Publications by authors named "Qiang Han"

159 Publications

HLA-A2.1-restricted ECM1-derived epitope LA through DC cross-activation priming CD8 T and NK cells: a novel therapeutic tumour vaccine.

J Hematol Oncol 2021 Apr 28;14(1):71. Epub 2021 Apr 28.

Department of Pharmacology, School of Pharmacy, China Medical University, No. 13, Beihai Road, Dadong District, Shenyang, Liaoning Province, China.

Background: CD8 T cell-mediated adaptive cellular immunity and natural killer (NK) cell-mediated innate immunity both play important roles in tumour immunity. This study aimed to develop therapeutic tumour vaccines based on double-activation of CD8 T and NK cells.

Methods: The immune Epitope database, Molecular Operating Environment software, and enzyme-linked immunosorbent assay were used for epitope identification. Flow cytometry, confocal microscopy, UPLC-QTOF-MS, and RNA-seq were utilized for evaluating immunity of PBMC-derived DCs, CD8 T or NK cells and related pathways. HLA-A2.1 transgenic mice combined with immunologically reconstituted tumour-bearing mice were used to examine the antitumour effect and safety of epitope vaccines.

Results: We identified novel HLA-A2.1-restricted extracellular matrix protein 1(ECM1)-derived immunodominant epitopes in which LA induced a potent immune response. We also found that LA-loaded DCs upregulated the frequency of CD3/CD8 T cells, CD45RO/CD69 activated memory T cells, and CD3/CD16/CD56 NK cells. We demonstrated cytotoxic granule release of LA/DC-CTLs or LA/DC-NK cells and cytotoxicity against tumour cells and microtissue blocks via the predominant IFN-γ/perforin/granzyme B cell death pathway. Further investigating the mechanism of LA-mediated CD8 T activation, we found that LA could be internalized into DCs through phagocytosis and then formed a LA-MHC-I complex presented onto the DC surface for recognition of the T cell receptor to upregulate Zap70 phosphorylation levels to further activate CD8 T cells by DC-CTL interactions. In addition, LA-mediated DC-NK crosstalk through stimulation of the TLR4-p38 MAPK pathway increased MICA/B expression on DCs to interact with NKG2D for NK activation. Promisingly, LA could activate CD8 T cells and NK cells simultaneously via interacting with DCs to suppress tumours in vivo. Moreover, the safety of LA was confirmed.

Conclusions: LA-induced immune antitumour activity through DC cross-activation with CD8 T and NK cells, which demonstrated proof-of-concept evidence for the capability and safety of a novel therapeutic tumour vaccine.
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http://dx.doi.org/10.1186/s13045-021-01081-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082934PMC
April 2021

WBP2 negatively regulates the Hippo pathway by competitively binding to WWC3 with LATS1 to promote non-small cell lung cancer progression.

Cell Death Dis 2021 Apr 9;12(4):384. Epub 2021 Apr 9.

Department of Pathology, College of Basic Medical Sciences and the First Affiliated Hospital of China Medical University, Shenyang, China.

WW domain binding protein-2 (WBP2) can function as a Yes-associated protein/transcriptional co-activator with PDZ-binding motif (YAP/TAZ) co-activator and has a crucial role in promoting breast cancer progression. However, the expression and potential molecular mechanisms of WBP2 in the context of lung cancer are not fully understood. We determined that WBP2 was highly expressed in lung cancer specimens and cell lines and that this expression was closely related to the advanced pTNM stage, lymph node metastasis, and poor prognosis of patients. In addition, gain- and loss-of-function experiments revealed that WBP2 could significantly promote the proliferation and invasion of lung cancer cells both in vivo and in vitro. To elucidate the underlying molecular mechanism, we determined that wild-type WBP2 could competitively bind to the WW domain of WWC3 (WW and C2 domain-containing-3) with LATS1 (Large tumor suppressor-1) through its PPxY motifs, thus inhibiting the formation of the WWC3-LATS1 complex, reducing the phosphorylation level of LATS1, suppressing the activity of the Hippo pathway, and ultimately promoting YAP nuclear translocation. Therefore, from the aspect of upstream molecules of Hippo signaling, WBP2 promotes the malignant phenotype of lung cancer cells in a unique manner that is not directly dependent upon YAP, thus providing a corresponding experimental basis for the development of targeted therapeutic drugs for lung cancer.
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http://dx.doi.org/10.1038/s41419-021-03600-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035140PMC
April 2021

Ferulic acid alleviates lipotoxicity-induced hepatocellular death through the SIRT1-regulated autophagy pathway and independently of AMPK and Akt in AML-12 hepatocytes.

Nutr Metab (Lond) 2021 Jan 19;18(1):13. Epub 2021 Jan 19.

College of Basic Medicine and Public Health, Zhejiang Chinese Medical University, Hangzhou, 310053, China.

Background: Lipotoxicity-induced cell death plays a detrimental role in the pathogenesis of metabolic diseases. Ferulic acid, widespread in plant-based food, is a radical scavenger with multiple bioactivities. However, the benefits of ferulic acid against hepatic lipotoxicity are largely unclear. Here, we investigated the protective effect of ferulic acid against palmitate-induced lipotoxicity and clarified its potential mechanisms in AML-12 hepatocytes.

Methods: AML-12 mouse hepatocytes were exposed to palmitate to mimic lipotoxicity. Different doses (25, 50, and 100 μM) of ferulic acid were added 2 h before palmitate treatment. Cell viability was detected by measuring lactate dehydrogenase release, nuclear staining, and the expression of cleaved-caspase-3. Intracellular reactive oxygen species content and mitochondrial membrane potential were analysed by fluorescent probes. The potential mechanisms were explored by molecular biological methods, including Western blotting and quantitative real-time PCR, and were further verified by siRNA interference.

Results: Our data showed that ferulic acid significantly inhibited palmitate-induced cell death, rescued mitochondrial membrane potential, reduced reactive oxygen species accumulation, and decreased inflammatory factor activation, including IL-6 and IL-1beta. Ferulic acid significantly stimulated autophagy in hepatocytes, whereas autophagy suppression blocked the protective effect of ferulic acid against lipotoxicity. Ferulic acid-activated autophagy, which was triggered by SIRT1 upregulation, was mechanistically involved in its anti-lipotoxicity effects. SIRT1 silencing blocked most beneficial changes induced by ferulic acid.

Conclusions: We demonstrated that the phytochemical ferulic acid, which is found in plant-based food, protected against hepatic lipotoxicity, through the SIRT1/autophagy pathway. Increased intake of ferulic acid-enriched food is a potential strategy to prevent and/or improve metabolic diseases with lipotoxicity as a typical pathological feature.
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http://dx.doi.org/10.1186/s12986-021-00540-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814733PMC
January 2021

Designed Fabrication of Polymer-Mediated MOF-Derived Magnetic Hollow Carbon Nanocages for Specific Isolation of Bovine Hemoglobin.

ACS Biomater Sci Eng 2020 03 17;6(3):1387-1396. Epub 2020 Feb 17.

Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, P. R. China.

It is highly required to develop well-designed separation materials for the specific isolation of certain proteins in proteomic research. Herein, the new type of metal-organic framework (MOF)-derived polymer-mediated magnetic hollow nanocages was fabricated via stress-induced orientation contraction, which was further applied for specific enrichment of proteins. The core-shell nanocomposites comprised of polymer-mediated ZIF-67 cores and polydopamine (PDA) shells, after annealing, generated magnetic hollow carbon nanocages with hierarchical pores and structures. Particularly, the magnetic carbonized PDA@F127/ZIF-67 hollow nanocages exhibited a remarkable adsorption capacity toward bovine hemoglobin (BHB) up to 834.3 mg g, which was significantly greater than that of the directed carbonized ZIF-67 nanoparticles. The results also exhibited the notable specificity of the obtained nanocages on complex biosamples, including intact mixed proteins and fetal calf serum. The hierarchically hollow porous structure greatly improves the specific surface area and reduces the mass transfer resistance, leading to enhanced high adsorption for target protein BHB. This novel method will be promising for the applications in purification and enrichment of biomacromolecules for complex biosamples, which successfully solve the problem of low adsorption efficiency and tedious separating process of the previous MOF-derived materials.
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http://dx.doi.org/10.1021/acsbiomaterials.9b01793DOI Listing
March 2020

[Mechanisms of Huanshao Capsules protecting the reproductive function in rats with ornidazole-induced asthenozoospermia].

Zhonghua Nan Ke Xue 2020 May;26(5):446-451

Department of Andrology, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing 100091, China.

Objective: To explore the possible mechanism of Huanshao Capsules (HSC) protecting the reproductive function in rats with ornidazole-induced asthenozoospermia (AZS).

Methods: Forty SD male rats were randomly divided into four groups of equal number, blank control, AZS model control, HSC and L-carnitine (LC) intervention. The AZS model was established in the latter three groups of rats by intragastrical administration of ornidazole at 400 mg/kg/d for 28 days, and meanwhile the animals in the HSC and LC groups were treated by gavage of HSC at 0.31 g/kg/d and LC at 100 mg/kg/d, respectively. Then, all the rats were killed for examination of the LC content, sperm concentration, sperm motility and expression of OCTN2 mRNA in the epididymis and observation of the histopathological changes in the testis tissue.

Results: Compared with the AZS model controls, the rats in the HSC and LC groups showed significantly increased LC content (2 880.3 vs 6 366.5 and 6 934.7 mg/L, P < 0.01), sperm concentration ([34.58 ± 10.25] vs [46.19 ± 14.23] and [42.25 ± 6.11] ×10⁶/ml, P < 0.01), sperm motility ([42.59 ± 7.54]% vs [61.34 ± 7.98]% and [61.34 ± 7.98]%, P < 0.01) and expression of OCTN2 mRNA in the epididymis (26.07% vs 27.26% and 27.15%, P < 0.01). The animals of the HSC group exhibited a higher comparability than those of the LC group to the blank controls in the morphology, arrangement and activity of spermatogenic cells.

Conclusions: HSC can protect the reproductive function and improve sperm concentration and motility in the model rats with ornidazole-induced AZS, which may be associated with its abilities of up-regulating the expression of OCTN2 mRNA and increasing the LC content in the epididymis.
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May 2020

Molecular Mechanism of Slow Vegetative Growth in Tetraploid.

Genes (Basel) 2020 Nov 27;11(12). Epub 2020 Nov 27.

Beijing Advanced Innovation Center for Tree Breeding by Molecular Design, National Engineering Laboratory for Tree Breeding, College of Biological Sciences and Technology, Beijing Forestry University, Beijing 100083, China.

Tetraploid plants often have altered rates of vegetative growth relative to their diploid progenitors. However, the molecular basis for altered growth rates remains a mystery. This study reports microRNA (miRNA) and gene expression differences in tetraploids and counterpart diploids using RNA and miRNA sequencing. The results showed that there was no significant difference between young leaves in the expression of vegetative growth-related miRNAs. However, as leaves aged, the expression of auxin- and gibberellin-related miRNAs was significantly upregulated, while the expression of senescence-related miRNAs was significantly downregulated. The dose effect enhanced the negative regulation of the target genes with , , , and being downregulated, and and being upregulated. As a result, the chloroplast degradation of tetraploid leaves was accelerated, the photosynthetic rate was decreased, and the synthesis and decomposition ability of carbohydrate was decreased.
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http://dx.doi.org/10.3390/genes11121417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761321PMC
November 2020

Safety and efficacy of traditional Chinese medicine, Qiaoshao formula, combined with dapoxetine in the treatment of premature ejaculation: An open-label, real-life, retrospective multicentre study in Chinese men.

Andrologia 2021 Feb 24;53(1):e13915. Epub 2020 Nov 24.

Chair of Endocrinology and Medical Sexology (ENDOSEX), Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.

To evaluate the safety and efficacy of Chinese medicine, Qiaoshao formula combined with dapoxetine was used for the treatment of premature ejaculation in a real-life setting. Nine hundred and five males diagnosed with premature ejaculation were reviewed in this retrospective cohort study. We divided the patients into two groups: dapoxetine alone and Qiaoshao formula combined with dapoxetine according to actual interventions provided to patients in clinics. The perceived intravaginal ejaculation latency time and the premature ejaculation profile measures markedly improved in both groups. However, in men with severe premature ejaculation (baseline perceived intravaginal ejaculation latency time <1 min) and those with baseline age ≤30 years, the perceived intravaginal ejaculation latency time was slightly but significantly longer with combined therapy than with dapoxetine alone (p < .05). Therefore, combined therapy involving the Qiaoshao formula and dapoxetine proved to safe as well as effective for treating premature ejaculation while prolonging the perceived intravaginal ejaculation latency time, which significantly improved the overall satisfaction of the patient and likely that of the couple.
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http://dx.doi.org/10.1111/and.13915DOI Listing
February 2021

NAD(P)-dependent steroid dehydrogenase-like protein and neutral cholesterol ester hydrolase 1 serve as novel markers for early detection of gastric cancer identified using quantitative proteomics.

J Clin Lab Anal 2021 Feb 21;35(2):e23652. Epub 2020 Nov 21.

Department of Biochemistry, School of Preclinical Medicine, North Sichuan Medical College, Nanchong, China.

Background: Gastric cancer (GC) is the third most common cause of cancer deaths worldwide. In the present study, we aimed to identify novel GC biomarkers by integrating isobaric tags of relative and absolute quantitation (iTRAQ) for aberrantly expressed proteins in GC patients.

Methods: Using stable isotope tags, we labeled an initial discovery group comprising four paired gastric cancer and adjacent gastric tissue samples, and subjected them to LC-ESI-MS/MS. We used a validation set comprising 129 paired gastric cancer and adjacent gastric tissues from patients and benign healthy controls to validate the candidate targets.

Results: We identified two proteins, NAD(P)-dependent steroid dehydrogenase-like (NSDHL) and neutral cholesterol ester hydrolase 1 (NCEH1), that were significantly overexpressed in GC tissues. The sensitivity and specificity of NSDHL were 80.6% and 74.4%, respectively, in GC compared with a sensitivity of 25.6% in adjacent tissues and 24% in benign healthy controls. The area under the ROC curve (AUC) for NSDHL was 0.810 for GC detection. Overexpression of NSDHL in GC was significantly correlated with local tumor invasion. The sensitivity and specificity of NCEH1 were 77.5% and 73.6%, respectively, in GC compared with a sensitivity of 26.4% in adjacent tissues and 20% in benign controls. The AUC for NSDHL was 0.792. Overexpression of NCEH1 was significantly associated with tumor histological classification and local invasion. Moreover, a combined analysis of NSDHL and NCEH1 achieved a sensitivity and specificity of 85.7% and 83%, respectively, and the AUC was 0.872. The combined analysis of NSDHL and NCEH1 was significantly correlated with histological grade and TNM Ⅱ-Ⅳ staging.

Conclusions: iTRAQ-labeled quantitative proteomics represents a powerful method to identify novel cancer biomarkers. The present study identified NSDHL and NCEH1 as useful biomarkers for screening, diagnosis, and prognosis of patients with gastric cancer.
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http://dx.doi.org/10.1002/jcla.23652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891516PMC
February 2021

Effect of Lignin Content on Properties of Flexible Transparent Poplar Veneer Fabricated by Impregnation with Epoxy Resin.

Polymers (Basel) 2020 Nov 5;12(11). Epub 2020 Nov 5.

College of Materials Science and Engineering, Nanjing Forestry University, Nanjing 210037, China.

In this work, poplar veneer (PV) rotary-cut from fast-growing polar was delignified to prepare flexible transparent poplar veneer (TPV). Lignin was gradually removed from the PV and then epoxy resin filled into the delignified PV. The study mainly concerns the effect of lignin content on microstructure, light transmittance, haze, tensile strength, and thermal stability of the PVs impregnated with epoxy resin. The results indicate that the lignin could be removed completely from the PV when the delignification time was around 8 h, which was proved by FTIR spectra and chemical component detection. Moreover, according to SEM observation and XRD testing, the porosity and crystallinity of the PVs were gradually increased with the removal of lignin. Also, the optical properties measurement indicated that the light transmittance and haze of the TPVs gradually increased, and the thermal stability also became more stable as shown by thermogravimetric analysis (TG). However, the tensile strength of the TPVs declined due to the removal of lignin. Among them, TPV exhibited excellent optical properties, thermal stability, and tensile strength. Consequently, it has great potential to be used as a substrate in photovoltaics, solar cells, smart windows, etc.
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http://dx.doi.org/10.3390/polym12112602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694516PMC
November 2020

Construction of a breeding parent population of Populus tomentosa based on SSR genetic distance analysis.

Sci Rep 2020 10 29;10(1):18573. Epub 2020 Oct 29.

Advanced Innovation Center for Tree Breeding by Molecular Design, Beijing Forestry University, Beijing, 100083, China.

Parent selection is the core of hybrid breeding. The breeding strategy involving the parental identification of superior open-pollinated progeny of Populous tomentosa germplasm resources can significantly improve the efficiency of parental matching. However, due to some factors such as loose powdering time and pollen competitiveness, the offspring derived from open-pollination families which do not undergo completely random mating. Although hybrid combinations based on the male identification method have a high combining ability, this method cannot easily cover the mating combinations of all male and female specimens in the germplasm bank. In addition, the performance of superior plants in open-pollinated families also affects the selection result. If the trait performance value is higher than the population average, then the special combining ability of the reconstructed hybrid combination may be overestimated. Obtaining a solution to the above problems is of great significance for improving the efficiency and accuracy of selecting hybrid parents of P. tomentosa. In this study, 24 pairs of SSR (Simple Sequence Repeats) molecular markers were used to analyze the genetic differentiation of P. tomentosa germplasm resources. The results showed that the genetic variation of the P. tomentosa population was derived from individuals within the provenance, indicating that high genetic diversity is preserved in provenances. The correlation analysis showed that there was a significant positive correlation between the special combining ability of planting height and diameter at breast height (dbh) of the 34 full-sib progeny population and the genetic distance between the parents. Then, the genetic distance between 18 female plants with high fertility and 68 male plants with large pollen quantity was analyzed using this correlation. Fifteen female parents and 12 male parents were screened out, and 52 hybrid combinations with high specific combining ability for growth traits were predicted. Furthermore, for the male parent identification of superior individual plants, we constructed the breeding parent population including 10 female parents and 5 male parents, generating 14 hybrid combinations with potentially high combining ability. The results of the hybridization test showed that the specific combining ability of plant height and dbh was significantly higher than the controlled pollination. Moreover, genetic distance and paternal identification can be used to rapidly and efficiently construct hybrid parent combinations and breeding parent populations.
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http://dx.doi.org/10.1038/s41598-020-74941-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596703PMC
October 2020

Genomic Study of Chinese Quadruple-negative GISTs Using Next-generation Sequencing Technology.

Appl Immunohistochem Mol Morphol 2021 01;29(1):34-41

Department of Pathology, the First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, People's Republic of China.

Purpose: Approximately 10% of gastrointestinal stromal tumors (GISTs) are devoid of KIT, PDGFRA (platelet-derived growth factor-alpha), BRAF, and SDH alterations. The aim of this study was to characterize molecular drivers in Chinese patients with quadruple-negative GISTs.

Patients And Methods: In 1022 Chinese patients with GIST, mutations of KIT and PDGFRA were analyzed by direct sequencing. Of these mutations, 142 KIT/PDGFRA wild-type (WT) GISTs were detected, and succinate dehydrogenase (SDH) deficiency was determined using immunohistochemistry analysis of succinate dehydrogenase B. In 78 KIT/PDGFRA/SDH cases, we performed targeted 425 cancer-related gene analysis using next-generation sequencing. The correlation between molecular findings and clinicopathologic features was also analyzed.

Results: We defined 72 quadruple-negative GISTs from enrollments. They featured nongastric localization with histologic characteristics of spindle cells and male predilection. An overall 27.78% (20/72) of quadruple-negative tumors carried TP53, and 25.00% (18/72) carried RB1 mutations, which were frequently associated with high mitotic index and large size. TP53 analyses demonstrated coexistence with mutational activation of other oncogenes in 12 of 20 cases. A total of 18 RB1-mutated cases were independent of TP53. Further, no tumors carried NF1 and BRAF mutations.

Conclusions: We report the genomic analysis of Chinese quadruple-negative patients. These databases may help advance our understanding of quadruple-negative GISTs' progression. Next-generation sequencing from GISTs is feasible to provide relevant data for guiding individualized therapy.
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http://dx.doi.org/10.1097/PAI.0000000000000842DOI Listing
January 2021

A zwitterionic hydrogel coated titanium surface with high-efficiency endothelial cell selectivity for rapid re-endothelialization.

Biomater Sci 2020 Oct 3;8(19):5441-5451. Epub 2020 Sep 3.

Department of Biochemical Engineering, Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (MOE), School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300350, China.

Coronary stent implantation is an effective procedure for percutaneous coronary intervention treatment. However, its long-term safety and efficacy are still hindered by the in-stent restenosis and late thrombus formation. Herein, an anti-biofouling and endothelial cell selective zwitterionic hydrogel coating was developed to simultaneously enhance the nonspecific resistance and rapid re-endothelialization of the titanium surface. An endothelial cell selective peptide, REDV, could be simply conjugated on the zwitterionic carboxybetaine (CB) hydrogel to prepare the REDV/CB coating. It was found that the REDV/CB hydrogel layer maintained antifouling properties, which could inhibit the protein adsorption, bacterial adhesion, platelet activation and aggregation, and smooth muscle cell proliferation. More importantly, the co-culture study confirmed that the conjugated REVD peptide could specifically capture endothelial cells and promote their migration and proliferation, and simultaneously decrease the adhesion and proliferation of smooth muscle cells. Therefore, the antifouling and endothelial cell selective coating proposed in this work provides a promising strategy to develop an intravascular stent for promoted re-endothelialization and inhibited neointimal hyperplasia in clinical applications.
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http://dx.doi.org/10.1039/d0bm00671hDOI Listing
October 2020

Applications of Micro-Indentation Technology to Estimate Fracture Toughness of Shale.

Materials (Basel) 2020 Sep 22;13(18). Epub 2020 Sep 22.

College of petroleum engineering, Xi'an Shiyou University, Xi'an 710065, China.

The fracture toughness of shale is a basic parameter that can provide effective theoretical support for wellbore stability and hydraulic fracturing of a shale reservoir. Due to the composition and microstructure, there are many problems in evaluating the mechanical properties of shale in a macroscopic test. In this paper, the composition and pore distribution of shale were studied by X-ray diffraction and nuclear magnetic resonance. Scanning electron microscopy was used to characterize the pore structure. The setting of experimental parameters and the selection of the indenter were discussed. Micro-indentation technique was proposed and applied to fracture toughness analysis of shale. The results show that Berkovich indenter is more suitable for shale indentation test than Vickers indenter. Fracture toughness of shale indentation is obviously affected by surface roughness and indentation position. Fracture toughness of shale decreases slightly with the increase of the indentation load. The energy analysis result presents that the effect of cracking on the ratio of total/unloading work is minimal when there is no significant stripping on the shale surface. Compared with the experimental method, energy methods can obtain all the analysis parameters from a single indentation test. The results of comparative analysis with macroscopic experiments display that micro-indentation test can effectively predict the macroscopic fracture toughness of shale.
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http://dx.doi.org/10.3390/ma13184208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7560459PMC
September 2020

Downregulation of m A reader YTHDC2 promotes tumor progression and predicts poor prognosis in non-small cell lung cancer.

Thorac Cancer 2020 11 21;11(11):3269-3279. Epub 2020 Sep 21.

Department of Respiratory and Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin, China.

Background: m A modification affects the pathological progress of many diseases by affecting RNA stability and translocation. YTHDC2, a m A reader, is associated with multiple cancers; however, little is known of its role in non-small cell lung cancer (NSCLC).

Methods: The GEPIA, Oncomine and GEO databases were analyzed to assess expression of YTHDC2 in NSCLC patients. Quantitative polymerase chain reaction, western blot and immunohistochemistry were used to detect YTHDC2 expression in different NSCLC cell lines (H1299, H460, H292 and A549) and patients. The effects of YTHDC2 on NSCLC cell lines (A549 and H1299) proliferation and migration were employed using CCK8 and transwell assays. The potential target RNAs of YTHDC2 were obtained from the POSTAR database. Functional enrichment analysis of YTHDC2 targeted RNAs was performed using the Metascape database.

Results: GEPIA, Oncomine and GEO databases showed low expression of YTHDC2 in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) patients. YTHDC2 expression was significantly decreased in different NSCLC cell lines and our clinical samples. Moreover, low expression of YTHDC2 was significantly associated with poor differentiation, lymph node metastasis, tumor size and stage. In addition, YTHDC2 could suppress the proliferation and migration ability of A549 and H1299 cell lines. Kaplan-Meier Plotter database analysis revealed that patients with low level of YTHDC2 had a significantly poor prognosis. Finally, functional enrichment analysis of YTHDC2 targeted RNAs indicated several enriched pathways related to cancer.

Conclusions: These findings elucidate that YTHDC2 suppresses tumorigenesis in NSCLC, indicating that YTHDC2 may be a promising therapeutic target for NSCLC.

Key Points: SIGNIFICANT FINDINGS OF THE STUDY: This study demonstrated that the downregulation of YTHDC2 promotes tumor progression and predicts poor prognosis in non-small cell lung cancer (NSCLC).

What This Study Adds: YTHDC2 might be a promising therapeutic target for non-small cell lung cancer (NSCLC).
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http://dx.doi.org/10.1111/1759-7714.13667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606000PMC
November 2020

WW and C2 domain-containing protein-3 promoted EBSS-induced apoptosis through inhibiting autophagy in non-small cell lung cancer cells.

J Thorac Dis 2020 Aug;12(8):4205-4215

Department of Pathology, the First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, China.

Background: WW and C2 domain-containing protein-3 (WWC3) was identified in our previous studies as a tumor suppressor gene, which inhibits the proliferation and invasiveness of lung cancer cells. However, the relationship between WWC3 and autophagy and apoptosis in lung cancer cells is unclear. In this study, we aimed to investigate the potential role of WWC3 in starvation-induced autophagy and apoptosis in non-small cell lung carcinoma (NSCLC) cells.

Methods: The immunoblotting assay and quantitative real-time polymerase chain reaction (RT-qPCR) were used for observing the change of WWC3 protein and mRNA level under starvation condition. The immunoblotting assay and immunofluorescence assay were performed to detect the impact of WWC3 expression on autophagy process induced by Earle's balanced salt solution (EBSS) in lung cancer cells; APC/propidium iodide (PI) apoptosis assay, caspase-3/7 activity assay and MTT assay were used for the apoptosis and proliferation detection of lung cancer cells.

Results: After starvation had been induced with EBSS, WWC3 expression was significantly decreased in the NSCLC cells. Ectopic WWC3 expression weakened the autophagy process in a Beclin1-independent manner and promoted non-small cell lung cancer cell apoptosis via EBSS starvation. Moreover, the inhibition of WWC3 gene knockout was weakened by 3-methyladenine (3-MA), an autophagy inhibitor.

Conclusions: These results indicate that WWC3 promotes apoptosis and death of starved lung cancer cells, at least partly through autophagy.
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http://dx.doi.org/10.21037/jtd-20-966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7475589PMC
August 2020

A nomogram based on a patient-reported outcomes measure: predicting the risk of readmission for patients with chronic heart failure.

Health Qual Life Outcomes 2020 Aug 27;18(1):290. Epub 2020 Aug 27.

Department of Health Statistics, School of Public Health, Shanxi Medical University, 56 South XinJian Road, Taiyuan, 030001, Shanxi Province, China.

Background: Health-related quality of life, as evaluated by a patient-reported outcomes measure (PROM), is an important prognostic marker in patients with chronic heart failure. This study aimed to use PROM to establish an effective readmission nomogram for chronic heart failure.

Methods: Using a PROM as a measurement tool, we conducted a readmission nomogram for chronic heart failure on a prospective observational study comprising of 454 patients with chronic heart failure hospitalized between May 2017 to January 2020. A Concordance index and calibration curve were used to evaluate the discriminative ability and predictive accuracy of the nomogram. A bootstrap resampling method was used for internal validation of results.

Results: The median follow-up period in the study was 372 days. After a final COX regression analysis, the gender, income, health care, appetite-sleep, anxiety, depression, paranoia, support, and independence were identified and included in the nomogram. The nomogram showed moderate discrimination, with a concordance index of 0.737 (95% CI 0.673-0.800). The calibration curves for the probability of readmission for patients with chronic heart failure showed high consistency between the probability, as predicted, and the actual probability.

Conclusions: This model offers a platform to assess the risk of readmission for different populations with CHF and can assist clinicians with personalized treatment recommendations.
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http://dx.doi.org/10.1186/s12955-020-01534-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7450976PMC
August 2020

Corrigendum to "A novel long non-coding RNA LINC00355 promotes proliferation of lung adenocarcinoma cells by down-regulating miR-195 and up-regulating the expression of CCNE1" [Cell Signal. 2020 Feb;66:109462. doi: 10.1016/j.cellsig.2019.109462].

Cell Signal 2020 Sep 21;73:109715. Epub 2020 Jul 21.

Department of Pathology, College of Basic Medical Science and First Affiliated Hospital, China Medical University, Shenyang 110122, PR China.

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http://dx.doi.org/10.1016/j.cellsig.2020.109715DOI Listing
September 2020

Fabrication and Performance of Self-Supported Flexible Cellulose Nanofibrils/Reduced Graphene Oxide Supercapacitor Electrode Materials.

Molecules 2020 Jun 17;25(12). Epub 2020 Jun 17.

College of Materials Science and Engineering, Nanjing Forestry University, Nanjing 210037, China.

With the rapid development of portable and wearable electronic devices, self-supporting flexible supercapacitors have attracted much attention, and higher requirements have been put forward for the electrode of the device, that is, it is necessary to have good mechanical properties while satisfying excellent electrochemical performance. In this work, a facile method was invented to obtain excellent self-supported flexible electrode materials with high mechanical properties and outstanding electrochemical performance by combining cellulose nanofibrils (CNFs) and reduced graphene oxide (RGO). We focused on the effect of the ratio of the addition of CNFs and the formation process of the film on the electrochemical and mechanical properties. The results show that the CNFs/RGO (where the ratio of CNFs to GO is 1:2) film displayed outstanding comprehensive properties; its tensile strength and conductivity were up to 83 MPa and 202.94 S/m, respectively, and its C value was as high as 146 mF cm under the current density of 5 mA cm. Furthermore, the initial retention rate of the specific capacitance was about 83.7% when recycled 2000 times; moreover, its capacitance did not change much after perpendicular bending 200 times. Therefore, the films prepared by this study have great potential in the field of flexible supercapacitors.
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http://dx.doi.org/10.3390/molecules25122793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356253PMC
June 2020

Tracing Sweetgum Lignin's Molecular Properties through Biorefinery Processing.

ChemSusChem 2020 Sep 22;13(17):4613-4623. Epub 2020 Jun 22.

Department of Forest Biomaterials, North Carolina State University, Campus Box 8005, Raleigh, NC, 27695, USA.

Changes to the molecular properties of lignin over the course of biorefinery processing were investigated by using sweetgum as a feedstock. Hydrothermal pretreatment has been used because it is an economically attractive, green process. Three representative biorefinery lignin preparations were obtained, with about 70 % yield based on raw lignin. The three fractions included soluble lignin adsorbed on resin (XADL), solvent-extracted lignin (HTCELp), and an additional ball-milled residual lignin (HTRELp). By comparing the raw and biorefinery lignin preparations, it can be concluded that lignin undergoes both degradation and condensation throughout the various stages of the hydrothermal-based biorefinery process. The two fractions made soluble by biorefinery processing, XADL and HTCELp, were found to be low-molecular-weight degradation products enriched with free phenolic hydroxyl groups. In addition, about 15 % of noncondensed phenolic units were involved in condensation reactions. Quantitative NMR spectroscopy analysis revealed that at least about 28 % of β-O-4' substructures were cleaved. Hibbert's ketones were identified in XADL and HTRELp, which provided evidence of lignin undergoing acidolysis. The contents of β-5' and β-β' did not change significantly upon biorefinery processing. Finally, episyringaresinol was detected in XADL and HTCELp. It is hoped that these findings will help to further demonstrate the specific effects of biorefinery processing on lignin in hardwood and facilitate its utilization to improve biorefinery economics.
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http://dx.doi.org/10.1002/cssc.202001125DOI Listing
September 2020

Lamin B2 promotes the malignant phenotype of non-small cell lung cancer cells by upregulating dimethylation of histone 3 lysine 9.

Exp Cell Res 2020 08 13;393(2):112090. Epub 2020 May 13.

Department of Pathology, College of Basic Medical Sciences, China Medical University, China; The First Affiliated Hospital of China Medical University, China. Electronic address:

The relationship between Lamin B2 and tumor proliferation and migration is unclear. We explored the impact of Lamin B2 on non-small cell lung cancer (NSCLC) cells. Tissue microarray and immunohistochemistry were combined to evaluate Lamin B2 expression and its relationship with the clinicopathological factors found in NSCLC. Western blotting, immunofluorescence analysis, and bioinformatics were used to investigate the effects of Lamin B2 on various regulatory pathways in cancer. Cytological experiments were conducted to evaluate Lamin B2 expression in tumor cells. We conducted co-immunoprecipitation and chromatin immunoprecipitation to explore the molecular mechanisms underlying the relationship between Lamin B2 and NSCLC and evaluate the results of rescue experiments. Lamin B2 was highly expressed in NSCLC and positively correlated with lymph node metastasis. In NSCLC, Lamin B2 interacted with Cyclin D1, upregulating G9α expression, thus increasing H3K9me2 levels. H3K9me2 binds to the promoter region of the E-cadherin gene (CDH1) to induce CDH1 silencing and promotes cancer cell migration. Thus, we found that Lamin B2 was highly expressed in NSCLC cells and promoted their migration by increasing H3K9me2 levels, which induced E-cadherin gene silencing.
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http://dx.doi.org/10.1016/j.yexcr.2020.112090DOI Listing
August 2020

ANKHD1 promotes proliferation and invasion of non‑small‑cell lung cancer cells via regulating YAP oncoprotein expression and inactivating the Hippo pathway.

Int J Oncol 2020 May 19;56(5):1175-1185. Epub 2020 Feb 19.

Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning 110001, P.R. China.

The ankyrin repeat and KH domain‑containing 1 (ANKHD1) protein was recently reported to be a potential member of the Hippo signaling pathway. However, its role in human non‑small‑cell lung cancer (NSCLC) has not been extensively investigated. The aim of the present study was to examine the expression of ANKHD1 in primary human tissues and cells and determine whether it is correlated with the clinical characteristics of tumor growth. The biological functions of ANKHD1 were evaluated in vitro and in vivo. Yes‑associated protein (YAP) expression and phosphorylation induced by ANKHD1 were evaluated by western blotting and immunoprecipitation. Marked upregulation of ANKHD1 protein expression was observed in NSCLC cells and tissues, which was associated with advanced pathological tumor‑node‑metastasis stage, lymph node metastasis and poor prognosis in patients with NSCLC. ANKHD1 overexpression also promoted the proliferation and invasion of NSCLC cells. ANKHD1 upregulation inactivated Hippo signaling via increasing YAP protein levels, as well as inhibiting YAP protein phosphorylation, whereas depletion of YAP abolished the effects of ANKHD1 on cell proliferation and invasion. Therefore, ANKHD1 may play an important role in NSCLC through regulating the YAP‑dependent Hippo signaling pathway.
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http://dx.doi.org/10.3892/ijo.2020.4994DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7115354PMC
May 2020

A Rail Fastener Tightness Detection Approach Using Multi-source Visual Sensor.

Sensors (Basel) 2020 Mar 2;20(5). Epub 2020 Mar 2.

School of Science, Beijing Jiaotong University; Beijing 100044, China.

At present, the method of two-dimensional image recognition is mainly used to detect the abnormal fastener in the rail-track inspection system. However, the too-tight-or-too-loose fastener condition may cause the clip of the fastener to break or loose due to the high frequency vibration shock, which is difficult to detect from the two-dimensional image. In this practical application background, 3D visual detection technology provides a feasible solution. In this paper, we propose a fundamental multi-source visual data detection method, as well as an accurate and robust fastener location and nut or bolt segmentation algorithm. By combining two-dimensional intensity information and three-dimensional depth information generated by the projection of line structural light, the locating of nut or bolt position and accurate perception of height information can be realized in the dynamic running environment of railway. The experimental results show that the static measurement accuracy in the vertical direction using the structural light vision sensor is 0.1 mm under the laboratory condition, and the dynamic measurement accuracy is 0.5 mm under the dynamic train running environment. We use dynamic template matching algorithm to locate fasteners from 2D intensity map, which achieves 99.4% accuracy, then use the watershed algorithm to segment the nut and bolt from the corresponding depth image of located fastener. Finally, the 3D shape of the nut and bolt is analyzed to determine whether the nut or bolt height meets the local statistical threshold requirements, so as to detect the hidden danger of railway transportation caused by too loose or too tight fasteners.
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http://dx.doi.org/10.3390/s20051367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7085639PMC
March 2020

Thermal conductivity of defective graphene: an efficient molecular dynamics study based on graphics processing units.

Authors:
Xin Wu Qiang Han

Nanotechnology 2020 May 7;31(21):215708. Epub 2020 Feb 7.

Department of Engineering Mechanics, School of Civil Engineering and Transportation, South China University of Technology, Guangzhou, Guangdong Province 510640, People's Republic of China.

The exceptional thermal transport properties of graphene are affected due to the presence of various topological defects, which include single vacancy, double vacancies and Stone-Wales defects. The present article is intended to study on thermal transport properties of defective graphene by comparing the effects of topological defects on the thermal conductivity of graphene. This study developed a program for constructing defective graphene models with customizable defect concentrations and distribution types. The efficient molecular dynamics method based on graphics processing units is applied, which can achieve efficient and accurate calculation of material thermal conductivity. It is revealed that the existence of topological defects has a considerable reduce on the thermal conductivity of graphene, and the declining rate of the value get less with increasing defects concentration. At the same concentration, the weakening effect of SW defects on the thermal conductivity of graphene is evidently less than the other two defects. We also explored the effect of temperature on the thermal conductivity of graphene with different defects. These findings were discussed from the phonon perspective that elucidate the atomic level mechanisms, which provide guidance for thermal management of graphene devices.
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http://dx.doi.org/10.1088/1361-6528/ab73bcDOI Listing
May 2020

Effectiveness and Safety Evaluation of Qixiong Zhongzi Decoction () in Idiopathic Asthenozoospermia Treatment: A Randomized Controlled Trial.

Chin J Integr Med 2020 Feb 29;26(2):146-151. Epub 2020 Jan 29.

Graduate School, China Academy of Chinese Medical Sciences, Beijing, 100700, China.

Objective: To evaluate the clinical effectiveness and safety of the Chinese medicine (CM) Qixiong Zhongzi Decoction (, QZD) in the treatment of patients with idiopathic asthenozoospermia.

Methods: A total number of 66 patients with idiopathic asthenozoospermia were included and randomly divided into treatment and control groups by SAS-generated code from January 2015 to August 2016, 33 patients in each group. Patients in the treatment group were administered with 150 mL of QZD twice a day, whereas those in the control group were given 1 g of levocarnitine oral liquid twice a day. The two groups received the indicated medication for 12 weeks and were then followed up for 4 weeks. The primary outcome was sperm motility, and the secondary therapeutic indices were sperm volume, density, pregnancy probability, and CM syndrome score. The comparison between groups was carried out at 4, 8 and 12 weeks, respectively. The safety was determined before and after treatment.

Results: (1) Drop-off: 5 cases (7.58%) were lost after treatment (2 from the treatment group and 3 from the control group). (2) Primary outcomes: after 8- and 12-week treatment, the progressive sperms in the two groups were significantly higher than the baseline (all P<0.05); however, the treatment group showed greater improvement compared with the control group at 12-week treatment (22.7% ± 9.0% vs. 14.1% ±8.8%, P<0.05). The increasement of non-progressive grade sperms at both groups was observed at 8- and 12-week treatment with statistical difference (all P<0.05), however, the treatment group showed remarkable improvement compared with the control group at 12-week treatment (38.7% ±14.1% vs. 26.2% ±15.4%, P<0.05). (3) Secondary outcomes: no significant statistical differences were found in semen volume and density (4, 8, and 12-week treatment) and pregnancy probability of patients' wives (12-week treatment) between two groups (all P>0.05), however, the CM syndrome score of the treatment group significantly declined compared with baseline level at each time points (all P<0.05). (4) Safety: no obvious side reactions were found during the treatment in both groups.

Conclusion: QZD could improve the progressive and non-progressive grade sperm in the treatment of idiopathic asthenozoospermia. It is safe with no obvious side effects.
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http://dx.doi.org/10.1007/s11655-020-3211-7DOI Listing
February 2020

Use of intraoperative ultrasonography for identification and management of pneumothorax caused by iatrogenic diaphragm defect: a case report and literature review.

J Int Med Res 2020 Jan;48(1):300060519898048

Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.

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http://dx.doi.org/10.1177/0300060519898048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113711PMC
January 2020

Correction to: ZNF326 promotes malignant phenotype of glioma by up-regulating HDAC7 expression and activating Wnt pathway.

J Exp Clin Cancer Res 2020 Jan 16;39(1):14. Epub 2020 Jan 16.

Department of Pathology, College of Basic Medical Sciences, and First Affiliated Hospital of China Medical University, Shenyang, China.

In the original publication of this manuscript [1], the author mislabeled the CTL group and ZNF326 group in Fig. 2-I,J (MTT result). The revised Fig. 2 is shown below.
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http://dx.doi.org/10.1186/s13046-020-1526-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6964022PMC
January 2020

Transcription Factor ZNF326 Upregulates the Expression of ERCC1 and HDAC7 and its Clinicopathologic Significance in Glioma.

Lab Med 2020 Jul;51(4):377-384

Department of Surgical Oncology and Breast Surgery, First Affiliated Hospital of China Medical University, Shenyang, China.

Previous reports that we have coauthored have shown that transcription factor ZNF326 can upregulate the expression of ERCC1 and HDAC7, and downregulate the expression of LTBP4 and ZNF383 in lung-cancer cells. However, whether tissue-specificity of the ZNF326 function exists in glioma tissue remains unclear. In this study, overexpression or knockdown of ZNF326 in glioma cells caused upregulation or downregulation, respectively, of the protein and micro RNA (mRNA) levels of ERCC1 and HDAC7. The levels of LTBP4 and ZNF383 were not significantly changed. Immunohistochemical results showed that ZNF326 was not only highly expressed in glioma but was also positively correlated with the expression of ERCC1 and HDAC7. Moreover, the expression of ERCC1 and HDAC7 was enhanced with the increase in tumor grade. However, there was no correlation between ZNF326 and the expression of LTBP4 and ZNF383. Therefore, the detection of ZNF326, ERCC1, and HDAC7 expressions was useful for identifying different grades of glioma.
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http://dx.doi.org/10.1093/labmed/lmz075DOI Listing
July 2020

TEX19 promotes ovarian carcinoma progression and is a potential target for epitope vaccine immunotherapy.

Life Sci 2020 Jan 13;241:117171. Epub 2019 Dec 13.

Department of Pharmacology, School of Pharmacy, China Medical University, No.77, Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, PR China; Liaoning Key Laboratory of molecular targeted anti-tumor drug development and evaluation, China Medical University, No.77, Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, PR China; Liaoning Cancer immune peptide drug Engineering Technology Research Center, China Medical University, No.77, Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, PR China; Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, No.77, Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, PR China. Electronic address:

Aims: Testis Expressed 19 (TEX19) is one of cancer/testis antigens identified in recent years and is related to the oncogenesis and progress of several cancers. This study aimed to reveal the role of TEX19 in ovarian cancer (OC) and searched for potential candidate epitope peptides of TEX19 to facilitate clinical application.

Main Methods: TEX19 levels were evaluated by immunohistochemistry (IHC) in 98 human ovarian tissue samples. The correlation of TEX19 levels with patients' clinicopathological features was assessed. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting analysis were utilized to detect TEX19 levels in ovarian cell lines and TEX19-deficient cells. The level of TEX19 in OVCAR-3 and A2780 was knocked down by small interfering RNA (siRNA), and loss-of-function assays were used to determine the biological effects of TEX19 on the proliferation, migration, and invasion of OC cells. Subsequently, candidate epitope peptides from TEX19 were predicted and verified by the IEDB database, pepsite2 website, MOE software, and T2 cell binding assay.

Key Findings: TEX19 was significantly upregulated in OC which correlated to higher TNM stage, lymph node involvement, and invasiveness. Knockdown of TEX19 inhibited proliferation, migration, and invasion of OC cells. Additionally, we screened four peptides derived from TEX19 and found TL to be the dominant peptide with the greatest affinity with HLA-A*0201.

Significance: Our data indicated a cancer-promoting effect of TEX19 in OC and demonstrated that TL could be a potential candidate for an anti-tumor epitope vaccine of OC, suggesting that TEX19 is a promising biomarker and immunotherapeutic target for OC.
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http://dx.doi.org/10.1016/j.lfs.2019.117171DOI Listing
January 2020

Analysis Of Re-Hospitalizations For Patients With Heart Failure Caused By Coronary Heart Disease: Data Of First Event And Recurrent Event.

Ther Clin Risk Manag 2019 14;15:1333-1341. Epub 2019 Nov 14.

Department of Cardiology, The 1st Hospital of Shanxi Medical University, Taiyuan, Shanxi Province 030001, People's Republic of China.

Background: The re-hospitalization rate of patients with heart failure remains at a high level, and studies of the subject have focused mainly on event-time outcomes. In addition to using re-hospitalization data with the outcomes of the event-time-count, this study introduces the conditional frailty model, which could help obtain more reasonable results.

Materials And Methods: This prospective observational cohort study enrolled 1484 patients with heart failure caused by coronary heart disease. The outcomes of heart failure readmissions and the case report form data were collected. Based on the traditional Cox model with event-time outcomes, the mixed effects of a conditional frailty model were added to analyze the event-time-count longitudinal data.

Results: The Cox regression model showed that non-manual work, diastolic dysfunction, and better medical compensation increased the risk of heart failure readmission, whereas treatment with beta-blockers decreased the risk. The conditional frailty model further revealed that age, female sex, non-manual work, better medical compensation, longer QRS duration, and treatment with percutaneous coronary intervention increased the risk of heart failure readmission.

Conclusion: This study obtained more reliable, reasonable results based on longitudinal data and a mixed model. The results could provide more clinical epidemiological evidence for the management of heart failure.
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http://dx.doi.org/10.2147/TCRM.S218694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6861516PMC
November 2019

Epigenetics Regulates Reproductive Development in Plants.

Plants (Basel) 2019 Dec 2;8(12). Epub 2019 Dec 2.

Department of Biology, Saint Louis University, St. Louis, MO 63103, USA.

Seed, resulting from reproductive development, is the main nutrient source for human beings, and reproduction has been intensively studied through genetic, molecular, and epigenetic approaches. However, how different epigenetic pathways crosstalk and integrate to regulate seed development remains unknown. Here, we review the recent progress of epigenetic changes that affect chromatin structure, such as DNA methylation, polycomb group proteins, histone modifications, and small RNA pathways in regulating plant reproduction. In gametogenesis of flowering plants, epigenetics is dynamic between the companion cell and gametes. Cytosine DNA methylation occurs in CG, CHG, CHH contexts (H = A, C, or T) of genes and transposable elements, and undergoes dynamic changes during reproduction. Cytosine methylation in the CHH context increases significantly during embryogenesis, reaches the highest levels in mature embryos, and decreases as the seed germinates. Polycomb group proteins are important transcriptional regulators during seed development. Histone modifications and small RNA pathways add another layer of complexity in regulating seed development. In summary, multiple epigenetic pathways are pivotal in regulating seed development. It remains to be elucidated how these epigenetic pathways interplay to affect dynamic chromatin structure and control reproduction.
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http://dx.doi.org/10.3390/plants8120564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6963493PMC
December 2019