Publications by authors named "Yuqing Li"

291 Publications

ASXL1 promotes adrenocortical carcinoma and is associated with chemoresistance to EDP regimen.

Aging (Albany NY) 2021 Sep 18;13(undefined). Epub 2021 Sep 18.

Department of Urology, Fourth Affiliated Hospital of China Medical University, Shenyang 100032, Liaoning Province, P.R. China.

Adrenocortical carcinoma (ACC) is a rare but aggressive disease that lacks definitive treatment. We aim to evaluate role of ASXL1 in ACC and exploit its therapeutic merits therein. We performed reproduction of datasets of the Cancer Genome Atlas (TCGA), GDSC (Genomics of Drug Sensitivity in Cancer) and Human Protein Atlas using platforms of cBioPortal, UALCAN, NET-GE, GSEA and GEPIA. Validation in ACC was performed in tissue, and using the NCI-H295R and SW-13 cells. ASXL1 was gained in over 50% of ACC cases with its mRNA overexpressed in DNA gained cases. ASXL1 overexpression was associated with recurrence and worsened prognosis in ACC. ASXL1 gain was associated with resistance to etoposide, doxorubicin and cisplatin (EDP). ASXL1 expression was positively correlated with FSCN1 expression. Targeting ASXL1 significantly impaired fitness of ACC cells, which could be in part rescued by FSCN1 overexpression. Targeting FSCN1 however could not rescue resistance to EDP induced by ASXL1 overexpression. Targeting ASXL1 sensitized ACC cells to EDP regimen but constitutive ASXL3 overexpression in SW-13 cells could induce resistance upon prolonged treatment. Functional gain of ASXL1 was common in ACC and exerted pro-tumorigenic and chemoresistance role. Targeting ASXL1 hold promise to ACC treatment.
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http://dx.doi.org/10.18632/aging.203534DOI Listing
September 2021

Dendritic CsSnI for Efficient and Flexible Near-Infrared Perovskite Light-Emitting Diodes.

Adv Mater 2021 Sep 16:e2104414. Epub 2021 Sep 16.

Xiamen Key Laboratory of Optoelectronic Materials and Advanced Manufacturing, Institute of Luminescent Materials and Information Displays, College of Materials Science and Engineering, Huaqiao University, Xiamen, 361021, China.

All-inorganic and lead-free CsSnI is emerging as one of the most promising candidates for near-infrared perovskite light-emitting diodes (NIR Pero-LEDs), which find practical applications including facial recognition, biomedical apparatus, night vision camera, and Light Fidelity. However, in the CsSnI -based Pero-LEDs, the holes injection is significantly higher than that of electrons, resulting in unbalanced charge injection, undesired exciton dissipation, and poor device performance. Herein, it is proposed to manage charge injection and recombination behavior by tuning the interface area of perovskite and charge-transporter. A dendritic CsSnI structure is prepared on the hole-transporter, only making a bottom contact with the hole-transporter and exposing all other available crystal surfaces to the electron-transporter. In other words, the interface area of perovskite/electron-transporter is significantly higher than that of perovskite/hole-transporter. Moreover, the embedding interface of perovskite/electron-transporter can spatially confine holes and electrons, increasing the radiation recombination. By taking advantage of the dendritic structure, efficient lead-free NIR Pero-LEDs are achieved with a record external quantum efficiency (EQE) of 5.4%. More importantly, the dendritic structure shows great superiorities in flexible devices, for there is almost no morphology change after 2000-cycles of bends, and the fabricated Pero-LEDs can keep 93.4% of initial EQEs after 50-cycles of bends.
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http://dx.doi.org/10.1002/adma.202104414DOI Listing
September 2021

Expression Analysis of MaTGA8 Transcription Factor in Banana and Its Defence Functional Analysis by Overexpression in Arabidopsis.

Int J Mol Sci 2021 Aug 28;22(17). Epub 2021 Aug 28.

Institute of Horticulture Science and Engineering, Huaqiao University, Xiamen 361021, China.

TGA transcription factor is a member of the D subfamily of the basic region-leucine zippers (bZIP) family. It is a type of transcription factor that was first identified in plants and is the main regulator in plant development and physiological processes, including morphogenesis and seed formation in response to abiotic and biotic stress and maintaining plant growth. The present study examined the sequence of the transcription factor, the sequence of which belonged to subfamily D of the bZIP and had multiple cis-acting elements such as the G-box, TCA-element, TGACG-element, and P-box. Quantitative real time polymerase chain reaction (qRT-PCR) analyses showed that was significantly down-regulated by the soil-borne fungus f. sp. race 4 (Foc TR4). Under the induction of salicylic acid (SA), was down-regulated, while different members of the family responded significantly differently. Among them, and showed an overall upward trend, and the expression level of , and was higher than other members. is a nuclear-localized transcription factor through strong interaction with or weaker interaction with , and it is implied that the gene can be activated. In addition, the transgenic has obvious disease resistance and higher chlorophyll content than the wild-type with the infection of Foc TR4. These results indicate that may enhance the resistance of bananas to Foc TR4 by interacting with or . This study provides a basis for further research on the application of banana TGA transcription factors in Foc TR4 stress and disease resistance and molecular breeding programs.
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http://dx.doi.org/10.3390/ijms22179344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430518PMC
August 2021

A Novel Framework for Anomaly Detection for Satellite Momentum Wheel Based on Optimized SVM and Huffman-Multi-Scale Entropy.

Entropy (Basel) 2021 Aug 17;23(8). Epub 2021 Aug 17.

Deep Space Exploration Research Center, Harbin Institute of Technology, Harbin 150080, China.

The health status of the momentum wheel is vital for a satellite. Recently, research on anomaly detection for satellites has become more and more extensive. Previous research mostly required simulation models for key components. However, the physical models are difficult to construct, and the simulation data does not match the telemetry data in engineering applications. To overcome the above problem, this paper proposes a new anomaly detection framework based on real telemetry data. First, the time-domain and frequency-domain features of the preprocessed telemetry signal are calculated, and the effective features are selected through evaluation. Second, a new Huffman-multi-scale entropy (HMSE) system is proposed, which can effectively improve the discrimination between different data types. Third, this paper adopts a multi-class SVM model based on the directed acyclic graph (DAG) principle and proposes an improved adaptive particle swarm optimization (APSO) method to train the SVM model. The proposed method is applied to anomaly detection for satellite momentum wheel voltage telemetry data. The recognition accuracy and detection rate of the method proposed in this paper can reach 99.60% and 99.87%. Compared with other methods, the proposed method can effectively improve the recognition accuracy and detection rate, and it can also effectively reduce the false alarm rate and the missed alarm rate.
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http://dx.doi.org/10.3390/e23081062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8391409PMC
August 2021

Transcriptional Profiling Reveals the Importance of RcrR in the Regulation of Multiple Sugar Transportation and Biofilm Formation in Streptococcus mutans.

mSystems 2021 Aug 24;6(4):e0078821. Epub 2021 Aug 24.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan Universitygrid.13291.38, Chengdu, China.

The ability of Streptococcus mutans to survive and cause dental caries is dependent on its ability to metabolize various carbohydrates, accompanied by extracellular polysaccharide synthesis and biofilm formation. Here, the role of an competence-related regulator (RcrR) in the regulation of multiple sugar transportation and biofilm formation is reported. The deletion of the gene in S. mutans caused delayed growth, decreased biofilm formation ability, and affected the expression level of its multiple sugar transportation-related genes. Transcriptional profiling revealed 17 differentially expressed genes in the mutant. Five were downregulated and clustered with the sugar phosphotransferase (PTS) systems (mannitol- and trehalose-specific PTS systems). The conserved sites bound by the promoter were then determined by electrophoretic mobility shift assays (EMSAs) and DNase I footprinting assays. Furthermore, a potential binding motif in the promoters of the two PTS operons was predicted using MEME Suite 5.1.1. RcrR could bind to the promoter regions of the two operons , and the sugar transporter-related genes of the two operons were upregulated in an -overexpressing strain. In addition, when RcrR-binding sites were deleted, the growth rates and final yield of S. mutans were significantly decreased in tryptone-vitamin (TV) medium supplemented with different sugars, but not in absolute TV medium. These results revealed that RcrR acted as a transcription activator to regulate the two PTS systems, accompanied by multiple sugar transportation and biofilm formation. Collectively, these results indicate that RcrR is a critical transcription factor in S. mutans that regulates bacterial growth, biofilm formation, and multiple sugar transportation. The human oral cavity is a constantly changing environment. Tooth decay is a commonly prevalent chronic disease mainly caused by the cariogenic bacterium Streptococcus mutans. S. mutans is an oral pathogen that metabolizes various carbohydrates into extracellular polysaccharides (EPSs), biofilm, and tooth-destroying lactic acid. The host diet strongly influences the availability of multiple carbohydrates. Here, we showed that the RcrR transcription regulator plays a significant role in the regulation of biofilm formation and multiple sugar transportation. Further systematic evaluation of how RcrR regulates the transportation of various sugars and biofilm formation was also conducted. Notably, this study decrypts the physiological functions of RcrR as a potential target for the better prevention of dental caries.
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http://dx.doi.org/10.1128/mSystems.00788-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8407328PMC
August 2021

Preparing Selective Nanozymes by Molecular Imprinting.

Methods Mol Biol 2021 ;2359:223-232

Department of Chemistry, Waterloo Institute for Nanotechnology, University of Waterloo, Waterloo, ON, Canada.

Recently, many nanomaterials such as FeO, CeO, and gold nanoparticles have been reported to have enzyme-like activities and they are called nanozymes. Although these nanozymes have oxidase or peroxidase-like activities, they can catalyze the oxidation of many substrates and thus lack the specificity expected for enzymes. The selectivity of nanozymes can be significantly enhanced up to 100-fold by coating them with a molecularly imprinted polymer (MIP) layer. Since MIP creates specific binding pockets for the imprinted substrate, the imprinted molecules can be enriched, selectively access the catalytic core, and be oxidized, while other substrates are blocked from accessing the nanozyme surface. In this chapter, the detailed protocol for the preparation of the MIP-coated FeO peroxidase-mimicking nanozymes is described. In addition, some procedures needing special attention are described in detail, which will facilitate the applications of MIP-coated nanozymes in analytical, biomedical, and environmental fields.
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http://dx.doi.org/10.1007/978-1-0716-1629-1_19DOI Listing
January 2021

The Adc regulon mediates zinc homeostasis in Streptococcus mutans.

Mol Oral Microbiol 2021 10 13;36(5):278-290. Epub 2021 Aug 13.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Zinc (Zn ) is an essential divalent trace metal for living cells. Intracellular zinc homeostasis is critical to the survival and virulence of bacteria. Thus, the frequent fluctuations of salivary zinc, caused by the low physiological level and the frequent exogenous zinc introduction, present a serious challenge for bacteria colonizing the oral cavity. However, the regulation strategies to keep intracellular Zn homeostasis in Streptococcus mutans, an important causative pathogen of dental caries, are unknown. Because zinc uptake is primarily mediated by an ATP-binding ABC transporter AdcABC in Streptococcus strains, we examined the function of AdcABC and transcription factor AdcR in S. mutans in this study. The results demonstrated that deletion of either adcA or adcCB gene impaired the growth but enhanced the extracellular polymeric matrix production in S. mutans, both of which could be relieved after excessive Zn supplementation. Using RNA sequencing analysis, quantitative reverse transcription polymerase chain reaction examination, LacZ-reporter studies, and electrophoretic mobility shift assay, we showed that a MarR (multiple antibiotic resistance regulator) family transcription factor, AdcR, negatively regulates the expression of the genes adcR, adcC, adcB, and adcA by acting on the adcRCB and adcA promoters in response to Zn concentration in their environmental niches. The deletion of adcR increases the sensitivity of S. mutans to excessive Zn supply. Taken together, our findings suggest that Adc regulon, which consists of a Zn uptake transporter AdcCBA and a Zn -responsive repressor AdcR, plays a prominent role in the maintenance of intracellular zinc homeostasis of S. mutans.
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http://dx.doi.org/10.1111/omi.12350DOI Listing
October 2021

Genome-wide association study of pancreatic fat: The Multiethnic Cohort Adiposity Phenotype Study.

PLoS One 2021 30;16(7):e0249615. Epub 2021 Jul 30.

University of Hawaii Cancer Center, University of Hawaii at Mānoa, Honolulu, Hawaii, United States of America.

Several studies have found associations between higher pancreatic fat content and adverse health outcomes, such as diabetes and the metabolic syndrome, but investigations into the genetic contributions to pancreatic fat are limited. This genome-wide association study, comprised of 804 participants with MRI-assessed pancreatic fat measurements, was conducted in the ethnically diverse Multiethnic Cohort-Adiposity Phenotype Study (MEC-APS). Two genetic variants reaching genome-wide significance, rs73449607 on chromosome 13q21.2 (Beta = -0.67, P = 4.50x10-8) and rs7996760 on chromosome 6q14 (Beta = -0.90, P = 4.91x10-8) were associated with percent pancreatic fat on the log scale. Rs73449607 was most common in the African American population (13%) and rs79967607 was most common in the European American population (6%). Rs73449607 was also associated with lower risk of type 2 diabetes (OR = 0.95, 95% CI = 0.89-1.00, P = 0.047) in the Population Architecture Genomics and Epidemiology (PAGE) Study and the DIAbetes Genetics Replication and Meta-analysis (DIAGRAM), which included substantial numbers of non-European ancestry participants (53,102 cases and 193,679 controls). Rs73449607 is located in an intergenic region between GSX1 and PLUTO, and rs79967607 is in intron 1 of EPM2A. PLUTO, a lncRNA, regulates transcription of an adjacent gene, PDX1, that controls beta-cell function in the mature pancreas, and EPM2A encodes the protein laforin, which plays a critical role in regulating glycogen production. If validated, these variants may suggest a genetic component for pancreatic fat and a common etiologic link between pancreatic fat and type 2 diabetes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249615PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323875PMC
July 2021

Directional Magnetization Reversal Enables Ultrahigh Energy Density in Gradient Nanostructures.

Adv Mater 2021 Sep 26;33(36):e2102800. Epub 2021 Jul 26.

State Key Laboratory of Metastable Materials Science and Technology, Yanshan University, Qinhuangdao, 066004, China.

High-performance ferromagnetic materials are essential for energy conversion and electronic devices. However, the random and nonuniform magnetization reversal in ferromagnetics limits their performance that can be achieved. Here, through both micromagnetism simulations and experiments, a directional magnetization reversal that initiates first from large grains toward smaller ones is discovered by engineering Nd Fe B/α-Fe gradient nanostructures. Such directional magnetization reversal enables a rare combination of high magnetization and large coercivity, thus leading to a record-high energy density (26 MG Oe) for isotropic permanent magnetic materials, which is ≈50% higher than that of its gradient-free counterpart. The unusual magnetization reversal originates from an ordered arrangement of grain sizes in the gradient material, where the large grains have a lower reversal field than that of the smaller ones. These findings open up new opportunities for developing high-performance magnetic materials.
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http://dx.doi.org/10.1002/adma.202102800DOI Listing
September 2021

Pectic Oligogalacturonide Facilitates the Synthesis and Activation of Adiponectin to Improve Hepatic Lipid Oxidation.

Mol Nutr Food Res 2021 Jul 15:e2100167. Epub 2021 Jul 15.

College of Food Science, Shenyang Agricultural University, 120 Dongling Road, Shenhe District, Shenyang, 110866, China.

Scope: Adiponectin (ADPN), a kind of adipokines, plays an important role in the regulation of lipid metabolism. The objective of this study is focused on the ADPN to investigate the functional mechanisms of pectin oligosaccharide (POS) from hawthorn fruit in the improvement of hepatic fatty acid oxidation.

Method And Results: High-fat fed mice are used in this experiment. POS is administrated with the doses of 0.25, 0.75, and 1.5 g kg diet, respectively. The results demonstrate that gene and protein expressions of ADPN synthesis regulators involved in PKA/ERK/CREB and C/EBPα/PPARγ pathways are upregulated by POS administration. POS also activates the AdiopR1/AMPKα/PGC1 and AdipoR2/PPARα signaling pathways to improve the fatty acid oxidation in the liver, which is further accelerated by the enhancement of mitochondrial functions.

Conclusion: POS can act as an ADPN activator to improve lipid metabolism, leading it to the applications of biomedical and functional foods for ameliorating chronic liver diseases resulted from a high-energy diet.
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http://dx.doi.org/10.1002/mnfr.202100167DOI Listing
July 2021

The Effects of Nonnutritive Sweeteners on the Cariogenic Potential of Oral Microbiome.

Biomed Res Int 2021 24;2021:9967035. Epub 2021 Jun 24.

State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.

Nonnutritive sweeteners (NNSs) are sugar substitutes widely used to reduce the negative health effects of excessive sugar consumption. Dental caries, one of the most prevalent chronic diseases globally, results from a pathogenic biofilm with microecological imbalance and frequent exposure to sugars. Some research has shown that certain NNSs possess less cariogenic potential than sucrose, indicating their putative effect on oral microbiome. To uncover the alterations of acidogenic pathogens and alkali-generating commensals, as well as the biofilm cariogenic potential under the influence of NNSs, we selected four common NNSs (acesulfame-K, aspartame, saccharin, and sucralose) and established single-, dual-, and multispecies culture model to assess their effects on () and/or () compared to sucrose with the same sweetness. The results showed that NNSs significantly suppressed the planktonic growth, acid production, and biofilm formation of or compared with sucrose in single-species cultures. Additionally, decreased / ratio, less EPS generation, and higher pH value were observed in dual-species and saliva-derived multispecies biofilms with supplementary NNSs. Collectively, this study demonstrates that NNSs inhibit the cariogenic potential of biofilms by maintaining microbial equilibrium, thus having a promising prospect as anticaries agents.
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http://dx.doi.org/10.1155/2021/9967035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253641PMC
June 2021

CXC chemokines and their receptors in black rockfish (Sebastes schlegelii): Characterization, evolution analyses, and expression pattern after Aeromonas salmonicida infection.

Int J Biol Macromol 2021 Sep 7;186:109-124. Epub 2021 Jul 7.

School of Marine Science and Engineering, Qingdao Agricultural University, Qingdao 266109, China. Electronic address:

Chemokines are crucial regulators of cell mobilization for development, homeostasis, and immunity. Chemokines signal through binding to chemokine receptors, a superfamily of seven-transmembrane domain G-coupled receptors. In the present study, seventeen CXC chemokine ligands (SsCXCLs) and nine CXC chemokine receptors (SsCXCRs) were systematically identified from Sebastes schlegelii genome. Phylogeny, synteny, and evolutionary analyses were performed to annotate these genes, indicating that the tandem duplications (CXCL8, CXCL11, CXCL32, CXCR2, and CXCR3), the whole genome duplications (CXCL8, CXCL12, CXCL18, and CXCR4), and the teleost-specific members (CXCL18, CXCL19, and CXCL32) led to the expansion of SsCXCLs and SsCXCRs. In addition, SsCXCLs and SsCXCRs were ubiquitously expressed in nine examined healthy tissues, with high expression levels observed in head kidney, liver, gill and spleen. Moreover, most SsCXCLs and SsCXCRs were significantly differentially expressed in head kidney, liver, and gill after Aeromonas salmonicida infection, and exhibited tissue-specific and time-dependent manner. Finally, protein-protein interaction network (PPI) analysis indicated that SsCXCLs and SsCXCRs interacted with a few immune-related genes such as interleukins, cathepsins, CD genes, and TLRs, etc. These results should be valuable for comparative immunological studies and provide insights for further functional characterization of chemokines and receptors in teleost.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.07.014DOI Listing
September 2021

Systematic Pan-Cancer Population-Based Analysis Reveals the Incidence and Prognosis of Lung Metastases at Diagnosis.

J Oncol 2021 15;2021:9999968. Epub 2021 Jun 15.

Department of Pulmonary and Critical Care Medicine, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, No. 4, Kangle Road, Zhangjiagang City, Jiangsu Province, China.

Background: Metastasis is one of the most prevalent causes of death in cancer patients and the lungs are among the organs most commonly affected by metastasis. However, analysis of the incidence and prognosis of lung metastasis (LM) based on primary cancer sites is lacking.

Methods: We enrolled cancer patients with LM from the Surveillance, Epidemiology, and End Results (SEER) database. The risk factors for LM were determined using multivariate logistics regression. Forest plots were used to compare the impact of with LM versus without LM alone among different primary caner site subgroups.

Results: Among 1,525,441 cases, 47,537 presented with LM at initial diagnosis. Multivariate logistics regression revealed that male sex, older age, later T/N stage, unmarried status, and lack of insurance were risk factors for LM. The incidence of LM was 11.91% in bone cancer and 11.19% in pancreatic cancer. In terms of the distribution of primary cancers, 19.22% of LMs originated from the colon and rectum, with 11.63% from the kidneys. The median survival for LM cases was 6 months, with the best survival in testicular cancer (19 months) and bone cancer (12 months). Patients with LM had higher hazard ratio (HR) for mortality compared to those without LM, except for those with primary cancer in the brain (=0.09). We stratified patients by primary cancer site, and subgroup analyses showed that LM had a significant negative impact on survival. The most significant was in thyroid cancer (HR = 44.79), followed by melanoma (HR = 24.26), prostate (HR = 16.0), breast (HR = 13.46), endometrial (HR = 12.64), testicular (HR = 12.31), and kidney (HR = 11.33) cancer (all < 0.001).

Conclusion: Patients presenting with LM had higher HR for mortality compared to those without LM, except for those with brain tumor. Clinicians should pay more attention to the occurrence of LM, especially in patients with a significantly increased HR for mortality, such as those with thyroid cancer, melanoma, and prostate cancer.
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http://dx.doi.org/10.1155/2021/9999968DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221885PMC
June 2021

Reversal of motor-skill transfer impairment by trihexyphenidyl and reduction of dorsolateral striatal cholinergic interneurons in ΔGAG knock-in mice.

IBRO Neurosci Rep 2021 Dec 12;11:1-7. Epub 2021 Jun 12.

Norman Fixel Institute of Neurological Diseases, McKnight Brain Institute, and Department of Neurology, College of Medicine, University of Florida, Gainesville, FL 32610-0236, USA.

DYT-TOR1A or DYT1 early-onset generalized dystonia is an inherited movement disorder characterized by sustained muscle contractions causing twisting, repetitive movements, or abnormal postures. The majority of the DYT1 dystonia patients have a trinucleotide GAG deletion in . Trihexyphenidyl (THP), an antagonist for excitatory muscarinic acetylcholine receptor M1, is commonly used to treat dystonia. heterozygous ΔGAG knock-in (KI) mice, which have the corresponding mutation, exhibit impaired motor-skill transfer. Here, the effect of THP injection during the treadmill training period on the motor-skill transfer to the accelerated rotarod performance was examined. THP treatment reversed the motor-skill transfer impairment in KI mice. Immunohistochemistry showed that KI mice had a significant reduction of the dorsolateral striatal cholinergic interneurons. In contrast, Western blot analysis showed no significant alteration in the expression levels of the striatal enzymes and transporters involved in the acetylcholine metabolism. The results suggest a functional alteration of the cholinergic system underlying the impairment of motor-skill transfer and the pathogenesis of DYT1 dystonia. Training with THP in a motor task may improve another motor skill performance in DYT1 dystonia.
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http://dx.doi.org/10.1016/j.ibneur.2021.05.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215213PMC
December 2021

Cobalt induces neurodegenerative damages through Pin1 inactivation in mice and human neuroglioma cells.

J Hazard Mater 2021 10 12;419:126378. Epub 2021 Jun 12.

Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou 350122, China; Fujian Provincial Key Laboratory of Environmental Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou 350122, China; The Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou 350122, China. Electronic address:

Cobalt is a hazardous material that has harmful effects on neurotoxicity. Excessive exposure to cobalt or inactivation of the unique proline isomerase Pin1 contributes to age-dependent neurodegeneration. However, nothing is known about the role of Pin1 in cobalt-induced neurodegeneration. Here we find that out of several hazardous materials, only cobalt dose-dependently decreased Pin1 expression and alterations in its substrates, including cis and trans phosphorylated Tau in human neuronal cells, concomitant with neurotoxicity. Cobalt-induced neurotoxicity was aggravated by Pin1 genetic or chemical inhibition, but rescued by Pin1 upregulation. Furthermore, less than 4 μg/l of blood cobalt induced dose- and age-dependent Pin1 downregulation in murine brains, ensuing neurodegenerative changes. These defects were corroborated by changes in Pin1 substrates, including cis and trans phosphorylated Tau, amyloid precursor protein, β amyloid and GSK3β. Moreover, blood Pin1 was downregulated in human hip replacement patients with median blood cobalt level of 2.514 μg/l, which is significantly less than the safety threshold of 10 μg/l, suggesting an early role Pin1 played in neurodegenerative damages. Thus, Pin1 inactivation by cobalt contributes to age-dependent neurodegeneration, revealing that cobalt is a hazardous material triggering AD-like neurodegenerative damages.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126378DOI Listing
October 2021

Propofol ameliorates renal ischemia/reperfusion injury by enhancing macrophage M2 polarization through PPARγ/STAT3 signaling.

Aging (Albany NY) 2021 06 10;13(11):15511-15522. Epub 2021 Jun 10.

Department of Anesthesiology, Cangzhou Central Hospital, Cangzhou, Hebei, China.

Propofol (Pro) confers protection against renal ischemia/reperfusion (rI/R) injury through incompletely characterized mechanisms. Since Pro has shown net anti-inflammatory properties as part of its beneficial effects, we examined the potential role of Pro in the modulation of macrophage polarization status during both rI/R injury and exposure of cultured peritoneal macrophages (PMs) to hypoxia/reoxygenation (H/R). Rats were subjected to 45-min r/IR surgery or a sham procedure and administered PBS (vehicle) or Pro during the ischemia stage. Pro administration attenuated rI/R-induced kidney damage and renal TNF-α, IL-6, and CXCL-10 expression. Enhanced macrophage M2 polarization, evidenced by reduced iNOS and increased Arg1 and Mrc1 mRNA levels, was further detected after Pro treatment both in the kidney, after rI/R , and in H/R-treated PMs. Pro administration also repressed phosphorylated signal transducer and activator of transcription 1 (p-STAT1) and increased p-STAT3, p-STAT6, and peroxisome proliferator-activated receptor-γ (PPARγ) mRNA levels in H/R-exposed PMs. Importantly, siRNA-mediated PPARγ silencing repressed Pro-mediated STAT3 activation in PMs and restored proinflammatory cytokine levels and prevented macrophage M2 marker expression in both rI/R-treated rats and cultured PMs. These findings suggest that Pro confers renoprotection against rI/R by stimulating PPARγ/STAT3-dependent macrophage conversion to the M2 phenotype.
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http://dx.doi.org/10.18632/aging.203107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221315PMC
June 2021

The CC and CXC chemokine receptors in turbot (Scophthalmus maximus L.) and their response to Aeromonas salmonicida infection.

Dev Comp Immunol 2021 Oct 1;123:104155. Epub 2021 Jun 1.

School of Marine Science and Engineering, Qingdao Agricultural University, Qingdao, 266109, China. Electronic address:

Chemokines are crucial regulators of cell mobilization for development, homeostasis, and immunity. Chemokines signal through binding to chemokine receptors, a superfamily of seven-transmembrane domain G-coupled receptors. In the present study, eleven CC chemokine receptors (CCRs) and seven CXC chemokine receptors (CXCRs) were identified from turbot genome. Phylogenetic and syntenic analyses were performed to annotate these genes, indicating the closest relationship between the turbot chemokine receptors and their counterparts of Japanese flounders (Paralichthys olivaceus). Evolutionary analyses revealed that the tandem duplications of CCR8 and CXCR3, the whole genome duplications of CCR6, CCR9, CCR12, and CXCR4, and the teleost-specific CCR12 led to the expansion of turbot chemokine receptors. In addition, turbot chemokine receptors were ubiquitously expressed in nine examined healthy tissues, with high expression levels observed in spleen, gill, and head kidney. Moreover, most turbot chemokine receptors were significantly differentially expressed in spleen and gill after Aeromonas salmonicida infection, and exhibited general down-regulations at early time points and then gradually up-regulated. Finally, protein-protein interaction network (PPI) analyses indicated that chemokine receptors interacted with a few immune-related genes such as interleukins, Grk genes, CD genes, etc. These results should be valuable for comparative immunological studies and provide insights for further functional characterization of chemokine receptors in turbots.
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http://dx.doi.org/10.1016/j.dci.2021.104155DOI Listing
October 2021

Naa10p and IKKα interaction regulates EMT in oral squamous cell carcinoma via TGF-β1/Smad pathway.

J Cell Mol Med 2021 Jul 31;25(14):6760-6772. Epub 2021 May 31.

Key Laboratory of Xinjiang Endemic and Ethnic Disease, School of Medicine, Shihezi University, Shihezi, China.

Epithelial-mesenchymal transition (EMT) has been contributed to increase migration and invasion of cancer cells. However, the correlate of Naa10p and IKKα with EMT in oral squamous cell carcinoma (OSCC) is not yet fully understood. In our present study, we found N-α-acetyltransferase 10 protein (Naa10p) and IκB kinase α (IKKα) were abnormally abundant in oral squamous cell carcinoma (OSCC). Bioinformatic results indicate that the expression of Naa10p and IKKα is correlated with TGF-β1/Smad and EMT-related molecules. The Transwell migration, invasion, qRT-PCR and Western blot assay indicated that Naa10p repressed OSCC cell migration, invasion and EMT, whereas IKKα promoted TGF-β1-mediated OSCC cell migration, invasion and EMT. Mechanistically, Naa10p inhibited IKKα activation of Smad3 through the interaction with IKKα directly in OSCC cells after TGF-β1 stimulation. Notably, knockdown of Naa10p reversed the IKKα-induced change in the migration, invasion and EMT-related molecules in OSCC cells after TGF-β1 stimulation. These findings suggest that Naa10p interacted with IKKα mediates EMT in OSCC cells through TGF-β1/Smad, a novel pathway for preventing OSCC.
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http://dx.doi.org/10.1111/jcmm.16680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278082PMC
July 2021

Characterization of the direct pathway in Dyt1 ΔGAG heterozygous knock-in mice and dopamine receptor 1-expressing-cell-specific Dyt1 conditional knockout mice.

Behav Brain Res 2021 Aug 24;411:113381. Epub 2021 May 24.

Norman Fixel Institute for Neurological Diseases, McKnight Brain Institute, and Department of Neurology, College of Medicine, University of Florida, Gainesville, FL, 32610-0236, USA. Electronic address:

DYT1 dystonia is a movement disorder mainly caused by a trinucleotide deletion (ΔGAG) in DYT1 (TOR1A), coding for torsinA. DYT1 dystonia patients show trends of decreased striatal ligand-binding activities to dopamine receptors 1 (D1R) and 2 (D2R). Dyt1 ΔGAG knock-in (KI) mice, which have the corresponding ΔGAG deletion, similarly exhibit reduced striatal D1R and D2R-binding activities and their expression levels. While the consequences of D2R reduction have been well characterized, relatively little is known about the effect of D1R reduction. Here, locomotor responses to D1R and D2R antagonists were examined in Dyt1 KI mice. Dyt1 KI mice showed significantly less responsiveness to both D1R antagonist SCH 23390 and D2R antagonist raclopride. The electrophysiological recording indicated that Dyt1 KI mice showed a significantly increased paired-pulse ratio of the striatal D1R-expressing medium spiny neurons and altered miniature excitatory postsynaptic currents. To analyze the in vivo torsinA function in the D1R-expressing neurons further, Dyt1 conditional knockout (Dyt1 d1KO) mice in these neurons were generated. Dyt1 d1KO mice had decreased spontaneous locomotor activity and reduced numbers of slips in the beam-walking test. Dyt1 d1KO male mice showed abnormal gait. Dyt1 d1KO mice showed defective striatal D1R maturation. Moreover, the mutant striatal D1R-expressing medium spiny neurons had increased capacitance, decreased sEPSC frequency, and reduced intrinsic excitability. The results suggest that torsinA in the D1R-expressing cells plays an important role in the electrophysiological function and motor performance. Medical interventions to the direct pathway may affect the onset and symptoms of this disorder.
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http://dx.doi.org/10.1016/j.bbr.2021.113381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323984PMC
August 2021

Inhibitory effects of sodium new houttuyfonate on growth and biofilm formation of Streptococcus mutans.

Microb Pathog 2021 Aug 20;157:104957. Epub 2021 May 20.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, 610041, China. Electronic address:

The present study aimed to assess the impact of sodium new houttuyfonate (SNH) on growth and biofilm formation of Streptococcus mutans, and the combinatorial effects of SNH with cariostatic agents. The effects of SNH on S. mutans planktonic cultures were assessed by growth curve assay. The effects of SNH on S. mutans biofilm and extracellular polysaccharides (EPS) production were observed via crystal violet (CV) assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, colony-forming unit (CFU) counting assay, scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). Quantitative real-time polymerase chain reaction (qPCR) was applied to investigate the regulatory effects of SNH on the expression of virulence genes of S. mutans. Checkerboard microdilution assay was performed to investigate the combinatorial effects of SNH with two common cariostatic agents. SNH acted as an inhibitor on planktonic cell growth, biofilm formation and EPS production of S. mutans. SNH also downregulated the expression of gtfBCD and comDE systems and exhibited synergism with chlorhexidine (CHX). In conclusion, this study indicated a possibility for SNH to become an anticaries agents by its antimicrobial activity and synergistic effects with CHX against S. mutans.
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http://dx.doi.org/10.1016/j.micpath.2021.104957DOI Listing
August 2021

Risk of breast cancer and prediagnostic urinary excretion of bisphenol A, triclosan and parabens: The Multiethnic Cohort Study.

Int J Cancer 2021 10 3;149(7):1426-1434. Epub 2021 Jun 3.

Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA.

Exposure to bisphenol A (BPA), triclosan and parabens is widespread but their impact on breast cancer risk remains unclear. This nested case-control study investigated endocrine-disrupting chemicals (EDCs) and breast cancer risk within the Multiethnic Cohort (MEC). We measured prediagnostic urinary BPA, triclosan and parabens in 1032 postmenopausal women with breast cancer (48 African American, 77 Latino, 155 Native Hawaiian, 478 Japanese American and 274 White) and 1030 individually matched controls, using a sensitive and validated liquid chromatography mass spectrometry assay. Conditional logistic regression was used to examine risk with these EDCs with adjustment for creatinine and potential confounders. In all women, breast cancer risk was not associated with BPA (P  = 0.53) and was inversely associated with triclosan (OR  = 0.83, 95% CI: 0.66-1.04, P  = 0.045) and total parabens (OR  = 0.77, 95% CI: 0.62-0.97, P  = 0.03). While risk of hormone receptor positive (HR+) cancer was 20% to 23% lower among women in the upper two tertiles of paraben exposure (P  = 0.02), risk of HR negative (HR-) was reduced 27% but only among those in the upper tertile of exposure. Although risk associations did not differ significantly by ethnicity or by body mass index (BMI), the inverse association with triclosan was observed mainly among overweight/obese women (OR  = 0.76, 95% CI: 0.56-1.02, P  = 0.02). In summary, breast cancer risk in a multiethnic population was unrelated to BPA and was weakly inversely associated with triclosan and paraben exposures. Studies with multiple urine samples collected before breast cancer diagnosis are needed to further investigate these EDCs and breast cancer risk.
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http://dx.doi.org/10.1002/ijc.33692DOI Listing
October 2021

Hyaluronidase-responsive phototheranostic nanoagents for fluorescence imaging and photothermal/photodynamic therapy of methicillin-resistant infections.

Biomater Sci 2021 Jun;9(12):4484-4495

State Key Laboratory for Organic Electronics and Information Displays & Jiangsu Key Laboratory for Biosensors, Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Centre for Advanced Materials (SICAM), Nanjing University of Posts and Telecommunications, Nanjing 210023, China.

Infectious diseases associated with antibiotic-resistant bacteria are ever-growing threats to public health. Effective treatment and detection methods of bacterial infections are in urgent demand. Herein, novel phototheranostic nanoagents ([email protected] nanosheets, MHC NSs) with hyaluronidase (HAase)-responsive fluorescence imaging (FLI) and photothermal/photodynamic therapy (PTT/PDT) functions were prepared. In this design, Ce6 is used as both a photosensitizer and a fluorescent probe, while MoS2 nanosheets (MoS2 NSs) serve as both a fluorescence quencher and a photothermal agent. Hyaluronic acid conjugated with Ce6 (HA-Ce6) was assembled on the surface of MoS2 NSs to form MHC NSs. Without the HAase secreted by methicillin-resistant Staphylococcus aureus (MRSA), the fluorescence of Ce6 is quenched by MoS2 NSs, while in the presence of MRSA, HAase can degrade the HA and release Ce6, which restores the fluorescence and photodynamic activity of Ce6. The experimental results show that MHC NSs can fluorescently image the MRSA both in vitro and in vivo by HAase activation. Meanwhile, MHC NSs can serve as PTT/PDT dual-mode antibacterial agents for MRSA. In vitro antibacterial results show that MHC NSs can kill 99.97% MRSA under 635 nm and 785 nm laser irradiation. In vivo study further shows that MHC NSs can kill 99.9% of the bacteria in MRSA infected tissues in mice and prompt wound healing by combined PTT/PDT. This work provides novel HAase-responsive phototheranostic nanoagents for effective detection and treatment of bacterial infections.
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http://dx.doi.org/10.1039/d1bm00406aDOI Listing
June 2021

Integrating Electronic Health Record, Cancer Registry, and Geospatial Data to Study Lung Cancer in Asian American, Native Hawaiian, and Pacific Islander Ethnic Groups.

Cancer Epidemiol Biomarkers Prev 2021 Aug 17;30(8):1506-1516. Epub 2021 May 17.

Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California.

Background: A relatively high proportion of Asian American, Native Hawaiian, and Pacific Islander (AANHPI) females with lung cancer have never smoked. We used an integrative data approach to assemble a large-scale cohort to study lung cancer risk among AANHPIs by smoking status with attention to representation of specific AANHPI ethnic groups.

Methods: We leveraged electronic health records (EHRs) from two healthcare systems-Sutter Health in northern California and Kaiser Permanente Hawai'i-that have high representation of AANHPI populations. We linked EHR data on lung cancer risk factors (i.e., smoking, lung diseases, infections, reproductive factors, and body size) to data on incident lung cancer diagnoses from statewide population-based cancer registries of California and Hawai'i for the period between 2000 and 2013. Geocoded address data were linked to data on neighborhood contextual factors and regional air pollutants.

Results: The dataset comprises over 2.2 million adult females and males of any race/ethnicity. Over 250,000 are AANHPI females (19.6% of the female study population). Smoking status is available for over 95% of individuals. The dataset includes 7,274 lung cancer cases, including 613 cases among AANHPI females. Prevalence of never-smoking status varied greatly among AANHPI females with incident lung cancer, from 85.7% among Asian Indian to 14.4% among Native Hawaiian females.

Conclusion: We have developed a large, multilevel dataset particularly well-suited to conduct prospective studies of lung cancer risk among AANHPI females who never smoked.

Impact: The integrative data approach is an effective way to conduct cancer research assessing multilevel factors on cancer outcomes among small populations.
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http://dx.doi.org/10.1158/1055-9965.EPI-21-0019DOI Listing
August 2021

HSP47 contributes to angiogenesis by induction of CCL2 in bladder cancer.

Cell Signal 2021 Sep 14;85:110044. Epub 2021 May 14.

Institute of Urology, The Third Affiliated Hospital of Shenzhen University (Luohu Hospital Group), Shenzhen 518000, China; Shenzhen Following Precision Medical Research Institute, Luohu Hospital Group, Shenzhen 518000, China; Teaching Center of Shenzhen Luohu Hospital, Shantou University Medical College, Shenzhen 518000, China. Electronic address:

Heat shock protein 47 (HSP47) is a collagen-specific molecular chaperone and is involved in tumor progression by promoting angiogenesis. However, the regulatory network of HSP47 in angiogenesis remains elusive. In this study, we report a novel mechanism of HSP47-induced angiogenesis in bladder cancer (BC). We find that HSP47 is abnormally overexpressed in BC and is correlated with poor prognosis. HSP47 down-regulation suppresses angiogenesis in BC cells. Mechanistically, activation of the ERK pathway and induction of C-C Motif Chemokine Ligand 2 (CCL2) are responsible for HSP47-induced angiogenesis. The correlation between HSP47 with CCL2 and angiogenesis is further confirmed in BC clinical samples. Taken together, our findings suggest that HSP47 contributes to BC angiogenesis by induction of CCL2 and provide a potential anti-angiogenesis target for BC therapy.
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http://dx.doi.org/10.1016/j.cellsig.2021.110044DOI Listing
September 2021

Sensing ATP: Zeolitic Imidazolate Framework-67 Is Superior to Aptamers for Target Recognition.

Anal Chem 2021 06 17;93(21):7707-7713. Epub 2021 May 17.

Department of Chemistry, Waterloo Institute for Nanotechnology, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada.

In a typical biosensor, a biomolecule such as an aptamer is used for target recognition, and a nanomaterial is used for signal generation. Herein, we communicate a reverse system using a nanomaterial for target recognition and a DNA for signaling. We discovered that a classic metal-organic framework material, zeolitic imidazolate framework (ZIF)-67, has ultrahigh selectivity for recognizing adenosine triphosphate (ATP), allowing a fluorescently labeled DNA oligonucleotide to be used for signal generation. This sensor showed up to a 24-fold increase in fluorescence upon adding 1 mM ATP, while the fluorescence increase after adding adenosine or guanosine triphosphate was less than twofold. Its selectivity is much better than that of the ATP aptamer, which binds adenosine even better. Using isothermal titration calorimetry, the selective binding of ATP was independently verified. This sensor has a detection limit of 29 nM ATP and it can even detect ATP in serum. By replacing Co with Zn to form ZIF-8 or by using CoO, the selectivity for ATP was lost. Therefore, by sophisticated material design, ultrahigh selectivity for molecular recognition can be achieved.
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http://dx.doi.org/10.1021/acs.analchem.1c00976DOI Listing
June 2021

The Importance of Glycans of Viral and Host Proteins in Enveloped Virus Infection.

Front Immunol 2021 29;12:638573. Epub 2021 Apr 29.

Department of Biochemistry and Molecular Biology, Institute of Glycobiology, Dalian Medical University, Dalian, China.

Animal viruses are parasites of animal cells that have characteristics such as heredity and replication. Viruses can be divided into non-enveloped and enveloped viruses if a lipid bilayer membrane surrounds them or not. All the membrane proteins of enveloped viruses that function in attachment to target cells or membrane fusion are modified by glycosylation. Glycosylation is one of the most common post-translational modifications of proteins and plays an important role in many biological behaviors, such as protein folding and stabilization, virus attachment to target cell receptors and inhibition of antibody neutralization. Glycans of the host receptors can also regulate the attachment of the viruses and then influence the virus entry. With the development of glycosylation research technology, the research and development of novel virus vaccines and antiviral drugs based on glycan have received increasing attention. Here, we review the effects of host glycans and viral proteins on biological behaviors of viruses, and the opportunities for prevention and treatment of viral infectious diseases.
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http://dx.doi.org/10.3389/fimmu.2021.638573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116741PMC
September 2021

Targeting cholesterol biosynthesis promotes anti-tumor immunity by inhibiting long noncoding RNA SNHG29-mediated YAP activation.

Mol Ther 2021 May 14. Epub 2021 May 14.

Department of Pathology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China. Electronic address:

Anti-tumor immunity through checkpoint inhibitors, specifically anti-programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) interaction, is a promising approach for cancer therapy. However, as early clinical trials indicate that colorectal cancers (CRCs) do not respond well to immune-checkpoint therapies, new effective immunotherapy approaches to CRC warrant further study. Simvastatin is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (CoA) reductase (HMGCR), the rate-limiting enzyme of the mevalonate (MVA) pathway for the cholesterol biosynthesis. However, little is known about the functions of simvastatin in the regulation of immune checkpoints or long noncoding RNA (lncRNA)-mediated immunoregulation in cancer. Here, we found that simvastatin inhibited PD-L1 expression and promoted anti-tumor immunity via suppressing the expression of lncRNA SNHG29. Interestingly, SNHG29 interacted with YAP and inhibited phosphorylation and ubiquitination-mediated protein degradation of YAP, thereby facilitating downregulation of PD-L1 transcriptionally. Patient-derived tumor xenograft (PDX) models and the clinicopathological analysis in samples from CRC patients further supported the role of the lncRNA SNHG29-mediated PD-L1 signaling axis in tumor microenvironment reprogramming. Collectively, our study uncovers simvastatin as a potential therapeutic drug for immunotherapy in CRC, which suppresses lncRNA SNHG29-mediated YAP activation and promotes anti-tumor immunity by inhibiting PD-L1 expression.
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http://dx.doi.org/10.1016/j.ymthe.2021.05.012DOI Listing
May 2021

Hybrid evaporative cooling of Cs atoms to Bose-Einstein condensation.

Opt Express 2021 Apr;29(9):13960-13967

The Bose-Einstein condensation (BEC) of Cs atoms offers an appealing platform for studying the many-body physics of interacting Bose quantum gases, owing to the rich Feshbach resonances that can be readily achieved in the low magnetic field region. However, it is notoriously difficult to cool Cs atoms to their quantum degeneracy. Here we report a hybrid evaporative cooling of Cs atoms to BEC. Our approach relies on a combination of the magnetically tunable evaporation with the optical evaporation of atoms in a magnetically levitated optical dipole trap overlapping with a dimple trap. The magnetic field gradient is reduced for the magnetically tunable evaporation. The subsequent optical evaporation is performed by lowering the depth of the dimple trap. We study the dependence of the peak phase space density (PSD) and temperature on the number of atoms during the evaporation process, as well as how the PSD and atom number vary with the trap depth. The results are in excellent agreement with the equation model for evaporative cooling.
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http://dx.doi.org/10.1364/OE.419854DOI Listing
April 2021

A new dynamic model and transfer learning based intelligent fault diagnosis framework for rolling element bearings race faults: Solving the small sample problem.

ISA Trans 2021 Apr 5. Epub 2021 Apr 5.

Deep Space Exploration Research Center, Harbin Institute of Technology, Harbin 150001, China.

Intelligent fault diagnosis of rolling element bearings gains increasing attention in recent years due to the promising development of artificial intelligent technology. Many intelligent diagnosis methods work well requiring massive historical data of the diagnosed object. However, it is hard to get sufficient fault data in advance in real diagnosis scenario and the diagnosis model constructed on such small dataset suffers from serious overfitting and losing the ability of generalization, which is described as small sample problem in this paper. Focus on the small sample problem, this paper proposes a new intelligent fault diagnosis framework based on dynamic model and transfer learning for rolling element bearings race faults. In the proposed framework, dynamic model of bearing is utilized to generate massive and various simulation data, then the diagnosis knowledge learned from simulation data is leveraged to real scenario based on convolutional neural network (CNN) and parameter transfer strategies. The effectiveness of the proposed method is verified and discussed based on three fault diagnosis cases in detail. The results show that based on the simulation data and parameter transfer strategies in CNN, the proposed method can learn more transferable features and reduce the feature distribution discrepancy, contributing to enhancing the fault identification performance significantly.
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http://dx.doi.org/10.1016/j.isatra.2021.03.042DOI Listing
April 2021

Nitazoxanide impairs mitophagy flux through ROS-mediated mitophagy initiation and lysosomal dysfunction in bladder cancer.

Biochem Pharmacol 2021 Aug 4;190:114588. Epub 2021 May 4.

Institute of Urology, The Third Affiliated Hospital of Shenzhen University (Luohu Hospital Group), Shenzhen 518000, China; Shenzhen Following Precision Medical Research Institute, Luohu Hospital Group, Shenzhen 518000, China; Teaching Center of Shenzhen Luohu Hospital, Shantou University Medical College, Shenzhen 518000, China; Department of Urology and Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510000, China. Electronic address:

Bladder cancer is one of the most common malignancy in the urinary tract with high recurrence and drug resistance in clinics. Alternative treatments from existing drugs might be a promising strategy. Nitazoxanide (NTZ), an FDA-approved antiprotozoal drug, has got increasingly noticed because of its favorable safety profile and antitumor potential, yet the effects in bladder cancer and underlying mechanisms remain poorly understood. Herein, we find that NTZ induces mitochondrial damage and mitophagy initiation through PINK1-generated phospho-ubiquitin(pS65-Ub) and autophagy receptor-mediated pathway even in the absence of Atg5/Beclin1. Meanwhile, NTZ inhibits lysosomal degradation activity, leading to mitophagy flux impairment at late stage. Mitochondrial reactive oxygen species (ROS) production is critical in this process, as eliminating ROS with N-acetylcysteine (NAC) efficiently inhibits PINK1 signaling-mediated mitophagy initiation and alleviates lysosomal dysfunction. Co-treatment with NTZ and autophagy inhibitor Chloroquine (CQ) to aggravate mitophagy flux impairment promotes NTZ-induced apoptosis, while alleviation of mitophagy flux impairment with ROS scavenger reduces cell death. Moreover, we also discover a similar signaling response in the 3D bladder tumor spheroid after NTZ exposure. In vivo study reveals a significant inhibition of orthotopic bladder tumors with no obvious systemic toxicity. Together, our results uncover the anti-tumor activities of NTZ with the involvement of ROS-mediated mitophagy modulation at different stages and demonstrate it as a potential drug candidate for fighting against bladder tumors.
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http://dx.doi.org/10.1016/j.bcp.2021.114588DOI Listing
August 2021
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