Publications by authors named "Xue Wu"

425 Publications

Super-fast formation of hydrogels based on multi-arm functional polyethylene glycols as endotamponade substitutes.

J Mater Chem B 2021 Oct 26. Epub 2021 Oct 26.

Department of Ophthalmology, West China Hospital of Sichuan University, No. 37 Guoxue Lane, Wuhou District, Chengdu 610041, China.

Polymer-based hydrogels used in the vitreous cavity could lead to an unsatisfactory gel-forming state, uncontrollable swelling, and potential cytotoxicity. Their application can significantly impair the filling effect and cause severe side effects in the surrounding tissues. To address the concerns, a poly(ethylene glycol)-engineered hydrogel capable of fast gel formation (less than 1 min), with an ultralow swelling ratio and no cytotoxicity in the rabbits' eyes, was constructed as a vitreous substitute. The multi-arm polyethylene glycols (PEGs) modified with functional groups (thiol and maleimide) possess high reaction efficiency in the vitreous cavity and present excellent biomimetic characteristics of the natural vitreous humor . After injection with a double syringe a 25-gauge needle in the eyes of rabbits for 6 months, the hydrogel functioned as an artificial vitreous body that could highly promote retinal detachment repair, with excellent biocompatibility and high transparency, and without bio-degradation or ocular complications. Collectively, the fast forming hydrogel could achieve quick and good filling in the vitreous cavity without cytotoxicity, which makes it a promising long-term endotamponade substitute.
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http://dx.doi.org/10.1039/d1tb01825fDOI Listing
October 2021

Residents' subjective mental workload during computerized prescription entry.

Inform Health Soc Care 2021 Oct 21:1-12. Epub 2021 Oct 21.

School of Nursing, Peking University, Beijing, P.R. China.

To examine residents' subjective mental workload when they enter prescriptions in a computerized physician order entry (CPOE) system. Twenty-two residents completed six prescribing tasks in which two factors were manipulated: numerical input method and level of urgency. Data on demographic characteristics, familiarity with CPOE, and pretest performance were collected. The subjective mental workload was measured by the National Aeronautics and Space Administration-Task Load Index (NASA-TLX). Temporal demand (Mean = 34.48) contributed most to residents' workload on the CPOE task, followed by Performance (Mean = 29.23). No significant associations were found between workload and demographic characteristics, CPOE familiarity, or pretest CPOE performance ('s > .05). A 3 × 2 repeated-measures ANOVA yielded main effects of numerical input method [ (2, 19) = 88.358, < .001, η = .900] and level of urgency [ (1, 21) = 169.654, < .001, η = .890], and interaction of input method and urgency [ (2, 20) = 87.427, < .001, η = .900]. Residents' major sources of workload during the CPOE prescription were temporal demand and performance. Prescriptions entered by the row of numbers exhibited the highest workload. Workload increased with higher level of urgency. It is necessary to emphasize the negative impact of subjective workload, especially in prescription task under urgent situation. Further researches focus on medical staff's workload are encouraged to ensure patient safety.
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http://dx.doi.org/10.1080/17538157.2021.1990932DOI Listing
October 2021

The development of behavioral sensitization induced by a single morphine exposure in adult zebrafish (Danio rerio).

Prog Neuropsychopharmacol Biol Psychiatry 2021 Oct 15;113:110456. Epub 2021 Oct 15.

State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Macau, China. Electronic address:

Background: Accumulating evidence suggest that behavioral sensitization is involved in the process of drug addiction. Zebrafish are sensitive to a variety of addictive drugs and are thus suitable for the study of behavioral sensitization. However, in contrast to mature rodent models of behavioral sensitization, how this phenomenon manifests in aquatic organisms, especially zebrafish, is largely unknown. In this study, we developed a morphine-induced behavioral sensitization adult zebrafish model and performed a preliminary investigation of the underlying mechanisms.

Methods: Behavioral sensitization was established in zebrafish by observing their behavior after treatment and challenge with morphine. The effect of morphine was evaluated by a behavioral locomotor test. Different doses of morphine and withdrawal times were used to evaluate the establishment of the behavioral sensitization model.

Results: Hyperlocomotion was induced after administration of morphine in adult zebrafish. After withdrawing the drug for a period, challenge with low-dose morphine evoked behavioral sensitization in zebrafish acutely pre-treated with morphine. Low-dose morphine failed to induce behavioral sensitization in zebrafish if the withdrawal time was less than 5 days or more than 7 days. Morphine induced behavioral sensitization in zebrafish may involve dopaminergic, glutamatergic and opioid systems.

Conclusion: A single low-dose of morphine could induce behavioral sensitization in zebrafish acutely pre-treated with morphine, and this phenomenon was highly correlated with drug dose and withdrawal time. These findings suggest that zebrafish is a suitable model for the study of behavioral sensitization.
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http://dx.doi.org/10.1016/j.pnpbp.2021.110456DOI Listing
October 2021

Development of a Plasma Biomarker Diagnostic Model Incorporating Ultrasensitive Digital Immunoassay as a Screening Strategy for Alzheimer Disease in a Chinese Population.

Clin Chem 2021 Oct 18. Epub 2021 Oct 18.

Institute of Neurology, Huashan Hospital, Fudan University, Shanghai, China.

Background: The ultrasensitive detection of blood-based biomarkers such as amyloid β (Aβ), tau, and neurofilament light (NFL) has drawn much attention in Alzheimer disease (AD) diagnosis. However, few studies have been conducted in the Chinese population. This study aimed to evaluate the ability of plasma biomarker diagnostic models for AD in the Chinese population based on a novel digital immunoassay technology.

Methods: 159 patients with AD, 148 patients with amnestic mild cognitive impairment (aMCI), and 121 cognitively normal control participants were recruited from 2 cohorts. The concentrations of plasma Aβ42, Aβ40, Aβ42/Aβ40, total tau (t-tau), phosphorylated tau 181 (p-tau 181), and NFL were quantified using an ultrasensitive single molecule array (Simoa) platform. Comprehensive and simplified diagnostic models were established based on the plasma biomarker profile and clinical characteristics.

Results: Among all blood biomarkers, p-tau181 had the greatest potential for identifying patients with cognitive impairment. The simplified diagnostic model, which combined plasma p-tau181, Aβ42, and clinical features, achieved 93.3% area under the curve (AUC), 78.6% sensitivity, and 94.2% specificity for distinguishing AD from control participants, indicating a diagnostic ability approaching that of the comprehensive diagnostic model including 5 plasma biomarkers and clinical characteristics (95.1% AUC, 85.5% sensitivity, 94.2% specificity). Moreover, the simplified model reached 95.9% AUC and 94.0% AUC for early- and late-onset AD/control participants, respectively.

Conclusions: We established AD diagnostic models using plasma biomarkers for Chinese participants. These findings suggest the simplified diagnostic model provides an accessible and practical way for large-scale screening in the clinic and community, especially in developing countries.
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http://dx.doi.org/10.1093/clinchem/hvab192DOI Listing
October 2021

Genetic Profiling of Cell-Free DNA From Pleural Effusion in Advanced Lung Cancer as a Surrogate for Tumor Tissue and Revealed Additional Clinical Actionable Targets.

Clin Lung Cancer 2021 Sep 20. Epub 2021 Sep 20.

Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China; School of Medicine, South China University of Technology, Guangzhou, China. Electronic address:

Background: Pleural effusion (PE) has been one of the promising sources of liquid biopsy in advanced lung cancer patients. However, its clinical utility is not widely accepted due to the lack of full estimation of its potential versus routine clinical samples.

Method: A total of 164 advanced lung cancer patients were enrolled with 164 matched tumor tissue and PE-cfDNA, 153 accompanied plasma and 63 PE-sDNA.

Result: PE-cfDNA displayed significantly higher median mutant allele frequency and an overall mutation concordance rate of 65% to tissue, which was higher than PE-sDNA (43%) and plasma-cfDNA (43%). The discrepancies between PE-cfDNA and tumor tissue were high in several genes, including SMARCA4, PIK3CA, ERBB2, KM T2A, ALK and NF1. For clinically actionable mutations, the concordance rate between PE-cfDNA and tumor tissue is 87%. Eleven patients were identified with actionable mutations in PE-cfDNA and four patients benefited from PE-cfDNA-guided targeted. Meanwhile, PE-cfDNA recapitulated mutations of diverse tissue origins and provided more mutational information under the circumstance that tumor tissue or tumor tissue of different origins were unavailable. The combination of tumor tissue and PE-cfDNA profiling increased positive detection rates of patients compared to tumor tissue alone. Our finding highlighted the importance of PE-cfDNA in the optimal selection of patients for targeted therapy.

Conclusion: The PE-cfDNA-based liquid biopsy displays better performance in the characterization of gene alterations than PE-sDNA and plasma-cfDNA. PE-cfDNA together with tumor tissue profiling optimizes comprehensively genomic profiling of lung cancer patients, which might be important for selecting patients for better treatment management.
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http://dx.doi.org/10.1016/j.cllc.2021.09.002DOI Listing
September 2021

Co-Mutational Features and NGS-Calibrated Immunohistochemistry Threshold in Gastric Cancer.

Onco Targets Ther 2021 1;14:4967-4978. Epub 2021 Oct 1.

Department of Pathology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan, People's Republic of China.

Purpose: is the most frequently mutated gene in gastric cancer and it can be potentially used for gastric cancer diagnosis and screening. However, standardized clinical approaches that could accurately and cost-effectively detect mutations in gastric cancer are largely lagged behind.

Patients And Methods: We conducted next-generation sequencing (NGS) analysis of 425 cancer-related genes in 42 gastric cancer patients in our cohort. A 1313-patient cohort derived from the cBioPortal database was used for validation. We performed immunohistochemistry (IHC) staining with four commonly used p53 antibodies, and the NGS results were used as the gold standard to optimize the IHC threshold for each antibody.

Results: By NGS analysis, we found that around 80% of gastric cancer patients in our cohort harbored alterations. Genetic alterations of / or were mostly exclusive with mutations, so were the MSI status or low grade of tumors. These results were further validated using the data from cBioPortal. We then used the NGS-derived status to optimize four commonly used IHC antibodies for detecting mutations. We showed that all antibodies could achieve more than 93% accuracy when proper IHC positivity thresholds were used, especially for the SP5 antibody that could reach 100% sensitivity and specificity with the 20% threshold.

Conclusion: Our results indicated that exclusivity between and mutations could be potentially used as a cost-effective way to predict status. Also, setting proper IHC thresholds for each specific antibody is critical to accurately detect mutations and facilitate disease diagnosis.
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http://dx.doi.org/10.2147/OTT.S321949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8493115PMC
October 2021

Hypoxia signaling: Challenges and opportunities for cancer therapy.

Semin Cancer Biol 2021 Oct 7. Epub 2021 Oct 7.

School of Medicine, Cardiff University, Cardiff, UK.

Hypoxia is arguably the first recognized cancer microenvironment hallmark and affects virtually all cellular populations present in tumors. During the past decades the complex adaptive cellular responses to oxygen deprivation have been largely elucidated, raising hope for new anti cancer agents. Despite undeniable preclinical progress, therapeutic targeting of tumor hypoxia is yet to transition from bench to bedside. This review focuses on new pharmacological agents that exploit tumor hypoxia or interfere with hypoxia signaling and discusses strategies to maximize their therapeutic impact.
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http://dx.doi.org/10.1016/j.semcancer.2021.10.002DOI Listing
October 2021

Genomic Profiling Reveals the Molecular Landscape of Gastrointestinal Tract Cancers in Chinese Patients.

Front Genet 2021 14;12:608742. Epub 2021 Sep 14.

Jiangsu Provincial Cancer Hospital Affiliated to Nanjing Medical University, Nanjing, China.

Gastrointestinal tract cancers have high incidence and mortality in China, but their molecular characteristics have not been fully investigated. We sequenced 432 tumor samples from the colorectum, stomach, pancreas, gallbladder, and biliary tract to investigate cancer-related mutations and detail the landscape of microsatellite instability (MSI), tumor mutation burden (TMB), and chromosomal instability (CIN). We observed the highest TMB in colorectal and gastric cancers and the lowest TMB in gastrointestinal stromal tumors (GISTs). Twenty-four hyper-mutated tumors were identified only in colorectal and gastric cancers, with a significant enrichment of mutations in the polymerase genes (, , and ) and mismatch repair (MMR) genes. Additionally, CIN preferentially occurred in colorectal and gastric cancers, while pancreatic, gallbladder, and biliary duct cancers had a much lower CIN. High CIN was correlated with a higher prevalence of malfunctions in chromosome segregation and cell cycle genes, including the copy number loss of , , , and , and the copy number gain of , , , and . In addition, mutations were more abundant in high-CIN tumors, while mutations were more frequent in low-CIN tumors. In colorectal and gastric cancers, tumors with MSI demonstrated much fewer copy number changes than microsatellite stable (MSS) tumors. In colorectal and gastric cancers, the molecular characteristics of tumors revealed the mutational diversity between the different anatomical origins of tumors. This study provides novel insights into the molecular landscape of Chinese gastrointestinal cancers and the genetic differences between tumor locations, which could be useful for future clinical patient stratification and targeted interventions.
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http://dx.doi.org/10.3389/fgene.2021.608742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8478156PMC
September 2021

The effect of human GRIN1 gene 5' functional region on gene expression regulation in vitro.

Gene 2021 Sep 27;808:145973. Epub 2021 Sep 27.

School of Forensic Medicine, China Medical University, Shenyang 110122, China. Electronic address:

Introduction: Abnormal expression of ionotropic glutamate receptor NMDA type subunit 1, the key subunit of the NMDA receptor, may be related to many neuropsychiatric disorders. In this study, we explored the functional sequence of the 5' regulatory region of the human GRIN1 gene and discussed the transcription factors that may regulate gene expression.

Materials And Methods: Twelve recombinant pGL3 vectors with gradually truncated fragment lengths were constructed, transfected into HEK-293, U87, and SK-N-SH cell lines, and analyzed through the luciferase reporter gene assay. JASPAR database is used to predict transcription factors.

Results: In SK-N-SH and U87 cell lines, regions from -337 to -159 bp, -704 to -556 bp inhibited gene expression, while -556 to -337 bp upregulated gene expression. In HEK-293 and U87 cell lines, the expression of fragment -1703 to + 188 bp was significantly increased compared to adjacent fragments -1539 to + 188 bp and -1843 to + 188 bp. The protein expressions of fragments -2162 to + 188 bp and -2025 to + 188 bp, -1539 to + 188 bp and -1215 to + 188 bp, -1215 to + 188 bp and -1066 to + 188 bp were significantly different in HEK-293 and SK-N-SH cells. According to the predictions of the JASPAR database, the transcription factors REST, EGR1, and CREB1/HIC2 may bind the DNA sequences of GRIN1 gene from the -337 to -159, -556 to -337, and -704 to -556, respectively. In addition, zinc finger transcription factors may regulate the expression of other differentially expressed fragments.

Conclusions: Abnormal transcription regulation in the proximal promoter region of GRIN1 (-704 to + 188 bp) may be involved in the course of neuropsychiatric diseases.
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http://dx.doi.org/10.1016/j.gene.2021.145973DOI Listing
September 2021

Superfast and Water-Insensitive Polymerization on α-Amino Acid N-Carboxyanhydrides to Prepare Polypeptides using Tetraalkylammonium carboxylates as the Initiator.

Angew Chem Int Ed Engl 2021 Sep 26. Epub 2021 Sep 26.

East China University of Science and Technology, Materials Science and Engineering, 130 Meilong Road, 200237, Shanghai, CHINA.

Proteins and peptides have diverse biological functions and applications, however, their efficient chemical synthesis is still challenging. We design the tetraalkylammonium carboxylate-initiated superfast polymerization on α-amino acid N -carboxyanhydrides (NCA) for efficient synthesis of polypeptides. Carboxylates, as a new class of initiator for NCA polymerization, can initiate the superfast NCA polymerization without the need of extra catalyst and the polymerization can be operated in open vessels at ambient condition without the use of glove box. Tetraalkylammonium carboxylate-initiated polymerization on NCA easily affords block copolymers with at least 15 blocks. Moreover, this method avoids tedious purification steps and enables direct polymerization on crude NCAs in aqueous environments to prepare polypeptides and one-pot synthesis of polypeptide nanoparticles. These advantages and the mild polymerization condition of tetraalkylammonium carboxylate-initiated NCA polymerization imply its great potential in functional exploration and application of polypeptides.
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http://dx.doi.org/10.1002/anie.202103540DOI Listing
September 2021

Baicalin attenuates blood-spinal cord barrier disruption and apoptosis through PI3K/Akt signaling pathway after spinal cord injury.

Neural Regen Res 2022 May;17(5):1080-1087

College of Pharmacy, Shaanxi University of Chinese Medicine; Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, College of Life Sciences, Shaanxi Normal University; Translational Medicine Center, Hong Hui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.

Baicalin is a natural active ingredient isolated from Scutellariae Radix that can cross the blood-brain barrier and exhibits neuroprotective effects on multiple central nervous system diseases. However, the mechanism behind the neuroprotective effects remains unclear. In this study, rat models of spinal cord injury were established using a modified Allen's impact method and then treated with intraperitoneal injection of Baicalin. The results revealed that Baicalin greatly increased the Basso, Beattie, Bresnahan Locomotor Rating Scale score, reduced blood-spinal cord barrier permeability, decreased the expression of Bax, Caspase-3, and nuclear factor κB, increased the expression of Bcl-2, and reduced neuronal apoptosis and pathological spinal cord injury. SH-SY5Y cell models of excitotoxicity were established by application of 10 mM glutamate for 12 hours and then treated with 40 µM Baicalin for 48 hours to investigate the mechanism of action of Baicalin. The results showed that Baicalin reversed tight junction protein expression tendencies (occludin and ZO-1) and apoptosis-related protein expression (Bax, Bcl-2, Caspase-3, and nuclear factor-κB), and also led to up-regulation of PI3K and Akt phosphorylation. These effects on Bax, Bcl-2, and Caspase-3 were blocked by pretreatment with the PI3K inhibitor LY294002. These findings suggest that Baicalin can inhibit blood-spinal cord barrier permeability after spinal cord injury and reduce neuronal apoptosis, possibly by activating the PI3K/Akt signaling pathway. This study was approved by Animal Ethics Committee of Xi'an Jiaotong University on March 6, 2014.
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http://dx.doi.org/10.4103/1673-5374.324857DOI Listing
May 2022

Genomic characterization and outcome evaluation of kinome fusions in lung cancer revealed novel druggable fusions.

NPJ Precis Oncol 2021 Sep 10;5(1):81. Epub 2021 Sep 10.

Bone Metastasis Service, Department of Orthopaedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

Kinase fusions represent an important type of somatic alterations that promote oncogenesis and serve as diagnostic markers in lung cancer. We aimed to identify the landscape of clinically relevant kinase fusions in Chinese lung cancer and to explore rare kinase rearrangements; thus, providing valuable evidence for therapeutic decision making. We performed genomic profiling of 425 cancer-relevant genes from tumor/plasma biopsies from a total of 17,442 Chinese lung cancer patients using next generation sequencing (NGS). Patients' clinical characteristics and treatment histories were retrospectively studied. A total of 1162 patients (6.66%; 1162/17,442) were identified as having kinase fusions, including 906 adenocarcinomas (ADCs) and 35 squamous cell carcinomas (SCCs). In ADC, 170 unique gene fusion pairs were observed, including rare kinase fusions, SLC12A2-ROS1, NCOA4-RET, and ANK3-RET. As for SCC, 15 unique gene fusions were identified, among which the most frequent were EML4-ALK and FGFR3-TACC3. Analyses of oncogenic mutations revealed a dual role for the gene fusions, CCDC6-RET and FGFR3-TACC3, in driving oncogenesis or serving as acquired resistance mechanisms to kinase inhibitors. In addition, our real-world evidence showed that patients with recurrent kinase fusions with low frequency (two occurrences) could benefit from treatment with kinase inhibitors' off-label use. Notably, patients with stage IV ADC who had novel RORB-ALK or AFF2-RET fusions, but no other known oncogenic driver mutations, demonstrated favorable clinical outcomes on tyrosine kinase inhibitors. Our data provide a comprehensive overview of the landscape of oncogenic kinase fusions in lung cancer, which assist in recognizing potentially druggable fusions that can be translated into therapeutic applications.
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http://dx.doi.org/10.1038/s41698-021-00221-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433182PMC
September 2021

The Roles of CCR9/CCL25 in Inflammation and Inflammation-Associated Diseases.

Front Cell Dev Biol 2021 19;9:686548. Epub 2021 Aug 19.

Department of Paediatrics, Shenmu Hospital, School of Life Sciences and Medicine, Northwest University, Shenmu, China.

Chemokine is a structure-related protein with a relatively small molecular weight, which can target cells to chemotaxis and promote inflammatory response. Inflammation plays an important role in aging. C-C chemokine receptor 9 (CCR9) and its ligand C-C chemokine ligand 25 (CCL25) are involved in the regulating the occurrence and development of various diseases, which has become a research hotspot. Early research analysis of CCR9-deficient mouse models also confirmed various physiological functions of this chemokine in inflammatory responses. Moreover, CCR9/CCL25 has been shown to play an important role in a variety of inflammation-related diseases, such as cardiovascular disease (CVD), rheumatoid arthritis, hepatitis, inflammatory bowel disease, asthma, etc. Therefore, the purpose of this review gives an overview of the recent advances in understanding the roles of CCR9/CCL25 in inflammation and inflammation-associated diseases, which will contribute to the design of future experimental studies on the potential of CCR9/CCL25 and advance the research of CCR9/CCL25 as pharmacological inflammatory targets.
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http://dx.doi.org/10.3389/fcell.2021.686548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416662PMC
August 2021

Long-term ketamine administration induces bladder damage and upregulates autophagy-associated proteins in bladder smooth muscle tissue.

Environ Toxicol 2021 Sep 6. Epub 2021 Sep 6.

School of Forensic Medicine, China Medical University, Shenyang, China.

Long-term ketamine abuse can cause significant lower urinary tract symptoms in humans, termed ketamine-associated cystitis (KC). Here, we established a model of long-term (6 months) ketamine administration in wild-type (C57BL/6) mice. We elucidated the pathological effects of ketamine in the bladder and investigated changes in autophagy-associated protein expression (i.e., LC3, Beclin-1, and P62) and inflammatory cytokines (i.e., IL-6 and IL-1β) in the bladder smooth muscle tissue. Long-term ketamine administration reduced the number of layers in the bladder mucosal epithelial cells (4-5 layers in the saline group vs. 2-3 layers in the ketamine groups), but increased the number of mast cells and collagen fibers. LC3-II/LC3-I, Beclin-1, IL-6, and IL-1β protein expression in the bladder smooth muscle tissues of ketamine-treated mice was significantly increased. The mRNA and protein levels of P62 in the Ket-60 mg/kg group were also significantly increased, but not the Ket-30 mg/kg group. Our results reveal that long-term ketamine administration can cause cystitis-like pathological changes in mice, and the disordered autophagy in the bladder tissue may be involved in the persistent bladder damage following long-term administration of ketamine at 60 mg/kg.
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http://dx.doi.org/10.1002/tox.23365DOI Listing
September 2021

Additive effects of variants of unknown significance in replication repair-associated DNA polymerase genes on mutational burden and prognosis across diverse cancers.

J Immunother Cancer 2021 Sep;9(9)

Institute of Cancer and Basic Medicine (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, China

Background: Defects in replication repair-associated DNA polymerases often manifest an ultra-high tumor mutational burden (TMB), which is associated with higher probabilities of response to immunotherapies. The functional and clinical implications of different polymerase variants remain unclear.

Methods: Targeted next-generation sequencing using a 425-cancer gene panel, which covers all exonic regions of three polymerase genes (, , and ), was conducted in a cohort of 12,266 patients across 16 different tumor types from January 2017 to January 2019. Prognostication of variant-positive patients was performed using a cohort of 4679 patients from the The Cancer Genome Atlas (TCGA) datasets.

Results: The overall prevalence of somatic and germline polymerase variants was 4.2% (95% CI 3.8% to 4.5%) and 0.7% (95% CI 0.5% to 0.8%), respectively, with highest frequencies in endometrial, urinary, prostate, and colorectal cancers (CRCs). While most germline polymerase variants showed no clear functional consequences, we identified a candidate p.T466A affecting the exonuclease domain of POLE, which might be underlying the early onset in a case with childhood CRC. Low frequencies of known hot-spot somatic mutations in were detected and were associated with younger age, the male sex, and microsatellite stability. In both the panel and TCGA cohorts, drivers exhibited high frequencies of alterations in genes in the DNA damage and repair (DDR) pathways, including , , , and . Variants of unknown significance (VUS) of different polymerase domains showed variable penetrance with those in the exonuclease domain of and displaying high TMB. VUS in genes exhibited an additive effect as carriers of multiple VUS had exponentially increased TMB and prolonged overall survival. Similar to cases with driver mutations, the TMB-high VUS samples showed DDR pathway involvement and polymerase hypermutation signatures. Combinatorial analysis of and DDR pathway status further supported the potential additive effects of VUS and DDR pathway genes and revealed distinct prognostic subclasses that were independent of cancer type and TMB.

Conclusions: Our results demonstrate the pathogenicity and additive prognostic value of VUS and DDR pathway gene alterations and suggest that genetic testing may be warranted in patients with diverse solid tumors.
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http://dx.doi.org/10.1136/jitc-2021-002336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8420654PMC
September 2021

Utility of ctDNA in predicting response to neoadjuvant chemoradiotherapy and prognosis assessment in locally advanced rectal cancer: A prospective cohort study.

PLoS Med 2021 Aug 31;18(8):e1003741. Epub 2021 Aug 31.

Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.

Background: For locally advanced rectal cancer (LARC) patients who receive neoadjuvant chemoradiotherapy (nCRT), there are no reliable indicators to accurately predict pathological complete response (pCR) before surgery. For patients with clinical complete response (cCR), a "Watch and Wait" (W&W) approach can be adopted to improve quality of life. However, W&W approach may increase the recurrence risk in patients who are judged to be cCR but have minimal residual disease (MRD). Magnetic resonance imaging (MRI) is a major tool to evaluate response to nCRT; however, its ability to predict pCR needs to be improved. In this prospective cohort study, we explored the value of circulating tumor DNA (ctDNA) in combination with MRI in the prediction of pCR before surgery and investigated the utility of ctDNA in risk stratification and prognostic prediction for patients undergoing nCRT and total mesorectal excision (TME).

Methods And Findings: We recruited 119 Chinese LARC patients (cT3-4/N0-2/M0; median age of 57; 85 males) who were treated with nCRT plus TME at Fudan University Shanghai Cancer Center (China) from February 7, 2016 to October 31, 2017. Plasma samples at baseline, during nCRT, and after surgery were collected. A total of 531 plasma samples were collected and subjected to deep targeted panel sequencing of 422 cancer-related genes. The association among ctDNA status, treatment response, and prognosis was analyzed. The performance of ctDNA alone, MRI alone, and combining ctDNA with MRI was evaluated for their ability to predict pCR/non-pCR. Ranging from complete tumor regression (pathological tumor regression grade 0; pTRG0) to poor regression (pTRG3), the ctDNA clearance rate during nCRT showed a significant decreasing trend (95.7%, 77.8%, 71.1%, and 66.7% in pTRG 0, 1, 2, and 3 groups, respectively, P = 0.008), while the detection rate of acquired mutations in ctDNA showed an increasing trend (3.8%, 8.3%, 19.2%, and 23.1% in pTRG 0, 1, 2, and 3 groups, respectively, P = 0.02). Univariable logistic regression showed that ctDNA clearance was associated with a low probability of non-pCR (odds ratio = 0.11, 95% confidence interval [95% CI] = 0.01 to 0.6, P = 0.04). A risk score predictive model, which incorporated both ctDNA (i.e., features of baseline ctDNA, ctDNA clearance, and acquired mutation status) and MRI tumor regression grade (mrTRG), was developed and demonstrated improved performance in predicting pCR/non-pCR (area under the curve [AUC] = 0.886, 95% CI = 0.810 to 0.962) compared with models derived from only ctDNA (AUC = 0.818, 95% CI = 0.725 to 0.912) or only mrTRG (AUC = 0.729, 95% CI = 0.641 to 0.816). The detection of potential colorectal cancer (CRC) driver genes in ctDNA after nCRT indicated a significantly worse recurrence-free survival (RFS) (hazard ratio [HR] = 9.29, 95% CI = 3.74 to 23.10, P < 0.001). Patients with detectable driver mutations and positive high-risk feature (HR_feature) after surgery had the highest recurrence risk (HR = 90.29, 95% CI = 17.01 to 479.26, P < 0.001). Limitations include relatively small sample size, lack of independent external validation, no serial ctDNA testing after surgery, and a relatively short follow-up period.

Conclusions: The model combining ctDNA and MRI improved the predictive performance compared with the models derived from individual information, and combining ctDNA with HR_feature can stratify patients with a high risk of recurrence. Therefore, ctDNA can supplement MRI to better predict nCRT response, and it could potentially help patient selection for nonoperative management and guide the treatment strategy for those with different recurrence risks.
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http://dx.doi.org/10.1371/journal.pmed.1003741DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8407540PMC
August 2021

A comprehensive study of the genotoxic and anti-genotoxic effects of homocysteine in HUVECs and mouse bone marrow cells.

Food Chem Toxicol 2021 Oct 18;156:112518. Epub 2021 Aug 18.

School of Life Sciences, The Engineering Research Center of Sustainable Development and Utilization of Biomass Energy, Yunnan Normal University, Kunming, Yunnan, 650500, China; Yunnan Environmental Mutagen Society, Kunming, Yunnan, 650500, China. Electronic address:

Elevated Homocysteine (Hcy) is associated with increased risk of vascular disease, but whether it induces genotoxicity to vascular endothelial cells remains unknown. Here, we conducted a comprehensive study of the genotoxicity, and unexpected anti-genotoxicity, of Hcy by cytokinesis-blocked micronucleus assay in HUVECs and erythrocyte micronucleus test in mouse bone marrow cells. Our experiments led to several important findings. First, while supraphysiological Hcy (SP-Hcy) exhibited remarkable genotoxicity, physiologically-relevant Hcy (PR-Hcy) reduced the basal genotoxicity. Second, among the metabolites of Hcy, cysteine phenocopied the anti-genotoxicity of PR-Hcy and, methionine, S-adenosylhomocysteine and HS phenocopied the genotoxicity of SP-Hcy. Third, the genotoxicity of SP-Hcy was mitigated by vitamin B, Fe and Cu, but was exacerbated by N-acetylcysteine. Fourth, under pre-, co- or post-treatment protocol, both SP-Hcy and PR-Hcy attenuated the genotoxicity of cisplatin, mitomycin-C, nocodazole or deoxycholate. Finally, 100 and 250 mg/kg Hcy ameliorated cisplatin-induced genotoxicity in bone marrow cells of CF-1 and Kunming mice. Our results suggest that genotoxicity may be one mechanism through which Hcy confers an increased risk for vascular disease, but more importantly, they challenge the long-standing paradigm that Hcy is always harmful to human health. Our study calls for a more systematic effort in understanding the molecular mechanisms underlying the anti-genotoxicity of Hcy.
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http://dx.doi.org/10.1016/j.fct.2021.112518DOI Listing
October 2021

Photoinduced Copper-Catalyzed Asymmetric Three-Component Coupling of 1,3-Dienes: An Alternative to Kharasch-Sosnovsky Reaction.

Angew Chem Int Ed Engl 2021 10 9;60(42):22956-22962. Epub 2021 Sep 9.

CCNU-uOttawa Joint Research Centre, Key Laboratory of Pesticides & Chemical Biology Ministry of Education, College of Chemistry, Central China Normal University, 152 Luoyu Road, Wuhan, Hubei, 430079, China.

Kharasch-Sosnovsky reaction is one of the most powerful methods for allylic oxidation of alkenes. However, the inherent radical mechanism and use of peroxides as both oxidants and oxygen nucleophiles render dearth of universal catalytic systems for highly enantioselective variants and limited scope. Herein, an alternative to the asymmetric Kharasch-Sosnovsky reaction that utilized a chiral copper catalyst and purple-LED irradiation to enable the three-component coupling of 1,3-dienes, oxime esters, and carboxylic acids is reported. This protocol features mild conditions, remarkable scope and functional group tolerance as evidenced by >80 examples and utility in the late-stage modification of pharmaceuticals and natural products. Detailed mechanistic studies provide evidences for the radical-based reaction pathway.
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http://dx.doi.org/10.1002/anie.202110084DOI Listing
October 2021

WEE1 inhibitor and ataxia telangiectasia and RAD3-related inhibitor trigger stimulator of interferon gene-dependent immune response and enhance tumor treatment efficacy through programmed death-ligand 1 blockade.

Cancer Sci 2021 Aug 11. Epub 2021 Aug 11.

Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

WEE1 plays an important role in the regulation of cell cycle G2/M checkpoints and DNA damage response (DDR). Inhibition of WEE1 can increase the instability of the genome and have anti-tumor effects in some solid tumors. However, it has certain limitations for multiple cancer cells from different lineages. Therefore, we consider the use of synthetic lethal interactions to enhance the therapeutic effect. Our experiments proved that WEE1 inhibitor (WEE1i) can activate the ataxia telangiectasia and RAD3-related (ATR) pathway and that blockage of ATR dramatically sensitized the WEE1i-induced cell death. The tumor-selective synthetic lethality between bioavailable WEE1 and ATR inhibitors led to tumor remission in vivo. Mechanistically, the combination promoted the accumulation of cytosolic double-strand DNA, which subsequently activated the stimulator of the interferon gene (STING) pathway and induced the production of type I interferon and CD8+ T cells, thereby inducing anti-tumor immunity. Furthermore, our study found that immune checkpoint programmed death-ligand 1 is upregulated by the combination therapy, and blocking PD-L1 further enhances the effect of the combination therapy. In summary, as an immunomodulator, the combination of WEE1i with ATR inhibitor (ATRi) and immune checkpoint blockers provides a potential new approach for cancer treatment.
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http://dx.doi.org/10.1111/cas.15108DOI Listing
August 2021

Genomic landscape and evolution of arm aneuploidy in lung adenocarcinoma.

Neoplasia 2021 09 21;23(9):870-878. Epub 2021 Jul 21.

Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. Electronic address:

For lung adenocarcinoma, arm aneuploidy landscape among primary and metastatic sites, and among different driver and frequently mutated gene groups have not been previously studied. We collected the largest cohort of LUAD patients (n=3533) to date and analyzed the profiles of chromosome arm aneuploidy (CAA), and its association with different metastatic sites and mutated gene groups. Our results showed distant metastasis (bone, brain, liver) were characterized by high CAA burden and biased towards arm losses compared to regional metastasis (pleura, chest) and primary tumors. Moreover, EGFR, MET, PIK3CA, PKHD1 and RB1 mutant groups were found to have high CAA burden, while those with BRAF, ERBB2 and KRAS mutations belonged to the low CAA burden group. Comparing EGFR L858R and EGFR 19del mutants, distinct CAA co-occurrences were observed. Network-based stratification with population based genomic evolution analysis revealed two distinct subtypes of LUAD with different CAA signatures and unique CAA order of acquisition. In summary, our study presented a comprehensive characterization of arm aneuploidy landscape and evolutionary trajectories in lung adenocarcinoma, which could provide basis for both biological and clinical investigations in the future.
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http://dx.doi.org/10.1016/j.neo.2021.06.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322129PMC
September 2021

Pixel-wise body composition prediction with a multi-task conditional generative adversarial network.

J Biomed Inform 2021 08 18;120:103866. Epub 2021 Jul 18.

Department of Computer Science, The George Washington University, USA.

The analysis of human body composition plays a critical role in health management and disease prevention. However, current medical technologies to accurately assess body composition such as dual energy X-ray absorptiometry, computed tomography, and magnetic resonance imaging have the disadvantages of prohibitive cost or ionizing radiation. Recently, body shape based techniques using body scanners and depth cameras, have brought new opportunities for improving body composition estimation by intelligently analyzing body shape descriptors. In this paper, we present a multi-task deep neural network method utilizing a conditional generative adversarial network to predict the pixel level body composition using only 3D body surfaces. The proposed method can predict 2D subcutaneous and visceral fat maps in a single network with a high accuracy. We further introduce an interpreted patch discriminator which optimizes the texture accuracy of the 2D fat maps. The validity and effectiveness of our new method are demonstrated experimentally on TCIA and LiTS datasets. Our proposed approach outperforms competitive methods by at least 41.3% for the whole body fat percentage, 33.1% for the subcutaneous and visceral fat percentage, and 4.1% for the regional fat predictions.
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http://dx.doi.org/10.1016/j.jbi.2021.103866DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355206PMC
August 2021

Bioinformatics Analysis of Candidate Genes and Pathways Related to Hepatocellular Carcinoma in China: A Study Based on Public Databases.

Pathol Oncol Res 2021 26;27:588532. Epub 2021 Mar 26.

Department of Hepatology, Tianjin Second People's Hospital, Tianjin, China.

Hepatocellular carcinoma (HCC) is a highly aggressive malignant tumor of the digestive system worldwide. Chronic hepatitis B virus (HBV) infection and aflatoxin exposure are predominant causes of HCC in China, whereas hepatitis C virus (HCV) infection and alcohol intake are likely the main risk factors in other countries. It is an unmet need to recognize the underlying molecular mechanisms of HCC in China. In this study, microarray datasets (GSE84005, GSE84402, GSE101685, and GSE115018) derived from Gene Expression Omnibus (GEO) database were analyzed to obtain the common differentially expressed genes (DEGs) by R software. Moreover, the gene ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed by using Database for Annotation, Visualization and Integrated Discovery (DAVID). Furthermore, the protein-protein interaction (PPI) network was constructed, and hub genes were identified by the Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape, respectively. The hub genes were verified using Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, and Kaplan-Meier Plotter online databases were performed on the TCGA HCC dataset. Moreover, the Human Protein Atlas (HPA) database was used to verify candidate genes' protein expression levels. A total of 293 common DEGs were screened, including 103 up-regulated genes and 190 down-regulated genes. Moreover, GO analysis implied that common DEGs were mainly involved in the oxidation-reduction process, cytosol, and protein binding. KEGG pathway enrichment analysis presented that common DEGs were mainly enriched in metabolic pathways, complement and coagulation cascades, cell cycle, p53 signaling pathway, and tryptophan metabolism. In the PPI network, three subnetworks with high scores were detected using the Molecular Complex Detection (MCODE) plugin. The top 10 hub genes identified were , , , , , , , , and . The other public databases confirmed that high expression of the aforementioned genes related to poor overall survival among patients with HCC. This study primarily identified candidate genes and pathways involved in the underlying mechanisms of Chinese HCC, which is supposed to provide new targets for the diagnosis and treatment of HCC in China.
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http://dx.doi.org/10.3389/pore.2021.588532DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262246PMC
March 2021

Plasma biomarker profiles and the correlation with cognitive function across the clinical spectrum of Alzheimer's disease.

Alzheimers Res Ther 2021 07 5;13(1):123. Epub 2021 Jul 5.

Institute of Neurology, Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Rd, Shanghai, China.

Background: Plasma biomarkers showed a promising value in the disease diagnosis and management of Alzheimer's disease (AD). However, profiles of the biomarkers and the associations with cognition across a spectrum of cognitive stages have seldom been reported.

Methods: We recruited 320 individuals with cognitive impairment and 131 cognitively normal participants from a memory clinic and a community cohort. Participants were classified into 6 groups based on their Clinical Dementia Rating (CDR) scores and clinical diagnosis, including AD, amnestic mild cognitive impairment (aMCI), and normal cognition (NC). A battery of neuropsychological tests was used to assess the global and domain-specific cognition. Plasma Aβ, Aβ, Aβ/Aβ, total tau (t-tau), neurofilament protein light chain (NfL), and phosphorylated tau at threonine 181 (p-tau181) were quantified using the single-molecule array (Simoa) platform.

Results: All the plasma markers (Aβ, Aβ, Aβ/Aβ, t-tau, NfL, p-tau181) showed certain discrepancies among NC, aMCI, and AD groups. The p-tau181 level showed a continuous escalating trend as the CDR scores increased from 0 (NC group) to 3 (severe AD). Compared with other biomarkers, p-tau181 had correlations with broader cognitive domains, covering global cognition (r = -0.536, P < 0.0001), memory (r = -0.481, P < 0.0001), attention (r = -0.437, P < 0.0001), visuospatial function (r = -0.385, P < 0.0001), and language (r = -0.177, P = 0.0003). Among participants with CDR ≥ 1, higher p-tau181 was correlated with worse global cognition (r = -0.301, P < 0.001).

Conclusions: Plasma p-tau181 had correlations with broader cognitive domains, suggesting its potential as a promising clinical-relevant blood-based biomarker.
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http://dx.doi.org/10.1186/s13195-021-00864-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259165PMC
July 2021

Integrated Analysis of Genomic and Immunological Features in Lung Adenocarcinoma With Micropapillary Component.

Front Oncol 2021 17;11:652193. Epub 2021 Jun 17.

Translational Medicine Research Center, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Cancer Center, Zhejiang University School of Medicine, Hangzhou, China.

Background: Micropapillary adenocarcinoma is one of the most aggressive histologic subtypes of lung adenocarcinoma (LADC), and even a minor proportion of micropapillary component (MPC) within the LADC could contribute to poor prognosis. Comprehensive analysis of genetic and immunological features of LADC with different percentages of MPC would help better understand cancer biology of this LADC subtype and direct future treatments.

Methods: We performed next-generation sequencing (NGS) for a discovery cohort of 43 LADC patients whose tumors were micro-dissected to separate MPC and non-MPC lesions and a reference cohort of 113 LADC patients. MPC-enriched genetic alterations that were detected in the discovery cohort were then confirmed using a validation cohort of 183 LADC patients. Immunological staining was also conducted on the MPC-containing samples in the discovery cohort.

Results: Tumors with a higher percentage of MPC tended to harbor more tumor mutation burdens (TMBs) and chromosome instability (CIN). Some rare genetic events may serve as the genetic landscape to drive micropapillary tumor progression. Specifically, alterations in transcription termination factor 1 (), brain-specific angiogenesis inhibitor 3 (), mammalian target of rapamycin (), and cyclin-dependent kinase inhibitor 2A () were cross-validated to be enriched in MPC-contained LADC. Additionally, tumors with a higher percentage of MPC were associated with a higher percentage of CD4+, CD8+, and PD-L1+ staining, and some genetic changes that were enriched in MPC, including amplification and mutation, were correlated with increased PD-L1 expression.

Conclusion: We identified multiple novel MPC-enriched genetic changes that could help us understand the nature of this aggressive cancer subtype. High MPC tumors tended to have elevated levels of TMBs, T cell infiltration, and immunosuppression than low MPC tumors, implying the potential link between MPC content and sensitivity to immunotherapy.
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http://dx.doi.org/10.3389/fonc.2021.652193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248503PMC
June 2021

CCL24 Protects Renal Function by Controlling Inflammation in Podocytes.

Dis Markers 2021 16;2021:8837825. Epub 2021 Jun 16.

Department of Endocrinology and Genetic Metabolism, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu 241002, China.

Diabetic nephropathy (DN) is one of the most lethal complications of diabetes mellitus with chronic inflammation. We have examined the role of the inflammatory chemokine CCL24 in DN. We observed that serum levels of CCL24 were significantly elevated in patients with DN. Not only that, the expression of CCL24 was significantly increased in the kidneys of DN mice. The kidney of DN mice showed increased renal fibrosis and inflammation. We characterized an in vitro podocyte cell model with high glucose. Western blot analysis showed that expression of CCL24 was significantly increased under high-glucose conditions. Stimulation with high glucose (35 mmol/L) resulted in an increase in CCL24 expression in the first 48 hours but changed little after 72 hours. Moreover, with glucose stimulation, the level of podocyte fibrosis gradually increased, the expression of the proinflammatory cytokine IL-1 was upregulated, and the expression of the glucose transporter GLUT4, involved in the insulin signal regulation pathway, also increased. It is suggested that CCL24 is involved in the pathogenesis of DN. In order to study the specific role of CCL24 in this process, we used the CRISPR-Cas9 technique to knock out CCL24 expression in podocytes. Compared with the control group, the podocyte inflammatory response induced by high glucose after CCL24 knockout was significantly increased. These results suggest that CCL24 plays a role in the development of early DN by exerting an anti-inflammatory effect, at least, in podocytes.
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http://dx.doi.org/10.1155/2021/8837825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221868PMC
June 2021

serves as a prognostic factor of breast cancer and promotes cell proliferation through activating AKT/mTORC1 signaling pathway.

Ann Transl Med 2021 May;9(10):892

Department of Oncology, School of Medicine, Southeast University, Nanjing, China.

Background: The purpose of our research was to determine if the clinical, pathological, and prognostic functions of are the same as those of other molecular breast cancer (BC) subgroups.

Methods: We used the Oncomine and The Cancer Genome Atlas (TCGA) online databases to examine the expression and genetic changes of in BC tissues. Immunohistochemical analysis was used to validate the protein expression in subtypes of BC, while Kaplan-Meier figures and log-rank tests were used to evaluate the prognostic relevance of . Uni- and multivariate Cox regression models were adapted to analyze hazard ratios (HRs) and the independent prognostic factors. We analyzed the alterations of different malignancies of luminal cells by up-regulation of in human luminal cell lines MCF-7. was overexpressed in luminal cells, and then the AKT, mTOR, and p70-S6K phosphorylation and expression were analyzed by western blot analysis and real-time quantitative polymerase chain reaction (qPCR).

Results: Our results suggested that was overexpressed in BC cell lines and in patients' tissues. Elevated messenger RNA (mRNA) and protein expression was correlated to a worse clinical prognosis (P<0.001) in luminal subtypes of BC. The multivariate analysis suggested that high level of expression could be an independent prognostic factor for decreased overall survival (OS). The study also demonstrated that overexpression increased proliferation of MCF-7 cells by reducing the cell cycle arrest in G1 phase. Our mechanistic study further indicates that enhances the proliferation of the MCF-7 cell by activation of AKT/mTORC1 pathway through phosphorylation.

Conclusions: Our study demonstrated that may have a vital function in the biology of BC cells, indicating that is a potential prognostic biomarker and may be a valuable therapeutic target in BC patients.
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http://dx.doi.org/10.21037/atm-21-2247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184433PMC
May 2021

No significant association of repeated messages with changes in health compliance in the COVID-19 pandemic: a registered report on the extended parallel process model.

PeerJ 2021 3;9:e11559. Epub 2021 Jun 3.

Faculty of Arts and Science, Kyushu University, Fukuoka, Fukuoka, Japan.

When people are confronted with health proposals during the coronavirus disease 2019 (COVID-19) pandemic, it has been suggested that fear of COVID-19 can serve protective functions and ensure public health compliance. However, health proposal repetition and its perceived efficacy also influence the behavior intention toward the proposal, which has not yet been confirmed in the COVID-19 context. The present study examined whether the extended parallel process model (EPPM) could be generalized to a naturalistic context like the COVID-19 pandemic. Additionally, we explored how repetition of a health proposal is involved with the EPPM. In this study, two groups of participants were exposed to the same health proposal related to COVID-19, where one group was exposed once and another group twice. Participants then filled out a questionnaire consisting of items concerning behavior intention and adapted from the Risk Behavior Diagnosis Scale. Structural equation modeling was used to determine the multivariate associations between the variables. Although the results showed that behavior intention is predicted by perceived efficacy, no significant influence of perceived threat was detected. Furthermore, no significant effect of repetition was found toward either response efficacy or perceived susceptibility. These findings indicate that to promote health compliance during the COVID-19 pandemic, it is more efficient to focus on health proposals' perceived efficacy rather than the disease's perceived threat. For future health communication research, the present study suggests improved analysis strategies and repeated manipulation of messages.
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http://dx.doi.org/10.7717/peerj.11559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180189PMC
June 2021

Clearance of circulating tumor DNA in a high-risk stage-IV rectal carcinoma patient with synchronous liver metastases after conversion surgery is correlated with pathologic complete response.

Ther Adv Gastrointest Endosc 2021 Jan-Dec;14:26317745211020279. Epub 2021 Jun 2.

Key Laboratory of Carcinogenesis and Translational Research, Hepatopancreatobiliary Surgery Department I, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, China.

Colorectal cancer is the third most common cancer worldwide, and its incidence continues to grow. Approximately one-third of patients with colorectal cancer develop liver metastases during the natural course of disease. Complete surgical resection is associated with very low mortality in colorectal liver metastasis patients, but only a small fraction of colorectal liver metastasis patients fulfill the selection criteria for surgical treatment. We herein describe a high-risk stage-IV rectal carcinoma patient who was initially unresectable according to the National Comprehensive Cancer Network guidelines with a clinical risk score of 4 but received conversion surgery combined with systemic chemotherapy and achieved a favorable long-term clinical outcome (pathologic complete response) of approximately 28 months. Furthermore, serial circulating tumor DNA monitoring using next-generation sequencing provided a comprehensive view of the patient's clinical and pathologic status for better clinical decision support over the course of the disease. The absence of circulating tumor DNA/cells after conversion surgery was correlated with pathologic complete response. This case study not only demonstrated that a curative oncosurgical approach could be considered for high-risk colorectal liver metastasis patients under specific circumstances but also highlighted the role of circulating tumor DNA monitoring to gain further insight into the evolution of a patient's response over time.
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http://dx.doi.org/10.1177/26317745211020279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175825PMC
June 2021

SIRT1/PGC-1α signaling activation by mangiferin attenuates cerebral hypoxia/reoxygenation injury in neuroblastoma cells.

Eur J Pharmacol 2021 Sep 9;907:174236. Epub 2021 Jun 9.

Xi'an Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Xi'an No.3 Hospital, School of Life Sciences and Medicine, Northwest University, 10 Fengcheng Three Road, Xi'an, China; Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education. Faculty of Life Sciences, Northwest University, 229 Taibai North Road, Xi'an, China. Electronic address:

Ischemia reperfusion injury (IRI) is associated with poor prognoses in the setting of ischemic brain diseases. Silence information regulator 1 (SIRT1) is a member of the third class of nicotinamide adenine dinucleotide (NAD)-dependent sirtuins. Recently, the role of SIRT1/peroxisome proliferators-activated receptor-γ coactivator 1α (PGC-1α) pathway in organ (especially the brain) protection under various pathological conditions has been widely investigated. Mangiferin (MGF), a natural C-glucosyl xanthone polyhydroxy polyphenol, has been shown to be beneficial to several nervous system diseases and the protective effects of MGF can be achieved through the regulation of SIRT1 signaling. This study is designed to investigate the protective effects of MGF treatment in the setting of cerebral IRI and to elucidate the potential mechanisms. We first evaluated the toxicity of MGF and chose the safe concentrations for the following experiments. MGF exerted obvious neuroprotection against hypoxia/reoxygenation (HR)-induced injury, indicated by restored cell viability and cell morphology, decreased lactate dehydrogenase (LDH) release and reactive oxygen species generation. MGF also restored the protein expressions of SIRT1, PGC-1α, Nrf2, NQO1, HO-1, NRF1, UCP2, and Bcl2 down-regulated by HR treatment. However, SIRT1 siRNA could reverse MGF-induced neuroprotection and decrease the expressions of molecules mentioned above. Taken together, our findings suggest that MGF treatment exerts neuroprotection against HR injury via activating SIRT1/PGC-1α signaling. These findings may provide a theoretical basis for the exploitation of MGF as a potential neuroprotective drug candidate, which may be beneficial for the ischemic stroke patients in clinic.
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http://dx.doi.org/10.1016/j.ejphar.2021.174236DOI Listing
September 2021

Excited-State Switching in Rhenium(I) Bipyridyl Complexes with Donor-Donor and Donor-Acceptor Substituents.

J Am Chem Soc 2021 Jun 11;143(24):9082-9093. Epub 2021 Jun 11.

Department of Chemistry, University of Otago, Dunedin 9016, New Zealand.

The optical properties of two Re(CO)(bpy)Cl complexes in which the bpy is substituted with two donor (triphenylamine, TPA, ReTPA) as well as both donor (TPA) and acceptor (benzothiadiazole, BTD, ReTPA-BTD) groups are presented. For ReTPA the absorption spectra show intense intraligand charge-transfer (ILCT) bands at 460 nm with small solvatochromic behavior; for ReTPA-BTD the ILCT transitions are weaker. These transitions are assigned as TPA → bpy transitions as supported by resonance Raman data and TDDFT calculations. The excited-state spectroscopy shows the presence of two emissive states for both complexes. The intensity of these emission signals is modulated by solvent. Time-resolved infrared spectroscopy definitively assigns the excited states present in CHCl to be MLCT in nature, and in MeCN the excited states are ILCT in nature. DFT calculations indicated this switching with solvent is governed by access to states controlled by spin-orbit coupling, which is sufficiently different in the two solvents, allowing to select out each of the charge-transfer states.
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http://dx.doi.org/10.1021/jacs.1c02755DOI Listing
June 2021
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