Publications by authors named "Lina Zhao"

370 Publications

Histidine protonation states are key in the LigI catalytic reaction mechanism.

Proteins 2021 Jul 27. Epub 2021 Jul 27.

Department of Clinical Sciences, Lund University, Box 50332, SE-202 13, Malmö, Sweden.

Lignin is one of the world's most abundant organic polymers, and 2-pyrone-4,6-dicarboxylate lactonase (LigI) catalyzes the hydrolysis of 2-pyrone-4,6-dicarboxylate (PDC) in the degradation of lignin. The pH has profound effects on enzyme catalysis and therefore we studied this in the context of LigI. We found that changes of the pH mostly affects surface residues, while the residues at the active site are more subject to changes of the surrounding microenvironment. In accordance with this, a high pH facilitates the deprotonation of the substrate. Detailed free energy calculations by the empirical valence bond (EVB) approach revealed that the overall hydrolysis reaction is more likely when the three active site histidines (His31, His33 and His180) are protonated at the &ip.eop; site, however, protonation at the δ site may be favored during specific steps of the reaction. Our studies have uncovered the determinant role of the protonation state of the active site residues His31, His33 and His180 in the hydrolysis of PDC. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/prot.26191DOI Listing
July 2021

Physicochemical Characterization and Biopharmaceutical Evaluation of ZWF: A Novel Anticancer Drug for the Treatment of Non-small Cell Lung Cancer.

AAPS PharmSciTech 2021 Jul 23;22(6):207. Epub 2021 Jul 23.

Key Laboratory of Drug-Targeting and Drug Delivery Systems of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, People's Republic of China.

The orally available novel small molecule drug ZWF is under preclinical development for an anticancer purpose. The present study aimed to assess the viability of developing ZWF as a form of oral formulation for clinical application based on the principles of biopharmaceutics and pharmacokinetics. The crucial physicochemical properties of ZWF were determined by in vitro assays. The in situ gastrointestinal absorption characteristics and in vivo pharmacokinetic behaviors of ZWF in rats were characterized. The solubility of ZWF showed a highly pH-dependent profile, decreasing from 25,392.89 to 20.48 μg/mL as the solution pH increased from 1.0 to 5.8. In PBS with a pH of 1.0 to 5.8, the LogP value of ZWF ranged from -2.35 to 2.20 and was gradually increased as the pH value increased. ZWF was partially absorbed in the stomach, and the favorable absorption sites were the duodenum, jejunum, and ileum. Pharmacokinetic studies showed that the AUC and C values of ZWF after its oral administration as a suspension prepared with 0.5% CMC-Na were increased by 18.97% and 40% than that with normal saline, providing a model oral formulation of ZWF with ideal bioavailability and system exposure in rats. From the perspective of oral absorption, ZWF possessed appealing qualities as a drug candidate and could be prepared as an oral preparation for clinical application. The present study has established a fundamental foundation for the development and quality evaluation of the ZWF oral formulations.
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http://dx.doi.org/10.1208/s12249-021-02084-wDOI Listing
July 2021

AURKB, CHEK1 and NEK2 as the Potential Target Proteins of on Hepatocellular Carcinoma: An Integrated Bioinformatics Analysis.

Int J Gen Med 2021 12;14:3295-3312. Epub 2021 Jul 12.

Department of gastroenterology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China.

Objective: We aim to explore the potential anti-HCC mechanism of through integrated bioinformatics analysis.

Methods: We searched active ingredients and related targets of via TCMSP database, PubChem and SwissTargetPrediction database. Then, we identified HCC disease targets from GEO dataset by WGCNA. Next, the intersected targets of disease targets and drug targets were input into STRING database to construct PPI networking in order to obtain potential therapeutic targets of . Cytoscape software was used to carry out network topology analysis of potential targets. We used the R package for GO analysis and KEGG analysis. Finally, we used AutoDock vina and PyMOL software for molecular docking.

Results: Sixteen active components from were lastly selected for further investigation. A total of 442 component targets were identified from 16 active ingredients of after the removal of duplicate targets. GSE45436 was selected for construction of WGCNA and screening of differentially expressed genes. A total of 354 genes were up-regulated in HCC samples and 100 were down-regulated in HCC patients. Twenty-one common genes were obtained by intersection and 10 critical targets were filtered for further investigation. The enrichment analysis showed that cell cycle, DNA replication, p53 signaling pathway were mainly involved. The molecular docking results showed that 4 potential combinations were with the best binding energy and molecular interactions.

Conclusion: AURKB, CHEK1 and NEK2 could be the potential target proteins of in treating HCC. Cell cycle, DNA replication, p53 signaling pathway consist of the fundamental regulation cores in this mechanism.
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http://dx.doi.org/10.2147/IJGM.S318077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285231PMC
July 2021

Expression of Autophagy-Related Factors LC3A and Beclin 1 and Apoptosis-Related Factors Bcl-2 and BAX in Osteoblasts Treated With Sodium Fluoride.

Front Physiol 2021 1;12:603848. Epub 2021 Jul 1.

Department of Pathology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China.

Objective: This study aims to analyze the expressions of autophagy-related factors light chain 3 alpha (LC3A) and Beclin 1 and apoptosis-related factors B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X (BAX) in primary osteoblasts treated with sodium fluoride (NaF).

Methods: Osteoblasts were extracted from Sprague-Dawley rats and treated with 0, 2.5, 5, and 10 mg/L NaF solutions, followed by 10 mmol/L 3-methyladenine (3-MA) for 24 h. The apoptotic rate was determined by flow cytometry, and the expressions of the autophagy- and apoptosis-related factors were measured by western blotting and real-time quantitative polymerase chain reaction.

Results: The mRNA expressions of LC3A, Beclin 1, and BAX in the NaF-treated osteoblast group were higher than those in the control group, while the protein expressions of these factors in the NaF-treated group were significantly higher than those in the control group. However, the Bcl-2 protein expression in the NaF-treated osteoblasts was significantly decreased compared to that in the control cells. After the 3-MA treatment, the protein expressions of LC3A, Beclin 1, and Bcl-2 were significantly decreased compared with those of the NaF-treated group, whereas the expression of BAX increased. Moreover, the apoptosis rate was increased after the addition of the 3-MA inhibitor.

Conclusion: NaF stimulation promoted autophagy and apoptosis of the osteoblasts, suggesting the involvement of fluoride damage in these processes.
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http://dx.doi.org/10.3389/fphys.2021.603848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281676PMC
July 2021

The Underlying Function and Structural Organization of the Intracellular Protein Corona on Graphdiyne Oxide Nanosheet for Local Immunomodulation.

Nano Lett 2021 07 9;21(14):6005-6013. Epub 2021 Jul 9.

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, China.

Nanomaterial-biology interaction is the critical step in the fate of biomedical nanomedicines, influencing the consequent biological outcomes. Herein, we present two-dimensional carbon-based nanomaterials-graphdiyne oxide (GDYO) nanosheets that interact with an intracellular protein corona consisting of signal transducer and activator of transcription 3 (STAT3), inducing the reeducation of immunosuppressive macrophages. The interaction at the GDYO-STAT3 interface, driven by structure matching, hydrogen bonding, and salt bridges, simultaneously triggers the immune response in the tumor microenvironment, facilitating cancer immunotherapy. For the first time, our data reveal an interaction mechanism between the nanoparticle-protein interfaces inevitably formed inside the cells that determines the macrophage phenotype. Our results suggest that GDYO nanosheets could be applied for local immunomodulation due to their function and structural organization of the intracellular protein corona occurred inside macrophages.
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http://dx.doi.org/10.1021/acs.nanolett.1c01048DOI Listing
July 2021

Unravelling the fruit microbiome: The key for developing effective biological control strategies for postharvest diseases.

Compr Rev Food Sci Food Saf 2021 Jun 30. Epub 2021 Jun 30.

Department of Postharvest Science, ARO, the Volcani Center, Rishon LeZion, Israel.

Fruit-based diets are recognized for their benefits to human health. The safety of fruit is a global concern for scientists. Fruit microbiome represents the whole microorganisms that are associated with a fruit. These microbes are either found on the surfaces (epiphytes) or in the tissues of the fruit (endophytes). The recent knowledge gained from these microbial communities is considered relevant to the field of biological control in prevention of postharvest fruit pathology. In this study, the importance of the microbiome of certain fruits and how it holds promise for solving the problems inherent in biocontrol and postharvest crop protection are summarized. Research needs on the fruit microbiome are highlighted. Data from DNA sequencing and "meta-omics" technologies very recently applied to the study of microbial communities of fruits in the postharvest context are also discussed. Various fruit parameters, management practices, and environmental conditions are the main determinants of the microbiome. Microbial communities can be classified according to their structure and function in fruit tissues. A critical mechanism of microbial biological control agents is to reshape and interact with the microbiome of the fruit. The ability to control the microbiome of any fruit is a great potential in postharvest management of fruits. Research on the fruit microbiome offers important opportunities to develop postharvest biocontrol strategies and products, as well as the health profile of the fruit.
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http://dx.doi.org/10.1111/1541-4337.12783DOI Listing
June 2021

CREB1 and ATF1 Negatively Regulate Glutathione Biosynthesis Sensitizing Cells to Oxidative Stress.

Front Cell Dev Biol 2021 10;9:698264. Epub 2021 Jun 10.

School of Life Sciences, Tsinghua University, Beijing, China.

The cAMP response element binding protein (CREB) family activating transcription factor 1 (ATF1) and cAMP response element binding protein 1 (CREB1) have been reported in a diverse group of tumors, however, the mechanistic basis for this remains unclear. Here we found that CREB1 and ATF1 unexpectedly regulate glutathione (GSH) biosynthesis by suppressing the expression of glutamate-cysteine ligase modifier subunit (GCLM) and glutathione synthase (GSS), two key enzymes of GSH biosynthesis pathway. Mechanistic studies reveal that GCLM and GSS are direct transcriptional targets of CREB1 and ATF1. Through repressing the expression of these two enzymes, CREB1 and ATF1 reduce the GSH biosynthesis and the capability of cells to detoxicate reactive oxygen species (ROS), thereby increasing cellular susceptibility to oxidative stress. Therefore, our findings link CREB1 family to cellular metabolism, and uncover a potential therapeutic approach by targeting GCLM or oxidative stress for the treatment of tumors with relatively high expression of CREB1 family proteins.
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http://dx.doi.org/10.3389/fcell.2021.698264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223876PMC
June 2021

Detailed analysis of recovery process of cranial nerve palsy after IMRT-based comprehensive treatment in nasopharyngeal carcinoma.

Radiat Oncol 2021 Jun 27;16(1):118. Epub 2021 Jun 27.

Department of Radiation Oncology, Xijing Hospital, Fourth Military Medical University, No. 127, Chang Le West Road, Xi'an, 710032, China.

Background: Cranial nerve (CN) palsy due to cancer involvement has been considered as an unfavorable prognostic factor for patients with nasopharyngeal carcinoma (NPC). We assessed the role of IMRT based treatment on the recovery of CN palsy and investigated the prognostic value of complete recovery of CN palsy.

Methods: A total of 115 NPC patients with cancer-related CN palsy were included in the study. We referred CTCAE version 5.0 to evaluate the grade of CN palsy.

Results: All patients with grade 1 CN palsy recovered completely during the 2 years of follow-up after definite treatment. Most grade 2 palsy could change gradually to grade 1 palsy or complete recovery during 2 years of follow-up. Patients with more than 2 symptoms of CN palsy had poor 3-year disease-free survival (DFS) than these with 1 or 2 symptoms (60.3% vs. 84.9%, HR 0.25, 95% CI 0.07-0.89, P = 0.001). There were no significant differences for PFS, OS, DMFS and LRFS between patients with complete recovery and non-complete recovery from CN palsy after receiving IMRT based comprehensive treatment.

Conclusions: IMRT based comprehensive treatment could effectively promote the recovery of tumor-related CN palsy for NPC patient. More than 2 symptoms of CN palsy was a poor prognostic factor for DFS of NPC patients. The prognostic role of complete recovery of CN palsy was not identified in our study.
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http://dx.doi.org/10.1186/s13014-021-01846-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237430PMC
June 2021

Artesunate attenuates proliferation of epithelial cells by downregulating the NF-κB and AKT signaling pathways in benign mammary gland hyperplasia rats.

Ann Transl Med 2021 May;9(10):848

Department of Breast, Dongfang Hospital Beijing University of Chinese Medicine, Beijing, China.

Background: The aim of this study was to investigate the effects of artesunate (ART) on breast epithelial cell proliferation and .

Methods: Immortalized human non-cancer mammary epithelial (MCF-10A) cells were used to determine the effect of ART on estrogen-induced mammary hyperplasia cells. We investigated the effect of ART on the synthesis of cyclooxygenase-2 (COX-2) and proliferating cell nuclear antigen (PCNA) in MCF-10A by treating MCF-10A 36 h with different concentrations of ART (0, 100, 200, 400 µm, n=12/group). We then investigated the effect of ART on estrogen induced COX-2, PCNA, nuclear factor-kappa B (NF-κB), and pNF-κB synthesis by treating MCF-10A with both estrogen and ART (0, 50, 100, 200 µm, n=12/group). A mammary hyperplasia model (MGH) was established in rats. All rats (n=12) were divided into 4 groups [group A: negative control (NC) + Art -; group B: NC + Art +; group C: MGH + Art -; group D: MGH + Art +] by the random number table method and the effects of ART on estradiol-induced mammary hyperplasia, fibrosis, and phosphorylation of AKT and NF-κB were studied by histopathological staining, Masson trichrome staining, immunohistochemistry (IHC), and western blotting.

Results: The proliferation and inflammation of mammary epithelial cells were blocked by ART (P<0.05). The phosphorylation of NF-κB induced by estradiol in MCF-10A was attenuated by ART (P<0.05). In the rat MGH, ART reduced cell proliferation and fibrosis (P<0.05) and inhibited the phosphorylation of AKT and NF-κB (P<0.05).

Conclusions: The drug ART inhibits estrogen-induced breast hyperplasia by blocking AKT and NFkB phosphorylation.
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http://dx.doi.org/10.21037/atm-21-1447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184455PMC
May 2021

Prognostic analysis of 152 patients with distant metastasis after intensity-modulated radiotherapy for nasopharyngeal carcinoma.

Ann Palliat Med 2021 Jun 16;10(6):6824-6832. Epub 2021 Jun 16.

Department of Radiation Oncology, First Affiliated Hospital of Air Force Medical University, Xi'an, China.

Background: The aim of this study was to analyze the prognostic factors for nasopharyngeal carcinoma (NPC) patients with distant metastasis after intensity-modulated radiotherapy (IMRT), and to provide a further basis for clinical treatment options.

Methods: One hundred and fifty-two NPC patients with distant metastasis after IMRT from January 2006 to December 2017 were included in this study and reviewed for analysis. The patients were followed up for a median time of 43 months. The survival rate was calculated and compared using the Kaplan-Meier method and log-rank tests, respectively. The Cox risk ratio model was used for univariate and multivariate analyses.

Results: Among all patients, the median interval from treatment completion to distant metastasis was 11.3 months. The median post-metastasis survival was 14 months, and the 1-, 2-, and 3-year survival rates were 60.4%, 40.2%, and 27.6%, respectively. Through univariate analysis, we found that overall survival was related to lymph node (N) staging at diagnosis, whether induction chemotherapy was utilized, the interval time from initial radiotherapy completion to distant metastasis, with/without liver metastasis, and whether chemotherapy or palliative radiotherapy were utilized after metastasis discovery. Cox regression results showed that liver metastasis, multi-organ metastasis, chemotherapy after metastasis, and the time from radiotherapy completion to distant metastasis were independent prognostic factors for patient survival.

Conclusions: The prognosis of NPC patients with distant metastasis after IMRT was related to the time from radiotherapy completion to distant metastasis, liver and multi-organ metastasis, and whether adjuvant chemotherapy was administered. Both adequate adjuvant chemotherapy and palliative radiotherapy could potentially prolong the patients' survival.
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http://dx.doi.org/10.21037/apm-21-1279DOI Listing
June 2021

Ultimate conversion efficiency of second harmonic generation in all-dielectric resonators of quasi-BICs in consideration of nonlinear refraction of dielectrics.

Opt Express 2021 May;29(11):17286-17294

We investigate second harmonic generation (SHG) in all-dielectric resonance nanostructures of high-Q factors assisted by quasi-bound states in the continuum (quasi-BICs). The typical resonators, e.g., guided-mode resonance gratings and asymmetric metasurfaces, fabricated by AlGaAs were numerically studied with the consideration of nonlinear refraction of AlGaAs. The resonance peak and line-shape of linear transmission and SHG spectra in the resonators can be dramatically changed under intense pump intensities. The SHG conversion efficiency in the nanostructures working at quasi-BICs is much lower than the traditionally expected values without considering the nonlinear refraction of dielectrics. The ultimate SHG conversion efficiency is finally obtained. The investigation has the significance for the design and understanding of efficient nonlinear metasurfaces of high-Q factors.
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http://dx.doi.org/10.1364/OE.427355DOI Listing
May 2021

Hydrophobic-modified metal-hydroxide nanoflocculants enable one-step removal of multi-contaminants for drinking water production.

iScience 2021 May 30;24(5):102491. Epub 2021 Apr 30.

Department of Civil and Environmental Engineering, Imperial College London, London, SW7 2AZ, UK.

Flocculation is a mainstream technology for the provision of safe drinking water but is limited due to the ineffectiveness of conventional flocculants in removing trace low-molecular-weight emerging contaminants. We described a synthesis strategy for the development of high-performance nanoflocculants (hydrophobic-organic-chain-modified metal hydroxides [HOC-M]), imitating surfactant-assembling nano-micelles, by integration of long hydrophobic chains with traditional inorganic metal (Fe/Al/Ti)-based flocculants. The core-shell nanostructure was highly stable in acidic stock solution and transformed to meso-scale coagulation nuclei in real surface water. In both jar and continuous-flow tests, HOC-M was superior over conventional flocculants in removing many contaminants (turbidity, UV, and DOC: >95%; TP and NO-N: >90%; trace pharmaceuticals [initial concentration: 100 ng/L]: >80%), producing flocs with better structural and dewatering properties, and lowering the environmental risk of metal leaching. The rationally designed nanoflocculants have large application potential, as a solution to increasing public concern about micro-pollutants and increasing water quality requirements.
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http://dx.doi.org/10.1016/j.isci.2021.102491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169996PMC
May 2021

Identifying Dendritic Cell-Related Genes Through a Co-Expression Network to Construct a 12-Gene Risk-Scoring Model for Predicting Hepatocellular Carcinoma Prognosis.

Front Mol Biosci 2021 24;8:636991. Epub 2021 May 24.

Department of Gastroenterology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.

The prognostic prediction of hepatocellular carcinoma (HCC) is still challenging. Immune cells play a crucial role in tumor initiation, progression, and drug resistance. However, prognostic value of immune-related genes in HCC remains to be further clarified. In this study, the mRNA expression profiles and corresponding clinical information of HCC patients were downloaded from public databases. Then, we estimated the abundance of immune cells and identified the differentially infiltrated and prognostic immune cells. The weighted gene co-expression network analysis (WGCNA) was performed to identify immune-related genes in TCGA cohort and GEO cohort. The least absolute shrinkage and selection operator (LASSO) Cox regression model was applied to establish a risk-scoring model in the TCGA cohort. HCC patients from the GSE14520 datasets were utilized for risk model validation. Our results found that high level of dendritic cell (DC) infiltration was associated with poor prognosis. Over half of the DC-related genes (58.2%) were robustly differentially expressed between HCC and normal specimens in the TCGA cohort. 17 differentially expressed genes (DEGs) were found to be significantly associated with overall survival (OS) by univariate Cox regression analysis. A 12-gene risk-scoring model was established to evaluate the prognosis of HCC. The high-risk group exhibits significantly lower OS rate of HCC patients than the low-risk group. The risk-scoring model shows benign predictive capacity in both GEO dataset and TCGA dataset. The 12-gene risk-scoring model may independently perform prognostic value for HCC patients. Receiver operating characteristic (ROC) curve analysis of the risk-scoring model in GEO cohort and TCGA cohort performed well in predicting OS. Taken together, the 12-gene risk-scoring model could provide prognostic and potentially predictive information for HCC. SDC3, NCF2, BTN3A3, and WARS were noticed as a novel prognostic factor for HCC.
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http://dx.doi.org/10.3389/fmolb.2021.636991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8181399PMC
May 2021

Influence of Ectopic Beats on Heart Rate Variability Analysis.

Entropy (Basel) 2021 May 22;23(6). Epub 2021 May 22.

The State Key Laboratory of Bioelectronics, School of Instrument Science and Engineering, Southeast University, Nanjing 210096, China.

The analysis of heart rate variability (HRV) plays a dominant role in the study of physiological signal variability. HRV reflects the information of the adjustment of sympathetic and parasympathetic nerves on the cardiovascular system and, thus, is widely used to evaluate the functional status of the cardiovascular system. Ectopic beats may affect the analysis of HRV. However, the quantitative relationship between the burden of ectopic beats and HRV indices, including entropy measures, has not yet been investigated in depth. In this work, we analyzed the effects of different numbers of ectopic beats on several widely accepted HRV parameters in time-domain (SDNN), frequency-domain (LF/HF), as well as non-linear features (SampEn and Pt-SampEn (physical threshold-based SampEn)). The results showed that all four indices were influenced by ectopic beats, and the degree of influence was roughly increased with the increase of the number of ectopic beats. Ectopic beats had the greatest impact on the frequency domain index LF/HF, whereas the Pt-SampEn was minimally accepted by ectopic beats. These results also indicated that, compared with the other three indices, Pt-SampEn had better robustness for ectopic beats.
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http://dx.doi.org/10.3390/e23060648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224602PMC
May 2021

Canopy Fibroblast Growth Factor Signaling Regulator 2 (CNPY2) Inhibits Neuron Apoptosis in Parkinson's Disease via AKT/GSK3β pathway.

Curr Neurovasc Res 2021 May 31. Epub 2021 May 31.

Department of Neurology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.

Background: Parkinson's disease (PD) is a neurodegenerative disorder caused by the progressive loss of dopaminergic neurons. Canopy fibroblast growth factor signaling regulator 2 (CNPY2) is down-regulated in this disease, but its functions are unknown.

Objective: This study investigates the effects and regulation of CNPY2 in the apoptosis of neurons in PD.

Methods: We established a PD model in vivo by a five consecutive days-injection of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) to mice. In vitro, the human SH-SY5Y neuroblastoma cells, after differentiation, were treated with 1-Methyl-4-phenylpyridinium iodide (MPP+) for modeling. The cells were transfected with a recombinant vector overexpressing CNPY2 followed by MPP+ treatment. Expression of CNPY2 and proteins related to apoptosis was detected by real-time PCR, western blot, or immunofluorescence staining. The ROS level and mitochondrial membrane potential were determined by flow cytometry. Cell viability and apoptosis were measured by MTT assay and TUNEL staining.

Results: CNPY2 level was down-regulated both in the brain and retina of PD mice and also inhibited in neurons by MPP+ in vitro. Overexpression of CNPY2 repressed the level of Bax and cleaved caspase-3, enhanced Bcl-2 level, and promoted neurite length under MPP+ treatment. CNPY2 overexpression reduced the accumulation of ROS and mitochondria dysfunction in neurons. The AKT/GSK3β signaling pathway was activated by overexpressed CNPY2 to inhibit MPP+-induced neuronal apoptosis, which was confirmed using an AKT inhibitor MK-2206 2HCl.

Conclusion: CNPY2 alleviates oxidative stress, mitochondria dysfunction, and apoptosis of neurons induced by MPP+ by activating the AKT/ GSK3β signaling pathway.
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http://dx.doi.org/10.2174/1567202618666210531141833DOI Listing
May 2021

Resilience as the Mediating Factor in the Relationship Between Sleep Disturbance and Post-stroke Depression of Stroke Patients in China: A Structural Equation Modeling Analysis.

Front Psychiatry 2021 10;12:625002. Epub 2021 May 10.

Department of Social Medicine, School of Public Health, China Medical University, Shenyang, China.

Stroke patients may suffer from a variety of symptoms which can result in sleep disturbance and post-stroke depression (PSD). Whereas, resilience can alleviate sleep disturbance and help maintain well-being after stroke. The aim of this study is to explore whether resilience plays a mediating role in the relationship between sleep disturbance and PSD of stroke patients in China. A cross-sectional study with a multi-stage sampling was carried out in Liaoning Rehabilitation Center and the Third People's Hospital of Chongqing in China from May to September 2019. A total of 353 stroke patients were enrolled in this study. Structural equation model (SEM) was used to test the mediating effect of resilience on the relationship between sleep disturbance and PSD. The prevalence of PSD of stroke patients was 34.56%. Sleep disturbance contributed most to the variance of PSD and had a significantly positive association with PSD among stroke patients ( < 0.01). Resilience was negatively associated with PSD, and acted as a mediator between sleep disturbance and PSD (a b = 0.201, BCa 95% CI: 0.156~0.254). The prevalence of PSD was high among the Chinese stroke patients. Sleep disturbance was highly associated with PSD, resulting in the increased risk of PSD. Furthermore, resilience has a mediating effect on the relationship between sleep disturbance and PSD, and could reduce the negative effect of sleep disturbance on the development of PSD.
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http://dx.doi.org/10.3389/fpsyt.2021.625002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141619PMC
May 2021

Coping Styles for Mediating the Effect of Resilience on Depression Among Medical Students in Web-Based Classes During the COVID-19 Pandemic: Cross-sectional Questionnaire Study.

J Med Internet Res 2021 06 7;23(6):e25259. Epub 2021 Jun 7.

Department of Social Medicine, College of Health Management, China Medical University, Shenyang, Liaoning Province, China.

Background: Due to strict, nationwide, comprehensive COVID-19 protective measures, including home quarantine, all Chinese medical students began taking web-based classes beginning in the spring semester of 2020. Home quarantine, web-based classes, and the stress surrounding the COVID-19 pandemic may have triggered an increased incidence of mental health problems among medical students. Although there have been increasing amounts of literature on depression among medical students, studies focusing on positive psychological resources, such as resilience during the COVID-19 pandemic, still need to be expanded.

Objective: This study aims to assess depression among medical students who are taking web-based classes during the COVID-19 pandemic and to investigate the role of coping styles as mediators between resilience and depression.

Methods: A cross-sectional study of 666 medical students involving stratified sampling in Shenyang, Liaoning Province, China, was completed between March 20 and April 10, 2020. The participants responded to a self-administered, smartphone-based questionnaire, which included the Patient Health Questionnaire-9, Simplified Coping Style Questionnaire, and Ego Resilience 89 Scale. Hierarchical linear regression and structural equation modeling were used in this study.

Results: The prevalence of depression among the participants was 9.6% (64/666) in this study. The regression analysis revealed that grade (the year in which the medical student was in training) (P=.013), how well students adapted to web-based classes (P<.001), their levels of resilience (P=.04), and their coping styles were independent predictors for depression (P<.001). Resilience and positive coping styles were negatively related to depression (resilience: P=.04; positive coping styles: P<.001), and negative coping styles were positively related to depression (P<.001). The structural equation modeling analysis showed that the effect of resilience on depression was partially mediated by coping styles (P=.007).

Conclusions: In this study, it was found that the prevalence of depression was slightly low and coping styles mediated the association between resilience and depression among medical students during the COVID-19 pandemic. These findings have significant implications for future studies. Future studies and interventions should aim to improve resilience and promote positive coping styles.
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http://dx.doi.org/10.2196/25259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189284PMC
June 2021

GABRP sustains the stemness of triple-negative breast cancer cells through EGFR signaling.

Cancer Lett 2021 Aug 21;514:90-102. Epub 2021 May 21.

State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, 650203, China; KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, 650203, China; Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, Yunnan, 650203, China. Electronic address:

Effective treatment regimens for triple-negative breast cancer (TNBC) are relatively scarce due to a lack of specific therapeutic targets. Epidermal growth factor receptor (EGFR) signaling is highly active in TNBC and is associated with poor prognosis. Most EGFR antagonists, which significantly improve outcome in lung and colon cancer, have shown limited clinical effects in breast cancer. However, limiting EGFR expression in TNBC is a potential strategy for improving the clinical efficacy of EGFR antagonists. Here, we found that the gamma-aminobutyric acid type A receptor π subunit (GABRP), as a membrane protein enriched in TNBC stem cells, interacted with EGFR and significantly sustained its expression, resulting in stemness maintenance and chemotherapy resistance. Silencing GABRP induced down-regulation of EGFR signaling, which hindered cell stemness and enhanced sensitivity to chemotherapies, including paclitaxel, doxorubicin, and cisplatin. We also identified that retigabine, an FDA-approved drug for adjunctive treatment of seizures, increased the sensitivity of EGFR to gefitinib in gefitinib-resistant cells. Our findings show that GABRP can sustain the stemness of TNBC via modulating EGFR expression, suggesting that GABRP may be a potential therapeutic target that can address EGFR inhibitor resistance in TNBC.
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http://dx.doi.org/10.1016/j.canlet.2021.04.028DOI Listing
August 2021

Berberine Attenuates Cerebral Ischemia-Reperfusion Injury Induced Neuronal Apoptosis by Down-Regulating the CNPY2 Signaling Pathway.

Front Pharmacol 2021 28;12:609693. Epub 2021 Apr 28.

Department of Central Laboratory, Tianjin 4th Centre Hospital, The Fourth Central Hospital Affiliated to Nankai University, Tianjin, China.

Berberine (BBR) has a neuroprotective effect against ischemic stroke, but its specific protective mechanism has not been clearly elaborated. This study explored the effect of BBR on the canopy FGF signaling regulator 2 (CNPY2) signaling pathway in the ischemic penumbra of rats. The model of cerebral ischemia-reperfusion injury (CIRI) was established by the thread embolization method, and BBR was gastrically perfused for 48 h or 24 h before operation and 6 h after operation. The rats were randomly divided into four groups: the Sham group, BBR group, CIRI group, and CIRI + BBR group. After 2 h of ischemia, followed by 24 h of reperfusion, we confirmed the neurologic dysfunction and apoptosis induced by CIRI in rats ( < 0.05). In the ischemic penumbra, the expression levels of CNPY2-regulated endoplasmic reticulum stress-induced apoptosis proteins (CNPY2, glucose-regulated protein 78 (GRP78), double-stranded RNA-activated protein kinase-like ER kinase (PERK), C/EBP homologous protein (CHOP), and Caspase-3) were significantly increased, but these levels were decreased after BBR treatment ( < 0.05). To further verify the inhibitory effect of BBR on CIRI-induced neuronal apoptosis, we added an endoplasmic reticulum-specific agonist and a PERK inhibitor to the treatment. BBR was shown to significantly inhibit the expression of apoptotic proteins induced by endoplasmic reticulum stress agonist, while the PERK inhibitor partially reversed the ability of BBR to inhibit apoptotic protein ( < 0.05). These results confirm that berberine may inhibit CIRI-induced neuronal apoptosis by downregulating the CNPY2 signaling pathway, thereby exerting a neuroprotective effect.
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http://dx.doi.org/10.3389/fphar.2021.609693DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113774PMC
April 2021

Low-threshold and controllable nanolaser based on quasi-BIC supported by an all-dielectric eccentric nanoring structure.

Opt Express 2021 Apr;29(8):12634-12643

High-Q factor can enhance the interaction between light and matter, which is an important parameter to decrease the threshold of nanolasers. Here, we theoretically propose an eccentric nanoring structure with a high and controllable Q factor to realize a low-threshold and controllable nanolaser by amplifying the quasi-bound states in the continuum (quasi-BIC). The designed nanostructure supports a quasi-BIC because of the symmetry protection-breaking of the nanostructure. The quasi-BIC has a very high Q factor of about 9.6×10 and can also be adjusted by changing structural parameters. We use the energy level diagram of the four-level two-electron system to study the lasing action of the eccentric nanoring structure. The results show that the nanolaser has a relatively low threshold of about 6.46 μJ/cm. Furthermore, the lasing behavior can be tuned by controlling the structural parameters of the eccentric circular ring structure.
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http://dx.doi.org/10.1364/OE.420001DOI Listing
April 2021

Exosomal miR-486-5p derived from human placental microvascular endothelial cells regulates proliferation and invasion of trophoblasts via targeting IGF1.

Hum Cell 2021 May 11. Epub 2021 May 11.

Department of Obstetrics, Guangdong Woman and Children Hospital, No. 521 Xingnan Avenue, Guangzhou, 510000, Guangdong, China.

Preeclampsia (PE) is a serious complication of pregnancy. Exosomes are known to be upregulated in PE. In this study, we sought to investigate the effect of miR-486-5p from human placental microvascular endothelial cells, on the function of trophoblast cells. To investigate the function of human placental microvascular endothelial cell (HPVEC)-derived exosomes on trophoblast cells, HPVECs were treated with hypoxia/reoxygenation (H/R). The separation efficiency of exosomes was determined by transmission electron microscopy, nanosight and Western blot. Cell Counting Kit-8, EdU staining, wound-healing, and transwell assay were performed to detect the effect of exosomally transferred miR-486-5p inhibitor on proliferation, migration and invasion of trophoblast cells. MiRDB and dual-luciferase report assay were used to find the target of miR-486-5p. Our data revealed that miR-486-5p was significantly upregulated in H/R-treated HPVEC-Exo, and miR-486-5p was enriched in HPVEC-Exo. miR-486-5p inhibitor carried by HPVEC-Exo significantly inhibited the proliferation, migration and invasion of trophoblast cells. Insulin-like growth factor 1 (IGF1) was found to be the target of miR-486-5p, and IGF1 overexpression notably reversed the effect of miR-486-5p inhibitor from HPVEC-Exo on trophoblast cell function. In summary, H/R-treated HPVEC-derived exosomally expressing miR-486-5p inhibitor significantly inhibited the proliferation, migration and invasion of trophoblast cells via downregulation of IGF1. The findings from the present study may be useful in the development of treatments for PE.
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http://dx.doi.org/10.1007/s13577-021-00543-xDOI Listing
May 2021

Gut microbiota modulation and anti-inflammatory properties of mixed lactobacilli in dextran sodium sulfate-induced colitis in mice.

Food Funct 2021 Jun;12(11):5130-5143

Key Laboratory of Dairy Science, Ministry of Education, Northeast Agricultural University, Harbin 150030, China. and Food College, Northeast Agricultural University, Harbin 150030, China.

Correlations between gut microbiota activities and inflammatory bowel disease (IBD) treatment are gaining research interest. In our previous study, Lactobacillus acidophilus KLDS 1.0901, Lactobacillus helveticus KLDS 1.8701, and Lactobacillus plantarum KLDS 1.0318 showed antibacterial, antioxidant, and immunomodulatory activities. In the current study, we evaluated the effects of three tested strains and their mixture on dextran sulfate sodium (DSS)-induced colitis in C57BL/6J mice. The three tested strains and their mixture significantly decreased the disease activity index (DAI), colon shortening, and myeloperoxidase (MPO) activity. Additionally, the three tested strains and their mixture improved the histological damage, increased the colonic mucous layer integrity, and exhibited lower levels of prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), while up-regulating colonic anti-inflammatory cytokine IL-10 levels, tight junction proteins (E-cadherin, zonulae occludens (ZO)-1, occludin and claudin-1) and mucin (MUC1 and MUC2) mRNA expressions to some extent. In addition, mixed lactobacilli showed better anti-inflammatory effects than single-strain treatment. Our study further revealed that mixed lactobacilli increased bacterial diversity and improved gut microbiota composition, increasing short-chain fatty acid (SCFA) production. These results indicated that mixed lactobacilli supplementation could attenuate DSS-induced colitis by modulating the gut microbiota and repairing the intestinal barrier, which provided a scientific basis for its clinical application in the future.
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http://dx.doi.org/10.1039/d1fo00317hDOI Listing
June 2021

Plasma hemoglobin and the risk of death in HIV/AIDS patients treated with antiretroviral therapy.

Aging (Albany NY) 2021 05 7;13(9):13061-13072. Epub 2021 May 7.

Department of Preventive Medicine, School of Public Health and Management, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China.

Background: Previous studies concerning the effect of plasma hemoglobin (HB) and other factors that may modify the risk of death in people living with HIV/AIDS (PLHIV) treated with antiretroviral therapy (ART) are limited.

Results: Higher HB was independently linked to a lower death risk in PLHIV, with a decrease of 29% (13%, 43%) per standard deviation (SD) increment after adjusting for CD4, VL and other potential factors [hazard ratio (HR): 0.71, 95% confidence interval (CI): 0.57-0.87, P<0.001]. In addition, the addition of HB to the predictive model containing VL and CD4 significantly improved the C-index, by 0.69% (95% CI: 0.68%-0.71%), and net discrimination, by 0.5% (95% CI: 0.0%-1.6%, P=0.040), when predicting the death risk of PLHIV.

Conclusions: A lower level of HB was an independent risk factor for HIV/AIDS-associated death in PLHIV. HB combined with VL and CD4 may be an appropriate predictive model of the death risk of PLHIV.

Materials And Methods: A propensity-score matching (PSM) approach was applied to select a total of 750 PLHIV (150 deceased and 600 living) from the AIDS prevention and control information system in the Wenzhou area from 2006 to 2018. Multivariable Cox proportional hazards regression models were formulated to estimate the effect of HB. The predictive performance improvement contributed by HB was evaluated using the C-index and net reclassification improvement.
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http://dx.doi.org/10.18632/aging.202987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148493PMC
May 2021

Heterozygous Recurrent Mutations Inducing Dysfunction of Gene in Patients With Short Stature.

Front Cell Dev Biol 2021 14;9:661747. Epub 2021 Apr 14.

Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.

Purpose: ROR2, a member of the ROR family, is essential for skeletal development as a receptor of Wnt5a. The present study aims to investigate the mutational spectrum of in children with short stature and to identify the underlying molecular mechanisms.

Methods: We retrospectively analyzed clinical phenotype and whole-exome sequencing (WES) data of 426 patients with short stature through mutation screening of . We subsequently examined the changes in protein expression and subcellular location in caused by the mutations. The mRNA expression of downstream signaling molecules of the Wnt5a-ROR2 pathway was also examined.

Results: We identified 12 mutations in in 21 patients, including 10 missense, one nonsense, and one frameshift. Among all missense variants, four recurrent missense variants [c.1675G > A(p.Gly559Ser), c.2212C > T(p.Arg738Cys), c.1930G > A(p.Asp644Asn), c.2117G > A(p.Arg706Gln)] were analyzed by experiments . The c.1675G > A mutation significantly altered the expression and the cellular localization of the ROR2 protein. The c.1675G > A mutation also caused a significantly decreased expression of c-Jun. In contrast, other missense variants did not confer any disruptive effect on the biological functions of ROR2.

Conclusion: We expanded the mutational spectrum of in patients with short stature. Functional experiments potentially revealed a novel molecular mechanism that the c.1675G > A mutation in might affect the expression of downstream Wnt5a-ROR2 pathway gene by disturbing the subcellular localization and expression of the protein.
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http://dx.doi.org/10.3389/fcell.2021.661747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080376PMC
April 2021

Development and Validation of a Clinical Prediction Model for Sleep Disorders in the ICU: A Retrospective Cohort Study.

Front Neurosci 2021 16;15:644845. Epub 2021 Apr 16.

The Third Central Clinical College of Tianjin Medical University, Tianjin, China.

Background: Sleep disorders, the serious challenges faced by the intensive care unit (ICU) patients are important issues that need urgent attention. Despite some efforts to reduce sleep disorders with common risk-factor controlling, unidentified risk factors remain.

Objectives: This study aimed to develop and validate a risk prediction model for sleep disorders in ICU adults.

Methods: Data were retrieved from the MIMIC-III database. Matching analysis was used to match the patients with and without sleep disorders. A nomogram was developed based on the logistic regression, which was used to identify risk factors for sleep disorders. The calibration and discrimination of the nomogram were evaluated with the 1000 bootstrap resampling and receiver operating characteristic curve (ROC). Besides, the decision curve analysis (DCA) was applied to evaluate the clinical utility of the prediction model.

Results: 2,082 patients were included in the analysis, 80% of whom ( = 1,666) and the remaining 20% ( = 416) were divided into the training and validation sets. After the multivariate analysis, hemoglobin, diastolic blood pressure, respiratory rate, cardiovascular disease, and delirium were the independent risk predictors for sleep disorders. The nomogram showed high sensitivity and specificity of 75.6% and 72.9% in the ROC. The threshold probability of the net benefit was between 55% and 90% in the DCA.

Conclusion: The model showed high performance in predicting sleep disorders in ICU adults, the good clinical utility of which may be a useful tool for providing clinical decision support to improve sleep quality in the ICU.
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http://dx.doi.org/10.3389/fnins.2021.644845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085546PMC
April 2021

Variants Affecting the C-Terminal of CSF1R Cause Congenital Vertebral Malformation Through a Gain-of-Function Mechanism.

Front Cell Dev Biol 2021 19;9:641133. Epub 2021 Mar 19.

Department of Orthopedic Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.

encodes the colony-stimulating factor 1 receptor which regulates the proliferation, differentiation, and biological activity of monocyte/macrophage lineages. Pathogenic variants in could lead to autosomal dominant adult-onset leukoencephalopathy with axonal spheroids and pigmented glia or autosomal recessive skeletal dysplasia. In this study, we identified three heterozygous deleterious rare variants in from a congenital vertebral malformation (CVM) cohort. All of the three variants are located within the carboxy-terminal region of CSF1R protein and could lead to an increased stability of the protein. Therefore, we established a zebrafish model overexpressing . The zebrafish model exhibits CVM phenotypes such as hemivertebral and vertebral fusion. Furthermore, overexpression of the mutated mRNA depleted of the carboxy-terminus led to a higher proportion of zebrafish with vertebral malformations than wild-type CSF1R mRNA did ( = 0.03452), implicating a gain-of-function effect of the C-terminal variant. In conclusion, variants affecting the C-terminal of CSF1R could cause CVM though a potential gain-of-function mechanism.
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http://dx.doi.org/10.3389/fcell.2021.641133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017210PMC
March 2021

Association Between the Presence of Female-Specific Tumors and Aggressive Clinicopathological Features in Papillary Thyroid Cancer: A Retrospective Analysis of 9,822 Cases.

Front Oncol 2021 11;11:611471. Epub 2021 Mar 11.

Division of Thyroid Surgery, China-Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Surgical Translational Medicine, Jilin Provincial Engineering Laboratory of Thyroid Disease Prevention and Control, Changchun, China.

Objective: To investigate the association between the presence of female-specific tumors and aggressive clinicopathological features in papillary thyroid cancer (PTC).

Methods: This study retrospectively analyzed 9,822 female cases between June 2008 and December 2017. Odds ratios and corresponding 95% confidence intervals were calculated. Findings were stratified by age and body mass index (BMI) in different models.

Results: 1443/9822 (14.7%) patients with PTC had a female-specific tumor. Presence of a benign breast mass was an independent risk factor for a primary PTC lesion > 1 cm in diameter (adjusted OR = 1.446, 95% CI 1.136-1.840, = 0.003), but a protective factor against extrathyroidal extension of PTC (adjusted OR = 0.650, 95%CI 0.500-0.845, = 0.001). Presence of a benign uterine mass was an independent risk factor for multifocal PTC (adjusted OR = 1.305, 95%CI 1.113-1.531, = 0.001). Analyses stratified by age and BMI revealed the presence of a benign breast mass was an independent risk factor for a primary PTC lesion > 1 cm in diameter in patients aged <36 years (adjusted OR = 1.711, 95% CI 1.063-2.754, = 0.027), and a protective factor against extrathyroidal extension of PTC in patients aged ≥36 - <42 years (OR adjusted = 0.533, 95% CI 0.302-0.941, = 0.030) or with a BMI ≥ 23.4 kg/m (BMI ≥ 23.4 to < 25.7 kg/m, adjusted OR = 0.441, 95% CI 0.246-0.792, = 0.006; BMI ≥25.7 kg/m, adjusted OR = 0.558, 95% CI 0.315-0.998, = 0.045). Presence of a benign uterine mass was an independent risk factor for multifocal PTC in patients aged ≥49 years (adjusted OR = 1.397, 95% CI 1.088-1.793, = 0.009) or with a BMI <21.5 kg/m (OR adjusted = 1.745, 95% CI 1.214-2.509, = 0.003).

Conclusion: The presence of a benign breast mass was an independent risk factor for a primary PTC lesion > 1 cm in diameter and a protective factor against extrathyroidal extension of PTC, while the presence of a benign uterine mass was an independent risk factor for multifocal PTC. Data from this study may help surgeons propose more personalized treatment plans when encountering patients with PTC and female-specific benign tumors.
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http://dx.doi.org/10.3389/fonc.2021.611471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006326PMC
March 2021

DNA metabarcoding of zooplankton communities: species diversity and seasonal variation revealed by 18S rRNA and COI.

PeerJ 2021 19;9:e11057. Epub 2021 Mar 19.

College of Life Sciences, Shaanxi Normal University, Xian, Shaanxi, China.

Background: Zooplankton is an important component of aquatic organisms and has important biological and economical significance in freshwater ecosystems. However, traditional methods that rely on morphology to classify zooplankton require expert taxonomic skills. Moreover, traditional classification methods are time-consuming and labor-intensive, which is not practical for the design of conservation measures and ecological management tools based on zooplankton diversity assessment.

Methods: We used DNA metabarcoding technology with two different markers: the nuclear small subunit ribosomal RNA (18S rRNA) and mitochondrial cytochrome c oxidase (COI), to analyze 72 zooplankton samples collected in 4 seasons and 9 locations from the Sanmenxia Reservoir. We investigated seasonal changes in the zooplankton community and their relationship with water environmental factors.

Results: A total of 190 species of zooplankton were found, belonging to 12 phyla, 24 classes, 61 orders, 111 families, and 174 genera. Protozoa, especially ciliates, were the most diverse taxa. Richness and relative abundance of zooplankton showed significant seasonal changes. Both alpha and beta diversity showed seasonal trends: the diversity in summer and autumn was higher than that in winter and spring. The zooplankton diversity was most similar in winter and spring. By correlating metabarcoding data and water environmental factors, we proved that water temperature, chemical oxygen demand, total nitrogen and ammoniacal nitrogen were the main environmental factors driving the seasonal changes in zooplankton in the Sanmenxia Reservoir. Water temperature, followed by total nitrogen, were the most influential factors. This study highlights the advantages and some limitations of zooplankton molecular biodiversity assessment using two molecular markers.
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http://dx.doi.org/10.7717/peerj.11057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7983862PMC
March 2021

CRISPR/Cas9-based discovery of maize transcription factors regulating male sterility and their functional conservation in plants.

Plant Biotechnol J 2021 Mar 27. Epub 2021 Mar 27.

Zhongzhi International Institute of Agricultural Biosciences, Biology and Agriculture Research Center of USTB, University of Science and Technology Beijing (USTB), Beijing, China.

Identifying genic male-sterility (GMS) genes and elucidating their roles are important to unveil plant male reproduction and promote their application in crop breeding. However, compared with Arabidopsis and rice, relatively fewer maize GMS genes have been discovered and little is known about their regulatory pathways underlying anther and pollen development. Here, by sequencing and analysing anther transcriptomes at 11 developmental stages in maize B73, Zheng58 and M6007 inbred lines, 1100 transcription factor (TF) genes were identified to be stably differentially expressed among different developmental stages. Among them, 14 maize TF genes (9 types belonging to five TF families) were selected and performed CRISPR/Cas9-mediated gene mutagenesis, and then, 12 genes in eight types, including ZmbHLH51, ZmbHLH122, ZmTGA9-1/-2/-3, ZmTGA10, ZmMYB84, ZmMYB33-1/-2, ZmPHD11 and ZmLBD10/27, were identified as maize new GMS genes by using DNA sequencing, phenotypic and cytological analyses. Notably, ZmTGA9-1/-2/-3 triple-gene mutants and ZmMYB33-1/-2 double-gene mutants displayed complete male sterility, but their double- or single-gene mutants showed male fertility. Similarly, ZmLBD10/27 double-gene mutant displayed partial male sterility with 32.18% of aborted pollen grains. In addition, ZmbHLH51 was transcriptionally activated by ZmbHLH122 and their proteins were physically interacted. Molecular markers co-segregating with these GMS mutations were developed to facilitate their application in maize breeding. Finally, all 14-type maize GMS TF genes identified here and reported previously were compared on functional conservation and diversification among maize, rice and Arabidopsis. These findings enrich GMS gene and mutant resources for deeply understanding the regulatory network underlying male fertility and for creating male-sterility lines in maize.
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http://dx.doi.org/10.1111/pbi.13590DOI Listing
March 2021

Human milk and infant formula modulate the intestinal microbiota and immune systems of human microbiota-associated mice.

Food Funct 2021 Mar 10;12(6):2784-2798. Epub 2021 Mar 10.

Food College, Northeast Agricultural University, Harbin 150030, China.

Many infants on an exclusive breastfeeding regimen are often fed inadequate amounts, and this creates an imbalance between the overall effects of breast milk and commercial infant formulas. We comparatively analyzed the impact of human milk and two infant formulas in modulating the intestinal microbiota and the immune systems of mice colonized by healthy infant feces. The results showed that compared to infant formula, human milk decreased the levels of alanine transaminase, alkaline phosphatase, and total protein. Also, it improved the immune system through the level of cytokines (CD4+ lymphocytes, Th1, Th2, Th17, and Treg cells) and immunity indicators (IL-2, IL-4, IL-9, and sIgA). Human milk decreased intestinal mucosal permeability compared to infant formula. Bacterial 16S rRNA gene sequence analysis revealed that human milk increased the abundance of Akkermansia and Bacteroides, while infant formula increased the abundance of Lactobacillus and Escherichia_Shigella. Collectively, our results showed that human milk is more suitable for infants than the two commercial infant formulas based on intestinal microbiota and immune system analyses. These findings thus support a theoretical basis for the development of infant formulas.
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http://dx.doi.org/10.1039/d0fo03004jDOI Listing
March 2021
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