Deep Electron Redistributions Induced by Dual Junctions Facilitating Electroreduction of Dilute Nitrate to Ammonia.

The electronic states of metal catalysts can be redistributed by the rectifying contact between metal and semiconductor e.g., N-doped carbon (NC), while the interfacial regulation degree is very limited. Herein, a deep electronic state regulation is achieved by constructing a novel double-heterojunctional Co/Co3O4@NC catalyst containing Co/Co3O4 and Co3O4/NC heterojunctions. When used for dilute electrochemical NO3 - reduction reaction (NO3RR), the as-prepared Co/Co3O4@NC exhibits an outstanding Faradaic efficiency for NH3 formation (FENH3) of 97.9%, -0.4 V versus RHE and significant NH3 yield of 303.5 mmol h-1 gcat -1 at -0.6 V at extremely low nitrate concentrations (100 ppm NO3 --N). Experimental and theoretical results reveal that the dual junctions of Co/Co3O4 and Co3O4/NC drive a unidirectional electron transfer from Co to NC (Co→Co3O4→NC), resulting in electron-deficient Co atoms. The electron-deficient Co promotes NO3 - adsorption, the rate-determining step (RDS) for NO3RR, facilitating the dilute NO3RR to NH3. The design strategy provides a novel reference for unidirectional multistage regulation of metal electronic states boosting electrochemical dilute NO3RR, which opens up an avenue for deep electronic state regulation of electrocatalyst breaking the limitation of the electronic regulation degree by rectifying contact.

Can We Differentiate Between Primary Sjögren Syndrome and Idiopathic Multicentric Castleman Disease Based on the Characteristics of Pulmonary Cysts?

PURPOSE: To identify radiological characteristics that could help differentiate cystic lung diseases between primary Sjögren syndrome (pSS) and idiopathic multicentric Castleman disease (iMCD). PATIENTS AND METHODS: Patients with pSS or iMCD who had cysts were enrolled. Cyst characteristics (number, size, morphology, and distribution) and other accompanying manifestations (nodules, ground-glass opacities, calcification, and thickening of the bronchovascular bundles and interlobular septa) were compared between them. RESULTS: Eleven patients with pSS and 25 patients with iMCD were eligible for our study. Eleven patients with pSS (100.0%) and 23 patients with iMCD (92.0%) had round or oval cysts. None of the patients with pSS had irregular cysts, but 21 (84.0%) patients with iMCD had irregular cysts (P = 0.005). Smooth-walled cysts were present in 11 patients with pSS (100.0%) and 18 patients with iMCD (72.0%). Only 1 patient with pSS (9.1%) exhibited non-smooth-walled cysts, whereas 23 patients with iMCD (92.0%) had non-smooth-walled cysts (P = 0.003). The presence of nodules was common in both groups (P = 1.000). However, the nodules were more likely to be larger and more numerous in patients with iMCD (P < 0.001). Cysts with mural nodules (52.2%) and central nodules (47.8%) were only observed in iMCD (P = 0.007). CONCLUSION: Although regular and smooth-walled cysts were common in the 2 diseases, irregular and non-smooth-walled cysts were more often associated with iMCD than pSS. Nodules in iMCD tended to be larger and more numerous, and a close positional relationship between nodules and cysts was only observed in iMCD.

Nerolidol rescues hippocampal injury of diabetic rats through inhibiting NLRP3 inflammasome and regulation of MAPK/AKT pathway.

Despite the observation of diabetes-induced brain tissue damage and impaired learning and memory, the underlying mechanism of damage remains elusive, and effective, targeted therapeutics are lacking. Notably, the NLRP3 inflammasome is highly expressed in the hippocampus of diabetic individuals. Nerolidol, a naturally occurring compound with anti-inflammatory and antioxidant properties, has been identified as a potential therapeutic option for metabolic disorders. However, the ameliorative capacity of nerolidol on diabetic hippocampal injury and its underlying mechanism remain unclear. Network pharmacology and molecular docking was used to predict the signaling pathways and therapeutic targets of nerolidol for the treatment of diabetes. Then established a diabetic rat model using streptozotocin (STZ) combined with a high-fat diet and nerolidol was administered. Morris water maze to assess spatial learning memory capacity. Hematoxylin and eosin and Nissl staining was used to detect neuronal damage in the diabetic hippocampus. Transmission electron microscopy was used to detect the extent of damage to mitochondria, endoplasmic reticulum (ER) and synapses. Immunofluorescence was used to detect GFAP, IBA1, and NLRP3 expression in the hippocampus. Western blot was used to detect apoptosis (Bcl-2, BAX, and Cleaved-Caspase-3); synapses (postsynaptic densifying protein 95, SYN1, and Synaptophysin); mitochondria (DRP1, OPA1, MFN1, and MFN2); ER (GRP78, ATF6, CHOP, and caspase-12); NLRP3 inflammasome (NLRP3, ASC, and caspase-1); inflammatory cytokines (IL-18, IL-1ß, and TNF-α); AKT (P-AKT); and mitogen-activated protein kinase (MAPK) pathway (P-ERK, P-p38, and P-JNK) related protein expression. Network pharmacology showed that nerolidol's possible mechanisms for treating diabetes are the MAPK/AKT pathway and anti-inflammatory effects. Animal experiments demonstrated that nerolidol could improve blood glucose, blood lipids, and hippocampal neuronal damage in diabetic rats. Furthermore, nerolidol could improve synaptic, mitochondrial, and ER damage in the hippocampal ultrastructure of diabetic rats by potentially affecting synaptic, mitochondrial, and ER-related proteins. Further studies revealed that nerolidol decreased neuroinflammation, NLRP3 and inflammatory factor expression in hippocampal tissue while also decreasing MAPK pathway expression and enhancing AKT pathway expression. However, nerolidol improves hippocampal damage in diabetic rats cannot be shown to improve cognitive function. In conclusion, our study reveals for the first time that nerolidol can ameliorate hippocampal damage, neuroinflammation, synaptic, ER, and mitochondrial damage in diabetic rats. Furthermore, we suggest that nerolidol may inhibit NLRP3 inflammasome and affected the expression of MAPK and AKT. These findings provide a new experimental basis for the use of nerolidol to ameliorate diabetes-induced brain tissue damage and the associated disease.

Plasmodium yoelii surface-related antigen (PySRA) modulates the host pro-inflammatory responses via binding to CD68 on macrophage membrane.

Malaria, one of the major infectious diseases in the world, is caused by the Plasmodium parasite. Plasmodium antigens could modulate the inflammatory response by binding to macrophage membrane receptors. As an export protein on the infected erythrocyte membrane, Plasmodium surface-related antigen (SRA) participates in the erythrocyte invasion and regulates the immune response of the host. This study found that the F2 segment of P. yoelii SRA activated downstream MAPK and NF-κB signaling pathways by binding to CD68 on the surface of the macrophage membrane and regulating the inflammatory response. The anti-PySRA-F2 antibody can protect mice against P. yoelii, and the pro-inflammatory responses such as IL-1ß, TNF-α, and IL-6 after infection with P. yoelii are attenuated. These findings will be helpful for understanding the involvement of the pathogenic mechanism of malaria with the exported protein SRA.

HOXB9 promotes osteosarcoma cell survival and malignancy under glucose starvation via upregulating SPP1 expression.

Homeobox B9 (HOXB9) has been shown to play a critical role in several tumors. However, the precise biological mechanisms and functions of HOXB9 in osteosarcoma remain largely unknown. In this study, we found that HOXB9 was increased upon glucose starvation. Elevated HOXB9 suppressed osteosarcoma cell death and supported cell growth and migration under glucose starvation. Further mechanistic studies demonstrated that HOXB9 directly bound to the promoter of secreted phosphoprotein 1 (SPP1) and transcriptionally upregulated SPP1 expression which then led cell death decrease and cell growth increase under glucose deprivation environment. Clinically, HOXB9 was significantly upregulated in osteosarcoma compared with normal tissues and increase of HOXB9 expression was positively associated with the elevation of SPP1 in osteosarcoma. Overall, our study illustrates that HOXB9 contributes to malignancy in osteosarcoma and inhibits cell death through transcriptional upregulating SPP1 under glucose starvation.

Disulfidptosis-related lncRNA signature reveals immune microenvironment and novel molecular subtyping of stomach adenocarcinoma.

The main challenge in treating stomach adenocarcinoma (STAD) is chemotherapy resistance, which is characterized by changes in the immune microenvironment. Disulfidptosis, a novel form of programmed cell death, is involved in STAD but its mechanism is not fully understood. Long non-coding RNAs (LncRNAs) may play a role in regulating disulfidptosis and influencing the immune microenvironment and chemotherapy resistance in STAD. This study aims to establish disulfidptosis-related lncRNA (DRL) features and explore their significance in the immune microenvironment and chemotherapy resistance in STAD patients. By analyzing RNA sequencing and clinical data from STAD patients and extracting disulfidptosis-related genes, we identified DRLs through co-expression, single-factor and multi-factor Cox regression, and Lasso regression analyses. We also investigated differences in the immune microenvironment, immune function, immune checkpoint gene expression, and chemotherapy resistance between different risk groups using various algorithms. A prognostic risk model consisting of 2 DRLs was constructed, with a strong predictive value for patient survival, outperforming other clinical-pathological factors in predicting 3-year and 5-year survival. Immune-related analysis revealed a strong positive correlation between T cell CD4+ cells and risk score across all algorithms, and higher expression of immune checkpoint genes in the high-risk group. In addition, high-risk patients showed better sensitivity to Erlotinib, Oxaliplatin, and Gefitinib. Furthermore, three novel molecular subtypes of STAD were identified based on the 2-DRLs features, with evaluation of the immune microenvironment and chemotherapy drug sensitivity for each subgroup, which holds significant implications for achieving precise treatment in STAD. Overall, our 2-DRLs prognostic model demonstrates high predictive value for patient survival in STAD, potentially providing new targets for individualized immune and chemical therapy.

2X-Rhodamine: A Bright and Fluorogenic Scaffold for Developing Near-Infrared Chemigenetic Indicators.

Chemigenetic fusion of synthetic dyes with genetically encoded protein tags presents a promising avenue for in vivo imaging. However, its full potential has been hindered by the lack of bright and fluorogenic dyes operating in the "tissue transparency" near-infrared window (NIR, 700-1700 nm). Here, we report 2X-rhodamine (2XR), a novel bright scaffold that allows for the development of live-cell-compatible, NIR-excited variants with strong fluorogenicity beyond 1000 nm. 2XR utilizes a rigidified π-skeleton featuring dual atomic bridges and functions via a spiro-based fluorogenic mechanism. This design affords longer wavelengths, higher quantum yield (ΦF = 0.11), and enhanced fluorogenicity in water when compared to the phosphine oxide-cored, or sulfone-cored rhodamine, the NIR fluorogenic benchmarks currently used. We showcase their bright performance in video-rate dynamic imaging and targeted deep-tissue molecular imaging in vivo. Notably, we develop a 2XR variant, 2XR715-HTL, an NIR fluorogenic ligand for the HaloTag protein, enabling NIR genetically encoded calcium sensing and the first demonstration of in vivo chemigenetic labeling beyond 1000 nm. Our work expands the library of NIR fluorogenic tools, paving the way for in vivo imaging and sensing with the chemigenetic approach.

Insight into environmental adaptability of antibiotic resistome from surface water to deep sediments in anthropogenic lakes by metagenomics.

The escalating antibiotic resistance threatens the long-term global health. Lake sediment is a vital hotpot in transmitting antibiotic resistance genes (ARGs); however, their vertical distribution pattern and driving mechanisms in sediment cores remain unclear. This study first utilized metagenomics to reveal how resistome is distributed from surface water to 45 cm sediments in four representative lakes, central China. Significant vertical variations in ARG profiles were observed (R2 = 0.421, p < 0.001), with significant reductions in numbers, abundance, and Shannon index from the surface water to deep sediment (all p-values < 0.05). ARGs also has interconnections within the vertical profile of the lakes: twelve ARGs persistently exist all sites and depths, and shared ARGs (e.g., vanS and mexF) were assembled by diverse hosts at varying depths. The 0-18 cm sediment had the highest mobility and health risk of ARGs, followed by the 18-45 cm sediment and water. The drivers of ARGs transformed along the profile of lakes: microbial communities and mobile genetic elements (MGEs) dominated in water, whereas environmental variables gradually become the primary through regulating microbial communities and MGEs with increasing sediment depth. Interestingly, the stochastic process governed ARG assembly, while the stochasticity diminished under the mediation of Chloroflexi, Candidatus Bathyarcaeota and oxidation-reduction potential with increasing depth. Overall, we formulated a conceptual framework to elucidate the vertical environmental adaptability of resistome in anthropogenic lakes. This study shed on the resistance risks and their environmental adaptability from sediment cores, which could reinforce the governance of public health issues.

Photo-methanification of aquatic dissolved organic matters with different origins under aerobic conditions: Non-negligible role of hydroxyl radicals.

Lingering inconsistencies in the global methane (CH4) budget and ambiguity in CH4 sources and sinks triggered efforts to identify new CH4 formation pathways in natural ecosystems. Herein, we reported a novel mechanism of light-induced generation of hydroxyl radicals (•OH) that drove the production of CH4 from aquatic dissolved organic matters (DOMs) under ambient conditions. A total of five DOM samples with different origins were applied to examine their potential in photo-methanification production under aerobic conditions, presenting a wide range of CH4 production rates from 3.57 × 10-3 to 5.90 × 10-2 nmol CH4 mg-C-1 h-1. Experiments of •OH generator and scavenger indicated that the contribution of •OH to photo-methanificaiton among different DOM samples reached about 4∼42 %. In addition, Fourier transform infrared spectroscopy and Fourier transform ion cyclotron resonance mass spectrometry showed that the carbohydrate- and lipid-like substances containing nitrogen-bonded methyl groups, methyl ester, acetyl groups, and ketones, were the potential precursors for light-induced CH4 production. Based on the experimental results and simulated calculations, the contribution of photo-methanification of aquatic DOMs to the diffusive CH4 flux across the water-air interface in a typical eutrophic shallow lake (e.g., Lake Chaohu) ranged from 0.1 % to 18.3 %. This study provides a new perspective on the pathways of CH4 formation in aquatic ecosystems and a deeper understanding on the sources and sinks of global CH4.

[Land Change Simulation and Grassland Carbon Storage in the Loess Plateau Based on SSP-RCP Scenarios].

Exploring the spatial distribution of land use/coverage (LUCC) and ecosystem carbon reserves in the future of climate change can provide a scientific basis for optimizing the distribution of land resources and formulating social economic sustainable development policies. In this study, we integrated the plaques generating land use simulation (PLUS) model and ecosystem services and weighing comprehensive evaluation (InVEST) model. Based on the CMIP6-based sharing socio-economic path and representative concentration path (SSP-RCP), we evaluated the Loess Plateau for time and space dynamic changes in LUCC and ecosystem carbon reserves, analyzed the impact of driving factors on different regions, and explored the correlation between carbon reserves in various regions. The results showed:① In the future, the three scenarios were similar to the LUCC changes. The area of cultivated land, grassland, and unused land would be reduced to varying degrees, and the construction land had expanded sharply. The increase in the three scenarios was 29.23%-53.56% (SSP126), 34.59%-63.28% (SSP245), and 42.80%-73.27% (SSP585). ② Compared with that in 2020, the carbon reserves of SSP126 sites in 2040 increased by 1.813 8×106 t, and in the remaining scenarios it would continue to decline. By 2060, the grassland carbon reserves in the three scenarios decreased by 13.391×106, 33.548×106, and 85.871×106 t, respectively. ③ From the perspective of space correlation, the carbon reserves of the Loess Plateau were correlated between cities. The difference in future scenarios was not significant. The hotspots were distributed in the middle and north of the research area. There was no obvious cold spot area. ④ The changes in land use were predicted to increase or lose carbon reserves. Forestry, cultivated land, and grassland had more carbon reserves those in than other land types. Increasing their area and restrictions on the conversion of other land types should increase the ecosystem carbon reserves.

Molecular-Weight-Dependent Degradation of Plastics: Deciphering Host-Microbiome Synergy Biodegradation of High-Purity Polypropylene Microplastics by Mealworms.

The biodegradation of polypropylene (PP), a highly persistent nonhydrolyzable polymer, by Tenebrio molitor has been confirmed using commercial PP microplastics (MPs) (Mn 26.59 and Mw 187.12 kDa). This confirmation was based on the reduction of the PP mass, change in molecular weight (MW), and a positive Δδ13C in the residual PP. A MW-dependent biodegradation mechanism was investigated using five high-purity PP MPs, classified into low (0.83 and 6.20 kDa), medium (50.40 and 108.0 kDa), and high (575.0 kDa) MW categories to access the impact of MW on the depolymerization pattern and associated gene expression of gut bacteria and the larval host. The larvae can depolymerize/biodegrade PP polymers with high MW although the consumption rate and weight losses increased, and survival rates declined with increasing PP MW. This pattern is similar to observations with polystyrene (PS) and polyethylene (PE), i.e., both Mn and Mw decreased after being fed low MW PP, while Mn and/or Mw increased after high MW PP was fed. The gut microbiota exhibited specific bacteria associations, such as Kluyvera sp. and Pediococcus sp. for high MW PP degradation, Acinetobacter sp. for medium MW PP, and Bacillus sp. alongside three other bacteria for low MW PP metabolism. In the host transcriptome, digestive enzymes and plastic degradation-related bacterial enzymes were up-regulated after feeding on PP depending on different MWs. The T. molitor host exhibited both defensive function and degradation capability during the biodegradation of plastics, with high MW PP showing a relatively negative impact on the larvae.

Unlocking the potential: A novel prognostic index signature for acute myeloid leukemia.

Acute myeloid leukemia (AML) is an aggressive malignancy characterized by challenges in treatment, including drug resistance and frequent relapse. Recent research highlights the crucial roles of tumor microenvironment (TME) in assisting tumor cell immune escape and promoting tumor aggressiveness. This study delves into the interplay between AML and TME. Through the exploration of potential driver genes, we constructed an AML prognostic index (AMLPI). Cross-platform data and multi-dimensional internal and external validations confirmed that the AMLPI outperforms existing models in terms of areas under the receiver operating characteristic curves, concordance index values, and net benefits. High AMLPIs in AML patients were indicative of unfavorable prognostic outcomes. Immune analyses revealed that the high-AMLPI samples exhibit higher expression of HLA-family genes and immune checkpoint genes (including PD1 and CTLA4), along with lower T cell infiltration and higher macrophage infiltration. Genetic variation analyses revealed that the high-AMLPI samples associate with adverse variation events, including TP53 mutations, secondary NPM1 co-mutations, and copy number deletions. Biological interpretation indicated that ALDH2 and SPATS2L contribute significantly to AML patient survival, and their abnormal expression correlates with DNA methylation at cg12142865 and cg11912272. Drug response analyses revealed that different AMLPI samples tend to have different clinical selections, with low-AMLPI samples being more likely to benefit from immunotherapy. Finally, to facilitate broader access to our findings, a user-friendly and publicly accessible webserver was established and available at http://bioinfor.imu.edu.cn/amlpi. This server provides tools including TME-related AML driver genes mining, AMLPI construction, multi-dimensional validations, AML patients risk assessment, and figures drawing.

[Research progress on pathogenic mechanism of sepsis-induced liver injury and treatment with traditional Chinese medicine and its active components].

Sepsis is a systemic inflammatory response syndrome caused by infection, with high morbidity and mortality. Sepsis-induced liver injury(SILI) is one of the manifestations of sepsis-induced multiple organ syndrome. At present, there is no recommended pharmacological intervention for the treatment of SILI. traditional Chinese medicine(TCM), based on the holism and dialectical treatment concept, shows the therapeutic characteristics of multi-target and multi-pathway and can comprehensively prevent and treat SILI by interfering with inflammatory factors, inflammatory signaling pathways, and anti-oxidative stress and inhibiting apoptosis. This article reviewed the experimental studies on the treatment of SILI with TCM to clarify its pathogenic mechanism and therapeutic characteristics, so as to provide more ideas and directions for the development or preparation of new drugs.

Hollow Layered Iron-Based Prussian Blue Cathode with Reduced Defects for High-Performance Sodium-Ion Batteries.

Fe-based Prussian blue (Fe-PB) analogues have emerged as promising cathode materials for sodium-ion batteries, owing to their cost-effectiveness, high theoretical capacity, and environmental friendliness. However, their practical application is hindered by [Fe(CN)6] defects, negatively impacting capacity and cycle stability. This work reports a hollow layered Fe-PB composite material using 1,3,5-benzenetricarboxylic acid (BTA) as a chelating and etching agent by the hydrothermal method. Compared to benzoic acid, our approach significantly reduces defects and enhances the yield of Fe-PB. Notably, the hollow layered structure shortens the diffusion path of sodium ions, enhances the activity of low-spin Fe in the Fe-PB lattice, and mitigates volume changes during Na-ion insertion/extraction into/from Fe-PB. As a sodium-ion battery cathode, this hollow layered Fe-PB exhibits an impressive initial capacity of 95.9 mAh g-1 at a high current density of 1 A g-1. Even after 500 cycles, it still maintains a considerable discharge capacity of 73.1 mAh g-1, showing a significantly lower capacity decay rate (0.048%) compared to the control sample (0.089%). Moreover, the full cell with BTA-PB-1.6 as the cathode and HC as the anode provides a considerable energy density of 312.2 Wh kg-1 at a power density of 291.0 W kg-1. This research not only enhances the Na storage performance of Fe-PB but also increases the yield of products obtained by hydrothermal methods, providing some technical reference for the production of PB materials using the low-yield hydrothermal method.

The virtual staining method by quantitative phase imaging for label free lymphocytes based on self-supervised iteration cycle-consistent adversarial networks.

Quantitative phase imaging (QPI) provides 3D structural and morphological information for label free living cells. Unfortunately, this quantitative phase information cannot meet doctors' diagnostic requirements of the clinical "gold standard," which displays stained cells' pathological states based on 2D color features. To make QPI results satisfy the clinical "gold standard," the virtual staining method by QPI for label free lymphocytes based on self-supervised iteration Cycle-Consistent Adversarial Networks (CycleGANs) is proposed herein. The 3D phase information of QPI is, therefore, trained and transferred to a kind of 2D "virtual staining" image that is well in agreement with "gold standard" results. To solve the problem that unstained QPI and stained "gold standard" results cannot be obtained for the same label free living cell, the self-supervised iteration for the CycleGAN deep learning algorithm is designed to obtain a trained stained result as the ground truth for error evaluation. The structural similarity index of our virtual staining experimental results for 8756 lymphocytes is 0.86. Lymphocytes' area errors after converting to 2D virtual stained results from 3D phase information are less than 3.59%. The mean error of the nuclear to cytoplasmic ratio is 2.69%, and the color deviation from the "gold standard" is less than 6.67%.

Factors associated with damages and repair costs of reusable flexible bronchoscopes in pediatrics in China.

BACKGROUND: Frequent repairs of pediatric flexible bronchoscopes can lead to a huge financial burden for the hospital. This study aimed to investigate the common causes of the failures in pediatric flexible bronchoscopes and propose the measures to prevent the failures. METHODS: This was a retrospective study. We collected repair information of the pediatric flexible bronchoscopes reprocessed in the Department of Sterile Processing at a hospital between September 1, 2018 and September 1, 2022 in order to investigate the causes and possible factors associated with the failures in pediatric flexible bronchoscopes. RESULTS: The Department of Sterile Processing staff reprocessed the pediatric flexible bronchoscopes 4280 times. A total of 29 failures were identified. The failure rate was 0.678%. The average repair cost was USD7246.60. The common failures in the pediatric flexible bronchoscopes included dim video image, black dots, improper video image display or no image during angulation adjustment, and pressure marks in the insertion tube. The failure rates in flexible electronic bronchoscopes and small-diameter flexible bronchoscopes were 65.5% and 93.1%, respectively. The failure rate in the pediatric flexible bronchoscopes reprocessed by the staff members with less work experience was 75.9%. CONCLUSION: The failure rate in the pediatric flexible bronchoscopes was not high but the repair costs were extremely high. The types and size of the flexible bronchoscopes and work experience of the staff members responsible for bronchoscope reprocessing were the possible factors associated with the failure rate in the pediatric flexible bronchoscopes. It is advisable to further optimize the central workflow and management mode for reprocessing the pediatric flexible bronchoscopes, thereby extending their useful life and reducing costs.

Design, Synthesis, and Evaluation of [18F]BIBD-300 as a Positron Emission Tomography Tracer for Poly(ADP-Ribose) Polymerase-1.

Compounds 8a-j were designed to adjust the mode of interaction and lipophilicity of FTT by scaffold hopping and changing the length of the alkoxy groups. Compounds 8a, 8d, 8g, and BIBD-300 were screened for high-affinity PARP-1 through enzyme inhibition assays and are worthy of further evaluation. PET imaging of MCF-7 subcutaneous tumors with moderate expression of PARP-1 showed that compared to [18F]FTT, [18F]8a, [18F]8d, and [18F]8g exhibited greater nonspecific uptake, a lower target-to-nontarget ratio, and severe defluorination, while [18F]BIBD-300 exhibited lower nonspecific uptake and a greater target-to-nontarget ratio. PET imaging of 22Rv1 subcutaneous tumors, which highly express PARP-1, confirmed that the uptake of [18F]BIBD-300 in normal organs, such as the liver, muscle, and bone, was lower than that of [18F]FTT, and the ratio of tumor-to-muscle and tumor-to-liver [18F]BIBD-300 was greater than that of [18F]FTT. The biodistribution results in mice with MCF-7 and 22Rv1 subcutaneous tumors further validated the results of PET imaging. Unlike [18F]FTT, which mainly relies on hepatobiliary clearance, [18F]BIBD-300, which has lower lipophilicity, undergoes a partial shift from hepatobiliary to renal clearance, providing the possibility for [18F]BIBD-300 to indicate liver cancer. The difference in the PET imaging results for [18F]FTT, [18F]BIBD-300, and [18F]8j in 22Rv1 mice and the corresponding molecular docking results further confirmed that subtle structural modifications in lipophilicity greatly optimize the properties of the tracer. Cell uptake experiments also demonstrated that [18F]BIBD-300 has a high affinity for PARP-1. Metabolized and unmetabolized [18F]FTT and [18F]BIBD-300 were detected in the brain, indicating that they could not accurately quantify the amount of PARP-1 in the brain. However, PET imaging of glioma showed that both [18F]FTT and [18F]BIBD-300 could accurately localize both in situ to C6 and U87MG tumors. Based on its potential advantages in the diagnosis of breast cancer, prostate cancer, and glioma, as well as liver cancer, [18F]BIBD-300 is a new option for an excellent PARP-1 tracer.

SLAMF7 predicts prognosis and correlates with immune infiltration in serous ovarian carcinoma.

OBJECTIVE: Signaling lymphocytic activation molecule family members (SLAMFs) play a critical role in immune regulation of malignancies. This study aims to investigate the prognostic value and function of SLAMFs in ovarian cancer (OC). METHODS: The expression analysis of SLAMFs was conducted based on The Cancer Genome Atlas Ovarian Cancer Collection (TCGA-OV) and Gene Expression Omnibus (GEO) databases. Immunohistochemistry (IHC) was further performed on tissue arrays (n=98) to determine the expression of SLAMF7. Kaplan-Meier plotter and multivariate Cox regression model were used to evaluate the correlation of SLAMF7 expression with survival outcomes of patients. The molecular function of SLAMF7 in OC was further investigated using Gene Set Enrichment Analysis (GSEA). RESULTS: SLAMF7 mRNA expression were significantly upregulated in OC tumor tissue compared to normal tissue. IHC revealed that SLAMF7 expression was located in the interstitial parts of tumor tissue, and higher SLAMF7 expression was associated with favorable survival outcomes. GSEA demonstrated that SLAMF7 is involved immune-related pathways. Further analysis showed that SLAMF7 had a strong correlation with the T cell-specific biomarker (CD3) but not with the B cell (CD19, CD22, and CD23) and natural killer cell-specific biomarkers (CD85C, CD336, and CD337). Furthermore, IHC analysis confirmed that SLAMF7 was expressed in tumor-infiltrating T cells, and the IHC score of SLAMF7 was positively correlated with CD3 (r=0.85, p<0.001). CONCLUSION: SLAMF7 is expressed in the interstitial components of clinical OC tissue, and higher SLAMF7 expression indicated a favorable prognosis for patients with OC. Additionally, SLAMF7 is involved in T-cell immune infiltration in OC.

A Manganese-Based Nanodriver Coordinates Tumor Prevention and Suppression through STING Activation in Glioblastoma.

Glioblastoma (GBM), the most prevalent and aggressive primary malignant brain tumor, exhibits profound immunosuppression and demonstrates a low response rate to current immunotherapy strategies. Manganese cations (Mn2+) directly activate the cGAS/STING pathway and induce the unique catalytic synthesis of 2'3'-cGAMP to facilitate type I IFN production, thereby enhancing innate immunity. Here, a telodendrimer and Mn2+-based nanodriver (PLHM) with a small size is developed, which effectively target lymph nodes through the blood circulation and exhibit tumor-preventive effects at low doses of Mn2+ (3.7 mg kg-1). On the other hand, the PLHM nanodriver also exhibits apparent antitumor effects in GBM-bearing mice via inducing in vivo innate immune responses. The combination of PLHM with doxorubicin nanoparticles (PLHM-DOX NPs) results in superior inhibition of tumor growth in GBM-bearing mice due to the synergistic potentiation of STING pathway functionality by Mn2+ and the presence of cytoplasmic DNA. These findings demonstrate that PLHM-DOX NPs effectively stimulate innate immunity, promote dendritic cell maturation, and orchestrate cascaded infiltration of CD8 cytotoxic T lymphocytes within glioblastomas characterized by low immunogenicity. These nanodivers chelated with Mn2+ show promising potential for tumor prevention and antitumor effects on glioblastoma by activating the STING pathway.