Publications by authors named "Zhiheng Wang"

115 Publications

Characterization of Vaginal Microbiota in Women With Recurrent Spontaneous Abortion That Can Be Modified by Drug Treatment.

Front Cell Infect Microbiol 2021 19;11:680643. Epub 2021 Aug 19.

Clinical Laboratory, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China.

Objective: The role of vaginal microbiota in recurrent spontaneous abortion (RSA) remains unknown. The purpose of this study was to investigate characteristics of vaginal microbiota and the effects of drug treatment on vaginal microbiota of patients with RSA.

Methods: A case-control study was performed, in which non-pregnant patients who experienced RSA were selected and divided into untreated and drug-treated groups. Drug-treated patients were subdivided into the metformin group, metformin plus aspirin group, and other drugs group. Healthy women who had live births and never experienced spontaneous abortion were enrolled in the control group. Characteristics of vaginal microbiomes of patients with RSA and healthy women and the impact of drug treatment on the microbiome was evaluated 16S rRNA gene sequencing of the V3-V4 region using the Illumina MiSeq platform.

Results: Women who underwent RSA had lower microbial richness than healthy women. Compared to controls, the relative abundance of seven taxa (, , -, and _) in the patient's vaginal microbiota changed significantly, which may be closely related to RSA. The composition of the vaginal microbial community in RSA patients was altered by drug treatment. Metformin combined with aspirin treatment significantly increased the relative abundance of vaginal spp. in patients.

Conclusion: An altered vaginal microbiome composition might be associated with RSA, which could be modified by drug treatment. The effect of metformin combined with aspirin on vaginal is worthy of attention.
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http://dx.doi.org/10.3389/fcimb.2021.680643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417370PMC
August 2021

Variance in tree growth rates provides a key link for completing the theory of forest size structure formation.

J Theor Biol 2021 11 9;529:110857. Epub 2021 Aug 9.

Institute of Ecology and Key Laboratory for Earth Surface Processes of the Ministry of Education, College of Urban and Environmental Sciences, Peking University, Beijing 100871, China. Electronic address:

In natural forests at a demographic equilibrium state, the size frequency distribution (SFD) of trees is linked with their size-dependent growth and mortality rates. While the mean growth rate (MGR) of each size class is generally used for determining the SFD, the variance in the growth rate (VGR) has always been ignored. Here, based on the analyses with Kolmogorov forward equation, we show that in general, the VGR can flatten the slope of the SFD and, in particular, can address the contradiction between the size-dependent MGR and the -2 power-law SFD in the metabolic scaling theory. We traced the origin of the VGR to the intrinsic stochasticity in the allometric growth coefficients of trees and deduced its functional form based on variance propagation. Using the forest censuses data from Barro Colorado Island, we verified the prediction of the VGR and indicated its indispensability in the theory of forest size-structure formation.
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http://dx.doi.org/10.1016/j.jtbi.2021.110857DOI Listing
November 2021

The complete chloroplast genome sequence of medicinal plant: (Zygophyllaceae).

Mitochondrial DNA B Resour 2021 19;6(8):2387-2388. Epub 2021 Jul 19.

Key Laboratory of Ecological Protection of Agro-pastoral Ecotones in the Yellow River Basin, National Ethnic Affairs Commission of the People's Republic of China, College of Biological Science & Engineering, North Minzu University, Yinchuan, PR China.

is a medicinal plant. The total chloroplast (cp) genome length of is 160,066 bp, Containing a large single copy region of 88,275 bp, two inverted repeat regions of 26,486 bp and a small single copy region of 18,855 bp. The chloroplast genome contains 132 complete genes, including 87 protein-coding genes (87 PCGs), 8 ribosomal RNA genes (8 rRNAs), and 37 tRNA genes (37 tRNAs). The overall GC content of cp DNA is 37.5%, the corresponding values of the LSC, SSC, and IR regions are 35.6%, 31.4%, and 42.8%. Phylogenetic tree shows that has the closest relationship with .
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http://dx.doi.org/10.1080/23802359.2021.1950061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8291069PMC
July 2021

Characterization of the complete chloroplast genome of (Lamiaceae).

Mitochondrial DNA B Resour 2021 2;6(8):2169-2170. Epub 2021 Jul 2.

Key Laboratory of Ecological Protection of Agro-pastoral Ecotones in the Yellow River Basin, National Ethnic Affairs Commission of the People's Republic of China, College of Biological Science & Engineering, North Minzu University, Yinchuan, Ningxia, P. R. China.

is a medicinal plant. The complete chloroplast genome sequence is 150,860 bp in length, which contains 133 complete genes, among them, 88 are protein-coding genes (88 PCGs), 8 are ribosomal RNA genes (8 rRNAs), and 37 are tRNA genes (37 tRNAs). The overall GC content of chloroplast DNA is 37.6%, the respective values of the LSC, SSC, and IR regions are 36.0%, 31.6%, and 43.0%. Phylogenetic tree shows that is a sister to and
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http://dx.doi.org/10.1080/23802359.2021.1945507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259819PMC
July 2021

Global distribution and evolutionary transitions of angiosperm sexual systems.

Ecol Lett 2021 Sep 14;24(9):1835-1847. Epub 2021 Jun 14.

Institute of Ecology and Key Laboratory for Earth Surface Processes of the Ministry of Education, College of Urban and Environmental Sciences, Peking University, Beijing, China.

Angiosperm sexual systems are fundamental to the evolution and distribution of plant diversity, yet spatiotemporal patterns in angiosperm sexual systems and their drivers remain poorly known. Using data on sexual systems and distributions of 68453 angiosperm species, we present the first global maps of sexual system frequencies and evaluate sexual system evolution during the Cenozoic. Frequencies of dioecy and monoecy increase with latitude, while hermaphrodites are more frequent in warm and arid regions. Transitions to dioecy from other states were higher than to hermaphroditism, but transitions away from dioecy increased since the Cenozoic, suggesting that dioecy is not an evolutionary end point. Transitions between hermaphroditism and dioecy increased, while transitions to monoecy decreased with paleo-temperature when paleo-temperature >0℃. Our study demonstrates the biogeography of angiosperm sexual systems from a macroecological perspective, and enhances our understanding of plant diversity patterns and their response to climate change.
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http://dx.doi.org/10.1111/ele.13815DOI Listing
September 2021

Phytogeographic history of the Tea family inferred through high-resolution phylogeny and fossils.

Syst Biol 2021 Jun 9. Epub 2021 Jun 9.

Center for Macroecology, Evolution and Climate, GLOBE Institute, University of Copenhagen, Universitetsparken 15, 2100, Copenhagen, Denmark.

The tea family (Theaceae) has a highly unusual amphi-Pacific disjunct distribution: most extant species in the family are restricted to subtropical evergreen broadleaf forests in East Asia, while a handful of species occur exclusively in the subtropical and tropical Americas. Here we used an approach that integrates the rich fossil evidence of this group with phylogenies in biogeographic analysis to study the processes behind this distribution pattern. We first combined genome-skimming sequencing with existing molecular data to build a robust species-level phylogeny for c.140 Theaceae species, resolving most important unclarified relationships. We then developed an empirical Bayesian method to incorporate distribution evidence from fossil specimens into historical biogeographic analyses and used this method to account for the spatiotemporal history of Theaceae fossils. We compared our method with an alternative Bayesian approach and show that it provides consistent results while significantly reduces computational demands which allows analyses of much larger datasets. Our analyses revealed a circumboreal distribution of the family from the early Cenozoic to the Miocene and inferred repeated expansions and retractions of the modelled distribution in the Northern Hemisphere, suggesting that the current Theaceae distribution could be the remnant of a larger continuous distribution associated with the boreotropical forest that has been hypothesized to occupy most of the northern latitudes in the early Cenozoic. These results contradict with studies that only considered current species distributions and showcase the necessity of integrating fossil and molecular data in phylogeny-based parametric biogeographic models to improve the reliability of inferred biogeographical events.
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http://dx.doi.org/10.1093/sysbio/syab042DOI Listing
June 2021

FGF21 Serum Levels in the Early Second Trimester Are Positively Correlated With the Risk of Subsequent Gestational Diabetes Mellitus: A Propensity-Matched Nested Case-Control Study.

Front Endocrinol (Lausanne) 2021 28;12:630287. Epub 2021 Apr 28.

Department of Obstetrics, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China.

Background: As an important endocrine hormone regulating glucose metabolism, fibroblast growth factor 21 (FGF21) is increased in individuals with gestational diabetes mellitus (GDM) after 24 gestational weeks. However, it is unknown whether the increase in FGF21 precedes the diagnosis of GDM.

Methods: In this nested case-control study, 133 pregnant women with GDM and 133 pregnant women with normal glucose tolerance (NGT) were identified through propensity score matching, and serum FGF21 levels were measured at 14 to 21 gestational weeks, before GDM is routinely identified. The differences in FGF21 levels were compared. The association between FGF21 and the occurrence of GDM was evaluated using logistic regression models with adjustment for confounders.

Results: The serum FGF21 levels of the GDM group at 14 to 21 gestational weeks were significantly higher than those of the NGT group overall ( < 0.001), with similar results observed between the corresponding BMI subgroups ( < 0.05). The 2nd (OR 1.224, 95% CI 0.603-2.485), 3rd (OR 2.478, 1.229-5.000), and 4th (OR 3.419, 95% CI 1.626-7.188) FGF21 quartiles were associated with greater odds of GDM occurrence than the 1st quartile after multivariable adjustments.

Conclusions: The serum FGF21 levels in GDM groups increased in the early second trimester, regardless of whether participants were stratified according to BMI. After adjusting for confounding factors, the FGF21 levels in the highest quartile were associated with more than three times higher probability of the diagnosis of GDM in the pregnancy as compared to levels in the first quartile.
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http://dx.doi.org/10.3389/fendo.2021.630287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113961PMC
April 2021

Author Correction: Vulnerabilities of protected lands in the face of climate and human footprint changes.

Nat Commun 2021 May 10;12(1):2822. Epub 2021 May 10.

Institute of Ecology and Key Laboratory for Earth Surface Processes of the Ministry of Education, College of Urban and Environmental Sciences, Peking University, Beijing, China.

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http://dx.doi.org/10.1038/s41467-021-23423-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110565PMC
May 2021

Upward shift and elevational range contractions of subtropical mountain plants in response to climate change.

Sci Total Environ 2021 Aug 5;783:146896. Epub 2021 Apr 5.

Institute of Ecology and Key Laboratory for Earth Surface Processes of the Ministry of Education, College of Urban and Environmental Sciences, Peking University, Beijing 100871, China.

Elevational range shifts of mountain species in response to climate change have profound impact on mountain biodiversity. However, current evidence indicates great controversies in the direction and magnitude of elevational range shifts across species and regions. Here, using historical and recent occurrence records of 83 plant species in a subtropical mountain, Mt. Gongga (Sichuan, China), we evaluated changes in species elevation centroids and limits (upper and lower) along elevational gradients, and explored the determinants of elevational changes. We found that 63.9% of the species shifted their elevation centroids upward, while 22.9% shifted downward. The changes in centroid elevations and range size were more strongly correlated with changes in lower than upper limits of species elevational ranges. The magnitude of centroid elevation shifts was larger than predicted by climate warming and precipitation changes. Our results show complex changes in species elevational distributions and range sizes in Mt. Gongga, and that climate change, species traits and climate adaptation of species all influenced their elevational movement. As Mt. Gongga is one of the global biodiversity hotspots, and contains many threatened plant species, these findings provide support to future conservation planning.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146896DOI Listing
August 2021

Effects of Climate, Plant Height, and Evolutionary Age on Geographical Patterns of Fruit Type.

Front Plant Sci 2021 16;12:604272. Epub 2021 Mar 16.

Institute of Ecology and Key Laboratory of Earth Surface Processes of Ministry of Education, College of Urban and Environmental Sciences, Peking University, Beijing, China.

Fruit type is a key reproductive trait associated with plant evolution and adaptation. However, large-scale geographical patterns in fruit type composition and the mechanisms driving these patterns remain to be established. Contemporary environment, plant functional traits and evolutionary age may all influence fruit type composition, while their relative importance remains unclear. Here, using data on fruit types, plant height and distributions of 28,222 (∼ 90.1%) angiosperm species in China, we analyzed the geographical patterns in the proportion of fleshy-fruited species for all angiosperms, trees, shrubs, and herbaceous species separately, and compared the relative effects of contemporary climate, ecosystem primary productivity, plant height, and evolutionary age on these patterns. We found that the proportion of fleshy-fruited species per grid cell for all species and different growth forms all showed significant latitudinal patterns, being the highest in southeastern China. Mean plant height per grid cell and actual evapotranspiration (AET) representing ecosystem primary productivity were the strongest drivers of geographical variations in the proportion of fleshy-fruited species, but their relative importance varied between growth forms. From herbaceous species to shrubs and trees, the relative effects of mean plant height decreased. Mean genus age had significant yet consistently weaker effects on proportion of fleshy-fruited species than mean plant height and AET, and environmental temperature and precipitation contributed to those of only trees and shrubs. These results suggest that biotic and environmental factors and evolutionary age of floras jointly shape the pattern in proportion of fleshy-fruited species, and improve our understanding of the mechanisms underlying geographical variations in fruit type composition. Our study also demonstrates the need of integrating multiple biotic and abiotic factors to fully understand the drivers of large-scale patterns of plant reproductive traits.
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http://dx.doi.org/10.3389/fpls.2021.604272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007967PMC
March 2021

Vulnerabilities of protected lands in the face of climate and human footprint changes.

Nat Commun 2021 03 12;12(1):1632. Epub 2021 Mar 12.

Institute of Ecology and Key Laboratory for Earth Surface Processes of the Ministry of Education, College of Urban and Environmental Sciences, Peking University, Beijing, China.

Protected areas (PAs) play a pivotal role in maintaining viable populations of species and minimizing their habitat loss. Globally, there are currently over 200,000 PAs that cover approximately 15% of land area. The post-2020 global biodiversity framework aims to expand this coverage to 30% by 2030. However, focusing only on the percentage coverage of PAs without evaluating their effectiveness may fail to achieve conservation goals. Here, we use a multidimensional approach incorporating species, climate and anthropogenic vulnerabilities to assess the threat levels in over 2500 PAs in China. We identify nearly 10% of PAs as the most threatened PAs in China and about one-fifth PAs as hotspots of climate and anthropogenic vulnerabilities. We also find high climate instability in species vulnerability hotspots, suggesting an elevated likelihood of species' extirpation therein. Our framework could be useful in assessing resiliency of global protected lands and also in selecting near optimal areas for their future expansion.
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http://dx.doi.org/10.1038/s41467-021-21914-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955075PMC
March 2021

Construction and application of a human scFv phage display library based on Cre‑LoxP recombination for anti‑PCSK9 antibody selection.

Int J Mol Med 2021 02 16;47(2):708-718. Epub 2020 Dec 16.

Jilin Collaborative Innovation Center for Antibody Engineering, Jilin Medical University, Jilin, Jilin 132013, P.R. China.

A large human natural single‑chain fragment variable (scFv) phage library was constructed based on Cre‑LoxP recombination, and used to successfully identify antibodies against proprotein convertase subtilisin/kexin type 9 (PCSK9). The library was derived from 400 blood samples, 30 bone marrow samples, and 10 cord blood samples from healthy donors. Lymphocytes were isolated from each sample and cDNA was synthesized using reverse transcription‑quantitative PCR. Two‑step overlap PCR was then used for scFv synthesis using a LoxP peptide as the linker. The scFv gene was inserted into the phagemid vector pDF by enzymatic digestion and ligation, and then transformed into Escherichia coli (E. coli) SS320 to establish a primary antibody library in the form of scFvs. A primary antibody library consisting of 5x107 peripheral blood and umbilical cord blood sources, as well as a primary antibody library of 5x107 bone marrow samples were obtained. By optimizing the recombination conditions, the primary phage library was used to infect E. coli BS1365 strain (which expresses the Cre enzyme), and a human scFv recombinant library with a size of 1x1011 was obtained through Cre‑LoxP enzyme‑mediated heavy and light chain replacement and recombination. This constructed recombinant library was employed to screen for antibodies against recombinant PCSK9. After four rounds of selection, a fully human antibody (3D2) was identified with a binding affinity of 1.96±1.56ⅹ10‑10 M towards PCSK9. In vitro, the PCSK9/low‑density lipoprotein receptor (LDLR) pathway of Hep‑G2 cells was inhibited by 3D2 treatment, thereby increasing LDL uptake in these cells. In addition, combination treatment with 3D2 and statin was more effective at increasing LDLR levels than treatment with 3D2 or statin alone. Furthermore, 3D2 resulted in a 3‑fold increase in hepatic LDLR levels, and lowered total serum cholesterol by up to 61.5% in vivo. Taken together, these results suggest that the constructed human Cre‑LoxP scFv phage display library can be used to screen fully human scFv, and that 3D2 may serve as a candidate hypolipidemic therapy.
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http://dx.doi.org/10.3892/ijmm.2020.4822DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797424PMC
February 2021

Effect of hesperidin on CORT-induced apoptosis and oxidative stress of mouse hippocampal nerve cells by up-regulating miR-146a-5p.

Pak J Pharm Sci 2020 May;33(3(Special)):1383-1388

College of Mental Health, Qiqihar Medical University, Qiqihar, China.

This study aims to investigate the effect of hesperidin on CORT-induced apoptosis and oxidative stress of mouse hippocampal nerve cells by up-regulating miR-146a-5p and related mechanism. Hesperidin was applied to CORT-induced HT-22 cells, or HT-22 cells whose expression of mir-146a-5p was up-regulated or down-regulated by CORT. The apoptosis rate was detected by flow cytometry. Expression of Cleaved-caspase-3 protein in cells was detected by Western blot. The levels of MDA, SOD and CAT in the cells were detected by enzyme-linked immunosorbent assay, and the expression of miR-146a-5p was detected by RT-qPCR. The application of hesperidin or up-regulation of miR-146a-5p can reduce the CORT-induced apoptosis rate of HT-22 cells, Cleaved caspase-3 protein expression and MAD content (p<0.05), and increase the activity of SOD and CAT and the expression of miR-146a-5p (p<0.05). In contrast, down-regulation ofmiR-146a-5p can increase the CORT-induced apoptosis rate of HT-22 cells, Cleaved caspase-3 protein expression and MAD content (p<0.05), and decrease the activity of SOD and CAT and the expression of miR-146a-5p (p<0.05). Down-regulation of miR-146a-5p expression can reverse the effects of hesperidin on CORT-induced HT-22 cell apoptosis and oxidative stress. Hesperidin may protect cells from being damaged by up-regulating miR-146a-5p to reduce CORT-induced HT-22 cell apoptosis and oxidative stress.
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May 2020

NQO1 promotes an aggressive phenotype in hepatocellular carcinoma via amplifying ERK-NRF2 signaling.

Cancer Sci 2021 Feb 13;112(2):641-654. Epub 2020 Dec 13.

The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai, China.

Patients with hepatocellular carcinoma (HCC) are usually diagnosed at the later stages and have poor survival outcomes. New molecules are urgently needed for the prognostic predication and individual treatment. Our study showed that high levels of NQO1 expression frequently exist in HCC with an obvious cancer-specific pattern. Patients with NQO1-high tumors are significantly associated with poor survival outcomes and serve as independent predictors. Functional experiments showed that NQO1 promotes the growth and aggressiveness of HCC in both in vitro and in vivo models, and the underlying mechanism involved NQO1-derived amplification of ERK/p38-NRF2 signaling. Combined block of ERK and NRF2 signaling generated stronger growth inhibition compared with any single block, especially for HCC with high-NQO1. Therefore, NQO1 is a potential biomarker for HCC early diagnosis and prognosis prediction, and also attractive for cancer-specific targets for HCC treatment.
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http://dx.doi.org/10.1111/cas.14744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894015PMC
February 2021

Spatial Patterns and Drivers of Angiosperm Sexual Systems in China Differ Between Woody and Herbaceous Species.

Front Plant Sci 2020 11;11:1222. Epub 2020 Aug 11.

Institute of Ecology and Key Laboratory for Earth Surface Processes of the Ministry of Education, College of Urban and Environmental Sciences, Peking University, Beijing, China.

Plant sexual systems play an important role in the evolution of angiosperm diversity. However, large-scale patterns in the frequencies of sexual systems (i.e. dioecy, monoecy, and hermaphroditism) and their drivers for species with different growth forms remain poorly known. Here, using a newly compiled database on the sexual systems and distributions of 19780 angiosperm species in China, we map the large-scale geographical patterns in frequencies of the sexual systems of woody and herbaceous species separately. We use these data to test the following two hypotheses: (1) the prevalence of sexual systems differs between woody and herbaceous assemblies because woody plants have taller canopies and are found in warm and humid climates; (2) the relative contributions of different drivers (specifically climate, evolutionary age, and mature plant height) to these patterns differ between woody and herbaceous species. We show that geographical patterns in proportions of different sexual systems (especially dioecy) differ between woody and herbaceous species. Geographical variations in sexual systems of woody species were influenced by climate, evolutionary age and plant height. In contrast, these have only weakly significant effects on the patterns of sexual systems of herbaceous species. We suggest that differences between species with woody and herbaceous growth forms in terms of biogeographic patterns of sexual systems, and their drivers, may reflect their differences in physiological and ecological adaptions, as well as the coevolution of sexual system with vegetative traits in response to environmental changes.
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http://dx.doi.org/10.3389/fpls.2020.01222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7432134PMC
August 2020

Progressive Multistage Learning for Discriminative Tracking.

IEEE Trans Cybern 2020 Aug 5;PP. Epub 2020 Aug 5.

Visual tracking is typically solved as a discriminative learning problem that usually requires high-quality samples for online model adaptation. It is a critical and challenging problem to evaluate the training samples collected from previous predictions and employ sample selection by their quality to train the model. To tackle the above problem, we propose a joint discriminative learning scheme with the progressive multistage optimization policy of sample selection for robust visual tracking. The proposed scheme presents a novel time-weighted and detection-guided self-paced learning strategy for easy-to-hard sample selection, which is capable of tolerating relatively large intraclass variations while maintaining interclass separability. Such a self-paced learning strategy is jointly optimized in conjunction with the discriminative tracking process, resulting in robust tracking results. Experiments on the benchmark datasets demonstrate the effectiveness of the proposed learning framework.
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http://dx.doi.org/10.1109/TCYB.2020.2985398DOI Listing
August 2020

SOX9 enhances sorafenib resistance through upregulating ABCG2 expression in hepatocellular carcinoma.

Biomed Pharmacother 2020 Sep 15;129:110315. Epub 2020 Jun 15.

The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200433, China. Electronic address:

Sorafenib is a multi-kinase blocker and one of the few suggested drug treatments for aggressive hepatocellular carcinoma (HCC) patients. However, drug resistance to sorafenib may often occur over time and cause further tumor aggression. Recently, cancer stem cells were found in HCC and were speculated to be involved in tumor progression. SOX9 is highly expressed in HCC cancer stem cells and promotes cell proliferation and self-renewal. Meanwhile, HCC patients with higher SOX9 expression show poorer prognosis. Whether SOX9 is involved in sorafenib resistance in HCC is still unclear. Here, we found that sorafenib treatment increased the proportion of SOX9 positive cells in HCC cell lines. Overexpression of exogenous SOX9 in HCC increased sorafenib resistance both in vitro and in vivo, whereas down-regulation led to inhibition of sorafenib resistance. Knock-down of SOX9 by RNA interference caused down-regulation of downstream genes, including ATP binding cassette subfamily G member 2 (ABCG2). The drug resistance to sorafenib caused by SOX9 overexpression could be ameliorated by ABCG2 inhibition in HCC cell lines. In the cohort of patients taken sorafenib, we found that patients with lower SOX9 expression had more prolonged overall survival (OS) and progression-free survival (PFS). Univariate and multivariate Cox analysis shows that SOX9 expression exerts as an independent risk factor for the OS and PFS of HCC patients with sorafenib treatment. These findings demonstrate that SOX9 enhances sorafenib resistance and may regulate this process by modulating ABCG2 expression.
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http://dx.doi.org/10.1016/j.biopha.2020.110315DOI Listing
September 2020

Body surface area, height, and body fat percentage as more sensitive risk factors of cancer and cardiovascular disease.

Cancer Med 2020 06 27;9(12):4433-4446. Epub 2020 Apr 27.

Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, P.R. China.

Background: Limited studies have compared the association between various physical measurements and the risk of cancer or cardiovascular disease (CVD). We aim to explore the best-individualized indicators of cancer and CVD risk assessment.

Methods: From May 2004 to December 2017, a community-based cohort in China involving 100 280 participants were enrolled. BMI, height, body surface area (BSA), and body fat percentage (BFP) were compared in parallel about cancer and CVD risk with the multivariable-adjusted Cox proportional hazard regression model.

Results: Within the follow-up period, 3107 (3.10%) were diagnosed with cancer and 3721 (3.71%) had CVD. Per-level increased (in tertile: T1, T2, and T3 level) BSA, height, and BFP was positively associated with the risk of overall cancer [HR (95% CI): 1.10 (1.05-1.15), 1.12 (1.07-1.18), and 1.10 (1.03-1.16), respectively], whereas BMI was insignificant. Compared with the reference group (T2), the highest BSA level (T3) was positively associated with overall cancer incidence for both male [HR (95% CI): 1.28 (1.13-1.45)] and female [HR (95% CI): 1.13 (1.00-1.28)]. The BSA, height, and BFP also significantly associated with some site-specific cancers including thyroid, stomach, breast, urinary system, and skin cancer. Meanwhile, BFP presented a strong positive association with overall CVD [HR (95% CI): 1.22 (1.15-1.30) in trend] in both gender and associated with nearly all CVD subtypes especially the myocardial infarction and heart failure.

Conclusion: BSA, height, and BFP have more sensitivity in assessing cancer risk and BFP shows the largest hazard ratios for CVD incident. We provided valuable evidence for the application of height, BSA, and BFP in routine healthcare practice. These encouraging findings should be tested in more well-defined studies for risk prediction.
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http://dx.doi.org/10.1002/cam4.3076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7300397PMC
June 2020

Leaf size of woody dicots predicts ecosystem primary productivity.

Ecol Lett 2020 Jun 6;23(6):1003-1013. Epub 2020 Apr 6.

Institute of Ecology and Key Laboratory for Earth Surface Processes of the Ministry of Education, College of Urban and Environmental Sciences, Peking University, Beijing, 100871, China.

A key challenge in ecology is to understand the relationships between organismal traits and ecosystem processes. Here, with a novel dataset of leaf length and width for 10 480 woody dicots in China and 2374 in North America, we show that the variation in community mean leaf size is highly correlated with the variation in climate and ecosystem primary productivity, independent of plant life form. These relationships likely reflect how natural selection modifies leaf size across varying climates in conjunction with how climate influences canopy total leaf area. We find that the leaf size-primary productivity functions based on the Chinese dataset can predict productivity in North America and vice-versa. In addition to advancing understanding of the relationship between a climate-driven trait and ecosystem functioning, our findings suggest that leaf size can also be a promising tool in palaeoecology for scaling from fossil leaves to palaeo-primary productivity of woody ecosystems.
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http://dx.doi.org/10.1111/ele.13503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7384143PMC
June 2020

Association of SCN1A, SCN2A, and UGT2B7 Polymorphisms with Responsiveness to Valproic Acid in the Treatment of Epilepsy.

Biomed Res Int 2020 25;2020:8096235. Epub 2020 Feb 25.

Department of Biostatistics, School of Public Health, Shandong University, Jinan, 250012 Shandong, China.

Purpose: The efficacy of valproic acid (VPA) varies widely in clinical treatment of epileptic patients. Our study is aimed at exploring a potential association between polymorphisms of SCN1A, SCN2A, and UGT2B7 genetic factors and VPA responses.

Methods: In this observational study, a total of 114 epileptic patients only treated with VPA for at least 1 year were included to explore the genetic polymorphisms of drug responses (mean follow-up time: 3.68 ± 1.78 years). Thirty-one single-nucleotide polymorphisms (SNPs) in three candidate genes that related with drug-metabolizing enzymes and receptors were genotyped.

Results: Of the 31 SNPs, eight were significantly associated with VPA responses, including rs1381105, rs2162600, rs10197716, rs2119068, rs2119067, rs353116, rs353112 and rs6740895. The interaction between rs10197716 and rs2119068 was the most significantly correlated with VPA responses compared with other combinations (the highest VPA-responsive rate 0.92 versus the lowest VPA-responsive rate 0.33, = 0.007).

Conclusion: The study indicated that eight SNPs and SNP-SNP interaction may be associated with VPA responses in Chinese Han epileptic patients. The SNPs were rs1381105 (SCN1A), rs2162600 (SCN1A), rs10197716 (SCN2A), rs2119068 (SCN2A), rs2119067 (SCN2A), rs353116 (SCN2A), rs353112 (SCN2A) and rs6740895 (SCN2A), respectively. The interaction between the three pairs of rs10197716-rs2119068, rs10197716-rs11889342 and rs7598931-rs12233719 was the most significant for VPA. This implied that these SNPs may play an important role in the pharmacogenomics mechanism of valproic acid.
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http://dx.doi.org/10.1155/2020/8096235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7063186PMC
January 2021

Preoperative diagnosis of malignant pulmonary nodules in lung cancer screening with a radiomics nomogram.

Cancer Commun (Lond) 2020 01 3;40(1):16-24. Epub 2020 Mar 3.

Department of Biostatistics, School of Public Health, Shandong University, Jinan, Shandong, 250002, P. R. China.

Background: Lung cancer is the most commonly diagnosed cancer worldwide. Its survival rate can be significantly improved by early screening. Biomarkers based on radiomics features have been found to provide important physiological information on tumors and considered as having the potential to be used in the early screening of lung cancer. In this study, we aim to establish a radiomics model and develop a tool to improve the discrimination between benign and malignant pulmonary nodules.

Methods: A retrospective study was conducted on 875 patients with benign or malignant pulmonary nodules who underwent computed tomography (CT) examinations between June 2013 and June 2018. We assigned 612 patients to a training cohort and 263 patients to a validation cohort. Radiomics features were extracted from the CT images of each patient. Least absolute shrinkage and selection operator (LASSO) was used for radiomics feature selection and radiomics score calculation. Multivariate logistic regression analysis was used to develop a classification model and radiomics nomogram. Radiomics score and clinical variables were used to distinguish benign and malignant pulmonary nodules in logistic model. The performance of the radiomics nomogram was evaluated by the area under the curve (AUC), calibration curve and Hosmer-Lemeshow test in both the training and validation cohorts.

Results: A radiomics score was built and consisted of 20 features selected by LASSO from 1288 radiomics features in the training cohort. The multivariate logistic model and radiomics nomogram were constructed using the radiomics score and patients' age. Good discrimination of benign and malignant pulmonary nodules was obtained from the training cohort (AUC, 0.836; 95% confidence interval [CI]: 0.793-0.879) and validation cohort (AUC, 0.809; 95% CI: 0.745-0.872). The Hosmer-Lemeshow test also showed good performance for the logistic regression model in the training cohort (P = 0.765) and validation cohort (P = 0.064). Good alignment with the calibration curve indicated the good performance of the nomogram.

Conclusions: The established radiomics nomogram is a noninvasive preoperative prediction tool for malignant pulmonary nodule diagnosis. Validation revealed that this nomogram exhibited excellent discrimination and calibration capacities, suggesting its clinical utility in the early screening of lung cancer.
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http://dx.doi.org/10.1002/cac2.12002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7163925PMC
January 2020

Superselective arterial embolization with drug-loaded microspheres for the treatment of unresectable breast cancer.

Gland Surg 2019 Dec;8(6):740-747

Hainan Cancer Hospital, Haikou 570000, China.

Background: To investigate the short-term efficacy and safety of drug-eluting bead transcatheter arterial chemoembolization (DEB-TACE) using CalliSpheres microspheres in the treatment of unresectable locally advanced breast cancer (LABC).

Methods: DEB-TACE using CSM was performed in 15 patients with LABC after failure of medical treatment. The efficacy was evaluated based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST). The postoperative adverse reactions and complications were analyzed. The changes of white blood cell (WBC) count, creatine kinase isoenzyme-MB (CK-MB), B-type natriuretic peptide (BNP), and carbohydrate antigen15-3 (CA15-3) before and after treatment were compared by using Wilcoxon signed-rank test.

Results: The surgeries were successful in all patients. The subjects were followed up for 2-60 months (median: 10 months). According to the mRECIST, no patient achieved complete remission (CR) 1, 3, and 5 months after surgery, and partial response (PR) was achieved in 9, 11, and 11 cases; also, there were 6, 4, and 2 stable disease (SD) cases, and 0, 0, and 2 progressive disease (PD) cases. The postoperative WBC count, CK-MB level, and BNP level were not significantly different from those before surgery, whereas the CA15-3 level significantly decreased. The main postoperative adverse reactions were pain, fever, and gastrointestinal reactions. No severe adverse reactions were observed.

Conclusions: DEB-TACE with CalliSpheres microspheres is a safe and feasible treatment for LABC. However, more multi-center studies with larger sample sizes are still warranted.
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http://dx.doi.org/10.21037/gs.2019.12.06DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6989905PMC
December 2019

Aerobic composting as an effective cow manure management strategy for reducing the dissemination of antibiotic resistance genes: An integrated meta-omics study.

J Hazard Mater 2020 03 23;386:121895. Epub 2019 Dec 23.

State Key Laboratory of Microbial Technology, Shandong University, Jinan, Shandong 250100, China. Electronic address:

Livestock manure is considered as an important source for spreading antibiotic resistance genes (ARGs) into the environment, and therefore poses a direct threat to public health. Whereas the effects of reused manure on soil microbial communities and ARGs have been studied extensively, comprehensive characterizations of microbial communities and ARGs of manure produced by different management methods are not well understood. Here, we analyzed the fate of microbial communities and ARGs of cow manure treated by three conventional management strategies: aerobic composting, mechanical drying and precipitation, applying an integrated-omics approach combining metagenomics and metaproteomics. Integrated-omics demonstrated that composted manure contained the lowest diversity of microbial community and ARGs compared with manure treated by other two strategies. Quantitative PCR methods revealed that the abundances of ARGs were reduced by over 83 % after composting for 14 days, regardless of the season. Besides, the potential ARG hosts Acinetobacter and Pseudomonas dominating mechanical drying process were sharply decreased in abundances after composting. The significant co-occurrence networks among bacteria, ARGs and transposase gene tnpA-01 in composting samples indicated the important role of these bacteria in the dissemination of ARGs. These findings offer insight into potential strategies to control the spread of ARGs during livestock manure reuse.
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http://dx.doi.org/10.1016/j.jhazmat.2019.121895DOI Listing
March 2020

Responses of four dominant dryland plant species to climate change in the Junggar Basin, northwest China.

Ecol Evol 2019 Dec 11;9(23):13596-13607. Epub 2019 Nov 11.

Institute of Ecology College of Urban and Environmental Sciences, and Key Laboratory for Earth Surface Processes of the Ministry of Education Peking University Beijing China.

Aim: Dryland ecosystems are exceedingly sensitive to climate change. Desertification induced by both climate changes and human activities seriously threatens dryland vegetation. However, the impact of climate change on distribution of dryland plant species has not been well documented. Here, we studied the potential distribution of four representative dryland plant species (, , , and ) under current and future climate scenarios in a temperate desert region, aiming to improve our understanding of the responses of dryland plant species to climate change and provide guidance for dryland conservation and afforestation.

Location: Junggar Basin, a large desert region in northwestern China.

Methods: Occurrence data of the studied species were collected from an extensive field investigation of 2,516 sampling sites in the Junggar Basin. Ensemble species distribution models using 10 algorithms were developed and used to predict the potential distribution of each studied species under current and future climate scenarios.

Result: and were likely to lose most of their current suitable habitats under future climate scenarios, while and were likely to expand their ranges or remain relatively stationary. Variable importance evaluation showed that the most important climate variables influencing species distribution differed across the studied species. These results may be explained by the different ecophysiological characteristics and adaptation strategies to the environment of the four studied species.

Main Conclusions: We explored the responses of the representative dryland plant species to climate change in the Junggar Basin in northwestern China. The different changes in suitability of different species imply that policymakers may need to reconsider the selection and combination of the afforestation species used in this area. This study can provide valuable reference for the management and conservation of dryland ecosystems under future climate change scenarios.
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http://dx.doi.org/10.1002/ece3.5817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912881PMC
December 2019

Investigation on Super-Resolution Focusing Performance of a TE-Polarized Nanoslit-Based Two-Dimensional Lens.

Nanomaterials (Basel) 2019 Dec 18;10(1). Epub 2019 Dec 18.

Shaanxi Province Key Laboratory of Thin Films Technology and Optical Test, Xi'an Technological University, Xi'an 710021, China.

Conventional optics suffer from the diffraction limit. Our recent work has predicted a nanoslit-based two-dimensional (2D) lens with transverse-electric (TE) polarized design that is capable of realizing the super-resolution focusing of light beyond the diffraction limit in the quasi-far field. Furthermore, the super-resolution capability can be kept in a high-refractive-index dielectric over a wide wavelength range from ultraviolet to visible light. Here, we systematically investigate the influence of various factors on the super-resolution focusing performance of the lens. Factors such as lens aperture, focal length and nanoslit length are considered. In particular, the influence of nanoslit length on lens focusing was ignored in the previous reports about nanoslit-based 2D lenses, since nanoslit length was assumed to be infinite. The numerical results using the finite-difference time-domain (FDTD) method demonstrate that the super-resolution focusing capability of a nanoslit-based 2D lens increases with the lens aperture and reduces with the increase of the lens focal length. On the other hand, it is notable that the length of the lens focus is not equal to but smaller than that of the nanoslits. Therefore, in order to achieve a desired focus length, a lens should be designed with longer nanoslits.
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http://dx.doi.org/10.3390/nano10010003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7023253PMC
December 2019

CPH-I and HE4 Are More Favorable Than CA125 in Differentiating Borderline Ovarian Tumors from Epithelial Ovarian Cancer at Early Stages.

Dis Markers 2019 13;2019:6241743. Epub 2019 Oct 13.

Obstetrics and Gynecology Hospital of Fudan University, China.

Aim: To evaluate the diagnosis value of serum human epididymis protein 4 (HE4), cancer antigen 125 (CA125), the Risk of Ovarian Malignancy Algorithm (ROMA), and Copenhagen Index (CPH-I) at early stages for differentiating borderline ovarian tumors from epithelial ovarian cancer.

Methods: We recruited 144 borderline ovarian tumors in FIGO stages I and II (BOT I+II), 108 epithelial ovarian cancers in FIGO stages I and II (EOC I+II), and 238 benign ovarian tumor patients with surgical treatment in the retrospective study. The concentration of HE4 and CA125 and the values of CPH-I and ROMA were assessed separately.

Results: The HE4 level and ROMA and CPH-I values of EOC I+II were all higher than that of BOT I+II and benign groups whether in all, pre-, or postmenopausal groups ( < 0.01). When distinguishing BOT I+II from EOC I+II, the AUC-ROC of CPH-I and HE4 were bigger than CA125 ( < 0.001), while the CPH-I has the highest sensitivities in all and postmenopausal groups (78.7%, 85.1%), and HE4 has the highest specificity and PPV (90.91%, 88.64%) in postmenopausal groups. Under pathological stratification, HE4, ROMA, and CPH-I of the serous EOC I+II were higher than that of BOT I+II ( < 0.001) and the AUC of the three indices were significantly bigger than CA125 ( < 0.001). However, the concentration of HE4 and CA125 and the values of CPH-I and ROMA have no significant difference between the two endometrioid subgroups. The index with the highest sensitivity and NPV among the four indices of different pathological subtype groups was CPH-I, and the index with the highest specificities and PPV was HE4.

Conclusion: CPH-I was more valuable than CA125 for differentiating BOT I+II from EOC I+II regardless of menopausal status, while HE4 might be better than CA125 for postmenopausal subgroups. HE4 and CPH-I were more favorable than CA125 for differentiating BOT I+II from EOC I+II in the case of unknown pathology or in serous type.
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http://dx.doi.org/10.1155/2019/6241743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6815620PMC
April 2020

Achieving Enhanced Thermally Activated Delayed Fluorescence Rates and Shortened Exciton Lifetimes by Constructing Intramolecular Hydrogen Bonding Channels.

ACS Appl Mater Interfaces 2019 Dec 2;11(49):45999-46007. Epub 2019 Dec 2.

State Key Laboratory of Luminescent Materials and Devices and Institute of Polymer Optoelectronic Materials and Devices , South China University of Technology , Wushan Road 381 , Guangzhou 510640 , P. R. China.

A fast radiative rate, highly suppressed nonradiation, and a short exciton lifetime are key elements for achieving efficient thermally activated delayed fluorescence (TADF) organic light-emitting diodes (OLEDs) with reduced efficiency roll-off at a high current density. Herein, four representative TADF emitters are designed and synthesized based on the combination of benzophenone (BP) or 3-benzoylpyridine (BPy3) acceptors, with dendritic 3,3″,6,6″-tetra--butyl-9'-9,3':6',9″-tercarbazole (CDTC) or 10-spiro(acridine-9,9'-thioxanthene) (TXDMAc) donors, respectively. Density functional theory simulation and X-ray diffraction analysis validated the formation of CH···N intramolecular hydrogen bonds regarding the BPy3-CDTC and BPy3-TXDMAc compounds. Notably, the construction of intramolecular hydrogen bonding within TADF emitters significantly enhances the intramolecular charge transfer (ICT) strength while reducing the donor-acceptor (D-A) dihedral angle, resulting in accelerated radiative and suppressed nonradiative processes. With short TADF exciton lifetimes (τ) and high photoluminescence quantum yields (ϕ), OLEDs employing BPy3-CDTC and BPy3-TXDMAc dopants realized maximum external quantum efficiencies (EQEs) up to 18.9 and 25.6%, respectively. Moreover, the nondoped device based on BPy3-TXDMAc exhibited a maximum EQE of 18.7%, accompanied by an extremely small efficiency loss of only 4.1% at the luminance of 1000 cd m. In particular, the operational lifetime of the sky-blue BPy3-CDTC-based device was greatly extended by 10 times in contrast to the BP-CDTC-based counterpart, verifying the idea that the in-built intramolecular hydrogen bonding strategy was promising for the realization of efficient and stable TADF-OLEDs.
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http://dx.doi.org/10.1021/acsami.9b16073DOI Listing
December 2019

Contrasting Biogeographic Patterns of Bacterial and Archaeal Diversity in the Top- and Subsoils of Temperate Grasslands.

mSystems 2019 Oct 1;4(5). Epub 2019 Oct 1.

Institute of Ecology and Key Laboratory for Earth Surface Processes of the Ministry of Education, College of Urban and Environmental Sciences, Peking University, Beijing, China

Biogeographic patterns and drivers of soil microbial diversity have been extensively studied in the past few decades. However, most research has focused on the topsoil, while the subsoil is assumed to have microbial diversity patterns similar to those of the topsoil. Here we compared patterns and drivers of microbial alpha and beta diversity in and between topsoils (0 to 10 cm) and subsoils (30 to 50 cm) of temperate grasslands in Inner Mongolia of China, covering an ∼1,500-km transect along an aridity gradient. Counter to the conventional assumption, we find contrasting biogeographic patterns of diversity and influencing factors for different bacterial and archaeal groups and between depths. While bacterial diversity remains constant or increases with increasing aridity in topsoil and decreases in subsoil, archaeal diversity decreases in topsoil and remains constant in subsoil. Microbial diversity in the topsoil is most strongly influenced by aboveground vegetation and contemporary climate but is most strongly influenced by the factor historical temperature anomaly since the Last Glacial Maximum (LGM) and by soil pH in the subsoil. Moreover, the biogeographic patterns of topsoil-subsoil community dissimilarities vary for different microbial groups and are overall most strongly influenced by soil fertility differences between depths for bacteria and by contemporary climate for archaea. These findings suggest that diversity patterns observed in the topsoil may not be readily applied to the subsoil horizons. For the subsoil in particular, historical climate plays a vital role in the spatial variation of bacterial diversity. Overall, our study provides novel information for understanding and predicting soil microbial diversity patterns at depth. Exploring the biogeographic patterns of soil microbial diversity is critical for understanding mechanisms underlying the response of soil processes to climate change. Using top- and subsoils from an ∼1,500-km temperate grassland transect, we find divergent patterns of microbial diversity and its determinants in the topsoil versus the subsoil. Furthermore, we find important and direct legacy effects of historical climate change on the microbial diversity of subsoil yet indirect effects on topsoil. Our findings challenge the conventional assumption of similar geographic patterns of soil microbial diversity along soil profiles and help to improve our understanding of how soil microbial communities may respond to future climate change in different regions with various climate histories.
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http://dx.doi.org/10.1128/mSystems.00566-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6774019PMC
October 2019

Bis-tridentate Ir Phosphors Bearing Two Fused Five-Six-Membered Metallacycles: A Strategy to Improved Photostability of Blue Emitters.

Chemistry 2019 Dec 6;25(67):15375-15386. Epub 2019 Nov 6.

Department of Chemistry and Frontier Research Center on, Fundamental and Applied Sciences of Matter, National Tsing Hua University, Hsinchu, 30013, Taiwan.

Iridium complexes bearing chelating cyclometalates are popular choices as dopant emitters in the fabrication of organic light-emitting diodes (OLEDs). In this contribution, we report a series of blue-emitting, bis-tridentate Ir complexes bearing chelates with two fused five-six-membered metallacycles, which are in sharp contrast to the traditional designs of tridentate chelates that form the alternative, fused five-five metallacycles. Five Ir complexes, Px-21-23, Cz-4, and Cz-5, have been synthesized that contain a coordinated dicarbene pincer chelate incorporating a methylene spacer and a dianionic chromophoric chelate possessing either a phenoxy or carbazolyl appendage to tune the coordination arrangement. All these tridentate chelates afford peripheral ligand-metal-ligand bite angles of 166-170°, which are larger than the typical bite angle of 153-155° observed for their five-five-coordinated tridentate counterparts, thereby leading to reduced geometrical distortion in the octahedral frameworks. Photophysical measurements and TD-DFT studies verified the inherent transition characteristics that give rise to high emission efficiency, and photodegradation experiments confirmed the improved stability in comparison with the benchmark fac-[Ir(ppy) ] in degassed toluene at room temperature. Phosphorescent OLED devices were also fabricated, among which the carbazolyl-functionalized emitter Cz-5 exhibited the best performance among all the studied bis-tridentate phosphors, showing a maximum external quantum efficiency (EQE ) of 18.7 % and CIE coordinates of (0.145, 0.218), with a slightly reduced EQE of 13.7 % at 100 cd m due to efficiency roll-off.
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http://dx.doi.org/10.1002/chem.201903707DOI Listing
December 2019

Withdrawal Notice: STK33-Dependent Transcriptional Regulation of SFTA3 Induces Cisplatin-Resistance in Lung Adenocarcinoma

Anticancer Agents Med Chem 2019 05 6. Epub 2019 May 6.

Xingtai People's Hospital of Hebei Medical University. China.

The article has been withdrawn by the Editorial office of the journal Anti-Cancer Agents in Medicinal Chemistry because of no response from the authors. Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused. The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policiesmain.php

Bentham Science Disclaimer: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.
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http://dx.doi.org/10.2174/1871520619666190507100912DOI Listing
May 2019
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