Development and preclinical evaluation of a cyclic PET tracer targeting integrin-α6 on colorectal cancer models.

Integrin-α6 is an attractive diagnostic and therapeutic biomarker in cancer, because it is highly expressed in several types of malignancies. Based on our previous findings, we designed a cyclic peptide, NOTA-A6P, to enhancing affinity, tumor uptake and serum stability, and then developed a cyclic radiotracer, [18F]AlF-NOTA-A6P, for the specific detection of early colorectal cancer by PET/CT imaging. [18F] AlF-NOTA-A6P was automatically labeled for colorectal cancer imaging in a novel synthesis module. The affinity, stability, radiochemical yield (RCY), radiochemical purity (RCP), molar activity (Am), and octanol-water partition coefficient of [18F]AlF-NOTA-A6P were investigated. Results demonstrated that the tracer exhibited high serum stability, high RCY (58.1 ± 4.1 %) (undecay-corrected, n = 5) and hydrophilicity. In vivo microPET/CT imaging of LS174T and HT29 xenograft tumor models with high integrin-α6 expression indicated that [18F]AlF-NOTA-A6P exhibited higher tumor uptake and tumor-to-muscle ratio than SW620, which has low integrin-α6 expression. Moreover, the specificity of [18F]AlF-NOTA-A6P for integrin-α6 was confirmed by additional methods, including autoradiography, hematoxylin and eosin staining, and immunohistochemical staining. In conclusion, a cyclic peptide NOTA-A6P targeting integrin-α6 was designed and a promising PET tracer [18F]AlF-NOTA-A6P was synthesized in a novel cassette-type synthesis module. The tracer demonstrated a favorable binding affinity with integrin-α6, stability in human serum and specificity for colorectal cancer xenograft mice. These properties render it a promising non-invasive PET radiotracer for the detection of integrin-α6-overexpressing cancers, including colorectal cancer.

Sandwich Therapy with Radionuclide Combined with Intralesional Injections Based on Differences in the Spatial Structure Components of Keloids.

BACKGROUND: Complications such as ulceration, depigmentation, and recurrence limit the use of intralesional injections and brachytherapy in keloid treatment. We designed a modified "sandwich" therapy based on the spatial distribution of keloid components to reduce the incidence of these complications. METHODS: First, we analyzed the spatial distribution pattern of scar tissue through single-cell sequencing analysis, ultrasound, and pathology. Subsequently, a "sandwich" therapy combining radionuclide and intralesional injections was designed based on the pattern found in the previous stage. Finally, 40 patients with keloid scars at 41 sites were included in the clinical trial. RESULTS: Single-cell sequencing identified two significant cellularly highly expressed genes and enriched pathways in the keloid vascular wall that primarily play essential roles in angiogenesis and promoting collagen synthesis, thereby promoting scar growth. Color ultrasound showed that there were hierarchical differences in the blood supply of the keloid, and further H&E, CD34, and eNOS staining showed that there were hierarchical differences in the spatial structure of blood vessels, fibroblasts, and collagen in the keloid. In clinical studies, the complication rate of "sandwich" therapy is lower than that of conventional treatment. CONCLUSION: The distribution of blood vessels and collagen in keloid scars is characterized by spatial variability. The "sandwich" therapy of radionuclide combined with intralesional injections is a modified type of precisely targeted therapy designed based on this variability; it has fewer complications and good clinical efficacy and is worthy of popularization. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Role of sRNAs protein molecules in extracellular vesicles derived from Lactobacillus plantarum rejuvenate against ultraviolet B-induced photoaging in human keratinocytes.

Ultraviolet B (UVB) radiation accelerates the aging process of skin cells by triggering oxidative stress and inflammatory responses. The aim of this study was to investigate the mechanism of action of sRNAs and protein molecules in the regenerative extracellular vesicles of Lactobacillus plantarum against the UVB-induced photoaging process of human keratinocytes. The extracellular vesicles regenerated by Lactobacillus plantarum were isolated and purified to identify sRNAs and protein components. Human keratinocytes were treated with UVB radiation to simulate the photoaging model. The effects of different concentrations of vesicle extract on cell survival rate, oxidative stress index and inflammatory marker expression were evaluated in control group and treatment group. The results showed that the regenerated extracellular vesicles of L. plantarum significantly improved the survival rate of keratinocytes after UVB radiation, and delayed the aging process of skin cells by reducing oxidative stress and inhibiting inflammatory response.

Modulation transfer function of implantable phakic intraocular contact lens (IPCL) for myopia and presbyopia.

PURPOSE: This study aimed to assess the optical quality of myopic and presbyopic IPCLs with different additional powers, and to investigate the effects of pupil size on the optical quality of these IPCLs using an in-vitro modulation transfer function (MTF) measurement system. METHODS: Linear scatter functions (LSFs) were recorded using the OPAL Vector system and an eye phantom consisting of wet cells filled with a balanced salt solution. A myopic IPCL or a presbyopic IPCL was placed in the posterior chamber of this model. The MTF was calculated from the LSF using the fast Fourier transform techniques. The effective apertures were set at 2.0 to 5.0 mm in 1.0 mm steps. RESULTS: The in-focus MTF values of the myopic IPCL and presbyopic IPCL with additional powers of + 2.0 and + 4.0 diopters at 100 cycles/mm for an effective aperture of 3.0 mm were 43%, 27%, and 24%, respectively. The in-focus MTF value of both myopic and presbyopic IPCLs was the highest when the effective aperture was set at 3.0 mm, and it gradually worsened when the effective aperture became larger than 3.0 mm at 20, 60, and 100 cycles/mm. CONCLUSIONS: Both myopic and presbyopic IPCLs provided excellent MTF values, but the additional power profile can deteriorate optical performance in presbyopic IPCL-implanted eyes, even with a low additional power. Pupil size can influence visual quality in IPCL-implanted eyes for both myopia and presbyopia.

A pan-KRAS degrader for the treatment of KRAS-mutant cancers.

KRAS mutations are highly prevalent in a wide range of lethal cancers, and these mutant forms of KRAS play a crucial role in driving cancer progression and conferring resistance to treatment. While there have been advancements in the development of small molecules to target specific KRAS mutants, the presence of undruggable mutants and the emergence of secondary mutations continue to pose challenges in the clinical treatment of KRAS-mutant cancers. In this study, we developed a novel molecular tool called tumor-targeting KRAS degrader (TKD) that effectively targets a wide range of KRAS mutants. TKD is composed of a KRAS-binding nanobody, a cell-penetrating peptide selectively targeting cancer cells, and a lysosome-binding motif. Our data revealed that TKD selectively binds to KRAS in cancer cells and effectively induces KRAS degradation via a lysosome-dependent process. Functionally, TKD suppresses tumor growth with no obvious side effects and enhances the antitumor effects of PD-1 antibody and cetuximab. This study not only provides a strategy for developing drugs targeting "undruggable" proteins but also reveals that TKD is a promising therapeutic for treating KRAS-mutant cancers.

Research progress on asialoglycoprotein receptor-targeted radiotracers designed for hepatic nuclear medicine imaging.

Asialoglycoprotein receptor (ASGPR) specifically recognizes glycans terminated with ß-d-galactose or N-acetylgalactosamine. Its exclusive expression in mammalian hepatocytes renders it an ideal hepatic-targeted biomarker. To date, ASGPR-targeted ligands have been actively developed for drug delivery and hepatic imaging. This review provides a comprehensive summary of the progress achieved to-date in the field of developing ASGPR-targeted nuclear medicine imaging (NMI) radiotracers, highlighting the recent advancements over the last decade in terms of structure, radionuclides and labeling strategies. The biodistribution patterns, imaging characteristics, challenges and future prospective are discussed.

Imaging diagnosis and efficacy monitoring by [89Zr]Zr-DFO-KN035 immunoPET in patients with PD-L1-positive solid malignancies.

Rationale: Although programmed death-ligand 1 (PD-L1) inhibitors have achieved efficacy in cancer therapy, their response rate is low. Differences in the prognosis of patients with cancer under anti-PD-L1 treatment are related to the PD-L1 level in tumors. Accurate PD-L1 detection can optimize the accuracy of tumor immunotherapy and avoid ineffective clinical diagnosis and treatments. Methods: We investigated the imaging efficiency and therapy monitoring capacity of [89Zr]Zr-DFO-KN035 immunoPET for tumors. We labeled the monodomain anti-PD-L1 antibody KN035 with the radionuclide zirconium-89 and used this tracer for PET imaging. [89Zr]Zr-DFO-KN035 uptakes in patients with PD-L1-positive tumors, including primary and metastatic tumors, as well as in normal tissues, were comparatively assessed by using positron emission tomography/computed tomography imaging. Results: In PD-L1-positive patients, [89Zr]Zr-DFO-KN035 was sensitive in tumor-targeting imaging and could detect multiple metastatic foci, including multiple bone metastases (tumor-to-muscle ratios of 7.102 and 6.118 at 55 and 120 h, respectively) and lymph-node metastases (tumor-to-muscle ratios of 11.346 and 6.542 at 55 and 120 h, respectively). The needed radioactive dose of [89Zr]Zr-DFO-KN035 (55.5-92.5 MBq) used in this study was considerably lower than that of [18F]FDG (370-555 MBq). [89Zr]Zr-DFO-KN035 monitored and predicted the site of adverse reactions in antitumor immunotherapy. Moreover, after antitumor treatment, [89Zr]Zr-DFO-KN035 enabled observational imaging for therapeutic efficacy evaluation, which can help predict patient prognosis. Conclusion: [89Zr]Zr-DFO-KN035 can be used for the diagnosis and therapy monitoring of PD-L1-positive tumors and provide noninvasive and comprehensive observations for tumor diagnostic imaging, prognosis prediction, and efficacy evaluation.

A novel PSMA targeted dual-function near-infrared fluorescence and PET probe for the image-guided surgery and detection of prostate cancer.

PURPOSE: Prostate-specific membrane antigen (PSMA) is a promising diagnostic biomarker for prostate cancer (PCa). NYM016, a novel small-molecule PSMA-targeted fluorescence probe for the surgical navigation of PCa, was designed in this work. Furthermore, the potential of the PET agent [68Ga]Ga-NYM016 for the radionuclide imaging of PCa was evaluated. METHODS: NYM016 was designed with the near-infrared fluorescent group Cyanine 7 (Cy7) and the chelating group NOTA. The radioactive probe [68Ga]Ga-NYM016 was designed and synthesized on the basis of NYM016. The abovementioned probes were assessed in PSMA-positive xenograft-bearing models and patients diagnosed with PCa. RESULTS: NYM016 obviously aggregated in the tumor site of the mouse model, and its fluorescence intensity was stable within 24 h. NYM016 was well-tolerated, and no adverse events were found in the clinical study. Moreover, it was also observed in the excised lesions from the patient with PCa, and its fluorescence aggregated at the same site where PSMA was highly expressed. In addition, the PSMA xenograft demonstrated intense [68Ga]Ga-NYM016 uptake at 2.5 min after injection. At 3 h after injection, [68Ga]Ga-NYM016 uptake by the PSMA xenograft gradually increased to 6.40 ± 0.19%ID/g, which was higher that by the blocked and negative groups (2.28 ± 0.07%ID/g, P < 0.05; 2.28 ± 0.22%ID/g, P < 0.05). In the clinical study, [68Ga]Ga-NYM016 was well-tolerated and no adverse events were observed. Substantial accumulation was observed in primary and metastatic lesions in a patient with recurrence with the maximum standardized uptake value of 18.93. Meanwhile, negative [68Ga]Ga-NYM016 uptake was observed at the prostate site of a patient with prostatitis. CONCLUSION: The novel fluorescence probe NYM016 and the radioactive tracer [68Ga]Ga-NYM016 are promising candidates for the surgical navigation and radionuclide imaging of PCa, respectively. TRIAL REGISTRATION: The clinical evaluation of this study was registered at Clinicaltrial.gov (NCT05623878) on 21 Dec, 2022.

Identify the potential driving mechanism of reconstructed bacterial community in reduce CO2 emissions and promote humus formation during cow manure composting.

The mineralization of organic components releases CO2 during composting, which not only leads to the loss of organic carbon, but has a direct negative impact on the environment. Malonic acid as a competitive inhibitor of succinate dehydrogenase could affect the tricarboxylic acid (TCA) cycle and reduce CO2 emissions. However, the bacterial interaction and organic component transformation has less known how to malonic acid reduce CO2 and improve of humus synthesis in complex composting. The aim of this study was to investigated the malonic acid on organic carbon sequestration and transforming cow manure waste into products with high humus content. Humus content was elevated by 16.8% and cumulative CO2 emissions (30 d)d reduced by 13.6% after malonic acid addition compared to the CK. SparCC analysis of bacterial interaction presented that the network complexity and stability was more higher with malonic acid addition, while a greater concentration of keystones and their ecological metabolic functions was observed, suggesting they weaken the influence of TCA cycle inhibition by enhancing interactions. PICRUSt predictions indicate that malonic acid might enhance humus content by promoting the synthesis of polyphenols and polymerization with amino acids. This study investigated the potential mechanism of regulators to enhance quality and reduce emissions during humification process, providing a new strategy for the resource utilization of organic solid waste.

Radiomic signatures based on pretreatment 18F-FDG PET/CT, combined with clinicopathological characteristics, as early prognostic biomarkers among patients with invasive breast cancer.

Purpose: The aim of this study was to investigate the predictive role of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in the prognostic risk stratification of patients with invasive breast cancer (IBC). To achieve this, we developed a clinicopathologic-radiomic-based model (C-R model) and established a nomogram that could be utilized in clinical practice. Methods: We retrospectively enrolled a total of 91 patients who underwent preoperative 18F-FDG PET/CT and randomly divided them into training (n=63) and testing cohorts (n=28). Radiomic signatures (RSs) were identified using the least absolute shrinkage and selection operator (LASSO) regression algorithm and used to compute the radiomic score (Rad-score). Patients were assigned to high- and low-risk groups based on the optimal cut-off value of the receiver operating characteristic (ROC) curve analysis for both Rad-score and clinicopathological risk factors. Univariate and multivariate Cox regression analyses were performed to determine the association between these variables and progression-free survival (PFS) or overall survival (OS). We then plotted a nomogram integrating all these factors to validate the predictive performance of survival status. Results: The Rad-score, age, clinical M stage, and minimum standardized uptake value (SUVmin) were identified as independent prognostic factors for predicting PFS, while only Rad-score, age, and clinical M stage were found to be prognostic factors for OS in the training cohort. In the testing cohort, the C-R model showed superior performance compared to single clinical or radiomic models. The concordance index (C-index) values for the C-R model, clinical model, and radiomic model were 0.816, 0.772, and 0.647 for predicting PFS, and 0.882, 0.824, and 0.754 for OS, respectively. Furthermore, decision curve analysis (DCA) and calibration curves demonstrated that the C-R model had a good ability for both clinical net benefit and application. Conclusion: The combination of clinicopathological risks and baseline PET/CT-derived Rad-score could be used to evaluate the prognosis in patients with IBC. The predictive nomogram based on the C-R model further enhanced individualized estimation and allowed for more accurate prediction of patient outcomes.

Exploration of potential driving mechanisms of Comamonas testosteroni in polycyclic aromatic hydrocarbons degradation and remodelled bacterial community during co-composting.

Polycyclic aromatic hydrocarbons (PAHs) are a cluster of highly hazardous organic pollutants that are widespread in ecosystems and threaten human health. Composting has been shown to be an effective strategy for PAHs degredation. Here, we used Comamonas testosteroni as an inoculant in composting and investigated the potential mechanisms of PAHs degradation by co-occurrence network and structural equation modelling analysis. The results showed that more than 60% of PAHs were removed and the bacterial community responded to the negative effects of PAHs by upgrading the network. Inoculation with C. testosteroni altered bacterial community succession, intensified bacterial response to PAHs, improved metabolic activity, and promoted the degradation of PAHs during co-composting. The increased in the positive cohesion index of the community suggested that agents increased the cooperative behaviour between bacteria and led to changes in keystones of the bacterial network. However, the topological values of C. testosteroni in the network were not elevated, which confirmed that C. testosteroni altered communities by affecting other bacterial growth rather than its own colonisation. This study strengthens our comprehension of the potential mechanisms for the degradation of PAHs in inoculated composting.

Assessment of androgen receptor expression in breast cancer patients using 18 F-FDG PET/CT radiomics and clinicopathological characteristics.

OBJECTIVE: In the present study, we mainly aimed to predict the expression of androgen receptor (AR) in breast cancer (BC) patients by combing radiomic features and clinicopathological factors in a non-invasive machine learning way. MATERIALS AND METHODS: A total of 48 BC patients, who were initially diagnosed by 18F-FDG PET/CT, were retrospectively enrolled in this study. LIFEx software was used to extract radiomic features based on PET and CT data. The most useful predictive features were selected by the LASSO (least absolute shrinkage and selection operator) regression and t-test. Radiomic signatures and clinicopathologic characteristics were incorporated to develop a prediction model using multivariable logistic regression analysis. The receiver operating characteristic (ROC) curve, Hosmer-Lemeshow (H-L) test, and decision curve analysis (DCA) were conducted to assess the predictive efficiency of the model. RESULTS: In the univariate analysis, the metabolic tumor volume (MTV) was significantly correlated with the expression of AR in BC patients (p < 0.05). However, there only existed feeble correlations between estrogen receptor (ER), progesterone receptor (PR), and AR status (p = 0.127, p = 0.061, respectively). Based on the binary logistic regression method, MTV, SHAPE_SphericityCT (CT Sphericity from SHAPE), and GLCM_ContrastCT (CT Contrast from grey-level co-occurrence matrix) were included in the prediction model for AR expression. Among them, GLCM_ContrastCT was an independent predictor of AR status (OR = 9.00, p = 0.018). The area under the curve (AUC) of ROC in this model was 0.832. The p-value of the H-L test was beyond 0.05. CONCLUSIONS: A prediction model combining radiomic features and clinicopathological characteristics could be a promising approach to predict the expression of AR and noninvasively screen the BC patients who could benefit from anti-AR regimens.

Automated Synthesis and Preclinical Evaluation of Optimized Integrin α6-Targeted Positron Emission Tomography Imaging of Pancreatic Cancer.

Integrin α6 has been considered a promising biomarker, is overexpressed in many tumors, and plays a vital role in tumor formation, recurrence, and metastasis. In this study, we identified a novel high-affinity integrin α6-targeted peptide named RD2 (Arg-Trp-Tyr-Asp-PEG4)2-Lys-Lys and developed a 18F-radiolabeled peptide tracer ([18F]-AlF-NOTA-RD2) and evaluated its potential application in positron emission tomography (PET) imaging of pancreatic cancer. [18F]-AlF-NOTA-RD2 was produced using GMP (Good Manufacturing Practice of Medical Products)-compliant automatic radiosynthesis on a single GE FASTLab2 cassette-type synthesis module. The stability of [18F]-AlF-NOTA-RD2 was analyzed in phosphate-buffered saline (PBS) and fetal bovine serum (FBS). The cell uptake assay of the tracer was assessed using PANC-1 cells. In addition, small-animal PET imaging and biodistribution studies of [18F]-AlF-NOTA-RD2 were performed in pancreatic cancer subcutaneous tumor-bearing mice. The PET tracer [18F]-AlF-NOTA-RD2 was obtained with a radiochemical yield of 23.7 ± 4.7%, radiochemical purity of >99%, and molar activity of 165.7 ± 59.1 GBq/µmol. [18F]-AlF-NOTA-RD2 exhibited good in vitro stability in PBS and FBS. LogP octanol water value for the tracer was -2.28 ± 0.05 (n = 3). The binding affinity of RD2 to the integrin α6 protein (Kd = 0.13 ± 3.65 µM, n = 3) was significantly higher than that of the RWY (CRWYDENAC) (Kd = 6.97 ± 1.44 µM, n = 3). Small-animal PET imaging and biodistribution also revealed that [18F]-AlF-NOTA-RD2 displayed rapid and good tumor uptake and lower liver background uptake in PANC-1 tumor-bearing mice. [18F]-AlF-NOTA-RD2 showed significant radioactivity accumulation in tumors and was successfully blocked by NOTA-RD2. Compared with [18F]-FDG, [18F]-AlF-NOTA-RD2 PET imaging and biodistribution studies in PANC-1 xenograft tumor-bearing mice confirmed a good tumor-to-muscle ratio (8.69 ± 2.03 vs 1.41 ± 0.23, respectively) at 0.5 h and (2.99 ± 3.02 vs 1.43 ± 0.17, respectively) at 1 h post injection. Autoradiography of human pancreatic cancer tumor tissues further confirmed high accumulation of [18F]-AlF-NOTA-RD2. In summary, we developed an optimized integrin α6-targeted imaging tracer and obtained high radioactivity products with a cassette-type synthesis module; moreover, the tracer exhibited good binding affinity with integrin α6 and good target specificity for PANC-1 cells in xenograft pancreatic tumor-bearing mice, demonstrating its promising application as a noninvasive PET radiotracer of integrin α6 expression in pancreatic cancer.

Brain glucose metabolism on [18F]-FDG PET/CT: a dynamic biomarker predicting depression and anxiety in cancer patients.

Objectives: To explore the correlation between the incidence rates of depression and anxiety and cerebral glucose metabolism in cancer patients. Methods: The experiment subjects consisted of patients with lung cancer, head and neck tumor, stomach cancer, intestinal cancer, breast cancer and healthy individuals. A total of 240 tumor patients and 39 healthy individuals were included. All subjects were evaluated by the Hamilton depression scale (HAMD) and Manifest anxiety scale (MAS), and were examined by whole body Positron Emission Tomography/Computed Tomography (PET/CT) with 18F-fluorodeoxyglucose (FDG). Demographic, baseline clinical characteristics, brain glucose metabolic changes, emotional disorder scores and their relations were statistically analyzed. Results: The incidence rates of depression and anxiety in patients with lung cancer were higher than those in patients with other tumors, and Standard uptake values (SUVs) and metabolic volume in bilateral frontal lobe, bilateral temporal lobe, bilateral caudate nucleus, bilateral hippocampus, left cingulate gyrus were lower than those in patients with other tumors. We also found that poor pathological differentiation, and advanced TNM stage independently associated with depression and anxiety risk. SUVs in the bilateral frontal lobe, bilateral temporal lobe, bilateral caudate nucleus, bilateral hippocampus, left cingulate gyrus were negatively correlated with HAMD and MAS scores. Conclusion: This study revealed the correlation between brain glucose metabolism and emotional disorders in cancer patients. The changes in brain glucose metabolism were expected to play a major role in emotional disorders in cancer patients as psychobiological markers. These findings indicated that functional imaging can be applied for psychological assessment of cancer patients as an innovative method.

Exosomal B7-H3 facilitates colorectal cancer angiogenesis and metastasis through AKT1/mTOR/VEGFA pathway.

B7-H3 (CD276), an immune checkpoint molecule, is aberrantly overexpressed in many types of cancer, and plays important roles in tumor immune evasion, carcinogenesis and metastasis, as well as angiogenesis. However, the mechanisms underlying B7-H3-promoted angiogenesis are still largely unknown. In this study, based on the observation of overexpression of B7-H3 on the tumor cells and vascular endothelial cells (VECs) in colorectal cancer (CRC) tissues, we investigated the roles of cancer cell-drived exosomal B7-H3 in tumor angiogenesis and metastasis through crosstalk between cancer cells and VECs. We found that CRC cell-drived exosomal B7-H3 was uptaken by human umbilical vein endothelial cells (HUVECs) and consequently activated the AKT serine/threonine kinase 1 (AKT1) / mechanistic target of rapamycin kinase (mTOR) / vascular endothelial growth factor A (VEGFA) signaling pathway, thus augmenting the abilities of migration, invasion and tube formation of HUVECs. Furthermore, administration of CRC cell-drived exosomes with reinforced B7-H3 promoted the pulmonary angiogenesis and metastasis of CRC cells in mice. In addition, high expression of B7-H3 was observed in urinary exosomes isolated from CRC patients. Our findings reveal that CRC-derived exosomal B7-H3 promotes tumor angiogenesis and metastasis by activating the AKT1/mTOR/VEGFA signaling pathway. It provides novel insights into the roles of CRC-drived exosomes in CRC progression.

Bibliometric analysis of ferroptosis: a comprehensive evaluation of its contribution to cancer immunity and immunotherapy.

Background: In the past 5 years, ferroptosis-associated cancer immunity has been attracted significant research interest. Objective: This study was performed to identify and analyze the global output trend for ferroptosis in cancer immunity. Methods: Relevant studies were retrieved from the Web of Science Core Collection on Feb 10th, 2023. The VOSviewer and Histcite softwares were utilized to perform the visual bibliometric and deep mining analyses. Results: A total of 694 studies (530 articles (76.4%) and 164 (23.6%) review articles) were retrieved from the Web of Science Core Collection for visualization analyses. The top 3 key keywords were ferroptosis, prognosis and immunotherapy. The top 30 local citation score (LCS) authors were all collaborators of Zou Weiping. Deep mining of 51 nanoparticle-related articles showed that BIOMATERIALS was the most popular journal. The primary goal of gene signatures related to ferroptosis and cancer immunity was to establish prognostic predictions. Conclusion: There has been a significant increase in ferroptosis-associated immune publications in the recent 3 years. The key research hotspots include mechanisms, prediction and therapeutic outcomes. The most influential article was from the Zou Weiping's group, which proposed that system xc-mediated ferroptosis is induced by CD8(+) T cell-secreted IFNγ after PD-L1 blockage for immunotherapy. The frontier of research in the field of ferroptosis-associated immune is the study on nanoparticle and gene signature The limitation of this bibliometric study is that publications on this topic are few.

Metabolite-assisted models improve risk prediction of coronary heart disease in patients with diabetes.

Background: Patients with diabetes have a two-to four-fold increased incidence of cardiovascular diseases compared with non-diabetics. Currently, there is no recognized model to predict the occurrence and progression of CVDs in diabetics. Objective: This work aimed to develop a metabolic biomarker-assisted model, a combination of metabolic markers with clinical variables, for risk prediction of CVDs in diabetics. Methods: A total of 475 patients with diabetes were studied. Each patient underwent coronary angiography. Plasma samples were analyzed by liquid chromatography-quadrupole time-of-flight mass spectrometry. Ordinal logistic regression and random forest were used to screen metabolites. Receiver operating characteristic (ROC) curve, nomogram, and decision curve analysis (DCA) were employed to evaluate their prediction performances. Results: Ordinal logistic regression screened out 34 differential metabolites (adjusted-false discovery rate p < 0.05) from 2059 ion features by comparisons of diabetics with and without CVDs. Random forest identified methylglutarylcarnitine and lysoPC (18:0) as the metabolic markers (mean decrease gini >1.0) for non-significant CVDs (nos-CVDs) versus normal coronary artery (NCA), 1,3-Octadiene and 3-Octanone for acute coronary syndrome (ACS) versus nos-CVDs, and lysoPC (18:0) for acute coronary syndrome versus normal coronary artery. For risk prediction, the metabolic marker-assisted models provided areas under the curve of 0.962-0.979 by ROC (0.576-0.779 for the base models), and c-indices of 0.8477-0.9537 by nomogram analysis (0.1514-0.5196 for the base models). Decision curve analysis (DCA) showed that the models produced greater benefits throughout a wide range of risk probabilities compared with the base model. Conclusion: Metabolic biomarker-assisted model remarkably improved risk prediction of cardiovascular disease in diabetics (>90%).

Development of a multifunctional platform for near-infrared imaging and targeted radionuclide therapy for tumors.

Biotin receptor (BR) is overexpressed in several human tumor cell lines and has become an important biomarker for tumor diagnosis and treatment. Therefore, much attention has been attracted in the field of developing BR-targeting agents. In clinical practice, a multifunctional platform that can be used for both diagnosis and treatment is much desirable. In this study, to improve diagnostic and therapeutic efficacy of BR-positive tumors, we developed a multifunctional platform RT-H2 to combine with the cyanine scaffold for near infrared (NIR) imaging and the radioisotope 131I for targeted radionuclide therapy (TRT). In vitro experiments showed that RT-H2 possessed favorable NIR properties and could selectively accumulate in BR-positive HeLa cells. In vivo NIR imaging of HeLa tumor-bearing mice exhibited high accumulation and long retention time (72 h) of RT-H2 in the tumor. Furthermore, RT-H2 was also employed as a carrier to develop 131I-labeled TRT agent due to its favorable properties in vivo. The radiolabeling conditions were optimized and the optimal conditions determined to be 1.2 equiv of Idogen, reaction time 4 min and room temperature, yielding the radiotracer [131I]I-RT-H2 with the radiochemical purity (RCP) of > 95% after a simple purification by a C18 column. In vitro cell experiments indicated that [131I]I-RT-H2 could specifically target Hela cells and displayed dose-dependent antitumor effect. In vivo experiments demonstrated that [131I]I-RT-H2 obviously inhibited the tumor proliferation in HeLa tumor-bearing mice within 4 weeks. All these results indicate that RT-H2 has the potential to serve as a multifunctional platform for tumor diagnosis and treatment.

EDB-FN targeted probes for the surgical navigation, radionuclide imaging, and therapy of thyroid cancer.

PURPOSE: Extradomain B of fibronectin (EDB-FN) is a promising diagnostic and therapeutic biomarker for thyroid cancer (TC). Here, we identified a high-affinity EDB-FN targeted peptide named EDBp (AVRTSAD) and developed three EDBp-based probes, Cy5-PEG4-EDBp(Cy5-EDBp), [18F]-NOTA-PEG4-EDBp([18F]-EDBp), and [177Lu]-DOTA-PEG4-EDBp ([177Lu]-EDBp), for the surgical navigation, radionuclide imaging, and therapy of TC. METHODS: Based on the previously identified EDB-FN targeted peptide ZD2, the optimized EDB-FN targeted peptide EDBp was identified by using the alanine scan strategy. Three EDBp-based probes, Cy5-EDBp, [18F]-EDBp, and [177Lu]-EDBp, were developed for fluorescence imaging, positron emission tomography (PET) imaging, and radiotherapy in TC tumor-bearing mice, respectively. Additionally, [18F]-EDBp was evaluated in two TC patients. RESULTS: The binding affinity of EDBp to the EDB fragment protein (Kd = 14.4 ± 1.4 nM, n = 3) was approximately 336-fold greater than that of the ZD2 (Kd = 4839.7 ± 361.7 nM, n = 3). Fluorescence imaging with Cy5-EDBp facilitated the complete removal of TC tumors. [18F]-EDBp PET imaging clearly delineated TC tumors, with high tumor uptake (16.43 ± 1.008%ID/g, n = 6, at 1-h postinjection). Radiotherapy with [177Lu]-EDBp inhibited tumor growth and prolonged survival in TC tumor-bearing mice (survival time of different treatment groups: saline vs. EDBp vs. ABRAXANE vs. [177Lu]-EDBp = 8.00 d vs. 8.00 d vs. 11.67 d vs. 22.33 d, ***p < 0.001). Importantly, the first-in-human evaluation of [18F]-EDBp demonstrated that it had specific targeting properties (SUVmax value of 3.6) and safety. CONCLUSION: Cy5-EDBp, [18F]-EDBp, and [177Lu]-EDBp are promising candidates for the surgical navigation, radionuclide imaging, and radionuclide therapy of TC, respectively.

Exploration of bacterial community-induced polycyclic aromatic hydrocarbons degradation and humus formation during co-composting of cow manure waste combined with contaminated soil.

To solve polycyclic aromatic hydrocarbons (PAHs) pollution, composting was chosen as a remediation method. During composting, the dissipation of PAHs was carried out by resource utilization of organic solid waste and its degradation by bacteria. This study was conducted by co-composting with contaminated soil and cow manure. The results showed that the degradation rates of naphthalene (Nap), phenanthrene (Phe), and benzo[α]pyrene (BaP) could reach 82.2%, 79.4%, and 59.6% respectively during composting. Cluster analysis indicated that polyphenol oxidase (PPO), laccase, and protease were important drivers of PAHs transformation. The content of humic substances (HS) was 106.67 g/kg in PAH treatment, which was significantly higher than that in the control group at 65 days. The phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) and network analysis was used to infer the degradation mechanism of PAHs by microorganisms. The degradation of PAHs by PPO was found to have a significant contribution to the formation of HS. It was shown that PAHs and metabolic intermediates were more inclined to be oxidized and decomposed by PPO to form quinone, which in turn condensed with amino acids to form HS. Composting could promote the degradation of PAHs while improving the quality of compost, achieving a win-win situation.