Publications by authors named "Weipeng Wang"

84 Publications

The Regulatory Role of PRRX1 in Cancer Epithelial-Mesenchymal Transition.

Onco Targets Ther 2021 16;14:4223-4229. Epub 2021 Jul 16.

Institute of Medical Biotechnology, Suzhou Vocational Health College, Suzhou, Jiangsu, 215009, People's Republic of China.

PRRX1 (paired related homeobox 1), a member of the paired homeobox family, exhibits an important role in tumor. It is closely correlated to the occurrence of epithelial-mesenchymal transition (EMT). PRRX1 is an important transcription factor regulating EMT and plays an important role in tumor progression. In the process of tumor metastasis, PRRX1 mainly regulates the occurrence of EMT in tumor cells through TGF-β signaling pathway, Wnt/β-catenin signaling pathway and Notch signaling pathway. PRRX1 is not only closely related to the tumor cell stemness but also involved in miRNA regulation of EMT. Therefore, PRRX1 may be a target for inhibiting the proliferation, metastasis and stemness of tumor cells. The current review provides a systemic profile of the regulatory role of PRRX1 in cancer epithelial-mesenchymal transition.
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http://dx.doi.org/10.2147/OTT.S316102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8291965PMC
July 2021

Fish oil-based lipid emulsion alleviates parenteral nutrition-associated liver diseases and intestinal injury in piglets.

JPEN J Parenter Enteral Nutr 2021 Jul 21. Epub 2021 Jul 21.

Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Background: Thisstudy aimed to investigate the impact of fish oil-based lipid emulsion (FO) on enterohepatic injuries and intestinal microbiota in piglets of parenteral nutrition (PN).

Methods: Newborn piglets were divided into three groups, including enteral diet (the controls), PN with 100% FO and PN with medium-chain triglyceride/long-chain triglyceride-based lipid emulsion (MCT/LCT) for 14 days. Serum biochemical indicators, hepatic and intestinal histology, and expression of genes associated with inflammation, oxidative stress, and lipid metabolism were measured. The bile acid (BA) profiles in serum and the taxonomic composition of the gut microbiome in different intestinal segments were analyzed.

Results: Compared with MCT/LCT-piglets, FO reduced inflammation, promoted fatty acid oxidation, and decreased oxidative stress in the liver. In the intestine, FO decreased intestinal inflammation and intestinal permeability, leading to reduced lipopolysaccharide entry into the blood circulation relative to MCT/LCT-piglets. PN groups have dominant contents of Proteobacteria and Bacteroides, whereas the control group have Firmicutes at the phylum level. FO altered the taxonomic compositions of the gut microbiome in different segments, increased the relative abundance of Bacteroidaceae in ileum, and Rikenellaceae and Ruminococcaceae in the colon. FO treatment shifted BA composition ratio in serum and had a lower ratio of secondary BAs to primary BAs.

Conclusion: FO alleviates PNLAD and intestinal injury by regulating the homeostasis of BAs' enterohepatic circulation and altering microbiota composition in different intestinal segments.
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http://dx.doi.org/10.1002/jpen.2229DOI Listing
July 2021

Comparative Study of Oral Bacteria and Fungi Microbiota in Tibetan and Chinese Han Living at Different Altitude.

Tohoku J Exp Med 2021 06;254(2):129-139

West China School of Public Health and West China Fourth Hospital, Sichuan University.

Knowledge about the impact of altitude and ethnicity on human oral microbiota is currently limited. To obtain the baseline of normal salivary microbiota, we analyzed the bacteria and fungi composition in Tibetan (HY group) and Han population (CD group) living at different altitudes by using next-generation sequencing (NGS) technology combined with PICRUSt and FUNGuild analyses. There were significant differences in oral microbiota composition between the two groups at phylum and genus levels. At the phylum level, the HY group had higher relative abundances of Firmicutes and Ascomycota, whereas the Bacteroidetes and Basidiomycota in the CD group were richer. These changes at the phylum level reflected different dominant genus compositions. Compared with the Han population, Candida, Fusarium, Zopfiella, Streptococcus, Veillonella and Rothia in Tibetan were higher. Surprisingly, the Zopfiella was found almost exclusively in the Tibetan. The PICRUSt and FUNGuild analysis also indicated that the function of the bacterial and fungal communities was altered between the two groups. In conclusion, our results suggest that there are significant differences in oral microbial structure and metabolic characteristics and trophic modes among Tibetan and Han population living at different altitudes. We first established the oral microbiota framework and represented a critical step for determining the diversity of oral microbiota in the Tibetan and Han population.
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http://dx.doi.org/10.1620/tjem.254.129DOI Listing
June 2021

Conditional depletion of macrophages ameliorates cholestatic liver injury and fibrosis via lncRNA-H19.

Cell Death Dis 2021 06 24;12(7):646. Epub 2021 Jun 24.

Division of Pediatric Gastroenterology and Nutrition, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Although macrophages are recognized as important players in the pathogenesis of chronic liver diseases, their roles in cholestatic liver fibrosis remain incompletely understood. We previously reported that long noncoding RNA-H19 (lncRNA-H19) contributes to cholangiocyte proliferation and cholestatic liver fibrosis of biliary atresia (BA). We here show that monocyte/macrophage CD11B mRNA levels are increased significantly in livers of BA patients and positively correlated with the progression of liver inflammation and fibrosis. The macrophages increasingly infiltrate and accumulate in the fibrotic niche and peribiliary areas in livers of BA patients. Selective depletion of macrophages using the transgenic CD11b-diphtheria toxin receptor (CD11b-DTR) mice halts bile duct ligation (BDL)-induced progression of liver damage and fibrosis. Meanwhile, macrophage depletion significantly reduces the BDL-induced hepatic lncRNA-H19. Overexpression of H19 in livers using adeno-associated virus serotype 9 (AAV9) counteracts the effects of macrophage depletion on liver fibrosis and cholangiocyte proliferation. Additionally, both H19 knockout (H19) and conditional deletion of H19 in macrophage (H19) significantly depress the macrophage polarization and recruitment. lncRNA-H19 overexpressed in THP-1 macrophages enhance expression of Rho-GTPase CDC42 and RhoA. In conclusions, selectively depletion of macrophages suppresses cholestatic liver injuries and fibrosis via the lncRNA-H19 and represents a potential therapeutic strategy for rapid liver fibrosis in BA patients.
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http://dx.doi.org/10.1038/s41419-021-03931-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225916PMC
June 2021

Enhanced Valley Polarization of Bilayer MoSe with Variable Stacking Order and Interlayer Coupling.

J Phys Chem Lett 2021 Jul 18;12(25):5879-5888. Epub 2021 Jun 18.

Department of Physics, Beijing Normal University, Beijing 100875, P. R. China.

In two-dimensional transitional metal dichalcogenides, tuning the spin-valley-layer coupling via changing layer numbers and stacking orders remains desirable for their application in valleytronics. Herein, six-point star-like MoSe nanoflakes simultaneously containing different atom registration regions from monolayer to bilayer with 2H and 3R stacking order were fabricated, and the valley polarizations were comparably investigated by circular polarized photoluminescent spectroscopy. The degree of valley polarization was detected to be about 12.5% in the monolayer and 10% in the 2H bilayer, but greatly upgraded to about 40% in the 3R bilayer MoSe. This enhancement was attributed to the multiband spin splitting and generation of spin-dependent layer polarization for the 3R MoSe bilayer, which is well evidenced by our calculations of the energy band structures. Our results demonstrate that preparing TMD crystals with controllable stacking orders and interlayer coupling is a promising route to tune the valley index in TMDs for developing valleytronics technology.
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http://dx.doi.org/10.1021/acs.jpclett.1c01578DOI Listing
July 2021

Concomitant inhibition of B7-H3 and PD-L1 expression by a novel and synthetic microRNA delivers potent antitumor activities in colorectal tumor models.

Invest New Drugs 2021 Oct 28;39(5):1267-1274. Epub 2021 Apr 28.

College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China.

The families of miR-34 and miR-449 share the same seed region. However, the members showed differential effects on the expression of B7-H3 and PD-L1 in HCT-116 cells. Using miR-34a as a template, the non-seed region was modified by nucleotide alteration, yielding four synthetic microRNA (miRNA) analogs. Among those, NS-MX3, with a base alteration from G to C at the 18th locus of miR-34a, showed the most potent inhibition on both B7-H3 and PD-L1 expression. Subsequent investigations demonstrated that NS-MX3 had a broad anti-proliferation activity against several colorectal tumor cell lines and its antitumor effect was consistently reflected by tumor growth inhibition (TGI) in the HCT-116 xenograft model. In addition, NS-MX3 displayed a synergistic effect on TGI when combined with bevacizumab or regorafenib. Further analysis revealed that the superior antitumor activity of NS-MX3 was correlated to concomitant suppression of both B7-H3 and PD-L1 expression in tumor tissues. Taken together, the present study indicates that the non-seed region of miRNAs plays an important role in the regulation of checkpoint genes, thus showcasing single nucleotide alteration of the non-seed region as a promising approach to discover and develop novel immunotherapies.
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http://dx.doi.org/10.1007/s10637-021-01123-4DOI Listing
October 2021

A nonbile acid farnesoid X receptor agonist tropifexor potently inhibits cholestatic liver injury and fibrosis by modulating the gut-liver axis.

Liver Int 2021 09 18;41(9):2117-2131. Epub 2021 May 18.

Division of Pediatric Gastroenterology and Nutrition, Xin Hua hosiptal, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Background & Aims: Tropifexor (TXR) is a novel nonbile acid that acts as an agonist of farnesoid X receptor (FXR). TXR is currently in Phase 2 trials for the treatment of non-alcoholic steatohepatitis (NASH). Herein, we report the impact of TXR on in a piglet model in which cholestatic liver damage and fibrosis where induced by bile duct ligation (BDL).

Methods: The piglets received BDL and TXR for 2 wk. Hepatic, portal and colonic bile acid and amino acid profiles and gut microbiome were analysed. Portal fibroblast growth factor (FGF) 19 levels were measured using an enzyme-linked immunosorbent assay (ELISA).

Results: We first showed that bile acid metabolism and signalling are dysfunctional in patients with biliary atresia. Next, we observed that TXR potently suppresses BDL-induced liver injury, fibrosis and ductular reaction in piglets. Within the ileum, TXR enhances FGF19 expression and subsequently increases portal FGF19 levels. In the liver, TXR promotes the expression of small heterodimer partner (SHP) and inhibits cholesterol 7α-hydroxylase (CYP7A1). Additionally, TXR increases the abundance of bile acid-biotransforming bacteria in the distal ileum and alters the composition of amino acids in the colon. Lastly, TXR ameliorates intestinal barrier injury in piglets subjected to BDL.

Conclusion: TXR potently ameliorated cholestatic liver injury and fibrosis by modulating the gut-liver axis in piglets. It supports the clinical evaluation of TXR as a therapeutic strategy for cholestatic liver diseases, such as biliary atresia.
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http://dx.doi.org/10.1111/liv.14906DOI Listing
September 2021

Os Doping Suppressed Cu-Fe Charge Transfer and Induced Structural and Magnetic Phase Transitions in LaCuFeOsO ( = 1 and 2).

Inorg Chem 2021 May 13;60(9):6298-6305. Epub 2021 Apr 13.

Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100190, China.

B-site Os-doped quadruple perovskite oxides LaCuFeOsO ( = 1 and 2) were prepared under high-pressure and high-temperature conditions. Although parent compound LaCuFeO experiences Cu-Fe intermetallic charge transfer that changes the Cu/Fe charge combination to Cu/Fe at 393 K, in the Os-doped samples, the Cu and Fe charge states are found to be constant 2+ and 3+, respectively, indicating the complete suppression of charge transfer. Correspondingly, Os and mixed Os valence states are determined by X-ray absorption spectroscopy for = 1 and = 2 compositions, respectively. The = 1 sample crystallizes in an Fe/Os disordered structure with the 3̅ space group. It experiences a spin-glass transition around 480 K. With further Os substitution up to = 2, the crystal symmetry changes to 3̅, where Fe and Os are orderly distributed in a rocksalt-type fashion at the B site. Moreover, this composition shows a long-range Cu(↑)Fe(↑)Os(↓) ferrimagnetic ordering near 520 K. This work provides a rare example for 5d substitution-suppressed intermetallic charge transfer as well as induced structural and magnetic phase transitions with high spin ordering temperature.
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http://dx.doi.org/10.1021/acs.inorgchem.1c00009DOI Listing
May 2021

The Farnesoid X Receptor Agonist Tropifexor Prevents Liver Damage in Parenteral Nutrition-fed Neonatal Piglets.

J Pediatr Gastroenterol Nutr 2021 07;73(1):e11-e19

Department of Pediatric Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University.

Objectives: Intestinal failure-associated liver disease (IFALD) is a life-threatening complication for patients with intestinal failure who receive long-term parenteral nutrition (PN). We evaluated the effects of the farnesoid X receptor agonist tropifexor on a neonatal piglet model of IFALD fed with PN.

Methods: The piglets received PN and tropifexor for 14 days, then levels of liver enzymes, bile acid metabolism, inflammation, and intestinal barrier markers were assessed using quantitative real-time PCR. Fibroblast growth factor (FGF) 19 serum levels were determined using enzyme-linked immunosorbent assays. Bile acids were determined in liver, serum, and intestinal contents, and the microbiome was sequenced in different intestinal segments.

Results: The PN model was established in newborn piglets. The levels of serum liver enzymes, pro-inflammatory factors, and oxidative stress increased in the livers of piglets fed with PN, but not in those fed with PN and tropifexor. Tropifexor stimulated FGF19 expression in ileal epithelial cells, increased portal FGF19 levels, then inhibited cholesterol 7α-hydroxylase expression in the liver. Tropifexor increased the relative abundance of bacteria associated with bile salt hydrolase and 7α-dehydrogenation in the contents of ileum and altered the composition of bile acids in serum, liver, and intestinal contents. Tropifexor also inhibited intestinal inflammation, alleviated intestinal mucosal atrophy, and improved the intestinal barrier.

Conclusions: Tropifexor might prevent liver damage in neonatal piglets receiving PN by altering the composition of intestinal microbiota and bile acids. Tropifexor also alleviates intestinal inflammation and preserves the intestinal barrier.
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http://dx.doi.org/10.1097/MPG.0000000000003135DOI Listing
July 2021

Structure of human Na1.5 reveals the fast inactivation-related segments as a mutational hotspot for the long QT syndrome.

Proc Natl Acad Sci U S A 2021 03;118(11)

Department of Molecular Biology, Princeton University, Princeton, NJ 08544

Na1.5 is the primary voltage-gated Na (Na) channel in the heart. Mutations of Na1.5 are associated with various cardiac disorders exemplified by the type 3 long QT syndrome (LQT3) and Brugada syndrome (BrS). E1784K is a common mutation that has been found in both LQT3 and BrS patients. Here we present the cryo-EM structure of the human Na1.5-E1784K variant at an overall resolution of 3.3 Å. The structure is nearly identical to that of the wild-type human Na1.5 bound to quinidine. Structural mapping of 91- and 178-point mutations that are respectively associated with LQT3 and BrS reveals a unique distribution pattern for LQT3 mutations. Whereas the BrS mutations spread evenly on the structure, LQT3 mutations are clustered mainly to the segments in repeats III and IV that are involved in gating, voltage-sensing, and particularly inactivation. A mutational hotspot involving the fast inactivation segments is identified and can be mechanistically interpreted by our "door wedge" model for fast inactivation. The structural analysis presented here, with a focus on the impact of mutations on inactivation and late sodium current, establishes a structure-function relationship for the mechanistic understanding of Na1.5 channelopathies.
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http://dx.doi.org/10.1073/pnas.2100069118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7980460PMC
March 2021

miR-34a induces immunosuppression in colorectal carcinoma through modulating a SIRT1/NF-κB/B7-H3/TNF-α axis.

Cancer Immunol Immunother 2021 Aug 25;70(8):2247-2259. Epub 2021 Jan 25.

Center for Drug Metabolism and Pharmacokinetics, College of Pharmaceutical Sciences, Soochow University, Yunxuan Building #1339, Wenjing Road, Suzhou Industrial Park, Suzhou, 215123, China.

Although a number of studies have revealed the important roles of miR-34a in cancer, the regulatory roles of miR-34a in cancer immune response remain largely unknown. Our present study demonstrated a mechanism underlying miR-34a-mediated cancer immune evasion via a SIRT1/NF-κB/B7-H3/TNF-α axis. miR-34a upregulated B7-H3, an important immune checkpoint molecule, through direct inhibition of SIRT1 and consequent acetylation of NF-κB subunit p65 (a-p65), which promoted B7-H3 transcription by direct binding to its promoter. The elevated B7-H3 induced production of pro-inflammatory cytokines including TNF-α. This was further confirmed in the colon of Mir34a-deficient mice, where Sirt1 expression was boosted, and the expressions of a-p65, B7h3, and Tnf were repressed. Consequently, the in vivo inhibitory activity of miR-34a on colorectal cancer (CRC) was eradicated by the reinforced B7-H3 and TNF-α. In conclusion, our study uncovered an etiological mechanism underlying miR-34a-mediated CRC immune evasion through inhibition of SIRT1 and promotion of NF-κB/B7-H3/TNF-α axis.
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http://dx.doi.org/10.1007/s00262-021-02862-2DOI Listing
August 2021

Laparoscopic-Assisted Longitudinal Incision and Transverse Anastomosis: A Novel Surgical Approach for Treatment of Esophageal Stenosis Caused by Tracheobronchial Remnants.

J Laparoendosc Adv Surg Tech A 2021 Mar 5;31(3):343-347. Epub 2021 Jan 5.

Department of Pediatric Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

To review the treatment of lower congenital esophageal stenosis caused by tracheobronchial remnants (TBR) and to introduce a novel technical approach through laparoscopic surgery. Patients with TBR who underwent surgery in our single-center from January 2016 to December 2019 were enrolled. Resection of cartilage with stenotic esophageal segment and end-to-end anastomosis was the traditional surgery. Since 2018, longitudinal incision with partial resection of cartilage loop in the anterior esophageal wall and the transverse suture was conducted endoscopically. We reviewed the treatment, followed-up with these patients, and discussed the new procedure's preponderance. Thirteen patients underwent surgery and were followed-up for 0.5-45 months ( = 13) after surgery. Twelve patients showed good physical development with a regular diet. One patient, who was 2 weeks after the surgery, was fed by a soft diet and regularly followed-up at our clinic. In 13 cases, five patients underwent traditional laparotomy with pyloroplasty. Two patients who went through anastomotic leakage were cured by drainage and conservative treatments. Anastomotic stricture that occurred in two cases was improved by one-time of dilation. The administration time of parenteral nutrition (PN) was 9.0 ± 1.4 days. The length of hospitalization was 36.6 ± 5.2 days. Eight cases underwent the new surgical approach through laparoscopy or thoracoscopy. Pyloroplasty was avoided since the vagal close to the posterior wall of the esophagus was protected. Gastric motility disorder did not occur as expected. No leakage occurred postoperatively. The anastomotic stricture was found in six cases and improved after one to five times of dilations. The length of hospitalization dropped to 18.6 ± 6.9 days significantly ( < .001). Longitudinal incision and transverse anastomosis of the anterior wall of the esophagus with partial resection of cartilage without pyloroplasty through endoscopy is a novel practical surgical approach to treat patients with TBR.
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http://dx.doi.org/10.1089/lap.2020.0644DOI Listing
March 2021

Clay nanosheet-mediated delivery of recombinant plasmids expressing artificial miRNAs via leaf spray to prevent infection by plant DNA viruses.

Hortic Res 2020 Nov 1;7(1):179. Epub 2020 Nov 1.

Postdoctoral Research Base, Henan Institute of Science and Technology, Xinxiang, China.

Whitefly-transmitted begomoviruses are economically important plant pathogens that cause severe problems in many crop plants, such as tomato, papaya, cotton, and tobacco. Tomato yellow leaf curl virus (TYLCV) is a typical monopartite begomovirus that has been extensively studied, but methods that can efficiently control begomoviruses are still scarce. In this study, we combined artificial microRNA (amiRNA)-mediated silencing technology and clay nanosheet-mediated delivery by spraying and developed a method for efficiently preventing TYLCV infection in tomato plants. We designed three amiRNAs that target different regions of TYLCV to silence virus-produced transcripts. Three plant expression vectors expressing pre-amiRNAs were constructed, and recombinant plasmid DNAs (pDNAs) were loaded onto nontoxic and degradable layered double hydroxide (LDH) clay nanosheets. LDH nanosheets containing multiple pDNAs were sprayed onto plant leaves. We found that the designed amiRNAs were significantly accumulated in leaves 7 days after spraying, while the pDNAs were sustainably detected for 35 days after the spray, suggesting that the LDH nanosheets released pDNAs in a sustained manner, protected pDNAs from degradation and efficiently delivered pDNAs into plant cells. Importantly, when the LDH nanosheets coated with pDNAs were sprayed onto plants infected by TYLCV, both the disease severity and TYLCV viral concentration in sprayed plants were significantly decreased during the 35 days, while the levels of HO were significantly increased in those plants. Taken together, these results indicate that LDH nanosheets loaded with pDNAs expressing amiRNAs can be a sustainable and promising tool for begomovirus control.
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http://dx.doi.org/10.1038/s41438-020-00400-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603507PMC
November 2020

Publisher Correction: Multifunctional nanocoated membranes for high-rate electrothermal desalination of hypersaline waters.

Nat Nanotechnol 2020 Dec;15(12):1065

Department of Civil and Environmental Engineering, Rice University, Houston, TX, USA.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41565-020-00806-yDOI Listing
December 2020

Multifunctional nanocoated membranes for high-rate electrothermal desalination of hypersaline waters.

Nat Nanotechnol 2020 12 26;15(12):1025-1032. Epub 2020 Oct 26.

Department of Civil and Environmental Engineering, Rice University, Houston, TX, USA.

Surface heating membrane distillation overcomes several limitations inherent in conventional membrane distillation technology. Here we report a successful effort to grow in situ a hexagonal boron nitride (hBN) nanocoating on a stainless-steel wire cloth (hBN-SSWC), and its application as a scalable electrothermal heating material in surface heating membrane distillation. The novel hBN-SSWC provides superior vapour permeability, thermal conductivity, electrical insulation and anticorrosion properties, all of which are critical for the long-term surface heating membrane distillation performance, particularly with hypersaline solutions. By simply attaching hBN-SSWC to a commercial membrane and providing power with an a.c. supply at household frequency, we demonstrate that hBN-SSWC is able to support an ultrahigh power intensity (50 kW m) to desalinate hypersaline solutions with exceptionally high water flux (and throughput), single-pass water recovery and heat utilization efficiency while maintaining excellent material stability. We also demonstrate the exceptional performance of hBN-SSWC in a scalable and compact spiral-wound electrothermal membrane distillation module.
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http://dx.doi.org/10.1038/s41565-020-00777-0DOI Listing
December 2020

Robust quantitative SERS analysis with Relative Raman scattering intensities.

Talanta 2021 Jan 30;221:121465. Epub 2020 Jul 30.

Key Laboratory of Advanced Materials (MOE), School of Materials Science and Engineering, Tsinghua University, Beijing, 100084, China. Electronic address:

Robust quantitative analysis methods are very attractive but challenging with surface-enhanced Raman scattering (SERS) technique till now. Quantitative analysis methods using absolute Raman scattering intensities tend to desire very critical reproducibility of SERS substrates and consistency of testing conditions, as batch differences and inhomogeneity of SERS substrates as well as the fluctuation of measuring parameters placed challenging obstacles. Relative Raman scattering intensities, on the other hand, can release the adverse interferences mentioned above and provide effective and robust information as it is independent of the reproducibility of SERS substrates. By establishing external calibration working curves, we achieved accurate molecule composition prediction of molecules in multi-component systems. Further, by choosing or adding a label molecule with known concentration as Raman internal standards, the concentration of target molecules can be easily predicted. This approach proved the effectiveness and robustness of quantitative analysis with the relative Raman scattering intensities, even carried out with a flexible inhomogeneous SERS substrate.
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http://dx.doi.org/10.1016/j.talanta.2020.121465DOI Listing
January 2021

Functional Characterization Reveals the Significance of Rare Coding Variations in Human Organic Anion Transporting Polypeptide 2B1 (21).

Mol Pharm 2020 10 18;17(10):3966-3978. Epub 2020 Sep 18.

College of Pharmaceutical Sciences, Soochow University, 199 Renai Road, Suzhou Industrial Park, Suzhou 215123, China.

The organic anion transporting polypeptide 2B1 (OATP2B1), which is encoded by the 21 gene, plays important roles in the absorption and disposition of its substrate drugs. Nonsynonymous variations of 21 change its amino acid sequence and may alter its function. However, so far, very few genetic variants of 21 have been functionally characterized. In the present study, first of all, 14 nonsynonymous single nucleotide variants (SNVs) of 21 have been identified from the dbSNP database. Then, human embryonic kidney (HEK293) cells were employed as the expression system and functional studies were carried out for these 14 SNVs using substrates 4',5'-dibromofluorescein (DBF), estrone-3-sulfate (E3S), atorvastatin, and rosuvastatin. Our results showed that four nonsynonymous rare variants, namely, 21 c.332G > A (p.R111Q), c.1184C > A (p.P395H), c.1624G > A (p.V542M), and c.1998C > A (p.F666L), have great effect on the function of OATP2B1. Surface biotinylation and immunoblot analysis indicated that the variant c.1184C > A (p.P395H) almost completely disrupted OATP2B1's expression on the plasma membrane. According to the three-dimensional structural model of OATP2B1 we developed, these four mutated residues are not located at the substrate binding region of OATP2B1. Their significant effect on the function of OATP2B1 could probably be attributed to jeopardizing OATP2B1's surface expression as exemplified by c.1184C > A (p.P395H), altering the transporter's overall structure and affecting its interactions with other proteins or the lipid bilayer. Taken together, our results demonstrated that rare coding variants could have a great impact on the function and expression of OATP2B1.
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http://dx.doi.org/10.1021/acs.molpharmaceut.0c00747DOI Listing
October 2020

The rs7911488-T allele promotes the growth and metastasis of colorectal cancer through modulating miR-1307/PRRX1.

Cell Death Dis 2020 08 7;11(8):651. Epub 2020 Aug 7.

Center for Drug Metabolism and Pharmacokinetics, College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China.

We previously discovered that rs7911488T>C in pre-miR-1307 was closely correlated to the risk of colorectal cancer (CRC). However, the roles of rs7911488 in CRC are still largely unknown. Here we explored the roles of rs7911488 in the growth and metastasis of CRC. We firstly generated cell lines SW480-T and SW480-C for stable expression of rs7911488 T-allelic and C-allelic pre-miR-1307, respectively. We subcutaneously grafted the cells into nude mice. We found that SW480-T tumors with high expression of miR-1307 obviously grew faster than the SW480-C tumors. Moreover, liver metastases (5/8) were observed in the mice bearing SW480-T tumors but not the SW480-C tumor-bearing mice. The results from colony formation assays, transwell assays, and wound healing assays demonstrated that the proliferative and metastatic abilities of SW480-T cells were evidently more potent than the SW480-C cells. Then we utilized gene array, real-time PCR, western blotting, and dual-luciferase reporter assays to figure out that miR-1307 directly inhibited PPRX1 expression by binding to its 3'-UTR. Thereafter, we confirmed that the proliferative and metastatic abilities of SW480 and HCT-116 cells were markedly enhanced by miR-1307, but were suppressed by PRRX1. Moreover, the regulatory roles of miR-1307 in the proliferation and metastasis of CRC cells were reversed by PRRX1. Notably, we also found that PRRX1 repressed CRC tumor growth in nude mice. In summary, our current study revealed that rs7911488-T allele led to over-expression of miR-1307, which inhibited PRRX1 and consequently promoted the proliferation and migration of CRC cells. This might offer a novel insight into the progression of CRC.
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http://dx.doi.org/10.1038/s41419-020-02834-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7434880PMC
August 2020

High-Pressure Synthesis of a B-site Co/Mn Disordered Quadruple Perovskite LaMnCoMnO.

Inorg Chem 2020 Sep 12;59(17):12445-12452. Epub 2020 Aug 12.

Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100190, China.

A new oxide, LaMnCoMnO, was synthesized under high-pressure (7 GPa) and high-temperature (1423 K) conditions. The compound crystallizes in an AA'BO-type quadruple perovskite structure with space group 3̅. The Rietveld structural analysis combined with soft X-ray absorption spectroscopy reveals the charge combination to be LaMnCoMnO, where the La and Mn are 1:3 ordered respectively at the A and A' sites, whereas the Co and Mn are disorderly distributed at the B site. This is in sharp contrast to RCoMnO (R = La and rare earth) double perovskites, in which the Co and Mn charge states are always orderly distributed with a rocksalt-type fashion, giving rise to a long-range magnetic ordering. As a result, LaMnCoMnO displays spin glassy magnetic properties due to the random Co and Mn distribution, as demonstrated by dc and ac magnetic susceptibility as well as specific heat measurements. Possible factors that affect the B-site degree of order in perovskite structures are discussed.
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http://dx.doi.org/10.1021/acs.inorgchem.0c01548DOI Listing
September 2020

B7-H3 is spliced by SRSF3 in colorectal cancer.

Cancer Immunol Immunother 2021 Feb 27;70(2):311-321. Epub 2020 Jul 27.

Center for Drug Metabolism and Pharmacokinetics, College of Pharmaceutical Sciences, Soochow University, Building #1339, Wenjing Road, Suzhou Industrial Park, Suzhou, 215123, China.

B7-H3, an important co-inhibitor, is abnormally highly expressed in a variety of malignancies. The antibodies targeting B7-H3 have exhibited beneficial therapeutic effects in clinical trials. Therefore, discovery of the regulatory factors in B7-H3 expression may provide new strategies for tumor therapy. Here, we investigated the splicing factors involved in the splicing of B7-H3. By individual knockdown of the splicing factors in colorectal cancer (CRC) cells, we found that B7-H3 expression was markedly inhibited by SRSF3 and SRSF8, especially SRSF3. Then we found that both SRSF3 and B7-H3 were highly expressed in CRC tissues. Moreover, high-expression of either SRSF3 or B7-H3 was significantly correlated with poor prognosis of patients. The expression of B7-H3 mRNA and protein were evidently reduced by SRSF3 silence, but were enhanced by overexpression of SRSF3 in both HCT-116 and HCT-8 cells. The results from the RNA immunoprecipitation (RIP) assays demonstrated that SRSF3 protein directly binds to B7-H3 mRNA. In addition, we constructed a minigene recombinant plasmid for expressing B7-H3 exons 3-6. We found that SRSF3 contributed to the retention of B7-H3 exon 4. These findings demonstrate that SRSF3 involves in the splicing of B7-H3 by directly binding to its exon 4 and/or 6. It may provide novel insights into the regulatory mechanisms of B7-H3 expression and potential strategies for the treatment of CRC.
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http://dx.doi.org/10.1007/s00262-020-02683-9DOI Listing
February 2021

Chinese expert brief consensus on newborn screening of inherited metabolic disorders during the novel coronavirus infection epidemic.

Ann Transl Med 2020 Apr;8(7):429

Newborn Screening Center/Center for Clinical Molecular Laboratory Medicine, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.

Novel coronavirus (2019-nCov) infection (COVID-19) rapidly spread across China and 25 countries in the worldwide, which infected not only adults but also children, even neonates. Each year, about 15 million newborns are delivered in China. Newborn screening (NBS) helps effectively prevent some mental retardation, premature death, and adverse outcomes in the early stage of baby, which could detect some inherited metabolic disorders (IMDs). During this COVID-19 epidemic, how to balance the risk of infected 2019-nCov and the risk of disability and teratogenesis of IMDs. Expert members of NBS extra quality assessment in National Clinical Center of Laboratory (NCCL) give a brief consensus for NBS of IMDs in the COVID-2019 epidemic, hoping that the brief consensus could be reference for NBS of IMDs in the other epidemic areas or periods all over the world.
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http://dx.doi.org/10.21037/atm.2020.03.60DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7210144PMC
April 2020

Biomolecular sensing by surface-enhanced Raman scattering of monolayer Janus transition metal dichalcogenide.

Nanoscale 2020 May 9;12(19):10723-10729. Epub 2020 May 9.

Department of Materials Science and NanoEngineering, Rice University, 6100 Main Street, Houston, TX 77005, USA.

In this work, we demonstrate that monolayer Janus MoSSe is an effective and universal platform for enhancing Raman signal and detecting biomolecules for the first time. The out-of-plane dipoles in monolayer Janus MoSSe redistribute charges of adsorbed biomolecules, polarize biomolecules and enhance their Raman vibrational intensity. The estimated Raman enhancement factor is higher than 10, which is comparable with the highest reported enhancement factor for 2D substrates. The C-C stretching Raman peak around 1360 cm is used to indicate the glucose concentration, and its peak-integrated intensity increases linearly with the glucose concentration in the range of 1-10 mM. DFT calculations also confirm that charge redistribution in glucose induced by dipole interactions can enhance Raman intensity significantly when glucose molecules are adsorbed onto monolayer Janus MoSSe.
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http://dx.doi.org/10.1039/d0nr00300jDOI Listing
May 2020

A Low-Cost and High-Efficiency Integrated Device toward Solar-Driven Water Splitting.

ACS Nano 2020 May 4;14(5):5426-5434. Epub 2020 May 4.

Department of Materials Science and NanoEngineering, Rice University, 6100 Main Street, Houston, Texas 77005, United States.

Achieving the spontaneous evolution of fuel from integrated devices by solar-driven water splitting is an attractive method for renewable energy conversion. However, their widespread implementation is hindered by their immature architectures and inferior performances. Here, we propose a real integrated device consisting of two series-connected perovskite solar cells (PSCs) and two CoP catalyst electrodes, which can be immersed into the aqueous solution directly for solar-driven water splitting. Benefiting from the low-cost and facile encapsulation technique, this integrated device possesses a compact structure and well-connected circuits for the process of charge carriers generation, transfer, and storage. Moreover, although all expensive components in this integrated device are eliminated, the two series-connected carbon-based PSCs still exhibit a high solar-to-electric efficiency of 10.6% as well as the integrated devices display a solar-to-hydrogen efficiency of as high as 6.7%. This integrated device serves as a model architecture toward future development and optimization of the integrated device that can be immersed into the aqueous solution directly for water splitting.
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http://dx.doi.org/10.1021/acsnano.9b09053DOI Listing
May 2020

A Systemic Review on the Regulatory Roles of miR-34a in Gastrointestinal Cancer.

Onco Targets Ther 2020 3;13:2855-2872. Epub 2020 Apr 3.

Center for Drug Metabolism and Pharmacokinetics, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, People's Republic of China.

MicroRNAs (miRNAs) are a class of endogenous non-coding single-stranded small-molecule RNAs that regulate gene expression by repressing target messenger RNA (mRNA) translation or degrading mRNA. miR-34a is one of the most important miRNAs participating in various physiological and pathological processes. miR-34a is abnormally expressed in a variety of tumors. The roles of miR-34a in gastrointestinal cancer (GIC) draw lots of attention. Numerous studies have demonstrated that dysregulated miR-34a is closely related to the proliferation, differentiation, migration, and invasion of tumor cells, as well as the diagnosis, prognosis, treatment, and chemo-resistance of tumors. Thus, we systematically reviewed the abnormal expression and regulatory roles of miR-34a in GICs including esophageal cancer (EC), gastric cancer (GC), colorectal cancer (CRC), hepatocellular carcinoma (HCC), pancreatic cancer (PC), and gallbladder cancer (GBC). It may provide a profile of versatile roles of miR-34a in GICs.
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http://dx.doi.org/10.2147/OTT.S234549DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138617PMC
April 2020

VdTHI20, Involved in Pyrimidine Biosynthesis, Is Required for DNA Repair Functions and Pathogenicity.

Int J Mol Sci 2020 Feb 18;21(4). Epub 2020 Feb 18.

Henan Collaborative Innovation Center of Modern Biological Breeding, Henan Institute of Sciences and Technology, Xinxiang, Henan 453003, China.

() infects roots and colonizes the vascular vessels of host plants, significantly reducing the economic yield of cotton and other crops. In this study, the protein VdTHI20, which is involved in the thiamine biosynthesis pathway, was characterized by knocking out the corresponding gene in V. dahliae via -mediated transformation (ATMT). The deletion of VdTHI20 resulted in several phenotypic defects in vegetative growth and conidiation and in impaired virulence in tobacco seedlings. We show that VdTHI20 increases the tolerance of V. dahliae to UV damage. The impaired vegetative growth of ΔVdTHI20 mutant strains was restored by complementation with a functional copy of the VdTHI20 gene or by supplementation with additional thiamine. Furthermore, the root infection and colonization of the ΔVdTHI20 mutant strains were suppressed, as indicated by green fluorescent protein (GFP)-labelling under microscope observation. When the RNAi constructs of VdTHI20 were used to transform Nicotiana benthamiana, the transgenic lines expressing dsVdTHI20 showed elevated resistance to V. dahliae. Together, these results suggest that VdTHI20 plays a significant role in the pathogenicity of V. dahliae. In addition, the pathogenesis-related gene VdTHI20 exhibits potential for controlling V. dahliae in important crops.
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http://dx.doi.org/10.3390/ijms21041378DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073022PMC
February 2020

Host-induced gene silencing of the acetolactate synthases VdILV2 and VdILV6 confers resistance to Verticillium wilt in cotton (Gossypium hirsutum L.).

Biochem Biophys Res Commun 2020 04 29;524(2):392-397. Epub 2020 Jan 29.

Collaborative Innovation Center of Modern Biological Breeding of Henan Province, Henan Key Laboratory Molecular Ecology and Germplasm Innovation of Cotton and Wheat, School of Life Science and Technology, Henan Institute of Science and Technology, Henan, Xinxiang, 453003, China. Electronic address:

Cotton Verticillium wilt caused by Verticillium dahliae (V. dahliae) is one of the most destructive fungal diseases and is difficult to control. However, resistant germplasm resources are scarce in cotton. Many studies have shown that host-induced gene silencing (HIGS) is a practical and effective technology in crop disease prevention by silencing virulence genes of pathogens. Acetolactate synthase (ALS) contains a catalytic subunit ILV2 and a regulatory subunit ILV6, which catalyzes the first common step reaction in branched-chain amino acid (BCAA) biosynthesis. We identified two acetolactate synthases, VdILV2 and VdILV6, which are homologs of ILV2 and ILV6, respectively, in Magnaporthe oryzae. To characterize the function of VdILV2 and VdILV6 in V. dahliae, we suppressed their expression in the strong pathogenic isolate Vd991 by using HIGS technology. VdILV2- or VdILV6-silenced V. dahliae had a dramatic reduction in pathogenicity. The results indicated that VdILV2 and VdILV6 are involved in the pathogenicity of V. dahliae. HIGS of VdILV2 or VdILV6 provides a novel fungicide target and an effective control to resist Verticillium wilt caused by V. dahliae.
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http://dx.doi.org/10.1016/j.bbrc.2020.01.126DOI Listing
April 2020

Can early surgery improve the outcome of patients with meconium peritonitis? A single-center experience over 16 years.

BMC Pediatr 2019 12 3;19(1):473. Epub 2019 Dec 3.

Department of Pediatric Surgery, Xinhua hospital; Shanghai Jiao Tong University School of Medicine, No. 1665, Kongjiang Road, Shanghai, 200092, China.

Background: In the last century, meconium peritonitis(MP)was once a highly fatal gastrointestinal. disease With the development of fetal radiological technology, abnormal signs, such as pseudocysts, can. be detected during the fetal period so that more patients can be diagnosed prenatally and receive surgery. in the early stage of life. The survival rate of MP has increased up to 80% in recent years. According to. a review of the treatment and outcomes of patients diagnosed with MP, we evaluated the influence of. early operation on survival rate and discussed the risk factors of prognosis.

Methods: We collected 79 cases of patients diagnosed with MP who were treated in our department. from October 2001 to December 2017. They were divided into 2 groups. Patients in group A were born. in our hospital. Patients in group B were born in a local hospital with suspicion of MP and then transferred. to our department.

Results: The birth weight (BW) and gestational age (GA) of patients were higher in group A than in. group B. There was no significant difference in the proportion of premature and low birth weight (LBW). patients between the two groups (p = 0.422, p = 0.970). Their age at the time of surgery was younger in. group A than in group B (1.4 ± 2.0 vs. 6.9 ± 14.9, p < 0.001). The overall survival rate of group A was higher. than that of group B (95.0% vs. 79.5%, p = 0.038). The prognosis of premature patients was worse than. that of full-term infants for both groups (p = 0.012).

Conclusions: Prematurity is a significant risk factor related to death for MP patients. The survival rate. of MP patients can be improved by early operation during the neonatal period.
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http://dx.doi.org/10.1186/s12887-019-1844-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889670PMC
December 2019

Near-Room-Temperature Ferrimagnetic Ordering in a B-Site-Disordered 3d-5d-Hybridized Quadruple Perovskite Oxide, CaCuMnOsO.

Inorg Chem 2019 Nov 8;58(22):15529-15535. Epub 2019 Nov 8.

Beijing National Laboratory for Condensed Matter Physics , Institute of Physics, Chinese Academy of Sciences , Beijing 100190 , China.

A new 3d-5d hybridization oxide, CaCuMnOsO (CCMOO), was prepared by high-pressure and high-temperature synthesis methods. The compound crystallizes to an A-site-ordered but B-site-disordered quadruple perovskite structure with a space group of 3̅ (No. 204). The charge states of the transition metals are determined to be Cu/Mn/Os by X-ray absorption spectroscopy. Although most B-site-disordered perovskites possess lower spin-ordering temperatures or even nonmagnetic transitions, the current CCMOO displays a long-range ferrimagnetic phase transition with a critical temperature as high as ∼280 K. Moreover, a large saturated magnetic moment is found to occur [7.8 μ/formula units (f.u.) at 2 K]. X-ray magnetic circular dichroism shows a Cu(↑)Mn(↑)Os(↓) ferrimagnetic coupling. The corner-sharing Mn/OsO octahedra with mixed Mn and Os charge states make the compound metallic in electrical transport, in agreement with a specific heat fitting at low temperature. This work provides a rare example with high spin-ordering temperature and a large magnetic moment in B-site-disordered 3d-5d hybridization perovskite oxides.
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http://dx.doi.org/10.1021/acs.inorgchem.9b02576DOI Listing
November 2019

High-pressure synthesis and spin glass behavior of a Mn/Ir disordered quadruple perovskite CaCuMnIrO.

J Phys Condens Matter 2020 Feb 1;32(7):075701. Epub 2019 Nov 1.

Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100190, People's Republic of China. School of Physical Sciences, University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China.

A new 3d-5d hybridized quadruple perovskite oxide, CaCuMnIrO, was synthesized by high-pressure and high-temperature methods. The Rietveld structure analysis reveals that the compound crystallizes in an [Formula: see text]-type perovskite structure with space group Im-3, where the Ca and Cu are 1:3 ordered at fixed atomic positions. At the B site the 3d Mn and the 5d Ir ions are disorderly distributed due to the rare equal  +4 charge states for both of them as determined by x-ray absorption spectroscopy. The competing antiferromagnetic and ferromagnetic interactions among Cu, Mn, and Ir ions give rise to spin glass behavior, which follows a conventional dynamical slowing down model.
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http://dx.doi.org/10.1088/1361-648X/ab5386DOI Listing
February 2020

Two Kinds of Metastable Structures in an Epitaxial Lanthanum Cobalt Oxide Thin Film.

Inorg Chem 2019 Oct 26;58(19):13440-13445. Epub 2019 Sep 26.

Beijing National Laboratory of Condensed Matter Physics , Institute of Physics, Chinese Academy of Sciences , Beijing 100190 , P. R. China.

Thin films have attracted much interest because they often have novel properties different from those of their bulk counterparts. In this work, we tune two metastable states in three kinds of lanthanum cobalt oxide thin films by electron beam irradiation and record their dynamic transition process in situ in a transmission electron microscope. The lanthanum cobalt oxide thin films exhibit a homogeneous microstructure in the initial state and then transfer to a stripelike superstructure with 3 periodicity ( is the perovskite lattice parameter), further developing into a superstructure with 2 periodicity in dark stripes (brownmillerite structure). To explore the inherent energy discrepancy within the two metastable states, we perform first-principles calculations on a LaCoO (0 ≤ δ ≤ 0.5) thin film system by geometry optimization. The calculation results suggest that the forming energy of the 3 periodicity stripelike structure is a little lower than that of the 2 periodicity in the LaCoO thin film. Our work explains why the two stripelike structures coexist in lanthanum cobalt oxide thin films and extends prospective applications related to oxygen vacancies in thin films.
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http://dx.doi.org/10.1021/acs.inorgchem.9b02326DOI Listing
October 2019
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