Publications by authors named "Jun Hu"

1,531 Publications

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MFG-E8 Knockout Aggravated Nonalcoholic Steatohepatitis by Promoting the Activation of TLR4/NF-B Signaling in Mice.

Mediators Inflamm 2022 20;2022:5791915. Epub 2022 Jun 20.

Department of Anatomy, Chongqing Medical University, Chongqing, China.

Nonalcoholic steatohepatitis (NASH) is the common liver disease characterized by hepatic steatosis, inflammation, and fibrosis; there are no approved drugs to treat this disease because of incomplete understanding of pathophysiological mechanisms of NASH. Milk fat globule-epidermal growth factor-factor 8 (MFG-E8), a multifunctional glycoprotein, has shown anti-inflammation and antifibrosis. Here, MFG-E8 was shown to play a key role in NASH progression. Using methionine and choline deficient (MCD) diet-fed mice, we found MFG-E8 knockout exacerbated hepatic damage and steatosis as indicated by increased plasma transaminases activities and hepatic histopathologic change, higher hepatic triglycerides (TGs), and lipid accumulation. Moreover, liver fibrosis and inflammation elicited by MCD were aggravated in MFG-E8 knockout mice. Mechanistically, MFG-E8 knockout facilitated activation of hepatic toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-B) signaling pathway in MCD-fed mice. experiment, the TLR4 specific antagonist TAK-242 rescued palmitic acid- (PA-) primed lipid formation and inflammation in MFG-E8 knockout primary murine hepatocytes. These findings indicated that MFG-E8 is involved in the progression of NASH and the possible mechanism by which MFG-E8 knockout exacerbated NASH in mice is associated with activation of the TLR4/NF-B signaling pathway.
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http://dx.doi.org/10.1155/2022/5791915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9236848PMC
July 2022

Room-Temperature Photooxidation of CH to CHOH with Nearly 100% Selectivity over Hetero-ZnO/FeO Porous Nanosheets.

J Am Chem Soc 2022 Jun 28. Epub 2022 Jun 28.

Hefei National Research Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei 230026, China.

The huge challenge for CH photooxidation into CHOH lies in the activation of the inert C-H bond and the inhibition of CHOH overoxidation. Herein, we design two-dimensional in-plane -scheme heterostructures composed of two different metal oxides, with efforts to polarize the symmetrical CH molecules and strengthen the O-H bond in CHOH. As a prototype, we first fabricate ZnO/FeO porous nanosheets, where high-resolution transmission electron microscopy and X-ray photoelectron spectroscopy affirm their in-plane -scheme heterostructure. Fourier transform infrared spectra and electron paramagnetic resonance spectra demonstrate their higher amount of ·CH radicals relative to the pristine ZnO porous nanosheets, in which density functional theory calculations validate that the high local charge accumulation on Fe sites lowers the CH adsorption energy from 0.14 to 0.06 eV. Moreover, the charge-accumulated Fe sites strengthen the polarity of the O-H bond in CHOH through transferring electrons to the O atoms, confirmed by the increased barrier from 0.30 to 2.63 eV for *CHO formation, which inhibits the homolytic O-H bond cleavage and thus suppresses CHOH overoxidation. Accordingly, the CHOH selectivity over ZnO/FeO porous nanosheets reaches up to nearly 100% with an activity of 178.3 μmol g, outperforming previously reported photocatalysts without adding any oxidants under room temperature and ambient pressure.
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http://dx.doi.org/10.1021/jacs.2c03866DOI Listing
June 2022

Biomolecular Regulation of Zinc Deposition to Achieve Ultra-Long Life and High-Rate Zn Metal Anodes.

Small 2022 Jun 24:e2202509. Epub 2022 Jun 24.

School of Advanced Materials, Peking University Shenzhen Graduate School, Shenzhen, 518055, China.

Aqueous zinc-ion batteries (ZIBs) have been extensively studied due to their inherent safety and high energy density for large-scale energy storage. However, the practical application is significantly limited by the growing Zn dendrites on metallic Zn anode during cycling. Herein, an environmental biomolecular electrolyte additive, fibroin (FI), is proposed to guide the homogeneous Zn deposition and stabilize Zn anode. This work demonstrates that the FI molecules with abundant electron-rich groups (NH, OH, and CO) can anchor on Zn anode surface to provide more nucleation sites and suppress the side reactions, and the strong interaction with water molecules can simultaneously regulate the Zn coordination environment facilitating the uniform deposition of Zn. As a consequence, only 0.5 wt% FI additive enables a highly reversible Zn plating/stripping over 4000 h at 1 mA cm , indicating a sufficient advance in performance over state-of-the-art Zn anodes. Furthermore, when applied to a full battery (NaVO/Zn), the cell exhibits excellent capacity retention of 98.4% after 1000 cycles as well as high Coulombic efficiency of 99%, whereas the cell only operates for 68 cycles without FI additive. This work offers a non-toxic, low-cost, effective additive strategy to solve dendrites problems and achieve long-life and high-performance rechargeable aqueous ZIBs.
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http://dx.doi.org/10.1002/smll.202202509DOI Listing
June 2022

LncRNA DLEU2 silencing impedes the migration, invasion and EMT in gastric cancer cell by suppressing PI3K/AKT signaling pathway.

Immunopharmacol Immunotoxicol 2022 Jun 23:1-13. Epub 2022 Jun 23.

Oncology Department, Gaochun People's Hospital, Nanjing City, China.

The high expression of long non-coding RNA deleted in lymphocytic leukaemia 2 (lncRNA DLEU2) has been confirmed in gastric cancer (GC). However, the detailed mechanism concerning its involvement in GC remained unclear, which we aimed to explore in this study. LncRNA DLEU2 expression in GC was estimated by bioinformatic analysis, and the relationship between the expression of DLEU2 and the clinicopathological characteristics of patients with GC was performed. qRT-PCR was employed to detect the expression of lncRNA DLEU2 and confirm the transfection efficiency following the knockdown or overexpression of DLEU2. Functional assays, including CCK-8, flow cytometry, scratching test and Transwell assays, were used to determine the role of DLEU2 in tumor phenotypes. The effects of DLEU2 on the PI3K/Akt pathway were detected by western blot. For elucidating the functions of DLEU2/PI3K/Akt axis in GC, we inhibited the PI3K/Akt pathway in rescue experiments, and evaluated the expression levels of epithelial-mesenchymal transition (EMT)-related proteins by western blot. The expression of DLEU2 was aberrantly up-regulated in GC tissues and cells, which was correlated with the degree of tumor differentiation, cancer antigen 19-9 (CA19-9) and Lauren histologic classification of patients with GC. Silencing of DLEU2 induced apoptosis, attenuated viability, migration and invasion as well as inhibited the PI3K/Akt signaling pathway in GC cells. Mechanistically, the DLEU2/PI3K/Akt axis promoted the progression of GC and the EMT by down-regulating the expression of E-Cadherin and up-regulating those of N-Cadherin and Vimentin. LncRNA DLEU2 promoted the migration, invasion and EMT in GC by activating the PI3K/Akt pathway.
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http://dx.doi.org/10.1080/08923973.2022.2078727DOI Listing
June 2022

A Dielectric Polymer/Metal Oxide Nanowire Composite for Self-Adaptive Charge Release.

Nano Lett 2022 Jun 22. Epub 2022 Jun 22.

State Key Laboratory of Power System, Department of Electrical Engineering, Tsinghua University, Beijing, 100084, China.

Electrostatic discharge is a fatal threat to a variety of electronic products. Here we report on a polymer nanocomposite composed of a dielectric polymer embedded with aligned core-shell structured nanowires for highly efficient distributed electrostatic discharge protection. The dielectric nanocomposite is capable of self-adaptive charge release, stemming from the nonlinear interface built in the Bi/Co oxide coated ZnO nanowires that leads to a "hand-in-hand" double-Schottky barrier. The ultralow filler concentration (e.g., 0.5 vol %) endows the nanocomposite with low permittivity (close to the pristine polymer matrix) and high optical transmittance (75%) in the visible light wavelength range, which is desirable in packaging materials and display coatings for portable electronics. The effectiveness for electrostatic discharge protection was validated with an organic light-emitting diode screen protected by the nanocomposite that survived multiple rounds of electrostatic discharge.
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http://dx.doi.org/10.1021/acs.nanolett.2c00887DOI Listing
June 2022

Formation of Bulk Nanobubbles Induced by Accelerated Electrons Irradiation: Dependences on Dose Rates and Doses of Irradiation.

Langmuir 2022 Jun 21. Epub 2022 Jun 21.

Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, 201800, China.

Radiation on aqueous solutions can induce water radiolysis with products of radicals, H, HO, and so on, and their consequent biological effects have long been interested in radiation chemistry. Unlike the decomposition of water by electric current that produces a significant number of bubbles, the gas products from the radiolysis of water are normally invisible by bare eyes, little is known on whether nanosized bubbles can be produced and what their dynamics are upon irradiation. Here, we first presented the formation of nanoscale bulk bubbles by irradiating pure water with accelerated electrons and their concentration and size distribution changes with the dose and rate of irradiation. The nanoparticle tracking analysis showed that irradiation can actually produce a certain amount of bulk nanobubbles in pure water. They exhibited a dependence on the irradiation dose rates and irradiation doses. The results indicated that the concentration of formed bulk nanobubbles increased as the irradiation dose rates increased, but it will increase and then decrease with the increased irradiation doses. The formed bulk nanobubbles could maintain stability for several hours. Our findings will provide a new angle of view for the radiation chemistry of water, and the formed nanobubbles may help elucidate the biological effects of irradiated solutions.
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http://dx.doi.org/10.1021/acs.langmuir.2c00515DOI Listing
June 2022

Iron phosphate hydroxide hydrate as a novel anode material for advanced aqueous full potassium-ion batteries.

Chem Commun (Camb) 2022 Jun 21. Epub 2022 Jun 21.

School of Advanced Materials, Peking University Shenzhen Graduate School, Shenzhen 518055, P. R. China.

The development of aqueous potassium-ion batteries is limited by the lack of suitable anode materials. Here, a novel anode material, iron phosphate hydroxide hydrate FePO(OH)(HO), was introduced and synthesized, which delivers considerable reversible capacities of 80 mA h g at 0.05 A g. An aqueous full potassium-ion battery assembled with the KZn(Fe(CN)) cathode exhibits 80% capacity retention after 1000 cycles.
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http://dx.doi.org/10.1039/d2cc01798aDOI Listing
June 2022

Formation of halonitromethanes from methylamine in the presence of bromide during UV/Cl disinfection.

J Environ Sci (China) 2022 Jul 4;117:28-36. Epub 2022 Jan 4.

Department of Municipal Engineering, Southeast University, Nanjing 211189, China; Research Center for Eco-Environmental Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing 100085, China; Zhejiang Truelove Blanket Technology Co., Ltd., Jinhua 322000, China; College of Environment, Zhejiang University of Technology, Hangzhou 310014, China. Electronic address:

The UV/Cl process is commonly used to achieve a multiple-barrier disinfection and maintain residuals. The study chose methylamine as a precursor to study the formation of high-toxic halonitromethanes (HNMs) in the presence of bromide ions (Br) during UV/Cl disinfection. The maximum yield of HNMs increased first and then decreased with increasing concentration of Br. An excessively high concentration of Br induced the maximum yield of HNMs in advance. The maximum bromine incorporation factor (BIF) increased, while the maximum bromine utilization factor (BUF) decreased with the increase of Br concentration. The maximum yield of HNMs decreased as pH value increased from 6.0 to 8.0 due to the deprotonation process. The BUF value remained relatively higher under an acidic condition, while pH value had no evident influence on the BIF value. The maximum yield of HNMs and value of BUF maximized at a Cl:Br ratio of 12.5, whereas the BIF value remained relatively higher at low Cl:Br ratios (2.5 and 5). The amino group in methylamine was first halogenated, and then released into solution as inorganic nitrogen by the rupture of C-N bond or transformed to nitro group by oxidation and elimination pathways. The maximum yield of HNMs in real waters was higher than that in pure water due to the high content of dissolved organic carbon. Two real waters were sampled to verify the law of HNMs formation. This study helps to understand the HNMs formation (especially brominated species) when the UV/Cl process is adopted as a disinfection technique.
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http://dx.doi.org/10.1016/j.jes.2021.12.031DOI Listing
July 2022

Interfacial Micropancakes: Gas or Contaminations?

Langmuir 2022 Jun 17. Epub 2022 Jun 17.

Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China.

Micropancake, a flat domain with micrometer-scale lateral size and a few nanometer thickness, is usually accompanied by the generation of interfacial nanobubbles at the liquid/solid surfaces. Unlike the nanobubbles, micropancakes are difficult to be produced efficiently, impeding further investigations of their mysterious properties. Very recently, An et al. even argued that the previously observed micropancakes were most likely the contaminate, not the gas layers. Herein, to reveal the nature of micropancakes with solid evidence, we presented the characterization of micropancakes at a highly oriented pyrolytic graphite (HOPG) surface produced by the ethanol-water exchange or gas-supersaturated water. By washing with deeply degassed water (DW), the dissolution of those micropancakes was clearly observed, indicating that they may very well be composed of gas. In addition, the analysis of the force measurements showed the intrinsic differences between those gaseous micropancakes and the insoluble organic films. The data and results supported the interpretation that the real existence of gas micropancakes at liquid/solid surfaces.
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http://dx.doi.org/10.1021/acs.langmuir.2c00390DOI Listing
June 2022

Safety and Efficacy of Sintilimab and Anlotinib as First Line Treatment for Advanced Hepatocellular Carcinoma (KEEP-G04): A Single-Arm Phase 2 Study.

Front Oncol 2022 31;12:909035. Epub 2022 May 31.

Department of Oncology, Jiangsu Province Hospital, The First Affiliated Hospital, Nanjing Medical University, Nanjing, China.

Purpose: Immune checkpoint inhibitors plus antiangiogenic tyrosine kinase inhibitors may offer a first-line treatment for advanced hepatocellular carcinoma (HCC). In this phase 2 trial [registered with clinicaltrials.gov (NCT04052152)], we investigated the safety and efficacy of first-line anti-PD-1 antibody sintilimab plus antiangiogenic TKI anlotinib for advanced HCC.

Methods And Materials: Pathologically-proven advanced HCC patients received sintilimab (200 mg) on day 1 and anlotinib (12 mg) once daily on days 1 to 14 every 3 weeks, with a safety run-in for the first six participants to assess dose-limiting toxicities (DLTs). The primary endpoints were safety and objective response rate (ORR) per RECIST v1.1.

Results: Twenty advanced HCC patients were enrolled. No DLTs occurred in the safety run-in. All patients had treatment-related adverse events (TRAEs). Grade 3 TRAEs occurred in 8 (40.0%) patients, the most common being decreased platelet count (10.0%) and increased γ-glutamyl transferase (10.0%). No grade 4/5 TRAEs occurred. Five (25%) patients developed immune-related AEs. The ORR was 35.0% (95%CI 15.4%-59.2%) per RECIST v1.1 and 55.0% (95%CI 31.5%-76.9%) per modified RECIST. At data cutoff (March 31, 2021), the median progression-free survival was 12.2 months (95%CI, 3.8 to not reached). The median PFS was significantly longer in patients with lower LDH levels (not reached [NR], 95% CI, 8.7 to NR vs. higher LDH levels 5.2 months, 95% CI 3.4 to NR; =0.020) and a CONUT score ≤2 (NR, 95% CI 5.1 to NR vs. CONUT score >2 6.2 months, 95% CI 1.8 to NR; =0.020). Furthermore, patients showing tumor response had a significantly higher median proportion of CD16CD56 NK cells than patients who had stable or progressive disease (21.6% vs. 14.6%; P=0.026).

Conclusion: Sintilimab plus anlotinib showed promising clinical activities with manageable toxicity as first-line treatment of advanced HCC.
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http://dx.doi.org/10.3389/fonc.2022.909035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9197581PMC
May 2022

JAK2 gene knockout inhibits corneal allograft rejection in mice by regulating dendritic cell-induced T cell immune tolerance.

Cell Death Discov 2022 Jun 16;8(1):289. Epub 2022 Jun 16.

Aier Eye Hospital of Wuhan University, Wuhan, 430063, P. R. China.

Corneal allograft rejection can be seen in some patients after corneal transplantation. The present study intends to investigate whether JAK2 gene knockout affects corneal allograft rejection through regulation of dendritic cells (DCs)-induced T cell immune tolerance. In order to identify the target gene related to corneal allograft rejection, high-throughput mRNA sequencing and bioinformatics analysis were performed. JAK2 knockout mice were constructed and subjected to corneal allograft transplantation. The incidence of immune rejection was observed, the percentage of CD4 T cells was detected, and the expression of Th1 cytokine interferon γ (IFN-γ) was determined. Flow cytometry and ELISA were performed to analyze the effects of JAK2 gene knockout on bone marrow-derived DCs (BMDCs). JAK2 was the target gene related to corneal allograft rejection. JAK2 gene knockout contributed to significantly prolonged survival time of corneal grafts in mice and inhibited corneal allograft rejection. The in vitro cell experiment further confirmed that JAK2 gene knockout contributed to the inactivation of CD4 T cells and induced IFN-γ expression, accompanied by inhibition of DC immune function, development, maturation, and secretion of inflammatory cytokines. Collectively, JAK2 gene knockout inactivates CD4 T cells to decrease IFN-γ expression, as well as inhibits DC development, maturation, and secretion of inflammatory cytokines, thereby reducing corneal allograft rejection.
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http://dx.doi.org/10.1038/s41420-022-01067-5DOI Listing
June 2022

Characteristics of Plantar Pressure Distribution in Diabetes with or without Diabetic Peripheral Neuropathy and Peripheral Arterial Disease.

J Healthc Eng 2022 6;2022:2437831. Epub 2022 Jun 6.

College of Mechanical Engineering, Tianjin University of Science and Technology, Tianjin 300222, China.

Background: Excessive plantar pressure leads to increased risk of diabetic foot ulcers. Diabetic peripheral neuropathy (DPN) and peripheral arterial disease (PAD) have been considered to be associated with alterations in gait and plantar pressure in diabetic patients. However, few studies have differentiated the effects with each of them.

Objective: To investigate the plantar pressure distribution in diabetic patients, with DPN and PAD as independent or combined factors.

Methods: 112 subjects were recruited: 24 diabetic patients with both DPN and PAD (DPN-PAD group), 12 diabetic patients with DPN without PAD (DPN group), 10 diabetic patients with PAD without DPN (PAD group), 23 diabetic patients without DPN or PAD, and 43 nondiabetic healthy controls (HC group). The in-shoe plantar pressure during natural walking was measured. Differences in peak pressure, contact area, proportion of high pressure area (%HP), and anterior/posterior position of centre of pressure (COP) were analysed.

Results: Compared with HC group, in DPN-PAD group and DPN group, the peak pressures in all three forefoot regions increased significantly; in PAD group, the peak pressure in lateral forefoot increased significantly. The contact area of midfoot in the DPN-PAD group decreased significantly. PAD group had larger HP% of lateral forefoot, DPN group had larger HP% of inner forefoot, and DPN-PAD group had larger HP% of total plantar area. There was a significant tendency of the anterior displacement of COP in the DPN-PAD group and DPN group. No significant differences were observed between the D group and HC group.

Conclusion: DPN or PAD could affect the plantar pressure distribution in diabetic patients independently or synergistically, resulting in increased forefoot pressure and the area at risk of ulcers. DPN has a more pronounced effect on peak pressure than PAD. The synergistic effect of them could significantly reduce the plantar contact area of midfoot.
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http://dx.doi.org/10.1155/2022/2437831DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9192305PMC
June 2022

Bimodal Treatment of Hepatocellular Carcinoma by Targeted Minimally Interventional Photodynamic/Chemotherapy Using Glyco-Covalent-Organic Frameworks-Guided Porphyrin/Sorafenib.

Acta Biomater 2022 Jun 11. Epub 2022 Jun 11.

Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China. Electronic address:

Very limited treatment options are available to fight hepatocellular carcinoma (HCC), a serious global health concern with high morbidity and mortality. The integration of multiple therapies into one nanoplatform to exert synergistic therapeutic effects offers advantages over monotherapies. Here, we describe the construction of the nanoplatform [email protected] for synergistic chemotherapy and photodynamic therapy (PDT) for HCC using a porphyrin-based covalent organic framework (COF-366) coated with N-acetyl-galactosamine (GalNAc) and rhodamine B (RhB), and loaded with the first-line agent, Sorafenib (Sor). The nanoplatform is targeted towards ASGPR-overexpressed HCC cells and liver tissues by GalNAc and observed by real-time imaging of RhB in vitro and in vivo. The nanoplatform [email protected] exerts an enhanced synergistic tumor suppression effect in a subcutaneous HCC mouse model with a tumor inhibition rate (TGI) of 97% while significantly prolonging survival at very low toxicity. The potent synergistic therapeutic outcome is confirmed in an orthotopic mouse model of HCC with the TGI of 98% with a minimally invasive interventional PDT (IPDT). [email protected] is a promising candidate to be combined with chemo-IPDT for the treatment of HCC. STATEMENT OF SIGNIFICANCE: This work describes the construction of covalent-organic frameworks (COFs) modified with glyco-moieties to serve as hepato-targeted multitherapy delivery systems. They combine minimally invasive interventional photodynamic therapy (IPDT) triggered synergism with chemotherapy treatment for hepatocellular carcinoma (HCC). With the aid of minimally invasive intervention, PDT can elicit potent anti-cancer activity for deep solid tumors. This platform shows strong therapeutic outcomes in both subcutaneous and orthotopic mouse models, which can significantly prolong survival. This work showed an effective combination of a biomedical nano-formulation with the clinical operational means in cancer treatment, which is greatly promising in clinical translation.
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http://dx.doi.org/10.1016/j.actbio.2022.06.012DOI Listing
June 2022

Sunken oil detection and classification using MBES backscatter data.

Mar Pollut Bull 2022 Jul 9;180:113795. Epub 2022 Jun 9.

School of Hydraulic Engineering, Ludong University, Yantai, China. Electronic address:

Sunken oil incidents have occurred multiple times in the Bohai Sea over the past ten years. Currently, quick and effective sunken oil detection and classification remains a difficult problem. In this study, sonar detection experiments are conducted to obtain acoustic image samples using a multibeam echosounder (MBES) in a large seawater tank at the bottom of the area where the sunken oil is located. A series of MBES data corrections are constructed to generate backscatter strength images that can reflect the target characteristics directly. Meanwhile, eight-dimensional features are extracted, and a support vector machine (SVM) classification framework is built to classify the sunken oil and other interference targets. The results indicate that the MBES backscatter images provide an alternative approach for detecting and classifying sunken oil. The overall target classification accuracy reaches 88.5% by the SVM algorithm. Thus, this study provides a basis for further investigation of detecting sunken oil.
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http://dx.doi.org/10.1016/j.marpolbul.2022.113795DOI Listing
July 2022

Covalent Triazine Frameworks and Porous Carbons: Perspective from an Azulene-Based Case.

Macromol Rapid Commun 2022 Jun 9:e2200392. Epub 2022 Jun 9.

The Meso-Entropy Matter Lab, State Key Laboratory of Metal Matrix Composites, Shanghai Key Laboratory of Electrical Insulation and Thermal Ageing, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China.

Covalent triazine frameworks (CTFs) are among the most valuable frameworks owing to many fantastic properties. However, molten salt-involved preparation of CTFs at 400-600 °C causes debate on whether CTFs represent organic frameworks or carbon. Herein, new CTFs based on the 1,3-dicyanoazulene monomer (CTF-Azs) are synthesized using molten ZnCl at 400-600 °C. Chemical structure analysis reveals that the CTF-Az prepared at low temperature (400 °C) exhibits polymeric features, whereas those prepared at high temperatures (600 °C) exhibit typical carbon features. Even after being treated at even higher temperatures, the CTF-Azs retain their rich porosity, but the polymeric features vanish. Although structural de-conformation is a widely accepted outcome in polymer-to-carbon rearrangement processes, the study evaluates such processes in the context of CTF systems. A proof-of-concept study is performed, observing that the as-synthesized CTF-Azs exhibit promising performance as cathodes for Li- and K-ion batteries. Moreover, the as-prepared NPCs exhibit excellent catalytic oxygen reduction reaction (ORR) performance; hence, they can be used as air cathodes in Zn-air batteries. This study not only provides new building blocks for novel CTFs with controllable polymer/carbon features but also offers insights into the formation and structure transformation history of CTFs during thermal treatment.
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http://dx.doi.org/10.1002/marc.202200392DOI Listing
June 2022

Gram-selective antibacterial peptide hydrogels.

Biomater Sci 2022 Jun 9. Epub 2022 Jun 9.

Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China.

The human microbiome plays fundamental roles in human health and disease. However, widely used broad-spectrum antibiotics severely disrupt human-related microbial communities, eventually leading to resistant bacteria, posing a growing threat to global medical health. Antimicrobial peptides (AMPs) are promising antimicrobial agents that barely cause bacterial resistance. Excellent broad-spectrum antimicrobial activities have been achieved using hydrogels self-assembled from AMPs, but there is still a lack of AMP hydrogels that can target Gram-positive and Gram-negative bacteria. Herein, several hydrogels self-assembled from AMPs, termed IK1, IK3, and IK4, were designed and synthesized. antibacterial results indicated that the IK1 and IK4 hydrogels specifically targeted Gram-positive and Gram-negative bacteria, respectively, while the IK3 hydrogel targeted both Gram-positive and Gram-negative bacteria. The desired broad-spectrum or Gram-selective AMP hydrogels are believed to be obtained through the rational design of the hydrophilicity, hydrophobicity, and charge properties of the peptide molecules. Good Gram-selective antibacterial properties and the ability to promote wound healing have been demonstrated treating mouse wound models with these AMP hydrogels. We believe that these Gram-selective AMP hydrogels could potentially have important applications in treating common recurring infections.
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http://dx.doi.org/10.1039/d2bm00558aDOI Listing
June 2022

Subset selection strategy-based pancreas segmentation in CT.

Quant Imaging Med Surg 2022 Jun;12(6):3061-3077

Center for Intelligent Oncology, Chongqing University Cancer Hospital, Chongqing, China.

Background: Although convolutional neural network (CNN)-based methods have been widely used in medical image analysis and have achieved great success in many medical segmentation tasks, these methods suffer from various imbalance problems, which reduce the accuracy and validity of segmentation results.

Methods: We proposed two simple but effective sample balancing methods, positive-negative subset selection (PNSS) and hard-easy subset selection (HESS) for foreground-to-background imbalance and hard-to-easy imbalance problems in medical segmentation tasks. The PNSS method gradually reduces negative-easy slices to enhance the contribution of positive pixels, and the HESS method enhances the iteration of hard slices to assist the model in paying greater attention to the feature extraction of hard samples.

Results: The proposed methods greatly improved the segmentation accuracy of the worst case (samples with the worst segmentation results) on the public National Institutes of Health (NIH) clinical center pancreatic segmentation dataset, and the minimum dice similarity coefficient (DSC) was improved by nearly 5%. Furthermore, performance gains were also observed with the proposed methods in liver segmentation (the minimum DSC increased from 75.03% to 84.29%), liver tumor segmentation (the minimum DSC increased from 20.92% to 35.73%), and brain tumor segmentation (the minimum DSC increased from 21.97% to 30.38%) on different neural networks. These results indicate that the proposed methods are effective and robust.

Conclusions: Our proposed method can effectively alleviate foreground-to-background imbalance and hard-to-easy imbalance problems, and can improve segmentation accuracy, especially for the worst case, which guarantees the reliability of the proposed methods in clinical applications.
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http://dx.doi.org/10.21037/qims-21-798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9131347PMC
June 2022

Exploring the ozone pollution over the western Sichuan Basin, Southwest China: The impact of diurnal change in mountain-plains solenoid.

Sci Total Environ 2022 Sep 27;839:156264. Epub 2022 May 27.

State Key Laboratory of Severe Weather, Chinese Academy of Meteorological Sciences, China Meteorological Administration, Beijing 100081, China.

The Sichuan Basin (SCB), to the east of the Tibetan Plateau (TP), experiences severe ozone (O) pollution. Unfavorable atmospheric diffusion conditions are considered the main causes of heavy air pollution over the basin. However, the meteorological impact of thermally driven mountain-plains solenoid (MPS) between the TP and SCB on O pollution has not been reported. Here we show the MPS driving the diurnal O changes in the atmospheric boundary layer over the SCB based on surface and high-resolution vertical observations, ERA5 reanalysis data, and the WRF-Chem model. The MPS shifts between upslope and easterly flows along the eastern slope of the TP and SCB during the day and downslope westerly flows to the western SCB at night. The daytime MPS flows drive the westward transport of O-rich air mass in the atmospheric boundary layer from the polluted SCB and accumulate high O levels from the western edge of the SCB to the eastern slope of TP, subsequently aggravating O pollution in this region. After sunset, the MPS drainage flows carry air containing elevated O eastward downslope along the eastern slope of the TP into the nocturnal residual layer, enhancing the O concentrations aloft over the western SCB. The high-level O in the residual layer is transported downstream by nocturnal prevailing winds and contributes significantly to the next-day surface O buildup in the downwind region through daytime vertical mixing (~30 μg m h). The present study reveals a transport mechanism driven by the MPS with coupling diurnal changes in the atmospheric boundary layer, which redistributes O over the basin and exacerbates O pollution along the western edge of the basin. This study has important implications for understanding meteorological drivers on atmospheric environment underlying the complex terrain.
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http://dx.doi.org/10.1016/j.scitotenv.2022.156264DOI Listing
September 2022

Towards biomass production and wastewater treatment by enhancing the microalgae-based nutrients recovery from liquid digestate in an innovative photobioreactor integrated with dialysis bag.

J Environ Manage 2022 Sep 25;317:115337. Epub 2022 May 25.

School of Life Sciences, Nanjing Normal University, Nanjing, 210023, China.

Microalgae-based nutrients recovery from liquid anaerobic digestate of swine manure has been a hotspot in recent decades. Nevertheless, in consideration of the high NH-N content and poor light penetrability exhibited by the original liquid digestate, uneconomical pretreatment on liquid digestate including centrifugation and dilution are indispensable before microalgae cells inoculation. Herein, aiming at eliminating the energy-intensive and freshwater-consuming pretreatment on liquid digestate and enhancing microalgae growth, the dialysis bag which permits nutrients transferring across its wall surface whereas retains almost all matters characterized by impeding light transmission within the raw liquid digestate was integrated into a column photobioreactor (DB-PBR). Consequently, light availability of microalgae cells in DB-PBR was elevated remarkably and thus contributed to a 357.58% improvement on microalgae biomass concentration in DB-PBR than the conventional PBR under 80 μmol m s. Likewise, superior nutrients removal efficiencies from liquid digestate were obtained in DB-PBR (NH-N: 74.84%, TP: 63.75%) over the conventional PBR (NH-N: 30.27%, TP: 16.86%). Furthermore, higher microalgae biomass concentration (1.87 g L) and nutrients removal efficiencies (NH-N: 95.12%, TP: 76.87%) were achieved in the DB-PBR by increasing the light intensity to 140 μmol m s. More importantly, the DB-PBR may provide a simple and greener solution to purify other kinds of wastewater.
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http://dx.doi.org/10.1016/j.jenvman.2022.115337DOI Listing
September 2022

Exploring the translation process for multilingual implementation research studies: a collaborative autoethnography.

BMJ Glob Health 2022 05;7(5)

Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada

Introduction: In an increasingly globalised and interconnected world, evidence to evaluate complex interventions may be generated in multiple languages. However, despite its influence in shaping the evidence base, there is little literature explicitly connecting the translation process to the goals and processes of implementation research. This study aims to explore the processes and experience of an international implementation research team conducting a process evaluation of a complex intervention in Tibet Autonomous Region, China.

Methods: This study uses a collaborative autoethnographic approach to explore the translation process from Chinese or Tibetan to English of key stakeholder interview transcripts. In this approach, multiple researchers and translators contributed their reflections, and conducted joint analysis through dialogue, reflection and with consideration of multiple perspectives. Seven researchers involved with the translation process contributed their perspectives through in-depth interviews or written reflections and jointly analysed the resulting data.

Results: We describe the translation process, synthesise key challenges including developing a 'voice' and tone as a translator, conveying the depth of idioms across languages, and distance from the study context. We further offer lessons learnt including the importance of word banks with unified translations of words and phrases created iteratively during the translation process, the need to collaborate between translators and the introspective work necessary for translators to explore their positionality and reflexivity during the work. We then offer a summary of these learnings for other implementation research teams.

Conclusion: Our findings emphasise that in order to ensure rigour in their work, implementation research teams using qualitative data should make concerted effort to consider both the translation process as well as its outcomes. Given the numerous multinational or multilingual implementation research studies using qualitative methods, there is a need for further consideration and reflection on the translation process.
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http://dx.doi.org/10.1136/bmjgh-2022-008674DOI Listing
May 2022

Fudosteine attenuates acute lung injury in septic mice by inhibiting pyroptosis via the TXNIP/NLRP3/GSDMD pathway.

Eur J Pharmacol 2022 Jul 21;926:175047. Epub 2022 May 21.

Division of Pulmonary Diseases, State Key Laboratory of Biotherapy, and Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, China. Electronic address:

There is a dearth of effective pharmacotherapies for sepsis-induced acute lung injury/acute respiratory distress syndrome (ALI/ARDS) to which oxidative stress and excessive inflammation are major contributors. We hypothesized that fudosteine, a cysteine derivative, may protect against sepsis-induced ALI/ARDS given its anti-oxidant capacity. This study aimed to investigate the effects and mechanisms of fudosteine in a mouse model of sepsis-induced ALI. Sepsis was induced by cecal ligation and puncture (CLP). The intragastrical administration of fudosteine (25 mg/kg, 50 mg/kg, and 100 mg/kg) dose-dependently decreased proinflammatory cytokine levels in bronchoalveolar lavage fluid (BALF) and serum and reduced BALF/serum albumin and lung wet/dry weight ratios in septic mice. The lung injury score was significantly lowered by fudosteine [e.g., 0.18 ± 0.03 (100 mg/kg) vs. 0.42 ± 0.03 (CLP), P < 0.0001]. Fudosteine also reduced the biomarkers of lung epithelial injury in BALF and markedly improved oxidative stress indicators in lung tissues [e.g., malondialdehyde: 337.70 ± 23.78 (100 mg/kg) vs. 686.40 ± 28.36 (CLP) nmol/mg protein, P < 0.0001]. Lung tissue transcriptomics analyses revealed suppressed inflammatory responses and oxidative stress with fudosteine and the involvement of the inflammasome and pyroptosis pathways. Western blot analyses indicated that fudosteine inhibited the sepsis-induced activation of gasdermin D (GSDMD) and caspase-1 and the upregulation of thioredoxin-interacting protein (TXNIP), nucleotide-binding domain, leucine-rich repeat-containing receptor, pyrin domain-containing-3 (NLRP3), and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC). Fudosteine therefore protects against sepsis-induced ALI in mice, and the inhibition of pyroptosis via the TXNIP/NLRP3/GSDMD pathway may be an underlying mechanism.
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http://dx.doi.org/10.1016/j.ejphar.2022.175047DOI Listing
July 2022

NEDD4L inhibits cell viability, cell cycle progression, and glutamine metabolism in esophageal squamous cell carcinoma via ubiquitination of c-Myc.

Acta Biochim Biophys Sin (Shanghai) 2022 May 25. Epub 2022 May 25.

Department of Hematologic and Oncology, Xinjiang Clinical Research Center for Precision Medicine of Digestive System Tumor, the Center Hospital of Karamay City, Karamay 834000, China.

Esophageal squamous cell carcinoma (ESCC) is a common subtype of esophageal cancer with high incidence. Surgery remains the main strategy for treatment of ESCC at early stage. However, the treatment outcome is unsatisfactory. Therefore, finding new therapeutics is of great importance. In the present study, we measured the level of NEDD4L, an ubiquitin protein ligase, in clinical samples and investigated the effects of NEDD4L on cell viability, cell cycle progression, and glutamine metabolism in TE14 cells determined by CCK-8 assay, flow cytometry and biochemical analysis, respectively. The results show that NEDD4L is significantly decreased in ESCC specimens, and its decreased expression is associated with a poor clinical outcome. Overexpression of NEDD4L significantly inhibits cell viability, cell cycle progression, and glutamine metabolism in TE14 cells. Mechanistic study indicates that NEDD4L regulates tumor progression through ubiquitination of c-Myc and modulation of glutamine metabolism. NEDD4L inhibits cell viability, cell cycle progression, and glutamine metabolism in ESCC by ubiquitination of to decrease the expressions of GLS1 and SLC1A5. Our findings highlight the importance of NEDD4L/c-Myc signaling in ESCC.
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http://dx.doi.org/10.3724/abbs.2022048DOI Listing
May 2022

Selective CO Photoreduction to CH via Pd -Assisted Hydrodeoxygenation over CeO Nanosheets.

Angew Chem Int Ed Engl 2022 May 19:e202203249. Epub 2022 May 19.

Hefei National Research Center for Physical Science at Microscale, National Synchrotron Radiation Laboratory, University of Science and Technology of China, Hefei, 230026, P. R. China.

Here, noble-metal-doped two-dimensional metal oxide nanosheets are designed to realize selective CO photoreduction to CH . As a prototype, Pd-doped CeO nanosheets are fabricated, where the active sites of Pd (2<δ<4) and Ce -O are revealed by quasi in situ X-ray photoelectron spectra and in situ electron paramagnetic resonance spectra. Moreover, in situ Fourier-transform infrared spectra of D O photodissociation and desorption verify the existence of the Pd-OD bond, implying that Pd sites can participate in water oxidation to deliver H* species for facilitating the protonation of the intermediates. Furthermore, theoretical calculations suggest the Pd doping could regulate the formation energy barrier of the key intermediates CO* and CH O*, thus making CO reduction to CH become the favorable process. Accordingly, Pd-doped CeO nanosheets achieve nearly 100 % CH selectivity of CO photoreduction, with the raising CH evolution rate of 41.6 μmol g  h .
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http://dx.doi.org/10.1002/anie.202203249DOI Listing
May 2022

Ferroptosis and Apoptosis Are Involved in the Formation of L-Selenomethionine-Induced Ocular Defects in Zebrafish Embryos.

Int J Mol Sci 2022 Apr 26;23(9). Epub 2022 Apr 26.

School of Life Science, Nanchang University, Nanchang 330031, China.

Selenium is an essential trace element for humans and other vertebrates, playing an important role in antioxidant defense, neurobiology and reproduction. However, the toxicity of excessive selenium has not been thoroughly evaluated, especially for the visual system of vertebrates. In this study, fertilized zebrafish embryos were treated with 0.5 µM L-selenomethionine to investigate how excessive selenium alters zebrafish eye development. Selenium-stressed zebrafish embryos showed microphthalmia and altered expression of genes required for retinal neurogenesis. Moreover, ectopic proliferation, disrupted mitochondrial morphology, elevated ROS-induced oxidative stress, apoptosis and ferroptosis were observed in selenium-stressed embryos. Two antioxidants-reduced glutathione (GSH) and N-acetylcysteine (NAC)-and the ferroptosis inhibitor ferrostatin (Fer-1) were unable to rescue selenium-induced eye defects, but the ferroptosis and apoptosis activator cisplatin (CDDP) was able to improve microphthalmia and the expression of retina-specific genes in selenium-stressed embryos. In summary, our results reveal that ferroptosis and apoptosis might play a key role in selenium-induced defects of embryonic eye development. The findings not only provide new insights into selenium-induced cellular damage and death, but also important implications for studying the association between excessive selenium and ocular diseases in the future.
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http://dx.doi.org/10.3390/ijms23094783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9100823PMC
April 2022

miR-146a Maintains Immune Tolerance of Kupffer Cells and Facilitates Hepatitis B Virus Persistence in Mice.

J Immunol 2022 Jun 13;208(11):2558-2572. Epub 2022 May 13.

Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China;

Kupffer cells (KCs), the largest tissue-resident macrophage population in the body, play a central role in maintaining a delicate balance between immune tolerance and immunity in the liver. However, the underlying molecular mechanism remains elusive. In this study, we show that KCs express high levels of miR-146a, which is under control of the PU.1 transcription factor. miR-146a deficiency promoted KCs differentiation toward a proinflammatory phenotype; conversely, miR-146a overexpression suppressed this phenotypic differentiation. We found that hepatitis B virus (HBV) persistence or HBV surface Ag treatment significantly upregulated miR-146a expression and thereby impaired polarization of KCs toward a proinflammatory phenotype. Furthermore, in an HBV carrier mouse model, KCs depletion by clodronate liposomes dramatically promoted HBV clearance and enhanced an HBV-specific hepatic CD8 T cell and CD4 T cell response. Consistent with this finding, miR-146a knockout mice cleared HBV faster and elicited a stronger adaptive antiviral immunity than wild-type mice. In vivo IL-12 blockade promoted HBV persistence and tempered the HBV-specific CTL response in the liver of miR-146a knockout mice. Taken together, our results identified miR-146a as a critical intrinsic regulator of an immunosuppressive phenotype in KCs under inflammatory stimuli, which may be beneficial in maintenance of liver homeostasis under physiological condition. Meanwhile, during HBV infection, miR-146a contributed to viral persistence by inhibiting KCs proinflammatory polarization, highlighting its potential as a therapeutic target in HBV infection.
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http://dx.doi.org/10.4049/jimmunol.2100618DOI Listing
June 2022

Metformin Inhibits Multiple Myeloma Serum-induced Endothelial Cell Thrombosis by Down-Regulating miR-532.

Ann Vasc Surg 2022 May 10. Epub 2022 May 10.

Department of Neurology, Karamay Central Hospital, Karamay, China. Electronic address:

Background: Thrombotic complications in multiple myeloma (MM) impairs the quality of life in patients. Metformin has a certain effect on anti-thrombosis, but its role and mechanism in MM-induced thrombosis are still uncovered. Therefore, this study evaluated the effect of metformin on MM-induced thrombosis.

Methods: Human umbilical vein endothelial cells (HUVECs) were exposed to normal serum (15%), MM serum (15%), metformin (0.01 mmol/L), or MM serum, and metformin simultaneously. The expression of tissue factor (TF) in HUVECs was detected by flow cytometry and quantitative real-time polymerase chain reaction PCR (qRT-PCR). QRT-PCR was also used to determine the expressions of endothelial protein C receptor (EPCR) and miR-532. The generation of thrombin and activated protein C was measured by thrombin generation and protein C activation assays. EPCR, extracellular signal-regulated kinase (ERK) 1/2, p38 mitogen activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) pathway related protein expressions were detected by western blot.

Results: MM serum increased the expressions of TF and miR-532, induced thrombin generation, inhibited EPCR and protein C activation in HUVECs. And metformin could reverse the effects of MM serum on the expressions of TF, EPCR and miR-532, thrombin generation, protein C activation in HUVECs. However, miR-532 mimic reversed the effects of metformin and promoted the levels of thrombosis-related indicators in HUVECs. Moreover, metformin activated the ERK 1/2, p38 MAPK, and NF-κB pathways but miR-532 mimic suppressed the pathway activation.

Conclusions: Metformin played an inhibitory effect on MM serum-induced HUVEC thrombosis, suggesting that metformin could serve as a novel antithrombotic approach for MM patients.
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http://dx.doi.org/10.1016/j.avsg.2022.04.035DOI Listing
May 2022

Overcoming resistance to oncolytic virus M1 by targeting PI3K-γ in tumor-associated myeloid cells.

Mol Ther 2022 May 11. Epub 2022 May 11.

Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China. Electronic address:

Oncolytic viruses (OVs) have become a category of promising anticancer immunotherapeutic agents over the last decade. However, the fact that many individuals fail to respond to OVs highlights the importance of defining the barely known immunosuppressive mechanisms that lead to treatment resistance. Here we found that the immunosuppression mediated by tumor-associated myeloid cells (TAMCs) directly quenches the antitumor effect of oncolytic virus M1 (OVM). OVM induces myeloid cells to migrate into tumors and strengthens their immunosuppressive phenotypes. Mechanically, tumor cells treated with OVM secrete interleukin-6 (IL-6) to activate the phosphatidylinositol 3-kinase (PI3K)-γ/Akt axis in TAMCs, promoting infiltration of TAMCs and aggravating their inhibition on cytotoxic CD8 T lymphocytes. Pharmacologically targeting PI3K-γ relieves TAMC-mediated immunosuppression and enhances the efficacy of OVM. Additional treatment with immune checkpoint antibodies eradicates multiple refractory solid tumors and induces potent long-term antitumor immune memory. Our findings indicate that OVM functions as a double-edged sword in antitumor immunity and provide insights into the rationale for liberating T cell-mediated antitumor activity by abolishing TAMC-mediated immunosuppression.
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http://dx.doi.org/10.1016/j.ymthe.2022.05.008DOI Listing
May 2022

Excessive selenium affects neural development and locomotor behavior of zebrafish embryos.

Ecotoxicol Environ Saf 2022 Jun 5;238:113611. Epub 2022 May 5.

School of Life Science, Key Laboratory of Aquatic Resources and Utilization of Jiangxi, Nanchang University, Nanchang 330031, China. Electronic address:

Selenium is an essential micronutrient derived from daily diet to maintain the normal growth and development of vertebrates. Excessive selenium intake will induce cardiovascular toxicity, reproductive toxicity and neurotoxicity. However, there have been few studies of the toxic effects of selenium on neural development and locomotor behavior. In this study, newly fertilized zebrafish embryos were treated with selenium. As a result, selenium treatment at the concentration of 0.5 µM decreased the moving speed and distance and blunted the touch response of zebrafish embryos. TUNEL assay and immunofluorescence analysis revealed that selenium induced nervous system impairment including promoted cell apoptosis, proliferation and neuroinflammation, and decreased neurons in zebrafish embryos. RNA-seq and RT-PCR results indicated that selenium treatment significantly decreased the expression of the dopaminergic neuron, motor neuron, GABAergic neuron and neurotransmitter transport marker genes in zebrafish embryos. The expression of PPAR signaling pathway marker genes was significantly down-regulated in selenium-treated embryos. Two PPAR agonists (rosiglitazone and bezafibrate) and an anti-cancer drug (cisplatin) were tested for their effects to alleviate selenium-induced locomotor defects. Rosiglitazone and bezafibrate could restore the expression of some neural marker genes but could not fully rescue the selenium-induced locomotor behavior defects. The supplementation of cisplatin could restore the dysfunctional locomotor behavior and the abnormal expression of the PPAR and neural marker genes to almost the normal levels. In conclusion, the results of this study reveal that selenium-induced neural development and locomotor behavior defects are caused by multiple complex factors including PPAR signaling, and all the factors might be recovered by cisplatin through unknown mechanisms.
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http://dx.doi.org/10.1016/j.ecoenv.2022.113611DOI Listing
June 2022

Screening of lncRNA-miRNA-mRNA Coexpression Regulatory Networks Involved in Acute Traumatic Coagulation Dysfunction Based on CTD, GeneCards, and PharmGKB Databases.

Oxid Med Cell Longev 2022 19;2022:7280312. Epub 2022 Apr 19.

Department of General Surgery, Xiangya Hospital, Central South University, Changsha 410008 P. R., China.

Competitive endogenous RNA (ceRNA) networks play crucial roles in multiple biological processes and development of diseases. They might serve as diagnostic and prognosis markers as well as therapeutic targets. The purpose of this study was to identify a novel ceRNA network involving KCNQ1OT1, hsa-miR-24-3p, and VWF in acute traumatic coagulopathy (ATC) based on databases search. We searched the CTD, GeneCards, and PharmGKB databases for ATC-related target genes using Coagulopathy as a keyword. Upstream miRNAs and lncRNAs of the candidate target VWF were then explored using the miRWalk, microT, TargetScan, RNA22 and Tarbase, and DIANA-LncBase and Starbase databases, respectively. A KCNQ1OT1-hsa-miR-24-3p-VWF ceRNA network was constructed by "ggalluvial" package. Interaction between KCNQ1OT1, hsa-miR-24-3p, and VWF was examined, and their expression was quantified in the peripheral blood samples from 30 ATC patients and liver tissues of ATC rat models. Forty-one ATC-related target genes were identified following data retrieval from publicly available databases, of which VWF was selected as the target and used for the subsequent analysis. KCNQ1OT1 and hsa-miR-24-3p were confirmed to be the key upstream regulatory factors of VWF. KCNQ1OT1-hsa-miR-24-3p-VWF coexpression regulatory network was constructed where KCNQ1OT1 competitively bound to hsa-miR-24-3p and attenuated its binding to VWF. Both the liver tissues of ATC rats and peripheral blood samples from ATC patients showed increased hsa-miR-24-3p expression and decreased VWF and KCNQ1OT1 expression. Collectively, we described the KCNQ1OT1-hsa-miR-24-3p-VWF ceRNA network in the development of ATC. We propose a new ceRNA that could help in the diagnosis and treatment of ATC.
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http://dx.doi.org/10.1155/2022/7280312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9042625PMC
May 2022

Radiomics Nomogram for Predicting Stroke Recurrence in Symptomatic Intracranial Atherosclerotic Stenosis.

Front Neurosci 2022 12;16:851353. Epub 2022 Apr 12.

Department of Magnetic Resonance Imaging (MRI), Shaanxi Provincial People's Hospital, Xi'an, China.

Objective: To develop and validate a radiomics nomogram for predicting stroke recurrence in symptomatic intracranial atherosclerotic stenosis (SICAS).

Methods: The data of 156 patients with SICAS were obtained from the hospital database. Those with and without stroke recurrence were identified. The 156 patients were separated into a training cohort ( = 110) and a validation cohort ( = 46). Baseline clinical data were collected from our medical records, and plaque radiological features were extracted from vascular wall high-resolution imaging (VW-HRMRI). The imaging sequences included 3D-T1WI-VISTA, T2WI, and 3D-T1WI-VISTA-enhanced imaging. Least absolute shrinkage and selection operator (LASSO) analysis were used to select the radiomics features associated with stroke recurrence. Then, multiple logistic regression analysis of clinical risk factors, radiological features, and radiomics signatures were performed, and a predictive nomogram was constructed to predict the probability of stroke recurrence in SICAS. The performance of the nomogram was evaluated.

Results: Diabetes mellitus, plaque burden, and enhancement ratio were independent risk factors for stroke recurrence [odds ratio (OR) = 1.24, 95% confidence interval (CI): 1.04-3.79, = 0.018; OR = 1.76, per 10% increase, 95% CI, 1.28-2.41, < 0.001; and OR = 1.94, 95% CI: 1.27-3.09, < 0.001]. Five features of 3D-T1WI-VISTA, six features of T2WI, and nine features of 3D-T1WI-VISTA-enhanced images were associated with stroke recurrence. The radiomics signature in 3D-T1WI-VISTA-enhanced images was superior to the radiomics signature of the other two sequences for predicting stroke recurrence in both the training cohort [area under the curve (AUC), 0.790, 95% CI: 0.669-0.894] and the validation cohort (AUC, 0.779, 95% CI: 0.620-0.853). The combination of clinical risk factors, radiological features, and radiomics signature had the best predictive value (AUC, 0.899, 95% CI: 0.844-0.936 in the training cohort; AUC, 0.803, 95% CI: 0.761-0.897 in the validation cohort). The C-index of the nomogram was 0.880 (95% CI: 0.805-0.934) and 0.817 (95% CI: 0.795-0.948), respectively, in the training and validation cohorts. The decision curve analysis further confirmed that the radiomics nomogram had good clinical applicability with a net benefit of 0.458.

Conclusion: The radiomics features were helpful to predict stroke recurrence in patients with SICAS. The nomogram constructed by combining clinical high-risk factors, plaque radiological features, and radiomics features is a reliable tool for the individualized risk assessment of predicting the recurrence of SICAS stroke.
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http://dx.doi.org/10.3389/fnins.2022.851353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9039339PMC
April 2022
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