Publications by authors named "Panpan Zhang"

258 Publications

Dynamically Crosslinked Dry Ion-Conducting Elastomers for Soft Iontronics.

Adv Mater 2021 Jun 21:e2101396. Epub 2021 Jun 21.

CAS Center for Excellence in Nanoscience, Beijing Key Laboratory of Micro-Nano Energy and Sensor, Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, Beijing, 101400, China.

Soft ionic conductors show great promise in multifunctional iontronic devices, but currently utilized gel materials suffer from liquid leakage or evaporation issues. Here, a dry ion-conducting elastomer with dynamic crosslinking structures is reported. The dynamic crosslinking structures endow it with combined advantageous properties simultaneously, including high ionic conductivity (2.04 × 10 S cm at 25 °C), self-healing capability (96% healing efficiency), stretchability (563%), and transparency (78%). With this ionic conductor as the electrode, two soft iontronic devices (electroluminescent devices and triboelectric nanogenerator tactile sensors) are realized with entirely self-healing and stretchable capabilities. Due to the absence of liquid materials, the dry ion-conducting elastomer shows wide operational temperature range, and the iontronic devices achieve excellent stability. These findings provide a promising strategy to achieve highly conductive and multifunctional soft dry ionic conductors, and demonstrate their great potential in soft iontronics or electronics.
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http://dx.doi.org/10.1002/adma.202101396DOI Listing
June 2021

Clinicopathological features and lymph node and distant metastasis patterns in patients with gastroenteropancreatic mixed neuroendocrine-non-neuroendocrine neoplasm.

Cancer Med 2021 Jun 10. Epub 2021 Jun 10.

Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Cancer Hospital and Institute, Beijing, China.

Objective: Owing to its rarity and heterogeneity, the biological behavior and optimal therapeutic management of mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) have not been established. Herein, we aimed to evaluate the clinicopathological characteristics and metastatic patterns of MiNEN.

Methods: Continuous clinicopathological data of MiNEN patients treated at our hospital were retrospectively collected and analyzed.

Results: This study had enrolled 169 patients since January 2010 to January 2020. Pathological components were assessed in 129 patients with MiNEN (76.3%), and a focal (non-)neuroendocrine component was observed in 40 patients (23.7%; <30% of the tumor). Among the enrolled patients, 80 underwent surgical removal of the primary tumor and lymph nodes (LNs), and 34 with distant metastasis underwent biopsy of both primary tumor and metastatic lesions. In patients with LN metastasis, 68.8% (55/80) exhibited a pure component of either neuroendocrine (NE) or adenocarcinoma/squamous carcinoma (AS) in metastatic LNs, while 20% (16/80) showed different components in different LNs, and only 11.2% (9/80) exhibited both NE and AS components in the same LN. In patients with distant metastases, 26.5% (9/34) possessed coexisting NE and AS components in the distant metastases, 70.6% (24/34) were regarded as a pure NE component, and 2.9% (1/34) were comprised of a pure AS component.

Conclusion: Lymph node and distant metastases exhibited distinct metastatic patterns in patients with MiNEN. The major pathological component in regional LNs may have influenced the proportion of the two components within the primary tumor, but distant metastases were dominated by the NE component.
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http://dx.doi.org/10.1002/cam4.4031DOI Listing
June 2021

Proteomic analyses of plasma-derived exosomes in immunoglobulin (Ig) G4-related disease and their potential roles in B cell differentiation and tissue damage.

J Autoimmun 2021 Jun 6;122:102650. Epub 2021 Jun 6.

Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, State Key Laboratory of Complex Severe and Rare Diseases, Beijing, China. Electronic address:

Objective: To investigate the proteomic profiles of plasma exosomes isolated from patients with immunoglobulin (Ig) G4-related disease (IgG4-RD) and to determine their potential roles in B cell differentiation and tissue damage.

Methods: One hundred untreated IgG4-RD patients and 135 sex- and age-matched healthy controls (HCs) were enrolled in this study. A combination of liquid chromatography-tandem mass spectrometry (LC-MS/MS) and tandem mass tag (TMT)-label quantitation was used for proteomic profiling. Differentially expressed proteins were validated by Western blot, enzyme-linked immunosorbent assay (ELISA) and real-time quantitative PCR (RT-qPCR) analyses. B cell activation, apoptosis, differentiation and reactive oxygen species (ROS) production were analyzed by flow cytometry. We also analyzed the correlations between differentially expressed complement proteins and laboratory parameters.

Results: A total of 178 differentially expressed proteins were identified in plasma exosomes in IgG4-RD patients compared with HCs, and these proteins were enriched predominantly in the complement cascade pathway. Furthermore, reduced expression levels of complement components C3 and C5 in IgG4-RD were correlated with clinical parameters. Following stimulation with IgG4-RD plasma exosomes, the percentages of naïve B cells decreased, while those of memory B cells and plasmablasts increased; the levels of cytochrome c, somatic (CYCS) and downstream complement system activation also increased. Moreover, ROS production was greater in B cells of IgG4-RD patients than in those of HCs. In affected submandibular glands, the BCR signalling pathway was activated, and exosomes were enriched.

Conclusion: Proteomic profiling revealed that plasma exosome proteins may participate in the pathogenesis of IgG4-RD through complement activation and may be involved in B cell differentiation and activation of the B cell auto-oxidative damage pathway.
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http://dx.doi.org/10.1016/j.jaut.2021.102650DOI Listing
June 2021

Synergistic Stain Removal Achieved by Controlling the Fractions of Light and Thermo Responsive Components in the Dual-Responsive Copolymer Immobilized on Cotton Fabrics by Cross-Linker.

ACS Appl Mater Interfaces 2021 Jun 3;13(23):27372-27381. Epub 2021 Jun 3.

Key Laboratory of Advanced Textile Materials & Manufacturing Technology, Ministry of Education, Zhejiang Sci-Tech University, 310018 Hangzhou, P. R. China.

Enhanced synergistic stain removal is realized by tailoring the comonomer fractions of a light- and thermo-dual responsive copolymer, which is immobilized on cotton fabrics by a cross-linker. The copolymer poly(acrylamide azobenzene--ethylene glycol methacrylate--triethylene glycol methyl ether methacrylate), denoted P(AAAB--EGMA--MEOMA), is prepared by the ATRP polymerization method. The present molar ratio for these monomers is 1:2:17. Because of the existence of the light-responsive AAAB unit, the transition temperature of its aqueous solution under UV radiation is shifted to 39 °C, which is 2 °C higher than that in ambient conditions. This increase is caused by the trans-cis isomerization from the azobenzene groups, indicating an increased hydrophilicity of P(AAAB--EGMA--MEOMA) under UV radiation. After being immobilized onto cotton fabrics by a cross-linker, they are also dual-responsive. The equilibrium swelling ratio (ESR) of the cotton fabrics is further increased after UV radiation. Compared to our former investigation, the reduction of the AAAB molar fraction from 0.1 to 0.05 causes an increase of the ESR value by 10%. Moreover, the stain removal efficiency of the cotton fabrics immobilized with P(AAAB--EGMA--MEOMA) by cross-linker is also significantly improved under UV radiation. The hydrophilicity of the copolymer mainly from the MEOMA units is crucial to the cleaning capability. Additionally lowering the attachment between stain and the copolymer coating on the cotton fabrics by trans-cis isomerization in those AAAB units also favors the cleaning. Hence, the stain removal is strongly improved by optimizing the fraction of light- versus thermo-responsive components in the copolymer, which can profoundly reduce the consumption of chemical detergents and energy during laundry.
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http://dx.doi.org/10.1021/acsami.1c03290DOI Listing
June 2021

Design, synthesis and structure-activity relationships of novel N11-, C12- and C13-substituted 15-membered homo-aza-clarithromycin derivatives against various resistant bacteria.

Bioorg Chem 2021 Aug 18;113:104992. Epub 2021 May 18.

Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Wenhua Road, Jinan 250012, PR China. Electronic address:

Bacterial infections are still the main significant problem of public health in the world, and their elimination will greatly rely on the discovery of antibacterial drugs. In the processes of our searching for novel macrolide derivatives with excellent activity against sensitive and resistant bacteria, three series of novel N11-, C12- and C13-substituted 15-membered homo-aza-clarithromycin derivatives were designed and synthesized as Series A, B and C by creatively opening the lactone ring of clarithromycin (CAM), introducing various 4-substituted phenyl-1H-1,2,3-triazole side chains at the N11, C12 or C13 position of CAM and macrolactonization. The results from their in vitro antibacterial activity demonstrated that compounds 20c, 20d and 20f displayed not only the most potent activity against S. aureus ATCC25923 with the MIC values of 0.5, 0.5 and 0.5 µg/mL, but also greatly improved activity against B. subtilis ATCC9372 with the MIC values of less than or equal to 0.25, 0.25 and 0.25 µg/mL, respectively. In particular, compound 11g exhibited the strongest antibacterial effectiveness against all the tested resistant bacterial strains and had well balanced activity with the MIC values of 4-8 µg/mL. Further study on minimum bactericidal concentration and kinetics confirmed that compound 11g possessed a bacteriostatic effect on bacterial proliferation. Moreover, the results of molecular docking revealed an potential additional binding force between compound 11g and U790 in addition to the normal binding force of macrolide skeleton, which may explain why this compound performed the most potent activity against resistant bacteria. The results of cytotoxic assay indicated that compounds 20c, 20d and 20f were non-toxic to human breast cancer MCF-7 cells at its effective antibacterial concentration.
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http://dx.doi.org/10.1016/j.bioorg.2021.104992DOI Listing
August 2021

Surface-Modified Phthalocyanine-Based Two-Dimensional Conjugated Metal-Organic Framework Films for Polarity-Selective Chemiresistive Sensing.

Angew Chem Int Ed Engl 2021 May 25. Epub 2021 May 25.

Technische Universitat Dresden, Department of Chemistry and Food Chemistry, Mommsenstrasse 4, 01062, Dresden, GERMANY.

Two-dimensional conjugated metal-organic frameworks (2D c -MOFs) are emerging as new-generation electroactive materials for chemiresistive sensors. However, selective sensing with fast response/recovery remains a challenge. Here, we report for the first time phthalocyanine-based Ni 2 [MPc(NH) 8 ] 2D c -MOF films as active layers for polarity-selective chemiresisitors toward water and volatile organic compounds (VOCs). We demonstrate that surface-hydrophobic-modification by grafting aliphatic alkyl chains on 2D c -MOF films reduces the amount of diffused analytes into the MOF backbone, thus resulting in a considerably accelerated recovery progress (from ~ 50 to ~ 10 s) during humidity sensing. Toward VOCs, the sensors deliver a polarity-selective response among alcohols while no signal is recorded for the low-polar aprotic hydrocarbons. Typically, the octadecyltrimethoxysilane-modified Ni 2 [MPc(NH) 8 ] based sensor displays high-performance methanol sensing with fast response (36 s)/recovery (13 s) and a detection limit as low as 10 ppm, which surpass the reported chemiresistors based on MOFs, conducting polymers, metal disulfides, and black phosphorus at room temperature.
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http://dx.doi.org/10.1002/anie.202104461DOI Listing
May 2021

Design, synthesis and evaluation of novel 9-arylalkyl-10-methylacridinium derivatives as highly potent FtsZ-targeting antibacterial agents.

Eur J Med Chem 2021 Oct 28;221:113480. Epub 2021 Apr 28.

Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Wenhua Road, Jinan, 250012, China. Electronic address:

With the increasing incidence of antibiotic resistance, new antibacterial agents having novel mechanisms of action hence are in an urgent need to combat infectious diseases caused by multidrug-resistant (MDR) pathogens. Four novel series of substituted 9-arylalkyl-10-methylacridinium derivatives as FtsZ inhibitors were designed, synthesized and evaluated for their antibacterial activities against various Gram-positive and Gram-negative bacteria. The results demonstrated that they exhibited broad-spectrum activities with substantial efficacy against MRSA and VRE, which were superior or comparable to the berberine, sanguinarine, linezolid, ciprofloxacin and vancomycin. In particular, the most promising compound 15f showed rapid bactericidal properties, which avoid the emergence of drug resistance. However, 15f showed no inhibitory effect on Gram-negative bacteria but biofilm formation study gave possible answers. Further target identification and mechanistic studies revealed that 15f functioned as an effective FtsZ inhibitor to alter the dynamics of FtsZ self-polymerization, which resulted in termination of the cell division and caused cell death. Further cytotoxicity and animal studies demonstrated that 15f not only displayed efficacy in a murine model of bacteremia in vivo, but also no significant hemolysis to mammalian cells. Overall, this compound with novel skeleton could serve as an antibacterial lead of FtsZ inhibitor for further evaluation of drug-likeness.
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http://dx.doi.org/10.1016/j.ejmech.2021.113480DOI Listing
October 2021

Bulked segregant CGT-Seq-facilitated map-based cloning of a powdery mildew resistance gene originating from wild emmer wheat (Triticum dicoccoides).

Plant Biotechnol J 2021 May 5. Epub 2021 May 5.

State Key Laboratory of Plant Cell and Chromosome Engineering, Institute of Genetics and Developmental Biology, The Innovative Academy of Seed Design, Chinese Academy of Sciences, Beijing, China.

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http://dx.doi.org/10.1111/pbi.13609DOI Listing
May 2021

Molecular dissection of maize seedling salt tolerance using a genome-wide association analysis method.

Plant Biotechnol J 2021 May 2. Epub 2021 May 2.

Beijing Key Laboratory of Maize DNA Fingerprinting and Molecular Breeding, Maize Research Center, Beijing Academy of Agriculture and Forestry Sciences (BAAFS), Beijing, China.

Salt stress is a major devastating abiotic factor that affects the yield and quality of maize. However, knowledge of the molecular mechanisms of the responses to salt stress in maize is limited. To elucidate the genetic basis of salt tolerance traits, a genome-wide association study was performed on 348 maize inbred lines under normal and salt stress conditions using 557 894 single nucleotide polymorphisms (SNPs). The phenotypic data for 27 traits revealed coefficients of variation of >25%. In total, 149 significant SNPs explaining 6.6%-11.2% of the phenotypic variation for each SNP were identified. Of the 104 identified quantitative trait loci (QTLs), 83 were related to salt tolerance and 21 to normal traits. Additionally, 13 QTLs were associated with two to five traits. Eleven and six QTLs controlling salt tolerance traits and normal root growth, respectively, co-localized with QTL intervals reported previously. Based on functional annotations, 13 candidate genes were predicted. Expression levels analysis of 12 candidate genes revealed that they were all responsive to salt stress. The CRISPR/Cas9 technology targeting three sites was applied in maize, and its editing efficiency reached 70%. By comparing the biomass of three CRISPR/Cas9 mutants of ZmCLCg and one zmpmp3 EMS mutant with their wild-type plants under salt stress, the salt tolerance function of candidate genes ZmCLCg and ZmPMP3 were confirmed. Chloride content analysis revealed that ZmCLCg regulated chloride transport under sodium chloride stress. These results help to explain genetic variations in salt tolerance and provide novel loci for generating salt-tolerant maize lines.
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http://dx.doi.org/10.1111/pbi.13607DOI Listing
May 2021

Identification of Extrachromosomal Circular Forms of Active Transposable Elements Using Mobilome-Seq.

Methods Mol Biol 2021 ;2250:87-93

IRD, UMR232 DIADE, University of Montpellier, Montpellier, France.

Active transposable elements (TEs) generate insertion polymorphisms that can be detected through genome resequencing strategies. However, these techniques may have limitations for organisms with large genomes or for somatic insertions. Here, we present a method that takes advantage of the extrachromosomal circular DNA (eccDNA) forms of actively transposing TEs in order to detect and characterize active TEs in any plant or animal tissue. Mobilome-seq consists in selectively amplifying and sequencing eccDNAs. It relies on linear digestion of genomic DNA followed by rolling circle amplification of circular DNA. Both active DNA transposons and retrotransposons can be identified using this technique.
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http://dx.doi.org/10.1007/978-1-0716-1134-0_7DOI Listing
June 2021

Exosomal MicroRNAs Mediating Crosstalk Between Cancer Cells With Cancer-Associated Fibroblasts and Tumor-Associated Macrophages in the Tumor Microenvironment.

Front Oncol 2021 1;11:631703. Epub 2021 Apr 1.

Shanghai Key Laboratory of Gynecology Oncology, Department of Gynecology and Obstetrics, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Exosomes are small extracellular vesicles containing diverse bioactive molecules. They play essential roles in mediating bidirectional interplay between cancer and stromal cells. Specific elements are selected into different types of exosomes via various mechanisms, including microRNAs (miRNAs), a subset of non-coding RNA that could epigenetically reprogram cells and modulate their activities. Cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) are two major types of stromal cells inhibiting immune response and facilitating tumor progression. Notably, accumulated studies provided critical evidence regarding the significance of exosomal miRNA-mediated intercellular crosstalk between cancer cells with TAMs and CAFs for tumor progression. This review aimed to summarize the current knowledge of cell-cell interactions between stromal and cancer cells conveyed by exosome-derived miRNAs. The findings might help find effective therapeutic targets of cancer.
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http://dx.doi.org/10.3389/fonc.2021.631703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049566PMC
April 2021

Clinical characteristics and outcome of IgG4-related disease with hypocomplementemia: a prospective cohort study.

Arthritis Res Ther 2021 04 7;23(1):102. Epub 2021 Apr 7.

Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology; State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital (PUMCH); Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, No.1 Shuai Fu Yuan, Dong Cheng District, Beijing, 100730, China.

Background: Immunoglobulin G4-related disease (IgG4-RD) is a newly recognized systemic, immune-mediated, and fibro-inflammatory disease. Hypocomplementemia was found in part of IgG4-RD patients especially in the setting of active disease.

Objectives: This study aimed to clarify the clinical features, treatment efficacy, and outcome in IgG4-RD patients with hypocomplementemia.

Methods: 312 IgG4-RD patients were recruited in our prospective cohort conducted in Peking Union Medical College Hospital. Patients were divided into hypocomplementemia group and normal complement group according to serum C3 and C4 levels measured at baseline before treatment. Low serum C3 levels (< 0.73 g/L) and/or C4 levels (< 0.10 g/L) were defined as hypocomplementemia. Demographic data, clinical characteristics, laboratory parameters, treatment, and outcome of two groups were analyzed and compared.

Results: Hypocomplementemia was identified in 65 (20.8%) cases of untreated IgG4-RD patients at baseline. The average age of hypocomplementemia group was 55.85 ± 10.89 years, with male predominance (72.3%). Compared with normal complement group, patients with hypocomplementemia were likely to have more involved organs, higher IgG4-RD responder index (IgG4-RD RI), and higher laboratory parameters such as counts of eosinophils, inflammatory markers, immunoglobulin G (IgG), IgG1, IgG3, IgG4, and IgE. In addition, lymph nodes, lacrimal gland, submandibular gland, parotid gland, paranasal sinus, bile ducts, and prostate gland were more commonly affected (p < 0.05). Serum C3 and C4 showed a significant positively correlation with each other. Both C3 and C4 were negatively correlated with the number of involved organs, IgG, IgG3, IgG4, and IgG4-RD RI, as well as positively correlated with IgA and hypersensitive C reactive protein (hsCRP). 64 (98.5%) patients responded quickly to initial therapy at a 3-month follow-up. Fifteen (23.1%) patients relapsed during follow-up with mean recurrence time of 14.2 ± 13.8 months. Compared with normal complement group, there was no significant difference of relapse rate in two groups (P = 0.401).

Conclusions: Clinical characteristics of IgG4-related disease with hypocomplementemia differ from normal complement group. Serum C3 and C4 at baseline before treatment could be biological markers for disease activity. IgG4-RD with hypocomplementemia responded well to treatment and had no significant difference of relapse rate in IgG4-RD with normal complement.
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http://dx.doi.org/10.1186/s13075-021-02481-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025345PMC
April 2021

Wearable Antifreezing Fiber-Shaped Zn/PANI Batteries with Suppressed Zn Dendrites and Operation in Sweat Electrolytes.

ACS Appl Mater Interfaces 2021 Apr 6;13(15):17608-17617. Epub 2021 Apr 6.

CAS Center for Excellence in Nanoscience, Beijing Key Laboratory of Micro-Nano Energy and Sensor, Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, Beijing 101400, China.

Fiber-shaped Zn batteries are promising candidates for wearable electronics owing to their high energy and low cost, but further studies are still required to address the issues related to detrimental Zn dendrite growth and limited low-temperature performances. Here, we report an antifreeze, long-life, and dendrite-free fiber-shaped Zn battery using both nanoporous Zn and polyaniline (PANI) electrodeposited on carbon nanofibers (CFs) as the cathode and anode, respectively. The fiber-shaped Zn anode achieves stable plating/stripping for 1000 mAh cm accumulative capacity with low polarization (30 mV) at a current density of 2 mA cm. The dendrite-free Zn electrodes also enable the stable cycling of the fiber battery with 75.1% capacity retention after 1000 cycles. With an antifreeze agent added in the gel electrolyte, the fiber battery maintains excellent performance at temperatures as low as -30 °C. Lastly, by utilizing the doping/dedoping mechanism of Cl in the PANI electrode, we achieve, for the first time, a Zn battery using human sweat as a harmless electrolyte. Our work provides a long-life and antifreeze fiber-shaped battery that is highly promising for future wearable energy storage devices.
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http://dx.doi.org/10.1021/acsami.1c02065DOI Listing
April 2021

A novel immune-related prognostic signature in epithelial ovarian carcinoma.

Aging (Albany NY) 2021 04 4;13(7):10289-10311. Epub 2021 Apr 4.

Department of Gynecology and Obstetrics, Shanghai Key Laboratory of Gynecology Oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.

The immune response is associated with the progression and prognosis of epithelial ovarian cancer (EOC). However, the roles of infiltrated immune cells and immune-related genes (IRGs) in EOC have not been reported comprehensively. In the current study, the differentially expressed genes (DEGs) were filtered based on the integrated gene expression data acquired from The University of California at Santa Cruz (UCSC) Genome Browser. Then, IRGs and transcriptional factors (TFs) were screened based on the ImmPort database and Cistrome database. A total of 501 differentially expressed IRGs, and 76 TFs were detected. A TF-mediated network was constructed by univariate Cox analysis to reveal the potential regulatory mechanisms of IRGs. Next, a nine immune-based prognostic risk model using nine IRGs (PI3, CXCL10, CXCL11, LCN6, CCL17, CCL25, MIF, CX3CR1, and CSPG5) was established. Based on the risk score worked out from the signature, the EOC patients could be classified into low-risk and high-risk groups. Furthermore, the immune landscapes, elevated by the cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) algorithm and the Tumor Immune Estimation Resource (TIMER) database, effectuated different patterns in two groups. Thus, an immune-based prognostic risk model of EOC elucidates the immune status in the tumor microenvironment, and hence, could be used for prognosis.
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http://dx.doi.org/10.18632/aging.202792DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064207PMC
April 2021

Rhizoma drynariae total flavonoids inhibit the inflammatory response and matrix degeneration via MAPK pathway in a rat degenerative cervical intervertebral disc model.

Biomed Pharmacother 2021 Jun 16;138:111466. Epub 2021 Mar 16.

School of Public Health, Anhui Medical University, Hefei 230032, Anhui, China; Anhui Provincial Key Laboratory of Population Health and Aristogenics, Hefei 230032, Anhui, China. Electronic address:

Rhizoma drynariae total flavonoids (RDTF) are extracted from Drynaria fortunei J. Sm (D. fortunei), which was a Chinese herb commonly used to treat fractures and bruises. Modern pharmacological studies indicate flavonoids have anti-inflammatory effect in clinical practice. However, its active ingredients and the mechanisms of action are far from clear. The present study aims to determine whether RDTF can protect against intervertebral disc degeneration in a rat cervical intervertebral disc model and investigate the associated molecular mechanisms. Sprague Dawley (SD) rats were randomized into five groups: control group (CG, n = 8), intervertebral disc degeneration group (NG, n = 8), low-dose RDTF-treated group (LG, n = 8), medium-dose RDTF-treated group (MG, n = 8), and high-dose RDTF-treated group (HG, n = 8). Hematoxylin and eosin (HE) staining, immunohistochemistry (IHC), immunofluorescence, ELISA, Western blot and quantitative real time PCR (qRT-PCR) assays were used to investigate inflammatory, catabolic factors and the latent regulatory mechanism of the effects of RDTF on intervertebral disc cells. HE staining showed disc degeneration in all groups except CG, and the function was restored after RDTF treatment. IHC, Western blot, qRT-PCR, immunofluorescence and ELISA results showed that RDTF prevented intervertebral disc degeneration by suppressing mitogen-activated protein kinase (MAPK) pathway, which reduced expression of intracellular matrix metalloproteinases (MMPs), such MMP3, MMP13, and inflammatory factors including interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α). Notably RDTF inhibited extracellular matrix (ECM) degeneration by increasing expression of aggrecan and collagen type II and preventing the upregulation of collagen type I and III. It suggests that RDTF has a potential therapeutic effect on cervical spondylosis.
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http://dx.doi.org/10.1016/j.biopha.2021.111466DOI Listing
June 2021

Caspase cleavage releases a nuclear protein fragment that stimulates phospholipid scrambling at the plasma membrane.

Mol Cell 2021 04 15;81(7):1397-1410.e9. Epub 2021 Mar 15.

Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Yoshida-Honmachi, Sakyoku, Kyoto 606-8501, Japan; Graduate School of Biostudies, Kyoto University, Konoe-cho, Yoshida, Sakyoku, Kyoto 606-8501, Japan; AMED-FORCE, Japanese Agency for Medical Research and Development, 1-7-1 Otemachi, Chiyodaku, Tokyo 100-0004, Japan; Center for Integrated Biosystems, Institute for Biomedical Sciences, Academia Sinica, Taipei, Taiwan. Electronic address:

Phospholipid scrambling in dying cells promotes phosphatidylserine exposure, a critical process for efferocytosis. We previously identified the Xkr family protein Xkr4 as a phospholipid-scrambling protein, but its activation mechanisms remain unknown. Here we show that Xkr4 is activated in two steps: dimer formation by caspase-mediated cleavage and structural change caused by activating factors. To identify the factors, we developed a new screening system, "revival screening," using a CRISPR sgRNA library. Applying this system, we identified the nuclear protein XRCC4 as the single candidate for the Xkr4 activator. Upon apoptotic stimuli, XRCC4, contained in the DNA repair complex, is cleaved by caspases, and its C-terminal fragment with an intrinsically disordered region is released into the cytoplasm. Protein interaction screening showed that the fragment interacts directly with the Xkr4 dimer to activate it. This study demonstrates that caspase-mediated cleavage releases a nuclear protein fragment for direct regulation of lipid dynamics on the plasma membrane.
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http://dx.doi.org/10.1016/j.molcel.2021.02.025DOI Listing
April 2021

Chisosiamens A-E, five new ring-intact limonoids with isomerized furan ring from the fruit of Chisocheton siamensis.

Fitoterapia 2021 Jun 1;151:104873. Epub 2021 Mar 1.

State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, People's Republic of China. Electronic address:

Five new ring-intact limonoids with isomerized furan ring, chisosiamens A-E (1-5), along with four known compounds (6-9) were isolated from the fruit of Chisocheton siamensis Craib. Their structures were elucidated based on 1D and 2D NMR spectroscopic data, HRESIMS, circular dichroism, and exciton chirality method. The biological activities screening showed that new limonoid 5 exhibited significant NO inhibitory activity in LPS-activated RAW 264.7 macrophages (IC: 10.13 ± 1.40 μM) and 1, 2, 5, and 9 effectively reversed the resistance in MCF-7/DOX cells with the range IC values of 10.20-15.06 μM (RI: 4.05-5.98).
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http://dx.doi.org/10.1016/j.fitote.2021.104873DOI Listing
June 2021

Development of a novel, fully human, anti-PCSK9 antibody with potent hypolipidemic activity by utilizing phage display-based strategy.

EBioMedicine 2021 Mar 26;65:103250. Epub 2021 Feb 26.

Department of Cell and Molecular Biology, School of Life Science and Technology, State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, China Pharmaceutical University, Nanjing 210009, P.R. China. Electronic address:

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates serum LDL cholesterol (LDL-C) levels by facilitating the degradation of the LDL receptor (LDLR) and is an attractive therapeutic target for hypercholesterolemia intervention. Herein, we generated a novel fully human antibody with favourable druggability by utilizing phage display-based strategy.

Methods: A potent single-chain variable fragment (scFv) named AP2M21 was obtained by screening a fully human scFv phage display library with hPCSK9, and performing two in vitro affinity maturation processes including CDR-targeted tailored mutagenesis and cross-cloning. Thereafter, it was transformed to a full-length Fc-silenced anti-PCSK9 antibody FAP2M21 by fusing to a modified human IgG1 Fc fragment with L234A/L235A/N297G mutations and C-terminal lysine deletion, thus eliminating its immune effector functions and mitigating mAb heterogeneity.

Findings: Our data showed that the generated full-length anti-PCSK9 antibody FAP2M21 binds to hPCSK9 with a K as low as 1.42 nM, and a dramatically slow dissociation rate (k, 4.68 × 10 s), which could be attributed to its lower binding energy (-47.51 kcal/mol) than its parent counterpart FAP2 (-30.39 kcal/mol). We verified that FAP2M21 potently inhibited PCSK9-induced reduction of LDL-C uptake in HepG2 cells, with an EC of 43.56 nM. Further, in hPCSK9 overexpressed C57BL/6 mice, a single tail i.v. injection of FAP2M21 at 1, 3 and 10 mg/kg, dose-dependently up-regulated hepatic LDLR levels, and concomitantly reduced serum LDL-C by 3.3% (P = 0.658, unpaired Student's t-test), 30.2% (P = 0.002, Mann-Whitney U-test) and 37.2% (P = 0.002, Mann-Whitney U-test), respectively.

Interpretation: FAP2M21 with potent inhibitory effect on PCSK9 may serve as a promising therapeutic agent for treating hypercholesterolemia and associated cardiovascular diseases.
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http://dx.doi.org/10.1016/j.ebiom.2021.103250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921758PMC
March 2021

Hypoglycemic activity of Origanum vulgare L. and its main chemical constituents identified with HPLC-ESI-QTOF-MS.

Food Funct 2021 Mar 25;12(6):2580-2590. Epub 2021 Feb 25.

National & Local Joint Engineering Research Center of High-throughput Drug Screening Technology, Hubei Province Key Laboratory of Biotechnology of Chinese Traditional Medicine, Hubei University, Wuhan 430062, P.R. China.

Origanum vulgare L. (O. vulgare) is an important medicine food homology in diabetes. The present study aimed to assess the hypoglycemic effect of the leaf extract of O. vulgare in HepG2 and HepG2-GFP-CYP2E1 (E47) cells, and disclose its potential active components by the HPLC-ESI-QTOF-MS method. Firstly, we evaluated the anti-diabetic capacity of the leaf extract of O. vulgare through inhibition of α-glucosidase activity, promotion of glucose uptake, inhibition of glycosylation and relieving of oxidative stress. Secondly, the promoter activity, the mRNA and protein expression of PEPCK and SREBP-1c, and the expression of CPY2E1 and GLUT2 in the O. vulgare mediated anti-diabetic capacity were analyzed in HepG2 and E47 cells. Finally, HPLC-ESI-QTOF-MS analysis was performed to identify the herb's main components under 280 nm irradiation. In vitro assays demonstrated that the extract inhibited α-glucosidase activity, promoted glucose uptake, inhibited glycosylation and relieved oxidative stress, which suggested that O. vulgare leaf extract has a strong hypoglycemic capacity. Moreover, mechanistic analysis also showed that the extract decreased the promoter activity and the mRNA and protein expression of PEPCK and SREBP-1c. In addition, the extract inhibited the expression of CPY2E1 and enhanced the expression of GLUT2. Moreover, the UV chromatogram at 280 nm showed six main peaks, identified as amburoside A (or 4-(3',4'-dihydroxybenzoyloxymethyl) phenyl O-β-d-glucopyranoside), luteolin 7-O-glucuronide, apigenin 7-O-glucuronide, rosmarinic acid, lithospermic acid and a novel compound, demethylbenzolignanoid, based on accurate MS data. This work supported the ethnopharmacological usage of O. vulgare as an antidiabetic herbal medicine or dietary supplement and identified its main phenolic compounds.
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http://dx.doi.org/10.1039/d0fo03166fDOI Listing
March 2021

HIF-1α downregulation of miR-433-3p in adipocyte-derived exosomes contributes to NPC progression via targeting SCD1.

Cancer Sci 2021 Apr 22;112(4):1457-1470. Epub 2021 Feb 22.

Department of Otorhinolaryngology Head and Neck Surgery, Affiliated Hospital of Nantong University, Nantong, China.

Resident adipocytes under a hypoxic tumor microenvironment exert an increasingly important role in cell growth, proliferation, and invasion in cancers. However, the communication between adipocytes and cancer cells during nasopharyngeal carcinoma (NPC) progression is poorly understood. Here, we demonstrate that hypoxic adipocyte-derived exosomes are key information carriers that transfer low expression of miR-433-3p into NPC cells. In addition, luciferase reporter assays detected that hypoxia inducible factor-1α (HIF-1α) induced miR-433-3p transcription through five binding sites at its promoter region. Concordantly, the low expression of miR-433-3p promoted proliferation, migration, and lipid accumulation in NPC cells via targeting stearoyl-CoA desaturase 1 (SCD1) are suggested by functional studies. Consistent with these findings, in tumor-bearing mice, NPC cells with low HIF-1α expression, high miR-433-3p expression, and low SCD1 expression were equally endowed with remarkably reduced potential of tumorigenesis. Collectively, our study highlights the critical role of the HIF-1α-miR-433-3p-SCD1 axis in NPC progression, which can serve as a mechanism-based potential therapeutic approach.
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http://dx.doi.org/10.1111/cas.14829DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019221PMC
April 2021

Ambient-Stable Two-Dimensional Titanium Carbide (MXene) Enabled by Iodine Etching.

Angew Chem Int Ed Engl 2021 Apr 10;60(16):8689-8693. Epub 2021 Mar 10.

Center for Advancing Electronics Dresden (cfaed), Faculty of Chemistry and Food Chemistry, Technische Universität Dresden, Mommsenstrasse 4, 01062, Dresden, Germany.

MXene (e.g., Ti C ) represents an important class of two-dimensional (2D) materials owing to its unique metallic conductivity and tunable surface chemistry. However, the mainstream synthetic methods rely on the chemical etching of MAX powders (e.g., Ti AlC ) using hazardous HF or alike, leading to MXene sheets with fluorine termination and poor ambient stability in colloidal dispersions. Here, we demonstrate a fluoride-free, iodine (I ) assisted etching route for preparing 2D MXene (Ti C T , T=O, OH) with oxygen-rich terminal groups and intact lattice structure. More than 71 % of sheets are thinner than 5 nm with an average size of 1.8 μm. They present excellent thin-film conductivity of 1250 S cm and great ambient stability in water for at least 2 weeks. 2D MXene sheets with abundant oxygen surface groups are excellent electrode materials for supercapacitors, delivering a high gravimetric capacitance of 293 F g at a scan rate of 1 mV s , superior to those made from fluoride-based etchants (<290 F g at 1 mV s ). Our strategy provides a promising pathway for the facile and sustainable production of highly stable MXene materials.
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http://dx.doi.org/10.1002/anie.202015627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048443PMC
April 2021

Self-Selective Multi-Terminal Memtransistor Crossbar Array for In-Memory Computing.

ACS Nano 2021 Jan 14;15(1):1764-1774. Epub 2021 Jan 14.

Department of Electrical and Computer Engineering, National University of Singapore, 117583, Singapore.

Two-terminal resistive switching devices are commonly plagued with longstanding scientific issues including interdevice variability and sneak current that lead to computational errors and high-power consumption. This necessitates the integration of a separate selector in a one-transistor-one-RRAM (1T-1R) configuration to mitigate crosstalk issue, which compromises circuit footprint. Here, we demonstrate a multi-terminal memtransistor crossbar array with increased parallelism in programming independent gate control, which allows computation at a dense cell size of 3-4.5 F and a minimal sneak current of 0.1 nA. Moreover, a low switching energy of 20 fJ/bit is achieved at a voltage of merely 0.42 V. The architecture is capable of performing multiply-and-accumulate operation, a core computing task for pattern classification. A high MNIST recognition accuracy of 96.87% is simulated owing to the linear synaptic plasticity. Such computing paradigm is deemed revolutionary toward enabling data-centric applications in artificial intelligence and Internet-of-things.
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http://dx.doi.org/10.1021/acsnano.0c09441DOI Listing
January 2021

Dynamic micelles with detachable PEGylation at tumoral extracellular pH for enhanced chemotherapy.

Asian J Pharm Sci 2020 Nov 3;15(6):728-738. Epub 2020 Jan 3.

Engineering Research Center for Biomedical Materials, School of Life Science, Anhui University, Hefei 230601, China.

Although surface PEGylation of nanomedicines can decrease serum protein adsorption , it also blocks uptake by tumor cells. This dilemma could be overcome by employing detachably PEGylated strategy at tumoral extracellular microenvironment to achieve improved cellular uptake while prolonged circulation times. Herein, the amphiphilic graft copolymers with pH-sensitive ortho ester-linked mPEG in side chains and polyurethanes in backbone, can self-assemble into the free and doxorubicin (DOX)-loaded micelles. The pH-sensitive micelles could undergo several characteristics as follows: (i) PEGylated shells for stability in sodium dodecyl sulfonate (SDS) solution; (ii) DePEGylation via degradation of ortho ester linkages at tumoral extracellular pH (6.5) for gradually dynamic size changes and effective release of DOX; and (iii) enhanced cellular uptake and cytotoxicity via positive DOX. Moreover, the dynamic micelles with detachable PEGylation could quickly penetrate the centers of SH-SY5Y multicellular spheroids (MCs) and strongly inhibit tumor growth and , and might be considered as promising and effective drug carriers in tumor therapy.
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http://dx.doi.org/10.1016/j.ajps.2019.11.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7750827PMC
November 2020

Improved efficiency of urine cell image segmentation using droplet microfluidics technology.

Cytometry A 2020 Dec 20. Epub 2020 Dec 20.

School of Medical Laboratory, Tianjin Medical University, Tianjin, China.

Recent advances in the recognition of biological samples using machine vision have made this technology increasingly important in research and detection. Image segmentation is an important step in this process. This study focuses on how to reduce the interference factors such as the overlap between different types (or within the same type) of urine cells according to microfluidics and improve the machine vision segmentation accuracy for cell images. In this study, we demonstrate that the platform can realize this hypothesis using urine cell image segmentation as an example application. We first discuss the reported urine cell droplet microfluidic chip system, which can realize the test conditions in which urine cells are encapsulated in the droplet and isolated from salt crystallization and/or bacteria and other urine-formed elements. Then, based on the analysis conditions set in the aforementioned experiment, the proportions of red blood cells, white blood cells, and squamous epithelial cells covered by various formed elements in the total urine cells in the same urine sample are measured. We simultaneously analyze the percentage of urine cells covered by salt crystallization and the incidence of overlapping between urine cells. Finally, the Otsu algorithm is used to segment the urine cell images encapsulated by the droplet and the urine cell images not encapsulated by the droplet, and the Dice, Jaccard, precision, and recall values are calculated. The results suggest that the method of encapsulating single cells based on droplets can improve the image segmentation effect without optimizing the algorithm.
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http://dx.doi.org/10.1002/cyto.a.24296DOI Listing
December 2020

UPLC-MS based plasma metabolomics and lipidomics reveal alterations associated with IgG4-related disease.

Rheumatology (Oxford) 2020 Dec 20. Epub 2020 Dec 20.

Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences.

Objective: The pathogenesis of IgG4-related disease (IgG4-RD) remains unclear. Metabolomic profiling of IgG4-RD patients offers an opportunity to identify novel pathophysiological targets and biomarkers. This study aims to identify potential plasma biomarkers associated with IgG4-RD.

Methods: Thirty newly diagnosed IgG4-RD patients, age-matched healthy controls and post-treated IgG4-RD patients were enrolled. Patients' clinical data, laboratory parameters and plasma were collected. Plasma was measured for ultraperformance liquid chromatography-tandem mass spectrometry based metabolomics and lipidomics profiling. Multivariate and univariate statistical analyses were conducted to identify potential biomarkers. The receiver operating characteristic and the correlations between biomarkers and clinical parameters were investigated.

Results: The plasma metabolites are altered among healthy controls, newly diagnosed IgG4-RD and post-treated IgG4-RD groups. Of the identified features, eight metabolites were significantly perturbed in the IgG4-RD group, including glyceric acid 1,3-biphosphate (1,3-BPG), uridine triphosphate (UTP), uridine diphosphate glucose (UDP-Glc) or uridine diphosphate galactose (UDP-Gal), lysophospholipids, linoleic acid derivatives and ceramides. Receiver operating characteristic analysis indicated that UTP, UDP-Glc/UDP-Gal and LysoPC (18:1) had high sensitivity and specificity in diagnosis of IgG4-RD. A Pearson correlation analysis showed that 1,3-BPG and UTP were strongly correlated with clinical parameters.

Conclusion: IgG4-RD patients have a unique plasma metabolomic profile compared with healthy controls. Our study suggested that metabolomic profiling may provide important insights into pathophysiology and testable biomarkers for diagnosis of IgG4-RD.
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http://dx.doi.org/10.1093/rheumatology/keaa775DOI Listing
December 2020

Sesamol alleviates chronic intermittent hypoxia-induced cognitive deficits via inhibiting oxidative stress and inflammation in rats.

Neuroreport 2021 01;32(2):105-111

Department of Respiratory and Critical Medicine, Tianjin Medical University General Hospital.

Chronic intermittent hypoxia (CIH) is a major pathophysiological feature of obstructive sleep apnea (OSA), which can cause oxidative stress and inflammation which can further impair the nervous system. Cognitive impairment is a common complication of the nervous system in OSA. Sesamol, a natural extract from Sesamum plants, is believed to have strong antioxidant and anti-inflammation capacity, which has a powerful neuroprotective function. But whether sesamol can improve CIH-induced cognitive impairment is unclear. This study aimed to explore whether sesamol can improve CIH-induced cognitive impairment and its relative mechanism in the model rats with OSA. Rats were exposed to CIH for 8 h a day for 2, 4, 6, and 8 weeks separately and concurrently were treated with sesamol (20 mg/kg/day, intraperitoneal). The Morris water maze (MWM) test was used to evaluate their learning and memory function. The activity of the superoxide dismutase (SOD) and the level of malondialdehyde were measured to evaluate the oxidative stress in the hippocampus of the rats. The levels of tumour necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) in the hippocampus were quantified to analyse neuroinflammation by ELISA. The MWM test showed that sesamol improved learning and memory impairment in CIH-exposed rats. We also found that the sesamol-treated CIH-exposed rats had significantly increased the activity of SOD, as well as reduced the level of malondialdehyde in the hippocampus. In addition, sesamol also reduced the levels of TNF-α and IL-1β in the hippocampus. These data show that sesamol is able to alleviate cognitive impairments in CIH-exposed rats, with its neuroprotective effects likely inhibiting oxidative stress and inflammation.
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http://dx.doi.org/10.1097/WNR.0000000000001564DOI Listing
January 2021

Somatostatin Analogs for Pancreatic Neuroendocrine Tumors: Any Benefit When Ki-67 Is ≥10%?

Oncologist 2021 04 29;26(4):294-301. Epub 2020 Dec 29.

Department of Endocrine Oncology University Medical Center Utrecht, The Netherlands.

Background: Long-acting somatostatin analogs (SSAs) are the primary first-line treatment of well-differentiated advanced gastroenteropancreatic neuroendocrine tumors (NETs), but data about their efficacy in pancreatic NETs (panNETs) with Ki-67 ≥10% are still limited.

Materials And Methods: To assess the clinical outcomes of advanced, nonfunctioning, well-differentiated panNETs with Ki-67 ≥10% receiving first-line long-acting SSAs in a real-world setting, we carried out a retrospective, multicenter study including patients treated between 2014-2018 across 10 centers of the NET CONNECT Network. The primary endpoints were time to next treatment (TNT) and progression-free survival (PFS), whereas overall survival (OS) and treatment safety were secondary endpoints.

Results: A total of 73 patients were included (68 grade [G]2, 5 G3), with liver metastases in 61 cases (84%). After a median follow-up of 36.4 months (range, 6-173), the median TNT and PFS were 14.2 months (95% confidence interval [CI], 11.6-16.2) and 11.9 months (95% CI, 8.6-14.1) respectively. No statistically significant difference was observed according to the somatostatin analog used (octreotide vs. lanreotide), whereas increased tumor grade (hazard ratio [HR], 4.4; 95% CI, 1.2-16.6; p = .04) and hepatic tumor load (HR, 2; 95% CI, 1-4; p = .03) were independently associated with shortened PFS. The median OS recorded was 86 months (95% CI, 56.8-86 months), with poor outcomes observed when the hepatic tumor burden was >25% (HR, 3.4; 95% CI, 1.2-10; p = .01). Treatment-related adverse events were reported in 14 patients, most frequently diarrhea.

Conclusion: SSAs exert antiproliferative activity in panNETs with Ki-67 ≥10%, particularly in G2 tumors, as well as when hepatic tumor load is ≤25%.

Implications For Practice: The results of the study call into question the antiproliferative activity of somatostatin analogs (SSAs) in pancreatic neuroendocrine tumors with Ki-67 ≥10%. Patients with grade 2 tumors and with hepatic tumor load ≤25% appear to derive higher benefit from SSAs. Prospective studies are needed to validate these results to optimize tailored therapeutic strategies for this specific patient population.
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http://dx.doi.org/10.1002/onco.13633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018333PMC
April 2021

Facile assembly of layer-interlocked graphene heterostructures as flexible electrodes for Li-ion batteries.

Faraday Discuss 2021 Apr 8;227:321-331. Epub 2020 Dec 8.

Center for Advancing Electronics Dresden (cfaed), Department of Chemistry and Food Chemistry, Technische Universität Dresden, 01062 Dresden, Germany.

Flexible electrodes with robust mechanical properties and high electrochemical performance are of significance for the practical implementation of flexible batteries. Here we demonstrate a general and straightforward co-assembly approach to prepare flexible electrodes, where electrochemically exfoliated graphene (EG) is exploited as the film former/conducting matrix and different binary metal oxides (LiTiO, LiCoO, LiMnO, LiFePO) are incorporated. The resultant EG-metal oxide hybrids exhibit a unique layer-interlocked structure, where the metal oxide is conformably wrapped by the highly flexible graphene. Due to numerous contact interphases generated between EG and the intercalated material, the hybrid films show high flexibility and can endure rolling, bending, folding and even twisting. When serving as the anode for Li-ion batteries, the freestanding EG-LiTiO hybrid presents a characteristic flat discharge plateau at 1.55 V (vs. Li/Li), indicating transformation of LiTiO to LiTiO. Small polarization, high rate capability and excellent cycling stability against mechanical bending are also demonstrated for the prepared EG-LiTiO hybrid. Finally, full cells composed of EG-LiTiO and EG-LiFePO hybrids show impressive cycling (98% capacity retention after 100 cycles at 1C) and rate performance (84% capacity retained at 2.5C). The straightforward co-assembly approach based on EG can be extended to other two-dimensional layered materials for constructing highly efficient flexible energy storage devices.
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http://dx.doi.org/10.1039/c9fd00120dDOI Listing
April 2021

Design and structural optimization of novel 2H-benzo[h]chromene derivatives that target AcrB and reverse bacterial multidrug resistance.

Eur J Med Chem 2021 Mar 27;213:113049. Epub 2020 Nov 27.

Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Wenhua Road, Jinan, 250012, China. Electronic address:

Drug efflux pumps have emerged as a new drug targets for the treatment of bacterial infections in view of its critical role in promoting multidrug resistance. Herein, novel chromanone and 2H-benzo[h]chromene derivatives were designed by means of integrated molecular design and structure-based pharmacophore modeling in an attempt to identify improved efflux pump inhibitors that target Escherichia coli AcrB. The compounds were tested for their efflux inhibitory activity, ability to inhibit efflux, and the effect on bacterial outer and inner membranes. Twenty-three novel structures were identified that synergized with antibacterials tested, inhibited Nile Red efflux, and acted specifically on the AcrB. Among them, WK2, WL7 and WL10 exhibiting broad-spectrum and high-efficiency efflux inhibitory activity were identified as potential ideal AcrB inhibitors. Molecular modeling further revealed that the strong π-π stacking interactions and hydrogen bond networks were the major contributors to tight binding of AcrB.
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http://dx.doi.org/10.1016/j.ejmech.2020.113049DOI Listing
March 2021

Influence of Coagulation Bath Temperature on the Structure and Dielectric Properties of Porous Polyimide Films in Different Solvent Systems.

ACS Omega 2020 Nov 10;5(46):29889-29895. Epub 2020 Nov 10.

Center for Composite Materials and Structures, Harbin Institute of Technology, Harbin 150001, People's Republic of China.

In this work, the effect of coagulation bath temperature in different solvent systems [1,4-butyrolactone (GBL)/,-dimethylacetamide (DMAC)] on the structure and dielectric properties of polyimide (PI) films was investigated for the first time. The solubility parameter was introduced to explain the formation process of porous PI films. The results showed that the changed tendency of the dielectric constant versus temperature is opposite for the single-solvent system and cosolvent system. For a single DMAC and GBL solvent, the dielectric constants of the films decreased with increasing temperature. In contrast, the dielectric constants increased with the increase in temperature for the GBL/DMAC cosolvent system. Moreover, the measured porosities were applied to estimate the dielectric constants of the PI films. This showed that the porosity increased with increasing temperature for a single-solvent system, while it decreased for a cosolvent system. Scanning electron microscopy images suggested that the variation trends are derived from the different influences of the temperature on the structure and morphology. Thus, this study reveals the effect of coagulation bath temperature on the structure and dielectric properties of porous PI films and provides the guidance for the design and optimization of architectures for high-performance porous films.
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http://dx.doi.org/10.1021/acsomega.0c04103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689915PMC
November 2020