Publications by authors named "Zhiyu Wang"

290 Publications

The integrity of the white matter in first-episode schizophrenia patients with auditory verbal hallucinations: An atlas-based DTI analysis.

Psychiatry Res Neuroimaging 2021 Jul 4;315:111328. Epub 2021 Jul 4.

National Clinical Research Center for Mental Disorders, and Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, China; Hunan Key Laboratory of Psychiatry and Mental Health, National Technology Institute of Psychiatry, Changsha, China; Institute of Mental Health, Second Xiangya Hospital, Central South University, Changsha, China. Electronic address:

Auditory verbal hallucination (AVH) is one of the most remarkable symptoms of schizophrenia, with great impact on patients' lives and unclear pathogenesis. Neuroimaging studies have indicated that the development of AVHs is associated with white matter alteration, however, there are still inconsistencies in specific findings across previous investigations. The present study aimed to investigate the characteristics of the microstructural integrity of white matter (WM) in first-episode schizophrenia patients who experience auditory hallucinations. Atlas-based Diffusion Tensor Imaging (DTI) analysis was performed to evaluate the white matter integrity in 37 first-episode schizophrenia patients with AVH, 60 schizophrenia patients without AVH, and 50 healthy controls. Compared with the healthy controls group, AVH showed decreased mean fractional anisotropy (FA) in the genu and body of corpus callosum, right posterior corona radiata, left superior corona radiata, left external capsule, right superior fronto-occipital fasciculus, and higher mean diffusivity (MD) in genu of corpus callosum and left fornix and stria terminalis; whereas the nAVH group showed a much more significant reduction of FA and increased MD in broader brain regions. In addition, a significant positive correlation between FA and the severity of AVHs was observed in right posterior corona radiate. These observations collectively demonstrated that a certain degree of preserved fronto-temporal and interhemispheric connectivity in the early stage of schizophrenia might be associated with the brain capability to generate AVHs.
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http://dx.doi.org/10.1016/j.pscychresns.2021.111328DOI Listing
July 2021

[Treatment of Stage Ia Non-small Cell Lung Cancer in Patients: Comparison of Ablation and Sub-lobectomy].

Zhongguo Fei Ai Za Zhi 2021 Jul 14. Epub 2021 Jul 14.

The First AffilIated Hospital of Xi 'an Jiaotong University, Xi'an 710061, China.

Background: Lung cancer has the highest mortality in China. Different treatments are of great significance to the prognosis of patients. By comparing stage Ia non-small cell lung cancer (NSCLC) patients' survival rates for ablation and for sub-lobectomy, we studied the difference in the effects of the two treatments on patient prognosis.

Methods: Using the Surveillance, Epidemiology, and End Results (SEER) database, we screened eligible patients with stage Ia NSCLC from January 2004 to December 2015. Then, 228 patients treated with ablation and 228 patients treated with sub-lobotomy were then selected based on propensity score matching. After stratification, matching, and adjustment the Kaplan-Meier analysis was performed to compare the overall survival rates of patients treated with the two procedures.

Results: The Kaplan-Meier survival analysis showed that there is a significant difference between the ablation group and the sub-lobectomy group (P<0.05). In the univarlable analysis, the hazard ratio (HR) of sub-lobotomy group was 0.571 (95%CI: 0.455-0.717) compared with the ablation group. Patients treated with sub-lobectomy had a 0.571 times greater risk of adverse outcomes than those treated with ablation. In the multivariable analysis, the HR for sub-lobectomy group was 0.605 (95%CI: 0.477-0.766) compared with the ablation group. Patients treated with sub-lobectomy had a 0.605 time greater risk of adverse outcomes than those treated with ablation. The results suggested that the overall survival rate of patients with stage Ia NSCLC treated with sub-lobotomy was higher than that of patients treated with ablation.

Conclusions: This study suggests that there is a significant difference in overall survival of stage Ia NSCLC patients treated with ablation and with sub-lobotomy. Patients treated with sub-lobotomy for stage Ia NSCLC had higher overall survival than those treated with ablation.
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http://dx.doi.org/10.3779/j.issn.1009-3419.2021.104.09DOI Listing
July 2021

Aiduqing formula suppresses breast cancer metastasis via inhibiting CXCL1-mediated autophagy.

Phytomedicine 2021 Jun 17;90:153628. Epub 2021 Jun 17.

The Research Center of Integrative Cancer Medicine, Discipline of Integrated Chinese and Western Medicine, the Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China; State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Chinese Medicine, Chengdu, Sichuan, China; The Research Center for Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China; Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangdong Provincial Academy of Chinese Medical Sciences, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong, China; Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China. Electronic address:

Background: Metastasis is the most common lethal cause of breast cancer-related death. Recent studies have implied that autophagy is closely implicated in cancer metastasis. Therefore, it is of great significance to explore autophagy-related molecular targets involved in breast cancer metastasis and to develop therapeutic drugs.

Purpose: This study was designed to investigate the anti-metastatic effects and autophagy regulatory mechanisms of Aiduqing (ADQ) formula on breast cancer.

Study Design/methods: Multiple cellular and molecular experiments were conducted to investigate the inhibitory effects of ADQ formula on autophagy and metastasis of breast cancer cells in vitro. Meanwhile, autophagic activator/inhibitor as well as CXCL1 overexpression or interference plasmids were used to investigate the underlying mechanisms of ADQ formula in modulating autophagy-mediated metastasis. Furthermore, the zebrafish xenotransplantation model and mouse xenografts were applied to validate the inhibitory effect of ADQ formula on autophagy-mediated metastasis in breast cancer in vivo.

Results: ADQ formula significantly inhibited the proliferation, migration, invasion and autophagy but induced apoptosis of high-metastatic breast cancer cells in vitro. Similar results were also observed in starvation-induced breast cancer cells which exhibited elevated metastatic ability and autophagy activity. Mechanism investigations further approved that either CXCL1 overexpression or autophagic activator rapamycin can significantly abrogated the anti-metastatic effects of ADQ formula, suggesting that CXCL1-mediated autophagy may be the crucial pathway of ADQ formula in suppressing breast cancer metastasis. More importantly, ADQ formula suppressed breast cancer growth, autophagy, and metastasis in both the zebrafish xenotransplantation model and the mouse xenografts.

Conclusion: Our study not only revealed the novel function of CXCL1 in mediating autophagy-mediated metastasis but also suggested ADQ formula as a candidate drug for the treatment of metastatic breast cancer.
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http://dx.doi.org/10.1016/j.phymed.2021.153628DOI Listing
June 2021

Energy-saving hydrogen production by chlorine-free hybrid seawater splitting coupling hydrazine degradation.

Nat Commun 2021 Jul 7;12(1):4182. Epub 2021 Jul 7.

State Key Lab of Fine Chemicals, Liaoning Key Lab for Energy Materials and Chemical Engineering, PSU-DUT Joint Center for Energy Research, Dalian University of Technology, Dalian, China.

Seawater electrolysis represents a potential solution to grid-scale production of carbon-neutral hydrogen energy without reliance on freshwater. However, it is challenged by high energy costs and detrimental chlorine chemistry in complex chemical environments. Here we demonstrate chlorine-free hydrogen production by hybrid seawater splitting coupling hydrazine degradation. It yields hydrogen at a rate of 9.2 mol h g on NiCo/MXene-based electrodes with a low electricity expense of 2.75 kWh per m H at 500 mA cm and 48% lower energy equivalent input relative to commercial alkaline water electrolysis. Chlorine electrochemistry is avoided by low cell voltages without anode protection regardless Cl crossover. This electrolyzer meanwhile enables fast hydrazine degradation to ~3 ppb residual. Self-powered hybrid seawater electrolysis is realized by integrating low-voltage direct hydrazine fuel cells or solar cells. These findings enable further opportunities for efficient conversion of ocean resources to hydrogen fuel while removing harmful pollutants.
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http://dx.doi.org/10.1038/s41467-021-24529-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263752PMC
July 2021

Autophagy Blockade by Ai Du Qing Formula Promotes Chemosensitivity of Breast Cancer Stem Cells Via GRP78/β-Catenin/ABCG2 Axis.

Front Pharmacol 2021 3;12:659297. Epub 2021 Jun 3.

The Research Center for Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China.

Accumulating evidence suggests that the root of drug chemoresistance in breast cancer is tightly associated with subpopulations of cancer stem cells (CSCs), whose activation is largely dependent on taxol-promoting autophagy. Our pilot study identified GRP78 as a specific marker for chemoresistance potential of breast CSCs by regulating Wnt/β-catenin signaling. Ai Du Qing (ADQ) is a traditional Chinese medicine formula that has been utilized in the treatment cancer, particularly during the consolidation phase. In the present study, we investigated the regulatory effects and molecular mechanisms of ADQ in promoting autophagy-related breast cancer chemosensitivity. ADQ with taxol decreasing the cell proliferation and colony formation of breast cancer cells, which was accompanied by suppressed breast CSC ratio, limited self-renewal capability, as well as attenuated multi-differentiation. Furthermore, autophagy in ADQ-treated breast CSCs was blocked by taxol regulation of β-catenin/ABCG2 signaling. We also validated that autophagy suppression and chemosensitizing activity of this formula was GRP78-dependent. In addition, GRP78 overexpression promoted autophagy-inducing chemoresistance in breast cancer cells by stabilizing β-catenin, while ADQ treatment downregulated GRP78, activated the Akt/GSK3β-mediated proteasome degradation of β-catenin ubiquitination activation, and consequently attenuated the chemoresistance-promoted effect of GRP78. In addition, both mouse breast cancer xenograft and zebrafish xenotransplantation models demonstrated that ADQ inhibited mammary tumor growth, and the breast CSC subpopulation showed obscure adverse effects. Collectively, this study not only reveals the chemosensitizating mechanism of ADQ in breast CSCs, but also highlights the importance of GRP78 in mediating autophagy-promoting drug resistance β-catenin/ABCG2 signaling.
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http://dx.doi.org/10.3389/fphar.2021.659297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210424PMC
June 2021

Roles of conserved residues in the receptor binding sites of human parainfluenza virus type 3 HN protein.

Microb Pathog 2021 Jun 17;158:105053. Epub 2021 Jun 17.

Department of Virology, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China. Electronic address:

Human parainfluenza virus type 3 (hPIV-3) entry and intrahost spread through membrane fusion are initiated by two envelope glycoproteins, hemagglutinin-neuraminidase (HN) and fusion (F) protein. Binding of HN protein to the cellular receptor via its receptor-binding sites triggers conformational changes in the F protein leading to virus-cell fusion. However, little is known about the roles of individual amino acids that comprise the receptor-binding sites in the fusion process. Here, residues R192, D216, E409, R424, R502, Y530 and E549 located within the receptor-binding site Ⅰ, and residues N551 and H552 at the putative site Ⅱ were replaced by alanine with site-directed mutagenesis. All mutants except N551A displayed statistically lower hemadsorption activities ranging from 16.4% to 80.2% of the wild-type (wt) level. With standardization of the number of bound erythrocytes, similarly, other than N551A, all mutants showed reduced fusogenic activity at three successive stages: lipid mixing (hemifusion), content mixing (full fusion) and syncytium development. Kinetic measurements of the hemifusion process showed that the initial hemifusion extent for R192A, D216A, E409A, R424A, R502A, Y530A, E549A and H552A was decreased to 69.9%, 80.6%, 71.3%, 67.3%, 50.6%, 87.4%, 84.9% and 25.1%, respectively, relative to the wt, while the initial rate of hemifusion for the E409A, R424A, R502A and H552A mutants was reduced to 69.0%, 35.4%, 62.3%, 37.0%, respectively. In addition, four mutants with reduced initial hemifusion rates also showed decreased percentages of F protein cleavage from 43.4% to 56.3% of the wt. Taken together, Mutants R192A, D216A, E409A, R424A, R502A, Y530A, E549A and H552A may lead to damage on the fusion activity at initial stage of hemifusion, of which decreased extent and rate may be associated with impaired receptor binding activity resulting in the increased activation barrier of F protein and the cleavage of it, respectively.
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http://dx.doi.org/10.1016/j.micpath.2021.105053DOI Listing
June 2021

Design, synthesis, and biological evaluation of furosemide analogs as therapeutics for the proteopathy and immunopathy of Alzheimer's disease.

Eur J Med Chem 2021 Jun 2;222:113565. Epub 2021 Jun 2.

Krembil Research Institute, University Health Network, Toronto, Canada; Faculty of Pharmacy, University of Toronto, Ontario, Canada; Faculty of Medicine, University of Toronto, Ontario, Canada; Department of Chemistry, University of Toronto, Ontario, Canada. Electronic address:

β-Amyloid (Aβ) triggered proteopathic and immunopathic processes are a postulated cause of Alzheimer's disease (AD). Monomeric Aβ is derived from amyloid precursor protein, whereupon it aggregates into various assemblies, including oligomers and fibrils, which disrupt neuronal membrane integrity and induce cellular damage. Aβ is directly neurotoxic/synaptotoxic, but may also induce neuroinflammation through the concomitant activation of microglia. Previously, we have shown that furosemide is a known anthranilate-based drug with the capacity to downregulate the proinflammatory microglial M1 phenotype and upregulate the anti-inflammatory M2 phenotype. To further explore the pharmacologic effects of furosemide, this study reports a series of furosemide analogs that target both Aβ aggregation and neuroinflammation, thereby addressing the combined proteopathic-immunopathic pathogenesis of AD. Forty compounds were synthesized and evaluated. Compounds 3c, 3g, and 20 inhibited Aβ oligomerization; 33 and 34 inhibited Aβ fibrillization. 3g and 34 inhibited the production of TNF-α, IL-6, and nitric oxide, downregulated the expression of COX-2 and iNOS, and promoted microglial phagocytotic activity, suggesting dual activity against Aβ aggregation and neuroinflammation. Our data demonstrate the potential therapeutic utility of the furosemide-like anthranilate platform in the development of drug-like molecules targeting both the proteopathy and immunopathy of AD.
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http://dx.doi.org/10.1016/j.ejmech.2021.113565DOI Listing
June 2021

Causal augmented ConvNet: A temporal memory dilated convolution model for long-sequence time series prediction.

ISA Trans 2021 May 19. Epub 2021 May 19.

State Key Laboratory of Industrial Control Technology, College of Control Science and Engineering, Zhejiang University, Hangzhou 310027, PR China. Electronic address:

A number of deep learning models have been proposed to capture the inherent information in multivariate time series signals. However, most of the existing models are suboptimal, especially for long-sequence time series prediction tasks. This work presents a causal augmented convolution network (CaConvNet) and its application for long-sequence time series prediction. First, the model utilizes dilated convolution with enlarged receptive fields to enhance global feature extraction in time series. Secondly, to effectively capture the long-term dependency and to further extract multiscale features that represent different operating conditions, the model is augmented with a long-short term memory network. Thirdly, the CaConvNet is further optimized with a dynamic hyperparameter search algorithm to reduce uncertainties and the cost of manual hyperparameter selection. Finally, the model is extensively evaluated on a predictive maintenance task using the turbofan aircraft engine run-to-failure prognostic benchmark dataset (C-MAPSS). The performance of the proposed CaConvNet is also compared with four conventional deep learning models and seven different state-of-the-art predictive models. The evaluation metrics show that the proposed CaConvNet outperforms other models in most of the prognostic tasks. Moreover, a comprehensive ablation study is performed to provide insights into the contribution of each sub-structure of the CaConvNet model to the observed performance. The results of the ablation study as well as the performance improvement of CaConvNet are discussed in this paper.
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http://dx.doi.org/10.1016/j.isatra.2021.05.026DOI Listing
May 2021

A network meta-analysis on the effectiveness and safety of acupuncture in treating patients with major depressive disorder.

Sci Rep 2021 May 17;11(1):10384. Epub 2021 May 17.

Hong Kong Chinese Medicine Clinical Study Center, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, 999077, Hong Kong SAR, China.

Acupuncture is an important alternative therapy in treating major depressive disorder (MDD), but its efficacy and safety are still not well assessed. This study is the first network meta-analysis exploring the effectiveness and safety of acupuncture, common pharmacological treatments or other non-medication therapies for MDD. Eight databases including PubMed, Embase, Allied and Complementary Medicine Database, Cochrane Library, Wan Fang Data, China National Knowledge Infrastructure, China Biology Medicine disc, and Chongqing VIP Database were searched up to Jan 17, 2021. Articles were screened and selected by two reviewers independently. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the certainty of the evidence. A total of 71 eligible studies were included. The network analysis results indicated that the combined interventions of electro-acupuncture (EA) with selective serotonin reuptake inhibitors (SSRIs) and manual acupuncture (MA) with SSRIs were more effective in improving depression symptoms compared with acupuncture alone, pharmacological interventions alone, or other inactive groups. Among all the regimens, EA with SSRIs was found to have the highest effect in improving depression symptoms of MDD. In addition, there were slight differences in the estimations of the various treatment durations. The combination of acupuncture and serotonin-norepinephrine reuptake inhibitors (SNRIs) was found to be more effective than SNRIs alone. In conclusion, acupuncture and its combinations could be safe and effective interventions for MDD patients. EA with SSRIs seems to be the most effective intervention among the assessed interventions. Well-designed and large-scale studies with long-term follow-up should be conducted in the future.
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http://dx.doi.org/10.1038/s41598-021-88263-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129113PMC
May 2021

Immune checkpoint inhibitors for treatment of small-cell lung cancer: a systematic review and meta-analysis.

Ann Transl Med 2021 Apr;9(8):705

The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.

Background: Small cell lung cancer (SCLC) is a very aggressive and proliferative disease, with little progress being having made for its treatment in decades. Our goal was to evaluate the effect of immune checkpoint inhibitors (ICIs) and identify optimal first-line interventions for the treatment of SCLC.

Methods: A systematic literature search of the Cochrane Library, PubMed and oncology conference proceedings were conducted. Randomized trials evaluating ICIs for SCLC were included. We use the risk of bias tool in RevMan 5.3 to assess the quality of studies. We used Stata version 15.0 to carry out data direct comparison and R version 4.0.2 to conduct the Bayesian network analysis.

Results: A total of 16 relevant clinical trials comprising 4,476 patients were included. We found the magnitude of efficacy for ICIs as first-line therapy conferred a statistically significant benefit in overall survival (OS) and progression-free survival compared to chemotherapy alone. The results were 0.82 (95% CI, 0.76-0.89, P<0.001) and 0.80 (95% CI, 0.74-0.86, P<0.001). For objective response rate (ORR), the result (1.13, 95% CI, 0.97-1.31, P=0.109) was not significant. In the second-line and maintenance treatment, no additional benefit was observed. With regard to safety, results showed that for all grades of AEs and grades 3-4 AEs, the pooled results were 1.36 (95% CI: 0.50-3.70; P=0.543) and 1.35 (95% CI: 0.58-3.15; P=0.484) respectively. In addition, the indirect comparison results showed that nivolumab combined with chemotherapy led to the most significant improvement in OS, while durvalumab combined with chemotherapy was a more efficacious therapy for improving ORR compared with the other interventions; the probability were the best treatments was 73.93% and 81% respectively.

Discussion: Our results showed ICIs combined with etoposide and platinum-based drugs as first-line treatment of SCLC have benefits for patients and there was no evidence of a significant difference in efficacy among the different ICI drugs used for the first-line therapy. As for toxicity, the ICIs did not increase the frequency AEs for patients. However, as some studies are ongoing and the full data have still not been reported, our conclusions may not be completely representative.
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http://dx.doi.org/10.21037/atm-21-1423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106042PMC
April 2021

TOX Acts as a Tumor Suppressor by Inhibiting mTOR Signaling in Colorectal Cancer.

Front Immunol 2021 9;12:647540. Epub 2021 Apr 9.

Department of Internal Oncology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

The treatment and prognosis of advanced colorectal cancer (CRC) remain a challenging clinical research focus. Here, we describe a new CRC tumor suppressor and potential therapeutic target: thymocyte selection associated high mobility group box (TOX) protein. The expression of TOX was lower in CRC than para-CRC. With the increase of tumor stage, TOX expression decreased, indicating the presence of TOX relates to better overall survival (OS). TOX suppressed the mechanistic target of rapamycin kinase (mTOR) signaling to inhibit cell proliferation, migration, invasion, and change the epithelial-mesenchymal transition (EMT) process. In addition, TOX promoted apoptosis. As tumor mutation burden and tumor microenvironment play vital roles in the occurrence and development of tumors, we analyzed the TOX expression in the immune microenvironment of CRC. The high TOX expression was negatively correlated with TumorPurity. Moreover, it was positively related to ImmuneScore, StromalScore, microsatellite instability (MSI) status, and Consensus Molecular Subtypes (CMS) 3 typing. Based on gene set enrichment analysis (GSEA), the reduced expression of TOX activated mTOR. We found rapamycin, a mTOR inhibitor, partly inhibited cell proliferation, invasion, and migration in shTOX HCT116 cells. Lastly, TOX suppressed tumorigenesis and lung metastasis of CRC . Rapamycin alone or combined with PD1 inhibitor is more effective than PD1 inhibitor alone in a tumor model. Taken together, these findings highlight the tumor-suppressive role of TOX in CRC, especially in MSI CRC, and provide valuable information that rapamycin alone or combined with PD1 inhibitor has therapeutic potential in CRC.
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http://dx.doi.org/10.3389/fimmu.2021.647540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062716PMC
April 2021

The effect of the HRB linker of Newcastle disease virus fusion protein on the fusogenic activity.

J Microbiol 2021 May 29;59(5):513-521. Epub 2021 Mar 29.

Department of Virology, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, 250014, China.

Newcastle disease, designated a class A disease of poultry by the Office international des epizooties (OIE), is an acute infection caused by Newcastle disease virus (NDV). The merging of the envelope of NDV with the membrane of a target host cell is the key step in the infection pathway, which is driven by the concerted action of two glycoproteins: haemagglutinin-neuraminidase (HN) and fusion (F) protein. When the HN protein binds to the host cell surface receptor, the F protein is activated to mediate fusion. The three-dimensional structure of the F protein has been reported to have low electron density between the DIII domain and the HRB domain, and this electron-poor region is defined as the HRB linker. To clarify the contributing role of the HRB linker in the NDV F protein-mediated fusion process, 6 single amino acid mutants were obtained by site-directed mutagenesis of the HRB linker. The expression of the mutants and their abilities to mediate fusion were analysed, and the key amino acids in the HRB linker were identified as L436, E439, I450, and S453, as they can modulate the fusion ability or expression of the active form to a certain extent. The data shed light on the crucial role of the F protein HRB linker in the acquisition of a normal fusogenic phenotype.
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http://dx.doi.org/10.1007/s12275-021-0539-4DOI Listing
May 2021

Morphology/Interstitial Fluid Pressure-Tunable Nanopomegranate Designed by Alteration of Membrane Fluidity under Tumor Enzyme and PEGylation.

Mol Pharm 2021 05 26;18(5):2039-2052. Epub 2021 Mar 26.

School of Pharmacy, China Pharmaceutical University, No. 639, Longmian Road, Nanjing 210009, PR China.

Up to now, insufficient drug accumulation in tumor remains a major challenge for nanochemotherapy. However, the spherical nanocarriers with large diameter, which are beneficial for blood circulation and tumor extravasation, cannot travel deep in a tumor. Additionally, high tumor interstitial fluid pressure (IFP) in the tumor microenvironment may promote the efflux of the penetrable nanodrugs. Therefore, the size and shape of nanocarriers as well as the tumoral IFP can be regulated synchronously for improved tumor penetration and combined chemotherapy. Herein, a novel dual-functional polymer-polypeptide (Biotin-PEG-GKGPRQITITK) for both verified tumor targeting and responsiveness was synthesized to construct the "peel" of nanopomegranate-like nanovectors (DI-MPL), in which docetaxel-loaded micelles was encapsulated as "seeds". Interestingly, DI-MPL was endowed multi-abilities of tunable size/shape switch and controlled release of IFP alleviator imatinib (IM), which were developed with one and the same strategy-alteration of membrane fluidity under the cleavage of polymer-polypeptide and PEGylation. As a result, the peel of DI-MPL could turn into small pieces with the seed scattered out in response to matrix metalloproteinase-9 (MMP-9), making nanopomegranate (180 nm) switch into spheres/disks (40 nm), during which IM is released to reduce IFP synchronously. With prominent tumor penetration ability in both multicellular tumor spheroids (MCTS) and tumor tissue, DI-MPL exhibited optimal inhibition of MCTS growth and the enhanced chemotherapy in comparison to other preparations. Meanwhile, the improved penetrability of DI-MPL in tumor tissue was found to be related to the reduced IFP, which is achieved via inhibiting expression of phosphorylated platelet-derived growth factor receptor-β (-PDGFR-β) by IM. Altogether, the bilateral adjusting strategies from nanocarrier size/shape and tumoral IFP with a single enzyme-responsive material could provide a potential combined chemotherapy to improve tumor penetration.
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http://dx.doi.org/10.1021/acs.molpharmaceut.1c00036DOI Listing
May 2021

The HNF1A-AS1/miR-92a-3p axis affects the radiosensitivity of non-small cell lung cancer by competitively regulating the JNK pathway.

Cell Biol Toxicol 2021 Mar 23. Epub 2021 Mar 23.

Department of Thoracic Surgery, Fourth Hospital of Hebei Medical University, No. 12 Jiankang Road, Shijiazhuang City, Hebei Province, 050011, People's Republic of China.

Background: It has been widely reported that long non-coding RNAs (lncRNAs) could affect the varieties of tumor response to radiotherapy. LncRNA HNF1A-AS1 is transcribed from HNF1A gene cluster's antisense strand. This work focused on the mechanism of how HNF1A-AS1 participated in the radiosensitivity of non-small cell lung cancer (NSCLC).

Methods: The mRNA or protein expression of HNF1A-AS1, miR-92a-3p MAP2K4, and JNK in NSCLC cells and tissues was detected by qRT-PCR or western blotting. RNA immunoprecipitation (RIP) detection and luciferase reporting system were used to evaluate the relationship between HNFA-AS1 and miR-92a-3p or between miR-92a-3p and MAP2K4. Flow cytometry assays, colony formation, and MTT were performed to analyze the function changes in A549 and Calu-1 cells. The rescue experiment was also conducted to explore the underlying mechanisms.

Results: HNF1A-AS1 was investigated in NSCLC cells and tissues and highly related to the advanced pathological stage. HNF1A-AS1 bound with miR-92a-3p, which was downregulated in NSCLC. It showed that miR-92a-3p was negatively related to HNF1A-AS1. Knockdown of HNF1A-AS1 impacted most cell biological behaviors in NSCLC cells, including restricting the proliferation and aggravating apoptosis. Furthermore, knockdown of HNF1A-AS1 dramatically enhanced radiotherapy sensitivity of NSCLC. Moreover, miR-92a-3p was found to target MAP2K4 and could reduce MAP2K4 expression. Inhibition of HNF1A-AS1 elevated radiotherapy sensitivity and retarded the progression of NSCLC cells, followed by decreasing expression levels of MAP2K4. Besides, MAP2K4 mimic rescued the si-HNF1A-AS1 effects on the biological behavior of NSCLC cells.

Conclusion: HNF1A-AS1 is highly expressed in NSCLC. MiR-92a-3p is the target gene of HNF1A-AS1 and involved in tumor progression by regulating the MAP2K4/JNK pathway. HNF1AS1/miR-92a-3p/MAP2K4 axis plays important roles in radiotherapy resistance of NSCLC.
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http://dx.doi.org/10.1007/s10565-021-09595-zDOI Listing
March 2021

Machine Learning Algorithm Guiding Local Treatment Decisions to Reduce Pain for Lung Cancer Patients with Bone Metastases, a Prospective Cohort Study.

Pain Ther 2021 Jun 19;10(1):619-633. Epub 2021 Mar 19.

Department of Internal Oncology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai, People's Republic of China.

Introduction: As life expectancy increases for lung cancer patients with bone metastases, the need for personalized local treatment to reduce pain is expanding.

Methods: Patients were treated by a multidisciplinary team (MDT), and local treatment including surgery, percutaneous osteoplasty, or radiation. Visual analog scale (VAS) and quality of life (QoL) scores were analyzed. VAS at 12 weeks after treatment was the main outcome. We developed and tested machine learning models to predict which patients should receive local treatment. Model discrimination was evaluated by the area under curve (AUC), and the best model was used for prospective decision-making accuracy validation.

Results: Under the direction of MDT, 161 patients in the training set, 32 patients in the test set, and 36 patients in the validation set underwent local treatment. VAS in surgery, percutaneous osteoplasty, and radiation groups decreased significantly to 4.78 ± 1.28, 4.37 ± 1.36, and 5.39 ± 1.31 at 12 weeks, respectively (p < 0.05), with no significant differences among the three datasets, and improved QoL was also observed (p < 0.05). A decision tree (DT) model that included VAS, bone metastases character, Frankel classification, Mirels score, age, driver gene, aldehyde dehydrogenase 2, and enolase 1 expression had a best AUC in predicting whether patients would receive local treatment of 0.92 (95% CI 0.89-0.94) in the training set, 0.85 (95% CI 0.77-0.94) in the test set, and 0.88 (95% CI 0.81-0.96) in the validation set.

Conclusion: Local treatment provided significant pain relief and improved QoL. There were no significant differences in reducing pain and improving QoL among training, test, and validation sets. The DT model was best at determining whether patients should receive local treatment. Our machine learning model can help guide clinicians to make local treatment decisions to reduce pain.

Trial Registration: Trial registration number ChiCRT-ROC-16009501.
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http://dx.doi.org/10.1007/s40122-021-00251-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8119531PMC
June 2021

TACC3 is a prognostic biomarker for kidney renal clear cell carcinoma and correlates with immune cell infiltration and T cell exhaustion.

Aging (Albany NY) 2021 03 10;13(6):8541-8562. Epub 2021 Mar 10.

Department of Immune-Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, P.R. China.

Growing evidence has demonstrated that transforming acidic coiled-coil protein 3 (TACC3), a member of the TACC family, may be involved in regulating cell mitosis, transcription, and tumorigenesis. However, the role of TACC3 in kidney renal clear cell carcinoma (KIRC) remains unknown. In this study, multiple databases were used to determine the pattern of TACC3 in KIRC. We found that high TACC3 expression was associated with poor overall survival (OS) in stage I, II, IV and grade 3 KIRC patients. Univariate and multivariate Cox regression analyses showed that TACC3 was an independent risk factor for OS among KIRC patients. Moreover, TACC3 expression correlated with immune cell infiltration levels of B cells, T cells (CD8+, CD4+, follicular helper, regulatory and gamma delta), total and resting natural killer cells, total and activated dendritic cells, and resting mast cells. Furthermore, T cell exhaustion markers, such as PD1, CTLA4, LAG3 and TIM-3 were highly expressed in TACC3 overexpressing tissues. In addition, GSEA analysis revealed that the role of TACC3 in KIRC may be closely linked to immune-associated pathways. Therefore, our study reveals that TACC3 is a prognostic biomarker for OS among KIRC patients and may be associated with immune cell infiltration and T cell exhaustion.
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http://dx.doi.org/10.18632/aging.202668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034911PMC
March 2021

Bioinformatics analysis and verification of gene targets for renal clear cell carcinoma.

Comput Biol Chem 2021 Jun 9;92:107453. Epub 2021 Feb 9.

Department of Immuno-oncology, The Fourth Hospital of Hebei Medical University, No.12 Jiankang Road Shijiazhuang, 050011, Hebei Province, China. Electronic address:

Background: It is estimated that there are 338,000 new renal-cell carcinoma releases every year in the world. Renal cell carcinoma (RCC) is a heterogeneous tumor, of which more than 70% is clear cell renal cell carcinoma (ccRCC). It is estimated that about 30% of new renal-cell carcinoma patients have metastases at the time of diagnosis. However, the pathogenesis of renal clear cell carcinoma has not been elucidated. Therefore, it is necessary to further study the pathogenesis of ccRCC.

Methods: Two expression profiling datasets (GSE68417, GSE71963) were downloaded from the GEO database. Differentially expressed genes (DEGs) between ccRCC and normal tissue samples were identified by GEO2R. Functional enrichment analysis was made by the DAVID tool. Protein-protein interaction (PPI) network was constructed. The hub genes were excavated. The clustering analysis of expression level of hub genes was performed by UCSC (University of California Santa Cruz) Xena database. The hub gene on overall survival rate (OS) in patients with ccRCC was performed by Kaplan-Meier Plotter. Finally, we used the ccRCC renal tissue samples to verify the hub genes.

Results: 1182 common DEGs between the two datasets were identified. The results of GO and KEGG analysis revealed that variations in were predominantly enriched in intracellular signaling cascade, oxidation reduction, intrinsic to membrane, integral to membrane, nucleoside binding, purine nucleoside binding, pathways in cancer, focal adhesion, cell adhesion molecules. 10 hub genes ITGAX, CD86, LY86, TLR2, TYROBP, FCGR2A, FCGR2B, PTPRC, ITGB2, ITGAM were identified. FCGR2B and TYROBP were negatively correlated with the overall survival rate in patients with ccRCC (P < 0.05). RT-qPCR analysis showed that the relative expression levels of CD86, FCGR2A, FCGR2B, TYROBP, LY86, and TLR2 were significantly higher in ccRCC samples, compared with the adjacent renal tissue groups.

Conclusions: In summary, bioinformatics technology could be a useful tool to predict the progression of ccRCC. In addition, there are DEGs between ccRCC tumor tissue and normal renal tissue, and these DEGs might be considered as biomarkers for ccRCC.
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http://dx.doi.org/10.1016/j.compbiolchem.2021.107453DOI Listing
June 2021

Superelastic TiCT MXene-Based Hybrid Aerogels for Compression-Resilient Devices.

ACS Nano 2021 Mar 26;15(3):5000-5010. Epub 2021 Feb 26.

Institute for Frontier Materials, Deakin University, Geelong, VIC 3216, Australia.

Superelastic aerogels with excellent electrical conductivity, reversible compressibility, and high durability hold great potential for varied emerging applications, ranging from wearable electronics to multifunctional scaffolds. In the present work, superelastic MXene/reduced graphene oxide (rGO) aerogels are fabricated by mixing MXene and GO flakes, followed by a multistep reduction of GO, freeze-casting, and finally an annealing process. By optimizing both the composition and reducing conditions, the resultant aerogel shows a reversible compressive strain of 95%, surpassing all current reported values. The conducting MXene/rGO network provides fast electron transfer and stable structural integrity under compression/release cycles. When assembled into compressible supercapacitors, 97.2% of the capacitance was retained after 1000 compression/release cycles. Moreover, the high conductivity and porous structure also enabled the fabrication of a piezoresistive sensor with high sensitivity (0.28 kPa), wide detection range (up to 66.98 kPa), and ultralow detection limit (∼60 Pa). It is envisaged that the superelasticity of MXene/rGO aerogels offers a versatile platform for utilizing MXene-based materials in a wide array of applications including wearable electronics, electromagnetic interference shielding, and flexible energy storage devices.
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http://dx.doi.org/10.1021/acsnano.0c09959DOI Listing
March 2021

Increased grey matter volume and associated resting-state functional connectivity in chronic spontaneous urticaria: A structural and functional MRI study.

J Neuroradiol 2021 Jun 4;48(4):236-242. Epub 2021 Feb 4.

Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA 02129, USA; Harvard Medical School, Boston, MA 02125, USA.

Background And Purpose: Chronic itch is one of the most common irritating sensations, yet its mechanisms have not been fully elucidated. Although some studies have revealed relationships between itching and brain function, the structural changes in the brain induced by chronic itching, such as those accompanying chronic spontaneous urticaria (CSU), remain unclear. In this study, we aimed to explore the potential changes in brain structure and the associated functional circuitry in CSU patients to generate insights to aid chronic itch management.

Methods: Forty CSU patients and forty healthy controls (HCs) were recruited. Seven-day urticaria activity score (UAS7) values were collected to evaluate clinical symptoms. Voxel-based morphometry (VBM) and seed-based resting-state functional connectivity (rs-FC) analysis were used to assess structural changes in the brain and associated changes in functional circuitry.

Results: Compared with HCs, CSU patients had significantly increased grey matter (GM) volume in the right premotor cortex, left fusiform cortex, and cerebellum. UAS7 values were positively associated with GM volume in the left fusiform cortex. In CSU patients relative to HCs, the left fusiform cortex as extracted by VBM analysis demonstrated decreased functional connectivity with the right orbitofrontal cortex, medial prefrontal cortex (mPFC), premotor cortex, primary motor cortex (MI), and cerebellum and increased functional connectivity with the right posterior insular cortex, primary somatosensory cortex (SI), and secondary somatosensory cortex (SII). The left cerebellum as extracted from VBM analysis demonstrated decreased functional connectivity with the right supplementary motor area (SMA) and MI in CSU patients relative to HCs.

Conclusions: Our findings indicate that patients suffering from chronic itching conditions, such as CSU, are likely to demonstrate altered GM volume in some brain regions. These changes may affect not only the sensorimotor area but also brain regions associated with cognitive function.
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http://dx.doi.org/10.1016/j.neurad.2021.01.011DOI Listing
June 2021

Role of key amino acids in the transmembrane domain of the Newcastle disease virus fusion protein.

Biosci Trends 2021 Mar 27;15(1):16-23. Epub 2021 Jan 27.

Department of Virology, School of Public Health, Cheeloo College of Medicine, Shandong University, Ji'nan, Shandong, China.

Newcastle disease (ND), caused by the Newcastle disease virus (NDV), is transmitted by poultry with severe infectivity and a high fatality rate. The fusion (F) protein on the NDV envelope facilitates the merger of the viral and host cell membranes with the help of the homologous hemagglutinin-neuraminidase protein (HN). The transmembrane (TM) domains of viral fusion proteins are typically required for fusion, but the key amino acids in NDV F TM domains have not been identified. Site-directed mutagenesis was utilized to change the conserved amino acids at 500, 501, 502, 505, 510, 513, 516, 519, and 520 to alanine. It was found that mutants L519 and V520 had an interrupted protein expression, decreased to below 10%, and mutants A500, I505, V513, and V516 had a hypoactive impact on fusion activity, decreased to 85.38%, 67.05%, 55.38% and 51.13% of wt F, respectively. The results indicated that the TM domain plays a vital part in the fusion activity of the NDV F protein.
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http://dx.doi.org/10.5582/bst.2020.03317DOI Listing
March 2021

Boosting the Electrocatalysis of MXenes by Plasmon-Induced Thermalization and Hot-Electron Injection.

Angew Chem Int Ed Engl 2021 Apr 10;60(17):9416-9420. Epub 2021 Mar 10.

College of Chemical Engineering, Beijing University of Chemical Technology, Beijing, 100029, China.

The MXenes attract great interest in catalytic and energy applications but suffer from inferior redox activity. An efficient strategy is presented to boost the intrinsic electrochemical activity of MXenes for electrocatalysis in various chemical environments by utilizing their plasmonic response to electromagnetic waves. The resulting significant thermoplasmonic effect lowers the endothermic enthalpy and potential barrier to the hydrogen evolution reaction (HER) in the Vis/near-IR region. Simultaneous hot-electron injection in a prolonged sub-femtosecond to picosecond timescale also remarkably facilitates interfacial charge transfer and decreases the activation energy of the reaction. Both effects boost the HER activity of various types of MXenes over fivefold with improved kinetics and Faradaic efficiency over a broad pH range.
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http://dx.doi.org/10.1002/anie.202016181DOI Listing
April 2021

[Relationship between the timing of initiation of continuous renal replacement therapy and the prognosis of patients with sepsis-associated acute kidney injury].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2020 Nov;32(11):1352-1355

Department of Critical Care Medicine, Ningbo First Hospital, Ningbo 315010, Zhejiang, China. Corresponding author: Zhu Jianhua, Email:

Objective: To investigate the relationship between the timing of initiation of continuous renal replacement therapy (CRRT) and the prognosis of patients with sepsis associated-acute kidney injury (SA-AKI).

Methods: The clinical data of SA-AKI patients undergoing CRRT in intensive care unit (ICU) of Ningbo First Hospital from January 2017 to November 2019 were retrospectively analyzed. According to the guidelines for Kidney Disease: Improving Global Outcomes (KDIGO), patients with AKI who started CRRT in stage 1 or 2 were included in the early treatment group, and those started CRRT in stage 3 were included in the late treatment group. The general clinical data, length of ICU stay, total length of hospital stay, 28-day and 90-day mortality, CRRT duration, 28-day and 90-day renal replacement therapy (RRT) disengagement rate, 28-day and 90-day RRT dependence rate in the survival patients were compared between the two groups. Kaplan-Meier survival analysis was performed to assess the 90-day cumulative survival rate of patients with SA-AKI between two groups.

Results: A total of 244 SA-AKI patients were enrolled in this study, including 71 patients in the early treatment group and 173 patients in the late treatment group. There were no significant differences in age, gender composition, acute physiology and chronic health evaluation II (APACHE II), proportion of surgical patients, infection site and anticoagulation program between the two groups. The CRRT duration in the early group was significantly shorter than that in the late group [hours: 26.0 (12.0, 49.0) vs. 41.0 (20.8, 87.0), P < 0.01], but there were no significant differences in the length of ICU stay [days: 9.0 (4.0, 15.0) vs. 10.0 (4.5, 18.0)], total length of hospital stay [days: 17.0 (10.0, 30.0) vs. 18.0 (10.0, 32.0)], 28-day mortality (45.1% vs. 48.0%), 90-day mortality (46.4% vs. 51.4%), 28-day RRT disengagement rate (49.3% vs. 45.1%) and 90-day RRT disengagement rate (52.1% vs. 47.4%) between the early treatment group and late treatment group (all P > 0.05). There were also no significant differences in 28-day RRT dependence rate [10.3% (4/39) vs. 13.3% (12/90)] and 90-day RRT dependence rate [2.6% (1/38) vs. 2.4% (2/84)] between early treatment group and late treatment group (both P > 0.05). Kaplan-Meier survival analysis suggested that there was no significant difference in the 90-day cumulative survival rate between two groups (Log-Rank test: χ = 0.791, P = 0.374).

Conclusions: Early initiation of CRRT treatment in SA-AKI patients can reduce the duration of CRRT, but has no effect on length of ICU stay, total length of hospital stay, renal function recovery and mortality. At present, the optimal timing for initiation of CRRT in patients with SA-AKI remains unknown.
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http://dx.doi.org/10.3760/cma.j.cn121430-20200304-00206DOI Listing
November 2020

Research trends in pharmacological modulation of tumor-associated macrophages.

Clin Transl Med 2021 01;11(1):e288

The Research Center for Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.

As one of the most abundant immune cell populations in the tumor microenvironment (TME), tumor-associated macrophages (TAMs) play important roles in multiple solid malignancies, including breast cancer, prostate cancer, liver cancer, lung cancer, ovarian cancer, gastric cancer, pancreatic cancer, and colorectal cancer. TAMs could contribute to carcinogenesis, neoangiogenesis, immune-suppressive TME remodeling, cancer chemoresistance, recurrence, and metastasis. Therefore, reprogramming of the immune-suppressive TAMs by pharmacological approaches has attracted considerable research attention in recent years. In this review, the promising pharmaceutical targets, as well as the existing modulatory strategies of TAMs were summarized. The chemokine-chemokine receptor signaling, tyrosine kinase receptor signaling, metabolic signaling, and exosomal signaling have been highlighted in determining the biological functions of TAMs. Besides, both preclinical research and clinical trials have suggested the chemokine-chemokine receptor blockers, tyrosine kinase inhibitors, bisphosphonates, as well as the exosomal or nanoparticle-based targeting delivery systems as the promising pharmacological approaches for TAMs deletion or reprogramming. Lastly, the combined therapies of TAMs-targeting strategies with traditional treatments or immunotherapies as well as the exosome-like nanovesicles for cancer therapy are prospected.
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http://dx.doi.org/10.1002/ctm2.288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805405PMC
January 2021

L. Suppresses Triple-Negative Breast Cancer Metastasis by Inhibiting Late-Phase Autophagy via Hif-1α/Caveolin-1 Signaling.

Front Pharmacol 2020 14;11:591400. Epub 2020 Dec 14.

Integrative Research Laboratory of Breast Cancer, The Second Clinical College, Guangzhou University of Chinese Medicine, Guangdong, China.

L. (SA) is a common herb for cancer treatment in the clinic, particularly during the consolidation phase to prevent occurrence or metastasis. Nevertheless, there are limited studies reporting the molecular mechanisms about its anti-metastatic function. It is well demonstrated that autophagy is one of the critical mechanisms accounting for metastasis and anti-cancer pharmacological actions of Chinese herbs. On the threshold, the regulatory effects and molecular mechanisms of SA in suppressing autophagy-related breast cancer metastasis were investigated in this study. findings demonstrated that SA potently suppressed the proliferation, colony formations well as metastasis process in triple-negative breast cancer. Network and biological analyses predicted that SA mainly targeted caveolin-1 (Cav-1) to induce anti-metastatic effects, and one of the core mechanisms was regulation of autophagy. Further experiments-including western blotting, transmission electron microscopy, GFP-mRFP-LC3 immunofluorescence, and lysosomal-activity detection-validated SA as a potent late-stage autophagic inhibitor by increasing microtubule-associated light chain 3-II (LC3-II) conversion, decreasing acidic vesicular-organelle formation, and inducing lysosomal dysfunction even under conditions of either starvation or hypoxia. Furthermore, the anti-autophagic and anti-metastatic activity of SA was Cav-1-dependent. Specifically, Cav-1 knockdown significantly facilitated SA-mediated inhibition of autophagy and metastasis. Furthermore, hypoxia inducible factor-1α (Hif-1α) overexpression attenuated the SA-induced inhibitory activities on Cav-1, autophagy, and metastasis, indicating that SA may have inhibited autophagy-related metastasis Hif-1α/Cav-1 signaling. In both mouse breast cancer xenograft and zebrafish xenotransplantation models, SA inhibited breast cancer growth and inhibited late-phase autophagy , which was accompanied by suppression of Hif-1α/Cav-1 signaling and the epithelial-mesenchymal transition. Overall, our findings not only indicate that SA acts as a novel late-phase autophagic inhibitor with anti-metastatic activities in triple-negative breast cancer, but also highlight Cav-1 as a regulator in controlling late-phase autophagic activity.
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http://dx.doi.org/10.3389/fphar.2020.591400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768086PMC
December 2020

Dynamic Behaviour of Bridge Girders with Trapezoidal Profiled Webs Subjected to Moving Loads.

Materials (Basel) 2020 Dec 24;14(1). Epub 2020 Dec 24.

Innovation Design Department, Shenzhen Municipal Engineering Design and Research Institute Co., Ltd., 3007 Sungang W Rd, Futian District, Shenzhen 518029, China.

The aim of this study is to find out the degradation of dynamic behaviour of bridge girders with trapezoidal profiled webs when subjected to different vehicle moving loads. Finite element modelling based parametric analysis is demonstrated to be desirable in capturing the dynamic deflection and stress state of critical structural details of girders. The model is validated in the modal analysis through a comparison with theoretical eigenfrequencies. The vibration characteristics are shown to be significantly affected by the corrugation details. The structural service life results of analysed bridge girders are in close agreement with experimental data. It is shown that the dynamic nodal velocity and deflection of analysed bridge girders are greatly affected by the magnitude of the load corresponding to the overload of the vehicle in contrast to the vehicle travel speed. Similar observations can be made for the fatigue life prediction analysis related to the crack initiation when unfavourable effects of the overload vehicle are concerned. Presented analytical results using a fracture mechanics approach could be taken as a good basis for the service life assessment of related bridges with the desired level of performance or functionality.
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http://dx.doi.org/10.3390/ma14010038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795918PMC
December 2020

Coupling Liquid Chromatography and Tandem Mass Spectrometry to Electrophoresis for In-Depth Analysis of Glycosaminoglycan Drugs: Heparin and the Multicomponent Sulodexide.

Anal Chem 2021 01 28;93(3):1433-1442. Epub 2020 Dec 28.

National Glycoengineering Research Center, Shandong Provincial Key Laboratory of Carbohydrate Chemistry and Glycobiology, Shandong University, Qingdao 266237, China.

Glycosaminoglycans (GAGs) contribute to the treatment of many human diseases, especially in the field of thrombosis, because of their anticoagulant activity. GAGs interrupt the coagulation process by interacting with multiple coagulation factors through defined sequences within their linear and negatively charged chains, which are not fully elucidated. Numerous methods have been developed to characterize the structure of pharmaceutical GAGs, including or administered heparin and orally administered sulodexide. However, most currently available methods only focus on the oligosaccharide portion or analyze the whole mixture because longer-chain polysaccharides are extremely difficult to resolve by chromatographic separation. We have established two novel electrophoresis-mass spectrometry methods to provide a panoramic view of the structures of pharmaceutical GAGs. In the first method, an in-gel digestion procedure was developed to recover GAGs from the polyacrylamide gels, while in the second method, a strong anion exchange ultrafiltration procedure was developed to extract multiple GAG species from the agarose gels. Both procedures are compatible with liquid chromatography-tandem mass spectrometry, and structural information, such as disaccharide composition and chain length, can be revealed for each GAG fraction. The applications of these two methods on analysis of two different GAG drugs, heparin and sulodexide, were demonstrated. The current study offers the first robust tool to directly elucidate the structure of larger GAG chains with more biological importance rather than obtaining a vague picture of all chains as a mixture, which is fundamental for better understanding the structure-activity relationship and quality control of the GAG drugs.
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http://dx.doi.org/10.1021/acs.analchem.0c03330DOI Listing
January 2021

Factors influencing social distancing to prevent the community spread of COVID-19 among Chinese adults.

Prev Med 2021 02 31;143:106385. Epub 2020 Dec 31.

School of Public Administration, Dongbei University of Finance and Economics, Dalian, China. Electronic address:

The global outbreak of the coronavirus disease 2019 (COVID-19) in 2020 has been an international public health threat. Early strong social distancing efforts is needed to stop transmission of the virus. The purpose of the present study is to identify individual and environmental factors related to individuals' compliance with the recommended social distancing, as well as the moderating role of social media in influencing individuals' implementation of social distancing. A total of 2130 Chinese adults were surveyed in March 2020 during the COVID-19 pandemic. Logistic regression analyses were performed to ascertain the predictors of social distancing. Overall, the majority of respondents (95.6%) reported compliance with social distancing. Women were more likely to practice social distancing compared to men (odds ratio [OR] = 3.12, 95% confidence interval [CI] = 1.93-5.02). Psychological distress, depressive symptoms, and social media were significant predictors of social distancing after controlling for other individual and environmental factors. Social media moderated the effects of psychological distress on social distancing (OR = 0.96, 95% CI = 0.94-0.99). Findings from the study indicates that mental health status and social media are influential factors of social distancing, which have significant implications in enhancing the effectiveness of prevention strategies to contain the spread of COVID-19.
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http://dx.doi.org/10.1016/j.ypmed.2020.106385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774485PMC
February 2021

Blockade of TRIM59 enhances esophageal cancer cell chemosensitivity to cisplatin by upregulating p53.

Oncol Lett 2021 Jan 3;21(1). Epub 2020 Nov 3.

Third Department of Thoracic Surgery, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.

Human esophageal cancer (hESC) cell motility adopts various modes, resulting in hESC progression and poor survival. However, how tripartite motif 59 (TRIM59), as the ubiquitination machinery, participates in hESC metastasis is not completely understood. The results indicated that TRIM59 was aberrantly upregulated in hESC tissues compared with adjacent healthy esophageal tissues, which was associated with poor survival and advanced TNM state among patients with hESC. Moreover, patients with hESC with higher TRIM59 expression displayed undetectable p53 expression, which contributed to enhanced progression and motility of hESC. At the molecular level, TRIM59 was indicated to be an E3 putative ubiquitin ligase that targeted the p53 protein, leading to increased degradation of p53, which resulted in decreased chemosensitivity to cisplatin. TRIM59 knockdown reduced TRIM59 expression, increased p53 protein expression, and decreased hESC cell viability, clone formation and migration compared with the small interfering RNA negative control (siNC) group. Furthermore, hESC cell lines were more sensitive to cisplatin in the TRIM59-knockdown group compared with the siNC group. The results indicated a relationship between TRIM59, p53 and the chemosensitivity of cisplatin. The present study suggested that TRIM59 may serve as a promising prognostic indicator for patients with hESC.
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http://dx.doi.org/10.3892/ol.2020.12267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7681221PMC
January 2021
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