Pub Date : 2024-11-03DOI: 10.1021/acsmedchemlett.4c0044410.1021/acsmedchemlett.4c00444
Jenson R. Feys, Kyle Edwards, Michael A. Joyce, Holly A. Saffran, Justin A. Shields, Kassandra Garcia, D. Lorne Tyrrell and Conrad Fischer*,
The main protease of SARS-CoV-2 is an essential enzyme required for polyprotein cleavage during viral replication and thus is an excellent target for development of direct-acting antiviral compounds. Continued research efforts have elucidated several peptidic small molecules like GC376, boceprevir, and nirmatrelvir with potent anticoronaviral activity bearing optimized amino acid side chain residues. To reduce synthetic complexity and cost, we used simple chemical surrogates that were commercially readily available to develop new inhibitors that mimic the potency of these drug compounds. We synthesized and tested several analogue chimeras of GC376 and boceprevir that have surrogate residues at the P1 and/or P2 position in order to further improve target binding. Both P1 variants with either a nonpolar cyclobutyl or polar thiazol-4-yl alanine resulted in low-micromolar to submicromolar Mpro inhibitors with strong antiviral activity in cell assays.
{"title":"Peptide Aldehydes Incorporating Thiazol-4-yl Alanine Are Potent In Vitro Inhibitors of SARS-CoV-2 Main Protease","authors":"Jenson R. Feys, Kyle Edwards, Michael A. Joyce, Holly A. Saffran, Justin A. Shields, Kassandra Garcia, D. Lorne Tyrrell and Conrad Fischer*, ","doi":"10.1021/acsmedchemlett.4c0044410.1021/acsmedchemlett.4c00444","DOIUrl":"https://doi.org/10.1021/acsmedchemlett.4c00444https://doi.org/10.1021/acsmedchemlett.4c00444","url":null,"abstract":"<p >The main protease of SARS-CoV-2 is an essential enzyme required for polyprotein cleavage during viral replication and thus is an excellent target for development of direct-acting antiviral compounds. Continued research efforts have elucidated several peptidic small molecules like GC376, boceprevir, and nirmatrelvir with potent anticoronaviral activity bearing optimized amino acid side chain residues. To reduce synthetic complexity and cost, we used simple chemical surrogates that were commercially readily available to develop new inhibitors that mimic the potency of these drug compounds. We synthesized and tested several analogue chimeras of GC376 and boceprevir that have surrogate residues at the P1 and/or P2 position in order to further improve target binding. Both P1 variants with either a nonpolar cyclobutyl or polar thiazol-4-yl alanine resulted in low-micromolar to submicromolar M<sup>pro</sup> inhibitors with strong antiviral activity in cell assays.</p>","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"15 11","pages":"2046–2052 2046–2052"},"PeriodicalIF":3.5,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142640749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-02DOI: 10.1016/j.ccr.2024.216285
Taiwo W. Quadri , Ekemini D. Akpan , Saheed E. Elugoke , Omar Dagdag , Nnaemeka J. Nnaji , Chandrabhan Verma , Lukman O. Olasunkanmi , Akram AlFantazi , Valentine Chikaodili Anadebe , Rakesh Chandra Barik , Eno E. Ebenso
Metallic deterioration remains a formidable challenge in numerous industrial sectors, necessitating the continuous, intense search for effective, sustainable and non-toxic chemical inhibitors. Pyrimidines and pyridazines belong to a class of heterocycles that have garnered significant attention as potential corrosion inhibitors due to their versatile chemical configuration and promising protection performances. Notably, the nitrogen atoms in the six-membered heterocyclic ring of pyrimidine (C4H4N2), pyridazine (C4H4N2), and their derivatives are well known for their capacity to form coordination bonds with metal surfaces. Pyrimidine, pyridazine, and their derivatives form corrosion-inhibitive hydrophobic layers through their adsorption on the metal surfaces. The widespread conjugation of π-electrons enhances the durability and efficacy of the hydrophobic film. They demonstrate excellent inhibition efficiencies ranging from 70 to 100 % at low concentrations (<1 mM) for different metal/electrolyte systems. This review provides an overview of the properties and application of these heterocyclic compounds in chelation and coordination. Furthermore, their potential applications as aqueous phase inhibitors for different metal/electrolyte systems were comprehensively covered. Using experimental and computational tools, emphasis was placed on the coordination chemistry of pyrimidine and pyridazine, and its adsorption behaviour against metallic degradation in diverse corrosive environments was highlighted. Finally, patent literature on the effectiveness of pyrimidine and pyridazine and future perspectives were presented.
{"title":"A critical review of coordination chemistry of pyrimidine and pyridazine compounds: Bonding, chelation and corrosion inhibition","authors":"Taiwo W. Quadri , Ekemini D. Akpan , Saheed E. Elugoke , Omar Dagdag , Nnaemeka J. Nnaji , Chandrabhan Verma , Lukman O. Olasunkanmi , Akram AlFantazi , Valentine Chikaodili Anadebe , Rakesh Chandra Barik , Eno E. Ebenso","doi":"10.1016/j.ccr.2024.216285","DOIUrl":"10.1016/j.ccr.2024.216285","url":null,"abstract":"<div><div>Metallic deterioration remains a formidable challenge in numerous industrial sectors, necessitating the continuous, intense search for effective, sustainable and non-toxic chemical inhibitors. Pyrimidines and pyridazines belong to a class of heterocycles that have garnered significant attention as potential corrosion inhibitors due to their versatile chemical configuration and promising protection performances. Notably, the nitrogen atoms in the six-membered heterocyclic ring of pyrimidine (C<sub>4</sub>H<sub>4</sub>N<sub>2</sub>), pyridazine (C<sub>4</sub>H<sub>4</sub>N<sub>2</sub>), and their derivatives are well known for their capacity to form coordination bonds with metal surfaces. Pyrimidine, pyridazine, and their derivatives form corrosion-inhibitive hydrophobic layers through their adsorption on the metal surfaces. The widespread conjugation of π-electrons enhances the durability and efficacy of the hydrophobic film. They demonstrate excellent inhibition efficiencies ranging from 70 to 100 % at low concentrations (<1 mM) for different metal/electrolyte systems. This review provides an overview of the properties and application of these heterocyclic compounds in chelation and coordination. Furthermore, their potential applications as aqueous phase inhibitors for different metal/electrolyte systems were comprehensively covered. Using experimental and computational tools, emphasis was placed on the coordination chemistry of pyrimidine and pyridazine, and its adsorption behaviour against metallic degradation in diverse corrosive environments was highlighted. Finally, patent literature on the effectiveness of pyrimidine and pyridazine and future perspectives were presented.</div></div>","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"523 ","pages":"Article 216285"},"PeriodicalIF":20.3,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-02DOI: 10.1016/j.ccr.2024.216296
Guoliang Gao , Chengzhi Xiao , Rongrong Zhang , Wangwei Chen , Conghu Liu , Guang Zhu , Bowen Sun , Lei Dai , Andreu Cabot , Zixu Sun
ZIF-67-derived materials, obtained by processes such as annealing, electrochemical reconstruction, and ion exchange, effectively overcome the limitations of low conductivity and stability that are inherent in ZIF-67, all while preserving their porous structure and high specific surface area. These derivatives not only address these issues but also offer the flexibility to modulate the component structure, rendering them promising candidates for electrocatalytic applications. This review delves into the novel application of ZIF-67 derivatives in conventional electrocatalysis, filling a crucial gap in the existing literature. The review begins by elucidating common strategies for catalyst modification, providing a foundation for understanding the subsequent sections. It then offers a detailed overview of the methods used to synthesize ZIF-67 derivatives, followed by a comprehensive examination of their application in electrocatalysis. This exploration covers a range of applications, including water splitting, CO2 reduction, fuel cells, and metal-air batteries. Furthermore, the review analyzes how the modification and synthesis of MOF derivatives impact the microstructure and catalytic performance of these materials. Finally, the review critically assesses the challenges encountered in the integration of MOF derivatives into electrocatalytic systems and offers insights into potential future research directions. By exploring these aspects, this work aims to inspire and guide researchers in overcoming existing obstacles, thereby unlocking the full potential of MOF derivatives in the field of electrocatalysis.
{"title":"ZIF-67 derivatives in electrocatalysis","authors":"Guoliang Gao , Chengzhi Xiao , Rongrong Zhang , Wangwei Chen , Conghu Liu , Guang Zhu , Bowen Sun , Lei Dai , Andreu Cabot , Zixu Sun","doi":"10.1016/j.ccr.2024.216296","DOIUrl":"10.1016/j.ccr.2024.216296","url":null,"abstract":"<div><div>ZIF-67-derived materials, obtained by processes such as annealing, electrochemical reconstruction, and ion exchange, effectively overcome the limitations of low conductivity and stability that are inherent in ZIF-67, all while preserving their porous structure and high specific surface area. These derivatives not only address these issues but also offer the flexibility to modulate the component structure, rendering them promising candidates for electrocatalytic applications. This review delves into the novel application of ZIF-67 derivatives in conventional electrocatalysis, filling a crucial gap in the existing literature. The review begins by elucidating common strategies for catalyst modification, providing a foundation for understanding the subsequent sections. It then offers a detailed overview of the methods used to synthesize ZIF-67 derivatives, followed by a comprehensive examination of their application in electrocatalysis. This exploration covers a range of applications, including water splitting, CO<sub>2</sub> reduction, fuel cells, and metal-air batteries. Furthermore, the review analyzes how the modification and synthesis of MOF derivatives impact the microstructure and catalytic performance of these materials. Finally, the review critically assesses the challenges encountered in the integration of MOF derivatives into electrocatalytic systems and offers insights into potential future research directions. By exploring these aspects, this work aims to inspire and guide researchers in overcoming existing obstacles, thereby unlocking the full potential of MOF derivatives in the field of electrocatalysis.</div></div>","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"523 ","pages":"Article 216296"},"PeriodicalIF":20.3,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Tumor metastasis is a major threat to cancer patient survival. The organ-specific niche plays a pivotal role in tumor organotropic metastasis. Fibroblasts serve as a vital component of the metastatic microenvironment, but how heterogeneous metastasis-associated fibroblasts (MAFs) promote organotropic metastasis is poorly characterized. Here, we aimed to decipher the heterogeneity of MAFs and elucidate the distinct roles of these fibroblasts in pulmonary metastasis formation in breast cancer.
Methods: Mouse models of breast cancer pulmonary metastasis were established using an in vivo selection method of repeated injections of metastatic cells purified from the mouse lung. Single-cell RNA-sequencing (scRNA-seq) was employed to investigate the heterogeneity of MAFs. Transgenic mice were used to examine the contribution of tryptophan 2,3-dioxygenase-positive matrix fibroblasts (TDO2+ MFs) in lung metastasis.
Results: We uncovered 3 subtypes of MAFs in the lung metastatic microenvironment, and their transcriptome profiles changed dynamically as lung metastasis evolved. As the predominant subtype, MFs were exclusively marked by platelet-derived growth factor receptor alpha (PDGFRA) and mainly located on the edge of the metastasis, and T cells were enriched around MFs. Notably, high MF signatures were significantly associated with poor survival in breast cancer patients. Lung metastases were markedly diminished, and the suppression of T cells was dramatically attenuated in MF-depleted experimental metastatic mouse models. We found that TDO2+ MFs controlled pulmonary metastasis by producing kynurenine (KYN), which upregulated ferritin heavy chain 1 (FTH1) level in disseminated tumor cells (DTCs), enabling DTCs to resist ferroptosis. Moreover, TDO2+ MF-secreted chemokines C-C motif chemokine ligand 8 (CCL8) and C-C motif chemokine ligand 11 (CCL11) recruited T cells. TDO2+ MF-derived KYN induced T cell dysfunction. Conditional knockout of Tdo2 in MFs diminished lung metastasis and enhanced immune activation.
Conclusions: Our study reveals crucial roles of TDO2+ MFs in promoting lung metastasis and DTCs' immune evasion in the metastatic niche. It suggests that targeting the metabolism of lung-specific stromal cells may be an effective treatment strategy for breast cancer patients with lung metastasis.
{"title":"Tryptophan 2,3-dioxygenase-positive matrix fibroblasts fuel breast cancer lung metastasis via kynurenine-mediated ferroptosis resistance of metastatic cells and T cell dysfunction.","authors":"Yongcan Liu, Shanchun Chen, Xueying Wan, Rui Wang, Haojun Luo, Chao Chang, Peijin Dai, Yubi Gan, Yuetong Guo, Yixuan Hou, Yan Sun, Yong Teng, Xiaojiang Cui, Manran Liu","doi":"10.1002/cac2.12608","DOIUrl":"10.1002/cac2.12608","url":null,"abstract":"<p><strong>Background: </strong>Tumor metastasis is a major threat to cancer patient survival. The organ-specific niche plays a pivotal role in tumor organotropic metastasis. Fibroblasts serve as a vital component of the metastatic microenvironment, but how heterogeneous metastasis-associated fibroblasts (MAFs) promote organotropic metastasis is poorly characterized. Here, we aimed to decipher the heterogeneity of MAFs and elucidate the distinct roles of these fibroblasts in pulmonary metastasis formation in breast cancer.</p><p><strong>Methods: </strong>Mouse models of breast cancer pulmonary metastasis were established using an in vivo selection method of repeated injections of metastatic cells purified from the mouse lung. Single-cell RNA-sequencing (scRNA-seq) was employed to investigate the heterogeneity of MAFs. Transgenic mice were used to examine the contribution of tryptophan 2,3-dioxygenase-positive matrix fibroblasts (TDO2<sup>+</sup> MFs) in lung metastasis.</p><p><strong>Results: </strong>We uncovered 3 subtypes of MAFs in the lung metastatic microenvironment, and their transcriptome profiles changed dynamically as lung metastasis evolved. As the predominant subtype, MFs were exclusively marked by platelet-derived growth factor receptor alpha (PDGFRA) and mainly located on the edge of the metastasis, and T cells were enriched around MFs. Notably, high MF signatures were significantly associated with poor survival in breast cancer patients. Lung metastases were markedly diminished, and the suppression of T cells was dramatically attenuated in MF-depleted experimental metastatic mouse models. We found that TDO2<sup>+</sup> MFs controlled pulmonary metastasis by producing kynurenine (KYN), which upregulated ferritin heavy chain 1 (FTH1) level in disseminated tumor cells (DTCs), enabling DTCs to resist ferroptosis. Moreover, TDO2<sup>+</sup> MF-secreted chemokines C-C motif chemokine ligand 8 (CCL8) and C-C motif chemokine ligand 11 (CCL11) recruited T cells. TDO2<sup>+</sup> MF-derived KYN induced T cell dysfunction. Conditional knockout of Tdo2 in MFs diminished lung metastasis and enhanced immune activation.</p><p><strong>Conclusions: </strong>Our study reveals crucial roles of TDO2<sup>+</sup> MFs in promoting lung metastasis and DTCs' immune evasion in the metastatic niche. It suggests that targeting the metabolism of lung-specific stromal cells may be an effective treatment strategy for breast cancer patients with lung metastasis.</p>","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":" ","pages":"1261-1286"},"PeriodicalIF":3.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1021/acsmedchemlett.4c0038210.1021/acsmedchemlett.4c00382
Hossein Shirani*, and , Seyed Majid Hashemianzadeh*,
The ANI-1x neural network potential, trained on the density functional theory data set, as a quantum-level machine learning calculation has been investigated to forecast the potential energy surfaces of the Resveratrol (3,5,4′-trihydroxy-trans-stilbene) antiparkinsonian drug in a very short computing time. A comprehensive validation of the ANI-1x deep learning technique was provided on the Resveratrol molecule using density functional theory at the wB97X/6-31G(d) level of theory. The results showcased in this study will offer significant insights into pharmaceutical computational research, medicinal chemistry, drug discovery and design, thereby making a valuable contribution.
{"title":"Machine Learning to Predict Potential Energy Surface of Resveratrol Drug: A Quantum-Level Calculation","authors":"Hossein Shirani*, and , Seyed Majid Hashemianzadeh*, ","doi":"10.1021/acsmedchemlett.4c0038210.1021/acsmedchemlett.4c00382","DOIUrl":"https://doi.org/10.1021/acsmedchemlett.4c00382https://doi.org/10.1021/acsmedchemlett.4c00382","url":null,"abstract":"<p >The ANI-1x neural network potential, trained on the density functional theory data set, as a quantum-level machine learning calculation has been investigated to forecast the potential energy surfaces of the Resveratrol (3,5,4′-trihydroxy-<i>trans</i>-stilbene) antiparkinsonian drug in a very short computing time. A comprehensive validation of the ANI-1x deep learning technique was provided on the Resveratrol molecule using density functional theory at the wB97X/6-31G(d) level of theory. The results showcased in this study will offer significant insights into pharmaceutical computational research, medicinal chemistry, drug discovery and design, thereby making a valuable contribution.</p>","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"15 11","pages":"1979–1986 1979–1986"},"PeriodicalIF":3.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142641099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.ccr.2024.216297
Ali Khorsand Zak , Abdul Manaf Hashim
Bismuth Ferrite (BiFeO₃) is a widely researched multiferroic material that exhibits ferroelectric, antiferromagnetic, and piezoelectric properties at room temperature, making it an exceptional candidate for a range of applications across multiple fields. This review explores the fundamental properties of BiFeO₃-based nanostructures, including their high Curie temperature, significant piezoelectric and photovoltaic responses, and magnetoelectric coupling. The combination of these properties enables BiFeO₃ nanostructures to be utilized in various devices, such as energy harvesting systems, optoelectronic components, and sensors. Applications in photovoltaic devices and light-emitting diodes (LEDs) further demonstrate the material's versatility and potential for innovation. Moreover, advances in thin-film fabrication techniques and interface engineering have led to improved performance and stability in BiFeO₃-based devices. Despite challenges related to carrier mobility, leakage currents, and fabrication complexity, ongoing research continues to enhance the functionality of BiFeO₃ nanostructured materials, driving their adoption in next-generation technologies. This article reviews the current state of research on BiFeO₃ nanostructures, highlighting their properties and optical applications while providing insights into their future potential in both scientific and commercial domains.
{"title":"Recent advances in BiFeO₃-based nanostructures: Properties and applications","authors":"Ali Khorsand Zak , Abdul Manaf Hashim","doi":"10.1016/j.ccr.2024.216297","DOIUrl":"10.1016/j.ccr.2024.216297","url":null,"abstract":"<div><div>Bismuth Ferrite (BiFeO₃) is a widely researched multiferroic material that exhibits ferroelectric, antiferromagnetic, and piezoelectric properties at room temperature, making it an exceptional candidate for a range of applications across multiple fields. This review explores the fundamental properties of BiFeO₃-based nanostructures, including their high Curie temperature, significant piezoelectric and photovoltaic responses, and magnetoelectric coupling. The combination of these properties enables BiFeO₃ nanostructures to be utilized in various devices, such as energy harvesting systems, optoelectronic components, and sensors. Applications in photovoltaic devices and light-emitting diodes (LEDs) further demonstrate the material's versatility and potential for innovation. Moreover, advances in thin-film fabrication techniques and interface engineering have led to improved performance and stability in BiFeO₃-based devices. Despite challenges related to carrier mobility, leakage currents, and fabrication complexity, ongoing research continues to enhance the functionality of BiFeO₃ nanostructured materials, driving their adoption in next-generation technologies. This article reviews the current state of research on BiFeO₃ nanostructures, highlighting their properties and optical applications while providing insights into their future potential in both scientific and commercial domains.</div></div>","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"523 ","pages":"Article 216297"},"PeriodicalIF":20.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142562024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The growing focus on enhancing color quality in liquid crystal displays (LCDs) and organic light-emitting diodes (OLEDs) has spurred significant advancements in color-conversion materials. Furthermore, color conversion is also important for the development and commercialization of Micro-LEDs. This article provides a comprehensive review of different types of color conversion methods as well as different types of color conversion materials. We summarize the current status of patterning process, and discuss key strategies to enhance display performance. Finally, we speculate on the future prospects and roles that color conversion will play in ultra-high-definition micro- and projection displays.
{"title":"Color-conversion displays: current status and future outlook","authors":"Guijun Li, Man-Chun Tseng, Yu Chen, Fion Sze-Yan Yeung, Hangyu He, Yuechu Cheng, Junhu Cai, Enguo Chen, Hoi-Sing Kwok","doi":"10.1038/s41377-024-01618-8","DOIUrl":"https://doi.org/10.1038/s41377-024-01618-8","url":null,"abstract":"<p>The growing focus on enhancing color quality in liquid crystal displays (LCDs) and organic light-emitting diodes (OLEDs) has spurred significant advancements in color-conversion materials. Furthermore, color conversion is also important for the development and commercialization of Micro-LEDs. This article provides a comprehensive review of different types of color conversion methods as well as different types of color conversion materials. We summarize the current status of patterning process, and discuss key strategies to enhance display performance. Finally, we speculate on the future prospects and roles that color conversion will play in ultra-high-definition micro- and projection displays.</p>","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"240 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142556334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01Epub Date: 2024-09-25DOI: 10.1002/cac2.12614
Yichuan Yuan, Hong Peng, Wei He, Yun Zheng, Jiliang Qiu, Bin Chen, Ruhai Zou, Chenwei Wang, Wan Yee Lau, Binkui Li, Yunfei Yuan
Background: The widely accepted view that portal hypertension (PHT) is a contraindication to hepatectomy for patients with hepatocellular carcinoma (HCC) is being increasingly challenged. The long-term survival outcomes and safety of partial hepatectomy versus interventional treatment using ablation with or without pre-ablation transarterial chemoembolization (TACE) in patients with HBV-related HCC within the Milan criteria and with clinically significant PHT were compared in this study.
Methods: This open-label randomized clinical trial was conducted on consecutive patients with clinically PHT and hepatitis B virus (HBV)-related HCC with tumors which were within the Milan criteria. These patients were randomized 1:1 to receive either partial hepatectomy or interventional treatment between December 2012 and June 2018. The primary endpoint was overall survival (OS); secondary endpoints included recurrence-free survival (RFS) and therapeutic safety.
Results: Each of the 2 groups had 80 patients. The 1-, 3- and 5-year OS rates in the partial hepatectomy group and the interventional treatment group were 95.0%, 86.2%, 69.5% versus 93.8%, 77.5%, 64.9%, respectively (P = 0.325). The corresponding RFS rates were 78.8%, 55.0%, 46.2% versus 71.3%, 52.5%, 45.0%, respectively (P = 0.783). The partial hepatectomy group had a higher complication rate compared to the interventional group (67.5% vs. 20%, P < 0.001). However, the differences were mainly in Clavien-Dindo Grade I complications (P < 0.001), while not significant in Grade II/III/IV/V (All P > 0.05).
Conclusions: This study shows that partial hepatectomy treatment did not meet prespecified significance for improved OS and RFS compared to interventional treatment for patients with HBV-related HCC within the Milan criteria and with clinically significant PHT. However, partial hepatectomy is still a safe procedure and should be considered as a treatment option rather than a contraindication.
{"title":"Partial hepatectomy versus interventional treatment in patients with hepatitis B virus-related hepatocellular carcinoma and clinically significant portal hypertension: a randomized comparative clinical trial.","authors":"Yichuan Yuan, Hong Peng, Wei He, Yun Zheng, Jiliang Qiu, Bin Chen, Ruhai Zou, Chenwei Wang, Wan Yee Lau, Binkui Li, Yunfei Yuan","doi":"10.1002/cac2.12614","DOIUrl":"10.1002/cac2.12614","url":null,"abstract":"<p><strong>Background: </strong>The widely accepted view that portal hypertension (PHT) is a contraindication to hepatectomy for patients with hepatocellular carcinoma (HCC) is being increasingly challenged. The long-term survival outcomes and safety of partial hepatectomy versus interventional treatment using ablation with or without pre-ablation transarterial chemoembolization (TACE) in patients with HBV-related HCC within the Milan criteria and with clinically significant PHT were compared in this study.</p><p><strong>Methods: </strong>This open-label randomized clinical trial was conducted on consecutive patients with clinically PHT and hepatitis B virus (HBV)-related HCC with tumors which were within the Milan criteria. These patients were randomized 1:1 to receive either partial hepatectomy or interventional treatment between December 2012 and June 2018. The primary endpoint was overall survival (OS); secondary endpoints included recurrence-free survival (RFS) and therapeutic safety.</p><p><strong>Results: </strong>Each of the 2 groups had 80 patients. The 1-, 3- and 5-year OS rates in the partial hepatectomy group and the interventional treatment group were 95.0%, 86.2%, 69.5% versus 93.8%, 77.5%, 64.9%, respectively (P = 0.325). The corresponding RFS rates were 78.8%, 55.0%, 46.2% versus 71.3%, 52.5%, 45.0%, respectively (P = 0.783). The partial hepatectomy group had a higher complication rate compared to the interventional group (67.5% vs. 20%, P < 0.001). However, the differences were mainly in Clavien-Dindo Grade I complications (P < 0.001), while not significant in Grade II/III/IV/V (All P > 0.05).</p><p><strong>Conclusions: </strong>This study shows that partial hepatectomy treatment did not meet prespecified significance for improved OS and RFS compared to interventional treatment for patients with HBV-related HCC within the Milan criteria and with clinically significant PHT. However, partial hepatectomy is still a safe procedure and should be considered as a treatment option rather than a contraindication.</p>","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":" ","pages":"1337-1349"},"PeriodicalIF":3.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vanessa L Kronzer, Katrina A Williamson, Keigo Hayashi, Elizabeth J Atkinson, Cynthia S Crowson, Xiaosong Wang, Jing Cui, James R Cerhan, Jennifer A Sletten, Gregory C McDermott, Elena K Joerns, Robert Vassallo, John M Davis, Jeffrey A Sparks
Objective: We aimed to identify specific genetic-respiratory disease endotypes for rheumatoid arthritis (RA) risk.
Methods: This case-control study used the Mass General Brigham (MGB) and Mayo Clinic (MC) Biobanks for discovery and replication, respectively. We matched criteria-confirmed incident RA cases to four non-RA controls on age, sex and health record history. Genetic exposures included the top 11 RA risk alleles, and a validated human leucocyte antigen (HLA) genetic risk score (GRS). We identified seven respiratory diseases by codes. Using logistic regression models adjusting for potential confounders, we estimated Rs with 95% CIs for the interactions between genetic and respiratory exposures for RA risk.
Results: We identified 653 RA cases and 2607 controls in MGB, and 428 incident RA cases and 1712 non-RA controls in MC (mean age 64, 69% female). Respiratory diseases were associated with an increased risk of RA (OR 1.34, 95% CI 1.05, 1.71). Six out of 11 non-HLA RA risk alleles interacted strongly with specific respiratory diseases for RA risk, including NFKBIE and sinusitis (OR 5.49, 95% CI 1.56, 19.4 MGB; 5.26, 95% CI 2.00, 13.86 MC) and FAM167A and acute sinusitis for seronegative RA (OR 6.00, 95% CI 2.09, 17.24 MGB; 4.90, 95% CI 1.71, 14.1 MC). The RA HLA GRS interacted synergistically with interstitial lung disease for RA risk (OR 5.41, 95% CI 2.71, 10.8 in MC), with DPB1*02:01, DRB1*16:01 and DRB1*04:04 best predicting RA (positive predictive value 61%).
Conclusion: Several genetic-respiratory disease interactions strongly drive RA onset. If confirmed, these novel associations may reflect RA endotypes that can facilitate individualised prevention, diagnosis and treatment.
目的：我们旨在确定类风湿性关节炎（RA）风险的特定遗传-呼吸系统疾病内型：我们旨在确定类风湿性关节炎（RA）风险的特定遗传-呼吸系统疾病内型：这项病例对照研究分别利用麻省总布里格姆医院（MGB）和梅奥诊所（MC）的生物库进行发现和复制。我们根据年龄、性别和健康记录史将标准确诊的RA病例与4名非RA对照者进行了配对。遗传风险包括前 11 个 RA 风险等位基因和经过验证的人类白细胞抗原（HLA）遗传风险评分（GRS）。我们通过代码确定了七种呼吸系统疾病。利用调整潜在混杂因素的逻辑回归模型，我们估算了遗传和呼吸系统暴露对 RA 风险的交互作用的 Rs 值及 95% CIs：我们在 MGB 中发现了 653 例 RA 病例和 2607 例对照，在 MC 中发现了 428 例 RA 病例和 1712 例非 RA 对照（平均年龄 64 岁，69% 为女性）。呼吸系统疾病与 RA 风险增加有关（OR 1.34，95% CI 1.05，1.71）。在 11 个非 HLA RA 风险等位基因中，有 6 个与特定呼吸系统疾病的 RA 风险有强烈的相互作用，包括 NFKBIE 与鼻窦炎（OR 5.49，95% CI 1.56，19.4 MGB；5.26，95% CI 2.00，13.86 MC），以及血清阴性 RA 的 FAM167A 与急性鼻窦炎（OR 6.00，95% CI 2.09，17.24 MGB；4.90，95% CI 1.71，14.1 MC）。RA HLA GRS与间质性肺病对RA风险有协同作用（OR 5.41，95% CI 2.71，10.8，MC），其中DPB1*02:01、DRB1*16:01和DRB1*04:04对RA的预测效果最好（阳性预测值为61%）：结论：几种遗传与呼吸系统疾病的相互作用强烈地推动了 RA 的发病。如果得到证实，这些新的关联可能反映出 RA 的内型，有助于个体化预防、诊断和治疗。
{"title":"Uncovering specific genetic-respiratory disease endotypes for rheumatoid arthritis risk.","authors":"Vanessa L Kronzer, Katrina A Williamson, Keigo Hayashi, Elizabeth J Atkinson, Cynthia S Crowson, Xiaosong Wang, Jing Cui, James R Cerhan, Jennifer A Sletten, Gregory C McDermott, Elena K Joerns, Robert Vassallo, John M Davis, Jeffrey A Sparks","doi":"10.1136/ard-2024-226391","DOIUrl":"10.1136/ard-2024-226391","url":null,"abstract":"<p><strong>Objective: </strong>We aimed to identify specific genetic-respiratory disease endotypes for rheumatoid arthritis (RA) risk.</p><p><strong>Methods: </strong>This case-control study used the Mass General Brigham (MGB) and Mayo Clinic (MC) Biobanks for discovery and replication, respectively. We matched criteria-confirmed incident RA cases to four non-RA controls on age, sex and health record history. Genetic exposures included the top 11 RA risk alleles, and a validated human leucocyte antigen (<i>HLA</i>) genetic risk score (GRS). We identified seven respiratory diseases by codes. Using logistic regression models adjusting for potential confounders, we estimated Rs with 95% CIs for the interactions between genetic and respiratory exposures for RA risk.</p><p><strong>Results: </strong>We identified 653 RA cases and 2607 controls in MGB, and 428 incident RA cases and 1712 non-RA controls in MC (mean age 64, 69% female). Respiratory diseases were associated with an increased risk of RA (OR 1.34, 95% CI 1.05, 1.71). Six out of 11 non-<i>HLA</i> RA risk alleles interacted strongly with specific respiratory diseases for RA risk, including <i>NFKBIE</i> and sinusitis (OR 5.49, 95% CI 1.56, 19.4 MGB; 5.26, 95% CI 2.00, 13.86 MC) and <i>FAM167A</i> and acute sinusitis for seronegative RA (OR 6.00, 95% CI 2.09, 17.24 MGB; 4.90, 95% CI 1.71, 14.1 MC). The RA <i>HLA</i> GRS interacted synergistically with interstitial lung disease for RA risk (OR 5.41, 95% CI 2.71, 10.8 in MC), with <i>DPB1*02:01</i>, <i>DRB1*16:01</i> and <i>DRB1*04:04</i> best predicting RA (positive predictive value 61%).</p><p><strong>Conclusion: </strong>Several genetic-respiratory disease interactions strongly drive RA onset. If confirmed, these novel associations may reflect RA endotypes that can facilitate individualised prevention, diagnosis and treatment.</p>","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":" ","pages":""},"PeriodicalIF":20.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1001/jamaneurol.2024.3766
Ronald C Petersen, Elizabeth Mormino, Julie A Schneider
{"title":"Alzheimer Disease-What's in a Name?","authors":"Ronald C Petersen, Elizabeth Mormino, Julie A Schneider","doi":"10.1001/jamaneurol.2024.3766","DOIUrl":"https://doi.org/10.1001/jamaneurol.2024.3766","url":null,"abstract":"","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":" ","pages":""},"PeriodicalIF":20.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号