Publications by authors named "Yin Xiong"

110 Publications

Role of Ki-67, MRE11, and PD-L1 as Predictive Biomarkers for Recurrence Pattern in Muscle-invasive Bladder Cancer.

Anticancer Res 2021 Aug;41(8):3851-3857

Department of Radiation Oncology, Keck School of Medicine of USC, Los Angeles, CA, U.S.A.

Background/aim: Muscle invasive bladder cancer (MIBC) is an aggressive disease with high rates of local recurrence following radical cystectomy (RC). Currently, there are no clinically validated biomarkers to predict local only recurrence (LOR) and guide adjuvant treatment decisions. This pilot study evaluated the role of Ki-67, MRE11 and PD-L1 as predictive biomarkers for recurrence patterns in patients undergoing RC for MIBC.

Patients And Methods: Our institutional cystectomy database containing cases from 1992-2014 was queried for patients with local only recurrence (LOR), and case-matched to patients with distant recurrence (DR) and no recurrence (NR). Clinicopathological data were collected and a tissue microarray was analyzed for presence of Ki-67, MRE11, and PD-L1 using immunofluorescence and immunohistochemistry.

Results: Pathologic specimens from 42 patients (18 NR, 16 LOR, and 8 DR) were reviewed. Compared to normal bladder tissue, tumors had increased expression of Ki-67 (p<0.01) and PD-L1 (p<0.05). High Ki-67 was associated with recurrence pattern (local vs. distant) on univariate analysis (p<0.05). Ki-67 cell density varied by recurrence type: LOR (1354 cells/mm), DR (557 cells/mm) and NR (1111 cells/mm) (p=0.034).

Conclusion: Our selected biomarkers could distinguish MIBC from normal bladder tissue but could not classify samples by recurrence pattern.
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http://dx.doi.org/10.21873/anticanres.15178DOI Listing
August 2021

Ophiocordyceps lanpingensis polysaccharides alleviate chronic kidney disease through MAPK/NF-κB pathway.

J Ethnopharmacol 2021 Aug 6;276:114189. Epub 2021 May 6.

Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China; Key Laboratory of Sustainable Utilization of Panax notoginseng Resources of Yunnan Province, Kunming 650500, China. Electronic address:

Ethnopharmacological Relevance: Ophiocordyceps lanpingensis (O. lanpingensis) is a traditional ethno-medicine distributed in Eastern Himalayas, which has been used by local minorities to prevent and treat urinary diseases for hundreds of years. However, the corresponding active components and related pharmacological mechanism of such medication are not clear yet.

Aims Of The Study: This study was performed to investigate the effects and potential mechanisms of O. lanpingensis polysaccharides (OLP) in the treatment of chronic kidney disease (CKD) based on our previous research results.

Materials And Methods: Methylation analysis was used to investigate the monosaccharide composition and glycosidic linkages in OLP. The animals were divided into the control group, CKD model group, losartan group and three different doses of OLP groups. The CKD mouse model was established by the adenine gavage. The histological changes of renal tissue were observed by Hematoxylin-eosin and Masson staining. Biochemical indicators, including blood urea nitrogen (BUN), serum creatinine (Scr), serum phosphorus (P), plasma calcium (Ca), reactive oxygen species (ROS), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) and malondialdehyde (MDA) were measured to evaluate the alleviation of CKD by OLP. Moreover, the expression levels of a series of cytokines related to the inflammation, apoptosis and fibrosis were analyzed to explore the possible mechanisms of OLP to treat CKD.

Results: OLP is composed of three kinds of monosaccharides. There are eight kinds of glycosidic linkages in OLP, among which →4)-Glcp-(1→ is the main linkage. OLP could significantly attenuate CKD in mice and the tubulointerstitial damage was recovered to almost normal after the treatment of OLP. Compared with the CKD model group, the levels of Scr, BUN, MDA, P in OLP treatment groups were significantly decreased; and the levels of SOD and Ca were increased after OLP treatment. Furthermore, OLP could reduce the oxidative stress of the renal tissues, decrease the expression levels of pro-inflammatory factors through TLR4-mediated MAPK and NF-κB pathway, inhibit the apoptosis of renal cells by MAPK pathway, and relieve the renal fibrosis by down-regulating the expression of TGF-β1.

Conclusions: OLP is composed of three kinds of monosaccharides and →4)-Glcp-(1→ is the main glycosidic linkage in the polysaccharide. OLP could ameliorate CKD in mice by declining the oxidative stress, inflammation, apoptosis and fibrosis in the kidneys. The study provided some evidences for the potential application of OLP in alleviating CKD.
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http://dx.doi.org/10.1016/j.jep.2021.114189DOI Listing
August 2021

A microRNA Signature Identifies Patients at Risk of Barrett Esophagus Progression to Dysplasia and Cancer.

Dig Dis Sci 2021 Mar 13. Epub 2021 Mar 13.

Department of Anatomic Pathology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Dr., Tampa, FL, 33612, USA.

Background: Progression of Barrett esophagus (BE) to esophageal adenocarcinoma occurs among a minority of BE patients. To date, BE behavior cannot be predicted on the basis of histologic features.

Aims: We compared BE samples that did not develop dysplasia or carcinoma upon follow-up of ≥ 7 years (BE nonprogressed [BEN]) with BE samples that developed carcinoma upon follow-up of 3 to 4 years (BE progressed [BEP]).

Methods: The NanoString nCounter miRNA assay was used to profile 24 biopsy samples of BE, including 13 BENs and 11 BEPs. Fifteen samples were randomly selected for miRNA prediction model training; nine were randomly selected for miRNA validation.

Results: Unpaired t tests with Welch's correction were performed on 800 measured miRNAs to identify the most differentially expressed miRNAs for cases of BEN and BEP. The top 12 miRNAs (P < .003) were selected for principal component analyses: miR-1278, miR-1301, miR-1304-5p, miR-517b-3p, miR-584-5p, miR-599, miR-103a-3p, miR-1197, miR-1256, miR-509-3-5p, miR-544b, miR-802. The 12-miRNA signature was first self-validated on the training dataset, resulting in 7 out of the 7 BEP samples being classified as BEP (100% sensitivity) and 7 out of the 8 BEN samples being classified as BEN (87.5% specificity). Upon validation, 4 out of the 4 BEP samples were classified as BEP (100% sensitivity) and 4 out of the 5 BEN samples were classified as BEN (80% specificity). Twenty-four samples were evaluated, and 22 cases were correctly classified. Overall accuracy was 91.67%.

Conclusion: Using miRNA profiling, we have identified a 12-miRNA signature able to reliably differentiate cases of BEN from BEP.
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http://dx.doi.org/10.1007/s10620-021-06863-0DOI Listing
March 2021

International policies and challenges on the legalization of traditional medicine/herbal medicines in the fight against COVID-19.

Pharmacol Res 2021 04 14;166:105472. Epub 2021 Feb 14.

Leiden University-European Center for Chinese Medicine and Natural Compounds, Institute of Biology Leiden, Leiden University, Leiden 2333BE, The Netherlands; SU Biomedicine B.V., Leiden 2333BE, The Netherlands. Electronic address:

The coronavirus disease 2019 (COVID-19) has now rapidly spread around the world, causing an outbreak of acute infectious pneumonia. To develop effective and safe therapies for the prevention and treatment of COVID-19 has become the major global public health concern. Traditional medicine (TM)/herbal medicines (HMs) have been used to treat multiple epidemics in human history, which brings hope for the fight against COVID-19 in some areas. For example, in China, India, and South Korea with traditional medication history and theory, the governments issued a series of guidelines to support TM/HMs in the medication of COVID-19. In contrast, other countries e.g. North American and European governments are typically silent on these practices, unless to warn of possible harm and overselling. Such difference is due to the discrepancy in culture, history and philosophical views of health care and medication, as well as unharmonized policies and standards in the regulation and legalization of TM/HMs among different areas. Herein, we reviewed the responses and scientific researches from seven selected countries on the policies and legalization of TM/HMs to treat COVID-19, and also analyzed the major challenges and concerns to utilize the traditional knowledge and resource.
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http://dx.doi.org/10.1016/j.phrs.2021.105472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882224PMC
April 2021

Quantification of artificial sweeteners in alcoholic drinks using direct analysis in real-time QTRAP mass spectrometry.

Food Chem 2021 Apr 8;342:128331. Epub 2020 Oct 8.

State Key Laboratory of Chemical Resource Engineering, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, College of Chemistry, Beijing University of Chemical Technology, Beijing 100029, PR China. Electronic address:

Artificial sweeteners have been widely used as replacements for sugars in foods. Rapid determination of artificial sweeteners contained in various foods are highly desirable for the routine analysis. Here, we report a robust approach based on direct analysis in real time coupled with QTRAP mass spectrometry to screen and quantitate simultaneously seven artificial sweeteners, including aspartame, saccharin, acesulfame-K, neotame, sucralose, cyclamate and alitame in alcoholic drinks. The detection method merely involved a simple sample pretreatment process, with a good linearity, low limit of quantification, satisfied recovery and relative standard deviation for each target compound. More importantly, the approach is highly sensitive and accurate in monitoring the seven artificial sweeteners in whisky, Chinese liquors, beer and wines obtained from the supermarket. The results demonstrated that the approach described here could be suitable for large-scale application in routine quality control analysis of artificial sweeteners.
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http://dx.doi.org/10.1016/j.foodchem.2020.128331DOI Listing
April 2021

MFG-E8 accelerates wound healing in diabetes by regulating "NLRP3 inflammasome-neutrophil extracellular traps" axis.

Cell Death Discov 2020 10;6:84. Epub 2020 Sep 10.

Department of Clinical Laboratory, Wuhan Fourth Hospital, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei China.

Sustained activation of NLRP3 inflammasome and release of neutrophil extracellular traps (NETs) impair wound healing of diabetic foot ulcers (DFUs). Our previous study reported that milk fat globule epidermal growth factor VIII (MFG-E8) attenuates tissue damage in systemic lupus erythematosus. However, the functional effect of MFG-E8 on "NLRP3 inflammasome-NETs" inflammatory loop in wound healing of diabetes is not completely elucidated. In this study, neutrophils from DFU patients are susceptible to undergo NETosis, releasing more NETs. The circulating levels of NET components neutrophil elastase and proteinase 3 and inflammatory cytokines IL-1β and IL-18 were significantly elevated in DFU patients compared with healthy controls or diabetic patients, in spite of higher levels of MFG-E8 in DFU patients. In diabetic mice, skin wound displayed exaggerated inflammatory response, including leukocyte infiltration, excessive activation of NLRP3 inflammasome (release of higher IL-1β, IL-18, and TNF-α), largely lodged NETs, resulting in poor angiogenesis and wound closure. When stimulated with high-dose glucose or IL-18, MFG-E8-deficient neutrophils release more NETs than WT neutrophils. After administration of recombinant MFG-E8, IL-18-primed NETosis of WT or neutrophils was significantly inhibited. Furthermore, NET and mCRAMP (component of NETs, the murine equivalent of cathelicidin LL-37 in human)-mediated activation of NLRP3 inflammasome and production of IL-1β/IL-18 were significantly elevated in macrophages compared with WT macrophages, which were also significantly dampened by the administration of rmMFG-E8. Therefore, our study demonstrated that as inhibitor of the "NLRP3 inflammasome-NETs" inflammatory loop, exogenous rMFG-E8 improves angiogenesis and accelerates wound healing, highlighting possible therapeutic potential for DFUs.
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http://dx.doi.org/10.1038/s41420-020-00318-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484765PMC
September 2020

Synergistic Bimetallic Metallic Organic Framework-Derived Pt-Co Oxygen Reduction Electrocatalysts.

ACS Nano 2020 Oct 22;14(10):13069-13080. Epub 2020 Sep 22.

Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14850, United States.

The rational design of Pt-based electrocatalysts is of paramount importance for the commercialization of proton exchange membrane fuel cells (PEMFCs). Pt-Co alloys and nitrogen-doped carbons have been shown to be effective in enhancing the kinetics of the oxygen reduction reaction (ORR). Herein, we reported on two kinds of Pt-Co electrocatalysts, PtCo ordered intermetallic and PtCo disordered alloys, supported on bimetallic MOF-derived N-doped carbon. The synergistic interaction between Pt-Co nanoparticles and Co-N-C enhanced the overall ORR activity and maintained the integrity of both structures and their electrochemical properties during long-term stability testing. The optimal activity for both PtCo and PtCo occurred after 20 000 potential cycles. The enhanced performance of PtCo was ascribed to the formation of a two-atomic-layer Pt-rich shell and the lattice strain caused by the core-shell [email protected] structure. The increased activity of PtCo was ascribed to the formation of large, spongy, and small solid nanoparticles during electrochemical dealloying and thus the exposure of more Pt sites on the surface. The strategy described herein advances our understanding of the structure-activity relationship in electrocatalysis and sheds light on the future development of more active and durable ORR electrocatalysts.
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http://dx.doi.org/10.1021/acsnano.0c04559DOI Listing
October 2020

Tumor size and focality in breast carcinoma: Analysis of concordance between radiological imaging modalities and pathological examination at a cancer center.

Ann Diagn Pathol 2020 Oct 21;48:151601. Epub 2020 Aug 21.

Department of Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. Electronic address:

Context: Accurate assessment of clinical and pathological tumor stage is crucial for patient treatment and prognosis.

Objective: The aim of this study was to assess the concordance between the tumor size and focality between radiological studies and pathology and to evaluate the impact of discrepancies on staging.

Design: Patients who underwent surgery for invasive breast carcinoma from January 1, 2014, to December 31, 2015, were identified.

Results: Three imaging modalities (mammogram, ultrasound and MRI) were compared with gross examination and final pathology. 1152 preoperative radiological studies were evaluated for focality and 1019 were evaluated for tumor size. For all 3 radiographic modalities, there was a statistically significant difference between the mean tumor size on radiology and the final pathology report (mammogram, P < .001; ultrasound, P = .004; MRI, P < .001). In 29% of radiology studies, there was a discrepancy in stage. The error rate for determining focality was 28% for mammograms, 27% for ultrasounds, and 29% for MRIs. Tumor size from gross examination correlated with microscopic tumor size in 57% of cases, but gross examination had 88% concordance with the final pathology report in determining focality.

Conclusion: Our study revealed statistically significant differences in mean tumor size reported across all 3 imaging modalities when compared to the final pathology report. MRI had the highest error rate, with a tendency to overestimate tumor size and number of foci. Among all diagnoses, cases of invasive carcinoma with an extensive intraductal component were most prone to discrepancies with imaging.
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http://dx.doi.org/10.1016/j.anndiagpath.2020.151601DOI Listing
October 2020

Total flavonoids of hawthorn leaves promote motor function recovery via inhibition of apoptosis after spinal cord injury.

Neural Regen Res 2021 Feb;16(2):350-356

School of Public Health Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China.

Flavonoids have been reported to have therapeutic potential for spinal cord injury. Hawthorn leaves have abundant content and species of total flavonoids, and studies of the effects of the total flavonoids of hawthorn leaves on spinal cord injury have not been published in or outside China. Therefore, Sprague-Dawley rats were used to establish a spinal cord injury model by Allen's method. Rats were intraperitoneally injected with 0.2 mL of different concentrations of total flavonoids of hawthorn leaves (5, 10, and 20 mg/kg) after spinal cord injury. Injections were administered once every 6 hours, three times a day, for 14 days. After treatment with various concentrations of total flavonoids of hawthorn leaves, the Basso, Beattie, and Bresnahan scores and histological staining indicated decreases in the lesion cavity and number of apoptotic cells of the injured spinal cord tissue; the morphological arrangement of the myelin sheath and nerve cells tended to be regular; and the Nissl bodies in neurons increased. The Basso, Beattie, and Bresnahan scores of treated spinal cord injury rats were increased. Western blot assays showed that the expression levels of pro-apoptotic Bax and cleaved caspase-3 were decreased, but the expression level of the anti-apoptotic Bcl-2 protein was increased. The improvement of the above physiological indicators showed a dose-dependent relationship with the concentration of total flavonoids of hawthorn leaves. The above findings confirm that total flavonoids of hawthorn leaves can reduce apoptosis and exert neuroprotective effects to promote the recovery of the motor function of rats with spinal cord injury. This study was approved by the Ethics Committee of the Guangxi Medical University of China (approval No. 201810042) in October 2018.
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http://dx.doi.org/10.4103/1673-5374.286975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896213PMC
February 2021

Hdc-expressing myeloid-derived suppressor cells promote basal-like transition and metastasis of breast cancer.

Int J Clin Exp Pathol 2020 1;13(6):1431-1443. Epub 2020 Jun 1.

Department of Pathology, The Fourth Affiliated Hospital of Nanchang University Nanchang, China.

Metastases are the greatest contributors to death from breast cancer. Here, we identified a distinct subpopulation of luminal breast cancer characterized by cytokeratin 14 (CK14) expression in secondary colonies rather than primary tumors. This entity possessed a poorer prognosis compared to their CK14 counterparts. Immunohistochemical analysis showed that myeloid-derived suppressor cells (MDSCs) were recruited into the tumor microenvironment and exhibited a close spatial relationship with CK14 cancer cells. We demonstrated that histidine decarboxylase (Hdc) is capable of labeling myeloid-biased hematopoietic stem cell/progenitor cell (HSC/HSPC) and immature myeloid cells infiltrating in tumor tissues. FACS data obtained from -CreER; eGFP; MMTV-PyVT female mice revealed an increased percentage of Hdc PMN-MDSCs in metastatic masses. Hdc PMN-MDSCs expressed high levels of canonical Wnts, including Wnt2, Wnt4, Wnt5a, and Wnt7b, to aberrantly activate Wnt/β-catenin signaling in CK14 malignant cells. β-catenin translocated from the membrane into the cytoplasm and nucleus. Targeted ablation of Hdc PMN-MDSCs-derived Wnts through and iDTR transgenic models hampered the metastatic cascade, making Hdc immature myeloid cells an attractive candidate for tailed immunotherapies.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344006PMC
June 2020

An Innovative Lithium Ion Battery System Based on a CuS Anode Material.

ACS Appl Mater Interfaces 2020 Apr 6;12(15):17396-17405. Epub 2020 Apr 6.

Department of Chemistry and Chemical Biology, Baker Laboratory, Cornell University, Ithaca, New York 14853, United States.

CuS is considered as one of the potential anode paradigms for advanced rechargeable batteries because of its high theoretical capacity (∼335 mAh·g), high and flat charge/discharge voltage plateaus (∼1.7 V vs Li/Li), stable cycling performance, and its elemental abundance. However, many studies have shown that CuS exhibits a dramatic capacity fade in carbonate-based electrolytes, which has precluded its commercialization when paired with high voltage cathodes in state-of-the-art lithium ion batteries. Here, we report on a fundamental mechanistic study of the electrochemical processes of CuS in both ether- and carbonate-based electrolytes employing synchrotron X-ray methods. Based on our findings, we developed a CuS/C composite material that suppresses its failure mechanism in carbonate-based electrolytes and further demonstrated its feasibility in lithium ion full cells for the first time. Our experiment provides the basis for the utilization of CuS in industrial-scale applications for large-scale electrical energy storage.
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http://dx.doi.org/10.1021/acsami.9b21982DOI Listing
April 2020

Steamed Attenuates Anemia in Mice With Blood Deficiency Syndrome Regulating Hematopoietic Factors and JAK-STAT Pathway.

Front Pharmacol 2019 21;10:1578. Epub 2020 Jan 21.

Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, China.

(Burk.) F. H. Chen is a medicinal herb used to treat blood disorders since ancient times, of which the steamed form exhibits the anti-anemia effect and acts with a "blood-tonifying" function according to traditional use. The present study aimed to investigate the anti-anemia effect and underlying mechanism of steamed (SPN) on mice with blood deficiency syndrome induced by chemotherapy. Blood deficiency syndrome was induced in mice by cyclophosphamide and acetylphenylhydrazine. A number of peripheral blood cells and organs (liver, kidney, and spleen) coefficients were measured. The mRNA expression of hematopoietic function-related cytokines in the bone marrow of mice was detected by RT-qPCR. The janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway was screened based on our previous analysis by network pharmacology. The expression of related proteins and cell cycle factors predicted in the pathway was determined by Western blot and RT-qPCR. SPN could significantly increase the numbers of peripheral blood cells and reverse the enlargement of spleen in a dose-dependent manner. The quantities of related hematopoietic factors in bone marrow were also increased significantly after SPN administration. SPN was involved in the cell cycle reaction and activation of immune cells through the JAK-STAT pathway, which could promote the hematopoiesis.
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http://dx.doi.org/10.3389/fphar.2019.01578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6985777PMC
January 2020

Expression of the BAD pathway is a marker of triple-negative status and poor outcome.

Sci Rep 2019 11 25;9(1):17496. Epub 2019 Nov 25.

Department of Anatomic Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA.

Triple-negative breast cancer (TNBC) has few therapeutic targets, making nonspecific chemotherapy the main treatment. Therapies enhancing cancer cell sensitivity to cytotoxic agents could significantly improve patient outcomes. A BCL2-associated agonist of cell death (BAD) pathway gene expression signature (BPGES) was derived using principal component analysis (PCA) and evaluated for associations with the TNBC phenotype and clinical outcomes. Immunohistochemistry was used to determine the relative expression levels of phospho-BAD isoforms in tumour samples. Cell survival assays evaluated the effects of BAD pathway inhibition on chemo-sensitivity. BPGES score was associated with TNBC status and overall survival (OS) in breast cancer samples of the Moffitt Total Cancer Care dataset and The Cancer Genome Atlas (TCGA). TNBC tumours were enriched for the expression of phospho-BAD isoforms. Further, the BPGES was associated with TNBC status in breast cancer cell lines of the Cancer Cell Line Encyclopedia (CCLE). Targeted inhibition of kinases known to phosphorylate BAD protein resulted in increased sensitivity to platinum agents in TNBC cell lines compared to non-TNBC cell lines. The BAD pathway is associated with triple-negative status and OS. TNBC tumours were enriched for the expression of phosphorylated BAD protein compared to non-TNBC tumours. These findings suggest that the BAD pathway it is an important determinant of TNBC clinical outcomes.
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http://dx.doi.org/10.1038/s41598-019-53695-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6877530PMC
November 2019

Cobalt-Based Nitride-Core Oxide-Shell Oxygen Reduction Electrocatalysts.

J Am Chem Soc 2019 12 25;141(49):19241-19245. Epub 2019 Nov 25.

Department of Chemistry and Chemical Biology, Baker Laboratory , Cornell University , Ithaca , New York 14853 , United States.

Developing high-performance, low-cost, and conductive nonprecious electrocatalysts for the oxygen reduction reaction (ORR) has been a key challenge for advancing fuel cell technologies. Here, we report on a novel family of cobalt nitrides (CoN/C, = 2, 3, 4) as ORR electrocatalysts in alkaline fuel cells. CoN/C exhibited the highest ORR activity among the three types of cobalt nitrides studied, with a half-wave potential () of 0.875 V vs RHE in 1 M KOH, rivaling that of commercial Pt/C (0.89 V). Moreover, CoN/C showed an 8-fold improvement in mass activity at 0.85 V, when compared to cobalt oxide, CoO/C, and a negligible degradation (Δ = 14 mV) after 10 000 potential cycles. The superior performance was ascribed to the formation of a conductive nitride core surrounded by a naturally formed thin oxide shell (about 2 nm). The conductive nitride core effectively mitigated the low conductivity of the metal oxide, and the thin oxide shell on the surface provided the active sites for the ORR. Strategies developed herein represent a promising approach for the design of other novel metal nitrides as electrocatalysts for fuel cells.
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http://dx.doi.org/10.1021/jacs.9b10809DOI Listing
December 2019

Octahedral spinel electrocatalysts for alkaline fuel cells.

Proc Natl Acad Sci U S A 2019 12 14;116(49):24425-24432. Epub 2019 Nov 14.

Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853;

Designing high-performance nonprecious electrocatalysts to replace Pt for the oxygen reduction reaction (ORR) has been a key challenge for advancing fuel cell technologies. Here, we report a systematic study of 15 different ABO/C spinel nanoparticles with well-controlled octahedral morphology. The 3 most active ORR electrocatalysts were MnCoO/C, CoMnO/C, and CoFeO/C. CoMnO/C exhibited a half-wave potential of 0.89 V in 1 M KOH, equal to the benchmark activity of Pt/C, which was ascribed to charge transfer between Co and Mn, as evidenced by X-ray absorption spectroscopy. Scanning transmission electron microscopy (STEM) provided atomic-scale, spatially resolved images, and high-energy-resolution electron-loss near-edge structure (ELNES) enabled fingerprinting the local chemical environment around the active sites. The most active MnCoO/C was shown to have a unique Co-Mn core-shell structure. ELNES spectra indicate that the Co in the core is predominantly Co while in the shell, it is mainly Co Broader Mn ELNES spectra indicate less-ordered nearest oxygen neighbors. Co in the shell occupies mainly tetrahedral sites, which are likely candidates as the active sites for the ORR. Such microscopic-level investigation probes the heterogeneous electronic structure at the single-nanoparticle level, and may provide a more rational basis for the design of electrocatalysts for alkaline fuel cells.
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http://dx.doi.org/10.1073/pnas.1906570116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6900538PMC
December 2019

Twenty-year surgical trends in a gynecologic oncology fellowship training program: Implications for practice.

Gynecol Oncol 2019 11 28;155(2):359-364. Epub 2019 Sep 28.

Department of Gynecologic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA; The University of South Florida Morsani College of Medicine, Tampa, FL, USA.

Objective: To assess whether there were any significant changes in surgical training volume over the past 20 years that might have ramifications toward preparedness for practice.

Methods: We used deidentified annual summaries of fellow case numbers for the academic years 1999 through 2018. Unpaired t-tests with Welch's correction were performed on all surgical categories for 10-year and 5-year periods.

Results: The total number of hysterectomies performed each year did not change significantly. The percent of hysterectomies performed by minimally invasive surgery increased significantly starting in 2008. There was a significant decline in the number of radical hysterectomies conducted starting after 2004, which then remained stable. There was also a significant decline in the number of bowel resections/anastomoses performed by fellows on the gynecologic oncology services that occurred and stabilized during the same time frame. There were other significant trends associated with the introduction of minimally invasive techniques.

Conclusion: The results of this study suggest the need to reevaluate fellowship training and/or the scope of surgical practice in gynecologic oncology.
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http://dx.doi.org/10.1016/j.ygyno.2019.09.013DOI Listing
November 2019

Chemical and bioactive comparison of root and rhizome in raw and steamed forms.

J Ginseng Res 2019 Jul 21;43(3):385-393. Epub 2017 Nov 21.

Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, China.

Background: The root and rhizome are historically and officially utilized medicinal parts of (PN) (Burk.) F. H. Chen, which in raw and steamed forms are used differently in practice.

Methods: To investigate the differences in chemical composition and bioactivities of PN root and rhizome between raw and steamed forms, high-performance liquid chromatography analyses and pharmacologic effects evaluated by tests of anticoagulation, antioxidation, hemostasis, antiinflammation, and hematopoiesis were combined.

Results: With the duration of steaming time, the contents of ginsenosides Rg, Re, Rb, Rd, and notoginsenoside R in PN were decreased, while those of ginsenosides Rh, 20()-Rg, 20()-Rg, Rh, and Rk were increased gradually. Raw PN samples steamed for 6 h at 120°C with stable levels of most constituents were used for the subsequent study of bioeffects. Raw PN showed better hemostasis, anticoagulation, and antiinflammation effects, while steamed PN exhibited stronger antioxidation and hematopoiesis activities. For different parts of PN, contents of saponins in PN rhizome were generally higher than those in the root, which could be related to the stronger bioactivities of rhizome compared with the same form of PN root.

Conclusion: This study provides basic information about the chemical and bioactive comparison of PN root and rhizome in both raw and steamed forms, indicating that the change of saponins may have a key role in different properties of raw and steamed PN.
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http://dx.doi.org/10.1016/j.jgr.2017.11.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6606817PMC
July 2019

A key variant in the cis-regulatory element of flowering gene Ghd8 associated with cold tolerance in rice.

Sci Rep 2019 07 3;9(1):9603. Epub 2019 Jul 3.

National Key Laboratory of Crop Genetic Improvement, College of Plant Science and Technology, Huazhong Agricultural University, Wuhan, 430070, China.

Variations in the gene promoter play critical roles in the evolution of important adaptive traits in crops, but direct links of the regulatory mutation to the adaptive change are not well understood. Here, we examine the nucleotide variations in the promoter region of a transcription factor (Ghd8) that control grain number, plant height and heading date in rice. We find that a dominant promoter type of subspecies japonica displayed a high activity for Ghd8 expression in comparison with the one in indica. Transgenic analyses revealed that higher expression levels of Ghd8 delayed heading date and enhanced cold tolerance in rice. Furthermore, a single-nucleotide polymorphism (T1279G) at the position -1279 bp that locates on the potential GA-responsive motif in the Ghd8 promoter affected the expression of this gene. The 1279 T variant has elevated expression of Ghd8, thus conferring increased cold tolerance of rice seedlings. Nucleotide diversity analysis revealed that the approximately 25-kb genomic region surrounding Ghd8 in the subspecies japonica was under significant selection pressure. Our findings demonstrate that the join effects of the regulatory and coding variants largely contribute to the divergence of japonica and indica and increase the adaptability of japonica to the cold environment.
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http://dx.doi.org/10.1038/s41598-019-45794-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6610134PMC
July 2019

Biologic Mechanisms Linked to Prognosis in Ovarian Cancer that May Be Affected by Aging.

J Cancer 2019 2;10(12):2604-2618. Epub 2019 Jun 2.

Senior Adult Oncology Program, Moffitt Cancer Center and Research Institute, Tampa FL, USA.

The increase of both life expectancy of the Western industrialized population and cancer incidence with aging is expected to result in a rapid expansion of the elderly cancer population, including patients with epithelial ovarian cancer (EOC). Although the survival of patients with EOC has generally improved over the past three decades, this progress has yet to provide benefits for elderly patients. Compared with young age, advanced age has been reported as an adverse prognostic factor influencing EOC. However, contradicting results have been obtained, and the mechanisms underlying this observation are poorly defined. Few papers have been published on the underlying biological mechanisms that might explain this prognosis trend. We provide an extensive review of mechanisms that have been linked to EOC prognosis and/or aging in the published literature and might underlie this relationship in humans.
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http://dx.doi.org/10.7150/jca.29611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6584919PMC
June 2019

Metal-Organic-Framework-Derived Co-Fe Bimetallic Oxygen Reduction Electrocatalysts for Alkaline Fuel Cells.

J Am Chem Soc 2019 Jul 27;141(27):10744-10750. Epub 2019 Jun 27.

Department of Chemistry and Chemical Biology, Baker Laboratory , Cornell University , Ithaca , New York 14853 , United States.

The oxygen reduction reaction (ORR) is considered the cornerstone for regenerative energy conversion devices involving fuel cells and electrolyzers. The development of non-precious-metal electrocatalysts is of paramount importance for their large-scale commercialization. Here, Co-Fe binary alloy embedded bimetallic organic frameworks (BMOF)s based on carbon nanocomposites have been designed with a compositionally optimized template, by a facile host-guest strategy, for ORR in alkaline media. The electrocatalyst exhibits promising electrocatalytic activity for ORR with a half-wave potential of 0.89 V in 0.1 M NaOH, comparable to state-of-the-art Pt/C electrocatalysts. More importantly, it exhibits robust durability after 30 000 potential cycles. Scanning transmission electron microscopy (STEM) and quantitative energy-dispersive X-ray (EDX) spectroscopy suggest that the Co-Fe alloy nanoparticles have a homogeneous elemental distribution of Co and Fe at the atomic-scale optimized BMOF and Co/Fe ratio of 9:1. The long-term durability is attributed to its ability to maintain its structural and compositional integrity after the cycling process, as evidenced by STEM-EDX analysis. This work provides valuable insights into the design and fabrication of novel platinum-group-metals-free highly active ORR electrocatalysts in alkaline media.
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http://dx.doi.org/10.1021/jacs.9b03561DOI Listing
July 2019

Quality Evaluation of Tubers Based on HPLC Fingerprint Analyses and Quantitative Analysis of Multi-Components by Single Marker.

Molecules 2019 Apr 17;24(8). Epub 2019 Apr 17.

Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China.

() tuber is a valuable herbal medicine used to treat many diseases. The procedure of establishing a reasonable and feasible quality assessment method for tuber is important to ensure its clinical safety and efficacy. In this research, an effective and comprehensive evaluation method for assessing the quality of has been developed, based on the analysis of high performance liquid chromatography (HPLC) fingerprint, combined with the quantitative analysis of multi-components by single marker (QAMS) method. The contents of the seven components, including gastrodin, -hydroxybenzyl alcohol, -hydroxy benzaldehyde, parishin A, parishin B, parishin C, and parishin E were determined, simultaneously, using gastrodin as the reference standard. The results demonstrated that there was no significant difference between the QAMS method and the traditional external standard method (ESM) ( > 0.05, RSD < 4.79%), suggesting that QAMS was a reliable and convenient method for the content determination of multiple components, especially when there is a shortage of reference substances. In conclusion, this strategy could be beneficial for simplifying the processes in the quality control of tuber and giving references to promote the quality standards of herbal medicines.
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http://dx.doi.org/10.3390/molecules24081521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6515102PMC
April 2019

Golden Palladium Zinc Ordered Intermetallics as Oxygen Reduction Electrocatalysts.

ACS Nano 2019 May 22;13(5):5968-5974. Epub 2019 Apr 22.

Key laboratory of Material Chemistry for Energy Conversion and Storage, Ministry of Education; Hubei Key Laboratory of Material Chemistry and Service Failure, School of Chemistry and Chemical Engineering , Huazhong University of Science and Technology , Wuhan 430074 , China.

Exploring Pt-free electrocatalysts with high activity and long durability for the oxygen reduction reaction (ORR) has been long pursued by the renewable energy materials community. In this work, we have designed an ordered intermetallic PdZn/C (O-PdZn) with a several atomic-layer Pd shell, which achieved a 3-fold enhancement in ORR mass activities (MA) in alkaline media, relative to Pd/C and Pt/C. Further Au incorporation in O-PdZn/C (Au-O-PdZn/C) yielded a catalyst with superior durability with less than 10% loss in MA after 30000 potential cycles. These effects have attributed to the rationally designed ordered structure and stabilizing effect of Au atoms. Aberration-corrected scanning transmission electron microscopy and synchrotron-based X-ray fluorescence spectroscopy were employed to show that Au not only galvanically replaced Pd and Zn on the surface but also penetrated through the PdZn lattice and distributed uniformly within the particles. Au-O-PdZn/C was also tested as an effective oxygen cathode in broad applications in rechargeable Li-air and Zn-air batteries.
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http://dx.doi.org/10.1021/acsnano.9b01961DOI Listing
May 2019

A Strategy for Increasing the Efficiency of the Oxygen Reduction Reaction in Mn-Doped Cobalt Ferrites.

J Am Chem Soc 2019 03 28;141(10):4412-4421. Epub 2019 Feb 28.

Department of Chemistry and Chemical Biology , Cornell University , Ithaca , New York 14850 , United States.

Alkaline fuel cells have drawn increasing attention as next-generation energy-conversion devices for electrical vehicles, since high pH enables the use of non-precious-metal catalysts. Herein, we report on a family of rationally designed Mn-doped cobalt ferrite (MCF) spinel nanocrystals, with an optimal composition Mn(CoFe)O (MCF-0.8), that are effective electrocatalysts for the oxygen reduction reaction. MCF-0.8 exhibits a half-wave potential ( E) of 0.89 V vs RHE in 1 M NaOH, only 0.02 V less than that of commercial Pt/C under identical testing conditions and, to the best of our knowledge, one of the highest recorded values in the literature. Moreover, MCF-0.8 exhibits remarkable durability (Δ E = 0.014 V) after 10 000 electrochemical cycles. In situ X-ray absorption spectroscopy (XAS) reveals that the superior performance of the trimetallic MCF-0.8 originates from the synergistic catalytic effect of Mn and Co, while Fe helps preserve the spinel structure during cycling. We employed in situ XAS to track the evolution of the oxidation states and the metal-oxygen distances not only under constant applied potentials (steady state) but also during dynamic cyclic voltammetry (CV) (nonsteady state). The periodic conversion between Mn(III, IV)/Co(III) and Mn(II, III)/Co(II) as well as the essentially constant oxidation state of Fe during the CV suggests collaboration efforts among Mn, Co, and Fe. Mn and Co serve as the synergistic coactive sites to catalyze the oxygen reduction, apparently resulting in the observed high activity, while Fe works to maintain the integrity of the spinel structure, likely contributing to the remarkable durability of the catalyst. These findings provide a mechanistic understanding of the electrocatalytic processes of trimetallic oxides under real-time fuel cell operating conditions. This approach provides a new strategy to design high-performance non-precious-metal electrocatalysts for alkaline fuel cells.
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http://dx.doi.org/10.1021/jacs.8b13296DOI Listing
March 2019

Long non-coding RNA ZNFX1-AS1 promotes the tumor progression and metastasis of colorectal cancer by acting as a competing endogenous RNA of miR-144 to regulate EZH2 expression.

Cell Death Dis 2019 02 15;10(3):150. Epub 2019 Feb 15.

Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Mounting evidences indicated that long non-coding RNA is dysregulated and involved in the pathology of tumors. However, the role of lncRNAs in colorectal cancer (CRC) progression is not fully determined. Differentially expressed lncRNA profile in CRC was conducted by lncRNA microarray in 15 pairs of CRC tissues and adjacent normal tissues, and validated by real-time PCR analysis in another 106 pairs of tissues. The biological effect of lncRNA ZNFX1-AS1 was evaluated by in vitro and in vivo assays. The regulation between lncRNA ZNFX1-AS1 and miR-144 was evaluated by a series of experiments. We found that lncRNA ZNFX1-AS1 expression was significantly upregulated in CRC tissues and cell lines, and the expression of lncRNA ZNFX1-AS1 was associated with aggressive tumor phenotype and poor prognosis in CRC. Functionally, knockdown of lncRNA ZNFX1-AS1 inhibited cell proliferation, invasion, in vitro and tumorigenesis and metastasis in vivo. Further investigation demonstrated that lncRNA ZNFX1-AS1 functioned as a competing endogenous RNA (ceRNA) for miR-144, thereby leading to the depression of its endogenous target gene Polycomb group protein enhancer of zeste homolog 2 (EZH2). We found that lncRNA ZNFX1-AS1 is significantly upregulated in CRC, and the newly identified lncRNA ZNFX1-AS1-miR-144-EZH2 axis is involved in the regulation of CRC progression, which might be used as potential therapeutic targets for CRC patients.
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http://dx.doi.org/10.1038/s41419-019-1332-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6377660PMC
February 2019

Unveiling Active Constituents and Potential Targets Related to the Hematinic Effect of Steamed Using Network Pharmacology Coupled With Multivariate Data Analyses.

Front Pharmacol 2018 8;9:1514. Epub 2019 Jan 8.

Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, China.

Steamed (SPN) has been used as a tonic to improve the blood deficiency syndrome (BDS) in the theory of traditional Chinese medicine. Here, we aim to unveil active constituents and potential targets related to the hematinic effect of SPN, which has not been answered before. In the study a constituent-target-disease network was constructed by combining the SPN-specific and anemia-specific target proteins with protein-protein interactions. And the network pharmacology was used to screen out the underlying targets and mechanisms of SPN treating anemia. Also, the multivariate data analyses were performed for the double screening. According to the results, 11 targets related to chemical constituents of SPN were found to be closely associated with the hematinic effect of SPN. Among them, the direct target protein of mitochondrial ferrochelatase (FECH) had the major role through the metabolic pathway. Meanwhile, Rk and 20()-Rg were predicted to be major constituents related to the hematinic effect of SPN by both multivariate data analyses and network pharmacology. And it was been validated by the pharmacologic tests that Rk and 20()-Rg could significantly increase the levels of blood routine parameters, FECH and its downstream protein of heme in mice with BDS. The study provides evidences for the mechanism understanding and drug development of SPN for the treatment of anemia.
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http://dx.doi.org/10.3389/fphar.2018.01514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331451PMC
January 2019

Revealing the atomic ordering of binary intermetallics using in situ heating techniques at multilength scales.

Proc Natl Acad Sci U S A 2019 02 22;116(6):1974-1983. Epub 2019 Jan 22.

Department of Chemistry and Chemical Biology, Baker Laboratory, Cornell University, Ithaca, NY 14853;

Ordered intermetallic nanoparticles are promising electrocatalysts with enhanced activity and durability for the oxygen-reduction reaction (ORR) in proton-exchange membrane fuel cells (PEMFCs). The ordered phase is generally identified based on the existence of superlattice ordering peaks in powder X-ray diffraction (PXRD). However, after employing a widely used postsynthesis annealing treatment, we have found that claims of "ordered" catalysts were possibly/likely mixed phases of ordered intermetallics and disordered solid solutions. Here, we employed in situ heating, synchrotron-based, X-ray diffraction to quantitatively investigate the impact of a variety of annealing conditions on the degree of ordering of large ensembles of PtCo nanoparticles. Monte Carlo simulations suggest that PtCo nanoparticles have a lower order-disorder phase transition (ODPT) temperature relative to the bulk counterpart. Furthermore, we employed microscopic-level in situ heating electron microscopy to directly visualize the morphological changes and the formation of both fully and partially ordered nanoparticles at the atomic scale. In general, a higher degree of ordering leads to more active and durable electrocatalysts. The annealed PtCo/C with an optimal degree of ordering exhibited significantly enhanced durability, relative to the disordered counterpart, in practical membrane electrode assembly (MEA) measurements. The results highlight the importance of understanding the annealing process to maximize the degree of ordering in intermetallics to optimize electrocatalytic activity.
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http://dx.doi.org/10.1073/pnas.1815643116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369780PMC
February 2019

In Situ X-ray Absorption Spectroscopy of a Synergistic Co-Mn Oxide Catalyst for the Oxygen Reduction Reaction.

J Am Chem Soc 2019 01 22;141(4):1463-1466. Epub 2019 Jan 22.

Department of Chemistry and Chemical Biology , Baker Laboratory, Cornell University , Ithaca , New York 14853 , United States.

Identifying the catalytically active site(s) in the oxygen reduction reaction (ORR), under real-time electrochemical conditions, is critical to the development of fuel cells and other technologies. We have employed in situ synchrotron-based X-ray absorption spectroscopy (XAS) to investigate the synergistic interaction of a Co-Mn oxide catalyst which exhibits impressive ORR activity in alkaline fuel cells. X-ray absorption near edge structure (XANES) was used to track the dynamic structural changes of Co and Mn under both steady state (constant applied potential) and nonsteady state (potentiodynamic cyclic voltammetry, CV). Under steady state conditions, both Mn and Co valences decreased at lower potentials, indicating the conversion from Mn(III,IV) and Co(III) to Mn(II,III) and Co(II), respectively. Rapid X-ray data acquisition, combined with a slow sweep rate in CV, enabled a 3 mV resolution in the applied potential, approaching a nonsteady (potentiodynamic) state. Changes in the Co and Mn valence states were simultaneous and exhibited periodic patterns that tracked the cyclic potential sweeps. To the best of our knowledge, this represents the first study, using in situ XAS, to resolve the synergistic catalytic mechanism of a bimetallic oxide. Strategies developed/described herein can provide a promising approach to unveil the reaction mechanism for other multimetallic electrocatalysts.
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http://dx.doi.org/10.1021/jacs.8b12243DOI Listing
January 2019

The Role and Mechanism of miRNA-1224 in the Polysaccharide Regulation of Bone Marrow-Derived Macrophages to Osteoclast Differentiation.

Rejuvenation Res 2019 Oct 15;22(5):420-430. Epub 2019 Mar 15.

Department of Nutrition and Food Hygiene, College of Public Hygiene of Guangxi Medical University, Nanning, Guangxi, China.

MicroRNAs (miRNAs) are endogenous noncoding small molecule RNAs that regulate cell proliferation, differentiation, fat metabolism, and hormone secretion. Studies have shown that miRNAs regulate the processes related to osteoporosis, including the differentiation of osteoblasts, osteoclasts, and chondrocytes, and are one of the important regulatory factors of some bone metabolic diseases. In our previous study, it has been revealed that natural compound polysaccharide (PSP) can promote osteoblast formation and block osteoclastogenesis through Wnt/β-catenin signaling pathway. This study was designed to investigate whether PSP can inhibit expression of osteoclast-related genes by Hippo signaling pathway, which was prevented by effectively blocking the expression of miR-1224. This study showed that there were 27 differentially expressed miRNAs when PSP inhibits osteoclastogenesis, the most notable of which was miR-1224. Furthermore, the study showed that PSP increased the level of Limd1, which was the target gene of miR-1224. In conclusion, these findings demonstrate that PSP suppressed osteoclastogenesis through the Hippo signaling pathway based on miR-1224. This study may aid in the development of a therapeutic approach utilizing PSP for the enhancement of bone health and prevention of osteoporosis.
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http://dx.doi.org/10.1089/rej.2018.2126DOI Listing
October 2019

Suppressing Self-Discharge with Polymeric Sulfur in Li-S Batteries.

Materials (Basel) 2018 Dec 25;12(1). Epub 2018 Dec 25.

Science and Technology on Advanced Ceramic Fibers and Composites Laboratory, College of Aerospace Science and Engineering, National University of Defense Technology, Changsha 410073, China.

Lithium⁻sulfur (Li-S) batteries, due to their high theoretical capacity, intrinsic overcharge protection, and low cost, are considered as the most promising candidates for next-generation energy storage systems. To promote widespread use of Li-S batteries, various tactics have been reported to improve the columbic efficiency and to suppress the shuttle effect. Herein, we report a novel polymeric sulfur via heat radical polymerization, for the Li-S battery. The insolubles after CS₂ washing, and the changes in XRD (X-ray diffraction) results imply the formation of polymeric sulfur. Owing to the absence of cyclic S₈ molecular, the shuttle effect is depressed, and the polymeric sulfur cathodes exhibit lower self-discharge rates, higher sulfur utilization, better rates of performance, and enhanced cycling stabilities than the commercial sublimed sulfur. Thus, polymeric sulfur provides a new train of thought and tactics for restricting the formation of the dissolution of polysulfides, and self-discharge.
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http://dx.doi.org/10.3390/ma12010064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6337404PMC
December 2018

Cigarette Smoke Extract Promotes TIM4 Expression in Murine Dendritic Cells Leading to Th2 Polarization through ERK-Dependent Pathways.

Int Arch Allergy Immunol 2019;178(3):219-228. Epub 2018 Dec 6.

Laboratory of Clinical Immunology, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, China,

Smoking is considered to be the main source of indoor pollution, and it has been identified as an important environmental factor contributing to asthma onset. We know that T helper 2 (Th2) response plays a crucial role in the process of asthma disease. We have investigated the reaction of cigarette smoke extract (CSE) on Th polarization which is controlled by dendritic cells (DCs). Stimulated by CSE, immature DCs from murine bone marrow showed upregulated levels of TIM4. Cocultured with CD4+ T cells, stimulated DCs increased the ratio of IL-4+ versus IFN-γ+ of CD4+ T cells. This suggests a differentiation towards Th2 response. Moreover, antibodies against TIM4 reversed the upexpression of the IL-4+/IFN-γ+ ratio provoked by CSE, indicating that the Th2 polarization which was induced by CSE is via TIM4 mechanisms. CSE could activate mitogen-activated protein kinase pathways like ERK and p38. Upregulation of TIM4 expression by CSE stimulation was found to be inhibited by an ERK inhibitor but not p38 and JNK. In conclusion, DC-induced Th2 polarization is a hallmark of CSE allergy, and this aspect can be explained by CSE-induced TIM4 expression.
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http://dx.doi.org/10.1159/000494505DOI Listing
May 2019