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Exploring DNA Damage and Repair Mechanisms: A Review with Computational Insights. 探索 DNA 损伤和修复机制:通过计算洞察的综述。
IF 2.7 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-01-16 DOI: 10.3390/biotech13010003
Jiawei Chen, Ravi Potlapalli, Heng Quan, Lingtao Chen, Ying Xie, Seyedamin Pouriyeh, Nazmus Sakib, Lichao Liu, Yixin Xie

DNA damage is a critical factor contributing to genetic alterations, directly affecting human health, including developing diseases such as cancer and age-related disorders. DNA repair mechanisms play a pivotal role in safeguarding genetic integrity and preventing the onset of these ailments. Over the past decade, substantial progress and pivotal discoveries have been achieved in DNA damage and repair. This comprehensive review paper consolidates research efforts, focusing on DNA repair mechanisms, computational research methods, and associated databases. Our work is a valuable resource for scientists and researchers engaged in computational DNA research, offering the latest insights into DNA-related proteins, diseases, and cutting-edge methodologies. The review addresses key questions, including the major types of DNA damage, common DNA repair mechanisms, the availability of reliable databases for DNA damage and associated diseases, and the predominant computational research methods for enzymes involved in DNA damage and repair.

DNA 损伤是导致基因改变的一个关键因素,直接影响人类健康,包括癌症和老年性疾病等疾病的发生。DNA 修复机制在保护基因完整性和预防这些疾病的发生方面发挥着关键作用。过去十年来,DNA 损伤和修复领域取得了重大进展和关键发现。这篇综合综述论文整合了相关研究工作,重点关注 DNA 修复机制、计算研究方法和相关数据库。我们的工作是从事 DNA 计算研究的科学家和研究人员的宝贵资源,提供了对 DNA 相关蛋白质、疾病和前沿方法的最新见解。这篇综述探讨了一些关键问题,包括 DNA 损伤的主要类型、常见的 DNA 修复机制、DNA 损伤和相关疾病的可靠数据库的可用性,以及参与 DNA 损伤和修复的酶的主要计算研究方法。
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引用次数: 0
Styrene Production in Genetically Engineered Escherichia coli in a Two-Phase Culture. 基因工程大肠杆菌在两相培养中生产苯乙烯。
IF 2.7 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-01-14 DOI: 10.3390/biotech13010002
Shuhei Noda, Ryosuke Fujiwara, Yutaro Mori, Mayumi Dainin, Tomokazu Shirai, Akihiko Kondo

Styrene is an important industrial chemical. Although several studies have reported microbial styrene production, the amount of styrene produced in batch cultures can be increased. In this study, styrene was produced using genetically engineered Escherichia coli. First, we evaluated five types of phenylalanine ammonia lyases (PALs) from Arabidopsis thaliana (AtPAL) and Brachypodium distachyon (BdPAL) for their ability to produce trans-cinnamic acid (Cin), a styrene precursor. AtPAL2-expressing E. coli produced approximately 700 mg/L of Cin and we found that BdPALs could convert Cin into styrene. To assess styrene production, we constructed an E. coli strain that co-expressed AtPAL2 and ferulic acid decarboxylase from Saccharomyces cerevisiae. After a biphasic culture with oleyl alcohol, styrene production and yield from glucose were 3.1 g/L and 26.7% (mol/mol), respectively, which, to the best of our knowledge, are the highest values obtained in batch cultivation. Thus, this strain can be applied to the large-scale industrial production of styrene.

苯乙烯是一种重要的工业化学品。虽然已有多项研究报道了微生物苯乙烯的生产,但批量培养产生的苯乙烯量还可以增加。本研究利用基因工程大肠杆菌生产苯乙烯。首先,我们评估了拟南芥(AtPAL)和蕨类植物(BdPAL)中的五种苯丙氨酸氨裂解酶(PALs)生产苯乙烯前体反式肉桂酸(Cin)的能力。表达 AtPAL2 的大肠杆菌能产生约 700 毫克/升的 Cin,而我们发现 BdPALs 能将 Cin 转化为苯乙烯。为了评估苯乙烯的产量,我们构建了一株共同表达 AtPAL2 和来自酿酒酵母的阿魏酸脱羧酶的大肠杆菌。在与油醇进行双相培养后,苯乙烯产量和葡萄糖产量分别为 3.1 克/升和 26.7%(摩尔/摩尔),据我们所知,这是批量培养中获得的最高值。因此,该菌株可用于苯乙烯的大规模工业生产。
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引用次数: 0
Gene Therapy for Genetic Syndromes: Understanding the Current State to Guide Future Care 基因疗法治疗遗传综合征:了解现状,指导未来治疗
Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-01-03 DOI: 10.3390/biotech13010001
Marian L. Henderson, Jacob K. Zieba, Xiaopeng Li, Daniel B. Campbell, Michael R. Williams, Daniel L. Vogt, Caleb P. Bupp, Yvonne Edgerly, S. Rajasekaran, Nicholas L. Hartog, Jeremy Prokop, Jena M. Krueger
Gene therapy holds promise as a life-changing option for individuals with genetic variants that give rise to disease. FDA-approved gene therapies for Spinal Muscular Atrophy (SMA), cerebral adrenoleukodystrophy, β-Thalassemia, hemophilia A/B, retinal dystrophy, and Duchenne Muscular Dystrophy have generated buzz around the ability to change the course of genetic syndromes. However, this excitement risks over-expansion into areas of genetic disease that may not fit the current state of gene therapy. While in situ (targeted to an area) and ex vivo (removal of cells, delivery, and administration of cells) approaches show promise, they have a limited target ability. Broader in vivo gene therapy trials have shown various continued challenges, including immune response, use of immune suppressants correlating to secondary infections, unknown outcomes of overexpression, and challenges in driving tissue-specific corrections. Viral delivery systems can be associated with adverse outcomes such as hepatotoxicity and lethality if uncontrolled. In some cases, these risks are far outweighed by the potentially lethal syndromes for which these systems are being developed. Therefore, it is critical to evaluate the field of genetic diseases to perform cost–benefit analyses for gene therapy. In this work, we present the current state while setting forth tools and resources to guide informed directions to avoid foreseeable issues in gene therapy that could prevent the field from continued success.
基因疗法有望改变基因变异患者的生活。美国食品和药物管理局批准的脊髓性肌肉萎缩症(SMA)、脑腺样白质营养不良症、β-地中海贫血症、A/B 型血友病、视网膜营养不良症和杜氏肌营养不良症的基因疗法已经引起了人们对改变遗传综合征病程的关注。然而,这种兴奋有可能过度扩展到可能不符合基因疗法现状的遗传疾病领域。虽然原位(靶向某一区域)和体外(移除细胞、输送和施用细胞)方法显示了前景,但它们的靶向能力有限。更广泛的体内基因治疗试验显示出各种持续存在的挑战,包括免疫反应、使用与继发性感染相关的免疫抑制剂、过表达的未知结果以及驱动组织特异性校正的挑战。如果不加以控制,病毒递送系统可能会产生不良后果,如肝毒性和致死性。在某些情况下,这些风险远远大于这些系统正在开发的潜在致命综合症。因此,评估遗传疾病领域的基因治疗成本效益分析至关重要。在这项工作中,我们介绍了目前的状况,同时提出了一些工具和资源,以指导人们在知情的情况下避免基因治疗中可预见的问题,这些问题可能会阻碍基因治疗领域继续取得成功。
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引用次数: 0
Biocatalysts Based on Immobilized Lipases for the Production of Fatty Acid Ethyl Esters: Enhancement of Activity through Ionic Additives and Ion Exchange Supports. 基于固定化脂肪酶的生物催化剂用于脂肪酸乙酯的生产:通过离子添加剂和离子交换载体提高活性。
Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2023-12-18 DOI: 10.3390/biotech12040067
Juan S Pardo-Tamayo, Sebastián Arteaga-Collazos, Laura C Domínguez-Hoyos, César A Godoy

Ionic additives affect the structure, activity and stability of lipases, which allow for solving common application challenges, such as preventing the formation of protein aggregates or strengthening enzyme-support binding, preventing their desorption in organic media. This work aimed to design a biocatalyst, based on lipase improved by the addition of ionic additives, applicable in the production of ethyl esters of fatty acids (EE). Industrial enzymes from Thermomyces lanuginosus (TLL), Rhizomucor miehei (RML), Candida antárctica B (CALB) and Lecitase®, immobilized in commercial supports like Lewatit®, Purolite® and Q-Sepharose®, were tested. The best combination was achieved by immobilizing lipase TLL onto Q-Sepharose® as it surpassed, in terms of %EE (70.1%), the commercial biocatalyst Novozyme® 435 (52.7%) and was similar to that of Lipozyme TL IM (71.3%). Hence, the impact of ionic additives like polymers and surfactants on both free and immobilized TLL on Q-Sepharose® was assessed. It was observed that, when immobilized, in the presence of sodium dodecyl sulfate (SDS), the TLL derivative exhibited a significantly higher activity, with a 93-fold increase (1.02 IU), compared to the free enzyme under identical conditions (0.011 IU). In fatty acids ethyl esters synthesis, Q-SDS-TLL novel derivatives achieved results similar to commercial biocatalysts using up to ~82 times less enzyme (1 mg/g). This creates an opportunity to develop biocatalysts with reduced enzyme consumption, a factor often associated with higher production costs. Such advancements would ease their integration into the biodiesel industry, fostering a greener production approach compared to conventional methods.

离子添加剂会影响脂肪酶的结构、活性和稳定性,从而解决常见的应用难题,如防止形成蛋白质聚集或加强酶与支持物的结合,防止它们在有机介质中解吸附。这项工作旨在设计一种基于脂肪酶的生物催化剂,通过添加离子添加剂加以改进,适用于脂肪酸乙酯(EE)的生产。研究人员测试了固定在 Lewatit®、Purolite® 和 Q-Sepharose® 等商业支持物上的来自蓝绿热酵母菌(TLL)、米黑根瘤菌(RML)、白色念珠菌 Antárctica B(CALB)和 Lecitase® 的工业酶。将脂肪酶 TLL 固定在 Q-Sepharose® 上实现了最佳组合,其EE%(70.1%)超过了商用生物催化剂 Novozyme® 435(52.7%),与 Lipozyme TL IM(71.3%)相近。因此,我们评估了聚合物和表面活性剂等离子添加剂对 Q-Sepharose® 上游离和固定 TLL 的影响。结果表明,在十二烷基硫酸钠(SDS)存在的条件下,固定化 TLL 衍生物的活性明显提高,与相同条件下的游离酶(0.011 IU)相比,活性提高了 93 倍(1.02 IU)。在脂肪酸乙酯合成中,Q-SDS-TLL 新型衍生物使用的酶(1 毫克/克)最多减少了约 82 倍,其结果与商业生物催化剂相似。这为开发酶消耗量更低的生物催化剂创造了机会,而酶消耗量的降低往往与生产成本的提高有关。与传统方法相比,这种进步将使生物催化剂更容易融入生物柴油行业,促进更环保的生产方法。
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引用次数: 0
Gibberellin-Producing Bacteria Isolated from Coastal Soil Enhance Seed Germination of Mallow and Broccoli Plants under Saline Conditions. 从沿海土壤中分离出的赤霉素生产细菌可在盐碱条件下提高锦葵和西兰花的种子发芽率。
Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2023-12-11 DOI: 10.3390/biotech12040066
Ji-In Woo, Md Injamum-Ul-Hoque, Nazree Zainurin, Shifa Shaffique, Eun-Hae Kwon, Ho-Jun Gam, Jin Ryeol Jeon, In-Jung Lee, Gil-Jae Joo, Sang-Mo Kang

Salinity hinders plant growth, posing a substantial challenge to sustainable agricultural yield maintenance. The application of plant growth-promoting rhizobacteria (PGPR) offers an emerging strategy to mitigate the detrimental effects of high salinity levels. This study aimed to isolate and identify gibberellin-producing bacteria and their impact on the seed germination of Malva verticillata (mallow) and Brassica oleracea var. italica (broccoli) under salt stress. In this study, seven bacterial isolates (KW01, KW02, KW03, KW04, KW05, KW06, and KW07) were used to assess their capacity for producing various growth-promoting traits and their tolerance to varying amounts of salinity (100 mM and 150 Mm NaCl). The findings revealed that KW05 and KW07 isolates outperformed other isolates in synthesizing indole-3-acetic acid, siderophores, and exopolysaccharides and in solubilizing phosphates. These isolates also enhanced phosphatase activity and antioxidant levels, including superoxide dismutase and catalase. Both KW05 and KW07 isolate highlight the growth-promoting effects of gibberellin by enhancing of growth parameters of Waito-C rice. Further, gas chromatography-mass spectrometry validation confirmed the ability of KW05 and KW07 to produce gibberellins (GAs), including GA1, GA3, GA4, and GA7. Seed germination metrics were enhanced due to the inoculation of KW05 and KW07. Moreover, inoculation with KW05 increased the fresh weight (FW) (7.82%) and total length (38.61%) of mallow under salt stress. Inoculation with KW07 increased the FW (32.04%) and shoot length of mallow under salt stress. A single inoculation of these two isolates increased broccoli plants' FW and shoot length under salt stress. Gibberellin-producing bacteria helps in plant growth promotion by improving salt tolerance by stimulating root elongation and facilitating enhanced absorption of water and nutrient uptake in salty environments. Based on these findings, they can play a role in boosting agricultural yield in salt-affected areas, which would help to ensure the long-term viability of agriculture in coastal regions.

盐分阻碍植物生长,对可持续农业产量的维持构成了巨大挑战。应用促进植物生长的根瘤菌(PGPR)为减轻高盐度的不利影响提供了一种新兴策略。本研究旨在分离和鉴定产生赤霉素的细菌及其对盐胁迫下锦葵和西兰花种子萌发的影响。本研究使用了七种细菌分离物(KW01、KW02、KW03、KW04、KW05、KW06 和 KW07)来评估它们产生各种促进生长性状的能力及其对不同盐度(100 mM 和 150 Mm NaCl)的耐受性。研究结果表明,KW05 和 KW07 分离物在合成吲哚-3-乙酸、苷元、外多糖和溶解磷酸盐方面优于其他分离物。这些分离物还提高了磷酸酶活性和抗氧化剂水平,包括超氧化物歧化酶和过氧化氢酶。KW05 和 KW07 分离物通过提高 Waito-C 水稻的生长参数,突出了赤霉素的生长促进作用。此外,气相色谱-质谱验证证实了 KW05 和 KW07 产生赤霉素(GA)的能力,包括 GA1、GA3、GA4 和 GA7。接种 KW05 和 KW07 后,种子萌发指标得到提高。此外,接种 KW05 还能增加盐胁迫下锦葵的鲜重(7.82%)和总长(38.61%)。接种 KW07 能增加锦葵在盐胁迫下的鲜重(32.04%)和芽长。单一接种这两种分离菌株可增加西兰花植株在盐胁迫下的全长和芽长。产生赤霉素的细菌能刺激根系伸长,促进植物在盐胁迫环境下吸收水分和养分,从而提高耐盐性,有助于促进植物生长。基于这些发现,赤霉素细菌可在提高受盐影响地区的农业产量方面发挥作用,这将有助于确保沿海地区农业的长期生存能力。
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引用次数: 0
Detection and Characterization of Electrogenic Bacteria from Soils 检测土壤中的电生细菌并确定其特征
Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2023-12-02 DOI: 10.3390/biotech12040065
Ana Rumora, Liliana Hopkins, Kayla Yim, Melissa F. Baykus, Luisa Martinez, Luis Jimenez
Soil microbial fuel cells (SMFCs) are bioelectrical devices powered by the oxidation of organic and inorganic compounds due to microbial activity. Seven soils were randomly selected from Bergen Community College or areas nearby, located in the state of New Jersey, USA, were used to screen for the presence of electrogenic bacteria. SMFCs were incubated at 35–37 °C. Electricity generation and electrogenic bacteria were determined using an application developed for cellular phones. Of the seven samples, five generated electricity and enriched electrogenic bacteria. Average electrical output for the seven SMFCs was 155 microwatts with the start-up time ranging from 1 to 11 days. The highest output and electrogenic bacterial numbers were found with SMFC-B1 with 143 microwatts and 2.99 × 109 electrogenic bacteria after 15 days. Optimal electrical output and electrogenic bacterial numbers ranged from 1 to 21 days. Microbial DNA was extracted from the top and bottom of the anode of SMFC-B1 using the ZR Soil Microbe DNA MiniPrep Protocol followed by PCR amplification of 16S rRNA V3-V4 region. Next-generation sequencing of 16S rRNA genes generated an average of 58 k sequences. BLAST analysis of the anode bacterial community in SMFC-B1 demonstrated that the predominant bacterial phylum was Bacillota of the class Clostridia (50%). However, bacteria belonging to the phylum Pseudomonadota (15%) such as Magnetospirillum sp. and Methylocaldum gracile were also part of the predominant electrogenic bacterial community in the anode. Unidentified uncultured bacteria accounted for 35% of the predominant bacterial community. Bioelectrical devices such as MFCs provide sustainable and clean alternatives to future applications for electricity generation, waste treatment, and biosensors.
土壤微生物燃料电池(smfc)是一种生物电装置,由微生物活性引起的有机和无机化合物氧化提供动力。从美国新泽西州卑尔根社区学院或附近地区随机抽取7份土壤,用于筛选电致细菌的存在。smfc在35-37℃孵育。利用为手机开发的应用程序来测定发电和致电细菌。在7个样品中,有5个产生了电并富集了致电细菌。7个smfc的平均电输出为155微瓦,启动时间从1到11天不等。SMFC-B1在143微瓦时产电细菌最多,15 d后产电细菌数为2.99 × 109个。最佳电输出和电致细菌数量为1 ~ 21天。采用ZR土壤微生物DNA MiniPrep协议从SMFC-B1阳极的顶部和底部提取微生物DNA,并对16S rRNA V3-V4区进行PCR扩增。16S rRNA基因的下一代测序平均产生58 k序列。对SMFC-B1阳极菌群的BLAST分析表明,优势菌门为梭状芽孢杆菌门(50%)。然而,假单胞菌门的细菌(15%),如磁螺旋藻和甲藻也是阳极上主要的电生细菌群落的一部分。未鉴定的未培养细菌占优势菌群的35%。诸如mfc之类的生物电设备为未来的发电、废物处理和生物传感器的应用提供了可持续和清洁的替代品。
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引用次数: 0
Fungicide Resistance in Botrytis spp. and Regional Strategies for Its Management in Northern European Strawberry Production. 北欧草莓中葡萄孢菌的抗杀菌剂抗性及区域管理策略。
Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2023-11-19 DOI: 10.3390/biotech12040064
Roland W S Weber, Antonios Petridis

Grey mould, caused by Botrytis cinerea and other Botrytis spp., is a major cause of fruit rot in strawberries and other fruit crops worldwide. Repeated fungicide applications are essential in order to secure harvests. However, resistance to all currently registered single-site fungicides is widespread. The rising importance of strains with multiple resistance to most or all fungicides is of particular concern. These strains may be introduced into fields via contaminated nursery plants and/or by immigration from adjacent plots. On the basis of research conducted in northern German and Danish strawberry production, a concept to manage fungicide resistance under northern European conditions has been developed and put into regional strawberry production practice. This principally includes the testing of nursery plants for fungicide-resistant Botrytis strains prior to planting; the restricted and specific use of fungicides at flowering in the production fields, taking account of the resistance spectrum within the local Botrytis population; and crop sanitation measures such as the removal of rotting fruits at the beginning of harvest. Further options such as protected cultivation, reduced fertilisation and biological control are also discussed. The practical implementation of such a strategy in northern Germany and Denmark has been shown to reduce the occurrence of multi-resistant strains to a tolerable steady-state level.

灰霉是由灰霉菌和其他灰霉菌引起的,是全世界草莓和其他水果作物腐烂的主要原因。为了确保收成,反复使用杀菌剂是必不可少的。然而,对所有目前登记的单位点杀菌剂的耐药性是普遍存在的。对大多数或所有杀菌剂具有多重抗性的菌株日益重要,这是特别值得关注的。这些菌株可能通过受污染的苗圃和/或从邻近地块移民引入田间。在对德国北部和丹麦草莓生产进行研究的基础上,提出了在北欧条件下管理杀菌剂抗性的概念,并将其应用于区域草莓生产实践。这主要包括在种植前对苗圃进行抗杀菌剂葡萄孢菌株的测试;考虑到当地葡萄孢菌群的抗性谱,限制和特定使用杀菌剂;农作物卫生措施,如在收获之初清除腐烂的水果。进一步的选择,如保护栽培、减少施肥和生物防治也进行了讨论。这种战略在德国北部和丹麦的实际实施已被证明可将多重耐药菌株的发生减少到可容忍的稳态水平。
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引用次数: 0
The Controversial Nature of Some Non-Starter Lactic Acid Bacteria Actively Participating in Cheese Ripening 一些非发酵剂乳酸菌积极参与奶酪成熟的争议性
Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2023-11-09 DOI: 10.3390/biotech12040063
Svetoslav G. Dimov
This mini review deals with some controversial non-starter lactic acid bacteria (NSLAB) species known to be both human and animal pathogens but also health-promoting and probiotic. The focus is on Lactococcus garvieae, two Streptococcus species (S. uberis and S. parauberis), four Weissella species (W. hellenica, W. confusa, W. paramesenteroides, and W. cibaria), and Mammalicoccus sciuri, which worldwide, are often found within the microbiotas of different kinds of cheese, mainly traditional artisanal cheeses made from raw milk and/or relying on environmental bacteria for their ripening. Based on literature data, the virulence and health-promoting effects of these bacteria are examined, and some of the mechanisms of these actions are reviewed. Additionally, their possible roles in cheese ripening are also discussed. The analysis of the literature data available so far showed that, in general, the pathogenic and the beneficial strains, despite belonging to the same species, show somewhat different genetic constitutions. Yet, when the safety of a given strain is assessed, genomic analysis on its own is not enough, and a polyphasic approach including additional physiological and functional tests is needed.
这篇小型综述涉及一些有争议的非起始乳酸菌(NSLAB)物种,已知它们既是人类和动物的病原体,也是促进健康和益生菌。重点是garvieae乳球菌、两种链球菌(uberis链球菌和副auberis链球菌)、四种Weissella链球菌(W. hellenica、W. confusa、W. paresenteroides和W. cibaria)和sciuri哺乳球菌,它们通常存在于世界各地不同种类奶酪的微生物群中,主要是由生牛奶制成的传统手工奶酪和/或依赖环境细菌成熟的奶酪。在文献资料的基础上,研究了这些细菌的毒力和促进健康的作用,并对这些作用的一些机制进行了综述。此外,还讨论了它们在奶酪成熟过程中的可能作用。对现有文献资料的分析表明,一般情况下,致病菌株和有益菌株虽然属于同一种,但遗传结构有所不同。然而,在评估特定菌株的安全性时,仅靠基因组分析是不够的,还需要包括额外生理和功能测试在内的多相方法。
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引用次数: 0
Tracking of Systemic Lupus Erythematosus (SLE) Longitudinally Using Biosensor and Patient-Reported Data: A Report on the Fully Decentralized Mobile Study to Measure and Predict Lupus Disease Activity Using Digital Signals—The OASIS Study 利用生物传感器和患者报告的数据纵向跟踪系统性红斑狼疮(SLE):利用数字信号测量和预测狼疮疾病活动的完全分散移动研究报告- OASIS研究
Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2023-11-09 DOI: 10.3390/biotech12040062
Eldon R. Jupe, Gerald H. Lushington, Mohan Purushothaman, Fabricio Pautasso, Georg Armstrong, Arif Sorathia, Jessica Crawley, Vijay R. Nadipelli, Bernard Rubin, Ryan Newhardt, Melissa E. Munroe, Brett Adelman
(1) Objective: Systemic lupus erythematosus (SLE) is a complex disease involving immune dysregulation, episodic flares, and poor quality of life (QOL). For a decentralized digital study of SLE patients, machine learning was used to assess patient-reported outcomes (PROs), QOL, and biometric data for predicting possible disease flares. (2) Methods: Participants were recruited from the LupusCorner online community. Adults self-reporting an SLE diagnosis were consented and given a mobile application to record patient profile (PP), PRO, and QOL metrics, and enlisted participants received smartwatches for digital biometric monitoring. The resulting data were profiled using feature selection and classification algorithms. (3) Results: 550 participants completed digital surveys, 144 (26%) agreed to wear smartwatches, and medical records (MRs) were obtained for 68. Mining of PP, PRO, QOL, and biometric data yielded a 26-feature model for classifying participants according to MR-identified disease flare risk. ROC curves significantly distinguished true from false positives (ten-fold cross-validation: p < 0.00023; five-fold: p < 0.00022). A 25-feature Bayesian model enabled time-variant prediction of participant-reported possible flares (P(true) > 0.85, p < 0.001; P(nonflare) > 0.83, p < 0.0001). (4) Conclusions: Regular profiling of patient well-being and biometric activity may support proactive screening for circumstances warranting clinical assessment.
(1)目的:系统性红斑狼疮(SLE)是一种复杂的疾病,涉及免疫失调、发作性发作和生活质量差。对于SLE患者的分散数字研究,使用机器学习来评估患者报告的结果(PROs)、生活质量(QOL)和生物特征数据,以预测可能的疾病爆发。(2)方法:参与者从LupusCorner网络社区中招募。自我报告SLE诊断的成年人同意并给予移动应用程序来记录患者概况(PP), PRO和QOL指标,并且入选的参与者接受智能手表进行数字生物识别监测。使用特征选择和分类算法对所得数据进行分析。(3)结果:550名参与者完成了数字调查,144人(26%)同意佩戴智能手表,68人获得了医疗记录(MRs)。对PP、PRO、QOL和生物特征数据的挖掘产生了一个26个特征的模型,用于根据mr识别的疾病爆发风险对参与者进行分类。ROC曲线显著区分真阳性和假阳性(十倍交叉验证:p <0.00023;五重:p <0.00022)。一个25个特征的贝叶斯模型能够对参与者报告的可能的耀斑进行时变预测(P(true) >0.85, p <0.001;P (nonflare)比;0.83, p <0.0001)。(4)结论:定期分析患者的健康状况和生物特征活动可能有助于主动筛查需要临床评估的情况。
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引用次数: 0
Bacterial Proteases as Potentially Exploitable Modulators of SARS-CoV-2 Infection: Logic from the Literature, Informatics, and Inspiration from the Dog 细菌蛋白酶作为SARS-CoV-2感染的潜在可利用调节剂:文献逻辑、信息学和狗的启示
Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2023-10-30 DOI: 10.3390/biotech12040061
Gerald H. Lushington, Annika Linde, Tonatiuh Melgarejo
(1) Background: The COVID-19 pandemic left many intriguing mysteries. Retrospective vulnerability trends tie as strongly to odd demographics as to exposure profiles, genetics, health, or prior medical history. This article documents the importance of nasal microbiome profiles in distinguishing infection rate trends among differentially affected subgroups. (2) Hypothesis: From a detailed literature survey, microbiome profiling experiments, bioinformatics, and molecular simulations, we propose that specific commensal bacterial species in the Pseudomonadales genus confer protection against SARS-CoV-2 infections by expressing proteases that may interfere with the proteolytic priming of the Spike protein. (3) Evidence: Various reports have found elevated Moraxella fractions in the nasal microbiomes of subpopulations with higher resistance to COVID-19 (e.g., adolescents, COVID-19-resistant children, people with strong dietary diversity, and omnivorous canines) and less abundant ones in vulnerable subsets (the elderly, people with narrower diets, carnivorous cats and foxes), along with bioinformatic evidence that Moraxella bacteria express proteases with notable homology to human TMPRSS2. Simulations suggest that these proteases may proteolyze the SARS-CoV-2 spike protein in a manner that interferes with TMPRSS2 priming.
(1)背景:新冠肺炎大流行留下了许多耐人寻味的谜团。回顾性脆弱性趋势与奇怪的人口统计数据、暴露概况、遗传、健康或既往病史密切相关。这篇文章记录了鼻微生物组特征在区分不同感染亚群的感染率趋势中的重要性。(2)假设:通过详细的文献调查、微生物组分析实验、生物信息学和分子模拟,我们提出假单胞菌属中特定的共生细菌物种通过表达可能干扰Spike蛋白水解启动的蛋白酶来抵抗SARS-CoV-2感染。(3)证据:各种报告发现,在对COVID-19具有较高抗性的亚群(如青少年、对COVID-19具有抗性的儿童、饮食多样性强的人群和杂食性犬)中,莫拉菌的鼻腔微生物组含量较高,而在易感亚群(如老年人、饮食狭窄的人群、食肉猫和狐狸)中含量较低,同时生物信息学证据表明,莫拉菌表达的蛋白酶与人类TMPRSS2具有显著的同源性。模拟表明,这些蛋白酶可能以干扰TMPRSS2启动的方式水解SARS-CoV-2刺突蛋白。
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引用次数: 0
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BioTech
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