toxins

毒素
  • 文章类型: Journal Article
    这项综合研究旨在确定营养化合物的水平(20种氨基酸,11酚酸,和8种维生素)和有害化合物(14种霉菌毒素)在来自25个国家的10种常规和生态坚果中。此外,对真菌毒素进行慢性和急性毒理学风险评估.使用LC-MS/MS测定检查的成分。生态松子显示出最高水平的氨基酸(233.87gkg-1)与常规(207gkg-1)相比,山核桃酚酸(生态为816.6mgkg-1,常规为761mgkg-1),而开心果维生素(生态中的3471.4mgkg-1和常规中的3098.4mgkg-1)。在常规花生(54μgkg-1)和核桃(49.9μgkg-1)中确定了霉菌毒素的浓度增加。儿童是常规开心果中HT-2毒素急性中毒的最多人群(20.66%ARfD)。结果证实了生态坚果的营养重要性,并强调了持续筛选霉菌毒素的必要性。
    This comprehensive study aimed to determine the level of nutritional compounds (20 amino acids, 11 phenolic acids, and 8 vitamins) and hazard compounds (14 mycotoxins) in ten types of conventional and ecological nuts from 25 countries. Moreover, chronic and acute toxicological risk assessment of mycotoxins was performed. Examined constituents were determined using LC-MS/MS. Ecological pine nuts showed the highest level of amino acids (233.87 g kg-1) compared to conventional (207 g kg-1), pecans-phenolic acids (816.6 mg kg-1 in ecological and 761 mg kg-1 in conventional), while pistachios-vitamins (3471.4 mg kg-1 in ecological and 3098.4 mg kg-1 in conventional). Increased concentration of mycotoxins was determined in conventional peanuts (54 μg kg-1) and walnuts (49.9 μg kg-1). Children were the most exposed population to acute intoxication with HT-2 toxin in conventional pistachios (20.66% ARfD). The results confirmed the nutritional importance of ecological nuts and emphasized the need for continuous screening of mycotoxins.
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  • 文章类型: Journal Article
    VI型分泌系统(T6SS)是一种多组分器官,存在于许多革兰氏阴性细菌中,可以抑制各种生态位的细菌猎物。铜绿假单胞菌组装其三个T6SS中的一个(H1-T6SS)以响应来自邻近竞争细菌的攻击。令人惊讶的是,H1-T6SS的重复组装,称为决斗,在没有攻击者菌株的情况下,在单一文化中进行了描述;然而,潜在的机制是未知的。这里,我们探讨了铜绿假单胞菌H2-T6SS在触发H1-T6SS组装中的作用。我们表明,铜绿假单胞菌中的H2-T6SS失活导致H1-T6SS决斗显着减少,并且H2-T6SS活性直接触发H1-T6SS的报复。种内竞争实验表明,在非免疫猎物细胞中消除H2-T6SS可保护H1-T6SS。此外,我们表明,H1-T6SS反应的触发独立于H2-T6SS的表征脂肪酶效应子,以及鲍氏不动杆菌和霍乱弧菌。我们的结果表明,H1-T6SS响应H2-T6SS在铜绿假单胞菌可以影响种内竞争,特别是当H1-T6SS效应子免疫对在菌株之间不同时,并可以确定多菌株定植的结果。机会致病菌铜绿假单胞菌有三种不同的VI型分泌系统(H1、H2和H3-T6SS),可以转运毒素,这些毒素可以抑制细菌竞争者或对真核宿主细胞造成损害。与其他革兰氏阴性细菌中不受调节的T6SS组装不同,铜绿假单胞菌中的H1-T6SS作为对来自邻近细菌细胞的各种细胞损伤攻击的响应而被精确地组装。令人惊讶的是,观察到邻近的铜绿假单胞菌细胞重复地相互组装它们的H1-T6SS。引发姐妹细胞之间这种“决斗”行为的机制尚不清楚。在这份报告中,我们使用了显微镜的组合,遗传和种内竞争实验表明H2-T6SS启动H1-T6SS决斗。我们的研究强调了铜绿假单胞菌不同T6SS簇之间的相互作用,这可能会影响各种生态环境中的多菌株竞争结果,例如生物膜的形成和囊性纤维化肺的定植。
    The Type VI secretion system (T6SS) is a multicomponent apparatus, present in many Gram-negative bacteria, which can inhibit bacterial prey in various ecological niches. Pseudomonas aeruginosa assembles one of its three T6SS (H1-T6SS) to respond to attacks from adjacent competing bacteria. Surprisingly, repeated assemblies of the H1-T6SS, termed dueling, were described in a monoculture in the absence of an attacker strain; however, the underlying mechanism was unknown. Here, we explored the role of H2-T6SS of P. aeruginosa in triggering H1-T6SS assembly. We show that H2-T6SS inactivation in P. aeruginosa causes a significant reduction in H1-T6SS dueling and that H2-T6SS activity directly triggers retaliation by the H1-T6SS. Intraspecific competition experiments revealed that elimination of H2-T6SS in non-immune prey cells conferred protection from H1-T6SS. Moreover, we show that the H1-T6SS response is triggered independently of the characterized lipase effectors of the H2-T6SS, as well as those of Acinetobacter baylyi and Vibrio cholerae. Our results suggest that H1-T6SS response to H2-T6SS in P. aeruginosa can impact intraspecific competition, particularly when the H1-T6SS effector-immunity pairs differ between strains, and could determine the outcome of multistrain colonization.IMPORTANCEThe opportunistic pathogen Pseudomonas aeruginosa harbors three different Type VI secretion systems (H1, H2, and H3-T6SS), which can translocate toxins that can inhibit bacterial competitors or inflict damage to eukaryotic host cells. Unlike the unregulated T6SS assembly in other Gram-negative bacteria, the H1-T6SS in P. aeruginosa is precisely assembled as a response to various cell damaging attacks from neighboring bacterial cells. Surprisingly, it was observed that neighboring P. aeruginosa cells repeatedly assemble their H1-T6SS toward each other. Mechanisms triggering this \"dueling\" behavior between sister cells were unknown. In this report, we used a combination of microscopy, genetic and intraspecific competition experiments to show that H2-T6SS initiates H1-T6SS dueling. Our study highlights the interplay between different T6SS clusters in P. aeruginosa, which may influence the outcomes of multistrain competition in various ecological settings such as biofilm formation and colonization of cystic fibrosis lungs.
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  • 文章类型: Journal Article
    Acute kidney injury (AKI) remains a global public health problem with high incidence, high mortality rates, expensive medical costs, and limited treatment options. AKI can further progress to chronic kidney disease (CKD) and eventually end-stage renal disease (ESRD). Previous studies have shown that trauma, adverse drug reactions, surgery, and other factors are closely associated with AKI. With further in-depth exploration, the role of gut microbiota in AKI is gradually revealed. After AKI occurs, there are changes in the composition of gut microbiota, leading to disruption of the intestinal barrier, intestinal immune response, and bacterial translocation. Meanwhile, metabolites of gut microbiota can exacerbate the progression of AKI. Therefore, elucidating the specific mechanisms by which gut microbiota is involved in the occurrence and development of AKI can provide new insights from the perspective of intestinal microbiota for the prevention and treatment of AKI.
    急性肾损伤(acute kidney injury,AKI)是一个全球性的公共卫生问题,其发病率和病死率高、医疗费用昂贵且治疗手段有限。AKI可进一步转变为慢性肾脏病(chronic kidney disease,CKD),最终进展为终末期肾病(end-stage renal disease,ESRD)。既往研究表明,创伤、药物的不良反应、手术等与AKI密切相关。随着进一步的深入探索,肠道菌群在AKI中的作用逐渐被揭示。AKI发生后,肠道菌群组成改变,肠道屏障破坏引发肠道免疫以及肠道细菌易位。同时,肠道菌群的代谢产物又可以加剧AKI的进展。因此,阐述肠道菌群参与AKI发生和发展的具体机制,有助于从肠道微生物角度为AKI的防治提供新思路。.
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  • 文章类型: Journal Article
    这封信强调了软体动物毒素肽作为心血管疾病(CVD)创新治疗的潜力。考虑到心血管疾病发病率的上升和目前治疗方法的局限性,新的方法是必不可少的。软体动物产生生物活性肽,显示有希望的抗高血压,抗血栓,和心脏保护特性。例如,来自海洋蜗牛的螺毒素抑制电压门控钙通道,表明它们作为抗高血压药的潜力。肽工程的进步可以解决与生物利用度和稳定性相关的挑战。需要更多的研究和合作来研究这些肽的机制,治疗潜力,和安全,这可能会导致开创性的CVD治疗。
    This letter emphasizes the potential of mollusc toxin peptides as innovative treatments for cardiovascular diseases (CVDs). Given the rising incidence of CVDs and the limitations of current therapies, new approaches are essential. Molluscs produce bioactive peptides that show promising anti-hypertensive, anti-thrombotic, and cardio-protective properties. For example, conotoxins from marine snails inhibit voltage-gated calcium channels, indicating their potential as anti-hypertensive agents. Advancements in peptide engineering can address challenges related to bioavailability and stability. Increased research and collaboration are needed to investigate these peptides\' mechanisms, therapeutic potential, and safety, which could lead to groundbreaking CVD treatments.
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  • 文章类型: Journal Article
    产气荚膜梭菌是一种机会性细菌,可引起人类和动物的肠道疾病。这项研究旨在评估产气荚膜梭菌的频率以及在Boyacá部门有或没有胃肠道症状的个体的粪便样本中毒素编码基因的存在。哥伦比亚。此外,分析了与携带和疾病发展相关的危险因素。使用基于靶向16S-rRNA和α毒素(cpa)基因的特异性聚合酶链反应(PCR)的分子测试分析了总共114个粪便样品。对于PCR检测结果为阳性的个体,将粪便样品在乳糖亚硫酸环丝氨酸(TSC)琼脂上培养。根据表型特征选择两到五个菌落形成单位,产生56个细菌分离株。然后分析这些分离株的与胃肠疾病相关的毒素编码基因。此外,我们还分析了77例患者的社会人口统计学和临床数据.产气荚膜梭菌的总频率为19.3%(n=22/114)。有临床数据的77例个体中的检测频率在有症状个体中为16.6%(n=5/30),在无症状个体中为21.2%(n=10/47)。获得的所有56个分离株都带有cpa基因,而cpb2在10.7%(n=6/56)中存在;未检测到cpe和cpb基因。值得注意的是,糖尿病和自身免疫性疾病与产气荚膜梭菌检出风险增加显著相关(校正OR8.41:95%CI1.32-35.89).这项研究强调了无症状个体与有症状个体相比,产气荚膜梭菌的频率升高和cpb2基因的存在。这些发现提供了在微观地理水平上对产气荚膜梭菌的分布和毒力因子的见解。这些信息支持需要根据当地特点制定量身定制的预防策略,以促进基于分子流行病学的积极监测计划。
    Clostridium perfringens is an opportunistic bacterium that causes intestinal diseases in both humans and animals. This study aimed to assess the frequency of C. perfringens and the presence of toxin-encoding genes in fecal samples from individuals with or without gastrointestinal symptoms in the Department of Boyacá, Colombia. Additionally, risk factors associated with carriage and disease development were analyzed. A total of 114 stool samples were analyzed using a molecular test based on specific polymerase chain reaction (PCR) targeting 16S-rRNA and alpha toxin (cpa) genes. For individuals with a positive result for the PCR test, stool samples were cultured on Tryptose Sulfite Cycloserine (TSC) agar. Two to five colonies forming units were selected based on phenotypic characteristics, resulting in 56 bacterial isolates. These isolates were then analyzed for toxin-coding genes associated with gastrointestinal diseases. In addition, sociodemographic and clinical data from 77 individuals were also analyzed. The overall frequency of C. perfringens was 19.3% (n = 22/114). The detection frequency in 77 individuals with clinical data was 16.6% (n = 5/30) among symptomatic individuals and 21.2% (n = 10/47) among asymptomatic individuals. All 56 isolates obtained carried the cpa gene, while cpb2 was present in 10.7% (n = 6/56); cpe and cpb genes were not detected. Notably, diabetes and autoimmune diseases are significantly associated with an increased risk of C. perfringens detection (adjusted OR 8.41: 95% CI 1.32-35.89). This study highlights an elevated frequency of C. perfringens and the presence of the cpb2 gene in asymptomatic individuals compared with their symptomatic counterparts. These findings offer insights into the distribution and virulence factors of C. perfringens at a micro-geographical level. This information supports the need for developing tailored prevention strategies based on local characteristics to promote active surveillance programs based on molecular epidemiology.
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  • 文章类型: Journal Article
    毒液是整个动物王国发现的一项非凡的创新,然而,毒液系统在不同群体中的进化起源,包括蜘蛛,仍然神秘。这里,我们调查了普通家蜘蛛的毒液器官的发生,假单胞菌。毒液装置由一对分泌腺组成,每个都通过一条穿过龟头的管道连接到方头的开口。我们进行了大量RNA-seq以鉴定毒腺特异性标志物,并在整个时间序列上使用RNA原位杂交实验测定了它们的表达。这些揭示了腺体原基在胚胎期13在龟头出现,在胚胎发育结束时向近侧进展,并在卵裂后延伸到前瘤。晚期胚胎中重要毒素成分的表达开始标志着毒液分泌细胞的激活。我们选择的标记在成年毒腺中也表现出不同的表达模式:鼠尾草和毒素标记在分泌上皮中表达,叉头和sum-1在周围的肌肉层,而无远端主要在腺体末端表达。我们的研究首次全面分析了蜘蛛的毒腺形态发生,提供有关其演变和发展的关键见解。
    Venom is a remarkable innovation found across the animal kingdom, yet the evolutionary origins of venom systems in various groups, including spiders, remain enigmatic. Here, we investigated the organogenesis of the venom apparatus in the common house spider, Parasteatoda tepidariorum. The venom apparatus consists of a pair of secretory glands, each connected to an opening at the fang tip by a duct that runs through the chelicerae. We performed bulk RNA-seq to identify venom gland-specific markers and assayed their expression using RNA in situ hybridisation experiments on whole-mount time-series. These revealed that the gland primordium emerges during embryonic stage 13 at the chelicera tip, progresses proximally by the end of embryonic development and extends into the prosoma post-eclosion. The initiation of expression of an important toxin component in late postembryos marks the activation of venom-secreting cells. Our selected markers also exhibited distinct expression patterns in adult venom glands: sage and the toxin marker were expressed in the secretory epithelium, forkhead and sum-1 in the surrounding muscle layer, while Distal-less was predominantly expressed at the gland extremities. Our study provides the first comprehensive analysis of venom gland morphogenesis in spiders, offering key insights into their evolution and development.
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  • 文章类型: Journal Article
    一些物种在进化过程中由于各种环境因素而发生了随机突变,导致在系统发育遥远的物种中形成毒液。大多数物种的毒液组成鲜为人知。蛇毒的特征很好,而大多数物种的组成却鲜为人知。相比之下,蛇毒的特征很好,蛋白质和肽是主要的活性和最丰富的成分。已经确定了42个蛋白质家族,包括称为金属蛋白酶的金属蛋白。这些大分子是在其活性位点具有锌的酶,来自解整合素A和金属蛋白酶(ADAM)细胞家族,分为三类(PI,PII和PIII)根据其领域组织。蛇毒金属蛋白酶(SVMP)具有细胞毒性,神经毒性,肌毒性和/或血液毒性在防御和抑制猎物中起关键作用。在这种情况下,envenoming对人类健康构成威胁,被认为是全世界被忽视的疾病,特别是在热带和亚热带国家。然而,“组学”技术的最新进展已经证明了SVMP的有趣生物活性,如抗菌,抗癌,对抗心血管疾病和神经系统疾病。金属蛋白具有转化为药物的治疗潜力,因为毒液的其他成分已经经历了这一过程(例如,卡托普利,tirefiban和eptifibatide)。所以,本章重点介绍有毒物种分泌物中发现的金属蛋白,突出一些方面,如结构,生物活性,药理治疗潜力和。
    Several species during evolution suffered random mutations in response to various environmental factors, which resulted in the formation of venom in phylogenetically distant species. The composition of the venom of most species is poorly known. Snake venom is well characterized while most species have poorly known composition. In contrast, snake venoms are well characterized which proteins and peptides are the main active and most abundant constituents. 42 protein families have been identified, including metalloproteins known as metalloproteinases. These macromolecules are enzymes with zinc in their active site derived from the disintegrin A and metalloproteinase (ADAM) cellular family and are categorized into three classes (PI, PII and PIII) according to their domain organization. The snake venom metalloproteinases (SVMP) are cytotoxic, neurotoxic, myotoxic and/or hematotoxic with a crucial role in the defense and restraint of prey. In this scenario envenoming represents a danger to human health and has been considered a neglected disease worldwide, particularly in tropical and subtropical countries. Nevertheless, recently advances in \"omics\" technologies have demonstrated interesting biological activities of SVMPs such as antimicrobial, anticancer, against cardiovascular diseases and nervous system disorders. Metalloproteins have the therapeutic potential to be converted into drugs as other components of the venom have undergone this process (e.g., captopril, tirefiban and eptifibatide). So, this chapter is focused on the metalloproteins found in the secretions of venomous species, highlight some aspects such as structure, biological activity, pharmacological therapeutic potential and on.
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  • 文章类型: Journal Article
    艰难梭菌感染(CDI)由于高复发率而对健康构成重大威胁。抗微生物药物通常用于治疗CDI相关的腹泻;然而,通过加剧肠道生态失调,抗生素使艰难梭菌孢子萌发和产生毒素,主要毒力因子。因此,使用吸附剂结合外毒素代表了预防和治疗复发的有吸引力的替代药物。在这项研究中,我们提供了天然不溶性多糖的证据,命名为ABR119,由植物细胞培养提取,有效地捕获艰难梭菌毒素。在我们的实验中,ABR119在体外没有表现出细胞毒性并且在体内安全施用。在艰难梭菌相关性结肠炎的动物模型中,ABR119(50mg/kg体重)显着降低结肠髓过氧化物酶活性和炎症的严重程度,防止体重下降。当我们用麦麸多糖处理动物时,这些效果并不明显。我们没有检测到ABR119对艰难梭菌或正常肠道微生物群的细菌物种的细菌杀伤作用。此外,ABR119在体外不干扰大多数临床使用的抗生素的抗微生物活性。总之,ABR119有望通过捕获细菌毒素来治疗和预防艰难梭菌结肠炎,需要进一步的研究来评估ABR119在艰难梭菌引起的人类感染中的潜力。
    Clostridioides difficile infection (CDI) poses a significant health threat due to high recurrence rates. Antimicrobial agents are commonly used to manage CDI-related diarrhoea; however, by aggravating intestinal dysbiosis, antibiotics enable C. difficile spores germination and production of toxins, the main virulence factors. Therefore, the binding of exotoxins using adsorbents represents an attractive alternative medication for the prevention and treatment of relapses. In this study, we provided evidence that the natural insoluble polysaccharides, named ABR119, extracted by plant cell cultures, effectively trap C. difficile toxins. In our experiments, ABR119 exhibited no cytotoxicity in vitro and was safely administered in vivo. In the animal model of C. difficile-associated colitis, ABR119 (50 mg/kg body weight) significantly reduced the colonic myeloperoxidase activity and severity of inflammation, preventing body weight loss. These effects were not evident when we treated animals with wheat bran polysaccharides. We did not detect bacterial killing effects of ABR119 against C. difficile nor against bacterial species of the normal gut microbiota. Moreover, ABR119 did not interfere in vitro with the antimicrobial activities of most clinically used antibiotics. In summary, ABR119 holds promise for treating and preventing C. difficile colitis by trapping the bacterial toxins, warranting further studies to assess the ABR119 potential in human infections caused by C. difficile.
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  • 文章类型: Journal Article
    这是对非织造织物的首次研究,该非织造织物是由尼龙6和用胺(1,4二氨基丁烷二盐酸盐)改性的纳米粘土(Cloisite20A)制成的聚合物纳米复合材料熔喷制成的。形态和物理特征,吸附能力,并提出了抗菌性能。从X射线衍射(XRD)结果,可以观察到信号到其他2θ角的位移,由于α到相移。扫描电子显微镜(SEM)图像显示,纤维的平均直径随着纳米粘土含量的增加而减小。力学测试表明,纯尼龙的撕裂强度为1.734N,但对于含有0.5%改性纳米粘土的样品,这一特性增加到2.135N。尼龙6/C20A1.5%和尼龙6/C20A2%样品在15分钟时的菊粉吸附效率分别为75和74%,分别。尼龙6/C20A1.5%和尼龙6/C20A2%对亚甲基蓝和甲基橙的吸附容量即使在四个吸附循环后仍保持在90%以上。此外,无纺布对大肠杆菌具有抗菌活性。
    This is the first study of non-woven fabrics elaborated by melt-blowing from polymer nanocomposites made of Nylon 6 and nanoclay (Cloisite 20A) modified with an amine (1,4 diaminobutane dihydrochloride). Morphological and physical characteristics, adsorption capacity, and antibacterial properties are presented. From the X-ray diffraction (XRD) results, it was possible to observe a displacement of the signals to other 2θ angles, due to an α to ϒ phase shift. The scanning electron microscopy (SEM) images showed that the mean diameter of fiber decreased as the content of nanoclay increased. The mechanical tests showed that the tear strength force of neat nylon was 1.734 N, but this characteristic increased to 2.135 N for the sample with 0.5% modified nanoclay. The inulin adsorption efficiency of the Nylon 6/C20A 1.5% and Nylon 6/C20A 2% samples at 15 min was 75 and 74%, respectively. The adsorption capacity of Nylon 6/C20A 1.5% and Nylon 6/C20A 2% for methylene blue and methyl orange remained above 90% even after four adsorption cycles. In addition, non-woven fabrics present antibacterial activity against E. coli.
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  • 文章类型: Journal Article
    孕烷X受体(PXR)是一种核激素受体,在调节各种配体的基因表达中起关键作用。特别是外源性物质。在这种情况下,这项研究的目的是阐明在海洋贻贝Mytilusgalloprovincialis中鉴定的四种NR1J1旁系同源物的配体亲和力和功能,采用双荧光素酶报告基因测定。为了实现这一点,这些旁系同源物响应各种毒素的激活模式,包括淡水氰毒素(Anatoxin-a,圆柱精子素,和微囊藻毒素-LR,-RR,和-YR)和海洋藻类毒素(Nodularin,毒素,和河豚毒素),与天然化合物(圣约翰草,熊果酸,和8-甲氧基补骨脂素)和微藻提取物(Tetraselmis,等速疗法,LEGE95046和LEGE11351提取物),被研究过。调查揭示了旁白反应模式的细微差别,突出了MgaNR1J1γ和MgaNR1J1δ旁系同源物对几种毒素的显着敏感性。总之,这项研究揭示了复杂的异源生物代谢和解毒机制,特别关注海洋贻贝NR1J1在响应多种化合物中的作用。此外,与人类PXR的比较分析揭示了解毒机制中潜在的物种特异性适应,暗示进化的含义。这些发现加深了我们对PXR介导的代谢机制的理解,提供对环境监测和进化生物学研究的见解。
    The pregnane X receptor (PXR) is a nuclear hormone receptor that plays a pivotal role in regulating gene expression in response to various ligands, particularly xenobiotics. In this context, the aim of this study was to shed light on the ligand affinity and functions of four NR1J1 paralogs identified in the marine mussel Mytilus galloprovincialis, employing a dual-luciferase reporter assay. To achieve this, the activation patterns of these paralogs in response to various toxins, including freshwater cyanotoxins (Anatoxin-a, Cylindrospermopsin, and Microcystin-LR, -RR, and -YR) and marine algal toxins (Nodularin, Saxitoxin, and Tetrodotoxin), alongside natural compounds (Saint John\'s Wort, Ursolic Acid, and 8-Methoxypsoralene) and microalgal extracts (Tetraselmis, Isochrysis, LEGE 95046, and LEGE 91351 extracts), were studied. The investigation revealed nuanced differences in paralog response patterns, highlighting the remarkable sensitivity of MgaNR1J1γ and MgaNR1J1δ paralogs to several toxins. In conclusion, this study sheds light on the intricate mechanisms of xenobiotic metabolism and detoxification, particularly focusing on the role of marine mussel NR1J1 in responding to a diverse array of compounds. Furthermore, comparative analysis with human PXR revealed potential species-specific adaptations in detoxification mechanisms, suggesting evolutionary implications. These findings deepen our understanding of PXR-mediated metabolism mechanisms, offering insights into environmental monitoring and evolutionary biology research.
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