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.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.
3.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.
4.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.
5.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
6.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.
7.Diagnostic application of polysomnography combined with arterial spin labeling perfusion magnetic resonance imaging in insomnia
Xiaohong NI ; Yanwen LÜ ; Hongyan KE ; Yu TIAN ; Yuangao LIAO
Chinese Journal of Medical Physics 2024;41(8):1010-1014
Objective To explore the application of polysomnography combined with arterial spin labeling(ASL)perfusion magnetic resonance imaging in the diagnosis of insomnia.Methods Forty-two insomnia patients admitted to Department of Neurology were included as insomnia group,while 41 healthy subjects during the same period were included as control group.The two groups were assessed using sleep habits questionnaire,hospital anxiety and depression scale,polysomnography,and ASL perfusion magnetic resonance imaging.Results Compared with control group,insomnia group took significantly more time to fall asleep(P<0.05),and has shorter sleep duration(P<0.05).The differences in the levels of anxiety and depression between two groups were trivial.The total sleep time,rapid eye movement sleep duration,and non-rapid eye movement sleep stage S2-S4were shorter,while the sleep latency and non-rapid eye movement sleep stage S1were longer in insomnia group as compared with control group(all P<0.05).In insomnia group,perfusion was increased in bilateral prefrontal lobes,right temporal lobe,left parietal lobe,right thalamus,and pons(P<0.05),but decreased in bilateral insula and bilateral basal ganglia(P<0.05).Conclusion The combination of polysomnography and ASL perfusion magnetic resonance imaging enables precise quantification of sleep condition.
8.A single-center study on the safety and effectiveness of a novel non-implant interatrial shunt device
San-Shuai CHANG ; Xin-Min LIU ; Zheng-Ming JIANG ; Yu-Tong KE ; Qian ZHANG ; Qiang LÜ ; Xin DU ; Jian-Zeng DONG ; Guang-Yuan SONG
Chinese Journal of Interventional Cardiology 2024;32(8):425-433
Objective To preliminarily evaluate the safety and effectiveness of a novel non-implantable atrial shunt device based on radiofrequency ablation for the treatment of chronic heart failure(CHF).Methods This was a prospective single-arm study.From January 2023 to December 2023,five eligible CHF patients were consecutively enrolled at Beijing Anzhen Hospital,Capital Medical University,and underwent inter-atrial shunt using Shenzhen Betterway atrial shunt device.Pulmonary capillary wedge pressure(PCWP),right atrial pressure(RAP),pulmonary artery pressure(PAP),total pulmonary resistance(TPR),pulmonary vascular resistance(PVR),and pulmonary/systemic blood flow ratio(Qp/Qs)were measured using right heart catheterization before and immediately after procedure.Patients were followed up for 90 days,and echocardiography,right heart catheterization,and cardiac functional indicators were evaluated.The primary endpoint was procedural success.Secondary endpoints included clinical success,echocardiographic changes,6-minute walk distance(6MWD)changes,New York Heart Association(NYHA)class changes,Kansas city cardiomyopathy questionnaire(KCCQ)score changes,and amino-terminal probrain natriuretic peptide(NT-proBNP)level changes at 90 days.The safety endpoint was major cardiovascular and cerebrovascular adverse events and device-related adverse events.Results All five patients successfully achieved left-to-right atrial shunt.Compared with baseline,PCWP decreased significantly immediately after procedure in all five patients,with a procedural success rate of 100%.There were no significant changes in RAP,PAP,TPR,and PVR before and immediately after procedure.After 90 days follow-up,four patients had persistent left-to-right atrial shunt,and PCWP was significantly lower than baseline,with a clinical success rate of 80%.Compared with baseline,LVEF increased,left ventricular end-diastolic diameter decreased,and tricuspid annular plane systolic excursion and right ventricular fractional area change were not impaired in all five patients at 90 days.KCCQ scores and 6MWT improved,NT-proBNP decreased,and NYHA class did not change significantly.There were no deaths,rehospitalizations for heart failure,stroke-related adverse events,or device-related adverse events during the follow-up.Conclusions The novel non-implantable atrial shunt catheter can safely and effectively improve hemodynamic,echocardiographic,and cardiac functional indicators in patients with heart failure.However,larger-scale clinical studies are still needed to validate its long-term clinical effectiveness.
9.Optimisation of CUBIC tissue clearing technology based on perfusion methods
Chuan-Hui GONG ; Jia-Yi QIU ; Ke-Xin YIN ; Ji-Ru ZHANG ; Cheng HE ; Ye YUAN ; Guang-Ming LÜ
Acta Anatomica Sinica 2024;55(3):363-370
Objective In order to shorten the transparency time of clear,unobstructed brain imaging cocktails and computational analysis(CUBIC),improve the transparency efficiency,and explore the possibility of applying hydrophilic tissue transparency technique,this study was conducted to optimize the perfusion of CUBIC technique and compare it with four hydrophilic tissue clearing method in terms of tissue transparency effect,transparency time,area change,volume change and adeno-associated virus(AAV)fluorescence retention.Methods Brain,liver,spleen and kidney of 6 adult Institute of Cancer Research(ICR)mice were subjected to clearing treatment by SeeDB,FRUIT,ScaleS and CUBIC method,respectively.The area and gray value of the samples were measured by Image J 1.8.0,and the volume before and after transparency was measured by drainage method to compare the transparency effect,time and size deformation of each group.Perfusion optimization of the CUBIC was performed by improving the perfusion rate with the optimal perfusion dose,each group of the experimental sample size was 6.Fluorescence preservation by different techniques was evaluated by injecting AAV in the motor cortex of 16 adult mice and taking the cervical spinal segments for transparency treatment after four weeks,and the fluorescence photographs were measured by Image J 1.8.0 to measure the mean fluorescent intensity.Results The optimal perfusion rate and dose of CUBIC was 15 ml/min and 200 ml respectively.For transparency ability and speed,the perfusion CUBIC had the lowest mean gray value and took the shortest time,while CUBIC consumed the longest time,and SeeDB,FRUIT,and ScaleS did not show good transparency ability.In terms of area and volume changes,several techniques showed different degrees of expansion after transparency of tissues or organs.In terms of fluorescence retention,perfusion CUBIC showed the best retention of green fluorescent protein(GFP)fluorescence signal,followed by CUBIC,ScaleS,FRUIT,and SeeDB.Conclusion Perfusion CUBIC technique shows the best tissue transparency,the shortest transparency time,and the most AAV fluorescence retention compared with other techniques.
10.EDAG protects hematopoietic stem cells from damage induced by chronic inflammation
Siyu LI ; Ke ZHAO ; Yunqiang WU ; Zhichun LÜ ; Huiying SUN ; Xiongwei ZHAO ; Yang XUE ; Huiying GAO ; Shensi XIANG ; Changyan LI
Military Medical Sciences 2024;48(8):594-600
Objective To investigate the effect of erythroid differentiation associated gene(EDAG)on hematopoietic stem/progenitor cells(HSPCs)under chronic inflammation.Methods In this study,EDAG-/-and wild type(WT)mice were divided into the experiment group and control group.An infectious chronic inflammation model was established via multiple intraperitoneal injections of Listeria monocytogenes(LM),while a sterile chronic inflammation model was generated via multiple intraperitoneal injections of polyinosinic-polycytidylic acid[Poly(I∶C)].The effect of EDAG on HSPCs was explored under chronic inflammation conditions.Results In the LM repeated infection model,EDAG deletion led to a decrease in HSPCs and long-term hematopoietic stem cells(LT-HSCs)in mice as well as a significant bias towards myeloid differentiation in peripheral blood.Similarly,EDAG knockout also resulted in reduced numbers of HSPCs and decreased colony-forming ability in aseptic chronic inflammation models.Conclusion EDAG deficiency accelerates HSPC depletion in young mice under chronic inflammation,indicating strong protection of EDAG against HSPC damage induced by chronic inflammation.

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