期刊:
PHYSICAL CHEMISTRY CHEMICAL PHYSICS,2025年27(5):2828-2833 ISSN:1463-9076
通讯作者:
Liu, Xichun;Lin, YW
作者机构:
[Han, Hui; Pan, Aiqun; Lin, Ying-Wu; Liu, Xichun; Liu, XC] Univ South China, Sch Chem & Chem Engn, Hengyang 421001, Peoples R China.;[Gao, Shu-Qin; Lin, Ying-Wu] Univ South China, Lab Prot Struct & Funct, Hengyang 421001, Peoples R China.
通讯机构:
[Lin, YW ; Liu, XC] U;Univ South China, Sch Chem & Chem Engn, Hengyang 421001, Peoples R China.;Univ South China, Lab Prot Struct & Funct, Hengyang 421001, Peoples R China.
摘要:
Globin X is a newly discovered member of the globin family, while its structure and function are not fully understood. In this study, we performed protein modelling studies using Alphafold3 and molecular dynamics simulations, which suggested that the protein adopts a typical globin fold, with the formation of a potential disulfide bond of Cys65 and Cys141. To elucidate the role of this unique disulfide in protein structure and stability, we constructed a double mutant of C65S/C141S by mutating the two cysteine residues to serine. As suggested by protein mass, ultraviolet-visible (UV-Vis) and circular dichroism (CD) spectroscopy analyses, the potential disulfide bond has minimal effect on the overall protein structure, but its absence reduces the protein stability. Electron paramagnetic resonance (EPR) analysis also revealed an increase in the proportion of high-spin state heme iron, which accelerates the rate of heme degradation in reaction with H(2)O(2). This study highlights the critical role of the Cys65-Cys141 in maintaining the stability of globin X and the bis-His heme coordination state, providing insights into the structure-function relationship of the newly discovered globin.
摘要:
The rapid and selective identification of microorganisms is of great significance for clinical therapy applications. To develop high performance probes for microbe determination, we systemically constructed series aggregation-induced emission (AIE) luminogens by modulating the structural planarity, the basicity of functional group, the length of linker moiety and the hydrophobicity based on our previous work. The detail structure-property relationship study based on experimental and theoretical observation revealed that: i) the planar skeleton is essential for probe insertion towards the cell wall via van n der Waals' force. ii) the basic function group enable the anchoring on the membrane by binding with acidic biomolecules. iii) the shortened alkyl chain is in favor of the efficient binding of basic groups with microbes and endows the desirable hydrophobicity. Based on the developed probes, the successful detection of the pathogens in clinic samples was achieved in highly sensitive and simple way. This work provides a reliable strategy for designing intelligent luminogens for microorganism discrimination and identification in efficient and sensitive way for in vitro diagnosis applications, especially point-of-care testing (POCT).
The rapid and selective identification of microorganisms is of great significance for clinical therapy applications. To develop high performance probes for microbe determination, we systemically constructed series aggregation-induced emission (AIE) luminogens by modulating the structural planarity, the basicity of functional group, the length of linker moiety and the hydrophobicity based on our previous work. The detail structure-property relationship study based on experimental and theoretical observation revealed that: i) the planar skeleton is essential for probe insertion towards the cell wall via van n der Waals' force. ii) the basic function group enable the anchoring on the membrane by binding with acidic biomolecules. iii) the shortened alkyl chain is in favor of the efficient binding of basic groups with microbes and endows the desirable hydrophobicity. Based on the developed probes, the successful detection of the pathogens in clinic samples was achieved in highly sensitive and simple way. This work provides a reliable strategy for designing intelligent luminogens for microorganism discrimination and identification in efficient and sensitive way for in vitro diagnosis applications, especially point-of-care testing (POCT).
期刊:
Molecular and Cellular Biochemistry,2025年480(4):2143-2157 ISSN:0300-8177
通讯作者:
Jing Wang
作者机构:
[Tingting Jiang] Department of Clinical Laboratory, Hengyang Medical School, the Affiliated Nanhua Hospital, University of South China, Hengyang, 421000, China;[Qun Zeng] Department of Biochemistry and Molecular Biology, Hengyang Medical School, University of South China, Hengyang, 421000, China;[Jing Wang] Hunan Provincial Key Laboratory of the Traditional Chinese Medicine Agricultural Biogenomics, Changsha Medical University, Changsha, 410219, China. 805598382@qq.com;[Jing Wang] Hunan Provincial University Key Laboratory of the Fundamental and Clinical Research On Functional Nucleic Acid, Changsha Medical University, Changsha, 410219, China. 805598382@qq.com;[Jing Wang] The First Clinical College, Changsha Medical University, Changsha, 410219, China. 805598382@qq.com
通讯机构:
[Jing Wang] H;Hunan Provincial Key Laboratory of the Traditional Chinese Medicine Agricultural Biogenomics, Changsha Medical University, Changsha, China<&wdkj&>Hunan Provincial University Key Laboratory of the Fundamental and Clinical Research On Functional Nucleic Acid, Changsha Medical University, Changsha, China<&wdkj&>The First Clinical College, Changsha Medical University, Changsha, China
摘要:
FHL2 (Four-and-a-half LIM domain protein 2) is a crucial factor involved in cardiac morphogenesis, the process by which the heart develops its complex structure. It is expressed in various tissues during embryonic development, including the developing heart, and has been shown to play important roles in cell proliferation, differentiation, and migration. FHL2 interacts with multiple proteins to regulate cardiac development as a coactivator or a corepressor. It is involved in cardiac specification and determination of cell fate, cardiomyocyte growth, cardiac remodeling, myofibrillogenesis, and the regulation of HERG channels. Targeting FHL2 has therapeutic implications as it could improve cardiac function, control arrhythmias, alleviate heart failure, and maintain cardiac integrity in various pathological conditions. The identification of FHL2 as a signature gene in atrial fibrillation suggests its potential as a diagnostic marker and therapeutic target for this common arrhythmia.
摘要:
The sensitive detection of the radioactive thorium (Th) ion with an oxidation state of +4 (Th(4+)) is of great significance for environmental protection and life safety. In this study, five fluorescence sensors with regulated donor-acceptor (D-A) interactions were constructed for Th(4+) detection based on intramolecular charge transfer and aggregation-induced emission mechanisms. Among the developed sensors, TPE-D bearing electron-deficient π-bridge and weak D-A interactions presented ratiometric fluorescence detection behavior toward Th(4+) in aqueous solution due to its aggregation-induced emission characteristics and unique D-A-D structures. Moreover, TPE-D showed excellent selectivity and sensitivity for Th(4+) detection, and the detection limit was as low as 8.1 × 10(-8) M. The sensing mechanism observation revealed that Th(4+) could coordinate with the hydroxyl, imine, and carbonyl groups of TPE-D accompanied by an electron transfer process. In addition, TPE-D could selectively be enriched in the lysosome. Both the detection of Th(4+) in the lysosome and liver of mice and zebrafish were realized based on this strategy, and a mobile-assisted detection approach toward Th(4+) in actual water samples was also established with high sensitivity. This is the first report for Th(4+) detection in organelles and organs, which provides a great significance and reliable strategy for radionuclide toxicology detection and analysis applications.
作者机构:
[Zhou, Daming; Qin, AJ; Zhang, Guiquan; Qin, Anjun] South China Univ Technol, Guangdong Prov Key Lab Luminescence Mol Aggregates, State Key Lab Luminescent Mat & Devices, Guangzhou 510640, Peoples R China.;[Tang, Ben Zhong] Chinese Univ Hong Kong, Shenzhen Inst Aggregate Sci & Technol, Sch Sci & Engn, Shenzhen CUHK Shenzhen, Shenzhen 518172, Peoples R China.;[Hu, Rong; Hu, R] Univ South China, Sch Chem & Chem Engn, Hengyang 421001, Peoples R China.
通讯机构:
[Qin, AJ ] S;[Tang, BZ ] C;[Hu, R ] U;South China Univ Technol, Guangdong Prov Key Lab Luminescence Mol Aggregates, State Key Lab Luminescent Mat & Devices, Guangzhou 510640, Peoples R China.;Chinese Univ Hong Kong, Shenzhen Inst Aggregate Sci & Technol, Sch Sci & Engn, Shenzhen CUHK Shenzhen, Shenzhen 518172, Peoples R China.
摘要:
Fluorescence imaging technology is playing increasing roles in modern personalized and precision medicine. Thanks to their excellent photophysical properties, organic luminogens featuring aggregation-induced emission (AIE) characteristics (AIEgens) have attracted considerable attention over the past two decades. Because of their superior biocompatibility, ease of processing and functionalization, excellent water solubility, high responsiveness, and exceptional signal-to-noise ratio (SNR) for biotargets, AIE bioconjugates, formed by covalently linking AIEgens with biomolecules, have emerged as an ideal candidate for bioapplications. In this review, we summarize the progress in preparation, properties, and application of AIE bioconjugates in the last five years. Moreover, the challenges and opportunities of AIE bioconjugates are also briefly discussed.
期刊:
International Journal of Biological Macromolecules,2025年309(Pt 1):142768 ISSN:0141-8130
通讯作者:
Xu, JK
作者机构:
[Zhao, Sijia; Li, Dong; Xu, Jiakun; Wang, Fang; Wang, Jinghan] Chinese Acad Fishery Sci, Yellow Sea Fisheries Res Inst, State Key Lab Mariculture Biobreeding & Sustainabl, Key Lab Sustainable Dev Polar Fisheries,Minist Agr, Qingdao 266071, Peoples R China.;[Zhao, Sijia; Wang, Jinghan] Ocean Univ China, Coll Food Sci & Engn, Qingdao Marine Sci & Technol Ctr, Lab Marine Drugs & Bioprod, Qingdao 266003, Peoples R China.;[Shoji, Osami] Nagoya Univ, Grad Sch Sci, Dept Chem, Furo Cho,Chikusa Ku, Nagoya 4648602, Japan.;[Lin, Yingwu] Univ South China, Sch Chem & Chem Engn, Hengyang 421001, Peoples R China.
通讯机构:
[Xu, JK ] C;Chinese Acad Fishery Sci, Yellow Sea Fisheries Res Inst, State Key Lab Mariculture Biobreeding & Sustainabl, Key Lab Sustainable Dev Polar Fisheries,Minist Agr, Qingdao 266071, Peoples R China.
关键词:
Lignin;O-demethylation;P450BM3
摘要:
The enzymatic demethylation of aromatic compounds presents a major challenge in the valorization of lignin. The main goal was to develop an efficient artificial peroxygenase system combining engineered P450BM3 with AldO (sugar alcohol oxidase) and DFSM (dual function small molecule) for the regioselective O -demethylation of lignin-derived aromatic ethers. P450BM3 serves as a versatile biocatalyst, and its engineered variants demonstrate expanded substrate promiscuity toward non-native substrates. AldO, served as the H 2 O 2 in situ generation system. The DFSM, a rationally designed catalytic auxiliary, facilitates precise control of enzymatic reactions and enhances the efficiency of O -demethylation. We hypothesize that by combining P450BM3 with AldO and DFSM, we can better control the generation of H 2 O 2 and direct the enzymatic system toward efficient O -demethylation. The engineered P450BM3 F87A/V78A/T268D/A328F mutant achieved a TON of 1895 ± 4 for guaiacol, more than double that of the native P450BM3/H 2 O 2 system (TON = 872 ± 7). Moreover, the F87A/T268D mutant efficiently catalyzed double-demethylation of syringol, achieving the highest turnover number (TON) of 483 ± 7. This DFSM-assisted P450BM3/AldO system represents a significant advancement in the biocatalytic degradation of lignin and offers a cost-effective and scalable alternative to traditional NADPH-dependent P450 monooxygenases. Our findings open new pathways for sustainable biotechnological applications in lignin valorization and aromatic compound catabolism.
The enzymatic demethylation of aromatic compounds presents a major challenge in the valorization of lignin. The main goal was to develop an efficient artificial peroxygenase system combining engineered P450BM3 with AldO (sugar alcohol oxidase) and DFSM (dual function small molecule) for the regioselective O -demethylation of lignin-derived aromatic ethers. P450BM3 serves as a versatile biocatalyst, and its engineered variants demonstrate expanded substrate promiscuity toward non-native substrates. AldO, served as the H 2 O 2 in situ generation system. The DFSM, a rationally designed catalytic auxiliary, facilitates precise control of enzymatic reactions and enhances the efficiency of O -demethylation. We hypothesize that by combining P450BM3 with AldO and DFSM, we can better control the generation of H 2 O 2 and direct the enzymatic system toward efficient O -demethylation. The engineered P450BM3 F87A/V78A/T268D/A328F mutant achieved a TON of 1895 ± 4 for guaiacol, more than double that of the native P450BM3/H 2 O 2 system (TON = 872 ± 7). Moreover, the F87A/T268D mutant efficiently catalyzed double-demethylation of syringol, achieving the highest turnover number (TON) of 483 ± 7. This DFSM-assisted P450BM3/AldO system represents a significant advancement in the biocatalytic degradation of lignin and offers a cost-effective and scalable alternative to traditional NADPH-dependent P450 monooxygenases. Our findings open new pathways for sustainable biotechnological applications in lignin valorization and aromatic compound catabolism.
摘要:
An activatable photosensitizer with a reaction‐tunable donor/acceptor push‐pull electronic effect is designed and developed, which shows high sensitivity toward nitric oxide (NO) NO with the formation of triazole segment. Moreover, the turn‐on PDT behavior and endoplasmic reticulum (ER) targeting ability enable the developed photosensitizer good inhibition effect toward tumor cells both in vitro and in vivo, which presents high promise for precise tumor therapy in practical. Abstract Photodynamic therapy (PDT) is a powerful strategy for tumor therapy with noninvasiveness and desirable efficacy. However, the phototoxicity of photosensitizer after the post‐PDT is the major obstacle limiting the clinic applications. Herein, a nitric oxide (NO)‐activatable photosensitizer is reported with turn‐on PDT behavior and endoplasmic reticulum (ER) targeting ability for precise tumor therapy. Four o‐thiophenediamine derivatives with reaction‐tunable donor/acceptor push‐pull electronic effect are established, and the systematic structure and property relationship observation reveals the following features: 1) the reactivity against NO can be improved by enhancing the electron density and further facilitated upon photo‐irradiation. 2) the reactivity with NO enables the improved intramolecular charge transfer process with the evoking of photosensitizing effect. 3) only o‐thiophenediamine derivative with ER enrichment behavior exhibited cancer cell ablation effect compared to photosensitizers localized in lysosome and lipid droplet. Thus, the efficient inhibition of cancer cells both in vitro and in vivo is realized based on the photo‐controlled PDT strategy. This work provides more insights into developing promising activatable photosensitizers for advanced therapy based on tumor microenvironment trigger.
作者机构:
[Zhang, Yuexin; Li, Ye; Yin, Mingxue; Li, Chunquan; Liu, Liyuan; Zhang, Guorui; Zhang, Jianing; Song, Chao] Univ South China, Affiliated Hosp 1, Hengyang 421001, Hunan, Peoples R China.;[Zhang, Yuexin; Li, Ye; Yin, Mingxue; Li, Chunquan; Liu, Liyuan; Zhang, Guorui; Zhang, Jianing; Song, Chao] Univ South China, Hengyang Med Sch, Natl Hlth Commiss Key Lab Birth Defect Res & Preve, Hengyang 421001, Hunan, Peoples R China.;[Zhang, Yuexin; Li, Ye; Yin, Mingxue; Li, Chunquan; Liu, Liyuan; Zhang, Guorui; Zhang, Jianing; Song, Chao] Univ South China, Hunan Prov Key Lab Multiomics&Artificial Intellige, Hengyang 421001, Hunan, Peoples R China.;[Li, Ye; Yin, Mingxue; Li, Chunquan; Liu, Liyuan; Zhang, Guorui] Univ South China, Sch Basic Med Sci, Hengyang Med Sch, Dept Biochem & Mol Biol, Hengyang 421001, Hunan, Peoples R China.;[Li, Chunquan; Song, Chao] Univ South China, Sch Comp, Hengyang 421001, Hunan, Peoples R China.
通讯机构:
[Li, CQ ] U;[Guo, MZ ] B;Univ South China, Affiliated Hosp 1, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Hengyang Med Sch, Natl Hlth Commiss Key Lab Birth Defect Res & Preve, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Hunan Prov Key Lab Multiomics&Artificial Intellige, Hengyang 421001, Hunan, Peoples R China.
摘要:
It is challenging to identify regulatory transcriptional regulators (TRs), which control gene expression via regulatory elements and epigenomic signals, in context-specific studies on the onset and progression of diseases. The use of large-scale multi-omics epigenomic data enables the representation of the complex epigenomic patterns of control of the regulatory elements and the regulators. Herein, we propose Transcription Regulator Activity Prediction Tool (TRAPT), a multi-modality deep learning framework, which infers regulator activity by learning and integrating the regulatory potentials of target gene cis-regulatory elements and genome-wide binding sites. The results of experiments on 570 TR-related datasets show that TRAPT outperformed state-of-the-art methods in predicting the TRs, especially in terms of forecasting transcription co-factors and chromatin regulators. Moreover, we successfully identify key TRs associated with diseases, genetic variations, cell-fate decisions, and tissues. Our method provides an innovative perspective on identifying TRs by using epigenomic data. Here, the authors propose Transcription Regulator Activity Prediction Tool (TRAPT), a multi-modality deep learning framework, which infers regulator activity by learning and integrating the regulatory potentials of target gene cis-regulatory elements and genome-wide binding sites.
摘要:
Chloroanilines represent a class of persistent and highly toxic environmental pollutants, posing significant challenges for green remediation strategies. While P450BM3 monooxygenases are renowned for their ability to catalyze the monooxidation of inert C-H bonds, costly NAD(P)H and complex electron transport systems required for P450BM3 catalysis limit their practical applications. This study pioneers the development of innovative artificial biocatalysts by strategically engineering the active site of P450BM3. Specifically, the substitution of the highly conserved threonine 268 with aspartic acid effectively induces peroxygenase activity, allowing for enhanced catalytic efficiency. Remarkably, the engineered P450BM3 mutants achieved degradation rates of 98.38–99.18 % for five chloroanilines (4-chloroaniline, 2-chloroaniline, 2,4-dichloroaniline, 3,4-dichloroaniline, and 3,5-dichloroaniline) in just 10–15 min, all without the need for NAD(P)H or dual-functional small molecules. Comprehensive degradation mechanism analysis via UPLC-MS corroborated the remarkable performance of these biocatalysts. This research not only demonstrates a novel approach for engineering P450 monooxygenases to exhibit peroxygenase activity but also significantly broadens their potential applications in synthetic chemistry and synthetic biology, paving the way for greener and more sustainable remediation technologies.
Chloroanilines represent a class of persistent and highly toxic environmental pollutants, posing significant challenges for green remediation strategies. While P450BM3 monooxygenases are renowned for their ability to catalyze the monooxidation of inert C-H bonds, costly NAD(P)H and complex electron transport systems required for P450BM3 catalysis limit their practical applications. This study pioneers the development of innovative artificial biocatalysts by strategically engineering the active site of P450BM3. Specifically, the substitution of the highly conserved threonine 268 with aspartic acid effectively induces peroxygenase activity, allowing for enhanced catalytic efficiency. Remarkably, the engineered P450BM3 mutants achieved degradation rates of 98.38–99.18 % for five chloroanilines (4-chloroaniline, 2-chloroaniline, 2,4-dichloroaniline, 3,4-dichloroaniline, and 3,5-dichloroaniline) in just 10–15 min, all without the need for NAD(P)H or dual-functional small molecules. Comprehensive degradation mechanism analysis via UPLC-MS corroborated the remarkable performance of these biocatalysts. This research not only demonstrates a novel approach for engineering P450 monooxygenases to exhibit peroxygenase activity but also significantly broadens their potential applications in synthetic chemistry and synthetic biology, paving the way for greener and more sustainable remediation technologies.
摘要:
Aptamers have recently become novel probes for biosensors because of their good biocompatibility, strong specificity, and high sensitivity. Biosensors based on peptides or nucleic acid aptamers are used in implantable and wearable devices owing to their ease of synthesis and economic efficiency. Simultaneously, amphoteric ionic peptides are being explored as antifouling layers for biosensors resistant to interference from extraneous proteins in serum. Thus, this paper reviews recently developed aptamer-based biosensors and introduces peptide- and nucleic acid-based biosensors, while focusing on the three primary classes of biosensors: electrochemical sensors, fluorescent or colorimetric biosensors, and electroluminescent sensors. Furthermore, we summarize their general construction strategies, describe specific electrochemical sensors that use peptides as an antipollution layer, and elucidate their advantages.
期刊:
Biosensors and Bioelectronics,2025年267:116857 ISSN:0956-5663
通讯作者:
Jikai Wang
作者机构:
[Wang, Jikai] Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Institute of Pharmacy & Pharmacology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, PR China. Electronic address: jkwang@hnu.edu.cn;[Mo, Ziyi; Xie, Zhulan] Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Institute of Pharmacy & Pharmacology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, PR China;[Xie, Haitao] Department of Clinical Laboratory Medicine, Institution of Microbiology and Infectious Diseases, Hunan Province Clinical Research Center for Accurate Diagnosis and Treatment of High-incidence Sexually Transmitted Diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, PR China;[Wang, Weiguo] Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Institute of Pharmacy & Pharmacology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, PR China. Electronic address: wang901234@163.com;[Zhu, Yanli] School of Chemistry and Chemical Engineering, University of South China, Hengyang, Hunan, 421001, PR China. Electronic address: zhuyanli666@hnu.edu.cn
通讯机构:
[Jikai Wang] H;Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Institute of Pharmacy & Pharmacology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, PR China
摘要:
The development of enzyme activity analysis methods is critical for precise and rapid assessments of enzyme activity levels within biological systems, facilitating a more profound comprehension of physiological functions and disease mechanisms. Alkaline phosphatase (ALP) participates in various physiological processes involving phosphate ester hydrolysis. Altered ALP activity levels are often indicative of different diseases, underscoring the necessity for accurate ALP activity determination in medical diagnostics. This study innovatively applies turbidity as a physical variable, proposing a turbidimetric sensor based on an enhanced ammonium molybdate reagent for phosphate analysis. By integrating this with the ALP substrate p-nitrophenyl phosphate, a turbidimetric sensor was devised and employed for ALP activity analysis. The proposed turbidimetric sensor demonstrated high sensitivity both for phosphate (0.18 μmol/L) and ALP activity (0.03 mU/mL) assay. In practical applications, this turbidimetric sensor has been effectively employed to detect ALP activity in mouse feces, showcasing its potential for auxiliary diagnosis of inflammatory bowel disease. Significantly, this novel turbidity-based approach offers not only swift and straightforward procedures but also remarkable portability and cost-efficiency. Requiring solely a handheld turbidimeter and eliminating the need for bulky instruments, this approach holds significant potential for point-of-care testing applications.
The development of enzyme activity analysis methods is critical for precise and rapid assessments of enzyme activity levels within biological systems, facilitating a more profound comprehension of physiological functions and disease mechanisms. Alkaline phosphatase (ALP) participates in various physiological processes involving phosphate ester hydrolysis. Altered ALP activity levels are often indicative of different diseases, underscoring the necessity for accurate ALP activity determination in medical diagnostics. This study innovatively applies turbidity as a physical variable, proposing a turbidimetric sensor based on an enhanced ammonium molybdate reagent for phosphate analysis. By integrating this with the ALP substrate p-nitrophenyl phosphate, a turbidimetric sensor was devised and employed for ALP activity analysis. The proposed turbidimetric sensor demonstrated high sensitivity both for phosphate (0.18 μmol/L) and ALP activity (0.03 mU/mL) assay. In practical applications, this turbidimetric sensor has been effectively employed to detect ALP activity in mouse feces, showcasing its potential for auxiliary diagnosis of inflammatory bowel disease. Significantly, this novel turbidity-based approach offers not only swift and straightforward procedures but also remarkable portability and cost-efficiency. Requiring solely a handheld turbidimeter and eliminating the need for bulky instruments, this approach holds significant potential for point-of-care testing applications.
摘要:
Multidrug resistance of tumor cells has greatly limited the chemotherapy effect. The development of reliable strategies to deal with tumor multidrug resistance is highly desirable for tumor therapy. In this work, a near-infrared II (NIR II) luminogen was rationally designed and prepared, which could act as a photothermal reagent to reverse the drug resistance of tumor cells by reducing the related protein expression, achieving a high inhibition efficiency with the synergistic effect of chemotherapeutic drugs. By the selection of a strong electron-withdrawing unit, the emission peak of the luminogen could reach 973 nm. Moreover, this luminogen shows outstanding photothermal conversion ability and improved thermal stability compared to ICG. Notably, after the photothermal treatment of drug-resistant tumor cells by the NIR II luminogen, the antitumor efficiency of chemotherapeutic drugs, including paclitaxel, cis-platinum, and doxorubicin, was significantly enhanced. The mechanism exploration revealed that drug resistance-related proteins were remarkably reduced, making the cells more sensitive toward drugs. Thus, this strategy demonstrated a promising and reliable approach to reverse the drug resistance of tumor cells for efficient tumor inhibition in the clinic.
通讯机构:
[Liao, S ] U;Univ South China, Sch Chem & Chem Engn, Hengyang 421001, Hunan, Peoples R China.
摘要:
By utilizing carboxylated multiwalled carbon nanotubes (MWCNT-COOH) to strengthen the interaction between the electrode and the analytes and improve the conductivity of the composite material and in conjunction with the superior catalytic properties of copper-based metal-organic framework (MOFs), a novel electrochemical sensor was fabricated from a Cu-MOF/MWCNT-COOH composite, specifically designed for the simultaneous and distinct detection of ascorbic acid (AA) and dopamine (DA). Electrochemical analyses were conducted on the innovative Cu-MOF/MWCNT-COOH electrode through both CV and DPV, revealing unique electrochemical behaviors for AA and DA. The sensor not only showed exceptional electrocatalytic properties but also distinguished itself by its broad dynamic response ranges, covering concentrations from 3 to 1800 μM for AA and from 2 to 180 μM for DA, with detection limits (S/N = 3) of 3.00 μM for AA and 0.32 μM for DA. Furthermore, this electrochemical detection platform exhibited robust reproducibility and selectivity. Examinations of serum samples yielded the recovery rates of AA and DA which were 101.9% and 102.1%, respectively, confirming the sensor's capability to perform reliably under varied biological conditions. The findings confirm the sensor's potential of the proposed method for the simultaneous, sensitive, and reliable detection of AA and DA. In conclusion, the electrochemical sensor has a promising potential for practical applications.
摘要:
Spatially resolved transcriptomics technologies potentially provide the extra spatial position information and tissue image to better inferspatial cell-cell interactions (CCIs) in processes such as tissue homeostasis, development, and disease progression. However, methods for effectively integrating spatial multimodal data to infer CCIs are still lacking. Here, the authors propose a deep learning method for integrating features through co-convolution, called SpaGraphCCI, to effectively integrate data from different modalities of SRT by projecting gene expression and image feature into a low-dimensional space. SpaGraphCCI can achieve significant performance on datasets from multiple platforms including single-cell resolution datasets (AUC reaches 0.860-0.907) and spot resolution datasets (AUC ranges from 0.880 to 0.965). SpaGraphCCI shows better performance by comparing with the existing deep learning-based spatial cell communication inference methods. SpaGraphCCI is robust to high noise and can effectively improve the inference of CCIs. We test on a human breast cancer dataset and show that SpaGraphCCI can not only identify proximal cell communication but also infer new distal interactions. In summary, SpaGraphCCI provides a practical tool that enables researchers to decipher spatially resolved cell-cell communication based on spatial transcriptome data.
期刊:
Biosensors and Bioelectronics,2025年267:116805 ISSN:0956-5663
通讯作者:
Huanxiang Yuan
作者机构:
[Yi Wang; Yue Zhao; Yuying Zhang] Department of Chemistry, College of Chemistry and Materials Engineering, Beijing Technology and Business University, Beijing, 100048, PR China;[Rong Hu] School of Chemistry and Chemical Engineering, University of South China, Hengyang, 421001, PR China;[Huanxiang Yuan] Department of Chemistry, College of Chemistry and Materials Engineering, Beijing Technology and Business University, Beijing, 100048, PR China. Electronic address: yhx@iccas.ac.cn
通讯机构:
[Huanxiang Yuan] D;Department of Chemistry, College of Chemistry and Materials Engineering, Beijing Technology and Business University, Beijing, 100048, PR China
关键词:
Aggregation-induced emission;Biosensing;Cells;Macromolecules;Metal ions;Microbes;Small chemical molecules
摘要:
In recent years, aggregation-induced emission (AIE) materials have gained significant attention and have been developed for various applications in different fields including biomedical research, chemical analysis, optoelectronic devices, materials science, and nanotechnology. AIE is a unique luminescence phenomenon, and AIEgens are fluorescent moieties with relatively twisted structures that can overcome the aggregation-caused quenching (ACQ) effect. Additionally, AIEgens offer advantages such as non-washing properties, deep tissue penetration, minimal damage to biological structures, high signal-to-noise ratio, and excellent photostability. Fluorescent probes with AIE characteristics exhibit high sensitivity, short response time, simple operation, real-time detection capability, high selectivity, and excellent biocompatibility. As a result, they have been widely applied in cellular imaging, luminescent sensing, detection of physiological abnormalities in the human body, as well as early diagnosis and treatment of diseases. This review provides a comprehensive summary and discussion of the progress over the past four years regarding the detection of metal ions, small chemical molecules, biomacromolecules, microbes, and cells based on AIE materials, along with discussing their potential applications and future development prospects.
In recent years, aggregation-induced emission (AIE) materials have gained significant attention and have been developed for various applications in different fields including biomedical research, chemical analysis, optoelectronic devices, materials science, and nanotechnology. AIE is a unique luminescence phenomenon, and AIEgens are fluorescent moieties with relatively twisted structures that can overcome the aggregation-caused quenching (ACQ) effect. Additionally, AIEgens offer advantages such as non-washing properties, deep tissue penetration, minimal damage to biological structures, high signal-to-noise ratio, and excellent photostability. Fluorescent probes with AIE characteristics exhibit high sensitivity, short response time, simple operation, real-time detection capability, high selectivity, and excellent biocompatibility. As a result, they have been widely applied in cellular imaging, luminescent sensing, detection of physiological abnormalities in the human body, as well as early diagnosis and treatment of diseases. This review provides a comprehensive summary and discussion of the progress over the past four years regarding the detection of metal ions, small chemical molecules, biomacromolecules, microbes, and cells based on AIE materials, along with discussing their potential applications and future development prospects.
作者机构:
[Yadan Yang; Weikang Zhang; Fang Wang] State Key Laboratory of Mariculture Biobreeding and Sustainable Goods, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266237, China;[Yadan Yang; Weikang Zhang] College of Marine Science and Biological Engineering, Qingdao University of Science and Technology, Qingdao 266042, China;[Xiangmin Meng] College of Marine Science and Biological Engineering, Qingdao University of Science and Technology, Qingdao 266042, China. Electronic address: mengxiangmin@qust.edu.cn;[Ying-Wu Lin] School of Chemistry and Chemical Engineering, University of South China, Hengyang 421001, China. Electronic address: ywlin@usc.edu.cn;[Jiakun Xu] State Key Laboratory of Mariculture Biobreeding and Sustainable Goods, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266237, China. Electronic address: xujk@ysfri.ac.cn
通讯机构:
[Xiangmin Meng] C;[Ying-Wu Lin; Jiakun Xu] S;School of Chemistry and Chemical Engineering, University of South China, Hengyang 421001, China<&wdkj&>State Key Laboratory of Mariculture Biobreeding and Sustainable Goods, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266237, China<&wdkj&>College of Marine Science and Biological Engineering, Qingdao University of Science and Technology, Qingdao 266042, China
摘要:
A novel artificial peroxidase has been developed for the efficient degradation of the non-steroidal anti-inflammatory drug meloxicam by combining computer simulation and genetic engineering techniques. The results showed that the artificial peroxidase was able to completely degrade meloxicam within 90 s, with a degradation rate of 100 %, which was much higher than that of natural lacquer (46 %). The reaction time of the artificial enzyme was significantly shorter than that of natural peroxidase (10 min) and laccase (48 h). Further studies showed that the amino acid arrangement of the active site of the protein plays an important role in the catalytic performance. The degradation pathway of meloxicam was revealed using UPLC-MS analysis. In vitro toxicity assay showed complete disappearance of toxicity after meloxicam degradation. Therefore, the biocatalytic system proved to be an effective route for the green degradation of meloxicam with important application potential.
A novel artificial peroxidase has been developed for the efficient degradation of the non-steroidal anti-inflammatory drug meloxicam by combining computer simulation and genetic engineering techniques. The results showed that the artificial peroxidase was able to completely degrade meloxicam within 90 s, with a degradation rate of 100 %, which was much higher than that of natural lacquer (46 %). The reaction time of the artificial enzyme was significantly shorter than that of natural peroxidase (10 min) and laccase (48 h). Further studies showed that the amino acid arrangement of the active site of the protein plays an important role in the catalytic performance. The degradation pathway of meloxicam was revealed using UPLC-MS analysis. In vitro toxicity assay showed complete disappearance of toxicity after meloxicam degradation. Therefore, the biocatalytic system proved to be an effective route for the green degradation of meloxicam with important application potential.
作者机构:
[Han, Hui; Lin, Ying-Wu; Wang, Yanfei; Liu, Xichun] Univ South China, Sch Chem & Chem Engn, Hengyang 421001, Peoples R China.;[Yu, Lu] Univ Sci & Technol China, Div Life Sci & Med, Hefei 230026, Peoples R China.;[Gao, Shu-Qin; Lin, Ying-Wu] Univ South China, Hengyang Med Sch, Hengyang 421001, Peoples R China.
通讯机构:
[Lin, YW ] U;Univ South China, Sch Chem & Chem Engn, Hengyang 421001, Peoples R China.;Univ South China, Hengyang Med Sch, Hengyang 421001, Peoples R China.
摘要:
The human hemoglobin subunit mu (Hb-mu) has been identified as a potential biomarker for alpha-thalassemia. However, little structural and functional information is available for this subunit. Here, we have overexpressed and purified a double mutant of C49S/C104S Hb-mu and solved its X-ray crystal structure. It adopts a typical protein fold of the globins, similar to that of the alpha-subunit. The structure also reveals that the protein undergoes self-oxidation of Met62 in the heme distal site, producing the form of sulfoxide (Met-SO). The property and function have also been studied by spectroscopy, which shows that the protein has considerable peroxidase activity due to the presence of a catalytic His-Arg pair in the heme distal site. The structure-function relationship of Hb-mu obtained in this study may provide useful insights into Hb-related diseases.
摘要:
Plastic pollution has emerged as a significant global concern due to its potential threat to human health. The advancement of self-powered photoelectrochemical (PEC) sensors based on dual-photoelectrode presents ongoing challenges. The photoanode PEC analysis method is normally employed due to its remarkable photocurrent and low detection limit; however, it exhibits limited anti-interference capability in real sample detection. Conversely, the photocathode analysis method demonstrates excellent anti-interference detection capabilities, effectively mitigating the inherent disadvantages associated with the photoanode. Consequently, we have developed a self-powered PEC portable sensor that integrates both a photocathode and a photoanode, enabling accurate, sensitive, and convenient detection of polystyrene microplastics (PS MPs). Under optimal conditions, the sensor has a detection limit of 0.09 μg/mL, with a linear range from 0.5 to 1000 μg/mL. The method has good anti-interference ability to heavy metal ions and organics. In the presence of interfering substances, the accuracy can be maintained at over 97%. In addition, the sensor has demonstrated excellent performance in complex aquatic environments, providing an innovative design strategy for constructing PEC sensors aimed at detecting PS MPs.
Plastic pollution has emerged as a significant global concern due to its potential threat to human health. The advancement of self-powered photoelectrochemical (PEC) sensors based on dual-photoelectrode presents ongoing challenges. The photoanode PEC analysis method is normally employed due to its remarkable photocurrent and low detection limit; however, it exhibits limited anti-interference capability in real sample detection. Conversely, the photocathode analysis method demonstrates excellent anti-interference detection capabilities, effectively mitigating the inherent disadvantages associated with the photoanode. Consequently, we have developed a self-powered PEC portable sensor that integrates both a photocathode and a photoanode, enabling accurate, sensitive, and convenient detection of polystyrene microplastics (PS MPs). Under optimal conditions, the sensor has a detection limit of 0.09 μg/mL, with a linear range from 0.5 to 1000 μg/mL. The method has good anti-interference ability to heavy metal ions and organics. In the presence of interfering substances, the accuracy can be maintained at over 97%. In addition, the sensor has demonstrated excellent performance in complex aquatic environments, providing an innovative design strategy for constructing PEC sensors aimed at detecting PS MPs.
摘要:
Lon peptidase 1 (LONP1), a member of the AAA + family, is essential for maintaining mitochondrial function. Recent studies have revealed that LONP1 serves as a multifunctional enzyme, acting not only as a protease but also as a molecular chaperone, interacting with mitochondrial DNA (mtDNA), and playing roles in mitochondrial dynamics, oxidative stress, cellular respiration, and energy metabolism. LONP1 is evolutionarily highly conserved, and mutations or dysfunctions in LONP1 can lead to diseases. There is growing evidence linking LONP1 to various human diseases, such as tumors, neurodegenerative diseases, and heart diseases. This review discusses the discovery, molecular structure, subcellular localization, tissue distribution, and mitochondrial function of LONP1. Furthermore, it summarizes the associations between LONP1 and tumors, neurodegenerative diseases, and heart diseases, exploring its role in different diseases and potential molecular mechanisms. It also analyzes the regulatory effects of related inhibitors and agonists on LONP1. Considering the pleiotropic effects of LONP1, the study of LONP1 is crucial to understanding the relevant pathophysiological processes and developing strategies to modulate and control these related diseases.
作者机构:
[Li, Ye; Zhang, Yuexin; Li, Chunquan; Zhao, Yu; Huang, Xuemei; Xie, Liyuan; Zhang, Guorui; Zhao, Jun; Fan, Shifan; Song, Chao] Univ South China, Hengyang Med Sch, Affiliated Hosp 1, Hengyang 421001, Hunan, Peoples R China.;[Li, Ye; Zhang, Yuexin; Li, Chunquan; Zhao, Yu; Huang, Xuemei; Xie, Liyuan; Zhang, Guorui; Zhao, Jun; Fan, Shifan; Song, Chao] Univ South China, Hengyang Med Sch, MOE Key Lab Rare Pediat Dis, Hengyang 421001, Hunan, Peoples R China.;[Li, Ye; Zhang, Yuexin; Zhang, Qinyi; Li, Chunquan; Zhao, Yu; Huang, Xuemei; Xie, Liyuan; Zhang, Guorui; Fan, Shifan; Song, Chao] Univ South China, Sch Comp, Hengyang 421001, Hunan, Peoples R China.;[Li, Chunquan] Univ South China, Hunan Prov Maternal & Child Hlth Care Hosp, Hengyang Med Sch, Key Lab Birth Defect Res & Prevent,Natl Hlth Commi, Hengyang 421001, Hunan, Peoples R China.;[Li, Ye; Zhang, Yuexin; Li, Chunquan; Zhao, Yu; Huang, Xuemei; Xie, Liyuan; Zhang, Guorui; Fan, Shifan; Song, Chao] Univ South China, Affiliated Hosp 1, Cardiovasc Lab Big Data & Imaging ArtificialIntell, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.
通讯机构:
[Li, CQ ] U;Univ South China, Hengyang Med Sch, Affiliated Hosp 1, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Hengyang Med Sch, MOE Key Lab Rare Pediat Dis, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Sch Comp, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Hunan Prov Maternal & Child Hlth Care Hosp, Hengyang Med Sch, Key Lab Birth Defect Res & Prevent,Natl Hlth Commi, Hengyang 421001, Hunan, Peoples R China.
关键词:
genes;mice;candidate disease gene;inference;multiomics;oncogenes;enhancer of transcription;cell lines;transcription factor
摘要:
<jats:title>Abstract</jats:title>
<jats:p>Gene regulatory networks (GRNs) are interpretable graph models encompassing the regulatory interactions between transcription factors (TFs) and their downstream target genes. Making sense of the topology and dynamics of GRNs is fundamental to interpreting the mechanisms of disease etiology and translating corresponding findings into novel therapies. Recent advances in single-cell multi-omics techniques have prompted the computational inference of GRNs from single-cell transcriptomic and epigenomic data at an unprecedented resolution. Here, we present scGRN (https://bio.liclab.net/scGRN/), a comprehensive single-cell multi-omics gene regulatory network platform of human and mouse. The current version of scGRN catalogs 237051 cell type-specific GRNs (62 999692 TF–target gene pairs), covering 160 tissues/cell lines and 1324 single-cell samples. scGRN is the first resource documenting large-scale cell type-specific GRN information of diverse human and mouse conditions inferred from single-cell multi-omics data. We have implemented multiple online tools for effective GRN analysis, including differential TF–target network analysis, TF enrichment analysis, and pathway downstream analysis. We also provided details about TF binding to promoters, super-enhancers and typical enhancers of target genes in GRNs. Taken together, scGRN is an integrative and useful platform for searching, browsing, analyzing, visualizingand downloading GRNs of interest, enabling insight into the differences in regulatory mechanisms across diverse conditions.</jats:p>