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乙胺丁醇
Microbiology Spectrum · 2026 · IF 4.1

Mutations in the ubiA gene are the major mechanism of ethambutol resistance in Mycobacterium avium

Yuwei Qiu,Xu Dong,Dan Cao,Xiuzhi Jiang,Zhongkang Ji,Pusheng Xu,Yi Li,Kaijing Xu,Ying Zhang

Mycobacterium avium-intracellulare complex (MAC) infections are the most common nontuberculous mycobacterial infections, and ethambutol (EMB) is one of the main therapeutic agents used to treat MAC infections. However, the EMB resistance profile and its resistance mechanisms in M. avium remain poorly understood. This study determined the minimum inhibitory concentration (MIC) of 40 M. avium clinical strains, revealing that 97.5% (39/40) of the strains were intermediate (MIC = 4 µg/mL) or resistant (MIC ≥ 8 µg/mL) to EMB. One susceptible clinical isolate strain 245 (MIC = 2 µg/mL) was picked for EMB-resistant mutant isolation, and a total of 121 resistant mutants were isolated and subjected to whole-genome sequencing or Sanger sequencing. Integrated analysis revealed that 94.21% (114/121) of the mutants carried mutations in the ubiA gene, which encodes decaprenylphosphoryl-β-D-5-phosphoribose (DPPR) synthase—an enzyme involved in cell wall biosynthesis that has been associated with high-level EMB resistance in Mycobacterium tuberculosis. Complementation with the wild-type ubiA gene restored EMB susceptibility in EMB-resistant mutants and clinical strain 322 (EMB MIC = 64 µg/mL) with ubiA mutation, reducing the MICs from 32 to 4 μg/mL and from 64 to 8 μg/mL, respectively. This study indicates that the ubiA mutation is the major mechanism of EMB resistance in M. avium, which should facilitate the development of molecular tests for rapid detection of resistance in this organism.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY · 2020 · IF 3.232

A Redox-induced Dual-mode Colorimetric and Fluorometric Method based on N-CDs and MnO2 for Determination of Isoniazid in Tablets and Plasma Samples

Kuanxia Ma,Lushan Liang,Xie Zhou,Weiguo Tan,Ou Hu,Zuanguang Chen

We develop a simple hydrothermal method to prepare a novel nitrogen-doped carbon dots (N-CDs) originated from green carbon source Liu-bao tea and ethylene diamine. The N-CDs emits strong and stable blue fluorescence (E m  = 440 nm) under the excitation wavelength of 350 nm with a quantum yield of 35%. And it is used as an excellent fluorescent output for the sensitive and visual dual-mode determination of isoniazid. The fluorescence of N-CDs is “turned off” first by manganese dioxide (MnO 2 ) nanosheets due to inner filter effect, MnO 2 nanosheets can also oxidize TMB (3,3',5,5'- tetramethylbenzidine) to blue oxTMB. Isoniazid, however, can reduce MnO 2 nanosheets to Mn 2+ , turning on the fluorescence again. The color of the solution fades from blue to colorless because less TMB can be oxidized. Under the optimal conditions, the dual-mode method has a satisfying linear relationship ranging from 2.0 to 120.0 μM with a limit of detection of 0.7 μM (S/N = 3). And it has been applied successfully to colorimetric and fluorescent determination of isoniazid in tablets and clinical plasma samples, with recoveries ranging from 94.0% to 102.4%. The properties of N-CDs and MnO 2 nanosheets were thoroughly characterized using TEM, FT-IR, XPS, AFM and fluorescence spectrophotometer, the quenching mechanism was also discussed.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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BMC Complementary Medicine and Therapies · 2025 ·Vol. 25 ·期 1 ·1-10 · IF 3.4

Essential Oils and their Active Constituents Effective against Non-growing Mycobacterium intracellulare

Jiang Xiuzhi,Cao Dan,Xu Bihan,Yuan Xin,Xiang Yanghui,Wu Tiantian,Zhang Ying

Background Mycobacterium intracellulare ( M. intracellulare ) is a common, slow-growing opportunistic pathogen that can cause chronic pulmonary and extrapulmonary infections. Despite its rising incidence, standard treatments are often ineffective in eradicating M. intracellulare , leading to prolonged treatment and high recurrence rates, likely due to persistence of non-growing bacteria. Although essential oils are known for their antimicrobial properties, their effects on M. intracellulare , particularly in its non-growing phase, have not been well studied. Methods We screened 151 essential oils to assess their antimicrobial activity against stationary-phase non-growing M. intracellulare . Essential oils with significant activity were further evaluated at different concentrations by MIC and drug exposure tests. Results Thirty-four essential oils were found to have activity at 5000 µg/mL, with 18 showing effectiveness at 1250 µg/mL. Six essential oils, Ajwain, Oregano, Palmarosa, Thyme, Mountain Savory, and Litsea Cubeba had the highest activity, achieving 100% bacterial clearance after one day exposure. Carvacrol, the key active component of Ajwain, Oregano, Thyme, Mountain Savory, eradicated stationary-phase bacteria at 310 µg/mL concentration within one day, while citronellol, the active component of Palmarosa, at 630 µg/mL achieved complete clearance after three day exposure. Conclusions We have newly identified several essential oils, including Ajwain, Oregano, Thyme, Mountain Savory, Palmarosa, and Litsea Cubeba and their active components such as carvacrol and citronellol, to have promising activity against M. intracellulare, and these findings may have implications for developing improved treatments for M. intracellulare infections.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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MOLECULAR NEUROBIOLOGY · 2025 ·Vol. 63 ·期 1 ·229 · IF 4.3

Ccn1 Mediates Pyroptosis and Purine Metabolism Pattern Shifts in a High-Uric Acid Microenvironment After Spinal Cord Injury

Zhang Zhiyang,Xu Nixi,Tao Zean,Liang Yun,Jin Lixia,Li Zhuoxuan,Cao Yuanwu,Jiang Chang,Chen Zixian

Spinal cord injury (SCI) often results in permanent functional loss due to the complexity of the post-SCI microenvironment, but the composition and functional dynamics of the post-SCI microenvironment remain poorly understood. We applied spatial metabolomics to detect metabolites within the spinal cord of SCI rats, revealing the existence of a high-uric acid (hUA) microenvironment. Subsequently, we utilized Bulk-RNA sequencing and single-cell RNA sequencing (scRNA-seq) analysis, identified elevated expression of Cellular communication network factor 1 (Ccn1) and alterations in purine metabolic patterns. To investigate the role of Ccn1 within this hUA microenvironment, PC12 cell line and Sprague–Dawley (SD) rats were used. In vitro , 4 groups were designed: Control ( n  = 6), UA (PC12 cells treated with 200 μM UA for 24 h) ( n  = 6), siCcn1 ( Ccn1 knockdown using small interfering RNA) ( n  = 6), and siCcn1  + UA ( n  = 6). In vivo groups: SCI (spinal cord injury only) ( n  = 6), hUA (induced hUA microenvironment by gavage with oxonic acid potassium salt 750 mg/kg and and ethambutol 250 mg/kg) ( n  = 6), AAV ( Ccn1 knockdown via adeno-associated virus) ( n  = 6), and AAV  + hUA ( n  = 6). Results showed that UA significantly reduced cellular aerobic respiration levels (Control vs UA: 62.87 ± 16.76 vs 17.09 ± 4.91 pmol/min, P  < 0.01) and induced pyroptosis, Ccn1 knockdown significantly improved aerobic respiration ( siCcn1  + UA vs UA: 46.45 ± 12.54 vs 17.09 ± 4.91 pmol/min, P  < 0.05) and reduced the level of pyroptosis. Total cellular ATP levels, the NAD⁺/NADH ratio, and proliferation capacity were also assessed. In vivo , Ccn1 knockdown significantly increased the Basso, Beattie, and Bresnahan (BBB) locomotor scores of animals on the 7 days post-injury ( AAV  + hUA vs hUA: 3.33 ± 0.52 vs 2.00 ± 0.63, P  < 0.05) and reduced neuronal pyroptosis. The hUA microenvironment upregulated Ccn1 expression, suppressed aerobic respiration, induced pyroptosis, and disrupted purine metabolism, Ccn1 knockdown reversed these biological processes, suggesting its potential as a therapeutic target for SCI.

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