Publications by authors named "He Tian"

627 Publications

Electron-enriched thione enables strong Pb-S interaction for stabilizing high quality CsPbI perovskite films with low-temperature processing.

Chem Sci 2020 Feb 17;11(12):3132-3140. Epub 2020 Feb 17.

Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Feringa Nobel Prize Scientist Joint Research Center, Shanghai Key Laboratory of Functional Materials Chemistry, Institute of Fine Chemicals, School of Chemistry and Molecular Engineering, East China University of Science and Technology Shanghai 200237 China

Cesium lead iodide (CsPbI) perovskite is a promising photovoltaic material with a suitable bandgap and high thermal stability. However, it involves complicated phase transitions, and black-phase CsPbI is mostly formed and stabilized at high temperatures (200-360 °C), making its practical application challenging. Here, for the first time, we have demonstrated a feasible route for growing high quality black-phase CsPbI thin films under mild conditions by using a neutral molecular additive of 4(1)-pyridinethione (4-PT). The resulting CsPbI thin films are morphologically uniform and phase stable under ambient conditions, consisting of micron-sized grains with oriented crystal stacking. With a range of characterization experiments on intermolecular interactions, the electron-enriched thione group in 4-PT is distinguished to be critical to enabling a strong Pb-S interaction, which not only influences the crystallization paths, but also stabilizes the black-phase CsPbI crystal surface functionalization. The 4-PT based CsPbI achieves 13.88% power conversion efficiency in a p-i-n structured device architecture, and encapsulated devices can retain over 85% of their initial efficiencies after 20 days of storage in an ambient environment, which are the best results among fully low-temperature processed CsPbI photovoltaics.
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http://dx.doi.org/10.1039/c9sc06574aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157470PMC
February 2020

Cucurbiturils brighten Au nanoclusters in water.

Chem Sci 2020 Mar 6;11(13):3531-3537. Epub 2020 Mar 6.

Key Laboratory for Advanced Materials, Feringa Nobel Prize Scientist Joint Research Center, Institute of Fine Chemicals, School of Chemistry and Molecular Engineering, East China University of Science & Technology 130 Meilong Road Shanghai 200237 China

Gold nanoclusters (AuNCs) with well-defined atomically precise structures present promising emissive prospects for excellent biocompatibility and optical properties. However, the relatively low luminescence efficiency in solutions for most AuNCs is still a perplexing issue to be resolved. In this study, a facile supramolecular strategy was developed to rigidify the surface of FGGC-AuNCs by modifying transition rates in excited states host-guest self-assembly between cucurbiturils (CBs) and FGGC (Phe-Gly-Gly-Cys peptide). In aqueous solutions, CB/FGGC-AuNCs presented an extremely enhanced red phosphorescence emission with a quantum yield (QY) of 51% for CB[7] and 39% for CB[8], while simple FGGC-AuNCs only showed a weak emission with a QY of 7.5%. Furthermore, CB[7]/FGGC-AuNCs showed excellent results in live cell luminescence imaging for A549 cancer cells. Our study demonstrates that host-guest self-assembly assisted by macrocycles is a facile and effective tool to non-covalently modify and adjust optical properties of nanostructures on ultra-small scales.
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http://dx.doi.org/10.1039/d0sc00473aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8152592PMC
March 2020

Highly efficient electrocatalytic hydrogen evolution promoted by O-Mo-C interfaces of ultrafine β-MoC nanostructures.

Chem Sci 2020 Mar 12;11(13):3523-3530. Epub 2020 Mar 12.

Department of Chemistry, University of South Florida 4202 E. Fowler Avenue Tampa Florida 33620 USA

Optimizing interfacial contacts and thus electron transfer phenomena in heterogeneous electrocatalysts is an effective approach for enhancing electrocatalytic performance. Herein, we successfully synthesized ultrafine β-MoC nanoparticles confined within hollow capsules of nitrogen-doped porous carbon (β[email protected]) and found that the surface layer of molybdenum atoms was further oxidized to a single Mo-O surface layer, thus producing intimate O-Mo-C interfaces. An arsenal of complementary technologies, including XPS, atomic-resolution HAADF-STEM, and XAS analysis clearly reveals the existence of O-Mo-C interfaces for these surface-engineered ultrafine nanostructures. The β[email protected] electrocatalyst exhibited excellent electrocatalytic activity for the hydrogen evolution reaction (HER) in water. Theoretical studies indicate that the highly accessible ultrathin O-Mo-C interfaces serving as the active sites are crucial to the HER performance and underpinned the outstanding electrocatalytic performance of β[email protected] This proof-of-concept study opens a new avenue for the fabrication of highly efficient catalysts for HER and other applications, whilst further demonstrating the importance of exposed interfaces and interfacial contacts in efficient electrocatalysis.
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http://dx.doi.org/10.1039/d0sc00427hDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8152622PMC
March 2020

Gate-Tunable Negative Differential Resistance Behaviors in a hBN-Encapsulated BP-MoS Heterojunction.

ACS Appl Mater Interfaces 2021 Jun 25;13(22):26161-26169. Epub 2021 May 25.

Institute of Microelectronics and Beijing National Research Center for Information Science and Technology (BNRist), Tsinghua University, Beijing 100084, China.

Two-dimensional (2D) heterostructures show great potential in achieving negative differential resistance (NDR) effects by Esaki diodes and or resonant tunneling diodes. However, most of the reported Esaki diode-based NDR devices realized by bulk 2D films lack sufficient gate tunability, and the tuning of NDR behavior from appearing to vanishing remains elusive. Here, a gate-tunable NDR device is reported based on a vertically stacked black phosphorus (BP) and molybdenum disulfide (MoS) thin 2D heterojunction. At room temperature, a rectifying ratio of ∼6 orders of magnitude from a reverse rectifying diode to a forward rectifying diode by gate modulation is obtained. Through analyzing the temperature-dependent electrical properties, the tunneling mechanism at a certain gate voltage range is revealed. Moreover, the switchable and continuously gate-tunable NDR behavior is realized with a maximum peak-to-valley ratio of 1.23 at 77 K, as shown in the mappings by sweeping under different . In addition, a compact model for gate-tunable NDR behavior in 2D heterostructures is proposed. To our best knowledge, this is the first demonstration of NDR behavior in BP-MoS heterostructures. Consequently, this work sheds light on the gate-tunable NDR devices and reconfigurable logic devices for realizing ternary and reconfigurable logic systems.
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http://dx.doi.org/10.1021/acsami.1c03959DOI Listing
June 2021

Electric field control of superconductivity at the LaAlO/KTaO(111) interface.

Science 2021 05;372(6543):721-724

Interdisciplinary Center for Quantum Information, State Key Laboratory of Modern Optical Instrumentation, and Zhejiang Province Key Laboratory of Quantum Technology and Device, Department of Physics, Zhejiang University, Hangzhou 310027, China.

The oxide interface between LaAlO and KTaO(111) can harbor a superconducting state. We report that by applying a gate voltage () across KTaO, the interface can be continuously tuned from superconducting into insulating states, yielding a dome-shaped - dependence, where is the transition temperature. The electric gating has only a minor effect on carrier density but a strong one on mobility. We interpret the tuning of mobility in terms of change in the spatial profile of the carriers in the interface and hence, effective disorder. As the temperature is decreased, the resistance saturates at the lowest temperature on both superconducting and insulating sides, suggesting the emergence of a quantum metallic state associated with a failed superconductor and/or fragile insulator.
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http://dx.doi.org/10.1126/science.abb3848DOI Listing
May 2021

PD-L1 and CD47 co-expression predicts survival and enlightens future dual-targeting immunotherapy in non-small cell lung cancer.

Thorac Cancer 2021 Jun 12;12(11):1743-1751. Epub 2021 May 12.

Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

Backgroud: Recent studies have indicated that programmed cell death-ligand 1 (PD-L1) and cluster of differentiation 47 (CD47) play an essential role in tumor immune evasion and may serve as potential targets for combined immunotherapy. The aim of our study was to evaluate the PD-L1/CD47 expression status in lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD), and explore its survival impact and relevance with the immune microenvironment.

Methods: The specimens from 190 LUSC and 240 LUAD patients who underwent intent-to-treat surgeries were retrospectively collected for immunohistochemistry assays of PD-L1, CD47, cluster of differentiation 8 (CD8), and cluster of differentiation 68 (CD68).

Results: A total of 96 (22.3%) and 296 (68.8%) cases were positive for PD-L1 and CD47 expression, respectively, and 80 (18.6%) of them demonstrated the co-expression of PD-L1/CD47. The rate of PD-L1/CD47 co-expression was 23.7% in LUSC, significantly higher than the 14.6% in LUAD (p = 0.018). The median overall survival (OS) for all patients was 55.9 months (range 2.0-146.0 months). The univariate analysis showed that patients with positive CD47 expression (LUSC p = 0.003, LUAD p = 0.036) and PD-L1/CD47 co-expression (LUSC p = 0.023, LUAD p = 0.004) exhibited significantly worse prognosis. The multivariate analysis demonstrated that PD-L1/CD47 co-expression was an independent prognostic factor for OS (LUSC hazard ratio [HR] 1.922, 95% CI 1.245-2.969, p = 0.003; LUAD HR 1.549, 95% CI 1.015-2.364, p = 0.043). PD-L1/CD47 co-expression was associated with high CD8-positive T-lymphocyte density in LUSC (p = 0.004) and LUAD (p = 0.043), and with high CD68-positive macrophage density in LUSC (p = 0.026).

Conclusions: PD-L1/CD47 co-expression was an independent prognostic factor for LUSC and LUAD patients and may serve as a potential predictive biomarker for combined dual-targeting immunotherapy.
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http://dx.doi.org/10.1111/1759-7714.13989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169290PMC
June 2021

Comprehensive analysis of a chemokine- and chemokine receptor family-based signature for patients with lung adenocarcinoma.

Cancer Immunol Immunother 2021 May 11. Epub 2021 May 11.

Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.

The clinical significance and comprehensive features of chemokines and their receptors in lung adenocarcinoma (LUAD) have not been clarified. We aimed to characterize the expression profiles of chemokine and chemokine receptor family members and construct a chemokine- and chemokine receptor-based prognosis signature. A total of 1511 patients with LUAD from seven independent cohorts were included in the study. The training set collected from The Cancer Genome Atlas (TCGA) database containing 468 cases. The validation was performed on the basis of six different cohorts downloaded from Gene Expression Omnibus (GEO) database. A five-chemokine- and chemokine receptor-(CXCL2, CXCL13, CCL26, CCL20, CX3CR1) based prognosis signature was constructed with TCGA dataset using LASSO Cox regression and Cox proportional hazards regression analysis. A multivariate analysis verified that this signature was an independent prognostic factor. The predictive value of this signature was further verified by other six independent cohorts and multiple clinical subtypes. We performed immune cell infiltration analysis and biological pathway analysis which provided more insight into this signature-related immune and inflammatory landscape and clarified the intrinsic molecular mechanism by which this signature could be used to predict clinical prognosis. Furthermore, we explored the close relationship between this signature and tumor mutation burden (TMB), neoantigen burden, PD-1, PD-L1, CTLA4, TIDE score, T cell-inflamed score. This signature provided a robust prognostic biomarker for LUAD and could serve as a predictor for immunotherapy response, which may be used as an important supplement to immunotherapy to achieve individualized tumor treatment by optimizing the prognostic management and immunotherapy for patients with LUAD.
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http://dx.doi.org/10.1007/s00262-021-02944-1DOI Listing
May 2021

Engendering persistent organic room temperature phosphorescence by trace ingredient incorporation.

Sci Adv 2021 May 7;7(19). Epub 2021 May 7.

Key Laboratory for Advanced Materials and Feringa Nobel Prize Scientist Joint Research Center, Frontiers Science Center for Materiobiology and Dynamic Chemistry, School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai 200237, P. R. China.

Pure organic persistent room temperature phosphorescence (RTP) has shown great potential in information encryption, optoelectronic devices, and bio-applications. However, trace impurities are generated in synthesis, causing unpredictable effects on the luminescence properties. Here, an impurity is isolated from a pure organic RTP system and structurally characterized that caused an unusual ultralong RTP in matrix even at 0.01 mole percent content. Inspired by this effect, a series of compounds are screened out to form the bicomponent RTP system by the trace ingredient incorporation method. The RTP quantum yields reach as high as 74.2%, and the lifetimes reach up to 430 ms. Flexible application of trace ingredients to construct RTP materials has become an eye-catching strategy with high efficiency, economy, and potential for applications as well as easy preparation.
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http://dx.doi.org/10.1126/sciadv.abf9668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8104869PMC
May 2021

Motorized Macrocycle: A Photo-responsive Host with Switchable and Stereoselective Guest Recognition.

Angew Chem Int Ed Engl 2021 May 6. Epub 2021 May 6.

Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Feringa Nobel Prize Scientist Joint Research Center, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Institute of Fine Chemicals, School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai, 200237, China.

Designing photo-responsive host-guest systems can provide versatile supramolecular tools for constructing smart systems and materials. We designed photo-responsive macrocyclic hosts, modulated by light-driven molecular rotary motors enabling switchable chiral guest recognition. The intramolecular cyclization of the two arms of a first-generation molecular motor with flexible oligoethylene glycol chains of different lengths resulted in crown-ether-like macrocycles with intrinsic motor function. The octaethylene glycol linkage enables the successful unidirectional rotation of molecular motors, simultaneously allowing the 1:1 host-guest interaction with ammonium salt guests. The binding affinity and stereoselectivity of the motorized macrocycle can be reversibly modulated, owing to the multi-state light-driven switching of geometry and helicity of the molecular motors. This approach provides an attractive strategy to construct stimuli-responsive host-guest systems and dynamic materials.
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http://dx.doi.org/10.1002/anie.202104285DOI Listing
May 2021

Photoactivated voltage imaging in tissue with an archaerhodopsin-derived reporter.

Sci Adv 2021 May 5;7(19). Epub 2021 May 5.

Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.

Photoactivated genetically encoded voltage indicators (GEVIs) have the potential to enable optically sectioned voltage imaging at the intersection of a photoactivation beam and an imaging beam. We developed a pooled high-throughput screen to identify archaerhodopsin mutants with enhanced photoactivation. After screening ~10 cells, we identified a novel GEVI, NovArch, whose one-photon near-infrared fluorescence is reversibly enhanced by weak one-photon blue or two-photon near-infrared excitation. Because the photoactivation leads to fluorescent signals catalytically rather than stoichiometrically, high fluorescence signals, optical sectioning, and high time resolution are achieved simultaneously at modest blue or two-photon laser power. We demonstrate applications of the combined molecular and optical tools to optical mapping of membrane voltage in distal dendrites in acute mouse brain slices and in spontaneously active neurons in vivo.
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http://dx.doi.org/10.1126/sciadv.abe3216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099184PMC
May 2021

Zinc attenuates ferroptosis and promotes functional recovery in contusion spinal cord injury by activating Nrf2/GPX4 defense pathway.

CNS Neurosci Ther 2021 May 5. Epub 2021 May 5.

Department of Orthopedics, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.

Aim: Spinal cord injury (SCI) involves multiple pathological processes. Ferroptosis has been shown to play a critical role in the injury process. We wanted to explore whether zinc can inhibit ferroptosis, reduce inflammation, and then exert a neuroprotective effect.

Methods: The Alice method was used to establish a spinal cord injury model. The Basso Mouse Scale (BMS), Nissl staining, hematoxylin-eosin staining, and immunofluorescence analysis were used to investigate the protective effect of zinc on neurons on spinal cord neurons and the recovery of motor function. The regulation of the nuclear factor E2/heme oxygenase-1 (NRF2/HO-1) pathway was assessed, the levels of essential ferroptosis proteins were measured, and the changes in mitochondria were confirmed by transmission electron microscopy and 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-imidacarbocyanine iodide (JC-1) staining. In vitro experiments using VSC4.1 (spinal cord anterior horn motor neuroma cell line), 4-hydroxynonenal (4HNE), reactive oxygen species (ROS), superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), lipid peroxides, and finally the levels of inflammatory factors were detected to assess the effect of zinc.

Results: Zinc reversed behavioral and structural changes after SCI. Zinc increased the expression of NRF2/HO-1, thereby increasing the content of glutathione peroxidase 4 (GPX4), SOD, and GHS and reducing the levels of lipid peroxides, MDA, and ROS. Zinc also rescued injured mitochondria and effectively reduced spinal cord injury and the levels of inflammatory factors, and the NRF2 inhibitor Brusatol reversed the effects of zinc.

Conclusion: Zinc promoted the degradation of oxidative stress products and lipid peroxides through the NRF2/HO-1 and GPX4 signaling pathways to inhibit ferroptosis in neurons.
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http://dx.doi.org/10.1111/cns.13657DOI Listing
May 2021

[Effects of water quality on the reproductive behavior and capacity of under tourism disturbance.]

Ying Yong Sheng Tai Xue Bao 2021 Apr;32(4):1471-1478

Zhangjiajie Zhuyuan Biological Technology of Chinese Giant Salamander Co. Ltd., Zhangjiajie 427400, Hunan, China.

Water quality under tourism disturbance was simulated through controlling the water intake of the ecological breeding ponds of Chinese giant salamander (, CGS). Both the reproductive behavior (oviposition and parental care) and capacity (relative egg production, fertilizing rate of eggs, and hatching rate of fertilized eggs) of CGS were examined using a real-time infrared digital monitoring system. The relationships among reproductive behavior, capacity, and the corresponding parameters of water quality were analyzed, to understand how water quality under tourism disturbance would affect the reproductive behavior and capacity of CGS. The examined oviposition behavior and capacity of CGS showed no variation in general, but the parental care behavior such as tail fanning and agitation time of the male CGS were prolonged significantly in the groups under tourism disturbance. Such prolonged behaviors would help increase the content of dissolved oxygen (DO) to meet the high demands of DO during embryonic development of CGS. In addition, the overall hatching time of fertilized eggs was increased significantly under disturbance conditions when it compared with the control, which would ensure the overall hatching rate among these comparative groups unaffected. In summary, the prolongations of some reproductive behavior (tail fanning and agitation of the male CGS and the development time of fertilized egg) would be a kind of positive actions of CGS in response to the changes of water quality resulted from tourism disturbance.
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http://dx.doi.org/10.13287/j.1001-9332.202104.035DOI Listing
April 2021

Stepwise selection of natural variations at CTB2 and CTB4a improves cold adaptation during domestication of japonica rice.

New Phytol 2021 Apr 23. Epub 2021 Apr 23.

State Key Laboratory of Agrobiotechnology/Beijing Key Laboratory of Crop Genetic Improvement, College of Agronomy and Biotechnology, China Agricultural University, Beijing, 100193, China.

The improvement of cold adaptation has contributed to the increased growing area of rice. Standing variation and de novo mutation are distinct natural sources of beneficial alleles in plant adaptation. However, the genetic mechanisms and evolutionary patterns underlying these sources in a single population during crop domestication remain elusive. Here we cloned the CTB2 gene, encoding a UDP-glucose sterol glucosyltransferase, for cold tolerance in rice at the booting stage. A single standing variation (I408V) in the conserved UDPGT domain of CTB2 originated from Chinese Oryza rufipogon and contributed to the cold adaptation of Oryza sativa ssp. japonica. CTB2 is located in a 56.8 kb region, including the previously reported gene CTB4a in which de novo mutation arose c. 3200 yr BP in Yunnan province, China, conferring cold tolerance. Standing variation of CTB2 and de novo mutation of CTB4a underwent stepwise selection to facilitate cold adaptation to expand rice cultivation from high-altitude to high-latitude regions. These results provide an example of stepwise selection on two kinds of variation and describe a new molecular mechanism of cold adaptation in japonica rice.
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http://dx.doi.org/10.1111/nph.17407DOI Listing
April 2021

A multi-tissue multi-omics analysis reveals distinct kineztics in entrainment of diurnal transcriptomes by inverted feeding.

iScience 2021 Apr 19;24(4):102335. Epub 2021 Mar 19.

Department of Cardiology and the Center for Circadian Metabolism and Cardiovascular Disease, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China.

Time of eating synchronizes circadian rhythms of metabolism and physiology. Inverted feeding can uncouple peripheral circadian clocks from the central clock located in the suprachiasmatic nucleus. However, system-wide changes of circadian metabolism and physiology entrained to inverted feeding in peripheral tissues remain largely unexplored. Here, we performed a 24-h global profiling of transcripts and metabolites in mouse peripheral tissues to study the transition kinetics during inverted feeding, and revealed distinct kinetics in phase entrainment of diurnal transcriptomes by inverted feeding, which graded from fat tissue (near-completely entrained), liver, kidney, to heart. Phase kinetics of tissue clocks tracked with those of transcriptomes and were gated by light-related cues. Integrated analysis of transcripts and metabolites demonstrated that fatty acid oxidation entrained completely to inverted feeding in heart despite the slow kinetics/resistance of the heart clock to entrainment by feeding. This multi-omics resource defines circadian signatures of inverted feeding in peripheral tissues (www.CircaMetDB.org.cn).
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http://dx.doi.org/10.1016/j.isci.2021.102335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050734PMC
April 2021

A Light-Operated Molecular Cable Car for Gated Ion Transport.

Angew Chem Int Ed Engl 2021 Apr 11. Epub 2021 Apr 11.

Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Feringa Nobel Prize Scientist Joint Research Center, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Institute of Fine Chemicals, School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai, 200237, China.

Inspired by the nontrivial and controlled movements of molecular machines, we report an azobenzene-based molecular shuttle PR2, which can perform light-gated ion transport across lipid membranes. The amphiphilicity and membrane-spanning molecular length enable PR2 to insert into the bilayer membrane and efficiently transport K (EC =4.1 μm) through the thermally driven stochastic shuttle motion of the crown ether ring along the axle. The significant difference in shuttling rate between trans-PR2 and cis-PR2 induced by molecular isomerization enables a light-gated ion transport, i.e., ON/OFF in situ regulation of transport activity and single-channel current. This work represents an example of using a photoswitchable molecular machine to realize gated ion transport, which demonstrates the value of molecular machines functioning in biomembranes.
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http://dx.doi.org/10.1002/anie.202102838DOI Listing
April 2021

A Novel Immune-Related Prognostic Model for Response to Immunotherapy and Survival in Patients With Lung Adenocarcinoma.

Front Cell Dev Biol 2021 19;9:651406. Epub 2021 Mar 19.

Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.

Lung adenocarcinoma is one of the most malignant diseases worldwide. The immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) and programmed cell death-ligand 1 (PD-L1) have changed the paradigm of lung cancer treatment; however, there are still patients who are resistant. Further exploration of the immune infiltration status of lung adenocarcinoma (LUAD) is necessary for better clinical management. In our study, the CIBERSORT method was used to calculate the infiltration status of 22 immune cells in LUAD patients from The Cancer Genome Atlas (TCGA). We clustered LUAD based on immune infiltration status by consensus clustering. The differentially expressed genes (DEGs) between cold and hot tumor group were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed. Last, we constructed a Cox regression model. We found that the infiltration of M0 macrophage cells and follicular helper T cells predicted an unfavorable overall survival of patients. Consensus clustering of 22 immune cells identified 5 clusters with different patterns of immune cells infiltration, stromal cells infiltration, and tumor purity. Based on the immune scores, we classified these five clusters into hot and cold tumors, which are different in transcription profiles. Hot tumors are enriched in cytokine-cytokine receptor interaction, while cold tumors are enriched in metabolic pathways. Based on the hub genes and prognostic-related genes, we developed a Cox regression model to predict the overall survival of patients with LUAD and validated in other three datasets. In conclusion, we developed an immune-related signature that can predict the prognosis of patients, which might facilitate the clinical application of immunotherapy in LUAD.
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http://dx.doi.org/10.3389/fcell.2021.651406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017122PMC
March 2021

Serine metabolism antagonizes antiviral innate immunity by preventing ATP6V0d2-mediated YAP lysosomal degradation.

Cell Metab 2021 May 1;33(5):971-987.e6. Epub 2021 Apr 1.

Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China; Department of Pharmacology and Tianjin Key Laboratory of Inflammation Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China; The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China. Electronic address:

Serine metabolism promotes tumor oncogenesis and regulates immune cell functions, but whether it also contributes to antiviral innate immunity is unknown. Here, we demonstrate that virus-infected macrophages display decreased expression of serine synthesis pathway (SSP) enzymes. Suppressing the SSP key enzyme phosphoglycerate dehydrogenase (PHGDH) by genetic approaches or by treatment with the pharmaceutical inhibitor CBR-5884 and by exogenous serine restriction enhanced IFN-β-mediated antiviral innate immunity in vitro and in vivo. Mechanistic experiments showed that virus infection or serine metabolism deficiency increased the expression of the V-ATPase subunit ATP6V0d2 by inhibiting S-adenosyl methionine-dependent H3K27me3 occupancy at the promoter. ATP6V0d2 promoted YAP lysosomal degradation to relieve YAP-mediated blockade of the TBK1-IRF3 axis and, thus, enhance IFN-β production. These findings implicate critical functions of PHGDH and the key immunometabolite serine in blunting antiviral innate immunity and also suggest manipulation of serine metabolism as a therapeutic strategy against virus infection.
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http://dx.doi.org/10.1016/j.cmet.2021.03.006DOI Listing
May 2021

Identification and Characterization of EvpQ, a Novel T6SS Effector Encoded on a Mobile Genetic Element in .

Front Microbiol 2021 11;12:643498. Epub 2021 Mar 11.

State Key Laboratory of Freshwater Ecology and Biotechnology, Key Laboratory of Aquaculture Disease Control, Ministry of Agriculture, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.

In this study, a hypothetical protein (ORF02740) secreted by was identified. We renamed the ORF02740 protein as EvpQ, which is encoded by a mobile genetic element (MGE) in genome. The gene is spaced by 513 genes from type VI secretion system (T6SS) gene cluster. Low GC content, three tRNA, and three transposase genes nearby define this MGE that localizes as a genomic island. Sequence analysis reveals that EvpQ shares a conserved domain of C70 family cysteine protease and shares 23.91% identity with T3SS effector AvrRpt2 of phytopathogenic Instead, EvpQ of is proved to be secreted at a T6SS-dependent manner, and it can be translocated into host cells. EvpQ is thereof a novel T6SS effector. Significantly decreased competitive index of Δ strain in blue gourami fish (0.53 ± 0.27 in head kidney and 0.44 ± 0.19 in spleen) indicates that EvpQ contributes to the pathogenesis of . At 8-, 18-, and 24-h post-subculture into DMEM, the transcription of was found to be negatively regulated by Fur and positively regulated by EsrC, and the steady-state protein levels of EvpQ are negatively controlled by RpoS. Our study lays a foundation for further understanding the pathogenic role of T6SS in edwardsiellosis.
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http://dx.doi.org/10.3389/fmicb.2021.643498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7991086PMC
March 2021

Interface-engineered electron and hole tunneling.

Sci Adv 2021 Mar 24;7(13). Epub 2021 Mar 24.

Department of Materials Science and Engineering, National University of Singapore, 117575 Singapore, Singapore.

Although the phenomenon of tunneling has been known since the advent of quantum mechanics, it continues to enrich our understanding of many fields of science. Commonly, this effect is described in terms of electrons traversing the potential barrier that exceeds their kinetic energy due to the wave nature of electrons. This picture of electron tunneling fails, however, for tunnel junctions, where the Fermi energy lies sufficiently close to the insulator valence band, in which case, hole tunneling dominates. We demonstrate the deterministic control of electron and hole tunneling in interface-engineered Pt/BaTiO/LaSrMnO ferroelectric tunnel junctions by reversal of tunneling electroresistance. Our electrical measurements, electron microscopy and spectroscopy characterization, and theoretical modeling unambiguously point out to electron or hole tunneling regimes depending on interface termination. The interface control of the tunneling regime offers designed functionalities of electronic devices.
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http://dx.doi.org/10.1126/sciadv.abf1033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990336PMC
March 2021

Berberine-loaded M2 macrophage-derived exosomes for spinal cord injury therapy.

Acta Biomater 2021 05 17;126:211-223. Epub 2021 Mar 17.

Pharmacy School, Jinzhou Medical University, Jinzhou, China. Electronic address:

Spinal cord injury (SCI) causes immune activation of resident macrophages/microglia. Activated macrophages/microglia have two different phenotypes, the pro-inflammatory classically activated (M1) phenotype and the anti-inflammatory alternatively activated (M2) phenotype. M1 phenotype macrophages/microglia are the key factor in inflammation. The treatment of SCI remains a huge challenge due to the nontargeting and inefficiency of anti-inflammatory drugs through the blood-brain barrier (BBB). The purpose of this experiment was to design M2-type primary peritoneal macrophages exosomes (Exos) as a drug carrier for berberine (Ber), which can be efficiently targeted to deliver drugs to the injured spinal cord due to the natural advantage of Exos across the BBB. The Exos with particle size of 125±12 nm were loaded with by an ultrasonic method and the drug loading reached 17.13 ±1.64%. The Ber release experiment showed that the loaded sample (Exos-Ber) exhibited sustained release effect, and the cumulative release amount reached 71.44±2.86% within 48 h. In vitro and in vivo experiments confirmed that the Exos-Ber could decrease the M1 protein marker iNOS, elevate the M2 protein marker CD206 and reduce inflammatory and apoptotic cytokines (TNF-α, IL-1β, IL-6, Caspase 9, Caspase 8), which showed that Exos-Ber had a good anti-inflammatory and anti-apoptotic effect by inducing macrophages/microglia from the M1 phenotype to M2 phenotype polarization. Moreover, the motor function of SCI mice was significantly improved after Exos-Ber treatment, indicating that Exos-Ber is a potential agent for SCI therapy. STATEMENT OF SIGNIFICANCE: Efficient targeting strategy for drug delivery. In addition to good biocompatibility and stealth ability, M2 macrophage-derived Exosomes present natural inflammatory targeting ability. The inflammatory microenvironment after spinal cord injury provides motivation for the targeting of exosomes. Natural drug carrier with higher safety. With the rapid development of nanomaterials, drug carriers have become more selective. However, due to the special microenvironment after central nervous system damage, some non-degradable inorganic materials will increase the pressure of self-healing and even secondary damage to neurons, which has been solved by the emergence of exosomes. Some previous studies used tumor cell line exosomes as drug carriers, but the carcinogenic factors carried by themselves have extremely high hidden dangers, and endogenous macrophage exosomes have absolute advantages over their safety.
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http://dx.doi.org/10.1016/j.actbio.2021.03.018DOI Listing
May 2021

Efficient and bright warm-white electroluminescence from lead-free metal halides.

Nat Commun 2021 Mar 3;12(1):1421. Epub 2021 Mar 3.

Key Laboratory of Flexible Electronics (KLOFE) & Institute of Advanced Materials (IAM), Nanjing Tech University (NanjingTech), Nanjing, China.

Solution-processed metal-halide perovskites are emerging as one of the most promising materials for displays, lighting and energy generation. Currently, the best-performing perovskite optoelectronic devices are based on lead halides and the lead toxicity severely restricts their practical applications. Moreover, efficient white electroluminescence from broadband-emission metal halides remains a challenge. Here we demonstrate efficient and bright lead-free LEDs based on cesium copper halides enabled by introducing an organic additive (Tween, polyethylene glycol sorbitan monooleate) into the precursor solutions. We find the additive can reduce the trap states, enhancing the photoluminescence quantum efficiency of the metal halide films, and increase the surface potential, facilitating the hole injection and transport in the LEDs. Consequently, we achieve warm-white LEDs reaching an external quantum efficiency of 3.1% and a luminance of 1570 cd m at a low voltage of 5.4 V, showing great promise of lead-free metal halides for solution-processed white LED applications.
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http://dx.doi.org/10.1038/s41467-021-21638-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930043PMC
March 2021

MICAL1 (molecule interacting with CasL 1) protects oligodendrocyte cells from oxidative injury through regulating apoptosis, autophagy in spinal cord injury.

Neurosci Lett 2021 04 26;750:135712. Epub 2021 Feb 26.

Department of Orthopedics, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China. Electronic address:

Molecule's mechanism of action interacting with CasL 1 (MICAL1) in spinal cord injury (SCI) is unclear. This study aimed to detect the function of MICAL1 in SCI. Western blot was used to analyze the change of MICAL1 in vivo. Immunofluorescence staining was used to detect the location of MICAL1 expression. Oligodendrocyte cells were treated with HO to induce oxidative injury. Subsequently, siRNA transfection was performed to decrease MICAL1 expression in oligodendrocyte cells. Then, the effects of MICAL1 on oxidative stress, apoptosis, and autophagy were assessed. We found that silencing of MICAL1 could significantly reduce the levels of the nuclear factor erythroid 2-related factor 2 (Nrf2), increase the expression of pro-apoptotic factors (Bax and C-caspase 3), decrease the levels of anti-apoptotic factor (Bcl-2) and pro-autophagy factors (Beclin1 and LC3B). Therefore, MICAL1 is a potential target gene for SCI clinical therapy.
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http://dx.doi.org/10.1016/j.neulet.2021.135712DOI Listing
April 2021

Resveratrol inhibits LPS-induced apoptosis in VSC4.1 motoneurons through enhancing SIRT1-mediated autophagy.

Iran J Basic Med Sci 2021 Jan;24(1):38-43

Department of Orthopedics, First Affiliated Hospital of Jinzhou Medical University, Liaoning 121000, China.

Objectives: Resveratrol has been recognized as a potential therapeutic drug in spinal cord injury (SCI). Sirtuin 1 (SIRT1) is vital in the regulation of apoptosis and cell stress response. In this research, our purpose was to explore the mechanisms of resveratrol on neuroprotection and to explore the role of SIRT1.

Materials And Methods: We used lipopolysaccharide (LPS) in the VSC4.1 spinal cord neuron cell line to mimic the micro-environment of the injured spinal cord. The apoptosis of VSC4.1 motoneurons was assessed by TUNEL staining, Western blot, and RT-PCR. Immunofluorescence staining was used to observe the expression site of SIRT1, LC3-B, and Beclin-1, and their protein levels were measured by Western blot and RT-PCR.

Results: Our results showed that resveratrol inhibits LPS-induced apoptosis in VSC4.1 motoneurons. Levels of LC3-B, beclin-1, and SIRT1 indicated a significant increase after resveratrol treatment. But, if autophagy was inhibited, apoptosis in VSC4.1 motoneurons significantly increased. When the cells were treated with EX527, a SIRT1 inhibitor, the protein contents of LC3-B and Beclin-1 were suppressed.

Conclusion: Resveratrol inhibits apoptosis through promoting autophagy in VSC4.1 motoneurons. SIRT1 was involved in autophagy activated by resveratrol in VSC4.1 motoneurons.
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http://dx.doi.org/10.22038/ijbms.2020.44534.10416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894637PMC
January 2021

Solid-State Nuclear Magnetic Resonance Identifies Abnormal Calcium Phosphate Formation in Diseased Bones.

ACS Biomater Sci Eng 2021 03 22;7(3):1159-1168. Epub 2021 Feb 22.

Center for Chemistry of High-Performance & Novel Materials, Department of Chemistry, Zhejiang University, Hangzhou 310027, People's Republic of China.

The crystallites of calcium phosphate (CaP) in bones consist of hydroxyl apatite (HA) and amorphous calcium phosphate (ACP). These nanoscale structures of CaP are sculptured by biological bone formation and resorption processes and are one of the crucial factors that determine the overall strength of the constructs. We used one- and two-dimensional H-P solid-state nuclear magnetic resonance (SSNMR) to investigate the nanoscopic structural changes of CaP. Two quantitative measurables are deduced based on the heterogeneous linewidth of P signal and the ratio of ACP to HA, which characterize the mineral crystallinity and the relative proportion of ACP, respectively. We analyzed bones from different murine models of osteopetrosis and osteoporosis and from human samples with osteoporosis and osteoarthritis. It shows that the ACP content increases notably in osteopetrotic bones that are characterized by defective osteoclastic resorption, whereas the overall crystallinity increases in osteoporotic bones that are marked by overactive osteoclastic resorption. Similar pathological characteristics are observed for the sclerotic bones of late-stage osteoarthritis, as compared to those of the osteopetrotic bones. These findings suggest that osteoclast-related bone diseases not only alter the bone density macroscopically but also lead to abnormal formation of CaP crystallites. The quantitative measurement by SSNMR provides a unique perspective on the pathology of bone diseases at the nanoscopic level.
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http://dx.doi.org/10.1021/acsbiomaterials.0c01559DOI Listing
March 2021

Two-Dimensional Superconductivity at the LaAlO_{3}/KTaO_{3}(110) Heterointerface.

Phys Rev Lett 2021 Jan;126(2):026802

Interdisciplinary Center for Quantum Information, State Key Laboratory of Modern Optical Instrumentation, and Zhejiang Province Key Laboratory of Quantum Technology and Device, Department of Physics, Zhejiang University, Hangzhou 310027, China.

We report on the observation of a T_{c}∼0.9  K superconductivity at the interface between LaAlO_{3} film and the 5d transition metal oxide KTaO_{3}(110) single crystal. The interface shows a large anisotropy of the upper critical field, and its superconducting transition is consistent with a Berezinskii-Kosterlitz-Thouless transition. Both facts suggest that the superconductivity is two-dimensional (2D) in nature. The carrier density measured at 5 K is ∼7×10^{13}  cm^{-2}. The superconducting layer thickness and coherence length are estimated to be ∼8 and ∼30  nm, respectively. Our result provides a new platform for the study of 2D superconductivity at oxide interfaces.
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http://dx.doi.org/10.1103/PhysRevLett.126.026802DOI Listing
January 2021

Probing the Intracellular Dynamics of Nitric Oxide and Hydrogen Sulfide Using an Activatable NIR II Fluorescence Reporter.

Angew Chem Int Ed Engl 2021 04 3;60(15):8450-8454. Epub 2021 Mar 3.

Key Laboratory for Advanced Materials, Institute of Fine Chemicals, School of Chemistry and Molecular Engineering, Frontiers Science Center for Materiobiology and Dynamic Chemistry, East China University of Science and Technology, Shanghai, 200237, P. R. China.

Understanding the complex interplay among gasotransmitters is of great significance but remains technically challenging. In this study, we present the design and synthesis of a dually responsive BOD-NH-SC reporter for probing the dynamic and alternating existence of NO and H S in living cells. This designed reporter can repeatedly cycle S-nitrosation and transnitrosation reactions when successively treated with NO and H S, thus affording the interchange of NIR fluorescence at 645 nm (NO) and NIR II fluorescence at 936 nm (H S). In light of this unique fluorescence alternation between two colors, we synthesized water-soluble BOD-NH-SC dots to visualize the intracellular dynamics of NO and H S. These molecular probes thus provide a toolbox to elucidate the interplaying roles of NO and H S in the complex interaction networks of various signal transduction pathways.
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http://dx.doi.org/10.1002/anie.202015650DOI Listing
April 2021

The therapeutic significance of the novel photodynamic material TPE-IQ-2O in tumors.

Aging (Albany NY) 2020 12 19;13(1):1383-1409. Epub 2020 Dec 19.

Department of Thoracic Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.

Combination therapies based on photodynamic therapy (PDT) have received much attention in various cancers due to their strong therapeutic effects. Here, we aimed to explore the safety and effectiveness of a new mitochondria-targeting photodynamic material, TPE-IQ-2O, in combination therapies (combined with surgery or immunotherapy). The safety and effectiveness of TPE-IQ-2O PDT were verified with cytotoxicity evaluation and a zebrafish xenograft model , respectively. The effectiveness of TPE-IQ-2O PDT combined with surgery or immune checkpoint inhibitors (ICIs) was verified in tumor-bearing mice. Small animal imaging, immunohistochemistry, and flow cytometry were used to determine the underlying mechanism. TPE-IQ-2O PDT can not only reduce tumor recurrence in surgical treatment but also effectively improve the response to ICIs in immunotherapy without obvious toxicity. It was also found to ameliorate the immunosuppressive tumor microenvironment and promote the antitumor immunity induced by ICIs by increasing CD8 tumor-infiltrating lymphocyte accumulation. Thus, TPE-IQ-2O PDT is a safe and effective antitumor therapy that can be combined with surgery or immunotherapy.
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http://dx.doi.org/10.18632/aging.202355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835032PMC
December 2020

Memory-Augmented Capsule Network for Adaptable Lung Nodule Classification.

IEEE Trans Med Imaging 2021 Jan 12;PP. Epub 2021 Jan 12.

Computer-aided diagnosis (CAD) systems must constantly cope with the perpetual changes in data distribution caused by different sensing technologies, imaging protocols, and patient populations. Adapting these systems to new domains often requires significant amounts of labeled data for re-training. This process is labor-intensive and time-consuming. We propose a memory-augmented capsule network for the rapid adaptation of CAD models to new domains. It consists of a capsule network that is meant to extract feature embeddings from some high-dimensional input, and a memory-augmented task network meant to exploit its stored knowledge from the target domains. Our network is able to efficiently adapt to unseen domains using only a few annotated samples. We evaluate our method using a large-scale public lung nodule dataset (LUNA), coupled with our own collected lung nodules and incidental lung nodules datasets. When trained on the LUNA dataset, our network requires only 30 additional samples from our collected lung nodule and incidental lung nodule datasets to achieve clinically relevant performance (0.925 and 0.891 area under receiving operating characteristic curves (AUROC), respectively). This result is equivalent to using two orders of magnitude less labeled training data while achieving the same performance. We further evaluate our method by introducing heavy noise, artifacts, and adversarial attacks. Under these severe conditions, our network's AUROC remains above 0.7 while the performance of state-of-the-art approaches reduce to chance level.
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http://dx.doi.org/10.1109/TMI.2021.3051089DOI Listing
January 2021

Deferasirox (ExJade): An FDA-Approved AIEgen Platform with Unique Photophysical Properties.

J Am Chem Soc 2021 01 11;143(3):1278-1283. Epub 2021 Jan 11.

Department of Chemistry, The University of Texas at Austin, 105 East 24th Street-A5300, Austin, Texas 78712-1224, United States.

Deferasirox, ExJade, is an FDA-approved iron chelator used for the treatment of iron overload. In this work, we report several fluorescent deferasirox derivatives that display unique photophysical properties, i.e., aggregation-induced emission (AIE), excited state intramolecular proton transfer, charge transfer, and through-bond and through-space conjugation characteristics in aqueous media. Functionalization of the phenol units on the deferasirox scaffold afforded the fluorescent responsive pro-chelator ExPhos, which enabled the detection of the disease-based biomarker alkaline phosphatase (ALP). The diagnostic potential of these deferasirox derivatives was supported by bacterial biofilm studies.
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http://dx.doi.org/10.1021/jacs.0c11641DOI Listing
January 2021

The "floating ulna" injury in adults: a case report, literature review and proposed injury classification.

BMC Musculoskelet Disord 2021 Jan 6;22(1):20. Epub 2021 Jan 6.

Department of Orthopedics Surgery, Yantai Yuhuangding Hospital Affiliated to Medical College of Qingdao University, 20 East Yuhuangding Rd, Zhifu District, Yantai, 264400, Shandong, P. R. China.

Background: Ipsilateral Galeazzi fracture with elbow dislocation, namely the "floating ulna" injury, is a rare injury pattern. A few reports have described this type of injury and its treatment.

Case Presentation: A 33-year-old female at 38 weeks gestational age presented with Galeazzi fracture and posterolateral elbow dislocation of the left upper extremity. The patient was treated with closed reduction of the elbow, open reduction, and internal fixation of the radial shaft fracture with a dynamic compression plate and K-wire stabilization of the unstable distal radioulnar joint. At the 12-month follow-up, the patient had no pain or signs of instability. Range of motion was 0-135° at the elbow, 70° extension and 80° flexion at the wrist, and 80° supination and 80° pronation at the forearm.

Conclusion: The "floating ulna" injury is a rare and special injury pattern with ipsilateral Galeazzi fracture and elbow dislocation. This type of injury was likely caused by significant amount of deforming force and the unique position of upper limb when the patient fell from a height of 1-2 m in high-energy trauma.
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http://dx.doi.org/10.1186/s12891-020-03880-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786482PMC
January 2021