association of extended adjuvant endocrine therapy with disease-free survival (DFS), muscle mass, muscle strength, and visceral adipose tissue in patients with nonmetastatic breast cancer and the effect of extended endocrine therapy on body composition. . Patients ( = 90) with nonmetastatic breast cancer aged between 60 and 65 years old were prospectively recruited in this study, compromising a cohort of subjects rece iving 5 years or 10 years of adjuvant endocrine therapy. Patients' DFS was compared between these two groups. Patients' body composition including muscle and fat using CT scans, muscle strength, and gait speed was evaluated in these two groups.

Results: Dietary behavior was recorded with the food frequency questionnaire (FFQ). Patients' age, body weight, and body mass index (BMI) did not differ between the two groups. An extended adjuvant endocrine therapy into 10 years could translate into DFS benefit (123.8 vs. 102.2 months, =0.038). Patients receiving 10 years of adjuvant endocrine therapy had less skeletal muscle and more visceral fat compared with patients receiving 5 years of adjuvant endocrine therapy. The skeletal muscle index was 50.3 ± 1.6 cm/m versus 46.5 ± 1.3 cm/m in the 10 years or 5 years of adjuvant endocrine therapy group (=0.042). The visceral fat was 28.9 ± 2.9 cm/m versus 55.0 ± 3.2 cm/m in the 10 years or 5 years of adjuvant endocrine therapy group (=0.011). The muscle strength, gait speed, and FFQ results in the two groups not reaching statistical difference.

Conclusion: In conclusion, breast cancer patients with 10 years of adjuvant endocrine therapy had DFS benefit, but with more muscle loss and adipose tissue deposits compared to patients receiving 5 years of adjuvant endocrine therapy.
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http://dx.doi.org/10.1155/2021/6659680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826243PMC
January 2021

Luminescent net-like inorganic scaffolds with europium-doped hydroxyapatite for enhanced bone reconstruction.

Nanoscale 2021 Jan 6;13(2):1181-1194. Epub 2021 Jan 6.

Department of Periodontology, Stomatological Hospital, Jilin University, Changchun 130021, P. R. China.

Bone reconstruction is an urgent problem during clinical treatment. In the past few decades, the construction of composite scaffolds has been a hot spot in the research field of bone tissue engineering (BTE). However, the disadvantages of composite materials raise our awareness to explore the potential application of hydroxyapatite (HAp) in bone substitutes due to the closest properties of HAp to natural bone tissue. In our study, we synthesized Eu-doped HAp (HAp:Eu) ultralong nanowires, which can be transformed to hydrophilic net-like scaffolds via a thiol-ene click reaction. The property of luminescence of HAp from Eu is beneficial for identifying the relative position of materials and bone marrow mesenchymal stem cells (BMSCs). HAp:Eu scaffolds with excellent cell biocompatibility could promote the expression of early bone formation markers (ALP and ARS) and enhance the expression of genes and proteins associated with osteogenesis (Runx 2, OCN, and OPN). In the end, the results of the in vivo osteogenesis experiment showed that pure HAp scaffolds presented different effects of bone tissue reconstruction compared with the composite scaffolds with HAp nanorods and polymer materials. The superior osteogenic effect could be observed in net-like pure HAp scaffold groups. Furthermore, the absorption of HAp:Eu scaffolds could be monitored due to the luminescence property of Eu. This strategy based on ultralong HAp nanowires proved to be a new method for the construction of simple reticular scaffolds for potential osteogenic applications.
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http://dx.doi.org/10.1039/d0nr05608aDOI Listing
January 2021

Innate lymphoid cells in kidney diseases.

Kidney Int 2021 05 30;99(5):1077-1087. Epub 2020 Dec 30.

Centre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, New South Wales, Australia. Electronic address:

It is well known that innate immune cells, including dendritic cells, macrophages, and natural killer cells, contribute to pathogenesis and protection in various kidney diseases. The understanding of innate immunity has been advanced recently by the discovery of a new group of innate lymphoid cells (ILCs), including ILC1, ILC2, and ILC3. ILCs lack adaptive antigen receptors, yet can be triggered by various pathogens and rapidly provide an abundant source of immunomodulatory cytokines to exert immediate immune reactions and direct subsequent innate and adaptive immune responses. ILCs play critical roles in immunity, tissue homeostasis, and pathological inflammation. In this review, we highlight the biological function of ILC subpopulations in the normal kidney, and their important roles in acute and chronic kidney diseases, thus demonstrating the emerging importance of ILC-regulated immunity in this special organ and providing insights for future research directions and therapeutic interventions.
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http://dx.doi.org/10.1016/j.kint.2020.11.023DOI Listing
May 2021

Development of a 443 nm diode laser-based differential photoacoustic spectrometer for simultaneous measurements of aerosol absorption and NO.

Photoacoustics 2021 Mar 9;21:100229. Epub 2020 Dec 9.

School of Environmental Science and Optoelectronic Technology, University of Science and Technology of China, Hefei 230031, China.

Measurement of ambient aerosol and nitrogen dioxide (NO) is important as they are major pollutants from the burning of fossil fuel and biomass. In the present work, a differential photoacoustic spectrometer (D-PAS) was developed for simultaneous, online measurements of aerosol optical absorption and NO concentration. A novel photoacoustic resonator was designed and employed in the D-PAS for controlling a large flow rate, improving response time, and keeping the flow noise at a low level. The detection limits of 1.0 Mm and 0.87 ppb for aerosol absorption and NO concentration measurements were achieved with a lock-in amplifier time constant of 1 s. The D-PAS accuracy was demonstrated by performing a long-time, continuous measurement of aerosol, and NO in ambient air. The measured results of NO are consistent with the NOx analyzer and environmental monitoring station results.
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http://dx.doi.org/10.1016/j.pacs.2020.100229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749428PMC
March 2021

Persimmon oligomeric proanthocyanidins alleviate ultraviolet B-induced skin damage by regulating oxidative stress and inflammatory responses.

Free Radic Res 2020 Oct 9;54(10):765-776. Epub 2020 Nov 9.

College of Food Science and Technology, Huazhong Agricultural University, Wuhan, China.

Skin damage can be induced by excessive ultraviolet B (UV-B) irradiation. This study aimed to investigate the potential protective activity of persimmon oligo-proanthocyanidins (P-OPC) against UV-B induced human keratinocyte cells (HaCaT cells) and skin damage and its underlying mechanisms and . P-OPC was shown to inhibit the production of intracellular reactive oxygen species (ROS) induced by UVB radiation in both HaCaT cells and mouse skin tissues by increasing the activity of the antioxidant enzyme system [superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione (GSH)]. Furthermore, P-OPC was found to suppress cell apoptosis and the production of inflammatory cytokines, TNF-α, and IL-6. Overall, P-OPC could protect skin tissues from UV-B-induced damage by suppressing oxidant stress, acute inflammation, and cell apoptosis regulating MAPK and NF-κB signalling pathways. These results indicate the potential of P-OPC as a photochemo-protective agent against UV-B induced skin damage.
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http://dx.doi.org/10.1080/10715762.2020.1843651DOI Listing
October 2020

IL-10 producing type 2 innate lymphoid cells prolong islet allograft survival.

EMBO Mol Med 2020 11 9;12(11):e12305. Epub 2020 Oct 9.

Henan Key Laboratory of Immunology and Targeted Drugs, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, China.

Type 2 innate lymphoid cells (ILC2s) are a subset of ILCs with critical roles in immunoregulation. However, the possible role of ILC2s as immunotherapy against allograft rejection remains unclear. Here, we show that IL-33 significantly prolonged islet allograft survival. IL-33-treated mice had elevated numbers of ILC2s and regulatory T cells (Tregs). Depletion of Tregs partially abolished the protective effect of IL-33 on allograft survival, and additional ILC2 depletion in Treg-depleted DEREG mice completely abolished the protective effects of IL-33, indicating that ILC2s play critical roles in IL-33-mediated islet graft protection. Two subsets of ILC2s were identified in islet allografts of IL-33-treated mice: IL-10 producing ILC2s (ILC2 ) and non-IL-10 producing ILC2s (non-ILC ). Intravenous transfer of ILC2 cells, but not non-ILC , prolonged islet allograft survival in an IL-10-dependent manner. Locally transferred ILC2 cells led to long-term islet graft survival, suggesting that ILC2 cells are required within the allograft for maximal suppressive effect and graft protection. This study has uncovered a major protective role of ILC2 in islet transplantation which could be potentiated as a therapeutic strategy.
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http://dx.doi.org/10.15252/emmm.202012305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645373PMC
November 2020

Lipid rafts as potential mechanistic targets underlying the pleiotropic actions of polyphenols.

Crit Rev Food Sci Nutr 2020 Sep 21:1-14. Epub 2020 Sep 21.

College of Food Science and Technology, Huazhong Agricultural University, Wuhan, China.

Polyphenols have attracted a lot of global attention due to their diverse biological actions against cancer, obesity, and cardiovascular diseases. Although extensive research has been carried out to elucidate the mechanisms of pleiotropic actions of polyphenols, this remains unclear. Lipid rafts are distinct nanodomains enriched in cholesterol and sphingolipids, present in the inner and outer leaflets of cell membranes, forming functional platforms for the regulation of cellular processes and diseases. Recent studies focusing on the interaction between polyphenols and cellular lipid rafts shed new light on the pleiotropic actions of polyphenols. Polyphenols are postulated to interact with lipid rafts in two ways: first, they interfere with the structural integrity of lipid rafts, by disrupting their structure and clustering of the ordered domains; second, they modulate the downstream signaling pathways mediated by lipid rafts, by binding to receptor proteins associated with lipid rafts, such as the 67 kDa laminin receptor (67LR), epidermal growth factor receptor (EGFR), and others. This study aims to elaborate the mechanism of interaction between polyphenols and lipid rafts, and describe pleiotropic preventive effects of polyphenols.
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http://dx.doi.org/10.1080/10408398.2020.1815171DOI Listing
September 2020

Platelet membrane-functionalized nanoparticles with improved targeting ability and lower hemorrhagic risk for thrombolysis therapy.

J Control Release 2020 12 25;328:78-86. Epub 2020 Aug 25.

Department of Pharmaceutics, School of Pharmacy, Key Laboratory of Smart Drug Delivery (Ministry of Education and PLA), Fudan University, Shanghai 201203, China; State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai 200032, China; Institute of Integrative Medicine of Fudan University, Shanghai 200041, China; Minhang Branch, Zhongshan Hospital and Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai 201199, China. Electronic address:

Intravenous injection of thrombolytic drugs is the most effective strategy for the treatment of thrombotic diseases. However, the clinical application of most thrombolytic drugs is limited by hemorrhagic risks and narrow therapeutic index. The targeted drug delivery systems may help to address these problems. Inspired by the crucial role of platelets in the process of thrombus, Platelet membrane-coated PLGA cores loading lumbrokinase (PNPs/LBK) were designed for effective thrombolysis with reduced hemorrhagic risk. Using a mouse carotid thrombosis model, the affinity of platelet membrane-coated nanoparticles to the thrombus was confirmed. Also, the PNPs/LBK exhibited excellent thrombolytic efficacy at a low dose, compared with free LBK. More importantly, PNPs/LBK showed less adverse effect on the function of the coagulation system, and thus reduced hemorrhagic risk. These results indicated that a promising thrombus-targeted drug delivery system was achieved by coating PLGA nanoparticles with platelet membrane. Such rationally designed drug delivery system will provide a broad platform for thrombus treatment.
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http://dx.doi.org/10.1016/j.jconrel.2020.08.030DOI Listing
December 2020

The influx/efflux mechanisms of d-peptide ligand of nAChRs across the blood-brain barrier and its therapeutic value in treating glioma.

J Control Release 2020 11 11;327:384-396. Epub 2020 Aug 11.

Minhang Hospital & Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, People's Republic of China. Electronic address:

A d-peptide ligand of the nicotine acetylcholine receptors (nAChRs), termed CDX, enables drug delivery to the brain when incorporated into liposomes and has shown promise as a nanocarrier for treating brain diseases. However, few reports have described the mechanisms whereby CDX-modified liposomes traverse the blood-brain barrier (BBB). Here, we studied the molecular mechanisms enabling CDX (and its associated liposomes) to cross an in vitro BBB using a simulated cerebral endothelium monolayer formed by brain capillary endothelial cells (bEnd.3 cells). We also examined the mechanisms whereby CDX-modified liposomes cross the BBB in vivo using the brain efflux-index method. Transport of CDX and its modified liposomes was dominantly mediated via the lipid raft/caveolae endocytic pathway. Both the endoplasmic reticulum (ER) and Golgi complex participated in delivering CDX-modified liposomes to the plasma membrane (PM). CDX-modified liposomes also participated in the endosome/lysosome pathway (with high-efficiency BBB crossing observed in vitro), while competing for the ER/Golgi/PM pathway. In addition, nAChR α7 did not promote the transportation of CDX-modified liposomes in vivo or in vitro, as assessed with α7-knockout mice and by performing α-bungarotoxin (α-Bgt) binding-competition experiments. P-glycoprotein (P-gp) was identified as the main efflux transporter across the BBB, in vivo and in vitro. Using a xenograft nude mouse model of human glioblastoma multiforme, blocking the efflux function of P-gp with verapamil enhanced the therapeutic efficiency of CDX-modified liposomes that were formulated with doxorubicin against glioblastoma. The findings of this study reveal novel mechanisms underlying crossing of the BBB by CDX-modified liposomes, suggesting that CDX-modified liposomes can potentially serve as a powerful therapeutic tool for treating glioma.
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http://dx.doi.org/10.1016/j.jconrel.2020.08.010DOI Listing
November 2020

Discovery of 7H-pyrrolo[2,3-d]pyridine derivatives as potent FAK inhibitors: Design, synthesis, biological evaluation and molecular docking study.

Bioorg Chem 2020 09 14;102:104092. Epub 2020 Jul 14.

Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.

Focal adhesion kinase (FAK) is an intracellular non-receptor tyrosine kinase responsible for development of various tumor types. Aiming to explore new potent inhibitors, two series of 2,4-disubstituted-7H-pyrrolo[2,3-d]pyrimidine derivatives were designed and synthesized on the base of structure-based design strategy. Biological evaluation indicated that most of these new compounds could potently inhibit FAK kinase, leading to the promising inhibitors against the proliferation of U-87MG, A-549, and MDA-MB-231 cancer cell lines. Among them, the optimized compound 18h potently inhibited the enzyme (IC = 19.1 nM) and displayed stronger potency than TAE-226 in U-87MG, A-549 and MDA-MB-231 cells, with IC values of 0.35, 0.24, and 0.34 μM, respectively. Compound 18h is a multi-target kinase inhibitor. Furthermore, compound 18h also exhibited relatively less cytotoxicity (IC = 3.72 μM) toward a normal human cell line, HK2. According to the flow cytometry and wound healing assay results, compound 18h effectively induced apoptosis and G0/G1 phase arrest of MDA-MB-231 cells and suppressed the migration of U-87MG, A-549 and MDA-MB-231 cells. The docking study of compound 18h was performed to elucidate its possible binding modes and to provide a structural basis for the further structural guidance design of FAK inhibitors. Collectively, these data support the further development of compound 18h as a lead compound for FAK-targeted anticancer drug discovery.
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http://dx.doi.org/10.1016/j.bioorg.2020.104092DOI Listing
September 2020

Discovery of 2,4-diaminopyrimidine derivatives targeting p21-activated kinase 4: Biological evaluation and docking studies.

Arch Pharm (Weinheim) 2020 Oct 6;353(10):e2000097. Epub 2020 Jul 6.

Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang, China.

In this study, novel 2,4-diaminopyrimidine derivatives targeting p21-activated kinase 4 (PAK4) were discovered and evaluated for their biological activity against PAK4. Among the derivatives studied, promising compounds A2, B6, and B8 displayed the highest inhibitory activities against PAK4 (IC  = 18.4, 5.9, and 20.4 nM, respectively). From the cellular assay, compound B6 exhibited the highest potency with an IC value of 2.533 μM against A549 cells. Some compounds were selected for computational ADME (absorption, distribution, metabolism, and elimination) properties and molecular docking studies against PAK4. The detailed structure-activity relationship based on the biochemical activities and molecular docking studies were explored. According to the docking studies, compound B6 had the lowest docking score (docking energy: -7.593 kcal/mol). The molecular docking simulation indicated the binding mode between compound B6 and PAK4. All these results suggest compound B6 as a useful candidate for the development of a PAK4 inhibitor.
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http://dx.doi.org/10.1002/ardp.202000097DOI Listing
October 2020

A development strategy to fast establish the Taqman qPCR based method to detect SNP mutations.

Hum Cell 2020 Oct 1;33(4):1331-1333. Epub 2020 Jul 1.

Chengdu Neo-Life Hope Medical Lab. Co. Ltd, Chengdu, 610036, Sichuan, People's Republic of China.

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http://dx.doi.org/10.1007/s13577-020-00390-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7327208PMC
October 2020

Encodes a Distinct Type of Carotenoid Cleavage Dioxygenase and Enhances Plant Tolerance to Low Phosphate.

Plant Physiol 2020 09 25;184(1):374-392. Epub 2020 Jun 25.

Department of Plant Nutrition, College of Resources and Environmental Sciences, China Agricultural University, MOE, Beijing 100193, China

Carotenoid cleavage dioxygenases (CCDs) drive carotenoid catabolism to produce various apocarotenoids and immediate derivatives with particular developmental, ecological, and agricultural importance. How genes evolved with species diversification and the resulting functional novelties in cereal crops have remained largely elusive. We constructed a unified four-clade phylogenetic tree of s, revealing a previously unanchored basal clade underwent highly dynamic duplication or loss events, even in the grass family. Different from cleavage sites of CCD8 and ZAXINONE SYNTHASE (ZAS), maize () ZmCCD10a cleaved differentially structured carotenoids at 5, 6 (5', 6') and 9, 10 (9', 10') positions, generating C (6-methyl-5-hepten-2-one) and C (geranylacetone, α-ionone, and β-ionone) apocarotenoids in Localized in plastids, ZmCCD10a cleaved neoxanthin, violaxanthin, antheraxathin, lutein, zeaxanthin, and β-carotene in planta, corroborating functional divergence of ZmCCD10a and ZAS. expression was dramatically stimulated in maize and teosinte ( ssp. , ssp. , , and ) roots by phosphate (Pi) limitation. silencing favored phosphorus retention in the root and reduced phosphorus and biomass accumulation in the shoot under low Pi. Overexpression of in Arabidopsis () enhanced plant tolerance to Pi limitation by preferential phosphorus allocation to the shoot. Thus, encodes a unique CCD facilitating plant tolerance to Pi limitation. Additionally, silencing and overexpression led to coherent alterations in expression of () and Pi transporters, and cis-regulation of expression by ZmPHR1;1 and ZmPHR1;2 implies a probable -involved regulatory pathway that adjusts Pi allocation.
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http://dx.doi.org/10.1104/pp.20.00378DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7479897PMC
September 2020

Guanidyl and imidazolyl integration group-modified PAMAM for gastric adenocarcinoma gene therapy.

J Gene Med 2020 10 17;22(10):e3240. Epub 2020 Jul 17.

Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, Shanghai, China.

Background: Gene therapy has become a potential strategy for cancer treatment. However, the development of efficient gene vectors restricts the application for cancer gene treatment. Functionalization of polymers with functional groups can significantly improve their transfection efficacy.

Methods: Guanidyl can form bidentate hydrogen with the phosphate groups and phosphate groups are present in DNA and cell membranes, thus increasing DNA condensation and cellular uptake. Imidazolyl has high buffering capacity in endosomal/lysosomal acidic environment, facilitating endosome/lysosome escape. We designed a structure-integrated group of guanidyl and imidazolyl, 2-aminoimidazole (AM), which was conjugated to PAMAM generation 2 (G2) for gene therapy of gastric adenocarcinoma.

Results: Molecular docking results illustrated that G2-AM bound with DNA molecule effectively via multiple interactions. A quantitative luciferase assay showed that the transfection efficacy of G2-AM/pGL3 was approximately 100-fold greater than that of G2/pGL3, 90-fold greater than that of imidazolyl-modified G2 (G2-M) /pGL3 and 100-fold greater than that of G5/pGL3 without additional cytotoxicity. After introducing the pTRAIL gene into gastric adenocarcinoma cells, the apoptosis ratio of gastric adenocarcinoma cells treated with G2-AM/pTRAIL was 36.95%, which is much larger than the corresponding ratio of G2/pTRAIL (7.45%), G2-M/pTRAIL (11.33%) and G5/pTRAIL (23.2%). In a gastric adenocarcinoma xenograft model, the in vivo transfection efficacy of G2-AM/pRFP was much greater than that of G2/pRFP and G2-M/pRFP.

Conclusions: These results demonstrate that AM could be modified with cationic polymers for potential application in gene delivery and gastric adenocarcinoma gene therapy.
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http://dx.doi.org/10.1002/jgm.3240DOI Listing
October 2020

The protective effects of the β3 adrenergic receptor agonist BRL37344 against liver steatosis and inflammation in a rat model of high-fat diet-induced nonalcoholic fatty liver disease (NAFLD).

Mol Med 2020 06 5;26(1):54. Epub 2020 Jun 5.

Gastroenterology Department, the First Affiliated Hospital of Harbin Medical University, #23 Postal Street, Harbin, 150001, Heilongjiang, China.

Background: Our objective was to investigate the efficacy of the beta-3 adrenergic receptor (β3-AR) agonist BRL37344 for the prevention of liver steatosis and inflammation associated with nonalcoholic fatty liver disease (NAFLD).

Methods: Four groups were established: a control group (given a standard diet), a high-fat diet (HFD) group, an HFD + β3-AR agonist (β3-AGO) group, and an HFD + β3-AR antagonist (β3-ANT) group. All rats were fed for 12 weeks. The β3-AR agonist BRL37344 and the antagonist L748337 were administered for the last 4 weeks with Alzet micro-osmotic pumps. The rat body weights (g) were measured at the end of the 4th, 8th, and 12th weeks. At the end of the 12th week, the liver weights were measured. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed with a Hitachi automatic analyzer. The lipid levels of the triglycerides (TGs), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) and the concentrations of free fatty acids (FFAs) were also measured. An oil red O kit was used to detect lipid droplet accumulation in hepatocytes. Steatosis, ballooning degeneration and inflammation were histopathologically determined. The protein and mRNA expression levels of β3-AR, peroxisome proliferator-activated receptor-alpha (PPAR-α), peroxisome proliferator-activated receptor-gamma (PPAR-γ), mitochondrial carnitine palmitoyltransferase-1 (mCPT-1), and fatty acid translocase (FAT)/CD36 were measured by western blot analysis and RT-qPCR, respectively.

Results: After treatment with the β3-AR agonist BRL37344 for 4 weeks, the levels of ALT, AST, TGs, TC, LDL-C and FFAs were decreased in the NAFLD model group compared with the HFD group. Body and liver weights, liver index values and lipid droplet accumulation were lower in the HFD + β3-AGO group than in the HFD group. Decreased NAFLD activity scores (NASs) also showed that liver steatosis and inflammation were ameliorated after treatment with BRL37344. Moreover, the β3-AR antagonist L748337 reversed these effects. Additionally, the protein and gene expression levels of β3-AR, PPAR-α, and mCPT-1 were increased in the HFD + β3-AGO group, whereas those of PPAR-γ and FAT/CD36 were decreased.

Conclusion: The β3-AR agonist BRL37344 is beneficial for reducing liver fat accumulation and for ameliorating liver steatosis and inflammation in NAFLD. These effects may be associated with PPARs/mCPT-1 and FAT/CD36.
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http://dx.doi.org/10.1186/s10020-020-00164-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275314PMC
June 2020

Persimmon highly galloylated-tannins in vitro mitigated α-amylase and α-glucosidase via statically binding with their catalytic-closed sides and altering their secondary structure elements.

J Food Biochem 2020 07 17;44(7):e13234. Epub 2020 Apr 17.

College of Food Science and Technology, Huazhong Agricultural University, Wuhan, China.

Reticence of α-amylase (α-Amy) and α-glucosidase (α-Glu) is needed due to their mitigation potency on the glucose absorption. In this study, the anti-amylolytic effects of persimmon tannins (PT) on α-Amy and α-Glu and their interaction mechanisms were investigated. It was found that PT inhibited α-Amy and α-Glu with the half inhibitory concentration (IC ) values of 0.35 and 0.24 mg/ml, respectively. Fluorescence and FT-IR spectrometry results showed that PT could bind to enzymes and alter their conformations. Molecular docking showed that the structural units of PT interacted with the key sites (amino acids Glu233, Asp197, and Asp300) of α-Amy by H-bonds and π-π interactions, while they bound to the residues closed to the active sites of α-Glu. The whole results implied that PT was a promising mitigator of α-Amy and α-Glu. It might help to understand mechanisms of glycemic response inhibition of PT and develop certain therapeutic strategies against diabetes. PRACTICAL APPLICATIONS: α-Amy and α-Glu are the crucial starch digestive enzymes associated with type II diabetes mellitus in humans. Persimmon is an excellent source of bio-functional tannins which potentially mitigate the type II diabetes. This study showed that PT beneficially decreased the action of the carbohydrate digestion-related enzymes, namely α-Amy and α-Glu via interaction simultaneously, which could be used to formulate a functional food and natural medicine.
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http://dx.doi.org/10.1111/jfbc.13234DOI Listing
July 2020

Is fractal dimension a reliable imaging biomarker for the quantitative classification of an intervertebral disk?

Eur Spine J 2020 05 17;29(5):1175-1180. Epub 2020 Mar 17.

Department of Radiology, The Affiliated Hospital of Shaanxi University of Chinese Medicine, 2# Weiyang Western Road, Xianyang, 712000, China.

Purpose: This study aimed to explore the feasibility of the fractal method used in decoding disk heterogeneity, hoping to find a reliable imaging biomarker for the quantitative and continuous grading of intervertebral disks (IVDs).

Methods: Totally, 180 IVDs in 65 low back pain patients (29 males, 36 female, 28-69 years) were examined with MRI. Each IVD was manually segmented on axial slice (at the mid-height layer of the disk). All disks were visually evaluated regarding degeneration grade, using Pfirrmann classification, by two experienced radiologists. Fractal dimension (FD) of the IVD was calculated from the defined regions of interest and correlated with Pfirrmann grade.

Results: Fractal dimension differed significantly between any two groups (P < 0.01). The mean FDs for the four grades were as follows: Pfirrmann 1: 1.13 ± 0.02; Pfirrmann 2: 1.30 ± 0.05; Pfirrmann 3: 1.50 ± 0.05; and Pfirrmann 4: 1.65 ± 0.02. The well-hydrated IVDs displayed low fractal dimension. Degenerated IVDs displayed increased fractal dimension caused by disk heterogeneity, where the fractal dimension was shown to correlate strongly with Pfirrmann grade.

Conclusions: Fractal dimension associated well with IVD degeneration, determined with Pfirrmann grading, suggesting that the IVD fractal analysis was a suitable detection tool for the objective and continuous classification of IVD degeneration. These slides can be retrieved under Electronic Supplementary Material.
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http://dx.doi.org/10.1007/s00586-020-06370-2DOI Listing
May 2020