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Novel PIKfyve/Tubulin Dual-target Inhibitor as a Promising Therapeutic Strategy for B-cell Acute Lymphoblastic Leukemia

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Current Medical Science 2024年第2期44卷 298-308页

作者： Zhen LU Qian LAI Zhi-feng li Meng-ya ZHONG Yue-long JIANG li-ying feng Jie ZHA Jing-wei YAO Yin li Xian-ming DENG Bing XU Department of Hematology The First Affiliated Hospital of Xiamen University and Institute of HematologySchool of MedicineXiamen UniversityXiamen361005China Key Laboratory of Xiamen for Diagnosis and Treatment of Hematological Malignancy Xiamen361005China Department of Oncology The First Affiliated Hospital of Jinan UniversityJinan UniversityGuangzhou510630China State Key Laboratory of Cellular Stress Biology Innovation Center for Cell Signaling NetworkSchool of Life SciencesXiamen UniversityXiamen361003China

Objective:In B-cell acute lymphoblastic leukemia(B-ALL),current intensive chemotherapies for adult patients fail to achieve durable responses in more than 50%of cases,underscoring the urgent need for new therapeutic regimens for this patient *** present study aimed to determine whether HZX-02-059,a novel dual-target inhibitor targeting both phosphatidylinositol-3-phosphate 5-kinase(PIKfyve)and tubulin,is lethal to B-ALL cells and is a potential therapeutic for B-ALL ***:Cell proliferation,vacuolization,apoptosis,cell cycle,and in-vivo tumor growth were *** addition,Genome-wide RNA-sequencing studies were conducted to elucidate the mechanisms of action underlying the anti-leukemia activity of HZX-02-059 in ***:HZX-02-059 was found to inhibit cell proliferation,induce vacuolization,promote apoptosis,block the cell cycle,and reduce in-vivo tumor *** of the p53 pathway and suppression of the phosphoinositide 3-kinase(PI3K)/AKT pathway and the downstream transcription factors c-Myc and NF-κB were responsible for these ***:Overall,these findings suggest that HZX-02-059 is a promising agent for the treatment of B-ALL patients resistant to conventional therapies.

关键词： B-cell acute lymphoblastic leukemia dual-target inhibitor NF-kB c-Myc PI3K/AKT p53

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超声引导下射频消融治疗子宫腺肌症的临床疗效分析

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中国现代药物应用 2024年第15期18卷 15-19页

作者：李凤英金乡县人民医院超声科 272200

目的探讨对子宫腺肌症采用超声引导下射频消融治疗的临床疗效。方法40例子宫腺肌症患者,以随机数字表法分为对照组和观察组,各20例。对照组患者采用药物保守治疗,观察组患者在药物保守治疗基础上采用超声引导下射频消融治疗。比较两组... 详细信息

目的探讨对子宫腺肌症采用超声引导下射频消融治疗的临床疗效。方法40例子宫腺肌症患者,以随机数字表法分为对照组和观察组,各20例。对照组患者采用药物保守治疗,观察组患者在药物保守治疗基础上采用超声引导下射频消融治疗。比较两组临床疗效,病灶与子宫体积、子宫内膜厚度,痛经、经量及贫血情况,复发风险[糖链抗原(CA)125及血管内皮生长因子(VEGF)水平]。结果观察组总有效率95.00%高于对照组的65.00%(P<0.05)。治疗3个月后,两组子宫与病灶体积较本组治疗前缩小,子宫内膜厚度较本组治疗前降低,且观察组子宫体积(92.57±14.28)cm^(3)、病灶体积(42.36±10.55)cm^(3)小于对照组的(132.48±16.31)、(64.47±12.31)cm^(3),子宫内膜厚度(5.72±0.74)mm低于对照组的(6.84±0.95)mm(P<0.05)。治疗3个月后,两组疼痛评分、月经失血图法评分较本组治疗前降低,血红蛋白水平较本组治疗前升高,且观察组疼痛评分(2.62±0.74)分、月经失血图法评分(69.51±10.26)分低于对照组的(3.28±0.95)、(85.77±14.41)分,血红蛋白水平(115.37±13.15)g/L高于对照组的(104.46±12.87)g/L(P<0.05)。治疗3个月后,两组CA125、VEGF水平均较本组治疗前降低,且观察组CA125(30.45±17.53)IU/ml、VEGF(117.25±12.83)ng/L低于对照组的(72.31±21.04)IU/ml、(139.61±15.25)ng/L(P<0.05)。结论对子宫腺肌症采用超声引导下射频消融治疗疗效确切,能改善痛经、月经紊乱及贫血情况,降低复发风险。

关键词：超声引导射频消融子宫腺肌症保守治疗痛经复发

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Well-dispersed Sb particles embedded on N-doped carbon nanofibers toward high-performance li-ion battery

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Rare Metals 2024年第7期43卷 2994-3006页

作者： ying li Yi-Han Zhao Lu-Lu Zhao Peng-Fei Wang ying Xie Ting-feng Yi School of Materials Science and Engineering Northeastern UniversityShenyang 110819China Key Laboratory of Dielectric and Electrolyte Functional Material Hebei Province School of Resources and MaterialsNortheastern University at QinhuangdaoQinhuangdao 066004China Key Laboratory of Functional Inorganic Material Chemistry Ministry of EducationSchool of Chemistry and Materials ScienceHeilongjiang UniversityHarbin 150080China

The alloy-type material Sb is widely used in the anode materials of lithium-ion batteries(liBs)due to its high theoretical specific ***,its serious volume expansion problem during alloying/dealloying of li~+limits its practical *** this work,C-Sb composite was constructed as anode material of liBs by electrospinning route for the first time,Sb was introduced into the polyacrylonitrile-based hard carbon and coal tar pitch-based soft carbon composite amorphous carbon fiber with a diameter of 300-600 nm,which realized high cycling *** C-Sb-2(the mass ratio of polyacrylonitrile to Sb source is 1:2)electrode displayed charge capacities of 1098.5,930.3,841.7,753.5,643.9 and 545.8 mAh·g^(-1)at 0.1,0.2,0.3,0.5,1 and 2 A·g^(-1),*** when the current density returned to 0.1 A·g^(-1),the charge capacity was 939.3 mAh·g^(-1),revealing good stability and *** introduction of Sb into the amorphous carbon improved its conductivity and addressed the volume expansion issue of high specific capacity Sb during charge/***-situ XRD analysis confirmed the high reversibility of the C-Sb-2 during charging and *** functional theory(DFT)calculations revealed the gradual enhancement of the interface interaction between Sb_(x)li_(y) and amorphous carbon(AMC)with increasing lithium content,contributing to the anchoring of alloy nanoparticles on the AMC surface and buffering the volume change of the ***,the gradual lithiation of Sb facilitated the electron transfer from Sb_(x)li_(y) to *** findings hold promise for designing lithium storage materials with exceptional performance,highlighting the potential of C-Sb composites as anode materials for efficient next-generation lithium storage.

关键词： li-ion battery Metallic Sb Carbon Electrospinning Cycling stability

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新型降糖药对初治失败的2型糖尿病治疗探讨

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中国城乡企业卫生 2024年第6期39卷 123-126页

作者：张艳丽李凤英天津港口医院内分泌科天津300456

目的探讨恩格列净联合利格列汀治疗初始治疗失败的2型糖尿病患者的疗效以及安全性。方法选取2018年9月—2020年8月天津港口医院收治的有治疗指征的2型糖尿病患者196例作为研究对象,应用随机数字表法分为对照组和观察组各98例。对照组采... 详细信息

目的探讨恩格列净联合利格列汀治疗初始治疗失败的2型糖尿病患者的疗效以及安全性。方法选取2018年9月—2020年8月天津港口医院收治的有治疗指征的2型糖尿病患者196例作为研究对象,应用随机数字表法分为对照组和观察组各98例。对照组采用二甲双胍联合瑞格列奈治疗,观察组在二甲双胍的基础上联合恩格列净及利格列汀。比较两组患者的空腹血糖(FBG)、餐后2 h血糖(2hPBG)、糖化血红蛋白(HbA1c)水平、临床疗效和不良反应发生发生率。结果观察组患者的FBG、2hPBG、HbA1c水平均低于对照组,差异均有统计学意义(P0.05)。结论初始治疗失败的2型糖尿病患者加用恩格列净联合利格列汀治疗,临床疗效明显,可有效降低患者血糖水平,不良反应少,安全性高。

关键词： 2型糖尿病利格列汀恩格列净

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Protective effect of inducible nitric oxide synthase inhibitor on pancreas transplantation in rats

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World Journal of Gastroenterology 2007年第45期13卷 6066-6071页

作者： Bai-feng li Yong-feng liu ying Cheng Ke-Zhong Zhang Tie-Min li Ning Zhao Department of Surgery and OrganTransplant Unit The First Affiliated Hospital China MedicalUniversity Shenyang 110001 Liaoning Province China

AIM: To investigate the effect of inducible nitric oxide synthase inhibitor, aminoguanidine, on pancreas transplantation in rats. METHODS: A model of pancreas transplantation was established in rats. Streptozotocin-induced diabetic male Wistar rats were randomly assigned to sham-operation control group (n= 6), transplant control group (n= 6), and aminoguanidine (AG) treatment group (n=18). In the AG group, aminoguanidine was added to intravascular infusion as the onset of reperfusion at the dose of 60 mg/kg, 80 mg/kg, 100 mg/kg body weight, respectively. Serum nitric oxide (NO) level, blood sugar and amylase activity were detected. Nitric oxide synthase (NOS) test kit was used to detect the pancreas cNOS and inducible NOS (iNOS) activity. Pancreas sections stained with HE and immunohistochemistry were evaluated under a light microscope. RESULTS: As compared with the transplant control group, the serum NO level and amylase activity decreased obviously and the evidence for pancreas injury was much less in the AG group. The AG (80 mg/kg body weight) group showed the most signifi cant difference in NO and amylase (NO: 66.0 ± 16.6 vs 192.3 ± 60.0, P < 0.01 and amylase: 1426 ± 177 vs 4477 ± 630, P < 0.01). The expression and activity of tissue iNOS, and blood sugar in the AG (80 mg/kg body weight) group were much lower than those in the transplant control group (iNOS: 2.01 ± 0.23 vs 26.59 ± 5.78, P < 0.01 and blood sugar: 14.2 ± 0.9 vs 16.8 ± 1.1, P < 0.01). CONCLUSION: Selective iNOS inhibitor, aminoguanidine as a free radical, has a protective effect on pancreas transplantation in rats by inhibiting NO and reducing its toxicity.

关键词： Pancreas Transplantation Inducible nitricoxide synthase Aminoguanidine Rat

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Gapless indica rice genome reveals synergistic contributions of active transposable elements and segmental duplications to rice genome evolution

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Molecular Plant 2021年第10期14卷 1745-1756页

作者： Kui li Wenkai Jiang Yuanyuan Hui Mengjuan Kong li-ying feng li-Zhi Gao Pengfu li Shan Lu State Key Laboratory of Pharmaceutical Biotechnology School of Life SciencesNanjing UniversityNanjing 210023China Novogene Bioinformatics Institute Building 301Zone A10 Jiuxianqiao North RoadChaoyang DistrictBeijing 100083China Institution of Genomics and Bioinformatics South China Agricultural UniversityGuangzhou 510642China Shenzhen Research Institute of Nanjing University Shenzhen 518000China

The ultimate goal of genome assembly is a high-accuracy gapless ***,we report a new assembly pipeline that is used to produce a gapless genome for the indica rice cultivar Minghui *** resulting 397.71-Mb final assembly is composed of 12 contigs with a contig N50 size of 31.93 *** chromosome is represented by a single contig and the genomic sequences of all chromosomes are *** evaluation of this gapless genome assembly showed that gene regions in our assembly have the highest completeness compared with the other 15 reported high-quality rice *** comparison with the japonica rice genome revealed that the gapless indica genome assembly contains more transposable elements(TEs)and segmental duplications(SDs),the latter of which produce many duplicated genes that can affect agronomic traits through dose effect or sub-/*** insertion of TEs can also affect the expression of duplicated genes,which may drive the evolution of these ***,we found the expansion of nucleotide-binding site with leucine-rich repeat disease-resistance genes and cis-zeatin-O-glucosyltransferase growth-related genes in SDs in the gapless indica genome assembly,suggesting that SDs contribute to the adaptive evolution of rice disease resistance and developmental ***,our findings suggest that active TEs and SDs synergistically contribute to rice genome evolution.

关键词： evolution gapless genome rice segmental duplications transposable elements

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Threshold Selection and Resource Allocation for Quantized Identification

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Journal of Systems Science & Complexity 2024年第1期37卷 204-229页

作者： WANG ying li Xin ZHAO Yanlong ZHANG Ji-feng Key Laboratory of Systems and Control Institute of Systems ScienceAcademy of Mathematics and Systems ScienceChinese Academy of SciencesBeijing 100190China School of Mathematical Sciences University of Chinese Academy of SciencesBeijing 100049China

This paper is concerned with the optimal threshold selection and resource allocation problems of quantized identification, whose aims are improving identification efficiency under limited resources. Firstly, the first-order asymptotically optimal quantized identification theory is extended to the weak persistent excitation condition. Secondly, the characteristics of time and space complexities are established based on the Cramér-Rao lower bound of quantized systems. On these basis, the optimal selection methods of fixed thresholds and adaptive thresholds are established under aperiodic signals, which answer how to achieve the best efficiency of quantized identification under the same time and space complexity. In addition, based on the principle of maximizing the identification efficiency under a given resource, the optimal resource allocation methods of quantized identification are given for the cases of fixed thresholds and adaptive thresholds, respectively, which show how to balance time and space complexity to realize the best identification efficiency of quantized identification.

关键词： Quantized output resource allocation system identification threshold selection.

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Synthesis of novel quaternary ammonium surfactants containing adamantane

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Chinese Chemical Letters 2012年第6期23卷 653-656页

作者： Jian Wei Guo Xing Zhong Hua Zhu li Juan feng ying De Cui Faculty of Chemical Engineering ＆ light Industry Guangdong University of Technology Guangzhou 510006 China

A series of novel quaternary ammonium surfactants containing adamantane were designed and synthesized from 1-adamanta- necarboxylic acid. The structures of target surfactants were confirmed by 1H NMR, elements analysis and FFIR. Surface properties of these surfactants were investigated. Due to the lipophilicity of adamantane, the critical micelle concentration （CMC） and C2o values of the synthesized quaternary ammonium surfactants are lower than that of conventional quaternary ammonium surfactants.

关键词： Adamantane Synthesis Quaternary ammonium surfactants 1-(Alkyldimethylammoniamethyl) adamantane bromide

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A dual-function selection system enables positive selection of multigene CRISPR mutants and negative selection of Cas9-free progeny in Arabidopsis

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aBIOTECH 2024年第2期5卷 140-150页

作者： feng-Zhu Wang ying Bao Zhenxiang li Xiangyu Xiong Jian-feng li State Key Laboratory of Biocontrol Guangdong Provincial Key Laboratory of Plant ResourcesSchool of Life SciencesSun Yat-sen UniversityGuangzhou 510275China

The CRISPR/Cas9 technology revolutionizes targeted gene knockout in diverse organisms including ***,screening edited alleles,particularly those with multiplex editing,from herbicide-or antibiotic-resistant transgenic plants and segregating out the Cas9 transgene represent two laborious *** solutions to facilitate these processes rely on different selection ***,by taking advantage of the opposite functions of a D-amino acid oxidase(DAO)in detoxifying D-serine and in metabolizing non-toxic D-valine to a cytotoxic product,we develop a DAO-based selection system that simultaneously enables the enrichment of multigene edited alleles and elimination of Cas9-containing progeny in Arabidopsis *** five DAOs tested in Escherichia coli,the one encoded by Trigonopsis variabilis(TvDAO)could confer slightly stronger D-serine resistance than other *** expression of TvDAO in Arabidopsis allowed a clear distinction between transgenic and nontransgenic plants in both D-serine-conditioned positive selection and D-valine-conditioned negative *** a proof of concept,we combined CRISPR-induced single-strand annealing repair of a dead TvDAO with D-serine-based positive selection to help identify transgenic plants with multiplex editing,where D-serine-resistant plants exhibited considerably higher co-editing frequencies at three endogenous target genes than those selected by ***,D-valine-based negative selection successfully removed Cas9 and TvDAO transgenes from the survival offspring carrying inherited ***,this work provides a novel strategy to ease CRISPR mutant identification and Cas9 transgene elimination using a single selection marker,which promises more efficient and simplified multiplex CRISPR editing in plants.

关键词： CRISPR Genome editing D-amino acid oxidase Cas9-free Selection marker

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NHC-derived carbon-centered luminescent radicals with shortwavelength emission via suppression of Kasha's rule

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Science China Chemistry 2024年第8期67卷 2679-2685页

作者： Can Chen Xin li Xinhua Ouyang ying-feng Han Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of the Ministry of Education Xi’an Key Laboratory of Functional Supramolecular Structure and MaterialsCollege of Chemistry and Materials ScienceNorthwest UniversityXi’an 710127China College of Material Engineering Fujian Agriculture and Forestry University Fuzhou 350108China

Luminescent organic radicals have garnered increasing attention owing to their versatile applications in sensing, imaging, and organic light-emitting diodes(OLEDs), attributed to their unique emission properties originating from the doublet spin ***, the natural narrow bandgap of organic free radicals typically limits their emission to the long-wavelength *** luminescent organic radicals with short-wavelength emission remains a significant challenge. Herein, a series of carbon-centered radicals with short-wavelength emission(383–476 nm) by combining N-heterocyclic carbenes with various polycyclic aromatic hydrocarbons(PAHs)(2-naphthyl, 2a~Ⅰ and 2b~Ⅰ;2-phenanthryl, 2a~Ⅱand 2b~Ⅱ;2-anthryl, 2a~Ⅲand 2b~Ⅲ;3-phenanthryl, 2a~Ⅳand 2b~Ⅳ). Theoretical calculations reveal that the introduction of PAHs significantly increases the ΔE_(D2-D1) in 2a^(Ⅰ–Ⅲ)and 2b^(Ⅰ–Ⅲ)compared to that in phenyl-derived radical congeners. Consequently, the internal transition from D2 to D1 is impeded, leading to a high yield of D2 emission and a suppressed Kasha's rule, thereby overcoming the limitations imposed by their narrow bandgap. For 2a~Ⅳ and 2b~Ⅳ, despite a moderately large ΔED2-D1value, the ΔED3-D1value exceeds 1 e V, indicating that their emission likely originates from the D3 state. Furthermore, we utilized 2a~Ⅲand 2b~Ⅲ as emissive materials in OLEDs,resulting in blue emissions with external quantum efficiencies of 7.5% and 6.5%, respectively.

关键词： N-heterocyclic carbenes luminescent organic molecules carbon-centered radicals short-wavelength emission

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