Publications by authors named "Jun Ding"

547 Publications

Circβ-catenin promotes tumor growth and Warburg effect of gallbladder cancer by regulating STMN1 expression.

Cell Death Discov 2021 Sep 6;7(1):233. Epub 2021 Sep 6.

Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.

Gallbladder cancer (GBC) is the most malignant cancer of the biliary tract cancer and presents poor prognosis. CircRNAs have been identified as critical regulators of multiple stages in tumor progression. In the study, we first demonstrated that circular RNA circβ-catenin expression was upregulated in GBC tissues when compared to adjacent normal tissues and associated with advanced clinical stage and poor prognosis in GBC patients. Silencing of circβ-catenin obviously suppressed GBC cell proliferation and cell cycle progression in vitro, but circβ-catenin overexpression had the opposite effects. In vivo, silencing of circβ-catenin inhibited tumor growth. Furthermore, we also found that circβ-catenin promoted GBC cell lactate production, pyruvate production, ATP quantity, and extracellular acidification rate (ECAR), which suggested that circβ-catenin regulated Warburg effect in GBC. Mechanistic analysis further highlighted that circβ-catenin promoted Stathmin 1 (STMN1) expression through sponging miR-223 in GBC progression. In addition, knockdown of STMN1 inhibited cell growth and Warburg effect in GBC. In summary, our findings indicated that circβ-catenin/miR-223/STMN1 axis could regulate cell growth and Warburg effect in GBC. Targeting circβ-catenin might be a potential therapeutic strategy for GBC.
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http://dx.doi.org/10.1038/s41420-021-00626-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421404PMC
September 2021

CRB-SWATH: A Method for Enhancing Untargeted Precursor Ion Extraction and Automatically Constructing Their Tandem Mass Spectra from SWATH Datasets by Chromatographic Retention Behaviors.

Anal Chem 2021 09 30;93(36):12273-12280. Epub 2021 Aug 30.

Department of Chemistry, Wuhan University, Wuhan 430072, People's Republic of China.

Sequential window acquisition of all theoretical spectra (SWATH) as a typical data-independent acquisition (DIA) strategy is favorable for untargeted metabolomics. It could theoretically acquire product ions of all precursor ions, including precursor ions showing chromatographic peaks of rather poor qualities. However, existing data processing methods present limited capabilities in capturing poor-quality peaks of precursor ions. Thus, although their product ions could be acquired, their precursor ions are absent. Here, we present a new strategy, chromatographic retention behavior-SWATH (CRB-SWATH), that could unbiasedly capture poor-quality peaks and provide high resolutions of multiplexed mass spectroscopy (MS/MS) spectra in SWATH datasets. CRB-SWATH monitors CRBs of SWATH-MS signals under a series of altered elution gradients. As signals of compounds differ from noise by showing CRBs, both the precursor and fragment ions are captured, while ignoring their peak qualities. Moreover, CRB-SWATH offers good chances to resolve highly multiplexed MS/MS spectra in SWATH datasets because precursor ions coeluted in a single elution gradient often present different CRBs. In the untargeted metabolic analysis of cell extracts, CRB-SWATH showed the advantage in exclusively capturing 2645 ions of poor-quality peaks (i.e., tiny peaks, discontinuous ion traces, tailing peaks, zigzag peaks, etc.), accounting for 34.4% of all the untargeted precursor ions extracted. Therein, it is noteworthy that among 2116 negative ions detected in hydrophilic interaction liquid chromatography (HILIC) mode, 1284 poor-quality ion peaks (>60%) were exclusively captured by CRB-SWATH. As CRB-SWATH automatically captures a large sum of true ion peaks of poor qualities, extracts MS/MS spectra of high purities, and provides chromatographic retention behaviors of untargeted metabolites for identification and classification, it could be a useful metabolomics tool for understanding biological phenomena better.
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http://dx.doi.org/10.1021/acs.analchem.1c01841DOI Listing
September 2021

Enhancing motor learning by increasing the stability of newly formed dendritic spines in the motor cortex.

Neuron 2021 Aug 20. Epub 2021 Aug 20.

Department of Neurosurgery, Stanford University, Stanford, CA 94305, USA; Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA; Stanford Bio-X, Stanford University, Stanford, CA 94305, USA. Electronic address:

Dendritic spine dynamics are thought to be substrates for motor learning and memory, and altered spine dynamics often lead to impaired performance. Here, we describe an exception to this rule by studying mice lacking paired immunoglobulin receptor B (PirB). Pyramidal neuron dendrites in PirB mice have increased spine formation rates and density. Surprisingly, PirB mice learn a skilled reaching task faster than wild-type (WT) littermates. Furthermore, stabilization of learning-induced spines is elevated in PirB mice. Mechanistically, single-spine uncaging experiments suggest that PirB is required for NMDA receptor (NMDAR)-dependent spine shrinkage. The degree of survival of newly formed spines correlates with performance, suggesting that increased spine stability is advantageous for learning. Acute inhibition of PirB function in M1 of adult WT mice increases the survival of learning-induced spines and enhances motor learning. These results demonstrate that there are limits on motor learning that can be lifted by manipulating PirB, even in adulthood.
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http://dx.doi.org/10.1016/j.neuron.2021.07.030DOI Listing
August 2021

Comparative lipidomics profiling of the sea urchin, Strongylocentrotus intermedius.

Comp Biochem Physiol Part D Genomics Proteomics 2021 Aug 16;40:100900. Epub 2021 Aug 16.

Key Laboratory of Mariculture & Stock Enhancement in North China's Sea, Ministry of Agriculture and Rural Affairs, Dalian Ocean University, Dalian 116023, China. Electronic address:

Strongylocentrotus intermedius is an edible sea urchin and well-known for its nutritional value, such as a high content of polyunsaturated fatty acids (PUFAs). We carried out an untargeted lipidomics via high-resolution ultra-high-performance liquid chromatography - mass spectrometry (UPLC-MS) to highlight the features of the lipids profile of sea urchin gonad, which allowed for a more detailed interpretation of the accumulation of PUFAs with different abundances among sea urchins. For the first time, lipidomics profiling of lipid abundances in S. intermedius was demonstrated. We detected 11 PUFAs in sea urchin gonads, which represented >54.13% of the total fatty acid content. A total of 1552 lipid molecular species belonging to 36 lipid classes were identified. Lipidomics profiles data were analyzed using orthogonal partial least squares discriminant analysis (OPLS-DA) model and distinguished the PUFA abundances in both sexes of sea urchins. The significant differences in lipid molecules were highlighted and the major lipid classes identified were phosphatidylcholine (PC [19 species]) among females and triglycerides (TG [11 species]) among males. PC (42: 11) may be used as a potential marker for distinguishing high levels of PUFAs in sea urchin individuals, which as the result of the high level of PC (42:11). These data enrich the lipid profile library of aquatic products and provide a more reliable and refined biomarkers for the further research on fatty acid synthesis and metabolism in aquatic animals.
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http://dx.doi.org/10.1016/j.cbd.2021.100900DOI Listing
August 2021

A novel immune signature to predict the prognosis of patients with hepatocellular carcinoma.

Medicine (Baltimore) 2021 Aug;100(33):e26948

Department of Hepatobiliary Surgery, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, China.

Abstract: Aberrant immunity has been associated with the initiation and progression of cancers such as hepatocellular carcinoma (HCC). Here, we aim to develop a signature based on immune-related genes (IRGs) to predict the prognosis of HCC patients. The gene expression profiles of 891 HCC samples were derived from 4 publicly accessible datasets. A total of 1534 IRGs from Immunology Database and Analysis Portal website were obtained as candidate genes for prognostic assessment. Using least absolute shrinkage and selection operator (LASSO) regression analysis, 12 IRGs were selected as prognostic biomarkers and were then aggregated to generate an IRG score for each HCC sample. In the training dataset (n = 365), patients with high IRG scores showed a remarkably poorer overall survival than those with low IRG scores (log-rank P < .001). Similar results were documented in 3 independent testing datasets (n = 226, 221, 79, respectively). Multivariate Cox regression and stratified analyses indicated that the IRG score was an independent and robust signature to predict the overall survival in HCC patients. Patients with high IRG scores tended to be in advanced TNM stages, with increased risks of tumor recurrence and metastasis. More importantly, the IRG score was strongly associated with certain immune cell counts, gene expression of immune checkpoints, estimated immune score, and mutation of critical genes in HCC. In conclusion, the proposed IRG score can predict the prognosis and reflect the tumor immune microenvironment of HCC patients, which may facilitate the individualized treatment and provide potential immunotherapeutic targets.
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http://dx.doi.org/10.1097/MD.0000000000026948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8376334PMC
August 2021

Atomistic simulations of dislocation mobility in refractory high-entropy alloys and the effect of chemical short-range order.

Nat Commun 2021 Aug 11;12(1):4873. Epub 2021 Aug 11.

Materials Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.

Refractory high-entropy alloys (RHEAs) are designed for high elevated-temperature strength, with both edge and screw dislocations playing an important role for plastic deformation. However, they can also display a significant energetic driving force for chemical short-range ordering (SRO). Here, we investigate mechanisms underlying the mobilities of screw and edge dislocations in the body-centered cubic MoNbTaW RHEA over a wide temperature range using extensive molecular dynamics simulations based on a highly-accurate machine-learning interatomic potential. Further, we specifically evaluate how these mechanisms are affected by the presence of SRO. The mobility of edge dislocations is found to be enhanced by the presence of SRO, whereas the rate of double-kink nucleation in the motion of screw dislocations is reduced, although this influence of SRO appears to be attenuated at increasing temperature. Independent of the presence of SRO, a cross-slip locking mechanism is observed for the motion of screws, which provides for extra strengthening for refractory high-entropy alloy system.
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http://dx.doi.org/10.1038/s41467-021-25134-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8357793PMC
August 2021

The Cardamine enshiensis genome reveals whole genome duplication and insight into selenium hyperaccumulation and tolerance.

Cell Discov 2021 Aug 10;7(1):62. Epub 2021 Aug 10.

Hubei Minzu University Affiliated Enshi Clinical Medical School, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei, China.

Cardamine enshiensis is a well-known selenium (Se)-hyperaccumulating plant. Se is an essential trace element associated with many health benefits. Despite its critical importance, genomic information of this species is limited. Here, we report a chromosome-level genome assembly of C. enshiensis, which consists of 443.4 Mb in 16 chromosomes with a scaffold N50 of 24 Mb. To elucidate the mechanism of Se tolerance and hyperaccumulation in C. enshiensis, we generated and analyzed a dataset encompassing genomes, transcriptomes, and metabolomes. The results reveal that flavonoid, glutathione, and lignin biosynthetic pathways may play important roles in protecting C. enshiensis from stress induced by Se. Hi-C analysis of chromatin interaction patterns showed that the chromatin of C. enshiensis is partitioned into A and B compartments, and strong interactions between the two telomeres of each chromosome were correlated with histone modifications, epigenetic markers, DNA methylation, and RNA abundance. Se supplementation could affect the 3D chromatin architecture of C. enshiensis at the compartment level. Genes with compartment changes after Se treatment were involved in selenocompound metabolism, and genes in regions with topologically associated domain insulation participated in cellular responses to Se, Se binding, and flavonoid biosynthesis. This multiomics research provides molecular insight into the mechanism underlying Se tolerance and hyperaccumulation in C. enshiensis.
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http://dx.doi.org/10.1038/s41421-021-00286-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8352907PMC
August 2021

Se-Methylselenocysteine Alleviates Liver Injury in Diethylnitrosamine (DEN)-Induced Hepatocellular Carcinoma Rat Model by Reducing Liver Enzymes, Inhibiting Angiogenesis, and Suppressing Nitric Oxide (NO)/Nitric Oxide Synthase (NOS) Signaling Pathway.

Med Sci Monit 2021 Aug 4;27:e929255. Epub 2021 Aug 4.

Department of Hepatobiliary Surgery, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei, China (mainland).

BACKGROUND Hepatocellular carcinoma is the third leading cause of cancer-associated mortality. This study aimed to investigate the effects of se-methylselenocysteine (MSC) on oncogenesis of diethylnitrosamine (DEN)-induced hepatocellular carcinoma. MATERIAL AND METHODS A hepatocellular carcinoma rat model was established by administering DEN. Rat models were divided into Model (0.1 mg/kg MSC), Model+0.3 mg/kg MSC, Model+1 mg/kg MSC, and Model+3 mg/kg MSC groups. A Normal control group consisted of mice not administered MSC. Hematoxylin and eosin staining was used to determine liver injury. Immunohistochemical analysis was conducted to identify CD34 and vascular endothelial growth factor (VEGF) expression. VEGF gene transcription was detected with RT-PCR. Biochemical analyses were performed to determine alanine aminotransferase, aspartate aminotransferase, total bilirubin, γ-glutamyl transpeptidase, alkaline phosphatase, and albumin levels in serum, and nitric oxide (NO)/nitric oxide synthase (NOS) levels in liver tissues. Transmission electron microscopy was used to observe the ultra-microstructures of hepatocytes. RESULTS MSC treatment markedly alleviated liver injury and nuclear lesions in the treatment groups compared to the Model group. MSC treatment significantly improved liver functions in the treatment groups compared to the Model group (P<0.05). MSC treatment significantly decreased CD34 expression and NO and NOS levels in liver tissues and suppressed VEGF expression compared to the Model group (all P<0.05). CONCLUSIONS MSC administration alleviated liver injury in a DEN-induced hepatocellular carcinoma rat model through reducing liver enzymes, inhibiting angiogenesis, and suppressing the NO/NOS signaling pathway.
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http://dx.doi.org/10.12659/MSM.929255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8351367PMC
August 2021

Association of Red Meat and Poultry Consumption With the Risk of Metabolic Syndrome: A Meta-Analysis of Prospective Cohort Studies.

Front Nutr 2021 8;8:691848. Epub 2021 Jul 8.

Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, China.

This study aims to investigate the association of red meat (processed and unprocessed) and poultry consumption with the risk of metabolic syndrome (MetS). Prospective cohort studies on the association of red meat (processed and unprocessed) and poultry consumption with the risk of MetS were identified by comprehensive literature search in the PubMed, Web of Science, and Embase databases up to March 2021. The pooled relative risk (RR) of MetS with 95% CIs for the highest vs. lowest category of red meat or poultry consumption was extracted for meta-analysis. A total of nine prospective cohort studies were included in this study. Among them, eight studies were identified for red meat consumption. The overall multi-variable adjusted RR demonstrated that red meat consumption was associated with a higher risk of MetS (RR = 1.35, 95% CI: 1.13-1.62; = 0.001). Moreover, four and three studies were specifically related to processed and unprocessed red meat consumption, respectively. Both processed (RR = 1.48, 95% CI: 1.11-1.97; = 0.007) and unprocessed red meat (RR = 1.32, 95% CI: 1.14-1.54; = 0.0003) consumption was associated with a higher risk of MetS. With regard to poultry consumption, three studies were included. The overall multi-variable adjusted RR suggested that poultry consumption was associated with lower risk of MetS (RR = 0.85, 95% CI: 0.75-0.97; = 0.02). The current evidence indicates that red meat (processed and unprocessed) consumption is associated with a higher risk of MetS, whereas, poultry consumption is associated with a lower risk of MetS. More well-designed randomized controlled trials are still needed to address the issues further.
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http://dx.doi.org/10.3389/fnut.2021.691848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295459PMC
July 2021

Presence and transmission of mitochondrial heteroplasmic mutations in human populations of European and African ancestry.

Mitochondrion 2021 Jul 21;60:33-42. Epub 2021 Jul 21.

Framingham Heart Study, Framingham, MA 01702, USA; Population Sciences Branch, NHLBI/NIH, Bethesda, MD 20892, USA.

We investigated the concordance of mitochondrial DNA heteroplasmic mutations (heteroplasmies) in 6745 maternal pairs of European (EA, n = 4718 pairs) and African (AA, n = 2027 pairs) Americans in whole blood. Mother-offspring pairs displayed the highest concordance rate, followed by sibling-sibling and more distantly-related maternal pairs. The allele fractions of concordant heteroplasmies exhibited high correlation (R = 0.8) between paired individuals. Discordant heteroplasmies were more likely to be in coding regions, be nonsynonymous or nonsynonymous-deleterious (p < 0.001). The number of deleterious heteroplasmies was significantly correlated with advancing age (20-44, 45-64, and ≥65 years, p-trend = 0.01). One standard deviation increase in heteroplasmic burden (i.e., the number of heteroplasmies carried by an individual) was associated with 0.17 to 0.26 (p < 1e - 23) standard deviation decrease in mtDNA copy number, independent of age. White blood cell count and differential count jointly explained 0.5% to 1.3% (p ≤ 0.001) variance in heteroplasmic burden. A genome-wide association and meta-analysis identified a region at 11p11.12 (top signal rs779031139, p = 2.0e - 18, minor allele frequency = 0.38) associated with the heteroplasmic burden. However, the 11p11.12 region is adjacent to a nuclear mitochondrial DNA (NUMT) corresponding to a 542 bp area of the D-loop. This region was no longer significant after excluding heteroplasmies within the 542 bp from the heteroplasmic burden. The discovery that blood mtDNA heteroplasmies were both inherited and somatic origins and that an increase in heteroplasmic burden was strongly associated with a decrease in average number of mtDNA copy number in blood are important findings to be considered in association studies of mtDNA with disease traits.
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http://dx.doi.org/10.1016/j.mito.2021.07.004DOI Listing
July 2021

A boronic acid-modified C derivatization reagent for the rapid detection of 3-monochloropropane-1,2-diol using matrix-assisted laser desorption/ionization-mass spectrometry.

Rapid Commun Mass Spectrom 2021 Oct;35(19):e9169

Department of Chemistry, Wuhan University, Wuhan, China.

Rationale: 3-Monochloropropane-1,2-diol (3-MCPD) is a well-known contaminant formed in food thermal processing, which could be found in a variety of foodstuffs. Due to its potential carcinogenicity, it was essential to quickly develop a rapid and high-throughput analytical method to monitor 3-MCPD in foodstuffs, which is described in this study.

Methods: 3-MCPD was extracted from foodstuffs and then was derivatized with a boronic acid-modified C (B-C ) through the boronic acid-diol reaction. Microwave heating was used to accelerate the derivatization reaction. Mass spectrometry (MS) analysis was conducted using matrix-assisted laser desorption/ionization-MS (MALDI-MS). The application of the method was validated using various smoked food samples.

Results: The chemical derivatization of 3-MCPD with B-C enabled the addition of a C -tag to 3-MCPD. High-throughput analysis of the sample within 0.5 h was realized. A good linear range from 0.02 to 1.5 μg mL for 3-MCPD was obtained, with a detection limit of 0.005 μg mL . The recoveries in spiked foodstuffs ranged from 85.4% to 115.1% with relative standard deviations of 2.0%-14.2%. This method was successfully applied to detect 3-MCPD in smoked foodstuffs.

Conclusions: A quantitative method was developed for the detection of 3-MCPD in foodstuffs using B-C derivatization combined with MALDI-MS strategy. This proposed method may serve as a potential platform for the rapid and high-throughput analysis of 3-MCPD in foodstuffs for the purpose of food safety control.
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http://dx.doi.org/10.1002/rcm.9169DOI Listing
October 2021

Serum Copper and Zinc Levels and Colorectal Cancer in Adults: Findings from the National Health and Nutrition Examination 2011-2016.

Biol Trace Elem Res 2021 Jul 20. Epub 2021 Jul 20.

Department of Anesthesiology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, 185, Pu An Road, Shanghai, 201203, China.

Several studies have indicated an association between serum copper and zinc levels and colorectal cancer, but results were controversial. This study assessed the association of serum copper, zinc, and copper/zinc ratio with colorectal cancer in US adults aged 20 years and older through the use of National Health and Nutrition Examination Survey (NHANES) 2011-2016 data. Serum concentrations of copper and zinc were measured using inductively coupled plasma dynamic reaction cell mass spectrometry (ICP-DRC-MS). Odds ratios with 95% confidence intervals (ORs with CIs) were calculated for serum copper, zinc, and copper/zinc ratio by multivariate logistic regression. A total of 4663 participants (2320 males and 2343 females) with 24 colorectal cancer patients were included in the analyses. We did not observe a statistically significant association between serum copper level and colorectal cancer (top vs bottom quartile multivariate OR 1.71; 95% CI, 0.37-7.88; P for trend = 0.429). In addition, serum zinc level was also not significantly associated with colorectal cancer (top vs bottom quartile multivariate OR 0.72; 95% CI, 0.12-4.27; P for trend = 0.346). While in the age- and gender-adjusted model, there seemed to be a trend that participants with higher copper/zinc ratio level had higher odds of colorectal cancer than participants with lower copper/zinc ratio level; no statistically significant association was observed in multivariate-adjusted models. Our findings did not support a significant association between serum copper and zinc level and colorectal cancer risk in the general US population. Furthermore, large longitudinal studies should be needed to confirm these findings.
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http://dx.doi.org/10.1007/s12011-021-02826-8DOI Listing
July 2021

Associations of Whole Grain and Refined Grain Consumption With Metabolic Syndrome. A Meta-Analysis of Observational Studies.

Front Nutr 2021 1;8:695620. Epub 2021 Jul 1.

Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, China.

The associations of whole grain and refined grain consumption with metabolic syndrome (MetS) has been evaluated in several epidemiological studies with conflicting results. This meta-analysis was therefore employed to further investigate the above associations. We searched the PubMed, Web of Science and Embase database until March 2021 (without restriction for inclusion time), for observational studies on the associations of whole grain and refined grain consumption with MetS. The pooled relative risk (RR) of MetS for the highest vs. lowest category of whole grain and refined grain consumption, as well as their corresponding 95% confidence interval (CI) were calculated. A total of 14 observational studies, which involved seven cross-sectional and seven prospective cohort studies, were identified. Specifically, nine studies were related to whole grain consumption, and the overall multi-variable adjusted RR demonstrated that the whole grain consumption was inversely associated with MetS (RR = 0.80, 95%CI: 0.67-0.97; = 0.021). With regard to refined grain consumption, 13 studies were included. The overall multi-variable adjusted RR indicated that refined grain consumption was positively associated with MetS (RR = 1.37, 95%CI: 1.02-1.84; = 0.036). The existing evidence suggests that whole grain consumption is negatively associated with MetS, whereas refined grain consumption is positively associated with MetS. Our result might be helpful to better consider the diet effect on MetS. However, more well-designed prospective cohort studies are needed to elaborate the concerned issues further.
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http://dx.doi.org/10.3389/fnut.2021.695620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280517PMC
July 2021

Measurement of the Hand Transmitted Vibration of the Human Hand Arm System During Operation of a Hand Tractor.

J Vis Exp 2021 Jun 16(172). Epub 2021 Jun 16.

School of Mechanical Engineering, Chongqing University of Technology.

Operators of hand tractors are exposed to high levels of hand transmitted vibration (HTV). This vibration, which can be both irksome and hazardous to human health, is imparted to the operator via his or her hands and arms. However, a standardized method for measuring HTV of hand tractors has yet to be defined. The aim of the study was to present an experimental method for the investigation of the biodynamic response and vibration transmissibility of the hand-arm system during the operation of a hand tractor in a stationary mode. Measurements were performed with ten subjects using three grip forces and three handle vibration levels to examine the influences of the hand pressure and frequency on hand transmitted vibration (HTV). The results indicate that the tightness of grip on the handle influences the vibration response of the hand-arm system, especially at frequencies between 20 and 100 Hz. The transmission of lower frequencies in the hand-arm system was relatively unattenuated. In comparison, attenuation was found to be quite marked for higher frequencies during the operation of the hand tractor. The vibration transmissibility to different parts of the hand-arm system decreased with the increase of the distance from the vibration source. The proposed methodology contributes to the collection of consistent data for the evaluation of operator vibration exposure and the ergonomics development of hand tractors.
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http://dx.doi.org/10.3791/62508DOI Listing
June 2021

Establishment of Carotid Artery Dissection and MRI Findings in a Swine Model.

Front Neurol 2021 16;12:669276. Epub 2021 Jun 16.

Department of Neurology, Southwest Hospital, Third Military Medical University, Chongqing, China.

Carotid artery dissection (CAD) is the leading cause of ischemic stroke in young patients; however, the etiology and pathophysiology of CAD remain largely unknown. In our study, two types of dissections (length × width: 1.5 cm × 1/3 circumference of intima, Group I, = 6; or 1.5 cm × 2/3 circumference of intima, Group II, = 6) were created between the media and intima. Ultrasound (within 2 h after dissection) showed a dissociated intima in the lumen and obstructed blood flow in the surgical area. Digital subtraction angiography (DSA, 72 h after dissection), magnetic resonance imaging (MRI, 72 h after dissection), and hematoxylin-eosin (H&E, 7 days after dissection) staining confirmed stenosis (33.67 ± 5.66%) in Group I and total occlusion in Group II. In 10 out of 12 swine, the CAD model was established using a detacher and balloon dilation, and morphological outcomes (stenosis or occlusion) after CAD were determined by the size of intimal incision.
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http://dx.doi.org/10.3389/fneur.2021.669276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242238PMC
June 2021

Ratiometric fluorescent sensor based on MoS QDs and AuNCs for determination and bioimaging of alkaline phosphatase.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Dec 17;262:120087. Epub 2021 Jun 17.

College of Chemistry, Jilin Province Research Center for Engineering and Technology of Spectral Analytical Instruments, Jilin University, Qianjin Street 2699, Changchun 130012, China. Electronic address:

Herein, a ratiometric fluorescent sensor based on MoS quantum dots (QDs) and glutathione-capped gold nanoclusters (AuNCs) was developed for determination and imaging of alkaline phosphatase (ALP). The sensor was developed by covalently linking QDs with AuNCs to form stable [email protected] nanohybrids that exhibited the blue fluorescence of MoS QDs and the red fluorescence of AuNCs. In the presence of Ce, the fluorescence intensity of AuNCs was increased due to the aggregation-induced emission enhancement (AIEE), while that of MoS QDs remained unchanged, thus could be used as a reference signal. After adenosine 5'-monophosphate (AMP) and ALP were introduced into the system, AMP was hydrolyzed to adenosine and phosphate ions (PO). Owing to higher affinity between Ce and PO, the AIEE effect was inhibited, in turn resulting in the decrease of AuNCs fluorescence. The developed ratiometric fluorescent sensor had a linear response to ALP concentration ranging from 0.5 to 50 U L with a detection limit (LOD) of 0.08 U L. Moreover, the sensor had low cytotoxicity and was successfully employed in lysosome localization and bioimaging of intracellular ALP in living cells.
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http://dx.doi.org/10.1016/j.saa.2021.120087DOI Listing
December 2021

Tumor Microenvironment Characteristics of Pancreatic Cancer to Determine Prognosis and Immune-Related Gene Signatures.

Front Mol Biosci 2021 8;8:645024. Epub 2021 Jun 8.

Department of Hepatobiliary and Pancreatic Surgery, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Pancreatic cancer (PC) is one of the most lethal types of cancer with extremely poor diagnosis and prognosis, and the tumor microenvironment plays a pivotal role during PC progression. Poor prognosis is closely associated with the unsatisfactory results of currently available treatments, which are largely due to the unique pancreatic tumor microenvironment (TME). In this study, a total of 177 patients with PC from The Cancer Genome Atlas (TCGA) cohort and 65 patients with PC from the GSE62452 cohort in Gene Expression Omnibus (GEO) were included. Based on the proportions of 22 types of infiltrated immune cell subpopulations calculated by cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT), the TME was classified by K-means clustering and differentially expressed genes (DEGs) were determined. A combination of the elbow method and the gap statistic was used to explore the likely number of distinct clusters in the data. The ConsensusClusterPlus package was utilized to identify radiomics clusters, and the samples were divided into two subtypes. Survival analysis showed that the patients with TMEscore-high phenotype had better prognosis. In addition, the TMEscore-high had better inhibitory effect on the immune checkpoint. A total of 10 miRNAs, 311 DEGs, and 68 methylation sites related to survival were obtained, which could be biomarkers to evaluate the prognosis of patients with pancreatic cancer. Therefore, a comprehensive description of TME characteristics of pancreatic cancer can help explain the response of pancreatic cancer to immunotherapy and provide a new strategy for cancer treatment.
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http://dx.doi.org/10.3389/fmolb.2021.645024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217872PMC
June 2021

Polyphenol-assisted facile assembly of bioactive nanoparticles for targeted therapy of heart diseases.

Biomaterials 2021 08 9;275:120952. Epub 2021 Jun 9.

Department of Pharmaceutics, College of Pharmacy, Third Military Medical University (Army Medical University), Chongqing 400038, China; State Key Lab of Trauma, Burn and Combined Injury, Third Military Medical University (Army Medical University), Chongqing 400038, China. Electronic address:

It remains a great challenge for targeted therapy of heart diseases. To achieve desirable heart targeting, we developed a polyphenol-assisted nanoprecipitation/self-assembly approach for facile engineering of functional nanoparticles. Three different materials were employed as representative carriers, while gallic acid, catechin, epigallocatechin gallate, and tannic acid (TA) served as typical polyphenols with varied numbers of phenolic hydroxyl groups. By optimizing different parameters, such as polyphenol types and the weight ratio of carrier materials and polyphenols, well-defined nanoparticles with excellent physicochemical properties can be easily prepared. Regardless of various carrier materials, TA-derived nanoparticles showed potent reactive oxygen species-scavenging activity, especially nanoparticles produced from a cyclodextrin-derived bioactive material (TPCD). By internalization into cardiomyocytes, TPCD/TA nanoparticles (defined as TPTN) effectively protected cells from hypoxic-ischemic injury. After intravenous injection, TPTN considerably accumulated in the injured heart in two murine models of ventricular fibrillation cardiac arrest in rats and myocardial hypertrophy in mice. Correspondingly, intravenously delivered TPTN afforded excellent therapeutic effects in both heart diseases. Preliminary experiments also revealed good safety of TPTN. These results substantiated that TPTN is a promising nanotherapy for targeted treatment of heart diseases, while polyphenol-assisted self-assembly is a facile but robust strategy to develop heart-targeting delivery systems.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120952DOI Listing
August 2021

Evaluation of the application of TSH receptor stimulating autoantibodies and the optimization of detection strategy in Graves' disease.

Clin Chim Acta 2021 Oct 16;521:34-39. Epub 2021 Jun 16.

Department of Clinical Laboratory, Shanghai Tong Ren Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China. Electronic address:

Background: We evaluated the use of thyroid stimulating immunoglobulin (TSI) assay to optimize the detection strategy for Graves' disease.

Methods: Five hundred and forty-four well characterized serum samples from the Clinical Laboratory of Shanghai Tongren Hospital were collected from August 2019 to April 2020. The serum samples were obtained from 52 untreated GD patients, 155 treated GD patients, 83 patients with Hashimoto's thyroiditis, 70 patients with thyroid nodules, 83 patients with thyroid cancer, and 101 healthy subjects. All samples were evaluated by both TSI assay and TSH receptor autoantibodies (TRAb) assay. Moreover, 23 patients without a distinct thyroid disease diagnosis at the first visit were monitored for 6 months to make a final diagnosis.

Results: The clinical sensitivity of the TSI and TRAb assays was 98.10% and 94.20% respectively, while the clinical specificity was 92.30% and 96.70% respectively. ROC plot analysis based on sera of UT-GD (newly diagnosed GD patients) revealed an area under the curve (AUC) of 0.974 for the TSI assay. The best cutoff value was 0.58 IU/l (98.0% of sensitivity, 92.8% of specificity). The AUC for the TRAb assay was 0.961. Furthermore, combining TSI and TRAb results, the area under the curve was 0.981. In a pilot study of 23 patients with an uncertain initial diagnosis, the follow-up results showed the clinical diagnosis of 22 out of 23 cases were resolved in agreement with the results obtained by the TSI assay, and one case matched the result obtained by TRAb assay.

Conclusion: The TSI assay presents very promising analytical characteristics and could be adopted in clinical practice to improve GD diagnosis. The TSI assay might be better than TRAb assay in initial differential diagnosis of GD from other thyroid diseases.
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http://dx.doi.org/10.1016/j.cca.2021.06.017DOI Listing
October 2021

Ferroelectric Self-Polarization Controlled Magnetic Stratification and Magnetic Coupling in Ultrathin LaSrMnO Films.

ACS Appl Mater Interfaces 2021 Jun 17;13(25):30137-30145. Epub 2021 Jun 17.

Department of Materials Science & Engineering, National University of Singapore, Singapore 117575, Singapore.

Multiferroic oxide heterostructures consisting of ferromagnetic and ferroelectric components hold the promise for nonvolatile magnetic control via ferroelectric polarization, advantageous for the low-dissipation spintronics. Modern understanding of the magnetoelectric coupling in these systems involves structural, orbital, and magnetic reconstructions at interfaces. Previous works have long proposed polarization-dependent interfacial magnetic structures; however, direct evidence is still missing, which requires advanced characterization tools with near-atomic-scale spatial resolutions. Here, extensive polarized neutron reflectometry (PNR) studies have determined the magnetic depth profiles of PbZrTiO/LaSrMnO (PZT/LSMO) bilayers with opposite self-polarizations. When the LSMO is 2-3 nm thick, the bilayers show two magnetic transitions on cooling. However, temperature-dependent magnetization is different below the lower-temperature transition for opposite polarizations. PNR finds that the LSMO splits into two magnetic sublayers, but the inter-sublayer magnetic couplings are of opposite signs for the two polarizations. Near-edge X-ray absorption spectroscopy further shows contrasts in both the Mn valences and the Mn-O bond anisotropy between the two polarizations. This work completes the puzzle for the magnetoelectric coupling model at the PZT/LSMO interface, showing a synergic interplay among multiple degrees of freedom toward emergent functionalities at complex oxide interfaces.
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http://dx.doi.org/10.1021/acsami.1c02300DOI Listing
June 2021

Defect Engineering of Nanoscale Hf-Based Metal-Organic Frameworks for Highly Efficient Iodine Capture.

Inorg Chem 2021 Jul 16;60(13):9848-9856. Epub 2021 Jun 16.

State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun, Jilin 130022, P. R. China.

With the rapid development of the nuclear industry, how to deal with radioactive iodine waste in a timely and effective manner has become an important issue to be solved urgently. Herein, the defect-engineering strategy has been applied to develop a metal-organic framework (MOF)-based solid adsorbent by using the classical UiO-type Hf-UiO-66 as an example. After simple acid treatment, the produced defect-containing Hf-UiO-66 (DHUN) not only retains its topological structure, high crystallization, and regular shape but also shows a great increase in the Brunauer-Emmett-Teller value and pore size in comparison with the original Hf-UiO (HUN). These formed defects within DHUN have been demonstrated to be important for the great enhancement of the iodine capture and following application in computed tomography imaging . This present work gives a new insight into the control and formation of defect sites, and this simple and efficient defect-engineering strategy also shows great promise for the development of novel solid adsorbents and other functional MOF materials.
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http://dx.doi.org/10.1021/acs.inorgchem.1c01120DOI Listing
July 2021

Cell cycle exit and neuronal differentiation 1-engineered embryonic neural stem cells enhance neuronal differentiation and neurobehavioral recovery after experimental traumatic brain injury.

Neural Regen Res 2022 Jan;17(1):130-136

Department of Neurosurgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Our previous study showed that cell cycle exit and neuronal differentiation 1 (CEND1) may participate in neural stem cell cycle exit and oriented differentiation. However, whether CEND1-transfected neural stem cells can improve the prognosis of traumatic brain injury remained unclear. In this study, we performed quantitative proteomic analysis and found that after traumatic brain injury, CEND1 expression was downregulated in mouse brain tissue. Three days after traumatic brain injury, we transplanted CEND1-transfected neural stem cells into the area surrounding the injury site. We found that at 5 weeks after traumatic brain injury, transplantation of CEND1-transfected neural stem cells markedly alleviated brain atrophy and greatly improved neurological function. In vivo and in vitro results indicate that CEND1 overexpression inhibited the proliferation of neural stem cells, but significantly promoted their neuronal differentiation. Additionally, CEND1 overexpression reduced protein levels of Notch1 and cyclin D1, but increased levels of p21 in CEND1-transfected neural stem cells. Treatment with CEND1-transfected neural stem cells was superior to similar treatment without CEND1 transfection. These findings suggest that transplantation of CEND1-transfected neural stem cells is a promising cell therapy for traumatic brain injury. This study was approved by the Animal Ethics Committee of the School of Biomedical Engineering of Shanghai Jiao Tong University, China (approval No. 2016034) on November 25, 2016.
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http://dx.doi.org/10.4103/1673-5374.314316DOI Listing
January 2022

Tension-compression asymmetry in amorphous silicon.

Nat Mater 2021 May 31. Epub 2021 May 31.

Center for Advancing Materials Performance from the Nanoscale and Hysitron Applied Research Center in China, State Key Laboratory for Mechanical Behavior of Materials, Xi'an Jiaotong University, Xi'an, China.

Hard and brittle materials usually exhibit a much lower strength when loaded in tension than in compression. However, this common-sense behaviour may not be intrinsic to these materials, but arises from their higher flaw sensitivity to tensile loading. Here, we demonstrate a reversed and unusually pronounced tension-compression asymmetry (tensile strength exceeds compressive strength by a large margin) in submicrometre-sized samples of isotropic amorphous silicon. The abnormal asymmetry in the yield strength and anelasticity originates from the reduction in shear modulus and the densification of the shear-activated configuration under compression, altering the magnitude of the activation energy barrier for elementary shear events in amorphous Si. In situ coupled electrical tests corroborate that compressive strains indeed cause increased atomic coordination (metallization) by transforming some local structures from sp-bonded semiconducting motifs to more metallic-like sites, lending credence to the mechanism we propose. This finding opens up an unexplored regime of intrinsic tension-compression asymmetry in materials.
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http://dx.doi.org/10.1038/s41563-021-01017-zDOI Listing
May 2021

Wavelength-Tunable, Long Lifetime, and Biocompatible Luminescent Nanoparticles Based on a Vitamin E-Derived Material for Inflammation and Tumor Imaging.

Small 2021 06 24;17(25):e2100045. Epub 2021 May 24.

Department of Pharmaceutics, College of Pharmacy, Third Military Medical University (Army Medical University), Chongqing, 400038, China.

Luminescence imaging is one of the most effective noninvasive strategies for detection and stratification of inflammation and oxidative stress that are closely related to the pathogenesis of numerous acute and chronic diseases. Herein biocompatible nanoparticles based on a peroxalate ester derived from vitamin E (defined as OVE) are developed. In combination with different fluorophores, OVE can generate luminescence systems with emission wavelengths varying from blue to the near-infrared light in its native and nanoparticle forms, in the presence of hydrogen peroxide (H O ). The OVE-based nanoprobes exhibit high luminescence signals with extremely long lifetime, upon triggering by inflammatory conditions with abnormally elevated H O . Activated neutrophils and macrophages can be illuminated by this type of luminescent nanoprobes, with luminescence intensities positively correlated with inflammatory cell counts. In mouse models of peritonitis, alcoholic liver injury, drug-induced acute liver injury, and acute lung injury, the developed luminescence nanoprobes enable precision imaging of inflammation and disease progression. Moreover, tumors expressing a high level of H O can be shined. Importantly, the OVE-based nanoplatform shows excellent in vitro and in vivo biocompatibility.
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http://dx.doi.org/10.1002/smll.202100045DOI Listing
June 2021

Orphan drugs in different countries and development of new drugs to treat biliary tract cancer.

Intractable Rare Dis Res 2021 May;10(2):146-147

Department of Oncology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.

Biliary tract cancer (BTC), which includes cholangiocarcinoma and gallbladder carcinoma, is a rare malignancy. Due to its low incidence, drugs treating these diseases are scarce, so they can be considered orphan drugs. The main treatment choice for BTC is chemotherapy with gemcitabine or cisplatin or combined use of both, but patients fail to significantly benefit from established chemotherapy. Advancements in immunotherapy and targeted therapy will shed light on ways to improve clinical outcomes for patients with BTC. In conjunction, more new drugs will come onto the market. This article compares the conditions for development of orphan drugs in different countries and it describes several types of new drugs that were recently approved to treat BTC.
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http://dx.doi.org/10.5582/irdr.2021.01038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8122311PMC
May 2021

Microlattice Metamaterials with Simultaneous Superior Acoustic and Mechanical Energy Absorption.

Small 2021 Jun 13;17(24):e2100336. Epub 2021 May 13.

Department of Mechanical Engineering, National University of Singapore, Singapore, 117575, Singapore.

The advent of 3D printing brought about the possibilities of microlattice metamaterials as advanced materials with the potentials to surpass the functionalities of traditional materials. Sound absorbing materials which are also tough and lightweight are of particular importance as practical engineering materials. There are however a lack of attempts on the study of metamaterials multifunctional for both purposes. Herein, we present four types of face-centered cubic based plate and truss microlattices as novel metamaterials with simultaneous excellent sound and mechanical energy absorption performance. High sound absorption coefficients nearing 1 and high specific energy absorption of 50.3 J g have been measured. Sound absorption mechanisms of microlattices are proposed to be based on a "cascading resonant cells theory", an extension of the Helmholtz resonance principle that we have conceptualized herein. Characteristics of absorption coefficients are found to be essentially geometry limited by the pore and cavity morphologies. The excellent mechanical properties in turn derive from both the approximate membrane stress state of the plate architecture and the excellent ductility and strength of the base material. Overall, this work presents a new concept on the specific structural design and materials selection for architectured metamaterials with dual sound and mechanical energy absorption capabilities.
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http://dx.doi.org/10.1002/smll.202100336DOI Listing
June 2021

The emerging roles of dual-specificity phosphatases and their specific characteristics in human cancer.

Biochim Biophys Acta Rev Cancer 2021 08 5;1876(1):188562. Epub 2021 May 5.

Breast and Thyroid Surgery, Southwest Hospital, Army Medical University, Chongqing 400038, China. Electronic address:

Reversible phosphorylation of proteins, controlled by kinases and phosphatases, is involved in various cellular processes. Dual-specificity phosphatases (DUSPs) can dephosphorylate phosphorylated serine, threonine and tyrosine residues. This family consists of 61 members, 44 of which have been identified in human, and these 44 members are classified into six subgroups, the phosphatase and tensin homolog (PTEN) protein phosphatases (PTENs), mitogen-activated protein kinase phosphatases (MKPs), atypical DUSPs, cell division cycle 14 (CDC14) phosphatases (CDC14s), slingshot protein phosphatases (SSHs), and phosphatases of the regenerating liver (PRLs). Growing evidence has revealed dysregulation of DUSPs as one of the common phenomenons and highlighted their key roles in human cancers. Furthermore, their differential expression may be a potential biomarker for tumor prognosis. Despite this, there are still many unstudied members of DUSPs need to further explore their precise roles and mechanism in cancers. Most importantly, the systematic review is very limited on the functional/mechanistic characteristics and clinical application of DUSPs at present. In this review, the structures, functions and underlying mechanisms of DUSPs are systematically reviewed, and the molecular and functional characteristics of DUSPs in different tumor types according to the current researches are summarized. In addition, the potential roles of the unstudied members and the possible different mechanisms of DUSPs in cancer are discussed and classified based on homology alignment and structural domain analyses. Moreover, the specific characteristics of their expression and prognosis are further determined in more than 30 types of human cancers by using the online databases. Finally, their potential application in precise diagnosis, prognosis and treatment of different types of cancers, and the main possible problems for the clinical application at present are prospected.
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http://dx.doi.org/10.1016/j.bbcan.2021.188562DOI Listing
August 2021

Fabrication of 3D-Printed Ceramic Structures for Portable Solar Desalination Devices.

ACS Appl Mater Interfaces 2021 May 6;13(19):23220-23229. Epub 2021 May 6.

Department of Materials Science and Engineering, Faculty of Engineering, National University of Singapore, 9 Engineering Drive 1, Block EA, Singapore 117575, Singapore.

This paper proposes the fabrication process of the first fully 3D-printed ceramic core structures for portable solar desalination devices optimized to tackle water scarcity from an energy and sustainability perspective. Robocasting, a 3D printing technique, is utilized to fabricate a fully ceramic structure of an integrated solar absorber/thermal insulator/water transporter based on the two-layered structure of modified graphene on silica ([email protected]) and the porous silica structure. Robocasting has demonstrated its flexibility in tailoring structural designs, combining nanopores and microchannels that exhibit uniform water transport delivery and thermal insulation. This portable device can be used immediately to collect fresh drinking water without an additional setup. It possesses a water evaporation rate of 2.4 kg m h with a drinking water production capacity of 0.5 L m h. This novel device has shown excellent ion rejection ability, with the collected water meeting the World Health Organization (WHO) drinking water standards.
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http://dx.doi.org/10.1021/acsami.1c04209DOI Listing
May 2021

Homeobox-A13 acts as a functional prognostic and diagnostic biomarker via regulating P53 and Wnt signaling pathways in lung cancer.

Cancer Biomark 2021 ;31(3):239-254

Department of Oncology, Southwest Hospital, Army Medical University, Chongqing, China.

Background: The prognosis of lung cancer patients is poor without useful prognostic and diagnostic biomarker. To search for novel prognostic and diagnostic markers, we previously found homeobox-A13 (HOXA13) as a promising candidate in lung cancer.

Objective: To determine the precisely clinical feature, prognostic and diagnostic value, possible role and mechanism of HOXA13.

Methods: Gene-expression was explored by real-time quantitative-PCR, western-blot and tissue-microarray. The associations were analyzed by Chi-square test, Kaplan-Meier and Cox-regression. The roles and mechanisms were evaluated by MTS, EdU, transwell, xenograft tumor and luciferase-reporter assays.

Results: HOXA13 expression is increased in tumors, and correlated with age of patients. HOXA13 expression is associated with unfavorable overall survival and relapse-free survival of patients in four cohorts. Interestingly, HOXA13 has different prognostic significance in adenocarcinoma (ADC) and squamous-cell carcinoma (SCC), and is a sex- and smoke-related prognostic factor only in ADC. Importantly, HOXA13 can serve as a diagnostic biomarker for lung cancer, especially for SCC. HOXA13 can promote cancer-cell proliferation, migration and invasion in vitro, and facilitate tumorigenicity and tumor metastasis in vivo. HOXA13 acts the oncogenic roles on tumor growth and metastasis by regulating P53 and Wnt/β-catenin signaling activities in lung cancer.

Conclusions: HOXA13 is a new prognostic and diagnostic biomarker associated with P53 and Wnt/β-catenin signaling pathways.
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http://dx.doi.org/10.3233/CBM-200540DOI Listing
January 2021

Vaginal drug delivery approaches for localized management of cervical cancer.

Adv Drug Deliv Rev 2021 07 20;174:114-126. Epub 2021 Apr 20.

State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, PR China. Electronic address:

Cervical cancer or cervical intraepithelial neoplasia (CIN) remain a major public health problem among women globally. Traditional methods such as surgery are often associated with possible complications which may impact future pregnancies and childbirth especially for young female patients. Vagina with a high contact surface is a suitable route for the local and systemic delivery of drugs but its abundant mucus in continuous exchange presents a barrier for the popularization of conventional vaginal formulations including suppositories, gel, patch, creams and so on. So the development of new pharmaceutical forms based on nanotechnology became appealing owing to its several advantages such as mucosa penetration, bioadhesion, controlled drug release, and decreased adverse effects. This review provided an overview of the development of topical treatment of cervical cancer or CIN through vaginal drug delivery ranging from conventional vaginal formulations to new nanocarriers to the newly developed phototherapy and gene therapy, analyzing the problems faced by current methods used, and advising the developing trend in future. The methods of establishing preclinical animal model are also discussed.
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http://dx.doi.org/10.1016/j.addr.2021.04.009DOI Listing
July 2021
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