A self-powered theranostic DNA nanodevice for amplification of both intracellular microRNA imaging and photodynamic therapy.

While numerous methods exist for diagnosing tumors through the detection of miRNA within tumor cells, few can simultaneously achieve both tumor diagnosis and treatment. In this study, a novel graphene oxide (GO)-based DNA nanodevice (DND), initiated by miRNA, was developed for fluorescence signal amplification imaging and photodynamic therapy in tumor cells. After entering the cells, tumor-associated miRNA drives DND to Catalyzed hairpin self-assembly (CHA). The CHA reaction generated a multitude of DNA Y-type structures, resulting in a substantial amplification of Ce6 fluorescence release and the generation of numerous singlet oxygen (1O2) species induced by laser irradiation, consequently inducing cell apoptosis. In solution, DND exhibited high selectivity and sensitivity to miRNA-21, with a detection limit of 11.47 pM. Furthermore, DND discriminated between normal and tumor cells via fluorescence imaging and specifically generated O21 species in tumor cells upon laser irradiation, resulting in tumor cells apoptosis. The DND offer a new approach for the early diagnosis and timely treatment of malignant tumors.

Coupled iron and heavy metal accumulation in karst soils in Southwestern China: Iron isotope perspective.

Heavy metals (HMs) are abundant in the karst soils of Southwest China, posing significant health risks to millions of people. Iron (Fe) (hyr)oxides serve as critical carriers of HMs in these soils; however, the processes governing Fe oxide formation and transformation associated with HM accumulation during carbonate weathering in karst region is less understood. In this study, we present Fe isotope compositions from a carbonate-derived profile to investigate the major factors controlling Fe migration. In the saprolite layer, strong correlations between δ56Febulk and the proportions of extracted FeNH2OH.HCl or Feresidue fractions suggest that the formation of goethite and phyllosilicate may be responsible for variations in δ56Febulk. The positive correlations between δ56FeNH2OH.HCl values and HM concentrations in this layer suggest an enhanced capacity for HM fixation by goethite in these soils. In contrast, the fractionation of Fe isotopes in the soil layer appears to be influenced by vegetation, as indicated by the correlation between total organic carbon and δ56Febulk. The negative correlations between δ56Febulk values and HM concentrations in the soil layer likely indicate that vegetation litter enhances the retention capacity of Fe oxides for HMs. This study highlights the trajectory of Fe and its connection to HM accumulation in karst soil with high geological background levels.

The effect of total thyroidectomy and radioactive iodine on long-term survival in unilateral T3/T4 follicular thyroid carcinoma: insights from a propensity-matched retrospective analysis.

Background: Follicular thyroid carcinoma (FTC) is the second most common thyroid malignancy and is particularly aggressive in advanced stages such as T3 and T4. This retrospective study aimed to evaluate the long-term survival outcomes of total thyroidectomy (TT) and radioactive iodine therapy (RAIT) in unilateral T3 or T4 FTC using propensity score-matched analysis. Methods: Utilizing the Surveillance, Epidemiology, and End Results (SEER) database, we identified patients diagnosed with T3 or T4 FTC and categorized them into two cohorts, namely those who were treated with TT and those who were not (non-TT). The non-TT group was further analyzed to determine the impact of RAIT on survival. Propensity score matching (PSM) was applied to adjust for confounding variables. Survival analysis, including Kaplan-Meier survival curves and landmark analysis, evaluated the effects on overall survival (OS) and cancer-specific survival (CSS). Results: A total of 2,957 patients were included, with 2,271 (76.8%) undergoing TT and 686 (23.2%) receiving alternative treatments. Before and after PSM, there were no significant differences in OS and CSS between the two groups. Post-PSM landmark analysis revealed that beyond 90 months, the TT group had superior CSS compared with the non-TT group (P=0.06). Cox multivariate regression identified follicular adenocarcinoma trabecular [hazard ratio (HR) =4.7041; 95% confidence interval (CI): 1.1218-19.727] and minimally invasive follicular carcinoma (HR =2.0202; 95% CI: 1.2140-3.362) as independent risk factors affecting prognosis. In the second part of the study, 671 patients were analyzed, namely 197 (29.4%) who received RAIT and 474 (70.6%) who did not. Landmark analysis indicated that after 30 months, the RAIT group had superior CSS compared with the non-RAIT group (P<0.05). Conclusions: TT does not improve the survival rates of patients with stage T3/T4 FTC. For those patients who have not undergone TT, RAIT proves beneficial for CSS; however, further in-depth studies are required.

[Daidzein attenuates high glucose-induced inflammatory injury in macrophages by regulating NLRP3 inflammasome signaling pathway].

This study aims to explore the inhibitory effect of daidzein on macrophage inflammation induced by high glucose via regulating the NOD-like receptor protein 3(NLRP3) inflammasome signaling pathway. The cell counting kit-8(CCK-8) assay was employed to detect the effects of daidzein at different concentrations on the viability of RAW264.7 cells. Western blot was employed to determine the protein level of tumor necrosis factor(TNF)-α in macrophages exposed to different concentrations of glucose for different time periods as well as the expression levels of proteins involved in the polarization and Toll-like receptor 4(TLR4)-myeloid differentiation factor(MyD88)-NLRP3 inflammasome pathway of the macrophages exposed to high glucose. Enzyme-linked immunosorbent assay was employed to measure the levels of TNF-α, interleukin(IL)-18, and IL-1ß secreted by macrophages. The expression level of nuclear factor-kappa B(NF-κB) p65 in macrophages exposed to high glucose was detected by immunofluorescence, and the level of intracellular reactive oxygen species(ROS) was detected by the DCFH-DA fluorescent probe. The mRNA levels of NLRP3, TNF-α, and IL-18 in macrophages were determined by qRT-PCR. The results showed that treatment with 30 mmol·L~(-1) glucose for 48 h was the best condition for the modeling of macrophage injury. Compared with the blank group, the model group showed improved polarization of macrophages, increased secretion of TNF-α, IL-18, and IL-1ß, elevated ROS level, and up-regulated expression of NF-κB p65. In addition, the modeling up-regulated the mRNA levels of NLRP3, TNF-α, and IL-18 and the protein levels of TLR4, MyD88, NLRP3, NF-κB p65, p-NF-κB p65, I-κB, p-I-κB, ASC, pro-caspase-1, pro-IL-1ß, cleaved IL-1ß, and pro-IL-18. Compared with the model group, daidzein(10, 20, and 40 µmol·L~(-1)) lowered the levels of inflammatory cytokines and down-regulated the mRNA levels of NLRP3, TNF-α, and IL-18 as well as the protein levels of TLR4, MyD88, NLRP3, NF-κB p65, p-NF-κB p65, I-κB, p-I-κB, ASC, pro-caspase-1, pro-IL-1ß, cleaved IL-1ß, and pro-IL-18. In addition, daidzein reduced intracellular ROS. According to the available reports and the experimental results, high glucose can induce the polarization of macrophages and promote the secretion of inflammatory cytokines. Daidzein can inhibit the expression of ROS in macrophages by regulating the NLRP3 inflammasome signaling pathway, thereby reducing the inflammation of macrophages exposed to high glucose.

Puerarin ameliorates high glucose-induced MIN6 cell injury by activating PINK1/Parkin-mediated mitochondrial autophagy.

The dysfunction of pancreatic ß-cells plays a pivotal role in the pathogenesis of type 2 diabetes mellitus (T2DM). Despite numerous studies demonstrating the anti-inflammatory and antioxidant properties of puerarin, the protective effects of puerarin on ß-cells remain poorly understood. Hence, this study aimed to explore the effects of puerarin on ß-cell dysfunction in a hyperglycemic environment via the PINK/Parkin-mediated mitochondrial autophagy pathway. The alterations in cell viability of MIN6 cells exposed to glucose concentrations of 5 mM, 10 mM, 20 mM, and 30 mM for 24 h, 48 h, and 72 h, respectively, were assessed using the CCK-8 assay to optimize the modeling conditions. Subsequently, cellular insulin secretion was measured using enzyme-linked immunosorbent assay (ELISA), apoptosis rate by flow cytometry, mitochondrial membrane potential alteration by JC-1, cellular ROS production by the DCFH-DA fluorescent probe, and fusion of cellular autophagosomes and lysosomes through adenoviral infection analysis. Furthermore, gene and protein expression levels of the PINK/Parkin-mediated mitochondrial autophagy pathway and mitochondrial apoptosis pathway were assessed using real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot, respectively. Results indicated a significant decrease in MIN6 cell viability following 48 h of exposure to 30 mM glucose concentration. Puerarin intervention markedly attenuated ROS production, restored mitochondrial membrane potential, induced PINK/Parkin-mediated mitochondrial autophagy, suppressed activation of the mitochondrial apoptotic pathway, mitigated apoptosis, and enhanced insulin secretion in a high glucose (HG) environment. The findings of this investigation contribute to a deeper understanding of the precise mechanism underlying the protective effects of puerarin on ß-cells and offer a theoretical foundation for advancing puerarin-based therapeutics aimed at ameliorating T2DM.

Discovery of antitumor diterpenoids from Casearia graveolens targeting VEGFR-2 to inhibit angiogenesis.

Eight novel clerodane diterpenoids (1-8) were isolated from the twigs of Casearia graveolens. Their structures were elucidated through comprehensive nuclear magnetic resonance (NMR), high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), and electronic circular dichroism (ECD) analyses. In addition to structural determination, surface plasmon resonance (SPR) assays were conducted to investigate molecular interactions, revealing that compound 8 exhibited high affinity for vascular endothelial growth factor receptor 2 (VEGFR2), a key regulator of tumor angiogenesis. Subsequent in vivo experiments demonstrated that compound 8 effectively inhibited angiogenesis and displayed significant antitumor activity by suppressing tumor proliferation and metastasis in zebrafish xenograft models. These findings suggest that compound 8 holds promise as an anticancer lead compound targeting VEGFR-2 to obstruct tumor angiogenesis.

The Abscisic Acid Receptor Gene StPYL8-like from Solanum tuberosum Confers Tolerance to Drought Stress in Transgenic Plants.

Pyrabactin resistance 1-like (PYL) proteins are abscisic acid (ABA) receptors that play a crucial role in the plant's response to adverse environmental conditions. However, as of yet, there is limited research on the role of PYL proteins in potato. In this study, a potato PYL gene, StPYL8-like, was identified through transcriptome analysis under drought stress. Molecular characterization revealed that the StPYL8-like protein possesses a highly conserved PYL family domain. Evolutionary analysis demonstrated that StPYL8-like protein clusters with various PYL proteins are involved in stress responses across different species. Functional assays showed that StPYL8-like robustly responds to different abiotic stresses, including drought and ABA treatment. Furthermore, the transient and stable expressions of StPYL8-like in tobacco enhanced their drought resistance, leading to increased plant height, leaf number, and fresh weight, as well as an improved root system. Transgenic tobacco carrying the StPYL8-like gene exhibited lower malondialdehyde (MDA) levels and higher proline accumulation and antioxidant enzyme activity compared to wild-type plants under drought conditions. Moreover, StPYL8-like upregulated the expression of stress-responsive genes (NtRD29A, NtLEA5, NtP5CS, NtPOD, NtSOD, and NtCAT) in transgenic plants subjected to drought stress. Collectively, these findings highlight the positive regulatory role of the StPYL8-like gene in enhancing potato plants' response to drought stress.

Overexpression of Potato PYL16 Gene in Tobacco Enhances the Transgenic Plant Tolerance to Drought Stress.

PYR/PYL/RCAR proteins are abscisic acid (ABA) receptors that play a crucial role in plant responses to abiotic stresses. However, there have been no research reports on potato PYL so far. In this study, a potato PYL gene named StPYL16 was identified based on transcriptome data under drought stress. Molecular characteristics analysis revealed that the StPYL16 protein possesses an extremely conserved PYL family domain. The tissue expression results indicated that the StPYL16 is predominantly expressed at high levels in the underground parts, particularly in tubers. Abiotic stress response showed that StPYL16 has a significant response to drought treatment. Further research on the promoter showed that drought stress could enhance the activation activity of the StPYL16 promoter on the reporter gene. Then, transient and stable expression of StPYL16 in tobacco enhanced the drought resistance of transgenic plants, resulting in improved plant height, stem thickness, and root development. In addition, compared with wild-type plants, StPYL16 transgenic tobacco exhibited lower malondialdehyde (MDA) content, higher proline accumulation, and stronger superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) activities. Meanwhile, StPYL16 also up-regulated the expression levels of stress-related genes (NtSOD, NtCAT, NtPOD, NtRD29A, NtLEA5, and NtP5CS) in transgenic plants under drought treatment. These findings indicated that the StPYL16 gene plays a positive regulatory role in potato responses to drought stress.

Multifunctional Roles of Zinc in Cadmium Transport in Soil-Rice Systems: Novel Insights from Stable Isotope Fractionation and Gene Expression.

The effect of Zn on Cd accumulation in rice varies under flooding and drainage conditions, and the underlying mechanism during uptake and transport from the soil to grains remains unclear. Isotope fractionation and gene expression were investigated using pot experiments under distinct water regimes and with Zn addition to gain a deeper understanding of the molecular effects of Zn on Cd uptake and transport in rice. The higher OsHMA2 expression but constitutively lower expression of zinc-regulated, iron-regulated transporter-like protein (ZIP) family genes in roots under the drainage regime than the flooding regime caused the enrichment of nonheavy Zn isotopes in the shoots relative to roots but minimally affected Cd isotopic fractionation. Drainage regime seem to exert a striking effect on the root-to-shoot translocation of Zn rather than Cd, and increased Zn transport via OsHMA2. The changes in expression patterns in response to Zn addition were similar to those observed upon switching from the flooding to drainage regime, except for OsNRAMP1 and OsNRAMP5. However, soil solution-to-rice plants and root-to-shoot fractionation toward light Zn isotopes with Zn addition (Δ66Znrice plant-soil solution = -0.49 to -0.40‰, Δ66Znshoot-root = -0.36 to -0.27‰) indicated that Zn transport occurred via nonspecific uptake pathways and OsHMA2, respectively. Accordingly, the less pronounced and minimally varied Cd isotope fractionation suggested that OsNRAMP5 and OsHMA2 are crucial for Cd uptake and root-to-shoot transport, respectively, facilitating Cd accumulation in grains. This study demonstrated that a high Zn supply promotes Cd uptake and root-to-shoot transport in rice by sharing distinct pathways, and by utilizing a non-Zn-sensitive pathway with a high affinity for Cd.

MiR-200b-3p elevates 5-FU sensitivity in cholangiocarcinoma cells via autophagy inhibition by targeting KLF4.

Cholangiocarcinoma is one of the most lethal human cancers, and chemotherapy failure is a major cause of recurrence and poor prognosis. We previously demonstrated that miR-200 family members are downregulated in clinical samples of cholangiocarcinoma and inhibit cholangiocarcinoma tumorigenesis and metastasis. However, the role of differentially expressed miR-200b-3p in 5-fluorouracil chemosensitivity remains unclear. Here, we examined how miR-200b-3p modulates 5-fluorouracil chemosensitivity in cholangiocarcinoma. We observed that miR-200b-3p was associated with 5-fluorouracil sensitivity in cholangiocarcinoma and increased 5-fluorouracil-induced mitochondrial apoptosis in cholangiocarcinoma cells. Mechanistically, miR-200b-3p suppressed autophagy in cholangiocarcinoma cells to mediate 5-fluorouracil sensitivity. Further, we identified KLF4 as an essential target of miR-200b-3p in cholangiocarcinoma. Notably, the miR-200b-3p/KLF4/autophagy pathway augmented the chemosensitivity of cholangiocarcinoma cells to 5-fluorouracil. Our findings underscore the key role of miR-200b-3p in chemosensitivity to 5-fluorouracil and highlight the miR-200b-3p/KLF4/autophagy axis as a potential therapeutic target for cholangiocarcinoma.

Unlocking the potential of surface modification with phosphate on ball milled zero-valent iron reactivity:Implications for radioactive metal ions removal.

Numerous investigations have illuminated the profound impact of phosphate on the adsorption of uranium, however, the effect of phosphate-mediated surface modification on the reactivity of zero-valent iron (ZVI) remained enigmatic. In this study, a phosphate-modified ZVI (P-ZVIbm) was prepared with a facile ball milling strategy, and compared with ZVIbm, the U(VI) removal amount (435.2 mg/g) and efficiency (3.52×10-3 g·mg-1·min-1) of P-ZVIbm were disclosed nearly 2.0 and 54 times larger than those of ZVIbm respectively. The identification of products revealed that the adsorption mechanism dominated the removal process for ZVIbm, while the reactive modified layer strengthened both the adsorption pattern and reduction performance on P-ZVIbm. DFT calculation result demonstrated that the binding configuration shifted from bidentate binuclear to multidentate configuration, further shortening the Fe-U atomic distance. More importantly, the electron transferred is more accessible through the surface phosphate layer, and selectively donated to U(VI), accounting for the elevated reduction performance of P-ZVIbm. This investigation explicitly underscores the critical role of ZVI's surface microenvironment in the domain of radioactive metal ion mitigation and introduces a novel methodology to amplify the sequestration of U(VI) from aqueous environments.

Rejuvenation of peripheral immune cells attenuates Alzheimer's disease-like pathologies and behavioral deficits in a mouse model.

Immunosenescence contributes to systematic aging and plays a role in the pathogenesis of Alzheimer's disease (AD). Therefore, the objective of this study was to investigate the potential of immune rejuvenation as a therapeutic strategy for AD. To achieve this, the immune systems of aged APP/PS1 mice were rejuvenated through young bone marrow transplantation (BMT). Single-cell RNA sequencing revealed that young BMT restored the expression of aging- and AD-related genes in multiple cell types within blood immune cells. The level of circulating senescence-associated secretory phenotype proteins was decreased following young BMT. Notably, young BMT resulted in a significant reduction in cerebral Aß plaque burden, neuronal degeneration, neuroinflammation, and improvement of behavioral deficits in aged APP/PS1 mice. The ameliorated cerebral amyloidosis was associated with an enhanced Aß clearance of peripheral monocytes. In conclusion, our study provides evidence that immune system rejuvenation represents a promising therapeutic approach for AD.

A Red-Emission Fluorescent Probe with Large Stokes Shift for Detection of Viscosity in Living Cells and Tumor-Bearing Mice.

Abnormal viscosity is closely related to the occurrence of many diseases, such as cancer. Therefore, real-time detection of changes in viscosity in living cells is of great importance. Fluorescent molecular rotors play a critical role in detecting changes in cellular viscosity. Developing red emission viscosity probes with large Stokes shifts and high sensitivity and specificity remains an urgent and important topic. Herein, a novel viscosity-sensitive fluorescent probe (TCF-VIS1) with a large stokes shift and red emission was prepared based on the 2-dicyanomethylene-3-cyano-4,5,5-trimethyl-2,5-dihydrofuran (TCF) skeleton. Due to intramolecular rotation, the probe itself does not fluorescence at low viscosity. With the increase in viscosity, the rotation of TCF-VIS1 is limited, and its fluorescence is obviously enhanced. The probe has the advantages of simple preparation, large Stokes shift, good sensitivity and selectivity, and low cytotoxicity, which make it successfully used for viscosity detection in living cells. Moreover, TCF-VIS1 showed its potential for cancer diagnosis at the cell level and in tumor-bearing mice by detecting viscosity. Therefore, the probe is expected to enrich strategies for the detection of viscosity in biological systems and offer a potential tool for cancer diagnosis.

Clinical effects of atorvastatin combined with conbercept in the treatment of patients with macular edema secondary to retinal vein occlusion and carotid plaque: study protocol for a prospective randomized controlled trial.

INTRODUCTION: Intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) drugs have been widely used in patients with macular edema (ME) secondary to retinal vein occlusion (RVO); however, recurrence is a major concern. This study aims to observe the clinical effects of atorvastatin and intravitreal therapy in the treatment of patients with branch or central RVO-ME and coexistent carotid plaques (CP). METHODS AND ANALYSIS: A prospective randomized controlled clinical trial will be conducted. Sixty-four patients diagnosed with branch or central RVO-ME and coexistent CP will be enrolled and randomly allocated in a 1:1 ratio to the control and experimental groups. The control group will be treated with intravitreal conbercept monthly for 3 months, followed by monthly evaluation and injection of pro re nata (PRN) for 12 months, while the experimental group will be treated with oral atorvastatin 20 mg daily combined with the control group treatment. If a drop of best-corrected visual acuity (BCVA) is more than five Early Treatment Diabetic Retinopathy Study (ETDRS) letters (one line) or an increment in central subfield thickness (CSFT) of 100 µm (or a 10% increment from the previous visit), intravitreal re-treatment will be performed. Outcome measurements include CSFT, BCVA, number of injections, and incidence of adverse events during the 12-month follow-up period. Differences between groups will be evaluated using Student's t-test, and comparisons between groups will be evaluated using repeated-measures analysis of variance. ETHICS AND DISSEMINATION: The study has been approved by the Institutional Review Board of Nanjing Lishui People's Hospital, Nanjing, China (approval number 2023KY0418-12, dated 18 April 2023), and has been registered on chictr.org.cn. Written informed consent will be collected from each patient and the results of this trial will be submitted to a peer-reviewed journal. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300071359. Registered on 12 May 2023.

The Association of Circulating Glucagon-Like Peptide-1 with Cognitive Functions and Biomarkers in Alzheimer's Disease.

Background: Alzheimer's disease (AD) is an age-related neurodegenerative disease that is clinically characterized by progressive cognitive decline. Glucagon-like peptide-1 (GLP-1) is a hormone that belongs to the incretin family and is released in response to nutrient intake. It plays a role in maintaining metabolic homeostasis and has been suggested to be involved in maintaining the brain microenvironment. However, the role of GLP-1 in AD pathogenesis has not been fully illustrated. Objective: This study aims to investigate the clinical relevance of GLP-1 in AD and the effects of GLP-1 in amyloid-ß (Aß) metabolism in vitro. Methods: In this study, 39 AD patients and 120 cognitively intact controls were included. Plasma levels of GLP-1 were measured using ELISA. SH-SY5Y cells overexpressing human amyloid precursor protein (APP) were treated with GLP-1. Western blot analysis was used to assess the effects of GLP-1 on the metabolism of Aß. Results: Plasma GLP-1 levels were decreased with aging. Plasma GLP-1 levels were lower in AD patients in comparison with healthy older adults. Plasma GLP-1 levels were positively associated with Mini-Mental State Examination scores but negatively associated with plasma pTau181 levels. GLP-1 dose-dependently increased the area fraction of mitochondrial staining in vitro. Furthermore, GLP-1 dose-dependently promoted the α-cleavage of APP, thus reducing the generation of Aß. Conclusions: GLP-1 has neuroprotective effects in AD, and therefore the decrease in GLP-1 levels during aging might contribute to the development of AD.

Proteomic analysis of DEN and CCl4-induced hepatocellular carcinoma mouse model.

Hepatocellular carcinoma (HCC) seriously threatens human health, mostly developed from liver fibrosis or cirrhosis. Since diethylnitrosamine (DEN) and carbon tetrachloride (CCl4)-induced HCC mouse model almost recapitulates the characteristic of HCC with fibrosis and inflammation, it is taken as an essential tool to investigate the pathogenesis of HCC. However, a comprehensive understanding of the protein expression profile of this model is little. In this study, we performed proteomic analysis of this model to elucidate its proteomic characteristics. Compared with normal liver tissues, 432 differentially expressed proteins (DEPs) were identified in tumor tissues, among which 365 were up-regulated and 67 were down-regulated. Through Gene Ontology (GO) analysis, Ingenuity Pathway Analysis (IPA), protein-protein interaction networks (PPI) analysis and Gene-set enrichment analysis (GSEA) analysis of DEPs, we identified two distinguishing features of DEN and CCl4-induced HCC mouse model in protein expression, the upregulation of actin cytoskeleton and branched-chain amino acids metabolic reprogramming. In addition, matching DEPs from the mouse model to homologous proteins in the human HCC cohort revealed that the DEN and CCl4-induced HCC mouse model was relatively similar to the subtype of HCC with poor prognosis. Finally, combining clinical information from the HCC cohort, we screened seven proteins with prognostic significance, SMAD2, PTPN1, PCNA, MTHFD1L, MBOAT7, FABP5, and AGRN. Overall, we provided proteomic data of the DEN and CCl4-induced HCC mouse model and highlighted the important proteins and pathways in it, contributing to the rational application of this model in HCC research.

A Cancer Nanovaccine Based on an FeAl-Layered Double Hydroxide Framework for Reactive Oxygen Species-Augmented Metalloimmunotherapy.

The complexity and heterogeneity of individual tumors have hindered the efficacy of existing therapeutic cancer vaccines, sparking intensive interest in the development of more effective in situ vaccines. Herein, we introduce a cancer nanovaccine for reactive oxygen species-augmented metalloimmunotherapy in which FeAl-layered double hydroxide (LDH) is used as a delivery vehicle with dihydroartemisinin (DHA) as cargo. The LDH framework is acid-labile and can be degraded in the tumor microenvironment, releasing iron ions, aluminum ions, and DHA. The iron ions contribute to aggravated intratumoral oxidative stress injury by the synergistic Fenton reaction and DHA activation, causing apoptosis, ferroptosis, and immunogenic cell death in cancer cells. The subsequently released tumor-associated antigens with the aluminum adjuvant form a cancer nanovaccine to generate robust and long-term immune responses against cancer recurrence and metastasis. Moreover, Fe ion-enabled T1-weighted magnetic resonance imaging can facilitate real-time tumor therapy monitoring. This cancer-nanovaccine-mediated metalloimmunotherapy strategy has the potential for revolutionizing the precision immunotherapy landscape.

Predictive nomograms of repeat intrahepatic recurrence and overall survival after radiofrequency ablation of recurrent colorectal liver metastases.

OBJECTIVES: This study was conducted to develop nomograms for predicting repeat intrahepatic recurrence (rIHR) and overall survival (OS), after radiofrequency ablation (RFA), treatment in patients with recurrent colorectal liver metastases (CLMs) after hepatectomy based on clinicopathologic features. METHODS: A total of 160 consecutive patients with recurrent CLMs after hepatectomy who were treated with ultrasound-guided percutaneous RFA from 2012 to 2022 were retrospectively included. Patients were randomly divided into a training cohort and a validation cohort, with a ratio of 8:2. Potential prognostic factors associated with rIHR and OS, after RFA, were identified by using the competing-risks and Cox proportional hazard models, respectively, and were used to construct the nomogram. The nomogram was evaluated by Harrell's C-index and a calibration curve. RESULTS: The 1-, 2-, and 3-year rIHR rates after RFA were 58.8%, 70.2%, and 74.2%, respectively. The 1-, 3- and 5-year OS rates were 96.3%, 60.4%, and 38.5%, respectively. In the multivariate analysis, mutant RAS, interval from hepatectomy to intrahepatic recurrence ≤ 12 months, CEA level >5 ng/ml, and ablation margin <5 mm were the independent predictive factors for rIHR. Mutant RAS, largest CLM at hepatectomy >3 cm, CEA level >5 ng/ml, and extrahepatic disease were independent predictors of poor OS. Two nomograms for rIHR and OS were constructed using the respective significant variables. In both cohorts, the nomogram demonstrated good discrimination and calibration. CONCLUSIONS: The established nomograms can predict individual risk of rIHR and OS after RFA for recurrent CLMs and contribute to improving individualized management.

Interior and Exterior Surface Modification of Zr-Based Metal-Organic Frameworks for Trace Benzene Removal.

The emission of volatile organic compounds (VOCs) significantly contributes to air pollution and poses a serious threat to human health. Benzene, one of the most toxic VOCs, is difficult for the human body to metabolize and is classified as a Group 1 carcinogen. The development of efficient adsorbents for removing trace amounts of benzene from ambient air is thus of great importance. In this work, we studied the benzene adsorption properties of four Zr-based metal-organic frameworks (Zr-MOFs) through static volumetric and dynamic breakthrough experiments. Two previously reported Zr-MOFs, BUT-12 and STA-26, were prepared with a tritopic carboxylic acid ligand (H3L1) functionalized with three methyl groups, and STA-26 is a 2-fold interpenetrated network of BUT-12. Two new isoreticular Zr-MOFs, BUT-12-Et and STA-26-Et, were synthesized using a similar ligand, H3L2, where the methyl groups are replaced with ethyl groups. There are mesopores in BUT-12 and BUT-12-Et and micropores in STA-26 and STA-26-Et. The four Zr-MOFs all showed high stability in liquid water and acidic aqueous solutions. The microporous STA-26 and STA-26-Et showed much higher benzene uptakes than mesoporous BUT-12 and BUT-12-Et at room temperature under low pressures. Particularly, the benzene adsorption capacity of STA-26-Et was high up to 2.21 mmol/g at P/P0 = 0.001 (P0 = 12.78 kPa), higher than those of the other three Zr-MOFs and most reported solid adsorbents. Breakthrough experiments confirmed that STA-26-Et could effectively capture trace benzene (10 ppm) from dry air; however, its benzene capture capacity was reduced by 90% under humid conditions (RH = 50%). Coating of the crystals of STA-26-Et with polydimethylsiloxane (PDMS) increased the hydrophobicity of the exterior MOF surfaces, leading to a more than 2-fold improvement in its benzene capture capacity in the breakthrough experiment under humid condition. PDMS coating of STA-26-Et likely slowed down the water adsorption process, and thus, the adsorbent afforded more efficient capture of benzene. This work demonstrates that modifying both the interior and exterior surfaces of MOFs can effectively enhance their performance in capturing trace benzene from ambient air, even under humid conditions. This finding is meaningful for the development of new adsorbents for effective air purification applications.

T1 Mapping and Amide Proton Transfer Weighted Imaging for Predicting Lymph Node Metastasis in Patients with Rectal Cancer.

BACKGROUND: Accurate preoperative judgment of lymph node (LN) metastasis is a critical step in creating a treatment strategy and evaluating prognosis in rectal cancer (RC) patients. OBJECTIVE: This study aimed to explore the value of T1 mapping and amide proton transfer weighted (APTw) imaging in predicting LN metastasis in patients with rectal cancer. METHODS: In a retrospective study, twenty-three patients with pathologically confirmed rectal adenocarcinoma who underwent MRI and surgery from August 2019 to August 2021 were selected. Then, 3.0T/MR sequences included conventional sequences (T1WI, T2WI, and DWI), APTw imaging, and T1 mapping. Patients were divided into LN metastasis (group A) and non-LN metastasis groups (group B). The intra-group correlation coefficient (ICC) was used to test the inter-observer consistency. Mann-Whitney U test was used to compare the differences between the two groups. Spearman correlation analysis was performed to evaluate the correlation between T1 and APT values. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the differential performance of each parameter and their combination. The difference between AUCs was compared using the DeLong test. RESULTS: The APT value in patients with LN metastasis was significantly higher than in those without LN metastasis group (P=0.020). Also, similar results were observed for the T1 values (P=0.001). The area under the ROC curve of the APT value in the prediction of LN metastasis was 0.794; when the cutoff value was 1.73%, the sensitivity and specificity were 71.4% and 88.9%, respectively. The area under the ROC curve of the T1 value was 0.913; when the cutoff value was 1367.36 ms, the sensitivity and specificity were 78.6% and 100.0%, respectively. The area under the ROC curve of T1+APT was 0.929, with a sensitivity of 78.6% and specificity of 100.0%. CONCLUSION: APT and T1 values show great diagnostic efficiency in predicting LN metastasis in rectal cancer.