Publications by authors named "Cong Chen"

513 Publications

PLAC8 promotes adriamycin resistance via blocking autophagy in breast cancer.

J Cell Mol Med 2021 Jun 11. Epub 2021 Jun 11.

Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Adriamycin (ADM) is currently one of the most effective chemotherapeutic agents in breast cancer treatment. However, growing resistance to ADM could lead to treatment failure and poor outcome. PLAC8 was reported as a novel highly conserved protein and functioned as an oncogene or tumour suppressor in various tumours. Here, we found higher PLAC8 expression was correlated with worse outcome and aggressive phenotype in breast cancer. Breast cancer patients with higher PLAC8 expression showed potential ADM resistance. In vitro experiments further confirmed that PLAC8 inhibited by siRNA or enforced overexpression by infecting pcDNA3.1(C)-PLAC8 plasmid correspondingly decreased or increased ADM resistance. Subsequently, we demonstrated that ectopic PLAC8 expression in MCF-7/ADMR cell blocked the accumulation of the autophagy-associated protein LC3 and resulted in cellular accumulation of p62. Rapamycin-triggered autophagy significantly increased cell response to ADM, while the autophagy inhibitor 3-MA enhanced ADM resistance. 3-MA and PLAC8 could synergistically cause ADM resistance via blocking the autophagy process. Additionally, the down-regulation of p62 by siRNA attenuated the activation of autophagy and PLAC8 expression in breast cancer cells. Thus, our findings suggest that PLAC8, through the participation of p62, inhibits autophagy and consequently results in ADM resistance in breast cancer. PLAC8/p62 pathway may act as novel therapeutic targets in breast cancer treatment and has potential clinical application in overcoming ADM resistance.
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http://dx.doi.org/10.1111/jcmm.16706DOI Listing
June 2021

High Expression of RhoBTB3 Predicts Favorable Chemothrapy Outcomes in non-M3 Acute Myeloid Leukemia.

J Cancer 2021 17;12(14):4229-4239. Epub 2021 May 17.

Department of Hematology, XiangYa Hospital, Central South University, XiangYa Road No.87, Changsha 410008, China.

The expression patterns and prognostic significance of the Rho family GTPases in acute myeloid leukemia have not been systematically studied yet. In our study, we analyzed the expression patterns of 21 Rho family GTPases gene members in AML patients based on GEPIA database. 10 gene members with significant differential expression in AML tissue and healthy tissue were selected for subsequent research. Survival curve analysis in TCGA and GEO dataset preliminary showed that RhoBTB3 is related with the prognosis of non-M3 AML patients. The differential expression of RhoBTB3 on AML bone marrow and normal bone marrow was verified by RT-qPCR. We performed Kaplan-Meier survival analysis and Multivariate Cox analysis to assess the prognostic value of RhoBTB3 in non-M3 AML patients with different treatment regimens. Gene functional enrichment analysis of RhoBTB3 was performed using GO, KEGG and PPI network. The AML patients from TCGA database were partitioned into 2 groups based on different treatment regimens: chemotherapy group and allo-HSCT group. In chemotherapy group, patients with higher expression level of RhoBTB3 showed relatively longer OS and EFS, multivariate Cox analysis revealed high RhoBTB3 mRNA expression as an independent favorable prognostic factor. However, in allo-HSCT group, no significant difference of OS and EFS were found between RhoBTB3 high and low subgroups. Meanwhile, allo-HSCT could circumvent the unfavorable prognosis that was associated with downregulation of RhoBTB3. Functional enrichment analysis showed the association of RhoBTB3 expression with several fundamental physiological components and pathways, including extracellular matrix components, extracellular structure organization, and cytokine-cytokine receptor interaction. Our study identified RhoBTB3 as a prognostic marker and may aid in the selection of the appropriate treatment options between chemotherapy and allo-HCST in non-M3 AML patients. Further researches are necessary to clarify the involvement of RhoBTB3 in the pathogenesis of AML.
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http://dx.doi.org/10.7150/jca.50472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176412PMC
May 2021

Co-expression Network Revealed Roles of RNA mA Methylation in Human β-Cell of Type 2 Diabetes Mellitus.

Front Cell Dev Biol 2021 18;9:651142. Epub 2021 May 18.

The Institute of Rehabilitation Industry, Fujian University of Traditional Chinese Medicine, Fuzhou, China.

RNA mA methylation plays an important role in the pathogenesis of type 2 diabetes mellitus (T2DM). RNA modifications and RNA-modifying regulators have recently emerged as critical factors involved in β-cell function and insulin resistance, including "writers," "erasers," and "readers." However, their key roles in regulating gene expression in T2DM remain unclear. The construction of co-expression network could provide a cue to resolve this complex regulatory pathway. We collected the transcriptome datasets of β-cell in diabetic patients, calculated the partial correlation coefficient, excluded the influence from control variables of diabetes related genes, and identified the genes significantly co-expressed with mA regulators. A total of 985 genes co-expressed with mA regulators (Co-mAR) were identified, which were enriched in metabolic process, MAPK and EGFR signaling pathways. Some of them have been confirmed to play a pivotal role in T2DM, including , , , , and , etc. Further, we analyzed the mA modification characteristics of Co-mAR in β-cell and identified 228 Co-mAR containing mA methylation sites, involving in several key signaling pathways regulating T2DM. We finally screened out 13 eQTL-SNPs localized in Co-mARs, and 4 have been reported strongly associated with diabetes, including , , , and . This co-expression analysis provides important information to reveal the potential regulatory mechanism of RNA mA methylation in T2DM.
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http://dx.doi.org/10.3389/fcell.2021.651142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168466PMC
May 2021

Study on the Inhibitory Effects of Naringenin-Loaded Nanostructured Lipid Carriers Against Nonalcoholic Fatty Liver Disease.

J Biomed Nanotechnol 2021 May;17(5):942-951

Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, Peking University, Beijing 100191, China.

Naringenin (NGN) can be used to inhibit the progression of nonalcoholic fatty liver disease (NAFLD) in mice, but its poor water solubility limits its applications. Nanostructured lipid carriers (NLCs) have recently attracted much attention in the field of nanodrug delivery systems because they increase the drug loading capacity and impressively enhance the solubility of indissolvable drugs. Herein, a thin-film dispersion method was used to prepare naringenin-loaded nanostructured lipid carriers (NGN-NLCs). These NGN-NLCs have a narrow size distribution of 171.9 ±2.0 nm, a high drug loading capacity of 23.7 ± 0.3%, a high encapsulation efficiency of 99.9 ± 0.0% and a drug release rate of 86.2 ± 0.4%. NGN- NLCs elevated the pharmacokinetic parameters (C and AUC) of NGN, accelerated NGN transepithelial transport in MDCK cells and intestinal absorption in the jejunum and ileum, and reduced hepatic lipid accumulation in an oleic acid (OA) plus lipopolysaccharide (LPS)-induced lipid deposition cell model in primary hepatocytes and in a methionine/choline deficient (MCD) diet-induced NAFLD mouse model. A detailed study of the mechanism showed that this NLC formulation elevated the drug release rate in simulated intestinal solutions the transepithelial transport in MDCK cells, the oral absorption in mice and the intestinal absorption of NGN. Thus, NGN-NLCs significantly enhanced the inhibitory effects of NGN on MCD diet induced mouse NAFLD.
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http://dx.doi.org/10.1166/jbn.2021.3077DOI Listing
May 2021

Designing Zn-doped nickel sulfide catalysts with an optimized electronic structure for enhanced hydrogen evolution reaction.

Nanoscale 2021 Jun 1;13(22):10127-10132. Epub 2021 Jun 1.

School of Materials Science and Engineering, Hebei University of Technology, Dingzigu Road 1, Tianjin 300130, P. R. China.

Designing non-noble-metal electrocatalysts with excellent performance and economic benefits toward the hydrogen evolution reaction (HER) is extremely crucial for future energy development. In particular, the rational cationic-doped strategy can effectively tailor the electronic structure of the catalysts and improve the free energy of the adsorbed intermediate, thus enhancing HER performance. Herein we reported Zn-doped NiS nanosheet arrays supported on Ni foam (Zn-NiS/NF) that were synthesized by a two-step hydrothermal process for improving HER catalysis under alkaline conditions. Remarkably, the obtained Zn-NiS/NF displays excellent HER catalytic performance with an overpotential of 78 mV to reach a current density of 10 mA cm and dramatic long-term stability for 18 h in 1 M KOH. In addition, the results based on the density functional theory calculations reveal that Zn dopants can modulate the electronic structure of NiS and optimize the hydrogen adsorption free energy (ΔG). Thus cationic-doping engineering provides an efficient method to enhance the intrinsic activities of transition-metal sulfides, which may contribute to the development of nonprecious electrocatalysts for HER.
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http://dx.doi.org/10.1039/d1nr01726hDOI Listing
June 2021

Clinical characteristics of low-grade tumor-related epilepsy and its predictors for surgical outcome.

Ann Clin Transl Neurol 2021 May 31. Epub 2021 May 31.

Epilepsy Center, Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Objectives: Low-grade tumors are the most common neoplasms inducing focal epilepsy; however, the short- and medium-term efficacy of surgery in epilepsy patients with low-grade tumors remains underappreciated. This study aims to summarize the clinical characteristics of epilepsy patients with low-grade tumors and to identify factors associated with postsurgical seizure-free outcomes.

Methods: We retrospectively reviewed consecutive patients with low-grade tumors who underwent subsequent epilepsy surgery in our epilepsy center, between 2012 and 2018 with a minimum follow-up of 1 year. Using Engel's classification and Kaplan-Meier survival analysis, we assessed postoperative seizure freedom over time. Demographical, electroclinical, and other presurgical evaluations were then evaluated for association with postoperative seizure outcome.

Results: The cohort included a total of 132 patients: 79 males and 53 females. Among them, 110 (83.33%) were seizure-free through their last follow-up. The Engel class I outcomes were 90.15%, 87.76%, 85.53%, 82.46%, and 73.17% at the end of the 1st, 2nd, 3rd, 4th, and 5th postoperative years, respectively. Multivariate logistic analysis revealed that longer epilepsy duration (p < 0.001, OR 1.091, 95% CI 1.040-1.144) and incomplete resection (p = 0.009, OR 3.673, 95% CI 1.393-9.684) were independently associated with seizure recurrence through the last follow-up.

Conclusions: Surgical treatment for seizure control in patients with low-grade tumors provides excellent short- and median-term outcomes.
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http://dx.doi.org/10.1002/acn3.51387DOI Listing
May 2021

Comparison of Duration of Response vs Conventional Response Rates and Progression-Free Survival as Efficacy End Points in Simulated Immuno-oncology Clinical Trials.

JAMA Netw Open 2021 May 3;4(5):e218175. Epub 2021 May 3.

Merck & Co Inc, Kenilworth, New Jersey.

Importance: Phase 2 trials and early efficacy end points play a crucial role in informing decisions about whether to continue to phase 3 trials. Conventional end points, such as objective response rate (ORR) and progression-free survival (PFS), have demonstrated inconsistent associations with overall survival (OS) benefits in immune checkpoint inhibitor (ICI) trials. Restricted mean duration of response (DOR) is a rigorous metric that combines both response status and duration information. However, its utility in clinical development has not been comprehensively explored.

Objective: To determine whether using restricted mean DOR in phase 2 trials can advance promising regimens to phase 3 trials sooner and eliminate unfavorable regimens earlier and with a higher degree of confidence compared with PFS and ORR.

Design, Setting, And Participants: This simulated modeling study randomized phase 2 screening trials by resampling 1376 patients from 2 completed randomized phase 3 trials of ICIs. Data were analyzed from August 2019 to July 2020.

Exposures: Use of ICIs.

Main Outcomes And Measures: Restricted mean DOR, PFS, ORR, and OS were estimated and compared between groups. Three scenarios were considered: (1) significant differences in OS, PFS, and ORR; (2) significant differences in OS and noticeable differences in ORR but not PFS; and (3) no differences in OS, PFS, or ORR. For each setting, 5000 randomized phase 2 trials with different sample sizes were simulated, with additional censoring applied to mimic staggered accruals and ensure fair comparisons between different analysis methods. Probabilities of concluding positive phase 2 trials using PFS, ORR, and DOR were summarized and compared.

Results: The restricted mean DOR difference correctly estimated a positive OS benefit more frequently than did the ORR or PFS tests, across different sample sizes, significance levels, and censoring levels evaluated. When both OS and PFS differed, the ranges of true-positive or power rates were 79.2% to 98.7% for DOR, 56.3% to 93.2% for PFS, and 67.0% to 96.0% for ORR. When OS differed but PFS did not, the ranges of power rates were 24.0% to 76.0% for DOR, 3.0% to 19.0% for PFS, and 10.5% to 38.0% for ORR. When OS was similar, the false-positive rate of restricted mean DOR test was close to the chosen significance level.

Conclusions And Relevance: These findings suggest that restricted mean DOR in randomized phase 2 trials is potentially more sensitive and useful than PFS and ORR in estimating the subsequent phase 3 conclusions and, thus, may be considered to complementarily facilitate decision-making in future clinical development.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.8175DOI Listing
May 2021

Switching Spinless and Spinful Topological Phases with Projective PT Symmetry.

Phys Rev Lett 2021 May;126(19):196402

Research Laboratory for Quantum Materials, Singapore University of Technology and Design, Singapore 487372, Singapore.

A fundamental dichotomous classification for all physical systems is according to whether they are spinless or spinful. This is especially crucial for the study of symmetry-protected topological phases, as the two classes have distinct symmetry algebra. As a prominent example, the spacetime inversion symmetry PT satisfies (PT)^{2}=±1 for spinless/spinful systems, and each class features unique topological phases. Here, we reveal a possibility to switch the two fundamental classes via Z_{2} projective representations. For PT symmetry, this occurs when P inverses the gauge transformation needed to recover the original Z_{2} gauge connections under P. As a result, we can achieve topological phases originally unique for spinful systems in a spinless system, and vice versa. We explicitly demonstrate the claimed mechanism with several concrete models, such as Kramers degenerate bands and Kramers Majorana boundary modes in spinless systems, and real topological phases in spinful systems. Possible experimental realization of these models is discussed. Our work breaks a fundamental limitation on topological phases and opens an unprecedented possibility to realize intriguing topological phases in previously impossible systems.
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http://dx.doi.org/10.1103/PhysRevLett.126.196402DOI Listing
May 2021

Polyphyllin Ⅲ-Induced Ferroptosis in MDA-MB-231 Triple-Negative Breast Cancer Cells can Be Protected Against by KLF4-Mediated Upregulation of xCT.

Front Pharmacol 2021 10;12:670224. Epub 2021 May 10.

Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Ferroptosis, which is characterized by the accumulation of intracellular iron and subsequent lipid peroxidation, is a newly discovered form of regulated cell death and plays an important role in tumor suppression. Herein, we showed that Polyphyllin III, which is a major saponin extracted from rhizomes, exerted its proliferation-inhibitory effect on MDA-MB-231 triple-negative breast cancer cells mainly through ACSL4-mediated lipid peroxidation elevation and ferroptosis induction. ACSL4 deletion partly attenuated Polyphyllin III-induced ferroptosis. Polyphyllin III treatment also induced KLF4-mediated protective upregulation of xCT, which is the negative regulator of ferroptosis. Interestingly, combination with the xCT inhibitor sulfasalazine (SAS) or downregulation of KLF4 sensitized MDA-MB-231 cells to Polyphyllin III. Furthermore, xenograft models, SAS significantly sensitized MDA-MB-231 breast cancer cells to Polyphyllin III, likely by enhancing intracellular lipid peroxidation and ferroptosis. The results of this study collectively demonstrated that Polyphyllin III exerts its anticancer effect by inducing ferroptosis via ACSL4 in MDA-MB-231 breast cancer cells. More importantly, we observed for the first time that KLF4-mediated xCT upregulation serves as negative feedback during ferroptosis progression, which might contribute to drug resistance in cancer treatment.
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http://dx.doi.org/10.3389/fphar.2021.670224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141818PMC
May 2021

Independent action models and prediction of combination treatment effects for response rate, duration of response and tumor size change in oncology drug development.

Contemp Clin Trials 2021 May 15;106:106434. Epub 2021 May 15.

Oncology Early Development, Merck & Co., Inc., Kenilworth, NJ 07033, USA.

An unprecedented number of new cancer targets are in development, and most are being developed in combination therapies. Early oncology development is strategically challenged in choosing the best combinations to move forward to late stage development. The most common early endpoints to be assessed in such decision-making include objective response rate, duration of response and tumor size change. In this paper, using independent-drug-action and Bliss-drug-independence concepts as a foundation, we introduce simple models to predict combination therapy efficacy for duration of response and tumor size change. These models complement previous publications using the independent action models (Palmer 2017, Schmidt 2020) to predict progression-free survival and objective response rate and serve as new predictive models to understand drug combinations for early endpoints. The models can be applied to predict the combination treatment effect for early endpoints given monotherapy data, or to estimate the possible effect of one monotherapy in the combination if data are available from the combination therapy and the other monotherapy. Such quantitative work facilitates strategic planning and decision making in early stage oncology drug development.
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http://dx.doi.org/10.1016/j.cct.2021.106434DOI Listing
May 2021

Splicing factor SRSF1 promotes breast cancer progression via oncogenic splice switching of PTPMT1.

J Exp Clin Cancer Res 2021 May 15;40(1):171. Epub 2021 May 15.

Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.

Background: Intensive evidence has highlighted the effect of aberrant alternative splicing (AS) events on cancer progression when triggered by dysregulation of the SR protein family. Nonetheless, the underlying mechanism in breast cancer (BRCA) remains elusive. Here we sought to explore the molecular function of SRSF1 and identify the key AS events regulated by SRSF1 in BRCA.

Methods: We conducted a comprehensive analysis of the expression and clinical correlation of SRSF1 in BRCA based on the TCGA dataset, Metabric database and clinical tissue samples. Functional analysis of SRSF1 in BRCA was conducted in vitro and in vivo. SRSF1-mediated AS events and their binding motifs were identified by RNA-seq, RNA immunoprecipitation-PCR (RIP-PCR) and in vivo crosslinking followed by immunoprecipitation (CLIP), which was further validated by the minigene reporter assay. PTPMT1 exon 3 (E3) AS was identified to partially mediate the oncogenic role of SRSF1 by the P-AKT/C-MYC axis. Finally, the expression and clinical significance of these AS events were validated in clinical samples and using the TCGA database.

Results: SRSF1 expression was consistently upregulated in BRCA samples, positively associated with tumor grade and the Ki-67 index, and correlated with poor prognosis in a hormone receptor-positive (HR+) cohort, which facilitated proliferation, cell migration and inhibited apoptosis in vitro and in vivo. We identified SRSF1-mediated AS events and discovered the SRSF1 binding motif in the regulation of splice switching of PTPMT1. Furthermore, PTPMT1 splice switching was regulated by SRSF1 by binding directly to its motif in E3 which partially mediated the oncogenic role of SRSF1 by the AKT/C-MYC axis. Additionally, PTPMT1 splice switching was validated in tissue samples of BRCA patients and using the TCGA database. The high-risk group, identified by AS of PTPMT1 and expression of SRSF1, possessed poorer prognosis in the stage I/II TCGA BRCA cohort.

Conclusions: SRSF1 exerts oncogenic roles in BRCA partially by regulating the AS of PTPMT1, which could be a therapeutic target candidate in BRCA and a prognostic factor in HR+ BRCA patient.
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http://dx.doi.org/10.1186/s13046-021-01978-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8122567PMC
May 2021

Photon management to reduce energy loss in perovskite solar cells.

Chem Soc Rev 2021 May 12. Epub 2021 May 12.

State Key Laboratory of Integrated Optoelectronics, College of Electronic Science and Engineering, Jilin University, 2699 Qianjin Street, Changchun, 130012, People's Republic of China.

Despite the rapid development of perovskite solar cells (PSCs) over the past few years, the conversion of solar energy into electricity is not efficient enough or cost-competitive yet. The principal energy loss in the conversion of solar energy to electricity fundamentally originates from the non-absorption of low-energy photons ascribed to Shockley-Queisser limits and thermalization losses of high-energy photons. Enhancing the light-harvesting efficiency of the perovskite photoactive layer by developing efficient photo management strategies with functional materials and arrays remains a long-standing challenge. Here, we briefly review the historical research trials and future research trends to overcome the fundamental loss mechanisms in PSCs, including upconversion, downconversion, scattering, tandem/graded structures, texturing, anti-reflection, and luminescent solar concentrators. We will deeply emphasize the availability and analyze the importance of a fine device structure, fluorescence efficiency, material proportion, and integration position for performance improvement. The unique energy level structure arising from the 4fn inner shell configuration of the trivalent rare-earth ions gives multifarious options for efficient light-harvesting by upconversion and downconversion. Tandem or graded PSCs by combining a series of subcells with varying bandgaps seek to rectify the spectral mismatch. Plasmonic nanostructures function as a secondary light source to augment the light-trapping within the perovskite layer and carrier transporting layer, enabling enhanced carrier generation. Texturing the interior using controllable micro/nanoarrays can realize light-matter interactions. Anti-reflective coatings on the top glass cover of the PSCs bring about better transmission and glare reduction. Photon concentration through perovskite-based luminescent solar concentrators offers a path to increase efficiency at reduced cost and plays a role in building-integrated photovoltaics. Distinct from other published reviews, we here systematically and hierarchically present all of the photon management strategies in PSCs by presenting the theoretical possibilities and summarizing the experimental results, expecting to inspire future research in the field of photovoltaics, phototransistors, photoelectrochemical sensors, photocatalysis, and especially light-emitting diodes. We further assess the overall possibilities of the strategies based on ultimate efficiency prospects, material requirements, and developmental outlook.
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http://dx.doi.org/10.1039/d0cs01488eDOI Listing
May 2021

Chronic myeloid leukemia with a significant increase of monocytes and rare karyotype: A case report and literature review.

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2021 Mar;46(3):322-327

Department of Gastroenterology, Changsha Central Hospital, Changsha 410004, China.

Chronic myeloid leukemia with a significant increase of monocytes is rare and difficult to identify from chronic myelo-monocytic leukemia in clinic. A 31-year-old male patient with systemic pain was initially diagnosed as chronic myelo-monocytic leukemia, who was finally diagnosed as chronic myeloid leukemia by fusion gene and chromosome examination. In addition to the typical Ph chromosome, a rare chromosome translocation t(2; 7)(p13; p22) was observed. The detection of monocyte subsets by multi-parameter flow cytometry is a diagnostic marker to distinguish the above 2 diseases. The relationship between fusion genes and mononucleosis is not clear. Tyrosine kinase inhibitors or allogeneic hematopoietic stem cell transplantation can be used in the treatment for this disease.
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http://dx.doi.org/10.11817/j.issn.1672-7347.2021.200273DOI Listing
March 2021

Simultaneous Conduction and Valence Band Regulation of Indium-Based Quantum Dots for Efficient H Photogeneration.

Nanomaterials (Basel) 2021 Apr 26;11(5). Epub 2021 Apr 26.

Shandong Provincial Key Laboratory of Molecular Engineering, School of Chemistry and Chemical Engineering, Qilu University of Technology (Shandong Academy of Science), Jinan 250353, China.

Indium-based chalcogenide semiconductors have been served as the promising candidates for solar H evolution reaction, however, the related studies are still in its infancy and the enhancement of efficiency remains a grand challenge. Here, we report that the photocatalytic H evolution activity of quantized indium chalcogenide semiconductors could be dramatically aroused by the co-decoration of transition metal Zn and Cu. Different from the traditional metal ion doping strategies which only focus on narrowing bandgap for robust visible light harvesting, the conduction and valence band are coordinately regulated to realize the bandgap narrowing and the raising of thermodynamic driving force for proton reduction, simultaneously. Therefore, the as-prepared noble metal-free Cu-ZnInS quantum dots (QDs) exhibits extraordinary activity for photocatalytic H evolution. Under optimal conditions, the Cu-ZnInS QDs could produce H with the rate of 144.4 μmol h mg, 480-fold and 6-fold higher than that of pristine InS QDs and Cu-doped InS QDs counterparts respectively, which is even comparable with the state-of-the-art cadmium chalcogenides QDs.
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http://dx.doi.org/10.3390/nano11051115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146827PMC
April 2021

Donnan Dialysis-Osmotic Distillation (DD-OD) Hybrid Process for Selective Ammonium Recovery Driven by Waste Alkali.

Environ Sci Technol 2021 May 27;55(10):7015-7024. Epub 2021 Apr 27.

Key Laboratory of the Three Gorges Reservoir Region's Eco-Environment, Ministry of Education, College of Environment and Ecology, Chongqing University, Chongqing 400045, PR China.

This work proposed an innovative and energy-efficient Donnan Dialysis (DD) and Osmotic Distillation (OD) hybrid process for alkali-driven ammonium recovery from wastewater. The efficiency and feasibility of ammonium removal and recovery from synthetic and real wastewater using NaOH and waste alkali were investigated. Ammonium in the feed first transported across the cation exchange membrane and accumulated in the receiver chamber. It is then deprotonated as ammonia, passing through the gas permeable membrane and finally is fixed as ammonium salt in the acid chamber. Our results indicated that employing waste alkali (red mud leachate) as driving solution led to excellent ammonium recovery performances (recovery efficiency of >80%), comparable to those of NaOH solution. When the initial ammonium concentration was 5 and 50 mM, the waste alkali driven DD-OD process achieved acceptable NH-N flux density of 16.8 and 169 g N m d, at energy cost as low as 8.38 and 2.06 kWh kg N, respectively. Since this alkali driven DD-OD hybrid process is based on solute concentration (or partial pressure) gradient, it could be an energy-effective technology capable of treating wastewaters containing ammonium using waste alkali to realize nutrients recovery in a sustainable manner.
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http://dx.doi.org/10.1021/acs.est.0c08772DOI Listing
May 2021

A novel framework of Bayesian optimal interval design for phase I trials with late-onset toxicities.

Contemp Clin Trials 2021 Jun 18;105:106404. Epub 2021 Apr 18.

Biostatistics and Research Decision Sciences, Merck & Co., Inc., Kenilworth, NJ 07033, USA. Electronic address:

As molecularly targeted agents (MTAs) and immunotherapies have widely demonstrated delayed toxicity profile after multiple treatment cycles, the traditional phase I dose-finding designs may not be appropriate anymore because they just account for the acute toxicities occurring in the early period of treatment. When the dose-limiting toxicity (DLT) assessment window is prolonged to account for late-onset DLTs, it will cause logistic issues if the enrollment is suspended until all the DLT information is collected. We propose a novel framework to estimate the toxicity probability in the scenarios where some patients' DLT information are not complete and then implement the Bayesian optimal interval (BOIN) design to make decisions on dose escalation/de-escalation. Our proposed approach maintains BOIN's transparency by simply comparing the estimated toxicity probability with the escalation/de-escalation boundaries to decide the next dose level. The numerical studies show that our proposed framework can achieve comparable operating characteristics as other dose-finding designs considering late-onset DLTs, thus providing an attractive option of phase I dose-finding clinical trials for MTAs and immunotherapies.
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http://dx.doi.org/10.1016/j.cct.2021.106404DOI Listing
June 2021

Construction of PD1/CD28 chimeric-switch receptor enhances anti-tumor ability of c-Met CAR-T in gastric cancer.

Oncoimmunology 2021 Mar 31;10(1):1901434. Epub 2021 Mar 31.

Lanzhou University Second Hospital, the Second Clinical Medical College of Lanzhou University, Lanzhou, Gansu, China.

Chimeric antigen receptor (CAR) T cell is a promising method in cancer immunotherapy but faces many challenges in solid tumors. One of the major problems was immunosuppression caused by PD-1. In our study, the expression of c-Met in GC was analyzed from TCGA datasets, GC tissues, and cell lines. The c-Met CAR was a second-generation CAR with 4-1BB, cMet-PD1/CD28 CAR was c-Met CAR adding PD1/CD28 chimeric-switch receptor (CSR). In , we measured the changes of different subgroups, phenotypes and PD-1 expression in CAR-T cells. We detected the secretion levels of different cytokines and the killing ability of CAR-Ts. In , we established a xenograft GC model and observed the anti-tumor effect and off-target toxicity of different CAR-Ts. We find that the expression of c-Met was increased in GC. CD3CD8 T cells and CD62LCCR7 central memory T cells (T) were increased in two CAR-Ts. The stimulation of target cells could promote the expression of PD-1 in c-Met CAR-T. Compared with Mock T, the secretion of cytokines as IFN-γ, TNF-α, IL-6, IL-10 secreted by two CAR-Ts was increased, and the killing ability to c-Met positive GC cells was enhanced. The PD1/CD28 CSR could further enhance the killing ability, especially the long-term anti-tumor effect of c-Met CAR-T, and reduce the release level of IL-6. CAR-Ts target c-Met had no obvious off-target toxicity to normal organs. Thus, the PD1/CD28 CSR could further enhance the anti-tumor ability of c-Met CAR-T, and provides a promising design strategy to improve the efficacy of CAR-T in GC.
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http://dx.doi.org/10.1080/2162402X.2021.1901434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018404PMC
March 2021

Nicotinamide phosphoribosyltransferase inhibitor ameliorates mouse aging-induced cognitive impairment.

J Cereb Blood Flow Metab 2021 Apr 4:271678X211006291. Epub 2021 Apr 4.

Departments of Pharmacology and Neurosurgery, the Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang, China.

Nicotinamide phosphoribosyltransferase (NAMPT) is the key enzyme for the synthesis of nicotinamide adenine dinucleotide (NAD) in the salvaging pathway. Though NAMPT inhibitors such as FK866 were originally developed as anti-cancer drugs, they also display neuroprotective effects. Here we show that the administration of FK866 at 0.5 mg/kg (ip, qod) for four weeks, i.e., ∼1% of the dose used for the treatment of cancer, significantly alleviates the aging-induced impairment of cognition and locomotor activity. Mechanistically, FK866 enhanced autophagy, reduced protein aggregation, and inhibited neuroinflammation indicated by decreasing TNFα, IL-6, GFAP, and Iba1 levels in the aged mouse brain. Though FK866 did not affect the total NAD and nicotinamide mononucleotide (NMN) levels in the mouse brain at the dose we used, FK866 increased nicotinamide (NAM) level in the young mouse brain and decreased NAM level in the aged mouse brain. On the other hand, FK866 did not affect the serum glucose, cholesterol, and triglyceride of young and aged mice and exhibited no effects on the various indices of young mice. Thus, the NAMPT inhibitor can be repurpose to counteract the cognitive impairment upon aging. We also envision that NAMPT inhibitor can be used for the treatment of age-related neurodegenerative diseases.
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http://dx.doi.org/10.1177/0271678X211006291DOI Listing
April 2021

The efficacy of manipulation as a treatment for myofascial pelvic pain.

Int Urol Nephrol 2021 Jul 2;53(7):1339-1343. Epub 2021 Apr 2.

Department of Gynecology, Wenzhou Third Clinical Institute Affiliated to Wen Zhou Medical University, Wenzhou People's Hospital, No. 57 of Canghou Street, Lucheng, Wenzhou, 325000, Zhejiang, China.

Objective: To evaluate the effect of myofascial manipulation by observing the changes in pelvic floor myofascial scores and electromyography (EMG) data before and after treatment.

Methods: A total of 106 patients with myofascial pelvic pain (MFPP) were enrolled in a treatment group, and 50 healthy women were enrolled in a control group. The changes in the pelvic floor EMG data in the two groups were monitored by using Myo Trac before and after treatment. Pelvic trigger points and their distribution in the MFPP patients were examined using a finger pressure test. The visual analogue scale was used to assess the severity of pain in both groups. After one course of manipulation (twice per week for a total of 10 times), the effectiveness of the manipulation was analyzed by comparing the changes in pain scores before and after treatment.

Results: The main symptoms of MFPP in the study sample consisted of lower abdominal pain, lumbosacral pain, or mixed pain, which together accounted for 67% of all symptoms. Patients often had multiple trigger points, covering 47.17% of the body. The differences between the treatment group and control group in the changes in pelvic floor muscle strength, number of pain points, pain scores, resting EMG of pelvic floor muscles, and relaxation time after muscle contraction were all statistically significant (P < 0.05). The differences between the pre-treatment and post-treatment groups in the changes in pelvic floor muscle strength, number of pain points, pain scores, resting EMG of pelvic floor muscles, and relaxation time after muscle contraction were all statistically significant (P < 0.05) CONCLUSION: Manipulation is an effective treatment for MFPP and is worthy of further clinical promotion.
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http://dx.doi.org/10.1007/s11255-021-02840-8DOI Listing
July 2021

Hybrid 3D Nanostructure-Based Hole Transport Layer for Highly Efficient Inverted Perovskite Solar Cells.

ACS Appl Mater Interfaces 2021 Apr 30;13(14):16611-16619. Epub 2021 Mar 30.

Department of Electrical and Electronic Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong, 999077, China.

In this study, we demonstrate a new hybrid three-dimensional (3D) nanostructure system as an efficient hole transport layer (HTL) by a facile design of a low-temperature solution process. It is realized by integrating high-conductive chromium-doped CuGaO nanoplates synthesized with choline chloride (denoted as Cr/CuGaO-CC) into ultrasmall NiO nanoparticles. First, we propose to incorporate a Cr-doped strategy under hydrothermal synthesis conditions together with controllable intermediates and surfactants' assistance to synthesize fine-sized Cr/CuGaO-CC nanoplates. Subsequently, these two-dimensional (2D) nanoplates serve as the expressway for improving hole transportation/extraction properties. Meanwhile, the ultrasmall-sized NiO nanoparticles are employed to modify the surface for achieving unique surface properties. The HTL formed from the designed hybrid 3D-nanostructured system exhibits the advantages of smooth and full-covered surface, remarkable charge collection efficiency, energy level alignment between the electrode and perovskite layer, and the promotion of perovskite crystal growth. Consequently, nearly 20% of power conversion efficiency with negligible hysteresis is achieved in inverted perovskite solar cells (PSCs). This work not only demonstrates the potential applications of a 3D-nanostructured Cr/CuGaO-CC/NiO hybrid HTL in PSCs but also provides a fundamental insight into the design of hybrid material systems by manipulating electric behavior and morphology structure for achieving high-performance photovoltaic devices.
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http://dx.doi.org/10.1021/acsami.0c21064DOI Listing
April 2021

Improving diacetyl production in Corynebacterium glutamicum via modifying respiratory chain.

J Biotechnol 2021 May 23;332:20-28. Epub 2021 Mar 23.

Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), SynBio Research Platform, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300350, China. Electronic address:

To explore the suitability of Corynebacterium glutamicum as a chassis for diacetyl production from glucose, diacetyl metabolic pathway and the respiratory chain were linked to achieve redox balance. The carbon flux was redirected from pyruvate to diacetyl by overexpressing the α-acetolactate synthase, in combination with disruption the biosynthetic pathways of lactate, acetoin, 2,3-butanediol and acetate in C. glutamicum ATCC 13032. These modifications resulted in a sharp increase of the NADH/NAD ratio from 0.53 to 1.10, and produced 0.58 g/L diacetyl under aerobic conditions, representing a 58-fold increase over the wild type. Although the modification of the by-product pathways is an effective strategy, these disruption led to intracellular cofactor imbalance. NADH re-oxidization was further successfully solved by overexpressing of cytochrome bd oxidase. We constructed an efficient respiration-dependent cell factory by modification of the respiratory chain, improving diacetyl titer to 1.29 g/L in CGC11, decreased NADH/NAD ratio to 0.45, increased the ATP concentration from 8.51 to 10.64 μM/gDCW. To our best knowledge, this is the first report of diacetyl synthesis in C. glutamicum. Intracellular cofactor imbalance can be reduced by modification of the respiratory chain for production of diacetyl as well as other bio-based products with cofactor imbalance in C. glutamicum.
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http://dx.doi.org/10.1016/j.jbiotec.2021.03.014DOI Listing
May 2021

Randomized controlled clinical study on Yiqi Liangxue Shengji prescription for intervention cardiac function of acute myocardial infarction with ischemia-reperfusion injury.

Medicine (Baltimore) 2021 Mar;100(10):e24944

Department of Cardiology, Dongfang Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, China.

Introduction: The morbidity and mortality of acute myocardial infarction patients still remains high after percutaneous coronary intervention (PCI). Myocardial ischemia-reperfusion (MIR) injury is one of the important reasons. Although the phenomenon of MIR injury can paradoxically reduce the beneficial effects of myocardial reperfusion, there currently remains no effective therapeutic agent for preventing MIR. Previous studies have shown that Yiqi Liangxue Shengji prescription (YLS) is effective in improving clinical symptoms and ameliorating the major adverse cardiovascular events of coronary heart disease patients undergoing PCI. This study aims to evaluate the effectiveness and safety of YLS in patients with acute myocardial infarction (AMI) after PCI.

Methods: This study is a randomized, double-blinded, placebo-controlled, single-central clinical trial. A total of 140 participants are randomly allocated to 2 groups: the intervention group and the placebo group. Based on routine medications, the intervention group will be treated with YLS and the placebo group will be treated with YLS placebo. All participants will receive a 8-week treatment and then be followed up for another 12 months. The primary outcome measures are N terminal pro B type natriuretic peptide (NT-proBNP) and left ventricular ejection fraction. Secondary outcomes are plasma levels of microRNA-145, plasma cardiac enzyme, and Troponin I levels in blood samples, changes in ST-segment in ECG, Seattle Angina Questionnaire, the efficacy of angina symptoms, and occurrence of major adverse cardiac events. All the data will be recorded in case report forms and analyzed by SPSS V.17.0.

Discussion: The trial will investigate whether the postoperative administration of YLS in patients with AMI after PCI will improve cardiac function. And it explores microRNAs (miRNA)-145 as detection of blood-based biomarkers for AMI by evaluating the relation between miRNAs in plasma and cardiac function.

Trial Registration: Chinese Clinical Trials Registry identifier ChiCTR2000038816. Registered on October 10, 2020.
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http://dx.doi.org/10.1097/MD.0000000000024944DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969256PMC
March 2021

Estimation of treatment effect in 2-in-1 adaptive design and some of its extensions.

Stat Med 2021 May 15;40(11):2556-2577. Epub 2021 Mar 15.

Biostatistics and Research Decision Sciences, MRL, Merck & Co., Inc, Kenilworth, New Jersey, USA.

The 2-in-1 adaptive design allows seamless expansion of an ongoing Phase II trial into a Phase III trial to expedite a drug development program. Since its publication, it has generated a lot of interest. So far, most of the related research focused on type I error control. Similar to most adaptive designs, 2-in-1 design could also pose a great challenge on estimation of treatment effect due to the data-driven adaptation. In addition, the use of intermediate endpoint for interim adaptive decision-making is a less well-studied field. In this paper, we investigate the bias and variances in estimation for 2-in-1 design and some of its extensions, and propose some bias-adjusted estimators for 2-in-1 design. The properties of the proposed estimators are further studied theoretically and/or numerically, so as to provide guidance on how to interpret the estimated treatment effect of 2-in-1 design.
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http://dx.doi.org/10.1002/sim.8917DOI Listing
May 2021

Operating status of public toilets in the Hutong neighborhoods of Beijing: An empirical study.

J Environ Manage 2021 Jun 10;287:112252. Epub 2021 Mar 10.

School of Energy and Environmental Engineering, Beijing Key Laboratory of Resource-oriented Treatment of Industrial Pollutants, University of Science and Technology Beijing, Xueyuan Road No.30, Haidian District, Beijing, 100083, PR China. Electronic address:

The provision of sanitation services for fast-growing urban populations is one of the world's urgent challenges. Hutong neighborhoods in Beijing, capital of China, cannot be rebuilt due to the protection of historical heritage, while residents still need to keep the habit of defecating in public toilets. One hundred public toilets with non-sewered sanitation in the Hutong neighborhoods of Beijing were visited to investigate the actual operating status in response to the "toilet revolution" campaign. The fault tree approach was used to identify the barriers toward a decent and environment-friendly public toilet and evaluate potential risks from the malfunction of various components. Four subsystems are defined and elaborated to calculate the fault possibility. These subsystems are environment- and user-friendly, regarded as ancillary facilities, and used for fecal sludge (FS) management. Statistical analysis of targeted cases indicated that fault probabilities of environmental considerations, user-friendly considerations, ancillary facilities, FS management are calculated as 0.79, 0.96, 0.96, and 0, respectively. The subsystems were weighted using a Delphi method concept. Results showed that the well operation ratio of Beijing Hutong public toilets is only 32%, and the sanitation service value chain can be further optimized. This study also provides references for other countries, which are dedicated to promoting urban sanitation and public health.
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http://dx.doi.org/10.1016/j.jenvman.2021.112252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075803PMC
June 2021

Modulating oxygen vacancies on bismuth-molybdate hierarchical hollow microspheres for photocatalytic selective alcohol oxidation with hydrogen peroxide production.

J Colloid Interface Sci 2021 Jun 16;592:1-12. Epub 2021 Feb 16.

Department of Chemistry, School of Science, Zhejiang Sci-Tech University, No. 928 Second Avenue, Xiasha Higher Education Zone, Hangzhou 310018, China. Electronic address:

Photocatalytic selective oxidation of alcohols into high value-added carbonyl compounds accompanied by producing hydrogen peroxide (HO) is undoubtedly a more efficient solar energy conversion strategy with high atom economy. Herein, we have developed an efficient photocatalyst of bismuth-molybdate (BiMoO) hierarchical hollow microspheres with tunable surface oxygen vacancies (OVs) for promoting the photocatalytic selective alcohol oxidation with HO production. The effect of surface OVs on the photocatalytic efficiency is studied systematically by comparing the performance of different photocatalysts. The benzaldehyde and HO production rates over the OV-rich BiMoO photocatalyst reach up to 1310 and 67.2 μmol g h, respectively, which are 2.3 and 4.0 times those generated from the OV-poor BiMoO hollow microspheres. The roles of various active radicals in the photocatalytic reaction are probed by a series of controlled experiments and in situ ESR measurements, revealing that both superoxide radical (•O) and carbon-centered radical are the key active intermediates. The introduction of surface OVs on BiMoO hollow microspheres accelerates the separation and transfer of photo-generated charge carriers as well as enhances the adsorption and activation of reactant molecules, thereby greatly promoting the photocatalytic selective oxidation of alcohols along with HO production. This work not only demonstrates a facile strategy for the preparation of high-efficiency photocatalysts by simultaneous modulations of morphology and surface defects, but also offers insight into developing the dual-functional photocatalytic reactions for the full utilizations of photoinduced electrons and holes.
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http://dx.doi.org/10.1016/j.jcis.2021.02.036DOI Listing
June 2021

Evaluation of endometrial immune status of polycystic ovary syndrome.

J Reprod Immunol 2021 04 2;144:103282. Epub 2021 Feb 2.

Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen, China. Electronic address:

Polycystic ovary syndrome (PCOS) is described as a low-grade chronic inflammatory state. However, there are limited studies on the specific endometrial immune status of PCOS patients. Whether this endometrial immune cell pattern is intrinsic to PCOS or the consequence of PCOS-associated obesity is a subject of debate. This study retrospectively included one hundred women diagnosed with PCOS and ninety-five normal fertile controls, which further divided into four groups (normoweight PCOS; overweight PCOS; normoweight control; overweight control) based on body mass index. The percentages of endometrial CD68 macrophages (1.97 % vs. 1.17 %; P < 0.001), CD163 M2 macrophages (2.30 % vs. 1.83 %; P = 0.001), CD1a iDCs (0.044 % vs. 0.029 %; P = 0.002), CD83 mDCs (1.72 % vs. 1.07 %; P < 0.001) and CD8 T cells (2.82 % vs. 1.95 %; P < 0.001) were significantly higher in normoweight PCOS women than normoweight controls. The percentage of CD68 macrophages (2.09 % vs. 1.15 %; P < 0.001) was significantly higher in overweight PCOS women compared with overweight controls. In multivariant linear regression analysis, participants' PCOS status was the main predictors of endometrial CD68 macrophages, CD163 M2 macrophages, CD1a iDCs, CD83 mDCs and CD8 T cells in the whole study population. Additionally, in PCOS group, positive correlations were found between endometrial CD56 NK, CD163 M2 macrophages and QUICKI, indicating there was an association between endometrial immune cells and insulin resistance in PCOS women. Our study suggests that women with PCOS have altered endometrial immune cells, which may reflect a state of chronic low grade inflammation. The chronic inflammation, independent of obesity, may help understand the pathophysiologic mechanisms of intrinsic PCOS.
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http://dx.doi.org/10.1016/j.jri.2021.103282DOI Listing
April 2021

CDK6 Is a Potential Prognostic Biomarker in Acute Myeloid Leukemia.

Front Genet 2020 1;11:600227. Epub 2021 Feb 1.

Department of Hematology, The First Affiliated Hospital of Jinan University, Guangzhou, China.

Acute myeloid leukemia (AML) is a threatening hematological malignant disease in which new successful approaches in therapy are needed. Cyclin-dependent kinase 6 (), a regulatory enzyme of the cell cycle that plays an important role in leukemogenesis and the maintenance of leukemia stem cells (LSC), has the potential to predict the prognosis of AML. By analyzing public databases, we observed that the messenger RNA (mRNA) levels of were significantly overexpressed in AML cell lines and non-acute promyelocytic leukemia (non-APL) AML patients when compared to healthy donors. Furthermore, expression was significantly reduced in AML patients who achieved complete remission (CR) compared to that at the time of diagnosis in our validated cohort. The expression of was tightly correlated with peripheral blood blasts, French-American-British (FAB) subtypes, CCAAT-enhancer-binding protein α (CEBPA) mutation, and chromosomal abnormalities of t(8;21). However, the clinical significance and effects of expression on the prognosis of non-APL AML patients remain uncertain. We found that expression was inversely correlated with overall survival (OS) among non-APL AML patients using the Kaplan-Meier analysis. was also found to be positively associated with genes identified to contribute to the development of leukemia, including , , , and , as well as being negatively associated with anticancer microRNAs, including miR-187, miR-9, miR-582, miR708, and miR-362. In summary, our study revealed that might be a potential diagnostic and prognostic biomarker in non-APL AML patients.
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http://dx.doi.org/10.3389/fgene.2020.600227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882723PMC
February 2021

Profiles of alternative splicing landscape in breast cancer and their clinical significance: an integrative analysis based on large-sequencing data.

Ann Transl Med 2021 Jan;9(1):58

Department of General Surgery, Zhongshan Hospital, Fudan University & State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, China.

Background: Alternative splicing (AS) is closely correlated with the initiation and progression of carcinoma. The systematic analysis of its biological and clinical significance in breast cancer (BRCA) is, however, lacking.

Methods: Clinical data and RNA-seq were obtained from the TCGA dataset and differentially expressed AS (DEAS) events between tumor and paired normal BRCA tissues were identified. Enrichment analysis was then used to reveal the potential biological functions of DEAS events. We performed protein-protein interaction (PPI) analysis of DEAS events by using STRING and the correlation network between splicing factors (SFs) and AS events was constructed. The LASSO Cox model, Kaplan-Meier and log-rank tests were used to construct and evaluate DEAS-related risk signature, and the association between DEAS events and clinicopathological features were then analyzed.

Results: After strict filtering, 35,367 AS events and 973 DEAS events were detected. DEAS corresponding genes were significantly enriched in pivotal pathways including cell adhesion, cytoskeleton organization, and extracellular matrix organization. A total of 103 DEAS events were correlated with disease free survival. The DEAS-related risk signature stratified BRCA patients into two groups and the area under curve (AUC) was 0.754. Moreover, patients in the high-risk group had enriched basel-like subtype, advanced clinical stages, proliferation, and metastasis potency.

Conclusions: Collectively, the profile of DEAS landscape in BRCA revealed the potential biological function and prognostic value of DEAS events.
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http://dx.doi.org/10.21037/atm-20-7203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859793PMC
January 2021

Enhancement of lateral connectivity promotes the establishment of plants in saltmarshes.

Sci Total Environ 2021 May 30;767:145484. Epub 2021 Jan 30.

Research and Development Center for Watershed Environmental Eco-Engineering, Beijing Normal University, Zhuhai 519087, China; State Key Laboratory of Water Environment Simulation, School of Environment, Beijing Normal University, 100875 Beijing, China; Yellow River Estuary Wetland Ecosystem Observation and Research Station, Ministry of Education, Shandong 257500, China. Electronic address:

Several studies have shown that enhancing lateral hydrological connectivity in river systems can increase the exchange of materials and energy, and improves species diversity, which suggests that it might be a useful ecological restoration tool. The variation in elevation gradient across a saltmarsh system is small, which means that lateral hydrological connectivity in saltmarsh systems is often ignored and the ecological effects caused by the variation in lateral hydrological connectivity are seldom studied. Lateral hydrological connectivity presents when a hydrological connection between marsh plain and tidal creek occurs, as a time interval during which tidal flow occurred. This study explored the effects of enhancing lateral hydrological connectivity on the plant life history process using empirical studies. The enhancement of lateral hydrological connectivity on a temporal scale was achieved by placing hollowed microtopographic structures on the marsh. Data obtained through the high-frequency monitoring of tidal levels was used to calculate lateral hydrological connectivity enhancement, and field control experiments were used to determine the effects of lateral connectivity enhancement on seed retention, emergence, and seedling survival at each life stage. The results showed that lateral hydrological connectivity decreased with the increasing distance to sea and the lateral distance to tidal creek. The hollowed microtopographic structures significantly enhanced lateral hydrological connectivity on the marsh, increased soil moisture content, and reduced soil salinity. Furthermore, seed retention time was significantly increased during dispersal stage, and potential seed establishment was improved. During the emergence and growth stages, the enhanced soil moisture and reduced salinity facilitated the emergence and growth of seeds and seedlings. These effects benefit plant re-establishment in bare areas, especially in areas with low lateral hydrological connectivity. This information could be used to improve the restoration or recovery of vegetation on bare or degraded saltmarshes.
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http://dx.doi.org/10.1016/j.scitotenv.2021.145484DOI Listing
May 2021

Insights into chemosensory genes of Pagiophloeus tsushimanus adults using transcriptome and qRT-PCR analysis.

Comp Biochem Physiol Part D Genomics Proteomics 2021 Mar 3;37:100785. Epub 2021 Feb 3.

Co-Innovation Center for Sustainable Forestry in Southern China, Nanjing Forestry University, Nanjing, Jiangsu, China; College of Forestry, Nanjing Forestry University, Nanjing, Jiangsu, China. Electronic address:

Pagiophloeus tsushimanus is a new, destructive, and monophagous weevil pest that thrives on Cinnamomum camphora, found in Shanghai. The functions of chemosensory genes involved in the host location and intraspecific communication of P. tsushimanus remain unknown. The male-female transcriptomes of P. tsushimanus adults were assembled using Illumina sequencing, and we focused on all chemosensory genes in transcriptomes. In general, 58,088 unigenes with a mean length of 1018.19 bp were obtained. In total, 39 odorant binding proteins (OBPs), 10 chemosensory proteins (CSPs), 22 olfactory receptors (ORs), 16 gustatory receptors (GRs), eight ionotropic receptors (IRs), and five sensory neuron membrane proteins (SNMPs) were identified. PtsuOBPs comprised four subfamilies (20 Minus-C, one Plus-C, two Dimer, and 15 Classic). Both PtsuOBPs and PtsuCSPs contained a highly conserved sequence motif of cysteine residues. PtsuORs including one olfactory receptor co-receptors (Ptsu/Orco) comprised seven predicted transmembrane domains. Phylogenetic analysis revealed that PtsuOBPs, PtsuCSPs, and PtsuORs in P. tsushimanus exhibited low homology compared to other insect species. The results of tissue- and sex-specific expression patterns indicated that PtsuOBPs and PtsuORs were highly abundant in the antennae; whereas, PtsuCSPs were not only highly abundant in antennae, but also abdominal apexes, wings, and legs. In conclusion, these results enrich the gene database of P. tsushimanus, which may serve as a basis for identifying novel targets to disrupt olfactory key genes and may provide a reverse validation method to identify attractants for formulating potential eco-friendly control strategies for this pest.
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http://dx.doi.org/10.1016/j.cbd.2020.100785DOI Listing
March 2021