Objective: To prepare the erythrocyte-liposome drug delivery system to enhance the therapeutic effect of drugs on tumors and inhibit tumor metastasis. Methods: This study prepared and characterized paclitaxel (PTX)-plerixafor (AMD3100) liposomes (Lips), developed the erythrocyte-liposome drug delivery system, and evaluated its targeting efficiency and therapeutic efficacy through a series of in vitro cellular and in vivo animal experiments. Results: The particle size of PTX-AMD-Lips was (186.4±0.83) nm. Drug encapsulation efficiency of PTX-AMD-Lips was (75.50±5.27)% for PTX and (88.31±2.45)% for AMD. The Binding efficiency between RBC and liposomes in the drug delivery system was (69.93±2.55)%. Vitro cellular experiments revealed that PTX-AMD-Lips significantly inhibited tumor cell migration. In vivo animal experiments, the erythrocyte-liposome drug delivery system significantly increased drug accumulation in the lungs. At the experimental endpoint, the quantitative fluorescence signal of tumor size measured (4.04±0.44)×10 for the PTX-Lips group, and (5.14±3.40)×10 for the RBC-PTX-AMD-Lips group. Conclusion: The erythrocyte-liposome drug delivery system could enhance the lung-specific targeting capability of liposomes, kill tumor cells and suppress further metastasis effectively.

Objective To establish mouse models exposed to different doses of neodymium oxide via tracheal instillation,and to investigate the mechanisms underlying brain tissue damage induced by neodymium oxide exposure in mice.Methods Forty-eight male C57/BL6 mice were randomly assigned to four groups:the control group,the low-dose group,the medium-dose group,and the high-dose group.The low-dose,medium-dose,and high-dose groups received 62.5 mg/mL,125 mg/mL,and 250 mg/mL neodymium oxide,respectively,via non-exposed tracheal instillation.The control group received an equivalent volume of saline using the same administration method.After 35 days,the mice were euthanized,and brain tissues were collected.RT-PCR was used to assess the mRNA expression changes of Claudin-5 and Occludin.Western blot analysis was performed to evaluate the expression changes of Claudin-5 and Occludin tight junction proteins,as well as the expression changes of MMP-2 and MMP-9 in the brain tissues.Additionally,the expression of the RhoA/ROCK2 signaling pathway and downstream cofilin protein was examined.Changes in oxidative stress markers,including MDA,T-AOC,and NO,were measured using a kit method.Results The mRNA expression of Claudin-5 was significantly reduced in the middle-dose and high-dose groups compared to the control group(P<0.05).Similarly,the mRNA expression of Occludin was significantly lower in the low-dose,medium-dose,and high-dose groups compared to the control group(P<0.05).Additionally,the protein expression of Claudin-5,MMP-2,and Occludin was significantly decreased in the low-dose,medium-dose,and high-dose groups compared to the control group(P<0.05).The protein expression of MMP-9 and RhoA was also signifi-cantly lower in the medium-dose and high-dose groups compared to the control group(P<0.05).Furthermore,the protein expression of ROCK2 and p-cofilin in the high-dose group was significantly lower than that in the control group(P<0.05).The content of MDA and T-AOC was significantly lower in the medium-dose and high-dose groups compared to the control group(P<0.05),and the content of NO in the high-dose group was significantly lower than that in the control group(P<0.05).Conclusion Exposure to neodymium oxide results in increased permeability of the blood-brain barrier in mice,leading to oxidative stress,inflammatory responses,and activation of the RhoA/ROCK2 signaling pathway.

Sleeve gastrectomy with transit bipartition is a novel bariatric and metabolic procedure providing significant metabolic benefits while minimizing the risk of malnutrition. However, due to the technical complexity of the Roux-en-Y transit bipartition configuration, several derivative procedures have been developed in clinical practice, including single anastomosis sleeve ileal bypass (SASI), single anastomosis sleeve jejunal bypass (SAS-J), and sleeve gastrectomy with Braun anasto-mosis transit bipartition (B-TB). These procedures vary in complexity, weight loss and metabolic efficacy, nutritional impact, and anti-reflux properties. SASI offers technical simplicity but raises concerns about bile reflux. SAS-J emphasizes nutritional safety, whereas B-TB incorporates a Braun anastomosis to enhance anti-reflux protection. The authors review and compare the clinical charac-teristics and indications of these procedures, aiming to provide a reference for surgeons in selecting individualized metabolic and bariatric surgical strategies.

Hedysari radix is the characteristic chi-nese medicine of Gansu Province,with"MiCang Hedysari radix"as the best.Modern pharmacologi-cal research has shown that it has polysaccharides and flavonoids,which have good anti-tumor effects and can inhibit the occurrence and development of various cancers,such as lung cancer,liver cancer,and breast cancer.Cancer is ranked as the second leading cause of death in the world,and the mor-bidity and mortality rates are increasing year by year,seriously affecting the quality of life.At pres-ent,with the modernization of Traditional Chinese Medicine(TCM),there has been a significant break-through in the treatment of malignant tumors with TCM.Based on this,by collating the relevant litera-ture at home and abroad in recent years,the anti-tumor effects and mechanisms of Hedysari radix and its active ingredients are summarized to pro-vide a scientific basis for the study of elucidating the material basis of the anti-tumor effects of He-dysari radix and to promote the development of the Hedysari radix industry.

Hedysari radix is the characteristic chi-nese medicine of Gansu Province,with"MiCang Hedysari radix"as the best.Modern pharmacologi-cal research has shown that it has polysaccharides and flavonoids,which have good anti-tumor effects and can inhibit the occurrence and development of various cancers,such as lung cancer,liver cancer,and breast cancer.Cancer is ranked as the second leading cause of death in the world,and the mor-bidity and mortality rates are increasing year by year,seriously affecting the quality of life.At pres-ent,with the modernization of Traditional Chinese Medicine(TCM),there has been a significant break-through in the treatment of malignant tumors with TCM.Based on this,by collating the relevant litera-ture at home and abroad in recent years,the anti-tumor effects and mechanisms of Hedysari radix and its active ingredients are summarized to pro-vide a scientific basis for the study of elucidating the material basis of the anti-tumor effects of He-dysari radix and to promote the development of the Hedysari radix industry.

Sleeve gastrectomy with transit bipartition is a novel bariatric and metabolic procedure providing significant metabolic benefits while minimizing the risk of malnutrition. However, due to the technical complexity of the Roux-en-Y transit bipartition configuration, several derivative procedures have been developed in clinical practice, including single anastomosis sleeve ileal bypass (SASI), single anastomosis sleeve jejunal bypass (SAS-J), and sleeve gastrectomy with Braun anasto-mosis transit bipartition (B-TB). These procedures vary in complexity, weight loss and metabolic efficacy, nutritional impact, and anti-reflux properties. SASI offers technical simplicity but raises concerns about bile reflux. SAS-J emphasizes nutritional safety, whereas B-TB incorporates a Braun anastomosis to enhance anti-reflux protection. The authors review and compare the clinical charac-teristics and indications of these procedures, aiming to provide a reference for surgeons in selecting individualized metabolic and bariatric surgical strategies.

Objective To establish mouse models exposed to different doses of neodymium oxide via tracheal instillation,and to investigate the mechanisms underlying brain tissue damage induced by neodymium oxide exposure in mice.Methods Forty-eight male C57/BL6 mice were randomly assigned to four groups:the control group,the low-dose group,the medium-dose group,and the high-dose group.The low-dose,medium-dose,and high-dose groups received 62.5 mg/mL,125 mg/mL,and 250 mg/mL neodymium oxide,respectively,via non-exposed tracheal instillation.The control group received an equivalent volume of saline using the same administration method.After 35 days,the mice were euthanized,and brain tissues were collected.RT-PCR was used to assess the mRNA expression changes of Claudin-5 and Occludin.Western blot analysis was performed to evaluate the expression changes of Claudin-5 and Occludin tight junction proteins,as well as the expression changes of MMP-2 and MMP-9 in the brain tissues.Additionally,the expression of the RhoA/ROCK2 signaling pathway and downstream cofilin protein was examined.Changes in oxidative stress markers,including MDA,T-AOC,and NO,were measured using a kit method.Results The mRNA expression of Claudin-5 was significantly reduced in the middle-dose and high-dose groups compared to the control group(P<0.05).Similarly,the mRNA expression of Occludin was significantly lower in the low-dose,medium-dose,and high-dose groups compared to the control group(P<0.05).Additionally,the protein expression of Claudin-5,MMP-2,and Occludin was significantly decreased in the low-dose,medium-dose,and high-dose groups compared to the control group(P<0.05).The protein expression of MMP-9 and RhoA was also signifi-cantly lower in the medium-dose and high-dose groups compared to the control group(P<0.05).Furthermore,the protein expression of ROCK2 and p-cofilin in the high-dose group was significantly lower than that in the control group(P<0.05).The content of MDA and T-AOC was significantly lower in the medium-dose and high-dose groups compared to the control group(P<0.05),and the content of NO in the high-dose group was significantly lower than that in the control group(P<0.05).Conclusion Exposure to neodymium oxide results in increased permeability of the blood-brain barrier in mice,leading to oxidative stress,inflammatory responses,and activation of the RhoA/ROCK2 signaling pathway.

Purpose: Myofibroblastic cancer-associated fibroblasts (myCAFs) are important components of the tumor microenvironment closely associated with tumor stromal remodeling and immunosuppression. This study aimed to explore myCAFs marker gene biomarkers for clinical diagnosis and therapy for patients with bladder cancer (BC). Materials and Methods: BC single-cell RNA sequencing (scRNA-seq) data were obtained from the National Center for Biotechnology Information Sequence Read Archive. Transcriptome and clinical data were downloaded from The Cancer Genome Atlas and the Gene Expression Omnibus databases. Subsequently, univariate Cox and LASSO (Least Absolute Shrinkage and Selection Operator regression) regression analyses were performed to construct a prognostic signature. Immune cell activity was estimated using single-sample gene set enrichment analysis whilst the TIDE (tumor immune dysfunction and exclusion) method was employed to assess patient response to immunotherapy. The chemotherapy response of patients with BC was evaluated using genomics of drug sensitivity in cancer. Furthermore, Immunohistochemistry was used to verify the correlation between MAP1B expression and immunotherapy efficacy. The scRNA-seq data were analyzed to identify myCAFs marker genes. Results: Combined with bulk RNA-sequencing data, we constructed a two-gene (COL6A1 and MAP1B) risk signature. In patients with BC, the signature demonstrated outstanding prognostic value, immune infiltration, and immunotherapy response. This signature served as a crucial guide for the selection of anti-tumor chemotherapy medications. Additionally, immunohistochemistry confirmed that MAP1B expression was significantly correlated with immunotherapy efficacy. Conclusions Our findings revealed a typical prognostic signature based on myCAF marker genes, which offers patients with BC a novel treatment target alongside theoretical justification.

Proteins with specific functions and characteristics play a crucial role in biomedicine and nanotechnology. De novo protein design enables the customization of sequences to produce proteins with desired structures that do not exist in the nature. In recent years, with the rapid development of artificial intelligence (AI), deep learning-based generative models have increasingly become powerful tools, enabling the design of functional proteins with atomic-level precision. This article provides an overview of the evolution of de novo protein design, with focus on the latest algorithmic models, and then analyzes existing challenges such as low design success rates, insufficient accuracy, and dependence on experimental validation. Furthermore, this article discusses the future trends in protein design, aiming to provide insights for researchers and practitioners in this field.
Artificial Intelligence ; Proteins/chemistry* ; Algorithms ; Protein Engineering/methods* ; Deep Learning

Objective:Preliminary explore the safety and efficacy of using only vitamin K antagonists without antiplatelet therapy after left ventricular assist devices (LVAD) implantation.Methods:This is a cohort study. Patients who underwent HeartCon LVAD implantation in TEDA International Cardiovascular Hospital from September 2020 to September 2022 were included. Oral warfarin sodium was given on postoperative days 1 to 2, with the target international standardized ratio (INR) of 2.0 to 2.5. Follow-up until September 2022, survival, INR level and occurrence of bleeding and thrombosis were recorded. Survival analysis was performed by the Kaplan-Meier method (censored for heart transplantation).Results:A total of 22 patients, including 16 male patients (72.7%), aged (51.0±13.3) years, were included. The duration of HeartCon LVAD support was (458±166) days and the INR during support was 2.28±0.26. One patient underwent the heart transplant at 307 d after implantation. One patient (4.5%) occured cardiac tamponade, two patients (9.1%) occured hemorrhagic stroke, five patients (22.7%) occured gastrointestinal bleeding, four patients (18.2%) occured gingival hemorrhage, two patients (9.1%) occured epistaxis, one patient (4.5%) occurred ischemic stroke, one patient (4.5%) occured pump thrombosis, and one patient (4.5%) occured aortic valve thrombosis. The survival rates were 100%, 95%, 95%, and 95% at 3 months, 6 months, 1 year, 2 years after implantation respectively.Conclusion:The single antithrombotic strategy using warfarin (target INR 2.0-2.5) without antiplatelet for patients with implantations of HeartCon type LVAD may be safe and effective.