Triple-negative breast cancer (TNBC) is a highly aggressive malignancy predominantly managed via chemotherapy. Our clinical sample analysis revealed a significant correlation between elevated CD24 expression in TNBC tumor cells and patient survival rates. We developed a novel antibody-drug conjugate (ADC), named HN03, consisting of an antibody with engineered cysteines for site-specific conjugation with a low toxic nitric oxide (NO) precursor as its payload through a novel Pt(IV)-mediated bioorthogonal self-cleavable linker. HN03 specifically targets tumor cells expressing high levels of CD24, concurrently generating cisplatin and releasing NO upon activation. HN03 also exhibited potent in vitro and in vivo antitumor activity. It significantly reduced tumor growth at various doses, prevented tumor metastasis, with markedly lower toxicity than traditional chemotherapy agents. We found that a key mechanism of its action involved inducing apoptosis and endoplasmic reticulum stress, substantially decreasing the number of M2-type macrophages. Overall, HN03 stands out as a promising therapeutic option for TNBC, offering a targeted treatment with reduced side effects and the potential for improved outcomes. Furthermore, using Pt(IV) in the linker and an NO precursor as the payload enhances the versatility of the Antibody-NO donor Conjugate (ANC), offering new avenues for the design of the next generation of ADCs.

In current clinical practice, various dermal templates and skin substitutes are used to enhance wound healing. However, the role of wound commensal microbiome in regulating scaffold performance and the healing process remains unclear. In this study, we investigated the influence of both natural and synthetic scaffolds on the wound commensal microbiome and wound repair in three distinct models including diabetic wounds, burn injuries, and germ-free (GF) wounds. Remarkably, synthetic electrospun polycaprolactone (PCL) scaffolds were observed to positively promote microbiome diversity, leading to enhanced diabetic wound healing compared to the natural scaffolds Integra® (INT) and MatriDerm® (MAD). In contrast, both natural and synthetic scaffolds exhibited comparable effects on the diversity of the microbiome and the healing of burn injuries. In GF wounds with no detectable microorganisms, a reversed healing rate was noted showing natural scaffold (MAD) accelerated wound repair compared to the open or the synthetic scaffold (PCL) treatment. Furthermore, the response of the wound commensal microbiome to PCL scaffolds appears pivotal in promoting anti-inflammatory factors during diabetic wound healing. Our results emphasize that the wound commensal microbiome, mediated by different scaffolds plays an important role in the wound healing process.

The glymphatic system (GS) is an essential waste clearance pathway in the central nervous system, playing a crucial role in the occurrence and progression of cerebrovascular diseases. In recent years, advancements in imaging techniques have provided important tools for assessing the structure and dynamics of the GS, further advancing its research in patients with cerebrovascular disease. This article reviews various imaging evaluation methods and clinical significance of GS in patients with cerebrovascular disease, aiming to provide a new perspective for a deeper understanding of the pathophysiological mechanisms and clinical practice of cerebrovascular disease.

Objective To develop a machine learning(ML)-based prediction model for assessing the therapeutic effects of resveratrol(RES)on the pathological damage of acute pancreatitis(AP),and to optimize RES administration strategies for AP through validation using an animal model.Methods AAn ML-based prediction model was constructed using published data.Interpretability analysis was applied to identify high-efficacy zones within the parameter space of administration dose and frequency,which was followed by rigorous screening to select the optimal dosing strategy that balanced therapeutic efficacy and experimental feasibility.A total of 32 C57BL/6 mice were randomly assigned to 4 groups(n=8 per group),including a control group(Ctrl),an AP model group induced by caerulein(CER)and referred to as CER-AP,a treatment group receiving RES via intraperitoneal injection(RES i.p.),and a treatment group receiving RES via intragastric gavage(RES i.g.).The Ctrl group received intraperitoneal injection of normal saline.The CER-AP and the treatment groups were induced with 10 intraperitoneal injections of CER at 50 μg/kg.RES was administered to the RES i.p.and RES i.g.groups according to the optimal dose and timing predicted by the ML model.Blood and tissue samples were collected 12 hours after the experiment started.Results The gradient boosting decision tree model,optimized via Hyperopt,yielded the best performance,predicting that the optimal dose and administration frequency were 19.992 mg/kg and 3.828 times,respectively.Accordingly,a regimen of 20 mg/kg RES,administered four times,was used in the animal experiments.Compared with the Ctrl group,the CER-AP group exhibited higher pancreatic pathology scores and elevated levels of serum amylase,lipase,pancreatic myeloperoxidase,and trypsin,with all differences reaching statistical significance(all P<0.05).The administration of 20 mg/kg RES via both intraperitoneal injection and intragastric gavage mitigated pancreatic inflammatory cell infiltration and necrosis,improved the overall pathology score,and reduced serum amylase,lipase,and pancreatic myeloperoxidase levels to varying degrees(all P<0.05).Conclusion A regimen of 20 mg/kg RES administered four times effectively alleviates the severity of CER-induced AP.The therapeutic benefits appear to arise from a multi-target regulatory network that simultaneously suppresses inflammatory cascades,mitigates oxidative stress,and reduces apoptosis,thereby reducing pancreatic tissue damage and systemic inflammatory responses.

The in-depth research of artificial intelligence in the medical field has greatly improved the workflow and diagnostic ability of diagnostic radiology.This article focuses on artificial intelligence technology in the field of interventional medicine,and enumerates its potential application scenarios,including improving image analysis capabilities to assist diagnosis and predict treatment response.It also describes the challenges that need to be overcome for practical application.Finally,with the continuous development of artificial intelligence in interventional medicine,artificial intelligence will further optimize the channels of interventional medicine and bring revolutionary changes to the clinical practice of interventional medicine.

OBJECTIVE To explore the optimal parameters of simmered Rhei Radix et Rhizoma and the correlation between the chroma values and the intrinsic composition of simmered Rhei Radix et Rhizoma decoction pieces powder.METHODS The single-factor-response surface method was used to investigate the simmering temperature,simmering time,paper dosage and plant ash dos-age,the response surface experiment was carried out on the basis of the single factor experiment,the appearance traits,total anthraqui-nones,free anthraquinones,leachables,sennoside A and B contents were taken as indicators,the analytic hierarchy process(AHP)was used to give weights to each index,and the process was optimized.The chroma values of raw and simmered products were deter-mined by electronic eye,the correlation and regression analysis were carried out by SPSS22.0 software,and the chroma-component re-gression equation was constructed.RESULTS The optimal process of simmering Rhei Radix et Rhizoma was 140 ℃,5 times of plant ash,2 layers of wet paper wrapped and being simmered for 2.5 h.CONCLUSION The simmering process of Rhei Radix et Rhizoma optimized by AHP combined with response surface method is reasonable and feasible,the color of decoction pieces has a significant correlation with the component content,and the regression equation constructed is reliable,which can predict the intrinsic component content of decoction pieces through chroma values.

Objective The aim of this study was to clarify the role and mechanism of Pseudomonas aeruginosa vaccine subunit OprI in the fusion protein vaccine rePO(PcrV-OprI).Methods The in vitro stability of rePO,PcrV and OprI at 4 ℃,25 ℃,and 37 ℃ was examined.After immunizing mice with rePO,OprI and PcrV,respectively,the specific antibody potency in serum and the proportion of cells secreting IFN-γ and IL-4 in the spleen were examined;Additionally,detection of the levels of protein uptake by DC2.4 cells in vitro using laser confocal microscopy and flow cytometry,and their ability to promote the maturation of mouse bone marrow-derived dendritic cells(BMDC).Results The heat stability of fusion protein rePO was significantly better than that of PcrV.The induced anti-PcrV IgG and anti-OprI IgG potency of rePO was significantly higher than that of monomeric PcrV and OprI.Additionally,the number of cells secreting IFN-γ and IL-4 induced by immunization with rePO was significantly higher than that of PcrV and OprI.The uptake rate of fusion protein rePO by DC2.4 cells was significantly higher than that of PcrV and OprI.Furthermore,rePO promoted the maturation of mouse BMDC more effectively than PcrV and OprI.Conclusion OprI in the fusion protein rePO can significantly improve its thermal stability and immunogenicity,which lays the foundation for the successful development of Pseudomonas aeruginosa vaccine.

OBJECTIVE To explore the optimal parameters of simmered Rhei Radix et Rhizoma and the correlation between the chroma values and the intrinsic composition of simmered Rhei Radix et Rhizoma decoction pieces powder.METHODS The single-factor-response surface method was used to investigate the simmering temperature,simmering time,paper dosage and plant ash dos-age,the response surface experiment was carried out on the basis of the single factor experiment,the appearance traits,total anthraqui-nones,free anthraquinones,leachables,sennoside A and B contents were taken as indicators,the analytic hierarchy process(AHP)was used to give weights to each index,and the process was optimized.The chroma values of raw and simmered products were deter-mined by electronic eye,the correlation and regression analysis were carried out by SPSS22.0 software,and the chroma-component re-gression equation was constructed.RESULTS The optimal process of simmering Rhei Radix et Rhizoma was 140 ℃,5 times of plant ash,2 layers of wet paper wrapped and being simmered for 2.5 h.CONCLUSION The simmering process of Rhei Radix et Rhizoma optimized by AHP combined with response surface method is reasonable and feasible,the color of decoction pieces has a significant correlation with the component content,and the regression equation constructed is reliable,which can predict the intrinsic component content of decoction pieces through chroma values.

Objective The aim of this study was to clarify the role and mechanism of Pseudomonas aeruginosa vaccine subunit OprI in the fusion protein vaccine rePO(PcrV-OprI).Methods The in vitro stability of rePO,PcrV and OprI at 4 ℃,25 ℃,and 37 ℃ was examined.After immunizing mice with rePO,OprI and PcrV,respectively,the specific antibody potency in serum and the proportion of cells secreting IFN-γ and IL-4 in the spleen were examined;Additionally,detection of the levels of protein uptake by DC2.4 cells in vitro using laser confocal microscopy and flow cytometry,and their ability to promote the maturation of mouse bone marrow-derived dendritic cells(BMDC).Results The heat stability of fusion protein rePO was significantly better than that of PcrV.The induced anti-PcrV IgG and anti-OprI IgG potency of rePO was significantly higher than that of monomeric PcrV and OprI.Additionally,the number of cells secreting IFN-γ and IL-4 induced by immunization with rePO was significantly higher than that of PcrV and OprI.The uptake rate of fusion protein rePO by DC2.4 cells was significantly higher than that of PcrV and OprI.Furthermore,rePO promoted the maturation of mouse BMDC more effectively than PcrV and OprI.Conclusion OprI in the fusion protein rePO can significantly improve its thermal stability and immunogenicity,which lays the foundation for the successful development of Pseudomonas aeruginosa vaccine.

Furry animal allergens, particularly cat and dog hair and dander, are common allergens in indoor environments, affecting the health of people world widely. Key sensitizing components such as Fel d 1 from cats and Can f 1 from dogs have been extensively studied and identified by the scientific community. Component resolved diagnosis (CRD) technology in modern diagnostic methods provides an accurate way to identify and distinguish these components, which is extremely important for the prevention of furry animal allergies and the formulation of personalized treatment strategies. To enhance the understanding of furry animal component diagnosis and promote the alignment of the Chinese discipline of allergology with international standards, this article interprets and explains the content of the "Molecular Allergology User′s Guide 2.0" recently released by the European Academy of Allergy and Clinical Immunology. It focuses on the epidemiological characteristics of furry animal components, the diversity of allergen protein families, and their clinical diagnosis and management.