1.Research progress in the fungal bioluminescence pathway.
Lei LÜ ; Ke CHENG ; Zhitao XU ; Shijie AN ; Dang XU ; Hao DU
Chinese Journal of Biotechnology 2025;41(7):2545-2558
The fungal bioluminescence pathway (FBP) catalyzes the oxidation of endogenous caffeic acid to produce green bioluminescence through an enzymatic cascade. Genetic engineering of FBP into plants creates autoluminescent specimens that circumvent the substrate limitations of conventional reporter systems. These transgenic plants serve dual functions as aesthetic displays and versatile biosensing platforms, enabling applications in real-time gene expression monitoring, continuous environmental surveillance, and non-invasive bioimaging, offering novel opportunities for horticultural production, environmental conservation, and bioengineering applications. This review synthesizes current advances in plant FBP engineering and explores how machine learning approaches can optimize autoluminescent phenotypes, thereby accelerating innovation in agricultural biotechnology, environmental sensing, and synthetic biology applications.
Fungi/genetics*
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Plants, Genetically Modified/metabolism*
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Genetic Engineering
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Biosensing Techniques
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Luminescent Measurements
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Caffeic Acids/metabolism*
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Luminescence
2.Research advances in the association between diabetes mellitus and the formation and rupture of intracranial aneurysm
Maolu TAN ; Ke ZHANG ; Fajin LÜ
Journal of Chongqing Medical University 2025;50(8):1005-1010
Intracranial aneurysm(IA)is an abnormal tumor-like protrusion of intracranial blood vessels and has a relatively high in-cidence rate,and its rupture can lead to significantly poor prognosis.Diabetes mellitus(DM)is a common chronic disease character-ized by prolonged elevation of blood glucose level,which adversely affects the health of patients.Studies have confirmed the impact of long-term hyperglycemia on vascular health,and fragile blood vessels are an important prerequisite for the onset of aneurysms.There-fore,the patients with DM may have a higher incidence rate of aneurysms than those without DM.However,some studies have yielded conflicting results.Clarifying the mechanisms by which DM promotes the formation of IA and leads to subarachnoid hemorrhage after rupture may help to provide rational and individualized treatment for DM patients upon the identification of aneurysms and improve their prognosis.This article reviews the impact of DM on the formation and rupture of IA and related risk factors.
3.Feasibility of an in vitro phantom in high-resolution magnetic resonance imaging of endovaginal coil
Ke ZHANG ; Mingmei TANG ; Bin YU ; Hui LIU ; Yuanrui PAN ; Fajin LÜ
Journal of Chongqing Medical University 2025;50(9):1290-1296
Objective:To provide guidance on parameters for future endovaginal coil magnetic resonance imaging(MRI)in vivo,and to investigate the imaging potential of the endovaginal coil technique.Methods:The endovaginal coil was used to perform T2-weighted turbo spin echo sequence imaging on a phantom containing three spatial resolution modules,with variations in key imaging parameters.Signal-to-noise ratio(SNR),contrast-to-noise ratio(CNR),and contrast(C)were calculated for images under different imaging parameters,and image quality was assessed based on scores within specified intervals.Structural display scores were determined for the three resolution modules of the phantom,and the non-parametric tests were used for statistical comparison between groups.Results:Under the main imaging parameters of a slice thickness of 2 mm,a slice gap of 0.2 mm,4 times of excitation repetition,a matrix size of 384×384,an FOV of 52 mm×52 mm,a TE of 74 ms,a bandwidth of 180 Hz/Pixel,and an acceleration factor of 18,good image quality was obtained with an acquired spatial resolution of 0.14 mm×0.14 mm×2.00 mm and a reconstructed resolution of 0.07 mm×0.07 mm×2.00 mm,and all three resolution modules were clearly visualized with a clinically acceptable imaging time.There were signifi-cant differences between groups in the imaging quality scores of slice thickness,slice gap,number of excitations,FOV,and accelera-tion factor(P<0.05),while there were no significant differences in matrix,TE,and bandwidth between groups(P=0.521,0.502,and 0.566).There were significant differences in the structural display scores for all parameters between groups(P<0.05).Conclusion:The parameters obtained in this experiment can guide the future ap-plication of endovaginal coils in the human body,demonstrating the extremely high imaging potential of this technique,and endovaginal coil has the potential of identifying small lesions in future clinical practice.
4.Toxicokinetics of Chlorfenapyr and Its Metabolites in Rats
Wen-Yan LI ; Jin-Feng ZHAO ; Wei-Chen LIU ; Shi-Jing LÜ ; Jia-Xin ZHANG ; Xu-Dong ZHANG ; Zhi-Wen WEI ; Ke-Ming YUN ; Chao ZHANG
Journal of Forensic Medicine 2025;41(4):380-386
Objective To establish a chromatography-tandem mass spectrometry method for detecting chlorfenapyr and its metabolite tralopyril in blood,and to investigate the toxicokinetics in rats.Methods Chlorfenapyr(8 mg/kg)was administered orally to rats,and blood samples were collected from rats'canthus vein at 5 min,15 min,30 min,1 h,3 h,6 h,12 h,24 h and 48 h after administration.The blood samples were extracted using 100 μL of 5%formic acid solution and 400 μL of acetonitrile.Chlorfena-pyr was qualitatively and quantitatively detected by triple quadrupole gas chromatography-tandem mass spectrometry(GC-MS/MS)and tralopyril was detected by triple quadrupole liquid chromatography-tandem mass spectrometry(LC-MS/MS).The DAS 3.0 software was used to fit the toxicokinetic equa-tions and calculate the toxicokinetic parameters.Results Chlorfenapyr was detectable from 5 min to 24 h with a peak time of 1 h.Tralopyril was detectable from 15 min to 48 h with a peak time of 3 h.The toxicokinetic process of chlorfenapyr in rat blood conformed to a first-order absorption one-compartment open model,with the toxicokinetic equation described as C=e-0.265t-e-0.175t.Tralopyril con-formed to the first-order absorption three-compartment model,and the toxicokinetic equation was C=47 361.069e-2.209t-35 404.962e-1.486t+11 956.363e-0.512t.In the equations,C stands for the concentration of the target substance in the blood,e is the natural constant(≈2.718 28),and t stands for time.Conclu-sion This study optimized the detection method for chlorfenapyr and its metabolite tralopyril in blood.The toxicokinetic equations and parameters of chlorfenapyr and tralopyril can provide a reference for the estimation of oral intake time of chlorfenapyr.
5.Application of Histone Deacetylase Inhibitor in Acute Myeloid Leukemia
Dan-Dan CHEN ; Ke-Ning QIN ; Chun-Li LÜ ; Jian-Ye ZENG ; Xiao-Min WANG
Progress in Biochemistry and Biophysics 2024;51(6):1393-1405
Acute myeloid leukemia (AML) is a malignant clonal disease of hematopoietic stem cells, characterized by the proliferation of abnormal primordial cells of myeloid origin in bone marrow, blood and other tissues. At present, the standard induction therapy for AML mainly includes “3+7” standard treatment(anthracycline combined with cytarabine), allogeneic hematopoietic stem cell transplantation (Allo-HSCT) and targeted drug therapy. However, AML cells usually express high levels of P-glycoprotein, which mediates the efflux of chemotherapeutic drugs, which makes AML cells resistant to chemotherapy, resulting in many patients who are not sensitive to chemotherapy or relapse after complete remission. And some patients can not tolerate intensive therapy or lack of donors and can not use Allo-HSCT therapy. Therefore, it is of great clinical significance to find new drugs to improve the efficacy of AML patients. Epigenetic disorders play a key role in the pathogenesis of many diseases, especially cancer. Studies have shown that most AML patients have epigenetic regulatory gene mutations, such as DNMT3A, IDH and TET2, and these mutations are potentially reversible, which has become one of the therapeutic targets of AML. Histone deacetylase inhibitors (HDACi) can regulate the balance between histone acetylation and deacetylation, change the expression of proto-oncogenes or tumor suppressor genes that control cancer progression from epigenetics, and play an important role in many kinds of tumor therapy. At present, HDACi has shown the ability to induce differentiation, cell cycle arrest and apoptosis of AML cells. The mechanism may be mainly related to HDACi inducing chromatin conformation opening of tumor suppressor gene by inhibiting HDAC activity, promoting oncogene damage and preventing oncogene fusion protein from recruiting HDAC. Although the preclinical outcome of HDACi is promising, it is not as effective as the conventional therapy of AML. However, the combination strategy with various anticancer drugs is in clinical trials, showing significant anti-AML activity, improving efficacy through key targeting pathways in a typical synergistic or additive way, increasing AML sensitivity to chemotherapy, reducing tumor growth and metastasis potential, inhibiting cell mitotic activity, inducing cell apoptosis, regulating bone marrow microenvironment, which provides a good choice for the treatment of AML. Especially for those AML patients who are not suitable for intensive therapy and drug resistance to chemotherapy. This review introduces the relationship between HDAC and cancer; the classification of HDAC and its function in AML; the correlation between HDAC and AML; the clinical application of five types of HDACi; preclinical research results and clinical application progress of six kinds of HDACi in AML, such as Vrinota, Belinostat, Panobinostat, Valproic acid, Entinostat, and Chidamide, the mechanism of HDACi combined with other anticancer drugs in AML indicates that the current HDACi is mainly aimed at various subtypes of pan-HDAC inhibitors, with obvious side effects, such as fatigue, thrombocytopenia, nausea, vomiting, diarrhea. In recent years, the next generation of HDACi is mainly focused on the selectivity of analogues or isomers. Finding the best combination of HDACi and other drugs and the best timing of administration to balance the efficacy and adverse reactions is a major challenge in the treatment of AML, and the continued development of selective HDACi with less side effects and more accurate location is the key point for the development of this drug in the future. It is expected to provide reference for clinical treatment of AML.
6.Preliminary study of the transport and absorption mechanism of Astragalus polysaccharide-Ⅱ on M cells
Wan-wan LÜ ; Ke LI ; Shi-hong FENG ; Yu-wei WEN ; Xue-mei QIN ; Yu-guang DU ; Zhen-yu LI
Acta Pharmaceutica Sinica 2024;59(10):2820-2827
To explore the absorption mechanism of APS-Ⅱ
7.Discovery of the targets and lead compounds of traditional Chinese medicine based on the molecular trajectory of diabetes evolution
Yu ZHANG ; Jiang-lan LONG ; Ai-ting WANG ; Hao LÜ ; Ke-jun DENG ; Hao LIN ; Dan YAN
Acta Pharmaceutica Sinica 2024;59(8):2199-2204
Exploring the action targets (groups) of traditional Chinese medicine (TCM) is an important proposition to promote the innovation and development of TCM, but it has attracted a lot of attention as to whether it is related to the efficacy or the disease. Our team found that the metabolomic signature molecules in the development of diabetes mellitus (DM) were significantly associated with the clinical efficacy of Yuquan Pill through a large clinical sample study. Taking this as a clue, our team intends to expand the information on the omics features of DM development, and discover the key targets (groups) and their lead compounds for the hypoglycemic effect of Yuquan Pill. The project includes: ① Based on the retrospective clinical trials, using omics technology integrated with generative artificial intelligence, mining the characteristic information of proteome and microbiome, forming driving factors together with metabolome characteristic molecules, and characterizing the molecular trajectories of diabetes evolution and their interference by Yuquan Pill; ② Taking the evolving molecular trajectories as a link and pointer, using anthropomorphic modeling and molecular biology techniques such as chemical proteomics to discover the key targets (groups) of Yuquan Pill's hypoglycemic effect, with the prospective clinical samples for validation; ③ Evaluate the overall response of key targets (groups) using graph neural network technology, and search for drug-derived/endogenous lead compounds with proven clinical pathologies and clear mechanisms of action, so as to provide a new paradigm and technology for the discovery of complex active ingredient targets (groups) of TCM that are related to their clinical efficacy, as well as for the discovery of innovative medicines.
8.Clinical Value of CD44 mRNA and CD24 mRNA and Protein Expression Levels in Placental Tissue of Patients with Severe Preeclampsia
Lingling TENG ; Guangzhen MA ; Ke SHI ; Yingxin LÜ ; Jing XU
Journal of Modern Laboratory Medicine 2024;39(1):43-48
Objective To explore clinical value of the expression levels of cell surface transmembrane glycoprotein molecule 44(CD44)mRNA,cell surface transmembrane glycoprotein molecule 24(CD24)mRNA,and protein in the placenta of severe preeclampsia(SPE)patients.Methods The SPE patients who were delivered by cesarean section in the Second People's Hospital of Liaocheng from June 2019 to June 2022 were further divided into 45 patients in early onset SPE group(gestational age≤34 weeks)and 55 patients in late onset SPE group(gestational age>34 weeks)according to the different gestational age.The control group consisted of 100 normal cases in the same period.The expression of CD44 and CD24 in placenta of SPE patients was detected by fluorescent quantitative PCR and immunohistochemistry,Pearson method was used to analyze the difference of their expression levels and their correlation with the clinical characteristics of SPE disease,and multivariate logistic regression was used to analyze the influencing factors of SPE.Results Compared with the control group,the expression levels of CD44 mRNA(0.55±0.12 vs 1.02±0.33)and CD24 mRNA(0.68±0.19 vs 1.05±0.11)in SPE placental tissues decreased significantly,the differences were statistically significant(t=13.385,16.853,P<0.05).The immunohistochemical staining results showed that CD44 and CD24 were mostly negative or weakly positive in the SPE group placental tissue,while they were mostly positive in the control group,the positive rates of CD44 and CD24 in the SPE placental tissue were lower than those in the control group,and the differences were statistically significant(χ2=9.696,14.346,P<0.05).Compared to the early onset SPE group,the expression levels of CD44(0.65±0.17 vs 0.42±0.11)and CD24(0.77±0.23 vs 0.58±0.13)mRNA in placental tissue of late onset SPE were higher,and the differences were statistically significant(t=7.830,4.932,P<0.05).Compared with the control group,the BMI,systolic blood pressure,diastolic blood pressure,urinary protein,Cr,LDH and BUN were significantly increased in SPE group(t=5.360~30.241,all P<0.05).In SPE group,the gestational age was earlier,the MPV and ALB were lower,the newborn's birth length was shorter,and the body weight than control group,the differences were statistically great(t=3.232~11.109,all P<0.05).The expression of CD44 and CD24 in SPE placenta was positively correlated(r=0.698,P<0.05),the expression of CD44 in SPE placenta was positively correlated with CD24,gestational week of delivery,MPV and neonatal birth length(r=0.611,0.639,0.612,0.465,all P<0.05),and was negatively correlated with systolic blood pressure,urinary protein and LDH(r=-0.604,-0.569,-0.593,all P<0.05).The expression of CD24 was positively correlated with gestational age,MPV and newborn birth length(r=0.605,0.584,0.640,all P<0.05),and was negatively correlated with systolic blood pressure,urinary protein and LDH(r=-0.637,-0.593,-0.561,all P<0.05).The results of logistic regression analysis showed that MPV(95%CI:1.429~4.350),urinary protein(95%CI:1.529~2.709),and LDH(95%CI:1.425~3.932)were all independent risk factors for SPE(all P<0.05).High levels of CD44(95%CI:0.561~0.940)and CD24(95%CI:0.495~0.814)were independent protective factors for SPE(P<0.05).Conclusion The low expression levels of CD44 and CD24 in placenta of SPE patients are independent protective factors of SPE,which can provide direction for the follow-up treatment of SPE.
9.Rapid Screening of 34 Emerging Contaminants in Surface Water by UHPLC-Q-TOF-MS
Chen-Shan LÜ ; Yi-Xuan CAO ; Xiao-Xi MU ; Hai-Yan CUI ; Tao WANG ; Zhi-Wen WEI ; Ke-Ming YUN ; Meng HU
Journal of Forensic Medicine 2024;40(1):30-36
Objective To establish a rapid screening method for 34 emerging contaminants in surface water by ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry(UHPLC-Q-TOF-MS).Methods The pretreatment conditions of solid phase extraction(SPE)were op-timized by orthogonal experimental design and the surface water samples were concentrated and ex-tracted by Oasis? HLB and Oasis? MCX SPE columns in series.The extracts were separated by Kine-tex? EVO C18 column,with gradient elution of 0.1%formic acid aqueous solution and 0.1%formic acid methanol solution.Q-TOF-MS'fullscan'and'targeted MS/MS'modes were used to detect 34 emerging contaminants and to establish a database with 34 emerging contaminants precursor ion,prod-uct ion and retention times.Results The 34 emerging contaminants exhibited good linearity in the con-centration range respectively and the correlation coefficients(r)were higher than 0.97.The limit of de-tection was 0.2-10 ng/L and the recoveries were 81.2%-119.2%.The intra-day precision was 0.78%-18.70%.The method was applied to analyze multiple surface water samples and 6 emerging contaminants were detected,with a concentration range of 1.93-157.71 ng/L.Conclusion The method is simple and rapid for screening various emerging contaminants at the trace level in surface water.
10.Effects of Angelica Sinensis and Astragalus capsules on myocardial autophagy in rats with heart failure
Xue WU ; Xin-Fang LÜ ; Xiao-Dong ZHI ; Xin-Ke ZHAO ; Ying-Dong LI
The Chinese Journal of Clinical Pharmacology 2024;40(10):1453-1457
Objective To investigate whether Angelica Sinensis and Astragalus capsules(AAC)regulates myocardial autophagy in heart failure rats via the phosphatidylinositol 3 kinase(PI3K)/protein kinase(Akt)/mammalian target of sirolimus(mTOR)signaling pathway.Methods A rat model of heart failure was constructed by intraperitoneal 2.5 mg·kg-1 doxorubicin,and another 8 rats served as the control group.The modeling rats were randomly divided into model group,control group and experimental-L,-M,-H groups.Control group was given 30 mg·kg-1 3-methyladenine by intraperitoneal injection;experimental-L,-M,-H groups were given 150,300 and 450 mg·kg-1 AAC by gavage,respectively;blank and model groups were given the same quantity of sterile distilled water.Six groups were administered once daily for 6 weeks.The cardiac function was measured by ultrasound,and the expression levels of PI3K,Akt,mTOR,sequestosome 1(P62)and microtubule-associated light chain protein 3-Ⅱ/Ⅰ(LC3 Ⅱ/Ⅰ)in myocardial tissue were measured by Western blot.Results In the blank,model,control and experimental-H groups,the left ventricular ejection fraction values were(85.00±3.63)%,(56.75±4.83)%,(75.63±3.70)%and(72.75±4.23)%;the relative expression levels of PI3K were 1.00±0,0.28±0.05,0.64±0.08 and 0.74±0.16;phosphorylated Akt/Akt were 1.00±0,0.49±0.06,0.90±0.16 and 0.95±0.10;phosphorylated mTOR/mTOR values were 1.00±0,0.42±0.09,0.73±0.13 and 0.83±0.08;the relative expression levels of P62 proteins were 1.00±0,0.24±0.12,0.57±0.09 and 0.96±0.10;the relative expression levels of LC3 Ⅱ/Ⅰ proteins were 1.00±0,4.31±0.75,2.20±0.76 and 1.59±0.24,respectively.Compared to the model group,statistical significant were identified in the experimental-H and control groups(all P<0.05).Conclusion AAC can regulate PI3K/Akt/mTOR pathway,inhibit myocardial autophagy and improve cardiac function in rats with heart failure.

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