Influence of H19 polymorphisms on breast cancer: risk assessment and prognostic implications via LincRNA H19/miR-675 and downstream pathways.

Introduction: Breast cancer, as the most prevalent malignancy among women globally, continues to exhibit rising incidence rates, particularly in China. The disease predominantly affects women aged 40 to 60 and is influenced by both genetic and environmental factors. This study focuses on the role of H19 gene polymorphisms, investigating their impact on breast cancer susceptibility, clinical outcomes, and response to treatment. Methods: We engaged 581 breast cancer patients and 558 healthy controls, using TaqMan assays and DNA sequencing to determine genotypes at specific loci (rs11042167, rs2071095, rs2251375). We employed in situ hybridization and immunohistochemistry to measure the expression levels of LincRNA H19, miR-675, MRP3, HOXA1, and MMP16 in formalin-fixed, paraffin-embedded samples. Statistical analyses included chi-squared tests, logistic regression, and Kaplan-Meier survival curves to evaluate associations between genetic variations, gene expression, and clinical outcomes. Results: Genotypes AG at rs11042167, GT at rs2071095, and AC at rs2251375 were significantly associated with increased risk of breast cancer. Notably, the AA genotype at rs11042167 and TT genotype at rs2071095 were linked to favorable prognosis. High expression levels of LincRNA H19, miR-675, MRP3, HOXA1, and MMP16 in cancer tissues correlated with advanced disease stages and poorer survival rates. Spearman correlation analysis revealed significant positive correlations between the expression of LincRNA H19 and miR-675 and specific genotypes, highlighting their potential regulatory roles in tumor progression. Discussion: The study underscores the critical roles of LincRNA H19 and miR-675 as prognostic biomarkers in breast cancer, with their overexpression associated with disease progression and adverse outcomes. The H19/LincRNA H19/miR-675/MRP3-HOXA1-MMP16 axis offers promising targets for new therapeutic strategies, reflecting the complex interplay between genetic markers and breast cancer pathology. Conclusion: The findings confirm that certain H19 SNPs are associated with heightened breast cancer risk and that the expression profiles of related genetic markers can significantly influence prognosis and treatment response. These biomarkers hold potential as targets for personalized therapy and early detection strategies in breast cancer, underscoring the importance of genetic research in understanding and managing this disease.

Investigation of tumour environments through advancements in microtechnology and nanotechnology.

Cancer has a significant negative social and economic impact on both developed and developing countries. As a result, understanding the onset and progression of cancer is critical for developing therapies that can improve the well-being and health of individuals with cancer. With time, study has revealed, the tumor microenvironment has great influence on this process. Micro and nanoscale engineering techniques can be used to study the tumor microenvironment. Nanoscale and Microscale engineering use Novel technologies and designs with small dimensions to recreate the TME. Knowing how cancer cells interact with one another can help researchers develop therapeutic approaches that anticipate and counteract cancer cells' techniques for evading detection and fighting anti-cancer treatments, such as microfabrication techniques, microfluidic devices, nanosensors, and nanodevices used to study or recreate the tumor microenvironment. Nevertheless, a complicated action just like the growth and in cancer advancement, and their intensive association along the environment around it that has to be studied in more detail.

Evaluation of the value of Synechococcus 7942 as a sensitizer for photo-sonodynamic therapy against breast cancer.

This study was conducted to investigate the value of Synechococcus 7942 (Syne) as a sensitizer for photo-sonodynamic therapy (PSDT). Syne was characterized. The efficacy of Syne-mediated PSDT were verified in vitro (in 4T1 breast cancer cells) and in vivo (in a breast tumor-bearing mouse model). The safety of Syne-mediated PSDT was verified in vivo. Results indicated that Syne triggered the generation of oxygen and ROS during PSDT, thereby inducing cell death in 4T1 cells. Syne-mediated PSDT induced the death of tumor cells both in vitro and in vivo. The speed of tumor growth was delayed in animals receiving PSDT. Syne-mediated PSDT was more effective than photodynamic therapy or sonodynamic therapy alone. In addition, administration of a Syne monomer resulted in satisfactory tumor targeting. Syne-mediated PSDT affected neither the animal body weight nor the major organs, indicating satisfactory safety. Accordingly, Syne is an efficient, safe, and readily available sensitizer that is ideal for potential clinical use of PSDT to treat breast cancer. The findings of this study are useful for exploration of a novel sensitizer for PSDT, which might be a promising alternative therapy against breast cancer.

Spatial position changes in the semicircular canals may be the anatomical basis of Meniere's disease: a preliminary study based on ultra-high-resolution computed tomography (CT) and intelligent segmentation.

Background: Meniere's disease (MD) is an ear-related vestibular disorder accompanied by vertigo, hearing loss, and tinnitus. The anatomical structure and spatial position of the semicircular canals are important for understanding vestibular function and disease; however, research on MD and the effect of anatomical changes in the semicircular canals is limited. This study explored the relationship between the spatial location of the semicircular canals and MD using ultra-high-resolution computed tomography (U-HRCT) and intelligent segmentation. Methods: Isotropic U-HRCT images obtained from patients with MD and healthy controls (HCs) were retrospectively analyzed. We extracted the semicircular canal structures and extracted their skeleton. The plane of the skeleton of each semicircular canal was fitted separately. The mutual angles between the semicircular canals, and the angles between each semicircular canal and each plane of the coordinate system were measured. Results: Among 45 MD-affected ears (MDAEs), 33 MD-healthy ears (MDHEs), and 45 HC ears, the angle between the superior and lateral semicircular canals (LSCs) and the angle between the superior and posterior semicircular canals (PSCs) were larger in the MDAE and MDHE groups than the HC group (P<0.01), while the angle between the posterior and LSCs was smaller in the MDAE group than the HC group (P<0.001). The angles between the superior and PSCs and coronal plane (CP) of the coordinate system were significantly smaller in the MDAE and MDHE groups than the HC group (P<0.01); however, the angles between the LSC and axial plane and CP were significantly larger in the MDAE and MDHE groups than the HC group (P<0.001). Conclusions: Spatial position changes in the semicircular canals may be the anatomical basis of MD.

The YY1-CPT1C signaling axis modulates the proliferation and metabolism of pancreatic tumor cells under hypoxia.

Carnitine palmitoyltransferase 1C (CPT1C) is an enzyme that regulates tumor cell proliferation and metabolism by modulating mitochondrial function and lipid metabolism. Hypoxia, commonly observed in solid tumors, promotes the proliferation and progression of pancreatic cancer by regulating the metabolic reprogramming of tumor cells. So far, the metabolic regulation of hypoxic tumor cells by CPT1C and the upstream mechanisms of CPT1C remain poorly understood. Yin Yang 1 (YY1) is a crucial oncogene for pancreatic tumorigenesis and acts as a transcription factor that is involved in multiple metabolic processes. This study aimed to elucidate the relationship between YY1 and CPT1C under hypoxic conditions and explore their roles in hypoxia-induced proliferation and metabolic alterations of tumor cells. The results showed enhancements in the proliferation and metabolism of PANC-1 cells under hypoxia, as evidenced by increased cell growth, cellular ATP levels, up-regulation of mitochondrial membrane potential, and decreased lipid content. Interestingly, knockdown of YY1 or CPT1C inhibited hypoxia-induced rapid cell proliferation and vigorous cell metabolism. Importantly, for the first time, we reported that YY1 directly activated the transcription of CPT1C and clarified that CPT1C was a novel target gene of YY1. Moreover, the YY1 and CPT1C were found to synergistically regulate the proliferation and metabolism of hypoxic cells through transfection with YY1 siRNA to CRISPR/Cas9-CPT1C knockout PANC-1 cells. Taken together, these results indicated that the YY1-CPT1C axis could be a new target for the intervention of pancreatic cancer proliferation and metabolism.

Multimorbidity measures associated with cognitive function among community-dwelling older Chinese adults.

INTRODUCTION: Older adults with multimorbidity are at high risk of cognitive impairment development. There is a lack of research on the associations between different multimorbidity measures and cognitive function among older Chinese adults living in the community. METHODS: We used the Chinese Longitudinal Healthy Longevity Survey from 2002 to 2018 and included data on dementia-free participants aged ≥65 years. Multimorbidity measures included condition counts, multimorbidity patterns, and trajectories. The association of multimorbidity measures with cognitive function was examined by generalized estimating equation and linear and logistic regression models. RESULTS: Among 14,093 participants at baseline, 43.2% had multimorbidity. Multimorbidity patterns were grouped into cancer-inflammatory, cardiometabolic, and sensory patterns. Multimorbidity trajectories were classified as "onset-condition," "newly developing," and "severe condition." The Mini-Mental State Examination scores were significantly lower for participants with more chronic conditions, with cancer-inflammatory/cardiometabolic/sensory patterns, and with developing multimorbidity trajectories. DISCUSSION: Condition counts, sensory pattern, cardiometabolic pattern, cancer-inflammatory pattern, and multimorbidity developmental trajectories were prospectively associated with cognitive function. HIGHLIGHTS: Elderly individuals with a higher number of chronic conditions were associated with lower MMSE scores in the Chinese Longitudinal Healthy Longevity Survey data. MMSE scores were significantly lower for participants with specific multimorbidity patterns. Individuals with developing trajectories of multimorbidity were associated with lower MMSE scores and a higher risk of mild cognitive impairment.

OTUB2 silencing promotes ovarian cancer via mitochondrial metabolic reprogramming and can be synthetically targeted by CA9 inhibition.

Ovarian cancer is an aggressive gynecological tumor characterized by a high relapse rate and chemoresistance. Ovarian cancer exhibits the cancer hallmark of elevated glycolysis, yet effective strategies targeting cancer cell metabolic reprogramming to overcome therapeutic resistance in ovarian cancer remain elusive. Here, we revealed that epigenetic silencing of Otubain 2 (OTUB2) is a driving force for mitochondrial metabolic reprogramming in ovarian cancer, which promotes tumorigenesis and chemoresistance. Mechanistically, OTUB2 silencing destabilizes sorting nexin 29 pseudogene 2 (SNX29P2), which subsequently prevents hypoxia-inducible factor-1 alpha (HIF-1α) from von Hippel-Lindau tumor suppressor-mediated degradation. Elevated HIF-1α activates the transcription of carbonic anhydrase 9 (CA9) and drives ovarian cancer progression and chemoresistance by promoting glycolysis. Importantly, pharmacological inhibition of CA9 substantially suppressed tumor growth and synergized with carboplatin in the treatment of OTUB2-silenced ovarian cancer. Thus, our study highlights the pivotal role of OTUB2/SNX29P2 in suppressing ovarian cancer development and proposes that targeting CA9-mediated glycolysis is an encouraging strategy for the treatment of ovarian cancer.

The risk of endocrine immune-related adverse events induced by PD-1 inhibitors in cancer patients: a systematic review and meta-analysis.

Objective: Endocrinopathies are the most common immune-related adverse events (irAEs) observed during therapy with PD-1 inhibitors. In this study, we conducted a comprehensive systematic review and meta-analysis to evaluate the risk of immune-related endocrinopathies in patients treated with PD-1 inhibitors. Methods: We performed a systematic search in the PubMed, Embase, and Cochrane Library databases to retrieve all randomized controlled trials (RCTs) involving PD-1 inhibitors, spanning from their inception to November 24, 2023. The comparative analysis encompassed patients undergoing chemotherapy, targeted therapy, or receiving placebo as control treatments. This study protocol has been registered with PROSPERO (CRD42023488303). Results: A total of 48 clinical trials comprising 24,514 patients were included. Compared with control groups, patients treated with PD-1 inhibitors showed an increased risk of immune-related adverse events, including hypothyroidism, hyperthyroidism, hypophysitis, thyroiditis, diabetes mellitus, and adrenal insufficiency. Pembrolizumab was associated with an increased risk of all aforementioned endocrinopathies (hypothyroidism: RR=4.76, 95%CI: 3.55-6.39; hyperthyroidism: RR=9.69, 95%CI: 6.95-13.52; hypophysitis: RR=5.47, 95%CI: 2.73-10.97; thyroiditis: RR=5.95, 95%CI: 3.02-11.72; diabetes mellitus: RR=3.60, 95%CI: 1.65-7.88; adrenal insufficiency: RR=4.80, 95%CI: 2.60-8.88). Nivolumab was associated with an increased risk of hypothyroidism (RR=7.67, 95%CI: 5.00-11.75) and hyperthyroidism (RR=9.22, 95%CI: 4.71-18.04). Tislelizumab and sintilimab were associated with an increased risk of hypothyroidism (RR=19.07, 95%CI: 5.46-66.69 for tislelizumab and RR=18.36, 95%CI: 3.58-94.21 for sintilimab). For different tumor types, both hypothyroidism and hyperthyroidism were at high risks. Besides, patients with non-small cell lung cancer were at a higher risk of thyroiditis and adrenal insufficiency. Patients with melanoma were at a higher risk of hypophysitis and diabetes mellitus. Both low- and high-dose group increased risks of hypothyroidism and hyperthyroidism. Conclusion: Risk of endocrine irAEs may vary in different PD-1 inhibitors and different tumor types. Increased awareness and understanding of the risk features of endocrine irAEs associated with PD-1 inhibitors is critical for clinicians. Systematic review registration: crd.york.ac.uk/prospero, identifier PROSPERO (CRD42023488303).

Differences in the intestinal microbiota and association of host metabolism with hair coat status in cattle.

Introduction: The hair coat status of cattle serves as an easily observed indicator of economic value in livestock production; however, the underlying mechanism remains largely unknown. Therefore, the objective of the current study was to determine differences in the intestinal microbiota and metabolome of cattle based on a division of with either slick and shining (SHC) or rough and dull (MHC) hair coat in Simmental cows. Methods: Eight SHC and eight MHC late-pregnancy Simmental cows (with similar parities, body weights, and body conditions) were selected based on their hair coat status, and blood samples (plasma) from coccygeal venipuncture and fecal samples from the rectum were collected. The intestinal microbiota (in the fecal samples) was characterized by employing 16S rRNA gene sequencing targeting the V3-V4 hypervariable region on the Illumina MiSeq PE300 platform, and plasma samples were subjected to LC-MS/MS-based metabolomics with Progenesis QI 2.3. Plasma macromolecular metabolites were examined for differences in the metabolism of lipids, proteins, mineral elements, and hormones. Results: Notable differences between the SHC and MHC groups related to host hair coat status were observed in the host metabolome and intestinal microbiota (P < 0.05). The host metabolome was enriched in histidine metabolism, cysteine and methionine metabolism, and purine metabolism in the SHC group, and the intestinal microbiota were also enriched in histidine metabolism (P < 0.05). In the MHC group, the symbiotic relationship transitioned from cooperation to competition in the MHC group, and an uncoupling effect was present in the microbe-metabolite association of intestine microbiota-host interactions. The hubs mediating the relationships between intestinal microbiota and plasma metabolites were the intestinal bacterial genus g__norank_f__Eubacterium_coprostanoligenes_group, plasma inosine, triiodothyronine, and phosphorus, which could be used to differentiate cows' hair coat status (P < 0.05). Conclusion: Overall, the present study identified the relationships between the features of the intestinal microbiota and host hair coat status, thereby providing evidence and a new direction (intestine microbiota-host interplay) for future studies aimed at understanding the hair coat status of cattle.

Integrative analysis unveils ECM signatures and pathways driving hepatocellular carcinoma progression: A multi-omics approach and prognostic model development.

Liver hepatocellular carcinoma (LIHC) is a highly lethal form of cancer that is among the deadliest cancer types globally. In terms of cancer-related mortality rates, liver cancer ranks among the top three, underscoring the severity of this disease. Insufficient analysis has been conducted to fully understand the potential value of the extracellular matrix (ECM) in immune infiltration and the prognostic stratification of LIHC, despite its recognised importance in the development of this disease. The scRNA-seq data of GSE149614 was used to conduct single-cell analysis on 10 LIHC samples. CellChat scores were calculated for seven cell populations in the descending cohort to investigate cellular communication, while PROGENy scores were calculated to determine tumour-associated pathway scores in different cell populations. The pathway analysis using GO and KEGG revealed the enrichment of ECM-associated genes in the pathway, highlighting the potential role of the ECM in LIHC development. By utilizing the TCGA-LIHC cohort, an ECM-based prognostic model for LIHC was developed using Lasso regression. Immune infiltration scores were calculated using two methods, and the performance of the ECM-related risk score was evaluated using an independent cohort from the CheckMate study. To determine the precise expression of ECM-associated risk genes in LIHC, we evaluated hepatocellular carcinoma cell lines using a range of assays, including Western blotting, invasion assays and Transwell assays. Using single-cell transcriptome analysis, we annotated the spatially-specific distribution of major immune cell types in single-cell samples of LIHC. The main cell types identified and annotated included hepatocytes, T cells, myeloid cells, epithelial cells, fibroblasts, endothelial cells and B cells. The utilisation of cellchat and PROGENy analyses enabled the investigation and unveiling of signalling interactions, protein functionalities and the prominent influential pathways facilitated by the primary immune cell types within the LIHC. Numerous tumour pathways, including PI2K, EGFR and TGFb, demonstrated a close correlation with the involvement of ECM in LIHC. Moreover, an evaluation was conducted to assess the primary ECM-related functional changes and biological pathway enrichment in LIHC. Differential genes associated with ECM were identified and utilised to create prognostic models. The prognostic stratification value of these models for LIHC patients was confirmed through validation in multiple databases. Furthermore, through immune infiltration analysis, it was discovered that ECM might be linked to the irregular expression and regulation of numerous immune cells. Additionally, histone acetylation was mapped against gene mutation frequencies and differential expression profiles. The prognostic stratification efficacy of the ECM prediction model constructed in the context of PD-1 inhibitor therapy was also examined, and it exhibited strong stratification performance. Cellular experiments, including Western blotting, invasion and Transwell assays, revealed that ECM-associated risk genes have a promoting effect on the development of LIHC. The creation of biomarkers for LIHC using ECM-related genes unveiled substantial correlations with immune microenvironmental infiltration and functional mutations in various tumour pathways. This enlightens us to the possibility that the influence of ECM on tumours may extend beyond simply promoting the fibrotic process and the stromal composition of tumours.

Comparative analysis of vestibular endolymphatic hydrops grading methods and hearing loss in Ménière's disease: a retrospective MRI study using 3D-real inversion recovery sequence.

PURPOSE: To compare the correlation between different grading methods of vestibular endolymphatic hydrops (EH) and the severity of hearing loss in Ménière's disease (MD), and evaluate the diagnostic value of these methods in diagnosing MD. METHODS: This retrospective study included 30 patients diagnosed with MD from June 2021 to August 2023. All patients underwent inner ear MR gadolinium-enhanced imaging using three-dimensional (3D)-real inversion recovery sequences and pure-tone audiometry. The EH levels were independently evaluated according to the classification methods outlined by Nakashima et al. (Acta Otolaryngol Suppl 5-8, 2009. https://doi.org/10.1080/00016480902729827 ) (M1), Fang et al. (J Laryngol Otol 126:454-459, 2012. https://doi.org/10.1017/S0022215112000060 ) (M2), Barath et al. (Am J Neuroradiol 35:1387-1392, 2014. https://doi.org/10.3174/ajnr.A3856 ), (M3), Liu et al. (Front Surg 9:874971, 2022. https://doi.org/10.3389/fsurg.2022.874971 ), (M4), and Bernaerts et al. (Neuroradiology 61:421-429, 2019. https://doi.org/10.1007/s00234-019-02155-7 ) (M5), with a subsequent comparison of interobserver agreement. After achieving a consensus, an analysis was performed to explore the correlations between vestibular EH grading using different methods, the average hearing thresholds at low-mid, high-, and full frequencies and clinical stages. The diagnostic capabilities of these methods for MD were then compared. RESULTS: The interobserver consistency of M2-M5 was superior to that of M1. The EH grading based on M4 showed a significant correlation with the average hearing thresholds at low-mid, high-, and full frequencies and clinical stages. M1, M2, M3, and M5 correlated with some parameters. A receiver operating characteristic curve analysis indicated that M5 significantly outperformed M1, M2, M3, and M4 in terms of diagnostic efficiency for MD. CONCLUSION: M4 showed the strongest correlation with the degree of hearing loss in patients with MD, whereas M5 showed the highest diagnostic performance.

Chronic rhinosinusitis possibly associated with decreased lung function in chronic cough patients.

OBJECTIVES: The purpose of this study is to investigate the lung function in Chronic Rhinosinusitis (CRS) patients with Chronic Cough (CC). METHODS: A total of 1413 CC patients were retrospectively screened and 109 CRS patients with CC were enrolled. Lung function, Lund-Mackay Computed Tomography (CT) score, smoking status, peripheral blood eosinophil count, and immunoglobulin E concentration in serum samples, and Sino-Nasal Outcome Test were examined. Normal control subjects are also recruited. RESULTS: The Forced Expiratory Volume in 1 second (FEV1.0), Percent Predicted FEV1.0, and FEV1.0/Forced Vital Capacity (FVC) ratio in the patients were significantly low as compared with the control subjects. The FEV1.0/FVC ratio was negatively correlated with the Lund-Mackay CT scores of the patients with a high CT score. CONCLUSIONS: The CRS patients with CC should be investigated with lung function. In addition, the multidisciplinary evaluation including a pulmonologist is needed to manage the CRS patients with CC. LEVEL OF EVIDENCE: Level 4.

Initial [18F]DCFPyL PET/CT in treatment-naïve prostate cancer: correlation with post-ADT PSA outcomes and recurrence.

PURPOSE: Positron emission tomography (PET) with prostate-specific membrane antigen (PSMA) targeting tracers has emerged as a valuable diagnostic tool for prostate cancer (PCa), androgen deprivation therapy (ADT) stands as the cornerstone treatment for advanced PCa, yet forecasting the response to hormonal therapy poses a significant clinical hurdle. METHODS: In a prospective cohort of 86 PCa patients undergoing short-term ADT, this study evaluated the prognostic potential of [18F]DCFPyL PET/CT scans. Comprehensive data encompassing clinical profiles, baseline prostate-specific antigen (PSA) levels, and imaging metrics were assessed. We developed predictive models for assessing decreases in PSA levels (PSA50 and PSA70) based on a combination of PET-related parameters and clinical factors. Kaplan-Meier survival analysis was utilized to ascertain the prognostic value of PET-based metrics. RESULTS: In this study, elevated [18F]DCFPyL uptake within the primary tumor, as indicated by a SUV ≥ 6.78 (p = 0.0024), and a reduction in the tumor volume (TV) of primary PSMA-avid tumor with PSMA-TV < 41.96 cm3 (p = 0.038), as well as an increased burden of metastatic PSMA-avid tumor, with PSMA-TV (PSMA-TV ≥ 71.39 cm3) (p = 0.012) were identified in association with diminished progression-free survival (PFS). PET and clinical parameters demonstrated constrained predictive capacity for PSA50 response as indicated by an area under the curve (AUC) of 0.442. CONCLUSION: Our study revealed that pretreatment [18F]DCFPyL uptake in primary or metastatic tumor sites is prognostically relevant in high-risk PCa patients undergoing ADT. Further research is needed to develop robust predictive models in this multifaceted landscape of PCa management.

Intra-sample reversed pairs based on differentially ranked genes reveal biosignature for ovarian cancer.

Ovarian cancer, a major gynecological malignancy, often remains undetected until advanced stages, necessitating more effective early screening methods. Existing biomarker based on differential genes often suffers from variations in clinical practice. To overcome the limitations of absolute gene expression values including batch effects and biological heterogeneity, we introduced a pairwise biosignature leveraging intra-sample differentially ranked genes (DRGs) and machine learning for ovarian cancer detection across diverse cohorts. We analyzed ten cohorts comprising 872 samples with 796 ovarian cancer and 76 normal. Our method, DRGpair, involves three stages: intra-sample ranking differential analysis, reversed gene pair analysis, and iterative LASSO regression. We identified four DRG pairs, demonstrating superior diagnostic performance compared to current state-of-the-art biomarkers and differentially expressed genes in seven independent cohorts. This rank-based approach not only reduced computational complexity but also enhanced the specificity and effectiveness of biomarkers, revealing DRGs as promising candidates for ovarian cancer detection and offering a scalable model adaptable to varying cohort characteristics.

Biomimetic nano-chelate diethyldithiocarbamate Cu/Fe for enhanced metalloimmunity and ferroptosis activation in glioma therapy.

Ferroptosis has emerged as a promising therapeutic approach for glioma. However, its efficacy is often compromised by the activated GPX4-reduced glutathione (GSH) system and the poor brain delivery efficiency of ferroptosis inducers. Therefore, suppression of the GPX4-GSH axis to induce the accumulation of lipid peroxides becomes an essential strategy to augment ferroptosis. In this study, we present a metalloimmunological strategy to target the GPX4-GSH axis by inhibiting the cystine/glutamate antiporter system (system Xc-) and glutathione synthesis. To achieve this, we developed a complex of diethyldithiocarbamate (DDC) chelated with copper and ferrous ions (DDC/Cu-Fe) to trigger T-cell immune responses in the tumor microenvironment, as well as to inhibit tumor-associated macrophages, thereby alleviating immunosuppression. To enhance brain delivery, the DDC/Cu-Fe complex was encapsulated into a hybrid albumin and lactoferrin nanoparticle (Alb/LF NP), targeting the nutrient transporters (e.g., LRP-1 and SPARC) overexpressed in the blood-brain barrier (BBB) and glioma cells. The Alb/LF NP effectively promoted the brain accumulation of DDC/Cu-Fe, synergistically induced ferroptosis in glioma cells and activated anticancer immunity, thereby prolonging the survival of glioma-bearing mice. The nanoformulation of DDC/Cu-Fe provides a promising strategy that combines ferroptosis and metalloimmunology for glioma treatment.

Magnesium Depletion Score and Metabolic Syndrome in US Adults: Analysis of NHANES 2003-2018.

BACKGROUND: The association between magnesium status and metabolic syndrome remains unclear. This study aimed to examine the relationship between the kidney reabsorption-related magnesium depletion score (MDS) and metabolic syndrome among US adults. METHODS: We analyzed data from 15,565 adults participating in the National Health and Nutrition Examination Survey (NHANES) 2003-2018. Metabolic syndrome was defined according to the National Cholesterol Education Program's Adult Treatment Panel III report. The MDS is a scoring system developed to predict the status of magnesium deficiency that fully considers the pathophysiological factors influencing the kidneys' reabsorption capability. Weighted univariate and multivariate logistic regression were used to assess the association between MDS and metabolic syndrome. Restricted cubic spline analysis was conducted to characterize dose-response relationships. Stratified analyses by sociodemographic and lifestyle factors were also performed. RESULTS: In both univariate and multivariate analyses, higher MDS was significantly associated with increased odds of metabolic syndrome. Each unit increase in MDS was associated with approximately a 30% higher risk for metabolic syndrome, even after adjusting for confounding factors (OR 1.31; 95% CI 1.17-1.45). Restricted cubic spline graphs depicted a linear dose-response relationship across the MDS range. This positive correlation remained consistent across various population subgroups and exhibited no significant interaction by age, gender, race, adiposity, smoking status, or alcohol consumption. CONCLUSIONS: Higher urinary magnesium loss as quantified by MDS may be an independent linear risk factor for metabolic syndrome in US adults, irrespective of sociodemographic and behavioral factors. Optimizing magnesium nutritional status could potentially confer benefits to patients with metabolic syndrome.

Transfer-Printing of Insoluble Conducting Polymer for Soft 3D Conformal All-Organic Transistors.

The development of high-precision insoluble conducting polymer patterns for soft electronics is extremely challenging, mainly because of the incompatibility of the synthesis process with the underlying layers. In this study, a novel transfer-printing method is designed that enables the fabrication of photolithographic insoluble conducting polypyrrole (PPy) electrode patterns on soft substrates with high precision, demonstrating compatibility with various soft organic functional layers. Excellent mechanical stability, good biocompatibility, ultra-smooth surface, and outstanding conformability are observed. The photolithographic PPy electrode patterns, combined with an elastic organic semiconductor and dielectric, produce conformal all-organic transistors with mobility of 1.8 cm2 V-1 s-1. This study paves the way to use insoluble conducting polymers to develop complex, high-density flexible patterns and offers a promising organic electrode for the new-generation soft all-organic electronics.

Fluid-structure interaction study on the causes of mending material damage after sigmoid sinus wall reconstruction.

BACKGROUND AND OBJECTIVE: Sigmoid Sinus (SS) Wall Reconstruction (SSWR) is the mainstream treatment for pulsatile tinnitus (PT), but it has a high risk of recurrence. The damage of mending material is the key cause of recurrence, and its hemodynamic mechanism is still unclear. The purpose of this study was to investigate the hemodynamic causes of mending material breakage. METHODS: In this study, six patient-specific geometric models were reconstructed based on the data of the computed tomography angiography (CTA). The transient fluid-structure coupling method was performed to clarify the hemodynamic state of sigmoid sinus and the biomechanical state of the mending material. The distribution of stress and displacement and the flow pattern were calculated to evaluate the hemodynamic and biomechanics difference at the mending material area. RESULTS: The area of blood flow impact in some patients (2/6) was consistent with the damaged location of the mending material. The average stress (6/6) and average displacement (6/6) of damaged mending material were higher than those of complete mending material. All (6/6) patients showed that the high-stress and high-displacement proportion of the DMM region was higher than that of the CMM region. Moreover, the average stress fluctuation (6/6) and average displacement (6/6) fluctuation degree of damaged mending material is larger than that of complete mending material. CONCLUSIONS: The impact of blood and the uneven stress and displacement fluctuation of the mending material may be the causes of mending material damage. High stress and high displacement might be the key causes of the mending material damage.

Hemodynamic assessments of unilateral pulsatile tinnitus with jugular bulb wall dehiscence using 4D flow magnetic resonance imaging.

Background: Pulsatile tinnitus (PT) is a type of tinnitus characterized by a rhythmic sound that is synchronous with the heartbeat. One of the possible causes of PT is the jugular bulb wall dehiscence (JBWD). However, the hemodynamics of this condition are not well understood. To elucidate this issue, the present study aimed to compare the blood flow of PT patients with JBWD, PT patients with sigmoid sinus wall dehiscence (SSWD), and volunteers. Methods: A retrospective case-control study was conducted, which enrolled patients with unilateral PT who had undergone both computed tomography angiography (CTA) and four-dimensional (4D) flow magnetic resonance imaging (MRI) examinations at the Department of Otolaryngology-Head and Neck Surgery of Beijing Friendship Hospital affiliated to Capital Medical University between January 2019 and July 2023. After excluding the possible causes of PT, the patients were divided into the JBWD group and SSWD group according to the presence or absence of JBWD and/or SSWD. Finally, 11 female unilateral PT patients with JBWD (JBWD group, 11sides), 22 age- and side-matched female patients with SSWD (SSWD group, 22 sides), and 22 age-matched female volunteers (volunteer group, 36 sides) were enrolled. The area, maximum voxel velocity (Vv-max), maximum velocity (Vmax), average velocity (Vavg), and average blood flow rate (Q) were measured in the transverse sinuses (TSs), sigmoid sinuses (SSs), and jugular bulb (JB). The vortex flow pattern was also assessed. Fisher's exact test and Bonferroni correction were used for count data, with P<0.017 was considered statistically significant. Shapiro-Wilk test, one-way analysis of variance (ANOVA), Kruskal-Wallis H test, paired-samples t-test, and Wilcoxon matched-pairs signed-rank test were used for continuous variables depending on the distribution and variance of the data. The P<0.05 and corrected P<0.05 was considered statistically significant. Results: The area and Q of TSs and JB on the symptomatic side were higher than those on the contralateral side in the JBWD group (TSs: Parea=0.004, Pflow=0.002; JB: Parea=0.034, Pflow=0.018). The area was larger and velocities were lower in the JBWD group at the TSs than the SSWD group (Parea=0.004, PVv-max=0.009, PVmax=0.021, PVavg=0.026), and velocities were higher at the distal TSs and SSs than the volunteer group (TSs: PVv-max=0.042, PVmax=0.046, PVavg=0.040; SSs: PVv-max=0.007, PVmax=0.001, PVavg=0.001). At the JB, the JBWD group also had higher Vv-max than the volunteer group (P=0.012). The occurrence rate of vortex at JB in the JBWD group was higher than both the JBWD and the volunteer groups (P=0.002<0.017 and P=0.009<0.017, respectively). Conclusions: The blood flow of the intracranial venous sinus was different between the JBWD group and the SSWD group. The indicators that can differentiate include Vv-max, Vmax, Vavg, vortex, and TSs cross-sectional area.