For decades, poly(ethylene glycol) (PEG) has been widely incorporated into nanoparticles for evading immune clearance and improving the systematic circulation time. However, recent studies have ...reported a phenomenon known as “accelerated blood clearance (ABC)” where a second dose of PEGylated nanomaterials is rapidly cleared when given several days after the first dose. Herein, we demonstrate that natural red blood cell (RBC) membrane is a superior alternative to PEG. Biomimetic RBC membrane‐coated Fe3O4 nanoparticles (Fe3O4@RBC NPs) rely on CD47, which is a “don't eat me” marker on the RBC surface, to escape immune clearance through interactions with the signal regulatory protein‐alpha (SIRP‐α) receptor. Fe3O4@RBC NPs exhibit extended circulation time and show little change between the first and second doses, with no ABC suffered. In addition, the administration of Fe3O4@RBC NPs does not elicit immune responses on neither the cellular level (myeloid‐derived suppressor cells (MDSCs)) nor the humoral level (immunoglobulin M and G (IgM and IgG)). Finally, the in vivo toxicity of these cell membrane‐camouflaged nanoparticles is systematically investigated by blood biochemistry, hematology testing, and histology analysis. These findings are significant advancements toward solving the long‐existing clinical challenges of developing biomaterials that are able to resist both immune response and rapid clearance.
Red blood cell membrane‐camouflaged Fe3O4 nanoparticles (Fe3O4@RBC NPs) exhibit prolonged circulation time in the blood with no adverse effects. There is little change between a first and second dose, and no accelerated blood clearance is seen, as is generally the case for PEGylated nanomaterials. This is a significant advancement toward developing biomaterials that are able to resist both immune response and rapid clearance.
Since the beginning of the COVID-19 pandemic, older Asians have experienced a rise in racism and discrimination based on their race and ethnicity. This study examines how anti-Asian hate impacts ...older Asians' mental, social, and physical health.
From March 18, 2022 to January 24, 2023, we conducted a cross-sectional survey study of community-dwelling Asian/Asian American adults aged ≥50 years from the San Francisco Bay Area. Measures included perceptions of anti-Asian hate; direct encounters with hate incidents; indirect experiences with hate incidents (e.g. knowing a friend who was a victim); reports of anxiety, depression, loneliness, and changes in daily activities; ways to address these issues; and discussions with clinicians about hate incidents.
Of the 293 older Asians, 158 (54%) were Vietnamese and 97 (33%) Chinese. Eighty-five (29%) participants were direct victims of anti-Asian hate, 112 (38%) reported anxiety, 105 (36%) reported depression, 161 (55%) reported loneliness, and 142 (48%) reported decreased daily activities. Compared with those who were "not-at-all" to "moderately" worried about hate incidents, participants who were "very" to "extremely" worried experienced heightened anxiety (42% versus 16%), loneliness (30% versus 14%), and changes in daily activities (66% versus 31%), p < 0.01 for all. Most participants (72%) felt comfortable discussing hate incidents with clinicians; however, only 31 (11%) reported that a clinician had talked with them about these incidents.
Both directly and indirectly, anti-Asian hate negatively impacts older Asians' mental, social, and physical health. Clinicians have a role in addressing the health impacts of anti-Asian hate.
Specialized functions of macrophages have evolved to protect the body from infection. However, the same mechanisms that enable phagocytosis of pathogens and activation of leukocytes also permit the ...uptake of lipoproteins and release of reactive oxygen species and immune mediators that collectively contribute to atherosclerosis. New approaches to inhibit lipid accumulation in macrophage foam cells and reduce inflammatory responses may be of therapeutic value in preventing coronary artery disease.
Prediction of endoscopic post-operative recurrence (POR) in Crohn’s disease (CD) patients following ileocolonic resection (ICR) using clinical risk factors alone has thus far been inadequate. While ...peripheral blood leukocyte (PBL) DNA methylation has shown promise as a tool for predicting recurrence in cancer, no data in CD patients exists. Therefore, this study explored the association and predictive value of PBL DNA methylation in CD patients following ICR. From a cohort of 117 CD patients undergoing ICR, epigenome-wide PBL methylation profiles from 25 carefully selected patients presenting either clear endoscopic remission (n = 12) or severe recurrence (n = 13) were assessed using the Illumina MethylationEPIC (850K) array. No statistically significant differentially methylated positions (DMPs) or regions (DMRs) associated with endoscopic POR were identified (FDR p ≤ 0.05), further evidenced by the low accuracy (0.625) following elastic net classification analysis. Nonetheless, interrogating the most significant differences in methylation suggested POR-associated hypermethylation in the MBNL1, RAB29 and LEPR genes, respectively, which are involved in intestinal fibrosis, inflammation and wound healing. Notably, we observed a higher estimated proportion of monocytes in endoscopic POR compared to remission. Altogether, we observed limited differences in the genome-wide DNA methylome among CD patients with and without endoscopic POR. We therefore conclude that PBL DNA methylation is not a feasible predictive tool in post-operative CD.
Purpose
This study aims to clarify the association between metastatic pattern and prognosis in stage IV gastric cancer, with a focus on patients presenting with metastases limited to nonregional ...lymph nodes.
Methods
In this retrospective cohort study, the National Cancer Database was used to identify patients ≥ 18 years of age diagnosed with stage IV gastric cancer between 2016 and 2019. Patients were stratified according to pattern of metastatic disease at diagnosis: nonregional lymph nodes only (“stage IV-nodal”), single systemic organ (“stage IV-single organ”), or multiple organs (“stage IV-multi-organ”). Survival was assessed by Kaplan-Meier curves and multivariable Cox models in unadjusted and propensity score-matched samples.
Results
Overall, 15,050 patients were identified, including 1,349 (8.7%) stage IV-nodal patients. Most patients in each group received chemotherapy 68.6% of stage IV-nodal patients, 65.2% of stage IV-single organ patients, and 63.5% of stage IV-multi-organ patients (
p
= 0.003). Stage IV-nodal patients exhibited better median survival (10.5 months, 95% CI 9.7–11.9,
p
< 0.001) than single organ (8.0, 95% CI 7.6–8.2) and multi-organ (5.7, 95% CI 5.4–6.0) patients. In the multivariable Cox model, stage IV-nodal patients also exhibited better survival (HR 0.79, 95% CI 0.73–0.85,
p
< 0.001) than single organ (reference) and multi-organ (HR 1.27, 95% CI 1.22–1.33,
p
< 0.001) patients.
Conclusions
Nearly 9% of clinical stage IV gastric cancer patients have their distant disease confined to nonregional lymph nodes. These patients were managed similarly to other stage IV patients but experienced a better prognosis, suggesting opportunities to introduce M1 staging subclassifications.
SignificanceThe free energy functional is a central component of continuum dynamical models used to describe phase transitions, microstructural evolution, and pattern formation. However, despite the ...success of these models in many areas of physics, chemistry, and biology, the standard free energy frameworks are frequently characterized by physically opaque parameters and incorporate assumptions that are difficult to assess. Here, we introduce a mathematical formalism that provides a unifying umbrella for constructing free energy functionals. We show that Ginzburg-Landau framework is a special case of this umbrella and derive a generalization of the widely employed Cahn-Hilliard equation. More broadly, we expect the framework will also be useful for generalizing higher-order theories, establishing formal connections to microscopic physics, and coarse graining.
The Lone Star tick, Amblyomma americanum is important to human health because of a variety of pathogenic organisms transmitted to humans during feeding events, which underscores the need to identify ...novel approaches to prevent tick bites. Thus, the goal of this study was to test natural and synthetic molecules for repellent activity against ticks in spatial, contact and human fingertip bioassays.
The efficacy of essential oils and naturally derived compounds as repellents to Am. americanum nymphs was compared in three different bioassays: contact, spatial and fingertip repellent bioassays.
Concentration response curves after contact exposure to 1R-trans-chrysanthemic acid (TCA) indicated a 5.6 μg/cm
concentration required to repel 50% of ticks (RC
), which was five- and sevenfold more active than DEET and nootkatone, respectively. For contact repellency, the rank order of repellency at 50 μg/cm
for natural oils was clove > geranium > oregano > cedarwood > thyme > amyris > patchouli > citronella > juniper berry > peppermint > cassia. For spatial bioassays, TCA was approximately twofold more active than DEET and nootkatone at 50 μg/cm
but was not significantly different at 10 μg/cm
. In spatial assays, thyme and cassia were the most active compounds tested with 100% and 80% ticks repelled within 15 min of exposure respectively and was approximately twofold more effective than DEET at the same concentration. To translate these non-host assays to efficacy when used on the human host, we quantified repellency using a finger-climbing assay. TCA, nootkatone and DEET were equally effective in the fingertip assay, and patchouli oil was the only natural oil that significantly repelled ticks.
The differences in repellent potency based on the assay type suggests that the ability to discover active tick repellents suitable for development may be more complicated than with other arthropod species; furthermore, the field delivery mechanism must be considered early in development to ensure translation to field efficacy. TCA, which is naturally derived, is a promising candidate for a tick repellent that has comparable repellency to commercialized tick repellents.
The nuclear receptor superfamily is composed of transcription factors that positively and negatively regulate gene expression in response to the binding of a diverse array of lipid-derived hormones ...and metabolites. Intense efforts are currently being directed at defining the biological roles and mechanisms of action of liver X receptors (LXRs) and peroxisome proliferator-activated receptors (PPARs). LXRs have been found to play essential roles in the regulation of whole body cholesterol absorption and excretion, in the efflux of cholesterol from peripheral cells, and in the biosynthesis and metabolism of very low density lipoproteins. PPARs have been found to regulate diverse aspects of lipid metabolism, including fatty acid oxidation, fat cell development, lipoprotein metabolism, and glucose homeostasis. Intervention studies indicate that activation of PPARα, PPARγ, and LXRs by specific synthetic ligands can inhibit the development of atherosclerosis in animal models.
Here, we review recent studies that provide new insights into the mechanisms by which these subclasses of nuclear receptors act to systemically influence lipid and glucose metabolism and regulate gene expression within the artery wall.
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