Neutrophil Extracellular Traps in Breast Cancer: Roles in Metastasis and Beyond.

Despite advances in the treatment of breast cancer, the disease continues to exhibit high global morbidity and mortality. The importance of neutrophils in cancer development has been increasingly recognized. Neutrophil extracellular traps (NETs) are web-like structures released into the extracellular space by activated neutrophils, serving as a potential antimicrobial mechanism for capturing and eliminating microorganisms. The roles played by NETs in cancer development have been a subject of intense research in the last decade. In breast cancer, current evidence suggests that NETs are involved in various stages of cancer development, particularly during metastasis. In this review, we try to provide an updated overview of the roles played by NETs in breast cancer metastasis. These include: 1) facilitating systemic dissemination of cancer cells; 2) promoting cancer-associated inflammation; 3) facilitating cancer-associated thrombosis; 4) facilitating pre-metastatic niche formation; and 5) awakening dormant cancer cells. The translational implications of NETs in breast cancer treatment are also discussed. Understanding the relationship between NETs and breast cancer metastasis is expected to provide important insights for developing new therapeutic strategies for breast cancer patients.

The role of programmed cell death in osteosarcoma: From pathogenesis to therapy.

Osteosarcoma (OS) is a prevalent bone solid malignancy that primarily affects adolescents, particularly boys aged 14-19. This aggressive form of cancer often leads to deadly lung cancer due to its high migration ability. Experimental evidence suggests that programmed cell death (PCD) plays a crucial role in the development of osteosarcoma. Various forms of PCD, including apoptosis, ferroptosis, autophagy, necroptosis, and pyroptosis, contribute significantly to the progression of osteosarcoma. Additionally, different signaling pathways such as STAT3/c-Myc signal pathway, JNK signl pathway, PI3k/AKT/mTOR signal pathway, WNT/ß-catenin signal pathway, and RhoA signal pathway can influence the development of osteosarcoma by regulating PCD in osteosarcoma cell. Therefore, targeting PCD and the associated signaling pathways could offer a promising therapeutic approach for treating osteosarcoma.

Dysregulated Ribosome Biogenesis Is a Targetable Vulnerability in Triple-Negative Breast Cancer: MRPS27 as a Key Mediator of the Stemness-inhibitory Effect of Lovastatin.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with limited effective therapeutic options readily available. We have previously demonstrated that lovastatin, an FDA-approved lipid-lowering drug, selectively inhibits the stemness properties of TNBC. However, the intracellular targets of lovastatin in TNBC remain largely unknown. Here, we unexpectedly uncovered ribosome biogenesis as the predominant pathway targeted by lovastatin in TNBC. Lovastatin induced the translocation of ribosome biogenesis-related proteins including nucleophosmin (NPM), nucleolar and coiled-body phosphoprotein 1 (NOLC1), and the ribosomal protein RPL3. Lovastatin also suppressed the transcript levels of rRNAs and increased the nuclear protein level and transcriptional activity of p53, a master mediator of nucleolar stress. A prognostic model generated from 10 ribosome biogenesis-related genes showed outstanding performance in predicting the survival of TNBC patients. Mitochondrial ribosomal protein S27 (MRPS27), the top-ranked risky model gene, was highly expressed and correlated with tumor stage and lymph node involvement in TNBC. Mechanistically, MRPS27 knockdown inhibited the stemness properties and the malignant phenotypes of TNBC. Overexpression of MRPS27 attenuated the stemness-inhibitory effect of lovastatin in TNBC cells. Our findings reveal that dysregulated ribosome biogenesis is a targetable vulnerability and targeting MRPS27 could be a novel therapeutic strategy for TNBC patients.

Emerging therapeutic frontiers in cancer: insights into posttranslational modifications of PD-1/PD-L1 and regulatory pathways.

The interaction between programmed cell death ligand 1 (PD-L1), which is expressed on the surface of tumor cells, and programmed cell death 1 (PD-1), which is expressed on T cells, impedes the effective activation of tumor antigen-specific T cells, resulting in the evasion of tumor cells from immune-mediated killing. Blocking the PD-1/PD-L1 signaling pathway has been shown to be effective in preventing tumor immune evasion. PD-1/PD-L1 blocking antibodies have garnered significant attention in recent years within the field of tumor treatments, given the aforementioned mechanism. Furthermore, clinical research has substantiated the efficacy and safety of this immunotherapy across various tumors, offering renewed optimism for patients. However, challenges persist in anti-PD-1/PD-L1 therapies, marked by limited indications and the emergence of drug resistance. Consequently, identifying additional regulatory pathways and molecules associated with PD-1/PD-L1 and implementing judicious combined treatments are imperative for addressing the intricacies of tumor immune mechanisms. This review briefly outlines the structure of the PD-1/PD-L1 molecule, emphasizing the posttranslational modification regulatory mechanisms and related targets. Additionally, a comprehensive overview on the clinical research landscape concerning PD-1/PD-L1 post-translational modifications combined with PD-1/PD-L1 blocking antibodies to enhance outcomes for a broader spectrum of patients is presented based on foundational research.

Genome-Wide Analysis of the LBD Gene Family in Melon and Expression Analysis in Response to Wilt Disease Infection.

LBD transcription factors are a class of transcription factors that regulate the formation of lateral organs, establish boundaries, and control secondary metabolism in plants. In this study, we identified 37 melon LBD transcription factors using bioinformatics methods and analyzed their basic information, chromosomal location, collinearity, evolutionary tree, gene structure, and expression patterns. The results showed that the genes were unevenly distributed across the 13 chromosomes of melon plants, with tandem repeats appearing on chromosomes 11 and 12. These 37 transcription factors can be divided into two major categories, Class I and Class II, and seven subfamilies: Ia, Ib, Ic, Id, Ie, IIa, and IIb. Of the 37 included transcription factors, 25 genes each contained between one to three introns, while the other 12 genes did not contain introns. Through cis-acting element analysis, we identified response elements such as salicylic acid, MeJA, abscisic acid, and auxin, gibberellic acid, as well as light response, stress response, and MYB-specific binding sites. Expression pattern analysis showed that genes in the IIb subfamilies play important roles in the growth and development of various organs in melon plants. Expression analysis found that the majority of melon LBD genes were significantly upregulated after infection with wilt disease, with the strongest response observed in the stem.

Rapid mechanochemical synthesis of high-performance Na4Fe2.94Al0.04(PO4)2(P2O7)/C cathode material for sodium-ion storage.

Na4Fe3(PO4)2(P2O7) is regarded as a promising cathode material for sodium-ion batteries due to its affordability, non-toxic nature, and excellent structural stability. However, its electrochemical performance is hampered by its poor electronic conductivity. Meanwhile, most of the previous studies utilized spray-drying and sol-gel methods to synthesize Na4Fe3(PO4)2(P2O7), and the large-scale synthesis of the cathode material is still challenging. This study presents a composite cathode material, Na4Fe2.94Al0.04(PO4)2(P2O7)/C, prepared via a straightforward ball-milling technique. By substituting Al3+ minimally into the Fe2+ site of NFPP, Fe defects are introduced into the structure, hindering the formation of NaFePO4 and thereby enhancing Na-ion diffusion kinetics and conductivity. Additionally, the average length of AlO bonds (2.18 Å) is slightly smaller than that of FeO bonds (2.19 Å), contributing to the superior structural stability. The smaller ionic radii of Al3+ induce lattice contraction, further enhancing the structural stability. Moreover, the surface of material particles is coated with a thin layer of carbon, ensuring excellent electrical conductivity and outstanding structure stability. As a result, the Na4Fe2.94Al0.04(PO4)2(P2O7)/C cathode exhibits excellent electrochemical performance, leading to high discharge capacity (128.1 mAh g-1 at 0.2 C), outstanding rate performance (98.1 mAh g-1 at 10 C), and long cycle stability (83.7 % capacity retention after 3000 cycles at 10 C). This study demonstrates a low-cost, ultra-stable, and high-rate cathode material prepared by simple mechanical activation for sodium-ion batteries which has application prospects for large-scale production.

Nanomaterials Boost CAR-T Therapy for Solid Tumors.

T cell engineering, particularly via chimeric antigen receptor (CAR) modifications for enhancing tumor specificity, has shown efficacy in treating hematologic malignancies. The extension of CAR-T cell therapy to solid tumors, however, is impeded by several challenges: The absence of tumor-specific antigens, antigen heterogeneity, a complex immunosuppressive tumor microenvironment, and physical barriers to cell infiltration. Additionally, limitations in CAR-T cell manufacturing capacity and the high costs associated with these therapies restrict their widespread application. The integration of nanomaterials into CAR-T cell production and application offers a promising avenue to mitigate these challenges. Utilizing nanomaterials in the production of CAR-T cells can decrease product variability and lower production expenses, positively impacting the targeting and persistence of CAR-T cells in treatment and minimizing adverse effects. This review comprehensively evaluates the use of various nanomaterials in the production of CAR-T cells, genetic modification, and in vivo delivery. It discusses their underlying mechanisms and potential for clinical application, with a focus on improving specificity and safety in CAR-T cell therapy.

Disulfidptosis: Six Riddles Necessitating Solutions.

Disulfidptosis occurs as a result of the accumulation of intracellular cystine followed by disulfide stress in actin cytoskeleton proteins due to a reduction of NADPH produced through the pentose phosphate pathway in cells with high expression of SLC7A11. It is a cell death caused by the redox imbalance resulting from the disruption of amino acid metabolism and glucose metabolism. The discovery of disulfidptosis has sparked immense enthusiasm, but there are numerous unresolved issues that need to be addressed. Solutions to these riddles will provide insights into the detailed mechanisms and the pathophysiological relevance of disulfidptosis and utilizing disulfidptosis as an actionable therapeutic target.

Unleashing the power of immune checkpoints: Post-translational modification of novel molecules and clinical applications.

Immune checkpoint molecules play a pivotal role in the initiation, regulation, and termination of immune responses. Tumor cells exploit these checkpoints to dampen immune cell function, facilitating immune evasion. Clinical interventions target this mechanism by obstructing the binding of immune checkpoints to their ligands, thereby restoring the anti-tumor capabilities of immune cells. Notably, therapies centered on immune checkpoint inhibitors, particularly PD-1/PD-L1 and CTLA-4 blocking antibodies, have demonstrated significant clinical promise. However, a considerable portion of patients still encounter suboptimal efficacy and develop resistance. Recent years have witnessed an exponential surge in preclinical and clinical trials investigating novel immune checkpoint molecules such as TIM3, LAG3, TIGIT, NKG2D, and CD47, along with their respective ligands. The processes governing immune checkpoint molecules, from their synthesis to transmembrane deployment, interaction with ligands, and eventual degradation, are intricately tied to post-translational modifications. These modifications encompass glycosylation, phosphorylation, ubiquitination, neddylation, SUMOylation, palmitoylation, and ectodomain shedding. This discussion proceeds to provide a concise overview of the structural characteristics of several novel immune checkpoints and their ligands. Additionally, it outlines the regulatory mechanisms governed by post-translational modifications, offering insights into their potential clinical applications in immune checkpoint blockade.

Effects of simulated acid rain on hydrochemical factors and microbial community structure in red soil aquifers.

Acid rain can lower the pH of groundwater and affect its hydrogeochemistry and microbial ecology. However, the effects of acid rain on the hydrogeochemistry and microbial ecology of red soil groundwater systems in southern China are poorly understood. Previous research had mainly investigated the sources and patterns of groundwater acidification, but not the microbial mechanisms that contribute to this process and their associations with hydrochemical factors. To address this knowledge gap, we conducted a soil column experiment to simulate the infiltration of acid rain through various filter materials (coarse, medium, and fine sand) and to examine the hydrochemical and microbial features of the infiltrate, which can reveal how simulated acid rain (pH 3.5-7.0) alters the hydrochemistry and microbial community composition in red soil aquifers. The results showed that the pH of the leachate decreased due to simulated acid rain, and that the leaching efficiency of nitrogen and metal ions was influenced by the particle size of the filter media. Illumina 16S rRNA gene sequencing revealed that the leachate was dominated by Proteobacteria, Patescibacteria, Actinobacteria, and Acidobacteria, with Proteobacteria accounting for 67.04-74.69% of the bacterial community and containing a high proportion of nitrifying and denitrifying bacteria. Additionally, several genera with heavy metal tolerance, such as Burkholderia-Caballeronia-Paraburkholderia, Delftia, Methylversatilis, Aquicella, and Ralstonia, were widely distributed in the leachate, indicating the strong adaptive capacity of the microbial population. A correlation analysis between the hydrochemical factors and the microbial community structure revealed that pH was the most influential factor, followed by NO2--N, Fe, Al, Cu, Mn, and others. These results indicate that acidification modifies the hydrochemical conditions of the aquifer, creating an environment that is unfavorable for microbial growth and survival. However, some microorganisms may acquire resistance genes to cope with environmental changes.

In Situ Infrared Spectroscopic Evidence of Enhanced Electrochemical CO2 Reduction and C-C Coupling on Oxide-Derived Copper.

The reaction mechanism of CO2 electroreduction on oxide-derived copper has not yet been unraveled even though high C2+ Faradaic efficiencies are commonly observed on these surfaces. In this study, we aim to explore the effects of copper anodization on the adsorption of various CO2RR intermediates using in situ surface-enhanced infrared absorption spectroscopy (SEIRAS) on metallic and mildly anodized copper thin films. The in situ SEIRAS results show that the preoxidation process can significantly improve the overall CO2 reduction activity by (1) enhancing CO2 activation, (2) increasing CO uptake, and (3) promoting C-C coupling. First, the strong *COO- redshift indicates that the preoxidation process significantly enhances the first elementary step of CO2 adsorption and activation. The rapid uptake of adsorbed *COatop also illustrates how a high *CO coverage can be achieved in oxide-derived copper electrocatalysts. Finally, for the first time, we observed the formation of the *COCHO dimer on the anodized copper thin film. Using DFT calculations, we show how the presence of subsurface oxygen within the Cu lattice can improve the thermodynamics of C2 product formation via the coupling of adsorbed *CO and *CHO intermediates. This study advances our understanding of the role of surface and subsurface conditions in improving the catalytic reaction kinetics and product selectivity of CO2 reduction.

Sustainable synthesis of Ni, Mn co-doped FePO4@C cathode material for Na-ion batteries.

Olivine FePO4 is widely regarded as an optimal cathode material for sodium-ion batteries due to its impressive theoretical capacity of 177.7 mAh g-1. Nonetheless, the material's limited application stems from its intrinsic low electronic and ionic conductivities and ion diffusion rate. Previously, most modifications of olivine FePO4 are conducted through electrochemical or ion exchange processes in organic solvents, which severely restricted its potential for large-scale applications. In this research, a novel water-based ion exchange method is proposed for the synthesis of Ni-doped, Mn-doped, and Ni, Mn co-doped FePO4@C, which is non-toxic, cost-effective, and demonstrating promising prospects for various applications. Fe2.7Mn0.2Ni0.1PO4@C (0.2Mn0.1Ni-FP@C) is synthesized by a straightforward ion exchange method in aqueous media. The material exhibits a discharge capacity of 154.4 mAh g-1 at 0.1C rate. After 300 cycles at 1C, the capacity retention rate remains at 70.7 %. Numerous tests and calculations conducted in this study demonstrate that 0.2Mn0.1Ni-FP@C, modified through Mn3+ and Ni3+ co-doping, exhibits superior electrochemical performance due to its enhanced electronic conductivity and ion diffusion rate.

Amino acids and their roles in tumor immunotherapy of breast cancer.

Breast cancer is the most commonly diagnosed cancer among women. The primary treatment options include surgery, radiotherapy, chemotherapy, targeted therapy and hormone therapy. The effectiveness of breast cancer therapy varies depending on the stage and aggressiveness of the cancer, as well as individual factors. Advances in early detection and improved treatments have significantly increased survival rates for breast cancer patients. Nevertheless, specific subtypes of breast cancer, particularly triple-negative breast cancer, still lack effective treatment strategies. Thus, novel and effective therapeutic targets for breast cancer need to be explored. As substrates of protein synthesis, amino acids are important sources of energy and nutrition, only secondly to glucose. The rich supply of amino acids enables the tumor to maintain its proliferative competence through participation in energy generation, nucleoside synthesis and maintenance of cellular redox balance. Amino acids also play an important role in immune-suppressive microenvironment formation. Thus, the biological effects of amino acids may change unexpectedly in tumor-specific or oncogene-dependent manners. In recent years, there has been significant progress in the study of amino acid metabolism, particularly in their potential application as therapeutic targets in breast cancer. In this review, we provide an update on amino acid metabolism and discuss the therapeutic implications of amino acids in breast cancer.

Urinary stem cell-derived exocrine circRNA ATG7 regulates the SOCS1/STAT3 signaling pathway through miR-4500, inhibits M1 macrophage polarization, and alleviates the progression of diabetes nephropathy.

OBJECTIVE: The etiopathogenesis of diabetes nephropathy (DN) has not yet been fully clarified. Finding effective treatments to prevent renal failure in DN patients has become the main focus of research in recent years. Circular RNA (circRNA) has been shown to play a momentous role in DN progression. Based on this, we aimed to investigate the potential mechanism by which urine-derived stem cell (USC)-derived exosome circRNA ATG7 (Exo-ATG7) mediates DN progression. METHODS: Exosomes from USCs were isolated and identified. The DN rat model was established by intraperitoneally injecting 60 mg/kg streptozotocin. The protein expression levels were measured by Western blot and immunofluorescence. HE and Masson staining were used to evaluate renal injury, and the expression of related genes was detected by RT-qPCR. RESULTS: CircRNA ATG7 was significantly downregulated in the DN rat model, and the extracellular vesicles of USCs improved renal function and reduced inflammation in DN rats. However, after knocking down the USCs-derived exosome circRNA ATG7, improvement and therapeutic effect on renal function in DN rats were lost. In addition, overexpression of ATG7 facilitated the switching of macrophages from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype both in vivo and in vitro. Mechanistically, upregulation of circRNA ATG7 expression can alleviate renal damage in DN rats. Importantly, the USCs-derived exosome circRNA ATG7 promotes macrophage M2 polarization by regulating the SOCS1/STAT3 signaling pathway through miR-4500. In addition, animal experiments also confirmed that after knocking down ATG7 in USC cells, the extracted exosome-treated DN rats could weaken the therapeutic effect of USC exosomes. CONCLUSION: Our research results indicate that USC-derived exosomal circRNA ATG7 facilitates macrophage phenotype switching from M1 to M2 through the SOCS1/STAT3 signaling pathway mediated by miR-4500, thereby inhibiting DN progression.

The Influence of Physical Exercise on College Students’ Mental Health from The Perspective of Political Education / La influencia del ejercicio físico en la salud mental de los estudiantes universitarios desde la perspectiva de la educación política

This study examines the impact of parental support and course teachers on students' physical exercise behavior. It aims to provide insights for improving the physical education curriculum and enhancing its effectiveness. The purpose of using a Political education perspective in guiding physical education in colleges and universities is to assess the influence of physical education on college students' mental health and provide relevant information for physical education programs in these institutions. A random sampling method was used to survey 1000 college students in A City. The mental health of college students was assessed using the List 90 (SCL-90) developed by L.R. Derogatis, and their physical performance was evaluated using the Physical Performance Test (par-3) conducted by Liang Deqing and colleagues. The results were analysed. Statistically significant differences were found between the experimental and control groups in compulsion, interpersonal relationships, depression, hostility, fear, disorder, and emotion. Physical exercise showed a strong correlation of 91.7% with college students' mental health. By analysing the disparities, it is evident that various forms of physical education exert distinct impacts on mental well-being. The Political education perspective positively influences the guidance of college students' physical exercise. Regular physical exercise significantly benefits the overall health of college students, with a notable emphasis on its positive impact on their mental well-being. Firstly, broaden the scope of the study population and enhance the diversity of the research sample. While there is a substantial body of research on exercise behaviour among college students and adults, there is a scarcity of studies focusing on exercise behaviour among middle school children, particularly in the middle school age group. This study will contribute to the research field of exercise behaviour and expand the research group's scope. Secondly, interdisciplinary research. Physical exercise behaviour is a concern in both physical education and sociology. Children's mental health issues involve multiple disciplines, including psychology, sociology, economics, and demographics. Combining the two requires interdisciplinary knowledge to explain mechanisms and influencing factors comprehensively and reasonably.(AU)

Cancer chemoprevention with PV-1, a novel Prunella vulgaris-containing herbal mixture that remodels the tumor immune microenvironment in mice.

The herb Prunella vulgaris has shown significant immune-stimulatory and anti-inflammatory effects in mouse models. Here, the effects of a novel Prunella vulgaris-containing herbal mixture, PV-1, were examined in several mouse models for cancer, including chemically induced models of lung and oral cancers as well as syngraft models for lung cancer and melanoma. PV-1, consisting of extracts from Prunella vulgaris, Polygonum bistorta, Sonchus brachyotus and Dictamnus dasycarpus, exhibited no toxicity in a dose escalation study in A/J mice. PV-1 significantly inhibited mouse lung tumor development induced by the lung carcinogens vinyl carbamate and benzo[a]pyrene. PV-1 also hindered the induction of oral squamous cell carcinomas in C57BL/6 mice caused by 4-nitroquinoline-1-oxide. Flow cytometry analysis showed that PV-1 increased the numbers of CD8+ tumor-infiltrating lymphocytes (TILs) and increased the production of granzyme B, TNF-α, and IFN-γ by CD8+ TILs. PV-1 also suppressed granulocytic myeloid-derived suppressor cell numbers (g-MDSCs) and improved the anti-cancer activity of anti-PD-1 immunotherapy. These results indicate that PV-1 remodels the tumor immune microenvironment by selectively inhibiting g-MDSCs and increasing CD8+ TILs within tumors, resulting in decreased immune suppression and enhanced cancer chemopreventive efficacy.

Sub-3 nm Pt@Ru toward Outstanding Hydrogen Oxidation Reaction Performance in Alkaline Media.

Anion-exchange membrane fuel cells (AEMFCs) are promising alternative hydrogen conversion devices. However, the sluggish kinetics of the hydrogen oxidation reaction in alkaline media hinders further development of AEMFCs. As a synthesis method commonly used to prepare disordered PtRu alloys, the impregnation process is ingeniously designed herein to synthesize sub-3 nm Pt@Ru core-shell nanoparticles by sequentially reducing Pt and Ru at different annealing temperatures. This method avoids complex procedures and synthesis conditions for organic synthesis systems, and the atomic structure evolution of the synthesized core-shell nanoparticles can be tracked. The synthesized Pt@Ru electrocatalyst shows an ultrasmall average size of ∼2.5 nm and thereby a large electrochemical surface area (ECSA) of 166.66 m2 gPt+Ru-1. Exchange current densities (j0) normalized to the mass (Pt + Ru) and ECSA of this electrocatalyst are 8.0 and 5.8 times as high as those of commercial Pt/C, respectively. To the best of our knowledge, the achieved mass-normalized j0 measured by rotating disk electrodes is the highest reported so far. The membrane electrode assembly test of the Pt@Ru electrocatalyst shows a peak power density of 1.78 W cm-2 (0.152 mgPt+Ru cmanode-2), which is higher than that of commercial PtRu/C (1.62 W cm-2, 0.211 mgPt+Ru cmanode-2). The improvement of the intrinsic activity can be attributed to the electron transfer from the Ru shell to the Pt core, and the ultrafine particles further enhance the mass activity. This work reveals the feasibility of using simple impregnation to synthesize fine core-shell nanocatalysts and the importance of investigating the atomic structure of PtRu nanoparticles and other disordered alloys.

The Chemoprevention Effects of Two Herbal Mixtures on Chemically Induced Lung Tumorigenesis in Mice.

Ruan Hua Tang (RHT) and Ruan Hua Fang (RHF) are two Chinese herbal mixtures that have been used in clinical cancer treatment for decades. This study validated our hypothesis that RHT and RHF can inhibit lung tumor development in the mouse model of Benzo(a)pyrene-induced lung tumorigenesis. An RHT oral solution was diluted to 9% and 18% in water. RHF was mixed into the diet at 15% and 30% of total food in the final doses. Two weeks after injecting BP into mice, we administered RHT and RHF for eighteen weeks. We found that 9% and 18% RHT reduced tumor multiplicity by 36.05% and 38.81% (both p < 0.05) and the tumor load by 27.13% and 55.94% (p < 0.05); 15% and 30% RHF inhibited tumor multiplicity by 12.75% and 39.84% (p < 0.01) and the tumor load by 18.38% and 61.68% (p < 0.05). Ki67 expressions in the 9% and 18% RHT groups were 19.55% and 11.51%, significantly lower than in the control (33.64%). The Ki67 levels in the 15% and 30% RHF groups were 15.56% and 14.04%, significantly lower than in the control (27.86%). Caspase 3 expressions in the 9% and 18% RHT groups were 5.24% and 7.32%, significantly higher than in the control (2.39%). Caspase 3 levels in the 15% and 30% RHF groups were 6.53% and 4.74%, significantly higher than in the control (2.07%). The bio-absorption was confirmed via a pharmacokinetic test. This study showed that RHT and RHF are safe and can inhibit lung tumor development, with anti-proliferative and pro-apoptotic effects.

Molecular Characterization and Establishment of a Prognostic Model Based on Primary Immunodeficiency Features in Association with RNA Modifications in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. Although immunotherapy is effective for some patients, most find it difficult to benefit from it. This study aims to explore the impact of specific immune pathways and their regulated molecular mechanisms in TNBC. The gene expression data of breast cancer patients were obtained from the TCGA and METABRIC databases. Gene set variation analysis (GSVA) revealed specific upregulation or abnormal expression of immunodeficiency pathways in TNBC patients. Multi-omics data showed significant differential expression of Primary Immunodeficiency Genes (PIDGs) in TNBC patients, who are prone to genomic-level variations. Consensus clustering was used in two datasets to classify patients into two distinct molecular subtypes based on PIDGs expression patterns, with each displaying different biological features and immune landscapes. To further explore the prognostic characteristics of PIDGs-regulated molecules, we constructed a four-gene prognostic PIDG score model and a nomogram using least absolute shrinkage and selection operator (LASSO) regression analysis in combination with clinicopathological parameters. The PIDG score was closely associated with the immune therapy and drug sensitivity of TNBC patients, providing potential guidance for clinical treatment. Particularly noteworthy is the close association of this scoring with RNA modifications; patients with different scores also exhibited different mutation landscapes. This study offers new insights for the clinical treatment of TNBC and for identifying novel prognostic markers and therapeutic targets in TNBC.