Periodontitis is a chronic inflammatory disease caused by dysbiosis of the periodontal microbiome, threatening both oral and systemic health. Current prevention and treatment strategies for periodontitis mainly rely on mechanical therapy, with antibiotics used as supplements. However, limitations of mechanical therapy and increasing antibiotic resistance have prompted the exploration of new adjunctive strategies. Probiotic therapy, particularly Lacticaseibacillus rhamnosus (L. rhamnosus), formerly known as Lactobacillus rhamnosus, has emerged as a promising approach due to its ability to modulate periodontal microecology. L. rhamnosus exerts therapeutic effects by inhibiting pathogens, modulating immune responses, and promoting tissue repair. L. rhamnosus has been applied in various forms for the adjuvant treatment of periodontitis and numerous clinical trials have confirmed its safety and effectiveness, indicating broad potential for application. Nevertheless, current clinical studies still face challenges such as unclear strain-specific effects and a lack of standardized administration protocols. Future research should investigate the mechanisms of different strains and evaluate targeted interventions in diverse patient populations to advance the clinical use of probiotic therapies.

Inflammatory responses associated with pyroptosis have been shown to promote reactive oxygen species (ROS) production. Among these ROS, hypochlorite (ClO-) plays a pivotal role in regulating inflammatory progression. Herein, red-emissive carbon dots (N-CDs) with a maximum emission at 611 nm and a fluorescence quantum yield of 24.1% were developed. The N-CDs exhibit sensitive and selective fluorescence modulation toward ClO-, achieving a low detection limit of 0.056 μM. The N-CDs function as versatile fluorescent nanoprobes for monitoring exogenous ClO- dynamics in living cells, evaluating inflammatory status in cellular and zebrafish models, and assessing gouty arthritis in rats. Notably, the N-CDs enable real-time visualization of pyroptosis in living cells through distinct fluorescence signal evolution. Such fluorescence modulation provides a reliable readout for monitoring pyroptosis-associated oxidative stress. This work establishes a sensitive and specific platform for ClO- detection in inflammatory environments and highlights the potential applicability of red-emissive carbon dots for dynamic monitoring of inflammation-related cellular processes.

The type VI secretion system (T6SS) is an important fitness determinant of Salmonella enterica serovar Typhimurium (S. Typhimurium) during host colonization and bacterial competition. Tldi1 has been identified as an immunity protein associated with a T6SS antibacterial toxin-immunity module, but its contribution to avian infection remains unclear. This study investigated whether Tldi1 affects the infection outcome of S. Typhimurium in young chickens. Three-day-old Hy-Line Brown chickens were challenged with the wild-type strain SL1344, a tldi1 deletion mutant, or a complemented strain. Clinical signs, body weight, liver and spleen indices, splenic bacterial loads, tissue pathology, cecal mucin staining, inflammatory cytokine expression, intestinal barrier-related gene expression, and cecal microbiota composition were evaluated. Compared with wild-type infection, the tldi1 deletion mutant caused milder clinical signs, lower liver and spleen indices, reduced splenic bacterial loads, and attenuated histopathological lesions in the liver, spleen, ileum, and cecum. The mutant also induced lower expression of several pro-inflammatory cytokine genes and partially alleviated the downregulation of intestinal barrier-related genes. Complementation of tldi1 largely restored the wild-type infection phenotype. Cecal 16S rRNA sequencing showed that tldi1 deletion was associated with altered microbial community features and reduced inter-individual dispersion; however, overall beta-diversity differences were not statistically significant. These findings indicate that Tldi1 contributes to the in vivo fitness and infectionassociated pathology of S. Typhimurium in chickens. The results provide a basis for further investigation of T6SS toxin-immunity modules as potential targets for controlling Salmonella infection in poultry.

IntroductionType VI secretion system (T6SS) is a key bacterial secretion device in Salmonella enterica serovar Typhimurium (S. Typhimurium), responsible for translocating effectors to mediate bacterial-host interaction. Tldi1, a well-characterized immunity protein encoded in the T6SS gene cluster, specifically neutralizes the cognate toxin Tlde1 to prevent bacterial “friendly fire”. However, there is still a lack of systematic and in-depth research on the functions of Tldi1 at present. In order to elucidate the phenotype and toxicity effects of Tldi1 deficiency on S. Typhimurium, this study used S. Typhimurium SL1344 as a model strain and explored the role of Tldi1 toxicity on bacterial ecological adaptability and infection process through multi-level experiments.MethodsFirstly, molecular bioinformatics approaches were employed to analyze the physicochemical properties, hydrophilicity, hydrophobicity, transmembrane regions, subcellular localization, as well as secondary and tertiary structures of the Tldi1 protein. Secondly, a tldi1-deficient mutant of S. Typhimurium was constructed via homologous double crossover recombination, and alterations in its biological characteristics were analyzed. Finally, a mouse infection model was used to investigate the effect of tldi1 deletion on the infection progression of S. Typhimurium.ResultsThe results showed that compared with the wild-type (WT) strain, the Δtldi1 strain exhibited reduced splenic colonization, and regulated host inflammation, while these phenotypes were reversed in the Δtldi1/pΔtldi1 strain.DiscussionTldi1, as a key immunity protein for Tlde1 neutralization, indirectly regulates the environmental adaptability and host immune homeostasis of S. Typhimurium, providing new insights into the function of T6SS immunity proteins.

Perfluorooctane sulfonate (PFOS), a prevalent perfluoroalkyl substance (PFAS), is widely present in various environmental media, animals, and even human bodies. It primarily accumulates in the liver, contributing to the disruption of hepatic metabolic homeostasis. However, the precise mechanism underlying PFOS-induced hepatic glucolipid metabolic disorders remains elusive. The transcription factor forkhead box protein O 1 (FOXO1) plays a crucial role in regulating hepatic glucolipid metabolism; however, its involvement in PFOS-induced hepatic glucolipid metabolic disorders has not been thoroughly explored. Molecular docking revealed high binding affinity between PFOS and FOXO1. Male C57BL/6 mice were exposed to PFOS at doses of 0.3, 1.0, and 3.0 mg/kg body weight for 12 weeks to assess its subchronic effects on hepatic glucolipid metabolism in this work. The results indicate that PFOS exposure increases hepatic acetylated FOXO1 expression, promotes liver lipid accumulation, suppresses gluconeogenesis, whereas fasting blood glucose levels remain unaffected but this dysregulation results in insulin resistance. Furthermore, hepatic deletion of FOXO1 in PFOS-exposed mice ameliorates liver injury and reduces lipid accumulation by suppressing hepatic autophagy without significantly affecting gluconeogenesis. In conclusion, FOXO1 may play a pivotal role in the development of PFOS-induced hepatic glucolipid metabolic disorder.

The type VI secretion system (T6SS) is a specialized protein complex in Gram-negative bacteria that delivers toxic effector molecules into target cells. However, the role of ClpV-a critical ATPase involved in T6SS assembly in Salmonella pathogenesis remains poorly understood. In this study, we investigated the contribution of ClpV to environmental stress resistance and virulence in Salmonella enterica serovar Typhimurium (S. Typhimurium). Our findings demonstrate that ClpV significantly influences the ability of S. Typhimurium strain SL1344 to with stand various stressors, including bile salts, acidic conditions, hydrogen peroxide, and ethanol. Furthermore, ClpV enhances the competitive fitness of S. Typhimurium against commensal gut bacteria. Notably, ClpV appears to play a crucial role in pathogenicity by modulating the gut environment, disrupting microbial homeostasis, and facilitating bacterial persistence in host niches. These results provide a foundation for future studies on the molecular mechanisms by which T6SS mediates gut colonization and chronic infection in S. Typhimurium.

This study aims to explore how to deepen the construction of pharmacology course challenges based on the "golden course" standards and evaluate its application effects in improving course quality and students' comprehensive abilities. By integrating cutting-edge technologies with disciplinary knowledge, multidisciplinary teaching content was designed to promote curriculum innovation. A teaching method combining a three-tiered interactive model with case analysis was adopted to enhance student engagement in class. The study also incorporated virtual simulation experiments and innovative practices to further strengthen the integration of theory and practice, helping students better apply their knowledge to real-world scenarios. A comprehensive assessment of teaching effectiveness was conducted to scientifically measure students' learning outcomes and capability improvements. Through optimized instructional design, intensified skill training, enriched practical approaches, and balanced evaluation mechanisms, this study not only significantly enhanced course quality and student abilities but also provided valuable practical insights for the development of higher education.

HP568, an estrogen receptor (ER)-targeting proteolysis-targeting chimera (PROTAC) degraders that enhances the interaction between ER and an E3 ligase complex, resulting in ubiquitylation and subsequent proteasome mediated degradation. This compound exhibits high potency against both wild-type (half-maximal degradation concentration (DC50) < 1 nM) and ER mutants (DC50s < 5 nM), selectively inhibiting the proliferation of ER-dependent breast cancer cell lines in vitro. With an excellent ADME profile, it outperforms current ER-targeting PROTACs. In direct efficacy comparisons with ARV-471, HP568 shows superior, dose-dependent tumor growth inhibition (TGI) of 90%-123%, well correlated with drug exposure and pharmacodynamic biomarkers. Importantly, in models resistant to fulvestrant, including MCF-7 ERα D538G and Y537S cell-derived CDX mice, it demonstrates significant dose-dependent TGI (29%-115%) while maintaining favorable safety profiles. Moreover, HP568 demonstrates synergistic effects when combined with a CDK4/6 inhibitor. Secondary pharmacology and animal toxicity studies support its excellent safety and tolerability, together with the pharmacodynamic data, positioning it as a potential best-in-class ER-targeting degrader. The IND applications for HP568 have been approved by the China National Medical Products Administration and the U.S. FDA. An ongoing Phase 1/2 study (CTR20244203, NCT06757335) is currently being conducted in China for patients with ER+/HER2- advanced breast cancer. The Phase 1 dose escalation part of the study is assessing safety, pharmacokinetics, pharmacodynamics, preliminary antitumor activity, and potential efficacy biomarkers. The Phase 2 expansion will evaluate HP568 both as a monotherapy and in combination with a CDK4/6 inhibitor.HP568 structure will not be disclosed. Jing Li, Zhilin Tu, Luchan Deng, Zhipeng Quan, Wu Du, Xinghai Li. HP568, a highly potent and orally bioavailable ER PROTAC for breast cancer treatment, currently undergoing phase 1/2 clinical studies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr LB439.

Background: Diabetic nephropathy (DN) is a prevalent complication of diabetes mellitus and constitutes the primary cause of mortality in affected patients. Previous studies have shown that placental mesenchymal stem cells (PL-MSCs) can alleviate kidney dysfunction in animal models of DN. However, the limited ability of mesenchymal stem cells (MSCs) to home to damaged sites restricts their therapeutic potential. Enhancing the precision of PL-MSCs' homing to target tissues is therefore vital for the success of Methods: We developed Fe3O4 coated polydopamine nanoparticle (NP)-internalized MSCs and evaluated their therapeutic effectiveness in a mouse model of streptozotocin- and high-fat diet-induced DN, using an external magnetic field. Results: Our study confirmed that NPs were effectively internalized into PL-MSCs without compromising their intrinsic stem cell properties. The magnetic targeting of PL-MSCs notably improved their homing to the kidney tissues in mice with DN, resulting in enhanced kidney function compared to the transplantation of PL-MSCs alone. Furthermore, the anti-inflammatory and antifibrotic attributes of PL-MSCs played a role in the recovery of kidney function and structure. Conclusion: These results demonstrate that magnetically targeted therapy using PL-MSCs is a promising approach for treating diabetic nephropathy.

The genus Salmonella contains the most common foodborne pathogens frequently isolated from food-producing animals and is responsible for zoonotic infections in humans and animals. Salmonella infection in humans and animals can cause intestinal damage, resulting in intestinal inflammation and disruption of intestinal homeostasis more severe cases can lead to bacteremia. Pyroptosis, a proinflammatory form of programmed cell death, is involved in many disease processes. Inflammasomes, pyroptosis, along with their respective signaling cascades, are instrumental in the preservation of intestinal homeostasis. In recent years, with the in-depth study of pyroptosis, our comprehension of the virulence factors and effector proteins in Salmonella has reached an extensive level, a deficit persists in our knowledge regarding the intrinsic pathogenic mechanisms about pyroptosis, necessitating a continued pursuit of understanding and investigation. In this review, we discuss the occurrence of pyroptosis induced by Salmonella effectors to provide new ideas for elucidating the regulatory mechanisms through which Salmonella virulence factors and effector proteins trigger pyroptosis could pave the way for novel concepts and strategies in the clinical prevention of Salmonella infections and the treatment of associated diseases.

Salmonella enterica serovar Typhimurium (S. Typhimurium) is a common foodborne enteric pathogen that infects humans or mammals and colonizes the intestinal tract primarily by invading the host following ingestion. Meanwhile, ClpV is a core secreted protein of the bacterial type VI secretion system (T6SS). Because elucidating ClpV's role in the pathogenesis of T6SS is pivotal for revealing the virulence mechanism of Salmonella, in our study, clpV gene deletion mutants were constructed using a λ-red-based recombination system, and the effect of clpV mutation on SL1344's pathogenicity was examined in terms of stress resistance, motility, cytokine secretion, gut microbiota, and a BALB/c mouse model. Among the results, ClpV affected SL1344's motility and was also involved in cell invasion, adhesion, and intracellular survival in the MDBK cell model but did not affect invasion or intracellular survival in the RAW264.7 cell model. Moreover, clpV gene deletion significantly reduced the transcription levels of GBP2b, IFNB1, IL-6, NLRP3, NOS2, and TNF-α proinflammatory factor levels but significantly increased transcription levels of IL-4 and IL-10 anti-inflammatory factors. Last, ClpV appeared to closely relate to the pathogenicity of S. Typhimurium in vivo, which can change the gut environment and cause dysbiosis of gut microbiota. Our findings elucidate the functions of ClpV in S. Typhimurium and illustrating interactions between T6SS and gut microbiota help to clarify the mechanisms of the pathogenesis of foodborne diseases.

AimsTo explore the effect of plasma homocysteine (Hcy) on cardiometabolic multimorbidity (CMM) among Chinses adults.MethodsThis study combined a community-based cross-sectional study with a 1:1 matched case–control study using propensity score method among adults aged over 30 years in six districts randomly selected from Hunan Province, China. We recruited 5,258 people, of whom 4,012 met the study criteria were enrolled. CMM was defined as the coexistence of two or more cardiometabolic diseases, including diabetes, hypertension, coronary heart disease and stroke. The plasma Hcy and other laboratory data was measured by chemical automatic detector. Lifestyles and personal characteristics were collected by a questionnaire. Multivariate models were used to explore the associations. We calculated the attributable risk proportion (ARP) for the association of Hcy with CMM. The dose–response relationship was evaluated using restricted cubic splines method.ResultsOf the 4,012 adults, 436 had CMM, with a population prevalence of 10.9%. In the propensity-score-matched case–control study, 828 (414 cases and 414 controls) were included, and those with high plasma Hcy level (>16.2 μmol/L) had a higher risk of CMM than those with lowest level (<10.4 μmol/L) (adjusted OR = 2.83, 95% CI: 1.84–4.36, p < 0.001), with a multivariate ARP of high level of exposure was 64.66% (95% CI: 46.24–77.06%). The largest effect combination of CMM was the coexisting of diabetes, hypertension and coronary heart disease (adjusted OR = 2.26, 95%CI: 1.43–3.57, p < 0.001). An inverse association and dose–response relationship were observed between CMM and plasma Hcy levels. Notably, we recognized a significant mediation effect by C-reactive protein, total cholesterol, triglyceride and waist circumference, and they mediated approximately 8 ~ 23% of the effect of Hcy on risk of CMM.ConclusionOur findings add new evidence to this field that of high level of plasma Hcy was consistently associated with higher risk of CMM among Chinses adults, with the largest effect combination of being coexisting diabetes, hypertension and coronary heart disease. These findings have implications for cardiologists that CMM can be attributable to high level of plasma Hcy, and for decision makers that Hcy has become a public threat that persistently affects cardiovascular health in humans.

Safflower oil is easily oxidized; therefore, its oxidative stability can be improved using artificial oil bodies (AOBs). AOBs were assembled using safflower oil, phospholipids, and a conjugate comprising safflower caleosin (Ctcaleosin) and rosmarinic acid. AOBs coupled with rosmarinic acid exhibited better physical and thermal stability. The conjugate comprising safflower caleosin and rosmarinic acid was obtained by forming stable C-N covalent bonds. Circular dichroism spectroscopy analysis revealed that alpha-helix levels increased in safflower caleosin in the conjugate, which could be ascribed to the improvement in the stability and flexibility of safflower caleosin anchored by rosmarinic acid. Rosmarinic acid covering the surface of the AOBs and curcumin (Cur) located in the core of the artificial oil bodies significantly improved the physical and lipid oxidation stabilities of the artificial oil bodies. In vitro, release assay confirmed that curcumin in safflower caleosin-rosmarinic acid conjugate-modified AOBs loaded with curcumin (RAOBC) had a slower release efficiency than the free curcumin solution. The hemolysis assay confirmed the biological safety of RAOBC. The assembly of RAOBC can prevent the oxidation and deterioration of safflower oil, broadening its application in industry.

Ochratoxin A (OTA) is a significant global contaminant that poses severe challenges to food safety and public health. This study aims to isolate the OTA-degrated probiotics and evaluate genetic and biological characteristic. Here, The degradation rate of a new strain named Bacillus velezensis MM35 isolated from soil was the highest (87.10% within 48 h), and its culture supernatant was the main component of OTA degradation (63.95%) by high performance liquid chromatography. Further investigation revealed that the extracellular enzyme that degrades OTA in the culture supernatant of MM35 may be a small molecule enzyme with certain heat resistance. Genome-wide analysis showed that MM35 contains a cluster of carboxypeptidases encoding OTA-degrading potential, and had good metabolic and catalytic synthesis ability, and strong application potential in the synthesis and degradation of carbohydrates and proteins. A variety of secondary metabolites with antibacterial properties, such as non-ribosomal peptide synthetase and terpenoids, were identified in its metabolites. Consistent with the predicted results, MM35 showed various enzyme production characteristics such as cellulase and xylanase. Furthermore, MM35 could inhibit the growth of a variety of pathogenic bacteria, and showed high co-aggregation ability to Escherichia coli and Salmonella typhimurium. In addition, MM35 has certain tolerance to harsh environments such as strong acid, bile salt, and high temperature. Additionally, the adhesion rate of MM35 was 5.4%, and the invasion rate was 2.1% in IPEC-J2 cells. In summary, the data suggest MM35 isolated strain has high OTA degradation efficiency, antibacterial activity and intestinal colonization, which provided a new way for the treatment of OTA contamination in food and feed industries.

ABSTRACTThe causal relationship between visceral adipose tissue (VAT) and hypertension remains unclear. We aimed to examine the potential association between them using observational and two‐sample Mendelian randomization (MR) analyses. Data from the National Health and Nutrition Examination Survey (NHANES) 2011–2018 were used, applying multivariable logistic regression analysis to investigate the association between VAT mass and hypertension risk. Independent genetic variants related to VAT mass were derived from genome‐wide association studies (GWAS) in 325 153 UK Biobank participants. The primary analysis employed the random‐effects inverse‐variance weighted (IVW) method, with MR‐Egger, weighted median, simple mode, and weighted mode as sensitivity analyses. A total of 7661 participants were included. After adjusting for confounding factors, increased VAT mass was associated with a higher risk of hypertension (quartile 4 vs. quartile 1: OR:1.85, 95% confidence intervals [CI]: 1.31–2.63). Furthermore, VAT mass exhibited greater accuracy than body mass index (BMI) in predicting hypertension (areas under the curve [AUC]: 0.701 vs. 0.676, p for comparison < 0.001). The MR analyses demonstrated a causal relationship between increased VAT mass and the risk of hypertension in primary analyses (odds ratio [OR]:1.768, 95% CI: 1.594–1.861). Consistent findings across various MR models substantiate the robustness and strength of this causal relationship. These analyses provide additional support for both the positive association and causal relationship between elevated VAT and the risk of developing hypertension, suggesting that targeted interventions for VAT may be beneficial in preventing hypertension.

Acute kidney injury (AKI) is characterized by a sudden decline in renal function. The inflammatory response is the fundamental pathologic alteration throughout AKI, regardless of the various causal factors. Macrophages are the main immune cells involved in the inflammatory microenvironment in AKI. Consequently, targeting macrophages might become a novel strategy for the treatment of AKI. In this study, we demonstrated that pseudoginsenoside-F11 (PF11), a distinctive component of Panax quinquefolius L., regulated macrophage function and protected renal tubular epithelial cells TCMK-1 from lipopolysaccharide (LPS) in vitro. PF11 also alleviated renal injuries in an LPS-induced AKI mouse model, decreased the levels of inflammatory cytokines, reduced macrophage inflammatory infiltration, and promoted the polarization of M1 macrophages to M2c macrophages with suppression of the nuclear factor-κB/NOD-like receptor thermal protein domain-associated protein 3/interleukin-1β (NF-κB/NLRP3/IL-1β) signaling pathway. To further investigate whether this nephroprotective effect of PF11 is mediated by macrophages, we performed macrophage depletion by injection of clodronate liposomes in mice. Macrophage depletion abolished PF11's ability to protect against LPS-induced kidney damage with downregulating the NF-κB/NLRP3/IL-1β signaling pathway. In summary, this is the first study providing data on the efficacy and mechanism of PF11 in the treatment of AKI by regulating macrophage function.

Abstract Background Toll-like receptor 9 (TLR9) agonists are extensively studied for cancer treatment, but face challenges in delivery, clearance, and side effects. Our study showed that QTOLIMOD, a 26nt CpG-ODN delivered via QTsomeTM lipid nanoparticle, significantly inhibited tumor growth in MC38-bearing mice (TGI%=99.06%, p<0.001). Here, we report QTOLIMOD's potential for complete tumor rejection, prevention of recurrence, and advantages in safety and immune-cell induction. Methods C57BL/6 mice were subcutaneously inoculated with 1 × 106 MC38 cells. To assess drug tissue distribution, Cy5-labeled naked CpG-ODN or QTOLIMOD were intratumorally injected and in vivo imaging was conducted. ELISA was utilized to determine the levels of cytokines in serum and tumor samples. Once the tumor volume reached an average size of 80-100 mm3, mice were grouped and intratumorally injected with saline, vehicle, or QTOLIMOD. Tumor volume was calculated using the formula: length × width2 × 1/2. Results Following intratumoral injection of QTOLIMOD or naked CpG-ODN, free CpG-ODN were significantly reduced within 24 hours, while QTOLIMOD exhibited extended duration of action up to 7 days. Anatomical examination revealed that a dose of 5 mg/kg naked CpG-ODN caused liver and spleen enlargement in mice, whereas QTOLIMOD at the same dose did not cause the adverse events. Immunohistochemical assay indicated a significant increase in the infiltration of macrophages, dendritic cells, and CD8+ T cells at the tumor site after dosing. IL-10, IFN-γ, and IL-12 were significantly upregulated in the tumor samples, but not in the serum. In a dose escalation experiment, tumor suppression were observed with intratumoral injection of 0.5, 1, 1.5, or 2 mg/kg (every 3 days, 5 doses), resulting in tumor growth inhibition rates ranging from 92.5% to 98.8%. In the QTOLIMOD treated groups, complete tumor rejection was achieved in 4 out of 6 animals in the 0.5 mg/kg group and in all animals in the 1-2 mg/kg groups within 56 days. To investigate the effect of QTOLIMOD on tumor recurrence, cured mice were re-inoculated with MC38 tumor cells at a distant site. All cured mice rejected newly inoculated tumors without additional injection, resulting in 100% survival for up to 60 days. In a dosing frequency experiment, mice were administered with QTOLIMOD at 1 mg/kg once every 3, 5, 7, or 14 days for a total of 5 doses. The results suggested that fortnightly dosing of QTOLIMOD is more effective than more frequent dosing. Conclusions QTOLIMOD exhibits a high intratumoral retention rate, resulting in increased safety, while effectively promoting the expansion and infiltration of immune cells associated with tumors. Moreover, QTOLIMOD demonstrates potent efficacy in inhibiting tumor growth, potentially leading to complete eradication. Furthermore, treatment with QTOLIMOD effectively prevents tumor from recurrence, offering promising long-term effect. Citation Format: Fei Su, Jun Bai, Chen Li, Yujing Wu, Jing Li, Xiaobin Zhao, Yongsheng Yang, Robert J. Lee. QTOLIMOD: A specific TLR9 agonist nanomedicine with high anti-solid tumor activity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3251.