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JOURNAL OF BIOMATERIALS APPLICATIONS · 2024 · IF 2.3

Reactive oxygen species-responsive nano gel as a carrier, combined with photothermal therapy and photodynamic therapy for the treatment of brucellosis

Yuchang Qin,Yuanyuan Xu,Fuli Lin,Yinwei Qiu,Yujie Luo,Xuan Lv,Tianyu Liu,Yongsheng Li,Zhiyong Liu,Shengchao Yang

Brucellosis is an intracellular infectious disease that is primarily treated with antibacterial therapy. However, most antibacterial drugs struggle to penetrate the cell membrane and may be excluded or inactivated within the cell. In a recent study, researchers developed a nanogel coated with polydopamine (PDA) that responds to reactive oxygen species (ROS) and has enhanced adhesion properties. This nanogel encapsulates photosensitized zinc phthalocyanine (ZnPc) and an antibacterial drug, and is further modified with folic acid (FA) for active targeting. The resulting ROS-responsive nanogel, termed PDA@PMAA@ZnPc@DH-FA, can reach temperatures up to 50°C under near-infrared light, leading to a 72.1% improvement in drug release through increased ROS production. Cell staining confirmed a cell survival rate above 75%, with a low hemolysis rate of only 4.633%, indicating excellent biocompatibility. Furthermore, the study’s results showed that the nanogel exhibited stronger killing effects against Brucella compared to administering the drug alone. Under near-infrared irradiation, the nanogel achieved a bacteriostatic rate of 99.8%. The combined approach of photothermal therapy and photodynamic therapy offers valuable insights for treating Brucella.

研究领域: 医学 · 生物材料学 · 感染病学
✓ 已验证 DOI PubMed 高影响因子
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Journal of Materials Chemistry B · 2024 · IF 6.1

Combined and rapid detection of anti-Brucella IgG/IgM in clinical samples based on surface-enhanced Raman scattering-lateral flow immunochromatography

Yongwei Zhang,Ziyue Li,Aolin Zhu,Qian Zhang,Hao Zhou,Xuelei Zhou,Tingwei Liu,Chunyan Liu,Hefei Zha,Xin Zhang,Hui Zhao,Jiutong Li,Guodong Lü,Xinxia Li

Brucellosis is a bacterial infectious disease caused mainly by Brucella. Transmission is mainly by contact with infected domestic or wild animals or their excreta. Clinical diagnosis of brucellosis is usually based on qualitative total antibody tests, which make it difficult to differentiate between acute and pre-existing infections. In this study, for the simultaneous detection of anti-brucellosis IgG and IgM, we innovatively developed a surface-enhanced Raman scattering (SERS)-lateral flow immunoassay (LFIA) detection system, and evaluated its performance and diagnostic effect by using clinical serum samples. The key design of this biosensor involves the preparation of two immunoprobes using two Raman spheres (R-Sphere) with distinct signals conjugated to mouse anti-human IgG and IgM, respectively. In this design, brucellosis-specific antigens are embedded in the T-line, allowing simultaneous capture of anti-brucellosis IgG and IgM in a specific binding reaction. A portable Raman instrument is used to detect the characteristic signal intensities generated by IgM and IgG on the T-line, which can then be used to analyze the target IgM and IgG antibodies. Based on the analysis of 40 clinical samples, the method has a sensitivity and specificity of 100%, and the detection time is only 15 min. The advantages of this technology are fast speed, convenient use, high sensitivity, and it can distinguish the disease course to achieve precise treatment. These features make it an ideal solution for large-scale brucellosis testing in remote and nomadic areas, where it can play a crucial role in improving public health protection.

CAS / MDL: 60-00-4
研究领域: 医学诊断 · 生物传感技术 · 传染病研究
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Frontiers in Cellular and Infection Microbiology · 2025 · IF 4.8

Preparation and evaluation of Brucella T4SS recombinant proteins in serodiagnosis of human brucellosis based on TMT-based proteomics technology

Qi Wu,Chen Sun,Liping Guo,Yujia Xie,Jinpeng Zhang,Dehui Yin

Introduction: Brucellosis, a significant zoonotic infectious disease, poses a global health threat. Accurate and efficient diagnosis is crucial for prevention, control, and treatment of brucellosis. VirB proteins, components of the Type IV secretion system (T4SS) in Brucella, play a pivotal role in bacterial virulence and pathogenesis but have been understudied for their diagnostic potential.Methods: Tandem Mass Tag (TMT) proteomics technology was utilized to identify highly expressed VirB proteins from wild-type Brucella strains. Recombinant T4SS proteins were prepared, and an indirect ELISA method was established for serological diagnosis of human brucellosis.Results: Seven T4SS proteins (rVirB3, rVirB4, rVirB9, rBMEII0036, rVirB8, rVirB11, and rVirB10) were expressed used to construct the indirect ELISA method which showed high diagnostic accuracy. Sensitivity and specificity of the proteins exceeded 0.9100 and 0.9167, respectively, demonstrating good performance comparable to traditional LPS and Rose Bengal Ag antigens. Cross-reactivity was observed in a limited number of serum samples from febrile patients without brucellosis.Conclusions: The study highlights the potential of VirB proteins as novel diagnostic antigens for human brucellosis. Future research can further optimize the use of VirB proteins in diagnostic assays and explore their applications in vaccine development.

研究领域: 传染病学 · 蛋白质组学 · 医学诊断
✓ 已验证 DOI PubMed 高影响因子
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Journal of Food Measurement and Characterization · 2022 ·Vol. 16 ·期 5 ·3501-3511 · IF 3.006

Highly sensitive detection of Brucella in milk by cysteamine functionalized nanogold/4-Mercaptobenzoic acid electrochemical biosensor

Chen Hongshuo,Liu Haibin,Cui Chuanjin,Zhang Xuechao,Yang Wei,Zuo Yueming

To effectively cut off the transmission of Brucella to humans through milk, a novel biosensor for detection of Brucella was constructed using cysteamine functionalized nanogold (Cys-Au) and 4-Mercaptobenzoic acid (4-MBA) modified gold electrode as the platform. The morphology of the prepared nanomaterials was characterized by laser particle sizer, XPS and SEM, and the results showed the 4-MBA film was modified on the gold electrode surface, and the diameter of successfully prepared nanogold and Cys-Au are about 55 and 65 nm, respectively. The electrochemical performance of the biosensor was tested in Brucella antigen solution by square wave voltammetry (SWV). The results showed the reproducibility and stability of the biosensor were good, the spiked recovery in milk was in the range of 95.12–105.27%, and the minimum detection limit (S/N = 3) was 5.12 × 10 2  cfu/mL with a linear range from 1.6 × 10 2 to 1.6 × 10 8  cfu/mL. In addition, the minimum detection limit was reduced from 5.12 × 10 2  cfu/mL to 7.0 × 10 1  cfu/mL after processing the SWV data by second-order derivative transformation, which showed Second-order derivative transformation is very helpful to further optimize the performance of the sensor. Compared with the previously reported test methods, the prepared biosensors have a wider linear range and lower limit of detection (LOD). Therefore, the constructed biosensor can be used as a promising tool for the trace detection of Brucella in milk samples.

研究领域: 食品科学 · 微生物学 · 生物传感技术
✓ 已验证 DOI 高影响因子
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JOURNAL OF FOOD SCIENCE AND TECHNOLOGY-MYSORE · 2022 ·Vol. 59 ·期 12 ·4653-4662 · IF 3.117

Recombinant protein G/Au nanoparticles/graphene oxide modified electrodes used as an electrochemical biosensor for Brucella Testing in milk

Chen Hongshuo,Liu Haibin,Cui Chuanjin,Zhang Wensi,Zuo Yueming

In this study, a simple label-free biosensor for Brucella was constructed, which based on the screen-printed carbon electrode (SPCE) modified by Recombinant protein G/gold nanoparticles/graphene oxide (RpG/Au/GO). The impedance responses of the proposed biosensor were measured by electrochemical AC impedance method in Brucella antigen gradient concentration solutions. The results showed that the linear range of this biosensor was from 1.6 × 10 2  CFU/mL to 1.6 × 10 8  CFU/mL with the minimum detection limit of 3.2 × 10 2  CFU/mL (S/N = 3). Moreover, the biosensor for Brucella detection possessed acceptable reproducibility with a relative standard deviation of 5.15% and acceptable stability with a relative standard deviation of 4.68%. The spiked recovery rate in actual pasteurized milk samples was more than 92% . Therefore, the developed biosensor exhibits excellent prospects in the selective quantification detection of Brucella abortus .

研究领域: 生物传感技术 · 食品检测 · 微生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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SENSORS AND ACTUATORS B-CHEMICAL · 2025 · IF 7.7

Construction of dual-signal electrochemical sensors based on the coordination chemical reaction of Fe2+ and K3[Fe(CN)6] for detecting Brucella vaccine and wild strains

Xiaotong Wang,Tongtong Ye,Shaohui Geng,Shuna Ren,Xuming Zhao,Lihua Chen

A dual-signal strategy was developed based on a coordination reaction between iron(II) ions (Fe 2+ ) and potassium hexacyanoferrate(III) (K 3 [Fe(CN) 6 ]) to distinguish between brucella vaccine and wild strain. Utilizing metal-organic frameworks (MOFs), MOF Al (aluminum) @Fe 2+ @P 1 and MOF Fe @P 2 were synthesized and affixed to a hyaluronic acid (HA)-doped electrode. Hairpin probe 1 (P 1 ) has a common sequence (P 1 ') recognizing a fragment (T 1 ) in vaccines and wild strains. In contrast, hairpin probe 2 (P 2 ) has a differential sequence (P 2 ') only targeting a specific fragment (T 2 ) in the wild strain. Experimental findings indicated that activation of T 1 led to the dissociation of P 1 from MOF Al @Fe 2+ @P 1 , which released Fe 2+ into a buffer containing trace Fe 2+ . Following this, the addition of hydrogen peroxide (H 2 O 2 ) and K 3 [Fe(CN) 6 ] resulted in the formation of KFe[Fe(CN) 6 ] (PB). In contrast, specific activation of T 2 caused the detachment of P 2 from MOF Fe , thereby exposing its catalytic site. In H 2 O 2 , this catalytic site facilitated the conversion of trace Fe 2+ in buffer to Fe 3+ , with no PB generated after the addition of K 3 [Fe(CN) 6 ]. Simultaneous activation of T 1 and T 2 promoted the oxidation of Fe 2+ released from MOF Al by the exposed catalytic site of MOF Fe . The ratio of K 3 [Fe(CN) 6 ] to PB exhibited dynamic changes. Specifically, the ratio below 2.37 ± 0.05 indicated a Brucella-positive sample, whereas a ratio under 0.9 ± 0.02 suggested a sample derived from the vaccine. The scarcity of dual-signal sensors employing coordination reactions underscores the significance of this approach. Moreover, it addressed the challenges associated with brucella detection, demonstrating robust analytical performance.

研究领域: 生物化学 · 医学检测 · 分析化学
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SENSORS AND ACTUATORS B-CHEMICAL · 2024 · IF 8

Fluorescent dual-signal immunosensor combined with machine learning algorithm for accuracy discrimination of natural Brucella infection and vaccination

Deying Zou,Jiang Chang,Shiying Lu,Pan Hu,Kai Zhang,Cheng Han,Feng Li,Yansong Li,Dan Chi,Mengyan Cheng,Jianfeng Xu,Xiaoli Sun,Zengshan Liu,Honglin Ren

Brucellosis is a worldwide zoonoses posing a significant threat to humans and animals. The difficulty in distinguishing between Brucella infection and vaccination has led to substantial health risks and economic losses. In this study, we developed a fluorescent dual-signal immunosensor, integrating it with machine learning to solve this problem. Immunogens were selected through structural analysis, followed by the screening of monoclonal antibodies. The antibodies were conjugated with fluorescent microspheres, serving as immunoprobes. Employing a dual-antibody sandwich strategy, we prepared the immunosensor and utilized machine learning to analyze the correlation between multibiomarkers and the status of Brucella infection or vaccine-induced immunity. The immunosensor achieved detection limits of 7.56 pg/mL for IL-1β and 76.61 pg/mL for IL-1Ra, without cross-reactivity with common inflammatory factors. Utilizing the Random Forest algorithm, the combination of the IL-1Ra/IL-1β ratio and RBPT achieved a F1 score of 1.0. Overall, the strategy effectively distinguishes between Brucella -infected and vaccinated subjects, offering valuable applications for brucellosis monitoring.

CAS / MDL: 1185-53-1
研究领域: 医学诊断 · 免疫学 · 生物信息学
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES · 2023 ·Vol. 24 ·期 13 ·10744 · IF 5.6

Alr Gene in Brucella suis S2: Its Role in Lipopolysaccharide Biosynthesis and Bacterial Virulence in RAW264.7

Mingyue Hao,Minghui Wang,Danyu Zhao,Yong Shi,Ye Yuan,Junmei Li,Yunyi Zhai,Xiaofang Liu,Dong Zhou,Huatao Chen,Pengfei Lin,Keqiong Tang,Wei Liu,Yaping Jin,Aihua Wang

Brucella suis, the causative agent of brucellosis, poses a significant public health and animal husbandry threat. However, the role of the alanine racemase (alr) gene, which encodes alanine racemase inBrucella, remains unclear. Here, we analyzed analrdeletion mutant and a complemented strain ofBrucella suisS2. The knockout strain displayed an unaltered, smooth phenotype in acriflavine agglutination tests but lacked the core polysaccharide portion of lipopolysaccharide (LPS). Genes involved in the LPS synthesis were significantly upregulated in the deletion mutant. Thealrdeletion strain exhibited reduced intracellular viability in the macrophages, increased macrophage-mediated killing, and upregulation of the apoptosis markers. Bcl2, an anti-apoptotic protein, was downregulated, while the pro-apoptotic proteins, Bax, Caspase-9, and Caspase-3, were upregulated in the macrophages infected with the deletion strain. The infected macrophages showed increased mitochondrial membrane permeability, Cytochrome C release, and reactive oxygen species, activating the mitochondrial apoptosis pathway. These findings revealed that alanine racemase was dispensable inB. suisS2 but influenced the strain’s rough features and triggered the mitochondrial apoptosis pathway during macrophage invasion. The deletion of thealrgene reduced the intracellular survival and virulence. This study enhances our understanding of the molecular mechanism underlyingBrucella’s survival and virulence and, specifically, howalrgene affects host immune evasion by regulating bacterial LPS biosynthesis.Keywords:Brucella suisS2;alanine racemase;alr;lipopolysaccharide;apoptosis;mitochondrial membrane potential;intracellular survival

CAS / MDL: 8048-52-0
研究领域: 微生物学 · 分子生物学 · 传染病学 · 免疫学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Scientific Reports · 2025 ·Vol. 15 ·期 1 ·1-7 · IF 3.9

Application of Brucella type IV secretion proteins VirB1, VirB5, and VirB6 in the serological diagnosis of brucellosis

Wang Lei,Zhao Shiqi,Qi Xinru,Pei Qichuan,Chen Yixiao,Yin Dehui,Yao Meixue

Brucellosis, a significant zoonotic infectious disease caused by Brucella spp. , necessitates the development of efficient, rapid, accurate, and cost-effective diagnostic methods. This study evaluated the diagnostic value of Brucella Type IV secretion proteins VirB1, VirB5, and VirB6 for human brucellosis serological diagnosis. A total of 100 positive serum samples, 96 negative serum samples, and 27 serum samples from patients with fever caused by other pathogens were collected. Recombination VirB1 (rVirB1), rVirB5, and rVirB6 were expressed using prokaryotic expression systems, while VirB2 and VirB7 were synthesized as peptides. An indirect ELISA method was established using purified proteins and synthetic peptides, with sensitivity, specificity, AUC, and cut-off values determined through ROC analysis. The study successfully prepared rVirB1 (~ 36 kD, purity 90.6%), rVirB5 (~ 32 kD, purity 90.3%), and rVirB6 (~ 28 kD, purity 94.9%). These proteins exhibited sensitivity and specificity exceeding 0.9500 and 0.9271, respectively, comparable to traditional LPS antigens. Cross-reactivity assessments revealed that rVirB1 exhibited cross-reactivity with Pseudomonas putrida , while rVirB5 and rVirB6 showed no cross-reactivity. In contrast, LPS exhibited 14 instances of cross-reactivity. This study successfully developed an indirect ELISA diagnostic method using rVirB1, rVirB5, and rVirB6, demonstrating high diagnostic accuracy comparable to traditional LPS antigen detection techniques. Although some cross-reactivity was observed, the method presents a promising new candidate for the serological diagnosis of brucellosis. Future research should focus on optimizing this method to enhance diagnostic specificity and reliability.

研究领域: 传染病学 · 微生物学 · 免疫学 · 分子诊断学
✓ 已验证 DOI PubMed 高影响因子
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CHIRALITY · 2024 ·Vol. 36 ·期 2 ·e23643 · IF 2.8

Resolution of N-acetyl-DL-methionine methyl ester by the lipase from Brucella thiophenivorans

Xiaojun Li,Qi Li,Liying Yang,Liqin Huang,Chenchen Peng,Jianyong Zheng

In this study, lipase-catalyzed resolution of N-acetyl-DL-methionine methyl ester (N-Ac-DL-MetOMe) was evaluated. A lipase from Brucella thiophenivorans was prone to exhibit high activity and excellent enantioselectivity toward N-Ac-DL-MetOMe to produce the key chiral intermediate N-acetyl-L-methionine methyl ester (N-Ac-L-MetOMe). The results showed that the enzymatic reaction was carried out in 100 g/L racemic substrate for 2 h, the conversion reached 51.3%, the enantiomeric excess value N-Ac-L-MetOMe exceeded 99%, and the enantiomeric ratio value >200. Therefore, the lipase from B. thiophenivorans has potential prospects for the resolution of N-Ac-DL-MetOMe to produce the important intermediate N-Ac-L-MetOMe.

研究领域: 生物催化 · 酶工程 · 有机化学
✓ 已验证 DOI PubMed 高影响因子
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Coatings · 2021 ·Vol. 11 ·期 2 ·147 · IF 2.881

An Active Gelatin Coating Containing Eugenol and Vacuum Delays the Decay of Chinese Seabass (Lateolabrax maculatus) Fillets during Cold Storage: A Microbiome Perspective

Xuan Ma,Qianqian Zhou,Weiqiang Qiu,Jun Mei,Jing Xie

The purpose of this study was to evaluate the effect of an active gelatin coating containing eugenol and vacuum on the microbial diversity of Chinese seabass (Lateolabrax maculatus) during cold (−0.9 °C) storage. The bacterial sequences in Chinese seabass were observed using a high-throughput sequencing technique targeting the V3–V4 region of the 16S Ribosomal DNA (rDNA) on 0, 12th, and 24th day, which showed a more comprehensive estimate of the microbial diversity in seabass samples compared with microbial enumeration. The results revealed that the species diversity of fresh seabass was rich, mainly includingCarnobacterium,Glutamicibacter, andPseudomonas, with abundance ratios of 0.286, 0.160, and 0.130, respectively.PseudomonasandShewanellawere the primary contaminants in the spoiled control samples, where the abundance ratios increased from 0.220 and 0.174 on the 12th day to 0.802 and 0.163 on the 24th day, respectively. Vacuum treatment could inhibit the growth ofPseudomonasandShewanellasuch that when stored on the 12th day,Brochothrixbecame the superior genus. However,PseudomonasandShewanelladominated the storage until the 24th day, where their abundance ratios were 0.343 and 0.279, respectively. The inhibition ofPseudomonasandCarnobacteriumwas gradually enhanced with increasing concentrations of eugenol. Furthermore, an active gelatin coating containing eugenol and vacuum treatment was more effective at inhibiting the increase of the total volatile basic nitrogen. This study confirmed that an active gelatin coating containing eugenol and vacuum could reduce the species of bacteria, inhibit the growth and reproduction of the main dominant spoilage bacteria, and delay the spoilage of seabass.Keywords:coating preservation;high-throughput sequencing;shelf life;diversity

CAS / MDL: 97-53-0
研究领域: 食品科学 · 微生物学 · 生物技术
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Bioengineered · 2022 · IF 6.832

Identification of cerebrospinal fluid metabolites as biomarkers for neurobrucellosis by liquid chromatography-mass spectrometry approach

Hao Yang,Zhenfei Wang,Shujun Shi,Qin Yu,Meiling Liu,Zhelin Zhang

Neurobrucellosis is the most morbid form in brucellosis disease. Metabolomics is an emerging method which intends to explore the global alterations of various metabolites in samples. We aimed to identify metabolites in cerebrospinal fluid (CSF) as biomarkers that were potentially unique for neurobrucellosis. CSF samples from 25 neurobrucellosis patients and 25 normal controls (uninfected patients with hydrocephalus) were collected for metabolite detection using liquid chromatography-mass spectrometry (LC-MS) approach. Inflammatory cytokines in CSF were measured with Enzyme-linked immunosorbent assay (ELISA). The base peak chromatogram in CSF samples showed that small-molecule metabolites were well separated. Principal Component Analysis (PCA) analysis exhibited the examined samples were arranged in two main clusters in accordance with their group. Projection to Latent Structures Discriminant Analysis (PLS-DA) revealed there was a noticeable separation between neurobrucellosis and normal groups. Orthogonal Partial Least-Squares-Discriminant Analysis (OPLS-DA) could responsibly illuminate the differences between neurobrucellosis and normal controls. Neurobrucellosis showed a total of 155 differentiated metabolites. Prominent potential biomarkers including 30 metabolites were then selected out, regarded as more capable of distinguishing neurobrucellosis. TNF-α and IL-6 in CSF were remarkably increased in neurobrucellosis. We presented the heatmaps and correlation analyses among the identified 30 potential biomarkers. In conclusion, this study showed that CSF metabolomics based on LC-MS could distinguish neurobrucellosis patients from normal controls. Our data offered perspectives for diagnosis and treatment for neurobrucellosis.

研究领域: 微生物学 · 神经病学 · 代谢组学 · 临床化学
✓ 已验证 DOI PubMed 高影响因子
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