Publications by authors named "Hongyan Zhang"

502 Publications

The central nervous system can directly regulate breast cancer progression and blockage by quercetin.

Ann Transl Med 2021 Jun;9(12):999

Department of Breast, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China.

Background: Neuroinflammation involving the central nervous system (CNS), such as depression, is associated with a significantly increased risk of cancer and cancer-specific mortality due to breast cancer. It is of great significance to learn about the regulatory process of CNS in breast cancer progression.

Methods: We established a depressive MMTV-PyVT mouse model. The expression levels of neurotransmitters in the serum of depression animal models were assessed by enzyme-linked immunosorbent assay (ELISA). Changes of the microglia cells in the mice's brains were evaluated by immunofluorescence and reverse transcription-polymerase chain reaction (RT-PCR). Breast cancer progression was assessed by immunohistochemistry (IHC) analysis. To further investigate the mechanism by which ant-depressant drugs disrupt breast cancer progression, protein sequencing and network pharmacology were applied to identify related targets. Furthermore, we used conditioned medium from BV-2 microglia to culture breast cancer cells and treated the cells with quercetin at different concentrations; cell viability was assessed by the MTT assay.

Results: Our results show a possible regulatory target between neuroinflammation in the CNS and development of breast cancer, along with the reversal effect of quercetin on breast cancer progression.

Conclusions: Chronic stress may be an indicator of breast cancer and that quercetin could be an effective treatment for breast cancer patients with chronic stress.
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http://dx.doi.org/10.21037/atm-21-2558DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267261PMC
June 2021

Potential role of glutathione S-transferase P1 gene polymorphism and metabolic syndrome in lower urinary tract symptoms attributed to benign prostatic hyperplasia.

World J Urol 2021 Jul 6. Epub 2021 Jul 6.

Department of Urology, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China.

Objective: The aim of the study is to investigate the effects of glutathione S-transferase P1 (GSTP1) gene polymorphism and metabolic syndrome (MS) on lower urinary tract symptoms (LUTS) attributed to benign prostatic hyperplasia (BPH).

Methods: This study included 195 patients diagnosed with LUTS secondary to BPH as case group, divided into simple BPH group (S-BPH group) and combined with MS group (MS-BPH group). Control group included 200 healthy elderly men without LUTS. Use peripheral blood samples detected the GSTP1 gene polymorphism (Ile 105 Val A → G polymorphism) by polymerase chain reaction-restriction fragment length polymorphism. Recorded age, GSTP1 gene polymorphism, international prostate symptom score (IPSS), prostate volume (PV), residual urine volume (RV), maximal urinary flowrate (Qmax), and prostate-specific antigen (PSA) to statistical analysis.

Results: Pairwise compared between control group, S-BPH group and MS-BPH, the PV (P < 0.001), PSA (P < 0.001), RV (P < 0.001), Qmax (P < 0.001), IPSS (P < 0.001), frequencies of GSTP1 gene (P < 0.05) were shown significant different, and MS-BPH group had larger PV, and more severe LUTS. In case group, variation genotypes (GSTP1 A/G + G/G) always had larger PV, higher PSA and IPSS, more RV and lower Qmax than homozygote (GSTP1 A/A) and the comparison were significant different (P < 0.05). Variation genotypes were positively correlated with PV (β = 0.092, P < 0.001), RV (β = 0.228, P = 0.004), IPSS (β = 0.274, P = 0.038), PSA (β = 1.243, P < 0.001) and negatively correlated with Qmax (β = -0.362, P = 0.025).

Conclusion: In patients with BPH, GSTP1 variation genotypes and MS might be potential risk factors for faster progression of benign prostatic enlargement and LUTS, which might increase the surgical rate.

Trial Registration: ChiCTR-IPR-14005580.
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http://dx.doi.org/10.1007/s00345-021-03778-3DOI Listing
July 2021

ESCNet: An End-to-End Superpixel-Enhanced Change Detection Network for Very-High-Resolution Remote Sensing Images.

IEEE Trans Neural Netw Learn Syst 2021 Jul 5;PP. Epub 2021 Jul 5.

Change detection (CD), as one of the central problems in Earth observation, has attracted a lot of research interest over recent decades. Due to the rapid development of satellite sensors in recent years, we have witnessed an enrichment of the CD source data with the availability of very-high-resolution (VHR) multispectral imagery, which provides abundant change clues. However, precisely locating real changed areas still remains a challenge. In this article, we propose an end-to-end superpixel-enhanced CD network (ESCNet) for VHR images, which combines differentiable superpixel segmentation and a deep convolutional neural network (DCNN). Two weight-sharing superpixel sampling networks (SSNs) are tailored for the feature extraction and superpixel segmentation of bitemporal image pairs. A UNet-based Siamese neural network is then employed to mine the different information. The superpixels are then leveraged to reduce the latent noise in the pixel-level feature maps while preserving the edges, where a novel superpixelation module is used to serve this purpose. Furthermore, to compensate for the dependence on the number of superpixels, we propose an innovative adaptive superpixel merging (ASM) module, which has a concise form and is fully differentiable. A pixel-level refinement module making use of the multilevel decoded features is also appended to the end of the framework. Experiments on two public datasets confirmed the superiority of ESCNet compared to the traditional and state-of-the-art (SOTA) deep learning-based CD (DLCD) methods.
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http://dx.doi.org/10.1109/TNNLS.2021.3089332DOI Listing
July 2021

Identification of a novel variant erythrocyte surface antigen-1 (VESA1) in Babesia orientalis.

Parasitol Res 2021 Jul 5. Epub 2021 Jul 5.

State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, Hubei, China.

Babesia orientalis, belonging to the phylum Apicomplexa, is mainly accountable for water buffalo babesiosis, which adversely affected the livestock industry in China. Variant erythrocyte surface antigen-1 (VESA1), an antigen that helps infected erythrocytes to escape from host immune responses, was first reported in Babesia bovis. Various VESA1 proteins have also been characterized in other Babesia species. Nevertheless, there is no research on the identification and characterization of VESA1 proteins in Babesia orientalis. In this study, the BoVESA1 gene was amplified from both gDNA and cDNA. The results revealed that it is an intronless gene with a full length of 753 bp, encoding a protein of 250 amino acids with a predicted molecular weight of 28 kDa. The coding sequence (CDS) was cloned into the pGEX-6p-1 vector using a homologous recombination kit and expressed as a glutathione-S-transferase (GST)-fusion protein with a molecular weight of 53 kDa. The tertiary structure of BoVESA1 was predicted using the I-TASSER software. The recombinant protein was subjected to western blotting; the immunogenicity of recombinant BoVESA1 (rBoVESA1) was identified by incubating it with B. orientalis-positive serum. The native BoVESA1 was identified using the lysates of B. orientalis-infected water buffalo erythrocytes incubated with the anti-rBoVESA1 mouse serum. The results showed a band of ~ 28 kDa, which is similar to the predicted size. Immunofluorescence assay (IFA) using anti-rBoVESA1 serum probed indicated a strong signal in the infected RBCs, while the negative control showed no signal. In conclusion, the VESA1 protein was first identified in B. orientalis. This study facilitated further investigation of B. orientalis, and the results indicated that BoVESA1 may serve as a potential candidate antigen for diagnosis and detection of B. orientalis infection.
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http://dx.doi.org/10.1007/s00436-021-07194-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255115PMC
July 2021

Intracellular AGR2 transduces PGE2 stimuli to promote epithelial-mesenchymal transition and metastasis of colorectal cancer.

Cancer Lett 2021 Jun 30;518:180-195. Epub 2021 Jun 30.

Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, China; Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, China. Electronic address:

Human anterior gradient homolog 2 (AGR2) reportedly acts as an oncogene in multiple types of cancers. As a secreted protein, the oncogenic roles of extracellular AGR2 have been the focus of the increasing number of studies. In contrast, the oncological functions of intracellular AGR2 (iAGR2) remain elusive. Here, we report that intracellular AGR2 (iAGR2) is sufficient to promote CRC metastasis. iAGR2 binds to KDEL receptors (KDELRs) via its KTEL motif to activate downstream Gs-PKA signaling. Activated PKA upregulates the expression of NF-κB subunit c-Rel (REL) and acetylates histone H3 at lysine 9 (H3K9ac) to promote the transcription of SNAIL and SLUG. AGR2 can be upregulated by prostaglandin E2 (PGE2) via EP4-PI3K-AKT pathway and is indispensable for PGE2-induced CRC metastasis. AGR2 knockdown enhances therapeutic effects of a COX-2 inhibitor, celecoxib, in CRC metastasis. Collectively, our study reveals a promoting role and molecular mechanisms of iAGR2 in CRC metastasis and uncovers a new tumor microenvironment signal regulating AGR2 expression, which may provide new targets for treating metastatic CRC.
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http://dx.doi.org/10.1016/j.canlet.2021.06.025DOI Listing
June 2021

[Rapid screening of illegally added poppy husk in hot pot sauce and soup by thermal desorption electrospray ionization-triple quadruple mass spectrometry].

Se Pu 2020 Jul;38(7):861-867

Lanzhou Institute for Food and Drug Control, Lanzhou 730050, China.

A thermal desorption electrospray ionization-triple quadruple mass spectrometry (TD-ESI-MS/MS) method was developed for the rapid screening of poppy husk in hot pot sauce and soup. The solid surface or liquid sample was directly touched by a simple metal probe. The analytes collected on the probe were desorbed and ionized using a TD-ESI source, after which the analyte ions were detected by MS/MS in multiple reaction monitoring (MRM) mode. The results were compared with those of colloidal gold card rapid detection and verified by high performance liquid chromatography coupled with triple quadrupole mass spectrometry (HPLC-MS/MS). The instrument gave the best response with the highest sensitivity under the following conditions: thermal desorption temperature, 260 ℃; injection solvent, 0.1% formic acid aqueous solution containing 10 mmol/L formic ammonium-acetonitrile (1:1, v/v); flow rate, 200 μL/h. The limits of detection (LODs) for papaverine, noscapine, and thebaine in five alkaloids were 2 μg/kg, while those for codeine and morphine were 10 μg/kg in hot pot sauce and 5 μg/kg in soup. The sensitivity of this method was significantly superior to that of the colloidal gold card rapid detection. The method was applied to 50 batches of hot pot sauce and soup. Noscapine, papaverine, thebaine, and morphine were detected in a positive sample of chicken soup, which was consistent with the result of the HPLC-MS/MS method. This method without sample preparation and chromatographic separation is fast, green, and environmentally benign, thus being suitable for the rapid qualitative analysis of poppy husk in food.
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http://dx.doi.org/10.3724/SP.J.1123.2020.02002DOI Listing
July 2020

[Preparation of core-shell silica-carbon composite microspheres stationary phase and application in saccharide separation].

Se Pu 2020 Dec;38(12):1357-1362

Laboratory of High-Resolution Mass Spectrometry Technologies, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.

In this study, core-shell mesoporous silica-carbon composite microspheres ([email protected]) were prepared by one-step coating of the phenol formaldehyde polymer (PF) on SiO surface and by carbonizing the PF polymer under nitrogen atmosphere. The morphology observation of the [email protected] stationary phase showed that it had good monodispersity. Surface area (302 m/g), mean pore diameter (9.5 nm), and pore volume (0.63 cm/g) of [email protected] materials were also measured by pore structure analysis. The results showed that the [email protected] was successfully immobilized on the silica particles via copolymerization and carbonization. As a stationary phase of HPLC, the [email protected] column was filled by a slurry method. The [email protected] materials formed after calcination of SiO coated with phenolic resin could be used for the separation of four polar sugar compounds (D-(+)-glucosamine hydrochloride, glucose, D-(+)-trehalose dihydrat and raffinose) with the mobile phase of acetonitrile-water (containing 0.1% (v/v) formic acid). However, the material formed by calcinating SiO without coating phenolic resin could not separate these polar sugar compounds by HPLC-MS. Finally, the representative oligosaccharide isomers of raffinose, melezitose and stachyose, nystose, and human milk oligosaccharide isomers, such as 3'-sialyllactose, 6'-sialyllactose and lacto--newtetraose, lacto--tetraose, were successfully separated by the [email protected] column with good peak shapes. The results demonstrates that silica-carbon composites derived from phenolic resin have potential application in polar compounds chromatographic separation.
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http://dx.doi.org/10.3724/SP.J.1123.2020.08016DOI Listing
December 2020

Epitranscriptomic editing of the RNA N6-methyladenosine modification by dCasRx conjugated methyltransferase and demethylase.

Nucleic Acids Res 2021 07;49(13):7361-7374

Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, 310024, China.

N6-methyladenosine (m6A) is a common modification on endogenous RNA transcripts in mammalian cells. Technologies to precisely modify the RNA m6A levels at specific transcriptomic loci empower interrogation of biological functions of epitranscriptomic modifications. Here, we developed a bidirectional dCasRx epitranscriptome editing platform composed of a nuclear-localized dCasRx conjugated with either a methyltransferase, METTL3, or a demethylase, ALKBH5, to manipulate methylation events at targeted m6A sites. Leveraging this platform, we specifically and efficiently edited m6A modifications at targeted sites, reflected in gene expression and cell proliferation. We employed the dCasRx epitranscriptomic editor system to elucidate the molecular function of m6A-binding proteins YTHDF paralogs (YTHDF1, YTHDF2 and YTHDF3), revealing that YTHDFs promote m6A-mediated mRNA degradation. Collectively, our dCasRx epitranscriptome perturbation platform permits site-specific m6A editing for delineating of functional roles of individual m6A modifications in the mammalian epitranscriptome.
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http://dx.doi.org/10.1093/nar/gkab517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287920PMC
July 2021

Acupuncture for Breast Cancer: A Systematic Review and Meta-Analysis of Patient-Reported Outcomes.

Front Oncol 2021 10;11:646315. Epub 2021 Jun 10.

Breast Clinic Center, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China.

Abstract: The present systematic review and meta-analysis was undertaken to evaluate the effects of acupuncture in women with breast cancer (BC), focusing on patient-reported outcomes (PROs).

Methods: A comprehensive literature search was carried out for randomized controlled trials (RCTs) reporting PROs in BC patients with treatment-related symptoms after undergoing acupuncture for at least four weeks. Literature screening, data extraction, and risk bias assessment were independently carried out by two researchers.

Results: Out of the 2, 524 identified studies, 29 studies representing 33 articles were included in this meta-analysis. At the end of treatment (EOT), the acupuncture patients' quality of life (QoL) was measured by the QLQ-C30 QoL subscale, the Functional Assessment of Cancer Therapy-Endocrine Symptoms (FACT-ES), the Functional Assessment of Cancer Therapy-General/Breast (FACT-G/B), and the Menopause-Specific Quality of Life Questionnaire (MENQOL), which depicted a significant improvement. The use of acupuncture in BC patients lead to a considerable reduction in the scores of all subscales of the Brief Pain Inventory-Short Form (BPI-SF) and Visual Analog Scale (VAS) measuring pain. Moreover, patients treated with acupuncture were more likely to experience improvements in hot flashes scores, fatigue, sleep disturbance, and anxiety compared to those in the control group, while the improvements in depression were comparable across both groups. Long-term follow-up results were similar to the EOT results.

Conclusions: Current evidence suggests that acupuncture might improve BC treatment-related symptoms measured with PROs including QoL, pain, fatigue, hot flashes, sleep disturbance and anxiety. However, a number of included studies report limited amounts of certain subgroup settings, thus more rigorous, well-designed and larger RCTs are needed to confirm our results.
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http://dx.doi.org/10.3389/fonc.2021.646315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222976PMC
June 2021

Metastasis pattern and prognosis in men with esophageal cancer patients: A SEER-based study.

Medicine (Baltimore) 2021 Jun;100(25):e26496

Department of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin.

Abstract: Esophageal cancer (EC) is relatively common; at the time of diagnosis, 50% of cases present with distant metastases, and most patients are men. This study aimed to examine and compare the clinicopathological characteristics and metastatic patterns of male EC (MEC) and female EC (FEC). In addition, risk factors associated with MEC prognosis were evaluated.The present study population was extracted from the Surveillance Epidemiology and End Results database. MEC characteristics and factors associated with prognosis were evaluated using descriptive analysis, the Kaplan-Meier method, and the Cox regression model.A total of 12,558 MEC cases were included; among them, 3454 cases had distant organ metastases. Overall, 27.5% of the entire cohort were patients with distant organ metastases. Compared with patients with non-metastatic MEC, patients with metastatic MEC were more likely to be aged ≤60 years, of Black and White race, have a primary lesion in the overlapping esophagus segments, and have a diagnosis of adenocarcinoma of poorly differentiated and undifferentiated grade that was treated with radiotherapy and chemotherapy rather than surgery; moreover, they were also more likely to be married and insured. In addition, patients with MEC were more likely to be aged ≤60 years, White race, and diagnosed with a primary lesion in the lower third of the esophagus and overlapping esophagus segments, and treated without chemotherapy, compared with those with FEC. Patients in the former group were also more likely than those in the latter group to be unmarried and have bone metastasis only and lung metastasis only. Liver, lung, and bone metastases separately, and simultaneous liver and lung metastases were associated with poor survival in MEC patients.Metastatic MEC is associated with clinicopathological characteristics and metastatic patterns different from those associated with non-metastatic MEC and metastatic FEC. Metastatic MEC and FEC patients may have similar prognoses. Distant organ metastasis may be associated with poor prognosis in patients with MEC and FEC.
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http://dx.doi.org/10.1097/MD.0000000000026496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238299PMC
June 2021

Effects of Aster B-mediated intracellular accumulation of cholesterol on inflammatory process and myocardial cell in acute myocardial infarction.

Hellenic J Cardiol 2021 Jun 17. Epub 2021 Jun 17.

Department of Environment and Occupational health, School of Public Health, Qiqihar Medical University, Qiqihar 161006, China. Electronic address:

Background: To explore the effect of cholesterol accumulation in cells on the inflammatory process of acute myocardial infarction and cardiomyocytes and its mechanism.

Methods: Blood samples of 15 patients with myocardial infarction were clinically collected to detect enzyme levels of cholesterol and related myocardial in the serum. Correlation analysis was carried out. On the cellular level, simulation of cholesterol entry and exit cells was conducted by a liposome loaded cholesterol model in this study, and BNP and inflammatory factors were detected with enzyme-linked immunosorbent assay. Moreover, to explore the molecular mechanism of myocardial damage caused by cholesterol, Gramd1b and Prkaca of HL-1 were knocked down with small interference RNA technique. Then inhibitor C3 was used to weaken RhoA activity to explore the level of cardiac muscle cell BNP, so as to identify key protein target site that may be involved in the process of cholesterol damage to cardiac muscle cells.

Results: Serum cholesterol concentration has a significantly positive correlation with the levels of AST, CK, and LD in serum of patients with myocardial infarction. Cholesterol accumulation in cardiac muscle cells can result in a significant increase in the levels of BNP, inflammatory factors (IL-1β, IL-6, TNF-α and CCL-2) in cardiac muscle cells, which exacerbates cardiomyocyte damage. Conversely, cholesterol excretion can cause significantly downregulation of BNP and inflammatory factors. Moreover, after knocking down Gramd1b, the accumulation of cholesterol in myocardial cells decreases, the levels of BNP and inflammatory factors significantly reduced, and the degree of myocardial cell damage was weakened. Knocking down Prkaca, inhibiting RhoA activity can all reverse cholesterol-induced elevation of BNP and inflammatory factors.

Conclusion: ASTER B-mediated intracellular accumulation of cholesterol in cardiac muscle cells may cause cardiomyocyte damage and inflammatory factor infiltration through PKA-Ca-RhoA pathways.
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http://dx.doi.org/10.1016/j.hjc.2021.06.003DOI Listing
June 2021

Comparative analysis of volatile and carotenoid metabolites and mineral elements in the flesh of 17 kiwifruit.

J Food Sci 2021 Jul 19;86(7):3023-3032. Epub 2021 Jun 19.

Key Laboratory of Horticultural Plant Biology (Ministry of Education), Huazhong Agricultural University, Wuhan, PR China.

Kiwifruit contains abundant nutritive compounds and is highly favored by the consumers worldwide. Therefore, detailed metabolic profiling is important to provide theoretic basis for the improvement of kiwifruit quality. In this study, the levels of volatiles, carotenoids, and mineral elements in the flesh of 17 kiwifruit accessions were evaluated. Acids and esters were the main volatiles in kiwifruit. During these 17 kiwifruit accessions, "Chenhong," three "Jinyan," and two "Guichang" germplasms were specifically rich in aromatic esters, which might be associated with their special taste. The main carotenoids were lutein, β-carotene, and zeaxanthin, and their levels were also genotype specific, with the green-fleshed "Guichang" having the highest level of carotenoids, and red-fleshed "Fuhong" and "Chenhong" being rich in zeaxanthin. Partial correlation analysis showed that the contents of some mineral elements were significantly correlated with those of specific volatiles and carotenoids, indicating the impacts of mineral elements on the accumulation of volatiles and carotenoids in the kiwifruit flesh. These results indicated that the contents of carotenoids and volatiles seemed to be affected by mineral elements and also provided a new potential method for improving fruit flavor quality in production.
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http://dx.doi.org/10.1111/1750-3841.15796DOI Listing
July 2021

Development and application of the Faba_bean_130K targeted next-generation sequencing SNP genotyping platform based on transcriptome sequencing.

Theor Appl Genet 2021 Jun 12. Epub 2021 Jun 12.

National Key Facility for Crop Gene Resources and Genetic Improvement, Institute of Crop Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100081, China.

Key Message: Large-scale faba bean transcriptome data are available, and the first genotyping platform based on liquid-phase probe targeted capture technology was developed for genetic and molecular breeding studies. Faba bean (Vicia faba L., 2n = 12) is an important food legume crop that is widely grown for multiple uses worldwide. However, no reference genome is currently available due to its very large genome size (approximately 13 Gb) and limited single nucleotide polymorphism (SNP) markers as well as highly efficient genotyping tools have been reported for faba bean. In this study, 16.7 billion clean reads were obtained from transcriptome libraries of flowers and leaves of 102 global faba bean accessions. A total of 243,120 unigenes were de novo assembled and functionally annotated. Moreover, a total of 1,579,411 SNPs were identified and further filtered according to a selection pipeline to develop a high-throughput, flexible, low-cost Faba_bean_130K targeted next-generation sequencing (TNGS) genotyping platform. A set of 69 Chinese faba bean accessions were genotyped with the TNGS genotyping platform, and the average mapping rate of captured reads to reference transcripts was 93.14%, of which 53.23% were located in the targeted regions. The TNGS genotyping results were validated by Sanger sequencing and the average consistency rate reached 93.6%. Comprehensive population genetic analysis was performed on the 69 Chinese faba bean accessions and identified four genetic subgroups correlated with the geographic distribution. This study provides valuable genomic resources and a reliable genotyping tool that could be implemented in genetic and molecular breeding studies to accelerate new cultivar development and improvement in faba bean.
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http://dx.doi.org/10.1007/s00122-021-03885-0DOI Listing
June 2021

Evaluation and optimization of radiomics features stability to respiratory motion in F-FDG 3D PET imaging.

Med Phys 2021 Jun 4. Epub 2021 Jun 4.

School of Biomedical Engineering and Guangdong Provincial Key Laboratory of Medical Image Processing, Southern Medical University, Guangzhou, China.

Purpose: To evaluate the impact of respiratory motion on radiomics features in F-fluoro-2-deoxy-D-glucose three dimensional positron emission tomography ( F-FDG 3D PET) imaging and optimize feature stability by combining preprocessing configurations and aggregation strategies.

Methods: An in-house developed respiratory motion phantom was imaged in 3D PET scanner under nine respiratory patterns including one reference pattern. In total, 487 radiomics features were extracted for each respiratory pattern. Feature stability to respiratory motion was first evaluated by metrics of coefficient of variation (COV) and relative difference (RD) in a fixed preprocessing configuration. Further, one-way ANOVA and trend analysis were performed to evaluate the impact of preprocessing configuration (voxel size, discretization scheme) and aggregation strategy on feature stability. Finally, an optimization framework was proposed by selected feature-specific configurations with minimum COV value, and the diagnostic performance was validated in stable versus unstable features and fixed versus optimal features by a set of 46 patients with lung disease.

Results: PET radiomics features were sensitive to respiratory motion, only 79/487 (16%) features were identified to be very stable in the fixed configuration. Preprocessing configuration and aggregation strategy had an impact on feature stability. For different voxel size, bin number, bin size and aggregation strategy, 188/487 (39%), 70/487 (15%), 148/487 (30%), and 38/95 (29%) features appeared significant changes in feature stability. The optimized configuration had the potential to improve feature stability compared to fixed configuration, with the COV decreased from 22% ±24% to 16% ±20%. Regarding the diagnostic performance, the stable and optimal configuration features outperformed the unstable and fixed configuration features, respectively (AUC 0.88, 0.87 vs. 0.83, 0.85).

Conclusions: Respiratory motion shows considerable impact on feature stability in 3D PET imaging, while optimizing preprocessing configuration may improve feature stability and diagnostic performance.
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http://dx.doi.org/10.1002/mp.15022DOI Listing
June 2021

An improved algorithm for the maximal information coefficient and its application.

R Soc Open Sci 2021 Feb 10;8(2):201424. Epub 2021 Feb 10.

Hunan Engineering and Technology Research Centre for Agricultural Big Data Analysis and Decision-making, Hunan Agricultural University, Changsha 410000, People's Republic of China.

The maximal information coefficient (MIC) captures both linear and nonlinear correlations between variable pairs. In this paper, we proposed the BackMIC algorithm for MIC estimation. The BackMIC algorithm adds a searching back process on the equipartitioned axis to obtain a better grid partition than the original implementation algorithm ApproxMaxMI. And similar to the ChiMIC algorithm, it terminates the grid search process by the -test instead of the maximum number of bins B(, ). Results on simulated data show that the BackMIC algorithm maintains the generality of MIC, and gives more reasonable grid partition and MIC values for independent and dependent variable pairs under comparable running times. Moreover, it is robust under different in B(, ). MIC calculated by the BackMIC algorithm reveals an improvement in statistical power and equitability. We applied (1-MIC) as the distance measurement in the K-means algorithm to perform a clustering of the cancer/normal samples. The results on four cancer datasets demonstrated that the MIC values calculated by the BackMIC algorithm can obtain better clustering results, indicating the correlations between samples measured by the BackMIC algorithm were more credible than those measured by other algorithms.
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http://dx.doi.org/10.1098/rsos.201424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074658PMC
February 2021

The prevalence of fatigue among Chinese nursing students in post-COVID-19 era.

PeerJ 2021 13;9:e11154. Epub 2021 Apr 13.

Centre for Cognitive and Brain Sciences, University of Macau, Macao, China.

Background: Due to the COVID-19 outbreak, all teaching activities in nursing schools were suspended in China, and many nursing students were summoned to work in hospitals to compensate for the shortage of manpower. This study examined the prevalence of fatigue and its association with quality of life (QOL) among nursing students during the post-COVID-19 era in China.

Methods: This was a multicenter, cross-sectional study. Nursing students in five Chinese universities were invited to participate. Fatigue, depressive and anxiety symptoms, pain and QOL were measured using standardized instruments.

Results: A total of 1,070 nursing students participated. The prevalence of fatigue was 67.3% (95% CI [64.4-70.0]). Multiple logistic regression analysis revealed that male gender ( = 0.003, OR = 1.73, 95% CI [1.20-2.49]), and being a senior nursing student (second year: OR = 2.20, 95% CI [1.46-3.33], < 0.001; third year: OR = 3.53, 95% CI [2.31-5.41], < 0.001; and fourth year OR = 3.59, 95% CI [2.39-5.40], < 0.001) were significantly associated with more severe fatigue. In addition, moderate economic loss during the COVID-19 pandemic (OR = 1.48, 95% CI [1.08-3.33], < 0.015; compared to low loss), participants with more severe depressive (OR = 1.48, 95% CI [1.22-1.78], < 0.001) and anxiety symptoms (OR = 1.12, 95% CI [1.05-1.20], = 0.001), and more severe pain (OR = 1.67, 95%CI [1.46-1.91], < 0.001) were significantly associated with reported more severe fatigue. After controlling for covariates, nursing students with fatigue had a lower overall QOL score compared to those without ( = 31.4, < 0.001).

Conclusion: Fatigue was common among nursing students in the post-COVID-19 era. Considering the negative impact of fatigue on QOL and daily functioning, routine physical and mental health screening should be conducted for nursing students. Effective stress-reduction measures should be enforced to assist this subpopulation to combat fatigue and restore optimal health.
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http://dx.doi.org/10.7717/peerj.11154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051357PMC
April 2021

Effects of Delayed Mating on the Reproductive Performance and Longevity of the Fall Armyworm, Spodoptera frugiperda (Lepidoptera: Noctuidae).

Neotrop Entomol 2021 May 3. Epub 2021 May 3.

Yangtze University, Jingzhou, Hubei Province, China.

The fall armyworm, Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae), a severe pest on agricultural crops occurring throughout the tropical Americas, has been reported to occur in China since 2019. To develop novel pest management practices, we studied the effect of delayed mating on the reproductive performance and longevity of S. frugiperda. Delayed mating, progressing from 0 to 7 days, was respectively imposed on both sexes simultaneously, female only, and male only. We demonstrated that delayed mating reduced mating success, number of eggs laid, egg hatch rate, and female oviposition period, while increased copulation duration and longevity. The correlations between the number of delayed days and mating success, number of eggs laid, hatch rate, and oviposition period were all significantly negative irrespective of the sex that was delayed. Meanwhile, there was a positive correlation between delayed days and copulation duration when both sexes were delayed simultaneously or males delayed only. Overall our results indicated that delayed mating in both males and females drastically reduced female reproductive output.
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http://dx.doi.org/10.1007/s13744-021-00877-zDOI Listing
May 2021

Changes in Nursing Students' Career Choices Following the COVID-19 Pandemic in China.

Front Psychiatry 2021 13;12:657021. Epub 2021 Apr 13.

Unit of Psychiatry, Department of Public Health and Medicinal Administration, Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macao, China.

Health professionals including nurses have experienced heavy workload and great physical and mental health challenges during the coronavirus disease 19 (COVID-19) pandemic, which may affect nursing students' career choices. This study examined the changes in nursing students' career choices after the onset of the COVID-19 pandemic in China. This study was conducted in five University nursing schools in China between September 14, 2020 and October 7, 2020. Career choices before and after the COVID-19 pandemic were collected and analyzed. In total, 1,070 nursing students participated in the study. The reported choice of nursing as future career increased from 50.9% [95% confidence interval (CI): 47.9-53.9%] before the COVID-19 pandemic to 62.7% (95%CI: 59.8-65.6%) after the onset of COVID-19 pandemic. Students who chose nursing as their future career following the COVID-19 outbreak had less severe depression and anxiety compared to those who did not choose nursing, but the associations of depression and anxiety with career choice disappeared in multivariable analyses. Binary logistic regression analysis revealed that male gender [odds ratio (OR) = 0.68, 95% CI: 0.50-0.91], rural residence (OR = 1.53, 95%CI: 1.17-2.00), fourth year students (OR = 0.50, 95%CI: 0.35-0.72), negative experiences during the COVID-19 pandemic (OR = 0.66, 95%CI: 0.47-0.92), and good health (OR = 4.6, 95%CI: 1.78-11.87) were significantly associated with the choice of nursing as future career after the onset of the COVID-19 pandemic. The COVID-19 pandemic appeared to have a positive influence on the career choice of nursing among Chinese nursing students.
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http://dx.doi.org/10.3389/fpsyt.2021.657021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076572PMC
April 2021

PAK5-mediated AIF phosphorylation inhibits its nuclear translocation and promotes breast cancer tumorigenesis.

Int J Biol Sci 2021 27;17(5):1315-1327. Epub 2021 Mar 27.

Department of Cell Biology, Key Laboratory of Cell Biology of National Health Commission of the PRC, Key Laboratory of Medical Cell Biology of Ministry of Education of the PRC, China Medical University, No.77, Puhe Road, Shenyang, 110122, Liaoning, China.

Although p21 activated kinase 5 (PAK5) is related to the progression of multiple cancers, its biological function in breast cancer remains unclear. Apoptosis-inducing factor (AIF) is a vital apoptosis factor in mitochondria, which can be released from mitochondria and enter the nucleus, causing caspase-independent apoptosis. In this study, we reveal that PAK5 inhibits apoptosis by preventing the nuclear translocation of AIF. PAK5 inhibits the release of AIF from mitochondria in breast cancer cells by decreasing the mitochondria membrane permeability and increasing the membrane potential. Furthermore, PAK5 phosphorylates AIF at Thr281 site to inhibit the formation of AIF/importin α3 complex, leading to decrease AIF nuclear translocation. Functionally, we demonstrate that PAK5-mediated AIF phosphorylation promotes the proliferation of breast cancer cells and accelerates the growth of breast cancer . Significantly, PAK5 and AIF expression in breast cancer are positively correlated with poor patient prognosis. PAK5 expression is negatively correlated with AIF nuclear translocation. These results suggest that PAK5-AIF signaling pathway may play an essential role in mammary tumorigenesis, providing a new therapeutic target for the treatment of breast cancer.
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http://dx.doi.org/10.7150/ijbs.58102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040471PMC
March 2021

Effect of income and energy efficiency on natural capital demand.

Environ Sci Pollut Res Int 2021 Apr 17. Epub 2021 Apr 17.

School of Economics, Ocean University of China, Qingdao, 266100, China.

This study explores the driving forces of natural capital demand to help solve the new problems faced by China's regional sustainable development and formulate relevant policies on resource utilization, ecological compensation, and energy structural adjustment. We find a significant and inverted U-shaped relationship between income and natural capital demand. Both economic development and environmental protection can only be improved beyond the inflection point. Energy efficiency is also closely related to natural capital demand, and its continuous improvement can slow down the rise in natural capital demand. This research provides important implications for the spread and allocation of natural capital regionally. It recommends the national allocation of natural capital, formulation of differentiated environmental policies, and improvement in energy efficiency by improving scale, technology, and structure.
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http://dx.doi.org/10.1007/s11356-021-13971-xDOI Listing
April 2021

Circular RNA circ-PTEN elevates PTEN inhibiting the proliferation of non-small cell lung cancer cells.

Hum Cell 2021 Jul 5;34(4):1174-1184. Epub 2021 Apr 5.

Department of Thoracic Surgery, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, Liaoning, 110004, PR China.

Phosphatase and tensin homolog (PTEN) is a well-known tumor suppressor in various cancer types, including non-small cell lung cancer (NSCLC). Circular RNA (circRNA) has recently been proven to be strongly linked with cancer progression. Here, we aimed to investigate the biological relevance and clinical significance of circRNA derived from PTEN in NSCLC. We found that circ-PTEN (hsa_circ_0094342) was significantly decreased in NSCLC tissues and serum, which was attributed to the upregulation of RNA-binding protein DHX9. Low circ-PTEN was linked with malignant clinical features and poor outcome. Exogenous expression of circ-PTEN markedly inhibited NSCLC cell proliferation in vitro as well as retarded tumor growth in vivo. Circ-PTEN increased the expression of its host gene PTEN via acting as a sponge for miR-155 and miR-330-3p, leading to the inactivation of the carcinogenic PI3K/AKT signaling pathway. The xenograft tumor model also indicated the existence of circ-PTEN/miR-155/miR-330-3p/PTEN regulatory axis in vivo. Our data for the first time demonstrate that circ-PTEN functions as a tumor-inhibiting circRNA in NSCLC through post-transcriptionally regulating PTEN, hinting a promising diagnostic/prognostic biomarker as well as therapeutic target for NSCLC patients.
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http://dx.doi.org/10.1007/s13577-021-00526-yDOI Listing
July 2021

Comparative profiling and natural variation of polymethoxylated flavones in various citrus germplasms.

Food Chem 2021 Aug 8;354:129499. Epub 2021 Mar 8.

Key Laboratory of Horticultural Plant Biology (Ministry of Education), College of Horticulture and Forestry, Huazhong Agricultural University, Wuhan 430070, PR China. Electronic address:

Citrus fruits are the main dietary source of polymethoxylated flavones (PMFs) with significant effects on consumer health. In this study, eleven main PMFs were evaluated in the fruit flavedo or leaves of 116 citrus accessions via UPLC-DAD-ESI-QTOF-MS/MS combined with HPLC-DAD analysis, which revealed significant species-specific and spatiotemporal characteristics. All Citrus reticulata and their natural or artificial hybrids were found to have detectable PMFs, especially in the fruit flavedo of the wild or early-cultivated mandarins at early fruit development stages. However, PMFs were not detected in citrons, pummelos, kumquats, trifoliata oranges, papedas, Chinese box oranges and 'Mangshanyegan'. The results enlightened that PMF accumulation only in mandarins and mandarin hybrids is a phenotype inherited from mandarin ancestors. This study provides a comprehensive PMF profile in various citrus germplasms and will benefit future functional citrus breeding practices aimed at designing plants rich in total or specific PMFs for health benefits.
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http://dx.doi.org/10.1016/j.foodchem.2021.129499DOI Listing
August 2021

CRISPR/Cas9-Mediated Gene Editing Revolutionizes the Improvement of Horticulture Food Crops.

J Agric Food Chem 2021 Mar 18. Epub 2021 Mar 18.

College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, People's Republic of China.

Horticultural food crops are important sources of nutrients for humans. With the increase of the global population, enhanced horticulture food crop production has become a new challenge, and enriching their nutritional content has also been required. Gene editing systems, such as zinc finger nucleases, transcription activator-like effector nucleases, and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9), have accelerated crop improvement through the modification of targeted genomes precisely. Here, we review the development of various gene editors and compare their advantages and shortcomings, especially the newly emerging CRISPR/Cas systems, such as base editing and prime editing. We also summarize their practical applications in crop trait improvement, including yield, nutritional quality, and other consumer traits.
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http://dx.doi.org/10.1021/acs.jafc.1c00104DOI Listing
March 2021

Potential role of glucosamine-phosphate N-acetyltransferase 1 in the development of lung adenocarcinoma.

Aging (Albany NY) 2021 03 3;13(5):7430-7453. Epub 2021 Mar 3.

Department of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, Heilongjiang, People's Republic of China.

Glucosamine-phosphate N-acetyltransferase 1 (GNPNAT1) is a key enzyme associated with glucose metabolism and uridine diphosphate-N-acetylglucosamine biosynthesis. Abnormal expression might be associated with carcinogenesis. We analyzed multiple lung adenocarcinoma (LUAD) gene expression databases and verified higher expression in LUAD tumor tissues than in normal tissues. Moreover, we analyzed the survival relationship between LUAD patients' clinical status and expression, and found higher expression in LUAD patients with unfavorable prognosis. We built gene co-expression networks and further annotated the co-expressed genes' Gene Ontology (GO) terms, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and various associated regulatory factors. These co-expression genes' functional networks mainly participate in chromosome segregation, RNA metabolic process, and RNA transport. We analyzed genetic alterations and co-occurrence networks, and the functional networks of these genes showed that participates in multiple steps of cell cycle transition and in the development of some cancers. We assessed the correlation between expression and cancer immune infiltrates and showed that expression is correlated with several immune cells, chemokines, and immunomodulators in LUAD. We found that correlates with LUAD development and prognosis, laying a foundation for further research, especially in immunotherapy.
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http://dx.doi.org/10.18632/aging.202604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993716PMC
March 2021

Investigation of the Impact of Polymorphism on Drug-Drug Interaction between Tacrolimus and Schisantherin A/Schisandrin A Based on Physiologically-Based Pharmacokinetic Modeling.

Pharmaceuticals (Basel) 2021 Feb 27;14(3). Epub 2021 Feb 27.

Department of Clinical Pharmacy and Pharmacy Administration, College of Pharmacy, Fudan University, Shanghai 201203, China.

Wuzhi capsule (WZC) is commonly prescribed with tacrolimus in China to ease drug-induced hepatotoxicity. Two abundant active ingredients, schisantherin A (STA) and schisandrin A (SIA) are known to inhibit CYP3A enzymes and increase tacrolimus's exposure. Our previous study has quantitatively demonstrated the contribution of STA and SIA to tacrolimus pharmacokinetics based on physiologically-based pharmacokinetic (PBPK) modeling. In the current work, we performed reversible inhibition (RI) and time-dependent inhibition (TDI) assays with genotyped human liver microsomes (HLMs), and further integrated the acquired parameters into the PBPK model to predict the drug-drug interaction (DDI) in patients with different alleles. The results indicated STA was a time-dependent and reversible inhibitor of CYP3A4 while only a reversible inhibitor of CYP3A5; SIA inhibited CYP3A4 and 3A5 in a time-dependent manner but also reversibly inhibited CYP3A5. The predicted fold-increases of tacrolimus exposure were 2.70 and 2.41, respectively, after the multidose simulations of STA. SIA also increased tacrolimus's exposure but to a smaller extent compared to STA. An optimized physiologically-based pharmacokinetic (PBPK) model integrated with polymorphism was successfully established, providing more insights regarding the long-term DDI between tacrolimus and Wuzhi capsules in patients with different genotypes.
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http://dx.doi.org/10.3390/ph14030198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997453PMC
February 2021

High mobility group box 1 promotes the differentiation of spinal ependymal cells into astrocytes rather than neurons.

Neuroreport 2021 03;32(5):399-406

Department of Neurosurgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.

Spinal ependymal cells are involved in proliferation, differentiation and migration after spinal cord injury (SCI) and represent an endogenous source of repair cells for treating SCI. However, 95% of activated ependymal cells eventually differentiate into astrocytes after SCI and ultimately contribute more than half of the new astrocytes that form glial scars in vivo. The factors that regulate the fate of ependymal cells after SCI remain unclear. High mobility group box 1 (HMGB1) is regarded as an important proinflammatory factor in nerve injury, and recent studies have shown that HMGB1 can regulate the fate of stem cells after injury. In this study, we investigated whether HMGB1 released from reactive astrocytes after SCI regulates the proliferation and differentiation of ependymal cells in vitro. Ependymal cells extracted and cultured from the spinal cord of mice were separately treated with astrocyte culture medium (ACM), IL-1β, ACM (IL-1β) and the HMGB1 protein, and the proliferation and differentiation of ependymal cells were detected. Additionally, an HMGB1-neutralizing antibody (anti-HMGB1) was added to further verify the regulatory effect of HMGB1 on ependymal cells. The results showed that HMGB1 released from reactive astrocytes promoted ependymal cell differentiation into astrocytes and inhibited ependymal cell differentiation into neurons in vitro; however, the effect disappeared after the addition of anti-HMGB1. HMGB1 had no significant effect on ependymal cell proliferation. Our findings demonstrate that HMGB1 can regulate the differentiation of ependymal cells after SCI. These results provide a new strategy for the treatment of SCI.
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http://dx.doi.org/10.1097/WNR.0000000000001609DOI Listing
March 2021

Treatment of symptomatic Chiari I malformation by "all-factors-surgery": a report of 194 cases.

Eur Spine J 2021 Jun 22;30(6):1615-1622. Epub 2021 Feb 22.

Department of Neurosurgery and Key Laboratory of Neurotrauma, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China.

Purpose: Inadequate decompressions can lead to poor improvement of symptoms in patients with Chiari I malformation (CMI). In this study, the "all-factors-surgery" that including all levels decompressions was performed on symptomatic CMI patients for the snake of eliminating all possible pathogenic factors and reducing the chance of reoperation.

Methods: The "all-factors-surgery" combined operations of posterior fossa decompression, enlarged cranioplasty, duraplasty, cerebellar tonsil partial resection and adhesion release. Total 194 patients from January 2010 to December 2015. The outcome measures included improvement rate of symptoms, patients self-evaluation (improved, unchanged, worsened), Visual Analogue Scale (VAS) score, Japanese Orthopaedic Association (JOA) score, Chicago Chiari Outcome Scale (CCOS) score, the diameter of the syrinx and complications.

Results: Postoperative data were collected from the three stages: at discharge, the short-term follow-up (average, 9.39 months), and the long-term follow-up (average, 54.44 months). Patients self-evaluation improvement rate in the three follow-up stages was 92.27%, 90.07% and 85.93%. The VAS scores (mean, 1.49, 1.21, 1.47 vs 3.76) and JOA scores (mean, 15.66, 15.99, 16.10 vs 14.84) were significant difference between the follow-up and pre-operation (P < .05). The CCOS scores of short-term and long-term follow-up were significantly better than that at discharge (mean, 14.75, 14.87 vs 13.68) (P < .05). The diameter of syrinx in each follow-up stage was significantly less than that in pre-operation (mean, 3.39, 1.95, 1.87 vs 5.09) (P < .05). There were no serious complications, and no one asked for reoperation during the follow up.

Conclusion: Symptomatic CMI patients undergoing "all-factors-surgery" had persistently high rates of symptom relief and rarely needed reoperation.
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http://dx.doi.org/10.1007/s00586-021-06720-8DOI Listing
June 2021

Antibody-Mediated Delivery of Chimeric BRD4 Degraders. Part 2: Improvement of In Vitro Antiproliferation Activity and In Vivo Antitumor Efficacy.

J Med Chem 2021 03 17;64(5):2576-2607. Epub 2021 Feb 17.

WuXi AppTec, 288 Fute Zhong Road, Waigaoqiao Free Trade Zone, Shanghai 200131, China.

Heterobifunctional compounds that direct the ubiquitination of intracellular proteins in a targeted manner via co-opted ubiquitin ligases have enormous potential to transform the field of medicinal chemistry. These chimeric molecules, often termed proteolysis-targeting chimeras (PROTACs) in the chemical literature, enable the controlled degradation of specific proteins via their direction to the cellular proteasome. In this report, we describe the second phase of our research focused on exploring antibody-drug conjugates (ADCs), which incorporate BRD4-targeting chimeric degrader entities. We employ a new BRD4-binding fragment in the construction of the chimeric ADC payloads that is significantly more potent than the corresponding entity utilized in our initial studies. The resulting BRD4-degrader antibody conjugates exhibit potent and antigen-dependent BRD4 degradation and antiproliferation activities in cell-based experiments. Multiple ADCs bearing chimeric BRD4-degrader payloads also exhibit strong, antigen-dependent antitumor efficacy in mouse xenograft assessments that employ several different tumor models.
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http://dx.doi.org/10.1021/acs.jmedchem.0c01846DOI Listing
March 2021

Antibody-Mediated Delivery of Chimeric BRD4 Degraders. Part 1: Exploration of Antibody Linker, Payload Loading, and Payload Molecular Properties.

J Med Chem 2021 03 17;64(5):2534-2575. Epub 2021 Feb 17.

Genentech Inc., 1 DNA Way, South San Francisco, California 94080, United States.

The biological and medicinal impacts of proteolysis-targeting chimeras (PROTACs) and related chimeric molecules that effect intracellular degradation of target proteins via ubiquitin ligase-mediated ubiquitination continue to grow. However, these chimeric entities are relatively large compounds that often possess molecular characteristics, which may compromise oral bioavailability, solubility, and/or in vivo pharmacokinetic properties. We therefore explored the conjugation of such molecules to monoclonal antibodies using technologies originally developed for cytotoxic payloads so as to provide alternate delivery options for these novel agents. In this report, we describe the first phase of our systematic development of antibody-drug conjugates (ADCs) derived from bromodomain-containing protein 4 (BRD4)-targeting chimeric degrader entities. We demonstrate the antigen-dependent delivery of the degrader payloads to PC3-S1 prostate cancer cells along with related impacts on MYC transcription and intracellular BRD4 levels. These experiments culminate with the identification of one degrader conjugate, which exhibits antigen-dependent antiproliferation effects in LNCaP prostate cancer cells.
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http://dx.doi.org/10.1021/acs.jmedchem.0c01845DOI Listing
March 2021

Dynamics and risk assessment of pesticides in cucumber through field experiments and model simulation.

Sci Total Environ 2021 Jun 4;773:145615. Epub 2021 Feb 4.

Innovation Center of Pesticide Research, Department of Applied Chemistry, College of Science, China Agricultural University, Beijing 100193, PR China. Electronic address:

Pesticides are often applied multiple times during cucumber cultivation in China. In order to obtain the residue concentrations and subsequently human health risk assessment after pesticide multiple applications, plenty of field trials have been conducted, consuming a lot of labor force and funds. The application of kinetic models can address this problem to some extent by predicting the residue values of pesticides in cucumber. In this study, a dynamic model (dynamiCROP) was applied in combination with field experiments to investigate the distribution, translocation, and dissipation after the one-time application of seven pesticides in a cucumber-soil environment. Moreover, the residue concentrations after the second and third applications of the seven pesticides were estimated through a "simple superposition method", i.e., superimposing the output results of dynamiCROP after each single pesticide application. The estimated residue concentrations show good agreement with that measured through field experiments with R = 0.865 and relative root mean squared error (RRMSE) = 13.2%. Meanwhile, the short- and long-term risks of each pesticide were assessed according to the concentrations estimated by the "simple superposition method" with the dynamiCROP model. It shows that the seven pesticides, applied multiple times during cucumber cultivation, pose a very low dietary risk to human health through cucumber intake. Our study presents a cost- and time-efficient way to investigate the dissipation of pesticides in the cucumber-soil environment, predicate the residue concentrations of pesticides after multiple applications and assess the dietary risk of pesticides to human health through cucumber intake.
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http://dx.doi.org/10.1016/j.scitotenv.2021.145615DOI Listing
June 2021
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