Publications by authors named "Ye He"

166 Publications

The lungs were on fire: a pilot study of F-FDG PET/CT in idiopathic-inflammatory-myopathy-related interstitial lung disease.

Arthritis Res Ther 2021 Jul 23;23(1):198. Epub 2021 Jul 23.

Department of Rheumatology, The First Affiliated Hospital, Zhejiang University School of Medicine, #79 Qingchun Road, Hangzhou, 310003, Zhejiang Province, People's Republic of China.

Background: Interstitial lung disease (ILD) and its rapid progression (RP) are the main contributors to unfavourable outcomes of patients with idiopathic inflammatory myopathy (IIM). This study aimed to identify the clinical value of PET/CT scans in IIM-ILD patients and to construct a predictive model for RP-ILD.

Methods: Adult IIM-ILD patients who were hospitalized at four divisions of the First Affiliated Hospital, Zhejiang University School of Medicine (FAHZJU), from 1 January 2017 to 31 December 2020 were reviewed. PET/CT scans and other characteristics of patients who met the inclusion and exclusion criteria were collected and analysed.

Results: A total of 61 IIM-ILD patients were enrolled in this study. Twenty-one patients (34.4%) developed RP-ILD, and 24 patients (39.3%) died during follow-up. After false discovery rate (FDR) correction, the percent-predicted diffusing capacity of the lung for carbon monoxide (DLCO%, P = 0.014), bilateral lung mean standard uptake value (SUVmean, P = 0.014) and abnormal mediastinal lymph node (P = 0.045) were significantly different between the RP-ILD and non-RP-ILD groups. The subsequent univariate and multivariate logistic regression analyses verified our findings. A "DLM" model was established by including the above three values to predict RP-ILD with a cut-off value of ≥ 2 and an area under the curve (AUC) of 0.905. Higher bilateral lung SUVmean (P = 0.019) and spleen SUVmean (P = 0.011) were observed in IIM-ILD patients who died within 3 months, and a moderate correlation was recognized between the two values.

Conclusions: Elevated bilateral lung SUVmean, abnormal mediastinal lymph nodes and decreased DLCO% were significantly associated with RP-ILD in IIM-ILD patients. The "DLM" model was valuable in predicting RP-ILD and requires further validation.
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http://dx.doi.org/10.1186/s13075-021-02578-9DOI Listing
July 2021

Doping and facet effects synergistically mediated interfacial reaction mechanism and selectivity in photocatalytic NO abatement.

J Colloid Interface Sci 2021 Jul 9;604:624-634. Epub 2021 Jul 9.

Yangtze Delta Region Institute (Huzhou) & School of Resources and Environment, University of Electronic Science and Technology of China, Huzhou 313001, China. Electronic address:

The surface atomic coordination and arrangement largely determine photocatalytic properties. Whereas, the intrinsic impact of surface microstructures on the reaction mechanism and pathway is still unclear. Herein, via constructing N-doped BiOCO photocatalysts with diverse exposed facets, (1 1 0) and (0 0 1) facet, we testify that the pivotal roles of crystal facet and doping effect on the intermediate production and reactivity for photocatalytic nitric oxide (NO) abatement. The photoreactivity of N-doped BiOCO is documented to be higher than that of the pure samples because of the enhanced light absorption and charge transfer. Further in situ probing experiments and theoretical calculations verify that the unique adsorption patterns and activated intermediates on the (1 1 0) facet facilitate the formation of final products and inhibit the generation of toxic NO by-product in terms of thermodynamics. More importantly, we found that the selective and nonselective oxidation processes are emerged over (1 1 0) and (0 0 1) facets of BiOCO, respectively.
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http://dx.doi.org/10.1016/j.jcis.2021.07.018DOI Listing
July 2021

Crystal-structure dependent reaction pathways in photocatalytic formaldehyde mineralization on BiPO.

J Hazard Mater 2021 Jul 13;420:126633. Epub 2021 Jul 13.

School of Resources and Environment, University of Electronic Science and Technology of China, Chengdu 611731, China; Yangtze Delta Region Institute (Huzhou), University of Electronic Science and Technology of China, Huzhou 313001, China. Electronic address:

Formaldehyde as significant environmental hazard in air seriously harm the environment and human health. Although photocatalysis has demonstrated the possibility for HCHO degradation, it has long been limited by unsatisfied degradation efficiency and the unclear reaction mechanism. Here, we confirm that surface atomic arrangement of BiPO plays a critical role in photooxidation of HCHO via modulating the reaction pathway, offering 2.63 times enhancement of HCHO degradation efficiency. We dissect the processes in the photocatalytic reaction by DFT calculation, ROS monitoring, and in situ diffuse reflectance infrared Fourier transform spectra (DRIFTS) investigation. Specifically, we reveal that the controlling surface atomic arrangement could modulate adsorption model from single-point to bridging, and promote activation of small molecules. Concurrently, the active surface dependent on crystal structure facilitates the efficient transformation of intermediates (HCOOH*) (reducing energy barrier from 0.41 to -0.35 eV), producing final-product (HCO, ∆G = -0.35 eV) while suppressing toxic by-product (CO, ∆G = 0.32 eV), which contributes to the sustained deep mineralization of HCHO with enhancement by 61.4%. The findings are crucial as they provide crystal-structure related insights into the design of efficient catalysts for photocatalytic HCHO degradation. Ultimately, current molecular understanding should unlock the solar-driven catalytic pathways for other oxidation reactions.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126633DOI Listing
July 2021

Early Postnatal Oxygen Exposure Predicts Choroidal Thinning in Neonates.

Invest Ophthalmol Vis Sci 2021 Jul;62(9):23

Department of Pediatrics, Division of Neonatology and Developmental Biology, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California, United States.

Purpose: To evaluate whether choroidal thickness (CT) using arm-mounted optical coherence tomography (OCT) in infants screened for retinopathy of prematurity (ROP) correlates with oxygen exposure in neonates.

Methods: OCT images were obtained in infants screened for ROP in a single level IV neonatal intensive care unit. CT was measured at three different locations: the subfoveal center and 1.5 mm from the fovea center in each direction. Correlation and regression analyses were performed to determine the relationship between clinical factors and CT. Clinical factors included gestational age, birth weight, presence of bronchopulmonary dysplasia (BPD), and fraction of inspired oxygen (FiO2) at defined time points: 30 weeks postmenstrual age (PMA), 36 weeks PMA, and on day of imaging.

Results: Mean subfoveal, nasal, and temporal choroidal thicknesses CT (SFCT, NCT, and TCT, respectively) were 228.0 ± 51.4 µm, 179.7 ± 50.3 µm, and 186.4 ± 43.8 µm, respectively. SFCT was found to be significantly thicker than NCT and TCT (P < 0.0001 and P = 0.0002, respectively), but no significant difference was found between NCT and TCT (P = 0.547). Compared with infants without BPD, infants with BPD had thinner SFCT and NCT (P = 0.01 and P = 0.0008, respectively). Birth weight was positively correlated with SFCT (r = 0.39, P = 0.01) and NCT (r = 0.33, P = 0.045) but not TCT. Gestational age and ROP stage were not significantly associated with CT. SFCT was found to be significantly thinner with higher average FiO2 supplementation levels at 30 weeks PMA (r = -0.51, P = 0.01) but not at 36 weeks PMA. Regression analysis revealed that FiO2 at 30 weeks PMA was an independent predictor of SFCT in infants screened for ROP (P = 0.01).

Conclusions: Early postnatal exposure (<32 weeks PMA) to higher oxygen supplementation in premature neonates statistically predicts choroidal thinning.
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http://dx.doi.org/10.1167/iovs.62.9.23DOI Listing
July 2021

The Atr-Chek1 pathway inhibits axon regeneration in response to Piezo-dependent mechanosensation.

Nat Commun 2021 06 22;12(1):3845. Epub 2021 Jun 22.

Raymond G. Perelman Center for Cellular and Molecular Therapeutics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.

Atr is a serine/threonine kinase, known to sense single-stranded DNA breaks and activate the DNA damage checkpoint by phosphorylating Chek1, which inhibits Cdc25, causing cell cycle arrest. This pathway has not been implicated in neuroregeneration. We show that in Drosophila sensory neurons removing Atr or Chek1, or overexpressing Cdc25 promotes regeneration, whereas Atr or Chek1 overexpression, or Cdc25 knockdown impedes regeneration. Inhibiting the Atr-associated checkpoint complex in neurons promotes regeneration and improves synapse/behavioral recovery after CNS injury. Independent of DNA damage, Atr responds to the mechanical stimulus elicited during regeneration, via the mechanosensitive ion channel Piezo and its downstream NO signaling. Sensory neuron-specific knockout of Atr in adult mice, or pharmacological inhibition of Atr-Chek1 in mammalian neurons in vitro and in flies in vivo enhances regeneration. Our findings reveal the Piezo-Atr-Chek1-Cdc25 axis as an evolutionarily conserved inhibitory mechanism for regeneration, and identify potential therapeutic targets for treating nervous system trauma.
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http://dx.doi.org/10.1038/s41467-021-24131-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219705PMC
June 2021

Transplantation of reprogrammed peripheral blood cells differentiates into retinal ganglion cells in the mouse eye with NMDA-induced injury.

J Cell Physiol 2021 Jun 8. Epub 2021 Jun 8.

Hunan Key Laboratory of Ophthalmology, Eye Center of Xiangya Hospital, Central South University, Changsha, Hunan, China.

The generation of patient-specific induced pluripotent stem cells (iPSCs) holds significant implications for replacement therapy in treating optic neuropathies such as glaucoma. Stem-cell-based therapy targeted at replacing and replenishing retinal ganglion cells is progressing at a fast pace. However, clinical application necessitates an efficient and robust approach for cell manufacturing. Here, we examine whether the embryo body derived from human peripheral blood-derived iPSC can localize into the host retina and differentiate into retinal ganglion cells after transplantation into a glaucoma injury model. Human peripheral blood T cells were isolated and reprogrammed into an induced pluripotent stem cell (TiPSC) line using Sendai virus transduction carrying transcription factors Sox2, Klf4, c-Myc, and Oct4. TiPSCs were differentiated into RGC using neural basal culture. For in vivo studies, embryo bodies derived from TiPSCs (TiPSC-EB) were injected into the vitreous cavity of N-Methyl-d-aspartic acid (NMDA)-treated mice 2 weeks before sacrifice and retinal dissection. Induced pluripotent stem cells generated from human peripheral blood T cells display stem cell morphology and pluripotency markers. Furthermore, RGC-like cells differentiated from TiPSC exhibit extending axons and RGC marker TUJ1. When transplanted intravitreally into NMDA-treated mice, embryo bodies derived from TiPSC survived, migrated, and incorporated into the retina's GCL layer. In addition, TiPSC-EB transplants were able to differentiate into TUJ1 positive RGC-like cells. Retinal ganglion cells can be differentiated using human peripheral blood cells derived iPSC. Transplantation of embryo body derived from TiPSCs into a glaucoma mouse model could incorporate into host GCL and differentiate into RGC-like cells.
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http://dx.doi.org/10.1002/jcp.30464DOI Listing
June 2021

Enzymatically-degradable hydrogel coatings on titanium for bacterial infection inhibition and enhanced soft tissue compatibility a self-adaptive strategy.

Bioact Mater 2021 Dec 19;6(12):4670-4685. Epub 2021 May 19.

Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400044, China.

Ideal percutaneous titanium implants request both antibacterial ability and soft tissue compatibility. ZnO structure constructed on titanium has been widely proved to be helpful to combat pathogen contamination, but the biosafety of ZnO is always questioned. How to maintain the remarkable antibacterial ability of ZnO and efficiently reduce the corresponding toxicity is still challenging. Herein, a hybrid hydrogel coating was constructed on the fabricated ZnO structure of titanium, and the coating was proved to be enzymatically-degradable when bacteria exist. Then the antibacterial activity of ZnO was presented. When under the normal condition (no bacteria), the hydrogel coating was stable and tightly adhered to titanium. The toxicity of ZnO was reduced, and the viability of fibroblasts was largely improved. More importantly, the hydrogel coating provided a good buffer zone for cell ingrowth and soft tissue integration. The curbed Zn ion release was also proved to be useful to regulate fibroblast responses such as the expression of CTGF and COL-I. These results were also validated by studies. Therefore, this study proposed a valid self-adaptive strategy for ZnO improvement. Under different conditions, the sample could present different functions, and both the antibacterial ability and soft tissue compatibility were finely preserved.
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http://dx.doi.org/10.1016/j.bioactmat.2021.05.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164017PMC
December 2021

Brain-specific lipoprotein receptors interact with astrocyte derived apolipoprotein and mediate neuron-glia lipid shuttling.

Nat Commun 2021 04 23;12(1):2408. Epub 2021 Apr 23.

Dendrite Morphogenesis and Plasticity Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.

Lipid shuttling between neurons and glia contributes to the development, function, and stress responses of the nervous system. To understand how a neuron acquires its lipid supply from specific lipoproteins and their receptors, we perform combined genetic, transcriptome, and biochemical analyses in the developing Drosophila larval brain. Here we report, the astrocyte-derived secreted lipocalin Glial Lazarillo (GLaz), a homolog of human Apolipoprotein D (APOD), and its neuronal receptor, the brain-specific short isoforms of Drosophila lipophorin receptor 1 (LpR1-short), cooperatively mediate neuron-glia lipid shuttling and support dendrite morphogenesis. The isoform specificity of LpR1 defines its distribution, binding partners, and ability to support proper dendrite growth and synaptic connectivity. By demonstrating physical and functional interactions between GLaz/APOD and LpR1, we elucidate molecular pathways mediating lipid trafficking in the fly brain, and provide in vivo evidence indicating isoform-specific expression of lipoprotein receptors as a key mechanism for regulating cell-type specific lipid recruitment.
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http://dx.doi.org/10.1038/s41467-021-22751-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065144PMC
April 2021

Association Between a Tri-allelic Polymorphism in the Estrogen Metabolism Oxidoreductase NRH:Quinone Oxidoreductase 2 Gene and Risk of Breast Cancer by Molecular Subtype.

Front Genet 2021 12;12:658285. Epub 2021 Mar 12.

Department of Breast Surgery, Fudan University Shanghai Cancer Center and Cancer Institute, Shanghai Medical College, Fudan University, Shanghai, China.

: We hypothesized that NRH:quinone oxidoreductase 2 (NQO2) is a candidate susceptibility gene for breast cancer because of its known enzymatic activity on estrogen-derived quinones. A tri-allelic polymorphism in the NQO2 gene might be associated with the risk of luminal-like breast cancer. : In this case-control study, 2,865 women were recruited, including 1,164 patients with pathologically confirmed breast cancer and 1,701 cancer-free controls. The tri-allelic genetic polymorphism (I-29, I-16, and D alleles) was genotyped by a polymerase chain reaction and restriction fragment length polymorphism (RFLP)-based assay. Because the I-16 allele frequency is rare (approximately 1.0%), individuals carrying the I-16 allele were excluded from the analysis. Breast cancer subtypes were classified according to ER, PR, HER2, and grade. : In the association analysis of allele, an increased risk of breast cancer is associated with I-29 allele [82.5% in case group and 79.0% in the control group; odds ratio (OR), 1.25; 95% CI, 1.09-1.43, compared with D allele, = 0.0015]. In the association analysis of genotype, the I-29-containing genotype was significantly correlated with breast cancer under a dominant model (adjusted OR, 1.31, 95% CI, 1.12-1.54, = 0.001). Moreover, in the subtype analysis, there was a significant association of the I-29/D polymorphism with luminal-like breast cancer (adjusted OR, 1.54, 95% CI, 1.22-1.94, = 0.001 for luminal-A disease; adjusted OR, 1.37, 95% CI, 1.06-1.76, = 0.014 for luminal-B disease) but not with HER2-enriched or triple-negative subtypes. : The tri-allelic polymorphism in the NQO2 gene is associated with breast cancer risk, especially for the luminal-like subtype. Our findings provide a new piece of molecular epidemical evidence supporting the hypothesis that estrogen and its metabolites are carcinogens of luminal-like breast cancer. Further external validation studies are needed.
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http://dx.doi.org/10.3389/fgene.2021.658285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994273PMC
March 2021

CXC Chemokines as Therapeutic Targets and Prognostic Biomarkers in Skin Cutaneous Melanoma Microenvironment.

Front Oncol 2021 9;11:619003. Epub 2021 Mar 9.

Hunan Key Laboratory of Ophthalmology, Eye Center of Xiangya Hospital, Central South University, Changsha, China.

Background: Skin Cutaneous Melanoma (SKCM) is a tumor of the epidermal melanocytes induced by gene activation or mutation. It is the result of the interaction between genetic, constitutional, and environmental factors. SKCM is highly aggressive and is the most threatening skin tumor. The incidence of the disease is increasing year by year, and it is the main cause of death in skin tumors around the world. CXC chemokines in the tumor microenvironment can regulate the transport of immune cells and the activity of tumor cells, thus playing an anti-tumor immunological role and affecting the prognosis of patients. However, the expression level of CXC chemokine in SKCM and its effect on prognosis are still unclear.

Method: Oncomine, UALCAN, GEPIA, STRING, GeneMANIA, cBioPortal, TIMER, TRRUST, DAVID 6.8, and Metascape were applied in our research.

Result: The transcription of CXCL1, CXCL5, CXCL8, CXCL9, CXCL10, and CXCL13 in SKCM tissues were significantly higher than those in normal tissues. The pathological stage of SKCM patients is closely related to the expression of CXCL4, CXCL9, CXCL10, CXCL11, CXCL12, and CXCL13. The prognosis of SKCM patients with low transcription levels of CXCL4, CXCL9, CXCL10, CXCL11, and CXCL13 is better. The differential expression of CXC chemokines is mainly associated with inflammatory response, immune response, and cytokine mediated signaling pathways. Our data indicate that the key transcription factors of CXC chemokines are RELA, NF-κB1 and SP1. The targets of CXC chemokines are mainly LCK, LYN, SYK, MAPK2, MAPK12, and ART. The relationship between CXC chemokine expression and immune cell infiltration in SKCM was closed.

Conclusions: Our research provides a basis for screening SKCM biomarkers, predicting prognosis, and choosing immunotherapy.
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http://dx.doi.org/10.3389/fonc.2021.619003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985846PMC
March 2021

No significant long-term complications from inadvertent exposure to gonadotropin-releasing hormone agonist during early pregnancy in mothers and offspring: a retrospective analysis.

Reprod Biol Endocrinol 2021 Mar 20;19(1):46. Epub 2021 Mar 20.

Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, 230022, China.

Background: Administration of gonadotropin-releasing hormone agonist (GnRH-a) in the luteal phase is commonly used for pituitary suppression during in vitro fertilisation (IVF). There is an ineluctable risk of inadvertent exposure of spontaneous pregnancy to GnRH-a. However, little is known about the pregnancy complications and repregnancy outcomes of the affected women and the neurodevelopmental outcomes of the GnRH-a-exposed children.

Methods: Retrospective analysis was used to determine obstetric and repregnancy outcomes after natural conception in 114 women who naturally conceived while receiving GnRH-a during their early pregnancy over the past 17 years. The GnRH-a-exposed children were evaluated to determine their neonatal characteristics and long-term neurodevelopmental outcomes. The outcomes were compared to those of relevant age-matched control groups.

Results: Sixty-five women had 66 live births. The neonatal health outcomes and the incidence of maternal complications were similar in the GnRH-a-exposed and control groups. Thirty-one GnRH-a-exposed children, aged 2-8 years, were available for investigation of neurodevelopment. Except for one case of autism spectrum disorder, the full-scale intelligence quotient score was within the normal range and similar to that of the control group. Most mothers with successful pregnancies and about one-third of the women who had spontaneous abortions were subsequently able to conceive naturally again. IVF is recommended for repregnancy in women who have experienced ectopic pregnancies.

Conclusions: Accidental exposure to GnRH-a in early pregnancy might be safe. Reproductive treatment suggestions for repregnancy should be made with consideration of the outcomes of the previously GnRH-a-exposed spontaneous pregnancy.
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http://dx.doi.org/10.1186/s12958-021-00732-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7980339PMC
March 2021

Genesis, controls and risk prediction of HS in coal mine gas.

Sci Rep 2021 Mar 11;11(1):5712. Epub 2021 Mar 11.

School of Resources and Earth Geosciences, China University of Mining and Technology, Jiangsu, Xuzhou, 221116, China.

Abnormal HS concentration in coal mine gas is a serious threat to normal mining activities, which has caused serious loss of life and property in many coal mines. This study explores the genesis and influencing factors of abnormal HS concentration in coal mine gas, taking the Xishan coal mine in the Fukang mining area as a case study. The HS formation by bacterial sulfate reduction (BSR) is simulated with a bacterial culture experiment and that by thermochemical sulfate reduction (TSR) is simulated with a thermal reduction experiment. The potential for a magmatic genesis is assessed using data regarding the tectonic evolution and history of magma intrusion in the study area. The factors influencing HS formation and enrichment are then analyzed by a comprehensive consideration of the characteristics of coal, the gas composition, the coal seam groundwater geochemistry and other geological factors in the study area. The results show that the study area meets the necessary conditions for the BSR process to operate and that there is widespread BSR derived HS. TSR genesis HS mainly forms in coal fire areas and their vicinity, while there is little contribution from magmatically formed HS. The concentration of HS is negatively correlated with the buried depth of the coal seam, the concentrations of CH, N and CO, and the ash yield; and it is positively correlated with the volatiles yield and total sulfur content. In addition, in areas with abnormally high HS concentration, the concentration of SO is obviously lower, HCO + CO concentration is higher, and the HCO/SO value is larger than that in non-anomalous areas. Geologically, HS enrichment is found to be controlled by lithology, tectonism, and hydrogeological conditions. Moreover, the results of predictive modeling show that areas prone to abnormal HS concentration are generally spatially correlated with coal fire areas. In this study, the genetic types of HS and the factors controlling their formation and retention are discussed, producing research results that have guiding significance for the prediction and prevention of the coal mine disasters that arises from abnormal HS concentration.
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http://dx.doi.org/10.1038/s41598-021-85263-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970972PMC
March 2021

Near-Infrared Light-Activatable Dual-Action Nanoparticle Combats the Established Biofilms of Methicillin-Resistant Staphylococcus aureus and Its Accompanying Inflammation.

Small 2021 04 10;17(13):e2007522. Epub 2021 Mar 10.

Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing, 400044, P. R. China.

Clinically, inhibition of both bacterial infection and excessive inflammation is a crucial step for improved wound treatments. Herein, the fabrication of near-infrared-light (NIR)-activatable deoxyribonuclease (DNase)-carbon monoxide (CO)@mesoporous polydopamine nanoparticles (MPDA NPs) is demonstrated for efficient elimination of methicillin-resistant Staphylococcus aureus (MRSA) biofilms and the following anti-inflammatory activity. Specifically, thermosensitive CO-gas-releasing donors (CO releasing molecules, FeCO) are first encapsulated into MPDA NPs, followed by covalently immobilizing deoxyribonuclease I (DNase I) on the surfaces of MPDA NPs. DNase I can degrade the extracellular DNA in biofilms, which site specifically destroys the compactness of the biofilms. With NIR irradiation, [email protected] NPs display great photothermal ability, and further trigger on-demand delivery of bactericidal CO gas that can adequately permeate the impaired biofilms. Eventually, they achieve effective MRSA biofilm elimination in virtue of the synergistic effects of both DNase I participation and CO-gas-potentiated photothermal therapy. Importantly, the inflammatory responses of [email protected] NPs and NIR-treated wounds are simultaneously alleviated owing to the anti-inflammatory features of released CO. Finally, NIR-activatable [email protected] NPs accelerate the healing process of MRSA-biofilm-infected cutaneous wounds. Taken together, this phototherapeutic strategy displays great therapeutic potential in treating the formidable clinical problems caused by MRSA biofilms and the accompanying inflammation.
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http://dx.doi.org/10.1002/smll.202007522DOI Listing
April 2021

Smart Responsive Quercetin-Conjugated Glycol Chitosan Prodrug Micelles for Treatment of Inflammatory Bowel Diseases.

Mol Pharm 2021 03 1;18(3):1419-1430. Epub 2021 Feb 1.

State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing 100029, P. R. China.

The incidence and progression of inflammatory bowel disease are closely related to oxidative stress caused by excessive production of reactive oxygen species (ROS). To develop an efficacious and safe nanotherapy against inflammatory bowel diseases (IBD), we designed a novel pH/ROS dual-responsive prodrug micelle as an inflammatory-targeted drug, which was comprised by active quercetin () covalently linked to biocompatible glycol chitosan () by aryl boronic ester as a responsive linker. The optimized micelles exhibited well-controlled physiochemical properties and stability in a physiological environment. Time-dependent NMR spectra traced the changes in the polymer structure in the presence of HO, confirming the release of the drug. The drug release studies indicated a low release rate (<20 wt %) in physiological conditions, but nearly complete release (>95 wt % after 72 h incubation) in a pH 5.8 medium containing 10 μM HO, exhibiting a pH/ROS dual-responsive property and sustained release behavior. Importantly, the negligible drug release in a simulated gastric environment in 1 h allowed us to perform intragastric administration, which has potential to achieve the oral delivery by mature enteric-coating modification in future. Further activities and biodistribution experiments found that the micelles tended to accumulate in intestinal inflammation sites and showed better therapeutic efficacy than the free drugs (quercetin and mesalazine) in a colitis mice model. Typical inflammatory cytokines including TNF-α, IL-6, and iNOS were significantly suppressed by micelle treatment. Our work promoted inflammatory-targeted delivery and intestinal drug accumulation for active single drug quercetin and improved the therapeutic effect of IBD. The current study also provided an alternative strategy for designing a smart responsive nanocarrier for a catechol-based drug to better achieve the target drug delivery.
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http://dx.doi.org/10.1021/acs.molpharmaceut.0c01245DOI Listing
March 2021

Dihydrotestosterone-induced hair regrowth inhibition by activating androgen receptor in C57BL6 mice simulates androgenetic alopecia.

Biomed Pharmacother 2021 May 29;137:111247. Epub 2021 Jan 29.

Department of Plastic and Aesthetic Surgery Nanfang Hospital of Southern Medical University Guangzhou, Guangdong Province, 510515, China. Electronic address:

Androgenic alopecia (AGA), also known as male pattern baldness, is one of the most common hair loss diseases worldwide. The main treatments of AGA include hair transplant surgery, oral medicines, and LDL laser irradiation, although no treatment to date can fully cure this disease. Animal models play important roles in the exploration of potential mechanisms of disease development and in assessing novel treatments. The present study describes androgen receptor (AR) in C57BL/6 mouse hair follicles that can be activated by dihydrotestosterone (DHT) and translocate to the nucleus. This led to the design of a mouse model of androgen-induced AGA in vivo and in vitro. DHT was found to induce early hair regression, hair miniaturization, hair density loss, and changes in hair morphology in male C57BL/6 mice. These effects of DHT could be partly reversed by the AR antagonist bicalutamide. DHT had similar effects in an ex vivo model of hair loss. Evaluation of histology, organ culture, and protein expression could explain the mechanism by which DHT delayed hair regrowth.
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http://dx.doi.org/10.1016/j.biopha.2021.111247DOI Listing
May 2021

Melanin-Inspired Chromophoric Microparticles Composed of Polymeric Peptide Pigments.

Angew Chem Int Ed Engl 2021 03 24;60(14):7564-7569. Epub 2021 Feb 24.

Advanced Science Research Center (ASRC) at the Graduate Center, City University of New York (CUNY), 85 St Nicholas Terrace, New York, NY, 10031, USA.

Melanin and related polyphenolic pigments are versatile functional polymers that serve diverse aesthetic and protective roles across the living world. These polymeric pigments continue to inspire the development of adhesive, photonic, electronic and radiation-protective materials and coatings. The properties of these structures are dictated by covalent and non-covalent interactions in ways that, despite progress, are not fully understood. It remains a major challenge to direct oxidative polymerization of their precursors (amino acids, (poly-)phenols, thiols) toward specific structures. By taking advantage of supramolecular pre-organization of tyrosine-tripeptides and reactive sequestering of selected amino acids during enzymatic oxidation, we demonstrate the spontaneous formation of distinct new chromophores with optical properties that are far beyond the range of those found in biological melanins, in terms of color, UV absorbance and fluorescent emission.
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http://dx.doi.org/10.1002/anie.202015170DOI Listing
March 2021

Sample Preparation for Metabolic Profiling using MALDI Mass Spectrometry Imaging.

J Vis Exp 2020 12 22(166). Epub 2020 Dec 22.

The Graduate Center - Advanced Science Research Center, Neuroscience Initiative, The City University of New York; The Graduate Center - Advanced Science Research Center, MALDI MS Imaging Joint Core Facility, The City University of New York;

Metabolomics, the study to identify and quantify small molecules and metabolites present in an experimental sample, has emerged as an important tool to investigate the biological activities during development and diseases. Metabolomics approaches are widely employed in the study of cancer, nutrition/diet, diabetes, and other physiological and pathological conditions involving metabolic processes. An advantageous tool that aids in metabolomic profiling advocated in this paper is matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI). Its ability to detect metabolites in situ without labeling, structural modifications, or other specialized reagents, such as those used in immunostaining, makes MALDI MSI a unique tool in advancing methodologies relevant in the field of metabolomics. An appropriate sample preparation process is critical to yield optimal results and will be the focus of this paper.
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http://dx.doi.org/10.3791/62008DOI Listing
December 2020

The associations of childhood adiposity with menopausal symptoms in women aged 45-49 years: An Australian Cohort Study.

Maturitas 2021 Jan 1;143:81-88. Epub 2020 Oct 1.

Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia. Electronic address:

Objectives: To examine the associations of childhood adiposity with menopausal symptoms in women aged 45-49 years.

Study Design: National population-based cohort study of 334 girls prospectively followed from childhood (aged 11-15) through to midlife (aged 45-49). Childhood overweight and obesity were defined by international age- and sex-specific standards for body mass index (BMI), and abdominal obesity was defined as waist/height ratio≥0.5.

Main Outcome Measures: Vasomotor symptoms (VMS), vaginal dryness, total menopausal symptoms and domain-specific symptoms (somatic, psychological and urogenital) were measured during 2018-19 using the Menopause Rating Scale (MRS) and classified as none, mild, moderate or severe.

Results: The prevalence of mild, moderate and severe VMS was 24.0 %, 9.0 % and 3.9 %, and of vaginal dryness was 12.6 %, 4.8 % and 2.4 %. No significant associations of childhood overweight/obesity or abdominal obesity with VMS or vaginal dryness were found after adjustment for childhood age, follow-up length, smoking, socioeconomic status and diet quality. Childhood overweight/obesity was associated with increased risks of more severe total (RR:1.17, 95 % CI:1.02-1.36), psychological (RR:1.19, 95 % CI:1.04-1.35) and urogenital (RR:1.29, 95 % CI:1.14-1.46) symptoms measured using the MRS. Associations with childhood abdominal obesity were mostly stronger with more severe total (RR:2.19, 95 % CI:1.48-3.23), somatic (RR:1.52, 95 % CI:1.15-2.02), psychological (RR:1.21, 95 % CI:1.04-1.42) and urogenital (RR:2.11, 95 % CI:1.39-3.20) symptoms.

Conclusions: Childhood adiposity was not associated with increased risks of more severe VMS or vaginal dryness in women aged 45-49 years. Childhood adiposity, especially abdominal obesity, was associated with more severe total, somatic, psychological and urogenital symptoms. However, the association between these symptoms and menopause is not established.
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http://dx.doi.org/10.1016/j.maturitas.2020.09.008DOI Listing
January 2021

Sesamin attenuates carrageenan-induced lung inflammation through upregulation of A20 and TAX1BP1 in rats.

Int Immunopharmacol 2020 Nov 22;88:107009. Epub 2020 Sep 22.

Department of Pharmacy, Zhejiang Hospital, Hangzhou, China. Electronic address:

Sesamin is a major component in lignans of sesame seeds, has been described to possess a lot of biological activity. The main objective of our study was to investigate the inhibitory effect and novel molecular mechanisms of sesamin on carrageenan-induced lung inflammation in rats. Here we showed that sesamin can obviously reduce polymorphonuclear neutrophils infiltration and exudate volume. Further studies exhibited sesamin can inhibit cytokines release, polymorphonuclear neutrophils markers production and the degree of lung tissues injury. Western blot analysis revealed that sesamin can inhibit the TRAF6 expression and NF-κB pathway activation in lung tissue. We found that sesamin can increase the expression of A20 and TAX1BP1 in lung tissues, and the interaction between the two molecules. In conclusion, all these results demonstrated that sesamin can attenuate carrageenan-induced lung inflammation, the mechanisms that may be related to upregulation of the novel target A20 and TAX1BP1 which can negative regulation for NF-κB pathway. Importantly, this is the first evidence showing that TAX1BP1 can be as a novel regulatory target to attenuate the lung inflammation.
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http://dx.doi.org/10.1016/j.intimp.2020.107009DOI Listing
November 2020

Expression of and Correlates with Prognosis in Patients with Breast Cancer After Radiotherapy: A Case-Control Study.

Cancer Biother Radiopharm 2020 Oct 28. Epub 2020 Oct 28.

Graduate Faculty, The First Hospital of China Medical University, Shenyang, People's Republic of China.

This study aims to explore the associations of human epidermal growth factor receptor 2 () and breast cancer susceptibility gene 1 () expression levels with prognosis and radiation sensitivity in patients with breast cancer. Breast cancer tissues, adjacent normal breast tissues, and benign breast lesions were initially obtained from 256 breast cancer patients as well as an additional 245 patients with breast lesions. Reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) was conducted to assess the expression of and in the collected tissues. Immunohistochemistry was performed to examine and -positive expression levels in the tissues. The relationship between and expression levels and radiation sensitivity as well breast cancer prognosis was assessed by the Spearman correlation analysis and Kaplan-Meier survival analysis. Compared with adjacent normal breast tissues and benign breast lesions, the breast cancer tissues exhibited high expression of mRNA and protein and low expression of mRNA and protein. Patients with positive expression had a significantly shorter survival time, and survival time of patients with positive expression was markedly longer, which were consistent with RT-qPCR results. After radiotherapy, the local failure rate of -positive patients was higher than that of the negative ones, while that of -positive patients was lower than that of the negative ones. This study suggested that breast cancer patients with high expression and low expression were less sensitive to radiotherapy with poor prognosis in breast cancer.
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http://dx.doi.org/10.1089/cbr.2020.3607DOI Listing
October 2020

A nanoplatform based on mesoporous silica-coated gold nanorods for cancer triplex therapy.

J Mater Chem B 2020 11;8(42):9686-9696

Key Laboratory of Biorheological Science and Technology of Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China.

To enhance the efficacy of nanoparticle-based cancer therapy with reduced side effects and promote its clinical translation, a biocompatible nanocomposite based on mesoporous silica-coated gold nanorods ([email protected]) for triple tumor therapy is reported in this study. The gold core served as a hyperthermia agent, while the MSN shell acted as a reservoir of chemotherapeutics owing to its excellent loading capacity. Cytochrome c with the apoptosis inducing function was anchored on the surface of [email protected] to prevent drug leakage through redox-responsive disulfide bonds. The successful construction of a nanocomposite was confirmed by characterization of the physicochemical properties. In vitro and in vivo studies demonstrated that the nanocomposite displayed an optimizing anti-tumor effect with a synergistic strategy of excellent photothermal therapy, chemotherapy and protein therapy. Therefore, this cooperative strategy paves the way for high-efficiency oncotherapy with reduced side effects.
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http://dx.doi.org/10.1039/d0tb01707hDOI Listing
November 2020

Engineering of Cascade-Responsive Nanoplatform to Inhibit Lactate Efflux for Enhanced Tumor Chemo-Immunotherapy.

ACS Nano 2020 10 25;14(10):14164-14180. Epub 2020 Sep 25.

Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing 400044, China.

As an increased product of high-rate aerobic glycolysis in tumors, lactate could regulate the immunosuppressive tumor microenvironment (TME). A PEG-CDM surface modified, GSH-dependent responsive hollow mesoporous organosilica nanoplatform loaded with hydroxycamptothecin (HCPT) and siMCT-4 was administrated for synergistic tumor chemo-immunotherapy. The nanoplatform cascaded responded to the weak acid TME and the high level of GSH in tumor cells. HCPT and siMCT-4 were continuously released from the nanoplatform for chemotherapy and inhibiting intracellular lactate efflux. The increased intracellular lactate and HCPT effectively induced tumor cell apoptosis. Moreover, the decreased extracellular lactate polarized tumor-associated macrophages (TAMs) phenotype from M2 type to M1 type and restored CD8 T cell activity . The results demonstrated that the nanoplatform effectively removed the immunosuppressive TME, inhibited tumor growth, and suppressed lung metastasis of B16F10 cells and 4T1 cells the combination of inhibiting lactate efflux and chemotherapy. Accordingly, it suggested a strategy to transform immunosuppressive tumors into "hot" tumors and inhibit the tumor growth with high efficiency .
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http://dx.doi.org/10.1021/acsnano.0c07071DOI Listing
October 2020

Rap1b but not Rap1a in the forebrain is required for learned fear.

Cell Biosci 2020 11;10:107. Epub 2020 Sep 11.

School of Life Sciences, Nanchang University, Nanchang, 330031 China.

Background: Fear is an adaptive response across species in the face of threatening cues. It can be either innate or learned through postnatal experience. We have previously shown that genetic deletion of both Rap1a and Rap1b, two isoforms of small GTPase Rap1 in forebrain, causes impairment in auditory fear conditioning. However, the specific roles of these two isoforms are not yet known.

Results: In the present study, employing mice with forebrain-restricted deletion of Rap1a or Rap1b, we found that they are both dispensable for normal acquisition of fear learning. However, Rap1b but not Rap1a knockout (KO) mice displayed impairment in the retrieval of learned fear. Subsequently, we found that the expression of c-Fos, a marker of neuronal activity, is specifically decreased in prelimbic cortex (PL) of Rap1b KO mice after auditory fear conditioning, while remained unaltered in the amygdala and infralimbic cortex (IL). On the other hand, neither Rap1a nor Rap1b knockout altered the innate fear of mice in response to their predator odor, 2,5-Dihydro-2,4,5-Trimethylthiazoline (TMT).

Conclusion: Thus, our results indicate that it is Rap1b but not Rap1a involved in the retrieval process of fear learning, and the learned but not innate fear requires Rap1 signaling in forebrain.
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http://dx.doi.org/10.1186/s13578-020-00469-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488763PMC
September 2020

A zwitterionic serine modified chitosan derivative for improving protein stability and activity.

Int J Biol Macromol 2020 Nov 15;163:1738-1746. Epub 2020 Sep 15.

Department of Materials Science and Engineering, College of Chemistry and Materials, Jinan University, Guangzhou 510632, PR China. Electronic address:

A zwitterionic phosphoryldiserine (PDS)- chitosan conjugate was synthesized via Atherton-Todd reaction, and its degree of substitution of PDS and structure were characterized by H and P NMR spectra, ICP, FTIR and XRD. Thermal analysis confirmed that there existed the freezing bound water surrounding PDS-chitosan due to the introduction of zwitterionic PDS groups onto chitosan backbone. In vitro cytotoxicity and hemolysis assay demonstrated that PDS-chitosan had excellent cell compatibility. UV adsorption and fluorescence spectra revealed that the model protein, bovine serum albumin (BSA) tended to keep its native conformation and showed better thermal stability in aqueous media in the presence of PDS-chitosan. We also found that the esterase-like activity of BSA could be enhanced by low concentration of PDS-chitosan (C = 0.33 mg/mL, C = 0.0625 and 0.125 mg/mL, pH = 7.4, T = 25 °C). The results indicated that zwitterionic PDS-chitosan showed great potential for maintaining protein function in biomedical applications.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.09.066DOI Listing
November 2020

Glial Metabolic Rewiring Promotes Axon Regeneration and Functional Recovery in the Central Nervous System.

Cell Metab 2020 11 16;32(5):767-785.e7. Epub 2020 Sep 16.

Raymond G. Perelman Center for Cellular and Molecular Therapeutics, the Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address:

Axons in the mature central nervous system (CNS) fail to regenerate after axotomy, partly due to the inhibitory environment constituted by reactive glial cells producing astrocytic scars, chondroitin sulfate proteoglycans, and myelin debris. We investigated this inhibitory milieu, showing that it is reversible and depends on glial metabolic status. We show that glia can be reprogrammed to promote morphological and functional regeneration after CNS injury in Drosophila via increased glycolysis. This enhancement is mediated by the glia derived metabolites: L-lactate and L-2-hydroxyglutarate (L-2HG). Genetically/pharmacologically increasing or reducing their bioactivity promoted or impeded CNS axon regeneration. L-lactate and L-2HG from glia acted on neuronal metabotropic GABA receptors to boost cAMP signaling. Local application of L-lactate to injured spinal cord promoted corticospinal tract axon regeneration, leading to behavioral recovery in adult mice. Our findings revealed a metabolic switch to circumvent the inhibition of glia while amplifying their beneficial effects for treating CNS injuries.
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http://dx.doi.org/10.1016/j.cmet.2020.08.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642184PMC
November 2020

Identification of Halogen-Associated Active Sites on Bismuth-Based Perovskite Quantum Dots for Efficient and Selective CO-to-CO Photoreduction.

ACS Nano 2020 Oct 23;14(10):13103-13114. Epub 2020 Sep 23.

Research Center for Environmental and Energy Catalysis, Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China, Chengdu 611731, China.

All-inorganic Pb-free bismuth (Bi) halogen perovskite quantum dots (PQDs) with distinct structural and photoelectric properties provide plenty of room for selective photoreduction of CO. However, the efficient conversion of CO-to-CO with high selectivity on Bi-based PQDs driven by solar light remains unachieved, and the precise reaction path/mechanism promoted by the surface halogen-associated active sites is still poorly understood. Herein, we screen a series of nontoxic and stable CsBiX (X = Cl, Br, I) PQDs for selective photocatalytic reduction of CO-to-CO at the gas-solid interface. Among all the reported pure-phase PQDs, the as-synthesized CsBiBr PQDs exhibited the highest CO-to-CO conversion efficiency generating 134.76 μmol g of CO yield with 98.7% selectivity under AM 1.5G simulated solar illumination. The surface halogen-associated active sites and reaction intermediates were dynamically monitored and precisely unraveled based on DRIFTS investigation. In combination with the DFT calculation, it was revealed that the surface Br sites allow for optimizing the coordination modes of surface-bound intermediate species and reducing the reaction energy of the rate-limiting step of COOH intermediate formation from CO. This work presents a mechanistic insight into the halogen-involved catalytic reaction mechanism in solar fuel production.
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http://dx.doi.org/10.1021/acsnano.0c04659DOI Listing
October 2020

Identification of Key Prognostic Biomarker and Its Correlation with Immune Infiltrates in Pancreatic Ductal Adenocarcinoma.

Dis Markers 2020 31;2020:8825997. Epub 2020 Aug 31.

Department of Graduate Faculty, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province 110001, China.

Pancreatic ductal adenocarcinoma (PDAC) is an extremely malignant tumor. The immune profile of PDAC and the immunologic milieu of its tumor microenvironment (TME) are unique; however, the mechanism of how the TME engineers the carcinogenesis of PDAC is not fully understood. This study is aimed at better understanding the relationship between the immune infiltration of the TME and gene expression and identifying potential prognostic and immunotherapeutic biomarkers for PDAC. Analysis of data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases identified differentially expressed genes (DEGs), including 159 upregulated and 53 downregulated genes. Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes enrichment were performed and showed that the DEGs were mainly enriched for the PI3K-Akt signaling pathway and extracellular matrix organization. We used the cytoHubba plugin of Cytoscape to screen out the most significant ten hub genes by four different models (Degree, MCC, DMNC, and MNC). The expression and clinical relevance of these ten hub genes were validated using Gene Expression Profiling Interactive Analysis (GEPIA) and the Human Protein Atlas, respectively. High expression of nine of the hub genes was positively correlated with poor prognosis. Finally, the relationship between these hub genes and tumor immunity was analyzed using the Tumor Immune Estimation Resource. We found that the expression of SPARC, COL6A3, and FBN1 correlated positively with infiltration levels of six immune cells in the tumors. In addition, these three genes had a strong coexpression relationship with the immune checkpoints. In conclusion, our results suggest that nine upregulated biomarkers are related to poor prognosis in PDAC and may serve as potential prognostic biomarkers for PDAC therapy. Furthermore, SPARC, COL6A3, and FBN1 play an important role in tumor-related immune infiltration and may be ideal targets for immune therapy against PDAC.
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http://dx.doi.org/10.1155/2020/8825997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7479484PMC
July 2021

Association between the Lymphotoxin- A252g Gene Polymorphism and the Risk of Sepsis and Mortality: A Meta-Analysis.

Biomed Res Int 2020 20;2020:7936434. Epub 2020 Aug 20.

The Geriatric Respiratory Department, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 611731, China.

Background: The association between the lymphotoxin- () A252G polymorphism and sepsis risk has been extensively studied, but the results have been controversial. This study is aimed at investigating the overall association between the A252G polymorphism and the risk of sepsis/septic shock and sepsis-related mortality.

Methods: We searched the PubMed and EMBASE databases to identify studies that investigated the association between the A252G polymorphism and risks of sepsis, septic shock, and mortality. The relevant data were extracted, and statistical analyses were performed using the Revman 5.0 and STATA 12 software.

Results: A total of 32 publications were included in the meta-analysis. The results demonstrated that the A252G polymorphism showed no significant association with sepsis risk (GG+GA AA: OR = 0.92, 95%CI = 0.79-1.07, = 0.27) or with sepsis shock risk (GG+GA AA: OR = 1.01, 95%CI = 0.84-1.22, = 0.91). However, in the subgroup analyzed by ethnicity, the A252G polymorphism significantly decreased sepsis risk in the Asian population for the recessive model [GG GA+AA: OR = 0.82, 95%CI = 0.68-0.99, = 0.04] but not in the Caucasian population. Moreover, comparisons between sepsis patients who survived and those who did not suggested that the A252G polymorphism decreases the risk of mortality [GG+GA vs. AA: OR = 0.57, 95%CI = 0.41-0.80, < 0.01].

Conclusion: Our results suggested that the A252G polymorphism in the gene decreased the risk of sepsis in Asians and may reduce mortality in septic individuals.
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http://dx.doi.org/10.1155/2020/7936434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7455838PMC
April 2021

Zwitterion-functionalized mesoporous silica nanoparticles for enhancing oral delivery of protein drugs by overcoming multiple gastrointestinal barriers.

J Colloid Interface Sci 2021 Jan 17;582(Pt A):364-375. Epub 2020 Aug 17.

Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address:

Oral delivery of protein or peptide drugs confronts several barriers, the intestinal epithelium and the mucus barrier on the gastrointestinal tract is deemed to be the toughest obstacles. However, overcoming these two obstacles requires contradictory surface properties of a nanocarrier. In the present work, mesoporous silica nanoparticles (MSNs) were modified with deoxycholic acid (DC) and coated with sulfobetaine 12 (SB12) for the first time to achieve both improved mucus permeation and transepithelial absorption. MSNs modified with stearic acid and coated with dilauroylphosphatidylcholine (DLPC) or Pluronic P123 were also prepared as controls. The SB12 coated DC modified MSN had high drug loading of 22.2%. The zwitterion coating endows the MSN improved mucus penetrating ability. In addition, the carrier also showed remarkable affinity with epithelial cells. The cellular uptake was significantly improved (10-fold for Caco-2 cells and 8-fold for E12 cells). The results also indicated that the DC modified carrier was able to avoid entry into lysosomes. It can increase the absorption of loaded insulin in all intestine segments and showed outstanding hypoglycemic effect in diabetic rats. The results suggest the zwitterion-functionalized MSNs might be a good candidate for oral protein delivery.
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http://dx.doi.org/10.1016/j.jcis.2020.08.010DOI Listing
January 2021

A novel missense mutation locus of cadherin 23 and the interaction of cadherin 23 and protocadherin 15 in a patient with usher syndrome.

Ophthalmic Genet 2020 10 24;41(5):501-504. Epub 2020 Aug 24.

Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin International Joint Research and Development Centre of Ophthalmology and Vision Science, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital , Tianjin, China.

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http://dx.doi.org/10.1080/13816810.2020.1768554DOI Listing
October 2020
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