Publications by authors named "Dan Guo"

324 Publications

Biosynthesis of UDP-2-acetamido-4-formamido-2,4,6-trideoxy-hexose by WekG, WekE, WekF, and WekD: Enzymes in the Wek pathway responsible for O-antigen Assembly in Escherichia coli O119.

Carbohydr Res 2021 Jul 7;507:108388. Epub 2021 Jul 7.

TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin, China; Key Laboratory of Microbial Functional Genomics, Tianjin, China; The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Nankai University, Tianjin, China. Electronic address:

Considering the importance of bacterial glycoconjugates on virulence and host mimicry, there is a need to better understand the biosynthetic pathways of these unusual sugars to identify critical targets involved in bacterial pathogenesis. In this report, we describe the cloning, overexpression, purification, and biochemical characterization of the four central enzymes in the biosynthesis pathway for UDP-2-acetamido-4-formamido-2,4,6-trideoxy-hexose, WekG, WekE, WekF, and WekD. Product peaks from enzyme-substrate reactions were detected by using a combination of capillary electrophoresis (CE) and electrospray ionization-mass spectrometry (ESI-MS). Putative enzyme assignments were provided by protein sequence analysis. Combined with the mass spectrometric characterization of pathway intermediates, we propose a biosynthetic pathway for UDP-2-acetamido-4-formamido-2,4,6-trideoxy-hexose. This process involves C-4, C-6 dehydration, C-4 amination, and formylation. CID-ESI-MS result confirmed that the final product is a 4 formamido derivative too rather than the 3 formamido derivatives as reported earlier.
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http://dx.doi.org/10.1016/j.carres.2021.108388DOI Listing
July 2021

Mortality prediction for patients with acute respiratory distress syndrome based on machine learning: a population-based study.

Ann Transl Med 2021 May;9(9):794

Department of Intensive Care Unit, Shenzhen Hospital, Southern Medical University, Shenzhen, China.

Background: Traditional scoring systems for patients' outcome prediction in intensive care units such as Oxygenation Saturation Index (OSI) and Oxygenation Index (OI) may not reliably predict the clinical prognosis of patients with acute respiratory distress syndrome (ARDS). Thus, none of them have been widely accepted for mortality prediction in ARDS. This study aimed to develop and validate a mortality prediction method for patients with ARDS based on machine learning using the Medical Information Mart for Intensive Care (MIMIC-III) and Telehealth Intensive Care Unit (eICU) Collaborative Research Database (eICU-CRD) databases.

Methods: Patients with ARDS were selected based on the Berlin definition in MIMIC-III and eICU-CRD databases. The APPS score (using age, PaO/FiO, and plateau pressure), Simplified Acute Physiology Score II (SAPS-II), Sepsis-related Organ Failure Assessment (SOFA), OSI, and OI were calculated. With MIMIC-III data, a mortality prediction model was built based on the random forest (RF) algorithm, and the performance was compared to those of existing scoring systems based on logistic regression. The performance of the proposed RF method was also validated with the combined MIMIC-III and eICU-CRD data. The performance of mortality prediction was evaluated by using the area under the receiver operating characteristics curve (AUROC) and performing calibration using the Hosmer-Lemeshow test.

Results: With the MIMIC-III dataset (308 patients, for comparisons with the existing scoring systems), the RF model predicted the in-hospital mortality, 30-day mortality, and 1-year mortality with an AUROC of 0.891, 0.883, and 0.892, respectively, which were significantly higher than those of the SAPS-II, APPS, OSI, and OI (all P<0.001). In the multi-source validation (the combined dataset of 2,235 patients in MIMIC-III and 331 patients in eICU-CRD), the RF model achieved an AUROC of 0.905 and 0.736 for predicting in-hospital mortality for the MIMIC-III and eICU-CRD datasets, respectively. The calibration plots suggested good fits for our RF model and these scoring systems for predicting mortality. The platelet count and lactate level were the strongest predictive variables for predicting in-hospital mortality.

Conclusions: Compared to the existing scoring systems, machine learning significantly improved performance for predicting ARDS mortality. Validation with multi-source datasets showed a relatively robust generalisation ability of our prediction model.
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http://dx.doi.org/10.21037/atm-20-6624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246239PMC
May 2021

MIER3 induces epithelial-mesenchymal transition and promotes breast cancer cell aggressiveness via forming a co-repressor complex with HDAC1/HDAC2/Snail.

Exp Cell Res 2021 Jul 6;406(1):112722. Epub 2021 Jul 6.

Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China; Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China. Electronic address:

Breast cancer is one of the most frequently diagnosed cancers and the leading cause of cancer death in women. MIER3 (Mesoderm induction early response 1, family member3) is considered as a potential oncogene for breast cancer. However, the role of MIER3 in breast cancer remain largely unknown. The expression of MIER3 was detected and the relationship between its expression and clinicopathological characteristics was also analyzed. The effect of MIER3 on proliferation and migration of breast cancer cells was detected in vitro and in vivo. Western blot, IF, and Co-IP were employed to detect the relationship between MIER3, HDAC1, HDAC2, and Snail. ChIP assay was performed to determine the binding of MIER3/HDAC1/HDAC2/Snail complex to the promoter of E-cadherin. In this study, we found that MIER3 was upregulated in breast cancer tissue and closely associated with poor prognosis of patients. MIER3 could promote the proliferation, migration, and epithelial-mesenchymal transition (EMT) of breast cancer cells. Further studies showed that MIER3 interacted with HDAC1/HDAC2 and Snail to form a repressive complex which could bind to E-cadherin promoter and was related to its deacetylation. Our study concluded that MIER3 was involved in forming a co-repressor complex with HDAC1/HDAC2/Snail to promote EMT by silencing E-cadherin.
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http://dx.doi.org/10.1016/j.yexcr.2021.112722DOI Listing
July 2021

Molecular chaperone Hsp90 protects KCBP from degradation by proteasome in Dunaliella salina cells.

Folia Microbiol (Praha) 2021 Jul 8. Epub 2021 Jul 8.

Laboratory for Cell Biology, the First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, China.

Kinesin-like calmodulin-binding protein (KCBP) is a unique kinesin with half kinesin and half myosin, with kinesin motor domain at C-terminus and myosin tail homology region 4 (MyTH4) and band 4.1, ezrin, radixin, moesin (FERM) domains at N-terminus. The special structure endows KCBP multi-intracellular functions, including cell division, trichome morphogenesis in plants, and flagellar function in algae. However, little is known about the molecular mechanism underlying these functions. Here, we identified a molecular chaperone Hsp90 as a novel binding partner with KCBP in Dunaliella salina using a yeast two-hybrid screen. Further analysis showed that Hsp90 interacted with both the N-terminal and C-terminal of DsKCBP. Since Hsp90 was involved in the stability and proteolytic turnover of numerous proteins, whether Hsp90 regulated the degradation of DsKCBP was investigated. Our results showed that both Hsp90 and DsKCBP presented in the purified proteasome, and the interaction of DsKCBP-Hsp90 was inhibited upon Hsp90 inhibitor geldanamycin treatment. The level of DsKCBP proteins was diminished remarkably indicating that the disassociation of DsKCBP from Hsp90 accelerated the degradation of the former. Furthermore, immunofluorescence results showed that the localization of DsKCBP at basal body and flagella was disappeared by Hsp90 inhibition. The increased mRNA level of DsKCBP during flagellar assembly was not obvious by geldanamycin treatment. These data provided evidence that Hsp90 protected DsKCBP from degradation by proteasome and was involved in the role of DsKCBP in flagellar assembly.
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http://dx.doi.org/10.1007/s12223-021-00897-7DOI Listing
July 2021

Full-color WGM lasing in nested microcavities.

Nanoscale 2021 Jun;13(24):10792-10797

College of Physics and Optoelectronics, Faculty of Science, Beijing University of Technology, Beijing 100124, China.

A full-color whispering-gallery mode (WGM) laser has been fabricated by partitioning different light-emitting polymers in a nested microcavity. Red-green-blue WGM lasing with a high quality factor above 104 and a narrow linewidth of 0.025 nm emits from nested capillaries when excited with a nanosecond laser. The full-color WGM lasing shows a low excitation threshold for the nested microcavities, which can avoid fluorescence resonant energy transfer. We also achieve wavelength tunable lasing upon altering the different polymers in the nested microcavities. The work demonstrates a simple method to fabricate a full-color WGM laser and its potential applications in compact lighting devices and white laser sources.
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http://dx.doi.org/10.1039/d1nr01052bDOI Listing
June 2021

Context-Aware Graph Inference with Knowledge Distillation for Visual Dialog.

IEEE Trans Pattern Anal Mach Intell 2021 Jun 1;PP. Epub 2021 Jun 1.

Visual dialog is a challenging task that requires the comprehension of the semantic dependencies among implicit visual and textual contexts. This task can refer to the relational inference in a graphical model with sparse contextual subjects (nodes) and unknown graph structure (relation descriptor); how to model the underlying context-aware relational inference is critical. To this end, we propose a novel Context-Aware Graph (CAG) neural network. We focus on the exploitation of fine-grained relational reasoning with object-level visual-historical co-reference nodes. The graph structure (relation in dialog) is iteratively updated using an adaptive top-K message passing mechanism. To eliminate sparse useless relations, each node has dynamic relations in the graph (different related K neighbor nodes), and only the most relevant nodes are attributive to the context-aware relational graph inference. In addition, to avoid negative performance caused by linguistic bias of history, we propose a pure visual-aware knowledge distillation mechanism named CAG-Distill, in which image-only visual clues are used to regularize the joint visual-historical contextual awareness. Experimental results on VisDial v0.9 and v1.0 datasets show that both CAG and CAG-Distill outperform comparative methods. Visualization results further validate the remarkable interpretability of our graph inference solution.
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http://dx.doi.org/10.1109/TPAMI.2021.3085755DOI Listing
June 2021

In vitro and in vivo anti-metastatic effect of the alkaliod matrine from Sophora flavecens on hepatocellular carcinoma and its mechanisms.

Phytomedicine 2021 Jul 27;87:153580. Epub 2021 Apr 27.

Department of Pharmacy, Nanfang Hospital, Southern Medical University, No. 1838, Guangzhou Boulevard (North), Guangzhou 510515, China; Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China. Electronic address:

Backgrounds: Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal cancer with high metastasis and recurrence rates. Hypoxia-induced miRNAs and HIF-1α are demonstrated to play essential roles in tumor metastasis. Matrine (CHNO), an alkaloid extracted from Sophora flavescens Aiton, has been used as adjuvant therapy for liver cancer in China. The anti-metastasis effects of matrine on HCC and the underlying mechanisms remain poorly understood.

Purpose: We aimed to investigate the effects of matrine on metastasis of HCC both in vitro and in vivo, and explored whether miR-199a-5p and HIF-1α are involved in the action of matrine.

Methods: MTT method, colony formation, wound healing and matrigel transwell assays were performed to evaluate the effects of matrine on cell proliferation, migration and invasion. Nude mice xenograft model and immunohistochemistry (IHC) assay were employed to investigate the anti-metastatic action of matrine in vivo. Quantitative real-time PCR, western blot and dual luciferase reporter assay were conducted to determine the underlying mechanisms of matrine.

Results: Matrine exerted stronger anti-proliferative action on Bel7402 and SMMC-7721 cells under hypoxia than that in normoxia. Both matrine and miR-199a-5p exhibited significant inhibitory effects on migration, invasion and EMT in Bel7402 and SMMC-7721 cells under hypoxia. Further study showed that miR-199a-5p was downregulated in HCC cell lines, and this microRNA was identified to directly target HIF-1α, resulting in decreased HIF-1α expression. Matrine induced miR-199a-5p expression, decreased HIF-1α expression and inhibited metastasis of Bel7402 and SMMC-7721 cells, while miR-199a-5p knockdown reversed the inhibitory effects of matrine on cell migration, invasion, EMT and HIF-1α expression. In vivo, matrine showed significant anti-metastatic activity in the nude mouse xenograft model. H&E and IHC analysis indicated that lung and liver metastasis nodules were reduced, and the protein expression of HIF-1α and Vimentin were significantly decreased by i.p injection of matrine.

Conclusions: Matrine exhibits significant anti-metastatic effect on HCC, which is attributed to enhanced miR-199a-5p expression and subsequently impaired HIF-1α signaling and EMT. These findings suggest that miR-199a-5p is a potential therapeutic target of HCC, and matrine may represent a promising anti-metastatic medication for HCC therapy.
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http://dx.doi.org/10.1016/j.phymed.2021.153580DOI Listing
July 2021

Adiposity Measurements and Metabolic Syndrome Are Linked Through Circulating Neuregulin 4 and Adipsin Levels in Obese Adults.

Front Physiol 2021 4;12:667330. Epub 2021 May 4.

Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Background: Adiposity and adipokines are associated with metabolic disorders, but little is known regarding that whether adiposity measurements link metabolic syndrome (MetS) through circulating neuregulin 4 (Nrg4) and adipsin levels.

Materials And Methods: A total of 1212 subjects with a waist circumference greater than 90 cm for men or 80 cm for women were enrolled from a Chinese community. Circulating Nrg4 and adipsin levels were measured using commercial kits. Mediation analyses of circulating Nrg4 and adipsin were performed in the study using linear and logistic regression.

Results: Subjects with MetS had higher waist circumference, visceral fat level, and circulating adipsin level, and lower levels of circulating Nrg4 and muscle mass to visceral fat (MVF) ratio (all < 0.05). In multivariable logistic regression analyses, after adjusting for confounding variables, per standard deviation (SD) increase in waist circumference and visceral fat level were significantly associated with increased odds of MetS [OR (95% CI), 1.42 (1.22-1.64); 2.20 (1.62-2.99); respectively]; and per SD reduction in MVF ratio was significantly associated with reduced odds of MetS [OR (95% CI), 0.65 (0.55-0.77)]. In the mediation analyses, both circulating Nrg4 and adipsin levels mediated the association between waist circumference (8.31% and 18.35%, respectively), visceral fat level (7.50% and 9.98%, respectively), and MVF ratio (5.80% and 9.86%, respectively) and MetS after adjustments.

Conclusion: These findings indicate that adiposity measurements and MetS are linked through circulating Nrg4 and adipsin levels in obese adults, suggesting that circulating Nrg4 and adipsin levels might be potential predictors for management of MetS.
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http://dx.doi.org/10.3389/fphys.2021.667330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129583PMC
May 2021

Developmental validation of the Microreader™ Y Prime Plus ID System: An advanced Y-STR 38-plex system for forensic applications.

Sci Justice 2021 May 30;61(3):260-270. Epub 2021 Jan 30.

Forensic Science Service of the Beijing Public Security Bureau, 100192 Beijing, China. Electronic address:

Y-STR is widely used in sexual assaults and familial searches of suspects. Here, we reported a novel 38-plex STR genotyping system designed for forensic applications. Microreader™ Y Prime Plus ID System (YPP) amplifies 38 loci in one reaction, including 29 loci from commonly used Yfiler® Plus PCR Amplification Kit & PowerPlex® Y23 System (DYS393, DYS570, DYS19, DYS392, DYS549, Y GATA H4, DYS460, DYS458, DYS481, DYS635, DYS448, DYS533, DYS449, DYS456, DYS389I, DYS390, DYS389Ⅱ, DYS438, DYS391, DYS439, DYS437, DYS385a/b, DYS643, DYS518, DYS576, DYF387S1a/b, and DYS627), 6 commonly used loci for the Y-STR database (DYS444, DYS447, DYS596, DYF404a/b, DYS527a/b, DYS557) and one Y-indel specific for the Chinese population. YPP is designed for different types of samples, such as blood card and swabs. In this work, YPP was validated following SWGDAM guidelines (2016) and guidelines from Ministry of Public Security of the People's Republic of China, including PCR-based, sensitivity, accuracy and precision, mixture, stability and inhibitor, and species specificity. The results indicate that the Microreader™ Y Prime Plus ID System is a powerful identification kit designed for forensic databases.
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http://dx.doi.org/10.1016/j.scijus.2021.01.003DOI Listing
May 2021

GADD45g acts as a novel tumor suppressor and its activation confers new combination regimens for the treatment of AML.

Blood 2021 May 4. Epub 2021 May 4.

Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.

Acute myeloid leukemia (AML) is an aggressive hematopoietic malignancy for which there is an unmet need for novel treatment strategies. Here, we characterize the growth arrest and DNA damage-inducible gene gamma (GADD45g) as a novel tumor suppressor in AML. We show that GADD45g is preferentially silenced in AML, especially in AML with FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutations and mixed-lineage leukemia (MLL)-rearrangements, and reduced expression of GADD45g is correlated with poor prognosis in AML patients. Upregulation of GADD45g impairs homologous recombination (HR) DNA repair, leading to DNA damage accumulation, and dramatically induces apoptosis, differentiation, growth arrest and increases sensitivity of AML cells to chemotherapeutic drugs, without affecting normal cells. In addition, GADD45g is epigenetically silenced by histone deacetylation in AML, and its expression is further downregulated by oncogenes FLT3-ITD and MLL-AF9 in patients carrying these genetic abnormalities. Combination of histone deacetylase 1/2 inhibitor Romidepsin with FLT3 tyrosine kinase inhibitor AC220 or bromodomain inhibitor JQ1 exert synergistic anti-leukemic effects on FLT3-ITD+ and MLL-AF9+ AML, respectively, by dually activating GADD45g. These findings uncover hitherto unreported evidence for the selective anti-leukemia role of GADD45g and provide novel strategies for the treatment of FLT3-ITD+ and MLL-AF9+ AML.
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http://dx.doi.org/10.1182/blood.2020008229DOI Listing
May 2021

Study of a Gate-Engineered Vertical TFET with GaSb/GaAsSb Heterojunction.

Materials (Basel) 2021 Mar 15;14(6). Epub 2021 Mar 15.

Key Laboratory for Wide-Band Gap Semiconductor Materials and Devices of Education, The School of Microelectronics, Xidian University, Xi'an 710071, China.

It is well known that the vertical tunnel field effect transistor (TFET) is easier to fabricate than the conventional lateral TFETs in technology. Meanwhile, a lightly doped pocket under the source region can improve the subthreshold performance of the vertical TFETs. This paper demonstrates a dual material gate heterogeneous dielectric vertical TFET (DMG-HD-VTFET) with a lightly doped source-pocket. The proposed structure adopts a GaSb/GaAsSb heterojunction at the source and pocket to improve the band-to-band tunneling (BTBT) rate; at the same time, the gate electrode is divided into two parts, namely a tunnel gate (M1) and control gate (M2) with work functions Φ and Φ, where Φ > Φ. In addition, further performance enhancement in the proposed device is realized by a heterogeneous dielectric corresponding to a dual material gate. Simulation results indicate that DMG-HD-VTFET and HD-VTFET possess superior metrics in terms of DC (Direct Current) and RF (Radio Frequency) performance as compared with conventional VTFET. As a result, the ON-state current of 2.92 × 10 A/μm, transconductance of 6.46 × 10 S/μm, and average subthreshold swing (SS) of 18.1 mV/Dec at low drain voltage can be obtained. At the same time, DMG-HD-VTFET could achieve a maximum f of 459 GHz at 0.72 V gate-to-source voltage (V) and a maximum gain bandwidth (GBW) of 35 GHz at V = 0.6 V, respectively. So, the proposed structure will have a great potential to boost the device performance of traditional vertical TFETs.
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http://dx.doi.org/10.3390/ma14061426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998445PMC
March 2021

A circular RNA derived from PLXNB2 as a valuable predictor of the prognosis of patients with acute myeloid leukaemia.

J Transl Med 2021 03 23;19(1):123. Epub 2021 Mar 23.

Department of Hematology, The First Affiliated Hospital, Harbin Medical University, 23 Youzheng Street, Nan Gang District, Harbin, 150001, China.

Background: As a common haematological malignancy, acute myeloid leukaemia (AML), particularly with extramedullary infiltration (EMI), often results in a high mortality rate and poor prognosis. Circular RNAs (circRNAs) regulate biological and pathogenic processes, suggesting a potential role in AML. We have previously described the overall alterations in circRNAs and their regulatory networks between patients with AML presenting with and without EMI. This study aims to find new prognostic and therapeutic targets potentially associated with AML.

Methods: qRT-PCR was performed on samples from 40 patients with AML and 15 healthy controls. The possibility of using circPLXNB2 (circRNA derived from PLXNB2) as a diagnostic and prognostic biomarker for AML was analysed with multiple statistical methods. In vitro, the function of circPLXNB2 was studied by lentivirus transfection, CCK-8 assays, flow cytometry, and Transwell experiments. Western blotting and qRT-PCR were performed to detect the expression of related proteins and genes. The distribution of circPLXNB2 in cells was observed using RNA fluorescence in situ hybridization (RNA-FISH). We also investigated the role of circPLXNB2 by establishing AML xenograft models in NOD/SCID mice.

Results: By analysing the results of qRT-PCR detection of clinical samples, the expression of the circPLXNB2 and PLXNB2 mRNAs were significantly increased in patients with AML, more specifically in patients with AML presenting with EMI. High circPLXNB2 expression was associated with an obviously shorter overall survival and leukaemia-free survival of patients with AML. The circPLXNB2 expression was positively correlated with PLXNB2 mRNA expression, as evidenced by Pearson's correlation analysis. RNA-FISH revealed that circPLXNB2 is mainly located in the nucleus. In vitro and in vivo, circPLXNB2 promoted cell proliferation and migration and inhibited apoptosis. Notably, circPLXNB2 also increased the expression of PLXNB2, BCL2 and cyclin D1, and reduced the expression of BAX.

Conclusion: In summary, we validated the high expression of circPLXNB2 and PLXNB2 in patients with AML. Elevated circPLXNB2 levels were associated with poor clinical outcomes in patients with AML. Importantly, circPLXNB2 accelerated tumour growth and progression, possibly by regulating PLXNB2 expression. Our study highlights the potential of circPLXNB2 as a new prognostic predictor and therapeutic target for AML in the future.
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http://dx.doi.org/10.1186/s12967-021-02793-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988933PMC
March 2021

The potential role of plasma fibroblast growth factor 21 as a diagnostic biomarker for abdominal aortic aneurysm presence and development.

Life Sci 2021 Jun 10;274:119346. Epub 2021 Mar 10.

Department of Vascular Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China. Electronic address:

Aims: Fibroblast growth factor 21 (FGF21) has been identified as the master hormonal regulator of energy balance, its elevation is observed in a series of metabolic and cardiovascular diseases. Studies have implicated the role of FGF21 signaling in the pathogenesis of abdominal aortic aneurysm (AAA). We will investigate the association of FGF21 and AAA development.

Materials And Methods: In this study, we assayed plasma levels of FGF21 in 82 patients with AAA and 44 control subjects, then analyzed their relationship with clinical, biochemical and histological phenotypes. The expression of β-klotho, an essential co-receptor of FGF21, was assessed with IHC staining and RT-qPCR. Machine learning models incorporate a combination of FGF21 and clinical data were utilized in the prediction of AAA occurrence.

Key Findings: FGF21 was statistically higher in patients with AAA (781 pg/ml [533, 1213]) than in control subjects (567 pg/ml [324, 939]). After adjustment for age and BMI, we found a positive association of FGF21 levels with AAA diameters, hypertension rate and hsCRP, and a negative correlation between FGF21 levels and HDL-c. Furthermore, the protein levels of β-klotho in abdominal aorta of AAA were found significantly lower than in control group indicating the presence of FGF21 resistance. Combining FGF21 levels with four clinical characteristics significantly improved the stratification of AAA and control groups with an AUC of 0.778.

Significance: Combining detection of plasma FGF21 and clinical characteristics may be reliable for identifying the presence of AAA. The role of FGF21 as a therapeutic target of AAA warrants further investigation.
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http://dx.doi.org/10.1016/j.lfs.2021.119346DOI Listing
June 2021

Zp4 is completely dispensable for fertility in female rats†.

Biol Reprod 2021 Jun;104(6):1282-1291

Institute of Reproductive & Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, China.

Zona pellucida (ZP), which is composed of at most four extracellular glycoproteins (ZP1, ZP2, ZP3, and ZP4) in mammals, shelters the oocytes and is vital in female fertility. Several studies have identified the indispensable roles of ZP1-3 in maintaining normal female fertility. However, the understanding of ZP4 is still very poor because only one study on ZP4-associated infertility performed in rabbits has been reported up to date. Here we investigated the function of mammalian Zp4 by creating a knockout (KO) rat strain (Zp4-/- rat) using CRISPR-Cas9-mediated DNA-editing method. The influence of Zp4 KO on ZP morphology and some pivotal processes of reproduction, including oogenesis, ovulation, fertilization, and pup production, were studied using periodic acid-Schiff's staining, superovulation, in vitro fertilization, and natural mating. The ZP morphology in Zp4-/- rats was normal, and none of these pivotal processes was affected. This study renewed the knowledge of mammalian Zp4 by suggesting that Zp4 was completely dispensable for female fertility.
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http://dx.doi.org/10.1093/biolre/ioab047DOI Listing
June 2021

Reduced Fracture Strength of 2D Materials Induced by Interlayer Friction.

Small 2021 Apr 9;17(13):e2005996. Epub 2021 Mar 9.

State Key Laboratory of Tribology, Department of Mechanical Engineering, Tsinghua University, Beijing, 100084, China.

The potential applications of 2D layered materials (2DLMs) as the functional membranes in flexible electronics and nano-electromechanical systems emphasize the role of the mechanical properties of these materials. Interlayer interactions play critical roles in affecting the mechanical properties of 2DLMs, and nevertheless the understanding of their relationship remains incomplete. In the present work, it is reported that the fracture strength of few-layer (FL) WS can be weakened by the interlayer friction among individual layers with the assistance of finite element simulations and density functional theory (DFT) calculations. The reduced fracture strength can be also observed in FL WSe but with a lesser extent, which is attributed to the difference in the interlayer sliding energies of WS and WSe as confirmed by DFT calculations. Moreover, the tip-membrane friction can give rise to the underestimation of the Young's modulus except for the membrane nonlinearity. These results give deep insights into the influence of interfacial interactions on the mechanical properties of 2DLMs, and suggest that importance should be also attached to the interlayer interactions during the design of nanodevices with 2DLMs as the functional materials.
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http://dx.doi.org/10.1002/smll.202005996DOI Listing
April 2021

Analysis of the primary presenting symptoms and hematological findings of COVID-19 patients in Bangladesh.

J Infect Dev Ctries 2021 03 7;15(2):214-223. Epub 2021 Mar 7.

Department of Gastroenterology, First affiliated hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P.R.China.

Introduction: SARS-Cov-2 infection or COVID-19 is a global pandemic. In this manuscript, we investigated the primary symptoms and basic hematological presentations of SARS-CoV-2 infection among the Bangladeshi patients.

Methodology: This was a multicentre cross-sectional study done on COVID-19 patients tested positive by RT PCR in Bangladesh. Clinical features of mild to moderate degree of COVID-19 patients; hematological and biochemical admission day laboratory findings of moderate to severe degree hospitalized COVID-19 patients were analyzed.

Results: COVID-19 patients in Bangladesh commonly presented with fever, cough, fatigue, shortness of breath, and sore throat. But symptoms like myalgia, diarrhea, skin rash, headache, Abdominal pain/cramp, nausea, vomiting, restlessness, and a higher temperature of >100°F have a greater presentation rate and more frequent than other published studies. CRP and Prothrombin time was found to increase in all the patients. Serum ferritin, ESR, SGPT, and D-Dimer were increased among 53.85%, 80.43, 44%, and 25% patients. 17.39% of the patients had leucocytosis and neutrophilia, 28.26% presented with lymphocytopenia, and 62.52% had mild erythrocytopenia. The difference between the decrease hemoglobin count (higher in the male) and increased SGPT (higher in female) against gender was significant.

Conclusions: Our study had evaluated a different expression in presenting symptoms of COVID-19 patients in Bangladesh. CRP, Prothrombin time, serum ferritin, ESR, SGPT, D-Dimer, erythrocytopenia, and lymphocytopenia can be assessments for diagnosis and prognosis of COVID-19 disease. Decrease hemoglobin count (higher in the male) and increased SGPT (higher in female) establish these two markers as a good candidate for diagnostic value against gender.
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http://dx.doi.org/10.3855/jidc.13692DOI Listing
March 2021

TWIST1 preserves hematopoietic stem cell function via the CACNA1B/Ca2+/mitochondria axis.

Blood 2021 May;137(21):2907-2919

State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences-Peking Union Medical College, Tianjin, China.

Mitochondria of hematopoietic stem cells (HSCs) play crucial roles in regulating cell fate and preserving HSC functionality and survival. However, the mechanism underlying HSC regulation remains poorly understood. Here, we identify transcription factor TWIST1 as a novel regulator of HSC maintenance through modulation of mitochondrial function. We demonstrate that Twist1 deletion results in significantly decreased lymphoid-biased HSC frequency, markedly reduced HSC dormancy and self-renewal capacity, and skewed myeloid differentiation in steady-state hematopoiesis. Twist1-deficient HSCs are more compromised in tolerance of irradiation- and 5-fluorouracil-induced stresses and exhibit typical phenotypes of senescence. Mechanistically, Twist1 deletion induces transactivation of voltage-gated calcium channel (VGCC) Cacna1b, which exhausts lymphoid-biased HSCs, impairs genotoxic hematopoietic recovery, and enhances mitochondrial calcium levels, metabolic activity, and reactive oxygen species production. Suppression of VGCC by a calcium channel blocker largely rescues the phenotypic and functional defects in Twist1-deleted HSCs under both steady-state and stress conditions. Collectively, our data, for the first time, characterize TWIST1 as a critical regulator of HSC function acting through the CACNA1B/Ca2+/mitochondria axis and highlight the importance of Ca2+ in HSC maintenance. These observations provide new insights into the mechanisms for the control of HSC fate.
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http://dx.doi.org/10.1182/blood.2020007489DOI Listing
May 2021

Characterizing the Structural Pattern of Heavy Smokers Using Multivoxel Pattern Analysis.

Front Psychiatry 2020 4;11:607003. Epub 2021 Feb 4.

Department of Radiology, Shenzhen University General Hospital, Shenzhen, China.

Smoking addiction is a major public health issue which causes a series of chronic diseases and mortalities worldwide. We aimed to explore the most discriminative gray matter regions between heavy smokers and healthy controls with a data-driven multivoxel pattern analysis technique, and to explore the methodological differences between multivoxel pattern analysis and voxel-based morphometry. Traditional voxel-based morphometry has continuously contributed to finding smoking addiction-related regions on structural magnetic resonance imaging. However, voxel-based morphometry has its inherent limitations. In this study, a multivoxel pattern analysis using a searchlight algorithm and support vector machine was applied on structural magnetic resonance imaging to identify the spatial pattern of gray matter volume in heavy smokers. Our proposed method yielded a voxel-wise accuracy of at least 81% for classifying heavy smokers from healthy controls. The identified regions were primarily located at the temporal cortex and prefrontal cortex, occipital cortex, thalamus (bilateral), insula (left), anterior and median cingulate gyri, and precuneus (left). Our results suggested that several regions, which were seldomly reported in voxel-based morphometry analysis, might be latently correlated with smoking addiction. Such findings might provide insights for understanding the mechanism of chronic smoking and the creation of effective cessation treatment. Multivoxel pattern analysis can be efficient in locating brain discriminative regions which were neglected by voxel-based morphometry.
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http://dx.doi.org/10.3389/fpsyt.2020.607003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890259PMC
February 2021

Catalytic degradation of dinotefuran by dielectric barrier discharge plasma combined with La-doping TiO.

Environ Technol 2021 Feb 3:1-11. Epub 2021 Feb 3.

School of Environmental Science and Engineering, Shandong University, Qingdao, People's Republic of China.

Degradation of neonicotinoid insecticide dinotefuran (DIN) in dielectric barrier discharge (DBD) non-thermal plasma combined with lanthanum-doped titanium dioxide (La-TiO) system was investigated. A La-TiO catalyst was prepared by the sol-gel method and characterized by SEM, XRD, and DRS. The effects of various factors (initial concentration, initial pH, input power, and addition of metal ions) on the removal rate of DIN were evaluated. The results indicated that when the initial concentration, input power, initial pH, and Fe catalyst ions were 100 mg/L, 150 W, 10.5 and 50 mg/L, respectively, the DIN degradation efficiency was improved to 99.0% by coupling 10 wt% La-TiO at 180 min. La-TiO showed excellent catalytic performance on DIN degradation in a DBD system. The removal rate decreased with the presence of HO and a scavenger, manifesting that plays an imperative role in the degradation process. Furthermore, intermediate products were analyzed by MS and the possible degradation pathway of DIN was proposed.
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http://dx.doi.org/10.1080/09593330.2021.1880488DOI Listing
February 2021

Deep Semantic Segmentation Feature-based Radiomics for the Classification Tasks in Medical Image Analysis.

IEEE J Biomed Health Inform 2020 Dec 8;PP. Epub 2020 Dec 8.

Recently, an emerging trend in medical image classification is to combine radiomics framework with deep learning classification network in an integrated system. Although this combination is efficient in some tasks, the deep learning-based classification network is often difficult to capture an effective representation of lesion regions, and prone to face the challenge of overfitting, leading to unreliable features and inaccurate results, especially when the sizes of the lesions are small or the training dataset is small. In addition, these combinations mostly lack an effective feature selection mechanism, which makes it difficult to obtain the optimal feature selection. In this paper, we introduce a novel and effective deep semantic segmentation feature-based radiomics (DSFR) framework to overcome the above-mentioned challenges, which consists of two modules: the deep semantic feature extraction module and the feature selection module. Specifically, the extraction module is utilized to extract hierarchical semantic features of the lesions from a trained segmentation network. The feature selection module aims to select the most representative features by using a novel feature similarity adaptation algorithm. Experiments are extensively conducted to evaluate our method in two clinical tasks: the pathological grading prediction in pancreatic neuroendocrine neoplasms (pNENs), and the prediction of thrombolytic therapy efficacy in deep venous thrombosis (DVT). Experimental results on both tasks demonstrate that the proposed method consistently outperforms the state-of-the-art approaches by a large margin.
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http://dx.doi.org/10.1109/JBHI.2020.3043236DOI Listing
December 2020

Preparation and electrochemical treatment application of Ti/Sb-SnO-Eu&rGO electrode in the degradation of clothianidin wastewater.

Chemosphere 2021 Feb 28;265:129126. Epub 2020 Nov 28.

School of Environmental Science and Engineering, Shandong University, Qingdao, 266237, China; Shandong Key Laboratory of Water Pollution Control and Resource Reuse, Qingdao, 266237, China. Electronic address:

This work investigated the preparation of Ti/Sb-SnO electrode co-doped with graphene and europium and the electrochemical degradation of clothianidin in aqueous solution with Ti/Sb-SnO-Eu&rGO electrode. The physicochemical properties of different electrodes were characterized by using the scanning electron microscopy, X-ray diffraction, oxygen evolution potential and cyclic voltammetry tests. The results indicated that the Ti/Sb-SnO-Eu&rGO electrodes have a compact structure and fine grain size and have a higher oxygen evolution overpotential than Ti/Sb-SnO-None, Ti/Sb-SnO-Eu and Ti/Sb-SnO-rGO electrodes. Among the four electrodes, the Ti/Sb-SnO-Eu&rGO electrode showed the highest efficiency and was chosen as the experimental electrode. The main influence factors on the degradation of clothianidin, such as initial pH, electrolyte concentration, current density and initial concentration of clothianidin, were analyzed. The results showed that the removal rate of clothianidin can reach 96.44% under the optimal conditions for 120 min treatment. Moreover, a possible degradation pathway including the fracture of internal bonds of clothianidin such as the N-N bond, the C-N bond that connects nitroguanidine to the thiazole ring and mineralization was elucidated by intermediate products identified by HPLC-MS method and Fourier transform infrared spectroscopy (FTIR). This paper introduces the Ti/Sb-SnO-Eu&rGO electrode into an electrocatalytic degradation system and could provide basic data and technique support and guidance for the clothianidin wastewater pollution control.
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http://dx.doi.org/10.1016/j.chemosphere.2020.129126DOI Listing
February 2021

The role of cystatin C as a proteasome inhibitor in multiple myeloma.

Hematology 2020 Dec;25(1):457-463

Department of Hematology, The Affiliated Hospital of Nantong University, Nantong, People's Republic of China.

Bone destruction and renal impairment are two frequent complications of multiple myeloma (MM). Cystatin C, an extracellular cysteine proteinase inhibitor, is encoded by the housekeeping gene CST3 and associated with human tumors. The role of cystatin C in multiple myeloma has been revealed recently. The purpose of this study was to explore the role of cystatin C as a proteasome inhibitor in multiple myeloma. A comprehensive literature review was conducted through Pubmed to summarize the published evidence on cystatin C in multiple myeloma. English literature sources since 1999 were searched, using the terms cystatin C, multiple myeloma. cystatin C is a sensitive indicator for the diagnosis of myeloma nephropathy and has a dual role in myeloma bone disease. Also, cystatin C reflects tumor burden and is strongly associated with prognosis in patients with multiple myeloma. Cystatin C have great diagnostic and prognostic value in multiple myeloma. It can provide a new treatment direction for MM by designing and searching for antagonists of cystatin C or cysteine protease agonists using cystatin C as a therapeutic target.
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http://dx.doi.org/10.1080/16078454.2020.1850973DOI Listing
December 2020

Genomic Profiling Comparison of Germline and Non- Carriers Reveals Amplification as a Risk Factor for Non- Carriers in Patients With Triple-Negative Breast Cancer.

Front Oncol 2020 30;10:583314. Epub 2020 Oct 30.

Department of Breast Surgery, Peking Union Medical College Hospital, Beijing, China.

Differences in genomic profiling and immunity-associated parameters between germline and non- carriers in TNBC with high tumor burden remain unexplored. This study aimed to compare the differences and explore potential prognostic predictors and therapeutic targets. The study cohort included 21 consecutive TNBC cases with germline mutations and 54 non- carriers with a tumor size ≥ 2 cm and/or ≥1 affected lymph nodes. Differences in clinicopathological characteristics and genomic profiles were analyzed through next-generation sequencing. Univariate Kaplan-Meier analysis and Cox regression model were applied to survival analysis. Immunohistochemistry was used to confirm the consistency between amplification and cyclin E1 protein overexpression. The cohort included 16 and five patients with germline and mutations, respectively. Patients with germline mutations were diagnosed at a significantly younger age and were more likely to have a family history of breast and/or ovarian cancer. Six non- carriers (11.11%) carried germline mutations in other cancer susceptibility genes, including five mutations in five homologous recombination repair (HRR) pathway genes (9.26%) and one mutation in (1.85%). Somatic mutations in HRR pathway genes were found in 22.22 and 14.29% of the non- and carriers, respectively. missense mutation ( = 0.046) and amplification ( = 0.2) were found only in the non- carriers. The median tumor mutation burden (TMB) was 4.1 Muts/Mb, whereas none of the cases had high microsatellite instability (MSI). status did not affect disease-free survival (DFS, = 0.15) or overall survival (OS, = 0.52). amplification was an independent risk factor for DFS in non- carriers with TNBC (HR 13.07, 95% CI 2.47-69.24, = 0.003). Consistency between amplification and cyclin E1 protein overexpression was confirmed with an AUC of 0.967 for cyclin E1 signal intensity. We found differences in genetic alterations between germline and non- carriers with TNBC and a high tumor burden. TMB and MSI may not be suitable predictors of TNBC for immune checkpoint inhibitors. Notably, amplification is a novel potential prognostic marker and therapeutic target for non- carriers with TNBC. Cyclin E1 may be used instead of to improve clinical applicability.
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http://dx.doi.org/10.3389/fonc.2020.583314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7662137PMC
October 2020

Synthesis of Ligustrazine from Acetaldehyde by a Combined Biological-Chemical Approach.

ACS Synth Biol 2020 11 6;9(11):2902-2908. Epub 2020 Nov 6.

Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China.

Ligustrazine is an important active alkaloid in medicine and in the food industry. Here, we developed a combined biological-chemical approach to produce ligustrazine from acetaldehyde. First, we constructed a whole-cell biocatalytic system to produce the precursor acetoin from acetaldehyde by overexpressing formolase (FLS). Second, a two-step strategy was developed to enhance protein expression of FLS by codon usage optimization at the first 14 codons and the introduction of an overlapping gene before the start codon. Through expression optimization and directed evolution of FLS, we improved the titer of acetoin about 40 fold when the concentration of acetaldehyde was 1.5 M. Finally, after reaction conditions optimization, the titer of acetoin and ligustrazine reached 222 g L and 94 g L, with a 86.5% and 48% conversion rate from acetaldehyde, respectively. The developed one-pot synthesis for acetoin and ligustrazine is expected to be applied to industrial production in the future with the advantages of a green process, high efficiency, and low cost.
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http://dx.doi.org/10.1021/acssynbio.0c00113DOI Listing
November 2020

Elevated Serum Tsukushi Levels in Patients With Hyperthyroidism.

Front Endocrinol (Lausanne) 2020 29;11:580097. Epub 2020 Sep 29.

Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Tsukushi (TSK) is a secreted hepatokine recently identified as playing an important role in modulating glucose and lipid metabolism, and systemic energy homeostasis. However, information is not available regarding the association between circulating TSK and hyperthyroidism in humans. We measured serum TSK levels in 180 patients with hyperthyroidism and 82 healthy controls recruited from the clinic. Of them, 46 hyperthyroid patients received thionamide treatment for 3 months. Hyperthyroid patients had higher levels of circulating TSK than healthy controls [186.67 (133.63-280.59) ng/ml vs. 97.27 (77.87-146.96) ng/ml, < 0.001]. Subjects with higher level of serum free triiodothyronine (T3) and free thyroxine (T4) had higher levels of circulating TSK. In addition, serum TSK levels markedly declined with the improvement of thyroid function after thionamide treatment. In multivariable linear regression analyses, circulating TSK concentrations were significantly associated with serum free T3, free T4, thyroid stimulating hormone, thyrotropin receptor antibody, total cholesterol, low-density lipoprotein cholesterol (LDL-cholesterol), high-density lipoprotein cholesterol (HDL-cholesterol), and basal metabolic rate (all < 0.01), adjusting for age, gender, smoking, and body mass index (BMI). Importantly, circulating TSK was significantly associated with risks of hyperthyroidism in multivariable logistic regression analyses, adjusting for age, gender, smoking, BMI, fasting glucose, LDL-cholesterol, and insulin resistance (HOMA-IR) [OR (95% CI), 1.012(1.005-1.019), = 0.001]. These findings indicate that circulating TSK concentrations are independently associated with hyperthyroidism, suggesting that circulating TSK may be a predictive factor of hyperthyroidism and can be used for therapeutic monitoring.
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http://dx.doi.org/10.3389/fendo.2020.580097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7553082PMC
June 2021

A low-intensity focused ultrasound-assisted nanocomposite for advanced triple cancer therapy: local chemotherapy, therapeutic extracellular vesicles and combined immunotherapy.

Biomater Sci 2020 Dec 27;8(23):6703-6717. Epub 2020 Oct 27.

The Second Affiliated Hospital of Chongqing Medical University & Chongqing Key Laboratory of Ultrasound Molecular Imaging, Chongqing, China.

Insufficient drug release and poor drug penetration compromise the efficacy of chemotherapy and hinder clinical translations in nanoparticle-based drug delivery systems. Inspired by the excretion process of exosomes, herein, silk fibroin-based doxorubicin preloaded calcium carbonates (CCs-SF/DOX) that integrate tumor-derived extracellular vesicle (EV) generation attributes are constructed for triple therapies of "local chemotherapy-therapeutic EVs-synergistic immunotherapy" (CT-EVs-IT). Assisted by low-intensity focused ultrasound, increased intracellular influx of CCs-SF/DOX can be achieved through acoustic pertubation-facilitated delivery or endocytic uptake. The acidic endosome or lysosome accelerates the release of DOX in the cancer cells for efficient cytotoxicity. Residual CCs-SF/DOX or uploaded DOX from dead/dying cells are encapsulated in vesicles and fuse with the plasma membrane of cells, triggering excretion of vesicles to extracellular space and responding to the acidic environment in the ECM, repeating the process infecting neighboring cancer cells, and exerting deep drug penetration based EV therapy. Meanwhile, CCs-SF/DOX scavenging of H promotes M1-like macrophage polarization, reversing immunosuppressive TME, and locally released chemotherapeutics potentiate antitumor immune response; both facilitate PD1/PD-L1 checkpoint blockade combined immunotherapy. Taken together, therapies of CT-EVs-IT assisted by LIFU contribute to achieve amplified antitumor benefits.
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http://dx.doi.org/10.1039/d0bm00804dDOI Listing
December 2020

A compound heterozygous mutation of the alkaline phosphatase ALPL gene causes hypophosphatasia in a Han Chinese family.

Exp Ther Med 2020 Dec 6;20(6):152. Epub 2020 Oct 6.

Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.

Hypophosphatasia (HPP) is a rare hereditary systemic disease that is characterized by defective bone and/or dental mineralization, and is caused by mutations in the alkaline phosphatase gene (ALPL). The present study investigated the ALPL mutation in a Chinese Han family with HPP and studied the pathogenesis of the mutations of the ALPL gene. DNA was extracted from peripheral venous blood of the family members. Sanger sequencing was used to screen the mutations. Associations between pathogenesis for both mutations were analyzed by bioinformatics, subcellular localization, measurement of enzyme activity and western blotting. Sanger sequencing revealed the compound heterozygous mutations c.203C>T (p.T68M) and c.571G>A (p.E191K). The mutations were located at exon 4 and 6 of the ALPL gene and were predicted by Polyphen-2 analysis to be harmful. Protein analysis indicated a decrease in mature protein production and lower enzyme activity in 293T cells transfected with plasmids carrying the mutations. The ALPL gene was cloned into the pcDNA3.1(+) vector and mutant plasmids ALPL-pT68M and ALPL-pE191K were constructed. Immunofluorescence observed in cells transfected with the ALPL-pE191K mutant plasmid was mainly located in the cell membrane. However, staining in the cytoplasm was increased compared with the wild type, and almost no fluorescence was identified in 293T cells transfected with the ALPL-pT68M mutant plasmid. The present findings demonstrated that the compound heterozygous c.571G>A and c.203C>T mutations may contribute to childhood HPP by resulting in mislocalization, decreased protein expression and loss of enzyme activity in a Han Chinese family. The results of the current study may provide insights into the potential molecular mechanism of HPP.
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http://dx.doi.org/10.3892/etm.2020.9281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571384PMC
December 2020

Effects of ex vivo ischemia time and delayed processing on quality of specimens in tissue biobank.

Mol Med Rep 2020 Nov 10;22(5):4278-4288. Epub 2020 Sep 10.

Clinical Biobank, Department of Medical Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, P.R. China.

The RNA quality of tissue biobank is crucial for translational research; however, the effects of the ex vivo ischemia time on RNA integrity and expression of genes related to hypoxia, stress, apoptosis and autophagy remains elusive. A total of 18 carcinoma tissues were stored at room temperature for 15 min, 30 min, 1, 2, 4, 8 and 24 h. The integrity and purity of isolated RNA were analyzed. Furthermore, the gene expression of mTOR, hypoxia‑inducible factor 1α, phosphatidylinositol 4,5‑bisphosphate 3‑kinase catalytic subunit β isoform (PI3KCB), threonine kinase 1 (AKT1), NF‑κB, protein kinase AMP‑activated catalytic subunit α1 (AMPKα1), caspase 8 (CASP8), unc‑51 like autophagy activating kinase 1 and Fas cell surface death receptor were analyzed using reverse transcription‑quantitative PCR. The results demonstrated that RNA integrity numbers (RINs) remained stable in carcinoma tissues following ex vivo ischemia for 2 h at room temperature and that degradation began at 4 h (P<0.001). Additionally, the expression of PI3KCB, AKT1, AMPKα1 and CASP8 decreased at time points 8‑24 h following ex vivo ischemia and delayed processing (P<0.001). In conclusion, >2 h of ex vivo ischemia and delayed processing induced RNA degradation and RIN, and the gene expressions of PI3KCB, AKT, AMPKα1 and CASP8 may be considered as markers to evaluate tissue quality at the gene expression level, providing a method for the standard processing and assessment of tissue specimen.
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http://dx.doi.org/10.3892/mmr.2020.11503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533433PMC
November 2020

PM2.5-induced pulmonary inflammation via activating of the NLRP3/caspase-1 signaling pathway.

Environ Toxicol 2021 Mar 30;36(3):298-307. Epub 2020 Sep 30.

Department of Respiratory and Critical Care Medicine, Central Hospital Affiliated to Shenyang Medical College, Shenyang, China.

Particulate matter 2.5 (PM2.5)-induced pulmonary inflammation has become a public concern in recent years. In which, the activation of the NLRP3/caspase-1 pathway was closely related to the inflammatory response of various diseases. However, the promotion effect of the NLRP3/caspase-1 pathway on PM2.5-induced pulmonary inflammation remains largely unclear. Here, our data showed that PM2.5 exposure caused lung injury in the mice by which inflammatory cell infiltration occurred in lung and alveolar structure disorder. Meanwhile, the exposure of human bronchial epithelial cells (16HBE) to PM2.5 resulted in suppressed cell viability, as well as elevated cell apoptosis. Moreover, a higher level of inflammatory cytokine and activation of the NLRP3/caspase-1 pathway in PM2.5-induced inflammation mice models and 16HBE cells. Mechanistically, pretreatment with MCC950, a NLRP3/caspase-1 pathway inhibitor, prevented PM2.5-induced lung injury, inflammatory response, and the number of inflammatory cells in BALFs, as well as promoted cell viability and decreased inflammatory cytokine secretion. Collectively, our findings indicated that the NLRP3/caspase-1 pathway serves a vital role in the pathological changes of pulmonary inflammation caused by PM2.5 exposure. MCC950 was expected to be the therapeutic target of PM2.5 inhalation mediated inflammatory diseases.
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http://dx.doi.org/10.1002/tox.23035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891361PMC
March 2021

LncRNA SNAI3-AS1 promotes PEG10-mediated proliferation and metastasis via decoying of miR-27a-3p and miR-34a-5p in hepatocellular carcinoma.

Cell Death Dis 2020 08 11;11(8):685. Epub 2020 Aug 11.

Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, 710061, Xi'an, Shaanxi, P. R. China.

During recent years, long noncoding RNAs (lncRNAs) have received focal attention due to their important function in cancer regulation. Though the relation between lncRNA SNAI3-AS1 and the development of hepatocellular carcinoma (HCC) has been described in our previous study, the role and the exact mechanism of SNAI3-AS1 are still unclear. In this study, qRT-PCR analysis revealed that the expression of SNAI3-AS1 was elevated and was correlated with the levels of PEG10 in HCC tissues. Through functional experiments, we determined that knockdown of SNAI3-AS1 and PEG10 inhibited the proliferation and metastasis, whereas overexpression of SNAI3-AS1 and PEG10 promoted the proliferation and metastasis of HCC cells. In addition, rescue experiments confirmed that upregulation of PEG10 partially restored cell function inhibition induced by SNAI3-AS1 knockdown. Therefore, we hypothesized that PEG10 may be regulated by SNAI3-AS1, which in turn mediates the malignant biological processes of HCC cells regulated by PEG10. Further bioinformatics analysis and mechanistic experiments showed that SNAI3-AS1 functions as a competing endogenous RNA (ceRNA) to activate PEG10 by acting as a sponge for miR-27-3p and miR-34a-5p. In summary, our study revealed that SNAI3-AS1 is a tumor regulator of PEG10 in the progression of HCC, and may contribute to the improvement of HCC diagnosis and therapy.
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http://dx.doi.org/10.1038/s41419-020-02840-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442791PMC
August 2020