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Article ; Online: A multicellular brain spheroid model for studying the mechanisms and bioeffects of ultrasound-enhanced drug penetration beyond the blood‒brain barrier.

Paranjape, Anurag N / D'Aiuto, Leonardo / Zheng, Wenxiao / Chen, Xucai / Villanueva, Flordeliza S

2024 Volume 14, Issue 1, Page(s) 1909

Abstract: The blood‒brain barrier (BBB) acts as a hindrance to drug therapy reaching the brain. With an increasing incidence of neurovascular diseases and brain cancer metastases, there is a need for an ideal in vitro model to develop novel methodologies for ... ...

Abstract	The blood‒brain barrier (BBB) acts as a hindrance to drug therapy reaching the brain. With an increasing incidence of neurovascular diseases and brain cancer metastases, there is a need for an ideal in vitro model to develop novel methodologies for enhancing drug delivery to the brain. Here, we established a multicellular human brain spheroid model that mimics the BBB both architecturally and functionally. Within the spheroids, endothelial cells and pericytes localized to the periphery, while neurons, astrocytes, and microglia were distributed throughout. Ultrasound-targeted microbubble cavitation (UTMC) is a novel noninvasive technology for enhancing endothelial drug permeability. We utilized our three-dimensional (3D) model to study the feasibility and mechanisms regulating UTMC-induced hyperpermeability. UTMC caused a significant increase in the penetration of 10 kDa Texas red dextran (TRD) into the spheroids, 100 µm beyond the BBB, without compromising cell viability. This hyperpermeability was dependent on UTMC-induced calcium (Ca
MeSH term(s)	Humans ; Blood-Brain Barrier ; Pharmaceutical Preparations ; Endothelial Cells ; Brain ; Astrocytes ; Brain Neoplasms
Chemical Substances	Pharmaceutical Preparations
Language	English
Publishing date	2024-01-22
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-50203-3
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Article ; Online: Altered gait patterns during arch important development period in children with persistent obesity: An experimental longitudinal study.

Yang, Luming / Liu, Xinye / Liu, Yuan / Zheng, Wenxiao / Wang, Wei / Yan, Shiyang

Gait & posture

2024 Volume 111, Page(s) 143–149

Abstract: Background: Obesity can cause structural changes and functional adjustments in growing children's feet. However, there is a lack of continuous observation of changes in feet in children with persistent obesity during important developmental periods. ... ...

Abstract	Background: Obesity can cause structural changes and functional adjustments in growing children's feet. However, there is a lack of continuous observation of changes in feet in children with persistent obesity during important developmental periods. This makes it challenging to provide precise preventive measures. Objective: This study aimed to investigate the effects of persistent obesity on gait patterns in children at an important stage in the formation of a robust foot arch. Methods: The Footscan® plantar pressure system was used for 3 checks over two years. A total of 372 children aged 7-8 years participated in the study, and gait data from 33 children who maintained normal weight and 26 children with persistent obesity were finally selected. Repeated measures ANOVA or Friedman's test were used for longitudinal comparisons. Independent-Sample t-tests or the Mann-Whitney-Wilcoxon tests were used for cross-sectional comparisons. Results: During the important period of development, children with persistent obesity did not exhibit a significant decrease in the arch index and had significantly higher values than the normal group in the third check. The persistently obese children showed increased load accumulation in the lateral rearfoot, first metatarsophalangeal joints, and the great toe regions. Children with persistent obesity had significantly greater medial-lateral displacements in the initial contact phase and forefoot contact phase than normal children in the first check. These differences diminished between the second and third checks. Significance: Persistent obesity during an important period of foot development leads to slow or abnormal development of arch structure and affects foot loading patterns with heel inverted and forefoot everted. Additionally, the development of gait stability is not limited by persistent obesity.
Language	English
Publishing date	2024-04-26
Publishing country	England
Document type	Journal Article
ZDB-ID	1162323-8
ISSN	1879-2219 ; 0966-6362
ISSN (online)	1879-2219
ISSN	0966-6362
DOI	10.1016/j.gaitpost.2024.04.026
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Article ; Online: Synthetic lethal combination of CHK1 and WEE1 inhibition for treatment of castration-resistant prostate cancer.

Chao, Yapeng / Chen, Yuzhou / Zheng, Wenxiao / Demanelis, Kathryn / Liu, Yu / Connelly, Jaclyn A / Wang, Hong / Li, Song / Wang, Qiming Jane

Oncogene

2024 Volume 43, Issue 11, Page(s) 789–803

Abstract: WEE1 and CHEK1 (CHK1) kinases are critical regulators of the G2/M cell cycle checkpoint and DNA damage response pathways. The WEE1 inhibitor AZD1775 and the CHK1 inhibitor SRA737 are in clinical trials for various cancers, but have not been thoroughly ... ...

Abstract	WEE1 and CHEK1 (CHK1) kinases are critical regulators of the G2/M cell cycle checkpoint and DNA damage response pathways. The WEE1 inhibitor AZD1775 and the CHK1 inhibitor SRA737 are in clinical trials for various cancers, but have not been thoroughly examined in prostate cancer, particularly castration-resistant (CRPC) and neuroendocrine prostate cancers (NEPC). Our data demonstrated elevated WEE1 and CHK1 expressions in CRPC and NEPC cell lines and patient samples. AZD1775 resulted in rapid and potent cell killing with comparable IC50s across different prostate cancer cell lines, while SRA737 displayed time-dependent progressive cell killing with 10- to 20-fold differences in IC50s. Notably, their combination synergistically reduced the viability of all CRPC cell lines and tumor spheroids in a concentration- and time-dependent manner. Importantly, in a transgenic mouse model of NEPC, both agents alone or in combination suppressed tumor growth, improved overall survival, and reduced the incidence of distant metastases, with SRA737 exhibiting remarkable single agent anticancer activity. Mechanistically, SRA737 synergized with AZD1775 by blocking AZD1775-induced feedback activation of CHK1 in prostate cancer cells, resulting in increased mitotic entry and accumulation of DNA damage. In summary, this preclinical study shows that CHK1 inhibitor SRA737 alone and its combination with AZD1775 offer potential effective treatments for CRPC and NEPC.
MeSH term(s)	Male ; Humans ; Mice ; Animals ; Cell Cycle Proteins/genetics ; Protein-Tyrosine Kinases/genetics ; Prostatic Neoplasms, Castration-Resistant/drug therapy ; Prostatic Neoplasms, Castration-Resistant/genetics ; Nuclear Proteins/metabolism ; Pyrimidinones/pharmacology ; DNA Damage ; Cell Line, Tumor
Chemical Substances	Cell Cycle Proteins ; Protein-Tyrosine Kinases (EC 2.7.10.1) ; Nuclear Proteins ; Pyrimidinones ; WEE1 protein, human (EC 2.7.10.2)
Language	English
Publishing date	2024-01-25
Publishing country	England
Document type	Journal Article
ZDB-ID	639046-8
ISSN	1476-5594 ; 0950-9232
ISSN (online)	1476-5594
ISSN	0950-9232
DOI	10.1038/s41388-024-02939-z
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Article: Reactive species conversion into 1O2 promotes substantial inhibition of chlorinated byproduct formation during electrooxidation of phenols in Cl−-laden wastewater

Zheng, Wenxiao / Chen, Yingkai / Fu, Hengyi / Yan, Zhang / Lei, Zhenchao / Duan, Weijian / Feng, Chunhua

Water research. 2022 Sept. 21,

2022

Abstract: The generation of chlorinated byproducts during the electrochemical oxidation (EO) of Cl⁻-laden wastewater is a significant concern. We aim to propose a concept of converting reactive species (e.g., reactive chlorines and HO· resulting from electrolysis) ...

Abstract	The generation of chlorinated byproducts during the electrochemical oxidation (EO) of Cl⁻-laden wastewater is a significant concern. We aim to propose a concept of converting reactive species (e.g., reactive chlorines and HO· resulting from electrolysis) into ¹O₂ via the addition of H₂O₂, which substantially alleviates chlorinated organic formation. When phenol was used as a model organic compound, the results showed that the H₂O₂-involving EO system outperformed the H₂O₂-absent system in terms of higher rate constants (5.95 × 10⁻² min⁻¹vs. 2.97 × 10⁻² min⁻¹) and a much lower accumulation of total organic chlorinated products (1.42 mg L⁻¹vs. 8.18 mg L ⁻¹) during a 60 min operation. The rate constants of disappearance of a variety of phenolic compounds were positively correlated with the Hammett constants (σ), suggesting that the reactive species preferred oxidizing phenols with electron-rich groups. After the identification of ¹O₂ that was abundant in the bulk solution with the use of electron paramagnetic resonance and computational kinetic simulation, the routes of ¹O₂ generation were revealed. Despite the consensus as to the contribution of reaction between H₂O₂ and ClO⁻ to ¹O₂ formation, we conclude that the predominant pathway is through H₂O₂ reaction with electrogenerated HO· or chlorine radicals (Cl· and Cl₂·⁻) to produce O₂·⁻, followed by self-combination. Density functional theory calculations theoretically showed the difficulty in forming chlorinated byproducts for the ¹O₂-initiated phenol oxidation in the presence of Cl⁻, which, by contrast, easily occurred for the Cl·-or HO·-initiated phenol reaction. The experiments run with real coking wastewater containing high-concentration phenols further demonstrated the superiority of the H₂O₂-involving EO system. The findings imply that this unique method for treating Cl⁻-laden organic wastewater is expected to be widely adopted for generalizing EO technology for environmental applications.
Keywords	byproducts ; chlorine ; density functional theory ; electrochemistry ; electrolysis ; electron paramagnetic resonance spectroscopy ; oxidation ; phenol ; research ; wastewater ; water
Language	English
Dates of publication	2022-0921
Publishing place	Elsevier Ltd
Document type	Article
Note	Pre-press version
ZDB-ID	202613-2
ISSN	1879-2448 ; 0043-1354
ISSN (online)	1879-2448
ISSN	0043-1354
DOI	10.1016/j.watres.2022.119143
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Article ; Online: A Bipolar Membrane-Integrated Electrochlorination Process for Highly Efficient Ammonium Removal in Mature Landfill Leachate: The Importance of ClO

Kuang, Wenjie / Yan, Zhang / Chen, Jinxiu / Ling, Xiaotang / Zheng, Wenxiao / Huang, Weijun / Feng, Chunhua

Environmental science & technology

2022 Volume 57, Issue 47, Page(s) 18538–18549

Abstract: Electrochemical oxidation has been demonstrated to be a useful method for removing biorefractory organic pollutants in mature landfill leachate but suffers from low efficiency in eliminating ammonium because of its resistance to being oxidized by ... ...

Abstract	Electrochemical oxidation has been demonstrated to be a useful method for removing biorefractory organic pollutants in mature landfill leachate but suffers from low efficiency in eliminating ammonium because of its resistance to being oxidized by HO
MeSH term(s)	Ammonium Compounds ; Water Pollutants, Chemical ; Wastewater ; Organic Chemicals ; Nitrates ; Oxidation-Reduction ; Nitrogen
Chemical Substances	Ammonium Compounds ; Water Pollutants, Chemical ; Wastewater ; Organic Chemicals ; Nitrates ; Nitrogen (N762921K75)
Language	English
Publishing date	2022-10-14
Publishing country	United States
Document type	Journal Article
ISSN	1520-5851
ISSN (online)	1520-5851
DOI	10.1021/acs.est.2c05735
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Article ; Online: Reactive species conversion into

Zheng, Wenxiao / Chen, Yingkai / Fu, Hengyi / Yan, Zhang / Lei, Zhenchao / Duan, Weijian / Feng, Chunhua

Water research

2022 Volume 225, Page(s) 119143

Abstract: The generation of chlorinated byproducts during the electrochemical oxidation (EO) of ... ...

Abstract	The generation of chlorinated byproducts during the electrochemical oxidation (EO) of Cl
MeSH term(s)	Waste Water/chemistry ; Chlorine/chemistry ; Water Purification/methods ; Phenol/chemistry ; Hydrogen Peroxide/chemistry ; Phenols ; Halogens/chemistry ; Oxidation-Reduction ; Chlorides ; Water Pollutants, Chemical/chemistry ; Ultraviolet Rays
Chemical Substances	Waste Water ; Chlorine (4R7X1O2820) ; Phenol (339NCG44TV) ; Hydrogen Peroxide (BBX060AN9V) ; Phenols ; Halogens ; Chlorides ; Water Pollutants, Chemical
Language	English
Publishing date	2022-09-24
Publishing country	England
Document type	Journal Article
ZDB-ID	202613-2
ISSN	1879-2448 ; 0043-1354
ISSN (online)	1879-2448
ISSN	0043-1354
DOI	10.1016/j.watres.2022.119143
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Article ; Online: Boosting Ammonium Oxidation in Wastewater by the BiOCl-Functionalized Anode.

Yan, Zhang / Kuang, Wenjian / Lei, Yu / Zheng, Wenxiao / Fu, Hengyi / Li, Han / Lei, Zhenchao / Yang, Xin / Zhu, Shishu / Feng, Chunhua

Environmental science & technology

2023 Volume 57, Issue 49, Page(s) 20915–20928

Abstract: Mixed metal oxide (MMO) anodes are commonly used for electrochlorination of ammonium ( ... ...

Abstract	Mixed metal oxide (MMO) anodes are commonly used for electrochlorination of ammonium (NH
MeSH term(s)	Wastewater ; Ammonium Compounds ; Chlorine ; Oxidation-Reduction ; Oxides/chemistry ; Electrodes ; Water Pollutants, Chemical/analysis ; Chlorides
Chemical Substances	Wastewater ; Ammonium Compounds ; Chlorine (4R7X1O2820) ; Oxides ; Water Pollutants, Chemical ; Chlorides
Language	English
Publishing date	2023-11-28
Publishing country	United States
Document type	Journal Article
ISSN	1520-5851
ISSN (online)	1520-5851
DOI	10.1021/acs.est.3c06326
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Article: Synthetic lethal combination of CHK1 and WEE1 inhibition for treatment of castration-resistant prostate cancer.

Wang, Qiming / Chao, Yapeng / Chen, Yuzhou / Zheng, Wenxiao / Demanelis, Kathryn / Liu, Yu / Connelly, Jaclyn / Wang, Hong

Research square

2023

Abstract	WEE1 and CHEK1 (CHK1) kinases are critical regulators of the G2/M cell cycle checkpoint and DNA damage response pathways. The WEE1 inhibitor AZD1775 and the CHK1 inhibitor SRA737 are in clinical trials for various cancers, but have not been examined in prostate cancer, particularly castration-resistant (CRPC) and neuroendocrine prostate cancers (NEPC). Our data demonstrated elevated WEE1 and CHK1 expressions in CRPC/NEPC cell lines and patient samples. AZD1775 resulted in rapid and potent cell killing with comparable IC50s across different prostate cancer cell lines, while SRA737 displayed time-dependent progressive cell killing with 10- to 20-fold differences in IC50s. Notably, their combination synergistically reduced the viability of all CRPC cell lines and tumor spheroids in a concentration- and time-dependent manner. Importantly, in a transgenic mouse model of NEPC, both agents alone or in combination suppressed tumor growth, improved overall survival, and reduced the incidence of distant metastases, with SRA737 exhibiting remarkable single agent anticancer activity. Mechanistically, SRA737 synergized with AZD1775 by blocking AZD1775-induced feedback activation of CHK1 in prostate cancer cells, resulting in increased mitotic entry and accumulation of DNA damage. In summary, this preclinical study shows that CHK1 inhibitor SRA737 alone and its combination with AZD1775 offer potential effective treatments for CRPC and NEPC.
Language	English
Publishing date	2023-11-08
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-3564450/v1
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Article: Minimizing toxic chlorinated byproducts during electrochemical oxidation of Ni-EDTA: Importance of active chlorine-triggered Fe(II) transition to Fe(IV)

Xu, Haolin / Chen, Rundong / Liang, Sheng / Lei, Zhenchao / Zheng, Wenxiao / Yan, Zhang / Cao, Jianxin / Wei, Chaohai / Feng, Chunhua

Water research. 2022 July 01, v. 219

2022

Abstract: The formation of chlorinated byproducts represents a significant threat to the quality of the effluent treated using electrochemical advanced oxidation processes (EAOPs), thus spurring investigation into alleviating their production. This study presents ... ...

Abstract	The formation of chlorinated byproducts represents a significant threat to the quality of the effluent treated using electrochemical advanced oxidation processes (EAOPs), thus spurring investigation into alleviating their production. This study presents a new strategy to minimize the release of chlorinated intermediates during the electrochemical oxidation of Ni-EDTA by establishing a dual mixed metal oxide (MMO)/Fe anode system. The results indicate that the dual-anode system achieved a substantially higher rate (0.141 min⁻¹) of Ni-EDTA destruction and accordingly allowed a more pronounced removal of aqueous Ni (from 39.85 to 0.63 mg L⁻¹) after alkaline precipitation, compared with its single MMO anode (0.017 min⁻¹ of Ni-EDTA removal, with 14.38 mg L⁻¹ Ni remaining) and single Fe anode (insignificant Ni-EDTA removal, with 38.37 mg L⁻¹ Ni remaining) counterparts. Compared to reactive chlorine species (RCS) produced from the single MMO anode system, Fe(IV) was in situ generated from the dual-anode system and was predominantly responsible for the attenuation of chlorinated byproducts and thus the decrease in the acute toxicity of the treated solution (evaluated using luminescent bacteria). The Fe(IV)-dominated dual-anode system also exhibited superior performance in removing multiple pollutants (including organic ligands, Ni, and phosphite) in the real electroless plating effluent. The findings suggest that the strategy for Fe(II) transition to Fe(IV) by active chlorine paves a new avenue for yielding less chlorinated products with lower toxicity when EAOPs are used to treat chloride-containing organic wastewater.
Keywords	acute toxicity ; anodes ; chlorine ; electrochemistry ; ligands ; luminescence ; oxidation ; research ; wastewater ; water
Language	English
Dates of publication	2022-0701
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	202613-2
ISSN	1879-2448 ; 0043-1354
ISSN (online)	1879-2448
ISSN	0043-1354
DOI	10.1016/j.watres.2022.118548
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Article: Boosting the oxidative capacity of the Fe(0)/O2 system via an air-breathing cathode

Lei, Zhenchao / Huang, Ziyuan / Lin, Yimin / Liu, Yuwei / Yan, Zhang / Zheng, Wenxiao / Ma, Huanxin / Dang, Zhi / Feng, Chunhua

Journal of hazardous materials. 2022 Sept. 15, v. 438

2022

Abstract: The corrosion of Fe(0) in the presence of O₂ in nature can lead to the oxidation of organic compounds, but the efficiency is very limited. Herein, attempts were made to establish a galvanic system that separates the anodic Fe(0) oxidation reaction and ... ...

Abstract	The corrosion of Fe(0) in the presence of O₂ in nature can lead to the oxidation of organic compounds, but the efficiency is very limited. Herein, attempts were made to establish a galvanic system that separates the anodic Fe(0) oxidation reaction and the cathodic O₂ reduction reaction using an air-breathing cathode. Compared with the chemical Fe(0)/O₂ system, it exhibited a substantially higher capability of destroying a variety of pollutants, such as organic dyes (12 types), phenol, nitrobenzene, acetaminophen, phenol, and ethylenediaminetetraacetic acid. The degradation rate constant of a model dye (i.e., Rhodamine B) increased from 0.047 min⁻¹ (chemical) to 1.412 min⁻¹ (galvanic) under the passive air-breathing condition. The electric circuit design promoted Fe(0) dissolution to Fe(II) and triggered electron transfer that drives O₂ reduction to H₂O₂, two important species responsible for the generation of HO• at high abundance. In addition, the galvanic Fe(0)/O₂ system produces electricity while destroying pollutants. Tests with real Ni plating wastewater further demonstrated the capability of the system to oxidize complexed organics and phosphite. This study provides a new strategy for boosting the oxidative capacity of the Fe(0)/O₂ system, which shows promise for acid wastewater treatment.
Keywords	EDTA (chelating agent) ; acetaminophen ; cathodes ; corrosion ; dyes ; electricity ; electron transfer ; electronic circuits ; nitrobenzenes ; oxidation ; phenol ; rhodamines ; wastewater ; wastewater treatment
Language	English
Dates of publication	2022-0915
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	1491302-1
ISSN	1873-3336 ; 0304-3894
ISSN (online)	1873-3336
ISSN	0304-3894
DOI	10.1016/j.jhazmat.2022.129552
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