Publications by authors named "Xiao Han"

1,507 Publications

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Application of Carbon Ion and Its Sensitizing Agent in Cancer Therapy: A Systematic Review.

Front Oncol 2021 5;11:708724. Epub 2021 Jul 5.

School of Life Science, Institute of Engineering Medicine, Beijing Institute of Technology, Beijing, China.

Carbon ion radiation therapy (CIRT) is the most advanced radiation therapy (RT) available and offers new opportunities to improve cancer treatment and research. CIRT has a unique physical and biological advantage that allow them to kill tumor cells more accurately and intensively. So far, CIRT has been used in almost all types of malignant tumors, and showed good feasibility, safety and acceptable toxicity, indicating that CIRT has a wide range of development and application prospects. In addition, in order to improve the biological effect of CIRT, scientists are also trying to investigate related sensitizing agents to enhance the killing ability of tumor cells, which has attracted extensive attention. In this review, we tried to systematically review the rationale, advantages and problems, the clinical applications and the sensitizing agents of the CIRT. At the same time, the prospects of the CIRT in were prospected. We hope that this review will help researchers interested in CIRT, sensitizing agents, and radiotherapy to understand their magic more systematically and faster, and provide data reference and support for bioanalysis, clinical medicine, radiotherapy, heavy ion therapy, and nanoparticle diagnostics.
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http://dx.doi.org/10.3389/fonc.2021.708724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287631PMC
July 2021

LncRNA PVT1 promotes the progression of ovarian cancer by activating TGF-β pathway via miR-148a-3p/AGO1 axis.

J Cell Mol Med 2021 Jul 21. Epub 2021 Jul 21.

Department of Obstetrics and Gynaecology, Changzheng Hospital, Naval Medical University, Shanghai, China.

Ovarian cancer is a lethal gynaecologic malignancy with poor diagnosis and prognosis. The long non-coding RNA plasmacytoma variant translocation1 (PVT1) and argonaute 1 (AGO1) are associated with carcinogenesis and chemoresistance; however, the relationship between PVT1 and AGO1 and the downstream mechanisms in ovarian cancer remains poorly known. PVT1 and AGO1 expression was assessed through RT-qPCR and Western blotting in both human tissues and cell lines. The viability and proliferation of ovarian cancer cells were determined by CCK-8 assay and TUNEL assay in vitro and immunohistochemistry in vivo. Cell invasion and migration were investigated through transwell and wound-healing assays. The roles and mechanisms of AGO1 on cell functions were further probed via gain- and loss-of-function analysis. We reveal that PVT1 expression was significantly increased in ovarian cancer tissues which is associated with advanced FIGO stage, lymph-node metastasis, poor survival rate, and high expression of AGO1. PVT1 or AGO1 knockdown significantly reduced the cell viability and increased the cell apoptosis and inhibited ovarian tumour growth and proliferation. Furthermore, we discovered that PVT1 up-regulated the expression of AGO1 and thus regulated the transforming growth factor-β (TGF-β) pathway to promote ovarian cancer progression through sponging miR-148a-3p. Additionally, the activation of ERK1/2, smad2 and smad4 is observed to be related to the PVT1/miR-148a-3p/AGO1/TGF-β pathway-induced cascades. Taken together, the present study reveals that PVT1/miR-148a/AGO1 axis plays an important role in the progression of ovarian cancer and emphasize the potential as a target of value for ovarian cancer therapy.
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http://dx.doi.org/10.1111/jcmm.16700DOI Listing
July 2021

A deep learning approach to automate whole-genome prediction of diverse epigenomic modifications in plants.

New Phytol 2021 Jul 20. Epub 2021 Jul 20.

Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing, 100081, China.

Epigenetic modifications function in gene transcription, RNA metabolism, and other biological processes. However, multiple factors currently limit the scientific utility of epigenomic datasets generated for plants. Here, using deep-learning approaches, we developed a Smart Model for Epigenetics in Plants (SMEP) to predict six types of epigenomic modifications: DNA 5-methylcytosine (5mC) and N6-methyladenosine (6mA) methylation, RNA N6-methyladenosine (m A) methylation, and three types of histone modification. Using the datasets from the japonica rice Nipponbare, SMEP achieved 95% prediction accuracy for 6mA, and also achieved around 80% for 5mC, m A, and the three types of histone modification based on the 10-fold cross-validation. Additionally, >95% of the 6mA peaks detected after a heat-shock treatment were predicted. We also successfully applied the SMEP for examining epigenomic modifications in indica rice 93-11 and even the B73 maize line. Taken together, we show that the deep-learning-enabled SMEP can reliably mine epigenomic datasets from diverse plants to yield actionable insights about epigenomic sites. Thus, our work opens new avenues for the application of predictive tools to facilitate functional research, and will almost certainly increase the efficiency of genome engineering efforts.
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http://dx.doi.org/10.1111/nph.17630DOI Listing
July 2021

Porcine circovirus 2 manipulates PERK-ERO1α axis of endoplasmic reticulum in favor of its replication by derepressing viral DNA from HMGB1 sequestration within nuclei.

J Virol 2021 Jul 21:JVI0100921. Epub 2021 Jul 21.

Institute of Preventive Veterinary Medicine and Zhejiang Provincial Key Laboratory of Preventive Veterinary Medicine, Zhejiang University, Hangzhou, Zhejiang, CHINA.

Porcine circovirus type 2 (PCV2) causes several disease syndromes in grower pigs. PCV2 infection triggers endoplasmic reticulum (ER) stress, autophagy and oxidative stress, all of which support PCV2 replication. We have recently reported that nuclear HMGB1 is an anti-PCV2 factor by binding to viral genomic DNA. However, how PCV2 manipulates host cell responses to favor its replication has not been explored. Here, we demonstrate that PCV2 infection increased expression of ERO1α, generation of ROS and nucleocytoplasmic migration of HMGB1 via PERK activation in PK-15 cells. Inhibition of PERK or ERO1α repressed ROS production in PCV2-infected cells and increased HMGB1 retention within nuclei. These findings indicate that PCV2-induced activation of the PERK-ERO1α axis would lead to enhanced generation of ROS sufficient to decrease HMGB1 retention in the nuclei, thus derepressing viral DNA from HMGB1 sequestration. The viral Rep and Cap proteins were able to induce PERK-ERO1α-mediated ROS accumulation. Cysteine residues 107 and 305 of Rep or 108 of Cap played important roles in PCV2-induced PERK activation and distribution of HMGB1. Of the mutant viruses, only the mutant PCV2 with substitution of all three cysteine residues failed to activate PERK with reduced ROS generation and decreased nucleocytoplasmic migration of HMGB1. Collectively, this study offers novel insight into the mechanism of enhanced viral replication in which PCV2 manipulates ER to perturb its redox homeostasis via the PERK-ERO1α axis and the ER-sourced ROS from oxidative folding is sufficient to reduce HMGB1 retention in the nuclei, hence the release of HMGB1-bound viral DNA for replication. Considering the fact that clinical PCVAD mostly results from activation of latent PCV2 infection by confounding factors such as co-infection or environmental stresses, we propose that such confounding factors might impose oxidative stress to the animals where PCV2 in infected cells might utilize the elevated ROS to promote HMGB1 migration out of nuclei in favor of its replication. An animal infection model with a particular stressor could be approached with or without antioxidant treatment to examine the relationship among the stressor, ROS level, HMGB1 distribution in target tissues, virus replication and severity of PCVAD. This will help decide the use of antioxidants in the feeding regime on pig farms that suffer from PCVAD. Further investigation could examine if similar strategies are employed by DNA viruses, such as PCV3 and BFDV and if there is cross-talk among ER stress, autophagy/mitophagy and mitochondria-sourced ROS in favor of PCV2 replication.
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http://dx.doi.org/10.1128/JVI.01009-21DOI Listing
July 2021

Can AI-assisted microscope facilitate breast HER2 interpretation? A multi-institutional ring study.

Virchows Arch 2021 Jul 19. Epub 2021 Jul 19.

Department of Pathology, The Fourth Hospital of Hebei Medical University, No. 12 Jiankang Road, Shijiazhuang, 050011, Hebei, China.

The level of human epidermal growth factor receptor-2 (HER2) protein and gene expression in breast cancer is an essential factor in judging the prognosis of breast cancer patients. Several investigations have shown high intraobserver and interobserver variability in the evaluation of HER2 staining by visual examination. In this study, we aim to propose an artificial intelligence (AI)-assisted microscope to improve the HER2 assessment accuracy and reliability. Our AI-assisted microscope was equipped with a conventional microscope with a cell-level classification-based HER2 scoring algorithm and an augmented reality module to enable pathologists to obtain AI results in real time. We organized a three-round ring study of 50 infiltrating duct carcinoma not otherwise specified (NOS) cases without neoadjuvant treatment, and recruited 33 pathologists from 6 hospitals. In the first ring study (RS1), the pathologists read 50 HER2 whole-slide images (WSIs) through an online system. After a 2-week washout period, they read the HER2 slides using a conventional microscope in RS2. After another 2-week washout period, the pathologists used our AI microscope for assisted interpretation in RS3. The consistency and accuracy of HER2 assessment by the AI-assisted microscope were significantly improved (p < 0.001) over those obtained using a conventional microscope and online WSI. Specifically, our AI-assisted microscope improved the precision of immunohistochemistry (IHC) 3 + and 2 + scoring while ensuring the recall of fluorescent in situ hybridization (FISH)-positive results in IHC 2 + . Also, the average acceptance rate of AI for all pathologists was 0.90, demonstrating that the pathologists agreed with most AI scoring results.
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http://dx.doi.org/10.1007/s00428-021-03154-xDOI Listing
July 2021

The effect of endometrial scratch on pregnancy outcomes of frozen-thawed embryo transfer: a propensity score-matched study.

Authors:
Xiao Han Linli Hu

Gynecol Endocrinol 2021 Jul 19:1-6. Epub 2021 Jul 19.

Reproductive Medical Center, Henan Province Key Laboratory of Reproduction and Genetics,The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Aims: To study the effect of endometrial scratch (ES) performed on Days 2 to 5 of the menstrual cycle on pregnancy outcomes of frozen-thawed embryo transfer (FET).

Materials And Methods: We conducted a retrospective study including 5769 women undergoing FET from January 2018 to August 2019. The endometrial scratching group (group ES) consisted of 827 patients and the control group (group non-ES) comprised 4942 patients. A propensity score matching (PSM) method using the nearest neighbor matching at a proportion of 1:1 was performed. Subsequently, we compared the pregnancy outcomes of each group after PSM.

Results: After PSM, there were significant differences in implantation (36.1% vs. 47.0%,  = .005), clinical pregnancy (45.4% vs. 58.3%,  = .007), and live birth (33.5% vs. 47.2%,  = .003) rates in matched patients with two previous implantation failures. In the matched patients with at least three previous implantation failures, we also detected increase rates of implantation (31.0% versus 40.1%,  = .028), clinical pregnancy (39.8% versus 57.0%,  = .019), live birth (32.3% versus 47.3%,  = .036). In contrast, no significant difference in pregnancy outcomes was found in women with no previous implantation failure or only one failure.

Conclusions: Endometrial scratch on day 2 to day 5 of the menstrual cycle in women with at least two previous implantation failures who underwent FET increased their implantation, clinical pregnancy, and live birth rates, and did not increase miscarriage or ectopic pregnancy rates compared to the non-ES group.
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http://dx.doi.org/10.1080/09513590.2021.1953464DOI Listing
July 2021

Outcomes of switching from crizotinib to alectinib in patients with advanced non-small cell lung cancer with anaplastic lymphoma kinase fusion.

Ann Transl Med 2021 Jun;9(12):1014

Department of Medical Oncology, Shanghai Pulmonary Hospital &Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China.

Background: Alectinib and crizotinib have been approved as first-line therapies for advanced non-small cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK) gene fusion. However, the therapeutic efficacy and side effects are still largely unknown of patients who switched to next-generation ALK tyrosine kinase inhibitors (ALK-TKIs), such as alectinib, after experiencing no disease progression with initial crizotinib treatment.

Methods: This prospective real-world study enrolled patients who were treated with alectinib after experiencing no disease progression with initial crizotinib treatment. The patients' baseline characteristics, objective response rate (ORR) of crizotinib and alectinib, size change of target tumor lesions, treatment regimen and adverse events (AEs) were collected and analyzed.

Results: The study included 53 patients, the majority of whom (96.2%) had non-squamous NSCLC. The median age was 51 (range, 31-80) years old. The ORR of first-line crizotinib was 54.7%. The ORR of sequential alectinib was 73.6%, and 90.5% of patients showed further tumor shrinkage after the alectinib treatment. The median progression-free survival was not reached, and 90.5% of patients were still enrolled in the study at the last follow-up. Among them, 34.0% of patients switched to alectinib treatment due to the toxicity. Crizotinib was associated with a higher frequency of AEs of grades 3 and 4 than alectinib (15.1% 0%). Neither group had any AEs resulting in death.

Conclusions: Switching to alectinib might be an option for patients who do not experience disease progression with initial crizotinib therapy, and may promote better treatment compliance.
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http://dx.doi.org/10.21037/atm-21-2769DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267309PMC
June 2021

SRC-3 Deficiency Exacerbates Neurological Deficits in a Mouse Model of Intracerebral Hemorrhage: Role of Oxidative Stress.

Neurochem Res 2021 Jul 15. Epub 2021 Jul 15.

Department of Neurology, The Second Xiangya Hospital, Central South University, No. 139 Renmin Road, Changsha, 410011, Hunan, China.

Intracerebral hemorrhage (ICH) causes long term neurological abnormality or death. Oxidative stress is closely involved in ICH mediated brain damage. Steroid receptor cofactor 3 (SRC-3), a p160 family member, is widely expressed in the brain and regulates transactivation of Nrf2, a key component of antioxidant response. Our study aims to test if SRC-3 is implicated in ICH mediated brain injury. We first examined levels of SRC-3 and oxidative stress in the brain of mice following ICH and analyzed their correlation. Then ICH was induced in wild type (WT) and SRC-3 knock out mice and how SRC-3 deletion affected ICH induced brain damage, oxidative stress and behavioral outcome was assessed. We found that SRC-3 mRNA and protein expression levels were reduced gradually after ICH induction in WT mice along with an increase in oxidative stress levels. Correlation analysis revealed that SRC-3 mRNA levels negatively correlated with oxidative stress. Deletion of SRC-3 further increased ICH induced brain edema, neurological deficit score and oxidative stress and exacerbated ICH induced behavioral abnormality including motor dysfunction and cognitive impairment. Our findings suggest that SRC-3 is involved in ICH induced brain injury, probably through modulation of oxidative stress.
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http://dx.doi.org/10.1007/s11064-021-03399-7DOI Listing
July 2021

Predictors for intraoperative heart failure in children undergoing foreign-body removal.

Medicine (Baltimore) 2021 Jul;100(28):e26626

Department of Otolaryngology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.

Abstract: This study aimed to determine the predictors for intraoperative heart failure (HF) in children undergoing foreign-body removal. The clinical data of all children with tracheobronchial foreign-body aspiration admitted to the First, Second, and Fourth Affiliated Hospitals of Harbin Medical University between January 1996 and September 2018 were analyzed. The variables with significant difference in univariate analysis were involved into the multivariate Logistic model to determine the predictors for intraoperative tachycardia. In total, 300 tracheobronchial foreign-body aspiration children were eligible for the study, among whom 60 cases (20%) suffered from HF during the operation. Between the children HF and those without HF, the differences were pronounced in history of allergy, history of asthma, congenital heart disease, preoperative respiratory infection, retention time of foreign bodies, duration of operation, and poor anesthesia effect (P < .05). Multivariate analysis results showed that history of allergy (odds ratio [OR]: 1.395, 95% confidence interval [95% CI]: 1.202-1.620, P < .001), congenital heart disease [OR: 3.071, 95% CI: 1.141-8.264, P < .001], preoperative respiratory infection [OR: 2.345, 95% CI: 1.027-5.355, P = .043], retention time of foreign bodies [OR: 1.013, 95% CI: 1.010-1.016, P < .001], duration of operation [OR: 1.030, 95% CI: 1.027-1.033, P < .001], and poor anesthesia effect [OR: 1.125, 95% CI: 1.117-1.134, P < .001] were identified as the influencing factors for intraoperative HF. In conclusions, for children undergoing foreign-body removal, history of allergy, congenital heart disease, preoperative respiratory infection, retention time of foreign bodies, duration of operation, and poor anesthesia effect are associated with an increased risk of intraoperative HF.
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http://dx.doi.org/10.1097/MD.0000000000026626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284771PMC
July 2021

N6-methyladenosine Demethylase FTO Induces the Dysfunctions of Ovarian Granulosa Cells by Upregulating Flotillin 2.

Reprod Sci 2021 Jul 12. Epub 2021 Jul 12.

Department of Gynecology, The First Hospital of Jilin University, No. 71, Xinmin Street, Changchun, 130021, Jilin, China.

Polycystic ovarian syndrome (PCOS) is often accompanied by overweight/obesity and insulin resistance. The dysfunctions of ovarian granulosa cells (GCs) are closely linked with the pathogenesis of PCOS. Fat mass and obesity-associated gene (FTO), an N6-methyladenosine (m6A) demethylase, has been reported to be implicated in the risks and insulin resistance of PCOS. However, the roles of FTO in the development of GCs along with its m6A-related regulatory mechanisms are poorly defined. Cell proliferative ability was detected by MTT assay. Cell apoptotic rate was measured via flow cytometry. Insulin resistance was assessed by GLUT4 transport potential. The mRNA and protein levels of FTO and flotillin 2 (FLOT2) were determined by RT-qPCR and western blot assays, respectively. FLOT2 was screened out to be a potential FTO target through differential expression analysis for the GSE95728 dataset and target prediction analysis by POSTAR2 and STARBASE databases. The interaction between FTO and FLOT2 was analyzed by RNA immunoprecipitation (RIP) assay. The effect of FTO upregulation on FLOT2 m6A level was measured by methylated RIP (meRIP) assay. FLOT2 mRNA stability was examined by actinomycin D assay. FTO overexpression facilitated cell proliferation, hindered cell apoptosis, and induced insulin resistance in GCs. FTO promoted FLOT2 expression by reducing m6A level on FLOT2 mRNA and increasing FLOT2 mRNA stability. FLOT2 loss weakened the effects of FTO overexpression on cell proliferation/apoptosis and insulin resistance in GCs. FTO induced the dysfunctions of GCs by upregulating FLOT2, suggesting that FTO/FLOT2 might play a role in the pathophysiology of PCOS.
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http://dx.doi.org/10.1007/s43032-021-00664-6DOI Listing
July 2021

Bioinformatics analysis of differentially expressed genes and identification of an miRNA-mRNA network associated with entorhinal cortex and hippocampus in Alzheimer's disease.

Hereditas 2021 Jul 9;158(1):25. Epub 2021 Jul 9.

Department of Human Anatomy, Institute of Neurobiology, Medical School of Nantong University, 19 Qixiu Road, Nantong, 226001, Jiangsu, China.

Background: Alzheimer's disease (AD) is a fatal neurodegenerative disorder, and the lesions originate in the entorhinal cortex (EC) and hippocampus (HIP) at the early stage of AD progression. Gaining insight into the molecular mechanisms underlying AD is critical for the diagnosis and treatment of this disorder. Recent discoveries have uncovered the essential roles of microRNAs (miRNAs) in aging and have identified the potential of miRNAs serving as biomarkers in AD diagnosis.

Methods: We sought to apply bioinformatics tools to investigate microarray profiles and characterize differentially expressed genes (DEGs) in both EC and HIP and identify specific candidate genes and pathways that might be implicated in AD for further analysis. Furthermore, we considered that DEGs might be dysregulated by miRNAs. Therefore, we investigated patients with AD and healthy controls by studying the gene profiling of their brain and blood samples to identify AD-related DEGs, differentially expressed miRNAs (DEmiRNAs), along with gene ontology (GO) analysis, KEGG pathway analysis, and construction of an AD-specific miRNA-mRNA interaction network.

Results: Our analysis identified 10 key hub genes in the EC and HIP of patients with AD, and these hub genes were focused on energy metabolism, suggesting that metabolic dyshomeostasis contributed to the progression of the early AD pathology. Moreover, after the construction of an miRNA-mRNA network, we identified 9 blood-related DEmiRNAs, which regulated 10 target genes in the KEGG pathway.

Conclusions: Our findings indicated these DEmiRNAs having the potential to act as diagnostic biomarkers at an early stage of AD.
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http://dx.doi.org/10.1186/s41065-021-00190-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8272337PMC
July 2021

Porcine epidemic diarrhea virus inhibits HDAC1 expression to facilitate its replication via binding of its nucleocapsid protein to host transcription factor Sp1.

J Virol 2021 Jul 7:JVI0085321. Epub 2021 Jul 7.

Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, China.

Porcine epidemic diarrhea virus (PEDV) is an enteric coronavirus causing acute intestinal infection in pigs, with high mortality often seen in neonatal pigs. The newborns rely on innate immune responses against invading pathogens because of lacking adaptive immunity. However, how PEDV disables the innate immunity of newborns towards severe infection remains unknown. We found that PEDV infection led to reduced expression of histone deacetylases (HDACs), especially HDAC1 in porcine IPEC-J2 cells. HDACs are considered as important regulators of innate immunity. We hypothesized that PEDV might interact with certain host factors to regulate HDAC1 expression in favor of its replication. We show that HDAC1 acted as a negative regulator of PEDV replication in IPEC-J2 cells, as shown by chemical inhibition, gene knockout and overexpression. A GC-box () within the promoter region was identified for Sp1 binding in IPEC-J2 cells. Treatment of the cells with Sp1 inhibitor, mithramycin A, inhibited HDAC1 expression, indicating direct regulation of HDAC1 expression by Sp1. Of the viral proteins that were overexpressed in IPEC-J2 cells, the N protein was found to be present in the nuclei and more inhibitory to transcription. The putative NLS PKKNKSR contributed to its nuclear localization. The N protein interacted with Sp1 and interfered with its binding to the promoter region, thereby inhibiting its transcriptional activity for expression. Our findings reveal a novel mechanism of PEDV evasion of the host responses, offering implications for studying the infection processes of other coronaviruses. The enteric coronavirus porcine epidemic diarrhea virus (PEDV) causes fatal acute intestinal infection in neonatal pigs that rely on innate immune responses. Histone deacetylases (HDACs) play important roles in innate immune regulation. Our study found PEDV suppresses HDAC1 expression via the interaction of its N protein and porcine Sp1, which identified a novel mechanism of PEDV evasion of the host responses to benefit its replication. This study suggests that other coronaviruses, including SARS-CoV and SARS-CoV-2, may also make use of their N proteins to intercept the host immune responses in favor of their infection.
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http://dx.doi.org/10.1128/JVI.00853-21DOI Listing
July 2021

Stress-Induced Progression of Atrioventricular Block in a Patient with Breathlessness.

JAMA Intern Med 2021 Jul 6. Epub 2021 Jul 6.

Department Cardiology, Homerton University Hospital NHS Foundation Trust, London, England.

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http://dx.doi.org/10.1001/jamainternmed.2021.2970DOI Listing
July 2021

Xanthomonas effector XopR hijacks host actin cytoskeleton via complex coacervation.

Nat Commun 2021 07 1;12(1):4064. Epub 2021 Jul 1.

School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.

The intrinsically disordered region (IDR) is a preserved signature of phytobacterial type III effectors (T3Es). The T3E IDR is thought to mediate unfolding during translocation into the host cell and to avoid host defense by sequence diversification. Here, we demonstrate a mechanism of host subversion via the T3E IDR. We report that the Xanthomonas campestris T3E XopR undergoes liquid-liquid phase separation (LLPS) via multivalent IDR-mediated interactions that hijack the Arabidopsis actin cytoskeleton. XopR is gradually translocated into host cells during infection and forms a macromolecular complex with actin-binding proteins at the cell cortex. By tuning the physical-chemical properties of XopR-complex coacervates, XopR progressively manipulates multiple steps of actin assembly, including formin-mediated nucleation, crosslinking of F-actin, and actin depolymerization, which occurs through competition for actin-depolymerizing factor and depends on constituent stoichiometry. Our findings unravel a sophisticated strategy in which bacterial T3E subverts the host actin cytoskeleton via protein complex coacervation.
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http://dx.doi.org/10.1038/s41467-021-24375-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249405PMC
July 2021

High-efficiency charge transfer on SERS-active semiconducting KTiO nanowires enables direct transition of photoinduced electrons to protein redox centers.

Biosens Bioelectron 2021 Jun 19;191:113452. Epub 2021 Jun 19.

Department of Chemistry, Institute for Molecular Science and Fusion Technology, Kangwon National University, Chunchon, 24341, South Korea. Electronic address:

Photoinduced charge transfer (PICT) plays a crucial role in the chemical mechanism of surface-enhanced Raman scattering (SERS), in which small organic molecules are generally used as probes. Herein, semiconducting KTiO nanowires (NWs) are synthesized and are found to exhibit high SERS activity probed by 4-mercaptobenzoic acid (4-MBA). Density functional theory (DFT) calculations reveal high-efficiency CT on the KTiO nanowires. Furthermore, PICT on the KTiO NWs is for the first time evidenced by a redox protein, cytochrome c (Cyt c). Under optimized experimental conditions, the transformation of oxidized Cyt c to its reduced state clearly verifies the electron transfer (ET) from the KTiO nanowire to the protein. The ET mechanism is explored based on energy levels of semiconductors and molecular dynamics simulations, thus revealing the importance of energy level matching and electron tunneling from the semiconductor surface to the redox center. This study indicates a great potential of multiple-layered KTiO NWs in the application of SERS on semiconducting materials and more importantly, it provides a new route for the rational design of protein-semiconductor interfaces for investigating electron transfer processes of redox proteins and biocatalytic reactions.
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http://dx.doi.org/10.1016/j.bios.2021.113452DOI Listing
June 2021

The Anti-Non-Small Cell Lung Cancer Cell Activity by a mTOR Kinase Inhibitor PQR620.

Front Oncol 2021 10;11:669518. Epub 2021 Jun 10.

Department of Thoracic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, China.

In non-small-cell lung carcinoma (NSCLC), aberrant activation of mammalian target of rapamycin (mTOR) contributes to tumorigenesis and cancer progression. PQR620 is a novel and highly-potent mTOR kinase inhibitor. We here tested its potential activity in NSCLC cells. In primary human NSCLC cells and established cell lines (A549 and NCI-H1944), PQR620 inhibited cell growth, proliferation, and cell cycle progression, as well as cell migration and invasion, while inducing significant apoptosis activation. PQR620 disrupted assembles of mTOR complex 1 (mTOR-Raptor) and mTOR complex 2 (mTOR-Rictor-Sin1), and blocked Akt, S6K1, and S6 phosphorylations in NSCLC cells. Restoring Akt-mTOR activation by a constitutively-active Akt1 (S473D) only partially inhibited PQR620-induced cytotoxicity in NSCLC cells. PQR620 was yet cytotoxic in Akt1/2-silenced NSCLC cells, supporting the existence of Akt-mTOR-independent mechanisms. Indeed, PQR620 induced sphingosine kinase 1 (SphK1) inhibition, ceramide production and oxidative stress in primary NSCLC cells. studies demonstrated that daily oral administration of a single dose of PQR620 potently inhibited primary NSCLC xenograft growth in severe combined immune deficient mice. In PQR620-treated xenograft tissues, Akt-mTOR inactivation, apoptosis induction, SphK1 inhibition and oxidative stress were detected. In conclusion, PQR620 exerted potent anti-NSCLC cell activity mTOR-dependent and -independent mechanisms.
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http://dx.doi.org/10.3389/fonc.2021.669518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222575PMC
June 2021

3,3',5-Triiodothyroacetic acid (TRIAC) induces embryonic ζ-globin expression via thyroid hormone receptor α.

J Hematol Oncol 2021 Jun 26;14(1):99. Epub 2021 Jun 26.

Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

The human ζ-globin gene (HBZ) is transcribed in primitive erythroid cells only during the embryonic stages of development. Reactivation of this embryonic globin synthesis would likely alleviate symptoms both in α-thalassemia and sickle-cell disease. However, the molecular mechanisms controlling ζ-globin expression have remained largely undefined. Moreover, the pharmacologic agent capable of inducing ζ-globin production is currently unavailable. Here, we show that TRIAC, a bioactive thyroid hormone metabolite, significantly induced ζ-globin gene expression during zebrafish embryogenesis. The induction of ζ-globin expression by TRIAC was also observed in human K562 erythroleukemia cell line and primary erythroid cells. Thyroid hormone receptor α (THRA) deficiency abolished the ζ-globin-inducing effect of TRIAC. Furthermore, THRA could directly bind to the distal enhancer regulatory element to regulate ζ-globin expression. Our study provides the first evidence that TRIAC acts as a potent inducer of ζ-globin expression, which might serve as a new potential therapeutic option for patients with severe α-thalassemia or sickle-cell disease.
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http://dx.doi.org/10.1186/s13045-021-01108-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235803PMC
June 2021

SOD2 Alleviates Hearing Loss Induced by Noise and Kanamycin in Mitochondrial DNA4834-deficient Rats by Regulating PI3K/MAPK Signaling.

Curr Med Sci 2021 Jun 25;41(3):587-596. Epub 2021 Jun 25.

Department of Otorhinolaryngology, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430016, China.

Superoxide dismutase 2 (SOD2)-mediated gene therapy has significant protective effects against kanamycin-induced hearing loss and hair cell loss in the inner ear, but the underlying mechanisms are still unclear. Herein, an in vivo aging model of mitochondrial DNA (mtDNA)4834 deletion mutation was established using D-galactose, and the effects of noise or kanamycin on inner ear injury was investigated. Rats subjected to mtDNA4834 mutation via D-galactose administration showed hearing loss characterized by the disruption of inner ear structure (abnormal cell morphology, hair cell lysis, and the absence of the organ of Corti), increased SOD2 promoter methylation, and an increase in the degree of apoptosis. Exposure to noise or kanamycin further contributed to the effects of D-galactose. SOD2 overexpression induced by viral injection accordingly counteracted the effects of noise and kanamycin and ameliorated the symptoms of hearing loss, suggesting the critical involvement of SOD2 in preventing deafness and hearing-related conditions. The PI3K and MAPK signaling pathways were also regulated by noise/kanamycin exposure and/or SOD2 overexpression, indicating that they may be involved in the therapeutic effect of SOD2 against age-related hearing loss.
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http://dx.doi.org/10.1007/s11596-021-2376-4DOI Listing
June 2021

ZEB1 directly inhibits GPX4 transcription contributing to ROS accumulation in breast cancer cells.

Breast Cancer Res Treat 2021 Jul 24;188(2):329-342. Epub 2021 Jun 24.

School of Medicine, Nankai University, Tianjin, 300071, China.

Purpose: Prior studies have noted that zinc finger E-box binding homeobox 1 (ZEB1) is a master transcription regulator, affecting the expression of nearly 2000 genes in breast cancer cells, especially in the epithelial-mesenchymal transition (EMT) process. We now tested the role of ZEB1 on the oxidative stress of cancer cells and explored its possible mechanisms.

Methods: Two human breast cancer cell lines MDA-MB-231 and MCF7 were selected for the ROS test, PCR, immunofluorescence, Western blot, chromatin immunoprecipitation assay, luciferase assay, and enzyme assay. Mouse models experiments and bioinformatics analysis were conducted to test the indicated molecules.

Results: We observed ZEB1 could inhibit GPX4 transcription by binding to the E-box motifs and promote breast cancer progression by accumulating intracellular ROS. From the perspective of ROS clearance, Vitamin E enhanced GPX4 function to consume L-glutathione and eliminated excess intracellular ROS.

Conclusions: ZEB1 could not only regulate EMT, but also inhibit GPX4 transcription by binding to the E-box motif. It was important to note that the ZEB1/GPX4 axis had a therapeutic effect on breast cancer metabolism.
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http://dx.doi.org/10.1007/s10549-021-06301-9DOI Listing
July 2021

The predictive prognostic values of , , , , , and in lung cancer.

Ann Transl Med 2021 May;9(10):843

Department of Thoracic Surgery, Affiliated Hospital of Nantong University, Nantong, China.

Background: Lung cancer is one of the most malignant tumors. However, neither the pathogenesis of lung cancer nor the prognosis markers are completely clear. The purpose of this study is to screen the diagnostic or prognostic markers of lung cancer.

Methods: TCGA and GEO datasets were used to analyze the relationship between lung cancer-related genes and lung cancer samples. Common differential genes were screened, and a univariate Cox regression analysis was used to screen survival related genes. A univariable Cox proportional hazards regression analysis was used to verify the genes and construct risk model. The key factors affecting the prognosis of lung cancer were determined by univariate and multivariate regression analyses. The ROC curve, AUC and the survival of each risk gene was analyzed. Finally, the biological functions of high- and low-risk patients were explored by GSEA and an immune-infiltration analysis.

Results: Based on the common differential genes, 13 genes significantly related to lung cancer survival were identified. Eight risk genes (, , , , , , , and ) were screened out. The results showed that risk status may be an independent prognostic factor, and the risk score predicted the prognosis of lung cancer. and are protective genes, while , , and are dangerous genes. These 6 genes can be used as independent lung cancer prognosis markers. The corresponding biological functions of genes expressed in high-risk patients were mostly related to tumor proliferation and inflammatory infiltration. Neutrophil, CD8T, Macrophage M0, Macrophage M1- and mDC-activated cells were high in high-risk status samples.

Conclusions: , , , , , and are important participants in the occurrence and development of lung cancer. High-risk patients display serious inflammatory infiltration. This study not only provides insight into the mechanism of occurrence and development of lung cancer, but also provides potential targets for targeted therapy of lung cancer.
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http://dx.doi.org/10.21037/atm-21-1392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184469PMC
May 2021

Serum- and Glucocorticoid-Inducible Kinase 1 Promotes Alternative Macrophage Polarization and Restrains Inflammation through FoxO1 and STAT3 Signaling.

J Immunol 2021 Jun 23. Epub 2021 Jun 23.

Department of Oral and Craniofacial Molecular Biology, VCU Philips Institute for Oral Health Research, Virginia Commonwealth University, Richmond, VA;

Expression and activity of serum- and glucocorticoid-inducible kinase 1 (SGK1) are associated with many metabolic and inflammatory diseases. In this study, we report that SGK1 promotes alternative macrophage polarization and restrains inflammation in the infectious milieu of the gingiva. Inhibition of SGK1 expression or activity enhances characteristics of classically activated (M1) macrophages by directly activating the transcription of genes encoding iNOS, IL-12P40, TNF-α, and IL-6 and repressing IL-10 at message and protein levels. Moreover, SGK1 inhibition robustly reduces the expression of alternatively activated (M2) macrophage molecular markers, including arginase-1, Ym-1, Fizz1, and Mgl-1. These results were confirmed by multiple gain- and loss-of-function approaches, including small interfering RNA, a plasmid encoding SGK1, and -Cre-mediated gene knockout. Further mechanistic analysis showed that SGK1 deficiency decreases STAT3 but increases FoxO1 expression in macrophages under M2 or M1 macrophage-priming conditions, respectively. Combined with decreased FoxO1 phosphorylation and the subsequent suppressed cytoplasmic translocation observed, SGK1 deficiency robustly enhances FoxO1 activity and drives macrophage to preferential M1 phenotypes. Furthermore, FoxO1 inhibition abrogates M1 phenotypes, and STAT3 overexpression results in a significant increase of M2 phenotypes, indicating that both FoxO1 and STAT3 are involved in SGK1-mediated macrophage polarization. Additionally, SGK1 differentially regulates the expression of M1 and M2 molecular markers, including CD68 and F4/F80 and CD163 and CD206, respectively, and protects against -induced alveolar bone loss in a mouse model. Taken together, these results have demonstrated that SGK1 is critical for macrophage polarization and periodontal bone loss, and for the first time, to our knowledge, we elucidated a bifurcated signaling circuit by which SGK1 promotes alternative, while suppressing inflammatory, macrophage polarization.
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http://dx.doi.org/10.4049/jimmunol.2001455DOI Listing
June 2021

Harnessing the power of antibodies to fight bone metastasis.

Sci Adv 2021 Jun 23;7(26). Epub 2021 Jun 23.

Department of Chemistry, Rice University, 6100 Main Street, Houston, TX 77005, USA.

Antibody-based therapies have proved to be of great value in cancer treatment. Despite the clinical success of these biopharmaceuticals, reaching targets in the bone microenvironment has proved to be difficult due to the relatively low vascularization of bone tissue and the presence of physical barriers. Here, we have used an innovative bone-targeting (BonTarg) technology to generate a first-in-class bone-targeting antibody. Our strategy involves the use of pClick antibody conjugation technology to chemically couple the bone-targeting moiety bisphosphonate to therapeutic antibodies. Bisphosphonate modification of these antibodies results in the delivery of higher conjugate concentrations to the bone metastatic niche, relative to other tissues. In xenograft mice models, this strategy provides enhanced inhibition of bone metastases and multiorgan secondary metastases that arise from bone lesions. Specific delivery of therapeutic antibodies to the bone, therefore, represents a promising strategy for the treatment of bone metastatic cancers and other bone diseases.
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http://dx.doi.org/10.1126/sciadv.abf2051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221630PMC
June 2021

The Arabidopsis circadian clock protein PRR5 interacts with and stimulates ABI5 to modulate abscisic acid signaling during seed germination.

Plant Cell 2021 Jun 21. Epub 2021 Jun 21.

CAS Key Laboratory of Tropical Plant Resources and Sustainable Use, Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences, Kunming, Yunnan 650223, China.

Seed germination and postgerminative growth require the precise coordination of multiple intrinsic and environmental signals. The phytohormone abscisic acid (ABA) suppresses these processes in Arabidopsis thaliana and the circadian clock contributes to the regulation of ABA signaling. However, the molecular mechanism underlying circadian clock-mediated ABA signaling remains largely unknown. Here, we found that the core circadian clock proteins PSEUDO-RESPONSE REGULATOR5 (PRR5) and PRR7 physically associate with ABSCISIC ACID INSENSITIVE5 (ABI5), a crucial transcription factor of ABA signaling. PRR5 and PRR7 positively modulate ABA signaling redundantly during seed germination. Disrupting PRR5 and PRR7 simultaneously rendered germinating seeds hyposensitive to ABA, whereas overexpression of PRR5 enhanced ABA signaling to inhibit seed germination. Consistent with this, the expression of several ABA-responsive genes is upregulated by PRR proteins. Genetic analysis demonstrated that PRR5 promotes ABA signaling mainly dependently on ABI5. Further mechanistic investigation revealed that PRR5 stimulates the transcriptional function of ABI5 without affecting its stability. Collectively, our results indicate that these PRR proteins function synergistically with ABI5 to activate ABA responses during seed germination, thus providing a mechanistic understanding of how ABA signaling and the circadian clock are directly integrated through a transcriptional complex involving ABI5 and central circadian clock components.
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http://dx.doi.org/10.1093/plcell/koab168DOI Listing
June 2021

Tailoring Unsymmetrical-Coordinated Atomic Site in Oxide-Supported Pt Catalysts for Enhanced Surface Activity and Stability.

Small 2021 Jun 21:e2101008. Epub 2021 Jun 21.

Hefei National Laboratory for Physical Sciences at the Microscale, Collaborative Innovation Center of Chemistry for Energy Materials (iChEM), School of Chemistry and Materials Science, and National Synchrotron Radiation Laboratory, University of Science and Technology of China, Hefei, 230026, China.

The catalytic properties of supported metal heterostructures critically depend on the design of metal sites. Although it is well-known that the supports can influence the catalytic activities of metals, precisely regulating the metal-support interactions to achieve highly active and durable catalysts still remain challenging. Here, the authors develop a support effect in the oxide-supported metal monomers (involving Pt, Cu, and Ni) catalysts by means of engineering nitrogen-assisted nanopocket sites. It is found that the nitrogen-permeating process can induce the reconstitution of vacancy interface, resulting in an unsymmetrical atomic arrangement around the vacancy center. The resultant vacancy framework is more beneficial to stabilize Pt monomers and prevent diffusion, which can be further verified by the density functional theory calculations. The final Pt-N/SnO catalysts exhibit superior activity and stability for HCHO response (26.5 to 15 ppm). This higher activity allows the reaction to proceed at a lower operating temperature (100 °C). Incorporated with wireless intelligent-sensing system, the Pt-N/SnO catalysts can further achieve continuous monitoring of HCHO levels and cloud-based terminal data storage.
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http://dx.doi.org/10.1002/smll.202101008DOI Listing
June 2021

Circular RNA AFF4 modulates osteogenic differentiation in BM-MSCs by activating SMAD1/5 pathway through miR-135a-5p/FNDC5/Irisin axis.

Cell Death Dis 2021 Jun 18;12(7):631. Epub 2021 Jun 18.

Department of Orthopedics, The First Affiliated Hospital of University of South China, Hengyang, 421001, Hunan Province, PR China.

Bone marrow-derived mesenchymal stem cells (BM-MSCs), the common progenitor cells of adipocytes and osteoblasts, have been recognized as the key mediator during bone formation. Herein, our study aim to investigate molecular mechanisms underlying circular RNA (circRNA) AFF4 (circ_AFF4)-regulated BM-MSCs osteogenesis. BM-MSCs were characterized by FACS, ARS, and ALP staining. Expression patterns of circ_AFF4, miR-135a-5p, FNDC5/Irisin, SMAD1/5, and osteogenesis markers, including ALP, BMP4, RUNX2, Spp1, and Colla1 were detected by qRT-PCR, western blot, or immunofluorescence staining, respectively. Interactions between circ_AFF4 and miR-135a-5p, FNDC5, and miR-135a-5p were analyzed using web tools including TargetScan, miRanda, and miRDB, and further confirmed by luciferase reporter assay and RNA pull-down. Complex formation between Irisin and Integrin αV was verified by Co-immunoprecipitation. To further verify the functional role of circ_AFF4 in vivo during bone formation, we conducted animal experiments harboring circ_AFF4 knockdown, and born samples were evaluated by immunohistochemistry, hematoxylin and eosin, and Masson staining. Circ_AFF4 was upregulated upon osteogenic differentiation induction in BM-MSCs, and miR-135a-5p expression declined as differentiation proceeds. Circ_AFF4 knockdown significantly inhibited osteogenesis potential in BM-MSCs. Circ_AFF4 stimulated FNDC5/Irisin expression through complementary binding to its downstream target molecule miR-135a-5p. Irisin formed an intermolecular complex with Integrin αV and activated the SMAD1/5 pathway during osteogenic differentiation. Our work revealed that circ_AFF4, acting as a sponge of miR-135a-5p, triggers the promotion of FNDC5/Irisin via activating the SMAD1/5 pathway to induce osteogenic differentiation in BM-MSCs. These findings gained a deeper insight into the circRNA-miRNA regulatory system in the bone marrow microenvironment and may improve our understanding of bone formation-related diseases at physiological and pathological levels.
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http://dx.doi.org/10.1038/s41419-021-03877-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213698PMC
June 2021

Novel Bioactive Glass-Modified Hybrid Composite Resin: Mechanical Properties, Biocompatibility, and Antibacterial and Remineralizing Activity.

Front Bioeng Biotechnol 2021 1;9:661734. Epub 2021 Jun 1.

Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.

Secondary caries seriously limits the lifetime of composite resin. However, integrating all desirable properties (i.e., mechanical, antibacterial, bioactivity, and biocompatibility) into one composite resin is still challenging. Herein, a novel bioactive glass (BAG)-modified hybrid composite resin has been successfully developed to simultaneously achieve excellent mechanical properties, good biocompatibility, and antibacterial and remineralizing capabilities. When the mass fractions of BAG particles were added from 8 to 23 wt %, the original mechanical properties of the composite resin, including flexural strength and compressive strength, were not obviously affected without compromising the degree of conversion. Although the BAG incorporation of mass fractions of 16 wt % to 23 wt % in composite resins reduced cell viability, the viability could be recovered to normal by adjusting the pH value. Moreover, the BAG-modified composite resins that were obtained showed good antibacterial effects against and enhanced remineralizing activity on demineralized dentin surfaces with increasing incorporation of BAG particles. The possible mechanisms for antibacterial and remineralizing activity might be closely related to the release of bioactive ions (Ca, Si), suggesting that its antibacterial and biological properties can be controlled by modulating the amounts of bioactive ions. The capability to balance the mechanical properties, cytotoxicity, antibacterial activity, and bioactivity makes the BAG-modified composite resin a promising prospect for clinical application. Our findings provide insight into better design and intelligent fabrication of bioactive composite resins.
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http://dx.doi.org/10.3389/fbioe.2021.661734DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205519PMC
June 2021

Analysis of Iris volume using swept-source optical coherence tomography in patients with type 2 diabetes mellitus.

Acta Ophthalmol 2021 Jun 16. Epub 2021 Jun 16.

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

Purpose: To evaluate iris volume before and after pupil dilation using swept-source anterior segment optical coherence tomography (SS-ASOCT) and investigate the associated factors of iris volume and iris volume change after pupil dilation in patients with type 2 diabetes mellitus (T2DM).

Methods: A cross-sectional study was conducted in Zhongshan Ophthalmic Center among T2DM registered patients in the community of Guangzhou, China. Anterior chamber volume (ACV), iris volume, anterior chamber depth (ACD), angle opening distance at 500 μm (AOD 500) and pupil diameter were estimated using SS-ASOCT (CASIA; Tomey, Nagoya, Japan). Venous blood was taken for the measurement of glycosylated haemoglobin A1c (HbAlc). All biometric measurements were performed before and after pharmacologic pupil dilation.

Results: A total of 117 subjects were included in the analysis. The mean age (±SD) was 64.96 ± 7.75 years, and 62.4% were females. After pupil dilation, iris volume decreased in all eyes. Shorter duration of diabetes (p = 0.035), longer axial length (p < 0.001) and smaller pupil diameter (p < 0.001) were associated with larger iris volume. The change in iris volume per millimetre change in pupil diameter was 1.35mm /mm. Smaller baseline iris volume (p = 0.002) and higher HbA1c level (p = 0.010) were associated with smaller change in iris volume per millimetre change in pupil diameter, after adjusting for other factors.

Conclusion: Iris volume can be estimated by SS-ASOCT. Diabetic duration was associated with static anatomy of iris volume, while HbA1c level indicated the dynamic response of iris volume. It is likely that diabetic duration and HbA1c level could affect the macroscopic and microscopic composition of the iris in the diabetic population.
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http://dx.doi.org/10.1111/aos.14931DOI Listing
June 2021

Salvage surgery following downstaging of advanced non-small cell lung cancer by targeted therapy.

Thorac Cancer 2021 Jun 15. Epub 2021 Jun 15.

Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Advanced non-small cell lung cancer (NSCLC) accounts for a high proportion of lung cancer cases. Targeted therapy improve the survival in these patients, but acquired drug resistance will inevitably occur. If tumor downstaging is achieved after targeted therapy, could surgical resection before drug resistance improve clinical benefits for patients with advanced NSCLC? Here, we conducted a clinical trial showing that for patients with advanced driver gene mutant NSCLC who did not progress after targeted therapy, salvage surgery (SS) could improve progression-free survival (PFS). Herein, we retrospectively reviewed our former clinical trial and thoracic cancer database in our medical institutions.

Methods: We identified patients with advanced driver gene mutant NSCLC treated with targeted therapy plus SS or targeted therapy alone in our former clinical trial and our thoracic cancer database from July 2016 to July 2019. PFS was compared between the targeted therapy plus SS group and the targeted therapy only group using the log-rank test.

Results: We identified 73 patients with driver gene mutant NSCLC who were treated with targeted therapy and 18 treated with targeted therapy plus SS.Among the 18 patients treated with targeted therapy plus SS, there were no obvious perioperative complications and deaths. Targeted therapy followed by SS resulted in a significantly longer PFS compared with targeted therapy alone (23.4 months VS 12.9 months, p = 0.0004).

Conclusions: Salvage surgery after tumor downstaging is a promising therapeutic strategy for some patients with advanced (stage IIIB-IV) NSCLC and may offer a new therapeutic option for multidisciplinary comprehensive treatment of lung cancer.
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http://dx.doi.org/10.1111/1759-7714.14044DOI Listing
June 2021

Fucoidan reduces lipid accumulation by promoting foam cell autophagy via TFEB.

Carbohydr Polym 2021 Sep 26;268:118247. Epub 2021 May 26.

Marine College, Shandong University, Weihai, Shandong, China. Electronic address:

Atherosclerotic cardiovascular disease became one of the major causes of morbidity and mortality worldwide. As a sulfated polysaccharide with anti-inflammatory and hypolipidemic activities, fucoidan can induce autophagy. We show here that fucoidan reduces lipid accumulation in foam cells, which is one of the causes of atherosclerosis. Further studies show that fucoidan promotes autophagy showed by the expression of p62/SQSTM1 and microtubule-associated protein light chain 3 (LC3) II, which can be blocked by autophagy inhibitors 3-MA and bafilomycin A1. In addition, the expression of transcription factor EB (TFEB), master regulator of autophagy and lysosome function, is upregulated after the treatment with fucoidan. Moreover, the knockout of TFEB with small interfering RNA suppressed the effect of fucoidan. Together, fucoidan reduces lipid accumulation in foam cells by enhancing autophagy through the upregulation of TFEB. In view of the role of foam cells in atherosclerosis, fucoidan can be valuable for the treatment of atherosclerosis.
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http://dx.doi.org/10.1016/j.carbpol.2021.118247DOI Listing
September 2021

The associations of birth outcome differences in twins with prenatal exposure to bisphenol A and its alternatives.

Environ Res 2021 Jun 11;200:111459. Epub 2021 Jun 11.

Department of Occupational and Environmental Health, School of Basic Medicine and Public Health, Jinan University, Guangzhou, Guangdong, PR China. Electronic address:

Background: Bisphenol A (BPA) and its alternatives, including BPF and BPS, exhibit endocrine disruption activities. However, the effects of bisphenols on fetal growth in twins remain unclear.

Objective: To explore the associations of prenatal BPA, BPF, and BPS exposure with birth outcome differences in twins.

Methods: We recruited 289 twin pregnant women who visited the hospital for prenatal examination during the first trimester from 2013 to 2016. Urinary bisphenol levels were determined during the first, second, and third trimesters. The associations of maternal exposure to bisphenols with birth outcome differences in twins were analyzed after stratification by different trimesters. We applied the multiple informant model to estimate trimester-specific associations between urinary bisphenol concentrations and birth outcome differences in twins.

Results: We found low reproducibility (ICC<0.40) for maternal urinary BPA and moderate reproducibility (0.40 < ICC<0.75) for BPF and BPS. Urinary BPA concentrations were positively associated with within-pair twin birth weight difference when comparing the third vs. the first tertile in each of the three trimesters (i.e., 133.06 g, 95% CI: 68.19, 197.94; 144.5 g, 95%CI: 81.82-207.18 g; and 135.04 g, 95%CI: 71.37-198.71 g for the 1st, 2nd, and 3rd trimester, respectively). The effect of urinary BPA concentration on increased birth length difference within-pair twins were also observed across different trimesters (All P for trends < 0.05). Urinary BPA levels were positively associated with the within-pair birth weight and birth length differences across pregnancy trimesters (All of Type 3 P for values < 0.05).

Conclusion: Maternal BPA exposure appeared to influence birth wight and birth length differences in twins. Our results warrant further confirmation.
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http://dx.doi.org/10.1016/j.envres.2021.111459DOI Listing
June 2021