Associations between plasma markers and symptoms of anxiety and depression in patients with breast cancer.

BACKGROUND AND PURPOSE: Among patients with solid tumors, those with breast cancer (BC) experience the most severe psychological issues, exhibiting a high global prevalence of depression that negatively impacts prognosis. Depression can be easily missed, and clinical markers for its diagnosis are lacking. Therefore, this study in order to investigate the diagnostic markers for BC patients with depression and anxiety and explore the specific changes of metabolism. METHOD AND RESULTS: Thirty-eight BC patients and thirty-six matched healthy controls were included in the study. The anxiety and depression symptoms of the participants were evaluated by the 17-item Hamilton Depression Scale (HAMD-17) and Hamilton Anxiety Scale (HAMA). Plasma levels of glial fibrillary acidic protein (GFAP) and lipocalin-2 (LCN2) were evaluated using enzyme linked immunosorbent assay, and plasma lactate levels and metabolic characteristics were analyzed. CONCLUSION: This study revealed that GFAP and LCN2 may be good diagnostic markers for anxiety or depression in patients with BC and that plasma lactate levels are also a good diagnostic marker for anxiety. In addition, specific changes in metabolism in patients with BC were preliminarily explored.

Comparative benefits of Ki and SUV images in lesion detection during PET/CT imaging.

BACKGROUND: Clinical application of the tracer net influx rate (Ki) imaging in PET/CT remains limited, due to a lack of evidence demonstrating the superiority of Ki images in lesion detection, and guidelines on when to utilize Ki images. This study aims to compare the benefits of Ki and standardized uptake value (SUV) images in lesion detection during PET/CT imaging. By analyzing the performance of both techniques in identifying tumor lesions, the study seeks to provide guidance for the clinical application of Ki images. RESULTS: This retrospective study included 134 patients with 244 pathologically confirmed lesions (200 malignant and 44 benign). Patients with a histopathological diagnosis received a weight-based 18F-FDG injection and underwent 60-min total-body PET/CT dynamic imaging. SUV images were reconstructed using data collected from the last 10 min of the scans. Ki images were generated using the Patlak methods with data from minutes 12-60. The background SUVmax, SUVmean, SUVSD, Kimax, Kimean, and KiSD values were recorded. The signal-to-noise ratios of the SUV (SUVSNR) and Ki (KiSNR) images were calculated. The lesion detection rate and sensitivity of the SUV and Ki images were evaluated. The lesion-detection rates were 97.7% (214/219) and 99.5% (218/219) for the SUV and Ki images, respectively (p = .22). Five false-negative lesions on the SUV images were true-positive on the Ki images (3 hepatic malignancies and 2 metastatic lymph nodes). The sensitivity (94.0% vs. 96.0%, p = .22), specificity (41.9% vs. 41.9%, p > .99), accuracy (84.4% vs. 86.1%, p = .61), positive predictive value (87.9% vs. 88.1%, p = .94), negative predictive value (60.0% vs. 69.2%, p = .47), and the area under the curve [0.68 (95% confidence interval, 0.61-0.73) vs. 0.69 (95% confidence interval, 0.62-0.74)] were similar in the SUV and Ki images (all p ≥ .10). CONCLUSION: Ki images exhibit benefits in lesion detection compared to SUV images, particularly in organs with high background such as liver. The enhanced contrast provided by Ki imaging is recommended to clinically improve detection rates in such cases.

Pan-Cancer Screening and Validation of CALU's Role in EMT Regulation and Tumor Microenvironment in Triple-Negative Breast Cancer.

Purpose: Cancer-associated fibroblasts (CAFs) significantly contribute to tumor progression and the development of resistance to therapies across a range of malignancies, notably breast cancer. This study aims to elucidate the specific role and prognostic relevance of CALU across multiple cancer types. Patients and Methods: The association between CALU expression and prognosis, along with clinical characteristics in BRCA, HNSC, KIRP, LGG, and LIHC, was analyzed using data from the TCGA, GTEx, and GEO databases. Transcriptomic analysis of TCGA BRCA project data provided insights into the interaction between CALU and epithelial-mesenchymal transition (EMT) marker genes. Using TIMER and TISCH databases, the correlation between CALU expression and tumor microenvironment infiltration was assessed, alongside an evaluation of CALU expression across various cell types. Furthermore, CALU's influence on TNBC BRCA cell lines was explored, and its expression in tumor tissues was confirmed through immunohistochemical analysis of clinical samples. Results: This study revealed a consistent upregulation of CALU across several tumor types, including BRCA, KIRP, LIHC, HNSC, and LGG, with elevated CALU expression being associated with unfavorable prognoses. CALU expression was particularly enhanced in clinical contexts linked to poor outcomes. Genomic analysis identified copy number alterations as the principal factor driving CALU overexpression. Additionally, a positive correlation between CALU expression and CAF infiltration was observed, along with its involvement in the EMT process in both CAFs and malignant cells. In vitro experiments demonstrated that CALU is highly expressed in TNBC-BRCA cell lines, and knockdown of CALU effectively reversed EMT progression and inhibited cellular migration. Immunohistochemical analysis of clinical samples corroborated the elevated expression of CALU in tumors, along with alterations in EMT markers. Conclusion: This comprehensive pan-cancer analysis underscores CALU's critical role in modulating the tumor microenvironment and facilitating cell migration via the EMT pathway, identifying it as a potential therapeutic target.

LIG1 is a novel marker for bladder cancer prognosis: evidence based on experimental studies, machine learning and single-cell sequencing.

Background: Bladder cancer, a highly fatal disease, poses a significant threat to patients. Positioned at 19q13.2-13.3, LIG1, one of the four DNA ligases in mammalian cells, is frequently deleted in tumour cells of diverse origins. Despite this, the precise involvement of LIG1 in BLCA remains elusive. This pioneering investigation delves into the uncharted territory of LIG1's impact on BLCA. Our primary objective is to elucidate the intricate interplay between LIG1 and BLCA, alongside exploring its correlation with various clinicopathological factors. Methods: We retrieved gene expression data of para-carcinoma tissues and bladder cancer (BLCA) from the GEO repository. Single-cell sequencing data were processed using the "Seurat" package. Differential expression analysis was then performed with the "Limma" package. The construction of scale-free gene co-expression networks was achieved using the "WGCNA" package. Subsequently, a Venn diagram was utilized to extract genes from the positively correlated modules identified by WGCNA and intersect them with differentially expressed genes (DEGs), isolating the overlapping genes. The "STRINGdb" package was employed to establish the protein-protein interaction (PPI) network.Hub genes were identified through the PPI network using the Betweenness Centrality (BC) algorithm. We conducted KEGG and GO enrichment analyses to uncover the regulatory mechanisms and biological functions associated with the hub genes. A machine-learning diagnostic model was established using the R package "mlr3verse." Mutation profiles between the LIG1^high and LIG1^low groups were visualized using the BEST website. Survival analyses within the LIG1^high and LIG1^low groups were performed using the BEST website and the GENT2 website. Finally, a series of functional experiments were executed to validate the functional role of LIG1 in BLCA. Results: Our investigation revealed an upregulation of LIG1 in BLCA specimens, with heightened LIG1 levels correlating with unfavorable overall survival outcomes. Functional enrichment analysis of hub genes, as evidenced by GO and KEGG enrichment analyses, highlighted LIG1's involvement in critical function such as the DNA replication, cellular senescence, cell cycle and the p53 signalling pathway. Notably, the mutational landscape of BLCA varied significantly between LIG1high and LIG1low groups.Immune infiltrating analyses suggested a pivotal role for LIG1 in immune cell recruitment and immune regulation within the BLCA microenvironment, thereby impacting prognosis. Subsequent experimental validations further underscored the significance of LIG1 in BLCA pathogenesis, consolidating its functional relevance in BLCA samples. Conclusions: Our research demonstrates that LIG1 plays a crucial role in promoting bladder cancer malignant progression by heightening proliferation, invasion, EMT, and other key functions, thereby serving as a potential risk biomarker.

Identification of an Amino Acid Metabolism Reprogramming Signature for Predicting Prognosis, Immunotherapy Efficacy, and Drug Candidates in Colon Cancer.

Colon cancer ranked third among the most frequently diagnosed cancers worldwide. Amino acid metabolic reprogramming was related to the occurrence and development of colon cancer. We looked for the amino acid metabolism genes (AMGs) associated with amino acid metabolism from molecular signatures database as prognostic markers and constructed amino acid metabolism scoring model (AMS). According to AMS, the patients were divided into high AMS and low AMS groups, and the prognostic characteristics, molecular phenotypes, somatic cell mutation characteristics, immune cell infiltration characteristics, and immunotherapy effect of the two groups were systematically analyzed. Finally, the compounds targeting AMGs were also screened. We screen out 6 prognostic AMGs (P < 0.05) and construct an AMS model based on them. K-M curve indicated that OS in low AMS group was significantly higher than that in high group (P < 0.05), which were validated in multiple datasets. And different AMS groups had different molecular phenotypes, somatic cell mutation characteristics and immune cell infiltration characteristics. Low AMS group had a better effect for immunotherapy. In addition, we predicted potential therapeutic compounds that could bind to AMGs target proteins. AMS model can be used as a hierarchical tool to evaluate the prognosis, immune infiltration characteristics and immunotherapy response ability of colon cancer. And the compounds screened based on AMGs may become new anti-tumor drugs.

Laser-Generated Au nanoparticles as lithophilic sites in self-supported film host for anode-free lithium metal battery.

Anode-free lithium metal batteries (AFLMBs) are considered to have greater application potential than traditional LMBs because of their higher energy density and safety. Unfortunately, their poor cycling performances originated from the unsatisfactory reversibility of Li plating/stripping remains a big challenge. A rational designed host for lithium deposition is an effective solving strategy. Herein, pure Au nanoparticles (NPs) without any impurities are prepared by a liquid-phase laser irradiation technology to construct and develop a self-supported Au/reduced graphene oxide (Au/rGO) film as lithium deposition host for AFLMBs. The densely and uniformly distributed Au NPs provide abundant lithiophilic sites that significantly reduce the nucleation barrier of lithium. Attributed to the precise regulation of Au sites towards lithium nucleation/growth, dendrites-free anode and improved electrochemical performance are obtained by using the Au/rGO film host. It keeps stable for 30 min of lithiation at 6 mA cm-2 without dendrite formation. Additionally, the Li||Au/rGO half-cell shows an overpotential close to 0 mV and maintains a Coulombic efficiency exceeding 97 % after 500 cycles at 1 mA cm-2. Moreover, a symmetric Au/rGO-Li cell can operate for 700 h without short-circuit. When paired with LiFePO4 (LFP) to assemble a full battery, the Au/rGO-Li achieves 96 % capacity retention rate after 100 cycles. This work not only develops an efficient host for lithium, but also provides a unique strategy to the safety concerns associated with LMBs' anodes.

Facile fabrication of cedrol nanoemulsions with deep transdermal delivery ability and high safety for effective androgenic alopecia treatment.

The successful treatment of androgenic alopecia (AGA) hinges on an effective transdermal drug delivery strategy, a challenge that requires urgent attention. In this study, we introduce a novel approach utilizing cedrol nanoemulsions (CD-NEs) for AGA treatment. Our findings demonstrate that cedrol (CD) effectively inhibits the expression of 5α-reductase 2 (5αR2), akin to the FDA-approved drug finasteride, while also surpassing it in terms of promoting cell proliferation. Through formulation optimization, we have developed stable CD-NEs suitable for large-scale production. Experimental and molecular dynamics simulations further reveal that CD-NEs enhance transdermal penetration by altering lipid organization, facilitating CD delivery to deeper skin layers via a trans-epidermal pathway. In vivo studies conducted on AGA model C57BL/6 mice demonstrate that CD-NEs significantly promote hair follicle regeneration, accelerating the transition of hair follicles from the telogen phase to the anagen phase. Moreover, CD-NEs treatment leads to a significant reduction in dihydrotestosterone (DHT) levels in the skin while maintaining stasis levels in serum, underscoring its efficacy in targeting androgenetic pathways with high safety. This comprehensive analysis sheds light on the efficacy and mechanism of action of CD-NEs in hair regeneration, offering valuable insights for future clinical applications in AGA treatment.

Exploration the feasibility and additional value of [18F]FDG/[68Ga]Ga-FAPI-04 dual-low-activity-tracer one-stop total-body PET imaging at 34 min post-injection of [68Ga]Ga-FAPI-04.

OBJECTIVES: To validate the feasibility of one-stop 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) and [68Ga]Ga-fibroblast activation protein inhibitor-04 ([68Ga]Ga-FAPI-04) dual-low-activity-tracer positron emission tomography/computed tomography (PET/CT) at 34 min post-injection of [68Ga]Ga-FAPI-04 and explore its additional value. METHODS: Thirty pairs of patients with suspected malignancies who underwent dual-tracer imaging were enrolled in this retrospective study. The images were reconstructed at 34-39 and 50-60 min after additional injection of [68Ga]Ga-FAPI-04 (in one-stop FDG-FAPI PET/CT, named PETFDG, PETD34-39, and PETD50-60; in the 2-day protocol, named PETFDG', PETF34-39, and PETF50-60, respectively). Tumour-to-normal ratios (TNR) of lesions in PETFDG, PETD34-39, and PETD50-60 and TNR of lesions in PETF34-39 and PETF50-60 were evaluated separately. To evaluate the potential added value of one-stop FDG-FAPI PET/CT over the 2-day protocol, TNRs of PETFDG, PETD34-39, and PETD50-60 were compared with PETF34-39. The lesion detectability of the two imaging protocols was evaluated by chi-square test. RESULTS: Comparing FAPI-weighted PET (PETD34-39 and PETD50-60) and single-tracer imaging (PETFDG) in one-stop FDG-FAPI PET/CT, TNRs of FAPI-weighted PET were higher than those of PETFDG. PETD34-39 and PETD50-60 showed similar performance in lesion detectability and TNRs (all P > 0.05). In the 2-day protocol, there are no statistically significant differences in TNRs of all lesions at PETF34-39 and PETF50-60. Comparing one-stop FDG-FAPI PET/CT with the 2-day protocol, TNRs of PETF34-39 were significantly higher than those of PETFDG but lower than those of PETD34-39 and PETD50-60. Lesion detectability in the one-stop FDG-FAPI PET/CT was higher than that in the 2-day protocol. The average radiation dose in one-stop FDG-FAPI PET/CT was significantly lower than that in the 2-day protocol (P<0.001). CONCLUSION: One-stop FDG-FAPI PET/CT at 34 min could provide sufficient information to meet clinical diagnosis and showed better lesion detectability than that in the 2-day protocol.

Epigenetic clocks and gliomas: unveiling the molecular interactions between aging and tumor development.

Gliomas, the most prevalent and aggressive primary brain tumors, represent a diverse group of malignancies originating from glial cells. These tumors account for significant brain tumor-related morbidity and mortality, with higher incidence rates in North America and Europe compared to Asia and Africa. Genetic predispositions and environmental factors, particularly ionizing radiation, critically impact glioma risk. Epigenetics, particularly DNA methylation, plays a pivotal role in glioma research, with IDH-mutant gliomas showing aberrant methylation patterns contributing to tumorigenesis. Epigenetic clocks, biomarkers based on DNA methylation patterns predicting biological age, have revealed significant insights into aging and tumor development. Recent studies demonstrate accelerated epigenetic aging in gliomas, correlating with increased cancer risk and poorer outcomes. This review explores the mechanisms of epigenetic clocks, their biological significance, and their application in glioma research. Furthermore, the clinical implications of epigenetic clocks in diagnosing, prognosticating, and treating gliomas are discussed. The integration of epigenetic clock data into personalized medicine approaches holds promise for enhancing therapeutic strategies and patient outcomes in glioma treatment.

The interplay between metal ions and immune cells in glioma: pathways to immune escape.

This review explores the intricate roles of metal ions-iron, copper, zinc, and selenium-in glioma pathogenesis and immune evasion. Dysregulated metal ion metabolism significantly contributes to glioma progression by inducing oxidative stress, promoting angiogenesis, and modulating immune cell functions. Iron accumulation enhances oxidative DNA damage, copper activates hypoxia-inducible factors to stimulate angiogenesis, zinc influences cell proliferation and apoptosis, and selenium modulates the tumor microenvironment through its antioxidant properties. These metal ions also facilitate immune escape by upregulating immune checkpoints and secreting immunosuppressive cytokines. Targeting metal ion pathways with therapeutic strategies such as chelating agents and metalloproteinase inhibitors, particularly in combination with conventional treatments like chemotherapy and immunotherapy, shows promise in improving treatment efficacy and overcoming resistance. Future research should leverage advanced bioinformatics and integrative methodologies to deepen the understanding of metal ion-immune interactions, ultimately identifying novel biomarkers and therapeutic targets to enhance glioma management and patient outcomes.

SPECT/CT imaging: quantifying 99mTc-MDP concentration in the spine and pelvis.

OBJECTIVE: This study aimed to identify a relatively robust SUV for guiding clinical practice through quantitative measurement and comparison of various normalization methods based on the SUV of 99mTc-MDP in the normal spine and pelvis using an integrated SPECT/CT scanner. METHODS: Between June 2017 and September 2019, a total of 500 oncology patients (mean age, 60.9; men, 66.0%) who underwent bone SPECT/CT scans with 99mTc-MDP were enrolled in this retrospective study. The mean SUV (SUVmean) of 4962 spinal and pelvic bones was calculated based on the patients' body weight (BW), lean body mass (LBM), bone mineral content (BMC), body surface area (BSA), and body mass index (BMI), defined as SUVbw, SUVlbm, SUVbmc, SUVbsa, and SUVbmi, respectively. The coefficients of variation (CoVs) of the aforementioned parameters were compared, and the correlation and multiple linear regression analyses were used to compare the extent to which these parameters were affected by sex, age, height, weight, BMI, and CT values. RESULTS: The average SUVs in the normal spine and pelvis displayed a relatively wide variability: 4.573 ± 1.972 for SUVbw, 3.555 ± 1.517 for SUVlbm, 0.163 ± 0.071 for SUVbmc, 0.124 ± 0.052 for SUVbsa, and 1.668 ± 0.732 for SUVbmi. In general, SUVbsa had relatively lowest CoV (42.1%) in all vertebrae and pelvis compared with other SUVs. For correlation analyses, all SUVs displayed weak but significant correlations with age and CT values. For regression analyses, SUVbsa was influenced only by age, BMI, and CT values independently. The effects of these variables on SUVbsa were all smaller than those on conventional SUVbw. CONCLUSIONS: The SUVs of 99mTc-MDP in normal bone derived from quantitative bone SPECT/CT could serve as a reference for evaluating tumor bone metastasis, but it should be assessed on a site-specific basis. SUVbsa exhibited superior robustness among all the SUV normalization variations, indicating potential clinical applications.

Developing a Multifunctional Cathode for Photoassisted Lithium-Sulfur Battery.

Integration of solar cell and secondary battery cannot only promote solar energy application but also improve the electrochemical performance of battery. Lithium-sulfur battery (LSB) is an ideal candidate for photoassisted batteries owing to its high theoretical capacity. Unfortunately, the researches related the combination of solar energy and LSB are relatively lacking. Herein, a freestanding photoelectrode is developed for photoassisted lithium-sulfur battery (PALSB) by constructing a heterogeneous structured Au@N-TiO2 on carbon cloths (Au@N-TiO2/CC), which combines multiple advantages. The Au@N-TiO2/CC photoelectrode can produce the photoelectrons to facilitate sulfur reduction during discharge process, while generating holes to accelerate sulfur evolution during charge process, improving the kinetics of electrochemical reactions. Meanwhile, Au@N-TiO2/CC can work as an electrocatalyst to promote the conversion of intermediate polysulfides during charge/discharge process, mitigating induced side reactions. Benefiting from the synergistic effect of electrocatalysis and photocatalysis, PALSB assembled with an Au@N-TiO2/CC photoelectrode obtains ultrahigh specific capacity, excellent rate performance, and outstanding cycling performance. What is more, the Au@N-TiO2/CC assembled PALSB can be directly charged under light illumination. This work not only expands the application of solar energy but also provides a new insight to develop advanced LSBs.

Nischarin inhibits the epithelial-mesenchymal transition process and angiogenesis in breast cancer cells by inactivating FAK/ERK signaling pathway via EGF like repeats and discoidin domains 3.

BACKGROUND: Our previous study has demonstrated that Nischarin (NISCH) exerts its antitumor effects in breast cancer (BC) by suppressing cell migration and invasion. This study aims to explore the underlying mechanism through which NISCH functions in BC. METHODS AND RESULTS: The relevance between EGF Like Repeats and Discoidin Domains 3 (EDIL3) mRNA expression and the overall survival of tumor patients was depicted by the Kaplan-Meier curve. The findings revealed that overexpressed NISCH attenuated cell motility and colony-forming capacities of Hs578T cells, yet silenced NISCH in MDA-MB-231 cells led to contrasting results. Western blot (WB) analysis indicated that overexpression of NISCH significantly down-regulated the Vimentin and Slug expression, and inactivated the FAK/ERK signaling pathway. RNA sequencing (RNA-seq) was performed in NISCH-overexpressed Hs578T cells and the control cells to analyze differentially expressed genes (DeGs), and the results showed a significant down-regulation of EDIL3 mRNA level upon overexpression of NISCH. Subsequent functional analyses demonstrated that overexpression of EDIL3 attenuated the inhibitory effect of NISCH on cell migration, invasion, colony formation, and tube formation. CONCLUSION: In summary, our finding preliminarily revealed that NISCH inhibits the epithelial-mesenchymal transition (EMT) process and angiogenesis in BC cells by down-regulating EDIL3 to inactivate the FAK/ERK signaling pathway, thereby suppressing the progression of BC. Our results hold promise for contributing to the deep understanding of BC pathogenesis and identifying new therapeutic strategies for clinical application.

Enhancing electrochemical water-splitting efficiency with superaerophobic nickel-coated catalysts on Chinese rice paper.

The quest for efficient hydrogen production highlights the need for cost-effective and high-performance catalysts to enhance the electrochemical water-splitting process. A significant challenge in developing self-supporting catalysts lies in the high cost and complex modification of traditional substrates. In this study, we developed catalysts featuring superaerophobic microstructures engineered on microspherical nickel-coated Chinese rice paper (Ni-RP), chosen for its affordability and exceptional ductility. These catalysts, due to their microspherical morphology and textured surface, exhibited significant superaerophobic properties, substantially reducing bubble adhesion. The nickel oxy-hydroxide (NiOxHy) and phosphorus-doped nickel (PNi) catalysts on Ni-RP demonstrated effective roles in oxygen evolution reaction (OER) and hydrogen evolution reaction (HER), achieving overpotentials of 250 mV at 20 mA cm-2 and 87 mV at -10 mA cm-2 in 1 M KOH, respectively. Moreover, a custom water-splitting cell using PNi/Ni-RP and NiOxHy/Ni-RP electrodes reached an impressive average voltage of 1.55 V at 10 mA cm-2, with stable performance over 100 h in 1 M KOH. Our findings present a cost-effective, sustainable, and easily modifiable substrate that utilizes superaerophobic structures to create efficient and durable catalysts for water splitting. This work serves as a compelling example of designing high-performance self-supporting catalysts for electrocatalytic applications.

Potential of metallurgical iron-containing solid waste-based catalysts as activator of persulfate for organic pollutants degradation.

The production of solid wastes in the metallurgical industry has significant implications for land resources and environmental pollution. To address this issue, it is crucial to explore the potential of recycling these solid wastes to reduce land occupation while protecting the environment and promoting resource utilization. Steel slag, red mud, copper slag and steel picking waste liquor are examples of solid wastes generated during the metallurgical process that possess high iron content and Fe species, making them excellent catalysts for persulfate-based advanced oxidation processes (PS-AOPs). This review elucidates the catalytic mechanisms and pathways of Fe2+ and Fe0 in the activation PS. Additionally, it underscores the potential of metallurgical iron-containing solid waste (MISW) as a catalyst for PS activation, offering a viable strategy for its high-value utilization. Lastly, the article provides an outlook towards future challenges and prospects for MISW in PS activation for the degradation of organic pollutants.

Impact of Platelet-to-HDL-Cholesterol Ratio on Long-Term Mortality in Coronary Artery Disease Patients with or Without Type 2 Diabetes: Insights from a Chinese Multicenter Cohort.

Background: Inflammation contributes to the initiation and advancement of both coronary atherosclerosis and type 2 diabetes mellitus (T2DM). Recent evidence has underscored the platelet-to-HDL-cholesterol ratio (PHR) as a promising inflammatory biomarker closely linked to the severity of coronary artery disease (CAD). Nevertheless, the risk of adverse clinical outcomes remains unclear among CAD patients with varying PHR levels and glycemic status. Methods: A total of 56,316 CAD patients were enrolled, primarily focusing on mortality outcomes. Patients were categorized into four subgroups based on median baseline PHR values and glycemic status: lower PHR (PHR-L) and higher PHR (PHR-H) with or without T2DM. Cox proportional hazard model and subgroup analysis were employed to investigate the association between PHR and glycemic status with mortality. Results: Over a median 5.32-year follow-up, 8909 (15.8%) patients experienced all-cause mortality, with 3873 (6.9%) deaths attributed to cardiovascular causes. Compared to individuals in PHR-L/non-DM, those in PHR-H/non-DM, PHR-L/DM and PHR-H/DM groups exhibited a higher risk of all-cause death [adjusted hazard ratio (HR) 1.12, 95% confidence interval (CI) 1.06-1.18; HR 1.21, 95% CI 1.14-1.29; HR 1.43, 95% CI 1.34-1.52, respectively], as well as cardiac mortality [HR 1.19, 95% CI 1.08-1.30; HR 1.58, 95% CI 1.44-1.74; HR 1.89, 95% CI 1.72-2.07, respectively]. Cox proportional hazard model also revealed the highest mortality risk among patients in PHR-H/DM compared to other groups (P <0.05). Restricted cubic spline regression analysis revealed a positive linear association between PHR and all-cause as well as cardiac mortality (P for non-linearity >0.05) after adjustment. Additionally, subgroup analysis indicated consistent effects on cardiac mortality within diverse subsets. Conclusion: In this real-world observational cohort analysis, elevated PHR levels joint with T2DM were related to adverse long-term clinical outcomes in CAD patients. PHR levels may serve as a valuable tool for identifying high-risk individuals within this specific group. Trial Registration: The Cardiorenal ImprovemeNt II registry NCT05050877.

Apolipoprotein A-1 downregulation promotes basal-like breast cancer cell proliferation and migration associated with DNA methylation.

Apolipoprotein A-I (APOA1) performs different roles in different subtypes of breast cancer. It is hypothesized to function as a tumor suppressor in basal-like breast cancer (BLBC). However, the specific role of APOA1 in BLBC and its underlying mechanisms remain unknown. The findings of the present study demonstrated a positive correlation between the expression level of APOA1 and the overall survival of patients with BLBC. Ectopic expression of APOA1 effectively inhibits the proliferation and metastasis of BLBC cells in vitro, and these effects are closely related to DNA methylation. To the best of our knowledge, the present study is the first to report increased methylation of the promoter region and decreased methylation of the structural genes of APOA1 in BLBC cells. These alterations resulted in the downregulation of APOA1 expression and suppression of BLBC tumor growth. Collectively, the results of the present study suggested that APOA1 mRNA expression is negatively regulated by DNA methylation in BLBC. Therefore, low expression of APOA1 may be a potential risk biomarker to predict survival in patients with BLBC.

Disparities in quality of life among patients with breast cancer based on surgical methods: a cross-sectional prospective study.

To determine the impact of breast conservation on quality of life and identify treatment-related and other demographic factors associated with post-breast cancer treatment quality of life. A prospective study was conducted on 392 women who underwent breast cancer surgery at Hangzhou Cancer Hospital from January 1, 2013, to December 31, 2022. Operable breast cancer patients who had completed all treatments except endocrine therapy were included. Patients with tumor recurrence/metastasis, bilateral or male breast cancer, and other primary malignancies were excluded. After enrollment, patients were asked to complete the BREAST-Q scale, and their pathological and medical records were reviewed. Analysis of variance was used to compare the quality of life scores among the groups. Univariate and multivariate linear regression analyses were performed to identify independent factors associated with quality of life scores in different domains. Participants completed the BREAST-Q scale at a median of 4.6 years after surgery. Quality of life scores varied based on the therapeutic strategy. Breast conservation has significant advantages over mastectomy in terms of breast satisfaction, psychosocial, and sexual well-being. Compared to oncoplastic breast-conserving surgery, mastectomy was independently associated with decreased breast satisfaction, psychosocial, and sexual well-being, while conventional breast-conserving surgery showed comparable outcomes to oncoplastic breast-conserving surgery in terms of these factors. Breast conservation leads to an improvement in quality of life compared to mastectomy. Oncoplastic breast-conserving surgery does not lead to a decrease in quality of life compared to conventional breast-conserving surgery and offers better outcomes compared to mastectomy.

Defect Engineering of Hexagonal MAB Phase Ti2InB2 as Anode of Lithium-Ion Battery with Excellent Cycling Stability.

Hexagonal MAB phases （h-MAB） have attracted attention due to their potential to exfoliate into MBenes, similar to MXenes, which are predicted to be promising for Li-ion battery applications. However, the high cost of synthesizing MBenes poses challenges for their use in batteries. This study presents a novel approach where a simple ball-milling treatment is employed to enhance the purity of the h-MAB phase Ti2InB2 and introduce significant indium defects, resulting in improved conductivity and the creation of abundant active sites. The synthesized Ti2InB2 with indium defects (VIn-Ti2InB2) exhibits excellent electrochemical properties, particularly exceptional long-cycle stability at current densities of 5 A g-1 (5000 cycles, average capacity decay of 0.0018%) and 10 A g-1 (15 000 cycles, average capacity decay of 0.093%). The charge storage mechanism of VIn-Ti2InB2, involving a dual redox reaction, is proposed, where defects promote the In-Li alloy reaction and a redox reaction with Li in the TiB layer. Finally, a Li-ion full cell demonstrates cycling stability at 0.5 A g-1 after 350 cycles. This work presents the first accessible and scalable application of VIn-Ti2InB2 as a Li-ion anode, unlocking a wealth of possibilities for sustainable electrochemical applications of h-MAB phases.

Shift in perspective: autoimmunity protecting against rheumatoid arthritis.

A hallmark of rheumatoid arthritis (RA) is the increased levels of autoantibodies preceding the onset and contributing to the classification of the disease. These autoantibodies, mainly anti-citrullinated protein antibody (ACPA) and rheumatoid factor, have been assumed to be pathogenic and many attempts have been made to link them to the development of bone erosion, pain and arthritis. We and others have recently discovered that most cloned ACPA protect against experimental arthritis in the mouse. In addition, we have identified suppressor B cells in healthy individuals, selected in response to collagen type II, and these cells decrease in numbers in RA. These findings provide a new angle on how to explain the development of RA and maybe also other complex autoimmune diseases preceded by an increased autoimmune response.