Publications by authors named "Hongyu Yu"

117 Publications

Recent Progress on Perovskite Surfaces and Interfaces in Optoelectronic Devices.

Adv Mater 2021 Jun 17:e2006004. Epub 2021 Jun 17.

Dr. D. Luo, Prof. H. Yu, Prof. Z.-H. Lu, School of Microelectronics, Southern University of Science and Technology, Shenzhen, Guangdong, 518055, China.

Surfaces and heterojunction interfaces, where defects and energy levels dictate charge-carrier dynamics in optoelectronic devices, are critical for unlocking the full potential of perovskite semiconductors. In this progress report, chemical structures of perovskite surfaces are discussed and basic physical rules for the band alignment are summarized at various perovskite interfaces. Common perovskite surfaces are typically decorated by various compositional and structural defects such as residual surface reactants, discrete nanoclusters, reactions by products, vacancies, interstitials, antisites, etc. Some of these surface species induce deep-level defect states in the forbidden band forming very harmful charge-carrier traps and affect negatively the interface band alignments for achieving optimal device performance. Herein, an overview of research progresses on surface and interface engineering is provided to minimize deep-level defect states. The reviewed subjects include selection of interface and substrate buffer layers for growing better crystals, materials and processing methods for surface passivation, the surface catalyst for microstructure transformations, organic semiconductors for charge extraction or injection, heterojunctions with wide bandgap perovskites or nanocrystals for mitigating defects, and electrode interlayer for preventing interdiffusion and reactions. These surface and interface engineering strategies are shown to be critical in boosting device performance for both solar cells and light-emitting diodes.
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http://dx.doi.org/10.1002/adma.202006004DOI Listing
June 2021

Design, synthesis, and biological evaluation of novel sulindac derivatives as partial agonists of PPARγ with potential anti-diabetic efficacy.

Eur J Med Chem 2021 May 24;222:113542. Epub 2021 May 24.

School of Pharmaceutical Sciences, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Xiamen, Fujian, 361102, China; High Throughput Drug Screening Platform, Xiamen University, Xiamen, Fujian, 361102, China. Electronic address:

Peroxisome proliferator-activated receptor gamma (PPARγ) is a valuable drug target for diabetic treatment and ligands of PPARγ have shown potent anti-diabetic efficacy. However, to overcome the severe side effects of current PPARγ-targeted drugs, novel PPARγ ligands need to be developed. Sulindac, an identified ligand of PPARγ, is widely used in clinic as a non-steroidal anti-inflammatory drug. To explore its potential application for diabetes, we designed and synthesized a series of sulindac derivatives to investigate their structure-activity relationship as PPARγ ligand and potential anti-diabetic effect. We found that meta-substitution in sulindac's benzylidene moiety was beneficial to PPARγ binding and transactivation. Z rather than E configuration of the benzylidene double bond endowed derivatives with the selectivity of PPARγ activation. The indene fluorine is essential for binding and regulating PPARγ. Compared with rosiglitazone, compound 6b with benzyloxyl meta-substitution and Z benzylidene double bond weakly induced adipogenesis and PPARγ-targeted gene expression. However, 6b potently improved glucose tolerance in a diabetic mice model. Unlike rosiglitazone, 6b was devoid of apparent toxicity to osteoblastic formation. Thus, we provided some useful guidelines for PPARγ-based optimization of sulindac and an anti-diabetic lead compound with less side effects.
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http://dx.doi.org/10.1016/j.ejmech.2021.113542DOI Listing
May 2021

Dielectric screening in perovskite photovoltaics.

Nat Commun 2021 Apr 30;12(1):2479. Epub 2021 Apr 30.

State Key Laboratory for Artificial Microstructure and Mesoscopic Physics, School of Physics, Frontiers Science Center for Nano-optoelectronics & Collaborative Innovation Center of Quantum Matter, Peking University, Beijing, China.

The performance of perovskite photovoltaics is fundamentally impeded by the presence of undesirable defects that contribute to non-radiative losses within the devices. Although mitigating these losses has been extensively reported by numerous passivation strategies, a detailed understanding of loss origins within the devices remains elusive. Here, we demonstrate that the defect capturing probability estimated by the capture cross-section is decreased by varying the dielectric response, producing the dielectric screening effect in the perovskite. The resulting perovskites also show reduced surface recombination and a weaker electron-phonon coupling. All of these boost the power conversion efficiency to 22.3% for an inverted perovskite photovoltaic device with a high open-circuit voltage of 1.25 V and a low voltage deficit of 0.37 V (a bandgap ~1.62 eV). Our results provide not only an in-depth understanding of the carrier capture processes in perovskites, but also a promising pathway for realizing highly efficient devices via dielectric regulation.
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http://dx.doi.org/10.1038/s41467-021-22783-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087789PMC
April 2021

Long Noncoding RNAs in Myocardial Ischemia-Reperfusion Injury.

Oxid Med Cell Longev 2021 5;2021:8889123. Epub 2021 Apr 5.

Department of Cardiology, The Second Hospital of Jilin University, 218 Ziqiang Road, Changchun, China 130041.

Following an acute myocardial infarction, reperfusion therapy is currently the most effective way to save the ischemic myocardium; however, restoring blood flow may lead to a myocardial ischemia-reperfusion injury (MIRI). Recent studies have confirmed that long-chain noncoding RNAs (LncRNAs) play important roles in the pathophysiology of MIRIs. These LncRNA-mediated roles include cardiomyocyte apoptosis, autophagy, necrosis, oxidative stress, inflammation, mitochondrial dysfunction, and calcium overload, which are regulated through the expression of target genes. Thus, LncRNAs may be used as clinical diagnostic markers and therapeutic targets to treat or prevent MIRI. This review evaluates the research on LncRNAs involved in MIRIs and provides new ideas for preventing and treating this type of injury.
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http://dx.doi.org/10.1155/2021/8889123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041529PMC
May 2021

High-temperature superconductivity in transition metallic hydrides MH (M = Mo, W, Nb, and Ta) under high pressure.

Phys Chem Chem Phys 2021 Mar 12;23(11):6717-6724. Epub 2021 Mar 12.

State Key Laboratory of Superhard Materials, Department of Physics, Jilin University, Changchun 130012, People's Republic of China.

The discovery of HS and LaH is an important step towards the development of room temperature superconductors which fuels the enthusiasm for finding promising superconductors among hydrides at high pressure. In the present study, three new and stable stoichiometric MoH, MoH and MoH compounds were found in the pressure range of 100-300 GPa. The highly hydrogen-rich phase of Cmmm-MoH has a layered structure that contains various forms of hydrogen: H, H and H units. It is a high-T material with an estimated T value in the range of 165-182 K at 250 GPa. The same structures are also found in NbH, TaH, and WH, each material showing T ranging from 117 to 168 K. By combining the method of using two coupling constants λ and λ, and two characteristic frequencies (optical and acoustic) with first-principle calculations, we found that the high values of T are mainly caused by the presence of high frequency optical modes, but the acoustic modes also play a noticeable role.
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http://dx.doi.org/10.1039/d0cp06435aDOI Listing
March 2021

Spin Hamiltonians in Magnets: Theories and Computations.

Molecules 2021 Feb 4;26(4). Epub 2021 Feb 4.

Key Laboratory of Computational Physical Sciences (Ministry of Education), State Key Laboratory of Surface Physics, Department of Physics, Fudan University, Shanghai 200433, China.

The effective spin Hamiltonian method has drawn considerable attention for its power to explain and predict magnetic properties in various intriguing materials. In this review, we summarize different types of interactions between spins (hereafter, spin interactions, for short) that may be used in effective spin Hamiltonians as well as the various methods of computing the interaction parameters. A detailed discussion about the merits and possible pitfalls of each technique of computing interaction parameters is provided.
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http://dx.doi.org/10.3390/molecules26040803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913993PMC
February 2021

Detection of microRNA-33a-5p in serum, urine and renal tissue of patients with IgA nephropathy.

Exp Ther Med 2021 Mar 11;21(3):205. Epub 2021 Jan 11.

Department of Nephrology, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.

The present study aimed to detect the levels of microRNA (miR)-33a-5p in the renal tissue, serum and urine of patients with primary IgA nephropathy (IgAN), thereby preliminarily exploring the association between the levels of miR-33a-5p and the condition of primary IgAN to provide evidence for the expression of miR-33a-5p in the serum and urine of IgAN patients as a clinical marker. Reverse-transcription quantitative PCR was performed to evaluate the level of miR-33a-5p in IgAN patients according to severity and pathological classification. The results suggested that the levels of miR-33a-5p in the serum, urine and kidney tissues of patients with IgAN were lower than those of the control tissues obtained from cancer patients (0.28±0.25 vs. 1.00±0.45, P<0.05; 0.34±0.28 vs. 1.00±0.53, P<0.05; 0.47±0.27 vs. 1.00±0.38, P<0.05, respectively). Receiver operating characteristic curve analysis suggested that the serum and urine levels of miR-33a-5p may be used as a marker to differentiate renal injury in IgAN patients from healthy individuals. At the same time, according to the estimated glomerular filtration rate (eGFR) and Lee classification of nephropathy, it was determined that with the progression of renal failure and the increase of the pathological grade of kidney tissue, the relative level of miR-33a-5p in kidney tissue also decreased (eGFR <50 ml/min vs. eGFR ≥50 ml/min/1.73 m group: 0.38±0.27 vs. 1.00±0.34, P<0.001; Lee grade ≤3 group vs. Lee grade >3: 1.00±0.48 vs. 0.38±0.45, P<0.05). This result suggested that the levels of miR-33a-5p in serum, urine and kidney tissues decreased with the severity of renal injury and the progression of renal failure in patients with IgAN. Hence, miR-33a-5p detected in the serum and urine may be used as a non-invasive biomarker to reflect the progression of renal injury and renal failure in patients with IgAN.
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http://dx.doi.org/10.3892/etm.2021.9638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818539PMC
March 2021

MiR-34c promotes hepatic stellate cell activation and Liver Fibrogenesis by suppressing ACSL1 expression.

Int J Med Sci 2021 1;18(3):615-625. Epub 2021 Jan 1.

Department of Pathology, Changzheng Hospital, Navy Medical University (Second Military Medical University), Shanghai 200003, China.

Normally, there are multiple microRNAs involved in the pathogenesis of liver fibrosis. In our work, we aimed at identifying the role of miR-34c in the hepatic stellate cell (HSC) activation and liver fibrosis and its potential mechanism. Our results have shown that during natural activation of HSC, the level of miR-34c was increased significantly whereas acyl-CoA synthetase long-chain family member-1(ACSL1), which is a key enzyme can affect fatty acid(FA) synthesis, was decreased. A double fluorescence reporter assay further confirmed that ACSL1 is a direct target gene of miR-34c. Moreover, the inhibition of miR-34C can attenuate the synthesis of collagen in HSC-T6. In our rescue assay, ACSL1 expression was 1.49-fold higher compared to normal control cells which were transfected with the miR-34c inhibitor in a stable low expression ACSL1 cell line. While at the same time, α-SMA and Col1α expression decreased by 18.22% and 2.58%, respectively. Moreover, we performed an model using dimethylnitrosamine (DMN) in conjunction with the miR-34c agomir, combined with the treatment of DMN and the miR-34c agomir can increase liver fibrosis. Meanwhile, the degree of hepatic fibrosis was increased and lipid droplets reduced dramatically in rats and HSC-T6 cell treated with miR-34c mimics alone compared to untreated groups. Our results indicate that miR-34c plays an essential role in liver fibrosis by targeting ACSL1 closely associated with lipid droplets, and it might be used as a potential therapeutic target.
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http://dx.doi.org/10.7150/ijms.51589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797556PMC
January 2021

Buried Interfaces in Halide Perovskite Photovoltaics.

Adv Mater 2021 Feb 4;33(7):e2006435. Epub 2021 Jan 4.

State Key Laboratory for Artificial Microstructure and Mesoscopic Physics, School of Physics, Frontiers Science Center for Nano-optoelectronics, and Collaborative Innovation Center of Quantum Matter, Peking University, Beijing, 100871, China.

Understanding the fundamental properties of buried interfaces in perovskite photovoltaics is of paramount importance to the enhancement of device efficiency and stability. Nevertheless, accessing buried interfaces poses a sizeable challenge because of their non-exposed feature. Herein, the mystery of the buried interface in full device stacks is deciphered by combining advanced in situ spectroscopy techniques with a facile lift-off strategy. By establishing the microstructure-property relations, the basic losses at the contact interfaces are systematically presented, and it is found that the buried interface losses induced by both the sub-microscale extended imperfections and lead-halide inhomogeneities are major roadblocks toward improvement of device performance. The losses can be considerably mitigated by the use of a passivation-molecule-assisted microstructural reconstruction, which unlocks the full potential for improving device performance. The findings open a new avenue to understanding performance losses and thus the design of new passivation strategies to remove imperfections at the top surfaces and buried interfaces of perovskite photovoltaics, resulting in substantial enhancement in device performance.
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http://dx.doi.org/10.1002/adma.202006435DOI Listing
February 2021

Myeloid-Derived Suppressor Cells Promote the Progression of Primary Membranous Nephropathy by Enhancing Th17 Response.

Front Immunol 2020 20;11:1777. Epub 2020 Aug 20.

Central Laboratory, The First Hospital of Jilin University, Changchun, China.

Several studies have confirmed that the myeloid-derived suppressor cells (MDSCs) are closely associated with autoimmune diseases, but their exact role in these processes remains largely unclear. Here, we investigated the role MDSCs in patients with primary membranous nephropathy (PMN). Compared to healthy controls (HCs), PMN patients showed significantly increased number of HLA-DRCD11bCD33 MDSCs in the peripheral blood, including both CD14CD66b monocytic and CD14CD66b granulocytic MDSCs. The frequency of MDSCs was positively correlated with the level of serum anti-phospholipase A2 receptor (anti-PLA2R), 24-h urine protein quantification, and disease activity in PMN patients. Consistently, enhanced T helper 2 (Th2) and T helper 17 (Th17) immune responses were positively associated with plasma anti-PLA2R levels, 24-h urine protein quantification, and the disease activity in PMN patients. Moreover, compared to HCs, MDSCs from PMN patients exhibited significantly elevated arginase-1 (ARG-1) production and increased potential to promote Th17 differentiation in an ARG-1-dependent manner. This study directly demonstrates a pathogenic role for MDSCs in human PMN and provides a molecular mechanism for the pathogenesis of PMN. Our data show that MDSCs may promote PMN disease progression mainly by enhancing Th17 response. Therefore, MDSCs may be an important diagnostic, therapeutic, and prognostic marker for PMN diseases.
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http://dx.doi.org/10.3389/fimmu.2020.01777DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468481PMC
April 2021

Apatinib in patients with advanced chordoma: a single-arm, single-centre, phase 2 study.

Lancet Oncol 2020 09;21(9):1244-1252

Department of Orthopedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai, China. Electronic address:

Background: No standard treatment exists for advanced chordoma. Apatinib has been found to have promising efficacy and manageable adverse effects for the treatment of solid tumours. We aimed to investigate the safety and antitumour activity of apatinib in patients with advanced chordoma.

Methods: We did a single-arm, phase 2 study at one tertiary hospital in Shanghai, China. Eligible patients were aged 18-75 years, with histologically confirmed advanced chordoma that was unresectable or resectable only through demolitive surgery, who had previously received surgical treatment, with at least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, evidence of tumour progression on enhanced CT or MRI in the previous 6 months, and an Eastern Cooperative Oncology Group performance status of 0-2. Patients received oral 500 mg apatinib once daily until disease progression or unacceptable toxicity. The co-primary endpoints were progression-free survival and objective response rate according to RECIST 1.1 and Choi criteria by investigator assessment. Progression-free survival was assessed in the intention-to-treat population. Objective response rate was assessed in the per-protocol population, which included all enrolled patients who were compliant with the protocol and had at least one post-baseline assessment. Safety was analysed in all patients with complete safety data. This study is ongoing, but recruitment is complete. This study is registered with Chictr.org.cn, ChiCTR-OIC-17013586.

Findings: Between Aug 21, 2017, and May 31, 2019, we screened 32 patients, of whom 30 were enrolled. Median follow-up was 14·2 months (IQR 9·4-19·7). Of the 27 patients included in the per-protocol population, one patient (3·7%; 95% CI 0-11·3) achieved an objective response according to RECIST, and seven patients (25·9%; 8·3-43·6) achieved an objective response according to Choi criteria. Median progression-free survival was 18 months (95% CI 3-34) according to RECIST and 18 months (3-33) according to Choi criteria. The most common treatment-related grade 3 adverse events were hypertension (seven [24%] of 29 patients) and proteinuria (two [7%]). No treatment-related grade 4 adverse events or treatment-related deaths were observed.

Interpretation: To our knowledge, this is the first trial of apatinib for the treatment of advanced chordoma. Apatinib shows promising activity and manageable toxicity and thus might be an option for the treatment of advanced chordoma.

Funding: None.
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http://dx.doi.org/10.1016/S1470-2045(20)30466-6DOI Listing
September 2020

Novel visualized quantitative epigenetic imprinted gene biomarkers diagnose the malignancy of ten cancer types.

Clin Epigenetics 2020 05 24;12(1):71. Epub 2020 May 24.

Department of Pulmonary Medicine, Shanghai Respiratory Research Institute, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.

Background: Epigenetic alterations are involved in most cancers, but its application in cancer diagnosis is still limited. More practical and intuitive methods to detect the aberrant expressions from clinical samples using highly sensitive biomarkers are needed. In this study, we developed a novel approach in identifying, visualizing, and quantifying the biallelic and multiallelic expressions of an imprinted gene panel associated with cancer status. We evaluated the normal and aberrant expressions measured using the imprinted gene panel to formulate diagnostic models which could accurately distinguish the imprinting differences of normal and benign cases from cancerous tissues for each of the ten cancer types.

Results: The Quantitative Chromogenic Imprinted Gene In Situ Hybridization (QCIGISH) method developed from a 1013-case study which provides a visual and quantitative analysis of non-coding RNA allelic expressions identified the guanine nucleotide-binding protein, alpha-stimulating complex locus (GNAS), growth factor receptor-bound protein (GRB10), and small nuclear ribonucleoprotein polypeptide N (SNRPN) out of five tested imprinted genes as efficient epigenetic biomarkers for the early-stage detection of ten cancer types. A binary algorithm developed for cancer diagnosis showed that elevated biallelic expression (BAE), multiallelic expression (MAE), and total expression (TE) measurements for the imprinted gene panel were associated with cell carcinogenesis, with the formulated diagnostic models achieving consistently high sensitivities (91-98%) and specificities (86-98%) across the different cancer types.

Conclusions: The QCIGISH method provides an innovative way to visually assess and quantitatively analyze individual cells for cancer potential extending from hyperplasia and dysplasia until carcinoma in situ and invasion, which effectively supplements standard clinical cytologic and histopathologic diagnosis for early cancer detection. In addition, the diagnostic models developed from the BAE, MAE, and TE measurements of the imprinted gene panel GNAS, GRB10, and SNRPN could provide important predictive information which are useful in early-stage cancer detection and personalized cancer management.
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http://dx.doi.org/10.1186/s13148-020-00861-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7245932PMC
May 2020

Dual-Mode Hybrid Quasi-SAW/BAW Resonators With High Effective Coupling Coefficient.

IEEE Trans Ultrason Ferroelectr Freq Control 2020 Sep 6;67(9):1916-1921. Epub 2020 Apr 6.

This article reports on a design journey for ScAl - N-based dual-mode hybrid quasi-surface and bulk acoustic wave (quasi-SAW/BAW) resonators. Four types of acoustic excitation configurations are proposed in these designs based on Sc AlN/6H-SiC stack architectures. The influence of Sc AlN materials, film thickness, and device configurations on the performance is investigated. After design optimization, the final dual-mode hybrid quasi-SAW/BAW resonators comprise of top electrode, partially etched Sc AlN pillars, and bottom electrode, which are stacked on a 6H-SiC substrate. The coupled quasi-SAW and BAW excited in the hybrid resonators enhance the resonance for both quasi-Rayleigh and quasi-Sezawa modes which results in a high effective coupling coefficient (K) and phase velocity ( v ). Simulation results show that the optimized hybrid quasi-SAW/BAW resonator based on Mo/Sc AlN/Mo/6H-SiC configuration with SiO filling the grooves has a remarkable K value of 14.55% and a high v above 7500 m/s, which make this kind of dual-mode hybrid quasi-SAW/BAW resonators have great potential in wideband and high-frequency applications.
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http://dx.doi.org/10.1109/TUFFC.2020.2985983DOI Listing
September 2020

Mechanisms of lncRNA/microRNA interactions in angiogenesis.

Life Sci 2020 Aug 28;254:116900. Epub 2019 Nov 28.

Department of Cardiology, the Second Hospital of Jilin University, 218 Ziqiang Road, Changchun, 130041, China. Electronic address:

Angiogenesis is a complex physiological process. However, over the past couple of decades, abnormally accelerated or pathological angiogenesis has garnered greater attention from researchers the world over. Studies have shown that this abnormal and uncontrolled angiogenesis not only promotes inflammatory responses but also plays a role in various malignant and cardiovascular diseases. These include solid tumors, atherosclerosis, blinding retinopathy, and other diseases. Furthermore, there is mounting evidence that noncoding RNAs, especially lncRNAs and microRNAs, play important roles in the regulation of angiogenesis. In recent years, numerous studies have found that lncRNA may serve as an endogenous sponge to regulate the expression and function of miRNA, which in turn bind to lncRNA, regulating their stability. Therefore, this review focuses on the mechanisms of lncRNA/microRNA interactions in angiogenesis. A better understanding of such lncRNA/microRNA interactions may provide helpful insights and shed new light on areas of research for identifying diagnostic markers and therapeutic approaches for treating angiogenesis-related diseases.
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http://dx.doi.org/10.1016/j.lfs.2019.116900DOI Listing
August 2020

Role of TM-TM Connection Induced by Opposite d-Electron States on the Hardness of Transition-Metal (TM = Cr, W) Mononitrides.

Inorg Chem 2019 Nov 7;58(22):15573-15579. Epub 2019 Nov 7.

State Key Laboratory of Superhard Materials, College of Physics , Jilin University , Changchun 130012 , People's Republic of China.

Recent reports exposed an astonishing factor of high hardness that the connection between transition-metal (TM) atoms could enhance hardness, which is in contrast to the usual understanding that TM-TM will weaken hardness as the source of metallicity. It is surprising that there are two opposite mechanical characteristics in the one TM-TM bond. To uncover the intrinsic reason, we studied two appropriate mononitrides, CrN and WN, with the same light-element (LE) content and valence electron concentration. The two high-quality compounds were synthesized by a new metathesis under high pressure, and the Vickers hardness is 13.0 GPa for CrN and 20.0 GPa for WN. Combined with theoretical calculations, we found that the strong correlation of d electrons in TM-TM could seriously affect hardness. Thus, we make the complementary suggestions of the previous hardness factors that the antibonding d-electron state in TM-TM near the Fermi level should be avoided and a strong d covalent coupling in TM-TM is very beneficial for high hardness. Our results are very important for the further design of high-hardness and multifunctional TM and LE compounds.
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http://dx.doi.org/10.1021/acs.inorgchem.9b02634DOI Listing
November 2019

EWS-FLI1-mediated tenascin-C expression promotes tumour progression by targeting MALAT1 through integrin α5β1-mediated YAP activation in Ewing sarcoma.

Br J Cancer 2019 11 25;121(11):922-933. Epub 2019 Oct 25.

Spinal Tumor Center, Department of Orthopaedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, P. R. China.

Background: The extracellular matrix has been critically associated with the tumorigenesis and progression of Ewing sarcoma (ES). However, the regulatory and prognostic roles of tenascin-C (TNC) in ES remain unclear.

Methods: TNC expression was examined in specimens by immunohistochemistry, and the association of TNC expression with ES patient survival was also analysed. TNC-knockout cell lines were constructed using CRISPR/Cas9 methods. In vitro experiments and in vivo bioluminescent imaging using BALB/c nude mice were conducted to evaluate the effect of TNC on ES tumour progression. RNA sequencing was performed, and the underlying mechanism of TNC was further explored.

Results: TNC was overexpressed in ES tissue and cell lines, and TNC overexpression was associated with poor survival in ES patients. TNC enhanced cell proliferation, migration and angiogenesis in vitro and promoted ES metastasis in vivo. The oncoprotein EWS-FLI1 profoundly increased TNC expression by directly binding to the TNC promoter region. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) upregulation induced by Yes-associated protein (YAP) activation was responsible for TNC-regulated ES tumour progression. Activated integrin α5β1 signalling might be correlated with YAP dephosphorylation and nuclear translocation.

Conclusions: TNC may promote ES tumour progression by targeting MALAT1 through integrin α5β1-mediated YAP activation.
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http://dx.doi.org/10.1038/s41416-019-0608-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889507PMC
November 2019

Ultra-High Sensitive NO Gas Sensor Based on Tunable Polarity Transport in CVD-WS/IGZO p-N Heterojunction.

ACS Appl Mater Interfaces 2019 Oct 16;11(43):40850-40859. Epub 2019 Oct 16.

Department of Microelectronics , Delft University of Technology , Delft 2628 CD , The Netherlands.

In this work, a thin-film transistor gas sensor based on the p-N heterojunction is fabricated by stacking chemical vapor deposition-grown tungsten disulfide (WS) with a sputtered indium-gallium-zinc-oxide (IGZO) film. To the best of our knowledge, the present device has the best NO gas sensor response compared to all the gas sensors based on transition-metal dichalcogenide materials. The gas-sensing response is investigated under different NO concentrations, adopting heterojunction device mode and transistor mode. High sensing response is obtained of p-N diode in the range of 1-300 ppm with values of 230% for 5 ppm and 18 170% for 300 ppm. On the transistor mode, the gas-sensing response can be modulated by the gate bias, and the transistor shows an ultrahigh response after exposure to NO, with sensitivity values of 6820% for 5 ppm and 499 400% for 300 ppm. Interestingly, the transistor has a typical ambipolar behavior under dry air, while the transistor becomes p-type as the amount of NO increases. The assembly of these results demonstrates that the WS/IGZO device is a promising platform for the NO-gas detection, and its gas-modulated transistor properties show a potential application in tunable engineering for two-dimensional material heterojunction-based transistor device.
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http://dx.doi.org/10.1021/acsami.9b13773DOI Listing
October 2019

Disruption of Robo2-Baiap2 integrated signaling drives cystic disease.

JCI Insight 2019 09 19;4(18). Epub 2019 Sep 19.

Department of Nephrology, Chinese PLA General Hospital, Medical School of Chinese PLA, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, China.

Hereditary renal cystic diseases are characterized by defects in primary cilia of renal tubular epithelial cells and abnormality of tubular epithelium, which ultimately result in the development of renal cysts. However, the mechanism leading from abnormality of the tubular epithelium to cystogenesis is not well understood. In this report, we demonstrate a critical role for Robo2 in regulating epithelial development, including ciliogenesis, polarization, and differentiation. We found that Robo2 deficiency results in cystic kidneys, and the cyst cells showed defective cilia and polarity defects in tubular epithelium. The cyst cells, less than terminally differentiated, continue to proliferate. We further established that Robo2 works with p53 as well as polarity and ciliary proteins (Par3, PKCς, ZO-2, and Claudin-2) to regulate these processes. Robo2 binds to Baiap2 (also known as IRSp53) through the IRSp53/MIM homology domain in renal epithelial cells. This binding allows Robo2 to phosphorylate MDM2 at Ser166 via Baiap2 and maintain p53 homeostasis. Disruption of the Robo2-Baiap2 complex causes MDM2 to be subjected to dephosphorylation, leading to a high level of active p53, and initiated p53-mediated cellular senescence via p21 and decreased the expression of ZO-1, ZO-2, PKCς, Par3, and Claudin-2 proteins, resulting in defects in epithelial development, including ciliogenesis, polarization, and differentiation. Importantly, double knockout of Robo2 and p53 rescued all the epithelial defects in kidneys compared with those in Robo2-knockout kidneys. Taken together, the present results demonstrate that Robo2 deficiency causes renal cystic disease, which is largely dependent on defective Robo2-Baiap2 integrated signaling in kidneys.
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http://dx.doi.org/10.1172/jci.insight.127602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6795383PMC
September 2019

Mesangial Cells Exhibit Features of Antigen-Presenting Cells and Activate CD4+ T Cell Responses.

J Immunol Res 2019 17;2019:2121849. Epub 2019 Jun 17.

Department of Nephrology, The Second Hospital of Jilin University, Changchun, Jilin, China.

Background: Mesangial cells play a prominent role in the development of inflammatory diseases and autoimmune disorders of the kidney. Mesangial cells perform the essential functions of helping to ensure that the glomerular structure is stable and regulating capillary flow, and activated mesangial cells acquire proinflammatory activities. We investigated whether activated mesangial cells display immune properties and control the development of T cell immunity.

Methods: Flow cytometry analysis was used to study the expression of antigen-presenting cell surface markers and costimulatory molecules in mesangial cells. CD4+ T cell activation induced by mesangial cells was detected in terms of T cell proliferation and cytokine production.

Results: IFN--treated mesangial cells express membrane proteins involved in antigen presentation and T cell activation, including MHC-II, ICAM-1, CD40, and CD80. This finding suggests that activated mesangial cells can take up and present antigenic peptides to initiate CD4+ T cell responses and thus act as nonprofessional antigen-presenting cells. Polarization of naïve CD4+ T cells (Th0 cells) towards the Th1 phenotype was induced by coculture with activated mesangial cells, and the resulting Th1 cells showed increased mRNA and protein expression of inflammation-associated genes.

Conclusion: Mesangial cells can present antigen and modulate CD4+ T lymphocyte proliferation and differentiation. Interactions between mesangial cells and T cells are essential for sustaining the inflammatory response in a variety of glomerulonephritides. Therefore, mesangial cells might participate in immune function in the kidney.
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http://dx.doi.org/10.1155/2019/2121849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6604415PMC
December 2019

Crosstalk between the lncRNA UCA1 and microRNAs in cancer.

FEBS Lett 2019 08 10;593(15):1901-1914. Epub 2019 Jul 10.

Department of Clinical Laboratory, Second Hospital of Jilin University, Changchun, China.

Long non-coding RNAs (lncRNAs) are a major subset of highly conserved non-coding RNAs (ncRNAs) that consist of at least 200 nucleotides and have limited protein-coding potential. Cumulative data have shown that lncRNAs are deregulated in many types of cancer and may control pathophysiological processes of cancer at various levels, including transcription, post-transcription and translation. Recently, lncRNAs have been demonstrated to interact with microRNAs (miRNAs), another major subset of ncRNAs, which regulate physiological and pathological processes by inhibiting target mRNA translation or promoting mRNA degradation. The lncRNA urothelial carcinoma-associated 1 (UCA1) has recently gained much attention as it is overexpressed in many types of cancer and is involved in carcinogenesis. Here, we review the crosstalk between UCA1 and miRNAs during the pathogenesis of cancer, with a focus on cancer-cell proliferation, invasion, drug resistance, and metabolism.
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http://dx.doi.org/10.1002/1873-3468.13470DOI Listing
August 2019

SAR study of celastrol analogs targeting Nur77-mediated inflammatory pathway.

Eur J Med Chem 2019 Sep 12;177:171-187. Epub 2019 May 12.

School of Pharmaceutical Science, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Fujian, 361002, China; Sanford Burnham Prebys Medical Discovery Institute, 10901 N. Torrey Pines Road, La Jolla, CA, 92037, USA. Electronic address:

Nur77, an orphan member of the nuclear receptor superfamily, plays an important role in the regulation of inflammatory processes. Our previous work found that celastrol, a pentacyclic triterpene, bound to Nur77 to inhibit inflammation in a Nur77-dependent manner. Celastrol binding to Nur77 promotes Nur77 translocation from nucleus to cytoplasm, resulting in clearance of inflamed mitochondria and then alleviation of inflammation. Here, we report the design, synthesis, SAR study and biological evaluation of a series of celastrol analogs. A total of 24 celastrol derivatives were made. Compound 3a with a K of 0.87 μM was found to be less toxic than celastrol and could be a hit molecule for further optimization.
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http://dx.doi.org/10.1016/j.ejmech.2019.05.009DOI Listing
September 2019

Structure and superconductivity of protactinium hydrides under high pressure.

J Phys Condens Matter 2019 Aug 26;31(31):315403. Epub 2019 Apr 26.

State Key Laboratory of Superhard Materials, College of Physics, Jilin University, Changchun 130012, People's Republic of China.

We systematically study the stability, crystal structure, electronic property, and superconductivity of protactinium hydride (PaH ) (n  =  1-9) at a pressure range of 1 atm to 300 GPa by using the first principle of density functional theory. PaH compounds are very rich, featuring six stoichiometries, such as PaH, PaH, PaH, PaH, PaH and PaH. PaH possesses the highly symmetrical crystal structure Fm-3m with cubic H8 units, which is predicted to be thermodynamically stable above 32 GPa. This phase maintains a dynamically stable decompression at 10 GPa. Electron-phonon coupling (EPC) calculations show that Fm-3m-PaH exhibits high superconducting critical transition temperature (T ) value of 79 K at 10 GPa due to a strong EPC and large logarithmic average frequency. The T values of Fm-3m-PaH decrease with increasing pressure. Interestingly, superconducting PaH appears at low pressure, prompting experimental research.
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http://dx.doi.org/10.1088/1361-648X/ab1d03DOI Listing
August 2019

Unique Phase Diagram and Superconductivity of Calcium Hydrides at High Pressures.

Inorg Chem 2019 Feb 7;58(4):2558-2564. Epub 2019 Feb 7.

State Key Laboratory of Superhard Materials, College of Physics , Jilin University , Changchun 130012 , P. R. China.

Structure prediction studies on Ca-H binary systems under high pressures were carried out, and the structures of calcium hydrides in earlier works were reproduced. The previously unreported composition of CaH was found to be stable and experienced the phase transition series Cm → P2/ m → C2/ m from 100 to 400 GPa. To the best of our knowledge, CaH may be the only alkaline earth hydride with an odd H content. At 400 GPa, the metastable R3̅ m-CaH phase shares the same space group with the R3̅ m-SrH phase with puckered honeycomb H layers. The C2/ m phase of CaH and the R3̅ m phase of CaH are excellent superconductors with T values of about 240-266 and 157-175 K at 300 and 400 GPa, respectively. The high contributions of H-derived states at the Fermi level play an important role in the superconductivity of calcium hydrides.
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http://dx.doi.org/10.1021/acs.inorgchem.8b03165DOI Listing
February 2019

High-Pressure Bonding Mechanism of Selenium Nitrides.

Inorg Chem 2019 Feb 5;58(4):2397-2402. Epub 2019 Feb 5.

State Key Laboratory of Superhard Materials , Jilin University , Changchun 130012 , China.

The high-pressure phase diagrams of binary Se-N system have been constructed using the CALYPSO method and first-principles calculations. Four stable compounds ( Cmc2-SeN, P2 /m-SeN, P1̅-SeN, and P1̅-SeN) were identified at high pressures. Various peculiar nitrogen polymerization forms composed of single/double nitrogen-nitrogen bonds were found at the nitrogen-rich condition, such as N-chains in P2/ m-SeN, oligomeric N-chains in P1̅-SeN, and distorted N anion rings in P1̅-SeN. Peculiar nitrogen polymerization forms make these compounds potential high-energy-density materials (HEDMs). Especially, P1̅-SeN has the highest energy density of 4.08 kJ g among the selenium nitrides. The polymerization mechanism of nitrogen in the Se-N system has been explored using the "Lewis-like" two-center-two-electron and three-center-two-electron bonding analysis. Using the nitrogen-rich P1̅-SeN as a prototype, it is found that the famous N distortion in the polymerized nitrogen HEDM can be explained by the interatomic mechanical unbalance which is induced by the three-center two-electron bonding between the metal atom and the two neighboring nitrogen atoms.
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http://dx.doi.org/10.1021/acs.inorgchem.8b02889DOI Listing
February 2019

A Dual Ionic Liquid-Based Low-Temperature Electrolyte System.

J Phys Chem B 2018 Dec 29;122(50):12077-12086. Epub 2018 Nov 29.

Department of Mechanical and Aerospace Engineering , Hong Kong University of Science and Technology , Clear Water Bay, Kowloon , Hong Kong.

Ionic liquids (ILs) show a promising future as electrolytes in electrochemical devices. In particular, IL-based electrolytes bring operations at extreme temperatures to realization that conventional electrolytes fail to accomplish. Although IL electrolytes demonstrate considerable progress in high-temperature applications, their breakthroughs in devices operating at low temperatures are still very limited due to undesirable phase transitions and unsatisfying transport properties. In this study, we present an approach where, by tuning molecular interactions in the system, the designed electrolyte of an IL-based mixture can reach a lower operating temperature with improved transport properties. We have discovered that the incorporation of the IL, ethylammonium nitrate ([EA][N]), can contribute to reforming the molecular interactions within the system, which effectively resolve the crystallization accompanied with the excess of water and retain a low glass transition temperature. The reported liquid electrolyte systems based on a mixture of 1-butyl-3-methylimidazolium iodide ([BMIM][I]), [EA][N], water, and lithium iodide exhibit a glass transition temperature below -105 °C. Furthermore, the optimized electrolyte system shows significant viscosity reduction and ionic conductivity enhancement from 25 to -75 °C. The influence is also noticeable on the increased ionicity, which made the developed electrolyte comparable with other good ILs under the Walden rule. The electrochemical stability of the electrolyte system is revealed by a steady and reproducible profile of iodide/triiodide redox reactions at room temperature over a proper potential window via cyclic voltammetry. The results from this work not only provide a potential solution to applications of the iodide/triiodide redox couple-based electrochemical devices at low temperatures but also show a practical approach to obtain tailored properties of a mixture system via modifying molecular interactions.
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http://dx.doi.org/10.1021/acs.jpcb.8b08815DOI Listing
December 2018

Hemodynamic simulation of intracranial aneurysm growth with virtual silk stent implantation.

Comput Methods Biomech Biomed Engin 2018 Oct 26:1-10. Epub 2018 Oct 26.

a Capital Medical University , School of Biomedical Engineering, Beijing Key Laboratory of Fundamental Research on Biomechanics in Clinical Application , Beijing , China.

Longitudinal hemodynamic assessment of intracranial aneurysms (IAs) with endovascular treatment is essential for clinical decision making. We proposed a hemodynamic simulation method to explore the hemodynamic characteristics of a certain growth process of IA with virtual Silk stent implantation. Eight growth point models of IA were created by applying a bidirectional linear growing algorithm on patient 3D rotational angiography images. Simulated experiments showed that the WSS and velocity were significantly decreased with virtual Silk stent implantation at all growth points considered. The simulations revealed the flow pattern and WSS characteristics of IA growth.
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http://dx.doi.org/10.1080/10255842.2018.1490953DOI Listing
October 2018

Tunable Water Harvesting Surfaces Consisting of Biphilic Nanoscale Topography.

ACS Nano 2018 11 24;12(11):11022-11030. Epub 2018 Oct 24.

Department of Mechanical and Aerospace Engineering , The Hong Kong University of Science and Technology , Hong Kong , China.

Water scarcity has become a global issue of severe concern. Great efforts have been undertaken to develop low-cost and highly efficient condensation strategies to relieve water shortages in arid regions. However, the rationale for design of an ideal condensing surface remains lacking due to the conflicting requirements for water nucleation and transport. In this work, we demonstrate that a biphilic nanoscale topography created by a scalable surface engineering method can achieve an ultraefficient water harvesting performance. With hydrophilic nanobumps on top of a superhydrophobic substrate, this biphilic topography combines the merits of biological surfaces with distinct wetting features (e.g., fog-basking beetles and water-repellent lotus), which enables a tunable water nucleation phenomenon, in contrast to the random condensation mode on their counterparts. By adjusting the contrasting wetting features, the characteristic water nucleation spacing can be tuned to balance the nucleation enhancement and water transport to cope with various environments. Guided by our nucleation density model, we show an optimal biphilic topography by tuning the nanoscale hydrophilic structure density, which allows an ∼349% water collection rate and ∼184% heat transfer coefficient as compared to the state-of-the-art superhydrophobic surface in a moisture-lacking atmosphere, offering a very promising strategy for improving the efficiency of water harvesting in drought areas.
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http://dx.doi.org/10.1021/acsnano.8b05163DOI Listing
November 2018

A noninvasive indicator for the diagnosis of early hepatitis B virus-related liver fibrosis.

Eur J Gastroenterol Hepatol 2019 02;31(2):218-223

Departments of Pathology.

Background And Aims: Liver stiffness measurement (LSM) detected by FibroScan, combined with biochemical indexes, has shown potential values for assessment of liver fibrosis pathological degrees. Here we aimed to investigate a noninvasive method for hepatitis B virus-related liver fibrosis.

Patients And Methods: In all, 307 patients who underwent liver biopsy and LSM measurement were included. Inflammation grades and fibrosis stages were evaluated according to METAVIR scoring system. Spearman's rank correlation analysis, logistic regression analysis, and receiver operating characteristic (ROC) curves analysis were performed to assess the factors' role in inflammation grades/fibrosis stages.

Results: Spearman's rank correlation analysis showed that LSM, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and AST-to-platelet ratio index were positively correlated with inflammation grades and histologic fibrosis stages; platelets showed negative correlation, and AST-to-ALT ratio was not related. Logistic regression analysis indicated that LSM and APRI were risk factors for inflammation grades; LSM was the independent risk factor for fibrosis stages, P<0.0001, odds ratio>1. ROC curve analysis found LSM cutoff values and areas under the curve for the diagnosis of fibrosis scores: 6.95 and 0.804, respectively, for the diagnosis of significant fibrosis (F≥F2); 10.35 and 0.856, respectively, for severe fibrosis (F≥F3); 11.35 and 0.897, respectively, for cirrhosis (F=F4). Considering ALT as a confounding factor, ROC analysis was repeated in patients with normal and elevated ALT separately; the results indicated that when ALT was up to 40 U/l, LSM cutoff value and areas under the curve for the diagnosis of significant fibrosis (F≥F2) were 6.55 and 0.748, respectively.

Conclusion: This study provided a noninvasive treatment and prevention indicator for early hepatitis B virus-related liver fibrosis.
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http://dx.doi.org/10.1097/MEG.0000000000001281DOI Listing
February 2019

Stable structures and superconductivity of an At-H system at high pressure.

Phys Chem Chem Phys 2018 Oct;20(38):24783-24789

State Key Laboratory of Superhard Materials, College of Physics, Jilin University, Changchun, 130012, P. R. China.

The phase diagram, electronic properties and superconductivity of an At-H system at high pressure are investigated through first principles calculation considering the effect of spin-orbit coupling (SOC). The Cmcm-AtH2, Pnma-AtH2, P6/mmm-AtH4, and Cmmm-AtH4 phases are uncovered above 50 GPa. Metallization is realized at 50 GPa for AtH2 and 60 GPa for AtH4, with Tc values of approximately 5-10 K and 30-50 K, respectively. In P6/mmm-AtH4, phonon softening induced by Fermi surface nesting occurs as the pressure increases, which is closely related to the structural phase transition of P6/mmm → Cmmm and plays a crucial role in the superconductivity of the P6/mmm phase. In addition, the spin-orbit coupling effect considerably influences the energy of ground states, pressure points of phase transitions, electronic structures, and even the electron-phonon coupling of the At-H system. Such an influence may also occur in other heavy atomic hydrides.
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http://dx.doi.org/10.1039/c8cp04317eDOI Listing
October 2018

Insights into Antibonding Induced Energy Density Enhancement and Exotic Electronic Properties for Germanium Nitrides at Modest Pressures.

Inorg Chem 2018 Aug 9;57(16):10416-10423. Epub 2018 Aug 9.

State Key Laboratory of Superhard Materials , Jilin University , Changchun 130012 , China.

Here, the electronic and bonding features in ground-state structures of germanium nitrides under different components that not accessible at ambient conditions have been systematically studied. The forming essence of weak covalent bonds between the Ge and N atom in high-pressure ionic crystal Fd-3 m-GeN is induced by the binding effect of electronic clouds originated from the Ge_ p orbitals. Hence, it helps us to understand the essence of covalent bond under high pressure, profoundly. As an excellent reducing agent, germanium transfer electrons to the antibonding state of the N dimer in Pa-3-GeN phase at 20 GPa, abnormally, weakening the bonding strength considerably than nitrogen gap (N≡N) at ambient pressure. Furthermore, the common cognition that the atomic distance will be shortened under the high pressures has been broken. Amazingly, with a lower range of synthetic pressure (∼15 GPa) and nitrogen contents (28%), its energy density is up to 2.32 kJ·g, with a similar order of magnitude than polymeric LiN (nonmolecular compound, 2.72 kJ·g). It breaks the universal recognition once again that nitrides just containing polymeric nitrogen were regarded as high energy density materials. Hence, antibonding induced energy density enhancement mechanism for low nitrogen content and pressure has been exposed in view of electrons. Both the highest occupied molecular orbitals (HOMO) and the lowest unoccupied molecular orbitals (LUMO) are usually the separated orbitals of N_π* and N_σ*, which are the key to stabilization. Besides, the sp hybridizations that exist in N units are responsible for the stability of the R-3 c-GeN structure and restrict the delocalization of electrons, exhibiting nonmetallic properties.
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http://dx.doi.org/10.1021/acs.inorgchem.8b01669DOI Listing
August 2018