Translocated microbiome composition determines immunological outcome in treated HIV infection.

The impact of the microbiome on HIV disease is widely acknowledged although the mechanisms downstream of fluctuations in microbial composition remain speculative. We detected rapid, dynamic changes in translocated microbial constituents during two years after cART initiation. An unbiased systems biology approach revealed two distinct pathways driven by changes in the abundance ratio of Serratia to other bacterial genera. Increased CD4 T cell numbers over the first year were associated with high Serratia abundance, pro-inflammatory innate cytokines, and metabolites that drive Th17 gene expression signatures and restoration of mucosal integrity. Subsequently, decreased Serratia abundance and downregulation of innate cytokines allowed re-establishment of systemic T cell homeostasis promoting restoration of Th1 and Th2 gene expression signatures. Analyses of three other geographically distinct cohorts of treated HIV infection established a more generalized principle that changes in diversity and composition of translocated microbial species influence systemic inflammation and consequently CD4 T cell recovery.

Passive Transfer of Vaccine-Elicited Antibodies Protects against SIV in Rhesus Macaques.

Several HIV-1 and SIV vaccine candidates have shown partial protection against viral challenges in rhesus macaques. However, the protective efficacy of vaccine-elicited polyclonal antibodies has not previously been demonstrated in adoptive transfer studies in nonhuman primates. In this study, we show that passive transfer of purified antibodies from vaccinated macaques can protect naive animals against SIVmac251 challenges. We vaccinated 30 rhesus macaques with Ad26-SIV Env/Gag/Pol and SIV Env gp140 protein vaccines and assessed the induction of antibody responses and a putative protective signature. This signature included multiple antibody functions and correlated with upregulation of interferon pathways in vaccinated animals. Adoptive transfer of purified immunoglobulin G (IgG) from the vaccinated animals with the most robust protective signatures provided partial protection against SIVmac251 challenges in naive recipient rhesus macaques. These data demonstrate the protective efficacy of purified vaccine-elicited antiviral antibodies in this model, even in the absence of virus neutralization.

The transcription factor CREB1 is a mechanistic driver of immunogenicity and reduced HIV-1 acquisition following ALVAC vaccination.

Development of effective human immunodeficiency virus 1 (HIV-1) vaccines requires synergy between innate and adaptive immune cells. Here we show that induction of the transcription factor CREB1 and its target genes by the recombinant canarypox vector ALVAC + Alum augments immunogenicity in non-human primates (NHPs) and predicts reduced HIV-1 acquisition in the RV144 trial. These target genes include those encoding cytokines/chemokines associated with heightened protection from simian immunodeficiency virus challenge in NHPs. Expression of CREB1 target genes probably results from direct cGAMP (STING agonist)-modulated p-CREB1 activity that drives the recruitment of CD4+ T cells and B cells to the site of antigen presentation. Importantly, unlike NHPs immunized with ALVAC + Alum, those immunized with ALVAC + MF59, the regimen in the HVTN702 trial that showed no protection from HIV infection, exhibited significantly reduced CREB1 target gene expression. Our integrated systems biology approach has validated CREB1 as a critical driver of vaccine efficacy and highlights that adjuvants that trigger CREB1 signaling may be critical for efficacious HIV-1 vaccines.

CD8+ T cells promote HIV latency by remodeling CD4+ T cell metabolism to enhance their survival, quiescence, and stemness.

HIV infection persists during antiretroviral therapy (ART) due to a reservoir of latently infected cells that harbor replication-competent virus and evade immunity. Previous ex vivo studies suggested that CD8+ T cells from people with HIV may suppress HIV expression via non-cytolytic mechanisms, but the mechanisms responsible for this effect remain unclear. Here, we used a primary cell-based in vitro latency model and demonstrated that co-culture of autologous activated CD8+ T cells with HIV-infected memory CD4+ T cells promoted specific changes in metabolic and/or signaling pathways resulting in increased CD4+ T cell survival, quiescence, and stemness. Collectively, these pathways negatively regulated HIV expression and ultimately promoted the establishment of latency. As shown previously, we observed that macrophages, but not B cells, promoted latency in CD4+ T cells. The identification of CD8-specific mechanisms of pro-latency activity may favor the development of approaches to eliminate the viral reservoir in people with HIV.

A network comprising ELONGATED HYPOCOTYL5, microRNA397b, and auxin-associated factors regulates root hair growth in Arabidopsis.

ELONGATED HYPOCOTYL 5 (HY5) is a major light-associated transcription factor involved in plant growth and development. In Arabidopsis (Arabidopsis thaliana), the role of HY5 is very well-defined in regulating primary root growth and lateral root formation; however, information regarding its role in root hair development is still lacking, and little is known about the genetic pathways regulating this process. In this study, we investigated the role of HY5 and its associated components in root hair development. Detailed analysis of root hair phenotype in wild-type (WT) and light signaling mutants in light and dark conditions revealed the importance of light-dependent HY5-mediated root hair initiation. Altered auxin levels in the root apex of the hy5 mutant and interaction of HY5 with promoters of root hair developmental genes were responsible for differential expression of root hair developmental genes and phenotype in the hy5 mutant. The partial complementation of root hair in the hy5 mutant after external supplementation of auxin and regaining of root hair in PIN-FORMED 2 (pin2) and PIN-FORMED 2 (pin3) mutants after grafting suggested that the auxin-mediated root hair development pathway requires HY5. Furthermore, miR397b overexpression (miR397bOX) and CRISPR/Cas9-based mutants (miR397bCR) indicated miR397b targets genes encoding Reduced Residual Arabinose (RRA1/RRA2), which in turn regulate root hair growth. The regulation of the miR397b- (RRA1/RRA2) module by HY5 demonstrated its indirect role by targeting root hair cell wall genes. Together, this study demonstrated that HY5 controls root hair development by integrating auxin signalling and other miRNA-mediated pathways.

Local symmetry breaking drives picosecond spin domain formation in polycrystalline halide perovskite films.

Photoinduced spin-charge interconversion in semiconductors with spin-orbit coupling could provide a route to optically addressable spintronics without the use of external magnetic fields. However, in structurally disordered polycrystalline semiconductors, which are being widely explored for device applications, the presence and role of spin-associated charge currents remains unclear. Here, using femtosecond circular-polarization-resolved pump-probe microscopy on polycrystalline halide perovskite thin films, we observe the photoinduced ultrafast formation of spin domains on the micrometre scale formed through lateral spin currents. Micrometre-scale variations in the intensity of optical second-harmonic generation and vertical piezoresponse suggest that the spin-domain formation is driven by the presence of strong local inversion symmetry breaking via structural disorder. We propose that this leads to spatially varying Rashba-like spin textures that drive spin-momentum-locked currents, leading to local spin accumulation. Ultrafast spin-domain formation in polycrystalline halide perovskite films provides an optically addressable platform for nanoscale spin-device physics.

Human complete NFAT1 deficiency causes a triad of joint contractures, osteochondromas, and B-cell malignancy.

The discovery of humans with monogenic disorders has a rich history of generating new insights into biology. Here we report the first human identified with complete deficiency of nuclear factor of activated T cells 1 (NFAT1). NFAT1, encoded by NFATC2, mediates calcium-calcineurin signals that drive cell activation, proliferation, and survival. The patient is homozygous for a damaging germline NFATC2 variant (c.2023_2026delTACC; p.Tyr675Thrfs∗18) and presented with joint contractures, osteochondromas, and recurrent B-cell lymphoma. Absence of NFAT1 protein in chondrocytes caused enrichment in prosurvival and inflammatory genes. Systematic single-cell-omic analyses in PBMCs revealed an environment that promotes lymphomagenesis with accumulation of naïve B cells (enriched for oncogenic signatures MYC and JAK1), exhausted CD4+ T cells, impaired T follicular helper cells, and aberrant CD8+ T cells. This work highlights the pleiotropic role of human NFAT1, will empower the diagnosis of additional patients with NFAT1 deficiency, and further defines the detrimental effects associated with long-term use of calcineurin inhibitors.

Diagnostic accuracy of autofluorescence-Raman microspectroscopy for surgical margin assessment during Mohs micrographic surgery of basal cell carcinoma.

BACKGROUND: Autofluorescence (AF)-Raman microspectroscopy is a technology that can detect residual basal cell carcinoma (BCC) on the resection margin of fresh, surgically excised tissue specimens. The technology does not require tissue fixation, staining, labelling or sectioning, and provides quantitative diagnosis maps of the surgical margins in 30 min. OBJECTIVES: To determine the accuracy of the AF-Raman instrument in detecting incomplete BCC excisions during Mohs micrographic surgery (MMS), using histology as the reference standard. METHODS: Skin layers from 130 patients undergoing MMS at the Nottingham University Hospitals NHS Trust (September 2022-July 2023) were investigated with the AF-Raman instrument. The layers were measured when fresh, immediately after excision. The AF-Raman results and the intraoperative assessment by Mohs surgeons were compared with a postoperative consensus-derived reference produced by three dermatopathologists. The sensitivity, specificity, and positive and negative predictive values were calculated. The study was registered with ClinicalTrials.gov (NCT03482622). RESULTS: AF-Raman analysis was successfully completed for 125 of 130 layers and, on average, covered 91% of the specimen surface area, with the lowest surface area covered being 87% for the eyelid and the highest being 94% for forehead specimens. The AF-Raman instrument identified positive margins in 24 of 36 BCC-positive cases [67% sensitivity, 95% confidence interval (CI) 49-82] and negative margins in 65 of 89 BCC-negative cases (73% specificity, 95% CI 63-82). Only one of 12 false-negative cases was caused by misclassification by the AF-Raman algorithm. The other 11 false-negatives cases were a result of no valid Raman signal being recorded at the location of the residual BCC due to either occlusion by blood or poor contact between tissue and the cassette window. The intraoperative diagnosis by Mohs surgeons identified positive margins in 31 of 36 BCC-positive cases (86% sensitivity, 95% CI 70-95) and negative margins in 79 of 89 BCC-negative cases (89% specificity, 95% CI 81-95). CONCLUSIONS: The AF-Raman instrument has the potential to provide intraoperative microscopic assessment of surgical margins in BCC surgery. Further improvements are required for tissue processing, to ensure complete coverage of the surgical specimens.

Basal cell carcinoma (BCC) is one of the most common human cancers, occurring mostly on the face and neck. Most BCCs are treated by cutting them out under local anaesthetic. This is routinely done in a hospital by a dermatologist or plastic surgeon. Surgery aims to remove all the cancer leaving the smallest scar possible, but it is often difficult to know how much normal skin to remove. Results from the laboratory often take 1 to 2 weeks to show if the cancer is clear. A technique called 'Mohs' (micrographic surgery) is recommended for these 'high-risk' BCCs. Mohs surgery removes thin layers of skin and investigates them under a microscope while the patient is still in the hospital. This is repeated until all the layers are clear of cancer. Because of the patchy availability of Mohs surgery, many patients with high-risk BCCs are treated by traditional methods that may not be as good as Mohs. We have developed an instrument that scans layers of skin and can quickly detect BCC. The instrument allows surgeons to check each removed skin layer for cancer cells to decide if more layers need to be removed. In this study, the instrument was tested on skin tissue layers from 130 patients who had Mohs surgery at the Nottingham Treatment Centre. The results showed that the instrument can measure skin layers in approximately 30 minutes and identify BCC with a similar accuracy to a Mohs surgeon, but only when the skin layers are prepared properly. With future improvements, the technology might be used to guide Mohs surgery or help surgeons in centres that do not have access to Mohs surgery.

Small Donors, Big Impact: Optimizing Organ Utilization in Simultaneous Pancreas and Kidney Transplantation From Extra Small Pediatric Donors.

INTRODUCTION: Simultaneous pancreas-kidney transplantation (SPK) is the preferred treatment for individuals with type-1 diabetes and end-stage renal disease. However, a limited supply of "Ideal Pancreas Donors" contributed to a growing disparity between available organs and recipients. Even though SPK outcomes from pediatric donors match those from adult donors, unclear guidelines on minimum age and weight criteria for extra small pediatric pancreas donors lead to hesitancy among several transplant centers to utilize these grafts due to concerns about inadequate islet mass, technical challenges, and increased risk of allograft thrombosis. METHODS: This report details the successful outcomes of SPK transplantations performed at the study center between December 2021 and January 2024, using four extra small pediatric brain-dead donors (ESPDs). Each donor was aged ≤5 years and weighed <20 kg. RESULTS: All SPK recipients achieved immediate posttransplant euglycemia without requiring insulin. None of the recipients experienced graft pancreatitis, graft thrombosis, allograft rejection, or required re-exploration. During a 5-27-month follow-up period, all ESPD recipients maintained optimal graft function, as evidenced by normal glucose tolerance tests and HbA1c (4.9%-5.2%), with 100% graft and patient survival. CONCLUSION: This report examines the usage of ESPDs in SPK transplantation, highlighting their potential to expand the donor pool and reduce wait times in areas with scarce deceased organ donations, thereby increasing the number of available organs for transplantation with acceptable outcomes. Revising donor selection guidelines to reflect the diverse risk-benefit profiles of waitlisted individuals is crucial to addressing geographical disparities and reducing organ discard rates.

Design of substituted tetrahydrofuran derivatives for HIV-1 protease inhibitors: synthesis, biological evaluation, and X-ray structural studies.

Substituted tetrahydrofuran derivatives were designed and synthesized to serve as the P2 ligand for a series of potent HIV-1 protease inhibitors. Both enantiomers of the tetrahydrofuran derivatives were synthesized stereoselectivity in optically active forms using lipase-PS catalyzed enzymatic resolution as the key step. These tetrahydrofuran derivatives are designed to promote hydrogen bonding and van der Waals interactions with the backbone atoms in the S2 subsite of the HIV-1 protease active site. Several inhibitors displayed very potent HIV-1 protease inhibitory activity. A high-resolution X-ray crystal structure of an inhibitor-bound HIV-1 protease provided important insight into the ligand binding site interactions in the active site.

Gut mycobiome dysbiosis after sepsis and trauma.

BACKGROUND: Sepsis and trauma are known to disrupt gut bacterial microbiome communities, but the impacts and perturbations in the fungal (mycobiome) community after severe infection or injury, particularly in patients experiencing chronic critical illness (CCI), remain unstudied. METHODS: We assess persistence of the gut mycobiome perturbation (dysbiosis) in patients experiencing CCI following sepsis or trauma for up to two-to-three weeks after intensive care unit hospitalization. RESULTS: We show that the dysbiotic mycobiome arrays shift toward a pathobiome state, which is more susceptible to infection, in CCI patients compared to age-matched healthy subjects. The fungal community in CCI patients is largely dominated by Candida spp; while, the commensal fungal species are depleted. Additionally, these myco-pathobiome arrays correlate with alterations in micro-ecological niche involving specific gut bacteria and gut-blood metabolites. CONCLUSIONS: The findings reveal the persistence of mycobiome dysbiosis in both sepsis and trauma settings, even up to two weeks post-sepsis and trauma, highlighting the need to assess and address the increased risk of fungal infections in CCI patients.

Accelerated full-thickness skin wound tissue regeneration by self-crosslinked chitosan hydrogel films reinforced by oxidized CNC-AgNPs stabilized Pickering emulsion for quercetin delivery.

BACKGROUND: The non-toxic self-crosslinked hydrogel films designed from biocompatible materials allow for controlled drug release and have gathered remarkable attention from healthcare professionals as wound dressing materials. Thus, in the current study the chitosan (CS) film is infused with oil-in-water Pickering emulsion (PE) loaded with bioactive compound quercetin (Qu) and stabilized by dialdehyde cellulose nanocrystal-silver nanoparticles (DCNC-AgNPs). The DCNC-AgNPs play a dual role in stabilizing PE and are involved in the self-crosslinking with CS films. Also, this film could combine the advantage of the controlled release and synergistic wound-healing effect of Qu and AgNPs. RESULTS: The DCNC-AgNPs were synthesized using sodium periodate oxidation of CNC. The DCNC-AgNPs were used to stabilize oil-in-water PE loaded with Qu in its oil phase by high speed homogenization. Stable PEs were prepared by 20% v/v oil: water ratio with maximum encapsulation of Qu in the oil phase. The Qu-loaded PE was then added to CS solution (50% v/v) to prepare self-crosslinked films (CS-PE-Qu). After grafting CS films with PE, the surface and cross-sectional SEM images show an inter-penetrated network within the matrix between DCNC and CS due to the formation of a Schiff base bond between the reactive aldehyde groups of DCNC-AgNPs and amino groups of CS. Further, the addition of glycerol influenced the extensibility, swelling ratio, and drug release of the films. The fabricated CS-PE-Qu films were analyzed for their wound healing and tissue regeneration potential using cell scratch assay and full-thickness excisional skin wound model in mice. The as-fabricated CS-PE-Qu films showed great biocompatibility, increased HaCat cell migration, and promoted collagen synthesis in HDFa cells. In addition, the CS-PE-Qu films exhibited non-hemolysis and improved wound closure rate in mice compared to CS, CS-Qu, and CS-blank PE. The H&E staining of the wounded skin tissue indicated the wounded tissue regeneration in CS-PE-Qu films treated mice. CONCLUSION: Results obtained here confirm the wound healing benefits of CS-PE-Qu films and project them as promising biocompatible material and well suited for full-thickness wound healing in clinical applications.

An Enzymatic Route to the Synthesis of Tricyclic Fused Hexahydrofuranofuran P2-Ligand for a Series of Highly Potent HIV-1 Protease Inhibitors.

We describe a stereoselective synthesis of an optically active (1R, 3aS, 5R, 6S, 7aR)-octahydro-1,6-epoxy-isobenzo-furan-5-ol derivative. This stereochemically defined heterocycle serves as a high-affinity ligand for a variety of HIV-1 protease inhibitors. The key synthetic steps involve a highly enantioselective enzymatic desymmetrization of meso-1,2(dihydroxymethyl)cyclohex-4-ene and conversion of the resulting optically active alcohol to a methoxy hexahydroisobenzofuran derivative. A substrate controlled stereoselective dihydroxylation afforded syn-1,2-diols. Oxidation of diol provided the substituted 1,2-diketone and L-Selectride reduction provided the corresponding inverted syn-1,2-diols. Acid catalyzed cyclization furnished the ligand alcohol in optically active form.

Complementary and alternative medicine use among pregnant women attending antenatal clinic: a point to ponder.

OBJECTIVES: Complementary and Alternative Medicine (CAM) is a group of diverse medical and healthcare systems, practices, and products that are not generally considered part of conventional medicine. Pregnant women are vulnerable to adverse effects of medicines, especially during the first trimester. Though it is advised to avoid unnecessary intake of medicine during pregnancy, CAM use is widespread. METHODS: A cross-sectional questionnaire-based study was conducted on 120 pregnant women attending the antenatal clinic of a tertiary-care teaching hospital in Udaipur district of Southern Rajasthan, India. Women of age 18 years and above were surveyed between July 2022 to December 2023 by convenient sampling strategy and data were entered in a pretested and pre-validated questionnaire. The data were analyzed using descriptive statistics, the Chi-square test was applied to compare CAM use among different demographic categories and a p-value less than 0.05 was considered statistically significant. RESULTS: Out of 120 participants, 58 (48.33 %) were using CAM therapy. Out of 58 users, 44 (75.86 %) were using herbal & traditional medicines. Twenty (34.48 %) were using CAM for a healthy baby, 18 (31.03 %) for easy delivery and 17 (29.31 %) for boosting immunity. Forty (68.96 %) participants started CAM on the advice of a relative/friend. Fifty six (46.67 %) participants believe that CAM therapy cannot cause adverse effects on the in utero child, while 32 (26.67 %) believe that CAM and modern medicines don't interact. CONCLUSIONS: CAM use among pregnant women is substantial. There is a need to raise awareness among the healthcare professionals and pregnant women regarding possible adverse effects and drug-drug interactions with CAM use.

Soluble Diphenylhexatriene Dimers for Intramolecular Singlet Fission with High Triplet Energy.

Intramolecular singlet fission (iSF) facilitates single-molecule exciton multiplication, converting an excited singlet state to a pair of triplet states within a single molecule. A critical parameter in determining the feasibility of SF-enhanced photovoltaic designs is the triplet energy; many existing iSF materials have triplet energies too low for efficient transfer to silicon via a photon multiplier scheme. In this work, a series of six novel dimers based upon the high-triplet-energy, SF-active chromophore, 1,6-diphenyl-1,3,5-hexatriene (DPH) [E(T1) ∼ 1.5 eV], were designed, synthesized, and characterized. Transient absorption spectroscopy and fluorescence lifetime studies reveal that five of the dimers display iSF activity, with time constants for singlet fission varying between 7 ± 2 ps and 2.2 ± 0.2 ns and a high triplet yield of 163 ± 63% in the best-performing dimer. A strong dependence of the rate of fission on the coupling geometry is demonstrated. For optimized iSF behavior, close spatial proximity and minimal through-bond communication are found to be crucial for balancing the rate of SF against the reverse recombination process.

Scedosporium Infection in Recipients of Kidney Transplants from Deceased Near-Drowning Donor.

Scedosporium aurianticum infection developed in 2 recipients of kidney transplants in India, acquired from the same deceased near-drowning donor. Given the substantial risk for death associated with Scedosporium infection among solid-organ transplant recipients, safety protocols for organ transplantation from nearly drowned donors should be thoroughly revaluated and refined.

TCA cycle remodeling drives proinflammatory signaling in humans with pulmonary tuberculosis.

The metabolic signaling pathways that drive pathologic tissue inflammation and damage in humans with pulmonary tuberculosis (TB) are not well understood. Using combined methods in plasma high-resolution metabolomics, lipidomics and cytokine profiling from a multicohort study of humans with pulmonary TB disease, we discovered that IL-1ß-mediated inflammatory signaling was closely associated with TCA cycle remodeling, characterized by accumulation of the proinflammatory metabolite succinate and decreased concentrations of the anti-inflammatory metabolite itaconate. This inflammatory metabolic response was particularly active in persons with multidrug-resistant (MDR)-TB that received at least 2 months of ineffective treatment and was only reversed after 1 year of appropriate anti-TB chemotherapy. Both succinate and IL-1ß were significantly associated with proinflammatory lipid signaling, including increases in the products of phospholipase A2, increased arachidonic acid formation, and metabolism of arachidonic acid to proinflammatory eicosanoids. Together, these results indicate that decreased itaconate and accumulation of succinate and other TCA cycle intermediates is associated with IL-1ß-mediated proinflammatory eicosanoid signaling in pulmonary TB disease. These findings support host metabolic remodeling as a key driver of pathologic inflammation in human TB disease.

MicroRNA858a, its encoded peptide, and phytosulfokine regulate Arabidopsis growth and development.

Small molecules, such as peptides and miRNAs, are crucial regulators of plant growth. Here, we show the importance of cross-talk between miPEP858a (microRNA858a-encoded peptide)/miR858a and phytosulfokine (PSK4) in regulating plant growth and development in Arabidopsis (Arabidopsis thaliana). Genome-wide expression analysis suggested modulated expression of PSK4 in miR858a mutants and miR858a-overexpressing (miR858aOX) plants. The silencing of PSK4 in miR858aOX plants compromised growth, whereas overexpression of PSK4 in the miR858a mutant rescued the developmental defects. The exogenous application of synthetic PSK4 further complemented the plant development in mutant plants. Exogenous treatment of synthetic miPEP858a in the PSK4 mutant led to clathrin-mediated internalization of the peptide; however, it did not enhance growth as is the case in wild-type plants. We also demonstrated that MYB3 is an important molecular component participating in the miPEP858a/miR858a-PSK4 module. Finally, our work highlights the signaling between miR858a/miPEP858a-MYB3-PSK4 in modulating the expression of key elements involved in auxin responses, leading to the regulation of growth.

Resolution of inflammation via RvD1/FPR2 signaling mitigates Nox2 activation and ferroptosis of macrophages in experimental abdominal aortic aneurysms.

Abdominal aortic aneurysm (AAA) formation is characterized by inflammation, leukocyte infiltration, and vascular remodeling. Resolvin D1 (RvD1) is derived from ω-3 polyunsaturated fatty acids and is involved in the resolution phase of chronic inflammatory diseases. The aim of this study was to decipher the protective role of RvD1 via formyl peptide receptor 2 (FPR2) receptor signaling in attenuating abdominal aortic aneurysms (AAA). The elastase-treatment model of AAA in C57BL/6 (WT) mice and human AAA tissue was used to confirm our hypotheses. Elastase-treated FPR2-/- mice had a significant increase in aortic diameter, proinflammatory cytokine production, immune cell infiltration (macrophages and neutrophils), elastic fiber disruption, and decrease in smooth muscle cell α-actin expression compared to elastase-treated WT mice. RvD1 treatment attenuated AAA formation, aortic inflammation, and vascular remodeling in WT mice, but not in FPR2-/- mice. Importantly, human AAA tissue demonstrated significantly decreased FPR2 mRNA expression compared to non-aneurysm human aortas. Mechanistically, RvD1/FPR2 signaling mitigated p47phox phosphorylation and prevented hallmarks of ferroptosis, such as lipid peroxidation and Nrf2 translocation, thereby attenuating HMGB1 secretion. Collectively, this study demonstrates RvD1-mediated immunomodulation of FPR2 signaling on macrophages to mitigate ferroptosis and HMGB1 release, leading to resolution of aortic inflammation and remodeling during AAA pathogenesis.

Graphene quantum dot doped viscoelastic lyotropic liquid crystal nanocolloids for antibacterial applications.

Graphene quantum dots (GQDs) are prepared and characterized via X-ray diffraction (XRD), UV-Visible spectroscopy, atomic force microscopy (AFM), transmission electron microscopy (TEM) and photoluminescence (PL). GQDs are doped (5 mg and 10 mg) in the lyotropic liquid crystalline (LLC) lamellar and hexagonal phases to prepare GQD/LLC nanocolloids. Polarizing optical microscopy and X-ray diffraction measurement reveals that GQDs do not affect the lamellar and hexagonal LLC structures and may organize on their interface. Pure LLC phases and nanocolloids are studied for steady and dynamic rheological behavior. LLC phases and GQD/LLC nanocolloids possess shear thinning and frequency dependent liquid viscoelastic behavior. A complex moduli study of LLCs and GQD/LLC nanocolloids is carried out which indicates the gel to viscous transition in LLCs and GQD/LLC nanocolloids as a function of frequency. LLC phases and GQD/LLC nanocolloids are tested for antibacterial activity against Listeria ivanovii. The effect of surfactant concentration, LLC phase geometry and GQD concentration has been studied and discussed. A probable mechanism for the strong antimicrobial activity of LLCs and GQD/LLC nanocolloids is presented considering intermolecular interactions. The viscoelastic behavior and strong antibacterial activity (inhibition zone 49.2 mm) of LLCs and GQD/LLC nanocolloids make them valuable candidates for lubrication, cleaning, cosmetics and pharmaceutical applications.