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Drosophila myosin function and muscle structure are modulated by isoform-specific amino acid residues of the relay domain 果蝇肌球蛋白的功能和肌肉结构是由接力结构域的异构体特异性氨基酸残基调节的
IF 2.2 3区 生物学
Biochemical and biophysical research communications Pub Date : 2026-04-02 Epub Date: 2026-02-10 DOI: 10.1016/j.bbrc.2026.153439
William A. Kronert, Girish C. Melkani , Anju Melkani, Sanford I. Bernstein
{"title":"Drosophila myosin function and muscle structure are modulated by isoform-specific amino acid residues of the relay domain","authors":"William A. Kronert,&nbsp;Girish C. Melkani ,&nbsp;Anju Melkani,&nbsp;Sanford I. Bernstein","doi":"10.1016/j.bbrc.2026.153439","DOIUrl":"10.1016/j.bbrc.2026.153439","url":null,"abstract":"<div><div>The relay domain of the myosin molecular motor communicates with the nucleotide binding site of the molecule, the actin-binding region, and the converter domain. Interactions between the relay and converter domains are critical for the converter to elicit movement of the lever arm, which yields the molecule's power stroke. An invariant tryptophan relay residue at the converter interface is flanked by two poorly conserved amino acids. Here we utilize mutant versions of the <em>Drosophila melanogaster</em> muscle myosin heavy chain to probe the function of these variable relay residues, residues 509 and 511. We replaced either or both poorly-conserved residues within an embryonic myosin isoform with those of the indirect flight muscle isoform. All such replacements eliminate <em>in vitro</em> actin motility, suggesting abnormal communication between the relay and converter domains that disables the power stroke. Interestingly, we found that the variations at residues 509 and 511 differentially disrupt both myosin ATPase activity and indirect flight muscle ultrastructure, with the double mutant showing the most severe effect upon ATPase activity and the least severe effect on emergent adult ultrastructure. Isoform-specific interactions may be implicated in these differential effects, as our molecular modeling at two stages of the mechanochemical cycle defined differences in contacts between the embryonic, flight muscle and chimeric 509 and 511 relay residues with a key residue in the converter domain. Overall, our studies show that two poorly conserved amino acid residues at the relay-converter interface are important to isoform-specific function of myosin and to the structural integrity of muscle.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"807 ","pages":"Article 153439"},"PeriodicalIF":2.2,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146187017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Domain adversarial gated bilinear attention networks for cross domain drug target interaction prediction 领域对抗性门控双线性注意网络跨领域药物靶标相互作用预测
IF 2.2 3区 生物学
Biochemical and biophysical research communications Pub Date : 2026-04-02 Epub Date: 2026-02-10 DOI: 10.1016/j.bbrc.2026.153448
Wenhao Lv , Qi Zhang , Liwei Liu
{"title":"Domain adversarial gated bilinear attention networks for cross domain drug target interaction prediction","authors":"Wenhao Lv ,&nbsp;Qi Zhang ,&nbsp;Liwei Liu","doi":"10.1016/j.bbrc.2026.153448","DOIUrl":"10.1016/j.bbrc.2026.153448","url":null,"abstract":"<div><div>Accurate prediction of drug-target interactions (DTIs) is crucial for accelerating drug discovery. However, current computational methods often fail to learn discriminative interaction features and generalize effectively to novel, distribution-shifted data. To address these challenges, we propose GBAN-DA (Gated Bilinear Attention Network with Domain Adaptation), a novel deep learning framework that integrates three key components: (1) a hybrid molecular encoder combining a graph convolutional network (GCN) with feature attention for drugs and a synergistic CNN-Transformer architecture for proteins; (2) a gated bilinear attention mechanism that explicitly models substructure-level interactions; and (3) a conditional domain adversarial network (CDAN) that aligns feature distributions across domains to improve generalization. Comprehensive evaluations show that GBAN-DA achieves state-of-the-art performance. On in-domain tasks, it attains AUROC/AUPRC scores of 0.964/0.950 (BindingDB) and 0.909/0.905 (BioSNAP), outperforming eight baseline models. Notably, under rigorous cold pair splits for cross-domain prediction, GBAN-DA with CDAN achieves substantial improvements of 11.9% AUROC on BindingDB and 12.9% AUROC on BioSNAP over its non-adapted variant. Case studies further validate high-confidence predictions against experimental databases for targets such as ABL1 kinase (P00519) and Cathepsin K (P43235). GBAN-DA establishes a robust framework for accurate and generalizable DTI prediction in real-world drug screening. The source code is available at <span><span>https://github.com/LWHao1999/GBAN-DA</span><svg><path></path></svg></span>.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"807 ","pages":"Article 153448"},"PeriodicalIF":2.2,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146187461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Identification of mitochondrial dysfunction-related biomarkers and immune infiltration in liver ischemia-reperfusion injury via integrated bioinformatics and machine learning 通过综合生物信息学和机器学习鉴定肝脏缺血再灌注损伤中线粒体功能障碍相关生物标志物和免疫浸润。
IF 2.2 3区 生物学
Biochemical and biophysical research communications Pub Date : 2026-04-02 Epub Date: 2026-02-10 DOI: 10.1016/j.bbrc.2026.153435
Xianxiang Chen , Yi Zhou , Zhen Zhang , Guandou Yuan , Songqing He , Fang Xiao
{"title":"Identification of mitochondrial dysfunction-related biomarkers and immune infiltration in liver ischemia-reperfusion injury via integrated bioinformatics and machine learning","authors":"Xianxiang Chen ,&nbsp;Yi Zhou ,&nbsp;Zhen Zhang ,&nbsp;Guandou Yuan ,&nbsp;Songqing He ,&nbsp;Fang Xiao","doi":"10.1016/j.bbrc.2026.153435","DOIUrl":"10.1016/j.bbrc.2026.153435","url":null,"abstract":"<div><h3>Background</h3><div>Mitochondrial dysfunction contributes to the pathogenesis of multiple diseases. This study explores the involvement of mitochondrial dysfunction-related genes (MDRGs) in liver ischemia-reperfusion injury (LIRI).</div></div><div><h3>Methods</h3><div>Differentially expressed MDRGs (DE-MDRGs) were identified using public databases. We identified key hub genes by integrating functional enrichment, protein-protein interaction (PPI) network analysis, and machine learning algorithms. These candidates underwent rigorous validation using independent cohorts, an in vivo LIRI mouse model, and computational approaches including molecular docking and dynamics simulations.</div></div><div><h3>Results</h3><div>Twelve DE-MDRGs were identified, enriched in autophagy regulation, autophagosome formation, cytokine activity, and pathways linked to neurodegenerative and graft-versus-host diseases. The MCC algorithm prioritized ten DE-MDRGs, with IL-6, HTT, and SLC19A2 consistently selected across machine learning models. ROC analysis confirmed their diagnostic accuracy. A nomogram incorporating these genes demonstrated strong predictive performance for LIRI risk. Immune profiling revealed that LIRI is characterized by an elevated presence of neutrophils, naive CD4 T cells, and activated mast cells, contrasting with a significant reduction in M2 macrophages and resting populations of mast cells and memory CD4 T cells. GSEA further revealed significant enrichments of IL-6, HTT, and SLC19A2 in pathways associated with immune responses. The differential expression of these three genes was further confirmed both in an external validation cohort and in vivo in liver tissues from the murine LIRI model. In silico screening via docking and dynamic simulations suggested that the hub genes could be effectively targeted by Curcumin, Valproic Acid, or Acetylcysteine, all of which displayed promising interaction profiles.</div></div><div><h3>Conclusion</h3><div>Our research uncovered an interaction between mitochondrial dysfunction and the immune microenvironment in LIRI. This finding could offer significant perspectives for the clinical management of LIRI through the regulation of mitochondrial activity.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"807 ","pages":"Article 153435"},"PeriodicalIF":2.2,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146177647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Wnt-dependent modulation of alveolar epithelial phenotypes and barrier function in human progenitor-like cells 人类祖样细胞中肺泡上皮表型和屏障功能的wnt依赖性调节。
IF 2.2 3区 生物学
Biochemical and biophysical research communications Pub Date : 2026-04-02 Epub Date: 2026-02-05 DOI: 10.1016/j.bbrc.2026.153384
Yu-Che Lin , Miki Igarashi , Yasuyuki Sakai , Masaki Nishikawa , Shinkichi Ishikawa , Ikuya Tanabe
{"title":"Wnt-dependent modulation of alveolar epithelial phenotypes and barrier function in human progenitor-like cells","authors":"Yu-Che Lin ,&nbsp;Miki Igarashi ,&nbsp;Yasuyuki Sakai ,&nbsp;Masaki Nishikawa ,&nbsp;Shinkichi Ishikawa ,&nbsp;Ikuya Tanabe","doi":"10.1016/j.bbrc.2026.153384","DOIUrl":"10.1016/j.bbrc.2026.153384","url":null,"abstract":"<div><div>Alveolar regeneration requires coordinated alveolar type 1 (AT1)/alveolar type 2 (AT2) responses and an intact epithelial barrier. In vitro systems, however, rarely couple lineage control with high resistance. Here we establish a concise workflow in which human AT2-like progenitors are expanded in a medium containing a small-molecule cocktail (Y-27632/A-83-01/CHIR99021; YAC), followed by air–liquid interface (ALI) culture in medium without the YAC cocktail (hereafter referred to as the YAC(−) condition). <strong>Compared with submerged culture, ALI increased AT1</strong> <em>(AQP5, AGER, and PDPN)</em> and AT2 <em>(SFTPB, SFTPC, and SFTPD)</em> markers. Within ALI, β-catenin inhibition by XAV939 elevated AT1 features while retaining AT2 protein expression, but was accompanied by reduced AT2 marker expression at the transcriptional level compared with the YAC(−) condition. Transepithelial electrical resistance entered the kΩ range by ALI day 10 and remained high across ALI conditions, with hematoxylin and eosin staining confirming a continuous single-layer epithelium. Passage reduced absolute marker levels and resistance but preserved the rank order across conditions. In scratch assays, ALI monolayers closed wounds over 24–48 h, and spatial immunofluorescence staining showed surfactant protein-C enrichment at the leading edge and podoplanin predominantly behind the front. Collectively, these findings demonstrate that β-catenin modulation within ALI biases the alveolar epithelial profile toward AT1-like features, whereas the YAC(−) condition sustains a balanced AT1/AT2 state with superior epithelial barrier performance and repair capacity. This platform provides a single-monolayer system suitable for dissecting alveolar epithelial differentiation and functional maintenance.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"807 ","pages":"Article 153384"},"PeriodicalIF":2.2,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146177696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Efficient hydrazide-mediated total synthesis of Möbius cyclotides from Viola japonica and elucidation of the antibacterial mechanism of Vija 31 酰肼介导的堇菜Möbius环肽全合成及其抑菌机理的研究
IF 2.2 3区 生物学
Biochemical and biophysical research communications Pub Date : 2026-04-02 Epub Date: 2026-02-06 DOI: 10.1016/j.bbrc.2026.153416
Binghui Ruan, Meng Liu, Jiongwen Qin, Peng Jiang, Dongting Zhangsun, Sulan Luo, Yong Wu
{"title":"Efficient hydrazide-mediated total synthesis of Möbius cyclotides from Viola japonica and elucidation of the antibacterial mechanism of Vija 31","authors":"Binghui Ruan,&nbsp;Meng Liu,&nbsp;Jiongwen Qin,&nbsp;Peng Jiang,&nbsp;Dongting Zhangsun,&nbsp;Sulan Luo,&nbsp;Yong Wu","doi":"10.1016/j.bbrc.2026.153416","DOIUrl":"10.1016/j.bbrc.2026.153416","url":null,"abstract":"<div><div>Cyclotides represent a unique family of plant-derived cyclic peptides with high structural stability and promising bioactivities, yet their pharmaceutical application is limited by low natural abundance and synthetic difficulty. Herein, we adopted an efficient hydrazide-mediated total synthesis strategy to prepare nine Möbius subfamily cyclotides from <em>Viola japonica</em> transcriptomic data. Among them, Vija 31 exhibited remarkable antibacterial potency (MIC = 2 μM against <em>Acinetobacter baumannii</em> and <em>Bacillus subtilis</em>, 64 μM against <em>Cryptococcus neoformans</em>), along with low hemolytic activity (3.36% at 128 μM). Circular dichroism spectroscopy and AlphaFold-3 modeling indicate Vija 31 adopts a compact β-sheet/β-turn conformation, which may contribute to its antibacterial activity. Scanning electron microscopy revealed Vija 31-induced bacterial membrane disruption (rupture and shrinkage), while nucleic acid and protein leakage assays confirmed concentration-dependent release of intracellular contents and time-kill kinetics demonstrated its concentration-dependent bactericidal activity. Optimization of hydrazide cyclization conditions using Vija 31 as a model further improved reaction efficiency. This work establishes a versatile and scalable route for Möbius cyclotide synthesis and identifies Vija 31 as a promising lead compound against drug-resistant bacteria.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"807 ","pages":"Article 153416"},"PeriodicalIF":2.2,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146187016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Extensive transcriptomic changes in cellular and animal models of Huntington’s disease depending on the length of CAG repeats in the exon 1 of the HTT gene 亨廷顿氏病的细胞和动物模型中广泛的转录组变化取决于HTT基因外显子1 CAG重复序列的长度
IF 2.2 3区 生物学
Biochemical and biophysical research communications Pub Date : 2026-04-01 DOI: 10.1016/j.bbrc.2026.153711
Aneta Szulc , Beata M. Walter , Lidia Gaffke , Karolina Wiśniewska , Magdalena Żabińska , Estera Rintz , Zuzanna Cyske , Michał Grabski , Oleksandr Pankiv , Magdalena Podlacha , Karolina Pierzynowska , Grzegorz Węgrzyn
{"title":"Extensive transcriptomic changes in cellular and animal models of Huntington’s disease depending on the length of CAG repeats in the exon 1 of the HTT gene","authors":"Aneta Szulc ,&nbsp;Beata M. Walter ,&nbsp;Lidia Gaffke ,&nbsp;Karolina Wiśniewska ,&nbsp;Magdalena Żabińska ,&nbsp;Estera Rintz ,&nbsp;Zuzanna Cyske ,&nbsp;Michał Grabski ,&nbsp;Oleksandr Pankiv ,&nbsp;Magdalena Podlacha ,&nbsp;Karolina Pierzynowska ,&nbsp;Grzegorz Węgrzyn","doi":"10.1016/j.bbrc.2026.153711","DOIUrl":"10.1016/j.bbrc.2026.153711","url":null,"abstract":"<div><div>Although Huntington's disease – a severe, inherited, neurodegenerative disorder – is primarily caused by a pathological variant of the <em>HTT</em> gene (encoding huntingtin protein) which is characterized by the extension of CAG repeats in the 1<sup>st</sup> exon exceeding 36 triplets, the biochemical mechanisms underlying the disease remain poorly understood. Mutant huntingtin forms toxic aggregates in cells; however, the clinical symptoms usually appear in adulthood. Recent reports suggested that somatic expansion of CAG repeats to more than 150 copies may be responsible for the pathogenicity and could explain the delayed onset of symptoms in this inherited disease. Nevertheless, it remains unclear why such an expansion occurs only in cells bearing <em>HTT</em> alleles with the original number of CAG repeats over 36. Here, we used cellular models of Huntington disease, consisting of human HEK293 cell lines with either normal (16/17) or pathogenic (41, 53, 84) numbers of CAG repeats in exon 1 of <em>HTT,</em> as well as the R6/1 mouse model. Using AlphaFold3, protein structures were predicted for the human huntingtin variants, revealing significant changes in pathogenic forms compared to the normal form. Transcriptomic analyses indicated that expression of a few thousand genes is significantly dysregulated in cells with increased CAG repeat numbers. Products of these genes are involved in various processes, such as apoptosis, autophagy, and DNA repair and recombination. Thus, we suggest that stress conditions, caused by dysregulation of cellular processes, might facilitate abnormal somatic extension of CAG repeats, contrary to cells bearing normal <em>HTT</em> alleles.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"816 ","pages":"Article 153711"},"PeriodicalIF":2.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147584856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Phototropin can trigger the chloroplast accumulation response from multiple subcellular locations in Marchantia polymorpha 趋光素可触发多形地药多个亚细胞位置的叶绿体积累反应
IF 2.2 3区 生物学
Biochemical and biophysical research communications Pub Date : 2026-03-28 DOI: 10.1016/j.bbrc.2026.153647
Mayu Hanawa , Satoyuki Hirano , Kotoko Sasaki , Hitomi Takahashi , Yutaka Kodama
{"title":"Phototropin can trigger the chloroplast accumulation response from multiple subcellular locations in Marchantia polymorpha","authors":"Mayu Hanawa ,&nbsp;Satoyuki Hirano ,&nbsp;Kotoko Sasaki ,&nbsp;Hitomi Takahashi ,&nbsp;Yutaka Kodama","doi":"10.1016/j.bbrc.2026.153647","DOIUrl":"10.1016/j.bbrc.2026.153647","url":null,"abstract":"<div><div>Chloroplasts relocate within plant cells in response to various environmental stimuli. They accumulate in areas irradiated with low light intensity to maximize capture of light energy for photosynthesis (accumulation response) and move away from areas receiving high light intensity to limit photodamage (avoidance response). These chloroplast movements are mediated by a blue-light receptor, phototropin, in a wide range of plant species. Phototropin localizes to multiple subcellular compartments, namely the plasma membrane, cytosol, and chloroplast outer membrane. However, which subcellular phototropin pool mediates chloroplast relocation remains to be determined. In our previous study, we genetically modified phototropin to target the photoreceptor to the plasma membrane (pm-phot) or the cytosol (cy-phot) in a phototropin-knockout mutant of the liverwort <em>Marchantia polymorpha</em>. Here, we generated a phototropin variant targeted to the chloroplast outer membrane (cp-phot) by adding a targeting peptide from <em>Arabidopsis thaliana</em> to the N-terminus of cy-phot. Comparisons among transgenic <em>M. polymorpha</em> lines expressing <em>pm-PHOT</em>, <em>cy-PHOT</em>, or <em>cp-PHOT</em> in a phototropin-knockout background revealed that only pm-phot mediates the avoidance response, whereas all localization variants mediate the accumulation response. We quantified the accumulation response by measuring chloroplast behavior and signal transfer rates in the transgenic lines, determining that these processes were comparable in all cells. This finding suggests that phototropin in <em>M. polymorpha</em> exhibits spatial redundancy, with the phototropin pools at the plasma membrane, cytosol, and chloroplast outer membrane all being capable of triggering the accumulation response.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"816 ","pages":"Article 153647"},"PeriodicalIF":2.2,"publicationDate":"2026-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147584853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
SLL-023ACP, a KOR/MOR dual agonist, produces potent antinociception with fewer side effects SLL-023ACP是一种KOR/MOR双激动剂,产生有效的抗孕毒作用,副作用少
IF 2.2 3区 生物学
Biochemical and biophysical research communications Pub Date : 2026-03-26 Epub Date: 2026-02-05 DOI: 10.1016/j.bbrc.2026.153411
Yi-Quan Shen , Pan-Wen Liu , Deng-Gao Zhang , Min Liu , Jia-Wen Luo , Yu-Liang Lin , Jiang-Wen Gui , Li-Jin Feng , Jing-Gen Liu , Wei Li , Yu-Jun Wang
{"title":"SLL-023ACP, a KOR/MOR dual agonist, produces potent antinociception with fewer side effects","authors":"Yi-Quan Shen ,&nbsp;Pan-Wen Liu ,&nbsp;Deng-Gao Zhang ,&nbsp;Min Liu ,&nbsp;Jia-Wen Luo ,&nbsp;Yu-Liang Lin ,&nbsp;Jiang-Wen Gui ,&nbsp;Li-Jin Feng ,&nbsp;Jing-Gen Liu ,&nbsp;Wei Li ,&nbsp;Yu-Jun Wang","doi":"10.1016/j.bbrc.2026.153411","DOIUrl":"10.1016/j.bbrc.2026.153411","url":null,"abstract":"<div><div>Opioids have served as the first-line treatment for pain management. However, their side effects such as addiction potential and constipation have limited their clinical use. Here, we characterized a novel 4,5-epoxymorphinan-based derivative SLL-023ACP, which we previously identified as a high affinity ligand towards κ-opioid receptor (KOR) and μ-opioid receptor (MOR). SLL-023ACP was identified as a full KOR agonist (EC<sub>50</sub> = 12.84 nM, E<sub>max</sub> = 85.69%) and MOR partial agonist (EC<sub>50</sub> = 31.21 nM, E<sub>max</sub> = 54.49%) <em>in vitro</em> functional cAMP inhibition assay. <em>In vivo</em>, SLL-023ACP displayed potent antinociceptive effects with ED<sub>50</sub> values of 2.6 mg/kg in the hot plate test and 0.15 mg/kg in the abdominal constriction test, exhibiting greater potency than KOR agonist U50,488H and MOR agonist Morphine. Its antinociceptive action is effectively reversed by the non-selective opioid antagonist naloxone and the MOR antagonist CTAP in the hot plate test, and by the KOR antagonist nor-BNI in the abdominal constriction test, indicating its analgesic effects was via MOR and KOR. Importantly, at analgesic doses (2.6 and 5 mg/kg), SLL-023ACP induced no conditioned place preference (CPP) and caused less constipation than morphine, although it did produce significant sedation. Taken together, these results suggest that SLL-023ACP is a potent dual KOR/MOR agonist with a favorable profile of potent analgesia with reduced addiction liability and gastrointestinal dysfunction.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"806 ","pages":"Article 153411"},"PeriodicalIF":2.2,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146122735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
ERA1 is essential for meristem growth in Arabidopsis thaliana ERA1对拟南芥分生组织生长至关重要
IF 2.2 3区 生物学
Biochemical and biophysical research communications Pub Date : 2026-03-26 Epub Date: 2026-02-05 DOI: 10.1016/j.bbrc.2026.153412
Jingwen He , Yuang Ma , Yao Jiang, Zengxiu Feng, Shiquan Yang
{"title":"ERA1 is essential for meristem growth in Arabidopsis thaliana","authors":"Jingwen He ,&nbsp;Yuang Ma ,&nbsp;Yao Jiang,&nbsp;Zengxiu Feng,&nbsp;Shiquan Yang","doi":"10.1016/j.bbrc.2026.153412","DOIUrl":"10.1016/j.bbrc.2026.153412","url":null,"abstract":"<div><div>Meristematic tissue is essential for plant growth and development, serving as a fundamental component in these processes. However, the regulatory networks and mechanism involved in its function remain inadequately understood. In this study, we investigated the role of the farnesyltransferase ERA1 in the development of plant meristematic tissues through phenotypic analysis, in situ hybridization and cell biology techniques. Our findings revealed that <em>era1-11</em> mutant exhibited retarded growth and impaired development of meristematic tissues. Moreover, the expression levels of key genes associated with meristematic tissue development, such as <em>WUS</em>, <em>CLV3</em>, <em>PLT</em>, were significantly altered in this mutant. In summary, ERA1 plays a vital role in the development of plant meristematic tissues by participating in multiple signaling pathways, thus contributing new insights into the regulatory network involved in plant meristematic tissue development.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"806 ","pages":"Article 153412"},"PeriodicalIF":2.2,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146122727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Laminarin ameliorates hepatic steatosis and upregulates hepatic SMP-30 expression in high-fat-diet-induced NAFLD mice Laminarin改善高脂肪饮食诱导的NAFLD小鼠肝脏脂肪变性和上调肝脏SMP-30表达。
IF 2.2 3区 生物学
Biochemical and biophysical research communications Pub Date : 2026-03-19 Epub Date: 2026-01-30 DOI: 10.1016/j.bbrc.2026.153359
Hyun Sook Hwang , Mo Jong Kim , Sung Eun Kim , Eun-Kyoung Choi , Ji-Won Park
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