Publications by authors named "Yue Gao"

743 Publications

DAN: Deep-Attention Network for 3D Shape Recognition.

IEEE Trans Image Process 2021 Apr 13;PP. Epub 2021 Apr 13.

Due to the wide applications in a rapidly increasing number of different fields, 3D shape recognition has become a hot topic in the computer vision field. Many approaches have been proposed in recent years. However, there remain huge challenges in two aspects: exploring the effective representation of 3D shapes and reducing the redundant complexity of 3D shapes. In this paper, we propose a novel deep-attention network (DAN) for 3D shape representation based on multiview information. More specifically, we introduce the attention mechanism to construct a deep multiattention network that has advantages in two aspects: 1) information selection, in which DAN utilizes the self-attention mechanism to update the feature vector of each view, effectively reducing the redundant information, and 2) information fusion, in which DAN applies attention mechanism that can save more effective information by considering the correlations among views. Meanwhile, deep network structure can fully consider the correlations to continuously fuse effective information. To validate the effectiveness of our proposed method, we conduct experiments on the public 3D shape datasets: ModelNet40, ModelNet10, and ShapeNetCore55. Experimental results and comparison with state-of-the-art methods demonstrate the superiority of our proposed method. Code is released on https://github.com/RiDang/DANN.
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http://dx.doi.org/10.1109/TIP.2021.3071687DOI Listing
April 2021

Core-Shell Tecto Dendrimers Enable Enhanced Tumor MR Imaging through an Amplified EPR Effect.

Biomacromolecules 2021 Apr 13. Epub 2021 Apr 13.

State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, People's Republic of China.

Development of nanoplatforms that can amplify the passive tumor targeting effect based on enhanced permeability and retention (EPR) effect is crucial for precision cancer nanomedicine applications. Herein, we present the development of core-shell tecto dendrimers (CSTDs) as a platform for enhanced tumor magnetic resonance (MR) imaging through an amplified EPR effect. In this work, poly(amidoamine) (PAMAM) dendrimers of generation 5 (G5) were decorated with β-cyclodextrin (CD) and then assembled with G3 PAMAM dendrimers premodified with adamantane (Ad) via supramolecular recognition of CD and Ad. The formed G5-CD/Ad-G3 CSTDs were conjugated with tetraazacyclododecane tetraacetic acid (DOTA)-Gd(III) chelators and further acetylated to neutralize the remaining CSTD periphery amines. We reveal that the formed CSTD.NHAc-DOTA(Gd) (CSTD-D-Gd) complexes have a narrow size distribution and satisfactory colloidal stability, and are cytocompatible within the concentration range studied. Compared to the single dendrimer counterpart of G5.NHAc-DOTA(Gd) (G5-D-Gd) complexes, the CSTD-D-Gd complexes with a higher molecular weight and volume possess a longer rotation correlation time, hence having a longitudinal relaxivity () of 7.34 mM s, which is 1.5 times larger than that of G5-D-Gd complexes (4.92 mM s). More importantly, the CSTD-D-Gd complexes display better permeability in the three-dimensional (3D) cell spheroids through fluorescence imaging and a more significant EPR effect for improved tumor MR imaging than the G5-DOTA-Gd complexes. The generated CSTD-D-Gd complexes may be adopted for enhanced tumor MR imaging through an amplified passive EPR effect and also be further extended for different cancer theranostic applications.
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http://dx.doi.org/10.1021/acs.biomac.1c00262DOI Listing
April 2021

Early identification of patients with severe COVID-19 at increased risk of in-hospital death: a multicenter case-control study in Wuhan.

J Thorac Dis 2021 Mar;13(3):1380-1395

Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing, China.

Background: Most evidence regarding the risk factors for early in-hospital mortality in patients with severe COVID-19 focused on laboratory data at the time of hospital admission without adequate adjustment for confounding variables. A multicenter, age-matched, case-control study was therefore designed to explore the dynamic changes in laboratory parameters during the first 10 days after admission and identify early risk indicators for in-hospital mortality in this patient cohort.

Methods: Demographics and clinical data were extracted from the medical records of 93 pairs of patients who had been admitted to hospital with severe COVID-19. These patients had either been discharged or were deceased by March 3, 2020. Data from days 1, 4, 7, and 10 of hospital admission were compared between survivors and non-survivors. Univariate and multivariate conditional logistic regression analyses were employed to identify early risk indicators of in-hospital death in this cohort.

Results: On admission, in-hospital mortality was associated with five risk indicators (ORs in descending order): aspartate aminotransferase (AST, >32 U/L) 43.20 (95% CI: 2.63, 710.04); C-reactive protein (CRP) greater than 100 mg/L 13.61 (1.78, 103.941); lymphocyte count lower than 0.6×10/L 9.95 (1.30, 76.42); oxygen index (OI) less than 200 8.23 (1.04, 65.15); and D-dimer over 1 mg/L 8.16 (1.23, 54.34). Sharp increases in D-dimer at day 4, accompanied by decreasing lymphocyte counts, deteriorating OI, and persistent remarkably high CRP concentration were observed among non-survivors during the early stages of hospital admission.

Conclusions: The potential risk factors of high D-dimer, CRP, AST, low lymphocyte count and OI could help clinicians identify patients at high risk of death early in the hospital admission. This might assist with rationalization of health care resources.
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http://dx.doi.org/10.21037/jtd-20-2568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024856PMC
March 2021

Improving Eye-Computer Interaction Interface Design: Ergonomic Investigations of the Optimum Target Size and Gaze-triggering Dwell Time.

J Eye Mov Res 2020 Sep 25;12(3). Epub 2020 Sep 25.

School of Mechanical Engineering, Southeast University, China.

Interactive feedback of interface elements and low level of spatial accuracy are two main key points for the interaction research in the Eye-computer interaction system. This study tried to solve these two problems from the perspective of human-computer interactions and ergonomics. Two experiments were conducted to explore the optimum target size and gaze-triggering dwell time of the eye-computer interaction (ECI) system. Experimental Series 1 was used as the pre-experiment to identify the size that has a greater task completion rate. Experimental Series 2 was used as the main experiment to investigate the optimum gaze-triggering dwell time by using a comprehensive evaluation of the task completion rate, reaction time, and NASA-TLX (Task Load Index). In Experimental Series 1, the optimal element size was determined to be 256 × 256p x 2. The conclusion of Experimental Series 2 was that when the dwell time is set to 600 ms, the efficiency of the interface is the highest, and the task load of subjects is minimal as well. Finally, the results of Experiment Series 1 and 2 have positive effects on improving the usability of the interface. The optimal control size and the optimal dwell time obtained from the experiments have certain reference and application value for interface design and software development of the ECI system.
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http://dx.doi.org/10.16910/jemr.12.3.8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880147PMC
September 2020

PXR mediates mifepristone-induced hepatomegaly in mice.

Acta Pharmacol Sin 2021 Mar 29. Epub 2021 Mar 29.

Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.

Mifepristone (Mif), an effective synthetic steroidal antiprogesterone drug, is widely used for medical abortion and pregnancy prevention. Due to its anti-glucocorticoid effect, high-dose Mif is also used to treat Cushing's syndrome. Mif was reported to active pregnane X receptor (PXR) in vitro and PXR can induce hepatomegaly via activation and interaction with yes-associated protein (YAP) pathway. High-dose Mif was reported to induce hepatomegaly in rats and mice, but the underlying mechanism remains unclear. Here, the role of PXR was studied in Mif-induced hepatomegaly in C57BL/6 mice and Pxr-knockout mice. The results demonstrated that high-dose Mif (100 mg · kg · d, i.p.) treatment for 5 days significantly induced hepatomegaly with enlarged hepatocytes and promoted proliferation, but low dose of Mif (5 mg · kg · d, i.p.) cannot induce hepatomegaly. The dual-luciferase reporter gene assays showed that Mif can activate human PXR in a concentration-dependent manner. In addition, Mif could promote nuclear translocation of PXR and YAP, and significantly induced the expression of PXR, YAP, and their target proteins such as CYP3A11, CYP2B10, UGT1A1, ANKRD, and CTGF. However, Mif (100 mg · kg · d, i.p.) failed to induce hepatomegaly in Pxr-knockout mice, as well as hepatocyte enlargement and proliferation, further indicating that Mif-induced hepatomegaly is PXR-dependent. In summary, this study demonstrated that PXR-mediated Mif-induced hepatomegaly in mice probably via activation of YAP pathway. This study provides new insights in Mif-induced hepatomegaly, and provides novel evidence on the crucial function of PXR in liver enlargement and regeneration.
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http://dx.doi.org/10.1038/s41401-021-00633-4DOI Listing
March 2021

Regulation of RDN on Th1/ILC1 cell imbalance in HFMD patients caused by EV71 infection.

Chin J Nat Med 2021 Mar;19(3):205-211

Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China. Electronic address:

Enterovirus 71 (EV71) infection is more likely to cause hand, foot and mouth disease (HFMD) in children, which can lead to neurogenic complications and higher mortality. As a commonly used clinical medicine, Reduning injection (RDN) helps to shorten the symptoms of patients with HFMD and facilitate the early recovery of children. However, the regulatory mechanism of RDN on the HFMD immune system disorder caused by EV71 remains to be discussed. This study collected detailed treatment data of 56 children with HFMD who entered the affiliated Children's Hospital of Nanjing Medical University during 2019. Retrospective analysis of clinical data showed that the symptoms of the RDN treatment group were improved compared with the untreated group. To explore its mechanism, the relevant detection indicators were detected by flow cytometry, enzyme-linked immunosorbent assay and real-time quantitative PCR. It was found that the number and function of innate immune (ILCs) and adaptive immunity (Th1, Th2 and secreted cytokines) were reduced, suggesting that RDN plays a role by regulating cellular immunity. The in vitro differentiation inhibition test further confirmed that RDN affected Th1 differentiation by inhibiting the expression of transcription factors on the basis of Th1 cell differentiation in vitro.
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http://dx.doi.org/10.1016/S1875-5364(21)60022-5DOI Listing
March 2021

Constitutive androstane receptor induced-hepatomegaly and liver regeneration is partially yes-associated protein activation.

Acta Pharm Sin B 2021 Mar 28;11(3):727-737. Epub 2020 Nov 28.

Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.

The constitutive androstane receptor (CAR, NR3I1) belongs to nuclear receptor superfamily. It was reported that CAR agonist TCPOBOP induces hepatomegaly but the underlying mechanism remains largely unknown. Yes-associated protein (YAP) is a potent regulator of organ size. The aim of this study is to explore the role of YAP in CAR activation-induced hepatomegaly and liver regeneration. TCPOBOP-induced CAR activation on hepatomegaly and liver regeneration was evaluated in wild-type (WT) mice, liver-specific YAP-deficient mice, and partial hepatectomy (PHx) mice. The results demonstrate that TCPOBOP can increase the liver-to-body weight ratio in wild-type mice and PHx mice. Hepatocytes enlargement around central vein (CV) area was observed, meanwhile hepatocytes proliferation was promoted as evidenced by the increased number of KI67 cells around portal vein (PV) area. The protein levels of YAP and its downstream targets were upregulated in TCPOBOP-treated mice and YAP translocation can be induced by CAR activation. Co-immunoprecipitation results suggested a potential protein-protein interaction of CAR and YAP. However, CAR activation-induced hepatomegaly can still be observed in liver-specific YAP-deficient () mice. In summary, CAR activation promotes hepatomegaly and liver regeneration partially by inducing YAP translocation and interaction with YAP signaling pathway, which provides new insights to further understand the physiological functions of CAR.
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http://dx.doi.org/10.1016/j.apsb.2020.11.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982502PMC
March 2021

Simvastatin attenuates acute lung injury by activation of A2B adenosine receptor.

Toxicol Appl Pharmacol 2021 Mar 24:115460. Epub 2021 Mar 24.

Department of Respiratory Medicine in Special Wards, Chinese PLA General Hospital, Beijing 100853, China. Electronic address:

To explore the protective mechanism of simvastatin in acute lung injury (ALI), the lipopolysaccharide (LPS) induced (5 mg/kg) ALI rat model was used to examine the effects of simvastatin. Following simvastatin treatment, the histopathological evaluation of lung tissues was made using hematoxylin and eosin (H&E) staining. Also, myeloperoxidase (MPO) activity and the levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and IL-10 were determined by ELISA. Blood gas analyses of arterial blood samples were performed to assess the pulmonary gas exchange. Moreover, the neutrophil count and total protein content were determined in the bronchoalveolar lavage (BAL) fluid. The ratio of wet lung to dry lung (W/D) and the alveolar fluid clearance (AFC) were calculated to estimate the severity of edema. Lastly, the levels of A2BAR, CFTR, claudin4, and claudin18 were also measured by qRT-PCR and Western blotting. Simvastatin treatment, in a dose-related manner, markedly improved the lung histological injury and decreased the levels of TNF-α, IL-1β, and increased IL-10 in LPS induced ALI. Also, pulmonary neutrophil count was alleviated. Besides, a decreased ratio of W/D lung also confirmed the simvastatin intervention. Notably, simvastatin reduced the levels of A2BAR, CFTR, and claudin18 but upregulated claudin4 in lung tissues. Additionally, treatment with PSB1115, an antagonist of A2BAR, countered the protective effect of simvastatin in ALI. Our study demonstrates that simvastatin has a protective effect against LPS-induced ALI by activating A2BAR and should be exploited as a novel therapeutic target for the treatment of ALI.
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http://dx.doi.org/10.1016/j.taap.2021.115460DOI Listing
March 2021

Effects of iron plaque and fatty acids on the transfer of BDE-209 from soil to rice under iron mineral Fenton-like oxidation condition.

Sci Total Environ 2021 Jun 2;772:145554. Epub 2021 Feb 2.

Key Laboratory of Pollution Processes and Environmental Criteria, Ministry of Education, Tianjin Key Laboratory of Environmental Remediation and Pollution Control, College of Environmental Science and Engineering, Nankai University, Tianjin 300071, China.

To understand the effect mechanisms of iron plaque and fatty acids on the migration of PBDEs from soil to rice (Oryza sativa), pot experiments were conducted in the soil spiked with decabromodiphenyl ether (BDE-209) under the conditions of tourmaline and nano-goethite Fenton-like treatments. The results showed that iron mineral Fenton-like oxidation could effectively remove BDE-209 from rhizosphere soil, the highest removal rate obtained 89.29% with the addition of 0.4 mmol/L HO and 8 g nano-goethite (G + 3H group). Iron mineral Fenton-like oxidation could produce iron plaque (IP) on rice roots and accumulate a part of contaminants on the surface of IP, further weakening BDE-209 uptake in the plants. Additionally, the occurrence of fatty acid variation induced by BDE-209 stress, iron mineral Fenton-like oxidation at high concentrations of HO with 0.4 mmol/L affected the distribution of fatty acids in plant tissues, especially for C fatty acid. While the IP on rice roots prevented the BDE-209 into plant, it was also closely related to the distribution of fatty acids in rice, altering BDE-209 accumulation in the rice. To safely use the iron mineral Fenton-like oxidation in the agricultural soil remediation, the safety of plant cells treated by mineral Fenton-like oxidation was evaluated using the transmission electron microscopy (TEM) and enzyme activity determination, which indicated that iron mineral Fenton-like oxidation would destroy the inner structures of plant cells, especially for G + 3H group.
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http://dx.doi.org/10.1016/j.scitotenv.2021.145554DOI Listing
June 2021

Impact of type 2 diabetes mellitus on left ventricular diastolic function in patients with essential hypertension: evaluation by volume-time curve of cardiac magnetic resonance.

Cardiovasc Diabetol 2021 Mar 25;20(1):73. Epub 2021 Mar 25.

Department of Radiology, West China Hospital, Sichuan University, 37# Guo Xue Xiang, Chengdu, 610041, Sichuan, China.

Background: Essential hypertension and type 2 diabetes mellitus (T2DM) are two common chronic diseases that often coexist, and both of these diseases can cause heart damage. However, the additive effects of essential hypertension complicated with T2DM on left ventricle (LV) diastolic function have not been fully illustrated. This study aims to investigate whether T2DM affects the diastolic function of the LV in patients with essential hypertension using the volume-time curve from cardiac magnetic resonance (CMR).

Methods: A total of 124 essential hypertension patients, including 48 with T2DM [HTN(T2DM +) group] and 76 without T2DM [HTN(T2DM-) group], and 52 normal controls who underwent CMR scans were included in this study. LV volume-time curve parameters, including the peak ejection rate (PER), time to peak ejection rate (PET), peak filling rate (PFR), time to peak filling rate from end-systole (PFT), PER normalized to end-diastolic volume (PER/EDV), and PFR normalized to EDV (PFR/EDV), were measured and compared among the three groups. Multivariate linear regression analyses were performed to determine the effects of T2DM on LV diastolic dysfunction in patients with hypertension. Pearson correlation was used to analyse the correlation between the volume-time curve and myocardial strain parameters.

Results: PFR and PFR/EDV decreased from the control group, through HTN(T2DM -), to HTN(T2DM +) group. PFT in the HTN(T2DM-) group and HTN(T2DM +) group was significantly longer than that in the control group. The LV remodelling index in the HTN(T2DM -) and HTN(T2DM +) groups was higher than that in the normal control group, but there was no significant difference between the HTN(T2DM -) and HTN(T2DM +) groups. Multiple regression analyses controlling for covariates of systolic blood pressure, age, sex, and heart rate demonstrated that T2DM was independently associated with PFR/EDV (β = 0.252, p < 0.05). The volume-time curve method has good repeatability, and there is a significant correlation between volume-time curve parameters (PER/EDV and PFR/EDV) and myocardial peak strain rate, especially circumferential peak strain rate, which exhibited the highest correlation (r = - 0.756 ~ 0.795).

Conclusions: T2DM exacerbates LV diastolic dysfunction in patients with essential hypertension. The LV filling model changes reflected by the CMR volume-time curve could provide more information for early clinical intervention.
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http://dx.doi.org/10.1186/s12933-021-01262-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993470PMC
March 2021

Distinct placental molecular processes associated with early-onset and late-onset preeclampsia.

Theranostics 2021 5;11(10):5028-5044. Epub 2021 Mar 5.

Center for genetics and Developmental Systems Biology, Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.

Patients with preeclampsia display a spectrum of onset time and severity of clinical presentation, yet the underlying molecular bases for the early-onset and late-onset clinical subtypes are not known. Although several transcriptome studies have been done on placentae from PE patients, only a small number of differentially expressed genes have been identified due to very small sample sizes and no distinguishing of clinical subtypes. We carried out RNA-seq on 65 high-quality placenta samples, including 33 from 30 patients and 32 from 30 control subjects, to search for dysregulated genes and the molecular network and pathways they are involved in. We identified two functionally distinct sets of dysregulated genes in the two major subtypes: 2,977 differentially expressed genes in early-onset severe preeclampsia, which are enriched with metabolism-related pathways, notably transporter functions; and 375 differentially expressed genes in late-onset severe preeclampsia, which are enriched with immune-related pathways. We also identified some key transcription factors, which may drive the widespread gene dysregulation in both early-onset and late-onset patients. These results suggest that early-onset and late-onset severe preeclampsia have different molecular mechanisms, whereas the late-onset mild preeclampsia may have no placenta-specific causal factors. A few regulators may be the key drivers of the dysregulated molecular pathways.
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http://dx.doi.org/10.7150/thno.56141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7978310PMC
March 2021

Preparation of a rice straw-based green separation layer for efficient and persistent oil-in-water emulsion separation.

J Hazard Mater 2021 Mar 8;415:125594. Epub 2021 Mar 8.

Shandong Provincial Key Laboratory of Water Pollution Control and Resource Reuse, School of Environmental Science and Engineering, Shandong University, Jinan 250100, PR China.

Inefficiency, high cost, and complex operation have emerged as shackles for large-scale separate oil-in-water emulsion. Herein, a low-cost and eco-friendly separation layer with a rough structure and rich anionic groups was fabricated from rice straw (RS) via a simple acid-base treatment and slight squeeze process. The separation layer's morphology, composition, and wettability were investigated. It was then employed to separate oil-in-water emulsion. The RS after acid and alkali treatment (AA-RS) exhibited a clear fiber structure and abundant humps, which made the separation layer superwettable and highly electronegative (-26.55 mV). The overlapped and intertwined AA-RS layer structure owned a superior performance for hexadecyl-trimethyl-ammonium-bromide (CTAB) adsorption and tiny oil interception. As a result, the separation layer had stable fluxes (>500 LMH) for multiple CTAB-stabilized emulsions and the obtained filtrates performed low total organic carbon (TOC) contents (<30 mg/L). In addition, the AA-RS layer had excellent renewability (10 cycles/ 200 mL) and the flux could be substantially recovered merely by aqueous wash. Moreover, filtrate analysis showed that the AA-RS layer had a good effect on actual emulsion treatment with a TOC removal rate of 89.56%.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125594DOI Listing
March 2021

Tracking the fate of artificial sweeteners within the coastal waters of Shenzhen city, China: From wastewater treatment plants to sea.

J Hazard Mater 2021 Feb 23;414:125498. Epub 2021 Feb 23.

Analytical, Environmental and Geochemistry (AMGC), Vrije Universiteit Brussel (VUB), 1050, Belgium.

Artificial sweeteners (ASs), as a new emerging pollutant, the fate from wastewater treatment plants (WWTPs) to sea is growing concerned. In this study, the distribution and polluted loading of six typical ASs were analyzed based on the measurement in influent, primary effluent, secondary effluent, tertiary effluent, suspended particulate matter (SPM), and sludge from four WWTPs and receiving waters near the coast of Shenzhen city, China. Elevated levels of ASs were detected in WWTPs located near a highly populated area (about 14,000 people km). Sucralose was predominant in all water samples (0.1-22.2 μg L), and had a 1.6-704.0 times higher concentration than the means of other ASs detected. Aspartame were mainly distributed in SPM and sludge, and the fractions in offshore water exceeded 45%. Acesulfame, sucralose, cyclamate and saccharin could be effectively removed by secondary biochemical treatment. The average daily loading (4.2 g d 1000people) and discharge loading (0.4 g d 1000people) of sucralose in WWTPs was higher than those of the other ASs. Dissolved organic carbon and UV can affect the fate of ASs, and SPM mainly affects the distributions of aspartame and neotame. As a potential sewage indicator, neotame deserves further attention.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125498DOI Listing
February 2021

Schisandrol B promotes liver enlargement via activation of PXR and YAP pathways in mice.

Phytomedicine 2021 Apr 17;84:153520. Epub 2021 Feb 17.

Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China; School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China. Electronic address:

Background: Schisandrol B (SolB) is one of the bioactive components from a traditional Chinese medicine Schisandra chinensis or Schisandra sphenanthera. It has been demonstrated that SolB exerts hepatoprotective effects against drug-induced liver injury and promotes liver regeneration. It was found that SolB can induce hepatomegaly but the involved mechanisms remain unknown.

Purpose: This study aimed to explore the mechanisms involved in SolB-induced hepatomegaly.

Methods: Male C57BL/6 mice were injected intraperitoneally with SolB (100 mg/kg) for 5 days. Serum and liver samples were collected for biochemical and histological analyses. The mechanisms of SolB were investigated by qRT-PCR and western blot analyses, luciferase reporter gene assays and immunofluorescence.

Results: SolB significantly increased hepatocyte size and proliferation, and then promoted liver enlargement without liver injury and inflammation. SolB transactivated human PXR, activated PXR in mice and upregulated hepatic expression of its downstream proteins, such as CYP3A11, CYP2B10 and UGT1A1. SolB also significantly enhanced nuclear translocation of PXR and YAP in human cell lines. YAP signal pathway was activated by SolB in mice.

Conclusion: These findings demonstrated that SolB can significantly induce liver enlargement, which is associated with the activation of PXR and YAP pathways.
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http://dx.doi.org/10.1016/j.phymed.2021.153520DOI Listing
April 2021

Morphological speculation of the MHPD and related clinical projections.

Surg Radiol Anat 2021 Mar 4. Epub 2021 Mar 4.

Department of Hepatobiliary Surgery, General Rocket Hospital of Chinese People's Liberation Army, Beijing, People's Republic of China.

Objective: The concept of mesopancreas has been brought into focus nowadays. Studies on membrane morphology of pancreas are clinically significant in determining an ideal surgical route for a "holy plane". In this paper, we aimed to observe the structure of the peripancreatic membranes and its interactions with adjacent tissues; tentatively put forward the proposition of mesohepatopancreaticoduodenum (MHPD) and explore in depth in surgical local resection.

Methods: 33 cadavers were examined in the experiment, including 30 for gross anatomy and 3 for histological observation after transection. The histological characteristics of the membrane covering the pancreas were proved by Masson and Bielschowsky silver staining and further explored in clinical application and testified in a surgical scenario. All above were carried out through traditional procedures.

Results: The anterior surface membrane of the pancreas was intact and the posterior portion expanding to the pancreaticoduodenum enclosed the surface of the duodenum and the pancreatic head, which could be easily isolated from the posterior abdominal wall. The posterior surface membrane around the body and tail wrapped the pancreatic parenchyma, which created a soft-tissue window for the posterior abdominal wall. Then, dense connective tissue adhesions were detected between the celiac artery and the superior mesenteric artery.

Conclusions: The embryonic origin of the mesopancreas and the surgical procedures were reviewed and inspected based on the proposition of MHPD and above results. We hope that this study could stir up our interest in the advancement of imaging diagnoses and minimally invasive surgical treatment of pancreas.
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http://dx.doi.org/10.1007/s00276-021-02725-6DOI Listing
March 2021

Bloodstream Infections Caused by Carbapenem-Resistant : Risk Factors for Mortality, Antimicrobial Therapy and Treatment Outcomes from a Prospective Multicenter Study.

Infect Drug Resist 2021 24;14:731-742. Epub 2021 Feb 24.

Department of Clinical Microbiology, Peking University People's Hospital, Beijing, People's Republic of China.

Purpose: Carbapenem-resistant bloodstream infections (CRE BSIs) have a high mortality. However, an optimal antimicrobial treatment has not been determined. This study was conducted to evaluate the risk factors for mortality and provided potential therapeutic options for treatment of CRE infection.

Patients And Methods: We investigated patients with CRE BSIs from 18 hospitals across nine Chinese provinces from January to December 2019. Data were collected from the medical records according to a pre-established questionnaire. Antimicrobial susceptibility testing and DNA sequencing were performed to investigate the characteristics of isolates.

Results: A total of 208 patients enrolled; the overall 30-day mortality rate was 46.2%. The causative pathogen was carbapenem-resistant (CRKP) (85.6%). Patients infected by ST11-KL64 CRKP had a high sepsis/septic shock incidence rate (p < 0.05). Sepsis/septic shock, short duration of antimicrobial therapy and empirical using tigecycline were independent risk factors for mortality (p < 0.05 for each risks). Appropriate therapy had better survival benefit than inappropriate therapy (p = 0.003). No difference was identified between monotherapy and combination therapy (p = 0.105). Tigecycline as a frequently used antimicrobial had poor therapeutic effect on BSI patients (p < 0.001). Carbapenem-based treatment had a better therapeutic effect on patients infected by isolates with meropenem MIC ≤ 8 mg/L (p = 0.022). The patients who received short duration of antimicrobial therapy had poorer prognosis (p < 0.001) than the patients who received long duration of antimicrobial therapy.

Conclusion: Reducing the mortality of CRE BSIs need to comprehensively consider whether the antimicrobials were used appropriately, together with infection severity and CRE strains.
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http://dx.doi.org/10.2147/IDR.S294282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917342PMC
February 2021

Exercise-induced muscle damage: multi-parametric MRI quantitative assessment.

BMC Musculoskelet Disord 2021 Mar 2;22(1):239. Epub 2021 Mar 2.

Department of Radiology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Heping District, Shenyang, 110004, China.

Background: To explore the value of magnetic resonance quantitative analysis using diffusion tensor imaging, T2 mapping, and intravoxel incoherent motion in the evaluation of eccentric exercise-induced muscle damage and to compare the effects of various eccentric exercise modes at different time points in rats.

Methods: A total of 174 Sprague-Dawley male rats were randomly divided into five groups: control, once-only exercise, continuous exercise, intermittent exercise, and once-fatigue exercise groups. Each experimental group was divided into seven time-subgroups: 0.5 h, 24 h, 48 h, 72 h, 96 h, 120 h and 168 h after exercise. The quadriceps femoris muscles were then scanned using magnetic resonance imaging. The apparent diffusion coefficient and fractional anisotropy values of diffusion tensor imaging, T2 values of T2 mapping, D and D* values of intravoxel incoherent motion and optical density values of desmin were measured. Associations among different eccentric exercise programmes, magnetic resonance imaging findings, and histopathological results were evaluated. Dunnett's test, two-way repeated measures analysis of variance, and Pearson correlation analysis were used for statistical analysis.

Results: Diffusion tensor imaging showed that the number of muscle fibre bundles decreased to varying degrees with different time points and eccentric exercises. Apparent diffusion coefficient values of the exercise groups showed a trend that first increased and then decreased, the opposite of fractional anisotropy. The specimens in all eccentric exercise programmes showed high signal T2 values after exercise, the highest among which was in the once-fatigue exercise group. D and D* in the experimental groups were significantly higher than those in the control group at 0.5-48 h after exercise. The apparent diffusion coefficient, fractional anisotropy, T2, D and D* values correlated with the optical density values of desmin.

Conclusions: Diffusion tensor imaging, T2 mapping, and intravoxel incoherent motion technology accurately reflect the degree of skeletal muscle damage and recovery associated with eccentric exercise. The degree of muscle damage was the lowest in the continuous exercise group and the highest in the once-fatigue exercise group, which may provide more information and guidance for the formulation of physical and athletic training programmes.
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http://dx.doi.org/10.1186/s12891-021-04085-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927395PMC
March 2021

Versatile 3D reduced graphene oxide/poly(amino-phosphonic acid) aerogel derived from waste acrylic fibers as an efficient adsorbent for water purification.

Sci Total Environ 2021 Feb 19;776:145973. Epub 2021 Feb 19.

Hubei Key Laboratory of Biomass Fibers and Eco-dyeing & Finishing, School of Chemistry and Chemical Engineering, Wuhan Textile University, Wuhan 430073, China; Hubei key Laboratory of Novel Reactor and Green Chemical Technology, National Engineering Research Center of Phosphorus Resource Exploitation, Wuhan Institute of Technology, Wuhan 430074, China. Electronic address:

The fabrication of multifunctional materials to remove soluble heavy metal ions and dyes, as well as insoluble oils from waste water is urgently required, yet remains a daunting challenge because of difficulty in controlling their structure and property to satisfy various demands. Herein, for the first time, novel 3D reduced graphene oxide/poly(amino-phosphonic acid) (PAPA) aerogels (rGO/PAPAs) with different PAPA content were developed by solvothermal reduction of the graphene oxide and cross-linking with PAPA chain, and subsequently employed as versatile adsorbent for the removal of complex pollutants such as Cr(III) ion, methylene blue (MB) dye and various kinds of organic solvents from water. Benefiting from the synergistic effect of the reduced graphene oxide (rGO) sheet and PAPA component, as well as its unique 3D structure, the resultant aerogel (rGO/PAPA-2) gained amphiphilic, ultralight, and multifunctional properties. Thus, it showed a fast adsorption rate (within 15 min) and high adsorption capacity (up to 327.1 mg/g) for Cr(III) ion at an optimal pH of 5.5 due to its unique 3D network structure with abundant amino-phosphonic acid functional groups. The uptake of Cr(III) by rGO/PAPA-2 was fitted well with the Langmuir isotherm and pseudo-second-order kinetic model. The adsorption mechanism of Cr(III) onto rGO/PAPA-2 can be attributed to electrostatic attraction and surface complexation with APA groups. In addition, the rGO/PAPA-2 displayed an excellent adsorption performance for MB (694.5 mg/g) and several organic solvents (83.2 to 254.3 g/g). Moreover, the rGO/PAPA-2 exhibited a good regeneration (around 99%) and satisfactory recovery abilities for the tested adsorbates. Notably, PAPA chains can be easily prepared from waste acrylic fibers, making it become a cost effective but versatile candidate to prepare new material. Therefore, this work provides a new design strategy to fabricate the rGO/PAPA-2 aerogel with great prospect for sophisticated industrial wastewater cleanup.
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http://dx.doi.org/10.1016/j.scitotenv.2021.145973DOI Listing
February 2021

Association of a Safety Program for Improving Antibiotic Use With Antibiotic Use and Hospital-Onset Clostridioides difficile Infection Rates Among US Hospitals.

JAMA Netw Open 2021 02 1;4(2):e210235. Epub 2021 Feb 1.

Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Importance: Regulatory agencies and professional organizations recommend antibiotic stewardship programs (ASPs) in US hospitals. The optimal approach to establish robust, sustainable ASPs across diverse hospitals is unknown.

Objective: To assess whether the Agency for Healthcare Research and Quality Safety Program for Improving Antibiotic Use is associated with reductions in antibiotic use across US hospitals.

Design, Setting, And Participants: A pragmatic quality improvement program was conducted and evaluated over a 1-year period in US hospitals. A total of 437 hospitals were enrolled. The study was conducted from December 1, 2017, to November 30, 2018. Data analysis was performed from March 1 to October 31, 2019.

Interventions: The Safety Program assisted hospitals with establishing ASPs and worked with frontline clinicians to improve their antibiotic decision-making. All clinical staff (eg, clinicians, pharmacists, and nurses) were encouraged to participate. Seventeen webinars occurred over 12 months, accompanied by additional durable educational content. Topics focused on establishing ASPs, the science of safety, improving teamwork and communication, and best practices for the diagnosis and management of infectious processes.

Main Outcomes And Measures: The primary outcome was overall antibiotic use (days of antibiotic therapy [DOT] per 1000 patient days [PD]) comparing the beginning (January-February 2018) and end (November-December 2018) of the Safety Program. Data analysis occurred using linear mixed models with random hospital unit effects. Antibiotic use from 614 hospitals in the Premier Healthcare Database from the same period was analyzed to evaluate contemporary US antibiotic trends. Quarterly hospital-onset Clostridioides difficile laboratory-identified events per 10 000 PD were a secondary outcome.

Results: Of the 437 hospitals enrolled, 402 (92%) remained in the program until its completion, including 28 (7%) academic medical centers, 122 (30%) midlevel teaching hospitals, 167 (42%) community hospitals, and 85 (21%) critical access hospitals. Adherence to key components of ASPs (ie, interventions before and after prescription of antibiotics, availability of local antibiotic guidelines, ASP leads with dedicated salary support, and quarterly reporting of antibiotic use) improved from 8% to 74% over the 1-year period (P < .01). Antibiotic use decreased by 30.3 DOT per 1000 PD (95% CI, -52.6 to -8.0 DOT; P = .008). Similar changes in antibiotic use were not observed in the Premier Healthcare Database. The incidence rate of hospital-onset C difficile laboratory-identified events decreased by 19.5% (95% CI, -33.5% to -2.4%; P = .03).

Conclusions And Relevance: The Agency for Healthcare Research and Quality Safety Program appeared to enable diverse hospitals to establish ASPs and teach frontline clinicians to self-steward their antibiotic use. Safety Program content is publicly available.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.0235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910818PMC
February 2021

Flotillin-1 Interacts With and Sustains the Surface Levels of TRPV2 Channel.

Front Cell Dev Biol 2021 9;9:634160. Epub 2021 Feb 9.

State Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan, China.

Transient receptor potential vanilloid subtype 2 (TRPV2) channel is a polymodal receptor regulating neuronal development, cardiac function, immunity and oncogenesis. The activity of TRPV2 is regulated by the molecular interactions in the subplasmalemmel signaling complex. Here by yeast two-hybrid screening of a cDNA library of mouse dorsal root ganglia (DRG) and patch clamp electrophysiology, we identified that flotillin-1, the lipid raft-associated protein, interacts with TRPV2 channel and regulates its function. The interaction between TRPV2 and flotillin-1 was validated through co-immuoprecipitation using endogenous DRG neurons and the recombinant expression model in HEK 293T cells. Fluorescent imaging and bimolecular fluorescence complementation (BiFC) further revealed that flotillin-1 and TRPV2 formed a functional complex on the cell membrane. The presence of flotillin-1 enhanced the whole-cell current density of TRPV2 via increasing its surface expression levels. Using site-specific mapping, we also uncovered that the SPFH (stomatin, prohibitin, flotillin, and HflK/C) domain of flotillin-1 interacted with TRPV2 N-termini and transmembrane domains 1-4, respectively. Our findings therefore demonstrate that flotillin-1 is a key element in TRPV2 signaling complex and modulates its cellular response.
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http://dx.doi.org/10.3389/fcell.2021.634160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900159PMC
February 2021

Prognostic Roles of N6-Methyladenosine METTL3 in Different Cancers: A System Review and Meta-Analysis.

Cancer Control 2021 Jan-Dec;28:1073274821997455

Department of Urology, 12579Southeast University Affiliated Zhongda Hospital, Nanjing, Jiangsu, China.

Background: Recent studies have shown that methyltransferase-like 3, a catalytic enzyme that is predominant in the N6-methyladenosine methyltransferase system, is abnormally expressed in various types of carcinoma and is correlated with poorer prognosis. However, the clinical functions of methyltransferase-like 3 in the prognosis of tumors are not fully understood.

Methods: We identified studies by searching PubMed, Web of Science, and MedRvix for literature (up to June 30, 2020), and collected a total of 9 studies with 1257 patients for this meta-analysis. The cancer types included gastric cancer, breast cancer, non-small cell lung cancer, bladder cancer, colorectal cancer and ovarian. We further used The Cancer Genome Atlas dataset to validate the results.

Results: High methyltransferase-like 3 expression clearly predicted a worse outcome (high vs. low methyltransferase-like 3 expression group; hazard ratio = 2.09, 95% confidence interval 1.53-2.89, = 0.0001). Moreover, methyltransferase-like 3 expression was associated with differentiation (moderate + poor vs. well, pooled odds ratio = 1.76, 95% confidence interval 1.32-2.35, = 0.0001), and gender (male vs. female, pooled odds ratio = 0.73, 95% confidence interval 0.55-0.97, = 0.029).

Conclusion: Our results suggest that methyltransferase-like 3 upregulation is significantly associated with poor prognosis and could potentially function as a tumor biomarker in cancer prognosis.
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http://dx.doi.org/10.1177/1073274821997455DOI Listing
February 2021

High Prevalence of Triple-Negative Breast Cancer in Southern Shaanxi Province, China.

Cancer Manag Res 2021 17;13:1609-1615. Epub 2021 Feb 17.

Department of Clinical Laboratory, 3201 Hospital, Xi'an Jiaotong University Health Science Center, Hanzhong, Shaanxi, 723000, People's Republic of China.

Purpose: Describing the clinical features of patients with breast cancer in an area is important to provide the information for the local oncologist to make sound treatment plans. In this study, we explored the clinical features of breast cancer patients in Southern Shaanxi Province, China.

Patients And Methods: A total of 328 breast cancer patients between 2010 and 2015 were recruited at our hospital. Patients' clinical information and the results of the histopathological examination were collected. Independent sample -test and Cox regression were used to analyze the data.

Results: The peak age onset of these patients was between 45 and 50. At diagnosis, 8.23% of patients were at clinical stage 1 and 29.57% were triple-negative breast cancer subtype. High expression of Ki-67 in these patients was found associated with triple-negative breast cancer. The 5-year survival rate in these patients was 66.4%, and the survival rate in stage 1 and 2 patients (88.2%) was significantly higher than that in stage 3 and4 (57.4%).

Conclusion: We here reported the clinical features of patients with breast cancer in Southern Shaanxi Province, China. The breast cancer patients in Southern Shaanxi Province showed a unique clinical feature.
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http://dx.doi.org/10.2147/CMAR.S295085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898196PMC
February 2021

High-efficiency, flexibility and lead-free X-ray shielding multilayered polymer composites: layered structure design and shielding mechanism.

Sci Rep 2021 Feb 23;11(1):4384. Epub 2021 Feb 23.

The State Key Laboratory of Polymer Materials Engineering, Polymer Research Institute of Sichuan University, Chengdu, 610065, China.

To overcome the severe toxicity and blind absorption zone of conventional lead-based shielding materials for X-rays in the 70-90 keV range, the lead-free multilayered polymer composites were designed and fabricated. The effects of the direction of incidence of the X-rays and number of layers as well as layer thickness ratio of the (tungsten/ethylene-octene copolymer)/(bismuth/ethylene-octene copolymer) layered composites on their shielding efficiency were studied systematically. Compared to the traditional polymer blending, the multilayered polymer composites exhibited the improved photon attenuation. The multilayered polymer composites (layer thickness ratio was 3:7) with 6 layers had the best X-ray shielding ability. Moreover, the X-ray shielding provided by the multi-layered interfaces and the multiple complementary effect of the absorption within the multilayered structure were firstly proposed based on computer simulations. The multilayered structural design effectively weakened the probability of the X-ray penetration. Therefore, the X-ray shielding capability can be effectively enhanced through increasing number of layers and the synergistic effect of multi-layered interfaces. The experimental results of this study can serve as guidelines for the fabrication of flexibility, lead-free, lightweight and high-efficiency X-ray shielding materials.
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http://dx.doi.org/10.1038/s41598-021-83031-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902636PMC
February 2021

Research progress in the pathogenic mechanisms and imaging of severe frostbite.

Eur J Radiol 2021 Apr 17;137:109605. Epub 2021 Feb 17.

Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, China. Electronic address:

Purpose: This article reviews the pathological mechanisms and progress of imaging of severe frostbite to assist in the search for targets for clinical diagnosis and treatment of severe frostbite. This review also aims to provide strong evidence for clinical diagnosis and treatment of deep frostbite.

Methods: The review was based on the summary and analysis of the existing literature, and explored the pathological mechanism of deep frostbite and the advantages and disadvantages of imaging diagnostic methods.

Results: According to the depth of tissue involvement, frostbite is divided into 4 levels. Severe frostbite includes Grade 3 and Grade 4 frostbite. Clinical performance evaluation and imaging diagnostic research have always been the mainstream of severe frostbite diagnosis. Imaging methods focus on vascular patency and tissue vitality. This article introduces angiography, SETCT/CT and MRA, and we summarize the advantages and disadvantages of these imaging methods. We recommend corresponding imaging modalities according to the state of frostbite patients.

Conclusions: Imaging examination, especially angiography and bone scans, provide useful information for determining the diagnosis and prognosis of severe frostbite. In order to obtain a good clinical prognosis, clinicians should first perform SPECT/CT. MRA does not burden the patient's body, but the balance between cost and benefit must be considered. Angiography provides a good feedback on the changes in blood vessel status before and after treatment, which is helpful for discovering the response of limbs to treatment.
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http://dx.doi.org/10.1016/j.ejrad.2021.109605DOI Listing
April 2021

A novel micropropagation of Lycium ruthenicum and epigenetic fidelity assessment of three types of micropropagated plants in vitro and ex vitro.

PLoS One 2021 23;16(2):e0247666. Epub 2021 Feb 23.

Key Laboratory of Forest Tree Genetics, Breeding and Cultivation of Liaoning Province, College of Forestry, Shenyang Agricultural University, Shenyang, Liaoning, China.

Lycium ruthenicum is an excellent eco-economic shrub. Numerous researches have been conducted for the function of its fruits but scarcely focused on the somaclonal variation and DNA methylation. An efficient micropropagation protocol from leaves and stems of L. ruthenicum was developed in this study, in which not only the leaf explants but also the stem explants of L. ruthenicum were dedifferentiated and produced adventitious buds/multiple shoots on one type of medium. Notably, the efficient indirect organogenesis of stem explants was independent of exogenous auxin, which is contrary to the common conclusion that induction and proliferation of calli is dependent on exogenous auxin. We proposed that sucrose supply might be the crucial regulator of stem callus induction and proliferation of L. ruthenicum. Furthermore, results of methylation-sensitive amplified polymorphism (MSAP) showed that DNA methylation somaclonal variation (MSV) of CNG decreased but that of CG increased after acclimatization. Three types of micropropagated plants (from leaf calli, stem calli and axillary buds) were epigenetically diverged more from each other after acclimatization and the ex vitro micropropagated plants should be selected to determine the fidelity. In summary, plants micropropagated from axillary buds and leaves of L. ruthenicum was more fidelity and might be suitable for preservation and propagation of elite germplasm. Also, leaf explants should be used in transformation. Meanwhile, plants from stem calli showed the highest MSV and might be used in somaclonal variation breeding. Moreover, one MSV hotspot was found based on biological replicates. The study not only provided foundations for molecular breeding, somaclonal variation breeding, preservation and propagation of elite germplasm, but also offered clues for further revealing novel mechanisms of both stem-explant dedifferentiation and MSV of L. ruthenicum.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247666PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901770PMC
February 2021

Analysis of Differentially Expressed Genes of Chrysoperla sinica Related to Flight Capacity by Transcriptome.

J Insect Sci 2021 Jan;21(1)

College of Plant Protection, Shanxi Agricultural University, Taiyuan, P.R. China.

The lacewing Chrysoperla sinica (Tjeder) is a common natural enemy of many insect pests in China and is frequently employed for biological control programs. Adults make migratory flights after emergence, which reduces their effectiveness as biological control agents. Previously, we proved that 2-d-old unmated females exhibited significantly stronger flight ability than 3-d-old ones. Meanwhile, 3-d-old unmated adults flew significantly longer distances than mated ones. In this study, Illumina RNA sequencing was performed to characterize differentially expressed genes (DEGs) between virgin and mated adults of different ages in a single female strain of C. sinica. In total, 713,563,726 clean reads were obtained and de novo assembled into 109,165 unigenes with an average length of 847 bp (N50 of 1,754 bp), among which 4,382 (4.01%) unigenes matched known proteins. Based on these annotations, many putative transcripts were related to C. sinica's flight capacity and muscle structure, energy supply, growth, development, environmental adaptability, and metabolism of nutritional components and bioactive components. In addition, the differential expression of transcripts between different ages and mating status were analyzed, and DEGs participating in flight capacity and muscles were detected, including glutathione hydrolase, NAD-specific glutamate dehydrogenase, aminopeptidase, and acidic amino acid decarboxylase. The DEGs with functions associated with flight capacity and muscles exhibited higher transcript levels for younger (2 d--old) virgins. This comprehensive C. sinica transcriptomic data provide a foundation for a better understanding of the molecular mechanisms underlying the flight capacity to meet the physiological demands of flight muscles in C. sinica.
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http://dx.doi.org/10.1093/jisesa/ieab003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901589PMC
January 2021

CD44-targeted pH-responsive micelles for enhanced cellular internalization and intracellular on-demand release of doxorubicin.

Artif Cells Nanomed Biotechnol 2021 Dec;49(1):173-184

Suzhou Polytechnic Institute of Agriculture, Suzhou, China.

Poor cellular uptake and slow intracellular drug release remain the main barriers for the efficient application of micellar delivery system. Taking advantage of the overexpressed CD44 receptor and mild acidic microenvironment of tumour cells, CD44-targeted pH-responsive micelles based on the self-assembly of histidine-hyaluronic acid-dodecylamine (His-HA-DA) were prepared for the delivery of doxorubicin (DOX). These micelles exhibited pH-responsive behaviour with increased particle size, decreased encapsulation efficiency (EE%) of DOX and rapid release of DOX triggered by low pH. Compared with free DOX, DOX/HHD exhibited relatively high cellular uptake mainly the CD44-mediated endocytosis. The on-demand intracellular release of DOX from DOX/HHD led to improved cytotoxicity. DOX/HHD also showed great penetration efficiency in 3D tumour spheres . Moreover, these micelles with suitable particle size gained excellent tumour-targeting effects, as well as improved anti-tumour effects and reduced side effects . In conclusion, these micelles with CD44 targeted and pH-responsive behaviours provide a promising strategy for the efficient delivery of anti-tumour drugs .
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http://dx.doi.org/10.1080/21691401.2021.1884085DOI Listing
December 2021