Targeting miR-29 mitigates skeletal senescence and bolsters therapeutic potential of mesenchymal stromal cells.

Mesenchymal stromal cell (MSC) senescence is a key factor in skeletal aging, affecting the potential of MSC applications. Identifying targets to prevent MSC and skeletal senescence is crucial. Here, we report increased miR-29 expression in bone tissues of aged mice, osteoporotic patients, and senescent MSCs. Genetic overexpression of miR-29 in Prx1-positive MSCs significantly accelerates skeletal senescence, reducing cortical bone thickness and trabecular bone mass, while increasing femur cross-sectional area, bone marrow adiposity, p53, and senescence-associated secretory phenotype (SASP) levels. Mechanistically, miR-29 promotes senescence by upregulating p53 via targeting Kindlin-2 mRNA. miR-29 knockdown in BMSCs impedes skeletal senescence, enhances bone mass, and accelerates calvarial defect regeneration, also reducing lipopolysaccharide (LPS)-induced organ injuries and mortality. Thus, our findings underscore miR-29 as a promising therapeutic target for senescence-related skeletal diseases and acute inflammation-induced organ damage.

Unveiling novel double-negative prostate cancer subtypes through single-cell RNA sequencing analysis.

Recent advancements in single-cell RNA sequencing (scRNAseq) have facilitated the discovery of previously unrecognized subtypes within prostate cancer (PCa), offering new insights into cancer heterogeneity and progression. In this study, we integrated scRNAseq data from multiple studies, comprising publicly available cohorts and data generated by our research team, and established the Human Prostate Single cell Atlas (HuPSA) and Mouse Prostate Single cell Atlas (MoPSA) datasets. Through comprehensive analysis, we identified two novel double-negative PCa populations: KRT7 cells characterized by elevated KRT7 expression and progenitor-like cells marked by SOX2 and FOXA2 expression, distinct from NEPCa, and displaying stem/progenitor features. Furthermore, HuPSA-based deconvolution re-classified human PCa specimens, validating the presence of these novel subtypes. We then developed a user-friendly web application, "HuPSA-MoPSA" ( https://pcatools.shinyapps.io/HuPSA-MoPSA/ ), for visualizing gene expression across all newly established datasets. Our study provides comprehensive tools for PCa research and uncovers novel cancer subtypes that can inform clinical diagnosis and treatment strategies.

Serum uric acid, body mass index, and cardiovascular diseases: A multiple two-step Mendelian randomization study.

BACKGROUND AND AIMS: A number of health issues, including high serum uric acid (SUA) and cardiovascular disease (CVD), have been linked to obesity based on observational evidence, though it's currently unclear how these issues are causally related. In order to determine whether obesity mediates this association, we set out to investigate the causal relationship between SUA, obesity, and CVD. METHODS AND RESULTS: From publicly available genome-wide association studies, we acquired instrumental variables that had a strong correlation to SUA and body mass index (BMI). We employed multiple two-step Mendelian randomization (MR) analyses, using genetic and clinical data from various publicly available biological databases. The mediating role of BMI was examined through mediation analysis. SUA was genetically correlated with BMI [OR = 1.080, 95% CI: 1.024-1.139, P = 0.005]. There was a positive causal effect of SUA on AF [OR = 0.892, 95% CI: 0.804-0.990, P = 0.032], CAD [OR = 0.942, 95% CI: 0.890-0.997, P = 0.037], and EHT [OR = 1.080, 95% CI: 1.024-1.139, P = 0.005]. Among them, BMI mediated the effects of SUA on AF (42.2%; 95% CI, 35.3%-51.9%), CAD (76.3%; 95% CI, 63.4%-92.0%), and EHT (10.0%; 95% CI, 0%-20.0%). CONCLUSION: Our research revealed a causal relationship between high SUA exposure and an increased risk of obesity. Additionally, a high SUA level was linked to an increased risk of various CVDs. Given that individuals with high SUA are more likely to be susceptible to AF, CAD, and EHT, attention must be given to their weight status.

Predicting gastric cancer response to anti-HER2 therapy or anti-HER2 combined immunotherapy based on multi-modal data.

The sole use of single modality data often fails to capture the complex heterogeneity among patients, including the variability in resistance to anti-HER2 therapy and outcomes of combined treatment regimens, for the treatment of HER2-positive gastric cancer (GC). This modality deficit has not been fully considered in many studies. Furthermore, the application of artificial intelligence in predicting the treatment response, particularly in complex diseases such as GC, is still in its infancy. Therefore, this study aimed to use a comprehensive analytic approach to accurately predict treatment responses to anti-HER2 therapy or anti-HER2 combined immunotherapy in patients with HER2-positive GC. We collected multi-modal data, comprising radiology, pathology, and clinical information from a cohort of 429 patients: 310 treated with anti-HER2 therapy and 119 treated with a combination of anti-HER2 and anti-PD-1/PD-L1 inhibitors immunotherapy. We introduced a deep learning model, called the Multi-Modal model (MuMo), that integrates these data to make precise treatment response predictions. MuMo achieved an area under the curve score of 0.821 for anti-HER2 therapy and 0.914 for combined immunotherapy. Moreover, patients classified as low-risk by MuMo exhibited significantly prolonged progression-free survival and overall survival (log-rank test, P < 0.05). These findings not only highlight the significance of multi-modal data analysis in enhancing treatment evaluation and personalized medicine for HER2-positive gastric cancer, but also the potential and clinical value of our model.

Systematic Multi-Omics Investigation of Androgen Receptor Driven Gene Expression and Epigenetics changes in Prostate Cancer.

Background: Prostate cancer, a common malignancy, is driven by androgen receptor (AR) signaling. Understanding the function of AR signaling is critical for prostate cancer research. Methods: We performed multi-omics data analysis for the AR+, androgen-sensitive LNCaP cell line, focusing on gene expression (RNAseq), chromatin accessibility (ATACseq), and transcription factor binding (ChIPseq). High-quality datasets were curated from public repositories and processed using state-of-the-art bioinformatics tools. Results: Our analysis identified 1004 up-regulated and 707 down-regulated genes in response to androgen deprivation therapy (ADT) which diminished AR signaling activity. Gene-set enrichment analysis revealed that AR signaling influences pathways related to neuron differentiation, cell adhesion, P53 signaling, and inflammation. ATACseq and ChIPseq data demonstrated that as a transcription factor, AR primarily binds to distal enhancers, influencing chromatin modifications without affecting proximal promoter regions. In addition, the AR-induced genes maintained higher active chromatin states than AR-inhibited genes, even under ADT conditions. Furthermore, ADT did not directly induce neuroendocrine differentiation in LNCaP cells, suggesting a complex mechanism behind neuroendocrine prostate cancer development. In addition, a publicly available online application LNCaP-ADT (https://pcatools.shinyapps.io/shinyADT/) was launched for users to visualize and browse data generated by this study. Conclusion: This study provides a comprehensive multi-omics dataset, elucidating the role of AR signaling in prostate cancer at the transcriptomic and epigenomic levels. The reprocessed data is publicly available, offering a valuable resource for future prostate cancer research.

Long-term survivals of immune checkpoint inhibitors as neoadjuvant and adjuvant therapy in dMMR/MSI-H colorectal and gastric cancers.

BACKGROUND: The long-term survival benefit of immune checkpoint inhibitors (ICIs) in neoadjuvant and adjuvant settings is unclear for colorectal cancers (CRC) and gastric cancers (GC) with deficiency of mismatch repair (dMMR) or microsatellite instability-high (MSI-H). METHODS: This retrospective study enrolled patients with dMMR/MSI-H CRC and GC who received at least one dose of neoadjuvant ICIs (neoadjuvant cohort, NAC) or adjuvant ICIs (adjuvant cohort, AC) at 17 centers in China. Patients with stage IV disease were also eligible if all tumor lesions were radically resectable. RESULTS: In NAC (n = 124), objective response rates were 75.7% and 55.4%, respectively, in CRC and GC, and pathological complete response rates were 73.4% and 47.7%, respectively. The 3-year disease-free survival (DFS) and overall survival (OS) rates were 96% (95%CI 90-100%) and 100% for CRC (median follow-up [mFU] 29.4 months), respectively, and were 84% (72-96%) and 93% (85-100%) for GC (mFU 33.0 months), respectively. In AC (n = 48), the 3-year DFS and OS rates were 94% (84-100%) and 100% for CRC (mFU 35.5 months), respectively, and were 92% (82-100%) and 96% (88-100%) for GC (mFU 40.4 months), respectively. Among the seven patients with distant relapse, four received dual blockade of PD1 and CTLA4 combined with or without chemo- and targeted drugs, with three partial response and one progressive disease. CONCLUSION: With a relatively long follow-up, this study demonstrated that neoadjuvant and adjuvant ICIs might be both associated with promising DFS and OS in dMMR/MSI-H CRC and GC, which should be confirmed in further randomized clinical trials.

Modulate synthesis of CeMn solid solution using various alcohols for toluene catalytic oxidation: synergistic effect of Ce-Mn and reaction mechanism.

A redox co-precipitation method was employed to synthesize CeMn homogeneous solid solutions, utilizing various alcohols as activating agents. Ethanol effectively orchestrated the precipitation of CeO2 and MnOx, promoting their co-growth. As a result, the CeMn-EA achieved 90 % toluene conversion at 218 â„ƒ (T90 =218 â„ƒ) with a weight hourly space velocity (WHSV) of 48000 ml/(g·h). It also demonstrated high adaptability to increased WHSV, suggesting its potential for industrial-scale applications. The uniform dispersion of Ce and Mn accelerated the coupling between Ce3+/Ce4+ and Mn4+/Mn3+, engineering numerous oxygen vacancies, which enhanced the activation of gas-phase oxygen and the mobility of lattice oxygen. In situ DRIFTS confirmed that toluene oxidation accommodated both Langmuir-Hinshelwood (L-H) and Mars-van Krevelen (MvK) mechanisms, with benzoate identified as a pivotal intermediate. Enhanced oxygen mobility facilitated the cleavage of the benzene ring, which was the rate-determining step. Additionally, the introduction of H2O significantly enhanced the dissociation and adsorption of toluene and facilitated the activation of gas-phase oxygen. At higher temperatures, H2O could further activate lattice oxygen engaging in toluene oxidation. ENVIRONMENTAL IMPLICATION: Volatile organic compounds (VOCs) have emerged as major air pollutants due to the changes in air pollution patterns. They can act as precursors to near-surface ozone and haze. Toluene, a typical VOC, is primarily released from anthropogenic sources and poses significant risks to human health and the environment. Ce-based catalysts have been demonstrated efficiency in toluene oxidation due to their excellent oxygen storage and release properties. This study synthesized CeMn homogeneous solid solutions utilizing various alcohols as activating agents, which possessed abundant oxygen vacancies and optimum oxygen activation capacity to oxidize toluene in time.

Hemodynamics regulate spatiotemporal artery muscularization in the developing circle of Willis.

Vascular smooth muscle cells (VSMCs) envelop vertebrate brain arteries and play a crucial role in regulating cerebral blood flow and neurovascular coupling. The dedifferentiation of VSMCs is implicated in cerebrovascular disease and neurodegeneration. Despite its importance, the process of VSMC differentiation on brain arteries during development remains inadequately characterized. Understanding this process could aid in reprogramming and regenerating dedifferentiated VSMCs in cerebrovascular diseases. In this study, we investigated VSMC differentiation on zebrafish circle of Willis (CoW), comprising major arteries that supply blood to the vertebrate brain. We observed that arterial specification of CoW endothelial cells (ECs) occurs after their migration from cranial venous plexus to form CoW arteries. Subsequently, acta2+ VSMCs differentiate from pdgfrb+ mural cell progenitors after they were recruited to CoW arteries. The progression of VSMC differentiation exhibits a spatiotemporal pattern, advancing from anterior to posterior CoW arteries. Analysis of blood flow suggests that earlier VSMC differentiation in anterior CoW arteries correlates with higher red blood cell velocity and wall shear stress. Furthermore, pulsatile flow induces differentiation of human brain PDGFRB+ mural cells into VSMCs, and blood flow is required for VSMC differentiation on zebrafish CoW arteries. Consistently, flow-responsive transcription factor klf2a is activated in ECs of CoW arteries prior to VSMC differentiation, and klf2a knockdown delays VSMC differentiation on anterior CoW arteries. In summary, our findings highlight blood flow activation of endothelial klf2a as a mechanism regulating initial VSMC differentiation on vertebrate brain arteries.

Global burden of atrial fibrillation/atrial flutter and its attributable risk factors from 1990 to 2021.

AIMS: To devise effective preventive measures, a profound understanding of the evolving patterns and trends in atrial fibrillation (AF) and atrial flutter (AFL) burdens is pivotal. Our study was designed to quantify the burden and delineate the risk factors associated with AF and AFL across 204 countries and territories spanning 1990-2021. METHODS AND RESULTS: Data pertaining to AF and AFL were sourced from the Global Burden of Disease Study 2021. The burden of AF/AFL was evaluated using metrics such as incidence, disability-adjusted life years (DALYs), deaths, and their corresponding age-standardized rates (ASRs), stratified by age, sex, socio-demographic index (SDI), and human development index (HDI). The estimated annual percentage change was employed to quantify changes in ASRs. Population attributable fractions were calculated to determine the proportional contributions of major risk factors to age-standardized AF/AFL deaths. This analysis encompassed the period from 1990 to 2021. Globally, in 2021, there were 4.48 million incident cases [95% uncertainty interval (UI): 3.61-5.70], 8.36 million DALYs (95% UI: 6.97-10.13) and 0.34 million deaths (95% UI: 0.29-0.37) attributed to AF/AFL. The AF/AFL burden in 2021, as well as its trends from 1990 to 2021, displayed substantial variations based on gender, SDI quintiles, and geographical regions. High systolic blood pressure emerged as the leading contributor to age-standardized AF/AFL incidence, prevalence, death, and DALY rate globally among all potential risk factors, followed closely by high body mass index. CONCLUSION: Our study underscores the enduring significance of AF/AFL as a prominent public health concern worldwide, marked by profound regional and national variations. Despite the substantial potential for prevention and management of AF/AFL, there is a pressing imperative to adopt more cost-effective strategies and interventions to target modifiable risk factors, particularly in areas where the burden of AF/AFL is high or escalating.

Associations between specific volatile organic chemical exposures and cardiovascular disease risks: insights from NHANES.

Introduction: An increasing body of research has demonstrated a correlation between pollutants from the environment and the development of cardiovascular diseases (CVD). However, the impact of volatile organic chemicals (VOC) on CVD remains unknown and needs further investigation. Objectives: This study assessed whether exposure to VOC was associated with CVD in the general population. Methods: A cross-sectional analysis was conducted utilizing data from five survey cycles (2005-2006, 2011-2012, 2013-2014, 2015-2016, and 2017-2018) of the National Health and Nutrition Examination Survey (NHANES) program. We analyzed the association between urinary VOC metabolites (VOCs) and participants by multiple logistic regression models, further Bayesian Kernel Machine Regression (BKMR) models and Weighted Quantile Sum (WQS) regression were performed for mixture exposure analysis. Results: Total VOCs were found to be positively linked with CVD in multivariable-adjusted models (p for trend = 0.025), independent of established CVD risk variables, such as hypertension, diabetes, drinking and smoking, and total cholesterol levels. Compared with the reference quartile of total VOCs levels, the multivariable-adjusted odds ratios in increasing quartiles were 1.01 [95% confidence interval (CI): 0.78-1.31], 1.26 (95% CI: 1.05-1.21) and 1.75 (95% CI: 1.36-1.64) for total CVD. Similar positive associations were found when considering individual VOCs, including AAMA, CEMA, CYMA, 2HPMA, 3HPMA, IPM3 and MHBMA3 (acrolein, acrylamide, acrylonitrile, propylene oxide, isoprene, and 1,3-butadiene). In BKMR analysis, the overall effect of a mixture is significantly related to VOCs when all chemicals reach or exceed the 75th percentile. Moreover, in the WQS models, the most influential VOCs were found to be CEMA (40.30%), DHBMA (21.00%), and AMCC (19.70%). Conclusion: The results of our study indicated that VOC was all found to have a significant association with CVD when comparing results from different models. These findings hold significant potential for public health implications and offer valuable insights for future research directions.

Unveiling Novel Double-Negative Prostate Cancer Subtypes Through Single-Cell RNA Sequencing Analysis.

Recent advancements in single-cell RNA sequencing (scRNAseq) have facilitated the discovery of previously unrecognized subtypes within prostate cancer (PCa), offering new insights into disease heterogeneity and progression. In this study, we integrated scRNAseq data from multiple studies, comprising both publicly available cohorts and data generated by our research team, and established the HuPSA (Human Prostate Single cell Atlas) and the MoPSA (Mouse Prostate Single cell Atlas) datasets. Through comprehensive analysis, we identified two novel double-negative PCa populations: KRT7 cells characterized by elevated KRT7 expression, and progenitor-like cells marked by SOX2 and FOXA2 expression, distinct from NEPCa, and displaying stem/progenitor features. Furthermore, HuPSA-based deconvolution allowed for the re-classification of human PCa specimens, validating the presence of these novel subtypes. Leveraging these findings, we developed a user-friendly web application, "HuPSA-MoPSA" (https://pcatools.shinyapps.io/HuPSA-MoPSA/), for visualizing gene expression across all newly-established datasets. Our study provides comprehensive tools for PCa research and uncovers novel cancer subtypes that can inform clinical diagnosis and treatment strategies.

Ce-based three-dimensional mesoporous microspheres with Mn homogeneous incorporation for toluene oxidation.

Ce-based three-dimensional (3D) mesoporous microspheres with Mn homogeneous incorporation were synthesized. The CeMn-0.4, characterized by a Ce/Mn molar ratio of 6:4, demonstrated exceptional catalytic activity and stability. The formation of CeMn solid solution strengthened the Ce-Mn interaction, yielding higher concentrations of Ce3+ and Mn4+. Mn4+ initiated toluene preliminary activation owing to its robust oxidative properties, while Ce3+ contributed to oxygen vacancy generation, enhancing the activation of gaseous oxygen and lattice oxygen mobility. Integrating experiments and Density Functional Theory (DFT) calculations elucidated the oxygen reaction mechanisms. A portion of oxygen was converted into surface reactive oxygen species (Oads) that directly oxidized toluene. Additionally, the presence of oxygen vacancies promoted the participation of oxygen in toluene oxidation by converting it into lattice oxygen, which was crucial for the deep oxidation of toluene. Diffuse Reflectance Fourier Transform Infrared Spectroscopy (DRIFTS) indicated the accumulation of benzene-ring intermediates on the catalyst surface hindered continuous toluene oxidation. Thus, the abundant oxygen vacancies in CeMn-0.4 played a pivotal role in sustaining the oxidation process by bolstering the activation of gaseous oxygen and the mobility of lattice oxygen.

ZNF397 Deficiency Triggers TET2-Driven Lineage Plasticity and AR-Targeted Therapy Resistance in Prostate Cancer.

Cancer cells exhibit phenotypical plasticity and epigenetic reprogramming that allows them to evade lineage-dependent targeted treatments by adopting lineage plasticity. The underlying mechanisms by which cancer cells exploit the epigenetic regulatory machinery to acquire lineage plasticity and therapy resistance remain poorly understood. We identified zinc finger protein 397 (ZNF397) as a bona fide coactivator of the androgen receptor (AR), essential for the transcriptional program governing AR-driven luminal lineage. ZNF397 deficiency facilitates the transition of cancer cell from an AR-driven luminal lineage to a ten-eleven translocation 2 (TET2)-driven lineage plastic state, ultimately promoting resistance to therapies inhibiting AR signaling. Intriguingly, our findings indicate that a TET2 inhibitor can eliminate the resistance to AR-targeted therapies in ZNF397-deficient tumors. These insights uncover a novel mechanism through which prostate cancer acquires lineage plasticity via epigenetic rewiring and offer promising implications for clinical interventions designed to overcome therapy resistance dictated by lineage plasticity. Significance: This study reveals a bifurcated role of ZNF397, and a TET2-driven epigenetic mechanism regulating tumor lineage plasticity and therapy response in prostate cancer, enhances the understanding of drug resistance, and unveils a new therapeutic strategy for overcoming androgen receptor-targeted therapy resistance.

Targeting CXCR4/CXCL12 axis via [177Lu]Lu-DOTAGA.(SA.FAPi)2 with CXCR4 antagonist in triple-negative breast cancer.

PURPOSE: Radiopharmaceutical therapies targeting fibroblast activation protein (FAP) have shown promising efficacy against many tumor types. But radiopharmaceuticals alone in most cases are insufficient to completely eradicate tumor cells, which can partially be attributed to the protective interplay between tumor cells and cancer-associated fibroblasts (CAFs). The C-X-C chemokine receptor type 4/C-X-C motif chemokine 12 (CXCR4/CXCL12) interaction plays an important role in orchestrating tumor cells and CAFs. We hereby investigated the feasibility and efficacy of [177Lu]Lu-DOTAGA.(SA.FAPi)2, a FAP-targeting radiopharmaceutical, in combination with AMD3100, a CXCR4 antagonist, in a preclinical murine model of triple-negative breast cancer (TNBC). METHODS: Public database was first interrogated to reveal the correlation between CAFs' scores and the prognosis of TNBC patients, as well as the expression levels of FAP and CXCR4 in normal tissues and tumors. In vitro therapeutic efficacy regarding cell proliferation, migration, and colony formation was assessed in BALB/3T3 fibroblasts and 4T1 murine breast cancer cells. In vivo therapeutic efficacy was longitudinally monitored using serial 18F-FDG, [18F]AlF-NOTA-FAPI-04, and [68Ga]Ga-DOTA-Pentixafor PET/CT scans and validated using tumor sections through immunohistochemical staining of Ki-67, α-SMA, CXCR4, and CXCL12. Intratumoral abundance of myeloid-derived suppressive cells (MDSCs) was analyzed using flow cytometry in accordance with the PET/CT schedules. Treatment toxicity was evaluated by examining major organs including heart, lung, liver, kidney, and spleen. RESULTS: CAFs' scores negatively correlated with the survival of TNBC patients (p < 0.05). The expression of CXCR4 and FAP was both significantly higher in tumors than in normal tissues. The combination of [177Lu]Lu-DOTAGA.(SA.FAPi)2 and AMD3100 significantly suppressed cell proliferation, migration, and colony formation in cell culture, and exhibited synergistic effects in 4T1 tumor models along with a decreased number of MDSCs. PET/CT imaging revealed lowest tumor accumulation of 18F-FDG and [18F]AlF-NOTA-FAPI-04 on day 13 and day 14 after treatment started, both of which gradually increased at later time points. A similar trend was observed in the IHC staining of Ki-67, α-SMA, and CXCL12. CONCLUSION: The combination of [177Lu]Lu-DOTAGA.(SA.FAPi)2 and AMD3100 is a feasible treatment against TNBC with minimal toxicity in main organs.

The expression of PKM1 and PKM2 in developing, benign, and cancerous prostatic tissues.

Background: Neuroendocrine prostate cancer (NEPCa) is the most aggressive type of prostate cancer (PCa). However, energy metabolism, one of the hallmarks of cancer, in NEPCa has not been well studied. Pyruvate kinase M (PKM), which catalyzes the final step of glycolysis, has two main splicing isoforms, PKM1 and PKM2. The expression pattern of PKM1 and PKM2 in NEPCa remains unknown. Methods: In this study, we used immunohistochemistry, immunofluorescence staining, and bioinformatics analysis to examine the expression of PKM1 and PKM2 in mouse and human prostatic tissues. Results: We found that PKM2 was the predominant isoform expressed throughout prostate development and PCa progression, with slightly reduced expression in murine NEPCa. PKM1 was mostly expressed in stromal cells but low-level PKM1 was also detected in prostate basal epithelial cells. Its expression was absent in the majority of prostate adenocarcinoma (AdPCa) specimens but present in a subset of NEPCa. Additionally, we evaluated the mRNA levels of ten PKM isoforms that express exon 9 (PKM1-like) or exon 10 (PKM2-like). Some of these isoforms showed notable expression levels in PCa cell lines and human PCa specimens. Discussion: Our study characterized the expression pattern of PKM1 and PKM2 in prostatic tissues including developing, benign, and cancerous prostate. These findings lay the groundwork for understanding the metabolic changes in different PCa subtypes.

The regulation mechanism of transition metal doping on Hg0 adsorption and oxidation on Ce/TiO2(001) surface: A DFT study.

The mercury oxidation performance of Ce/TiO2 catalyst can be further enhanced by transition metal modifications. This study employed density functional theory (DFT) calculations to investigate the adsorption and oxidation mechanisms of Hg0 on Ce/TiO2(001) and its transition metal modified surfaces. According to the calculation results, Ru-, Mo-, Nb-, and Mn-doping increased the affinity of the Ce/TiO2(001) surface towards Hg0 and HCl, thereby facilitating the efficient capture and oxidation of Hg0. The increased adsorption energy (Eads) of the intermediate HgCl on the modified surfaces could promote its conversion to the final product HgCl2. The modification of transition metals impeded the desorption of the final products HgCl2 and HgO, but it did not serve as the rate-determining step. The oxidation of Hg0 by lattice oxygen and HCl followed the Mars-Maessen and Langmuir-Hinshelwood mechanisms, respectively. HCl exhibited higher mercury oxidation ability than lattice oxygen. The reactivity of lattice oxygen could be further improved by doping transition metals, their promotion order was Ru > Nb > Mo > Mn. In a HCl atmosphere, Mn modification could significantly reduce the energy barrier for HCl activation and HgCl2 formation, providing the optimal enhancement for the mercury oxidation ability of Ce/TiO2 catalyst. The screening method of transition metal modified components based on surface adsorption reaction and oxidation energy barrier was proposed in this study, which provided theoretical guidance for the development of CeTi based catalysts with high mercury oxidation activity.

Adaptation process of decellularized vascular grafts as hemodialysis access in vivo.

Arteriovenous grafts (AVGs) have emerged as the preferred option for constructing hemodialysis access in numerous patients. Clinical trials have demonstrated that decellularized vascular graft exhibits superior patency and excellent biocompatibility compared to polymer materials; however, it still faces challenges such as intimal hyperplasia and luminal dilation. The absence of suitable animal models hinders our ability to describe and explain the pathological phenomena above and in vivo adaptation process of decellularized vascular graft at the molecular level. In this study, we first collected clinical samples from patients who underwent the construction of dialysis access using allogeneic decellularized vascular graft, and evaluated their histological features and immune cell infiltration status 5 years post-transplantation. Prior to the surgery, we assessed the patency and intimal hyperplasia of the decellularized vascular graft using non-invasive ultrasound. Subsequently, in order to investigate the in vivo adaptation of decellularized vascular grafts in an animal model, we attempted to construct an AVG model using decellularized vascular grafts in a small animal model. We employed a physical-chemical-biological approach to decellularize the rat carotid artery, and histological evaluation demonstrated the successful removal of cellular and antigenic components while preserving extracellular matrix constituents such as elastic fibers and collagen fibers. Based on these results, we designed and constructed the first allogeneic decellularized rat carotid artery AVG model, which exhibited excellent patency and closely resembled clinical characteristics. Using this animal model, we provided a preliminary description of the histological features and partial immune cell infiltration in decellularized vascular grafts at various time points, including Day 7, Day 21, Day 42, and up to one-year post-implantation. These findings establish a foundation for further investigation into the in vivo adaptation process of decellularized vascular grafts in small animal model.

Analyzing the associations between tertiary lymphoid structures and postoperative prognosis, along with immunotherapy response in gastric cancer: findings from pooled cohort studies.

BACKGROUND: The clinical significance of tertiary lymphoid structure (TLS) in gastric cancer (GC) was uncertain. METHODS: A systematic search was performed in public databases for eligible studies as of April 2, 2023. Meta-analyses were performed to interrogate the associations between TLS levels and prognosis and immunotherapy response of GC. Bioinformatic analyses based on the nine-gene signature of TLS were further conducted to capture the biological underpinnings. RESULTS: Eleven studies containing 4224 GC cases were enrolled in the meta-analysis. TLS levels positively correlated with smaller tumor size, earlier T stage and N stage. Moreover, higher TLS levels were detected in diffuse and mix subtypes of GC (P < 0.001). Higher TLS levels strongly predicted favorable postoperative overall survival of GC, with HR of 0.36 (95%CI 0.26-0.50, P < 0.001) and 0.55 (95%CI 0.45-0.68, P < 0.001) of univariate and multivariate Cox analysis, respectively. Higher TLS levels were also in favor of the treatment response of anti-PD-1 inhibitors as later-line therapy of GC. TLS levels positively correlated with immune effector cells infiltration, diversity and richness of T cell receptor and B cell receptor repertoire, immune checkpoint genes expression, and immune-related genes mutation of GC in the TCGA-STAD cohort, representing higher immunogenicity and immunoactivity. Moreover, moderate accuracy of TLS levels in predicting benefit from anti-PD-1 inhibitors in the PRJEB25780 cohort was also validated (AUC 0.758, 95%CI 0.583-0.933), higher than the microsatellite instability-score and Epstein-Barr virus status. CONCLUSIONS: TLS levels demonstrated potential in predicting the postoperative prognosis and immunotherapy response of GC.

PCTA, a pan-cancer cell line transcriptome atlas.

A substantial volume of RNA sequencing data have been generated from cancer cell lines. However, it requires specific bioinformatics skills to compare gene expression levels across cell lines. This has hindered non-bioinformaticians from fully utilizing these valuable datasets in their research. To bridge this gap, we established a curated Pan-cancer Cell Line Transcriptome Atlas (PCTA) dataset. This resource aims to provide a user-friendly platform, allowing researchers without extensive bioinformatics expertise to access and leverage the wealth of information within the dataset for their studies. The PCTA dataset encompasses the expression matrix of 24,965 genes, featuring data from 84,385 samples derived from 5677 studies. This comprehensive compilation spans 535 cell lines, representing a spectrum of 114 cancer types originating from 30 diverse tissue types. On UMAP plots, cell lines originating from the same type of tissue tend to cluster together, illustrating the dataset's ability to capture biological relationships. Additionally, an interactive and user-friendly web application (https://pcatools.shinyapps.io/PCTA_app/) was developed for researchers to explore the PCTA dataset. This platform allows users to examine the expression of their genes of interest across a diverse array of samples.

Hepatic perivascular epithelioid cell tumor resembling hepatic adenoma and hepatocellular carcinoma on preoperative imaging: a case report.

Perivascular epithelioid cell tumor (PEComa), an uncommon mesenchymal neoplasm, arises from specialized perivascular epithelioid cells exhibiting distinct features of smooth muscle and melanocytic differentiation with unpredictable behavior. PEComa tends to occur more commonly in the uterus and kidneys; its occurrence in the liver is exceedingly rare. We presented a case of a 29-year-old woman with hepatic PEComa and evaluated the tumor with MRI, integrated 18F-fluorodeoxyglucose (FDG), and 68Ga-fibroblast activation protein inhibitor (FAPI) PET/CT scans at presentation. The patient had a history of intermittent utilization of oral contraceptive drugs for several years. An abdominal ultrasound in a physical examination from an outside institution revealed a mass in the liver. A contrast-enhanced abdominal MRI revealed restricted diffusion on diffusion-weighted imaging (DWI) and rapid contrast enhancement and washout patterns in the hepatic lesion, suggesting hepatic adenoma (HA) or hepatocellular carcinoma (HCC). Further assessment was carried out using 18F-FDG and 68Ga-FAPI PET/CT scans. The hepatic lesion was non-FDG avid, whereas increased tracer uptake was observed on the 68Ga-FAPI PET/CT. Subsequently, laparoscopic partial resection of liver segment V was performed. Immunohistochemical analyses demonstrated positive staining for HMB45, Melan-A, and SMA while showing negative results for AFP, glypican-3, hepatocyte, and arginase-1. The results were indicative of a hepatic PEComa diagnosis based on these findings. We also review the current literature on the clinical characteristics, pathological features, and challenges in the diagnosis of hepatic PEComa.