Publications by authors named "Ziyi Wang"

217 Publications

Long noncoding RNA LINC01703 exacerbates the malignant properties of non-small-cell lung cancer by upregulating MACC1 in a microRNA-605-3p-mediated manner.

Oncol Res 2021 Sep 7. Epub 2021 Sep 7.

Long intergenic nonprotein coding RNA 1703 (LINC01703) has diagnostic significancein lung adenocarcinoma. However, its specific roles in non-small-cell lung cancer(NSCLC) and downstream mechanisms have not been investigated. In the current study,we characterized the role of LINC01703 in NSCLC malignancy and elucidated itsdetailed mechanism of action. LINC01703 expression was measured by qRT-PCR. Theregulatory effects of LINC01703 on the malignancy of NSCLC cells were assessed bymultiple functional experiments. The targeted interaction was confirmed by RNAimmunoprecipitation and luciferase reporter assays. Herein, overexpression ofLINC01703 in NSCLC was indicated in the TCGA database and further proven in ourcohort. Functional studies revealed that knocking down LINC01703 repressed cellproliferation, colony formation, migration and invasion in vitro, which wasaccompanied by the induction of apoptosis. The tumor growth of LINC01703-silencedcells was also inhibited in vivo. Mechanistic analyses revealed that LINC01703functioned as a competing endogenous RNA for microRNA-605-3p (miR-605-3p) inNSCLC cells, which thereby upregulated the miR-605-3p target metastasis associatedwith colon cancer 1 (MACC1). Rescue experiments highlighted that the regulatoryactions of LINC01703 ablation on NSCLC cells were abolished in response to miR-605-3p downregulation or MACC1 overexpression. In conclusion, LINC01703enhanced the aggressiveness of NSCLC cells by altering miR-605-3p/MACC1. Ourwork suggests the therapeutic potential of LINC01703/miR-605-3p/MACC1 in NSCLC.
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http://dx.doi.org/10.3727/096504021X16310057751016DOI Listing
September 2021

Direct Measurement of the Branching Fractions B(ψ(3686)→J/ψX) and B(ψ(3770)→J/ψX), and Observation of the State R(3760) in e^{+}e^{-}→J/ψX.

Phys Rev Lett 2021 Aug;127(8):082002

Istanbul Bilgi University, 34060 Eyup, Istanbul, Turkey.

We report a measurement of the observed cross sections of e^{+}e^{-}→J/ψX based on 3.21  fb^{-1} of data accumulated at energies from 3.645 to 3.891 GeV with the BESIII detector operated at the BEPCII collider. In analysis of the cross sections, we measured the decay branching fractions of B(ψ(3686)→J/ψX)=(64.4±0.6±1.6)% and B(ψ(3770)→J/ψX)=(0.5±0.2±0.1)% for the first time. The energy-dependent line shape of these cross sections cannot be well described by two Breit-Wigner (BW) amplitudes of the expected decays ψ(3686)→J/ψX and ψ(3770)→J/ψX. Instead, it can be better described with one more BW amplitude of the decay R(3760)→J/ψX. Under this assumption, we extracted the R(3760) mass M_{R(3760)}=3766.2±3.8±0.4  MeV/c^{2} , total width Γ_{R(3760)}^{tot}=22.2±5.9±1.4  MeV, and product of leptonic width and decay branching fraction Γ_{R(3760)}^{ee}B[R(3760)→J/ψX]=(79.4±85.5±11.7)  eV. The significance of the R(3760) is 5.3σ. The first uncertainties of these measured quantities are from fits to the cross sections and second systematic.
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http://dx.doi.org/10.1103/PhysRevLett.127.082002DOI Listing
August 2021

Analytical Performance Evaluation of Three Commercial Rapid Nucleic Acid Assays for SARS-CoV-2.

Infect Drug Resist 2021 14;14:3169-3174. Epub 2021 Aug 14.

Department of Laboratory Medicine, and Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.

Purpose: To cope with the SARS-CoV-2 epidemic, several rapid nucleic acid assays have been approved for use, but the analytical performance has not been well evaluated. In this report, two key performance parameters, analytical sensitivity (limit of detection) and reproducibility, of three approved rapid nucleic acid assays were assessed using heat-inactivated SARS-CoV-2 culture supernatants quantified by digital PCR.

Methods: The LOD (limit of detection) and reproducibility of three approved rapid nucleic acid assays using their own instruments were assessed, while the LOD and reproducibility of two assays on a 7500 Real-Time instrument were assessed at the same time.

Results: Using their own instruments, 100% of samples with 1150 copies/mL viral RNA could be detected by the Da An and Coyote assays, while 90% of samples could be detected by the Ustar assay; yet, for 525 copies/mL and 287.5 copies/mL viral RNA, the detection rate of the Ustar assay was higher than that of either the Da An or Coyote assays. However, the three assays did not produce statistically significant results with the three different concentrations of viral RNA (P=0.46, 0.46 and 0.46). Using a 7500 Real-Time instrument, Da An and Coyote assays did not produce statistically significant results with the 1150, 525 and 287.5 copies/mL viral RNA (P>0.99, >0.99 and >0.99). The positive and negative detection rates of the three assays in the intra- and inter-assay stages were 100% on both their own instruments and the 7500 real-time PCR instrument.

Conclusion: Positive or strongly positive samples can be detected by the rapid nucleic acid assay, but the analytical performance should be optimized, and comprehensive evaluations are also required.
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http://dx.doi.org/10.2147/IDR.S321227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8374845PMC
August 2021

O-GlcNAcylation drives calcium signaling toward osteoblast differentiation: A bioinformatics-oriented study.

Biofactors 2021 Aug 21. Epub 2021 Aug 21.

Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.

This study aimed to reveal the possible mechanisms by which O-linked-N-acetylglucosaminylation (O-GlcNAcylation) regulates osteoblast differentiation using a series of bioinformatics-oriented experiments. To examine the influence of O-GlcNAcylation levels on osteoblast differentiation, osteoblastic MC3T3-E1 cells were treated with O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) inhibitors. Correlations between the levels of O-GlcNAcylation and the expression of osteogenic markers as well as OGT were evaluated by qPCR and western blotting. The O-GlcNAcylated proteins assumed to correlate with Runx2 expression were retrieved from several public databases and used for further bioinformatics analysis. Following the findings of the bioinformatics analysis, intracellular calcium ([Ca ] ) was monitored in the cells treated with OGT and OGA inhibitors using a confocal laser-scanning microscope (CLS). The interaction effect between O-GlcNAcylation and [Ca ] on osteogenic marker expression was determined using stable OGT knockdown MC3T3-E1 cells. O-GlcNAcylation was positively associated with osteoblast differentiation. The time-course profile of global O-GlcNAcylated proteins showed a distinctive pattern with different molecular weights during osteoblast differentiation. The expression pattern of several O-GlcNAcylated proteins was significantly similar to that of Runx2 expression. Bioinformatic analysis of the retrieved Runx2-related-O-GlcNAcylated-proteins revealed the importance of [Ca ] . CLS showed that alteration of O-GlcNAcylation rapidly changed [Ca ] in MC3T3-E1 cells. O-GlcNAcylation and [Ca ] showed an interaction effect on the expression of osteogenic markers. OGT knockdown disrupted the [Ca ] -induced expression changes of osteogenic markers. O-GlcNAcylation interacts with [Ca ] and elicits osteoblast differentiation by regulating the expression of osteogenic markers.
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http://dx.doi.org/10.1002/biof.1774DOI Listing
August 2021

Extracellular vesicles of P. gingivalis-infected macrophages induce lung injury.

Biochim Biophys Acta Mol Basis Dis 2021 Nov 11;1867(11):166236. Epub 2021 Aug 11.

Department of Oral Healthcare Promotion, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.

Periodontal diseases are common inflammatory diseases that are induced by infection with periodontal bacteria such as Porphyromonas gingivalis (Pg). The association between periodontal diseases and many types of systemic diseases has been demonstrated; the term "periodontal medicine" is used to describe how periodontal infection/inflammation may impact extraoral health. However, the molecular mechanisms by which the factors produced in the oral cavity reach multiple distant organs and impact general health have not been elucidated. Extracellular vesicles (EVs) are nano-sized spherical structures secreted by various types of cells into the tissue microenvironment, and influence pathophysiological conditions by delivering their cargo. However, a detailed understanding of the effect of EVs on periodontal medicine is lacking. In this study, we investigated whether EVs derived from Pg-infected macrophages reach distant organs in mice and influence the pathophysiological status. EVs were isolated from human macrophages, THP-1 cells, infected with Pg. We observed that EVs from Pg-infected THP-1 cells (Pg-inf EVs) contained abundant core histone proteins such as histone H3 and translocated to the lungs, liver, and kidneys of mice. Pg-inf EVs also induced pulmonary injury, including edema, vascular congestion, inflammation, and collagen deposition causing alveoli destruction. The Pg-inf EVs or the recombinant histone H3 activated the NF-κB pathway, leading to increase in the levels of pro-inflammatory cytokines in human lung epithelial A549 cells. Our results suggest a possible mechanism by which EVs produced in periodontal diseases contribute to the progression of periodontal medicine.
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http://dx.doi.org/10.1016/j.bbadis.2021.166236DOI Listing
November 2021

Genetic factors may affect the severity of COVID-19.

Int J Cardiol 2021 11 30;342:126-127. Epub 2021 Jul 30.

Department of Respiratory and Critical Care Medicine, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Institute of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou, Guangdong 510120, China. Electronic address:

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http://dx.doi.org/10.1016/j.ijcard.2021.07.058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323502PMC
November 2021

Hyperpolarized Xe MRI and Spectroscopy of Gas-Exchange Abnormalities in Nonspecific Interstitial Pneumonia.

Radiology 2021 Oct 27;301(1):211-220. Epub 2021 Jul 27.

From the Department of Radiology (D.G.M., J.K., B.D., J.G.M.), Center for In Vivo Microscopy (D.G.M., B.D.), Department of Biomedical Engineering (E.A.B., Z.W., B.D.), Department of Medicine (L.M., C.B., H.P.M., R.T.), and Department of Medical Physics (B.D.), Duke University, DUMC Box 3302, Durham, NC 27710.

Background Recent studies demonstrate that antifibrotic drugs previously reserved for idiopathic pulmonary fibrosis (IPF) may slow progression in other interstitial lung diseases (ILDs), creating an urgent need for tools that can sensitively assess disease activity, progression, and therapy response across ILDs. Hyperpolarized xenon 129 (Xe) MRI and spectroscopy have provided noninvasive measurements of regional gas-exchange abnormalities in IPF. Purpose To assess gas exchange function using Xe MRI in a group of study participants with nonspecific interstitial pneumonia (NSIP) compared with healthy control participants. Materials and Methods In this prospective study, participants with NSIP and healthy control participants were enrolled between November 2017 and February 2020 and underwent Xe MRI and spectroscopy. Quantitative imaging provided three-dimensional maps of ventilation, interstitial barrier uptake, and transfer into the red blood cell (RBC) compartment. Spectroscopy provided parameters of the static RBC and barrier uptake compartments, as well as cardiogenic oscillations in RBC signal amplitude and chemical shift. Differences between NSIP and healthy control participants were assessed using the Wilcoxon rank-sum test. Results Thirty-six participants with NSIP (mean age, 57 years ± 11 [standard deviation]; 27 women) and 15 healthy control participants (mean age, 39 years ± 18; two women) were evaluated. Participants with NSIP had no difference in ventilation compared with healthy control participants (median, 4.4% [first quartile, 1.5%; third quartile, 8.7%] vs 6.0% [first quartile, 2.8%; third quartile, 6.9%]; = .91), but they had a higher barrier uptake (median, 6.2% [first quartile, 1.8%; third quartile, 23.9%] vs 0.53% [first quartile, 0.33%; third quartile, 2.9%]; = .003) and an increased RBC transfer defect (median, 20.6% [first quartile, 11.6%; third quartile, 27.8%] vs 2.8% [first quartile, 2.3%; third quartile, 4.9%]; < .001). NSIP participants also had a reduced ratio of RBC-to-barrier peaks (median, 0.24 [first quartile, 0.19; third quartile, 0.31] vs 0.57 [first quartile, 0.52; third quartile, 0.67]; < .001) and a reduced RBC chemical shift (median, 217.5 ppm [first quartile, 217.0 ppm; third quartile, 218.0 ppm] vs 218.2 ppm [first quartile, 217.9 ppm; third quartile, 218.6 ppm]; = .001). Conclusion Participants with nonspecific interstitial pneumonia had increased barrier uptake and decreased red blood cell (RBC) transfer compared with healthy controls measured using xenon 129 gas-exchange MRI and reduced RBC-to-barrier ratio and RBC chemical shift measured using spectroscopy. © RSNA, 2021 See also the editorial by Wild in this issue.
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http://dx.doi.org/10.1148/radiol.2021204149DOI Listing
October 2021

Roles for B[a]P and FICZ in subchondral bone metabolism and experimental temporomandibular joint osteoarthritis via the AhR/Cyp1a1 signaling axis.

Sci Rep 2021 Jul 21;11(1):14927. Epub 2021 Jul 21.

Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8525, Japan.

Bone loss due to smoking represents a major risk factor for fractures and bone osteoporosis. Signaling through the aryl hydrocarbon receptor (AhR) and its ligands contributes to both bone homeostasis and inflammatory diseases. It remains unclear whether the same AhR signaling axis affects the temporomandibular joint (TMJ). The aim of this study was to investigate possible mechanisms which mediate bone loss in the TMJ due to smoking. In particular, whether benzo[a]pyrene (B[a]P), a carcinogen of tobacco smoke, induces expression of the AhR target gene, Cyp1a1, in mandibular condyles. Possible functions of an endogenous ligand of FICZ, were also investigated in a TMJ-osteoarthritis (OA) mouse model. B[a]P was administered orally to wild-type and AhR mice and bone metabolism was subsequently examined. TMJ-OA was induced in wild-type mice with forceful opening of the mouth. Therapeutic functions of FICZ were detected with μCT and histology. Exposure to B[a]P accelerated bone loss in the mandibular subchondral bone. This bone loss manifested with osteoclastic bone resorption and upregulated expression of Cyp1a1 in an AhR-dependent manner. In a mouse model of TMJ-OA, FICZ exhibited a dose-dependent rescue of mandibular subchondral bone loss by repressing osteoclast activity. Meanwhile, in vitro, pre-treatment with FICZ reduced RANKL-mediated osteoclastogenesis. B[a]P regulates mandibular subchondral bone metabolism via the Cyp1a1. The AhR ligand, FICZ, can prevent TMJ-OA by regulating osteoclast differentiation.
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http://dx.doi.org/10.1038/s41598-021-94470-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295293PMC
July 2021

Self-assembly of photosensitive and radiotherapeutic peptide for combined photodynamic-radio cancer therapy with intracellular delivery of miRNA-139-5p.

Bioorg Med Chem 2021 Aug 10;44:116305. Epub 2021 Jul 10.

Dept. of Radiology, Affiliated Yancheng School of Clinical Medicine of Nanjing Medical University, PR China. Electronic address:

Background: A significant challenge in cancer therapy is to maximize the therapeutic efficacy and minimize the side effects. In the past decade, a lot of nanoparticles have been used as the carriers for efficient drug delivery.

Methods And Results: This study was to prepare R9 modified with I-labeled cRGD and ce6 which self-assembled with miR-139-5p to form nanoparticles (Ce6-R9-I-RGD-MNPs), and to further take advantage of the enhanced permeability and retention (EPR) effect of radiolabeled nanoparticles to realize the integration of tumor diagnosis and treatment. We successfully synthesized and represented it, saline and serum stability experiments demonstrating good stability. Moreover, Ce6-R9-I-RGD-MNPs showed superior tumor targeting and the effect of combined photodynamic therapy (PDT) and radiotherapy treatment in vivo and vitro.

Conclusion: The pathological results further confirmed that the therapeutic doses of Ce6-R9-I-RGD-MNPs cause pathological changes of tumor tissues while showing minimal toxicity to normal tissues.
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http://dx.doi.org/10.1016/j.bmc.2021.116305DOI Listing
August 2021

Hyperpolarized Xe Magnetic Resonance Imaging for Functional Avoidance Treatment Planning in Thoracic Radiation Therapy: A Comparison of Ventilation- and Gas Exchange-Guided Treatment Plans.

Int J Radiat Oncol Biol Phys 2021 Jul 13. Epub 2021 Jul 13.

Department of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina.

Purpose: To present a methodology to use pulmonary gas exchange maps to guide functional avoidance treatment planning in radiation therapy (RT) and evaluate its efficacy compared with ventilation-guided treatment planning.

Methods And Materials: Before receiving conventional RT for non-small cell lung cancer, 11 patients underwent hyperpolarized Xe gas exchange magnetic resonance imaging to map the distribution of xenon in its gas phase (ventilation) and transiently bound to red blood cells in the alveolar capillaries (gas exchange). Both ventilation and gas exchange maps were independently used to guide development of new functional avoidance treatment plans for every patient, while adhering to institutional dose-volume constraints for normal tissues and target coverage. Furthermore, dose-volume histogram (DVH)-based reoptimizations of the clinical plan, with reductions in mean lung dose (MLD) equal to the functional avoidance plans, were created to serve as the control group. To evaluate each plan (regardless of type), gas exchange maps, representing end-to-end lung function, were used to calculate gas exchange-weighted MLD (fMLD), gas exchange-weighted volume receiving ≥20 Gy (fV20), and mean dose in the highest gas exchanging 33% and 50% volumes of lung (MLD-f33% and MLD-f50%). Using each clinically approved plan as a baseline, the reductions in functional metrics were compared for ventilation-optimization, gas exchange optimization, and DVH-based reoptimization. Statistical significance was determined using the Freidman test, with subsequent subdivision when indicated by P values less than .10 and post hoc testing with Wilcoxon signed rank tests to determine significant differences (P < .05). Toxicity modeling was performed using an established function-based model to estimate clinical significance of the results.

Results: Compared with DVH-based reoptimization of the clinically approved plans, gas exchange-guided functional avoidance planning more effectively reduced the gas exchange-weighted metrics fMLD (average ± SD, -78 ± 79 cGy for gas exchange, compared with -45 ± 34 cGy for DVH-based; P = .03), MLD-f33% (-135 ± 136 cGy, compared with -52 ± 47 cGy; P = .004), and MLD-f50% (-96 ± 95 cGy, compared with -47 ± 40 cGy; P = .01). Comparing the 2 functional planning types, gas exchange-guided planning more effectively reduced MLD-f33% compared with ventilation-guided planning (-64 ± 95; P = .009). For some patients, gas exchange-guided functional avoidance plans demonstrated clinically significant reductions in model-predicted toxicity, more so than the accompanying ventilation-guided plans and DVH-based reoptimizations.

Conclusion: Gas exchange-guided planning effectively reduced dose to high gas exchanging regions of lung while maintaining clinically acceptable plan quality. In many patients, ventilation-guided planning incidentally reduced dose to higher gas exchange regions, to a lesser extent. This methodology enables future prospective trials to examine patient outcomes.
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http://dx.doi.org/10.1016/j.ijrobp.2021.07.002DOI Listing
July 2021

Panicle Apical Abortion 3 Controls Panicle Development and Seed Size in Rice.

Rice (N Y) 2021 Jul 15;14(1):68. Epub 2021 Jul 15.

Rice Research Institute, Key Laboratory of Application and Safety Control of Genetically Modified Crops, Academy of Agricultural Sciences, Southwest University, Chongqing, 400715, China.

Background: In rice, panicle apical abortion is a common phenomenon that usually results in a decreased number of branches and grains per panicle, and consequently a reduced grain yield. A better understanding of the molecular mechanism of panicle abortion is thus critical for maintaining and increasing rice production.

Results: We reported a new rice mutant panicle apical abortion 3 (paa3), which exhibited severe abortion of spikelet development on the upper part of the branches as well as decreased grain size over the whole panicle. Using mapping-based clone, the PAA3 was characterized as the LOC_ Os04g56160 gene, encoding an H-ATPase. The PAA3 was expressed highly in the stem and panicle, and its protein was localized in the plasma membrane. Our data further showed that PAA3 played an important role in maintaining normal panicle development by participating in the removal of reactive oxygen species (ROS) in rice.

Conclusions: Our studies suggested that PAA3 might function to remove ROS, the accumulation of which leads to programmed cell death, and ultimately panicle apical abortion and decreased seed size in the paa3 panicle.
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http://dx.doi.org/10.1186/s12284-021-00509-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282854PMC
July 2021

A Simple Novel Method to Elevate the Sternum in Thoracoscopic Thymectomy.

Surg Innov 2021 Jul 9:15533506211031183. Epub 2021 Jul 9.

Department of Thoracic Surgery, Shenyang Tenth People's Hospital and Shenyang Chest Hospital, Shenyang, China.

The right-chest thoracoscopic surgery approach has become the preferred operation for the treatment of thymic disease. Due to the limited space in the anterior mediastinum, achieving en bloc resection of the tumor is a common difficulty. Here, we report a simple method to lift the sternum by single hook. This method has a lot of advantages, including providing a wide view of the anterior mediastinum for clear vision and being an easy operation.
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http://dx.doi.org/10.1177/15533506211031183DOI Listing
July 2021

Pyrolysis characteristics and kinetics analysis of oil sludge with CaO additive.

Environ Technol 2021 Jul 22:1-11. Epub 2021 Jul 22.

Dalian Yishunlvse Technology Co., Ltd., Dalian, People's Republic of China.

In the process of exploitation, transportation and refining of high-sulfur crude oil, a large number of oil sludge (OS) with high sulfur content is produced. Pyrolysis has been proved to be an effective method for OS disposal, but for solid waste with high sulfur content, lots of sulfur-containing gases will be released during thermal disposal. The addition of calcium oxide in pyrolysis process is an economical and effective way to capture sulfur-containing gases. In order to understand the pyrolysis process of OS with CaO, a thermogravimetric analyser was used to conduct pyrolysis experiments of OS with different Ca/S molar ratios (0, 1, 2 and 3) at different heating rates (10°C/min, 20°C/min, 30°C/min and 40°C/min). The results showed that with the increase of CaO addition the derivative thermogravimetric curves showed a gentle trend. In addition, new weight loss peaks were occurred at 700-900°C and after 1100°C, which were the decomposition of calcium carbonate and calcium sulfate, respectively. The kinetic parameters were solved by Friedman, FWO, and Starink methods, and the results were similar, with an average activation energies () value of 214 kJ/mol. The change trend of the activation energy was followed by an increase and then a decrease corresponding to the change of energy demand for the reaction. The calculated average values of Δ, Δ and Δ were about 207, 447 and -0.3250 kJ/mol, respectively. When the conversion rate was 0.5, the thermodynamic parameters reached their maximum values.
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http://dx.doi.org/10.1080/09593330.2021.1954095DOI Listing
July 2021

Cyberbullying Involvement, Resilient Coping, and Loneliness of Adolescents During Covid-19 in Rural China.

Front Psychol 2021 16;12:664612. Epub 2021 Jun 16.

School of Government, Central University of Finance and Economics, Beijing, China.

Cyberbullying involvement can lead to internal health issues, especially mental health problems. Different coping strategies may reduce or enhance the strengths between cyberbullying experience and mental health problems. In this study, we examined the correlations between cyberbullying involvement and loneliness among a group of children and adolescents during the Covid-19 pandemic in China, focusing on investigating the protecting effect of the resilient coping strategy. The results demonstrated that 86.68% of the students were not involved in cyberbullying activities, 8.19% were victims only, 1.89% was perpetrators only, and 3.24% were both victims and perpetrators. Compared with the non-involved, the victims-only group had a significantly higher degree of reported loneliness and a lower score of resilient coping, while the differences of the other groups were not significant. Resilient coping strategy can significantly reduce loneliness and play a mediating role between cyberbullying victimization and loneliness, but such mitigating effect was relatively weak. Besides, peer relations were the primary protective factors, and age was the primary risk factor of loneliness among the controlled variables. This study can enrich current knowledge of cyberbullying involvement and the psychological health among children and adolescents, especially in the context of the pandemic.
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http://dx.doi.org/10.3389/fpsyg.2021.664612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242172PMC
June 2021

Sesamolin Protects Mice From Ovariectomized Bone Loss by Inhibiting Osteoclastogenesis and RANKL-Mediated NF-κB and MAPK Signaling Pathways.

Front Pharmacol 2021 14;12:664697. Epub 2021 Jun 14.

Guangxi Key Laboratory of Regenerative Medicine, Guangxi-ASEAN Collaborative Innovation Center for Major Disease Prevention and Treatment, Guangxi Medical University, Guangxi, China.

This article was submitted to Experimental Pharmacology and Drug Discovery, a section of the journal Frontiers in Pharmacology. Postmenopausal osteoporosis (PMOP), which increases the risk of fracture, is the most common bone disease in women. PMOP not only increases the risk of death but also imposes a financial burden on countless families. At present, most of the drugs used to treat osteoporosis have significant side effects, so it is important to find effective anti-osteoporosis medications without major side effects. Sesamolin (Ses) is a kind of natural lignan extracted from sesame oil. Many researches have shown that Ses has anti-inflammatory, antioxidative, and anticancer effects, however it is still unknown whether it has any effect on osteoporosis. In this research, we explored the therapeutic effect of Ses in the process of osteoclast formation and bone resorption and found that Ses effectively inhibited osteoclast formation through TRAcP staining and hydroxyapatite resorption assays. Through Western blot analysis of the NF-κB pathway, MAPK pathway, c-Fos and NFATc1, it was found that Ses not only effectively inhibited the activation of NF-κB and MAPK signaling pathways induced by RANKL but also significantly reduced the protein expression of c-Fos and NFATc1. Several genes specifically expressed in osteoclasts were determined by qPCR, and Ses was also found to play a significant inhibitory role on the expression of these genes. Besides, an osteoporosis model induced in ovariectomized (OVX) mice was employed to verify that Ses could effectively reduce bone loss caused by estrogen deficiency . In conclusion, Ses showed promise as a new treatment for postmenopausal osteoporosis.
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http://dx.doi.org/10.3389/fphar.2021.664697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237092PMC
June 2021

Accurate instance segmentation of surgical instruments in robotic surgery: model refinement and cross-dataset evaluation.

Int J Comput Assist Radiol Surg 2021 Sep 25;16(9):1607-1614. Epub 2021 Jun 25.

Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, China.

Purpose: Automatic segmentation of surgical instruments in robot-assisted minimally invasive surgery plays a fundamental role in improving context awareness. In this work, we present an instance segmentation model based on refined Mask R-CNN for accurately segmenting the instruments as well as identifying their types.

Methods: We re-formulate the instrument segmentation task as an instance segmentation task. Then we optimize the Mask R-CNN with anchor optimization and improved Region Proposal Network for instrument segmentation. Moreover, we perform cross-dataset evaluation with different sampling strategies.

Results: We evaluate our model on a public dataset of the MICCAI 2017 Endoscopic Vision Challenge with two segmentation tasks, and both achieve new state-of-the-art performance. Besides, cross-dataset training improved the performance on both segmentation tasks compared with those tested on the public dataset.

Conclusion: Results demonstrate the effectiveness of the proposed instance segmentation network for surgical instruments segmentation. Cross-dataset evaluation shows our instance segmentation model presents certain cross-dataset generalization capability, and cross-dataset training can significantly improve the segmentation performance. Our empirical study also provides guidance on how to allocate the annotation cost for surgeons while labelling a new dataset in practice.
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http://dx.doi.org/10.1007/s11548-021-02438-6DOI Listing
September 2021

Single-cell RNA-sequencing atlas reveals an MDK-dependent immunosuppressive environment in ErbB pathway-mutated gallbladder cancer.

J Hepatol 2021 Jun 23. Epub 2021 Jun 23.

Department of Gastroenterology Surgery, Songjiang Central Hospital Affiliated to The First People's Hospital of Shanghai Jiao Tong University, Shanghai, 201600, China.

Background & Aims: Our previous genomic whole-exome sequencing (WES) data identified the key ErbB pathway mutations that play an essential role in regulating the malignancy of gallbladder cancer (GBC). Herein, we tested the hypothesis that individual cellular components of the tumor microenvironment (TME) in GBC function differentially to participate in ErbB pathway mutation-dependent tumor progression.

Methods: We engaged single-cell RNA-sequencing to reveal transcriptomic heterogeneity and intercellular crosstalk from 13 human GBCs and adjacent normal tissues. In addition, we performed WES analysis to reveal the genomic variations related to tumor malignancy. A variety of bulk RNA-sequencing, immunohistochemical staining, immunofluorescence staining and functional experiments were employed to study the difference between tissues with or without ErbB pathway mutations.

Results: We identified 16 cell types from a total of 114,927 cells, in which epithelial cells, M2 macrophages, and regulatory T cells were predominant in tumors with ErbB pathway mutations. Furthermore, epithelial cell subtype 1, 2 and 3 were mainly found in adenocarcinoma and subtype 4 was present in adenosquamous carcinoma. The tumors with ErbB pathway mutations harbored larger populations of epithelial cell subtype 1 and 2, and expressed higher levels of secreted midkine (MDK) than tumors without ErbB pathway mutations. Increased MDK resulted in an interaction with its receptor LRP1, which is expressed by tumor-infiltrating macrophages, and promoted immunosuppressive macrophage differentiation. Moreover, the crosstalk between macrophage-secreted CXCL10 and its receptor CXCR3 on regulatory T cells was induced in GBC with ErbB pathway mutations. Elevated MDK was correlated with poor overall survival in patients with GBC.

Conclusions: This study has provided valuable insights into transcriptomic heterogeneity and the global cellular network in the TME, which coordinately functions to promote the progression of GBC with ErbB pathway mutations; thus, unveiling novel cellular and molecular targets for cancer therapy.

Lay Summary: We employed single-cell RNA-sequencing and functional assays to uncover the transcriptomic heterogeneity and intercellular crosstalk present in gallbladder cancer. We found that ErbB pathway mutations reduced anti-cancer immunity and led to cancer development. ErbB pathway mutations resulted in immunosuppressive macrophage differentiation and regulatory T cell activation, explaining the reduced anti-cancer immunity and worse overall survival observed in patients with these mutations.
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http://dx.doi.org/10.1016/j.jhep.2021.06.023DOI Listing
June 2021

Identification of the Viral Determinant of Hypovirulence and Host Range in Sclerotiniaceae of a Genomovirus Reconstructed from the Plant Metagenome.

J Virol 2021 Aug 10;95(17):e0026421. Epub 2021 Aug 10.

Department of Horticulture, Agronomy, and Plant Sciences, South Dakota State Universitygrid.263791.8, Brookings, South Dakota, USA.

Uncharacterized viral genomes that encode circular replication-associated proteins of single-stranded DNA viruses have been discovered by metagenomics/metatranscriptomics approaches. Some of these novel viruses are classified in the newly formed family . Here, we determined the host range of a novel genomovirus, SlaGemV-1, through the transfection of Sclerotinia sclerotiorum with infectious clones. Inoculating with the rescued virions, we further transfected Botrytis cinerea and Monilinia fructicola, two economically important members of the family Sclerotiniaceae, and Fusarium oxysporum. SlaGemV-1 causes hypovirulence in , and . SlaGemV-1 also replicates in Spodoptera frugiperda insect cells but not in Caenorhabditis elegans or plants. By expressing viral genes separately through site-specific integration, the replication protein alone was sufficient to cause debilitation. Our study is the first to demonstrate the reconstruction of a metagenomically discovered genomovirus without known hosts with the potential of inducing hypovirulence, and the infectious clone allows for studying mechanisms of genomovirus-host interactions that are conserved across genera. Little is known about the exact host range of widespread genomoviruses. The genome of soybean leaf-associated gemygorvirus-1 (SlaGemV-1) was originally assembled from a metagenomic/metatranscriptomic study without known hosts. Here, we rescued SlaGemV-1 and found that it could infect three important plant-pathogenic fungi and fall armyworm ( Sf9) insect cells but not a model nematode, C. elegans, or model plant species. Most importantly, SlaGemV-1 shows promise for inducing hypovirulence of the tested fungal species in the family Sclerotiniaceae, including Sclerotinia sclerotiorum, , and . The viral determinant of hypovirulence was further identified as replication initiation protein. As a proof of concept, we demonstrate that viromes discovered in plant metagenomes can be a valuable genetic resource when novel viruses are rescued and characterized for their host range.
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http://dx.doi.org/10.1128/JVI.00264-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8354332PMC
August 2021

Metabolomic profiling of single enlarged lysosomes.

Nat Methods 2021 07 14;18(7):788-798. Epub 2021 Jun 14.

Institute on Aging and Brain Disorders, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, China.

Lysosomes are critical for cellular metabolism and are heterogeneously involved in various cellular processes. The ability to measure lysosomal metabolic heterogeneity is essential for understanding their physiological roles. We therefore built a single-lysosome mass spectrometry (SLMS) platform integrating lysosomal patch-clamp recording and induced nano-electrospray ionization (nanoESI)/mass spectrometry (MS) that enables concurrent metabolic and electrophysiological profiling of individual enlarged lysosomes. The accuracy and reliability of this technique were validated by supporting previous findings, such as the transportability of lysosomal cationic amino acids transporters such as PQLC2 and the lysosomal trapping of lysosomotropic, hydrophobic weak base drugs such as lidocaine. We derived metabolites from single lysosomes in various cell types and classified lysosomes into five major subpopulations based on their chemical and biological divergence. Senescence and carcinoma altered metabolic profiles of lysosomes in a type-specific manner. Thus, SLMS can open more avenues for investigating heterogeneous lysosomal metabolic changes during physiological and pathological processes.
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http://dx.doi.org/10.1038/s41592-021-01182-8DOI Listing
July 2021

Polyamine-Responsive Morphological Transformation of a Supramolecular Peptide for Specific Drug Accumulation and Retention in Cancer Cells.

Small 2021 Jun 10:e2101139. Epub 2021 Jun 10.

State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau SAR, 999078, China.

The precise accumulation and extended retention of nanomedicines in the tumor tissue has been highly desired for cancer therapy. Here a novel supramolecular-peptide derived nanodrug (SPN) that can be transformed to microfibers in response to intracellular polyamine in cancer cells for significantly enhanced tumor specific accumulation and retention is developed. The supramolecular-peptide is constructed via the non-covalent interactions between cucurbit[7]uril (CB[7]) and Phe on Phe-Phe-Val-Leu-Lys-camptothecin conjugates (FFVLK-CPT, PC). The resultant amphiphilic supramolecular complex subsequently self-assembles into nanoparticles with a hydrodynamic diameter of 164.2 ± 3.7 nm. Upon internalization into spermine-overexpressed cancer cells, the CB[7]-Phe host-guest pairs can be competitively dissociated by spermine and can release free PC, which immediately form β-sheet structures and subsequently reorganize into microfibers, leading to dramatically improved accumulation, retention, and sustained release of CPT in tumor cells for highly effective cancer therapy. Accordingly, this SPN exhibit rather low toxicity against non-cancerous cells due to the morphological stability and fast exocytosis of the nanodrugs in those cells without abundant spermine. This study reports the first supramolecular peptide capable of polyamine-responsive "nanoparticle-to-microfiber" transformation for specific tumor therapy with minimal side effects. This work also offers novel insights to the design and development of stimuli-responsive nanomaterials as precision medicine.
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http://dx.doi.org/10.1002/smll.202101139DOI Listing
June 2021

Place Attachment and Household Disaster Preparedness: Examining the Mediation Role of Self-Efficacy.

Int J Environ Res Public Health 2021 05 23;18(11). Epub 2021 May 23.

School of Political Science and Public Administration, Shandong University, Qingdao 266237, China.

Household preparedness is essential for resilience-building and disaster risk reduction. Limited studies have explored the correlations between place attachment, self-efficacy, and disaster preparedness, especially in the east Asian cultural context. This study investigates the mediating role of self-efficacy between place attachment and disaster preparedness based on data from the 2018 Shandong General Social Survey (N = 2181) in China. We categorized the preparedness behaviors into three specific clusters: material, behavioral and awareness preparedness. Multiple linear regressions and the Sobel Goodman tests were employed to estimate the correlations with the control of necessary confounding variables such as disaster experience, socioeconomic and demographic characteristics. The results demonstrate that both the place attachment and self-efficacy are correlated with higher degrees of overall preparedness and all three types of preparedness, and self-efficacy plays a mediating role between place attachment and disaster preparedness. These findings highlight the importance of promoting place attachment and self-efficacy in the advocacies and outreach activities of disaster preparedness.
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http://dx.doi.org/10.3390/ijerph18115565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8197108PMC
May 2021

Identification and analysis of urban functional area in Hangzhou based on OSM and POI data.

PLoS One 2021 27;16(5):e0251988. Epub 2021 May 27.

School of Architecture and Urban Planning, Nanjing University, Nanjing, China.

The accurate identification of urban functional areas is of great significance for optimizing urban spatial structure, rationally allocating spatial elements, and promoting the sustainable development of the city. This paper proposes a method to precisely identify urban functional areas by coupling Open Street Map (OSM) and Point of Interest (POI) data. It takes the central urban area of Hangzhou as a case study to analyze the spatial distribution characteristics of the functional areas. The results show that: (1) The central urban areas of Hangzhou are divided into 21 functional areas (6 single functional areas, 14 mixed functional areas and 1 comprehensive functional area). (2) The single functional areas and the mixed functional areas show the geographical distribution characteristics of the looping stratification, which means "Core-periphery" differentiation is obvious, and the comprehensive functional area is relatively scattered. (3) The mixed degree of regional function with ecological function and production function is low while comprehensive functional areas are usually associated with higher potential and vitality. (4) The identification results are in great agreement with the actual situation of Hangzhou central urban area, and the method is feasible. Therefore, this paper can provide a reference for urban development planning and management.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251988PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159005PMC
May 2021

Regional Gas Exchange Measured by Xe Magnetic Resonance Imaging Before and After Combination Bronchodilators Treatment in Chronic Obstructive Pulmonary Disease.

J Magn Reson Imaging 2021 09 7;54(3):964-974. Epub 2021 May 7.

Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.

Background: Hyperpolarized Xe magnetic resonance imaging (MRI) provides a non-invasive assessment of regional pulmonary gas exchange function. This technique has demonstrated that chronic obstructive pulmonary disease (COPD) patients exhibit ventilation defects, reduced interstitial barrier tissue uptake, and poor transfer to capillary red blood cells (RBCs). However, the behavior of these measurements following therapeutic intervention is unknown.

Purpose: To characterize changes in Xe gas transfer function following administration of an inhaled long-acting beta-agonist/long-acting muscarinic receptor antagonist (LABA/LAMA) bronchodilator.

Study Type: Prospective.

Population: Seventeen COPD subjects (GOLD II/III classification per Global Initiative for Chronic Obstructive Lung Disease criteria) were imaged before and after 2 weeks of LABA/LAMA therapy.

Field Strength/sequences: Dedicated ventilation imaging used a multi-slice 2D gradient echo sequence. Three-dimensional images of ventilation, barrier uptake, and RBC transfer used an interleaved, radial, 1-point Dixon sequence. Imaging was acquired at 3 T.

Assessment: Xe measurements were quantified before and after LABA/LAMA treatment by ventilation defect + low percent (ven ) and by barrier uptake and RBC transfer relative to a healthy reference population (bar and RBC ). Pulmonary function tests, including diffusing capacity of the lung for carbon monoxide (DL ), were also performed before and after treatment.

Statistical Tests: Paired t-test, Pearson correlation coefficient (r).

Results: Baseline ven was 57.8 ± 8.4%, bar was 73.2 ± 19.6%, and RBC was 36.5 ± 13.6%. Following treatment, ven decreased to 52.5 ± 10.6% (P < 0.05), and improved in 14/17 (82.4%) of subjects. However, RBC decreased in 10/17 (58.8%) of subjects. Baseline measurements of bar and DL were correlated with the degree of post-treatment change in ven (r = -0.49, P < 0.05 and r = -0.52, P < 0.05, respectively).

Conclusion: LABA/LAMA therapy tended to preferentially improve ventilation in subjects whose Xe barrier uptake and DL were relatively preserved. However, newly ventilated regions often revealed RBC transfer defects, an aspect of lung function opaque to spirometry. These microvasculature abnormalities must be accounted for when assessing the effects of LABA/LAMA therapy.

Level Of Evidence: 1 TECHNICAL EFFICACY STAGE: 4.
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http://dx.doi.org/10.1002/jmri.27662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8363573PMC
September 2021

Beyond Color: The New Carbon Ink.

Adv Mater 2021 May 2:e2005890. Epub 2021 May 2.

Department of Chemistry and Biochemistry, University of Maryland, College Park, MD, 20742, USA.

For thousands of years, carbon ink has been used as a black color pigment for writing and painting purposes. However, recent discoveries of nanocarbon materials, including fullerenes, carbon nanotubes, graphene, and their various derivative forms, together with the advances in large-scale synthesis, are enabling a whole new generation of carbon inks that can serve as an intrinsically programmable materials platform for developing advanced functionalities far beyond color. The marriage between these multifunctional nanocarbon inks with modern printing technologies is facilitating and even transforming many applications, including flexible electronics, wearable and implantable sensors, actuators, and autonomous robotics. This review examines recent progress in the reborn field of carbon inks, highlighting their programmability and multifunctionality for applications in flexible electronics and stimuli-responsive devices. Current challenges and opportunities will also be discussed from a materials science perspective towards the advancement of carbon ink for new applications beyond color.
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http://dx.doi.org/10.1002/adma.202005890DOI Listing
May 2021

Study on the Sleep-Improvement Effects of Baroni in and Targeted Screening to Identify Its Active Components and Mechanism.

Foods 2021 Apr 17;10(4). Epub 2021 Apr 17.

College of Food Science, South China Agricultural University, Guangzhou 510642, China.

Baroni (HC) is an edible plant in Asia, and it has been traditionally used for sleep-improvement. However, the bioactive components and mechanism of HC in sleep-improvement are still unclear. In this study, the sleep-improvement effect of HC hydroalcoholic extract was investigated based on a caffeine-induced insomnia model in (), and the ultrahigh-performance liquid chromatography coupled with electrospray ionization quadrupole Orbitrap high-resolution mass spectrometry (UHPLC-ESI-Orbitrap-MS) and network pharmacology strategy were further combined to screen systematically the active constituents and mechanism of HC in sleep-improvement. The results suggested HC effectively regulated the number of nighttime activities and total sleep time of in a dose-dependent manner and positively regulated the sleep bouts and sleep duration of . The target screening suggested that quercetin, luteolin, kaempferol, caffeic acid, and nicotinic acid were the main bioactive components of HC in sleep-improvements. Moreover, the core targets (Akt1, Cat, Ple, and Sod) affected by HC were verified by the expression of the mRNA of . In summary, this study showed that HC could effectively regulate the sleep of and further clarifies the multi-component and multi-target features of HC in sleep-improvement, which provides a new insight for the research and utilization of HC.
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http://dx.doi.org/10.3390/foods10040883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072781PMC
April 2021

Long term crop rotation effect on subsequent soybean yield explained by soil and root-associated microbiomes and soil health indicators.

Sci Rep 2021 04 28;11(1):9200. Epub 2021 Apr 28.

Department of Biology and Microbiology, South Dakota State University, Brookings, SD, 57007, USA.

Crop rotation is an important management tactic that farmers use to manage crop production and reduce pests and diseases. Long-term crop rotations may select groups of microbes that form beneficial or pathogenic associations with the following crops, which could explain observed crop yield differences with different crop sequences. To test this hypothesis, we used two locations each with four long-term (12-14-year), replicated, rotation treatments: continuous corn (CCC), corn/corn/soybean (SCC), corn/soybean (CSC), and soybean/corn (SCS). Afterwards, soybean was planted, and yield and soil health indicators, bulk soil microbiome, and soybean root-associated microbiome were assessed. Soybean yields, as well as soil protein, and POXC as soil health indicators were higher following CCC than in the other three treatments at both locations. A bacterial taxon in family JG30-KF-AS9 was enriched in CCC, whereas Microvirga, Rhodomicrobium, and Micromonosporaceae were enriched in SCS. Several ascomycetes explain lowered yield as soybean pathogens in SCS. Surprisingly, Tumularia, Pyrenochaetopsis and Schizothecium were enriched in soybean roots after CCC, suggesting corn pathogens colonizing soybean roots as nonpathogens. Our finding of associations between soil health indicators related to microbiomes and soybean yield has wide-ranging implications, opening the possibility of manipulating microbiomes to improve crop yield potential.
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http://dx.doi.org/10.1038/s41598-021-88784-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080707PMC
April 2021

Endonuclease increases efficiency of osteoblast isolation from murine calvariae.

Sci Rep 2021 Apr 19;11(1):8502. Epub 2021 Apr 19.

Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.

Bone is a highly dynamic organ that undergoes remodeling equally regulated by osteoblast-mediated bone formation and osteoclast-mediated bone resorption. To clarify the regulation of osteoblastogenesis, primary murine osteoblasts are required for an in vitro study. Primary osteoblasts are isolated from neonatal calvariae through digestion with collagenase. However, the number of cells collected from one pup is not sufficient for further in vitro experiments, leading to an increase in the use of euthanized pups. We hypothesized that the viscosity of digested calvariae and digestion solution supplemented with collagenase results in cell clumping and reduction of isolated cells from bones. We simply added Benzonase, a genetically engineered endonuclease that shears all forms of DNAs/RNAs, in order to reduce nucleic acid-mediated viscosity. We found that addition of Benzonase increased the number of collected osteoblasts by three fold compared to that without Benzonase through reduction of viscosity. Additionally, Benzonase has no effect on cellular identity and function. The new osteoblast isolation protocol with Benzonase minimizes the number of neonatal pups required for an in vitro study and expands the concept that isolation of other populations of cells including osteocytes that are difficult to be purified could be modified by Benzonase.
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http://dx.doi.org/10.1038/s41598-021-87716-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055883PMC
April 2021

SIRT3 inhibits gallbladder cancer by induction of AKT-dependent ferroptosis and blockade of epithelial-mesenchymal transition.

Cancer Lett 2021 Jul 16;510:93-104. Epub 2021 Apr 16.

Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, 200127, China; Shanghai Key Laboratory of Biliary Tract Disease Research, Shanghai, 200092, China; State Key Laboratory of Oncogenes and Related Genes, Shanghai, 200127, China; Shanghai Research Center of Biliary Tract Disease, Shanghai, 200092, China. Electronic address:

Dysfunction of Sirtuin 3 (SIRT3), an NAD-dependent histone deacetylase, impairs varied mitochondrial metabolic pathways in human cancer. Here, we explored suppressive activity of SIRT3 in the progression of gallbladder cancer (GBC). Expression levels of SIRT3 in patients with GBC were lower than those in the adjacent normal tissue. In addition, decreased expression of SIRT3 in these patients was correlated with poor overall survival. Knockdown of SIRT3 gene in GBC cell lines induced mitochondrial respiration and energy metabolism, but inhibited oxidative ROS. Silence of SIRT3 gene also suppressed AKT-dependent ferroptosis, an iron-dependent and lipid peroxide-mediated cell death. Blockade of AKT activity in sh-SIRT3 cells induced ACSL4 expression that drives ferroptosis, and inhibited epithelial-mesenchymal (EMT) markers and invasive activity. In contrast, overexpression of SIRT3 led to the opposite effects on mitochondrial metabolism and EMT. Finally, transplantation of sh-SIRT3 cells in nude mice resulted in rapid tumor growth and larger tumors that expressed lower E-cadherin and lipid peroxide 4-hydroxynonenal (4-HNE) than those observed in control tumors. Collectively, our studies indicate that SIRT3 functions to inhibit AKT-dependent mitochondrial metabolism and EMT, leading to ferroptosis and tumor suppression.
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http://dx.doi.org/10.1016/j.canlet.2021.04.007DOI Listing
July 2021

Inhibiting ATP6V0D2 Aggravates Liver Ischemia-Reperfusion Injury by Promoting NLRP3 Activation via Impairing Autophagic Flux Independent of Notch1/Hes1.

J Immunol Res 2021 29;2021:6670495. Epub 2021 Mar 29.

Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

At present, liver ischemia-reperfusion (IR) injury is still a great challenge for clinical liver partial resection and liver transplantation. The innate immunity regulated by liver macrophages orchestrates the cascade of IR inflammation and acts as a bridge. As a specific macrophage subunit of vacuolar ATPase, ATP6V0D2 (V-ATPase D2 subunit) has been shown to promote the formation of autophagolysosome in vitro. Our research fills a gap which has existed in the study of inflammatory stress about the V-ATPase subunit ATP6V0D2 in liver macrophages. We first found that the expression of specific ATP6V0D2 in liver macrophages was upregulated with the induction of inflammatory cascade after liver IR surgery, and knockdown of ATP6V0D2 resulted in increased secretion of proinflammatory factors and chemokines, which enhanced activation of NLRP3 and aggravation of liver injury. Further studies found that the exacerbated activation of NLRP3 was related to the autophagic flux regulated by ATP6V0D2. Knocking down ATP6V0D2 impaired the formation of autophagolysosome and aggravated liver IR injury through nonspecific V-ATPase activation independent of V-ATPase-Notchl-Hesl signal axis. In general, we illustrated that the expression of ATP6V0D2 in liver macrophages was upregulated after liver IR, and by gradually promoting the formation of autophagolysosomes to increase autophagy flux to limit the activation of liver inflammation, this regulation is independent of the Notch1-Hes1 signal axis.
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http://dx.doi.org/10.1155/2021/6670495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024071PMC
March 2021

Observation of a Near-Threshold Structure in the K^{+} Recoil-Mass Spectra in e^{+}e^{-}→K^{+}(D_{s}^{-}D^{*0}+D_{s}^{*-}D^{0}).

Phys Rev Lett 2021 Mar;126(10):102001

Institute of High Energy Physics, Beijing 100049, People's Republic of China.

We report a study of the processes of e^{+}e^{-}→K^{+}D_{s}^{-}D^{*0} and K^{+}D_{s}^{*-}D^{0} based on e^{+}e^{-} annihilation samples collected with the BESIII detector operating at BEPCII at five center-of-mass energies ranging from 4.628 to 4.698 GeV with a total integrated luminosity of 3.7  fb^{-1}. An excess of events over the known contributions of the conventional charmed mesons is observed near the D_{s}^{-}D^{*0} and D_{s}^{*-}D^{0} mass thresholds in the K^{+} recoil-mass spectrum for events collected at sqrt[s]=4.681  GeV. The structure matches a mass-dependent-width Breit-Wigner line shape, whose pole mass and width are determined as (3982.5_{-2.6}^{+1.8}±2.1)  MeV/c^{2} and (12.8_{-4.4}^{+5.3}±3.0)  MeV, respectively. The first uncertainties are statistical and the second are systematic. The significance of the resonance hypothesis is estimated to be 5.3  σ over the contributions only from the conventional charmed mesons. This is the first candidate for a charged hidden-charm tetraquark with strangeness, decaying into D_{s}^{-}D^{*0} and D_{s}^{*-}D^{0}. However, the properties of the excess need further exploration with more statistics.
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http://dx.doi.org/10.1103/PhysRevLett.126.102001DOI Listing
March 2021
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