Enhancing cancer immunotherapy: Nanotechnology-mediated immunotherapy overcoming immunosuppression.

Immunotherapy is an important cancer treatment method that offers hope for curing cancer patients. While immunotherapy has achieved initial success, a major obstacle to its widespread adoption is the inability to benefit the majority of patients. The success or failure of immunotherapy is closely linked to the tumor's immune microenvironment. Recently, there has been significant attention on strategies to regulate the tumor immune microenvironment in order to stimulate anti-tumor immune responses in cancer immunotherapy. The distinctive physical properties and design flexibility of nanomedicines have been extensively utilized to target immune cells (including tumor-associated macrophages (TAMs), T cells, myeloid-derived suppressor cells (MDSCs), and tumor-associated fibroblasts (TAFs)), offering promising advancements in cancer immunotherapy. In this article, we have reviewed treatment strategies aimed at targeting various immune cells to regulate the tumor immune microenvironment. The focus is on cancer immunotherapy models that are based on nanomedicines, with the goal of inducing or enhancing anti-tumor immune responses to improve immunotherapy. It is worth noting that combining cancer immunotherapy with other treatments, such as chemotherapy, radiotherapy, and photodynamic therapy, can maximize the therapeutic effects. Finally, we have identified the challenges that nanotechnology-mediated immunotherapy needs to overcome in order to design more effective nanosystems.

Host genetics and gut microbiota synergistically regulate feed utilization in egg-type chickens.

BACKGROUND: Feed efficiency is a crucial economic trait in poultry industry. Both host genetics and gut microbiota influence feed efficiency. However, the associations between gut microbiota and host genetics, as well as their combined contributions to feed efficiency in laying hens during the late laying period, remain largely unclear. METHODS: In total, 686 laying hens were used for whole-genome resequencing and liver transcriptome sequencing. 16S rRNA gene sequencing was conducted on gut chyme (duodenum, jejunum, ileum, and cecum) and fecal samples from 705 individuals. Bioinformatic analysis was performed by integrating the genome, transcriptome, and microbiome to screen for key genetic variations, genes, and gut microbiota associated with feed efficiency. RESULTS: The heritability of feed conversion ratio (FCR) and residual feed intake (RFI) was determined to be 0.28 and 0.48, respectively. The ileal and fecal microbiota accounted for 15% and 10% of the FCR variance, while the jejunal, cecal, and fecal microbiota accounted for 20%, 11%, and 10% of the RFI variance. Through SMR analysis based on summary data from liver eQTL mapping and GWAS, we further identified four protein-coding genes, SUCLA2, TNFSF13B, SERTM1, and MARVELD3, that influence feed efficiency in laying hens. The SUCLA2 and TNFSF13B genes were significantly associated with SNP 1:25664581 and SNP rs312433097, respectively. SERTM1 showed significant associations with rs730958360 and 1:33542680 and is a potential causal gene associated with the abundance of Corynebacteriaceae in feces. MARVELD3 was significantly associated with the 1:135348198 and was significantly correlated with the abundance of Enterococcus in ileum. Specifically, a lower abundance of Enterococcus in ileum and a higher abundance of Corynebacteriaceae in feces were associated with better feed efficiency. CONCLUSIONS: This study confirms that both host genetics and gut microbiota can drive variations in feed efficiency. A small portion of the gut microbiota often interacts with host genes, collectively enhancing feed efficiency. Therefore, targeting both the gut microbiota and host genetic variation by supporting more efficient taxa and selective breeding could improve feed efficiency in laying hens during the late laying period.

The advance of ultrasound-enabled diagnostics and therapeutics.

Point-of-care ultrasound demonstrates significant potential in biomedical research due to its noninvasive, real-time visualization, cost-effectiveness, and other biological benefits. Ultrasound irradiation can precisely control the mechanical and physicochemical effects on pathogenic lesions, enabling real-time visualization, tunable tissue penetration depth, and therapeutic applications. This review summarizes recent advancements in ultrasound-enabled diagnostics and therapeutics, focusing on mechanochemical effects that can be directly integrated into biomedical applications. Additionally, the structure-functionality relationships of sonotheranostic nanoplatforms are systematically discussed, providing insights into the underlying biological effects. Finally, the limitations of current ultrasonic medicine are discussed, along with potential expansions to facilitate patient-centered translations.

Revolutionizing patient education with GPT-4o: A new approach to preventing surgical site infections in total hip arthroplasty.

Total hip arthroplasty (THA) is a common surgical procedure known for its generally positive outcomes, but it also comes with the risk of surgical site infections (SSIs), which can result in significant complications and higher healthcare costs. Effective patient education plays a vital role in reducing these risks, as well-informed patients are more likely to take preventive measures and identify early signs of complications. The advent of advanced language models like GPT-4o has opened new avenues for patient education, potentially revolutionizing the way information is delivered and understood. This research letter explores the utility of GPT-4o in enhancing patient education specifically related to SSIs following THA. The capabilities of GPT-4o include offering tailored educational materials, providing 24/7 availability, facilitating humanized interactive learning, and supporting multilingual education. These features significantly improve patient understanding, engagement, and adherence to preventive measures, enhancing the overall quality of healthcare services. However, challenges such as equitable access, language and cultural barriers, and data privacy must be addressed. Utilizing GPT-4o's advanced AI capabilities can revolutionize patient education, thereby decreasing the incidence of SSIs and enhancing postoperative recovery for THA patients.

Müller cells harboring exosomal lncRNA OGRU modulates microglia polarization in diabetic retinopathy via serving as miRNA sponges.

Diabetic retinopathy (DR) is one of the most common complications of diabetes mellitus which is associated with visual loss and blindness worldwide. However, the effective treatments for both early- and late-stage DR remains lacking. A streptozotocin (STZ)-induced diabetic mice model and high glucose (HG)-treated Müller cell model were established. M1/M2 microglia polarization was assessed by immunofluorescence (IF) staining and flow cytometry. Expression of lncRNA OGRU, cytokines and other key molecules were detected by qRT-PCR or western blot. ELISA assay was employed to monitor cytokine secretion. Müller cell-derived exosomes were isolated and characterized by nanopartical tracking analysis (NTA), western blot and transmission electron microscopy (TEM), and exosome uptake assay was used to monitor the intercellular transport of exosomes. Associations among lncRNA-miRNA-mRNA networks were validated by RNA pull-down and RNA immunoprecipitation (RIP) and dual luciferase assays. Increased M1 polarization but decreased M2 polarization of retinal microglia were observed in DR mice. HG-treated Müller cell-derived exosomes transported OGRU into microglia and promoted microglia polarization toward M1 phenotype. Mechanistically, OGRU served as a competing endogenous RNA (ceRNA) for miR-320-3p, miR-221-3p and miR-574-5p to regulate AR, PFKFB3 and GLUT1 expression in microglia, respectively. Loss of miR-320-3p/miR-221-3p/miR-574-5p or reinforced AR/PFKFB3/GLUT1 abrogated OGRU silencing-mediated microglia polarization in vitro. In vivo studies further showed that OGRU/miR-320-3p/AR, OGRU/miR-221-3p/PFKFB3 and OGRU/miR-574-5p/GLUT1 axes regulated microglia polarization in DR mice. Collectively, Müller cells-derived exosomal OGRU regulated microglia polarization in DR via modulating OGRU/miR-320-3p/AR, OGRU/miR-221-3p/PFKFB3 and OGRU/miR-574-5p/GLUT1 axes.

Dissecting the genetic basis of UV-B responsive metabolites in rice.

BACKGROUND: UV-B, an important environmental factor, has been shown to affect the yield and quality of rice (Oryza sativa) worldwide. However, the molecular mechanisms underlying the response to UV-B stress remain elusive in rice. RESULTS: We perform comprehensive metabolic profiling of leaves from 160 diverse rice accessions under UV-B and normal light conditions using a widely targeted metabolomics approach. Our results reveal substantial differences in metabolite accumulation between the two major rice subspecies indica and japonica, especially after UV-B treatment, implying the possible role and mechanism of metabolome changes in subspecies differentiation and the stress response. We next conduct a transcriptome analysis from four representative rice varieties under UV-B stress, revealing genes from amino acid and flavonoid pathways involved in the UV-B response. We further perform a metabolite-based genome-wide association study (mGWAS), which reveals 3307 distinct loci under UV-B stress. Identification and functional validation of candidate genes show that OsMYB44 regulates tryptamine accumulation to mediate UV-B tolerance, while OsUVR8 interacts with OsMYB110 to promote flavonoid accumulation and UV-B tolerance in a coordinated manner. Additionally, haplotype analysis suggests that natural variation of OsUVR8groupA contributes to UV-B resistance in rice. CONCLUSIONS: Our study reveals the complex biochemical and genetic foundations that govern the metabolite dynamics underlying the response, tolerance, and adaptive strategies of rice to UV-B stress. These findings provide new insights into the biochemical and genetic basis of the metabolome underlying the crop response, tolerance, and adaptation to UV-B stress.

Reynoutria multiflora (Thunb.) Moldenke and its ingredient suppress lethal prostate cancer growth by inducing CDC25B-CDK1 mediated cell cycle arrest.

BACKGROUND: Reynoutria multiflora (Thunb.) Moldenke (Polygonum multiflorum Thunb, PM) is a medicinal plant that was an element of traditional Chinese medicine (TCM) for centuries as a treatment for a wide range of conditions. Recent studies reported that PM suppressed prostate cancer growth in an AR-dependent manner. However, its role and mechanism in the treatment of advanced prostate cancer remain to be explored. This study aims to explore the anti-tumor role and potential mechanism of PM on prostate cancer. METHODS: Cell viability, colony formation, fluorescence-activated cell sorting (FACS), and wound-healing assays were conducted to evaluate the tumor suppression effect of PM on lethal prostate cancer models in vitro. A xenograft mice model was established to detect the impact of PM on tumor growth and evaluate its biosafety in vivo. Integrative network pharmacology, RNA-seq, and bioinformatics were applied to determine the mechanisms of PM in prostate cancer. Molecular docking, cellular thermal shift assay (CETSA), CRISPR-Cas13, RT-qPCR, and WB were collaboratively employed to identify the potential anti-tumor ingredient derived from PM and its corresponding targets. RESULTS: PM significantly suppressed the growth of prostate cancer and sensitized prostate cancer to AR antagonists. Mechanistically, PM induced G2/M-phase cell-cycle arrest by modulating the phosphorylation of CDK1. Additionally, polygalacic acid derived from PM and its structural analog suppress prostate cancer growth by targeting CDC25B, a master regulator of the cell cycle that governs CDK1 phosphorylation. CONCLUSION: PM and its ingredient polygalacic acid suppress lethal prostate cancer growth by regulating the CDC25B-CDK1 axis to induce cell cycle arrest.

Identification and Comprehensive Analysis of circRNA-miRNA-mRNA Regulatory Networks in A2780 Cells Treated with Resveratrol.

Ovarian cancer (OC) is one of the most commonplace gynecological malignancies. This study explored the effects of resveratrol (RES) on OC cell proliferation and apoptosis. Proliferation activity was measured for A2780 cells treated with RES for 24 h and 48 h at concentrations of 0, 10, 25, 50, 75, 100, 150, 200, and 300 µM. RNA sequencing (RNA-seq) was performed to analyze the circular RNA (circRNA), microRNA (miRNA), and messenger RNA (mRNA) expression spectrum. The differentially expressed genes included 460 circRNAs, 1988 miRNAs, and 1671 mRNAs, and they were subjected to analyses including Gene Ontology, the Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome enrichment. We selected signaling pathways enriched in the cell processes by mRNA KEGG, comprehensively analyzed the circRNA-miRNA-mRNA regulatory network, and verified several miRNAs expressed in the regulatory network diagram using the quantitative real-time polymerase chain reaction. The data showed that the cell proliferation of A2780 cells treated with RES for 24 h or 48 h decreased with increasing concentrations of RES. The circRNA-miRNA-mRNA regulatory network that we constructed provides new insights into the ability of RES to inhibit cell proliferation and promote apoptosis in A2780 cells.

Enhancing zinc biofortification and mitigating cadmium toxicity in soil-earthworm-spinach systems using different zinc sources.

Cadmium (Cd) pollution poses significant threats to soil organisms and human health by contaminating the food chain. This study aimed to assess the impact of various concentrations (50, 250, and 500 mg·kg-1) of zinc oxide nanoparticles (ZnO NPs), bulk ZnO, and ZnSO4 on morphological changes and toxic effects of Cd in the presence of earthworms and spinach. The results showed that Zn application markedly improved spinach growth parameters (such as fresh weight, plant height, root length, and root-specific surface area) and root morphology while significantly reducing Cd concentration and Cd bioconcentration factors (BCF-Cd) in spinach and earthworms, with ZnO NPs exhibiting the most pronounced effects. Earthworm, spinach root, and shoot Cd concentration decreased by 82.3 %, 77.0 %, and 75.6 %, respectively, compared to CK. Sequential-step extraction (BCR) analysis revealed a shift in soil Cd from stable to available forms, consistent with the available Cd (DTPA-Cd) results. All Zn treatments significantly reduced Cd accumulation, alleviated Cd-induced stress, and promoted spinach growth, with ZnO NPs demonstrating the highest Cd reduction and Zn bioaugmentation efficiencies compared to bulk ZnO and ZnSO4 at equivalent concentrations. Therefore, ZnO NPs offer a safer and more effective option for agricultural production and soil heavy metal pollution management than other Zn fertilizers.