Publications by authors named "Jinming Zhang"

260 Publications

Towards a better understanding of Fagopyrum dibotrys: a systematic review.

Chin Med 2021 Sep 16;16(1):89. Epub 2021 Sep 16.

Key Laboratory of Coarse Cereal Processing of Ministry of Agriculture and Rural Affairs, Chengdu University, Chengdu, China.

Fagopyrum dibotrys (F. dibotrys) (D.Don) H.Hara is a well-known edible herbal medicine in Asian countries. It has been widely used for the treatment of lung diseases, swelling, etc., and is also an important part of many Chinese medicine prescriptions. At present, more than 100 compounds have been isolated and identified from F. dibotrys, and these compounds can be primarily divided into flavonoids, phenols, terpenes, steroids, and fatty acids. Flavonoids and phenolic compounds are considered to be the main active ingredients of F. dibotrys. Previous pharmacological studies have shown that F. dibotrys possesses anti-inflammatory, anti-cancer, anti-oxidant, anti-bacterial, and anti-diabetic activities. Additional studies on functional genes have led to a better understanding of the metabolic pathways and regulatory factors related with the flavonoid active ingredients in F. dibotrys. In this paper, we systemically reviewed the research advances on the phytochemistry and pharmacology of F. dibotrys, as well as the functional genes related to the synthesis of active ingredients, aiming to promote the development and utilization of F. dibotrys.
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http://dx.doi.org/10.1186/s13020-021-00498-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447528PMC
September 2021

MD2 contributes to the pathogenesis of perioperative neurocognitive disorder via the regulation of α5GABA receptors in aged mice.

J Neuroinflammation 2021 Sep 16;18(1):204. Epub 2021 Sep 16.

Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, Air Force Medical University, Xi'an, 710032, China.

Background: Perioperative neurocognitive disorder (PND) is a long-term postoperative complication in elderly surgical patients. The underlying mechanism of PND is unclear, and no effective therapies are currently available. It is believed that neuroinflammation plays an important role in triggering PND. The secreted glycoprotein myeloid differentiation factor 2 (MD2) functions as an activator of the Toll-like receptor 4 (TLR4) inflammatory pathway, and α5GABA receptors (α5GABARs) are known to play a key role in regulating inflammation-induced cognitive deficits. Thus, in this study, we aimed to investigate the role of MD2 in PND and determine whether α5GABARs are involved in the function of MD2.

Methods: Eighteen-month-old C57BL/6J mice were subjected to laparotomy under isoflurane anesthesia to induce PND. The Barnes maze was used to assess spatial reference learning and memory, and the expression of hippocampal MD2 was assayed by western blotting. MD2 expression was downregulated by bilateral injection of AAV-shMD2 into the hippocampus or tail vein injection of the synthetic MD2 degrading peptide Tat-CIRP-CMA (TCM) to evaluate the effect of MD2. Primary cultured neurons from brain tissue block containing cortices and hippocampus were treated with Tat-CIRP-CMA to investigate whether downregulating MD2 expression affected the expression of α5GABARs. Electrophysiology was employed to measure tonic currents. For α5GABARs intervention experiments, L-655,708 and L-838,417 were used to inhibit or activate α5GABARs, respectively.

Results: Surgery under inhaled isoflurane anesthesia induced cognitive impairments and elevated the expression of MD2 in the hippocampus. Downregulation of MD2 expression by AAV-shMD2 or Tat-CIRP-CMA improved the spatial reference learning and memory in animals subjected to anesthesia and surgery. Furthermore, Tat-CIRP-CMA treatment decreased the expression of membrane α5GABARs and tonic currents in CA1 pyramidal neurons in the hippocampus. Inhibition of α5GABARs by L-655,708 alleviated cognitive impairments after anesthesia and surgery. More importantly, activation of α5GABARs by L-838,417 abrogated the protective effects of Tat-CIRP-CMA against anesthesia and surgery-induced spatial reference learning and memory deficits.

Conclusions: MD2 contributes to the occurrence of PND by regulating α5GABARs in aged mice, and Tat-CIRP-CMA is a promising neuroprotectant against PND.
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http://dx.doi.org/10.1186/s12974-021-02246-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8444589PMC
September 2021

Lentinan-Based Oral Nanoparticle Loaded Budesonide With Macrophage-Targeting Ability for Treatment of Ulcerative Colitis.

Front Bioeng Biotechnol 2021 27;9:702173. Epub 2021 Aug 27.

State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Ulcerative colitis (UC) is a global, chronic, and refractory disease. Corticosteroids are first-line drugs for the treatment of UC but also cause adverse side effects. Budesonide (BUD), a corticosteroid with relatively low side effects, has been approved by the Food and Drug Administration for use as enteric capsules (Entocort EC) for the treatment of inflammatory bowel disease (IBD). However, this formulation lacks specific targeting ability to UC lesions. Herein, we describe the development of an advanced macrophage-targeted oral lentinan (LNT)-based nanoparticles (NPs) loaded BUD for treatment of UC. Briefly, LNT was used as a food source and natural carrier to load BUD by a simple solvent evaporation method to form LNT/BUD-NPs. LNT showed good loading capacity with high encapsulation and loading efficiencies to BUD of approximately 92.19 and 9.58%, respectively. Evaluation of the gastric stability of LNT/BUD-NPs indicated that LNT could effectively protect BUD from gastric acid and digestive enzymes. The release behavior and transmission electron microscopy image of LNT/BUD-NPs in the intestinal content of mice confirmed that intestinal flora can promote BUD release from LNT. Moreover, evaluation of cellular uptake showed that LNT/BUD-NPs could specifically target macrophages and enhance their uptake rate the Dectin-1 receptor. In biodistribution studies, LNT/BUD-NPs were able to efficiently accumulate in the inflamed colon of mice. As expected, LNT/BUD-NPs could significantly alleviate inflammation by inhibiting the TLR4/MyD88/NF-κB signaling pathway. Therefore, LNT/BUD-NPs have the advantages of good gastric stability, release mediated by mouse intestinal content, macrophage-targeting, and anti-UC effects. These advantages indicate LNT-based NPs are a promising oral drug delivery system for UC therapy.
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http://dx.doi.org/10.3389/fbioe.2021.702173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429481PMC
August 2021

Traditional herbal medicine and nanomedicine: Converging disciplines to improve therapeutic efficacy and human health.

Adv Drug Deliv Rev 2021 Sep 6;178:113964. Epub 2021 Sep 6.

Jiangsu Engineering Research Center for Efficient Delivery System of TCM, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu, China. Electronic address:

Traditional herbal medicine (THM), an ancient science, is a gift from nature. For thousands of years, it has helped humans fight diseases and protect life, health, and reproduction. Nanomedicine, a newer discipline has evolved from exploitation of the unique nanoscale morphology and is widely used in diagnosis, imaging, drug delivery, and other biomedical fields. Although THM and nanomedicine differ greatly in time span and discipline dimensions, they are closely related and are even evolving toward integration and convergence. This review begins with the history and latest research progress of THM and nanomedicine, expounding their respective developmental trajectory. It then discusses the overlapping connectivity and relevance of the two fields, including nanoaggregates generated in herbal medicine decoctions, the application of nanotechnology in the delivery and treatment of natural active ingredients, and the influence of physiological regulatory capability of THM on the in vivo fate of nanoparticles. Finally, future development trends, challenges, and research directions are discussed.
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http://dx.doi.org/10.1016/j.addr.2021.113964DOI Listing
September 2021

Extracellular HSP90α Interacts With ER Stress to Promote Fibroblasts Activation Through PI3K/AKT Pathway in Pulmonary Fibrosis.

Front Pharmacol 2021 23;12:708462. Epub 2021 Aug 23.

Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Pulmonary fibrosis is characterized by alveolar epithelial cell injury, lung fibroblast proliferation, differentiation, and extracellular matrix (ECM) deposition. Our previous study indicated that extracellular HSP90α (eHSP90α) promotes pulmonary fibrosis by activating the MAPK signaling pathway. Thus, treatment with 1G6-D7 (a selective HSP90α monoclonal antibody) to antagonize eHSP90α could effectively ameliorate fibrosis. This study aimed to elucidate the mechanism underlying the effects of eHSP90α in pulmonary fibrosis by focusing on its link with endoplasmic reticulum (ER) stress. Our results showed that eHSP90α promoted lung fibroblast differentiation by activating ER stress. Treatment with the ER stress inhibitor tauroursodeoxycholate (TUDCA) or glucose-regulated protein 78 kDa (GRP78) depletion significantly abrogated the effect of eHSP90α on ER stress and fibroblast activation. In addition, eHSP90α induced ER stress in fibroblasts the phosphoinositide-4,5-bisphosphate 3-kinase (PI3K)-protein kinase B (AKT) signaling pathway, which could be blocked by the PI3K/AKT inhibitor LY294002, and blockade of eHSP90α by 1G6-D7 markedly inhibited ER stress in the model, indicating preventive and therapeutic applications. Intriguingly, we observed that TUDCA effectively reduced the secretion of eHSP90α and . In conclusion, this study shows that the interaction between eHSP90α and ER stress plays a crucial role in pulmonary fibrosis, indicating a positive feedback in lung fibroblasts. Targeting eHSP90α and alleviating fibroblast ER stress may be promising therapeutic approaches for pulmonary fibrosis.
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http://dx.doi.org/10.3389/fphar.2021.708462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8420756PMC
August 2021

Ga-labeled ODAP-Urea-based PSMA agents in prostate cancer: first-in-human imaging of an optimized agent.

Eur J Nucl Med Mol Imaging 2021 Aug 28. Epub 2021 Aug 28.

Department of Nuclear Medicine, Peking University First Hospital, Beijing, 100034, China.

Purpose: Prostate-specific membrane antigen (PSMA) is a promising target for prostate cancer imaging and therapy. The most commonly used scaffold incorporates a glutamate-urea (Glu-Urea) function. We recently developed oxalyldiaminopropionic acid-urea (ODAP-Urea) PSMA ligands in an attempt to improve upon the pharmacokinetic properties of existing agents. Here, we report the synthesis of an optimized Ga-labeled ODAP-Urea-based ligand, [Ga]Ga-P137, and first-in-human results.

Methods: Twelve ODAP-Urea-based ligands were synthesized and radiolabeled with Ga in high radiochemical yield and purity. Their PSMA inhibitory capacities were determined using the NAALADase assay. Radioligands were evaluated in mice-bearing 22Rv1 prostate tumors by microPET. Lead compound [Ga]Ga-P137 was evaluated for stability, cell uptake, and biodistribution. PET imaging of [Ga]Ga-P137 was performed in three patients head-to-head compared to [Ga]Ga-PSMA-617.

Results: Ligands were synthesized in 11.1-44.4% yield and > 95% purity. They have high affinity to PSMA (K of 0.13 to 5.47 nM). [Ga]Ga-P137 was stable and hydrophilic. [Ga]Ga-P137 showed higher uptake than [Ga]Ga-PSMA-617 in tumor-bearing mice at 6.43 ± 0.98%IA/g vs 3.41 ± 1.31%IA/g at 60-min post-injection. In human studies, the normal organ biodistribution of [Ga]Ga-P137 was grossly equivalent to that of [Ga]Ga-PSMA-617 except for within the urinary tract, in which [Ga]Ga-P137 demonstrated lower uptake.

Conclusion: The optimized ODAP-Urea-based ligand [Ga]Ga-P137 can image PSMA in xenograft models and humans, with lower bladder accumulation to the Glu-Urea-based agent, [Ga]Ga-PSMA-617, in a preliminary, first-in-human study.

Trial Registration: ClinicalTrials.gov Identifier: NCT04560725, Registered 23 September 2020. https://clinicaltrials.gov/ct2/show/NCT04560725.
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http://dx.doi.org/10.1007/s00259-021-05486-xDOI Listing
August 2021

Electrochemical process of early-stage corrosion detection based on N-doped carbon dots with superior Fe responsiveness.

J Colloid Interface Sci 2021 Aug 12;606(Pt 1):567-576. Epub 2021 Aug 12.

Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, PR China.

Iron corrosion is a subject of great technological importance and extensive public concern. However, the highly efficient detection of iron corrosion at early stage is still a challenging task. Herein, bright fluorescent carbon dots (CDs) with superior response to Fe were prepared by simple solvothermal process based on citric acid and ammonia. The obtained CDs are able to rapidly, sensitively and selectively respond to Fe. The quantitative analysis showed that the CDs exhibited a linear response to Fe in the range of 10 to 300 µM, with a detection limit of 0.9 μM. And the fluorescence quenching of CDs was obvious enough to be detected by the naked eyes. Such promising responsiveness of CDs offers a great opportunity for real-time and visual detection of Fe during electrochemical corrosion process. In addition, due to the excellent stability and solubility of CDs, patterned papers and hydrogels have been fabricated utilizing cellulose and PVA as matrices. The as-prepared biocompatible, environmental-friendly and disposable CDs based fluorescent materials were successfully used for detecting the degree of iron corrosion. This could provide a simple and visual strategy for monitoring the safety of structural metal materials.
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http://dx.doi.org/10.1016/j.jcis.2021.08.058DOI Listing
August 2021

Stereotactic technology for 3D bioprinting: from the perspective of robot mechanism.

Biofabrication 2021 Aug 13;13(4). Epub 2021 Aug 13.

Key Laboratory for Biomechanics and Mechanobiology of Chinese Education Ministry, Beijing Advanced Innovation Centre for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, People's Republic of China.

Three-dimensional (3D) bioprinting has been widely applied in the field of biomedical engineering because of its rapidly individualized fabrication and precisely geometric designability. The emerging demand for bioprinted tissues/organs with bio-inspired anisotropic property is stimulating new bioprinting strategies. Stereotactic bioprinting is regarded as a preferable strategy for this purpose, which can perform bioprinting at the target position from any desired orientation in 3D space. In this work, based on the motion characteristics analysis of the stacked bioprinting technologies, mechanism configurations and path planning methods for robotic stereotactic bioprinting were investigated and a prototype system based on the double parallelogram mechanism was introduced in detail. Moreover, the influence of the time dimension on stereotactic bioprinting was discussed. Finally, technical challenges and future trends of stereotactic bioprinting within the field of biomedical engineering were summarized.
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http://dx.doi.org/10.1088/1758-5090/ac1846DOI Listing
August 2021

Oral delivery of natural active small molecules by polymeric nanoparticles for the treatment of inflammatory bowel diseases.

Adv Drug Deliv Rev 2021 Sep 24;176:113887. Epub 2021 Jul 24.

State Key Laboratory of Silkworm Genome Biology, College of Sericulture, Textile, and Biomass Sciences, Southwest University, Beibei, Chongqing 400715, China. Electronic address:

The incidence of inflammatory bowel disease (IBD) is rapidly rising throughout the world. Although tremendous efforts have been made, limited therapeutics are available for IBD management. Natural active small molecules (NASMs), which are a gift of nature to humanity, have been widely used in the prevention and alleviation of IBD; they have numerous advantageous features, including excellent biocompatibility, pharmacological activity, and mass production potential. Oral route is the most common and acceptable approach for drug administration, but the clinical application of NASMs in IBD treatment via oral route has been seriously restricted by their inherent limitations such as high hydrophobicity, instability, and poor bioavailability. With the development of nanotechnology, polymeric nanoparticles (NPs) have provided a promising platform that can efficiently encapsulate versatile NASMs, overcome multiple drug delivery barriers, and orally deliver the loaded NASMs to targeted tissues or cells while enhancing their stability and bioavailability. Thus, NPs can enhance the preventive and therapeutic effects of NASMs against IBD. Herein, we summarize the recent knowledge about polymeric matrix-based carriers, targeting ligands for drug delivery, and NASMs. We also discuss the current challenges and future developmental directions.
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http://dx.doi.org/10.1016/j.addr.2021.113887DOI Listing
September 2021

Synthesis of casein-γ-polyglutamic acid hydrogels by microbial transglutaminase-mediated gelation for controlled release of drugs.

J Biomater Appl 2021 Aug;36(2):237-245

College of Bioengineering, Henan University of Technology, Zhengzhou, Henan, China.

Casein-based hydrogels were reported as biodegradability, biocompatibility, and non-toxic materials that had potential in drug delivery. At present, we prepared two kinds of casein/γ-PGA hybrid hydrogels, 1/5 and 1/9, based on the ratio of γ-PGA to casein. The hydrogels were crosslinked by microbial transglutaminase (MTG), the physicochemical properties of the casein/γ-PGA hydrogels were investigated by scanning electron microscopy (SEM) observation, differential scanning calorimetry (DSC) analysis, texture analysis, swelling ratio test, and stability test. The hydrogels showed a well-interconnected sparse and porous structure. The 1/5 casein/γ-PGA hydrogel was much stable, hard, and cohesive than the 1/9 casein/γ-PGA hydrogel, and the 1/5 casein/γ-PGA hydrogel showed a higher swelling ratio and lower degradation rate. To investigate release behavior, we chose the hydrophilic vitamin B12 and hydrophobic aspirin as the model drugs incorporated into the casein/γ-PGA hydrogels. The 1/5 casein/γ-PGA hydrogel exhibited a good drug release behavior.
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http://dx.doi.org/10.1177/08853282211011724DOI Listing
August 2021

Oral Core-Shell Nanoparticles Embedded in Hydrogel Microspheres for the Efficient Site-Specific Delivery of Magnolol and Enhanced Antiulcerative Colitis Therapy.

ACS Appl Mater Interfaces 2021 Jul 15;13(29):33948-33961. Epub 2021 Jul 15.

State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611130, China.

Although magnolol (Mag), an anti-inflammatory natural compound, has been demonstrated to play protective effects on ulcerative colitis (UC), its application as an alternative therapeutic reagent for UC treatment is still greatly impeded due to its poor stability in the gastrointestinal tract and insufficient accumulation in the inflamed colon lesion. Nano-/microsized drug delivery systems can potentially overcome some challenges regarding the oral administration of phytochemicals, which still confront premature early drug release, degradation of NPs, or the sustained drug release of MPs. In this study, we primarily loaded Mag into the core-shell zein-based nanoparticles with chondroitin sulfate coating ([email protected] NPs) with an average size of 142.27 ± 5.11 nm, showing significant macrophage-targeting and enhanced colon epithelial cellular uptake capacity. Then, we embedded [email protected] NPs into hydrogel microspheres via an electrospraying technology. The [email protected] NPsinMPs presented a uniform-sized sphere with an average size of 164.36 ± 6.29 μm and sustained drug-release profiles. Compared to CS-Zein NPs, the developed CS-Zein NPsinMPs exhibited prolonged colon retention on the inflammatory surface, as seen from and imaging fluorescence adhesion experiments. Based on the advantage of the combination of hybrid nanoparticles-in-microparticles, oral administration of [email protected] NPsinMPs significantly alleviated colitis symptoms in DSS-treated mice by regulating the expression levels of proinflammatory cytokines (TNF-α, IL-6, and IL-1β) and anti-inflammatory cytokines (IL-10) and factor accelerated colonic mucosal barrier repair via upregulating the expression of ZO-1 and occludin. This study provides great insights into the oral drug delivery of natural compounds for UC therapy.
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http://dx.doi.org/10.1021/acsami.1c09804DOI Listing
July 2021

Geochemical Baseline Establishment and Source-Oriented Ecological Risk Assessment of Heavy Metals in Lime Concretion Black Soil from a Typical Agricultural Area.

Int J Environ Res Public Health 2021 06 26;18(13). Epub 2021 Jun 26.

School of Ecology and Environment, Anhui Normal University, Wuhu 241000, China.

To accurately assess the potential ecological risk posed by heavy metals in lime concretion black soil and quantify the risk contributions from different sources, an investigation of 217 surface soil samples and 56 subsoil samples was performed in the southern part of Suzhou City. Geochemical baseline values of soil heavy metals (Cr, Zn, Pb, Ni, Hg, Cu, Cd, As, Mn and Co) in the study area were calculated as 53.6, 61.5, 19.8, 27.6, 0.08, 18.4, 0.13, 12.9, 416.1 and 11.0 mg/kg, respectively, by using reference metal normalization and cumulative frequency curve methods. Subsequently, four potential sources of soil heavy metals were identified by the positive matrix factorization. Finally, the potential ecological risks arising from the identified sources were determined by the integrated model of positive matrix factorization and Hakanson potential ecological risk index. Results showed that the ecological risk posed by soil heavy metals in the study area ranged from low to moderate level. Hg and Cd were the two largest risk contributors, supplying 36.0% and 30.3% of total risk value. The origin of heavy metals in the soils is mostly related to four sources including agricultural activities, natural dispersion, coal consumption and traffic pollution. Source apportionment of the potential ecological risks revealed that the dominant risk source in the study area was natural dispersion (42.0%), followed by coal related industries (26.5%), agricultural activities (20.4%) and traffic pollution (11.1%). This work gives a clear baseline information of the heavy metal accumulations in lime concretion black soil and provides a successful case study for the source-oriented ecological risk assessment.
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http://dx.doi.org/10.3390/ijerph18136859DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8297080PMC
June 2021

Novel CD44-targeting and pH/redox-dual-stimuli-responsive core-shell nanoparticles loading triptolide combats breast cancer growth and lung metastasis.

J Nanobiotechnology 2021 Jun 23;19(1):188. Epub 2021 Jun 23.

State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, College of Pharmacy, Chengdu University of Traditional Chinese Medicine, No. 1166 Liutai Avenue, Wenjiang District, Chengdu, China.

Background: The toxicity and inefficient delivery of triptolide (TPL) in tumor therapy have greatly limited the clinical application. Thus, we fabricated a CD44-targeting and tumor microenvironment pH/redox-sensitive nanosystem composed of hyaluronic acid-vitamin E succinate and poly (β-amino esters) (PBAEss) polymers to enhance the TPL-mediated suppression of breast cancer proliferation and lung metastasis.

Results: The generated TPL nanoparticles (NPs) had high drug loading efficiency (94.93% ± 2.1%) and a desirable average size (191 nm). Mediated by the PBAEss core, TPL/NPs displayed a pH/redox-dual-stimuli-responsive drug release profile in vitro. Based on the hyaluronic acid coating, TPL/NPs exhibited selective tumor cellular uptake and high tumor tissue accumulation capacity by targeting CD44. Consequently, TPL/NPs induced higher suppression of cell proliferation, blockage of proapoptotic and cell cycle activities, and strong inhibition of cell migration and invasion than that induced by free TPL in MCF-7 and MDA-MB-231 cells. Importantly, TPL/NPs also showed higher efficacy in shrinking tumor size and blocking lung metastasis with decreased systemic toxicity in a 4T1 breast cancer mouse model at an equivalent or lower TPL dosage compared with that of free TPL. Histological immunofluorescence and immunohistochemical analyses in tumor and lung tissue revealed that TPL/NPs induced a high level of apoptosis and suppressed expression of matrix metalloproteinases, which contributed to inhibiting tumor growth and pulmonary metastasis.

Conclusion: Collectively, our results demonstrate that TPL/NPs, which combine tumor active targeting and pH/redox-responsive drug release with proapoptotic and antimobility effects, represent a promising candidate in halting breast cancer progression and metastasis while minimizing systemic toxicity.
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http://dx.doi.org/10.1186/s12951-021-00934-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220850PMC
June 2021

The complete mitogenome sequence of the hawk moth, subsp. (Lepidoptera: Sphingidae) from Zhejiang Province, China.

Mitochondrial DNA B Resour 2021 Jun 7;6(7):1880-1882. Epub 2021 Jun 7.

College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, Zhejiang, China.

The sphingid, subsp. is a common hawk moth distributed in southeast Asia and Australian regions. Although barcode analyses have been published, its complete mitogenome sequence has not been deciphered. In this study, the complete mitogenome of (GeneBank accession no. MW539688) was sequenced using Illumina HiSeq X Ten system for mitogenome-based phylogenetic analysis. The mitogenome was 15,354 bp in length and comprises 13 protein-coding genes (PCGs), two ribosomal RNA (rRNA) genes, and 22 transfer RNAs (tRNAs) with the typical gene order and orientation of Sphingidae mitogenomes. The nucleotide composition of majority strand is 41.2% for A, 7.4% for G, 12.0% for C, and 39.4% for T, with an A + T content of 80.6%. Phylogenetic analysis using the 13 PCGs fully resolved in a clade with , , and , with high nodal support both by Bayesian inference and maximum-likelihood methods, forming the Macroglossini monophyletic group.
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http://dx.doi.org/10.1080/23802359.2021.1934152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189079PMC
June 2021

Circ_0013359 facilitates the tumorigenicity of melanoma by regulating miR-136-5p/RAB9A axis.

Open Life Sci 2021 22;16(1):482-494. Epub 2021 May 22.

Department of Orthopedics, Weichang Hospital of Traditional Chinese Medicine, Chengde, Hebei, China.

Background: Circular RNAs play crucial roles in tumor occurrence and progression. This research aimed to explore the role and potential mechanism of hsa_circ_0013359 (circ_0013359) in melanoma.

Methods: The levels of circ_0013359, microRNA-136-5p (miR-136-5p), and member RAS oncogene family (RAB9A) in melanoma tissues and cells were detected using quantitative reverse transcriptase-polymerase chain reaction or western blot. Cell proliferation, apoptosis, cell cycle, cell migration, and invasion were evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2--tetrazolium bromide assay, colony formation assay, flow cytometry, and transwell assay. Glycolysis was determined by detecting glucose consumption, lactate production, and extracellular acidification rate. The levels of hexokinase 2 and lactate dehydrogenase A were examined by western blot. The targeting relationship between miR-136-5p and circ_0013359 or RAB9A was confirmed by dual-luciferase reporter assay. Xenograft experiments were used to analyze tumor growth .

Results: Circ_0013359 and RAB9A levels were increased, while the miR-136-5p level was reduced in melanoma tissues and cells. Circ_0013359 knockdown inhibited proliferation, migration, invasion, and glycolysis and promoted apoptosis and cycle arrest in A875 and SK-MEL-1 cells. Circ_0013359 sponged miR-136-5p to regulate melanoma progression. In addition, miR-136-5p suppressed melanoma progression by targeting RAB9A. Besides, circ_0013359 silencing inhibited tumor growth .

Conclusion: Depletion of circ_0013359 hindered melanoma progression by regulating miR-136-5p/RAB9A axis.
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http://dx.doi.org/10.1515/biol-2021-0030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8142382PMC
May 2021

Entrapment of Macrophage-Target Nanoparticles by Yeast Microparticles for Rhein Delivery in Ulcerative Colitis Treatment.

Biomacromolecules 2021 06 21;22(6):2754-2767. Epub 2021 May 21.

State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu 611130, China.

In this study, we developed an advanced colitis-targeted nanoparticles (NPs)-into-yeast cell wall microparticles (YPs) drug delivery system for ulcerative colitis (UC) therapy. In brief, YPs entrap hyaluronic acid (HA), and polyethylenimine (PEI) modified rhein (RH)-loaded ovalbumin NPs (HA/PEI-RH NPs) to form HA/PEI-RH NYPs. YPs can make HA/PEI-RH NPs pass through gastric environment stably and be degraded by β-glucanase to promote drug release from HA/PEI-RH NYPs in the colon. Cellular uptake evaluation confirmed that HA/PEI-RH NPs could specifically target and enhance the uptake rate via HA ligands. In biodistribution studies, HA/PEI-RH NYPs were able to efficiently accumulate in the inflammed colon in mice. In vivo experiments revealed that the HA/PEI-RH NYPs could significantly alleviate inflammation by inhibiting the TLR4/MyD88/NF-κB signaling pathway. Therefore, HA/PEI-RH NYPs have advantages of good gastric stability, β-glucanase-sensitive release ability, macrophage-targeted ability, and anti-UC effects. These advantages indicate YPs-entrapped multifunctional NPs are a promising oral drug delivery system for UC therapy.
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http://dx.doi.org/10.1021/acs.biomac.1c00425DOI Listing
June 2021

Mechanisms of Gegen Qinlian Pill to ameliorate irinotecan-induced diarrhea investigated by the combination of serum pharmacochemistry and network pharmacology.

J Ethnopharmacol 2021 Aug 11;276:114200. Epub 2021 May 11.

School of Medicine, Chengdu University, Chengdu, 610106, China. Electronic address:

Ethnopharmacological Relevance: Traditional Chinese medicine suggests the use of natural extracts and compounds is a promising strategy to prevent irinotecan (CPT-11)-induced gut toxicity and resulting diarrhea. Previous work from our lab indicated the protective effect of Gegen Qinlian decoction; given this, we further speculated that Gegen Qinlian Pill (GQP) would exhibit similar therapeutic effects. The effective material basis as well as potential mechanisms underlying the effect of GQP for the treatment of CPT-11-induced diarrhea have not been fully elucidated.

Aim Of The Study: The application of natural extracts or compounds derived from Chinese medicine is deemed to a promising strategy to prevent irinotecan (CPT-11)-induced gut toxicity. The aim of this study was to investigated the beneficial effects of GQP on CPT-11-induced gut toxicity and further explored its anti-diarrheal mechanism.

Methods: First, the beneficial effect of GQP in alleviating diarrhea in mice following CPT-11 administration was investigated. We also obtained the effective ingredients in GQP from murine serum samples using HPLC-Q-TOF-MS analysis. Based on these active components, we next established an interaction network linking "compound-target-pathway". Finally, a predicted mechanism of action was obtained using in vivo GQP validation based on Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses.

Results: A total of 19, GQP-derived chemical compounds were identified in murine serum samples. An interaction network linking "compound-target-pathway" was then established to illuminate the interaction between the components present in serum and their targets that mitigated diarrhea. These results indicated GQP exerted a curative effect on diarrhea and diarrhea-related diseases through different targets, which cumulatively regulated inflammation, oxidative stress, and proliferation processes.

Conclusion: Taken together, this study provides a feasible strategy to elucidate the effective constituents in traditional Chinese medicine formulations. More specifically, this work detailed the basic pharmacological effects and underlying mechanism behind GQP's effects in the treatment of CPT-11-induced gut toxicity.
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http://dx.doi.org/10.1016/j.jep.2021.114200DOI Listing
August 2021

Large-scale MoSSemonolayers synthesized by confined-space CVD.

Nanotechnology 2021 Jun 7;32(35). Epub 2021 Jun 7.

Engineering Research Center of IoT Technology Applications (Ministry of Education), Department of Electronic Engineering, Jiangnan University, Wuxi 214122, People's Republic of China.

Alloy engineering is efficient in modulating the electronic structure and physical and chemical properties of Transition metal dichalcogenides (TMDs). Here, we develop an efficient and simple confined-space CVD strategy by using a smaller quartz boat nested in a larger quartz boat for the preparation of ternary alloy MoSSemonolayers on SiO/Si substrates with controllable composition. The effect of hydrogen ratio of the mixed carrier gas (Ar/H) on the resultant flakes are systematically investigated. A hydrogon ratio of 15% is demonstrated to be the most appropriate to synthesize large size (more than 400m) single crystalline MoSSealloy monolayers. The composition of the alloy can also be changed in a full range (2= 0-2) by changing the weight ratio of Se and S powder. The as-grown monolayer MoSSealloys present continuously high crystal quality in terms of Raman and PL measurements. Furthermore, to visible light (532 nm), the MoSSebased photodetectors display wonderful photoresponse with a fast response of less than 50 ms. Our work may be usedful in directing the synthesis of TMDs alloys as well as their optoelectronic applications.
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http://dx.doi.org/10.1088/1361-6528/ac0026DOI Listing
June 2021

Calcium pectinate and hyaluronic acid modified lactoferrin nanoparticles loaded rhein with dual-targeting for ulcerative colitis treatment.

Carbohydr Polym 2021 Jul 27;263:117998. Epub 2021 Mar 27.

State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu, 611130, China. Electronic address:

Herein, dual-bioresponsive of Rhein (RH) in promoting colonic mucous damage repair and controlling inflammatory reactions were combined by the dual-targeting (intestinal epithelial cells and macrophages) oral nano delivery strategy for effective therapy of ulcerative colitis (UC). Briefly, two carbohydrates, calcium pectinate (CP) and hyaluronic acid (HA) were used to modify lactoferrin (LF) nanoparticles (NPs) to encapsulate RH (CP/HA/RH-NPs). CP layer make CP/HA/RH-NPs more stable and protect against the destructive effects of the gastrointestinal environment and then release HA/RH-NPs to colon lesion site. Cellular uptake evaluation confirmed that NPs could specifically target and enhance the uptake rate via LF and HA ligands. in vivo experiments revealed that CP/HA/RH-NPs significantly alleviated inflammation by inhibiting the TLR4/MyD88/NF-κB signaling pathway and accelerated colonic healing. Importantly, with the help of CP, this study was the first to attempt for LF as a targeting nanomaterial in UC treatment and offers a promising food-based nanodrug in anti-UC.
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http://dx.doi.org/10.1016/j.carbpol.2021.117998DOI Listing
July 2021

Neutrophil extracellular traps induced by pro-inflammatory cytokines enhance procoagulant activity in NASH patients.

Clin Res Hepatol Gastroenterol 2021 Apr 10:101697. Epub 2021 Apr 10.

Department of Hematology, The First Affiliated Hospital, Harbin Medical University, Harbin Heilongjiang, China; Department of Research, VA Boston Healthcare System, Harvard Medical School, Boston, MA, USA; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 1400 VFW Parkway, West Roxbury, Boston, MA 02132, USA. Electronic address:

Background: Nonalcoholic steatohepatitis (NASH) patients are at a high risk of developing venous thromboembolism, with a high rate of morbidity and mortality. The role of neutrophil extracellular traps (NETs) in procoagulant activity (PCA) in patients with NASH remains unclear. Our study aimed to investigate the formation of NETs in NASH patients stimulated by specific pro-inflammatory factors. Moreover, we evaluated the pivotal role of NETs in the induction of hypercoagulability in NASH and the interaction between NETs and endothelial injury.

Method: The levels of the NETs biomarkers were evaluated in the plasma samples of 27 NASH patients and 18 healthy subjects. The formation of NETs was visualized using immunofluorescence microscopy. The PCA of the NETs was assessed using coagulation time, purified coagulation complex, and fibrin formation assays. Confocal microscopy was further used to evaluate the interactions between the NETs and HUVECs.

Results: The levels of NETs markers in the plasma of NASH patients were significantly higher than healthy controls. NETs derived from NASH enhanced thrombin and fibrin formation and significantly reduced CT (p<0.05). The mixture of IL-6 and TNF-α triggered the NETs release in the plasma rather than them alone. Additionally, the NETs exerted cytotoxic effects on the endothelial cells, converting them to a procoagulant and pro-inflammatory phenotype, and DNase I could reverse these effects.

Conclusion: Our results revealed the primary role of NETs in promoting the hypercoagulable state in NASH patients. Methods that prevent the formation of NETs may be a novel approach for the prevention and treatment of NASH.
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http://dx.doi.org/10.1016/j.clinre.2021.101697DOI Listing
April 2021

Sublethal effects of bistrifluron on key biological traits, macronutrients contents and vitellogenin (SeVg) expression in Spodoptera exigua (Hübner).

Pestic Biochem Physiol 2021 May 23;174:104802. Epub 2021 Feb 23.

State Key Laboratory Breeding Base for Zhejiang Sustainable Pest and Disease Control, Zhejiang Academy of Agricultural Sciences, Institute of Plant Protection and Microbiology, Hangzhou 310021, PR China. Electronic address:

The beet armyworm, Spodoptera exigua, is a highly polyphagous pest originated from Southeast Asia but has spread globally, attacking economically important crops and fruits. Bistrifluron insecticide is one of the highly active insect growth regulators that has been reported to inhibit development and longevity in other lepidopteran species and could be used in the control of S. exigua. In the present study, the age-stage, two-sex life table technique was applied to assess the sublethal effects of bistrifluron on biological traits and vitellogenin gene (SeVg) expression when 2nd instar larvae fed to sublethal concentrations (LC, LC and LC) of bistrifluron. Mean generation time from eggs to adults was longer at LC (37.79 ± 0.81 d) and LC (37.04 ± 0.72) compared to the LC (36.89 ± 0.63 d) and control groups (36.07 ± 0.38 d). Fecundity of female at LC (279.17 ± 42.8 eggs), LC (347 ± 35.4 eggs) and LC (411.58 ± 42.38 eggs) were significantly lower than the control treatment (532.47 ± 7.13). Furthermore, the lower intrinsic rates of increase (LC; r = 0.1207 ± 0.009, LC; r = 0.1329 ± 0.009 and LC; r = 0.14398 ± 0.009 compared to the control r = 0.164 ± 0.0076), was observed along with significantly extended mean generation times (LC; T = 34.825 ± 0.317 days, LC; T = 33.27 ± 0.368 days and LC; T = 31.899 ± 0.398 days compared to the control 30.927 ± 0.255 days). Furthermore, the contents of energy reserve macronutrients (carbohydrate, lipid and protein) significantly reduced in dose and time dependent manner in treated insects as compared to control. Furthermore, the expression level of SeVg mRNA significantly decreased by 43.8% in the female adults when one-day-old second instar larvae were treated with sublethal concentrations of bistrifluron in comparison with the control. Documenting these sublethal effects is a vital, and often overlooked factor, in assessing the overall efficacy of insecticides in the management of pest populations.
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http://dx.doi.org/10.1016/j.pestbp.2021.104802DOI Listing
May 2021

Saponins Modulate the Inflammatory Response and Improve IBD-Like Symptoms via TLR/NF-[Formula: see text]B and MAPK Signaling Pathways.

Am J Chin Med 2021 7;49(4):925-939. Epub 2021 Apr 7.

Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macao 999078, P. R. China.

saponins (PNS) are the main active ingredients of (Burk) F. H. Chen, which are used as traditional Chinese medicine for thousands of years and have various clinical effects, including anti-inflammation, anti-oxidation, and cardiovascular protection. Inflammatory bowel disease (IBD) is a complex gastrointestinal inflammatory disease that cannot be cured completely nowadays. The anti-inflammatory and protective effects of PNS were analyzed and in dextran sulfate sodium (DSS)-induced colitis mouse model. PNS inhibited the release of nitric oxide (NO), tumor necrosis factor-[Formula: see text] (TNF-[Formula: see text], interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) in Pam3CSK4-induced RAW 264.7 macrophages. In the animal study, compared with DSS-induced mice, PNS reduced the expression of pro-inflammatory cytokines (TNF-[Formula: see text], IL-6, and MCP-1) in the colon tissues. Furthermore, PNS treatment led to a remarkable reduction in the activation of the inhibitor of nuclear factor kappa-B kinase [Formula: see text]/[Formula: see text] (IKK[Formula: see text]/[Formula: see text], I[Formula: see text]B[Formula: see text] and p65 induced by DSS. On the other hand, PNS inhibited the phosphorylation of c-Jun N-terminal kinase (JNK), p38, and extracellular regulated protein kinase 1/2 (ERK1/2). Taken together, our results suggested that PNS conferred profound protection for colitis mice through the downregulation of mitogen-activated protein kinase (MAPK) and NF-[Formula: see text]B signaling pathways, which were associated with reducing inflammatory responses, alleviating tissue damage, and maintaining of intestinal integrity and functionality.
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http://dx.doi.org/10.1142/S0192415X21500440DOI Listing
April 2021

Key Factors of Opening Gated Community in Urban Area: A Case Study of China.

Int J Environ Res Public Health 2021 03 25;18(7). Epub 2021 Mar 25.

Department of Civil Engineering, College of Engineering and Physical Sciences, Aston University, Birmingham B4 7ET, UK.

Gated communities are the most popular residential pattern in the urban areas of China. However, along with the increasing population density in urban areas, this pattern may have negative influences on people's daily lives, such as traffic jams. To avoid the negative influences, the government has encouraged residents to open their gated communities; however, few positive actions have been taken. With this background, this study aims to explore the key factors in residents' willingness to open their gated communities. To start with, a total of 26 potential factors were identified based on a comprehensive literature review. Then, a questionnaire was designed and distributed to collect empirical data. Furthermore, logistic regression was employed to analyze the collected data. Based on the derived results, it was revealed that concerns are different between male and female residents. Male residents regarded "community safety" and "property management" as having a significant impact on their decision to open a gated community, while female residents paid more attention to the factor of "proprietary equity". The results of this study could provide valuable references that enable the government to better understand residents' underlying concerns and to make relevant policy decisions.
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http://dx.doi.org/10.3390/ijerph18073401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037551PMC
March 2021

Synthesis, Preclinical Evaluation, and First-in-Human PET Study of Quinoline-Containing PSMA Tracers with Decreased Renal Excretion.

J Med Chem 2021 04 30;64(7):4179-4195. Epub 2021 Mar 30.

Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, China.

The prostate-specific membrane antigen (PSMA) is considered to be an excellent theranostic target of prostate cancer (PCa). In this study, three F-labeled PSMA tracers with a more lipophilic quinoline functional spacer were designed, synthesized, and evaluated based on the Glu-Ureido-Lys binding motif. The effect of structure-related lipophilic difference on distribution and excretion of these tracers in vitro and in vivo (cells, rodent, primate, and human) was investigated by comparing with [F]DCFPyL. There is no significant correlation between the renal elimination and the lipophilicity of the tracers in all species. However, the higher the lipophilicity of tracer, the higher the radioactivity accumulation in the liver of primate and human, and the less radioactivity is to excrete to the bladder with urine. The screened tracer [F], with a value of 4.58 nM, displayed notable low bladder retention and demonstrated good imaging properties in patients with PCa.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00117DOI Listing
April 2021

Redox-sensitive carrier-free nanoparticles self-assembled by disulfide-linked paclitaxel-tetramethylpyrazine conjugate for combination cancer chemotherapy.

Theranostics 2021 20;11(9):4171-4186. Epub 2021 Feb 20.

College of Materials Science and Engineering, Nanjing Tech Universit`y, Nanjing 211816, People's Republic of China.

Combinations of two or more therapeutic agents targeting different signaling pathways involved in tumor progression can have synergistic anticancer effects. However, combination chemotherapies are greatly limited by the different pharmacokinetics, tumor targeting, and cellular uptake capacities of the combined drugs. We have previously demonstrated the potential synergistic efficacy of paclitaxel (PTX) and the natural anti-angiogenic agent tetramethylpyrazine (TMP) for suppressing ovarian carcinoma growth. An efficient, facile, and smart nanosystem to deliver PTX and TMP simultaneously is greatly desired. We constructed a redox-sensitive nanosystem based on the amphiphilic PTX-ss-TMP conjugate, in which PTX and TMP are linked by a disulfide bond. We characterized the structure of the drug conjugate by H NMR and LC-MS, and then prepared PTX-ss-TMP NPs by a one-step nanoprecipitation method. We investigated the redox sensitivity, tumor-targeting ability, anticancer efficacy, and anti-angiogenesis activity of PTX-ss-TMP NPs and . The amphiphilic PTX-ss-TMP conjugate readily self-assembled into stable nanoparticles in aqueous solution with a low critical association concentration of 1.35 µg/mL, well-defined spherical structure, small particle size (152 nm), high drug loading, redox-responsive drug release, high biocompatibility, and high storage stability. In cancer cells pretreated with GSH-OEt, PTX-ss-TMP NPs exhibited higher cytotoxicity, apoptosis rate, and cell-cycle arrest than monotherapy or combination therapy with free drugs, which was attributed to their improved cellular uptake and rapid intracellular drug release. Additionally, PTX-ss-TMP NPs also had a stronger anti-angiogenesis effect in HUVECs than free drug, which was mediated by VEGFR2-involved downstream signals. Finally, PTX-ss-TMP NPs showed tumor-specific accumulation and excellent antitumor activity in A2780 xenograft mice compared with free drug. These and results provide clear evidence that this redox-responsive carrier-free nanosystem with intrinsic amphiphilicity has great potential for combination cancer chemotherapy.
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http://dx.doi.org/10.7150/thno.42260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7977472PMC
July 2021

Effect of methyl terminal and ethylene bridging groups on porous organosilicate glass films: FTIR, ellipsometric porosimetry, luminescence dataset.

Data Brief 2021 Apr 18;35:106895. Epub 2021 Feb 18.

North China University of Technology, Beijing, China.

A dataset in this report is regarding an article, "A detailed ellipsometric porosimetry and positron annihilation spectroscopy study of porous organosilicate glass films with various ratios of methyl terminal and ethylene bridging groups" [1]. The data of porous organosilicate glass (OSG) low-k films was obtained by Fourier-Transform Infrared spectroscopy (FTIR), Ellipsometric Porosimetry (EP), Photoluminescence (PL) Spectroscopy. The data shows that the mechanical properties of OSG low-k films are principally controlled by introducing both terminal methyl and bridging organic groups, and porosity with proper pore size. The dataset presented here gives additional details regarding properties of carbon bridged OSGs presented in the paper [1]. Also, the data may give the impact of both terminal methyl and bridging ethylene groups on as deposited and thermally cured OSG films. Particularly, we added some details about FTIR, EP (especially related to calculation of the internal surface area) and UV induced luminescence. The data allow to test experimental and theoretical investigations of OSG low-k materials that might use in microelectronic fabrication industry and also might be used to extend beyond the analysis reported in the accompanying manuscript, and may aid for other applications of OSG materials.
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http://dx.doi.org/10.1016/j.dib.2021.106895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921473PMC
April 2021

Integrated serum pharmacochemistry and network pharmacological analysis used to explore possible anti-rheumatoid arthritis mechanisms of the Shentong-Zhuyu decoction.

J Ethnopharmacol 2021 Jun 3;273:113988. Epub 2021 Mar 3.

State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China. Electronic address:

Ethnopharmacological Relevance: Shentong-Zhuyu decoction (STZYD) has been recognized by the Chinese National Administration of Traditional Chinese Medicine (TCM) as a classic TCM formula. Use of STZYD has shown a satisfactory clinical therapeutic outcome for rheumatoid arthritis (RA); despite this, its bioactive chemical composition and relevant mechanism(s) of this action have not been clearly elucidated.

Aim Of The Study: To explore the bioactive chemical composition of STZYD used for RA treatment and its possible mechanism(s) of action.

Materials And Methods: Serum pharmacochemistry mediated by the UPLC-Q-Exactive MS/MS method was employed to identify the absorbed phytochemical compounds in serum derived from STZYD, which were commonly considered as the potential bioactive compounds. And then, these components were used to construct a compound-target network for RA using a network pharmacology approach, to predict the possible biological targets of STZYD along with potential signaling pathways. Afterwards, we established a Complete Freund's adjuvant (CFA)-induced RA rat model, and observed the anti-RA effect of STZYD by a series of indexes, including foot swelling, ankle diameter, arthritis score, morphological and radiographic analysis, serum inflammatory factors, and histopathological analysis of synovial tissues. Particularly, the predicted pathway by the combination of serum pharmacochemistry and network pharmacology was further validated using RT-qPCR, Western blot, and immunohistochemical analyses in animal experiment.

Results: Totally, 38 compounds derived from STZYD have been identified by serum sample analysis. Based on it, 387 genes related to these identified compounds in STZYD and 3807 genes related to RA were collected by network pharmacology. Critically, KEGG analysis indicated that the PI3K/AKT signaling pathway was recommended as one of the main pathway related to anti-RA effect of STZYD. Experimentally, STZYD significantly alleviated CFA-induced arthritis without any visible side-effects. Compared to the RA model group without any treatment, the treatment of STZYD significantly reduced the expression of both mRNA and protein targets in the PI3K/AKT signaling pathway. Furthermore, this result was also corroborated by immunohistochemistry analysis. All these studies could effectively corroborate the predicted result as above, suggested that the feasibility of this integrated strategy.

Conclusion: This study provided a useful strategy to identify bioactive compounds and the potential mechanisms for TCM formula by integrating serum pharmacochemistry and network pharmacology.
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http://dx.doi.org/10.1016/j.jep.2021.113988DOI Listing
June 2021

H19 Promotes HCC Bone Metastasis Through Reducing Osteoprotegerin Expression in a Protein Phosphatase 1 Catalytic Subunit Alpha/p38 Mitogen-Activated Protein Kinase-Dependent Manner and Sponging microRNA 200b-3p.

Hepatology 2021 Jul 9;74(1):214-232. Epub 2021 May 9.

Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background And Aims: Bone is the second most frequent site of metastasis for HCC, which leads to an extremely poor prognosis. HCC bone metastasis is typically osteolytic, involving the activation of osteoclasts. Long noncoding RNA H19 plays an important role in the pathogenesis of human cancers. Nonetheless, the mechanism underlying the participation of H19 in HCC bone metastasis remains unclear.

Approach And Results: The current study established a mouse HCC bone metastasis model by using serial intracardiac injection and cell isolation to obtain cells with distinct bone metastasis ability. H19 was highly expressed in these cells and in clinical HCC bone metastasis specimens. Both osteoclastogenesis in vitro and HCC bone metastasis in vivo were promoted by H19 overexpression, whereas these processes were suppressed by H19 knockdown. H19 overexpression attenuated p38 phosphorylation and further down-regulated the expression of osteoprotegerin (OPG), also known as osteoclastogenesis inhibitory factor. However, up-regulated OPG expression as well as suppressed osteoclastogenesis caused by H19 knockdown were recovered by p38 interference, indicating that p38 mitogen-activated protein kinase (MAPK)-OPG contributed to H19-promoted HCC bone metastasis. Furthermore, we demonstrated that H19 inhibited the expression of OPG by binding with protein phosphatase 1 catalytic subunit alpha (PPP1CA), which dephosphorylates p38. SB-203580-mediated inactivation of p38MAPK reversed the down-regulation of HCC bone metastasis caused by H19 knockdown in vivo. Additionally, H19 enhanced cell migration and invasion by up-regulating zinc finger E-box binding homeobox 1 through the sequestration of microRNA (miR) 200b-3p.

Conclusions: H19 plays a critical role in HCC bone metastasis by reducing OPG expression, which is mediated by the PPP1CA-induced inactivation of the p38MAPK pathway; and H19 also functions as a sponge for miR-200b-3p.
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http://dx.doi.org/10.1002/hep.31673DOI Listing
July 2021

De Novo Transcriptomic Analyses Revealed Some Detoxification Genes and Related Pathways Responsive to Noposion Yihaogong 5% EC (Lambda-Cyhalothrin 5%) Exposure in Third-Instar Larvae.

Insects 2021 Feb 3;12(2). Epub 2021 Feb 3.

State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Institute of Plant Protection and Microbiology, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China.

The fall armyworm, (J.E. Smith) (Lepidoptera: Noctuidae), is a polyphagous, invasive insect pest which causes significant losses in important crops wherever it has spread. The use of pesticides in agriculture is a key tool in the management of many important crop pests, including , but continued use of insecticides has selected for various types of resistance, including enzyme systems that provide enhanced mechanisms of detoxification. In the present study, we analyzed the de novo transcriptome of larvae exposed to Noposion Yihaogong 5% emulsifiable concentrate (EC) insecticide focusing on detoxification genes and related pathways. Results showed that a total of 1819 differentially expressed genes (DEGs) were identified in larvae after being treated with Noposion Yihaogong 5% EC insecticide, of which 863 were up- and 956 down-regulated. Majority of these differentially expressed genes were identified in numerous Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, including metabolism of xenobiotics and drug metabolism. Furthermore, many of genes involved in detoxification pathways influenced by lambda-cyhalothrin stress support their predicted role by further co-expression network analysis. Our RT-qPCR results were consistent with the DEG's data of transcriptome analysis. The comprehensive transcriptome sequence resource attained through this study enriches the genomic platform of , and the identified DEGs may enable greater molecular underpinnings behind the insecticide-resistance mechanism caused by lambda-cyhalothrin.
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http://dx.doi.org/10.3390/insects12020132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913311PMC
February 2021
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