Publications by authors named "Qing Chang"

788 Publications

Room-temperature preparation of highly efficient NH-MIL-101(Fe) catalyst: The important role of -NH in accelerating Fe(III)/Fe(II) cycling.

Chemosphere 2021 Nov 22:133026. Epub 2021 Nov 22.

Key Laboratory of Catalysis and Materials Science of Hubei Province, College of Resources and Environmental Science, South-Central University for Nationalities, Wuhan, 430074, Hubei, China.

The slow redox rate of Fe(III)/Fe(II) couples is a rate-limiting step for Fenton-like performance of Fe-MOFs. In this study, a series of catalysts (MIL-101) with various p-phthalic acid/2-aminoterephthalic acid (HBDC/NH-HBDC) molar ratios were prepared using a simple and mild chemical method and applied for catalyzed degradation of bisphenol A (BPA). Interestingly, the -NH modified MIL-101(Fe) can adjust Fe-Oxo node by increasing the electron density of Fe(III) in the presence of -NH group with high electron density, thus forming Fe(II) in situ in MOFs. Meanwhile, the -NH groups used as electron-donors can promote electron transfer, resulting in faster Fe(III)→Fe(II) half-reaction and active HO to continuously generate •OH radical. The BPA degradation and rate constant of Fe-BDC-NH/HO system are 15.4-fold and 86.8-fold higher than that of Fe-BDC/HO system, respectively. The density functional theory (DFT) calculations showed that Fe-BDC-NH possesses higher Fermi level energy (-4.88 eV) and lower activation energy barriers (0.32 eV) compared with Fe-BDC. Moreover, Fe-BDC-NH showed good reusability and stability. This work offers a highly efficient and stable MOFs-based Fenton-like catalyst to rapidly degrade organic pollutants over a wide pH range for potential applications in wastewater treatment.
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http://dx.doi.org/10.1016/j.chemosphere.2021.133026DOI Listing
November 2021

Pressure-Controlled Encapsulation of Graphene Quantum Dots into Liposomes by the Reverse-Phase Evaporation Method.

Langmuir 2021 Nov 22. Epub 2021 Nov 22.

Institute of Nanochemistry and Nanobiology, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, China.

Ultrasmall nanoparticles (USNPs) with sizes below 10 nm have shown great potentials in medical applications owing to their outstanding physical, chemical, optical, and biological properties. However, they suffer from a rapid renal clearance and biodegradation rate in the biological environment due to the small size. Liposomes are one of the most promising delivery nanocarriers for loading USNPs because of their excellent biocompatibility and lipid bilayer structure. Encapsulation of USNPs into liposomes in an efficient and controllable manner remains a challenge. In this study, we achieved a high loading of graphene quantum dots (GQDs, ∼4 nm), a typical USNP, into the aqueous core of liposomes (45.68 ± 1.44%), which was controllable by the pressure. The GQDs-loaded liposomes (GQDs-LPs) exhibited a very good aqueous stability for over a month. Furthermore, indocyanine green (ICG), an efficient near-infrared (NIR) photothermal agent, was introduced in the GQDs-LP system that could convert NIR laser energy into thermal energy and break down the liposomes, causing the release of GQDs in 6 min. Moreover, this NIR light-controlled release system (GQDs-ICG-LPs) also exhibited a good photothermal therapeutic performance , and 75% of cancer cells were killed at a concentration of 200 μg/mL. Overall, the successful development of the NIR light-controlled release system has laid a solid foundation for the future biomedical application of USNPs-loaded liposomes.
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http://dx.doi.org/10.1021/acs.langmuir.1c02338DOI Listing
November 2021

PKM2 Is a Potential Diagnostic and Therapeutic Target for Retinitis Pigmentosa.

Dis Markers 2021 11;2021:1602797. Epub 2021 Nov 11.

Department of Ophthalmology and Vision Science, Eye and Ear, Nose and Throat Hospital of Fudan University, Shanghai 200031, China.

Retinitis pigmentosa (RP) is a major cause of blindness that is difficult to diagnose and treat. PKM2, a subtype of pyruvate kinase, is strongly associated with oxidative stress and is expressed in photoreceptors. We investigated whether PKM2 reduces photoreceptor cell apoptosis and evaluated possible antiapoptotic mechanisms in RP. We established RP models by exposing 661W cells to blue light and modulated PKM2 activity using a PKM2 inhibitor. We measured the apoptosis rates using calcein-acetoxymethyl ester/propidium iodide double staining and Cell Counting Kit-8, the oxidative stress levels using a reactive oxygen species assay, and the changes in protein expression by western blotting. Photodamage increased PKM2 expression, cellular oxidative stress, and apoptosis of 661W cells. PKM2 inhibition significantly reduced the levels of apoptosis and oxidative stress induced by photodamage. Our data suggest that PKM2 is a potential disease marker and therapeutic target for RP.
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http://dx.doi.org/10.1155/2021/1602797DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8601838PMC
November 2021

Flagellin maintains eosinophils in the intestine.

Cytokine 2021 Nov 16;150:155769. Epub 2021 Nov 16.

Department of Otolaryngology, Longgang Central Hospital, Shenzhen, China. Electronic address:

Eosinophils (Eos) are the major effector cells in allergic response. The regulation of Eo is not fully understood yet. Flagellin (FGN) has immune regulatory functions. This study aims to elucidate the role of FGN in maintaining Eo at the static status in the intestinal tissues. A mouse food allergy (FA) model was developed. Eo mediator levels in the serum or culture supernatant or intestinal lavage fluids were assessed and used as an indicator of Eo activation. The results showed that less FGN amounts were detected in the FA mouse intestinal tissues, that were negatively correlated with the Eo activation. Mast cell-derived chymase bound FGN to induce FGN degradation. FGN formed complexes with FcγRI on Eos to prevent specific antigens from binding FcγRI, and thus, to prevent Eo activation. Administration of FGN efficiently alleviated experimental FA. In conclusion, FGN plays a critical role in maintaining Eos at static status in the intestine. Administration of FGN can alleviate experimental FA. FGN may be a novel drug candidate to be used in the treatment of Eo-related diseases.
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http://dx.doi.org/10.1016/j.cyto.2021.155769DOI Listing
November 2021

A bifunctional nanozyme of carbon dots-mediated CoS formation.

J Colloid Interface Sci 2021 Oct 21;608(Pt 2):1348-1354. Epub 2021 Oct 21.

Research Group of New Energy Materials and Devices, North University of China, Taiyuan 030051, PR China. Electronic address:

Controlling the size of nanocrystals and inhibiting their agglomeration are of paramount importance for achieving ideal catalytic performance. Here we discovered that carbon dots (CDs) are not only able to serve as reductants but also as stabilizers of ultrasmall CoS nanocrystals by means of their surface terminal groups. As a result, ultrasmall CoS nanocrystals are incorporated into porous carbon nanosheets formed by splicing CDs. The resultant nanocomposites display a rich pore structure accompanying with large specific surface area and outstanding bifunctional performances to mimic the catalytic activity of peroxidase and oxidase without exerting any external energy. More importantly, the unique architecture endows CoS nanocrystals with high stability and good durability. The nanocomposites have been demonstrated as a colorimetric sensor for detection of ascorbic acid with a superior anti-interference ability as well as a detection limit of 0.2 μM. Our findings open new synthetic opportunities by tuning the interaction of CDs with the surrounding environment and enable advanced applications such as biomedicine and catalytic transformations.
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http://dx.doi.org/10.1016/j.jcis.2021.10.103DOI Listing
October 2021

Enhanced Photothermal Performance by Carbon Dot-Chelated Polydopamine Nanoparticles.

ACS Biomater Sci Eng 2021 Nov 5. Epub 2021 Nov 5.

Institute of Nanochemistry and Nanobiology, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, China.

Polydopamine (PDA) has been widely used in biomedical applications including imaging contrast agents, antioxidants, UV protection, and photothermal therapy due to its biocompatibility, metal-ion chelation, free-radical scavenging, and wideband absorption, but its low photothermal efficiency still needs to be improved. In this study, we chelated near-infrared (NIR) sensitive carbon quantum dots on the surface of polydopamine ([email protected],S-CQDs) to increase its near-infrared absorption. Surprisingly, although only 4% (w/w) of carbon quantum dots was conjugated on the PDA surface, it still increased the photothermal efficiency by 30%. Moreover, [email protected],S-CQDs could also be used as the drug carrier for loading 60% (w/w) of the DOX and achieved stimuli-responsive drug release under lysosomal pH (pH 5.0) and 808 nm laser illumination. For therapeutic experiment, [email protected],S-CQDs showed the remarkable therapeutic performance under 808 nm laser irradiation for killing 90% of cancer cells compared with 50% by pure PDA nanoparticles, and the efficacy was even higher after loading DOX owing to the synergistic effect by photothermal therapy and chemotherapy. This intelligent and effective therapeutic nanosystem based on [email protected],S-CQDs showed enhanced photothermal behavior after chelating carbon dots and promoted the future development of a nanoplatform for stimuli-responsive photothermal/chemo therapy.
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http://dx.doi.org/10.1021/acsbiomaterials.1c01045DOI Listing
November 2021

Molybdenum Selenide/Porous Carbon Nanomaterial Heterostructures with Remarkably Enhanced Light-Boosting Peroxidase-like Activities.

ACS Appl Mater Interfaces 2021 Nov 3;13(45):54274-54283. Epub 2021 Nov 3.

School of Energy and Power Engineering & School of Material Science and Engineering, North University of China, Taiyuan 030051, P. R. China.

Nanozymes have emerged as a fascinating nanomaterial with enzyme-like characteristics for addressing the limitations of natural enzymes. Nevertheless, how to improve the relatively low catalytic activity still remains challenging. Herein, a facile recrystallizing salt template-assisted chemical vapor deposition method was utilized to synthesize MoSe/PCN heterostructures. This heterostructure displays remarkably enhanced light boosting peroxidase-like activities. Notably, the maximal reaction velocity of this heterostructure attains 17.81 and 86.89 μM min [for -phenylenediamine (OPD) and 3,3'5,5'-tetramethylbenzidine (TMB), respectively]. Moreover, various characterization means were performed to explore the mechanism deeply. It is worth mentioning that the photoinduced electrons generated by the heterostructure directly react with HO to yield plentiful OH for the effective oxidation of OPD and TMB. Therefore, this work offers a promising approach for improving peroxidase-like activity by light stimulation and actuating the development of enzyme-based applications.
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http://dx.doi.org/10.1021/acsami.1c16569DOI Listing
November 2021

Elevation of brain magnesium with Swiss chard and buckwheat extracts in an animal model of reduced magnesium dietary intake.

Nutr Neurosci 2021 Nov 3:1-12. Epub 2021 Nov 3.

PsychoGenics Inc., Paramus, NJ, USA.

Objectives: Inadequate dietary magnesium (Mg) intake is a growing public health concern. Mg is critical for diverse metabolic processes including energy production, macromolecule biosynthesis, and electrolyte homeostasis. Inadequate free Mg ion concentration ([Mg]) in the brain is associated with several neurological and behavioral disorders. Elevating [Mg]in the brain using oral Mg supplementation has proven to be challenging due to the tight regulation of Mg transport to the brain. This study explored the effect of short-term moderate reduction in dietary Mg intake (87% of normal Mg diet for 30 days) on [Mg] in the cerebrospinal fluid (CSF) ([Mg]) and red blood cells (RBCs) ([Mg]) in adult male rats. In addition, we investigated the effectiveness of magnesium-rich blend of Swiss chard and buckwheat extracts (SC/BW extract) in increasing brain [Mg] compared to various Mg salts commonly used as dietary supplements.

Methods: Animals were assigned to either normal or low Mg diet for 30 - 45 days. Following this, animals maintained on low Mg diet were supplemented with various Mg compounds. [Mg] and [Mg] were measured at baseline and following Mg administration. Anxiety-like behavior and cognitive function were also evaluated.

Results: The present study showed that a short-term and moderate reduction in Mg dietary intake results in a significant decline in [Mg] and [Mg] and the emergence of anxiety-like behavior in comparison to animals maintained on normal Mg diet. Supplementation with SC/BW extract significantly elevated [Mg] and improved animal performance in the novel object recognition test in comparison with animals maintained on reduced Mg intake and supplemented with various Mg compounds.

Discussion: These observations indicate that brain [Mg] is more sensitive to a short-term and moderate reduction in Mg dietary intake than previously thought and emphasizes the importance of dietary Mg in replenishing brain Mg reserves.
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http://dx.doi.org/10.1080/1028415X.2021.1995119DOI Listing
November 2021

The correlation between fibroblast growth factor-23 and ESRD patients with hearing impairment.

PeerJ 2021 13;9:e12295. Epub 2021 Oct 13.

Department of Nephrology, The First Affiliated Hospital of Kunming Medical University, Kunming, China.

Background: End-stage renal disease (ESRD) patients often experience hearing impairment, resulting in a high rate of disability and a decline in their quality of life. Fibroblast growth factor-23 (FGF23) is a diagnostic biomarker for chronic kidney disease (CKD) and a pathogenic contributor to CKD progression. However, the correlation between FGF23 level and CKD patients with hearing impairment remains elusive. This study aimed to investigate the relationship between the FGF23 and ESRD accompanied with hearing impairment.

Methods: A total of 144 ESRD patients, who were admitted to the First Affiliated Hospital of Kunming Medical University from November to December 2020, were enrolled in this study. Firstly, 144 ESRD patients underwent pure-tone audiometry (PTA). Secondly, it was attempted to randomly select 20 ESRD patients with normal hearing, and 20 ESRD patients with hearing impairment (match ratio, 1:1). Age- and gender-matched healthy people ( = 20) were also recruited as controls group. The expression levels of FGF23 was detected by enzyme-linked immunosorbent assay (ELISA).

Results: The results of pure-tone audiometry showed that the prevalence of hearing impairment in ESRD patients was 80.5%. Male ESRD patients were more likely to develop hearing impairment compared to female patients. The incidence rate of hearing impairment at a high frequency was significantly higher than that at a low frequency ( < 0.01). The serum levels of FGF23, phosphorus, and parathyroid hormone (PTH) in ESRD patients with hearing impairment significantly increased compared with those with normal hearing and healthy controls.

Conclusion: ESRD patients had a higher risk of hearing loss, especially high-frequency hearing impairment. As FGF23 level increased, the risk of hearing loss was also elevated. The hearing impairment in ESRD patients was associated with the degree of kidney injury, and serum FGF23 level.
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http://dx.doi.org/10.7717/peerj.12295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8520394PMC
October 2021

MiR-222-3p promotes the proliferation, migration and invasion of papillary thyroid carcinoma cells through targeting SLC4A4.

Histol Histopathol 2021 Oct 28:18387. Epub 2021 Oct 28.

Department of Head and Neck, Tangshan Gongren Hospital, Tangshan, China.

Objective: An increasing number of studies indicate that miR-222-3p is upregulated in various cancers and can regulate tumor progression. This study aimed to explore the regulatory mechanism of miR-222-3p in papillary thyroid carcinoma (PTC).

Methods: TCGA database was used to dig differentially expressed miRNAs and mRNAs in PTC tissue. Relevant references were searched to determine target miRNA. StarBase, TargetScan and miRDB were applied to predict mRNAs that had binding sites with the target miRNA. Then, the mRNAs were intersected with differentially downregulated mRNAs in TCGA to determine the target mRNA. qRT-PCR was exerted to evaluate gene expression of miR-222-3p and SLC4A4 in PTC. Western blot was performed out to evaluate the protein expression of SLC4A4 in PTC cells. CCK-8, wound healing assay and cell invasion assay were undertaken to observe the proliferative, migratory, and invasive abilities of PTC cells. Dual-luciferase assay was employed to test the binding relationship between miR-222-3p and SLC4A4.

Results: MiR-222-3p was highly expressed in PTC while SLC4A4 was lowly expressed. Moreover, miR-222-3p was able to promote the proliferation, invasion, and migration of PTC cells. SLC4A4 was able to reverse these promotive effects of miR-222-3p.

Conclusion: MiR-222-3p can promote the proliferation, migration and invasion of PTC cells through targeting SLC4A4. MiR-222-3p is expected to be a molecular therapeutic target for PTC patients.
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http://dx.doi.org/10.14670/HH-18-387DOI Listing
October 2021

Associations between long term exposures to outdoor air pollution and indoor solid fuel use and depression in China.

J Environ Manage 2022 Jan 23;302(Pt A):113982. Epub 2021 Oct 23.

Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Heping District, Sanhao Street, No. 36, Shenyang, Liaoning Province, 110004, China. Electronic address:

Depression is one of the most common mental disorders. Effects of air pollution from outdoor and indoor on depression were inconsistent. We assessed 30,139 participants from Northeast China to explore the associations between long term exposures of outdoor and indoor solid fuel use and depressive symptoms. Multiple logistic regressions models as well as multiplicative interaction and additive interaction analysis were used. Outdoor exposures to air pollutants of particulate matter (with an aerodynamic diameter <2.5 μm, [PM], odds ratio [OR] = 1.98 per standard deviation [SD], 95% confidence interval [CI]: 1.78, 2.19; with an aerodynamic diameter <10 μm, [PM], OR = 1.83, 95% CI:1.68, 2.00), sulfur dioxide (SO, OR = 1.42, 95% CI: 1.33, 1.52), and nitrogen dioxide (NO, OR = 1.62, 95% CI: 1.49, 1.76) were significantly associated with higher occurrence of depressive symptoms. A significant linear trend for increased occurrence of depressive symptoms was observed in participants using both solid fuels for cooking and heating (P = 0.04). Indoor air pollution exposures from solid fuel use for heating (OR = 1.16, 95%CI: 1.00, 1.35) and high cooking frequency (OR = 1.17, 95%CI: 1.00, 1.37) were significantly associated with increased occurrence of depressive symptoms. We observed significant interactions of indoor solid fuel use and outdoor air pollution exposures on depressive symptoms (indoor fuel use for cooking and SO, P value = 0.04; solid fuel use for heating and NO, P value = 0.02). Solid fuel use for cooking weakened the associations between SO(relative excess risk due to interaction [RERI] = -1.37, 95% CI: -1.88, -0.86) and depressive symptoms. Solid fuel use for heating weakened the associations between NO (RERI = -1.91, 95% CI: -2.55, -1.27) and depressive symptoms. Compared with individual associations, antagonistic interactions of outdoor air pollution and indoor solid fuel use on depressive symptoms might exist. Our findings contribute to better understandings for the associations between air pollution and depressive symptoms, which might be useful for developing effective strategies for depression prevention and air pollution control.
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http://dx.doi.org/10.1016/j.jenvman.2021.113982DOI Listing
January 2022

Construction and Evaluation of a Tumor Mutation Burden-Related Prognostic Signature for Thyroid Carcinoma.

Comput Math Methods Med 2021 14;2021:1435827. Epub 2021 Oct 14.

Department of Head and Neck Surgery, Tangshan Gongren Hospital, Tangshan, Hebei 063003, China.

Thyroid carcinoma is a type of prevalent cancer. Its prognostic evaluation depends on clinicopathological features. However, such conventional methods are deficient. Based on mRNA, single nucleotide variants (SNV), and clinical information of thyroid carcinoma from The Cancer Genome Atlas (TCGA) database, this study statistically analyzed mutational signature of patients with this disease. Missense mutation and SNV are the most common variant classification and variant type, respectively. Next, tumor mutation burden (TMB) of sample was calculated. Survival status of high/low TMB groups was analyzed, as well as the relationship between TMB and clinicopathological features. Results revealed that patients with high TMB had poor survival status, and TMB was related to several clinicopathological features. Through analysis on DEGs in high/low TMB groups, 381 DEGs were obtained. They were found to be mainly enriched in muscle tissue development through enrichment analysis. Then, through Cox regression analysis, a 5-gene prognostic signature was established, which was then evaluated through survival curves and receiver operation characteristic (ROC) curves. The result showed that the signature was able to effectively predict patient's prognosis and to serve as an independent prognostic risk factor. Finally, through Gene Set Enrichment Analysis (GSEA) on high/low-risk groups, DEGs were found to be mainly enriched in signaling pathways related to DNA repair. Overall, based on the TCGA-THCA dataset, we constructed a 5-gene prognostic signature through a trail of bioinformatics analysis.
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http://dx.doi.org/10.1155/2021/1435827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8538398PMC
October 2021

Genotypic spectrum and phenotype correlations of EYS-associated disease in a Chinese cohort.

Eye (Lond) 2021 Oct 23. Epub 2021 Oct 23.

Eye Institute, Eye and ENT Hospital, College of Medicine, Fudan University, Shanghai, China.

Background: To date, certain efforts have been made to investigate the clinical and genetic characteristics of patients with EYS mutations. However, data for Chinese patients are limited.

Objectives: To perform a detailed phenotyping and genetic characterization of 55 Chinese patients with EYS-RD, and to identify risk factors for these clinical data.

Methods: A total of 55 patients with EYS-RD were recruited. Best-corrected visual acuity (BCVA), patient age, age at symptom onset, disease duration, and genetic information were collected.

Results: Thirty-six novel variants, three hot mutations of EYS (30.3%, c.6416G>A, c.6557G>A, c.7492G>C) and one hot region (49.06%, Laminin G domains) were identified. In all, 36.84% of the mutations occurred at base G site, and majority of mutations (56.56%) were missense. Late-truncating mutations are significantly more prevalent (41.30%). The mean age of onset was 15.65 ± 14.67 years old; it had no significant correlation with genotype. The average BCVA was 0.73 ± 0.93 LogMAR, and 61.8% of eyes had a BCVA better than 0.52 logMAR. BCVA was positively correlated with disease duration time. The mean MD was 23.18 ± 7.34 dB, MD showed a significant correlation with genotype and age. Cataract was present in 56.45% of patients, and 42.59% of patients showed an absence of pigmentation in the retina. Cataract and hyperpigmentation both showed a significant correlation with age.

Conclusions: EYS-RD is associated with a moderate phenotype with onset around adolescence, but great variability. Our study largely enhances the current knowledge of phenotypic and genotypic characteristics of EYS-RD, which could pave the way for better management of these patients.
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http://dx.doi.org/10.1038/s41433-021-01794-6DOI Listing
October 2021

Loss of FBXO31-mediated degradation of DUSP6 dysregulates ERK and PI3K-AKT signaling and promotes prostate tumorigenesis.

Cell Rep 2021 Oct;37(3):109870

Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, The Alexandria Center for Life Science, New York, NY 10016, USA; Laura and Isaac Perlmutter Cancer Center, NYU Grossman School of Medicine, The Alexandria Center for Life Science, New York, NY 10016, USA; Howard Hughes Medical Institute, NYU Grossman School of Medicine, The Alexandria Center for Life Science, New York, NY 10016, USA. Electronic address:

FBXO31 is the substrate receptor of one of many CUL1-RING ubiquitin ligase (CRL1) complexes. Here, we show that low FBXO31 mRNA levels are associated with high pre-operative prostate-specific antigen (PSA) levels and Gleason grade in human prostate cancer. Mechanistically, the ubiquitin ligase CRL1 promotes the ubiquitylation-mediated degradation of DUSP6, a dual specificity phosphatase that dephosphorylates and inactivates the extracellular-signal-regulated kinase-1 and -2 (ERK1/2). Depletion of FBXO31 stabilizes DUSP6, suppresses ERK signaling, and activates the PI3K-AKT signaling cascade. Moreover, deletion of FBXO31 promotes tumor development in a mouse orthotopic model of prostate cancer. Treatment with BCI, a small molecule inhibitor of DUSP6, suppresses AKT activation and prevents tumor formation, suggesting that the FBXO31 tumor suppressor activity is dependent on DUSP6. Taken together, our studies highlight the relevance of the FBXO31-DUSP6 axis in the regulation of ERK- and PI3K-AKT-mediated signaling pathways, as well as its therapeutic potential in prostate cancer.
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http://dx.doi.org/10.1016/j.celrep.2021.109870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8577224PMC
October 2021

Host EPAC1 Modulates Rickettsial Adhesion to Vascular Endothelial Cells via Regulation of ANXA2 Y23 Phosphorylation.

Pathogens 2021 Oct 12;10(10). Epub 2021 Oct 12.

Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA.

Introduction: Intracellular cAMP receptor exchange proteins directly activated by cAMP 1 () regulate obligate intracellular parasitic bacterium rickettsial adherence to and invasion into vascular endothelial cells (ECs). However, underlying precise mechanism(s) remain unclear. The aim of the study is to dissect the functional role of the signaling pathway during initial adhesion of rickettsiae to EC surfaces.

Methods: In the present study, an established system that is anatomically based and quantifies bacterial adhesion to ECs in vivo was combined with novel fluidic force microscopy (FluidFM) to dissect the functional role of the signaling pathway in rickettsiae-EC adhesion.

Results: The deletion of the gene impedes rickettsial binding to endothelium in vivo. Rickettsial OmpB shows a host -dependent binding strength on the surface of a living brain microvascular EC (BMEC). Furthermore, ectopic expression of phosphodefective and phosphomimic mutants replacing tyrosine (Y) 23 of in -knock out BMECs results in different binding force to reOmpB in response to the activation of .

Conclusions: modulates rickettsial adhesion, in association with Y23 phosphorylation of the binding receptor . Underlying mechanism(s) should be further explored to delineate the accurate role of cAMP- system during rickettsial infection.
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http://dx.doi.org/10.3390/pathogens10101307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8537355PMC
October 2021

Intracellular receptor EPAC regulates von Willebrand factor secretion from endothelial cells in a PI3K-/eNOS-dependent manner during inflammation.

J Biol Chem 2021 11 20;297(5):101315. Epub 2021 Oct 20.

Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA. Electronic address:

Coagulopathy is associated with both inflammation and infection, including infections with novel severe acute respiratory syndrome coronavirus-2, the causative agent Coagulopathy is associated with both inflammation and infection, including infection with novel severe acute respiratory syndrome coronavirus-2, the causative agent of COVID-19. Clot formation is promoted via cAMP-mediated secretion of von Willebrand factor (vWF), which fine-tunes the process of hemostasis. The exchange protein directly activated by cAMP (EPAC) is a ubiquitously expressed intracellular cAMP receptor that plays a regulatory role in suppressing inflammation. To assess whether EPAC could regulate vWF release during inflammation, we utilized our EPAC1-null mouse model and revealed increased secretion of vWF in endotoxemic mice in the absence of the EPAC1 gene. Pharmacological inhibition of EPAC1 in vitro mimicked the EPAC1-/- phenotype. In addition, EPAC1 regulated tumor necrosis factor-α-triggered vWF secretion from human umbilical vein endothelial cells in a manner dependent upon inflammatory effector molecules PI3K and endothelial nitric oxide synthase. Furthermore, EPAC1 activation reduced inflammation-triggered vWF release, both in vivo and in vitro. Our data delineate a novel regulatory role for EPAC1 in vWF secretion and shed light on the potential development of new strategies to control thrombosis during inflammation.
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http://dx.doi.org/10.1016/j.jbc.2021.101315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8526113PMC
November 2021

Single-cell analyses reveal key immune cell subsets associated with response to PD-L1 blockade in triple-negative breast cancer.

Cancer Cell 2021 Oct 5. Epub 2021 Oct 5.

State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. Electronic address:

In triple-negative breast cancer (TNBC), the benefit of combining chemotherapy with checkpoint inhibitors is still not very clear. We utilize single-cell RNA- and ATAC-sequencing to examine the immune cell dynamics in 22 patients with advanced TNBC treated with paclitaxel or its combination with the anti-PD-L1 atezolizumab. We demonstrate that high levels of baseline CXCL13 T cells are linked to the proinflammatory features of macrophages and can predict effective responses to the combination therapy. In responsive patients, lymphoid tissue inducer (LTi) cells, follicular B (Bfoc) cells, CXCL13 T cells, and conventional type 1 dendritic cells (cDC1) concertedly increase following the combination therapy, but instead decrease after paclitaxel monotherapy. Our data highlight the importance of CXCL13 T cells in effective responses to anti-PD-L1 therapies and suggest that their reduction by paclitaxel regimen may compromise the clinical outcomes of accompanying atezolizumab for TNBC treatment.
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http://dx.doi.org/10.1016/j.ccell.2021.09.010DOI Listing
October 2021

Associations of Nutritional, Lifestyle, and Metabolic Factors With Non-alcoholic Fatty Liver Disease: An Umbrella Review With More Than 380,000 Participants.

Front Nutr 2021 17;8:642509. Epub 2021 Sep 17.

Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China.

Nonalcoholic fatty liver disease (NAFLD) is the most common liver injury. We performed this umbrella review of meta-analyses to summarize the evidence on the associations of nutritional, lifestyle, and metabolic factors with NAFLD. We searched the PubMed, Embase, and Web of Science databases from inception until July 2, 2020, to identify meta-analyses of observational studies which explored the associations of nutritional, lifestyle, and metabolic factors with NAFLD. Evidence levels were assessed using summary effect sizes, 95% prediction intervals, between-study heterogeneity, evidence of small-study effects, and evidence of excess significance bias for each meta-analysis. (No. of PROSPERO, CRD42020200124). Twenty two risk or protective factors from 10 published meta-analyses were included and studied. Three risk factors (sugar-sweetened beverage consumption, serum fetuin-A, and waist circumference) with highly suggestive levels of evidence and three risk factors (soft drink consumption, former smoking, and body mass index) with suggestive levels of evidence were identified. Only two protective factors (physical activity and serum vitamin D level [among adults in Western countries]) with suggestive levels of evidence were identified. Furthermore, other six risk factors and two protective factors with weak levels of evidence were identified. We found varying levels of evidence of associations of nutritional, lifestyle, and metabolic factors and NAFLD. The results suggest that nutritional and lifestyle management should be considered as a major primary preventive strategy for NAFLD. Moreover, considering the low quality of included meta-analyses and limited area of research topics, future high-quality original studies and meta-analyses should be performed to study these associations.
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http://dx.doi.org/10.3389/fnut.2021.642509DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8484322PMC
September 2021

Fate of CdSe/ZnS quantum dots in cells: Endocytosis, translocation and exocytosis.

Colloids Surf B Biointerfaces 2021 Dec 25;208:112140. Epub 2021 Sep 25.

Institute of Nanochemistry and Nanobiology, Shanghai University, Shanghai 200444, China. Electronic address:

Semiconductor quantum dots (QDs) have been extensively explored for extensive bioapplications, yet their cellular fate, especially exocytosis, has not been thoroughly investigated. Herein, we systematically investigated the whole cellular process from the endocytosis, intercellular trafficking, to the exocytosis of a typical QD, core/shell CdSe/ZnS QD. Using confocal laser scanning microscopy and flow cytometry, and after carefully eliminating the effect of cell division, we found that the QDs were internalized by HeLa cells with a time-, dose-, and serum-dependent manner. The cellular uptake was inhibited by serum, but eventually peaked after 4-6 h incubation with or without serum. The primary endocytosis pathway was clathrin-mediated, and actin- and microtubule-dependent in the medium with serum, while the caveolae-mediated endocytosis and macropinocytosis were more important for the QDs in the serum-free medium. Inside cells, most QDs distributed in lysosomes, and some entered mitochondria, endoplasmic reticulum, and Golgi apparatus. The translocation of the QDs from other organelles to Golgi apparatus was observed. The exocytosis of QDs was faster than the endocytosis, reaching the maximum in about one hour after cultured in fresh culture medium, with around 60% of the internalized QDs remained undischarged. The exocytosis process was energy- and actin-dependent, and the lysosome exocytosis and endoplasmic reticulum/Golgi pathway were the main routes. This study provides a full picture of behavior and fate of QDs in cells, which may facilitate the design of ideal QDs applied in biomedical and other fields.
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http://dx.doi.org/10.1016/j.colsurfb.2021.112140DOI Listing
December 2021

Identifying 13 Hub Genes Associated with Progression and Prognosis of Hepatocellular Carcinoma with Weighted Gene Co-Expression Network Analysis.

Crit Rev Eukaryot Gene Expr 2021 ;31(4):59-69

Department of Hepatobiliary Surgery, Tangshan GongRen Hospital, Tangshan, 063000, China.

Hepatocellular carcinoma (HCC) is a type of common cancer, often accompanied by tumor recurrence and metastasis after surgery with poor prognosis. Therefore, searching into potential biomarkers that can effectively predict the prognosis and progression of HCC is crucial. In this study, we identified 1,981 differentially expressed genes (DEGs) using mRNA expression profiles from the TCGA-LIHC dataset. Subsequently, weighted gene co-expression network analysis found that the turquoise module closely associated with the pathological grade and clinical stage of HCC was identified. Then, from the key genes in the turquoise module and protein-protein interaction network analysis, 13 hub genes significantly related to the prognosis of HCC were screened. Through co-expression and functional enrichment analyses, these 13 hub genes were found to play an important role in mitosis. Finally, we evaluated the relationship between these hub genes and overall survival and disease-free survival through survival analysis. The result indicated that HCC patients with high hub gene expression had a poorer prognosis than HCC patients with low expression. Receiver operating characteristic curves showed that each hub gene could predict the prognosis of HCC patients. In summary, a total of 13 hub genes were identified that play an important role in the progression of HCC, which can be used as potential biomarkers for HCC patients.
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http://dx.doi.org/10.1615/CritRevEukaryotGeneExpr.2021038191DOI Listing
January 2021

Optimization of the Preparation Parameters of High-Strength Nickel Layers by Electrodeposition on Mild Steel Substrates.

Materials (Basel) 2021 Sep 21;14(18). Epub 2021 Sep 21.

Department of Mechanics, Tianjin University of Commerce, Tianjin 300134, China.

The electrodeposition process parameters were optimized for the acquisition of high-strength monolithic nickel layers on Q235A substrates based on the Watts nickel plating solution using the DC electrodeposition method. Based on the study of the electrochemical polarization behavior of nickel ions in Watts' plating solution, 16 experimental protocols were selected according to the orthogonal test method. The residual stress, microhardness, modulus of elasticity, and surface roughness of the nickel plating were tested by X-ray diffractometer, nano-mechanical test system, and surface profilometer, respectively, to investigate the influence of current density, temperature, and PH on the mechanical properties of nickel plating, so as to determine the best process solution for the preparation of high-strength nickel plating. The results of the study show that the mechanical properties of the nickel deposits electrodeposited onto Q235A are optimized when plating at a current density of 3 A/dm, a bath temperature of 45 °C, and a pH of 3.5. The nickel-plated layer has a minimum grain size of 34.8 nm, a microhardness of 3.86 GPa, a modulus of elasticity of 238 GPa, and a surface roughness Ra of 0.182 μm.
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http://dx.doi.org/10.3390/ma14185461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8467751PMC
September 2021

Functional Characterization of the Wheat Macrophage Migration Inhibitory Factor TaMIF1 in Wheat-Stripe Rust () Interaction.

Biology (Basel) 2021 Sep 7;10(9). Epub 2021 Sep 7.

State Key Laboratory of Crop Stress Biology for Arid Areas, College of Plant Protection, Northwest A&F University, Yangling, Xianyang 712100, China.

Macrophage migration inhibitory factor (MIF), named for its role in inhibiting macrophage/monocyte migration, has multiple functions in modulation of inflammation, cell proliferation, angiogenesis, and tumorigenesis in vertebrates. Although homologs of this gene can be found in plants, the function of MIF in plants remains obscure. Here, we characterized MIF1 in resembling the MIF secreted from . Transcript analysis revealed that responded to stripe rust infection of wheat and was upregulated during the infection stage. MIF1 was localized to both the cytosol and nuclei in wheat mesophyll protoplast. Additionally, MIF1 possessed significant tautomerase activity, indicating conservation of MIFs across kingdoms. infiltration assay demonstrated that MIF1 was capable of suppressing programmed cell death hinting its role in plant immunity. Heterologous expression of MIF1 increased fission yeast sensitivity to oxidative stress. Silencing decreased the susceptibility of wheat to seemingly through increasing reactive oxygen species accumulation. In conclusion, functions of the MIF1 were investigated in this study, which provides significant insight into understanding the role of MIFs across kingdoms.
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http://dx.doi.org/10.3390/biology10090878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470491PMC
September 2021

Ferrocene-Induced Perpetual Recovery on All Elemental Defects in Perovskite Solar Cells.

Angew Chem Int Ed Engl 2021 Nov 21;60(48):25567-25574. Epub 2021 Oct 21.

Key Laboratory of Flexible Electronics (KLOFE) & Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing Tech University (NanjingTech), Nanjing, Jiangsu, 211816, China.

Lead halide perovskites always emerge complex interactions among different elemental ions, which lead to multiple intrinsic imperfections. Elemental defects, such as amine, Pb, and I vacancies at A-, B-, and X-sites, are main issues to deteriorate perovskite solar cells (PSCs). Unfortunately, most previous passivators can only temporarily fix partial inactive vacancies as sacrificial agents. Herein, we propose a recovery agent, ferrocene (Fc), which can form a one-dimensional perovskite with adequate steric cavities and suitable dissociation energy to recover all elemental defects back to active light-harvesting perovskites, and regenerate Fc itself meanwhile. Based on this perpetual chain-reaction cycle, corresponding PSCs maintain >10 000-hour lifetime in inert condition and >1000-hour durabilities under various extreme environments, including continuous 85 °C heating, 50 % relative humidity wetting, and 1-sun light soaking.
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http://dx.doi.org/10.1002/anie.202112074DOI Listing
November 2021

INK4 tumor suppressor proteins mediate resistance to CDK4/6 kinase inhibitors.

Cancer Discov 2021 Sep 20. Epub 2021 Sep 20.

Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center

Cyclin-dependent kinases 4 and 6 (CDK4/6), represent a major therapeutic vulnerability for breast cancer. The kinases are clinically targeted via ATP competitive inhibitors (CDK4/6i); however, drug resistance commonly emerges over time. To understand CDK4/6i resistance, we surveyed over 1,300 breast cancers and identify several genetic alterations (e.g. FAT1, PTEN or ARID1A loss) converging on upregulation of CDK6. Mechanistically, we demonstrate CDK6 causes resistance by inducing and binding CDK inhibitor INK4 proteins (e.g. p18INK4C). In vitro binding and kinase assays together with physical modeling reveal that the p18INK4C/D-cyclin/CDK6 complex occludes CDK4/6i binding while only weakly suppressing ATP binding. Suppression of INK4 expression or its binding to CDK6 restores CDK4/6i sensitivity. To overcome this constraint, we developed bifunctional degraders conjugating palbociclib with E3 ligands. Two resulting lead compounds potently degraded CDK4/6, leading to substantial antitumor effects in vivo, demonstrating the promising therapeutic potential for retargeting CDK4/6 despite CDK4/6i resistance.
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http://dx.doi.org/10.1158/2159-8290.CD-20-1726DOI Listing
September 2021

Umbrella Review on Associations Between Single Nucleotide Polymorphisms and Lung Cancer Risk.

Front Mol Biosci 2021 3;8:687105. Epub 2021 Sep 3.

Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China.

The aim is to comprehensively and accurately assess potential relationships between single nucleotide polymorphisms (SNP) and lung cancer (LC) risk by summarizing the evidence in systematic reviews and meta-analyses. This umbrella review was registered with the PROSPERO international prospective register of systematic reviews under registration number CRD42020204685. The PubMed, Web of Science, and Embase databases were searched to identify eligible systematic reviews and meta-analyses from inception to August 14, 2020. The evaluation of cumulative evidence was conducted for associations with nominally statistical significance based on the Venice criteria and false positive report probability (FPRP). This umbrella review finally included 120 articles of a total of 190 SNP. The median number of studies and sample size included in the meta-analyses were five (range, 3-52) and 4 389 (range, 354-256 490), respectively. A total of 85 SNP (in 218 genetic models) were nominally statistically associated with LC risk. Based on the Venice criteria and FPRP, 13 SNP (in 22 genetic models), 47 SNP (in 99 genetic models), and 55 SNP (in 94 genetic models) had strong, moderate, and weak cumulative evidence of associations with LC risk, respectively. In conclusion, this umbrella review indicated that only 13 SNP (of 11 genes and one miRNA) were strongly correlated to LC risk. These findings can serve as a general and helpful reference for further genetic studies.
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http://dx.doi.org/10.3389/fmolb.2021.687105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8446528PMC
September 2021

Ambient air pollution and COVID-19 risk: Evidence from 35 observational studies.

Environ Res 2021 Sep 15;204(Pt B):112065. Epub 2021 Sep 15.

Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, Liaoning, 110004, China. Electronic address:

Background And Aims: The coronavirus disease 2019 (COVID-19) pandemic is severely threatening and challenging public health worldwide. Epidemiological studies focused on the influence of outdoor air pollution (AP) on COVID-19 risk have produced inconsistent conclusions. We aimed to quantitatively explore this association using a meta-analysis.

Methods: We searched for studies related to outdoor AP and COVID-19 risk in the Embase, PubMed, and Web of Science databases. No language restriction was utilized. The search date entries were up to August 13, 2021. Pooled estimates and 95% confidence intervals (CIs) were obtained with random-/fixed-effects models. PROSPERO registration number: CRD42021244656.

Results: A total of 35 articles were eligible for the meta-analysis. For long-term exposure to AP, COVID-19 incidence was positively associated with 1 μg/m increase in nitrogen dioxide (NO; effect size = 1.042, 95% CI 1.017-1.068), particulate matter with diameter <2.5 μm (PM; effect size = 1.056, 95% CI 1.039-1.072), and sulfur dioxide (SO; effect size = 1.071, 95% CI 1.002-1.145). The COVID-19 mortality was positively associated with 1 μg/m increase in nitrogen dioxide (NO; effect size = 1.034, 95% CI 1.006-1.063), PM (effect size = 1.047, 95% CI 1.025-1.1071). For short-term exposure to air pollutants, COVID-19 incidence was positively associated with 1 unit increase in air quality index (effect size = 1.001, 95% CI 1.001-1.002), 1 μg/m increase NO (effect size = 1.014, 95% CI 1.011-1.016), particulate matter with diameter <10 μm (PM; effect size = 1.005, 95% CI 1.003-1.008), PM (effect size = 1.003, 95% CI 1.002-1.004), and SO (effect size = 1.015, 95% CI 1.007-1.023).

Conclusions: Outdoor air pollutants are detrimental factors to COVID-19 outcomes. Measurements beneficial to reducing pollutant levels might also reduce the burden of the pandemic.
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http://dx.doi.org/10.1016/j.envres.2021.112065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440008PMC
September 2021

Validity of the food frequency questionnaire for adults in nutritional epidemiological studies: A systematic review and meta-analysis.

Crit Rev Food Sci Nutr 2021 Sep 14:1-19. Epub 2021 Sep 14.

Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China.

As the most widely used tool for assessing dietary intake, the validity of food frequency questionnaires (FFQs) should be evaluated before application. A comprehensive search of the PubMed and Web of Science databases was conducted for publications from January 2000 to April 1, 2020. Pooled estimates were calculated for correlation coefficients and mean differences for energy and 61 nutrients between FFQs and standard methods. The literature search identified 130 articles that included 21,494 participants. Subgroup analyses according to the number of administrations of the reference method, sample size, administration methods, FFQ items, reference periods, quality of the studies, gender, and regions were also performed. We conducted a meta-analysis by summarizing the available evidence to comprehensively assess the validity of FFQs stratified by the reference method type (24-hour recall (24HRs) and food records (FRs). We also performed subgroup analyses to examine the impact on the final summary estimates. After a meta-analysis of the FFQs' validity correlation coefficients of the included studies, this study showed that the range (median) of the validity coefficients of the 24HRs as reference methods was 0.220-0.770 (0.416), and for the FRs, it was 0.173-0.735 (0.373), which indicated that FFQs were suitable to assess the overall dietary intake in nutritional epidemiological studies. The results of the subgroup analysis showed that the number of administrations of the reference method, administration mode, number of items, reference periods, sample size, and gender mainly affected the validity correlation of FFQs.Supplemental data for this article is available online at https://doi.org/10.1080/10408398.2021.1966737 .
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http://dx.doi.org/10.1080/10408398.2021.1966737DOI Listing
September 2021

The economic benefits of increased sugar-free chewing gum in China: a budget impact analysis.

BMC Oral Health 2021 09 7;21(1):436. Epub 2021 Sep 7.

Department of Preventive Dentistry, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, National Clinical Research Center for Oral Diseases, Research Center of Engineering and Technology for Digital Dentistry of Ministry of Health, Peking University School and Hospital of Stomatology, Beijing, 100081, China.

Background: To analyze the potential cost savings in dental care associated with increased sugar-free gum (SFG) use among Chinese teenagers and adults.

Methods: The amount of SFG chewed per year and decayed, missing and filled teeth (DMFT) was collected from a cross-sectional survey to create a dose-response curve assumption. A cost analysis of dental restoration costs was carried out. A budget impact analysis was performed to model the decrease in DMFT and the subsequent cost savings for dental care. Three different scenarios for the increase in the number of SFG were calculated.

Results: The average cost savings per person in the Chinese population due to increasing SFG use ranged from 45.95 RMB (6.94 USD) per year to 67.41 RMB (10.19 USD) per year. It was estimated that 21.51-31.55 billion RMB (3.25-4.77 billion USD) could be saved annually if all SFG chewers among Chinese teenagers and adults chewed SFG regularly.

Conclusion: This study suggests that dental care costs could be significantly reduced if SFG use increased in the Chinese population.
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http://dx.doi.org/10.1186/s12903-021-01786-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424996PMC
September 2021

Threshold thickness of foveal outer nuclear layer associated with outcomes of photodynamic therapy in central serous chorioretinopathy.

Eye (Lond) 2021 Sep 3. Epub 2021 Sep 3.

Department of Ophthalmology, Fudan University Eye Ear Nose and Throat Hospital, Shanghai, China.

Objectives: To investigate the threshold thickness of the foveal outer nuclear layer (ONL) associated with favourable visual outcome after half-dose photodynamic therapy (PDT) in patients with central serous chorioretinopathy (CSC).

Methods: The CSC patients were divided into two groups according to whether their best-corrected visual acuity (BCVA) at 1 year after half-dose PDT was 20/20 or worse than 20/20. Three multivariable logistic regression models were respectively created to determine the prognostic value of the pre-PDT foveal ONL thickness, the pre- and the post-PDT foveal ONL thickness ratio, which was defined as the foveal ONL thickness in the CSC eye to that in the normal contralateral eye, for predicting the outcome of half-dose PDT. The areas under the receiver operating characteristic curves (AUCs) were compared and the best cut-off values were determined, respectively.

Results: Totally, 134 patients were included. The pre-PDT foveal ONL thickness, the pre-PDT and the post-PDT foveal ONL thickness ratios were all independent predictors of the outcome after half-dose PDT in their respective model (all P < 0.05). The AUC of the post-PDT foveal ONL thickness ratio was significantly higher than the AUCs of the other two parameters (0.940 vs 0.840 and 0.882, DeLong test: both P < 0.05), with the cut-off value of 0.81.

Conclusions: The threshold of the foveal ONL thickness ratio is 0.81. Active CSC eyes with a foveal ONL thickness ratio of 0.81 or more could probably retain BCVA of 20/20 after half-dose PDT. They were considered reasonable to wait for spontaneous resolution of sub-retinal fluid.
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http://dx.doi.org/10.1038/s41433-021-01762-0DOI Listing
September 2021

P4HA2-induced prolyl hydroxylation suppresses YAP1-mediated prostate cancer cell migration, invasion, and metastasis.

Oncogene 2021 Oct 1;40(41):6049-6056. Epub 2021 Sep 1.

Department of Genitourinary Medical Oncology and the David H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Yes-associated protein 1 (YAP1), a key player in the Hippo pathway, has been shown to play a critical role in tumor progression. However, the role of YAP1 in prostate cancer cell invasion, migration, and metastasis is not well defined. Through functional, transcriptomic, epigenomic, and proteomic analyses, we showed that prolyl hydroxylation of YAP1 plays a critical role in the suppression of cell migration, invasion, and metastasis in prostate cancer. Knockdown (KD) or knockout (KO) of YAP1 led to an increase in cell migration, invasion, and metastasis in prostate cancer cells. Microarray analysis showed that the EMT pathway was activated in Yap1-KD cells. ChIP-seq analysis showed that YAP1 target genes are enriched in pathways regulating cell migration. Mass spectrometry analysis identified P4H prolyl hydroxylase in the YAP1 complex and YAP1 was hydroxylated at multiple proline residues. Proline-to-alanine mutations of YAP1 isoform 3 identified proline 174 as a critical residue, and its hydroxylation suppressed cell migration, invasion, and metastasis. KO of P4ha2 led to an increase in cell migration and invasion, which was reversed upon Yap1 KD. Our study identified a novel regulatory mechanism of YAP1 by which P4HA2-dependent prolyl hydroxylation of YAP1 determines its transcriptional activities and its function in prostate cancer metastasis.
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http://dx.doi.org/10.1038/s41388-021-02000-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8526415PMC
October 2021
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