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TOXICOLOGY MECHANISMS AND METHODS · 2026 · IF 2.9

Unveiling the neurodevelopmental toxicity of PFOA and PFOS: evidence from integration of in silico and in vitro study

Lili Xin,Rui Guo,Jiawei Sun,Yue Su,Jiahang Cai,Wanzhen Li,Zhongxiao Wan,Jianshu Wang

Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are well-known neurodevelopmental toxicants, but the potential molecular mechanism needs to be further clarified. This study aimed to investigate the underlying mechanism of PFOA and PFOS-induced neurodevelopmental toxicity by integrating network toxicology, transcriptomic data from autism spectrum disorder patients and in vitro study. Network toxicology identified 42 core targets that enriched in a total of 105 significant GO entries and 142 KEGG pathways. With the disease-context comparison from the transcriptomic, 10 hub targets and 22 common KEGG pathways were identified. Cellular senescence-associated responses including cellular senescence and cell cycle were proposed as one of the potential mechanisms underlying PFOA and PFOS co-exposure-induced neurodevelopmental toxicity. Molecular docking analysis showed that PFOA and PFOS elicits potential binding capacities with hub targets, with TP53 and MAPK 13 exhibiting lower binding energies with both PFASs, further predicting the potential role of these targets in PFASs-induced neurodevelopmental toxicity. After PFOA and PFOS co-treatment, reduced cell viability, a senescence-like phenotype characterized by cell cycle arrest and increased positive senescence β-galactosidase, upregulation of senescence-associated biomarkers including TP53, p53, p21 and IL-6 as well as the significant up-regulation of MAPK1, MAPK3, MAPK13 and MAPK14 genes were observed in human neuroblastoma SH-SY5Y cells. Thereafter, these findings suggested the multi-target and multi-pathway characteristic of PFOA and PFOS co-exposure-induced neurodevelopmental toxicity with cellular senescence-associated responses as one of the potential molecular mechanisms.

CAS / MDL: 1763-23-1
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BIOLOGICAL RESEARCH · 2023 ·Vol. 56 ·期 1 ·1-14 · IF 6.7

Role of SYVN1 in the control of airway remodeling in asthma protection by promoting SIRT2 ubiquitination and degradation

Dai Bing,Liu Si,Shen Wenxin,Chen Li,Zhou Qianlan,Han Lina,Zhang Qinzhen,Shan Lishen

Background Asthma is a heterogenous disease that characterized by airway remodeling. SYVN1 (Synoviolin 1) acts as an E3 ligase to mediate the suppression of endoplasmic reticulum (ER) stress through ubiquitination and degradation. However, the role of SYVN1 in the pathogenesis of asthma is unclear. Results In the present study, an ovalbumin (OVA)-induced murine model was used to evaluate the effect of SYVN1 on asthma. An increase in SYVN1 expression was observed in the lungs of mice after OVA induction. Overexpression of SYVN1 attenuated airway inflammation, goblet cell hyperplasia and collagen deposition induced by OVA. The increased ER stress-related proteins and altered epithelial-mesenchymal transition (EMT) markers were also inhibited by SYVN1 in vivo. Next, TGF-β1-induced bronchial epithelial cells (BEAS-2B) were used to induce EMT process in vitro. Results showed that TGF-β1 stimulation downregulated the expression of SYVN1, and SYVN1 overexpression prevented ER stress response and EMT process in TGF-β1-induced cells. In addition, we identified that SYVN1 bound to SIRT2 and promoted its ubiquitination and degradation. SIRT2 overexpression abrogated the protection of SYVN1 on ER stress and EMT in vitro. Conclusions These data suggest that SYVN1 suppresses ER stress through the ubiquitination and degradation of SIRT2 to block EMT process, thereby protecting against airway remodeling in asthma.

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INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · 2023 ·Vol. 64 ·期 14 ·30-30 · IF 4.4

O-GlcNAcylation Inhibition Upregulates Connexin43 Expression in the Endothelium to Protect the Tight Junction Barrier in Diabetic Retinopathy

Guodong Liu,Le Feng,Xiaoqiang Liu,Peng Gao,Fang Wang

Purpose:This study aimed to investigate the effects of O-linked N-acetylglucosamine modification (O-GlcNAcylation) on connexin43 (Cx43) expression and its subsequent effects on tight junction properties in diabetic retinopathy (DR).Methods:O-GlcNAcylation levels in primary human retinal vascular endothelial cells (HRVECs) and retinas from rats with diabetes were regulated by treatment with Thiamet G or alloxan. Immunoprecipitation was used to examine the relationship between O-GlcNAcylation and Cx43 expression. Stable overexpression and knockdown of Cx43 in HRVECs were achieved using lentivirus constructs; further, their effects on occludin and zonula occluden-1 (ZO-1) expression and tight junction barrier function were determined.Results:O-GlcNAcylation level increased significantly, whereas Cx43 expression decreased in retinas from rats with diabetes and HRVECs cultured under high-glucose conditions. Immunoprecipitation revealed that Cx43 was modified by O-GlcNAcylation and phosphorylation simultaneously. O-GlcNAcylation inhibition negatively regulated both total Cx43 and phosphorylated Cx43 expression, subsequently disrupting tight junction properties. Conversely, Cx43 overexpression reversed the disruption of tight junction properties and downregulated vascular endothelial growth factor expression. Consistently, Cx43 overexpression increased transendothelial electrical resistance values in HRVEC layers.Conclusions:O-GlcNAcylation negatively regulated Cx43 expression, contributing to the disruption of the blood retinal barrier. However, O-GlcNAcylation inhibition and Cx43 overexpression could reverse the tight junction disruption. Therefore, O-GlcNAcylation inhibition is a potential target for avoiding tight junction disruption through the Cx43 pathway in DR.

CAS / MDL: 314-13-6
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MOLECULES · 2023 ·Vol. 28 ·期 22 ·7515 · IF 4.6

Copper Nanoparticles Confined in a Silica Nanochannel Film for the Electrochemical Detection of Nitrate Ions in Water Samples

Dewang Li,Shuai Xu,Haiyan Jin,Jinqing Wang,Fei Yan

The nitrate ion (NO3−) is a typical pollutant in environmental samples, posing a threat to the aquatic ecosystem and human health. Therefore, rapid and accurate detection of NO3−is crucial for both the aquatic sciences and government regulations. Here we report the fabrication of an amino-functionalized, vertically ordered mesoporous silica film (NH2-VMSF) confining localized copper nanoparticles (CuNPs) for the electrochemical detection of NO3−. NH2-VMSF-carrying amino groups possess an ordered perpendicular nanochannel structure and ultrasmall nanopores, enabling the confined growth of CuNPs through the electrodeposition method. The resulting CuNPs/NH2-VMSF-modified indium tin oxide (ITO) electrode (CuNPs/NH2-VMSF/ITO) combines the electrocatalytic reduction ability of CuNPs and the electrostatic attraction capacity of NH2-VMSF towards NO3−. Thus, it is a rapid and sensitive electrochemical method for the determination of NO3−with a wide linear detection range of 5.0–1000 μM and a low detection limit of 2.3 μM. Direct electrochemical detection of NO3−in water samples (tap water, lake water, seawater, and rainwater) with acceptable recoveries ranging from 97.8% to 109% was performed, demonstrating that the proposed CuNPs/NH2-VMSF/ITO sensor has excellent reproducibility, regeneration, and anti-interference abilities.Keywords:copper nanoparticles;silica nanochannel film;nitrate ions;electrochemical sensor;water samples

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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2023 · IF 8.2

Chemical profile of Roselle extract and its inhibitory activities on three digestive enzymes in vitro and in vivo

Dan Yang,Xin-yu-yao Ding,Hai-Xia Xu,Yu-Xian Guo,Qing-Feng Zhang

Roselle is rich in an extensive diversity of beneficial substances, including phenolic acids, amino acids, anthocyanins, vitamins, and flavonoids. Herein, the chemical constituents in Roselle extract (RE) were identified by UPLC-DAD-QTOF-MS. Besides, its inhibitory effects on three digestive enzymes, i.e. α-amylase, α-glucosidase, and pancreatic lipase, were investigated in both in vitro and in vivo . Thirty-three constituents including hibiscus acid, 18 phenolic acids, 2 anthocyanins and 12 flavonoids were identified. The anthocyanins content in RE was 21.44 ± 0.68 %, while the contents of chlorogenic acids, rutin and quercetin were 17.76 ± 2.28 %, 0.31 ± 0.01 % and 0.32 ± 0.01 %, respectively. RE inhibited pancreatic lipase in a non-competitive way with an IC 50 value of 0.84 mg/mL. Besides, it demonstrated a mixed-type inhibition on both α-glucosidase and α-amylase with IC 50 values of 0.59 mg/mL and 1.93 mg/mL, respectively. Fluorescence quenching assays confirmed the binding of RE to the enzyme proteins. Furthermore, rats pre-treated with RE at doses of 50 and 100 mg/kg body weight (bwt) exhibited significant reductions in fat absorption and improvements in fat excretion through feces. Additionally, the in vivo study revealed that RE was effective in suppressing the increase of blood glucose after starch consumption, while its effects on maltose and sucrose consumption were relatively weak.

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ENVIRONMENTAL TOXICOLOGY · 2023 · IF 4.5

Role of PLC/IP3/IP3R axis in excess molybdenum exposure induced apoptosis in duck renal tubular epithelial cells

Huiling Guo,Caiying Zhang,Wenjing Pu,Xuesheng Chu,Gang Huang,Ting Cui,Bingyan Huang,Hang Liu,Xueyan Dai

Excess molybdenum (Mo) is harmful to animals, but its nephrotoxicity has not been comprehensively explained. To appraise the influences of excess Mo on Ca homeostasis and apoptosis via PLC/IP 3 /IP 3 R axis, primary duck renal tubular epithelial cells were exposed to 480 μM and 960 μM Mo, and joint of 960 μM Mo and 10 μM 2-APB or 0.125 μM U-73122 for 12 h (U-73122 pretreated for 1 h), respectively. The data revealed that the increment of [Ca 2+ ] c induced by Mo mainly originated from intracellular Ca storage. Mo exposure reduced [Ca 2+ ] ER , elevated [Ca 2+ ] mit , [Ca 2+ ] c , and the expression of Ca homeostasis-related factors (Calpain, CaN, CRT, GRP94, GRP78 and CaMKII). 2-APB could effectively reverse subcellular Ca 2+ redistribution by inhibiting IP 3 R, which confirmed that [Ca 2+ ] c overload induced by Mo originated from ER. Additionally, PLC inhibitor U-73122 remarkably mitigated the change, and dramatically reduced the number of apoptotic cells, the expression of Bak-1, Bax, cleaved-Caspase-3/Caspase-3, and notably increased the expression of Bcl-xL, Bcl-2, and Bcl-2/Bax ratio. Overall, the results confirmed that the Ca 2+ liberation of ER via PLC/IP 3 /IP 3 R axis was the main cause of [Ca 2+ ] c overload, and then stimulated apoptosis in duck renal tubular epithelial cells.

CAS / MDL: 12054-85-2 13106-76-8
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AICHE JOURNAL · 2023 ·Vol. 70 ·期 1 ·e18239 · IF 3.7

Introduction of hydrogen bond recognition sites in ZIF-71 for effective separation of bio-diols in aqueous solutions

Jianshuang Zhang,Jinglan Wu,Meizhen Gao,Lifang Ge,Mengyao Wang,Jinxiang Dong,Qi Shi

The bio-based diols 1,3-propanediol (1,3-PDO) and 2,3-butanediol (2,3-BDO) can form strong hydrogen bonds with water, which increases the separation difficulty of diols in aqueous solutions. Herein, a series of mixed-linker ZIF-71-clnIm x samples with hydrogen bond–van der Waals (vdW) dual recognition sites have been constructed using 4-chloro-5-nitroimidazole (clnIm) linkers to substitute partially for the original 4,5-dichloroimidazole (dclIm) linkers of the ZIF-71 framework. The experimental and calculated results show that ZIF-71-clnIm x with appropriate clnIm substitution proportion ( x = 7.6 and 12.8 mol%) can strengthen the interaction between ZIF-71-clnIm x and 2,3-BDO and enhance the adsorption and mass transfer of 2,3-BDO, thus achieving the efficient separation of 2,3-BDO/1,3-PDO. Molecular simulation results further verify that 2,3-BDO can simultaneously form strong H bonds with the –NO 2 of the clnIm linker and weak vdW interactions with the –Cl of the dclIm linker, which are the mixed recognition sites for 2,3-BDO adsorption intensification in aqueous solution for ZIF-71-clnIm x .

CAS / MDL: 504-63-2
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Materials Today Communications · 2023 · IF 3.8

Fabrication of high-performance Magnéli phase Ti4O7 ceramics by in-situ hot-pressed sintering in a single step

Xinwei Geng,Yongfeng Xia,Hanqin Liang,Dongxu Yao,Yu-Ping Zeng

Magnéli phase ceramics have gained extensive attention in a variety of fields, including batteries, electrocatalysis , and wastewater treatment, due to their distinctive properties. In this study, high-performance Magnéli phase Ti 4 O 7 ceramics were synthesized by in-situ hot-pressed sintering of titanium (Ti) and titanium dioxide (TiO 2 ) in a single step. The effects of the sintering temperature and Ti content on the phase transformation and morphology of ceramics were investigated. Moreover, the mechanical properties and electrical conductivity of the samples were systematically characterized. Results show that the sample with the Ti/TiO 2 weight ratio of 0.09 sintered at 1000 °C has impressive comprehensive properties, including a high bulk density of 4.281 g·cm −1 , a mean value of flexural strength of 125.58 MPa, and an excellent conductivity of 1129 S·cm −1 . Furthermore, an evolution mechanism of the in-situ sintering for Ti/TiO 2 was discussed based on the experimental data, and the pattern of variation observed by samples can be reasonably explained.

CAS / MDL: 7440-32-6
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FOOD CHEMISTRY · 2023 · IF 8.8

N-aminomorpholine-functionalized bromine-doped carbon dots for hypochlorous acid detection in foods and imaging in live cells

Chengda Zhao,Pengxiang Yuan,Dan Wang,Shiyao Li,Huan Yao,Liu-Pan Yang,Li-Li Wang,Fangfang Du

Hypochlorous acid (HClO) is used in food preservation. However, excessive HClO can deteriorate nutritional composition of food, compromise its quality, and potentially induce various diseases. Consequently, the development of multifunctional fluorescent probes for the sensitive and selective detection of HClO is highly anticipated for food safety. In this work, we designed a nanoprobe using N -aminomorpholine (AM)-functionalized bromine-doped carbon dots (Br-CDs-AM) for sensing HClO. This nanoprobe exhibits pH stability, strong resistance to photobleaching, superior long-term photostability (12 weeks), high sensitivity (19.3 nM), and an ultrarapid response (8 s) for detecting HClO residues in food matrices with percentage recovery (96.5 %–108 %) and RSDs less than 5.34 %. In addition, extremely low cytotoxicity and outstanding biocompatibility enable the nanoprobe to be used primarily for lysosome tracking and rapidly visualizing HClO in live cells. Thus, this study provides a new pathway to design unconventional nanoprobes for food safety assessment and subcellular organelle-specific imaging HClO.

CAS / MDL: 4319-49-7 76-59-5
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SENSORS AND ACTUATORS B-CHEMICAL · 2015 · IF 4.097

An ICT-based ratiometric fluorescent probe for hydrazine detection and its application in living cells and in vivo

Xitao Xia,Fang Zeng,Peisheng Zhang,Jun Lyu,Yong Huang,Shuizhu Wu

Hydrazine is a widely used industrial material, and yet it is also a highly toxic and possibly carcinogenic substance which is likely to induce physiological dysfunction. Here, we report a ratiometric fluorescent probe (NA-N 2 H 4 ) for hydrazine detection based on the intramolecular charge transfer (ICT) mechanism. As a naphthalimide derivative with an acetate group at the 4th position of its naphthalic ring, this probe can realize both colorimetric and ratiometric detection for hydrazine. The probe NA-N 2 H 4 exhibits a very low mean detection limit of 9.40   ±   0.12   nM, which is well below the safety level (10   ppb, or 312   nM) as regulated by EPA. The probe's selectivity and anti-interference performance is found desirable, and the probe works well in quantitative detection toward hydrazine in real samples (drinking water and river water), as well as in the qualitative detection of gaseous hydrazine. Moreover, it can be employed to image hydrazine in living cells and in vivo (zebrafish).

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JOURNAL OF MOLECULAR LIQUIDS · 2023 · IF 6

Self-assembly behavior of fluorinated amphiphilic copolymer in aqueous solution and its properties in the solid film state

Yu Chen,Jiaqi Li,Liping Zhao,Huan Chen,Xia Xin,Haihua Wang,Shenshen Li,Wenbing Kang

Owing to the high electronegativity of fluorine atoms, incorporation of fluorinated moieties in a polymer can confer unique properties such as low surface energy and self-assembling ability in solution. In this study, a series of amphiphilic copolymers were prepared by radical polymerization using three monomers: 2-((2,3,3,3- tetrafluoro- 2- (1,1,2,3,3,3- hexafluoro −2- (perfluoroethoxy) propoxy) propanoyl)oxy) ethyl acrylate (FHEMA), maleic anhydride (MAH), and acrylic acid (AA). The PFHEMA block provided low surface tension, and the MAH and AA blocks (containing carboxyl) increased solubility. The properties of the polymer (PFHEMA-co-PMAH-co-PAA) can be regulated by changing the PFHEMA length. Characterization by Fourier-transform infrared spectroscopy (FTIR) and gel permeation chromatography (GPC) indicated successful polymerization (FHA01 and FHA02). When the FHEMA/MAH/AA molar ratio was 3:8:9 (FAA02), the surface tension of the hydrolyzed amphiphilic copolymers FAA02 at 300 mg·mL −1 in aqueous solution was 15.76 mN·m −1 , the lowest value due to a higher fluorine content than FAA01. FAA02 self-assembled in water to form pH-sensitive micelles with diameters greater than 140 nm. For the FAA02 film, both the F/C ratio and arrangement of fluorine-containing side chains decreased with increasing film depth. Thus, this type of fluorine-containing low surface free energy material can be developed into a high performance coating material.

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