Article
Endocrinology & Metabolism
Zhiyin Zhang, Na Chen, Nan Yin, Ruixin Liu, Yang He, Danjie Li, Muye Tong, Aibo Gao, Peng Lu, Yuxiao Zhao, Huabing Li, Junfang Zhang, Dan Zhang, Weiqiong Gu, Jie Hong, Weiqing Wang, Lu Qi, Guang Ning, Jiqiu Wang
Summary: The rs1421085 T>C variant within the FTO gene, which is a genetic risk signal for obesity, is found to be functional in vitro but lacks evidence at the organism level. In this study, researchers recapitulate the homologous human variant in mice and discover that mice carrying the C-allele exhibit increased brown fat thermogenic capacity and resistance to high-fat diet-induced adiposity. Both in vivo and in vitro data suggest that the C-allele enhances the transcription of the Fto gene in brown adipocytes, leading to stronger chromatin looping between the enhancer region and Fto promoter. Furthermore, FTO knockdown or inhibition eliminates the increased thermogenic ability of brown adipocytes carrying the C-allele. These findings establish rs1421085 T>C as a functional variant promoting brown fat thermogenesis.
Article
Chemistry, Analytical
Jonathan Martens, Rianne E. van Outersterp, Jitse Oosterhout, Christoph R. Gebhardt, Giel Berden, Udo F. H. Engelke, Ron A. Wevers, Filip Cuyckens, Jos Oomens
Summary: Infrared ion spectroscopy (IRIS) is a useful tool for identifying molecular structures detected in mass spectrometry (MS) experiments. However, coupling LC and IRIS is challenging due to the different timescales. To address this, we propose a heartcutting LC-IRIS approach using two switching valves and two sample loops as an alternative to direct coupling.
ANALYTICAL CHEMISTRY
(2023)
Review
Chemistry, Multidisciplinary
Rahul Banerjee, John D. Lipscomb
Summary: Rigorous substrate selectivity in enzyme catalysis is attributed to the favorable process of substrate binding to the enzyme active site based on complementary physiochemical characteristics. However, this selectivity becomes more difficult to rationalize for diminutive molecules with too narrow a range of physical characteristics.
ACCOUNTS OF CHEMICAL RESEARCH
(2021)
Article
Hematology
Wentao Mo, Ziqi Chen, Xiaozhe Zhang, Gang Dai, Dongwei Ma, Jiajie Pan, Xinxia Zhang, Guifu Wu, Wendong Fan
Summary: The study found that atorvastatin can decrease FTO protein expression in ECs. Silencing FTO enhances the expression of KLF2 and eNOS, but attenuates the expression of VCAM-1 and ICAM-1 induced by TNFα, as well as the adhesion of monocytes to ECs. On the contrary, overexpression of FTO increases the expression of VCAM-1 and ICAM-1, decreases the expression of KLF2 and eNOS, and weakens the induction of KLF2 and eNOS expression by atorvastatin. Further investigations reveal that FTO interacts with KLF2 and eNOS transcripts and regulates their expression in an m6A-dependent manner.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2022)
Article
Engineering, Environmental
Shuai Huang, Qingshun Dong, Yang Lu, Lian Duan, Dongdong Zhang
Summary: Organic-inorganic halide perovskites are promising materials for the next generation of photovoltaic devices due to their excellent optoelectronic characteristics. A simplified ETL-free PSC with a PPPDE interlayer has been successfully fabricated, significantly improving photovoltaic performance parameters and long-term air stability, showing potential for commercialization.
CHEMICAL ENGINEERING JOURNAL
(2021)
Review
Biochemistry & Molecular Biology
Maryam Gholamalizadeh, Samaneh Mirzaei Dahka, Farhad Vahid, Fatemeh Bourbour, Mostafa Badeli, Sepehr JavadiKooshesh, Seyed Alireza Mosavi Jarrahi, Mohammad Esmail Akbari, Ghasem Azizi Tabesh, Fatemeh Montazeri, Ayemeh Hassanpour, Saeid Doaei
Summary: This meta-analysis investigated the association between the rs9939609 FTO gene polymorphism and body fat percentage (BF%). The results showed that carriers of the A allele of FTO rs9939609 polymorphism had higher BF%.
ARCHIVES OF PHYSIOLOGY AND BIOCHEMISTRY
(2022)
Article
Cardiac & Cardiovascular Systems
Melissa A. Luse, Nenja Kruger, Miranda E. Good, Lauren A. Biwer, Vlad Serbulea, Anita Salamon, Rebecca A. Deaton, Norbert Leitinger, Axel Godecke, Brant E. Isakson
Summary: This study reveals the important role of the fat mass obesity (FTO) gene in regulating smooth muscle contractility, possibly through methylation of serum response factor (Srf).
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
(2022)
Review
Chemistry, Medicinal
Shuting Gao, Xitong Li, Miao Zhang, Ning Zhang, Ruiyong Wang, Junbiao Chang
Summary: Studies have shown a close relationship between the FTO gene and obesity and various diseases. Developing small-molecule inhibitors targeting the FTO protein not only provides a powerful tool for grasping the active site of FTO, but also lays a theoretical basis for drug design and synthesis targeting FTO protein. This review focuses on the structural characteristics of FTO inhibitors and discusses obesity and cancer caused by overexpression of the FTO gene.
FUTURE MEDICINAL CHEMISTRY
(2021)
Article
Clinical Neurology
Anil K. Chokkalla, Soomin Jeong, Suresh L. Mehta, Charles K. Davis, Kahlilia C. Morris-Blanco, Saivenkateshkomal Bathula, Simran S. Qureshi, Raghu Vemuganti
Summary: Ischemic stroke leads to increased m(6)A levels and decreased FTO expression in neurons. This study demonstrates that restoring FTO and reducing m(6)A methylation can alleviate poststroke brain damage and improve motor function, cognition, and depression-like behavior.
Review
Biochemistry & Molecular Biology
Sarah Kassem Azzam, Habiba Alsafar, Abdulrahim A. Sajini
Summary: This article reviews the role of fat mass and obesity-associated protein (FTO) in obesity and cancer. Studies have shown that FTO can promote adipogenesis and tumorigenesis, and is associated with susceptibility to obesity and various cancers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Joo-Leng Low, Weina Du, Tenzin Gocha, Gokce Oguz, Xiaoqian Zhang, Ming Wei Chen, Srdan Masirevic, Daniel Guo Rong Yim, Iain Bee Huat Tan, Adaikalavan Ramasamy, Hao Fan, Ramanuj DasGupta
Summary: A molecular docking-based approach was used to identify small molecules targeting the beta-catenin (beta-cat)-TCF4 protein-protein interaction (PPI) in the nuclear Wnt signaling pathway. In vitro experiments confirmed that GB1874 is an effective inhibitor of the Wnt pathway, impacting proliferation and stemness in colorectal cancer cells. In vivo studies demonstrated that GB1874 inhibited the growth of colorectal cancer tumor xenografts, showing potential for therapeutic development against Wnt-associated cancer indications.
Article
Pharmacology & Pharmacy
Menghan Wu, Aijun Wu, Xiangrui Zhang, Yang Li, Beibei Li, Shengzhe Jin, Qingyu Dong, Xiaoshuang Niu, Lihan Zhang, Xiaowen Zhou, Jiangfeng Du, Yahong Wu, Wenjie Zhai, Xiuman Zhou, Lu Qiu, Yanfeng Gao, Wenshan Zhao
Summary: PD-1/PD-L1 blockade has shown significant clinical outcomes in cancer treatment, but the presence of other immune checkpoints reduces its efficacy. Targeting TIM-3 with small molecule inhibitors is a promising strategy for cancer immunotherapy.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Medicine, Research & Experimental
Qi Liu, Weilin Yuan, Yuwei Yan, Bing Jin, Mengke You, Tianqi Liu, Mingchun Gao, Jin Li, Priyanka Gokulnath, Gururaja Vulugundam, Guoping Li, Bin Xu, Junjie Xiao
Summary: Muscle atrophy is a debilitating condition without effective pharmacological treatment. In this study, we developed a novel small-molecule inhibitor targeting miR-29b, which showed promising results in attenuating muscle atrophy induced by various stressors in both cell culture and animal models. This small molecule has the potential to serve as a therapeutic agent for muscle atrophy.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2023)
Article
Chemistry, Medicinal
Shifali Shishodia, Marina Demetriades, Dong Zhang, Nok Yin Tam, Pratheesh Maheswaran, Caitlin Clunie-O'Connor, Anthony Tumber, Ivanhoe K. H. Leung, Yi Min Ng, Thomas M. Leissing, Afaf H. El-Sagheer, Eidarus Salah, Tom Brown, Wei Shen Aik, Michael A. McDonough, Christopher J. Schofield
Summary: FTO catalyzes the modification of nucleic acids, including demethylation of m(6)A in mRNA, and is a proposed target for anti-cancer therapy. By using crystal structures, potent and selective FTO inhibitors were designed and synthesized, showing selectivity over other clinically targeted 2OG oxygenases. The results suggest that structure-based design can enable the development of effective FTO inhibitors for in vivo use.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Paul Tawa, Lei Zhang, Essam Metwally, Yan Hou, Mark A. McCoy, W. Michael Seganish, Rumin Zhang, Emily Frank, Payal Sheth, Jennifer Hanisak, Christopher Sondey, David Bauman, Aileen Soriano
Summary: cGMP-dependent protein kinase (PKG) is an important drug target for cardiovascular diseases. In this study, a novel series of activators were identified that can directly bind and enhance the kinase activity of PKG1. These activators mimic the effect of cGMP on PKG1 by modulating its kinetic parameters and binding affinity for cGMP. They act by binding to an allosteric site near the regulatory domain of PKG1.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Lianlian Wang, Dalong Shen, Heyao Zhang, Bingyan Mo, Jie Wu, Hongwei Hou
Summary: In this study, a series of In2S3/NU-1000 heterojunction photocatalysts were constructed to efficiently catalyze the oxidation of sulfides into sulfoxides, with the ability to detoxify sulfur mustard simulant CEES. The enhanced photocatalytic activity was attributed to the Z-scheme photocatalytic system, which showed improved light harvesting, electron-hole separation, and porosity. Mechanism studies revealed superoxide radical and singlet oxygen as the main oxidative species in the system, offering insights for designing efficient photocatalysts for detoxification purposes.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Nanoscience & Nanotechnology
Bingyan Mo, Shuwen Li, Hao Wen, Huanhuan Zhang, Heyao Zhang, Jie Wu, Baojun Li, Hongwei Hou
Summary: This study successfully synthesized a series of catalysts with regulated functional groups for hydrogen generation from ammonia borane hydrolysis, showing significantly enhanced catalytic activity. The optimized catalyst exhibited the highest catalytic activity, which is attributed to the bimolecular activation channels formed by metal nanoparticles and Ti3C2Tx-Y.
ACS APPLIED MATERIALS & INTERFACES
(2022)
Article
Chemistry, Medicinal
Qianqian Zhang, Youmei Peng, Jiao Hou, Yanhong Chen, Bingjie Liu, Pinghu Zhang, Junbiao Chang, Wenquan Yu
Summary: This research designed and synthesized a series of new O-(substituted benzyl) phosphoramidate prodrugs for the treatment of HBV infections. Prodrug 1a showed the most potent anti-HBV activity and demonstrated good tolerability in experimental animals. It exhibited significant inhibitory effect on viral replication without causing liver damage.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Aolin Jia, Shijia Huang, Wen Song, Junli Wang, Yonggang Meng, Yue Sun, Lina Xu, Henriette Laessle, Jan Jirschitzka, Jiao Hou, Tiantian Zhang, Wenquan Yu, Giuliana Hessler, Ertong Li, Shoucai Ma, Dongli Yu, Jan Gebauer, Ulrich Baumann, Xiaohui Liu, Zhifu Han, Junbiao Chang, Jane E. Parker, Jijie Chai
Summary: In this study, the researchers discovered the enzymatic activity of TIR proteins, which can catalyze the ribosylation of ADP to ATP and ADPR. This enzymatic activity plays a role in activating the immune branch in plants.
Article
Chemistry, Inorganic & Nuclear
Yujie Zhao, Yang Cui, Lixia Xie, Kangshuai Geng, Jie Wu, Xiangru Meng, Hongwei Hou
Summary: In this study, a novel metal organic framework (MOF) photocatalyst, Co-MOF, was prepared by integrating two functional organic linkers. The Co-MOF/g-C3N4 composites exhibited ultrahigh selectivity and the highest CO production rate in the photocatalytic process. This work paves the pathway for designing photocatalysts with ideal CO2 reduction performance.
INORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Manman Wang, Wenjun Ye, Nannan Sun, Wenquan Yu, Junbiao Chang
Summary: An iodine-mediated intramolecular sp3 C-H amination reaction that produces quinazolinone-fused polycyclic skeletons from 2-aminobenzamide precursors is described. The reaction is transition metal-free, has a wide substrate scope, and can be performed on a large scale. By using crude 2-aminobenzamide derivatives, the synthesis of quinazolinone-fused tetrahydroisoquinolines and Rutaecarpine derivatives from easily accessible compounds is possible without purification of the intermediates. Some of the synthesized polycyclic products exhibit inhibitory activity against Cereblon (CRBN) and show potential as anti-myeloma drugs in preliminary biological experiments.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Xiaofei Yi, Zongxiang Zhao, Manman Wang, Wenquan Yu, Junbiao Chang
Summary: In this study, an intramolecular sp3 C-H amination reaction of aniline derivatives was established using molecular iodine under transition-metal-free conditions. The reaction yielded 1,2-fused or 1,2-disubstituted benzimidazoles in an efficient and scalable fashion. This synthetic process also produced novel benzimidazolium frameworks and bioactive compounds.
Article
Chemistry, Organic
Zhongkang Yang, Manman Wang, Ruiqi Liu, Wenquan Yu, Junbiao Chang
Summary: An iodine-catalyzed aerobic alpha-hydroxylation reaction of beta-dicarbonyl compounds is developed. This synthetic method can be applied to a wide range of accessible acyclic and cyclic substrates with amide, ester, and/or ketone groups, and can be conveniently scaled up on a gram scale.
ASIAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Manman Wang, Xiaofei Yi, Wenjun Ye, Qinhao Shi, Wenquan Yu, Junbiao Chang
Summary: A new synthetic strategy for direct C(sp(3))-H amination of carbonyl compounds has been established using molecular iodine and nitrogen-directed oxidative umpolung. This approach is applicable to various carbonyl substrates, does not require transition metals, has mild reaction conditions, short reaction times, and can be used for gram-scale synthesis.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Manman Wang, Wenquan Yu, Junbiao Chang
Summary: A sustainable oxidation reaction of amines in water using environmentally friendly molecular iodine as the sole oxidant was established for the synthesis of imines and amides. This reaction features no use of transition metals, simplicity in operation, and gram-scale synthesis. It provides an easy access to imine and amide derivatives, including bioactive molecules, from readily available amine precursors.
ASIAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Jiao Hou, Youmei Peng, Bingjie Liu, Qianqian Zhang, Jian-Hua Wang, Wenquan Yu, Junbiao Chang
Summary: 2'-Deoxy-2'-β-fluoroadenosines with 4'-azido or 4'-ethynyl groups have been synthesized for the treatment of HIV-1 infection. These compounds exhibit nanomolar anti-HIV-1 activity, with the 4'-ethynyl-2-fluoroadenosine analog 1c (CL-197) being the most potent and least cytotoxic (EC50 = 0.9 nM, CC50 > 100 μM). It shows strong inhibitory activity against drug resistant and clinical HIV-1 strains. Oral administration of 1c in Beagle dogs results in high levels of the bioactive form 1c-TP in peripheral blood mononuclear cells, where it exhibits long-term intracellular retention and prevents HIV-1 infection for an extended time. 1c displays low in vivo toxicity and favorable pharmacokinetic profiles in Sprague-Dawley rats. The preclinical data support the further development of 1c as a highly potent and orally bioavailable clinical candidate for treating HIV-1 infection. Currently, CL-197 is in clinical trials in China (registration number: CXHL2200529).
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Inorganic & Nuclear
Shuwen Li, Heyao Zhang, Gaigai Wu, Jie Wu, Hongwei Hou
Summary: In this study, a new class of self-detoxifying composites, namely, HNTs@NU-912, HNTs@NU-912-I and HNTs@UiO-66-NH2, were constructed by in situ synthesis of hexanuclear zirconium cluster-based metal-organic frameworks (Zr-MOFs) NU-912, NU-912-I and UiO-66-NH2, respectively, with HNTs. These composites exhibited higher catalytic efficiency for the hydrolysis of DMNP compared to the corresponding Zr-MOFs.
DALTON TRANSACTIONS
(2023)
Article
Chemistry, Physical
Lianlian Wang, Yujie Zhao, Bin Zhang, Gaigai Wu, Jie Wu, Hongwei Hou
Summary: The combination of photocatalytic hydrogen evolution and oxidative coupling of benzylamine into imines to construct an overall photocatalytic redox system is highly desirable. A yolk-shell heterojunction Pt@UiO-66-NH2@ZnIn2S4 (Pt@UiO-66-NH2@ZIS) is synthesized and used as a dual-functional photocatalyst for C-N coupling reaction of benzylamine and proton reduction half-reaction. The unique design of Pt@UiO-66-NH2@ZIS shows significantly higher catalytic activities than individual ZnIn2S4 and UiO-66-NH2, promoting both C-N coupling reaction and H-2 evolution.
CATALYSIS SCIENCE & TECHNOLOGY
(2023)
Article
Chemistry, Inorganic & Nuclear
Bin Zhang, Qing Meng, Ying Lei, Gaigai Wu, Jinghan Xu, Xiangru Meng, Jie Wu, Hongwei Hou
Summary: This study constructs efficient Z-scheme heterojunction photocatalysts BNU-X, which enhance light capture, promote photogenerated electron-hole separation, and achieve efficient adsorption and photocatalytic degradation of TC. Moreover, this research provides possibilities for the development of porous Z-scheme photocatalysts based on photoactive MOF materials and inorganic semiconductors for the self-purification and photodegradation of organic contaminants.
DALTON TRANSACTIONS
(2023)
Article
Chemistry, Multidisciplinary
Chun-Hua Gong, Zhi-Bing Sun, Man Cao, Xi-Ming Luo, Jie Wu, Qian-You Wang, Shuang-Quan Zang, Thomas C. W. Mak
Summary: Two porphyrinic silver-chalcogenide cluster-based MOFs were achieved using a phosphate anionic template strategy. The highly photoactive organic building modules combined with Lewis acidic silver clusters allow both MOFs to function as versatile catalysts for the simultaneous degradation of sulfur mustard and nerve agent simulants.
CHEMICAL COMMUNICATIONS
(2022)
