Although teniposide(VM26)is widely used in the treatment of lymphoma,its poor water sol-ubility,low bioavailability and systemic toxicities still limit its clinical application.Nano-delivery systems are effective in increasing the bioavailability and reducing the toxicity of VM26,but there is an urgent need to overcome the problem of its non-specific targeting.Therefore,in this paper,we designed and constructed a hyaluronic acid-modified teniposide-targeted nano-delivery system(VM26-TNDS),and characterised its drug encapsulation rate,particle size and zeta potential.We also investigated the effects of VM26-TNDS on B-cell lymphoma cells with different expression of CD44 receptor,in terms of cellular targeting,inhibitory effect of proliferation,and induction of apoptosis and necrosis.The results showed that the drug encapsulation efficiency of VM26-TNDS exceeded 85％,and its liquid formulation could be stably stored at 4 ℃ for more than 6 months without precipitation.Based on CD44 receptor expression,Granta-519(high expression),Raji(medium-low expression)and SU-DHL-4(almost no expression)were screened for cellular experiments.Compared with VM26-NDS,the targeted modification could effec-tively reduce the uptake of VM26-TNDS by RAW264.7 and increase the uptake of VM26-TNDS by CD44 receptor-expressing lymphoma cells.The inhibitory proliferative effect and apoptotic necrosis-inducing a-bility of VM26-TNDS were stronger than those of VM26-NDS for Granta-519 and Raji cells,whereas there was no significant difference in the inhibitory effect on proliferation and ability to induce apoptosis and necrosis between VM26-NDS and VM26-TNDS in SU-DHL-4 cells,reflecting the targeting advantage for VM26-TNDS,as expected.However,its toxic effect on B-cell lymphoma cells only reflected the targeting advantage at some concentrations(0.25 μmol/L and 0.5 μmol/L),which met the expectation.The a-bove results indicate that a teniposide-targeted nano-delivery system,VM26-TNDS,has been successfully prepared in this study.VM26-TNDS improves the delivery efficiency of VM26 by targeting human B-cell lymphoma cells expressing the CD44 receptor,thus killing human B-cell lymphoma cells more effectively and overcoming the problem of non-specific targeting in drug delivery to improve the therapeutic effect.Its biological therapeutic effects and mechanisms still need to be proved by more in vitro and in vivo ex-perimental evidence.

Single-cell assay for transposase-accessible chromatin sequencing(scATAC-seq)is a power-ful technique for studying cellular heterogeneity and gene regulatory networks,widely applied in epigenet-ic research.However,the complexity of data analysis workflows and high programming requirements have limited its broader adoption among non-programmer researchers.To address this issue,we developed Sig-nac.UIO,a modular and visual scATAC-seq analysis platform based on the R Shiny framework,integra-ting mainstream tools such as Signac and Seurat.The platform includes ten key modules covering quality control,cell filtering,dimensionality reduction,clustering,differential analysis,cell annotation,path-way enrichment,motif analysis,and transcription factor footprinting.Through a graphical user interface,users can perform full analyses and obtain interactive visualization results.The platform's stability and u-tility have been validated using a public PBMC dataset and it is currently deployed online(https://xula-bgdpu.org.cn/Signac.UIO),providing an efficient and user-friendly tool for single-cell epigenomics re-search.

Single-cell assay for transposase-accessible chromatin sequencing(scATAC-seq)is a power-ful technique for studying cellular heterogeneity and gene regulatory networks,widely applied in epigenet-ic research.However,the complexity of data analysis workflows and high programming requirements have limited its broader adoption among non-programmer researchers.To address this issue,we developed Sig-nac.UIO,a modular and visual scATAC-seq analysis platform based on the R Shiny framework,integra-ting mainstream tools such as Signac and Seurat.The platform includes ten key modules covering quality control,cell filtering,dimensionality reduction,clustering,differential analysis,cell annotation,path-way enrichment,motif analysis,and transcription factor footprinting.Through a graphical user interface,users can perform full analyses and obtain interactive visualization results.The platform's stability and u-tility have been validated using a public PBMC dataset and it is currently deployed online(https://xula-bgdpu.org.cn/Signac.UIO),providing an efficient and user-friendly tool for single-cell epigenomics re-search.

Although teniposide(VM26)is widely used in the treatment of lymphoma,its poor water sol-ubility,low bioavailability and systemic toxicities still limit its clinical application.Nano-delivery systems are effective in increasing the bioavailability and reducing the toxicity of VM26,but there is an urgent need to overcome the problem of its non-specific targeting.Therefore,in this paper,we designed and constructed a hyaluronic acid-modified teniposide-targeted nano-delivery system(VM26-TNDS),and characterised its drug encapsulation rate,particle size and zeta potential.We also investigated the effects of VM26-TNDS on B-cell lymphoma cells with different expression of CD44 receptor,in terms of cellular targeting,inhibitory effect of proliferation,and induction of apoptosis and necrosis.The results showed that the drug encapsulation efficiency of VM26-TNDS exceeded 85％,and its liquid formulation could be stably stored at 4 ℃ for more than 6 months without precipitation.Based on CD44 receptor expression,Granta-519(high expression),Raji(medium-low expression)and SU-DHL-4(almost no expression)were screened for cellular experiments.Compared with VM26-NDS,the targeted modification could effec-tively reduce the uptake of VM26-TNDS by RAW264.7 and increase the uptake of VM26-TNDS by CD44 receptor-expressing lymphoma cells.The inhibitory proliferative effect and apoptotic necrosis-inducing a-bility of VM26-TNDS were stronger than those of VM26-NDS for Granta-519 and Raji cells,whereas there was no significant difference in the inhibitory effect on proliferation and ability to induce apoptosis and necrosis between VM26-NDS and VM26-TNDS in SU-DHL-4 cells,reflecting the targeting advantage for VM26-TNDS,as expected.However,its toxic effect on B-cell lymphoma cells only reflected the targeting advantage at some concentrations(0.25 μmol/L and 0.5 μmol/L),which met the expectation.The a-bove results indicate that a teniposide-targeted nano-delivery system,VM26-TNDS,has been successfully prepared in this study.VM26-TNDS improves the delivery efficiency of VM26 by targeting human B-cell lymphoma cells expressing the CD44 receptor,thus killing human B-cell lymphoma cells more effectively and overcoming the problem of non-specific targeting in drug delivery to improve the therapeutic effect.Its biological therapeutic effects and mechanisms still need to be proved by more in vitro and in vivo ex-perimental evidence.

Ureaplasma urealyticum (UU) is one of the most commonly occurring pathogens associated with genital tract infections in infertile males, but the impact of seminal UU infection in semen on intrauterine insemination (IUI) outcomes is poorly understood. We collected data from 245 infertile couples who underwent IUI at The First Affiliated Hospital of USTC (Hefei, China) between January 2021 and January 2023. The subjects were classified into two groups according to their UU infection status: the UU-positive group and the UU-negative group. We compared semen parameters, pregnancy outcomes, and neonatal birth outcomes to investigate the impact of UU infection on IUI outcomes. There were no significantly statistical differences in various semen parameters, including semen volume, sperm concentration, total and progressive motility, sperm morphology, leukocyte count, the presence of anti-sperm antibody, and sperm DNA fragmentation index (DFI), between the UU-positive and UU-negative groups of male infertile patients (all P > 0.05). However, the high DNA stainability (HDS) status of sperm differed between the UU-positive and UU-negative groups, suggesting that seminal UU infection may affect sperm nuclear maturation ( P = 0.04). Additionally, there were no significant differences in pregnancy or neonatal birth outcomes between the two groups (all P > 0.05). These results suggest that IUI remains a viable and cost-effective option for infertile couples with UU infection who are facing infertility issues.
Humans ; Male ; Ureaplasma Infections/complications* ; Female ; Infertility, Male/therapy* ; Ureaplasma urealyticum/isolation & purification* ; Pregnancy ; Adult ; Pregnancy Outcome ; Semen Analysis ; Insemination, Artificial ; Semen/microbiology* ; China

Objective To observe the clinical effect of acupuncture combined with Shenqi Huoxue Decoction in the treatment of adenomyosis of qi deficiency and blood stasis type.Methods Seventy patients with adenomyosis of qi deficiency and blood stasis type were randomly divided into observation group and control group,35 cases in each group.The control group was treated with Levonorgestrel-releasing intrauterine system,and the observation group was treated with acupuncture combined with Shenqi Huoxue Decoction on the basis of the treatment of the control group.One menstrual cycle was a course of treatment,and the treatment lasted for three courses.After 3 months of treatment,the clinical efficacy of the two groups was evaluated,and the changes of Endometriosis Health Profile-5(EHP-5)score,serum superoxide dismutase(SOD)and catalase(CAT)were observed in the two groups before and after treatment.The changes of serum carbohydrate antigen CA125,carbohydrate antigen 199(CA199)and human epididymis protein 4(HE4)levels were compared before and after treatment between the two groups.Results(1)The total effective rate was 97.14％(34/35)in the observation group and 77.14％(27/35)in the control group.The clinical efficacy of the observation group was superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After treatment,the levels of serum CA125,CA199 and HE4 in the two groups were significantly improved(P＜0.05),and the improvement of serum CA1 25,CA199 and HE4 levels in the observation group was significantly superior to that in the control group,the difference was statistically significant(P＜0.05).(3)After treatment,the levels of serum SOD and CAT in the two groups were significantly improved(P＜0.05),and the improvement of serum SOD and CAT levels in the observation group was significantly superior to that in the control group,the difference was statistically significant(P＜0.05).(4)After treatment,the EHP-5 score of quality of life in the two groups was significantly improved(P＜0.05),and the EHP-5 score of quality of life in the observation group was significantly superior to that in the control group,the difference was statistically significant(P＜0.05).Conclusion Acupuncture combined with Shenqi Huoxue Decoction in the treatment of adenomyosis of qi deficiency and blood stasis type can significantly improve the clinical symptoms of patients,regulate the levels of SOD and CAT,so as to improve the quality of life of patients,and the curative effect is significant.

Objective To investigate the effect and mechanism of proteasome inhibitor MG132 on memory impairment induced by chronic hypoxia in mice.Methods(1)A hypoxic model of the mouse midbrain dopaminergic neuron cell line MN9D was established using a hypoxia workstation.To observe the effects of hypoxia on the expression of TH,Ub-K48 and Ub-K63,MN9D cells were divided into normoxia group and hypoxia(12 h,24 h and 48 h)groups.To observe the effects of MG132 on the expression of the above-mentioned proteins,MN9D cells were divided into normoxia group,hypoxia group and hypoxia + MG132(25,50,100,200 μmol/L)group.(2)A mouse model of memory impairment was established using a hypobaric chamber.To observe the effects of hypobaric hypoxia on the expression of TH,Ub-K48 and Ub-K63 in the substantia nigra compacta(SNc)of mice,thirty C57BL/6 mice were randomly and equally divided into normoxia group and hypobaric hypoxia(3 d and 21 d)groups,10 in each group.To observe the effects of MG132 on spatial memory impairment induced by hypobaric hypoxia,twenty-four C57BL/6 mice were randomly and equally divided into normoxia group,hypobaric hypoxia 21 d group and hypobaric hypoxia 21 d+MG132 group,8 in each group.(3)The protein expression levels of TH,Ub-K48,and Ub-K63 in MN9D cells which were either subjected to different durations of hypoxia treatment or pre-treated with MG132 prior to hypoxia treatment were detected using Western blotting(WB).The novel object recognition test was used to detect the memory function of mice.Immunofluorescence was used to detect the proportion of positive immunoreactive area of TH response in the SNc region.The expression levels of TH,Ub-K48,and Ub-K63 in the SNc region were detected by WB.Results(1)Compared with normoxia group,MN9D cells in hypoxia 24 h group showed increasing expression of Ub-K48 and Ub-K63(P<0.05),and decreasing expression of TH(P<0.05),and MN9D cells in all hypoxia groups showed increasing expression of Ub-K48/TH and Ub-K63/TH(P<0.05).Compared with hypoxia group,MN9D cells showed decreasing expression of Ub-K48/TH and Ub-K63/TH in hypoxia + MG132 100 umol/L group and hypoxia + MG132 200 umol/L group(P<0.05).(2)Compared with the mice in normoxia group,mice in 3 d and 21 d hypobaric hypoxia groups showed decreasing expression of TH(P<0.001),and increasing expression of Ub-K48/TH and Ub-K63/TH(P<0.05)in the SNc region.Compared with normoxia group,the mice in 21 d hypobaric hypoxia group showed a lower new object recognition index(P<0.01),and the proportion of positive immunoreactive area of TH response in the SNc region(P<0.05).Compared with 21 d hypobaric hypoxia group,the mice in hypobaric hypoxia 21 d+MG132 group showed a higher new object recognition index(P<0.01).Conclusion The proteasome inhibitor MG132 could alleviate the memory impairment induced by chronic hypoxia in mice,and its mechanism may be related to the inhibition of Ub-K63 and Ub-K48,which in turn upregulates expression of TH in dopaminergic neurons.

Objective To investigate the effect and mechanism of rhubarb Tangluo pill on liver injury in type 2 diabetic rats.Methods ZDF(fa/fa)rats were given high-fat diet to induce type 2 diabetes model,and were randomly divided into model group,positive control group(0.18 g·kg-1 metformin)and experimental-L,-M,-H groups(0.54,1.08 and 2.16 g·kg-1 rhubarb Tangluo pill),with 8 rats in each group.Eight ZDF(fa/+)rats were selected as control group.The control group and model group were given equal volume of pure water once a day for 12 weeks.An oral glucose tolerance test(OGTT)was performed after administration.Fasting blood glucose level,body mass and liver mass of rats were measured and liver index was calculated.The contents of glutamic-pyruvic transaminase(GPT),glutamic oxalacetic transaminase(GOT),triglyceride(TG)and total cholesterol(TC)in serum were detected.The histomorphologic changes of liver were observed by hematoxylin-eosin(HE)staining and Masson staining.The protein expression of phosphorylated insulin receptor substrate 1(p-IRS1),phosphorylated protein kinase B(p-Akt)and glucose transporter 4(GLUT4)were detected by Western blotting.Results After administration,the fasting blood glucose levels of control group,model group,positive control group and experimental-H group were(4.71±0.45),(29.9±2.97),(15.28±4.52)and(13.84±1.55)mmol·L-1,respectively;the liver index were 2.31±0.46,4.03±0.18,3.37±0.23 and 3.38±0.24;the relative expression level of p-IRS1 protein were 1.00±0.36,4.00±0.11,1.62±0.27 and 1.90±0.17,respectively;the relative expression levels of p-Akt protein were 1.00±0.25,0.21±0.04,0.73±0.15 and 0.54±0.04,respectively;GLUT4 protein relative expression levels were 1.00±0.11,0.40±0.08,0.86±0.04 and 0.70±0.06,respectively.Compared with the model group,the above indexes in the experimental-H group were statistically significant(P＜0.01,P＜0.05).Conclusion Rhubarb Tanglu pill can effectively improve glycolipid metabolism and liver injury in type 2 diabetes mellitus,and its mechanism may be related to the activation of IRS1/Akt signaling pathway.

Objective To explore the protective mechanism of icariin on neuronal oxidative damage,providing a basic pharmacological basis for the treatment of cognitive impairment.Methods Glutamate was used to induce oxidative stress injury in HT22 cells.HT22 cells were divided into control group(normal cultured cells),model group(glutamate injury model)and experimental-L,-M,-H groups(5,10 and 20 μmol·L-1 icariin pretreatment for modeling,respectively).Cell proliferation was detected by cell counting kit-8(CCK-8)method;cytotoxicity was detected by lactate dehydrogenase(LDH)method;reactive oxygen species(ROS)levels were detected by flow cytometry;superoxide dismutase(SOD)levels were detected by biochemical kits;the expression levels of Kelch-like epichlorohydrin-related protein-1(Keap1),nuclear factor E2-related factor 2(Nrf2)were detected by Western blotting;the corresponding mRNA expression was detected by real-time fluorescence quantification polymerose chain reaction.Results The cell viability of control group,model group and experimental-L,-M,-H groups were(100.00±1.31)％,(66.38±2.44)％,(72.07±4.95)％,(82.41±3.57)％and(87.97±4.98)％;LDH release were(0.48±0.52)％,(18.82±2.09)％,(15.32±1.17)％,(10.37±1.39)％and(6.51±0.87)％;ROS level were(14.23±1.13)％,(41.74±1.60)％,(35.69±1.08)％,(33.28±1.69)％and(30.32±2.03)％;SOD levels were(54.84±1.17),(37.95±1.13),(48.02±1.28),(50.56±1.34)and(52.55±1.04)U·mg-1;Keap1 protein levels were 0.36±0.01,0.52±0.03,0.46±0.04,0.39±0.09 and 0.35±0.12;Nrf2 protein levels were 0.29±0.02,0.13±0.08,0.18±0.03,0.21±0.11 and 0.26±0.04;catalase(CAT)mRNA levels were 1.01±0.08,0.81±0.06,0.90±0.04,1.05±0.15 and 1.33±0.26;SOD mRNA levels were 1.09±0.12,0.83±0.03,0.86±0.08,0.94±0.08 and 1.09±0.16.Among the above indicators,the differences between the model group and the control group were statistically significant(all P＜0.01);the differences between the experimental-M,-H groups and the model group were statistically significant(P＜0.01,P＜0.05).Conclusion Icariin may activate the Keap1/Nrf2/antioxidant response element(ARE)signaling pathway,regulate the expression of related proteins,and reduce the level of ROS to effectively alleviate oxidative stress injury in neuronal cells.