1.Lysosomes as Regulators of Cancer Stemness and Drug Resistance
Fa-Xiao ZHOU ; Di-Ping YU ; Si-Qi TAN ; Hong-Yu DUAN ; Xiao-Ming WU
Progress in Biochemistry and Biophysics 2026;53(4):951-967
Cancer stem cells (CSCs) represent a distinct subpopulation of cells characterized by self-renewal capacity, differentiation potential, and critical roles in driving tumor progression, therapeutic resistance, recurrence, and maintenance of the tumor microenvironment. Targeting CSCs has emerged as a pivotal direction in cancer research, offering novel strategies to overcome drug resistance and prevent metastasis and relapse. Lysosomes, traditionally recognized as central organelles for intracellular degradation and recycling, are indispensable for cellular homeostasis. Dysregulation of lysosomal function is intimately linked to various diseases, including cancer. In tumors, aberrant lysosomal activity can promote malignant progression through mechanisms such as altering metabolic pathways, enhancing lysosomal exocytosis, modulating drug resistance, and interfering with autophagy-lysosomal pathways. Recent studies have underscored the involvement of lysosomes in regulating CSC properties. This review synthesizes findings on lysosomal regulation of CSCs through the following aspects. (1) Lysosomes exert complex and critical bidirectional control over CSC stemness maintenance through three degradation pathways that are dependent on their degradative function. (i) The lysophagy pathway. This pathway exhibits dual roles. Activation can sustain CSC functions; for instance, in glioblastoma, hypoxia upregulates Gal-8 via the STAT3/HIF1α signaling axis to induce autophagy, supporting stem cell survival. In head and neck squamous cell carcinoma, degradation of GSK3β activates the Wnt pathway, enhancing stemness. Conversely, this pathway can suppress stemness by degrading stemness-related proteins such as BMI-1 and OCT4A, thereby impairing CSC self-renewal capacity. (ii) Mitophagy pathway. In non-small cell lung cancer stem cells, mitophagy-related mechanisms, such as the accumulation of mitochondrial DNA (mtDNA) activating the TLR9-Notch1-AMPK signaling axis, have been shown to promote CSC proliferation. (iii) Autophagosome-dependent lysosomal degradation pathway. This pathway directly regulates stemness-related proteins in a bidirectional manner. Enhanced degradative function can promote CSC properties, exemplified by the degradation of NUMB to activate Notch signaling. Conversely, attenuated degradative function can also enhance stemness by stabilizing oncoproteins (e.g., protecting Frizzled-1 from degradation to sustain Wnt signaling) or preventing the degradation of tumor suppressors (e.g., inhibiting Notch degradation). (2) Constituent proteins of lysosomes, including membrane proteins and luminal acid hydrolases, participate in regulating CSC stemness. Regarding membrane proteins, LAMP2A facilitates chaperone-mediated autophagy to maintain stemness in glioblastoma and ovarian cancer. V-ATPase, by maintaining an acidic luminal environment, promotes proliferation and drug resistance in glioma stem cells. Among hydrolases, cathepsins B and L are highly expressed in pancreatic and ovarian cancers and correlate with poor prognosis. Furthermore, targeting lysosomes to induce lysosomal membrane permeabilization (LMP) triggers lysosome-mediated cell death, presenting a potential therapeutic strategy for eradicating CSCs.(3) The acidic luminal environment, single-membrane structure, and the presence of transmembrane transporters (e.g., ABCA3) enable lysosomes to passively trap or actively uptake and sequester chemotherapeutic drugs. Subsequent drug extrusion via exocytosis confers drug resistance. In CSCs, this lysosome-mediated drug sequestration, often cooperating with autophagy, establishes multimodal drug resistance. Therefore, targeting lysosomal function represents a potential strategy to overcome therapy resistance. The central role of lysosomes in regulating CSC stemness and resistance positions them as highly promising therapeutic targets. Strategies aimed at disrupting lysosomal function to selectively eliminate CSCs include: inhibiting the lysosome-autophagy system using agents like IITZ or lovastatin; inducing lysosomal membrane permeabilization (LMP) with compounds such as hexamethylene amiloride to compromise membrane stability; and disrupting the acidic luminal environment using drugs like siramesine or the K/H transport compound 2. In conclusion, lysosomes critically regulate CSC stemness maintenance and drug resistance through degradative pathways, membrane protein functions, luminal hydrolase activities, and drug sequestration mechanisms. This redefines the lysosome from a traditional “waste disposal unit” to a “signal integration center” in CSCs. The duality and context-dependency of lysosomal function in CSCs offer novel insights into the heterogeneity observed across different tumors. Targeting lysosomal vulnerabilities—such as inducing LMP, disrupting acidity, or blocking autophagic flux—provides a strategy to bypass canonical CSC resistance mechanisms and directly trigger cell death. This establishes the lysosome as a key target to overcome CSC-mediated therapy resistance, paving the way for developing diverse candidate drugs and innovative combination therapies in oncology.
2.Clinical Advantages of Traditional Chinese Medicine in Treatment of Childhood Simple Obesity: Insights from Expert Consensus
Qi ZHANG ; Yingke LIU ; Xiaoxiao ZHANG ; Guichen NI ; Heyin XIAO ; Junhong WANG ; Liqun WU ; Zhanfeng YAN ; Kundi WANG ; Jiajia CHEN ; Hong ZHENG ; Xinying GAO ; Liya WEI ; Qiang HE ; Qian ZHAO ; Huimin SU ; Zhaolan LIU ; Dafeng LONG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(6):238-245
Childhood simple obesity has become a significant public health issue in China. Modern medicine primarily relies on lifestyle interventions and often suffers from poor long-term compliance, while pharmacological options are limited and associated with potential adverse effects. Traditional Chinese Medicine (TCM) has a long history in the prevention and management of this condition, demonstrating eight distinct advantages, including systematic theoretical foundation, diversified therapeutic approaches, definite therapeutic efficacy, high safety profile, good patient compliance, comprehensive intervention strategies, emphasis on prevention, and stepwise treatment protocols. Additionally, TCM is characterized by six distinctive features: the use of natural medicinal substances, non-invasive external therapies, integration of medicinal dietetics, simple exercise regimens, precise syndrome differentiation, and diverse dosage forms. By combining internal and external treatments, TCM facilitates individualized regimen adjustment and holistic regulation, demonstrating remarkable effects in improving obesity-related metabolic indicators, regulating constitutional imbalance, and promoting healthy behaviors. However, challenges remain, such as inconsistent operational standards, insufficient high-quality clinical evidence, and a gap between basic research and clinical application. Future efforts should focus on accelerating the standardization of TCM diagnosis and treatment, conducting multicenter randomized controlled trials, and fostering interdisciplinary integration, so as to enhance the scientific validity and international recognition of TCM in the prevention and treatment of childhood obesity.
3.Differences in deltamethrin resistance and kdr gene mutation in Culex tritaeniorhynchus population in and outside the Yellow Sea wetland
Xiao-er ZHANG ; Zhi-ming WU ; Ye TIAN ; Qian CUI ; Yu-qian JI ; Huan WANG ; Shu-juan YANG ; Yi-chao ZHAO ; Yu WANG ; Hua-yu YIN ; Yu DING ; Guo-jin YAN ; Min-sen ZHAO ; Shou-gang ZHANG ; Bing-dong SONG ; Hong-na CHEN ; Jian GAO ; Wei-fang YANG ; Yu-fu ZHANG ; Hui LIU ; Hong-liang CHU
Acta Parasitologica et Medica Entomologica Sinica 2026;33(2):101-107
Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.
4.The first record of Anopheles messeae (Diptera: Culicidae) parasitized by water mites in China
Xue-ru CHEN ; Wen-zhen YAO ; Yu-hao LI ; Gui-chang LI ; Tao MENG ; Qun-ling FENG ; Xin-hui LIU ; Li-hong QIAO ; Xiang-ting WU ; Xue-feng ZHANG ; Cheng-lin LI ; Xue-cheng DONG ; Da-wei WANG ; Xiao-yan SI ; Yu-hong GUO
Acta Parasitologica et Medica Entomologica Sinica 2026;33(1):53-57
Objective This study reports on the obligatory parasitism of water mites Arrenurus sp. on Anopheles messeae at the Manzhouli Port, Inner Mongolia, China. Methods Duing July 2024, a survey on the mosquito diversity was conducted at the Manzhouli Port. Captured mosquitoes and their ectoparasites were identified to species level. Results A total of 1840 adult mosquitoes were collected, representing species from three genera: Culex(Cx. modestus, Cx. pipiens pallens), Aedes(Ae. dorsalis, Ae. flavidorsalis, Ae. flavescens), and Anopheles (An. messeae). Among all the mosqutioes specimens,3 out of 150 captured An. messeae were found to carry ectoparasitic mites, with number of 2,4,27 mites separately. Morphological and molecular identification reached the same result as water mites(Hydrachnidiae, Hydracrina). COI gene sequence showed 94% similarity with the closest species Arrenurus truncatellus. Conlusions Literature review suggests water mites are host-specific parasitism of mosquito species and herein with the first record of Arrenurus sp. parasiting on An. Messeae in the most high-latitude region globally.
5.Dual-modal Magnetic Resonance Imaging Contrast Agents Based on Polymetallic Nanoclusters for Targeted Diagnosis of Prostate Cancer
Qing-Dong LI ; Peng WANG ; Jian-Min XIAO ; Wen-Juan GAO ; Zhen-Hong XIA ; Gui-Long ZHANG ; Zheng-Yan WU
Chinese Journal of Analytical Chemistry 2025;53(4):602-611
Fe/Mn/Gd polymetallic nanooxide(FMGN)were prepared by one-step solvent thermal reaction by using Fe(acac)3,Mn(acac)2 and Gd(acac)3 as reaction precursors.Next,hyaluronic acid(HA)was used to modify FMGN to fabricate tumor-targeting T 1-T 2 dual-mode magnetic resonance imaging(MRI)contrast agent(HA-FMGN)for accurate diagnosis of prostate cancer.The structure and morphology of FMGN were observed by transmission electron microscope(TEM).It was found that FMGN exhibited a uniform nanocluster spherical structure when the feeding ratio of iron acetylacetonate,manganese acetylacetonate,and gadolinium acetylacetonate was 3:2:1.X-ray diffraction(XRD)analysis showed that FMGN had a typical inverse spinel structure of Mn doped Fe 3O 4,with Gd existing in the form of amorphous gadolinium oxide.The longitudinal relaxivity(r 1)and transverse relaxivity(r 2)of FMGN were 13.395 and 428.535 L/(mmol·s),respectively,measured by 0.5 T MRI analyzer,which proved that FMGN had excellent T 1-T 2 dual-mode MRI contrast capability.The cytotoxicity and hemolysis test found that HA-FMGN didn't damage red cells and induce toxicity for normal cells,indicating that HA-FMGN had excellent cell biocompatibility.The internalization efficacy of HA-FMGN was observed by CLSM,and the results showed that HA-FMGN possessed excellent prostate tumor-targeting ability.In vivo MRI experiment showed that HA-FMGN significantly enhanced T 1 and T 2 weighted MRI signal to noise ratio(SNR)of prostate tumor,which promoted the accurate diagnosis of orthotopic prostate cancer.
6.Analyzing Promotion Effect of Rare Earth Species Located in Ce-HY on Polyethylene Upgrading
Xue-Ting WU ; Jing XU ; Xiao-Wei MU ; Long TIAN ; Xiao WANG ; Shu-Yan SONG ; Hong-Jie ZHANG
Chinese Journal of Analytical Chemistry 2025;53(5):794-803
The continuous accumulation of plastic waste such as polyethylene in the environment has caused serious environmental pollution issues.Considering the high similarity in the molecular structure of petroleum and polyolefin,it is feasible to apply rare earth-zeolite catalysts in polyolefin plastic upcycling,which is commonly used in fluid catalytic cracking(FCC)in the field of petroleum refining.In this study,Ce-modified HY(Ce-HY)zeolites were synthesized and characterized by a series of analytical methods,such as high-angle annular dark-field scanning transmission electron microscopy(HAADF-STEM),Fourier infrared spectroscopy(FT-IR),X-ray photoelectron spectroscopy(XPS),etc.When introducing 5% Ce species into HY zeolites,the 5Ce-HY showed excellent catalytic performance in the catalytic cracking of low-density polyethylene(LDPE),which achieved 98.4% LDPE conversion with 91.5% selectivity of gaseous alkanes at 300℃,and 75.4% of them were isoparaffins.In addition,the effect of the location of rare earth species in Y zeolites on the catalytic performance was explored by fine X-ray diffraction(XRD)in the range of 11°-13°and in situ-Raman analyses.The Ce species located in the supercage of Y zeolites were more important,which enhanced the adsorption capacity and accessibility of substrate molecules,thus facilitating the entire catalytic cracking process.This method could be used to detect the location of rare earth elements in Y zeolites to understand the mechanism of rare earth catalysis.
7.Malonylation Proteomics Study of Hepatocellular Carcinoma Tissues Using Liquid Chromatography-Mass Spectrometry
Meng ZHANG ; Xiao LONG ; Yan-Nan WU ; Hao SI ; Hong-Xia WANG
Chinese Journal of Analytical Chemistry 2025;53(9):1546-1554
Malonylation is an important post-translational modification of proteins.In this work,a comprehensive malonylation proteomics study on hepatocellular carcinoma(HCC)tumorous and non-tumorous tissues using antibody enrichment combined with high performance liquid chromatography-mass spectrometry for discovery of early diagnostic biomarkers or potential new drug targets of HCC was performed.A total of 1299 malonylated peptides containing 1064 malonylated sites were identified from HCC tissues,corresponding to 511 malonylated proteins.Quantitative results showed that 56 and 80 malonylated proteins were up-regulated and down-regulated in HCC tissues,including 60 and 101 malonylated sites,respectively.Kyoto encyclopedia of genes and genomes(KEGG)pathway analysis showed that these differentially modified proteins were involved in various important pathways such as metabolic pathways,fatty acid degradation,and glycolysis/gluconeogenesis.As a key enzyme in glycolysis/gluconeogenesis,phosphoenolpyruvate carboxykinase 1(PCK1)was malonylated at lysine 244(K244)and the malonylation was only detected in HCC tumorous tissues.More importantly,the K244 site served as a binding site for Mn2+and highly conserved across different species.Therefore,it could speculate that the malonylation of K244 would affect its activity and played a role in liver cancer by affecting its binding with Mn2+,which requied further verification through site mutation experiments.Western blot analysis by malonylation pan antibody showed that the malonylation level reduced markedly in HCC tumorous tissues compared with adjacent non-tumorous tissues,which was consistent with mass spectrometry data.In addition,the proliferation and invasion of PLC/PRF/5 cell was significantly inhibited and protein malonylation level was increased obviously when treated with sodium malonate.All the evidence indicated that protein malonylation played an important role in HCC pathogenesis,and its molecular mechanism deserved further investigation.Furthermore,the 136 differentially malonylated proteins provided rich source of candidate targets for further research on HCC pathogenesis.
8.Study on development of teachers'teaching ability from perspective of core competitiveness of medical colleges
Hong YANG ; Xiao HAN ; Guiqing LI ; Boshao DENG ; Jian XIONG ; Yuzhang WU ; Jian CHEN
Chinese Journal of Immunology 2025;41(2):439-443
Core competitiveness of medical colleges and universities refers to their unique advantages and abilities in teaching,research and serving society compared to other colleges.As an important part of core competitiveness of medical colleges,teachers'teaching ability directly affects students'learning effect and quality training,and also relates to overall promotion process of core com-petitiveness of medical colleges.From perspective of core competitiveness of medical colleges,this paper analyzes and combs develop-ment of teachers'teaching ability from theoretical definition of core competitiveness of medical colleges,finds bottleneck of improving teachers'teaching ability,and puts forward suggestions for improving teachers'teaching ability in medical colleges,so as to improve teachers'teaching ability in medical colleges.
9.Advancements and applications in radiopharmaceutical therapy.
Shiya WANG ; Mingyi CAO ; Yifei CHEN ; Jingjing LIN ; Jiahao LI ; Xinyu WU ; Zhiyue DAI ; Yuhan PAN ; Xiao LIU ; Xian LIU ; Liang-Ting LIN ; Jianbing WU ; Ji LIU ; Qifeng ZHONG ; Zhenwei YUAN
Chinese Journal of Natural Medicines (English Ed.) 2025;23(6):641-657
Radiopharmaceuticals operate by combining radionuclides with carriers. The radiation energy emitted by radionuclides is utilized to selectively irradiate diseased tissues while minimizing damage to healthy tissues. In comparison to external beam radiation therapy, radionuclide drugs demonstrate research potential due to their biological targeting capabilities and reduced normal tissue toxicity. This article reviews the applications and research progress of radiopharmaceuticals in cancer treatment. Several key radionuclides are examined, including 223Ra, 90Y, Lutetium-177 (177Lu), 212Pb, and Actinium-225 (225Ac). It also explores the current development trends of radiopharmaceuticals, encompassing the introduction of novel radionuclides, advancements in imaging technologies, integrated diagnosis and treatment approaches, and equipment-medication combinations. We review the progress in the development of new treatments, such as neutron capture therapy, proton therapy, and heavy ion therapy. Furthermore, we examine the challenges and breakthroughs associated with the clinical translation of radiopharmaceuticals and provide recommendations for the research and development of novel radionuclide drugs.
Humans
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Radiopharmaceuticals/therapeutic use*
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Neoplasms/radiotherapy*
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Radioisotopes/therapeutic use*
;
Animals
10.Laboratory Diagnosis and Molecular Epidemiological Characterization of the First Imported Case of Lassa Fever in China.
Yu Liang FENG ; Wei LI ; Ming Feng JIANG ; Hong Rong ZHONG ; Wei WU ; Lyu Bo TIAN ; Guo CHEN ; Zhen Hua CHEN ; Can LUO ; Rong Mei YUAN ; Xing Yu ZHOU ; Jian Dong LI ; Xiao Rong YANG ; Ming PAN
Biomedical and Environmental Sciences 2025;38(3):279-289
OBJECTIVE:
This study reports the first imported case of Lassa fever (LF) in China. Laboratory detection and molecular epidemiological analysis of the Lassa virus (LASV) from this case offer valuable insights for the prevention and control of LF.
METHODS:
Samples of cerebrospinal fluid (CSF), blood, urine, saliva, and environmental materials were collected from the patient and their close contacts for LASV nucleotide detection. Whole-genome sequencing was performed on positive samples to analyze the genetic characteristics of the virus.
RESULTS:
LASV was detected in the patient's CSF, blood, and urine, while all samples from close contacts and the environment tested negative. The virus belongs to the lineage IV strain and shares the highest homology with strains from Sierra Leone. The variability in the glycoprotein complex (GPC) among different strains ranged from 3.9% to 15.1%, higher than previously reported for the seven known lineages. Amino acid mutation analysis revealed multiple mutations within the GPC immunogenic epitopes, increasing strain diversity and potentially impacting immune response.
CONCLUSION
The case was confirmed through nucleotide detection, with no evidence of secondary transmission or viral spread. The LASV strain identified belongs to lineage IV, with broader GPC variability than previously reported. Mutations in the immune-related sites of GPC may affect immune responses, necessitating heightened vigilance regarding the virus.
Humans
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China/epidemiology*
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Genome, Viral
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Lassa Fever/virology*
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Lassa virus/classification*
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Molecular Epidemiology
;
Phylogeny


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