Unveiling the next generation of MRI contrast agents: current insights and perspectives on ferumoxytol-enhanced MRI.

Contrast-enhanced magnetic resonance imaging (CE-MRI) is a pivotal tool for global disease diagnosis and management. Since its clinical availability in 2009, the off-label use of ferumoxytol for ferumoxytol-enhanced MRI (FE-MRI) has significantly reshaped CE-MRI practices. Unlike MRI that is enhanced by gadolinium-based contrast agents, FE-MRI offers advantages such as reduced contrast agent dosage, extended imaging windows, no nephrotoxicity, higher MRI time efficiency and the capability for molecular imaging. As a leading superparamagnetic iron oxide contrast agent, ferumoxytol is heralded as the next generation of contrast agents. This review delineates the pivotal clinical applications and inherent technical superiority of FE-MRI, providing an avant-garde medical-engineering interdisciplinary lens, thus bridging the gap between clinical demands and engineering innovations. Concurrently, we spotlight the emerging imaging themes and new technical breakthroughs. Lastly, we share our own insights on the potential trajectory of FE-MRI, shedding light on its future within the medical imaging realm.

Association between periprocedural myocardial injury and neointimal characteristics in patients with in-stent restenosis: an optical coherence tomography study.

Background: The relationship between neointimal characteristics of in-stent restenosis (ISR) and periprocedural myocardial injury (PMI) remains unclear. Therefore, this study aimed to investigate the relationship between PMI and neointimal characteristics of ISR by using optical coherence tomography (OCT). Methods: This was a retrospective study. We enrolled 140 patients diagnosed with ISR with normal baseline high-sensitivity troponin T (hs-cTnT) levels who underwent OCT and subsequent revascularization by means of drug-coated balloon (DCB) or drug-eluting stent (DES) between October 2018 and October 2022 in the Affiliated Hospital of Zunyi Medical University. Based on the 4th universal definition of myocardial infarction, patients whose hs-cTnT were increased five times above the upper reference limit (URL) after percutaneous coronary interventions (PCI) were deemed to PMI. The patients were subdivided into PMI (n=53) and non-PMI (n=87) groups. In the univariable analysis, variables in the baselines, angiography characteristics and OCT findings were analyzed with binary logistic regression. A P value of <0.2 was included in the multivariable model. Multivariable logistic regression analysis was used to identify the independent predictors of PMI. Results: The prevalence of intra-intimal microvessels in patients with PMI was higher than in those without PMI (58.5% vs. 32.2%, P=0.003). The ratio of intra-stent plaque rupture (PR) was also higher in patients with PMI (60.4% vs. 40.2%, P=0.021). Multivariable logistic regression analysis showed that intra-intimal microvessels [odds ratio (OR): 3.193, 95% confidence interval (CI): 1.280-7.966; P=0.013] and intra-stent PR (OR: 2.124, 95% CI: 1.153-4.732; P=0.035) were independently associated with PMI. Conclusions: Intra-intimal microvessels and intra-stent PR were independently associated with PMI. Accurate identification and recognition of intra-intimal microvessels and intra-stent PR may be helpful in preventing PMI.

Barriers and Facilitators of Medication Adherence in Hypertension Patients: A Meta-Integration of Qualitative Research.

The aim of this qualitative systematic review is to analyze the barriers and facilitators to the uptake of antihypertensive medication in hypertensive patients. The databases of PubMed, Embase, Web of Science, CINAHL, Cochrane Library, MEDLINE, China National Knowledge Infrastructure, Wanfang, VIP, and Chinese Biomedical were searched from inception to June 2023. The studies were screened, extracted, and assessed independently by two researchers. Previously, the researchers used the Joanna Briggs Institute Critical Appraisal Checklist for Qualitative Research to assess the quality of the included studies. A total of 27 studies were considered, resulting in two combined findings: a good level of knowledge, belief, and behavior and adequate social support were facilitators of medication adherence in hypertensive patients. In contrast, lack of medication literacy, difficulty adapting to roles, reduced sense of benefit from treatment, limited access to healthcare resources, and unintentional nonadherence were barriers. Medication adherence in hypertensive patients remains a challenge to be addressed. Future research should explore how complex interventions using a combination of evidence-based strategies and targeting multiple adherence behaviors (eg, long-term adherence to medication) are effective in improving medication adherence.

Biodegradable ferroelectric molecular crystal with large piezoelectric response.

Transient implantable piezoelectric materials are desirable for biosensing, drug delivery, tissue regeneration, and antimicrobial and tumor therapy. For use in the human body, they must show flexibility, biocompatibility, and biodegradability. These requirements are challenging for conventional inorganic piezoelectric oxides and piezoelectric polymers. We discovered high piezoelectricity in a molecular crystal HOCH2(CF2)3CH2OH [2,2,3,3,4,4-hexafluoropentane-1,5-diol (HFPD)] with a large piezoelectric coefficient d33 of ~138 picocoulombs per newton and piezoelectric voltage constant g33 of ~2450 × 10-3 volt-meters per newton under no poling conditions, which also exhibits good biocompatibility toward biological cells and desirable biodegradation and biosafety in physiological environments. HFPD can be composite with polyvinyl alcohol to form flexible piezoelectric films with a d33 of 34.3 picocoulombs per newton. Our material demonstrates the ability for molecular crystals to have attractive piezoelectric properties and should be of interest for applications in transient implantable electromechanical devices.

A multiscale modeling study of nanoparticle-based targeting therapy against atherosclerosis.

Although researches on nanoparticle-based (NP-based) drug delivery system for atherosclerosis treatment have grown rapidly in recent years, there are limited studies in quantifying the effects of targeting drugs on plaque components and microenvironment. The purpose of the present study was to quantitatively assess the targeting therapeutic effects against atherosclerosis by establishing a multiscale mathematical model. The multiscale model involved subcellular, cellular and microenvironmental scales to simulate lipid catabolism, macrophage behaviors and dynamics of microenvironmental components, respectively. In vitro and in vivo experimental data were integrated into the mathematical model according to Bayesian statistics, in order to evaluate the therapeutic effects of a proposed NP-based platform for macrophage-specific delivery to simultaneously deliver SR-A siRNA (to reduce LDL uptake) and LXR-L (to stimulate cholesterol efflux). Dosage variation analysis was then performed to investigate the drug efficacy under varied dosage combinations of SR-A siRNA and LXR-L. The simulation results demonstrated that the dynamics of the microenvironmental components presented different developments in Untreated and Treated groups. We also found that the balance of lipid metabolism between uptake and efflux resulted in the improvement of lipid and inflammatory microenvironment, consequently in the plaque regression. In addition, the model predicted optimized dosage combinations according to the co-effect analysis of the two drugs on the lipid microenvironment. This study suggests that multiscale modeling can be a powerful quantitative tool for estimating the therapeutic effects of targeting drugs for plaque regression and designing the enhanced treatment strategies against atherosclerosis.

Birth weight discordance and adverse neonatal outcomes in appropriately grown premature twins.

Objective: This study aimed to analyze the clinical characteristics of birth weight discordant twins (BWDT) who were premature and appropriate-for-gestational-age or large-for-gestational-age. Additionally, it assessed the impact of birth weight discordance on the prognosis of appropriately grown premature twins, and investigated the effect of maternal factors on neonatal outcomes. Study design: This retrospective cohort study included twins who were born alive after preterm labor at the Nanjing Drum Tower Hospital from January 2018 to December 2021, along with their mothers. Twins were arranged into discordant and concordant groups according to intertwin birth weight discordance, followed by the analysis of the clinical characteristics of mothers and the prognosis of neonates. Results: A total of 585 mothers and 1170 neonates were included, with 47 mothers and 94 neonates in the discordant group. The incidence of birth weight discordance was 8.0% (94/1,170) in appropriately grown premature twins. The incidence of complications (43.2% vs. 21.8%) and transfer to the neonatal intensive care unit (NICU) (53.2% vs. 29.2%) was higher in the discordant group than in the concordant group (p < 0.05). Furthermore, the incidence of infectious diseases (36.7% vs. 19.4%), necrotizing enterocolitis (7.6% vs. 1.6%), and oxygen therapy rate (22.8% vs. 12.8%) were statistically significantly higher in the discordant group than in the concordant group (p < 0.05). Conclusion: Birth weight discordance remains a high-risk factor for complications and transfer to the NICU in appropriately grown premature twins. It is important to pay attention to birth weight discordance when the outcomes of twins are assessed.

Foodborne Carbon Dots Aggravate High-Fat-Diet-Induced Glucose Homeostasis Imbalance by Disrupting the Gut-Liver Axis.

Foodborne carbon dots (CDs) are generally produced during cooking and exist in food items. Generally, CDs are regarded as nontoxic materials, but several studies have gradually confirmed the cytotoxicity of CDs, such as oxidative stress, reduced cellular activity, apoptosis, etc. However, studies focusing on the health effects of long-term intake of food-borne CDs are scarce, especially in populations susceptible to metabolic disease. In this study, we reported that CDs in self-brewing beer had no effect on glucose metabolism in CHOW-fed mice but exacerbated high-fat-diet (HFD)-induced glucose metabolism disorders via the gut-liver axis. Chronic exposure to foodborne CDs increased fasting glucose levels and exacerbated liver and intestinal barrier damage in HFD-fed mice. The 16s rRNA sequencing analysis revealed that CDs significantly altered the gut microbiota composition and promoted lipopolysaccharide (LPS) synthesis-related KEGG pathways (superpathway of (Kdo)2-lipid A, Kdo transfer to lipid IVA Ill (Chlamydia), lipid IVA biosynthesis, and so on) in HFD-fed mice. Mechanically, CD exposure increased the abundance of Gram-negative bacteria (Proteobacteria and Desulfovibrionaceae), thus producing excessive endotoxin-LPS, and then LPS was transferred by the blood circulation to the liver due to the damaged intestinal barrier. In the liver, LPS promoted TLR4/NF-κB/P38 MAPK signaling, thus enhancing systemic inflammation and exacerbating HFD-induced insulin resistance. However, pretreating mice with antibiotics eliminated these effects, indicating a key role for gut microbiota in CDs exacerbating glucose metabolism disorders in HFD-fed mice. The finding herein provides new insight into the potential health risk of foodborne nanoparticles in susceptible populations by disturbing the gut-liver axis.

Iron Oxide Nanoparticles Engineered Macrophage-Derived Exosomes for Targeted Pathological Angiogenesis Therapy.

Engineering exosomes with nanomaterials usually leads to the damage of exosomal membrane and bioactive molecules. Here, pathological angiogenesis targeting exosomes with magnetic imaging, ferroptosis inducing, and immunotherapeutic properties is fabricated using a simple coincubation method with macrophages being the bioreactor. Extremely small iron oxide nanoparticle (ESIONPs) incorporated exosomes (ESIONPs@EXO) are acquired by sorting the secreted exosomes from M1-polarized macrophages induced by ESIONPs. ESIONPs@EXO suppress pathological angiogenesis in vitro and in vivo without toxicity. Furthermore, ESIONPs@EXO target pathological angiogenesis and exhibit an excellent T1-weighted contrast property for magnetic resonance imaging. Mechanistically, ESIONPs@EXO induce ferroptosis and exhibit immunotherapeutic ability toward pathological angiogenesis. These findings demonstrate that a pure biological method engineered ESIONPs@EXO using macrophages shows potential for targeted pathological angiogenesis therapy.

Thyroid ultrasound diagnosis improvement via multi-view self-supervised learning and two-stage pre-training.

Thyroid nodule classification and segmentation in ultrasound images are crucial for computer-aided diagnosis; however, they face limitations owing to insufficient labeled data. In this study, we proposed a multi-view contrastive self-supervised method to improve thyroid nodule classification and segmentation performance with limited manual labels. Our method aligns the transverse and longitudinal views of the same nodule, thereby enabling the model to focus more on the nodule area. We designed an adaptive loss function that eliminates the limitations of the paired data. Additionally, we adopted a two-stage pre-training to exploit the pre-training on ImageNet and thyroid ultrasound images. Extensive experiments were conducted on a large-scale dataset collected from multiple centers. The results showed that the proposed method significantly improves nodule classification and segmentation performance with limited manual labels and outperforms state-of-the-art self-supervised methods. The two-stage pre-training also significantly exceeded ImageNet pre-training.

Magnetic Characterization of Human Intrinsically Magnetic Monocytes Through a Novel Optical Tracking-Based Magnetic Sensor.

Intrinsically magnetic cells naturally occur within organisms and are believed to be linked to iron metabolism and certain cellular functions while the functional significance of this magnetism is largely unexplored. To better understand this property, an approach named Optical Tracking-based Magnetic Sensor (OTMS) has been developed. This multi-target tracking system is designed to measure the magnetic moment of individual cells. The OTMS generates a tunable magnetic field and induces movement in magnetic cells that are subsequently analyzed through a learning-based tracking-by-detection system. The magnetic moment of numerous cells can be calculated simultaneously, thereby providing a quantitative tool to assess cellular magnetic properties within populations. Upon deploying the OTMS, a stable population of magnetic cells in human peripheral monocytes is discovered. Further application in the analysis of clinical blood samples reveals an intriguing pattern: the proportion of magnetic monocytes differs significantly between systemic lupus erythematosus (SLE) patients and healthy volunteers. This variation is positively correlated with disease activity, a trend not observed in patients with rheumatoid arthritis (RA). The study, therefore, presents a new frontier in the investigation of the magnetic characteristics of naturally occurring magnetic cells, opening the door to potential diagnostic and therapeutic applications that leverage cellular magnetism.

Impacts of national volume-based drug procurement policy on the utilization and costs of antihypertensive drugs in a Chinese medicine hospital: an interrupted time series analysis of 5138 patients.

Objectives: The study aimed to estimate the effects of National Volume-based Drug Procurement (NVBP) policy on drug utilization and medical expenditures of hypertension patients in public medical institutions in mainland China. Methods: This study used patient-level data based on electronic health records retrieved from the hospital information system of Nanjing Hospital of Chinese Medicine. Data on patients with hypertension who received care at this institution between 2016 and 2021 was used for analysis. Segmented linear regression models incorporating Interrupted Time Series (ITS) analysis were adopted to examine the effects of NVBP policy on drug utilization and health expenditures of eligible patients. Drug utilization volume and health expenditures were the primary outcomes used to assess the policy effects, and were measured using the prescription proportion of each drug class and the overall per-encounter treatment costs. Results: After the implementation of NVBP policy, the volume of non-winning drugs decreased from 54.42% to 36.25% for outpatient care and from 35.62% to 15.65% for inpatient care. The ITS analysis showed that the volume of bid-winning drugs in outpatient and inpatient settings increased by 9.55% (p < 0.001) and 6.31% (p < 0.001), respectively. The volume changes in non-volume based purchased (non-VBP) drugs differed between outpatients and inpatients. The proportion of non-VBP drugs immediately increased by 5.34% (p = 0.002) overall, and showed an upward trend in the outpatient setting specially (p < 0.001) during the post-intervention period. However, no significant differences were observed in the proportion of non-VBP drugs in inpatient setting (p > 0.05) in term of level change (p > 0.05) or trend change (p > 0.05). The average per-visit expenditures of outpatients across all drug groups exhibited an upward trend (p < 0.05) post policy intervention. In addition, a similar increase in the overall costs for chemical drugs were observed in inpatient settings (coefficient = 2,599.54, p = 0.036), with no statistically significant differences in the regression slope and level (p = 0.814). Conclusion: The usage proportion of bid-winning drugs increased significantly post policy intervention, indicating greater use of bid-winning drugs and the corresponding substitution of non-winning hypertensive drugs. Drug expenditures for outpatients and health expenditures per visit for inpatients also exhibited an upward trend, suggesting the importance of enhanced drug use management in Traditional Chinese Medicine hospital settings.

Advances in Atherosclerosis Theranostics Harnessing Iron Oxide-Based Nanoparticles.

Atherosclerosis, a multifaceted chronic inflammatory disease, has a profound impact on cardiovascular health. However, the critical limitations of atherosclerosis management include the delayed detection of advanced stages, the intricate assessment of plaque stability, and the absence of efficacious therapeutic strategies. Nanotheranostic based on nanotechnology offers a novel paradigm for addressing these challenges by amalgamating advanced imaging capabilities with targeted therapeutic interventions. Meanwhile, iron oxide nanoparticles have emerged as compelling candidates for theranostic applications in atherosclerosis due to their magnetic resonance imaging capability and biosafety. This review delineates the current state and prospects of iron oxide nanoparticle-based nanotheranostics in the realm of atherosclerosis, including pivotal aspects of atherosclerosis development, the pertinent targeting strategies involved in disease pathogenesis, and the diagnostic and therapeutic roles of iron oxide nanoparticles. Furthermore, this review provides a comprehensive overview of theranostic nanomedicine approaches employing iron oxide nanoparticles, encompassing chemical therapy, physical stimulation therapy, and biological therapy. Finally, this review proposes and discusses the challenges and prospects associated with translating these innovative strategies into clinically viable anti-atherosclerosis interventions. In conclusion, this review offers new insights into the future of atherosclerosis theranostic, showcasing the remarkable potential of iron oxide-based nanoparticles as versatile tools in the battle against atherosclerosis.

Morphological characteristics of in-stent restenosis with different degrees of area stenosis: an optical coherence tomography study.

The morphological characteristics of in-stent restenosis (ISR) in relation to varying degrees of area stenosis have not been comprehensively examined. This study aimed to explore the tissue characteristics of patients experiencing ISR with different degrees of area stenosis through the utilization of optical coherence tomography (OCT). In total, 230 patients with ISR who underwent OCT were divided into the following three groups: area stenosis (AS) < 70% (n = 26); 70-80% (n = 119) and AS ≥ 80% (n = 85). Among the 230 patients, the clinical presentation as stable angina was 61.5% in AS < 70%, followed by 47.2% in 70% < AS ≤ 80%, and 31.8% in AS ≥ 80% (P = 0.010). The OCT findings showed that heterogeneous neointima, ISNA, LRP, neointima rupture, TCFA-like pattern, macrophage infiltration, red and white thrombus was more common with AS increased. Ordinal logistic regression analysis showed that higher AS was associated with previous dyslipidemia (odds ratio [OR], 4.754; 95% confidence interval [CI], 1.419-15.927, P = 0.011), neointimal rupture (OR: 3.640; 95% CI, 1.169-11.325, P = 0.026), red thrombus (OR: 4.482; 95% CI, 1.269-15.816, P = 0.020) and white thrombus (OR: 5.259; 95% CI, 1.660-16.659, P = 0.005). Patients with higher degrees of area stenosis in the context of ISR exhibited a greater number of discernible morphological characteristics as identified through OCT analysis. Furthermore, previous dyslipidemia, neointimal rupture, white thrombus and red thrombus were highly associated with and the progression of ISR lesions.

Efficacy of an enhanced recovery nursing plan as a rooming-in practice for women with preeclampsia post-cesarean section.

Our purpose was to develop and evaluate the clinical outcomes of a nursing plan as a rooming-in practice for enhanced recovery of women with preeclampsia following a cesarean section. The authors developed a postoperative enhanced recovery nursing plan as a rooming-in practice for women with preeclampsia based on summarizing evidence-based best practices. The authors used convenience sampling to select women with preeclampsia after a cesarean section from the obstetrics department of a Class A tertiary hospital in Nanjing, China, as the participants in our study. There were 30 women in the experimental group. The postoperative enhanced recovery nursing care plan was formulated for five postoperative time points and incorporated management of blood pressure, temperature, and fluids, as well as monitoring of complications, pain management, activity and rest, diet management, and breastfeeding. The control group consisted of 30 women who received routine nursing care and health education. The authors compared levels of maternal self-efficacy, breastfeeding efficacy, anxiety, pain scores, and deep vein thrombosis (DVT) prevention compliance before and after the intervention. Women in the experimental group had a self-efficacy score of 7.5 ± 0.63, which was higher than that in the control group (5.4 ± 0.85); they had a higher breastfeeding efficacy score of 7.13 ± 0.68 when compared to the control group (4.23 ± 0.86); the anxiety score was 6.7 ± 1.62, which was lower than that in the control group (10.03 ± 1.87); and the pain score was lower at 3.26 ± 0.52 when compared to the control group (3.83 ± 0.83). All the differences were statistically significant (P < 0.05). Postoperative blood pressure was controlled within the target range, and the rate of DVT prevention compliance increased in the experimental group. The implementation of a postoperative enhanced recovery nursing intervention for women with preeclampsia as part of the rooming-in practice was effective in helping manage the blood pressure, pain, and fluids of women with preeclampsia, improved their postoperative self-management ability and breastfeeding efficacy, reduced their anxiety levels, improved their compliance with the prevention of related complications, and ultimately promoted enhanced postoperative recovery, thereby guaranteeing the safety of mothers and newborns.

Elucidating the Bioinspired Synthesis Process of Magnetosomes-Like Fe3 O4 Nanoparticles.

Iron oxide nanoparticles are a kind of important biomedical nanomaterials. Although their industrial-scale production can be realized by the conventional coprecipitation method, the controllability of their size and morphology remains a huge challenge. In this study, a kind of synthetic polypeptide Mms6-28 which mimics the magnetosome protein Mms6 is used for the bioinspired synthesis of Fe3 O4 nanoparticles (NPs). Magnetosomes-like Fe3 O4 NPs with uniform size, cubooctahedral shape, and smooth crystal surfaces are synthesized via a partial oxidation process. The Mms6-28 polypeptides play an important role by binding with iron ions and forming nucleation templates and are also preferably attached to the [100] and [111] crystal planes to induce the formation of uniform cubooctahedral Fe3 O4 NPs. The continuous release and oxidation of Fe2+ from pre-formed Fe2+ -rich precursors within the Mms6-28-based template make the reaction much controllable. The study affords new insights into the bioinspired- and bio-synthesis mechanism of magnetosomes.

A Self-Homing and Traceable Cardiac Patch Leveraging Ferumoxytol for Spatiotemporal Therapeutic Delivery.

Mesenchymal stem cell (MSC)-based cardiac patches are envisioned to be a promising treatment option for patients with myocardial infarction. However, their therapeutic efficacy and duration are hampered due to their limited retention on the epicardium. We engineered a scaffold-free MSC sheet with an inherent ability to migrate into the infarcted myocardium, a strategy enabled by actively establishing a sustained intracellular hypoxic environment through the endocytosis of our FDA-approved ferumoxytol. This iron oxide nanoparticle stabilized hypoxia-induced factor-1α, triggering upregulation of the CXC chemokine receptor and subsequent MSC chemotaxis. Thus, MSCs integrated into 2/3 depth of the left ventricular anterior wall in a rat model of acute myocardial infarction and persisted for at least 28 days. This led to spatiotemporal delivery of paracrine factors by MSCs, enhancing cardiac regeneration and function. Ferumoxytol also facilitated the noninvasive MRI tracking of implanted MSCs. Our approach introduces a strategy for mobilizing MSC migration, holding promise for rapid clinical translation in myocardial infarction treatment.

Association Between Serum Uric Acid Levels and Neoatherosclerosis.

Neoatherosclerosis is a major cause of stent failure after percutaneous coronary intervention. Metabolism such as hyperuricemia is associated with in-stent restenosis (ISR). However, the association between serum uric acid (sUA) levels and in-stent neoatherosclerosis (ISNA) has never been validated.A total of 216 patients with 220 ISR lesions who had undergone optical coherence tomography (OCT) of culprit stents were included in this study. According to their sUA levels, eligible patients were divided into two groups [normal-sUA group: sUA < 7 mg/dL, n = 126, and high-sUA group: sUA ≥ 7 mg/dL, n = 90]. OCT findings were analyzed and compared between the normal- and high-sUA groups.The incidence of ISNA (63.0% versus 43.0%, P = 0.004) was significantly higher in the high-sUA group than in the normal-sUA group. Lipid plaques (66.3% versus 43.0%, P < 0.001) and thin-cap fibroatheroma (38.0% versus 18.0%, P = 0.001) were observed more frequently in the restenotic tissue structure in patients in the high-sUA group than in those in the normal-sUA group. Meanwhile, univariate (OR: 1.208, 95% CI: 1.037-1.407; P = 0.015) and multivariate (OR: 1.254, 95% CI: 1.048-1.501; P = 0.013) logistic regression analyses indicated that sUA levels were an independent risk factor for ISNA after adjusting for relevant risk factors.The high-sUA levels were an independent risk factor for the occurrence of neoatherosclerosis in patients with ISR via OCT.

Methylparaben induces hepatic glycolipid metabolism disorder by activating the IRE1α-XBP1 signaling pathway in male mice.

Methylparaben (MP), a preservative widely used in daily supplies, exists in both the environment and the human body. However, the potential health risks posed by MP remain unclear. This study aimed to unravel the mechanisms by which MP disrupts glucose and lipid homeostasis. For this, we administered MP to mice and observed changes in glucose and lipid metabolism. MP exposure led to hyperglycemia, hyperlipidemia, visceral organ injury, and hepatic lipid accumulation. RNA sequencing results from mice livers indicated a close association between MP exposure and endoplasmic reticulum (ER) stress, inflammatory response, and glucose and lipid homeostasis. Western blotting and quantitative reverse transcription-polymerase chain reaction revealed that MP activated ER stress, particularly the inositol-requiring enzyme 1 (IRE1)/X-box binding protein 1 (XBP1) pathway, which further promoted the activation of the nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. The activation of these pathways phosphorylated insulin receptor substrate-1 (IRS1) (ser 307), resulting in decreased phosphorylation of protein kinase B (Akt) (ser 473), leading to insulin resistance. Additionally, MP exposure promoted lipogenesis through ER stress. To explore potential remedies, we administered the ER stress inhibitor 4-phenylbutyric acid (4-PBA) and the IRE1α-XBP1 pathway inhibitor toyocamycin to mice, both of which protected against metabolic disorders and organ injury caused by MP. These findings suggest that MP induces disruptions in glucose and lipid metabolism through ER stress, primarily through the IRE1α-XBP1 pathway.

PGS-Depot: a comprehensive resource for polygenic scores constructed by summary statistics based methods.

Polygenic score (PGS) is an important tool for the genetic prediction of complex traits. However, there are currently no resources providing comprehensive PGSs computed from published summary statistics, and it is difficult to implement and run different PGS methods due to the complexity of their pipelines and parameter settings. To address these issues, we introduce a new resource called PGS-Depot containing the most comprehensive set of publicly available disease-related GWAS summary statistics. PGS-Depot includes 5585 high quality summary statistics (1933 quantitative and 3652 binary trait statistics) curated from 1564 traits in European and East Asian populations. A standardized best-practice pipeline is used to implement 11 summary statistics-based PGS methods, each with different model assumptions and estimation procedures. The prediction performance of each method can be compared for both in- and cross-ancestry populations, and users can also submit their own summary statistics to obtain custom PGS with the available methods. Other features include searching for PGSs by trait name, publication, cohort information, population, or the MeSH ontology tree and searching for trait descriptions with the experimental factor ontology (EFO). All scores, SNP effect sizes and summary statistics can be downloaded via FTP. PGS-Depot is freely available at http://www.pgsdepot.net.

The Story of Ferumoxytol: Synthesis Production, Current Clinical Applications, and Therapeutic Potential.

Ferumoxytol, approved by the U.S. Food and Drug Administration in 2009, is one of the intravenous iron oxide nanoparticles authorized for the treatment of iron deficiency in chronic kidney disease and end-stage renal disease. With its exceptional magnetic properties, catalytic activity, and immune activity, as well as good biocompatibility and safety, ferumoxytol has gained significant recognition in various biomedical diagnoses and treatments. Unlike most existing reviews on this topic, this review primarily focuses on the recent clinical and preclinical advances of ferumoxytol in disease treatment, spanning anemia, cancer, infectious inflammatory diseases, regenerative medicine application, magnetic stimulation for neural modulation, etc. Additionally, the newly discovered mechanisms associated with the biological effects of ferumoxytol are discussed, including its magnetic, catalytic, and immunomodulatory properties. Finally, the summary and future prospects concerning the treatment and application of ferumoxytol-based nanotherapeutics are presented.