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.

BACKGROUND: Approximately 40% of individuals with diabetes worldwide are at risk of developing diabetic kidney disease (DKD), which is not only the leading cause of kidney failure, but also significantly increases the risk of cardiovascular disease, causing significant societal health and financial burdens. This study aimed to describe the burden of DKD and explore its cross-country epidemiological status, predict development trends, and assess its risk factors and sociodemographic transitions. METHODS: Based on the Global Burden of Diseases (GBD) Study 2021, data on DKD due to type 1 diabetes (DKD-T1DM) and type 2 diabetes (DKD-T2DM) were analyzed by sex, age, year, and location. Numbers and age-standardized rates were used to compare the disease burden between DKD-T1DM and DKD-T2DM among locations. Decomposition analysis was used to assess the potential drivers. Locally weighted scatter plot smoothing and Frontier analysis were used to estimate sociodemographic transitions of DKD disability-adjusted life years (DALYs). RESULTS: The DALYs due to DKD increased markedly from 1990 to 2021, with a 74.0% (from 2,227,518 to 3,875,628) and 173.6% (from 4,122,919 to 11,278,935) increase for DKD-T1DM and DKD-T2DM, respectively. In 2030, the estimated DALYs for DKD-T1DM surpassed 4.4 million, with that of DKD-T2DM exceeding 14.6 million. Notably, middle-sociodemographic index (SDI) quintile was responsible for the most significant DALYs. Decomposition analysis revealed that population growth and aging were major drivers for the increased DKD DALYs in most regions. Interestingly, the most pronounced effect of positive DALYs change from 1990 to 2021 was presented in high-SDI quintile, while in low-SDI quintile, DALYs for DKD-T1DM and DKD-T2DM presented a decreasing trend over the past years. Frontiers analysis revealed that there was a negative association between SDI quintiles and age-standardized DALY rates (ASDRs) in DKD-T1DM and DKD-T2DM. Countries with middle-SDI shouldered disproportionately high DKD burden. Kidney dysfunction (nearly 100.0% for DKD-T1DM and DKD-T2DM), high fasting plasma glucose (70.8% for DKD-T1DM and 87.4% for DKD-T2DM), and non-optimal temperatures (low and high, 5.0% for DKD-T1DM and 5.1% for DKD-T2DM) were common risk factors for age-standardized DALYs in T1DM-DKD and T2DM-DKD. There were other specific risk factors for DKD-T2DM such as high body mass index (38.2%), high systolic blood pressure (10.2%), dietary risks (17.8%), low physical activity (6.2%), lead exposure (1.2%), and other environmental risks. CONCLUSIONS DKD markedly increased and varied significantly across regions, contributing to a substantial disease burden, especially in middle-SDI countries. The rise in DKD is primarily driven by population growth, aging, and key risk factors such as high fasting plasma glucose and kidney dysfunction, with projections suggesting continued escalation of the burden by 2030.
Humans ; Global Burden of Disease ; Risk Factors ; Male ; Female ; Disability-Adjusted Life Years ; Diabetic Nephropathies/epidemiology* ; Middle Aged ; Diabetes Mellitus, Type 2/epidemiology* ; Adult ; Diabetes Mellitus, Type 1/complications* ; Aged ; Adolescent ; Young Adult ; Quality-Adjusted Life Years

Objective To investigate the correlation between the triglyceride-glucose index(TyG),atherogenic index of plasma(AIP),systemic immune-inflammation index(SII),serum creatinine(SCr)and the severity of hyperlipidemic acute pancreatitis(HLAP).Methods A total of 156 HLAP patients admitted to Huzhou First People's Hospital from January 2020 to December 2024 were enrolled as subjects.They were divided into mild group(n=89)and moderately-severe/severe group(n=67)based on disease severity.Logistic regression analysis was used to identify independent risk factors.Spearman correlation analysis was used to examine the correlation between TyG,AIP,SCr,and HLAP severity.The predictive value of TyG,AIP,and SCr for HLAP were evaluated using receiver operating characteristic(ROC)curves.Results Levels of TyG,AIP,SII,and SCr were significantly higher in moderate-severe/severe group than in mild group(P＜0.05).Logistic regression analysis revealed that TyG,AIP,and SCr were independent risk factors for moderate-severe/severe HLAP(P＜0.05),whereas SII was not an independent risk factor.The severity of HLAP was positively correlated with early admission levels of TyG,AIP,and SCr.ROC curve analysis demonstrated that TyG showed superior diagnostic value compared to SCr and AIP.The combined indicators(SCr+AIP and SCr+TyG)outperformed single indicators in predictive value,with SCr+TyG exhibiting the highest predictive efficacy.Conclusion Early TyG,AIP,and SCr levels can serve as effective indicators for predicting disease severity in HLAP patients,and combined detection improves predictive accuracy.

Objective To investigate the correlation between the triglyceride-glucose index(TyG),atherogenic index of plasma(AIP),systemic immune-inflammation index(SII),serum creatinine(SCr)and the severity of hyperlipidemic acute pancreatitis(HLAP).Methods A total of 156 HLAP patients admitted to Huzhou First People's Hospital from January 2020 to December 2024 were enrolled as subjects.They were divided into mild group(n=89)and moderately-severe/severe group(n=67)based on disease severity.Logistic regression analysis was used to identify independent risk factors.Spearman correlation analysis was used to examine the correlation between TyG,AIP,SCr,and HLAP severity.The predictive value of TyG,AIP,and SCr for HLAP were evaluated using receiver operating characteristic(ROC)curves.Results Levels of TyG,AIP,SII,and SCr were significantly higher in moderate-severe/severe group than in mild group(P＜0.05).Logistic regression analysis revealed that TyG,AIP,and SCr were independent risk factors for moderate-severe/severe HLAP(P＜0.05),whereas SII was not an independent risk factor.The severity of HLAP was positively correlated with early admission levels of TyG,AIP,and SCr.ROC curve analysis demonstrated that TyG showed superior diagnostic value compared to SCr and AIP.The combined indicators(SCr+AIP and SCr+TyG)outperformed single indicators in predictive value,with SCr+TyG exhibiting the highest predictive efficacy.Conclusion Early TyG,AIP,and SCr levels can serve as effective indicators for predicting disease severity in HLAP patients,and combined detection improves predictive accuracy.

Microneedles (MNs) serve as a revolutionary paradigm in transdermal drug delivery, heralding a viable resolution to the formidable barriers presented by the cutaneous interface. This review examines MNs as an advanced approach to enhancing dermatological pathology management. It explores the complex dermis structure and highlights the limitations of traditional transdermal methods, emphasizing MNs' advantage in bypassing the stratum corneum to deliver drugs directly to the subdermal matrix. The discourse outlines the diverse typologies of MNs, including solid, coated, hollow, hydrogel, and dissolvable versions. Each type is characterized by its unique applications and benefits. The treatise details the deployment of MNs in the alleviation of cutaneous cancers, the administration of inflammatory dermatoses such as psoriasis and atopic dermatitis, and their utility in wound management. Additionally, the paper contemplates the prospects of MNs within the realm of aesthetic dermatology and the burgeoning market traction of cosmetic MN formulations. The review summarizes the scientific and commercial challenges to the clinical adoption of MN therapeutics, including dosage calibration, pharmacodynamics, biocompatibility, patient compliance, sterilization, mass production, and regulatory oversight. It emphasizes the need for ongoing research, innovation, and regulatory harmonization to overcome these obstacles and fully realize MNs' potential in treating skin diseases and improving patient welfare.

The abuse of antibiotics and other antimicrobial drugs has led to a significant increase in the prevalence of bacterial drug resistance. The advent of nanotechnology offers a promising way to address this challenge. Metal nanomaterials have emerged as a prominent class of antimicrobial agents, offering a number of advantages, including ease of preparation, high stability, potent efficacy against drug-resistant bacteria, and low toxicity. In this review, the antibacterial mechanisms of metal nanomaterials and the current research progress of gold, silver, copper, iron, platinum, palladium, and gallium nanomaterials and their application in the field of antibacterial were summarized with the aim of providing reference for the antibacterial use of metal nanomaterials.

Diseases caused by microbial infections, including bacteria, fungi, and viruses, are increasing every year. Currently, antibiotics are the primary treatment method for bacterial infections. However, over use of antibiotics can easily lead to bacterial resistance. Due to the broad-spectrum antibacterial properties of copper nanomaterials, they exhibit excellent antibacterial activity against both gram-negative bacteria and gram-positive bacteria. In this review, the preparation methods of copper nanomaterials were summarized, the antibacterial and antiviral effects of copper nanomaterials, and their applications in the fields of antibacterial and antiviral were discussed. Finally, the problems of copper nanomaterials in terms of toxicity and stability were summarized, and their future applications in the fields of antibacterial and antiviral were prospected.

The nuclear pore complex (NPC), one of the largest protein complexes in eukaryotes, serves as a physical gate to regulate nucleocytoplasmic transport. Here, we determined the 8 Å resolution cryo-electron microscopic (cryo-EM) structure of the outer rings containing nuclear ring (NR) and cytoplasmic ring (CR) from the Xenopus laevis NPC, with local resolutions reaching 4.9 Å. With the aid of AlphaFold2, we managed to build a pseudoatomic model of the outer rings, including the Y complexes and flanking components. In this most comprehensive and accurate model of outer rings to date, the almost complete Y complex structure exhibits much tighter interaction in the hub region. In addition to two copies of Y complexes, each asymmetric subunit in CR contains five copies of Nup358, two copies of the Nup214 complex, two copies of Nup205 and one copy of newly identified Nup93, while that in NR contains one copy of Nup205, one copy of ELYS and one copy of Nup93. These in-depth structural features represent a great advance in understanding the assembly of NPCs.
Animals ; Artificial Intelligence ; Cryoelectron Microscopy ; Nuclear Pore/ultrastructure* ; Oocytes/metabolism* ; Xenopus laevis

Chemotherapy has been a major option in clinic treatment of malignant tumors. However, single chemotherapy faces some drawbacks, such as multidrug resistance, severe side effects, which hinder its clinic application in tumor treatment. Multifunctional nanoparticles loading with chemotherapeutic agent and photosensitizer could be a promising way to efficiently conduct tumor combination therapy. In the current study, a novel pH-sensitive and bubble-generating mesoporous silica-based drug delivery system (denoted as M(a)D@PI-PEG-RGD) was constructed. Ammonium bicarbonate (NH

Malignant tumors are the second most important cause of death after cardiovascular and cerebrovascular diseases. Chemotherapeutic drugs for tumor treatment have strong toxic side effects. The common solution is to use nanoparticle as a carrier that can deliver drugs to tumor issues so as to kill the tumor cells. However, most of the current drug-carriers have a serious drug loss before reaching the tumor area, which makes the difficult control of drug release. Multi-stimulus responsive nano-carrier systems can overcome these drawbacks and make drug release controllable. pH/redox dual sensitive nano-carrier systems are currently hot research direction. In this paper, the research progress of pH/redox dual sensitive nano-carrier systems in recent years was reviewed in order to provide reference for relative researches.