Synthesis of BODIPY FL-tethered ridaifen-B, RID-B-BODIPY, and its localization in cancer cells.

We synthesized ridaifen-B boron dipyrromethene () using 2-methyl-6-nitro benzoic anhydride (MNBA)-mediated dehydration condensation reaction between amino alkyl-tethered RID and BODIPY FL. Comparative experiments between dicyclohexylcarbodiimide (DCC) and MNBA for their coupling reactions demonstrated that MNBA is an effective condensation reagent for amines and BODIPY FL. A cell staining study with showed intracellular localization of BODIPY FL fluorescence, attributed to the structure, indicating the successful development of a tool for analyzing intracellular molecular behavior efficiently.

Polygenic risk score portability for common diseases across genetically diverse populations.

Background: Polygenic risk scores (PRS) derived from European individuals have reduced portability across global populations, limiting their clinical implementation at worldwide scale. Here, we investigate the performance of a wide range of PRS models across four ancestry groups (Africans, Europeans, East Asians, and South Asians) for 14 conditions of high-medical interest.

Methods: To select the best-performing model per trait, we first compared PRS performances for publicly available scores, and constructed new models using different methods (LDpred2, PRS-CSx and SNPnet).

Repeated Omicron exposures redirect SARS-CoV-2-specific memory B cell evolution toward the latest variants.

Immunological imprinting by ancestral SARS-CoV-2 strains is thought to impede the robust induction of Omicron-specific humoral responses by Omicron-based booster vaccines. Here, we analyzed the specificity and neutralization activity of memory B (B) cells after repeated BA.5 exposure in individuals previously imprinted by ancestral strain-based mRNA vaccines.

subsp. YRC3780 modifies function of mesenteric lymph node dendritic cells to modulate the balance of T cell differentiation inducing regulatory T cells.

Introduction: The intestinal immune system plays a pivotal role in the induction of immune responses against food. In the case of T cell response, dendritic cells (DCs) are especially important. However, the regulation of immune responses to food by intestinal DCs has been poorly described.

CD62L expression marks SARS-CoV-2 memory B cell subset with preference for neutralizing epitopes.

Severe acute respiratory syndrome coronavirus 2-neutralizing antibodies primarily target the spike receptor binding domain (RBD). However, B cell antigen receptors (BCRs) on RBD-binding memory B (B) cells have variation in the neutralizing activities. Here, by combining single B cell profiling with antibody functional assessment, we dissected the phenotype of B cell harboring the potently neutralizing antibodies in coronavirus disease 2019 (COVID-19)-convalescent individuals.

Orally administered OLL2712 decreased intestinal permeability, especially in the ileum: Ingested lactic acid bacteria alleviated obesity-induced inflammation by collaborating with gut microbiota.

Introduction: Chronic inflammation caused by dietary obesity has been considered to induce lifestyle-related diseases and functional ingredients with anti-inflammatory effects are attracting attention. Although multiple studies on obesity had proved the anti-inflammatory effects of ingestion of lactic acid bacteria (LAB) and other functional ingredients on adipose tissue, the precise effects on the intestine, especially on the individual intestinal segments have not been made clear. In this study, we elucidated the mechanisms of (basonym: ) OLL2712 in suppressing obesity-induced inflammation using high fat diet (HFD)-fed mice obesity model.

Immune responses related to the immunogenicity and reactogenicity of COVID-19 mRNA vaccines.

Vaccination for the prevention of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection is considered the most promising approach to control the pandemic of coronavirus disease 2019 (COVID-19). Although various COVID-19 vaccines have been developed worldwide using several modalities, the vaccines that have shown the highest efficacy to date are mRNA vaccines. Despite their extensive usage, the mechanisms that stimulate the immune responses associated with their immunogenicity and reactogenicity remain largely unknown.

Validating and automating learning of cardiometabolic polygenic risk scores from direct-to-consumer genetic and phenotypic data: implications for scaling precision health research.

Introduction: A major challenge to enabling precision health at a global scale is the bias between those who enroll in state sponsored genomic research and those suffering from chronic disease. More than 30 million people have been genotyped by direct-to-consumer (DTC) companies such as 23andMe, Ancestry DNA, and MyHeritage, providing a potential mechanism for democratizing access to medical interventions and thus catalyzing improvements in patient outcomes as the cost of data acquisition drops. However, much of these data are sequestered in the initial provider network, without the ability for the scientific community to either access or validate.

SARS-CoV-2-specific CD4 T cell longevity correlates with Th17-like phenotype.

Determinants of memory T cell longevity following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remain unknown. In addition, phenotypes associated with memory T cell longevity, antibody titers, and disease severity are incompletely understood. Here, we longitudinally analyzed SARS-CoV-2-specific T cell and antibody responses of a unique cohort with similar numbers of mild, moderate, and severe coronavirus disease 2019 cases.

β-elemene regulates M1-M2 macrophage balance through the ERK/JNK/P38 MAPK signaling pathway.

Macrophages are classified into classically activated M1 macrophages and alternatively activated M2 macrophages, and the two phenotypes of macrophages are present during the development of various chronic diseases, including obesity-induced inflammation. In the present study, β-elemene, which is contained in various plant substances, is predicted to treat high-fat diet (HFD)-induced macrophage dysfunction based on the Gene Expression Omnibus (GEO) database and experimental validation. β-elemene impacts the imbalance of M1-M2 macrophages by regulating pro-inflammatory cytokines in mouse white adipose tissue both in vitro and in vivo.

Distinct immune cell dynamics correlate with the immunogenicity and reactogenicity of SARS-CoV-2 mRNA vaccine.

Two doses of Pfizer/BioNTech BNT162b2 mRNA vaccine elicit robust severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-neutralizing antibodies with frequent adverse events. Here, by applying a high-dimensional immune profiling on 92 vaccinees, we identify six vaccine-induced immune dynamics that correlate with the amounts of neutralizing antibodies, the severity of adverse events, or both. The early dynamics of natural killer (NK)/monocyte subsets (CD16 NK cells, CD56 NK cells, and non-classical monocytes), dendritic cell (DC) subsets (DC3s and CD11c Axl Siglec-6 [AS]-DCs), and NKT-like cells are revealed as the distinct cell correlates for neutralizing-antibody titers, severity of adverse events, and both, respectively.

SARS-CoV-2 Omicron-neutralizing memory B cells are elicited by two doses of BNT162b2 mRNA vaccine.

Multiple SARS-CoV-2 variants have mutations in the spike receptor binding domain (RBD) with potential to evade neutralizing antibody. In particular, the Beta and Omicron variants escape from antibody neutralizing activity in those who received two doses of BNT162b2 mRNA vaccine. Nonetheless, boosting with a third vaccine dose or by breakthrough infection improves the overall breadth of the neutralizing antibodies, but the mechanism remains unclear.

β-Elemene Suppresses Obesity-Induced Imbalance in the Microbiota-Gut-Brain Axis.

As a kind of metabolically triggered inflammation, obesity influences the interplay between the central nervous system and the enteral environment. The present study showed that β-elemene, which is contained in various plant substances, had effects on recovering the changes in metabolites occurring in high-fat diet (HFD)-induced obese C57BL/6 male mice brains, especially in the prefrontal cortex (PFC) and hippocampus (HIP). β-elemene also partially reversed HFD-induced changes in the composition and contents of mouse gut bacteria.

A technique for creating an experimental type Ia endoleak model in the thoracic aorta of swine.

Purpose: This study aimed to create an animal model of type Ia endoleak that creates persistent problems after thoracic endovascular aortic repair.

Materials And Methods: In six swine, thoracic aortic aneurysms were created using the harvested jugular vein. We created a type Ia endoleak using a composite stent-graft comprising the first stent-graft (reverse-tapered: thicker part, 16 mm; thinner part, 10 mm) and the second stent-graft (tapered: thicker part, 18-20 mm; thinner part, 16 mm).

Association of HLA-DRB1*09:01 with severe COVID-19.

HLA-A, -C, -B, and -DRB1 genotypes were analyzed in 178 Japanese COVID-19 patients to investigate the association of HLA with severe COVID-19. Analysis of 32 common HLA alleles at four loci revealed a significant association between HLA-DRB1*09:01 and severe COVID-19 (odds ratio [OR], 3.62; 95% CI, 1.

Reflected wave intensity increases based on aortic diameter after endovascular aortic therapy in a goat model.

Reflected wave increases after endovascular aortic repair (EVAR) in patients with aortic aneurysm. This affects the left ventricular (LV) diastolic function and leads to a poor prognosis. This study aimed to evaluate the relationship between increased reflected wave amplitude and aortic diameter after EVAR.

Outpatient Cardiac Rehabilitation Suppresses Deterioration of Renal Function in Patients ≥75 Years of Age With Heart Disease.

Background: This study investigated the effect of outpatient cardiac rehabilitation (OCR) and physical activity on the estimated glomerular filtration rate based on serum cystatin C (eGFRcys) in patients with heart disease (HD) aged ≥75 years.

Methods and results: This non-randomized prospective intervention study involved 136 patients (non-OCR group, n=66; OCR group, n=70), 55 of whom were aged ≥75 years (non-OCR group, n=29; OCR group, n=26). Renal function (eGFRcys) was evaluated at discharge and 3 months thereafter.

Intestinal regulatory T cell induction by β-elemene alleviates the formation of fat tissue-related inflammation.

The role of the intestinal immune system in the inhibition of fat tissue-related inflammation by dietary material is yet to be elucidated. Oral administration of β-elemene, contained in various foodstuffs, downregulated expressions of inflammatory cytokines and increased Foxp3CD4 T cells in adipose tissue of obese mice. However, β-elemene did not affect the inflammatory response of adipose tissue , suggesting that the inhibition observed was not due to direct interactions of adipose tissue with β-elemene.

Age-Dependent Decrease in the Induction of Regulatory T Cells Is Associated With Decreased Expression of RALDH2 in Mesenteric Lymph Node Dendritic Cells.

A decline in immune function with aging has been reported. Regulatory T cell (Treg) induction is known to decrease with age, and elucidating the underlying mechanism is important for preventing age-related diseases due to age-related chronic inflammation. In the intestine, dendritic cells (DCs) play an important role in inducing Tregs specific to oral antigens, and they efficiently induce Tregs via production of retinoic acid (RA), a vitamin A metabolite, catalyzed by the enzyme retinaldehyde dehydrogenase 2 (RALDH2).