keyword
https://read.qxmd.com/read/38627573/the-antibody-drug-conjugate-landscape
#21
Patrick Flynn, Smruthi Suryaprakash, Dan Grossman, Val Panier, John Wu
No abstract text is available yet for this article.
April 16, 2024: Nature Reviews. Drug Discovery
https://read.qxmd.com/read/38627335/cluster-triggered-self-luminescence-rapid-self-healing-and-adaptive-reprogramming-liquid-crystal-elastomers-enabled-by-dynamic-imine-bond
#22
JOURNAL ARTICLE
Qingyan Fan, Yuting Tang, Haonan Sun, Dekang Guo, Jiawei Ma, Jinbao Guo
The integration of advanced functions and diverse practical applications calls for multifunctional liquid crystal elastomers (LCEs); however, the structure-intrinsic luminescence and excellent mechanical properties of LCEs have not yet been explored. In this study, clusteroluminescence (CL)-based LCEs (CL-LCEs) were successfully fabricated without depending on large conjugated structures, thereby avoiding redundant organic synthesis and aggregation-caused quenching. The experimental and theoretical results revealed that secondary amine (-NH-) and imine (-C = N-) groups play vital roles in determining the presence of fluorescence in CL-LCEs...
April 16, 2024: Advanced Materials
https://read.qxmd.com/read/38627294/spirooxadiazoline-oxindoles-derived-from-imatinib-show-antimyeloproliferative-potential-in-k562-cells
#23
JOURNAL ARTICLE
Liviane D de Azevedo, Debora I Leite, Andressa P de Oliveira, Floriano P S Junior, Rafael F Dantas, Monica M Bastos, Nubia Boechat, Luiz C F Pimentel
Imatinib mesylate was the first representative BCR-ABL1 tyrosine kinase inhibitor (TKI) class for the treatment of chronic myeloid leukemia. Despite the revolution promoted by TKIs in the treatment of this pathology, a resistance mechanism occurs against all BCR-ABL1 inhibitors, necessitating a constant search for new therapeutic options. To develop new antimyeloproliferative substances, we applied a medicinal chemistry tool known as molecular hybridization to design 25 new substances. These compounds were synthesized and biologically evaluated against K562 cells, which express BCR-ABL1, a constitutively active tyrosine kinase enzyme, as well as in WSS-1 cells (healthy cells)...
April 16, 2024: Archiv der Pharmazie
https://read.qxmd.com/read/38627218/triflic-acid-assisted-regioselective-bromination-of-quinoxaline-derivatives-enables-a-facile-synthesis-of-polymer-ptq10
#24
JOURNAL ARTICLE
Junmo Kang, Shin Yeong Kim, Hwan Hee Jo, Kyukwan Zong
Poly[(thiophene)-alt-(6,7-difluoro-2(2-hexyldecyloxy)quinoxaline)] (PTQ10) emerges as a promising candidate for donor materials in organic solar cells (OSCs) due to its high efficiency, simplified synthesis, and cost-effectiveness. The acceptor unit of PTQ10 is derived from the alkylation of 5,8-dibromo-6,7-difluoroquinoxaline-2-ol, emphasizing the importance of its economical synthesis for commercial viability. This study investigates triflic acid-assisted regioselective bromination of quinoxaline derivatives and proposes an alternative synthetic pathway for PTQ10...
April 16, 2024: ChemSusChem
https://read.qxmd.com/read/38626834/metabolic-activation-and-cytochrome-p450-inhibition-of-piperlonguminine-mediated-by-cyp3a4
#25
JOURNAL ARTICLE
Yuqian Chi, Xiaoliang Zhu, Yaxuan Chen, Xin Li, Ziyi Jiang, Xiaoyang Jian, Mengyuan Lian, Xiaodi Wu, Lei Wang, Mengmeng Sun, Xiaowei Shi
Piperlonguminine (PLG) is a major alkaloid found in Piper longum fruits. It has been shown to possess a variety of biological activities, including anti-tumor, anti-hyperlipidemic, anti-renal fibrosis and anti-inflammatory properties. Previous studies have reported that PLG inhibits various CYP450 enzymes. The main objective of this study was to identify reactive metabolites of PLG in vitro and assess its ability to inhibit CYP450. In rat and human liver microsomal incubation systems exposed to PLG, two oxidized metabolites (M1 and M2) were detected...
April 14, 2024: International Journal of Biological Macromolecules
https://read.qxmd.com/read/38626826/large-language-model-for-horizontal-transfer-of-resistance-gene-from-resistance-gene-prevalence-detection-to-plasmid-conjugation-rate-evaluation
#26
JOURNAL ARTICLE
Jiabin Zhang, Lei Zhao, Wei Wang, Quan Zhang, Xue-Ting Wang, De-Feng Xing, Nan-Qi Ren, Duu-Jong Lee, Chuan Chen
The burgeoning issue of plasmid-mediated resistance genes (ARGs) dissemination poses a significant threat to environmental integrity. However, the prediction of ARGs prevalence is overlooked, especially for emerging ARGs that are potentially evolving gene exchange hotspot. Here, we explored to classify plasmid or chromosome sequences and detect resistance gene prevalence by using DNABERT. Initially, the DNABERT fine-tuned in plasmid and chromosome sequences followed by multilayer perceptron (MLP) classifier could achieve 0...
April 14, 2024: Science of the Total Environment
https://read.qxmd.com/read/38626743/pseudomonas-stutzeri-kc-carries-the-pdt-genes-for-carbon-tetrachloride-degradation-on-an-integrative-and-conjugative-element
#27
JOURNAL ARTICLE
Holly L Sewell, Craig S Criddle, Sung-Geun Woo, Sooyeol Kim, Jochen A Müller, Anne-Kristin Kaster
Pseudomonas stutzeri KC can rapidly degrade carbon tetrachloride (CCl4) to CO2 by a fortuitous reaction with pyridine-2,6-bis(thiocarboxylic acid), a metal chelator encoded by pdt genes. These genes were first identified after a spontaneous mutant, strain CTN1, lost the ability to degrade CCl4. Here we report the complete genome of strain KC and show that these pdt genes are located on an integrative and conjugative element (ICE), designated ICEPsstKC. Comparative genome analyses revealed homologues of pdt genes in genomes of members of other gammaproteobacterial orders...
April 16, 2024: Microbial physiology
https://read.qxmd.com/read/38626642/photodynamic-anticancer-activity-evaluation-of-novel-5-aminolevulinic-acid-and-3-hydroxypyridinone-conjugates
#28
JOURNAL ARTICLE
Jingqi Zhang, Shengli Yuan, Miaoliang Fan, Keren Wang, Jianan Guo, Anjie Zang, Jinhui Ren, Weike Su, Changjun Zhang, Yuanyuan Xie
5-Aminolevulinic acid (ALA) and its derivatives, serving as the endogenous precursor of the photosensitizer (PS) protoporphyrin IX (PpIX), successfully applied in tumor imaging and photodynamic therapy (PDT). ALA and its derivatives have been used to treat actinic keratosis (AK), basal cell carcinoma (BCC), and improve the detection of superficial bladder cancer. However, the high hydrophilicity of ALA and the conversion of PpIX to heme have limited the accumulation of PpIX, hindering the efficiency and potential application of ALA-PDT...
April 15, 2024: Bioorganic & Medicinal Chemistry
https://read.qxmd.com/read/38626556/the-orientation-of-cpg-conjugation-on-aluminum-oxyhydroxide-nanoparticles-determines-the-immunostimulatory-effects-of-combination-adjuvants
#29
JOURNAL ARTICLE
Zhihui Liang, Hang Bao, Zhiying Yao, Min Li, Chen Chen, Lei Zhang, Huiyang Wang, Yiyang Guo, Yubin Ma, Xuecheng Yang, Ge Yu, Jiancheng Zhang, Changying Xue, Bingbing Sun, Chuanbin Mao
In subunit vaccines, aluminum salts (Alum) are commonly used as adjuvants, but with limited cellular immune responses. To overcome this limitation, CpG oligodeoxynucleotides (ODNs) have been used in combination with Alum. However, current combined usage of Alum and CpG is limited to linear mixtures, and the underlying interaction mechanism between CpG and Alum is not well understood. Thus, we propose to chemically conjugate Alum nanoparticles and CpG (with 5' or 3' end exposed) to design combination adjuvants...
April 11, 2024: Biomaterials
https://read.qxmd.com/read/38626391/gold-catalyzed-reactions-of-enynals-with-alkenes-for-synthesis-binaphthyl-derivatives
#30
JOURNAL ARTICLE
Jun-Jie Hao, Juan Wu, Tao Jiang, Hejiang Luo, Rong-Tao Li
A PPh3 Au[B(C6 F5 )4 ]-catalyzed reaction of enynals and alkenes for the construction of binaphthyl derivatives was described. This transformation was achieved through o -Quinodimethane ( o -QDM) intermediate's extended conjugated addition process. The reaction has the advantages of wide substrate scopes, mild reaction conditions, high efficiency, and good scalability.
April 16, 2024: Journal of Organic Chemistry
https://read.qxmd.com/read/38626338/enhancing-glioblastoma-immunotherapy-with-integrated-chimeric-antigen-receptor-t-cells-through-the-re-education-of-tumor-associated-microglia-and-macrophages
#31
JOURNAL ARTICLE
Nianci Zhu, Sijia Chen, Yu Jin, Meng Wang, Luyao Fang, Lingjing Xue, Dexiang Hua, Ziyao Zhang, Meng Jia, Meixi Hao, Can Zhang
Glioblastoma (GBM) is an aggressive brain cancer that is highly resistant to treatment including chimeric antigen receptor (CAR)-T cells. Tumor-associated microglia and macrophages (TAMs) are major contributors to the immunosuppressive GBM microenvironment, which promotes tumor progression and treatment resistance. Hence, the modulation of TAMs is a promising strategy for improving the immunotherapeutic efficacy of CAR-T cells against GBM. Molecularly targeting drug pexidartinib (PLX) has been reported to re-educate TAMs toward the antitumorigenic M1-like phenotype...
April 16, 2024: ACS Nano
https://read.qxmd.com/read/38626322/tethered-helical-ladder-type-aromatic-lactams
#32
JOURNAL ARTICLE
Huidong Xie, Zuo Xiao, Yixiao Song, Ke Jin, Hongxing Liu, Erjun Zhou, Jing Cao, Jiangzhao Chen, Junqiao Ding, Chenyi Yi, Xingxing Shen, Chuantian Zuo, Liming Ding
Tethered nonplanar aromatics (TNAs) make up an important class of nonplanar aromatic compounds showing unique features. However, the knowledge on the synthesis, structures, and properties of TNAs remains insufficient. In this work, a new type of TNAs, the tethered aromatic lactams, is synthesized via Pd-catalyzed consecutive intramolecular direct arylations. These molecules possess a helical ladder-type conjugated system of up to 13 fused rings. The overall yields ranged from 3.4 to 4.3%. The largest of the tethered aromatic lactams, 6L-Bu-C 14 , demonstrates a guest-adaptive hosting capability of TNAs for the first time...
April 16, 2024: Journal of the American Chemical Society
https://read.qxmd.com/read/38625940/structure-and-dynamics-of-a-pentameric-kctd5-cul3-g%C3%AE-%C3%AE-e3-ubiquitin-ligase-complex
#33
JOURNAL ARTICLE
Duc Minh Nguyen, Deanna H Rath, Dominic Devost, Darlaine Pétrin, Robert Rizk, Alan X Ji, Naveen Narayanan, Darren Yong, Andrew Zhai, Douglas A Kuntz, Maha U Q Mian, Neil C Pomroy, Alexander F A Keszei, Samir Benlekbir, Mohammad T Mazhab-Jafari, John L Rubinstein, Terence E Hébert, Gilbert G Privé
Heterotrimeric G proteins can be regulated by posttranslational modifications, including ubiquitylation. KCTD5, a pentameric substrate receptor protein consisting of an N-terminal BTB domain and a C-terminal domain, engages CUL3 to form the central scaffold of a cullin-RING E3 ligase complex (CRL3KCTD5 ) that ubiquitylates Gβγ and reduces Gβγ protein levels in cells. The cryo-EM structure of a 5:5:5 KCTD5/CUL3NTD /Gβ1 γ2 assembly reveals a highly dynamic complex with rotations of over 60° between the KCTD5BTB /CUL3NTD and KCTD5CTD /Gβγ moieties of the structure...
April 23, 2024: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/38625118/monophosphoryl-lipid-a-based-adjuvant-to-promote-the-immunogenicity-of-multivalent-meningococcal-polysaccharide-conjugate-vaccines
#34
JOURNAL ARTICLE
Kishore R Alugupalli
Activation of the adaptive immune system requires the engagement of costimulatory pathways in addition to B and T cell Ag receptor signaling, and adjuvants play a central role in this process. Many Gram-negative bacterial polysaccharide vaccines, including the tetravalent meningococcal conjugate vaccines (MCV4) and typhoid Vi polysaccharide vaccines, do not incorporate adjuvants. The immunogenicity of typhoid vaccines is due to the presence of associated TLR4 ligands in these vaccines. Because the immunogenicity of MCV4 is poor and requires boosters, I hypothesized that TLR4 ligands are absent in MCV4 and that incorporation of a TLR4 ligand-based adjuvant would improve their immunogenicity...
April 1, 2024: ImmunoHorizons
https://read.qxmd.com/read/38624187/converging-optical-and-electrochemical-detection-strategies-for-multimodal-hydrazine-sensing-insights-into-substituent-driven-diverse-response
#35
JOURNAL ARTICLE
Rikitha S Fernandes, Sahil Deepak Vasistha, Ritesh Kumar Singh, Sanket Goel, Nilanjan Dey
A pair of pyrene-based chalcogen derivatives have been developed, which demonstrate multimodal ratiometric response towards hydrazine. Although these probes share a common pyrene core and differ primarily in the electronic nature of their terminal side arms, they display distinct photophysical properties. Notably, both probes undergo significant spectral changes upon the addition of hydrazine, but probe 1 exhibits a more pronounced interaction (∼5-fold fluorescence enhancement) than probe 2, attributed to the higher level of aggregation in probe 2, rendering the binding site less accessible to the incoming analyte...
April 16, 2024: Analytical Methods: Advancing Methods and Applications
https://read.qxmd.com/read/38624080/tetraanionic-oligo-dioxaborines-strongly-absorbing-near-infrared-dyes
#36
JOURNAL ARTICLE
Vladyslav Polishchuk, Andrii Kulinich, Mykola Shandura
Polymethine dyes of tetraanionic nature comprising 1,3,2-dioxaborine rings in the polymethine chain and end-groups of different electron-accepting abilities have been synthesized. They can be considered as oligomeric polymethines, where a linear conjugated π-system passes through three 1,3,2-dioxaborine units and a number of tri- and dimethine π-bridges between two end-groups. The obtained dyes exhibit near-infrared absorption and fluorescence, with molar absorption coefficients reaching as high as 564000 M-1cm-1 in DMF, rendering them among the strongest absorbers known...
April 16, 2024: Chemistry: a European Journal
https://read.qxmd.com/read/38623895/predictors-for-pathological-bone-fractures-in-children-undergoing-liver-transplantation-a-retrospective-cohort-study
#37
JOURNAL ARTICLE
Damiano Astolfi, Nathalie Rock, Dimitri Ceroni, Barbara E Wildhaber
BACKGROUND: Hepatic osteodystrophy refers to bone disorders associated with chronic liver disease, including children undergoing liver transplantation (LT). The aim of this study was to quantify the prevalence of pathological fractures (PF) in children before and after LT and to identify associated factors for their occurrence. METHODS: Children aged 0-18 years who underwent LT from 1/2005 to 12/2020 were included in this retrospective study. Data on patient demographics, types and anatomical locations of fracture and biological workups were extracted...
May 2024: Pediatric Transplantation
https://read.qxmd.com/read/38623864/two-dimensional-conjugated-metal-organic-frameworks-with-a-ring-in-ring-topology-and-high-electrical-conductance
#38
JOURNAL ARTICLE
Mingyu Yang, Yi Zhang, Renlong Zhu, Junjun Tan, Jinxin Liu, Wei Zhang, Meng Zhou, Zheng Meng
Electrically conducting two-dimensional (2D) metal-organic frameworks (MOFs) have garnered significant interest due to their remarkable structural tunability and outstanding electrical properties. However, the design and synthesis of high-performance materials face challenges due to the limited availability of specific ligands and pore structures. In this study, we have employed a novel highly branched D3h symmetrical planar conjugated ligand, dodechydroxylhexabenzotrinaphthylene (DHHBTN) to fabricate a series of 2D conductive MOFs, named M-DHHBTN (M = Co, Ni, and Cu)...
April 16, 2024: Angewandte Chemie
https://read.qxmd.com/read/38623735/doxorubicin-conjugates-a-practical-approach-for-its-cardiotoxicity-alleviation
#39
REVIEW
Abed Alqader Ibrahim, Hamdi Nsairat, Mazen Al-Sulaibi, Mohamed El-Tanani, Areej M Jaber, Zainab Lafi, Rahmeh Barakat, Duaa Azmi Abuarqoub, Ismail Sami Mahmoud, Sherine O Obare, Alaa A A Aljabali, Alaaldin M Alkilany, Walhan Alshaer
INTRODUCTION: Doxorubicin (DOX) emerges as a cornerstone in the arsenal of potent chemotherapeutic agents. Yet, the clinical deployment of DOX is tarnished by its proclivity to induce severe cardiotoxic effects, culminating in heart failure and other consequential morbidities. In response, a panoply of strategies has undergone rigorous exploration over recent decades, all aimed at attenuating DOX's cardiotoxic impact. The advent of encapsulating DOX within lipidic or polymeric nanocarriers has yielded a dual triumph, augmenting DOX's therapeutic efficacy while mitigating its deleterious side effects...
April 16, 2024: Expert Opinion on Drug Delivery
https://read.qxmd.com/read/38623732/enhanced-intramolecular-charge-transfer-and-near-infrared-fluorescence-in-4-dimethylamino-chalcone-analogues-through-extended-conjugation-synthesis-photophysical-properties-and-theoretical-modelling
#40
JOURNAL ARTICLE
Balqees S Al-Saadi, A Ramadan Ibrahim, John Husband, Ahmed H Ismail, Younis Baqi, Osama K Abou-Zied
The distinctive characteristics of near-infrared fluorescent organic molecules render them indispensable across diverse applications, from energy harvesting to bioimaging and sensing technologies. In this work, we continue our investigation on the chalcone derivative, 4-dimethylamino-2'-hydroxychalcone ( n DHC, n = 1; where n is the number of olefinic bonds), by expanding the number of central double bonds ( n = 2 (2DHC) and n = 3 (3DHC)). Additionally, we also synthesized the structurally related chalcones lacking the OH group (DC, 2DC, 3DC) in order to obtain a comprehensive understanding of their effects on the intramolecular charge transfer (ICT)...
April 16, 2024: Physical Chemistry Chemical Physics: PCCP
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