Publications by authors named "Wenbin Huang"

136 Publications

Correlation Between Circulating Tumor Cell DNA Genomic Alterations and Mesenchymal CTCs or CTC-Associated White Blood Cell Clusters in Hepatocellular Carcinoma.

Front Oncol 2021 11;11:686365. Epub 2021 Jun 11.

General Surgery Center, Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China.

Purpose: Liquid biopsy is attracting attention as a method of real-time monitoring of patients with tumors. It can be used to understand the temporal and spatial heterogeneity of tumors and has good clinical application prospects. We explored a new type of circulating tumor cell (CTC) enrichment technology combined with next-generation sequencing (NGS) to analyze the correlation between genomic alterations in circulating tumor cells of hepatocellular carcinoma and the counts of mesenchymal CTCs and CTC-associated white blood cell (CTC-WBC) clusters.

Methods: We collected peripheral blood samples from 29 patients with hepatocellular carcinoma from January 2016 to December 2019. We then used the CanPatrol™ system to capture and analyze mesenchymal CTCs and CTC-WBC clusters for all the patients. A customized Illumina panel was used for DNA sequencing and the Mann-Whitney U test was used to test the correlation between mesenchymal CTCs, CTC-WBC cluster counts, and specific genomic changes.

Results: At least one somatic hotspot mutation was detected in each of the 29 sequenced patients. A total of 42 somatic hot spot mutations were detected in tumor tissue DNA, and 39 mutations were detected in CTC-DNA, all of which included common changes in PTEN, MET, EGFR, RET, and FGFR3. The number of mesenchymal CTCs was positively correlated with the somatic genomic alterations in the PTEN and MET genes (PTEN, P = 0.021; MET, P  = 0.008, Mann-Whitney U test) and negatively correlated with the somatic genomic alterations in the EGFR gene (P = 0.006, Mann-Whitney U test). The number of CTC-WBC clusters was positively correlated with the somatic genomic alterations in RET genes (P  = 0.01, Mann-Whitney U test) and negatively correlated with the somatic genomic alterations in FGFR3 (P = 0.039, Mann-Whitney U test).

Conclusions: We report a novel method of a CTC enrichment platform combined with NGS technology to analyze genetic variation, which further demonstrates the potential clinical application of this method for spatiotemporal heterogeneity monitoring of hepatocellular carcinoma. We found that the number of peripheral blood mesenchymal CTCs and CTC-WBC clusters in patients with hepatocellular carcinoma was related to a specific genome profile.
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http://dx.doi.org/10.3389/fonc.2021.686365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226125PMC
June 2021

A Lamb waves based ultrasonic system for the simultaneous data communication, defect inspection, and power transmission.

IEEE Trans Ultrason Ferroelectr Freq Control 2021 Jun 8;PP. Epub 2021 Jun 8.

Lamb waves based structural health monitoring (SHM) has attracted extensive attention in recent years. This article aims to realize the functions of data communication, defect detection and energy transmission through piezoelectric transducers. In this work, the S0 mode at 500 kHz and A0 mode at 150 kHz are selected as the carrier waves and the optimized excitation frequencies are determined through analytical investigation and frequency sweeping experiments. S0 mode is used for data communication and defect inspection due to the high excitation frequency and low dispersion properties. A single piezoelectric sensing element acts as the transmitter and a nine-element piezoelectric transducer array is the receiver. Their roles exchanges in terms of the energy transmission based on the A0 mode. Simultaneous data communication and energy transmission are achieved based on the frequency division multiplexing (FDM) strategy. After performing a matched filter on the received signals, the digital data information can be recovered under the interference of the energy transmission signal. The synthetic aperture imaging technology (SAFT) is adopted for accurately locating defects on aluminum plates. In terms of energy transmission, a constructive interference performance is achieved by the transducer array with a transmitted power of 3.81 mW. This system has great potential for the health monitoring of the enclosed structure by eliminating the cumbersome wires for powering and communication.
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http://dx.doi.org/10.1109/TUFFC.2021.3087603DOI Listing
June 2021

Dapagliflozin Alleviates Hepatic Steatosis by Restoring Autophagy via the AMPK-mTOR Pathway.

Front Pharmacol 2021 17;12:589273. Epub 2021 May 17.

Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.

As a newly approved oral hypoglycaemic agent, the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin, which is derived from the natural product phlorizin can effectively reduce blood glucose. Recent clinical studies have found that dapagliflozin alleviates non-alcoholic fatty liver disease (NAFLD), but the specific mechanism remains to be explored. This study aimed to investigate the underlying mechanism of dapagliflozin in alleviating hepatocyte steatosis and . We fed the spontaneous type 2 diabetes mellitus rats with high-fat diets and cultured human normal liver LO2 cells and human hepatocellular carcinoma HepG2 cells with palmitic acid (PA) to induce hepatocellular steatosis. Dapagliflozin attenuated hepatic lipid accumulation both and . In Zucker diabetic fatty (ZDF) rats, dapagliflozin reduced hepatic lipid accumulation via promoting phosphorylation of acetyl-CoA carboxylase 1 (ACC1), and upregulating lipid -oxidation enzyme acyl-CoA oxidase 1 (ACOX1). Furthermore, dapagliflozin increased the expression of the autophagy-related markers LC3B and Beclin1, in parallel with a drop in p62 level. Similar effects were observed in PA-stimulated LO2 cells and HepG2 cells. Dapagliflozin treatment could also significantly activated AMPK and reduced the phosphorylation of mTOR in ZDF rats and PA-stimulated LO2 cells and HepG2 cells. We demonstrated that dapagliflozin ameliorates hepatic steatosis by decreasing lipogenic enzyme, while inducing fatty acid oxidation enzyme and autophagy, which could be associated with AMPK activation. Moreover, our results indicate that dapagliflozin induces autophagy via the AMPK-mTOR pathway. These findings reveal a novel clinical application and functional mechanism of dapagliflozin in the treatment of NAFLD.
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http://dx.doi.org/10.3389/fphar.2021.589273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176308PMC
May 2021

Functional identification of a rare vascular endothelial growth factor a () variant associating with the nonsyndromic cleft lip with/without cleft palate.

Bioengineered 2021 12;12(1):1471-1483

Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, China.

Vascular endothelial growth factor A (VEGFA) is a crucial growth factor, which participates in multiple processes of human growth and development, such as angiogenesis and osteogenesis and is also necessary for development of palate. The purpose of this study was to investigate the effect of a rare mutation (NM_001025366.2 773 T > C p.Val258Ala) on the cell functions and osteogenesis. Here, we found that the mutation has adverse effects on the function of human embryonic palatal plate mesenchymal (HEPM) cells, and may affect the development of palate. The mutation has adverse effects on promoting cell proliferation and migration and inhibiting apoptosis in HEPM and HEK-293 cells. In addition, the mutant allele has a negative influence on osteogenesis. Taken together, the rare variant of gene had an adverse effect on cell functions and osteogenesis, which may impact the development of the palate. And these findings suggested that mutation (c.773 T > C) may lead to nonsyndromic cleft lip with or without cleft palate and also provide a new insight into the mechanism of gene in osteogenesis and palatogenesis.
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http://dx.doi.org/10.1080/21655979.2021.1912547DOI Listing
December 2021

The anterior and posterior biometric characteristics in primary angle-closure disease: Data based on anterior segment optical coherence tomography and swept-source optical coherence tomography.

Indian J Ophthalmol 2021 04;69(4):865-870

Zhongshan Ophthalmic Center, State Key Laboratory of Ophthalmology, Sun Yat-Sen University, Guangzhou, People's Republic of China.

Purpose: Obtaining a better understanding of the pathogenesis of primary angle-closure disease (PACD) still requires studies that provide measurements of anterior and posterior biometric characteristics together and that assess the relationship between them.

Methods: In total, 201 eyes were enrolled in this cross-sectional study: 50 normal controls, 49 primary angle-closure suspect (PACS), 38 primary angle closure (PAC), and 64 primary angle-closure glaucoma (PACG) eyes. The anterior and posterior structural features were measured by anterior segment optical coherence tomography and swept-source optical coherence tomography.

Results: All PACD groups had smaller anterior chamber depth (ACD), anterior chamber area (ACA), anterior chamber volume (ACV), angle opening distance at 750 μm from the scleral spur (AOD750), trabecular-iris space area at 750 μm from the scleral spur (TISA750), and angle recess area (ARA), as well as a larger lens vault (LV), than controls (all P < 0.001). The PACS and PAC groups had thicker iris thickness at 750 μm from the scleral spur (IT750) than controls (P = 0.017 and P = 0.002, respectively). Choroidal thickness (CT) was not statistically different among normal, PACS, PAC, and PACG eyes. Univariate and multivariate linear regression analysis revealed a significant association between thinner IT750 and increased CT in PACD eyes (P = 0.031, univariate analysis; P = 0.008, multivariate analysis).

Conclusion: Thinner iris thickness was associated with increased CT in PACD eyes; however, the underlying mechanism needs further investigation.
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http://dx.doi.org/10.4103/ijo.IJO_936_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012975PMC
April 2021

Polyethylenimine quantity and molecular weight influence its adjuvanting properties in liposomal peptide vaccines.

Bioorg Med Chem Lett 2021 05 9;40:127920. Epub 2021 Mar 9.

School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia. Electronic address:

We recently reported that polyethylenimine (PEI; molecular weight of 600 Da) acted as a vaccine adjuvant for liposomal group A Streptococcus (GAS) vaccines, eliciting immune responses in vivo with IgG antibodies giving opsonic activity against five Australian GAS clinical isolates. However, to date, no investigation comparing the structure-activity relationship between the molecular weight of PEI and its adjuvanting activity in vaccine development has been performed. We hypothesized that the molecular weight and quantity of PEI in a liposomal vaccine will impact its adjuvanting properties. In this study, we successfully formulated liposomes containing different molecular weights of PEI (600, 1800, 10k and 25k Da) and equivalents of PEI (0.5, 1 and 2) of branched PEI. Outbred mice were administrated the vaccine formulations intranasally, and the mice that received a high ratio of PEI 600 reported a stronger immune response than the mice that received a lower ratio of PEI 600. Interestingly, mice that received the same quantity of PEI 600, PEI 10k and PEI 25k showed similar immune responses in vivo and in vitro. This comparative study highlights the ratio of PEI present in the liposome vaccines impacts adjuvanting activity, however, PEI molecular weight did not significantly enhance its adjuvanting properties. We also report that the stability of PEI liposomes is critical for vaccines to elicit the desired immune response.
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http://dx.doi.org/10.1016/j.bmcl.2021.127920DOI Listing
May 2021

A novel intracellular nanobody against HPV16 E6 oncoprotein.

Clin Immunol 2021 04 4;225:108684. Epub 2021 Feb 4.

The Laboratory of Developmental Genes and Human Diseases, Ministry of Education, Southeast University Medical School, 87 Dingjiaqiao Road, Nanjing 210009, China. Electronic address:

Cervical cancer occurs as a result of the persistent infection of high-risk human papillomavirus (HPV). HPV16 oncoproteins E6 and E7 exert different and concerted pro-tumor actions in cell transformation and malignance maintenance in various m echanisms. Nanobody expressed as "intracellular antibodies" (intrabodies) can target intracellular antigens to hamper their function efficaciously and specifically. In this work, phage-display approach was employed to select the high affinity HPV16 E6-specific nanobody, nanobody Nb9 against HPV16 E6 was selected. Nb9 has high affinity (Kaff =6.3 × 10 M) and can specifically bind endogenous HPV16 E6 protein in HPV16 positive CaSki and SiHa cells. In Nb9 overexpressed SiHa and CaSki cells, nucleus localization of HPV16 E6 was inhibited, p53 inactivation was prevented and increased apoptosis was observed. Moreover, tumor growth was inhibited in mouse xenograft model. Taken together, our results suggested that nanobody Nb9 could be a useful inhibitor for HPV16 E6 function and particularly appropriate for the treatment of HPV-associated disease.
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http://dx.doi.org/10.1016/j.clim.2021.108684DOI Listing
April 2021

Large-area, low-cost near-infrared meta-surface reflector based on a pixelated two-dimensional silicon disk array.

Opt Express 2020 Dec;28(25):38355-38365

All-dielectric meta-surfaces composed of dielectric meta-atoms with electric and magnetic multipole resonances provide a low loss alternative to plasmonic meta-surfaces in some optical research fields such as meta-lens and meta-surface holography. We utilize the digital holography lithography technique to obtain the large area meta-surface perfect reflector made of high refractive index and low loss silicon discs arrays, with the capability to delicately control the optical response in the near infrared spectrum. Three types of meta-surface reflectors (discs, truncated cones and diamond-shaped discs) were fabricated, which correspondingly exhibited nearly 1 peak reflectance and greater than 97% average reflectance in their respective perfect reflectance spectral regions. Digital holography lithography only takes 4 min to fabricate millions of photoresist disks over an area of 100 mm, which is high processing efficiency and low cost. The fabrication strategy opens a new avenue for the production of large-area meta-surfaces in the optical field, especially in the mass production of optical communication devices, semiconductor lasers, etc.
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http://dx.doi.org/10.1364/OE.412521DOI Listing
December 2020

Synthesis of Ni-Modified ZSM-5 Zeolites and Their Catalytic Performance in -Octane Hydroconversion.

Front Chem 2020 11;8:586445. Epub 2020 Dec 11.

State Key Laboratory of Heavy Oil Processing, China University of Petroleum, Beijing, China.

Ni-modified ZSM-5 zeolites with different nickel contents were successfully prepared by the synthesis method and the impregnation method. The synthesized samples were characterized by XRD, SEM, N adsorption-desorption isothermals, and Py-FTIR. The characterization results show that both the textural properties and crystallization of Ni-modified ZSM-5 zeolites were preserved well, and their acidic properties can be modulated after nickel modification. The corresponding NiMo catalysts supported on Ni-modified ZSM-5 zeolites were prepared by the incipient wetness co-impregnation method, and their catalytic performances were evaluated in -octane hydroconversion. Compared to the those modified by the synthesis method, ZSM-5 zeolite-supported catalysts modified by the impregnation method exhibit higher stability and higher isomerization selectivity. This is due to the synergistic effect between Brønsted acid sites and Lewis acid sites on the Ni-modified ZSM-5 zeolites, especially for the NiMo/1Ni-Z5 catalyst.
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http://dx.doi.org/10.3389/fchem.2020.586445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759625PMC
December 2020

A novel VEGFA mutation as a candidate for causing non-syndromic cleft lip and/or cleft palate.

Oral Dis 2020 Nov 15. Epub 2020 Nov 15.

Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, China.

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http://dx.doi.org/10.1111/odi.13719DOI Listing
November 2020

TCGA and ESTIMATE data mining to identify potential prognostic biomarkers in HCC patients.

Aging (Albany NY) 2020 11 11;12(21):21544-21558. Epub 2020 Nov 11.

Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.

Hepatocellular carcinoma (HCC) is an aggressive form of cancer characterized by a high recurrence rate following resection. Studies have implicated stromal and immune cells, which form part of the tumor microenvironment, as significant contributors to the poor prognoses of HCC patients. In the present study, we first downloaded gene expression datasets for HCC patients from The Cancer Genome Atlas database and categorized the patients into low and high stromal or immune score groups. By comparing those groups, we identified differentially expressed genes significantly associated with HCC prognosis. The Gene Ontology database was then used to perform functional enrichment analysis, and the STRING network database was used to construct protein-protein interaction networks. Our results show that most of the differentially expressed genes were involved in immune processes and responses and the plasma membrane. Those results were then validated using another a dataset from a HCC cohort in the Gene Expression Omnibus database and in 10 pairs of HCC tumor tissue and adjacent nontumor tissue. These findings enabled us to identify several tumor microenvironment-related genes that associate with HCC prognosis, and some those appear to have the potential to serve as HCC biomarkers.
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http://dx.doi.org/10.18632/aging.103943DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695391PMC
November 2020

Embedded flexible and transparent double-layer nickel-mesh for high shielding efficiency.

Opt Express 2020 Aug;28(18):26531-26542

An efficient approach to obtain high shielding effectiveness (SE) in transparent shielding in an optical window field is proposed and demonstrated by fabricating an embedded double-layer metallic mesh (DLMM) comprised of randomly structured Ni meshes on both sides of a flexible substrate, employing a facile and low-cost double-sided nanoimprinting method. The unique nonperiodic random structure contributes to uniform diffraction and eliminates the Moiré fringe generated by double-layer periodic meshes, ensuring high imaging quality for optical applications. The designed DLMM films simultaneously achieve strong shielding in the X-band and high transmittance in the visible spectrum, demonstrating a high transmittance of 88.7% at the 550-nm wavelength and a SE of 46.9 dB at a frequency of 8.2 GHz. An ultra-high SE of 80 dB is achieved at 64.2% transmittance, which reveals the highest reported SE over a metallic mesh for transparent shielding, indicating the high potential for this transparent electromagnetic interference shielding material for practical optical applications.
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http://dx.doi.org/10.1364/OE.401543DOI Listing
August 2020

A novel mutation revealed the cause of cleft lip and/or palate in a Chinese family.

Genes Dis 2020 Sep 18;7(3):440-447. Epub 2019 Dec 18.

Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, China.

Cleft lip and/or palate (CL/P) is a most common craniofacial birth defect which has multifactorial etiology. In our study, we aimed to discover the underlying etiological gene variation in a Chinese family diagnosed as non-syndromic CL/P (NSCL/P). The blood sample of the proband and her parents were detected by whole exome sequencing. The Mendelian inheritance pattern, allele frequency, variation location, function analysis and literature search were applied to filtrate and screen the mutation. Besides, the candidates were confirmed by Sanger sequencing. We meanwhile explored the conservative analysis and protein homology simulation. As a result, a start-lost mutation c.1A > GAtg/Gtg in the Frizzled-6 () gene predicting p.Met1 was detected. The variation has not been reported before and was predicted to be harmful. The alteration caused missing of two starting amino acids that are evolutionarily conserved for FZD6 protein. Moreover, the specific structure of the mutant protein obviously changed according to the results of the homologous model. In conclusion, the results suggest c.1A > GAtg/Gtg in the (NM_001164616) might be the genetic etiology for non-syndromic CL/P in this pedigree. Furthermore, this finding provided new etiologic information, supplementing the evidence that is a strong potential gene for CL/P.
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http://dx.doi.org/10.1016/j.gendis.2019.12.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7452514PMC
September 2020

Multi-AI competing and winning against humans in iterated Rock-Paper-Scissors game.

Sci Rep 2020 08 17;10(1):13873. Epub 2020 Aug 17.

National Engineering Research Center for Optical Instruments, Centre for Optical and Electromagnetic Research, Zhejiang University, Hangzhou, 310058, China.

Predicting and modeling human behavior and finding trends within human decision-making processes is a major problem of social science. Rock Paper Scissors (RPS) is the fundamental strategic question in many game theory problems and real-world competitions. Finding the right approach to beat a particular human opponent is challenging. Here we use an AI (artificial intelligence) algorithm based on Markov Models of one fixed memory length (abbreviated as "single AI") to compete against humans in an iterated RPS game. We model and predict human competition behavior by combining many Markov Models with different fixed memory lengths (abbreviated as "multi-AI"), and develop an architecture of multi-AI with changeable parameters to adapt to different competition strategies. We introduce a parameter called "focus length" (a positive number such as 5 or 10) to control the speed and sensitivity for our multi-AI to adapt to the opponent's strategy change. The focus length is the number of previous rounds that the multi-AI should look at when determining which Single-AI has the best performance and should choose to play for the next game. We experimented with 52 different people, each playing 300 rounds continuously against one specific multi-AI model, and demonstrated that our strategy could win against more than 95% of human opponents.
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http://dx.doi.org/10.1038/s41598-020-70544-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431549PMC
August 2020

Correction to: Pre-metastatic niche triggers SDF-1/CXCR4 axis and promotes organ colonisation by hepatocellular circulating tumour cells via downregulation of Prrx1.

J Exp Clin Cancer Res 2020 07 7;39(1):130. Epub 2020 Jul 7.

Second Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.

An amendment to this paper has been published and can be accessed via the original article.
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http://dx.doi.org/10.1186/s13046-020-01636-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7339500PMC
July 2020

p70S6K Promotes Acquired Resistance of Erlotinib Through Induction of Epithelial-Mesenchymal Transition in Non-Small Cell Lung Carcinoma.

Onco Targets Ther 2020 9;13:5257-5270. Epub 2020 Jun 9.

Department of Pharmacology, Nanjing Medical University, Nanjing, Jiangsu Province, People's Republic of China, 210029.

Background: Lung cancer is the leading cause of cancer-related deaths. EGFR tyrosine kinase inhibitors, such as erlotinib, were approved for non-small cell lung carcinoma patients with EGFR mutations. However, the acquired resistance of these inhibitors has not been fully clarified. Therefore, clarifying the mechanism and developing new rationales to overcome the drug resistance are urgently needed.

Methods: A pair of erlotinib sensitive and resistant cells was used to identify the key molecules in mediating erlotinib resistance. Loss- or gain-of-function study was used to confirm the effects of the key molecules. Xenograft mouse model and human cancer tissue sample studies were conducted for further corroboration.

Results: HCC827 cells with acquired resistance to erlotinib underwent epithelial-mesenchymal transition and exhibited enhanced p70S6K signaling compared to parental sensitive cells. Moreover, in erlotinib resistant cells, downregulation of p70S6K expression using either siRNA or shRNA reversed EMT and partially overcame erlotinib resistance. Meanwhile, in erlotinib sensitive cells, overexpression of p70S6K promoted EMT and induced erlotinib resistance. Upregulation of p70S6K signaling in erlotinib resistant cells was caused by reduced GSK3β-mediated protein degradation of mTOR and raptor. Additionally, p70S6K silencing suppressed the growth of erlotinib resistant cells in a xenograft mouse model. Finally, we found a correlation between p70S6K and E-cadherin expression in human non-small-cell lung cancer (NSCLC) tissue samples.

Conclusion: Our findings suggest that p70S6K-induced EMT plays an important role in the acquired resistance of erlotinib and provides a novel therapeutic rationale of targeting p70S6K in NSCLC therapy.
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http://dx.doi.org/10.2147/OTT.S249695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295111PMC
June 2020

Functional Characterization of a Novel IRF6 Frameshift Mutation From a Van Der Woude Syndrome Family.

Front Genet 2020 4;11:562. Epub 2020 Jun 4.

Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, China.

Background: Loss-of-function mutations in interferon regulatory factor-6 () are responsible for about 70% of cases of Van Der Woude Syndrome (VWS), an autosomal dominant developmental disorder characterized by pits and/or sinuses of the lower lip and cleft lip, cleft palate, or both.

Methods: We collected a Chinese Han VWS pedigree, performed sequencing and screening for the causal gene mutant. Initially, species conservation analysis and homology protein modeling were used to predict the potential pathogenicity of mutations. To test whether a VWS family-derived mutant variant of retained function, we carried out rescue assays in maternal-null mutant zebrafish embryos. To assess protein stability, we overexpressed reference and family-variants of IRF6 .

Results: We focused on a VWS family that includes a son with bilateral lip pits, uvula fissa and his father with bilateral cleft lip and palate. After sequencing and screening, a frameshift mutation of was identified as the potential causal variant (NM.006147.3, c.1088-1091delTCTA; p.Ile363ArgfsTer33). The residues in this position are strongly conserved among species and homology modeling suggests the variant alters the protein structure. In maternal-null mutant zebrafish embryos the periderm differentiates abnormally and the embryos rupture and die during gastrulation. Injection of mRNA encoding the reference variant of human IRF6, but not of the frame-shift variant, rescued such embryos through gastrulation. Upon overexpression in HEK293FT cells, the IRF6 frame-shift mutant was relatively unstable and was preferentially targeted to the proteasome in comparison to the reference variant.

Conclusion: In this VWS pedigree, a novel frameshift of was identified as the likely causative gene variant. It is a lost function mutation which could not rescue abnormal periderm phenotype in maternal-null zebrafish and which causes the protein be unstable through proteasome-dependent degradation.
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http://dx.doi.org/10.3389/fgene.2020.00562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289175PMC
June 2020

Kinesin family members KIF2C/4A/10/11/14/18B/20A/23 predict poor prognosis and promote cell proliferation in hepatocellular carcinoma.

Am J Transl Res 2020 15;12(5):1614-1639. Epub 2020 May 15.

Department of Oncology, Zhujiang Hospital, Southern Medical University 253 Industrial Avenue, Guangzhou 510282, China.

Kinesin superfamily proteins (KIFs) comprise a family of molecular motors that transport membranous organelles and protein complexes in a microtubule- and ATP-dependent manner, with multiple roles in cancers. Little is known about the function of KIFs in hepatocellular carcinoma (HCC). Here, we investigate the roles of KIFs in the prognosis and progression of HCC. Upregulation of eight KIFs (KIF2C, KIF4A, KIF10, KIF11, KIF14, KIF18B, KIF20A, and KIF23) was found to be significantly associated with the tumor stage and pathological tumor grade of HCC patients. Additionally, a high expression of these eight KIFs was significantly associated with shorter overall survival (OS) and disease-free survival (DFS) in patients with HCC. Cox regression analysis showed the mRNA expression levels of these eight KIF members to be independent prognostic factors for worse outcomes in HCC. Moreover, a risk score model based on the mRNA levels of the eight KIF members effectively predicted the OS rate of patients with HCC. Additional experiments revealed that downregulation of each of the eight KIFs effectively decreased the proliferation and increased the G1 arrest of liver cancer cells in vitro. Taken together, these results indicate that KIF2C/4A/10/11/14/18B/20A/23 may serve as prognostic biomarkers for survival and potential therapeutic targets in HCC patients.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7270015PMC
May 2020

The Adverse Impact of Glaucoma on Psychological Function and Daily Physical Activity.

J Ophthalmol 2020 21;2020:9606420. Epub 2020 Apr 21.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

Purpose: To evaluate the impact of glaucoma on vision-related quality of life and physical activity.

Methods: This study included 50 glaucoma patients and 50 healthy control subjects. Sociodemographic and clinical data were collected from all subjects. A Chinese version of the NEI VFQ-25 was used to evaluate the quality of life. Objective physical activity was assessed by wearing an accelerometer for 7 consecutive days.

Results: No significant difference was found in sociodemographic data between the two groups (all < 0.05). Visual acuity and visual field scores were worse in the glaucoma group than in the control group (all < 0.001). The VFQ-25 scores indicated significantly lower scores for ocular pain, social function, mental health, role difficulties, and color vision in the glaucoma group than in the normal group (all < 0.05). The average daily step count was lower in the glaucoma group than in the normal group. High, moderate, and low average daily step counts in the glaucoma group were associated with early-, moderate-, and advanced-stage glaucoma, respectively, while the step count was significantly lower in the advanced-stage glaucoma group than in the control group (=0.037). A positive relationship was found between the average daily step count and social function and mental health (both < 0.05).

Conclusions: We demonstrated an adverse impact of glaucoma on psychological function and daily physical activity. Social function and mental health showed declines in glaucoma patients, and physical activity was limited in patients with advanced-stage glaucoma.
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http://dx.doi.org/10.1155/2020/9606420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191398PMC
April 2020

Prognostic Values of Transforming Growth Factor-Beta Subtypes in Ovarian Cancer.

Biomed Res Int 2020 12;2020:2170606. Epub 2020 Apr 12.

Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.

Purpose: To explore the potential role of the transforming growth factor-beta (TGF-) subtypes in the prognosis of ovarian cancer patients. . The prognostic roles of individual TGF- subtypes in women with ovarian cancer were retrieved from the Kaplan-Meier plotter (KM plotter) database. In addition, the Oncomine database and immunohistochemistry were used to observe the mRNA and protein expression of TGF- subtypes between human ovarian carcinoma and normal ovarian samples, respectively.

Results: TGF-1 and TGF-4 were totally uncorrelated with survival outcomes in women with ovarian cancer. Increased TGF-2 and TGF-3 mRNA expression was markedly related to unfavorable prognosis, especially in women with serous, poorly differentiated, and late-stage ovarian carcinoma. High expression levels of TGF-2 were related to worse progression-free survival (PFS) while TGF-3 was linked to unfavorable overall survival (OS) and PFS in women with TP53-mutated ovarian cancer. TGF-2 was associated with poor OS and PFS from treatment with chemotherapy with platins, Taxol, or a platin+Taxol. However, overexpression of TGF-3 was associated with poor OS from the use of platins and poor PFS of Taxol or a platin+Taxol in women with ovarian carcinoma. Furthermore, the expression of TGF-2 mRNA and protein was higher but only TGF-3 mRNA expression was higher in cancerous tissues than in normal ovarian samples.

Conclusion: Higher expression of TGF-2 functioned as a significant predictor of poor prognosis in women with ovarian cancer, especially those with TP53 mutations or who were undergoing chemotherapy with platins, Taxol, or a platin+Taxol.
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http://dx.doi.org/10.1155/2020/2170606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7174935PMC
February 2021

Photoflexoelectric effect in halide perovskites.

Nat Mater 2020 Jun 20;19(6):605-609. Epub 2020 Apr 20.

Institucio Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Catalonia.

Harvesting environmental energy to generate electricity is a key scientific and technological endeavour of our time. Photovoltaic conversion and electromechanical transduction are two common energy-harvesting mechanisms based on, respectively, semiconducting junctions and piezoelectric insulators. However, the different material families on which these transduction phenomena are based complicate their integration into single devices. Here we demonstrate that halide perovskites, a family of highly efficient photovoltaic materials, display a photoflexoelectric effect whereby, under a combination of illumination and oscillation driven by a piezoelectric actuator, they generate orders of magnitude higher flexoelectricity than in the dark. We also show that photoflexoelectricity is not exclusive to halides but a general property of semiconductors that potentially enables simultaneous electromechanical and photovoltaic transduction and harvesting in unison from multiple energy inputs.
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http://dx.doi.org/10.1038/s41563-020-0659-yDOI Listing
June 2020

A Five-Genes-Based Prognostic Signature for Cervical Cancer Overall Survival Prediction.

Int J Genomics 2020 25;2020:8347639. Epub 2020 Mar 25.

Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, China.

. This study is aimed at identifying a prognostic signature for cervical cancer. . The gene expression data and clinical information of cervical cancer and normal cervical tissues were acquired from The Cancer Genome Atlas and from three datasets of the Gene Expression Omnibus database. DESeq2 and Limma were employed to screen differentially expressed genes (DEGs). The overlapping DEGs among all datasets were considered the final DEGs. Then, the functional enrichment analysis was performed. Moreover, the Cox proportional hazards regression was performed to establish a prognostic signature of the DEGs. The Kaplan-Meier analysis was applied to test the model. Relationships between gene expression and clinicopathological parameters in cervical cancer, including age, HPV status, histology, stage, and lymph node metastasis, were analysed by the chi-square test. The somatic mutations of these prognostic genes were assessed through cBioPortal. The robustness of the model was verified in another two independent validation cohorts. . In total, 169 overlapping upregulated genes and 29 overlapping downregulated genes were identified in cervical cancer compared with normal cervical tissues. Functional enrichment analysis indicated that the DEGs were mainly enriched in DNA replication, the cell cycle, and the p53 signalling pathway. Finally, a 5-gene- (ITM2A, DSG2, SPP1, EFNA1, and MMP1) based prognostic signature was built. According to this model, each patient was given a prognostic-related risk value. The Kaplan-Meier analysis showed that a higher risk was related to worse overall survival in cervical cancer, with an area under the receiver operating characteristic curve of 0.811 for 15 years. The validity of this model in the prediction of cervical cancer outcome was verified in another two independent datasets. In addition, our study also found that the low expression of ITM2A was associated with cervical adenocarcinoma. Interestingly, DSG2 was associated with the HPV status of cervical cancer. . Our study constructed a prognostic model in cervical cancer and discovered two novel genes, ITM2A and DSG2, associated with cervical carcinogenesis and survival.
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http://dx.doi.org/10.1155/2020/8347639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136791PMC
March 2020

Glasgow Coma Scale is a better delayed neurological sequelae risk factor than neurological examination abnormalities in carbon monoxide poisoning.

Am J Emerg Med 2020 11 24;38(11):2468-2469. Epub 2020 Feb 24.

Clinical Laboratory Department, Fushun People's Hospital, 490 Jixiang road, Fushun, Zigong, Sichuan, China. Electronic address:

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http://dx.doi.org/10.1016/j.ajem.2020.02.047DOI Listing
November 2020

A mechanically bendable and conformally attachable polymer membrane microlaser array enabled by digital interference lithography.

Nanoscale 2020 Mar 12;12(12):6736-6743. Epub 2020 Mar 12.

School of Optoelectronic Science and Engineering & Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou 215006, China.

The progressive miniaturization and thinning of photonic devices would enable the realization of multi-functional photonic integrated circuits and expand the application frontier to novel fields including wearable and disposable electronics. Herein, we have demonstrated a mechanically bendable and conformally attachable polymer membrane microcavity laser array using digital interference lithography. The developed lithography system could distribute a number of subwavelength grating pixels with both high efficiency (1k pixels per second) and excellent versatility (ease of control in the pixel size, spacing, and grating periodicity) as the microcavity laser array, in which a pair of subwavelength gratings constitutes a distributed Bragg resonator microcavity via coherent interference, furnishes a vertically emitting microcavity laser array for convenient light coupling and utilization. The microlaser array polymer membrane presented a total thickness of only 30 μm with excellent performance stability and reliability against long time operation and harsh environmental conditions, which could be further reversibly stretched, repeatedly bendable and conformally attached onto rounded or irregular surfaces or biological tissues with no degradation in single-mode or low-threshold characteristics, paving a way for on-chip optical functionalization toward wearable electronics and outdoor environmental monitoring applications.
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http://dx.doi.org/10.1039/c9nr10970fDOI Listing
March 2020

Identification of rare nonsense variant causing orofacial cleft in a Chinese family and an up-to-date genotype-phenotype analysis.

Genes Dis 2021 Sep 8;8(5):689-697. Epub 2020 Jan 8.

Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, 100081, PR China.

The Patched 1 () gene encodes a membrane receptor involved in the Hedgehog (Hh) signaling pathway, an abnormal state of which may result in congenital defects or human tumors. In this study, we conducted whole-exome sequencing on a three-generation Chinese family characterized with variable penetrance of orofacial clefts. A rare heterozygous variant in the gene (c.2833C > T p.R945X) was identified as a disease-associated mutation. Structural modeling revealed a truncation starting from the middle of the second extracellular domain of PTCH1 protein. This may damage its ligand recognition and sterol transportation abilities, thereby affecting the Hh signaling pathway. Biochemical assays indicated that the R945X protein had reduced stability compared to the wild-type . In addition, we reviewed the locations and mutation types of variants in individuals with clefting phenotypes, and analyzed the associations between clefts and locations or types of variants within . Our findings provide further evidence that variants result in orofacial clefts, and contributed to genetic counseling and clinical surveillance in this family.
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http://dx.doi.org/10.1016/j.gendis.2019.12.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278535PMC
September 2021

Pre-metastatic niche triggers SDF-1/CXCR4 axis and promotes organ colonisation by hepatocellular circulating tumour cells via downregulation of Prrx1.

J Exp Clin Cancer Res 2019 11 21;38(1):473. Epub 2019 Nov 21.

Second Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.

Background: Circulating tumour cells (CTCs), especially mesenchymal CTCs, are important determinants of metastasis, which leads to most recurrence and mortality in hepatocellular carcinoma (HCC). However, little is known about the underlying mechanisms of CTC colonisation in pre-metastatic niches.

Methods: Detection and classification of CTCs in patients were performed using the CanPatrol™ system. A lentiviral vector expressing Prrx1-targeting shRNA was constructed to generate a stable HCC cell line with low expression of Prrx1. The effect of Prrx1 knockdown on stemness, migration, and drug resistance of the cell line was assessed, including involvement of SDF-1/CXCR4 signalling. Promising clinical applications of an inhibitor of STAT3 tyrosine phosphorylation, C188-9, and specific blockade with CXCR4 antibody were explored.

Results: The number of mesenchymal CTCs in blood was closely associated with tumour recurrence or metastasis. Pre-metastatic niche-derived SDF-1 could downregulate Prrx1, which induced the stemness, drug resistance, and increased expression of CXCR4 in HCC cells through the STAT3 pathway in vitro. In vivo, mice bearing tumours of Prrx1 low-expressing cells had significantly shorter survival. In xenograft tumours and clinical samples, loss of Prrx1 was negatively correlated with increased expression of CXCR4 in lung metastatic sites compared with that in the primary foci.

Conclusions: These findings demonstrate that decreased expression of Prrx1 stimulates SDF-1/CXCR4 signalling and contributes to organ colonisation with blood CTCs in HCC. STAT3 inhibition and specific blockade of CXCR4 have clinical potential as therapeutics for eliminating organ metastasis in advanced HCC.
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http://dx.doi.org/10.1186/s13046-019-1475-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6873584PMC
November 2019

Highly flexible electrochromic devices enabled by electroplated nickel grid electrodes and multifunctional hydrogels.

Opt Express 2019 Oct;27(21):29547-29557

Flexible electronics, as a futuristic technology, is presenting tremendous impact in areas of wearable displaying, energy saving, and adaptive camouflage. In this work, we constructed a simple triple-layered electrochemical device with high flexibility using the electroplated nickel (Ni) grid electrode and the multifunctional hydrogel. The Ni grid electrode with low resistance (0.5 Ω/sq), high optical transparency (84.8%) and good mechanical flexibility, is beneficial for efficient electron injection, while the transparent lithium chloride hydrogel functions simultaneously for ion storage, ion transportation and counter-conducting. The thin polymer poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate) (PEDOT: PSS) film is utilized as the electrochromic (EC) material and it also distributes the electrons evenly for uniform coloration. The triple-layered EC architecture not only simplifies the manufacturing procedures but also improves the device performance in terms of optical contrast and mechanical robustness. The device shows fast response for coloration and bleaching with an absolute transmittance contrast of 40% and a contrast retention over 72% after 2500 bending cycles. The ability of the flexible electrochromic device for conformable attaching was also investigated without obvious performance degradation. The electroplated Ni grid electrode and the multifunctional hydrogel are advantageous in constructing flexible electrochromic devices in terms of the response time, the working stability and the bending capability, paving a way for next-generation flexible electronics.
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http://dx.doi.org/10.1364/OE.27.029547DOI Listing
October 2019

Stimulated transformation of soft helix among helicoidal, heliconical, and their inverse helices.

Sci Adv 2019 10 4;5(10):eaax9501. Epub 2019 Oct 4.

Advanced Materials and Liquid Crystal Institute and Chemical Physics Interdisciplinary Program, Kent State University, Kent, OH 44242, USA.

Dynamic modulation of soft helix in terms of the molecular organization, handedness, and pitch length could result in a sophisticated control over its functions, opening numerous possibilities toward the exploration of previously unidentified applications. Here, we report a dynamic and reversible transformation of a soft helical superstructure among the helicoidal (molecules orthogonal to helical axis), heliconical (molecules oblique to the helical axis, i.e., oblique helicoidal), and their inverse helices, together with a tunability on the helical pitch, by combining electrical and optical manipulations. This multistate transformation depends on a matching of the temperature, the strength of external stimuli, and the bend and twist elastic effects of the system. A laser emission with tunable wavelength and polarization, and prescribed micropatterns formed by any aforementioned architectures were achieved.
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http://dx.doi.org/10.1126/sciadv.aax9501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6777971PMC
October 2019

Multiple Anti-Counterfeiting Guarantees from a Simple Tetraphenylethylene Derivative - High-Contrasted and Multi-State Mechanochromism and Photochromism.

Angew Chem Int Ed Engl 2019 Dec 22;58(49):17814-17819. Epub 2019 Oct 22.

Department of Chemistry, Hong Kong Branch of Chinese National Engineering Research, Center for Tissue Restoration and Reconstruction, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.

Herein the novel tetraphenylethylene (TPE) derivative 1 was designed with an integration of aggregation-induced emission (AIE), multi-state mechanochromism and self-recovery photochromism. The molecule was susceptible to grinding, heating and vapor fuming and showed corresponding transition of its emission colors. The heated powder or single crystal of 1 exhibited reversible photochromism. After a short period of UV irradiation, it showed a bright red color, but recovered to its original white appearance within 1 min. The photochromism is due to the formation of photocyclization intermediates upon UV irradiation, while the eversible mechanochromism is attributed to the weak molecular interactions derived from head-to-tail stacking of the molecules. This reversible multi-state, high-contrasted and rapid responsive mechanochromic and photochromic property cooperatively provide double enhancement of a multimode guarantee in advanced anti-counterfeiting.
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http://dx.doi.org/10.1002/anie.201910530DOI Listing
December 2019
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