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.

As an indispensable trace element in the human body,copper plays an important role in various physiological and biochemical reactions.The dyshomeostasis of copper leads to the disorder of copper metabolism and the occurrence of related diseases.Cuproptosis,a newly proposed regulatory cell death mode,is different from the known apoptosis,pyroptosis,necroptosis,and ferroptosis.Recent studies have found that the dyshomeostasis of copper has been observed in a variety of cancers.Therefore,targeting copper for disease treatment may become a new strategy and a new idea.This article systematically summarizes the fundamental properties of copper,copper dyshomeostasis-related diseases (Menkes syndrome,Wilson's disease,and cancer) and their treatment,and reviews the research progress in cuproptosis.
Humans ; Copper/metabolism* ; Homeostasis ; Neoplasms/metabolism* ; Hepatolenticular Degeneration/metabolism* ; Menkes Kinky Hair Syndrome/metabolism*

Objective To explore the synergistic therapeutic effect of sodium butyrate and Sishen pill on mice with diarrhea with kidney-yang deficiency syndrome,and provide experimental evidence for the contemporary application of classical prescriptions.Methods The diarrhea with kidney-yang deficiency syndrome mouse model was construc-ted by gavage of adenine combined with Folium sennae.Mice were given 100％Sishen pill decoction,50 mg/kg so-dium butyrate+75％Sishen pill decoction,100 mg/kg sodium butyrate+50％Sishen pill decoction,200 mg/kg so-dium butyrate+25％Sishen pill decoction,and 300 mg/mL sodium butyrate decoction by intragastric administra-tion,respectively.General condition,food and water intake,anal temperature,body weight,fecal water content,organ index,intestinal microbiota,and enzyme activity of the mice were compared.Results After treatment,the general condition,food and water intake,anal temperature,and fecal water content of the mice gradually recovered.The body weight of mice from the natural recovery group,the 200 mg/kg sodium butyrate+25％ Sishen pill group,and the 50 mg/kg sodium butyrate+75％ Sishen pill group still showed statistical differences from the normal group(P＜0.05).The body weight of mice from the 100 mg/kg sodium butyrate+50％ Sishen pill group(34.23±4.93)g increased,close to the body weight of mice from the normal group(35.69±4.78)g.Spleen index of the mice from the 100 mg/kg sodium butyrate+50％ Sishen pill group recovered to normal,showing significant difference from mice from the natural recovery group(P＜0.05).There were no significant differences in thymus index of mice from different groups(P＞0.05).After treatment,the mice intestinal microbiota began to recover,with no signifi-cant differences in the number of bacteria among groups(P＞0.05).Compared with the natural recovery group,the number of Escherichia coli in mice from each treatment group reduced significantly(P＜0.01),and the mice from 100 mg/kg sodium butyrate+50％ Sishen pill group had the smallest number of Escherichia coli.The number of Bifidobacteria in mice from the 100 mg/kg sodium butyrate+50％ Sishen pill group and the 50 mg/kg sodium bu-tyrate+75％ Sishen pill group recovered to the level of the normal group(P＞0.05).The mice from 100 mg/kg so-dium butyrate+50％ Sishen pill group showed a significant effect on the recovery of Lactobacillus number(P＜0.05).The amylase,lactase,and protease activities in mice from the natural recovery group were all higher than those from the normal group(all P＜0.05),and the enzyme activities in mice from the 100 mg/kg sodium butyrate+50％ Sishen pill group were closer to those from the normal group.Compared with the natural recovery group,lactase activity of mice from the 100％ Sishen pill group reduced significantly(P＜0.01),and the xylanase activity in mice from the 100 mg/kg sodium butyrate+50％ Sishen pill group was closest to the normal group.Conclusion The synergistic effect of sodium butyrate enhances the therapeutic efficacy of Sishen pill.100 mg/kg sodium buty-rate+50％ Sishen pill group showed significant improvement in mice mental status,diarrhea symptoms,intestinal enzyme activity,and microbial stability compared with other groups using sodium butyrate or Sishen pill alone.

Objective To explore the synergistic therapeutic effect of sodium butyrate and Sishen pill on mice with diarrhea with kidney-yang deficiency syndrome,and provide experimental evidence for the contemporary application of classical prescriptions.Methods The diarrhea with kidney-yang deficiency syndrome mouse model was construc-ted by gavage of adenine combined with Folium sennae.Mice were given 100％Sishen pill decoction,50 mg/kg so-dium butyrate+75％Sishen pill decoction,100 mg/kg sodium butyrate+50％Sishen pill decoction,200 mg/kg so-dium butyrate+25％Sishen pill decoction,and 300 mg/mL sodium butyrate decoction by intragastric administra-tion,respectively.General condition,food and water intake,anal temperature,body weight,fecal water content,organ index,intestinal microbiota,and enzyme activity of the mice were compared.Results After treatment,the general condition,food and water intake,anal temperature,and fecal water content of the mice gradually recovered.The body weight of mice from the natural recovery group,the 200 mg/kg sodium butyrate+25％ Sishen pill group,and the 50 mg/kg sodium butyrate+75％ Sishen pill group still showed statistical differences from the normal group(P＜0.05).The body weight of mice from the 100 mg/kg sodium butyrate+50％ Sishen pill group(34.23±4.93)g increased,close to the body weight of mice from the normal group(35.69±4.78)g.Spleen index of the mice from the 100 mg/kg sodium butyrate+50％ Sishen pill group recovered to normal,showing significant difference from mice from the natural recovery group(P＜0.05).There were no significant differences in thymus index of mice from different groups(P＞0.05).After treatment,the mice intestinal microbiota began to recover,with no signifi-cant differences in the number of bacteria among groups(P＞0.05).Compared with the natural recovery group,the number of Escherichia coli in mice from each treatment group reduced significantly(P＜0.01),and the mice from 100 mg/kg sodium butyrate+50％ Sishen pill group had the smallest number of Escherichia coli.The number of Bifidobacteria in mice from the 100 mg/kg sodium butyrate+50％ Sishen pill group and the 50 mg/kg sodium bu-tyrate+75％ Sishen pill group recovered to the level of the normal group(P＞0.05).The mice from 100 mg/kg so-dium butyrate+50％ Sishen pill group showed a significant effect on the recovery of Lactobacillus number(P＜0.05).The amylase,lactase,and protease activities in mice from the natural recovery group were all higher than those from the normal group(all P＜0.05),and the enzyme activities in mice from the 100 mg/kg sodium butyrate+50％ Sishen pill group were closer to those from the normal group.Compared with the natural recovery group,lactase activity of mice from the 100％ Sishen pill group reduced significantly(P＜0.01),and the xylanase activity in mice from the 100 mg/kg sodium butyrate+50％ Sishen pill group was closest to the normal group.Conclusion The synergistic effect of sodium butyrate enhances the therapeutic efficacy of Sishen pill.100 mg/kg sodium buty-rate+50％ Sishen pill group showed significant improvement in mice mental status,diarrhea symptoms,intestinal enzyme activity,and microbial stability compared with other groups using sodium butyrate or Sishen pill alone.

This study was aimed at understanding the relationships among the drug resistance and genome characteristics of group A Streptococcus in Jiangsu Province.A total of 149 group A Streptococcus strains were collected from hospitals between 2016 and 2023.Thirteen antimicrobial minimal inhibitory concentrations were detected with the micro-dilution broth method.The GAS strains were typed with emm genotyping analysis and whole genome sequencing,to determine the carriage rates of drug resistance genes and the evolutionary relationships among strains.The resistance rates of 149 GAS strains to erythromy-cin,tetracycline,and clindamycin exceeded 90％,whereas the strains showed sensitivity to 8 different antibiotics,including penicillin.Notably,the resistance rates to erythromycin,tetracycline,and clindamycin consistently increased over time.All strains were classified into 9 emm types,among which emm12 accounted for the highest proportion(77/149;51.68％).Signifi-cant statistical differences were observed among emm types,in terms of the drug resistance rate,number of resistant species,and prevalence of drug resistance genes.Furthermore,SNP evolutionary tree analysis revealed 3 distinct clusters within the GAS strains:emm12,emm1,and other emm types.emm 12 and emm1 were the dominant GAS strains in Jiangsu Province.Most isolates were resistant to erythromycin,tetracycline,and clindamycin.Differences in phenotypes and genomic characteris-tics were observed among emm types.

This study was aimed at understanding the relationships among the drug resistance and genome characteristics of group A Streptococcus in Jiangsu Province.A total of 149 group A Streptococcus strains were collected from hospitals between 2016 and 2023.Thirteen antimicrobial minimal inhibitory concentrations were detected with the micro-dilution broth method.The GAS strains were typed with emm genotyping analysis and whole genome sequencing,to determine the carriage rates of drug resistance genes and the evolutionary relationships among strains.The resistance rates of 149 GAS strains to erythromy-cin,tetracycline,and clindamycin exceeded 90％,whereas the strains showed sensitivity to 8 different antibiotics,including penicillin.Notably,the resistance rates to erythromycin,tetracycline,and clindamycin consistently increased over time.All strains were classified into 9 emm types,among which emm12 accounted for the highest proportion(77/149;51.68％).Signifi-cant statistical differences were observed among emm types,in terms of the drug resistance rate,number of resistant species,and prevalence of drug resistance genes.Furthermore,SNP evolutionary tree analysis revealed 3 distinct clusters within the GAS strains:emm12,emm1,and other emm types.emm 12 and emm1 were the dominant GAS strains in Jiangsu Province.Most isolates were resistant to erythromycin,tetracycline,and clindamycin.Differences in phenotypes and genomic characteris-tics were observed among emm types.

Butyric acid is a type of short chain fatty acid and an important nutrient in intestinal epithelial cells.In addition to its important role in intestinal health,it has application value in anti-tumor,treatment of neuritis and di-abetes.At the same time,based on the demand for green development in the livestock industry,its anti-inflammato-ry effect can avoid the abuse of antimicrobial agents.As a green,pollution-free,and residue-free new feed,butyric acid ensures the sustainable and healthy development of the livestock industry.This article mainly summarizes the production of butyric acid in the intestine,its effects on the balance of gut microbiota,digestion ability,and inflam-mation in humans and animals,elaborates its application in human health and animal production.

Lithocarpus litseifolius is rich in the chalcones phloridzin and trilobatin, the biosynthesis pathways of which have not been fully demonstrated. Chalcone synthase(CHS) is the first key rate-limiting enzyme in the biosynthesis of flavonoids in plants. To explore the functions of CHS gene family in chalcone synthesis of L. litseifolius, this study screened out two CHS genes(LlCHS1 and LlCHS2) from the transcriptome data of this plant, and then bioinformatics analysis and functional characterization were performed for the two genes. The bioinformatics analysis showed that LlCHS1 and LlCHS2 were acidic hydrophilic stable proteins with no transmembrane domain, composed of 395 and 390 amino acid residues, respectively. Both of them contained the characteristic amino acid sequence "WGVLFGFGPGL" and highly conserved active sites(Cys-164, Phe-215, His-303, and Asn-336) of the CHS family. The phylogenetic tree showed that LlCHS1 shared the same clade with similar genes in Aquilaria sinensis, and LlCHS2 was closely related to similar genes in Malus domestica. Under exogenous addition of phloretic acid, co-expression of LlCHS1 or LlCHS2 with Aa4CL from Aromatoleum aromaticum in Escherichia coli catalyzed the production of phloretin from phloretic acid. This study laid a theoretical foundation for revealing the functions of CHS in plants and provided new enzymatic modules for producing phloretin by synthetic biology.
Acyltransferases/chemistry* ; Phylogeny ; Plant Proteins/chemistry* ; Cloning, Molecular ; Amino Acid Sequence

Child ; Humans ; Lead ; Urban Population ; Nutritional Status ; Health Surveys ; China/epidemiology* ; Rural Population

In this study, the fatty acid desaturase gene FAD2 was cloned from Coix lacryma-jobi L. and its molecular structure and function were studied. The results showed that the full-length cDNA sequence of FAD2 gene was 936 bp encoding 311 amino acid residues. Bioinformatics prediction results showed that the protein encoded by the FAD2 gene was an alkaline hydrophilic unstable protein with a molecular weight of 34.87 kDa. It contained three transmembrane helix domain, and did not contain the signal peptide splicing site, and was most likely to be located in plasmid membrane. Compared with other similar genes in plants, it has only a histidine conserved site, His Box Ⅲ histidine site (HXXHH), suggesting its activity may be reduced. Phylogenetic tree analysis showed that FAD2 was closely related to monocotyledonous plants, especially Maize and Oryza sativa japonica Group, but farther from dicotyledonous plants. Therefore, it was inferred that FAD2 might have similar functions with similar genes in Maize and Oryza sativa japonica Group. In addition, the expression of FAD2 gene could be detected in Coix lacryma-jobi L. with high oil content, but not in low oil content of Coix lacryma-jobi L. In order to clarify the function of FAD2, the gene was heterologously expressed in sporomyces cerevisiae. The results showed that the protein encoded by FAD2 gene did not catalyze the formation of C18∶1 unsaturated fatty acid into C18∶2 unsaturated fatty acid. Therefore, it was speculated that the deletion of histidinine conserved site of FAD2 gene might lead to the decrease of protein activity or even inactivation. This study provides reference value for further understanding the molecular structure characteristics of fatty acid desaturase. At the same time, it laid a foundation for elucidating the biosynthetic pathway of Coix lacryma-jobi L.